The price factor is an important element when using a therapy management, that is complicated by the deterioration in the socio-economic situation of Ukrainians and the National Health Care system in the middle of war. The aim is to examine patients’ willingness-to-pay for topical antifungal drugs (TAFDs) taking into account their differing consumer characteristics in order to justify the economic component in the development and pharmaceutical market introduction of national drugs and to formulate recommendations for improving the level of pharmaceutical care for patients with fungal skin diseases. Materials and methods. The results of a sociological TAFDs’ consumer survey were used as the basic study material. In this study, the methods of information retrieval, summarizing, formalizing, questioning, van Westendorp’s Price Sensitivity Meter (PSM) were used. The respondent geography covered the Zaporizhzhia, Dnipropetrovsk, Cherkasy, Poltava, Ivano-Frankivsk, Kyiv, Odesa regions. Results. A total group analysis of price sensitivity was conducted including 8 TAFDs with calculation of optimal (OPP), indifferent (IDP), minimum (MCP) and maximum (MEP) respondents’ willingness-to-pay prices. The same prices were subsequently calculated in the intra-group price analysis of respondents with different income levels and experience in drug therapy for fungal skin diseases. The cumulative distribution of respondents was graphed at three stages of the study calculations for the identified subgroups (64 graphs in total). Conclusions. The van Westendorp’s Price Sensitivity Meter (PSM) has been used to examine patients’ willingness-to-pay for topical antifungal drugs considering their different consumer characteristics: final dosage form – gel, ointment, cream, solution, spray; combined / monocomponent. At the same time, opinion of patients with different levels of income and experience of drug therapy for fungal skin diseases has been sought. Based on the studies, the economic component and the promising form of a new antifungal drug for topical use (pharmacy or industrial production) – a spray or gel with a price in the range of UAH 181–230 have been justified.

The market of medicinal products in Ukraine tends to constant changes. The dynamics of the pharmaceutical market, especially in today’s conditions of uncertainty, completely depend on the income of the population. For the implementation of new trajectories of improvement of pharmaceutical care, there is a study of the processes of consumer preferences of the patient / buyer to the pharmaceutical product, followed by the formation of consumer values and price sensitivity. The aim of the work was to determine the price sensitivity of consumers in order to establish the consumer value of topical antifungal agents in the medicinal form “gel”. Materials and methods. The van Westendorp method (PSM – price sensitivity measurement) was used in the study. The material for conducting the study was the available information sources indicating the list of drugs for the prevention and treatment of mycosis of the feet in the soft dosage form “gel” with only antifungal activity and with antifungal activity and additional antibacterial action, azole derivatives (websites-aggregators: apteka24.ua/uk/, doc.ua, tabletki.ua, compendium.com.ua/uk/, likie.ua, liki24.com, helsi.me/liki) and the results of the responses of respondents-consumers based on processing of a previously created questionnaire. Results. For each medicinal product with a gel dosage form with antifungal action only and with antifungal and additional antibacterial action, azole derivatives, we have built graphs of the cumulative distribution of respondents, calculated the point values of the minimum (MCP), maximum (MEP), optimal (OPP) and indifferent price (IDP) that respondents are willing to pay for an antifungal product. It was determined that, according to the generalized opinion of the respondents, the highest OPP and IDP and the corresponding range of acceptable prices (OPP-IDP) are for combined forms of medicines that have not only antifungal action but also additional antibacterial activity. At the second stage of the study, an intra-group price analysis was conducted. The respondents were divided into 2 groups based on the consumer income characteristic. The next stage of the study included an intra-group price analysis based on the consumer characteristic “sick / not sick”. Conclusions. As a result of the analysis of the concept of trust marketing in the study of price sensitivity for the study of consumer value of antifungal topical agents in the gel dosage form with antifungal activity only and with antifungal activity and additional antibacterial action, azole derivatives, the price sensitivity of consumers was determined and lists of the most attractive studied drugs in terms of consumer value were formed.

Nowadays, cancer remains one of the main causes of death worldwide. Statistical data from various literary sources indicate that more than 130,000 people in Ukraine receive this diagnosis as a sentence every year. Cancer can affect any organs of the human body and, over time, the entire organism. In 2024, the agency of the World Health Organization on cancer and the International Agency of Cancer Research published the latest statistical estimates of this pathology in a global format, where prostate cancer is among the five most common oncological pathologies and takes the fourth place. Oncological diseases are one of the priority areas of healthcare development in accordance with the Order of the Ministry of Health of Ukraine No. 1832 dated 07.10.2022 “On Approval of Priority Areas of Healthcare Development for 2023–2025”. It was this fact that determined the choice of the direction of this research in the matter of finding information on the provision of pharmaceutical care, namely the use of a drug – a rectal suppository for the treatment of prostate cancer. The aim of the work is to carry out a bibliometric analysis and further generalize the data of the scientific literature to study the prognostic value and features of the prescription of suppositories in the treatment of prostate cancer. Materials and methods. The data search was conducted in the PubMed electronic database using the following key terms: “prostate cancer and suppositories”, “prostate cancer”. To monitor and analyze international scientific research, with the help of visualization tools and modern SciVal citation metrics using the online platform, bibliometric analysis can be performed. Using the VOSviewer functional program, bibliometric networks were constructed and visualized. Results. A map of the relationships between the most used keywords on the topics of “prostate cancer” and “prostate cancer and suppositories”, grouped into clusters for the period from 1986 to 2024, was built. The clustering of the most used keywords on the subject of “prostate cancer” for the specified period is summarized. According to the bibliographic analysis, interest in the above topic was highest in 2014 and 2021. Conclusions. According to the bibliographic analysis, the interest in the subject of the patients’ treatment with prostate cancer disease continues to grow from 1998 up to the present. The analysis of publication activity using the visualization tool of bibliometric networks VOSviewer for the period from 2014 to 2024 for the key words “prostate cancer” has shown the presence of 14 clusters. The largest cluster is devoted to modern methods of prostate cancer treatment, studies of gene rearrangement, target therapy, carcinogenesis.

