Polyanhydride linkers for production of drug polymers and drug polymer compositions produced thereby

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.

What is claimed is:  
     
         1 . A composition comprising Formula (I):  
       
         
           
           
               
               
           
         
       
       wherein R 1  is selected from the group consisting of alkyls, cycloalkyls, substituted alkyls, aromatics, substituted aromatics, lactams, and lactones; 
 X is selected from the group consisting of amides, thioamides, esters and thioesters; and  
 R 2  is an alkyl represented by —(CH 2 ) n , wherein n is from 1 to 20.  
 
     
     
         2 . The composition of  claim 1  further comprising low molecular weight drug molecules linked via Formula I, wherein each low molecular drug molecule comprises within its structure one carboxylic acid group and at least one amine, thiol, alcohol or phenol group.  
     
     
         3 . A method of delivering a low molecular weight drug to a patient comprising administering to the patient a composition of  claim 2 .  
     
     
         4 . A polymeric drug delivery system comprising low molecular weight drug molecules linked via a polyanhydride wherein each low molecular weight drug molecule comprises within its structure one carboxylic acid group and at least one amine, thiol, alcohol or phenol group and wherein the polyanhydride comprises Formula (I)  
       
         
           
           
               
               
           
         
       
       wherein R 1  is selected from the group consisting of alkyls, cycloalkyls, substituted alkyls, aromatics, substituted aromatics, lactams, and lactones; 
 X is selected from the group consisting of amides, thioamides, esters and thioesters; and  
 R 2  is an alkyl represented by —(CH 2 )  n , wherein n is from 1 to 20.  
 
     
     
         5 . A method of linking low molecular weight drug molecules containing within their structure one carboxylic acid group and at least one amine, thiol, alcohol or phenol group into polymeric drug delivery systems comprising: 
 (a) protecting the carboxylic acid group of the low molecular weight drug molecules;    (b) adding to the low molecular weight drug molecules a chlorinated polyanhydride linker of Formula II                          wherein n is from 1 to 20,    so that drug molecules displace the chlorine groups of the polyanhydride linker of Formula (II) and bind to the linker via their amine, thiol, alcohol-or phenol group; and    (c) exposing the linked drug molecules to heat or vacuum so that the protecting groups are removed.