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WO2025136359A1 - Ballonnet revêtu de médicament endobronchique - Google Patents

Ballonnet revêtu de médicament endobronchique Download PDF

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Publication number
WO2025136359A1
WO2025136359A1 PCT/US2023/084799 US2023084799W WO2025136359A1 WO 2025136359 A1 WO2025136359 A1 WO 2025136359A1 US 2023084799 W US2023084799 W US 2023084799W WO 2025136359 A1 WO2025136359 A1 WO 2025136359A1
Authority
WO
WIPO (PCT)
Prior art keywords
peg
scoping
scoping device
inflatable balloon
polyglyceryl
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.)
Pending
Application number
PCT/US2023/084799
Other languages
English (en)
Inventor
Matthew CARTRIGHT
Summer L. FORD
Genevieve MESSINA
William E. Parmentier
Kyra TEMPLE
Peng Zheng
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.)
Bard Peripheral Vascular Inc
Original Assignee
Bard Peripheral Vascular Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Bard Peripheral Vascular Inc filed Critical Bard Peripheral Vascular Inc
Priority to PCT/US2023/084799 priority Critical patent/WO2025136359A1/fr
Publication of WO2025136359A1 publication Critical patent/WO2025136359A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00064—Constructional details of the endoscope body
    • A61B1/00071—Insertion part of the endoscope body
    • A61B1/0008—Insertion part of the endoscope body characterised by distal tip features
    • A61B1/00082—Balloons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00064—Constructional details of the endoscope body
    • A61B1/00071—Insertion part of the endoscope body
    • A61B1/0008—Insertion part of the endoscope body characterised by distal tip features
    • A61B1/00101—Insertion part of the endoscope body characterised by distal tip features the distal tip features being detachable
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/012—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor characterised by internal passages or accessories therefor
    • A61B1/018—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor characterised by internal passages or accessories therefor for receiving instruments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/01—Introducing, guiding, advancing, emplacing or holding catheters
    • A61M25/0105—Steering means as part of the catheter or advancing means; Markers for positioning
    • A61M25/0133—Tip steering devices
    • A61M25/0147—Tip steering devices with movable mechanical means, e.g. pull wires
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/005—Flexible endoscopes
    • A61B1/009—Flexible endoscopes with bending or curvature detection of the insertion part
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M2025/1043—Balloon catheters with special features or adapted for special applications
    • A61M2025/105—Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M2025/1043—Balloon catheters with special features or adapted for special applications
    • A61M2025/1086—Balloon catheters with special features or adapted for special applications having a special balloon surface topography, e.g. pores, protuberances, spikes or grooves

Definitions

  • This disclosure relates to actuable balloons at a distal end of an endobronchial scope with a drug coating thereon to improve site-specific delivery and to methods of the use of the same.
  • FIG. 1 shows a side view of one aspect of the device of the present disclosure.
  • FIG. 2 shows an isolated shape of one aspect of the balloon of the present disclosure.
  • FIG. 3 shows a further isolated shape of one aspect of the balloon of the present disclosure
  • FIG. 4 shows a third isolated shape of one aspect of the balloon of the present disclosure.
  • FIG. 5 shows a cross-sectional side view of an isolated balloon of the present disclosure in contact with tissue.
  • FIG. 6 shows one embodiment of a cross-sectional view of the scoping section of the bronchioscope.
  • FIG. 7 shows a further embodiment of a cross-sectional view of the scoping section of the bronchioscope.
  • FIG. 8 shows an enlarged portion side view of deployment of the balloon.
  • FIG. 9 shows an aspect of angulation of the balloon.
  • FIG. 10 shows a further aspect of angulation of the balloon.
  • FIG. 11 shows an even further aspect of angulation of the balloon.
  • the present disclosure relates to a drug-coated balloon at a distal end of a scoping device, such as a bronchioscope.
  • the balloon is pre-coated with a drug coating layer and is designed to deposit the drug coating on lung tissue within the airways.
  • a scoping device such as a bronchioscope
  • a proximal body and a distal scoping section
  • the body of the device includes controls that are operably connected to the scoping section, frequently through one or more wires, that allow a user to cause the scoping section to bend at one or more points along the scoping section that allows the scoping section as a whole to navigate within organs and anatomical spaces, particularly those with complex geometries.
  • the balloon is operably connected to an inflation means, such that a user can utilize a bronchioscope as usual to navigate a distal end to a desired position. Once in place within a subject’s lungs, the operator can activate the inflation means and cause the balloon to inflate in situ within the subject’s lung tissue.
  • a bronchioscope includes angulation means such that a distal section can curve.
