地鳖纤溶蛋白口服时间/pH依赖结肠靶向微囊的开发及评价

Development and Evaluation of Time/p H Dependent Oral Colon Targeted Microcapsules of Enpolyp Haga Fibrinolytic Protein

地鳖中的纤溶活性蛋白是从地鳖中提取的具有抗栓及抗肿瘤作用的有效成分,其口服易被上消化道酶分解从而限制了应用。采用恒流泵滴制法开发地鳖纤溶活性蛋白时间/pH依赖口服结肠靶向微囊(EnpolypHaga fibrinolytic protein oral colon targeting microcapsules,CTM-EFP)。采用单因素实验和正交实验相结合的方法寻找到包封率为60.17%±2.72%、载药量为15.50%±0.44%的最佳配方。扫描电子显微镜(SEM)显示微囊呈球形、表面光滑,在人工肠液中24 h的累积释放度为99.53%±0.69%,在人工胃液中24 h累积释放度为7.43±1.04%,通过时间/pH依赖达到结肠靶向作用。CTM-EFP在人工肠液中的体外释放曲线符合Korsmeyer方程,提示地鳖纤溶活性蛋白(EnpolypHaga fibrinolytic protein,EFP)是通过扩散和侵蚀机制结合释放的。CTM-EFP为EFP的口服给药提供了一种新的剂型,为EFP应用于临床提供参考。

EnpolypHaga fibrinolytic protein is the effective components extracted from EupolypHaga sinensis, which has antithrombotic and antitumor effects. Time/pH dependent oral colon targeting microcapsules(EnpolypHaga fibrinolytic protein oral colon targeting microcapsules, CTM-EFP) were developed by constant flow pump infusion method. The best formulation of CTM-EFP was found by single factor test and orthogonal test, which drug loading rate and entrapment efficiency rate was 15.50 ± 0.44%, 60.17 ± 2.72% respectively. Scanning electron microscopy(SEM) showed that the microcapsules were spherical and smooth. The release rate was 99.53 ± 0.69% in the artificial intestinal juice for 24hours, and 7.43 ± 1.04% in the artificial gastric juice for 24 hours, which indicating that CTM-EFP achieve the colon target effect. The in vitro release curve of CTM-EFP in artificial intestinal fluid was in accordance with Korsmeyer et al.’s equation, indicating that EnpolypHaga fibrinolytic protein(EFP) was released through diffusion and erosion mechanism. CTM-EFP is a new dosage form of EFP with p. o administration, and provides a reference for clinical application of EFP.