RU2277800C1 - Microelement preparation for animals - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: composition comprises in % by mass: 2Na- or 2K-salt of ethylene diamine-N,N¹-disuccinic acid 15.0-35.0; Na- or K-salt of amino acid 2.0-10.0; salts of iron (III) 0.6-3.0; manganese (II) 0.5-2.5; copper (II) 0.05-0.25; zinc (II) 0.3-2.5; cobalt (II) 0.005-0.05; selenium (IV) 0.01-0.03; iodine (I) 0.03-0.08; water takes the rest. Amino acid is selected from group containing glycine, alanine, valine, aspartic acid, glutamic acid, lysine, methionine, cystine, threonine and tryptophan.

EFFECT: eliminated microelement deficiency; stimulated erythropoiesis and nonspecific organism resistance.

2 cl, 10 tbl

Description

The invention relates to animal husbandry and veterinary medicine and can be used for the prevention and treatment of iron deficiency anemia, metabolic disorders, enhance animal growth, treatment of a number of specific diseases.

Known anti-anemic and growth-promoting drug for animals - hemovit-plus (RU 2203657, 05/10/2003, Bull. No. 13, A 61 K 31/295). The preparation includes a complex of iron, manganese, cobalt, copper, zinc, selenium and iodine with disodium or dipotassium salt of ethylenediamine-N, N'-di-succinic acid in the following ratio, wt.%: Disodium or dipotassium salt of ethylene diamine-N, N'- disuccinic acid - 15-25; iron (III) 0.6-5.0; manganese (II) 0.5-2.0; copper (II) 0.05-0.25; zinc (II) 0.1-1.5; cobalt (II) 0.005-0.05; selenium (IV) 0.01-0.03; iodine (I) 0.01-0.05; water is the rest.

The drug eliminates the deficiency of microelements, stimulates erythropoiesis, increases the nonspecific resistance of the body, and prevents white muscle disease, endemic goiter. The use of the drug enhances reproductive ability, stimulates the growth, development and productivity of farm and domestic animals.

However, in some cases, the drug is not effective enough when used and the introduction of a number of additional components of a protein nature is required to stimulate the growth of animals and normalize metabolism, since this drug contains only the trace element of the feed.

The objective of the invention is to increase the effectiveness of the drug with optimal ratios of trace elements and amino acids for the prevention and treatment of metabolic disorders in farm and domestic animals.

To solve this problem, a preparation based on the 2Na- or 2K salt of ethylenediamine-N, N ¹ -disuccinic acid and a salt of iron, manganese, copper, zinc, cobalt, selenium and iodine additionally contains a Na- or K-salt of an amino acid selected from the group : glycine, alanine, valine, aspartic acid, glutamic acid, lysine, methionine, cystine, threonine, tryptophan, in the following ratio of ingredients, wt.%:

2Na- or 2K salt of ethylenediamine-N, N ¹ -disuccinic acid 15.0-35.0; Na- or K-salt of amino acids 2.0-10.0; iron (III) 0.6-3.0; manganese (II) 0.5-2.5; copper (II) 0.05-0.25; zinc (II) 0.3-2.5; cobalt (II) 0.005-0.05; selenium (IV) 0.01-0.03; iodine (I) 0.03-0.08; water the rest.

As a salt of iron (III), manganese (II), copper (II), zinc (II), cobalt (II), the preparation contains their inorganic salts, such as sulfates or chlorides in the form of hydrates or anhydrous salts. As a salt of selenium (IV), the preparation contains sodium selenous acid, and as a salt of iodine (I) - potassium or sodium iodide.

As an amino acid, the preparation contains a Na- or K-salt of an amino acid of the general formula R- (NH ₂ ) COOH containing an amino group in the α-position to the carboxyl group. As these compounds, monoaminocarboxylic acids (glycine, alanine, valine), monoaminodicarboxylic acids (aspartic, glutamic), diaminomonocarboxylic acid (lysine), thioamino acids (methionine, cystine), hydroxy amino acid (threonine), and heterocyclic amino acid can be used.

