CN112382363B - 一种中药复方质量标志物的筛选方法 - Google Patents
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Abstract
本发明公开了一种中药复方质量标志物的筛选方法，它包括以下步骤：(1)中药复方化学成分库的建立；(2)基于层次分析法‑熵权法对中药复方质量标志物量化辨识；(3)中药复方质量标志物‑君臣佐使‑药性”网络构建。本发明以有效性为核心，以可测性和特有性为条件，复方中药结合配伍关系，遴选确认中药质量标志物，进而考察其传递与溯源的功能属性，并通过整合AHP法与EWM法围绕中药相应成分的有效性、可测性及特有性3个核心属性项及项下指标进行权重分析，综合评判其质量标志物。并成功应用于气血和胶囊质量标志物研究，为中药复方质量标志物的量化评价与精准辨识提供新的方法，为有力提升中药复方质量控制水平提供重要支撑。
Description
技术领域
本发明涉及一种中药标志物成分的研究方法，具体涉及一种中药复方质量标志物的筛选方法。
背景技术
中药质量标志物(Q-marker)是中药质量控制的新概念，该概念的提出将中药化学成分与安全性、有效性有机关联，引起了中药学术界、产业界对中药质量标志物的研究模式、方法和示范性研究展开了广泛的学术探讨与科学实践。然而多数研究仅对中药化学成分的有效性、可测性、特有性等进行分析预测，但如何将这些碎片化信息进行有机整合并对其进行量化辨识，以得到中药质量标志物的全貌信息和重要性排序还明显存在短板。
本发明基于层次分析法(AHP)-熵权法(EWM)的中药质量标志物量化辨识体系，并以芍药甘草汤为例，计算整合其所含成分在有效性、可测性与特有性的相应得分进行综合量化评价，最终确定芍药苷、芍药内酯苷、甘草苷及甘草酸等为芍药甘草汤发挥止痛功效的质量标志物。
鉴于气血和胶囊组方药味多而复杂且具多重功效，本发明则基于上述中药质量标志物量化辨识体系，首先对气血和胶囊在疏肝理气、活血化瘀及止痛功效项下的有效成分进行辨识，再结合对应有效成分的可测性和专属性整合分析得到气血和胶囊的候选质量标志物，最终兼顾复方配伍关系确认得到气血和胶囊质量标志物，可气血和胶囊质量标准提升提供证据支撑以及为中药复方质量标志物的量化评价与辨识研究提供新思路。
发明内容
发明目的：本发明的目的是为了解决现有技术的不足，提供一种中药复方质量标志物的筛选方法，可用于中药及其中药复方质量的控制，具有重要意义。
技术方案：为了实现以上目的，本发明所采取的技术方案为：
一种中药复方质量标志物的筛选方法，其特征在于，包括以下步骤：
(1)中药复方化学成分库的建立；
(2)基于层次分析法-熵权法对中药复方质量标志物量化辨识；
(3)中药复方质量标志物-君臣佐使-药性”网络构建。
作为优选方案，以上所述的中药复方质量标志物的筛选方法，包括以下步骤：
(1)将中药复方中的中药分别导入中药系统药理学数据库TCMSPTM(http:// lsp.nwu.edu.cn/index.php)、中医药症候关联数据库SYMMAP(https://www.symmap.org/)和中医药综合数据库TCMID(http://119.3.41.228:8000/tcmid/)，并整合各药分别在三个数据库中所得到的化学成分，即得中药复方化学成分库；
(2)基于层次分析法-熵权法对中药复方质量标志物的量化辨识
借助于中药复方化学成分库围绕各成分有效性、可测性、特有性3个核心属性采用AHP-EWM法进行分析，并结合复方配伍关系综合评判其质量标志物；采用AHP法得到有效性、可测性、特有性一级指标的权重，然后在各一级指标下应用EWM法对有文献及实验数据支撑的二级指标进行分析获得各二级指标权重，最终整合指标层各因素的权重加权计算各成分的评分并排序，即得气中药复方候选质量标志物；再结合中药复方候选质量标志物对应药材的方内占比进一步辨识得到中药复方质量标志物的综合评分排序；
