口服胰岛素微球促吸收剂的体外筛选

Study on absorption enhancers for orally administered insulin microspheres in vitro

目的 :筛选用于口服胰岛素的促吸收剂 .方法 :以胰蛋白酶为模型药物 ,通过体外肠囊翻转实验 ,以肠囊内外液中酶活力的比值为评价指标 ,考察胆盐、脱氧胆酸钠、十二烷基硫酸钠、氮酮、脑磷脂、EDTA及其复方的促吸收效果 .结果 :单独使用时 ,胆盐Ⅲ号 (BSⅢ )的促吸收效率最低 ,3h仅为 11.8% ,脱氧胆酸钠的促吸收率最高 ,3h为 5 9.7% ;复合促吸收剂脱氧胆酸钠 +氮酮 +脑磷脂能在 3h内达到最佳促吸收效果 ,吸收率为 81.3% .结论 :复合促吸收剂的效果优于单一促吸收剂 ,脱氧胆酸钠 +氮酮 +脑磷脂的促吸收效果最好 .

AIM: To select the effective absorption enhancers applied to the orally administered insulin microspheres. METHODS: Reverted sac experiments were employed in vitro to select these absorption enhancers including deoxycholate sodium, azone, sodium dodecyl sulphate (SDS), ethylenediaminetetraacetic acid (EDTA) and cephalin. In the experiment, the trypsin was used as a model drug and the ratio of trypsins activity in the outer and inner sac was used as the index to evaluate the efficiency. RESULTS: Three hours after the single administration of each absorption enhancer, the absorption rate of trypsin with the aid of the bile salt Ⅲ was the lowest (only 11.8%) and the deoxycholate sodium was the highest (59.7%). The compound administration of absorption enhancers, deoxycholate sodium plus azone plus cephalin had the absorption rate of 81.3%. CONCLUSION: Compound absorption enhancers are better than the single ones. The combination of deoxycholate sodium plus azone plus cephalin has the best result and can thus be used to the further animal experiment in vivo .