"The secret of traditional Chinese medicine is not the amount of medicine." Scientifically elucidating the dose-effect relationship and its influencing factors of formulas and systematically researching, summarizing and refining prescription dose theory have important implications for guiding clinical rational dose selection, safe and effective drug use, and improving clinical efficacy of TCM.

□ This reporter Pan Feng's key factors affect the efficacy of Chinese medicine in addition to syndrome differentiation and treatment, prescription compatibility, Chinese medicine properties and medicinal quality, and the dosage of prescriptions have a close relationship, the efficacy of the problem has become one of the outstanding bottlenecks restricting the further development of Chinese medicine. Experts attending the 382th Xiangshan Science Conference with the theme of “Seminar on Quantitative Effects of Formulations and Effects” held in Beijing earlier this year pointed out that the study on the dose-effect relationship of herbal medicines and the release of doses of this traditional Chinese medicine will not promote the secret of Chinese medicine and will promote Chinese medicine. Entering the quantitative era is an important way to improve the clinical efficacy of Chinese medicine.

For the purpose of improving efficacy, within a certain dose range, the relationship between the amount of drug and the effect is called the dose-effect relationship. Among them, the amount is the dose or blood concentration of the drug; the effect is the effect produced by the action of the drug. The purpose of the dose-effect relationship study is to elucidate the laws of drug action and provide important evidence for the development of new drugs, evaluation of dosage forms, and clinical drug use. From the dose-effect relationship, important parameters such as the minimum effective amount can be obtained. Because the chemical composition of chemical drugs is clear and the structure is clear, the concept, principle, method and application of the dose-effect relationship for single-component indicators have formed a relatively complete system. However, for traditional Chinese medicines with unclear effect components, the study of their dose-effect relationships is a new challenge.

The Executive Chairman of the conference and Prof. Tong Xiaolin from Guang'anmen Hospital of China Academy of Chinese Medical Sciences gave a report on the theme of the key questions and strategies for the study of dose-effect relationship of herbal medicine. Tong Xiaolin stated that Chinese medicine clinic is a dialectical thinking process with medicine, prescription, and quantity. Since ancient times, “Chinese medicine has not passed the secret in the amount of medicine”, and the amount of prescription is directly related to the clinical efficacy of traditional Chinese medicine. However, the original source dose of the lost prescription and the overly conservative dose threshold of traditional Chinese medicine, the unstructured prescription dose theory has affected the clinical efficacy to a certain extent.

Since the development of TCM for thousands of years, ancient and modern medical scientists have gained a lot of understanding about the dose-effect relationship of the other drug in long-term clinical practice and scientific research. Their understanding also has a certain depth. These understandings are scattered among various books. In addition, there are many understandings that have not been written. The research on the dose-effect relationship of prescription drugs is still lacking in mature models. Inheritance can no longer fully satisfy the needs of contemporary prescription dose-effect relationship research. "Clinical and therapeutic efficacy, inheritance and innovation are the key issues in the study of the dose-effect relationship of herbal medicine. The curative effect is the lifeblood of traditional Chinese medicine, and improving the clinical efficacy is the fundamental purpose of the study of dose-effect relationship of prescription medicine." said Tonglin.

The compound dose-effect relationship is more complex. The experts pointed out that the clinical practice of TCM is based on the principles of syndrome differentiation and treatment. It analyzes the clinical data collected by the four clinics, establishes the principle of treatment, and selects parties to use drugs. Its clinical efficacy mainly refers to the effect of the selected prescription acting on the human body. The factors that determine the efficacy of the selected formula are not only the drugs included, but also have a close relationship with the dose of the drug. Different from the concept of traditional pharmacological dose-effect relationship, the dose-effect relationship of traditional Chinese medicine compound is more complex and has more influencing factors. The dose-effect relationship should be explored through clinical research.

The role of traditional Chinese medicine prescription has typical characteristics of integrity. On the one hand, the medicine used in the intervention is a multi-component and orderly integrated system. That is, the “quantity” of prescription is different from the amount of a certain pharmaceutical composition of western medicine, but the entire prescription is traditional Chinese medicine. The amount of effective ingredients. On the other hand, the target is a whole person, that is, the “effect” of a prescription is not a change of a single target or a single efficacy index, but a multiple target or even multiple systems on the basis of a TCM syndrome. Function network. Therefore, the research on the dose-effect relationship of the prescription should be based on the combination of prescription and syndrome, and pay more attention to the study of overall characterization.

