This publication presents the views of Nikolay I. Sidelnikov, Academician of the Russian Academy of Sciences, Director of the All-Russian Scientific Research Institute of Medicinal and Aromatic Plants, on the current developments in the cultivation of medicinal plants, the search for and study of herbal drug sources, and the development of herbal medicinal products. The All-Russian Scientific Research Institute of Medicinal and Aromatic Plants carries out comprehensive studies of medicinal plants, including the evaluation of natural resources in the context of environmental management, the development of agricultural technologies, the search for biologically active substances, preclinical pharmacology and toxicity studies, and the development of technologies for the production of active substances and medicinal.

This article covers procedures for transitioning to the common market of the Eurasian Economic Union (EAEU), with a focus on low-margin yet high-demand medicines, including herbal medicinal products. First, the article analyses applicant engagement in aligning the dossiers for nationally authorised medicinal products with the requirements of the EAEU authorisation procedures. Then, the article describes the legislative  changes  introduced  to  ease  authorisation  requirements.  Finally, the author provides recommendations for applicants.

INTRODUCTION. The lack of a unified approach to establishing generic (grouping) names, which must be specified for herbal medicinal products, presents a challenge to developers and manufacturers preparing registration dossiers, as well as to regulators reviewing their submissions.

AIM. This study aimed to set forth common approaches to establishing generic names for herbal medicinal products based on studying the terminology used in different legal systems.

DISCUSSION. The authors analysed the pharmaceutical terminology used for herbal medicinal products at national and  supranational  levels  in  the  Russian  Federation, the Eurasian Economic Union (EAEU), the Republic of Belarus, the European Union (EU), the United Kingdom, and the United States. This analysis revealed differences in the terminology used in the Russian Federation and the EAEU. For example, the definition of “herbal drugs” is more detailed in the EAEU documents than in the Russian documents, and the definitions of “herbal drug preparation” and “herbal medicinal product” are not the same as well. The authors analysed the approaches to generic naming of herbal medicinal products and detected some improperly formed generic names in the regulatory documentation and Russian State Register of Medicinal Products. In addition, the study revealed variability in generic names proposed by different manufacturers for medicinal products having the same trade name. The authors described the selection of generic names for herbal medicinal products, including fatty or essential oils and liquid or dry extracts. The authors touched upon generic naming of some types of source plants when the morphological group of the herbal drug or the name of the source plant is ambiguous, the Latin name and the Russian name of the herbal drug are inconsistent, or the Latin name of the resulting product or the morphological group of the herbal drug is erroneous. The authors systematised and unified approaches to generic naming of herbal medicinal products with due regard to the species of source plants, the morphological groups of herbal drugs, and the production technology and composition of herbal medicinal products. The authors analysed typical errors in establishing conventional and generic names for herbal drugs and herbal medicinal products associated with incorrectly identified morphological groups of herbal drugs, incorrect source plant names, mismatching structures of Latin and Russian names of herbal drugs, erroneous Latin names of the resulting products, or wrongly assigned morphological groups of herbal drugs.

CONCLUSIONS. According to the analysis of  the  names  of  herbal  drugs,  herbal drug preparations, and herbal medicinal products used in  the  State  Pharmacopoeia of the Russian Federation (editions XI–XV), the Pharmacopoeia of the EAEU, and the European Pharmacopoeia, the terminology of these legal systems is harmonised to a high degree. The alignment of terminology is the closest between the regulatory documents of  the  EAEU  and the EU. The terms and names used in Russia need further unification. The results of this study can be used in Russian pharmacopoeial practice to develop regulatory documents, prepare  registration dossiers, and conduct expert reviews of submissions for herbal medicinal products.

INTRODUCTION. It is important to  study  medicinal  plants  that  are  not  listed  in the State Pharmacopoeia of the Russian Federation but are used in traditional medicine and represent an abundant source of raw materials.

AIM. This study aimed to collate data on the composition and pharmacology of the biologically active substances contained in shrubby cinquefoil (Pentaphylloides fruticosa (L.) O. Schwarz).

DISCUSSION. According to the reviewed literature, the underground and aboveground parts of P. fruticosa contain flavonoids, tannins, phenolic acids, triterpenoid saponins, and other compounds with significant therapeutic potential, which show antimicrobial, anti-inflammatory, and immunomodulatory properties. Most pharmacology studies of P. fruticosa bioactive metabolites investigate the modulating action they exert on innate and adaptive immune responses via various mechanisms. The majority of studies use different techniques and focus on the properties of crude extracts from morphologically different parts of the plant, which precludes meaningful comparisons of the results obtained in these studies.

CONCLUSIONS. P. fruticosa is a promising medicinal plant for inclusion in the pharmacopoeia. The plant has clinical potential as an antioxidant and an immunomodulator for the prevention and treatment of many diseases. The standardisation of Р. fruticosa herbal drugs requires thorough studies. The chemical composition of various plant tissues should be analysed with due consideration of seasonal, climatic, and anthropogenic factors.

