Annals of Mechnikov's Institute 2020 N 1




C. (P.)

Editorial Board








Riboflavin in photodynamic inactivation of pathogens and photodynamic therapy

Pogorelaya M, Martynov A, Romanova E.,

Mechnikov institute of microbiology and immunology

Riboflavin, besides its key role in providing cellular metabolism in humans and animals, is used as a compound of antimicrobial photodynamic therapy (aPDT) owing to its photosensitizing capability. PDT is a promising approach for the photoinactivation of pathogens in blood and blood derivatives. It has been reported, that the advantage of antimicrobial photodynamic therapy is that there are no resistant strains to it. Flavins are photoreducible and photon-induced excitation of them in the ultraviolet-blue (UV-blue) spectral band can lead to formation of either singlet oxygen via energy transfer to environmental oxygen, or hydrogen peroxide and derivatives via radicalisation altogether termed reactive oxygen species (ROS) and used hereafter. Exactly the ROS production property of riboflavin is used for antiviral and antibacterial disinfection; for strengthening the corneal tissue in photorefractive surgery by the ROS-induced collagen cross-linking. Several studies reveal the antimicrobial photodynamic potential of riboflavin irradiated with the ultraviolet-blue and with visible light against methicillin resistant Staphylococcus aureus, Staphylococcus epidermidis, enterohemorrhagic Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii and Bacillus subtilis in vitro. It was shown, that riboflavin/UV-A and allowed effectiveness against such fungal pathogens as Candida albicans, Candida parapsilosis, Fusarium sp, and A. fumigatusas which may cause infection keratomycosis.  The photoilluminated riboflavin significantly reduced the activity of superoxide dismutase (SOD) and reduced the level of cellular antioxidant metabolite - glutathione (GSH). Along with that the specific activity of glutathione S-transferase (GST) - which is involved in detoxification process - was increased significantly in cells exposed to photoilluminated riboflavin. Riboflavin, illuminated by UVA or visible light, has also been developed as a nucleic acid-binding agent to be used for photoinactivation of such nucleic acid-containing pathogens in plasma, platelets, and RBCs as viruses. Several studies have revealed the effectiveness of reduction in some viruses infectivity, including human immunodeficiency virus 1 (HIV-1), bovine viral diarrhea virus (BVDV), hepatitis B virus (HCV), pseudorabies virus. Thus, the riboflavin+UVB system has found their application in pathogen reduction technology Mirasol Pathogen Reduction Technology (PRT) system. Riboflavin has been thought to be a promising antitumoral agent in photodynamic therapy, though the further application of the method was limited by the unclear molecular mechanism. Several studies reveal that of PDT-mediated cytotoxicity occur in three ways: apoptotic, necrotic and autophagy-associated cell death.  Some findings, show that certain PDT techniques acting via inducing of apoptotic cell death that is highly immunogenic and can stimulate antitumor immunity. Thus, we can conclude that, the riboflavin+UVB system is suitable for photoinactivation of bacteria, fungi and viruses and has a potential in antitumor treatment strategies. Further studies will reveal more and more aspects of riboflavin capabilities.

