Therapeutic polyanhydride compounds for drug delivery

Abstract

Polyanhydrides which link low molecular weight drugs containing a carboxylic acid group and an amine, thiol, alcohol or phenol group within their structure into polymeric drug delivery systems are provided. Also provided are methods of producing polymeric drug delivery systems via these polyanhydride linkers as well as methods of administering low molecular weight drugs to a host via the polymeric drug delivery systems.

1 . A medical device comprising a polymer that comprises a backbone, wherein the backbone comprises an anhydride linkage, wherein the backbone comprises one or more groups that will yield a biologically active compound upon hydrolysis of the polymer, provided that the biologically active compound is not an ortho-hydroxy aryl carboxylic acid or an alpha-hydroxy carboxylic acid.  
     
     
         2 . The medical device of  claim 1 , wherein the medical device is a stent, a vascular graft, a bone plate, a suture, an implantable sensor, or an implantable drug delivery device.  
     
     
         3 . The medical device of  claim 2 , wherein the medical device is a stent.  
     
     
         4 . The medical device of  claim 1 , wherein the biologically active compound is an anti-inflammatory compound.  
     
     
         5 . The medical device of  claim 1 , wherein the biologically active compound is an antibiotic compound.  
     
     
         6 . The medical device of  claim 1 , wherein the biologically active compound is an antineoplastic compound.  
     
     
         7 . The medical device of  claim 1 , wherein the polymer is comprised in a coating.  
     
     
         8 . The medical device of  claim 1 , wherein the polymer comprises one or more units of formula (I) in the backbone:  
         —C(═O)R 1 —X—R 2 —X—R 1 —C(═O)—O—  (I)  
       wherein 
 each R 1  is a group that will provide a biologically active compound upon hydrolysis of the polymer;  
 each X is independently an amide linkage, a thioester linkage, or an ester linkage; and  
 R 2  is a linking group.  
 
     
     
         9 . The medical device of  claim 8 , wherein R 2  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—) or (—NR—), and wherein the chain is optionally substituted on at least one carbon atom with one or more substituents (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, or heteroaryloxy.  
     
     
         10 . The medical device of  claim 8 , wherein R 2  is a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain, having from 1 to 25 carbon atoms, wherein the chain is optionally substituted on at least one carbon atom with one or more substituents (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.  
     
     
         11 . The medical device of  claim 8 , wherein R 2  is an amino acid.  
     
     
         12 . The medical device of  claim 8 , wherein R 2  is a peptide.  
     
     
         13 . The medical device of  claim 8 , wherein R 2  is a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 3 to 15 carbon atoms.  
     
     
         14 . The medical device of  claim 8 , wherein R 2  is a divalent, branched or unbranched, hydrocarbon chain, having from 3 to 15 carbon atoms.  
     
     
         15 . The medical device of  claim 14 , wherein R 2  is a divalent, branched or unbranched, hydrocarbon chain, having from 6 to 10 carbon atoms.  
     
     
         16 . The medical device of  claim 15 , wherein R 2  is a divalent hydrocarbon chain having 7, 8, or 9 carbon atoms.  
     
     
         17 . The medical device of  claim 16 , wherein R 2  is a divalent hydrocarbon chain having 8 carbon atoms.  
     
     
         18 . The medical device of  claim 8 , wherein the one or more units of formula (I) are one or more units of formula (II) or (III):  
         —C(O)R 1 —OC(O)—R 2 —(O)CO—R 1 —C(O)—O—  (II)  —C(O)R 1 —C(O)O—R 2 —(O)OC—R 1 —C(O)—O—  (III).  
     
     
         19 . The medical device of  claim 19 , wherein the one or more units of formula (I) are one or more units of formula (II).  
     
     
         20 . The medical device of  claim 19 , wherein the one or more units of formula (I) are one or more units of formula (III).