INTRODUCTION. The influence of anthropogenic factors on the content of toxic elements in plants increases the need for monitoring the content of toxic elements in medicinal plant raw materials and the corresponding herbal medicinal products. In addition, studying the elemental composition of herbal medicinal products will help determine their potential in the treatment of elemental metabolism disorders (macroand micro-elementoses).

AIM. This study aimed to determine the elemental composition and the heavy metal content in Pectoral Species No. 2 and its components.

MATERIALS AND METHODS. The study used Pectoral Species No. 2 and its components, including common coltsfoot (Tussilago farfara L.) leaf, greater plantain (Plantago major L.) leaf, and liquorice (Glycyrrhiza glabra L., G. uralensis Fisch.) root. The samples were manufactured by Krasnogorskleksredstva JSC and purchased at Moscow pharmacies. To determine the elemental composition, the study samples were digested with concentrated nitric acid and analysed by inductively coupled plasma mass spectrometry (ICP-MS). The calibration involved using concentrations ranging from 0.5 to 1.5 times the maximum permissible concentration for each element.

RESULTS. This study identified and quantified 26 elements in Pectoral Species No. 2 and its components. The content of heavy metals was within the permissible concentrations. The study established the predominant macronutrients (potassium, calcium, and magnesium), micronutrients (iron, aluminium, and strontium), and ultramicronutrients (barium, nickel, and chromium) in Pectoral Species No. 2. The authors evaluated the contributions of each herbal drug to the total element content in the medicinal product.

CONCLUSIONS. Coltsfoot leaf exerts the greatest influence on the content of macro-, micro-, and ultramicronutrients in Pectoral Species No. 2. Greater plantain leaf contributes the most to the zinc, silver, and nickel content. Liquorice root has the highest strontium and molybdenum content.

INTRODUCTION. Current scientific research aims to discover new plant sources of hydroxycinnamic acids for the development of novel medicinal products. Most commonly, the quantitative determination of hydroxycinnamic acids in herbal drugs involves testing procedures based on spectrophotometry and its modifications.

AIM. This study aimed to establish the possibility of the quantification of hydroxycinnamic acids in herbal drugs by direct spectrophotometry.

DISCUSSION. This review presents organised information on the use of direct spectrophotometry to quantify hydroxycinnamic acids in 70 plant species growing or cultivated in the Russian Federation. The review covers publications in Russian for the period from 2007 to 2023. According to the reviewed publications, direct spectrophotometry is an easy-to-use and highly reproducible method that does not require additional reagents or labour-intensive steps. Direct spectrophotometry may result in an overestimation of the hydroxycinnamic acid content due to overlapping absorption bands of polyphenolic compounds with different structures.

CONCLUSIONS. Direct spectrophotometry can be considered as a method for measuring the total content of phenolic compounds (as well as hydroxycinnamic acids) in herbal drugs. Different approaches to direct spectrophotometric quantification of hydroxycinnamic acids in herbal drugs by can serve as a methodological basis for developing analytical procedures specific to the chemical compositions of biologically active compounds in herbal drugs and their extracts.

INTRODUCTION. Polyphenolic compounds of various classes have pronounced absorption bands overlapping in almost the same ultraviolet region. This superposition of bands complicates the quantification of total hydroxycinnamic acids in herbal drugs by direct spectrophotometry without additional sample preparation.

AIM. This study aimed to establish the possibility of quantifying hydroxycinnamic acids in herbal drugs by spectrophotometry in the presence of other polyphenolic compounds.

DISCUSSION.  This  review  analyses  publications   on   analytical   procedures   for the spectrophotometric quantification of hydroxycinnamic acids that are based on the preliminary separation or chemical modification of polyphenolic compounds (combining the use of spectrophotometry, chromatography, extraction, Arnow’s reagent, etc.). The described sample preparation can help to resolve absorption bands in the spectra of polyphenolic compounds. The results of assessing the characteristic parameters of these analytical procedures (selectivity, sensitivity, labour intensity, etc.) can serve as a basis for searching novel approaches to the quantitative determination of hydroxycinnamic acids in plants.

CONCLUSIONS. To determine the content of hydroxycinnamic acids in mixtures of polyphenolic compounds, analysts may use special sample preparation (combining spectrophotometry with chromatography and extraction) or chemical modification of the initial compounds. The acquired spectra could benefit from specific mathematical processing (derivative photometry and Vierordt’s method). However, even with the abovementioned approaches, it may not always be possible to increase the selectivity of an analytical procedure. Therefore, there is a need to further improve existing analytical procedures for the quantification of hydroxycinnamic acids and develop new ones.

INTRODUCTION. Currently the development of novel resourceand cost-effective extraction techniques for herbal medicinal products is a priority for pharmaceutical technology. A unique position among these herbal medicinal products belongs to the medicinal products of Echinacea purpurea, which stimulate the innate immune system.

