キトサンカプセルを用いた潰よう性大腸炎治療薬の大腸特異的送達法の開発

Abstract

Ulcerative colitis and Chrohn's disease are recurrent, idiopathic inflammatory disorders involving the mucosa and sub-mucosa of the colon. The objective of this study was to estimate colon-specific delivery of anti-ulcerative colitis drugs with chitosan capsules. Release studies of 5-aminosalicylic acid (5-ASA) from chitosan capsules were carried out by the Japan Pharmacopoeia (JP) rotating basket method with some slight modifications. There is no release of 5-ASA from chitosan capsules in the phosphate buffered saline, however the release of 5-ASA was markedly increased in the presence of rat cecal contents. The mucosal tissue concentrations of 5-ASA in the large intestine after oral administration using chitosan capsules were higher than those in the CMC suspension. The concentrations of 5-ASA in the contents of the large intestine, large intestinal tissue mucosa, and the plasma were determined by HPLC. Furthermore, the anti-inflammatory drugs were orally administered using chitosan capsules or a carboxymethyl cellulose sodium salt(CMC) suspension to trinitrobenzenesulfonic acid sodium salt (TNBS)-induced rats. The colonic injury and inflammation were assessed by measuring the myeloperoxidase (MPO) activities, the ratios of distal colon wet weight to body weight (C/B ratio) and the damage score. When 5-ASA was orally administered using chitosan capsules in TNBS-induced colitis rats, we found better therapeutic effects with 5-ASA than with a 5-ASA CMC suspension. Therefore, chitosan capsules may be useful carriers for the colon-specific delivery of anti-inflammatory drugs.