星点设计-响应面法优选马钱子总生物碱微囊制备工艺  

Optimizing preparation technology of strychnos alkaloids microcapsules by central composite design-response surface method

作　　者：宋信莉[1] 杨道斌[1] 王钰乐 张建锋 杜平[1] 卿勇军[1] 刘文[1] SONG Xin-li;YANG Dao-bin;WANG Yu-le;ZHANG Jian-feng;DU Ping;QING Yong-jun;LIU Wen(Guiyang College of Traditional Chinese Medicine, Guiyang 550002, China;Sinopharm Group （Guizhou） Pharmaceutical Co.Ltd, Guiyang 550000, China)

机构地区：[1]贵阳中医学院,贵阳550002 [2]国药集团同济堂(贵州)制药有限公司,贵阳550000

出　　处：《中华中医药杂志》2018年第4期1582-1587,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家苗医药工程技术研究中心(No.2014FU125Q09);贵州省贵阳中医学院院士工作站(No.黔科合院士站[2014]3013号);贵州省卫生计生委科学技术基金项目(No.gzwjkj2014-1-041);贵州省教育厅科技拔尖人才支持项目(No.黔教合KY字[2017]074)~~

摘　　要：目的:优选马钱子总生物碱微囊的制备工艺,对马钱子总生物碱微囊的质量及毒性进行评价初步研究。方法:以壳聚糖、明胶为囊材,采用复乳化-交联法制备马钱子总生物碱微囊,通过星点设计-响应面法优选其制备工艺,并对微囊的载药量、包封率、产率、表征、粒径分布等质量评价指标进行考察。通过急性毒性试验考察马钱子总生物碱微囊的LD50值。结果:马钱子总生物碱微囊最佳工艺处方为壳聚糖质量浓度为1.5%,明胶质量浓度为11%,囊芯囊材质量比为1∶1,戊二醛用量为2m L。载药量为17.84%、包封率为70.31%、产率为91.66%。外观呈圆球形、表面较为光滑、未出现粘连现象,粒径分布较集中,平均粒径为112.47μm。马钱子总生物碱微囊LD50为236.59mg/kg,是马钱子总生物碱的2.23倍。结论:以最佳工艺处方制备马钱子总生物碱微囊工艺合理、稳定,综合质量评价结果表明该微囊质量较好,同时急性毒性试验表明,微囊的LD50较原总生物碱有一定程度的提高,安全性进一步提高,推测可能与缓释过程有关。Objective： To optimize the preparation process of total alkaloids of semen strychni microcapsules, and gelatin as wall materials used to prepare microcapsules containing total alkaloids double emulsion crosquality of microcapsules containing total alkaloids and detoxicating effect evaluation. Methods： Using chitosan aslinking method, through the optimization of the central composite design-respone surface method its preparation process, and to investigate the drug loading, encapsulation efficiency, yield, characterization, particle size distribution and the quality evaluation index of microcapsules. By reducing the toxicity acute toxicity test of total alkaloids of semen strychni microcapsules. Results： The optimum microcapsules containing total alkaloids as the concentration of chitosan was 1.5%, gelatin concentration was 11%, the core capsule material mass ratio was 1 ： 1, the amount of glutaraldehyde was 2mL. The drug loading was 17.84%, encapsulation efficiency was 70.31%, and the yield was about 91.66%. The appearance was round, the surface was smooth, there was no adhesion phenomenon, the particle size distribution was concentrated, the average particle size was 112.471am. The LDs0 of microcapsules of containing total alkaloids was 236.59mg/kg, was 2.23 times the total alkaloid of semen strychni, Conclusion： The optimal prescription preparation containing total alkaloids microcapsules is reasonable, stable and comprehensive quality evaluation results show that the microcapsule quality is good, and the acute toxicity test showed that the microcapsules. The LDs0 of microcapsules increased to some extent compared with the total alkaloids, and the safety is further improved. It may be related to the sustained release process.

关 键 词：马钱子总生物碱 微囊 星点设计-响应面法 急性毒性 制备工艺 

分 类 号：R283.6[医药卫生—中药学]