(3)中药复方“中药-质量标志物-君臣佐使-药性”网络构建
将中药复方质量标志物及其对应的中药、药性、君臣佐使等信息分别导入Cytoscape3.6.0，用NetworkAnalyzer插件构建分析中药复方“中药-质量标志物-君臣佐使-药性”网络，探究中药复方质量标志物方内角色及功效取向。
本发明所述的气血和胶囊质量标志物的筛选方法，其特征在于，包括以下步骤：
(1)气血和胶囊化学成分库的建立
将气血和胶囊组方15味中药当归(DG)、赤芍(CS)、川芎(CX)、桃仁(TR)、红花(HH)、桔梗(JG)、牛膝(NX)、枳壳(ZQ)、柴胡(CH)、香附(XF)、乌药(WY)、丹参(DS)、延胡索(YHS)、升麻(SM)和甘草(GC)分别导入中药系统药理学数据库TCMSPTM http://lsp.nwu.edu.cn/ index.php、中医药症候关联数据库SYMMAPhttps://www.symmap.org/和中医药综合数据库TCMIDhttp://119.3.41.228:8000/tcmid/，并整合气血和组方各药分别在三个数据库中所得到的化学成分，即得气血和胶囊化学成分库；
(2)借助于气血和胶囊化学成分库围绕各成分有效性、可测性、特有性3个核心属性采用AHP-EWM法进行分析，并结合复方配伍关系综合评判其质量标志物。首先采用AHP法得到有效性、可测性、特有性一级指标的权重，然后在各一级指标下应用EWM法对有文献及实验数据支撑的二级指标进行分析获得各二级指标权重，最终整合指标层各因素的权重加权计算各成分的评分并排序，即得气血和胶囊候选质量标志物。在此基础上，再结合气血和胶囊候选质量标志物对应药材的方内占比进一步辨识得到气血和胶囊质量标志物的综合评分排序；
(3)气血和胶囊“中药-质量标志物-君臣佐使-药性”网络构建
将气血和胶囊质量标志物及其对应的中药、药性、君臣佐使等信息分别导入Cytoscape 3.6.0，用NetworkAnalyzer插件构建分析气血和胶囊“中药-质量标志物-君臣佐使-药性”网络，探究气血和质量标志物方内角色及功效取向。
作为优选方案，以上所述的气血和胶囊质量标志物的筛选方法，通过TCMSPTM、SYMMAP及TCMID数据库初步获得气血和胶囊组方15味中药相应的化学成分，整合建立气血和胶囊化学成分库，其中DG对应成分263个、CS对应成分170个、CX对应成分316个、TR对应成分101个、HH对应成分213个、JG对应成分138个、NX对应成分179个、ZQ对应成分30个、CH对应成分353个、XF对应成分117个、WY对应成分126个、DS对应成分275个、YHS对应成分107个、SM对应成分187个、GC对应成分369个。
作为优选方案，以上所述的气血和胶囊质量标志物的筛选方法，气血胶囊不同功效项下活性成分的有效性数据如下表：
有益效果：本发明提供的中药复方质量标志物的筛选方法和现有技术相比具有以下优点：
本发明提供的中药复方质量标志物的筛选方法，具有可操作性强，应用范围广泛等优点。本发明以有效性为核心，以可测性和特有性为条件，复方中药结合配伍关系，遴选确认中药质量标志物，进而考察其传递与溯源的功能属性”的发明思路，并且通过整合AHP法与EWM法围绕中药相应成分的有效性、可测性及特有性3个核心属性项及项下指标进行权重分析，综合评判其质量标志物。本发明首次建立了具体的中药质量标志物量化辨识的研究体系及策略。
本发明基于该中药质量标志物量化辨识体系，以复方中成药气血和胶囊不同功效为切入点，计算整合气血和胶囊化学成分在多重有效性(疏肝理气、活血化瘀和止痛)、可测性及专属性等项目下的得分，兼顾其对应中药的方内占比整合分析量化辨识得到气血和胶囊的质量标志物。
