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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.

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 conducting pharmaco-toxicological assessment of Gelmintal Mini Syrup based on a combination of moxidectin and toltrazuril. Materials and methods. The study was carried out on 64 white male rats and 40 white mice. Each animal species was divided into 4 equivalent groups of 6–10 animals each. When studying acute toxicity, the drug was administered in the form of a syrup (without dilution) to animals once at doses of 11 400, 22 800 and 28 500 mg/kg; when studying subchronic toxicity, the drug was administered daily for 14 days at doses of 570, 1425 and 2850 mg/kg (1/10 and 1/20 and 1/50 of the maximum possible dose administered into the stomach according to the vivisection results). When studying acute toxicity, the animals were followed up for 14 days; we recorded the general condition and behavior of the animals, changes in their body weight, the manifestation of toxic symptoms or possible death. When studying subchronic toxicity, the animals were followed up during the entire period of the drug use (14 days); on the 15th and 24th days of the experiment, we performed euthanasia, collected the blood to determine hematological and biochemical values, and carried out macroscopic examination of the organs. Results and discussion. We did not record the animals’ death at doses of 11 400, 22 800 and 28 500 mg/kg; and no signs of intoxication were noted for the entire follow-up period. LD50 of Gelmintal Mini Syrup exceeds the dose of 28500 mg/kg, i.e. the drug is classified as the 4th hazard class. The results of the studied subchronic toxicity showed that the drug was inactive at doses of 570 mg/kg, 1425 and 2850 mg/kg when administered orally for 14 days.

The purpose of the research is studying acute toxicity of supramolecular complexes of fenbendazole with different polymers obtained by mechanochemical technology as compared to the substance of the drug when administered to the stomach of white mice. Materials and methods. The acute toxicity parameters of supramolecular complexes of fenbendazole (SMCF) with different polymers were studied under the “Guide to experimental (preclinical) study of new pharmacological substances” and other rules. The drugs were administered once to the stomach of white mice of both genders with a body weight of 16–18 g at doses of 7,000, 10,000, 15,000 and 20,000 mg/kg by the drug. Each dose was tested on 10 white mice. For 14 days, we observed the general condition and behavior of animals, symptoms of intoxication and possible death. Postmortem examination was performed for the dead animals. Acute toxicity was determined by Litchfield and Wilcoxon (M. D. Belenky, 1963). Results and discussion. LD50 of the SMCF and the major drug of fenbendazole could not be established due to low toxicity. LD50 of the SMCF administered to the stomach of white mice was 20 000 mg/kg.

The purpose of the research: to study acute toxicity and anthelmintic efficacy of khimedol, a new anthelmintic preparation. Materials and methods. Khimedol, anthelmintic preparation which was received by means of streamlined synthesis in the Institute Chemistry and Chemical Technology of National Academy of Science of Kyrgyz Republic was the object of the research (KG patent No. 1954, 2017). Experiments on identification of acute toxicity of khimedol were carried on 36 clinically healthy white mice of both genders with body weight about 18-22 g by means of oral supplementation of medication in the form of 10 % hydrous solution in dose of 1,000, 1,500, 2,000, 2,500 and 3,000 mg/kg of body weight. Statistical manipulation of digital materials was carried by the probit analysis method. Testing of anthelmintic efficacy of the medication was performed by control-test method on 40 lambs, which were infested by moniezia spontaneously. Khimedol was individually given to the lambs by mouth (per os) in a form of hydrous solution as a single dose of 10, 20, 30 mg/kg of body weight. Control animals were not undergone deworming. Flotation method was used for coprological surveys. Results and discussion. Maximum tolerated dose of khimedol (LD 0) for the white mice was 1,000 mg/kg, LD 16 - 1420 mg/kg, median lethal dose (LD 50) - 2,110 (1,563÷2,845.5) mg/kg, LD 84 - 2,970 mg/kg, and absolutely lethal dose (LD 100) - 3,000 mg/kg. Therefore, khimedol is a medication with low toxic potential to animals. During the experiments on testing the anthelmintic effectiveness of khimedol on sheep with monieziasis it has been established that the preparation exhibits its anthelmintic efficacy in a dose of 10 mg/kg: among 10 lambs 8 were treated from worms, and the number of eggs in 1 g of feces was decreased by 83.43%. Administration of khimedol in a dose of 20 and 30 mg/kg leads to full recovery of an animal from monieziasis (100%).

