Annals of Mechnikov's Institute

Personalized approaches in phage therapy of multidrug-resistant infections

Vadym Poniatovskyi — 2024-12-05

The global spread of infections caused by multidrug-resistant microorganisms highlights the importance of discovering and developing new antimicrobial agents. Bacteriophages, including the strategy of their combined use with antibiotics, may serve as an additional element in the fight against antibiotic-resistant microorganisms. Bacteriophages have been used to treat infectious diseases since the early 20th century. However, the use of phage therapy today faces a number of challenges, primarily related to the limitations imposed by modern medical regulatory requirements and the insufficient development of effective therapeutic practices based on the principles of evidence-based medicine. This article provides an overview of current approaches to various therapeutic applications of bacteriophages

Investigation relationship between antimicrobial, antioxidant activity and biologically active compounds of blackberry (Rubus fruticocus L.) fresh fruit liquid extracts

Artem Marchenko — 2024-12-05

Introduction. The search for natural antibacterial agents has gained significant interest in recent years, driven by the growing concerns over antibiotic resistance and the desire for natural alternatives. Fresh blackberries, known for their rich nutritional profile and high antioxidant content, have attracted attention for their potential antibacterial properties. Understanding the antibacterial potential of blackberries could provide insights into their use in natural medicine and food preservation. Material and methods. The quantity of phenolic compounds, anthocyanins was determined by spectrophotometric method of analysis, whereas organic acids by alkalimetric method; antioxidant activity of obtained extracts was evaluated by potentiometric method, antimicrobial was determined by method of "well". Results and Discussion. Results demonstrates the highest amount of polyphenols, anthocyanins were 0.35±0.01, 0.29±0.02 in 96% ethanolic extract, respectively. The organic acids were dominated in aqueous and 60% EtOH extracts (0.84±0.02%). The most potent antioxidant property possessed 96% EtOH extract of blackberry fresh fruit. There is a high correlation between the content of polyphenols, antioxidant activity and inhibition of Bacillus subtillis, whereas antioxidant power highly depends on total polyphenols and anthocyanins. Conclusion. These findings show the great potential of blackberry extracts in the development and creation of new medicines with antimicrobial, antioxidant effects that are not inferior to the action of synthetic analogues.

Prospects for using the fruits of Viburnum opulus to obtain medicines of various directions of action

Olha Khvorost — 2024-12-05

Introduction. Viburnum opulus L. is a wild shrub, widely distributed in Europe, North Africa and North Asia. The fruits contain vitamin C, carotenoids, organic acids, iridoids, phenolic compounds, etc. BAC. But, despite the fact that the SPhU 2.4 contains the monograph "Viburnum fruits", the prevalence of the plant in Ukraine and a wide diverse spectrum of pharmacological activity, a medicinal product has not been created yet. Therefore, the aim of this work was conduct an analysis of the domestic pharmaceutical market of raw materials - fruits of Viburnum opulus, products based on them, and to offer several original substances from this type of raw material. Material & methods. The range of viburnum fruits on the domestic pharmaceutical market and products based on it was studied through content analysis of a number of Internet platforms. Fruits of viburnum for the development of the technology for obtaining funds were harvested during 2020-2022 in the Chuguyiv district of the Kharkiv region in the mass fruiting phase. The development of the technology for obtaining liquid and dense extracts was carried out according to generally accepted methods. Results & discussion. The domestic market contains the raw material fruits of viburnum of 42 domestic producers, products of the food industry (20 products), cosmetic industry (11 products) and 31 dietary supplements, of which 87% are domestically produced. In this regard, we have developed and standardized substances based on fruits of viburnum in the form of liquid and dense extracts, which are at the stage of preclinical research. The liquid extract from the fruits was obtained by maceration of the raw material with 50% ethanol for 48 hours, from which the technology for obtaining “Viburnikor” tablets with cardioprotective action was developed. The dense extract was obtained from fruits of viburnum by extraction with 90% ethanol. The significant content of organic, in particular, phenolcarboxylic acids and anthocyanin aglycones determines the antimicrobial and antioxidant effect, which further involves the creation of gels and sprays for the treatment of inflammatory processes of the oral cavity and skin. Conclusions. Considering the aspects of the biological action of fruits of viburnum, the breadth of their sale in Ukraine, the range of dietary supplements based on them in the domestic pharmaceutical industry, the creation of medicines with antimicrobial, anti-inflammatory, antioxidant, membrane-stabilizing action based on original liquid and dense extracts from fruits of viburnum is promising. Further introduction into the industrial production of pharmaceutical enterprises in Ukraine of tablets with liquid extract "Viburnikor" of cardioprotective action is relevant.

Morphological and anatomical study of underground organs of Syringa vulgaris l.

