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.
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.
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.
COVID-19 is a life-threatening disease that can be asymptomatic in the form of a common ARVI, or in extremely severe forms, with serious long-term consequences. Vaccination against COVID-19 is critically important to restrain the pandemic. The purpose of the study was to analyze and systematize the data of pharmacological supervision of the use of vaccines against COVID-19. For this, methods of analysis, systematization and generalization of information were used using the databases of the State Expert Center of the Ministry of Health of Ukraine, Food and Drug Administration, World Health Organisation in the period from February 24, 2021 to October 31, 2021. Currently, such vaccines are registered and approved for use in Ukraine as AstraZeneca (Covishield, SKBio), Comirnaty / Pfizer-BioNTech, Moderna, CoronaVac / Sinovac Biotech. According to official data, the effectiveness of all these vaccines is quite high. They are especially effective in preventing severe course of disease, hospitalization, and death. Sometimes the vaccination process can be with the development of a number of side effects. Responsibility for the risks associated with the production and use of vaccines dictates the need for constant monitoring of these side effects. That is why we analyzed the data of the State Expert Center of the Ministry of Health of Ukraine about adverse events after immunization from COVID-19 in Ukraine. Thus, the analysis of adverse events reported showed that they took place in 0.018% cases of the total number of vaccine doses that were administered. In the context, for each vaccine separately, the number of adverse events reported were: Covishield – 1128 cases (0.23%), CoronaVac – 419 (0.008%), Comirnaty – 854 (0.02%), AstraZeneca – 540 (0.02%), Moderna – 393 (0.02%), respectively. It should be noted that most of the reported cases of adverse events reported in Ukraine during vaccination against COVID-19 are mild predictable reactions (88.72 – 93.38%). This result allows us to speak of a fairly high predictability of the adverse events reported after COVID-19 vaccination. This is confirmed by the data of world literature. After analyzing the presented data of the State Expert Center of the Ministry of Health of Ukraine, we found that the most of adverse events reported after COVID-19 vaccination are so-called general disorders and disorders at the injection site (fever, fatigue, chills, redness, pain and swelling at the injection site). Neurological disorders ranked second in terms of the number of adverse events reported, and musculoskeletal disorders ranked third. Adverse events reported manifestations from other organs and systems had isolated cases. After using all of the above vaccines, the percentage of adverse events reported was significantly higher in women than in men, which coincides with the data of the world literature. Conclusion. Thus, the analysis of the safety of vaccines against COVID-19, registered and authorized for use in Ukraine, shows that the risks of adverse events reported after COVID-19 vaccination are rare; the most of them are mild and predictable. At the same time, these manifestations of adverse events reported cannot be compared with the health and life risks associated with the COVID-19 disease itself. Ensuring continuous monitoring of the safety of vaccine use and identifying potential side effects will further reduce and manage the risks associated with vaccine use
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