US2003162841A1PendingUtilityA1

Biocompatible crosslinked polymers

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Assignee: INCEPTPriority: Dec 4, 1998Filed: Feb 25, 2003Published: Aug 28, 2003
Est. expiryDec 4, 2018(expired)· nominal 20-yr term from priority
Inventors:Chandrashekhar P. PathakAmarpreet S. SawhneyPeter Edelman
A61P 43/00A61P 41/00A61P 9/10A61P 35/00A61P 3/10A61P 29/00A61L 31/148A61K 9/0024A61P 19/02A61L 27/52A61L 27/58C08G 63/08A61L 31/06A61L 31/145A61K 47/46A61L 27/50A61K 47/34A61K 31/74C08G 63/912A61L 27/18
55
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Claims

Abstract

Biocompatible crosslinked-polymers, and methods for their preparation and use, are disclosed in which the biocompatible crosslinked polymers are formed from water soluble precursors having electrophilic and nucleophilic groups capable of reacting and crosslinking in situ. Methods for making the resulting biocompatible crosslinked polymers biodegradable or not are provided, as are methods for controlling the rate of degradation. The crosslinking reactions may be carried out in situ on organs or tissues or outside the body. Applications for such biocompatible crosslinked polymers and their precursors include controlled delivery of drugs, prevention of post-operative adhesions, coating of medical devices such as vascular grafts, wound dressings and surgical sealants.

Claims

exact text as granted — not AI-modified
1 . A biocompatible material comprising: 
 a covalently crosslinked hydrogel formed by the reaction of at least one crosslinkable polymer with at least one synthetic crosslinker to form the hydrogel, wherein the hydrogel comprises at least one reinforcing component, and wherein before reaction at least one of the crosslinker or crosslinkable polymer has at least three reactive moieties per molecule and at least one biodegradable region.    
     
     
         2 . The biocompatible material of  claim 1  wherein the reinforcement component enhances flexibility of the hydrogel.  
     
     
         3 . The biocompatible material of  claim 1  wherein the reinforcing component is selected from the group consisting of flexible fibers, rigid fibers, fiber mesh, fiber cloth and combinations thereof.  
     
     
         4 . The biocompatible material of  claim 1  wherein the reinforcing component is selected from the group consisting of oxidized cellulose and poly(hydroxy acid).  
     
     
         5 . The biocompatible material of  claim 4  wherein the poly(hydroxy acid) comprises polylactic acid.  
     
     
         6 . The biocompatible material of  claim 1  wherein the crosslinker, the crosslinkable polymer, or both comprise a core unit, an extension at each end of the core unit and an end cap on the extension that comprises a reactive moiety.  
     
     
         7 . The biocompatible material of  claim 6  wherein the core unit comprises a water soluable polymeric region.  
     
     
         8 . The biocompatible material of  claim 6  wherein the core unit is biodegradable.  
     
     
         9 . The biocompatible material of  claim 6  wherein the core unit is not biodegradable.  
     
     
         10 . The biocompatible material of  claim 6  wherein the core unit comprises a polymeric region selected from the group consisting of polyalkylene oxide, polyethylene oxide-co-polypropylene oxide-co-polyethylene oxide block or random copolymers, polyvinyl alcohol, poly(vinyl pyrrolidinone), poly(amino acids), polyethyloxzoline and dextran.  
     
     
         11 . The biocompatible material of  claim 6  wherein the extension is a biodegradable extension.  
     
     
         12 . The biocompatible material of  claim 11  wherein the biodegradable extension is selected from the group consisting of polymers of glycolide, dl-lactide, 1-lactide, caprolactone, dioxanone, trimethylene carbonate, and copolymers thereof.  
     
     
         13 . The biocompatible material of  claim 11  wherein the biodegradable extension comprises enzymatically hydrolizable extension components.  
     
     
         14 . The biocompatible material of  claim 11  wherein the biodegradable extension comprises regions selected from the group consisting of poly(hydroxy acid)s, poly(orthocarbonate)s, poly(anhydride)s, poly(lactone)s, poly(aminoacid)s, poly(carbonate)s, and poly(phosphonate)s.  
     