The purpose of the research is to characterize the methods for testing and assessment of efficiency of anthelmintics against trichinellosis and hymenolepidosis in laboratory model.Materials and methods. The literature and own research results have been analyzed as regards testing and efficiency assessment of anthelmintics against trichinellosis and hymenolepidosis in white mouse as a laboratory model weighting 14–16 g that was infected experimentally with Trichinella spiralis larvae in a dose of 200 larvae per specimen and with Hymenolepis nana eggs in a dose of 200 infective eggs per specimen. The medication efficiency was considered subject to the results of a small intestine autopsy on the 2nd and 4th days after the medications were injected to treat trichinellosis and hymenolepidosis in white mice accordingly.Results and discussion. A detailed description has been given for progressive methods to test medication and new chemical compound effect on nematode activity in white mice infected experimentally with T. spiralis, and on cestode activity in white mice infected experimentally with H. nana in a dose of 200 larvae and 100–200 eggs per specimen accordingly. In order to study effectiveness, the test medications were introduced into animals on the 3rd day in the trichinellosis case and on the 13th day in the hymenolepidosis case. Anthelmintic effectiveness was taken into consideration based on helminthologic autopsy of small intestines in animals on the 2nd and 4th days after the medications were given against T. spiralis и H. nana accordingly. The helminthes found in the experimental and control (uncured) animals were counted by a checkup analysis, namely, in comparison with the control animals.

Objective of research: studying of acute toxicity of supramolecular complexes of Fenbendazole developed using chemical mechanical technology in comparison with the substance of preparation injected to the stomach of white mice and rats. Materials and methods: The research of parameters of acute toxicity of the supramolecular complexes of Fenbendazole was conducted according to «Guidelines for experimental (pre-clinical) studies of new pharmaceutical compounds», and other rules. Preparations were injected to the stomach of white rats and mice of both gender with the body mass 160–180 and 18–20 g. at a single dose 7 000, 10 000, 15 000 and 20 000 mg/ kg, respectively. Each dose was investigated on 6 white rats and 10 white mice. Within 14 days we observed the general health status and behavior of animals, symptoms of intoxication and eventual death. We also conducted postmortem examinations of the fallen animals. The parameters of acute toxicity were determined by the method of Litchfield J. and Wilcoxon F. (M.D. Belen’ky, 1963). Results and discussion: It was not possible to detect LD50 in supramolecular complex of Fenbendazole and the base drug Fenbendazole due to the low toxicity. The maximum endurable dose of supramolecular complex no. 2 was 10 000 mg/kg, LD50 -value in supramolecular complex of Fenbendazole no. 2 at injection to the stomach of white mice and rats was 20 000 mg/kg.

