胰岛素脂质混悬液的肺部给药  

PULMONARY DELIVERY OF INSULIN LIPID SUSPENSION

作　　者：江志强[1] 吕剑[1] 

机构地区：[1]复旦大学药学院药剂学教研室,上海200032

出　　处：《药学学报》2002年第5期378-382,共5页Acta Pharmaceutica Sinica

基　　金：卫生部优秀青年科技人才专项基金 (970 3 3 );上海市卫生局科技发展基金 (0 14 0 9)

摘　　要：目的　研究胰岛素脂质混悬液 (insulinlipidsuspension ,INS LIP SP)经正常大鼠肺部给药后的生物利用度。方法　分别以薄膜 超声分散法和逆相蒸发法制备INS LIP SP ,以sc胰岛素溶液为对照 ,并同气管滴注胰岛素溶液进行比较 ,分别计算气管滴注给药后的药理相对生物利用度 (f% )和药物相对生物利用度 (F % ) ,结合药效学和药动学两方面进行评价。结果　以薄膜 超声分散法和逆相蒸发法制备的INS LIP SP其脂质颗粒平均粒径和跨距分别为1 91μm ,0 94和 2 0 8μm ,1 2 8,包封率分别为 (16 4± 1 6 ) %和 (40± 3) % (n =3) ,肺部给药后f%均达到 37% ,F %均达到 32 % ,与胰岛素溶液肺部给药后的f%和F % (分别为 2 9%和 16 % )比较有显著性差异 (P <0 0 1) ,但不同包封率的INS LIP SP与胰岛素溶液和空白脂质体的物理混合物之间则无显著性差异 (P >0 0 5 )。结论　INS LIP SP肺部给药后可达到较高的生物利用度。AIM To investigate the relative bioavailability of pulmonary delivered insulin lipi d suspension (INS LIP SP) in normal Wistar rats. METHODS INS LIP SP were prepared by two different methods and then delivered to the ra t lung using an intratracheal instillation method. Blood glucose levels and INS concentrations in serum were determined by glucose oxidase method and radioimmun oassay method, respectively. The relative pharmacological bioavailability ( f %) and relative bioavailability ( F %) of INS LIP SP were calculated from th e area above the curve (AAC) and the area under the curve (AUC) compared with su bcutaneous injection of INS solution. RESULTS The mean particle diameter, span of dispersity and entrapment efficiency of INS LIP SP prepared by a membrane formed with sonication method and a reversed p hase evaporation method were 1 91 μm, 0 94 and 16 45% and 2 08 μm, 1 28 a nd 39 51%, respectively. The values of f % and F % of both INS LIP SP w ere up to 37% and 32%, separately, and there was a statistically significant dif ference between INS LIP SP and INS solution. However, there was no significant difference between the two INS LIP SP and the physical mixture of INS solutio n and blank liposomes. CONCLUSION The results showed that INS LIP SP could achieve higher bioavailability fo llowing pulmonary delivery to rats.

关 键 词：胰岛素 脂质混悬液 肺部给药 生物利用度 降血糖作用 

分 类 号：R977.15[医药卫生—药品] R944[医药卫生—药学]