On November 9, 2022, between the Government of the Perm Territory, the Perm State Pharmaceutical Academy of the Ministry of Health of Russia (hereinafter referred to as PGFA) and the Autonomous Non-Profit Organization "Perm Scientific and Educational Center of the World Level "Rational Subsoil Use" (hereinafter referred to as the Perm REC) signed an Agreement on the establishment of the Perm Center cluster development of the pharmaceutical industry "PARMA" (hereinafter - CKR PARMA). The purpose of the Agreement is to create a material and technical, scientific, technological and intellectual environment that ensures the provision of a wide range of educational and scientific services within the framework of the full life cycle of pharmaceutical products (from development to sales).

In 2022, the Perm State Pharmaceutical Academy (PSFA) celebrates its 85th anniversary. The Academy's museum is the guardian of the Academy's history. The objectives of the museum are: accumulation and preservation of memory about the development of the university, its significant graduates, dissemination of information about the history of the university among students, graduates, applicants and other groups of visitors. At the same time, the PGFA museum also analyzes data characterizing individual stages in the history of the emergence and functioning of the university. Carrying out such an analysis allows one to find and evaluate the development trends of the university, to choose the directions for the development of individual areas of activity that could be used again. The purpose of the study Identification and analysis of development trends of the Perm State Pharmaceutical Academy in the period from 1937 to 2022. The following were used as objects of study: orders for the university, stored in the archives of the PSFA; university reports stored in the archives of the PGFA museum; protocols of party meetings, newspaper and magazine publications, memoirs of university veterans. The research methods were: documentary analysis, methods of one-factor analysis: summary, grouping. In the course of the study, the historical periods of the existence of the Perm State Academy as an independent pharmaceutical university were studied. The positions of collecting and evaluating individual parameters of the characteristics of the university's activities are proposed and used. This made it possible to evaluate changes in the activities of the university in terms of the proposed positions. An analysis of the activities of the Perm State Pharmaceutical Academy of historical periods was carried out. A large amount of factual material has been collected and analyzed in such sections as: university management, development of the material and technical base, forms of student education, areas of scientific research, educational work of students, and others.

Experts discussed current opportunities for pharmaceutical development in our country, discussed actual difficulties and the ways for overcoming it.

Introduction. The state of hypoxia, causing damage and cell death, underlies many pathological processes. In addition, hypoxia induces a state of free radical oxidation, which enhances the damaging effect of hypoxic damage. This necessitates the synthesis of new compounds and the creation on their basis of drugs with antihypoxic activity.

Aim. The aim of this study is the synthesis and study of the antihypoxic activity of 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2Н-pyrido[4,3,2-de] quinnolin-3-ones.

Materials and methods. Compounds of the 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2H-pyrido[4,3,2-de]quinnolin-3-ones series were obtained as a result of the interaction of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids c o-tolyl-, p-tolyl-, p-fluoro-, p-nitro-, 2,4,6-trichlorophenylhydrazines. As a result, 10 substances were synthesized, the structure of which was confirmed by IR and ¹H NMR spectroscopy. The study of the antihypoxic activity of the obtained compounds was carried out using the method of normobaric hypoxia with hypercapnia («hypoxia in a jar»).

Results and discussion. The studied compounds have different effects on the lifespan of mice under conditions of acute normobaric hypoxia with hypercapnia. Compounds IIIi and IIId, respectively, increased the lifespan of mice most significantly by 26.36 % and 25.64 %, respectively, compounds IIIa, IIIb, IIIg were less significant, compounds IIIc and IIIf had no effect, and compound IIIj had a prohypoxic effect.

Conclusion. Compounds with the most pronounced antihypoxic and antioxidant properties have been identified. Thus, further synthesis and study of 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2H-pyrido[4,3,2-de]cinnolin-3-ones is reasonable.

Introduction. Modern therapy defines oxidative stress as one of the key links in the pathogenesis of different diseases, which makes the search for new low molecular weight antioxidants actual [1]. The widely used methods are imperfect, since they reflects reactivity of the sample under artificial conditions [2–4]. The proposed technique of using the "Ecolum" biosensor makes it possible to preserve the advantages of in vitro methods and improve the accuracy of determination through the use of biological reactions of cells [5, 6].

Aim. Studying of the antiradical and antioxidant activity of 2-aminopyrroles, using in vitro methods and quantum-chemical calculations.

