Background. Integrated plant protection against diseases, pests and weeds is the most important element of agricultural technology. The use of fungicides is important not only to increase plant yields, but also to obtain high-quality crops. Most chemical plant protection products (CPPP) include molecules of organic compounds as active ingredients (AI), which are poorly soluble in water, which requires the development of formulations for them that allow for the uniform application of AI to plants and effectively protect them from diseases and pests. Materials and methods. To solve the problems of resistance, it is proposed to develop multi-component and polyfunctional seed dressings for grain crops using mechanochemical methods. The compositions obtained using this technology in the form of solid dispersions had increased solubility and a wide range of biological activity. The objects of study were triazole derivatives - tebuconazole and propiconazole, polysaccharide arabinogalactan and plant growth regulators. Results. The experimental compositions obtained in the work had a strong retardant effect on sprouts of soft spring wheat of the Novosibirskaya 31 variety. The addition of the known growth stimulator floroxan and a biostimulant in the form of silica did not help to remove this retardant effect, although the softening effect of floroxan was previously shown when using compositions based on tebuconazole. Conclusion. The use of mechanochemical modification methods for a number of triazole derivatives made it possible to obtain compositions that significantly inhibited root formation and shortened sprouts, caused abnormal germination of grains, which ultimately affected germination, as well as the accumulation of biomass in sprouts and seedlings. The obtained results confirm the prospects for the development of multicomponent drugs using mechanochemical methods to solve the problems of resistance, solubility and expansion of biological activity. EDN: HDOBXE

Background. The zooparasitic complex of sheep in the Altai Mountains is characterized by diversity and is represented by almost all the main classes of pathogens of invasive diseases – nematodes, trematodes, cestodes and parasitic arthropods. Purpose. To develop and characterize the parasiticidal activity of a new complex therapeutic agent with a broad spectrum of action, allowing for minimization of the volume and frequency of drug use. Materials and methods. Using the methods of mechanochemical modification of fenbendazole (FBZ) and ivermectin (IVM) substances with the help of licorice extract (LE), compositions in the form of solid dispersions with increased solubility were prepared. The compositions were studied against helminths of the gastrointestinal tract on spontaneously infested sheep. Experimental and control groups of animals were formed, consisting of 7-20 heads. Feeding was carried out with samples of compositions with different doses of substances. Results. Parasitic activity was characterized by ovoscopic examinations of fecal samples of experimental and control animals. It was established that the parasitic agent in the form of a solid dispersion obtained from fenbendazole and ivermectin with licorice extract, in a dose of FBZ (3 mg / kg of animal weight), IVM (0.2 mg / kg of animal weight) showed 100% effectiveness in strongylosis of the gastrointestinal tract and respiratory system, as well as in monieziasis and dicrocoeliasis of sheep. The insecticidal effectiveness of the drug in melofagosis was 89.5%. Conclusion. By means of mechanochemical modification of the substances of FBZ and IVM in the presence of licorice extract, a complex therapeutic drug was obtained that has increased solubility and a wide spectrum of parasiticidal activity, allowing to minimize the volume and frequency of drug application. EDN: TSSNMC

Background. The development of new forms of anthelminthic drugs, such as supramolecular complexes of fenbendazole, is a topical task in the conditions of increasing parasite resistance to traditional drugs. Improvement of the solubility and bioavailability of fenbendazole is possible by mechanochemical modification of the substance with polymeric substances. Purpose. Synthesis and comparative evaluation of acute toxicity of new supramolecular forms of fenbendazole in an experiment on white mice. Materials and methods. The technology of mechanochemical modification of fenbendazole substance (FBZ) with the help of polymeric substances - PVP, arabinoga-lactan (AG), liquorice extract (LE) - produced solid dispersions with increased solubility. The acute toxicity of the supramolecular complexes FBZ:PVP: LE (10:45:45) and FBZ:PVP:AG (10:45:45) was studied in white mice. LD50 values were determined using probit analysis methods. Clinical observations and necropsy were used to assess toxicity. Statistical processing of the data was performed using AtteStat. Results. New supramolecular forms with higher acute toxicity than pure fenbendazole were obtained by mechanochemical processing of fenbendazole in the presence of polymeric substances. The LD50 for FBZ:PVP: LE was 43729.97 mg/kg and for FBZ:PVP:AG - 49997.07 mg/kg. The FBZ:PVP: LE complex was characterised by more pronounced dose-dependent effects, including loss of appetite, body weight and neurological symptoms compared to FBZ:PVP:AG. The highest mortality was observed in the group receiving FBZ:PVP: LE at a dose of 20000 mg/kg (50%). Conclusion. The obtained data indicate the promising use of supramolecular forms of fenbendazole to improve anthelminthic efficacy. However, increased toxicity requires further safety studies and dose optimization studies. EDN: LEOJRO

