Linear cyclodextrin copolymers

Abstract

Linear cyclodextrin copolymers and linear oxidized cyclodextrin copolymers containing an unoxidized and/or an oxidized cyclodextrin moiety integrated into the polymer backbone are described. Methods of preparing such copolymers are also described. The linear cyclodextrin copolymer and linear oxidized cyclodextrin copolymer of the invention may be used as a delivery vehicle of various therapeutic agents.

1 - 70 . (canceled) 
     
     
         71 . A method of preparing a β-cyclodextrin-dimethylsuberimidate (DMS) copolymer, comprising:
 (a) reacting a β-cyclodextrin with biphenyl-4,4′-disulfonyl chloride to generate a biphenyl-4,4′-disulfonyl-A,D-capped β-cyclodextrin; 
 (b) reacting said biphenyl-4,4′-disulfonyl-A,D-capped β-cyclodextrin with potassium iodide to generate a 6 A ,6 D -diiodo-6 A ,6 D -deoxy-β-cyclodextrin; 
 (c) reacting said 6 A ,6 D -diiodo-6 A ,6 D -deoxy-β-cyclodextrin with 2-aminoethanethiol to generate a 6 A ,6 D -bis-(2-aminoethylthio)-6 A ,6 D -deoxy-β-cyclodextrin; and 
 (d) reacting said 6 A ,6 D -bis-(2-aminoethylthio)-6 A ,6 D -deoxy-β-cyclodextrin with DMS to generate said β-cyclodextrin-dimethylsuberimidate (DMS) copolymer. 
 
     
     
         72 . The method of  claim 71 , wherein said β-cyclodextrin is charged with anhydrous pyridine prior to reaction with biphenyl-4,4′-disulfonyl chloride in (a). 
     
     
         73 . The method of  claim 71 , further comprising acidifying said 6 A ,6 D -diiodo-6 A ,6 D -deoxy-β-cyclodextrin and 2-aminoethanethiol in (c). 
     
     
         74 . The method of  claim 71 , further comprising acidifying said 6 A ,6 D -bis-(2-aminoethylthio)-6 A ,6 D -deoxy-β-cyclodextrin and DMS in (d) to pH 4. 
     
     
         75 . The method of  claim 71 , further comprising reacting said β-cyclodextrin-dimethylsuberimidate (DMS) copolymer with an imidazole. 
     
     
         76 . A method of preparing a β-cyclodextrin-dimethylsuberimidate (DMS) copolymer having the following structure: 
       
         
           
           
               
               
           
         
         said method comprising: 
         (a) charging dry β-cyclodextrin with anhydrous pyridine, followed by reacting with biphenyl-4,4′-disulfonyl chloride to generate a biphenyl-4,4′-disulfonyl-A,D-capped β-cyclodextrin; 
         (b) reacting said biphenyl-4,4′-disulfonyl-A,D-capped β-cyclodextrin with potassium iodide at 80° C. to generate a 6 A ,6 D -diiodo-6 A ,6 D -deoxy-β-cyclodextrin; 
         (c) reacting said 6 A ,6 D -diiodo-6 A ,6 D -deoxy-β-cyclodextrin with 2-aminoethanethiol, followed by cooling to room temperature and acidifying, to generate a 6 A ,6 D -Bis-(2-aminoethylthio)-6 A ,6 D -deoxy-β-cyclodextrin; and 
         (d) reacting said 6 A ,6 D -bis-(2-aminoethylthio)-6 A ,6 D -deoxy-β-cyclodextrin with DMS, followed by redissolving in water and acidifying to pH 4, to generate said β-cyclodextrin-dimethylsuberimidate (DMS) copolymer. 
       
     
     
         77 . The method of  claim 76 , further comprising reacting said β-cyclodextrin-dimethylsuberimidate (DMS) copolymer with an imidazole. 
     
     
         78 . A β-cyclodextrin-dimethylsuberimidate (DMS) copolymer prepared by the method of  claim 76 . 
     
     
         79 . A β-cyclodextrin-dimethylsuberimidate (DMS) copolymer prepared by the method of  claim 77 . 
     
     
         80 . A therapeutic composition comprising the β-cyclodextrin-dimethylsuberimidate (DMS) copolymer of  claim 78  and a therapeutic agent selected from antibiotics, steroids, polynucleotides, plasmids, peptides, peptide fragments, small molecules, proteins, and enzymes. 
     
     
         81 . A method of delivering a therapeutic agent comprising administering a therapeutically effective amount of the therapeutic composition of  claim 80  to a subject in need of said therapeutic agent. 
     
     
         82 . A method of delivering a therapeutic agent comprising:
 combining the β-cyclodextrin-dimethylsuberimidate (DMS) copolymer of  claim 78  with a therapeutic agent to form a mixture;   allowing said mixture to self-assemble to form an associated composition; and   administering a therapeutically effective amount of said associated composition to a subject in need of said therapeutic agent,   wherein said therapeutic agent is selected from antibiotics, steroids, polynucleotides, plasmids, peptides, peptide fragments, small molecules, proteins, and enzymes.