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.

Cancer is still one of the leading causes of death worldwide. Statistical data show that more than 130,000 people in Ukraine receive this diagnosis as a sentence every year. Cancer can affect any organ and eventually the whole body. In most cases, cancer is a tumor affecting epithelial, mucous, muscle, fat, and bone tissues. Also, processes related to malignant formations can occur in the blood and lymph. The main mechanism that triggers the process of formation of neoplasms is a violation of growth and, accordingly, cell division. They begin to grow uncontrollably, multiply, and can also migrate, spreading to nearby tissue structures, and later degenerate into atypical (malignant) ones. Cancer is one of the most life-threatening diseases. Literature data show that more than 90 % of cancer patients die due to chronic metastases. Cancer therapy involves the use of drugs that block the growth and spread of cancer cells by affecting certain molecular structures involved in the growth, progression, and spread of cancer. The diversity of the use of means for cancer therapy, namely, hormone therapy, the use of angiogenesis inhibitors and apoptosis inducers, has provided scientists with various options for finding effective means to fight this disease. Aim. The aim of the work is the analysis and systematization of new data on the anticancer activity of 1,2,4-triazole derivatives and the selection of the most promising directions for further scientific research based on the results of the analysis. Materials and methods. The study employed various methods, including analysis, information search, bibliosemantic analysis, descriptive techniques, and generalization. Research materials primarily comprised literary sources containing information on the promising array of new biologically active compounds, particularly 1,2,4-triazole derivatives, known for their targeted anticancer properties. Results. A literature search was carried out, 1,2,4-triazole derivatives with antitumor activity were analysed, characterized and summarized. Based on the study of available information and conducting an information and patent search, it was established that the market of Ukraine is insufficiently saturated with 1,2,4-triazole-containing drugs with anticancer activity of domestic production. It was determined that the development of new effective drugs based on 1,2,4-triazole and potential drugs with clearly directed anticancer activity requires a systematic approach both in conducting synthetic tests and screening new compounds for further structural optimization of molecules. Conclusions. The analysis of scientific literature in recent years devoted to the study of the anticancer activity of 1,2,4-triazole derivatives convincingly proves the prospect of further research in this direction. Numerous publications indicate the possibility of constant improvement of molecules with regard to the presence of anticancer activity. Domestic and foreign authors have clearly and argumentatively proven the perspective of the scientific direction for the creation of new original drugs to combat various oncopathologies.

In Ukraine, there is a targeted scientific and technical program for the development of technologies for the creation of modern domestic medicines. One of the most promising ways in this program is the development and implementation of drugs to combat various multi-resistant diseases. The study of the effect of biologically active substances on the structural components of mushrooms determines the possibility of finding new highly effective antifungal compounds. The aim of the work was the analysis and systematization of existing new data on the antifungal activity of a number of 1,2,4-triazole derivatives and the selection, based on the results of a comprehensive analysis of literary sources, of promising directions for further scientific research. Methods used: information search, synthetic, analytical, bibliographic, descriptive, generalization. The research materials were literary sources that contain information on the antifungal activity of a number of 1,2,4-triazole derivatives. The authors repeatedly claim that 1,2,4-triazole derivatives with a 1,2,3-benzotriazin-4-one fragment show significant antifungal potential against Candida albicans and Cryptococcus neoformans. Foreign researchers proved that a series of triazole-containing isoxazole compounds has antifungal activity against eight fungi pathogenic to humans. Another team of scientists proved the high antifungal activity of pyrimidine derivatives of 1,2,4-triazole. Domestic authors found that the modeling of 1,2,4-triazole due to the introduction of a Sulfur atom and subsequent transformations by this atom lead in many cases to the emergence of antifungal activity in molecules. Scientists of the Zaporizhzhya State Medical and Pharmaceutical University have proven the high antifungal activity of some amino derivatives of 1,2,4-triazole. The analysis of scientific publications dedicated to the study of antifungal properties of 1,2,4-triazole derivatives in recent years proves the indisputable prospect of finding new biologically active agents among substituted 1,2,4-thiazoles. Numerous publications indicate that in recent years, new molecules have appeared in a number of 1,2,4-triazole derivatives that have antifungal properties. The authors clearly and argumentatively proved the perspective of the direction of creating new original drugs for the treatment of various fungal pathologies.