 Materials and methods. Earlier, derivatives of 2-aminopyrroles were obtained. Antiradical activity of the compounds was studied using the DPPH test (2,2-diphenyl-1-picrylhydrazyl). Antioxidant activity was evaluated on the model of oxidative stress using the «Ecolum» biosensor. The calculation data of the indices of reactivity in the approximation of the gas phase were obtained using quantum-chemical methods.

Results and discussion. The antioxidant activity test indicated a higher antioxidant potential of 2a, compared to 2b. Antiradical activity test revealed a greater antiradical potential of 2b. Quantum-chemical calculations showed that 2b is characterized by a higher ionization potential, which may indicate its greater resistance to oxidation compared to 2a.

Conclusion. The study of the antiradical and antioxidant activity of 2-aminopyrroles showed the importance of developing a methodology for the search for new antioxidants, because of antiradical activity test deviations, compared to living cell reactions.

Introduction. In recent years, there has been an increase in fundamental interest in the search for effective, including microbiological, methods for processing pharmaceutical waste to obtain new biologically active compounds on their basis. Our results showed that the product of bacterial degradation of paracetamol (BDP) exhibits pronounced stimulating properties in relation to medicinal plants of the families Plantaginaceae, Lamiaceae, Urticaceae, Linaceae and can be used as an inducer of the accumulation of biologically active substances in them.

Aim. The purpose of this work is to study the effect of BDP on the dynamics of biomass accumulation and the content of flavonoids in the flowers of Calendula officinalis L., fam. Asteraceae in comparison with the control (water) and growth stimulator "Zircon".

Materials and methods. BDP obtained on the basis of the Laboratory of Alkanotrophic Microorganisms Institute of Ecology and Genetics of Microorganism UB RAS (Perm). Calendula officinalis flowers collected from plants treated with BDP and Zircon growth stimulator were used to study the dynamics of dry biomass accumulation and changes in the content of flavonoids by the spectrophotometric method. For a comparative analysis of the intensity of the increase in the biomass of flowers during the treatment of plants with these agents, as well as to predict the accumulation of flavonoids, kinetic modeling was used.

Results and discussion. The total biomass harvest of calendula officinalis flowers when treated with BDP increased by 55 %, and when treated with the Zircon growth stimulator, by 24 % compared to the control. The content of flavonoids in flowers when treated with these agents increased by 101 and 40 %, respectively. The dates for the beginning of the collection of calendula officinalis flowers in the conditions of the Western Urals were determined: with the use of the Zircon growth stimulator – from July 20, BDP – from August 1, without treatment with growth stimulants – from August 14. Both stimulants increase the end date of the collection of raw materials by 10 days.

Conclusion. The product of bacterial degradation of paracetamol has a pronounced stimulating effect on calendula officinalis, significantly increasing the biomass of flowers and the content of flavonoids in them compared to the control (water) and growth stimulator "Zircon". With the use of kinetic modeling, the values of the parameters of the growth rate of the biomass of plant raw materials during the treatment of plants with these agents were established, a forecast was made for the accumulation of flavonoids, and the timing of the collection of calendula officinalis flowers in the conditions of the Western Urals was substantiated.

Introduction. New potential biologically active compounds with different pharmacological activities were found among pyrimidine derivatives. Simple and available synthesis of tetrahydropyrimidine-5-carboxamides was developed in Perm State Pharmaceutical Academy. Products of this reaction previously shown high analgesic and anti-inflammatory activities.

Aim. To get previously unknown functionalized pyrimidines and to study their analgesic, anti-inflammatory and antipyretic activities.

Materials and methods. 11 compounds N,6-diaryl-4-methyl-2-thioxo-1,2,3,6-tetrahydropyrimidine-5-carboxamides are objects of research. Their structure has been confirmed by spectroscopy methods. The biological activities were carried out by recommended methods for preclinical study of new pharmacological substances.

Results and discussion. This paper presents the results of preclinical tests of the obtained compounds.

Conclusion. Some compounds demonstrated high analgesic, anti-inflammatory and antipyretic activities and could be recommend for further study as perspective non-steroidal drugs.

Introduction. Recently, there has been a significant increase in fungal infections. The most common is vulvovaginal candidiasis, affecting millions of women worldwide. Resistance is formed to existing antifungal drugs, and they are not devoid of side effects. Previously, we have shown high antimicrobial activity of derivatives of 4-R-2-hydroxy-4-oxo-2-butenic acids. The creation of soft dosage forms based on them and the study of antifungal action is promising.

Aim. To develop experimental soft dosage forms based on one of the most active derivatives of 4-R-2-hydroxy-4-oxo-2-butenic acids and to evaluate the effect of the ointment composition of the ointment composition on the severity of antifungal action.

