吴志生;石涵芬;曾敬其;张静;廖源;黄兴国;郑燕飞;王济;王琦;
WU Zhi-sheng;SHI Han-fen;ZENG Jing-qi;ZHANG Jing;LIAO Yuan;HUANG Xing-guo;ZHENG Yan-fei;WANG Ji;WANG Qi;Beijing University of Chinese Medicine;College of Pharmacy,Fujian University of Traditional Chinese Medicine;College of Pharmacy,Shaanxi University of Chinese Medicine;

• 1:北京中医药大学
• 2:福建中医药大学药学院
• 3:陕西中医药大学药学院

摘要(Abstract)：

复方中药的质量稳定是其疗效稳定的前提和基础。该研究基于质量源于设计(quality by design,QbD)理念,以脱敏定喘方提取工艺中可控性较强的提取次数,提取时间,水倍量为关键工艺参数(critical process parameters,CPPs),采用正交试验从固体物质提取量、苦杏仁苷含量、升麻素苷含量与5-O-甲基维斯阿米醇苷含量4项潜在的关键质量属性(potential critical quality attributes,p CQAs)中筛选CPPs所对应的CQAs。经Box-Behnken试验方差分析确定固体物质提取量与苦杏仁苷含量为提取工艺的CQAs。基于提取工艺的CQAs与CPPs间一项式关系模型得到的最优提取工艺为加水浸泡30 min,提取3次,每次提取100 min,水倍量为10。针对固体物质提取量与苦杏仁苷含量建立控制空间,能同时控制苦杏仁苷含量与固体物质提取量达到优化目标。成型工艺以脱敏定喘颗粒的成型率为CQA,在单因素考察的基础上,确定干膏粉与辅料比例、乙醇比例为CPPs,采用中心点复合设计(central composite design,CCD)优化脱敏定喘颗粒的成型工艺为,以糊精为填充剂,干膏粉-糊精为1∶1,加入0. 3 m L·g-1的70%乙醇作为黏合剂,软材及颗粒状态符合实际生产要求。
The quality of compound traditional Chinese medicine is the prerequisite and foundation for its stable efficacy. Based on the quality by design( QbD) concept,the controllable extraction times,extraction time and the ratio of water were the critical process parameters( CPPs) in the Tuomin Dingchuan Prescription extraction process. The CQAs corresponding to CPPs were screened from the four potential critical quality attributes( p CQAs),namely the extraction amount of solid matter,the content of amygdalin,the content of cimicifugoside and the content of 5-O-methylvisammioside by orthogonal experiment. The extraction amount of solid matter and the content of amygdalin were determined as CQAs in the extraction process by the variance analysis of Box-Behnken experimental. The optimal extraction process based on the linear model between CQAs and CPPs of the extraction process was immersion in water for 30 minutes,extraction for three times,extraction for 100 minutes each time and 10 times of water volume. The control space was established for the extraction amount of solid matter and the content of amygdalin,and both of them could be controlled simultaneously to achieve the optimization objective. The molding ratio of Tuomin Dingchuan granules was regarded as CQA in forming process. On the basis of the single factor investigation,the ratio of dry extract powder to excipient and the ratio of ethanol were determined as CPPs. The central composite design( CCD) was used to optimize the forming process of Tuomin Dingchuan granules. The results showed that the dextrin was used as the filler; the ratio of dry paste to dextrin was 1 ∶1; and 0. 3 m L·g-1 of 70% ethanol was added as binder. The soft material and granules conformed to the actual production requirements.

关键词(KeyWords)： QbD;脱敏定喘颗粒;制备工艺;经典名方;质量控制
QbD;Tuomin Dingchuan Prescription;preparation process;classic prescription;quality control

Abstract:

Keywords:

基金项目(Foundation): 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);; 国家自然科学基金项目(81773914);; 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);; 中华中医药学会青年托举人才项目(QNRC2-A03)

作者(Author): 吴志生;石涵芬;曾敬其;张静;廖源;黄兴国;郑燕飞;王济;王琦;
WU Zhi-sheng;SHI Han-fen;ZENG Jing-qi;ZHANG Jing;LIAO Yuan;HUANG Xing-guo;ZHENG Yan-fei;WANG Ji;WANG Qi;Beijing University of Chinese Medicine;College of Pharmacy,Fujian University of Traditional Chinese Medicine;College of Pharmacy,Shaanxi University of Chinese Medicine;

Email:

DOI: 10.19540/j.cnki.cjcmm.20190629.308

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