Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use

Methods of preventing adhesion between issues are provided that utilizes in situ crosslinked biomaterials. The biomaterial contains at least the crosslinked product of two biocompatible, non-immunogenic components having reactive groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. Exemplary uses for the crosslinked compositions include preventing adhesions following surgery or injury, and preventing scar tissue formation.

COMPOSITIONS AND SYSTEMS FOR FORMING CROSSLINKED BIOMATERIALS AND ASSOCIATED METHODS OF PREPARATION AND USE

Kits comprising dry power compositions are provided that readily crosslink in situ to provide crosslinked biomaterials. The dry powder composition contains at least two biocompatible, non-immunogenic components having reactive groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. Exemplary uses for the crosslinked biomaterials include tissue augmentation, biologically active agent delivery, bioadhesion, and prevention of adhesions following surgery or injury. 1. A kit for use in for use in medical applications , comprising: i. a first component having a first hydrophilic polymer core substituted with m thiol groups, where m≧2', {'sub': 3', '2', '2', '2', '3', '2', '5', '4', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'ii. a second component having a second hydrophilic polymer core substituted with n electrophilic groups, where n≧2 and m+n>4, and wherein the electrophilic group is independently —CO—Cl, —(CO)—O—(CO)—R (where R is an alkyl group), —CH═CH—CH═O and —CH═CH—C(CH)═O, halo, —N═C═O, —N═C═S, —SOCH═CH, —O(CO)—C═CH, —O(CO)—C(CH)═CH, —S—S—(CHN), —O(CO)—C(CHCH)═CH, —CH═CH—C═NH, —COOH, —(CO)O—N(COCH), —O—(CO)—O—N(COCH), —CHO, —(CO)O—N(COCH)—S(O)OH, and —N(COCH).'}], '(a) a dry powder composition comprising'}(b) a first solution having a pH within the range of about 2.1-2.3; and(c) a second solution having a pH within the range of about 6.0 to 11.0,wherein the thiol group and the electrophilic groups are non-reactive in a dry environment, and wherein each of (a), (b) and (c) is packaged separately and admixed immediately prior to use.2. The kit of claim 1 , wherein prior to use claim 1 , each component is in a separate sterile package.3. The kit of claim 1 , further comprising a delivery device.4. The kit of claim 3 , wherein the delivery device is a multi-component spray device.5. The kit of claim 4 , wherein the multi-component spray device is a multiple-compartment syringe system ...

Modified hyaluronic acid polymer compositions and related methods

The present application provides compositions comprising hyaluronic acid having low levels of functional group modification, mixtures formed by controlled reaction of such lightly modified hyaluronic acid with suitable difunctional or multi-functional crosslinkers, and hydrogel precursor compositions and the resulting hydrogels. The compositions are lightly cross-linked and possess low pro-inflammatory properties when injected in vivo, and can be used as, for example, medical devices, biomedical adhesives and sealants, and for localized delivery of bioactive agents, among other uses.

Drug delivery from rapid gelling polymer composition

Compositions are disclosed that afford drug delivery from two-part polymer compositions that rapidly form covalent linkages when mixed together. Such compositions are particularly well suited for use in a variety of tissue related applications when rapid adhesion to the tissue and gel formation is desired along with drug delivery. For example, the compositions are useful as tissue sealants, in promoting hemostasis, in effecting tissue adhesion, in providing tissue augmentation, and in the prevention of surgical adhesions.

Multifunctional compounds for forming crosslinked biomaterials and methods of preparation and use

Multifunctional compounds are provided that readily crosslink in situ to provide crosslinked biomaterials. The multifunctional compounds contain a single component having at least three reactive functional groups thereon, with the functional groups selected so as to be non-reactive in an initial environment and inter-reactive in a modified environment. Reaction of a plurality of the multifunctional compounds results in a three-dimensional crosslinked matrix. In one embodiment, a first functional group is nucleophilic, a second functional group is electrophilic, and at least one additional functional group is nucleophilic or electrophilic. Methods for preparing and using the multifunctional compounds, and kits including the multifunctional compounds are also provided. Exemplary uses for the multifunctional compounds include tissue augmentation, biologically active agent delivery, bioadhesion, and prevention of adhesions following surgery or injury.

