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WO2009129221A1 - Composés polyfonctionnels et compositions et procédés de ciment de verre ionomère destinés à être utilisés comme matériaux d'implants - Google Patents

Composés polyfonctionnels et compositions et procédés de ciment de verre ionomère destinés à être utilisés comme matériaux d'implants Download PDF

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WO2009129221A1
WO2009129221A1 PCT/US2009/040482 US2009040482W WO2009129221A1 WO 2009129221 A1 WO2009129221 A1 WO 2009129221A1 US 2009040482 W US2009040482 W US 2009040482W WO 2009129221 A1 WO2009129221 A1 WO 2009129221A1
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polymer
independently selected
arm
cement
acid
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Dong Xie
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Indiana University Research and Technology Corp
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Indiana University Research and Technology Corp
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    • 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
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/12—Ionomer cements, e.g. glass-ionomer cements

Definitions

  • the invention described herein pertains to polyfunctional compounds and glass- ionomer cement compositions.
  • the invention described herein pertains to polyfunctional compounds and glass-ionomer cement compositions and their use in various dental, bone and orthopaedic repair, including augmentation and restoration.
  • GICs are generally water-based dental restoratives that harden following an acid-base reaction between calcium and/or aluminum cations released from a reactive glass and carboxyl anions pendent on polyacids.
  • the success of these cements is attributed to the fact that they have unique and desirable properties such as direct adhesion to tooth structure and base metals (Hotz et al., Br. Dent. J., 142:41-47 (1977); Lacefield et al., J. Prosthet. Dent., 53:194-198 (1985)), antic ariogenic properties due to release of fluoride (Forsten et al., Scand. J.
  • the polymer backbones of GICs are generally prepared from polyacrylic acid homopolymers, poly(acrylic acid-co-itaconic acid) copolymers and/or poly(acrylic acid-co- maleic acid) copolymers (Nicholson, Biomaterials, 19:485-494 (1998)). Even so, despite such advantages of GICs, and similarly for light-cured GICs
  • LCGICs light-cured GICs
  • RGIC resin-modified GIC
  • redox-initiated GICs which have shown improvements in properties such as higher mechanical strength and controllable curing time (Xie et al., Eur. Polym. J., 40:343-351 (2004)).
  • Another strategy is to directly increase molecular weight (MW) of the polyacid by either introducing amino acid derivatives or N-vinylpyrrolidone into the backbone of conventional poly(acrylic acid) homopolymer or poly(acrylic acid-co-itaconic acid) copolymer based GICs, which has been found to improve mechanical and bonding strength (Kao et al.,
  • a lower viscosity of the polyacid backbone in water is often a required feature to ensure such workability to the formulation while also attempting to maintain the mechanical strength.
  • certain GIC systems include tartaric acid to adjust working properties; however, as a low molecular weight molecule, tartaric acid has been observed to correspondingly reduce mechanical strength (Xie et al., Dent. Mater., 21:739-748 (2005)).
  • N- vinyl pyrrolidone has been incorporated into the backbone of poly(acrylic acid-itaconic acid) based GICs for improved working properties; however, the mechanical strength did not show any significant improvement, possibly due to the presence of less carboxylic acid functional groups on the polymer backbone (Xie et al., J. M. S., Pure Appl. Chem., A35:615-1629 (1998)).
  • dental and orthopaedic implants are desirably bioactive (Ratner et al., Biomaterials Science, An Introduction to Materials in Medicine, 2nd Ed, San Diego, CA, Elsevier Academic Press, 2004). Such materials are generally referred to as bioactive GICs or bioactive glass (BAG) containing GICs.
  • bioactive GICs or bioactive glass (BAG) containing GICs.
  • GICs have also been formulated in an attempt to stimulate bone growth (Kamitakahara et al., Biomaterials, 22:3191-3196 (2001)), to replace bone (Brook et al., Biomaterials, 19:565-71 (1998)) and to cap dentin for reduced hypersensitivity (Yli-Urpo et al., Biomaterials, 26:5934- 5941 (2005)).
  • BAG has been incorporated into certain GICs in an attempt to enhance these desired bioactivities (Biomaterials, 26:5934-5941 (2005); Dental Materials, 21:201-209 (2005)).
  • bioactive glass-containing GICs may exhibit bioactivity under simulated physiological conditions and may mineralize human dentin both in vitro and in vivo, it was reported that incorporating BAGs into GICs compromised the mechanical strength of the implant, limiting the utility of the products in dental clinics (Yli-Urpo et al., J. Biomater. Appl., 19:5-20 (2004)).
  • bioactive cement compositions prepared from glass-ionomer compositions.
  • the glass includes a bioactive glass
  • the ionomer composition is a polyfunctional prepolymer that is curable, including light curable polyfunctional prepolymers.
  • Compositions described herein exhibit strength properties that are suitable for preparing implant materials, such as bone and dental implant materials, such as for the repair and/or restoration of bones and teeth.
  • the cement compositions described herein are suitable for use as high load bearing bone and dental implants.
  • compositions that include one or more additional filler components are also described herein are the preparation and use of multifunctional core containing polycarboxylic acids.
  • the multifunctional cores include a plurality of such polycarboxylic acids each connected to the core via sulfur through a sulfide bond.
  • the multifunctional core containing polycarboxylic acids are prepared via a chain- transfer polymerization reaction using an initiating thiol, also referred to as mercaptyl, residue and one or more acrylic acids, such as acrylic acid, methacrylic acid, itaconic acid, and the like.
  • the multifunctional core containing polycarboxylic acids are used for preparing cements for a wide variety of applications, including but not limited to orthopaedic, bone, and dental applications, where the cements are used in the repair and/or restoration of defects in bones and teeth.
  • additional materials such as fillers may also be included.
  • polymers that include polyfunctional core molecules are useful as prostheses or implants in various tissue repair and/or restoration procedures.
  • the monomers used to make such polymers, including those described herein may demonstrate low solution or melt viscosity, thus providing improved workability characteristics.
  • cements may be prepared from such monomers and polymers prepared from the polyfunctional core molecules, and those cements may have improved mechanical strength properties over conventional cements. It has also been discovered that such cements may be mixed with bioactive materials, such as one or more bioactive glasses, and the resulting cement retains or shows improved workability characteristics, and retains or shows improved mechanical strength sufficient for use as implants in high load bearing sites.
  • compositions are described herein for preparing implants.
  • the compositions comprise one or more polymers and/or prepolymer oligomers.
  • the compositions also comprise one or more bioactive glasses.
  • such polymers and prepolymer oligomers include polyfunctional core molecules that may be used to initiate the preparation of a polymer or prepolymer.
  • the polyfunctional core molecules may be used to initiate the preparation of a polymer or prepolymer through a thiol group.
  • polyfunctional core refers to those molecules that have a plurality of functional groups, such as, for example, thiol groups, that may be optionally used to initiate polymer chains, or which may be modified with oligomers or other prepolymers, each of which may be optionally used to initiate polymer chains.
  • initiators are described that are prepared from a polyfunctional core molecule, where each of the functional groups present on the polyfunctional core molecule is covalently attached to another molecule that includes a functional group, such as, for example, a thiol group, capable of participating in a polymerization reaction with a plurality of acrylates.
  • polyfunctional prepolymers are described herein. Such polyfunctional prepolymers are prepared from polymer core initiators by polymerizing a plurality of acrylates to prepare a polyfunctional core polycarboxylic acid.
  • such polyfunctional prepolymers having a plurality of carboxylic acids are further functionalized by adding crosslinkable groups, such as one or more acryloyl substituted groups as amides and/or esters of the polycarboxylic acids.
  • compositions include one or more bioactive glasses.
  • bioactive glasses include materials that are bioinductive, bioconductive, bioerodable, bioresorptive, and/or biodegradable.
  • bioactive glasses include materials that may attract, induce and/or promote the in-growth of tissue, such as bone or dental tissue.
  • bioactive glasses include materials that may provide relief in the repairs involving deep dental cavity capping or bone restorations. Without being bound by theory, it is suggested that the bioactive glass cement systems described herein may facilitate or promote mineralization of calcium phosphate at or in the repair site.
  • cements useful in the repair and/or restoration of tissues are described. Such cements may be prepared directly from the compositions of polyfunctional prepolymers and/or crosslinkable polyfunctional prepolymers. In one variation, the cements may be prepared directly from the compositions of polyfunctional prepolymers and/or crosslinkable polyfunctional prepolymers and the bioactive glasses described herein. In another variation, the cements may be prepared by co-polymerization of one or more co-monomers and the polyfunctional prepolymers and/or crosslinkable polyfunctional prepolymers described herein, either with or without bioactive glasses described herein.
  • the cements may be prepared by adding additional inorganic fillers, such as glasses, ceramics, biological tissues, and the like, to the compositions of polymerizing polyfunctional prepolymers and/or crosslinkable polyfunctional prepolymers, either with or without bioactive glasses described herein, with the optional inclusion of other co-monomers.
  • additional inorganic fillers such as glasses, ceramics, biological tissues, and the like
  • processes for preparing polymer core initiators, polyfunctional prepolymers, and crosslinkable polyfunctional prepolymers are described herein, including polymerization performed using free-radical polymerization technologies such as atom-transfer radical polymerization (ATRP). Additional synthetic details are described by Matyjaszewski, K., Xia, J., "Atom Transfer Radical Polymerization,” Chem. Rev., 101:2921-2990 (2001).
  • processes for preparing polymer core initiators, polyfunctional prepolymers, and crosslinkable polyfunctional prepolymers are described herein, including polymerization performed using sulfur-initiated polymerization technologies.
  • processes for preparing cements and cement compositions are described herein.
  • the cement systems optionally in the presence of one or more co-monomers, are curable by radiation, heat, and/or radical initiation. In one variation, the cement systems are curable with radiation.
  • processes for preparing the polyfunctional core initiators, polyfunctional prepolymers, and implant polymers are described herein.
  • compositions of polyfunctional core initiators, polyfunctional prepolymers, and implant polymers described herein as cements for the repair and/or restoration of tissue are described herein.