  • the distal section can include one or more pivot points or pins that allow the section to curve.
  • angulation wires that extend from a user’s access point, such as a knob or controller, to the distal section.
  • the two or more angulation wires may be connected between a controller and the distal section to allow for further angulation of the section.
  • the distal section angulation wire(s) are threaded internally inside the body of the scope.
  • the present disclosure includes an inflatable balloon at a distal end of a bronchoscope.
  • the distal end refers to that end of a bronchoscope distal from the control end or distal from a user or the end that leads the scoping when in use.
  • the inflatable balloon is operably connected to an inflation means, such that a user can inflate the balloon in situ within a subject.
  • the inflation means may include a catheter placed within an opening of the balloon to allow for an inflation gas or fluid to enter the balloon and inflate in situ.
  • the inflation means is operably connected to a gas or fluid source to allow a user to direct or control the entry thereof into and out of the balloon.
  • the inflation means can be arranged to allow for the balloon to deflate. It will be appreciated that in some aspects, deflating the balloon may be desirable before trying to withdraw the distal end of the bronchoscope from a subject’s airways.
  • the inflatable balloon is connected to an inflation means such as a pump.
  • a catheter may connect the pump to a hole in the balloon to allow for the inflation thereof in situ.
  • the pump may be operably connected to a pressure gauge to provide feedback to a user as to the pressure within the balloon during and while inflated.
  • the catheter connecting the pump to the balloon may be threaded through or housed within the scope or a portion thereof.
  • the scope may include a port at or in relative proximity to controls of the scope, such that a user can feed the inflatable balloon and catheter into the scope.
  • the distal end of the scope may include a further port or hole such that the inflatable balloon can emerge prior to or during inflation.
  • the distal end includes a port with an operable cover, such that a user can withdraw the cover or slide the cover to allow for the inflatable balloon to exit the scope in situ.
  • the inflatable balloon includes one or more cables attached directly or indirectly to a wall thereof.
  • the cable(s) may be attached to an internal wall or to an external wall.
  • the cables can be arranged such that they can be threaded along or inside the catheter, such that the cables can be pulled by a user.
  • the cables may be connected operably to a control unit that allows a user to applying a pulling force thereto.
  • the inflatable balloon includes a cable attached to a point on the exterior surface thereof. Pulling on the cable by the user in situ can thereby cause the side of the balloon where the cable is attached to rotate or move in response to the applied force.
  • the applied force can allow the balloon to roll or rotate across the tissue.
  • the drug coating on the surface of the balloon can therefore better deposit as the balloon is drawn by the cable(s) across the tissue.
  • FIG. 1 depicted is a side view partial cross-section of a bronchioscope 100. Included are the proximal end 110 and the distal end 120 and the scoping section 130 that includes one or more points that allow the scoping section 130 to bend in response to a user operating controls 140 at the proximal end 110.
  • an inflatable balloon 150 connected to a catheter 160 and an inflation means 170 (e.g. pump).
  • the inflation means 170 can operate the inflation/deflation of the inflatable balloon 150 through a port 180 in the bronchioscope 100.
  • one or more cables 190 that connect parts of the inflatable balloon 150 to the controls 140 to allow a user to cause movement and/or angulation of the inflated inflatable balloon 150 in situ.
  • FIG. 2 shows the inflatable balloon 150 and connected cable(s) 190.
  • the inflatable balloon 150 is in an almost 3D “U” shape or horseshoe shape, with the cables 190 connected to the sides of the inflatable balloon 150, such that a pulling force applied to one cable 150 will move and/or angulate the inflated inflatable balloon 150.
  • FIG. 3 shows the inflated inflatable balloon 150 in the shape of a mushroom cap.
  • the shape need not be limited to a convex shape, but may also be plano-convex, sub-globular, umbrate-obtuse, bell-shaped, cone-shaped, kidney-shaped, conical, ovate, flat, and so forth.
  • the cables 190 are connected to one or more points on the edge or side of the inflated inflatable balloon 150.
  • FIG. 4 sets forth a further possible shape configuration for the inflatable balloon 150.
  • the inflated inflatable balloon 150 can be segmented into leaflets or foils.
  • the inflatable balloon 150 is a quatrefoil, though bifoil and trifoil are easily substituted shapes, as are increasing numbers of foils or leaves, such as 5, 6, 7, or higher.
  • the cables 190 are connected to one or more points on the edge or side of the inflated inflatable balloon 150.
  • FIG. 5 shows the inflatable balloon 150 in an angulated position such that the exterior surface 210 of the inflatable balloon 150 has a higher surface area contact with the tissue 220 of the subject in situ.
