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WO2024168183A1 - Long-term biostable thermoplastic compositions and medical devices containing the same - Google Patents

Long-term biostable thermoplastic compositions and medical devices containing the same Download PDF

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Publication number
WO2024168183A1
WO2024168183A1 PCT/US2024/015048 US2024015048W WO2024168183A1 WO 2024168183 A1 WO2024168183 A1 WO 2024168183A1 US 2024015048 W US2024015048 W US 2024015048W WO 2024168183 A1 WO2024168183 A1 WO 2024168183A1
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WIPO (PCT)
Prior art keywords
aspects
poly
group
isobutylene
formula
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
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PCT/US2024/015048
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French (fr)
Inventor
Shrojalkumer M. DESAI
Biswa P. DAS
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Edwards Lifesciences Corp
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Edwards Lifesciences Corp
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Publication of WO2024168183A1 publication Critical patent/WO2024168183A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/62—Polymers of compounds having carbon-to-carbon double bonds
    • C08G18/6204—Polymers of olefins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/24—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2412—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body with soft flexible valve members, e.g. tissue valves shaped like natural valves
    • A61F2/2418—Scaffolds therefor, e.g. support stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
    • C08G18/72—Polyisocyanates or polyisothiocyanates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/24—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2412—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body with soft flexible valve members, e.g. tissue valves shaped like natural valves
    • A61F2/2415—Manufacturing methods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2230/0002—Two-dimensional shapes, e.g. cross-sections
    • A61F2230/0028—Shapes in the form of latin or greek characters
    • A61F2230/0054—V-shaped
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0069—Sealing means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves

Definitions

  • most of the polymeric components for structural heart implants are in the form of coated or stand-alone films, i.e., as parts with high aspect ratio shapes.
  • the major requirements of these films are biostability, i.e., longevity against material degradation due to the reactions caused by in vivo environment; fatigue resistance as the device is subjected to the same movements as the part of the beating heart it is providing therapy; and specific requirements of flexibility, elasticity and softness of the film as a device component.
  • Some of the common implantable polymers belong to the polymer families of silicone rubber, fluoropolymers, polyethylenes, polypropylenes, polyacrylates, and standard polyurethanes, but none of them are promising candidates for the combined biostability, fatigue resistance and additional specific requirements for structural heart implants’ components.
  • the polyurethane family of polymers is the most interesting because of the variety of approaches by which the polyurethane properties can be tuned.
  • Polyisobutylene (PIB) based polyurethanes have been identified as polyurethanes with unprecedented chemical resistance. Polyurethanes, which comprise at least one PIB segment, are believed to possess enhanced biostability and biocompatibility as the PIB segment is highly resistant to in vivo degradation.
  • PIB polyurethane presents the risk of not meeting the in vivo environment longevity (> 20 years) and fatigue resistance (> 800 million cycles) required for film-shaped components of structural heart implants.
  • the challenge with PIB polyurethanes is the phase separation of hard segments that makes the material contain regions that are more susceptible to in vivo degradation.
  • polyurethane linkages still desire additional strength to meet the long-term biostability requirement of structural heart implant components.
  • further tunability of the PIB polyurethane may be required to meet the specific requirements depending on the type of film component.
  • a crosslinked polyurethane obtained by crosslinking a polyurethane having the formula: wherein a is from 1-10,000; b is from 1-10,000; c is from 0-500; [soft] represents a macrodiol segment comprising a poly(isobutylene) component; [DI] represents a diisocyante component; [CE] represents a chain extender component; [CC] represents a chain connector component, wherein one or more of [soft], [DI], [CE], and [CC] comprises a crosslinkable group.
  • the crosslinked polyurethane wherein the polyurethane has a molecular weight from 50,000 g/mol to 1,000,000 g/mol.
  • the polyurethane has a molecular weight that is from 100,000 g/mol to 300,000 g/mol.
  • the crosslinked polyurethane wherein the crosslinkable group comprises a carbon-carbon double bond, carbon-carbon triple bond, epoxide, carboxylic acid, activated carboxylic acids, a clickable group, or combination thereof.
  • the crosslinked polyurethane wherein the crosslinkable group comprises a carbon-carbon double bond.
  • the crosslinked polyurethane wherein the crosslinkable group comprises a terminal alkyne, azide, or combination thereof.
  • the crosslinked polyurethane wherein the crosslinkable group comprises an epoxide.
  • the crosslinked polyurethane wherein [soft] comprises a poly(alkenyl) component.
  • [soft] comprises a poly(1,3-butadiene), poly(2,3-dimethyl-1,3-butadiene), or poly(isoprene) component.
  • [015] is the crosslinked polyurethane, wherein [soft] comprises a poly(alkynyl) component.
  • the crosslinked polyurethane wherein [soft] comprises a poly(alkyl) component, wherein the poly(alkyl) is not polyisobutylene.
  • [soft] comprises a poly(ethylene) component.
  • [soft] comprises a poly(ethylene glycol) component.
  • the crosslinked polyurethane wherein [soft] comprises a poly(isobutylene-co- isoprene) component.
  • the crosslinked polyurethane wherein the poly(isobutylene-co-isoprene) component is a block copolymer.
  • the crosslinked polyurethane wherein the poly(isobutylene-co-isoprene) component is a random copolymer.
  • the crosslinked polyurethane wherein [soft] comprises a poly(isobutylene-co- isoprene) component, wherein the isobutylene portion is present in an amount from 1-99 wt.% relative to the isoprene portion.
  • [soft] comprises a poly(isobutylene-co- ethylene) component.
  • the crosslinked polyurethane wherein the poly(isobutylene-co-ethylene) component is a block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the crosslinked polyurethane wherein the poly(isobutylene-co-ethylene) component is a random copolymer with the poly(isobutylene) or poly(isobutylene-co- isoprene) portion.
  • the crosslinked polyurethane wherein [soft] comprises a poly(isobutylene-co- ethylene) component, wherein the poly(alkylene) portion is present in an amount of 1-99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • [soft] comprises a poly(isobutylene-co- ethylene-co-isoprene) component.
  • the crosslinked polyurethane wherein the poly(isobutylene-co-ethylene-co- isoprene) component is a block copolymer.
  • the crosslinked polyurethane wherein the poly(isobutylene-co-ethylene-co- isoprene) component is a random copolymer.
  • [soft] comprises a poly(meth)acrylate component.
  • crosslinked polyurethane wherein [soft] comprises a poly(meth)acrylate component, wherein the poly(meth)acrylate portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(meth)acrylate component comprises an oligomer derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec-butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof.
  • the poly(meth)acrylate component comprises an oligomer derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, but
  • the crosslinked polyurethane wherein [soft] comprises a poly(siloxane) component.
  • [soft] comprises a poly(siloxane) component in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene- co-isoprene) portion.
  • the crosslinked polyurethane wherein [soft] comprises a poly(dimethylsiloxane), a poly(vinyl-methylsiloxane), or a poly(divinylsiloxane) component.
  • [soft] comprises a polyethylene glycol component.
  • the crosslinked polyurethane wherein the polyethylene glycol component has a molecular weight (in Daltons) from 100-100,000, from 500-10,000, from 1,000-50,000, from 500-2,500, from 2,500-7,500, from 5,000-10,000, from 10,000-25,000, from 25,000-50,000, or from 50,000-100,000.
  • the crosslinked polyurethane wherein [soft] comprises an oligomer having the formula: -[-(A 1 ) d -(A 2 ) e -(A 3 ) f -(A 4 ) g -(A 5 ) h -(A 6 ) peg ]-, wherein A 1 is (isobutylene), and d is 1-10,000; A 2 is C 4-20 alkenyl, and e is 0-500; A 3 is C 4- 20alkynyl, and f is 0-500; A 4 is C2-20alkyl, and g is 0-10,000; A 5 is a siloxane, and h is 0- 10,000; A 6 is a polyethylene glycol, and peg is 0-10,000; wherein d, e, f, g, h, and peg represent the number of monomer units.
  • the crosslinked polyurethane wherein A 4 is ethylene or a mixture of (ethylene) and (propylene).
  • a 4 is ethylene or a mixture of (ethylene) and (propylene).
  • a 2 is (1,3-butadiene), (2,3-dimethyl-1,3- butadiene), (isoprene), or a combination thereof.
  • a 2 is (isoprene).
  • the crosslinked polyurethane wherein A 2 has the formula: .
  • a 5 is (dimethyl)siloxane.
  • the crosslinked polyurethane wherein A 3 and A 6 are absent.
  • crosslinked polyurethane wherein [soft] is an oligomer having the formula: -[isobutylenyl]i-[isoprenyl]m-[dimethylsiloxane]o-, or -[isobutylenyl] i -[isoprenyl] m -[ethylenyl] n -[ dimethylsiloxane] o -; wherein: i is 1-10,000; n is 1-10,000; m is 1-50; and o is 0-10,000.
  • the crosslinked polyurethane wherein [DI] includes segments of Formula (1): [Formula (1)], wherein the wavy lines represent points of attachment to any of [soft], [CE], or [CC], wherein R 1 is a saturated C 2-30 group.
  • R 1 has the formula:
  • the crosslinked polyurethane wherein R 2 has the formula: , .
  • [051] in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [DI] includes segments of Formula (3): [Formula (3)], wherein the wavy lines to any of [soft], [CE], or [CC], wherein R 3 is a C 6-30 aromatic group.
  • the crosslinked polyurethane wherein R 3 has the formula: or aspects, disclosed is the crosslinked polyurethane, wherein [CE] includes segments of Formula (4): [Formula (4)], wherein the wavy lines represent to [DI], X 1 is O or NH; X 2 is O or NH; R 4 is a saturated C 2-30 group.
  • R 4 has the structure: *-(CH2)4aX 4a (CH2)4b- # , wherein * represents the point of attachment to X 1 and # represents the point of attachment to X 2 ;
  • X 4a is null, CHR 4a , C(R 4a )2, O, NH, or NCH3;
  • R 4a is independently C1-8alkyl;
  • 4a is 0-12;
  • 4b is 0-12, wherein when X 4a is null, O, NH, or NCH3 the sum of 4a and 4b is at least 2, and when X 4a is CHR 4a or C(R 4a ) 2 the sum of 4a and 4b is at least 1.
  • the crosslinked polyurethane wherein X 1 is O or NH, X 2 is NH, X 4a is O, 4a is 2- 12, and 4b is 0.
  • the crosslinked polyurethane wherein 4a is 2-12, X 4a is null, and 4b is 0.
  • the crosslinked polyurethane wherein one of 4a and 4b is 1, and the other of 4a and 4b is 0, and X 4a is CHR 4a or C(R 4a )2.
  • X 4a is C(CH3)2.
  • [059] in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [CE] includes segments of Formula (5): X3 X4 R5 [Formula (5)], wherein the wavy lines represent t 3 4 o [DI], X is O or NH; X is O or NH; R 5 is an unsaturated C 2-30 group.
  • R 5 has the structure: *-(CH2)5aX 5a (CH2)5b- # , wherein * represents the point of attachment to X 3 and # represents the point of attachment to X 4 ;
  • the crosslinked polyurethane wherein one of 5a and 5b is 1, and the other of 5a and 5b is 0, and X 5a is CHR 5a or C(R 5a )2.
  • the crosslinked polyurethane wherein R 5a is C 2-4 alkenyl.
  • [CE] includes segments of Formula (6): [Formula (6)], wherein the wavy lines represent points of attachment to [DI], X 6 is O or NH; X 7 is O or NH; R 6 is a C 6-30 aromatic group.
  • the crosslinked polyurethane wherein [CC] is a segment of Formula (7): [Formula (7)], wherein the wavy lines represent to [DI], X 8 is O or NH; X 9 is O or NH; R 7 is an unsaturated C2-30 group.
  • the crosslinked polyurethane wherein X 8 and X 9 are both O, and R 7 is an unsaturated C 4-10 group having a single unsaturated carbon-carbon bond.
  • the crosslinked polyurethane wherein R 7 has the formula: , point of attachment to X 9 .
  • R cap is independently selected from OH, COOH, or NH 2 .
  • the crosslinked polyurethane is independently selected from a C1- 12 alkyl, C 6-12 aryl, or C 1-12 alkyl substituted one or more times by C 6-12 aryl.
  • the crosslinked polyurethane wherein (R cap ) is independently selected from a C 1- 12 haloalkyl, C6-12 haloaryl, C1-12 alkyl substituted one or more times by C6-12 haloaryl, or C1- 12 haloalkyl substituted one or more times by C 6-12 haloaryl.
  • R cap is independently selected from a C 1- 12 haloalkyl, C6-12 haloaryl, C1-12 alkyl substituted one or more times by C6-12 haloaryl, or C1- 12 haloalkyl substituted one or more times by C 6-12 haloaryl.
  • the crosslinked polyurethane wherein the crosslinking is conducted in the absence of a crosslinker.
  • the crosslinked polyurethane wherein the crosslinking is conducted in the presence of a crosslinker.
  • the crosslinked polyurethane of any preceding claim wherein the crosslinking is conducted in the presence of a crosslinker selected from a C 4-30 unsaturated group having at least two carbon-carbon double bonds, a C2-30 group having at least two azide groups, a C2-30 group having at least two amine or thiol groups.
  • crosslinked polyurethane wherein the crosslinking is conducted in the presence of a crosslinker comprising diallylmethyl amine, divinylbenze, ethylene glycol diacrylate, polyoxyethylene bis(azide), diethylene glycol bis(azidoacetate), 1,6 diazidohexane, 4,4′-bis(azidomethyl)-1,1′-biphenyl, ethylene glycol diacrylate, poly(ethylene glycol) diacrylate, neopentyl glycol diacrylate, trimethylolpropane triacrylate, pentaerythritol triacrylate, glycerol propoxylate triacrylate, trimethylolpropane propoxylate triacrylate, trimethylolpropane ethoxylate triacrylate, pentaerythritol tetraacrylate, di(trimethylolpropane) te
  • a crosslinker comprising diallylmethyl amine, divinylbenze, ethylene glyco
  • the crosslinked polyurethane wherein the crosslinker is present in an amount of 0.01-5 wt.%, 0.1-5 wt.%, 0.5-5 wt.%, 1-5 wt.%, 2.5-5 wt.%, 0.01-1 wt.%, or 0.5-2 wt.%.
  • aspects directed to a method of making the crosslinked polyurethane of any preceding claim comprising preparing a polyurethane by a process comprising the steps: preparing a first mixture comprising a macrodiol and disocyanate to give a first polyurethane, wherein the macrodiol comprises a poly(isobutylene) component; optionally forming a second reaction mixture comprising a chain extender and the first polyurethane to give a second polyurethane; and crosslinking the first polyurethane or second polyurethane.
  • the first reaction mixture comprises a chain extender.
  • the macrodiol can have an average molecular weight from 100-100,000 Da, from 100-50,000 Da, from 100-25,000 Da, from 100-10,000 Da, from 100- 5,000 Da, from 100-2,500 Da, from 100-1,000 Da, from 100-500 Da, from 250-1,000 Da, from 500-1,000 Da, from 500-1,500 Da, from 1,000-2,000 Da, from 1,000-3,000 Da, from 1,000-5,000 Da, from 1,500-2,500 Da, from 1,500-3,000 Da, from 2,500-5,000 Da, from 2,500-10,000 Da, from 5,000-10,000 Da, from 10,000-25,000 Da, from 10,000-50,000 Da, from 25,000-50,000 Da, from 25,000-75,000 Da, or from 50,000-100,000 Da.
  • the method wherein the macrodiol comprises a poly(alkenyl) component.
  • the macrodiol comprises poly(1,3-butadiene), poly(2,3- dimethyl-1,3-butadiene), or poly(isoprene), preferably poly(isoprene).
  • the method wherein the macrodiol comprises a poly(isoprene) component.
  • the method wherein the macrodiol comprises a poly(isobutylene-co-isoprene) random copolymer.
  • the method wherein the macrodiol comprises a poly(alkynyl) component.
  • the method wherein the macrodiol comprises a poly(alkyl) component, wherein the poly(alkyl) is not polyisobutylene.
  • the method wherein the macrodiol comprises a poly(ethylene) component.
  • the method wherein the macrodiol comprises a poly(isobutylene-co-isoprene) component.
  • the method wherein the macrodiol comprises a poly(isobutylene-co-ethylene) component.
  • the method wherein the macrodiol comprises a poly(isobutylene-co-ethylene-co- isoprene) component.
  • the macrodiol comprises a poly(meth)acrylate component.
  • the poly(meth)acrylate component comprises an oligomer derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec-butyl (meth)acrylate, isobutyl (meth)acrylate, 2- ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof.
  • the method wherein the macrodiol comprises a poly(siloxane) component.
  • the method wherein the macrodiol comprises a poly(dimethylsiloxane) component.
  • the macrodiol has the formula: HO-[-(A 1 ) d -(A 2 ) e -(A 3 ) f -(A 4 ) g -(A 5 ) h -(A 6 ) peg ]-OH, wherein A 1 is (isobutylene), and d is 1-10,000; A 2 is a C 1-20 alkenyl, and e is 0-500; A 3 is a C 1- 20alkynyl, and f is 0-500; A 4 is a C1-20alkyl, and g is 0-10,000; A 5 is a siloxane, and h is 0- 10,000; A 6 is a polyethylene glycol, and peg is 0-10,000, wherein d, e, f, g, h, and peg represent the number of monomer units.
  • a 2 has the formula: .
  • the macrodiol has the formula: HO-[isobutylenyl] i -[isoprenyl] m -[dimethylsiloxane] o -OH; HO-[isobutylenyl]i-[isoprenyl]m-[ethylenyl]n-[ dimethylsiloxane]o-OH; wherein: i is 1-10,000; n is 1-10,000; m is 1-50; and o is 0-10,000.
  • the method wherein the macrodiol comprises a polyisobutylene diol and a second diol that does not include a polyisobutylene component.
  • the second diol is a polyethylene diol, a siloxane diol, a polyethylene diol, or a combination thereof.
  • the diisocyanate comprises a compound of Formula (1a): [Formula (1a)], wherein R 1* is a saturated [0101]
  • R 1* has the formula: , [0102]
  • the diisocyanate comprises a compound of Formula (2a): [Formula (2a)], wherein R 2* is an [0103]
  • R 2* groups is: , .
  • the diisocyanate comprises a compound of Formula (3a): [Formula (3a)], wherein R 3* is a C6-30 [0105] T
  • R 3* has the formula: or aspects, disclosed is the method, wherein the chain extender comprises a compound of Formula (4a): [Formula (4a)], wherein X 1 is O or NH; X 2 is O 30 saturated aliphatic group.
  • R 4 has the structure: *-(CH2)4aX 4a (CH2)4b- # , wherein * represents the point of attachment to X 1 and # represents the point of attachment to X 2 ;
  • X 4a is null, CHR 4a , C(R 4a )2, O, NH, or NCH3;
  • R 4a is independently C1-8alkyl;
  • 4a is 0-12;
  • 4b is 0-12, wherein when X 4a is null, O, NH, or NCH 3 the sum of 4a and 4b is at least 2, and when X 4a is CHR 4a the sum of 4a and 4b is at least 1.
  • X 1 is O or NH
  • X 2 is NH
  • X 4a is O
  • 4a is 2-12
  • 4b is 0.
  • the method wherein 4a is 2-12
  • X 4a is null
  • 4b is 0.
  • the method wherein one of 4a and 4b is 1, and the other of 4a and 4b is 0, and X 4a is CHR 4a or C(R 4a )2.
  • X 4a is C(CH3)2.
  • the chain extender comprises a compound of Formula (5a): [Formula (5a)], X 3 is O or NH; X 4 is O or NH; aliphatic group.
  • R 5* has the structure: *-(CH2)5aX 5a (CH2)5b- # , wherein * represents the point of attachment to X 3 and # represents the point of attachment to X 4 ;
  • X 3 is O or NH
  • X 4 is NH
  • X 5a is O
  • 5b is 0.
  • 5a is 1-12
  • 5b is 1-12
  • one of 5a and 5b is 1, and the other of 5a and 5b is 0, and X 5a is CHR 5a or C(R 5a )2.
  • R 5a is C2-4alkenyl.
  • the chain extender comprises a compound of Formula (6a): [Formula (6a)], X 6 is O or NH; X 7 is O or NH; R 6* is a C2-30 aromatic group.
  • the chain connector comprises a compound of Formula (7a): [Formula (7a)], X 8 is O or NH; X 9 is O or NH; R 7* is an unsaturated C2-30 group. [0120] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein X 8 and X 9 are both O, and R 7* is an unsaturated C4-10 group having a single unsaturated carbon-carbon bond. [0121] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein R 7* has the formula: or point of attachment to X 9 .
  • the method wherein the polyurethane is not combined with a chain connector.
  • the method wherein the polyurethane is combined with a chain connector in an amount that is from 1-99% relative to polyurethane.
  • the medical device is an implantable heart valve.
  • the disclosed medical device comprises an annular frame comprising an inflow end and an outflow end and being radially compressible and expandable between a radially compressed configuration and a radially expanded configuration; a leaflet structure comprising one or more leaflets and positioned with the frame and secured thereto; and an inner skirt mounted inside of the frame, wherein at least one of the one or more leaflets or the inner skirt comprises any of the disclosed herein crosslinked polyurethanes.
  • the one or more leaflets comprise any of the disclosed herein crosslinked polyurethanes.
  • the inner skirt comprises any of the disclosed herein crosslinked polyurethanes.
  • the one or more leaflets exhibit a tensile strength of 20 MPa to 40 MPa.
  • the one or more leaflets exhibit an elastic modulus of 15 MPa to 25 MPa.
  • the one or more leaflets exhibit an elongation greater than 300%.
  • the inner skirt exhibits a tensile strength of 100 MPa to 200 MPa. [0133] In some aspects, in addition, or in alternative to any of the preceding aspects, the inner skirt exhibits an elastic modulus of 50 MPa to 150 MPa. [0134] In some aspects, in addition, or in alternative to any of the preceding aspects, the inner skirt exhibits an elongation of 100% to 150 %.
  • the disclosed medical device comprises one or more components of electrical simulations system, cardiac system, stents, grafts, scaffolds, catheters, vascular access ports, dialysis ports, dental implants, artificial ligaments, orthopedic prosthesis, or any combination there.
  • films comprising any of the disclosed herein crosslinked polyurethanes.
  • fibers comprising any of the disclosed herein crosslinked polyurethanes.
  • a yarn comprising any of the disclosed herein fibers.
  • a textile comprising any of the disclosed herein yarns.
  • the textile is woven or knitted.
  • a coating comprising any of the disclosed herein crosslinked polyurethanes.
  • a medical device comprising any of the disclosed herein films.
  • a medical device comprising any of the disclosed herein fibers.
  • a medical device comprising any of the disclosed herein textiles.
  • a medical device comprising any of the disclosed herein coatings.
  • FIGURE 1 is a perspective view of a prosthetic heart valve, according to one embodiment.
  • FIGURES 2-3 show an exemplary frame of the prosthetic heart valve of FIG.1.
  • FIGURES 4-5 show the assembly of an exemplary leaflet structure.
  • FIGURES 6-7 show the assembly of the leaflet structure with the inner skirt along a lower edge of the leaflets.
  • DETAILED DESCRIPTION [0146]
  • a reference to “a monomer” includes two or more monomers
  • a reference to “a device” includes two or more such devices and the like.
  • Ranges may be expressed herein as from “about” one particular value and/or to “about” another particular value. When such a range is expressed, another aspect includesfrom the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint and independently of the other endpoint.
  • the term “comprising” can also include the aspects “consisting of” and “consisting essentially of.” [0153]
  • the phrase “and without limitation” is understood to follow unless explicitly stated otherwise. It is further understood that these phrases are used for explanatory purposes only. “Exemplary” means “an example of” and is not intended to convey an indication of a preferred or ideal aspect. “Such as” is not used in a restrictive sense but for explanatory purposes.
  • a range of 1 to 50 is understood to include any number, combination of numbers, from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 or sub- ranges from the group consisting of 10-40, 20-50, 5-35, etc.
  • first may be used herein to describe various elements, components, regions, layers, and/or sections. These elements, components, regions, layers, and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer, or section from another element, component, region, layer, or section. Thus, a first element, component, region, layer, or section discussed below could be termed a second element, component, region, layer, or section without departing from the teachings of exemplary aspects.
  • spatially relative terms such as “beneath,” “below,” “lower,” “above,” “upper,” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the term “below” can encompass both an orientation of above and below.
  • the device may be otherwise oriented (rotated 90 degrees or at other orientations), and the spatially relative descriptors used herein are interpreted accordingly.
  • the term "substantially” means that the subsequently described event or circumstance completely occurs or that the subsequently described event or circumstance generally, typically, or approximately occurs.
  • the term “substantially” can in some aspects, refer to at least 80 %, at least 85 %, at least 90 %, at least 91 %, at least 92 %, at least 93 %, at least 94 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least 99 %, or 100 % of the stated property, component, composition, or other condition for which substantially is used to characterize or otherwise quantify an amount.
  • the term “substantially free,” when used in the context of a composition or component of a composition that is substantially absent, is intended to indicate that the recited component is not intentionally batched and added to the composition but can be present as an impurity along with other components being added to the composition.
  • the term “substantially free” is intended to refer to trace amounts that can be present in the batched components, for example, it can be present in an amount that is less than 1 % by weight, e.g., less than 0.5 % by weight, less than 0.1 % by weight, less than 0.05 % by weight, or less than 0.01 % by weight of the stated material, based on the total weight of the composition.
  • the term “substantially,” in, for example, the context “substantially identical” or “substantially similar,” refers to a method or a system, or a component that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% by similar to the method, system, or the component it is compared to.
  • the term or phrase “effective,” “effective amount,” or “conditions effective to” refers to such amount or condition that is capable of performing the function or property for which an effective amount or condition is expressed.
  • the attached figures may not show the various ways (readily discernable, based on this disclosure, by one of ordinary skill in the art) in which the disclosed system, method, and apparatus can be used in combination with other systems, methods, and apparatuses. Additionally, the description sometimes uses terms such as “produce” and “provide” to describe the disclosed method. These terms are high-level abstractions of the actual operations that can be performed. The actual operations that correspond to these terms can vary depending on the particular implementation and are, based on this disclosure, readily discernible by one of ordinary skill in the art. [0167] Disclosed are components that can be used to perform the disclosed methods and systems.
  • the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer.
  • Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions, Wiley Interscience, New York, 1981; Wilen et al., Tetrahedron 33:2725 (1977); Eliel, E.L.
  • Cxx group wherein xx is any number or range of numbers, refers to an organic fragment having the designated number of carbons. Unless specified to the contrary, the group may include one or more heteroatoms, so long as the specified number of carbon atoms is present.
  • the fragment may be a substituent or may represent a linking group connecting two or more other groups.
  • a group may be unsubstituted or substituted as defined herein.
  • a C 4 group includes (but is not limited to) the following fragments: . [0170] with the further requirement that the group include one or more non-aromatic carbon-carbon double bonds or carbon-carbon triple bonds.
  • a C 4-30 unsaturated group includes (but is not limited to) the following fragments: .
  • the term C xx group with the further requirement that the group does not include any non-aromatic carbon-carbon double bonds or carbon-carbon triple bonds.
  • a “saturated C xx group” may include one or more aromatic systems, so long as at least one sp 3 hybridized carbon atoms is present.
  • a C 4-30 saturated group includes (but is not limited to) the following fragments:
  • C1-6 alkyl is intended to encompass C1, C2, C3, C4, C5, C 6 , C 1-6 , C 1-5 , C 1-4 , C 1-3 , C 1-2 , C 2-6 , C 2-5 , C 2-4 , C 2-3 , C 3-6 , C 3-5 , C 3-4 , C 4-6 , C 4-5 , and C 5-6 alkyl.
  • alkyl refers to a radical of a straight-chain or branched hydrocarbon group having a specified range of carbon atoms (e.g., a "C1-16 alkyl” can have from 1 to 16 carbon atoms).
  • an alkyl group has 1 to 9 carbon atoms ("C1-9 alkyl").
  • An alkyl group can be saturated or unsaturated, i.e., an alkenyl or alkynyl group as defined herein. Unless specified to the contrary, an “alkyl” group includes both saturated alkyl groups and unsaturated alkyl groups.
  • An alkyl group may be monovalent or polyvalent, depending on the specific chemical context. By way of example, in the formula: , wherein R 1 and R 2 are each C 2- will be monovalent, while the R 2 alkyl will be divalent to accommodate bonding to both of the phenyl rings.
  • an alkyl group has 1 to 8 carbon atoms ("C1-8 alkyl”). In some aspects, an alkyl group has 1 to 7 carbon atoms ("C 1-7 alkyl”). In some aspects, an alkyl group has 1 to 6 carbon atoms ("C1-6 alkyl”). In some aspects, an alkyl group has 1 to 5 carbon atoms ("C 1-5 alkyl”). In some aspects, an alkyl group has 1 to 4 carbon atoms ("C 1-4 alkyl”). In some aspects, an alkyl group has 1 to 3 carbon atoms ("C1-3 alkyl”). In some aspects, an alkyl group has 1 to 2 carbon atoms ("C1-2 alkyl”).
  • an alkyl group has 1 carbon atom ("C1 alkyl”). In some aspects, an alkyl group has 2 to 6 carbon atoms (“C2-6 alkyl”).
  • Examples of C 1-6 alkyl groups include methyl (C 1 ), ethyl (C 2 ), propyl (C 3 ) (e.g., n- propyl, isopropyl), butyl (C 4 ) (e.g., n-butyl, tert-butyl, sec-butyl, iso-butyl), pentyl (C 5 ) (e.g., n-pentyl, 3-pentanyl, amyl, neopentyl, 3- methyl-2-butanyl, tertiary amyl), and hexyl (C6) (e.g., n-hexyl).
  • alkyl groups include n-heptyl (C 7 ), n-octyl (C 8 ), and the like. Unless otherwise specified, each instance of an alkyl group is independently unsubstituted (an "unsubstituted alkyl") or substituted (a "substituted alkyl") with one or more substituents (e.g., halogen, such as F).
  • substituents e.g., halogen, such as F
  • the alkyl group is an unsubstituted C 1-10 alkyl (such as unsubstituted C 1-6 alkyl, e.g., -CH 3 (Me), unsubstituted ethyl (Et), unsubstituted propyl (Pr, e.g., unsubstituted n-propyl (n-Pr), unsubstituted isopropyl (i-Pr)), unsubstituted butyl (Bu, e.g., unsubstituted n-butyl (n-Bu), unsubstituted tert-butyl (tert-Bu or t-Bu), unsubstituted sec-butyl (sec-Bu), unsubstituted isobutyl (i-Bu)).
  • C 1-10 alkyl such as unsubstituted C 1-6 alkyl, e.g., -CH 3 (Me), unsubstituted
  • the alkyl group is a substituted C1-10 alkyl (such as substituted C1-6 alkyl, e.g., -CF3, Bn).
  • haloalkyl is a substituted alkyl group, wherein one or more of the hydrogen atoms are independently replaced by a halogen, e.g., fluoro, bromo, chloro, or iodo.
  • the haloalkyl moiety has 1 to 8 carbon atoms ("C1-8 haloalkyl”).
  • the haloalkyl moiety has 1 to 6 carbon atoms ("C1-6 haloalkyl").
  • the haloalkyl moiety has 1 to 4 carbon atoms ("C1-4 haloalkyl”). In some aspects, the haloalkyl moiety has 1 to 3 carbon atoms ("C1-3 haloalkyl”). In some aspects, the haloalkyl moiety has 1 to 2 carbon atoms ("C 1-2 haloalkyl”). Examples of haloalkyl groups include -CHF 2 , -CH 2 F, -CF3, -CH2CF3, -CF2CF3, -CF2CF2CF3, -CCl3, -CFCl2, -CF2Cl, and the like.
  • hydroxyalkyl is a substituted alkyl group, wherein one or more of the hydrogen atoms are independently replaced by a hydroxyl.
  • the hydroxyalkyl moiety has 1 to 8 carbon atoms ("C1-8 hydroxyalkyl”).
  • the hydroxyalkyl moiety has 1 to 6 carbon atoms ("C 1-6 hydroxyalkyl”).
  • the hydroxyalkyl moiety has 1 to 4 carbon atoms ("C1-4 hydroxyalkyl”).
  • the hydroxyalkyl moiety has 1 to 3 carbon atoms ("C 1-3 hydroxyalkyl”).
  • the hydroxyalkyl moiety has 1 to 2 carbon atoms ("C1-2 hydroxyalkyl”).
  • alkoxy refers to an alkyl group, as defined herein, appended through an oxygen atom.
  • the alkoxy moiety has 1 to 8 carbon atoms ("C 1-8 alkoxy”).
  • the alkoxy moiety has 1 to 6 carbon atoms ("C1-6 alkoxy”).
  • the alkoxy moiety has 1 to 4 carbon atoms (“C 1-4 alkoxy”).
  • the alkoxy moiety has 1 to 3 carbon atoms ("C1-3 alkoxy").
  • the alkoxy moiety has 1 to 2 carbon atoms ("C 1-2 alkoxy”).
  • Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy and tert-butoxy.
  • haloalkoxy refers to a haloalkyl group, as defined herein, appended through an oxygen atom.
  • the alkoxy moiety has 1 to 8 carbon atoms ("C1-8 haloalkoxy”).
  • the alkoxy moiety has 1 to 6 carbon atoms ("C1-6 haloalkoxy").
  • the alkoxy moiety has 1 to 4 carbon atoms ("C1-4 haloalkoxy”). In some aspects, the alkoxy moiety has 1 to 3 carbon atoms ("C 1-3 haloalkoxy”). In some aspects, the alkoxy moiety has 1 to 2 carbon atoms ("C1-2 haloalkoxy”). Representative examples of haloalkoxy include, but are not limited to, difluoromethoxy, trifluoromethoxy, and 2,2,2-trifluoroethoxy. [0180] The term "alkoxyalkyl” is a substituted alkyl group, wherein one or more of the hydrogen atoms are independently replaced by an alkoxy group, as defined herein.
  • the alkoxyalkyl moiety has 1 to 8 carbon atoms ("C1-8 alkoxyalkyl”). In some aspects, the alkoxyalkyl moiety has 1 to 6 carbon atoms ("C 1-6 alkoxyalkyl”). In some aspects, the alkoxyalkyl moiety has 1 to 4 carbon atoms ("C1-4 alkoxyalkyl”). In some aspects, the alkoxyalkyl moiety has 1 to 3 carbon atoms ("C 1-3 alkoxyalkyl”). In some aspects, the alkoxyalkyl moiety has 1 to 2 carbon atoms ("C1-2 alkoxyalkyl”).
  • a C 3 alkoxyC 3 alkyl group includes, but is not limited to, the groups having the formula: –CH2CH2CH2OCH2CH2CH3, –CH2CH2CH2OCH(CH3)2, – CH(CH3)CH2OCH(CH3)2, [0181]
  • heteroalkyl refers to an alkyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (i.e., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain.
  • a heteroC 1-6 alkyl (which may also be designated a C1-6heteroalkyl) group includes, but is not limited to, the following structures: . group bonded through the specified heteroatom.
  • a OC 1-6 heteroalkyl group includes, but it not limited to, the following structures: . g from 1 to 20 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-20 alkyl").
  • a heteroalkyl group is a saturated group having 1 to 18 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC 1-18 alkyl").
  • a heteroalkyl group is a saturated group having 1 to 16 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC 1-16 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 14 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-14 alkyl”). In some aspects, a heteroalkyl group is a saturated group having 1 to 12 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC1-12 alkyl”). In some aspects, a heteroalkyl group is a saturated group having 1 to 10 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC1-10 alkyl").
  • a heteroalkyl group is a saturated group having 1 to 8 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-8 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 6 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-6 alkyl”). In some aspects, a heteroalkyl group is a saturated group having 1 to 4 carbon atoms and 1 or 2 heteroatoms within the parent chain (“heteroC1-4 alkyl”). In some aspects, a heteroalkyl group is a saturated group having 1 to 3 carbon atoms and 1 heteroatom within the parent chain (“heteroC1-3alkyl").
  • a heteroalkyl group is a saturated group having 1 to 2 carbon atoms and 1 heteroatom within the parent chain ("heteroC 1-2 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 carbon atom and 1 heteroatom (“heteroC 1 alkyl”). In some aspects, the heteroalkyl group defined herein is a partially unsaturated group having 1 or more heteroatoms within the parent chain and at least one unsaturated carbon, such as a carbonyl group. For example, a heteroalkyl group may comprise an amide or ester functionality in its parent chain such that one or more carbon atoms are unsaturated carbonyl groups.
  • each instance of a heteroalkyl group is independently unsubstituted (an "unsubstituted heteroalkyl") or substituted (a "substituted heteroalkyl") with one or more substituents.
  • the heteroalkyl group is an unsubstituted heteroC 1-20 alkyl.
  • the heteroalkyl group is an unsubstituted heteroC1-10alkyl.
  • the heteroalkyl group is a substituted heteroC 1-20 alkyl.
  • the heteroalkyl group is an unsubstituted heteroC 1-10 alkyl.
  • alkenyl refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 10 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, 3, or 4 double bonds).
  • an alkenyl group has 2 to 9 carbon atoms ("C2-9 alkenyl”).
  • an alkenyl group has 2 to 8 carbon atoms ("C2-8 alkenyl”).
  • an alkenyl group has 2 to 7 carbon atoms (“C 2-7 alkenyl”).
  • an alkenyl group has 2 to 6 carbon atoms (“C2-6alkenyl”).
  • an alkenyl group has 2 to 5 carbon atoms ("C 2-5 alkenyl”). In some aspects, an alkenyl group has 2 to 4 carbon atoms ("C2-4alkenyl”). In some aspects, an alkenyl group has 2 to 3 carbon atoms (“C2- 3 alkenyl”). In some aspects, an alkenyl group has 2 carbon atoms ("C 2 alkenyl”).
  • the one or more carbon-carbon double bonds can be internal (such as in 2- butenyl) or terminal (such as in 1-butenyl).
  • Examples of C 2-4 alkenyl groups include ethenyl (C 2 ), 1-propenyl (C 3 ), 2- propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), and the like.
  • Examples of C2-6 alkenyl groups include the aforementioned C 2-4 alkenyl groups as well as pentenyl (C 5 ), pentadienyl (C5), hexenyl (C6), and the like. Additional examples of alkenyl include heptenyl (C7), octenyl (C8), octatrienyl (C8), and the like.
  • each instance of an alkenyl group is independently unsubstituted (an "unsubstituted alkenyl") or substituted (a "substituted alkenyl") with one or more substituents.
  • the alkenyl group is an unsubstituted C 2-10 alkenyl.
  • the alkenyl group is a substituted C 2-10 alkenyl.
  • An alkenyl group may or polyvalent, which the skilled person will recognize is dependent on the specific chemical context.
  • heteroalkenyl refers to an alkenyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (i.e., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain.
  • heteroatom e.g., 1, 2, 3, or 4 heteroatoms
  • a heteroalkenyl group refers to a group having from 2 to 10 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain ("heteroC 2-10 alkenyl"). In some aspects, a heteroalkenyl group has 2 to 9 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain ("heteroC 2-9 alkenyl"). [0187] In some aspects, a heteroalkenyl group has 2 to 8 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC2-8alkenyl").
  • a heteroalkenyl group has 2 to 7 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain ("heteroC2-7alkenyl”). In some aspects, a heteroalkenyl group has 2 to 6 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC2-6alkenyl”). In some aspects, a heteroalkenyl group has 2 to 5 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain (“heteroC2-5alkenyl").
  • a heteroalkenyl group has 2 to 4 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain ("heteroC 2-4 alkenyl"). In some aspects, a heteroalkenyl group has 2 to 3 carbon atoms, at least one double bond, and 1 heteroatom within the parent chain (“heteroC2-3alkenyl”). In some aspects, a heteroalkenyl group has 2 to 6 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain (“heteroC2-6alkenyl").
  • each instance of a heteroalkenyl group is independently unsubstituted (an "unsubstituted heteroalkenyl") or substituted (a "substituted heteroalkenyl") with one or more substituents.
  • the heteroalkenyl group is an unsubstituted heteroC 2-10 alkenyl.
  • the heteroalkenyl group is a substituted heteroC2-10alkenyl.
  • alkynyl refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 10 carbon atoms and one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 triple bonds) (“C2-10alkynyl").
  • an alkynyl group has 2 to 9 carbon atoms ("C 2-9 alkynyl”). In some aspects, an alkynyl group has 2 to 8 carbon atoms ("C 2- 8alkynyl”). In some aspects, an alkynyl group has 2 to 7 carbon atoms (“C2-7alkynyl”). In some aspects, an alkynyl group has 2 to 6 carbon atoms ("C 2-6 alkynyl”). In some aspects, an alkynyl group has 2 to 5 carbon atoms (“C2-5alkynyl”). In some aspects, an alkynyl group has 2 to 4 carbon atoms ("C2-4alkynyl”).
  • an alkynyl group has 2 to 3 carbon atoms ("C2-3alkynyl”). In some aspects, an alkynyl group has 2 carbon atoms ("C2 alkynyl”).
  • the one or more carbon-carbon triple bonds can be internal (such as in 2-butynyl) or terminal (such as in 1-butynyl).
  • Examples of C 2-4 alkynyl groups include, without limitation, ethynyl (C 2 ), 1-propynyl (C 3 ), 2-propynyl (C 3 ), 1-butynyl (C 4 ), 2-butynyl (C 4 ), and the like.
  • C2-6 alkenyl groups include the aforementioned C2-4 alkynyl groups as well as pentynyl (C 5 ), hexynyl (C 6 ), and the like. Additional examples of alkynyl include heptynyl (C 7 ), octynyl (C8), and the like. Unless otherwise specified, each instance of an alkynyl group is independently unsubstituted (an "unsubstituted alkynyl") or substituted (a "substituted alkynyl”) with one or more substituents. In certain aspects, the alkynyl group is an unsubstituted C 2-10 alkynyl.
  • the alkynyl group is a substituted C 2-10 alkynyl.
  • An alkynyl group may be monovalent or polyvalent, as defined above for alkenyl.
  • heteroalkynyl refers to an alkynyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (i.e., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain.
  • a heteroalkynyl group refers to a group having from 2 to 10 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain ("heteroC 2-10 alkynyl"). In some aspects, a heteroalkynyl group has 2 to 9 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain ("heteroC2-9alkynyl"). In some aspects, a heteroalkynyl group has 2 to 8 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC2- 8alkynyl").
  • a heteroalkynyl group has 2 to 7 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain ("heteroC 2-7 alkynyl"). In some aspects, a heteroalkynyl group has 2 to 6 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain ("heteroC 2-6 alkynyl”). In some aspects, a heteroalkynyl group has 2 to 5 carbon atoms, at least one triple bond, and 1 or 2 heteroatoms within the parent chain (“heteroC 2-5 alkynyl").
  • a heteroalkynyl group has 2 to 4 carbon atoms, at least one triple bond, and l or 2 heteroatoms within the parent chain ("heteroC2- 4 alkynyl"). In some aspects, a heteroalkynyl group has 2 to 3 carbon atoms, at least one triple bond, and 1 heteroatom within the parent chain (“heteroC2-3alkynyl”). In some aspects, a heteroalkynyl group has 2 to 6 carbon atoms, at least one triple bond, and 1 or 2 heteroatoms within the parent chain (“heteroC2-6alkynyl").
  • each instance of a heteroalkynyl group is independently unsubstituted (an "unsubstituted heteroalkynyl") or substituted (a "substituted heteroalkynyl") with one or more substituents.
  • the heteroalkynyl group is an unsubstituted heteroC2-10alkynyl.
  • the heteroalkynyl group is a substituted heteroC 2-10 alkynyl.
  • carbocyclyl refers to a radical of a non- aromatic cyclic hydrocarbon group having from 3 to 14 ring carbon atoms ("C 3- 14carbocyclyl") and zero heteroatoms in the non-aromatic ring system.
  • a carbocyclyl group has 3 to 10 ring carbon atoms ("C 3-10 carbocyclyl”).
  • a carbocyclyl group has 3 to 8 ring carbon atoms (“C3-8carbocyclyl”).
  • a carbocyclyl group has 3 to 7 ring carbon atoms (“C 3-7 carbocyclyl”).
