RU2774429C1 - Biologically active food or feed additive - Google Patents

Abstract

FIELD: biologically active additives.

SUBSTANCE: invention relates to biologically active additives (BAA) for food and feed purposes, containing vitamins, amino acids and trace elements, as well as to the field of medical and veterinary pharmacology. The dietary supplement contains vitamins A, B₁, B₂, B₅, D₃ and E, zinc, manganese in the form of their complexes with ethylenediaminetetraacetic acid (EDTA), selenium. At the same time, the dietary supplement contains amino acids in the form of an enzymatic hydrolyzate of vegetable protein with a degree of cleavage equal to 35-45%, iodine in the form of 3,5-diiodine-L-tyrosine, and additionally contains vitamins B₆ and PP and water with the following amounts of components per 1 liter of supplement: vitamin A - 500000-18000000 IU, vitamin B₁ - 0.5-5.0 g, vitamin B₂ - 0.5-10 g, vitamin B₅ - 4.0-17.0 g, vitamin B₆ - 0.2-3.0 g, vitamin D₃ - 490000-5000000 IU, vitamin E - 1.0-9.0 g, vitamin PP - 2.0- 20.0 g, zinc - 0.5-1.5 g, manganese - 0.5-1.5 g, amino acids in the form of enzymatic hydrolyzate of vegetable protein - 100.0-300.0 g, selenium - 0.025-0, 09 g, iodine - 0.05-0.5 g, water - up to 1 liter.

EFFECT: invention makes it possible to obtain dietary supplements with high biological activity and complex stimulating effect.

1 cl,1 tbl

Description

The invention relates to biologically active additives for food and feed purposes, containing vitamins, amino acids and trace elements, as well as to the field of medical and veterinary pharmacology.

Growth processes, the level of productivity and the state of health of farm animals and poultry depend on a number of internal and external conditions, among which the intake of amino acids, vitamins and microelements into the body of animals and birds is of no small importance.

Insufficient intake of certain vitamins, amino acids and microelements into the body of animals and poultry can significantly retard their growth, cause pathology and reduce productivity.

In addition, young animals, due to the high intensity of growth, need relatively more vitamins, amino acids and trace elements than adult animals.

To ensure a full rational nutrition of farm animals and poultry and adequate animal husbandry, it is necessary to use complex preparations and feed additives containing substances vital for animal health.

As a dietary supplement, the invention stimulates human immunity, compensates for microelement deficiency, prevents the development of alimentary iodine deficiency (registered in 2 billion people on the planet), the consequence of which is considered to be such pathological conditions as endemic goiter (740 million patients), endemic congenital cretinism (6 million), mental retardation (43 million), hypothyroidism (100 million), myxedema, Graves' disease, etc.

Also dietary supplement eliminates the development of pathologies (polyneuritis, pink disease, scurvy and rickets) associated with a lack of vitamins in the human body.

The peptides contained in dietary supplements have a quick restorative effect after heavy human loads, as a result, athletes, when using dietary supplements, improve such indicators as strength, endurance, coordination and speed.

There are drugs on the market that contain a complex of vitamins, amino acids and microelements, such as Chiktonik, Gammatonik, Aminovital, Nutril Se, Hydro Rex Vital Amino Acids, Extravital.

Closest to the proposed is a premix for farm animals and poultry containing salts of trace elements, succinic acid, ascorbic acid, citric acid mycelium, defluorinated phosphate, lysine, methionine, as well as vitamins and wheat bran in the following ratio, wt.%:

Mycelium of citric acid - 50.0-76.2

Iron citrate - 0.1-0.5

Zinc citrate - 0.13-1.2

Manganese citrate - 0.3-0.8

Copper citrate - 0.01-0.4

Cobalt citrate - 0.01-0.025

Potassium iodide - 0.007-0.02

Sodium selenite - 0.002-0.005

Succinic acid - 0.015-0.04

Lysine-0.3-1.0

Methionine - 0.15-0.5

Defluorinated phosphate -1.0-2.0

Vitamins:

A - 0.05-0.4

D ₃ - 0.01-0.05

E - 0.02-0.15

B ₁ - 0.01-0.035

B ₂ - 0.015-0.05

B ₃ - 0.04-0.1

B ₄ - 4.0-7.5

B ₅ - 0.15-0.26

At ₁₂ - 0.00015-0.0005

Ascorbic acid - 0.25-0.5

Wheat bran - the rest (RU 2156080 C1, publ. 20.09.2000).