  • PAV polymer/water
  • Figure 2 shows CS of FUJI II LC compared to illustrative cements described herein with and without BAG addition:
  • P/L ratio 3.2 or 2.7
  • Filler FUJI II LC or FUJI II LC + BAG.
  • MW of the 6-arm poly(acrylic acid) 15,272 Daltons
  • Filler FUJI II LC or FUJI II LC + BAG
  • Grafting ratio 50%
  • P/L ratio 2.7 or 2.5.
  • PAV ratio 70:30 or 75:25. All specimens were conditioned in simulated body fluid (SBF) at 37 0 C for 24 h.
  • SBF simulated body fluid
  • Figures 4(a) and 4(b) show the conversion and kinetic plot of the 4-arm poly(t- BA) derived from the FT-IR absorbance spectra.
  • Figure 5 shows the yield compressive strength (YCS), ultimate compressive strength (UCS), and modulus (M) of Examples A-C including a polyfunctional core, compared to linear Example D:
  • Each polymer solution was prepared by mixing a PAA with distilled water (1:1, by weight). Specimens were conditioned in distilled water at 37 0 C for 24 h.
  • Figure 6 shows the compressive strength (CS) and diametral tensile strength (DTS) of illustrative cements described herein:
  • Figure 7a shows the CS, DTS, and flexural strength (FS) of two selected illustrative cements described herein compared to FUJI II LC cement.
  • MW of the polymer 18,066
  • Filler FUJI II LC
  • P/L ratio 2.7
  • P/L ratio 3.2.
  • Specimens were conditioned in distilled water at 37 0 C for 24 h.
  • Figure 7b shows the CS, DTS and FS of Example M (EXPGIC) compared to FUJI II, FUJI II LC and VITREMER.
  • Specimens were conditioned in distilled water at 37 0 C for 24 h.
  • Figure 8 shows the CS and DTS of the light-cured GM-crosslinked
  • Figure 9 shows the change in CS for Example M (EXPGIC), FUJI II, FUJI II LC and VITREMER in the course of aging in water.
  • the h, d and w represent hour, day and week, respectively. Specimens were conditioned in distilled water at 37 0 C prior to testing.
  • Figure 10 shows the cell viability comparison after culturing for 3 days with the eluates from selected cements. Eluates were obtained from the 3-day and 7-day incubation at a concentration of 80%.
  • EXPGIC is Example M; NC is the negative control.
  • Figures 1 l(a) and 1 l(b) show cell viability (% survival) vs. cement eluate concentration: (a) Eluates obtained from a 3-day incubation; (b) Eluates obtained from a 7-day incubation. The cells were incubated with the medium containing different concentrations of the eluates at 37°C for 3 days before MTT testing.
  • EXPGIC is Example M; NC is the negative control.
  • polymer core initiators are described herein. Such polymer core initiators may include from 3 to about 12 functional groups for polymerization. In one embodiment, the polymer core initiators may include 3, 4, 5, or 6 functional groups for polymerization. In one embodiment, the polymer core initiators are dendrimeric and may include from about 8 to about 12, or from about 10 to about 12 functional groups for polymerization.
  • the functional groups may be leaving groups or electrophiles such as halo, alkoxy, acyloxy, sulfonyloxy, and the like, nucleophiles such as hydroxy, amino, carboxy, and the like, or radical initiators such as halo, stannyl, and the like.
  • the functional groups may also be nucleophiles such as thiol groups, also referred to as mercaptyl groups.
  • the polymer core initiators are prepared as esters from polyhydroxy compounds and carboxylic acids, including mercapto carboxylic acids.
  • the polyhydroxy compounds are poly(hydroxyalkyl) compounds including, but not limited to, trimethylolpropane (TMP), pentaerythritol (PE), dipentaerythritol (DPE), and the like.
  • the carboxylic acids are omega halo or omega mercapto alkanoic acids, such as chloroacetic acid, 2-bromopropanoic acid, 3- iodopropanoic acid, 2-bromo-2-methylpropanoic acid, mercaptoacetic acid, 2-mercaptopropanoic acid, 3-mercaptopropanoic acid, 2-mercapto-2-methylpropanoic acid, and the like.
  • omega halo or omega mercapto alkanoic acids such as chloroacetic acid, 2-bromopropanoic acid, 3- iodopropanoic acid, 2-bromo-2-methylpropanoic acid, mercaptoacetic acid, 2-mercaptopropanoic acid, 3-mercaptopropanoic acid, 2-mercapto-2-methylpropanoic acid, and the like.
  • the polymer core initiators are compounds of the formulae (Ia):
  • R is hydrogen or an independently selected alkyl group
  • a is an independently selected integer from 1 to about 4
  • b is an independently selected integer from 1 to about 4
  • X is an independently selected leaving group, such as halo, acyloxy, sulfonyloxy, and the like.
  • the polymer core initiators described herein are compounds of formulae (Ia) where a and b are each independently selected from 1 and 2.
  • the polymer core initiators described herein are compounds of formulae (Ia) where R is in each case independently selected from hydrogen or lower alkyl, such as methyl, ethyl, and the like.
  • the polymer core initiators described herein are compounds of formulae (Ia) where X is halo.
  • the polymer core initiators are compounds of the formulae (Ib):
  • R is hydrogen or an independently selected alkyl group; a is an independently selected integer from 1 to about 4; and b is an independently selected integer from 1 to about 4.
  • polymer core initiators described herein are compounds of formulae (Ib) where a and b are each independently selected from 1 and 2.
  • polymer core initiators described herein are compounds of formulae (Ib) where R is in each case independently selected from hydrogen or lower alkyl, such as methyl, ethyl, and the like.
  • polycarboxylic acids being used in current dental GICs are linear polymers and synthesized via conventional free radical polymerization. It is appreciated that one of the main reasons that different architectures of the polyacids for GIC applications have not been reported may be attributed to the fact that it is difficult to synthesize the polymers with different architectures by using conventional free-radical polymerization techniques.
  • Atom-transfer radical polymerization is capable of making various architectures such as star polymers and block copolymers.
  • polyfunctional core molecules are described herein.
  • the polyfunctional prepolymers are polymer core initiators further functionalized with polycarboxylic acids, such as poly(acrylic acid)s (PAA)s, and derivatives thereof.
  • PAA poly(acrylic acid)s
  • PAAs include, but are not limited to, homo and co-polymers of acrylic acid, methacrylic acid, crotonic acid, maleic acid, fumaric acid, itaconic acid, citraconic acid, mesaconic acid, and the like.
  • acrylic acid starting materials that are used to prepare the PAAs described herein may be esters, amides, or acid salts.
  • acrylic acid starting materials include methyl esters, ethyl esters, tert-butyl esters and the like.
  • acrylic acid starting materials include amides, alkylamides, dialkylamides, dipeptides, and the like.
  • acrylic acid starting materials include monovalent and polyvalent cationic salts such as lithium, sodium, potassium, cesium, calcium, magnesium, and the like.
  • polymer and copolymer such as referring to polycarboxylic acid Q may refer both individually and collectively to statistically distributed polymers, random polymers, grafting co-polymers, macromers, comb polymers, and block copolymers.
  • the polymer or copolymer included in the polyfunctional prepolymers described herein is a graft polymer.
  • the polymer or copolymer included in the polyfunctional prepolymers described herein is a comb polymer.
  • the polymer or copolymer included in the polyfunctional prepolymers described herein is a random polymer.
  • the polyfunctional prepolymer is a compound of the formulae (Ha):
  • R is hydrogen or an independently selected alkyl group
  • a is an independently selected integer from 1 to about 4
  • b is an independently selected integer from 1 to about 4
  • Q is an independently selected polymer, which may be a statistically distributed polymer, a random polymer, a grafting co-polymer, block copolymer, and the like, of one or more acrylic acids, or ester, amide, or salt derivatives thereof
  • Y is an independently selected leaving group, such as halo, acyloxy, sulfonyloxy, and the like.
  • each branch of the compounds of formula (Ha) illustratively has a number average molecular weight in the range from about 750 to about 50,000, or in the range from about 750 to about 25,000. In another embodiment, each branch of the compounds of formula (Ha) illustratively has a weight average molecular weight in the range from about 900 to about 120,000.
  • the polyfunctional prepolymers described herein are compounds of formulae (Ha) where a and b are each independently selected from 1 and 2.
  • the polyfunctional prepolymers described herein are compounds of formulae (Ha) where R is in each case independently selected from hydrogen or lower alkyl, such as C1-C4 alkyl, methyl, ethyl, and the like.
  • the polyfunctional prepolymer described herein are compounds of formulae (Ha) where Y is halo.
  • the polyfunctional prepolymer described herein are compounds of formulae (Ha) where Q is a homopolymer or copolymer of acrylic acid, methacrylic acid, maleic acid, and/or itaconic acid, or one or more carboxylic acid derivatives thereof.
  • the polyfunctional prepolymer described herein are compounds of formulae (Ha) where Q is a homopolymer or copolymer of acrylic acid and/or methacrylic acid, or one or more carboxylic acid derivatives thereof.
  • Q is a homopolymer or copolymer of acrylic acid and/or methacrylic acid amides.
  • Q is a homopolymer or copolymer of acrylic acid and/or methacrylic acid esters.
  • the polyfunctional prepolymer is a compound of the formulae (lib):
  • R is hydrogen or an independently selected alkyl group
  • a is an independently selected integer from 1 to about 4
  • b is an independently selected integer from 1 to about 4
  • Q is an independently selected polycarboxylic acid, said carboxylic acids selected from the group consisting of acrylic acids, and ester, amide, and salt derivatives thereof.
  • each branch of the compounds of formula (lib) illustratively has a number average molecular weight in the range from about 500 to about 100,000, or in the range from about 500 to about 50,000. In another embodiment, each branch of the compounds of formula (lib) illustratively has a weight average molecular weight in the range from about 750 to about 150,000.
  • the polyfunctional prepolymers described herein are compounds of formulae (lib) where a and b are each independently selected from 1 and 2.
  • the polyfunctional prepolymers described herein are compounds of formulae (lib) where R is in each case independently selected from hydrogen or lower alkyl, such as C1-C4 alkyl, methyl, ethyl, and the like.