Вступ. Актуальність дослідження спрямовано на розробку технологічних схем отримання сучасних лікарських засобів (ЛЗ) для місцевого лікування ран з використанням похідних 1,2,4-триазолу. Такі лікарські засоби включають мазі та ранові гідрогелеві пов'язки вітчизняного виробництва, які мають комплексну дію, забезпечуючи антибактеріальні, анестезуючі, протизапальні та антимікробні властивості. Лікування травм та інфекцій вразливих ділянок залишається актуальною медичною проблемою. Мета роботи – проведення досліджень, спрямованих на обґрунтування рецептурного складу крему, вивчення технологiчних аспектів та особливостей виготовлення, аналiзу м’якої лiкарської форми субстанції 2-(((3-(2-флуорофеніл)-5-меркапто-4Н-1,2,4-триазол-4-іл)іміно)метил)фенолу. Матеріали та методи. Температури плавлення визначаються капілярним методом в «Stanford Research Systems Melting Point Apparatus 100» (SRS, США). Використані реагенти були придбані у Sigma-Aldrich (Merck). Термогравіметричний аналіз проводили за допомогою дериватографа Q-1000 від системи Ф. Паулік, І. Паулік, Л. Єфдей з платиново-платинородієвою термопарою. Для контролю якості розробленого засобу застосовували методики та рекомендації розділу "М'які лікарські засоби для місцевого застосування" (ДФУ, I видання, с. 507–511), а також ДСТУ 4765:2007 «Креми косметичні. Загальні технічні вимоги». Для хроматографічних експериментів використовувалася система ВЕРХ-МС: Agilent 1260 Infinity, включаючи дегазатор, бінарну помпу, автосемплер, моночетверний МС-детектор Agilent 6120 з електроспрей-іонізацією API-ES). Інтерпретацію спектрів здійснював програмний комплекс OpenLAB CDS. Результати. При хроматографуванні за зазначених умов час утримування піку АФІ має становити близько 3,8 хв. Обґрунтуванні умови кількісного хроматографічного визначення АФІ. Вивчено вплив температури на поведінку 2-(((3-(2-флуорофеніл)-5-меркапто-4Н-1,2,4-триазол-4-іл)іміно)метил)фенолу за допомогою методу термогравіметрії. Аналіз термогравіметрії 2-(((3-(2-флуорофеніл)-5-меркапто-4Н-1,2,4-триазол-4-іл)іміно)метил)фенолу (рис. 1) вказує на те, що точка плавлення відзначається у проміжку 207–209 ºС, проте втрата маси спостерігається лише при нагріванні субстанції вище 223 ºС. Проведений аналіз також показує зменшення температури плавлення 2-(((3-(2-флуорофеніл)-5-меркапто-4Н-1,2,4-триазол-4-іл)іміно)метил)фенолу при її включенні в основу. Втрат маси зразка не відзначено в діапазоні до 250 ºС, і спостерігається значний ендотермічний ефект при температурі 126 ºС, що вказує на високий ступінь зв’язування води та компонентів масляної фази обраними емульгаторами. На основі проведених біофармацевтичних та технологічних досліджень розроблено склад та технологію крему і складено технологічну схему виробництва. Висновки. В результаті термогравіметричного аналізу визначено оптимальну температуру введення компонентів у розроблений крем. Обґрунтуванні умови кількісного хроматографічного визначення АФІ. В рамках дослідження були уточнені технологічні параметри виготовлення крему, включаючи 2-(((3-(2-флуорофеніл)-5-меркапто-4Н-1,2,4-триазол-4-іл)іміно)метил)фенол. На основі отриманих даних розроблено оптимальну технологію та створено блок-схему технологічного процесу для нового медичного засобу, призначеного для лікування грибкової інфекції.

The trend of increasing incidence of skin diseases of various etiologies and the frequency of complications caused by them (dermatitis, allergies, secondary infections, eczema, trichophytosis, dermatophytosis, dermatomycosis, etc.) is increasing in Ukraine. Nowadays the important problem is the development of new domestic effective medicines to combat this pathology. The general market of veterinary drugs, feed additives of finished feed, and premixes was investigated, and the place of drugs used to combat fungal diseases of animal skin was determined to identify the current state and prospects for the development of domestic veterinary drugs (DVD) production. It is established that the studied range of the market saturation structure of veterinary drugs, feed additives, finished feeds, and premixes have significant competition in the pharmaceutical market of Ukraine from foreign manufacturers. The range of effective domestic medicines for the treatment of fungal skin diseases of animals based on domestic substances is very minor, so there are prospects for the introduction into production and further promotion of new effective drugs in this area on the domestic market. The aim of the work is to determine the current state and prospects for the development of the production of national veterinary medicines for the treatment of fungal diseases of animal skin based on the study of the structure of the general market for veterinary drugs, feed additives, finished feed, premixes and determination of their market share. Materials and methods. The following methods (synthetic, analytical, information search, descriptive, generalization) were used in the work. The research materials were literary sources that contain information on the structure of the veterinary market of antifungal and antimicrobial drugs and the “List of Registration of Veterinary Drugs, Feed Additives, and Finished Feeds” as of July 21, 2022. Results. According to the above List, it was found that as of 21.07.2022, 6574 trade names of these products were registered on the Ukrainian market of veterinary medicines, feed additives, finished feed, and premixes. 5097 (77.53 %) of which were supplied by foreign manufacturers, the rest – 1497 (22.47 %) were products of domestic manufacturers. The geography of suppliers is represented by 47 countries, including Ukraine. France, Poland, and Germany remain the leaders in terms of the number of registered items of drugs, feed additives, finished feeds, and premixes. Based on the marketing analysis, it was found that in terms of dosage forms, this market is overly heterogeneous and is represented by 31 dosage forms, which are powders, liquid, solid, soft, and gaseous forms by consistency. It has been proved that a small assortment of antifungal DVDs makes it possible to saturate this segment of the pharmaceutical market not only with imported drugs, but also to find opportunities for the creation and introduction of fundamentally new antifungal DVDs to the domestic market. Conclusions. The development and introduction of new antifungal drugs to the market for further use in the treatment of skin diseases are important. It will contribute to improving the effectiveness of prevention and treatment of the above diseases and will allow the offering of effective innovative pharmacotherapeutic drugs to domestic veterinary practice.

