【摘要】 目的：研究胰岛素溶液（ＩＮＳＳＯＬ）经正常大鼠肺部给药后的降血糖作用。方法：以血糖水平为指标，考察各种吸收促进剂以及酶抑制剂经正常大鼠肺部给药后对ＩＮＳＳＯＬ降血糖作用的影响。同时比较了ＩＮＳＳＯＬ在两种ｐＨ条件下的降血糖作用，并以皮下注射为对照，计算不同条件下ＩＮＳＳＯＬ的药理生物利用度（ｐｈａｒｍａｃｏｌｏｇｉｃａｌｂｉｏａｖａｉｌａｂｉｌｉｔｙ，ＰＢＡ）。结果：０５ｕ·ｋｇ－１的ＩＮＳＳＯＬ经肺部给药后即有明显的降血糖作用，在不加吸收促进剂的条件下的ＰＡ为２６０％。辛酸钠、胆酸钠、苄泽３５、苄泽７８和酶抑制剂杆菌肽均显著地增加ＩＮＳＳＯＬ的降血糖作用。ＩＮＳＳＯＬ在ｐＨ３时的降血糖效果比ｐＨ７时有显著的提高。结论：ＩＮＳＳＯＬ经肺部给药后有显著的降血糖效果。更多还原

【Abstract】 AIM: To investigate the hypoglycaemic effect of pulmonary delivered insulin solution (INS SOL) on normal rats. METHODS: INS SOL was administered to the exposed trachea of anesthetized normal rats. Blood samples were collected at specified intervals and blood glucose levels were determined by glucose oxidase method. The hypoglycaemic response was examined after intrapulmonary delivery of INS SOL in three doses (0 5, 1 0 and 5 0 u·kg -1 ) and under two pH conditions (pH 3 and pH 7), as well as co administration of protease inhibitor (bacitracin) or absorption enhancers. The pharmacological bioavailability (PBA), calculated from area above the curve (AAC) was used to evaluate the absorption enhancement of INS SOL from the lung under various conditions. RESULTS: In the absence of additives, a low dose of insulin solution (0 5 u·kg -1 ) produced significant hypoglycaemic effect following intrapulmonary administration, which showed a PBA of 26 0%. The concomitant administration of sodium caprilate, sodium cholate, Brij35, Brij78 as well as bacitracin appeared to be more effective for enhancing the pulmonary absorption of insulin than the other adjuvants like oleic acid, EDTA and 2 hydroxypropyl β cyclodextrin. Absorption of INS SOL under pH 3 condition was significantly increased compared with that under pH 7 condition. CONCLUSION: Pulmonary delivery of INS SOL produced significant hypoglycaemic effect on normal rats, the pulmonary route may be useful for the delivery of insulin.更多还原