本发明以气血和胶囊质量标志物的辨识为例，其有效性数据源自于统计分析气血和胶囊各成分与对应药效之间文献报道数量及其网络药理学研究中的度值，但部分数据有缺失(如疏肝理气功效项下无网络药理学度值)；其特有性数据源自于自建气血和胶囊化学数据库，而每个数据库量的大小也影响了其特有性的准确性。最理想状况下应是各要素的权重由客观性的数值确定，纳入统计范围的文献数据量越大越准确，并选择数据较全的文献，从数据库的结果体现成分特有性的时候，应选择数据库量大，且所含数量均衡的数据库，减小导致结果不准确的因素。
通过构建合理的质量评价体系，能很好的体现中药质量标志物整体性、系统性和可量化的优势，从而对质量标志物进行重要性排序，发挥其在中药质量综合评价方面的作用。本发明为中药质量标志物的量化评价与精准辨识提供了创新思路与方法，为有力提升中药质量控制水平提供了重要支撑。
附图说明
图1气血和胶囊候选质量标志物的综合评分前30的排序。
图2气血和胶囊质量标志物-中药-“君臣佐使”-药性关系网络。
具体实施方式
下面结合具体实施例，进一步阐明本发明，应理解这些实施例仅用于说明本发明而不用于限制本发明的范围，在阅读了本发明之后，本领域技术人员对本发明的各种等价形式的修改均落于本申请所附权利要求所限定的范围。
实施例1
材料与方法
1.1气血和胶囊化学成分库的建立
将气血和胶囊组方15味中药DG、CS、CX、TR、HH、JG、NX、ZQ、CH、XF、WY、DS、YHS、SM、GC分别导入中药系统药理学数据库TCMSPTM(http://lsp.nwu.edu.cn/index.php)、中医药症候关联数据库SYMMAP(https://www.symmap.org/)和中医药综合数据库TCMID(http:// 119.3.41.228:8000/tcmid/)，并整合气血和组方各药分别在三个数据库中所得到的化学成分，即得气血和胶囊化学成分库。
1.2基于AHP-EWM法的气血和胶囊质量标志物量化辨识
借助于气血和胶囊化学成分库围绕各成分有效性、可测性、特有性3个核心属性采用AHP-EWM法进行分析，并结合复方配伍关系综合评判其质量标志物。首先基于对中药质量标志物3个核心要素重要性的认识，采用AHP法得到有效性、可测性、特有性一级指标的权重，然后在各一级指标下应用EWM法对有文献及实验数据支撑的二级指标进行分析获得各二级指标权重，最终整合指标层各因素的权重加权计算各成分的评分并排序，即得气血和胶囊候选质量标志物。在此基础上，再结合气血和胶囊候选质量标志物对应药材的方内占比进一步辨识得到气血和胶囊质量标志物的综合评分排序。
1.3气血和胶囊“中药-质量标志物-君臣佐使-药性”网络构建
将气血和胶囊质量标志物及其对应的中药、药性、君臣佐使等信息分别导入Cytoscape 3.6.0，用NetworkAnalyzer插件构建分析气血和胶囊“中药-质量标志物-君臣佐使-药性”网络，探究气血和质量标志物方内角色及功效取向。
2、实验结果
2.1气血和胶囊化学成分库的建立
通过TCMSPTM、SYMMAP及TCMID数据库初步获得气血和胶囊组方15味中药相应的化学成分，整合建立了气血和胶囊化学成分库，其中DG对应成分263个、CS对应成分170个、CX对应成分316个、TR对应成分101个、HH对应成分213个、JG对应成分138个、NX对应成分179个、ZQ对应成分30个、CH对应成分353个、XF对应成分117个、WY对应成分126个、DS对应成分275个、YHS对应成分107个、SM对应成分187个、GC对应成分369个。
2.2气血和胶囊活性成分有效性的量化评价
质量控制的根本目的是对中药有效性的控制，因此“有效”是质量标志物的核心要素[2]。本研究通过“中国知网”及“pubmed”数据库，检索整理2000年1月至2020年7月之间气血和胶囊活性成分库中各化学成分分别与气血和胶囊主要功效“疏肝理气”、“活血止痛”相关的文献数量(仅纳入实验性研究文献，排除综述类文献、临床个案、病例报告等)、以及结合课题组前期有关气血和胶囊治疗气滞血瘀证网络药理学研究工作，根据各活性成分在各功效项下对应的文献数量与其在网络药理学研究中各功效模块下对应的度值(度值，即网络中连接到节点上边的数量，数值越大表示在网络中越重要)，经标准化、求信息熵、求熵权，获得有效性下二级指标文献数据和实验数据的权重，为气血和胶囊质量标志物辨识提供有效性的科学量化指标。
