Polymers and methods thereof for wound healing

Abstract

Certain embodiments of the invention provide a copolymer having a backbone, wherein the backbone comprises a) one or more units that comprise a group that will yield a biologically active agent upon hydrolysis of the backbone; and b) one or more units of formula (II): wherein y is 1 or more. Other embodiments of the invention provide a therapeutic method for treating a wound in an animal comprising administering to an animal in need of such therapy, an effective amount of a copolymer as described herein.

What is claimed is: 
     
         1 . A copolymer having a backbone, wherein the backbone comprises a) one or more units that comprise a group that will yield a biologically active agent upon hydrolysis of the backbone; and b) one or more units of formula (II): 
       
         
           
           
               
               
           
         
         wherein y is 1 or more. 
       
     
     
         2 . The copolymer of  claim 1 , wherein the one or more units that comprise a group that will yield a biologically active agent upon hydrolysis of the backbone is a polyanhydride. 
     
     
         3 . The copolymer of  claim 2 , wherein the polyanhydride comprises one or more units of formula (I) in the backbone:
   —C(═O)R 1 -A-L-A-R 1 C(═O)—O  (I)
   wherein
 each R 1  is a group that will provide a biologically active agent upon hydrolysis of the polymer; 
 each A is independently an ester or an amide linkage; and 
 each L is independently a linker molecule. 
   
     
     
         4 . The copolymer of  claim 3 , wherein A is independently an ester linkage. 
     
     
         5 . The copolymer of  claim 3 , wherein L is a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain, having from 1 to 25 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (—O—), (—NR—) or phenylene, and wherein the chain is optionally substituted on carbon with one or more substituents selected from the group consisting of (C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkylthio, azido, cyano, nitro, halo, hydroxy, oxo, carboxy, aryl, aryloxy, heteroaryl, and heteroaryloxy wherein each R is independently selected from H or (C 1 -C 6 )alkyl. 
     
     
         6 . The copolymer of  claim 3 , wherein L is —CH 2 CH 2 CH 2 CH 2 — or —CH 2 C(Et) 2 CH 2 —. 
     
     
         7 . The copolymer of  claim 1 , wherein the biologically active agent is an antimicrobial, anti-inflammatory, antioxidant, analgesic, anticoagulant or fibrinolytic. 
     
     
         8 . The copolymer of  claim 7 , wherein the biologically active agent is an anti-inflammatory agent. 
     
     
         9 . The copolymer of  claim 8 , wherein the anti-inflammatory agent is salicylic acid. 
     
     
         10 . The copolymer of  claim 1 , wherein the ratio of the a) one or more units that comprise a group that will yield a biologically active agent upon hydrolysis of the backbone to the b) one or more units of formula (II), ranges from between about 5:1 to about 1:5. 
     
     
         11 . The copolymer of  claim 10 , wherein the ratio ranges from 2:1 to 1:2. 
     
     
         12 . The copolymer of  claim 11 , wherein the ratio is 1:1 or 2:1. 
     
     
         13 . The copolymer of  claim 1  comprising one or more units of formula (III): 
       
         
           
           
               
               
           
         
         wherein each L is independently a linker molecule;
 x is 5 or more; 
 y is 1 or more; and 
 z is 5 or more. 
 
       
     
     
         14 . The copolymer of  claim 1  which has an average molecular weight of about 10,000 daltons to about 30,000 daltons. 
     
     
         15 . The copolymer of  claim 1 , further comprising a second biologically active agent dispersed in the matrix of the copolymer. 
     
     
         16 . A pharmaceutical composition comprising a copolymer of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         17 . A method of making a copolymer as described in  claim 1  comprising co-polymerizing (a) one or more monomer(s) that comprises one or more units that comprise a group that will yield a biologically active agent upon hydrolysis of the backbone; and (b) one or more monomer(s) that comprises one or more units of formula (II); under conditions to provide the polymer. 
     
     
         18 . A therapeutic method for treating a wound in an animal comprising administering to an animal in need of such therapy an effective amount of a copolymer as described in  claim 1 . 
     
     
         19 . A therapeutic method for the prevention of fibrous adhesions at a wound site in an animal comprising administering to an animal in need of such therapy an effective amount of a copolymer as described in  claim 1 . 
     
     
         20 . A therapeutic method for providing localized analgesia at a wound site in an animal comprising administering to an animal in need of such therapy an effective amount of a copolymer as described in  claim 1 .