A holistic strategy for quality and safety control of traditional Chinese medicines by the “iVarious” standard system

An effective quality control system is the key to ensuring the quality, safety and efficacy of traditional Chinese medicines(TCMs). However, the current quality standard research lacks top-level design and systematic design,mostly based on specific technologies or evaluation methods. To resolve the challenges and questions of quality control of TCMs, a brand-new quality standard system, named "iVarious", was proposed. The system comprises eight elements in a modular format. Meaning of every element was specifically illustrated via corresponding research instances. Furthermore, frankincense study was taken as an example for demonstrating standards and research process, based on the "i Various" system. This system highlighted a holistic strategy for effectiveness,security, integrity and systematization of quality and safety control standards of TCMs. The establishment of"i Various" integrates multi-disciplinary technologies and progressive methods, basis elements and key points of standard construction. The system provides a novel idea and technological demonstration for regulation establishment of TCMs quality standards.

Development of chromatographic technologies for the quality control of Traditional Chinese Medicine in the Chinese Pharmacopoeia

As an important branch of medicine, Traditional Chinese Medicine(TCM) has been applied for the treatment of diseases for thousands of years in China and other countries in East Asia. The Chinese Pharmacopoeia(ChP) is a drug code formulated by the Chinese government, and it includes a special volume for the monographs of TCM, which plays an important role in ensuring the quality of drugs. The use of quality control technology has always been a complex and important factor in TCM. Owing to the chemical diversity of TCM, chromatography technology has been proven to be a comprehensive strategy for the assessment of the overall quality of TCM and has become the main analytical method in the ChP.This article provides an overview of the classical and modern chromatographic technologies applied in the ChP, and summarizes the advantages and disadvantages of each technique in the TCM monographs.In 2020, the new edition of the Ch P(the 2020 edition) has been implemented at the end of 2020. This paper also contains a brief introduction about the application of chromatographic technologies in the new edition of the ChP.

Quality Markers of Traditional Chinese Medicine:Concept,Progress,and Perspective

As the most important complementary medication against a variety of diseases,traditional Chinese medicines(TCMs)have been extensively applied over thousands of years.Current quality control of herbal medicines,however,is in great dispute.Unlike chemical drugs,which have clear and validated quality standards,the content of only one(or a few)compounds of many herbs and preparations is currently assessed as an indicator of quality,even though the assessed compound(s)is neither closely associated with the efficacy nor representative of the medicine as a whole.Based on the clinical use,compatibility of multiple component prescriptions,and manufacturing process of TCM,the new concept of a TCM quality marker that was proposed in previous work is discussed further here.In addition,practical technological approaches are described for the qualitative analysis and quantification of TCMs including herbs,processed products,and preparations,which lead to the discovery and identification of specific chemicals as quality markers and new quality control patterns.The progress that has been made in TCM quality control is also addressed.This work provides useful information for the quality control of herbal medicines in the future.

Multimodal integrated strategy for the discovery and identification of quality markers in traditional Chinese medicine

With the modernization and internationalization of traditional Chinese medicine(TCM),the requirement for quality control has increased.The quality marker(Q-marker)is an important standard in this field and has been implemented with remarkable success in recent years.However,the establishment of Qmarkers remains fragmented and the process lacks systematicity,resulting in inconsistent quality control and insufficient correlation with clinical efficacy and safety of TCM.This review introduces four multimodal integrated approaches that contribute to the discovery of more comprehensive and accurate Qmarkers,thus aiding in the establishment of new quality control patterns based on the characteristics and principles of TCM.These include the whole-process quality control strategy,chemical-activity-based screening method,efficacy,safety,and consistent combination strategy,and TCM theory-guided approach.Furthermore,methodologies and representative examples of these strategies are described,and important future directions and questions in this field are also proposed.

Quality Control for Traditional Medicines–Chinese Crude Drugs

Distinguished guests,ladies and gentlemen,I am very happy to meet many of my old friends today.I would also like to thank Chinese Pharmaceutical Association for providing me with such a good opportunity to communicate with Chinese and European friends.The topic of my report today is the quality standard of Chinese crude drugs and the development ideas.Director Ma introduced the relevant situation of the quality standards of Chinese patent medicines.

