复方车前凝胶贴膏的制备及初步评价

Preparation and preliminary evaluation of compound plantaginis semen gel paste

关键词:  Plackett-Burman  Box-Behnken  凝胶贴膏  体外释放  H22肝癌腹水模型

Key words:  Plackett-Burman  Box-Behnken  Gel Paste  in vitro release  H22 hepatoma ascites model

摘要:

[目的]研究旨在将复方车前水浸膏制备为易于使用的复方车前凝胶贴膏。[方法]采用Plackett-Burman设计联合Box-Behnken响应面优化法，以初黏力、持黏力、180°剥离强度为评价指标，优选最佳制备处方。采用改良Franz扩散池法，以京尼平苷酸为指标，研究其体外释放行为。以小鼠H22肝癌腹水模型对其药效进行评价。[结果]优化得到复方车前凝胶贴膏的基质配方为NP700，PVPK90，甘油，甘羟铝，酒石酸，蒸馏水（8：5.38：32.5：0.5：0.5：44.62）。凝胶膏中京尼平苷酸24 h体外释放（81.23±1.52）%。给药7 d后，与模型组相比，贴膏组与浸膏组小鼠腹水量显著减少（P<0.01），腹水中VEGF的量显著下降（P<0.05），免疫功能破坏得到显著改善（P<0.05），且贴膏组与浸膏组差异无统计学意义。[结论]复方车前凝胶膏的处方合理，制备的凝胶膏黏性良好，指标成分京尼平苷酸体外释放率符合一级动力学方程，复方车前凝胶贴膏能有效减少小鼠腹水量，效果显著。

Abstract:

[Objective] The aim of this study is to prepare compound Plantaginis semen Extractum(CPE) as an easy-to-use Compound Plantaginis semen Gel Paste(CPGP).[Methods] Plackett-Burman design combined with Box-Behnken esponse surface methodology was used to optimize the preparation formulation with initial bonding strength, holding force, peel strength of 180° as the evaluation index. Modified Franz diffusion cell was used to study in vitro release behavior of CPGP. A preliminary evaluation of the efficacy of CPE and CPGP on the H22 hepatoma ascites model in mice was carried out.[Results] The optimized matrix formulation of CPGP is NP700, PVPK90, glycerol, aluminium glycinate, tartaric acid, distilled water (8:5.38:32.5:0.5:0.5:44.62). The in vitro release rate of geniposide in the CPGP was (81.23±1.52)% at 24 h. The results showed that the CPGP formulation was reasonable. The viscosity of gel paste prepared by the formulation was suitable. In animal experiment, compared with the model group, the volume of ascites mice grouped in CPGP and CPE was very significantly decreased (P<0.01) and the VEGF content in ascites was significantly decreased (P<0.05), also the destruction of immune function was significantly improved (P<0.05) after the treatment for 7 days. Meanwhile the gel paste group and extract group showed no significant difference.[Conclusion] Therefore, the research showed a reasonable CPGP prescription. The release rate of the target component geniposide was in accord with the first order kinetic equation. CPGP effectively reduced the amount of ascites in mice.