Synthesis and properties of dextran-5-aminosalicylic acid ester as a potential colon-specific prodrug of 5-aminosalicylic acid.
Dextran-5-aminosalicylic acid ester (dextran-5-ASA) was synthesized as a colon-specific prodrug of 5-aminosalicylic acid (5-ASA) which is active against inflammatory bowel diseases. Chemical stability of dextran-5-ASA in the bath of pH 1.2 or 6.8 was investigated at 37 degrees C for 6 hrs, and 5-ASA was not released on such conditions. Depolymerization (%) of dextran-5-ASA by dextranase with the degree of substitution (DS) of 18, 23, or 30 was 92, 62 or 45 in 8 hrs respectively, but was not affected by the MW of dextran (9,000, 40,600, 80,200 or 580,000). Distribution of 5-ASA in dextran, determined by gel filtration chromatography, appeared to be relatively uniform. Incubation of dextran-5-ASA (DS 18) in cecal contents of rats released 20% (28 g) and 35% (49 g) of 5-ASA in 8 hrs and 24 hrs, respectively, but no 5-ASA was liberated from small intestinal contents.
Jung
Y J
YJ
College of Pharmacy, Pusan National University, Korea.
Lee
J S
JS
Kim
H H
HH
Kim
Y T
YT
Kim
Y M
YM
D000636:Aminosalicylic Acids / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000818:Animals; D002021:Buffers; D002138:Calibration; D002432:Cecum / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000378:metabolism*; D003911:Dextrans / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D019804:Mesalamine / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet
D000636:Aminosalicylic Acids; D002021:Buffers; D003911:Dextrans; D011355:Prodrugs; C116886:dextran-5-aminosalicylic acid; D019804:Mesalamine