RU2506084C1 - Drug preparation for prevention and treatment of hypovitaminosis and normalisation of metabolism in poultry - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics, and aims at the prevention and treatment of hypovitaminosis and the normalisation of metabolism. The drug preparation contains vitamin A, vitamin D₃, vitamin E, vitamin C; a selenium compound is presented by DAFS-25 in the following ratio of the ingredients in 1 l of the solution: vitamin A - 25.0-35.0 ml, vitamin D₃ - 0.03-0.05 ml, vitamin E - 55.0-65.0 g, vitamin C - 90.0-110.0 g, DAFS-25 - 0.2-0.4 g, polysorbate-80 - 190.0-210.0 ml, 2-pyrrolidone 39.0-41.0 ml, distilled water - up to one litre.

EFFECT: using the declared invention enables increasing the immune status in poultry, normalising the antioxidant and detoxifying systems, improving the livability, egg production and meat production along with reducing the feed consumption per a unit of product.

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Description

The invention relates to the field of pharmaceuticals and can be used in poultry farming to compensate for the deficiency of vitamins and selenium in animals.

The Ministry of Agriculture of the Russian Federation for the period until 2020 developed a concept for the development of poultry farming, which provides for an increase in the production of poultry meat and eggs. This concept requires the introduction of innovative poultry feeding technologies. Meanwhile, the realization of the productivity potential of broilers, laying hens and improving the composition of meat, as well as the food and incubation qualities of eggs is constrained by the use of compound feeds in the diets, the recipe of which is based on local grain feeds, which have a high content of heavy metals, an insufficient amount of antioxidant substances, and a large microbial Mycotoxin contamination and infection. Eating such feeds reduces the secretion of digestive enzymes by 15-50%, causes dystrophic changes in the liver and kidneys, has an immunosuppressive effect, leads to a decrease or destruction of the antioxidant defense of the body, an increase in its predisposition to various diseases, a decrease in both productivity and ecological purity of the resulting products. In addition, a deficiency in the diets of laying hens of vitamins A, D ₃ , E, C and selenium (due to their instability), which are the most important corrective links in optimizing the antioxidant status of an organism and its resistance to diseases, is accompanied by a deterioration in the incubation quality of eggs and the appearance of physiologically immature repair young animals. This problem is becoming especially acute because Russia, having joined the WTO, should, like the EU countries, exclude the use of antibiotics in animal diets.

Thus, the question of finding the possibility of improving the incubation quality and hatchability of chicken eggs - laying hens of the parent herd, as the most important factor in the reproduction and growth of the industrial population, is relevant.

Among the many drugs that are diverse in their origin, physicochemical, physiological properties and the effect on the bird’s body, in particular on the state of metabolism in the body, on the immune system and non-specific resistance factors, preparations of synthetic amino acids (lysine, methionine, tryptophan ), fat-soluble vitamins (carotene. A, D, E, K), water-soluble vitamins (groups B ₁ ... B ₁₂ , C, H, F, U), salts of deficient trace elements Fe, Cu, Co, Zn, Mn, Se, Mo (see. Theory and practice of using biologically active substances in animal husbandry, Kirov, October 6-7, 1998: Abstracts of the scientific conference of Kirov, 1998. - 98 p.).

However, most of these drugs selectively affect certain indicators of immunity.

Known vitamin-mineral complexes for birds of foreign production, such as:

- nutril selen (Slovenia) - is a combination of 12 vitamins, 3 essential amino acids and selenium - Internet address: http://zoovet.uaprom.net, April 21. 2012;

- rex vital electrolytes (Spain) - a complex preparation containing the most important vitamins, trace elements and amino acids - see, REX VITAL ELECTROLYTES, Handbook of the AIC, National, Internet address: http://sprav.agronationale.ru/drugs/21309. html, 2008.

- movisel (Croatia) - a complex preparation containing the most important vitamins and minerals - Internet address: http: // www.hellotrade.com;

- ganasupervit (Spain) - a complex of 19 vitamins and minerals, Internet address: http: // www.veterinar.ru, 2002.

