正交试验优化硫酸长春新碱脂质体的制备工艺  

Optimization of preparation technology of Vincristine Sulfate Liposomes by orthogonal test

作　　者：吴溪[1,2] 李文静[1] 杨志强[2] 王杏林[2] 张雪冰[1,2] 

机构地区：[1]天津中医药大学,天津300193 [2]天津药物研究院,天津300193

出　　处：《现代药物与临床》2015年第6期653-657,共5页Drugs & Clinic

基　　金：国家重大新药创制项目(2014ZX09507005-001)

摘　　要：目的制备性质稳定的硫酸长春新碱脂质体。方法采用单因素试验考察磷脂与胆固醇比例、药脂比、脂质浓度、载药温度、载药时间、外水相p H值对硫酸长春新碱脂质体包封率的影响。以包封率为指标,分别以氢化磷脂(SPC-3)和二硬脂酰磷脂酰胆碱(DSPC)为磷脂材料,通过正交试验考察载药温度、药脂比和载药时间对制备工艺的影响,优化出硫酸长春新碱脂质体的最佳制备工艺。结果硫酸长春新碱脂质体的最佳制备工艺为:将药物溶液(按照药物含量计)和空白脂质体溶液(按照脂质含量计)按照1∶20的比例混合,用Na2HPO4直接调节外水相p H值至7.2。SPC-3脂质体在65℃条件下载药,载药时间30 min。DSPC脂质体在60℃条件下载药,载药时间10 min。结论优选出的硫酸长春新碱脂质体的处方工艺稳定可行。Objective To prepare stable Vincristine Sulfate Liposomes.Methods Single factor tests were used to investigate the effects of formulation and process factors, such as phospholipids and cholesterol radio, drug fat ratio, fat concentration, drug loading temperature, drug loading time, and pH value of water external phase on the encapsulation efficiency of Vincristine Sulfate Liposomes. Then, the optimal preparation technology of Vincristine Sulfate Liposomes with SPC-3 and DSPC as phospholipid material was optimized by orthogonal test to investigate influence of drug loading temperature, drug fat ratio, and drug loading time to the preparation technology, taking encapsulation efficiency as index.Results The best formulation and process of Vincristine Sulfate Liposomes was as following： vincristine sulfate solution and blank liposome solution was mixed by the ratio of 1：20, and then Na2HPO4 was used to regulate the pH value of liposome external phase to 7.2. SPC-3 liposomes uptook drugs at 65℃, and the drug loading time was 30 min. DSPC liposomes uptook drugs at 60℃, and the drug loading time was 10 min.Conclusion The optimized preparation technology of Vincristine Sulfate Liposomes is stable and feasible.

关 键 词：硫酸长春新碱脂质体 硫酸长春新碱 制备 正交试验 

分 类 号：R944[医药卫生—药剂学]