Вступ. При цілеспрямованому синтезі нових молекул в їх структури досить часто включають фрагмент 1,2,4-триазолу. Його невеликі розміри, достатня розчинність, висока реакційна здатність та незначна токсичність позитивно впливають на властивості нових сполук, фрагментом яких є 1,2,4-триазол. 1,2,4-Триазол входить до складу структур відомих противірусних (рибавірин), протигрибкових (флуконазол), снодійних (триазолам) препаратів тощо. Відомо, що 4-((5-(децилтіо)-4-метил-4Н-1,2,4-триазол-3-іл)-метил)морфолін є активним фармацевтичним інгредієнтом (АФІ) ветеринарного препарату «Ветмікодерм», зареєстрованого в Україні у 2022 році. Препарат виявився ефективним засобом для лікування дерматологічних захворювань різної етіології у домашніх тварин. Мета роботи – розробка нового, ефективного та надійного способу одержання 4-((5-децилтіо)-4-метил-4-Н-1,2,4-триазол-3-іл)метил)морфоліну шляхом оптимального підбору вихідних реагентів та умов одержання кінцевого продукту за участю мікрохвильового випромінювання. Матеріали та методи. Вихідні реагенти для синтезу були закуплені у Sigma (Aldrich). ІЧ-спектри знімались на спектрофотометрі Bruker Alpha в області 7500–400 см-1 із використанням методу нанесення рідини на плівку. Газовий хроматограф Agilent 7890B з мас-спектрометричним детектором 5977B. Для ідентифікації компонентів була використана бібліотека мас-спектрів NIST14. Система мікрохвильового синтезу Milestone Flexi Wave. Для визначення температури плавлення використовували відкритий капілярний метод на приладі OptiMelt MPA100. Результати. Мікрохвильові умови синтезу вихідної сполуки оцінювали за різних умов: час опромінення в режимі потужності (600 і 500 Вт), так і в різному проміжку часу проходження реакції. Цікаво, що при спробі в режимі потужності при будь-якому налаштуванні протягом 5–15 хвилин було виявлено мало продукту реакції. Через 20, 25, 30 хвилин відбирали із реакційного середовища проби і аналізували за допомогою газової хроматографії. Оптимальними умовами для проведення синтезу при мікрохвильовому випромінюванні, а саме потужність 600W та час – 30 хвилин, дозволяють отримати сполуку 4-((5-децилтіо)-4-метил-4Н-1,2,4-триазол-3-іл)метил)морфоліну зі значними виходом 97% для промислового виробництва зазначеної субстанції. Висновки. Нові умови забезпечують підвищення виходу кінцевого продукту при одночасному зниженні енерговитрат на його одержання та підвищенні продуктивності способу, що обумовлює зниження собівартості кінцевого продукту за умови проведення синтезу при мікрохвильовому випромінюванні, а саме потужність 600W та час – 30 хвилин.

Мета роботи – визначення можливої ембріотоксичної, фето- та ембріолетальної дії сполуки 4-((5-(децилтіо)-4-метил-4H-1,2,4-триазол-3-іл)-метил)морфоліну у постнатальному періоді. Матеріали та методи. Досліди проводилися на щурах лінії Вістар масою 170-215 грам при пероральному введенні зазначеної сполуки. Субстанція вводилася щурам внутрішньошлунково один раз на добу, в один й той же час за допомогою спеціального зонду в дозах 18,40,90 мг/кг. Тестування проводилися на клінічно здорових, інтактних, статевозрілих білих щурах лінії Вістар, яких утримували в оптимальних умовах. Перевірка ембріотоксичної дії 4-((5-(децилтіо)-4-метил-4H-1,2,4-триазол-3-іл)-метил)морфоліну проводилася на білих щурах на 20-21 добу вагітності. У ці терміни підраховувались показники ембріональної смертності після евтаназії і розтину самиць. Для виведення показника смертності перед імплантацією обчислювалася різниця між кількістю місць імплантації і визначалося, яку частку (у %) склала ця цифра від числа імплантацій (прийнятих за 100%). При статистичній обробці за одиницю спостереження приймали послід, тобто результати, отримані при розтині однієї самиці. Порівняння достовірності цифрових даних, отриманих в досліді і на контролі, проводилося методами непараметричної статистики з використанням критерію Вілкінсона-Манн-Вітней. Результати. Аналіз отриманих результатів показує, що в першій серії дослідів після щоденного одноразового внутрішньошлункового введення загинуло 9 ембріонів. У другій серії загинуло 11 ембріонів, а в третій серії 45 ембріонів. У контрольній групі (четверта серія) загинуло 2 ембріони. В результаті проведених досліджень встановлено, що паралельне введення 4-((5-децилтіо)-4-метил-4-Н-1,2,4-триазол-3~іл)метил)морфоліну в дозах 18 і 40 мг/кг упродовж 56 днів самцям білих щурів істотно не впливало на приріст маси тіла тварин. Результати вивчення впливу 4-((5-децилтіо)-4-метил-4-Н-1,2,4-триазол-3- іл)метил)морфоліну на частоту еструсів упродовж періоду спарювання (14 днів), вагітність і кількість плодів лабораторних тварин, що вижили показали, що за щоденного введення 4-((5-децилтіо)- 4-метил-4-Н-1,2,4-триазол-3-іл)метил)морфоліну в дозах 18 і 40 мг/кг істотної дії на перебіг естрального циклу білих щурів не виявлено, а частота еструсів була в межах 3,0-3,8. Встановлено, що самки білих щурів популяції Вістар вагітніли в 93 % випадків в контрольній групі тварин, у 96 % тварин, яким вводили 18 мг/кг, і в 98% випадків в групі тварин, які отримували 4-((5-децилтіо)-4-метил-4-Н-1,2,4-триазол-3-іл)метил)морфолін в дозі 40 мг/кг. Аналіз представлених даних показав, що маса тіла плодів як самок, так і самців дослідних груп не мали достовірних відмінностей із показниками маси тіла плодів контрольної групи. Зовнішній огляд тіла і кінцівок плодів не виявив аномалій розвитку ні в контрольній, ні в дослідних групах. Результати всіх дослідів були оброблені за допомогою методів математичної статистики. Для кожної величини визначали середню арифметичну і стандартну помилку. Оскільки багато розподілів вірогідності отриманих величин відрізнялися від нормального, для оцінки достовірності відмінності між ними був використаний непараметричний критерій Ван-дер-Вардена. Висновки. Математична обробка отриманих даних показала, що з жодного із досліджених показників не спостерігається статистично значимих відмінностей між результатами контрольних і дослідних серій. Таким чином, фізичний розвиток і показники дозрівання нервової діяльності потомства щурів, що отримували під час вагітності 4-((5-децилтіо)-4-метил-4-Н-1,2,4-триазол-З-іл)метил)морфолін, не відрізнялися істотно від потомства контрольних тварин. Не було виявлено істотних відмінностей і при дослідженні їх здатності до навчання та пам`яті. Слід зазначити, що 4-((5-децилтіо)-4-метил-4-Н-1,2.4-триазол-3-іл)метил)морфолін, в ефективних дозах, не має ембріотоксичного ефекту.

