WO2013019145A2 - Biologically active product for use in veterinary medicine and animal husbandry, method for producing same and methods for enhancing viability, stimulating growth, stimulating immune function and enhancing the general non-specific resistance of livestock - Google Patents

Abstract

The invention relates to the field of veterinary medicine and animal husbandry and, more specifically, to a method for producing a biologically active product of natural origin for use in veterinary science and animal husbandry, which exhibits an immune-stimulating, immune-modulating and growth-stimulating effect as well as enhancing general non-specific resistance and exhibiting an adaptogenic effect and contains seeds or sprouts of plants of the grass family, fertilized fish roe, insect larvae and fertilized bird eggs in the early stages of development. The invention further relates to a biologically active product produced using the aforesaid method, and to methods for enhancing viability and stimulating growth in young livestock (a) and stimulating immune function and enhancing general non-specific resistance in livestock (b), which involve the intramuscular or subcutaneous administration of the biologically active product according to the invention to said livestock (in a carrier acceptable for veterinary use). The biologically active product according to the invention exhibits a pronounced growth-stimulating and immune-stimulating effect, is inexpensive to produce and does not contain toxic (carcinogenic) solvents.

Description

 Biologically active product for use in veterinary medicine and animal husbandry, a method for its production and methods for increasing survival, growth stimulation, immunostimulation and increasing the general nonspecific resistance of an organism

 farm animals

DESCRIPTION

The invention relates to the field of veterinary medicine, animal husbandry and zootechnology, namely, to a biologically active product based on components of natural origin, intended for use in veterinary medicine and animal husbandry, having immunostimulating, immunomodulating, growth-promoting, stimulating the general nonspecific resistance of the body action, and also to a method for preparing said biologically active product and to methods for increasing survival and growth stimulation in young rural farm animals and immunostimulation and enhance overall

nonspecific resistance of the organism of farm animals, including intramuscular or subcutaneous administration of a biologically active product in accordance with the invention to said animals.

Currently, due to a number of objective and subjective reasons

(insufficient protein feeding of farm animals, the effects of various harmful chemicals (in particular pesticides, often

contained in animal feed), increased radiation background, etc.), immunodeficiency states and growth disorders of animals, especially young animals, very often occur.

 To increase the body's defenses, various

immunostimulants; the use of such drugs in veterinary medicine allows increasing the body's defenses of animals, which, in turn, leads to an increase in the immune response during vaccinations (vaccines are more effective) and an increase in the activity of antibiotics and other antimicrobial agents. The prior art method of complex activation of the protective forces of the animal’s body, including intramuscular or subcutaneous administration of a biogenic stimulator containing 30 g of tissue emulsion from the bodies of the larvae of bestial flies (wolfarth fly, green sheep’s (meat, carrion) fly, spring blue fly), 10 , 0 g of natural bee honey in May, 59.8 g of 0.9% sodium chloride solution and 0.2 g of formalin (RF patent U 2400242 C1 “Method for the integrated activation of the protective systems of the body”, patent start date 15.07.20 09 (application RU 2009127292/15), published on 09/27/2010 (patent holder and inventor - Moiseev OI (RU)).

The specified tool is administered to a sick animal intramuscularly or subcutaneously at a rate of 0.02-0.05 ml / kg body weight, preferably in the ^L L portion of the dose to the left and right of the spinal column in the dorsal muscles of the lower back, or subcutaneously on the right and left sides of the neck or 1/5 of the dose in six places around the focus of the pathology, or combined 3/8 of the dose in the muscles of the lower back to the right and left of the spinal column and 1/3 of the dose in six places around the pathological focus, once or several times with an interval of 5-7 days.

 As a preservative, this agent contains formalin - an aqueous solution of formaldehyde, for which it has been repeatedly shown in the literature

carcinogenicity, mutagenicity and cytotoxicity - both in relation to humans and in relation to animals (see, for example, Lewis V.V. (1981)); This circumstance makes it difficult to use the composition according to RU 2400242 C1 in veterinary medicine and animal husbandry.

 In the patent of the Russian Federation RU 2264221 C1 "Method for the preparation of a complex immune modulator", publ. November 20, 2005 (inventors - Pogodaev V.A. (RU), Morenko E.A.

(RU), Kits E.A. (RU), patent holder - Federal State

educational institution of higher professional education

 "Stavropol State Agrarian University" (RU)) disclosed a method of preparing an immune modulator, comprising cooling selected fertilized uninfected eggs at a temperature of 2-4 ° C for up to 7 days,

homogenization, dilution with saline egg mass,

bactericidal treatment, preservation with phenol solution to its 0.3%

concentration, followed by filtration of the target product, characterized in that the egg mass is diluted with saline in a ratio of 1: 5, then heat treatment is carried out in a water bath at a temperature of 70-8C for 1 hour and before preservation, the target product is cooled in a bactericidal chamber under an ultraviolet lamp for 30-40 minutes.