  • the cable 190 on the as depicted right-side of the inflatable balloon 150 has had a pulling force applied to draw the same as depicted right-side of the balloon toward the user and thereby increasing surface are contact on the as-depicted left side with the tissue 220.
  • FIGs. 6 and 7 show cross-sections of the scoping section of the bronchioscope.
  • the cable(s) 190 can run along the side of the catheter 160 within the scoping section. It will be appreciated that the cable(s) 190 in some aspects may be secured and/or adhered to the exterior of the catheter 160.
  • FIG. 7 shows an alternative arrangement of the scoping section wherein the catheter 160 and the cable(s) 190 are housed within isolated channels along the scoping section.
  • FIG. 8 depicts a side-view of the scoping section 130 with a cutaway and the distal end 120.
  • the cable(s) 190 emerge from the distal end 120 and connect to an exterior surface of the inflated inflatable balloon 150.
  • the one or more points of rotation 230 by which the user can cause the scoping section 130 to bend or articulate in situ.
  • the catheter that operably connects the inflation means to the inflatable balloon 150 to thereby allow a user to control the inflation status, as well as the internal pressure within.
  • the inflatable balloon is coated in at least one coating layer, wherein the coating layer is provided such that when the balloon is inflated in situ, the coating layer can be deposited through contact onto the surface of a desired area of tissue.
  • the inflatable balloon may include one or more chemotherapeutic agents in the coating layer.
  • the bronchoscope as disclosed herein can be maneuvered into a desired location within the subject and the balloon therein is inflated. The scope can optionally move after inflation. The inflated balloon can then be independently moved in situ through operation of the cables connected to one of more sides and/or edges of the balloon. Furthermore, the pressure of the balloon can be adjusted to achieve a desired degree of contact.
  • a lowered internal pressure in the inflated balloon may allow the exterior surface to draw and/or collapse over a desired area.
  • a higher internal pressure may stiffen the exterior surface of the balloon and allow the exterior surface to roll across a desired area of tissue or rock back and forth as different forces are applied on the cables.
  • the inflatable balloon may require a single cable to allow a unilateral movement.
  • two or more cables may be used to increase the mobility of the exterior surface across tissue surface(s) in situ.
  • two opposing cables will allow for a back-and-forth movement across the surface.
  • FIGs. 9, 10, and 11 depict various combinations of forces that can be applied with a two cable system. It will be appreciated that adding in a third, fourth, or more number of cables about the exterior surface and/or edge of the balloon. Further, as shown in FIG. 11, the force applied does not need to be limited to a single cable at any point in time, but can be through multiple points of applied force, which can be of the same of differing amount in intensity or strength.
  • the inflatable balloon is prepared with a coating layer.
  • the coating layer may include a therapeutic.
  • the therapeutic may be included in crystalline form, in amorphous form, or embedded within a microparticle, or combinations thereof.
  • the coating layer may include one or more of an excipient, a surfactant, a pharmaceutically acceptable carrier, a polymer, a vitamin, a mineral, a salt, or similar.
  • the coating layer may include a therapeutic for treatment of a lung condition.
  • the condition may be a lung cancer or tumor thereof.
  • the therapeutic may be selected to treat such, such as with abraxane, adagrasib, afatinib, everolimus, alectinib, pemetrexed, brigatinib, bevacizumab, amivantamab, capmatinib, cemiplimab, ceritinib, crizotinib, ramucirumab, dabrafenib, dacomitinib, docetaxel, doxorubicin, trastuzumab, entrectinib, erlotinib, mobocertinib, pralsetinib, gefitinib, gemcitabine, tremelimumab, ipilmumab, permbrolizumab, lorlatinib, sotorasib, tram
  • and/or phosphodiesterase inhibitor drugs and/or anti-fibrosis drugs and/or kinase inhibitors and/or tyrosine kinase inhibitors and/or receptor tyrosine kinase inhibitors may be selected.
  • Examples may include one or more of paclitaxel, rapamycin, daunorubicin, 5- fluorouracil, doxorubicin, sunitinib, sorafenib, irinotecan, bevasizumab, cetuxamab, biolimus (biolimus A9), everolimus, zotarolimus, tacrolimus, dexamethasone, prednisolone, corticosterone, cisplatin, vinblastine, lidocaine, bupivacaine, bosutinib, ceritinib, crizotinib, gefitinib, ruxolitinib, imatinib, axitinib, nilotinib, trametinib, afatinib, ibrutinib, cabozantinib, imatinib, lenvatinib, sunitinib, regorafeni
  • the coating layer may include microparticles of therapeutic agent(s) and a bioabsorbable polymer.
