Analysis of simplified registration of traditional herbal medicinal products in European Union / 国际中医中药杂志

Europe occupies an important position in the world herbal medicine market. The registration of Traditional Chinese Medicine (TCM) in EU is of great significance to the internationalization of TCM. The European Medicines Agency (EMA) has designed a relatively complete management system and regulatory guidelines for the registration and supervision of herbal medicinal products. The promulgation of the DIRECTIVE 2004/24/EC (2004 / 24 / EC) indicates that TCM could enter the EU market through simplified registration. Based on the registration conditions, registration authority and document guideines of Traditional Herbal Medicinal Products (THMPs) in EU, this paper analyzes the application requirements of simple registration of traditional herbal products in EU, and provides suggestions for the simplified registration of TCM in EU according to the registration requirements of medicinal history, quality requirements and application data format.

Biomonitoring for traditional herbal medicinal products using DNA metabarcoding and single molecule, real-time sequencing

Global concerns have been paid to the potential hazard of traditional herbal medicinal products (THMPs). Substandard and counterfeit THMPs, including traditional Chinese patent medicine, health foods, dietary supplements, etc. are potential threats to public health. Recent marketplace studies using DNA barcoding have determined that the current quality control methods are not sufficient for ensuring the presence of authentic herbal ingredients and detection of contaminants/adulterants. An efficient biomonitoring method for THMPs is of great needed. Herein, metabarcoding and single-molecule, real-time (SMRT) sequencing were used to detect the multiple ingredients in Jiuwei Qianghuo Wan (JWQHW), a classical herbal prescription widely used in China for the last 800 years. Reference experimental mixtures and commercial JWQHW products from the marketplace were used to confirm the method. Successful SMRT sequencing results recovered 5416 and 4342 circular-consensus sequencing (CCS) reads belonging to the ITS2 and regions. The results suggest that with the combination of metabarcoding and SMRT sequencing, it is repeatable, reliable, and sensitive enough to detect species in the THMPs, and the error in SMRT sequencing did not affect the ability to identify multiple prescribed species and several adulterants/contaminants. It has the potential for becoming a valuable tool for the biomonitoring of multi-ingredient THMPs.

Research and practice on readability test of Danshen Capsule for registration as THMPs in EU / 中草药

The package leaflet is a legal document relevant with drug information, which plays an important role for instructing the rational use of the medicinal product for the patient population. During the registration application in the EU countries, the patient readability test on package leaflet is the essential requirement to ensure the leaflet information easy-to-understand and avoid any risk caused by misunderstanding. The readability research on package leaflet can improve its quality and drug use safety to patients. Currently, CFDA does not publish any regulation/guidance on the drug application in China. By the successful case of registration application of Danshen Capsule as the herbal medicine in the EU, this paper not only discusses the relevant requirements of readability test in the EU, but also offers the regulatory advice on future regulations of readability research of the pharmaceutical products in China.

Screening and verifying potential NTCP inhibitors from herbal medicinal ingredients using the LLC-PK1 cell model stably expressing human NTCP / 中国天然药物

NTCP is specifically expressed on the basolateral membrane of hepatocytes, participating in the enterohepatic circulation of bile salts, especially conjugated bile salts, to maintain bile salts homeostasis. In addition, recent studies have found that NTCP is a functional receptor of HBV and HDV. Therefore, it is important to study the interaction between drugs and NTCP and identify the inhibitors/substrates of NTCP. In the present study, a LLC-PK1 cell model stably expressing human NTCP was established, which was simple and suitable for high throughput screening, and utilized to screen and verify the potential inhibitors of NTCP from 102 herbal medicinal ingredients. The results showed that ginkgolic acid (GA) (13 : 0), GA (15 : 1), GA (17 : 1), erythrosine B, silibinin, and emodin have inhibitory effects on NTCP uptake of TCNa in a concentration-dependent manner. Among them, GA (13 : 0) and GA (15 : 1) exhibited the stronger inhibitory effects, with IC50 values being less than 8.3 and 13.5 μmol·L(-1), respectively, than the classical inhibitor, cyclosporin A (CsA) (IC50 = 20.33 μmol·L(-1)). Further research demonstrated that GA (13 : 0), GA (15 : 1), GA (17 : 1), silibinin, and emodin were not substrates of NTCP. These findings might contribute to a better understanding of the disposition of the herbal ingredients in vivo, especially in biliary excretion.

