吴茱萸次碱羟丙基-β-环糊精包合物的制备工艺研究  

Preparation process of rutacarpine-hydroxypropyl-β-cyclodextrin inclusion complex

作　　者：严春临[1] 张季[2] 侯勇[2] 薛贵平[2] 王树[2] 赵青亚 

机构地区：[1]河北北方学院基础医学院,河北张家口075000 [2]河北北方学院药学系,河北张家口075000

出　　处：《中国中药杂志》2014年第5期828-832,共5页China Journal of Chinese Materia Medica

基　　金：河北省卫生厅医学科学研究重点课题(20130040);张家口市科技局科技计划指导项目(20100195D)

摘　　要：吴茱萸次碱(rutaecarpine,Rut)是吴茱萸中提取的一种吲哚喹唑啉类生物碱,研究表明吴茱萸次碱有抗高血压、抗癌、抗炎、抗血栓形成等多种药理学作用,目前许多学者正致力于将其开发成一种全新作用机制的抗高血压、抗炎药物,但是研究发现吴茱萸次碱属于既难溶于水又难溶于油的高脂溶性药物,Rut的高度难溶性是其口服吸收应用的主要障碍,极大的降低了吴茱萸次碱的生物利用度,因此本实验以羟丙基-β-环糊精(HP-β-CD)为包合材料制备Rut包合物,以提高吴茱萸次碱的水溶性和生物利用度。该实验采用搅拌法-冷冻干燥法制备Rut-HP-β-CD包合物,以包合率为指标,运用正交试验法,以主客分子摩尔比、包合温度、包合时间、搅拌速度为影响因素,优化Rut-HP-β-CD包合物的制备工艺。通过考察表观溶解度、薄层色谱、显微鉴别和熔点测定、溶出度考察等方法验证包合物。结果显示当Rut与HP-β-CD摩尔比为1∶1,温度60℃、包合时间4 h、搅拌速度600 r·min-1的条件下制备Rut-HP-β-CD包合物,包合率达91.04%,工艺优化成功。因此以最佳工艺条件制备的Rut-HP-β-CD包合物制备工艺简便、易行,包合率高,重复性好,能显著提高Rut的溶解度及生物利用度,为吴茱萸次碱的临床应用提供了可靠实验基础。Rutaecarpine （Rut） is a type of indole quinazoline alkaloid exracted from Ruticarpum. Studies showed that Rut has a wide range of pharmacological effects, such as anti-hypertension, anticancer, anti-inflammation, anti-thrombus formation. Currently, many scholars are committed to developing it into a new antihypertensive and anti-inflammatory drug with all new mechanisms. But studies found that Rut is a highly fat-soluble drug with low water and oil solubility. Its high insolubility is the main obstacle in its oral absorption and application, which greatly reduced its hioavailability. Therefore, hydroxypropyl-fl-cyclodextrin （HP-fl-CD） was used as the inclusion material to prepare Rut-HP-fl-CD inclusion complex in this experiment, in order to increase its water solubility and bioavailability. In this experiment, the inclusion complex was prepared by the stirring-freeze-dry method. The preparation process was optimized by the orthogonal test, with the inclusion rate as the index, and molar ratio between host and guest molecules, inclusion tem- perature, time and stirring speed as the impacting factors. Moreover, the inclusion complex was verified by detecting the apparent solu- bility, thin layer chromatography, microscopic identification, melting point detection and dissolution study. The results showed that un- der the conditions of the molar ratio between Rut and HP-β-CD of 1 ： 1, temperature at 60 ℃, inclusion time of 4h and stirring speed at 600 . min^-1 , the inclusion rate of Rut-HP-fl-CD reached 91.04%. Therefore, the preparation process of Rut-HP-fl-CD inclusion un- der the optimum conditions is simple and feasible, with a highest inclusion rate and reproducibility, and could significantly improve Rut＇s solubility and bioavailability, and provide a reliable experimental basis for its clinical application.

关 键 词：吴茱萸次碱 羟丙基-Β-环糊精 包合物 正交试验 

分 类 号：R284[医药卫生—中药学]