摘要
目的:依托国家药品评价抽验项目,采用标准检验与探索性研究相结合的方法对雷公藤多苷片制剂进行质量评价及安全性研究。方法:采用国家药品监督管理局颁标准(WS3-B-3350-98-2011)对10个企业171批次雷公藤多苷片进行标准检验,综合评价产品质量,发现标准存在的问题;同时开展体外毒性实验,初步探讨雷公藤多苷片中潜在肝毒性成分。结果:实验发现,现行标准存在项目设置不合理及设置不足的问题,同时雷公藤多苷片产品质量参差不齐,崩解时间差异大,雷公藤甲素及雷公藤内酯甲含量相差悬殊。此外,体外肝细胞毒性实验显示雷公藤多苷片中单体对琨B及雷公藤红素具有潜在肝毒性风险。结论:雷公藤多苷片质量波动不稳定的主要原因是制剂生产工艺不统一、不固定导致,建议统一该制剂生产工艺;此外针对标准不合理项目建议修订薄层鉴别项下对照品使用浓度,雷公藤甲素检查项增设下限控制,同时增加潜在毒性成分对琨B及雷公藤红素的检查设置。
Objective:Supporting by the National Drug Evaluation and Sampling Project,the quality evaluation and safety study of Leigongteng Duogan Tabelets were performed using a combined method of standard inspection and exploratory research.Methods:A total of 171 batches of Leigongteng Duogan Tabelets from 10 companies were used in the standard inspection followed the standard WS3-B-3350-98-2011 issued by National Medical Products Administration.The qualities of products were comprehensively evaluated to investigate the problems in the existing standard.In the meanwhile,in vitro toxicity study was performed for a preliminary discussion on the potential toxic ingredients in the Leigongteng Duogan Tabelets.Results:It has been found that the testing items listed in the current standard are unreasonable and insufficient.Also,the quality and the disintegration time of Leigongteng Duogan Tabelets varies widely,and the contents of triptolide and wilforlide A differ greatly from products to products.In addition,the in vitro hepatocytes toxicity data showed that the monomers quinone B and tripterine in Leigongteng Duogan Tabelets exhibited hepatotoxicity risks.Conclusion:The unstable quality of Leigongteng Duogan Tabelets is mainly attribute to the inconsistency and instability of the manufacture processes of preparations,thus it is recommended to unify the production process of Leigongteng Duogan Tabelets.In addition,for the unreasonable standard items,it is recommended to revise the concentrations of the reference substances of the thin-layer identification items,add a lower limit control to the triptolide inspection item,and increase the inspection items of quinone B and tripterine as potentially toxic components.
作者
汪祺
王亚丹
郑笑为
文海若
马双成
WANG Qi;WANG Ya-dan;ZHENG Xiao-wei;WEN Hai-ruo;MA Shuang-cheng(National Institutes for Food and Drug Control,Beijing 100050,China)
出处
《中国现代中药》
CAS
2020年第9期1534-1538,共5页
Modern Chinese Medicine
基金
国家自然科学基金项目(81503347)。
关键词
雷公藤多苷片
质量标准
国家抽验
毒性
Leigongteng Duogan tablets
quality standard
national drug sampling and inspection work
toxcity