  • the polyfunctional prepolymer described herein are compounds of formulae (Ha) where Q is a homopolymer or copolymer of acrylic acid, methacrylic acid, maleic acid, and/or itaconic acid, or one or more carboxylic acid derivatives thereof.
  • the polyfunctional prepolymer described herein are compounds of formulae (lib) where Q is a homopolymer or copolymer of acrylic acid and/or methacrylic acid, or one or more carboxylic acid derivatives thereof.
  • Q is a homopolymer or copolymer of acrylic acid and/or methacrylic acid amides.
  • Q is a homopolymer or copolymer of acrylic acid and/or methacrylic acid esters.
  • crosslinkable polyfunctional prepolymers are described herein.
  • the crosslinkable polyfunctional prepolymers are polyfunctional prepolymers further functionalized as acryloyloxy substituted alkyl esters or acryloyloxy substituted alkyl amides.
  • the crosslinkable polyfunctional prepolymers are polyfunctional prepolymers further functionalized as acryloylamino substituted alkyl esters or acryloylamino substituted alkyl amides.
  • acryloyl is understood to refer to substituted and unsubstituted acryloyls.
  • acryloyls include, but are not limited to, acryloyl, methacryloyl, crotonoyl, maleoyl, fumaroyl, itaconoyl, citraconoyl, mesaconoyl, and the like.
  • the acryloyl is curable with radiation.
  • the acryloyl is curable under radical conditions, such as in the presence of heat and/or a radical initiator.
  • the acryloyl is a methacryloyl.
  • substituted alkyl esters or substituted alkyl amides crosslinkable to the polyfunctional prepolymers are prepared from acryloyloxy and acryloylamino alkylisocyanates, alkylepoxides, alkanols, alkylcarboxylic acids, and derivatives thereof, and the like.
  • crosslinkable groups may also include solubilizing groups, such as water solubilizing groups.
  • solubilizing groups such as water solubilizing groups.
  • HEMA solubilizing monomers
  • other monomers such as HEMA, and the like may be optionally added.
  • crosslinkable polyfunctional prepolymer is a compound of the formulae (Ilia):
  • R is hydrogen or an independently selected alkyl group
  • a is an independently selected integer from 1 to about 4
  • b is an independently selected integer from 1 to about 4
  • Q a is an independently selected polymer, which may be a statistically distributed polymer, a random polymer, a grafting co-polymer, block copolymer, and the like, of one or more acrylic acids, or ester, amide, or salt derivatives thereof
  • Y is an independently selected leaving group; providing that at least a portion of the acrylic acids forming the polymer Q a includes one or more esters and/or amides of alcohols and/or amines each independently selected from the group consisting of acryloyloxyalkanols, acryloyloxyalkylamines, acryloylaminoalkanols, and acryloylaminoalkylamines, each of which is optionally substituted, such as with alkyl, hydroxy, halo, carboxyl, and
  • the crosslinking polyfunctional prepolymers described herein are compounds of formulae (Ilia) where a and b are each independently selected from 1 and 2.
  • the polyfunctional prepolymer described herein are compounds of formulae (Ilia) where R is in each case independently selected from hydrogen or lower alkyl, such as methyl, ethyl, and the like.
  • the polyfunctional prepolymer described herein are compounds of formulae (Ilia) where Y is halo.
  • the polyfunctional prepolymer described herein are compounds of formulae (Ilia) where Q a is a homopolymer or copolymer of acrylic acid, methacrylic acid, maleic acid, and/or itaconic acid, or one or more carboxylic acid derivatives thereof.
  • the polyfunctional prepolymer described herein are compounds of formulae (Ilia) where Q a is a homopolymer or copolymer of acrylic acid and/or methacrylic acid, or one or more carboxylic acid derivatives thereof.
  • Q a is a homopolymer or copolymer of one or more acrylic acids, acrylic acid amides, methacrylic acids, and/or methacrylic acid amides.
  • Q a is a homopolymer or copolymer of one or more acrylic acids, acrylic acid esters, methacrylic acids, and/or methacrylic acid esters.
  • Q a includes a plurality of acryloyloxyalkanols as esters, such as esters of acryloyl and/or methacryloyl ethylene glycols.
  • Q a includes a plurality of acryloyloxyalkanols as esters, such as esters of acryloyl and/or methacryloyl glycerols.
  • Q a includes a plurality of acryloyloxyalkylamines as amides, such as amides of acryloyl and/or methacryloyl hydroxy ethylamines.
  • Q a includes a plurality of acryloylaminoalkylamines as amides, such as amides of acryloyl and/or methacryloyl ethylenediamines.
  • the light-curable polyfunctional prepolymer is a compound of the formula:
  • Q a is wherein x and y are each independently selected in each instance from an integer in the range from O to about 5, and n is an integer independently selected in each instance in the range from 1 to about 1000.
  • x and y are each an independently selected integer in the range from 1 to about 4.
  • x, y, and n are each an independently selected integer in the range from 1 to about 4.
  • X is NH-CH 2 -CH 2 -O (IEM).
  • X is 0-CH 2 -CH(OH)-CH 2 -O (GM).
  • the portion of the acrylic acids forming the polymer Q a that comprises esters or amides, or combinations thereof, of an alcohol or amine each independently selected from the group consisting of acryloyloxyalkanols, acryloyloxyalkylamines, acryloylaminoalkanols, and acryloylaminoalkylamines, each of which is optionally substituted, is about 5% to about 90%, about 20% to about 75%, or about 35% to about 60%.
  • crosslinkable polyfunctional prepolymer is a compound of the formulae (HIb):
  • R is hydrogen or an independently selected alkyl group
  • a is an independently selected integer from 1 to about 4
  • b is an independently selected integer from 1 to about 4
  • Q is an independently selected polycarboxylic acid, said carboxylic acids selected from the group consisting of acrylic acids, and ester, amide, and salt derivatives thereof; providing that at least a portion of said polycarboxylic acid forming the polymer Q a comprises esters or amides, or combinations thereof, of an alcohol or amine each independently selected from the group consisting of acryloyloxyalkanols, acryloyloxyalkylamines, acryloylaminoalkanols, and acryloylaminoalkylamines, each of which is optionally substituted.
  • the crosslinking polyfunctional prepolymers described herein are compounds of formulae (HIb) where a and b are each independently selected from 1 and 2.
  • the polyfunctional prepolymer described herein are compounds of formulae (HIb) where R is in each case independently selected from hydrogen or lower alkyl, such as methyl, ethyl, and the like.
  • the polyfunctional prepolymer described herein are compounds of formulae (HIb) where Q a is a homopolymer or copolymer of acrylic acid, methacrylic acid, maleic acid, and/or itaconic acid, or one or more carboxylic acid derivatives thereof.
  • the polyfunctional prepolymer described herein are compounds of formulae (HIb) where Q a is a homopolymer or copolymer of acrylic acid and/or methacrylic acid, or one or more carboxylic acid derivatives thereof.
  • Q a is a homopolymer or copolymer of one or more acrylic acids, acrylic acid amides, methacrylic acids, and/or methacrylic acid amides.
  • Q a is a homopolymer or copolymer of one or more acrylic acids, acrylic acid esters, methacrylic acids, and/or methacrylic acid esters.
  • Q a includes a plurality of acryloyloxyalkanols as esters, such as esters of acryloyl and/or methacryloyl ethylene glycols. In another variation, Q a includes a plurality of acryloyloxyalkanols as esters, such as esters of acryloyl and/or methacryloyl glycerols. In another variation, Q a includes a plurality of acryloyloxyalkylamines as amides, such as amides of acryloyl and/or methacryloyl hydroxyethylamines. In another variation, Q a includes a plurality of acryloylaminoalkylamines as amides, such as amides of acryloyl and/or methacryloyl ethylenediamines .
  • the portion of the acrylic acids forming the polymer Q a that comprises esters or amides, or combinations thereof, of an alcohol or amine each independently selected from the group consisting of acryloyloxyalkanols, acryloyloxyalkylamines, acryloylaminoalkanols, and acryloylaminoalkylamines, each of which is optionally substituted, is about 5% to about 90%, about 20% to about 75%, or about 35% to about 60%.
  • the portion of the acrylic acids forming the polymer Q that comprises esters or amides, or combinations thereof, of an alcohol or amine each independently selected from the group consisting of acryloyloxyalkanols, acryloyloxyalkylamines, acryloylaminoalkanols, and acryloylaminoalkylamines, each of which is optionally substituted, is about 5% to about 90%, about 20% to about 75%, or about 35% to about 60%.
  • the light-curable polyfunctional prepolymer is a compound of the formula:
  • a, b, c, d, and e are each independently selected in each instance from an integer in the range from 0 to about 5, and n is an integer independently selected in each instance in the range from 1 to about 1000.
  • a, b, c, d, and e are each an independently selected integer in the range from 1 to about 4.
  • a, b, c, d, e, and n are each an independently selected integer in the range from 1 to about 4.
  • X is NH-CH 2 -CH 2 -O (IEM).
  • X is 0-CH 2 -CH(OH)-CH 2 -O (GM).
  • the crosslinkable prepolymer has a lower viscosity, such as when measured in water, than a conventional cement composition.
  • the crosslinkable prepolymer has a lower viscosity to molecular weight ratio than a conventional cement composition.
  • lower viscosity properties may improve the workability characteristics of cement compositions and cement systems prepared from such crosslinkable prepolymers.
  • such lower viscosity to molecular weight properties may provide cured cements that have higher strength properties, such as higher compressive strength, as compared to conventional cements with similar molecular weights.
  • polymer and copolymer such as referring to polycarboxylic acid Q or crosslinkable polycarboxylic acid Q a , may refer both individually and collectively to statistically distributed polymers, random polymers, grafting co-polymers, macromers, comb polymers, and block copolymers.
  • the polymer or copolymer included in the polyfunctional prepolymers described herein is a graft polymer.
  • the polymer or copolymer included in the polyfunctional prepolymers described herein is a comb polymer.
  • the polymer or copolymer included in the polyfunctional prepolymers described herein is a random polymer.