Background: Due to the fact that animal parasitic diseases often occur in the form of mixed infections, it is necessary to use complex drugs with a combination of active substances that act against different classes of helminths. Fenbendazole has a wide spectrum of nematocidal action and is less effective against cestodes. Considering that sheep are often infected with both gastro-intestinal nematodes and cestodes, a complex drug based on fenbendazole, niclosamide with polyvinylpyrrolidone polymer, was developed using mechanochemical technology in order to increase its solubility and bioavailability and reduce the dosages and side effects. Objective: This study aimed to evaluate the influence of mechanochemical technology on the efficacy of complex solid dispersions of anthelmintics against cestodoses and nematodoses. Methods: The influence of different types of mills (roller and planetary mills), levels of energy intensity (20, 40, 60 g), and component ratio (2:20:78; 3:30:67; 4:40:56) during mechanochemical processing was studied on the anthelmintic efficacy of complex solid dispersions of fenbendazole, niclosamide, and polyvinylpyrrolidone in laboratory models of trichinellosis and hymenolepiosis of white mice, and on sheep naturally infected with helminths. Results: The efficacy of complex solid dispersions obtained in the planetary mill was higher than the activity of dispersions obtained in a roller mill. It showed 87.5, 96.36, 83.77, and 99.39% efficacy, respectively, against experimental trichinellosis, hymenolepiosis of white mice, gastrointestinal nematode infection and monieziosis of sheep at a ratio of 2:20:78. The basic drug – fenbendazole demonstrated 31.37 and 22.77% activity against experimental trichinellosis and gastro-intestinal nematode infection of sheep. The basic drug, niclosamide, showed 36.37% efficacy against hymenolepiosis in mice and 28.31% against monieziosis in sheep. It was established that with an increase in the energy intensity level of the planetary mill (20, 40, and 60 g), the decrease in the efficacy of solid dispersion occurred from 73.90 to 59.12% against T. spiralis and from 92.73% to 79.81% against H. nana. Conclusion: The use of mechanochemical technology for the production of solid dispersions of fenbendazole and niclosamide with polyvinylpyrrolidone makes it possible to increase the anthelmintic efficacy by 2.7–3 times compared to the activity of basic substances. It was noted that the complex solid dispersions of anthelmintics obtained in a planetary mill had 7.51–10.17% greater activity in comparison with the samples obtained in a roller mill. The most optimal ratio of active substances was 2:20:78 at a 20 g level of energy intensity of the planetary mill.

The importance of the role of a formulation in realizing the potential of a new substance and promoting the preparation (medicinal or pesticide) on the market is undeniable. When developing a pesticide formulation, it is necessary to address the following issues: a convenient application form, drug fixation on the plant surface, penetration of an active substance into the plant, and high efficiency against weeds, plant diseases and pests. The modern formulations of nanoscale pesticides facilitate better realization of the biological potential of an active substance. This article gives a brief overview of the literature on pesticide formulations and their varieties, the preparation methods and effectiveness published in the last 10 years, with a particular focus on the authors' own work.

