RU2627893C1 - Method of production of a combined antihelmint tablet with a symbiotic treatment for treatment of a small cattle - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: invention is a method for producing a combined anthelmintic tablet with a symbiotic for treating small cattle containing a first and second layer comprising the steps of: adding a first powder mixture to a mould plate. Mentioned first powder mixture contains a pharmaceutically active substance and a binder, a second powder mixture is added to said mould plate. Mentioned second powder blend comprises a binder and the composition of mentioned second powder blend is different from the composition of mentioned first powder mixture, the first powder mixture and the second powder blend are pressed on said plate of the mould to form a tablet form and subjected to said tableted form with radio frequency emission for a period of Time sufficient to activate said binder within said tablet mould to fuse mentioned tableted Th form into said tablet, such that the density of mentioned tablet is less than about 0.8 g/cm³, characterized in that a bacterial concentrate is prepared for the preparation of the first powder mixture comprising a bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LH-1 consortium with a titre of 108-1010 CFU/g sorbed on a carrier in a ratio of 1:1:12, which Is concentrated by filtration or centrifugation to a suspension containing 5 billion bacteria per ml, followed by mixing them in equal volumes. As the carrier, flour or bran is used at the rate of 12 parts of the support per part of a mixture of concentrated cultures, and then the obtained dry powder mass is mixed with lactulose, and to obtain the second powder mixture, ivermectin, praziquantel and at least one pharmaceutically acceptable excipient microcrystalline cellulose MCC is used, then the substances ivermectin, praziquantel and excipient are mixed in dry kind. The components in the tablet are in a certain ratio in wt %.

EFFECT: invention provides high anthelmintic activity, intensification of treatment and prevention of a number of helminthic invasions, nonspecific correction of the immune response of the animal organism, normalization of hepatoprotective and reparative liver functions.

6 ex, 1 tbl, 1 dwg

Description

FIELD OF THE INVENTION

The invention relates to veterinary medicine, in particular, to a method for the production of a combined anthelmintic tablet with a symbiotic for the treatment of small cattle and can be used for the prevention and treatment of helminthic invasions, non-specific correction of the immune response of animals, normalization of hepatoprotective and reparative functions of the liver on the effects of chemotherapeutic agents and helminthic invasions of the body of small cattle.

State of the art

Known complex antiparasitic drug that does not have immunosuppression, including avermectin complex and excipients, while it additionally contains an immunostimulant ribotan in the following ratio of components, mass. %: avermectin complex 05-2.0; ribotan 5.0-15.0; excipients - the rest.

In the complex antiparasitic preparation, as an avermectin complex, it contains either Avertin N, or Aversectin C, or Ivermectin, or Abamectin, or others.

The complex antiparasitic preparation includes an avermectin complex from Streptomyces avermitilis VKPM S-1440 mycelium with an increased content of group B (see Pat. RU No. 2155052, IPC A61K 35/70, publ. 08.27.2000).

The disadvantage of this drug is a narrow, anti-nematode effect, while the drug of the macrocyclic lactone group is not effective for controlling the helminths of the genera of cestodes and trematodes, for which it is necessary to use additional anthelmintics.

Known drug for the prevention and treatment of helminthiases of horses, containing a compound from the group of avermectins and targeted additives, while it additionally contains praziquantel or phenasal in the following ratio of components, mass. %: compound from the group of avermectins 0.05-10.0; praziquantel or phenasal 3.0-70.0; targeted additives - the rest.

In the preparation for the prevention and treatment of horse helminthiases, the compound from the group of avermectins contains ivermectin, or abamectin, or doramectin, or moxidectin (see Pat. RU No. 2279874, IPC A61K 31/00, A61K 31/495, A61K 36/06, published on July 20, 2006).

The disadvantage of this drug is that it has limited capabilities, only for the treatment of horses.

A known method for the treatment of helminthiases of ruminants, including the oral administration to small and cattle of a drug containing praziquantel and ivermectin, while sodium selenite, nipagin, nipazole, lactose, tween-80, gelatin and distilled water are added to the composition of the drug the ratio of ingredients (wt.%): praziquantel - 5.0 ivermectin - 0.2, sodium selenite - 0.071, nipagin - 0.01, nipazole - 0.005, lactose - 30.0, tween - 80-2.0, gelatin - 2.0, distilled water - the rest, then cooked ekarstvennoe means in the form of a slurry, which is administered to the animals once a rate of 1 ml per 10 kg of animal weight.

In a method for treating ruminant helminthiases, a suspension in the form of a drug is administered to animals individually by force on the root of the tongue.