COMPOSITIONS AND METHODS FOR COATING MEDICAL IMPLANTS

Medical implants are provided which release a fluoropyrimidine or an analog thereof, thereby inhibiting or reducing the incidence of infection associated with the implant. 1. A medical implant which releases a fluoropyrimidine.2. The medical implant according to wherein said implant is covered or coated in whole or in part with a composition comprising a fluoropyrimidine or an analog thereof.3. The medical implant according to wherein said fluoropyrimidine is 5-fluorouracil.4. The medical implant according to wherein said composition further comprises a polymer.5. The medical implant according to wherein said polymer is a non-biodegradable polymer.6. The medical implant according to wherein said polymer is a polyurethane claim 4 , cellulose or a cellulose-derived polymer claim 4 , or a combination of polyurethane and cellulose or a cellulose-derived polymer.7. The medical implant according to wherein said fluoropyrimidine is 5-fluorouracil.8. The medical implant according to wherein said medical implant is a vascular catheter or a dialysis catheter.9. A composition claim 1 , comprising one or more polymers and a fluoropyrimidine claim 1 , wherein the composition is in the form of a coating on a medical implant claim 1 , and wherein the coated medical implant releases the fluoropyrimidine in an amount effective in reducing or inhibiting bacterial infection in an in vitro radial diffusion assay.10. The composition according to wherein the one or more polymers comprises a non-biodegradable polymer.11. The composition according to wherein the one or more polymers comprise a a polyurethane claim 10 , cellulose or a cellulose-derived polymer claim 10 , or a combination of polyurethane and cellulose or a cellulose-derived polymer.12. The composition according to wherein the fluoropyrimidine is 5-fluorouracil.13. (canceled)14. (canceled)15. A method for making a medical implant claim 9 , comprising covering or coating a medical implant with a fluoropyrimidine or an analog ...

COMPOSITIONS AND METHODS FOR COATING MEDICAL IMPLANTS

Medical implants are provided which release an anthracycline, fluoropyrimidine, folic acid antagonist, podophylotoxin, camptothecin, hydroxyurea, and/or platinum complex, thereby inhibiting or reducing the incidence of infection associated with the implant. 112-. (canceled)13. A composition , comprising a polymer and a fluoropyrimidine , wherein said fluoropyrimidine is present in said composition at a concentration of less than 10M.14. The composition according to wherein said fluoropyrimidine is present in said composition at a concentration of less than any one of 10M claim 13 , 10M claim 13 , or 10M.15. The composition according to wherein said polymer is a non-biodegradable polymer.16. The composition according to wherein said polymer is a polyurethane.17. The composition according to wherein said polymer is a poly(lactide-co-glycolide).18. The composition according to wherein said fluoropyrimidine is 5-fluorouracil.19. A method for reducing or inhibiting infection associated with a medical implant claim 13 , comprising the step of introducing into a patient a medical implant which has been covered or coated with a fluoropyrimidine.20. The method according to wherein said fluoropyrimidine is 5-fluorouracil.21. A method for making medical implants claim 19 , comprising covering or coating a medical implant with a fluoropyrimidine.22. The method according to wherein said fluoropyrimidine is 5-fluorouracil.23. The method according to wherein said medical implant covered or coated by dipping or by impregnation. This application is a continuation of U.S. patent application Ser. No. 11/343,714, filed Jan. 31, 2006, which is a continuation of U.S. patent application Ser. No. 10/447,309, filed May 27, 2003, now abandoned, which claims benefit under 35 U.S.C. §119(e) of U.S. Provisional Application Ser. No. 60/383,419, filed May 24, 2002, which applications are incorporated herein by reference in their entirety.1. Field of the InventionThe present invention relates ...

Multifunctional compounds for forming crosslinked biomaterials and methods of preparation and use

Multifunctional compounds are provided that readily crosslink in situ to provide crosslinked biomaterials. The multifunctional compounds contain a single component having at least three reactive functional groups thereon, with the functional groups selected so as to be non-reactive in an initial environment and inter-reactive in a modified environment. Reaction of a plurality of the multifunctional compounds results in a three-dimensional crosslinked matrix. In one embodiment, a first functional group is nucleophilic, a second functional group is electrophilic, and at least one additional functional group is nucleophilic or electrophilic. Methods for preparing and using the multifunctional compounds, and kits including the multifunctional compounds are also provided. Exemplary uses for the multifunctional compounds include tissue augmentation, biologically active agent delivery, bioadhesion, and prevention of adhesions following surgery or injury.

IN-SITU GEL FORMING COMPOSITIONS

The present application provides rapid-gelling, sprayable hyaluronic-acid based compositions, kits, related methods, precursor formulations, and uses thereof. 1. A kit comprising:(i) a first container comprising an aqueous solution of vinyl sulfone-derivatized hyaluronic acid (“HA-VS”) at a concentration of from about 10-300 mg/mL, where HA-VS is (2-(vinylsulfonyl)ethoxy)hyaluronic acid, and the HA-VS has from about 2%-70% of its hydroxyl groups transformed to 2-(vinylsulfonyl)ethoxy groups,(ii) a second container comprising a thiol-functionalized polyethylene glycol having from 2 to 8 thiol groups, and(iii) a third container comprising a 30-1000 mM buffer solution at a pH ranging from about 7-12, in an amount effective, when mixed with the contents of the first and second containers, to provide a solution having a HA-VS concentration of 2-8% (w/v) and a thiol-functionalized polyethylene glycol concentration of 2-8% (w/v),wherein the components of the first, second and third containers, when combined, are effective to form a gel within from about 5 seconds to 1 hour of mixing.2. A liquid composition formed from the combination of (i) an aqueous solution of vinyl sulfone-derivatized hyaluronic acid (“HA-VS”) at a concentration of from about 10-300 mg/mL , where HA-VS is (2-(vinylsulfonyl)ethoxy)hyaluronic acid , and the HA-VS has from about 2%-70% of its hydroxyl groups transformed to 2-(vinylsulfonyl)ethoxy groups , (ii) a thiol-functionalized polyethylene glycol having from 2 to 8 thiol groups , and (iii) a 30-1000 mM buffer solution at a pH ranging from about 7-12 ,where the concentration of the thiol-functionalized polyethylene glycol in the liquid composition ranges from about 4-300 mg/mL, andthe liquid composition is effective to form a gel within from about 5 seconds to about 1 hour of mixing components (i), (ii) and (iii).3. The kit of claim 1 , wherein the vinyl sulfone-derivatized hyaluronic acid has from about 7%-35% claim 1 , or from 10% to 25% claim 1 , ...

