Polymer Hydrogels and Methods of Preparation Thereof

Abstract

The invention relates to a method for the preparation of a polymer hydrogel, comprising cross-linking a precursor comprising a hydrophilic polymer optionally in combination with a second hydrophilic polymer, using a polycarboxylic acid as the cross-linking agent. The invention further concerns the polymer hydrogel obtainable by the method of the invention and the use thereof in a number of different applications.

1 - 51 . (canceled) 
     
     
         52 . A method of treating obesity in a subject in need thereof, comprising orally administering to the subject an effective amount of a hydrogel comprising a hydrophilic polymer which is crosslinked with a polycarboxylic acid. 
     
     
         53 . The method of  claim 52 , wherein the hydrophilic polymer is a polysaccharide. 
     
     
         54 . The method of  claim 53 , wherein the polysaccharide is ionic. 
     
     
         55 . The method of  claim 53 , wherein the polysaccharide is selected from the group consisting of hydroxyethylcellulose, hydroxy-n-propylcellulose, hydroxy-n-butylcellulose, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose, carboxymethylcellulose, hydroxypropylstarch, carboxymethyl starch; dextran sulfate, dextran phosphate, diethylaminodextran, heparin, hyaluronan, chondroitin, chondroitin sulfate, heparan sulfate, polyglucuronic acid, polymanuronic acid, polygalacturonic acid and polyarabinic acid. 
     
     
         56 . The method of  claim 54 , wherein the polysaccharide is selected from the group consisting of alginate, dextran sulfate, carboxymethylcellulose, hyaluronic acid, polyglucuronic acid, polymanuronic acid, polygalacturonic acid, polyarabinic acid; chrondroitin sulfate, dextran phosphate, chitosan and dimethylaminodextran. 
     
     
         57 . The method of  claim 52 , wherein the polycarboxylic acid is a dicarboxylic acid, a tricarboxylic acid or a tetracarboxylic acid. 
     
     
         58 . The method of  claim 57 , wherein the polycarboxylic acid is selected from the group consisting of oxalic acid, malonic acid, maleic acid, malic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, phthalic acid, o-phthalic acid, isophthalic acid, m-phthalic acid, terephthalic acid, citric acid, isocitric acid, aconitic acid, propane-1,2,3-tricarboxylic acid, pyromellitic acid, 2,3,3′,4′-biphenyltetracarboxylic acid, 3,3′,4,4′-tetracarboxydiphenylether, 2,3′,3,4′-tetracarboxydiphenylether, 3,3′,4,4′-benzophenonetetracarboxylic acid, 2,3,6,7-tetracarboxynaphthalene, 1,4,5,7-tetracarboxynaphthalene, 1,4,5,6-tetracarboxynaphthalene, 3,3′,4,4′-tetracarboxydiphenylmethane, 2,2-bis(3,4-dicarboxyphenyl)propane, butanetetracarboxylic acid, and cyclopentanetetracarboxylic acid. 
     
     
         59 . A method of reducing calorie intake by a subject in need thereof, comprising orally administering to the subject an effective amount of a hydrogel comprising a hydrophilic polymer which is crosslinked with a polycarboxylic acid. 
     
     
         60 . The method of  claim 59 , wherein the hydrophilic polymer is a polysaccharide. 
     
     
         61 . The method of  claim 60 , wherein the polysaccharide is ionic. 
     
     
         62 . The method of 60, wherein the polysaccharide is selected from the group consisting of hydroxyethylcellulose, hydroxy-n-propylcellulose, hydroxy-n-butylcellulose, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose, carboxymethylcellulose, hydroxypropylstarch, carboxymethyl starch; dextran sulfate, dextran phosphate, diethylaminodextran, heparin, hyaluronan, chondroitin, chondroitin sulfate, heparan sulfate, polyglucuronic acid, polymanuronic acid, polygalacturonic acid and polyarabinic acid. 
     
     
         63 . The method of  claim 61 , wherein the polysaccharide is selected from the group consisting of alginate, dextran sulfate, carboxymethylcellulose, hyaluronic acid, polyglucuronic acid, polymanuronic acid, polygalacturonic acid, polyarabinic acid; chrondroitin sulfate, dextran phosphate, chitosan and dimethylaminodextran. 
     
     
         64 . The method of  claim 59 , wherein the polycarboxylic acid is a dicarboxylic acid, a tricarboxylic acid or a tetracarboxylic acid. 
     
     
         65 . The method of  claim 64 , wherein the polycarboxylic acid is selected from the group consisting of oxalic acid, malonic acid, maleic acid, malic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, phthalic acid, o-phthalic acid, isophthalic acid, m-phthalic acid, terephthalic acid, citric acid, isocitric acid, aconitic acid, propane-1,2,3-tricarboxylic acid, pyromellitic acid, 2,3,3′,4′-biphenyltetracarboxylic acid, 3,3′,4,4′-tetracarboxydiphenylether, 2,3′,3,4′-tetracarboxydiphenylether, 3,3′,4,4′-benzophenonetetracarboxylic acid, 2,3,6,7-tetracarboxynaphthalene, 1,4,5,7-tetracarboxynaphthalene, 1,4,5,6-tetracarboxynaphthalene, 3,3′,4,4′-tetracarboxydiphenylmethane, 2,2-bis(3,4-dicarboxyphenyl)propane, butanetetracarboxylic acid, and cyclopentanetetracarboxylic acid.