A medicine for treating helminthiases of ruminants according to the method according to any one of claims. 1 and 2, containing praziquantel and ivermectin, additionally contains sodium selenite, nipagin, nipazole, lactose, tween-80, gelatin and distilled water in the following ratio of ingredients (wt.%): Praziquantel - 5.0, ivermectin - 0.2, sodium selenite - 0.071, nipagin - 0.01, nipazole - 0.005, lactose - 30.0, tween-80 - 2.0, gelatin - 2.0, distilled water - the rest (see US Pat. RU No. 2412697, IPC A63K 31/00, А61Р 33/10, publ. 02/27/2011).

The disadvantage of this method and the drug is that it has a high anthelmintic efficacy against major helminthiases, however, sodium selenite, which is part of the product, does not protect the animal organism from toxic effects on the liver of the drug and helminth decomposition products (see Kolosova O.V. Morphological changes in the liver of healthy minks under the influence of an aqueous solution of sodium selenite with a prolongator. OV Kolosova Bulletin of the Krasnodar GAU. 2011. No. 1 - p. 137-141).

Known drug for the prevention and treatment of helminthiases in animals, containing a compound from the group of avermectins or its salt and the target additive, while it additionally contains praziquantel in the following ratio of ingredients, mass. h.: compound from the group of avermectins: pyrantel or its salt: praziquantel: target additive = 1.2: 3.0: 1.0: 6.0.

The drug as a compound from the group of avermectins contains ivermectin, or abamectin, or doramectin, or moxidectin.

The preparation as a pyrantel salt contains pyrantel pamoate, or pyrantel tartrate, or pyrantel embonate, or pyrantel hydrochloride (see Pat. RU No. 2496329, IPC A23K 1/16, publ. 10.27.2013).

The disadvantage of this drug is that it does not have a pronounced antiviral activity, as well as the need for its long-term use in treatment.

The closest in technical essence and the achieved positive effect and adopted by the authors for the prototype is a method of manufacturing a tablet containing the first and second layer, comprising the steps of: adding the first powder mixture to the mold plate, said first powder mixture containing a pharmaceutically active substance and a binder, add a second powder mixture to said mold plate, said second powder mixture containing a binder and the composition of said second the powder mixture differs from the composition of the specified first powder mixture, the first powder mixture and the second powder mixture are pressed on the specified mold plate to form a tablet form and the specified tablet form is subjected to radio frequency radiation for a period of time sufficient to activate the specified binder inside the specified tablet molds for fusing said tablet form into said tablet so that the density of said tablet is less than about 0.8 g / cm ³ and the specified tablet was absorbed in the oral cavity when placed on the tongue for less than about 30 seconds.

In a method in which said binder in said first powder mixture and said binder in said second powder mixture are fusible materials with a melting point of from about 30 ° C to about 140 ° C and said tablet form is exposed to said radiation for a period time sufficient to melt or soften said binders.

In a method in which said binder in said first powder mixture is a binder melted by RF radiation, and said tablet form is exposed to RF radiation for a time sufficient to melt or soften said binder melted by RF radiation.

In a method in which said first powder mixture contains material heated by RF radiation, and said tablet form is exposed to RF radiation for a period of time sufficient to heat said material heated by RF radiation, so that said material heated RF radiation, melted or softened the specified binder, which is part of the specified first powder mixture.

In a method in which said binder in said first powder mixture and said binder in said second powder mixture are water-activated binders, said first powder mixture and said second powder mixture additionally containing water-containing materials, and said tablet form is subjected to the specified exposure to radiation for a period of time sufficient to heat the water-containing materials above their dehydration temperature.

In a method in which said first powder mixture comprises particles comprising said first pharmaceutically active substance, said particles being coated with said binding agent.

In a method comprising the step of compressing said first powder mixture before adding said second powder mixture to said mold plate.

In a method in which the surface of said tablet is further exposed to infrared radiation, wherein most of the wavelength of said infrared radiation is from about 0.5 to about 5 microns.

A tablet obtained in accordance with the method according to the above items, comprising a first layer and a second layer, wherein:

- said first layer contains a pharmaceutically active substance, and the composition of said first layer is different from the composition of said second layer;

- the density of the specified tablets is less than approximately 0.8 g / cm ³ ;

- and the resorption of the indicated tablets in the oral cavity when placed on the tongue takes less than about 30 seconds.

A tablet in which said first layer does not contain the same pharmaceutically active substance as said second layer.

A tablet in which said first layer dissolves at least two times faster than said second layer.

A tablet in which the color of said first layer is different from the color of said second layer.

A tablet in which the taste of said first layer is different from the taste of said second layer.

A tablet containing a third layer, wherein the composition of said third layer is different from the composition of said first layer and said second layer.

A tablet whose density is less than about 0.7 g / cm ³ .

A tablet in which said binder contains polyethylene glycol with an average particle size of less than about 100 microns.

