考虑药材批次间质量差异的银杏叶提取物制备工艺多参数优化研究  

Research on Multi-Parameter Optimization of the Process of Ginkgo biloba Leaf Extract Considering Quality Variations among Raw Material Batches

作　　者：王元远 李今豪 姚建标 刘豪 龚行楚 WANG Yuanyuan;LI Jinhao;YAO Jianbiao;LIU Hao;GONG Xingchu(College of Pharmaceutical Engineering of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 300193;Jinhua Institute of Zhejiang University,Jinhua 321016;Zhejiang Conba Pharmaceutical Co.,Ltd.,Hangzhou 310058;College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058;National Key Lab.of Chinese Medicine Modernization,Hangzhou 310058)

机构地区：[1]天津中医药大学中药制药工程学院,天津300193 [2]浙江大学金华研究院,浙江金华321016 [3]浙江康恩贝制药股份有限公司,浙江杭州310058 [4]浙江大学药学院,浙江杭州310058 [5]现代中药创制全国重点实验室,浙江杭州310058

出　　处：《中国医药工业杂志》2025年第3期378-388,395,共12页Chinese Journal of Pharmaceuticals

基　　金：浙江省科技计划项目(2022C03142)。

摘　　要：采用确定性筛选试验设计优化了银杏叶提取物的制备工艺,考察了多批次银杏叶药材与12个工艺参数的影响。确定工艺评价指标为干物质含量、总黄酮醇苷含量、总萜类内酯含量、总有机酸含量,进而识别出关键原料参数(CMAs)为药材中的异鼠李素含量、银杏内酯C含量和原儿茶酸含量,关键工艺参数(CPPs)为提取乙醇体积分数、水沉体积、洗涤乙醇体积分数、洗涤体积、洗脱体积。建立了CMAs、CPPs与工艺评价指标之间的数学模型。根据风险大小确定了设计空间并推荐了稳健的操作空间。在操作空间内操作能确保银杏叶提取物的质量。该参数优化方法适用于在药材质量批次间存在差异时,制备获得质量较为一致的提取物,具有良好的推广应用前景。This study optimized the preparation process of Ginkgo biloba leaf extract using a deterministic screening experimental design,investigating the impacts of multiple batches of Ginkgo biloba leaf raw materials and 12 process parameters.The process evaluation indexes were determined as dry matter content,total flavonoid glycoside content,total terpenoid lactone content,total organic acid content.Critical material attributes(CMAs)were identified as the contents of isorhamnetin,ginkgolide C,and protocatechuic acid in raw materials.Critical process parameters(CPPs)were identified as the volume fraction of ethanol for extraction,the volume of water used in the water sedimentation,volume fraction of ethanol for washing,washing volume,and elution volume.The mathematical models were established between CMAs,CPPs,and process evaluation indexes.The design space was determined based on the risk level,and a robust operating space was recommended.Operating within the operating space ensures the quality of the Ginkgo biloba leaf extract.The established parameter optimization method is applicable when there are variations in the quality of raw material batches,and it can be used to prepare extracts with more consistent quality,showing promising potential for widespread application.

关 键 词：银杏叶提取物 工艺优化 试验设计 关键原料参数 设计空间 

分 类 号：R917[医药卫生—药物分析学] R284.2[医药卫生—药学]