中药质量标志物的概念、核心理论与研究方法
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摘要
中药质量标志物(Q-marker)是中药质量控制的新概念,自2016年提出后,得到全国业内人士的广泛支持和积极参与,极大地推动了中药质量标志物研究,丰富了质量标志物的研究方法和实验证据。为了进一步提升质量标志物研究水平、规范研究模式、提供理论指导,本文提出中药质量标志物核心理论和研究方法。解析了中药质量标志物的定义和科学内涵,并从质量标志物的"有效性"、"特有性"、"传递与溯源"、"配伍环境"以及"可测性"等五个方面概要阐述了质量标志物的核心理论和研究方法,以期为中药质量标志物研究提供有益的理论和方法指导。
Q-marker is a new concept of quality control for traditional Chinese medicine. Since its introduc‐tion in 2016, it has received extensive support and participation from researchers and manufactures of the entire industry. In order to establishing the research level of quality markers, normative research model, we review the proposed core theory and research methods of Chinese medicine quality markers. The definition and scientific connotation of Chinese medicine quality markers are analyzed. The core theories and research methods of quality markers are summarized from five aspects: "effectiveness", "specificity", "transfer and traceability", "compatibility environment" and "measurability" of quality markers. This paper aims to provide useful theoretical and method‐ological guidance for studying Chinese medicine quality markers.
Q-marker is a new concept of quality control for traditional Chinese medicine. Since its introduc‐tion in 2016, it has received extensive support and participation from researchers and manufactures of the entire industry. In order to establishing the research level of quality markers, normative research model, we review the proposed core theory and research methods of Chinese medicine quality markers. The definition and scientific connotation of Chinese medicine quality markers are analyzed. The core theories and research methods of quality markers are summarized from five aspects: "effectiveness", "specificity", "transfer and traceability", "compatibility environment" and "measurability" of quality markers. This paper aims to provide useful theoretical and method‐ological guidance for studying Chinese medicine quality markers.
引文
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[9]Liu CX,Guo DA,Liu L.Quality transitivity and traceability system of herbal medicine products based on quality markers[J].Phytomedicine,2018,44:247-257.
[10]Li K,Li JF,Su J,et al.Identification of quality markers of Yuanhu Zhitong tablets based on integrative pharmacology and data mining[J].Phytomedicine,2018,44:212-219.
[11]Li W,Polachi N,Wang XY,et al.A quality marker study on salvianolic acids for injection[J].Phytomedicine,2018,44:138-147.
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[14]Bai G,Zhang TJ,Hou YY,et al.From quality markers to data mining and intelligence assessment:a smart quality-evaluation strategy for traditional Chinese medicine based on quality markers[J].Phytomedicine,2018,44:109-116.
[15]Ding GY,Wang YS,Liu AN,et al.From chemical markers to quality markers:an integrated approach of UPLC/Q-TOF,NIRS,and chemometrics for the quality assessment of honeysuckle buds[J].RSC Adv,2017,7:22034-22044.
[16]Zhou MG,Ma XY,Ding GY,et al.Comparison and evaluation of antimuscarinic and anti-inflammatory effects of five Bulbus Fritillariae,species based on UPLC-Q/TOF integrated dualluciferase reporter assay,PCA and ANN analysis[J].JChromatogr B,2017,1041:60-69.
[17]Ding GY,Li BQ,Han YQ,et al.A rapid integrated bioactivity evaluation system based on near-infrared spectroscopy for quality control of Flos Chrysanthemi[J].J Pharm Biomed Anal,2016,131:391-399.
[18]Ding GY,Nie Y,Hou YY,et al.An integrated strategy of marker ingredients searching and near infrared spectroscopy rapid evaluation for the quality control of Chinese eaglewood[J].JPharm Biomed Anal,2015,114:462-470.
[19]Li ZQ,Liu J,Zhang DQ,et al.Nuciferine and paeoniflorin can be quality markers of Tangzhiqing tablet,a Chinese traditional patent medicine,based on the qualitative,quantitative and doseexposure-response analysis[J].Phytomedicine,2018,44:155-163.
[20]Guo R,Zhang XX,Su J,et al.Identifying potential quality markers of Xin-Su-Ning capsules acting on arrhythmia by integrating UHPLC-LTQ-Orbitrap,ADME prediction and network target analysis[J].Phytomedicine,2018,44:117-128.
[21]Wu X,Zhang HB,Fan SS,et al.Quality markers based on biological activity:a new strategy for the quality control of traditional Chinese medicine[J].Phytomedicine,2018,44:103-108.