  • the polymer or copolymer Q or Q a included in the polyfunctional prepolymers described herein is of the formula: where AA 1 and AA 2 are illustrative acrylic acids, such as acrylic acid, methacrylic acid, itaconic acid, and the like, or illustrative crosslinkable acrylic acids, such as the foregoing further derivatized as amides and/or esters of acryloyloxyalkanols, acryloyloxyalkylamines, acryloylaminoalkanols, and acryloylaminoalkylamines, each of which is optionally substituted; and x, y, and z are each independently selected in each instance from integers in the range from 0 to about 3000.
  • the polymer or copolymer Q or Q a included in the polyfunctional prepolymers described herein is of the formula: where x and y are in each instance independently selected integers in the range from 0 to about 5, and z is about 1000. It is to be understood that the above formulae include various combinations of polymer fragments. For example, the following formulae
  • acrylic acids and/or crosslinkable acrylic acids such as AA 3 , AA 4 , and the like may be included in the above formula to prepare the corresponding copolymers of three, four, and the like acrylic acids and/or crosslinkable acrylic acids.
  • a novel glass-ionomer cement system composed of multi- arm poly(carboxylic acid)s is described.
  • these polyacids are synthesized via a chain-transfer polymerization reaction using newly synthesized multi-arm chain-transfer agents.
  • the cements formulated with the multi-arm polyacids described herein show significantly lower viscosities in water as compared to those formulated with their linear counterparts. It is appreciated that, due to the lower viscosities, the MW of the polyacids can be significantly increased for enhanced mechanical strengths while maintaining the ease of mixing and handling.
  • the experimental cements show significantly improved compressive strengths as compared to FUJI II after aging in water for 3 months.
  • the polyfunctional prepolymers are polycarboxylic acids.
  • the processes described herein may be performed on carboxylic acid monomers without the need for any protection of the free carboxylic acid groups.
  • the processes described herein include a thiol, also referred to as mercaptyl, chain transfer agent.
  • the chain transfer agent is included in the polyfunctional core molecule and is used to build the subsequent polycarboxylic acid chain to prepare polyfunctional prepolymers described herein.
  • the polyfunctional prepolymers are compounds such as those described in co-filed and copending United States provisional patent application, titled "Bioactive light- curable glass-ionomer cements for dental and orthopaedic treatment," which is incorporated herein in its entirety by reference.
  • the polyfunctional prepolymers are compounds such as those described in PCT international application publication WO 2007/103665, the disclosure of which is incorporated herein in its entirety by reference.
  • each of the crosslinkable polyfunctional prepolymers described herein, or a combination thereof is combined with a bioactive glass to prepare a bioactive cement system.
  • the bioactive cement system is useful in dental applications, such as in repair and restoration.
  • the dental application includes use in treating high load bearing cavities, including Type I and Type II cavities.
  • the dental application includes root surface fillings.
  • the BAG is present in the cement systems herein in the range from about 10% to about 70% by weight.
  • the BAG used herein may be selected from any of a number of known or conventional materials, including but not limited to bioactive glass S53P4, 45S5, 58S, S70C30, and the like.
  • bioactive glass S53P4 which is composed of SiO 2 , Na 2 O, CaO and P 2 O 5 , can be used for bone and dentin mineralization. It has been reported that the use of S53P4 in combination with conventional, such as linear, glass-ionomer cements for potential dentin mineralization results in materials that exhibit insufficient compressive strength and hardness values to be clinically acceptable (Yli-Urpo et al., Biomaterials, 26:5934- 5941 (2005); Yli-Urpo et al., Dent. Mater., 21:201-9 (2005)).
  • the reason for the low strength and hardness values of such cements may be the lack of formation of any or a sufficient number of chemical interactions or bonds between S53P4 and the GIC. Such a dearth or absence of chemical interactions or bonds may lead to a quick release of the bioactive glass, which is followed by a significant reduction in strength.
  • the cement systems described herein may provide substantially higher mechanical strengths and hardness, and show a significant increase in strength during aging, as compared to commercial cements such as FUJI II LC.
  • a bioactive cement system is described that also includes a filler compounds, such as but not limited to FUJI II LC filler.
  • a bioactive cement system that also includes water.
  • the bioactive cement systems exhibit high mechanical strength and in vitro and/or in vivo bioactivity.
  • the cement systems described herein induce or promote calcium phosphate or hydroxyapatite formation in simulated body fluid.
  • the cement systems described herein induce or promote the mineralization of bone or dentin, and the like.
  • Such systems are generated, for example, by initially determining and optimizing liquid formulations that contain the polymer and water and that may provide desirable compressive strength and diametral tensile strength, then mixing BAG with fillers and incorporating the mixed fillers into the optimal liquid formulations to provide cements having high strength and hardness characteristics.
  • such superior strength characteristics of the GIC systems herein may be attributable to the high content of carboxyl groups, high content of poly(acrylic acids), and/or high MW of poly(acrylic acid).
  • Both high content of poly(acrylic acid) and carboxyl group may help build salt bridges between the metals, such as calcium, in BAGs and carboxyl groups pendent on the polycarboxylic acids.
  • FUJI II LC contains a substantial amount of hydroxyethylmethacrylate (HEMA) and dimethacrylate/oligomethacrylate which are unable to contribute to salt bridge formation, and thus the BAG may be released faster, resulting in a significant reduction in compressive strength.
  • HEMA hydroxyethylmethacrylate
  • dimethacrylate/oligomethacrylate dimethacrylate/oligomethacrylate
  • the BAG-containing cements herein exhibit higher values for yield strength (YS), modulus, ultimate compressive strength (UCS), diametral tensile strength (DTS) and Knoop hardness number (KNH) than those of BAG-containing commercial cements such as FUJI II LC cement.
  • the cement systems herein exhibit an increase in CS upon aging.
  • the cement systems herein exhibit the effect of inducing mineralization of, for example, dentin surfaces upon aging.
  • the co-monomer is a hydroxy, amino, and/or carboxylic acid substituted alkyl amide or ester of an acrylate.
  • acrylate is understood to refer to substituted and unsubstituted acrylates.
  • acrylates include, but are not limited to, acrylate, methacrylate, crotonate, maleate, fumarate, itaconate, citraconate, mesaconate, and the like.
  • such co-monomers are optionally added to polyfunctional prepolymers and/or crosslinkable polyfunctional prepolymers during curing to prepare polymers. It is appreciated that the addition of one or more co-monomers may increase the water solubility, hydrophilicity, and/or solvation of the polymers prepared from polyfunctional prepolymers and/or crosslinkable polyfunctional prepolymers. In addition, it is further appreciated that the addition of one or more co-monomers may increase the homogeneity of composites prepared from polyfunctional prepolymers and/or crosslinkable polyfunctional prepolymers, and fillers, such as glasses, ceramics, other inorganic materials, and the like.
  • the co-monomer is curable with radiation.
  • the co-monomer is curable under radical conditions, such as in the presence of heat and/or a radical initiator.
  • the co-monomer is a hydroxyalkyl ester of methacrylate, or a carboxylalkylamide of methacrylate.
  • GICs prepared from polyfunctional prepolymers and/or crosslinking polyfunctional prepolymers that do not include added co-monomers are described herein. It is appreciated that light-cured RMGICs described herein may have certain advantageous chemical and mechanical features, such as reduced moisture sensitivity, improved mechanical strengths, extended working time, ease of clinical handling, and the like. The advantages of such chemical and mechanical features are described by D. C. Smith,
  • RMGICs may generally be less biocompatible than conventional GICs, as described by C. A. de Souza Costa, J. Hebling, F. Garcia-Godoy, and C. T. Hanks, "In vitro cytotoxicity of five glass-ionomer cements," Biomaterials, 24:3853-3858 (2003); G. Leyhausen, M. Abtahi, M.
  • HEMA 2-hydroxyethyl methacrylate
  • RMGICs require low MW amphiphilic molecules like HEMA. Accordingly, described herein are polyfunctional prepolymers crosslinkable to amphiphilic methacrylate functionalities. It is further suggested that such crosslinking onto the polyfunctional prepolymers may substitute for the HEMA-based hydrophobic methacrylate moieties incorporated into conventional RMGICs.
  • Syntheses of polymer core initiators are also described herein. Also described herein are syntheses of polyfunctional prepolymers. Also described herein are syntheses of crosslinkable polyfunctional prepolymers. In one embodiment, the crosslinkable polyfunctional prepolymers described herein may be prepared using a radical initiated polymerization process. Even so, it is understood that in certain configurations, conventional radical initiated polymerization to prepare polyfunctional prepolymers may be difficult to achieve. Accordingly, in one variation described herein are alternate syntheses of such compounds using atom-transfer radical polymerization (ATRP) processes and techniques. In another embodiment, 4-arm PAA polyfunctional prepolymers are synthesized using ATRP.
  • ATRP atom-transfer radical polymerization
  • the 4-arm PAAs may also be modified by the addition of crosslinkable groups such as one or more of various substituted acrylate and methacrylate esters, such as 2- isocyanatoethyl methacrylate (IEM), glycidyl methacrylate (GM), 2-hydroxyethyl acrylate (HEA), 2-hydroxyethyl methacrylate (HEMA), and the like.
  • crosslinkable groups such as one or more of various substituted acrylate and methacrylate esters, such as 2- isocyanatoethyl methacrylate (IEM), glycidyl methacrylate (GM), 2-hydroxyethyl acrylate (HEA), 2-hydroxyethyl methacrylate (HEMA), and the like.
  • the polyfunctional prepolymers and crosslinkable polyfunctional prepolymers described herein may also be formulated with co- monomers such as HEMA, in addition to water, and various optional polymerization initiators. In one variation, the polymerization of the poly
  • the polymerization of the polyfunctional prepolymers and crosslinkable polyfunctional prepolymers, with the optional addition of one or more co-monomers is performed in the presence of one or more ceramic or glass fillers, including but not limited to various forms of hydroxyapatite, commercially available ceramics, including FUJI II LC filler, and the like.
  • GICs Light-cured, self-cured, and radical cured glass-ionomer cements
  • the GIC is prepared from one or more polyfunctional prepolymers.
  • the GIC is prepared from one or more crosslinkable polyfunctional prepolymers.
  • the GIC is prepared from one or more polyfunctional prepolymers and one or more crosslinkable polyfunctional prepolymers.
