Development and Clinical Use of Beclomethasone dipropionate Preparations for the Purpose of Treatments of Ulcerative Colitis Patients

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(1) Beclomethasone dipropionate (BDP), with a strong anti-inflammatory action and low systemic side effects, was prepared and a pharmaceutical study of this enema was performed for the clinical application of ulcerative colitis patients. Enemas were prepared by adding BDP ethanol to an aqueous solution of 1 % methylcellose. The mean residual concentration of BDP in these enemas (n=6), preserved in dark under refrigeration at 4 ﾟC declined to 93.4% in one week and 85.6% in four weeks, when compared to the concentration decided immediately after preparation. Although the residual concentration of BDP enemas, preserved in light at 40 ﾟC, declined to 93.9% in one week and remained almost constant thereafter, crystallization of BDP was observed the first day after preparation. The stability of BDP in enemas was improved by adding methyl p-hydroxybenzoate to these solutions. Theses BDP enemas were administered to three patients with ulcerative colitis. Improvements were seen in all three sub … More jects, in terms of both clinical symptoms and blood data (values related to inflammatory : white blood cells and C-reactive protein). Also the disappearance of side effects were confirmed after administration of BDP enemas in two of the subjects who had developed side effects such as moon face arid edema with predonisolone enemas. It has been suggested that BDP enemas are efficacious in the treatment of ulcerative colitis.(2) The effects of BDP enemas to ulcerative colitis were investigated by administrating BDP enemas to Fischer male rats with inflammatory bowel disease induced by 2, 4, 6-trinitrobenzensulfonic acid (TNB). BDP enemas were administrated to rats one time a day at a dose of 20 or 50 mug of BDP during 4 or 11 days from 3 days after TNB treatment. After BDP dosing, the rate of rats occurring diarrhea and melena was decreased in comparison with BDP free rats with time, and their symptoms of all rats were improved the day 4 at the dose of 50 mug of BDP.A dose dependent recovery in the wet tissue weights and scores of damage, and the mycloperoxidase (MPO) activity in the tissue were found at the early days (the day 4). However, their measurements the day 11 at the each dose of BDP were not different from control significantly, as colon damages of control were recovered naturally with time. The clinical usefulness of BDP enemas was supported by elucidating the dose dependent effect at the early days in the model rats with inflammatory bowel disease induced by TNB. Less