RU2323733C2 - Method of prevention of lesions caused by iodin radionuclides and optimisation of iodin metabolism in post-preventive period - Google Patents

Abstract

FIELD: medicine, veterinary.

SUBSTANCE: method implies administration of iodine-containing medicine, which contains organic iodine compound, into human or animal organism. And iodine is bound covalently with substance from the following groups: carbon acids, unsaturated lipid acids, lipids, terpens, terpenoids, isoprenes, peptides, polypeptides, amino acids, protein hydrolisates, polypeptide hydrolisates, proteins of plant and/or animal origin and/or microbiologic origin, mixture of lipids and unsaturated lipid acids, , mixture of isoprenes and terpens, mixture of isoprenes and protein hydrolisates, mixture of isoprenes and unsaturated lipid acids. At the same time, the proteins, peptides, polypeptides, amino acids, polypeptide and protein hydrolisates are taken so as iodine is bound covalently in 5 and 3 or 3 position of phenolic cycle, and amino acids and proteins don't show the hormonal thyroid activity. Single dose of medicine contains the sufficient iodine amount to provide its daily dose, which exceeds the physiologic requirement 10-1000 times.

EFFECT: method provides permanent prevention of lesions caused by radioactive iodine, by use of high dose of stable iodine isotope contained in medicine composition.

12 cl, 26 ex

Description

The technical field and the background of the invention

The invention relates to preventive, medical medicine and veterinary medicine and relates to the prevention and treatment of the population and animals from radioactive damage when exposed to radioactive isotopes of iodine.

Iodine is a structure-forming element of thyroid hormones, participates in the implementation of their biological function, is actively absorbed by the body. Iodine is part of various chemical compounds that undergo complex metabolism in the body.

Natural sources of iodine are represented by the stable element ¹²⁷ I, but man-made human activity has generated so far 24 more radioactive isotopes of iodine with different half-lives, energy and nature of decay. Chemically, these artificial radionuclides are practically complete analogues of the natural isotope ¹²⁷ I. During the operation of a nuclear reactor and the storage of spent heat-generating elements, ¹²⁹ I, ¹³¹ I, as well as other short-lived isotopes are generated and released. In the explosion of atomic bombs in the fission products of uranium, the radioactive isotopes of iodine make up 2.8 percent or more. Tellurium-132 has an effect on the body similar to iodine.

During a radiation accident of nuclear power plants in the initial period, also called the period of iodine hazard, a huge amount of ¹³¹ I is released into the environment. The period lasts only a few months due to the short half-life of the radionuclide. So, 2 months after the completion of radionuclide emissions at the Chernobyl nuclear power plant, the amount of ¹³¹ I decreased by 250 times.

Despite the relatively rapid decay of the radioactive isotopes of iodine due to the high rate of metabolism of iodine and its compounds, this time is enough to cause irreparable damage to human and animal health. The consequences associated with the incorporation of radioactive iodine into the body include the risk of cancer and a high degree of hypothyroidism. Iodine, its stable and radioactive isotopes, enter the body through the gastrointestinal tract, lungs, skin, is absorbed by the body not only in the form of elemental iodine or its inorganic compounds, but also enters the body as a part of various organic substances. The body’s usual source of iodine is its organic covalently bound form — iodinated amino acids tyrosine, histidine in a free state or as part of proteins. Proteins iodinated by these amino acids are well-known components of plant and meat food products, eggs, milk, and seafood.

If organic compounds of iodine are used as a source of iodine in a covalently bound form or when they enter the body, iodine not only accumulates in the thyroid gland or gastric mucosa, as occurs in the case of consumption of its inorganic compounds, but also enters practically any tissue of the body. Iodine from organic sources also has a higher dynamics of entry into the body and the intensity of tissue metabolism.

In order to prevent a significant accumulation of iodine radionuclides in humans or animals, it is customary to prescribe large doses of inorganic iodine compounds - 100-200 mg of iodine per dose (Big Soviet Encyclopedia, M .: Publishing House "Soviet Encyclopedia", v.10, p. 1090, 1972; A.D. Belov, V.A. Kirshin, N.P. Lysenko, L.V. Rogozhina. Radiobiology, M., Kolos, 1999). In their absence, it is recommended to use alcohol solutions of elemental iodine, enriching them with milk (3-5 drops of a 5% alcohol solution of iodine per glass of milk).

The intake of 100 mg of the stable isotope of iodine, which exceeds the daily requirement of an adult by 500 times, provides a protective effect on the human body for 24 hours. 100 mg of iodine consumed on the eve of infection with radioactive iodine blocks the absorption of iodine by the thyroid gland by 95% (Verger P. et. Al. Iodine kinetics and effectiveness of stable iodine prophylaxis after intake of radioactive iodine: a review, 2001, Thyroid, V.11 (4), P.353-360). The continued effect of iodine radionuclides on the body in the absence of further regular intake of stable iodine dramatically reduces the effectiveness of the thyroid blockade of the absorption of radioactive iodine. Regular intake of 15 mg of iodine per day is able to maintain the protection of the thyroid gland at the level of 90%. A stable iodine isotope preparation should be taken during the entire period of the body’s exposure to the threat of radioactive contamination with unstable iodine isotopes.

The necessary prophylactic dose of iodide as a source of iodine is 10 g per head for a lactating cow, and 1 g for a goat.

The traditional method of protecting the human and animal body from the damaging effects of the radioactive isotopes of iodine consists in diluting the excess of the stable isotope of iodine with radionuclides, thereby reducing the negative effect of the latter on the body, as well as blocking the accumulation of iodine by the thyroid gland, the main organ that deposits iodine. The thyroid gland accumulates and uses the bulk of the iodine entering the body. Thyroid hormones, the iodine-containing product of the thyroid gland, are received from the blood by almost all body tissues. Thyroid hormones are known to control gene expression, therefore, the inclusion of iodine radionuclide in the hormone molecule carries the risk of damage to the genetic apparatus of the cell.

Obviously, the same drugs are used for radionuclide prophylaxis as in the case of replenishment of iodine deficiency. Alkali metal iodides used for the prevention of iodine-deficiency conditions and radiation safety are chemical unstable, unsuitable for long-term storage, and require reliable packaging. In the case of radioprophylaxis, it is recommended to take into account a number of factors related to age, the functional state of the thyroid gland, and the level of iodine consumed with food by a specific individual. However, the main drawback is the low physiological effectiveness of iodide ions, which are not accessible to interstitial exchange and excessive consumption of which causes serious health consequences. The risk of inducing hyperthyrosis in younger age groups of people is justified by the more serious risk of thyroid cancer mediated by radiation exposure. In older age groups, the benefits of therapy or the prevention of thyroid damage from iodides are inferior to the risk of iodine-induced hyperthyrosis.

The situation does not undergo major changes in the case of using more stable compounds, such as iodates. These compounds in the body behave similarly to iodides. In large quantities, comparable with the radioactive nucleotides of iodine necessary for the prevention of damage to the body, iodates are highly toxic and enter the body tissues as iodate, rather than iodide, anions.