The above vitamin-mineral complexes are highly effective, but have a complex composition and high cost.

A new generation antioxidant drug is known, namely, the Carcesel preparation containing beta-carotene, vitamins C, E and DAFS-25 dissolved in vegetable oil (see RU 2342119 C2, 12/27/2008).

Kartsesel positively affects the regulation of the productivity of laying hens, the safety of young animals, the daily increase in the mass of chickens, and the commercial and nutritional quality of eggs.

However, the composition contains no vitamins A and D ₃ . In addition, carcasesel mixes poorly with compound feed, and in case of uneven mixing, there is a threat of selenium poisoning.

Known drug Turboshock Se (France). Turboshok Se is a liquid vitamin supplement with selenium for oral use. It mixes well with water. All components of the drug are in the form of a water-dispersion system. The Turbocharger Se contains fat-soluble vitamins A, D ₃ , E, sodium selenite and propylene glycol, which are necessary to meet the needs of farm animals and birds in critical periods of productivity. The content of selenium Turboshok Se is the most concentrated product on the Russian market.

Internet address - http://www.vitalagro.ru/product/page7/page98/, 2011

This drug is the closest analogue of the proposed drug.

However, vitamin C is absent in the composition of the well-known preparation Turboshock Se, and its sodium selenite is highly toxic.

The objective of the invention is the development of a medicinal product that ensures the normal course of metabolic processes in a living cell, participates in a complex complex of enzymatic systems, improves the overall health of the bird and increases its productivity.

The problem is solved in that the drug for the prevention and treatment of hypoavitaminosis and the normalization of metabolism in birds, containing vitamin A, vitamin D ₃ , vitamin E, selenium compound and target additives, according to the invention, additionally contains vitamin C, and as a selenium compound contains DAFS-25 in the following ratio of ingredients in 1 liter of solution:

Vitamin A 25.0-35.0 ml Vitamin D ₃ 0.03-0.05 ml Vitamin E 55.0-65.0 g Vitamin C 90.0-110.0 g DAFS-25 0.2-0.4 g Polysorbate-80 190.0-210.0 ml 2-pyrrolidone 39.0-41.0 ml Distilled water to liter

Vitamin A is involved in redox reactions; inhibiting the activity of insulin, affects carbohydrate and fat metabolism; activates the metabolism of calcium and magnesium, is part of the lipid layer of cell membranes and thereby regulates the structure, function and regeneration of epithelial tissues and increases resistance against infection. Increased doses prevent weight loss and increase metabolism.

Vitamin D ₃ regulates the exchange of calcium and phosphorus, starting from the moment of absorption from the intestine and ending with the removal of animals from the body, affecting the formation and development of the skeleton.

Vitamin E regulates redox processes and affects carbohydrate-fat metabolism, enhances the effect of vitamins A and D ₃ . Vitamin E performs the function of an antioxidant, provides resistance and activity of the epithelium of the mucous membranes of the reproductive system, gastrointestinal tract and conjunctiva. Together, vitamins A, D ₃ and E increase the body's resistance to infectious diseases, improve the general condition of animals, and have an auxiliary effect in rickets and osteomalacia.

Vitamin C is a powerful antioxidant. It plays a role in the regulation of redox processes, participates in the synthesis of collagen and procollagen, the exchange of folic acid and iron, as well as in the synthesis of steroid hormones and catecholamines. Vitamin C also regulates blood coagulability, normalizes capillary permeability, is necessary for hematopoiesis, has anti-inflammatory and anti-allergic effects. Thus, vitamin C is an important factor in the normal growth and increase the protective functions of the body.