Andriy Popyk — 2024-12-05

Introduction. Common lilac (Syringa vulgaris L.) is one of the most widespread and favorite ornamental plants in the world, often used in landscape design. It belongs to the Oleaceae family, which includes 31 species and more than 1600 varieties. Representatives of the lilac genus are common in Southeastern Europe, Japan, China, the Himalayas, and Ukraine. Common lilac has a long history of use in traditional medicine in different countries. The bark, leaves, fruits, and flowers of the plant are known to have medicinal properties. In traditional Chinese medicine they are used as an analgesic, anti-inflammatory and stomachic agent, the fruits and bark of the plant are used as a tonic, and tincture of the leaves – for the treatment of malaria. Japanese traditional medicine uses the flowers and bark of the plant as a diuretic and tonic. Scientific evidence confirms the antioxidant, anti-inflammatory, antipyretic, immunomodulatory, antitumor and anti-allergic properties of common lilac raw materials. The bark of the plant is a natural source of syringine, which is a marker compound in the standardization of Eleutherococcus prickly pear drugs. However, the literature analysis shows that there is no information on a detailed study of the underground organs of common lilac. In order to expand the raw material base, we consider it expedient to study the underground organs of common lilac. The aim of the study was research the morphological and anatomical structure of the underground organs of common lilac growing in Ukraine. Materials and methods. The object of the study was roots and rhizomes of common lilac, which were harvested in the botanical garden of the NUPh. The experiment was conducted on 5 series of raw materials collected in the fall of 2023. Microdissections were prepared from dried soaked and freshly collected raw materials fixed in an ethanol-glycerin-water mixture (1:1:1) according to generally accepted methods. The preparations were examined under a LOMO Mikmed 1 light microscope at 60-400x magnification; the results were recorded using a SCIENCELAB 10.0 MPix Color CMOS digital camera. Results and discussion. The system of underground organs of common lilac depends on the age of the bush, the method of propagation (rhizomes are formed during vegetative propagation) and is somewhat divers in different varieties. Thus, in the first year, the system of the main root and hypocotyl (root neck) with adventitious roots develops. Subsequently, a mixed root system of the main and adventitious roots is formed, which later become dominant. Already from the second year, the bases of the main and lateral shoots of the bush are drawn into the soil by 2.5-5.0 cm. During the second growing season, horizontal stolon-like rhizomes rapidly grow from all the buds located in the cotyledon axils, lower stem leaves and adventitious hypocotyl buds. They are yellow-white, with brown scaly leaves, adventitious roots and dormant buds. After flowering begins, the development of rhizomes increases significantly. With age, the main root system dies off and the bush has only rhizomes and superficial adventitious roots of shoots. It is characteristic that old rhizomes differ little from roots in morphology. Their surface darkens and becomes woody, leaf scales disappear, buds are not visible, and a dense system of root taproots is formed along the entire length, which go deeper by about 40 cm. The roots are cylindrical, straight or slightly curved, curved, 10-15 mm thick. The surface is light brown, brownish. The cortex is scaly, sometimes flaky and exfoliating. At the break, the roots are light flesh-colored (ivory), fibrous-granular, with noticeable annual rings. The periderm crust is multilayered, the phelloderm is narrow, 2-3-layered. The largest area is occupied by wood with radiating arrangement of vessels and tracheids. The medullary rays are 1-3-row, cells with starch grains. In the bast, dense areas of bast fibers and sclereids alternate with arrays of conductive and basic tissues. Between the rings of thick- and thin-walled elements of the bast there are layers of large-cell parenchyma with large simple starch grains. The cambium is multi-rowed and clearly visible. Studies of cross-sections of thin and thickened rhizomes showed that the periderm gradually grows due to the activity of the phylogeny. Thus, at first the cortex is 3-4-layered, with slightly thickened lignified membranes, the phylloderm is 1-2-layered. The cortex of perennial, lignified rhizomes is multilayered, dense, cortical parenchyma is obliterated. The secondary bark is broad, consisting of several alternating belts of soft thin-walled and hard thick-walled bast. The hard cortex is represented by dense strands of narrow bast fibers with thickened lignified sheaths and large round or oval sclerites grouped in 2-4 or more. Their sheaths are significantly thickened, lignified, and permeated with slit-like pores. Core rays are primary, single, double or multiple rows, sinuous, cells narrow, with brownish contents. Cavities appear in the bark of perennial stems as a result of parenchyma obliteration. The wood is radiant, represented by medium-diameter porous vessels, ladder tracheids and libriform. The perimedullary zone of perennial rhizomes consists of cells containing a brownish secretion. The core parenchyma is loose, the cells are rounded, with more or less thickened porous membranes. The secondary cortex is broad, consisting of several alternating belts of soft thin-walled and hard thick-walled bast. The hard bast is represented by dense strands of narrow bast fibers with thickened lignified shells and large round or oval sclereids grouped in 2-4 or more. Their shells are significantly thickened, lignified, and permeated with slit-like pores. Core rays are primary, single, double or multi-row, sinuous, narrow cells with brownish contents. Cavities appear in the cortex of perennial rhizomes due to parenchyma obliteration. Wood is radiant, vessels of medium diameter, tracheids are ladder-shaped, wood fibers are significantly thickened. The parenchyma of the heartwood rays is brownish in color, forming single or multi-row strands. The perimedullary zone of rhizomes of all ages, and mostly perennial roots, consists of cells containing a brownish secretion. The core parenchyma is loose, the cells are rounded, with more or less thickened porous membranes. Conclusions. 1. The morphological characteristics of the roots and rhizomes of lilac were studied. 2. The anatomical structure of the underground organs of lilac was studied and the main diagnostic features of the studied raw materials were established. 3. The obtained results can be used for the development of quality control methods for roots and rhizomes of lilac.