Avaliação do potencial biológico da Tabebuia aurea (Silva Manso) como fonte de moléculas bioativas para atividade antimicrobiana, antiedematogênica e antirradicalar / Biological potential assessment of Tabebuiaaurea (Silva Manso) as a source of bioactive molecules for antimicrobial, antiedematogenic and antiradical activity

RESUMO As espécies da família Bignoniaceae e do gênero Tabebuia são amplamente utilizadas na medicina tradicional e possuem um forte potencial terapêutico. Diante disso, objetivou-se avaliar o potencial biológico da Tabebuia aurea, determinando a atividade antimicrobiana; por meio do método da microdiluição em caldo, para a determinação da Concentração Inibitória Mínima (CIM); antiedematogênica, pelo ensaio de edema de orelha induzido por capsaicina; e antirradicalar, frente ao radical DPPH. Os extratos etanólicos de T. aurea não evidenciaram citotoxicidade, exceto o extrato etanólico da flor nas concentrações > 0,5 mg mL-1. O extrato etanólico da flor foi ativo com ação bactericida frente a S. epidermidis (CIM de 0,06 mg mL-1) enquanto o extrato etanólico da folha foi moderadamente ativo frente a S. epidermidis (CIM: 0,25 mg mL-1) e S. aureus (CIM: 0,50 mg mL-1) sugerindo ação bacteriostática para ambas as linhagens. Os dois extratos apresentaram ação antiedematogênica, com inibição do edema de 40,50% pelo extrato etanólico da flor e de 41,73% pelo extrato da folha. T. aurea não apresentou atividade antirradicalar. Os resultados comprovam o perfil antibacteriano e antiedematogênico com ausência de citotoxidade pela T. aurea. Sugere-se a continuação dos testes com frações e substâncias isoladas das flores e folhas da referida espécie vegetal, bem como de experimentos in vivo, como forma de agregar evidências visando à busca de novos fitoterápicos.

ABSTRACT The species of Bignoniaceae family and genus Tabebuia are widely used in the traditional medicine and have a great therapeutic potential. The aim of the current research was to evaluate the biological potential of the Tabebuia aurea, determining its antimicrobial activity by the microdilution broth method, to predict the anti-edematogenic Minimum Inhibitory Concentration (MIC) by ear edema assay induced by capsaicin; and the antiradical one, towards DPPH. The ethanol extracts of T. aureashowed no cytotoxicity, except for the flower ethanol extract in concentrations above > 0.5 mg mL-1. The ethanol extract of the flower was active, with bactericidal action, against S. epidermidis (MIC 0.06 mg ml-1) and the ethanol extract of moderately active recto S. epidermidis (CIM: 0.25 mg mL-1) and S. aureus (MIC: 0.50 mg mL-1) were bacteriostatic for both strains. Both extracts had antiedematogenic action on the inhibition of edema of 40.50% by the ethanol extract of the flower and 41.73% by leaf extract. T. aurea did not show antiradical activity. The results indicate the antibacterial and antiedematogenic profile with no cytotoxicity by the T. aurea. It suggests the continuation of tests with isolated fractions and substances of flowers and leaves of that plant species as well as in vivo trials, in order to enhance the evidences targeted on finding new herbal medicines.