  • a carbocyclyl group has 3 to 6 ring carbon atoms ("C3-6carbocyclyl”). In some aspects, a carbocyclyl group has 4 to 6 ring carbon atoms ("C 4-6 carbocyclyl”). In some aspects, a carbocyclyl group has 5 to 6 ring carbon atoms ("C5-6carbocyclyl”). In some aspects, a carbocyclyl group has 5 to 10 ring carbon atoms (“C 5-10 carbocyclyl”).
  • Exemplary C 3-6 carbocyclyl groups include, without limitation, cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), and the like.
  • Exemplary C3-8carbocyclyl groups include, without limitation, the aforementioned C 3-6 carbocyclyl groups as well as cycloheptyl (C 7 ), cycloheptenyl (C 7 ), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptanyl (C7), bicyclo[2.2.2]octanyl (C8), and the like.
  • Exemplary C3-10 carbocyclyl groups include, without limitation, the aforementioned C3-8 carbocyclyl groups as well as cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C10), cyclodecenyl (C10), octahydro-1H-indenyl (C9), decahydronaphthalenyl (C 10 ), spiro[4.5]decanyl (C 10 ), and the like.
  • the carbocyclyl group is either monocyclic (“monocyclic carbocyclyl”) or polycyclic (e.g., containing a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic carbocyclyl”) or tricyclic system (“tricyclic carbocyclyl”)) and can be saturated or can contain one or more carbon-carbon double or triple bonds.
  • Carbocyclyl also includes ring systems wherein the carbocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups wherein the point of attachment is on the carbocyclyl ring, and in such instances, the number of carbons continues to designate the number of carbons in the carbocyclic ring system.
  • each instance of a carbocyclyl group is independently unsubstituted (an "unsubstituted carbocyclyl") or substituted (a "substituted carbocyclyl”) with one or more substituents.
  • the carbocyclyl group is an unsubstituted C 3-14 carbocyclyl.
  • the carbocyclyl group is a substitute C3-14 carbocyclyl.
  • “carbocyclyl” is a monocyclic, saturated carbocyclyl group having from 3 to 14 ring carbon atoms ("C 3-14 cycloalkyl”).
  • a cycloalkyl group has 3 to 10 ring carbon atoms ("C3-10cycloalkyl”).
  • a cycloalkyl group has 3 to 8 ring carbon atoms (“C 3-8 cycloalkyl”).
  • a cycloalkyl group has 3 to 6 ring carbon atoms ("C3-6cycloalkyl”).
  • a cycloalkyl group has 4 to 6 ring carbon atoms ("C 4-6 cycloalkyl”). In some aspects, a cycloalkyl group has 5 to 6 ring carbon atoms ("C5-6cycloalkyl”). In some aspects, a cycloalkyl group has 5 to 10 ring carbon atoms ("C5- 10 cycloalkyl”). Examples of C 5-6 cycloalkyl groups include cyclopentyl (C 5 ) and cyclohexyl (C6).
  • C3-6 cycloalkyl groups include the aforementioned C5-6 cycloalkyl groups as well as cyclopropyl (C 3 ) and cyclobutyl (C 4 ).
  • C 3-8 cycloalkyl groups include the aforementioned C3-6 cycloalkyl groups, as well as cycloheptyl (C7) and cyclooctyl (C8).
  • each instance of a cycloalkyl group is independently unsubstituted (an "unsubstituted cycloalkyl") or substituted (a "substituted cycloalkyl") with one or more substituents.
  • the cycloalkyl group is an unsubstituted C3-14 cycloalkyl. In certain aspects, the cycloalkyl group is a substituted C3-14 cycloalkyl.
  • heterocyclyl refers to an aromatic (also referred to as a heteroaryl), unsaturated, or saturated cyclic hydrocarbon that includes at least one heteroatom in the cycle.
  • heterocyclyl refers to a radical of a 3- to 14-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("3-14 membered heterocyclyl").
  • the point of attachment can be a carbon or nitrogen atom, as valency permits.
  • a heterocyclyl group can either be monocyclic (“monocyclic heterocyclyl”) or polycyclic (e.g., a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic heterocyclyl”) or tricyclic system (“tricyclic heterocyclyl”)), and can be saturated or can contain one or more carbon-carbon double or triple bonds.
  • Heterocyclyl polycyclic ring systems can include one or more heteroatoms in one or both rings.
  • Heterocyclyl also includes ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more carbocyclyl groups wherein the point of attachment is either on the carbocyclyl or heterocyclyl ring, or ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclyl ring, and in such instances, the number of ring members continues to designate the number of ring members in the heterocyclyl ring system.
  • each instance of heterocyclyl is independently unsubstituted (an "unsubstituted heterocyclyl") or substituted (a "substituted heterocyclyl") with one or more substituents.
  • the heterocyclyl group is an unsubstituted 3-14 membered heterocyclyl.
  • the heterocyclyl group is a substituted 3-14 membered heterocyclyl.
  • a heterocyclyl group is a 5-10 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-10 membered heterocyclyl").
  • a heterocyclyl group is a 5-8 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-8 membered heterocyclyl").
  • a heterocyclyl group is a 5-6 membered non-aromatic ring system having ring carbon atoms and 1- 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-6 membered heterocyclyl").
  • the 5-6 membered heterocyclyl has 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur.
  • the 5-6 membered heterocyclyl has 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some aspects, the 5-6 membered heterocyclyl has a 1 ring heteroatom selected from nitrogen, oxygen, and sulfur.
  • Exemplary 3-membered heterocyclyl groups containing 1 heteroatom include, without limitation, aziridinyl, oxiranyl, and thiiranyl.
  • Exemplary 4-membered heterocyclyl groups containing 1 heteroatom include, without limitation, azetidinyl, oxetanyl, and thietanyl.
  • Exemplary 5-membered heterocyclyl groups containing 1 heteroatom include, without limitation, tetrahydrofuranyl, dihydrofurany1, tetrahydrothiopheny1, dihydrothiopheny1, pyrrolidiny1, dihydropyrrolyl, and pyrrolyl-2,5-dione.
  • Exemplary 5- membered heterocyclyl groups containing 2 heteroatoms include, without limitation, dioxolanyl, oxathiolanyl and dithiolanyl.
  • Exemplary 5-membered heterocyclyl groups containing 3 heteroatoms include, without limitation, triazolinyl, oxadiazolinyl, and thiadiazolinyl.
  • Exemplary 6-membered heterocyclyl groups containing 1 heteroatom include, without limitation, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl.
  • Exemplary 6-membered heterocyclyl groups containing 2 heteroatoms include, without limitation, piperazinyl, morpholinyl, dithianyl, and dioxanyl.
  • Exemplary 6-membered heterocyclyl groups containing 3 heteroatoms include, without limitation, triazinyl.
  • Exemplary 7- membered heterocyclyl groups containing 1 heteroatom include, without limitation, azepanyl, oxepanyl and thiepanyl.
  • Exemplary 8-membered heterocyclyl groups containing 1 heteroatom include, without limitation, azocanyl, oxecanyl and thiocanyl.
  • Exemplary bicyclic heterocyclyl groups include, without limitation, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, tetrahydrobenzothienyl, tetrahydrobenzofuranyl, tetrahydroindolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydrochromenyl, octahydroisochromenyl, decahydronaphthyridinyl, decahydro-1,8- naphthyridinyl, octahydropyrrolo[3,2-b]pyrrole,
  • aryl refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 ⁇ electrons shared in a cyclic array) having 6-14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system ("C6-14aryl”).
  • an aryl group has 6 ring carbon atoms ("C6aryl”; e.g., phenyl).
  • an aryl group has 10 ring carbon atoms ("C10aryl”; e.g., naphthyl such as 1-naphthyl and 2-naphthyl).
  • an aryl group has 14 ring carbon atoms ("C14aryl”; e.g., anthracyl).
  • Aryl also includes ring systems wherein the aryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the radical or point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system.
  • each instance of an aryl group is independently unsubstituted (an "unsubstituted aryl") or substituted (a "substituted aryl”) with one or more substituents.
  • the aryl group is an unsubstituted C6-14aryl. In certain aspects, the aryl group is a substituted C 6-14 aryl.
  • heteroaryl refers to a radical of a 5-14 membered monocyclic or polycyclic (e.g., bicyclic, tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 ⁇ electrons shared in a cyclic array) having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-14 membered heteroaryl").
  • heteroaryl groups that contain one or more nitrogen atoms
  • the point of attachment can be a carbon or nitrogen atom, as valency permits.
  • Heteroaryl polycyclic ring systems can include one or more heteroatoms in one or both rings.
  • Heteroaryl includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heteroaryl ring system.
  • Heteroaryl also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused polycyclic (aryl/heteroaryl) ring system.
  • a heteroaryl group is a 5-10 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-10 membered heteroaryl").
  • a heteroaryl group is a 5-8 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-8 membered heteroaryl").
  • a heteroaryl group is a 5-6 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-6 membered heteroaryl”).
  • the 5-6 membered heteroaryl has 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur.
  • the 5-6 membered heteroaryl has 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some aspects, the 5-6 membered heteroaryl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Unless otherwise specified, each instance of a heteroaryl group is independently unsubstituted (an "unsubstituted heteroaryl") or substituted (a "substituted heteroaryl") with one or more substituents. In certain aspects, the heteroaryl group is an unsubstituted 5-14 membered heteroaryl. In certain aspects, the heteroaryl group is a substituted 5-14 membered heteroaryl.
  • Exemplary 5-membered heteroaryl groups containing 1 heteroatom include, without limitation, pyrrolyl, furanyl, and thiophenyl.
  • Exemplary 5-membered heteroaryl groups containing 2 heteroatoms include, without limitation, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl.
  • Exemplary 5-membered heteroaryl groups containing 3 heteroatoms include, without limitation, triazolyl, oxadiazolyl, and thiadiazolyl.
  • Exemplary 5-membered heteroaryl groups containing 4 heteroatoms include, without limitation, tetrazolyl.
  • Exemplary 6- membered heteroaryl groups containing 1 heteroatom include, without limitation, pyridinyl.
  • Exemplary 6-membered heteroaryl groups containing 2 heteroatoms include, without limitation, pyridazinyl, pyrimidinyl, and pyrazinyl.
  • Exemplary 6-membered heteroaryl groups containing 3 or 4 heteroatoms include, without limitation, triazinyl and tetrazinyl, respectively.
  • Exemplary 7- membered heteroaryl groups containing 1 heteroatom include, without limitation, azepinyl, oxepinyl, and thiepinyl.
  • Exemplary 5,6- bicyclic heteroaryl groups include, without limitation, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl.
  • Exemplary 6,6- bicyclic heteroaryl groups include, without limitation, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl.
  • Exemplary tricyclic heteroaryl groups include, without limitation, phenanthridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenothiazinyl, phenoxazinyl, and phenazinyl.
  • alk refers to an alkyl group (as defined herein) connecting the named substitutent with the rest of the compound.
  • alkaryl which is a subset of alkyl refers to an alkyl group substituted by an aryl group, wherein the point of attachment is on the alkyl moiety
  • alkheteroaryl (which is a subset of "alkyl") refers to an alkyl group substituted by a heteroaryl group, wherein the point of attachment is on the alkyl moiety.
  • the number of carbons atoms may be specified in the alkyl chain, the named substituent, or both.
  • C 1-2 alkC 6 aryl refers to a phenyl ring (which may be substituted) connected via a 1-2 carbon alkylene group.
  • Affixing the suffix "-ene" to a group indicates the group is a polyvalent moiety, e.g., boned to two or more groups.
  • Alkylene is the polyvalent moiety of alkyl
  • alkenylene is the divalent moiety of alkenyl
  • alkynylene is the divalent moiety of alkynyl
  • heteroalkylene is the divalent moiety of heteroalkyl
  • heteroalkenylene is the divalent moiety of heteroalkenyl
  • heteroalkynylene is the divalent moiety of heteroalkynyl
  • carbocyclylene is the divalent moiety of carbocyclyl
  • heterocyclylene is the divalent moiety of heterocyclyl
  • arylene is the divalent moiety of aryl
  • heteroarylene is the divalent moiety of heteroaryl.
  • alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted.
  • Optionally substituted refers to a group which may be substituted or unsubstituted (e.g., “substituted” or “unsubstituted” alkyl, “substituted” or “unsubstituted” alkenyl, “substituted” or “unsubstituted” alkynyl, “substituted” or “unsubstituted” heteroalkyl, “substituted” or “unsubstituted” heteroalkenyl, "substituted” or “unsubstituted” heteroalkynyl, "substituted” or “unsubstituted” carbocyclyl, "substituted” or “unsubstituted” heterocyclyl, "substituted” or “unsubstituted” aryl or “substituted” or “unsubstituted” heteroaryl group).
  • substituted means that at least one hydrogen present on a group is replaced with a permissible substituent, e.g., a substituent which, upon substitution, results in a stable compound, e.g., a compound that does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction.
  • a "substituted” group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position.
  • substituted is contemplated to include substitution with all permissible substituents of organic compounds and includes any of the substituents described herein that results in the formation of a stable compound.
  • the present disclosure contemplates any and all such combinations in order to arrive at a stable compound.
  • heteroatoms such as nitrogen may have hydrogen substituents and/or any suitable substituent as described herein, which satisfy the valencies of the heteroatoms and result in the formation of a stable moiety.
  • the disclosure is not intended to be limited in any manner by the exemplary substituents described herein.
  • halo or halogen refers to fluorine (fluoro, -F), chlorine (chloro, -Cl), bromine (bromo, -Br), or iodine (iodo, -I).
  • hydroxyl or “hydroxy” refers to the group -OH.
  • substituted amino refers to a monosubstituted amino, a disubstituted amino, or a trisubstituted amino.
  • substituted amino is a monosubstituted amino or a disubstituted ammino group.
  • trisubstituted amino refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with three groups, and includes groups selected from -N(R bb )2 and -N(R bb )3 + X – , wherein R bb and X – are as defined herein.
  • sulfonyl refers to a group selected from -SO2N(R bb )2, -SO2R aa , and SO2OR aa , wherein R aa and R bb are as defined herein.
  • acyl groups include aldehydes (-CHO), carboxylic acids (-CO2H), ketones, acyl halides, esters, amides, imines, carbonates, carbamates, and ureas.
  • Acyl substituents include but are not limited to, any of the substituents described herein that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alky
  • a polyvalent moiety without specifying the specific order of attachment is intended to cover all possible arrangements.
  • a chemical bond depicted: represents either a single, double, or triple bond, valency permitting.
  • d An ele pulls electron density towards itself, away from other portions of the molecule, e.g., through resonance and/or inductive effects.
  • Exemplary electron-withdrawing groups include F, Cl, Br, I, NO2, CN, SO2R, SO3R, SO2NR2, C(O)R 1a ; C(O)OR, and C(O)NR2 (wherein R is H or an alkyl, aryl, heteroaryl, cycloalkyl, heterocyclyl group) as well as alkyl group substituted with one or more of those group [0223]
  • An electron-donating group is a functional group or atom that pushes electron density away from itself, towards other portions of the molecule, e.g., through resonance and/or inductive effects.
  • Exemplary electron-donating groups include unsubstituted alkyl or aryl groups, OR and N(R) 2 and alkyl groups substituted with one or more OR and N(R) 2 groups.
  • a formula with chemical bonds shown only as solid lines and not as wedges or dashed lines contemplates each possible isomer, e.g., each enantiomer, diastereomer, and meso compound, and a mixture of isomers, such as a racemic or scalemic mixture.
  • a formula depicting one or more stereochemical features does not exclude the presence of other isomers.
  • Some compounds disclosed herein may exist as one or more tautomers.
  • Tautomers are interconvertible structural isomers that differ in the position of one or more protons or other labile atom.
  • the prevalence of one tautomeric form over another will depend on the specific chemical compound as well as its local chemical environment.
  • the depiction of one tautomeric form is inclusive of all possible tautomeric forms.
  • a substituent drawn without explicitly specifying the point of attachment indicates that the substituent may be attached at any possible atom.
  • the substituent may be present at any one of the six possible carbon atoms.
  • the term “(meth)acrylic acid” refers to a genus of compounds, including both acrylic acid and methacrylic acid. The same convention is used with reference to (meth)acrylates, (meth)acrylamides, and polymers containing the same.
  • Compounds disclosed herein may be provided in the form of salts.
  • the compounds may be provided in the form of biocompatible salts.
  • biocompatible salts are those which can be combined with biofluids and tissues (for example, blood) without significantly adversely affecting any of the components of said biofluids and tissues.
  • Biocompatible salts also include those which do not include any toxic or otherwise harmful ionic species.
  • the skilled person understands that when biofluids, like blood, come into contact with salts there can be an ionic exchange, leading to the introduction of ionic species into a subject. Accordingly, for implementations in which the composite membranes are used in a clinical setting, the composite membranes will not include any species that can exchange to the point of being toxic or harmful to the patient.
  • the compounds may be provided as acid addition salts formed with inorganic acids, for example, hydrochloric, hydrobromic, sulfuric, phosphoric, and nitric acids and the like; salts formed with organic acids such as acetic, oxalic, tartaric, succinic, maleic, fumaric, gluconic, citric, malic, methanesulfonic, p-toluenesulfonic, napthalenesulfonic, and polygalacturonic acids, and the like; salts formed from elemental anions such as chloride, bromide, and iodide; salts formed from metal hydroxides, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, and magnesium hydroxide; salts formed from metal carbonates, for example, sodium carbonate, potassium carbonate, calcium carbonate, and magnesium carbonate; salts formed from metal bicarbonates, for example, sodium bicarbonate and potassium bicarbonate; salts
  • an ionizable group may exist in neutral or ionic form, or both.
  • the depiction of one ionic form is inclusive of all other forms.
  • the designation of a polymeric or oligomeric system having the formula: — [Unit A] x —[Unit B] y — indicates that the polymer or oligomer is composed of the depicted units in the ratio specified by the x and y subscript, but in the absence of an indication to the contrary, it does not imply any particular order or arrangement of the units.
  • the formula: — [Unit A] 2 —[Unit B] 3 — includes, but is not limited to: [Unit B]—[Unit A]—[Unit B]—[Unit A]—[Unit B]; [Unit B]—[Unit B]—[Unit B]—[Unit A]—[Unit A]; and [Unit B]—[Unit B]—[Unit A]—[Unit A]—[Unit B].
  • the subscript units typically refer to the relative ratio of the individual monomer units used to prepare the polymeric or oligomeric system, assuming 100% conversion of the monomer unit that is the limiting reagent.
  • the relative ratio can be expressed as a weight ratio, mole ratio, or volume ratio.
  • POLYMERS It is known in the polymer chemistry that a polyurethane molecular structure comprised of polyols (usually macrodiols) forming the soft segment, where the hard segment is composed of diisocyanates, chain extenders (microdiols) and the urethane linkages. When used in vivo for medical device applications, the degradation of the polyurethanes is primarily caused by the bond breakage in the polyol groups, the soft segments of the macromolecule.
  • the disclosure is directed to the compositional combinations involving poly(isobutylene) (PIB) based polyurethanes that would overcome the susceptibility of the soft segments by chemistry modification that will further improve the biostability of PIB polyurethanes.
  • PIB poly(isobutylene)
  • biostable crosslinked polyurethanes prepared by crosslinking a polyurethane having the formula: wherein a is from 1-10,000; b is from 1-10,000; c is from 0-500; R cap is a capping group; [soft] represents a macrodiol segment including a poly(isobutylene) component; [DI] represents a diisocyante component; [CE] represents a chain extender component; [CC] represents a chain connector component, wherein one or more of [soft], [DI], [CE], and [CC] include one or more crosslinkable groups.
  • the biostable crosslinked polyurethanes disclosed herein are prepared from polyurethanes that can have a molecular weight from 50,000 g/mol to 1,000,000 g/mol, including exemplary values of 75,000 g/mol, 100,000 g/mol, 150,000 g/mol, 200,000 g/mol, 300,000 g/mol, 400,000 g/mol, 500,000 g/mol, 600,000 g/mol, 700,000 g/mol, 800,000 g/mol, 900,000 g/mol, and 950,000 g/mol.
  • the molecular weight of the polyurethane that is used to prepare the biostable crosslinked polyurethanes is from 100,000 g/mol to 300,000 g/mol, including exemplary values of 110,000 g/mol, 120,000 g/mol, 130,000 g/mol, 140,000 g/mol, 150,000 g/mol, 160,000 g/mol, 170,000 g/mol, 180,000 g/mol, 190,000 g/mol, 200,000 g/mol, 210,000 g/mol, 220,000 g/mol, 230,000 g/mol, 240,000 g/mol, 250,000 g/mol, 260,000 g/mol, 270,000 g/mol, 280,000 g/mol, 290,000 g/mol, and 295,000 g/mol.
  • a crosslinkable group is a functional group capable of undergoing a reaction to form a covalent bond.
  • crosslinkable groups include carbon-carbon double bonds, carbon-carbon triple bonds, epoxides, carboxylic acids and activated carboxylic acids, Michael acceptors (i.e., ⁇ , ⁇ unsaturated carbonyls and sulfones), a clickable group (i.e., a functional group capable of undergoing a click ligation reaction, e.g., 2,3 dipolar cycloaddition, an inverse electron demand Diels-Alder cycloaddition, a thiol-ene reaction).
  • Michael acceptors i.e., ⁇ , ⁇ unsaturated carbonyls and sulfones
  • a clickable group i.e., a functional group capable of undergoing a click ligation reaction, e.g., 2,3 dipolar cycloaddition, an inverse electron demand Diels-Alder cycloaddition, a thiol-ene reaction.
  • crosslinkable groups can directly crosslink with another of the same functional group, i.e., carbon-carbon double bonds and carbon-carbon triple bonds, while other functional groups must be paired in order to form a covalent bond (suitable pairs include alkyne:azide, epoxide:amine, epoxide:alcohol, epoxide:carboxylic acid, sulfide:olefin; Michael acceptor:amine, Michael acceptor:sulfide, etc.
  • the second functional group is also part of the polyurethane or may be provided as part of a separate crosslinking agent.
  • a polyurethane having terminal-alkyne functional groups may be crosslinked by copper catalyzed click reaction with a bis-azido compound.
  • an olefin-containing polyurethane may be crosslinked in the absence of an additional crosslinker, while in other implementations, an olefin-containing polyurethane may be crosslinked in the presence of a crosslinker, for example, a divinyl compound (2,2-bis[4-(2-hydroxy-3-methacryloxy-propoxy)phenyl]propane, tetraethylene glycol diacrylate, 1,9-nonanediol dimethacrylate, divinylbenzene).
  • a crosslinker for example, a divinyl compound (2,2-bis[4-(2-hydroxy-3-methacryloxy-propoxy)phenyl]propane, tetraethylene glycol diacrylate, 1,9-nonanediol dimethacrylate, divinylbenzene).
  • polyurethane crosslinked by an additional crosslinking agent does not exclude the possibility that some portion of the polyurethane may be self-crosslinked, depending upon the chemistry.
  • the crosslinking agent may be provided in a given weight ratio relative to the polyurethane.
  • the crosslinking agent is present in an amount that is 0.01-50 wt.%, including exemplary values of 0.05 wt %, 0.1 wt %, 0.5 wt %, 0.7 wt %, 1.0 wt %, 2.5 wt %, 3 wt %, 3.5 wt %, 4 wt %, 4.5 wt %, 5 wt %, 5.5 wt %, 6 wt %, 6.5 wt %, 7 wt %, 7.5 wt %, 8 wt %, 8.5 wt %, 9 wt %, 9.5 wt %, 10 wt %, 12.5 wt %, 15 wt %, 17.5 wt %, 20 wt %, 25 wt %, 30 wt %, 35 wt %, 40 wt %, 45 wt %,
  • the given wt.% percent refers to the total mass of the combined crosslinking agents.
  • the crosslinking agent is present in an amount that is 0.01-10 wt.%, 0.01-5 wt.%, 0.01-2.5 wt.%, 0.01-1 wt.%, 0.01-0.5 wt.%, 0.1-5 wt.%, 0.1-2.5 wt.%, 0.1-1 wt.%, 0.1-0.5 wt.%, 0.5-5 wt.%, 0.5-2.5 wt.%, 0.5-1 wt.%, 1-5 wt.%, 1-2.5 wt.%, 2.5-5 wt.%, 3.5-10 wt.%, 5-10 wt.%, 5-15 wt.%, 10-20 wt.%, or 15-25 wt.%, relative to the total mass of the polyurethane.
  • the crosslinking agent is present in an amount that is from 0.01 wt % to 10 wt %, including exemplary values of 0.01 wt.%, 0.05 wt.%, 0.1 wt.%, 0.25 wt.%, 0.5 wt.%, 0.75 wt.%, 1 wt.%, 2 wt.%, 2.5 wt.%, 3 wt.%, 4 wt.%, 5 wt.%, 7.5 wt.%, and 9.5 wt.%, relative to the total mass of the polyurethane.
  • the [soft] and [CE] components may be present in a variety of different ratios.
  • the [soft] component is present in an amount from 1-99 wt.%, including exemplary values of 2.5 wt %, 5 wt %, 7.5 wt %, 10 wt %, 15 wt %, 20 wt %, 25 wt %, 30 wt %, 35 wt %, 40 wt %, 45 wt %, 50 wt %, 55 wt %, 60 wt %, 65 wt %, 70 wt %, 75 wt %, 80 wt %, 85 wt %, 90 wt %, and 95 wt % relative to the [CE] component.
  • the wt% refers to the relative weight of macrodiol and chain extender compounds used to prepare the polyurethane.
  • the [soft] unit is present in an amount from 1-25 wt.%, including exemplary values of 1 wt %, 2 wt %, 3 wt %, 4 wt %, 5 wt %, 6 wt %, 7 wt %, 8 wt %, 9 wt %, 10 wt %, 11 wt %, 12 wt %, 13 wt %, 14 wt %, 15 wt %, 16 wt %, 17 wt %, 18 wt %, 19 wt %, 20 wt %, 21 wt %, 22 wt %, 23 wt %, and 24 wt %; from 25-50 wt.%, including
  • the [soft] unit is present in an amount of 90-99.9 wt.%, including exemplary values of 91 wt%, 91.5 wt%, 92 wt%, 92.5 wt%, 93 wt%, 93.5 wt%, 94 wt%, 94.5 wt%, 95 wt%, 95.5 wt%, 96 wt%, 96.5 wt%, 97 wt%, 97.5 wt%, 98 wt%, 98.5 wt%, 99 wt%, and 99.5 wt% relative to the [CE] portion.
  • the [soft] unit is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97- 99 wt.%, or from 99-99.99 wt.%, relative to the [CE] component. [0242] In some implementations, the [soft] unit is present in an amount of 90% by weight relative to the [CE] component.
  • the [soft] unit is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the [CE] component.
  • the [soft] unit is present in an amount of at least 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2.5 wt.%, 1 wt.%, or at least 0.5 wt.%, relative to the [CE] component.
  • the [soft] unit is present in an amount of 0.5 wt.% to 80 wt.%, including exemplary values of 1 wt%, 2.5 wt%, 5 wt%, 10 wt%, 20 wt%, 30 wt%, 40 wt%, 50 wt%, 60 wt%, and 70 wt%.
  • the polyurethane may be self-crosslinked (i.e., a functional group in one polyurethane forms a covalent bond with a functional group in a second polyurethane), or the polyurethane may be crosslinked in the presence of the crosslinking agent, i.e., a compound having two or more functional groups, wherein one functional group forms a covalent bond with one polyurethane, and another functional group on the same molecule forms a covalent bond with a second polyurethane.
  • Soft component [0245]
  • the [soft] component can be provided as a macrodiol having a given average molecular weight.
  • the macrodiol has a molecular weight from 100-100,000 Da, from 100-50,000 Da, from 100-25,000 Da, from 100-10,000 Da, from 100- 5,000 Da, from 100-2,500 Da, from 100-1,000 Da, from 100-500 Da, from 250-1,000 Da, from 500-1,000 Da, from 500-1,500 Da, from 1,000-2,000 Da, from 1,000-3,000 Da, from 1,000-5,000 Da, from 1,500-2,500 Da, from 1,500-3,000 Da, from 2,500-5,000 Da, from 2,500-10,000 Da, from 5,000-10,000 Da, from 10,000-25,000 Da, from 10,000-50,000 Da, from 25,000-50,000 Da, from 25,000-75,000 Da, or from 50,000-100,000 Da.
  • the macrodiol can have a molecular weight that has any value between any two mentioned above ranges.
  • the [soft] unit includes a poly(alkenyl) component.
  • the poly(alkenyl) is a poly(1,3-butadiene), poly(2,3-dimethyl-1,3- butadiene), or poly(isoprene), preferably poly(isoprene), e.g., a poly(isobutylene-co- isoprene).
  • the poly(isobutylene-co-isoprene) component is a random copolymer.
  • the poly(isobutylene-co-isoprene) component is a block copolymer.
  • the [soft] unit includes a poly(isobutylene-co-isoprene) component, wherein the isobutylene portion is present in an amount of 0.1-99 wt.%, including exemplary values of 0.5 wt %, 5 wt %, 7.5 wt %, 10 wt %, 15 wt %, 20 wt %, 25 wt %, 30 wt %, 35 wt %, 40 wt %, 45 wt %, 50 wt %, 55 wt %, 60 wt %, 65 wt %, 70 wt %, 75 wt %, 80 wt %, 85 wt %, 90 wt %, and 95 wt % relative to the isoprene portion
  • the isobutylene portion is present in any values between any foregoing values or within a range formed by any of the foregoing values.
  • the isobutylene portion is present in an amount 0.5 wt % to 95 wt %, or 1 wt% to 90 wt%, or 5 wt % to 85 wt %, or 1 wt % to 85 wt % or 10 wt % to 70 wt %, or 1 wt % to 70 wt%, or 1 wt % to 60 wt % or 1 wt % to 50 wt %, and so one.
  • the isobutylene portion is present in an amount from 1-25 wt.%, including exemplary values of 1 wt %, 2 wt %, 3 wt %, 4 wt %, 5 wt %, 6 wt %, 7 wt %, 8 wt %, 9 wt %, 10 wt %, 11 wt %, 12 wt %, 13 wt %, 14 wt %, 15 wt %, 16 wt %, 17 wt %, 18 wt %, 19 wt %, 20 wt %, 21 wt %, 22 wt %, 23 wt %, and 24 wt %; from 25-50 wt.%, including exemplary values of 26 wt %, 27 wt %, 28 wt %, 29 wt %, 30 wt %, 31 wt %,
  • the [soft] unit includes a poly(isobutylene-co-isoprene) component, wherein the isobutylene portion is present in an amount of 90-99.9 wt.%, including exemplary values of 91 wt%, 91.5 wt%, 92 wt%, 92.5 wt%, 93 wt%, 93.5 wt%, 94 wt%, 94.5 wt%, 95 wt%, 95.5 wt%, 96 wt%, 96.5 wt%, 97 wt%, 97.5 wt%, 98 wt%, 98.5 wt%, 99 wt%, and 99.5 wt% relative to the isoprene portion.
  • the isobutylene portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the isoprene. [0249] In some implementations, the isobutylene portion is present in an amount of 90% by weight relative to the isoprene portion.
  • the isobutylene portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the isoprene.
  • the isobutylene portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2.5 wt.%, 1 wt.%, or 0.5 wt.%, relative to the isoprene portion.
  • the isobutylene portion is present in an amount of 0.5 wt.% to 80 wt.%, including exemplary values of 1 wt%, 2.5 wt%, 5 wt%, 10 wt%, 20 wt%, 30 wt%, 40 wt%, 50 wt%, 60 wt%, and 70 wt% relative to the isoprene portion.
  • the [soft] unit includes a poly(alkylene) component.
  • the poly(alkylene) is a polyethylene, polypropylene, poly(ethylene- co-propylene) polymer.
  • the poly(alkylene) is block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In certain implementations, the poly(alkylene) is a random copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In such aspects, it is hypothesized that the presence of poly(alkylene) can affect the crystallinity of the polymer, for example, making the polymer more crystalline and, as a result, more fatigue-resistant. In still further aspects, it is assumed that the presence of poly(alkylene) components can minimize the phase separation of the hard segments of the polymer.
  • the poly(alkylene) portion is present in an amount of 1-99 wt.%, including exemplary values of 2.5 wt %, 5 wt %, 7.5 wt %, 10 wt %, 15 wt %, 20 wt %, 25 wt %, 30 wt %, 35 wt %, 40 wt %, 45 wt %, 50 wt %, 55 wt %, 60 wt %, 65 wt %, 70 wt %, 75 wt %, 80 wt %, 85 wt %, 90 wt %, and 95 wt % relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(alkylene) portion is present in an amount from 1- 25 wt% including exemplary values of 1 wt %, 2 wt %, 3 wt %, 4 wt %, 5 wt %, 6 wt %, 7 wt %, 8 wt %, 9 wt %, 10 wt %, 11 wt %, 12 wt %, 13 wt %, 14 wt %, 15 wt %, 16 wt %, 17 wt %, 18 wt %, 19 wt %, 20 wt %, 21 wt %, 22 wt %, 23 wt %, and 24 wt %; from 25-50 wt.%, including exemplary values of 26 wt %, 27 wt %, 28 wt %, 29 wt %, 30 wt %, 31 wt
  • the poly(alkylene) portion is present in an amount from 90- 95 wt.%, including exemplary values of 90.5 wt.%, 91 wt.%, 91.5 wt.%, 92 wt.%, 92.5 wt.%, 93 wt.%, 93.5 wt.%, 94 wt.%, and 94.5 wt.%; from 95-99 wt.%, including exemplary values of 95.5 wt.%, 96 wt.%, 96.5 wt.%, 97 wt.%, 97.5 wt.%, 98 wt.%, 98.5 wt.%,; from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(alkylene) portion is present in an amount from 1- 10 wt.%, including exemplary values of 2 wt.%, 3 wt.%, 4 wt.%, 5 wt.%, 6 wt.%, 7 wt.%, 8 wt.%, and 9 wt.%; from 5-15 wt.%, including exemplary values of 6 wt.%, 7 wt.%, 8 wt.%, 9 wt.%, 10 wt.%, 11 wt.%, 12 wt.%, 13 wt.%, and 1 wt.%; from 10-25 wt.%, including exemplary values of 11 wt.%, 12 wt.%, 13 wt.%, 14 wt.%, 15 wt.%, 16 wt.%, 17 wt.%, 18 wt.%, 19 wt.%, 20 wt.%, 21
  • the poly(alkylene) portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0257] In some implementations, the poly(alkylene) portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(alkylene) portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the poly(alkylene) portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the [soft] unit includes a poly(meth)acrylate portion.
  • the poly(meth)acrylate is derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec- butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof.
  • the poly(meth)acrylate is a block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component. In certain implementations, the poly(meth)acrylate is a random copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component. [0260] In some implementations, the poly(meth)acrylate portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(meth)acrylate portion is present in an amount from 1-25 wt.%, from 25-50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood, and as disclosed above, the poly(meth)acrylate portion can be present in any amount that falls between any of the two mentioned above ranges.
  • the poly(meth)acrylate portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood, and as disclosed above, the poly(meth)acrylate portion can be present in any amount that falls between any of the two mentioned above ranges.
  • the poly(meth)acrylate portion is present in an amount from 1-10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood, and as disclosed above, the poly(meth)acrylate portion can be present in any amount that falls between any of the two mentioned above ranges. [0263] In some implementations, the poly(meth)acrylate portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(meth)acrylate portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co- isoprene) portion. It is also understood that the poly(meth)acrylate portion can be present in any amount in any range between any of the disclosed amounts.
  • the poly(meth)acrylate portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the poly(meth)acrylate portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%,10 wt.%, 5 wt.%, 2 wt.%,1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(meth)acrylate portion can be present in any amount in any range between any of the disclosed amounts.
  • the [soft] unit includes a poly(siloxane) component in addition to the polyisobutylene segment.
  • the poly(siloxane) is a poly(dimethylsiloxane), a poly(vinyl-methylsiloxane), or a poly(divinylsiloxane.
  • the poly(siloxane) is a block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component.
  • polysiloxane components can increase the softness, flexibility and elasticity of the polymer.
  • the poly(siloxane) portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(siloxane) portion is present in an amount from 1-25 wt.%, from 25- 50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(siloxane) portion can be present in an amount that falls between any two values disclosed above.
  • the poly(siloxane) portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be present in an amount that falls between any two values disclosed above.
  • the poly(siloxane) portion is present in an amount from 1- 10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be present in an amount that falls between any two values disclosed above. [0270] In some implementations, the poly(siloxane) portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(siloxane) portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is also understood that the poly(siloxane) portion can be present in an amount in any range between any of the disclosed amounts.
  • the poly(siloxane) portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the poly(siloxane) portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%,10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(siloxane) portion can be present in an amount in any range between any of the disclosed amounts.
  • the [soft] unit includes a polyethylene glycol component in addition to the polyisobutylene segment.
  • the polyethylene glycol has a molecular weight (in Daltons) from 100-100,000, from 500-10,000, from 1,000-50,000, from 500-2,500, from 2,500-7,500, from 5,000-10,000, from 10,000-25,000, from 25,000- 50,000, or from 50,000-100,000. It is further understood that the polyethylene glycol can have a molecular weight value that falls between any two mentioned above values.
  • the polyethylene glycol portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the polyethylene glycol portion is present in an amount from 1-25 wt.%, from 25-50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be present in an amount that falls between any two values disclosed above.
  • the polyethylene glycol portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be present in an amount that falls between any two values disclosed above.
  • the polyethylene glycol portion is present in an amount from 1-10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be present in an amount that falls between any two values disclosed above. [0277] In some implementations, the polyethylene glycol portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the polyethylene glycol portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co- isoprene) portion. It is also understood that the polyethylene glycol portion can be present in an amount in any range between any of the disclosed amounts.
  • the polyethylene glycol portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the polyethylene glycol portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%,10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the polyethylene glycol portion can be present in an amount in any range between any of the disclosed amounts.
  • the [soft] segment can have the formula: -[-(A 1 )d-(A 2 )e-(A 3 )f-(A 4 )g-(A 5 )h-(A 6 )peg]-, wherein A 1 is (isobutylene), and d is 1-10,000; A 2 is C4-20alkenyl, and e is 0-500; A 3 is C 4-20 alkynyl, and f is 0-500; A 4 is C 2-20 alkyl, and g is 0-10,000; A 5 is a siloxane, and h is 0-10,000; A 6 is a polyethylene glycol, and peg is 0-10,000 wherein d, e, f, g, h, and peg represent the number of monomer units.
  • d is from 1-10,000, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 200, 500, 1,000, 5,000, and 9,000. It is understood that these values are only exemplary, and any values of d in the disclosed range or any range between any disclosed values can be used.
  • e is from 0 to 500, including exemplary values 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 200, 300, and 400. It is understood that these values are only exemplary, and any values of e in the disclosed range or any range between any disclosed values can be used.
  • f is from 0 to 500, including exemplary values 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 200, 300, and 400.
  • g is from 1-10,000, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 50,100, 200, 500, 1,000, 5,000, and 9,000. It is understood that these values are only exemplary, and any value of g in the disclosed range or any range between any disclosed values can be used.
  • h is from 1-10,000, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 200, 500, 1,000, 5,000, and 9,000. It is understood that these values are only exemplary, and any values of h in the disclosed range or any range between any disclosed values can be used.
  • peg is from 1-10,000, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 200, 500, 1,000, 5,000, and 9,000. It is understood that these values are only exemplary and any value of peg in the disclosed range or any range between any disclosed values can be used.
  • d’ is present in an amount of 1-100 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, and 99.5 wt.%. It is understood that these values are only exemplary and any values of d’ in the disclosed range or any range between any disclosed values can be used.
  • e’ is present in an amount of 1-99 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, 98.5, and 98.5 wt.%. It is understood that these values are only exemplary and any values of e’ in the disclosed range or any range between any disclosed values can be used.
  • f’ is present in an amount of 1-99 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, 98.5, and 98.5 wt.%. It is understood that these values are only exemplary and any values of f’ in the disclosed range or any range between any disclosed values can be used.
  • g’ is present in an amount of 1-99 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, 98.5, and 98.5 wt.%. It is understood that these values are only exemplary and any values of g’ in the disclosed range or any range between any disclosed values can be used.
  • h’ is present in an amount of 1-99 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, 98.5, and 98.5 wt.%. It is understood that these values are only exemplary and any values of h’ in the disclosed range or any range between any disclosed values can be used.
  • peg’ is present in an amount of 1-99 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, 98.5, and 98.5 wt.%. It is understood that these values are only exemplary and any values of peg’ in the disclosed range or any range between any disclosed values can be used.
  • a 4 is a mixture of (ethylene) and (propylene), while in other aspects, A 4 is (ethylene).
  • a 2 is (1,3-butadiene), (2,3-dimethyl-1,3-butadiene), (isoprene), or a combination thereof. In some implementations, A 2 is (isoprene). [0286] In some implementations, A 5 is (dimethylsiloxane). [0287] In some implementations, A 3 and A 6 are absent, i.e., f, f’, peg, and peg’ are all 0.
  • [DI] can include a segment of Formula (1): [Formula (1)], wherein the wavy lines to any of [soft], [CE], or [CC], wherein R 1 is a saturated C2-30 group.
  • Exemplary R 1 groups include: , , or [Formula (2)], wherein the wavy lines to any of [soft], [CE], or [CC], wherein R 2 is an unsaturated C 2-30 group.
  • Exemplary R 2 groups include: , . [0290] In [Formula (3)], wherein the wavy lines to any of [soft], [CE], or [CC], wherein R 3 is a C 6-30 aromatic group.
  • the C 6-30 aromatic group refers to a divalent fragment in which each carbon atom in the shortest sequence of atoms from one nitrogen to the next is part of an aromatic system. Such systems may include sp 3 hybridized carbons, so long as such carbons are not part of the shortest path from one nitrogen to the next.
  • Exemplary R 3 groups include: . Ch [0291]
  • [CE] includes segments of Formula (4): [Formula (4)], wherein the wavy lines to [DI], X 1 is O or NH; X 2 is O or NH; R 4 is a saturated C2-30 group.
  • R 4 has the structure: *-(CH2)4aX 4a (CH2)4b- # , wherein * represents the point of attachment to X 1 and # represents the point of attachment to X 2 ;
  • X 4a is null, CHR 4a , C(R 4a )2,O, NH, or NCH3;
  • R 4a is independently C1-8alkyl;
  • 4a is 0-12;
  • 4b is 0-12, wherein when X 4a is null, O, NH, or NCH3 the sum of 4a and 4b is at least 2, and when X 4a is CHR 4a or C(R 4a ) 2 , the sum of 4a and 4b is at least 1.
  • X 1 is O or NH
  • X 2 is NH
  • X 4a is O
  • 4a is 2-12
  • 4b is 0.
  • one of 4a and 4b is 1, and the other of 4a and 4b is 0, and X 4a is CHR 4a or C(R 4a ) 2 .
  • X 4a is C(CH3) 2 .
  • [CE] includes segments of Formula (5): [Formula (5)], wherein the wavy lines to [DI], X 3 is O or NH; X 4 is O or NH; R 5 is an unsaturated C2-30 group.
  • R 5 has the structure: *-(CH 2 ) 5a X 5a (CH 2 ) 5b - # , wherein * represents the point of attachment to X 3 and # represents the point of attachment to X 4 ;
  • one of 5a and 5b is 1, and the other of 5a and 5b is 0, and X 5a is CHR 5a or C(R 5a ) 2 .
  • R 5a is C 2-4 alkenyl, for example, allyl or vinyl.
  • [DI] only includes segments of Formula (4) and does not include any segments of Formula (5).
  • [DI] only includes segments of Formula (5) and does not include any segments of Formula (4).
  • [DI] can include a mixture of Formula (4) and Formula (5).
  • [DI] can include the segment of Formula (4) in an amount from 1-99% relative to the segment of Formula (5).
  • the ratio refers to the mole ratio of the diisocyanate monomers used to prepare the polyurethane.
  • [DI] can include the segment of Formula (4) in an amount from 1-25%, from 10-25%, from 25-50%, from 50-75%, from 75-99%, or from 90-99%, relative to the segment of Formula (5).
