Colon-specific delivery of R68070, a new thromboxane synthase inhibitor, using chitosan capsules: therapeutic effects against 2,4,6-trinitrobenzene sulfonic acid-induced ulcerative colitis in rats.
The objective of this study was to estimate the therapeutic effects of R68070, a new thromboxane synthase inhibitor, on 2,4,6-trinitrobenzenesulfonic acid sodium salt (TNBS)-induced ulcerative colitis in rats. We also examined the acceleration of the healing effect of R68070 with chitosan capsules to achieve its colon-specific delivery. The colonic injury and inflammation were assessed by measuring the myeloperoxidase (MPO) activities, colon wet weight/body weight (C/B) ratio and the damage score, respectively. These markers were decreased by the oral administration of R68070 with chitosan capsules and carboxymethyl-cellulose (CMC) suspension. The therapeutic effects of R68070 against ulcerative colitis were observed in both dosage forms in a dose dependent manner. In addition, its therapeutic effects were increased by the use of chitosan capsules, compared with CMC suspension. These results suggest that chitosan capsule might be a very useful dosage form for the colon-specific delivery of R68070 as an anti-inflammatory drug and for the therapy of ulcerative colitis.
Tozaki
H
H
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Fujita
T
T
Odoriba
T
T
Terabe
A
A
Suzuki
T
T
Tanaka
C
C
Okabe
S
S
Muranishi
S
S
Yamamoto
A
A
D000818:Animals; D002214:Capsules; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D048271:Chitosan; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects*; D008297:Male; D010421:Pentanoic Acids / Q000008:administration & dosage*; D009195:Peroxidase / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014302:Trinitrobenzenesulfonic Acid
D002214:Capsules; D010421:Pentanoic Acids; D011725:Pyridines; D002686:Chitin; D014302:Trinitrobenzenesulfonic Acid; D048271:Chitosan; D009195:Peroxidase; D013930:Thromboxane-A Synthase; C060219:ridogrel