Although this drug, obtained by the method in accordance with RU 2264221 C1, can indeed be used in veterinary medicine and animal husbandry as an immunomodulating agent, the phenol contained in it as a preservative, as has been repeatedly shown in the literature, also has a bright

pronounced carcinogenic and mutagenic properties, which makes it difficult

the use of this drug in veterinary practice to the same extent as in the case of the drug according to patent RU 2400242 C1.

 This disadvantage (the presence in the finished preparation of phenol or formalin, known for their carcinogenicity, mutagenicity and cytotoxicity) is inherent in the technical solution disclosed in patent RU 2345523 C2 “Method for the integrated activation of the protective devices of the animal’s body” (inventors - V. Pogodaev ( RU), Morenko E.A. (RU), Ponomarev O.V. (RU), Moiseev O.N. (RU),

Klimenko A.I. (RU), Ovcharov A.P. (RU), patent holder - State Scientific Institution of the Russian Agricultural Academy, North Caucasian Zonal Scientific Research Veterinary Institute (GNU SKZNIVI) (RU)), in accordance with which an animal is given a biogenic stimulator, and a drug containing, g or mass. %: tissue emulsion from the bodies of drones of bee brood - 20.0 g (or 20 wt.%), fresh bee honey - natural 20.0 g (or 20 wt.%), 0.9% sodium chloride solution - 59.7 g (or 59.7 wt.%), as well as formalin or phenol (as

preservative) - 0.3 g (0.3 wt.%); said agent is administered subcutaneously or

intramuscularly to the right and left of the spinal column into the dorsal muscles, to the right and left of the neck, thigh or other parts of the body, 1 2-part of the dose at the rate of 0.05-0.08 ml / kg of body weight.

 Also known (RF patent RU 2258522 C1, publ. 08/20/2005, the inventors -

Lutsuk S.N. (RU), Belyaev V.A. (RU), Salushcheva M.S. (RU), Ruchiy O.S. (RU), Safonovskaya E.V.

(RU), patent holder — Federal State Educational

institution of higher professional education Stavropol State Agrarian University (RU)) a method for preparing a preparation for stimulating the organism of animals from drones larvae, comprising collecting drones larvae, homogenizing them with the addition of a stabilizing medium, characterized in that drones are frozen before homogenization at a temperature of -4 ° С - 5 ° С for 12-14 hours, then thawed for 3-5 minutes to + 18 ° C, while a stabilizing medium using a 5% glucose solution in a ratio of 1:10, with the addition of a 5% solution of chloroform or 2% salicylic acid, followed by minutes sublimation, the sublimation is carried out in a vacuum chamber at a temperature of heating the shelves and + 30 ° C - + 45 ° C, wherein when the temperature of the drug + 20 ° C - + 22 ° C shelf temperature was lowered to + 25 ° C and produce

drying for 22-24 hours.

 The preparation obtained in accordance with RU 2258522 C1 may contain residual amounts of solvent — chloroform, which, as has been repeatedly shown in the literature, also has carcinogenic, mutagenic, embryotoxic, and teratogenic properties, and can also lead to miscarriages in pregnant female domestic (agricultural ) animals; in addition, the preparation obtained by the method in accordance with RU 2258522 C1 is characterized by a limited spectrum of application and low biological activity.

 Known from the prior art (EP 0818202 A1 "DNA-RNA hybrid and a DNA preparation, methods of obtaining said hybrid and preparation from sturgeon milt, and a pharmaceutical compound based on said DNA-RNA hybrid", inventors ANOSOVA Lidia

 Grigorievna (RU), BEZJULEV Vyacheslav Vladimirovich (RU), NESTEROVA Evgenia Ivanovna

(RU), the applicant - NAUCHNO-PROIZVODSTVENNOE PREDPRIYATIE "FARMEK" (RU), as well as the corresponding patents of the Russian Federation (RU 2108796 C1 and RU 2108797 CI)) a method for producing a hybrid DNA-RNA preparation having immunotropic and antiviral activity by processing the original cellular material, characterized in that the cellular material (milk of sturgeon fish) is homogenized, treated with detergent, precipitated protein, purified from impurities, incubated for 20-90 minutes at a pressure of 1.5-2 atmospheres, a temperature of + 105 ° C - + 115 ° C and a pH of 8.5-9.0, depressurize and incubate the product at a temperature of + 55 ° C - + 60 ° C and at pH 5, 5-7.5 for 1-4 hours, followed by precipitation and washing with alcohol (EP 0818202 A1, RU