Quality Control for Traditional Medicines–Chinese Patent Medicines

Ji Shen: Dr.Ma Shuangcheng,Director of Institutes for Control of Chinese Traditional Medicines and Ethnic Medicine,National Institutes for Food and Drug Control,is a long-term researcher on the quality standards of Chinese materia medica,Chairman Member of the Risk Assessment of the Pharmacopoeia of People's Republic of China ,and is also the Director Member of the Professional Committee of Drug Risk,China Pharmaceutical Association,and the Director Member of the Directors Committee of Chinese Materia Medica Quality and Safety.He has long been engaged in the control of the quality and safety of Chinese materia medica,and has also been included in the National 10000 Talent Plan.Let's invite Dr.Ma to give a report.Thank you.

Translational Chinese Medicine: A Way for Development of Traditional Chinese Medicine

Translational Chinese medicine is one of the latest developing fields in traditional Chinese medicine. In this paper, we discuss the “3 w” namely, “what is”, “why to advance”, “how to carry out” and the significance of translational Chinese medicine. To overcome the innate drawbacks of traditional Chinese medicine (TCM), the basic theory of TCM had better be refreshed. The safety and efficacy of classic formulae and therapy experience of TCM should be evaluated based on strict quality control and reaffirmed with evidence based medicine. The significance of translational Chinese medicine is to transform Chinese medicine into a balanced, personalized medicine with sound safety, good efficacy and strict quality control.

Deeper Chemical Perceptions for Better Traditional Chinese Medicine Standards

Traditional Chinese medicines (TCMs), a complex system of natural resources with many diverse components, are widely used as approved medicinal agents in China. Quality control of TCMs is a huge challenge for the government and for testing institutes and is associated with numerous scientific issues. Among these considerations include the following questions: How many components are in TCMs? How can the multiple components in TCMs be comprehensively delineated and subsequently characterized? What is the level and range of these (active) metabolites within these multiple-component TCMs, in order to recommend standards? and What are the qualities required for a marker constituent to be selected, and from a practical perspective, how can these components be assessed with low cost and in a short time? All of these factors require significant and deep thinking in order to understand the individualistic chemistry of TCM in order to develop enhanced TCM quality standards for improved and consistent patient care. In this review, the latest exploratory research in TCM chemistry analytical techniques and methods is summarized in order to begin to develop responses to these scientific issues. Advances in these methods have included multidimensional separation for liquid chromatography–high-resolution mass spectrometry (LC–HRMS), smart triggering data-dependent acquisition of LC–HRMS, target analysis with liquid chromatography–mass spectrometry (LC–MS), supercritical fluid chromatography, and data mining of large mass spectrometry (MS) datasets. In addition, two quality strategies have been introduced in order to save reference standards and the analysis time for a TCM quality standard, including the application of the single standard to determine multi-components (SSDMC) and monomethodheterotrait matrix methods. Finally, a series of future improvements for analytical methods for TCMs are proposed.

Carbon quantum dot preparation and application to detecting active ingredients in traditional Chinese medicine

Carbon quantum dots(CQDs)are fluorescent carbon nanomaterials that have been applied to biology,medicine,and optoelectronics,owing to their significant advantages such as simple synthesis methods,low cost,and widely available sources of raw synthesis materials.This review summarizes CQD preparation methods,which include hydrothermal and microwave-assisted synthesis methods,as well as separation methods such as centrifugation,dialysis,and filtration.Additionally,we review the application of CQDs in the detection of active ingredients,primarily phenolic compounds,in traditional Chinese medicine.We also discuss the quenching mechanism of CQD fluorescence using the active ingredients of traditional Chinese medicine.Limitations such as insufficient test selectivity,weak fluorescence intensity,and an unclear quantitative relationship between preparation methods and properties should be resolved for the efficient use of CQDs to detect active ingredients in Chinese medicine.