A tablet containing less than about 1 weight. % super baking powder (see US Pat. RU No. 2578950, IPC A61K 9/24, A61K 9/14, A61K 31/00, A61K 47/34, A61J 3/10, B29C 43/52, B30B 11/02, B30B 11 / 00, published March 27, 2016).

The disadvantage of this multilayer tablet is the complexity of production, as well as the fact that it does not have a pronounced antiviral activity and the need for long-term use in treatment.

Disclosure of invention

The objective of the invention is to develop a method for the production of a combined anthelmintic tablet with a symbiotic for the treatment of small cattle with high anthelmintic activity, non-specific hepatoprotective, immunostimulating and adaptogenic properties, which helps to intensify the treatment and prevention of a number of helminthic invasions, accompanied by a decrease in immunobiological properties of the body properties of the liver using rational ems which provide effective preparation of tablets due to combined use of a combination dosage tablet antiparasitic effective components.

The technical result that can be achieved using the present invention is reduced to the high anthelmintic activity of the tablet, the intensification of treatment and prevention of a number of helminthic invasions, non-specific correction of the immune response of the animal organism, normalization of the hepatoprotective and reparative functions of the liver.

The technical result is achieved using a method of manufacturing a combined anthelmintic tablet with a symbiotic for treating small cattle, comprising a first and second layer, comprising the steps of: adding a first powder mixture to a mold plate, said first powder mixture containing a pharmaceutically active substance and a binder, add a second powder mixture to said mold plate, said second powder mixture containing a binder, and the composition indicated the second powder mixture differs from the composition of the specified first powder mixture, the first powder mixture and the second powder mixture are pressed on the indicated mold plate to form a tablet form, and the specified tablet form is subjected to radio frequency radiation for a period of time sufficient to activate the specified binder inside the specified tablet form for fusing the specified tablet form in the specified tablet, so that the density of the specified tablets comp it was less than about 0.8 g / cm ³ , and to obtain the first powder mixture, a bacterial concentrate was prepared, including a consortium of bifido and lactobacilli Bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LG-1 with a titer of 10 ⁸ -10 ¹⁰ CFU / g sorbed on the carrier in a ratio of 1: 1: 12, which is concentrated by filtration or centrifugation to obtain a suspension containing 5 billion bacteria in I ml, followed by mixing them in equal volumes, moreover, flour or bran are used as a carrier based on 12 parts of the carrier per I part of the mixture of concent sorbed cultures, contact-sorption drying of biomass is carried out, and then the obtained dry powder mass is mixed with lactulose, and ivermectin, praziquantel and at least one pharmaceutically acceptable excipient are used as the second powder mixture, using microcrystalline cellulose MCC, then mix the substances of ivermectin, praziquantel and filler in dry form in the following ratio of mass components. %:

ivermectin 0.27-0.28 praziquantel 7.00-7.14 consortium of bifido and lactobacilli (Bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LH-1) with a titer of 10 ⁸ -10 ¹⁰ CFU / g sorbed on the carrier in a ratio of 1: 1: 12 35.00-35.71 lactulose 21.00-21.43 microcrystalline cellulose MCC 35.00-35.44

Helminthiases of ruminants are widespread everywhere and present a serious problem in animal husbandry, since they cause enormous economic damage to farms (see Kolesnikov VI, “An Integrated System of Technological Processes for the Prevention of Basic Sheep Helminthiases,” Kolesnikov VI, Vestnik APK Stavropol. 2015. No. 1 (17) S. 103-106); (see Lopteva M.S., Kolesnikov V.I. Economic damage during dicroceliosis // Veterinary Service of the Stavropol Territory. 2010. No. 1. P. 36-39); (see Safiullin RT. Distribution and economic damage from the main ruminant helminthiases // Veterinary medicine. - 1997. - No. 6. - P. 28-32), in this regard, the prevention and treatment of ruminant helminthiases is very relevant. Currently, there are a large number of drugs for the fight against helminthiases, including from the group of macrocyclic lactones (see Arkhipov I.A. Anthelmintics: pharmacology and use. Publishing house of the Russian Academy of Agricultural Sciences. M. - 2009. - 409 p.); (see Ataev AM, “Comparative efficacy of anthelmintics in sheep helminthiases,” Ataev AM, Zubairova MM, Kolesnikov VI, Beatti AM, Eldarova L.Kh. / Bulletin of Veterinary Medicine. 2016. No. 1 (76). S. 50-54).

Ivermectins are widely used in veterinary practice, in numerous studies have proven effective in the fight against ecto and endoparasites of farm animals (see Lopteva M.S., Kolesnikov V.I. Economic damage in dicroceliosis // Veterinary Service of Stavropol. 2010. No. 1. S. 36-39); (see Kolesnikov V.I. “Efficiency of a new drug of prolonged action“ IVERONG 2 ”for sheep strongilitis) / Kolesnikov V.I., Engasheva E.S., Suslov V.V., Koshkina N.A., Kits E. A., Lopteva M.S., Filimonov D.N. Regulatory issues in veterinary medicine. 2015. No. 4. P. 95-98).

