马钱子总碱脂质液晶纳米粒的制备和体外评价研究  

Study on preparation and evaluation in vitro of TASS-LLCN

作　　者：金晨 陈家乐 徐玲霞 管咏梅 刘丽丽 朱卫丰 吴璐 张凌 陈丽华 JIN Chen;CHEN Jia-le;XU Ling-xia;GUAN Yong-mei;LIU Li-li;ZHU Wei-feng;WU Lu;ZHANG Ling;CHEN Li-hua(Key Laboratory of Modem Preparation of Traditional Chinese Medicine (TCM),Ministry of Education,Jiangxi University of TCM,Nanehang 330004,China)

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004

出　　处：《中草药》2018年第22期5305-5312,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81460606);江西省卫生计生委中医药科研计划(2014A059)

摘　　要：目的制备一种马钱子总碱(TASS)的新剂型,以期提高TASS的载药量和经皮渗透性能。方法采用热溶剂-高压均质法制备马钱子总碱脂质液晶纳米粒(TASS-LLCN),采用超滤离心法测定包封率,以包封率为指标采用星点设计-响应面法优化TASS-LLCN的处方,并对优化后制备的TASS-LLCN的基本性能进行评价。同时,采用Franz扩散池法比较TASS-LLCN凝胶和TASS普通凝胶的体外经皮渗透特性,初步考察TASS-LLCN凝胶的经皮渗透行为。结果 TASS-LLCN的最佳制备处方为甘油单油酸酯(GMO)1 403.19 mg、GMO-泊洛沙姆407(GMO-F127)质量比为7.25∶1、载药量为9.48%,预测包封率为64.01%;制剂质量评价显示制得的纳米粒平均粒径为186 nm左右,Zeta电位为-33.1 mV,pH值6.83,稳定性良好;透皮实验显示,TASS-LLCN的24 h累积透过量和渗透速率均大于TASS普通凝胶,具有显著性差异(P<0.05),可以促进有效成分的吸收;TASS-LLCN的皮肤滞留量大于TASS普通凝胶,说明药物在皮下形成储库,有利于药物的持续释放。结论 TASS-LLCN可显著提高TASS的载药量和经皮渗透性能,是一种潜在的具有缓释作用的新型药物。Objective To prepare a new kind of preparation formulation of the total alkaloids from seed of Strychni Semen(TASS), by which could improve their drug loading content and the transdermal function. Methods TASS-LLCN were prepared by hot solvent and high pressure homogeneous method. Using encapsulation efficiency(EE) measured by ultrafiltration as index, the prescription of TASS-LLCN was optimized by response surface methodology with central composite design, and the basic properties of the optimized TASS-LLCN was evaluated. The Franz diffuser method was used to compare the transdermal capacity of both LLCN gel and ordinary gel of TASS. Results The best prescription of TASS-LLCN was as follow: the content of glycerin monooleate(GMO) was 1 403.19 mg/m L, the ratio between GMO and F127 was 7.25∶1, the drug loading content was 9.48% and the predicted encapsulation efficiency was 64.01%. The evaluation of basic properties of the optimized TASS-LLCN showed that the average grain diameter was about 186 nm, zeta potential was-33.1 mV, pH was 6.83, the stability was good. The transdermal experiment in vitro showed that the cumulate osmotic quantities in 24 h and the permeation rate of TASS-LLCN gel were both better than ordinary gel of TASS, which had obvious discrepancy(P < 0.05) and showed that LLCN could promote the absorption of active components; the skin retention volume of LLCN gel was still bigger than ordinary gel, which showed that LLCN gel of TASS could store in the skin and release the drug sustainedly. Conclusion TASS-LLCN could obviously enhance the drug loading content and the transdermal function. It is a potential new kind of preparation formulation which have the sustainable effect.

关 键 词：脂质液晶纳米粒 马钱子总碱 包封率 星点设计一响应面法 Franz扩散池法 马钱子碱 士的宁 

分 类 号：R283.6[医药卫生—中药学]