Abstract: A design space of the reflux extraction process of Sophora Flavescentis Radix-Glycyrrhizauralensis was established and verified following the concept of "quality by design (QbD)". The extraction ratios of total alkaloids of Sophora flavescens(TASF),matrine(MT),and oxymatrine(OMT) were set as the critical quality attributes(CQAs). Based on the single factor experiment,the high and low levels of different parameters used in Plackeet-Burmann design were identified. The amount of Glycyrrhizauralensis and ethanol concentration and extraction temperature were identified as critical parameters(CPPs) using Plackeet-Burmann design. The central composite design was used for experimental arrangements,and the design space of ethanol extraction process was established based on the quadratic polynomial regression model. According to the verification results,the robustness of the reflux extraction process of the active ingredients of Sophora Flavescentis Radix can be guaranteed by operating within the design space parameters. The recommended operation space of parameters were:Glycyrrhizauralensis mass of 10.00g-10.50g,ethanol concentration of 65%-68% and extraction temperature of 94.5-95.0℃.

Key words: quality by design(QbD), total alkaloids, matrine, oxymatrine, optimization, extraction process

摘要： 遵循"质量源于设计（quality by design，QbD）"理念，建立苦参甘草中有效成分的回流醇提工艺的设计空间并验证。以苦参总碱（total alkaloids of Sophora flavescens，TASF）、苦参碱（matrine，MT）及氧化苦参碱（oxymatrine，OMT）的提取率为关键质量属性（critical quality attributes，CQAs），通过单因素实验确定Plackeet-Burmann设计（Plackeet-Burmann design，PBD）中各因素的高低水平，后采用PBD实验确定乙醇体积分数、甘草用量和提取温度为关键工艺参数（critical process parameters，CPPs），再通过中心点复合实验设计优化CPPs，基于二次多项式建立CPPs和CQAs间的数学模型，计算获得设计空间。验证结果表明，在设计空间内操作能够保证苦参有效成分提取工艺品质稳定。最终获得的操作空间为：甘草用量10.00~10.50g，乙醇体积分数65%~68%，提取温度94.5~95.0℃。

关键词: 质量源于设计, 总生物碱, 苦参碱, 氧化苦参碱, 优化, 提取工艺