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

(1)制备抗炎作用强、全身副反应低的二丙酸倍氯米松（BDP），并对该灌肠剂在溃疡性结肠炎患者的临床应用进行药学研究。将BDP乙醇加入1%甲基纤维素的水溶液中制备灌肠剂。这些灌肠剂（n=6），在4‰冷藏条件下保存，与制备后立即确定的浓度相比，一周内BDP的平均残留浓度下降到93.4%，四周内下降到85.6%。在40ºC的光照下，BDP灌肠剂的残留浓度在1周内下降到93.9%，此后基本保持不变，但在制备后第1天观察到BDP的结晶。在灌肠液中加入对羟基苯甲酸甲酯可提高BDP的稳定性。应用BDP灌肠治疗溃疡性结肠炎3例。在临床症状和血液数据（与炎症有关的值：白细胞和c反应蛋白）方面，所有三个亚…另外，在使用强的松龙灌肠后出现月相脸和水肿等副作用的2例患者中，经BDP灌肠后，副作用消失。已有研究表明BDP灌肠治疗溃疡性结肠炎有效。(2)通过对2,4,6 -三硝基苯磺酸（TNB）诱导的炎性肠病Fischer雄性大鼠给予BDP灌肠剂，观察BDP灌肠剂对溃疡性结肠炎的治疗作用。在TNB治疗3天后的4天或11天内，每天给大鼠一次BDP灌肠，剂量为20或50马克杯。BDP给药后，与未给药大鼠相比，大鼠腹泻和黑黑的发生率随时间的推移而降低，给药后第4天所有大鼠的症状均得到改善。在早期（第4天）发现湿组织重量和损伤分数的剂量依赖性恢复以及组织中的mycloperoxidase （MPO）活性。然而，他们在每剂量BDP的第11天的测量结果与对照组没有显著差异，因为对照组的结肠损伤随着时间的推移自然恢复。通过阐明TNB致炎性肠病模型大鼠早期剂量依赖性，支持BDP灌肠剂的临床应用价值。少

(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