ABSTRACT
Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.
Subject(s)
China , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Prescriptions , Public HealthABSTRACT
The development of traditional Chinese medicine(TCM) has always been highly valued and supported since 1949. However, Chinese medicine industry still faces great challenges in view of the current status of the industry and registration and approval of new products in recent years. Related policies also directly influence the development of the industry. The latest version of the Provisions for Drug Registration and Requirement on Registration Classification and Application Information of Traditional Chinese Medicines have been put into practice since 2020. Registration classification is the core content of the Chinese medicine registration management system, as it is closely related to the research, development, and registration of Chinese medicine and the innovative development of the industry. This article aims to systematically review the historical evolution of the category of Chinese medicine registration and analyze the current status and problems, which is expected to provide a reference for the formulation of supporting documents according to related laws and regulations.
Subject(s)
Drug Industry , Drugs, Chinese Herbal , Medicine, Chinese Traditional , PolicyABSTRACT
To review the research progress of anticancer realgar preparations from the perspective of patent，in order to provide a reference for the research of new antitumor realgar drugs. IncoPat database was retrieved with keywords plus IPC classification number. Original data and 72 patents of anti-cancer realgar preparations were obtained and included after artificial denoising. The quantitative analysis was made on the information about application trends，application types and patentee. The technical points of representative patents were summarized. ① The patent types of anticancer realgar preparations are mainly product patents. Its technological innovation has undergone the development of realgar compound agents，arsenic sulfide single agents，nanometer products of realgar agents，bioleaching of realgar preparations，compound realgar extract preparations，compound nano realgar preparations and arsenic sulfide polymorphic crystalline structure. ② Nano realgar agents， realgar bioleaching preparations， new crystalline type realgar preparations and realgar compound preparations. ③ The following studies should be strengthened in the future，involving the comparison of biological effects and toxicity of nano realgar preparations of different preparation processes，the selection of optimal particle size，the druggability of realgar bioleaching preparations，the discovery of new As4S4 crystalline forms and the secondary development of anticancer realgar preparations.
ABSTRACT
The European Union (EU) law 2004/24/EC has simplified the registration of traditional herbal medicines, which makes it possible for Chinese materia medica (CMM) to enter the EU as medicines. To register CMM products in the EU is an important way to realize the internationalization of CMM. Compound combination is the main clinical application form of CMM under the guidance of CMM syndrome differentiation. How to register compound CMM products in EU has become one of the important realistic topics for the internationalization of CMM. A total of 630 applications for traditional herbal medicinal products have been approved by the EU member states since the implementation of the Directive 2004/24/EC in 2005. Among these products, Padma Circosan Capsules was the only approved one originated from CMM area. The course of this product lead us with the enlightenment for the compound CMM products in three aspects: The literatures and evidence about safety and traditional use of "related product" are the core components in the non-clinical and clinical application materials for the registration of both combination and mono-component CMM products; The traditional application and safety evidence of "related products" as well as the relevant materials and data of EU monograph constitute the important content for the registration and approval of compound CMM products in EU member states; Applicants should pay more attention to the study of genotoxicity and the systematic collection of post-marketing pharmacovigilance data.
ABSTRACT
The Community Herbal Monograph (CHM) is an official document which reflects the scientific opinion of European Medicines Agency (EMA) and plays an important role in technical harmonization of the herbal medicinal products. The role of CHM is very similar with the centralized procedure in the EU level as it represents the technical coordination results of the assessment about safety and efficacy of herbal medicine. The monograph and national procedure, decentralized procedure, and mutual recognition procedure together constitute the coexistence characteristic of centralization and decentralization of the EU medical legislation. The CHM and the traditional herbal medicine registration also constitute the core content of Directive 2004/24/EC in the EU and member state level respectively. And the CHM plays an important role in the registration of traditional herbal medicinal products in the EU member state. However, it has not yet been fully studied by domestic experts and scholars. This paper makes intensive studies on the value of CHM and analyzes the application of monograph in traditional herbal medicine registration. The purpose is to clarify the value and importance of CHM in the registration of traditional Chinese medicine in EU and to provide reference for the Chinese enterprises which are aspiring to open up the EU market.
ABSTRACT
Registration of Chinese patent medicine in European Union (EU) is of great significance to the internationalization of traditional Chinese medicine as EU market acts as an important position in the global botanical market. In retrospect, the domestic studies on EU regulations of traditional herbal medicinal products have been conducted for more than 10 years, but there is still some cognitive bias and lack of research. In this paper, a review of the relevant research progress and the main misunderstanding problems about Directive 2004/24/EC, like the centralized and decentralized supervision system of traditional herbal medicinal products in the EU, marketing authorization procedures for traditional herbal medicinal products, Community Herbal Monograph and List Entries, would be systematically analyzed, so as to provide reference for the registration of Chinese patent medicine in EU.
ABSTRACT
The European Legislation Directive 2004/24/EC introduced a simplified registration procedure for traditional herbal medicinal products, which has largely reduced the difficulty of registration for herbal medicinal products. The traditional Chinese medicinal products still face a lot of challenges such as 15-year minimum medicinal use requirements in the European Union (EU) and limited self-medication indication categories and administration modes. As the criteria for a Community Herbal Monograph assessment is in many aspects similar to assessment of safety and efficacy aspects in the registration of a traditional herbal medicinal product, this article has made a systematic evaluation of the latest assessment of Community Herbal Monograph and presented the key issues in traditional Chinese medicinal product registration based on a Community Herbal Monograph perspective. The results from this article will ultimately contribute to supporting and assisting the non-European traditional herbal medicinal product registration in EU.