Thus, the technical result is achieved through the combined use of a combination of effective antiparasitic components in a medicine tablet, that is, a medicine tablet contains antagonistically active bacteria of normal intestinal flora, and a bacterial reproduction stimulator, thereby achieving non-specific correction of the animal’s immune response, restoration of functional activity, and acceleration of hepatocyte regeneration metabolic and reparative processes in the tissues of the liver with helminthic invasions When the anthelmintic substances are exposed to the liver, while ivermectin and Praziquantel are used as an anthelmintic, a mixture of a bifido consortium and lactobacilli sorbed on a plant carrier is introduced as bacteria, and the tablet contains lactulose as a stimulant of bacterial growth The formative substance of the tablet contains microcrystalline cellulose (MCC).

The components are formed into tablets, while one tablet contains anthelmintic substances ivermectin and praziquantel, bacteria of the normoflora of the intestine, a stimulator of bacterial reproduction and a formative substance.

Ivermectin (Ivermectin), code CAS 70288-86-7, a white or light yellow crystalline powder, has a pronounced antiparasitic effect on the larval and mature stages of the nematodes of the gastrointestinal tract and lungs, larvae of the subcutaneous, nasopharyngeal and gastric gadfly, lice, bloodsucker and sarcoptoid ticks. Ivermectin stimulates the release of gamma-aminobutyric acid (GABA) by the nerve endings and enhances its binding to synaptic GABA receptors, blocking the transmission of nerve impulses, which leads to paralysis and subsequent death of helminths. In ticks and insects, transmission of nerve impulses between nerve endings and muscle cells is blocked, which also leads to paralysis and death of parasites.

Praziquantel (Praziquantel), code CAS 55268-74-1, white crystalline powder, bitter in taste. Hygroscopic, readily soluble in chloroform and dimethyl sulfoxide, soluble in ethanol and very slightly soluble in water. A broad-spectrum anthelmintic agent is effective against cestodoses and trematodoses. Increases the permeability of helminth cell membranes for calcium ions, causing a generalized contraction of the muscles of the parasite, which turns into persistent paralysis, leading to the death of the helminth (see www.rlsnet.ru \ mnn_index_id_244.htm).

Microcrystalline cellulose (MCC) TU 9199-001-07508109, a free-flowing snow-white powder with a crystallinity of 70-85% and an average crystal length of 7-10 nm, odorless and tasteless. MCC are obtained by fine grinding and thorough cleaning of cotton cellulose.

MCC is used in the pharmaceutical and food industries, in medicine, both as a food additive and as an inert filler for tabletting drugs.

A tablet with the addition of MCC is distinguished by an easy release of medicinal substances, permissible limits of weight variation, and mechanical strength. Chemically and physically stable, has excellent compressibility (see http://www.rlsnet.ru/mnn_index_id_2245.htm).

The biomass that is part of the product contains bifidobacteria, both strains are certified and deposited at the All-Russian State Research Institute for Control, Standardization and Certification of Veterinary Medicines (VGNKI), Bifidobacterium adolescentis B-1, B-2944 strain or Lactobacillus lactobacillus Lophobac strain Lophobac -1, B-5863, or a mixture thereof, adsorbed on a carrier. Natural and artificial substances suitable as sorbents for bacteria, in particular, colloidal silicon dioxide, activated carbon, hydrolysis lignin, and others, can be used as a carrier.

The biomass is made from living bacteria, is a homogeneous, free-flowing, bran-shaped or flour powder (12 parts by weight of the carrier and one part by volume of a mixture of concentrated dried cultures). The moisture content is not more than 8%, the amount of carotenoids is not less than 0.24 mg per 1 g, the amount of beta-carotene is not less than 0.1 mg in 1 g.

In the state adsorbed on the carrier, the bacteria provide a high local colonization of the intestinal mucous membranes and enhance the recovery processes in them.

The strains used are non-toxic, non-virulent, non-toxic to humans and animals, have high antagonistic activity to conditionally pathogenic microorganisms, interfere with their adhesion to the intestinal mucosa, promote normalization of the microbiocenosis of the gastrointestinal tract and increase non-specific resistance of the body, activate parietal digestion, activate parietal digestion, digestion, and parietal digestion have an immunomodulatory effect.