[22]Zhong Y,Zhu JQ,Yang ZZ,et al.Q-marker based strategy for CMC research of Chinese medicine:a case study of Panax notoginseng saponins[J].Phytomedicine,2018,44:129-137.
[23]Jiang ZZ,Yang J,Wang YF.Discrimination and identification of Q-markers based on'Spider-web'mode for quality control of traditional Chinese medicine[J].Phytomedicine,2018,44:98-102.
[24]Wang XJ,Zhang AH,Kong L,et al.Rapid discovery of qualitymarkers from Kaixin San using chinmedomics analysis approach[J].Phytomedicine,2017.DOI:10.1016/j.phymed.2017.12.014.
[25]He J,Feng XC,Wang K,et al.Discovery and identification of quality markers of Chinese medicine based on pharmacokinetic analysis[J].Phytomedicine,2018,44:182-186.
[26]Chen TB,Zuo YH,Dong GT,et al.An integrated strategy for rapid discovery and identification of quality markers in Guanxin Kangtai preparation using UHPLC-TOF/MS and multivariate statistical analysis[J].Phytomedicine,2018,44:239-246.
[27]Tang ZS,Liu YR,Lv Y,et al.Quality markers of animal medicinal materials:correlative analysis of musk reveals distinct metabolic changes induced by multiple factors[J].Phytomedicine,2018,44:258-269.
[28]Xiong Y,Hu YP,Li F,et al.Promotion of quality standard of Chinese herbal medicine by the integrated and efficacy-oriented quality marker of effect-constituent index[J].Phytomedicine,2018,45:26-35.
[29]Zhang YT,Xiao MF,Liao Q,et al.Application of TQSMpolypharmacokinetics and its similarity approach to ascertain Q-marker by analyses of transitivity in vivo of five candidates in Buyanghuanwu injection[J].Phytomedicine,2018,45:18-25.
[30]Huang BM,Zha QL,Chen TB,et al.Discovery of markers for discriminating the age of cultivated ginseng by using UHPLC-QTOF/MS coupled with OPLS-DA[J].Phytomedicine,2018,45:8-17.
[31]Hou JJ,Cao CM,Xu YW,et al.Exploring lipid markers of the quality of coix seeds with different geographical origins using supercritical fluid chromatography mass spectrometry and chemometrics[J].Phytomedicine,2018,45:1-7.
[32]Liu WL,Zhang XL,Fan SQ,et al.A novel concept of Q-Markers:molecular connectivity index[J].Phytomedicine,2018,45:36-40.
[33]Wang ZQ,Shen J,Li P,et al.Research on quality markers of moutan cortex:quality evaluation and quality standards of Moutan Cortex[J].Chin Herb Med,2017,9:299-300.
[34]Guo DA.Quality marker concept inspires the quality research of traditional Chinese medicines[J].Chin Herb Med,2017,9:1-2.
[35]Zhang TJ,Liu CX.Identification of Chinese materia medica and its chemical biology characterization path on five taste theory[J].Chin Tradit Herb Drugs(中草药),2015,46:1-6.
[36]Feng Y,An MP,Hu JF,et al.Study on the effect of Yuanhu Zhitong dropping pills on contraction of uterus isolated from unpregnancy rats[J].Asia-Pacitic Tradit Med(亚太传统医药),2017,13:3-6.
[37]Feng Y,Zhu ZN,Hu JF,et al.Study on compatibility rationality and comparative advantage of analgesic effect of Yuanhu Zhitong Dropping Pills on dysmenorrhea model[J].Drug Eval Res(药物评价研究),2017,40:917-921.
[38]Feng Y,Hu JF,Di ZQ,et al.Analgesic effect of Yuanhu Zhitong Dropping Pills on experimental migraine in rats induced by nitroglycerin and its mechanism[J].Drugs Clin(现代药物与临床),2016,31:423-426.
[39]Han YQ,Xu J,Gong SX,et al.Chemical constituents and mechanism of Corydalis Rhizoma based on HPLC-QTOF/MSand G protein-coupled receptor analysis[J].Acta Pharm Sin(药学学报),2016,51:1302-1308.
[40]Han YQ,Xu J,Zhang XM,et al.Network pharmacology-based study on mechanism of Yuanhu Zhitong Dropping Pills in the treatment of primary dysmenorrhea[J].Acta Pharm Sin(药学学报),2016,51:380-387.
