Antianemic and growth-stimulating preparation

FIELD: pharmaceutics, veterinary science.

SUBSTANCE: the present innovation deals with preventing and treating hypomicroelementosis in different farm and domestic animals, furred animals, and, also, for enhancing the growth in animals, and treating a number of specific diseases and, also, for maintaining microelemental composition of feedstuffs. The suggested preparation includes chelated complex of iron, manganese, zinc, copper, cobalt, selenium and iodine with organic ligand of complexone type and water. According to the innovation as a chelation ligand it contains trisodium salt of methionine succinic (α-amino-γ-methylthiobutyric-N-succinic) acid at a certain ratio of components. The innovation provides to obtain preparation in soluble form being capable to be well digested by the animal.

EFFECT: higher efficiency.

 

The invention relates to animal breeding and fur farming, namely the drugs used in veterinary medicine for the prevention and treatment of element deficiency disease in various agricultural and domestic animals, fur-bearing animals, enhance the growth of animals, treatment of specific diseases, as well as to maintain the microelemental composition of the feed.

The main source of trace elements for animals are food. However, their mineral composition varies significantly and depends on many factors (soil, plant species, phases of the procurement, level of fertilization, climatic conditions etc). Often there is a lack of some elements and plenty of others. Minerals food absorbed by the body only 25-30%. Therefore, the problem of mineral nutrition of animals must be dealt with together, as by means of complete feed, and due to the introduction of trace element supplementation in the diet is not as feeding on each element separately, but as part of the complex elements. For the prevention and correction of disorders of metabolic processes apply additives to the diet of inorganic salts, trace elements. Meanwhile, inorganic salts, especially when clinical forms microelementoses, is not always sufficiently effective. This is due to their low bioavailability (about 20-30%), the result is E. what is the need for them in the body of animals is not satisfied even with adequate doses and prolonged use. At the same time, the bioavailability of many of the items above, if they are composed of organic compounds. In such compounds the activity of trace elements is greatly increased. Of particular interest are chelate compounds containing as a ligand a cyclic group, the so-called lesneven or chelate compounds. The use of chelate compounds provides a better assimilation of the metal than the introduction of it in the diet in inorganic or some other form. Such compounds are used inside and parenteral, they are able to pass through the placental barrier and exert a certain influence on the fetus, they have a positive effect on hematopoiesis, normalize metabolic processes.

Chelate complex compounds is most beneficial for the body form of interaction of the metal with the ligand.

Known synthetic methionine used in livestock for enrichment of diets (Wlkin. Feeding farm animals. M Spike. 1997. s-274). Methionine is an indispensable amino acids and is a critical amino acid in diets monogastric animals, birds, young ruminant animals, because these animals are unable to synthesize it from nitrogenous substances feed. Methionine is involved not only in protein synthesis, but is the integrated source metal groups, the synthesis of which in the body is limited. The most important methylation reactions proceeding involving methionine, are becoming guanidoacetic acid creatine, colamine in choline. The lack of synthesis of choline contributes to the violation of the transport of lipids from the liver into the blood. The absence or deficiency of methionine leads to a delay of animal growth and low feed conversion, often observed anemia, fatty liver, coarse and brittle hair, muscular atrophy. With the lack of methionine bind toxic dystrophy of the liver of pigs. In the practice of fur farming are mainly used bone by-products, protein which contains less than 30-60% of serosoderjaschei amino acids in comparison with protein muscle protein. These diets do not provide the body with essential amino acids, because the lack of methionine in the diet leads to deterioration of the quality of the skin by reducing the thickness of the hair layer, defects top coat.

Known Antianemic and growth-stimulating drug for animals, comprising a chelate complex of iron, manganese, zinc, copper, cobalt, selenium and iodine with an organic ligand, disodium or Pikalevo salt Ethylenediamine-N, N'-dinternal acid (EDAC) and water (RU # 2203657, class a 61 K 31/295, a 61 K 31/00, And 61 R 7/00, 2003).

The disadvantages of the known drug Rel what are some technological difficulties when it is received, associated with the use of volatile, highly toxic substances - Ethylenediamine, the production of which in Russia is missing, that makes use of the imported product. In addition, the drug is not effective enough.

Given the importance of methionine and trace elements in the life of the organism, it seems appropriate to introduce in animal feed methionine is not in the form of free amino acids and in the form of its compounds containing trace elements. However, such compounds are practically insoluble in water, which makes their application difficult and assimilation by the body of animals (V. Dorozhkin, Ph.D. dissertation, 1997).

The objective of the invention is to develop a new drug in a soluble form, can be well absorbed by the body, with the optimal ratio and a wide range of trace elements for the prevention and treatment of metabolic disorders and other diseases in agricultural and domestic animals, fur-bearing animals, birds, and the simplification of the production technology and exclusion from the production of highly toxic components.