The research purpose was to study the dialysis of triclabendazole (TCB) and its solid dispersions (SDs) obtained by mechanochemical methods by modifying TCB with polyvinylpyrrolidone (PVP), arabinogalactan (AG) and succinic acid (SA). Solid dispersions of the following compositions were obtained: TCB:AG:PVP (1:4,5:4,5), TCB:SA:AG (1:1:8) and TCB:SA:PVP (1:1:8), which were characterized by their solubility in water. To study the TCB release from the obtained SDs (dialysis), we used a laboratory installation consisting of a thermostated glass with a buffered solution (sodium borate) with pH 9.18 (intestinal environment). The TCB substance concentration in the dialysate was determined by HPLC the data of which determined that the TCB release into the buffered solution at different rates depended on the SD composition. It was found that SA included in the SD composition significantly increased the TCB release rate, apparently due to the buildup of a salt form from TCB (weak base) and SA (weak acid). The following conclusions were drawn: the increase in the TCB solubility in the studied SDs, as well as the increase in the rate of the TCB release from the SDs with succinic acid was consistent with previously obtained data on high antiparasitic activity of these SDs in sheep fascioliasis.

Helminth infections pose a significant economic threat to livestock production, causing productivity declines and, in severe cases, mortality. Conventional anthelmintics, exemplified by fenbendazole, face challenges related to low solubility and the necessity for high doses. This study explores the potential of supramolecular complexes, created through mechanochemical modifications, to address these limitations. The study focuses on two key anthelmintics, praziquantel (PZQ) and fenbendazole (FBZ), employing mechanochemical techniques to enhance their solubility and efficacy. Solid dispersions (SD) of PZQ with polymers and dioctyl sulfosuccine sodium (DSS) and fenbendazole with licorice extract (ES) and DSS were prepared. The helminthicidal activity of these complexes was assessed through helminthological dissections of sheep infected with Schistosoma turkestanicum, moniesiasis, and parabronemosis. In the assessment of supramolecular complex of FBZ (SMCF) at doses ranging from 1.0 to 3.0 mg/kg for the active substance (AS), optimal efficacy was observed with the fenbendazole formulation containing arabinogalactan and polyvinylpyrrolidone at a 3.0 mg/kg dosage. At this concentration, the formulation demonstrated a remarkable 100% efficacy in treating spontaneous monieziosis in sheep, caused by Moniezia expansa (Rudolphi, 1810) and M. benedenii (Moniez, 1879). Furthermore, the SMCF, administered at doses of 1.0, 2.0, and 3.0 mg/kg, exhibited efficacy rates of 42.8%, 85.7%, and 100%, respectively, against the causative agent of parabronemosis (Parabronema skrjabini Rassowska, 1924). Mechanochemical modifications, yielding supramolecular complexes of PZQ and FBZ, present a breakthrough in anthelmintic development. These complexes address solubility issues and significantly reduce required doses, offering a practical solution for combating helminth infections in livestock. The study underscores the potential of supramolecular formulations for revolutionizing helminthiasis management, thereby enhancing the overall health and productivity of livestock.

Objective:This study aimed to examine the efficiency of newly formulated drugs based on mechanochemical modification of two widely used anthelmintic substances in suspension formulations against the main classes of helminths and parasitic arthropods. Materials and Methods:Solid-phase co-grinding of two substances, i.e., ivermectin (IM) and niclosamide (NS), with licorice extract and sodium succinate was performed in liquid-phase processing to obtain suspension formulations. Drug preparations were administered to the sheep of the experimental groups (5 experimental groups of 8 heads) with different concentrations of active substances, i.e., 3.0, 5.0, and 10.0 mg/kg of body weight (BW) NS and 0.2-mg/kg BW IM. Aqueous suspensions of the original substances in dosages of 0.2-mg/kg BW IM, 10.0-mg/kg NS, and placebo were included as controls. Efficacy of the formulations against gastrointestinal strongyles, Trichuris spp., Moniezia spp., and nasal bot larvae (Oestrus ovis) was assessed in naturally infected sheep by the number of surviving adult parasites post-treatment in the gastrointestinal tract, nasal passages, and sinuses. Results:Formulated suspensions showed an increased solubility of 5.5-13.1 times compared to the original substances. Treatment of sheep with the SusIN-10 drug containing 0.2-mg/kg BW IM and 10.0-mg/kg NS showed 100% efficiency against gastrointestinal strongyles, Moniezia, and nasal bot larvae. Formulations containing 0.2-mg/kg BW IM and 3.0- and 0.5-mg/kg NS could eliminate all of the Trichuris worms. Administration of original substances of IM and NS with recommended dosages did not result in the adult parasites' complete elimination. Conclusion:Modification of the anthelmintic substances through mechanochemical methods made it possible to create formulations with a targeted spectrum of action, significantly higher water solubility, and optimal parasiticidal activity.

