注射用益气复脉(冻干)的质量标志物研究
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摘要
注射用益气复脉(冻干)是由红参、麦冬和五味子3味药材精制而成,临床上主要用于治疗冠心病劳累型心绞痛气阴两虚证及冠心病所致慢性左心功能不全II、III级气阴两虚证。根据质量标志物概念,从物质基础、药效、网络药理、药动学及药性等方面对注射用益气复脉(冻干)质量标志物进行预测分析,初步确定人参皂苷Rb1、Rg1、Rf、Rh1、Rc、Rb2、Ro、Rg3及麦冬皂苷C、麦冬苷元-3-O-α-L-吡喃鼠李糖基-(1→2)-β-D-吡喃葡萄糖苷、偏诺皂苷元-3-O-α-L-吡喃鼠李糖基-(1→2)-β-D-吡喃木糖基-(1→4)-β-D-吡喃葡萄糖苷、果糖、五味子醇甲13个成分为质量标志物,并以此为核心建立全程质量控制体系。基于质量标志物对注射用益气复脉(冻干)进行质控方法研究,可以为中药注射剂质量评价提供新的研究思路。
Yiqi Fumai Lyophilized Injection is a modern preparation composed of Panax ginseng,Ophiopogon japonicas,and Schisandra chinensis.Clinically,it is mainly used for the treatment of cardiovascular diseases such as angina pectoris of coronary heart disease and chronic cardiac insufficiency.According to the concept of quality markers(Q-markers),the Q-markers of Yiqi Fumai Lyophilized Injection were predicted and analyzed from the aspects of chemical components,drug effect,network pharmacology,pharmacokinetics,and drug property.Based on the above studies,13 components of ginsenosides Rb1,Rg1,Rf,Rh1,Rc,Rb2,Ro,Rg3,ophiopojaponin C,phiogenin-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside,pennogenin-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl-(1→4)-β-D-glucopyranoside,fructose,and schisandrin A were identified as Q-markers.According to the Q-markers,we established quality system for process control.The study of Yiqi Fumai Lyophilized Injection based on Q-markers can provide new research ideas for quality assessment of traditional Chinese materia medica injection.
Yiqi Fumai Lyophilized Injection is a modern preparation composed of Panax ginseng,Ophiopogon japonicas,and Schisandra chinensis.Clinically,it is mainly used for the treatment of cardiovascular diseases such as angina pectoris of coronary heart disease and chronic cardiac insufficiency.According to the concept of quality markers(Q-markers),the Q-markers of Yiqi Fumai Lyophilized Injection were predicted and analyzed from the aspects of chemical components,drug effect,network pharmacology,pharmacokinetics,and drug property.Based on the above studies,13 components of ginsenosides Rb1,Rg1,Rf,Rh1,Rc,Rb2,Ro,Rg3,ophiopojaponin C,phiogenin-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside,pennogenin-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl-(1→4)-β-D-glucopyranoside,fructose,and schisandrin A were identified as Q-markers.According to the Q-markers,we established quality system for process control.The study of Yiqi Fumai Lyophilized Injection based on Q-markers can provide new research ideas for quality assessment of traditional Chinese materia medica injection.
引文
[1]刘昌孝,陈士林,肖小河,等.中药质量标志物(Q-Marker):中药产品质量控制的新概念[J].中草药,2016,47(9):1443-1457.
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[4]张铁军,许浚,申秀萍,等.基于中药质量标志物(Q-Marker)的元胡止痛滴丸的“性-效-物”三元关系和作用机制研究[J].中草药,2016,47(13):2199-2211.
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[7]杨静,江振作,柴欣,等.中药注射液“Q-markers”的辨析研究--丹红注射液研究实例[J].世界科学技术-中医药现代化,2016,18(12):2056-2061.
[8]王琼珺,谢伟容,邰艳妮,等.基于Q-Marker成分定性与定量的双黄连制剂质量评价[J].中国实验方剂学杂志,2017,23(18):36-46.
