复方中草药进入欧洲市场的关键成功因素

中医药是中国人民为人类贡献的宝贵财富之一。中医药在全球范围内被接受的关键是能够提供基于生物活性成分的质量控制系统作为科学证据的能力。目前现代科学技术完全可以实现中草药全产业链的标准化生产,确保药品的质量、有效性和安全性,从而打入国际市场。中草药以药品的身份进入欧盟有多种途径,但是无论哪一种选择,药物的质量都是最重要的。迄今为止,中草药成分的复杂性和其生物活性协同作用的复杂性,对药物质量控制来说仍然是一个挑战。特别是复方中草药的质量控制难度更大。系统生物学方法是一种多维化学和药理学方法,能够将复杂的中草药成分与生物活性联系起来。因此,系统生物学在中药领域的应用是中草药现代化研究领域的关键组成部分,它可以为中医的诊断和中草药的传统使用提供科学证据,从而大力提高中草药产品在全球的接受度。本文讨论了中草药特别是复方中草药进入欧洲的关键点,强调了质量标准的重要性,以及为保障质量标准的落实,执行不同类型的良好的质量管理(GXP)的重要性。同时,介绍了欧洲对植物药安全性和有效性的理解,以及采取的相应管理方法。此外,本文也为说明中草药在欧盟市场上的商业潜力,介绍了一些欧盟成员国常见疾病的OTC市场的情况,他们是注册中草药进入欧盟的主流市场,我们需要对这样的市场规模有一个准确的了解。     

Traditional Chinese medicine (TCM): are polyphenols and saponins the key ingredients triggering biological activities?

The number of herbal formulae considered to be clinically effective and recorded in the Chinese medical literature is huge. The scientific basis for the remedial effects of these herbal formulae is not yet understood, nor has a clear need been given as to how to make use and combine traditional Chinese medicine (TCM) and Western medicine in an effective way. In this context, it is of interest to ascertain what individual constituents are responsible for the bioactive properties, and thus to extract the common characters of composition of huge formulae to provide a scientific explanation for their modes of action. We consider polyphenols and saponins as the key ingredients in TCM remedies responsible for most of the observed biological effects, reflecting the specific requirements within the TCM philosophy of treatment based on the investigation of its chemical composition.     

Approaches to establish Q-markers for the quality standards of traditional Chinese medicines

Traditional Chinese medicine (TCM) has played a pivotal role in maintaining the health of Chinese people and is now gaining increasing acceptance around the global scope. However, TCM is confronting more and more concerns with respect to its quality. The intrinsic “multicomponent and multitarget” feature of TCM necessitates the establishment of a unique quality and bioactivity evaluation system, which is different from that of the Western medicine. However, TCM is investigated essentially as “herbal medicine” or “natural product”, and the pharmacopoeia quality monographs are actually chemical-markers-based, which can ensure the consistency only in the assigned chemical markers, but, to some extent, have deviated from the basic TCM theory. A concept of “quality marker” (Q-marker), following the “property-effect-component” theory, is proposed. The establishment of Q-marker integrates multidisciplinary technologies like natural products chemistry, analytical chemistry, bionics, chemometrics, pharmacology, systems biology, and pharmacodynamics, etc. Q-marker-based fingerprint and multicomponent determination conduce to the construction of more scientific quality control system of TCM. This review delineates the background, definition, and properties of Q-marker, and the associated technologies applied for its establishment. Strategies and approaches for establishing Q-marker-based TCM quality control system are presented and highlighted with a few TCM examples.     