The hepatoprotective effect of bifidobacteria and lactobacilli is due to the following:

- under the influence of these bacteria, the pH in the large intestine decreases due to the fermentation of polysaccharides with the formation of fatty acids. At low pH, bacterial degradation of primary bile acids (cholic and deoxycholic) is suppressed, which leads to a change in their intestinal-hepatic circulation and suppression of the synthesis of bile acids in the liver;

- the microflora of the digestive tract, in particular saprophytic, prevents the absorption of cholesterol from the digestive tract;

- bifidobacteria reduce the output of cholesterol from liver cells by inhibiting the activity of HMG-CoA reductase;

- lactobacilli, by isolating a large amount of lactic acid and lowering the pH of the medium, deconjugate bile acids, which bind cholesterol at acidic pH values;

- with an acidic reaction of the medium in the intestine, the osmotic pressure increases, due to the metabolites of bifidobacteria and lactobacilli, the retention of ammonium ions in the intestine increases, the migration of ammonia from the blood into the intestine and its ionization;

- bifidobacteria and lactobacilli transform exo- and endotoxins to form compounds that are not absorbed in the intestine.

After taking bifidobacteria, the pH in the large intestine decreases, the bacterial degradation of primary bile acids is suppressed, which leads to a change in their intestinal-hepatic circulation and, as a result, suppression of the synthesis of bile acids in the liver. This, in turn, inhibits the formation of cholesterol in the liver and leads to a decrease in serum cholesterol. A decrease in blood lipids reduces the load on damaged hepatocytes, helping to reduce cholestasis.

Lactulose (Lactulose) is a synthetic disaccharide not found in nature, in which each galactose molecule is connected by a p-1,4-bond with a fructose molecule. The action of lactulose is determined by the fact that its molecules are not broken down by enzymes, as a result of which it remains intact until it enters the large intestine, where bacteria decompose into organic acids, mainly lactic, acetic, butyric and propionic. As a result, the intestinal contents are acidified and the osmotic pressure in the colon increases. The hepatoprotective effect of lactulose is mediated, and is due to a decrease in the concentration of ammonia due to acidification of the contents of the colon, inhibition of urea decomposition by bacteria. Lactulose promotes the growth of bacteria of normal intestinal microflora and improves liver function, has been successfully used as a filler for direct compression of tablets (see http://www.rlsnet.ru/mnn_index_id_1041.htm).

The essence of the method of production of a combined anthelmintic tablet with a symbiotic for the treatment of small cattle is as follows.

To make a two-layer tablet, first the first powder mixture (symbiotic) is added to the mold plate, then the second powder mixture (anthelmintics). The first powder mixture contains a pharmaceutically active substance and a binder. The second powder mixture contains a pharmaceutically active substance and a binder. Next, the first powder mixture and the second powder mixture are pressed onto the mold plate to form a tablet form, which is subjected to radio frequency radiation for a period of time sufficient to activate the binder and fuse the tablet form into a two-layer tablet. The density of the tablets is at least 0.8 g / cm ³ . A tablet dosage form is prepared containing the anthelmintic substances ivermectin (Ivermectin) and praziquantel (Praziquantel), bacteria of the normoflora of the intestines of lactobacilli and bifidobacteria (adsorbed on a plant carrier), a stimulator of the reproduction of bacteria of lactulose (Lactulose) and a crystalline co-forming substance components in dry form mass. %:

ivermectin 0.27-0.28 praziquantel 7.00-7.14 consortium of bifido and lactobacilli (Bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LH-1) with a titer of 10 ⁸ -10 ¹⁰ CFU / g sorbed on the carrier in a ratio of 1: 1: 12 35.00-35.71 lactulose 21.00-21.43 microcrystalline cellulose MCC 35.00-35.44

Before use, the required number of tablets is diluted in a volume of water for subsequent dissolution and formation of a suspension, which, in accordance with the dosage, is forcibly injected into the root of the tongue with the help of a metering syringe.

Brief description of drawings and other materials

The drawing shows a method for the production of a combined anthelmintic tablet with a symbiotic for treating small cattle, an assessment of the immunostimulatory activity and effect on the liver of a combined two-layer anthelmintic tablet with a symbiotic on day 10 after administration of the drug, table.

Disclosure of invention

Examples of specific performance of the production method of a combined anthelmintic tablet with a symbiotic for the treatment of small cattle