[9]Liu C H,Ju A C,Zhou D Z,et al.Simultaneous qualitative and quantitative analysis of multiple chemical constituents in YiQiFuMai injection by ultra-Fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry[J].Molecules,2016,21(5):640-653.
[10]周垚垚,焦燕婷,王彦帅,等.注射用益气复脉(冻干)化学成分的UPLC-Q-TOF/MS分析[J].药物评价研究,2018,41(3):446-450.
[11]李莉,李德坤,鞠爱春.HPLC-ELSD法测定注射用益气复脉(冻干)中钠元素[J].药物评价研究,2018,41(3):489-492.
[12]Xing L,Jiang M,Dong L Y,et al.Cardioprotective effects of the Yi QiFuMai injection and isolated compounds on attenuating chronic heart failure via NF-κB inactivation and cytokine suppression[J].J Ethnopharmacol,2013,148(1):239-245.
[13]Pang L Z,Ju A C,Zheng X J,et al.YiQiFuMai powder injection attenuates coronary artery ligationinducedmyocardial remodeling and heart failure through modulating MAPKs signaling pathway[J].JEthnopharmacol,2017,202:67.
[14]Wang Y Q,Liu C H,Zhang J Q,et al.Protective effects and active ingredients of Yi-Qi-Fu-Mai sterile powder against myocardial oxidative damage in mice[J].JPharmacol Sci,2013,122(1):17-27.
[15]Li F,Tan Y S,Chen H L,et al.Identification of schisandrin as a vascular endothelium protective component in YiQiFuMai powder injection using HUVECs binding and HPLC-DAD-Q-TOF-MS/MSanalysis[J].J Pharmacol Sci,2015,129(1):1-8..
[16]Feng Y Q,Ju A C,Liu C H,et al.Protective effect of the extract of Yi-Qi-Fu-Mai preparationon hypoxia-induced heart injury in mice[J].Chin J Nat Med,2016,14(6):401-406.
[17]Cao G,Ye X,Xu Y,et al.YiQiFuMai powder injection ameliorates blood-brain barrier dysfunction and brain edema afterfocal cerebral ischemia-reperfusion injury in mice[J].Drug Des Dev Ther,2016,10(1):315-325.
[18]Cao G,Zhou H,Jiang N,et al.YiQiFuMai Powder Injection ameliorates cerebral ischemia by inhibiting endoplasmic reticulumb sress-mediated neuronal apoptosis[J].Oxid Med Cell Longev,2016,2016:5493279.
[19]Cao G S,Chen H L,Zhang Y Y,et al.YiQiFuMai powder injection ameliorates the oxygen-glucosedeprivationinduced brain microvascular endothelial barrierdys function associated with the NF-κB and ROCK1/MLCsignalingpathways[J].J Ethnopharmacol,2016,183:18-28.
[20]Tan Y,Li F,Lv Y,et al.Study on the multi-targets mechanism of YiQiFuMai powder injection on cardio-cerebral ischemic diseases based on network pharmacology[J].J Proteom Computat Biol,2014,1(1):1-9.
[21]焦燕婷,周垚垚,陶瑾,等.基于网络药理学的注射用益气复脉(冻干)作用机制研究[J].药物评价研究,2018,41(3):391-398.
[22]Zheng H R,Chu Y,Zhou D Z,et al.Integrated pharmacokinetics of ginsenosides after intravenous administration of YiQiFuMai Powder injection in rats with chronic heart failure by UFLC-MS/MS[J].JChromatogr B,2018,1072:282-289.
[23]赵利斌,王辉,李伟,等.注射用益气复脉(冻干)在正常和慢性心衰大鼠体内的药动学研究[J].药物评价研究,2018,41(3):439-445.
[24]李莉,杨梅,李德坤,等.注射用益气复脉(冻干)味的测定[J].药物评价研究,2018,41(3):469-474.