  • [DI] can include the segment of Formula (4) in an amount that is 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 85% relative to the segment of Formula (5). [0304] In some implementations, [DI] can include the segment of Formula (4) in an amount from 90-99.99%, from 90-95%, from 95-99%, from 95-97%, from 97-99%, or from 98-99%, relative to the segment of Formula (5). In some implementations, [DI] can include the segment of Formula (4) in an amount that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% relative to the segment of Formula (5).
  • the C6-30 aromatic group refers to a divalent fragment in which each carbon atom in the shortest sequence of atoms from X 6 to X 7 is part of an aromatic system. Such systems may include sp 3 hybridized carbons, so long as such carbons are not part of the shortest path from X 6 to X 7 .
  • Chain connector [0307]
  • [CC] is a segment of Formula (7): [Formula (7)], wherein the wavy lines to [DI], X 8 is O or NH; X 9 is O or NH; R 7 is an unsaturated C2-30 group.
  • X 8 and X 9 are both O, and R 7 is an unsaturated C4-10 group having a single unsaturated carbon-carbon bond. Exemplary R 7 groups include: or point of attachment to X 9 .
  • the polyurethane does not include any [CC].
  • [CC] may be present in an amount that is from 1-99% relative to [DI].
  • the ratio refers to the mole ratio of the diisocyanate monomers and chain extender monomers used to prepare the polyurethane. When more than one diisocyanate monomer is used, the ratio refers to the sum total of all moles of all diisocyanate compounds.
  • [DI] can be present in an amount that is from 1-25%, from 10-25%, from 25-50%, from 50-75%, from 75-99%, or from 90-99%, relative to [CC]. In some implementations, [DI] can be present in an amount that is 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 85% relative to [CC]. [0311] In some implementations, [DI] can be present in an amount from 90-99.99%, from 90-95%, from 95-99%, from 95-97%, from 97-99%, or from 98-99%, relative to [CC].
  • [DI] can be present in an amount that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% relative to [CC].
  • Capping group R cap
  • the capping group (R cap ) may simply be an unreacted end of component fragments, e.g., OH, COOH, or NH2 (an unreacted isocyanate is hydrolyzed to a primary amine in the presence of water).
  • a capping reagent may be added to terminate the polyurethane polymerization process and install a capping group on the polyurethane.
  • the capping group can be a C 1-12 alkyl, C 6-12 aryl, or C 1- 12 alkyl substituted one or more times by C6-12 aryl.
  • the capping group can be resistant to a chemical reaction. Without wishing to be bound by theory, the resistance to chemical reactions can improve oxidative stability, resistance to hydrolysis, and resistance to enzymatic degradation.
  • the capping group is a C1-12 haloalkyl, C 6-12 haloaryl, or C 1-12 haloalkyl substituted one or more times by C 6-12 haloaryl. Fluorine is a preferred halogen substituent.
  • the capping group can be a perfluoroalkyl group or perfluoroaryl, for example, CF 3 , CF 2 CF 3 , C 6 F 5 , and the like, while in some instances, the capping group can be a partially fluorinated alkyl group or partially fluorinated aryl group, for example, CH 2 CF 3 , C 6 F 3 H 2 , and the like.
  • the crosslinked polyurethanes described herein may be prepared by the steps: preparing a first mixture comprising a macrodiol (as defined herein) and disocyanate to give a first polyurethane, optionally capping the first polyurethane to give a first capped polyurethane, optionally forming a second reaction mixture comprising a chain extender and the first polyurethane to give a second polyurethane, optionally capping the second polyurethane to give a second capped polyurethane; and crosslinking the first polyurethane, first capped polyurethane, second polyurethane or second capped polyurethane.
  • the crosslinking may be conducted in the presence of an additional crosslinking agent, and in other implementations, the crosslinking may be conducted in the absence of any separate crosslinking agent.
  • the polyurethane may be subjected to two or more crosslinking reactions. For example, the polyurethane may first be crosslinked in the absence of a separate crosslinking agent, and then subsequently crosslinked in the presence of an additional crosslinking agent.
  • the polyurethane may first be crosslinked in the presence of a separate crosslinking agent, and then subsequently crosslinked in the absence of an additional crosslinking agent.
  • the polyurethane may first be crosslinked in the presence of a first additional crosslinking agent, and then subsequently crosslinked in the presence of a second additional crosslinking agent.
  • the polyurethane may first be crosslinked in the absence of a separate crosslinking agent using a first set of crosslinking conditions, and then subsequently crosslinked in the absence of a separate crosslinking agent, using a second set of crosslinking conditions, wherein the second set of conditions is different from the first.
  • Crosslinking may be performed by exposing the crosslinkable polyurethane to radiation such as electron beam or ultraviolet (UV) radiation, or heat.
  • the crosslinkable composition may be exposed to heated air or gas, wherein the heated air or gas has a temperature from 25 to 200 °C., from 50-200 °C., from 100 to 200 °C., from 150-200 °C from 25 to 100 °C., from 50-100 °C, or from 100 to 150 °C. It is understood that any values between any two foregoing values can be included. [0319] The heating can be conducted for a period from 0.1–120 minutes, from 1–120 minutes, from 5–120 minutes, from 10–120 minutes, from 30–120 minutes, from 60–120 minutes, from 0.1–60 minutes, from 30–60 minutes, from 1–30 minutes, from 1–10 minutes, from 10–30, or from 20-30 minutes.
  • any values between any two foregoing values can be included.
  • an accelerating voltage of 75-350 kV can be used, and a dosage of 5 to 250 kilogray (kGy) can be utilized.
  • kGy kilogray
  • UV a light source of 200 nm to 450 nm is suitable.
  • the power rating of the lamp needed depends on the composition and can be any emitting irradiation at a dosage of at least 0.001 mJ/cm 2 .
  • the dosage is from 0.01 to 2000 mJ/cm 2 , from 0.1 to 1000 mJ/cm 2 , from 1 to 1000 mJ/cm 2 , or from 10 to 500 mJ/cm 2 . It is understood that any values between any two foregoing values can be included.
  • the crosslinking agent can be a C 4-30 unsaturated group having at least two carbon-carbon double bonds. In some implementations, the crosslinking agent is a C 6-18 unsaturated group, or a C 6-12 unsaturated group. Such crosslinking agents may be used when the polyurethane includes one or more carbon-carbon double bonds or carbon- carbon triple bonds.
  • Exemplary agents include diallylmethyl amine, divinylbenze, and ethylene glycol diacrylate.
  • the crosslinking agent can be a C2-30 group having at least two azide groups.
  • the crosslinking agent is a C2-12 group having at least two azide groups.
  • Such crosslinking agents may be used when the polyurethane includes one or more terminal alkynes.
  • Exemplary agents include polyoxyethylene bis(azide), diethylene glycol bis(azidoacetate), 1,6 diazidohexane, and 4, 4’-bis(azidomethyl)-1,1’- biphenyl.
  • the crosslinking agent can be a C2-30 group having at least two amine or thiol groups. In some implementations, the crosslinking agent is a C2-12 group having at least two amine or thiol groups.
  • Such crosslinking agents may be used when the polyurethane includes one or more epoxides or Michael acceptors (e.g., ⁇ , ⁇ unsaturated carbonyl or sulfone).
  • the crosslinking agent can be ethylene glycol diacrylate, poly(ethylene glycol) diacrylate, neopentyl glycol diacrylate, trimethylolpropane triacrylate, pentaerythritol triacrylate, glycerol propoxylate triacrylate, trimethylolpropane propoxylate triacrylate, trimethylolpropane ethoxylate triacrylate, pentaerythritol tetraacrylate, di(trimethylolpropane) tetraacrylate, divinylbenzene, divinyl sulfone, 1,4-butanediol divinyl ether, ethylene glycol divinyl ether, di- tri-, and poly-ethylene glycol divinyl ether.
  • the macrodiol can have an average molecular weight from 100-100,000 Da, from 100-50,000 Da, from 100-25,000 Da, from 100-10,000 Da, from 100-5,000 Da, from 100- 2,500 Da, from 100-1,000 Da, from 100-500 Da, from 250-1,000 Da, from 500-1,000 Da, from 500-1,500 Da, from 1,000-2,000 Da, from 1,000-3,000 Da, from 1,000-5,000 Da, from 1,500-2,500 Da, from 1,500-3,000 Da, from 2,500-5,000 Da, from 2,500-10,000 Da, from 5,000-10,000 Da, from 10,000-25,000 Da, from 10,000-50,000 Da, from 25,000-50,000 Da, from 25,000-75,000 Da, or from 50,000-100,000 Da.
  • the macrodiol can have a molecular weight value that falls between any two disclosed above values.
  • the macrodiol includes a poly(alkenyl) component.
  • the poly(alkenyl) is a poly(1,3-butadiene), poly(2,3-dimethyl-1,3- butadine), or poly(isoprene), preferably poly(isoprene), e.g., a poly(isobutylene-co-isoprene).
  • the poly(isobutylene-co-isoprene) component is a random copolymer.
  • the poly(isobutylene-co-isoprene) component is a block copolymer.
  • the macrodiol includes a poly(isobutylene-co-isoprene) component, wherein the isobutylene portion is present in an amount of 1-99 wt.% relative to the isoprene portion. In some implementations, the isobutylene portion is present in an amount from 1-25 wt.%, from 25-50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25- 75 wt.%, relative to the isoprene.
  • the poly(isobutylene-co-isoprene) component can be present in any value that falls within the disclosed ranges.
  • the macrodiol includes a poly(isobutylene-co-isoprene) component, wherein the isobutylene portion is present in an amount of 90-99.9 wt.% relative to the isoprene portion.
  • the isobutylene portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99- 99.99 wt.%, relative to the isoprene.
  • the poly(isobutylene-co-isoprene) component can be present in any value that falls within the disclosed ranges.
  • the isobutylene portion is present in an amount of 90% by weight relative to the isoprene portion.
  • the isobutylene portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the isoprene. It is understood that the isobutylene portion can be in any range that can be formed by the disclosed above values relative to the isoprene.
  • the isobutylene portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2.5 wt.%, 1 wt.%, or 0.5 wt.%, relative to the isoprene portion. It is understood that the isobutylene portion can be in any range that can be formed by the disclosed above values relative to the isoprene.
  • the macrodiol includes a poly(alkylene) component.
  • the poly(alkylene) is a polyethylene, polypropylene, poly(ethylene- co-propylene) polymer. In certain implementations, the poly(alkylene) is block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In certain implementations, the poly(alkylene) is a random copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0332] In some implementations, the poly(alkylene) portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(alkylene) portion is present in an amount from 1-25 wt.%, from 25- 50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(alkylene) portion can be present in any value that falls within the disclosed ranges.
  • the poly(alkylene) portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(alkylene) portion can be present in any value that falls within the disclosed ranges.
  • the poly(alkylene) portion is present in an amount from 1- 10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(alkylene) portion can be present in any value that falls within the disclosed ranges. [0335] In some implementations, the poly(alkylene) portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(alkylene) portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(alkylene) portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene- co-isoprene) portion. [0337] In some implementations, the poly(alkylene) portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(alkylene) portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2 wt.%,1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(alkylene) portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the macrodiol includes a poly(meth)acrylate portion.
  • the poly(meth)acrylate is derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec- butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof.
  • the poly(meth)acrylate is a block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component. In certain implementations, the poly(meth)acrylate is a random copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component. [0339] In some implementations, the poly(meth)acrylate portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(meth)acrylate portion is present in an amount from 1-25 wt.%, from 25-50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(meth)acrylate portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(meth)acrylate portion can be present in any value that falls within the disclosed ranges.
  • the poly(meth)acrylate portion is present in an amount from 1-10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(meth)acrylate portion can be present in any value that falls within the disclosed ranges. [0342] In some implementations, the poly(meth)acrylate portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(meth)acrylate portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co- isoprene) portion.
  • the poly(meth)acrylate portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0344] In some implementations, the poly(meth)acrylate portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(meth)acrylate portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%,10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(meth)acrylate portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the macrodiol includes a poly(siloxane) component in addition to the polyisobutylene segment.
  • the poly(siloxane) is a poly(dimethylsiloxane), a poly(vinyl-methylsiloxane), or a poly(divinylsiloxane.
  • the poly(siloxane) is a block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component.
  • the poly(siloxane) portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(siloxane) portion is present in an amount from 1-25 wt.%, from 25- 50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be present in any value that falls within the disclosed ranges.
  • the poly(siloxane) portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be present in any value that falls within the disclosed ranges.
  • the poly(siloxane) portion is present in an amount from 1- 10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be present in any value that falls within the disclosed ranges. [0349] In some implementations, the poly(siloxane) portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(siloxane) portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(siloxane) portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene- co-isoprene) portion. [0351] In some implementations, the poly(siloxane) portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(siloxane) portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the poly(siloxane) portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the macrodiol includes a polyethylene glycol component in addition to the polyisobutylene segment.
  • the polyethylene glycol has a molecular weight (in Daltons) from 100-100,000, from 500-10,000, from 1,000- 50,000, from 500-2,500, from 2,500-7,500, from 5,000-10,000, from 10,000-25,000, from 25,000-50,000, or from 50,000-100,000.
  • the polyethylene glycol can have any molecular weight that falls within any two disclosed above values.
  • the polyethylene glycol portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the polyethylene glycol portion is present in an amount from 1-25 wt.%, from 25-50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the polyethylene glycol portion can be present in any value that falls within the disclosed ranges.
  • the polyethylene glycol portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be present in any value that falls within the disclosed ranges.
  • the polyethylene glycol portion is present in an amount from 1-10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be present in any value that falls within the disclosed ranges. [0356] In some implementations, the polyethylene glycol portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the polyethylene glycol portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co- isoprene) portion.
  • the polyethylene glycol portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0358] In some implementations, the polyethylene glycol portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the polyethylene glycol portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • the macrodiol segment can have the formula: HO-[-(A 1 )d-(A 2 )e-(A 3 )f-(A 4 )g-(A 5 )h-(A 6 )peg]-OH, wherein A 1 is (isobutylene), and d is 1-10,000; A 2 is C 4-20 alkenyl, and e is 0-500; A 3 is C 4-20 alkynyl, and f is 0-500; A 4 is C 2-20 alkyl, and g is 0-10,000; A 5 is a siloxane, and h is 0-10,000; A 6 is a polyethylene glycol, and peg is 0-10,000 wherein d, e, f, g, h, and peg represent the number of monomer units.
  • a 4 is a mixture of (ethylene) and (propylene), while in other aspects, A 4 is (ethylene).
  • a 2 is (1,3-butadiene), (2,3-dimethyl-1,3-butadine), (isoprene), or a combination thereof. In some implementations, A 2 is (isoprene).
  • a 5 is (dimethylsiloxane).
  • a 3 and A 6 are absent, i.e., f, f’, peg, and peg’ are all 0.
  • the macrodiol can be combined with a diisocyanate that includes a compound of Formula (1a): [Formula (1a)], wherein R 1* is a R 1* groups include: , , or t includes a compound of Formula (2a): [Formula (2a)], wherein R 2* is an R 2* groups include: , . [0367]
  • a compound of Formula (3a): [Formula (3a)] wherein R 3* is a C 6-30 the context R 3* , the C6-30 aromatic group refers to a divalent fragment in which each carbon atom in the shortest sequence of atoms from one nitrogen to the next is part of an aromatic system.
  • Such systems may include sp 3 hybridized carbons, so long as such carbons are not part of the shortest path from one nitrogen to the next.
  • exemplary R 3 groups include: .
  • Chain extender compound [0368]
  • the macrodiol and diisocyanate can be combined with a chain extender compound of Formula (4a): [Formula (4a)], X 1 is O or NH; X 2 is O or NH; R 4* is a saturated C 2-30 group.
  • R 4* has the structure: *-(CH2)4aX 4a (CH2)4b- # , wherein * represents the point of attachment to X 1 and # represents the point of attachment to X 2 ;
  • X 4a is null, CHR 4a , C(R 4a ) 2 ,O, NH, or NCH 3 ;
  • R 4a is independently C 1-8 alkyl; 4a is 0-12; and 4b is 0-12, wherein when X 4a is null, O, NH, or NCH3, the sum of 4a and 4b is at least 2, and when X 4a is CHR 4a , the sum of 4a and 4b is at least 1.
  • X 1 is O or NH
  • X 2 is NH
  • X 4a is O
  • 4a is 2-12
  • 4b is 0.
  • one of 4a and 4b is 1, and the other of 4a and 4b is 0, and X 4a is CHR 4a .
  • X 4a is C(CH3)2.
  • the macrodiol and diisocyanate can be combined with a chain extender compound of Formula (5a): [Formula (5a)], X 3 is O or NH; X 4 is O or NH; R 5* is an unsaturated C 2-30 group.
  • R 5* has the structure: *-(CH 2 ) 5a X 5a (CH 2 ) 5b - # , wherein * represents the point of attachment to X 3 and # represents the point of attachment to X 4 ;
  • the diisocyanate can include a mixture of Formula (4a) and Formula (5a).
  • the diisocyanate can include a compound of Formula (4a) in an amount from 1-99% relative to the compound of Formula (5a).
  • the ratio refers to the mole ratio of the compounds of Formula (4a) and (5a) [0380]
  • the diisocyanate can include the compound of Formula (4a) in an amount from 1-25%, from 10-25%, from 25-50%, from 50-75%, from 75-99%, or from 90-99%, relative to the compound of Formula (5a).
  • the diisocyanate can include the compound of Formula (4a) in an amount that is 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 85% relative to the compound of Formula (5a). [0381] In some implementations, the diisocyanate can include the compound of Formula (4a) in an amount from 90-99.99%, from 90-95%, from 95-99%, from 95-97%, from 97- 99%, or from 98-99%, relative to the compound of Formula (5a). In some implementations, the diisocyanate can include the compound of Formula (4a) in an amount that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% relative to the compound of Formula (5a).
  • the macrodiol when the diisocyanate includes the compound of Formula (5a), the macrodiol will not include a poly(alkenyl) component. In other implementations, when the diisocyanate does not include a compound of Formula (5a), the macrodiol does include a poly(alkenyl) component, e.g., poly(isoprene).
  • the macrodiol and diisocyanate can be combined with a chain extender that includes a compound of Formula (6a): [Formula (6a)], wherein X 6 is O or NH; X 7 is O or NH; R 6* is a C2-30 aromatic group.
  • the C6-30 aromatic group refers to a divalent fragment in which each carbon atom in the shortest sequence of atoms from X 6 to X 7 is part of an aromatic system. Such systems may include sp 3 hybridized carbons, so long as such carbons are not part of the shortest path from X 6 to X 7 .
  • the polyurethane may then be combined with a chain connecter that includes a compound of Formula (7a): [Formula (7a)], 8 X is O or NH; X 9 is O or NH; R 7* is an unsaturated C 2-30 group.
  • X 8 and X 9 are both O, and R 7* is an unsaturated C 4-10 group having a single unsaturated carbon-carbon bond. Exemplary R 7* groups include: or point of attachment to X 9 .
  • the polyurethane is not combined with a chain connector.
  • the chain connector may be present in an amount that is from 1-99% relative to polyurethane. In this context, the ratio refers to the mass of the polyurethane and the chain connector.
  • the polyurethane can be present in an amount that is from 1-25%, from 10-25%, from 25-50%, from 50-75%, from 75-99%, or from 90-99%, relative to chain connector. In some implementations, the polyurethane can be present in an amount that is 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 85% relative to the chain connector. [0388] In some implementations, the polyurethane can be present in an amount from 90- 99.99%, from 90-95%, from 95-99%, from 95-97%, from 97-99%, or from 98-99%, relative to the chain connector.
  • the polyurethane can be present in an amount that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% relative to the chain connector.
  • the disclosed herein polyurethanes can have a different degree of branching.
  • the degree of branching of the polyurethanes can be varied from 0 to 99 % of the total polymer composition, including exemplary values of 0.5 %, 1 %, 5 %, 10 %, 15 %, 20 %, 25 %, 30 %, 35 %, 40 %, 45 %, 50 %, 55 %, 60 %, 65 %, 70 %, 75 %, 80 %, 85 %, 90 %, and 95 %.
  • the degree of branching of the disclosed herein polyurethanes is from 0 to 20 %, including exemplary values of 1 %, 2 %, 3 %, 4 %, 5 %, 6 %, 7 %, 8 %, 9 %, 10 %, 11 %, 12 %, 13 %, 14 %, 15 %, 16 %, 17 %, 18 % and 19 %.
  • the lower degree of branching can make the polyurethane more crystalline and thus enhance the tensile strength and hence biostability of the polyurethane.
  • compositions disclosed herein can also comprise pharmaceutically active ingredients.
  • pharmaceutically active ingredients refers to the components that have a pharmaceutical activity that can affect the subject’s body performance. It is understood that the terms “pharmaceutically active ingredients,” “therapeutic agents,” “drugs,” and “medicine” are used interchangeably.
  • the compositions disclosed herein comprise one or more pharmaceutically active ingredients.
  • the one or more pharmaceutically active ingredients can be included as a coating of the component formed from the disclosed herein polymer composition, or within (e.g., blended with) the polymer composition, or attached to (e.g., covalently or non-covalently bound to) polymer composition.
  • a wide variety of pharmaceutically active ingredients can be employed, including those used for the treatment of a wide variety of diseases and conditions (i.e., the prevention of a disease or condition, the reduction or elimination of symptoms associated with a disease or condition, or the substantial or complete elimination of a disease or condition).
  • the exemplary the pharmaceutically active ingredients can include but are not limited to (a) anti-thrombotic agents such as heparin, heparin derivatives, urokinase, clopidogrel, and PPack (dextrophenylalanine proline arginine chloromethylketone); (b) anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine and mesalamine; (c) antineoplastic/antiproliferative/anti-miotic agents such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin, angiopeptin, monoclonal antibodies capable of blocking smooth muscle cell proliferation, and thymidine kinase inhibitors; (d) anesthetic agents such as lidocaine,
  • Typical pharmaceutically active ingredient loadings range, for example, from 0.001 wt.% to 25 wt.% of the total polymer composition, including exemplary values of 0.005 wt.%, 0.01 wt.%, 0.05 wt.%, 0.1 wt.%, 0.5 wt.%, 1 wt.%, 2 wt.%, 3 wt.%, 4 wt.%, 5 wt.%, 6 wt.%, 7 wt.%, 8 wt.%, 9 wt.%, 10 wt.%, 11 wt.%, 12 wt.%, 13 wt.%, 14 wt.%, 15 wt.%, 16 wt.%, 17 wt.%, 18 wt.%, 19 wt.%, 20 wt.%,
  • the disclosed herein materials are engineered to provide improved biostability, fatigue resistance and the desired flexibility, elasticity and softness that can be used in insertable and implantable medical devices.
  • the polymeric materials disclosed herein can be extruded as films, coatings, fibers, or any combination thereof.
  • the polymeric materials disclosed herein can be extruded into any desired shape or form.
  • the polymeric materials disclosed herein can be molded to any desired shape or form.
  • the disclosed herein compositions can be used for electrospinning of the fibers.
  • the devices disclosed herein can have at least a portion comprising any of the disclosed herein polymeric compositions.
  • a substantial portion of the medical device can comprise any of the disclosed herein polymeric compositions.
  • the devices disclosed herein and comprising any of the disclosed herein compositions are insertable and/or implantable medical devices.
  • the devices disclosed herein are implantable medical devices that are configured to stay in a subject’s body for a predetermined period of time without substantially changing.
  • the predetermined period of time is greater than one week, greater than 1 month, greater than 6 months, greater than 1 year, greater than 5 years, greater than 10 years, greater than 15 years, greater than 20 years, greater than 30 years, greater than 40 years or even greater than 50 years.
  • the predetermined period of time is at least 1 day, at least 1 week, at least 1 month, at least 6 months, at least 1 year, at least 5 years, at least 10 years, at least 15 years, or at least 20 years.
  • the device comprising any of the disclosed herein composition are implantable heart valves.
  • FIG.1 shows a prosthetic heart valve 10, according to one aspect.
  • the illustrated prosthetic valve is adapted to be implanted in the native aortic annulus, although in other aspects, it can be adapted to be implanted in the other native annuluses of the heart (e.g., the pulmonary, mitral, and tricuspid valves).
  • the prosthetic valve can also be adapted to be implanted in other tubular organs or passageways in the body.
  • the prosthetic valve 10 can have four main components: a stent or frame 12, a valvular structure 14, an inner skirt 16, and an exemplary perivalvular outer sealing member or outer skirt 18.
  • the exemplary prosthetic valve 10 has an inflow end portion 15, an intermediate portion 17, and an outflow end portion 19.
  • the outer sealing member 18 has a proximal end 1802 and a distal end 1804 and is mounted circumferentially around a first portion of the outer surface of the annular frame 12, wherein the first portion 1806 of the outer surface has a proximal end and a distal end, wherein the proximal end of the first portion is at the inflow end 15 of the annular frame 12.
  • the first portion 1806 of the annular frame can be between the inflow end 15 of the annular frame and the beginning of the intermediate portion 17.
  • the first portion, 1806, is also defined by a proximal end 1806a and a distal end 1806b.
  • the annular frame also has a second portion 1820 that is free of the outer sealing member and extends between the outflow end 19 of the annular frame and the distal end of the first portion 1806b.
  • the bare frame 12 is shown in FIG.2.
  • Frame 12 can be formed with a plurality of circumferentially spaced slots or commissure windows, 20 (three are shown in the illustrated and unlimiting aspect) that are adapted to mount the commissures of the valvular structure 14 to the frame, as described in greater detail below.
  • the frame 12 can be made of any of various suitable plastically-expandable materials (e.g., stainless steel, etc.) or self- expanding materials (e.g., nickel-titanium alloy (NiTi), such as nitinol) as known in the art.
  • frame 12 When constructed of a plastically-expandable material, frame 12 (and thus the prosthetic valve 10) can be crimped to a radially collapsed configuration on a delivery catheter and then expanded at the implantation site by an inflatable balloon or equivalent expansion mechanism.
  • frame 12 When constructed of a self-expandable material, frame 12 (and thus the prosthetic valve 10) can be crimped to a radially collapsed configuration and restrained in the collapsed configuration by insertion into a sheath or equivalent mechanism of a delivery catheter. Once inside the body, the prosthetic valve can be advanced from the delivery sheath, which allows the prosthetic valve to expand to its functional size.
  • Suitable plastically-expandable materials that can be used to form the frame 12 include, without limitation, stainless steel, biocompatible, high-strength alloys (e.g., a cobalt-chromium or nickel-cobalt-chromium alloys), polymers, or combinations thereof.
  • frame 12 is made of a nickel-cobalt-chromium-molybdenum alloy, such as MP35N® alloy (SPS Technologies, Jenkintown, Pa.), which is equivalent to UNS R30035 alloy (covered by ASTM F562-02).
  • MP35N® alloy/UNS R30035 alloy comprises 35% nickel, 35% cobalt, 20% chromium, and 10% molybdenum by weight. It has been found that the use of MP35N® alloy to form frame 12 provides superior structural results over stainless steel. In particular, when MP35N® alloy is used as the frame material, less material is needed to achieve the same or better performance in radial and crush force resistance, fatigue resistance, and corrosion resistance.
  • frame 12 in the illustrated aspect comprises a first, lower row I of angled struts 22 arranged end-to-end and extending circumferentially at the inflow end of the frame; a second row II of circumferentially extending angled struts 24; a third row III of circumferentially extending, angled struts 26; a fourth row IV of circumferentially extending angled struts 28; and a fifth row V of circumferentially extending, angled struts 32 at the outflow end of the frame.
  • a plurality of substantially straight axially extending struts 34 can be used to interconnect the struts 22 of the first row I with the struts 24 of the second row II.
  • the fifth row V of angled struts 32 are connected to the fourth row IV of angled struts 28 by a plurality of axially extending window frame portions 30 (which define the commissure windows 20) and a plurality of axially extending struts 31.
  • Each axial strut 31 and each frame portion 30 extends from a location defined by the convergence of the lower ends of two angled struts 32 to another location defined by the convergence of the upper ends of two angled struts 28.
  • Each commissure window frame portion 30 mounts a respective commissure of the leaflet structure 14. As can be seen, each frame portion 30 is secured at its upper and lower ends to the adjacent rows of struts to provide a robust configuration that enhances fatigue resistance under cyclic loading of the prosthetic valve compared to known, cantilevered struts for supporting the commissures of the leaflet structure. This configuration enables a reduction in the frame wall thickness to achieve a smaller crimped diameter of the prosthetic valve. In certain aspects, the thickness T of frame 12 (FIG.2) measured between the inner diameter and outer diameter is 0.48 mm or less. [0405] The struts and frame portions of the frame collectively define a plurality of open cells of the frame.
  • struts 22, struts 24, and struts 34 define a lower row of cells defining openings 36.
  • the second, third, and fourth rows of struts 24, 26, and 28 define two intermediate rows of cells defining openings 38.
  • the fourth and fifth rows of struts 28 and 32, along with frame portions 30 and struts 31, define an upper row of cells defining openings 41.
  • the openings 41 are relatively large and are sized to allow portions of the leaflet structure 14 to protrude, or bulge, into and/or through the openings 41 when the frame 12 is crimped in order to minimize the crimping profile.
  • Frame 12 is configured to reduce, prevent, or minimize possible over-expansion of the prosthetic valve at a predetermined balloon pressure, especially at the outflow end portion of the frame, which supports the leaflet structure 14.
  • the frame is configured to have relatively larger angles 42a, 42b, 42c, 42d, 42e between struts, as shown in FIG.3. The larger the angle, the greater the force required to open (expand) the frame.
  • the angles between the struts of the frame can be selected to limit the radial expansion of the frame at a given opening pressure (e.g., inflation pressure of the balloon).
  • these angles are at least 110 degrees or greater when the frame is expanded to its functional size, and even more particularly, these angles are up to 120 degrees when the frame is expanded to its functional size.
  • the inflow 15 and outflow 19 ends of a frame generally tend to over- expand more so than the middle portion of the frame due to the “dog-boning” effect of the balloon used to expand the prosthetic valve.
  • the leaflet structure desirably is secured to the frame 12 below the upper row of struts 32, as best shown in FIG.1.
  • the valvular structure 14 can comprise three leaflets 40 (FIG.4), collectively forming a leaflet structure, which can be arranged to collapse in a tricuspid arrangement.
  • the leaflets can be formed from the disclosed herein polymer compositions.
  • the polymer composition can exhibit a tensile strength from 30 MPa to 40 MPa, including exemplary values of 31 MPa, 32 MPa, 33 MPa, 34 MPa, 35 MPa, 36 MPa, 37 MPa, 38 MPa, and 39 MPa.
  • the leaflets can exhibit a tensile strength having any values between any foregoing values or within a range formed by any of the foregoing values.
  • the leaflets can exhibit a tensile strength from 30 MPa to 37 MPa, or 30 MPa to 35 MPa, or 30 MPa to 32 MPa, or 32 MPa to 40 MPa, and so on.
  • the leaflets formed from the disclosed herein compositions can have an elastic modulus from 15 MPa to 25 MPa, including exemplary values of 16 MPa, 17 MPa, 18 MPa, 19 MPa, 20 MPa, 21 MPa, 22 MPa, 23 MPa, and 24 MPa.
  • the leaflets can exhibit an elastic modulus having any values between any foregoing values.
  • the leaflets can exhibit the elastic modulus having any values between any foregoing values or within a range formed by any of the foregoing values.
  • the leaflets can exhibit a elastic modulus from 16 MPa to 24 MPa, or 16 MPa to 22 MPa, or 16 MPa to 20 MPa, or 16 MPa to 18 MPa, or 18 MPa to 25 MPa, and so on.
  • the leaflets formed from the disclosed herein compositions can exhibit elongation greater than 100%, greater than 200%, greater than 300%, greater than 400%, or greater 500%.
  • the leaflets formed from the disclosed herein compositions can exhibit elongation of at least 500%, at least 400%, at least 300%, or at least 100%.
  • the leaflets 40 of the leaflet structure 14 formed from the disclosed herein polymer composition can have an undulating, curved scalloped shape (suture line 154 shown in FIG. 6 tracks the scalloped shape of the leaflet structure).
  • suture line 154 shown in FIG. 6 tracks the scalloped shape of the leaflet structure.
  • portions of the leaflets can protrude longitudinally beyond the outflow end of the frame when the prosthetic valve is crimped if the leaflets are mounted too close to the distal end of the frame.
  • the delivery catheter on which the crimped prosthetic valve is mounted includes a pushing mechanism or stop member that pushes against or abuts the outflow end of the prosthetic valve (for example, to maintain the position of the crimped prosthetic valve on the delivery catheter), the pushing member or stop member can damage the portions of the exposed leaflets that extend beyond the outflow end of the frame.
  • the outflow end of the frame 12 rather than the leaflets 40 is the proximal-most component of the prosthetic valve 10.
  • the delivery catheter includes a pushing mechanism or stop member that pushes against or abuts the outflow end of the prosthetic valve, the pushing mechanism or stop member contacts the outflow end of the frame, and not leaflets 40, so as to avoid damage to the leaflets.
  • the openings 36 of the lowermost row of openings in the frame are relatively larger than the openings 38 of the two intermediate rows of openings.
  • frame 12 when crimped, to assume an overall tapered shape that tapers from a maximum diameter at the outflow end of the prosthetic valve to a minimum diameter at the inflow end of the prosthetic valve.
  • frame 12 has a reduced diameter region extending along a portion of the frame adjacent the inflow end of the frame that generally corresponds to the region of the frame covered by the outer skirt 18.
  • the reduced diameter region is reduced compared to the diameter of the upper portion of the frame (which is not covered by the outer skirt) such that the outer skirt 18 does not increase the overall crimp profile of the prosthetic valve.
  • the frame can expand to the generally cylindrical shape shown in FIG.3.
  • the frame of a 26-mm prosthetic valve when crimped, had a first diameter of 14 French at the outflow end of the prosthetic valve and a second diameter of 12 French at the inflow end of the prosthetic valve.
  • the polymer compositions disclosed herein can be used to form an inner skirt 16. It is understood that the inner skirt can be formed as a film of the desired thickness, or it can be used as a textile. It is understood that if the inner skirt is a textile material, this textile material can be woven or knitted. In certain aspects, the inner skirt is a woven textile. In such aspects, one or more warp yarns comprise one or more fibers comprising the disclosed herein composition.
  • one or more weft yarns can comprise one or more fibers comprising the disclosed herein composition.
  • one or more warp yarns and one or more weft yarns can comprise fibers comprising the disclosed herein composition.
  • the formed textiles and/or films can exhibit a tensile strength of 100 MPa to 200 MPa, including exemplary values of 110 MPa, 120 MPa, 130 MPa, 140 MPa, 150 MPa, 160 MPa, 170 MPa, 180 MPa, and 190 MPa.
  • the formed textiles and/or films can exhibit a tensile strength having any values between any foregoing values or within a range formed by any of the foregoing values.
  • the formed textiles and/or films comprising the disclosed herein polymer compositions can exhibit a tensile strength from 100 MPa to 180 MPa, or 100 MPa to 150 MPa, or 100 MPa to 130 MPa, or 140 MPa to 200 MPa, and so on.
  • the formed textiles and/or films can exhibit an elastic modulus from 50 MPa to 150 MPa, including exemplary values of 60 MPa, 70 MPa, 80 MPa, 90 MPa, 100 MPa, 110 MPa, 120 MPa, 130 MPa, and 140 MPa.
  • the formed textiles and/or films can exhibit an elastic modulus having any values between any foregoing values or within a range formed by any of the foregoing values.
  • the formed textiles and/or films comprising the disclosed herein polymer compositions can exhibit an elastic modulus from 50 MPa to 130 MPa, or 50 MPa to 100 MPa, or 50 MPa to 80 MPa, or 70 MPa to 150 MPa, and so on.
  • the formed textiles and/or films can exhibit elongation of 100 % to 150 %, including exemplary values of 105 %, 110 %, 115 %, 120 %, 125 %, 130 %, 135 %, 140 %, and 145 %.
  • the formed textiles and/or films can exhibit elongation having any values between any foregoing values or within a range formed by any of the foregoing values.
  • the formed textiles and/or films comprising the disclosed herein polymer compositions can exhibit elongation from 100 % to 130 %, or 100 % to 135 %, 100 % to 120 % or 100 % to 110 %, or 110 % to 140 %, and so on.
  • the main functions of the inner skirt 16 are to assist in securing the valvular structure 14 to the frame 12 and to assist in forming a good seal between the prosthetic valve and the native annulus by blocking the flow of blood through the open cells of the frame 12 below the lower edge of the leaflets.
  • inner skirt 16 can have a variable thickness, for example, the skirt can be thicker at at least one of its edges than at its center.
  • inner skirt 16 can comprise a skirt formed from the disclosed herein compositions and having a thickness of 0.07 mm at its edges and 0.06 mm at its center. The thinner skirt can provide for better crimping performances while still providing good perivalvular sealing.
  • the inner skirt 16 can be secured to the inside of frame 12 via sutures 70, as shown in FIG.6.
  • Valvular structure 14 can be attached to the skirt via one or more reinforcing strips 72 (FIG.7) (which collectively can form a sleeve), for example, thin, PET reinforcing strips, discussed below, which enables a secure suturing and protects the pericardial tissue of the leaflet structure from tears.
  • Valvular structure 14 can be sandwiched between skirt 16 and the thin PET strips 72, as shown in FIG.7.
  • Sutures 154 which secure the PET strip and the leaflet structure 14 to skirt 16, can be any suitable suture, such as Ethibond Excel® PET suture (Johnson & Johnson, New Brunswick, N.J.). Sutures 154 desirably track the curvature of the bottom edge of leaflet structure 14, as described in more detail below.
  • the disclosed herein inner skirt is configured to be elastic enough such that when it elongates along with the frame, no deformation to the struts of the framer occurs, and a uniform crimping is obtained.
  • the inner skirt 16 can be sutured to frame 12 at locations away from the suture line 154 so that the skirt can be more pliable in that area. This configuration can avoid stress concentrations at the suture line 154, which attaches the lower edges of the leaflets to the inner skirt 16.
  • the leaflet structure 14 in the illustrated aspect includes three flexible leaflets 40 (although a greater or a smaller number of leaflets can be used).
  • the leaflets 40 can be secured to one another at their adjacent sides to form commissures 122 of the leaflet structure (FIG.6).
  • a plurality of flexible connectors 124 (one of which is shown in FIG.5) can be used to interconnect pairs of adjacent sides of the leaflets and to mount the leaflets to the commissure window frame portions 30 (FIG. 3).
  • FIG.5 shows the adjacent sides of two leaflets 40 interconnected by a flexible connector 124.
  • Three leaflets 40 can be secured to each other side-to-side using three flexible connectors 124, as shown in FIG.4. Additional information regarding connecting the leaflets to each other, as well as connecting the leaflets to the frame, can be found, for example, in U.S.
  • the inner skirt 16 can be used to assist in suturing the leaflet structure 14 to the frame.
  • the inner skirt 16 can have an undulating temporary marking suture to guide the attachment of the lower edges of each leaflet 40.
  • the inner skirt 16 itself can be sutured to the struts of frame 12 using sutures 70, as noted above, before securing the leaflet structure 14 to the skirt 16.
  • the struts that intersect the marking suture desirably are not attached to the inner skirt 16. This allows the inner skirt 16 to be more pliable in the areas not secured to the frame and minimizes stress concentrations along the suture line that secures the lower edges of the leaflets to the skirt.
  • the outer skirt 18 can comprise the disclosed herein compositions. While in other aspects, the outer skirt 18 does not comprise the disclosed herein compositions. In yet still further aspects, the outer skirt 18 can be constructed as known in the art applications, for example and without limitations similarly to the outer skirt disclosed in patent applications, WO/2018/222799 or WO/2006/005015, the entire descriptions of which are incorporated herein by reference. [0426] It is understood that the device disclosed above is only exemplary, and other medical devices can comprise the disclosed herein compositions.
  • the disclosed herein medical devices can comprise electrical simulations systems such as spinal cord stimulation (SCS) systems, deep brain stimulation (DBS) systems, peripheral nerve stimulation (PNS) systems, gastric nerve stimulation systems, cochlear implant systems, and retinal implant systems.
  • the devices can comprise cardiac systems, including implantable pacemaker systems, implantable cardioverter- defibrillators (ICD’s), and cardiac resynchronization and defibrillation (CRDT) devices.
  • the disclosed herein compositions can be included in polymeric components used for leads, including lead insulation, outer body insulation, and components for the foregoing implantable electrical stimulation systems.
  • compositions can be used in stents (including coronary vascular stents, peripheral vascular stents, cerebral, urethral, ureteral, biliary, tracheal, gastrointestinal and esophageal stents), stent coverings, stent-grafts.
  • stents including coronary vascular stents, peripheral vascular stents, cerebral, urethral, ureteral, biliary, tracheal, gastrointestinal and esophageal stents
  • stent coverings including coronary vascular stents, peripheral vascular stents, cerebral, urethral, ureteral, biliary, tracheal, gastrointestinal and esophageal stents
  • stent coverings including coronary vascular stents, peripheral vascular stents, cerebral, urethral, ureteral, biliary, tracheal, gastrointestinal and esophageal
  • compositions can be used to form abdominal aortic aneurysm (AAA) devices (e.g., AAA stents, AAA grafts, etc.), vascular access ports, dialysis ports, embolization devices including cerebral aneurysm filler coils (including Guglilmi detachable coils and metal coils) and the like.
  • AAA abdominal aortic aneurysm
  • the disclosed herein compositions can be used in embolic agents, tissue bulking devices, and catheters. It is understood that the term “catheter” can be used in a broad interpretation and include, without limitations, renal or vascular catheters such as balloon catheters and various central venous catheters.
  • compositions disclosed herein also can be used in introducers, guide wires, balloons, filters, septal defect closure devices, myocardial plugs, patches, Ventricular assist devices including left ventricular assist hearts and pumps, total artificial hearts, shunts, anastomosis clips and rings, and the like.
  • the disclosed herein compositions can also be utilized in tissue engineering as scaffolds for cartilage, bone, skin and other in vivo tissue regeneration (e.g., porous scaffolds, electrospun films and membranes for tissue integration), urethral slings, hernia "meshes, artificial ligaments, orthopedic prosthesis, one graft, or spinal disks.
  • the disclosed herein compositions can be used in dental implants.
  • compositions disclosed herein can constitute at least one component of any of the disclosed herein devices or the device can be substantially constructed of the disclosed herein compositions. It is further understood that the component constitutes both a coating and a specific element of the device. When the compositions disclosed herein are used as a coating, they coat any other materials present in the device, for example, metals, other polymers, ceramics, or any combinations thereof.
  • EXAMPLE 1 To obtain the disclosed herein polyurethane compositions, a saturated polyol of MW 1500-3000 Daltons is combined with any of the disclosed herein chain extenders at room temperature and then degassed under vacuum (2 torrs). Any of the disclosed herein diisocyanates is then added, and the mixture is mixed vigorously at high temperatures (75 °C to 95 °C) under atmospheric pressure for a few hours (3 hrs – 8 hrs). Any of the disclosed herein chain connectors (crosslinkers) can then be added. The reaction is cooled to a lower temperature (40 °C to 60 °C) for a few minutes (10-20 mins). Then the mixture is cooled to room temperature and left for 24-48 hrs.
  • EXAMPLARY ASPECTS [0430] EXEMPLARY ASPECT 1.
  • the crosslinked polyurethane of any preceding exemplary aspects particularly Exemplary Aspect 1, wherein the polyurethane has a molecular weight from 50,000 g/mol to 1,000,000 g/mol.
  • EXEMPLARY ASPECT 3 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-2, wherein the polyurethane has a molecular weight that is from 100,000 g/mol to 300,000 g/mol.
  • crosslinked polyurethane of any preceding exemplary aspects particularly Exemplary Aspects 1-3, wherein the crosslinkable group comprises a carbon-carbon double bond, carbon-carbon triple bond, epoxide, carboxylic acid, activated carboxylic acids, a clickable group, or combination thereof.
  • EXEMPLARY ASPECT 5 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-4, wherein the crosslinkable group comprises a carbon-carbon double bond.
  • EXEMPLARY ASPECT 7 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-6, wherein the crosslinkable group comprises an epoxide.
  • EXEMPLARY ASPECT 8. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-7, wherein [soft] comprises a poly(alkenyl) component.