[2]Zhang TJ,Bai G,Han YQ,et al.The method of quality marker research and quality evaluation of traditional Chinese medicine based on drug properties and effect characteristics[J].Phytomedicine,2018,44:204-211.
[3]Zhang HB,Wu X,Xu J,et al.The comparative pharmacokinetic study of Yuanhu Zhitong prescription based on five qualitymarkers[J].Phytomedicine,2018,44:148-154.
[4]Zhang TJ,Bai G,Chen CQ,et al.Research approaches of quality marker(Q-marker)of Chinese materia medica formula based on"five principles"[J].Chin Tradit Herb Drugs(中草药),2018,49:1-13.
[5]Zhang TJ,Wang J,Chen CQ,et al.Method of quality marker research and quality evaluation of Chinese materia medica based on drug properties and effect characteristics[J].Chin Tradit Herb Drugs(中草药),2017,48:1051-1060.
[6]Zhang TJ,Xu J,Shen XP,et al.Relation of"property-responsecomponent"and action mechanism of Yuanhu Zhitong Dropping Pills based on quality marker(Q-Marker)[J].Chin Tradit Herb Drugs(中草药),2016,47:2199-2211.
[7]Liu CX.Determination of quality markers is basis for establishing quality standard and control of Chinese herbal medicines[J].Chin Herb Med,2017,9:299-300.
[8]Liu CX,Cheng YY,Guo DA,et al.A new concept on quality marker for quality assessment and process control of Chinese medicines[J].Chin Herb Med,2017,9:3-13.
[9]Liu CX,Guo DA,Liu L.Quality transitivity and traceability system of herbal medicine products based on quality markers[J].Phytomedicine,2018,44:247-257.
[10]Li K,Li JF,Su J,et al.Identification of quality markers of Yuanhu Zhitong tablets based on integrative pharmacology and data mining[J].Phytomedicine,2018,44:212-219.
[11]Li W,Polachi N,Wang XY,et al.A quality marker study on salvianolic acids for injection[J].Phytomedicine,2018,44:138-147.
[12]Li YB,Zhang YN,Wang YM,et al.A strategy for the discovery and validation of toxicity quality marker of Chinese medicine based on network toxicology[J].Phytomedicine,2018.DOI:10.1016/j.phymed.2018.01.018.
[13]Yang WZ,Zhang YB,Wu WY,et al.Approaches to establish Q-markers for the quality standards of traditional Chinese medicines[J].Acta Pharm Sin B,2017,7:439-446.
[14]Bai G,Zhang TJ,Hou YY,et al.From quality markers to data mining and intelligence assessment:a smart quality-evaluation strategy for traditional Chinese medicine based on quality markers[J].Phytomedicine,2018,44:109-116.
[15]Ding GY,Wang YS,Liu AN,et al.From chemical markers to quality markers:an integrated approach of UPLC/Q-TOF,NIRS,and chemometrics for the quality assessment of honeysuckle buds[J].RSC Adv,2017,7:22034-22044.
[16]Zhou MG,Ma XY,Ding GY,et al.Comparison and evaluation of antimuscarinic and anti-inflammatory effects of five Bulbus Fritillariae,species based on UPLC-Q/TOF integrated dualluciferase reporter assay,PCA and ANN analysis[J].JChromatogr B,2017,1041:60-69.
[17]Ding GY,Li BQ,Han YQ,et al.A rapid integrated bioactivity evaluation system based on near-infrared spectroscopy for quality control of Flos Chrysanthemi[J].J Pharm Biomed Anal,2016,131:391-399.
[18]Ding GY,Nie Y,Hou YY,et al.An integrated strategy of marker ingredients searching and near infrared spectroscopy rapid evaluation for the quality control of Chinese eaglewood[J].JPharm Biomed Anal,2015,114:462-470.
[19]Li ZQ,Liu J,Zhang DQ,et al.Nuciferine and paeoniflorin can be quality markers of Tangzhiqing tablet,a Chinese traditional patent medicine,based on the qualitative,quantitative and doseexposure-response analysis[J].Phytomedicine,2018,44:155-163.
[20]Guo R,Zhang XX,Su J,et al.Identifying potential quality markers of Xin-Su-Ning capsules acting on arrhythmia by integrating UHPLC-LTQ-Orbitrap,ADME prediction and network target analysis[J].Phytomedicine,2018,44:117-128.
[21]Wu X,Zhang HB,Fan SS,et al.Quality markers based on biological activity:a new strategy for the quality control of traditional Chinese medicine[J].Phytomedicine,2018,44:103-108.
