Sustained-release chitosan capsules comprising chitosan and phytic acid

Abstract

The present invention relates to a chitosan capsule in which a soluble active ingredient is encapsulated in a matrix containing chitosan and phytic acid; a cross-linking method and materials capable of being used in preparing the capsule; and pharmaceutical, food and cosmetic compositions comprising the capsule. The chitosan capsule according to the present invention is prepared via ionic gelation of chitosan as a biodegradable polymer with phytic acid capable of rapidly and effectively forming a cross-linking reaction with the chitosan polymer. The capsule of the present invention shows high encapsulation efficiency for a soluble active ingredient and protects the soluble active ingredient from being damaged in a digestive tract, resulting in improving an in vivo delivery efficiency of a physiologically active material. Further, since the capsule of the present invention has a pH-dependent sustained-release mechanism which can minimize the release of a soluble active ingredient in the stomach and gradually release in the intestine, it is possible to regulate sustained-release of a soluble active ingredient.

1 . A chitosan capsule comprising a soluble active ingredient encapsulated within a matrix containing chitosan and phytic acid. 
     
     
         2 . The chitosan capsule as claimed in  claim 1 , wherein the soluble active ingredient is one or more ingredients selected from the group consisting of a pharmaceutically active ingredient, a food active ingredient and a cosmetically active ingredient. 
     
     
         3 . The chitosan capsule as claimed in  claim 2 , wherein the soluble active ingredient is one or more ingredients selected from the group consisting of a nucleic acid, an amino acid, a peptide, a protein, a sugar, a carbohydrate, a lipid, a glycolipid, a plant-, animal- or microorganism-derived compound, a plant extract, a synthetic compound, a vitamin, a microorganism and a virus. 
     
     
         4 . The chitosan capsule as claimed in  claim 1 , wherein the chitosan is one or more components selected from the group consisting of poly[β-(1-4)-2-amino-2-dioxy-D-glucopyranoseb thiolated chitosan, trimethylated chitosan, carboxymethyl chitosan and N-(2-hydroxyl propyl-3-trimethyl ammonium) chitosan chloride. 
     
     
         5 . The chitosan capsule as claimed in  claim 1 , wherein the chitosan has an average molecular weight ranging from 30,000 to 1,000,000 daltons. 
     
     
         6 . A method of cross-linking biocompatible polymers using phytic acid. 
     
     
         7 . The method as claimed in  claim 6 , wherein the biocompatible polymer is cationic. 
     
     
         8 . The method as claimed in  claim 7 , wherein the biocompatible polymer is chitosan. 
     
     
         9 . A method of preparing a chitosan capsule comprising:
 a first step of preparing an aqueous solution containing chitosan and a soluble active ingredient;   a second step of preparing an aqueous solution containing phytic acid; and   a third step of bringing the aqueous solution prepared in the first step into contact with the aqueous solution prepared in the second step to perform ionic gelation.   
     
     
         10 . The method as claimed in  claim 9 , wherein the first step comprises:
 (a) preparing a chitosan aqueous solution by adding chitosan to an aqueous solution;   (b) preparing a soluble active ingredient aqueous solution; and   (c) mixing the chitosan aqueous solution with the soluble active ingredient aqueous solution.   
     
     
         11 . The method as claimed in  claim 10 , wherein the chitosan aqueous solution of step (a) comprises a weak acid at a concentration ranging from 0.01 to 20% (w/v). 
     
     
         12 . The method as claimed in  claim 11 , wherein the weak acid is one or more acids selected from the group consisting of acetic acid, lactic acid, citric acid, formic acid, ascorbic acid, oxalic acid, dilute hydrochloric acid and dilute sulfuric acid. 
     
     
         13 . The method as claimed in  claim 10 , wherein the chitosan aqueous solution of step (a) comprises chitosan at a concentration ranging from 0.01 to 50% (w/v). 
     
     
         14 . The method as claimed in  claim 10 , wherein the soluble active ingredient aqueous solution of step (b) comprises a soluble active ingredient at a concentration of 0.01% (w/v) or more. 
     
     
         15 . The method as claimed in  claim 9 , wherein the phytic acid aqueous solution of the second step has a pH ranging from 0.5 to 7. 
     
     
         16 . The method as claimed in  claim 15 , wherein the phytic acid aqueous solution of the second step has a pH ranging from 1 to 6. 
     
     
         17 . The method as claimed in  claim 9 , wherein the phytic acid aqueous solution of the second step comprises phytic acid at a concentration of 0.1% (w/v) or more. 
     
     
         18 . The method as claimed in  claim 17 , wherein the phytic acid aqueous solution of the second step comprises phytic acid at a concentration of 2% (w/v) or more. 
     
     
         19 . The method as claimed in  claim 9 , wherein the contact of the third step is carried out by adding the aqueous solution of the first step to the aqueous solution of the second step in a dropping manner. 
     
     
         20 . The method as claimed in  claim 9 , which further comprises at least one step selected from the group consisting of separating the chitosan capsule prepared in the third step, and washing and drying the same. 
     
     
         21 . The method as claimed in  claim 20 , wherein the drying step is performed by freeze-drying. 
     
     
         22 . A pharmaceutical composition comprising the chitosan capsule according to any one of  claims 1  to  7  and a pharmaceutically acceptable carrier. 
     
     
         23 . The pharmaceutical composition as claimed in  claim 22 , wherein the chitosan capsule comprises albumin, insulin or growth hormone as the soluble active ingredient. 
     
     
         24 . A food composition comprising the chitosan capsule according to any one of  claims 1  to  7  and a food additive. 
     
     
         25 . A cosmetic composition comprising the chitosan capsule according to any one of  claims 1  to  7  and a cosmetic additive.