Thus, the proposed composition (chelavit preparation) is a biligand complex of a succinic acid derivative forming 2 five-membered chelate rings with a metal ion and an amino acid (including irreplaceable) containing an amino group in the α-position to the carboxyl group and also forming a five-membered chelate cycle with metal ions. The use of two ligands with different molecular weights, used as transport molecules for the delivery of trace elements across the cell membrane, can increase the bioavailability of trace elements and the effectiveness of the drug compared with the use of inorganic salts.

An additional introduction to the system of a complex of trace elements with an amino acid increases the intake of additional nutrients into the body to enhance the growth and development of animals. In general, this composition allows you to normalize the metabolism and strengthen erythropoiesis.

The introduction of an amino acid salt of less than 2.0 wt.% In the composition does not significantly increase the effectiveness of the drug. The introduction of more than 10 wt.% Increases the cost of the drug.

According to the invention, the chelavit preparation is prepared by reacting an alkaline solution of the 2N- or 2K salt of ethylenediamine-N, N'-di-succinic acid and the Na or K salt of an amino acid at a pH of 11-13 and a temperature of 60-70 ° C with the calculated amount of iron salts ( III), manganese (II), copper (II), cobalt (II), zinc (II), selenium (IV), iodine (I). The resulting preparation is a dark brown liquid (pH 6-8). The resulting compound is unlimitedly soluble in water and not soluble in organic solvents. The solution of the drug should be stored in a glass or plastic container. The composition obtained in the form of a paste or powder by evaporation of water is hygroscopic.

Acute and subchronic toxicity of the drug was carried out according to the "Methodological guidelines for determining the toxic properties of drugs used in veterinary medicine and animal husbandry" on white mice and rats. According to the results of the experiments, the value of LD ₅₀ according to Kerber was calculated, which amounted to more than 20,000 mg / kg of live weight, which according to GOST 12.1.007.76 classifies the drug as a hazard class 4 (slightly hazardous).

The effectiveness of the drug can be illustrated by the following examples.

Example 1. 2 groups of puppies of 6 months of age were formed from two litters of the same constitution and weight according to the pair-analogue method. Throughout the experiment, the experimental and control groups were fed the same diet, the control group received an additional hemovit plus drug (prototype), and the experimental group received the proposed chelavit preparation containing a biligand complex of trace elements of the following composition, wt.%: 2Na-salt of ethylenediamine-N, N'-disuccinic acid 15.0; Na salt of methionine 4.0; iron (III) 3.0; manganese (II) 1.0; copper (II) 0.15; zinc (II) 0.5; cobalt (II) 0.05; selenium (IV) 0.03; iodine (I) 0.05, water - the rest. Dosages for iron of the drug Helavit and prototype - 1.0 mg per 1 kg of live weight. Clinical, biochemical and immunological studies of animal blood were carried out. Sampling was carried out at the beginning of the experiment, 10, 20 and 40 days of the experiment.

Data on clinical indicators are given in table 1.

Table 1 Clinical indicators of blood puppies Group Days 0 10 twenty 40 65 White blood cells × 10 ³ / μl Experience 7.04 ± 0.06 7.3 ± 0.068 9.4 ± 0.25 12.5 ± 0.15 11.43 ± 0.12 Control 7.02 ± 0.06 7.19 ± 0.05 7.56 ± 0.08 8.19 ± 0.1 7.77 ± 0.09 Red blood cells, × 10 ⁶ / μl Experience 4.35 ± 0.11 5.48 ± 0.12 5.80 ± 0.13 6.00 ± 0.09 6.57 ± 0.09 Control 4.37 ± 0.1 6.16 ± 0.09 6.60 ± 0.11 7.21 ± 0.12 6.70 ± 0.09 Hemoglobin, g / l Experience 91.8 ± 1.46 116.8 ± 1.59 143.4 ± 1.31 163.1 ± 2.41 137.4 ± 2.2 Control 92.3 ± 1.33 108.3 ± 1.91 115.2 ± 1.31 127.7 ± 1.37 114.8 ± 1.42

As can be seen from the data in Table 1, starting from the 10th day, in the experimental group there was a significant increase in all three hematological parameters in relation to the experimental period, and an increase in the amount of hemoglobin in relation to the control was also noted.

