口腔粘膜内酶对胰岛素口腔吸收的影响

目的　研究口腔粘膜内酶对胰岛素口腔吸收的影响。方法　用三氯醋酸沉淀法,考察胰岛素在仓鼠口腔粘膜匀浆物中不同条件下的降解情况。在胰岛素口腔喷雾剂中加入酶抑制剂(杆菌肽、屈来赛多)和去氧胆酸钠,考察了大鼠经口腔喷入胰岛素后的血糖降低情况。结果　小肠粘膜细胞内酶活性远高于口腔粘膜细胞中的酶的活性。杆菌肽、屈来赛多和去氧胆酸钠均能抑制口腔粘膜内胰岛素的降解。在相同浓度下,去氧胆酸钠的酶抑制作用比杆菌肽弱,但比屈来赛多强。胰岛素在正常仓鼠口腔内的降解显著大于糖尿病仓鼠。胰岛素溶液中加入杆菌肽、屈来赛多及去氧胆酸钠后,给正常大鼠口腔喷雾给药,药理相对生物利用度分别有不同程度的提高。只含胰岛素的喷雾液(胰岛素空白液) ,喷雾液中加入屈来赛多(0.1% ) ,加入杆菌肽(0.5% ) ,去氧胆酸钠(1% ) ,与sc胰岛素比较药理相对生物利用度分别为2.89% ,4.84% ,7.52 %和9.60%。结论　口腔粘膜中的酶可以限制胰岛素在口腔粘膜的吸收

EFFECT OF ENZYMES IN BUCCAL MUCOSA ON INSULIN BUCCAL ABSORPTION

AIM To evaluate the effect of proteolytic enzymes on the absorption of insulin in the buccal mucosa. METHODS The trichloroacetic acid method was used to estimate the degradation of insulin under different conditions in the buccal mucosal homogenates. In vivo experiments estimating the enhancement of hypoglycaemic effect by enzyme inhibitors were also conducted. RESULTS Proteolytic enzymes in the buccal mucosa were less active than in the intestine. Bacitracin, aprotinin and sodium deoxycholate can inhibit the degradation of insulin in the buccal mucosal homogenates. The degradation of insulin in buccal mucosal homogenates of normal hamster was smaller than that of diabetic hamster. In vivo experiments of hypoglycaemia supported the in vitro experiments. When given buccally, bacitracin, aprotinin and sodium deoxycholate could increase the relative pharmacological bioavailability of insulin. When co administered with aprotinin (0 1%), bacitracin (0 5%) and sodium deoxycholate (1%), the relative pharmacological bioavailabilities of insulin were 4 84%, 7 52% and 9 60%, respectively. CONCLUSION The in vitro and in vivo results suggest that proteolytic enzymes limit absorption of insulin in the buccal. The enzyme activity should be minimized in order to improve the bioavailability of insulin via buccal delivery.