  • EXEMPLARY ASPECT 9. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-8, wherein [soft] comprises a poly(1,3- butadiene), poly(2,3-dimethyl-1,3-butadine), or poly(isoprene) component.
  • EXEMPLARY ASPECT 10 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-9, wherein [soft] comprises a poly(alkynyl) component.
  • EXEMPLARY ASPECT 11 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-10, wherein [soft] comprises a poly(alkyl) component, wherein the poly(alkyl) is not polyisobutylene.
  • EXEMPLARY ASPECT 12 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-11, wherein [soft] comprises a poly(ethylene) component.
  • EXEMPLARY ASPECT 13 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-11, wherein [soft] comprises a poly(ethylene) component.
  • EXEMPLARY ASPECT 14 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-13, wherein [soft] comprises a poly(isobutylene-co-isoprene) component.
  • EXEMPLARY ASPECT 15 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-14, wherein the poly(isobutylene-co- isoprene) component is a block copolymer. [0445] EXEMPLARY ASPECT 16.
  • EXEMPLARY ASPECT 17 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-16, wherein [soft] comprises a poly(isobutylene-co-isoprene) component, wherein the isobutylene portion is present in an amount from 1-99 wt.% relative to the isoprene portion.
  • [soft] comprises a poly(isobutylene-co-ethylene) component.
  • EXEMPLARY ASPECT 19 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-18, wherein the poly(isobutylene-co- ethylene) component is a block copolymer with the poly(isobutylene) or poly(isobutylene-co- isoprene) portion.
  • EXEMPLARY ASPECT 20 is a block copolymer with the poly(isobutylene) or poly(isobutylene-co- isoprene
  • EXEMPLARY ASPECT 22 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-21, wherein [soft] comprises a poly(isobutylene-co-ethylene-co-isoprene) component.
  • EXEMPLARY ASPECT 23 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-22, wherein the poly(isobutylene-co- ethylene-co-isoprene) component is a block copolymer.
  • EXEMPLARY ASPECT 24 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-21, wherein [soft] comprises a poly(isobutylene-co-ethylene-co-isoprene) component.
  • the crosslinked polyurethane of any preceding exemplary aspects particularly Exemplary Aspects 1-23, wherein the poly(isobutylene-co- ethylene-co-isoprene) component is a random copolymer.
  • EXEMPLARY ASPECT 25 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-24, wherein [soft] comprises a poly(meth)acrylate component.
  • the poly(meth)acrylate component comprises an oligomer derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec-butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof.
  • EXEMPLARY ASPECT 28 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-27, wherein [soft] comprises a poly(siloxane) component.
  • EXEMPLARY ASPECT 29 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-28, wherein [soft] comprises a poly(siloxane) component in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion.
  • EXEMPLARY ASPECT 30 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-27, wherein [soft] comprises a poly(siloxane) component.
  • the crosslinked polyurethane of any preceding exemplary aspects particularly Exemplary Aspects 1-29, wherein [soft] comprises a poly(dimethylsiloxane), a poly(vinyl-methylsiloxane), or a poly(divinylsiloxane) component.
  • EXEMPLARY ASPECT 32 is
  • EXEMPLARY ASPECT 33 EXEMPLARY ASPECT 33.
  • EXEMPLARY ASPECT 35 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-34, wherein A 4 is ethylene or a mixture of (ethylene) and (propylene).
  • EXEMPLARY ASPECT 36 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-35, wherein A 2 is (1,3-butadiene), (2,3- dimethyl-1,3-butadine), (isoprene), or a combination thereof.
  • EXEMPLARY ASPECT 37 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-36, wherein A 2 is (isoprene).
  • EXEMPLARY ASPECT 38 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-37, wherein A 2 has the formula: . preceding exemplary aspects, particularly Exemplary Aspects 1-38, wherein A 5 is (dimethyl)siloxane.
  • EXEMPLARY ASPECT 40 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-39, wherein A 3 and A 6 are absent.
  • EXEMPLARY ASPECT 41 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-39, wherein A 3 and A 6 are absent.
  • [CE] includes segments of Formula (4): [Formula (4)], wherein the wavy lines represent points of attachment to [DI], X 1 is O or NH; X 2 is O or NH; and R 4 is a saturated C2-30 group. [0478] EXEMPLARY ASPECT 49.
  • R4 has the structure: *- (CH2)4aX 4a (CH2)4b- # , wherein * represents the point of attachment to X 1 and # represents the point of attachment to X 2 ;
  • X 4a is null, CHR 4a , C(R 4a ) 2 , O, NH, or NCH 3 ;
  • R 4a is independently C1-8alkyl; 4a is 0-12; and 4b is 0-12, wherein when X 4a is null, O, NH, or NCH3 the sum of 4a and 4b is at least 2, and when X 4a is CHR 4a or C(R 4a ) 2 the sum of 4a and 4b is at least 1.
  • EXEMPLARY ASPECT 50 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-49, wherein X 1 is O or NH, X 2 is NH, X 4a is O, 4a is 2-12, and 4b is 0. [0480] EXEMPLARY ASPECT 51. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-50, wherein 4a is 2-12, X 4a is null, and 4b is 0. [0481] EXEMPLARY ASPECT 52.
  • R 5 has the structure: *- (CH 2 ) 5a X 5a (CH 2 ) 5b - # , wherein * represents the point of attachment to X 3 and # represents the point of attachment to X 4 ;
  • EXEMPLARY ASPECT 57 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-56, wherein one of 5a and 5b is 1, and the other of 5a and 5b is 0, and X 5a is CHR 5a or C(R 5a )2.
  • EXEMPLARY ASPECT 58 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-56, wherein one of 5a and 5b is 1, and the other of 5a and 5b is 0, and X 5a is CHR 5a or C(R 5a )2.
  • EXEMPLARY ASPECT 66 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-65, wherein the crosslinking is conducted by heating, electron beam, or UV irradiation.
  • EXEMPLARY ASPECT 67 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-66, wherein the crosslinking is conducted in the absence of a crosslinker.
  • EXEMPLARY ASPECT 68 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-67, wherein the crosslinking is conducted in the presence of a crosslinker.
  • EXEMPLARY ASPECT 69 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-65, wherein the crosslinking is conducted by heating, electron beam, or UV irradiation.
  • EXEMPLARY ASPECT 67 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspect
  • a crosslinker selected from a C4-30 unsaturated group having at least two carbon-carbon double bonds, a C2-30 group having at least two azide groups, a C2-30 group having at least two amine or thiol groups.
  • EXEMPLARY ASPECT 71 The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-70, wherein the crosslinker is present in an amount of 0.01-5 wt.%, 0.1-5 wt.%, 0.5-5 wt.%, 1-5 wt.%, 2.5-5 wt.%, 0.01-1 wt.%, or 0.5-2 wt.%. [0501] EXEMPLARY ASPECT 72.
  • EXEMPLARY ASPECT 73 EXEMPLARY ASPECT 73.
  • EXEMPLARY ASPECT 74 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-74, wherein the macrodiol has an average molecular weight from 100-100,000 Da, from 100-50,000 Da, from 100-25,000 Da, from 100-10,000 Da, from 100-5,000 Da, from 100-2,500 Da, from 100-1,000 Da, from 100-500 Da, from 250-1,000 Da, from 500-1,000 Da, from 500-1,500 Da, from 1,000-2,000 Da, from 1,000-3,000 Da, from 1,000-5,000 Da, from 1,500-2,500 Da, from 1,500-3,000 Da, from 2,500-5,000 Da, from 2,500-10,000 Da, from 5,000-10,000 Da, from 10,000-25,000 Da, from 10,000-50,000 Da, from 25,000-50,000 Da, from 25,000-75,000 Da, or from 50,000-100,000 Da.
  • EXEMPLARY ASPECT 75 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-74, wherein the macrodiol comprises a poly(alkenyl) component.
  • EXEMPLARY ASPECT 76 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-75, wherein the macrodiol comprises poly(1,3-butadiene), poly(2,3-dimethyl-1,3-butadine), or poly(isoprene), preferably poly(isoprene).
  • EXEMPLARY ASPECT 77 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-74, wherein the macrodiol comprises a poly(alkenyl) component.
  • EXEMPLARY ASPECT 76 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-75, wherein the macrodiol comprises poly(1,3-butadiene), poly(2,3-dimethyl-1,3-butadine), or poly
  • EXEMPLARY ASPECT 81 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-80, wherein the macrodiol comprises a poly(ethylene) component.
  • EXEMPLARY ASPECT 82 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-81, wherein the macrodiol comprises a poly(isobutylene- co-isoprene) component.
  • EXEMPLARY ASPECT 83 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-79, wherein the macrodiol comprises a poly(alkyl) component, wherein the poly(alkyl) is not polyisobutylene.
  • the poly(meth)acrylate component comprises an oligomer derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec-butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof.
  • EXEMPLARY ASPECT 87 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-86, wherein the macrodiol comprises a poly(siloxane) component.
  • EXEMPLARY ASPECT 88 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-87, wherein the macrodiol comprises a poly(dimethylsiloxane) component.
  • EXEMPLARY ASPECT 89 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-86, wherein the macrodiol comprises a poly(dimethylsiloxane) component.
  • the macrodiol has the formula: HO-[-(A 1 )d- (A 2 )e-(A 3 )f-(A 4 )g-(A 5 )h-(A 6 )peg]-OH, wherein A 1 is (isobutylene), and d is 1-10,000; A 2 is a C 1-20 alkenyl, and e is 0-500; A 3 is a C 1-20 alkynyl, and f is 0-500; A 4 is a C 1-20 alkyl, and g is 0- 10,000; A 5 is a siloxane, and h is 0-10,000; A 6 is a polyethylene glycol, and peg is 0-10,000 wherein d, e, f, g, h, and peg represent the number of monomer units.
  • EXEMPLARY ASPECT 90 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-89, wherein the macrodiol has the formula: HO-[-(A 1 )d’- (A 2 ) e’ -(A 3 ) f’ -(A 4 ) g’ -(A 5 ) h’ -(A 6 ) peg’ ]-OH, wherein A 1 is (isobutylene), and d' is 1-99; A 2 is a C 1- 20alkenyl, and e' is 0-99; A 3 is a C1-20alkynyl,, and f' is 0-99; A 4 is a C1-20alkyl, and g' is 0-99; A 5 is a siloxane, and h' is 0-99; A 6 is a polyethylene glycol, and peg' is 0-99, wherein d' + e' + f' + g' +
  • EXEMPLARY ASPECT 91 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-90, wherein A 2 has the , . 92.
  • EXEMPLARY ASPECT 93 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-92, wherein the macrodiol comprises a polyisobutylene diol and a second diol that does not include a polyisobutylene component.
  • EXEMPLARY ASPECT 94 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-93, wherein the second diol is a polyethylene diol, a siloxane diol, a polyethylene diol, or a combination thereof.
  • EXEMPLARY ASPECT 95 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-92, wherein the macrodiol comprises a polyisobutylene diol and a second diol that does not include a polyisobutylene component.
  • the chain extender comprises a compound of Formula (4a): [Formula (4a)], wherein X 1 is O or NH; X 2 is O or NH; R 4* is a C2-30 saturated aliphatic group. [0531] EXEMPLARY ASPECT 102.
  • R 4 has the structure: *-(CH 2 ) 4a X 4a (CH 2 ) 4b - # , wherein * represents the point of attachment to X 1 and # represents the point of attachment to X 2 ;
  • X 4a is null, CHR 4a , C(R 4a ) 2 , O, NH, or NCH 3 ;
  • R 4a is independently C 1-8 alkyl; 4a is 0-12; and 4b is 0-12, wherein when X 4a is null, O, NH, or NCH3, the sum of 4a and 4b is at least 2, and when X 4a is CHR 4a, the sum of 4a and 4b is at least 1.
  • EXEMPLARY ASPECT 103 The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-102, wherein X 1 is O or NH, X 2 is NH, X 4a is O, 4a is 2-12, and 4b is 0. [0533] EXEMPLARY ASPECT 104. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-103, wherein 4a is 2-12, X 4a is null, and 4b is 0. [0534] EXEMPLARY ASPECT 105.
  • R 5* has the structure: *-(CH2)5aX 5a (CH2)5b- # , wherein * represents the point of attachment to X 3 and # represents the point of attachment to X 4 ;
  • EXEMPLARY ASPECT 119 A medical device comprising the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71.
  • EXEMPLARY ASPECT 120 The medical device of any preceding exemplary aspects, particularly Exemplary Aspect 119, wherein the medical device is an implantable heart valve.
  • EXEMPLARY ASPECT 121 EXEMPLARY ASPECT 121.
  • EXEMPLARY ASPECT 123 The medical device of any preceding exemplary aspects, particularly Exemplary Aspect 121 or 122, wherein the inner skirt comprises the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71.
  • EXEMPLARY ASPECT 124 The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 122-123, wherein the one or more leaflets exhibit a tensile strength of 20 MPa to 40 MPa.
  • EXEMPLARY ASPECT 125 The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 122-124, wherein the one or more leaflets exhibit an elastic modulus of 15 MPa to 25 MPa.
  • EXEMPLARY ASPECT126 The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 122-125, wherein the one or more leaflets exhibit an elongation greater than 300%.
  • EXEMPLARY ASPECT127 The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 123-126, wherein the inner skirt exhibits a tensile strength of 100 MPa to 200 MPa.
  • EXEMPLARY ASPECT 128 The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 123-126, wherein the inner skirt exhibits a tensile strength of 100 MPa to 200 MPa.
  • EXEMPLARY ASPECT 129 The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 123-128, wherein the inner skirt exhibits an elongation of 100% to 150 %.
  • EXEMPLARY ASPECT 130 The medical device of any preceding exemplary aspects, particularly Exemplary Aspect 122, wherein the medical device comprises one or more components of electrical simulations system, cardiac system, stents, grafts, scaffolds, catheters, vascular access ports, dialysis ports, dental implants, artificial ligaments, orthopedic prosthesis, or any combination there.
  • EXEMPLARY ASPECT 131 A film comprising the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71.
  • EXEMPLARY ASPECT 132 A fiber comprising the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71.
  • EXEMPLARY ASPECT 133 A yarn comprising one or more fibers of any preceding exemplary aspects, particularly Exemplary Aspect 132.
  • EXEMPLARY ASPECT 134 A textile comprising one or more yarns of any preceding exemplary aspects, particularly Exemplary Aspect 133.
  • EXEMPLARY ASPECT 136 A coating comprising the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71.
  • EXEMPLARY ASPECT 137 A medical device comprising the film of any preceding exemplary aspects, particularly Exemplary Aspect 131.
  • EXEMPLARY ASPECT 138 A medical device comprising the fiber of any preceding exemplary aspects, particularly Exemplary Aspect 132.
  • EXEMPLARY ASPECT 139 A medical device comprising the textile of any preceding exemplary aspects, particularly Exemplary Aspects 134 or 135.
  • EXEMPLARY ASPECT 140 A medical device comprising the coating of any preceding exemplary aspects, particularly Exemplary Aspect 136.
  • the compositions and methods of the appended claims are not limited in scope by the specific compositions and methods described herein, which are intended as illustrations of a few aspects of the claims, and any compositions and methods that are functionally equivalent are intended to fall within the scope of the claims.
  • Various modifications of the compositions and methods, in addition to those shown and described herein, are intended to fall within the scope of the appended claims. Further, while only certain representative compositions and method steps disclosed herein are specifically described, other combinations of the compositions and method steps also are intended to fall within the scope of the appended claims, even if not specifically recited.

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Abstract

Crosslinked polyurethanes and medical devices including components made of such crosslinked polyurethanes, are disclosed. The crosslinked polyurethanes may be obtained by crosslinking a polyurethane having the formula: wherein a is from 1-10,000; b is from 1-10,000; c is from 0-500; Rcap is a capping group; [soft] represents a macrodiol segment comprising a poly(isobutylene) component; [DI] represents a diisocyante component; [CE] represents a chain extender component; [CC] represents a chain connector component, wherein one or more of [soft], [DI], [CE], and [CC] comprises a crosslinkable group. Also disclosed are methods of making the same and devices comprising the same.

Description

LONG-TERM BIOSTABLE THERMOPLASTIC COMPOSITIONS AND MEDICAL DEVICES CONTAINING THE SAME CROSS-REFERENCE TO RELATED APPLICATION [001] This application claims the benefit of U.S. Provisional Application 63/484,157, filed February 9, 2023, the contents of which are hereby incorporated in its entirety. TECHNICAL FIELD [002] The disclosure is directed to biostable thermoplastics and medical devices containing the same. BACKGROUND [003] Polymers are being considered as the material for more and more components of medical devices because of their ability to be tailored per performance requirements and their ease of processing. For example, most of the polymeric components for structural heart implants are in the form of coated or stand-alone films, i.e., as parts with high aspect ratio shapes. The major requirements of these films are biostability, i.e., longevity against material degradation due to the reactions caused by in vivo environment; fatigue resistance as the device is subjected to the same movements as the part of the beating heart it is providing therapy; and specific requirements of flexibility, elasticity and softness of the film as a device component. [004] Some of the common implantable polymers belong to the polymer families of silicone rubber, fluoropolymers, polyethylenes, polypropylenes, polyacrylates, and standard polyurethanes, but none of them are promising candidates for the combined biostability, fatigue resistance and additional specific requirements for structural heart implants’ components. Among them, the polyurethane family of polymers is the most interesting because of the variety of approaches by which the polyurethane properties can be tuned. Polyisobutylene (PIB) based polyurethanes have been identified as polyurethanes with unprecedented chemical resistance. Polyurethanes, which comprise at least one PIB segment, are believed to possess enhanced biostability and biocompatibility as the PIB segment is highly resistant to in vivo degradation. But even PIB polyurethane presents the risk of not meeting the in vivo environment longevity (> 20 years) and fatigue resistance (> 800 million cycles) required for film-shaped components of structural heart implants. The challenge with PIB polyurethanes is the phase separation of hard segments that makes the material contain regions that are more susceptible to in vivo degradation. Moreover, polyurethane linkages still desire additional strength to meet the long-term biostability requirement of structural heart implant components. Additionally, further tunability of the PIB polyurethane may be required to meet the specific requirements depending on the type of film component. [005] These needs and others are at least partially satisfied by the present disclosure. SUMMARY [006] Aspects of the current disclosure are directed to a crosslinked polyurethane, said crosslinked polyurethane obtained by crosslinking a polyurethane having the formula: wherein a is from 1-10,000; b is from 1-10,000; c is from 0-500;
Figure imgf000003_0001
[soft] represents a macrodiol segment comprising a poly(isobutylene) component; [DI] represents a diisocyante component; [CE] represents a chain extender component; [CC] represents a chain connector component, wherein one or more of [soft], [DI], [CE], and [CC] comprises a crosslinkable group. [007] In certain aspects, disclosed is the crosslinked polyurethane, wherein the polyurethane has a molecular weight from 50,000 g/mol to 1,000,000 g/mol. [008] In some aspects, in addition, or in alternative to any of the preceding aspects, the polyurethane has a molecular weight that is from 100,000 g/mol to 300,000 g/mol. [009] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the crosslinkable group comprises a carbon-carbon double bond, carbon-carbon triple bond, epoxide, carboxylic acid, activated carboxylic acids, a clickable group, or combination thereof. [010] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the crosslinkable group comprises a carbon-carbon double bond. [011] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the crosslinkable group comprises a terminal alkyne, azide, or combination thereof. [012] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the crosslinkable group comprises an epoxide. [013] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(alkenyl) component. [014] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(1,3-butadiene), poly(2,3-dimethyl-1,3-butadiene), or poly(isoprene) component. [015] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(alkynyl) component. [016] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(alkyl) component, wherein the poly(alkyl) is not polyisobutylene. [017] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(ethylene) component. [018] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(ethylene glycol) component. [019] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(isobutylene-co- isoprene) component. [020] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the poly(isobutylene-co-isoprene) component is a block copolymer. [021] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the poly(isobutylene-co-isoprene) component is a random copolymer. [022] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(isobutylene-co- isoprene) component, wherein the isobutylene portion is present in an amount from 1-99 wt.% relative to the isoprene portion. [023] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(isobutylene-co- ethylene) component. [024] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the poly(isobutylene-co-ethylene) component is a block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [025] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the poly(isobutylene-co-ethylene) component is a random copolymer with the poly(isobutylene) or poly(isobutylene-co- isoprene) portion. [026] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(isobutylene-co- ethylene) component, wherein the poly(alkylene) portion is present in an amount of 1-99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [027] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(isobutylene-co- ethylene-co-isoprene) component. [028] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the poly(isobutylene-co-ethylene-co- isoprene) component is a block copolymer. [029] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the poly(isobutylene-co-ethylene-co- isoprene) component is a random copolymer. [030] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(meth)acrylate component. [031] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(meth)acrylate component, wherein the poly(meth)acrylate portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [032] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the poly(meth)acrylate component comprises an oligomer derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec-butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof. [033] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(siloxane) component. [034] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(siloxane) component in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene- co-isoprene) portion. [035] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a poly(dimethylsiloxane), a poly(vinyl-methylsiloxane), or a poly(divinylsiloxane) component. [036] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises a polyethylene glycol component. [037] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the polyethylene glycol component has a molecular weight (in Daltons) from 100-100,000, from 500-10,000, from 1,000-50,000, from 500-2,500, from 2,500-7,500, from 5,000-10,000, from 10,000-25,000, from 25,000-50,000, or from 50,000-100,000. [038] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises an oligomer having the formula: -[-(A1)d-(A2)e-(A3)f-(A4)g-(A5)h-(A6)peg]-, wherein A1 is (isobutylene), and d is 1-10,000; A2 is C4-20alkenyl, and e is 0-500; A3 is C4- 20alkynyl, and f is 0-500; A4 is C2-20alkyl, and g is 0-10,000; A5 is a siloxane, and h is 0- 10,000; A6 is a polyethylene glycol, and peg is 0-10,000; wherein d, e, f, g, h, and peg represent the number of monomer units. [039] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] comprises an oligomer having the formula: -[-(A1)d’-(A2)e’-(A3)f’-(A4)g’-(A5)h’-(A6)peg’]-, wherein A1, A2, A3, A4, A5, and A6 are as defined above, and d’ is 1-100; e’ is 0-99; f’ is 0- 99; g’ is 0-99; h’ is 0-99; and peg’ is 0-99, wherein d’ + e’ + f’ + g’ + h’ + peg’ = 100; and d’, e’, f’, g’, h’, and peg’ represent the wt.% of each component in the soft segment. [040] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein A4 is ethylene or a mixture of (ethylene) and (propylene). [041] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein A2 is (1,3-butadiene), (2,3-dimethyl-1,3- butadiene), (isoprene), or a combination thereof. [042] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein A2 is (isoprene). [043] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein A2 has the formula: . [044]
Figure imgf000007_0001
disclosed is the crosslinked polyurethane, wherein A5 is (dimethyl)siloxane. [045] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein A3 and A6 are absent. [046] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [soft] is an oligomer having the formula: -[isobutylenyl]i-[isoprenyl]m-[dimethylsiloxane]o-, or -[isobutylenyl]i-[isoprenyl]m-[ethylenyl]n-[ dimethylsiloxane]o-; wherein: i is 1-10,000; n is 1-10,000; m is 1-50; and o is 0-10,000. [047] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [DI] includes segments of Formula (1): [Formula (1)], wherein the wavy lines represent points of attachment to any of [soft], [CE], or [CC], wherein R1 is a saturated C2-30 group. [048] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein R1 has the formula: ,
Figure imgf000008_0001
disclosed is the crosslinked polyurethane, wherein [DI] includes segments of Formula (2): [Formula (2)], wherein the wavy lines
Figure imgf000008_0002
to any of [soft], [CE], or [CC], wherein R2 is an unsaturated C2-30 group. [050] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein R2 has the formula: , .
Figure imgf000008_0003
[051] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [DI] includes segments of Formula (3): [Formula (3)], wherein the wavy lines to any of [soft], [CE], or [CC], wherein R3
Figure imgf000009_0001
is a C6-30 aromatic group. [052] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein R3 has the formula: or
Figure imgf000009_0002
aspects, disclosed is the crosslinked polyurethane, wherein [CE] includes segments of Formula (4): [Formula (4)], wherein the wavy lines represent
Figure imgf000009_0003
to [DI], X1 is O or NH; X2 is O or NH; R4 is a saturated C2-30 group. [054] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein R4 has the structure: *-(CH2)4aX4a(CH2)4b-#, wherein * represents the point of attachment to X1 and # represents the point of attachment to X2; X4a is null, CHR4a, C(R4a)2, O, NH, or NCH3; R4a is independently C1-8alkyl; 4a is 0-12; and 4b is 0-12, wherein when X4a is null, O, NH, or NCH3 the sum of 4a and 4b is at least 2, and when X4a is CHR4a or C(R4a)2 the sum of 4a and 4b is at least 1. [055] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein X1 is O or NH, X2 is NH, X4a is O, 4a is 2- 12, and 4b is 0. [056] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein 4a is 2-12, X4a is null, and 4b is 0. [057] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein one of 4a and 4b is 1, and the other of 4a and 4b is 0, and X4a is CHR4a or C(R4a)2. [058] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein X4a is C(CH3)2. [059] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [CE] includes segments of Formula (5): X3 X4 R5 [Formula (5)], wherein the wavy lines represent t 3 4
Figure imgf000010_0001
o [DI], X is O or NH; X is O or NH; R5 is an unsaturated C2-30 group. [060] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein R5 has the structure: *-(CH2)5aX5a(CH2)5b-#, wherein * represents the point of attachment to X3 and # represents the point of attachment to X4; X5a is CHR5a, C(R5a)2, -CH=CH-, or -C≡C-, R5a is in each case independently a C2-12 group, wherein when two of R5a are present, at least one of R5a is an unsaturated C2-12 group; 5a is 0-12; and 5b is 0-12, wherein when X5a is CH=CH-, or -C≡C- then 5a is 1-12, and 5b is 1-12, and when X5a is CHR5a the sum of 5a and 5b is at least 1. [061] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein 5a is 1-12, including 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11; 5b is 1-12, including 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11, and X5a is -CH=CH-. [062] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein one of 5a and 5b is 1, and the other of 5a and 5b is 0, and X5a is CHR5a or C(R5a)2. [063] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein R5a is C2-4alkenyl. [064] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [CE] includes segments of Formula (6): [Formula (6)],
Figure imgf000010_0002
wherein the wavy lines represent points of attachment to [DI], X6 is O or NH; X7 is O or NH; R6 is a C6-30 aromatic group. [065] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein [CC] is a segment of Formula (7): [Formula (7)], wherein the wavy lines represent to [DI], X8 is O or NH; X9 is O or NH;
Figure imgf000011_0001
R7 is an unsaturated C2-30 group. [066] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein X8 and X9 are both O, and R7 is an unsaturated C4-10 group having a single unsaturated carbon-carbon bond. [067] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein R7 has the formula: ,
Figure imgf000011_0002
point of attachment to X9. [068] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein (Rcap) is independently selected from OH, COOH, or NH2. [069] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein (Rcap) is independently selected from a C1- 12 alkyl, C6-12 aryl, or C1-12 alkyl substituted one or more times by C6-12 aryl. [070] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein (Rcap) is independently selected from a C1- 12 haloalkyl, C6-12 haloaryl, C1-12 alkyl substituted one or more times by C6-12 haloaryl, or C1- 12 haloalkyl substituted one or more times by C6-12 haloaryl. [071] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the crosslinking is conducted by heating, electron beam, or UV irradiation. [072] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the crosslinking is conducted in the absence of a crosslinker. [073] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the crosslinking is conducted in the presence of a crosslinker. [074] The crosslinked polyurethane of any preceding claim, wherein the crosslinking is conducted in the presence of a crosslinker selected from a C4-30 unsaturated group having at least two carbon-carbon double bonds, a C2-30 group having at least two azide groups, a C2-30 group having at least two amine or thiol groups. [075] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the crosslinking is conducted in the presence of a crosslinker comprising diallylmethyl amine, divinylbenze, ethylene glycol diacrylate, polyoxyethylene bis(azide), diethylene glycol bis(azidoacetate), 1,6 diazidohexane, 4,4′-bis(azidomethyl)-1,1′-biphenyl, ethylene glycol diacrylate, poly(ethylene glycol) diacrylate, neopentyl glycol diacrylate, trimethylolpropane triacrylate, pentaerythritol triacrylate, glycerol propoxylate triacrylate, trimethylolpropane propoxylate triacrylate, trimethylolpropane ethoxylate triacrylate, pentaerythritol tetraacrylate, di(trimethylolpropane) tetraacrylate, divinylbenzene, divinyl sulfone, 1,4-butanediol divinyl ether, ethylene glycol divinyl ether, di- tri-, and poly-ethylene glycol divinyl ether, or a combination thereof. [076] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the crosslinked polyurethane, wherein the crosslinker is present in an amount of 0.01-5 wt.%, 0.1-5 wt.%, 0.5-5 wt.%, 1-5 wt.%, 2.5-5 wt.%, 0.01-1 wt.%, or 0.5-2 wt.%. [077] Also disclosed are aspects directed to a method of making the crosslinked polyurethane of any preceding claim, comprising preparing a polyurethane by a process comprising the steps: preparing a first mixture comprising a macrodiol and disocyanate to give a first polyurethane, wherein the macrodiol comprises a poly(isobutylene) component; optionally forming a second reaction mixture comprising a chain extender and the first polyurethane to give a second polyurethane; and crosslinking the first polyurethane or second polyurethane. [078] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the first reaction mixture comprises a chain extender. [079] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the macrodiol can have an average molecular weight from 100-100,000 Da, from 100-50,000 Da, from 100-25,000 Da, from 100-10,000 Da, from 100- 5,000 Da, from 100-2,500 Da, from 100-1,000 Da, from 100-500 Da, from 250-1,000 Da, from 500-1,000 Da, from 500-1,500 Da, from 1,000-2,000 Da, from 1,000-3,000 Da, from 1,000-5,000 Da, from 1,500-2,500 Da, from 1,500-3,000 Da, from 2,500-5,000 Da, from 2,500-10,000 Da, from 5,000-10,000 Da, from 10,000-25,000 Da, from 10,000-50,000 Da, from 25,000-50,000 Da, from 25,000-75,000 Da, or from 50,000-100,000 Da. [080] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the macrodiol comprises a poly(alkenyl) component. [081] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the macrodiol comprises poly(1,3-butadiene), poly(2,3- dimethyl-1,3-butadiene), or poly(isoprene), preferably poly(isoprene). [082] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the macrodiol comprises a poly(isoprene) component. [083] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the macrodiol comprises a poly(isobutylene-co-isoprene) random copolymer. [084] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the macrodiol comprises a poly(alkynyl) component. [085] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the macrodiol comprises a poly(alkyl) component, wherein the poly(alkyl) is not polyisobutylene. [086] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the macrodiol comprises a poly(ethylene) component. [087] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the macrodiol comprises a poly(isobutylene-co-isoprene) component. [088] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the macrodiol comprises a poly(isobutylene-co-ethylene) component. [089] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the macrodiol comprises a poly(isobutylene-co-ethylene-co- isoprene) component. [090] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the macrodiol comprises a poly(meth)acrylate component. [091] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the poly(meth)acrylate component comprises an oligomer derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec-butyl (meth)acrylate, isobutyl (meth)acrylate, 2- ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof. [092] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the macrodiol comprises a poly(siloxane) component. [093] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the macrodiol comprises a poly(dimethylsiloxane) component. [094] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the macrodiol has the formula: HO-[-(A1)d-(A2)e-(A3)f-(A4)g-(A5)h-(A6)peg]-OH, wherein A1 is (isobutylene), and d is 1-10,000; A2 is a C1-20alkenyl, and e is 0-500; A3 is a C1- 20alkynyl, and f is 0-500; A4 is a C1-20alkyl, and g is 0-10,000; A5 is a siloxane, and h is 0- 10,000; A6 is a polyethylene glycol, and peg is 0-10,000, wherein d, e, f, g, h, and peg represent the number of monomer units. [095] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the macrodiol has the formula: HO-[-(A1)d’-(A2)e’-(A3)f’-(A4)g’-(A5)h’-(A6)peg’]-OH, wherein A1 is (isobutylene), and d’ is 1-99; A2 is a C1-20alkenyl, and e’ is 0-99; A3 is a C1- 20alkynyl, and f’ is 0-99; A4 is a C1-20alkyl, and g’ is 0-99; A5 is a siloxane, and h’ is 0-99; A6 is a polyethylene glycol, and peg’ is 0-99, wherein d’ + e’ + f’ + g’ + h’ + peg’ = 100; and d’, e’, f’, g’, h’, and peg’ represent the wt.% of each component in the macrodiol. [096] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein A2 has the formula: .
