Aim. A comprehensive study on the antimicrobial properties of new 1,2,4-triazole derivatives using the tools of in silico and in vitro studies. Materials and methods. Computer search techniques were used to find a compound with a strong antibacterial activity; in silico molecular docking (receptors for class A (PDB id: 1n9b) and class A SHV-1 (PDB id: 2zd8) beta-lactamase) and in vitro studies on 16 types of microorganisms. Then, the in silico analyzed compounds were tested in vitro for antimicrobial activity. After preparing solutions of different concentrations, the culture growth was measured on a zonal scale for detecting sizes of microbial growth inhibition zones after 24 hours (Antibiotic Zone Scale-C, model RW297, India) and a TpsDig2 software (2016, F. James Rohlf). Statistical analysis of the study results was carried out using the Statistica 13 software (StatSoft Inc., USA). Results. From the results of molecular docking, a strong binding affinity to class A enzymes has been found in compounds 2, 7, so they could be effective in the treatment of infection caused by K. pneumoniae. The ascending order of the predicted binding affinity through the calculated score for TEM and SHV enzymes was as follows: compound 4 < compound 3 < compound 1 < compound 7 < compound 2. According to our results, the studied chemical compounds 1–4, 7 inhibited the growth of many microbial species of the Enterobacteriaceae, Morganellaceae, Pseudomonadaceae, Enterococcaceae, Staphylococcaceae and Bacillaceae families. Conclusions. For the first time, studies on the complex inhibitory effect of chemical compounds 1–4, 7 were conducted using 16 bacterial strains. Evident antibacterial effects of the studied compounds have been established: compound 1 against 13, compound 2 – 9, compound 3 – 10, compound 4 – 7, compound 7 – 10 out of 16 tested polyresistant bacterial strains.

Foot fungus (Candida, molds, dermatophytes) is a fairly common problem. According to the WHO, one-fifth of the world’s population is affected by fungal skin diseases. The prevalence of mycosis of the feet, which affects every second person, is especially increasing. Such a pathology can appear quite unexpectedly and at an inappropriate time. Today, Ukraine is under aggressive pressure from its northern neighbor, and military personnel are not only constantly at risk of receiving combat injuries and wounds, but also due to active hostilities, they may not have access to the necessary hygiene products, get cold, overheat in the sun, or not have time to change their clothes in time. and shoes. The reality is the absence or delay of treatment; the disease progresses and can spread quickly. If mycosis has appeared in one soldier, it can quickly affect others. Therefore, the problem of providing medical and pharmaceutical care is an urgent issue today. Expanding the assortment of drugs with the above action will ensure the needs of the Armed Forces and civilian patients with this dermatological pathology. It will be able to optimize antifungal therapy regimens. For quite a long time, 1,2,4-triazole derivatives have been a promising class of organic compounds that attract the attention of scientists from various fields. It has been proven that 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol has high antifungal activity. A potential medicinal product based on this medicinal substance can be used for the treatment of various dermatological diseases. To continue the creation of new effective dosage forms for the effective therapy of mycosis of the feet, the urgent task of today is the development of an express, accurate, reliable, and affordable method of quantitative determination of the substance under study. The aim of the work is to develop an express, sensitive and easy-to-implement UV-method for the quantitative determination of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol. Materials and methods. The research object is a working standard sample of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol provided by NUNVF, LLC “Brovapharma” according to the “Research and production technological regulations for the production of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazol-4-yl)imino)methyl)phenol” developed based on scientific developed by the Ukrainian Military Medical Academy in conjunction with the National Military Medical Clinical Center “Main Military Clinical Hospital” (term of validity of the regulations until 12/31/2034). Isopropanol of grade “chemically pure” was used as a solvent. Analytical equipment: spectrophotometer Specord 200, electronic scales Radwag XA 210.4Y, class A measuring vessels. Results. An express, eco-friendly spectrophotometric method was developed for the quantification of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol in isopropanol area, having analytically maximum at 310 nm. The studied solutions are stable for 30 minutes. The analytical technique is linear in the range of concentrations 0.440–0.754 mg/100 ml (70–130 %). The detection and quantification limits were 5.80 % and 15.70 % respectively. The score was 0.76, according to the “greenness” icon of the analytical technique, using the tools AGREE. The prediction of the total uncertainty of the results of the developed method is 1.70 % (max∆As 2.00 %). The proposed method is relevant according to the requirements of the State Pharmacopoeia of Ukraine. Conclusions. Pharmaceutical development, introduction into industrial production and further prescribing by dermatovenerologists of an effective, safe, and harmless medicinal product will help to expand the range and reduce the level of high import dependence of the domestic market of medicinal products, which will create a more complete and balanced system of medicinal supply in Ukraine and optimize antifungal therapy schemes.