各效应所对应的活性成分在文献中出现的次数越多，说明该成分与其相应功效越密切，有效性越好，各成分出现的频次如表1所示。度值网络拓扑分析中的重要参数，表示网络中的一个节点所连接关系的数量，度值越大表明成分在所构建的功效网络中越重要(表1)。基于AHP法得到有效性的权重占比为57％，采用EWM法分别计算不同功效项下文献数据和实验数据的权重，疏肝理气功效项下CRH文献数量占比：27％，ACTH文献数量占比：26％，CORT文献数量占比：31％，5-HT文献数量占比：16％；活血化瘀功效项下活血文献数量占比：31.11％，调节凝血功能数量占比33.73％，调节血液流变学度值占比18.38％，调节凝血功能度值占比16.78％；止痛功效项下止痛文献数量占比55.37％，止痛度值占比44.63％。
表1气血胶囊不同功效项下活性成分的有效性数据
2.3气血和胶囊活性成分可测性的量化评价
本发明通过文献检索获得各有效成分含量平均值及并计算成分含量变异系数，基于此作为中药质量标志物的辨识的可测性量化评分数据。本研究通过“中国知网”及“pubmed”数据库，气血和胶囊组方各中药中文名或拉丁名，各中药对应的有效成分英文名，“含量”或“content”组合为关键词，检索整理2000年1月至2020年7月之间的含量信息，纳入实验性研究文献，排除综述类文献、测定入血成分的文献等，以此作为气血和胶囊可测性的数据。气血和胶囊组方各药有效成分平均含量越大，说明含量高，各成分的变异系数，体现该成分在不同批次药材中的变化，若变异系数越大，说明该成分含量更需要限定；基于AHP法得到的可测性权重占比为33％，根据各评价指标包含的原始矩阵，数据见表2，经EWM法计算得到有效成分含量均值、有效成分含量变异性权重系数分别为47.98％和52.02％。
表2气血和胶囊活性成分的可测性数据
2.4气血和胶囊活性成分特有性的量化评价
DG为伞形科植物当归Angelica sinensis(Oliv.)Diels的干燥根，CX是伞形科植物川芎LigusticumchuanxiongHort.的干燥根茎，二者同属一科，有相似的化学成分和药理作用，主要包含芳香酸、苯酞内酯类、多糖类、黄酮类等挥发性成分，其中苯酞内酯类(洋川芎内酯I、洋川芎内酯H等)和芳香酸类成分(阿魏酸等)是DG和CX常用于含量测定及质量控制的活性成分，且苯酞内酯类可作为二者在气血和胶囊中区别于其他药材的特征性成分。CS为毛茛科植物芍药Paeonia lactifloraPall.或川赤芍Paeonia veitchii Lynch的干燥根，主要含有萜类及其苷、黄酮类及其苷、挥发油类等多种化学成分，其中以赤芍总苷(芍药苷、苯甲酰芍药苷、芍药内酯苷等)为特征性成分。TR为蔷薇科植物桃Prunuspersica(L.)Batsch或山桃Prunusdavidiana(Carr.)Franch.的干燥成熟种子，主要成分有脂肪油类、苷类、挥发油类、甾体及其糖苷等，其中以苦杏仁苷、野樱苷等氰苷为特征性成分；HH为菊科红花属植物红花CarthamustinctoriusL.的干燥花，主要成分包括黄酮类、醌式查尔酮苷类、生物碱类、有机酸类等成分，其中以羟基红花黄色素A等为特征性成分；JG是桔梗科植物桔梗Platycodongrandiflorum(Jacq.)A.DC.的干燥根，主要含有齐墩果烷型三萜皂苷、多糖、黄酮类、甾醇类、脂肪酸类及微量元素等，其中桔梗皂苷D等为代表的三萜皂苷为特征性成分；NX为苋科植物牛膝AchyranthesbidentataBL.