Materials and methods. As a pharmacologically active component, a hydrazone derivative of 4-phenyl-2-hydroxy-4-oxo-2-butenoic acid synthesized by us was used, which has pronounced antifungal activity. 8 experimental soft dosage forms based on hydrophobic and hydrophilic character have been developed. The active substance in a concentration of 1 % was introduced by standard technological methods according to the rules for the manufacture of dermatological ointments. To determine the antifungal activity of the ointments obtained, a three-nesting variant of the agar diffusion method was used. Comparison preparations are 2 % cream "Pimafucin" and 1 % cream "Clotrimazole".

Results and discussion. All the studied experimental soft dosage forms showed antifungal effects of varying degrees of severity. The greatest pharmacological effect was found in ointment compositions based on hydrophilic components of sodium-carboxymethylcellulose and polyethylene oxides. Their antifungal effect is comparable or exceeds the effect of comparison drugs.

Conclusion. 8 experimental soft dosage forms based on a derivative of 4-phenyl-2-hydroxy-4-oxo-2-butenic acid have been developed. Their antifungal activity has been studied. Two most active samples of experimental ointments were selected for further in-depth study.

Introduction. Natural biologically active substances (BAS) are distinguished by different polarity, which determines their physicochemical properties, including solubility. When using solvents of different polarity, it is possible to influence the spectrum of BAS extracted from plants, achieving their division into groups, and further achieving isolation in an individual form. Тhe aerial part of Linaria vulgaris Mill. (common toadflax) contains both lipophilic and hydrophilic substances. The herb L. vulgaris is widely used in folk medicine for treatment of angina, conjunctivitis, dermatomycosis, periodontitis and other diseases. Bacterial factors play an important role in the pathogenesis of these diseases.

Aim. To study the effect of solvents of different polarity on the component composition of extracted BAS and to study the antimicrobial activity of fractions from the herb L. vulgaris.

Materials and methods. The aerial part of L. vulgaris was collected at the flowering stage – at the beginning of fruiting stage in July 2021 in the Perm region. The fractions were obtained by sequential exhaustive liquid-liquid extraction of an alcoholic extract from the herb L. vulgaris with hexane, dichloromethane, and n-butanol. Detection of BAS was carried out by HPLC and planar chromatography on paper. Antimicrobial activity was studied against Escherichia coli, Staphylococcus aureus and Candida albicans.

Results and discussion. Using solvents of different polarity four fractions were obtained from the alcohol extract of L. vulgaris: hexane, dichloromethane, n-butanol and water. These fractions have differences in the composition of BAS. The number of polyphenolic substances in the fractions increases with increasing of solvent polarity: hexane (14), dichloromethane (55), butanol (61). The dichloromethane and n-butanol fractions have a similar composition, represented by polyphenolic compounds and iridoids. The main groups of compounds in these fractions are phenolic acids and flavonoids. Iridoids are found in trace amounts. In the hexane fraction, the smallest number of substances was found, iridoids are completely absent, and phenolic acids were found in trace amounts. The water fraction is characterized by the content of the entire BAS complex. The highest antibacterial activity against Escherichia coli and Staphylococcus aureus was found for the aqueous fraction, while the highest antifungal activity was found for the hexane and dichloromethane fractions.

Conclusion. Using solvents of different polarity, fractions containing a diverse set of BAS were obtained from the alcoholic extract of L. vulgaris. Fractions exhibiting different polarities from L. vulgaris have antimicrobial activity against Staphylococcus aureus and Escherichia coli, as well as against pathogenic fungi from the genus Candida.

Introduction. Leaves of peach (Persica vulgaris), containing a large amount of biologically active substances, including flavonoids, are considered as promising plant source for producing extraction preparations.

Aim. The purpose of the study: to establish the influence of phytotechnological parameters for efficiency of isolation of complex of biologically active substances from peach leaves.

Materials and methods. The object of the study was samples of dried leaves of the cultivated peach tree – Persica vulgaris Mill. (Rosaceae family) collected during the growing season (at the end of August). The main technological parameters of vegetable raw materials were studied: average particle size and fractional composition, volume characteristics of specific, volume and bulk mass, porosity, porosity and free volume of the raw material layer, аs well as the absorption coefficient of the extractant.

Results and discussion. The obtained values of the fractional composition and volume characteristics indicate the expediency of using the maceration method in plant raw materials extraction. Experimental studies were carried out to select optimal modes of extraction of flavonoids from peach leaves (extractant, extraction temperature, extraction duration, degree of raw material grinding, hydromodule), which ensure high output of BAS complex into extract.