For the same biochemical reasons, the use of such organic compounds as amyloiodine and iodinol as an iodine source is ineffective. The disadvantage of these drugs is the same non-covalent nature of the relationship of iodine with an organic carrier. Therefore, these substances behave in the body as sources of mineral iodine.

A well-known drug for the prevention and treatment of thyroid diseases, which is an organic compound with covalently bound iodine, is iodinated thyroidin protein (Big Medical Encyclopedia, Moscow: Sovetskaya Encyclopedia Publishing House, v. 25, p. 79, 1985). However, thyroidin has hormonal activity and therefore is not applicable for the purposes of radiation prevention, especially since large doses of the drug must be administered over a sufficiently long period. Taking the hormonal drug thyroidin as a source of iodine is unacceptable, since it leads to the replacement of one's own hormones with those coming from the outside, and in the case of radioprophylactic measures, the amount of hormone administered will significantly exceed its physiological level.

Known drug (Physiology of farm animals, under the editorship of N.A. Shmanenkov, L., "Science", 1978, S.505-506) containing iodine in an organically bound form - iodinated protein iodine casein. But the disadvantage of this drug is that it is a hormonal drug and was used in animal husbandry to regulate productivity.

For the prevention of iodine deficiency in the animal’s body, inorganic iodine - potassium iodate or potassium iodide is also used by their inclusion in feed mixtures and feed additives: patent RU 2041647, cl. A23K 1/16, 08.20.1995, as well as patent RU 2164758, class. A23K 1/16, 04/10/2001. The disadvantage of such feeds and additives is the difficulty in ensuring normalized iodine consumption due to technical difficulties in the preparation of such iodine-containing feeds and additives. In addition, the mineral compounds of iodine are not a physiologically adequate form of iodine for the animal’s body and, unlike organic iodine-containing substances, in vivo act only as an auxiliary source of iodine.

A number of feed additives and feeds based on various seaweeds are known: kelp, spirulina, chlorella (patent RU 2134522, class A23L 1/30, 08/20/1999, patent RU 2131198, class A23K 1/00, 06/10/1999) . However, the preparation of such additives and feed requires a special technology and can be quite an expensive process. The use of these drugs is based on the traditional way of enriching the diet with inorganic iodine compounds.

In 1998-2000, a new method was proposed for eliminating iodine deficiency in the human body: RF patent No. 2134520, class. A23J 1/00, 1998, RF patent No. 2141205, class. 6 A21D 2/02, RF patent No. 2163127, class. 7 A61K 33/18. The method is based on the fact that the main evolutionarily selected and genetically fixed mechanism that provides the body with iodine is the process of using covalently bound iodine from exogenous non-hormonal iodine-organic compounds. The possibility of various metabolic modifications of organic compounds with covalently bound iodine ensures the effective regulation of iodine metabolism and the supply of the thyroid gland with the necessary iodide ions. Contrary to the established wide practice of replenishing iodine deficiency with inorganic iodine compounds, in vivo such an iodine supply to the body is only auxiliary.

Due to the high metabolic activity of iodine inherent in its radionuclides, a significant amount of radioactive iodine enters the body with milk, products of plant origin. For example, a cow grazing in a pasture infected with radioactive isotopes of iodine removes 0.81% of the iodine consumed with 1 liter of milk (D. Hoffman. Chernobyl accident: radiation consequences for present and future generations, Minsk, Vysheyshaya Shkola, 1994), it was found that Of the total 48.8 rem, accumulated by the thyroid gland in the infected area, 42.9 rem is due to the consumed milk. The total composition also includes the dose received with organic iodine from plant foods.

Iodine in animal products, including milk, crop products, is represented mainly by organic compounds. This fact has not been given due attention for a long time. The metabolism of organic iodine compounds is significantly different from the metabolism of iodide ions, a different dynamics of iodine accumulation is manifested. Stable inorganic iodine has a limited effect on total iodine metabolism. It practically does not replace organic non-hormonal iodine in tissues, at least during the first 4-8 hours after administration to the body.

Thus, the disadvantage of the traditional method of protecting the body from the damaging effects of the radioactive isotope of iodine is its lack of effectiveness, which is due to the use of its inorganic compounds as a source of stable iodine, and a high risk of inducing hyperthyroid and other pathological conditions of iodine metabolism. The problem of preventing the negative effects of iodine radionuclides is that this event induces essentially pathophysiological iodine metabolism in the body, due to the intake of huge amounts of the stable iodine isotope both in a single form and for a fairly long time. Such iodine metabolism and the physiological and biochemical state of the human and animal organism caused by it are fundamentally different from the physiological state of the body when taking a moderate excess of iodine, even in the case of previous iodine deficiency. The use of compounds with covalently bound organic iodine as a source of iodine for humans and animals suggests a new effective solution to the problem of protecting the body from radiation damage by iodine radionuclides and optimizes the post-prophylactic state of the body due to the significant excess intake of the stable iodine isotope in the body during prevention.

SUMMARY OF THE INVENTION

The present invention is directed to solving the problem of effective protection of the population and animals from the damaging effects of the radioactive isotopes of iodine.

The task is to use new chemical iodine compounds that have properties that allow you to implement the biochemical features of the metabolism of organic iodine in the body as an alternative to inorganic iodine compounds with radiation protection from the damaging effects of iodine radionuclides.

The present invention is aimed not only at solving the problem of preventing the damaging effects of iodine radionuclides, but also at weakening potential iodine metabolism disorders in humans and animals as a result of preventive measures. Prevention of potential damage by iodine radionuclides primarily includes a mechanism for diluting the concentration of the radionuclide. Further, large amounts of the stable isotope of iodine in the form of an iodide ion block the accumulation of iodine, including radioactive, thyroid gland. However, the use of large doses of inorganic iodine has serious consequences for the body in the post-prophylactic period. The task is to create and use an iodine radioprotector, which is iodine-containing compounds of organic origin that do not have hormonal activity, are biochemically adequate to iodine metabolism, capable of triggering self-monitoring and auto-regulation of iodine metabolism when iodine is used in concentrations significantly exceeding the physiological level, i.e. with pathological iodine metabolism.

This problem is solved in that for the prevention of iodine radiation damage, iodine-containing organic matter is used, in which iodine is in a covalently bound form.

According to the invention, the preparation includes an organic compound of iodine covalently bound to a substance selected from the group of carboxylic acids, unsaturated fatty acids, lipids, terpenes, terpenoids, isoprenes, peptides, polypeptides, amino acids, protein hydrolysates, polypeptide hydrolysates, vegetable proteins, and / or animal and / or microbiological origin, a mixture of lipids and unsaturated fatty acids, a mixture of isoprenes and terpenes, a mixture of isoprenes and protein hydrolysates, a mixture of isoprenes and unsaturated fatty acids wherein, proteins, peptides, polypeptides, amino acids, polypeptide and protein hydrolysates are selected where iodine is covalently linked at the 5th and 3rd or 3rd position of the phenolic cycle, and amino acids and proteins do not have hormonal thyroid activity, while a single dose of the drug contains such the amount of iodine to provide a daily dose of iodine exceeding the physiological need for it by 100-1000 times.