  • the GIC is prepared as described herein in the presence of one or more co- monomers.
  • the GIC is prepared from one or more crosslinkable polyfunctional prepolymers and one or more co-monomers.
  • GIC is prepared from one or more crosslinkable polyfunctional prepolymers in the absence of any added co-monomers.
  • GICs are described herein that exhibit improved mechanical properties, illustratively improved mechanical strengths.
  • the cements described herein are evaluated for their mechanical properties.
  • Mechanical properties include various mechanical strength parameters, including but not limited to compressive strength (CS), tensile strength (TS), toughness, modulus (M), and the like.
  • polyfunctional prepolymers, crosslinkable polyfunctional prepolymers, and cements described herein may exhibit improved physical properties, workability properties, and mechanical properties than conventional prepolymers and cements.
  • polyfunctional prepolymers and/or crosslinkable polyfunctional prepolymers described herein have a lower viscosity as compared to the corresponding linear counterpart, or conventional prepolymer.
  • the polyfunctional prepolymers and/or crosslinkable polyfunctional prepolymers described herein have a lower viscosity to molecular weight ratio as compared to the corresponding linear counterpart, or conventional prepolymer.
  • cements prepared from polyfunctional prepolymers and/or crosslinkable polyfunctional prepolymers described herein show higher mechanical strengths than corresponding conventional cements.
  • cements (LCGICs) prepared from both IEM-crosslinked PAAs and GM-crosslinked 4-arm PAAs show higher mechanical strengths than the cements prepared from the corresponding linear prepolymers.
  • the cements prepared from IEM-crosslinked PAAs may show higher CS and DTS than the corresponding cements prepared from GM-crosslinked PAAs.
  • the IEM-crosslinked cements may show higher mechanical strengths than corresponding GM-crosslinked cements, possibly due to a hydrophobicity difference between the two corresponding polymers.
  • the effects of grafting ratio, polymer/water (PAV) ratio, filler powder/polymer liquid (P/L) ratio, and aging on strengths are described for LCGICs prepared from polyfunctional prepolymers and/or crosslinkable polyfunctional prepolymers that are not polymerized or cured with any co-monomer.
  • the 4-arm PAA polymer may exhibit a lower viscosity compared to the corresponding linear counterpart synthesized via conventional free-radical polymerization.
  • increasing PAV ratio may increase both CS and DTS; increasing grafting ratio may increase CS; and increasing P/L ratio may increase CS.
  • kits are described herein.
  • the kit may include one or more polyfunctional prepolymers and/or one or more crosslinkable polyfunctional prepolymers.
  • the kit may also include other formulating materials, including but not limited to co-monomers, initiators, and fillers.
  • the kit may also include a container adapted for mixing the various components of the cement prior to application, implantation, or introduction into the treatment site.
  • the kit also includes instructions for preparing the cement system from the various components, and optionally instructions for application, implantation, or introduction into the treatment site.
  • the polyfunctional prepolymers, crosslinkable polyfunctional prepolymers, and cements described herein may be used as replacement materials for conventional GICs.
  • a curable composition including one or more of the polyfunctional prepolymers and/or one or more crosslinkable polyfunctional prepolymers is placed in the defect, and cured. Curing may take place by initiating with radiation, and/or a chemical reagent, such as a radical initiator.
  • the polyfunctional prepolymers, crosslinkable polyfunctional prepolymers, and cements described herein may also be used in conjunction with other prosthetic materials in the repair or restoration of the tissue.
  • TMP Trimethylolpropane
  • PE pentaerythritol
  • TPA triethylamine
  • DPA dipentaerythritol
  • mercaptoacetic acid 2-mercaptoethanol
  • p-toluenesulfonic acid monohydrate sodium bicarbonate (NaHCO 3 ), sodium chloride (NaCl), acrylic acid (AA), itaconic acid (IA), 2-bromoisobutyryl bromide (BIBB), cuprous bromide (CuBr), N,N,N',N',N"- pentamethyldiethylenetriamine (PMDETA), dl-camphoroquinone (CQ), diphenyliodonium chloride (DC), 2,2'-azobisisobutyronitrile (AIBN), 4,4'-azobis(4-cyanovaleric acid) (ACVA), dibutyltin dilaurate (DBTL), triphenylstilbine (TPS), pyr
  • the MW of the 6-arm poly(acrylic acid) 15,272 Daltons.
  • the water used herein was distilled and deionized.
  • the simulated body fluid (SBF) was prepared following published protocols (Kamitakahara et al., Biomaterials, 22:3191-3196 (2001); Forsback et al., Acta Odontol. Scand., 62:14-20 (2004)).
  • EXAMPLE 2 Formulation and Preparation of Specimens. Synthesis and characterization of the light-curable 6-arm star-shape poly(acrylic acid) polymer was done as described in the literature (Xie et al., Dent. Mater., 23:395-403 (2007)). The cements were formulated with a two-component system (liquid and powder). The liquid was formulated with the light-curable 6-arm star shape poly(acrylic acid), water, 0.9% camphorquinone (CQ, photo- initiator, by weight), 1.8% diphenyliodonium chloride (DC, activator) and 0.05% hydroquinone (HQ, stabilizer). The polymer/water ratios (by weight) are shown in Table 1.
  • CQ camphorquinone
  • DC diphenyliodonium chloride
  • HQ hydroquinone
  • FUJI II LC glass powder was either used alone or mixed with BAG to formulate the cements.
  • the BAG fillers were mixed into FUJI II LC powders in three ratios (by weight): 10%, 15% and 20%.
  • the detailed formulations are shown in Table 1.
  • the cylindrical specimens were prepared in glass tubing with dimensions of 4 mm in diameter by 8 mm in length for compressive strength (CS) and 4 mm in diameter by 2 mm in length for diametral tensile strength (DTS) tests.
  • the disk specimens with dimensions of 4 mm in diameter by 2 mm in thickness were prepared in glass ring covered with transparent plastic sheets on both sides for hardness test. All the specimens were exposed to blue light (EXAKT 520 Blue Light Polymerization Unit, 9W/71, GmbH, Germany) for 1 min, then were conditioned in 100% humidity for 15 min, removed from the mold and conditioned in SBF at 37 0 C for 24 h prior to testing, unless specified.
  • EXAKT 520 Blue Light Polymerization Unit 9W/71, GmbH, Germany
  • EXAMPLE 3 Dentin Disk and Bonding Preparation. Extracted human third molars were cleaned with hand instruments to remove the soft tissue. Each tooth was cut along its horizontal axis just below the dentin-enamel junction using a water-cooled low speed diamond saw. The 1-mm-thick disk prepared from each tooth was cleaned with 0.5% NaOCl at room temperature for 5 min, followed by washing with distilled and deionized water and 70% ethanol for 20 min. The prepared dentin disk was either immersed with one cured cylindrical GIC specimen in SBF or directly bonded to one cylindrical GIC specimen (Lucas et al., Biomaterials, 24:3787-3794 (2003)) followed by immersion in SBF, prior to testing or examination.
  • EXAMPLE 4 Strength Measurements. Strength measurement testing of specimens was performed on a screw-driven mechanical tester (QTest QT/10, MTS Systems
  • EXAMPLE 5 Scanning Electron Microscopic (SEM) Analysis. The surface of the dentin specimen from selected groups was observed over a magnification of 150Ox with a scanning electron microscope (Model XL-30CP, Philips Electronics N.V., The Netherlands) to examine in vitro mineralizations. The specimens were vacuum sputter-coated with gold- palladium (Au-Pd), and a vacuum was used for dehydration of the coated specimens before SEM analysis.
  • SEM Scanning Electron Microscopic
  • EXAMPLE 7 Evaluation of Mechanical Strengths of the Cements.
  • Figure 1 shows the effect of polymer/water (PAV) ratio (by weight) on CS and DTS, after the cements were conditioned in SBF for 24h.
  • FUJI II LC glass fillers without BAG were mixed with the star-shape polymer liquid at different PAV ratios.
  • the strengths (MPa) were in the decreasing order: (CS) 75/25 (277.9 + 12) > 70/30 (270.3 + 7.2) > 60/40 (187.7 + 4.5) > 50/50 (113.1 + 4.4), and (DTS) 75/25 (59.2 + 7.8) > 70/30 (54.3 + 6.1) > 60/40 (34.1 + 2.9) > 50/50 (17.1 + 2.0), where there were no significant differences in both CS and DTS between 75/25 and 70/30 (p > 0.05).
  • FIG. 2 shows the CS of experimental and FUJI II LC cements with and without BAG after being conditioned in SBF for 24h.
  • the CS (MPa) was in the decreasing order: (1) For FUJI II LC cement, FIILC3.2 (212.7 + 15) > FIILC3.2 (10) (127.0 + 1.5) > FIILC2.7 (10) (98.9 + 2.8) > FIILC2.7 (15) (35.3 + 3.7) > FIILC2.7 (20) (0) (p ⁇ 0.05); (2) For experimental cement, EXP2.5 (270.5 + 6.1) ⁇ EXP2.7 (270.3 + 7.2) > EXP2.5 (10) (239.2 + 3.9) ⁇ EXP2.7 (10) (234.9 + 4.5) > EXP2.5 (15) (196.9 + 3.8) > EXP2.7 (15) (164.1 + 6.4) > EXP2.7 (20) (85.5 + 6.5), where there were no significant differences between EXP2.5 and EXP2.7 and between EXP2.5
  • Table 2 shows the mean values and standard deviations of yield compressive strength (YS), modulus, ultimate compressive strength (UCS), DTS and Knoop hardness number (KHN) of FUJI II LC and the experimental cements with and without BAG after being conditioned in SBF for 24h.
  • FIILC3.2 > FIILC3.2 (10) > FIILC2.7 (10).
  • the decreasing order for KHN was EXP2.5 > EXP2.7 > EXP2.7 (10) > EXP2.5 (15) > EXP2.7 (15).
  • Figure 3 shows the effect of the experimental cement aging in SBF on CS.
  • the experimental cements with and without BAG were conditioned in SBF for up to 3 months.
  • the data were collected at 1 h, 1 day, 1 week, 1 month and 3 months for CS evaluation.
  • the results indicate that all the cements showed a pattern of increased CS over time.