2108796 C1), as well as a method for producing a hybrid DNA-RNA preparation having immunotropic and antiviral activity, by processing the source of cellular material, characterized in that the raw materials (milk of sturgeon) are homogenized, the cell material is incubated, conduct detergent

deproteinization, salt denaturation of the released proteins, then ultrasound treatment at a temperature of + 10 ° С - + 18 ° С in an air atmosphere in the presence of a one-, two- or three-component system selected from the group of metal salts, oxidizing agents, carbohydrates, reducing agents and metal salts with variable valency, followed by purification and isolation of the target product having a molecular weight of 300-500 kDa, RNA content from 3 to 5%, protein from 0.7 to 1.5%, metals of variable valency not more than 0.001% with a nitrogen / phosphorus from 1.0 to 1.5, (EP 0818202 A1, RU 2108797 C1).

 EP 0 818 202 A1 also discloses a pharmaceutical composition containing from 0.5% to 5% of a product (preparation) obtained by the above method together with a pharmaceutically acceptable solvent (up to 100%).

 Although for the drug in accordance with EP 0818202 A1, RU 2108796 C1 and RU 2108797 C1, in vitro and in vivo experiments show the presence of antiviral activity (including activity against herpes virus, influenza virus, adenoviruses and HIV), as well as the presence of cytotoxic and immunotropic activity, however, information related to the possibility of using this drug in

farm animals, in EP 0818202 A1 and in the corresponding patents of the Russian Federation RU 2108796 C1 and RU 2108797 C1 are absent.

 Also known from the prior art is a method for producing a food, or pharmaceutical, or balneological, or cosmetic formulation (patent RU 2204381 C2 “A method for producing a food, or pharmaceutical, or balneological, or

cosmetic formulations ", the date of commencement of the patent 05/11/2000 (application RU

 2000111795/14), publ. 04/12/2006 (inventors - Decina A.N. (RU), Sirotkina

T.B. (RU), patent holder - Decina A.N. (RU))), including separate

preparation of a concentrate of nutritious and biologically active components and a base, dilution of a concentrate with a base by mixing the indicated parts of the formulations with each other to prepare their finished forms, packaging, storage and subsequent use of the finished formulations, characterized in that the concentrate of nutrient and biologically active components containing drone homogenate brood, or sperm homogenate, and / or caviar of gray sea urchins, or ascidia caviar, and / or ascidium sperm, or milk and / or fish roe, or rooster sperm, or homogenate of bird embryos and / or components of bird eggs, or whole colostrum mammals, or homogenate of scallop gonad, or homogenate of male and / or female mussel gonads, or culture medium removed from human and / or animal leukocyte cell culture, undergoing logarithmic growth and containing growth factors and metabolic products of these leukocyte cells, Lebanon total osmotic activity not less than 2000 mOsm / L by introducing an osmotic activity regulators; the content of each component in the specified concentrate is a multiple of its content in the final prescription form when it is obtained by diluting the concentrate with a base; after preparation of the base and concentrate of nutrient and biologically active components, these parts of the product are packaged and stored separately: the base is at room temperature, and the concentrate is at room temperature or in a refrigerator, and when preparing the finished formulations, the concentrate of nutrient and biologically active substances is mixed with the base of the product immediately before use.

 Although in accordance with private forms of embodiment of the invention according to patent RU

2204381 C2, in particular, a concentrate can be obtained for the preparation of

pharmaceutical immunostimulating agents for oral administration

(see RU 2204381 C2, description, page 6, Example 7) and pharmaceutical

immunostimulating agent for oral use (see RU 2204381 C2, description, page 7, Example 18), however, the presence of an immunostimulating and

growth-promoting activity in a pharmaceutical preparation that can be obtained by the method proposed in accordance with RU 2204381 C2 (see RU 2204381 C2, description, p. 7, Example 18), in the patent RU 2204381 C2 is not confirmed.

 From Romanian patent RO 118115 In "Biologically active substance, process for preparing the same, utilization of the biologically active substance" (patent start date

06.06.2000, publ. 02/28/2003, inventor and patent holder - CIUHRII MIRCEA

(RO)) (in the amount of the abstract) is known biologically active substance (biologically active product) for the treatment of infectious diseases of the liver, containing 4,84-

7.97 mass. % glutamine; 4.10-8.45 mass. % phenylalanine; 3.76-5.23 mass. % asparagine;

2.04-4.44 mass. % lysine; 1.50-2.79 mass. % threonine; 2.72-3.10 mass. % proline; 1.65- 3.10 mass. % alanine; 1.80-2.54 mass. % valine; 1.37-2.59 mass. % isoleucine; 1.41-3.04 mass. % tyrosine; 1.91-3.61 mass. % arginine; 0.83-1.17 mass. % histidine.