  • Microparticles may be prepared the evaporation of a solvent with a bioabsorbable/biodegradable polymer and at least one therapeutic therein.
  • the solvent is of dichloromethane (DCM) or ethyl acetate (EtOAc).
  • Polymers may include a network of a poly-glycolic acid (PGA) and a poly-L-lactic acid (PLLA).
  • bioabsorbable polymers that can be utilized in combination or alone for the microparticles include poly caprolactone (PCL), poly-DL-lactic acid (PDLLA), poly(trimethylene carbonate) (PTMC), poly (ester amine)s (PEA), poly(para-dioxanone) (PPDO), poly-2-hydroxy butyrate (PHB), and co-polymers with various ratios thereof.
  • the bioabsorbable polymer may include, either alone or in combination with other bioabsorbable polymers, a polymer combination of lactic acid and glycolic acid, poly-lactic-co-glycolic acid (PLGA).
  • PLGA can be of varying percentages of lactic acid and glycolic acid, wherein the higher the amount of lactide units, the longer the polymer can last in situ before degrading. Additional tunable properties with PLGA concern the molecular weight, with higher weights showing increased mechanical strength.
  • the polymer microparticle is also loaded or embedded with an antioxidant, such as BHT.
  • the coating layer may include a polymer coating, such as a bioabsorbable polymer as set forth herein.
  • the density of the therapeutic or polymer microparticle within the polymer coating is of from about 0.1 to 10 pg/mm 2 .
  • the theapeutic or polymer microparticle is provided on the device in the polymer coating at a density of from about 0.5 to about 5 pg/mm 2 .
  • the dose density of the therapeutic in the coating and/or within each polymer microparticle can vary from about 0.1 to about 10 pg/mm 2 , including about 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5,
  • the therapeutic dose density is of about 0.5 to about 5 pg/mm 2 .
  • the concentration density of the therapeutic agent in the coating layer or within the polymer microparticle may be from 0.1 pg/mm 2 to 10 pg/mm 2 , from 0.1 pg/mm 2 to 8 pg/mm 2 , from 0.1 pg/mm 2 to 6 pg/mm 2 , from 0.1 pg/mm 2 to 4 pg/mm 2 , from 0.1 pg/mm 2 to 2 pg/mm 2 , from 0.1 pg/mm 2 to 1 pg/mm 2 , from 1 pg/mm 2 to 10 pg/mm 2 , from 1 pg/mm 2 to 8 pg/mm 2 , from 1 pg/mm 2 to 6 pg/mm 2 , from 1 pg/mm 2 to 4 pg/mm 2 , from 1 pg/mm 2 to
  • the concentration density of therapeutic agent in the coating layer or polymer microparticle may be from 0.5 pg/mm 2 to 5 pg/mm 2 .
  • the methods to apply the coating layer include to a medical device may include dip coating, metering coating, spray coating, electrostatic spray coating, roller coating, spin coating, ink-jet printing, 3D printing, or combinations thereof.
  • a preferred method is metering coating and spray coating. After the solvent has evaporated, the coating layer is left on the surface.
  • the coating layer may include crystalline therapeutic agent and/or an amorphous therapeutic agent of a particular size range or ranges.
  • the crystalline and/or amorphous therapeutic agent can be embedded within the coating layer.
  • the crystalline and/or amorphous therapeutic agent is loaded within a polymer microparticle embedded in the coating layer.
  • the crystalline and/or amorphous therapeutic agent adheres to the surface of the medical device through the evaporation of a solvent.
  • the crystalline and/or amorphous therapeutic agent microparticle size can vary from about 0.1 pm to about 100 pm, including about 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 99 pm and any size or number therein.
  • the particle size is of from about 1 pm to about 20 pm. In other aspects, the particle size of from about 10 pm to about 100 pm. Size selection can be achieved through methods understood in the art, such as by passing through mesh of a pre-determined pore or hole size. The desired particle size can be achieved by dry grind, microfluidics, or wet grinding.
  • the grinding method may include techniques such as use of a jaw crusher, ultra-centrifugal mill, cyclone mill, cross beater mill, rotor beater mill, cutting mill, knife mill, mortar grinder, disc mill, mixer mill, cryomill, planetary ball mill, drum mill, and/or fine grinding rod mill.
  • the particle size may be achieved with use of a ball mill.
  • the ground drug particles and polymer mix may be combined with a solvent (or a mixture of solvents) and form a slurry coating solution.