     
         15 . The biocompatible material of  claim 6  wherein the reactive moiety is selected from the functional groups consisting of carbonyldiimidazole, sulfonyl chloride, aryl halides, sulfosuccinimidyl esters, N-hydroxysuccinimidyl ester, succinimidly ester, epoxide, aldehyde, maleimides, and imidoesters.  
     
     
         16 . The biocompatible material of  claim 6  wherein the reactive moiety comprises a primary amine.  
     
     
         17 . The biocompatible material of  claim 6  wherein the reactive moiety comprises a thiol.  
     
     
         18 . A system for applying a biomaterial, the system comprising: 
 a crosslinkable polymer;    a crosslinker reactable with the crosslinkable polymer to form a crosslinked hydrogel;    a reinforcing component; and    an applicator, wherein the applicator can deliver the crosslinker, crosslinkable polymer and reinforcing component to a surgical site in situ, and wherein before reaction at least one of the crosslinker or crosslinkable polymer has at least three reactive moieties per molecule and at least one biodegradable region.    
     
     
         19 . The system of  claim 18  further comprising instructions for applying the hydrogel.  
     
     
         20 . The system of  claim 18  wherein the applicator comprises a double barrel syringe.  
     
     
         21 . The system of  claim 18  wherein the reinforcing component is selected from the group consisting of flexible fibers, rigid fibers, fiber mesh, fiber cloth and combinations thereof.  
     
     
         22 . The system of  claim 18  wherein the reinforcing component is selected from the group consisting of oxidized cellulose and poly(hydroxy acid).  
     
     
         23 . The system of  claim 22  wherein the poly(hydroxy acid) comprises polylactic acid.  
     
     
         24 . The system of  claim 18  wherein the crosslinker, crosslinkable polymer, or both comprise a core unit, an extension at each end of the core unit and an end cap on the extension that comprises a reactive moiety.  
     
     
         25 . The system of  claim 24  wherein the core unit comprises a water soluble polymeric region.  
     
     
         26 . The system of  claim 24  wherein the core unit is biodegradable.  
     
     
         27 . The system of  claim 24  wherein the core unit is not biodegradable.  
     
     
         28 . The system of  claim 24  wherein the core unit comprises a polymeric region selected from the group consisting of polyalkylene oxide, polyethylene oxide-co-polypropylene oxide-co-polyethylene oxide block or random copolymers, polyvinyl alcohol, poly(vinyl pyrrolidinone), poly(amino acids), polyethyloxzoline and dextran.  
     
     
         29 . The system of  claim 24  wherein the extension is a biodegradable extension.  
     
     
         30 . The system of  claim 29  wherein the biodegradable extension is selected from the group consisting of polymers of glycolide, dl-lactide, 1-lactide, caprolactone, dioxanone, trimethylene carbonate, and copolymers thereof.  
     
     
         31 . The system of  claim 29  wherein the biodegradable extension comprises enzymatically hydrolizable extension components.  
     
     
         32 . The system of  claim 29  wherein the biodegradable extension comprise regions selected from the group consisting of poly(hydroxy acid)s, poly(orthocarbonate)s, poly(anhydride)s, poly(lactone)s, poly(aminoacid)s, poly(carbonate)s, and poly(phosphonate)s.  
     
     
         33 . The system of  claim 24  wherein the reactive moiety is selected from the functional groups consisting of carbonyldiimidazole, sulfonyl chloride, aryl halides, sulfosuccinimidyl esters, N-hydroxysuccinimidyl ester, succinimidly ester, epoxide, aldehyde, maleimides, and imidoesters.  
     
     
         34 . The system of  claim 24  wherein the reactive moiety comprises a primary amine.  
     
     
         35 . The system of  claim 24  wherein the reactive moiety comprises a thiol.  
     
     
         36 . A biocompatible material comprising: 
 a covalently crosslinked hydrogel formed by the reaction of at least one crosslinkable polymer with at least one synthetic crosslinker to form the hydrogel, wherein the hydrogel comprises means for reinforcing the hydrogel, and wherein before reaction at least one of the synthetic crosslinker or crosslinkable polymer has at least three reactive moieties per molecule and at least one biodegradable region.

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