Synthesis and properties of dextran-5-aminosalicylic acid ester as a potential colon-specific prodrug of 5-aminosalicylic acid.

Abstract

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.

• Authors: Y J Jung, J S Lee, H H Kim, Y T Kim, Y M Kim
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 21 Issue 2 Pg. 179-86 (Apr 1998) ISSN: 0253-6269 [Print] Korea (South)
• PMID: 9875428 (Publication Type: Journal Article)

Chemical References

• Aminosalicylic Acids
• Buffers
• Dextrans
• Prodrugs
• dextran-5-aminosalicylic acid
• Mesalamine

Topics

• Aminosalicylic Acids (chemical synthesis, pharmacokinetics)
• Animals
• Buffers
• Calibration
• Cecum (metabolism)
• Chromatography, High Pressure Liquid
• Colon (metabolism)
• Dextrans (chemical synthesis, pharmacokinetics)
• Gastric Mucosa (metabolism)
• Male
• Mesalamine (chemical synthesis, pharmacokinetics)
• Prodrugs (chemical synthesis, pharmacokinetics)
• Rats
• Rats, Sprague-Dawley
• Spectrophotometry, Ultraviolet