It is advisable to use casein, egg albumin, milk or whey proteins, hemoglobins as animal proteins, soy protein as vegetable proteins, and yeast proteins as a product of yeast hydrolysis, for example, as microbiological proteins.

Organic matter is obtained with covalently bound iodine by a chemical or biotechnological method or isolated from natural sources, for example, marine plants or animals.

Additionally, the preparation may contain an organic compound with non-covalently bound iodine and / or inorganic iodine.

The drug may be a prolonged form. It is advisable to carry out in the form of tablets, powders, capsules, microcapsules, dragees, solutions. In this case, microcapsules are obtained by microencapsulation using carbohydrate, protein or lipid raw materials.

An iodine-containing substance can be included in an inert polymer matrix, for example, from carrageenan, pectin, agarose or uronic acids.

The drug can be part of vitamin-mineral complexes designed to prevent possible damage by other radionuclides.

An iodine-containing preparation is used under the conditions accepted for its inorganic analogues, i.e. depending on the exposure time with radioactive iodine, the dose of the radionuclide, the age and physiological state of the body.

Detailed Description of the Invention

The following compounds are provided for use in the present invention: proteins, peptides and polypeptides. Here, these concepts are divided and apply to different groups of substances, based on the following definitions.

Peptides are organic compounds consisting of two or more amino acid residues linked by peptide bonds, and which can also be obtained as products of the incomplete hydrolysis of polypeptides or proteins. Peptides containing more than ten amino acid residues are called polypeptides (A.Leninger. Fundamentals of biochemistry. M., Mir, 1985, p.132).

Proteins — high-molecular nitrogen-containing organic compounds, are polypeptide chains containing from 100 to 1000 or more amino acid units connected to each other by peptide bonds (ibid., P. 160).

The proposed organic iodine-containing compounds that are part of the drug for the prevention of radiation infection with iodine radionuclides do not have hormonal activity, they contain iodine in a covalently bound form. This form of iodine allows you to use these substances as a source of iodine, and as a substrate, which allows optimizing iodine metabolism as a whole.

As mentioned above, the embodiment of the invention can be performed in several combinations. A preparation for the prevention of radiation infection with iodine radionuclides includes an organic compound of iodine covalently bound to a substance selected from the group of carboxylic acids, unsaturated fatty acids, lipids, terpenes, terpenoids, isoprenes, peptides, polypeptides, amino acids, protein hydrolysates, polypeptide hydrolysates, vegetable proteins, and / or animal and / or microbiological origin, a mixture of lipids and unsaturated fatty acids, a mixture of isoprenes and terpenes, a mixture of isoprenes and protein hydrolysates, sm and isoprene, and unsaturated fatty acids, the proteins, peptides, polypeptides, amino acid, polypeptide and protein hydrolysates are chosen where iodine is covalently bound at the 5- and 3 or in the 3-position of the phenolic cycle, amino acids and proteins do not possess the thyroid hormone activity.

Therefore, if you list in detail all the combinations of the embodiments of the invention, the preparation for the prevention of radiation infection with iodine radionuclides may contain one of the following compounds:

peptides in which iodine is covalently bonded at the 5th and 3rd position of the phenolic ring, peptides in which iodine is covalently bonded at the 3rd position of the phenolic ring,

polypeptides in which iodine is covalently linked at the 5th and 3rd position of the phenolic ring, polypeptides in which iodine is covalently linked at the 3rd position of the phenolic ring,

polypeptide hydrolysates in which iodine is covalently bonded at the 5th and 3rd position of the phenolic cycle, polypeptide hydrolysates in which iodine is covalently bonded at the 3rd position of the phenolic cycle,

amino acids in which iodine is covalently bonded at the 5th and 3rd position of the phenolic cycle, amino acids in which iodine is covalently bonded at the 3rd position of the phenolic cycle, and these amino acids are selected from the group of amino acids that do not have hormonal thyroid activity,

protein hydrolysates in which iodine is covalently bonded at the 5th and 3rd position of the phenolic cycle, protein hydrolysates in which iodine is covalently bonded at the 3rd position of the phenolic cycle,

proteins of plant origin in which iodine is covalently bound at the 5th and 3rd position of the phenolic cycle, proteins of plant origin in which iodine is covalently bound at the 3rd position of the phenolic cycle, and these proteins are selected from the group of proteins that do not have hormonal thyroid activity and which are obtained under conditions excluding the condensation of tyrosine nuclei,

proteins of animal origin in which iodine is covalently bonded at the 5th and 3rd position of the phenolic cycle, proteins of animal origin in which iodine is covalently bonded at the 3rd position of the phenolic cycle, and these proteins are selected from the group of proteins that do not have hormonal thyroid activity and which are obtained under conditions excluding the condensation of tyrosine nuclei,

proteins of microbiological origin in which iodine is covalently linked at the 5th and 3rd position of the phenolic cycle, proteins of microbiological origin in which iodine is covalently linked at the 3rd and 3rd position of the phenolic cycle, and these proteins are selected from the group of proteins that do not have hormonal thyroid activity,

a mixture of isoprenes and protein hydrolysates in which iodine is covalently bonded at the 5th and 3rd position of the phenolic ring, a mixture of isoprenes and protein hydrolysates in which iodine is covalently bonded at the 3rd position of the phenolic ring,

a mixture of proteins of plant, animal and microbiological origin, in which iodine is covalently linked in the 5th and 3rd position of the phenolic cycle, a mixture of proteins of plant, animal and microbiological origin, in which iodine is covalently bound in the 3rd position of the phenolic cycle, these proteins being selected from the group of proteins, not having hormonal thyroid activity,

a mixture of proteins of plant and animal origin in which iodine is covalently linked at the 5th and 3rd position of the phenolic cycle; a mixture of proteins of plant and animal origin in which iodine is covalently bound at the 3rd position of the phenolic cycle, and these proteins are selected from the group of proteins that do not have hormonal thyroid activity

a mixture of animal and microbiological proteins in which iodine is covalently linked at the 5th and 3rd position of the phenolic cycle, a mixture of animal and microbiological proteins in which iodine is covalently linked at the 3rd and 3rd position of the phenolic cycle, and these proteins are selected from the group of proteins that do not have hormonal thyroid activity

a mixture of proteins of plant and microbiological origin, in which iodine is covalently bound in the 5th and 3rd position of the phenolic cycle, a mixture of proteins of plant and microbiological origin, in which iodine is covalently bound in the 3rd position of the phenolic cycle, these proteins are selected from the group of proteins that do not have hormonal thyroid activity.

For the production of a drug for the prevention of radionuclide infection, simple, combined and prolonged forms of iodine-containing compounds are offered that provide an individual approach to the prevention of radionuclide infection.