Conclusion. The study presents the analysis of phytotechnological parameters of peach leaves, a rational extraction method is justified – maceration at heating with periodic stirring, and extraction conditions are determined; providing maximum yield of active substances: temperature – 70 °С in 40 min, extractant – alcohol, ethyl solution 70 %, degree of raw material grinding – 2 mm, raw material : extractant ratio (1 : 10).

Introduction. COVID-19 is recognized as the most significant pandemic of the modern era. Studies have shown the potential benefits of taking ascorbic acid in the complex treatment of this disease, especially in people with vitamin C deficiency. One of the most popular and affordable sources of ascorbic acid in the diet are rosehip fruits. The quality of water extracts from plant raw materials depends on a number of technological factors. The study of the influence of the technological regime of the production of water extraction from rosehip fruits on the release of ascorbic acid in the obtained dosage forms is relevant.

Aim. To obtain water extracts from rosehip fruits by various production modes and to study the effect of technological parameters on the content of ascorbic acid.

Materials and methods. The object of the study was rosehip fruits in bundles and water extracts based on them, obtained in the 6 different ways. Pharmacopoeial techniques, manufacturers' recommendations, as well as thermos infusion with and without preheating of the thermos flask were used. For quantitative determination of the ascorbic acid in the obtained aqueous extracts, we used the pharmacopoeia method (titration with 2,6-dichlorophenolindophenolate sodium).

Results and discussion. The lowest content of ascorbic acid was noted in the decoction according to the pharmacopoeia method. High levels of ascorbic acid content were noted in the variants of thermos infusion of rosehip fruits.

Conclusion. We have obtained extemporal water extracts of rosehip fruits by the 6 different extraction modes. According to the content of ascorbic acid, the most effective method of obtaining extemporal water extraction of rosehip fruits is a six-hour thermos infusion with preheating of the thermos flask. The largest amount of ascorbic acid is released during a six-hour thermos infusion. In the twelve-hour thermos infusions, a decrease in the amount of ascorbic acid was found. It was found that preheating the thermos flask leads to an increase in the yield of ascorbic acid in aqueous extraction by 25 %.

Introduction. According to the World Health Organization, the number of patients with diseases of the nervous system in the world is increasing every year. The use of phytopreparations is a promising direction of pharmacotherapy; preparations from medicinal plant materials have a number of advantages in the treatment of chronic diseases.

Aim. Qualitative analysis and quantitative determination of the main groups of biologically active substances collected from medicinal plant materials.

Materials and methods. As an object of study, we used a collection of medicinal plant materials developed at the Department of Pharmaceutical Technology of the PSFA together with the Department of Pharmacognosy. Quantitative determination of biologically active substances of the collection was carried out by spectrophotometric method [Jenway PortLab 511 UV spectrophotometer PortLab Int., UK)] and by visual titration.

Results and discussion. In this work, a qualitative analysis and quantitative determination of the content of flavonoids, phenolic compounds, sesquiterpenic acids and ascorbic acid was carried out, and the water absorption coefficient of the collection was determined.

Conclusion. As a result of the work, the content of flavonoids, phenolic compounds, sesquiterpenic acids and ascorbic acid in the developed collection was confirmed, their amount was determined, which directly affects the pharmacological effect of the collection.

Introduction. For new synthesized pharmacologically active compounds, already at the stage of standardization, it is necessary to develop methods for determining their quality indicators, normalized by a pharmacopoeial article for pharmaceutical substances. One of these indicators is the residual organic solvents, for the analysis of which chromatographic methods are suitable, for example, gas-liquid chromatography.

Aim. To develop conditions for the determination of residual organic solvents - acetic acid in a new pharmacologically active compound (substance of silver salt 4-[4-(acetylaminosulfonyl)phenyl]-6-(4-bromophenyl)-5-(2-nitrophenyl)-3,5-dihydropyrrolo[3,4-c]pyrazol-3-one), to validate the developed method.

Materials and methods. The substance of the silver salt 4-[4-(acetylaminosulfonyl)phenyl]-6-(4-bromophenyl)-5-(2-nitrophenyl)-3,5-dihydropyrrolo[3,4-c]pyrazole-3-one, synthesized at the Perm State Pharmaceutical Academy. The study was carried out by the gas chromatographic method (gas-liquid chromatograph Chromatec-Crystal 5000, JSC SDO «Chromatec», Russia).

