RU2806816C1 - Method of prevention of respiratory diseases in calves - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: invention relates to veterinary medicine, in particular to a method for preventing respiratory diseases in calves. The method includes the use of hyperimmune serum in combination with an immunomodulatory drug, while a drug containing 60–70% of hyperimmune viral-bacterial polyvalent antidiarrheal serum with an antibody titer of 1:300–1:600 and 30–40% sodium hypochlorite is used as hyperimmune serum at a concentration of 300–350 mg/l, and as an immunomodulatory drug, a biogenic drug made from slaughterhouse waste products is used. Both drugs are administered simultaneously, once, a drug containing hyperimmune serum is administered intramuscularly, and a biogenic drug is administered subcutaneously. For prophylactic purposes, the biogenic drug is injected at a dose of 0.5–0.75 ml per 10 kg of live weight of the calf, and the preparation containing hyperimmune viral-bacterial polyvalent serum is injected at a dose of 3.0 ml per 10 kg of live weight of the animal. Hyperimmune viral-bacterial polyvalent serum is obtained from the blood of donor animals that are unfavorable for viral and respiratory diseases in each particular farm.

EFFECT: expansion of the arsenal of highly effective agents for the prevention of viral respiratory infections in young cattle using cheap raw materials available for livestock farms — slaughterhouse waste.

2 cl, 4 tbl, 1 ex

Description

The invention relates to veterinary medicine, in particular to methods for the prevention of respiratory diseases in calves by increasing immunobiological reactivity for the specific prevention of respiratory viral infections in young cattle.

There is a known method of increasing the immunobiological reactivity of calves for the specific prevention of viral respiratory diseases; for this, an immunostimulating drug and an aqueous solution of silver containing no more than 0.8 mg of silver ions per 100-120 ml of boiled water per 30-40 kg of animal weight are used, which within For 10 days, the animal is fed in an amount of 19-20 ml, then the immunostimulating drug “Immunofan” is administered intramuscularly three times with an interval of 24 hours at a dose of 0.9-1.0 ml per animal, then the nine-valent serum against infectious rhinotracheitis is administered intramuscularly and parainfluenza-3, salmonellosis, pasteurellosis and E. coli in cattle: on the first day in a dose of 49-50 ml per animal, again in the same dose after 10 days and the vitamin-amino acid complex “Bitam” is administered intramuscularly in a dose of 2, 9-3 ml per 10 kg of animal weight twice a day for five days, then 14 days later, after repeated administration of the nine-valent serum and the vitamin-amino acid complex “Bitam”, the Cattlemaster Gold vaccine is administered subcutaneously to the calves twice with an interval of 21 days FP5 L5" at a dose of 4.9-5 ml per animal. (Patent No. 2712237. IPC A61K 33/38, A61K 39/12, A61K 31/00. Published 01/27/2020, Bulletin No. 3).

The disadvantage of this method is the narrow spectrum of action of serum antibodies against viral infections (2 nosologies), the very long process of drinking silver solution (10 days), immunostimulation (3 days), in such a long process of preparing animals for the introduction of nine-valent serum in an unfavorable epizootic situation on the farm an outbreak of acute bovine respiratory viral infections (CARI) may occur.

A medicine is known for the prevention and treatment of diseases of viral etiology in cattle and a method for the prevention and treatment of these diseases, which includes a polyvalent serum against infectious rhinotracheitis, parainfluenza-3, viral diarrhea and adenoinfections of cattle and the immunostimulant Vivaton in the following ratio of components , wt.%, polyvalent serum against infectious rhinotracheitis, parainfluenza-3, viral diarrhea and adenoinfections of cattle - 80-85, Vivaton - the rest. The drug is administered to calves subcutaneously: for prophylactic purposes - twice with an interval of 10-14 days at a dose of 0.5 ml/kg of live weight, while the first administration of the drug to calves is carried out within 24 hours after birth or admission to the farm, and with therapeutic the purpose of the drug is administered at a dose of 1 ml/kg of live weight twice with an interval of 48 hours, and in adult animals the drug is administered subcutaneously at a dose of 20.0 ml twice with an interval of 7-14 days. The product and method form strong immunity against diseases of viral etiology and do not cause allergic reactions or side effects. Vivaton activates a number of indicators that characterize the natural nonspecific resistance of the animal body. (Patent No. 2404807. IPC A61K 39/395, A61K 31/12, A61K 36/00. Published November 27, 2010. Bulletin No. 33).