The intestinal epithelium carries out differentiated absorption of iodine - absorption of iodide and transmembrane transfer of organic compounds with covalently bound iodine. In the latter case, iodine is absorbed as a single complex with an organic carrier without prior release in the intestine. Subsequently, iodide from the intestine enters the bloodstream and is stored by the thyroid gland, and covalently bound organic iodine becomes accessible to tissue metabolism and acquires the ability to be deposited in the tissues of the liver, spleen, muscle tissue, cardiac muscle, blood, etc. An essential role in the metabolism of iodine-organic compounds the liver plays, where the enzymatic cleavage of chemically bound iodine is carried out in the form of an iodide ion, which is removed by the thyroid gland from the blood for its synthetic needs. Along with deposition in the liver, iodine-containing metabolites are modified by conjugation with glucuronic acid for their subsequent excretion in urine or bile. Iodinated amino acids undergo transamination, decarboxylation, oxidation, oxidative deamination. Iodine-containing pyruvate and acetate analogues can be excreted in the urine. Thus, iodine-containing compounds realize almost all the metabolic capabilities of iodine metabolism, and this, in turn, provides the body with great potential in maintaining auto-control and self-regulation of this process. As experiments have shown, this is true not only for the exchange of physiological amounts of iodine-containing compounds, but also for essentially pathological iodine metabolism with the introduction of superphysiological quantities of these compounds into the body, which is required for the effective prevention of radioactive damage.

The experiments on rats using the radioactive indicator ¹³¹ I as part of the inorganic iodine compound and ¹²⁵ I as the component of the organic compound when the animals were fed a moderately increased amount of iodine (50 μg per day) for 1 month confirmed a significant accumulation of chemical compounds with covalently bound iodine (mono - and diiodotyrosines) in the tissues of the kidney, heart, liver, spleen, in muscle tissue within 8 hours after oral administration of iodized protein. Control studies with inorganic iodine confirmed the well-known fact of the absence of such capabilities in the iodide ion. In the thyroid gland, a significant accumulation of radioactivity was observed only from 4 hours after drug administration. Despite the inability of the thyroid gland to accumulate iodotyrosines or their capture in extremely insignificant volumes, the amount of iodine captured by the thyroid gland from an organic source is almost an order of magnitude higher than the amount of iodine received from an inorganic source during the first 4 hours, despite the fact that iodine was introduced into both compounds in equal amounts. Therefore, the metabolism of covalently bound iodine in organic compounds is characterized by a higher rate. A higher level of iodine metabolism is inherent in the liver. Despite the relatively low specific accumulation of iodotyrosine by muscles, they significantly affect the overall picture of iodine metabolism, given their total mass in the body. The high metabolic rate of iodine organics is seen from the pattern of excretion of iodine with urine and feces. During the day, 32.6% of injected iodine with urine and 15.25% with feces are excreted from iodotyrosines from 4.8% and 2.2%, respectively, from a source of inorganic iodine. In experiments performed on animals that received various amounts of iodothyrosine-containing protein, it was found that with a low iodine supply (2-5 μg iodine per day per rat), the animal’s thyroid gland accumulates 31.8% of orally administered iodine per day, while at a high level of iodine intake (50 μg of iodine per day per rat), iron stores 6.38% of the iodine intake, and at a high level of consumption (1000 μg iodine per day per rat), the thyroid gland captures only 0.025% of the administered dose. The experiment revealed the unambiguous advantages of the covalently bound form of iodine in the prevention of damage to the radioactive iodine nuclides in comparison with the generally accepted ones. A month-long experiment in rats with a 200-fold excess of iodine in the diet represented by iodotyrosine did not reveal morphological pathologies in rats despite prolonged consumption of high doses of iodine.

The absorption of iodine in the intestine is one of the key factors in maintaining its homeostasis in the body and is the result of both the physiological state of the intestine and the functional state of the biochemical mechanisms of absorption. The proposed invention allows you to directionally affect these processes using various classes of iodine-containing drugs. For example, when iodized amino acid and iodinated fatty acid are absorbed, various mechanisms of transmembrane transfer and their further tissue metabolism are involved. Since tissue dehalogenases with various efficiencies perform deiodination of a variety of organic iodine substrates, this makes it possible to regulate iodine metabolism at the stage of iodine cleavage from the organic component and its entry into the bloodstream, as well as at the level of peripheral metabolism. It is proposed to use various forms of iodine-containing preparations, which not only provide the body with iodine, but also optimize iodine metabolism due to the peculiarities of their metabolism.

As experiments showed, only iodine-containing compounds with covalently bound iodine provide an increase in the effectiveness of the prevention of iodine damage by radionuclides, since:

- specific transmembrane transport systems for the transfer of iodine-containing substances in the intestine are involved;

- tissue deposition of non-hormonal organic compounds with covalently bound iodine is provided. The main regulator of iodine metabolism is muscle tissue, in which half of the non-hormonal organic iodine entering the body accumulates;

- the prolonged nature of the intake of iodide from tissues into the bloodstream is ensured;

- it is possible to control the rate of release of iodide by tissue dehalogenases due to the variability of the substrate specificity of iodine-containing compounds, which is determined by the nature of the organic carrier of iodine;

- Organic chemically bound iodine inhibits the intake of iodide into the body from mineral sources of iodine;

- tissues accumulate organic iodine compounds through a specific carrier;

- the ability of tissues to accumulate organic chemically bound forms of iodine depends on the iodine supply of the body;

- thyroid tissue, in contrast to other body tissues, accumulates iodine mainly in the form of an iodide ion;

- tissues differ in speed and amount of accumulation of organic iodine compounds per unit mass;

- the body has an effective system for maintaining the normal balance of iodine when using an organic covalent form as its source, including when the daily requirement of a microelement is significantly exceeded;

- covalently bound organic iodine is an effective source of iodine for the body.

Thus, unlike stable inorganic iodine compounds, covalent non-hormonal organic iodine compounds have a number of additional advantages over the former, due to the specificity of their metabolism, and these advantages, which is especially important, are also preserved during essentially pathological iodine metabolism, when nonphysiological extremely large the amount of bound iodine. This has a positive effect on the post-prophylactic state of the body and the post-prophylactic optimization of iodine metabolism. Unlike iodides, organic compounds of covalently bound iodine are more stable during storage and technological impact.

It is advisable to use the drug in the form of simple, combined and prolonged forms. The simple form is an organic compound of a non-hormonal nature, containing covalently bound iodine. Iodine-containing synthetic substances are obtained by iodination of organic compounds of various classes, for example, a phenolic derivative, which is tyrosine, both in the free state and in the composition of a protein, derivatives of a terpene, terpenoid or isoprene nature, unsaturated fatty acids, lipids, proteins or peptides, polypeptides, protein or polypeptide hydrolysates, as well as the previously indicated mixtures of certain compounds. Iodization of organic substances is carried out chemically or enzymatically, either simultaneously chemically, and enzymatically, or biotechnologically, using known methods for this (see Osterman L.A. Research of biological macromolecules. M., Science, 1983, p. 244; Hager LP "Iodination of Tyrozine by Chloroperoxidase", In "Methods in Enzymology", v. XVII, Part A, Acad. Press, NY, London, 1970; Morrison M. "Iodination of Tyrozine: Isolation of Lactoperoxidase", In "Methods in Enzymology ", v. XVII, Part A, Acad. Press, NY, London, 1970; Missouri. Agric. Exp. Stat., Research Bull, v. 355, 1942; Hunter WM, Greenwood FC, Nature, London, v .194, 1962, p. 495).

