胰岛素无水反胶束油溶液的体外性质及对正常大鼠的降血糖作用考察

In vitro characteristics and hypoglycemic effects of insulin anhydrous reversed micelles

目的为进一步的制剂研究奠定基础。方法观察油溶液遇水乳化后的形态、粒径分布,采用HPLC法测定不同稀释倍数和不同pH值下油溶液的释放度,采用单因素方差分析法比较大鼠给药组(40U·kg-1)与空白组间各时间点血糖水平的差异,计算相对药理生物利用度。结果油溶液乳化后平均粒径为(2.45±1.43)μm;稀释倍数升高会略增加胰岛素的释放,在pH2.0的稀释介质中胰岛素释放得最多;灌胃组血糖没有显著性变化(P】0.05);十二指肠给药组的相对生物利用度为4.41%。结论胰岛素油溶液在胃肠道中能够自乳化,灌胃给药组没有显著的降血糖作用,十二指肠给药组降糖效果显著,胰岛素在肠道的吸收较胃部的吸收好。

Objectives To investigate the in vitro characteristics of insulin anhydrous reversed micelles (ARMs) and its in vivo hypoglycemic effects in normal rats. Methods The size distribution of the emulsion after insulin anhydrous reversed micelles being emulsified was studied and its release behavior in different dilution volumes and pH media was investigated. The difference of blood glucose level among rendered groups and blank group at each time point was examined using one-way analysis of variance and the relative pharmacological bioavailability was calculated. Results The mean diameter of ARMs was (2.45±1.43) μm. The maximum release of insulin appeared in acidic medium and the dilution volume slightly affected the release. In contrast to intro stomach, the intro duodenum group had significant hypoglycemic effect with relative bioavailability of 4.41 %. Conclusions The insulin anhydrous reversed micelles can be self-emulsified in gastrointestinal tracts and can be absorbed efficiently in intestinal tract to produce significant reduction of blood glucose.