The technical result of the invention is achieved by the fact that biogenic metals associated with organic ligand type complexone in an integrated connection chelate type, and the ligand is not only a carrier of biogenic metals, but is itself a metabolite and a stimulant metabolic processes./p>

This object is achieved in that in Antianemic and growth-promoting the drug for animals, comprising a chelate complex of iron, manganese, zinc, copper, cobalt, selenium and iodine with an organic ligand type complexone and water, according to the invention, as a ligand, it contains chinatravel salt methioninamide acid in the following ratio, wt.%:

trinacria salt

methioninamide acid 15,0-40,0

iron(III) 1,0-5,5

manganese(II) 0,25-3,0

copper(II) 0.1 to 0,55

zinc(II) 0,05-1,5

cobalt(II) 0,02-0,30

selenium(IV) 0,02-0,06

iodine(I) 0,01-0,08

water the rest.

In the inventive preparation methionine is the core of the molecule combined with the adjacent succinic acid. The resulting complexes chelated micronutrients type soluble in water and therefore well usvaivaetsya body. The drug is based on methioninamide acids and trace elements has immunomodulatory, stress-protective, growth and Antianemic action.

The ligand nationalenergy (α -aminoγ -meticiously-N-succinic acid obtained by the reaction of nucleophilic attachment of amines double bonds of unsaturated dicarboxylic acids.

Initially conduct a synthesis of the ligand by reacting equivalent quantities of sodium salts Mal is inovas acid and methionine at a temperature 105-107° C for 12-14 hours. Components used for the reaction, is not volatile and non-toxic, which simplifies the process of obtaining ligand and makes it safe.

Antianemic growth-promoting drug Gambit - Mean get in enameled reactor or in the reactor of stainless steel by interaction trinational salt methioninamide acid and salts of trace elements. As salts of trace elements you can use their chlorides or sulfates. You may also use them in the form of crystalline and anhydrous salts.

Example.

The reactor was loaded into the aqueous solution 313,6 kg (70,70% mass.) chinatravel salt methioninamide acid. In a separate reactor was obtained solutions of salts of iron (III), copper (II), manganese (II), zinc (II), cobalt (II) by dissolving 45 kg (10,15%) of softened water 46,5 kg (10,47%) FeCl3, 27,0 kg (6,09%) MnSO4×H2O 4.2 kg (0,95%) ZnCl2, 5,0 kg (1.13 per cent) CuSO4×5H2O, 1.2 kg (0,27%) Cl2×6H2O. the resulting solution of salts of trace elements is transferred to the reactor containing the ligand, and at a temperature of 70-80° is stirred for one hour.

A solution of compounds of iodine and selenium receive separately, dissolving 0.35 kg (0,08%) Na2SeO3and 0.3 kg (0,07%) Kl 0.4 kg (0,09%) of water and add to the total mass within 1 hour after administration of the other is microelemental at a temperature of 70° C and stirred for 5 minutes.

Upon receipt of a complex of trace elements and methioninamide acid, changing the number of individual trace elements, it is possible to obtain a product containing necessary for each case the ratio of trace elements. When receiving the drug quantity methioninamide acid must be greater than the total number of all micronutrients 0.5 to 3.0%.

The resulting product is a dark brown liquid (pH aqueous 6-8, mass fraction of iron is 3.5%). The drug is infinitely soluble in water and insoluble in organic solvents. The solution should be stored in glass or plastic containers. Store in containers made of ferrous metals or aluminum is unacceptable due to the corrosive activity of the drug.

Distillation of water at a temperature 108-110° you can obtain the product in paste form. For example, having driven from the resulting solution and 120 l of water, get a paste-like substance of a dark brown colour, pH of a 10%aqueous solution of 6-8, the mass fraction of iron 4,80%. Upon receipt of the preparation in paste form solutions of iodine compounds (I) and selenium(IV) is added to the reaction mass after the distillation of a given quantity of water, cooled the reaction mass to 75-80° C. After cooling to room temperature, the product turns into Pasto is brazee substance. Keep it in an airtight container, because it is hygroscopic.

Studies to determine the acute and sub-chronic toxicity of the preparation was carried out according to the “guidance on determining the toxic properties of drugs used in veterinary medicine and animal husbandry (extract from the normative documents approved by the USSR Ministry of health, agricultural Sciences, BS Gosagroprom USSR), Handbook of Veterinary drugs”, 1988.

Acute experiments on mice allowed us to determine that the drug is HOST to hazard class 4 (slightly hazardous), and the calculated ratio of cumulation showed no cumulative properties.

Efficacy of the drug Gambit - Mean can be illustrated by the following examples.

Example 1.