  • the methods may also include application of the slurry coating solution to a medical device surface. Such techniques for application may include dip coating, metering coating, spray coating, electrostatic spray coating, roller coating, spin coating, ink-jet printing, and 3D printing.
  • the method includes metering coating.
  • the coating layer may include a surfactant.
  • the surfactant is provided at a mass with respect to the first solution of about 1.5 mg to about 160 mg, including about 2, 5, 10, 15, 20, 25, 50, 75, 100, 125, and 150 mg.
  • the surfactant is a polyosrbate, such as polysorbate 20, polysorbayte 80, or similar polysorbate with varying aliphatic tail lengths.
  • the surfactant is sodium stearate, sodium docusate, an alkyl ether phosphate, benzalkoaonium chloride, perfluorooctanesulfonate, combinations thereof, or similar.
  • the surfactant can be an anionic surfactant, a cationic surfactant, a non-ionic surfactant, or an amphoteric surfactant.
  • exemplary surfactants may be chosen from PEG fatty esters, PEG omega- 3 fatty esters and alcohols, glycerol fatty esters, sorbitan fatty esters, PEG glyceryl fatty esters, PEG sorbitan fatty esters, sugar fatty esters, PEG sugar esters, Tween 20, Tween 40, Tween 60, p-isononylphenoxypolyglycidol, PEG laurate, PEG oleate, PEG stearate, PEG glyceryl laurate, PEG glyceryl oleate, PEG glyceryl stearate, polyglyceryl laurate, polyglyceryl oleate, polyglyceryl myristate, polyglyceryl palmitate, polygly
  • the coating layer includes a hydrophobic polymer with the therapeutic dispersed throughout.
  • the biodegradable polymer chosen from a fatty acid, a fatty acid ester, polylactic acid (PLLA,PDLA,PDLLA), polycaprolactone (PCL), sodium docusate, PLGA, PLGA-b-mPEG, polyglutamic acid, polyacrilic acid, hyaluronic acid, alginate, PVA, PVP, Pluronic (PEO-PPO-PEO), cellulose, CMC, HPC, starch, chitosan, human serum albumin (HSA), phospholipids, fatty acid, fatty acid esters, triglycerides, beeswax, cyclodextrin, Tween 20, Tween 80, TPGS, SLS, butylated hydroxytoluene, vitamin E, vitamin E succinate, tannic acid, polyethylene glycol, N-isopropy
  • the polymer is a bioabsorbable polymer of a hydrophobic or hydrophilic nature.
  • bioabsorbable hydrophobic materials may include semi -synthetic glycerides (e.g.
  • the coating layer includes one or more excipients.
  • Suitable excipients that can be used in some aspects of the present disclosure include, without limitation, organic and inorganic pharmaceutical excipients, natural products and derivatives thereof (such as sugars, vitamins, amino acids, peptides, proteins, and fatty acids), surfactants (anionic, cationic, nonionic, and ionic), and mixtures thereof.
  • organic and inorganic pharmaceutical excipients such as sugars, vitamins, amino acids, peptides, proteins, and fatty acids
  • surfactants anionic, cationic, nonionic, and ionic
  • excipients may be useful for purposes of the present disclosure, such as polyglutamic acid, polyacrilic acid, hyaluronic acid, alginate, PVA, PVP, Pluronic (PEO-PPO-PEO), cellulose, CMC, HPC, starch, chitosan, human serum albumin (HSA), phospholipids, fatty acid, fatty acid esters, triglycerides, beeswax, cyclodextrin, polysorbates, polyethylene glycol, polyvinylpyrrolidone (PVP) and aliphatic polyesters.
  • PVP polyvinylpyrrolidone
  • the excipients may feature a drug affinity part.
  • the excipients of the present disclosure may feature a hydrophilic part.
  • hydrophilic As is understood in the art, the terms “hydrophilic” and “hydrophobic” are relative terms.
  • the excipient is a compound that includes polar or charged hydrophilic moieties as well as non-polar hydrophobic (lipophilic) moieties.
  • the hydrophilic part can accelerate diffusion and increase permeation of the therapeutic agent into tissue.
  • the hydrophilic part of the excipient may facilitate rapid movement of therapeutic agent off the expandable medical device during deployment at the target site by preventing hydrophobic drug molecules from clumping to each other and to the device, increasing drug solubility in interstitial spaces, and/or accelerating drug passage through polar head groups to the lipid bilayer of cell membranes of target tissues.
