Classical famous prescriptions refer to the prescriptions recorded in the medical books of the Qing Dynasty and before the Qing Dynasty, which are still widely used, have definite clinical effects, and have obvious characteristics and advantages. From the description of the supplementary provisions on the registration and administration of traditional Chinese medicine in 2008 to the implementation of the law of the people's Republic of China on traditional Chinese medicine in 2017, to the issuance of the catalogue of ancient classical famous prescriptions (the first batch) (hereinafter referred to as the catalogue) and the administrative provisions on the examination and approval of simplified registration of traditional Chinese medicine compound preparations of ancient classical famous prescriptions (hereinafter referred to as the administrative provisions) in 2018. After 10 years of cultivation and improvement, the relevant policies of classic famous parties have finally formed a relatively supporting policy system. In addition, it also profoundly shows that the national level has carefully considered, attached great importance to and strongly supported classic famous parties. However, despite the favorable policy environment, there are still many difficulties in the research and development of classic famous parties. How the research and development of classical famous prescriptions can stand out from the traditional Chinese medicine varieties with about 60000 drug approval numbers is affected by many factors, such as the determination of the medicinal material base, the dose of the medicinal flavor, the development of the material benchmark of classical famous prescriptions, etc., which lead to the slow pace of the research and development of classical famous prescriptions, and even get into trouble. Based on CNKI database, this paper refines the research and development suggestions or inspirations of classical famous prescriptions, sorts out and analyzes the contents of the suggestions or inspirations in the literature, synthesizes the opinions of various schools, absorbs the opinions of various schools, constructs the research and development outline of classical famous prescriptions, discusses several key issues in the research and development of classical famous prescriptions, such as literature research, high-quality medicinal materials / decoction pieces, material benchmark, high-quality and preferential policies, and provides references for the research and development of classical famous prescriptions, so as to better and faster promote the industrial development of classical famous prescriptions and serve human health.

1. Method

CNKI is taken as the data source and advanced retrieval method is adopted. The retrieval conditions are that the publication time is from January 1, 2008 to September 10, 2018, the subject = classic name square and the title = classic name square (exact match), and cross database retrieval. A total of 112 documents were obtained. Each document was read and analyzed, and articles related to R & D suggestions or inspirations of classic famous prescriptions were extracted.

2. Results and analysis

A total of 14 literatures mainly involve the suggestions or enlightenment of classical famous prescriptions. See Table 1 for the summary of relevant contents. The catalogue and the management regulations are the cornerstone of the research and development of classic famous parties. According to the time when the catalogue was issued, 14 documents were classified. When the catalogue and the management regulations were not issued, the predictive suggestions and discussions of relevant scholars on classic famous parties were called early suggestions; Literature is the suggestions and Enlightenment Given by relevant personnel to the research and development of classic famous parties according to the catalogue and management regulations, which is called late suggestions. The early suggestions laid a good foundation for the research and development of classic famous prescriptions, and the later suggestions provided a useful reference for ensuring the vitality of classic famous prescriptions. Both emphasized that quality is the essence of classic famous prescriptions, and high quality is the basic feature of classic famous prescriptions.

Table 1 Summary of suggestions or inspirations in the literature related to the research and development of classic famous prescriptions




2.1 early suggestions laid a good foundation for the research and development of classic famous parties