Experts at the meeting discussed that the difficulties that need to be overcome in the study of the dose-effect relationship of complex prescriptions include: the choice of clinical research objects and how to ensure the consistency of dose safety and effectiveness. In terms of clinical trials, it is difficult to establish more dose groups because of the long cycle, high cost, and ethical issues, and the dose-effect relationship of prescriptions is fully and systematically demonstrated. Therefore, sample size and experimental design methods are difficult to study; On the other hand, how to find a pharmaceutical research method that meets the characteristics of traditional Chinese medicine is a problem that can not be ignored in the study of the dose-effect relationship of herbal medicine. The treatment of Chinese medicine is focused on physical, legal, prescription, medicine, and quantity. The clinical research directly reflects the dose-effect relationship of prescriptions in practical applications. It is the best and final method for evaluating the rationality of Chinese herbal medicine dosages. It is a difficult point to study the efficacy evaluation system that can be recognized by Western medicine practitioners with reference to the methods of syndrome-infected medicine.

The research methods of complex research on compound dose-effect relationships for innovative research methods require new research ideas and research methods. The characteristics of TCM syndrome differentiation and treatment should be reflected under the guidance of TCM theory. Some experts suggest that qualitative methodological studies of the dose-effect relationship of prescription drugs will divide the study into two phases: the study of the dose-effect relationship between the prescription and the Junyao drug in the primary phase, and the efficacy of the compatibility of different doses of the compound drug in the advanced phase, and different choices in different study phases. Clinical research methods. The dose-effect relationship study of prescription drugs can start from single drug, unilateral and single disease, and the dose-effect relationship between drug pairs, small compound and proprietary Chinese medicines can gradually progress to the study of compound compounds with more taste; the selected disease species should be single and variable. Less, easy-to-observe therapeutic effects, objective efficacy indicators, repeatable measurements, and quantifiable.

Some experts proposed the use of "network target" ideas and methods of dose-effect relationship between prescription drugs, that is, through the quantification of the interaction, the other side of the agent's disease, card effect, side effects and other measures. Or start with the supramolecular structure of the compound decoction and explore the dose-effect relationship of prescriptions. The research methods of "study" and Chinese medicine coincide with the concepts and methodology of Chinese medicine. System biology may provide an opportunity for the study of modernization of traditional Chinese medicine. Experts at the conference emphasized the importance of translational medical research in the study of the dose-effect relationship of innovative prescription drugs, and pointed out that the implementation of translational medical research is very important to improve the efficiency of research and development. The application of modern evaluation methods will help to increase the speed and efficiency of research and development of new traditional Chinese medicines.

Experts participating in the meeting reached the following consensus on the research strategy of prescription drug dose-effect relationship.

The study of dose-effect relationship of herbal medicine should be based on clinical research, with the main objective of improving clinical efficacy, and taking the prescriptions of less drug, more precise and more effective macros as the starting point, as a model prescription for dose-effect relationship research, accelerating the succession of innovations. The pace of modernization of Chinese medicine. In the study of dose-effect relationships, the unity of safety and effectiveness is followed, the best effective dose in the safe range is explored, and the “batch of size and dosage” strategy is advocated to explore the best curative effect.

Applying the advantages from the clinic, the translational medicine model was adopted to transform the research results of the dose-effect relationship of prescription drugs into the clinic, and to improve the application value of the dose-effect relationship study of herbal medicine. We pay attention to the combination of multi-discipline, multiple methods and technical means, and integrate multidisciplinary research forces such as medicine, pharmacy, system biology, evidence-based medicine and statistics. Efficacy evaluation should be guided by traditional Chinese medicine theory to strengthen the quantifiable, objective, and digital research of TCM syndrome evaluation. At the same time, it should also absorb Western medical diagnostic indicators and new characterization methods in life sciences, and evaluate TCM syndrome evaluation indicators. New evaluation indicators such as evaluation indicators and systems biology are integrated into a comprehensive evaluation system.

Wang Guoqiang, Deputy Minister of Health and Director of the State Administration of Traditional Chinese Medicine pointed out at the National TCM Working Conference held in 2011 that the “12th Five-Year Plan” period is a crucial period for the comprehensive and coordinated development of Chinese medicine. It is necessary to strive for the scientific connotation of Chinese medicine. There have been new breakthroughs in interpretation, theories and technological innovation of traditional Chinese medicine, methodologies suitable for the development of Chinese medicine, and the construction of standards and standards systems.