Development of a novel quality standard of Indigoplant

Traditional Chinese medicine (TCM) has been widely used in China for thousands of years, and has received more and more recognition worldwide. Indigoplant (Folium Polygoni Tinctorii), a TCM, has been used in various diseases. In our study, we established a quality standard of Indigoplant according to the European Pharmacopoeia, and this standard has passed the early audit stages of the European Pharmacopoeia Commission. The Indigoplant samples were identified with high performance thin layer chromatography (HPTLC), qualified with RP-HPLC quantitation, and analyzed with a series of quality tests. An accurate, reliable and robust HPLC method with gradient elution for quantitation was developed and validated with a one-variable-at-a-time (OVAT) robustness approach. Several tests, including the loss on drying, total ash and ash insoluble in hydrochloric acid of Indigoplant, were performed for quality analysis. Furthermore, six batches of the Indigoplant samples were appraised with this quality standard. In conclusion, the established quality standard was more internationally normative and applicable for the quality control of Indigoplant in practical application.     

Clinical studies with traditional Chinese medicine in the past decade and future research and development

Traditional Chinese medicine (TCM) is currently considered a complementary or alternative medical system in most Western countries and has been increasingly accepted worldwide. More and more clinical trials on TCM have been conducted internationally, and scientists worldwide are becoming increasingly interested in the evaluation of clinical efficacy of TCM based on clinical trials. This paper reviews the situation of clinical trials on TCM in the past decade, including systematic reviews about clinical trials either focusing on the treatment of disease with TCM approaches or focusing on one herbal product, conduction of clinical trials on TCM either with randomization and controlled methods or general observation. Some general issues on the conduct of clinical trials on TCM, such as randomization, control, quality of life (QOL), patient reported outcomes (PROs) and biomarkers, quality control, safety evaluation and case studies, are discussed, and accordingly some suggestions are proposed.     

芪苈强心胶囊中强心有效成分及其作用机理的计算机模拟

目的:通过计算机模拟技术研究芪苈强心胶囊中已知结构化合物的分子特征,分析与强心西药分子结构、理化性质相似的中药成分,并寻找比对中西药分子的作用靶点,以期为新药研发或作用机制研究提供思路。方法:通过中西药的分子集构建,进行中西药分子的理化性质分析和结构比对,同时通过反向药效团搜索进行中西药分子的作用靶点结合的探讨。结果:我们利用软件构建了45个中药成分和3个强心类西药成分的平面结构和三维结构,通过分子结构相似度的比较和反向药效团搜索,发现这45个中药分子整体与洋地黄毒苷的相似度最高,同时中药分子中黄芪苷和人参皂苷与各西药分子的结构相似度最高;理化性质对比分析显示,3个强心西药的相对分子质量并不是最大的,然而其表面极性却最大;通过反向药效团搜索发现,这48个小分子中有10个小分子与66个蛋白药效团模型发生了较好的结合,其中西药地高辛只与一个药效团发生接合,而中药有6个成分都与多个药效团发生结合,其中以丹酚酸A结合的药效团最多。结论:与西药仅结合单一蛋白药效团不同,中药分子更易与多个蛋白药效团发生结合,由此推测其作用靶点和作用途径可能更为多样化。     

基于《中国药典》中药片剂质量控制项目变化趋势分析

基于《中国药典》2015年版与2020年版,系统性分析比较2版《中国药典》收载的中药片剂质量控制项目的相关内容,详细梳理性状、鉴别、检查项、含量测定、浸出物检测、特征图谱与指纹图谱等中药片剂的质量控制项目的差异。在2015年版的基础上,2020年版中对多项质量控制项目进行了完善和细节补充,提升了《中国药典》的科学性、规范性、权威性和实用性。同时针对目前《中国药典》在中药片剂质量控制项目方面的不足,对中药片剂的未来发展和质量管理提出了具体的思考和建议,为提高中药片剂的质量控制水平提供重要参考,也为新版《中国药典》中药片剂的编写和修订提供科学依据。     