Figure imgf000014_0001
[097] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the macrodiol has the formula: HO-[isobutylenyl]i-[isoprenyl]m-[dimethylsiloxane]o-OH; HO-[isobutylenyl]i-[isoprenyl]m-[ethylenyl]n-[ dimethylsiloxane]o-OH; wherein: i is 1-10,000; n is 1-10,000; m is 1-50; and o is 0-10,000. [098] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the macrodiol comprises a polyisobutylene diol and a second diol that does not include a polyisobutylene component. [099] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the second diol is a polyethylene diol, a siloxane diol, a polyethylene diol, or a combination thereof. [0100] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the diisocyanate comprises a compound of Formula (1a): [Formula (1a)], wherein R1* is a saturated
Figure imgf000015_0001
[0101] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein R1* has the formula: ,
Figure imgf000015_0002
[0102] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the diisocyanate comprises a compound of Formula (2a): [Formula (2a)], wherein R2* is an
Figure imgf000016_0001
[0103] In some aspects, in or to any of the preceding aspects, disclosed is the method, wherein R2* groups is: , . [0104] In
Figure imgf000016_0002
aspects, disclosed is the method, wherein the diisocyanate comprises a compound of Formula (3a): [Formula (3a)], wherein R3* is a C6-30
Figure imgf000016_0003
[0105] T In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein R3* has the formula: or
Figure imgf000016_0004
aspects, disclosed is the method, wherein the chain extender comprises a compound of Formula (4a): [Formula (4a)], wherein X1 is O or NH; X2 is O
Figure imgf000016_0005
30 saturated aliphatic group. [0107] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein R4 has the structure: *-(CH2)4aX4a(CH2)4b-#, wherein * represents the point of attachment to X1 and # represents the point of attachment to X2; X4a is null, CHR4a, C(R4a)2, O, NH, or NCH3; R4a is independently C1-8alkyl; 4a is 0-12; and 4b is 0-12, wherein when X4a is null, O, NH, or NCH3 the sum of 4a and 4b is at least 2, and when X4a is CHR4a the sum of 4a and 4b is at least 1. [0108] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein X1 is O or NH, X2 is NH, X4a is O, 4a is 2-12, and 4b is 0. [0109] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein 4a is 2-12, X4a is null, and 4b is 0. [0110] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein one of 4a and 4b is 1, and the other of 4a and 4b is 0, and X4a is CHR4a or C(R4a)2. [0111] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein X4a is C(CH3)2. [0112] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the chain extender comprises a compound of Formula (5a): [Formula (5a)], X3 is O or NH; X4 is O or NH;
Figure imgf000017_0001
aliphatic group. [0113] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein R5* has the structure: *-(CH2)5aX5a(CH2)5b-#, wherein * represents the point of attachment to X3 and # represents the point of attachment to X4; X5a is CHR5a, C(R5a)2, -CH=CH-, or -C≡C-; R5a is in each case independently a C2-12 group, wherein when two of R5a are present, at least one of R5a is an unsaturated C2-12 group; 5a is 0-12; 5b is 0-12, wherein when X5a is CH=CH-, or -C≡C- then 5a is 1-12, and 5b is 1- 12, and when X5a is CHR5a the sum of 5a and 5b is at least 1. [0114] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein X3 is O or NH, X4 is NH, X5a is O, and 5b is 0. [0115] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein 5a is 1-12, 5b is 1-12, and X5a is -CH=CH- or -C≡C. [0116] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, one of 5a and 5b is 1, and the other of 5a and 5b is 0, and X5a is CHR5a or C(R5a)2. [0117] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein R5a is C2-4alkenyl. [0118] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the chain extender comprises a compound of Formula (6a): [Formula (6a)], X6 is O or NH; X7 is O or NH; R6* is a C2-30 aromatic group. [0119] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the chain connector comprises a compound of Formula (7a): [Formula (7a)], X8 is O or NH; X9 is O or NH; R7* is an unsaturated C2-30 group. [0120] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein X8 and X9 are both O, and R7* is an unsaturated C4-10 group having a single unsaturated carbon-carbon bond. [0121] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein R7* has the formula: or
Figure imgf000018_0001
point of attachment to X9. [0122] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method wherein the polyurethane is not combined with a chain connector. [0123] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is the method, wherein the polyurethane is combined with a chain connector in an amount that is from 1-99% relative to polyurethane. [0124] Also disclosed are aspects directed to a medical device comprising the crosslinked polyurethane of any of the disclosed herein aspects. [0125] In still further aspects, the medical device is an implantable heart valve. [0126] In some aspects, in addition, or in alternative to any of the preceding aspects, the disclosed medical device comprises an annular frame comprising an inflow end and an outflow end and being radially compressible and expandable between a radially compressed configuration and a radially expanded configuration; a leaflet structure comprising one or more leaflets and positioned with the frame and secured thereto; and an inner skirt mounted inside of the frame, wherein at least one of the one or more leaflets or the inner skirt comprises any of the disclosed herein crosslinked polyurethanes. [0127] In some aspects, in addition, or in alternative to any of the preceding aspects, the one or more leaflets comprise any of the disclosed herein crosslinked polyurethanes. [0128] In some aspects, in addition, or in alternative to any of the preceding aspects, the inner skirt comprises any of the disclosed herein crosslinked polyurethanes. [0129] In some aspects, in addition, or in alternative to any of the preceding aspects, the one or more leaflets exhibit a tensile strength of 20 MPa to 40 MPa. [0130] In some aspects, in addition, or in alternative to any of the preceding aspects, the one or more leaflets exhibit an elastic modulus of 15 MPa to 25 MPa. [0131] In some aspects, in addition, or in alternative to any of the preceding aspects, the one or more leaflets exhibit an elongation greater than 300%. [0132] In some aspects, in addition, or in alternative to any of the preceding aspects, the inner skirt exhibits a tensile strength of 100 MPa to 200 MPa. [0133] In some aspects, in addition, or in alternative to any of the preceding aspects, the inner skirt exhibits an elastic modulus of 50 MPa to 150 MPa. [0134] In some aspects, in addition, or in alternative to any of the preceding aspects, the inner skirt exhibits an elongation of 100% to 150 %. [0135] In some aspects, in addition, or in alternative to any of the preceding aspects, the disclosed medical device comprises one or more components of electrical simulations system, cardiac system, stents, grafts, scaffolds, catheters, vascular access ports, dialysis ports, dental implants, artificial ligaments, orthopedic prosthesis, or any combination there. [0136] Also disclosed are films comprising any of the disclosed herein crosslinked polyurethanes. [0137] Also disclosed are fibers comprising any of the disclosed herein crosslinked polyurethanes. [0138] In some aspects, in addition, or in alternative to any of the preceding aspects, disclosed is a yarn comprising any of the disclosed herein fibers. [0139] In some aspects, in addition, or in alternative to any of the preceding aspects disclosed is a textile comprising any of the disclosed herein yarns. In some aspects, the textile is woven or knitted. [0140] Also disclosed is a coating comprising any of the disclosed herein crosslinked polyurethanes. [0141] In some aspects, disclosed is a medical device comprising any of the disclosed herein films. In some aspects, in addition, or in alternative to any of the preceding aspects disclosed is a medical device comprising any of the disclosed herein fibers. In addition or in alternative to any of the preceding aspects disclosed is a medical device comprising any of the disclosed herein textiles. In addition or in alternative to any of the preceding aspects disclosed is a medical device comprising any of the disclosed herein coatings. BRIEF DESCRIPTION OF THE FIGURES [0142] FIGURE 1 is a perspective view of a prosthetic heart valve, according to one embodiment. [0143] FIGURES 2-3 show an exemplary frame of the prosthetic heart valve of FIG.1. [0144] FIGURES 4-5 show the assembly of an exemplary leaflet structure. [0145] FIGURES 6-7 show the assembly of the leaflet structure with the inner skirt along a lower edge of the leaflets. DETAILED DESCRIPTION [0146] Before the present methods and systems are disclosed and described, it is to be understood that the methods and systems are not limited to specific synthetic methods, specific components, or to particular compositions. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. [0147] The following description is provided as an enabling teaching of the disclosure in its best, currently known aspect. To this end, those skilled in the relevant art will recognize and appreciate that many changes can be made to the various aspects of the disclosure described herein while still obtaining the beneficial results of the present disclosure. It will also be apparent that some of the desired benefits of the present disclosure can be obtained by selecting some of the features of the present disclosure without utilizing other features. Accordingly, those of ordinary skill in the pertinent art will recognize that many modifications and adaptations to the present disclosure are possible and may even be desirable in certain circumstances and are a part of the present disclosure. Thus, the following description is again provided as illustrative of the principles of the present disclosure and not in limitation thereof. DEFINITIONS [0148] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In this specification and in the claims which follow, reference will be made to a number of terms that shall be defined herein. [0149] It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate aspects, can also be provided in combination in a single aspect. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single aspect, can also be provided separately or in any suitable subcombination. [001] As used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, a reference to “a monomer” includes two or more monomers, and a reference to “a device” includes two or more such devices and the like. [0150] Ranges may be expressed herein as from “about” one particular value and/or to “about” another particular value. When such a range is expressed, another aspect includesfrom the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint and independently of the other endpoint. [0151] “Optional” or “optionally” means that the subsequently described event or circumstance may or may not occur and that the description includes instances where said event or circumstance occurs and instances where it does not. [0152] Throughout the description and claims of this specification, the word “comprise” and variations of the word, such as “comprising” and “comprises,” means “including but not limited to,” and is not intended to exclude, for example, other additives, components, integers or steps. As used in the specification and in the claims, the term “comprising” can also include the aspects “consisting of” and “consisting essentially of.” [0153] For the terms "for example" and "such as" and grammatical equivalences thereof, the phrase "and without limitation" is understood to follow unless explicitly stated otherwise. It is further understood that these phrases are used for explanatory purposes only. “Exemplary” means “an example of” and is not intended to convey an indication of a preferred or ideal aspect. “Such as” is not used in a restrictive sense but for explanatory purposes. [0154] The term “or” means “and/or.” Recitation of ranges of values is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. The endpoints of all ranges are included within the range and independently combinable. All methods described herein can be performed in a suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. [0155] Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value recited or falling within the range unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited. The ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 or sub- ranges from the group consisting of 10-40, 20-50, 5-35, etc. Similarly, numerical ranges recited herein by endpoints include subranges subsumed within that range (e.g., 1 to 5 includes 1-1.5, 1.5-2, 2-2.75, 2.75-3, 3-3.90, 3.90-4, 4-4.24, 4.24-5, 2-5, 3-5, 1-4, and 2-4). [0156] A weight percent (wt. %) of a component, unless specifically stated to the contrary, is based on the total weight of the formulation or composition in which the component is included. [0157] Further, the terms “coupled” and “associated” generally mean electrically, electromagnetically, and/or physically (e.g., mechanically or chemically) coupled or linked and do not exclude the presence of intermediate elements between the coupled or associated items. [0158] It will be understood that when an element is referred to as being "connected" or "coupled" to another element, it can be directly connected or coupled to the other element, or intervening elements may be present. In contrast, when an element is referred to as being "directly connected" or "directly coupled" to another element, there are no intervening elements present. Other words used to describe the relationship between elements or layers should be interpreted in a like fashion (e.g., "between" versus "directly between," "adjacent" versus "directly adjacent," "on" versus "directly on"). As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items. [0159] It will be understood that although the terms "first," "second," etc., may be used herein to describe various elements, components, regions, layers, and/or sections. These elements, components, regions, layers, and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer, or section from another element, component, region, layer, or section. Thus, a first element, component, region, layer, or section discussed below could be termed a second element, component, region, layer, or section without departing from the teachings of exemplary aspects. [0160] Spatially relative terms, such as "beneath," "below," "lower," "above," "upper," and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as "below" or "beneath" other elements or features would then be oriented "above" the other elements or features. Thus, the term "below" can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations), and the spatially relative descriptors used herein are interpreted accordingly. [0161] As used herein, the term "substantially" means that the subsequently described event or circumstance completely occurs or that the subsequently described event or circumstance generally, typically, or approximately occurs. [0162] Still further, the term “substantially” can in some aspects, refer to at least 80 %, at least 85 %, at least 90 %, at least 91 %, at least 92 %, at least 93 %, at least 94 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least 99 %, or 100 % of the stated property, component, composition, or other condition for which substantially is used to characterize or otherwise quantify an amount. [0163] In other aspects, as used herein, the term “substantially free,” when used in the context of a composition or component of a composition that is substantially absent, is intended to indicate that the recited component is not intentionally batched and added to the composition but can be present as an impurity along with other components being added to the composition. In such aspects, the term “substantially free” is intended to refer to trace amounts that can be present in the batched components, for example, it can be present in an amount that is less than 1 % by weight, e.g., less than 0.5 % by weight, less than 0.1 % by weight, less than 0.05 % by weight, or less than 0.01 % by weight of the stated material, based on the total weight of the composition. [0164] As used herein, the term “substantially,” in, for example, the context “substantially identical” or “substantially similar,” refers to a method or a system, or a component that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% by similar to the method, system, or the component it is compared to. [0165] As used herein, the term or phrase “effective,” “effective amount,” or “conditions effective to” refers to such amount or condition that is capable of performing the function or property for which an effective amount or condition is expressed. As will be pointed out below, the exact amount or particular condition required will vary from one aspect to another, depending on recognized variables such as the materials employed and the processing conditions observed. Thus, it is not always possible to specify an exact “effective amount” or “condition effective to.” However, it should be understood that an appropriate effective amount will be readily determined by one of ordinary skill in the art using only routine experimentation. Although the operations of exemplary aspects of the disclosed method may be described in a particular sequential order for convenient presentation, it should be understood that disclosed aspects can encompass an order of operations other than the particular sequential order disclosed. For example, operations described sequentially may, in some cases, be rearranged or performed concurrently. Further, descriptions and disclosures provided in association with one particular aspect are not limited to that aspect and may be applied to any aspect disclosed. [0166] Moreover, for the sake of simplicity, the attached figures may not show the various ways (readily discernable, based on this disclosure, by one of ordinary skill in the art) in which the disclosed system, method, and apparatus can be used in combination with other systems, methods, and apparatuses. Additionally, the description sometimes uses terms such as “produce” and “provide” to describe the disclosed method. These terms are high-level abstractions of the actual operations that can be performed. The actual operations that correspond to these terms can vary depending on the particular implementation and are, based on this disclosure, readily discernible by one of ordinary skill in the art. [0167] Disclosed are components that can be used to perform the disclosed methods and systems. These and other components are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these components are disclosed that while specific reference of each various individual and collective combinations and permutation of these may not be explicitly disclosed, each is specifically contemplated and described herein, for all methods and systems. This applies to all aspects of this application, including, but not limited to, steps in disclosed methods. Thus, if there are a variety of additional steps that can be performed, it is understood that each of these additional steps can be performed with any specific aspect or combination of aspects of the disclosed methods. [0168] Compounds described herein can comprise one or more asymmetric centers and thus can exist in various stereoisomeric forms, e.g., enantiomers and/or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions, Wiley Interscience, New York, 1981; Wilen et al., Tetrahedron 33:2725 (1977); Eliel, E.L. Stereochemistry of Carbon Compounds, McGraw-Hill, NY, 1962; and Wilen, S.H., Tables of Resolving Agents and Optical Resolutions p.268, E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972. The disclosure additionally encompasses compounds as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers. [0169] The term “Cxx group” wherein xx is any number or range of numbers, refers to an organic fragment having the designated number of carbons. Unless specified to the contrary, the group may include one or more heteroatoms, so long as the specified number of carbon atoms is present. The fragment may be a substituent or may represent a linking group connecting two or more other groups. Unless specified to the contrary, a group may be unsubstituted or substituted as defined herein. By way of example, a C4 group includes (but is not limited to) the following fragments: . [0170]
Figure imgf000026_0001
with the further requirement that the group include one or more non-aromatic carbon-carbon double bonds or carbon-carbon triple bonds. By way of example, a C4-30 unsaturated group includes (but is not limited to) the following fragments: . [0171] The term
Figure imgf000026_0002
Cxx group, with the further requirement that the group does not include any non-aromatic carbon-carbon double bonds or carbon-carbon triple bonds. A “saturated Cxx group” may include one or more aromatic systems, so long as at least one sp3 hybridized carbon atoms is present. By way of example, a C4-30 saturated group includes (but is not limited to) the following fragments:
. [0172] Wh e and sub- range within the range. For example, "C1-6 alkyl" is intended to encompass C1, C2, C3, C4, C5, C6, C1-6, C1-5, C1-4, C1-3, C1-2, C2-6, C2-5, C2-4, C2-3, C3-6, C3-5, C3-4, C4-6, C4-5, and C5-6 alkyl. [0173] The term "alkyl" refers to a radical of a straight-chain or branched hydrocarbon group having a specified range of carbon atoms (e.g., a "C1-16 alkyl" can have from 1 to 16 carbon atoms). In some aspects, an alkyl group has 1 to 9 carbon atoms ("C1-9 alkyl"). An alkyl group can be saturated or unsaturated, i.e., an alkenyl or alkynyl group as defined herein. Unless specified to the contrary, an “alkyl” group includes both saturated alkyl groups and unsaturated alkyl groups. [0174] An alkyl group may be monovalent or polyvalent, depending on the specific chemical context. By way of example, in the formula: , wherein R1 and R2 are each C2-
Figure imgf000027_0001
will be monovalent, while the R2 alkyl will be divalent to accommodate bonding to both of the phenyl rings. [0175] In some aspects, an alkyl group has 1 to 8 carbon atoms ("C1-8 alkyl"). In some aspects, an alkyl group has 1 to 7 carbon atoms ("C1-7 alkyl"). In some aspects, an alkyl group has 1 to 6 carbon atoms ("C1-6 alkyl"). In some aspects, an alkyl group has 1 to 5 carbon atoms ("C1-5 alkyl"). In some aspects, an alkyl group has 1 to 4 carbon atoms ("C1-4 alkyl"). In some aspects, an alkyl group has 1 to 3 carbon atoms ("C1-3 alkyl"). In some aspects, an alkyl group has 1 to 2 carbon atoms ("C1-2 alkyl"). In some aspects, an alkyl group has 1 carbon atom ("C1 alkyl"). In some aspects, an alkyl group has 2 to 6 carbon atoms ("C2-6 alkyl"). Examples of C1-6 alkyl groups include methyl (C1), ethyl (C2), propyl (C3) (e.g., n- propyl, isopropyl), butyl (C4) (e.g., n-butyl, tert-butyl, sec-butyl, iso-butyl), pentyl (C5) (e.g., n-pentyl, 3-pentanyl, amyl, neopentyl, 3- methyl-2-butanyl, tertiary amyl), and hexyl (C6) (e.g., n-hexyl). Additional examples of alkyl groups include n-heptyl (C7), n-octyl (C8), and the like. Unless otherwise specified, each instance of an alkyl group is independently unsubstituted (an "unsubstituted alkyl") or substituted (a "substituted alkyl") with one or more substituents (e.g., halogen, such as F). In certain aspects, the alkyl group is an unsubstituted C1-10 alkyl (such as unsubstituted C1-6 alkyl, e.g., -CH3 (Me), unsubstituted ethyl (Et), unsubstituted propyl (Pr, e.g., unsubstituted n-propyl (n-Pr), unsubstituted isopropyl (i-Pr)), unsubstituted butyl (Bu, e.g., unsubstituted n-butyl (n-Bu), unsubstituted tert-butyl (tert-Bu or t-Bu), unsubstituted sec-butyl (sec-Bu), unsubstituted isobutyl (i-Bu)). In certain aspects, the alkyl group is a substituted C1-10 alkyl (such as substituted C1-6 alkyl, e.g., -CF3, Bn). [0176] The term "haloalkyl" is a substituted alkyl group, wherein one or more of the hydrogen atoms are independently replaced by a halogen, e.g., fluoro, bromo, chloro, or iodo. In some aspects, the haloalkyl moiety has 1 to 8 carbon atoms ("C1-8 haloalkyl"). In some aspects, the haloalkyl moiety has 1 to 6 carbon atoms ("C1-6 haloalkyl"). In some aspects, the haloalkyl moiety has 1 to 4 carbon atoms ("C1-4 haloalkyl"). In some aspects, the haloalkyl moiety has 1 to 3 carbon atoms ("C1-3 haloalkyl"). In some aspects, the haloalkyl moiety has 1 to 2 carbon atoms ("C1-2 haloalkyl"). Examples of haloalkyl groups include -CHF2, -CH2F, -CF3, -CH2CF3, -CF2CF3, -CF2CF2CF3, -CCl3, -CFCl2, -CF2Cl, and the like. [0177] The term "hydroxyalkyl" is a substituted alkyl group, wherein one or more of the hydrogen atoms are independently replaced by a hydroxyl. In some aspects, the hydroxyalkyl moiety has 1 to 8 carbon atoms ("C1-8 hydroxyalkyl"). In some aspects, the hydroxyalkyl moiety has 1 to 6 carbon atoms ("C1-6 hydroxyalkyl"). In some aspects, the hydroxyalkyl moiety has 1 to 4 carbon atoms ("C1-4 hydroxyalkyl"). In some aspects, the hydroxyalkyl moiety has 1 to 3 carbon atoms ("C1-3 hydroxyalkyl"). In some aspects, the hydroxyalkyl moiety has 1 to 2 carbon atoms ("C1-2 hydroxyalkyl"). [0178] The term "alkoxy" refers to an alkyl group, as defined herein, appended through an oxygen atom. In some aspects, the alkoxy moiety has 1 to 8 carbon atoms ("C1-8 alkoxy"). In some aspects, the alkoxy moiety has 1 to 6 carbon atoms ("C1-6 alkoxy"). In some aspects, the alkoxy moiety has 1 to 4 carbon atoms ("C1-4 alkoxy"). In some aspects, the alkoxy moiety has 1 to 3 carbon atoms ("C1-3 alkoxy"). In some aspects, the alkoxy moiety has 1 to 2 carbon atoms ("C1-2 alkoxy"). Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy and tert-butoxy. [0179] The term "haloalkoxy" refers to a haloalkyl group, as defined herein, appended through an oxygen atom. In some aspects, the alkoxy moiety has 1 to 8 carbon atoms ("C1-8 haloalkoxy"). In some aspects, the alkoxy moiety has 1 to 6 carbon atoms ("C1-6 haloalkoxy"). In some aspects, the alkoxy moiety has 1 to 4 carbon atoms ("C1-4 haloalkoxy"). In some aspects, the alkoxy moiety has 1 to 3 carbon atoms ("C1-3 haloalkoxy"). In some aspects, the alkoxy moiety has 1 to 2 carbon atoms ("C1-2 haloalkoxy"). Representative examples of haloalkoxy include, but are not limited to, difluoromethoxy, trifluoromethoxy, and 2,2,2-trifluoroethoxy. [0180] The term "alkoxyalkyl" is a substituted alkyl group, wherein one or more of the hydrogen atoms are independently replaced by an alkoxy group, as defined herein. In some aspects, the alkoxyalkyl moiety has 1 to 8 carbon atoms ("C1-8 alkoxyalkyl"). In some aspects, the alkoxyalkyl moiety has 1 to 6 carbon atoms ("C1-6 alkoxyalkyl"). In some aspects, the alkoxyalkyl moiety has 1 to 4 carbon atoms ("C1-4 alkoxyalkyl"). In some aspects, the alkoxyalkyl moiety has 1 to 3 carbon atoms ("C1-3 alkoxyalkyl"). In some aspects, the alkoxyalkyl moiety has 1 to 2 carbon atoms ("C1-2 alkoxyalkyl"). By way of example, a C3alkoxyC3alkyl group includes, but is not limited to, the groups having the formula: –CH2CH2CH2OCH2CH2CH3, –CH2CH2CH2OCH(CH3)2, – CH(CH3)CH2OCH(CH3)2, [0181] The term "heteroalkyl" refers to an alkyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (i.e., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. By way of example, a heteroC1-6alkyl (which may also be designated a C1-6heteroalkyl) group includes, but is not limited to, the following structures: .
Figure imgf000029_0001
group bonded through the specified heteroatom. By way of example, a OC1-6heteroalkyl group includes, but it not limited to, the following structures: . g from 1 to 20 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-20 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 18 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-18 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 16 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-16 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 14 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-14 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 12 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-12 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 10 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-10 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 8 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-8 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 6 carbon atoms and 1 or more heteroatoms within the parent chain ("heteroC1-6 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 4 carbon atoms and 1 or 2 heteroatoms within the parent chain ("heteroC1-4 alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 3 carbon atoms and 1 heteroatom within the parent chain ("heteroC1-3alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 to 2 carbon atoms and 1 heteroatom within the parent chain ("heteroC1-2alkyl"). In some aspects, a heteroalkyl group is a saturated group having 1 carbon atom and 1 heteroatom ("heteroC1alkyl"). In some aspects, the heteroalkyl group defined herein is a partially unsaturated group having 1 or more heteroatoms within the parent chain and at least one unsaturated carbon, such as a carbonyl group. For example, a heteroalkyl group may comprise an amide or ester functionality in its parent chain such that one or more carbon atoms are unsaturated carbonyl groups. Unless otherwise specified, each instance of a heteroalkyl group is independently unsubstituted (an "unsubstituted heteroalkyl") or substituted (a "substituted heteroalkyl") with one or more substituents. In certain aspects, the heteroalkyl group is an unsubstituted heteroC1-20alkyl. In certain aspects, the heteroalkyl group is an unsubstituted heteroC1-10alkyl. In certain aspects, the heteroalkyl group is a substituted heteroC1-20alkyl. In certain aspects, the heteroalkyl group is an unsubstituted heteroC1-10alkyl. [0184] The term "alkenyl" refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 10 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, 3, or 4 double bonds). In some aspects, an alkenyl group has 2 to 9 carbon atoms ("C2-9 alkenyl"). In some aspects, an alkenyl group has 2 to 8 carbon atoms ("C2-8 alkenyl"). In some aspects, an alkenyl group has 2 to 7 carbon atoms ("C2-7 alkenyl"). In some aspects, an alkenyl group has 2 to 6 carbon atoms ("C2-6alkenyl"). In some aspects, an alkenyl group has 2 to 5 carbon atoms ("C2-5alkenyl"). In some aspects, an alkenyl group has 2 to 4 carbon atoms ("C2-4alkenyl"). In some aspects, an alkenyl group has 2 to 3 carbon atoms ("C2- 3alkenyl"). In some aspects, an alkenyl group has 2 carbon atoms ("C2 alkenyl"). The one or more carbon-carbon double bonds can be internal (such as in 2- butenyl) or terminal (such as in 1-butenyl). Examples of C2-4 alkenyl groups include ethenyl (C2), 1-propenyl (C3), 2- propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), and the like. Examples of C2-6 alkenyl groups include the aforementioned C2-4 alkenyl groups as well as pentenyl (C5), pentadienyl (C5), hexenyl (C6), and the like. Additional examples of alkenyl include heptenyl (C7), octenyl (C8), octatrienyl (C8), and the like. Unless otherwise specified, each instance of an alkenyl group is independently unsubstituted (an "unsubstituted alkenyl") or substituted (a "substituted alkenyl") with one or more substituents. In certain aspects, the alkenyl group is an unsubstituted C2-10 alkenyl. In certain aspects, the alkenyl group is a substituted C2-10 alkenyl. In an alkenyl group, a C=C double bond for which the stereochemistry is not specified (e.g., -CH=CHCH3 or ) may be an (E)- or (Z)-double bond. [0185] An alkenyl group may
Figure imgf000031_0001
or polyvalent, which the skilled person will recognize is dependent on the specific chemical context. By way of example, in the formula: , rein R1
Figure imgf000031_0002
whe and R2 are each C2- group will be monovalent, while the R2 alkenyl will be divalent, to accommodate bonding to both of the phenyl rings. [0186] The term "heteroalkenyl" refers to an alkenyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (i.e., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain aspects, a heteroalkenyl group refers to a group having from 2 to 10 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain ("heteroC2-10alkenyl"). In some aspects, a heteroalkenyl group has 2 to 9 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain ("heteroC2-9alkenyl"). [0187] In some aspects, a heteroalkenyl group has 2 to 8 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain ("heteroC2-8alkenyl"). In some aspects, a heteroalkenyl group has 2 to 7 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain ("heteroC2-7alkenyl"). In some aspects, a heteroalkenyl group has 2 to 6 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain ("heteroC2-6alkenyl"). In some aspects, a heteroalkenyl group has 2 to 5 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain ("heteroC2-5alkenyl"). In some aspects, a heteroalkenyl group has 2 to 4 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain ("heteroC2-4 alkenyl"). In some aspects, a heteroalkenyl group has 2 to 3 carbon atoms, at least one double bond, and 1 heteroatom within the parent chain ("heteroC2-3alkenyl"). In some aspects, a heteroalkenyl group has 2 to 6 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain ("heteroC2-6alkenyl"). Unless otherwise specified, each instance of a heteroalkenyl group is independently unsubstituted (an "unsubstituted heteroalkenyl") or substituted (a "substituted heteroalkenyl") with one or more substituents. In certain aspects, the heteroalkenyl group is an unsubstituted heteroC2-10alkenyl. In certain aspects, the heteroalkenyl group is a substituted heteroC2-10alkenyl. [0188] The term "alkynyl" refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 10 carbon atoms and one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 triple bonds) ("C2-10alkynyl"). In some aspects, an alkynyl group has 2 to 9 carbon atoms ("C2-9alkynyl"). In some aspects, an alkynyl group has 2 to 8 carbon atoms ("C2- 8alkynyl"). In some aspects, an alkynyl group has 2 to 7 carbon atoms ("C2-7alkynyl"). In some aspects, an alkynyl group has 2 to 6 carbon atoms ("C2-6alkynyl"). In some aspects, an alkynyl group has 2 to 5 carbon atoms ("C2-5alkynyl"). In some aspects, an alkynyl group has 2 to 4 carbon atoms ("C2-4alkynyl"). In some aspects, an alkynyl group has 2 to 3 carbon atoms ("C2-3alkynyl"). In some aspects, an alkynyl group has 2 carbon atoms ("C2 alkynyl"). The one or more carbon-carbon triple bonds can be internal (such as in 2-butynyl) or terminal (such as in 1-butynyl). Examples of C2-4 alkynyl groups include, without limitation, ethynyl (C2), 1-propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), 2-butynyl (C4), and the like. Examples of C2-6 alkenyl groups include the aforementioned C2-4 alkynyl groups as well as pentynyl (C5), hexynyl (C6), and the like. Additional examples of alkynyl include heptynyl (C7), octynyl (C8), and the like. Unless otherwise specified, each instance of an alkynyl group is independently unsubstituted (an "unsubstituted alkynyl") or substituted (a "substituted alkynyl") with one or more substituents. In certain aspects, the alkynyl group is an unsubstituted C2-10 alkynyl. In certain aspects, the alkynyl group is a substituted C2-10 alkynyl. An alkynyl group may be monovalent or polyvalent, as defined above for alkenyl. [0189] The term "heteroalkynyl" refers to an alkynyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (i.e., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain aspects, a heteroalkynyl group refers to a group having from 2 to 10 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain ("heteroC2-10alkynyl"). In some aspects, a heteroalkynyl group has 2 to 9 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain ("heteroC2-9alkynyl"). In some aspects, a heteroalkynyl group has 2 to 8 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain ("heteroC2- 8alkynyl"). In some aspects, a heteroalkynyl group has 2 to 7 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain ("heteroC2-7alkynyl"). In some aspects, a heteroalkynyl group has 2 to 6 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain ("heteroC2-6alkynyl"). In some aspects, a heteroalkynyl group has 2 to 5 carbon atoms, at least one triple bond, and 1 or 2 heteroatoms within the parent chain ("heteroC2-5alkynyl"). In some aspects, a heteroalkynyl group has 2 to 4 carbon atoms, at least one triple bond, and l or 2 heteroatoms within the parent chain ("heteroC2- 4alkynyl"). In some aspects, a heteroalkynyl group has 2 to 3 carbon atoms, at least one triple bond, and 1 heteroatom within the parent chain ("heteroC2-3alkynyl"). In some aspects, a heteroalkynyl group has 2 to 6 carbon atoms, at least one triple bond, and 1 or 2 heteroatoms within the parent chain ("heteroC2-6alkynyl"). Unless otherwise specified, each instance of a heteroalkynyl group is independently unsubstituted (an "unsubstituted heteroalkynyl") or substituted (a "substituted heteroalkynyl") with one or more substituents. In certain aspects, the heteroalkynyl group is an unsubstituted heteroC2-10alkynyl. In certain aspects, the heteroalkynyl group is a substituted heteroC2-10alkynyl. [0190] The term "carbocyclyl," “cycloalkyl,” or "carbocyclic" refers to a radical of a non- aromatic cyclic hydrocarbon group having from 3 to 14 ring carbon atoms ("C3- 14carbocyclyl") and zero heteroatoms in the non-aromatic ring system. In some aspects, a carbocyclyl group has 3 to 10 ring carbon atoms ("C3-10carbocyclyl"). In some aspects, a carbocyclyl group has 3 to 8 ring carbon atoms ("C3-8carbocyclyl"). In some aspects, a carbocyclyl group has 3 to 7 ring carbon atoms ("C3-7carbocyclyl"). In some aspects, a carbocyclyl group has 3 to 6 ring carbon atoms ("C3-6carbocyclyl"). In some aspects, a carbocyclyl group has 4 to 6 ring carbon atoms ("C4-6carbocyclyl"). In some aspects, a carbocyclyl group has 5 to 6 ring carbon atoms ("C5-6carbocyclyl"). In some aspects, a carbocyclyl group has 5 to 10 ring carbon atoms ("C5-10carbocyclyl"). Exemplary C3-6 carbocyclyl groups include, without limitation, cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), and the like. [0191] Exemplary C3-8carbocyclyl groups include, without limitation, the aforementioned C3-6 carbocyclyl groups as well as cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptanyl (C7), bicyclo[2.2.2]octanyl (C8), and the like. Exemplary C3-10 carbocyclyl groups include, without limitation, the aforementioned C3-8 carbocyclyl groups as well as cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C10), cyclodecenyl (C10), octahydro-1H-indenyl (C9), decahydronaphthalenyl (C10), spiro[4.5]decanyl (C10), and the like. As the foregoing examples illustrate, in certain aspects, the carbocyclyl group is either monocyclic ("monocyclic carbocyclyl") or polycyclic (e.g., containing a fused, bridged or spiro ring system such as a bicyclic system ("bicyclic carbocyclyl") or tricyclic system ("tricyclic carbocyclyl")) and can be saturated or can contain one or more carbon-carbon double or triple bonds. "Carbocyclyl" also includes ring systems wherein the carbocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups wherein the point of attachment is on the carbocyclyl ring, and in such instances, the number of carbons continues to designate the number of carbons in the carbocyclic ring system. Unless otherwise specified, each instance of a carbocyclyl group is independently unsubstituted (an "unsubstituted carbocyclyl") or substituted (a "substituted carbocyclyl") with one or more substituents. In certain aspects, the carbocyclyl group is an unsubstituted C3-14 carbocyclyl. In certain aspects, the carbocyclyl group is a substitute C3-14 carbocyclyl. [0192] In some aspects, "carbocyclyl" is a monocyclic, saturated carbocyclyl group having from 3 to 14 ring carbon atoms ("C3-14cycloalkyl"). In some aspects, a cycloalkyl group has 3 to 10 ring carbon atoms ("C3-10cycloalkyl"). In some aspects, a cycloalkyl group has 3 to 8 ring carbon atoms ("C3-8cycloalkyl"). In some aspects, a cycloalkyl group has 3 to 6 ring carbon atoms ("C3-6cycloalkyl"). In some aspects, a cycloalkyl group has 4 to 6 ring carbon atoms ("C4-6cycloalkyl"). In some aspects, a cycloalkyl group has 5 to 6 ring carbon atoms ("C5-6cycloalkyl"). In some aspects, a cycloalkyl group has 5 to 10 ring carbon atoms ("C5- 10cycloalkyl"). Examples of C5-6 cycloalkyl groups include cyclopentyl (C5) and cyclohexyl (C6). Examples of C3-6 cycloalkyl groups include the aforementioned C5-6 cycloalkyl groups as well as cyclopropyl (C3) and cyclobutyl (C4). Examples of C3-8 cycloalkyl groups include the aforementioned C3-6 cycloalkyl groups, as well as cycloheptyl (C7) and cyclooctyl (C8). Unless otherwise specified, each instance of a cycloalkyl group is independently unsubstituted (an "unsubstituted cycloalkyl") or substituted (a "substituted cycloalkyl") with one or more substituents. In certain aspects, the cycloalkyl group is an unsubstituted C3-14 cycloalkyl. In certain aspects, the cycloalkyl group is a substituted C3-14 cycloalkyl. [0193] As used herein, the term “heterocyclyl” refers to an aromatic (also referred to as a heteroaryl), unsaturated, or saturated cyclic hydrocarbon that includes at least one heteroatom in the cycle. For example, the term "heterocyclyl" or "heterocyclic" refers to a radical of a 3- to 14-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("3-14 membered heterocyclyl"). In heterocyclyl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. A heterocyclyl group can either be monocyclic ("monocyclic heterocyclyl") or polycyclic (e.g., a fused, bridged or spiro ring system such as a bicyclic system ("bicyclic heterocyclyl") or tricyclic system ("tricyclic heterocyclyl")), and can be saturated or can contain one or more carbon-carbon double or triple bonds. Heterocyclyl polycyclic ring systems can include one or more heteroatoms in one or both rings. "Heterocyclyl" also includes ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more carbocyclyl groups wherein the point of attachment is either on the carbocyclyl or heterocyclyl ring, or ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclyl ring, and in such instances, the number of ring members continues to designate the number of ring members in the heterocyclyl ring system. Unless otherwise specified, each instance of heterocyclyl is independently unsubstituted (an "unsubstituted heterocyclyl") or substituted (a "substituted heterocyclyl") with one or more substituents. In certain aspects, the heterocyclyl group is an unsubstituted 3-14 membered heterocyclyl. In certain aspects, the heterocyclyl group is a substituted 3-14 membered heterocyclyl. [0194] In some aspects, a heterocyclyl group is a 5-10 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-10 membered heterocyclyl"). In some aspects, a heterocyclyl group is a 5-8 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-8 membered heterocyclyl"). In some aspects, a heterocyclyl group is a 5-6 membered non-aromatic ring system having ring carbon atoms and 1- 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-6 membered heterocyclyl"). In some aspects, the 5-6 membered heterocyclyl has 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some aspects, the 5-6 membered heterocyclyl has 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some aspects, the 5-6 membered heterocyclyl has a 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. [0195] Exemplary 3-membered heterocyclyl groups containing 1 heteroatom include, without limitation, aziridinyl, oxiranyl, and thiiranyl. Exemplary 4-membered heterocyclyl groups containing 1 heteroatom include, without limitation, azetidinyl, oxetanyl, and thietanyl. Exemplary 5-membered heterocyclyl groups containing 1 heteroatom include, without limitation, tetrahydrofuranyl, dihydrofurany1, tetrahydrothiopheny1, dihydrothiopheny1, pyrrolidiny1, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary 5- membered heterocyclyl groups containing 2 heteroatoms include, without limitation, dioxolanyl, oxathiolanyl and dithiolanyl. Exemplary 5-membered heterocyclyl groups containing 3 heteroatoms include, without limitation, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclyl groups containing 1 heteroatom include, without limitation, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclyl groups containing 2 heteroatoms include, without limitation, piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6-membered heterocyclyl groups containing 3 heteroatoms include, without limitation, triazinyl. Exemplary 7- membered heterocyclyl groups containing 1 heteroatom include, without limitation, azepanyl, oxepanyl and thiepanyl. Exemplary 8-membered heterocyclyl groups containing 1 heteroatom include, without limitation, azocanyl, oxecanyl and thiocanyl. Exemplary bicyclic heterocyclyl groups include, without limitation, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, tetrahydrobenzothienyl, tetrahydrobenzofuranyl, tetrahydroindolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydrochromenyl, octahydroisochromenyl, decahydronaphthyridinyl, decahydro-1,8- naphthyridinyl, octahydropyrrolo[3,2-b]pyrrole, indolinyl, phthalimidyl, naphthalimidyl, chromanyl, chromenyl, lH-benzo[e][1,4]diazepinyl, 1,4,5,7-tetrahydropyrano[3,4-b]pyrrolyl, 5,6-dihydro-4H-furo[3,2-b]pyrrolyl, 6,7-dihydro-5H furo[3,2-b]pyranyl, 5,7-dihydro-4H- thieno[2,3-c]pyranyl, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, 2,3-dihydrofuro[2,3- b]pyridinyl, 4,5,6,7 -tetrahydro-1H-pyrrolo[2,3-b ]pyridinyl, 4,5,6,7-tetrahydrofuro[3,2- c]pyridinyl, 4,5,6,7-tetrahydrothieno[3,2-b]pyridinyl, 1,2,3,4- tetrahydro-1,6-naphthyridinyl, and the like. [0196] The term "aryl" refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 π electrons shared in a cyclic array) having 6-14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system ("C6-14aryl"). In some aspects, an aryl group has 6 ring carbon atoms ("C6aryl"; e.g., phenyl). In some aspects, an aryl group has 10 ring carbon atoms ("C10aryl"; e.g., naphthyl such as 1-naphthyl and 2-naphthyl). In some aspects, an aryl group has 14 ring carbon atoms ("C14aryl"; e.g., anthracyl). "Aryl" also includes ring systems wherein the aryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the radical or point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system. Unless otherwise specified, each instance of an aryl group is independently unsubstituted (an "unsubstituted aryl") or substituted (a "substituted aryl") with one or more substituents. In certain aspects, the aryl group is an unsubstituted C6-14aryl. In certain aspects, the aryl group is a substituted C6-14 aryl. [0197] The term "heteroaryl" refers to a radical of a 5-14 membered monocyclic or polycyclic (e.g., bicyclic, tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 π electrons shared in a cyclic array) having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-14 membered heteroaryl"). In heteroaryl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. Heteroaryl polycyclic ring systems can include one or more heteroatoms in one or both rings. "Heteroaryl" includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heteroaryl ring system. "Heteroaryl" also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused polycyclic (aryl/heteroaryl) ring system. Polycyclic heteroaryl groups wherein one ring does not contain a heteroatom (e.g., indolyl, quinolinyl, carbazolyl, and the like), the point of attachment can be on either ring, i.e., either the ring bearing a heteroatom (e.g., 2-indolyl) or the ring that does not contain a heteroatom (e.g., 5-indolyl). [0198] In some aspects, a heteroaryl group is a 5-10 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-10 membered heteroaryl"). In some aspects, a heteroaryl group is a 5-8 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-8 membered heteroaryl"). In some aspects, a heteroaryl group is a 5-6 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-6 membered heteroaryl"). In some aspects, the 5-6 membered heteroaryl has 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some aspects, the 5-6 membered heteroaryl has 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some aspects, the 5-6 membered heteroaryl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Unless otherwise specified, each instance of a heteroaryl group is independently unsubstituted (an "unsubstituted heteroaryl") or substituted (a "substituted heteroaryl") with one or more substituents. In certain aspects, the heteroaryl group is an unsubstituted 5-14 membered heteroaryl. In certain aspects, the heteroaryl group is a substituted 5-14 membered heteroaryl. [0199] Exemplary 5-membered heteroaryl groups containing 1 heteroatom include, without limitation, pyrrolyl, furanyl, and thiophenyl. Exemplary 5-membered heteroaryl groups containing 2 heteroatoms include, without limitation, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing 3 heteroatoms include, without limitation, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing 4 heteroatoms include, without limitation, tetrazolyl. Exemplary 6- membered heteroaryl groups containing 1 heteroatom include, without limitation, pyridinyl. Exemplary 6-membered heteroaryl groups containing 2 heteroatoms include, without limitation, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing 3 or 4 heteroatoms include, without limitation, triazinyl and tetrazinyl, respectively. Exemplary 7- membered heteroaryl groups containing 1 heteroatom include, without limitation, azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6- bicyclic heteroaryl groups include, without limitation, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6- bicyclic heteroaryl groups include, without limitation, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. Exemplary tricyclic heteroaryl groups include, without limitation, phenanthridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenothiazinyl, phenoxazinyl, and phenazinyl. [0200] In general, the inclusion of the prefix “alk” in front of a substituent name indicates there is an alkyl group (as defined herein) connecting the named substitutent with the rest of the compound. For example, "alkaryl" (which is a subset of alkyl) refers to an alkyl group substituted by an aryl group, wherein the point of attachment is on the alkyl moiety, and "alkheteroaryl" (which is a subset of "alkyl") refers to an alkyl group substituted by a heteroaryl group, wherein the point of attachment is on the alkyl moiety. The number of carbons atoms may be specified in the alkyl chain, the named substituent, or both. For example, C1-2alkC6aryl refers to a phenyl ring (which may be substituted) connected via a 1-2 carbon alkylene group. [0201] Affixing the suffix "-ene" to a group indicates the group is a polyvalent moiety, e.g., boned to two or more groups. Alkylene is the polyvalent moiety of alkyl, alkenylene is the divalent moiety of alkenyl, alkynylene is the divalent moiety of alkynyl, heteroalkylene is the divalent moiety of heteroalkyl, heteroalkenylene is the divalent moiety of heteroalkenyl, heteroalkynylene is the divalent moiety of heteroalkynyl, carbocyclylene is the divalent moiety of carbocyclyl, heterocyclylene is the divalent moiety of heterocyclyl, arylene is the divalent moiety of aryl, and heteroarylene is the divalent moiety of heteroaryl. [0202] A group is optionally substituted unless expressly provided otherwise. The term "optionally substituted" refers to being substituted or unsubstituted. In certain aspects, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted. "Optionally substituted" refers to a group which may be substituted or unsubstituted (e.g., "substituted" or "unsubstituted" alkyl, "substituted" or "unsubstituted" alkenyl, "substituted" or "unsubstituted" alkynyl, "substituted" or "unsubstituted" heteroalkyl, "substituted" or "unsubstituted" heteroalkenyl, "substituted" or "unsubstituted" heteroalkynyl, "substituted" or "unsubstituted" carbocyclyl, "substituted" or "unsubstituted" heterocyclyl, "substituted" or "unsubstituted" aryl or "substituted" or "unsubstituted" heteroaryl group). In general, the term "substituted" means that at least one hydrogen present on a group is replaced with a permissible substituent, e.g., a substituent which, upon substitution, results in a stable compound, e.g., a compound that does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction. Unless otherwise indicated, a "substituted" group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position. The term "substituted" is contemplated to include substitution with all permissible substituents of organic compounds and includes any of the substituents described herein that results in the formation of a stable compound. The present disclosure contemplates any and all such combinations in order to arrive at a stable compound. For purposes of this disclosure, heteroatoms such as nitrogen may have hydrogen substituents and/or any suitable substituent as described herein, which satisfy the valencies of the heteroatoms and result in the formation of a stable moiety. The disclosure is not intended to be limited in any manner by the exemplary substituents described herein. [0203] Exemplary carbon atom substituents include, but are not limited to, halogen, -CN, - NO2, -N3, -SO2H, -SO3H, -OH, -ORaa, -ON(Rbb)2, -N(Rbb)2, -N(Rbb)3 +X-, -N(ORcc)Rbb, -SH, - SRaa, -SSRcc, -C(=O)Raa, -CO2H, -CHO, -C(ORcc)3, -CO2Raa, -OC(=O)Raa, -OCO2Raa, - 2, 2,
Figure imgf000040_0001
SC(=O)Raa, -P(=O)(Raa)2, -P(=O)(ORcc)2, -OP(=O)(Raa)2, -OP(=O)(ORcc)2, - P(=O)(N(Rbb)2)2,-OP(=O)(N(Rbb)2)2, -NRbbP(=O)(Raa)2, -NRbbP(=O)(ORcc)2, - NRbbP(=O)(N(Rbb)2)2, -P(Rcc)2, -P(ORcc)2, -P(Rcc)3 +X–, -P(ORcc)3 +X–, -P(Rcc)4, -P(ORcc)2, -
Figure imgf000041_0001
, 10alkyl, heteroC2-10 alkenyl, heteroC2-10alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rdd groups; wherein X– is a counterion; or two geminal hydrogens on a carbon atom are replaced with the group =O, =S, =NN(Rbb)2, =NNRbbC(=O)Raa, =NNRbbC(=O)ORaa, =NNRbbS(=O)2Raa, =NRbb or =NORcc; each instance of Raa is, independently, selected from C1-10alkyl, C1-10perhaloalkyl, C2- 10alkenyl, C2-10 alkynyl, heteroC1-10alkyl, heteroC2-10 alkenyl, heteroC2-10alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14aryl, and 5-14 membered heteroaryl, or two Raa groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rdd groups; each instance of Rbb is, independently, selected from hydrogen, -OH, -ORaa, -N(Rcc)2, -CN, -C(=O)Raa, -C(=O)N(Rcc)2, -CO2Raa, -SO2Raa, -C(=NRcc)ORaa, - C(=NRcc)N(Rcc)2, -SO2N(Rcc)2, -SO2Rcc, -SO2ORcc, -SORaa, -C(=S)N(Rcc)2, -C(=O)SRcc, - C(=S)SRcc, -P(=O)(Raa)2, -P(=O)(ORcc)2, -P(=O)(N(Rcc)2)2, C1-10 alkyl, C1-10perhaloalkyl, C2- 10alkenyl, C2-10alkynyl, heteroC1-10alkyl, heteroC2-10alkenyl, heteroC2-10alkynyl, C3- 10carbocyclyl, 3-14 membered heterocyclyl, C6-14aryl, and 5-14 membered heteroaryl, or two Rbb groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rdd groups; wherein X– is a counterion; each instance of Rcc is, independently, selected from hydrogen, C1-10alkyl, C1-10perhaloalkyl, C2-10alkenyl, C2-10alkynyl, heteroC1-10 alkyl, heteroC2-10alkenyl, heteroC2-10alkynyl, C3-10carbocyclyl, 3-14 membered heterocyclyl, C6- 14aryl, and 5-14 membered heteroaryl, or two Rcc groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rdd groups; each instance of Rdd is, independently, selected from halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -ORee, - ON(Rff)2, -N(Rff)2, -N(Rff)3 +X–, -N(ORee)Rff, -SH, -SRee, -SSRee, -C(=O)Ree, -CO2H, - CO2Ree, -OC(=O)Ree, -OCO2Ree, -C(=O)N(Rff)2, -OC(=O)N(Rff)2, -NRffC(=O)Ree, - NRffCO2Ree, -NRffC(=O)N(Rff)2, -C(=NRff)ORee, -OC(=NRff)Ree, -OC(=NRff)ORee, - C(=NRff)N(Rff)2, -OC(=NRff)N(Rff)2, -NRffC(=NRff)N(Rff)2, -NRffSO2Ree, -SO2N(Rff)2, - SO2Ree, -SO2ORee, -OSO2Ree, -S(=O)Ree, -Si(Ree)3, -OSi(Ree)3, -C(=S)N(Rff)2, -C(=O)SRee, - C(=S)SRee, -SC(=S)SRee, -P(=O)(ORee)2, -P(=O)(Ree)2, -OP(=O)(Ree)2, -OP(=O)(ORee)2, C1-6 alkyl, C1-6 perhaloalkyl, C2-6 alkenyl, C2-6 alkynyl, heteroC1-6 alkyl, heteroC2-6 alkenyl, heteroC2-6 alkynyl, C3-10 carbocyclyl, 3-10 membered heterocyclyl, C6-10 aryl, 5-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rgg groups, or two geminal Rdd substituents can be joined to form =O or =S; wherein X– is a counterion; each instance of Ree is, independently, selected from C1- 6alkyl, C1-6perhaloalkyl, C2-6alkenyl, C2-6alkynyl, heteroC1-6 alkyl, heteroC2-6alkenyl, heteroC2-6alkynyl, C3-10carbocyclyl, C6-10aryl, 3-10 membered heterocyclyl, and 3-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rgg groups; each instance of Rff is, independently, selected from hydrogen, C1-6 alkyl, C1-6 perhaloalkyl, C2-6 alkenyl, C2-6 alkynyl, heteroC1-6 alkyl, heteroC2-6 alkenyl, heteroC2-6 alkynyl, C3-10 carbocyclyl, 3-10 membered heterocyclyl, C6-10 aryl and 5- 10 membered heteroaryl, or two Rff groups are joined to form a 3-10 membered heterocyclyl or 5-10 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rgg groups; and each instance of Rgg is, independently, halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OC1-6 alkyl, -ON(C1-6 alkyl)2, -N(Cl-6 alkyl)2, -N(Cl-6 alkyl)3+X–, -NH(Cl-6 alkyl)2+ X–, -NH2(C1-6 alkyl)+X–, -NH3+X–, -N(OC1-6 alkyl)(Cl-6 alkyl), -N(OH)(Cl-6 alkyl), -NH(OH), -SH, -SC1-6 alkyl, -SS(Cl-6 alkyl), -C(=O)(Cl-6 alkyl), - CO2H, -CO2(C1-6 alkyl), -OC(=O)(Cl-6 alkyl), -OCO2(C1-6 alkyl), -C(=O)NH2, -C(=O)N(C1-6 alkyl)2, -OC(=O)NH(C1-6 alkyl), -NHC(=O)(Cl-6 alkyl), -N(Cl-6 alkyl)C(=O)( C1-6 alkyl), - NHCO2(C1-6 alkyl), -NHC(=O)N(Cl-6 alkyl)2, -NHC(=O)NH(Cl-6 alkyl), -NHC(=O)NH2, - C(=NH)O(Cl-6 alkyl), -OC(=NH)(Cl-6 alkyl), -OC(=NH)OCl-6 alkyl, -C(=NH)N(Cl-6 alkyl)2, - C(=NH)NH(Cl-6 alkyl), -C(=NH)NH2, -OC(=NH)N(C1-6 alkyl)2, -OC(=NH)NH(C1-6 alkyl), - OC(=NH)NH2, -NHC(=NH)N(C1-6 alkyl)2, -NHC(=NH)NH2, -NHSO2(C1-6 alkyl), -SO2N(C1- 6 alkyl)2, -SO2NH(C1-6 alkyl), -SO2NH2, -SO2(C1-6 alkyl), -SO2O(C1-6 alkyl), -OSO2(C1-6 alkyl), -SO(C1-6 alkyl), -Si(Cl-6 alkyl)3, -OSi(Cl-6 alkyl)3, -C(=S)N(Cl-6 alkyl)2, -C(=S)NH(Cl- 6 alkyl), -C(=S)NH2, -C(=O)S(Cl-6 alkyl), -C(=S)SC1-6 alkyl, -SC(=S)SC1-6 alkyl, - P(=O)(OC1-6 alkyl)2, -P(=O)(C1-6 alkyl)2, -OP(=O)(Cl-6 alkyl)2, -OP(=O)(OCl-6 alkyl)2, C1- 6alkyl, C1-6perhaloalkyl, C2-6alkenyl, C2-6alkynyl, heteroC1-6alkyl, heteroC2-6alkenyl, heteroC2-6alkynyl, C3-10carbocyclyl, C6-10aryl, 3-10 membered heterocyclyl, 5-10 membered heteroaryl; or two geminal Rgg substituents can be joined to form =O or =S; wherein X– is a counterion. [0204] The term "halo" or "halogen" refers to fluorine (fluoro, -F), chlorine (chloro, -Cl), bromine (bromo, -Br), or iodine (iodo, -I). [0205] The term "hydroxyl" or "hydroxy" refers to the group -OH. The term "substituted hydroxyl" or "substituted hydroxyl," by extension, refers to a hydroxyl group wherein the oxygen atom directly attached to the parent molecule is substituted with a group other than hydrogen, and includes groups selected from -ORaa, -ON(Rbb)2, -OC(=O)SRaa, -OC(=O)Raa, - OCO2Raa, -OC(=O)N(Rbb)2, -OC(=NRbb)Raa, -OC(=NRbb)ORaa, -OC(=NRbb)N(Rbb)2, - OS(=O)Raa, -OSO2Raa, -OSi(Raa)3, -OP(Rcc)2, -OP(Rcc)3+X–, -OP(ORcc)2, -OP(ORcc)3+X–, - 2, wherein X–, Raa, Rbb and Rcc are as
Figure imgf000043_0001
[0206] The term "amino" refers to the group -NH2. The term "substituted amino," by extension, refers to a monosubstituted amino, a disubstituted amino, or a trisubstituted amino. In certain aspects, the "substituted amino" is a monosubstituted amino or a disubstituted ammino group. [0207] The term "monosubstituted amino" refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with one hydrogen and one group other than hydrogen, and includes groups selected from -NH(Rbb), -NHC(=O)Raa, - NHCO2Raa, -NHC(=O)N(Rbb)2, -NHC(=NRbb)N(Rbb)2, -NHSO2Raa, -NHP(=O)(ORcc)2, and -NHP(=O)(N(Rbb)2)2, wherein Raa, Rbb, and Rcc are as defined herein, and wherein Rbb of the group -NH(Rbb) is not hydrogen. [0208] The term "disubstituted amino" refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with two groups other than hydrogen, and includes groups selected from -N(Rbb)2, -NRbbC(=O)Raa, -NRbbCO2Raa, - NRbbC(=O)N(Rbb)2, -NRbbC(=NRbb)N(Rbb)2, -NRbbSO2Raa, -NRbbP(=O)(ORcc)2, and - NRbbP(=O)(N(Rbb)2)2, wherein Raa, Rbb, and Rcc are as defined herein, with the proviso that the nitrogen atom directly attached to the parent molecule is not substituted with hydrogen. [0209] The term "trisubstituted amino" refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with three groups, and includes groups selected from -N(Rbb)2 and -N(Rbb)3+X–, wherein Rbb and X– are as defined herein. [0210] The term "sulfonyl" refers to a group selected from -SO2N(Rbb)2, -SO2Raa, and SO2ORaa, wherein Raa and Rbb are as defined herein. [0211] The term "sulfinyl" refers to the group -S(=O)Raa, wherein Raa is as defined herein. [0212] The term "acyl" refers to a group having the general formula -C(=O)RX1, - C(=O)ORX1, -C(=O)-O-C(=O)RX1, -C(=O)SRX1, -C(=O)N(RX1)2, -C(=S)RX1, -C(=S)N(RX1)2, -C(=S)O(RX1), -C(=S)S(RX1), -C(=NRX1)RX1, -C(=NRX1)ORX1, -C(=NRX1)SRX1, and - C(=NRX1)N(RX1)2, wherein RX1 is hydrogen; halogen; substituted or unsubstituted hydroxyl; substituted or unsubstituted thiol; substituted or unsubstituted amino; substituted or unsubstituted acyl, cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkyl; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkenyl; substituted or unsubstituted alkynyl; substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, mono- or di- aliphaticamino, mono- or di- heteroaliphaticamino, mono- or dialkylamino, mono- or di-heteroalkylamino, mono- or di-arylamino, or mono- or diheteroarylamino; or two RX1 groups taken together form a 5- to 6-membered heterocyclic ring. [0213] Exemplary acyl groups include aldehydes (-CHO), carboxylic acids (-CO2H), ketones, acyl halides, esters, amides, imines, carbonates, carbamates, and ureas. Acyl substituents include but are not limited to, any of the substituents described herein that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted). [0214] The term "carbonyl" refers a group wherein the carbon directly attached to the parent molecule is sp2 hybridized, and is substituted with an oxygen, nitrogen or sulfur atom, e.g., a group selected from ketones (e.g., -C(=O)Raa), carboxylic acids (e.g., -CO2H), aldehydes( CHO), esters (e.g., -CO2Raa, -C(=O)SRaa, -C(=S)SRaa), amides (e.g., -C(=O)N(Rbb)2, C(=O)NRbbSO2Raa, -C(=S)N(Rbb)2, and imines (e.g., -C(=NRbb)Raa, -C(=NRbb)ORaa), C(=NRbb)N(Rbb)2, wherein Raa and Rbb are as defined herein. [0215] The term "oxo" refers to the group =O, and the term "thiooxo" refers to the group =S. [0216] The term “cyano” refers to the group –CN. [0217] The term “azide” and “azido” refers to the group –N3. [0218] Nitrogen atoms can be substituted or unsubstituted as valency permits, and include primary, secondary, tertiary, and quaternary nitrogen atoms. Exemplary nitrogen atom substituents include, but are not limited to, hydrogen, -OH, -ORaa, -N(Rcc)2, -CN, -C(=O)Raa, -C(=O)N(Rcc)2, -CO2Raa, -SO2Raa, -C(=NRbb)Raa, -C(=NRcc)ORaa, -C(=NRcc)N(Rcc)2, - SO2N(Rcc)2, -SO2Rcc, -SO2ORcc, -SORaa, -C(=S)N(Rcc)2, -C(=O)SRcc, -C(=S)SRcc, - P(=O)(ORcc)2, -P(=O)(Raa)2, -P(=O)(N(Rcc)2)2, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, heteroC1-10 alkyl, heteroC2-10 alkenyl, heteroC2-10 alkynyl, C3-10 carbocyclyl, 3- 14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two Rcc groups attached to an N atom are joined to form a 3-14 membered heterocyclyl or a 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rdd groups, and wherein Raa, Rbb, Rcc, and Rdd are as defined herein. [0219] As used herein, the designation of a polyvalent moiety without specifying the specific order of attachment is intended to cover all possible arrangements. By way of example, a compound is represented by the formula: A-X-B, [0220] wherein X is NHC(=O) embraces both: .