In this case, amino acids and proteins are selected from the group of amino acids and proteins that do not have hormonal thyroid activity, and which are obtained under conditions that exclude the condensation of tyrosine nuclei.

It is advisable to carry out iodination of peptides, polypeptides, proteins on tyrosine amino acid residues.

It is advisable to obtain a synthetic organic substance with covalently bound iodine by hydrolysis of pre-iodinated proteins or polypeptides.

It is advisable to obtain iodinated proteins, peptides, amino acids, lipids from natural sources: tissues of marine plants and animals.

It is useful to use iodinated unsaturated fatty acids as a organic substance with covalently bound iodine in a free or chemically bound state or in a combination of free fatty acids and their chemical compounds.

It is useful to produce combined forms of iodine-containing preparations, which are a combination of organic iodine in covalent form and organic iodine in non-covalent form, as well as organic iodine in covalent form and inorganic iodine. Such drugs use alternative mechanisms of iodine absorption and are indicated for iodine metabolism disorders at this stage.

It is advisable to use a prolonged form of an iodine-containing substance - a synthetic organic compound with covalently bound iodine, included in an inert polymer matrix having a three-dimensional molecular sieve structure, or in a microcapsule (microsphere) of protein, lipid or carbohydrate nature. The polymer matrix or microcapsule (microsphere) renders steric hindrance to the release of iodine organics, prolonging this process and, consequently, the absorption process. Steric difficulties for the proteolysis of iodinated proteins or peptides incorporated into the polymer also prolong the release of iodine-containing amino acids and their absorption. A prolonged form of an iodine-containing preparation can be represented by a combination of iodine-containing compounds of various nature - a combination of inorganic, covalently and non-covalently bound iodine in organic compounds. To obtain a polymer matrix, agarose, pectins, alginic acid, carrageenan, uronic acids can be used. For the purpose of prolongation, microcapsules are obtained by microencapsulation using carbohydrate, protein or lipid raw materials. Moreover, the prolonged form of the iodine-containing substance may be the previously indicated mixtures of synthetic iodine-containing substances of various chemical nature.

It is advisable to use the drug in the form of a solution for injection, which will ensure that iodine enters the body of the animal for several months in the absence of regular feeding with iodine-containing additives.

It is possible to carry out prophylaxis against damage by iodinated organic compounds with iodinated radionuclides using them as part of biologically active food additives, in various forms of vitamin-mineral complexes and various food products. Food fortification is carried out using iodine-based organics in dry form or in the form of a solution. Local production of such food products is easy to establish and provide mass prevention.

The consumption of all forms of iodine-containing compounds for animals for the purpose of radiation safety is regulated in accordance with the relevant veterinary, species and prophylactic boundaries and norms established for iodine. The introduction of iodized organic compounds into the animal's body can be carried out as a part of biologically active feed additives, in various forms of vitamin-mineral premixes and various feed products. Feed enrichment is carried out using iodine-based organics in dry form or in the form of a solution.

Organic substances containing covalently bound iodine have chemical stability, thermal and light stability, good solubility in water or organic solvents. The physicochemical properties of these compounds make it possible to use them to enrich a wide range of animal feeds and a wide range of food products - dairy and lactic acid, meat, bread and bakery products, confectionery, drinks, juices, baby food, etc. This is important because in the absence of , for example, ready-made preparations of iodine-organic compounds for radioiodine prophylaxis in local conditions it is easy to establish the production of prophylactic food products with a significantly increased but normalized content of BEATER iodine for mass coverage in the prophylaxis period.

Since the proposed methods of iodination and organic substances of various chemical nature selected for this provide a high degree of iodination, the iodine-containing substances thus obtained are used in small quantities, and their substantial effect on the organoleptic properties of the enriched product is excluded.

The technical result of the invention is to increase the effectiveness of the prevention of radiation iodine safety, expanding the range of prophylactic agents used for the threat of radiation infection, reducing the level of pathologies of iodine metabolism as a result of the use of high doses of iodine, which is ensured by the metabolic characteristics of iodine-containing compounds in humans and animals.

Examples of carrying out the invention

The invention is illustrated by the following examples, which, however, do not cover, and even more so do not limit the entire scope of the claims of this invention.

Example 1

The drug for the prevention of damage by iodine radionuclides and the optimization of iodine metabolism in the post-prophylactic period is obtained by iodization of food protein casein rich in tyrosine amino acid residues.

Protein iodination is carried out primarily on tyrosine amino acid residues by replacing hydrogen atoms with iodine at the 5th and 3rd positions of the phenolic cycle and histidine at the 3rd position of the imidazole cycle. Iodination is carried out under conditions that exclude the condensation of tyrosine phenolic nuclei with the possibility of the formation of iodinated thyronins, which include triiodothyronine and tetraiodothyronine - compounds with thyroid hormonal activity. The degree of protein iodization is also regulated by the reaction conditions. The high iodine content (more than 8%) allows you to use the drug for food fortification in small quantities. To ensure the entry into the human body of 100 mg of iodine, it is necessary to introduce 1300 mg of iodized protein into 350 g of bread. Such an amount of the drug does not affect the organoleptic properties of the food product.

Cow's milk (120 L) is degreased by separation and concentrated by ultrafiltration on roll filters with a retention threshold of 10 kDa. When milk is acidified to pH 4.6, the casein fraction of the protein is isolated. The resulting casein (about 3 kg) is dissolved using a sodium hydroxide solution. The protein solution is placed in a thermostatic reactor equipped with a mixing device. For iodination, elemental iodine is used - finely crystalline and instant. During the reaction, temperature, pH, and the required degree of iodization are controlled. At the end of the reaction, iodinated caseins are purified from the inorganic form of iodine. Iodide is removed by protein reprecipitation using centrifugation and ultrafiltration. Diafiltration is carried out on roll filters with a retention threshold of 10 kDa until the final iodide content in the total amount of iodine in the preparation is less than 0.1%. The iodization process provides highly effective antiseptic processing of a solution of milk proteins.

The purified iodinated proteins are preserved. The solution is additionally sterilized by short-term (3-5 minutes) heating to 90 ° C. The solution of iodized protein is Packed in glass jars and sealed under vacuum. The guaranteed shelf life of the drug is 1-1.5 years.

The resulting solution of iodinated casein is used to enrich the bread. The protein solution is added to the batch before adding flour, thereby achieving a uniform distribution of iodized protein in the dough and the finished product.

Iodine is bound to tyrosine amino acid residues by a covalent bond. These compounds are characterized by thermal stability. The decomposition of iodotyrosine occurs at 199-201 ° C. Thus, the technological process of baking bread despite a rather high temperature does not affect the chemical stability of the organic compound with covalently bound iodine.

