RU2580761C1 - Agent for prevention of stress in chickens - Google Patents

Abstract

FIELD: veterinary science.

SUBSTANCE: invention is intended for prevention of stress in chicken. Agent contains components in the following ratio, wt. %: lithium citrate - 8-10; ascorbic acid - 10-15; succinic acid - 10-15; butaphosphane - 30-35; L-carnitine tartrate - 15-20; glucose - the rest.

EFFECT: invention ensures reduction of effective dose of lithium citrate, high availability for organism, higher antistress and antioxidant effects, has stimulating effect on chicken common metabolism and immune system under the influence of factors causing stress development.

1 cl, 4 tbl, 1 ex

Description

The invention relates to veterinary medicine, in particular to stress protectors and antioxidants for chickens, which allow under normal stress conditions to normalize the course of adaptation processes due to specific effects on the central nervous system, general stimulation of metabolism and a pronounced antioxidant effect.

The technical field to which the invention relates.

The invention relates to veterinary medicine, in particular to preparations having a specific anti-stress and pronounced metabolic and antioxidant effect.

Numerous studies have shown that in the process of keeping birds, various stresses play an important role in reducing productivity and cause the development of a number of diseases. In accordance with the established concept, stressors through the nervous and endocrine systems cause morphological and functional changes in organs and tissues, causing an increased need for nutrients and biologically active substances necessary to combat stress, while their intake with food decreases, because In a state, the bird eats poorer food [1]. Stress prevention is based on the use of drugs of different pharmacological groups. Studies conducted in recent years have shown that the most effective approach is the use of pharmacological agents with a specific anti-stress effect in combination with a complex of substances with a common metabolic effect on the body and allowing synergies from their combined use.

The level of technology.

Known drug to improve the health and productivity of farm animals and birds, including under stressful conditions [2]. The drug includes vitamins: A - 0.01-10, D3 - 0.001-0.1, E - 0.1-20, B1 - 0.1-10, B2 - 0.1-20, B6 - 0.1- 20, B9 - 0.02-2, B12 - 0.001-0.1, selenium - 0.01-1, L-lysine - 1-85, DL-methionine - 1-85, ascorbic acid - 1-100, L -carnitine - 0.1-50, betaine - 0.1-50, citric acid - 1-50, formic acid - 1-25, propionic acid - 1-25, vitamin B5 - 0.1-10, potassium sorbate - 0.1-25, monosodium glutamate - 0.1-50, magnesium sulfate - 0.01-1, sodium bicarbonate - 5-75, sodium chloride - 10-120, manganese (as sulfate) - 0.1-10 potassium chloride - 10-100, zinc (in the form of sulfate) - 1-25, vitamin K - 0.1-10 and filler - dextrose monohydrate. The drug is dissolved in water at a dose of 25-100 g per 100 liters of water and evaporated. Oral drinking time varies from 2 to 240 hours depending on conditions. The use of this invention allows to reduce the negative effects of stress, including heat stress and feed contamination by mycotoxicoses, and also improve the health and productivity of farm animals and birds.

The disadvantage of this drug is that it does not include pharmacological substances that have a specific anti-stress effect on the body of birds, but has only a general strengthening effect, including including a non-specific anti-stress effect.

A known substance is lithium glycinate, which, when evaporated with water at a dose of 35-40 mg / kg body weight per head 48 hours before stress, can increase the bird's natural resistance to stress [3].

The disadvantage of this pharmacological agent is that it does not include the use of components with metabolic activity and allowing the use of lithium salt in lower doses. Also, the composition of the pharmacological agent lacks organic acids, which does not allow using it to improve the digestion of birds. The absence of macroergic substances and osmotic pressure regulators in the preparation does not allow its effective use in case of feed and heat stress, in conditions of energy deficiency and osmotic balance disturbance. It also complicates the large-scale use of lithium glycinate, its limited production only in scientific laboratories and the lack of industrial synthesis.

The closest in technical essence and the achieved positive effect and accepted by the authors for the prototype is the use of lithium citrate in poultry at a dose of 25 mg / kg body weight three days before the expected technological stress (debikirovanie, transportation, vaccination) and within 2-3 days after exposure to stress factors [4].

