【作者】 雷伯开； 金方；

【Author】 Lei bokai,Jin fang(Shanghai Institute of Pharmaceutical Industry, Shanghai 200437)

【机构】 上海医药工业研究院；

【摘要】 目的:研究以卵磷脂微乳为载体和以壳聚糖为粘附剂和吸收促进剂对胰岛素经鼻给药的渗透扩散作用。方法:制备了含0.4%壳聚糖、以磷脂微乳为载体的胰岛素鼻腔喷雾剂,考察了空白微乳在不同PH和不同含量的壳聚糖条件下的粒径、zeta电位。采用离体牛鼻粘膜固定在Franz扩散池,比较胰岛素溶液、含壳聚糖溶液、微乳以及喷雾剂在进行壳聚糖粘膜的体外渗透扩散试验。采用健康家兔鼻腔喷雾给药进行胰岛素降血糖研究。结果:在PH4.0以上时微乳带负电荷,且随PH升高而增加;壳聚糖的加入对微乳电荷产生逆转效应,粒径增加。体外透膜实验中,粘膜经壳聚糖预处理后胰岛素喷雾剂的Papp为16.07±3.83(×108cm/s)而未经壳聚糖预处理时的胰岛素溶液的Papp仅为0.92±0.13(×108cm/s)。家兔药效学实验中,经壳聚糖预处理下,胰岛素喷雾剂最大降糖率为53.92%;未经壳聚糖预处理下胰岛素喷雾剂最大降糖率为39.71%、含壳聚糖溶液为31.42%。结论:以卵磷脂微乳为载体和壳聚糖为吸收促进剂均可显著增加胰岛素的粘膜渗透能力和提高胰岛素的降血糖作用。更多还原

【Abstract】 OBJECTIVE To study the lipid microemulsion as a carrier and chotosan as absorption enhancer in promoting the absorption of intranasal delivery of insulin. METHODS Isulin microemulsion was prepared .The in vitro transportation of insulin across cattle nose nasal membranes was studied used the Franz diffusion cell. The permeation capacity of insulin spray、insulin microemulsion、insulin-chitosan solution and insulin solution were compared with the nasal membranes that were pretreated using the chitosan solution or without .The hypoglycemic activity of above insulin preparation was studied . RESULTS The in vitro transportation of insulin across cattle nasal membranes illustrate that the insulin spray show a highest Papp of (16.07±3.83) ×108 cm/s.The maximum serum glucose decrease of ins-spray is 53.92%. CONCLUSION The lipid microemulsion as a carrier and chotosan as an absorption enhancer can obviously promot the transportation of intranasal delivery of insulin and have significant effect of hypoglycemic activity.更多还原