  • Exemplary excipients for application in the present disclosure may include chemical compounds with one or more hydroxyl, amino, carbonyl, carboxyl, acid, amide or ester moieties. Hydrophilic chemical compounds with one or more hydroxyl, amino, carbonyl, carboxyl, acid, amide or ester moi eties having a molecular weight less than 5,000 to 10,000 are preferred in certain aspects. In other aspects, molecular weight of the excipient with one or more hydroxyl, amino, carbonyl, carboxyl, acid, amide, or ester moi eties is preferably less than 1000 to 5,000, or more preferably less than 750 to 1,000, or most preferably less than 750. In these aspects, the molecular weight of the excipient is less than that of the therapeutic agent to be delivered.
  • the one or more excipients may be selected from amino alcohols, alcohols, amines, acids, amides and hydroxyl acids in both cyclo- and linear- aliphatic and aromatic groups.
  • examples include L-ascorbic acid and its salt, D-glucoascorbic acid and its salt, tromethamine, triethanolamine, diethanolamine, meglumine, glucamine, sodium docusate, urea, amine alcohols, glucoheptonic acid, glucomic acid, hydroxyl ketone, hydroxyl lactone, gluconolactone, glucoheptonolactone, glucooctanoic lactone, gulonic acid lactone, mannoic lactone, ribonic acid lactone, lactobionic acid, glucosamine, glutamic acid, benzyl alcohol, benzoic acid, hydroxybenzoic acid, propyl 4-hydroxybenzoate, lysine acetate salt, gentisic acid
  • Some of the chemical compounds with one or more hydroxyl, amine, carbonyl, carboxyl, amide or ester moieties described herein are very stable under heating, survive an ethylene oxide sterilization process, and/or do not react with the therapeutic agent during sterilization.
  • the one or more excipients may be selected from amino acids and salts thereof.
  • the excipient may be one or more of alanine, arginine, asparagines, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, proline, isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, tryptophan, tyrosine, valine, and derivatives thereof are.
  • low- solubility amino acid refers to amino acid having a solubility in unbuffered water of less than about 4% (40 mg/ml). These include cystine, tyrosine, tryptophan, leucine, isoleucine, phenylalanine, asparagine, aspartic acid, glutamic acid, and methionine.
  • Amino acid dimers, sugar-conjugates, and other derivatives may also be considered for excipients.
  • hydrophilic molecules may be joined to hydrophobic amino acids, or hydrophobic molecules to hydrophilic amino acids, to make additional excipients useful in aspects of the present disclosure.
  • Catecholamines such as dopamine, levodopa, carbidopa, and DOPA, are also useful as excipients.
  • the excipient may be of a material that is at a glass transition temperature at 37 °C or higher. As identified herein, providing a material on the medical device that transitions to a sticky or tacky state in situ within the vessel of the subject allows for adhering the coating to the vessel wall.
  • Such materials may include hydrogenated coconut oil, coconut oil, mineral oil, cetyl alcohol, petrolatum, petroleum jelly, decanol, soft paraffin, tridecanol, dodecanol, long chain saturated fatty acids, long chain unsaturated fatty acids, fatty acid esters, fatty acid ethers, witepsol, solid lipids, methyl stearate, triglycerides, glyceryl monostearate, glyceryl palmitostearate, stearic acid, palmitic acid, decanoic acid, behenic acid, beeswax, carnauba wax, paraffin, fatty acid triglycerides, fatty acid alcohols or combinations thereof.
  • the excipients may be liquid additives.
  • One or more liquid excipients may be can be used in the medical device coating to improve the integrity of the coating.
  • a liquid excipient can improve the compatibility of the therapeutic agent in the coating mixture.
  • the liquid excipients used in aspects of the present disclosure is not a solvent.
  • the solvents such as ethanol, methanol, dimethylsulfoxide, and acetone, will be evaporated after the coating is dried. In other words, the solvent will not stay in the coating after the coating is dried. In contrast, the liquid excipients in aspects of the present disclosure will stay in the coating after the coating is dried.
  • the liquid excipient is liquid or semi-liquid at room temperature and one atmosphere pressure.
  • the liquid excipient may form a gel at room temperature.
  • the liquid excipient may be a non-ionic surfactant.
  • liquid excipients include PEG-fatty acids and esters, PEG-oil transesterification products, polyglyceryl fatty acids and esters, Propylene glycol fatty acid esters, PEG sorbitan fatty acid esters, and PEG alkyl ethers as mentioned above.
  • Some examples of a liquid excipient are Tween 80, Tween 81, Tween 20, Tween 40, Tween 60, Solutol HS 15, Cremophor RH40, and Cremophor EL&ELP.
  • the excipient may be a surfactant; a chemical compound with one or more hydroxyl, amine, carbonyl, carboxyl, amides or ester moieties; or both.