Keywords: riboflavin, photodynamic, antimicrobial, antiviral, UVA, UVB



Experimental works



Development of technology of plant species for complex mastopathy therapy
S. S., Vyshnevska L. I.
At present, the range of medicines for the treatment of mastopathy is represented, for the most part, by foreign manufacturers, which are currently not economically available to the general population of Ukraine. Structure of the range of medicines used in mastopathy therapy, by country of origin. Almost 44% of the assortment is domestic products. That is, these drugs provide both physical (availability at the place of sale of the drug) and economic affordability (the price of the drug suits the consumer). Given the need to implement the principles of import substitution, the development of original domestic preparations based on medicinal herbs for the treatment of mastopathy is relevant. The use of standardized drugs based on medicinal plant raw materials (MPRM) will allow more comprehensive coverage of all pathogenetic mastopathy pathways, reduce the dosage of synthetic chemotherapy drugs, and pay more attention to the quality of women's rehabilitation while maintaining their health and reproductive function. The importance of the above has led to the development of a new drug in the form of collection for use in gynaecology, which includes various types of MPRM, capable of effectively acting on all the etiological and pathogenic links of mastopathy. The pharmaceutical market of Ukraine has no analogues of a standardized herbal remedy for complex treatment of mastopathy, but the available ingredients have long been used in folk medicine. Material & methods. Based on the results of pharmaco-technological studies, a technological scheme of obtaining non-dosed and dosed species for use in the complex treatment of mastopathy was developed. Results & discussion. The main stages of the process of collecting and the critical parameters that are monitored at each stage are identified. The technology of collecting in different types of packing is described: in aluminium foil packs, plastic bags and Doy-packs and filter bags.Vegetable raw materials used for the preparation of the drug must be subject to input control for compliance with regulatory requirements. Mastonorm species technology includes the following stages of the production process: preparation of medicinal plant raw materials, production of Mastonorm species, weighting, packaging and marking of the Mastonorm species. For dispensing, there is a step of filling, packing and labelling Mastormorm species into filter bags. Conclusion. The technology of Mastonorm species was developed. The technological scheme of obtaining Mastonorm species in industrial conditions was developed. The technological industrial regulation of production of the Mastonorm species in different types of packing has been developed: plastic bag enclosed in cardboard packs; aluminium foil packs; Doy-packs and filter packages of 1.5 g 20.

Keywords: technology, medicinal plant species, mastopathy.




Quantitative determination of microbiom in the destination content the gut in rats

Bukina Yu.V.

Introduction. The gut microbiome significantly affects the functioning of the body: it participates in the protection of the body against pathogenic microorganisms, in the processes of metabolism, inhibition of inflammatory responses, in the formation of innate and adaptive immune response in the intestinal mucosa. One of the reasons for changing the microbiota is the use of antibiotics. Therefore, the processes of interaction of antibiotics, Salmonella enteritidis and Salmonella typhimurium with representatives of normal intestinal microflora are of particular interest. Materials and methods. The quantitative and qualitative composition of the wall microbiota in rats by bacteriological method, the statistical analysis of data using the program