中成药上市后质量控制研究进展

摘要/Abstract

摘要： 中成药是我国中医药的组成部分，在临床疾病治疗中发挥着不可替代的作用。目前我国尚存在着中医药发展不平衡不充分、中药材质量良莠不齐、中成药上市后再评价质量控制标准亟待规范等问题。中成药质量控制标准能否满足临床需求是影响中医药产业发展的重要问题。随着我国各地中药注射剂安全性再评价及风险评估工作方案的陆续出台，中成药上市后再评价研究的投入和发展日益加强，影响日益深远。中成药上市后再评价是以需求为驱动，逐步深入的过程，也是相关法规逐渐健全的过程。中成药质量控制研究是保障中药产业高质量发展、提高中药市场竞争力的关键。鉴于此，本研究梳理了中成药质量控制研究相关政策背景，从药效和安全性两个维度，并通过分析实际案例，重点分析符合中医药临床特点的中成药质量控制升级策略，探讨中成药上市后质量控制研究成果转化要点，强调应将基础研究与实际生产、应用相结合，旨在为我国中医药卫生体系的发展提供科学客观的依据。

关键词: font-size:medium, ">中成药；上市后；质量控制；研究进展

Abstract: Traditional Chinese patent medicine is an integral part of traditional Chinese medicine (TCM) and plays an irreplaceable role in the treatment of clinical diseases. There are many problems in the development of traditional Chinese patent medicine in China， such as unbalanced and insufficient development， uneven quality of Chinese herbal medicine， and the urgent need to standardize the quality control standards of traditional Chinese patent medicine after they are marketed. Whether the quality control standard of traditional Chinese patent medicine can meet the clinical demand is an important issue affecting the development of Chinese medicine industry. With the introduction of safety re-evaluation and risk assessment of TCM injections in China， the investment and development of post-marketing research on traditional Chinese patent medicine has been increasingly strengthened， and the impact has become increasingly far-reaching. The post-marketing evaluation of proprietary Chinese medicine is a demand-driven and progressive process， and it is also a process in which relevant laws and regulations are gradually improved. The research on quality control of traditional Chinese patent medicine is the key to guarantee the high-quality development of Chinese medicine industry and to improve the competitiveness of traditional Chinese medicine market. In view of this, this study sorted out the relevant policy background of the quality control research of traditional Chinese patent medicine, and through the analysis of actual cases, from the two dimensions of efficacy and safety,focused on analyzing the upgrading strategies of traditional Chinese patent medicine quality control in line with the clinical characteristics of Chinese medicine,and discussed the main points of the transformation of post-marketing quality control research results of traditional Chinese patent medicine,and emphasized that basic research should be combined with actual production and application,in order to provide a scientific and objective basis for the development of traditional Chinese medicine health system in China.

Key words: font-size:medium, ">Traditional Chinese patent medicines；Post-marketing； Quality control；Research progress

中图分类号:

韩立峰, 付志飞, 阮静雅, 张祎, 王涛. 中成药上市后质量控制研究进展[J]. 中国医药导刊, 2022, 24(4): 342-348.

HAN Lifeng, FU Zhifei, RUAN Jingya, ZHANG Yi, WANG Tao. Research Progress on Post-marketing Quality Control of Traditional Chinese Patent Medicine[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2022, 24(4): 342-348.