Figure imgf000045_0001
[0221] As used herein, a chemical bond depicted: represents either a single, double, or triple bond, valency permitting. By way of example, d [0222] An ele pulls electron density towards itself, away from other portions of the molecule, e.g., through resonance and/or inductive effects. Exemplary electron-withdrawing groups include F, Cl, Br, I, NO2, CN, SO2R, SO3R, SO2NR2, C(O)R1a; C(O)OR, and C(O)NR2 (wherein R is H or an alkyl, aryl, heteroaryl, cycloalkyl, heterocyclyl group) as well as alkyl group substituted with one or more of those group [0223] An electron-donating group is a functional group or atom that pushes electron density away from itself, towards other portions of the molecule, e.g., through resonance and/or inductive effects. Exemplary electron-donating groups include unsubstituted alkyl or aryl groups, OR and N(R)2 and alkyl groups substituted with one or more OR and N(R)2 groups. [0224] Unless stated to the contrary, a formula with chemical bonds shown only as solid lines and not as wedges or dashed lines contemplates each possible isomer, e.g., each enantiomer, diastereomer, and meso compound, and a mixture of isomers, such as a racemic or scalemic mixture. Unless stated to the contrary, a formula depicting one or more stereochemical features does not exclude the presence of other isomers. [0225] Some compounds disclosed herein may exist as one or more tautomers. Tautomers are interconvertible structural isomers that differ in the position of one or more protons or other labile atom. By way of example: .
Figure imgf000046_0001
The prevalence of one tautomeric form over another will depend on the specific chemical compound as well as its local chemical environment. Unless specified to the contrary, the depiction of one tautomeric form is inclusive of all possible tautomeric forms. [0226] Unless stated to the contrary, a substituent drawn without explicitly specifying the point of attachment indicates that the substituent may be attached at any possible atom. For example, in a benzofuran depicted as: , the substituent may be present at any one of the six possible carbon atoms.
Figure imgf000047_0001
herein, the term “null,” when referring to a possible identity of a chemical moiety, indicates that the group is absent, and the two adjacent groups are directly bonded to one another. By way of example, for a genus of compounds having the formula CH3-X-CH3, if X is null, then the resulting compound has the formula CH3-CH3. [0228] As used herein, the term “(meth)acrylic acid” refers to a genus of compounds, including both acrylic acid and methacrylic acid. The same convention is used with reference to (meth)acrylates, (meth)acrylamides, and polymers containing the same. [0229] Compounds disclosed herein may be provided in the form of salts. In some implementations, the compounds may be provided in the form of biocompatible salts. As used herein, biocompatible salts are those which can be combined with biofluids and tissues (for example, blood) without significantly adversely affecting any of the components of said biofluids and tissues. Biocompatible salts also include those which do not include any toxic or otherwise harmful ionic species. The skilled person understands that when biofluids, like blood, come into contact with salts there can be an ionic exchange, leading to the introduction of ionic species into a subject. Accordingly, for implementations in which the composite membranes are used in a clinical setting, the composite membranes will not include any species that can exchange to the point of being toxic or harmful to the patient. [0230] In some implementations, the compounds may be provided as acid addition salts formed with inorganic acids, for example, hydrochloric, hydrobromic, sulfuric, phosphoric, and nitric acids and the like; salts formed with organic acids such as acetic, oxalic, tartaric, succinic, maleic, fumaric, gluconic, citric, malic, methanesulfonic, p-toluenesulfonic, napthalenesulfonic, and polygalacturonic acids, and the like; salts formed from elemental anions such as chloride, bromide, and iodide; salts formed from metal hydroxides, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, and magnesium hydroxide; salts formed from metal carbonates, for example, sodium carbonate, potassium carbonate, calcium carbonate, and magnesium carbonate; salts formed from metal bicarbonates, for example, sodium bicarbonate and potassium bicarbonate; salts formed from metal sulfates, for example, sodium sulfate and potassium sulfate; and salts formed from metal nitrates, for example, sodium nitrate and potassium nitrate. The skilled person understands that depending on the local chemical environment, an ionizable group may exist in neutral or ionic form, or both. The depiction of one ionic form is inclusive of all other forms. [0231] As used herein, the designation of a polymeric or oligomeric system having the formula: — [Unit A]x—[Unit B]y— indicates that the polymer or oligomer is composed of the depicted units in the ratio specified by the x and y subscript, but in the absence of an indication to the contrary, it does not imply any particular order or arrangement of the units. By way of example, the formula: — [Unit A]2—[Unit B]3— includes, but is not limited to: [Unit B]—[Unit A]—[Unit B]—[Unit A]—[Unit B]; [Unit B]—[Unit B]—[Unit B]—[Unit A]—[Unit A]; and [Unit B]—[Unit B]—[Unit A]—[Unit A]—[Unit B]. The subscript units typically refer to the relative ratio of the individual monomer units used to prepare the polymeric or oligomeric system, assuming 100% conversion of the monomer unit that is the limiting reagent. The relative ratio can be expressed as a weight ratio, mole ratio, or volume ratio. POLYMERS [0232] It is known in the polymer chemistry that a polyurethane molecular structure comprised of polyols (usually macrodiols) forming the soft segment, where the hard segment is composed of diisocyanates, chain extenders (microdiols) and the urethane linkages. When used in vivo for medical device applications, the degradation of the polyurethanes is primarily caused by the bond breakage in the polyol groups, the soft segments of the macromolecule. The disclosure is directed to the compositional combinations involving poly(isobutylene) (PIB) based polyurethanes that would overcome the susceptibility of the soft segments by chemistry modification that will further improve the biostability of PIB polyurethanes. In the following aspects described are approaches to achieve this goal by introducing a small extent of double bonds into the structure of PIB polyurethane to create sites for cross-linking. Without wishing to be bound by any theory, it was assumed that a mild crosslinking among the different portions of the polyurethane can enhance the in vivo stability because of the presence of additional covalent bonds that can resist oxidative, enzymatic and hydrolytic degradation. [0233] Disclosed herein are biostable crosslinked polyurethanes prepared by crosslinking a polyurethane having the formula: wherein
Figure imgf000049_0001
a is from 1-10,000; b is from 1-10,000; c is from 0-500; Rcap is a capping group; [soft] represents a macrodiol segment including a poly(isobutylene) component; [DI] represents a diisocyante component; [CE] represents a chain extender component; [CC] represents a chain connector component, wherein one or more of [soft], [DI], [CE], and [CC] include one or more crosslinkable groups. [0234] In still further aspects, the biostable crosslinked polyurethanes disclosed herein are prepared from polyurethanes that can have a molecular weight from 50,000 g/mol to 1,000,000 g/mol, including exemplary values of 75,000 g/mol, 100,000 g/mol, 150,000 g/mol, 200,000 g/mol, 300,000 g/mol, 400,000 g/mol, 500,000 g/mol, 600,000 g/mol, 700,000 g/mol, 800,000 g/mol, 900,000 g/mol, and 950,000 g/mol. In yet still further aspects, the molecular weight of the polyurethane that is used to prepare the biostable crosslinked polyurethanes is from 100,000 g/mol to 300,000 g/mol, including exemplary values of 110,000 g/mol, 120,000 g/mol, 130,000 g/mol, 140,000 g/mol, 150,000 g/mol, 160,000 g/mol, 170,000 g/mol, 180,000 g/mol, 190,000 g/mol, 200,000 g/mol, 210,000 g/mol, 220,000 g/mol, 230,000 g/mol, 240,000 g/mol, 250,000 g/mol, 260,000 g/mol, 270,000 g/mol, 280,000 g/mol, 290,000 g/mol, and 295,000 g/mol. [0235] Without wishing to be bound by any theory, it is hypothesized that the molecular weight needs to be balanced to allow enhanced the tensile strength and hence biostability of the polyurethane while maintaining the elasticity and softness of the polyurethane. [0236] As used herein, a crosslinkable group is a functional group capable of undergoing a reaction to form a covalent bond. Exemplary crosslinkable groups include carbon-carbon double bonds, carbon-carbon triple bonds, epoxides, carboxylic acids and activated carboxylic acids, Michael acceptors (i.e., α,β unsaturated carbonyls and sulfones), a clickable group (i.e., a functional group capable of undergoing a click ligation reaction, e.g., 2,3 dipolar cycloaddition, an inverse electron demand Diels-Alder cycloaddition, a thiol-ene reaction). It will be appreciated that some of the above crosslinkable groups can directly crosslink with another of the same functional group, i.e., carbon-carbon double bonds and carbon-carbon triple bonds, while other functional groups must be paired in order to form a covalent bond (suitable pairs include alkyne:azide, epoxide:amine, epoxide:alcohol, epoxide:carboxylic acid, sulfide:olefin; Michael acceptor:amine, Michael acceptor:sulfide, etc. The second functional group is also part of the polyurethane or may be provided as part of a separate crosslinking agent. By way of example, a polyurethane having terminal-alkyne functional groups may be crosslinked by copper catalyzed click reaction with a bis-azido compound. In some implementations, an olefin-containing polyurethane may be crosslinked in the absence of an additional crosslinker, while in other implementations, an olefin-containing polyurethane may be crosslinked in the presence of a crosslinker, for example, a divinyl compound (2,2-bis[4-(2-hydroxy-3-methacryloxy-propoxy)phenyl]propane, tetraethylene glycol diacrylate, 1,9-nonanediol dimethacrylate, divinylbenzene). The designation of a polyurethane crosslinked by an additional crosslinking agent does not exclude the possibility that some portion of the polyurethane may be self-crosslinked, depending upon the chemistry. [0237] When the polyurethane is crosslinked by a separate crosslinking agent (or multiple crosslinking agents), the crosslinking agent may be provided in a given weight ratio relative to the polyurethane. In some implementations, the crosslinking agent is present in an amount that is 0.01-50 wt.%, including exemplary values of 0.05 wt %, 0.1 wt %, 0.5 wt %, 0.7 wt %, 1.0 wt %, 2.5 wt %, 3 wt %, 3.5 wt %, 4 wt %, 4.5 wt %, 5 wt %, 5.5 wt %, 6 wt %, 6.5 wt %, 7 wt %, 7.5 wt %, 8 wt %, 8.5 wt %, 9 wt %, 9.5 wt %, 10 wt %, 12.5 wt %, 15 wt %, 17.5 wt %, 20 wt %, 25 wt %, 30 wt %, 35 wt %, 40 wt %, 45 wt %, and 49 wt % of the polyurethane. Unless specified to the contrary, the given wt.% percent refers to the total mass of the combined crosslinking agents. In some implementations, the crosslinking agent is present in an amount that is 0.01-10 wt.%, 0.01-5 wt.%, 0.01-2.5 wt.%, 0.01-1 wt.%, 0.01-0.5 wt.%, 0.1-5 wt.%, 0.1-2.5 wt.%, 0.1-1 wt.%, 0.1-0.5 wt.%, 0.5-5 wt.%, 0.5-2.5 wt.%, 0.5-1 wt.%, 1-5 wt.%, 1-2.5 wt.%, 2.5-5 wt.%, 3.5-10 wt.%, 5-10 wt.%, 5-15 wt.%, 10-20 wt.%, or 15-25 wt.%, relative to the total mass of the polyurethane. [0238] In some implementations, the crosslinking agent is present in an amount that is from 0.01 wt % to 10 wt %, including exemplary values of 0.01 wt.%, 0.05 wt.%, 0.1 wt.%, 0.25 wt.%, 0.5 wt.%, 0.75 wt.%, 1 wt.%, 2 wt.%, 2.5 wt.%, 3 wt.%, 4 wt.%, 5 wt.%, 7.5 wt.%, and 9.5 wt.%, relative to the total mass of the polyurethane. [0239] The [soft] and [CE] components may be present in a variety of different ratios. In some implementations, the [soft] component is present in an amount from 1-99 wt.%, including exemplary values of 2.5 wt %, 5 wt %, 7.5 wt %, 10 wt %, 15 wt %, 20 wt %, 25 wt %, 30 wt %, 35 wt %, 40 wt %, 45 wt %, 50 wt %, 55 wt %, 60 wt %, 65 wt %, 70 wt %, 75 wt %, 80 wt %, 85 wt %, 90 wt %, and 95 wt % relative to the [CE] component. With respect to the ratio of [soft] and [CE], the wt% refers to the relative weight of macrodiol and chain extender compounds used to prepare the polyurethane. [0240] In some implementations the [soft] unit is present in an amount from 1-25 wt.%, including exemplary values of 1 wt %, 2 wt %, 3 wt %, 4 wt %, 5 wt %, 6 wt %, 7 wt %, 8 wt %, 9 wt %, 10 wt %, 11 wt %, 12 wt %, 13 wt %, 14 wt %, 15 wt %, 16 wt %, 17 wt %, 18 wt %, 19 wt %, 20 wt %, 21 wt %, 22 wt %, 23 wt %, and 24 wt %; from 25-50 wt.%, including exemplary values of 26 wt %, 27 wt %, 28 wt %, 29 wt %, 30 wt %, 31 wt %, 32 wt %, 33 wt %, 34 wt %, 35 wt %, 36 wt %, 37 wt %, 38 wt %, 39 wt %, 40 wt %, 41 wt %, 42 wt %, 43 wt %, 44 wt %, 45 wt %, 46 wt %, 47 wt %, 48 wt %, and 49 wt %; from 50-75 wt.%, including exemplary values of 51 wt %, 52 wt %, 53 wt %, 54 wt %, 55 wt %, 56 wt %, 57 wt %, 58 wt %, 59 wt %, 60 wt %, 61 wt %, 62 wt %, 63 wt %, 64 wt %, 65 wt %, 66 wt %, 67 wt %, 68 wt %, 69 wt %, 70 wt %, 71 wt %, 72 wt %, 73 wt %, and 74 wt %; from 75-99 wt.%, including exemplary values of 76 wt %, 77 wt %, 78 wt %, 79 wt %, 80 wt %, 81 wt %, 82 wt %, 83 wt %, 84 wt %, 85 wt %, 86 wt %, 87 wt %, 88 wt %, 89 wt %, 90 wt %, 91 wt %, 92 wt %, 93 wt %, 94 wt %, 95 wt %, 96 wt %, 97 wt %, 98 wt %, and 99 wt %; or from 25-75 wt.%, including exemplary values of 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, 55 wt%, 60 wt%, 65 wt%, and 70 wt% relative to the [CE] component. [0241] In some implementations, the [soft] unit is present in an amount of 90-99.9 wt.%, including exemplary values of 91 wt%, 91.5 wt%, 92 wt%, 92.5 wt%, 93 wt%, 93.5 wt%, 94 wt%, 94.5 wt%, 95 wt%, 95.5 wt%, 96 wt%, 96.5 wt%, 97 wt%, 97.5 wt%, 98 wt%, 98.5 wt%, 99 wt%, and 99.5 wt% relative to the [CE] portion. In some implementations, the [soft] unit is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97- 99 wt.%, or from 99-99.99 wt.%, relative to the [CE] component. [0242] In some implementations, the [soft] unit is present in an amount of 90% by weight relative to the [CE] component. In some implementations, the [soft] unit is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the [CE] component. [0243] In some implementations, the [soft] unit is present in an amount of at least 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2.5 wt.%, 1 wt.%, or at least 0.5 wt.%, relative to the [CE] component. In yet other implementations, the [soft] unit is present in an amount of 0.5 wt.% to 80 wt.%, including exemplary values of 1 wt%, 2.5 wt%, 5 wt%, 10 wt%, 20 wt%, 30 wt%, 40 wt%, 50 wt%, 60 wt%, and 70 wt%. [0244] The polyurethane may be self-crosslinked (i.e., a functional group in one polyurethane forms a covalent bond with a functional group in a second polyurethane), or the polyurethane may be crosslinked in the presence of the crosslinking agent, i.e., a compound having two or more functional groups, wherein one functional group forms a covalent bond with one polyurethane, and another functional group on the same molecule forms a covalent bond with a second polyurethane. Soft component [0245] The [soft] component can be provided as a macrodiol having a given average molecular weight. In some implementations, the macrodiol has a molecular weight from 100-100,000 Da, from 100-50,000 Da, from 100-25,000 Da, from 100-10,000 Da, from 100- 5,000 Da, from 100-2,500 Da, from 100-1,000 Da, from 100-500 Da, from 250-1,000 Da, from 500-1,000 Da, from 500-1,500 Da, from 1,000-2,000 Da, from 1,000-3,000 Da, from 1,000-5,000 Da, from 1,500-2,500 Da, from 1,500-3,000 Da, from 2,500-5,000 Da, from 2,500-10,000 Da, from 5,000-10,000 Da, from 10,000-25,000 Da, from 10,000-50,000 Da, from 25,000-50,000 Da, from 25,000-75,000 Da, or from 50,000-100,000 Da. It is understood that the macrodiol can have a molecular weight that has any value between any two mentioned above ranges. [0246] In some implementations, the [soft] unit includes a poly(alkenyl) component. In some implementations, the poly(alkenyl) is a poly(1,3-butadiene), poly(2,3-dimethyl-1,3- butadiene), or poly(isoprene), preferably poly(isoprene), e.g., a poly(isobutylene-co- isoprene). In certain implementations, the poly(isobutylene-co-isoprene) component is a random copolymer. In certain implementations, the poly(isobutylene-co-isoprene) component is a block copolymer. [0247] In some implementations, the [soft] unit includes a poly(isobutylene-co-isoprene) component, wherein the isobutylene portion is present in an amount of 0.1-99 wt.%, including exemplary values of 0.5 wt %, 5 wt %, 7.5 wt %, 10 wt %, 15 wt %, 20 wt %, 25 wt %, 30 wt %, 35 wt %, 40 wt %, 45 wt %, 50 wt %, 55 wt %, 60 wt %, 65 wt %, 70 wt %, 75 wt %, 80 wt %, 85 wt %, 90 wt %, and 95 wt % relative to the isoprene portion. In yet still further aspects, the isobutylene portion is present in any values between any foregoing values or within a range formed by any of the foregoing values. For example, the isobutylene portion is present in an amount 0.5 wt % to 95 wt %, or 1 wt% to 90 wt%, or 5 wt % to 85 wt %, or 1 wt % to 85 wt % or 10 wt % to 70 wt %, or 1 wt % to 70 wt%, or 1 wt % to 60 wt % or 1 wt % to 50 wt %, and so one. In some implementations the isobutylene portion is present in an amount from 1-25 wt.%, including exemplary values of 1 wt %, 2 wt %, 3 wt %, 4 wt %, 5 wt %, 6 wt %, 7 wt %, 8 wt %, 9 wt %, 10 wt %, 11 wt %, 12 wt %, 13 wt %, 14 wt %, 15 wt %, 16 wt %, 17 wt %, 18 wt %, 19 wt %, 20 wt %, 21 wt %, 22 wt %, 23 wt %, and 24 wt %; from 25-50 wt.%, including exemplary values of 26 wt %, 27 wt %, 28 wt %, 29 wt %, 30 wt %, 31 wt %, 32 wt %, 33 wt %, 34 wt %, 35 wt %, 36 wt %, 37 wt %, 38 wt %, 39 wt %, 40 wt %, 41 wt %, 42 wt %, 43 wt %, 44 wt %, 45 wt %, 46 wt %, 47 wt %, 48 wt %, and 49 wt %; from 50-75 wt.%, including exemplary values of 51 wt %, 52 wt %, 53 wt %, 54 wt %, 55 wt %, 56 wt %, 57 wt %, 58 wt %, 59 wt %, 60 wt %, 61 wt %, 62 wt %, 63 wt %, 64 wt %, 65 wt %, 66 wt %, 67 wt %, 68 wt %, 69 wt %, 70 wt %, 71 wt %, 72 wt %, 73 wt %, and 74 wt %; from 75-99 wt.%, including exemplary values of 76 wt %, 77 wt %, 78 wt %, 79 wt %, 80 wt %, 81 wt %, 82 wt %, 83 wt %, 84 wt %, 85 wt %, 86 wt %, 87 wt %, 88 wt %, 89 wt %, 90 wt %, 91 wt %, 92 wt %, 93 wt %, 94 wt %, 95 wt %, 96 wt %, 97 wt %, 98 wt %, and 99 wt %; or from 25-75 wt.%, including exemplary values of 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, 55 wt%, 60 wt%, 65 wt%, and 70 wt% relative to the isoprene. [0248] In some implementations, the [soft] unit includes a poly(isobutylene-co-isoprene) component, wherein the isobutylene portion is present in an amount of 90-99.9 wt.%, including exemplary values of 91 wt%, 91.5 wt%, 92 wt%, 92.5 wt%, 93 wt%, 93.5 wt%, 94 wt%, 94.5 wt%, 95 wt%, 95.5 wt%, 96 wt%, 96.5 wt%, 97 wt%, 97.5 wt%, 98 wt%, 98.5 wt%, 99 wt%, and 99.5 wt% relative to the isoprene portion. In some implementations, the isobutylene portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the isoprene. [0249] In some implementations, the isobutylene portion is present in an amount of 90% by weight relative to the isoprene portion. In some implementations, the isobutylene portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the isoprene. [0250] In some implementations, the isobutylene portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2.5 wt.%, 1 wt.%, or 0.5 wt.%, relative to the isoprene portion. In yet other implementations, the isobutylene portion is present in an amount of 0.5 wt.% to 80 wt.%, including exemplary values of 1 wt%, 2.5 wt%, 5 wt%, 10 wt%, 20 wt%, 30 wt%, 40 wt%, 50 wt%, 60 wt%, and 70 wt% relative to the isoprene portion. [0251] In some implementations, the [soft] unit includes a poly(alkylene) component. In some implementations, the poly(alkylene) is a polyethylene, polypropylene, poly(ethylene- co-propylene) polymer. In certain implementations, the poly(alkylene) is block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In certain implementations, the poly(alkylene) is a random copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In such aspects, it is hypothesized that the presence of poly(alkylene) can affect the crystallinity of the polymer, for example, making the polymer more crystalline and, as a result, more fatigue-resistant. In still further aspects, it is assumed that the presence of poly(alkylene) components can minimize the phase separation of the hard segments of the polymer. [0252] In some implementations the poly(alkylene) portion is present in an amount of 1-99 wt.%, including exemplary values of 2.5 wt %, 5 wt %, 7.5 wt %, 10 wt %, 15 wt %, 20 wt %, 25 wt %, 30 wt %, 35 wt %, 40 wt %, 45 wt %, 50 wt %, 55 wt %, 60 wt %, 65 wt %, 70 wt %, 75 wt %, 80 wt %, 85 wt %, 90 wt %, and 95 wt % relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0253] In some implementations the poly(alkylene) portion is present in an amount from 1- 25 wt% including exemplary values of 1 wt %, 2 wt %, 3 wt %, 4 wt %, 5 wt %, 6 wt %, 7 wt %, 8 wt %, 9 wt %, 10 wt %, 11 wt %, 12 wt %, 13 wt %, 14 wt %, 15 wt %, 16 wt %, 17 wt %, 18 wt %, 19 wt %, 20 wt %, 21 wt %, 22 wt %, 23 wt %, and 24 wt %; from 25-50 wt.%, including exemplary values of 26 wt %, 27 wt %, 28 wt %, 29 wt %, 30 wt %, 31 wt %, 32 wt %, 33 wt %, 34 wt %, 35 wt %, 36 wt %, 37 wt %, 38 wt %, 39 wt %, 40 wt %, 41 wt %, 42 wt %, 43 wt %, 44 wt %, 45 wt %, 46 wt %, 47 wt %, 48 wt %, and 49 wt %; from 50-75 wt.%, including exemplary values of 51 wt %, 52 wt %, 53 wt %, 54 wt %, 55 wt %, 56 wt %, 57 wt %, 58 wt %, 59 wt %, 60 wt %, 61 wt %, 62 wt %, 63 wt %, 64 wt %, 65 wt %, 66 wt %, 67 wt %, 68 wt %, 69 wt %, 70 wt %, 71 wt %, 72 wt %, 73 wt %, and 74 wt %; from 75-99 wt.%, including exemplary values of 76 wt %, 77 wt %, 78 wt %, 79 wt %, 80 wt %, 81 wt %, 82 wt %, 83 wt %, 84 wt %, 85 wt %, 86 wt %, 87 wt %, 88 wt %, 89 wt %, 90 wt %, 91 wt %, 92 wt %, 93 wt %, 94 wt %, 95 wt %, 96 wt %, 97 wt %, 98 wt %, and 99 wt %; or from 25-75 wt.%, including exemplary values of 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, 55 wt%, 60 wt%, 65 wt%, and 70 wt% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0254] In some implementations the poly(alkylene) portion is present in an amount from 90- 95 wt.%, including exemplary values of 90.5 wt.%, 91 wt.%, 91.5 wt.%, 92 wt.%, 92.5 wt.%, 93 wt.%, 93.5 wt.%, 94 wt.%, and 94.5 wt.%; from 95-99 wt.%, including exemplary values of 95.5 wt.%, 96 wt.%, 96.5 wt.%, 97 wt.%, 97.5 wt.%, 98 wt.%, 98.5 wt.%,; from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0255] In some implementations the poly(alkylene) portion is present in an amount from 1- 10 wt.%, including exemplary values of 2 wt.%, 3 wt.%, 4 wt.%, 5 wt.%, 6 wt.%, 7 wt.%, 8 wt.%, and 9 wt.%; from 5-15 wt.%, including exemplary values of 6 wt.%, 7 wt.%, 8 wt.%, 9 wt.%, 10 wt.%, 11 wt.%, 12 wt.%, 13 wt.%, and 1 wt.%; from 10-25 wt.%, including exemplary values of 11 wt.%, 12 wt.%, 13 wt.%, 14 wt.%, 15 wt.%, 16 wt.%, 17 wt.%, 18 wt.%, 19 wt.%, 20 wt.%, 21 wt.%, 22 wt.%, 23 wt.%, and 24 wt.%; from 1-5 wt.%, including exemplary values of 1.5 wt.%, 2 wt.%, 2.5 wt.%, 3 wt.%, 3.5 wt.%, 4 wt.%, and 4.5 wt.%; or from 1-2 wt.%, including exemplary values of 1.1 wt.%, 1.2 wt.%, 1.3 wt.%, 1.4 wt.%, 1.5 wt.%, 1.6 wt.%, 1.7 wt.%, 1.8 wt.%, and 1.9 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0256] In some implementations, the poly(alkylene) portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0257] In some implementations, the poly(alkylene) portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0258] In some implementations, the poly(alkylene) portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the poly(alkylene) portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0259] In some implementations, the [soft] unit includes a poly(meth)acrylate portion. In some implementations, the poly(meth)acrylate is derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec- butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof. In certain implementations, the poly(meth)acrylate is a block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component. In certain implementations, the poly(meth)acrylate is a random copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component. [0260] In some implementations, the poly(meth)acrylate portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the poly(meth)acrylate portion is present in an amount from 1-25 wt.%, from 25-50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood, and as disclosed above, the poly(meth)acrylate portion can be present in any amount that falls between any of the two mentioned above ranges. [0261] In some implementations, the poly(meth)acrylate portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood, and as disclosed above, the poly(meth)acrylate portion can be present in any amount that falls between any of the two mentioned above ranges. [0262] In some implementations, the poly(meth)acrylate portion is present in an amount from 1-10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood, and as disclosed above, the poly(meth)acrylate portion can be present in any amount that falls between any of the two mentioned above ranges. [0263] In some implementations, the poly(meth)acrylate portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0264] In some implementations, the poly(meth)acrylate portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co- isoprene) portion. It is also understood that the poly(meth)acrylate portion can be present in any amount in any range between any of the disclosed amounts. [0265] In some implementations, the poly(meth)acrylate portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the poly(meth)acrylate portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%,10 wt.%, 5 wt.%, 2 wt.%,1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is also understood that the poly(meth)acrylate portion can be present in any amount in any range between any of the disclosed amounts. [0266] In some implementations, the [soft] unit includes a poly(siloxane) component in addition to the polyisobutylene segment. In some implementations, the poly(siloxane) is a poly(dimethylsiloxane), a poly(vinyl-methylsiloxane), or a poly(divinylsiloxane. In certain implementations, the poly(siloxane) is a block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component. Without wishing to be bound by any theory, it was hypothesized that polysiloxane components can increase the softness, flexibility and elasticity of the polymer. [0267] In some implementations, the poly(siloxane) portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations the poly(siloxane) portion is present in an amount from 1-25 wt.%, from 25- 50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. Similarly to the above, it is understood that the poly(siloxane) portion can be present in an amount that falls between any two values disclosed above. [0268] In some implementations, the poly(siloxane) portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be present in an amount that falls between any two values disclosed above. [0269] In some implementations, the poly(siloxane) portion is present in an amount from 1- 10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be present in an amount that falls between any two values disclosed above. [0270] In some implementations, the poly(siloxane) portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0271] In some implementations, the poly(siloxane) portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is also understood that the poly(siloxane) portion can be present in an amount in any range between any of the disclosed amounts. [0272] In some implementations, the poly(siloxane) portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the poly(siloxane) portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%,10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is also understood that the poly(siloxane) portion can be present in an amount in any range between any of the disclosed amounts. [0273] In some implementations, the [soft] unit includes a polyethylene glycol component in addition to the polyisobutylene segment. In some implementations, the polyethylene glycol has a molecular weight (in Daltons) from 100-100,000, from 500-10,000, from 1,000-50,000, from 500-2,500, from 2,500-7,500, from 5,000-10,000, from 10,000-25,000, from 25,000- 50,000, or from 50,000-100,000. It is further understood that the polyethylene glycol can have a molecular weight value that falls between any two mentioned above values. [0274] In some implementations, the polyethylene glycol portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the polyethylene glycol portion is present in an amount from 1-25 wt.%, from 25-50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be present in an amount that falls between any two values disclosed above. [0275] In some implementations, the polyethylene glycol portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be present in an amount that falls between any two values disclosed above. [0276] In some implementations, the polyethylene glycol portion is present in an amount from 1-10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be present in an amount that falls between any two values disclosed above. [0277] In some implementations, the polyethylene glycol portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0278] In some implementations, the polyethylene glycol portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co- isoprene) portion. It is also understood that the polyethylene glycol portion can be present in an amount in any range between any of the disclosed amounts. [0279] In some implementations, the polyethylene glycol portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the polyethylene glycol portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%,10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is also understood that the polyethylene glycol portion can be present in an amount in any range between any of the disclosed amounts. [0280] In certain aspects, the [soft] segment can have the formula: -[-(A1)d-(A2)e-(A3)f-(A4)g-(A5)h-(A6)peg]-, wherein A1 is (isobutylene), and d is 1-10,000; A2 is C4-20alkenyl, and e is 0-500; A3 is C4-20alkynyl, and f is 0-500; A4 is C2-20alkyl, and g is 0-10,000; A5 is a siloxane, and h is 0-10,000; A6 is a polyethylene glycol, and peg is 0-10,000 wherein d, e, f, g, h, and peg represent the number of monomer units. [0281] In some implementations, d is from 1-10,000, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 200, 500, 1,000, 5,000, and 9,000. It is understood that these values are only exemplary, and any values of d in the disclosed range or any range between any disclosed values can be used. In still further aspects, e is from 0 to 500, including exemplary values 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 200, 300, and 400. It is understood that these values are only exemplary, and any values of e in the disclosed range or any range between any disclosed values can be used. In still further aspects, f is from 0 to 500, including exemplary values 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 200, 300, and 400. It is understood that these values are only exemplary, and any value in the disclosed range or any range between any disclosed values can be used. In some implementations, g is from 1-10,000, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 50,100, 200, 500, 1,000, 5,000, and 9,000. It is understood that these values are only exemplary, and any value of g in the disclosed range or any range between any disclosed values can be used. In some implementations, h is from 1-10,000, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 200, 500, 1,000, 5,000, and 9,000. It is understood that these values are only exemplary, and any values of h in the disclosed range or any range between any disclosed values can be used. In some implementations, peg is from 1-10,000, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 200, 500, 1,000, 5,000, and 9,000. It is understood that these values are only exemplary and any value of peg in the disclosed range or any range between any disclosed values can be used. [0282] In some implementations, the [soft] segment can have the formula: -[-(A1)d’-(A2)e’-(A3)f’-(A4)g’-(A5)h’-(A6)peg’]-, wherein A1, A2, A3, A4, A5, and A6 are as defined above, and d’ is 1-100; e’ is 0-99; f’ is 0-99; g’ is 0-99; h’ is 0-99; and peg’ is 0-99, wherein d’ + e’ + f’ + g’ + h’ + peg’ = 100; and d’, e’, f’, g’, h’, and peg’ represent the wt.% of each component in the soft segment. [0283] In certain implementations, d’ is present in an amount of 1-100 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, and 99.5 wt.%. It is understood that these values are only exemplary and any values of d’ in the disclosed range or any range between any disclosed values can be used. In still further implementations e’ is present in an amount of 1-99 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, 98.5, and 98.5 wt.%. It is understood that these values are only exemplary and any values of e’ in the disclosed range or any range between any disclosed values can be used. In still further implementations f’ is present in an amount of 1-99 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, 98.5, and 98.5 wt.%. It is understood that these values are only exemplary and any values of f’ in the disclosed range or any range between any disclosed values can be used. In still further implementations g’ is present in an amount of 1-99 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, 98.5, and 98.5 wt.%. It is understood that these values are only exemplary and any values of g’ in the disclosed range or any range between any disclosed values can be used. In still further implementations h’ is present in an amount of 1-99 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, 98.5, and 98.5 wt.%. It is understood that these values are only exemplary and any values of h’ in the disclosed range or any range between any disclosed values can be used. In still further implementations peg’ is present in an amount of 1-99 wt %, including exemplary values of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, 98.5, and 98.5 wt.%. It is understood that these values are only exemplary and any values of peg’ in the disclosed range or any range between any disclosed values can be used. [0284] In some implementations, A4 is a mixture of (ethylene) and (propylene), while in other aspects, A4 is (ethylene). [0285] In some implementations, A2 is (1,3-butadiene), (2,3-dimethyl-1,3-butadiene), (isoprene), or a combination thereof. In some implementations, A2 is (isoprene). [0286] In some implementations, A5 is (dimethylsiloxane). [0287] In some implementations, A3 and A6 are absent, i.e., f, f’, peg, and peg’ are all 0. Diisocyanate component [0288] In some implementations, [DI] can include a segment of Formula (1): [Formula (1)], wherein the wavy lines
Figure imgf000062_0001
to any of [soft], [CE], or [CC], wherein R1 is a saturated C2-30 group. Exemplary R1 groups include: ,
Figure imgf000062_0002
, or [Formula (2)], wherein the wavy lines
Figure imgf000063_0001
to any of [soft], [CE], or [CC], wherein R2 is an unsaturated C2-30 group. Exemplary R2 groups include: , . [0290] In
Figure imgf000063_0002
[Formula (3)],
Figure imgf000063_0003
wherein the wavy lines to any of [soft], [CE], or [CC], wherein R3 is a C6-30 aromatic group. As used in the context R3, the C6-30 aromatic group refers to a divalent fragment in which each carbon atom in the shortest sequence of atoms from one nitrogen to the next is part of an aromatic system. Such systems may include sp3 hybridized carbons, so long as such carbons are not part of the shortest path from one nitrogen to the next. Exemplary R3 groups include: . Ch [0291] In some implementations, [CE] includes segments of Formula (4): [Formula (4)], wherein the wavy lines
Figure imgf000064_0001
to [DI], X1 is O or NH; X2 is O or NH; R4 is a saturated C2-30 group. [0292] In some implementations, R4 has the structure: *-(CH2)4aX4a(CH2)4b-#, wherein * represents the point of attachment to X1 and # represents the point of attachment to X2; X4a is null, CHR4a, C(R4a)2,O, NH, or NCH3; R4a is independently C1-8alkyl; 4a is 0-12; and 4b is 0-12, wherein when X4a is null, O, NH, or NCH3 the sum of 4a and 4b is at least 2, and when X4a is CHR4a or C(R4a)2, the sum of 4a and 4b is at least 1. [0293] In some implementations, X1 is O or NH, X2 is NH, X4a is O, 4a is 2-12, and 4b is 0. [0294] In certain implementations, 4a is 2-12, X4a is null, and 4b is 0. [0295] In certain implementations, one of 4a and 4b is 1, and the other of 4a and 4b is 0, and X4a is CHR4a or C(R4a)2. [0296] In some implementations, X4a is C(CH3)2. [0297] In some implementations [CE] includes segments of Formula (5): [Formula (5)], wherein the wavy lines
Figure imgf000065_0001
to [DI], X3 is O or NH; X4 is O or NH; R5 is an unsaturated C2-30 group. [0298] In some aspects, R5 has the structure: *-(CH2)5aX5a(CH2)5b-#, wherein * represents the point of attachment to X3 and # represents the point of attachment to X4; X5a is CHR5a, C(R5a)2, -CH=CH-, or -C≡C-, R5a is, in each case, independently a C2-12 group, wherein when two of R5a are present, at least one of R5a is an unsaturated C2-12 group; 5a is 0-12; and 5b is 0-12, wherein when X5a is CH=CH-, or -C≡C-, then 5a is 1-12, and 5b is 1-12, and when X5a is CHR5a, the sum of 5a and 5b is at least 1. [0299] In some implementations, 5a is 1-12, including 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11; 5b is 1-12, including 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11; and X5a is -CH=CH-. [0300] In some implementations, one of 5a and 5b is 1, and the other of 5a and 5b is 0, and X5a is CHR5a or C(R5a)2. [0301] In some implementations, R5a is C2-4alkenyl, for example, allyl or vinyl. [0302] In some implementations, [DI] only includes segments of Formula (4) and does not include any segments of Formula (5). In some implementations, [DI] only includes segments of Formula (5) and does not include any segments of Formula (4). In some implementations, [DI] can include a mixture of Formula (4) and Formula (5). [DI] can include the segment of Formula (4) in an amount from 1-99% relative to the segment of Formula (5). In the context of Formulas (4) and (5), the ratio refers to the mole ratio of the diisocyanate monomers used to prepare the polyurethane. [0303] In some implementations, [DI] can include the segment of Formula (4) in an amount from 1-25%, from 10-25%, from 25-50%, from 50-75%, from 75-99%, or from 90-99%, relative to the segment of Formula (5). In some implementations, [DI] can include the segment of Formula (4) in an amount that is 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 85% relative to the segment of Formula (5). [0304] In some implementations, [DI] can include the segment of Formula (4) in an amount from 90-99.99%, from 90-95%, from 95-99%, from 95-97%, from 97-99%, or from 98-99%, relative to the segment of Formula (5). In some implementations, [DI] can include the segment of Formula (4) in an amount that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% relative to the segment of Formula (5). [0305] In some implementations, when [DI] includes segments of Formula (5), the [soft] segment will not include a poly(alkenyl) component. In other implementations, when [DI] includes segments of Formula (5), the [soft] segment does include a poly(alkenyl) component, e.g., poly(isoprene). [0306] In some implementations, [CE] includes segments of Formula (6): [Formula (6)], wherein the wavy lines represent points of attachment to [DI], X6 is O or NH; X7 is O or NH; R6 is a C2-30 aromatic group. As used in the context R6, the C6-30 aromatic group refers to a divalent fragment in which each carbon atom in the shortest sequence of atoms from X6 to X7 is part of an aromatic system. Such systems may include sp3 hybridized carbons, so long as such carbons are not part of the shortest path from X6 to X7. Chain connector [0307] In some implementations, [CC] is a segment of Formula (7): [Formula (7)], wherein the wavy lines
Figure imgf000067_0001
to [DI], X8 is O or NH; X9 is O or NH; R7 is an unsaturated C2-30 group. [0308] In certain implementations, X8 and X9 are both O, and R7 is an unsaturated C4-10 group having a single unsaturated carbon-carbon bond. Exemplary R7 groups include: or
Figure imgf000067_0002