的干燥根，主要含有三萜皂苷类、甾酮类及多糖类等成分，其中β-蜕皮甾酮、牛膝甾酮等成分为其特征性成分；ZQ为芸香科植物酸橙Citrusaurantium L.及其栽培变种的干燥未成熟果实，主要含有黄酮类、生物碱类、挥发油类及香豆素类等有效成分，其中以柚皮苷、橙皮苷、新橙皮苷等黄酮类成分为特征性成分；CH来源于伞形科植物柴胡BupleurumchinenseDC.和狭叶柴胡BupleurumscorzonerifoliumWilld.的干燥根，主要含三萜皂苷类，挥发油及多糖类成分，其中柴胡皂苷a，c，d等成分为特征性成分；XF为莎草科植物莎草CyperusrotundusL.的干燥根茎，主要包含由多种单萜、倍半萜及其氧化物组成分的挥发油类成分，黄酮类、糖类、生物碱、酚类和三萜类等成分，其中以α-香附酮为代表的等单萜及倍半萜为特征性成分；WY为樟科植物乌药Linderaaggregata(Sims)Kosterm.的干燥块根，主要含挥发油类、异喹啉生物碱、呋喃倍半萜及其内酯、黄酮类等成分，其中以乌药醚内酯、乌药内酯、新乌药内酯等呋喃倍半萜及其内酯类成分为特征性成分；DS为唇形科植物丹参SalviamiltiorrhizaBge.的干燥根和根茎，主要以丹参酮型二萜为主的二萜类脂溶性成分(丹参酮I、丹参酮IIA及隐丹参酮等)和以酚酸为主的水溶性成分(丹酚酸A、丹酚酸B、紫草酸等)为特征性成分，此外还有含氮化合物、内酯类、多糖、黄酮、甾体及三萜类成分；YHS系罂粟科紫堇属植物延胡索CorydalisyanhusuoW.T.Wang的干燥块茎，主要含延胡索甲素、延胡索乙素、黄连碱等为特征性成分；SM为毛茛科植物大三叶升麻Cimicifugaheracleifolia Kom.、兴安升麻Cinicifugadahurica(Turcz.)Maxim.或升麻CimicifugafoetidaL.的干燥根茎，主要含有三萜及其苷类(升麻素和升麻苷等)、酚酸类及其衍生物(如阿魏酸、异阿魏酸、咖啡酸)为特征性成分，此外还有色原酮类、挥发油类等成分。GC为豆科植物甘草GlycyrrhizauralensisFish.、胀果甘草GlycyrrhizainflateBat.或光果甘草Glycyrrhizaglabra L.的干燥根及根茎，主要含酚类、醌类、黄酮类、生物碱、萜类、氨基糖衍生物等，其中甘草酸、甘草苷、甘草次酸、异甘草素等为特征性成分。
在明确中药化学物质组成的前提下，通过化学成分的生源途径及特有性分析，选择具有代表性、特异性的化学成分，可提高中药质量控制的针对性和指向性。基于AHP法得到特有性权重占比为10％，本发明通过统计气血和胶囊相应有效成分在自建气血和胶囊成分库中出现的频次N作为特有性的评价数据，相应有效成分在数据库中出现频次越多，其专属性越差，最终以1/N为相应有效成分的特有性评分。相关数据如表3所示。
表3气血和胶囊活性成分的特有性信息
2.5整合有效性、可测性及特有性的气血和胶囊质量标志物量化辨识
根据气血和胶囊化学成分在有效性、可测性与特有性对应条目下的评分，将基于AHP-EWM法的中药质量标志物量化辨识体系所得到的要素层、次级要素层权重与控制层指标权重相结合得到综合权重值(表4)，再将相应条目下的具体数值与综合权重值相乘后累加，即得整合评分排序，从而发现气血和胶囊的候选质量标志物，图1为气血和胶囊前30个候选质量标志物。
表4结合AHP-EMW法的指标综合权重确定
2.6结合复方配伍环境确认气血和胶囊质量标志物