The purpose of the research is to study the anthelmintic efficacy of suspensions based on a combined solid dispersion of Fenbendazole and Niclosamide.Materials and methods. Mechanochemistry methods were used to prepare suspensions of Fenbendazole (FBZ) and Niclosamide (NSM) substances, in particular, liquid phase grinding of substances with additives (licorice extract, polyvinylpyrrolidone (PVP)) in water or in aqueous sodium carboxymethylcellulose (NaCMC) solution. The grinding was conducted in LE-101 roller mill at energy intensity of 1 g for 1 hour at a roll rotation speed of 60–70 rpm. The resulting suspension samples of combined FBZ and NSM dispersions were studied for cestodocidal activity on a laboratory model of hymenolepiosis of white mice that were infected at a dose of 200 infective Hymenolepis nana eggs per animal.Results and discussion. The 100% efficacy of a combined NaCMC-based drug suspension containing FBZ 13 mg and NSM 130 mg in 1 g of suspension was achieved at a dose of 20 mg/kg of NSM and 2 mg/kg of FBZ. The suspension based on licorice extract, NaCMC, and dioctyl sulfosuccinate sodium salt containing FBZ 18.6 mg and NSM 186 mg in 1 g of suspension at the same dose, i.e. 20 mg/kg of NSM and 2 mg/kg of FBZ showed 71.43% efficacy against H. nana. The suspension based on licorice extract and NaCMC containing FBZ 24.6 mg and NSM 246 mg in 1 g of suspension at the same dose showed a 62.0% effect against H. nana. The activity of the basic drug, the FBZ and NSM suspension was 28.58% at this dose without using mechano-chemical treatment.

The purpose of the research is to analyze the dynamics of fenbendazole (FBZ) and niclozamide (NZM) release from their solid dispersions (SD) of various compositions by dialysis through various semipermeable membranes in model systems that correspond to stomach and intestine environments. To evaluate the parasitocidal activity of experimental mixture compositions.Materials and methods. The study used substances of FBZ and NZM, and the polymer, polyvinylpyrrolidone (PVP). Mechanical processes were carried out in a LE-101 roller mill and an AGO-2 orbital centrifugal mill at different power density levels. The resulting SD of various compositions were studied for solubility. The dynamics of FBZ and NZM substance release from the SD were studied in a laboratory setup consisting of a temperature controlled glass with buffer solutions with pH = 9.18 (intestinal environment) and pH = 1.0 (stomach environment). The substance concentration in the dialysate was determined by HPLC and UV spectroscopy. The resulting complex SD of FBZ and NZM were studied for cestodocidal activity in a laboratory model of hymenolepiosis of white mice.Results and discussion. It was found that the substances release into a buffer solution with pH = 9.18 from the SD obtained in the roller mill is higher than that of the SD obtained in the AGO activator. The dialysis of the experimental compounds in a model system with a gastric juice medium observed only FBZ substance penetration through the membrane, which can be explained by protonation of the FBZ molecule which is a weak base. The NZM molecule, being a neutral molecule, does not penetrate through the semi-permeable partition into the hydrochloric acid environment; it remains entirely inside the dialysis bag. High anthelmintic efficacy rates (up to 100%) of SD complex FBZ : NZM : PVP obtained in the AGO activator and in the roller mill were recorded for the SD of composition 2 : 20 : 78 in the mice with hymenolepiosis. The activity of the base drug, the niclozamide substance, was 27.69%, which is 3 times lower than the activity of the resulting complex dispersions.

