中国中药杂志

2019, v.44(20) 4329-4335

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QbD理念的经典名方研究:四物汤加减方的提取工艺优化研究
Research of classical prescription based on QbD concept:optimization of extraction process for modified Siwu Decoction

黄兴国;张静;杜文慧;江宗岳;杨继;吴志生;
HUANG Xing-guo;ZHANG Jing;DU Wen-hui;JIANG Zong-yue;YANG Ji;WU Zhi-sheng;School of Chinese Materia Medica,Beijing University of Chinese Medicine;Beijing Qihuang Foundation for Scientific Development of Traditional Chinese Medicine;

摘要(Abstract):

质量源于设计(quality by design,QbD)作为一种先进的国际制剂研究理念,能够完成药品质量从检验出来到设计出来的策略要求。该文基于质量源于设计(QbD)理念,优化经典名方四物汤加减方——养宫方的提取工艺。以固体物质提取量、阿魏酸含量以及芍药苷含量为关键质量属性(critical quality attributes,CQAs),采用失效模式及效应分析(failure mode and effects analysis,FMEA)筛选潜在关键工艺参数(potential critical process parameters,p CPPs),通过Box-Behnken设计建立数学模型,考察关键工艺参数与关键质量属性之间的交互作用,进一步建立养宫方提取工艺的设计空间,并进行空间优化。方差分析显示,所有模型的方差显著(P<0. 01),且失拟值不显著,表明所建模型具有统计学意义,各因素与响应值之间的关系可以用所建的模型进行函数化。最后,通过设计空间的优化,得到养宫方的最佳提取工艺:提取次数为3次,提取时间为122 min,加水倍量为7倍量。该研究基于质量源于设计(QbD)理念开发的养宫方提取工艺稳健可靠,为其制剂的工艺开发及质量控制提供指导。
As an advanced concept in international pharmaceutical research,quality by design( QbD) can fulfill the strategic requirements of drug quality from testing to design. In this paper,the extraction process of Yanggong Prescription which was the modified Siwu Decoction was optimized based on QbD concept. With the extraction amount of solid matter,the content of ferulic acid and the content of paeoniflorin as critical quality attributes( CQAs),the failure mode and effect analysis( FMEA) was used to screen potential critical process parameters( p CPPs). The mathematical model was established by Box-Behnken experimental design to investigate the interaction between critical process parameters( CPPs) and CQAs. Then the design space for the extraction process of Yanggong Prescription was further established and optimized. Analysis of variance showed that the variance of all models was significant( P<0. 01),and the lack-of-fit value was not significant,indicating that the model was statistically significant. The relationship between various factors and the response values could be functionalized by the established models. Finally,through the optimization of the design space,the optimum extraction process of Yanggong Prescription was obtained as follows: 3 extraction times,122 minutes extraction,and 7 times of water adding. The extraction process of Yanggong Prescription based on the QbD concept was robust and reliable,which would provide guidance for the process development and quality control of its formulations.

关键词(KeyWords): 质量源于设计;养宫方;提取工艺;经典名方;设计空间
quality by design;Yanggong Prescription;classical prescription;design space

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81773914);; 国家重点研发计划项目(2018YFC1706900);; 国家“重大新药创制”科技重大专项(2018ZX09201011);; 中华中医药学会青年托举人才项目(QNRC2-A03);; 北京中医药大学中药智能制造与全程质量控制创新团队项目(2019-JYB-TD011)

作者(Author): 黄兴国;张静;杜文慧;江宗岳;杨继;吴志生;
HUANG Xing-guo;ZHANG Jing;DU Wen-hui;JIANG Zong-yue;YANG Ji;WU Zhi-sheng;School of Chinese Materia Medica,Beijing University of Chinese Medicine;Beijing Qihuang Foundation for Scientific Development of Traditional Chinese Medicine;

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DOI: 10.19540/j.cnki.cjcmm.20190410.312

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