【作者】 刘静；

【导师】 刘皋林；

【作者基本信息】 第二军医大学 ， 药理学， 2005， 硕士

【摘要】 菌群触发型结肠释药系统(bacterially triggered colon specific drug delivery system,BCDDS)系利用大量细菌集中分布在结肠并分泌独特的偶氮还原酶、糖苷酶及糖苷酸酶等多种酶可降解特殊键的特点制备的口服释药系统,使药物在结肠定位释放,可避免药物在上消化道释放引起的副作用和消化酶对药物的破坏,是一种较为理想的靶向释药触发机制。 5-氨基水杨酸(5-aminosalicylic acid, 5-ASA)是治疗溃疡性结肠炎、克隆氏病的有效药物,不良反应较少,主要为胃肠道刺激和肾毒性。临床上多数炎性肠病的病变主要发生在回肠末段和结肠,所以治疗中要求5-ASA在回肠末段和结肠腔内有较高的药物浓度。5-ASA仅以原形在结肠病变部位发挥作用,由于其易在胃肠道上部吸收,因此一般的口服制剂给药后极少有原形5-ASA到达结肠部位,使得5-ASA的治疗效果不理想。尽管国内外已经有几种5-ASA口服制剂上市,但都是缓释制剂或肠溶包衣制剂,都有结肠定位差的缺点,而国内尚无国产5-ASA制剂上市。因此,研究5-ASA结肠靶向释药系统有重要意义。 本课题利用壳聚糖在小肠溶胀而不溶解、在结肠可被特异酶降解的特点,以壳聚糖和丙烯酸树脂(L100-55)包衣5-ASA片芯,制备口服5-ASA结肠靶向片,并对其体内外释放及药效学进行研究。 将不同的填充剂、崩解剂、粘合剂、润滑剂湿法制粒,压片,以崩解时限作为考察指标进行处方设计和优化。结果显示微晶纤维素做填充剂、交联PVP 5%、10%PVP 50%乙醇/水、滑石粉5%,崩解最快(197秒),溶出完全,故采用此处方制备片芯。 考察不同壳聚糖浓度(1%、2%、3%),包衣增重(1%、2%、3%),增塑剂种类(邻苯二甲酸二乙酯、柠檬酸三乙酯、甘油三醋酸脂)、增塑剂用量(10%、20%、30%)的条件下,片子在pH6.8模拟小肠液和在pH7.0模拟结肠液中的溶出度。结果显示壳聚糖浓度、包衣增重、增塑剂用量对溶出度影响较大。筛选出合适的增塑剂邻苯二甲酸二乙酯,用量20%,确定壳聚糖浓度2%,包衣增重2%。更多还原

【Abstract】 Colon, as a site offers distinct advantages on account of a near neutral pH, a much longer transit time, reduced digestive enzymatic activity and a much greater responsiveness to absorption enhancers. This enables the visualization of this distal part of GIT as a site for delivery of various drug molecules including proteins and peptides. Bacterially triggered colon specific drug delivery system (BCDDS) is using the existing of micro flora to preparation oral colon-specific drug delivery system OCDDS. For local pathologies of colon specific drug deliver, not only increase the bioavailability of drug at the target site, reduce the dose to be administered but also would reduce the side effects.5-aminosalicylic acid (5-ASA) is an important drug treating IBD, including Ulcerative Colon and Crohn’s Disease. The major side effect is the stimulation to stomach and small intestine. The active form of 5-ASA to treat IBD is its original shape. But the absorption in the upper GIT will bring the side effect and deactivate the 5-ASA. Several OCDDSs have been coming into the market in the overseas, however they all have the disadvantage that a substantial amount of drug may be released in the small intestine before the delivery system arrives in the colon. There have no domestic 5-ASA preparation came into market. So the study on the 5-ASA colon specific delivery system is of great significance.In this article we use the new colon digested material chitosan film as a coat to protect 5-ASA tablet from the releasing in the small intestine and the Eudragit L100-55 as the enteric coat, meanwhile study the pharmacodynamics and the release profiles of 5-ASA in vitro and in vivo.MicroCellulosePH101 ( filling agent ) PVPP(disintegration agent) PVP K30(binding agent)have been mixed, wet-grained and prepared into tablets. The disintegration time was used as the index to evaluate the factors and Rx. The results showed that the best Rx is the pvpp5% 10%pvp50%ethanol/H2O talcum powder 5% and the disintegration time is 197s.更多还原