Keywords: Syringa vulgaris L , roots and rhizomes.

Study of chronic toxicity of narrow-leaved lavender extracts: influence on functional status and laboratory indicators of rats

Olena Bogatyrova — 2024-12-05

Introduction. Despite the widespread use of chemotherapeutic drugs, medicinal plants continue to maintain the scientific interest of today's pharmacologists. In order to saturate the domestic pharmaceutical sector with affordable phytopreparations of a wide spectrum of action, scientists of the National Pharmaceutical University (postgraduate student Gurina V.O. under the supervision of Doctor of Pharmaceutical Sciences, Professor Georgiyants V.A.) obtained extracts of narrow-leaved lavender containing biologically active substances: terpenoids (linalool, linalyl acetate and traces of 1,8-cineole), flavonoids (hyperoside, isoquercitrin) and hydroxycinnamic acids (rosmarinic, chlorogenic). As a result of experimental microbiological tests, it was established that the herb of narrow-leaved lavender of Ukrainian origin is a promising and affordable source of potential antimicrobial active pharmaceutical ingredients. Also, based on the results of studying the acute toxicity of narrow-leaved lavender extracts when administered intragastrically to white mice, conclusions were drawn that allowed the studied test samples to be classified as class V of practically non-toxic substances (LD₅₀>5000 mg/kg). The aim of the work. Experimental study of the toxicological properties of extracts of L. angustifolia (chronic toxicity) to substantiate the safety of use in clinical practice. Materials and methods. The objects of the study were experimental test samples: No. 1 - extract of narrow-leaved lavender obtained by extraction with purified water; No. 2 - extract of narrow-leaved lavender obtained by extraction with a water-ethanol solution (40% ethanol); No. 3 - extract of narrow-leaved lavender obtained by extraction with a water-ethanol solution (70% ethanol). Test samples of narrow-leaved lavender were used at a dose of 100 mg/kg, which corresponds to 1/50 of the LD₅₀ of the experimental agents, which was determined at the previous stage of the study. Chronic toxicity studies of narrow-leaved lavender extracts were conducted on 48 white non-linear rats of both sexes with an initial weight of 170-190 g with daily intragastric administration for 90 days. In the collected urine, general properties (colour, transparency, pH, density), total protein content (by reaction with sulfosalicylic acid), glucose content (by glucose oxidase method) and urinary sediment were determined. Then, a complete laboratory blood test was performed using general scientific haematological methods and the following were determined: haemoglobin and erythrocyte content, colour index, leukocyte content, leukocyte formula, and erythrocyte sedimentation rate. Creatinine content (by reaction with picric acid) in blood and urine was determined. Endogenous creatinine clearance was calculated to assess the glomerular filtration rate. In the blood serum of rats, the urea content (diacetylmonooxime method), total protein (biuret method), glucose content (glucose oxidase method), ALT and AST activity (Reitman-Frankel method), bilirubin content (Jendrassik-Grof method), cholesterol content (modified Liebermann-Burchard method) were determined. The significance of differences between samples was assessed using the Kruskal-Wallis method and the Mann-Whitney test in comparison with the intact control group. Results and discussion. According to the results of experimental studies, it was found that intragastric administration of lavender test samples in selected doses throughout the entire observation period did not have a significant negative effect on the general condition, condition of the skin and mucous membranes and behaviour of rats. During the experiment, no case of animal mortality was registered. All indicators of the body weight of rats were within the physiological norm for this age group. On the 45th and 90th day of the study, no statistically significant effect of the extracts was registered relative to the intact group on the indicators of spontaneous daily diuresis, specific gravity and pH of the urine of animals. The use of narrow-leaved lavender test samples did not have a significant effect on the indicators of the level of glucosuria in rats of all experimental groups, while this indicator was not determined by generally accepted methods of quantitative and qualitative analysis, which is within the physiological norm. During the analysis of the urinary sediment of animals receiving narrow-leaved lavender extracts, no signs of urinary syndrome and pathophysiological changes in the ratios of formed elements were detected. The content of erythrocytes, leukocytes, epithelium, and cylinders was within the physiological norm, and at the level of intact animals, it was 0-3 in the field of view. With prolonged use of narrow-leaved lavender test samples, no statistically significant effect was observed on nitrogen metabolism and biochemical blood parameters in animals. Fluctuations in blood urea and creatinine were within the physiological norm. All studied parameters: glucose, total protein, cholesterol, bilirubin, AlAT and AsAT activity in the intact and experimental groups are within the range of normal values for rats and do not exceed the physiological norm. This indicates that lavender test samples in the studied doses with intragastric administration do not affect the parameters characterizing the functional state of the liver and kidneys of rats. During the study, no toxic effect was recorded on the parameters of peripheral blood of rats. In the leukocyte formula of rats of the experimental groups under the influence of chronic use of narrow-leaved lavender test samples, the percentage ratio of different forms of leukocytes also corresponded to intact animals and did not differ from the normal values. The only exception can be considered to be the increase in the content of rod-shaped neutrophils under the influence of test sample No. 2 as of day 90 of the study, which probably exceeds the intact level but, despite this, is within the physiological norm for rats. Conclusions. With chronic (90 days) intragastric administration, test samples of L. angustifolia at a dose of 100 mg/kg do not cause death in rats. It has been established that under conditions of chronic use, test samples of narrow-leaved lavender do not have a toxic effect on the general condition, behaviour and dynamics of body weight, do not cause significant differences in laboratory test parameters of urine and blood, and practically do not affect the functional state of the urinary and hepatobiliary systems of animals.