[25]徐敏,张磊,岳洪水,等.基于近红外光谱分析技术的注射用益气复脉(冻干)红参醇提过程在线监测[J].药物评价研究,2018,41(3):462-468.
[26]徐敏,张磊,岳洪水,等.基于近红外光谱技术和多变量统计过程控制的五味子提取生产过程监测方法[J].中国中药杂志,2017,42(20):3906-3911.
[27]褚延斌,苏小琴,李德坤,等.基于一测多评法对注射用益气复脉(冻干)中9种成分的质量控制研究[J].中草药,2017,48(17):3537-3544.
[28]褚延斌,苏小琴,李德坤,等.基于一测多评法对注射用益气复脉(冻干)中糖类成分的质量控制研究[J].药物评价研究,2018,41(3):451-456.
[29]周丹丹,王蕴华,李凡,等.注射用益气复脉(冻干)的HPLC指纹图谱研究[J].药物分析杂志,2009,29(11):1900-1904.
[30]何珊珊,岳洪水,宋丽丽,等.注射用益气复脉(冻干)HPLC指纹图谱研究[J].药物评价研究,2015,38(4):390-393.
[31]褚延斌,苏小琴,周学谦,等.基于液质指纹图谱和化学模式识别的注射用益气复脉(冻干)质量综合评价研究[J].中草药,2018,49(10):2410-2419.
[2]刘昌孝.从中药资源-质量-质量标志物认识中药产业的健康发展[J].中草药,2016,47(18):3149-3154.
[3]刘昌孝.基于中药质量标志物的中药质量追溯系统建设[J].中草药,2017,48(18):3669-3676.
[4]张铁军,许浚,申秀萍,等.基于中药质量标志物(Q-Marker)的元胡止痛滴丸的“性-效-物”三元关系和作用机制研究[J].中草药,2016,47(13):2199-2211.
[5]张铁军,白钢,陈常青,等.基于“五原则”的复方中药质量标志物(Q-marker)研究路径[J].中草药,2018,49(1):1-13.
[6]Li W,Polachi N,Wang X,et al.A quality marker study on salvianolic acids for injection[J].Phytomedicine,2018,44:138-147.
[7]杨静,江振作,柴欣,等.中药注射液“Q-markers”的辨析研究--丹红注射液研究实例[J].世界科学技术-中医药现代化,2016,18(12):2056-2061.
[8]王琼珺,谢伟容,邰艳妮,等.基于Q-Marker成分定性与定量的双黄连制剂质量评价[J].中国实验方剂学杂志,2017,23(18):36-46.
[9]Liu C H,Ju A C,Zhou D Z,et al.Simultaneous qualitative and quantitative analysis of multiple chemical constituents in YiQiFuMai injection by ultra-Fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry[J].Molecules,2016,21(5):640-653.
[10]周垚垚,焦燕婷,王彦帅,等.注射用益气复脉(冻干)化学成分的UPLC-Q-TOF/MS分析[J].药物评价研究,2018,41(3):446-450.
[11]李莉,李德坤,鞠爱春.HPLC-ELSD法测定注射用益气复脉(冻干)中钠元素[J].药物评价研究,2018,41(3):489-492.
[12]Xing L,Jiang M,Dong L Y,et al.Cardioprotective effects of the Yi QiFuMai injection and isolated compounds on attenuating chronic heart failure via NF-κB inactivation and cytokine suppression[J].J Ethnopharmacol,2013,148(1):239-245.
[13]Pang L Z,Ju A C,Zheng X J,et al.YiQiFuMai powder injection attenuates coronary artery ligationinducedmyocardial remodeling and heart failure through modulating MAPKs signaling pathway[J].JEthnopharmacol,2017,202:67.
[14]Wang Y Q,Liu C H,Zhang J Q,et al.Protective effects and active ingredients of Yi-Qi-Fu-Mai sterile powder against myocardial oxidative damage in mice[J].JPharmacol Sci,2013,122(1):17-27.
