Non-degradable, low swelling, water soluble radiopaque hydrogel polymer

Abstract

Hydrogel compositions prepared from amine components and glycidyl ether components are provided which are biocompatible and suitable for use in vivo due, in part, to their excellent stability.

1 . An in situ formed hydrogel polymer, comprising: 
 (a) a first amount of a diamine; and    (b) a second amount of a polyglycidyl ether;    wherein each of (a) and (b) are present in a mammal or in a medical device located in a mammal in an amount to produce an in situ formed hydrogel polymer that is biocompatible; and has a cure time after mixing of from about 10 seconds to about 30 minutes; and    wherein the volume of said hydrogel polymer swells less than 30 percent after curing and hydration.    
     
     
         2 . The composition of  claim 1 , further comprising a radiopaque material.  
     
     
         3 . The composition of  claim 1 , wherein said radiopaque material is selected from the group consisting of sodium iodide, potassium iodide, barium sulfate, Visipaque 320, Hypaque, Omnipaque 350 and Hexabrix.  
     
     
         4 . The composition of  claim 1 , wherein said polyglycidyl ether is selected from the group consisting of trimethylolpropane triglycidyl ether, sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether, pentaerythritol polyglycidyl ether, diglycerol polyglycidyl ether, glycerol polyglycidyl ether, trimethylolpropane polyglycidyl ether, polyethylene glycol diglycidyl ether, resorcinol diglycidyl ether, glycidyl ester ether of p-hydroxy benzoic acid, neopentyl glycol diglycidyl ether, 1,6-hexanediol diglycidyl ether, bisphenol A (PO) 2  diglycidyl ether, hydroquinone diglycidyl ether, bisphenol S diglycidyl ether, terephthalic acid diglycidyl ester, and a mixture thereof.  
     
     
         5 . The composition of  claim 1 , wherein said diamine is selected from the group consisting of (poly)alkylene glycol having amino or alkylamino termini selected from the group consisting of polyethylene glycol (400) diamine, di-(3-aminopropyl) diethylene glycol r, polyoxypropylenediamine, polyetherdiamine, polyoxyethylenediamine, triethyleneglycol diamine, and a mixture thereof.  
     
     
         6 . The composition of  claim 1 , wherein said diamine is hydrophilic and said polyglycidyl ether is hydrophilic prior to curing.  
     
     
         7 . The composition of  claim 1 , wherein said diamine is hydrophilic and said polyglycidyl ether is hydrophobic prior to curing.  
     
     
         8 . The composition of  claim 1 , wherein said diamine is hydrophobic and said polyglycidyl ether is hydrophilic prior to curing.  
     
     
         9 . The composition of  claim 1 , wherein said in situ formed polymer is present in a mammal or in a medical device located in the mammal in an intraluminal graft, as an embolization device, in an inflatable occlusion member, as a tissue bulking device.  
     
     
         10 . The composition of  claim 9 , wherein said in situ formed polymer is present in a mammal or in a medical device located in the mammal in an intraluminal graft.  
     
     
         11 . The composition of  claim 10 , wherein in said intraluminal graft, said polymer is comprised of: 
 (a) di-(3-aminopropyl)diethylene glycol; and    (b) a mixture of polyethylene glycol glycidyl ether and trimethylolpropane triglycidyl ether.    
     
     
         12 . The composition of  claim 9 , wherein said in situ formed polymer is present in a mammal or in a medical device located in the mammal in an embolization device.  
     
     
         13 . The composition of  claim 12 , wherein said embolization device is comprised of: 
 (a) a mixture of di-(3-aminopropyl)diethylene glycol and polyoxyethylenediamine; and    (b) sorbitol polyglycidyl ether.    
     
     
         14 . The composition of  claim 12 , wherein said embolization device is comprised of: 
 (a) Di-(3-aminopropyl)diethylene glycol; and    (b) a mixture of pentaerythritol polyglycidyl ether and trimethylolpropane polyglycidyl ether.    
     
     
         15 . The composition of  claim 9 , wherein said in situ formed polymer is present in a mammal or in a medical device located in the mammal as an inflatable occlusion member or as a tissue bulking device.  
     
     
         16 . The composition of  claim 15 , wherein in said inflatable occlusion member or as a tissue bulking device, said polymer is comprised of: 
 (a) di-(3-aminopropyl)diethylene glycol; and    (b) sorbitol polyglycidyl ether.    
     
     
         17 . The composition of  claim 2 , wherein said diamine is present in an amount of between about 4 to about 20 weight percent of said polymer; and said polyglycidyl ether is present in an amount of between about 15 to about 60 weight percent of said polymer.  
     
     
         18 . The composition of  claim 2 , wherein said diamine is present in an amount of between about 5 to about 15 weight percent of said polymer; and said polyglycidyl ether is present in an amount of between about 25 to about 40 weight percent of said polymer.  
     
     
         19 . The composition of claims  2 ,  17 - 18 , wherein said diamine is di-(3-aminopropyl)diethylene glycol; said polyglycidyl ether is a mixture of polyethylene glycol glycidyl ether and trimethylolpropane triglycidyl ether; and said radiopaque material is selected from the group consisting of sodium iodide, potassium iodide, barium sulfate, Visipaque 320, Hypaque, Omnipaque 350 and Hexabrix.  
     
     
         20 . The composition of claims  2 ,  17 - 18 , wherein said diamine is di-(3-aminopropyl)diethylene glycol; said polyglycidyl ether is sorbitol polyglycidyl ether; and said radiopaque material is selected from the group consisting of sodium iodide, potassium iodide, barium sulfate, Visipaque 320, Hypaque, Omnipaque 350 and Hexabrix.  
     
     
         21 . The composition of  claim 2 , wherein said diamine is present in an amount of between about 7 to about 60 weight percent of said polymer; said polyglycidyl ether is present in an amount of between about 7 to about 55 weight percent of said polymer.  
     
     
         22 . The composition of  claim 2 , wherein said diamine is present in an amount of between about 10 to about 45 weight percent of said polymer; said polyglycidyl ether is present in an amount of between about 14 to about 35 weight percent of said polymer.  
     
     
         23 . The composition of  claim 2 , wherein said diamine is present in an amount of between about 5 to about 30 weight percent of said polymer; said polyglycidyl ether is present in an amount of between about 40 to about 90 weight percent of said polymer  
     
     
         24 . The composition of claims  2 ,  21 - 22 , wherein said diamine is selected from the group consisting of di-(3-aminopropyl)diethylene glycol and polyoxyethylenediamine; said polyglycidyl ether is sorbitol polyglycidyl ether; and said radiopaque material is selected from the group consisting of sodium iodide, potassium iodide, barium sulfate, Visipaque 320, Hypaque, Omnipaque 350 and Hexabrix.  
     
     
         25 . A kit for preparing an in situ hydrogel polymer composition of claims  1 - 24  comprising: 
 (a) a container with a first amount of a diamine;    (b) a container with a second amount of a polyglycidyl ether;    (c) optionally, a radiopaque material; and    instructions for combining the materials present in each of said containers to produce said hydrogel polymer in situ in a mammal or in a medical device located in a mammal.    
     
     
         26 . A method of forming a hydrogel polymer composition of claims  1 - 24 , said method comprising: 
 (1) forming a mixture comprising a diamine and a polyglycidyl ether;    (2) depositing said mixture in a mammal or into a medical device located in a mammal; and    (3) allowing said mixture to cure and form said hydrogel polymer composition.