气血和胶囊组方严格按照“君臣佐使”法则由15味中药组成，其中DG补血活血、调经止痛，CS清血分郁热，凉血消斑为君药，CX和YHS辛散温通、行血中气滞、气中血凝，CH、XF可作用于肝脏缓解“气滞”以达舒肝止痛，TR、HH、DS为血中气药，能泻能补、活血调经、通经利脉，JG宣开肺气，升降气机为臣药，WY散寒理气、调经止痛，ZQ行气宽中，破气除痞，NX活血通经，引血下行为佐药，SM、GC为使药。根据中国专利200410073078.2一种用于治疗女性月经失调(气滞血淤证)的药物，其组方各药的重量配比为DG(～34-50，平均42)、CS(～34-50，平均42)、CX(～34-50，平均42)、CH(～27-40，平均33.5)、YHS(～27-40，平均33.5)、TR(～34-50，平均42)、HH(～27-40，平均33.5)、DS(～27-40，平均33.5)、JG(～27-40，平均33.5)、WY(～22-33，平均27.5)、ZQ(～22-33，平均27.5)、NX(～22-33，平均27.5)、XF(～22-33，平均27.5)、SM(～22-33，平均27.5)、GC(～22-33，平均27.5)，据此气血和胶囊处方重量平均约为500.5，将基于中药质量标志物量化辨识体系所得到的所有候选质量标志物按来源药材的不同分别乘以相应来源药材的重量配比与气血和处方平均重量的比即得气血和胶候选质量标志物的综合评分，其中阿魏酸、槲皮素、咖啡酸、山柰酚、芦丁、藁本内酯、洋川芎内酯I、香草酸、原儿茶酸、绿原酸、洋川芎内酯I、迷迭香酸、洋川芎内酯A、没食子酸、延胡索乙素15个潜在质量标志物的综合得分最高，提示可作为气血和胶囊的质量标志物(表5)。本研究基于Cytoscape3.6.0软件对气血和胶囊前15个质量标志物及其相应中药、“君臣佐使”、药性构建可视化关系从成分层次溯源到中医药理论体系来分析阐明气血和胶囊质量标志物(图2)。
表5气血和胶囊质量标志物(TOP15)的综合评分排序及相关信息
注：DG：当归；CS：赤芍；CX：川芎；CH：柴胡；DS：丹参；TR：桃仁；HH：红花；JG：桔梗；NX：牛膝；WY：乌药；XF：香附；YHS：延胡索；SM：升麻；ZQ：枳壳；GC：甘草
在图2网络中，气血和胶囊15个候选质量标志物对应13味气血和胶囊各组方中药，原方中“君臣佐使”均有涵盖(但缺少臣药桔梗及桃仁，主要由于其对应的成分药效评分太低)。其中阿魏酸具有抗血小板聚集，抑制血小板5-羟色胺释放，抑制血小板血栓素A2的生成，增强前列腺素活性，镇痛，缓解血管痉挛等作用，也作为“君药”当归的质控成分，因此阿魏酸可作为气血和胶囊的代表性成分。槲皮素、山柰酚、芦丁等为简单的黄酮类化合物，虽然专属性不强，但是其不仅具有抗炎、抗菌降血脂等作用还具有扩张冠状动脉、增加冠脉血流量、拮抗血小板活化因子等保护心血管的潜力。咖啡酸是一种在植物界广泛分布的多酚，研究表明咖啡酸具有提高凝血因子的功能、升高白细胞和血小板的作以及显著的抗血栓作用。洋川芎内酯A和I是当归和川芎中的活性成分，文献：GUO L,GONG M X,WU S,etal.Identification and quantification of the quality markers and anti-migraineactive components in Chuanxiong Rhizoma and Cyperi Rhizoma herbal pair basedon chemometric analysis between chemical constituents and pharmacologicaleffects[J].J Ethnopharmacol，2020，246：112228。通过人工神经网络和偏最小二乘法判别分析关联成分-药效得到川芎-香附药对治疗偏头痛的质量标志物为阿魏酸、洋川芎内酯A和I等间接地支撑了本研究的结果。延胡索乙素来自于“臣药”延胡索，可能是气血和胶囊发挥镇痛的作用的主要活性物质[9]。除此之外，气血和胶囊的15个候选质量标志物所对应13味气血和胶囊各组方中药药性均以温、平、微寒为主，当归、川芎、红花、乌药、延胡索性温以达散寒活血化瘀之功佐以性之微寒柴胡、枳壳与平性香附等兼顾疏肝理气之效。
Claims (3)