Synthetic biologically active compounds are the active pharmaceutical ingredients of various dosage forms that are widely used in both human and veterinary medicine. Nowadays the development of new effective antimicrobial and antifungal drugs remains a actual problem. This fact has a reasoned explanation in connection with the increase in infectious diseases of microbial and fungal etiology and the ever-growing resistance of microorganisms and fungi to various drugs. The aim of this research was to develop and validate a new spectrophotometric method for the quantitative determination of 4-((5-(decylthio)-4-methyl-4-H-1,2,4-triazol-3-yl)methyl)morpholine in 7% ointment by intrinsic absorption. At the stage of development of the quantitative determination method, the solvent was selected based on the solubility of the active substance. According to the data provided, 4-((5-(decylthio)-4-methyl-4-H-1,2,4-triazol-3-yl)methyl)morpholine is insoluble in water, but soluble in ethanol, methanol, isopropanol, dioxane, and dimethyl sulfoxide. Ethanol was chosen as the most accessible and less toxic solvent for the development of this method. Studied 4-((5-(decylthio)-4-methyl-4-H-1,2,4-triazol-3-yl)methyl)morpholine dissolved in ethanol is introduced into the ointment base as a solution. The quantitative content of substances subject to chemical control in soft dosage forms should be between 90% and 110% of the nominal content. On this basis, the maximum permitted analytical uncertainty can be determined, which is 3.20. During the procedure the main validation characteristics were determined, such as: linearity, precision, accuracy and robustness. Thus, a new sensitive, economical and easy-to-use spectrophotometric method for the quantitative determination of 4-((5-(decylthio)-4-methyl-4-H-1,2,4-triazol-3-yl)methyl)morpholine in a soft dosage form for external use (7% ointment) by the intrinsic absorption method was developed. According to the main validation characteristics (linearity, precision, accuracy and robustness), the proposed method is valid and meets the requirements of the State Pharmacopoeia of Ukraine.

Вступ. Не зважаючи на очевидні досягнення вітчизняної та зарубіжної фармацевтичної науки в розробці лікувальних і профілактичних прийомів при терапії гінекологічних патологій, у деяких тварин спостерігається тенденція зростання даних захворювань. Тому своєчасним питанням стало вивчення асортименту ветеринарних препаратів для лікування акушерсько-гінекологічних захворювань, представлених на ринку України. Проведений аналіз показав, що у ветеринарній практиці для лікування ендометритів знаходять застосування багато лікарських форм, що вводяться внутрішньоматково (розчини, емульсії, суспензії, палички, таблетки, брикети, супозіторії, мазі, аерозолі), серед яких найбільш поширеними є тверді форми. Вітчизняний фармацевтичний ринок ветеринарних лікарських засобів не має напруги в таких препаратах. Тому, створення нової м`якої лікарської форми - вагінальних супозиторіїв є актуальним питанням сьогодення. Мета роботи – розробка технології виготовлення нового ветеринарного лікарського засобу – супозиторіїв з трифузолом. Матеріали та методи. Для розробки технології виготовлення лікарського засобу використано бібліометричний метод, а саме було проведено аналіз публікацій в науково-практичних виданнях, огляд наукової літератури, специфікацій обладнання, вимог ГНД (галузевий нормативний документ) 09-001-98, ДФУ (Державна фармакопея України) та керівних Настанов МОЗ України. Результати. До складу виготовлених вагінальних супозиторіїв входить піперидиній 2-[5-(2-фурил)-4-феніл-1,2,4-триазол-3-ілтіо]ацетат, натрій лаурилсульфат, пропіленгліколь, поліетиленоксид-400, проксанол-268 та твін-80. Розроблена робоча рецептура вагінальних супозиторіїв. Технологічний процес промислового виробництва вагінальних супозиторіїв з трифузолом включає в себе п`ять стадій. Висновки. Запропонована технологія виготовлення супозиторіїв вагінальних з піперидиній 2-[5-(2-фурил)-4-феніл-1,2,4-триазол-3-ілтіо]ацетату і натрій лаурилсульфату надає препарату високі фармакотехнологічні, реологічні та біофармацевтичні властивості.