Codeines Medicine: ABC/VED Analysis, Effectiveness and Rationality of Application

Oleksandr Nevzghoda — 2024-12-05

Introduction. Pharmacoeconomic analysis is an important tool for evaluating the rational use of medicines, especially in conditions of limited funding. Codeine medicines are used to treat pain and cough, but their cost and share of total medicines costs can vary widely. The use of ABC and VED analyzes helps to estimate the costs and clinical importance of medicines, which allows to optimize the processes of their purchase and use. The aim. The purpose of this study was to conduct a pharmacoeconomic analysis of ABC/VED of medicines with codeine to assess their effectiveness and rationality of use. Materials and methods. The study was conducted using ABC analysis methods to determine the cost of medicines and their specific weight in total costs. To assess the clinical importance of medicines, VED analysis was used, which divided medicines into the categories of vital, necessary and secondary. Results. According to the results of the ABC analysis, the 8 most expensive medicines, which make up 80.53% of the total costs, are included in category A. Medicines of category B accounted for 15.02% of costs, and category C — 4.44%. The VED analysis showed that no medicines fall into the essential (V) category, and the majority of medicines fall into the essential (E) and secondary (D) categories, with the largest share of spending on category D medicines. Conclusions. The conducted pharmacoeconomic analysis revealed that the main costs fall on medicines that are not vitally necessary, but have a high specific weight in the total costs. The results of the study allow us to draw a conclusion about the need to optimize the use of codeine-containing medicines to reduce the financial burden on the health care system.

Keywords: pharmacoeconomic analysis, ABC analysis, VED analysis, medicines with codeine, costs, rationality of use, optimization.

Determination of numerical indicators of collection for prevention and treatment of diseases of the musculoskole system

Tetiana Oproshanska — 2024-12-05

Diseases of musculoskeletal system are some of the most common in the world which are leading to partial or complete limitation of the patient's mobility. Treatment of such diseases requires comprehensive and long-term therapy which includes nonsteroidal anti-inflammatory drugs, glucocorticosteroids, analgesics and muscle relaxants are used in therapy to reduce pain. But these drugs have strong side effects with prolonged use. In this aspect, an alternative to synthetic drugs are phytopreparations which have anti-inflammatory, analgesic, antimicrobial, antioxidant, diuretic effects and normalize metabolism. Taking into account the above mentioned and based on the results of our previous studies of plant raw materials, we developed the composition of the original collection “Opornofit” for the prevention and treatment of diseases of the musculoskeletal system with anti-inflammatory and membrane-stabilizing effects. The aim of the work is to determine the following numerical indicators of some series of collection “Opornofit”: loss on drying, total ash, quantitative content of total polyphenols, total hydroxycinnamic acids, total organic acids, and mineral composition. To establish the lower and upper limits of numerical indicators and elements, the study was conducted on 3 series of collections. Plant raw materials were harvested in the summer and autumn of 2022 in Kharkiv region and Vinnytsia region. Loss on drying, quantitative content of total polyphenols, total hydroxycinnamic acids and total organic acids were determined according to monographs of State Pharmacopoeia of Ukraine. Total ash was determined according to monographs of Europian Pharmacopoea 11^th edition. Elemental analysis was carried out using the atomic emission spectrographic method with photographic registration on the DFS-8 device. The loss on drying is not more than 12.5 % and the total ash is not more than 7.0 %. The quantitative content of total organic acids in terms of malic acid was not less than 2.2±0.11 %, the total hydroxycinnamic acids in terms of chlorogenic acid was not less than 1.5±0.05 %, the total polyphenols in terms of pyrogallol was not less than 4.4±0.17 %. The elemental composition of the 3 series of collection was the same and represented by at least 19 mineral compounds. In the 3 collection series, the following pattern of macroelements content is observed: K>Ca>Mg. Depending on the collection series, the quantitative content of macroelements K, Ca and Mg and the microelement P fluctuates by 1.3 times. The content of the microelement Si is less variable in the 3 series of collection and fluctuates by 1.1 times. The fluctuation of the content of Fe is 1.4 times, Al – 1.5 times, Mn – 1.8 times and Cu – 1.3 times. The content of the macroelement Na and the microelement Zn is comparable. The quantitative content of elements such as Pb, Mo, Ni, Co <0.03 and Cd, As, Hg <0.01. The content of heavy metals is within permissible limits. Conclusions. For the first time, a number of numerical indicators of the series of the original collection “Opornofit” were determined with the establishment, respectively, of the lower (content of total organic acids, total hydroxycinnamic acids and total polyphenols) and upper (loss on drying and total ash) limits of values. The mineral composition of 3 series of collection was also established. These data will be used in the development of the relevant sections of the project of methods for quality control of the collection “Opornofit”.