Results and discussion. This paper reflects the results of the choice of gas chromatographic conditions for determining the residual organic solvent (acetic acid) in the substance, these conditions are evaluated according to the validation indicators required for analytical methods.

Conclusion. A procedure has been developed for determining the residual organic solvent in the substance of the silver salt 4-[4-(acetylaminosulfonyl)phenyl]-6-(4-bromophenyl)-5-(2-nitrophenyl)-3,5-dihydropyrrolo[3,4-c]pyrazole-3-one, the methodology was validated.

Introduction. Currently, there is much tension around the issue of increasing the efficiency of use of forest resources. One of these resources are scotch pine cones, which remain at the felling areas. Polysaccharides of scotch pine cones have a significant sorption activity; however, it remains unclear does the month, when raw materials were collected, affect the sorption activity.

Aim. The research of the content, sorption activity and molecular weight of water-soluble polysaccharides of scotch pine cones in different seasons of the year.

Materials and methods. Water-soluble polysaccharide complex (WSPC) of scotch pine cones was obtained with a method based on the well-known scheme for the carbohydrates separation according to Bailey et al. WSPC was obtained from the samples of scotch pine cones collected from July till March. Determination of the content of scots pine cones WSPC was spectrophotometrically carried out, with the modified Draywood anthrone-sulfurous method. The sorption activity of polysaccharides was determined by the methylene blue. The molecular weight of polysaccharides was identified by the viscosimetric method.

Results and discussion. The content of WSPC in scotch pine cones from July till March was identified. The highest yield of WSPC was registered in winter (3.24 ± 0.31 %), and the lowest in summer (0.46 ± 0.01 %). The sorption activity of scotch pine cones WSPC in terms of methylene blue from July till March was researched in vitro. It was found that WSPC has the highest sorption activity in October (230.69 ± 4.18 %) and November (243.30 ± 9.43 %). The WSPC sorption activity is above the activity of standard medications: absorbent carbon (230.9 ± 2.34 mg/g) and colloidal silicon dioxide ("Рolisorb MP") (211.5 ± 1.87 mg/g). The average molecular weight of scotch pine cones WSPC from July till March was determined. The average molecular weight of WSPC is in the range from 6 872,27 to 21 598,06. The dependence of the scotch pine cones WSPC sorption activity on the molecular weight was registered.

Conclusion. The water-soluble polysaccharide complex of scotch pine cones, obtained at different seasons, has different sorption activity, which depends on a polysaccharide molecular weight. The highest content and sorption activity of scotch pine cones WSPC matches with the period of wood production, which stipulates a practical use of cones and directions for future research.

Introduction. Alchemilla herb is proposed for introduction into pharmaceutical practice, for obtaining extracts with various pharmacological activity. To expand, resource base of Alchemilla it has been proposed to use a high biomass cultivated plant – Alchemilla mollis (Buuser) Rothm. In terms of qualitative and quantitative characteristics of the chemical composition Alchemilla mollis herb is comparable to the samples of raw materials of wild-growing Alchemilla. The presence of chemotaxonomic features necessitates the preparation of regulatory documentation for the introduction of this plant as a source of medicinal raw materials.

Aim. Development of a methodology for assessing the main group of biologically active substances and the quantitative determination of flavonoids in Alchemilla mollis herb.

Materials and methods. As objects of study, we used Alchemilla mollis herb harvested from plants cultivated in the Perm Krai. The chromatographic parameters of raw material authenticity were determined by thin layer chromatography (TLC). To develop the parameters for the quantitative determination of flavonoids in Alchemilla mollis herb, a modification of the method proposed for Alchemilla herb was carried out.

Results and discussion. During chromatographic study of Alchemilla mollis herb were identified cinaroside, rutin, and quercetin. Cynaroside was referred to the marker substances. Ethyl acetate : acetic acid (85 : 15) was chosen as the optimal chromatographic system. A modification and validation of the method for the quantitative determination of flavonoids in Alchemilla herb was carried out. The change of the extractant, particle size, time and frequency of extraction for sample preparation and the optimal use of cynaroside as a standard substance are substantiated. The optimal conditions for the reaction of complex formation with aluminum chloride are established.

Conclusion. To determine the authenticity of Alchemilla mollis herb, it was proposed to use the identification of cynaroside by TLC. The modified method for the quantitative determination of flavonoids in terms of cynaroside for the Alchemilla mollis herb, reproducible, correct and can be used for standardization. When testing the methodology on samples of raw materials harvested in the Perm region, a range of values for the content of flavonoids was 3.14–4.84 %, with an average level of variability.

