5-아미노살리실산의 결장표적성 프로드럭 : 5-아미노살리실-L-글루타민산과 5-아미노살리실-L-아스파틸산의 합성 및 성상

Synthesis and Properties of 5-Aminosalicyl-L-Aspartic Acid and 5-Aminosalicyl-L-glutamic Acid as Colon-specific Prodrugs of 5-Aminosalicylic Acid

5-Aminosalicyl-L-aspartic acid (5-ASA-Asp) and 5-aminosalicyl-L-glutamic acid (5-ASA-Glu) were synthesized as new colon-specific prodrugs of 5-aminosalicylic acid (5-ASA), their apparent partition coefficients, and the extent of conversion in the homogenates of tissue and contents of various G.I. Tract segments of rats were evaluated. These prodrugs were stable in the homogenate of tissue and contents of stomach, proximal small intestine (PSI) or distal small intestine (DSI). Release of 5-ASA from 5-ASA-Asp after incubation with the cecal and colonic contents for 8hrs at 37oC was 18%, and 8%, respectively. No significant conversion of prodrug was observed in the cecal and colonic contents of rats pretreated with kanamycin sulfate, which indicated that microbial enzymes were responsible for the cleavage of these prodrugs.