With positive results from the use of polyvalent serum in combination with Vivaton-S, the disadvantages of this method include a fairly high dose of administration per 1 kg of live weight, while the full potential of the serum is not used, since the titer of virus-neutralizing antibodies decreases by 20.0% per due to dilution with an immunomodulator. The presence of cytokine proteins in Vivaton-S, which attract monocytes, macrophages and T-cells to the site of infection, contribute to the further development of inflammation, and this, as is known, can lead to the so-called cytokine storm, when the level of cytokines in the blood increases sharply, which leads to an attack of the immune system on the cells and tissues of one’s own body. The consequence of this can be the destruction of tissues and organs, and lead to the death of the body.

There is a known method for the prevention of respiratory diseases in calves, including the use of xymedone hydrochloride in clinically healthy calves 20-30 days of age, used in a mixture with 3.5% alcohol tincture of Scots pine buds (Gemmue Pini), herbs and inflorescences of Echinacea purpurea L. , rhizomes and roots of elecampane (Inula Neleium L.), taken in a ratio of 2:1:1, at the rate of 2.0 g of xymedon hydrochloride per 100.0 ml of 3.5% alcohol tincture at a dose of 1.5-2.0 ml/kg of live weight for the first time 18-24 hours before and twice after immunization, which is carried out three times by subcutaneous injection of hyperimmune serum, at a dose of 1.0 ml/kg of live weight with an interval of 10-12 days. (RU Patent No. 2620548. IPC A61K 36/15, A61K 36/185, A61K 39/42, A61K 31/12. Published 05/26/2017, Bulletin No. 15).

The disadvantage of this known method is that it is multi-stage and labor-intensive in its technical execution. Preventive administration of serum to calves begins quite late (20-30 days of age), when animals can already become infected or even get sick, since some viruses of respiratory infections overcome the placental barrier and calves become infected in utero, preventive treatment in this situation will be ineffective and impractical .

In addition, the use of immunomodulators based on plant materials containing hundreds of biological ingredients, the effect of which on the body, both individually and in combinations, is often unknown; the complex mechanism of action of herbal medicines is difficult to study in detail. In addition, the composition of plants is not stable; it can be greatly influenced by changing soil composition, external sources, weather, pollution, etc. Pharmacologists note that the interaction of herbal medicines with drugs can lead to clinically significant changes in the pharmacological response - a decrease in the effectiveness and safety of pharmacotherapy, as well as the development of adverse reactions [1].

A known drug and method for preventing diarrhea in calves. The drug includes a sodium hypochlorite solution at a concentration of 300-350 mg/l and hyperimmune polyvalent blood serum with a titer of deterministic antibodies of 1:300-1:1200, with the following ratio of components, wt.%: sodium hypochlorite solution 30-40, hyperimmune polyvalent serum - the rest, then hyperimmune polyvalent serum based on hypochlorite. For prophylactic purposes, on the first day of life, newborn calves are administered once, subcutaneously or intramuscularly at the rate of 3 ml per 10 kg of live weight or orally 20-30 minutes before the first drinking of colostrum in a dose of at least 50 ml per head.

The sodium hypochlorite solution used in the above source of information has an alkaline reaction, bactericidal, antiviral, antifungal, deodorizing, detoxifying effect, helps neutralize toxic substances by indirect oxidation of toxins in tissues (see Instructions for the use of active sodium hypochlorite solution, protocol No. 2 from April 23, 1999, approved by the Veterinary Farm Council of the Veterinary Department of the Ministry of Agriculture and Food of the Russian Federation). (RF Patent No. 2196591, IPC A61K 33/14, A61K 36/16, publ. 2003.06.25).

With all the positive aspects after using a polyvalent serum with full coverage of the spectrum of microflora circulating on the territory of the farm, the disadvantages include weak immunomodulatory activity on immunocompetent cells and systems, as well as the fact that it does not have a stimulating effect on the metabolism in the body of animals .