Modified Hyaluronic Acid Polymer Compositions and Related Methods

The present application provides compositions comprising hyaluronic acid having low levels of functional group modification, mixtures formed by controlled reaction of such lightly modified hyaluronic acid with suitable difunctional or multi-functional crosslinkers, and hydrogel precursor compositions and the resulting hydrogels. The compositions are lightly cross-linked and possess low pro-inflammatory properties when injected in vivo, and can be used as, for example, medical devices, biomedical adhesives and sealants, and for localized delivery of bioactive agents, among other uses. 149.-. (canceled)50. A method of treating a mammalian subject having osteoarthritis , comprising administering a therapeutically effective amount of a hydrogel composition into an intra-articular space of a joint of the subject , the hydrogel composition comprising crosslinked hydrogel particles comprising triamcinolone or a pharmaceutically acceptable salt thereof in an aqueous solution comprising hyaluronic acid , wherein the crosslinked hydrogel particles are formed by reaction of polyethylene glycol dithiol with 2-(vinylsulfonyl)ethoxy-derivatized hyaluronic acid having from 1-10% of its hydroxyl groups derivatized with 2-(vinylsulfonyl)ethoxy groups.51. The method of claim 50 , wherein the polyethylene glycol dithiol has a molecular weight in a range of about 250 to about 20 claim 50 ,000 daltons.52. The method of claim 51 , wherein the triamcinolone is in the form of a pharmaceutically acceptable salt.53. The method of claim 52 , wherein the triamcinolone salt is triamcinolone acetonide.54. The method of claim 53 , wherein the hydrogel composition comprises from about 0.01 to about 3 percent by weight triamcinolone acetonide.55. The method of claim 54 , wherein the hydrogel composition comprises from about 0.1 to about 2 percent by weight triamcinolone acetonide.56. The method of claim 55 , wherein the crosslinked hydrogel particles have diameter sizes ranging from about 0.10 to 3 ...

MODIFIED HYALURONIC ACID POLYMER COMPOSITIONS AND RELATED METHODS

The present application provides compositions comprising hyaluronic acid having low levels of functional group modification, mixtures formed by controlled reaction of such lightly modified hyaluronic acid with suitable difunctional or multi-functional crosslinkers, and hydrogel precursor compositions and the resulting hydrogels. The compositions are lightly cross-linked and possess low pro-inflammatory properties when injected in vivo, and can be used as, for example, medical devices, biomedical adhesives and sealants, and for localized delivery of bioactive agents, among other uses. 1. A hydrogel formed by reaction of a hyaluronic acid having from 10% or less of its hydroxyl groups derivatized by reaction with divinyl sulfone (“2-(vinylsulfonyl)ethoxy)hyaluronic acid”) with a thiol crosslinker having from two to eight thiol groups.2. (canceled)3. The hydrogel of claim 1 , where the hyaluronic acid has a degree of conversion of hydroxyl groups to 2-(vinylsulfonyl)ethoxy groups of about 4-5% per disaccharide repeat unit.4. The hydrogel of claim 1 , wherein at least one of:the hyaluronic acid has an average molecular weight ranging from 700 to 3 million daltons, andthe thiol-functionalized polyethylene glycol possesses a molecular weight ranging from about 250 to about 20,000 daltons.5. (canceled)6. The hydrogel of claim 1 , where the thiol crosslinker is a thiol-functionalized polyethylene glycol.7. (canceled)8. The hydrogel of claim 4 , where the thiol-functionalized polyethylene glycol is polyethylene glycol dithiol (PEG dithiol).9. The hydrogel of claim 6 , where the thiol-functionalized polyethylene glycol possesses a polyol core selected from glycerol claim 6 , glycerol dimer (3 claim 6 ,3′-oxydipropane-1 claim 6 ,2-diol) trimethylolpropane claim 6 , sorbitol claim 6 , pentaerythritol claim 6 , and hexaglycerol.10. The hydrogel of claim 9 , where the thiol-functionalized polyethylene glycol is four-armed and possesses a pentaerythritol core.11. (canceled)12. The ...