Keywords: collection, numerical indicators, elemental composition

Study of the chemical composition of the thick extract of snapdragon herb

Sofia Ilyna — 2024-12-05

One of the current directions in the development of modern pharmacy is the search for new sources of biologically active compounds and the expansion of the range of phytopharmaceuticals. In this context, the Snapdragon (Antirrhinum majus L.), a herbaceous plant from the Plantaginaceae family, stands out as a promising object of research due to its potential for yielding biologically active compounds with valuable pharmacological properties. The plant's chemical composition includes a significant number of bioactive compounds: amino acids, sugars, flavonoids, such as anthocyanidins, aurones, chalcones, and terpenoid compounds (iridoids, carotenoids). Due to the presence of these substances, the plant exhibits anti-inflammatory, wound-healing, antimicrobial, and antioxidant properties, which have been empirically confirmed. To expand the assortment of phytoremedies, we obtained a thick extract from the grass of this plant. The aim of this study was to examine the chemical composition of the Snapdragon herb extract, obtained from raw materials grown in Ukraine. Materials and methods: the object of study was the Snapdragon herb extract, obtained from a mixture of raw materials of the "Uvertura" and "Snappy" cultivars. Extraction was carried out using 70 % ethanol for 180 minutes by the maceration method. The plant material to solvent ratio was 1:10, and the raw material was ground into pieces measuring 5.0-8.0 mm. The chemical composition of the extract was analyzed using high-performance liquid chromatography (HPLC). The study was performed on a Milichrom A-02 liquid chromatograph with a ProntoSil-120-5-C18 AQ column, which was 75 mm long and 4 mm in diameter, with a stationary phase particle size of 5 µm. Two eluents were used in the experiment: A – 4 M lithium perchlorate solution, 0.1 M perchloric acid solution; and B – acetonitrile. The detectors were set to wavelengths of 210, 220, 230, 240, 250, 260, 280, and 300 nm. The thermostat temperature was set to 40 °C, and the flow rate of the mobile phase was 100 µL/min. The gradient of eluent B changed from 5 % to 100 % over 40 minutes. The initial sample volume was 800 µL, which was later increased to 4000 µL and 4300 µL. Chromatographic profiles were analyzed using the AlphaChrom software. Results: thirteen chemical compounds were identified using HPLC: flavonoids (luteolin-7-glucuronide, apigenin-7,4'-diglucuronide, quercetin-3-arabinofuranoside, quercetin-3-galactoside, quercetin-3-rhamnoside, kaempferol-3-glucoside, cyanidin), phenolcarbon chlorogenic acid, monosaccharide glucose, amino acids (phenylalanine, tryptophan), iridoid antirrhinoside and terpene myrcene. The obtained experimental data will be used for the standardization of the Snapdragon herb extract

Study of the elemental composition of Salvia splendens Sellow ex Roem. et Schultes

Yulia Berkalo — 2024-12-05

Introduction. The elemental composition of medicinal plants is related to physiological processes and environmental factors that occur during the development of the plant organism. Preparations based on raw materials from medicinal plants contain mineral complexes that play an active role in the human body's metabolic processes. The nutritional status of medicinal plants consumed by a person can negatively or positively affect his health. A deficiency of one or another element can cause various diseases, and therefore, it is essential to know and take into account the elemental composition of medicinal raw materials. Aims of the research. The study aims to conduct a comparative analysis of the qualitative composition and quantitative content of macro- and microelements in the soil and raw material of sage. Research methods. The content of macro- and microelements in the grass and roots of the brilliant sage and in the soil was determined by the method of atomic absorption spectrophotometry. Results and Discussion. The research results show that the grass and roots of the brilliant sage contain at least 18 chemical elements. Silicon, potassium, calcium, sodium and magnesium dominated the determined microelement composition of all samples, and aluminum, iron, manganese and zinc were among the microelements. Conclusions. For the first time, the qualitative composition and quantitative content of elements in the raw material of Salvia splendens and soil were determined by the method of atomic absorption spectrophotometry. The elemental composition of grass and roots was represented by 18 elements, six macroelements and 12 microelements. Throughout the study, certain regularities of the accumulation of elements in the raw material of brilliant sage were revealed. Silicon, silicon, potassium, calcium, sodium, and magnesium dominated the macroelements determined in all samples, and aluminum, iron, manganese, and zinc were among the microelements. The content of heavy metals was within normal limits for grass and, except for lead, for roots. The results will be used to develop parameters for standardising raw Salvia splendens.