point of attachment to X9. [0309] In certain aspects, the polyurethane does not include any [CC]. For implementations where [CC] is present, [CC] may be present in an amount that is from 1-99% relative to [DI]. In this context, the ratio refers to the mole ratio of the diisocyanate monomers and chain extender monomers used to prepare the polyurethane. When more than one diisocyanate monomer is used, the ratio refers to the sum total of all moles of all diisocyanate compounds. [0310] In some implementations, [DI] can be present in an amount that is from 1-25%, from 10-25%, from 25-50%, from 50-75%, from 75-99%, or from 90-99%, relative to [CC]. In some implementations, [DI] can be present in an amount that is 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 85% relative to [CC]. [0311] In some implementations, [DI] can be present in an amount from 90-99.99%, from 90-95%, from 95-99%, from 95-97%, from 97-99%, or from 98-99%, relative to [CC]. In some implementations, [DI] can be present in an amount that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% relative to [CC]. Capping group [0312] In some implementations, the capping group (Rcap) may simply be an unreacted end of component fragments, e.g., OH, COOH, or NH2 (an unreacted isocyanate is hydrolyzed to a primary amine in the presence of water). In other implementations, a capping reagent may be added to terminate the polyurethane polymerization process and install a capping group on the polyurethane. In some instances, the capping group can be a C1-12 alkyl, C6-12 aryl, or C1- 12 alkyl substituted one or more times by C6-12 aryl. The capping group can be resistant to a chemical reaction. Without wishing to be bound by theory, the resistance to chemical reactions can improve oxidative stability, resistance to hydrolysis, and resistance to enzymatic degradation. In certain implementations, the capping group is a C1-12 haloalkyl, C6-12 haloaryl, or C1-12 haloalkyl substituted one or more times by C6-12 haloaryl. Fluorine is a preferred halogen substituent. In some instances, the capping group can be a perfluoroalkyl group or perfluoroaryl, for example, CF3, CF2CF3, C6F5, and the like, while in some instances, the capping group can be a partially fluorinated alkyl group or partially fluorinated aryl group, for example, CH2CF3, C6F3H2, and the like. [0313] The crosslinked polyurethanes described herein may be prepared by the steps: preparing a first mixture comprising a macrodiol (as defined herein) and disocyanate to give a first polyurethane, optionally capping the first polyurethane to give a first capped polyurethane, optionally forming a second reaction mixture comprising a chain extender and the first polyurethane to give a second polyurethane, optionally capping the second polyurethane to give a second capped polyurethane; and crosslinking the first polyurethane, first capped polyurethane, second polyurethane or second capped polyurethane. [0314] In some implementations, the crosslinking may be conducted in the presence of an additional crosslinking agent, and in other implementations, the crosslinking may be conducted in the absence of any separate crosslinking agent. [0315] In some implementations, the polyurethane may be subjected to two or more crosslinking reactions. For example, the polyurethane may first be crosslinked in the absence of a separate crosslinking agent, and then subsequently crosslinked in the presence of an additional crosslinking agent. [0316] In some implementations, the polyurethane may first be crosslinked in the presence of a separate crosslinking agent, and then subsequently crosslinked in the absence of an additional crosslinking agent. In further implementations, the polyurethane may first be crosslinked in the presence of a first additional crosslinking agent, and then subsequently crosslinked in the presence of a second additional crosslinking agent. [0317] In some implementations, the polyurethane may first be crosslinked in the absence of a separate crosslinking agent using a first set of crosslinking conditions, and then subsequently crosslinked in the absence of a separate crosslinking agent, using a second set of crosslinking conditions, wherein the second set of conditions is different from the first. [0318] Crosslinking may be performed by exposing the crosslinkable polyurethane to radiation such as electron beam or ultraviolet (UV) radiation, or heat. The crosslinkable composition may be exposed to heated air or gas, wherein the heated air or gas has a temperature from 25 to 200 °C., from 50-200 °C., from 100 to 200 °C., from 150-200 °C from 25 to 100 °C., from 50-100 °C, or from 100 to 150 °C. It is understood that any values between any two foregoing values can be included. [0319] The heating can be conducted for a period from 0.1–120 minutes, from 1–120 minutes, from 5–120 minutes, from 10–120 minutes, from 30–120 minutes, from 60–120 minutes, from 0.1–60 minutes, from 30–60 minutes, from 1–30 minutes, from 1–10 minutes, from 10–30, or from 20-30 minutes. It is understood that any values between any two foregoing values can be included. [0320] When the polyurethane is crosslinked using an electron beam, an accelerating voltage of 75-350 kV can be used, and a dosage of 5 to 250 kilogray (kGy) can be utilized. When UV is used, a light source of 200 nm to 450 nm is suitable. The power rating of the lamp needed depends on the composition and can be any emitting irradiation at a dosage of at least 0.001 mJ/cm2. In some implementations, the dosage is from 0.01 to 2000 mJ/cm2, from 0.1 to 1000 mJ/cm2, from 1 to 1000 mJ/cm2, or from 10 to 500 mJ/cm2. It is understood that any values between any two foregoing values can be included. [0321] In some implementations, the crosslinking agent can be a C4-30 unsaturated group having at least two carbon-carbon double bonds. In some implementations, the crosslinking agent is a C6-18 unsaturated group, or a C6-12 unsaturated group. Such crosslinking agents may be used when the polyurethane includes one or more carbon-carbon double bonds or carbon- carbon triple bonds. Exemplary agents include diallylmethyl amine, divinylbenze, and ethylene glycol diacrylate. [0322] In some implementations, the crosslinking agent can be a C2-30 group having at least two azide groups. In some implementations, the crosslinking agent is a C2-12 group having at least two azide groups. Such crosslinking agents may be used when the polyurethane includes one or more terminal alkynes. Exemplary agents include polyoxyethylene bis(azide), diethylene glycol bis(azidoacetate), 1,6 diazidohexane, and 4, 4’-bis(azidomethyl)-1,1’- biphenyl. [0323] In some implementations, the crosslinking agent can be a C2-30 group having at least two amine or thiol groups. In some implementations, the crosslinking agent is a C2-12 group having at least two amine or thiol groups. Such crosslinking agents may be used when the polyurethane includes one or more epoxides or Michael acceptors (e.g., α,β unsaturated carbonyl or sulfone). [0324] In certain implementations, the crosslinking agent can be ethylene glycol diacrylate, poly(ethylene glycol) diacrylate, neopentyl glycol diacrylate, trimethylolpropane triacrylate, pentaerythritol triacrylate, glycerol propoxylate triacrylate, trimethylolpropane propoxylate triacrylate, trimethylolpropane ethoxylate triacrylate, pentaerythritol tetraacrylate, di(trimethylolpropane) tetraacrylate, divinylbenzene, divinyl sulfone, 1,4-butanediol divinyl ether, ethylene glycol divinyl ether, di- tri-, and poly-ethylene glycol divinyl ether. [0325] The macrodiol can have an average molecular weight from 100-100,000 Da, from 100-50,000 Da, from 100-25,000 Da, from 100-10,000 Da, from 100-5,000 Da, from 100- 2,500 Da, from 100-1,000 Da, from 100-500 Da, from 250-1,000 Da, from 500-1,000 Da, from 500-1,500 Da, from 1,000-2,000 Da, from 1,000-3,000 Da, from 1,000-5,000 Da, from 1,500-2,500 Da, from 1,500-3,000 Da, from 2,500-5,000 Da, from 2,500-10,000 Da, from 5,000-10,000 Da, from 10,000-25,000 Da, from 10,000-50,000 Da, from 25,000-50,000 Da, from 25,000-75,000 Da, or from 50,000-100,000 Da. Again, as discussed in detail above, it is understood that the macrodiol can have a molecular weight value that falls between any two disclosed above values. [0326] In some implementations, the macrodiol includes a poly(alkenyl) component. In some implementations, the poly(alkenyl) is a poly(1,3-butadiene), poly(2,3-dimethyl-1,3- butadine), or poly(isoprene), preferably poly(isoprene), e.g., a poly(isobutylene-co-isoprene). In certain implementations, the poly(isobutylene-co-isoprene) component is a random copolymer. In certain implementations, the poly(isobutylene-co-isoprene) component is a block copolymer. [0327] In some implementations, the macrodiol includes a poly(isobutylene-co-isoprene) component, wherein the isobutylene portion is present in an amount of 1-99 wt.% relative to the isoprene portion. In some implementations, the isobutylene portion is present in an amount from 1-25 wt.%, from 25-50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25- 75 wt.%, relative to the isoprene. It is understood that the poly(isobutylene-co-isoprene) component can be present in any value that falls within the disclosed ranges. [0328] In some implementations, the macrodiol includes a poly(isobutylene-co-isoprene) component, wherein the isobutylene portion is present in an amount of 90-99.9 wt.% relative to the isoprene portion. In some implementations, the isobutylene portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99- 99.99 wt.%, relative to the isoprene. It is understood that the poly(isobutylene-co-isoprene) component can be present in any value that falls within the disclosed ranges. [0329] In some implementations, the isobutylene portion is present in an amount of 90% by weight relative to the isoprene portion. In some implementations, the isobutylene portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the isoprene. It is understood that the isobutylene portion can be in any range that can be formed by the disclosed above values relative to the isoprene. [0330] In some implementations, the isobutylene portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2.5 wt.%, 1 wt.%, or 0.5 wt.%, relative to the isoprene portion. It is understood that the isobutylene portion can be in any range that can be formed by the disclosed above values relative to the isoprene. [0331] In some implementations, the macrodiol includes a poly(alkylene) component. In some implementations, the poly(alkylene) is a polyethylene, polypropylene, poly(ethylene- co-propylene) polymer. In certain implementations, the poly(alkylene) is block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In certain implementations, the poly(alkylene) is a random copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0332] In some implementations, the poly(alkylene) portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations the poly(alkylene) portion is present in an amount from 1-25 wt.%, from 25- 50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(alkylene) portion can be present in any value that falls within the disclosed ranges. [0333] In some implementations, the poly(alkylene) portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(alkylene) portion can be present in any value that falls within the disclosed ranges. [0334] In some implementations, the poly(alkylene) portion is present in an amount from 1- 10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(alkylene) portion can be present in any value that falls within the disclosed ranges. [0335] In some implementations, the poly(alkylene) portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0336] In some implementations, the poly(alkylene) portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(alkylene) portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene- co-isoprene) portion. [0337] In some implementations, the poly(alkylene) portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the poly(alkylene) portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2 wt.%,1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(alkylene) portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0338] In some implementations, the macrodiol includes a poly(meth)acrylate portion. In some implementations, the poly(meth)acrylate is derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec- butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof. In certain implementations, the poly(meth)acrylate is a block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component. In certain implementations, the poly(meth)acrylate is a random copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component. [0339] In some implementations, the poly(meth)acrylate portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the poly(meth)acrylate portion is present in an amount from 1-25 wt.%, from 25-50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0340] In some implementations, the poly(meth)acrylate portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(meth)acrylate portion can be present in any value that falls within the disclosed ranges. [0341] In some implementations, the poly(meth)acrylate portion is present in an amount from 1-10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(meth)acrylate portion can be present in any value that falls within the disclosed ranges. [0342] In some implementations, the poly(meth)acrylate portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0343] In some implementations, the poly(meth)acrylate portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co- isoprene) portion. It is understood that the poly(meth)acrylate portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0344] In some implementations, the poly(meth)acrylate portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the poly(meth)acrylate portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%,10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(meth)acrylate portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0345] In some implementations, the macrodiol includes a poly(siloxane) component in addition to the polyisobutylene segment. In some implementations, the poly(siloxane) is a poly(dimethylsiloxane), a poly(vinyl-methylsiloxane), or a poly(divinylsiloxane. In certain implementations, the poly(siloxane) is a block copolymer with the poly(isobutylene) or poly(isobutylene-co-isoprene) component. [0346] In some implementations, the poly(siloxane) portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations the poly(siloxane) portion is present in an amount from 1-25 wt.%, from 25- 50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be present in any value that falls within the disclosed ranges. [0347] In some implementations, the poly(siloxane) portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be present in any value that falls within the disclosed ranges. [0348] In some implementations, the poly(siloxane) portion is present in an amount from 1- 10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be present in any value that falls within the disclosed ranges. [0349] In some implementations, the poly(siloxane) portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0350] In some implementations, the poly(siloxane) portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene- co-isoprene) portion. [0351] In some implementations, the poly(siloxane) portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the poly(siloxane) portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the poly(siloxane) portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0352] In some implementations, the macrodiol includes a polyethylene glycol component in addition to the polyisobutylene segment. In some implementations, the polyethylene glycol has a molecular weight (in Daltons) from 100-100,000, from 500-10,000, from 1,000- 50,000, from 500-2,500, from 2,500-7,500, from 5,000-10,000, from 10,000-25,000, from 25,000-50,000, or from 50,000-100,000. It is understood that the polyethylene glycol can have any molecular weight that falls within any two disclosed above values. [0353] In some implementations, the polyethylene glycol portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the polyethylene glycol portion is present in an amount from 1-25 wt.%, from 25-50 wt.%, from 50-75 wt.%, from 75-99 wt.%, or from 25-75 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be present in any value that falls within the disclosed ranges. [0354] In some implementations, the polyethylene glycol portion is present in an amount from 90-95 wt.%, from 95-99 wt.%, from 95-97 wt.%, from 97-99 wt.%, or from 99-99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be present in any value that falls within the disclosed ranges. [0355] In some implementations, the polyethylene glycol portion is present in an amount from 1-10 wt.%, from 5-15 wt.%, from 10-25 wt.%, from 1-5 wt.%, or from 1-2 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be present in any value that falls within the disclosed ranges. [0356] In some implementations, the polyethylene glycol portion is present in an amount of 90% by weight to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0357] In some implementations, the polyethylene glycol portion is present in an amount of 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, 99 wt.%, 99.5 wt.%, 99.9 wt.%, or 99.99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co- isoprene) portion. It is understood that the polyethylene glycol portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0358] In some implementations, the polyethylene glycol portion is present in an amount of 90% by weight relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. In some implementations, the polyethylene glycol portion is present in an amount of 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 20 wt.%, 10 wt.%, 5 wt.%, 2 wt.%, 1 wt.%, or 0.5 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. It is understood that the polyethylene glycol portion can be in any range that can be formed by the disclosed above values relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0359] In certain aspects, the macrodiol segment can have the formula: HO-[-(A1)d-(A2)e-(A3)f-(A4)g-(A5)h-(A6)peg]-OH, wherein A1 is (isobutylene), and d is 1-10,000; A2 is C4-20alkenyl, and e is 0-500; A3 is C4-20alkynyl, and f is 0-500; A4 is C2-20alkyl, and g is 0-10,000; A5 is a siloxane, and h is 0-10,000; A6 is a polyethylene glycol, and peg is 0-10,000 wherein d, e, f, g, h, and peg represent the number of monomer units. [0360] In certain aspects, the macrodiol can have the formula: HO-[-(A1)d’-(A2)e’-(A3)f’-(A4)g’-(A5)h’-(A6)peg’]-OH, wherein A1, A2, A3, A4, A5, and A6 are as defined above, and d’ is 1-100; e’ is 0-99; f’ is 0-99; g’ is 0-99; h’ is 0-99; and peg’ is 0-99, wherein d’ + e’ + f’ + g’ + h’ + peg’ = 100; and d’, e’, f’, g’, h’, and peg’ represent the wt.% of each component in the macrodiol. [0361] In some implementations, A4 is a mixture of (ethylene) and (propylene), while in other aspects, A4 is (ethylene). [0362] In some implementations, A2 is (1,3-butadiene), (2,3-dimethyl-1,3-butadine), (isoprene), or a combination thereof. In some implementations, A2 is (isoprene). [0363] In some implementations, A5 is (dimethylsiloxane). [0364] In some implementations, A3 and A6 are absent, i.e., f, f’, peg, and peg’ are all 0. [0365] In some implementations, the macrodiol can be combined with a diisocyanate that includes a compound of Formula (1a): [Formula (1a)], wherein R1* is a
Figure imgf000077_0001
R1* groups include: ,
Figure imgf000077_0002
, or t includes a compound of Formula (2a): [Formula (2a)], wherein R2* is an
Figure imgf000078_0001
R2* groups include: , . [0367] In
Figure imgf000078_0002
that includes a compound of Formula (3a): [Formula (3a)], wherein R3* is a C
Figure imgf000078_0003
6-30 the context R3*, the C6-30 aromatic group refers to a divalent fragment in which each carbon atom in the shortest sequence of atoms from one nitrogen to the next is part of an aromatic system. Such systems may include sp3 hybridized carbons, so long as such carbons are not part of the shortest path from one nitrogen to the next. Exemplary R3 groups include: .
Figure imgf000078_0004
Chain extender compound [0368] In some implementations, the macrodiol and diisocyanate can be combined with a chain extender compound of Formula (4a): [Formula (4a)], X1 is O or NH; X2 is O or NH; R4* is a saturated C2-30 group. [0369] In some implementations, R4* has the structure: *-(CH2)4aX4a(CH2)4b-#, wherein * represents the point of attachment to X1 and # represents the point of attachment to X2; X4a is null, CHR4a, C(R4a)2,O, NH, or NCH3; R4a is independently C1-8alkyl; 4a is 0-12; and 4b is 0-12, wherein when X4a is null, O, NH, or NCH3, the sum of 4a and 4b is at least 2, and when X4a is CHR4a, the sum of 4a and 4b is at least 1. [0370] In some implementations, X1 is O or NH, X2 is NH, X4a is O, 4a is 2-12, and 4b is 0. [0371] In certain implementations, 4a is 2-12, X4a is null, and 4b is 0. [0372] In certain implementations, one of 4a and 4b is 1, and the other of 4a and 4b is 0, and X4a is CHR4a. [0373] In some implementations, X4a is C(CH3)2. [0374] In some implementations, the macrodiol and diisocyanate can be combined with a chain extender compound of Formula (5a): [Formula (5a)], X3 is O or NH; X4 is O or NH; R5* is an unsaturated C2-30 group. [0375] In some aspects, R5* has the structure: *-(CH2)5aX5a(CH2)5b-#, wherein * represents the point of attachment to X3 and # represents the point of attachment to X4; X5a is CHR5a, C(R5a)2, -CH=CH-, or -C≡C-, R5a is, in each case, independently a C2-12 group, wherein when two of R5a are present, at least one of R5a is an unsaturated C2-12 group; 5a is 0-12; and 5b is 0-12, wherein when X5a is CH=CH-, or -C≡C-, then 5a is 1-12, and 5b is 1-12, and when X5a is CHR5a, the sum of 5a and 5b is at least 1. [0376] In some implementations, 5a is 1-12, 5b is 1-12, and X5a is -CH=CH-. [0377] In some implementations, one of 5a and 5b is 1, and the other of 5a and 5b is 0, and X5a is CHR5a. [0378] In some implementations, R5a is C2-4alkenyl, for example, allyl or vinyl. [0379] In some implementations, the diisocyanate only includes a compound of Formula (4a) and does not include a compound of Formula (5a). In some implementations, the diisocyanate only includes a compound of Formula (5a) and does not include a compound of Formula (4a). In some implementations, the diisocyanate can include a mixture of Formula (4a) and Formula (5a). The diisocyanate can include a compound of Formula (4a) in an amount from 1-99% relative to the compound of Formula (5a). In the context of Formulas (4a) and (5a), the ratio refers to the mole ratio of the compounds of Formula (4a) and (5a) [0380] In some implementations, the diisocyanate can include the compound of Formula (4a) in an amount from 1-25%, from 10-25%, from 25-50%, from 50-75%, from 75-99%, or from 90-99%, relative to the compound of Formula (5a). In some implementations, the diisocyanate can include the compound of Formula (4a) in an amount that is 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 85% relative to the compound of Formula (5a). [0381] In some implementations, the diisocyanate can include the compound of Formula (4a) in an amount from 90-99.99%, from 90-95%, from 95-99%, from 95-97%, from 97- 99%, or from 98-99%, relative to the compound of Formula (5a). In some implementations, the diisocyanate can include the compound of Formula (4a) in an amount that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% relative to the compound of Formula (5a). [0382] In some implementations, when the diisocyanate includes the compound of Formula (5a), the macrodiol will not include a poly(alkenyl) component. In other implementations, when the diisocyanate does not include a compound of Formula (5a), the macrodiol does include a poly(alkenyl) component, e.g., poly(isoprene). [0383] In some implementations, the macrodiol and diisocyanate can be combined with a chain extender that includes a compound of Formula (6a): [Formula (6a)], wherein
Figure imgf000081_0001
X6 is O or NH; X7 is O or NH; R6* is a C2-30 aromatic group. As used in the context R6*, the C6-30 aromatic group refers to a divalent fragment in which each carbon atom in the shortest sequence of atoms from X6 to X7 is part of an aromatic system. Such systems may include sp3 hybridized carbons, so long as such carbons are not part of the shortest path from X6 to X7. [0384] After forming a polyurethane from the macrodiol, diisocyanate, and chain extender compounds, the polyurethane may then be combined with a chain connecter that includes a compound of Formula (7a): [Formula (7a)], 8
Figure imgf000081_0002
X is O or NH; X9 is O or NH; R7* is an unsaturated C2-30 group. [0385] In certain implementations, X8 and X9 are both O, and R7* is an unsaturated C4-10 group having a single unsaturated carbon-carbon bond. Exemplary R7* groups include: or
Figure imgf000082_0001
point of attachment to X9. [0386] In certain aspects, the polyurethane is not combined with a chain connector. For implementations where the polyurethane is combined with a chain connector, the chain connector may be present in an amount that is from 1-99% relative to polyurethane. In this context, the ratio refers to the mass of the polyurethane and the chain connector. [0387] In some implementations, the polyurethane can be present in an amount that is from 1-25%, from 10-25%, from 25-50%, from 50-75%, from 75-99%, or from 90-99%, relative to chain connector. In some implementations, the polyurethane can be present in an amount that is 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 85% relative to the chain connector. [0388] In some implementations, the polyurethane can be present in an amount from 90- 99.99%, from 90-95%, from 95-99%, from 95-97%, from 97-99%, or from 98-99%, relative to the chain connector. In some implementations, the polyurethane can be present in an amount that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% relative to the chain connector. [0389] In still further aspects, the disclosed herein polyurethanes can have a different degree of branching. In certain aspects, the degree of branching of the polyurethanes can be varied from 0 to 99 % of the total polymer composition, including exemplary values of 0.5 %, 1 %, 5 %, 10 %, 15 %, 20 %, 25 %, 30 %, 35 %, 40 %, 45 %, 50 %, 55 %, 60 %, 65 %, 70 %, 75 %, 80 %, 85 %, 90 %, and 95 %. In yet still further aspects, the degree of branching of the disclosed herein polyurethanes is from 0 to 20 %, including exemplary values of 1 %, 2 %, 3 %, 4 %, 5 %, 6 %, 7 %, 8 %, 9 %, 10 %, 11 %, 12 %, 13 %, 14 %, 15 %, 16 %, 17 %, 18 % and 19 %. [0390] Without wishing to be bound by any theory, it is understood that the lower degree of branching can make the polyurethane more crystalline and thus enhance the tensile strength and hence biostability of the polyurethane. Higher degree of branching, on the other hand, is hypothesized to enhance the elasticity and softness of the polyurethane. Pharmaceutically active ingredients [0391] In some implementations, the polymer compositions disclosed herein can also comprise pharmaceutically active ingredients. It is understood that the term “pharmaceutically active ingredients” refers to the components that have a pharmaceutical activity that can affect the subject’s body performance. It is understood that the terms “pharmaceutically active ingredients,” “therapeutic agents,” “drugs,” and “medicine” are used interchangeably. In certain implementations, the compositions disclosed herein comprise one or more pharmaceutically active ingredients. In such implementations, the one or more pharmaceutically active ingredients can be included as a coating of the component formed from the disclosed herein polymer composition, or within (e.g., blended with) the polymer composition, or attached to (e.g., covalently or non-covalently bound to) polymer composition. [0392] It is understood that in the disclosed aspects, a wide variety of pharmaceutically active ingredients can be employed, including those used for the treatment of a wide variety of diseases and conditions (i.e., the prevention of a disease or condition, the reduction or elimination of symptoms associated with a disease or condition, or the substantial or complete elimination of a disease or condition). [0393] In certain aspects, the exemplary the pharmaceutically active ingredients can include but are not limited to (a) anti-thrombotic agents such as heparin, heparin derivatives, urokinase, clopidogrel, and PPack (dextrophenylalanine proline arginine chloromethylketone); (b) anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine and mesalamine; (c) antineoplastic/antiproliferative/anti-miotic agents such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin, angiopeptin, monoclonal antibodies capable of blocking smooth muscle cell proliferation, and thymidine kinase inhibitors; (d) anesthetic agents such as lidocaine, bupivacaine and ropivacaine; (e) anti- coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, hirudin, antithrombin compounds, platelet receptor antagonists, anti- thrombin antibodies, anti-platelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet peptides; (f) vascular cell growth promoters such as growth factors, transcriptional activators, and translational promotors; (g) vascular cell growth inhibitors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; (h) protein kinase and tyrosine kinase inhibitors (e.g., tyrphostins, genistein, quinoxalines); (i) prostacyclin analogs; (j) cholesterol-lowering agents; (k) angiopoietins; (l) antimicrobial agents such as triclosan, cephalosporins, aminoglycosides and nitrofurantoin; (m) cytotoxic agents, cytostatic agents and cell proliferation affectors; (n) vasodilating agents; (o) agents that interfere with endogenous vasoactive mechanisms; (p) inhibitors of leukocyte recruitment, such as monoclonal antibodies; (q) cytokines; (r) hormones; (s) inhibitors of HSP 90 protein (i.e., Heat Shock Protein, which is a molecular chaperone or housekeeping protein and is needed for the stability and function of other client proteins/signal transduction proteins responsible for growth and survival of cells) including geldanamycin, (t) alpha receptor antagonist (such as doxazosin, Tamsulosin) and beta receptor agonists (such as dobutamine, salmeterol), beta receptor antagonist (such as atenolol, metaprolol, butoxamine), angiotensin-II receptor antagonists (such as losartan, valsartan, irbesartan, candesartan and telmisartan), and antispasmodic drugs (such as oxybutynin chloride, flavoxate, tolterodine, hyoscyamine sulfate, diclomine) (u) bARKct inhibitors, (v) phospholamban inhibitors, (w) Serca 2 gene/protein, (x) immune response modifiers including aminoquizolines, for instance, imidazoquinolines such as resiquimod and imiquimod, (y) human apolioproteins (e.g., AI, AII, AIII, AIV, AV, etc.), (z) selective estrogen receptor modulators (SERMs) such as raloxifene, lasofoxifene, arzoxifene, miproxifene, ospemifene, PKS 3741, MF 101 and SR 16234, (aa) PPAR agonists, including PPAR-alpha, gamma and delta agonists, such as rosiglitazone, pioglitazone, netoglitazone, fenofibrate, bexaotene, metaglidasen, rivoglitazone and tesaglitazar, (bb) prostaglandin E agonists, including PGE2 agonists, such as alprostadil or ONO 8815Ly, (cc) thrombin receptor activating peptide (TRAP), (dd) vasopeptidase inhibitors including benazepril, fosinopril, lisinopril, quinapril, ramipril, imidapril, delapril, moexipril and spirapril, (ee) thymosin beta 4, (ff) phospholipids including phosphorylcholine, phosphatidylinositol and phosphatidylcholine, (gg) VLA-4 antagonists and VCAM-1 antagonists, (hh) non-fouling, protein resistant agents such as polyethyelene glycol and (ii) prohealing agents. [0394] Where pharmaceutically active ingredients are present, a wide range of loadings may be used in conjunction with the medical devices of the present invention. Typical pharmaceutically active ingredient loadings range, for example, from 0.001 wt.% to 25 wt.% of the total polymer composition, including exemplary values of 0.005 wt.%, 0.01 wt.%, 0.05 wt.%, 0.1 wt.%, 0.5 wt.%, 1 wt.%, 2 wt.%, 3 wt.%, 4 wt.%, 5 wt.%, 6 wt.%, 7 wt.%, 8 wt.%, 9 wt.%, 10 wt.%, 11 wt.%, 12 wt.%, 13 wt.%, 14 wt.%, 15 wt.%, 16 wt.%, 17 wt.%, 18 wt.%, 19 wt.%, 20 wt.%, 21 wt.%, 22 wt.%, 23 wt.%, and 24 wt.%. DEVICES [0395] The disclosed herein materials are engineered to provide improved biostability, fatigue resistance and the desired flexibility, elasticity and softness that can be used in insertable and implantable medical devices. The polymeric materials disclosed herein can be extruded as films, coatings, fibers, or any combination thereof. In yet other aspects, the polymeric materials disclosed herein can be extruded into any desired shape or form. In yet still further aspects, the polymeric materials disclosed herein can be molded to any desired shape or form. In yet still further aspects, the disclosed herein compositions can be used for electrospinning of the fibers. [0396] In certain aspects, the devices disclosed herein can have at least a portion comprising any of the disclosed herein polymeric compositions. In still further aspects, a substantial portion of the medical device can comprise any of the disclosed herein polymeric compositions. [0397] In certain aspects, the devices disclosed herein and comprising any of the disclosed herein compositions are insertable and/or implantable medical devices. In certain aspects, the devices disclosed herein are implantable medical devices that are configured to stay in a subject’s body for a predetermined period of time without substantially changing. In certain aspects, the predetermined period of time is greater than one week, greater than 1 month, greater than 6 months, greater than 1 year, greater than 5 years, greater than 10 years, greater than 15 years, greater than 20 years, greater than 30 years, greater than 40 years or even greater than 50 years. In yet still further aspects, the predetermined period of time is at least 1 day, at least 1 week, at least 1 month, at least 6 months, at least 1 year, at least 5 years, at least 10 years, at least 15 years, or at least 20 years. [0398] In some exemplary and unlimiting aspects, the device comprising any of the disclosed herein composition are implantable heart valves. [0399] An exemplary and unlimiting device is shown in FIG.1. FIG.1 shows a prosthetic heart valve 10, according to one aspect. The illustrated prosthetic valve is adapted to be implanted in the native aortic annulus, although in other aspects, it can be adapted to be implanted in the other native annuluses of the heart (e.g., the pulmonary, mitral, and tricuspid valves). The prosthetic valve can also be adapted to be implanted in other tubular organs or passageways in the body. The prosthetic valve 10 can have four main components: a stent or frame 12, a valvular structure 14, an inner skirt 16, and an exemplary perivalvular outer sealing member or outer skirt 18. The exemplary prosthetic valve 10 has an inflow end portion 15, an intermediate portion 17, and an outflow end portion 19. The outer sealing member 18 has a proximal end 1802 and a distal end 1804 and is mounted circumferentially around a first portion of the outer surface of the annular frame 12, wherein the first portion 1806 of the outer surface has a proximal end and a distal end, wherein the proximal end of the first portion is at the inflow end 15 of the annular frame 12. In aspects disclosed herein, for example, the first portion 1806 of the annular frame can be between the inflow end 15 of the annular frame and the beginning of the intermediate portion 17. The first portion, 1806, is also defined by a proximal end 1806a and a distal end 1806b. [0400] In still further aspects, the annular frame also has a second portion 1820 that is free of the outer sealing member and extends between the outflow end 19 of the annular frame and the distal end of the first portion 1806b. [0401] The bare frame 12 is shown in FIG.2. Frame 12 can be formed with a plurality of circumferentially spaced slots or commissure windows, 20 (three are shown in the illustrated and unlimiting aspect) that are adapted to mount the commissures of the valvular structure 14 to the frame, as described in greater detail below. The frame 12 can be made of any of various suitable plastically-expandable materials (e.g., stainless steel, etc.) or self- expanding materials (e.g., nickel-titanium alloy (NiTi), such as nitinol) as known in the art. When constructed of a plastically-expandable material, frame 12 (and thus the prosthetic valve 10) can be crimped to a radially collapsed configuration on a delivery catheter and then expanded at the implantation site by an inflatable balloon or equivalent expansion mechanism. When constructed of a self-expandable material, frame 12 (and thus the prosthetic valve 10) can be crimped to a radially collapsed configuration and restrained in the collapsed configuration by insertion into a sheath or equivalent mechanism of a delivery catheter. Once inside the body, the prosthetic valve can be advanced from the delivery sheath, which allows the prosthetic valve to expand to its functional size. [0402] Suitable plastically-expandable materials that can be used to form the frame 12 include, without limitation, stainless steel, biocompatible, high-strength alloys (e.g., a cobalt-chromium or nickel-cobalt-chromium alloys), polymers, or combinations thereof. In particular aspects, frame 12 is made of a nickel-cobalt-chromium-molybdenum alloy, such as MP35N® alloy (SPS Technologies, Jenkintown, Pa.), which is equivalent to UNS R30035 alloy (covered by ASTM F562-02). MP35N® alloy/UNS R30035 alloy comprises 35% nickel, 35% cobalt, 20% chromium, and 10% molybdenum by weight. It has been found that the use of MP35N® alloy to form frame 12 provides superior structural results over stainless steel. In particular, when MP35N® alloy is used as the frame material, less material is needed to achieve the same or better performance in radial and crush force resistance, fatigue resistance, and corrosion resistance. Moreover, since less material is required, the crimped profile of the frame can be reduced, thereby providing a lower-profile prosthetic valve assembly for percutaneous delivery to the treatment location in the body. [0403] Referring to FIGS.2 and 3, frame 12 in the illustrated aspect comprises a first, lower row I of angled struts 22 arranged end-to-end and extending circumferentially at the inflow end of the frame; a second row II of circumferentially extending angled struts 24; a third row III of circumferentially extending, angled struts 26; a fourth row IV of circumferentially extending angled struts 28; and a fifth row V of circumferentially extending, angled struts 32 at the outflow end of the frame. A plurality of substantially straight axially extending struts 34 can be used to interconnect the struts 22 of the first row I with the struts 24 of the second row II. The fifth row V of angled struts 32 are connected to the fourth row IV of angled struts 28 by a plurality of axially extending window frame portions 30 (which define the commissure windows 20) and a plurality of axially extending struts 31. Each axial strut 31 and each frame portion 30 extends from a location defined by the convergence of the lower ends of two angled struts 32 to another location defined by the convergence of the upper ends of two angled struts 28. [0404] Each commissure window frame portion 30 mounts a respective commissure of the leaflet structure 14. As can be seen, each frame portion 30 is secured at its upper and lower ends to the adjacent rows of struts to provide a robust configuration that enhances fatigue resistance under cyclic loading of the prosthetic valve compared to known, cantilevered struts for supporting the commissures of the leaflet structure. This configuration enables a reduction in the frame wall thickness to achieve a smaller crimped diameter of the prosthetic valve. In certain aspects, the thickness T of frame 12 (FIG.2) measured between the inner diameter and outer diameter is 0.48 mm or less. [0405] The struts and frame portions of the frame collectively define a plurality of open cells of the frame. At the inflow end of frame 12, struts 22, struts 24, and struts 34 define a lower row of cells defining openings 36. The second, third, and fourth rows of struts 24, 26, and 28 define two intermediate rows of cells defining openings 38. The fourth and fifth rows of struts 28 and 32, along with frame portions 30 and struts 31, define an upper row of cells defining openings 41. The openings 41 are relatively large and are sized to allow portions of the leaflet structure 14 to protrude, or bulge, into and/or through the openings 41 when the frame 12 is crimped in order to minimize the crimping profile. [0406] Frame 12 is configured to reduce, prevent, or minimize possible over-expansion of the prosthetic valve at a predetermined balloon pressure, especially at the outflow end portion of the frame, which supports the leaflet structure 14. In one aspect, the frame is configured to have relatively larger angles 42a, 42b, 42c, 42d, 42e between struts, as shown in FIG.3. The larger the angle, the greater the force required to open (expand) the frame. As such, the angles between the struts of the frame can be selected to limit the radial expansion of the frame at a given opening pressure (e.g., inflation pressure of the balloon). In some exemplary aspects, these angles are at least 110 degrees or greater when the frame is expanded to its functional size, and even more particularly, these angles are up to 120 degrees when the frame is expanded to its functional size. [0407] In addition, the inflow 15 and outflow 19 ends of a frame generally tend to over- expand more so than the middle portion of the frame due to the “dog-boning” effect of the balloon used to expand the prosthetic valve. To protect against over-expansion of the leaflet structure 14, the leaflet structure desirably is secured to the frame 12 below the upper row of struts 32, as best shown in FIG.1. Thus, in the event that the outflow end of the frame is over-expanded, the leaflet structure is positioned at a level below where over-expansion is likely to occur, thereby protecting the leaflet structure from over-expansion. [0408] The valvular structure 14 can comprise three leaflets 40 (FIG.4), collectively forming a leaflet structure, which can be arranged to collapse in a tricuspid arrangement. In certain aspects, the leaflets can be formed from the disclosed herein polymer compositions. In such aspects, the polymer composition can exhibit a tensile strength from 30 MPa to 40 MPa, including exemplary values of 31 MPa, 32 MPa, 33 MPa, 34 MPa, 35 MPa, 36 MPa, 37 MPa, 38 MPa, and 39 MPa. In yet still further aspects, the leaflets can exhibit a tensile strength having any values between any foregoing values or within a range formed by any of the foregoing values. For example, the leaflets can exhibit a tensile strength from 30 MPa to 37 MPa, or 30 MPa to 35 MPa, or 30 MPa to 32 MPa, or 32 MPa to 40 MPa, and so on. [0409] In yet still further aspects, the leaflets formed from the disclosed herein compositions can have an elastic modulus from 15 MPa to 25 MPa, including exemplary values of 16 MPa, 17 MPa, 18 MPa, 19 MPa, 20 MPa, 21 MPa, 22 MPa, 23 MPa, and 24 MPa. In yet still further aspects, the leaflets can exhibit an elastic modulus having any values between any foregoing values. In yet still further aspects, the leaflets can exhibit the elastic modulus having any values between any foregoing values or within a range formed by any of the foregoing values. For example, the leaflets can exhibit a elastic modulus from 16 MPa to 24 MPa, or 16 MPa to 22 MPa, or 16 MPa to 20 MPa, or 16 MPa to 18 MPa, or 18 MPa to 25 MPa, and so on. [0410] In yet still further aspects, the leaflets formed from the disclosed herein compositions can exhibit elongation greater than 100%, greater than 200%, greater than 300%, greater than 400%, or greater 500%. In yet still further aspects, the leaflets formed from the disclosed herein compositions can exhibit elongation of at least 500%, at least 400%, at least 300%, or at least 100%. [0411] The leaflets 40 of the leaflet structure 14 formed from the disclosed herein polymer composition can have an undulating, curved scalloped shape (suture line 154 shown in FIG. 6 tracks the scalloped shape of the leaflet structure). By forming the leaflets with this scalloped geometry, stresses on the leaflets are reduced, which in turn improves the durability of the prosthetic valve. Moreover, by virtue of the scalloped shape, folds and ripples at the belly of each leaflet (the central region of each leaflet), which can cause early calcification in those areas, can be eliminated or at least minimized. The scalloped geometry also reduces the amount of tissue material used to form leaflet structure, thereby allowing a smaller, more even crimped profile at the inflow end of the prosthetic valve. [0412] In some aspects, in a prosthetic valve construction, portions of the leaflets can protrude longitudinally beyond the outflow end of the frame when the prosthetic valve is crimped if the leaflets are mounted too close to the distal end of the frame. If the delivery catheter on which the crimped prosthetic valve is mounted includes a pushing mechanism or stop member that pushes against or abuts the outflow end of the prosthetic valve (for example, to maintain the position of the crimped prosthetic valve on the delivery catheter), the pushing member or stop member can damage the portions of the exposed leaflets that extend beyond the outflow end of the frame. Another benefit of mounting the leaflets at a location spaced away from the outflow end of the frame is that when the prosthetic valve is crimped on a delivery catheter, the outflow end of the frame 12 rather than the leaflets 40 is the proximal-most component of the prosthetic valve 10. As such, if the delivery catheter includes a pushing mechanism or stop member that pushes against or abuts the outflow end of the prosthetic valve, the pushing mechanism or stop member contacts the outflow end of the frame, and not leaflets 40, so as to avoid damage to the leaflets. [0413] Also, as can be seen in FIG.3, the openings 36 of the lowermost row of openings in the frame are relatively larger than the openings 38 of the two intermediate rows of openings. This allows the frame, when crimped, to assume an overall tapered shape that tapers from a maximum diameter at the outflow end of the prosthetic valve to a minimum diameter at the inflow end of the prosthetic valve. When crimped, frame 12 has a reduced diameter region extending along a portion of the frame adjacent the inflow end of the frame that generally corresponds to the region of the frame covered by the outer skirt 18. In some aspects, the reduced diameter region is reduced compared to the diameter of the upper portion of the frame (which is not covered by the outer skirt) such that the outer skirt 18 does not increase the overall crimp profile of the prosthetic valve. When the prosthetic valve is deployed, the frame can expand to the generally cylindrical shape shown in FIG.3. In one example, the frame of a 26-mm prosthetic valve, when crimped, had a first diameter of 14 French at the outflow end of the prosthetic valve and a second diameter of 12 French at the inflow end of the prosthetic valve. [0414] In still further aspects, the polymer compositions disclosed herein can be used to form an inner skirt 16. It is understood that the inner skirt can be formed as a film of the desired thickness, or it can be used as a textile. It is understood that if the inner skirt is a textile material, this textile material can be woven or knitted. In certain aspects, the inner skirt is a woven textile. In such aspects, one or more warp yarns comprise one or more fibers comprising the disclosed herein composition. In yet other aspects, one or more weft yarns can comprise one or more fibers comprising the disclosed herein composition. In yet still further aspects, one or more warp yarns and one or more weft yarns can comprise fibers comprising the disclosed herein composition. [0415] In the aspects where the inner skirt is formed as a textile, the disclosed herein composition can be extruded (or electrospinned) to form the fibers that are then used to form the textile of the inner skirt. In the aspects where the disclosed herein compositions used to form the inner skirt, the formed textiles and/or films can exhibit a tensile strength of 100 MPa to 200 MPa, including exemplary values of 110 MPa, 120 MPa, 130 MPa, 140 MPa, 150 MPa, 160 MPa, 170 MPa, 180 MPa, and 190 MPa. In yet still further aspects, the formed textiles and/or films can exhibit a tensile strength having any values between any foregoing values or within a range formed by any of the foregoing values. For example, the formed textiles and/or films comprising the disclosed herein polymer compositions can exhibit a tensile strength from 100 MPa to 180 MPa, or 100 MPa to 150 MPa, or 100 MPa to 130 MPa, or 140 MPa to 200 MPa, and so on. [0416] In still further aspects, the formed textiles and/or films can exhibit an elastic modulus from 50 MPa to 150 MPa, including exemplary values of 60 MPa, 70 MPa, 80 MPa, 90 MPa, 100 MPa, 110 MPa, 120 MPa, 130 MPa, and 140 MPa. In yet still further aspects, the formed textiles and/or films can exhibit an elastic modulus having any values between any foregoing values or within a range formed by any of the foregoing values. For example, the formed textiles and/or films comprising the disclosed herein polymer compositions can exhibit an elastic modulus from 50 MPa to 130 MPa, or 50 MPa to 100 MPa, or 50 MPa to 80 MPa, or 70 MPa to 150 MPa, and so on. [0417] In still further aspects, the formed textiles and/or films can exhibit elongation of 100 % to 150 %, including exemplary values of 105 %, 110 %, 115 %, 120 %, 125 %, 130 %, 135 %, 140 %, and 145 %. In yet still further aspects, the formed textiles and/or films can exhibit elongation having any values between any foregoing values or within a range formed by any of the foregoing values. For example, the formed textiles and/or films comprising the disclosed herein polymer compositions can exhibit elongation from 100 % to 130 %, or 100 % to 135 %, 100 % to 120 % or 100 % to 110 %, or 110 % to 140 %, and so on. [0418] The main functions of the inner skirt 16 are to assist in securing the valvular structure 14 to the frame 12 and to assist in forming a good seal between the prosthetic valve and the native annulus by blocking the flow of blood through the open cells of the frame 12 below the lower edge of the leaflets. The thickness of the skirt is desirably less than 0.15 mm (6 mil), and desirably less than 0.1 mm (4 mil), and even more desirably 0.05 mm (2 mil). In certain exemplary and unlimiting aspects, inner skirt 16 can have a variable thickness, for example, the skirt can be thicker at at least one of its edges than at its center. In one implementation, inner