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The purpose of the research is to determine main toxicological parameters in repeated intragastric administration of Altric-Extra for veterinary use to laboratory outbred rats.Materials and methods. White outbred rats were used as a test system in the study. The experiment used clinical, toxicological, biochemical and morphological research methods.Results and discussion. Altric-Extra doses of 325 and 650 mg/kg were toxic for the laboratory animals. When administered daily intragastrically to the rats in the above doses, the drug had a negative effect on the functional status of the hemopoietic organs, and excretory and digestive systems. The main target organ for this drug is the thymus. Functional disorders in the above organs and systems are irreversible as evidenced by the post-mortem examination, general blood analysis, and biochemical blood test obtained 10 days after the drug administration was completed.

The purpose of the research is a commission test of the effectiveness of the supramolecular complex based on triclabendazole and albendazole (SMCTA) against gastrointestinal nematodes and fascioles of sheep in a previously calculated therapeutic dose.Materials and methods. The SMCTA effectiveness was tested in the North Caucasus Federal District in July 2019 on Tushin sheep spontaneously infected with gastrointestinal nematodes and fascioles simultaneously. The sheep were owned by an independent entrepreneur. Coproovoscopic examinations were carried out according to the GOST by the Fulleborn’s method using ammonium nitrate at the Republican Veterinary Laboratory of Grozny. Helminthological dissection of 5 control sheep was done to determine the intensity of infection with fascioles and gastrointestinal nematodes, and 3 sheep from each group were dissected at 14 days after dehelminthization to record the effectiveness of the drug. 4 more sheep from each group were dissected on the 25th day. The drug effectiveness was recorded by the critical test method according to the Guidelines approved by the World Association for the Advancement of Veterinary Parasitology (1995).Results and discussion. When conducting clinical trials on sheep spontaneously infected with strongylates of the gastrointestinal tract and lungs, and fascioles, a therapeutic dose was calculated when the drug was administered individually in the form of a suspension of 4.0 mg/kg for the Active Substance (2.0 for ABZ : 2.0 for TCB), 40 mg/kg for the drug, and in a mixture with concentrated feed using the group method of 5.0 mg/kg for the AS (2.5 mg/kg for ABZ : 2.5 mg/kg for TCB), 50 mg/kg for the drug. The commission test of SMCTA at a dose of 5.0 mg/kg for the AS (50 mg/kg for the drug) by the group method in a mixture with combined feed at fasciolosis and strongylatosis of the gastrointestinal tract of sheep showed, according to the coproovoscopy and helminthological dissection of animals, that 100 % efficiency was obtained. A mixture of the drug with combined feed was readily eaten by the sheep; and no side effects were noted after dehelminthization. The Commission noted the absence of side effects, high efficiency and a wide spectrum of the SMKTA effect at a 4-fold reduced therapeutic dose of 5.0 mg/kg as compared with the albendazole (7.5 mg/kg) and triclabendazole (10 mg/kg) substances.

The purpose of the research is to test the effectiveness of the supramolecular complex of albendazole and triclabendazole (Altric-Extra) in case of fasciolosis and nematodoses of the digestive tract of sheep under production conditions.Materials and methods. The test of the effectiveness of Altrik-Extra was carried out in the North Caucasus Federal District of the Chechen Republic in July 2019 on 205 sheep of the Tushino breed, spontaneously infected by gastrointestinal nematodes and Fasciola sp. Sheep infection with helminths was established by fecal examination by Fülleborn using ammonium nitrate. The average number of helminth eggs in 1 g of feces was determined using a VIGIS camera. Altric-Extra was given at a dose of 5 mg/ kg of AS (2.5 mg of albendazole and triclabendazole respectively) or 50 mg/kg in the preparation in a mixture with mixed feed by the group method. The effectiveness of the drug was determined by the results of fecal studies 14 and 25 days after deworming. After giving the drugs for three days, the clinical condition of the experimental sheep was monitored. Altric-Extra effectiveness was evaluated using the “critical test” method according to the Guidelines approved by the World Association for the Progress of Veterinary Parasitology (1995).Results and discussion. The Altric-Extra supramolecular complex in a therapeutic dose of 5.0 mg/kg of AS (for the preparation of 50 mg/kg) was 100% effective against gastrointestinal nematodes and Fasciola sp. of sheep. The sheep ate a mixture of the preparation with mixed feed; it is convenient to set in a group method; side effects after deworming is not observed.