COMPOSITIONS AND METHODS FOR COATING MEDICAL IMPLANTS

Medical implants are provided which release a fluoropyrimidine or an analog thereof, thereby inhibiting or reducing the incidence of infection associated with the implant. 117-. (canceled)18. A medical device having a reduced likelihood of infection , the device comprising a medical implant which has been covered or coated with an antimicrobially effective amount of a fluoropyrimidine or an analog thereof.19. The device of claim 18 , where the implant is coated or covered with an antimicrobially effective amount of a fluoropyrimidine.20. The device of claim 19 , wherein said fluoropyrimidine is 5-fluorouracil.21. The device of claim 18 , comprising 0.1 μg to 1 mg fluoropyrimidine per cmof surface area of the portion of the medical implant to which the fluoropyrimidine has been applied.22. The device of claim 21 , wherein the implant releases the fluoropyrimidine in an amount effective to reduce or inhibit the likelihood of infection associated with the implantation of the device in a subject.23. The device of claim 22 , wherein the implant does not release the fluoropyrimidine in an amount effective for the treatment of cancer in the subject that receives the implant.24. The device of claim 18 , further comprising a polymer coating in combination with the fluoropyrimidine or analog thereof.25. The device of claim 24 , wherein the polymer coating comprises polyurethane.26. The device of claim 18 , wherein the implant is a catheter.27. The device of claim 26 , wherein the catheter is a dialysis catheter.28. The device of claim 18 , which is not useful for treating cancer. This application is a continuation of U.S. patent application Ser. No. 13/663,254, filed Oct. 29, 2012, now pending, which is a continuation of U.S. patent application Ser. No. 12/107,629, filed Apr. 22, 2008, now U.S. Pat. No. 8,313,760, which is a continuation-in-part of U.S. patent application Ser. No. 10/447,309, filed May 27, 2003, now abandoned, which claims the benefit under 35 U.S.C. §119(e) ...

MODIFIED HYALURONIC ACID POLYMER COMPOSITIONS AND RELATED METHODS

The present application provides compositions comprising hyaluronic acid having low levels of functional group modification, mixtures formed by controlled reaction of such lightly modified hyaluronic acid with suitable difunctional or multi-functional crosslinkers, and hydrogel precursor compositions and the resulting hydrogels. The compositions are lightly cross-linked and possess low pro-inflammatory properties when injected in vivo, and can be used as, for example, medical devices, biomedical adhesives and sealants, and for localized delivery of bioactive agents, among other uses. 1. A hydrogel formed by reaction of a hyaluronic acid having from 1-10% of its hydroxyl groups derivatized by reaction with divinyl sulfone (“2-(vinylsulfonyl)ethoxy)hyaluronic acid”) with a thiol crosslinker having from two to eight thiol groups.2. The hydrogel of claim 1 , where the hyaluronic acid has a degree of conversion of hydroxyl groups to 2-(vinylsulfonyl)ethoxy groups selected from 1% claim 1 , 2% claim 1 , 3% claim 1 , 4% claim 1 , 5% claim 1 , 6% claim 1 , 7% claim 1 , 8% claim 1 , 9% claim 1 , and 10%.3. The hydrogel of claim 2 , where the hyaluronic acid has a degree of conversion of hydroxyl groups to 2-(vinylsulfonyl)ethoxy groups of about 4-5% per disaccharide repeat unit.43. The hydrogel of any one of - claims 1 , wherein the hyaluronic acid has an average molecular weight ranging from 700 to 3 million daltons.54. The hydrogel of any one of - claims 1 , where the thiol crosslinker possesses a number of thiol groups selected from 2 claims 1 , 3 claims 1 , 4 claims 1 , 5 claims 1 , 6 claims 1 , 7 claims 1 , and 8.6. The hydrogel of claim 5 , where the thiol crosslinker is a thiol-functionalized polyethylene glycol.7. The hydrogel of claim 6 , where the thiol-functionalized polyethylene glycol possesses a molecular weight ranging from about 250 to about 20 claim 6 ,000 daltons.8. The hydrogel of claim 7 , where the thiol-functionalized polyethylene glycol is polyethylene ...

Rapid In-situ Gel Forming Compositions Prepared via Reaction of Vinyl Sulfone Derivatized Hyaluronic Acid with Thiol Derivatized Polyethylene Glycol at Alkaline pH

The present application provides rapid-gelling, sprayable hyaluronic-acid based compositions, kits, related methods, precursor formulations, and uses thereof. 1. A kit comprising:(i) a first container comprising an aqueous solution of vinyl sulfone-derivatized hyaluronic acid (“HA-VS”) at a concentration of from about 10-300 mg/mL, where HA-VS is (2-(vinylsulfonyl)ethoxy)hyaluronic acid, and the HA-VS has from about 2%-70% of its hydroxyl groups transformed to 2-(vinylsulfonyl)ethoxy groups,(ii) a second container comprising a thiol-functionalized polyethylene glycol having from 2 to 8 thiol groups, and(iii) a third container comprising a 30-1000 mM buffer solution at a pH ranging from about 7-12, in an amount effective, when mixed with the contents of the first and second containers, to provide a solution having a HA-VS concentration of 2-8% (w/v) and a thiol-functionalized polyethylene glycol concentration of 2-8% (w/v),wherein the components of the first, second and third containers, when combined, are effective to form a gel within from about 5 seconds to 1 hour of mixing.2. A liquid composition formed from the combination of (i) an aqueous solution of vinyl sulfone-derivatized hyaluronic acid (“HA-VS”) at a concentration of from about 10-300 mg/mL , where where HA-VS is (2-(vinylsulfonyl)ethoxy)hyaluronic acid , and the HA-VS has from about 2%-70% of its hydroxyl groups transformed to 2-(vinylsulfonyl)ethoxy groups , (ii) a thiol-functionalized polyethylene glycol having from 2 to 8 thiol groups , and (iii) a 30-1000 mM buffer solution at a pH ranging from about 7-12 ,where the concentration of the thiol-functionalized polyethylene glycol in the liquid composition ranges from about 4-300 mg/mL, andthe liquid composition is effective to form a gel within from about 5 seconds to about 1 hour of mixing components (i), (ii) and (iii).3. The kit of claim 1 , wherein the vinyl sulfone-derivatized hyaluronic acid has from about 7%-35% claim 1 , of its hydroxyl groups ...