A known method for the production of biogenic medicinal products includes the use of raw materials from slaughterhouse waste, keeping the raw materials in the refrigerator for 5-7 days at a temperature of +2, +4°C, grinding the raw materials and then mixing them with an extractant, filtration, packaging and sterilization in an autoclave for an hour at a temperature of 120°C, while an active solution of sodium hypochlorite is used as an extractant at a concentration of 300-600 mg/l in a raw material: hypochlorite ratio of 1:2-1:3, and extraction is carried out at a temperature of +2, +4 °C for 18-24 hours. The biogenic drug was tested in the treatment regimen for calves with diarrheal syndrome from the first day of therapy, subcutaneously in the middle third of the neck in a dose of 2-4 ml for calves aged 2 to 45 days. (Patent No. 2682641, IPC A61K 35/12. Application 2018122212 dated 06/15/2018. Published 03/20/2019, Bulletin No. 8).

The biogenic preparation obtained by this method, like other biogenic preparations, cannot be used as a primary means due to its low effectiveness in the specific prevention of viral respiratory infections, but only as an immunomodulatory agent, since biogenic (tissue) preparations do not have a direct effect against pathogens, but only normalize immunobiological processes in the animal body.

When preventing respiratory viral diseases of calves, they use both specific therapy (vaccines, hyperimmune serums, immunoglobulins) and drugs that increase nonspecific (natural) resistance (vitamins, immunomodulators, dietary supplements), which contributes to faster formation and better manifestation its defense mechanisms.

Immunomodulators are widely used in veterinary medicine to improve digestion, normalize metabolism, and increase the resistance of animals to adverse environmental factors [2]. Therefore, it is relevant for the prevention of calves with diseases caused by the association of various microorganisms, is the development and use of environmentally friendly immunostimulating agents. In this regard, of great scientific and practical interest is a cheap, previously patented biogenic preparation made from slaughterhouse waste of farm animals: containing natural physiologically active compounds, organic acids, a complex of carboxylic acids that carry out oxidation, compounds such as albumin and peptones, hormone-like substances, polypeptides, amino acids, etc. The combined use of a biogenic drug with hyperimmune serum allows you to quickly stop the infectious process, as well as increase the nonspecific resistance of cellular and humoral factors of the animal’s body’s immune defense.

The task to which the claimed invention is aimed is to expand the arsenal of means (methods) with high efficiency in the prevention of viral respiratory infections of young cattle using cheap raw materials (slaughterhouse waste) available to livestock farms.

The problem is solved by the fact that a method for the prevention of respiratory diseases in cattle calves includes the use of hyperimmune serum in combination with an immunomodulatory drug, while a drug containing 60-70% of hyperimmune viral-bacterial polyvalent serum against diarrhea with an antibody titer of 1 is used as a hyperimmune serum : 300-1:600 and 30-40% sodium hypochlorite at a concentration of 300-350 mg/l, and a biogenic drug made from slaughterhouse waste is used as an immunomodulatory drug, while both drugs are administered simultaneously, a single drug containing hyperimmune serum intramuscularly, and a biogenic drug subcutaneously, and for prophylactic purposes, a biogenic drug is injected at a dose of 0.5-0.75 ml per 10 kg of live weight of the calf, and a drug containing hyperimmune viral-bacterial polyvalent serum at a dose of 3.0 ml per 10 .0 kg of live weight of the animal. Hyperimmune viral-bacterial polyvalent serum is obtained from the blood of donor animals, in those unaffected by viral respiratory diseases, in each specific farm.

A biogenic medicinal product from slaughterhouse waste is prepared by keeping the raw materials in the refrigerator for 5-7 days, grinding the raw materials and then mixing them with an active solution of sodium hypochlorite in the ratio raw materials: sodium hypochlorite 1: 2-1: 3 and extraction at a temperature of +2, +4°C for 18-24 hours, packaging, sterilization in an autoclave for 1 hour at a temperature of 120°C.

In production experiments, we used for comparison polyvalent factory serum (Pokrovsky Biological Preparations Plant) and hyperimmune viral-bacterial polyvalent serum obtained from donor animals of the farm in which calves were prevented and the identification of their (serums) more effective compatibility with a biogenic preparation was carried out.

Scientific and production experiments to study the preventive effectiveness of using the claimed method are presented in Table 1.

Blood sampling for research in newborn calves was carried out twice before the administration of drugs and on the 14th day after injection of drugs (Tables 2, 3). Clinical observations of the experimental animals were carried out for a month.

The data obtained indicate that in 10.0% of newborn calves a decrease in the total number of leukocytes was recorded by 2.2% below the physiological norm, respectively, hemoglobin in 40.0% by 2.0-7.0%, and the total amount of protein in 40 .0% by 2.0-10.2%.

