RU2519085C1 - Antiparasitic agent for farm animals - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: agent comprises ivermectin, vitamin E, and organic solvents. The organic solvents are used as triethylene glycol and isopropyl alcohol. The components are contained in the following ratio, in wt %: ivermectin - 0.90-1.05, vitamin E - 0.01-0.02, isopropyl alcohol - 7.90-15.80, and 98% triethylene glycol up to 100.

EFFECT: invention enables to improve the efficiency of prevention and treatment of parasitic diseases of farm animals by reducing the toxic action, elimination of immunosuppression and adverse side effects while increasing antiparasitic activity of the agent, with the possibility of applying to lactating animals and use of meat without restrictions.

10 tbl, 14 ex

Description

The invention relates to veterinary parasitology and can be used for the prevention and treatment of parasitic diseases of farm animals.

A large number of drugs for the prevention and treatment of parasitic diseases containing compounds of various chemical classes and groups as active components are known. The most widely used drugs are the group of macrocyclic lactones, which include compounds of biological origin that belong to the class of avermectins. In chemical terms, avermectins are macrocyclic lactones (hydroxyl acid esters) isolated from soil microorganisms Streptomyces avermitilis. Their structure is based on a 16-element lactone ring connected at position 13 with elements of the carbohydrates-alpha-a-oleandrosil-alpha a-oleandrosil (Ivermectin and Abamectin. Ed. William C. Campbell, Springerverlag, New York, Berlin, Heidelberg, London, Paris, Tokyo, 1989, 363 p.).

Preparations of this class of antibiotics have a wide range of insecticidal, acaricidal and anthelmintic effects and are used as antiparasitic and anthelmintic agents (Putter I., MacConnel JD, Preiser FA et al. Avermectins: novel insecticides, acaricides and nematocides from a soil microorganism // Experient 1981; v. 37, p. 963-964). In veterinary practice, drugs based on the avermectin complex as a whole (aversectin) as well as formulations containing individual avermectins (abamectin, ivermectin, etc.) are used.

One of the most active compounds of the avermectin series is ivermectin (22,23-dihydroavermectin B1), consisting of the main component - 22, 23 - dihydroavermectin B _1a and the minor component - 22, 23 - dihydroavermectin B _1b , contained in the mixture in an amount of not more than 20 % As an active substance, ivermectin is part of the veterinary preparations Ivomek, Baymek, Novomek, Iversect, Ivertin, Ivermek, Ganamectin, Ivermag, etc. (Vidal Handbook Veterinarian , Moscow, 2011).

However, despite the high antiparasitic activity, most of the known drugs based on ivermectin are toxic and able to accumulate in milk, organs and tissues of animals. This creates the risk of ivermectins entering human food and restricts their use in lactating animals and for meat products. Slaughter for meat is permitted no earlier than 21-28 days after the last injection of ivermectin-containing preparations.

The first commercial drug developed on the basis of ivermectin is Ivomek (Merck, Sharp & Doum (USA)). Ivomec is a 1% sterile injection solution of ivermectin in a binary solvent mixture consisting of 40% glycerolformal and 60% propylene glycol (Campbell WC, Benz GW Ivermectin: a review of efficacy and safety // J. Vet. Pharm. Therap ., 1984, 7, p. 1-16).

The disadvantage of the drug Ivomek is its high viscosity, reaching 25-30 cP, which complicates the use of the drug in practice at low air temperatures. Injections of the drug cause pain in animals (especially sheep) due to the high content of propylene glycol, which are expressed in movements unusual for these types of animals (jumps, jumps) and impaired coordination of movement. Another disadvantage of the Ivomek preparation is the need for a sterilizing filtration stage in the manufacturing process of preparing a finished sterile dosage form. In addition, the drug cannot be used to treat lactating animals, because for 2 weeks it is excreted in milk and for a long time, it stays in the body for 21 days, limiting this period to the possible use of meat products. Slaughter of animals for meat treated with the drug Ivomek is permitted no earlier than 21 days later.

Known means for the prevention and treatment of parasitic diseases of animals, which is a solution of ivermectin in a mixture of polyethylene glycol-400, 80% ethyl alcohol and benzyl alcohol in the following ratio of components: ivermectin 0.8-1.2 g / 100 ml, polyethylene glycol 45-60 vol.%, 80% ethyl alcohol 35-45 vol.%, benzyl alcohol 2-10 vol.%. The antiparasitic agent is called Iversect (patent RU 2140737, A01N 27/00, publ. 10.11.1999).

The disadvantage of this tool is toxicity and prolonged excretion of processed animals from the body (more than 21 days), which leads to the impossibility of using the drug on lactating animals.

Also known is a preparation for the prevention and treatment of cattle hypodermatosis, containing ivermectin in an amount of 0.005-0.05 wt.%, Isopraponol - 10.0-50.0 wt.% And a solvent - triethylene glycol (up to 100.0 wt.%) . The content of the active component - ivermectin in the composition of the drug is several orders of magnitude lower than in traditionally used products. With subcutaneous administration, the drug is not excreted in milk and is rapidly excreted from the body (patent RU 2121831, A61K 31/00, publ. 11/20/1998).

