PEG-Poly(Ortho Ester) Graft Copolymers and Pharmaceutical Compositions

Abstract

This invention relates to graft copolymer delivery vehicles comprising a polyethyleneglycol-poly(ortho ester), and to controlled release pharmaceutical compositions comprising the delivery vehicle and an active agent. The graft copolymer delivery vehicles may be thermogels graft copolymers. The pharmaceutical compositions may be in the form of a topical, syringable, or injectable formulation for local controlled delivery of the active agent.

1 - 91 . (canceled) 
   
   
       92 . A graft copolymer of Formula I: 
     
       
         
         
             
             
         
       
     
     wherein:
 n is an integer from 2 to 500; 
 p and q are independently integers from 5 to 100; 
 R 1  is —C 1 -C 4  alkyl; 
 R, R 2  and R 3  are each independently H or C 1 -C 4  alkyl; and 
 each A is R 5  where R 5  is: 
 
     
       
         
         
             
             
         
       
       
         where m′ is an integer from 1 to 6. 
       
     
   
   
       93 . The copolymer of  claim 92 , wherein R 2  is H 
   
   
       94 . The copolymer of  claim 92 , wherein R is H. 
   
   
       95 . The copolymer of  claim 94 , wherein R 1  is ethyl and R 2  is H. 
   
   
       96 . The copolymer of  claim 93  where A is R 5  and R 5  is 1,4-cyclohexanedimethylene. 
   
   
       97 . The copolymer of  claim 93 , wherein R 3  is methyl. 
   
   
       98 . The copolymer of  claim 97 , where A is R 5  and R 5  is 1,4-cyclohexanedimethylene. 
   
   
       99 . The copolymer of  claim 97 , wherein A is R 5  and R 5  is 1,4-cyclohexanedimethylene, and n is an integer from 50 to 250, and p is an integer from 10 to 50. 
   
   
       100 . A pharmaceutical composition comprising:
 (a) an active agent; and   (b) as a vehicle, the copolymer of graft copolymer of Formula I:   
     
       
         
         
             
             
         
       
     
     wherein:
 n is an integer from 2 to 500; 
 p and q are independently integers from 5 to 100; 
 R 1  is —C 1 -C 4  alkyl; 
 R, R 2  and R 3  are each independently H or C 1 -C 4  alkyl; and 
 each A is R 5  where R 5  is: 
 
     
       
         
         
             
             
         
       
       where m′ is an integer from 1 to 6. 
     
   
   
       101 . The pharmaceutical composition of  claim 100 , where the fraction of the active agent is from 1% to 60% by weight of the composition. 
   
   
       102 . The pharmaceutical composition of  claim 101 , where the fraction of the active agent is from 5% to 30% by weight of the composition. 
   
   
       103 . The pharmaceutical composition of  claim 100 , where the active agent is selected from anti-infectives, antiseptics, steroids, therapeutic polypeptides, proteins, anti-inflammatory agents, cancer chemotherapeutic agents, narcotics, antiemetics, local anesthetics, antiangiogenic agents, vaccines, antigens, oligonucleotides, RNA, DNA and antisense oligonucleotides. 
   
   
       104 . The pharmaceutical composition of  claim 103 , where the active agent is a local anesthetic. 
   
   
       105 . The pharmaceutical composition of  claim 103 , where the active agent is a cancer chemotherapeutic agent.