麝丹眼用即型凝胶的家兔离体角膜渗透特性  

Isolated Corneal Penetration of Muscone and Salvianolic Acid B in Shedan in situ Forming Eye Gels

作　　者：王国华[1] 聂其霞[1] 臧琛[1] 张保献[1] 朱琼[1] 

机构地区：[1]中国中医科学院中药研究所,北京100700

出　　处：《中国实验方剂学杂志》2015年第20期1-4,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家药典委员会2015年版<中国药典>科研课题(1191)

摘　　要：目的:研究麝丹眼用即型凝胶中麝香酮与丹酚酸B经家兔离体角膜的渗透特性,为该制剂的开发提供参考。方法:以含1.0%聚山梨酯-80的生理盐水为释放介质,采用Franz扩散池法考察麝丹凝胶中麝香酮和丹酚酸B经家兔角膜的渗透性;以2,4-二硝基苯肼为衍生剂,衍生温度60℃,衍生时间30 min,对麝丹眼用即型凝胶剂家兔离体角膜渗透的接受液进行衍生,采用高效液相色谱法进行梯度洗脱,同时测定接收液中麝香酮、丹酚酸B的含量;考察不同p H和麝香酮质量分数对麝丹眼用即型凝胶中麝香酮、丹酚酸B离体角膜渗透性的影响,绘制累积释药曲线,建立动力学模型,计算表观渗透系数和稳态流量。结果:麝香酮和丹酚酸B通过角膜的扩散行为均符合零级动力学特征,麝丹凝胶中麝香酮离体角膜渗透特性对p H不敏感,丹酚酸B随p H降低而渗透速率增大;丹酚酸B渗透性随麝香酮质量分数增加而渗透量增加,在麝香酮质量分数为0.5%时,麝香酮表观渗透系数1.530×10-6cm·s-1,稳态渗透速率7.651×10-3μg·s-1·cm-2;在此质量分数下,丹酚酸B的表观渗透系数1.218×10-6cm·s-1,稳态渗透速率6.558×10-3μg·s-1·cm-2。结论:麝香酮可促进麝丹眼用即型凝胶中丹酚酸B的角膜渗透,该凝胶中麝香酮最佳用量0.5%。Objective： To provide a reference for development of Shedan in situ forming eye gels by investigating isolated corneal penetration of muscone and salvianolic acid B in this preparation. Method： Taking physiological saline containing 1% tween-80 as release medium, Franz vertical diffusion cell was adopted to investigate effect of p H and muscone concentration for rabbit cornea permeability of muscone and salvianolic acid B. Release medium was precolumn dedvatized with 2,4-dinitrophenylhydrazine under 60 ℃ for 30 min and was separated by HPLC. Cumulative release curves of muscone and salvianolic acid B were drawn, their kinetics models were established,apparent permeability coefficient and permeation rate of steady state were calculated.Result： Diffusion behavior of muscone and salvianolic acid B through cornea were in line with the zero-order kinetics. In vitro permeation of muscone was not sensitive to p H, while apparent permeability coefficient of salvianolic acid B increased with p H of Shedan gels decreased. Permeability of salvianolic acid B increased with the concentration of muscone increased. When the concentration of muscone reached 0. 5%, apparent permeability coefficient and steady-state flow rate of muscone reached maximum,which were 1. 530 × 10-6cm·s-1and 7. 651 × 10-3μg·s-1·cm-2,respectively; and those for salvianolic acid B were 1. 218 × 10-6cm·s-1and6. 558 × 10-3μg·s-1·cm-2,respectively. Conclusion： Muscone can promote corneal permeability of salvianolic acid B in Shedan in situ forming eye gels,and its optimum dosage is 0. 5%.

关 键 词：麝香酮 丹酚酸B 眼用即型凝胶 离体角膜 表观渗透系数 稳态渗透速率 麝香 

分 类 号：R283.6[医药卫生—中药学] R945[医药卫生—中医学]