参考文献

[1]原国家食品药品监督管理局.关于开展中药注射剂安全性再评价工作的通知（国食药监办[2009]28号）[EB/OL].(2009-01-13)[2022-03-12].https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20090113120001613.html.
     [2]原国家食品药品监督管理局.关于印发中药品种保护指导原则的通知（国食药监注[2009]57号）[EB/OL].(2009-02-03)[2022-03-12].https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20090203120001961.html.
     [3]原国家食品药品监督管理局.关于做好中药注射剂安全性再评价工作的通知（国食药监办[2009]359号）[EB/OL].(2009-07-16)[2022-03-12].https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/200907161521 01457.html.
     [4]原国家食品药品监督管理局.关于征求中药注射剂安全性再评价相关技术评价指导原则意见的函（食药监安函[2010]20号）[EB/OL].(2010-03-29)[2022-03-12].https://www.nmpa.gov.cn/xxgk/zhqyj/zhqyjyp/20100329120001327.html.
     [5]中国政府网.中共中央国务院关于促进中医药传承创新发展的意见[EB/OL].(2019-10-26)[2022-03-12].http://www.gov.cn/zhengce/2019-10/26/content_5445336.htm.
     [6]国家药品监督管理局.国家药监局关于促进中药传承创新发展的实施意见（国药监药注〔2020〕27号）[EB/OL].(2020-12-25)[2022-03-12].https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20201225163906151.html.
     [7]中国政府网. 国务院办公厅关于印发“十四五”中医药发展规划的通知（国办发〔2022〕5号）[EB/OL].(2019-10-26)[2022-03-12].http://www.gov.cn/zhengce/content/2022-03/29/content_5682255.htm.
     [8]李鸿彬，李认书. 对上市中成药再评价制度的回顾与思考[J].中草药， 2015， 46(2): 293-296.
     [9]张容容，邵明义，符宇，等. 基于文献计量学阐述中成药治疗原发性肝癌的研究进展[J/OL].中成药:1-6[2022-05-10].http://kns.cnki.net/kcms/detail/31.1368.R.20211021.1013.002.html.
     [10]孙昱，徐敢，汪祺.中药二次开发的研究思路探讨[J].中草药，2021，52(13):4107-4113.
     [11]Zhang Y，Yang Y，Ruan J，et al. Isobenzofuranones from the aerial parts of Leontopodium leontopodioides (Wild.) Beauv[J]. Fitoterapia， 2018，124:66-72.
     [12]Mu X，Xu X，Guo X，et al.Identification and characterization of chemical constituents in Dengzhan Shengmai Capsule and their metabolites in rat plasma by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry[J].J Chromatogr B Analyt Technol Biomed Life Sci，2019，1108:54-64.
     [13]Wang D，Fu Z，Xing Y，et al. Rapid identification of chemical composition and metabolites of Pingxiao Capsule in vivo using molecular networking and untargeted data-dependent tandem mass spectrometry[J]. Biomed Chromatogr， 2020， 34:e4882.
     [14]Ren J，Dong H，Han Y，et al.Network pharmacology combined with metabolomics approach to investigate the protective role and detoxification mechanism of Yunnan Baiyao formulation[J]. Phytomedicine， 2020， 77:153266.
     [15]Wang R， Liu H， Shao Y， et al. Sophoridine inhibits human colorectal cancer progression via targeting MAPKAPK2[J]. Mol Cancer Res，2019，17(12):2469-2479.
     [16]Tang X， Zeng J， Dai Z， et al. Identification and characterization of chemical constituents in Qi-Lin pills and their metabolites in rat bio-samples after oral administration using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry[J]. J Pharm Biomed Anal， 2020，188:113402.
     [17]Chen H， Yang F， Fu C， et al. Study on the material basis of Dahuang Zhechong pill of anti-hepatoma effect by promoting vascular normalization[J]. Biomed Chromatogr， 2021: e5303
     [18]Huang W， Zhang Z， Niu L， et al. Rapid discovery of potentially vasodilative compounds from Uncaria by UHPLC/Q-Orbitrap-MS based metabolomics and correlation analysis[J]. J Pharm Biomed Anal， 2021， 206:114384.
     [19]国家药品监督管理局.中药注射剂指纹图谱研究的技术要求（暂行）[J].中成药，2003，10(22):671-672.
     [20]连艳，邓莉娟. 生脉制剂指纹图谱研究进展[J].亚太传统医药，2021，17(10):199-204.
     [21]林芃.复方丹参滴丸的质量与生物活性评价方法分析[J].广西质量监督导报， 2021，(6):122-123.
     [22]胡瑞雪，梁元昊，徐文丽，等. 一测多评法在中药中的应用及研究进展[J]. 药物分析杂志， 2019， 39(11):1968-1979.
     [23]赵倩，冯伟红，张启伟，等. “一测多评”法用于栀子金花丸多成分含量测定的可行性研究[J]. 中国中药杂志， 2014， 39(10):1826-1833.
     [24]唐清，匡艳辉，李雯珊，等. 基于指纹图谱和一测多评（QAMS）法的丹红化瘀口服液质量评价研究[J].中草药， 2022， 53(6):1663-1670.
     [25]邵士川，孙慧清，许伟，等.HPLC一测多评法同时测定胃疡灵颗粒中8种成分的含量[J].药学服务与研究，2022， 22(1):34-38.
     [26]张铁军，白钢，刘昌孝. 中药质量标志物的概念、核心理论与研究方法[J]. 药学学报， 2019， 54(2):187-196.
     [27]Wang C，Feng K，Fu Z，et al.Systematic quality evaluation of Peiyuan Tongnao capsule by offline two-dimensional liquid chromatography/quadrupole-Orbitrap mass spectrometry and adjusted parallel reaction monitoring of quality markers[J]. Anal Bioanal Chem， 2019， 411(29):7747-7760.