The amount of iodinated casein added to bread is determined by regulatory documents, it depends on the degree of radiation damage to the region, the rate of average per capita consumption of bread, the degree of iodization of the protein itself. Typically, the input rate is the amount of iodized protein, providing 100 mg of iodine per day per person.

The iodinated protein in the gastrointestinal tract is hydrolyzed to free amino acids. Iodotyrosines are absorbed by the intestinal mucosa as a single chemical compound without prior release of iodine. Absorbed iodotyrosines with blood flow are available to various body tissues. In cells, iodotyrosines undergo a variety of biochemical transformations. Enzymatic deiodination releases free iodide, which becomes available to synthetic processes in the thyroid gland. The dynamics of iodide intake in tissues and the thyroid gland when using its organic covalently bound form as an iodine source is fundamentally different from that in the initial consumption of iodine in the form of its inorganic compounds. The iodide released from the iodine organic is more effectively captured by the thyroid gland, blocking the intake of the radionuclide, and also limits the accumulation by the body's tissues of the radioactive isotopes of iodine in organic compounds from contaminated food products. Iodotyrosines inhibit the intake of iodide, including as a radionuclide ion, through the gastrointestinal tract and into the thyroid gland. Iodotyrosines can be deaminated, decarboxylated, oxidized along the tyrosine ring, conjugated with glucosiduronic or sulfate groups. The resulting conjugates can be extracted with bile. Iodized metabolites are also excreted in the urine.

Thus, iodine-containing amino acids with covalently bound iodine not only serve as an effective source of iodine for massive blocking of iodine radionuclide contamination, but also provide self-regulation of iodine metabolism in the body after iodine prophylaxis, since they are available for various biochemical transformations. Due to this, the body is able to more easily tolerate a sufficiently large excess of iodine in the form of its organic compounds. Iodinated caseins, both in the chemical nature of iodine-containing compounds and in the nature of their metabolism, are analogues of natural iodized compounds - the main source of iodine for the human body. A high degree of protein iodization allows the use of the drug in small quantities.

Example 2

The drug for the prevention of damage to iodine by radionuclides and the optimization of iodine metabolism in the post-prophylactic period as an iodine source contains tyrosine iodized soy protein together with iodinated starch iodine. Soy protein is dissolved in water and iodination is carried out by analogy with example 1, but 1.5-2 times less iodine is used. An acidified starch solution (5%) is iodinated with a five percent alcohol solution of elemental iodine. Iodine from such a combined preparation enters the body differentially: in the form covalently linked to an amino acid and in the form of inorganic iodine. Despite the high degree of association of iodine with starch, the latter releases a limited amount of iodine as a result of dissociation. Recovering to iodide, iodine enters the bloodstream. Thus, the combined form of the drug involves alternative mechanisms of absorption and metabolism of iodine. This form of the drug provides a faster intake of iodine in the thyroid gland, allows you to effectively block the mucous membrane of the stomach and intestines from the accumulation of radioactive iodide, and ensures the absorption of iodine by independent biochemical mechanisms, which is important in case of any pathology in the gastrointestinal tract.

Example 3

The drug is intended for the prevention of damage to iodine radionuclides and the optimization of iodine metabolism in the post-prophylactic period, obtained in the form of a combined preparation including potassium iodate as an inorganic compound of iodine and an organic covalently bound form of iodine - egg albumin iodinated by tyrosine and histidine, which is synthesized by analogy with an example 1, but with the exception of heat treatment, which is replaced by sterilizing microfiltration. Such a combined preparation provides the inclusion of alternative mechanisms for the absorption of iodine and additionally protects the mucosa of the gastrointestinal tract from radiation damage by iodine radionuclide. Iodate is absorbed into the blood like iodide, but is characterized by greater chemical stability.

Example 4

The drug is intended for the prevention of damage to iodine radionuclides and the optimization of iodine metabolism in the post-prophylactic period, made from hydrolysates of iodized dietary hemoglobin protein, obtained under the conditions corresponding to example 1, and included in a gelatin capsule. As a stabilizer, hyaluronic acid is used. The capsule has a prolonged effect. The drug is soft, does not affect the mucous membrane. Capsules are convenient to take, they are small in size, have no taste or smell.

Example 5

A fat-soluble preparation is prepared for the prevention of iodine damage by radionuclides and the optimization of iodine metabolism in the post-prophylactic period in the form of a mixture of extremely iodinated unsaturated fatty acids - linolenic, arachidonic, linoleic, using, for example, refined sunflower or linseed oil. This form of the preparation is suitable for preparing capsules containing, for example, 25, 50, 100 mg of covalently bound iodine. Capsules are intended for oral administration in case of danger of exposure to iodine radionuclides. This drug has a prolonged effect, since it is absorbed, for example, as a fatty acid into lymph, it is stored in a fat depot. Iodine from these compounds is released as a result of enzymatic catalysis. The advantages of such a preparation are that it is possible to administer large doses of covalently bound iodine, excluding the single release of free iodide in large quantities. This form of radioprotective drug allows a single dose of 200-400 mg of bound iodine. Reception of such amounts of bound iodine is safer for the body than comparative amounts of the inorganic form of iodine based on post-prophylactic effects.

Example 6

The drug for the prevention of iodine damage to radionuclides and the optimization of iodine metabolism in the post-prophylactic period based on a mixture of iodized protein hydrolyzate obtained from iodinated egg albumin and iodinated carotene, an isoprene derivative, is part of the vitamin-mineral complex. Such a preparation provides the body with organic iodine, enhances the biochemical effect of the vitamin-mineral complex. The normalized intake of such iodine is consistent with established standards.

Example 7

The drug for the prevention of damage by iodine radionuclides and the optimization of iodine metabolism in the post-prophylactic period of prolonged action is part of the vitamin-mineral complex. It is made in the form of tablets from a polymer matrix based on alginic acid. In a 4% solution of alginic acid make iodized whey milk protein, which is iodized in accordance with example 1, a mixture of vitamins and minerals. The alginate solution is polymerized by introducing a 1 M calcium chloride solution, molded and dried. One tablet contains 100 mg of covalently bound organic iodine.

In the gastrointestinal tract, the alginate polymer matrix creates steric barriers to the enzymatic hydrolysis of the iodized protein and the release of iodine-containing amino acids. The polymer matrix prolongs the absorption of iodine in the intestine and prolongs the time period for dilution of the radionuclide in the chyme. This form of the drug allows you to enter it into the body in large quantities.

Example 8

Iodinated amino acids monoiodotyrosine and diiodotyrosine are used as a drug for the prevention of damage to iodine radionuclides and the optimization of iodine metabolism in the post-prophylactic period. They are characterized by an extremely high iodine content - 41.4% and 58.7%, respectively. This degree of iodination, despite the limited solubility of these compounds in water, allows them to be effectively used to enrich drinks. The small size of the molecules of the iodine-containing substance ensures effective sterilization of iodized drinks by ultrafiltration. 100 g of L-tyrosine are dissolved in water using an ammonium solution. Tyrosine as a phenolic derivative is iodinated with elemental iodine, maintaining an alkaline pH. Iodinated tyrosines are separated from the aqueous iodide solution by repeated extraction with a 1: 3 ratio of butanol / ethyl alcohol. Next, the butanol-alcohol solution of iodotyrosine is dried on a rotary evaporator.