1.一种中药复方质量标志物的筛选方法，其特征在于，包括以下步骤：
(1)将中药复方中的中药分别导入中药系统药理学数据库TCMSPTMhttp://lsp.nwu.edu.cn/index.php、中医药症候关联数据库SYMMAP https://www.symmap.org/和中医药综合数据库TCMIDhttp://119.3.41.228:8000/tcmid/，并整合各药分别在三个数据库中所得到的化学成分，即得中药复方化学成分库；
(2)基于层次分析法-熵权法对中药复方质量标志物的量化辨识
借助于中药复方化学成分库围绕各成分有效性、可测性、特有性3个核心属性采用AHP-EWM法进行分析，并结合复方配伍关系综合评判其质量标志物；采用AHP法得到有效性、可测性、特有性一级指标的权重，然后在各一级指标下应用EWM法对有文献及实验数据支撑的二级指标进行分析获得各二级指标权重，最终整合指标层各因素的权重加权计算各成分的评分并排序，即得气中药复方候选质量标志物；再结合中药复方候选质量标志物对应药材的方内占比进一步辨识得到中药复方质量标志物的综合评分排序；
(3)中药复方“中药-质量标志物-君臣佐使-药性”网络构建
将中药复方质量标志物及其对应的中药、药性、君臣佐使等信息分别导入Cytoscape3.6.0，用Network Analyzer插件构建分析中药复方“中药-质量标志物-君臣佐使-药性”网络，探究中药复方质量标志物方内角色及功效取向。
2.气血和胶囊质量标志物的筛选方法，其特征在于，包括以下步骤：
(1)气血和胶囊化学成分库的建立
将气血和胶囊组方15味中药当归DG、赤芍CS、川芎CX、桃仁TR、红花HH、桔梗JG、牛膝NX、枳壳ZQ、柴胡CH、香附XF、乌药WY、丹参DS、延胡索YHS、升麻SM和甘草GC分别导入中药系统药理学数据库TCMSPTMhttp://lsp.nwu.edu.cn/index.php、中医药症候关联数据库SYMMAPhttps://www.symmap.org/和中医药综合数据库TCMID http://119.3.41.228:8000/tcmid/，并整合气血和组方各药分别在三个数据库中所得到的化学成分，即得气血和胶囊化学成分库；
(2)借助于气血和胶囊化学成分库围绕各成分有效性、可测性、特有性3个核心属性采用AHP-EWM法进行分析，并结合复方配伍关系综合评判其质量标志物；首先采用AHP法得到有效性、可测性、特有性一级指标的权重，然后在各一级指标下应用EWM法对有文献及实验数据支撑的二级指标进行分析获得各二级指标权重，最终整合指标层各因素的权重加权计算各成分的评分并排序，即得气血和胶囊候选质量标志物；在此基础上，再结合气血和胶囊候选质量标志物对应药材的方内占比进一步辨识得到气血和胶囊质量标志物的综合评分排序；
(3)气血和胶囊“中药-质量标志物-君臣佐使-药性”网络构建
将气血和胶囊质量标志物及其对应的中药、药性、君臣佐使等信息分别导入Cytoscape3.6.0，用Network Analyzer插件构建分析气血和胶囊“中药-质量标志物-君臣佐使-药性”网络，探究气血和质量标志物方内角色及功效取向。
3.根据权利要求2所述的气血和胶囊质量标志物的筛选方法，其特征在于，通过TCMSPTM、SYMMAP及TCMID数据库初步获得气血和胶囊组方15味中药相应的化学成分，整合建立气血和胶囊化学成分库，其中DG对应成分263个、CS对应成分170个、CX对应成分316个、TR对应成分101个、HH对应成分213个、JG对应成分138个、NX对应成分179个、ZQ对应成分30个、CH对应成分353个、XF对应成分117个、WY对应成分126个、DS对应成分275个、YHS对应成分107个、SM对应成分187个、GC对应成分369个。
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