Perspective of chemical fingerprinting of Chinese herbs

The holistic system of traditional Chinese medicine (TCM) is an integrity of the ingredients contained in the Chinese herbal medicines, which creates a challenge in establishing quality control standards for raw materials and the standardization of finished herbal drugs because no single component is contributing to the total efficacy. Chromatographic fingerprinting analysis represents a rational approach for the quality assessment of TCM. It utilizes chromatographic techniques, which include CE, GC, HPLC, HPTLC, etc., to construct specific patterns for recognition of multiple compounds in TCMs. Thus, chromatographic fingerprinting analysis of herbal medicines represents a comprehensive qualitative approach for the purpose of species authentication, evaluation of quality, and ensuring the consistency and stability of herbal drugs and their related products. The pragmatic comprehensive chromatographic fingerprinting analysis can disclose the detectable ingredients composition and concentration distribution under quantifiable operational conditions and therefore provide real-time quality information. It may leave a "gray" entity at the primary stage. However, consecutive study will deepen the knowledge and reduce its "gray scale", increase the transparency gradually, thereby strengthening its quality assessment potency.     

对EMA草药质量标准指南（第3修订版草案）的思考

草药及其产品的质量标准具有区别于化学药品或生物制品的特殊性，因此欧洲药品管理局（EMA）于2018年发布了“质量标准指南：草药物质、草药制剂和草药产品或传统草药产品的检验程序和可接受标准（第3修订版草案）”。EMA的草药及其产品的情况与我国中药有相似之处，从起始物料到成品多为活性成分未知的复杂混合物。目前我国尚未制定关于中药或中药材（饮片）质量标准相关指导原则。介绍该指南文件的主要内容，并结合中药质量监管情况进行分析，以期EMA相关质量标准制定的指导思路为制定中药质量标准提供参考。     

齐墩果酸含量测定的研究进展

齐墩果酸是多种中药的有效成分之一,具有多方面的重要生物活性,许多中药及其制剂均选用齐墩果酸的含量作为其质量控制的指标,本文对齐墩果酸含量测定方法的研究进展作一综述。随着含齐墩果酸中药的指纹图谱和质量标准方面研究的不断发展,简便快速、准确高效的测定方法也将会不断涌现,齐墩果酸的分离和含量测定技术将会日臻完善,为制剂中齐墩果酸的质量控制提供更可靠的依据。     

Harnessing traditional Chinese medicine to improve cancer therapy: issues for future development

Traditional Chinese medicine (TCM) has recently yielded a number of chemical compounds with clinically significant anticancer activity. The theory of TCM formulas, however, unlike Western medicine, is based on the interactions of the various Chinese medicinal materials in the body, rather than the activity of a single purified chemical compound. Mechanisms for the possible synergistic anticancer effects of components in TCM formulas have recently been postulated. Advanced research on the clinical effects of TCM formulas, however, has been hampered by inconsistent dosage formulations and unreliable quality control. Scientific challenges in dosage formulation and methods for ensuring quality control of TCM products will be discussed.     

中药指纹图谱与药效相关性研究进展

中药的疗效和安全性与其质量密切相关,研究中药成分与药效的关系,阐明物质基础,建立反映其内在品质的质量标准,是推动中药发展的关键所在。本文就近年来谱效关系中多维指纹图谱,药效学研究和数据处理技术等方面的研究进行总结,为中药谱效学的后续研究提供的参考。     

一测多评法研究进展

中药现代化对中药标准研究和质量控制提出了更高要求.一测多评法是通过采用一种内参物检测多种成分的方法,由于该法具有节约、准确等特性,得到了推广和应用.该文对近年一测多评理论与应用的研究进展进行探讨,可为中药质量控制提供参考.     

中药传统鉴定技术在医院中药饮片质量控制中的传承与应用

医院中药饮片的质量直接关系到患者的用药安全和临床疗效。通过参加全国中药特色技术传承人才培训项目,将所学中药传统鉴定技术在工作中加以传承与应用,建立医院中药饮片质量管理组织、实行中药饮片三级验收制度、培养中药传统鉴定技术人才等,从而确保中医临床疗效,保障临床用药安全,在医院中药饮片质量控制中发挥了重要的作用。     