Example 9

As a drug for the prevention of damage to iodine radionuclides and the optimization of iodine metabolism in the post-prophylactic period, iodized goat milk casein containing iodine in covalently bound form is used, similar to natural human milk. Such iodinated white whites is suitable for enrichment of mixtures for baby food, including the type of "Baby" and "Baby." This is facilitated by a high degree of protein iodization and, therefore, small amounts of iodinated proteins necessary for enrichment of the mixtures, as well as high thermal stability of the covalent iodine compound, good solubility and low allergenicity.

The technology for producing iodized infant formulas includes the synthesis of goat milk iodinated casein according to Example 1, the introduction of iodized protein into cow's milk, homogenization of the milk base, vacuum condensation and spray drying.

The effectiveness of using iodized milk proteins as a source of iodine for infants is obvious, since the main form of iodine during natural feeding is its covalent compounds with breast milk proteins.

Example 10

A drug for the prevention of damage to iodine by radionuclides and optimization of iodine metabolism in the post-prophylactic period — iodinated peptides are obtained by partial enzymatic hydrolysis of casein previously iodinated in Example 1. The hydrolysis of the iodinated protein is carried out with trypsin or papain in a buffered solution at slightly alkaline pH values. Such a preparation has increased stability in the technological processes of the production of baby food or when baking bread products. In the production of bread, iodine-containing compounds are kneaded before adding flour. Forming a true solution, iodine-containing molecules are further uniformly distributed throughout the bread loaf, which ensures a normalized consumption of iodine. The amount of dietary supplement to food - iodinated peptides depends on the degree of radioiodine contamination in the region.

Example 11

A fat-soluble drug for the prevention of iodine radioactive damage is obtained on the basis of iodinated isoprene - carotene. Iodination is carried out on unsaturated bonds. Such a preparation is included in the composition of a vitamin complex containing lipids. Once in the body, the iodinated carotene derivative serves as a source of iodide for the thyroid gland. Iodide is released as a result of enzymatic catalysis.

Example 12

In example 1, carry out the synthesis of iodinated proteins. A wet tablet mixture is obtained consisting of a solution of iodinated protein (100 mg of covalently bound iodine per 250 mg tablet), lactose, starch, magnesium stearate. The operations of mixing, granulating, drying, dusting and pressing the tablet mass are performed. The resulting tablet contains 100 mg of physiologically effective covalently bound organic iodine. The tablet form of the drug allows for the individual prevention of radiation damage. This form of the drug is convenient for use in the field. The tablet form of the drug allows you to adjust the intake of iodine in the body, depending on age and physiological characteristics. The tablet form of the drug is suitable for long-term storage due to the chemical stability of the organic covalently bound form of iodine.

This example is a preferred embodiment of the invention.

Example 13

As a drug for the prevention of damage to iodine radionuclides and the optimization of iodine metabolism in the post-prophylactic period, iodized proteins and amino acids isolated from kelp are used. Iodine is in this preparation in covalently bound form. For a single dose, the drug is used in an amount exceeding the physiological norm of iodine by 100-1000 times.

Example 14

The drug for the prevention of iodine damage by radionuclides and the optimization of iodine metabolism in the post-prophylactic period is dried extracts of fucus containing inorganic iodide and covalently bound iodine in the composition of amino acids and proteins. The drug is normalized by the iodine content. It is used according to the traditional scheme, providing an excess of the stable iodine isotope in the body.

Example 15

As a drug for the prevention of damage to iodine by radionuclides and the optimization of iodine metabolism in the post-prophylactic period and the optimization of iodine metabolism in animals, iodized animal protein is used. The tyrosine-containing hemoglobin protein is iodinated chemically as described in Example 1. Iodine in such compounds is covalently bound in the 3 position of the phenolic ring of tyrosine amino acid residues. Iodization is carried out, preventing the condensation of iodinated tyrosines, with the formation of thyroid hormonal compounds, for which low iodization temperatures and a limited iodization time are used. The drug contains iodine in high concentration and is used in small quantities. The degree of drug iodization is regulated by the amount of iodine introduced and the time of iodination. An iodine-containing preparation is used to enrich dry or liquid feed.

The drug undergoes hydrolysis in the gastrointestinal tract with the release of iodine-containing amino acids. Iodine is absorbed as part of these amino acids. Unlike inorganic iodine compounds, covalently bound iodine as part of an amino acid is involved in the optimization of iodine metabolism, since it makes possible tissue deposition of iodine-organic compounds, their chemical modification, thereby involving the mechanisms of excretion of iodine and iodine from the body. Finally, iodinated amino acids act as an effective source of iodine as a result of tissue enzymatic cleavage of iodide, which enters the thyroid gland. Iodized protein is a stable preparation, stable during heat treatment, safe for the animal organism. The degree of feed iodization is determined by specific needs, age and physiological standards for iodine supply of the body.

Example 16

The preparation is a hydrolyzed iodinated egg albumin protein with covalently bound iodine, which is combined with organically bound iodine in a non-covalent form, for example, a compound with starch. The combination of iodine with starch acts as a source of inorganic iodine, while iodine is released in the intestines of the animal gradually and to a limited extent. Covalently bound iodine and inorganic iodine are absorbed through various mechanisms. Their further metabolism is different. This form of the drug accelerates the intake of iodine in various tissues and the thyroid gland of the animal, blocks the accumulation of the radioactive isotope in the mucous membranes of the gastrointestinal tract.

The egg albumin solution is iodinated in accordance with Example 1, except for the heat treatment step. Sterilization of the iodinated egg albumin solution is carried out by microfiltration. Preservation of the drug is provided by freeze-drying.

Example 17

The drug for the prevention of iodine damage by radionuclides and the optimization of iodine metabolism in the post-prophylactic period is a combination of organically bound iodine - iodized soy protein and inorganic compound iodine - potassium iodide. The drug uses alternative mechanisms of iodine absorption: in the composition of the iodinated amino acids tyrosine and histidine and in the form of a free anion of iodine - iodide. Such a preparation is used for feeding domestic and agricultural animals and birds, including it in the feed composition.

Example 18

The drug for the prevention of iodine damage by radionuclides and the optimization of iodine metabolism in the post-prophylactic period, containing iodine in covalently bound form in the form of iodinated unsaturated fatty acids - linoleic, linolenic and arachidonic in purified olive oil for injection, is intended for the prevention of damage to animals by radioactive iodine in the pasture period. Subcutaneous or intramuscular injection in an amount of 10-25 mg / kg of live weight has a prolonged effect and ensures the entry of a stable iodine isotope into the body of the animal for several months. A drug so implanted does not have a toxic effect.