1,2,4-Triazole derivatives open up wide horizons for modern medicinal chemists to develop innovative drugs. The use of 1,2,4-triazole derivatives in pharmacological research is based on their ability to produce an effective effect on biological systems and interact with molecular targets. These azoles can be used to regulate various physiological processes, which opens up the possibility of their effective use in the treatment of various diseases. Targeted modification of the structure of 1,2,4-triazole derivatives opens up wide opportunities for the creation of biologically active compounds with improved properties, which contributes to further advances in pharmaceutical research and the development of new, effective drugs. The aim of this work is to predictively assess the pharmacological potential of 1-alkyl-4-(((5-nitrofuran-2-yl)methylene)amino)-1,2,4-triazole halides by in silico studies. Materials and methods. ADME-analysis is a method of studying the physical-chemical and pharmacokinetic parameters of the studied substances using the online resource SwissADME. Molecular docking is a method of predicting and evaluating the interaction between a ligand molecule and the three-dimensional structure of the target protein. The ligands have been prepared with the software MarvinSketch 6.3.0, Hyper Chem 8, and AutoDockTools-1.5.6, whereas the software packages Discovery Studio 4.0 and AutoDockTools-1.5.6 have been used for the preparation of enzymes. The Vina program was used for direct molecular docking. Results. A prescreening analysis was conducted on a virtual series of 1-alkyl-4-(((5-nitrofuran-2-yl)methylene)amino)-1,2,4-triazole halides, recognized as potential sources of biologically active substances. The study involved determining the main physicochemical characteristics and unveiling general pharmacokinetic parameters of the molecules. The Vina program was employed to identify the nature and number of amino acid residues in the active sites of model enzymes interacting with the proposed ligands. Results indicate the highest affinity for lanosterol 14α-demethylase. However, the analysis of ligand complexes with cyclooxygenase-2 and anaplastic lymphoma kinase suggests a low probability of a significant effect on these enzymes. Conclusions. The overall prognosis for bioavailability in the case of oral administration of dosage forms with the investigated substances is favorable. Pharmacodynamics in silico studies allow us to identify 1-heptyl- and 1-octyl-4-(((5-nitrofuran-2-yl)methylene)amino)-1,2,4-triazolium bromides as potential antifungal agents that can reasonably be involved in further in-depth studies of this type of activity.

The heterocyclic system of 1,2,4-triazole enables the successful creation of promising biologically active compounds. By creating a range of derivatives based on 4-amino-3,5-dimethyl-1,2,4-triazole, the spectrum of potential biologically active compounds can be expanded. The aim of the work was the synthesis and in silico justification of the prospects for the search for biologically active compounds among 4-amino-3,5-dimethyl-1,2,4-triazole derivatives. Materials and methods. The work uses modern methods for synthesizing organic compounds, followed by confirmation of their individuality and structure through the analysis of physical-chemical parameters and spectroscopic techniques such as 1H NMR, IR spectroscopy, elemental analysis, and chromatography-mass spectrometry. To assess the similarity of the synthesized compounds to medicinal products, the SwissADME online tool was employed. The probability of impact on a number of enzyme systems (cyclooxygenase-2, lanosterol 14α-demethylase, anaplastic lymphoma kinase) was estimated using molecular docking. Results. A series of newly synthesized derivatives of 4-amino-3,5-dimethyl-1,2,4-triazole was obtained, and the synthesis conditions were optimized and their structures were confirmed. It was determined that there is a high probability of influencing lanosterol 14α-demethylase, highlighting the significance of further research on the antifungal activity of the synthesized compounds. Additionally, the potential influence on the activity of cyclooxygenase-2 and anaplastic lymphoma kinase was discovered. However, the probability of exhibiting the corresponding activities, namely anti-inflammatory and anti-cancer, is low. Physical indicators, parameters of pharmacokinetics, and drug-likeness are important, which determines the prospects of creating biologically active substances based on the synthesized series of compounds. Conclusions. A series of 4-((R-iden)amino)-3,5-dimethyl-1,2,4-triazoles were synthesized, and their general physical-chemical properties were determined. The overall potential for creating innovative biological products based on these compounds was assessed using in silico methods for predicting the activity of substances.