Selenium is involved in the metabolism of proteins and nucleic acids, is part of enzymes and hormones, and is involved in immunity and regeneration reactions. With a lack of selenium in the bird of the parent herd, the fertility of eggs decreases sharply and the death of embryos at the last stage of development increases. Selenium-containing proteins form bone and cartilage, support the work of skeletal and smooth muscles, and control hormonal balance. In DAFS-25, selenium is in organic, i.e. more bioavailable form. In addition, DAFS-25 compares favorably with sodium selenite and sodium selenate with significantly lower toxicity and indifference to the components of feed mixtures.

The technical result of the claimed invention is to expand the arsenal of tools for the prevention and treatment of hypoavitaminosis and the normalization of metabolism in birds, i.e. obtaining a domestic harmless non-toxic vitamin-mineral complex, which makes it possible to compensate for the deficiency of vitamins and selenium in the body of birds, and thereby increase its protective functions and prevent the development of diseases developing against their background.

The claimed invention is characterized by the following examples, which, however, do not limit the scope of the claims of the applicant.

Example 1

Prepare the drug by constant stirring on a magnetic stirrer the estimated number of components at a temperature of 50 ° C. First, 200 ml of polysorbate-80 are mixed with 0.04 ml of vitamin D (5 mln / ml), 30 ml of vitamin A (1.7 mln / ml) and 60 g of vitamin E (98%). Then, pre-mixed 0.3 g of DAFS-25 and 40 ml of 2-pyrrolidone are added to the resulting solution. After that, an aqueous solution of 100 g of vitamin C is added to the resulting solution, distilled water up to 1 L is added, and mixed.

The resulting drug is a balanced combination of essential vitamins and nutrient selenium. Contains active ingredients: vitamins A, D ₃ , E, C, DAFS-25 and auxiliary components: polysorbate-80 (Tween-80), 2-pyrrolidone and distilled water.

The drug is a clear, opalescent liquid from light yellow to yellow, mixes well with water.

The resulting drug is used to prevent and treat hypoavitaminosis, normalize metabolism in birds under stress, reduce productivity: with growth retardation and insufficient weight gain; with infectious and invasive diseases; with veterinary measures: preventive vaccinations and deworming; with low egg production and insufficient strength of the egg shell.

For prophylactic purposes, in chickens and young chickens, the drug is administered orally in a mixture with water for drinking once a month. When breeding laying hens for prophylactic purposes, the drug is given twice with an interval of 2 weeks. For therapeutic purposes (for all age groups), the frequency of use is increased to 2-3 times a month.

Dilution of the drug in water is carried out fractionally: first, the drug is diluted in a small amount of water (1: 100), and then the amount of water necessary for watering the bird is added to the resulting solution.

Recommended doses of the drug, taking into account age and method of administration (ml / 100 heads): chickens - 10 ml, young laying hens - 15 ml, laying hens - 20 ml, turkeys - 30 ml.

Side effects and complications when using the drug in accordance with the above doses were not detected.

Example 2

A study of the chronic toxicity of an oral vitamin supplement with selenium in laboratory animals.

In the study of the chronic toxicity of vitamin complex A, D ₃ , E, C with selenium, an experiment was performed on 24 white mongrel male mice with an initial weight of 20-25 g.

All animals were divided into 4 groups, 6 animals each. Since during the study of the acute toxicity of the drug, no animal deaths were observed (even at the maximum possible doses), we selected doses based on the daily requirement of animals for vitamins. Previously, the drug was diluted in physiological saline 1: 100 to increase the volume of input substance.

The animals of the 1st experimental group were intragastrically administered through the probe daily for 1 month a vitamin complex in a 5-fold dose of the daily requirement for vitamins.

The animals of the 2nd group were intragastrically administered a vitamin complex in a 10-fold dose of the daily requirement for vitamins

For animals of the 3rd experimental group, the drug was intragastrically administered at a dose 15 times the daily requirement for vitamins.

Animals of the 4th group - control - under the same conditions of keeping and feeding were injected with an equal volume of saline.