STABILIZED COMPOSITIONS COMPRISING HYALURONIC ACID

Provided herein are hyaluronic-acid based compositions comprising a hyaluronic acid-based polymer and a corticosteroid in the presence of a stabilizing amount of one or more stabilizing additives and related methods. The resulting compositions substantially retain their viscoelastic and related rheolotical properties under conditions of storage, processing, and use. 1. A method for stabilizing a hyaluronic acid-based polymer composition against a reduction in viscosity over time , the method comprisingincorporating into an aqueous composition comprising a hyaluronic acid polymer and a corticosteroid, a stabilizing amount of a stabilizing additive selected from the group consisting of sugars, sugar alcohols, polyols and polyol-containing surfactants, to thereby provide a composition that exhibits a reduction in viscosity of no more than about 50% in comparison to its initial value when stored at 60° C. for a period of 6 days.2. A method for diminishing a reduction in viscosity over time of a hyaluronic acid-based polymer composition comprising a corticosteroid , the method comprisingincorporating into an aqueous composition comprising a hyaluronic acid polymer and a corticosteroid, a stabilizing amount of a stabilizing additive selected from the group consisting of sugars, sugar alcohols, polyols and polyol-containing surfactants, to thereby provide a composition having a stabilization ratio of greater than 1.2,wherein the stabilization ratio is the ratio of the percent retention of viscosity for the hyaluronic acid polymer-corticosteroid composition comprising the stabilizing additive to the percent retention of viscosity of the hyaluronic acid polymer-corticosteroid composition absent the stabilizing additive, when measured at a certain time point and under a defined set of storage conditions.3. The method of claim 1 , wherein the incorporating step comprises incorporating the stabilizing additive into an aqueous composition comprising the hyaluronic acid polymer ...

Block copolymer compositions and uses thereof

The present invention describes compositions, devices, and methods for the production, use and administration of the composition having a non-thermoreversible block copolymer composition.

Block copolymer compositions and uses thereof

The present invention describes compositions, devices, and methods for the production, use and administration of the composition having a non-thermoreversible block copolymer composition.

Block copolymer compositions and uses thereof

Block copolymer compositions and uses thereof

The present invention describes compositions, devices, and methods for the production, use and administration of the composition having a non-thermoreversible block copolymer composition.

Block Copolymer Compositions and Uses Thereof

The present invention describes compositions, devices, and methods for the production, use and administration of the composition having a non-thermoreversible block copolymer composition.

Block copolymer compositions and uses thereof

The present invention describes compositions, devices, and methods for the production, use and administration of the composition having a non-thermoreversible block copolymer composition.

Compositions comprising an anti-microtubule agent and a polypeptide or a polysaccharide and the use thereof for the preparation of a medicament for the treatment of inflammatory conditions

Disclosed herein are compositions and methods for treating a variety of inflammatory conditions (e.g., inflammatory arthritis, adhesions, tumor excision sites, and fibroproliferative diseases of the eye). For example, there is provided a composition comprising a protein or polysaccharide containing dispersed (e.g., in micelle or liposome form) anti-microtubule agent, which may be formulated for administration to a patient in need thereof.

Drug delivery from rapid gelling polymer composition

Medical implants and fibrosis-inducing agents

Electrical devices and anti-scarring agents

Electrical devices (e.g., cardiac rhythm management and neurostimulation devices) for contact with tissue are used in combination with an anti-scarring agent (e.g., a cell cycle inhibitor) in order to inhibit scarring that may otherwise occur when the devices are implanted within an animal.

Compositions and methods for treating contracture

A method for treating contracture is provided that includes administering to a patient in need thereof a composition that includes a therapeutic agent effective in treating contracture. Compositions, devices, and kits for use in treating contracture are also described.

Antimicrobial needle coating for extended infusion

The present invention relates to bioerodable polymeric coatings with antimicrobial agents that provide coated surfaces that resist protein absorption and infectious formation on coated surfaces of medical devices that are inserted or implanted in patients, and kits thereof with an antimicrobial disc.

Drug delivery from rapid gelling polymer composition

Compositions are disclosed that afford drug delivery from two-part polymer compositions that rapidly form covalent linkages when mixed together. Such compositions are particularly well suited for use in a variety of tissue related applications when rapid adhesion to the tissue and gel formation is desired along with drug delivery. For example, the compositions are useful as tissue sealants, in promoting hemostasis, in effecting tissue adhesion, in providing tissue augmentation, and in prevention of surgical adhesions.