A disadvantage of the known drug is a limited spectrum of antiparasitic action, because it is intended for the prevention and treatment of cattle hypodermatosis only.

Known antiparasitic drug for needleless administration in the treatment of farm animals, which is a solution of avermectins or their derivatives in organic solvents or their mixtures at a concentration of 2-35 g / 100 ml, while the preparation contains benzyl alcohol, ethyl alcohol, triethylene glycol as organic solvents, dimethyl sulfoxide or mixtures thereof (patent RU 2251421, A61K 31/70, publ. 05/10/2005).

The disadvantage of this drug is its use in high concentration (20%) and a dose of 0.4 mg per animal (80 mg of active substance), which makes the treatment unprofitable. This drug is recommended for use on lactating animals, however, its residual amounts are found in milk within 21 days in amounts from 0.12 to 0.60 ng / cm). In addition, a large number of components that make up its composition can also have a negative effect on the body of cattle. So, according to medical data, benzyl alcohol, which is part of drugs for humans, has a toxic effect on newborns and children under 3 years of age. Dimethyl sulfoxide used in medicine also has many contraindications: it is not recommended for use in case of impaired liver and kidney function, angina pectoris, myocardial infarction, severe atherosclerosis, glaucoma, cataracts, coma, pregnancy, lactation (medication guide 2011).

The closest analogue is the water-dispersed dosage form of ivermectin for the treatment of ecto- and endoparasitoses, including as a solvent water, dimethylamide or propylene glycol, or glyceroformal as a co-solvent, surfactants such as tween 80, solutol, cremophor or other polyoxyethylated natural derivatives oils as a micelle forming agent, benzyl alcohol or parabens as preservatives, phosphate-citrate buffer and additionally vitamin E (tocopherol) in the following content mponentov (.% by weight): active agent (ivermectin) - 0,1-7,5; cosolvent - 10-60; micelle forming agent (surfactant) - 4-20; preservative - 0.5-2.0; phosphate-citrate buffer pH 6-7 - up to 0.9, vitamin E - 0.7-7.0, distilled water - the rest (patent RU 2162699, A61K 35/70, publ. 02/10/2001).

The disadvantage of the closest analogue is the toxicity and prolonged excretion of processed animals from the body, which is unacceptable for use on dairy cattle. In addition, the increased content of vitamin E and the composition of the auxiliary components of the drug leads to suppression of the immune system, thereby increasing the risk of possible undesirable consequences. The need to use high doses of the drug for treatment (1.5 ml per 50 kg of body weight) also makes the use of this drug not cost-effective, and the use of intramuscular and subcutaneous routes of administration is highly costly both in time and cost.

The objective of the invention is to develop an effective and low-toxic drug for the prevention and treatment of parasitic diseases of animals with a wide spectrum of action, with the possibility of use on lactating animals and the use of meat without restrictions.

The technical result of the claimed invention is to increase the effectiveness of the prevention and treatment of parasitic diseases of farm animals by reducing toxic effects, eliminating immunosuppression and undesirable side effects while increasing the antiparasitic activity of the drug with the possibility of use on lactating animals and the use of meat without restrictions.

The technical result of the invention is achieved due to the qualitative and quantitative composition of the components, which are a composition of complementary action direction, significantly enhancing antiparasitic properties and reducing the toxicity of ivermectin.

The invention consists in the following: an antiparasitic agent for farm animals containing ivermectin, vitamin E and organic solvents, characterized in that it contains triethylene glycol and isopropyl alcohol as organic solvents in the following ratio of components (wt./vol.%):

Ivermectin - 1.00-1.05

Vitamin E - 0.01-0.02

99.8% isopropyl alcohol - 7.90-15.80

98% triethylene glycol - up to 100.

The applicant unexpectedly found that the antiparasitic agent, in combination and in the ratio of the components according to the present invention, when administered subcutaneously or intradermally due to its properties in relation to dissolution in the physiological region of the pH of the subcutaneous tissue, precipitates in the form of a stable complex and allows the creation of a “skin depot ″ , from which the active substance - ivermectin in the form of “boluses” enters the target organs and saturates them quickly and efficiently, bypassing uninterested organs. Larger molecules enter the lymphatic system because they cannot pass through the pores of the capillary wall. As a result, ivermectin fills the entire lymphatic system and enters the general circulatory system. Excipients of the antiparasitic agent - vitamin E, 98% triethylene glycol and 99.8% isopropyl alcohol provide the formation of a stable ivermectin complex with a prolonged duration of action and in addition to this increase the resistance of the host organism, preventing local reactions and detoxification.

The claimed composition of the antiparasitic agent can reduce toxicity, provide an effective dose at lower concentrations of the active substance and a single injection, as well as prevent the accumulation of ivermectin in milk and meat of animals.

An antiparasitic agent is used to treat and prevent parasitic animal diseases using intradermal administration to cattle in a dose of 0.4 ml per animal, preferably once. With severe invasions, the administration of the drug is allowed twice.