医疗机构中药制剂质量标准处方中用药名称存在的问题探析

目的：为保证医疗机构中药制剂的质量、疗效和使用安全,探析医疗机构中药制剂处方中用药名称存在的问题、产生的原因、提出规范修订的建议及对策,旨在科学、规范医疗机构中药制剂质量标准处方中欠妥的用药名称。方法：考证分析云南中医集团调剂使用的中药制剂品种的质量标准处方中不科学、不规范的中药饮片名称和实际所指的中药饮片的品种和制品。结果：具有时代印迹的医疗机构中药制剂质量标准处方虽经过多次再注册和修订,但处方中的用药名称并未随着《中国药典》及地方标准的改版而及时修订,存在药物名称与实际用药和现行国家和地方标准不相符的情况。结论：因处方中药名称的问题,使得制剂生产面临着为保质量、疗效和使用安全而违规生产,或者放弃制剂的质量、疗效和使用安全的困境。本研究为确保中药制剂持续发挥疾病预防控制、中医特色服务的作用和优势,并为上级主管部门制定统一的标准提供依据和参考。     

Traditional Chinese medicine in COVID-19

COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across the globe, posing an enormous threat to public health and safety. Traditional Chinese medicine (TCM), in combination with Western medicine (WM), has made important and lasting contributions in the battle against COVID-19. In this review, updated clinical effects and potential mechanisms of TCM, presented in newly recognized three distinct phases of the disease, are summarized and discussed. By integrating the available clinical and preclinical evidence, the efficacies and underlying mechanisms of TCM on COVID-19, including the highly recommended three Chinese patent medicines and three Chinese medicine formulas, are described in a panorama. We hope that this comprehensive review not only provides a reference for health care professionals and the public to recognize the significant contributions of TCM for COVID-19, but also serves as an evidence-based in-depth summary and analysis to facilitate understanding the true scientific value of TCM.     

中药及其组分配伍的整合作用研究实践与进展

中药现代化研究的重要任务之一即明确中药(方剂)复杂药效物质基础及其配伍机制,但几十年来大部分中药的确切机制仍没有被阐明。原因一,中药的靶点不是西方人所理解的病的靶点,而是证的靶点。证强调疾病表型之间的关联,故中药的靶点是联系的靶点,组合的靶点;原因二,中药药效的物质基础不是一种有效单体,而是多种成分的有效组方。方是在证的基础上进行合理配伍和加减而建立的,是有规律和规则的,相应的中药不是孤立地作用于病的靶点而是系统地作用于证的靶点。西医有可以治疗该疾病相应靶点的药物,那么中医就有该证相应组合靶点的复方。目前认为,中药配伍的意义在于通过由特定活性物质群介导的多靶点、多途径整合作用发挥方证对应的终末效应。同时将中药配伍筛选为有效组分配伍,利用有效组分配伍阐明中药整合作用已成为近年来的普遍研究模式。而在传统的实验药理上,融合数学、生物信息学等多学科的定量药理学、逆向药理学、多向药理或网络药理学有助于理解中医药在治疗复杂性疾病中体现的整体性、系统性特点。     

中药配方颗粒临床应用医学理论商榷

目的探讨中药配方颗粒临床应用的科学性。方法通过对中药传统理论分析和药品管理法律法规的论述,对中药配方颗粒临床应用的科学性、产品质量的合法性进行讨论。结果中药配方颗粒临床应用缺乏医学理论依据,质量保证措施粗犷,合法性有待于进一步确认。结论目前,中药配方颗粒在临床大量推广应用的时机尚未成熟,临床应用医学理论有待商榷。     

中医儿科临床辨病与辨证结合探析

中医儿科临床应用现代诊断手段,拓展传统中医四诊,将西医辨病与中医辨证相结合,有助于理解中医证候,全面了解疾病和判断预后,具有优化治疗方案的优势,还可开拓中医科研思维,同时指出对诊断不明确、疗效不确切的疾病适宜中医辨证论治。旨在将中医辨证与西医辨病相结合,如何取长补短,让患儿获得更好的疗效,是今后努力的方向。