ВЫСВОБОЖДЕНИЕ СУБСТАНЦИЙ ФЕНБЕНДАЗОЛА И ФЕНАСАЛА ИЗ ИХ ТВЕРДЫХ ДИСПЕРСИЙ

The purpose of the research is to obtain and test a complex drug Aniverm-2.0% based on the ivermectin substance by free feeding in a mixture with concentrated feed against parasitosis of cattle, sheep, and horses.Materials and methods. Aniverm-2.0% obtained by mechanochemical technology was tested on a farm in the Shatoy Region, the Chechen Republic, on 900 sheep, 180 cattle and 156 horses in March-April 2023. To determine the infection rate, coproovoscopic examinations were conducted on 80 samples from sheep, 20 samples from young cattle and 30 samples from horses using the Fulleborn’s flotation method with a saturated sodium chloride solution. Sheep were dewormed using a group method. The drug was mixed with feed per 0.3 mg/kg for the AS or 60 mg for the drug per animal. The young cattle were kept by tie-up housing and therefore they were given Aniverm-2.0% once at a dose of 0.2 mg/kg for the AS individually in a mixture with feed. The horses were given the drug in a group method at a dose of 0.2 mg/kg for the AS or 1.5 mg/kg for the drug. Fecal samples from all animals were examined before and 2 weeks after the drug.Results and discussion. A 100% rate of infection of the sheep by gastrointestinal nematodes (Strongylata, Nematodirus spp., Trichocephalus spp.) was determined with an average number of eggs 633.3 in 1 g of feces. In 20 fecal samples from the young cattle, 16 were found to have Strongylata eggs (prevalence = 80.0%) with 222.2–280.5 specimens of Strongylata eggs found in 1 g of feces. Strongylata eggs were found in all 30 examined fecal samples from the horses, on average, 253.3 specimens/g of feces (100%). At 2 weeks after treatment, nematode eggs were found in three out of 80 examined fecal samples from the sheep, which can be explained that the sheep did not eat the appropriate dose of the drug. The drug efficacy was determined to be 99.7%. One hundred percent efficacy of the drug was obtained on young cattle and horses.

In 2022, under the conditions of the growing experience of the IHR of the Academy of Sciences of the Republic of Uzbekistan on plants Astragalus babatagi and Astragalus xanthomeloides, optimal sowing dates and options for seed treatment with plant growth regulators and organo-mineral fertilizer were studied. The positive effect of pre-sowing seed treatment was revealed, which significantly affected the increase in seed productivity and plant phytomass. It was found that pre-sowing treatment of Astragalus babatagi seeds with Uchkun plus, Floroxan and potassium Humate Prompter preparations contributed to an increase in seed yield from one bed by 1.0, 0.98 and 0.8 g relative to scarified seeds and an increase in phytomass yield by 189, 197 and 186 g, respectively. The increase in the yield of Astragalus xanthomeloides seeds from one bed in experimental versions using Uchkun plus, Floroxan and potassium Humate Prompter increased by 0.92, 1.05 and 0.62 g, respectively, compared with the “scarification” option, and compared with the control by 1.82, 1.95 and 1.52 g, respectively. The yield of phytomass increased by 53.7, 61.2 and 30.7 g relative to the variant of scarified seeds, whereas in relation to the control these indicators increased by 103, 110 and 79.8 g, respectively.

Fenbendazole (FBZ) is one of the most widely used drugs in veterinary medicine. Modification of its physicochemical properties, in particular the parameter of solubility, contributes to a change in its biological activity, which is shown on the model of trichinellosis of white mice. An analysis of methods of obtaining new preparations of fenbendazole is presented: solid dispersions of fenbendazole with polymers, as well as combinations with polymers and succinic acid (SA) and mixed crystals of FBZ with SA. The concentration of the active substance, the stability, and the effect on biological activity were studied.