The greatest difference in indicators between the groups is observed on the 40th day, that is, at the time of the last day of the use of the drug and is an excess of 28.3% in the group of controls over the hemoglobin control group and 52.6% in leukocytes. In the content of red blood cells, the opposite tendency was observed and the excess of this indicator was 16.6% in the control group.

The data in the table indicate the best positive dynamics of hematological parameters in the experimental group. It should also be noted a greater saturation of red blood cells with hemoglobin in animals of the experimental group.

Data on the content of total protein and protein fractions in the blood serum of puppies are presented in tables 2 and 3.

table 2 Total protein, g / l Group Days 0 10 twenty 40 65 Experience 59.1 ± 1.1 67.0 ± 0.84 72.8 ± 1.45 75.7 ± 0.97 58.6 ± 1.1 Control 58.6 + 1.06 63.7 ± 1.07 65.2 ± 0.94 68.2 ± 0.07 59.0 ± 1.18

From the presented data it follows that the proposed composition has a pronounced effect on protein metabolism. The excess of the experimental group data: the amount of total serum protein by 11% (day 40), the albumin fraction - 9.3% (day 10), the globulin fraction 16.9% (day 40).

Table 3 Protein fractions Group Days 0 10 twenty 40 65 Albumin, g / l Experience 26.19 ± 0.68 30.26 ± 0.57 30.41 ± 1.0 30.80 + 0.72 28.28 ± 0.9 Control 25.78 ± 0.58 27.69 ± 0.65 28.87 ± 0.48 30.63 ± 0.57 28.2b ± 0.79 Globulins, g / l Experience 32.91 ± 0.7 36.54 ± 0.6 42.29 ± 1.05 43.92 ± 0.78 30.32 ± 0.56 Control 32.82 ± 0.73 37.01 ± 0.83 36.83 ± 0.69 37.57 ± 0.72 30.74 ± 0.82

The increase in protein metabolism in the experimental group has a positive effect on the growth rate of animals (table 4).

Table 4 The dynamics of growth in live weight of puppies, kg Group (n = 10) Days 0 40 Experience 8.03 ± 0.18 12.35 ± 0.32 Control 7.96 ± 0.13 11.11 ± 0.38

The observed excess of the indicators of the experimental group over the control is 11.2%.

The change in the content of humoral factors of the puppies' natural resistance is presented in Table 5.

Table 5 Change in the content of humoral factors in the puppies' natural resistance Group Days 0 10 twenty 40 65 Lysozyme activity,% Experience 14.15 ± 0.5 16.83 ± 0.45 31.57 ± 1.65 24.23 ± 0.15 21.7 ± 0.47 Control 14.08 ± 0.49 15.8 ± 0.6 24.7 ± 0.74 18.9 ± 0.36 17.69 ± 093 Bactericidal activity of blood serum,% Experience 65.9 + 2.64 91.1 ± 1.43 84.9 ± 3.79 93.7 ± 1.1 80.2 ± 3.06 Control 68.0 ± 2.34 75.2 ± 1.78 79.1 ± 1.14 92.6 ± 1.58 70.3 ± 2.08

From the data of table 5 it follows that the proposed composition has a more pronounced effect on the immune reactivity of the body. The maximum excess of the indicator of bactericidal activity of blood serum is 21.1% (10th day), the indicator of lysozyme activity is 27.8% (20th day).