The disadvantage of the known premix is the presence of trace elements, including iodine and selenium, in the form of inorganic compounds.

This premix is a mixture of water-soluble inorganic compounds of iodine (iodide or, more rarely, potassium iodate) and selenium. This combination is used because of the simplicity and cheapness of preparation. However, its serious shortcomings are well known - a relatively high toxicity (LD50 for selenium compounds - 4-5 mg / kg, for iodine compounds - 60-100 mg / kg) and, most importantly, chemical instability and a tendency to secondary pharmacokinetic and pharmacodynamic interactions with other inorganic components of the atmosphere, water, food or semi-finished food.

And the oxidation of the iodide ion with air oxygen, followed by the loss of volatile molecular iodine, is the reason for the short shelf life of the iodine-containing premix.

The technical problem solved by the invention is the production of a biologically active food or feed additive with high biological activity and a complex stimulating effect.

The technical problem is solved by a dietary supplement containing vitamins A, B_one, B₂, B₅(calcium pantothenate), D₃ and E, amino acids in the form of an enzymatic hydrolyzate of vegetable protein with a degree of cleavage equal to 35-45%, iodine in the form of 3,5-diiodo-L-tyrosine, selenium, zinc and manganese in the form of their complexes with ethylenediaminetetraacetic acid (EDTA), and also additionally contains B vitamins₆ and PP (nicotinic acid) and water, with the following amounts of components per 1 liter of feed additive:

vitamin A 2,500,000 - 18,000,000 IU (0.84-6.05 g) vitamin B ₁ 0.5 - 5.0 g vitamin B ₂ 0.5 - 10 g vitamin B ₅ 4.0 - 17.0 g vitamin B ₆ 0.2 - 3.0 g vitamin D ₃ 490,000 - 5,000,000 IU (0.012-0.125 g) vitamin E 1.0 - 9.0 g vitamin PP 2.0 - 20.0 g zinc 0.5 - 1.5 g manganese 0.5 - 1.15 g

amino acids in the form

enzymatic hydrolyzate

vegetable protein 100.0 - 300.0 g selenium 0.025 - 0.09 g iodine 0.05 - 0.5 g water the rest up to 1 liter.

The proposed biologically active additive to human food or animal feed is a multicomponent preparation based on vitamins, amino acids and trace elements. It has a high biological activity, which determines its complex stimulating effect. Vitamins, which are part of the supplement, are catalysts for metabolic processes. The proposed supplement contains all essential and non-essential amino acids (as part of a high-cleavage enzymatic hydrolyzate), which are structural units of tissue proteins, enzymes, peptide hormones and other biologically active compounds. Thus, the proposed additive normalizes protein and general metabolism, which stimulates the human/animal immune system, live weight gain, productivity in animals, and egg production in poultry. Selenium, which is part of the supplement, is a microelement of the body's antioxidant defense, which helps to eliminate toxic substances. It is part of several selenoprotein enzymes, greatly contributing to the absorption of vitamin E and some trace elements (for example, iodine). Vitamin E, in turn, regulates redox processes and affects carbohydrate-fat metabolism, enhancing the action of vitamins A and D3. The use of a feed additive during unbalanced feeding, stress, during a period of intensive growth, reproductive processes and lactation strengthens the immune system and non-specific resistance of the body, improves appetite, improves the digestibility of feed, and has a beneficial effect on the condition of the coat and feather cover. The use of the proposed supplement for a person under stress, during a period of intensive growth, reproductive processes and lactation strengthens the immune system and nonspecific resistance of the body, improves the digestibility of food.

In the proposed additive, the concentration of peptone, that is, a mixture of amino acids and short peptides of the enzymatic protein hydrolyzate, is sharply increased.

For the preparation of the proposed biologically active additive, enzymatic peptone was used - amino acids in the form of an enzymatic hydrolyzate of vegetable protein, synthesized in-house, with a high degree of cleavage of 35-45%. The degree of cleavage of the used peptone α (and, consequently, its specific biological activity) is increased to 0.35-0.45 - against 0.10 and 0.20 for similar drugs - respectively, contains a large proportion of the most biologically active di- and tripeptides . They are the building blocks of cells.