StatSoft Statistica v12 were conducted. Results & discussion. With the introduction of vancomycin and S. enteritidis, S. typhimurium in groups II, III, IV there was a decrease in E. coli quantitative content by 10, 7 and 110 times, respectively (p≤0.05). The number of P. aeruginosa decreased significantly only in the third group (p≤0.05). The number of representatives of Bacteroides spp. significantly decreased by several thousand times (group II) and by 70 and 87 times (groups III and IV) (p≤0.05). The content of E. faecalis and E. faecium decreased by 861,6 and several thousand times (groups II, III, IV) (p≤0.05). The number of Proteus spp. significantly decreased in group II by 27 times and increased rapidly in group IV (p≤0.05). Group III showed a sharp decrease in the content of representatives of Enterobacter spp. and Klebsiella spp. in 847 and 150 times, and in group II there is an increase in their number by 7 and 46 times, respectively (p≤0.05). The number of Staphylococcus spp. decreased by 9.8 times only in II group. The quantitative content of Clostridium spp. decreased by several thousand times (group II) and by 5.5 times (group IV) (p≤0.05). The number of Lactobacillus spp. decreased by several thousand times (group II). The number of representatives of Bifidobacterium spp. significantly decreased by 10.9 times and by several thousand times (groups III, IV). The quantitative content of Peptostreptococcus anaerobius decreased significantly in all three study groups (p≤0.05). The content of Salmonella spp. increased in group II by 49 times and significant increase was observed in groups III and IV (p≤0.05). The introduction of salmonella, against the background of vancomycin pre-treatment, causes a dramatic change in the composition of the microbiota in groups V and VI, namely: an increase in the number of E. coli 65 and 105 times, a significant increase in the content of P. aeruginosa in the V group, and in the VI, 3 times. Also, in these groups there is a decrease in the number of Bacteroides spp. 9 and 10 times (p≤0.05). The content of E. faecalis and E. faecium decreased significantly only in the fifth group (p≤0.05). The number of Proteus spp. decreases 17 times in group V and also a significant decrease was observed in group VI (p≤0.05). A sharp increase in the content of representatives of Enterobacter spp. and Klebsiella spp. was observed in the V and VI groups (p≤0.05). However, representatives of Peptostreptococcus anaerobius in V and VI groups decreased 20 and 9 times, respectively (p≤0.05). The number of Salmonella spp. decreased only in group V 7 times (p≤0,05). With the introduction of experimental animals B. fragilis treated with S. enteritidis, S. typhimurium on the background of vancomycin pre-treatment, a significant decrease in the level of E. coli in group VII, and in VIII - by 538 times (p≤0.05). The number of P. aeruginosa in groups VII and VIII decreased significantly and the number of representatives of Bacteroides spp. naturally increases (p≤0.05). The content of Lactobacillus spp. decrease by 10.3 times only in VI group. The content of E. faecalis and E. faecium increased by 10 and 19 times in the seventh and eighth groups respectively, and the number of Proteus spp. decreases only in group VII 322 times (p ≤0.05). Also, in VII and VIII groups there is a sharp decrease in the content of representatives of Enterobacter spp. and Klebsiella spp. (p≤0.05). The level of representatives of Peptostreptococcus anaerobius and Lactobacillus spp. increased significantly 7, 12 times and several thousand and 40 times (groups VII and VIII, respectively) (p≤0.05). The number of S. enteritidis and S. typhimurium in the VII and VIII groups decreased intensively (p≤0.05). Conclusions. The introduction of B. fragilis can be used in the treatment of inflammatory bowel diseases or diseases with impaired barrier function of the intestine.

