吸收促进剂对蚓激酶肠道吸收的影响

Effects of absorption enhancers on intestinal absorption of lumbrokinase

目的研究蚓激酶(YJM-I)和吸收促进剂合用时在大鼠肠道各段的吸收特点,寻找YJM-I经肠道吸收的最佳位置和考察吸收促进剂对YJM-I在肠道吸收过程中的影响。方法采用体外扩散池法、十二指肠部位直接给药、在体循环灌流及肠段原位结扎等方法对荧光标记的FITC-YJM-I在大鼠肠道的吸收情况进行了研究。结果十二指肠部位给药后的药代动力学和药效学评价结果显示YJM-I药物分子可被大鼠肠道吸收进入血液循环并保持生物学活性,但其绝对生物利用度较低。体外肠黏膜通透性试验及体内肠段吸收试验结果显示部分吸收促进剂表现出良好的促进YJM-I肠道吸收的作用。十二指肠、空肠和回肠段体外肠黏膜通透性均显示了相似的吸收促进剂作用强弱趋势:1%壳聚糖>1%去氧胆酸钠>1%Na2EDTA>1%十二烷基硫酸钠>1%辛酸钠>1%泊洛沙姆>1%羟丙基-β-环糊精。而在体内十二指肠部位给药则显示的强弱顺序为:2.5%去氧胆酸钠>2.5%Na2EDTA>2.0%壳聚糖>2.5%十二烷基硫酸钠>2.5%辛酸钠>2.5%泊洛沙姆>2.5%羟丙基-β-环糊精。结论吸收促进剂能有效地增加YJM-I肠道吸收程度,其中具有生物黏附作用的壳聚糖有望成为YJM-I肠道吸收的良好促进剂。

Aim To explore the intestinal absorption characteristics of lumbrokinase （YJM-I） in the absence or presence of various absorption enhancers and to find the optimum intestinal site for YJM-I absorption. Methods The absorption kinetics and absorption intestinal sites for YJM-I absorption were investigated with the method of diffusion cell in vitro, duodenum bolus injection, recirculating perfusion and in situ duodenum perfusion in vivo. Results YJM-I could be transported into blood and kept its biological activity across intestinal endothelial membrane after administration via duodenum site, whereas with lower bioavailability. Some of the absorption enhancers were shown good enhancement effects on intestinal absorption of YJM-I in vitro and in situ experiments. The order of enhanced efficiencies of various enhancers on duodenum, ileum and jejunum in vitro permeation experiments were shown as follows： 1% chitosan 〉 1% SDCh 〉 1% Na2EDTA 〉 1% SDS 〉 1% sodium caprylate 〉 1% poloxamer 〉 1% HP-β-CD. The order of enhanced efficiencies of various enhancers on duodenum absorption of YJM-I in vivo were as follows： 2.5% SDCh 〉 2.5% Na2EDTA 〉 2.0% chitosan 〉 2.5% SDS 〉 2.5% sodium caprylate 〉 2. 5% Poloxamer 〉 2.5% HP-β-CD. Conclusion The results indicated that the absorption of YJM-I could be enhanced by various enhancers, and duodenum was the optimum absorption site of YJM-I. Furthermore, bio-adhesive chitosan might be a potential enhancer of intestinal YJM-I absorption.