Compositions and methods for coating medical implants

Compositions and methods for coating medical implants

Medical implants are provided which release a fluoropyrimidine or an analog thereof, thereby inhibiting or reducing the incidence of infection associated with the implant.

Tissue reactive compounds and compositions and uses thereof

A composition comprising a synthetic polymer, optionally in the presence of a drug, where the polymer comprises multiple activated groups. The multiple activated groups are reactive with functinality present on animal tissue, so that upon administration of the polymer to the tissue, the polymer binds to the tissue. Alternatively, the multiple activated groups are reactive with functionality present on a non-living surface, where the polymer binds to this surface to, e.g., increase the lubricity of the surface. When drug is present in the composition, the drug is then delivered to the site of polymer attachment.

Compositions and methods using hyaluronic acid and hyluronidase inhibitors

Compositions and devices including hyaluronic acid and a compound that inhibits degradation of hyaluronic acid, and methods of making and using same.

modified polymeric compositions of hyaluronic acid and related methods.

Anastomotic connector devices

Anastomotic connector devices are provided which release a therapeutic agent. The therapeutic agent may be an anti­-scarring agent that inhibits stenosis caused by the presence of the anastomotic connector device.

Compositions and methods for coating medical implants

Medical implants are provided which release an anthracycline, fluoropyrimidine, folic acid antagonist, podophylotoxin, camptothecin, hydroxyurea, and/or platinum complex, thereby inhibiting or reducing the incidence of infection associated with the implant.

Modified hyaluronic acid polymer compositions and related methods

The present application provides compositions comprising hyaluronic acid having low levels of functional group modification, mixtures formed by controlled reaction of such lightly modified hyaluronic acid with suitable difunctional or multi-functional crosslinkers, and hydrogel precursor compositions and the resulting hydrogels. The compositions are lightly cross-linked and possess low pro-inflammatory properties when injected in vivo, and can be used as, for example, medical devices, biomedical adhesives and sealants, and for localized delivery of bioactive agents, among other uses.

Stabilized compositions comprising hyaluronic acid

Provided herein are hyaluronic-acid based compositions comprising a hyaluronic acid-based polymer and a corticosteroid in the presence of a stabilizing amount of one or more stabilizing additives and related methods. The resulting compositions substantially retain their viscoelastic and related rheolotical properties under conditions of storage, processing, and use.

Polymer compositions and methods for their use

Published without an Abstract

Drug delivery from rapid gelling polymer composition

Compositions are disclosed that afford drug delivery from two-part polymer compositions that rapidly form covalent linkages when mixed together. Such compositions are particularly well suited for use in a variety of tissue related applications when rapid adhesion to the tissue and gel formation is desired along with drug delivery. For example, the compositions are useful as tissue sealants, in promoting hemostasis, in effecting tissue adhesion, in providing tissue augmentation, and in the prevention of surgical adhesions.

Modified hyaluronic acid polymer compositions and related methods

Electrical devices, anti-scarring agents, and therapeutic compositions

Electrical devices (e.g., cardiac rhythm management and neurostimulation devices) for contact with tissue are used in combination with an anti-scarring agent in order to inhibit scarring that may otherwise occur when the devices are implanted within an animal

Intravascular devices and fibrosis-inducing agents

Published without an Abstract

Drug delivery from rapid gelling polymer composition

Compositions are disclosed that afford drug delivery from two-part polymer compositions that rapidly form covalent linkages when mixed together. Such compositions are particularly well suited for use in a variety of tissue related applications when rapid adhesion to the tissue and gel formation is desired along with drug delivery. For example, the compositions are useful as tissue sealants, in promoting hemostasis, in effecting tissue adhesion, in providing tissue augmentation, and in prevention of surgical adhesions.

Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use

Crosslinkable compositions are provided that readily crosslink in situ to provide crosslinked biomaterials. The composition contains at least two biocompatible, non-immunogenic components having reactive groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. In one embodiment, a first component has nucleophilic groups and a second component has electrophilic groups. Additional components may have nucleophilic or electrophilic groups. Methods for preparing and using the compositions are also provided as are kits for delivery of the compositions. Exemplary uses for the crosslinked compositions include tissue augmentation, biologically active agent delivery, bioadhesion, and prevention of adhesions following surgery or injury.

Anastomotic connector devices

Anastomotic connector devices are provided which release a therapeutic agent. The therapeutic agent may be an anti~-scarring agent that inhibits stenosis caused by the presence of the anastomotic connector device.

Compositions and methods for coating medical implants

Drug delivery from rapid gelling polymer composition

Compositions and methods for treating contracture

A method for treating contracture is provided that includes administering to a patient in need thereof a composition that includes a therapeutic agent effective in treating contracture. Compositions, devices, and kits for use in treating contracture are also described.