Keywords: parietal microflora, microbiome, vancomycin, salmonella, bacteroids.




The influence of polyols on the bacteriotropic properties of the Lactobacillus reuteri cell-free superants

Knysh O.V., Martynov A.V., Voyda Yu.V., Babych Ye.M.

Introduction. Precursor directed biosynthesis is one of the promising approaches to finding new antimicrobial agents and creating next-generation probiotics. L. reuteri is capable to convert triatomic polyol glycerol into reuterine, a broad-spectrum antimicrobial substance. There are no data on the use of other polyols as precursors. The aim of the research was to investigate the effect of cell-free supernatants obtained by culturing L. reuteri DSM 17938 in its own disintegrate, supplemented with polyols (xylitol, sorbitol, mannitol and glycerol & glucose) on the daily biomass growth of opportunistic microorganisms. Material & methods. Reference strains Staphylococcus aureus ATCC 25923; Escherichia coli A 25922 and Pseudomonas aeruginosa clinical isolate were used as a test cultures. The effect of the lactobacillus supernatant on the daily biomass growth of the test cultures was investigated by spectrophotometry using a 96-well polystyrene microtiter plates and a LisaScanEM spectrophotometer (ErbaLachemas.r.o., Czech Republic). The final concentration of supernatants in the incubation medium was 30%, and the final concentration of bacterial cells was ~106 CFU/ml. Inhibition (II) or stimulation (SI) indices of the daily biomass growth of test cultures by formula were calculated. Results & discussion. Supplementation of culture medium with glycerol & glucose during L. reuteri cultivation resulted in the S. aureus (II = 70.7%), Escherichia coli (II = 72.2%) and P. aeruginosa (II = 74.7%) daily biomass growth inhibition. As a result of L. reuteri cultivation in its own disintegrate supplemented with mannitol, the supernatant acquired growth-promoting properties with respect to S. aureus (SI = 45.5%), E. coli (SI = 19.1%) and P. aeruginosa (SI = 19, 9%). The supernatant obtained after L. reuteri cultivation in disintegrate supplemented with sorbitol had no significant effect on the S. aureus and Escherichia coli daily biomass growth, but significantly stimulated the growth of P. aeruginosa (SI = 29.4%). The supernatant of L. reuteri, cultured in disintegrate supplemented with xylitol had no effect on staphylococcus growth, inhibited of E. coli (II = 16.5%) growth and increased of P. aeruginosa (SI = 19.1%) daily biomass growth. The data obtained for glycerol, the introduction of which into the culture medium of L. reuteri led to the appearance of inhibitory activity of the supernatant against all test cultures, were expected. They coincide with the results of studies by other authors and are associated with the ability of this type of lactobacilli to convert glycerol into a broad-spectrum antimicrobial substance reuterin. The results of the study confirm that xylitol, sorbitol and mannitol do not undergo fermentation with the formation of acidic end products during the cultivation of L. reuteri. These polyols remain either unchanged or undergo slight modification in the composition of the supernatant and have different effects on the daily biomass growth of test cultures. Conclusion. The results of the study showed that the use of xylitol, sorbitol and mannitol as precursors, and L. reuteri DSM 17938 as a biotransformer system in the development of new antimicrobials using a precursor-directed biosynthesis strategy is ineffective. They also confirmed that the supernatant obtained after cultivation of L. reuteri DSM 17938 in its own disintegrate supplemented with glycerol & glucose, has a pronounced inhibitory activity against the investigated opportunistic microorganisms.

Keywords: polyols, Lactobacillus reuteri, cell-free, supernats



Critical parameters of the production process of oromucosal drug for the treatment of helminthiases in children

Semchenko K. V., Vyshnevska L. I.

Introduction. Troches are very popular in children due to their high compliance, pleasing organoleptic characteristics and easiness of administration. Nevertheless, the expanding range of drugs in this dosage form still lack anthelmintic products.  In order to introduce the new anthelminthic drug in the form of chewable troches under the conditional name Albenpast, there were conducted the studies over selection the optimal gel-forming agent and flavorings as correctors of taste characteristics. The purpose of this work is to develop the technology of chewable troches under the conditional name Albenpast and to establish the critical points of the production process. Materials & methods. As the objects of research the pure substances (albendazole, gelatin, glycerol, purified water, glucose syrup, fructose, citric acid, fruit flavoring, food coloring) and samples of troches on their basis were used. The research methods used are reflected in the State pharmacopoeia of Ukraine. Results & discussion. Research was conducted against the chewable troches Albenpast to the composition of the components of which the patent is claimed. Compositions of troches 1 and 2 differ in the type of sweetness flavoring: 1 contains glucose syrup, 2 contains fructose. Composition 2 is offered for the use in children who need to control the level of glucose.  The production process offered includes 9 stages with critical points in 2, 3, 4, 5 and 7. Additionally, for each stage the possible types of quality control are described. The further quality control of the obtained by the offered technology samples of chewable troches showed their full correspondence with the requirements of SPhU. Conclusion. The technological process of production of chewable troches is offered and the technological scheme of their production is given. Critical parameters of the production process and their values are identified and described. The results of the quality evaluation of obtained chewable troches according to the main quality indicators in accordance with the requirements of SPhU are presented.

Keywords: oromucosal drug, production, helminthiases, children




Molecular dynamics study of the structural role of metal atoms in the urease active site

Lisnyak Yu. V., Martynov A. V.

