N-［8-(2-羟苯基)氨基］辛酸钠对胰岛素溶液的胃肠道吸收促进作用及机理

目的研究一种合成的吸收促进剂N-［8-(2-羟苯基)氨基］辛酸钠(SNAC)对胰岛素(INS)溶液胃肠道给药的吸收促进作用及作用机制。方法小鼠和大鼠灌胃给药考察SNAC对INS溶液的吸收促进作用;采用大鼠不同肠段给药、能量抑制剂2,4-二硝基苯酚(DNP)和P-糖蛋白抑制剂维拉帕米(Ver)研究SNAC 的促吸收作用机理。结果SNAC可促进INS溶液在消化道的吸收,作用大小与SNAC的量成正比;SNAC的促吸收作用空肠>结肠>回肠,随DNP浓度增大而减小,随Ver浓度增大而增大。结论SNAC对INS的吸收促进作用呈剂量依赖,需要能量,受P-糖蛋白排放影响。

Studies on gastrointestinal absorption enhancement effect and mechanism of sodium N-[8-(2-hydroxybenzyl)amino] caprylate to insulin solution

Aim To study the enhancement effect and mechanism of sodium N -8-(2-hydroxybenzyl)amino] caprylate (SNAC - a kind of synthetic enhancer) to insulin (INS) solution in gastrointestine. Methods To determine the enhancement effect of SNAC on INS absorption by oral administration to rats and mice; To study the enhancement mechanism of SNAC by three kinds of methods: delivering SNAC and INS solution to different parts of rats' intestines, adding energy inhibitor 2,4-dinitrophenol (DNP) or P-glycoprotein (P-gp) inhibitor verapamil (Ver) into SNAC and INS solution. Results SNAC was shown to enhance the gastrointestinal absorption of INS, the intensity of absorption enhancement corresponded to the doses of SNAC. The enhancement of SNAC to INS in different parts of the rat intestine was different (jejunum > colon > ileum). The effect of SNAC on INS absorption increased accordingly. Conclusion The enhancement of SNAC to INS absorption presented dose dependence on SNAC; the absorption process needed energy and related to P-gp efflux.