确定性筛选设计结合设计空间法优化黄芩提取物的纯化工艺

Definitive screening design combined with design space for optimizing purification process of Scutellariae Radix extract

药典中对黄芩提取物的精制过程许多工艺参数不明确,该研究采用确定性筛选设计结合设计空间法优化黄芩提取物的纯化工艺。首先采用确定性筛选试验,同时研究黄芩提取物的纯化工艺过程中的药液质量分数(X1)、第一次酸沉pH(X2)和第一次保温时间(X3)等9个方法参数对黄芩水提物精制效果的影响。以黄芩苷得率为评价指标,用逐步回归法建立评价指标与方法参数的定量模型,并确定其中3个最关键的影响参数。然后以模拟实验测定误差法计算获得基于达标概率的评价指标与3个关键方法参数之间的设计空间并成功验证。最终所确定的3个关键参数为第二次静置温度,第一次静置温度和第二次酸沉pH。推荐的操作空间为第二次静置温度为5~7℃,第一次静置温度为13~15℃,第二次酸沉pH为1.5~1.7。在此操作空间范围内,黄芩提取物纯化工艺中黄芩苷得率达到80%以上,达标概率达到0.96以上。该研究优选了药典中黄芩提取物纯化工艺的各个参数对黄芩苷得率的影响,为工业生产黄芩提取物提供了参考。

In the pharmacopoeia, many process parameters for the purification process of Scutellariae Radix are unclear. In this study, deterministic screening design combined with design space method was used to optimize the purification process of Scutellariae Radix extract. Nine method parameters such as mass fraction of solution(X1), first acid precipitation pH(X2) and first holding time(X3) in the purification process were firstly studied by definitive screening design. The yield of baicalin was defined as the evaluation index. A stepwise regression method was used then to build quantitative models between evaluation index and method parameters and the three most critical impact parameters were determined. Probability-based design space was calculated and successfully verified with the experimental error simulation method. Finally, the second standing temperature, the first standing temperature and the pH value of the second acid precipitation were determined as the three most critical method parameters. The recommended operating space was as follows: the second standing temperature 5-7 ℃, the first standing temperature 13-15 ℃, and the pH of the second acid precipitation 1.5-1.7. Within this operating space, the baicalin yield in the purification process was over 80%, and the probability of reaching the standard was over 0.96. In this study, we optimized the effect of various parameters for the purification process of the Scutellariae Radix extract in the pharmacopoeia on the yield of baicalin and provided a reference for industrial production of the exact of Scutellariae Radix.