Imageable polymers

Abstract

This invention relates to imageable polymers, particularly those comprising poly vinylalcohol and to methods for making them as well as to embolic microspheres comprising the polymers. The microspheres are imageable during embolization procedures and can be loaded with drugs or other therapeutic agents to provide an imageable drug delivery system.

1 - 37 . (canceled) 
     
     
         38 . A hydrogel comprising a cross-linked polymer network comprising a polymer having 1,2-diol or 1,3-diol groups and a radiopaque species covalently bound to the polymer through a cyclic acetal group, the radiopaque species comprising one or more covalently bound radiopaque halogens. 
     
     
         39 . A hydrogel according to  claim 38  wherein the radiopaque species comprises an iodinated aromatic group. 
     
     
         40 . A hydrogel according to  claim 38  wherein the radiopaque species comprises a brominated aromatic group. 
     
     
         41 . A hydrogel according to  claim 38  wherein the hydrogel comprises polyvinyl alcohol (PVA) in which the PVA comprises pendent groups formed from the acetalisation of PVA with N-acryloyl-aminoacetaldehyde dimethylacetal and which is cross-linked with 2-acrylamido-2-methylpropanesulfonic acid (PVA-AMPS). 
     
     
         42 . A hydrogel according to  claim 38  wherein the one or more covalently bound radiopaque halogens comprise bromine. 
     
     
         43 . A hydrogel according to  claim 38  wherein the one or more covalently bound radiopaque halogens comprise iodine. 
     
     
         44 . A hydrogel according to  claim 43  wherein the radiopaque species comprises an iodinated phenyl group. 
     
     
         45 . A hydrogel according to  claim 43  wherein the hydrogel comprises greater than 10% iodine by dry weight. 
     
     
         46 . A hydrogel according to  claim 38  wherein the hydrogel is in the form of microparticles or microspheres. 
     
     
         47 . A hydrogel according to  claim 46  wherein the hydrogel is in the form of microspheres with a mean diameter size range of from 10 to 2000 μm. 
     
     
         48 . A hydrogel according to  claim 38  in the form of microspheres or microparticles having a mean radiopacity of 500HU or greater. 
     
     
         49 . A hydrogel according to  claim 38  wherein the hydrogel has a net charge at physiological pH. 
     
     
         50 . A hydrogel according to  claim 38  comprising a structure of the general formula I or II 
       
         
           
           
               
               
           
         
         wherein X is a group substituted by one or more halogens and preferably one or more iodine moieties and J is a group of the formula —CH 2 — or is a bond. 
       
     
     
         51 . A hydrogel according to  claim 50  wherein X is a group of the formula 
       
         
           
           
               
               
           
         
         wherein Z is a linking group, or is absent, such that the phenyl group is bonded to the cyclic acetal; 
         if Z is present, then Z is C 1-6  alkylene, C 1-6  alkoxylene or C 1-6  alkoxyalkylene; 
         Hal is 1, 2, 3 or 4 covalently attached radiopaque halogens. 
       
     
     
         52 . A composition comprising a hydrogel according to  claim 38  and a therapeutic agent wherein the therapeutic agent is absorbed into the hydrogel matrix. 
     
     
         53 . A composition according to  claim 52  wherein the therapeutic agent is electrostatically held in the hydrogel and elutes from the hydrogel in electrolytic media. 
     
     
         54 . A method of treatment in which a hydrogel according to  claim 38  is administered into a blood vessel of a patient to embolize said blood vessel. 
     
     
         55 . A method according to  claim 54  in which the blood vessel is associated with solid tumor. 
     
     
         56 . A method according to  claim 55  in which the tumor is hepatocellular carcinoma. 
     
     
         57 . A hydrogel according to  claim 38  for use in embolization of a blood vessel.