Introduction. The issue of the sufficiency of natural resources of medicinal plants is currently becoming more and more acute. This is the reason for investigating the possibility of using invasive plants as sources of biologically active substances. Xanthium strumarium L. is a plant of the Asteraceae family, weed plant that is widespread almost all over the globe and has a multicomponent composition. Its use in the treatment of various pathologies is actively covered in scientific literature. The problem of using Common Cocklebur in the context of modern evidence-based medicine is becoming increasingly important.

Text. This article examines the chemical composition of common cocklebur based on studies published from 2005 to 2022. The composition of the essential oil as one of the main components is described in detail, and the comparison of the essential oil component composition of various chemotypes of cocklebur collected in different regions of the world is considered. Data on the composition of flavonoids, phenylpropanoids and steroids, alkaloids, fatty oils, resins, polysaccharides, amino acids, vitamins, glycosides and other compounds is considered. The structures of the main chemical components characteristic of the common cocklebur are given. The article presents data on experimentally confirmed types of biological activity. The experience of using cocklebur extracts in studies of antibacterial, antifunginal, scolicidal and antitrypanosomal activities is considered. In addition, information is provided on experimentally confirmed types of biological activity: antidiabetic, antitumor, anti-inflammatory, antioxidant and analgesic.

Conclusion. Based on the literature date, Xanthium strumarium L. can be considered not only as an invasive and polluting species that has actively spread almost all over the globe, but also as a potential medicinal plant with a rich chemical composition.

Introduction. Influenza type A is a socially significant infectious disease. Viral variability, mutations and reassortment make vaccination difficult. New drugs for specific therapy need to be developed because resistance to the existing drugs has appeared. A number of plant extracts have antiviral activity against the influenza type A virus, research is relevant in this area. The development of a species is also relevant, which has both specific antiviral activity and affects the symptom complex accompanying this disease.

Aim. To develop a medicinal herbal collection for specific and symptomatic treatment of influenza type A.

Materials and methods. There were considered 14 pharmacopoeial types of medicinal plant raw materials and 3 herbal compositions based on them. The studies of biologically active substances in raw materials were carried out according to the methods of the State Pharmacopoeia of Russian Federation, 15th edition. Determination of antiviral activity was carried out on Madin-Darby canine kidney cells (MDCK) culture using the hemagglutination reaction.

Results and discussion. There were studied the quantitative content of the main groups of biologically active substances (polysaccharides, tannins, flavonoids and ascorbic acid) in 3 variants of herbal compositions (collection No.No. 1, 2 and 3) and decoctions based on them. The variant of the herbal composition with the maximum content of biologically active substances was established. Antiviral activity against the influenza A virus of two herbal compositions was demonstrated.

Conclusion. The composition of the medicinal herbal collection is proposed, which is promising for complex therapy of influenza. The antiviral effect against the influenza virus type A has been proven.

Introduction. Biological medicines produced using recombinant DNA technology play an important role in the international pharmaceutical market. Currently, bacterial and mammalian expression systems are widely used to produce recombinant proteins, monoclonal antibodies, and vaccines. To maintain the quality and stability of inoculation, cell banks are generated.

Text. The general recommendations for cell bank development are outlined in the ICH Q5 guidelines. In the Russian Federation, similar requirements are specified in Decision No. 89 of the Council of the Eurasian Economic Commission "On approval of the Rules for assessments of biological medicines in the EAEU". Based on these requirements, one- or two-level cell banks should be established. Initially, a Master cell bank (MCB) is generated from a well-characterized single-cell bacterial colony according to high-quality standards. Subsequently, a Working cell bank (WCB) is created from one or several well-characterized MCB cryovials. As a result, the number of parameters required for WCB characterization can be reduced. The identity, purity, and stability of the cell bank should be determined. Requirements for cell bank characterization are detailed in official guidelines. An identity test is used to confirm the cell line or strain identification, which is a critical step to prevent cross-contamination and ensure the correct cell line in manufacturing processes. The absence of bacterial, fungal, or other types of contamination is demonstrated through purity testing. The sterility test is a key component, ensuring that a pure cell is used. The stability test demonstrates the genetic stability of the cells, including the preservation of genetic characteristics and the monitoring of harmful mutations during cultivation processes. Comprehensive data on the cell bank history, development, and characterization should be provided during its transfer.