Introduction. Urease is a representative of a small group of enzymes that can bind different alternative metals to execute the same catalytic function. The experimental X-ray studies conclude that a urease activity critically depends on the precise positions of amino acid ligands at a metallocenter, the bound solvent molecules and the type of metal, and very subtle changes of metallocenter structure can essentially influence the urease activity. Are these conclusions valid in the case of the urease structures in the solution? By molecular dynamics simulations, we studied these aspects for urease derivatives with alternative metals in solution under physiological pH and temperatures. Methods. Molecular dynamics (MD) simulations were carried out for the following systems: Ni-containing Sporosarcina pasteurii urease both native (PDB code 2ubp) and in complex with competitive inhibitor acetohydroxamic acid, AHA (PDB code 4ubp); Klebsiella aerogenes urease both Ni- and Mn-containing (PDB codes 1fwj and 1ef2, respectively); Fe-containing Helicobacter mustelae urease (PDB code 3qga) (table 1). As well, there was studied an apoenzyme of Ni-containing urease: the structure of the complex of competitive inhibitor AHA with Sporosarcina pasteurii urease (4ubp) from which there were removed Ni atoms. The systems studiedsubunits or its complex with competitive inhibitor) were placed in a cubic periodic cell filled with TIP3P water molecules. The simulation cell was 1 nm larger than the molecular system studied along all three axes. Na+ and Cl¯ counterions were added to neutralize the system and to reach ion mass fraction 0.9% NaCl. Before simulations the systems were energy-minimized. After a short steepest descent minimization, the the procedure continued by simulated annealing minimization.  AMBER14ipq force field was used. To treat long-range electrostatic interactions the Particle Mesh Ewald algorithm was used. The equations of the movement were integrated by 2.5 fs step. To speed up the calculations the non-bounded van der Waals and electrostatic forces were evaluated only each second step and added with the scaling factor 2.  The molecular dynamics simulations were run in NPT ensemble at pH 7.4 and two temperatures (298 K and 310 K).  Trajectories were computed for 50 ns, the data were saved each 25 ps. Models building, structure refinement, molecular dynamics simulations, and analysis as well as the result presentation by using molecular graphics were performed by using the molecular modeling program YASARA Structure. Results and discussion. After equilibration the RMSD values for different systems are close to each other and change insignificantly (except Fe-containing Helicobacter mustelae urease), evidencing that their global structure is quite stable and that no significant  conformational transformations occur within these systems, whereas H. mustelae urease structure revealed instability during the simulations. The presence of the competitive inhibitor in the active site did not change the Ni (1) and Ni (2) coordination numbers. There were observed no essential deformations of the geometry of the ions binding with the active site ligands as well. A similar situation was observed in the case of Mn-containing K. aerogenes urease too.  In the case of S. pasteurii urease apoenzyme, there were observed the insignificant shifts of the active site residues. The root mean square deviation of the residues of the active site of apoenzyme relative to holoenzyme was 0.65 Ǻ. In the absence of Ni ions in apoenzyme, the position of the inhibitor AHA within the active site is unstable and it gradually drifts and leaves the active site. For all ureases, the temperature increase from 298 K to 310 K had a little effect on the average distances metal-ligand. The temperature increase from 298 K to 310 K had an insignificant effect on the distances metal-water in the active site of the Ni-containing ureases S. pasteurii and K. aerogenes and a little influence on these distances in the Mn-containing K. aerogenes urease. The metallocentre structures in the Mn- and Ni-containing K. aerogenes ureases are very similar. Conclusions. There have been studied the structural role of the nickel ions in a urease active site, the influence of the temperature and the ion type on the structure of the urease active site. It have been shown that binding of the competitive inhibitor (acetohydroxamic acid, AHA) did not change the Ni ions coordination in the urease active site and  did not essentially effect the geometry of the active site near the nickel ions. The main factor of the inhibitor binding are the nickel ions. It have been shown that the active site structures of the Ni- and Mn-containing ureases Klebsiella aerogenes and Sporosarcina pasteurii are approximately identical. It have been shown that the metallocentre structure of these ureases are in general stable regardless of the urease source, the ion type and the temperature.