For cattle, the preparation according to the invention is used against nematodoses (teliasiosis, diktiocaulosis, trichocephaliasis, strongyloidosis, hematochiasis, ostertagiosis, nematodirosis, esophagostomiasis) and ectoparasites (psoroptosis, sarcoptosis, chorioptosis, and blood dysfunction). 1 ml / 50 kg bw subcutaneously, 0.5 ml per animal subcutaneously.

For pigs, it is used for nematodoses (metastrongylosis, ascariasis, esophagostomiasis, strongyloidosis) and against ectoparasites (sarcoptosis, hematopinosis) at a dose of 1 ml / 50 kg bw, 1.5 ml / 50 kg bw subcutaneously and 0.002 ml / kg bw intradermally.

For sheep used for nematodoses, psoroptosis in a dose of 1 ml / 50 kg bw subcutaneously.

The use of the antiparasitic agent according to the invention allows to obtain a high therapeutic effect against endoparasites and ectoparasites and keeps the concentration of the active compound in the milk of lactating animals below a level safe for human consumption, helps to accelerate the regeneration of damaged tissues, has a general strengthening effect on animals, ensures the safety of milk and meat when used in I write to people, reducing the financial and human costs of animal treatments.

The invention is illustrated by the following examples.

Example 1. Preparation of an antiparasitic agent.

Samples of ivermectin and vitamin E are added to the measured volume of isopropyl alcohol. The mixture is stirred until the ingredients are completely dissolved (if necessary, the mixture is heated to 35 ° C). Then, a measured volume of triethylene glycol is added to the resulting solution with stirring. The mixture is continuously stirred until complete homogeneity in the entire volume at room temperature (20 ° C) is achieved. The mixing time depends on the volume of the mixture, the type of mixer and its speed of rotation. The homogeneity of the solution is controlled by periodically sampling from the upper, middle and lower layers of the liquid in the mixing tank, followed by determining the density of the samples and the concentration of active substances in them.

Compositions of antiparasitic agents using different amounts of components are shown in table 1.

Tab. one The composition of the antiparasitic agent Ingredient Hitch / volume Content in the composition (% w / w) Composition A. Ivermectin 99% 1,030 kg 0.941 Vitamin E (oil form 98%) 15.0 g 0.014 Isopropyl alcohol (99.8%, density 0.79 t / cm ³ ) 8.69 kg 7,942 Triethylene glycol (98%, density 1.12, g / cm ³ ) 99.68 kg 91,103 Composition B

Ivermectin 99% 1,050 kg 0.986 Vitamin E (oil form 98%) 15 g 0.014 Isopropyl alcohol (99.8%, dens. 0.79, g / cm ³ ) 15.80 kg 14,841 Triethylene glycol, 98%, dense. 1.12 g / cm ³ ) 89.6 kg 84,159 Composition B Ivermectin 99% 1,060 kg 0.983 Vitamin E (oil form 98%) 15 g 0.014 Isopropyl alcohol (99.8%, density 0.79 g / cm ³ ) 12.64 kg 11,726 Triethylene glycol (98%, density 1.12 g / cm ³ ) 94.08 kg 87,277

Example 2. A production test of experimental series of antiparasitic agents against strongyloidosis and dictyocauliasis in cattle.

A test of the effectiveness of an antiparasitic agent was carried out in experiments on spontaneously infested heifers of a random age.

4 experimental groups of heifers of random age of 30 animals each, selected according to the results of coprological studies, and one control group were formed. Coprological studies of dictiocaulosis and strongyloidosis were carried out according to Berman's method in the modification of V.I. Shilova. The initial infection with strongylates ranged from 50% to 96.66%. The invasion of animals by dictiocaul with clinical signs was established: cough, lethargy, decreased appetite, minor mucous discharge from the nasal cavity were found in 30% of the animals.

For animals of groups 1 and 2, the antiparasitic agent according to the invention was injected subcutaneously once at a dose of 1 ml / 50 kg bw, 2 groups - 0.5 ml / 50 kg bw, 3 groups - once daily at a dose of 0.2 ml / head, 4 groups - intradermally once in a dose of 0.4 ml / head.

Animals of all groups were monitored for two weeks. In animals with clinical signs of diktiokauleza, the expiration, inhibition and cough practically stopped on the 4-5th day after the use of antiparasitic drugs in the above dosages. Coprological studies of fecal samples from animals after 2 weeks after treatment, dictiocaul larvae were not found. In the control group, they were found in 18 samples from 20 studied. The experimental results are presented in table 2.

Tab. 2 The results of studies of fecal cattle samples for strongyloidosis and dictiocaulosis before and after the use of the antiparasitic agent according to the invention Group number Samples Investigated Positive samples detected % Dose and route of administration Processing-tano goals Samples Investigated Positive samples detected % one. thirty 29th 96.66 subcutaneously 1.0 ml / 50 kg thirty thirty 0 one hundred 2. thirty fifteen fifty subcutaneously 0.5 ml / 50 kg thirty thirty one 96.67 3. thirty 10 33.33 intradermally 0.2 ml per head thirty thirty one 96.67 four. thirty 25 83.33 intradermally 0.4 ml per head thirty thirty 0 one hundred 5. twenty eighteen 90 not processed 0 twenty eighteen

A test of the claimed antiparasitic agent against strongyloidosis and dictyocaulosis of cattle showed its 100% effectiveness when administered subcutaneously at a dose of 1 ml / 50 kg bw and intradermally at a dose of 0.4 ml / head with a needleless injector.

