羟丙基-β-环糊精/胰岛素的合适包合比及体外透膜能力研究

目的]研究羟丙基-β-环糊精/胰岛素包合的合适比例及经包合后的胰岛素的体外透膜能力。方法]连续递变试验测定包合比递增的作用变化,溶液法制备包合物;DTA和1H-NMR验证包合物;HPLC检测中性条件下包合后胰岛素的溶解度;Caco-2细胞模型考察包合后胰岛素的体外透膜能力。结果]羟丙基-β-环糊精与胰岛素分子比增大至120∶1,包合作用仍未现饱和;40∶1分子比包合物中胰岛素中性条件溶解度达16.70 g/L,且胰岛素表观渗透系数较包合前增大约10倍。结论]羟丙基-β-环糊精包合胰岛素难达饱和,其40∶1包合物即有较高胰岛素Caco-2细胞转运能力。

Research of Appropriate Inclusion Ratio of Inclusion/HP-O-CD Complex and It's Transcellular Permeation in vitro

Objective] The appropriate inclusion ratio between HP-β-CD and insulin and the ability of the transcellular permeation of insulin after inclusion in vitro was studied.Method] The variations of UV absorption was determined by increase the inclusion ratio by degrees and the inclusion complexes was prepared by solution method,characterized by the DTA method,nuclear magnetic resonance method(1H-NMR).The neutral solubility of insulin was measured by HPLC.Caco-2 cell line was used to examine the transcellular permeation of insulin in vitro model.Result] The inclusion effect hadn't been saturation when the inclusion ratio was raised up to 120∶ 1.The inclusion complex of 40∶ 1 increased the solubility of insulin in the neutral solution up to 16.70 g/L,and increased the apparent permeability about ten times.Conclusion] It was difficult to reach the saturation of the effect between INS /HP-β-CD complex,and the inclusion complex of 40∶ 1 could evidently increase transcellular passage of insulin in Caco-2 cell.