Conclusion. This research presents the general concept of microbial cell bank development, characterization, and transfer based on bacterial expression systems.

Introduction. Purification of gas streams plays an important role in many industries in the field of environmental engineering. When implementing such measures, cyclones are often used – devices for cleaning gas streams from fine particles. In the pharmaceutical industry solving such problems requires the use of compact, highly efficient devices, for the development and study of which CFD-modelling methods have recently been increasingly used. The paper presents a comparison of the results of CFD-modelling of the gas purification process in a direct-flow cyclone of a new design and the capture efficiency in this apparatus obtained as a result of experimental studies.

Aim. Comparison of the results of numerical modelling of the gas purification process in two configurations of a direct-flow cyclone of a new design with the experimental results.

Materials and methods. The FlowVision software package was used for numerical CFD-modelling of the separation process in the studied device. The motion of the discrete phase – particles – was described using the Lagrangian particle model. Rosin-Rummler distribution with a minimum diameter of 15 microns, a median of 40 microns, and a maximum of 120 microns was used to distribute the particles by size. The experiments were carried out on an experimental setup, the main part of which was a direct-flow cyclone, a centrifugal fan and a screw doser. Technical talc was used as a model material, the dispersed particle distribution of which was determined by laser diffraction on a SALD-2300 particle analyzer (Shimadzu, Japan).

Results and discussion. The CFD-model of the device allowed us to determine the gas velocity field, flow trajectories and particle capture efficiency in the studied configurations of a direct-flow cyclone. Based on the information about the gas velocity field and flow trajectories, conclusions were made about the most effective 4 design solutions. Comparison of the numerical simulation results and the experimental results showed good convergence.

Conclusion. The developed design of the direct-flow cyclone showed good efficiency of fine particle capture. Numerical CFD-modelling allowed us to determine design features that negatively affect the efficiency and to optimize the design of the device. Good convergence of the model and experimental results confirms the possibility of using CFD-programmes for accurate modelling of technological processes and determining their parameters.

Introduction. The extremely unfavorable physical, chemical and functional properties of diosmin, a component of a number of popular phleboprotective drugs, cause an increased therapeutic dosage of the active pharmaceutical ingredient (API) in the dosage form and complicate the manufacturing process. In order to improve the characteristics of API, a technology of solid dispersion systems (SDS) creation by hot melt extrusion (HME) has been proposed. Particular importance in the context of current approach is attached to the selection of an effective polymer matrix.

Aim. The selection and justification of using a polymer carrier from the polyvinylpyrrolidone group for creating diosmin solid dispersions by hot melt extrusion.

Materials and methods. Object of study: diosmin (powder micronized substance, Chengdu Runde Pharmaceutical Co., Ltd., China). As candidates for the development of solid dispersions with a model ratio of API to carrier of 1 : 99, two related hydrophilic polymers were selected: a copolymer of polyvinylpyrrolidone with vinyl acetate in a ratio of 60 : 40 (PVPVA) – VIVAPHARM® PVP/VA 64 (JRS PHARMA GmbH & Co. KG, Germany), and polyvinylpyrrolidone brand Kollidon® K17 PF (BASF, USA). The thermal properties of the API and polymer carrier were characterized using synchronous thermal analysis. Diosmin SDS were obtained using a HAAKE™ MiniCTW twin-screw extruder (Thermo Fisher Scientific, Germany). The quantitative content of diosmin in the solid dispersions was determined by HPLC. To assess the effect of the extrusion process on the sample characteristics, the functional properties of API and milled SDS were compared. In particular, the thermal and structural characteristics were studied using differential scanning calorimetry and FTIR spectroscopy, respectively.