Among the most common and dangerous parasitic diseases of animals and humans is fascioliasis. The most effective against Fasciola is triclabendazole ("Fasinex 5.0%" suspension), imported by Siba-Geigi, which is practically not used in Russia due to its high cost. Considering the huge economic damage caused by fascioliasis, we have developed a new complex preparation using innovative mechanochemical technology based on the substance of triclabendazole "Triclafascid", which is 5 times more active than the substance of triclabendazole against fascioliasis. The drug is an intermolecular complex in the form of an easily flowing solid dispersed powder with a size of 0.1–10 microns. The drug is administered orally once to cattle and sheep for therapeutic and prophylactic purposes for acute and chronic fascioliasis, to sheep at a therapeutic dose of 2.0 mg/kg and to cattle 2.5 mg/kg for the AI, respectively, and 20 and 25 mg /kg for the drug, once individually in the form of an aqueous solution. In case of mass deworming of animals, it is convenient to give the anthelmintic by a group method to 10–20 animals, mixed with mixed feed at a dose of 3.0 mg/kg for the AI (for the preparation 30 mg/kg).

The substance fenbendazole is included in the composition of many anthelmintic drugs, in which the “chemical stability” parameter is one of the main characteristics when obtaining permission for the use of drugs in veterinary practice. Fenbendazole is characterized by low solubility in water and therefore the content of the substance is overestimated in its preparations, which increases the cost of the drug as well as the safety risks of pharmacotherapy. The possibilities of mechanochemical modification of fenbendazole were evaluated in order to improve the solubility index. During the mechanical processing treatment of the substance in the presence of polymeric substances, solid dispersions are formed, which have increased solubility and high anthelmintic activity. The inclusion in these dispersions of the third component, which is succinic acid, did not significantly change the solubility of fenbendazole. In all these dispersions, the substance remained unchanged both during the preparation of its solid dispersions and during their storage. When fenbendazole is modified in an organic solvent medium, the substance is partially converted into oxfendazole, which is one of its metabolites. The chemical stability of fenbendazole was confirmed via HPLC/MS and NMR spectroscopy. The anthelmintic activity of these compositions was evaluated and it was found that they have a high nematicidal activity.

The purpose of the research is to study the influence of various technological factors on obtaining of complex solid dispersions of anthelmintics with polyvinylpyrrolidone and licorice extract on anthelmintic efficacy in experimental trichinellosis of white mice.Materials and methods. The study of the nematodocidal activity of complex solid dispersions samples based on fenbendazole (FBZ), fenasal (FNS) and praziquantel (PZQ) with polyvinylpyrrolidone (PVP) and licorice extract (LE) obtained by mechanochemical technology at different ratios of components and different exposure times was carried out on 130 white mice experimentally infected with Trichinella spiralis in two experiments. On the 3rd day after infection, the animals were divided into experimental groups of 10 animals each. Samples of various complex solid dispersions of anthelmintics were administered intragastrically to the mice of the experimental groups at a dose of 2 mg/kg according to the active substance. FBZ substance was used as the basic drug at a dose of 2 mg/kg according to the active substance. Animals of the control groups did not receive the drugs. The animals were killed by decapitation on the 4th day after experimental drug samples administration, and the activity of the drugs was counted according to the results of helminthological necropsy of the intestine, the efficacy was calculated by the type of control test.Results and discussion. The efficacy of complex solid dispersions of FBZ and FNS with PVP polymer was higher in comparison with the activity of complexes with LE at the same duration of mechanochemical treatment in a roller mill. The FBZ activity decreased from 67.05 to 37.77% with a decrease in the duration of mechanochemical treatment from 24 h to 5 h and the efficacy of the FBZ : FNS complex with LE turned out to be almost at the level of the basic drug when treated for 1 h. The use of mechanochemical technology for obtaining of a solid dispersion of FBZ : FNS with PVP for targeted delivery makes it possible to increase the anthelmintic efficacy by 2.7 times compared with the activity of the FBZ substance, and with LE by 2.2 times. It was noted that complex solid dispersions of PBZ with PZQ have lower biological activity in comparison with compositions of FBZ with FNS.