Example 19

The drug for the prevention of damage to iodine by radionuclides and the optimization of iodine metabolism in the post-prophylactic period, containing organic covalently bound iodine in the form of a mixture of iodized soy protein hydrolyzate and iodinated isoprenes - lycopene and carotene, is applicable for the enrichment of premixes intended for feeding farm birds and animals. The drug is resistant to technological conditions for the preparation and storage of premixes. Derivatives of isoprenes iodine on unsaturated bonds.

Example 20

For laying hens, a feed is prepared containing 100 g of 17 g of crude protein, 11.72 MJ of metabolic energy and 3.2 g of calcium, and at the same time it is enriched with mineral components and vitamins.

As a source of iodine, its covalent organic compound is used, which is iodized egg albumin, which is characterized by a high tyrosine content. For iodination, albumin from notched chicken eggs is used. The protein is separated from the yolk and homogenized with an equal volume of a 4% sodium chloride solution. Iodination is carried out with a solution of iodine in potassium iodide, maintaining the temperature and alkaline pH of the reaction mixture with constant stirring. The end of iodination is determined by a qualitative reaction to the presence of elemental iodine. Iodide is removed by reprecipitation of iodinated albumin with acid. Resuspension of iodine-containing protein is carried out with 2% sodium chloride. The iodide-free solution is freeze-dried or spray dried. Such iodination allows you to get protein with more than 10% bound iodine. Dispersed protein is added with vitamins and minerals to the feed grain base (in an amount of 20 mg per 100 g of feed) and mixed thoroughly.

Iodized protein is stable in feed. Iodine enters the body as a component of a non-hormonal iodine-containing amino acid. The tissue enzyme deiodinase cleaves iodine at both the 3rd and 5th positions of the phenolic ring of tyrosine, supplying the thyroid gland with the necessary iodide. This example is a preferred embodiment of the invention.

Example 21

The drug for the prevention of damage to iodine radionuclides and the optimization of iodine metabolism in the post-prophylactic period is made in the form of granules or powders, as a component of vitamin-mineral complexes for animals and birds. As iodine-containing compounds, water-soluble iodine-containing polypeptide hydrolysates are used. Such a drug increases the effectiveness of radioprophylaxis.

Example 22. The prolonged form of the drug is a water-soluble iodine-containing substance - polished soy proteins, included in a durable dried agarose gel. The thermostability of BAFA allows it to be introduced into an agarose suspension and to obtain melts.

The agarose polymer matrix has steric limitations on the enzymatic hydrolysis of BACA in the gastrointestinal tract and the release of iodine-containing amino acids from the polymer matrix. This property of the drug prolongs the process of iodine absorption in the animal’s body, and allows increasing the amount of iodine administered.

Example 23

The water-soluble form of the drug, iodinated protein hydrolysates obtained from whey milk proteins, is suitable for enriching feed for young farm animals, for example calves, piglets. The use of liquid feed, such as milk substitutes, allows for the radioiodine prophylaxis of animals and ensures that iodine enters the body in the most adequate form.

Example 24

The drug for the prevention of iodine damage by radionuclides and the optimization of iodine metabolism in the post-prophylactic period, containing iodine in covalently bound form, which is a solution of iodinated tyrosine, is intended to provide iodine to animals in the pasture period by subcutaneous implantation. An implant containing diiodotyrosine synthesized in accordance with Example 8 is administered to cattle subcutaneously in an amount of 10 mg / kg live weight by bound iodine. The drug in the form of an implant provides a prolonged intake of iodine in the thyroid gland, does not have a negative effect on the animal's body.

Example 25

A fat-soluble drug, which is an iodinated unsaturated fatty acid - arachidonic acid, is used for introduction into a vitamin complex based on vegetable oil. Iodination of arachidonic acid is carried out on unsaturated bonds.

Example 26

According to example 1, the preparation of iodinated goat milk proteins is synthesized, excluding the canning stage. The drug provides additional prevention from the negative effects of radiation. After purification of the protein solution from iodides, the preparation is freeze-dried. The final moisture content of the drug is up to 3.5%. Goat milk proteins are less allergenic than cow proteins. The drug is included in the combined complex containing vitamins and minerals. 1 capsule contains vitamin B ₁ 5 mg, vitamin B ₆ 2 mg, vitamin B ₁₂ 1.5 mg, nicotinamide 5 mg, calcium pantothenate 2 mg, ascorbic acid 25 mg, iron 5 mg, copper 100 μg, zinc 100 μg, magnesium 3.5 mg, calcium 15 mg, phosphorus 10 mg, cobalt 100 μg, manganese 500 μg, molybdenum 200 μg, covalently bound organic iodine 10 mg.

Claims (12)

1. A method for the prevention of damage to iodine radionuclides of a human or animal organism, comprising administering an iodine-containing preparation into the body, characterized in that the preparation comprises an organic compound of iodine covalently bound to a substance selected from the group of carboxylic acids, unsaturated fatty acids, lipids, terpenes, terpenoids , isoprenes, peptides, polypeptides, amino acids, protein hydrolysates, polypeptide hydrolysates, proteins of plant, and / or animal, and / or microbiological origin, lipid mixtures b and unsaturated fatty acids, mixtures of isoprenes and terpenes, mixtures of isoprenes and protein hydrolysates, mixtures of isoprenes and unsaturated fatty acids, while proteins, peptides, polypeptides, amino acids, polypeptide and protein hydrolysates are chosen where iodine is covalently bound in 5 and 3 or in the 3 position of the phenolic cycle, and amino acids and proteins do not have hormonal thyroid activity, and a single dose of the product contains such an amount of iodine to provide a daily dose of iodine exceeding the physiological need for it in 100-1000 r az 2. The method according to claim 1, characterized in that caseins, egg albumin, milk or whey proteins, hemoglobins are used as animal proteins, and soy protein as plant proteins. 3. The method according to claim 1 or 2, characterized in that the preparation further comprises an organic compound with non-covalently bound iodine. 4. The method according to any one of claims 1 to 3, characterized in that the preparation further comprises inorganic iodine. 5. The method according to any one of claims 1 to 4, characterized in that the preparation is a prolonged form in the form of tablets, powders, capsules, microcapsules, dragees, solutions. 6. The method according to claim 5, characterized in that the microcapsules are obtained by microencapsulation using carbohydrate, protein or lipid raw materials. 7. The method according to any one of claims 1 to 6, characterized in that the preparation is included in an inert polymer matrix, for example, from carrageenan, pectin, agarose or uronic acids. 8. The method according to any one of claims 1 to 7, characterized in that when used in humans, the drug is included in the vitamin-mineral complex. 9. The method according to any one of claims 1 to 7, characterized in that when used in humans, the drug is included in a food product. 10. The method according to any one of claims 1 to 7, characterized in that when used in an animal, the preparation is a premix. 11. The method according to any one of claims 1 to 7, characterized in that when used in an animal, the preparation is part of the premix. 12. The method according to any one of claims 1 to 7, 10, 11, characterized in that when used in an animal, the preparation is part of the feed.