Results and discussion. Kollidon® K17 is not effective in binary diosmin solid dispersions due to the increased viscosity of the melt, the risk of forming a heterogeneous system, and the potential degradation of the samples' functional properties relative to the pure micronized API. Taking into account the specifics of the extrusion process, as well as the results of the thermal, structural, and functional characteristics analysis of SDS, it was concluded that copolymer of polyvinylpyrrolidone with vinyl acetate is the most effective. This polymer matrix enables more uniform dispersion and fusion with diosmin, along with a tendency towards possible amorphization of the API, and thus – the possibility of solubility properties improvement.

Conclusion. The utilization of a copolymer of polyvinylpyrrolidone with vinyl acetate improves the unfavorable characteristics of micronized diosmin, which will eventually eliminate deviations during the manufacturing process of solid dosage forms by reducing the risks of dust formation and mechanical losses, as well as ensuring uniform dosing.

Introduction. The development of nanotechnology has led to the creation of complex drug delivery systems: liposomes, dendrimers, inorganic nanoparticles, cellular systems, and polymer nanoparticles. All these systems require an integrated approach to quality control. This review examines the key attributes of quality control, including physico-chemical and chemical analysis methods, as well as current regulatory requirements.

Text. Drug delivery systems represent promising technologies aimed at improving the safety and effectiveness of pharmacotherapy. The variety of components and complexity of the structure create a number of difficulties in developing approaches to quality control of new media. Existing physical and physico-chemical analysis methods are actively used to determine the morphological characteristics of carriers, the physical characteristics of their membrane, and to confirm the structure of substrates and the final particle. However, the lack of a number of standardized approaches, in particular, for determining the zeta potential of a particle membrane, remains a serious challenge for a number of researchers and regulatory authorities.

Conclusion. This review provides a systematic description of the approaches to quality control of delivery systems and their components that currently exist. The variety of media analysis methods makes it possible to fully assess the quality of media, but in the future it is necessary to harmonize existing international standards with Russian standards, which minimizes the risks associated with the use of media in the targeted delivery of medicines.

Introduction. Information on the seasonal variability of essential oils has a key decision in determining the seasons of harvesting: the variation of component composition should be minimal, and the concentration ranges should correspond to those established in the regulatory documentation, while the maximum possible yield of essential oil should be observed. Rosemary grows in the south of the Russian Federation (the Republic of Crimea, the Caucasus) and the chromatographic profile of its essential oil is not fixed in the regulatory documentation, and in the Russian-language scientific literature there are no studies of seasonal variations in the component composition of essential oil, despite the fact that in the Republic of Dagestan rosemary blooms almost year-round.

Aim. Study of seasonal variations in the essential oil of the rosemary of Dagestan origin.

Materials and methods. Estimation of essential oil content was carried out in accordance with the requirements of the European Pharmacopoeia 11th edition by hydrodistillation using a Clevenger apparatus. Gas chromatographic analysis was carried out using a gas chromatograph Crystal 5000.2 equipped with a flame ionization detector, separation was carried out on fixed phase columns of different polarity: HP-5MS UI and DB-WAX. The components were identified by comparing the calculated linear retention indices obtained on two columns of different polarity with reference values.

Results and discussion. The content of essential oil of rosemary in the plant raw material ranged from 2.06 to 2.24 %. Statistical analysis revealed no significant differences between the results obtained during the experiment. According to the results of gas chromatographic was able to establish α-pinene chemotype of essential oil of Dagestan origin. In the samples of essential oils 30 compounds were identified, constituting at least 95 % of their composition. When interpreting the results of statistical processing of the content of components depending on the date of collection of raw materials, significant differences were noted for the majority of major components.

Conclusion. The study was the first to describe the component composition of essential oil of rosemary (Salvia rosmarinus Spenn., seu Rosmarinus officinalis L.) of Dagestan origin. Detected during the study statistically significant differences in the content of components depending on the date of collection of plant raw materials can be used for chromatographic profiling of essential oil of rosemary of Dagestan origin. This approach will allow not only to reflect the geographical variability of the component composition, but also seasonal. 

Introduction. Phytosomes containing a complex of plant components with phospholipids are highly soluble in lipid and aqueous media, overcome skin barriers well, and enhance the bioavailability of substances with low solubility. For phytoecdysteroids, substances with a wide range of pharmacological actions in the course of biopharmaceutical research, the prospects of creating nanoscale liposomal forms have been shown.