The biological activity of the drug Gambit - Mean evaluated on the model reproduced experimentally posthemorrhagic anemia white rats. There were formed two groups of rats 10 goals each. The first group in the month received, in addition to diet drug Gambit - Mean based on trace elements, mg/kg BW: Fe-2,0; Mn-1,0; Zn-0,2; Cu-0,2; Co-0,03; Se-0,02; I-0,025. The second group received only diet and served as control.

As before the experiment, all rats for seven days received the same General diet, preveden the e background figures are average figures and reflect the physiological condition of the animals in both groups.

The daily medication was administered to the experimental group in the form of a solution in distilled water using a probe, because there was no guarantee that feed it rats will be eaten completely. Weighing in rats was conducted at the beginning of the experiment and after 30 days of experience.

Hematological parameters were determined in the dynamics at the beginning of the experience; then after 15 and 30 days of experience. All animals were collected from tail vein blood was determined the content of total protein, hemoglobin, erythrocytes, hematocrit. The results obtained are presented in table 1.

From table 1 it is evident that the drug Gambit - Mean has a positive effect on hemo - and erythropoiesis. In rats receiving the drug, to 15-20 day experience gradually disappeared clinical signs of anemia.

Table 1 also shows that before the beginning of the experiment, the animals were also registered a lower level indicators red blood. In the experimental group they are normalized. Drug Gambit - Mean and activates the metabolism, as evidenced by increased levels of total protein in the blood of rats from the experimental group and the nature of changes in body weight of animals experimental and control groups.

Example 2.

To determine therapeutic efficacy of the drug Gambit - Mean with malnutrition was formed three groups of pigs lipotropics months of age on 9 goals each./p>

The first group received in addition to diet drug Gambit - Mean during the month based on trace elements, mg/kg masses: Fe-3,0; MP-1,5; Zn-2,0; Cu-0,3; Co-0,03; Se-0,02; I-0,025. The second group received the trace elements in the composition of the drug Gambit - plus in the form of a complex with ethylenediaminetetra acid in the same dosage for trace elements. The third group of pigs served as control and received only General ration.

The drugs were diluted with water 5 times and thoroughly mixed with the feed. The results of the experiment are shown in table 2.

The data of table 2 show that both microelement drugs are quite effective in the treatment of malnourished piglets. To experience the morphological and biochemical parameters in piglets of lipotropics were below the physiological norm. Trace element preparations contribute to the restoration indicators hemo - and erythropoiesis, total protein and nonspecific resistance. Drugs consistently provided average daily weight gain of animals. In the first and second groups with the average increase amounted to 241 and 227 g against 198 g in control. Table 2 also shows that the drug Gambit - Mean has a slight advantage over Semovita - plus, which can be explained by the increased activity of the ligand associated with the inclusion in the composition of the ligand mation is a, critical amino acids.

Because of the natural resistance of animals is a function of the immune system, to increase the bactericidal and lysozyme activity of blood serum can be judged as immunostimulating activity of drugs, and about the improvement of the activity of the immune system.

Analyzing the results of the determination of bactericidal activity of blood serum as an integral factor of nonspecific humoral defenses, reflecting mainly the immune status of animals, it can be noted that in animals of the first group, this rate was higher than in the control 18%, and was slightly higher than in the second group. Another indicator, namely lysozyme as an inducer of macrophage functions of the body from lipotropics plays an important role in humoral defense of the organism. Lysozyme activity in the first group increased by 14.9% compared with the control was higher than in the second group.

It was thus established that the drug Gambit - Mean promotes healing of animals, increases weight gain, restores morphological indicators hemo - and erythropoiesis, stimulates nonspecific resistance.

Example 3.

Research on the effectiveness of drug Gambit - Mean was conducted on the downhole young Minks pastelovej color. Was is lobrano 220 heads puppies males, divided into 2 groups by 110 heads.

Experimental group received trace elements associated with methioninamide acid Gambit - Mean from calculation of a daily dose of mg/head: Fe-2,0; MP-1,0; Zn-0,3; Cu-0,2; Co-0,05; Se-0,02; I-0,025.

The control group received the same daily dose of micronutrients, but associated with ethylenediaminetetra acid (Gambit - plus). In the rest of the conditions and feeding of both groups were identical.

Daily observation of animals deviations in their behavior is not observed, the experimental mink were clinically healthy, well-eaten food; animal waste was not observed. During the experiment was monitored blood counts, change in body weight; after slaughter was conducted by the Commission assessment of the quality of the skins. The results of the experiment are presented in tables.