Compared to the previous year, the share of healthcare expenditure in the state budget of Ukraine has decreased, which is associated with increased funding for the security and defense sector. In terms of gross domestic product, healthcare spending has reduced to 2.8 %, which corresponds to the figures for 2019. These circumstances indicate the importance of proper budget utilization, including effectively regulating medicine prices. One of the key elements of rational healthcare budget usage is the development and implementation of external reference pricing (ERP). A well-formulated and implemented ERP policy for pharmaceuticals contributes to improving patient access to essential medicines (EMs). The aim of this study is to analyze the current status of ERP implementation in Ukraine and provide recommendations for improving this policy. Materials and methods. During the research process, an analysis of the ERP’s current regulatory framework was conducted, and ERP implementation in Ukraine was assessed according to adherence to the 14 best practice principles of ERP proposed by Sullivan, Kanavos & Kalo in 2015. Results. In Ukraine, ERP has been introduced for medicines from the National Essential Medicine Lists (NEML) and the “Affordable Medicines” program. The Ministry of Health (MoH) of Ukraine has approved a Register of marginal wholesale prices for medicines purchased with state budget funds and subject to price regulation. Currently, the register includes 1239 medicinal products, of which 1233 are from NEML and 6 have undergone Health Technology Assessment (HTA). Approximately 58 % of medicines have a set price through ERP, 24 % are regulated by internal reference pricing (IRP), and nearly 18 % have declared prices. This indicates a lack of uniformity in approaches to price regulation for medicines and requires further improvements. According to the latest update of the Register of medicines for reimbursement under the state medical guarantees program, there are 486 medicines, including 72 insulins and 21 immunosuppressive medicines (184 medicines are provided with co-payment). Different approaches, including different reference countries and price calculation algorithms, are applied for the price regulation of medicines in NEML and the “Affordable Medicines” program. An assessment of the implementation of the ERP system in Ukraine based on the 14 best practice principles of ERP proposed by Sullivan, Kanavos & Kalo in 2015 showed that the current policy does not adhere to all principles. Conclusions. The analysis revealed different approaches to pricing for medicines NEML and the “Affordable Medicines” program, indicating the need for harmonizing pricing policies for different lists. The adoption of a unified positive list can contribute to improving pricing policies and efficient resource utilization. Collecting, disseminating, and exchanging data on drug prices is crucial to support transparency in pricing and its control. Regular monitoring of prices in the market will help ensure compliance with pricing policies and take appropriate measures in case of violations. The implementation of a unified pricing regulation policy for medicines in Ukraine is an important step towards European integration and compliance with international standards.

