基于Box-Behnken试验设计结合SR-AHP-EWM的经典名方半夏厚朴汤提取工艺研究  

A Study on the Extraction Process of the Classic Formula Banxia Houpo Decoction Based on Box-Behnken Experimental Design and SR-AHP-EWM

作　　者：王龙 杨应莲 闫子轩 范荫荫 吴卫刚 陈伟 周桂芳 李文龙 WANG Long;YANG Ying-lian;YAN Zi-xuan;FAN Yin-yin;WU Wei-gang;CHEN Wei;ZHOU Gui-fang;LI Wen-long(College of Pharmaceutical Engineering of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Haihe Laboratory of Modern Chinese Medicine,Tianjin301617,China;Jiuxin(Wuhan)Institute of Traditional Chinese Medicine Co.,Ltd.,Wuhan 430050,China;Shanghai Zhen Ren Tang Pharmaceutical Co.,Ltd.,Shanghai 200000,China)

机构地区：[1]天津中医药大学中药制药工程学院,天津301617 [2]现代中医药海河实验室,天津301617 [3]九信(武汉)中药研究院有限公司,湖北武汉430050 [4]上海真仁堂药业有限公司,上海200000

出　　处：《分析测试学报》2024年第11期1675-1686,共12页Journal of Instrumental Analysis

基　　金：上海市2022年度“科技创新行动计划”生物医药科技支撑专项项目(22S21904600);武汉市科技计划项目(2020020602012116)。

摘　　要：基于质量源于设计理念(QbD),设置浸泡时间、加水倍量和煎煮次数为关键工艺参数并按照Box-Behnken试验设计制备了17个批次半夏厚朴汤冻干样品。将物质基准样品质量设为标准值,通过计算各样品与物质基准的基准关联度(SR),采用主、客观赋权法相结合的方式,即层次赋权法-熵权法(AHP-EWM),确定迷迭香酸、6-姜酚、和厚朴酚与厚朴酚含量、出膏率及指纹图谱相似度5个评价指标的权重分别为0.05、0.11、0.58、0.26、0。经综合评分后,建立了预测数学模型。确定最佳工艺为加6.32倍量水,回流提取1.5 h,提取3次,经重复实验验证该工艺下所得半夏厚朴汤的综合评分为91.09,相对标准偏差(RSD)为2.2%。结果表明所提出的提取工艺稳定可靠,所得产品的质量属性与物质基准接近,可为半夏厚朴汤后续的研究开发和工业化生产奠定基础。This study utilized the material benchmark-based quality,combined with various research methods,to determine the optimal extraction parameters of Banxia Houpo Decoction(BHD).Based on the concept of quality by design(QbD),key process parameters such as extraction time,water-to-material ratio,and number of decoction cycles were set,and 17 batches of freeze-dried samples of Banxia Houpo Decoction were prepared according to Box-Behnken experimental design.Taking the quality of the material-based reference sample as the standard value,through calculating the standard relation(SR)between each sample and the material-based reference,a combined method of subjective and objective weighting,namely analytic hierarchy process-entropy weight method(AHP-EWM),was used to determine the weights of five evaluation indicators:rosmarinic acid,6-gingerol,honokiol and magnolol content,yield rate and fingerprint similarity,which were determined to be 0.05,0.11,0.58,0.26,and 0,respectively.After comprehensive scoring,a predictive mathematical model was established with statistical significance.The optimal process was determined to be adding 6.32 times the amount of water,reflux extraction for 1.5 hours,and extraction for 3 times.Through repeated experiments to verify this process,the comprehensive score of BHD obtained under this process was 91.09 with a relative standard deviation(RSD)of 2.2%.The results indicate that the combination of SR-AHP-EWM method with response surface in optimizing the classical prescription extraction process for BHD ensures stability and reliability in the extraction process,with product quality attributes closely resembling those of the material-based reference.This approach has partially addressed the issue of control difficulty in transitioning from traditional to modern processes in classical prescriptions,laying a foundation for further research and industrial production of BHD while providing insights for studies on other traditional Chinese medicine formulations.

关 键 词：半夏厚朴汤 质量源于设计 提取工艺 基准关联度 层次赋权法 熵权法 响应面法 多指标成分含量 

分 类 号：O657.7[理学—分析化学] R284.2[理学—化学]