胰岛素油相制剂给药方法和作用机制的研究

 目的通过比较胰岛素油相制剂口服给药和肠道给药的降血糖作用,以及胰岛素油相制剂经小肠灌流后肝门静脉和肝静脉的血胰岛素水平,研究胰岛素油相制剂的合适给药方法与作用机制。方法采用专利方法制备胰岛素油相制剂。糖尿病大鼠分别口服和十二指肠注入胰岛素油相制剂后测定血糖,正常大鼠小肠灌流胰岛素油相制剂后用RIA方法测定肝门静脉和肝静脉血液中胰岛素。结果糖尿病大鼠实验显示,当肠道用药量是口服用药量的1/3时,肠道给药比口服给药降血糖AUC_0-6h提高67%,两者相比有显著性差异(P<0.05)。小肠灌流实验显示,肝门静脉胰岛素浓度显著高于肝静脉胰岛素浓度(P<0.05),胰岛素油相制剂透过小肠上皮细胞的能力显著高于胰岛素水溶液(P<0.05)。同时血糖浓度与肝门静脉和肝静脉中的胰岛素浓度差值显示了很好的负相关关系。结论该油相制剂能有效保护胰岛素的活性。肠道给药比口服给药用药剂量低,降血糖效果好。小肠灌流实验表明,油相制剂中的胰岛素经过肝脏时主要因首过效应而发挥生物学作用。该油相制剂的合适剂型为肠溶胶丸。

Studies on Administration and Mechanism of Insulin Oily Formulation

OBJECTIVE To study the proper administration and mechanism of insulin oily formulation,by comparing the hypoglycemic effects after oral and intestinal administration with insulin oily formulation,and the blood insulin concentrations of hepatic portal vein and hepatic vein after intestinal perfusion with insulin oily formulation.METHODS The insulin oily formulation was prepared with the method of the patent.The blood glucose concentrations of diabetic rats were tested after oral administration and intestinal injection with insulin oily formulation,and the blood insulin concentrations of normal rats were tested by RIA after intestinal perfusion with insulin oily formulation.RESULTS In the diabetic rats experiment,the ratio of relative biological effectiveness after intestinal injection to that after oral administration is 5.00,and there was significant difference between the two groups(P<0.05).In the intestinal perfusion experiment,the blood insulin concentration in hepatic portal vein was significant higher than that in hepatic vein(P<0.05),and the ability of insulin oily formulation to permeate intestinal epithelia was significantly stronger than that of insulin water solution(P<0.05).Moreover the concentration of blood glucose was negatively correlative to the difference of the blood insulin concentrations between hepatic portal vein and hepatic vein.CONCLUSION This oily formulation could protect the activity of insulin intestinally rather than direct orally administrated.The insulin in the oily formulation was eliminated by the first pass effect of the hepatic after its pharmacological effect was exerted.Enteric-coated soft capsules may be a suitable preparation for it.