The treatment of experimental hymenolepiasis in larval and imaginal stages of parasite development with praziquantel in combination with indomethacin or ibuprofen and a complex of antioxidant vitamins C, E, β-Carotene is an effective way of protection of the host genome of somatic and generative cells and the full dehelmintization of the host. The most effective way of treatment of hymenolepidosis in 6–11 year-old children is the concomitant therapy with praziquantel applied at a single dose of 25 mg/kg of body weight plus ibuprofen at a rate of 20 mg/kg of body weight, and a complex of antioxidant vitamins C, E, β-Carotene with selenium (2 additional days). Praziquantel is administered to adults at the same dose in combination with indomethacin and a complex of antioxidant vitamins C, E, β-Carotene with selenium according to the same regimen. Materials and methods 175 male mice СВА at 4–5 month of age and of a weight 18–20 g served as a material for experimental study. The clinical reasoning of a concomitant therapy for hymenolepidosis has been performed at Vitebsk Regional Clinical Hospital of Infectious diseases. Two series of experiments were conducted: the 1st – on laboratory animals, the 2nd – with the involvement of patients with hymenolepidosis and blood donors. In the first series the impact of hymenolepidosis therapy with praziquantel, phenasal, albendazole, indomethacin, ibuprofen and a complex of antioxidant vitamins C, E, β-Carotene with selenium and their combinations on the results of alkaline single cell gel electrophoresis (SCGE) by N. P. Singh et al. with modification of B. Hellman et al. as well as the intensity of dwarf tapeworm infection (in imaginal stages) were studied. As a common internationally agreed standard for the estimation of genotoxic effect of environmental factors by the DNA-comet assay we used the «tail moment» which was measured by multiplying the percentage of DNA (fluorescence) in the tail by the length of tail. To estimate the cytotoxic effect, 100 cells were randomly taken for analysis and the percentage of apoptosis with a small sized nucleus and a large tail dispersed in all directions was determined. The experiments were conducted on 175 mice divided into two groups. The first group contained 75 mice and was a control group. The second series was devoted to development of the treatment model for hymenolepidosis in humans using praziquantel with indomethacin or ibuprofen and a complex of antioxidant vitamins C, E, β-Carotene with selenium. The clinical experiments were conducted on 16 patients with hymenolepidosis, 10 of which (first group) were at the age of 6 to 11 years (6 boys and 4 girls) and 6 patients (second group) – at the age of 25 to 36 years (4 men and 2 women). Results and discussion The effect of concomitant therapy (praziquantel, phenasal, albendazole), antioxidant therapy (vitamins C, E, β-Carotene with selenium) on the genome of a host as well as the intensity of hymenolepidosis infection in mice infested by the eggs of dwarf tapeworms in imaginal stages at a dose of 20 eggs/g body weight ( from 11 to 13 days) were studied. The administration of all drugs and their combinations to the animals of control groups did not lead to a significant increase in tail moment of bone marrow cells and apoptotic cells in comparison with the data of intact control except the administration of phenasal.

Objective of research: to study the caryopathic effect of bio-preparation Bacillus subtilis 12В on the status of spermatogenic epithelium of white mice after a single intra-abdominal administration of the Fasciola hepatica extract. Materials and methods: The investigations were conducted on white male mice after oral use of preparation Sporovite based on B. subtilis 12B; then the intra-abdominal injection of F. hepatica extracts at a dose of 100 mkg/head was applied. The protein extract from F. hepatica was administered to mice of the second group, and animals of the third group received only the probiotic Sporovite. Animals of the fourth group did not get the preparation and served as controls. 48 hours later the animals were killed; touch smears obtained from testis were stained by the Romanovsky method and examined under a microscope what enables to determine the mitotic index and the number of pathological meiosis forms. The experiments were conducted on lambs whose seminal vesicles were placed into a solution of 10% Formalin and examined histologically. 2-3µ-thick slices were stained with Haematoxylin and Eosin by Van Gieson method and examined under a microscope at 50, 400 and 1000 x magnifications. Results and discussion: During the pathomorphological and caryomitotic studies of testis of white mice and lambs after administration of Sporovite on the background of intra-abdominal injection of F. hepatica extract the reduction of negative effects on the status of spermatogenic epithelium of testis in animals wasn’t observed. A decrease in mitotic index by 2-3 times and a high amount of pathological forms were registered. The number of metaphases with preterm chromosome disjunction under the joint effect of F. hepatica and B. subtilis extracts has decreased by half.

Acute toxicity of Ricazol based on Ricobendazole by oral administration and intramuscular injection in white outbread mice and rats as well as by dermal ad-ministration in white rats is studied. To test the parameters of acute oral toxicity of Ricazol the compound was administered singly to experimental animals (at various doses). General well-being and behavior of animals, manifestation of intoxication symptoms and possible death of animals were observed within 14 days. Post-mortem examination of dead animals was carried out. To investigate acute skin toxicity of Ricazol the compound was given singly to experimental animals on the skin area (size 5cm × 5cm) at the doses of 10000, 15000 и 20000 mg/kg of active ingredient. LD50 value by injection into the stomach for mice was 10000 mg/kg, for male rats – 2500, female rats – 2700 mg/kg. LD50 by dermal administration in rats was 11200 mg/kg, by intramuscular injection in rats – 2500, in male mice – 4900 mg/kg.