补阳还五汤11种成分的药物动力学与谱动学关系研究  

Relationship between polypharmacokinetics and chromatopharmacokinetics of 11 components in Buyang Huanwu Decoction

作　　者：贺琪珺 周燕子 肖美凤[2,3,4,5,6] 王敏存 邓凯文 贺福元[1,2,3,4,5,6] 陈新宇 HE Qijun;ZHOU Yanzi;XIAO Meifeng;WANG Mincun;DENG Kaiwen;HE Fuyuan;CHEN Xinyui(The First Hospital of Hunan University of Chinese Medicine,Changsha,Hunan 410007,China;School of Pharmacy,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;Hunan Key Laboratory of Druggability and Preparation for Chinese Medicine,Changsha,Hunan 410208,China;Engineering Technology Laboratory of Processing and Preparation for Chinese Medicine,Hunan University of Chinese Medicine,Changsha,Hunan 410208;Laboratory of Supramolecular Mechanism and Mathematic-Physics Characterization of Chinese Medicine,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;Key Laboratory of Property and Efficacy of Chinese Medicinal,National Administration of Chinese Medicine,Changsha,Hunan 410208,China)

机构地区：[1]湖南中医药大学第一附属医院,湖南长沙410007 [2]湖南中医药大学药学院,湖南长沙410208 [3]湖南中医药大学中药成药性与制剂制备湖南省重点实验室,湖南长沙410208 [4]湖南中医药大学中药炮制与制剂制备工程技术实验室,湖南长沙410208 [5]湖南中医药大学中医药超分子机理与数理特征化实验室,湖南长沙410208 [6]中药药性与药效国家中医药管理局重点实验室,湖南长沙410208

出　　处：《湖南中医药大学学报》2024年第5期791-801,共11页Journal of Hunan University of Chinese Medicine

基　　金：国家自然科学基金项目(82274215,81874507);湖南省重点研发计划(2022SK2014);湖南省自然科学基金项目(2022JJ30453);湖南省科药联合基金项目(2021JJ80058);全国名老中医药专家陈新宇传承工作室建设项目(国中医药人教函[2022]75号)。

摘　　要：目的阐明中药复方药物动力学与谱动学总量统计矩的数学模型与参数关系,示范性地用补阳还五汤中11种成分进行药物动力学与谱动学研究,探讨其量-时关系,包括代谢时间和色谱保留时间关系。方法采用HPLC/MS法测定补阳还五汤中黄芪甲苷等11种成分的药物浓度,并根据已建立的中药药物动力学与谱动学的总量统计矩数学模型,计算药物动力学与谱动学参数。结果补阳还五汤中11种成分的药物动力学总量统计矩参数分别为AUCT为432.9 ng·h·m L^(-1),MRTT为2.185 h,VRTT为5.259 h2;CLT为82.95 m L·h^(-1);VT为139.9 m L;95%的代谢时间区间为[0,6.680]h。谱动学的VUCT为457.5 ng·h·min·m L^(-1);MCRTT为5.625 min;VCRTT为7.949 min2,95%的时间区间为[0.09898,11.15]min。各取样点的谱动学总量零、一、二阶矩的RSD分别为86.09%、2.299%、7.587%,相似度基本上都在0.875以上。结论中药药物动力学与谱动学总量统计矩法能表征多成分代谢的量-时关系,其中谱动学还能表征所测定代谢成分的构成比的变化和色谱学特征,可为临床合理用药奠定理论与实验研究基础。Objective To elucidate the mathematical model and parameter relationship of the total statistical moment between polypharmacokinetics and chromatopharmacokinetics of the Chinese medicine compound formulas,to demonstrate the polypharmacokinetics and chromatopharmacokinetics study of 11 components in Buyang Huanwu Decoction(BYHWD),and to explore their dose-time relationship,including the metabolic time and chromatographic retention time.Methods HPLC/MS was used to determine the concentrations of 11 components such as astragaloside IV in BYHWD,and the polypharmacokinetic and chromatopharmacokinetic parameters were calculated based on the established total statistical moment mathematical model of Chinese medicine.Results The total moment parameters of polypharmacokinetics of AUCT,MRTT,VRTT,CLT,and VT of the 11 components in BYHWD were 432.9 ng·h·mL^(-1),2.185 h,5.259 h2,82.59 mL·h^(-1),and 139.9 mL respectively,and the 95%metabolic time interval was from 0 to 6.680 h.The total moment parameters of chromatopharmacokinetics of VUCT,MCRTT,and VCRTT were 457.5 ng·h·min·mL^(-1),5.625 min,and 7.949 min^(2)respectively,with a 95%time interval from 0.09898 to 11.15 min.The RSD of the total zero,first,and second moments of chromatopharmacokinetics at each sampling time-point were 86.09%,2.299%,and 7.587%respectively,with the similarity basically above 0.875.Conclusion The total statistical moment method of polypharmacokinetics and chromatopharmacokinetics of Chinese medicine can represent the dose-time relationship of multi-component metabolism.Among them,the chromatopharmacokinetics can also represent the compositional changes and chromatographic characteristics of the measured metabolic components,laying a theoretical and experimental research foundation for clinical rational medication.

关 键 词：补阳还五汤 药物动力学 谱动学 总量统计矩 量-时关系 

分 类 号：R284.1[医药卫生—中药学] R285.5[医药卫生—中医学]