  • exemplary surfactants may be chosen from PEG fatty esters, PEG omega-3 fatty esters and alcohols, glycerol fatty esters, sorbitan fatty esters, PEG glyceryl fatty esters, PEG sorbitan fatty esters, sugar fatty esters, PEG sugar esters, Tween 20, Tween 40, Tween 60, p-isononylphenoxypolyglycidol, PEG laurate, PEG oleate, PEG stearate, PEG glyceryl laurate, PEG glyceryl oleate, PEG glyceryl stearate, polyglyceryl laurate, polyglyceryl oleate, polyglyceryl myristate, poly
  • one or more of a surfactant or a small water-soluble molecule (the chemical compounds with one or more hydroxyl, amine, carbonyl, carboxyl, amides or ester moieties) with the therapeutic agent are in certain cases superior to only utilizing the therapeutic agent and a single excipient.
  • the drug coating may have increased stability during transit and rapid drug release when pressed against tissues of the lumen wall at the target site of therapeutic intervention when compared to some formulations comprising the therapeutic agent and only one excipient.
  • the miscibility and compatibility of the therapeutic agent with the excipient or the drug coating with the medical device generally, is improved by the presence of the one or more additional excipients.
  • a surfactant may allow for improved coating uniformity and integrity.
  • the coating layer(s) may include multiple excipients, and one excipient is more hydrophilic than one or more of the other excipients.
  • the coating layer multiple excipients, and one excipient has a different structure from that of one or more of the other excipients.
  • the coating layer includes multiple excipients.
  • Some aspects of the present disclosure may include a mixture of at least two additional excipients, for example, a combination of one or more surfactants and one or more chemical compound with one or more hydroxyl, amine, carbonyl, carboxyl, amides or ester moi eties.
  • therapeutic agents may bind to extremely water-soluble small molecules more poorly than surfactants, which can lead to suboptimal coating uniformity and integrity.
  • Some surfactants may adhere so strongly to the therapeutic agents and the surface of the medical device that the therapeutic agent is not able to rapidly release from the surface of the medical device at the target site.
  • some water-soluble small molecules adhere so poorly to the medical device that they release therapeutic agents before it reaches the target site, for example, into serum during the transit of a coated balloon catheter to the site targeted for intervention.
  • the coating layer may have improved properties over a formulation with only one excipient or no excipient.
  • the one or more additional excipients may include an antioxidant.
  • An antioxidant is a molecule capable of slowing or preventing the oxidation of other molecules. Oxidation reactions can produce free radicals and/or peroxides, which start chain reactions and may cause degradation of therapeutic agents. Antioxidants terminate these chain reactions by removing free radicals and inhibiting oxidation of the active agent by being oxidized themselves. Antioxidants are used as the one or more additional excipients in certain aspects to prevent or slow the oxidation of the therapeutic agents in the coatings for medical devices. Antioxidants are a type of free radical scavengers.
  • the antioxidant may be used alone or in combination with other additional excipients in certain aspects and may prevent degradation of the active therapeutic agent during sterilization or storage prior to use.
  • Some representative examples of antioxidants that may be used in the drug coatings of the present disclosure include, without limitation, oligomeric or polymeric proanthocyanidins, polyphenols, polyphosphates, polyazomethine, high sulfate agar oligomers, chitooligosaccharides obtained by partial chitosan hydrolysis, polyfunctional oligomeric thioethers with sterically hindered phenols, hindered amines such as, without limitation, p-phenylene diamine, trimethyl dihydroquinolones, and alkylated diphenyl amines, substituted phenolic compounds with one or more bulky functional groups (hindered phenols) such as tertiary butyl, arylamines, phosphites, hydroxylamines, and benzofuranones.
  • aromatic amines such as p-phenylenediamine, diphenylamine, and N,N' disubstituted p- phenylene diamines may be utilized as free radical scavengers.
  • BHT butylated hydroxytoluene
  • BHA butylated hydroxyanisole
  • L-ascorbate L-ascorbate
  • Vitamin E herbal rosemary, sage extracts, glutathione, resveratrol, ethoxyquin, rosmanol, isorosmanol, rosmaridiphenol, propyl gallate, gallic acid, caffeic acid, p-coumeric acid, p-hydroxy benzoic acid, astaxanthin, ferulic acid, dehydrozingerone, chlorogenic acid, ellagic acid, propyl paraben, sinapic acid, daidzin, glycitin, genistin, daidzein, g
  • phosphites examples include di(stearyl)pentaerythritol diphosphite, tris(2,4-di-tert.butyl phenyl)phosphite, dilauryl thiodipropionate and bis(2,4-di-tert.butyl phenyl)pentaerythritol diphosphite.