Aim. Development of conditions for obtaining phytosomes with ecdysteroids of Serratulae coronatae L. and assessment of their quality.

Materials and methods. The amount of ecdysteroids isolated from Serratulae coronatae L., the main of which is 20-hydroxyecdysone (at least 75 %). Large multilayer vesicles were obtained by forming a lipid film with further homogenization in an ultrasonic bath. The particle size, polydispersity index, zeta potential (ζ-potential) were determined on the device Zetasizer Nano ZS (Malvern Instruments Ltd., United Kingdom). The degree of inclusion of the active component was estimated by HPLC.

Results and discussion. The composition has been developed and technological stages have been proposed to obtain phytosomes (small single-layer vesicles) with a diameter of 130–170 nm and an IP ≤ 0.3. The formation of hydrogen bonds in the structure of phytosomes with the main ecdysteroid of Cimicifuga racemosa, 20-hydroxyecdysone, has been confirmed using NMR spectrometry. The degree of encapsulation of Echinops ritro ecdysteroids in phytosomes was 88 and 84 % after one year of storage.

Conclusion. The technology of phytosomes with ecdysteroids of the Serratulae coronatae L. has been developed. The stability of the resulting phytosomal complex indicates the possibility of creating soft dosage forms based on it.

Introduction. Esomeprazole is a proton pump inhibitor widely used in the treatment of acid-related diseases of the upper gastrointestinal tract. Upon inhalation exposure, it is classified as a substance of the highest hazard class, which requires monitoring its concentration in the workplace air at pharmaceutical enterprises. Despite the availability of methods for the quantitative analysis of esomeprazole in various matrices in the scientific literature, there are currently no methods for analyzing this substance in workplace or industrial air.

Aim. To develop a method for the quantitative determination of esomeprazole magnesium trihydrate in workplace air using HPLC-MS/MS.

Materials and methods. Air samples were collected using membrane filters with a diameter of 25 mm at a flow rate of 5,0 L/min. The analysis was performed using reference standards of esomeprazole magnesium trihydrate and carbamazepine. Chromatographic separation was carried out on a C18 column (2,5 μm, 100 × 4,6 mm). Detection was performed using a mass-selective detector in positive electrospray ionization mode by multiple reaction monitoring. MRM transitions were: 346,1 → 198,1 m/z for esomeprazole and 237,1 → 194,1 m/z for carbamazepine.

Results and discussion. The method was validated according to the following parameters: suitability of the chromatographic system (the number of theoretical plates, N, for esomeprazole is at least 13170 and for carbamazepine, at least 5617), the asymmetry factor (A_s) for both substances does not exceed 1,36 and 1,41, respectively; limit of detection: 17 ng/mL; lower limit of quantification: 50 ng/mL; specificity (the response of interfering peaks for esomeprazole at most 1,2 % and for carbamazepine at most 0,25 %); linearity in the range of 50–5000 ng/mL (determination coefficient (R₂) of at least 0,9995, accuracy from 92,8 to 106,1 %, and relative standard deviation (RSD, %) at most 4,2 %); intralaboratory accuracy (from 99,6 to 102,2 %) and interlaboratory accuracy (from 100,5 to 101,6 %); intralaboratory precision (RSD at most 4,3 %) and interlaboratory precision (RSD at most 5,8 %). All validation parameters met the acceptance criteria. The stability of esomeprazole on filters was confirmed for up to three months of storage.

Conclusion. The development and implementation of the method enabled quantitative analysis of esomeprazole in workplace air and the assessment of the safety of the production process in accordance with hygienic requirements.

Introduction. Among all types, type 2 diabetes mellitus (T2DM) shows the most rapidly growing prevalence, and has the greatest number of complications including peripheral polyneuropathy, which is aggravated with age. In view of this, the search for effective agents for the correction of T2DM-associated polyneuropathy is highly relevant.

Aim. To study the effects of course administration (1 month) of glycyrrhizinic acid (GA) (20 mg/kg/d) on neuromotor function in female leptin-resistant diabetic db/db mice of different ages using stimulation electroneuromyography (ENMG).