  • Table 3 shows the details of strength changes of the experimental cements in the course of aging on behalf of YS, modulus and UCS. All the YS, modulus and UCS data showed an increased pattern.
  • EXAMPLE 8 Evaluation of Dentin Surface. After being conditioned in SBF for two weeks, the dentin surfaces, either directly bonded to the BAG-containing experimental cements or immersed in SBF with the BAG-containing experimental cements, were examined by SEM. The photographs of dentin surfaces after being treated with the BAG-containing experimental cements in SBF, in comparison with those of the dentin surface after being immersed in SBF alone without any BAG or BAG-containing cement, reveal the following. The photographs of the dentin surfaces detached from the BAG-containing experimental cements EXP2.7 (10), EXP2.7 (15) and EXP2.5 (15), after being immersed in SBF, clearly show calcium phosphate crystals on the surface, except for the blocked dentin tubules.
  • Schemes l(a)-l(c) describe illustrative syntheses: (a) Synthesis of the 4-arm PAA: (1) Synthesis of the 4-arm BIBB initiator; (2) Synthesis of the 4-arm poly(t-BA) via ATRP; and (3) Hydrolysis of the 4-arm poly(t-BA); (b) Crosslinking either IEM or GM onto the 4-arm PAA; (c) Chemical structure of HEMA.
  • n is in each instance an independently selected integer, which when selected collectively corresponds to an average molecular weight (M n ) of the polymer in the range from about 1,000 to about 50,000.
  • the integers n are values that collectively correspond to an average molecular weight (M n ) of the polymer in the range from about 5,000 to about 30,000, or in the range from about 9,000 to about 22,000.
  • the preparation described in Scheme l(b) may be used for other polymer core initiators and for other acrylates, by changing the starting compounds to those desired.
  • EXAMPLE 10 Synthesis of the 4- Arm Poly(acrylic Acid) via ATRP. To a flask containing dioxane (5.0 g or 0.056 mole), 4-arm initiator (1% by mole), PMDETA (3%, ligand) and t-BA (5.0 g or 0.04 mole) were charged. The CuBr (3%) was incorporated under N 2 purging after the above solution was degassed and nitrogen-purged by three freeze-thaw cycles. The solution was then heated to 120 0 C to initiate the ATRP. FT-IR was used to monitor the reaction. After the polymerization was completed, the poly(t-BA) polymer was precipitated from water.
  • 4-arm initiator 1% by mole
  • PMDETA 3%, ligand
  • t-BA 5.0 g or 0.04 mole
  • X is NH-CH 2 -CH 2 -O (IEM) or 0-CH 2 -CH(OH)-CH 2 -O (GM); and wherein x, y, and n are as described herein, an independently selected integer in the range from 1 to about 4.
  • IEM NH-CH 2 -CH 2 -O
  • GM 0-CH 2 -CH(OH)-CH 2 -O
  • n is in each instance an independently selected integer, which when selected collectively corresponds to an average molecular weight (M n ) of the polymer in the range from about 1,000 to about 50,000.
  • the integers n are values that collectively correspond to an average molecular weight (M n ) of the polymer in the range from about 5,000 to about 30,000, or in the range from about 9,000 to about 22,000.
  • x and y are integers, each of which is in each instance independently selected. It is therefore to be understood that the structures shown in Scheme l(b) correspond to a variety of arrangements of the PAA and crosslinked PAA fragments.
  • the values of each x, y, and n are such that a random polymeric chain results, or a statistically distributed polymeric chain results, where for example, the values of x and y in each case are small, such as less than 10, or less than 5.
  • the values of each x, y, and n are such that the PAA and crosslinked PAA fragments form a graft polymer or block copolymer, where for example, the values of x and y in each case are large, such as greater than 10, or greater than 20.
  • each x, y, and n are diverse such that the PAA and crosslinked PAA fragments form random sections adjacent to block copolymeric sections.
  • the preparation described in Scheme l(b) may be used for other polymer core initiators, for other acrylates, and for other crosslinking molecules by changing the starting compounds to those desired. It is therefore further appreciated that the nature of these numerous possible polymeric chain arrangements will vary with the selection of the polymer core initiators, the acrylates, and the crosslinking molecules.
  • COMPARATIVE EXAMPLE Synthesis of the Linear PAA via Conventional Free-Radical Polymerization. To a flask containing AIBN and THF, a mixture of AA and THF was added dropwise. Under a nitrogen blanket, the reaction was initiated and run at 62 0 C for 10 h. After the reaction was completed, the PAA was purified by precipitation using ether and drying in a vacuum oven. Additional synthetic details are described by Xie, D., Faddah, M., Park, J.G., "Novel amino acid modified zinc polycarboxylates for improved dental cements," Dent. Mater., 21:739-748 (2005).
  • EXAMPLE 13 Characterization of the Initiator and Polymers.
  • the synthesized 4-arm initiator was characterized by melting point identification, FT-IR spectroscopy and nuclear magnetic resonance (NMR) spectroscopy.
  • the 4-arm polymers were characterized by FT-IR,
  • M n The number average molecular weight (M n ) was determined using a vapor pressure osmometer (K-7000, ICON Scientific, Inc., North Potomac, MD). The viscosity of the liquid formulated with the polymer and distilled water (50:50, by weight) was determined at 25 and 40 0 C using a programmable cone/plate viscometer (RVDV-II + CP, Brookfield Eng. Lab. Inc., Middleboro, MA).
  • EXAMPLE 14 Formulation and Preparation of Specimens for Strength Tests.
  • A Self-cured specimens. A two-component system (liquid and powder) was used to formulate the self-cured cements, as described by Kao, E. C, Culbertson, B. M., Xie, D., "Preparation of glass-ionomer cement using N-acryloyl-substituted amino acid monomers: evaluation of physical properties," Dent. Mater., 12:44-51 (1996). The liquid was prepared by simply mixing either 4- arm PAA or linear PAA with distilled water (50:50, by weight). FUJI II glass powder was used for making cements.
  • the powder/liquid (PfL) was 2.7/1 (by weight, as recommended by the manufacturer).
  • the light-cured cements were also formulated with a two-component system (liquid and powder), as described by Xie, D., Chung, L-D., Wu, W., Lemons, J., Puckett, A., Mays, J., "An amino acid modified and non-HEMA containing glass- ionomer cement," Biomaterials, 25(10): 1825-1830 (2004).
  • the liquid was formulated with either IEM-crosslinked or GM-crosslinked polymer, water, 0.7% CQ (photo-initiator, by weight), 1.4% DC (activator) and 0.05% HQ (stabilizer).
  • FUJI II LC glass powder was used to formulate the cements with a powder/liquid (PfL) ratio of 2.7.
  • FUJI II LC kit with a P/L ratio of 3.2 was used as control.
  • Specimens were fabricated at room temperature according to these published protocols. Briefly, the cylindrical specimens were prepared in glass tubing with dimensions of 4 mm diameter by 8 mm length for compressive strength (CS) and 4 mm diameter by 2 mm length for diametral tensile strength (DTS) tests. A split Teflon mold with dimensions of 3 mm in width x 3 mm in thickness x 25 mm in length was used to make rectangular specimens for flexural strength (FS) test. A transparent plastic window was used on top of the split mold for light exposure. Specimens were removed from the mold after 15 min in 100% humidity, and conditioned in distilled water at 37 0 C for 24 h. Light-cured specimens were exposed to blue light (EXAKT 520 Blue Light Polymerization Unit, 9W/71, GmbH, Germany) for 1 min before conditioned in 100% humidity.
  • EXAKT 520 Blue Light Polymerization Unit 9W/71, GmbH, Germany
  • 1722 and 1636 are two most characteristic peaks associated with carbonyl and carbon-carbon double bond, respectively.
  • disappearance of the peak at 1636 cm “1 in the spectrum for the 4-arm poly(t-BA) confirmed the completion of polymerization.
  • a broad and significant peak at 3600- 2300 cm “1 and a strong but wider peak at 1714 cm “1 could be observed as compared to poly(t- BA).
  • the former is the typical peak for hydroxyl group on carboxylic acids (OH stretching) whereas the latter is the characteristic peak for carbonyl stretching on PAA.
  • the 1 H NMR spectra for the 4-arm BIBB, 4-arm PAA, IEM-crosslinked 4-arm PAA and GM-crosslinked 4-arm PAA showed the following.
  • the chemical shifts of the 4-arm BIBB initiator were found as follows (ppm): a: 4.3 (CH 2 ) and b: 1.9 (CH 3 ).
  • the chemical shifts of the 4-arm PAA were (ppm): a: 12.25 (COOH); b: 3.4 (CH 2 ); c: 2.25 (CH); d: 1.8 and 1.55 (CH 2 ); and e: 1.1 (CH 3 ).
  • a single peak at 2.50 (between b and c) was the chemical shift for solvent DMSO. All the spectra contained this peak.
  • the chemical shift for COOH on GM-crosslinked 4-arm PAA was weak but broad.
  • the characteristic chemical shifts at 3.25, 5.70 and 6.10 identified the difference between the 4-arm PAA and GM-crosslinked 4-arm PAA.
  • EXAMPLE 17 Synthesis and Hydrolysis of the 4-Arm poly(t-BA).
  • the 4-arm PAA was prepared by hydrolysis of the poly(t-BA) in a mixed solvent of dioxane and aqueous HCl (37%) for 8-12 h under refluxed condition, followed by dialysis against water until the pH reached neutral. Additional synthetic details are described by L. Stanislawski, X. Daniau, A. Lauti A., and M. Goldberg, "Factors responsible for pulp cell cytotoxicity induced by resin-modified glass ionomer cements," J. Biomed. Mater. Res.,
  • Table 4 shows the MW, conversion and viscosity of the three 4-arm PAAs and one linear PAA.
  • the MWs of the 4-arm PAAs synthesized via ATRP were 15,701, 18,066 and 21,651 Daltons whereas the MW of the linear PAA synthesized via conventional free-radical polymerization was 9,704.
  • the conversions of the monomer to polymer were determined using FT-IR spectra and they were all greater than 97%.
  • the viscosities were measured using a cone & plate viscometer and shown in Table 4.
