Methods and polymer compositions for treating retinal detachment and other ocular disorders

Abstract

The invention provides methods and polymer compositions for treating retinal detachment and other ocular disorders, where the methods employ polymer compositions that can form a hydrogel in the eye of a subject. The hydrogel is formed by reaction of (i) a nucleo-functional polymer that is a biocompatible polymer containing a plurality of thio-functional groups —R1—SH wherein R1 is an ester-containing linker, such as a thiolated poly(vinyl alcohol) polymer and (ii) an electro-functional polymer that is a biocompatible polymer containing at least one thiol-reactive group, such as a poly(ethylene glycol) polymer containing alpha-beta unsaturated ester groups.

What is claimed is: 
     
         1 - 80 . (canceled) 
     
     
         81 . An injectable, ocular formulation for forming a hydrogel in the eye of a subject, the formulation comprising:
 a. a nucleo-functional polymer that is a biocompatible polymer containing a plurality of thio-functional groups —R 1 —SH wherein R 1  is an ester-containing linker;   b. an electro-functional polymer that is a biocompatible polymer containing at least one thiol-reactive group;   c. a liquid pharmaceutically acceptable carrier for administration to the eye of a subject.   
     
     
         82 . The formulation of  claim 81 , wherein the nucleo-functional polymer is a biocompatible polymer selected from a polyalkylene and polyheteroalkylene polymer each being substituted by (i) a plurality of thio-functional groups —R 1 —SH, and optionally (ii) one or more hydroxyl, alkyl ester, hydroxyalkyl ester, or amide groups. 
     
     
         83 . The formulation of  claim 81 , wherein the nucleo-functional polymer is a biocompatible polyalkylene polymer substituted by (i) a plurality of thio-functional groups —R 1 —SH and (ii) a plurality of groups selected from the group consisting of hydroxyl, alkyl ester, hydroxyalkyl ester, and amide. 
     
     
         84 . The formulation of  claim 81 , wherein the nucleo-functional polymer is a biocompatible polymer selected from poly(vinyl alcohol), poly(vinyl alcohol methacrylate), polyacrylamide, or poly(2-hydroxyethyl methacrylate), each being substituted by a plurality of thio-functional groups —R 1 —SH. 
     
     
         85 . The formulation of  claim 81 , wherein the nucleo-functional polymer is a biocompatible poly(vinyl alcohol) polymer substituted by a plurality of thio-functional groups —R 1 —SH. 
     
     
         86 . The formulation of  claim 81 , wherein the nucleo-functional polymer is a biocompatible, partially hydrolyzed poly(vinyl alcohol) polymer substituted by a plurality of thio-functional groups —R 1 —SH. 
     
     
         87 . The formulation of  claim 81 , wherein the nucleo-functional polymer is a biocompatible, partially hydrolyzed poly(vinyl alcohol) polymer substituted by a plurality of thio-functional groups —R 1 —SH, wherein the degree of hydrolysis of the partially hydrolyzed poly(vinyl alcohol) polymer is at least 95%. 
     
     
         88 . The formulation of  claim 81 , wherein the thio-functional group —R 1 —SH is —OC(O)—(C 1 -C 6  alkylene)-SH. 
     
     
         89 . The formulation of  claim 81 , wherein the thio-functional group —R 1 —SH is —OC(O)—(CH 2 CH 2 )—SH 
     
     
         90 . The formulation of  claim 81 , wherein the nucleo-functional polymer is a biocompatible poly(vinyl alcohol) polymer comprising: 
       
         
           
           
               
               
           
         
       
       wherein a is an integer from 1-10 and b is an integer from 1-10. 
     
     
         91 . The formulation of  claim 81 , wherein the nucleo-functional polymer is a biocompatible poly(vinyl alcohol) polymer comprising: 
       
         
           
           
               
               
           
         
       
       wherein a is an integer from 1-10, b is an integer from 1-10, and c is an integer from about 20 to about 500. 
     
     
         92 . The formulation of  claim 81 , wherein the nucleo-functional polymer has a weight-average molecular weight in the range of from about 500 g/mol to about 1,000,000 g/mol. 
     
     
         93 . The formulation of  claim 81 , wherein the nucleo-functional polymer has a weight-average molecular weight in the range of from about 2,000 g/mol to about 500,000 g/mol. 
     
     
         94 . The formulation of  claim 81 , wherein the nucleo-functional polymer has a weight-average molecular weight in the range of from about 4,000 g/mol to about 30,000 g/mol. 
     
     
         95 . The formulation of  claim 81 , wherein the nucleo-functional polymer has a weight-average molecular weight in the range of from about 26,000 g/mol to about 32,000 g/mol. 
     
     
         96 . The formulation of  claim 81 , wherein the nucleo-functional polymer has a weight-average molecular weight of about 30,000 g/mol. 
     
     
         97 . The formulation of  claim 81 , wherein the nucleo-functional polymer has a weight-average molecular weight in the range of from about 45,000 g/mol to about 55,000 g/mol. 
     
     
         98 . The formulation of  claim 81 , wherein the nucleo-functional polymer has a weight-average molecular weight of about 50,000 g/mol. 
     
     
         99 . The formulation of  claim 81 , wherein the electro-functional polymer is a biocompatible polymer selected from a polyalkylene and polyheteroalkylene polymer each being substituted by at least one thiol-reactive group. 
     
     
         100 . The formulation of  claim 81 , wherein the electro-functional polymer is a biocompatible polyheteroalkylene polymer substituted by at least one thiol-reactive group. 
     
     
         101 - 127 . (canceled)