Experimental determination of optimal parameters of virus-containing material inactivation by photodynamic method

Khrystyna Melentieva — 2024-12-05

Introduction. To obtain vaccine antigens, strains are usually inactivated either by heating, or by treatment with chemicals: formalin or propiolactone, acetone, alcohol, merthiolate, etc. These substances can enter into a chemical reaction with antigen proteins and change their chemical structure or configuration, forming covalent bonds between toxin proteins and a chemical factor, as a result of which abnormal antigenic determinants appear, increasing the reactogenicity and allergenicity of vaccine preparations. One of the current trends in the problems of improving vaccine preparations is the search for compounds and methods for inactivating pathogens that would be safe and would not lead to the appearance of abnormal antigenic determinants. To date, it has been established that pathogen inactivation systems (SIP) in blood products are effective against numerous bacteria, viruses, and parasites and are widely used in blood product decontamination technologies in transfusion medicine. Such as flavins, which is capable of photomodification, i.e., transfers a charge upon absorption of photons, which mediates cellular signaling or gene expression in endogenous protein complexes, such as light and oxygen sensing domains in bacteria and plants. Materials and methods. The object of research is the polyvalent Piophage® bacteriophage. Reference strains of bacteria (Staphylococcus aureus ATCC 25923 (F-49), Escherichia coli ATCC 25922 (F-50) and Pseudomonas aeruginosa ATCC 27853 (F-51). Bactericidal irradiators (bactericidal wavelength 253.7 nm) were used as an ultraviolet source. As photoinactivators/photosensitizers, a mixture (1:1:1) of solutions of riboflavin, riboflavin menadione sulfate (menadione) and pyridoxine hydrochloride in a concentration of 2×10-4% to 2×10-6% in polysorbate-80 was used ( Fluka, Austria) Determination of the infectious activity of phages was carried out by titration according to Appelman, according to Graz and using the spot test. Results and discussion. According to the results of determining the number of plaque-forming units (PFU/ml) of Piofag®, a significant decrease of this indicator was established when using РS. Extending the irradiation time to 45 minutes led to 100% virulicidal effect in the control as well. Testing for spontaneous reversion of these samples over a three-month period revealed no live virus. The obtained results indicate that ultraviolet irradiation (UV) causes, most likely, local changes in the viral nucleic acid in Piophage® viruses, leading to the replacement of individual bases, thus the reversion of bacteriophage strains that are part of Piophage® does not occur. Conclusion. According to the results of the experiments, the best results regarding the photoinactivation of the virus target material were obtained for 0.02% and 0.01% of the mixture of photosensitizers. UV radiation exposure time at these concentrations ranges from 5 to 15 minutes. For practical use, it is recommended to use 0.02% and 0.01% solutions of riboflavin, pyroxidin, and menadione in a ratio of 1:1:1 in the UFR mode for 5-15 minutes.

Keywords: phytoinactivators, bacteriophage, bacteria, vaccines.

Study of the antimicrobial activity and technological properties of a gel with catalpa bignonioides extract and dexpanthenol

Volodymyr Kovalev — 2024-12-05

Introduction. To create and improve existing medicines for the local treatment of purulent wounds, an active search for plant substances with a pronounced antimicrobial effect is underway. At the Department of Pharmacognosy of the National University of Pharmacy, Associate Professor Demeshko O. V. obtained a dry extract of Catalpa bignonioides leaves. The chemical composition of the extract is represented by a wide range of biologically active substances and, above all, phenolic compounds, which exhibit high antimicrobial, anti-inflammatory, analgesic, diuretic and reparative activity. The wound healing and bactericidal effect of the bark, fruits and leaves of Catalpa bignonioides is explained by the presence of phytoncides in the plant. The chemical composition and wide range of therapeutic activity of the extract of Catalpa bignonioides leaves makes it promising for use in the development of medicines with antimicrobial action. Thus, the development of gels with dry (hydrophilic fraction) extract of catalpa leaves and the study of antimicrobial and technological properties of the developed gel is relevant. The purpose of the study. Technological properties and antimicrobial activity investigation of a gel containing hydrophilic extract of Catalpa Bignonia and Dexpanthenol for the wounds on the proliferation phase treatment. Materials &methods. The quality control of the developed gel products for the treatment of wounds and burns was carried out in accordance with the methods and recommendations given in SPhU 2.0., Volume 1, section "Soft medicinal products for dermal application". The results of the research were statistically processed in accordance with the requirements of SPhU 2.3 of Article 5.3. Results & discussion. Noveon is one of the popular polymers used in the production of medicinal products in gel form. Catalpa leaf extract concentrations as well as gel base composition were selected based on literature review and previous studies. The composition of the studied gel sample: Catalpa leaf extract – 5%, Dexpanthenol – 3%, polysorbate 80 – 5%, Noveon® – 1%, methylparaben – 0.001%, TEA to pH 5.0, purified water to 100%. The medicine under study looks like a homogeneous, transparent gel, light brown in color with a specific smell of catalpa extract. The obtained results show that when stored for 10 days at room temperature, the organoleptic properties of the gel sample did not change. The antimicrobial activity of the gel samples was determined by the agar diffusion method. The results of the research showed that the gel sample with Catalpa leaf extract – 5% has a weak sensitivity to Escher strains. Coli, Ps. Aeruginosa, Pr. vulg., Ps. aeruginosa and C. albicans; moderate to St. Aureus and Bac. Subtilis. The obtained data on the antimicrobial activity of the gel sample allow us to state that the antimicrobial activity of the gel sample did not change when stored for 10 days at room temperature. The pH of a 10% aqueous solution of the gel was investigated potentiometrically according to the method given in SPhU 2.0. According to the results of research, it was established that the pH of the sample is 5.42 ± 0.23. The effectiveness of therapy using drugs with high osmotic activity can significantly slow down wound healing. For use in the second and third stages of wound healing, the use of soft dosage forms with medium and low osmotic activity is recommended. The investigated gel sample exhibits low osmotic activity and adsorbs up to 26% of water within 8 hours of the experiment and does not damage the granulation tissue. Conclusion. The researched gel shows antimicrobial activity against the strains that are more often sown on wounds. The pH value is 5.42 ± 0.23, which indicates the possibility of using the gel in the treatment of burns. The osmotic properties of the gel were studied. The gel sample shows low osmotic activity and adsorbs approximately 26% of liquid in 8 hours.