  • hindered phenols include octadecyl-3, 5, di-tert.butyl-4-hydroxy cinnamate, tetrakis-methylene-3-(3',5'-di-tert.butyl-4-hydroxyphenyl)propionate methane 2,5-di-tert- butylhydroquinone, ionol, pyrogallol, retinol, and octadecyl-3-(3,5-di-tert.butyl-4- hydroxyphenyl)propionate.
  • An antioxidant may include glutathione, lipoic acid, melatonin, tocopherols, tocotrienols, thiols, Beta- carotene, retinoic acid, cryptoxanthin, 2,6-di-tert- butylphenol, propyl gallate, catechin, catechin gallate, and quercetin.
  • Preferable antioxidants are butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA).
  • the present disclosure concerns methods of using the scoping device as disclosed herein.
  • the methods can include inserting the scoping device into a space within a subject.
  • the space is a subject’s airways.
  • the presence of a camera on the distal end allows a user to view and/or nhavigate the subject’s space as the scoping section is moved further therein.
  • the methods include identifying a target tissue within the space of the subject.
  • the methods may also include expanding and/or inflating the balloon in situ of a subject, such as ay a site of interest or site in need of treatment. Once inflated, the coating layer may be deposited on the site of interest or need. For example, providing a pharmaceutical or therapeutic agent in the coating layer can allow for such to be deposited on the surface of the target tissue, thereby applying directly treatment thereto.
  • the cables connected to the exterior of the inflatable balloon allow a user to cause the balloon to move or rotate in situ. For example, as set forth in FIG. 5, pulling the cable on one side of the balloon can increase the surface area contact between the inflated balloon and the target tissue. It will also be appreciated that in some aspects, the pressure within the balloon or the degree of inflation therein may allow a user to increase the surface contact area. By way of example, once a balloon is in a preferred position, allowing the balloon to partially deflate may cause the balloon to drape over the site for delivery. In some aspects, providing multiple cables to the exterior surface of the balloon allows a user to move or rotate the inflated balloon in two or more directions, thereby increasing the surface area upon which the coating layer is deposited.
  • Patents, applications, and publications mentioned in the specification are indicative of the levels of those skilled in the art to which the invention pertains. These patents and publications are incorporated herein by reference to the same extent as if each individual application or publication was specifically and individually incorporated herein by reference.

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Abstract

La présente divulgation concerne un dispositif endoscopique équipé d'un ballonnet gonflable. Un ou plusieurs câbles reliés à l'extérieur du ballonnet sont filetés à travers au moins une partie du dispositif endoscopique et sont disponibles pour permettre à un utilisateur d'appliquer une force de traction sur ceux-ci. Une telle force peut ensuite permettre au ballonnet de tourner ou de se déplacer à travers une zone souhaitée de tissu à l'intérieur d'un sujet. La présence d'une couche de revêtement sur l'extérieur du ballonnet permet d'administrer celle-ci à un site spécifique. Le présent dispositif permet donc l'administration à un site spécifique d'un ou de plusieurs agents thérapeutiques par l'intermédiaire d'un dispositif endoscopique.
PCT/US2023/084799 2023-12-19 2023-12-19 Ballonnet revêtu de médicament endobronchique Pending WO2025136359A1 (fr)

Priority Applications (1)

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PCT/US2023/084799 WO2025136359A1 (fr) 2023-12-19 2023-12-19 Ballonnet revêtu de médicament endobronchique

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200069920A1 (en) * 2016-03-15 2020-03-05 Medtronic Holding Company Sàrl Devices for delivering a chemical denervation agent and methods of use
US20210001099A1 (en) * 2008-06-02 2021-01-07 Loma Vista Medical, Inc. Inflatable medical devices
US20210162185A1 (en) * 2019-12-03 2021-06-03 Boston Scientific Scimed, Inc. Medical delivery device and method of use
US20230149672A1 (en) * 2019-02-22 2023-05-18 Urotronic, Inc. Drug-coated balloon catheters for body lumens

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210001099A1 (en) * 2008-06-02 2021-01-07 Loma Vista Medical, Inc. Inflatable medical devices
US20200069920A1 (en) * 2016-03-15 2020-03-05 Medtronic Holding Company Sàrl Devices for delivering a chemical denervation agent and methods of use
US20230149672A1 (en) * 2019-02-22 2023-05-18 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US20210162185A1 (en) * 2019-12-03 2021-06-03 Boston Scientific Scimed, Inc. Medical delivery device and method of use

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