RO 118 115 B also discloses a method for producing a biologically active product, including collecting eggs and pupae of unpaired silkworms (Latin name (lat.) Lymantria dispar), Colorado potato beetle larvae (lat. Leptinotarsa decemlineata) and adult western May beetle (lat. Melolontha melolontha ), their sterilization, grinding in an electric mill at a speed of 2500-5000 rpm (until a homogeneous homogeneous mass of light gray color is obtained), filtering the specified mass through a woven filter with a hole diameter (pore) of 200 to 250 microns, isolating residues (f iltrate?), filtration using a vacuum filter (up to obtaining a light gray suspension), lyophilization and spraying to obtain a lyophilisate powder, and the use of the specified biologically active substance (biologically active product) for the preparation of a medicinal product (medication) for the treatment of infectious liver disease.

The biologically active product in accordance with RO 118115 B is intended only for the treatment of infectious diseases of the liver; the possibility of using this product as an immunostimulating, immunomodulating and

a growth-promoting veterinary agent is not indicated.

 RF patent RU 2157232 C1 “The drug and method for its preparation” (publ. 10.10.2000, inventors and patent holders - F. Luknitsky (RU), Potapov AM (RU), Valov G.Yu. (RU)) discloses the drug having immunostimulating and adaptogenic action; the specified preparation contains a water-alcohol extract of the active principle of plant origin (active components of wheat germ), with the ratio of ingredients in the specified preparation, wt.%:

ethyl alcohol - 30-40;

Water - 58 - 68;

tocopherols from wheat germ - 0.0003 - 0.001;

vitamin B ₆ - 0.005-0.01;

other hydrated components from wheat germ - the rest.

Patent RU 2157232 C1 also discloses a method for producing said

immunostimulating and adaptogenic preparation based on wheat germ, including treatment of the germ with a solvent (30-50% aqueous solution ethyl alcohol) at room temperature for at least 20 minutes, separating the extract (by decantation, filtration or a combination of decantation and filtration), heat treatment (heating the extract at a temperature of + 60 ° C - + 70 ° C for at least 40 minutes ), isolation of the active principle and purification of the final product (filtration through activated carbon).

The final product obtained by the method in accordance with patent RU 2157232 C1 contains large amounts of ethyl alcohol, which makes its course veterinary use undesirable for the treatment (treatment) of large

livestock; in addition, heating to a temperature of + 60 ° C - + 70 ° C for at least 40 minutes can lead to the destruction of a significant part of the biologically active substances contained in the wheat germ.

It also seems useful to supplement the useful properties of a complex of biologically active substances from wheat germ contained in the preparation according to patent RU 2157232 C1, the useful properties of biologically active substances contained in other types of plants and animals.

 In the patent of the Russian Federation RU 2395289 C1 “Method for the preparation of a biogenic stimulator from larvae of drone brood of bees”, the patent commencement date is 24.11.2008 (application RU

 2008146273/15), publ. 07/27/2010, inventors - Pogodaev Vladimir Anikeevich

(RU), Klimenko Alexander Ivanovich (RU), Zubenko Alexander Alexandrovich (RU),

Fetisov Leonid Nikolaevich (RU), Klimenko Vladimir Alexandrovich (RU), Pogodaev

Alexey Vladimirovich (RU), patent holder - State Scientific Institution

North Caucasian Zonal Research Veterinary Institute

Russian Academy of Agricultural Sciences (RU)) proposed a method

preparation of a biogenic stimulator, including 50% of the biologically active mass from drones larvae, 49.7% sodium chloride solution and 0.3% preservative, characterized in that for the preparation of the preparation, cells with live healthy drone brood aged 18-22 days are kept in the refrigerator at at a temperature of 3-4 ° C for 5-6 days, then the brood honeycombs are opened and drones of the same size, light gray in color, are selected, after which the drones are crushed in a sterile laboratory mill, diluted with a sterile solution of sodium chloride Ia with a concentration of 0.9% in the ratio 1: 1 and autoclaved at

temperature inside the boiler + 120 ° С and steam pressure in the jacket 1.5 atmospheres for 1 h, then the mass is filtered through 2 layers of gauze in a sterile volumetric dish, adjusted with a sterile solution of sodium chloride with a concentration of 0.9% to

of the original volume, add a preservative (phenol), pour, subject to the rules of asepsis and antiseptics, into prepared sterile bottles and seal them tightly, autoclave at 120 ° С and a vapor pressure in a jacket of 1.5 atmospheres for 20 minutes.

 The disadvantage of the method disclosed in RU 2395289 C1 is the need for a long (within 1 hour) autoclaving of the drug at high temperature (+ 120 ° C) and a pressure 1.5 times higher than atmospheric; specified conditions

Autoclaving leads to almost complete degradation of biologically active substances in the preparation.