The purpose of the research is to test the efficacy of triclafascid and two solid dispersion complex preparations based on the triclabendazole substance against fasciolosis in cattle and sheep. Materials and methods. Complex preparations of triclabendazole (TCB) formulations: Succinic Acid (SA): Polyvinylpyrrolidone (PVP) (1: 1 : 8) and TCB: SA: Arabinogalactan (AG) (1: 1 : 8) were obtained by combined solid-stategrinding of the components in a fiber drum on an LE-101 ball mill at a roll rotation speed of 60 rpm with a process module of 1: 17 for 1 to 6 hours with sampling for analysis (HPLC) for changes in the TCB solubility. A comparative test of the efficacy of triclafascid and new solid dispersions (SD) of TCB complexes with SA against fascioliasis of sheep and cattle was conducted in the North-Eastern Federal District of the Caucasus in March-April 2023. To determine the Fasciola infection rate in animals, fecal samples were individually taken and examined by the Fülleborn methods using saturated aqueous NaCL solution and sequential washing. The drug efficacy was recorded at 25-30 days after deworming in analogy with "critical test". The results were statistically processed by the Student-Fisher method using Microsoft Excel 2007. Results and discussion. The resulting TCB and SA complexes with polymers had an increased solubility (up to 59–70 times) that depended on the polymer nature. The efficacy of new TCB dosage forms against fascioliasis in sheep at a dose of 1.5 mg/kg, i.e. 0.5 mg/kg less than the therapeutic dose as compared with oral triclafascid was 90.0 and 100%, respectively, and 85.7% in cattle at a dose of 2.0 mg/kg for the active substance.

The niclosamide substance (NCS) is a part of many anthelmintic and anticancer drugs. However, it has a serious drawback—the low solubility in water and physiologically active media, which leads to the high dosage required to achieve a therapeutic effect, increased cost, and enhanced toxicity. To improve the solubility of NCS, its mechanochemical modification with polymers has been suggested. This allows for increasing the solubility of NCS in 40–52 times. Such an increase in this parameter is shown not to affect the cytotoxic activity adequately. The observed selectivity towards different cancer cell cultures is discussed.

Целью исследования являются поиск и разработка методами механохимии препаратов на основе празиквантела (ПЗК) и изучение их эффективности при лечении шистосомоза овец в Республике Узбекистан.Для повышения растворимости субстанции ПЗК в воде применили метод его механохимической модификации с помощью полимерных веществ (ПВП, полисахарид арабиногалактан, сапонин в виде экстракта солодки).Суть метода заключалась в совместной твердофазной обработке исходных компонентов в металлическом барабане шаровой мельницы с регулируемой энергонапряженностью. Метод является одностадийным, экологически безопасным, исключает использование растворителей, процессов нагревания и образование отходов.Полученные при этом твердые дисперсии (ТД) представляли собой тонкие порошки с повышенной до 15 раз растворимостью, которую контролировали методом ВЭЖХ после растворения образцов ТД в воде с фиксированием концентрации ПЗК в водном фильтрате при 360 нм.Образцы ТД после растворения в воде испытывали на молодняке овец каракульской породы в частном животноводческом хозяйстве Республики Узбекистан.Результаты испытаний подтвердили высокую эффективность предлагаемых препаратов при шистосомозе овец, а именно установлена 100%-ная эффективность всех разработанных твердых дисперсий празиквантела против Schistosoma turkestanicum в дозах 2,0 и 3,0 мг/ кг массы животного.Успешная апробация разработанных композиций с заниженными в 10 раз дозами позволяет рекомендовать их к широкому использованию в ветеринарной и медицинской практике по борьбе и профилактике шистосомозов животных