SYNTHESIS AND INTESTINAL METABOLISM OF URSODEOXYCHOLIC ACID CONJUGATEWITH AN ANTIINFLAMMATORY AGENT, 5-AMINOSALICYLIC ACID

5-Aminosalicylic acid conjugate of ursodeoxycholic acid was synthesize d in above 90% yield by adding a basic solution of 5-aminosalicylic ac id into the mixed anhydride formed with ursodeoxycholic acid and ethyl chloroformate. The 5-aminosalicylic acid conjugate of ursodeoxycholic acid was poorly secreted into the bile and was deconjugated with chol ylglycine hydrolase and Clostridium perfringens, that deconjugate natu rally occurring glycine and taurine conjugates of bile acids, However, ursodeoxycholic acid 5-aminosalicylic acid conjugate was not absorbed from the duodenum but was concentrated in the colon where it was part ially hydrolyzed by the intestinal bacteria to ursodeoxycholic acid an d 5-aminosalicylic acid. We believe that this unique conjugation of ur sodeoxycholic acid with 5-aminosalicylic acid may facilitate the trans port of both 5-aminosalicylic acid and ursodeoxycholic acid to the col on and may be useful for the treatment of colonic inflammatory bowel d iseases, ulcerative colitis and Crohn's disease.