It is well known, that 1,2,4–triazole derivatives have a wide range of biological properties, showing little toxicity. Original modeling of 1,2,4-triazole derivatives allows obtaining new molecules with unique properties. Such purposeful changes in molecules are popular among many scientists because they make it possible to obtain compounds with «improved» properties. Such a compound was the substance (4-((5-(decylthio)-4-methyl-4H-1,2,4-triazol-3-yl)-methyl)morpholine with the prospect of creating a mild medicinal product – liniment «Vetmikoderm». The main advantage of these medicinal forms is a low traumatic effect on damaged tissue, creating maximum contact with the wound surface, etc. It has been proven, that the antimicrobial agents available on the veterinary drugs’ market, including those ones in the form of ointments, gels and liniments, are characterized by the fact that they do not always stimulate tissue regeneration processes. Medicines with the ability to improve wound healing, as a rule, have minor antiseptic properties. Under these circumstances, the search, development and introduction of the medicines that have antimicrobial and antifungal action is an extremely urgent issue of modern veterinary medicine. The aim of our research was to study the technological aspects and manufacturing features, the substantiation of the composition, the analysis of the soft medicinal form of the drug «Vetmikoderm». During the research, the appearance, transparency, and thickness of the drug were determined. APHI identification was carried out with the determination of its content by the gas chromatography’s method. The external standard method was used. Microbiological purity (bacteria, yeast and mold fungi (in total), the presence of bacteria of the Enterobacteriaceae family, Staphylococcus aureus and Pseudomonas aeruginosa) was determined in accordance with the requirements of the SPHU by the membrane filtration method. Sterile soy–casein agar was used to determine the total number of aerobic bacteria. Determination of harmlessness was carried out according to the «abnormal toxicity» indicator. On the basis of the conducted research, the technological aspects and manufacturing features, substantiation of the composition, quantitative and qualitative analysis of the «Vetmikoderm» liniment were determined, which ensures the possibility of the medicinal form’s obtaining in industrial conditions. The proposed methods of the medicinal form’s analysis are characterized by sensitivity and reproducibility.

The main direction of the development of the education system in Ukraine is the introduction of European standards, technologies, norms, and perspectives to ensure competitiveness in the market of European education services. The study aimed to highlight modern approaches to the standardization of higher education in the context of shaping professional competences of future pharmacists, to identify peculiarities and possibilities of applying a systemic approach to the development of a higher education standard for the specialty of 226 Pharmacy, Industrial Pharmacy of the second (master’s) level. The research materials consisted of references containing information on the development, approval, and implementation of higher education standard. The following methods were used in the study: synthetic, analytical, information search, descriptive, and generalization. The pharmaceutical industry is socially significant, and the specialty of 226 Pharmacy, Industrial Pharmacy, as well as all the specialties in the field of study 22 Health, are regulated. Therefore, professionals in this field should possess integrated knowledge and skills, be able to solve complex tasks and problems in the field of pharmacy and healthcare, both in practice and during the learning process. This involves conducting research, implementing innovations, and is characterized by uncertain conditions and requirements. A modern approach also involves the use of highly efficient technologies in the national and international educational and scientific environments, which ensure the preparation of competitive, highly qualified pharmaceutical professionals with moral and spiritual values, social responsibility, and community orientation. They are capable of providing quality pharmaceutical care to people and possess «soft skills». Upon the development of the approved higher education standard for the specialty of 226 Pharmacy, Industrial Pharmacy by the Ministry of Education and Science of Ukraine, the educational and professional programs Pharmacy and Perfume and Cosmetic Technologies were revised, and a list of competences as well as program learning outcomes for future pharmaceutical professionals was specified. These were aligned with the demands of the labor market and a professional-oriented approach, based on the concept of competences for a modern pharmacist and the variable components of educational and professional training programs

The modern market of medicines in Ukraine has the dynamics of constant development. At the same time, the dynamics of the pharmaceutical market depend entirely on the welfare of the population. Current features of quarantine restrictions have caused a number of distortions in drug consumption. Thus, after the introduction of quarantine in March 2020, part of the population panicked, which forced them to stockpile vital goods. At this time, there was a significant increase in sales of drugs, including antiviral, antiseptic, and disinfectant activity. The dynamics of drug balances on the shelves reached +50 %. However, there was a sharp decline in consumption between June-October 2020 and April 2021 due to the full effect of quarantine restrictions and March-April 2022 due to martial law in Ukraine. Today, the rate of purchases and balances of medicines on the shelves of pharmacies exceeds the rate of growth of their sales. The aim of the work is to conduct research and provide a description of the range of the national market of domestic 1,2,4-triazole-containing drugs. Materials and methods. The following methods were used in the work: analytical, information retrieval, descriptive, and generalization. The materials of the research were literature sources that contain information on the registration of domestic 1,2,4-triazole-containing drugs in Ukraine at present. Results. The search, analysis, characterization, and generalization of domestic drugs – derivatives of 1,2,4-triazoles were carried out. It was established that the Ukrainian market was moderately saturated with 1,2,4-triazole-containing drugs of domestic production based on the study of available information and scientific research. The drugs have a fairly wide range of applications in medicine, have different mechanisms of action, belong to different pharmacotherapeutic groups, and were used in veterinary practice and the agro-industrial economy. Conclusions. Elaboration, analysis, systematization, comparison, and generalization of modern sources of information indicated a fairly high biological activity of 1,2,4-triazole derivatives, a wide range of applications, and moderate saturation of the national market with 1,2,4-triazole-containing drugs.