Each patient presents a unique set of characteristics and challenges when it comes to acute cerebral ischemia resulting from craniocerebral injury. The aim of this study is to investigate the utilization of Thiocetam as part of a comprehensive treatment approach for combat-related cerebral contusion and to assess the therapeutic effects of Thiocetam in patients with mild and moderate closed combat craniocerebral trauma in comparison to standard basic therapy. Materials and methods. 79 patients with mild and moderate closed combat craniocerebral trauma were examined. Among them, 76 patients experienced craniocerebral trauma due to an explosive blast injury, which included conditions such as brain concussion, mild cerebral contusion, and cranial vault fractures. All patients were admitted to the department during the acute period of their injuries. During the study, various clinical and functional methods were employed to assess the condition of the central nervous system. These methods were used to evaluate the effects of the complex treatment administered to the patients. Results. The administration of Thiocetam to the patients did not result in an increase in excitability, nervousness, or sleep disturbances. Furthermore, the examination of autonomic reactivity following Thiocetam treatment revealed that the indicator of normal autonomic reactivity increased to 60 % in the treated group, whereas it only increased to 42 % in the control group. Additionally, the patients with initially heightened vegetative reactions experienced a decrease from 42.8 % to 17.9 % in the treated group, while the control group saw a decrease from 38.5 % to 23.1 %. In terms of clinical outcomes, a positive effect was observed in 94 % of patients in the Thiocetam-treated group within the first 5 days. In comparison, the control group showed a positive clinical effect in 76 % of cases. This improvement was evident both in the clinical field and based on indicators of autonomic reactivity in EEG data, as well as cognitive function assessed by the MMSE cognitive function test scale. Conclusions. The utilization of Thiocetam during the acute phase of mild and moderate closed combat craniocerebral trauma enhances the neuroprotective effects of basic therapy. The combined drug Thiocetam, which possesses both nootropic and neuroprotective effects, offers the advantage of reducing or even avoiding the side effects commonly associated with traditional racetam nootropics.

One of the most common eye diseases is a burn injury. Hence, one of the pressing challenges in the field of pharmacy today is the development of new ophthalmic medications, specifically eye drops. Researchers from the Department of Pharmaceutical, Organic, and Bioorganic Chemistry at Zaporizhzhia State Medical and Pharmaceutical University, led by Professor I. A. Mazur, have successfully synthesized a novel compound. This compound is a derivative of 1,2,4-triazole, specifically (S)-2,6-diaminohexanoic acid 3-methyl-1,2,4-triazolyl-5-thioacetate. Notably, this compound demonstrates anti-inflammatory, wound-healing, and reparative activities. The aim of the work is to develop a method of quantitative determination of the active substance in Angiolin eye drops by the method of high-performance liquid chromatography. Materials and methods. The research employed a liquid chromatograph equipped with a UV detector. A column Hypersil ODS C-18 measuring 250 by 4.6 millimeters with a particle size of 5 microns was used. Results. It was determined that the angiolin content in the 1 % eye drops in series 1 falls within the range of 0.985 to 1.010 grams. This indicates that, in terms of the active substance content, the studied series complies with the requirements of the State Pharmacopoeia of Ukraine. Conclusions. As a result of the conducted research, a method for quantitatively determining the active substance in Angiolin eye drops using high-performance liquid chromatography was developed.

About half of the drugs currently produced are chiral compounds, and about 90 % of these compounds are sold as racemates, consisting of an equimolar mixture of two enantiomers. Although they have the same chemical structure, most of the optical isomers of chiral substances show marked differences in biological activity. It is known that the presence of a single asymmetric atom has become almost an integral part of advanced drug design. The aim of this work was to determine the angle of rotation of the polarization plane of solutions of some S-derivatives of 4-R-5-((((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl))-4H-1,2,4-triazole-3-thiols and the establishment of regularities between the structure of the studied molecules and their optical activity. Materials and methods. The subject of the study was 2-[5-R1-4R2-1,2,4-triazole-3-ylthio]-1-aryletanols. The study of the angle of rotation of the plane of polarization of solutions of newly synthesized compounds was carried out using an Atago AP-300 polarimeter and the DFU 2.2.7 physical-chemical analysis method “Optical rotation”. Results. The results of the physical-chemical analysis were carried out that the studied compounds exhibit optical activity. The compound 1-((4-methyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)-2-phenylethan-1-ol (+43° [deg∙g/cm3∙dm]). The only levorotatory substance was 1-(4-fluorophenyl)-2-((4-methyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio))methyl)-4H-1,2,4-triazole-3-yl)thio)ethan-1-ol with specific rotation [α]D20 = -43° [deg∙g/cm3∙dm]. Conclusions. Studies had shown that 1-(4-fluorophenyl)-2-((4-methyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl))thio)methyl)-4H-1,2,4-triazole-3-yl)thio)ethan-1-ol was able to rotate the light polarization plane to the left, which was evidence of the advantage of the S-enantiomer in the racemic mixture, and therefore this compound was considerable interest for further preclinical research. Also, all other analyzed compounds behave as optical isomers.