The purpose of the research is to evaluate the acute toxicity of Altric-Extra when introduced into the stomach to mice and rats.Materials and methods. The studies were conducted in the vivarium of the All-Russian Research Institute of Fundamental and Applied Parasitology of Animals and Plants. The acute toxicity of Altric-Extra was determined on 20 white outbred male mice weighing 19.3–23.3 g, 10 animals in a group and on 30 white outbred male rats weighing 150–196 g, 6 animals in a group. Altric-Extra was administered to mice of the experimental group once into the stomach in the form of a suspension in a dose of 5,986 mg/kg at the rate of 0.2 ml/10 g of body weight. Altric-Extra rats were also administered once into the stomach in the form of a suspension at the rate of 2.0 ml/100 g body weight. As a carrier in the preparation of the suspension, 1% starch gel was used. The experimental rats of groups 1, 2, 3 and 4 were given Altric-Extra at doses of 4,580.2 mg/kg, 3,846.2; 3,088.8 and 1,577.9 mg/ kg respectively. Mice and rats of the control groups were administered once with 1% starch gel. For 14 days, the behavior and condition of the animals was monitored. The body weight of the experimental animals was measured on the 1st, 3rd, 7th, 9th and 14th days of the experiment.Results and discussion. Medium lethal doses of LD50 have been established for oral administration to laboratory animals. For mice, the LD50 was more than 5 986 mg/kg, i.e., according to the generally accepted hygienic classification, Altrick-Extra belongs to hazard class 4 (low-hazard substances). On rats, the LD50 was 3 103.1±48.5 mg/kg (2,354.6÷3,851.5 mg/kg). Therefore, Altrik-Extra belongs to hazard class 3 (substances are moderately hazardous).

The purpose of the research is to assess the acute oral toxicity of the drug Altrik-Extra in mice and rats, to determine its hazard class depending on the degree of exposure to animals.Materials and methods. White outbred mice and rats were used in the experiment. In the study of acute oral toxicity, conventional techniques were used.Results and discussion. Average lethal doses of LD50 were established when administered orally to laboratory animals. For mice, LD50 was more than 5986 mg/kg. Thus, according to the generally accepted hygienic classification (GOST 12.1.007-76), Altrick- Extra belongs to the 4th hazard class (low-hazard substances). In the study of acute oral toxicity in rats, LD50 was 3 103.1±748.5 mg/kg (confidence interval boundaries 2 354.6÷3 851.5 mg/kg). Therefore, in accordance with GOST 12.1.007-76, the studied drug belongs to the 3rd class of danger (moderately dangerous substances).

The purpose of the research is to define efficacy and to carry out titration of therapy dose of supramolecular complex of albendazole extra and triclabendazole in case of fasciolosis and gastro-intestinal nematodosis of sheep.Materials and methods. Testing the effectiveness of supramolecular complex of albendazole extra and triclabendazole based on low-molecular polymer polyvinylpyralidone-17 were carried out in the North Caucasian Federal District of the Chechen Republic from December 15 to December 30, 2018 on 65 sheep of the Tushino breed spontaneously infected by gastro-intestinal nematodes and Fasciola sp. Infected sheep were selected for the study based on the coproovoscopic studies by the Fulleborn’s method with the use of the ammonium nitrate solution. Selected sheep were divided into 5 groups based on matching criteria. 15 sheep of the first group were administered the preparation orally in a form of aqueous solution using a bottle in a dosage of 2.0 mg/kg of active substance (20 mg/kg of the preparation), second group – 4.0 mg/kg (40 mg/kg), third group – 5 mg/kg (50 mg/kg of the preparation). Fourth group of sheep was administered the mixture of triclabendazole and albendazole for the control (1 : 1 proportion), in a dosage of 4.0 mg/kg. Fifth group of five sheep was a clean control group and did not receive any preparations. After the administering of the preparation, clinical condition of the studied sheep was observed for three days. To determine the effectiveness of the preparation against Fasciola sp., after 8–10 days after the administration of the preparation, 5 sheep of each group were slaughtered for the helminthologic dissection of the liver. Also, the feces samples were collected from each animal and they were studied by the Fulleborn's method. Estimation of the efficiency of the drugs was performed by the method of "critical test" and helminthological dissection of the liver after slaughter according to the Guidelines approved by the World Association for the Progress of Veterinary Parasitology (1995).Results and discussion. Supramolecular complex based on albendazole and triclabendazole at a dose of 4.0 mg/kg (40 mg/kg in the preparation) once showed 100% effectiveness according to coproovoscopy and slaughter against mixed infection caused by Fasciola sp. and gastro-intestinal nematodes of sheep. This dosage was the lowest during which the high efficiency was shown and it was accepted by us as a therapeutic. The mixture of albendazole and triclabendazole at the same dosage showed less efficiency, 22.0 and 24.5 respectively. Thus, the high efficiency of the supramolecular complex against Fasciola sp. and gastrointestinal nematodes 5 times weaker in the therapeutic dosage was obtained. The advantage of the drug is that albendazole in it does not have an embryotropic effect.