The disadvantages of this pharmacological agent are:

Firstly, lithium citrate is not a true antioxidant. Its specific effect on the central nervous system during the development of a stress reaction has a modeling effect on the antioxidant system of the body and allows its enzymatic link to be activated only during the development of adaptive reactions [5]. Therefore, the prophylactic antioxidant effect of the use of lithium citrate is not expressed, its effect can be detected only with the development of stress in chickens. On the other hand, the adaptive mechanisms of the body, including the activity of the antioxidant system, are limited during the development of a stress reaction and will be limited by the formation of free radicals without entry from the external environment;

secondly, according to classical and modern theories of the development of adaptive reactions, stresses are accompanied by high energy consumption. In birds, the release of catecholamines, glucagon and corticosterone into the blood plays a decisive role in the process of activation of glucogenolysis and glycolysis. The catabolic effect of corticosterone is manifested in the destruction of amino acids to ensure energy expenditure of the body and mobilization of fatty acids [6]. The use of lithium citrate as a stress-protective agent does not provide for increasing the energy potential of the body by stimulating the production of energy by cells, enhancing cellular respiration, as well as by supplying readily available energy sources in the form of macroergic compounds to compensate for the energy costs of the body.

The technical task is to develop a pharmacological composition in the form of a single complex highly soluble in water, including components that are in synergistic relationships, the action of which is aimed at protecting the body of chickens from technological stresses.

The aim of the invention is to increase the anti-stress and antioxidant activity when using water-soluble lithium salts in poultry for the prevention of technological stresses.

The essence of the invention lies in the fact that the developed preparation includes lithium citrate, ascorbic acid, glucose, succinic acid, butafosfan, L-carnitine tartrate in the following proportions, wt. %: lithium citrate - 8-10; ascorbic acid - 10-15; succinic acid - 10-15; butafosfan - 30-35; L-carnitine tartrate - 15-20; glucose - the rest.

Taking into account the components included in the composition of the pharmacological agent, and its mechanism of action, the name most fully revealing the essence of the drug is “Stress-protector antioxidant for chickens” or “SPAO-complex for chickens”.

The invention provides a reduction in the dose and toxicity of lithium citrate, high availability for the body, increased anti-stress and antioxidant effects, has a stimulating effect on the overall metabolism and immune system. To achieve an anti-stress pharmacological effect by the means described in the prototype, 175 mg of lithium citrate per 1 kg of chicken body weight is needed for the entire course of use, which includes 7 doses (3 days before exposure to the stress causing factor, per day and for 3 days after the action stress factor) 25 mg each. The inventive tool allows the use of a smaller amount of lithium citrate due to the potentiation of its action by the constituent components. The application scheme of the SPAO-complex includes 5 applications (2 days before the action of the stress factor, per day and for 2 days after exposure to the stress factor) in a total dose of 74-120 mg per 1 kg of chicken body weight per course.

The pharmacological effect of the drug is due to the fact that the anti-stress effect of lithium citrate is enhanced by the inclusion of additional components with a pronounced antioxidant and anti-stress effect, properties to stimulate all types of metabolism, which are simultaneously macroergic compounds, which leads to a decrease in the applied dose of lithium citrate and allows you to effectively prevent technological stresses in poultry farming.

According to the results of studies available in the literature and based on our own data, lithium citrate has a sedative effect and is able to correct the course of technological stresses in poultry farming [7].

Ascorbic acid plays an important role in the regulation of redox processes. In biological environments, ascorbic acid has an extremely wide spectrum of antioxidant properties: ascorbic acid can restore the α-tocopherol radical, thereby returning the α-tocopherol antioxidant properties. In the presence of Fe3 + or Cu +, ascorbate becomes a powerful prooxidant; it transfers ions to the reduced state and thereby induces the decomposition of organic peroxides. Due to the combination of its properties and due to its high reactivity in an aqueous medium, ascorbic acid is superior to other plasma antioxidants in protecting lipids from peroxidation [8] and as a part of the complex is the main component providing an antioxidant effect.

Succinic acid is a universal intermediate metabolite formed during the interconversion of carbohydrates, proteins and fats and an antioxidant. Helps to strengthen the central link of intracellular energy - increase the oxidation of succinic acid and the activity of succinate dehydrogenase of the respiratory chain of mitochondria; a significant acceleration of the formation of ATP and reducing equivalents, as well as stabilization of the membrane potential of both mitochondral and cell membranes. Succinic acid compounds are adaptogens for hypoxia and intoxication. In poultry, succinic acid is recommended to mitigate the effects of various kinds of stresses on the bird, as a growth and productivity stimulator, as well as an immunoprotector [9].

Butophosphamide (butophane) refers to medications that regulate metabolic processes in the body. It normalizes metabolic and regenerative processes, has a stimulating effect on protein, carbohydrate and fat metabolism, increases the body's resistance to adverse environmental factors. It has an impact on many assimilation processes in the body, stimulates protein synthesis, accelerates the growth and development of birds, significantly improves liver function, increases the nonspecific resistance of the body, and promotes bone formation. In stressful situations, butafosfan normalizes the level of glucocorticoid hormones, thereby improving the utilization of glucose in the blood and activating energy metabolism, stimulates the conversion of ADP to ATP, increases the motor activity of smooth muscles [10].