[15]Li F,Tan Y S,Chen H L,et al.Identification of schisandrin as a vascular endothelium protective component in YiQiFuMai powder injection using HUVECs binding and HPLC-DAD-Q-TOF-MS/MSanalysis[J].J Pharmacol Sci,2015,129(1):1-8..
[16]Feng Y Q,Ju A C,Liu C H,et al.Protective effect of the extract of Yi-Qi-Fu-Mai preparationon hypoxia-induced heart injury in mice[J].Chin J Nat Med,2016,14(6):401-406.
[17]Cao G,Ye X,Xu Y,et al.YiQiFuMai powder injection ameliorates blood-brain barrier dysfunction and brain edema afterfocal cerebral ischemia-reperfusion injury in mice[J].Drug Des Dev Ther,2016,10(1):315-325.
[18]Cao G,Zhou H,Jiang N,et al.YiQiFuMai Powder Injection ameliorates cerebral ischemia by inhibiting endoplasmic reticulumb sress-mediated neuronal apoptosis[J].Oxid Med Cell Longev,2016,2016:5493279.
[19]Cao G S,Chen H L,Zhang Y Y,et al.YiQiFuMai powder injection ameliorates the oxygen-glucosedeprivationinduced brain microvascular endothelial barrierdys function associated with the NF-κB and ROCK1/MLCsignalingpathways[J].J Ethnopharmacol,2016,183:18-28.
[20]Tan Y,Li F,Lv Y,et al.Study on the multi-targets mechanism of YiQiFuMai powder injection on cardio-cerebral ischemic diseases based on network pharmacology[J].J Proteom Computat Biol,2014,1(1):1-9.
[21]焦燕婷,周垚垚,陶瑾,等.基于网络药理学的注射用益气复脉(冻干)作用机制研究[J].药物评价研究,2018,41(3):391-398.
[22]Zheng H R,Chu Y,Zhou D Z,et al.Integrated pharmacokinetics of ginsenosides after intravenous administration of YiQiFuMai Powder injection in rats with chronic heart failure by UFLC-MS/MS[J].JChromatogr B,2018,1072:282-289.
[23]赵利斌,王辉,李伟,等.注射用益气复脉(冻干)在正常和慢性心衰大鼠体内的药动学研究[J].药物评价研究,2018,41(3):439-445.
[24]李莉,杨梅,李德坤,等.注射用益气复脉(冻干)味的测定[J].药物评价研究,2018,41(3):469-474.
[25]徐敏,张磊,岳洪水,等.基于近红外光谱分析技术的注射用益气复脉(冻干)红参醇提过程在线监测[J].药物评价研究,2018,41(3):462-468.
[26]徐敏,张磊,岳洪水,等.基于近红外光谱技术和多变量统计过程控制的五味子提取生产过程监测方法[J].中国中药杂志,2017,42(20):3906-3911.
[27]褚延斌,苏小琴,李德坤,等.基于一测多评法对注射用益气复脉(冻干)中9种成分的质量控制研究[J].中草药,2017,48(17):3537-3544.
[28]褚延斌,苏小琴,李德坤,等.基于一测多评法对注射用益气复脉(冻干)中糖类成分的质量控制研究[J].药物评价研究,2018,41(3):451-456.
[29]周丹丹,王蕴华,李凡,等.注射用益气复脉(冻干)的HPLC指纹图谱研究[J].药物分析杂志,2009,29(11):1900-1904.
[30]何珊珊,岳洪水,宋丽丽,等.注射用益气复脉(冻干)HPLC指纹图谱研究[J].药物评价研究,2015,38(4):390-393.
[31]褚延斌,苏小琴,周学谦,等.基于液质指纹图谱和化学模式识别的注射用益气复脉(冻干)质量综合评价研究[J].中草药,2018,49(10):2410-2419.