三七叶总皂苷脂质体凝胶剂的制备及其离体透皮率考察

Preparation and in vitro Transdermal Absorption of Total Saponins from Leaves of Notoginseng Radix et Rhizoma Liposomal Gels

目的：优选三七叶总皂苷脂质体凝胶剂的处方工艺并考察其离体累积透皮吸收率。方法：采用薄膜分散法制备脂质体，以包封率为指标，通过正交试验考察选择磷脂与胆固醇的质量比、脂类与药物的质量比、药物质量浓度对三七叶总皂苷脂质体处方工艺的影响。运用高速离心法测定包封率，以卡波姆940为基质制备凝胶剂，通过单因素试验筛选卡波姆940用量。通过体外透皮试验考察三七叶总皂苷中人参皂苷Rb；的体外透皮吸收情况，利用HPLC测定透过及滞留在皮肤内的人参皂苷Rb，含量，色谱条件为ZORBOXSB—C18色谱柱（4．6rnm×250mm，5μm），流动相乙腈（A）-0．2％磷酸（B）梯度洗脱（0～19min，30％A；19～21rain，35％A；21～26min，50％A），检测波长203nm。结果：优选的处方工艺为卵磷脂一胆固醇（4：1），人参皂苷Rb，质量浓度90g·L^-1，脂药比（6：1），当卡波姆940质量分数为0．5％时，药物的皮肤累积透过量最大。结论：脂质体凝胶能提高药物中有效成分在皮肤的透过量，为三七叶总皂苷新剂型和新给药途径的开发提供参考。

Objective： To optimize prescription of total saponins from leaves of Notoginseng Radix etRhizoma liposomal gels and investigate its in vitro transdermal absorption properties. Method： Total saponins from leaves of Notoginseng Radix et Rhizoma liposomes were prepared by thin-film dispersion Method, with encapsulation efficiency as index, orthogonal test was adopted to optimize liposomes formulation by taking ratio of phospholipids-cholesterol, lipids-drug ratio and drug concentration as factors. High-speed centrifugation method was used to determine encapsulation efficiency, carbomer 940 was added as a substrate for preparation of gels, its dosage was investigated by single factor test. In vitro transdermal test was adopted to investigate in vitro transdermal absorption of ginsenoside Rb3 from total saponins in leaves of Notoginseng Radix et Rhizoma, the content of ginsenoside Rb3 was determined by HPLC, chromatographic conditions were as follows： ZORBOX SB-CI8 column （4.6 mm× 250 mm, 5 μm）, mobile phase of acetonitrile （A） -0.2% phosphoric acid （B） gradient elution （0-19 min, 30% A; 19-21 min, 35% A; 21-26 min, 50% A）, detection wavelength 203 nm. Result： Optimized formulation technology was： lecithin-cholesterol （4： 1）, the concentration of ginsenoside Rb3 90 g ·L^-1, lipid-drugs （6：1 ） , the highest cumulative permeation rate of drug through skin when the content of carbomer 940 was 0.5%. Conclusion： Liposomal gels could increase permeation amount of active ingredients in skin, this study laid experimental foundation for development of new dosage forms and new administration routes.