The introduction of new domestic highly effective and safe medicines into medical and veterinary practice is an important task of modern pharmaceutical science. Continuation of the search and conduct of research to bring the biological activity of 1,2,4-triazole derivatives is one of the promising areas of such activity. At this stage of research, it is known that such 1,2,4-triazole derivatives as 4-((5-(decylthio)-4-methyl-4H-1,2,4-triazole-3-yl)methyl)morpholine and 5-(2-fluorophenyl)-4-((4-bromophenyl)ylidene)amino-1,2,4-triazole-3-thiol have a wide spectrum of biological activity. Interest for further thorough research is precisely the antimicrobial and antifungal effects. The introduction into medical and veterinary practice of newly created drugs for the treatment of fungal diseases on the skin of animals requires further studies of the properties of these compounds and their mixtures. The aim of the work was to determine the indicators of the morphological composition of the blood of animals and individual biochemical indicators when using a preparation with a mixture of two active compounds: 4-((5-(decylthio)-4-methyl-4H-1,2,4-triazole-3-yl)methyl)morpholine and 5-(2-fluorophenyl)-4-((4-bromophenyl)ylidene)amino-1,2,4-triazole-3-thiol in thistle seed oil. Materials and methods. The material for laboratory research was serum and blood plasma, stabilized by adding trilon-B, tissue biopsy. Indicators were determined in healthy animals and experimentally diseased animals on the third and tenth days after the onset of the disease according to the generally accepted method. During the research, in the course of treatment, general clinical examinations and local examinations of purulent wounds were carried out, as well as blood samples taken from each head of the sheep in the experimental and control groups before the beginning and on the third and tenth days of the experiment. The purulent-inflammatory process was caused by injuring the soft tissues in the groin area on the left side, with the help of a specially made template, followed by dilation of the muscle tissue with an angiotrip and implantation of aerobic-anaerobic surgical infection cultures taken from the bed. The resulting wounds had the following dimensions: 10 cm in length, 1 cm in width, and 2 cm in depth. As early as 24 hours after induction of experimental purulent inflammation, characteristic clinical signs appeared in sheep. The general condition of all 12 animals was somewhat depressed, the appetite was normal. The body temperature was in the range of 38.6–40.3 °C, the pulse was 76–82 beats, and the frequency of respiratory movements was 16–18 per minute. The frequency of scar contractions was 3–6 times in 2 minutes. During the examination, slight swelling was also found in the area of the wound and its edges. There was a small amount of serous-bloody exudate on the surface of the wound. On the 3rd day, the maximum manifestation of clinical signs of acute purulent inflammation was observed in all 12 sheep. In particular, the general condition of the animals is depressed. A partial loss of appetite was observed. General temperature 40.4–40.8 °C, pulse 75–82 beats, frequency of respiratory movements 18–22 per minute. The frequency of scar contractions was 3–6 times in 2 minutes. Visible mucous membranes are pale pink in color. When pressing on the area of the wound, a serous-purulent exudate was observed. Results. Laboratory indicators of blood and tissue biopsy that are more optimal than in the control group confirm positive changes in the clinical status of the animals in the experimental group. The use of a potential preparation with a mixture of two active compounds: 4-((5-(decylthio)-4-methyl-4H-1,2,4-triazole-3-yl)methyl)morpholine and 5-(2-fluorophenyl)-4-((4-bromophenyl)ylidene)amino-1,2,4-triazole-3-thiol in thistle seed oil leads to faster healing of purulent wounds, in relation to the use of “Vetmikoderm” liniment (control group). The difference in the areas of the wound defect on the 10–11th day was 17.5 %. Clinical studies were confirmed by laboratory studies and wound biopsies. Conclusions. The preparation with two compounds: 4-((5-(decylthio)-4-methyl-4H-1,2,4-triazole-3-yl)methyl)morpholine and 5-(2-fluorophenyl)-4-((4-bromophenyl)ylidene)amino-1,2,4-triazole-3-thiol had pronounced pharmacokinetic parameters and was bioavailable.

Today, 1,2,4-triazole derivatives are a promising class of organic compounds. This is caused, first of all, by the possibility of various chemical modifications of the 1,2,4-triazole fragment due to the addition of typical pharmacophores, which contributes to the expansion of the new molecules’ arsenal. A significant number of the 1,2,4-triazole derivatives show biological properties, that postively affects the further process of the most promising substances’ introduction. The aim of the work was to analyze the influence of various functional substituents of the new 1,2,4-triazole derivatives on the indicators of the mentioned compounds’ biological activity. Literature sources containing information on the influence of various functional substituents of the new 1,2,4-triazole derivatives on the indicators of these compounds’ biological activity became the research materials. Methods were used in the work: analytical, bibliosemantic information search, generalization. Triazoles and their heterocyclic analogues are compounds that contain a certain amount of Nitrogen atoms in their composition, showing the properties of typical pharmacophores. Their derivatives are easily synthesized and can be transformed into various biologically active molecules. Information on the 1,2,4-triazole derivatives’ chemical modeling, which allows for purposefully obtaining compounds with the necessary biological properties, taking into account the toxicity indicators of new molecules, has been analyzed and summarized. The authors have proved, that the gradual and predicted introduction of various substituents into the molecule of 1,2,4-triazole derivatives leads to the appearance of new types of biological activity, in some cases it gives an increase in already existing activity indicators. Chemical compounds’ modification due to the substituents’ changing around the 1,2,4-triazole fragment fundamentally changes the type of biological activity of new molecules. This approach was chosen by the majority of scientists as promising one for the new biologically active substances’ search among the 1,2,4-triazole derivatives. The priority, relevance and perspective of such researches have been proved by not only domestic scientists’ teams. Recently, foreign investigators from Turkey, India, Korea, China, Egypt, etc. have been actively searching for new biologically active substances among the 1,2,4-triazole derivatives. The analysis of modern literary sources on the study of the new 1,2,4-triazole derivatives’ biological activity allows us to establish certain features of the various functional substituents’ influence on the types of biological activity and convincingly proves the outlook of further synthetic tests in the compounds’ specified series.