 A similar drawback (the need for prolonged heating and aging of the product (preparation) at high temperatures close to + 100 ° C, leading to the degradation of biologically active substances in the preparation) is also characteristic of the method for producing a preparation that increases the resistance of animals disclosed in RF patent RU 2264222 C1 "A method of obtaining a drug to increase the resistance of the animal organism" (patent start date 12/08/2003, application RU

2003135683/15, authors of the invention - Evglevsky A. A. (RU), Lebedev A.F. (RU)

Evglevskaya E.P. (RU), Kolomiytsev SM. (RU), Pankova SJ. (RU), Ryzhkova G.F. (RU), Rusakova N.M. (RU)).

 In the patent of the Russian Federation RU 2414919 C1 "Method of preparation of the drug to increase the General and specific resistance of the animal organism" (the date of the patent

07/06/2009, application RU 2009125832/15, inventors - Valery Belyaev

 Anatolyevich (RU), Safonovskaya Evgenia Vyacheslavovna (RU), Valeria Pereverzeva

Nikolaevna (RU), patent holder - Federal State Educational Establishment of Higher Professional Education "Stavropolsky

State Agrarian University "(RU)", proposed as the closest analogue of the present invention, a method for preparing a preparation for increasing the general and specific resistance of an animal organism is proposed, wherein said preparation is obtained from drones larvae from 5 to 14 days old.

The method proposed in accordance with RU 2414919 C1 includes collecting drones larvae from 5 to 14 days old, freezing them for 3-5 minutes at temperature -4 - -5 ° C for 12-14 hours, followed by thawing to + 18 ° C and homogenization, followed by the addition of a stabilizing medium,

acetylsalicylic acid and sublimation (moreover, sublimation is carried out in a vacuum chamber at a temperature of shelf heating to + 30 ° С - + 45 ° С, while when the temperature reaches + 20 ° С - + 22 ° С, the temperature of the shelves is reduced to + 25 ° С ) and drying for 22-24 hours, characterized in that diacetophenonyl selenide is used as the organo-selenium compound, and a drying medium is used as a stabilizing medium — a sucrose-gelatin mixture comprising 10% sucrose and 5% gelatin in a ratio of homogenate and drying medium 1:10 , etc drones are taken from 5 to 14 days old, homogenization is carried out for 3-5 minutes, and diacetophenonyl selenide is added after homogenization in an amount of 3.5-4 mg per 100 ml of homogenate, then homogenate and acetylsalicylic acid in an amount of 0.2% to the volume, knead for 2-3 minutes, filter through 4-5 layers of sterile gauze, place in a thermostat at a temperature of 50-55 ° C for 35-40 minutes, and after a set time, the drug is transferred to another thermostat at 37 ° C for 8 ocloc'k. The specified cycle is repeated three times, followed by cooling to room temperature and the addition of sterile drying medium under sterile conditions, by packing, freezing at -50 ° C and sublimation.

The specified method, although devoid of the disadvantages inherent in the methods of obtaining

preparations in accordance with RU 2395289 CI, RU 2264222 C1 and RU 2157232 C1, however, is characterized by a very complex and multi-stage technology for producing the drug. In this regard, the relevance of creating an immunostimulating,

growth-promoting, adaptogenic and increasing the general nonspecific resistance of the organism of a veterinary preparation that does not contain toxic and / or carcinogenic substances and is relatively simple and inexpensive to obtain, is preserved.

 Brief Description of the Drawings:

 FIG. 1: Live weight of piglets (from birth to 6 months) when using the drug (in comparison with the control group)

FIG. 2: Preservation (survival) of piglets when using the drug (%, compared with the control group) FIG. 3: Live weight of calves from birth to up to 6 months when using the drug (in comparison with the control group)

 FIG. 4: Preservation (survival) of calves when using the drug,% (compared with the control group)

 FIG. 5: Indicators of immunity (immunogram) of animals of the experimental and control groups.

 The invention:

 In the framework of the present invention, the authors were able to develop a biologically active product of natural origin for use in veterinary medicine and animal husbandry, with immunostimulating, immunomodulating, growth-promoting, increasing the overall nonspecific resistance of the organism and adaptogenic effect, much easier to obtain in comparison with drugs known from the prior art, while devoid of the disadvantages inherent in the known prior art solutions.