Keywords: urease metallocentre, Ni-, Mn- and Fe-containing urease, molecular dynamics.



Standardization of a method for identification of elecampane sesquiterpene lactones
Kotova E., Kotov S., Kotov A.
Introduction A wide use of elecampane, Inula helenium L. (Asteraceae), in both, folk and formal medicine, is explained by variety of its chemical composition. Rhizomes and roots of elecampane contain an essential oil, the content of which reaches 4%; the composition of the oil includes a mixture of sesquiterpene lactones. The main components of this mixture are alantolactone (0.5-2.0%), isoalantolactone (1.0-2.7%), and their hydrogenated derivatives: dihydroalantolactone, dihydroisoalantolactone, tetrahydroalantolactone, etc. These compounds seem to be responsible for pharmacological action of elecampane-based preparations. Herbal drug (HD) from elecampane is rhizomes and roots. There is no monograph on this type of HD in the State Pharmacopoeia of Ukraine (SPhU), therefore research related to its development is relevant. The mandatory identification test for HDs by the thin-layer chromatography (TLC) method in accordance with the requirements of SPhU is absent in the article GF XI "Rhizomes and roots of elecampane", therefore it is necessary to develop a procedure for identification of the main biological active substances (BAS) of elecampane by TLC-method. Materials and Methods. The rhizomes and roots of Inula helenium L. (Asteraceae) were obtained from various pharmaceutical enterprises of Ukraine during 2016-2018. The following equipment was used: Silica gel 60 F254 TLC plates (20x20 cm2, 0.25 mm), Merck (Germany); Ultrasonic bath SUPER RK100H Bandelin, (Germany); Glass vertical chamber; Automatic spraying device ChromaJet DS20. As standard substances have been used alantolactone, isoalantolactone and dihydroisoalantolactone (<95%) - pharmacopoeial reference standards of the State Pharmacopoeia of Ukraine. Results and discussion. A procedure for identification of elecampane by TLC method for the national monograph of the SPhU "Elecampane roots and rhizomes" has been developed.. The identification method is based on the ability of silver ions to react with unsaturated C-C bonds in the molecules of the isomers at the position of double bonds, which are alantolactone and isoalantolactone. The development of a procedure for identification was carried out in conjunction with its validation in accordance with the requirements of SphU according to the following scheme: 1) the choice of stationary phase (examination of plates with a thin layer of silica gel treated with 1, 3, 5, 7% (m/v) solutions of silver nitrate); 2) the choice of mobile phase (review of unified phases for chromatography of terpenoids); 3) the choice of concentration for markers-substances (study of 0.05, 0.1, 0.2% methanol solutions of alantolactone, iso-alantolactone, dihydroiso-alantolactone and SQTL mixture for preparation of the reference solution); 4) the choice of the method for test solution preparation (study of extraction of herbal material with methanol, followed by concentration of the extract to the ratio of HD-test solution 1: 2, 1: 5, 1: 8); the choice of application volume of the test solution ; 5) the choice of the detection method (review of unified reagents and/or solutions for derivatization of chromatograms). Following conditions for identification have been chosen: the test solutions of HD (1: 5 in methanol), standard solution CRS SPhU alantholactone and isoalantholactone (0.1% solutions in methanol), TLC plates with a thin layer of silica gel treated with 5% silver nitrate solution, a solvent system toluene-ethyl acetate (9: 1), detection is carried out after treatment the plate with anise aldehyde solution and followed by heating. Conclusion. A procedure for identification of elecampane by for the national monograph of the SPhU "Elecampane roots and rhizomes" has been developed. It allows to identify such biologically active substances of the elecampane, as sesquiterpene lactones, which are markers of this species The developed chromatographic conditions allow to reliably chromatographically identify HD of elecampane in the presence on chromatograms of 3 zones of lactones alantolactone, isoalantolactone and dihydroisoalantolactone.
Keywords. Elecampane roots and rhizomes, sesquiterpene lactones, monograph of the SPhU, TLC method, alantolactone, isoalantolactone and dihydroisoalantolactone.




