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.

Protection and Quality Control of Wild Chinese Herbal Medicine Resources in Nature Reserves by Taking Longyuwan Scenic Spot Within Funiu Mountain Nature Reserve as an Example

This paper discussed how to protect and control the quality of wild Chinese herbal medicine resources in nature reserves by taking Longyuwan National Forest Park within Funiu Mountain Nature Reserve as an example. Through the combination of three methods including literature review, visiting and investigational studies, and field surveys, the data of investigation, collection and collation were analyzed. According to data of surveys, collection and collation, problems related to the protection of wild Chinese herbal medicine resources faced by Longyuwan Scenic Spot within Funiu Mountain Nature Reserve were also analyzed and protection strategies and quality control of wild Chinese herbal medicine resources in this nature reserve were discussed. It was expected that the results would provide important scientific references for the sustainable development, protection and quality control of wild Chinese herbal medicine resources within nature reserves.

Metabonomics/metabolomics analysis technology and its application in quality control of traditional Chinese medicines

Chinese medicines are an important part of traditional Chinese medicines,but their'safe,effective,stable and controllable'issue still remains to be solved.The rise of metabonomics in 20th century,consistent with the overall adjustment concept of multi-component,multi-level,multi-target,multi-metabolic pathways of traditional Chinese medicines,is conducive to solve basic problems in their quality control.This paper systematically describes recent application and development of 1H-NMR metabonomics techniques,LC-MS metabonomics techniques and GC-MS metabonomics techniques in the quality control of traditional Chinese medicines.It provides a new reference for Chinese medicines and the identification and quality assessment of their products.

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.

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 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.

Use of Chinese Herbal Medicine as an Adjuvant for Cancer Treatment: A Randomized Controlled Dose-Finding Clinical Trial on Lung Cancer Patients

Background: Cancer has become a leading cause of death world-wide. In Hong Kong, cancer accounted for 24.8% of deaths in 1980, rising to 31.3% in 1998. The conventional treatment of cancer usually includes surgery, radiotherapy and chemotherapy. These conventional therapies do not guarantee not relapse and are often associated with serious side effects. Using Chinese Medicine (CM) as an adjunctive treatment is commonly practiced in Chinese Communities to support patients being treated with conventional modern medicine, with the aim of alleviating the side effects, and improving self-defense and their quality of life. Well-designed and conducted clinical trials could give evidence of the efficacy of CM. This study investigated the clinical efficacy through the well designed clinical trial, and the implementation of carrying out the trial, to assess the adjuvant and supportive effect on lung cancer patients. Methods: The clinical study was designed as a randomized controlled trial to investigate the dose-dependent effects. Primary endpoint was the difference of Functional Assessment of Cancer Therapy-General (FACT-G) score. Results: 41 eligible subjects were enrolled and randomly divided into 2 groups, 21 in high dose group and 20 in low dose group. Sub-domains of PWB (Physical well-being) and EWB (Emotional well-being) as well as FACT-G total score were significantly improved in high dose group when compared with low dose group after 12 weeks treatment (p = 0.015, 0.006 and 0.012, respectively). Conclusions: Holistic approach using quality of life as parameters to evaluate the efficacy of CM is an important compromise. Well-designed clinical trial can provide convincing evidence to support CM’s efficacy. The study demonstrated that quality of life of patients with lung cancer could be beneficial from the supportive care with CM.

Considerations on the Quality Standards Reflecting the Characteristics of Compound Preparations of Traditional Chinese Medicine

Objective To study the current quality standard of traditional Chinese medicine(TCM)and its limitations in China,and encourage enterprises to take more responsibility to promote the development of this industry.Methods Based on the analysis of the status quo and problems of the quality standard system of TCM,the quality control mode,as well as the problems found in the reevaluation after marketing,some suggestions were put forward for adjusting the current quality standard of TCM.Results and Conclusion Through strengthening the quality control of the source,and under the premise of ensuring the safety,effectiveness and stability of TCM,the quality standards of TCM can be improved greatly.

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.

The Prospect of Application of Extractive Reference Substance of Chinese Herbal Medicines

The emerging development of Extractive Reference Substance (ERS) is a methodology that meets the needs for quality control for Chinese Herbal Medicines (CHM) and respects the holistic viewpoint of Traditional Chinese Medicine (TCM) and its clinical use of multiple ingredients with synergistic effects. The convention of using just a selected few Chemical Reference Substances (CRS) cannot adequately assess the quality of intact CHM. A validated chemical spectrum of an ERS provides the global characteristics in order to more specifically identify and assess targeted CHM. This paper describes the fundamental concepts, potential significance, and basic criteria of ERS, along with methods of preparation and calibration. Given the diversity of CHM, the various problems that will occur in establishing the proper process of ERS will need to be solved in a step by step manner. The ERSs of Ziziphi spinosae semen and ERS of Fritillaria thunbergii bulbus are given as examples of the development of ERS and demonstrate why we are optimistic about the utility of this approach.

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.

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.

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.

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.

Gain deeper insights into traditional Chinese medicines using multidimensional chromatography combined with chemometric approaches

Traditional Chinese medicines(TCMs)possess a rich historical background,unique theoretical framework,remarkable therapeutic efficacy,and abundant resources.However,the modernization and internationalization of TCMs have faced significant obstacles due to their diverse ingredients and unknown mechanisms.To gain deeper insights into the phytochemicals and ensure the quality control of TCMs,there is an urgent need to enhance analytical techniques.Currently,two-dimensional(2D)chromatography,which incorporates two independent separation mechanisms,demonstrates superior separation capabilities compared to the traditional one-dimensional(1D)separation system when analyzing TCMs samples.Over the past decade,new techniques have been continuously developed to gain actionable insights from complex samples.This review presents the recent advancements in the application of multidimensional chromatography for the quality evaluation of TCMs,encompassing 2D-gas chromatography(GC),2D-liquid chromatography(LC),as well as emerging three-dimensional(3D)-GC,3D-LC,and their associated data-processing approaches.These studies highlight the promising potential of multidimensional chromatographic separation for future phytochemical analysis.Nevertheless,the increased separation capability has resulted in higher-order data sets and greater demands for data-processing tools.Considering that multidimensional chromatography is still a relatively nascent research field,further hardware enhancements and the implementation of chemometric methods are necessary to foster its robust development.

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

MHC-2D LC STRATEGY FOR THE HOLISTIC QUALITY CONTROL OF NOTOGINSENG-CONTAINING CHINESE PATENT MEDICINES

Current China Pharmacopoeia(ChP)standards employ diversified and case-dependent assay methods to evaluate the quality of different Chinese patent medicines(CPM)that contain Panax notoginseng as the monarch drug.These conventional HPLC-based approaches utilizing complex sample preparation procedure can easily result in low analytical efficiency and possible component loss.We thereby propose a'monomethodheterotrait matrix'(MHM)