L-Carnitine is a natural compound that occupies a key place in animal energy metabolism. Lack of this substance leads mainly to a weakening of the conversion of energy and membrane functions. The main role of L-carnitine in energy production is the delivery of fatty acids from the cell cytoplasm to the inner space of mitochondria, in addition to it, it participates in the metabolism of ketones in the body, in the regulation of glycogen synthesis and the formation of ATP, stimulates the oxidation of acetoacetate, and is involved in ketogenesis and thermoregulation in fatty tissues . The use of carnitine in laying hens rations makes it possible to obtain and increases their preservation in the productive period by 2.8%, egg production rate by 2.5% [11]. As part of the drug, it is used as an inducer of energy metabolism and an adaptogen that transports fatty acids into the mitochondrial matrix.

Glucose - in humans and animals, it is the main and most universal source of energy for providing metabolic processes; as part of the complex, it is used as an additional readily available energy source and component that improves the solubility of the drug.

Comparative analysis with the prototype allows us to conclude that the claimed pharmacological agent is characterized in that the components that make up the SPAO complex complement and enhance the effect of each other: the pronounced anti-stress effect of lithium citrate is enhanced by the antioxidant activity of ascorbic and succinic acids; succinic acid, L-carnitine and butophosphamide have a significant effect on metabolism, have adaptogenic properties and, in combination with glucose, allow the formation of a mechanism that helps to compensate for the energy costs of the body, which increase significantly with stress.

An analysis of known pharmacological agents and their combinations allows us to conclude that they lack features similar to the significant distinguishing features in the claimed substance (product).

An example of implementation 1. To assess the stress-protective effect of the SPAO-complex in comparison with the prototype during the development of stress caused by testing for stress sensitivity, we evaluated the stress sensitivity of 1,200 heads of hens at the age of 47 weeks using the method described in the patent of the Russian Federation [12 ]. It is proved that the intradermal administration of turpentine causes the development of a stress response in chickens. The birds were preliminarily divided into 3 equal groups of 400 animals each: the first group received the SPAO complex with water at a dose of 185 mg / kg body weight, according to the scheme 2 days before the turpentine test, on the day of the test, and within 2 days after samples. The second group received a solution of lithium citrate with water at a dose of 25 mg / kg body weight 3 days before the turpentine test, on the day of the test and for 3 days after the test, the hens of the third group served as a control, they did not evaporate the preparations. Bird observation was carried out for 14 days when chickens reached 49 weeks of age.

Indicators reflecting the reproductive qualities of chickens determine the economic efficiency of keeping chickens of the parent herd and to some extent reflect the physiological state. The lowest rates of egg production and reproduction were noted in the control group, in the second group, egg production was higher and averaged 68.6% for the period of the experiment; in the first group, where the SPAO complex was used for stress prevention, the highest production rates were noted. The reproductive qualities of chickens after the action of the stimulus also turned out to be higher in the group where SPAO was used. The data obtained indicate a high stress-protective activity of the claimed invention, exceeding the effectiveness of the prototype.

To evaluate the antioxidant activity (AO) and lipid peroxidation (LP) processes while using anti-stress prophylaxis, lipid peroxidation products were studied, summarized during isolation from the heptane and isopropanol phases [13] and the main enzymes of the antioxidant defense system of chickens [14-16].

To analyze the statistical significance of intergroup differences, one-way analysis of variance was used using the posterior criterion of the least significant difference (Statistica 6.1).

The analysis showed that the use of the SPAO-complex preparation had a pronounced activating effect on the enzymatic link of the antioxidant system, which is confirmed by lower values of lipoperoxidation products in chicken blood plasma (Table 2). The use of lithium citrate (prototype) had a less pronounced effect on lipid peroxidation processes, an activating effect on the antioxidant system was found only on plasma plasma catalase activity. Under the action of the proposed drug in comparison with the prototype, the decrease in lipid peroxidation products in the blood is statistically more pronounced, which is expressed by lower lipid peroxidation index due to activation of the enzymatic link of the AO system.

An example of implementation 2. To assess the stress-protective effect of the SPAO-complex in comparison with the prototype during the development of transport stress, the chickens were divided into 3 groups of 15 animals each: the first group received water with the SPAO-complex in a dose of 240 mg / kg body weight, scheme 2 days before transportation, on the day of transportation and within 2 days after. The second group received a solution of lithium citrate with water at a dose of 25 mg / kg body weight 3 days before the transportation, on the day of transportation and 3 days after, the chickens of the third group served as a control, they did not evaporate the preparations.