Materials and methods. The study was conducted in female C57Bl/Ks-db⁺/⁺m (db/db) mice weighing 40–48 g, aged 2 months (n = 15) or 6 months (n = 10) that were randomized into 4 groups: 1) control (C) (2 months (C2): n = 7; 6 months (C6): n = 5); 2) GA-treated (20 mg/kg/d p/o × 1 month) (2 months (GA2): n = 8; 6 months (GA6): n = 5). Following 1 month of treatment, an ENMG study of m. gastrocnemius and m. biceps brachii electrical activity was conducted using the following protocols: single stimulus presentation, electrical stimulation-induced fatigue, and repetitive stimulation. Additionally, nerve conduction velocity (NCV) was measured for n. ischiadicus.

Results and discussion. In the GA2 group, compound muscle action potential (CMAP) peak amplitude and area in the biceps were 37.4 % (p < 0.05) and 44.5 % (p < 0.01) lower than respective control values, which may be related to possible hypokalemia induced by long-term GA use, including that resulting from 11β-hydroxysteroid dehydrogenase-2 inhibition. The relatively smaller reduction of the same parameters observed in the GA6 group may be explained by lower basal enzyme activity in aged animals. CMAP durations in the biceps were 21.7 % lower in the C6 group vs. C2 (p < 0.05), while threshold current values were 48.4 and 50.4 % higher in both GA2 and C6 groups vs. C2 (p < 0.01 for both). The decrease in CMAP duration and increase in threshold currents possibly reflects age-associated changes including muscle fiber and motor unit loss.

Conclusion. GA (20 mg/kg/day × 1 months) in young adult (2 months) female leptin-resistant mice reduced single stimulus-induced CMAP amplitude and area in the biceps muscle. The compound had no effect on sciatic NCV and post-ESIF recovery rates of the gastrocnemius and biceps in both 2 month- and 6 month-old mice.

Introduction. The vesicular fraction of human mesenchymal stem/stromal cells (EV MSCs) secretome can be considered as a pharmaceutical substance for the biological drug development to treat fibrotic diseases. Biological drugs quality control requires standard tests using simple validable methods. Additionally, it is necessary to assess specific activity using relevant models based on specific cellular targets and mechanisms of action.

Aim. Development of cell models for specific activity assessment of the biological drug from human EV MSCs for the fibrotic diseases treatment.

Materials and methods. We proposed two in vitro models to evaluate specific activity: the first one is primary human dermal fibroblast (HDF) cell lines induced differentiation model and the second one is polarization of macrophages derived from human peripheral blood monocytes.

Results and discussion. Transforming growth factor (TGFβ-1) treatment of HDF increased the level of the main myofibroblasts marker – alpha-smooth muscle actin (αSMA) within 96 hours. The simultaneous action of TGFβ-1 and EV-MSCs significantly decreased αSMA level compared to TGFβ-1-stimulated fibroblasts. Macrophages polarization towards M1-type with LPS/IFNγ combination resulted in increased IL-6, IL-12p35, TNFα genes expression after both 4 and 24 hours. The EV-MSCs addition to M1-type decreased the gene expression of proinflammatory cytokines IL-6, IL-12p35, TNFα in 24 hours.

Conclusion. We developed two in vitro models to assess specific activity of antifibrotic drug based on human EV-MSCs. In the first model value of specific activity is at least 2.5-fold decrease of αSMA level in TGFβ-1-stimulated HDF, comparing to non-treated control. In the second model the value is at least two-fold decrease in the level of IL-12p35, IL-6, TNFα expression in M1 macrophages, compared to non-treated M1 macrophages.

Introduction. Analysis of animal coat and skin coloration can be used as an auxiliary method for assessment of various conditions and processes that are accompanied by changes in coloration, intensity, proportion of coat colors or areas covered by fur, undercoat, and skin. Performing coloration analysis in preclinical studies requires new straightforward, fast, and easily standardizable digital methods that yield reproducible data suitable for statistical processing.

Aim. In this work, we aimed to develop and test a novel algorithm for quantitative analysis of coat and skin coloration in laboratory animals using R programming language.