  • EXAMPLE 18 Synthesis of the IEM-Crosslinked and GM-Crosslinked 4- Arm PAAs. The reaction between IEM and carboxylic acid on PAA took only two hours to complete. Disappearance of the isocyanate group at 2250 cm "1 by FT-IR monitoring confirmed the completion of the reaction. The reaction between GM and carboxylic acid on PAA took about fourteen hours to complete. Disappearance of the epoxy group on GM at 761 cm "1 confirmed the completion of the crosslinking reaction. The completion of the crosslinking for both reactions was also confirmed by the fact that yields were greater than 95%. EXAMPLE 19. Selection of the 4- Arm PAA for Methacrylate Cros slinking.
  • the cement B with MW of 18,066 showed the highest yield CS (YCS, 190.0 MPa), ultimate CS (UCS, 212.2 MPa) and modulus (M, 8.33 GPa), followed by the A (160.9, 184.1 and 8.11) and the C (157.1, 176.9 and 7.74). Due to its suitable viscosity and highest CS, the polymer B was selected for methacrylate crosslinking.
  • the CS values for D were 167 MPa in YCS, 183 MPa in UCS and 7.04 GPa in M. It was observed that making the specimens from both C and D was very difficult because of their high solution viscosities. Without being bound by thoery, it is believed that the higher viscosities of both C and D is attributable to strong hydrogen bonding.
  • EXAMPLE 20 COMPARATIVE EXAMPLE.
  • Crosslinking of IEM or GM onto the 4- Arm PAA for Light-Curable GICs may be incorporated, as described by Xie, D., Chung, L-D., Wu, W., Lemons, J., Puckett, A., Mays, J., "An amino acid modified and non-HEMA containing glass-ionomer cement," Biomaterials, 25(10):1825-1830 (2004); Xie, D., Faddah, M., Park, J.G., "Novel amino acid modified zinc polycarboxylates for improved dental cements," Dent.
  • Table 5 shows the effects of different comonomer and grafting agent on compressive properties.
  • Codes E, F, G and H stand for the cements crosslinked with 35%, 35%, 50%, and 50% GM and mixed with HEMA, MBA, HEMA and MBA, respectively.
  • E and F the MBA, acid-containing comonomer
  • YCS the M and UCS.
  • both YCS and M increased even more significantly. Without being bound by theory, it is believed that this increase can be attributed to formation of salt-bridges contributed by MBA, and it is appreciated that salt-bridges often make the cements more brittle and it is also appreciated that brittle materials are high in yield strength and modulus.
  • the same principle may be applied to G and H. By comparing E and G or F and H, a higher grafting ratio gave higher UCS but not necessarily YCS and M.
  • the 50% IEM-crosslinked cement with MBA (175.1 MPa in YCS, 6.5 GPa in modulus and 257 MPa in UCS) was 22%, 20% and 21% higher than corresponding the 50% GM-crosslinked cement with MBA (144.1, 5.4 and 213.2).
  • this difference may be attributed to the difference between IEM and GM-crosslinked cements, because the former contains more hydrophobic IEM-crosslinked 4-arm PAA whereas the latter contains more hydrophilic GM- crosslinked 4-arm PAA due to the extra hydroxyl groups, andthese hydroxyl groups can keep more water around, which make the cements relatively weaker in strength because the cement somehow behaves like a hydrogel material.
  • FIG. 7a shows that the IEM-crosslinked cement exhibited significantly higher FS, DTS, and CS than FUJI II LC.
  • the GM-crosslinked cement exhibited significantly higher FS and statistically similar DTS and CS compared to FUJI II LC.
  • Figure 7b shows the CS, DTS and FS values for Example M (GM-crosslinked 4-arm PAA) compared to commercial FUJI II, FUJI II LC, and VITREMER cements.
  • the light-curable 4-arm star-shape PAA was synthesized via ATRP and showed a lower viscosity as compared to the corresponding linear counterpart that was synthesized via conventional free -radical polymerization. Without being bound by theory, it is suggested that the spherical nature of the 4-arm star-shape PAA may account for the difference in observed viscosity. Both GM-crosslinked and IEM-crosslinked variants of the 4-arm PAA-constructed LCGICs showed significantly high mechanical strengths than conventional cements. It was also observed that the MBA-containing cement variants exhibited much higher CS than the HEMA- containing cement variants. Without being bound by theory, it is also suggested that a salt-bridge contribution of the MBA may account for the improved CS.
  • the IEM-crosslinked cement variants showed much higher mechanical strengths than the GM-crosslinked cement variants. Without being bound by theory, it is also suggested that a hydrophobicity difference between the two corresponding polymers may account for the improved mechanical strengths.
  • the selected cements described herein showed 13% improvement in CS, 178% improvement in DTS, and/or 123% improvement in FS over the conventional cement prepared from FUJI II LC.
  • the results in Table 7 show that the polyfunctional core molecules and prepolymer compounds described herein, including poly(acrylic acid) crosslinked with pendent methacrylate to formulate the LCGIC improves the mechanical strengths and wear resistance of the GICs.
  • the 4-arm star poly(acrylic acid) Example was improved by 48% in CS, 76% in DTS, 95% in FS and 60% in FT higher than FUJI II LC cement.
  • the Example also showed higher wear-resistance (97.5 ⁇ m 3 cycle "1 ) than FUJI II LC (11525 ⁇ m 3 cycle "1 ).
  • the Example was 5% lower in CS, 20% higher in DTS, 20% lower in FS and 15% lower in FT than Filtek P60 posterior composite resin, it showed surprisingly improved (97.5 ⁇ m 3 cycle "1 ) wear-resistance than Filtek P60 (545 ⁇ m 3 cycle "1 ).
  • the 4-arm and FUJI II LC GICs for CS, DTS, FS, and FT tests were conditioned in distilled water at 37 0 C for 1 week prior to testing.
  • RMGICs Significance of Crosslinking of GM onto the 4-Arm PAA. It is believed that the main difference between RMGICs and conventional GICs is their liquid composition as described by A. D. Wilson, "Resin-modified glass-ionomer cement," Int. J. Prosthodont, 3:425-429 (1990).
  • the liquid in RMGICs is composed of HEMA, photo-initiators, water, and a poly(alkenoic acid) having pendent in situ polymerizable methacrylate on its backbone or a mixture of poly(alkenoic acid) and methacrylate-containing monomer/oligomer.
  • the liquid in conventional GICs consists of only hydrophilic poly(alkenoic acid) and water.
  • amphiphilic monomers such as HEMA have to be incorporated into the RMGIC liquid formulation to enhance the solubility of the hydrophobic poly(alkenoic acid) in water. It is appreciated that, without these amphiphilic small molecules like HEMA, it is difficult to formulate RMGICs by using current technologies. It has been reported that crosslinking GM onto the poly(alkenoic acid) backbone can increase water- solubility of the polyacid because of introduction of hydroxyl groups as compared to 2- isocyanatoethyl methacrylate (IEM)-crosslinked poly(alkenoic acid), as described by D. Xie, J. G. Park, and M. Faddah, J.
  • IEM 2- isocyanatoethyl methacrylate
  • the cements C, D and E represent the 35% GM- crosslinked 4-arm PAAs with the PAV ratio at 50/50, 60/40 and 75/25. It is observed that increasing PAV ratio significantly increased yield compressive strength (YCS), modulus (M) and ultimate compressive strength (UCS), indicating that a higher polymer concentration may enhance the mechanical strength of the relatively hydrophilic GM-crosslinked PAA cement.
  • YCS yield compressive strength
  • M modulus
  • UCS ultimate compressive strength
  • the cement C showed the lowest YCS (47.5 MPa), M (2.65 GPa) and UCS (68.5 MPa), suggesting that at 50/50, the hydrophilic characteristic of the GM-crosslinked PAA prevails and the cement behaves like a hydrogel.
  • METHOD EXAMPLE Effect of Glass Powder/Polymer Liquid Ratio on Compressive Properties. It is appreciated that the glass powder/polymer liquid (PfL) ratio is an important parameter in formulating GICs. It is also appreciated that a higher P/L ratio may result in higher mechanical strengths, especially CS, but it may also shorten working time. It is also appreciated that working time is less of an issue for a light-curable GIC system, and therefore a higher P/L ratio may be used in LCGICs, such as the filler FUJI II LC (3.2). The effect of three P/L ratios (2.2, 2.7 and 3.0) on CS is shown in Table 9.
  • the FS of the optimal experimental cement was measured and compared to the measured CS, DTS and FS of commercial FUJI II LC cement.
  • the strengths of both cements were determined after conditioning in distilled water at 37 0 C for 24 h.
  • the CS, DTS and FS of illustrative cements described herein were compared to FUJI II LC.
  • P/L ratio 3.2.
  • the light-cured cement described herein showed significantly higher CS (256.0 ⁇ 5.8 MPa), DTS (39.5 ⁇ 4.6 MPa) and FS (98.4 ⁇ 5.0 MPa) as compared to corresponding 228.2 + 6.4, 21.2 + 1.1 and 44.2 + 3.4 for FUJI II LC.
  • Example M has a comonomer-free and pendent hydroxyl group-containing system
  • the polymer liquid contains highly concentrated GM-crosslinked star- shape poly(AA) in water, which provides not only a large quantity of carboxyl groups for salt- bridge formations but also a substantial amount of carbon-carbon double bond for covalent crosslinks.
  • both FUJI II LC and VITREMER contain HEMA and/or other low MW methacrylate comonomers. The effect of aging on Example M, FUJI II, FUJI II LC and
  • VITREMER on CS over a period of two weeks is shown in Figure 9. As shown in Figure 9, they have a lower strength as compared to Example M. FUJI II showed relatively higher CS but lower DT and FS as compared to FUJI II LC and VITREMER. Conventional GICs do not produce any covalent crosslinks except for salt-bridges (ionic bonds) when they are set. Table 10. YS, modulus, UCS in the course of aging.
  • Example METHOD EXAMPLE In Vitro Cytotoxicity.
  • the in vitro cytotoxicity of Example M was studied using Balb/c 3T3 mouse fibroblast cells. It has been reported that RMGICs are more cytotoxic than conventional GICs (see, Leyhausen, G., Abtahi, M., Karbakhsch, M., Sapotnick, A., Geustsen, W., "Biocompatibility of various light-curing and one conventional glass-ionomer cements," Biomaterials, 19:559-564 (1998)).