The problem of alimentary deficiency of iodine and selenium is currently considered extremely acute and relevant - and not only for the Russian Federation and the CIS countries, but also for developed European countries.

The drug allows you to eliminate the lack of iodine and selenium in the diets of people and animals. Selenium is a synergist of vitamin E and iodine: with selenium deficiency, iodine is poorly absorbed by the body, and its biotransformation into triiodothyronine is greatly slowed down (which is due, in particular, to a lack of concentration of 5'-iodothyronine deiodinase, a key selenium-containing enzyme in thyroid tissues that converts thyroxine into significantly more active triiodothyronine (The interactions between selenium and iodine deficiencies in man and animals. Arthur JR, Beckett GJ, Mitchell JH. — Nutrition Research Reviews. 1999 Jun; 12(1):55-73).

A distinctive feature of the proposed additive is the complete absence of ionic forms of iodine (iodide, iodate, periodate ions). Iodine is present in dietary supplement/feed additive in conjunction with a highly physiological amino acid - L-tyrosine. As a result of chemical synthesis, this compound is obtained: 3,5-diiodine-L-tyrosine, which is an intermediate product of the process of biochemical synthesis of thyroid hormones from iodide ions. The molecule of this compound includes a strong covalent bond between the iodine atom and the carbon of the aromatic cycle.

Consider the benefits of using this form of iodine.

1. Solubility, chemical and pharmacodynamic stability. The iodine-containing component (3,5-diiodine-L-tyrosine) is highly soluble (up to 15-20 wt.%) and extremely stable during storage (at least 3-4 years, according to the "accelerated aging" method (I-42 -2-82 temporary instructions for carrying out work to determine the shelf life of medicines based on the method of "accelerated aging" at elevated temperatures, put into effect by order of the Ministry of Health of the USSR and the Ministry of Medical Industry on April 18, 1983 No. 430/224.) in slightly alkaline aqueous solutions, at pH 8.0-9.5.The components of the drug do not show any tangible interactions with each other - as well as with the protein, lipid and carbohydrate components of food products - during boiling in water.

The drug is completely indifferent in relation to the components of feed and premixes and can be used as a source of trace elements in feed production and in veterinary pharmacology.

2. Toxicity parameters. The extremely low toxicity of the proposed composition makes it impossible to correctly determine the LD50 values: at no physically achievable doses of the finished drug - or each of its two individual components - the death of experimental animals was recorded (tests were carried out on white rats of both sexes weighing 200 ± 25 g with oral the introduction of the maximum possible doses of concentrated drugs through a gastric tube). It was only possible to state that the LD50 value for pure iodine (as part of the 3,5-diiodine-L-tyrosine component) exceeds 1000 mg/kg. Thus, the toxicity of the drug for iodine is at least 10-15 times less than that of inorganic iodine compounds.

One of the most difficult stages on the way to the effectiveness of a drug is to overcome the cytoplasmic membrane of the cell. In order to get to the site of effect, most drug molecules must overcome this barrier.

The cytoplasmic membrane plays the role of a protective shaft, and nutrients enter the cell from the environment mainly through active transport through specialized pathways. Most drugs, however, cannot enter the cell through these mechanisms.

Short peptide (amino acid) sequences, which the proposed biologically active food or feed additive contains, have high biological activity and the ability to penetrate the cell membrane. Such peptides have an amazing property: they can penetrate into all types of cells and at the same time transport molecules associated with them into the cell, that is, carry active substances such as drugs into the cell (“With the right of access (Transport of drugs in living cells)”. Prof. M. Cristina Cardoso, Dr. Henry David Erse, Dr. Gisela Lättig-Thünnemann, TU Darmstadt, Labor&more, published 02/2012).

The table shows the formulations of the proposed biologically active additives.

Table

Component U/l Recipes one 2 3 Vitamin A IU 2 500 000 10,000,000 18 000 000 Vitamin B ₁ G 0.5 3.0 5.0 Vitamin B ₂ G 0.5 5.0 10.0 Vitamin B ₅ G 4.0 10.0 17.0 Vitamin B ₆ G 0.2 1.6 3.0 Vitamin D ₃ IU 490 000 3,000,000 5,000,000 Vitamin E G 1.0 5.0 9.0 Vitamin PP G 2.0 11.0 20.0 Zinc G 0.5 0.1 1.5 Manganese G 0.5 0.1 1.5 Amino acids in the form of an enzymatic hydrolyzate of vegetable protein with a degree of cleavage equal to 35-45% G 100 250 300 Iodine G 0.05 0.25 0.5 Selenium G 0.025 0.06 0.09 Water the rest up to 1 liter

