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目的 :研究口腔粘膜内酶对胰岛素口腔吸收的影响。方法 :采用三氯醋酸沉淀法 ,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 ,与皮下注射胰岛素比较 ,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 ) ,药理相对生物利用度为 2 89%。喷雾液中加入屈来赛多 (0 1% ) ,药理相对生物利用度为 4 84% ;加入杆菌肽 (0 5 % ) ,药理相对生物利用度为 6 6 0 % ;加入去氧胆酸钠 (1% ) ,药理相对生物利用度为 9 6 0 %。结论 :口腔粘膜中的酶可以限制胰岛素在口腔粘膜的吸收 ,为了提高胰岛素经口腔吸收的生物利用度 ,应该尽量降低口腔粘膜中的酶对胰岛素的降解
Objective: To study the effect of oral mucosal enzymes on insulin oral absorption. Methods: Trichloroacetic acid precipitation method was used to investigate the degradation of insulin under different conditions in hamster oral mucosa homogenate. Enzyme inhibitors (bacitracin and trimetrexate) and sodium deoxycholate were added to the insulin oral spray to examine the blood glucose reduction after oral administration of insulin in rats. Results: Enzyme activity in intestinal mucosal cells was much higher than that in oral mucosal cells. Bacitracin, trimetazidine, and sodium deoxycholate all inhibited the degradation of insulin in the oral mucosa. At the same concentration, sodium deoxycholate has a weaker inhibitory effect than bacitracin, but more potent than bendracoside. Degradation of insulin in the oral cavity of normal hamsters was significantly greater than that of diabetic hamsters. After the addition of bacitracin, trimetazidine and sodium deoxycholate to the insulin solution, the oral administration to normal rats was administered. Compared with the subcutaneous injection of insulin, the pharmacological relative bioavailability increased to some extent. Insulin-only spray solution (insulin blank solution) showed pharmacological relative bioavailability of 2 89%. The relative bioavailability of pharmacokinetics was 4 84%. The addition of bacitracin (0 5%) showed a pharmacological relative bioavailability of 6 6 0%. Sodium deoxycholate (1%), pharmacological relative bioavailability of 96.0%. CONCLUSIONS: Oral mucosal enzymes can limit the absorption of insulin in the oral mucosa. In order to increase the bioavailability of insulin absorbed through the oral cavity, degradation of insulin in the oral mucosa should be minimized