Materials and methods. To analyse fur coloration, we used digital photographs of female guinea pigs, one bicolor and one calico, that were taken under artificial lighting against a plain contrasting background. Analysis of fur and skin area proportion was carried out re-using photographs of a male mouse with depilation alopecia model, which were obtained during a previously published preclinical study. Colorimetric image analysis was performed by hierarchical k-means color clustering in RGB space and cluster area calculation using the recolorize v0.2.0 function package for R v4.2.3 with RStudio v2025.05.0.

Results and discussion. The algorithm for colorimetric analysis included 3 steps: 1) preprocessing images and masking the background; 2) hierarchical color clustering and reclustering; 3) calculating absolute and relative color cluster areas. Using the described algorithm, we found the color area proportion to be 46.1 % agouti vs. 53.9 % yellow for the bicolor guinea pig, and 9.1 % red vs. 19.6 % white vs. 71.3 % black, for the calico one. In the male mouse subjected to depilation, we characterized the dynamics of proportion between areas of hairless skin and skin with regrown hair across a 28 day-long period. We found a decrease in relative of hairless skin area between the 0^th, 9^th, and 17^th days post-depilation from 8.7 to 7.4 % and to 0.0 %, respectively (p < 0.05 for 17^th day vs. 0^th and 9^th).

Сonclusion. In this work, we described and tested on model photographs an algorithm for analysis of coat and skin coloration using hierarchical color clustering. The algorithm does not require the use of specialized software, is fast and straightforward, and can be employed for batch image processing to obtain quantitative data for further statistical analysis.

Introduction. The high doses of vitamin D lead to undesirable side effects such as hypercalcemia. Paricalcitol (PC) is a biologically active synthetic substance that selectively binds to intracellular vitamin D receptors and does not cause hypercalcemia. The effect of this drug on metabolic pathways, parathyroid hormone secretion, asthma and liver fibrosis is known, which confirms its wide clinical potential. However, only a few publications have been devoted to the effect of different doses of PC on the state of liver cells, which are the most important site of its metabolism.

Aim. To study the effect of intraperitoneal administration of different doses of paricalcitol on the degree of activation of vitamin D receptors and to conduct a morphological assessment of the state of liver tissue in mice.

Materials and methods. The experiment involved male BALB/c mice without external pathological signs, weighing 16– 18 g and aged 4–6 weeks, which were divided into 4 groups. Healthy animals of the control group received 100 µl of saline solution intraperitoneally. Animals from the groups 2, 3, and 4 received PC intraperitoneally at the doses of 25 ng/mouse, 50 ng/mouse, and 100 ng/mouse, respectively on the days 1, 2, 4, and 7. Sacrifice was performed on the 10th or 21st day after the onset of the experiment. Histological assessment of liver tissues of animals removed from the experiment on day 10 was performed according to generally accepted histological methods. Immunohistochemical examination was performed automatically in a Bond™- maX immunohistostainer (Leica, Germany). Primary rabbit polyclonal antibodies to the vitamin D receptor were used.

Results and discussion. The introduction of PC in different doses consistently increased the total number of liver cells expressing VDR, mainly due to immune cells. An increase in the percentage of intensely stained non-parenchymatous cells (++++ and +++) was observed by the 21st day of the experiment and amounted to 56.0 % in subgroup 2.2, 3.2 – 46.6 % and 4.2 – 48.0 %, in the control group this value was 39.5 %. The liver tissue structure closest to the control was observed in animals that received PC at a dose of 25 ng/mouse. In the groups of mice where the animals received PC at doses of 50 ng/mouse and 100 ng/mouse, certain morphological changes were noted, mainly of a dystrophic and discirculatory nature, which reflected the toxic effect of these doses of PC on the metabolism of hepatocytes.

Conclusion. The administration of different doses of PC leads to an increase in VDR expression mainly in non-parenchymatous liver cells that perform immune functions. VDR expression in hepatocytes of all subgroups increased by the 10th day of observation and decreased by the 21st day, which was probably due to the death of these cells. Microscopic examination showed that the use of PC in healthy mice leads to certain dose-dependent changes in the liver, the least toxic dose of PC is 25 ng/mouse.