Example 3. The effectiveness of the claimed antiparasitic agent for nematodoses in cattle was taken into account in the summer-autumn period of the region on 38 heifers with dictiocauliasis, 36 heifers for strongyloidosis, 44 heads of cattle for nematodirosis, 52 young animals for other strong digestive tract and 18 heads - with trichocephalosis. Invasive animals in the experiment were selected after preliminary studies of fecal samples by flotation using a saturated solution of zinc sulfate and a counting chamber to account for the number of nematode eggs in 1 g of feces.

The claimed antiparasitic agent was administered to cattle of the experimental groups once with dictyocauliasis at a dose of 10 μg / kg subcutaneously and 8 μg / kg intradermally, and with other nematodoses at a dose of 0.2 mg / kg, i.e. 1 ml per 50 kg of body weight. Animals of the control group did not receive the drug.

The effectiveness of the drug was taken into account according to the results of copro- and larvoscopic studies by the above methods before and after 18-20 days after deworming. The calculation of the effectiveness of the drug was carried out according to the type of “control test” according to the Guidelines approved by the World Association for the Progress of Veterinary Parasitology (1995).

The obtained test results of an antiparasitic agent for major cattle nematodoses are presented in table 3 and indicate the high effectiveness of the drug against different types of nematodes.

According to the results of coprological studies, a 100% decrease in the number of dictioca larvae in the feces of young cattle was obtained with subcutaneous administration at a dose of 10 μg / kg and intradermal administration at a dose of 8 μg / kg (0.4 ml / head). At the same time, after coughing the animals stopped coughing and their health improved. Infection of heifers in the control group during the experiment did not change significantly and amounted to 35.8 ± 3.7 ind. eggs in 1 g of feces, and at the end of the experiment 38.2 ± 4.1 specimens.

The effectiveness of the drug at a dose of 10 μg / kg with subcutaneous administration and 8 μg / kg (0.4 ml / head) intradermally with strongyloidosis of young cattle was 100%.

The effectiveness of the drug at a dose of 200 mcg / kg with nematodirosis was 99.2%, with strong gastrointestinal tract digestive tract - 99.5%, with trichocephalosis - 98.0%.

Infection of cattle in the control group did not change significantly during the experiment and amounted to before and at the end of the experiment: with strongyloidosis 70.4 ± 6.4 and 72.6 ± 6.3 ind. eggs, with nematodirosis - 139.8 ± 8.5 and 143.5 ± 8.4 specimens. eggs, with other strongilitis - 170.2 ± 9.0 and 174.0 ± 9.6 specimens. and trichocephalosis - 57.2 ± 5.0 and 59.6 ± 5.3 ind. in 1 g of feces.

Thus, the claimed antiparasitic agent at a dose of 10 μg / kg with a single subcutaneous injection and at a dose of 8 μg / kg (0.4 ml / head) with intradermal administration to cattle showed 100% efficacy in dictyocauliasis and strongyloidosis, and a dose of 200 mcg / kg subcutaneously 99.2% with nematodirosis, 99.5% with other strongilatoses of the digestive tract and 98.0% effectiveness with trichocephalosis. The drug was well tolerated by animals and did not cause side effects or local reactions.

Tab. 3 The effectiveness of the claimed antiparasitic agent for major nematodoses in cattle after a single injection Helminthiasis Group of animals Dose, mcg / kg Route of administration Number of goals Found eggs / larvae of nematodes in 1 g of feces, specimen. Efficiency% before treatment after treatment Dictation Experimental 8 VK 24 36.5 ± 3.8 0 one hundred Experimental 10 PC 24 37.3 ± 4.0 0 one hundred Control 0 - fourteen 35.8 ± 3.7 38.2 ± 4.1 - Strongyloidosis Experimental 8 VK eighteen 69.0 ± 6.0 0 one hundred Experimental 10 PC eighteen 68.7 ± 5.9 0 one hundred Control 0 - eighteen 70.4 ± 6.4 72.6 ± 6.3 - Nematodirosis Experimental 200 PC thirty 142.4 ± 8.6 1.2 ± 0.2 99,2 Control 0 - 2 139.8 ± 8.5 143.5 ± 8.4 - Other strongilatoses Experimental 200 PC 39 169.6 ± 9.3 1.0 ± 0.1 99.5 Control 0 - 13 170.2 ± 9.0 174.0 ± 9.6 Trichocephalosis Experimental 200 PC 12 54.5 ± 5.2 1.2 ± 0.2 99.5 Control 0 - 7 57.2 ± 5.0 59.6 ± 5.3 -

Example 4. A production test of experimental series of the claimed antiparasitic agent against subcutaneous bovine cattle.

The results of the commission test of the claimed antiparasitic agent for bovine hypodermatosis (spring chemotherapy) are presented in table 4.