Throughout the experiment, we monitored the condition and behavior of animals, the dynamics of growth in body weight, regularly conducted studies to evaluate the functional state of the liver (hexin sample), kidneys (clinical evaluation), and studied the effect of the drug on hematological parameters. Statistical processing of the data was carried out according to Student-Fisher.

The results of the studies showed that during the experiment no external signs of intoxication were observed in animals. All animals of both the experimental and control groups were active, the hairline was brilliant, smoothed. Reaction to external stimuli saved.

No signs of toxicosis and death of animals were observed, which suggests that the drug has no toxic effect of cumulation in the indicated doses.

The drug had a positive effect on the increase in live weight, as evidenced by the positive dynamics of the results of weighing animals (table 1).

Table 1 The effect of the vitamin complex on the weight gain of mice by oral administration for a month (n = 6). Weighing time The body weight of mice, g 1 group 2 group 3 group the control 0 24.1 ± 1.04 24.6 ± 0.98 23.9 ± 1.1 25.1 ± 1.09 1 Week 24.95 ± 0.64 25.3 ± 1.1 24.31 ± 1.7 25 ± 1.12 2 weeks 26.98 ± 1.01 27.6 ± 0.61 27.85 ± 1.44 25.01 ± 1.64 3 weeks 31.1 ± 1.34 31.24 ± 1.24 30.96 ± 2.24 25.18 ± 1.68 4 weeks 31.82 ± 2.94 31.28 ± 2.62 31.13 ± 2.25 25.01 ± 2.38 Note: P> 0.05.

At the end of the experiment, animals were slaughtered, in which blood was taken for biochemical and hematological studies, as well as organs were taken for morphological examination.

In order to assess the functional state of the liver, the concentration of total protein and its fractions, glucose and cholesterol in the blood serum of mice was determined, the enzyme spectrum included determination of the activity of indicator enzymes ACT (aspartate aminotransferase) and ALT (alanine aminotransferase).

The state of the functional activity of the kidneys was judged by the concentration of creatinine and urea in the blood serum of animals. Biochemical studies were performed using Hospitex diagnostics reagent kits on a Myndrey biochemistry analyzer. The analysis of biochemical blood parameters of animals of different groups with prolonged administration of the vitamin complex did not reveal statistically significant differences from those parameters in animals of the control group (table 2). These data indirectly indicate the absence of disturbances in the functional state of the kidneys and liver.

table 2 Indicators of the functional state of the kidneys and liver of mice with the introduction of a complex of vitamins (n = 6, P> 0.05) No. p / p Indicators Units rev. 1 group 2 group 3 group 4 group one Glucose mmol / l 4.56 ± 1.99 4.98 ± 1.08 5.32 ± 1.53 5.02 ± 0.53 2 Cholesterol mmol / l 2.00 ± 0.82 2.0 ± 0.40 2.0 ± 0.41 2.03 ± 0.41 3 Urea mmol / l 7.15 ± 1.03 8.67 ± 1.98 6.77 ± 1.01 7.74 ± 1.03 four Creatinine μmol / l 101.25 ± 9.71 98.34 ± 3.89 97.00 ± 4.03 78.00 ± 6.12 5 Common protein g / l 73.05 ± 7.07 78.98 ± 5.56 79.03 ± 4.61 78.03 ± 8.61 6 Albumen g / l 36.83 ± 5.64 34.86 ± 4.61 31.77 ± 9.80 36.77 ± 9.80 7 Globulin g / l 36.22 ± 4.27 44.12 ± 4.18 47.26 ± 2.34 41.2b ± 4.12 8 ALT E / L 112.75 ± 6.43 126.16 ± 8.84 123.8 ± 9.12 118.8 ± 9.41 9 ACT E / L 236.00 ± 8.40 243.54 ± 8.98 231.83 ± 7.29 228.63 ± 9.19

The effect of the vitamin complex on peripheral blood was assessed by the morphological composition of the cells and the level of hemoglobin on the Naet Screen apparatus. As the results of the study showed, chronic administration of the drug did not cause significant differences in hematological parameters in comparison with the control (table 3).

