色谱 ›› 2021, Vol. 39 ›› Issue (9): 950-957.DOI: 10.3724/SP.J.1123.2021.06021

• 专论与综述 • 上一篇    下一篇

色谱在药物-机体复杂巨系统研究中的应用进展

贾璞1, 边阳阳1, 白亚军1, 孟雪2, 高朔漠1, 赵晔1, 蔡宇杰3, 郑晓晖1,*()   

  1. 1.西北大学, 陕西 西安 710069
    2.陕西省中医药研究院, 陕西 西安 710004
    3.江南大学, 江苏 无锡 214122
  • 收稿日期:2021-06-14 出版日期:2021-09-08 发布日期:2021-09-06
  • 通讯作者: 郑晓晖
  • 作者简介:* Tel:(029)88302686,E-mail: zhengxh318@nwu.edu.cn.
  • 基金资助:
    国家教育部创新团队发展计划(IRT_15R55);国家重大科学仪器设备开发专项(2013YQ170525);陕西省科技厅重点研发计划(2017zqcxl-sf-01-02-01);陕西省科技厅重点研发计划(2017ZDXM-SF-017);国家科技部“重大新药创制”科技重大专项(2009ZX09103-121);国家科技部“重大新药创制”科技重大专项(2009ZXJ09004-81);陕西省教育厅重点实验室科研计划项目(17JS128)

Applications of chromatography in giant complex drug-organism system

JIA Pu1, BIAN Yangyang1, BAI Yajun1, MENG Xue2, GAO Shuomo1, ZHAO Ye1, CAI Yujie3, ZHENG Xiaohui1,*()   

  1. 1. Northwest University, Xi'an 710069, China
    2. Shaanxi Academy of Tradition Chinese Medicine, Xi'an 710004, China
    3. Jiangnan University, Wuxi 214122, China
  • Received:2021-06-14 Online:2021-09-08 Published:2021-09-06
  • Contact: ZHENG Xiaohui
  • Supported by:
    Program for Changjiang Scholars & Innovative Research Team in University(IRT_15R55);National Key Scientific Instrument and Equipment Development(2013YQ170525);Project of China Key Project of Research and Development Plan of Shaanxi(2017zqcxl-sf-01-02-01);Project of China Key Project of Research and Development Plan of Shaanxi(2017ZDXM-SF-017);National Major Scientific and Technological Special Project for “Significant New Drug Development”(2009ZX09103-121);National Major Scientific and Technological Special Project for “Significant New Drug Development”(2009ZXJ09004-81);Key Laboratory Scientific Research Project of Education Department of Shaanxi Provincial Government(17JS128)

摘要:

色谱是一门以分离分析为主,旨在追求复杂事物纯而净的分析化学的重要分支学科。其经过百余年的发展,理论与技术日臻完善,集科学、技术与艺术于一体。近年来,色谱及其与质谱、核磁共振波谱、原子发射光谱等联用技术极大推动了环境、食品、石油化工、生物医药等领域中所涉及复杂体系的研究进展。作为我国传统文化的核心代表,中医药为中国乃至世界人民的健康服务逾千年,从古至今历经上千年临床考验,疗效经久不衰。近年来,中国政府强调继承与创新,加大推进中医药的现代化与国际化。然而中药自身的多成分协同起效复杂性及其与机体时刻新陈代谢变化的复杂性往往相互作用,由此形成了药物-机体复杂巨系统。该复杂巨系统的分析研究是中医药现代化进程的关键瓶颈。色谱的优势在于复杂成分的分离与分析,此恰能为上述复杂巨系统提供技术支撑,色谱及其联用技术已成为推动中医药分子化、数字化、信息化乃至现代化的主流技术。该文综述了色谱及其联用技术在中药复杂体系、复杂生命过程及药物-机体复杂巨系统中的应用进展,介绍了笔者研究团队对中医药现代化的认识、研究思路和研究工作,最后笔者结合对于百年色谱与千年中医药文化之现代化交织的感悟,对色谱技术在此领域的前景做出了展望。

关键词: 色谱, 分离分析, 辨识技术, 药物-机体复杂巨系统, 创新药物, 综述

Abstract:

Chromatography is an important branch of analytical chemistry that focuses on the separation and analysis of complex structures. Following more than 100 years of development and improvement, chromatography theory and technology have gradually become sophisticated. It has become a coalition of science, technology, and art. Recently, chromatography has been successfully used in combination with mass spectrometry, nuclear magnetic resonance spectroscopy, and atomic emission spectroscopy. Chromatography and the combination with other techniques has significantly improved the analysis of complex systems, such as the environment, food, petrochemicals, biological specimens, and medicine. As one of the oldest healing systems, Traditional Chinese Medicine (TCM) has served to maintain the health of people in China and worldwide for thousands of years. Therefore, it has become a core representative of traditional Chinese culture. In the past two years, TCM has been widely used to treat COVID-19, especially in patients with mild symptoms. Recently, Chinese government emphasized the inheritance and innovation of TCM and stepped up efforts to promote its modernization. TCM includes herbal medicine, acupuncture, moxibustion, massage, food therapy, and physical exercise, such as Tai Chi. In most cases, the patients are administered a mixture of TCM formulas containing more than two herbal medicines, resulting in a highly complicated compound mixture. There is no doubt that long-term clinical practices have demonstrated the safety and therapeutic effect of TCM. However, the compound mixture must be simplified to identify the active compounds. This is mainly because of the existence of carcinogenic compounds, pesticides, and heavy metal residues introduced through plantation and production processes. Moreover, enzymes within the human system generate further new compounds in response to the entry of the TCM containing thousands of components. Consequently, the complex TCM and organism systems interact with each other, constituting a giant complex drug-organism system. The analysis of this giant complex system is acknowledged as a key aspect in the modernization process of TCM. In the last 20 years, many studies have been conducted to screen and identify effective compounds in TCM. These effective compounds can be either the original compounds or new metabolic components generated in vivo. All these efforts are aimed at simplifying the components of TCM and elucidating the therapeutic mechanism. It is well known that chromatography can provide technical support for complex systems owing to its unique advantage of outstanding separation and analysis capabilities. Therefore, chromatography and its combination with other technologies have become mainstream technologies for promoting the compilation of molecular structure, information, digitalization, and modernization of TCM. This paper reviews the research and application of chromatography and combination technologies in a giant complex TCM formula-organism system. Furthermore, the authors briefly introduce and summarize the understanding, research ideas, and activities of the authors’ team on the modernization of TCM. “Liang Guanxi” and “He strategy” are proposed as novel strategies for studying the giant complex drug-organism system. A distinguished technology integrated with mathematical model of causal relation, combined receptor chromatography, identification of chemical molecular structure and evaluating of pharmacological activities was established. It was successfully employed to determine the core effector-response substances of “Liang Guanxi” herb pairs in a giant complex drug-organism system. Subsequently, utilizing the proposed technology of Combination of Traditional Chinese Medicine Molecular Chemistry, the author’s team designed and developed four series of innovative drugs. Inspired by the hundred years of chromatography history and thousands of years of TCM culture, the future development of chromatographic technology is expected. Furthermore, the mechanisms of TCM in medical healthcare, prevention, and treatment of diseases are likely be explained through chromatography, leading to a new strategy to realize the molecularization and digitalization of TCM, which is beneficial to the development of original new drugs.

Key words: chromatography, separation and analysis, identification technology, giant complex drug-organism system, innovative drugs, review

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