Tab. four The results of the commission test of the claimed antiparasitic agent in spring chemotherapy for cattle hypodermatosis Group of animals Number of goals Dose, mcg / kg Hypoderm larvae were detected at the end of the experiment. EE,% IE,% number of animals number of larvae, ind./head Subcutaneous injection Experimental 140 10 0 0 one hundred one hundred Control twenty - twenty 11.3 ± 0.8 Intradermal Introduction Experimental one hundred 8 0 0 one hundred one hundred Control twenty 0 twenty 11.0 ± 0.8

The results obtained indicate the high effectiveness of the claimed antiparasitic agent for bovine hypodermatosis in spring chemotherapy. Received 100% efficacy of the drug at a dose of 10 μg / kg with subcutaneous administration and 100% intensity with intradermal administration at a dose of 8 μg / kg (0.4 ml / head).

The drug was well tolerated by animals and did not cause a local reaction. At the site of intradermal administration of the drug, a small bubble formed. After some time (6-10 hours), the bubble resolved. Animals were tied during treatment and did not show concern.

The results of commission tests of the claimed antiparasitic agents for early chemotherapy of cattle hypodermatosis are presented in table 5.

Tab. 5 The results of the commission test of the claimed antiparasitic agent for early chemotherapy of cattle hypodermatosis Group of animals Number of goals Dose, mcg / kg Hypoderm larvae were detected at the end of the experiment. EE,% IE,% number of animals number of larvae, ind./head Experimental 260 10.0 0 0 one hundred one hundred Control twenty - 9 11.5 ± 0.9

As follows from the results, the drug was 100% effective in early chemotherapy for cattle hypodermatosis. The tests showed the possibility of using the claimed antiparasitic agent for early and late chemotherapy of cattle hypodermatosis, both with subcutaneous and intradermal routes of administration.

Based on the results, we have established a therapeutic dose of the claimed agent in early chemotherapy for cattle hypodermatosis. For this, the drug was used subcutaneously and intradermally in different doses. The maximum effectiveness of the drug was achieved with subcutaneous and intradermal administration at doses of 12 and 10 μg / kg. So, 100% efficiency was obtained at a dose of 12 μg / kg for subcutaneous administration and at a dose of 10 μg / kg for intradermal administration using a needleless injector. The efficacy of the drug at a dose of 10 μg / kg with subcutaneous administration and 100% at a dose of 8 μg / kg with intradermal administration was also high. The drug was slightly lower at a dose of 8 μg / kg for subcutaneous administration and 6 μg / kg for intradermal administration (IE%, respectively, 97.48 and 96.93%, at 94.03 and 94.55% EE).

Thus, a dose of 10 μg / kg for subcutaneous administration and a dose of 8 μg / kg for intradermal administration are recommended by us as therapeutic for early chemotherapy for cattle hypodermatosis.

Example 5. The test of the effectiveness of antiparasitic drugs is carried out in experiments on heifers of random age and calves in farms unsuccessful for hypodermatosis. At the first farm, the claimed antiparasitic agent in doses of 0.3 ml and 0.5 ml per animal was administered, respectively, to 50 and 50 heifers subcutaneously in the lower third of the neck, once. Accounting processing efficiency was carried out six months after treatment. The processing efficiency was 88% and 100%, respectively. At the second farm, the claimed antiparasitic agent was administered subcutaneously at a dose of 0.5 ml per animal (5.0 - 10.0 - 20.0 μg / kg) in the region of the lower third of the neck to 110 cows, 20 heifers, 20 heifers of random age and 50 calves. The processing efficiency is in all cases 100%. On the third farm, 2 experimental groups and 1 control group were formed. An antiparasitic agent was injected intradermally in the neck area of 60 cows of the first experimental group at a dose of 0.2 ml (3.3-4 μg / kg body weight) and 70 cows of the second experimental group at a dose of 0.4 ml (6.6 - 8 μg / kg body weight) per animal (two injections of 0.2 ml) from a needleless injector. A small bubble formed at the injection site. His education was controlled visually or with a finger. After some time, the bubble resolved. The animals were tied up during treatment without any concern. Analysis was carried out one and two months after treatment. In two animals of the 1st experimental group, one larva of the subcutaneous gadfly was found (EE-97% and IE-99%). In one animal of the second experimental group, 2 larvae were found (EE-99% and IE-100%). In 20 control animals, 113 subcutaneous gadfly larvae were found. At the fourth farm, an antiparasitic agent was injected intracutaneously with a needle-free injector for cows with hypodermatosis.

The claimed agent was administered: 250 cows at a dose of 0.4 ml per animal, of which 45 were affected by stage 2 and 3 larvae, 98 larvae in total; 100 cows at a dose of 0.2 ml, of which 19 larvae were found.

A second examination was performed 20 days after treatment. All larvae detected after administration of the claimed antiparasitic agent died. No approach of new larvae and the formation of new nodules after application of the drug was noted.

Studies have shown the possibility of using the antiparasitic agent according to the invention for the prevention and treatment of cattle hypodermatosis with the intradermal route of administration using a needleless injector in doses of 0.2 - 0.4 ml per animal (3.3 - 8.0 μg / kg body weight ) with an efficiency of about 100%.