Table 3 Hematological parameters of mice with intramuscular administration of a complex of vitamins (n = 6, P> 0.05) Indicator Units rev. 1 group 2 group 3 group 4 group M m M m M m M m WBC white blood cells × 10 ^{9 / L} 6.4 2.28 5.9 2.40 6.6 1.87 6.6 1.44 absolute lymphocyte count LYM × 10 ^{9 / L} 4.7 2.49 four 1,50 4,5 0.98 3,1 1,11 absolute content of a mixture of monocytes, basophils and eosinophils MID × 10 ^{9 / L} 1,1 0.15 1,2 0.83 1,2 0.14 2,3 0.33 absolute granulocyte count GRA × 10 ^{9 / L} 0.6 0.21 0.7 0.61 0.9 0.12 1,2 0.26 relative lymphocyte count % 72.5 5.23 68,4 5.41 68 4.86 46.3 3.76 Lym relative content of a mixture of monocytes, basophils and eosinophils MID % 17.4 3.45 twenty 1.28 18,4 2,8 34,4 1.13 relative granulocyte count GRA % 10.1 1.31 11.6 2.82 13.6 1.98 19.3 3.08 erythrocytes RBC × 10 ^{12 / L} 8.98 1.24 9.1 1,11 9.82 0.98 8.94 0.72 Hb hemoglobin g / L 139 13.04 140 14.03 142 8.98 116 6.78 average concentration erythrocyte ICS g / L 299 4.87 305 6.46 305 8.56 304 9.36 average hemoglobin volume in one erythrocyte MSN Pg 15,5 1.10 15.4 1.14 14.5 1.68 13 0.98 mean red blood cell count MCV Fl 51.8 2.49 50,4 4.82 47.3 3.01 42.6 2.45 distribution width red blood cells by volume RDW-CV % 18.7 3.76 17.1 3.18 eighteen 1.86 14.8 0.10 relates. distribution width red blood cells by volume RDW-SD F1 48.3 6.40 43.1 4.41 42.7 4.3 31.5 7.70 hematocrit HCT % 46.5 5.80 45.9 6.02 46.5 5.08 38.1 1.09 platelets PLT × 10 ^{9 / L} 1118 102.24 1089 151.57 782 68,42 1209 74.30 mean platelet volume MPV F1 5.5 0.15 5.5 0.10 5.3 0.1 5.1 0.40 Relative width platelet volume by PDW F1 5.1 0.61 5,6 0.68 5.9 0.12 6.1 0.59 PCT thrombocrit % 0.616 0.06 0.601 0.09 0.413 0.08 0.621 0.04 large platelet ratio
P-LCR % 9.9 0.31 8.7 0.49 3.2 0.14 2.1 0.16

When pathomorphological examination of the internal organs of mice treated with the claimed drug, no pathological changes were noted.

Example 3

The claimed drug was tested in 2 groups of repair young birds of the cross "Rodonit-2". Groups of 200 goals were formed on the basis of analogues. The conditions for keeping the birds were the same. Both groups received a single diet, the composition of which complies with the recommendations of VNITIP.

Histological studies showed that in chickens receiving this vitamin-mineral complex from the first day, the volume of lymphatic follicles exceeded that in control chickens 2.5-3.5 times, which indicates an increase in the bird's immune status, activation of immunological centers - lymphofollicles , and also contributes to the growth of resistance to various pathogens of infectious diseases.

An analysis of the organs of birds was carried out, eggs from hen laying hens who systematically received the drug in the indicated doses were also examined for the content of selenium. The analysis results showed that the content of selenium in the liver, muscles, and also in eggs in the birds of the experimental group is 2-2.5 times higher than the content of selenium in the liver, muscles, and also in eggs in birds that received standard foreign premixes using selenite sodium.