      The pre proposal covers the whole industry chain process of classic famous prescriptions, medicinal materials / decoction pieces, intermediates, finished products and so on, as well as clinical positioning, supervision, intellectual property protection and so on. Among them, prescription selection and prescription dosage are the most talked about issues, and there are four papers dealing with such issues. At the same time, the view that the toxic drug flavor can be developed is put forward. For the pending dosage problem, the importance of practice was emphasized. It was considered that the dosage problem of classical famous prescriptions should not be limited to the quality of decoction pieces, but should be comprehensively considered with the decocting process; The compatibility ratio of classical famous prescriptions should be consistent with the original prescriptions, and the dosage should be further confirmed by pharmacodynamics and safety on the basis of literature. In the 7 articles proposed in the early stage, the literature carefully and comprehensively discussed the whole process of research and development of classic famous prescriptions, including prescription selection, prescription dosage, source of medicinal materials, evaluation of production process consistency, and characterization of rdetp quality and potency. Corresponding countermeasures and suggestions are put forward for each content, and rdetp is proposed for the first time, which puts forward requirements for specific practices, quality and potency characterization research, points out the direction for the research and development of classical famous prescriptions, and lays a good foundation for the later development of the material benchmark of classical famous prescriptions and the production of preparations.

2.2 suggestions in the later stage provide a useful reference for ensuring the vitality of classic famous prescriptions

      In the later stage, the suggestions mainly focus on the quality of the finished products of classical famous prescriptions and the operation strategy after the products are put on the market, which provides a useful reference for the protection of the vitality of classical famous prescription compound preparations. The quality of the finished products of classic famous prescriptions is the most important, and it is discussed in every literature. In terms of quality, safety and curative effect, it is proposed to investigate the well-known pharmaceutical enterprises in Japan and learn from their mature experience in making standard decoction to ensure the quality of traditional Chinese medicine preparations; Attach importance to and strengthen the research on the quality of medicinal materials, fix the production process and conditions, establish the quality control requirements for medicinal materials, decoction pieces, intermediates and finished products, and strengthen the research on the uniformity and stability of product quality in the design and research of product quality; Pursue the concept of "fine management and process control" in quality control; The core idea of the road of industrial development is "inheriting classics with high-quality products and driving the market with value"; 4 key links of innovative development of classic famous parties and other high-quality development suggestions. The post marketing operation strategies of the products include allowing the classic famous prescription preparations to be used by western medicine, including them in medical insurance, paying attention to post marketing re evaluation, establishing the classic famous prescription expert committee, developing third-party testing, improving the registration and bidding system, adding modern and clear indications in the instructions, etc., so as to provide suggestions for the future quality improvement and market development of the classic famous prescription products, effectively ensure the vitality and vitality of the classic famous prescription products in the future market, and promote the healthy and sustainable development of the classic famous prescription business.

2.3 quality runs through the research and development of classic famous parties, and high quality is the basic feature of classic famous parties

Whether it is the pre proposal or the post proposal, the quality always runs through the whole process of the research and development of the classic famous party. There are suggestions on how to control the quality from the aspects of feeding, intermediates and finished products. Classic famous parties after listing should also pay attention to quality monitoring, such as re evaluation after listing, establishment of "trial sale period", adverse reaction monitoring and other measures. Therefore, the biggest difference between the classic famous prescription compound preparation and other Chinese patent medicines in the market is to give high-quality connotation. High quality is its basic feature and the foundation of its future market.

3. Construction of R & D profile of classic famous parties

Through the analysis and induction of the suggestions or inspirations in the relevant literature of classical famous prescriptions, the R & D outline of classical famous prescriptions can be clearly constructed. The research and development of classical famous prescriptions is mainly divided into three parts, namely, prescriptions, material benchmarks of classical famous prescriptions and products. See Figure 1.


Figure 1 Outline conception of classic famous party R & D

      For prescriptions, the main management method is the catalogue system. The State Administration of traditional Chinese medicine has announced the first batch of 100 famous classical prescriptions, and other famous classical prescriptions will be announced later. Therefore, the prescription selection is not difficult for enterprises or relevant R & D units, and there are ready-made prescriptions for reference. However, it is a question worthy of careful consideration as to which classic famous party to choose for R & D. The author believes that the first thing is to have a precise clinical positioning, and the second thing is to see whether the enterprise has the production qualifications and capabilities of medicinal materials, decoction pieces, intermediates and Chinese patent medicines. The selected medicinal materials should have the characteristics of clear base, standard planting and standard processing in the real estate area, so as to ensure good quality and sustainable supply of resources. The decoction pieces follow the standardized processing and processing, and the standard decoction pieces can directly form a prescription; For the prepared slices without standards, it is necessary to carry out a large number of studies to establish standards and file them with relevant departments, and then form a prescription.