 The biologically active product in accordance with the invention contains a full range of biologically active substances from animal and vegetable tissues

origin, possessing immunostimulating, immunomodulating, increasing the general nonspecific resistance of the organism and adaptogenic effect, increases the productivity of animals (while maintaining optimal indicators of protein, mineral and lipid metabolism), allows animals to better adapt to the action of stress factors, does not accumulate in the organs and tissues of animals (i.e. no cumulative effect), has a natural origin (which provides safety benefits

use of this drug, in comparison with synthetic

immunostimulants and growth stimulants used in veterinary medicine and animal husbandry), and can be successfully used in all types of farm animals of various sex and age groups - to increase survival and growth of young animals, to smooth out complications after vaccination, for the complex treatment of infectious and protozoal diseases in farm animals, and .tp

According to the claimed invention, seeds or seedlings of plants of the cereal family (preferably seedlings aged 5-7 days of plants such as rye (Secale cereale), seed oats (Avea sativa), ordinary barley (Hordeum vulgare), common wheat (Triticum vulgare) and corn (Zea mays)), fertilized fish eggs (preferably fish that are allowed to

industrial capture and caviar which is not poisonous, the most

preferably carp (Cyprinus carpio), carp (Cyprinus carpio), silver carp

(Hypophthalmichthys molitrix), rudd (Scardinius erythrophthalmus) and trout (Salmo species)), insect larvae (preferably flies (Muscidae), coconut moths (Lasiocampidae), mosquito-withers (Chironomidae), tubule makers (Tubificidaidae, ) and bee (Apidae)) and fertilized bird eggs

(preferably birds of the chicken order (Galliformes), birds of the order of ducks (Anatidae) or birds of the order of Anseriformes) are incubated in the early stages of development, followed by cooling (preferably, cooling is carried out at a temperature of + 7 ^ С - +9 ⁵ С , for 4-12 hours), homogenization, dilution of the homogenate with a 0.9% sodium chloride solution in a ratio of 1: 2-1: 5, pasteurization, filtration, the addition of a preservative, the addition of a cryoprotectant, bottling, lyophilization and sterile capping.

Preferably, within the framework of the present invention, pasteurization is carried out in a water bath at a temperature of +56 ^e C to +70 ^d C for 1.5-3 hours; preferably, 1-5% mannitol, or 1-5% sucrose, or 1-5% glucose, or 1-5% lactose, or 1-5% trehalose is used as the cryoprotectant in the most preferred (however, not limiting the scope of claims in accordance with the present invention) embodiment, the composition of the biologically active product contains:

 - seeds or seedlings of plants of the cereal family - 20-35 mass. %;

 - fertilized fish eggs - 15-20 mass. %;

 - insect larvae - 15-20 mass. %;

 - fertilized eggs of birds - 20-25 mass. %;

 - a pharmaceutically acceptable carrier - the rest (up to 100%).

Immediately before use, the drug is diluted with 0.9% NaCI solution or sterile pyrogen-free distilled water for injection.

 Biologically active product obtained in accordance with this

the invention may additionally contain acceptable in veterinary medicine

fillers, excipients, preservatives (in particular, as a preservative within of the present invention can be used nipagin in the form of 0.01-0D% solution) and other auxiliary components, and is suitable for intramuscular or

subcutaneous administration to farm animals in need.

The following examples reflect particular embodiments of the invention and serve only to illustrate the claimed invention, and not to limit the scope of claims.

 Example 1. Obtaining a biologically active product

in accordance with the invention.

 (1) Seeds and seedlings (5-7 days old) of seed rye (Latin Secale cereale), or seed oats (Latin Avea sativa), or ordinary barley (Latin Hordeum vulgare), or ordinary wheat (Latin Triticum vulgare), or corn (lat. Zea mays), in

35 g, (2) fertilized fish eggs, selected from carp, (lat.

Cyprinus carpio, wild form), carp roe (Latin Cyprinus carpio, home form), silver carp roe (Latin Hypophthalmichthys molitrix), rudd red caviar (Latin Scardinius erythrophthalmus) and trout roe (Latin Salmo species), in the amount of 18 g , (3) insect larvae in the early stages of development (5–9 days old), selected from larvae of flies (lat. Muscidae), larvae of cocoon moths (Lasiocampidae), larvae of mosquito-jerks (Chironomidae), larvae of tubuloids (Tubificidae), larvae 20 g squeak mosquitoes (Culicidae) and bee larvae (Apidae), and (4) fertilized bird eggs selected from fertilized chicken order eggs (Gall iformes),

fertilized eggs of birds of the order Anatidae or fertilized eggs of birds of the order Anseriformes, were incubated (in vivo or in incubator devices, at a temperature of + 37.3 ° C - + 37.5 ° C, for 5-7 days), in an amount of 25 g, then cooled to a temperature of + 8 ° C and homogenized using an ultrasonic homogenizer or high pressure homogenizer.

 The resulting homogenate was diluted with 0.9% NaCI solution (saline), in the ratio "homogenate: 0.9% NaCI", equal to 1: 3, then placed (for pasteurization) for 2 hours in a water bath at a temperature of + 58 ° FROM; the resulting product was filtered under sterile conditions using cloth filters

needle-punched thermofastened for filtering milk in accordance with TU 17-

14-255, with a filter surface diameter of 30 mm, was added to the filtrate preservative (0.25 ml of 0.05% nipagin), cryoprotectant (5% mannitol), 10 ml were poured into penicillin vials, lyophilized for 60 hours at a temperature of -60 ° C, followed by vacuum dehydration for 20 hours at a temperature shelves -40 ° C, a heating rate of 4 b ° C / hour and a final temperature of the drug + 25 ° C, and then sealed and sterile corked.