After injections of serum drugs alone and in combination with a biogenic drug, a significant increase in the total number of leukocytes was noted by 12.9% in O-2, O-3, O-4 (P≤0.01). Physiological leukocytosis within the reference values indicates an increase in immune system cells responsible for protecting the body, capable of forming a so-called “line of defense” against viruses, bacteria, toxins, foreign bodies, and waste waste. The total amount of hemoglobin in the 0-2 group compared to the initial and O-1 group indicators increased by 4.4-6.1%, which indicates an improvement in erythropoiesis. In addition to such important functions as transporting oxygen and iron throughout the body, hemoglobin maintains acid-base balance and removes carbon dioxide from tissues and organs. Blood proteins perform many functions: they maintain a constant osmotic pressure, blood pH, the level of cations in it, play an important role in the formation of immunity, are structural components of cell membranes, etc. [3]. An increase in the total amount of protein was recorded in the O-1 group of calves by 7.6%, O-2 by 14.2%, O-3 by 9.0% (P≤0.01), O-4 by 12.0% (P≤0.05). A decrease in the albumin fraction of protein was noted in the O-1 group of calves by 5.6% (P≤0.05), O-2 by 1.2% (P≤0.01), O-4 by 2.2% (P ≤0.05). Serum albumins are the main blood proteins whose function is to maintain blood oncotic pressure, transport various chemicals and participate in metabolic processes. A significant decrease in albumin, within the physiological norm to the initial values, indicates the intensity of protein metabolism, growth and development of young cattle.

The gamma globulin fraction consists of immunoglobulins, which are functionally antibodies that provide the body's humoral immune defense against infections and foreign substances; a significant increase in this fraction was noted in the O-2 group by 10.0% and O-4 by 8.5% (P ≤0.01).

Determination of bactericidal activity of blood serum (BAS) is an indicator of the activity of phagocytosis, namely neutrophils and monocytes, and indicates the antimicrobial properties of blood and the general state of the immune system. BASK significantly increased in calves in O-1 by 4.3% (P≤0.01), respectively in O-2 by 6.6% (P≤0.05), in O-3 by 3.8%, O-4 by 5.0% (P≤0.01) relative to the initial values. Serum lysozyme activity (LAS) was also significantly higher in all experimental groups 14 days after administration of the drugs in the O-1 group of calves by 6.7%, in the O-2 by 12.6%, in the O-3 by 6, 2%, O-4 by 11.0% (P≤0.05), also a significant difference was noted between O-1 and O-2, O-3 and O-4 groups (P≤0.05) and O- 2 and O-4 (P≤0.01). Thus, the use of polyvalent serums and a biogenic preparation for the purpose of preventing ARVI in cattle helps to strengthen the level of natural resistance during the period of adaptation of the body of newborn calves to new conditions and the formation of immune defense. In animals that received a biogenic drug in addition to polyvalent serum, nonspecific protection rates were higher than in calves without the use of an immunomodulator (BASK by 1.2-2.3%, LASK by 4.8-5.9%).

The percentage of different types of leukocytes presented in Table 3, no significant differences were recorded, both with the initial indicators and between the experimental groups, after using the serum separately and in combination with a biogenic drug, which indicates the safety and physiological nature of the combined use of a biogenic drug, which is a natural component of the animal's body.

The average daily weight gain of calves in the first month of rearing significantly increased (P≤0.01) in the O-2 and O-4 experimental groups, where an additional biogenic drug was administered simultaneously with the polyvalent anti-ARVI serum, in relation to the O-1 group of animals. The maximum absolute increase in live weight of calves was obtained in the O-2 experimental group, which is 6.0% higher than in O-1, respectively 8.2% than O-3 and 5.0% higher than in O- 4. The relative growth rate, which allows us to estimate the intensity and energy of growth of growing young cattle, in the O-2 group was higher by 2.3% compared to O-1, respectively by 4.1 to O-3 and 3.3% to O-4. It is necessary to note the positive effect of the biogenic drug in combination with polyvalent serum on the dynamics of the average daily and relative growth of animals, respectively, by 3.3% and 0.8% in the O-4 group compared to O-3.