AIM. The study aimed to investigate the effect of E. purpurea herb defatting on the extraction of hydroxycinnamic acids (HCAs) from the herbal drug and to evaluate the suitability of this treatment for the production of E. purpurea tinctures.

MATERIALS AND METHODS. On the basis of previous  experimental  findings, heptane was chosen as the defatting solvent. The production of E. purpurea tinctures included an additional step of herbal drug heating. The content of total HCAs was determined using a pharmacopoeial method, while the content of individual HCAs was determined using high-performance liquid chromatography. The residual defatting solvent was quantified by gas chromatography. The experiment used reference standards for HCAs.

RESULTS. The study showed that a single one-hour defatting treatment of the herbal drug with heptane at a 1 g to 5 mL ratio increased the yield of HCAs extracted from Е. purpurea herb. The optimal production process for E. purpurea tinctures involved grinding the herbal drug to 500–2000 μm, macerating the powder with 60% ethanol (v/v) at a 1 g to 10 mL ratio for 7 days, mechanically stirring the mixture for 60 min, and settling the crude extract for 3 days. Heating the herbal drug prior to extraction resulted in the highest yield of HCAs.

CONCLUSIONS. The newly developed production technology for E. purpurea tinctures with a preliminary defatting step increases the HCA content in the tinctures. This technology can be used for the industrial production of tinctures high in HCAs.

INTRODUCTION. The determination of impurities is a key requirement for the quality assessment of medicines because impurities can significantly impact the quality and therapeutic effectiveness. Pharmacopoeias are the most  important  scientific and methodological guidelines for manufacturers developing medicinal product specifications and regulators assessing these specifications as part of registration dossiers. Therefore, it is essential to harmonise national and international approaches to impurities.

AIM. This study aimed to analyse and summarise pharmacopoeial requirements for and methodological approaches to the control, evaluation, and identification of organic impurities in medicines.

DISCUSSION. The authors compared requirements for the control of organic impurities in small-molecule medicines set forth in national and international pharmacopoeias and guidelines of the International Council for Harmonisation of Technical Requirements for Medicinal Products for Medical Use (ICH) and the Eurasian Economic Union (EAEU). This comparison highlighted the differences in current approaches that require further harmonisation of the existing regulatory documentation. Additionally, this study analysed the popularity, advantages, and disadvantages of different options for determining impurities in two-component combination products (i.e. identified and/or unidentified impurities in one or each of the active substances). The analysis demonstrated the need to control nitrosamines and genotoxic impurities and to use selective and highly sensitive chromatographic methods.

CONCLUSIONS. When drafting  pharmacopoeial  monographs  for  medicinal products, experts should consider the general approach set forth in the EAEU pharmacopoeia and regulations and in the ICH Q3B guideline. This approach recommends that process-related impurities of active substances should not be controlled at the medicinal product level. Therefore, pharmacopoeial monographs for active substances should distinguish degradation products from process-related impurities. Impurities should be determined for each active substance to ensure the quality and safety of fixed combination medicinal products. Priorities for improving the methodological approach to the control of organic impurities include using reference standards for impurities and acknowledging the necessity of impurity quantification.

INTRODUCTION. The evolution of the influenza virus has led to a gradual decrease in the effectiveness of current antivirals. Better methods of prevention, detection, control, and treatment of influenza are needed, including more effective vaccines and antivirals. At the moment, the Russian Federation and the Eurasian Economic Union lack documents regulating the conduct of clinical trials of medicinal products for  influenza  prevention  and  require  that  guidelines  should  be  developed  for the matter.

AIM. The authors aimed to analyse the main regulatory approaches to preclinical and clinical development programmes for medicinal products for influenza prevention in the Russian Federation, the Eurasian Economic Union (EAEU), the European Union, and the United States of America.

DISCUSSION. This review substantiates the importance of non-specific influenza chemoprophylaxis in reducing the risk of adverse outcomes of the disease. The authors analysed the main stages of preclinical development of medicinal products for influenza prevention and  the  potential  contribution  of  preclinical  studies  to the planning of clinical trials. When developing preclinical and clinical programmes for medicinal products for influenza prevention, it is necessary, first of all, to take into account the requirements of the national good clinical practice guidelines and the EAEU guidelines for clinical trials in general. This article pays particular attention to the clinical trial designs used internationally, the possible options for their implementation, the characteristics of study populations, the formation of study groups, and the selection of primary and secondary endpoints.

CONCLUSIONS. The article proposes approaches to planning and conducting clinical trials of medicinal products for the prevention of influenza, taking into account the specifics of legal norms and clinical traditions of Russian practice. These recommendations will ensure high-quality data on the effectiveness and safety of investigational medicinal products and accelerate the introduction of new effective medicinal products for influenza prevention into medical practice.