【作者】 薛梅；

【导师】 高晓黎； 斯拉甫；

【作者基本信息】 新疆医科大学 ， 药剂学， 2008， 硕士

【摘要】 目的:我国UC的发病率近年呈上升趋势,已引起医药行业人士的广泛重视。“溃结安灌肠液”在新疆维吾尔医医院临床使用多年,对溃疡性结肠炎疗效显著,但该剂型应用不便,制约了药效发挥,结合UC的治疗需求,本课题旨在将其改为口服结肠靶向给药系统(OCTDS),以提高该药疗效和患者顺应性。方法:(1)首先进行了口服急性毒性试验的研究,为药效学、制剂学及后续工作提供剂量参考依据。随后,建立大鼠溃疡性结肠炎的模型动物,再分别给予溃结安(高、低剂量组),以柳氮磺吡啶肠溶片为阳性对照,观察各组大鼠结肠形态学变化,通过结肠组织损伤评分、测定肠重指数、免疫器官相对重量、大鼠血清中炎性细胞因子MPO、SOD活性及病理切片来观察该药的初步药效。(2)通过对制剂成型工艺、临界相对湿度考察、胶囊包衣处方三方面的研究,制备溃结安pH依赖型和pH依赖-时滞型结肠靶向包衣胶囊。为评价该制剂,建立了游离没食子酸的HPLC含量测定方法,以此为指标进行体外溶出实验,并且以硫酸钡造影技术观察犬口服该制剂后的体内释放情况。结果:(1)小鼠对溃结安的最大耐受倍数为人的833倍。溃结安低剂量组的治疗作用与阳性药组有差异,溃结安高剂量组与其无显著差异。(2)通过将药物制粒后,灌装于胶囊再包衣的工艺路线可得到pH依赖型和pH依赖-时滞型结肠靶向包衣胶囊,前者工艺相对简单,可操作性强。该胶囊在人工胃液、人工肠液几乎不释放,在人工结肠液中1h累积释放达到104%。犬消化道X射线照片清晰可见该胶囊在犬的结肠部位释放。结论:(1)没食子提取物毒性小,安全系数大,口服该药对TNBS所致UC大鼠有明确的治疗作用。(2)通过胶囊包衣制备得到的pH依赖型结肠靶向胶囊在体内外均有较好的释药性能。(3)该制剂工艺的研究,合理可行,在改进传统临床治疗UC给药方式的同时推动了中药、民族药制剂研究水平的提高。更多还原

【Abstract】 Object: In recent years ,disease incidence of UC is upgrading in China,this arise high attention of many from medicine vocation. Kuijiean enema was used many years in Xinjiang Uighur hospital,which has conspicuous clinical effect. But this dosage form is inconvenience and restricted in application,so we change it into OCTDS in order to raise its therapeutics effect and lessen the patient’s painful. Methods: 1)First of all,we progressed acute noxious experiment for oral use,which provided reference evidence for pharmacodynamics and galenic pharmacy. In this base on,a rat model of UC was induced by TNBS/ethanol in order to evaluate the effects of KJA. The microscopically and microscopically examination of the colon was detected. The immune organic relative weights were menstruated to imply the change of immune functions in rats. The activity of SOD and MPO were detected. 2)During the study of form selecting,forming and coating artwork, pH depended type colon target preparations of KJA and pH depended-time lagged type ones were acquired.AHPLC method was established in vitro dissolution determination for preparations. And the releasing site and time of the drugs from the colon-specific coated capsule in dogs were screened by X scintigraphy. Results: 1)The maximum tolerated doseof mouse is 833 times than that of man. The high doge group of KJA has appositive therapeutic effect to UC. 2)The molding techniques of pH depended type colon target preparations of KJA and pH depended-time lagged type ones were researched. The former is more simply and operability.At last,the results of authentication show that KJA colon-specific coated capsule had the colon targeting characteristics in vitro and vivo. Conclusion: This research identified Turkish galls medicinal have a small noxious and obviously therapeutic effect by oral. Exploitation of this medicine not only changed traditional administration mode for UC and elevated the level of Chinese ethical medicine’s research.更多还原