设计空间法研究龙血竭酚类提取物的精制工艺  

Studying on purification technology of Resina Draconis phenol extracts based on design space method

作　　者：张建 张欣 毕宇安[3,2] 徐桂红[3,2] 黄文哲[3,2] 王振中[3,2] 萧伟[1,3,2] 

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]中药制药过程新技术国家重点实验室,江苏连云港222001 [3]江苏康缘药业股份有限公司,江苏连云港222001

出　　处：《中国中药杂志》2017年第18期3546-3552,共7页China Journal of Chinese Materia Medica

基　　金：江苏省科技成果转化项目(BA2013012)

摘　　要：运用质量源于设计(Qb D)理念,采用"设计空间"方法优化龙血竭酚类提取物的精制工艺。首先将龙血素B、7,4'-二羟基黄酮含量及其转移率、总干膏收率等5个指标做为关键质量属性(CQA),采用Plackett-Burman设计实验,发现关键工艺参数(CPP)为碱浓度、碱倍量和碱溶温度。再采用Box-Behnken设计建立CQA和CPP间的数学模型,方差分析显示模型P均小于0.05,失拟值均大于0.05,可以较好的描述CQA和CPP之间的关系。设定龙血素B、7,4'-二羟基黄酮含量及其转移率、总干膏收率5个指标的控制限度,通过Monte Carlo仿真法计算获得基于概率的设计空间并验证。结果表明,优化后的纯化方法能够保证龙血竭酚类提取物精制工艺稳定,有助于提高酚类提取物批次间质量均一性,为生产自动化控制提供数据支撑。The ＂design space＂ method was used to optimize the purification process of Resina Draconis phenol extracts by using the concept of ＂quality derived from design＂ （QbD）. The content and transfer rate of laurin B and 7,4,-dihydroxyflavone and yield of extract were selected as the critical quality attributes （CQA）. Plackett-Burman design showed that the critical process parameters （CPP） were concentration of alkali, the amount of alkali and the temperature of alkali dissolution. Then the Box-Behnken design was used to establish the mathematical model between CQA and CPP. The variance analysis results showed that the P values of the five models were less than 0.05 and the mismatch values were all greater than 0.05, indicating that the model could well describe the relationship between CQA and CPP. Finally, the control limits of the above 5 indicators （content and transfer rate of laurine B and 7,4,-dihydroxyflavone, as well as the extract yield） were set, and then the probability-based design space was calculated by Monte Carlo simulation and verified. The results of the design space validation showed that the optimized purification method can ensure the stability of the Resina Draconis phenol extracts refining process, which would help to improve the quality uniformity between batches of phenol extracts and provide data support for production automation control.

关 键 词：龙血竭酚类提取物 精制工艺 关键工艺参数 关键质量属性 设计空间 

分 类 号：R284.2[医药卫生—中药学]