Цель исследования – на основании результатов электрокардиографии (ЭКГ) и их анализа оценить кардиопротекторную активность и особенности действия потенциального препарата «Гипертрил» при экспериментальной хронической сердечной недостаточности (ХСН).Экспериментальная часть работы выполнена на 70 белых беспородных крысах массой 190 – 220 г. ХСН моделировали введением доксорубицина (внутрибрюшинно в кумулятивной дозе 15 мг/кг, разделенной на 6 инъекций в течение 14 дней). Исследуемые препараты – Гипертрил вводили 1 раз в сутки внутрижелудочно в дозе 3,5 мг/кг на протяжении 30 суток; метопролола сукцинат – по такой же схеме в дозе 15 мг/кг. Наличие ХСН подтверждали методом ЭКГ при помощи компьютерного анализатора Cardio Com-2000 plus (ХАИ-медика, Украина).Моделирование ХСН у экспериментальных животных приводило к элевации сегмента ST над изолинией примерно на 0,1 мВ (в 14,3 раза), к увеличению сократительной функции желудочков (увеличение амплитуды зубца R на 36 %) в сочетании с удлинением фазы их деполяризации (комплекс QRS) на 11,5 % и реполяризации (зубец Т) на 9,5 % относительно длительности сердечного цикла, снижением спектральной мощности сердечного ритма TPW и увеличением стресс-индекса SI в 2,7 раза, к сокращению времени электрической диастолы до (4,2 ± 0,2) мс (в 11,6 раза). На фоне введения метопролола длительность реполяризации более чем на 40 % превышала аналогичный показатель у интактных крыс и нелеченных животных с ХСН, и составляла 50 % от длительности сердечного цикла RR. Длительность электрической диастолы ТР хотя и увеличивалась в 2 раза по сравнению с животными с ХСН, но оставалась при этом в 5 раз короче, чем у интактных животных. На фоне введения Гипертрила на ЭКГ отмечалась нормализация амплитуды желудочкового зубца R и нормализация амплитуды зубца реполяризации T, существенное снижение амплитуды сегмента ST над изолинией – в 4 раза по сравнению с контрольной группой и в 2,5 раза по сравнению с животными, получавшими курсом метопролол, нормализация длительности комплекса QRS и зубца Т, а также интервала ТР. Это свидетельствует о том, что курсовое применение Гипертрила предотвращает формирование диастолической дисфункции.Полученные результаты являются экспериментальным обоснованиям перспективности дальнейшего исследования потенциального препарата «Гипертрил» в виде таблеток.

Today, the important problem is the creation of new decamethoxine and thiotriazoline based drugs for the treatment of stomatitis. The aim of the work is to develop a method for quantitative determination of decamethoxine and thiotriazoline in the model mixture (1:25) by spectrophotometry. Materials and methods. Series 6 model mixtures were made at the ratio of decamethoxine and thiotriazoline 1:25. We used certified substances: thiotriazoline series GTT 3460911 (manufacturer: State Enterprise Chemical Reagents Plant, Kharkiv), decamethoxine series № 010915 (manufacturer: LLC “PHARMCHIM”). Optizen POP spectrophotometer, polyvinyl alcohol, hydrochloric acid, and eosin were used. Results. A method for quantitative determination of decamethoxine and thiotriazoline in MS was developed. It was established that the content of active substances in MS is thiotriazoline from 0.5021 to 0.5096, decamethoxine from 0.0207 to 0.0211. Conclusions. A method for quantitative determination of decamethoxine and thiotriazoline in MS has been developed. The method of quantitative determination of decamethoxine and thiotriazoline in MS is reproducible.

