The aim of the study was to evaluate a cerebroprotective activity of the sitagliptin and aminoguanidine combination in rats with an acute and chronic cerebral circulation insufficiency, as well as with a traumatic brain injury.

Materials and methods. The study was carried out on male Wistar rats in 3 stages using, respectively, a model of a chronic pathology: a chronic cerebral circulation insufficiency (CCCI), as well as 2 models of the acute brain injury (BI): an acute cerebral circulation insufficiency (ACCI), and a traumatic brain injury (TBI). А CCCI was modeled by a bilateral stenosis of the common carotid arteries (by 50%), a model of a hemorrhagic stroke caused by an intracerebral injection of the autologous blood was used as a stroke, a TBI was modeled by a mechanical damage to the brain tissue. To assess the pathology course severity, the following tests were used: Adhesion test, Open field, Morris water maze test, as well as Garcia and Combs&D’Alecy scales. In the animals with an acute damage to the brain at the end of the experiment, the severity of edema of the affected hemisphere was also determined. The treatment was with sitagliptin (10 mg/kg), aminoguanidine (25 mg/kg), or a combination thereof. The obtained data were subjected to the statistical processing.

Results. In the course of the study, it was found out that the administration of a sitagliptin and aminoguanidine combination, unlike each of the components, had a cerebroprotective effect in the animals with a chronic or acute damage to the brain, reducing the severity of psychoneurological (cognitive and sensory-motor) disorders, as well as the brain edema.

Conclusion. Aminoguanidine, as an iNOS blocker, enhances the action of sitagliptin, preventing the brain edema development and reducing the neurological deficit severity (the severity of cognitive and sensory-motor impairments) in the animals with an acute and chronic cerebral circulation insufficiency.

The article reflects the results of the essential oils selection for the compositions with antibacterial and antifungal properties. The technology of their production is represented.

The aim of the work was the development of technology and the study structure of new essential oils compositions with antibacterial and antifungal activities.

Material and methods. The following plants have been used in the work: the herb of Hyssopus ambiguus (Trautv.) Iljin, the herb of Thymus crebrifolius Klokov, the herb of Thymus marschallianus Willd, the herb of Thymus serpyllum L., and the essential oils obtained from them. The composition of the essential oils was determined by Gas Chromatography Mass Spectrometry. The main physical and chemical parameters of the compositions were evaluated in accordance with the requirements of the Russian State Pharmacopoeia, the XIV^th edition. The tests for the antimicrobial activity were carried out using the strains of Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Candida albicans ATCC 10231.

Results. Compositions with an activity against microorganisms Staphylococcus aureus, Bacillus subtilis, Escherichia coli and fungi Candida albicans have been obtained and studied. The composition based on essential oils of Hyssopus ambiguus (Trautv.) Iljin and Thymus marschallianus Willd. contained 139 components, the main ones of which are eucalyptol (6.51%) and terpinen-4-ol (1.95%). The composition of essential oils of Hyssopus ambiguus (Trautv. Iljin) and Thymus crebrifolius Klokov contained 137 components (eucalyptol (20.37%), terpinen-4-ol (7.03%), Ʈ-muurol (2.28%), γ-terpinene (2.23%), β-myrcene (2.09%), etc.). The composition of the essential oils of Hyssopus ambiguus (Trautv.) Iljin and Thymus serpyllum L. contained 149 components (the main ones are eucalyptol (7.33%) and α-terpineol (0.9%)).

Conclusion. The technology has been proposed and the structure of the essential oils compositions with antibacterial and antifungal activities has been established.

Licorice herb (Glycyrrhiza glabra L.) is a promising herbal raw material, which can be comprehensively used to develop drugs with an anti-inflammatory action.

The aim of the article was to development a quantitative determination method of total flavonoids in Glycyrrhiza glabra L. herbs.

Materials and methods. The subjects of research were 5 samples of licorice herb harvested in summer in various places of growing and cultivation. Pinostrobin was used as a standard sample. The registration of the electronic spectra was carried out with a spectrophotometer (Analytik Jena AG, Germany) by differential spectrophotometry, 96% ethanol was used as a solvent.

Results. The methods for quantitative determination of total flavonoids in Glycyrrhiza glabra L. was carried out at an analytical wavelength of 310 nm equivalent to pinocembrin. The optimum parameters for the extraction of total flavonoids from Glycyrrhiza glabra L. were as follows: the extractant – 90% ethanol; the «raw material-extractant» ratio was 1:50; the extraction time was 60 min; the degree of atomization was 2 mm. The content of total flavonoids for the Glyccyrhiza glabra L. herb has been determined, it varies from 0.39±0.002 to 3.41±0.015% with the humidity of the vegetative raw material from 9.97±0.003 to 10.03±0.003% depending on the place of the vegetation, cultivation and year of the raw material collection. The error of the single determination with a 95% confidence level was ±0.73%.

Conclusion. The developed methods for the quantitative determination of total flavonoids in Glycyrrhiza glabra L. herbs can be used to solve the issues of standardization of these medicinal plant raw materials.

The aim of the work was to study сytokine response characteristics in the group of persons contacted by a novel coronavirus infection depending on the development of the disease over the next 14 days. Herewith, for the immunocorrection with a preparation based on RNA double-stranded sodium salt (RADAMIN®VIRO) causing a secondary reduction in the risk of COVID-19 in the analyzed group, potential targets had been selected.

