几种吸收促进剂和酶抑制剂对胰岛素结肠吸收的影响

Effects of Absorption Enhancers and Protease Inhibitors on Colonic Delivery of Insulin

以胰岛素为模型药物,分别采用体外、在体和体内的方法进行吸收促进剂或酶抑制剂的筛选。结果表明,体外试验中,同一浓度的不同吸收促进剂或酶抑制剂促进胰岛素结肠黏膜渗透的强弱顺序为:Laureth9>Brij78>SDC>STGC>STC;大鼠在体试验表明,单用胰岛素无降血糖效果,含不同吸收促进剂或酶抑制剂的胰岛素溶液降血糖效果的强弱顺序依次为:Laureth9>SDC>Brij78>STC>STGC>SLC>BTC。正常大鼠灌胃给予含促进剂或抑制剂组合的胰岛素胶囊,其降血糖效果的强弱顺序为:1%Brij78+1%Laureth9>1%SDC+1%Laureth9>1%Brij78+1%SDC。

The enhancing effect of various absorption enhancers or protease inhibitors on permeability of insulin across colonic mucosa of rats was investigated using in vitro, in situ and in vivo method. The results of in vitro experiment showed that the efficacy order of the enhancers or inhibitors at the same concentration in turn was： Laureth9 〉 Brij78 〉 SDC 〉 STGC 〉 STC. In in situ loop method, administration of insulin alone did not decrease the glucose level. Obvious hypoglycemic effects were found when adding absorption enhancers or protease inhibitors, and their efficacy order for enhancing transport of insulin was： Laureth9 〉 SDC 〉 Brij78 〉 STC 〉 STGC 〉 SLC 〉 BTC. In vivo investigation, the decline of blood glucose appeared after delivery of colon-specific capsules. The efficacy of insulin through the colon could be increased by enhancers and inhibitors. The efficacy order of combinatorial enhancers was： 1%Brij78 ＋ 1%Laureth9 〉 1%SDC＋ 1%Laureth9 〉 1%Brij78 ＋ 1%SDC.