Throughout human history, cataracts have been one of the leading causes of blindness. For this disease, we studied the market of drugs of domestic and foreign production. The object of our study was the subgroup S10X Other ophthalmic drugs. Employees of the Department of Pharmaceutical Chemistry of Zaporizhzhia State Medical University (ZSMU) together with specialists of the NGO “Pharmatron” was synthesized a new compound, which was named Angiolin. A rational dosage form in the form of eye drops was proposed for the new drug. Since the drops continue to be the most common and widely used in practice dosage form. We have previously selected the optimal content of the active substance in eye drops. As is known from the technological parameters, eye drops must be isotonic, ie in their composition should be added excipients. The aim of our work is to select the concentration of excipients for the manufacture of eye drops Angiolin. Materials and methods. During the work at the Department of Pharmaceutical Chemistry of ZSMU, three solutions of eye drops Angiolin with different composition were prepared, and later the theoretical osmolarity was calculated. Results. Accurate theoretical calculation of the osmolarity of solutions containing substances with high molecular weight, complex total extracts, and highly concentrated solutions is impossible. Since the excipient was used methylcellulose, it was better to perform such a calculation experimentally, through the determination of osmolality. On the basis of the conducted researches, for correction of osmolarity, we were chosen – sodium chloride. Sodium chloride was selected at a concentration of 7.0 g/l, which creates an osmolality of the drug equal to 234.3 mosmol/kg. The estimated value at the same concentration of sodium chloride was 239.56 mosmol/l. The value of osmolarity of eye drops was calculated from it makes 302,18 mosmol/l that was confirmed the correctness of the chosen concentration of sodium chloride as a part of eye drops. Conclusions. Based on the above, we selected the concentration of excipients for the manufacture of eye drops Angiolin.

Мета роботи. Розробка складу та технології таблеток гамма-аміномасляної кислоти з тіотриазоліном. Матеріали і методи. В роботі використовували гамма-аміномасляну кислоту (Sigma-Aldrich, США); тіотриазолін (Державне підприємство «Завод хімічних реактивів» Науково-технологічного комплексу «Інститут монокристалів» НАН України), допоміжні речовини вітчизняного і закордонного виробництва. Таблетки ГАМК з тіотриазоліном готували методом вологої грануляції. Пресували таблетки за допомогою лабораторного таблеткового пресу 6000S (Білорусь) з діаметром пуансонів 10 мм та контролювали їх фармако-технологічні властивості. Результати й обговорення. Для вивчення трьох факторів використовували латинський квадрат третього порядку. Вивчали вплив природи допоміжних речовин на зовнішній вигляд таблеток, однорідність маси, стираність, розпадання та стійкість до роздавлювання. За результатами експериментальних досліджень проводили дисперсійний аналіз експериментальних даних та робили висновки про вплив вивчених факторів на показники якості таблеток ГАМК з тіотриазоліном. Висновки. За результатами проведених досліджень вивчили вплив трьох факторів допоміжних речовин на зовнішній вигляд, однорідність маси, стираність, стійкість до роздавлювання та розпадання таблеток. Дисперсійний аналіз результатів дозволив вибрати кращі ДР (МКЦ 301, 3 % розчин МЦ 100, магнію стеарат), які забезпечують фармакопейні фармако-технологічні вимоги, що висуваються до таблетованих лікарських форм.

Today in Ukraine, stroke remains the second and most common cause of premature mortality and disability. More than 111.000 new cases of stroke occur every year in Ukraine. This is a very topical medical and social problem worldwide. Today, a promising area of primary neuroprotection in cerebral ischemia is to correct the imbalance of excitatory and inhibitory neurotransmitter systems through the activation of natural inhibitory processes. Our attention was drawn to the natural inhibitory neurotransmitter glycine and its role in the mechanisms of acute cerebral ischemia. There is evidence of the ability of the thiotriazoline antioxidant to potentiate the therapeutic effect of neurometabolic cerebroprotectors. Based on this, we have created a new combination drug based on glycine with thiotriazoline. For the new combination drug, a rational dosage form of the tablet was selected. The purpose of this work is to select excipients for producing glycine tablets with thiotriazoline by direct compression, to study their effect on bulk density, bulk density after shrinkage, fluidity, and angle of natural inclination. Materials and methods. The studies were used: glycine (manufacturer: China); Thiotriazoline (manufacturer: State Enterprise Chemical Reagents Plant of the Institute of monocrystals of the NAS of Ukraine), certified excipients based on microcrystalline cellulose, granulated sugars, granulated inorganic salts, lubricating as well as domestic. At first, morphometric studies of glycine powders, thiotriazoline, and mixtures of glycine with thiotriazoline were conducted. In the course of the work, four groups of excipients, factors, and their levels were studied. To study the four qualitative factors, we used the Greek-Latin square 4 × 4. The bulk density, the bulk density after shrinkage, the fluidity, and the angle of the natural slope of the glycine powder masses with thiotriazoline were studied. Results. According to the results of the experimental studies, the variance analysis of the experimental data was carried out and conclusions were drawn about the influence of the studied factors on the quality parameters of the glycine powder masses with thiotriazoline Conclusions. In the course of the researches, the influence of four groups of excipients on the bulk density, the bulk density after shrinkage, the fluidity, the angle of the natural slope of the glycine powder masses with thiotriazoline were studied. According to the results of the analysis of variance, optimum auxiliaries were selected which provide quality according to the studied parameters.