 The shelf life of the product obtained in accordance with Example 1 was 6-8 months (at temperatures from + 5 ° C to + 7 ° C).

 Example 2. Biological (growth-promoting, immunostimulating and

increasing the general nonspecific resistance of the organism) the activity of the product in accordance with the invention.

 The biological activity of the product (preparation) in accordance with the claimed

The invention was studied on two types of farm animals - domestic pigs (Sus scrofa domestica) and domestic cows (Bos taurus taurus). The preparation obtained in accordance with example 1 was diluted with distilled water for injection or 0.9% sodium chloride solution and was administered to animals of experimental groups (calves and piglets at the age of 2, 5 and 8 days) subcutaneously or intramuscularly, to the right and left of the spinal column in the dorsal muscle, the right and left neck, thigh, breast muscle under the front limb or other body parts of ^a a portion of the dose rate of 0.05 to 0.1 ml / kg body weight; animals of the control group were injected

corresponding amount of 0.9% sodium chloride solution.

 For 6 months from the start of the experiment, the body weight of animals in the experimental and control groups (20 animals in each group) and its growth, safety (survival) of animals in the experimental and control groups were recorded every month, 1, 2, 4 and 6 months after the start of the experiment.

 For calves of the experimental and control groups (aged 4-6 months), we also examined the parameters of the immune system, including the number (% of the total number of lymphocytes) of B-lymphocytes, T-lymphocytes, as well as the level of circulating immune complexes (CEC), and -globulins, β-globulins and γ-globulins in blood plasma.

The results of the use of the drug in young farm animals are shown in Table 1 and in FIG. 1-5. Table 1. The values of immunity indicators (immunogram) of animals of the experimental and control groups (calves aged 4-6 months).

As a result of the experiment, it was found that by the end of the period

studies (corresponding to the 6-month age of animals taken in the experiment), the difference in live weight between animals of the experimental and control groups was 13.7 kg for piglets and 12.5 kg for calves; the difference in safety (survival) between animals of the experimental and control groups was 6% for piglets and 13% for calves. The level of b-lymphocytes in animals of the experimental group (receiving the product in

in accordance with the invention) was 53.65% higher than in animals of the control group; the level of T-lymphocytes in the experimental group was 54.27% higher than in the control group; the level of CEC (circulating immune complexes) in the experimental group was 51.22% higher than in the control group; the level of alpha globulins in the experimental group was 60.61% higher than in the control group; the level of beta-globulins in the experimental group was 38.64% higher than in the control group; finally, the level of gamma globulins in the experimental group was 87.32% higher than in the control group of animals.

 The presented results of in vivo studies convincingly confirm the presence of immunostimulating, adaptogenic and increasing the general nonspecific resistance of the organism to the activity of the claimed biologically active product.