Example 6

The farm tested the declared antiparasitic agent for cattle teliasis. It was used along with the use of injectable hypodectin to combat bovine hypodermatosis, teliasiosis and dictyocaulosis.

The experiment was carried out on calves under the age of 1 year (4 groups of 20 animals each), who were diagnosed with teliasis on the basis of clinical signs and a positive laboratory study.

For the treatment of calves, the claimed antiparasitic agent was administered once in the following doses:

Group 1 - 20 goals - 0.5 ml per animal subcutaneously; 2nd group - 20 goals - 0.4 ml per head intradermally (0.2 ml at two points); 3rd group - 20 goals - the eyes of the animals were washed with 3% ichthyol emulsion daily for 10 days. 4th group - 20 goals - the eyes of the animals were washed with a 3% solution of boric acid, daily for 10 days. The effectiveness of the treatments was evaluated according to the results of a clinical examination and laboratory studies of conjunctival cavity swabs 10 days after the start of treatment. It was found that in groups 1 and 2, 10 days after its use, parasites were not detected. There were no clinical signs of the disease. No side effects or complications were noted. In the 3rd group, the clinical signs of the disease in animals disappeared, however, in 3 animals, single parasites were found in swabs from the conjunctival cavity. Side effects or complications when using a 3% ichthyol emulsion was not observed. In the 4th group, the clinical signs of the disease in animals disappeared, however, in 4 animals, single parasites were found in swabs from the conjunctival cavity. The effectiveness after application of the claimed antiparasitic agent was 100%. The efficiency of using a 3% ichthyol emulsion was 87%. The efficiency of using a 3% solution of boric acid was 89%.

Example 7. The test of experimental series of anti-parasitic anti-lice in pigs was carried out in the month of January in 18 sows infected with Haematopinus suis lice. Before using the drug, all animals were carefully examined taking into account the number of lice found. On the skin in the neck, back, scratches and scratches were noted. Pigs were divided into 2 groups: experimental (12 goals) and control (6 goals). The drug was administered to pigs subcutaneously at a dose of 0.2 mg / kg. The effectiveness of the drug was taken into account 7 days after treatment by taking into account the number of lice in animals of both groups.

Similar tests of the drug were carried out on the farm on 16 heads of cattle affected by N. bovis. The drug was administered subcutaneously, once at a dose of 0.2 mg / kg. Animals of the control group did not receive the drug.

In the experiment, there were 40 piglets aged 3-4 months weighing 40-50 kg, severely affected by lice Haematopinus suis and roundworms. Clinical signs: severe itching, scratching of the skin, anxiety, the presence of lice in animals. In the control group there were 10 piglets. Before using the drug, the animals of the two experimental and control groups were examined, and the number of lice in areas of 10 × 10 cm in the neck area was calculated.

The claimed drug when tested at a dose of 0.2 mg / kg in pigs had a 100% effect against Haematopinus suis, N. bovis (Table 6).

Tab. 6 The effectiveness of the claimed antiparasitic agent in a dose of 0.2 mg / kg for pig hematopinosis and cattle sifunculosis Group of animals Number of goals Multiplicity of processing The average number of lice per 1 animal, ind. Efficiency% before treatment after treatment Pigs Experimental 12 one 326.0 ± 13.4 0 one hundred Control 6 - 320.4 ± 12.7 327.2 ± 11.6 Cattle Experimental eleven one 143.4 ± 9.6 0 one hundred Control 5 - 147.2 ± 9.2 151.5 ± 9.5

Infection of animals from the control groups before the beginning and at the end of the experiment did not differ significantly and exceeded 320.4 ind./head in pigs and 143.4 ind./ head in cattle.

The test results of the drug at a dose of 0.2 mg / kg for sifunculosis (hematopinosis) in cattle also indicate 100% effectiveness of the drug.

Example 8. Testing experimental series of anti-parasitic anti-lice in cattle.

In the experiment there were 10 calves weighing 190-200 kg, severely affected by lice Haematopinus bovis. Clinical signs: severe itching, scratching of the skin, anxiety, the presence of lice in animals. There were 5 calves in the control group. Before using the drug, the animals of the experimental and control groups were examined, and the number of lice in areas of 10 × 10 cm in the neck area was calculated. After this, the animals of the experimental group were injected intradermally at a dose of 0.4 ml / head with a needleless injector. 7 days after administration, the animals were examined for lice. Not a single calf was found lice. Clinical signs of the disease disappeared completely. Animals gained weight, appetite appeared. The results are presented in table 7.

Table 7 The effectiveness of the drug against lice Group of animals Animal number The number of lice on the registration area of the skin of the calf (10 × 10 cm) Efficiency% Before introduction 7 days after administration experienced one 45 0 one hundred 2 67 0 one hundred 3 29th 0 one hundred four 38 0 one hundred 5 eighteen 0 one hundred 6 48 0 one hundred 7 9 0 one hundred 8 53 0 one hundred 9 44 0 one hundred 10 31 0 one hundred control one 59 67 2 61 71 3 17 28 four 43 46 5 22 33

The results showed 100% effectiveness of the drug when administered intradermally at a dose of 0.4 ml / head against lice in cattle.