The development of effective and safe therapeutic agents using 1,2,4-triazole derivatives is gaining momentum in today’s conditions. The value of such drugs is determined by the rapid and prolonged biological action, which is not accompanied by abrupt changes in homeostasis and pronounced side effects, which are characteristic of most pharmacological drugs of synthetic origin. In the context of a limited range of domestic antimicrobial and antifungal veterinary drugs on the national pharmaceutical market, one of the directions for solving this problem is the search, study, research, and development of drugs with antimicrobial and antifungal activity. The aim of this work was to study the mutagenic effects with the prediction of carcinogenicity of 4-((5-decylthio)-4-methyl-4-H-1,2,4-triazole-3-yl)methyl)morpholine with the prospect of further creation of new dosage forms for the treatment fungal pathologies of the skin. Materials and methods. Staph was used to study the effect of 4-((5-decylthio)-4-methyl-4-H-1,2,4-triazol-3-yl)methyl)morpholine in vitro Staphylococcus aureus, strain 209, its UV-2, UV-3 mutants and primary cell cultures. Accounting for gene mutations of microorganisms in the system of metabolic activation (Ames test) was carried out according to the method of L. M. Fonshtein in accordance with the requirements of “Methodological recommendations for assessing the mutagenic properties of new medicinal products” (Kyiv, 1996), supplemented by the methodology according to the recommendations of “Preclinical research of veterinary medicinal products” (edited by I. Ya. Kotsiumbas). Results. The results of studying the activity of 4-((5-decylthio)-4-methyl-4-H-1,2,4-triazole-3-yl)methyl)morpholine on a model of culture of tumor ascetic cells showed that at concentrations of 1.4 mg/ml, 0.8 mg/ml, 0.3 mg/ml, 0.015 mg/ml it was led to the regression of tumor cells of Ehrlich’s carcinoma and C-37 sarcoma. In experiments with the Nk/L y strain, the same concentrations of 4-((5-decylthio)-4-methyl-4-H-1,2,4-triazole-3-yl)methyl)morpholine significantly slowed down cell growth. The results of the studies indicate a pronounced cytogenetic effect of thiophosfamide and sarcolysin, which suggests their metabolic activation in the body, as evidenced by a pronounced aberration of chromosomes. When comparing the cytogenetic effect of equimolar concentrations, the absence of cytogenetic activity of 4-((5-decylthio)-4-methyl-4-H-1,2,4-triazole-3-yl)methyl)morpholine was revealed. Conclusions. The positive results of studying the specific activity of 4-((5-decylthio)-4-methyl-4-Н-1,2,4-triazole-3-yl)methyl)morpholine in experiments in vitro were obtained which indicates the expediency of its extensive study in experimental animal tumors. In addition, according to these studies, no mutagenic effect was found at the doses that were used to predict carcinogenicity. Thus, it can be concluded that there is no cytogenetic effect.

1,2,4-Triazole and its derivatives are a promising class of organic compounds. For a long time, they remain in the spotlight due to a number of unique properties: high ability to chemical transformations, the presence of various types of biological activity and, of course, low toxicity. Also, a number of 1,2,4-triazole derivatives are currently well studied and implemented in various spheres of human life as effective drugs, various plant protection products (growth stimulants, fungicides, herbicides), anti-corrosion materials, plasticizers, etc. The aim of the work was to analyze and systematize new data on antimicrobial and antifungal activity of 1,2,4-triazole derivatives and to select a promising area of ​​research based on the accumulation of a large amount of information on the properties of new 1,2,4-triazole derivatives. The analysis of modern sources of information in recent years argues and proves the prospects for finding new biologically active compounds in a number of 1,2,4-triazole derivatives. The information obtained clearly indicates the possibility of using 1,2,4-triazoles, which contain a Sulfur atom, as objects of study. 1,2,4-Triazole is one of the most well-known classes of biologically active compounds, which has a wide range of biological action. Derivatives of 1,2,4-triazole are characterized by the presence of antibacterial, antifungal, hypoglycemic, antihypertensive, analgesic, anti-inflammatory, antitumor, antiviral activities. The trend of creating new effective drugs based on 1,2,4-triazole derivatives is growing. Some of the drugs are 1,2,4-triazole derivatives: ribavirin (an antiviral agent), risatriptan (a selective 5HT1 serotonin receptor agonist), alprazolam (an anxiolytic agent), fluconazole, and itraconazole (antifungal drugs). Derivatives of this compound have proven themselves well in veterinary medicine. Drugs such as Avesstim, Trifuzol, Trifuzol-neo are immunostimulants and in various dosage forms (1%, 2% solutions, suppositories) are used in veterinary farms, in the private livestock sector and for pets. These facts are the best example for understanding the prospects of finding new molecules among 1,2,4-triazole derivatives.

The aim of the work was to study the current state of domestic legislation of state regulation in the field of licensing the activities of business entities manufacturing veterinary medicinal products and its harmonization with the requirements of the European Union. Materials and methods. The research materials were regulatory and legislative acts, regulations and principles of the state policy of Ukraine connected with licensing the activities of business entities manufacturing veterinary medicinal products, in force from 2015 to the present. To carry out this study, the methods of information retrieval, systematization, analytics, graphic, comparison, and data generalization were used. Results. The article presents the main results of the analysis of the Ukrainian legislation which regulates the production of veterinary medicines and preparations. According to the results of the analysis, it was found that in the period from 2015 to 2018, Ukrainian manufacturers of veterinary medicinal products worked in such conditions that did not require a license for this type of activity. By the decree of the President of Ukraine, the program of sustainable strategic development of the country “Ukraine-2020” was approved which provided for reforms in the format of deregulation and the development of entrepreneurship and excluded the necessity of licenses for veterinary drugs production. Conclusions. Based on the study, it can be concluded that the Law of Ukraine “On Licensing of Types of Economic Activities” dated March 3, 2015 No. 222-VIII was actually aimed at reducing the governmental influence and regulatory pressure on the activities of business entities involved in the production of veterinary medicinal preparations.