Example 1. A method of manufacturing a combined anthelmintic tablet with a symbiotic for treating small cattle is carried out as follows: first a powder mixture (symbiotic) is applied to the mold plate, then a second powder mixture (anthelmintic), the first powder mixture containing a pharmaceutically active substance and a binder. The second powder mixture contains a pharmaceutically active substance and a binder. The composition of the second powder mixture is different from the composition of the first powder mixture. Next, the first powder mixture and the second powder mixture are pressed onto the mold plate to form a tablet form, which is subjected to radio frequency radiation for a period of time sufficient to activate the binder and fuse the tablet form into a two-layer tablet. The density of the tablets is at least 0.8 g / cm ³ . Examples of binders include, but are not limited to, fusible binders and water-activated binders. The carrier contains one or more suitable excipients for the preparation of tablets. Examples of useful excipients include, but are not limited to, fillers, adsorbents, disintegrants, lubricants, lubricants, sweeteners, superdisintegrants, flavorings, antioxidants, preservatives, thickeners, and also mixtures thereof. One or more of the ingredients described above may be present in one particle of the powder mixture. A method of obtaining a combined first powder mixture (symbiotic) includes a dry complex preparation of bifido and lactobacilli homogeneous, loose bran-shaped or flour powder sorbed on natural plant carriers. (12 parts by weight of carrier and one part by volume of a mixture of concentrated dried cultures), while to obtain a bacterial concentrate, liquid cultures of a consortium of bifido and lactobacilli (Bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LH-1) with a titer of 10 ⁸ -10 ¹⁰ CFU / g of adsorbed on a carrier in a ratio of 1: 1: 12 is concentrated by filtration or centrifugation to obtain a suspension containing 5 billion bacteria in I ml (according to the optical GISK turbidity standard) and mixed in equal volumes. Flour or bran is used as a carrier at the rate of 12 parts of a carrier for I part of a mixture of concentrated cultures, then contact-sorption drying of biomass is carried out, then the resulting dry powder mass is mixed with lactulose in a mixer for 8-10 minutes.

A method of obtaining a combined second powder mixture is to mix ivermectin and praziquantel with a microcrystalline cellulose filler in a quick mixer for 8-10 minutes, while the components of the first and second powder mixtures are taken in the following ratio of mass components. %:

ivermectin 0.20 praziquantel 5.00 consortium of bifido and lactobacilli (Bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LH-1) with a titer of 10 ⁸ -10 ¹⁰ CFU / g sorbed on the carrier in a ratio of 1: 1: 12 34.00 lactulose 20.00 microcrystalline cellulose MCC 34.00

Before use, one tablet, designed for 10 kg of animal’s live weight, is diluted in two ml of water for subsequent dissolution and formation of a suspension, which is forcedly injected into the root of the tongue using a syringe dispenser.

The effectiveness of the drug is determined by the results of fecal samples from 10 lambs and 10 ewes 10 days after deworming.

10 days after the administration of the drug, helminth eggs were found in fecal samples in 8 out of 10 animals. Thus, the drug at a dose of 1 tablet / 10 kg of animal weight showed an effectiveness of only 20%, and Example 1 showed weak anthelmintic efficacy, due to the low dose of the components responsible for the anthelmintic effect of the drug.

Example 2. A method of manufacturing a combined anthelmintic tablet with a symbiotic for the treatment of small cattle is carried out analogously to example 1, but the components of the first and second powder mixtures are taken in the following ratio of mass components. %:

ivermectin 0.27 praziquantel 7.00 consortium of bifido and lactobacilli (Bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LH-1) with a titer of 10 ⁸ -10 ¹⁰ CFU / g sorbed on the carrier in a ratio of 1: 1: 12 35.00 lactulose 21.00 microcrystalline cellulose MCC 35.00

The effectiveness of the drug is determined by the results of studies of fecal samples from 20 lambs spontaneously infected with strongilates of the gastrointestinal tract and lungs, nematodiras, trichocephalus, strongyloids, dictiocaul, moniesia. It was found that the drug at a dose of 1 tablet / 10 kg of animal weight 10 days after deworming showed 100% effectiveness against major helminthiases of the gastrointestinal tract of animals (strongilates, nematodes, trichocephalus, strongyloids, dictiocaula and moniesia).

Example 3. A method of manufacturing a combined anthelmintic tablet with a symbiotic for the treatment of small cattle is carried out analogously to example 1, but the components of the first and second powder mixtures are taken in the following ratio of mass components. %:

ivermectin 0.28 praziquantel 7.14 consortium of bifido and lactobacilli (Bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LH-1) with a titer of 10 ⁸ -10 ¹⁰ CFU / g sorbed on the carrier in a ratio of 1: 1: 12 35.71 lactulose 21.43 microcrystalline cellulose MCC 35.44

The effectiveness of the drug is also determined by the results of studies of fecal samples from 20 lambs spontaneously infected with strongilates of the gastrointestinal tract and lungs, nematodiras, trichocephalus, strongyloids, dictiocaul, moniesia. It was found that the drug at a dose of 1 tablet / 10 kg of animal weight 10 days after deworming showed 100% effectiveness against major helminthiases of the gastrointestinal tract of animals (strongilates, nematodes, trichocephalus, strongyloids, dictiocaula and moniesia).