ABSTRACT
As European Union (EU) is one of the largest herbal markets in the world, EU registration is an important way for the internationalization of Chinese materia medica products. According to the current EU legislation, Chinese materia medica products can access to the EU market in the form of food supplements, drugs, cosmetics, and medical devices. This article discusses the main EU marketing approaches related regulations such as application of food supplements, well-established use (WEU), and traditional use (TU) of medicine. The purpose is to clarify the feasible way of EU registration for Chinese materia medica products and to provide reference for the Chinese enterprises which are aspiring to open up the EU market.
ABSTRACT
A highly sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of actinoside E in rat plasma. The analytes were extracted by ethyl acetate and an analogue of actinoside F was used as the internal standard. The mobile phase consisted of methanol-water (50: 50, V/V) containing 0.1% formic acid was delivered at a flow rate of 0.3 mL·min(-1) to a Zorbax SB-C18 column (100 mm × 2.1 mm, 3.5 μm). The detection was performed by electrospray ionization mass spectrometry in the negative multiple reaction monitoring mode with a chromatograph run time of 3.0 min. Calibration curves of actinoside E were linear in the range of 0.5-2 500 ng·mL(-1). In this range, intra- and inter-day precision ranged from 1.7% to 7.5% and 2.0% to 8.9%, respectively. The accuracy ranged from 95.7% to 108.6%, and extraction recovery from 83.2% to 85.5%. This method was successfully applied to a pharmacokinetic study of actinoside E in rats after intravenous (5 mg·kg(-1)) and oral (100 mg·kg(-1)) administration, and the results showed that actinoside E was poorly absorbed with an absolute bioavailability being approximately 0.27%.
Subject(s)
Animals , Male , Rats , Actinidia , Chemistry , Chromatography, High Pressure Liquid , Methods , Glycosides , Blood , Pharmacokinetics , Kaempferols , Blood , Pharmacokinetics , Plant Extracts , Blood , Pharmacokinetics , Rats, Sprague-Dawley , Sensitivity and Specificity , Tandem Mass Spectrometry , MethodsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of herba schizonepetae volatile oil (STO) on the activity of 5-lipoxygenase (5-LO), so as to elucidate its mechanisms of anti-inflammatory action which is related to the arachidonic acid (AA) metabolism.</p><p><b>METHOD</b>Thoracic cavity leukocytes from the pleurisy model rat induced by injecting 1%-carrageenan into the pleural cavity were collected. Then 0. 4 mL cell suspension including 2 x 10(7) cells per millilitre were used as the reaction system in vitro. STO in different concentrations (final concentration 0.011, 0.022, 0.043, 0.087, 0.179, 0.255, 0.364 g x L(-1)), zileuton (final concentration 0.625 x 10(-3) g x L(-1)), and DMSO in the same volume were added into the reaction tube respectively. The reaction tubes were incubated at 37 degrees C for 20 min and CaCl2 (final concentration 2 mmol x L(-1)), MgCl2 (final concentration 0.5 mmol x L(-1)), exogenous AA (final concentration 200 micromol x L(-1)) and A23187 (final concentration 5 micromol x L(-1)) were added in turns during this period. The reaction tubes were mixed and continuously incubated at 37 degrees C for 30 min. After terminating reaction by adding methanol, the metabolites of 5-LO, leukotriene B4 (LTB4) and 5-hydroxy-6, 8, 11, 14-eicosatetraenoic acid (5-HETE), were extracted, separated and detected by means of RP-HPLC.</p><p><b>RESULT</b>Compared with control group, STO significantly inhibited the biosynthesis of LTB4 and 5-HETE at final concentration between 0. 022 g x L(-1) and 0.364 g x L(-1) (P < 0.05 or 0.001) in dose dependence manner, and its IC50 value was 0.124 g x L(-1) and 0.142 g x L(-1) for LTB4 and 5-HETE, respectively.</p><p><b>CONCLUSION</b>STO can inhibited the activity of 5-LO, which is an important enzyme of AA metabolism, in rat thoracic cavity leukocytes in a dose-dependent manner in vitro. It is suggested that the mechanism of anti-inflammatory action of STO is related to its inhibiting the activity of 5-LO and decreasing the level of major inflammatory mediators LTB4.</p>
Subject(s)
Animals , Male , Rats , Anti-Inflammatory Agents , Pharmacology , Arachidonate 5-Lipoxygenase , Metabolism , Cells, Cultured , Drugs, Chinese Herbal , Pharmacology , Leukocytes , Oils, Volatile , Pharmacology , Plant Oils , Pharmacology , Rats, Sprague-Dawley , Thoracic Cavity , Allergy and ImmunologyABSTRACT
Objective: To search for a rapid and efficient method for the isolation of 3 kinds of isoflavone glucosides from the ethanol extract of Semen Sojae Praeparatum. Methods: The crude isoflavones were extracted by 75% aqueous ethanol after removing the oil by Soxhlet extraction. Then 1300 macroporous resin, water and different concentrations of aqueous ethanol (10%, 20%, 30%, 40%, 50%, 70%, and 95%) were used to separate and elute the crude isoflavones. The fraction eluted by 40% aqueous ethanol was subjected to preparative HPLC analysis. The chromatographic conditions: A YWG C18 (10.0 mm × 200 mm, i. d. 10 μm) column was used; the mobile phase consisted of acetonitrile-water-acetic acid at volume ratio of 25: 75: 1 (V/V/V) and a flow rate of 3.0 ml/min; the injection volume was 750 μl; and the detection wave length was set at 260 nm. Results: Daidzin, glycitin and genistin were rapidly separated with the purities over 99% as determined by external standard HPLC. Conclusion: This technique is simple and suitable for the isolation of daidzin, glycitin and genistin from Semen Sojae Praeparatum.