[22]Zhong Y,Zhu JQ,Yang ZZ,et al.Q-marker based strategy for CMC research of Chinese medicine:a case study of Panax notoginseng saponins[J].Phytomedicine,2018,44:129-137.
[23]Jiang ZZ,Yang J,Wang YF.Discrimination and identification of Q-markers based on'Spider-web'mode for quality control of traditional Chinese medicine[J].Phytomedicine,2018,44:98-102.
[24]Wang XJ,Zhang AH,Kong L,et al.Rapid discovery of qualitymarkers from Kaixin San using chinmedomics analysis approach[J].Phytomedicine,2017.DOI:10.1016/j.phymed.2017.12.014.
[25]He J,Feng XC,Wang K,et al.Discovery and identification of quality markers of Chinese medicine based on pharmacokinetic analysis[J].Phytomedicine,2018,44:182-186.
[26]Chen TB,Zuo YH,Dong GT,et al.An integrated strategy for rapid discovery and identification of quality markers in Guanxin Kangtai preparation using UHPLC-TOF/MS and multivariate statistical analysis[J].Phytomedicine,2018,44:239-246.
[27]Tang ZS,Liu YR,Lv Y,et al.Quality markers of animal medicinal materials:correlative analysis of musk reveals distinct metabolic changes induced by multiple factors[J].Phytomedicine,2018,44:258-269.
[28]Xiong Y,Hu YP,Li F,et al.Promotion of quality standard of Chinese herbal medicine by the integrated and efficacy-oriented quality marker of effect-constituent index[J].Phytomedicine,2018,45:26-35.
[29]Zhang YT,Xiao MF,Liao Q,et al.Application of TQSMpolypharmacokinetics and its similarity approach to ascertain Q-marker by analyses of transitivity in vivo of five candidates in Buyanghuanwu injection[J].Phytomedicine,2018,45:18-25.
[30]Huang BM,Zha QL,Chen TB,et al.Discovery of markers for discriminating the age of cultivated ginseng by using UHPLC-QTOF/MS coupled with OPLS-DA[J].Phytomedicine,2018,45:8-17.
[31]Hou JJ,Cao CM,Xu YW,et al.Exploring lipid markers of the quality of coix seeds with different geographical origins using supercritical fluid chromatography mass spectrometry and chemometrics[J].Phytomedicine,2018,45:1-7.
[32]Liu WL,Zhang XL,Fan SQ,et al.A novel concept of Q-Markers:molecular connectivity index[J].Phytomedicine,2018,45:36-40.
[33]Wang ZQ,Shen J,Li P,et al.Research on quality markers of moutan cortex:quality evaluation and quality standards of Moutan Cortex[J].Chin Herb Med,2017,9:299-300.
[34]Guo DA.Quality marker concept inspires the quality research of traditional Chinese medicines[J].Chin Herb Med,2017,9:1-2.
[35]Zhang TJ,Liu CX.Identification of Chinese materia medica and its chemical biology characterization path on five taste theory[J].Chin Tradit Herb Drugs(中草药),2015,46:1-6.
[36]Feng Y,An MP,Hu JF,et al.Study on the effect of Yuanhu Zhitong dropping pills on contraction of uterus isolated from unpregnancy rats[J].Asia-Pacitic Tradit Med(亚太传统医药),2017,13:3-6.
[37]Feng Y,Zhu ZN,Hu JF,et al.Study on compatibility rationality and comparative advantage of analgesic effect of Yuanhu Zhitong Dropping Pills on dysmenorrhea model[J].Drug Eval Res(药物评价研究),2017,40:917-921.
[38]Feng Y,Hu JF,Di ZQ,et al.Analgesic effect of Yuanhu Zhitong Dropping Pills on experimental migraine in rats induced by nitroglycerin and its mechanism[J].Drugs Clin(现代药物与临床),2016,31:423-426.
[39]Han YQ,Xu J,Gong SX,et al.Chemical constituents and mechanism of Corydalis Rhizoma based on HPLC-QTOF/MSand G protein-coupled receptor analysis[J].Acta Pharm Sin(药学学报),2016,51:1302-1308.
[40]Han YQ,Xu J,Zhang XM,et al.Network pharmacology-based study on mechanism of Yuanhu Zhitong Dropping Pills in the treatment of primary dysmenorrhea[J].Acta Pharm Sin(药学学报),2016,51:380-387.