Example 9. Testing of experimental series of antiparasitic agents for hematopinosis and ascariasis of pigs.

In the experiment we used 30 piglets aged 3-4 months weighing 40-45 kg, spontaneously infected with roundworms and lice. 3 groups of animals were formed with 10 animals each (two experimental groups and one control). The animals of the first group were injected with the antiparasitic agent according to the invention by the intradermal injection method using a needleless injection once at a dose of 0.02 mg / kg 0.002 ml / kg bw (0.02 mg / kg bw MD). The animals of the second group were injected with the antiparasitic agent of the invention subcutaneously at a dose of 1 ml / 50 kg bw. (0.2 mg / kg bw MT) once. Piglets of the third group were not processed. The effectiveness of the preparations was determined by the results of a clinical examination and detection of lice and nits on the body and hairline of piglets. Nematocidal efficacy was evaluated according to the results of helminthovoscopy of animal feces samples from the experimental and control groups before treatment and 14 days after treatment. The invasion of ascarids in the experimental and control groups ranged from 14 to 17 specimens / head. The effectiveness of drugs against lice and roundworms was 100%.

Example 10. The test of the claimed antiparasitic agent for sarcoptosis of pigs.

The test was performed on a pig farm on 66 pigs spontaneously infected with Sarcoptes suis. Pigs of the 1st, 2nd and 3rd experimental groups of 14 animals each were treated with the claimed drug, by subcutaneous injection of the drug at the base of the ear in a dose, respectively: 0.2; 0.3 and 0.4 mg / kg (1; 1.5 and 2.0 ml per 50 kg of mass) twice with an interval of 10 days. The effectiveness of the drug was determined by taking into account the number of detected ticks on the body surface with an area of 20 × 20 cm before and 10 days after the second treatment of animals. 12 pigs in the control group did not receive the drug.

The test results of the drug for pig sarcoptosis are presented in table 8 and indicate the difference in its effectiveness when used in different doses. The drug at a dose of 0.2 mg / kg showed insufficient effectiveness against Sarcoptes suis ticks, equal to 94.4%. 10 days after repeated treatment of pigs with the drug at a dose of 0.3 and 0.4 mg / kg, 100% efficiency was obtained. The optimal dose was 0.3 mg / kg, i.e. 1.5 ml of solution per 50 kg of body weight. It should be noted that after treatment, the itching in pigs stopped. No live ticks were found in scrapings of the skin; restoration of the affected inflammatory areas of the skin was observed.

Tab. 8 The effectiveness of the drug in sarcoptosis of pigs Group of animals Number of goals Dose mg / kg Multiplicity of treatments The average number of ticks in one animal (20 × 20 cm ² ), ind. Efficiency% before treatment after treatment Experimental fourteen 0.2 2 11.3 ± 0.8 0.78 ± 0.1 94.4 Experimental fourteen 0.3 2 11.6 ± 0.7 0 one hundred Experimental fourteen 0.4 2 12.0 ± 0.7 0 one hundred Control 12 11.5 ± 0.6 12.4 ± 0.8

Example 11

The experiment was performed on 18 sows in which ear scabies was installed (back of the ears, part of the neck). Sick animals had clinical manifestations: anxiety, constant scratching of the affected areas of the skin on the feeders and septa. The claimed antiparasitic drug was administered to sick animals subcutaneously in the neck in the following doses: 200, 300, 500, 750, 1000 and 1500 μg / kg of body weight, 3 sows per dose. No changes were noted at the injection sites and from the general condition of the animals. 14 days after the administration of the drug, a re-examination of the sows was carried out. In all animals, the itching completely stopped, inflammatory processes from the neck and auricle disappeared, the crusts completely disappeared and normal healthy skin formed in their place. In repeated scrapings, ticks were not found. Studies have shown that this drug in tested doses showed 100% effectiveness in pig sarcoptosis.

Example 12. The effectiveness of an antiparasitic agent for cattle psoroptosis was studied on 40 heads of cattle spontaneously infected with Psoroptes bovis ticks. In animals, clinical signs of psoroptosis were noted: lesions at the base of the horns, at the root of the tail, scab on the sacrum, combs. Cattle were divided into 2 groups and numbered. The drug was administered to 18 animals of the first group at a dose of 0.2 mg / kg according to ivermectin at the rate of 1 ml per 50 kg of body weight, subcutaneously once. 14 animals of the second group were treated with an interval of 8 days. The drug was injected into the neck in compliance with the rules of asepsis and antiseptics. During the experiment, cattle were kept indoors. Animals of the control group (8 animals) did not receive the drug. Acaricidal activity of the drug was taken into account according to the results of laboratory studies of skin scrapings from the affected areas of the body (on the border with the healthy one) in order to take into account the number of ticks before and 4 weeks after drug administration compared to the number of ectoparasites in animals of the control group (“control test”).

The test results are presented in table 9.