Herbal Reference Standards: applications, definitions and regulatory requirements

This review concerns the definitions and appropriate analytical characterisations of herbal reference standards within the framework of regulatory requirements. It describes currently applicable rules and regulations, as well as future issues relating to the European Pharmacopoeia and United States Pharmacopoeia. It provides an update on the use and availability of pharmacopoeial (EP and USP) herbal reference standards since our last review was published in 2009. The continuing challenges facing manufacturers, suppliers and analysts are discussed on the basis of exemplary reference substances for herbal products in medicinal and food products. The article also reviews the special aspects of Brazilian stipulations (Brazilian Pharmacopoeia, Anvisa) by comparison with European regulations. The term herbal products as used throughout this article refers to herbal drugs, herbal preparations and finished herbal medicinal products unless a different meaning is obvious from the context. More specific terms are used where necessary.

The suggestions on the entry of Chinese medicines into European Community monographs for traditional herbal medicinal products / 国际中医中药杂志

Directive 2004/24/EC of the European Parliament and the Council entered into force on April 30th, 2004. After 7 years, there is no Chinese medicine to be registered successfully in European market as traditional herbal medicinal products. The thesis gives some ideas to tackle this problem. Procedure for the Preparation of Community Monographs for Traditional Herbal Medicinal Products (EMEA/HMPC/182320/2005) published by European Medicines Agency is an important guidance for traditional herbal products to enter European Community monographs. The thesis introduces and details the procedure as well as gives feasible suggestions about the procedure. It suggests that Chinese medicines enter European Community monographs first, and then apply the registration according to the directive 2004/24/EC. This is an easier access to European market.

Avaliação da qualidade de amostras comerciais de boldo (Peumus boldus Molina), pata-de-vaca (Bauhinia spp.) e ginco (Ginkgo biloba L.) / Control quality evaluation of commercial samples of boldo (Peumus boldus Molina), pata-de-vaca (Bauhinia spp.) and ginkgo (Ginkgo biloba L.)

O presente trabalho procurou avaliar a qualidade de produtos comercializados à base de boldo, pata-de-vaca e ginco, através dos parâmetros contidos na Farmacopéia Brasileira e na literatura específica. Foram analisadas oito amostras de boldo, nove de pata-de-vaca e sete de ginco, adquiridas em farmácias na cidade do Recife. A metodologia consistiu em avaliar: os rótulos e bulas dos produtos verificando se estavam de acordo com a RDC n o 17 de 24/02/2000 e a portaria 110/97 da ANVISA; realizar análise sensorial; verificar a autenticidade das amostras e sua pureza. Todas as embalagens de boldo, pata-de-vaca e seis de ginco continham erros ou ausência de informações científicas, além da falta de bula. Na verificação de impurezas, todas as de boldo, cinco de pata-de-vaca, e uma amostra de ginco foram reprovadas. Todos os produtos analisados apresentaram alguma irregularidade segundo os códigos oficiais, sendo necessário uma maior intensificação na vigilância de produtos à base de plantas medicinais no Brasil.

This study aimed to evaluate the quality of commercial products prepared with boldo (Peumus boldus Molina), pata-de-vaca (Bauhinia spp.) and ginkgo (Ginkgo biloba L.) by using parameters from the Brazilian Pharmacopoeia and specific literature. Eight samples of "boldo", nine of "pata-de-vaca", and seven of ginkgo were analyzed, all bought from pharmacies in Recife (Pernambuco, Brazil). The methodology consisted in evaluating the products’ labels and instructions to verify their accordance to RDC n o 17 of 02/24/2000 and ANVISA (National Sanitary Surveillance Agency) decree 110/97, undertaking a sensorial analysis, and verifying the authenticity and purity of the samples. All of the packages of "boldo" and "pata-de-vaca" and six of the packages of ginkgo contained mistakes or lacked scientific information; instructions were also missing. After analyzing for impurities, all samples of "boldo", five of "pata-de-vaca", and one of ginkgo were rejected. All of the products analyzed had some sort of irregularity in relation to the official codes, making it necessary to intensify the inspection of medicinal plant products in Brazil.