  • Unpolymerized monomers my also be responsible for pulp cell cytotoxicity (Stanislawski, L., Daniau, X., Lauti, A., Goldberg, M., "Factors responsible for pulp cell cytotoxicity induced by resin-modified glass ionomer cements," J. Biomed. Mater. Res., 8(3):277-88 (1999)).
  • RMGICs have been shown to cause the highest cytophatic effects on odontoblast cell line (MDPC-23) (de Souza Costa, CA. , Hebling, J., Garcia-Godoy, F., Hanks, CT. , "In vitro cytotoxicity of five glass-ionomer cements," Biomaterials, 24:3853-3858 (2003)).
  • Example M was not expected to show any significant cytotoxicity and its in vitro cytotoxicity was expected to be as low as that of those conventional GICs because that example does not contain any comonomers in its formulation.
  • Figure 10 shows the cell viability after the cells were cultured with the eluates of Example M, FUJI II, FUJI II LC, VITREMER, and blank, i.e., negative control (NC).
  • Example M showed the highest cell viability after cell exposure to both 3-day and 7-day eluates.
  • VITREMER showed the lowest viability to the 3- day eluate whereas FUJI II LC showed the lowest viability to the 7-day eluate. This may be attributed to the fact that Example M contains no comonomers before polymerization and thus no leachables (unreacted monomers) should be expected.
  • FUJI II showed very little cytotoxicity because it is a conventional GIC, which does not contain any leachable monomers or other additives such as photo-initiators and activators (Wilson, A.D., McLean, J.W., "Glass- ionomer cements," Chicago, IL, Quintessence Publ Co., 1988; Davidson C. L., Mj ⁇ r. LA. , "Advances in glass-ionomer cements," Chicago, IL, Quintessence Publ. Co., 1999). VITREMER cement was reported to be the most cytotoxic among several tested cements including FUJI II LC (de Souza Costa, CA.
  • the polymers with different molecular weights (MW) were prepared by changing the amount of CTA used. The final products were freeze-dried, ground, and stored prior to use. The yields were greater than 96% for all the polymers synthesized in the study. It is to be understood that the compounds illustrated in this example may be, as described herein, converted into the corresponding crosslinkable polyfunctional prepolymers described herein, where Q a is where X is illustratively NH-CH 2 -CH 2 -O (IEM) or 0-CH 2 -CH(OH)-CH 2 -O (GM); and a, b, c, d, e, and n are as described herein.
  • IEM NH-CH 2 -CH 2 -O
  • GM 0-CH 2 -CH(OH)-CH 2 -O
  • EXAMPLE 25 Characterization of Monomers and Polymers.
  • the synthesized chain-transfer agents were characterized by FT-IR and NMR spectroscopy.
  • the polymers were characterized by FT-IR and gel permeation chromatography (GPC).
  • FT-IR spectra were obtained on a FT-IR spectrometer (Mattson Research Series FT/IR 1000, Madison, WI).
  • 1 H NMR spectra were obtained on a NMR spectrometer (Varian-Inova narrow-bore 500 MHz NMR, Varian, Inc., Palo Alto, CA) using deuterated methyl sulfoxide as a solvent.
  • the polymers were treated with diazomethane, which was generated from DIAZALD reacted with potassium hydroxide (KOH) in water/ethanol solution at 65 0 C, to obtain partially esterified products, having solubility in THF for molecular weight estimation.
  • KOH potassium hydroxide
  • Molecular weights were estimated on a Waters GPC unit (Model 410 differential refractometer, Waters Inc., Milford, MA), using standard GPC techniques and polystyrene standards. THF was used as a solvent.
  • EXAMPLE 26 Viscosity Determination. The viscosity of the liquid formulated with the polymer and distilled water was determined at 23 0 C using a programmable cone/plate viscometer (RVDV-II + CP, Brookfield Eng. Lab. Inc., Middleboro, MA).
  • EXAMPLE 27 Formulation and Preparation of Specimens for Strength Tests.
  • a two-component system liquid and powder was used to formulate the cements.
  • the liquid was prepared by simply dissolving the polymer in distilled water.
  • the powder was FUJI II glass powder for conventional GIC.
  • Specimens were fabricated at room temperature according to the protocol published by Wu et al., Eur. Polym. J., 39:959-968 (2003).
  • the cylindrical specimens were prepared in glass tubing with dimensions of 4 mm diameter by 8 mm length for compressive strength (CS) and 4 mm diameter by 2 mm length for diametral tensile strength (DTS) tests. Specimens were removed from the mold after 15 minutes in 100% humidity, and conditioned in distilled water at 37 0 C for 24 h prior to testing.
  • CS compressive strength
  • DTS diametral tensile strength
  • the significant and strong peaks at 1735 or 1736 for carbonyl and 1273 or 1276 for thiol groups confirmed the formation of the 3-, 4- and 6-arm CTAs.
  • EXAMPLE 29 The 1 H NMR spectra for mercaptoacetic acid, pentaerythritol, 4- arm CTA and 4-arm poly(AA-co-IA) showed the following chemical shifts (ppm): (1) Mercaptoacetic acid: a: 7.58 (COOH); b: 3.56 (CH 2 ); and c: 3.87 (S-H). (2) Pentaerythritol: a: 4.22 (CH 2 ) and b: 3.36 (O-H). (3) 4- Arm CTA: a: 4.18 (CH 2 ); b: 3.35 (S-H); and c: 2.94 (CH 2 ). (4) 4- Arm poly(AA-co-IA): a: 12.25 (COOH).
  • EXAMPLE 30 The molecular weights of the synthesized polymers and the viscosities of the polymer aqueous solutions were determined using GPC and a viscometer, respectively. Table 1 shows the theoretical MWs, measured number average MW (Mn), measured weight average MW (Mw), MW distribution (PDI) of the synthesized polymers and viscosity values of the polymers in water (50/50, by weight). In the case of the 4-arm CTA, the measured Mn was quite similar to the calculated MW, except for 15K and 18K. The measured Mw shows the trend of consistency with the calculated MW. The PDI values were between 1.33 and 1.93.
  • the viscosities (38.6 to 1439.5 cp) of these polymers were directly proportional to the measured Mw (7541 to 65130), i.e., the higher the MW the higher the viscosity.
  • the effect of arm number was also compared in Table 1.
  • the 4-arm star polymer (18K) showed a relatively lower viscosity as compared to the 3-arm polymer (18K) under the similar MW and so did the 6- arm (18K) polymer. It seems that the more arms that the polymer has, the lower the viscosity that the polymer exhibits.
  • EXAMPLE 31 Formulation and Property Determination.
  • these parameters include MW of polymer, water content in formulation (polymer/water or P/W ratio), glass powder/liquid (P/L) ratio, etc.
  • the effects of arm number of CTA, MW of the formed polymer, P/W ratio, P/L ratio and aging were evaluated.
  • Table 2 shows the effect of arm number of CTA on compressive properties and viscosity.
  • the linear polymer showed the lowest YS, modulus, UCS and highest viscosity
  • the 6-arm star polymer showed the highest YS and lowest viscosity
  • the 4-arm star polymer showed the highest modulus and UCS.
  • 1 CTA chain-transfer agent
  • FIG. 12 shows the effects of MW and viscosity of the 4-arm star polymer on mechanical strengths of the cements.
  • the viscosity values (cp) were in the decreasing order of 36K (1439.5) > 18K (243.2) > 15K (181.7) > 12K (126.9) > 9K (87.2) > 4.5K (38.6).
  • Both CS (MPa) and DTS (MPa) were in the decreasing order of 15K (225.7 + 5.6) > 36K (214.9 + 2.5) > 18K (214.4 + 7.2) > 9K (212.8 + 8.1) > 12K (210.2 + 5.6) > 4.5K (184.7 + 2.5) for CS and 36K (29.6 + 2.1) > 18K (25.4 + 0.7) > 15K (23.8 + 0.6) > 9K (23.6 + 1.6) > 12K (23.5 + 2.0) > 4.5K (19.8 + 0.3) for DTS.
  • the viscosity values (cp) were in the decreasing order of 70/30 (20640) > 60/40 (1252) > 50/50 (181.7) > 40/60 (31.8).
  • Increasing PAV ratio dramatically increased the viscosity but significantly decreased CS.
  • the 50/50 showed the highest CS and second to the highest DTS.
  • the 60/40 showed the highest DTS whereas the 40/60 showed the lowest CS and DTS.
  • higher content of polymer leads to higher strengths (Xie et al., Dent. Mater., 23:994-1003 (2007)); however, it is appreciated that too much polymer can cause difficulty in mixing, which in turn leads to a reduction of strengths. From the results, the 50/50 appears to be the optimal PAV ratio among all the PAV ratios studied based on both strength and viscosity.
  • the CS values of the 4-arm star polymer-composed cements with MWs of 9K, 15K and 36K were measured after being conditioned in water for 1 h, 1 day, 1 week, 1 month and 3 month. It is apparent that all the cements showed a significant increase (40 to 57%) in CS from 1 hr to 1 day. After that a slower increase (1.6%, 6% and 13% for 9K, 15K and 36K) in CS was noticed during a week. Finally, the cements with 9K, 15K and 36K showed 62%, 64% and 79% increase in CS from 1 hr to 3 months, respectively, with the final values of 270.1, 293.3 and

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Abstract

La présente invention concerne des composés polyfonctionnels et des compositions de ciment de verre ionomère, utiles dans diverses réparations dentaires, osseuses et orthopédiques, dont l'augmentation et la restauration.
PCT/US2009/040482 2008-04-15 2009-04-14 Composés polyfonctionnels et compositions et procédés de ciment de verre ionomère destinés à être utilisés comme matériaux d'implants Ceased WO2009129221A1 (fr)

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WO2017159552A1 (fr) * 2016-03-17 2017-09-21 富士フイルム株式会社 Procédé de production d'un composé thiol polyfonctionnel, composé thiol polyfonctionnel, composition durcissable, et procédé de production d'une composition durcissable
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