基于QbD理念的丹参醇提工艺设计空间的建立与验证

目的：建立并验证丹参醇提工艺的设计空间。方法：以隐丹参酮、丹参酮IIA提取率为关键质量属性（CQA），以乙醇浓度、乙醇倍量、煎煮时间为关键工艺参数（CPP），采用中心点复合设计安排实验，基于二次多项式回归模型开发丹参醇提工艺设计空间。结果：方差分析结果显示模型的P值均小于0．05，且失拟值均大于0．1，表明该模型可以较好的描述CQA和CPP之间的关系,设计空间以Overlay plot展示，在加入95％置信区间后，可缩小设计空间范围并提高其可靠性。结论：基于质量源于设计（QbD）理念建立丹参醇提工艺设计空间可以提高工艺过程的稳健性和灵活性。

Establishment and Verification of Design Space of Ethanol Extraction Process of Salvia Miltiorrhiza based on Quality by Design

Objective ：To establish and verify the design space of ethanol extraction process of Salvia miltiorrhiza. Method ：The extraction ratios of cryptotanshinone and Tanshinone IIA are identified as the critical quality attributes （ CQAs）, and ethanol concentration, ethanol amount, decoction time are identified as critical process parameters （ CPPs ）. The central composite design is used for experimental ar-rangements, and the design space of ethanol extraction process of Salvia miltiorrhiza is established based on the quadratic polynomial re-gression model. Result： Since the p - values of both models are less than 0.05 and values of lack of fit are more than 0. 1, the relationship between CQAs and CPPs could be well described by the two models. The reliability of design space, illustrated by overlay plot, is im-proved with the addition of 95% confidence. Conclusion：The robustness and flexibility of Salvia mihiorrhiza ethanol extraction process have been enhanced via the establishment of design space based on the quality by design（ QbD）concept.