三种原理苦参结肠靶向微丸在大鼠体内转运及释药性能的对比研究

摘要

Objective To investigate the conveying and drug release in vivo of three different principal kinds of colon target pellets of Sophora flavescens in rats: pH-triggered-single-layer (I), pH-triggered-double-layer (II), pH-triggered and enzyme-triggering combination (III), and select the best scheme, and the best scheme will be selected.Methods The SD rats were randomly divided into four groups: the pellet core, colon target pellets I, II and III, three rats per time point each group. The four kinds of pellets were administered by stomach cannula. The rats were respectively killed and stomach, small intestine and colon tisses were harvested at 0.5, 1, 2 hour after administering the pellet core, and at 1, 2, 3, 4, 6, 8, 10, 12,16, 20, 24 hour after administering the three kinds of colon target pellets. The appearance of pellets were observed. The sum of pellets and the distribution rates in different sections of alimentary canal were counted. After the residue level of matrine and oxymatrine in pellets were respectively determined by HPLC, the accumulated drug release rates and the release index number of three kinds of target pellets in vivo after administration at different times were calculated.Results The gastric emptying of three kinds of target pellets all showed continual, all stayed transiently in small intestine and were transferred to colon completely. Compared with pellets model I and II, the pellet of model III was obviously prolonged in the gastric emptying, and obviously delayed to reach colon. Compared with the pellet core, the three kinds of target pellets all possessed the obvious delayed effects of drug release. The descending sequence of cumulated drug release rates of the three kinds of target pellets in stomach and small intestine was model III (34.5%) > model I (17.4%) > model II (11.8%). The descending sequence of cumulated drug release rates of the three kinds of target pellets in colon was model I (98.9%) > model II (97.7%) > model HI (91.7%). The descending sequence of the release index number of the three kinds of target pellets was model II (7.3) > model I (4.7) > model III (1.7).Conclusion Three different principal kinds of colon target pellets of Sophora flavescens all possessed the characteristic of colon target drug delivery, which of pH-triggered-double-layer (II) was the best.%目的 对比pH敏感单层型（Ⅰ型）、pH敏感双层型(Ⅱ型)、pH-酶触发双控型（Ⅲ型）3种原理苦参结肠靶向微丸在大鼠体内的转运及释药性能,并优选最佳方案.方法　按给药不同将SD大鼠随机分为4组:Ⅰ、Ⅱ、Ⅲ型苦参结肠靶向微丸组和苦参丸心组,每组每时间点各3只.通过胃插管给药,苦参丸心组分别于给药后0.5、1、2h,3种苦参结肠靶向微丸组分别于给药后1、2、3、4、6、8、10、12、16、20、24 h处死大鼠,剖取胃、小肠、结肠组织.观察微丸外观性状并计数,计算给药后不同时间点其在各段消化道的分布率;采用HPLC法测定微丸中苦参碱、氧化苦参碱的残留总量,计算给药后不同时间点其在体内的累积释放度和定位释约指数.结果　3种靶向微丸的胃排空均呈连续性,在小肠段短暂停留后即被完整转运至结肠；与Ⅰ、Ⅱ型微丸相比,Ⅲ型微丸胃排空时间明显延长,抵达结肠时间也明显延迟.相比于苦参丸心,3种靶向微丸均具有明显的迟释效应;3种靶向微丸在胃与小肠段的累积释放度由高至低依次为Ⅲ型(34.5％)＞Ⅰ型(17.4％)＞Ⅱ型(11.8％)；在结肠段的累积释放度由高至低依次为Ⅰ型(98.9％)＞Ⅱ型(97.7％)＞Ⅲ型(91.7％);3种靶向微丸的定位释药指数分别为4.7、7.3、1.7,定位释药性能由高至低依次为Ⅱ型＞Ⅰ型＞Ⅲ型.结论　3种原理苦参结肠靶向微丸均具有结肠定位释药性能,其中pH敏感双层型（Ⅱ型）苦参结肠靶向微丸的结肠定位释药性能最佳.