Compositions and systems for forming crosslinked biomaterials and related methods of preparation and use

Compositions comprsing collagen, a second polymer and a tissue inhibitor of matrix metalloproteinase (TIMP), methods of making and methods of use

A composition that provides sustained release of TIMP and comprises an injectable collagen, a polymer and at least one Tissue Inhibitor of Matrix Metalloprotease (TIMP). Also described is the use of the composition in the manufacture of a medicament for repair or augmentation of skin or tissue, treatment or prevention of urinary incontinence.

Drug delivery from rapid gelling polymer composition

Compositions are disclosed that afford drug delivery from two-part polymer compositions that rapidly form covalent linkages when mixed together. Such compositions are particularly well suited for use in a variety of tissue related applications when rapid adhesion to the tissue and gel formation is desired along with drug delivery. For example, the compositions are useful as tissue sealants, in promoting hemostasis, in effecting tissue adhesion, in providing tissue augmentation, and in the prevention of surgical adhesions.

Compositions comprising collagen and metalloprotease inhibitors

Compositions comprising collagen and at least one metalloprotease inhibitor, and methods of making and using same are provided.

Compositions and methods for coating medical implants

Perivascular wraps

The present invention provides compositions, devices, and methods for maintaining or improving the integrity of body passageways following surgery, such as at a graft site, or injury. Delivery devices including one or more therapeutic agents and a mesh are described. Representative examples of therapeutic agents include microtubule stabilizing agents, anti-angiogenic factors, inhibitors of smooth muscle cell growth or proliferation, non-steroidal anti-inflammaory drugs, and other factors useful preventing and/or reducing a proliferative biological response that may obstruct or hinder the optimal functioning of the passageway or cavity.

Compositions and methods for treating diverticular disease

Agents, compositions, and implants are provided herein for treating diverticular disease (e.g., diverticulosis and diverticulitis). In particular, fibrosis-inducing agents, hemostatic agents, and/or anti-infective agents, or compositions containing one or more of these agents are provided for use in methods for treating diverticular disease.

Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use

Kits comprising dry power compositions are provided that readily crosslink in situ to provide crosslinked biomaterials. The dry powder composition contains at least two biocompatible, non-immunogenic components having reactive groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. Exemplary uses for the crosslinked biomaterials include tissue augmentation, biologically active agent delivery, bioadhesion, and prevention of adhesions following surgery or injury.

Silk-containing stent graft

Silk-containing stent grafts are provided comprising an endoluminal stent and a graft, wherein the silk is induces the in vivo adhesion of the stent graft to vessel walls, or, otherwise induces or accelerates an in vivo fibrotic reaction causing said stent graft to adhere to vessel wall. Also provided are methods for making and using such stent grafts.

Sterile thiol-derivatized hyaluronic acid polymer compositions and uses thereof

The present application provides sterile hyaluronic polymer compositions than are useful, e.g., as medical devices, biomedical adhesives, and sealants. Generally, provided are sterile dry compositions comprising a soluble thiol-derivatized hyaluronic acid and one or more stabilizing excipients. Also provided are related kits and methods. The compositions described herein are particularly robust to sterilizing irradiation, and substantially maintain both their molecular weight and gelation parameters such as gelation time after sterilization, such that such sterile compositions are cabable of hydrogel formation.

Implantable sensors and implantable pumps and anti-scarring agents

Pumps and sensors for contact with tissue are used in combination with an anti-scarring agent (e.g., a cell cycle inhibitor) in order to inhibit scarring that may otherwise occur when the pumps and sensors are implanted within an animal.

Modified hyaluronic acid polymer compositions and related methods

The present application provides compositions comprising hyaluronic acid having low levels of functional group modification, mixtures formed by controlled reaction of such lightly modified hyaluronic acid with suitable difunctional or multi-functional crosslinkers, and hydrogel precursor compositions and the resulting hydrogels. The compositions are lightly cross-linked and possess low pro-inflammatory properties when injected in vivo, and can be used as, for example, medical devices, biomedical adhesives and sealants, and for localized delivery of bioactive agents, among other uses.

Perivascular wraps

The present invention provides compositions, devices, and methods for maintaining or improving the integrity of body passageways following surgery, such as at a graft site, or injury. Delivery devices including one or more therapeutic agents and a mesh are described. Representative examples of therapeutic agents include microtubule stabilizing agents, anti-angiogenic factors, inhibitors of smooth muscle cell growth or proliferation, non-steroidal anti-inflammaory drugs, and other factors useful preventing and/or reducing a proliferative biological response that may obstruct or hinder the optimal functioning of the passageway or cavity.

Compositions and methods for coating medical implants

Medical implants are provided which release an anthracycline, fluoropyrimidine, folic acid antagonist, podophylotoxin, camptothecin, hydroxyurea, and/or platinum complex, thereby inhibiting or reducing the incidence of infection associated with the implant.

Soft tissue implants and anti-scarring agents

Soft tissue implants (e.g., breast, pectoral, chin, facial, lip, and nasal implants) are used in combination with an anti-scarring agent in order to inhibit scarring that may otherwise occur when the implant is placed within an animal.