Introduction. Due to the high prevalence and social significance of fungal infections, the search for new antifungal drugs is an actual direction t of modern pharmacology. One of the important components of preclinical microbiological studies is the culture media used in the process of a experiment.

Aim. To validate the use Sabouraud liquid medium as an alternative to RPMI 1640 medium to optimize the experimental conditions for the determination of antifungal activity of new compounds by the microserial dilution method.

Materials and methods. The micromethod of two-fold serial dilutions to study the antifungal activity of new molecules was used. Antifungal activity was studied against the reference test strain Candida albicans NCTC 885-653. The evaluation of the validation parameters was carried out according to the principles set forth in the General Pharmacopoeia Monograph.1.1.0021.18 «Validation of microbiological methods». A new compound from the group of 4-(het)aryl-2,4-dioxobutanoic acid amide derivatives was used for test the validated method.

Results and discussion. Results were obtained that meet the acceptance criteria for the studied validation parameters – trueness, precision, linearity, robustness and quantitation limit. The possibility of using Sabouraud's medium for the determination of antifungal activity was shown on the example of a new compound of the group of 4-(het)aryl-2,4-dioxobutanoic acid amide derivatives.

Conclusion. The tested alternative liquid Sabouraud medium can be recommended for use in determining the antifungal activity of the newly synthesized compounds with the microdilutions method because the proven its better growth properties for the investigated yeast strain and the convergence of the results of determining antifungal activity using alternative and reference media.

Introduction. The features of the chemical composition and the identified pharmacological activities of substances from fresh raw materials of the Alchemilla vulgaris allow us to predict the prospects for the use of juice from the herb Alchemilla vulgaris in medical practice. The creation of drugs based on juices from fresh herb Alchemilla involves the development of methods for their standardization.

Aim. To determine the methods of qualitative analysis for the identification and quantitative assessment of the main group of biologically active substances in Alchemilla vulgaris juice.

Materials and methods. The herb Alchemilla vulgaris for juice production was harvested during the flowering period in various habitats. The qualitative composition of the phenolic compounds of the juice was studied by paper chromatography and thin layer chromatography (TLC). The quantitative determination procedure was developed and validated on an SF-2000 spectrophotometer.

Results and discussion. Paper chromatography (CP) in the juice revealed derivatives of cinnamic and phenolcarboxylic acids, a group of flavonoids with a predominance of flavones and flavonols, rutin was identified among the dominant ones. The TLC in the butanol : acetic acid : water system (4 : 1 : 2), we achieved optimal separation of substances and identified rutin, which was proposed as the main substance in juice standardization. Correspondence of the configuration of the differential spectrum of the complex of cuff juice flavonoids with aluminum chloride to the spectrum of a similar complex of rutin SS and the results of TLC give grounds to use rutin as a standard. The best option when choosing an aliquot for quantitative determination of reliable results showed the use of 0.2 ml of juice. The content of flavonoids in the studied juice samples ranged from 2.15 ± 0.24 % to 7.34 ± 0.16 %.

Conclusion. TLC in the butanol-acetic acid-water system (4 : 1 : 2) can be used to authenticate the juice from the herb Alchemilla vulgaris. The parameters of the method of quantitative determination are developed taking into account the variation in the ratio of the water component and the dry residue in the juice. The method is valid and can be used to standardize juice from the herb Alchemilla vulgaris. The taxation of Alchemilla vulgaris juice samples showed the variability of the content of flavonoids in the juice depending on the growing conditions.

Introduction. The defeat of hard tissues of the tooth, accompanied by inflammatory processes, remains today an urgent medical and social problem for the population. Inflammatory processes cause acute pain and often lead to loss of teeth, which causes significant damage to the aesthetic and functional state of the dental system. Despite the large number of drugs created to date, methods for their use, the search and testing of new drugs for the prevention and treatment of diseases of the oral cavity does not lose its relevance and relevance in practical healthcare.

Aim. The purpose of this study was to study the anti-inflammatory activity of new dental dosage forms with Acyzol.

