川芎嗪羟丙基-β-环糊精包合物柔性脂质体的药剂学性质研究  

Study on the pharmaceutical properties of flexible liposome of hydroxypropyl-β-cyclodextrin inclusion complex of ligustrazine

作　　者：付丽娜[1] 李伟泽[1] 赵宁[1] 樊琨 李健 杨黎彬[1] FU Li′na;LI Weize;ZHAO Ning;FAN Kun;LI Jian;YANG Libin(College of Pharmacy,Xi′an Medical University,Xi′an 710021,China)

机构地区：[1]西安医学院药学院,西安710021

出　　处：《西北药学杂志》2021年第4期601-605,共5页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:82004075);陕西高校青年创新团队建设项目(编号:陕教[2019]90号);陕西省中医药管理局科研课题(编号:2019-ZZ-ZY010);陕西省科技厅面上项目(编号:2020JM-610);陕西省教育厅自然科学基金项目(编号:19JK0759)。

摘　　要：目的将川芎嗪(LI)制成羟丙基-β-环糊精(HP-β-CD)包合物(HCD-LI),以包合物为内水相药物制备柔性脂质体(FL),并考察其药剂学性质变化。方法用超声法制备HCD-LI,差示扫描量热仪了解包合效果;用注入法制备川芎嗪柔性脂质体(LIFL)和LI包合物的纳米柔性脂质体(HCD-LIFL);用高效液相色谱(HPLC)法测定LI的含量;用Malvern激光粒度仪测定其粒径与表面电位;以鱼精蛋白沉淀法测定脂质体的包封率;透析法测定脂质体的泄漏率。结果37℃条件下12 h时LIFL的累积泄露率为92%,HCD-LIFL的累积泄露率为58%;HCD-LIFL对LI的包封率为(69.2%±11.4%)(n=3),是LIFL的的1.69倍;LIFL与HCD-LIFL的粒径及电位无显著性差异,其粒径分别为(191.5±3.5)、(240.1±4.2)nm;Zeta电位值分别为(-31.6±2.8)、(-33.9±2.3)mV。结论HCD-LIFL可提高LI的包封率,并能明显降低脂质体内水相药物的泄漏。因此,为进一步研究液体状态下脂质体的稳定性提供了一种新的技术手段和思路。Objective To prepare ligustrazine(LI)hydroxypropyl-β-cyclodextrin(HP-β-CD)inclusion compound(HCD-LI),then prepare the flexible liposome(FL)form inclusion complex as the internal phase drug and to investigate the changes of pharmaceutical properties.Methods The HCD-LI was prepared by using ultrasonic method,and the samples were tested with differential scanning calorimetry(DSC).Ligustrazine flexible liposome(LIFL)and HCD-LI flexible liposome(HCD-LIFL)were prepared by using injection method.The content of LI was determined by HPLC.The size and surface potential of particle were measured by Malvern laser particle size analyzer.The encapsulation rate of liposomes was determined by protamine precipitation method and the leakage rate of liposome was determined by dialysis.Results At 12 hours,the cumulative leakage rate of LIFL was 92%,while the cumulative leakage rate of HCD-LIFL was only 58%at 37℃.The encapsulation rate of ligustrazine for HCD-LIFL was(69.2%±11.4%)(n=3),which was 1.69 times higher than LIFL.There was no significant difference between LIFL and HCD-LIFL in terms of particle size and potential.The particle sizes were(191.5±3.5)nm and(240.1±4.2)nm,and the Zeta potentials were(-31.6±2.8)mV and(-33.9±2.3)mV,respectively.Conclusion HCD-LIFL can improve the encapsulation rate of LI,and significantly reduce the leakage of aqueous phase drugs in liposomes.Therefore,this study provides a new technical means and ideas for further study on the stability of liposomes in liquid state.

关 键 词：川芎嗪(LI) 柔性脂质体(FL) 羟丙基-β-环糊精(HP-β-CD) 包合物 

分 类 号：R94[医药卫生—药剂学]