Implantable sensors and implantable pumps and anti-scarring agents

Pumps and sensors for contact with tissue are used in combination with an anti-scarring agent (e.g., a cell cycle inhibitor) in order to inhibit scarring that may otherwise occur when the pumps and sensors are implanted within an animal.

Sutures and anti-scarring agents

Sutures are used in combination with anti-scarring agents to inhibit fibrosis between the sutures and the host tissues into which the sutures are inserted. Compositions and methods are described for use in reducing excessive scarring, surgical adhesion, and other disorders.

Soft tissue implants and drug combination compositions, and use thereof

Soft tissue implants (e.g., breast, pectoral, chin, facial, lip, and nasal implants) are used in combination with an anti-scarring drug combination in order to inhibit scarring that may otherwise occur when the implant is placed within an animal.

Amino acids in micelle preparation

Formulations are formed of a diblock copolymer (X-Y) having a hydrophilic block X comprising residues of monomer x, and a hydrophobic block Y comprising residues of monomer y; an additive selected from an amino acid and an oligopeptide. Upon admixture with water, the formulations form drug delivery vehicles, preferably in micellar form. The inclusion of amino acid and/or oligopeptide provides for the formation of micelles at an enhanced rate, and/or provides the formation of micelles having an enhanced ability to incorporate drug(s), and/or provides the formation of micelles having advantageous physical characteristics.

Compositions and methods for coating medical implants

Medical implants are provided which release an anthracycline, fluoropyrimidine, folic acid antagonist, podophylotoxin, camptothecin, hydroxyurea, and/or platinum complex, thereby inhibiting or reducing the incidence of infection associated with the implant.

Silk-containing stent graft

Silk-containing stent grafts are provided comprising an endoluminal stent an d a graft, wherein the silk is induces the in vivo adhesion of the stent graft to vessel walls, or, otherwise induces or accelerates an in vivo fibrotic reaction causing said stent graft to adhere to vessel wall. Also provided ar e methods for making and using such stent grafts.

Drug delivery from rapid gelling polymer composition

Compositions are disclosed that afford drug delivery from two-part polymer compositions that rapidly form covalent linkages when mixed together. Such compositions are particularly well suited for use in a variety of tissue related applications when rapid adhesion to the tissue and gel formation is desired along with drug delivery. For example, the compositions are useful as tissue sealants, in promoting hemostasis, in effecting tissue adhesion, in providing tissue augmentation, and in prevention of surgical adhesions.

Functionalized and crosslinked polymers

Disclosed herein are compositions and methods of making and using such compositions. Polyhydric polymers may be converted to derivatives thereof by reaction with divinyl sulfone to provide vinyl sulfone substituted polymers, where the polymers may additionally be crosslinked, and the crosslinked and non-crosslinked derivatives may be used in biomedical and other applications.

Zusammensetzungen und verfahren zum beschichten von medizinischen implantaten

Soft tissue implants and drug combination compositions, and use thereof

Soft tissue implants (e.g., breast, pectoral, chin, facial, lip, and nasal implants) are used in combination with an anti-scarring drug combination in order to inhibit scarring that may otherwise occur when the implant is placed within an animal.

Multifunctional compounds for forming crosslinked biomaterials and methods of preparation and use

Multifunctional compounds are provided that readily crosslink in situ to provide crosslinked biomaterials. The multifunctional compounds contain a single component having at least three reactive functional groups thereon, with the functional groups selected so as to be non-reactive in an initial environment and inter-reactive in a modified environment. Reaction of a plurality of the multifunctional compounds results in a three-dimensional crosslinked matrix. In one embodiment, a first functional group is nucleophilic, a second functional group is electrophilic, and at least one additional functional group is nucleophilic or electrophilic. Methods for preparing and using the multifunctional compounds, and kits including the multifunctional compounds are also provided. Exemplary uses for the multifunctional compounds include tissue augmentation, biologically active agent delivery, bioadhesion, and prevention of adhesions following surgery or injury.

In-situ gel forming compositions

The present application provides rapid-gelling, sprayable hyaluronic-acid based compositions, kits, related methods, precursor formulations, and uses thereof.

Soft tissue implants, anti-scarring agents, and therapeutic compositions

Soft tissue implants (e.g., breast, pectoral, chin, facial, lip, and nasal implants) are used in combination with an anti-scarring agent in order to inhibit scarring that may otherwise occur when the implant is placed within an animal.

Rapid in-situ gel forming compositions prepared via reaction of vinyl sulfone derivatized hyaluronic acid with thiol derivatized polyethylene glycol at alkaline pH

The present application provides rapid-gelling, sprayable hyaluronic-acid based compositions, kits, related methods, precursor formulations, and uses thereof.

Modified hyaluronic acid polymer compositions and related methods

The present application provides compositions comprising hyaluronic acid having low levels of functional group modification, mixtures formed by controlled reaction of such lightly modified hyaluronic acid with suitable difunctional or multi-functional crosslinkers, and hydrogel precursor compositions and the resulting hydrogels. The compositions are lightly cross-linked and possess low pro-inflammatory properties when injected in vivo, and can be used as, for example, medical devices, biomedical adhesives and sealants, and for localized delivery of bioactive agents, among other uses.