Materials and methods. A double-blind, placebo-controlled study of the drug based on RNA double-stranded sodium salt therapeutic effects was conducted in a group of patients who had been in contact with the persons having a confirmed diagnosis of COVID-19. The method of enzyme immunoassay in dynamics was used to determine the content of interferons alpha and beta (IFNα and IFNβ, respectively), interleukin-1β and -10 (IL1β and IL-10, respectively) in the blood serum and saliva in the contact persons, with a retrospective assessment of changes depending on the administration of the drug or placebo, as well as the development of COVID-19.

Results. In the course of the presented study, it was demonstrated that the established content of IFNα (less than
28 pg/ml) and IFNβ (less than 12 pg/ml) in saliva on the 1^st–2^nd contact days is a predictor of an increased risk of developing COVID-19. Herewith, the increase degree in these immunoregulatory peptides in the interval of 2–3 contact days is important: IFNα and IFNβ allows leveling the negative prognosis in patients by 250% or more. The lowest rates (p <0.001) of INFα on the 1^st–2^nd contact days, as well as an increase of less than 21% by the 3^rd day, were observed in persons with a waist circumference of more than 80/94 cm (women/men). The incidence in this group was higher and amounted to 85% (16 out of 20 people). The predictor role of IL-1β and IL-10 in the blood and saliva in relation to the start of the infectious process was not revealed. The administration of drug based on RNA double-stranded sodium salt to the contact patients made it possible to correct the interferon response in the form of an increase in the content of IFNα and IFNβ, as well as to reduce the incidence in comparison with the placebo group.

Conclusion. Differences in the interferon regulation upon contact with SARS-CoV-2 in the form of lower INF α and β levels, as well as a slightly pronounced growth dynamics in the interval of the first 3 days, influenced the increased risk of developing COVID-19. RADAMIN®VIRO can be recommended as a means of post-exposure prophylaxis of COVID-19 for both medical institutions and for caregivers and / or contacts with COVID-19 patients.

The aim of the work was to analyze Russian and foreign experience in the regulation and application practice of “off-label” drugs in order to develop recommendations on the optimization of their application in clinical practice.

Material and methods. The analysis of scientific articles and legal documents of the Russian Federation and foreign countries published from 2011 to 2022 on the websites Consultant Plus, FDA, EMA, NCBI, e-library, as well as a qualitative sociological study conducted in May-August 2022 ‒ 11 in-depth interviews with experts in the field of the healthcare system of the Russian Federation.

Results. The social and economic aspects have been considered and the list of legal problems in the application practice of “off-label” drugs has been disclosed. A state analysis of the regulatory and legal framework on the drugs application practice by healthcare professionals in the absence of registered indications for “off-label” drugs use has been presented. The use of an unregistered medicinal product in the territory of the Russian Federation in everyday medical practice has been considered. The analysis of the Russian and foreign experience in regulating the use of drugs in the absence of their registration in the country, as well as the absence of registration of some indications for their prescription in the instructions for the medical use of such drugs has been also carried out. The authors have formulated the key problems of the use of “off-label” drugs in clinical practice. Based on the results of the in-depth interviews, the recommendations of the expert community on the ways to optimize the use of “off-label” drugs have been identified and concretized.

Conclusion. The results of this study made it possible to formulate recommendations for expanding the ability of specialists to prescribe “off-label” drugs treatment while maintaining a proper degree of the state control over this process: a legislative consolidation of the regional health authorities’ obligations and responsibilities on the drug provision; creating an open and transparent system for the “off-label” drugs use by patients and their legal representatives, the mandatory full information of the patient about the fact of using the “off-label” drug, as well as the risk and nature of the development of possible adverse reactions. When prescribing these drugs, the patient safety should be the top priority.

The aim of the work was to study the legal aspects of the legislative regulation for manufacturing medicines in a pharmacy organization.

Materials and methods. Databases of ConsultantPlus, Cyberleninka, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Center for Biotechnology Information (NCBI), PubMed, e-library, WIPO Lex were used as search sources. The search was based on the following keywords and phrases: intellectual property, pharmacies+invention, patent, drugs, extemporal+production, orphan+diseases, as well as their Russian counterparts. 133 sources of information, including scientific articles and regulations, were found out; 50 have been included in this review. The analysis of information sources published from 2013 to 2023, was determined by the peculiarities of legislation changes in this area.

Results. The article provided an overview of modern, including regulatory practice, pharmaceutical manufacturing in the Russian Federation, and also analyzed the benefits of this activity for the medical community, patients and the state. At the same time, the individualization of drug treatment has made it possible to work out systemic solutions for developing drug therapy methods for special groups of patients for whom the economic feasibility of a pharmaceutical registration and launching such drugs onto the market has been brought into challenge. In addition, pharmacy manufacturing is an accessible tool in the study of the drugs prescribed by a doctor not in accordance with the instructions for medical use (off-label) or in the dosage forms/dosages that are not on the market. Extemporaneous manufacturing can be also a part of the process of “repositioning” drugs on the market, subject to compliance with the requirements for pharmacy manufacturing and control of the prescribed drugs safety. The possibility of pharmaceutic drug manufacturing also makes it possible to partially resolve issues related to intellectual property. As a result of the carried out analysis, the following hypothesis was confirmed: the legislative changes have a similar legal assessment both in Russia and abroad and correspond to the legal practice in resolving intellectual property issues in relation to pharmacy organizations.

Conclusion. The renewal of a pharmacy production will improve the availability of the drug care to the population, taking into account individual dosages and dosage forms in various therapeutic areas, and can also become a tool for repositioning drugs or clinical testing of new molecules for rare incurable diseases.