目的 采用网络药理学和设计空间法优化北刘寄奴-骨碎补的提取工艺，确定其提取工艺参数范围，提高原药材利用率，减少能源损耗，以达到减少碳排放量和保护环境的目的。方法 利用网络药理学方法筛选出活性成分，同时结合《中国药典》2020年版一部相关北刘寄奴、骨碎补项下确定柚皮苷、木犀草素为指标性成分，采用Minitab 17软件进行Plackett-Burman实验设计，初步确定提取次数、提取时间以及加溶媒倍数为关键工艺参数（critical process parameters，CPP），通过软件Design-Expert 10进行Box-Behnken 3因素3水平实验设计，建立关键质量属性（critical quality attribute，CQA）和CPP间的数学模型，最后通过Monte Carlo法计算获得基于概率的设计空间，并对点内、点外进行验证。结果 确定最佳提取工艺为乙醇体积分数45%，提取次数3次，每次提取时间2～3 h，加溶媒倍数为11～15倍。结论 运用设计空间法优化北刘寄奴-骨碎补提取工艺所得到的理论值与预测值结果接近，表明该法稳定可靠，可避免常规设计方法潜在的过度提取弊端，在大生产中可以节约资源和减少碳排放。

Objective To optimize the extraction process of Beiliujinu (Siphonostegiae Herba, SH)-Gushibu (Drynariae Rhizoma, DR) by network pharmacology and design space method, determine the range of extraction process parameters, improve the utilization rate of raw medicinal materials and reduce energy consumption, so as to reduce carbon emissions and protect the environment. Methods The active components were screened by network pharmacology, and naringin and luteolin were determined as the index components under the relevant items of “Chinese Pharmacopoeia” 2020 edition. The Plackett-Burman experimental design was carried out by Minitab 17 software. The extraction times, extraction time and solvent multiple were preliminarily determined as the critical process parameters (CPP). The Box-Behnken three-factor three-level experimental design was carried out by software Design-Expert 10, and the mathematical model between the critical quality attribute (CQA) and CPP was established. Finally, the probability-based design space was obtained by Monte Carlo method, and the interior and exterior points were verified.Results The optimal extraction process was determined as follows: ethanol concentration 45%, extraction three times, extraction time 2—3 h each time, and solvent multiple 11—15 times. Conclusion The verification results show that the theoretical value obtained by using the design space method to optimize the extraction process of SH-DR is close to the predicted value, indicating that the method is stable and reliable, which can avoid the potential excessive extraction drawbacks of conventional design methods, and can save resources and reduce carbon emissions in mass production.

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四川省科技创新苗子工程资助项目（2021054）；2021年四川省大学生创业训练计划项目（S202111079126X）；2021年四川省大学生创新训练计划项目（S202111079087）；四川省2021—2023年高等教育人才培养质量和教学改革项目（JG2021-1106）