Materials and methods. Serial samples of gels and films with an active pharmaceutical substance – acyzol bis-(1-vinylimidazole)zincdiacetate (ФС 000286 191211.2011, LLC "Makiz-Pharma", Russia, 101218, shelf life 3 years) were used for the study; basic and gel-forming components – Na-KMTs C75 (TU 2231-002-50277563-2000, LLC "Chemical Products Base "Yugreaktiv", Russia, 151119, shelf life 3 years), glycerol (FS.2.2.0006.15 "Glycerin", JSC "Kupavnareaktiv", Russia, 082019, shelf life 3 years), purified water (FS.2.2.0020.18 "Purified water"), nipagin (LLC "Alfa-Veta.com", Russia, 092018, shelf life 3 years), nipazol (LLC "ECOCHEM-INNOVATION", Russia, 071518, shelf life 3 years). The studies were carried out on a model of carrageenan edema during external application of the studied dosage forms of Acyzol, modified taking into account the specifics of the dosage forms.

Results and discussion. An acute inflammatory reaction was induced by subplantar injection of 0.1 ml of a 1 % solution of carrageenin into the hind paw of a rat. An increase in the volume of the foot, indicating the development of edema, was assessed oncometrically before and 3 hours after the administration of the phlogogenic agent. The studied objects in the amount of 0.3 g were applied to the skin of the foot 0.5 hours before the introduction of carrageenan. Statistical processing was carried out according to Student's method using Microsoft Office Excel 2010 Professional software. Based on the results obtained, the effect of inflammation inhibition was determined as a percentage of the control level. The presence of anti-inflammatory action was judged by the severity of inhibition of the inflammatory response. If this indicator was more than 30 %, the result was taken into account as positive.

Conclusion. It has been established that the films and the gel have an anti-inflammatory effect, which was found in the model of carrageenan edema. The results obtained indicate the feasibility of further pharmacological studies and make it possible to recommend the gel and films as an effective tool for the prevention and treatment of oral diseases.

Introduction. Strawberry garden leaf extract dry (strawberry extract) is one of the potential substances for obtaining safe medicines for the treatment of diseases of the urinary tract, as it has diuretic and anti–inflammatory activity. The study of chronic toxicity is a mandatory step in the preclinical assessment of the safety of a new pharmacological substance.

Aim. Preclinical studies of the chronic toxicity of the substance – strawberry extract.

Materials and methods. The object of the study was strawberry extract obtained at JSC "Biohimmash". The study of the chronic toxicity of strawberry extract with prolonged administration to rats was carried out in the Laboratory of Medicinal Toxicology of the All-Russian Research Institute of Medicinal and Aromatic Plants in accordance with the "Guidelines for Experimental (Preclinical) Study of new pharmacological Substances" [1]. Laboratory animals were divided into three groups of 15 rats each: group I – control (water); group II – strawberry extract at a dose of 72 mg/kg; group III – strawberry extract – 720 mg/kg.

Results and discussion. As a result of a 3-month experiment, it was found that strawberry extract with intragastric administration does not cause the death of animals and does not have a general toxic effect. Also, strawberry extract with intragastric application shows a stable diuretic effect and its preservation during a three-month experiment.

Conclusion. Thus, the chronic toxicity of strawberry extract was studied. It was found that strawberry extract does not have a general toxic effect. The conducted research shows the prospects for further research on the development and production of medicines from strawberry leaves with dry extract, which have diuretic and anti-inflammatory activity.

Introduction. One of the widely used specific anti-HER₂ (human epidermal growth factor receptor 2) MAb drugs is trastuzumab. Trastuzumab is highly effective for malignant HER₂ hyperexpression reduction, which results in HER₂ oncogenicity decrease. As any other biotherapeutics trastuzumab can cause immunological adverse reactions, e.g. immunogenicity or anti-drug antibodies (ADAs) production.

Aim. The aim of this study was to develop and validate the analytical method for anti-trastuzumab antibodies determination in human blood serum.

Materials and methods. The semi-quantitative anti-trastuzumab antibody determination was carried out by the ELISA method combined with ACE technique, using spectrophotometric detection in the visible range of the spectrum.

Results and discussion. The developed method was validated for cut point, selectivity, sensitivity, "hook" effect, drug tolerance, precision and stability (short-term and long-term). To decrease the background noise from non-specific binding of sera components, the minimum required dilution value was determined at 10 % serum. The calculated values for screening cut point (normalization factor) and confirmatory cut point were 0.004 and 34.59 %, respectively. The sensitivity of the developed method was estimated at 99.5 ng/mL of anti-trastuzumab antibodies.

Conclusion. The obtained results allow us to use the developed ACE ELISA method for the determination of anti-trastuzumab antibodies in human serum during trastuzumab safety clinical trials.

Introduction. Destruction is one of the stages of the circulation of medicines. Special importance is attached to this stage in relation to drugs related to narcotic drugs and psychotropic substances. The activities of pharmacy and medical organizations in relation to the turnover of these funds are strictly regulated.