Today, diseases caused by pathogenic bacteria are the most dangerous, as they can not only affect the quality of human life, but also lead to death.According to the WHO, pathogenic bacteria namely, mycoses affect from 1/5 to 1/3 of the world's population, more than a third (37.8 %) of them cause yeast-like (Candida). Over the past 20 years, there has been a 15-fold increase in the frequency of infectious inflammatory diseases of candidiasis etiology.After examining the range of drugs on the pharmaceutical market of Ukraine and abroad, it was found that the following drugs of foreign origin are currently used for the treatment of these diseases: Methyluracil (Lekhim, Ukraine), Solkoseril (Birsfelden, Switzerland), Mexidol (PHARMASOFT, Moscow, RF).Based on the above it is seen that the range of drugs for the treatment of oral mucosa diseases is limited. All of the above shows the need for the creation of a new domestic drug exhibiting antimicrobial, fungicidal, reparative activity.The aim of our work is to create a new drug based on the model mixture of Thiotriazoline and Decamethoxinum, which exhibit antimicrobial, fungicidal, repertoire activity.Materials and methods. Thiotriazoline, decamethoxinum, model mixture. The studies were carried out by agar diffusion (well method) to study antimicrobial activity. Model mixtures with decamethoxinum were made from 0.5 to 5 mg; thiotriazoline – 200 mg. Antimicrobial activity of these model mixtures was carried out.Results. The model mixture of thiotriazoline and decamethoxinum in antimicrobial and fungicidal action was significantly superior to decamethoxinum by 54 % in the degree of growth inhibition of S. aureus, by 120 % in the degree of growth inhibition of E. coli, by 57 % in the degree of growth inhibition of P. aeruginosa, and by 108 % in the degree of growth retardation of C. albicans at 106 CFU/ml of medium.Conclusion. The model mixture of thiotriazoline and decamethoxinum exhibits high antimicrobial and fungicidal activity.

Мета роботи: вибір допоміжних речовин (ДР) для отримання сублінгвальних таблеток гліцину з тіотриазоліном методом прямого пресування, вивчення їхнього впливу на процес пресування, зовнішній вигляд, однорідність маси, стираність, стійкість до роздавлювання, розпадання та органолептичний показник таблеток. Матеріали і методи. У дослідженнях використовували: гліцин (Shiiiazhuana lirona Pharmaceutical Co., Ltd. Китай), тіотриазолін (Державне підприємство "Завод хімічних реактивів" Науково-технологічного комплексу "Інститут монокристалів" НАН України), сертифіковані ДР вітчизняного і закордонного виробництва. Таблетки гліцину з тіотриазоліном готували методом прямого пресування. Пресували таблетки за допомогою лабораторного настільного таблеткового пресу 6000S (Білорусь) з діаметром пуансонів 10 мм. Результати і обговорення. Для вивчення чотирьох якісних факторів використовували греко-латинський квадрат 4х4. Вивчали зовнішній вигляд, однорідність маси, стійкість таблеток гліцину з тіотриазоліном до роздавлювання, стираність (PHARMA TEST AG Siemensstrasse 5 D-63512 Hainburg), розпадання таблеток (ERWEKA ZTx20), органолептичний показник (солодкість-гіркість). За результатами досліджень проводили дисперсійний аналіз отриманих даних та робили висновки про вплив вивчених факторів на показники якості таблеток гліцину з тіотриазоліном. Висновки. В результаті проведених досліджень було вивчено вплив чотирьох груп ДР на процес пресування, зовнішній вигляд, стираність, стійкість до роздавлювання, розпадання, органолептичний показник (солодкість-гіркість) характеристики сублінгвальних таблеток гліцину з тіотриазоліном, які були отриманні методом прямого пресування. Дисперсійний аналіз результатів дозволив вибрати кращі ДР, які забезпечують всі фармако-технологічні вимоги, які висуваються ДФУ до таблеток як лікарської форми.