The Role of the European Pharmacopoeia(Ph Eur)in Quality Control of Traditional Chinese Herbal Medicine in European Member States

In order to assure the safety and efficacy of the Chinese Medicines in Europe, the quality of TCM herbals should be guaranteed so that they can be freely imported in the European Union and other Western European Countries which are signatories of the European Pharmacopoeia Convention. Consequently, new Ph Eur TCM herbal drug Monographs should be elaborated, based on preexisting Monographs in the Chinese Pharmacopoeia(Ch P) 2010.Such a program has been inaugurated in 2005 by the Ph Eur Groups of Experts 13 A and B(Phytochemistry). Since then good progress has been made, elaborating of about one third of the originally proposed 100 TCM herbals being identified as important monographs for the European Market. Taking into account the many challenges still laying ahead, the establishment of a specialized Working Party(WP) on TCM with specialists and experts from many EU Member States has been decided by the Ph Eur Commission in 2008 which is highly active ever since in the examination and elaboration of new TCM herbal drug monographs, primarily to assure the safety of the European patient and further to provide quality parameters extremely important for all registration and licensing procedures of the respective National Authorities all over Europe.This paper is a survey of results and difficulties obtained so far which has been encountered meanwhile in the elaboration process by the Ph Eur TCM WP of these monographs and will discuss these in detail. Moreover the role of Ph Eur TCM monographs in the European community is addressed.

Survey and Practice of Reporting Quality of Randomized Controlled Clinical Trials on Traditional Chinese Medicine

Evidence obtained from randomized controlled trials （RCTs） has been generally accepted as the gold standard in the evaluation of clinical effectiveness. Readers need to understand the trial design, implementation, results, analysis and interpretation, so as to fully Jnderstand the results of RCTs. Thus, the investigators of RCTs have to report these items in a complete, accurate and clear manner. Since 1998, we have conducted several evaluations on the reporting quality of RCTs published in Chinese journals on traditional Chinese medicine （TCM） and results have shown that there is an urgent need for higher quality RCTs on TCM.

QUALITY CONTROL OF TRADITIONAL CHINESE MEDICINES: INVESTIGATION ON CHEMICAL MARKERS

Traditional Chinese medicines(TCMs)have played an important role in the treatment of diseases for thousands of years.With the rise of the combination therapy for multi-gene diseases,TCMs attracted more attentions gradually.However,TCMs is a complex system which could contain tens,or even hundreds of compounds.Selection of chemical markers is thus a key to the

Individualized Traditional Chinese Medicine treatment vs antibiotics for recurrent urinary tract infections: a multicenter, randomized controlled study

OBJECTIVE: To systematically assess the effects of individualized Chinese medicines on recurrent urinary tract infections(rUTIs).METHODS: This study recruited 230 adult female patients in the remission phase of rUTIs from five hospitals in China. The patients were randomly allocated to two groups: an individualized Chinese medicine group(n = 114) and a control group(n = 116). Patients in the Chinese medicine group received individualized Chinese herbs, which were evaluated for syndrome differentiation.Patients in the control group received antibiotic treatment combined with a Chinese medicine placebo. The duration of treatment was three courses of four weeks each, with a three-month subsequent follow-up. UTI recurrence rate,Traditional Chinese Medicine(TCM) syndrome scores,36-item Short Form Survey(SF-36) score, and urine secretory immunoglobulin A(SIgA) were measured and analyzed before and after treatment in each group. RESULTS: Patients from the Chinese medicine group exhibited significant decreases in both short-and longterm UTI recurrence rates compared with the control group(P < 0.05). The changes in TCM syndrome scores between the Chinese medicine and control groups were significant(P < 0.05). The changes in the average SF-36 quality-of-life scores in the Chinese medicine group were also significantly higher than those in the control group after treatment(P < 0.05). The Chinese medicine group also demonstrated a significant increase in urine SIg A expression. CONCLUSION: Taken together, compared to the oftenused long-term antimicrobial prophylaxis during the remission stage of r UTIs, treating patients with an individualized Chinese medicine decoction by syndrome differentiation could effectively reduce the recurrence rate, improve the patients' TCM syndrome scores and quality of life, and enhance immunity, which in turn helps to prevent antibiotic resistance.

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 chemicalmarkers-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.

Application of near infrared spectroscopy to the analysis and fast quality assessment of traditional Chinese medicinal products

Near infrared spectroscopy(NIRS)has been widely applied in both qualitative and quantitative analysis.There is growing interest in its application to traditional Chinese medicine(TCM)and a review of recent developments in the field is timely.To present an overview of recent applications of NIRS to the identification,classification and analysis of TCM products,studies describing the application of NIRS to TCM products are classified into those involving qualitative and quantitative analysis.In addition,the application of NIRS to the detection of illegal additives and the rapid assessment of quality of TCMs by fast inspection are also described.This review covers over 100 studies emphasizing the application of NIRS in different fields.Furthermore,basic analytical principles and specific examples are used to illustrate the feasibility and effectiveness of NIRS in pattern identification.NIRS provides an effective and powerful tool for the qualitative and quantitative analysis of TCM products.

