Ingestible formulations for transient, noninvasive reduction of gastric volume

Abstract

Provided are ingestible polymeric formulations for the reduction of gastric volume in the treatment of overweight patients, and methods of use thereof. One method involves ingesting one or more ingestible tablets comprising cross-linked polymers formed in a packed mass within the one or more ingestible tablets into a stomach of the subject, wherein the cross-linked polymers comprise a polymer hydrogel comprising carboxymethylcellulose and a carboxylic acid; disintegrating an acid-sensitive gelatin coating such that the coating disintegrates in the gastric fluid and the cross-linked polymers disperse in the stomach; and maintaining the reduction in gastric volume such that a sensation of fullness is induced in the subject without releasing a drug which induces the sensation.

We claim: 
     
         1 . A method of treating obesity in a subject in need thereof, comprising:
 ingesting one or more ingestible tablets comprising cross-linked polymers formed in a packed mass within the one or more ingestible tablets into a stomach of the subject,
 wherein the cross-linked polymers comprise a polymer hydrogel comprising carboxymethylcellulose and a carboxylic acid; 
   disintegrating an acid-sensitive gelatin coating such that the coating disintegrates in the gastric fluid and the cross-linked polymers disperse in the stomach, wherein the cross-linked polymers are configured to swell upon absorbing at least one of water and gastric fluid to increase in size and reduce a gastric volume of the stomach of the subject; and   maintaining the reduction in gastric volume such that a sensation of fullness is induced in the subject without releasing a drug which induces the sensation.   
     
     
         2 . The method of  claim 1 , wherein the polymer hydrogel further comprises hydroxyethylcellulose. 
     
     
         3 . The method of  claim 1 , wherein the cross-linked polymers are dehydrated when formed in the packed mass within the one or more ingestible tablets. 
     
     
         4 . The method of  claim 1 , wherein the cross-linked polymers are shaped as particles when formed in the packed mass within the one or more ingestible tablets such that the particles disperse when the coating disintegrates. 
     
     
         5 . The method of  claim 1 , wherein the carboxymethylcellulose is cross-linked with the carboxylic acid. 
     
     
         6 . The method of  claim 1 , wherein the cross-linked polymers are cross linked using a cross-linker which provides the polymers with a degradation susceptibility towards an intestinal enzyme or an intestinal pH. 
     
     
         7 . The method of  claim 6 , wherein the intestinal enzyme is selected from the group consisting of lipase, amylase, trypsin, chymotrypsin, elastase, carboxypeptidase, nucleases, aminopeptidases, disaccharidases, maltase, sucrose, and lactase. 
     
     
         8 . The method of  claim 1 , wherein the cross-linked polymers degrade faster in an environment with intestinal pH than an environment with gastric pH. 
     
     
         9 . The method of  claim 1 , wherein the cross-linked polymers are configured to maintain their physical integrity when swollen upon absorbing the at least one of water and gastric fluid such that the cross-links remain substantially intact and provide a three-dimensional polymeric network. 
     
     
         10 . The method of  claim 9 , wherein the cross-linked polymers are configured to maintain their physical integrity for at least two hours. 
     
     
         11 . An oral dosage form to treat obesity in a subject in need thereof, comprising:
 one or more ingestible tablets comprising cross-linked polymers formed in a packed mass within the one or more ingestible tablets, wherein the cross-linked polymers comprise a polymer hydrogel comprising carboxymethylcellulose and a carboxylic acid; and   an acid-sensitive gelatin coating covering the one or more ingestible tablets, wherein the coating is configured to disintegrate in the gastric fluid, wherein the cross-linked polymers are configured to disperse in the stomach, and wherein the cross-linked polymers are configured to swell upon absorbing at least one of water and gastric fluid to increase in size and reduce a gastric volume of the stomach of the subject such that a sensation of fullness is induced in the subject without releasing a drug which induces the sensation.   
     
     
         12 . The oral dosage form of  claim 11 , wherein the polymer hydrogel further comprises hydroxyethylcellulose. 
     
     
         13 . The oral dosage form of  claim 11 , wherein the cross-linked polymers are dehydrated when formed in the packed mass within the one or more ingestible tablets. 
     
     
         14 . The oral dosage form of  claim 11 , wherein the cross-linked polymers are shaped as particles when formed in the packed mass within the one or more ingestible tablets such that the particles disperse when the coating disintegrates. 
     
     
         15 . The oral dosage form of  claim 11 , wherein the carboxymethylcellulose is cross-linked with the carboxylic acid. 
     
     
         16 . The oral dosage form of  claim 11 , wherein the cross-linked polymers are cross linked using a cross-linker which provides the polymers with a degradation susceptibility towards an intestinal enzyme or an intestinal pH. 
     
     
         17 . The oral dosage form of  claim 16 , wherein the intestinal enzyme is selected from the group consisting of lipase, amylase, trypsin, chymotrypsin, elastase, carboxypeptidase, nucleases, aminopeptidases, disaccharidases, maltase, sucrose, and lactase. 
     
     
         18 . The oral dosage form of  claim 11 , wherein the cross-linked polymers degrade faster in an environment with intestinal pH than an environment with gastric pH. 
     
     
         19 . The oral dosage form of  claim 11 , wherein the cross-linked polymers are configured to maintain their physical integrity when swollen upon absorbing the at least one of water and gastric fluid such that the cross-links remain substantially intact and provide a three-dimensional polymeric network. 
     
     
         20 . The oral dosage form of  claim 11 , wherein the cross-linked polymers are configured to maintain their physical integrity for at least two hours.