Key words: gel, extract of Catalpa bignonioides, technology, dexpanthenol.

Using in silico tools for primary screening and prediction of pharmacological activity of the range new theophyline derivatives

Liudmila Mosula — 2024-12-05

Introduction. Pharmacotherapy of various diseases requires the use of new highly effective drugs. At the initial stages of drug development, it is advisable to use in silico methods for the their screening. This saves time and money in selecting the most promising compounds for synthesis and in vitro and in vivo pharmacological studies. It is known that 7,8-disubstituted theophylline derivatives have a high potential for biological action. We chose 7-R-8-hydrazine derivatives of theophylline for the search of drug-like substances, since it is known that functional hydrazine derivatives are widely used in medical practice as drugs for the pharmacotherapy of depression, infectious diseases, hypertension, diabetes, ets. The aim of the work was primary screening and evalution of potential pharmacological activity of model molecules using virtual computer programs. Materials and methods. The research materials are derivatives of 4-(2-(1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)hydrazineylidene)heptanedioic acid with linear and branched alkyl substituents at the 7^th position of the basic heterocycle (12 compounds): methyl-, ethyl-, n-propyl-, n-butyl, i-butyl, n-amyl, i-amyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl. Research methods – freely available web tools SwissADME and SuperPred 3.0 for screening pharmacologically inactive molecules and selecting potential drug candidates.

Results and discussion. The virtual design of compounds (7,8-disubstituted theophyllines) was substantiated and implemented, and their screening was carried out using selected in silico methods. Using SwissADME, the physicochemical and pharmacokinetic parameters of the molecules were determined, drug-likeness, potential for oral administration and prospects for medicinal chemistry were established. SuperPred 3.0 webserver made it possible to establish the possible belonging of the studied compounds to certain ATC-classes in accordance with the WHO classification of drugs and target prediction of compounds. The biotargets with the highest probability of binding (˃ 90 %) and model prediction accuracy (˃ 80 %) were taken into account. The common predicted targets for them are Cathepsin D і Nuclear factor NF-kappa-B p105 subunit. The probability of the binding of the compounds 1–12 with the first target is in the range of 95,74–98,38 %, and with the second – 96,12–96,72 %. The accuracy of target prediction models ranges from 96,09–98,95 %. The obtained results were compared with the results of the prediction for theophylline and basic structure – 4-(2-(1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)hydrazineylidene)heptanedioic acid. The results of in silico studies indicate the drug-like nature of molecules for which a fairly easy synthesis is predicted. Conclusions. A virtual screening of the studied compounds was carried out and some relationships «structure – biological activity» were established. Further chemical modification of the the structures should not involve the elongation of the alkyl substituent at position 7 of the basic heterocycle, because this does not significantly change their pharmacological potential, but negatively affects the ADME profile and limits oral biovailability. The results of in silico prediction confirmed the prospects of further research for biologically active compounds among 7,8-disubstituted theophyllines.

Keywords: 7-R-8-hydrazine theophyllines, in silico prediction, SuperPred 3.0, SwissADME, ADME properties, Cathepsin D, Nuclear factor NF-kappa-B p105 subunit, peripheral vasodilatory, obstructive airway diseases.

Webometric analysis of the availability of semaglutide-based anti-obesity drugs

Yuliia Kremin — 2024-12-05

Introduction. According to the WHO, in 2022 every eighth person in the world suffers from obesity. Future forecasts are that by 2025, 167 million adults and children will experience poor health as a result of being overweight or obese. Accordingly, this issue gives rise to the need for people to find weight loss methods, and in recent years, drugs based on semaglutide have become in great demand as an easy way to lose weight, despite the presence of a large number of possible side effects. The purpose of this work was a webometric analysis of the availability of such drugs on the market of Ukraine. Materials and methods. The research materials were data from online search pages for medicines in pharmacies of Ukraine, as well as 12 websites that illegally offer to purchase the above-mentioned drugs were investigated. Webometrics, modeling and scientific generalization were used among the methods. Research results. After analyzing the pharmaceutical market of Ukraine, we found out that there is only one semaglutide-based drug registered in Ukraine – Ozempik. Currently, there is a shortage of this medicine, as there were only 27 offers for the availability of this drug in Ukrainian pharmacies as of 07/23/2024. Nevertheless, illegal Internet platforms (we have identified 10 online services that position themselves as platforms for the sale of drugs by delivery / imports them from European pharmacies, and 2 online services with biologically active supplements and sports nutrition) offer easy availability of Ozempik (injectable dosage form). In addition, there are two other medicines available for purchase on online resources - Vegovi (injectable dosage form) and Ribelsus (tablet dosage form), which are not registered in our country. Conclusion. The availability of semaglutide-based drugs in Ukraine was studied using a webometric search. Its shortage in licensed distribution points (pharmacies) was established, while the unimpeded presence of unlicensed sales was revealed, which requires strengthening of state control over the illegal trade in these medicines.