        It is very important to study the material standard of classical prescriptions. Select different quality medicinal materials from at least 3 bases in the real estate area, and make corresponding decoction pieces according to the processing requirements and specifications of classic works. Then the decocting process was strictly in accordance with the ancient book preparation method, and more than 10 batches of classic famous prescriptions were made. In order to ensure the uniformity and stability of the material standard of classical famous prescriptions, the method of uniform batch mixing can be adopted for the medicinal materials with large quality differences. The characterization of the material base of classical famous prescriptions should include qualitative identification, multi-component quantitative analysis, index component transfer rate, extract yield, fingerprint and other indicators. If necessary, it is recommended to add bioassay for determination. Thus, the quality parameters of each index of the material standard of classical famous prescriptions are obtained, which is convenient for the quality evaluation of finished preparations.

      Product research includes fine process research (including technical parameters such as decoction piece specification, feeding method, temperature rise procedure, filtration, concentration and drying), product quality control and standard research as well as research on other aspects of later products (brand promotion, market re evaluation, adverse reaction monitoring, etc.), while process research, product quality control and standard research are evaluated against the standard quality range of classic famous substances, so as to ensure the stability and uniformity of product quality. At the same time, it pays attention to the innovative research of prescriptions, material benchmarks of classic famous prescriptions and various dimensions of products, always has the awareness of intellectual property protection, and actively applies for patents once there is innovation. In the whole research and development process of classic famous prescriptions, it is also necessary to establish a perfect quality tracking system of traditional Chinese medicine, track and supervise the key links such as planting, processing, circulation and use, practice the concept of "traceability from the ground to the bedside", strengthen the quality and safety management and risk prevention and control in the whole process, and ensure the drug safety of consumers.

4. Discussion on several key problems in the research and development of classic famous prescriptions

4.1 literature research is the premise for the research and development of classic famous prescriptions

The major bonus policy of "no clinic, no efficacy" of classic famous prescriptions is based on its long medicinal history. After thousands of years of clinical use of traditional Chinese medicine, it can ensure the clinical safety and effectiveness. This kind of clinical evidence is hidden in the vast literature, which is in urgent need of excavation and extraction. Although classical famous prescriptions can not be defined as new drugs, they still submit "overview materials" according to the requirements of the measures for the administration of drug registration on the registration of new drugs. Therefore, the collation, mining and research of classical famous prescriptions are extremely important, which is the premise of the research and development of classical famous prescriptions. At the same time, it also has the effect of "sharpening the knife without mistaking the firewood cutter". Because in the process of collating and analyzing a large number of literatures, it helps to clarify the clinical positioning and solve the problems in the aspects of basic principles, processing, dosage, etc., and promotes the smooth progress of the research and development of classic famous prescriptions, especially in the aspect of clinical positioning.

4.2 high quality medicinal materials / decoction pieces are the basis for the research and development of classic famous prescriptions