All three formulations have the following effect on animals:

• effectively prevents anemia, endemic goiter, compensates for iodine deficiency and white muscle disease;

• normalizes metabolic processes, accelerates the growth of the animal's body, increases resistance and activates protective mechanisms, stimulates hematopoiesis;

• restores disturbed metabolism, eliminates the developmental delay (with malnutrition), weakened animals that have undergone various diseases;

• increases the nutritional value of the diet, increasing the digestibility of the feed and thus reducing the conversion rate;

• used in young animals to stimulate rapid growth, to increase productivity, in the presence of risk factors;

• increases the safety of animals with toxicosis of various etiologies;

• improves liver function (hepatoprotective effect);

• reduces the risk of infectious diseases;

• reduces terms of treatment and accelerates recovery;

• stimulates reproductive ability;

• in stressful situations has an adaptogenic effect;

• in fur animals, it enhances the therapeutic effect of antibiotics, vitamins and steroids in case of violations of the skin and coat of animals, improves the quality of fur and skins;

• has a beneficial effect on regenerative processes, accelerates the healing of wounds and fractures in animals;

• strengthens the musculoskeletal system.

All three formulations have the following effect on humans:

• effectively prevents anemia, compensates for iodine deficiency;

• normalizes metabolic processes, increases resistance and activates protective mechanisms, stimulates hematopoiesis;

• restores disturbed metabolism;

• increases the nutritional value of food;

• improves liver function (hepatoprotective effect);

• reduces the risk of infectious diseases;

• reduces terms of treatment and accelerates recovery;

• in stressful situations has an adaptogenic effect;

• beneficial effect on regenerative processes, accelerates the healing of wounds and fractures;

• strengthens the musculoskeletal system.

The proposed biologically active additive is obtained as follows.

Soy flour, pancreatin and methionine are mixed and a hydrolysis process is carried out, as a result of which amino acids are obtained in the form of an enzymatic vegetable protein hydrolyzate with a degree of cleavage equal to 35-45%. The resulting solution is decanted or separated, concentrated by evaporation, cooled, settled and decanted.

The resulting solution is heated to 80°C and zinc and manganese are introduced into it in the form of their complexes with EDTA. Cool the solution to 50°C, while the pH of the solution is 5-7.

A mixture of the resulting nanocolloid with 3,5-diiodine-L-tyrosine and vitamins B are introduced into the solution_one, B₂, B₅, B₆, B₉, C, and PP. A solution of vitamins A, E and D is poured into water with vigorous stirring.₃in detergent (Kolliphor or Solutol) and pour the mixture into the resulting solution. Conduct pasteurization and stabilization of the resulting product.

The iodine-containing component (3,5-diiodine-L-tyrosine) is obtained by combining iodine and tyrosine as follows:

The concentrated solution of L-tyrosine is iodinated by adding a solution of a mixture of iodate and potassium iodide, after which the reaction mixture is neutralized and cooled. The crystallizing product, neutral 3,5-diiodo-L-tyrosine, is separated by filtration, washed and dried.

Claims (2)

Dietary supplement containing vitamins A, B ₁ , B ₂ , B ₅ , D ₃ and E, zinc, manganese in the form of their complexes with ethylenediaminetetraacetic acid (EDTA), selenium, characterized in that it contains amino acids in the form of an enzymatic hydrolyzate of vegetable protein with a degree of splitting equal to 35-45%, iodine in the form of 3,5-diiodine-L-tyrosine, and additionally contains vitamins B ₆ and PP and water with the following amounts of components per 1 liter of supplement: vitamin A 2500000-18000000 IU vitamin B ₁ 0.5-5.0 g vitamin B ₂ 0.5-10 g vitamin B ₅ 4.0-17.0 g vitamin B ₆ 0.2-3.0 g vitamin D ₃ 490000-5000000 IU vitamin E 1.0-9.0 g vitamin PP 2.0-20.0 g zinc 0.5-1.5 g manganese 0.5-1.5 g amino acids in the form enzymatic hydrolyzate vegetable protein 100.0-300.0 g selenium 0.025-0.09 g iodine 0.05-0.5 g water up to 1 l