According to the results of studies, it was found that feeding the proposed drug to hens of the experimental group had a positive effect on egg production and a longer peak in productivity. So, the intensity of the egg laying of 75 and 95% of the control hens showed on average 2 days earlier than the laying hens of the experimental group. Moreover, the egg laying intensity at the level of 94-99% of the laying hen of the experimental group was kept on average for 6 days longer than the laying hens of the control group. Over the entire period, the average egg production of hens in the experiment was 89.54% versus 84.89% in the control.

The use of the claimed drug had a positive effect on safety. In the control group, the mortality rate was 10.74, and in the experimental group - 6.28%. All this has the best effect on the productivity of chickens. During the study period, the gross egg yield in the experimental group was 9.28%, and the egg production was 8.18 more compared to the control. According to the egg production index, taking into account live weight, daily feed intake and the level of egg laying, laying hens of the experimental group were 7.34% higher than the control. The conversion of feed for chickens during the productive period also increased. So, for the formation of 10 eggs, the bird of the control group spent 5.38% more feed than the experimental one.

Assessment of the incubation quality of eggs of hens, which were added to the claimed drug, and without it was carried out at 26, 44 and 56 weeks of age. Both in morphological and biochemical parameters that contribute to satisfying the needs of the embryo and improving the hatchability of eggs, the hens of the experimental group exceeded the hens of the control group.

The grade of eggs of the experimental group also improved. Their eggs are characterized by significantly greater mass and density. In the yolk, as in the protein part of the eggs of experimental chickens, there is an increased content of protein, fat, carbohydrates with a constant level of ash. In addition, carotenoids, vitamins A, C and selenium were significantly more deposited in the yolk.

In the compared groups, the yield of eggs suitable for incubation increases with age, but at the same time in laying hens receiving mixed feed with the addition of the claimed preparation, this indicator is 0.9-4% higher in all age periods.

The hens of the experimental group significantly exceeded the hens of the control group in terms of fertility and hatchability.

According to the results of biological control carried out during the incubation process, the embryonic development of eggs from the hens of the experimental group was more intense than from the hens of the control group. The total incubation waste, namely: the level of blood cells in the yolk, the number of eggs with frozen embryos, the number of suffocates in the hens of the experimental group is on average 5% lower than in the hens of the control group, which contributed to an increase in the output of young animals.

The mass of organs involved in the body's immune defense (fabrika bag, spleen) in chickens of the experimental group is higher than in the control by 1.5 and 2 times, respectively.

It was also established that the use of the claimed medicinal product enhances the physiological activity and nutritional value of the liver, increases the content of vitamins and minerals in it, and reduces the accumulation of xenobiotics.

Poultry products after application of the claimed drug can be used without restrictions.

The above experimental data allow us to conclude that a harmless non-toxic vitamin-mineral complex has been obtained, which makes it possible to compensate for the deficiency of vitamins and selenium in the body of birds, and thereby increase its protective functions, which, in turn, makes it possible to effectively prevent and treat bird hypoavitaminosis under stress, with a decrease in productivity, with infectious and invasive diseases, with veterinary measures, as well as with low egg production and insufficient strength of the egg shell

In the claimed invention, the mutual influence of micronutrients is taken into account, their antioxidant activity is enhanced, which made it possible to obtain a drug of improved quality and to expand the range of domestic vitamin-mineral preparations for birds, i.e. solve the problem.

Claims (1)

A medicine for the prevention and treatment of hypoavitaminosis and normalization of metabolism in birds, containing vitamin A, vitamin D ₃ , vitamin E, a compound of selenium and targeted supplements, characterized in that it additionally contains vitamin C, and as a selenium compound contains DAFS-25 with the following ratio of ingredients in 1 liter of solution:
Vitamin A 25.0-35.0 ml Vitamin D ₃ 0.03-0.05 ml Vitamin E 55.0-65.0 g Vitamin C 90.0-110.0 g DAFS-25 0.2-0.4 g Polysorbate-80 190.0-210.0 ml 2-pyrrolidone 39.0-41.0 ml Distilled water to liter