Research of antimicrobic activity of foaming products samples with octopirox

Zaika S.V., Strilets O. P., Baranova I.I., Bezpala Yu. O., Martyniuk . V.

Introduction.  Seborrheic dermatitis (SD) - chronic recurrent skin disease, which is associated with increased cutaneous fatty secretion, change in its qualitative composition and is characterized by localization in the areas of accumulation of sebaceous glands on the scalp, face, upper torso. Therefore, the choice of tactics for the treatment of patients with SD depends on the degree of clinical manifestations, duration of the disease, information about the effectiveness of previously conducted therapy. Particular attention is paid to the choice of antifungal medicines in the treatment of SD. Traditionally, local remedies in the form of ointments or creams are used to treat SD of the scalp, they cause many inconveniences when used. In this respect, foaming products, in particular shampoos, which include active substances that have certain therapeutic potential regarding the main mechanisms of SD treatment, having self-regulating, anti-inflammatory, antifungal, antibacterial, reparative, moisturizing properties, etc. are very appropriate. One of the main factors in the development of this disease is the yeastlike fungus of Malassézia fúrfur genus (or Pityrósporum ovále), which is present in the skin of each person. Octopirox, which has strong fungicidal (antifungal) and antibacterial actions, was chosen among a number of modern products in this field. Therefore, the main purpose of our experiment was to study the antimicrobial activity of developed samples of foaming agents with octopirox to justify the rational concentration. Materials and methods. For this study, we produced a number of experimental samples of foaming bases with octopirox and α-lipoic acid at different concentrations: sample 1 -  foaming base; sample 2 foaming base +  α-lipoic acid; sample 3 foaming base + octopirox (0,25 %); sample 4 foaming base + octopirox (0,5 %); sample 5 foaming base + octopirox (0,75 %); sample 6 foaming base + octopirox (1,0 %). The antimicrobial activity of prototype gels was studied in vitro by diffusion in agar (wells method). This method is based on the ability of active substances to diffuse in the agar medium, which was previously inoculated by bacterial crops. The results of the studies make it possible to characterize both the antimicrobial activity of the samples and the release of antimicrobial substances from the base, because the growth inhibition zones of microorganisms are formed as a result of the diffusion of these substances into a dense nutrient medium. Results. Based on the experimental data, in the development of the foaming product composition with octopirox AFI concentration of 0.5% is optimal and further increase it to 0.75% (sample No. 5) and 1.0% (sample No. 6) is impractical. It should be noted that the studies showed that foaming samples had high antifungal activity and moderate effect on gram-negative bacteria, so in the development of the optimal composition of the tool and its long-term storage and use, it is necessary to consider the introduction of preservatives and conduct appropriate research.  Conclusion. Thus, the results of the experiments showed that the test samples No. 1 and No. 2 did not have any antimicrobial action pertaining to gram-positive, gram-negative bacterial cultures and antifungal activity. Samples No. 3, No. 4, No. 5 and No. 6 of the foaming product with octopirox at concentrations of 0.25%, 0.5%, 0.75% and 1.0% have a broad spectrum of antimicrobial action pertaining to gram-positive (Staphylococcus aureus ATSC 25293 and spore cultures of Bacillus subtilis ATSS 6633), gram-negative (Escherichia coli ATSS 25922 and Pseudomonas aeruginosa ATCC 27853) bacterial cultures, as well as in relation to the cultures of Candida albicans fungi ATSS 885-653 and Aspergillus niger fungus ATCC 16404. However, the experimental results showed that sample No 4 (octopirox concentration of 0.5%) was the most promising for further work on the development of antimicrobial activity of the foaming product.

Key words: seborrheic dermatitis, antimicrobial activity, octopirox, foaming product, product for men.