Example 4. A method of manufacturing a combined anthelmintic tablet with a symbiotic for the treatment of small cattle is carried out analogously to example 1, but the components of the first and second powder mixtures are taken in the following ratio of components, mass. %:

ivermectin 0.30 praziquantel 8.00 consortium of bifido and lactobacilli (Bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LH-1) with a titer of 10 ⁸ -10 ¹⁰ CFU / g sorbed on the carrier in a ratio of 1: 1: 12 35.9 lactulose 23.00 microcrystalline cellulose MCC 37.30

The effectiveness of the drug is determined by the results of fecal samples from 10 lambs and 10 ewes 10 days after deworming.

10 days after drug administration, helminth eggs were not found in animals in all samples. The drug in animals at a dose of 1 tablet / 10 kg of body weight showed 100% effectiveness against helminths of the gastrointestinal tract and lungs. Thus, example 4 in terms of the effectiveness of anthelmintic action does not differ from examples 2 and 3, but in example 4, there is an overspending of anthelmintic substances, which leads to a rise in the cost of the drug.

Thus, the most optimal are examples 2 and 3 of the production method of a combined anthelmintic tablet with a symbiotic for the treatment of small cattle.

Examples of test results of anthelmintic tablets in animals.

Example 5. Anthelmintic effect. The claimed drug in the form of tablets is intended for the treatment of cestodoses, nematodes and mixtinvasions of ruminants.

The finished preparation in tablet form is given to animals individually orally once at the rate of 1 tablet per 10 kg of body weight. A special diet and the use of laxatives to animals before deworming is not required.

Evaluation of the therapeutic efficacy of the drug is carried out with mixed infections of lambs.

Thirty lambs aged 4-5 months of the North Caucasian breed, spontaneously invaded by moniesiosis, and strictilatoses of the gastrointestinal tract are taken into the experiment. The animals were divided into three groups of 10 animals each. The drug, combined two-layer anthelmintic tablets with a symbiotic (KDVATSS) is given to the lambs of the first experimental group at the rate of 1 tablet per 10 kg of animal weight. The animals of the second experimental group are fed Monizen preparation at the rate of 1 ml of suspension per 10 kg of body weight. The control group is not subjected to treatment. Treated animals are released into the flock, where they are kept under identical conditions as the untreated sheep.

The effectiveness of the treatments is determined by the results of studies of fecal samples from 30 lambs before giving the drug and 10 days after deworming.

In all feces samples, before giving the medicine (05/01/2016), strongilate eggs were found in an amount of 27 to 115 ind. in three drops, in 9 samples single eggs nematodir, in 8 samples - moniesia eggs.

10 days after administration of the drug in the first experimental group of animals in all samples of helminth eggs were not found. Thus, the drug at a dose of 1 tablet / 10 kg of animal weight showed 100% efficacy against moniesiosis, strictilatoses of the gastrointestinal tract and lungs. In the second group of lambs treated with monizen, no samples of feces of eggs and helminth larvae were found, which indicates 100% efficiency. In the control group, a high degree of invasion of animals remained.

Example 6. Immunostimulating activity and effect on the liver of a combined anthelmintic pill with a symbiotic.

The finished drug in the form of a suspension is given to animals individually, orally, once at the rate of 1 tablet per 10 kg of body weight. A special diet and the use of laxatives to animals before deworming is not required.

30 lambs aged 4-5 months of the North Caucasian breed, spontaneously infested with moniesiosis, strictilatoses of the gastrointestinal tract and lungs, are also taken into the experiment. Animals are divided into three groups of 10 animals each. The drug with a symbiotic (KDVATSS) in the form of a suspension is given orally to the lambs of the first experimental group at the rate of 1 ml per 10 kg of animal weight. The animals of the second experimental group are fed Monizen preparation at the rate of 1 ml of suspension per 10 kg of body weight. The control group was not treated.

Treated animals are released into the flock, where they are kept under identical conditions as the untreated sheep. To study the effect of anthelmintic drugs on the body of lambs, blood samples were taken from the jugular vein for studies on the 10th day after the drugs were injected into the VACUETTE EDTA vacutainers.

Biochemical blood tests are carried out on the basis of the laboratory of infectious, non-communicable diseases and parasitic diseases of the Federal State Research Institution VNIIOK on the SPEKOL 211 analyzer using test reagents from Lahema and Olveks Diagnosticum LLC.

In the blood serum determine the level of total bilirubin, albumin, the activity of the enzyme aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, as well as the immunological reactivity of the body of lambs (T and B lymphocytes, lysozyme, phagocytic and bactericidal activity). The results are presented in the table.

Analyzing the immunological parameters presented in the table, it should be noted that in the group where combined two-layer anthelmintic tablets with a symbiotic (KDVATSS) are used, on the 10th day there is an increase in the number of lymphocytes by 14.73%, compared with the group of animals treated with monizen and in comparison with the control group by 32.43%, respectively.