Claims

Claim: 1. A method of obtaining a biologically active product of natural origin for use in veterinary medicine and animal husbandry, with immunostimulating, immunomodulating, growth-promoting, increasing the general nonspecific resistance of the organism and adaptogenic effect, characterized in that the seeds or seedlings of plants of the cereal family, fertilized fish eggs, insect larvae and fertilized bird eggs are incubated in the early stages of development, followed by cooling, homogenization, homogenate 0.9% sodium chloride solution in a ratio of 1: 2-1: 5, pasteurization, filtration, the addition of a preservative, the addition of cryoprotectant, roses by pouring into bottles, lyophilization and capping. 2. A method of obtaining a biologically active product according to claim 1, characterized in that the seedlings of plants of the cereal family are seedlings at the age of 5-7 days.  3. The method of obtaining the biologically active product according to claim 2, characterized in that the seeds or seedlings of plants of the cereal family are selected from seeds or seedlings of seed rye (Secale cereale), seed oats (Avea sativa), barley ordinary (Hordeum vulgare), ordinary wheat (Triticum vulgare) and corn (Zea mays).  4. The method of obtaining the biologically active product according to claim 1, characterized in that the fish caviar is selected from carp caviar (Cyprinus carpio, wild form), carp caviar (Cyprinus carpio, home form), silver carp caviar (Hypophthalmichthys molitrix), rudd calf ( Scardinius erythrophthalmus) and trout roe (Salmo species).  5. The method of obtaining the biologically active product according to claim 1, characterized in that the insect larvae in the early stages of development are larvae at the age of 5-9 days. 6. The method of obtaining the biologically active product according to claim 5, characterized in that the insect larvae are selected from larvae of flies (Muscidae), larvae of cocoonworms (Lasiocampidae), larvae of mosquito-tussock (Chironomidae), larvae of tubuloids (Tubificidae), larvae of squeak mosquitoes (Culicidae) and bee larvae (Apidae). 7. The method for producing the biologically active product according to claim 5, characterized in that the fertilized bird eggs are selected from the fertilized eggs of the order bird (Galliformes), the fertilized eggs of the bird order (Anatidae) or the fertilized eggs of the order bird (Anseriformes).  8. The method of obtaining a biologically active product according to claim 1, characterized in that the incubation is carried out in vivo or in incubator devices, at a temperature of + 37.3 ° C - + 37.5 ° C, for 5-7 days.  9. The method of obtaining the biologically active product according to claim 1, characterized in that the cooling is carried out at a temperature of + 7 ° C - + 9 ° C, for 4-12 hours.  10. The method of obtaining a biologically active product according to claim 1, characterized in that pasteurization is carried out in a water bath at a temperature of + 56 ° C to + 70 ° C for 1.5-3 hours.  11. The method of producing a biologically active product according to claim 1, characterized in that the filtration is carried out using filters from a needle-punched web of thermally bonded milk for filtering milk in accordance with TU 17-14-255, with a filter surface diameter of at least 27-30 mm.  12. The method of obtaining a biologically active product according to claim 1, characterized in that a 0.01-0.1% nipagin solution is used as a preservative.  13. The method of obtaining the biologically active product according to claim 1, characterized in that 1-5% mannitol, or 1-5% sucrose, or 1-5% glucose, or 1-5% lactose, or 1- is used as a cryoprotectant 5% trehalose.  14. The method of obtaining a biologically active product according to claim 1, characterized in that the lyophilization of the biologically active product is carried out by freezing at a temperature of -60 ° C for 18 hours, followed by vacuum dehydration for 20 hours, at a shelf temperature of -40 ° C, at a heating rate of 4-6 ° C / h and a final temperature of + 25 ° C.  15. Biologically active product of natural origin for use in veterinary medicine and animal husbandry, having immunostimulating, immunomodulatory, growth-promoting, stimulating overall non-specific resistance of the organism to an action, characterized in that it is obtained by the method according to any one of p. 16. The biologically active product according to clause 15, characterized in that it further comprises excipients, excipients, preservatives and other auxiliary components acceptable in veterinary medicine.  17. The biologically active product according to clause 15, characterized in that it is made in the form of a solution for intramuscular injection.  18. The biologically active product according to clause 15, characterized in that it is made in the form of a solution for subcutaneous injection.  19. The biologically active product according to clause 15, characterized in that it is made in the form of a lyophilisate powder for the preparation of a solution for intramuscular or subcutaneous injection.  20. The biologically active product according to any one of p. 15-19, characterized in that it contains:  - seeds or seedlings of plants of the cereal family - 20-35 mass. %;  - fertilized fish eggs - 15-20 mass. %;  - insect larvae - 15-20 mass. %;  - fertilized eggs of birds - 20-25 mass. %;  - a pharmaceutically acceptable carrier - the rest (up to 100%).  21. The biologically active product according to claim 20, characterized in that as a pharmaceutically acceptable carrier contains 0.9% sodium chloride solution. 22. The biologically active product according to claim 20, characterized in that as a pharmaceutically acceptable carrier contains distilled water (sterile pyrogen-free) for injection.  23. The biologically active product according to claim 20, characterized in that it further comprises nipagin as a preservative.  24. The biologically active product according to claim 20, characterized in that it further comprises a cryoprotectant selected from mannitol, or lactose, or sucrose, or trehalose, or glucose.  25. A way to increase survival and growth stimulation in young animals farm animals, including intramuscular or subcutaneous administration to these animals of the biologically active product according to claims 15-24 in a carrier acceptable for veterinary use. 26. The method according A.25, characterized in that the biologically active product is injected subcutaneously or intramuscularly, to the right or left of the vertebral column of the animal in the dorsal muscles, to the right and left of the neck, thigh, into the pectoral muscle under the forelimb, at the Ug dose, at the rate of 0.05-0.1 ml / kg of animal body weight.  27. The method of immunostimulation and increase the overall non-specific body resistance of farm animals, including intramuscular or subcutaneous administration to these animals of the biologically active product according to claims 15-24 in a carrier acceptable for veterinary use.  28. The method according to item 27, wherein the biologically active product is administered subcutaneously or intramuscularly, to the right or left of the vertebral column of the animal in the dorsal muscles, to the right and left of the neck, thigh, into the pectoral muscle under the forelimb, at the dose Ug, at the rate of 0.05-0.1 ml / kg of animal body weight.