Aim. The purpose of the study was to study the procedure for the destruction of narcotic drugs and psychotropic substances included in Lists II and III of the List, as a stage of the circulation of medicines, to identify trends in the appointment of individual drugs for pain relief based on the generalization of archival data of the commission on destruction established on the basis of the Perm State Pharmaceutical Academy.

Materials and methods. Archival materials of the destruction commission for 2012–2021 were used in the execution of the work. Each archive folder for a certain month of the year included the following documents: an order for the commission on destruction and appendices, a set of documents and acts of destruction for each institution that provided medicines. Statistical and empirical methods were used, such as observation, description, study, generalization and grouping, comparison, proof.

Results and discussion. Data on prescribing drugs to cancer patients and data on drugs submitted for destruction correlate. Therefore, the range and quantity of medicines transferred for destruction by medical institutions allows us to see trends in their appointment and use in medical practice.

Conclusion. Optimization of activities related to the turnover of controlled substances can be ensured by building a clear algorithm of actions in a medical organization for each type of work and services specified in the license, including the type of work – destruction. The procedure for the destruction of narcotic and psychotropic drugs, which is accompanied by verification of accompanying documents and objects at the meetings of the commission, allows monitoring the use and accounting of drugs in medical institutions.

Introduction. New requirements for the registration of generic drugs after the entry of the Russian Federation into the Eurasian Economic Union (EAEU) and the signing of the Agreement on Common Principles and Rules for the Circulation of Medicinal Products identified a number of problems and opportunities that specialists in drug registration and working with regulatory authorities. The presented prospects for drug registration predetermine the list of tasks for the reorganization of the work of the department for work with regulatory authorities and the need to improve the competence of the employees of the manufacturers in order to carry out effective work.

Aim. Assessing critical steps in the generic drug registration process to improve the efficiency and organization of the Regulatory Affairs department.

Materials and methods. The materials of the study were available publications in peer-reviewed journals on thematic queries compiled according to the keywords of the chosen subject, official websites, regulatory legal acts regulating the procedure for registering drugs in the Russian Federation, the EAEU and foreign countries.

Results and discussion. A brief overview of regulatory issues on drug registration according to the requirements of the Eurasian Economic Union is presented. The critical stages of the drug registration process and the tasks that need to be solved in order to ensure the effective work of the department for working with regulatory authorities in the implementation of drug registration processes in the Russian Federation, the EAEU and other countries were identified. The role of professional qualifications of specialists involved in the preparation of the registration dossier and the processes of registration of medicines is indicated.

Conclusion. Changes in the legal regulation of the registration process and the imperfection of the requirements for specialists who carry out the procedures for preparing the registration dossier determine the need to develop organizational technologies and measures at the organization level aimed at standardizing all processes and forming professional specialized competencies of personnel.

Introduction. The key role in the organization of the pharmacovigilance system is played by the Marketing Authorization Holder (MAH), who monitors the safety and effectiveness at all stages of the life cycle of drugs, the need for which is determined by regulatory documents in the field of pharmacovigilance. The possibility of ensuring the required quality of the processes and the results obtained in the pharmacovigilance system of the MAH is directly related to the availability of a sufficient number of competent, qualified and trained personnel in the units that closely interact in the pharmacovigilance system of the MAH, which necessitates the formation of appropriate competencies for the implementation of procedures provided for when identifying changes in the safety profile of drugs. An integral part of the formation of competencies of employees and departments involved in the pharmacovigilance system of the MAH is training according to a specially developed program and evaluation of its effectiveness.

Aim. Substantiation of the formation of professionally specialized competencies and training of employees in the pharmacovigilance system of the MAH.

Materials and methods. The research materials were the results of the works of domestic scientists, data from their own research and regulatory legal acts regulating pharmacovigilance in the Russian Federation, the EAEU. Methods of sociological, logical analysis, and interactive learning were used as research methods.

Results and discussion. The necessity has been established and the professionally specialized competencies of managers and specialists of the MAH in the pharmacovigilance system have been formed, for the mastery of which an educational program has been developed and training has been conducted. Information and methodological support of personnel has been introduced.

Conclusion. In the course of the conducted research, it was found that training is an integral part of the organization of an employee's independent workflow. In order to achieve high-quality performance of processes and tasks related to pharmacovigilance, it is necessary to have a sufficient number of competent and trained personnel in the MAH. In order to update the acquired knowledge on pharmacovigilance, it is advisable to carry out intra-corporate training with a certain frequency.