胰岛素吸入粉雾剂的体外沉降及大鼠体内吸收促进剂的药效学评价(英文)

Deposition of insulin powders for inhalation in vitro and pharmacodynamic evaluation of absorption promoters in rats

目的采用喷雾干燥法制备胰岛素吸入粉雾剂,对吸入粉雾剂体外沉降性质进行考察,并对其吸收促进剂在大鼠体内的药效学进行初步研究。方法采用中国药典(2000版)附录XH的装置测定粉末的体外有效部位沉积量,以葡糖氧化酶法(GOD-PAP法)测定大鼠的血糖浓度来评价其降血糖效果。结果喷雾干燥法制得的胰岛素吸收粉雾剂沉积量在各湿度下均大于40%,在气流量≥18 L.m in-1的情况下其有效部位沉积量变化不大。8mmol.L-1/dose牛黄胆酸钠[PA=59.91%,Cnad ir=(33±6)%]和10 mmol.L-1/dose去氧胆酸钠[PA=47.46%,Cnad ir=(32±7)%]对胰岛素肺部吸收促进作用明显。而1%辛酸钠、1%十二烷基硫酸钠、250μg/dose卵磷脂和10mmol.L-1/dose EDTA并未显示明显效果。结论制得的胰岛素吸收粉雾剂沉积量受湿度影响小,环境湿度依赖性和吸气流量依赖性小。8 mmol.L-1/dose牛黄胆酸钠和10 mmol.L-1/dose去氧胆酸钠可有效促进胰岛素干粉吸入剂的降血糖效果。

Aim To prepare insulin powder for inhalation by spray-drying technology, determine the deposition of the insulin powder formulation in vitro and preliminarily investigate hypoglycemic response of the dry powder with/without absorption promoters. Methods The depositions of the insulin powder for inhalation were determined by the China Pharmacopoeia 2000 version addenda XH and hypoglycemic effects were evaluated by testing serum glucose with glucose oxidase-peroxidase （GOD-PAP） method.Results The depositions of the spray-dried insulin powder for inhalation were more than 40% under various humidity and their changes were not significant when air flow was no less than 18 L ·min^-1. The coadministration of insulin with 8 mmol·L^-1/dose sodium taurocholate [ PA = 59.91%, Cnadir = （33 ± 6） % ] and 10 mmol·L^-1/dose sodium deoxycholate [ PA = 47.46%, Cnadir = （ 32 ±7 ） % ] induced a significantly greater decline in blood glucose levels, while coadministration with 1% sodium caprylate, 1% sodium dodecyl sulfate, 250μg/dose lecithin, 10 mmol·L^-1/dose EDTA appeared to have no significant effect （P 〉0.05）. Conclusion Insulin powder for inhalation was relatively stable under various humidity conditions and different flow current. The use of 8 mmol·L^-1/dose sodium taurocholate and 10 mmol ·L^-1/dose sodium deoxycholate could be able to potentially improve the bioavailability of insulin by puhnonary route.