Example 2. The study of the effectiveness of the drug chelavit composition, wt.%: (2Na-salt of ethylenediamine-N, N'-disuccinic acid 20.0; Na-salt of glycine 8.0; iron (III) 0.6; manganese (II) 2.5; copper (II) 0.05; zinc (II) 2.5; cobalt (II) 0.03; selenium (IV) 0.02; iodine (I) 0.08, water - the rest), carried out on 20 calves of black-motley breed aged 5-10 days, divided into 2 groups of 10 goals (on the basis of analogues). Feeding and keeping animals of both groups was the same. The calves of the control group for 30 days in addition to the main diet received a daily hemovit-plus preparation (prototype) at the rate of 100 mg of iron per head, the experimental group received the proposed drug in the same dosage. Clinical indicators of animal blood are presented in table.6.

Table 6 Indicators of animal growth dynamics and clinical indicators of calf blood Group Wed live weight, kg The average daily gain, g Hemoglobin, g / l Red blood cells, × 10 ¹² / l Start end Start end Start end Experience 35.1 49.6 485 ± 25 83.4 ± 1.4 131 ± 9.1 4.9 ± 0.3 5.9 ± 0.9 Control 35.0 46.8 393 ± 40 83.2 ± 7.2 98 ± 9.2 4.8 ± 0.2 5.1 ± 0.8

The results of Table 6 indicate a more intense stimulation of erythropoiesis in animals of the experimental group treated with the Helavit drug, which will allow us to recommend the proposed drug as an antianemic and growth-stimulating agent in animal husbandry and veterinary medicine.

Example 3. Two groups of black-motley calves were formed, 20 animals each, of the same age. The control group received hemovit-plus, the experimental group received chelavit of the following composition, wt.%: 2Na-salt of ethylenediamine-N, N ¹ -disuccinic acid 35.0; Glutamic acid Na-salt 2.0; iron (III) 1.5; Manganese (II) 1.5; copper (II) 0.2; zinc (II) 1.5; cobalt (II) 0.005; selenium (IV) 0.01; iodine (I) 0.03, water - the rest. Dosages of both drugs for iron - 100 mg per head per day. Clinical blood counts of calves and weight gain data 30 days after the start of drug administration are given in Table 7.

Table 7 Clinical blood counts of calves and weight gain data Indicators Groups control experienced Hemoglobin, g / l 105 116 Red blood cells, 10 ¹² / l 5.9 6.17 White blood cells, 10 ⁹ / L 7.0 7.4 The average daily gain in live weight, g 510 570

From the data of Table 7 it follows that in the group of calves treated with the drug, clinical blood counts improved and the average daily weight gain of animals increased from 510 g (control) to 570 g (experience).

Example 4. The effectiveness of the proposed drug helavit was carried out on dairy cows of the Yaroslavl breed. Groups of 10 goals were formed by the method of pair-analogues. The control group received the prototype drug, and the experimental group received helavit in a dosage of 200 mg of iron per head per day. The following chelavit preparation was used, wt.%: 2K-salt of ethylenediamine-N, N'-di-succinic acid 25.0; Alanine K-salt 5.0; iron (III) 1.7; manganese (II) 1.2; copper (II) 0.17; zinc (II) 1.5; cobalt (II) 0.02; selenium (IV) 0.017; iodine (I) 0.05, water - the rest. Biochemical parameters of blood serum after 20 days are shown in table.8.

Table 8 Biochemical indicators of blood serum of cows Indicators Groups control experienced AST, E / l 82.26 72.05 Alt, E / L 36.34 30.73 Alkaline phosphatase, E / l 112.0 76,2

As follows from the data of Table 8, in animals of the experimental group, a decrease in the activity of enzymes in the blood serum was observed, which indicates the normalization of calcium metabolism in animals and an improvement in the physiological state of the liver.