     [28]张萌，封亮，贾晓斌.基于生物活性与效应基准的中药质量评价技术发展现状与展望[J]. 世界中医药，2020，15(15):2234-2239.
     [29]曹波，慈志敏，许润春，等.基于抗血小板聚集效价的小金丸质量评价研究[J].中草药，2020，51(5):1251-1256.
     [30]高天红，董培智，朴晋华，等.红花注射液生物活性质量控制方法的建立[J].中国药理学通报，2020， 36(5):727-731.
     [31]张慧，李思雨，冯宏玲，等.基于效应成分指数的双黄连制剂质量控制研究[J].药学学报，2019，54(12):2149-2154.
     [32]Zhu H，Wang X，Wang X，et al.The toxicity and safety of Chinese medicine from the bench to the bedside[J].Journal of Herbal Medicine，2021，28:100450.
     [33]高月.有毒中药的毒效关系研究[J].中国药理学与毒理学杂志，2019，33(9):655-656.
     [34]王亚丹，汪祺，张建宝，等.雷公藤制剂的化学成分及质量研究现状[J].中国中药杂志，2019，44(16):3368-3373.
     [35]孟祥，韩玲.含毒性药材中药复方制剂毒代动力学研究的探讨[J].中国药理学与毒理学杂志，2017， 31(3):210-216.
     [36]羊红玉，刘璐璐，朱丹雁，等. Beagle犬单次口服青木香或冠心苏合胶囊马兜铃酸Ⅰ毒代动力学研究[C]. 中国毒理学会第二届全国中青年学者科技论坛会议论文集. 2007.
     [37]Wang L，Sang M，Liu E，et al.Rapid profiling and pharmacokinetic studies of major compounds in crude extract from Polygonum multiflorum by UHPLC-Q-TOF-MS and UPLC-MS/MS[J]. J Pharm Biomed Anal， 2017， 140:45-61.
     [38]Chen W，Wang P，Chen H，et al.The composition differences between small black beans and big black beans from different habitats and its effects on the processing of Polygonum multiflorum[J]. Phytochem Anal， 2021， 32(5):767-779.
     [39]Xing Y，Yan Z，Li Y，et al.An effective strategy for distinguishing the processing degree of Polygonum multiflorum based on the analysis of substance and taste by LC-MS， ICP-OES and electronic tongue[J].J Pharm Biomed Anal， 2021， 205:114328.
     [40]张长松.中药炮制工艺与质量标准的规范化研究[J]. 临床医药文献电子杂志， 2018， 5(86):195.
     [41]于生，单鸣秋，张爱华，等.中药炮制品质量控制及评价方法研究[J]. 世界科学技术-中医药现代化，2008， 10(6):82-85.
     [42]Parvez MK，Rishi V.Herb-drug interactions and hepatotoxicity[J].Curr Drug Metab，2019，20(4):275-282.
     [43]Alissa EM. Medicinal herbs and therapeutic drugs interactions[J].Ther Drug Monit，2014，36(4):413-422.
     [44]兰志勋，黄晓波，蔡兵，等.麻黄素拮抗异丙酚复合诱导引起的循环功能抑制[J].四川医学， 2000，21(10):852-854.
     [45]邱芸.预注小剂量麻黄碱对全麻诱导期心血管系统的防护作用[J].现代中西医结合杂志，2013， 22(8):891-892.
     [46]Bi Y，Wang X，Ding H，et al.Transporter-mediated natural product-drug interactions[J]. Planta Med， 2022:18. doi: 10.1055/a-1803-1744.
     [47]侯健，孙娥，宋捷，等.肝脏药物代谢酶CYP450与中药肝毒性的关系[J]. 中国中药杂志， 2016， 41(15):2774-2780.
     [48]Xing Y，Wang L，Wang C，et al. Pharmacokinetic studies unveiled the drug-drug interaction between trans-2，3，5，4′-tetrahydroxystilbene-2-O-β-d-glucopyranoside and emodin that may contribute to the idiosyncratic hepatotoxicity of polygoni multiflori radix[J]. J Pharm Biomed Anal， 2019， 164:672-680.
     [49]Wang X，Han L，Li G，et al. From the cover: identification of natural products as inhibitors of human organic anion transporters (OAT1 and OAT3) and their protective effect on mercury-induced toxicity[J]. Toxicol Sci， 2018， 161(2):321-334.
     [50]华海敏.近红外光谱技术在茯苓多糖提取过程中的应用研究[D]. 广东药科大学， 2021.
     [51]唐海姣，匡艳辉，张偲偲，等.复方丹参片丹酚酸B和冰片近红外光谱测定和相关性模型建立[J]. 中国中药杂志， 2018， 43(14):2857-2862.
     [52]Jin Y，Wu Z，Liu X，et al.Near infrared spectroscopy in combination with chemometrics as a process analytical technology (PAT) tool for on-line quantitative monitoring of alcohol precipitation[J]. J Pharm Biomed Anal， 2013， 77:32-39.
     [53]Wang L，Han L，Yu H，et al.Analysis of the constituents in "zhu she yong xue shuan tong" by ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry combined with preparative high performance liquid chromatography[J]. Molecules, 2015， 20(11):20518-20537.
     [54]Wang C，Pang X，Zhu T，et al.Rapid discovery of potential ADR compounds from injection of total saponins from Panax notoginseng using data-independent acquisition untargeted metabolomics[J]. Anal Bioanal Chem， 2022， 414(2):1081-1093.
     [55]中药大品种三七综合开发的关键技术创建与产业化应用荣获2017年度国家科学技术进步二等奖[J].中国现代中药，2018，20(1):2.
     [56]黎鹏程，何清湖，孙贵香，等. 国医大师孙光荣论“中医优势病种”[J].湖南中医药大学学报， 2018， 38(1):1-3.
     [57]吕爱平.疾病证候分类研究—以类风湿关节炎为例[J].中国中西医结合杂志，2019， 39(2):136-139.

快速检索引用检索图表检索高级检索