The minimum incidence of ARVI in calves was noted in the O-2 group (5.0%), where a biogenic preparation with hyperimmune serum obtained from the blood of donors of the given farm, containing the entire spectrum of antibodies corresponding to the viral-bacterial background of the farm, was used as a prophylactic agent, 10 each. 0% of animals got sick in O-1, O-4, the maximum number of 40.0% of sick people was noted in O-3 group, where polyvalent factory serum with a limited set of antibodies against viral infections of cattle was used as a prophylactic agent.

The data obtained indicate that in experimental calves, with specific prevention of ARVI using polyvalent sera in combination with a biogenic preparation, effective (stable) immunity is formed, and in calves, where only polyvalent specific sera were used, a breakthrough of immunity was recorded, apparently associated with immunosuppressive state of calves in the early postnatal period.

Example 1. In a hospital station unfavorable for ARVI in cattle, newborn calves with a live weight of 37-40 kg on the first day of life were administered intramuscularly at a dose of 3.0 ml per 10 kg of body weight (11.1-12.0 ml) for prophylactic purposes. hyperimmune serum obtained in a dysfunctional farm for viral respiratory diseases of cattle in combination with a biogenic drug at a dose of 0.5 ml per 10 kg of live weight (1.9-2.0 ml) subcutaneously, once.

Thus, the studies conducted indicate the high effectiveness of the proposed method for the prevention of respiratory viral infections in calves when using a biogenic drug in combination with hyperimmune serum containing antibodies to vaccine strains, as well as pathogenic and conditionally pathogenic microflora circulating in the population of the environmental biotope, isolated (limited) territory of the farm, and can be successfully used for the preventive purpose of respiratory viral infections in newborn calves, to create passive antimicrobial immunity, and the introduction of a biogenic drug with immunomodulatory activity, capable of affecting the metabolism of cells and tissues of the body, for example, stimulating the synthesis of immunoglobulins , blood serum lysozyme, which has antimicrobial activity, has immunomodulatory, anti-inflammatory, antitoxic effects, stimulates regeneration processes, hematopoiesis, etc.

The use of the claimed method will make it possible to expand the arsenal of means (methods) aimed at reducing morbidity with high efficiency in preventing viral respiratory infections of young cattle using cheap raw materials (slaughterhouse waste) available to livestock farms.

Information sources

1. Morozov S.V., Tkacheva N.I., Tkachev A.V. Problems of complex chemical profiling of medicinal plants // Chemistry of plant raw materials. 2018. No. 4. pp. 5-28. DOI: 10.1425 8/j cprm.2018044003

2. Daricheva N.N., Ermolaev V.A. Tissue therapy in veterinary medicine. Monograph. - Ulyanovsk, UGSHA. 2011. - 168 p.

3. Nozdrachev A.D., Bazhenov Yu.I., Barannikova I.A. and others. General course of human and animal physiology. Book 2. Physiology of visceral systems. - M.: Higher school, 1991. - P.136-146.

Claims (2)

1. A method for the prevention of respiratory diseases in calves, including the use of hyperimmune serum in combination with an immunomodulatory drug, wherein a drug containing 60-70% hyperimmune viral-bacterial polyvalent serum against diarrhea with an antibody titer of 1:300-1:600 is used as a hyperimmune serum and 30-40% sodium hypochlorite at a concentration of 300-350 mg/l, and a biogenic drug made from slaughterhouse waste is used as an immunomodulatory drug, while both drugs are administered simultaneously, once, a drug containing hyperimmune serum intramuscularly, and a biogenic the drug is administered subcutaneously, and for prophylactic purposes, the biogenic drug is injected at a dose of 0.5-0.75 ml per 10 kg of live weight of the calf, and the drug containing hyperimmune viral-bacterial polyvalent serum is injected at a dose of 3.0 ml per 10 kg of live weight of the animal , and hyperimmune viral-bacterial polyvalent serum is obtained from the blood of donor animals, unfavorable for viral respiratory diseases, in each specific farm. 2. The method according to claim 1, characterized in that the biogenic medicinal product from slaughterhouse waste is prepared by keeping the raw material in the refrigerator for 5-7 days, grinding the raw material and then mixing it with an active solution of sodium hypochlorite in the ratio raw material: sodium hypochlorite 1: 2-1:3 and extraction at a temperature of +2, +4°C for 18-24 hours, packaging, sterilization in an autoclave for 1 hour at a temperature of 120°C.