Example 5. Two groups of dog puppies were formed, 1 year old with 5 animals each. The control group received, in addition to the diet, a hemovit-plus preparation, and the experimental group received helavit in a dose of 0.5 mg of iron per 1 kg of live weight per day. The composition of the drug chelavit, wt.%: 2Na-salt of ethylenediamine-N, N'-di-succinic acid 20.0; Tryptophan Na-salt 10.0; iron (III) 1.7; manganese (II) 0.9; copper (II) 0.18; zinc (II) 0.34; cobalt (II) 0.035; selenium (IV) 0.015; iodine (I) 0.04, water - the rest. After 30 days, the clinical blood counts were determined in animals of both groups. The data are given in table.9.

Table 9 Clinical blood counts of puppy dogs Indicators Groups control experienced Hemoglobin, g / l 145.6 152.3 Red blood cells, 10 ¹² / l 5,6 5.9 White blood cells, 10 ⁹ / L 9.8 10.5

As follows from the data in Table 9, there is an improvement in the clinical blood parameters of the puppies' blood dogs of the experimental group, which indicates a greater effectiveness of the proposed drug in comparison with the analogue.

Example 6. Six dog groups were formed with 5 animals each. The control group received hemovit-plus in addition to the diet, and the experimental groups (1-5) received helavit at a dose of 0.5 mg of iron per 1 kg of live weight per day. The drug Helavit additionally contains amino acids: group 1 (Na-salt of valine); group 2 (Na salt of aspartic acid); group 3 (K-salt of cystine); group 4 (K-salt of threonine); group 5 (Na salt of lysine) in an amount of 2.0-10.0 wt.%. After 30 days, the clinical blood counts were determined in animals of both groups. The data are given in table 10.

Table 10 Clinical blood counts of dogs Indicator Groups control experienced one 2 3 four 5 Hemoglobin, g / l 145.6 152.6 153.3 150.8 156.4 158.1 White blood cells, 10 ⁹ / L 9.8 10.3 10.5 10.1 10.7 10.9 Red blood cells, 10 ¹² / l 5,6 5.7 5.7 5,6 5.7 5.9

As follows from the data of table 10, there is an improvement in the clinical blood parameters of dogs of the experimental groups, which also confirms the greater effectiveness of the proposed compositions in comparison with the analogue.

Thus, the data presented in tables 1-10 indicate the high efficiency of the proposed biligand composition with 7 trace elements. Since micronutrients are linked into a stable chelate complex with ligands, this composition does not destroy vitamins, metal ions are in a stable state and do not undergo hydrolysis.

The composition of the composition of the complex of amino acids with metal ions allows the body to provide essential amino acids, which increases the value of the proposed composition.

The proposed composition can also be used as an immunomodulator, as it enhances the general non-specific resistance of the animal organism and normalizes metabolism.

Claims (2)

1. A microelement preparation for animals containing a 2Na- or 2K salt of ethylenediamine-N, N ¹ -disuccinic acid and a salt of iron, manganese, copper, zinc, cobalt, selenium and iodine, characterized in that it additionally contains Na- or K the salt of an amino acid selected from the group of glycine, alanine, valine, aspartic acid, glutamic acid, lysine, methionine, cystine, threonine, tryptophan, in the following ratio of ingredients, wt.%: 2Na- or 2K salt ethylenediamine-N, N ¹ -disuccinic acid 15.0-35.0 Na- or K-salt of amino acids 2.0-10.0 Iron (III) 0.6-3.0 Manganese (II) 0.5-2.5 Copper (II) 0.05-0.25 Zinc (II) 0.3-2.5 Cobalt (II) 0.005-0.05 Selenium (IV) 0.01-0.03 Iodine (I) 0.03-0.08 2. The microelement preparation for animals according to claim 1, characterized in that it contains their chlorides or sulfates as salts of iron, manganese, copper, zinc, cobalt, contains selenic acid sodium, and contains iodine salt potassium or sodium iodide.