Transportation was carried out in the summer, by road along a route of 280 km, the total travel time was about 4 hours. During transportation, the chickens were in 3 cages with an area of 1 m ² each, without lighting and without access to water and feed. To assess the characteristics of the manifestation of adaptive reactions and stress in chickens, leukograms were studied taking into account the percentage of heterophiles to lymphocytes (G / L) in a state of relative rest before transportation, immediately after transportation and two days after transportation. The ratio G / L is a reliable sign that reflects the degree of stress of birds [17]. Blood for the preparation of smears was taken by scallop puncture, smears were stained according to Romanovsky-Giemsa, blood cells were counted using standardized methods, 200 leukocytes were counted in each smear, and smears from 6 chickens were counted in each group.

The level of G / L in the blood of chickens is presented in table 3.

The data presented in table 3 indicate the absence of statistically significant differences in the level of G / L blood of chickens of different groups in a state of relative rest.

Transportation significantly influenced the behavior of the chickens and their appearance. The chickens refused to feed and water, the reaction to stimuli was either absent or insignificant, muscle tremors were observed, and the majority of the subjects showed ruffled feather cover. During transportation, two chickens died in the control group.

In the experimental groups, compared with the control group, a highly reliable statistical difference in the G / L ratio indicator is observed, which indicates a pronounced anti-stress effect of the SPAO complex and the prototype. A direct comparison of the indices of the experimental groups shows a higher value of the G / L ratio in the group of chickens that used lithium citrate, which indicates a more pronounced anti-stress effect of the preparation SPAO-complex.

Two days after transport, a decrease in the G / L ratio was observed in all groups. After applying the SPAO-complex, the values correspond to the indicators before transportation (P = 0.1029), in the group where the prototype was used, the indicators still do not reach the initial data (P = 0.0418). When comparing the prototype and the proposed drug, there is a higher value of the indicator in the group where lithium citrate was used (P = 0.0274), which indicates a higher anti-stress activity of the SPAO complex in the long-term period after stress exposure.

Example 3. To assess the effectiveness of the technical solution and the prototype for vaccination, studies were conducted on hens of the parent herd 29 weeks old vaccinated against infectious bronchitis of hens, Gamboro disease, reovirus infection (tenosynovitis), rhinotracheitis. Vaccination is one of the most common technological stresses in industrial poultry farming and the most unfavorable, since immunosuppression resulting from the activation of stress-implementing mechanisms leads to inhibition of antibody production and a decrease in the activity of specific humoral immunity.

The birds were preliminarily divided into 2 equal groups of 11,000 animals each: the first group received the SPAO-complex with water at a dose of 185 mg / kg body weight, according to the scheme 2 days before vaccination, on the day of vaccination and for 2 days after vaccination. The second group received a solution of lithium citrate with water at a dose of 25 mg / kg body weight 3 days before vaccination, per day and for 3 days after vaccination.

Presented in the table. 4, the data demonstrate in the group where the SPAO complex was used, higher seroconversion rates compared to the group where the prototype was used. The uniformity of the titers and the coefficient of variation, which indicates the uniformity of vaccination, indicates that the development of antibodies occurred as a result of the vaccine, and not as a result of the development of the infectious process.

The coefficient of variation of antibody titers for rhinotracheitis and rheovirus tenosynovitis is in the upper limits of tolerance when using lithium citrate, in contrast to the indicators observed with SPAO, which indicate the development of qualitative specific immunity. The coefficient of variation of antibody titers for infectious bronchitis of chickens and Gamboro disease is lower in the group where the SPAO complex was used, compared with the prototype, which also indicates a better vaccination result and better seroconversion.

Confirmation of these data is the safety level of the parent herd in the productive period from 24 to 54 weeks of life, which in the group where the SPAO complex was used for vaccinations and veterinary treatments is 88.4%, where 83.1% of lithium citrate was used and in the control group where anti-stress prophylaxis was not used 76.7%.

Thus, the invention provides a reduction in the dose and toxicity of lithium citrate, high availability for the body, an increase in antistress and antioxidant effects from the use of lithium citrate, has a stimulating effect on metabolism, which leads to a decrease in losses in industrial poultry farming under the influence of chickens on the body, factors causing stresses.

Literature

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Claims (1)

A remedy for the prevention of stress in chickens containing lithium citrate, characterized in that it further includes ascorbic acid, succinic acid, butafosfan, L-carnitine tartrate and glucose in the following ratio, wt.%:
Lithium citrate 8-10 Vitamin C 10-15 succinic acid 10-15 Butaphosphan 30-35 L-Carnitine Tartrate 15-20 Glucose rest