By the 10th day in the control group of animals, the number of rosette-forming B-lymphocytes was 15.40 ± 1.03%, which indicates the adverse effect of strongilates of the gastrointestinal tract on the provision of humoral immunity (table). There is an increase in the level of B-lymphocytes in the first experimental group by 9.67% compared with the second group and by 17.69% compared with the control. On the 10th day after the use of drugs in the first experimental group receiving combined two-layer anthelmintic tablets with a symbiotic (KDVATSS), in relation to the second experimental group of animals, an increase in bactericidal (BASK) and lysozyme (LASK) activity of blood serum is observed by 43.62% and 32.71%, respectively. In relation to the control, the indicators of bactericidal (BASK) and lysozyme (LASK) activity of blood serum of the first experimental group increased by 67.17 and 64.01%, respectively. The phagocytic activity of neutrophils (FASK) in relation to the group of animals receiving monizen increased by 36.61, and to the control group by 65.10%, respectively.

A decrease in the level of total bilirubin was observed on the 10th day in animals of the first experimental group. Its content in blood serum decreased, compared to the second experimental group, by 15.50% and by 63.18% with the control group, respectively.

On the 10th day after deworming, the content of albumin in the blood serum of sheep not subjected to medical manipulations was low and was at the level of 16.9 ± 4.9 g / l, which indicates the effect of helminths on the liver. On the contrary, albumin in the blood serum of sheep from experimental groups was at a high level. This process is most pronounced in the blood serum of animals treated with combined two-layer anthelmintic tablets with a symbiotic (KDVATSS) in comparison with the Monizen group received at 24.9% and in comparison with the control group at 49.32%

After treatment of the animals on the 10th day in the control group that did not receive treatment, a high level of alkaline phosphatase level of 192.35 ± 0.7 U / L was recorded in blood serum. However, in the experimental groups, the restoration of the alkaline phosphatase enzyme content to physiological values is recorded. In the first experimental group of animals, this indicator on the 10th day of the experiment decreased by 4.01% compared with the indicators of the second experimental group and by 23.9% in comparison with the control group, respectively.

The activity of the enzymes AlAT and AsAT in the first experimental group of animals was lower by 52.54% and 6.97% compared with the second experimental group and compared with the control group by 45.15% and 32.01%, respectively.

Thus, based on the data obtained, it can be concluded that the use of combined two-layer anthelmintic tablets with a symbiotic (KDVATSS) favorably affects the immune status and general resistance of animals. There is a positive effect of drugs on the activity of liver enzymes, which reflect the favorable functional state of hepatocytes, which in turn ensures an active metabolic status of animals, and eliminates the adverse effect from the use of anthelmintic drugs on the animal's body.

The invention in comparison with the prototype and other known technical solutions has the following advantages:

- high anthelmintic activity;

- has non-specific hepatoprotective, immunostimulating and adaptogenic properties;

- contributes to the intensification of treatment and prevention of a number of helminthic invasions, accompanied by a decrease in the immunobiological properties of the body and a decrease in the reparative properties of the liver.

Claims (2)

A method of manufacturing a combined anthelmintic tablet with a symbiotic for treating small cattle comprising a first and second layer, comprising the steps of: adding a first powder mixture to a mold plate, said first powder mixture containing a pharmaceutically active substance and a binder, adding a second powder mixture onto said mold plate, said second powder mixture containing a binder, and the composition of said second powder mixture different from comp This indicated first powder mixture is pressed, the first powder mixture and the second powder mixture are pressed on the indicated plate of the mold to form a tablet form and the specified tablet form is subjected to radio frequency radiation for a period of time sufficient to activate the specified binder inside the specified tablet form to fuse the specified tablet forms in said tablet so that the density of said tablet is less than about 0.8 g / cm ³ , distinguishing In order to obtain the first powder mixture, a bacterial concentrate is prepared, including a consortium of bifido and lactobacilli Bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LH-1 with a titer of 10 ⁸ -10 ¹⁰ CFU / g sorbed on a carrier in a ratio of 1: 1: 12, which concentrated by filtration or centrifugation to obtain a suspension containing 5 billion bacteria in 1 ml, followed by mixing them in equal volumes, moreover, flour or bran are used as a carrier at the rate of 12 parts of a carrier for I part of a mixture of concentrated cultures, thoroughly sorption drying of biomass, and then the resulting dry powder mass is mixed with lactulose, and ivermectin, praziquantel and at least one pharmaceutically acceptable excipient, microcrystalline cellulose MCC, are used to obtain a second powder mixture, then ivermectin, praziquantel and dry in the following ratio of components wt.%: ivermectin 0.27-0.28 praziquantel from total tablet forms 7.00-7.14 consortium of bifido and lactobacilli Bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LH-1 with a titer of 10 ⁸ -10 ¹⁰ CFU / g sorbed on the carrier in a ratio of 1: 1: 12 35.00-35.71 lactulose 21.00-21.43 microcrystalline cellulose MCC 35.00-35.44

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