skirt 16 can comprise a skirt formed from the disclosed herein compositions and having a thickness of 0.07 mm at its edges and 0.06 mm at its center. The thinner skirt can provide for better crimping performances while still providing good perivalvular sealing. [0419] The inner skirt 16 can be secured to the inside of frame 12 via sutures 70, as shown in FIG.6. Valvular structure 14 can be attached to the skirt via one or more reinforcing strips 72 (FIG.7) (which collectively can form a sleeve), for example, thin, PET reinforcing strips, discussed below, which enables a secure suturing and protects the pericardial tissue of the leaflet structure from tears. Valvular structure 14 can be sandwiched between skirt 16 and the thin PET strips 72, as shown in FIG.7. Sutures 154, which secure the PET strip and the leaflet structure 14 to skirt 16, can be any suitable suture, such as Ethibond Excel® PET suture (Johnson & Johnson, New Brunswick, N.J.). Sutures 154 desirably track the curvature of the bottom edge of leaflet structure 14, as described in more detail below. It is understood, however, that the disclosed herein strips can also be made from the described polymer compositions. [0420] The disclosed herein inner skirt is configured to be elastic enough such that when it elongates along with the frame, no deformation to the struts of the framer occurs, and a uniform crimping is obtained. [0421] The inner skirt 16 can be sutured to frame 12 at locations away from the suture line 154 so that the skirt can be more pliable in that area. This configuration can avoid stress concentrations at the suture line 154, which attaches the lower edges of the leaflets to the inner skirt 16. [0422] As noted above, the leaflet structure 14 in the illustrated aspect includes three flexible leaflets 40 (although a greater or a smaller number of leaflets can be used). [0423] The leaflets 40 can be secured to one another at their adjacent sides to form commissures 122 of the leaflet structure (FIG.6). A plurality of flexible connectors 124 (one of which is shown in FIG.5) can be used to interconnect pairs of adjacent sides of the leaflets and to mount the leaflets to the commissure window frame portions 30 (FIG. 3). FIG.5 shows the adjacent sides of two leaflets 40 interconnected by a flexible connector 124. Three leaflets 40 can be secured to each other side-to-side using three flexible connectors 124, as shown in FIG.4. Additional information regarding connecting the leaflets to each other, as well as connecting the leaflets to the frame, can be found, for example, in U.S. Patent Application Publication No.2012/0123529, which is incorporated by reference herein in its entirety. [0424] As noted above, the inner skirt 16 can be used to assist in suturing the leaflet structure 14 to the frame. The inner skirt 16 can have an undulating temporary marking suture to guide the attachment of the lower edges of each leaflet 40. The inner skirt 16 itself can be sutured to the struts of frame 12 using sutures 70, as noted above, before securing the leaflet structure 14 to the skirt 16. The struts that intersect the marking suture desirably are not attached to the inner skirt 16. This allows the inner skirt 16 to be more pliable in the areas not secured to the frame and minimizes stress concentrations along the suture line that secures the lower edges of the leaflets to the skirt. [0425] In still further aspects, the outer skirt 18 can comprise the disclosed herein compositions. While in other aspects, the outer skirt 18 does not comprise the disclosed herein compositions. In yet still further aspects, the outer skirt 18 can be constructed as known in the art applications, for example and without limitations similarly to the outer skirt disclosed in patent applications, WO/2018/222799 or WO/2006/005015, the entire descriptions of which are incorporated herein by reference. [0426] It is understood that the device disclosed above is only exemplary, and other medical devices can comprise the disclosed herein compositions. For example and without limitations, the disclosed herein medical devices can comprise electrical simulations systems such as spinal cord stimulation (SCS) systems, deep brain stimulation (DBS) systems, peripheral nerve stimulation (PNS) systems, gastric nerve stimulation systems, cochlear implant systems, and retinal implant systems. In yet other aspects, the devices can comprise cardiac systems, including implantable pacemaker systems, implantable cardioverter- defibrillators (ICD’s), and cardiac resynchronization and defibrillation (CRDT) devices. Also the disclosed herein compositions can be included in polymeric components used for leads, including lead insulation, outer body insulation, and components for the foregoing implantable electrical stimulation systems. In still further aspects, the disclosed compositions can be used in stents (including coronary vascular stents, peripheral vascular stents, cerebral, urethral, ureteral, biliary, tracheal, gastrointestinal and esophageal stents), stent coverings, stent-grafts. In yet still further aspects, the disclosed herein compositions can be used as grafts, for example, vascular grafts. In still further aspects, the disclosed herein compositions can be used to form abdominal aortic aneurysm (AAA) devices (e.g., AAA stents, AAA grafts, etc.), vascular access ports, dialysis ports, embolization devices including cerebral aneurysm filler coils (including Guglilmi detachable coils and metal coils) and the like. In still further aspects, the disclosed herein compositions can be used in embolic agents, tissue bulking devices, and catheters. It is understood that the term “catheter” can be used in a broad interpretation and include, without limitations, renal or vascular catheters such as balloon catheters and various central venous catheters. The compositions disclosed herein also can be used in introducers, guide wires, balloons, filters, septal defect closure devices, myocardial plugs, patches, Ventricular assist devices including left ventricular assist hearts and pumps, total artificial hearts, shunts, anastomosis clips and rings, and the like. The disclosed herein compositions can also be utilized in tissue engineering as scaffolds for cartilage, bone, skin and other in vivo tissue regeneration (e.g., porous scaffolds, electrospun films and membranes for tissue integration), urethral slings, hernia "meshes, artificial ligaments, orthopedic prosthesis, one graft, or spinal disks. In still further aspects, the disclosed herein compositions can be used in dental implants. It is understood, and as disclosed above, the compositions disclosed herein can constitute at least one component of any of the disclosed herein devices or the device can be substantially constructed of the disclosed herein compositions. It is further understood that the component constitutes both a coating and a specific element of the device. When the compositions disclosed herein are used as a coating, they coat any other materials present in the device, for example, metals, other polymers, ceramics, or any combinations thereof. EXAMPLES [0427] The following examples are for the purpose of illustration of the disclosure only and are not intended to limit the scope of the present disclosure in any manner whatsoever. [0428] EXAMPLE 1 [0429] To obtain the disclosed herein polyurethane compositions, a saturated polyol of MW 1500-3000 Daltons is combined with any of the disclosed herein chain extenders at room temperature and then degassed under vacuum (2 torrs). Any of the disclosed herein diisocyanates is then added, and the mixture is mixed vigorously at high temperatures (75 °C to 95 °C) under atmospheric pressure for a few hours (3 hrs – 8 hrs). Any of the disclosed herein chain connectors (crosslinkers) can then be added. The reaction is cooled to a lower temperature (40 °C to 60 °C) for a few minutes (10-20 mins). Then the mixture is cooled to room temperature and left for 24-48 hrs. EXAMPLARY ASPECTS [0430] EXEMPLARY ASPECT 1. A crosslinked polyurethane, said crosslinked polyurethane obtained by crosslinking a polyurethane having the formula: wherein a is from [soft] represents a
Figure imgf000095_0001
macrodiol segment comprising a poly(isobutylene) component; [DI] represents a diisocyante component; [CE] represents a chain extender component; [CC] represents a chain connector component, wherein one or more of [soft], [DI], [CE], and [CC] comprises a crosslinkable group. [0431] EXEMPLARY ASPECT 2. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspect 1, wherein the polyurethane has a molecular weight from 50,000 g/mol to 1,000,000 g/mol. [0432] EXEMPLARY ASPECT 3. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-2, wherein the polyurethane has a molecular weight that is from 100,000 g/mol to 300,000 g/mol. [0433] EXEMPLARY ASPECT 4. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-3, wherein the crosslinkable group comprises a carbon-carbon double bond, carbon-carbon triple bond, epoxide, carboxylic acid, activated carboxylic acids, a clickable group, or combination thereof. [0434] EXEMPLARY ASPECT 5. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-4, wherein the crosslinkable group comprises a carbon-carbon double bond. [0435] EXEMPLARY ASPECT 6. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-5, wherein the crosslinkable group comprises a terminal alkyne, azide, or combination thereof. [0436] EXEMPLARY ASPECT 7. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-6, wherein the crosslinkable group comprises an epoxide. [0437] EXEMPLARY ASPECT 8. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-7, wherein [soft] comprises a poly(alkenyl) component. [0438] EXEMPLARY ASPECT 9. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-8, wherein [soft] comprises a poly(1,3- butadiene), poly(2,3-dimethyl-1,3-butadine), or poly(isoprene) component. [0439] EXEMPLARY ASPECT 10. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-9, wherein [soft] comprises a poly(alkynyl) component. [0440] EXEMPLARY ASPECT 11. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-10, wherein [soft] comprises a poly(alkyl) component, wherein the poly(alkyl) is not polyisobutylene. [0441] EXEMPLARY ASPECT 12. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-11, wherein [soft] comprises a poly(ethylene) component. [0442] EXEMPLARY ASPECT 13. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-12, wherein [soft] comprises a poly(ethylene glycol) component. [0443] EXEMPLARY ASPECT 14. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-13, wherein [soft] comprises a poly(isobutylene-co-isoprene) component. [0444] EXEMPLARY ASPECT 15. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-14, wherein the poly(isobutylene-co- isoprene) component is a block copolymer. [0445] EXEMPLARY ASPECT 16. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-15, wherein the poly(isobutylene-co- isoprene) component is a random copolymer. [0446] EXEMPLARY ASPECT 17. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-16, wherein [soft] comprises a poly(isobutylene-co-isoprene) component, wherein the isobutylene portion is present in an amount from 1-99 wt.% relative to the isoprene portion. [0447] EXEMPLARY ASPECT 18. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-17, wherein [soft] comprises a poly(isobutylene-co-ethylene) component. [0448] EXEMPLARY ASPECT 19. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-18, wherein the poly(isobutylene-co- ethylene) component is a block copolymer with the poly(isobutylene) or poly(isobutylene-co- isoprene) portion. [0449] EXEMPLARY ASPECT 20. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-19, wherein the poly(isobutylene-co- ethylene) component is a random copolymer with the poly(isobutylene) or poly(isobutylene- co-isoprene) portion. [0450] EXEMPLARY ASPECT 21. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-20, wherein [soft] comprises a poly(isobutylene-co-ethylene) component, wherein the poly(alkylene) portion is present in an amount of 1-99 wt.%, relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0451] EXEMPLARY ASPECT 22. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-21, wherein [soft] comprises a poly(isobutylene-co-ethylene-co-isoprene) component. [0452] EXEMPLARY ASPECT 23. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-22, wherein the poly(isobutylene-co- ethylene-co-isoprene) component is a block copolymer. [0453] EXEMPLARY ASPECT 24. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-23, wherein the poly(isobutylene-co- ethylene-co-isoprene) component is a random copolymer. [0454] EXEMPLARY ASPECT 25. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-24, wherein [soft] comprises a poly(meth)acrylate component. [0455] EXEMPLARY ASPECT 26. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-25, wherein [soft] comprises a poly(meth)acrylate component, wherein the poly(meth)acrylate portion is present in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0456] EXEMPLARY ASPECT 27. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-26, wherein the poly(meth)acrylate component comprises an oligomer derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec-butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof. [0457] EXEMPLARY ASPECT 28. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-27, wherein [soft] comprises a poly(siloxane) component. [0458] EXEMPLARY ASPECT 29. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-28, wherein [soft] comprises a poly(siloxane) component in an amount of 1-99 wt.% relative to the poly(isobutylene) or poly(isobutylene-co-isoprene) portion. [0459] EXEMPLARY ASPECT 30. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-29, wherein [soft] comprises a poly(dimethylsiloxane), a poly(vinyl-methylsiloxane), or a poly(divinylsiloxane) component. [0460] EXEMPLARY ASPECT 31. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-30, wherein [soft] comprises a polyethylene glycol component. [0461] EXEMPLARY ASPECT 32. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-31, wherein the polyethylene glycol component has a molecular weight (in Daltons) from 100-100,000, from 500-10,000, from 1,000-50,000, from 500-2,500, from 2,500-7,500, from 5,000-10,000, from 10,000-25,000, from 25,000-50,000, or from 50,000-100,000. [0462] EXEMPLARY ASPECT 33. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-32, wherein [soft] comprises an oligomer having the formula: -[-(A1)d-(A2)e-(A3)f-(A4)g-(A5)h-(A6)peg]-, wherein A1 is (isobutylene), and d is 1-10,000; A2 is C4-20alkenyl, e is 0-500; A3 is C4-20alkynyl, and f is 0- 500 A4 is C2-20alkyl, and g is 0-10,000; A5 is a siloxane, and h is 0-10,000; A6 is a polyethylene glycol, and peg is 0-10,000; and wherein d, e, f, g, h, and peg represent the number of monomer units. [0463] EXEMPLARY ASPECT 34. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-33, wherein [soft] comprises an oligomer having the formula: -[-(A1)d’-(A2)e’-(A3)f’-(A4)g’-(A5)h’-(A6)peg’]-, wherein A1, A2, A3, A4, A5, and A6 are as defined above, and d' is 1-100; e' is 0-99; f' is 0-99; g' is 0-99; h' is 0-99; and peg' is 0-99, wherein d' + e' + f' + g' + h' + peg' = 100; and d', e', f', g', h', and peg' represent the wt.% of each component in the soft segment. [0464] EXEMPLARY ASPECT 35. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-34, wherein A4 is ethylene or a mixture of (ethylene) and (propylene). [0465] EXEMPLARY ASPECT 36. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-35, wherein A2 is (1,3-butadiene), (2,3- dimethyl-1,3-butadine), (isoprene), or a combination thereof. [0466] EXEMPLARY ASPECT 37. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-36, wherein A2 is (isoprene). [0467] EXEMPLARY ASPECT 38. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-37, wherein A2 has the formula: .
Figure imgf000099_0001
preceding exemplary aspects, particularly Exemplary Aspects 1-38, wherein A5 is (dimethyl)siloxane. [0469] EXEMPLARY ASPECT 40. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-39, wherein A3 and A6 are absent. [0470] EXEMPLARY ASPECT 41. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-40, wherein [soft] is an oligomer having the formula: -[isobutylenyl]i-[isoprenyl]m-[dimethylsiloxane]o-, or -[isobutylenyl]i- [isoprenyl]m-[ethylenyl]n-[ dimethylsiloxane]o-; wherein: i is 1-10,000; n is 1-10,000; m is 1-50; and o is 0-10,000. [0471] EXEMPLARY ASPECT 42. The crosslinked of any preceding exemplary aspects, particularly Exemplary Aspects 1-41, wherein [DI] includes segments of Formula (1): [Formula (1)], wherein the wavy lines represent points of attachment
Figure imgf000100_0001
or [CC], wherein R1 is a saturated C2-30 group. [0472] EXEMPLARY ASPECT 43. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-42, wherein R1 has the formula: or
Figure imgf000100_0002
particularly Exemplary Aspects 1-43, wherein [DI] includes segments of Formula (2): [Formula (2)], wherein the wavy lines represent points of attachment
Figure imgf000100_0003
to any of [soft], [CE], or [CC], wherein R2 is an unsaturated C2-30 group. [0474] EXEMPLARY ASPECT 45. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-44, wherein R2 has the formula: , . thane of any preceding exemplary aspects, particularly Exemplary Aspects 1-44,5wherein [DI] includes segments of Formula (3) [Formula (3)], wherein the wavy lines represent points of
Figure imgf000101_0001
, , or [CC], wherein R3 is a C6-30 aromatic group. [0476] EXEMPLARY ASPECT 47. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-46, wherein R3 has the formula: .
Figure imgf000101_0002
exemplary aspects, particularly Exemplary Aspects 1-47, wherein [CE] includes segments of Formula (4): [Formula (4)], wherein the wavy lines represent points of attachment to [DI], X1 is O or NH; X2 is O or NH; and R4 is a saturated C2-30 group. [0478] EXEMPLARY ASPECT 49. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-48, wherein R4 has the structure: *- (CH2)4aX4a(CH2)4b-#, wherein * represents the point of attachment to X1 and # represents the point of attachment to X2; X4a is null, CHR4a, C(R4a)2, O, NH, or NCH3; R4a is independently C1-8alkyl; 4a is 0-12; and 4b is 0-12, wherein when X4a is null, O, NH, or NCH3 the sum of 4a and 4b is at least 2, and when X4a is CHR4a or C(R4a)2 the sum of 4a and 4b is at least 1. [0479] EXEMPLARY ASPECT 50. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-49, wherein X1 is O or NH, X2 is NH, X4a is O, 4a is 2-12, and 4b is 0. [0480] EXEMPLARY ASPECT 51. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-50, wherein 4a is 2-12, X4a is null, and 4b is 0. [0481] EXEMPLARY ASPECT 52. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-51, wherein one of 4a and 4b is 1, and the other of 4a and 4b is 0, and X4a is CHR4a or C(R4a)2. [0482] EXEMPLARY ASPECT 53. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-52, wherein X4a is C(CH3)2. [0483] EXEMPLARY ASPECT 54. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-53, wherein [CE] includes segments of Formula (5): [Formula (5)], wherein the wavy lines represent points of attachment to [DI], X3 is O or NH; X4 is O or NH; R5 is an unsaturated C2-30 group. [0484] EXEMPLARY ASPECT 55. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-54, wherein R5 has the structure: *- (CH2)5aX5a(CH2)5b-#, wherein * represents the point of attachment to X3 and # represents the point of attachment to X4; X5a is CHR5a, C(R5a)2, -CH=CH-, or -C≡C-, R5a is, in each case, independently a C2-12 group, wherein when two of R5a are present, at least one of R5a is an unsaturated C2-12 group; 5a is 0-12; and 5b is 0-12, wherein when X5a is CH=CH-, or -C≡C-, then 5a is 1-12, and 5b is 1-12, and when X5a is CHR5a, the sum of 5a and 5b is at least 1. [0485] EXEMPLARY ASPECT 56. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-55, wherein 5a is 1-12, including 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11; 5b is 1-12, including 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11, and X5a is - CH=CH-. [0486] EXEMPLARY ASPECT 57. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-56, wherein one of 5a and 5b is 1, and the other of 5a and 5b is 0, and X5a is CHR5a or C(R5a)2. [0487] EXEMPLARY ASPECT 58. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-57, wherein R5a is C2-4alkenyl. [0488] EXEMPLARY ASPECT 59. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-58, wherein [CE] includes segments of Formula (6): [Formula (6)], wherein the wavy lines represent points of attachment to [DI], X6 is O or NH; X7 is O or NH; and C6-30 aromatic group. [0489] EXEMPLARY ASPECT 60. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-59, wherein [CC] is a segment of Formula (7): [Formula (7)], wherein the wavy lines represent points of attachment to [DI], X8 is O or NH; X9 is O or NH; and R7 is an unsaturated C2-30 group. [0490] EXEMPLARY ASPECT 61. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-60, wherein X8 and X9 are both O, and R7 is an unsaturated C4-10 group having a single unsaturated carbon-carbon bond. [0491] EXEMPLARY ASPECT 62. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-61, wherein R7 has the formula: , ,
Figure imgf000103_0001
, wherein wavy line 8 represents the point of
Figure imgf000103_0002
the point of attachment to X9. [0492] EXEMPLARY ASPECT 63. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-62, wherein (Rcap) is independently selected from OH, COOH, or NH2. [0493] EXEMPLARY ASPECT 64. The crosslinked of any preceding exemplary aspects, particularly Exemplary Aspects 1-63, wherein (Rcap) is independently selected from a C1-12 alkyl, C6-12 aryl, or C1-12 alkyl substituted one or more times by C6-12 aryl. [0494] EXEMPLARY ASPECT 65. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-64, wherein (Rcap) is independently selected from a C1-12 haloalkyl, C6-12 haloaryl, C1-12 alkyl substituted one or more times by C6- 12 haloaryl, or C1-12 haloalkyl substituted one or more times by C6-12 haloaryl. [0495] EXEMPLARY ASPECT 66. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-65, wherein the crosslinking is conducted by heating, electron beam, or UV irradiation. [0496] EXEMPLARY ASPECT 67. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-66, wherein the crosslinking is conducted in the absence of a crosslinker. [0497] EXEMPLARY ASPECT 68. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-67, wherein the crosslinking is conducted in the presence of a crosslinker. [0498] EXEMPLARY ASPECT 69. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-68, wherein the crosslinking is conducted in the presence of a crosslinker selected from a C4-30 unsaturated group having at least two carbon-carbon double bonds, a C2-30 group having at least two azide groups, a C2-30 group having at least two amine or thiol groups. [0499] EXEMPLARY ASPECT 70. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-69, wherein the crosslinking is conducted in the presence of a crosslinker comprising diallylmethyl amine, divinylbenze, ethylene glycol diacrylate, polyoxyethylene bis(azide), diethylene glycol bis(azidoacetate), 1,6 diazidohexane, 4,4′-bis(azidomethyl)-1,1′-biphenyl, ethylene glycol diacrylate, poly(ethylene glycol) diacrylate, neopentyl glycol diacrylate, trimethylolpropane triacrylate, pentaerythritol triacrylate, glycerol propoxylate triacrylate, trimethylolpropane propoxylate triacrylate, trimethylolpropane ethoxylate triacrylate, pentaerythritol tetraacrylate, di(trimethylolpropane) tetraacrylate, divinylbenzene, divinyl sulfone, 1,4-butanediol divinyl ether, ethylene glycol divinyl ether, di- tri-, and poly-ethylene glycol divinyl ether, or a combination thereof. [0500] EXEMPLARY ASPECT 71. The crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-70, wherein the crosslinker is present in an amount of 0.01-5 wt.%, 0.1-5 wt.%, 0.5-5 wt.%, 1-5 wt.%, 2.5-5 wt.%, 0.01-1 wt.%, or 0.5-2 wt.%. [0501] EXEMPLARY ASPECT 72. A method of making the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71, comprising preparing a polyurethane by a process comprising the steps: preparing a first mixture comprising a macrodiol and disocyanate to give a first polyurethane, wherein the macrodiol comprises a poly(isobutylene) component; optionally forming a second reaction mixture comprising a chain extender and the first polyurethane to give a second polyurethane; and crosslinking the first polyurethane or second polyurethane. [0502] EXEMPLARY ASPECT 73. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-72, wherein the first reaction mixture comprises a chain extender. [0503] EXEMPLARY ASPECT 74. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-74, wherein the macrodiol has an average molecular weight from 100-100,000 Da, from 100-50,000 Da, from 100-25,000 Da, from 100-10,000 Da, from 100-5,000 Da, from 100-2,500 Da, from 100-1,000 Da, from 100-500 Da, from 250-1,000 Da, from 500-1,000 Da, from 500-1,500 Da, from 1,000-2,000 Da, from 1,000-3,000 Da, from 1,000-5,000 Da, from 1,500-2,500 Da, from 1,500-3,000 Da, from 2,500-5,000 Da, from 2,500-10,000 Da, from 5,000-10,000 Da, from 10,000-25,000 Da, from 10,000-50,000 Da, from 25,000-50,000 Da, from 25,000-75,000 Da, or from 50,000-100,000 Da. [0504] EXEMPLARY ASPECT 75. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-74, wherein the macrodiol comprises a poly(alkenyl) component. [0505] EXEMPLARY ASPECT 76. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-75, wherein the macrodiol comprises poly(1,3-butadiene), poly(2,3-dimethyl-1,3-butadine), or poly(isoprene), preferably poly(isoprene). [0506] EXEMPLARY ASPECT 77. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-76, wherein the macrodiol comprises a poly(isoprene) component. [0507] EXEMPLARY ASPECT 78. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-77, wherein the macrodiol comprises a poly(isobutylene- co-isoprene) random copolymer. [0508] EXEMPLARY ASPECT 79. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-78, wherein the macrodiol comprises a poly(alkynyl) component. [0509] EXEMPLARY ASPECT 80. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-79, wherein the macrodiol comprises a poly(alkyl) component, wherein the poly(alkyl) is not polyisobutylene. [0510] EXEMPLARY ASPECT 81. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-80, wherein the macrodiol comprises a poly(ethylene) component. [0511] EXEMPLARY ASPECT 82. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-81, wherein the macrodiol comprises a poly(isobutylene- co-isoprene) component. [0512] EXEMPLARY ASPECT 83. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-82, wherein the macrodiol comprises a poly(isobutylene- co-ethylene) component. [0513] EXEMPLARY ASPECT 84. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-83, wherein the macrodiol comprises a poly(isobutylene- co-ethylene-co-isoprene) component. [0514] EXEMPLARY ASPECT 85. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-84, wherein the macrodiol comprises a poly(meth)acrylate component. [0515] EXEMPLARY ASPECT 86. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-85, wherein the poly(meth)acrylate component comprises an oligomer derived from methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, sec-butyl (meth)acrylate, isobutyl (meth)acrylate, 2-ethylhexyl (meth)acrylate dodecyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, dodecyl methacrylate, octadecyl (meth)acrylate, glycidyl (meth)acrylate, and combinations thereof. [0516] EXEMPLARY ASPECT 87. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-86, wherein the macrodiol comprises a poly(siloxane) component. [0517] EXEMPLARY ASPECT 88. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-87, wherein the macrodiol comprises a poly(dimethylsiloxane) component. [0518] EXEMPLARY ASPECT 89. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-88, wherein the macrodiol has the formula: HO-[-(A1)d- (A2)e-(A3)f-(A4)g-(A5)h-(A6)peg]-OH, wherein A1 is (isobutylene), and d is 1-10,000; A2 is a C1-20alkenyl, and e is 0-500; A3 is a C1-20alkynyl, and f is 0-500; A4 is a C1-20alkyl, and g is 0- 10,000; A5 is a siloxane, and h is 0-10,000; A6 is a polyethylene glycol, and peg is 0-10,000 wherein d, e, f, g, h, and peg represent the number of monomer units. [0519] EXEMPLARY ASPECT 90. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-89, wherein the macrodiol has the formula: HO-[-(A1)d’- (A2)e’-(A3)f’-(A4)g’-(A5)h’-(A6)peg’]-OH, wherein A1 is (isobutylene), and d' is 1-99; A2 is a C1- 20alkenyl, and e' is 0-99; A3 is a C1-20alkynyl,, and f' is 0-99; A4 is a C1-20alkyl, and g' is 0-99; A5 is a siloxane, and h' is 0-99; A6 is a polyethylene glycol, and peg' is 0-99, wherein d' + e' + f' + g' + h' + peg' = 100; and d', e', f', g', h', and peg' represent the wt.% of each component in the macrodiol. [0520] EXEMPLARY ASPECT 91. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-90, wherein A2 has the ,
Figure imgf000107_0001
.
Figure imgf000107_0002
92. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-91, wherein the macrodiol has the formula: HO- [isobutylenyl]i-[isoprenyl]m-[dimethylsiloxane]o-OH; HO-[isobutylenyl]i-[isoprenyl]m- [ethylenyl]n-[ dimethylsiloxane]o-OH; wherein: i is 1-10,000; n is 1-10,000; m is 1-50; and o is 0-10,000. [0522] EXEMPLARY ASPECT 93. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-92, wherein the macrodiol comprises a polyisobutylene diol and a second diol that does not include a polyisobutylene component. [0523] EXEMPLARY ASPECT 94. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-93, wherein the second diol is a polyethylene diol, a siloxane diol, a polyethylene diol, or a combination thereof. [0524] EXEMPLARY ASPECT 95. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-94, wherein the diisocyanate comprises a compound of Formula (1a): [Formula (1a)], wherein wherein R1* is a saturated C2-30 group. [0525] EXEMPLARY ASPECT 96. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-95, wherein R1* has the
Figure imgf000108_0001
, .
Figure imgf000108_0002
particularly Exemplary Aspects 1-96, wherein the diisocyanate comprises a compound of Formula (2a): [Formula (2a)], wherein R2* is an unsaturated C2-30 group.
Figure imgf000108_0003
[0527] EXEMPLARY ASPECT 98. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-97, wherein R2* groups ,
Figure imgf000108_0004
or emplary aspects, particularly Exemplary Aspects 1-98, wherein the diisocyanate comprises a compound of Formula (3a): [Formula (3a)], wherein R3* is a C6-30 aromatic group. [0529] EXEMPLARY ASPECT 100. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-99, wherein R3* has the ,
Figure imgf000109_0001
.
Figure imgf000109_0002
exemplary aspects, particularly Exemplary Aspects 1-100, wherein the chain extender comprises a compound of Formula (4a): [Formula (4a)], wherein X1 is O or NH; X2 is O or NH; R4* is a C2-30 saturated aliphatic group. [0531] EXEMPLARY ASPECT 102. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-101, wherein R4 has the structure: *-(CH2)4aX4a(CH2)4b-#, wherein * represents the point of attachment to X1 and # represents the point of attachment to X2; X4a is null, CHR4a, C(R4a)2, O, NH, or NCH3; R4a is independently C1-8alkyl; 4a is 0-12; and 4b is 0-12, wherein when X4a is null, O, NH, or NCH3, the sum of 4a and 4b is at least 2, and when X4a is CHR4a, the sum of 4a and 4b is at least 1. [0532] EXEMPLARY ASPECT 103. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-102, wherein X1 is O or NH, X2 is NH, X4a is O, 4a is 2-12, and 4b is 0. [0533] EXEMPLARY ASPECT 104. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-103, wherein 4a is 2-12, X4a is null, and 4b is 0. [0534] EXEMPLARY ASPECT 105. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-104, wherein one of 4a and 4b is 1, and the other of 4a and 4b is 0, and X4a is CHR4a or C(R4a)2. [0535] EXEMPLARY ASPECT 106. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-105, wherein X4a is C(CH3)2. [0536] EXEMPLARY ASPECT 107. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-107, wherein the chain extender comprises a compound of Formula [Formula (5a)], X3 is O or NH; X4 is O or NH; R5* is a C2-30
Figure imgf000110_0001
[0537] EXEMPLARY ASPECT 108. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-107, wherein R5* has the structure: *-(CH2)5aX5a(CH2)5b-#, wherein * represents the point of attachment to X3 and # represents the point of attachment to X4; X5a is CHR5a, C(R5a)2, -CH=CH-, or -C≡C-; R5a is, in each case, independently a C2-12 group, wherein when two of R5a are present, at least one of R5a is an unsaturated C2-12 group; 5a is 0-12; 5b is 0-12, wherein when X5a is CH=CH-, or -C≡C-, then 5a is 1-12, and 5b is 1- 12, and when X5a is CHR5a, the sum of 5a and 5b is at least 1. [0538] EXEMPLARY ASPECT 109. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-108, X3 is O or NH, X4 is NH, X5a is O, and 5b is 0. [0539] EXEMPLARY ASPECT 110. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-109, wherein 5a is 1-12, 5b is 1-12, and X5a is -CH=CH- or -C≡C. [0540] EXEMPLARY ASPECT 111. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-110, one of 5a and 5b is 1, and the other of 5a and 5b is 0, and X5a is CHR5a or C(R5a)2. [0541] EXEMPLARY ASPECT 112. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-111, wherein R5a is C2-4alkenyl. [0542] EXEMPLARY ASPECT 113. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-112, wherein the chain extender comprises a compound of Formula : [Formula (6a)], X6 is O or NH; X7 is O or NH; R6* is a C2-30 aromatic
Figure imgf000111_0001
[0543] EXEMPLARY ASPECT 114. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-113, wherein the chain connector comprises a compound of [Formula (7a)], X8 is O or NH; X9 is O or NH; R7* is an
Figure imgf000111_0002
[0544] EXEMPLARY ASPECT 115. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-114, wherein X8 and X9 are both O, and R7* is an unsaturated C4-10 group having a single unsaturated carbon-carbon bond. [0545] EXEMPLARY ASPECT 116. The method of any preceding exemplary aspects, ,
Figure imgf000111_0003
the point of attachment to X9. [0546] EXEMPLARY ASPECT 117. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-116, wherein the polyurethane is not combined with a chain connector. [0547] EXEMPLARY ASPECT 118. The method of any preceding exemplary aspects, particularly Exemplary Aspects 1-117, wherein the polyurethane is combined with a chain connector in an amount that is from 1-99% relative to polyurethane. [0548] EXEMPLARY ASPECT 119. A medical device comprising the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71. [0549] EXEMPLARY ASPECT 120. The medical device of any preceding exemplary aspects, particularly Exemplary Aspect 119, wherein the medical device is an implantable heart valve. [0550] EXEMPLARY ASPECT 121. The medical device of claim of any preceding exemplary aspects, particularly Exemplary Aspect 120, comprising an annular frame comprising an inflow end and an outflow end and being radially compressible and expandable between a radially compressed configuration and a radially expanded configuration; a leaflet structure comprising one or more leaflets and positioned with the frame and secured thereto; and an inner skirt mounted inside of the frame, and wherein at least one of the one or more leaflets or the inner skirt comprises the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71. [0551] EXEMPLARY ASPECT 122. The medical device of any preceding exemplary aspects, particularly Exemplary Aspect 121, wherein the one or more leaflets comprise the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71. [0552] EXEMPLARY ASPECT 123. The medical device of any preceding exemplary aspects, particularly Exemplary Aspect 121 or 122, wherein the inner skirt comprises the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71. [0553] EXEMPLARY ASPECT 124. The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 122-123, wherein the one or more leaflets exhibit a tensile strength of 20 MPa to 40 MPa. [0554] EXEMPLARY ASPECT 125. The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 122-124, wherein the one or more leaflets exhibit an elastic modulus of 15 MPa to 25 MPa. [0555] EXEMPLARY ASPECT126. The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 122-125, wherein the one or more leaflets exhibit an elongation greater than 300%. [0556] EXEMPLARY ASPECT127. The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 123-126, wherein the inner skirt exhibits a tensile strength of 100 MPa to 200 MPa. [0557] EXEMPLARY ASPECT 128. The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 123-127, wherein the inner skirt exhibits an elastic modulus of 50 MPa to 150 MPa. [0558] EXEMPLARY ASPECT 129. The medical device of any preceding exemplary aspects, particularly Exemplary Aspects 123-128, wherein the inner skirt exhibits an elongation of 100% to 150 %. [0559] EXEMPLARY ASPECT 130. The medical device of any preceding exemplary aspects, particularly Exemplary Aspect 122, wherein the medical device comprises one or more components of electrical simulations system, cardiac system, stents, grafts, scaffolds, catheters, vascular access ports, dialysis ports, dental implants, artificial ligaments, orthopedic prosthesis, or any combination there. [0560] EXEMPLARY ASPECT 131. A film comprising the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71. [0561] EXEMPLARY ASPECT 132. A fiber comprising the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71. [0562] EXEMPLARY ASPECT 133. A yarn comprising one or more fibers of any preceding exemplary aspects, particularly Exemplary Aspect 132. [0563] EXEMPLARY ASPECT 134. A textile comprising one or more yarns of any preceding exemplary aspects, particularly Exemplary Aspect 133. [0564] EXEMPLARY ASPECT 135. The textile of any preceding exemplary aspects, particularly Exemplary Aspect 134, wherein the textile is woven or knitted. [0565] EXEMPLARY ASPECT 136. A coating comprising the crosslinked polyurethane of any preceding exemplary aspects, particularly Exemplary Aspects 1-71. [0566] EXEMPLARY ASPECT 137. A medical device comprising the film of any preceding exemplary aspects, particularly Exemplary Aspect 131. [0567] EXEMPLARY ASPECT 138. A medical device comprising the fiber of any preceding exemplary aspects, particularly Exemplary Aspect 132. [0568] EXEMPLARY ASPECT 139. A medical device comprising the textile of any preceding exemplary aspects, particularly Exemplary Aspects 134 or 135. [0569] EXEMPLARY ASPECT 140. A medical device comprising the coating of any preceding exemplary aspects, particularly Exemplary Aspect 136. [0570] The compositions and methods of the appended claims are not limited in scope by the specific compositions and methods described herein, which are intended as illustrations of a few aspects of the claims, and any compositions and methods that are functionally equivalent are intended to fall within the scope of the claims. Various modifications of the compositions and methods, in addition to those shown and described herein, are intended to fall within the scope of the appended claims. Further, while only certain representative compositions and method steps disclosed herein are specifically described, other combinations of the compositions and method steps also are intended to fall within the scope of the appended claims, even if not specifically recited. Thus, a combination of steps, elements, components, or constituents may be explicitly mentioned herein or less, however, other combinations of steps, elements, components, and constituents are included, even though not explicitly stated. Other than in the examples, or where otherwise noted, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood at the very least and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, to be construed in light of the number of significant digits and ordinary rounding approaches.

Claims

CLAIMS 1. A crosslinked polyurethane, said crosslinked polyurethane obtained by crosslinking a polyurethane having the formula: wherein
Figure imgf000115_0001
a is from 1-10,000; b is from 1-10,000; c is from 0-500; Rcap is a capping group; [soft] represents a macrodiol segment comprising a poly(isobutylene) component; [DI] represents a diisocyante component; [CE] represents a chain extender component; [CC] represents a chain connector component, wherein one or more of [soft], [DI], [CE], and [CC] comprises a crosslinkable group. 2. The crosslinked polyurethane of claim 1, wherein the crosslinkable group comprises a carbon-carbon double bond, carbon-carbon triple bond, epoxide, carboxylic acid, activated carboxylic acids, a clickable group, or combination thereof. 3. The crosslinked polyurethane claim 1, wherein [soft] comprises a polyethylene glycol component. 4. The crosslinked polyurethane of claim 1, wherein [soft] comprises an oligomer having the formula: -[-(A1)d-(A2)e-(A3)f-(A4)g-(A5)h-(A6)peg]-, wherein A1 is (isobutylene), and d is 1-10,000; A2 is C4-20alkenyl, and e is 0-500; A3 is C4-20alkynyl, and f is 0-500; A4 is C2-20alkyl, and g is 0-10,000; A5 is a siloxane, and h is 0-10,000; A6 is a polyethylene glycol, and peg is 0-10,000; and wherein d, e, f, g, h, and peg represent the number of monomer units. 5. The crosslinked polyurethane of claim 4, wherein A4 is ethylene or a mixture of (ethylene) and (propylene), A2 is (1,3-butadiene), (2,3-dimethyl-1,3-butadine), (isoprene), or a combination thereof, and A5 is (dimethyl)siloxane.. 6. The crosslinked polyurethane of claim 4, wherein A3 and A6 are absent. 7. The crosslinked polyurethane of claim 4, wherein [soft] is an oligomer having the formula: -[isobutylenyl]i-[isoprenyl]m-[dimethylsiloxane]o-, or -[isobutylenyl]i-[isoprenyl]m-[ethylenyl]n-[ dimethylsiloxane]o-; wherein: i is 1-10,000; n is 1-10,000; m is 1-50; and o is 0-10,000. 8. The crosslinked polyurethane of claim 1, wherein [DI] includes segments of Formula (1): [Formula (1)],
Figure imgf000116_0001
wherein the wavy lines represent points of attachment to any of [soft], [CE], or [CC], wherein R1 is a saturated C2-30 group. 9. The crosslinked polyurethane of claim 1, wherein [DI] includes segments of Formula (2): [Formula (2)], wherein the wavy
Figure imgf000117_0001
attachment to any of [soft], [CE], or [CC], wherein R2 is an unsaturated C2-30 group. 10. The crosslinked polyurethane of claim 1, wherein [DI] includes segments of Formula (3): [Formula (3)], wherein the wavy
Figure imgf000117_0002
attachment to any of [soft], [CE], or [CC], wherein R3 is a C6-30 aromatic group. 11. The crosslinked polyurethane of claim 1, wherein [CE] includes segments of Formula (4): [Formula (4)],
Figure imgf000117_0003
wherein the wavy lines of attachment to [DI], X1 is O or NH; X2 is O or NH; and R4 is a saturated C2-30 group or R4 has the structure: *-(CH2)4aX4a(CH2)4b-#, wherein * represents the point of attachment to X1 and # represents the point of attachment to X2; X4a is null, CHR4a, C(R4a)2, O, NH, or NCH3; R4a is independently C1-8alkyl; 4a is 0-12; and 4b is 0-12, wherein when X4a is null, O, NH, or NCH3 the sum of 4a and 4b is at least 2, and when X4a is CHR4a or C(R4a)2 the sum of 4a and 4b is at least 1. 12. The crosslinked polyurethane of claim 1, wherein [CE] includes segments of Formula (5): [Formula (5)], wherein the wavy lines
Figure imgf000118_0001
of attachment to [DI], X3 is O or NH; X4 is O or NH; R5 is an unsaturated C2-30 group or R5 has the structure: *-(CH2)5aX5a(CH2)5b-#, wherein * represents the point of attachment to X3 and # represents the point of attachment to X4; X5a is CHR5a, C(R5a)2, -CH=CH-, or -C≡C-, R5a is, in each case, independently a C2-12 group, wherein when two of R5a are present, at least one of R5a is an unsaturated C2-12 group; 5a is 0-12; and 5b is 0-12, wherein when X5a is CH=CH-, or -C≡C-, then 5a is 1-12, and 5b is 1-12, and when X5a is CHR5a, the sum of 5a and 5b is at least 1. 13. The crosslinked polyurethane of claim 1, wherein [CE] includes segments of Formula (6): [Formula (6)], wherein the wavy lines
Figure imgf000119_0001
of attachment to [DI], X6 is O or NH; X7 is O or NH; and R6 is a C6-30 aromatic group. 14. The crosslinked polyurethane of claim 1, wherein [CC] is a segment of Formula (7): [Formula (7)], wherein the wavy lines
Figure imgf000119_0002
of attachment to [DI], X8 is O or NH; X9 is O or NH; and R7 is an unsaturated C2-30 group. 15. The crosslinked polyurethane of any of claims 1-14, wherein the crosslinking is conducted by heating, electron beam, or UV irradiation. 16. The crosslinked polyurethane of any of claims 1-14, wherein the crosslinking is conducted in the absence of a crosslinker. 17. The crosslinked polyurethane of any of claims 1-14, wherein the crosslinking is conducted in the presence of a crosslinker. 18. The crosslinked polyurethane of claim 17, wherein the crosslinking is conducted in the presence of a crosslinker selected from a C4-30 unsaturated group having at least two carbon-carbon double bonds, a C2-30 group having at least two azide groups, a C2-30 group having at least two amine or thiol groups. 19. A method of making the crosslinked polyurethane of any of claims 1-18, comprising preparing a polyurethane by a process comprising the steps: preparing a first mixture comprising a macrodiol and disocyanate to give a first polyurethane, wherein the macrodiol comprises a poly(isobutylene) component; optionally forming a second reaction mixture comprising a chain extender and the first polyurethane to give a second polyurethane; and crosslinking the first polyurethane or second polyurethane. 20. A medical device comprising an annular frame comprising an inflow end and an outflow end and being radially compressible and expandable between a radially compressed configuration and a radially expanded configuration; a leaflet structure comprising one or more leaflets and positioned with the frame and secured thereto; and an inner skirt mounted inside of the frame, and wherein at least one of the one or more leaflets or the inner skirt comprises the crosslinked polyurethane of any one of claims 1-18.
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