15,80±0,13
Table 3
The hemoglobin content in the blood of young mink, g%
GroupDetermination date
15.0616.0715.0815.09 
Experienced14,85±0,1415,88±0,1217,14±0,1617,97±0,0818,17±0,09
Control14,91±0,11equal to 16.83±0,0917,45±0,1017,84±0,08

Table 4
The content of total protein in the serum of young mink, g%
GroupDetermination date
15.0815.0915.10
Experienced7,52± 0,037,84± 0,048,18± 0,05
Control7,50± 0,027,72±0,05to $ 7.91±0,04

Table 5
Speaker body weight (g) experimental young mink
GroupDate weighting
15.0616.0715.0815.0915.10
Experienced810,4±7,31319,7±9,61709,3±12,42024,1±13,42154,3±16,1
Control812,b±8,21285,6±11,41690,1±10,21979,6±14,22079,4±13,1

As can be seen from the presented results, the experimental animals during the whole experience, the hemoglobin level was higher. The content of total protein in serum mink experimental group was also higher than animals in the control group. This indicator is one of the characteristics of metabolic processes in the organism and the nature of its changes in animals experimental and control groups is consistent with the change of body weight. The live weight of the experimental group at the bottom was more by 3.6%than in the control.

Under the Commission assessing the quality of the skins, it was noted that some animals of the control group density of hair, especially on the flanks, was somewhat lower than in the experimental animals. In the experimental group were marked lengthening of the spine and it is uniform in length and thickness. Animals of the control group met the splitting of the peaks of the guard hairs. These phenomena can be caused by lack of methionine in the diet.

Thus, the drug Gambit - Mean stimulates hemopoiesis; intensifies the growth of young animals, improves the quality of fur products.

Example 4.

Efficacy of the drug Gambit - Mean has been studied in calves. The test was carried out on 30 calves black-motley breed at the age of 7-10 days, divided into experimental and control group on 15th goal of the century The number of steers and heifers in groups was the same. Conditions and diets of the animals in both groups are identical. Calves from the experimental group received in addition to diet drug Gambit - Mean based on trace elements per head per day, mg: Fe-100,0; Mn-50,0; Zn-60,0; si-10,0; Co-2,0; Se-1,0; I-1,5. The preparation was given individually for each animal.

The results of the experiment are shown in table 7.

From the presented data it follows that the use of the drug Gambit - Mean stimulate hematopoiesis. In the experimental group this indicator at the end of the experience comes close to the upper limit of the physiological norm, while in the control it tends to lower limit of the norm. A similar change in the level of total protein in serum. The drug intensifies protein metabolism in the body, which has a positive impact on the increase in live weight. The live weight of animals of the experimental group was towards the end of the experience more than 14.8%, than in control. Average daily gain was 0.69 kg in the experimental and 0.45 kg in the control groups.

Thus, the drug Gambit - Mean simulates haematopoiesis; has a positive effect on the increase in live weight of the animals.

Example 5.

The influence of the drug Gambit - Mean on the productivity of laying hens of cross Lowenbraun at the age of 65 weeks. To the diet of chickens experienced group is s (9800 heads) was added drug Gambit - Mean based on trace elements in 1 kg of feed, mg: Fe-10,0; Mn-40,0; Zn-10,0; Cu-1,0; Co-0,1; Se-0,1; I-0,12. In the rest of the conditions and feeding experimental (9800 heads) and control( 10200 heads) groups were the same.

At the beginning of the experience productivity in both groups was $ 61.3%. It is noted that 15 days after the start of the experiment, the productivity in the experimental group reached 65.4%and in control group it was 59.2%, which is associated with a characteristic age-related decline in productivity. Mortality of birds in the experimental group was 3.5% less than in control. Drug Gambit - Mean increases the productivity of laying hens, extends the productive period, increases the safety of the birds.

Thus, it was found that trace the growth-promoting drug Gambit - Mean stimulates blood and erythropoiesis, has a positive effect on metabolic processes, increases the nonspecific resistance of the organism. The drug stimulates the growth, development and productivity of animals, improves the quality fur products, fur-bearing animals. Especially important is the inclusion of the drug in the diet of young cattle, monogastric animals, birds, whose bodies are unable to synthesize essential amino acids, including methionine.

Currently, studies of the drug “Gambit - Mean” on animals and is preparing its production in OOO “Gambit” , TV is R.

Antianemic and growth-stimulating drug for animals, comprising a chelate complex of iron, manganese, zinc, copper, cobalt, selenium and iodine with an organic ligand type complexone and water, characterized in that, as a ligand, it contains chinatravel salt methioninamide (α-aminoγ-methylthiophenol-N-succinic) acid in the following ratio, wt.%:

Trinacria salt methioninamide 15,0-40,0

acid

Iron(III) 1,0-5,5

Manganese(II) 0,25-3,0

Copper(I) 0.1 to 0,55

Zinc(II) 0.1 to 0,55

Cobalt(II) 0,02-0,30

Selenium(IV) 0,02-0,06

Iodine(I) 0,01-0,08

Water the Rest



 

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