Overview of the quality standard research of traditional Chinese medicine

Traditional Chinese medicine(TCM)has been widely used for the prevention and treatment of various diseases for a long time in China.Due to its proven efficacy,wide applications,and low side effect,TCM has increasingly attracted worldwide attention.However,one of the biggest challenges facing the clinical practice of TCM is the uncontrollable quality.In this review,the progress of the development and the current status of quality standard as well as new quality control techniques introduced in Chinese Pharmacopoeia(2010 edition),such as liquid chromatography hyphenated mass spectrometry(LC-MS),fingerprint,quantitative analysis of multi-components by single-marker(QAMS),thin layer chromatography bio-autographic assay(TLC-BAA),and DNA molecular marker technique,are briefly overviewed.

中医药临床应用N-of-1试验报告质量评价的研究

【目的】参照中医药单病例随机对照研究(N-of-1)试验指南(TCM-CENT)中的条目,对中医药领域应用N-of-1的试验报告质量进行评估。【方法】检索中国知网(CNKI)、中国生物医学文献数据库(CBM)、中文期刊数据库(维普)、万方数据库(万方)、超星期刊、PubMed、Web of Science等主要中英文文献数据库中的中医药N-of-1试验报告。由两名研究人员筛选合格的文章,并独立提取数据。参照TCM-CENT条目对纳入的文献进行计分并评估其报告质量。【结果】共纳入24篇(中文20篇,英文4篇)中医药N-of-1试验报告,其中单一N-of-1试验3篇,系列N-of-1试验21篇。两名评审员评价的一致性较高,Kappa值平均值为93%,有27个条目判断一致,最低值为65%,对应第16和第21条条目。条目平均报告率为61%,其中报告率为100%的有9个,未进行报告的有4个。讨论部分平均报告率最高(92%),其他信息部分平均报告率最低(25%)。单篇的报告率平均值为62%。【结论】中医药临床应用N-of-1试验尚处于起步状态,发展缓慢,试验报告的总体质量一般,在随机方法设计、样本量估算、不良反应报告及分析、试验方案的注册等方面,有待进一步完善和提高。

Simultaneous quantification of eighteen constituents in traditional Chinese medicine XiaoShuanTongLuo by UPLCMS/ MS

XiaoShuanTongLuo （XSTL） is an important multi-herbal formula widely used as a traditional Chinese medicine （TCM）. In this paper, an ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometric method （UPLC-ESI-MS/MS） was developed for the simultaneous identification and quantification of 18 chemical constituents in the extract of XSTL. The analysis was performed in multiple-reaction monitoring （MRM） mode using positive and negative electrospray ionization （ESI）. A BEH C18 （2.1 mm× 100 mm, 1.7 μm） column with a gradient mobile phase of methanol-0.1% aqueous formic acid solution at a flow rate of 0.2 mL/min was used for separation. The standard curves of most components showed good linearity over the concentration range of 0.001-0.5 μg/mL with r = 0.9896-0.9996. The relative standard deviations （RSD） of intra-day and inter-day precision were all lower than 15% at low, middle, and high concentration levels. The RSD of stability analysis in 24 h were also lower than 15%. The validated method was employed to quantify 18 active components simultaneously in four different commercial brands of XSTL products in various dosage forms. The developed method was rapid, accurate, sensitive, and reproducible for the quality control of XSTL.

公立中医医院绩效考核下中医病案首页全流程智能质控

随着公立中医医院绩效考核的不断推进,病案首页质量受到越来越多医院的重视,本研究探讨了采用信息化技术进行病案首页数据质控的效果,从中医病案首页全流程智能质控系统构建(事前质控、事中质控、事后质控)、应用效果两个方面陈述了病案首页数据全流程智能质控的流程,并通过数据体现了中医病案首页全流程智能质控系统可有效提高公立中医医院病案首页数据质量,为公立中医医院绩效考核、医院精细化管理提供数据支撑。