THE INFLUENCE OF SUBLINGUAL TABLETS OF THIOTRIAZOLIN AND DECAMETHOXIN ON ALLERGY MARKERS AND TOXICITY INDICATORS

Today, diseases caused by pathogenic bacteria are the most dangerous, as they can not only affect the quality of human life, but also lead to death. According to the WHO, pathogenic bacteria namely, mycoses affect from 1/5 to 1/3 of the world's population, more than a third (37.8 %) of them cause yeast-like (Candida). Over the past 20 years, there has been a 15-fold increase in the frequency of infectious inflammatory diseases of candidiasis etiology. After examining the range of drugs on the pharmaceutical market of Ukraine and abroad, it was found that the following drugs of foreign origin are currently used for the treatment of these diseases: Methyluracil (Lekhim, Ukraine), Solkoseril (Birsfelden, Switzerland), Mexidol (PHARMASOFT, Moscow, RF). Based on the above it is seen that the range of drugs for the treatment of oral mucosa diseases is limited. All of the above shows the need for the creation of a new domestic drug exhibiting antimicrobial, fungicidal, reparative activity. The aim of our work is to create a new drug based on the model mixture of Thiotriazoline and Decamethoxinum, which exhibit antimicrobial, fungicidal, repertoire activity. Materials and methods. Thiotriazoline, decamethoxinum, model mixture. The studies were carried out by agar diffusion (well method) to study antimicrobial activity. Model mixtures with decamethoxinum were made from 0.5 to 5 mg; thiotriazoline – 200 mg. Antimicrobial activity of these model mixtures was carried out. Results. The model mixture of thiotriazoline and decamethoxinum in antimicrobial and fungicidal action was significantly superior to decamethoxinum by 54 % in the degree of growth inhibition of S. aureus, by 120 % in the degree of growth inhibition of E. coli, by 57 % in the degree of growth inhibition of P. aeruginosa, and by 108 % in the degree of growth retardation of C. albicans at 106 CFU/ml of medium. Conclusion. The model mixture of thiotriazoline and decamethoxinum exhibits high antimicrobial and fungicidal activity.

Particular attention is paid to the release of the active ingredients of drugs in the form of tablets. Therefore, we have developed a method for determining the dissolution test, for the original drug Hypertril. The purpose. To develop a methodology for dissolution test for Hypertril tablets with an active substance content of 20 mg using the HPLC method. Materials and methods. In the studies we used Hypertril tablets with an active substance content of 20 mg, obtained in the Standardization and Drug Technology Laboratory at the Pharmaceutical Chemistry Department of ZSMU. A standard sample of the hypertril substance was received from the State Enterprise “Chemical Reagents Plant” (Kharkiv, Ukraine). We used high-performance liquid chromatograph Bishoff with an UV detector for studies. During the dissolution test of the Hypertril tablets, a device with a blade from the company Pharma Test PTWS 120D, Germany, was used. Results. As a result of the conducted studies, the chromatograms were obtained. Having analyzed the chromatograms, we proved that the method is highly sensitive and accurate and can be used to determine the dissolution test. The obtained study results showed that the amount of the active substance that passed into the solution from the Hypertril tablets after 45 minutes and is from 91.2 to 99.6 %, that meets the requirements of the State Pharmacopoeia of Ukraine. Conclusions. In the course of study, we developed a method for carrying out the dissolution test for Hypertril tablets with an active substance content of 20 mg using the HPLC method. The study results confirm that the developed method is accurate and reliable.