"Good medicinal materials are good medicines", emphasizing that raw medicinal materials are the key factors affecting the quality of traditional Chinese medicine products. The literature proves that the influence of raw materials on the quality of Chinese patent medicine is greater than that of technology. At present, the quality problems of traditional Chinese medicine and decoction pieces are not optimistic, such as blind cultivation, non authentic products as authentic products, illegal doping, weight gain and dyeing, excessive sulfur fumigation, nonstandard processing of decoction pieces, and various specifications. These are the key factors that affect the quality of traditional Chinese medicine preparations at this stage. Therefore, we should pay attention to the quality of the raw materials of classical famous prescriptions. Genuine medicinal materials are recognized through long-term clinical practice. Similarly, the medicinal materials planted according to the gap can also be used as high-quality medicinal materials. Therefore, the author suggests that the gap standardized medicinal materials in the real estate area should be the first raw materials for the research and development of classic famous prescriptions, and then processed into decoction pieces through standardized processing, so as to ensure the quality of the finished products of classic famous prescriptions. This requires that classic famous recipe manufacturers should have corresponding production bases for medicinal flavor, so as to ensure the internal quality of products; Second, we can conduct resource assessment to stabilize the continuous supply of medicinal materials and deal with market risks; Third, the traceability of raw materials and medicinal materials can be realized.

4.3 the research on the material benchmark of classical famous prescriptions is the core of the research and development of classical famous prescriptions

The Japanese standard decoction provides a good chemical and biological benchmark for Chinese preparations, plays an important role in the quality evaluation of Chinese preparations, and promotes the development of Chinese preparations industry. The material standard of classical famous prescriptions is similar to that of Chinese standard decoction and has reference function. It is the key to the success of the development of classic famous parties and the core of the development of classic famous parties. How to study the material standard of classical famous prescriptions has always been a hot topic for researchers. The author believes that the development of the material standard of classical famous prescriptions is mainly to solve the problems of extraction process and quality characterization. As for the extraction process, it is suggested that on the basis of complying with the preparation method of ancient books, the drug flavor, compatibility, decocting process, etc. should be defined, and they should be transformed into modern and accurate extraction process as far as possible, so as to ensure the uniformity and stability of the material standard of classical famous prescriptions and facilitate the evaluation of product quality. In terms of quality characterization, we can refer to the quality control and potency characterization items involved in the literature, so as to comprehensively control the material benchmark of classical famous prescriptions.

4.4 high quality is the guarantee of the vitality of classic famous brands

The proposal of the strategy of strengthening the country through quality has raised the requirements for product quality to a national level. Especially for drugs, quality is life, and high quality is the symbol of drug quality and efficacy. The research and development of classic famous prescriptions should highlight their high-quality characteristics. Only when the quality is guaranteed, the curative effect can be guaranteed. Just like the Chinese preparations in Japan, they focus on quality and occupy most of the international market of related drugs in a small volume. Through the characteristics of great clinical value, strong scientific value and high market value, Li Geng and others identified and screened 552 products (data as of 2017). Some of these products also originated from classic famous prescriptions, such as Liuwei Dihuang pills, Yupingfeng granules, Angong Niuhuang pills, etc. The research and development of classical famous prescriptions is by no means just a few more traditional Chinese medicine varieties in the general sense, but should pay more attention to their high-quality characteristics. Only in this way can we develop classic famous prescription products that meet the needs of clinical medication of traditional Chinese medicine, serve human health, win the market and create brands, so as to ensure the vitality of classic famous prescriptions and inherit and develop the cause of traditional Chinese medicine.

4.5 preferential policies are the driving force for the industrial upgrading of classic celebrities

Policy is one of the important factors affecting drug development and an important guarantee for industrial upgrading. The author believes that, as a new thing, even if the classic famous prescription compound preparation comes out, it may be in a weak position in the whole pharmaceutical environment without the support of relevant policies, and the industrial development is difficult to continue. Therefore, it is suggested that the relevant departments of the state should give preferential policies to the classic and famous prescription products, such as including them in the medical insurance, entering the national catalogue of essential drugs, and excluding the proportion of drugs, so as to expand the market scale of the classic and famous prescription products, promote industrial upgrading, and lay a foundation for the re evaluation after listing.

Article source:

Dengzhe, liudewen, Dujie, Zhang Qing, etc;
China traditional Chinese Medicine Co., Ltd., Institute of traditional Chinese medicine, Chinese Academy of traditional Chinese Medicine
Chinese Journal of experimental formulary November 22, 2018