The impact of long COVID on the quality of life of patients living in the frontline city during hostilities

Olena Grishyna — 2024-12-05

The aim of this study was to assess the quality of life (QoL) of patients with long COVID living in the frontline city Kharkiv during hostilities between Russia and Ukraine. Materials and Methods: Three groups of patients were formed using the «case-control» design. Group 1 - patients with long COVID living in Kharkiv (n = 18). Group 2 - patients who recovered from COVID and live in Kharkiv (n = 36). Group 3 - internally displaced persons (IDPs), n = 36. Pairs were matched based on criteria such as age, gender, comorbid conditions, and concomitant medication. The WHOQOL-bref questionnaire in Ukrainian was used to assess QoL. Results: QoL in Group 1 was 2,5 ± 0,73 compared to 3,1 ± 0.94 in Group 2 (p = 0,021) and 2,2 ± 0,69 in Group 3 (p _1-3 = 0,145, p _2-3 < 0,0001). The health status (HS) was the worst in Group 1 – 2,2 ± 0,71 vs 3,4 ± 0,99 in Group 2 (p _1-2 < 0,0001) and 2,8 ± 0,83 in Group 3 (p _1-3 = 0,011, p _2-3 = 0,068). Physical health was also worst in Group 1 – 34,42 ± 1,.60 vs 56,48 ± 18,31 in Group 2 (p < 0.000...) and in Group 3 – 46,28 ± 16,73 (p _1-3 = 0,01, p _2-3 = 0,02). Psychological domain did not differ significantly between Groups 1 and 2 – 51,29 ± 17,38 vs 69,27 ± 22,86 (p = 0.65), but was lower in Group 3 – 39,72 ± 13,71 (p _1-3 = 0,01, p _2-3 < 0,0001). Social relationships were rated lower by patients in Group 3 – 49,51 ± 15,44 compared to patients in Group 1 – 59,12 ± 17,89 (p = 0,046) and Group 2 – 63,19 ± 21,35 (p = 0,0027). Environment domain was lowest in Group 3 – 52,09 ± 16.32, although it did not differ significantly fro Group 1 – 57,63 ± 18,21 (p = 0,65), unlike Group 2 – 69,27 ± 22,86 (p = 0,0005). Conclusions: Patients with long COVID had a lower QoL compared to recovered patients, which was comparable to that of IDPs. Health status in these patients was the worst compared to both recovered patients and IDPs. Physical health was worst in the group of patients with long COVID, while psychological domain was poorest in the IDPs group, which also had the lowest social relationship domain. Environmental domain was equally low in both groups of patients with long COVID and IDPs.

Keywords: long COVID, quality of life, internally displaced persons, hostilities.

Pharmaceutical ethics: situational analysis of the state and problems

Kateryna Dorykevych — 2024-12-05

Introduction. Pharmaceutical ethics is the science of moral norms of pharmacists’ behavior in the process of their professional activity. The work of pharmacists in modern conditions is accompanied by new challenges (the development of technology and artificial intelligence), and even danger, given the recent Covid-19 pandemic and the current military actions of Russia on the territory of our country. The purpose of our research was to study the current state and problems in pharmaceutical ethics. Materials and methods. Research materials were scientific publications on pharmaceutical ethics and ethical problems in pharmacy, Codes of Pharmaceutical Ethics of Ukraine, Poland, USA, Canada, and Spain. The methods of the system approach, analysis, synthesis, comparison, generalization and the questionnaire survey method were used. Research results. It has been established that the most common ethical problems in the modern pharmaceutical field are conflicts between the patient's right to autonomy and his health interests, as well as between the patient's right to information and the obligation to follow the doctor's recommendations; the presence of queues in pharmacies, problems with the dispensing of medicines with incorrectly written prescriptions. A comparative analysis of the Ethical Codes of Pharmacists of Ukraine, the USA, Poland, Spain, and Canada showed that, in general, their content is very similar, in particular, in matters of providing patient-centered pharmaceutical care. A questionnaire for surveying pharmacists on the topic of pharmaceutical ethics was developed, it was tested and preliminary results were obtained, indicating a high degree of theoretical knowledge of pharmaceutical ethics norms among pharmacists. Conclusion. Pharmaceutical ethics is one of the basic components of the activities of pharmacists, and the modern world poses new challenges in the form of artificial intelligence, pandemics, and wars, which affect pharmaceutical practice. Professional ethics of pharmacists includes their responsibility to ensure the patients` interests, including their rights to autonomy, privacy, confidentiality and information rights.