Tab. 9 The effectiveness of the claimed antiparasitic agent for psoroptosis in cattle Group of animals Number of goals Dose mg / kg Multiplicity of treatments The average number of ticks in one animal, ind./head Efficiency% to experience after experience Experimental eighteen 0.2 one 13.0 ± 1.5 0.55 ± 0.1 96.08 Experimental fourteen 0.2 2 12.8 ± 1.6 0 one hundred Control 8 13.2 ± 1.6 14.0 ± 1.7

When a commission test of the claimed funds in the case of the clinical manifestation of psoroptosis in cattle, 100% efficiency was obtained with subcutaneous double administration with an interval of 8 days at a dose of 0.2 mg / kg

Example 13. The effectiveness of the claimed funds for psoroptosis of sheep was studied in the Astrakhan region in December on 40 sheep affected by ticks Psoroptes ovis. Sheep were divided into 3 groups of 10 animals each. Sheep of the 1st, 2nd and 3rd experimental groups were injected subcutaneously in doses, respectively: 0.1; 0.2 and 0.3 mg / kg based on 0.5; 1.0 and 1.5 ml of solution per 50 kg of body weight twice with an interval of 8 days. The effectiveness of the drug was determined by examining scrapings from the site of skin lesion (on the border with the healthy one) before and 10 days after the second injection of newmek. The calculation of the effectiveness of the drug was carried out according to the type of “control test”. Under the magnifying glass, the number, stages of development of ticks and their condition were determined.

The test results of the drug for sheep psoroptosis, are presented in table 10, indicate a different degree of effectiveness of the drug in different doses. 10 days after repeated subcutaneous administration of the drug at a dose of 0.1 mg / kg, only 6 out of 10 treated sheep were freed from ticks. The number of Psoroptes ovis ticks decreased by 94.8%.

100% efficacy of the drug against ticks of P. ovis was obtained by testing it at a dose of 0.2 mg / kg. In all 10 treated sheep, ticks were not found.

High efficacy of the drug was obtained with psoroptosis of sheep at a dose of 0.2 mg / kg when applied twice with an interval of 8 days. 10 treated sheep were completely free of P. ovis. The effectiveness of the drug in this dose was also 100%. In the affected areas of the skin, signs of inflammation disappeared, and crust rejection was noted.

Tab. 10 The effectiveness of the drug for psoroptosis in sheep Group of animals Number of goals Dose mg / kg Multiplicity of treatments The average number of ticks in one animal, ind. Efficiency% before treatment after treatment Experimental 10 od 2 9.7 ± 0.7 0.6 94.8 Experimental 10 0.2 2 10.1 ± 0.8 0 one hundred Experimental 10 0.3 2 9.9 ± 0.7 0 one hundred Control 10 10.4 ± 0.8 11.6 ± 0.9

Example 14. Determination of residual ivermectin after treatment with the claimed antiparasitic agent.

The study of residual amounts of active substances of the claimed antiparasitic funds is carried out on 3 cows. Sampling of milk is carried out before the introduction of the drug and after 1, 3, 6, 12, 24, 36, 48, 60, 72 hours, 5, 7, 10, 14, 21, 28 days after drug administration. This scheme allows obtaining adequate profiles of the residual concentration-time concentration of ivermectin.

The determination of ivermectin in samples of cow's milk was carried out by chromatography-mass spectrometry.

As a result of the study, ivermectin in the range of concentrations available for measurement (> 10 ng / ml of the sample) was not detected in the samples of cow's milk. The obtained results of the study of milk samples for the content of residual amounts of ivermectin after treatment of lactating cows with an antiparasitic agent at a dose of 0.4 ml per head using the intradermal route of administration make it possible to recommend it for treating cattle in the above dose and method of administration without restrictions.

The determination of the presence of residual amounts of this drug in the internal organs and muscles was carried out at the same time intervals. To conduct the experiment, the experimental and control groups of calves are formed in the amount of 24 heads according to the principle of analogues. The antiparasitic agent according to the invention was injected with a needle-free mechanical injector BI-7M into the neck area twice in 0.2 ml. The injection site is shaved and disinfected.

At the end of the experiment, all experimental and control animals were simultaneously slaughtered. Samples of biological material were taken from them (muscles, liver, kidneys, lungs, heart, adipose tissue). The determination of ivermectin residues was carried out by the same procedure as in milk. The data obtained indicate that no ivermectin residues are found in the biological material. So, with the subcutaneous method of administering the studied antiparasitic agent at a dose of 3 ml per head (0.3 mg / head), residual amounts in meat in microdoses are not detected already on the 5th day. The use of an antiparasitic agent using the intradermal route of administration at a dose of 0.4 ml per head (4 mg / head) ensures its rapid excretion.

Claims (1)

Antiparasitic agent for farm animals containing ivermectin, vitamin E and organic solvents, characterized in that it contains triethylene glycol and isopropyl alcohol as organic solvents in the following ratio, in mass / volume. %:
ivermectin 0.90-1.05
Vitamin E 0.01-0.02
99.8% isopropyl alcohol 7.90-15.80
98% triethylene glycol to 100.