RU2328878C2 - Production method and biologically active food additive to prevent iodine deficiency and optimise iodine metabolism - Google Patents

Abstract

FIELD: food processing.

SUBSTANCE: invention relates to the biologically active food additive for prevention the iodine deficient conditions, optimisation of the iodine metabolism and the method for its production. The biologically active food additive can be used for producing the vitamin-mineral complexes or food products and drinks enriched with iodine and zinc. The biologically active additive is the organic molecules of casein which contain both iodine and zinc. The method for producing the additive includes adding the solution of the tetrasodium salt of the ethylene diamintetra-acetic acid to the casein solution; mixing and following diafiltration at the membrane device with the ultrafiltrating membrane with the cutoff limit 10-100 kD with use of 1.5-3% sodium chloride solution as a dialysing agent and maintaining the pH within 6.5-7.5 to obtain the purified solution of the activated casein. The obtained purified solution of the activated casein with concentration of 80-120 g/l is transferred to the reactor, brought to 35-40°C and under maintaining it, the simultaneous iodinating of the aromatic acids and saturation of the casein phosphoric groups with the zinc ions is performed, and the pH of the process is maintained within 6.5-7.5 with the help of sodium hydroxide solution. Then, the solution is repeatedly diafiltrated with the use of 1.5-3% sodium chloride at pH=6.5-7.5.

EFFECT: efficient control of iodine metabolism and usability.

8 cl, 1 tbl, 3 ex

Description

The invention relates to the food industry, and in particular to a biologically active food supplement for the prevention of iodine deficiency conditions, optimization of iodine metabolism, and a method for its production. A dietary supplement can be used for the preparation of vitamin-mineral complexes or food products enriched with micronutrients: iodine and zinc. In particular, a biologically active additive can be used in the production of bread, bakery, pasta and confectionery, dairy products, baby food, as well as various drinks: drinking and fruit water, beer, kvass.

It is known to use iodized food salt to compensate for the lack of iodine entering the body. The iodized salt is a mechanical mixture of ordinary salt (NaCl) and inorganic compounds of potassium iodide (KI) or potassium iodate (KIO ₃ ) (Monitoring Universal Salt Iodization Programs. Published by PAMM / ICCIDD / MI, 1995).

In the Russian Federation, iodized salt with an iodine content of 40 ± 15 μg per 1 g of product is used. It is extremely difficult to achieve uniform mixing at this ratio of components. In addition, inorganic salts of iodine are unstable and gradually decompose with the loss of iodine during storage and especially during heat treatment of food. Salt consumption rates are variable in different groups of the population and range from 0 (salt is contraindicated in certain diseases) to 10-15 g per day, while 375-825 mcg of iodine can enter the body, which is 2.5-5.5 times higher physiological norm. Exceeding the physiological intake of inorganic iodine can cause thyroid disease. The experience of using iodized salt for the prevention of iodine deficiency in Africa shows an increase in the frequency of iodinated thyrotoxicosis in the elderly (Problems of Endocrinology No. 4, 2005, T 51, p. 36).

Mineral compounds of iodine in vivo act as an auxiliary source of iodine, while the evolutionary mechanism of iodine metabolism is primarily aimed at using the organic form of iodine, which prevails in natural foods.

It is known to use a dry starch-iodide complex for the treatment or prevention of diseases caused by iodine deficiency (RU C1 No. 2110265, IPC 6 A61K 33/18, 1998). Iodine is in this complex mainly in the form of an inclusion compound, so this complex can be called a prolonged form of the inorganic iodine preparation, which is absorbed gradually, as the starch is digested in the gastrointestinal tract.

Thus, the use of starch-iodide complex does not allow the regulation of iodine metabolism, which is possible when using the organic form of iodine. In addition, this drug cannot be used as an additive to food subjected to cooking, since it begins to decompose at 40 ° C.

It is known to use a biologically active additive in the form of a complex compound of inorganic iodine and pectin for the prevention of iodine deficiency (RU C1 No. 2265377, IPC 7 A23L 1/30, 2005; RU C1 No. 2265376, IPC 7 A23L 1/30, 2005). In this case, there is also a complex compound of inorganic iodine, which is gradually absorbed as the pectin iodine complex moves along the gastrointestinal tract.

Individual adjustment of iodine metabolism in this case is also impossible. The use of this drug as an additive to food is extremely inconvenient, since it is a water-insoluble powder.

Known biologically active food supplement for the prevention of iodine deficiency based on fruits of mountain ash with pectin to stabilize the iodine content during storage of the drug (RU C1 No. 2271726, IPC 7 A23L 1/30, 03.20.2006).

The main disadvantage of this invention is the extremely low specific iodine content in the product: 70 μg per 100 g. In addition, since special measures are required to stabilize the iodine content during storage, a significant part of the iodine is in inorganic form.

Known food products, including iodine-containing food additives: bread, bakery products, milk, butter, meat products (Collection of recipes and technological instructions for the preparation of dietetic and prophylactic varieties of bakery products, State Research Institute of the Bakery Industry, Moscow, Pishcheproduct, 1997, Iodine-fortifying food supplement "Amiton", TU, TI, RC 9110-273-05747158-98). Inorganic compounds of iodine, kelp (seaweed), and yeast grown in iodized aqueous medium are used as food additives in these products.

A disadvantage of the known products is that in yeast when grown on iodized medium, the metabolism can change, and the products have a pronounced unpleasant aftertaste and smell. This is due to the decomposition of inorganic iodine compounds in the light with the release of free iodine. Seaweed also contains a large amount of inorganic iodine compounds, and the ratio of organic to inorganic forms of iodine varies greatly depending on the location and growing conditions, processing and transportation methods.

A known method of obtaining a biologically active food supplement for optimizing iodine metabolism, which is the germination of grain in water containing various trace elements: iodine, selenium, cobalt, molybdenum, zinc, copper, manganese in a certain concentration, drying the germinated grain, grinding and compounding it in various combinations (RU C1 No. 2271725, IPC 7 A23L 1/30, 03.20.2006).

The advantage of this method is that, along with iodine, concomitant micronutrients are introduced that improve the metabolism of iodine in the body. The disadvantage of this invention is that 20-50% of the average daily need for iodine is in 40-70 g of flour. Receiving such an amount daily is clearly inconvenient, and the low-tech production method does not allow replacing a significant part of the flour produced with its biologically active analogue.

Known biologically active food supplement obtained by enzymatic hydrolysis of animal protein - elastin - and iodination of the resulting hydrolyzate, followed by drying of the product (RU C1 No. 2266021, IPC 7 A23L 1/30, 2005). The daily rate of iodine contains 1-4 g of the resulting powder.

The disadvantage of this invention is the need to dissolve the powder before adding to food products, as well as changing the taste of the products. In addition, in this case, only iodine deficiency is compensated for, without the introduction of other micronutrients involved in its metabolism.

In a number of inventions, for the prevention of iodine deficiency, it is proposed to use a synthetic organic compound with covalently bound iodine selected from various groups of natural organic compounds, including proteins of plant, animal or microbiological origin and various mixtures thereof (RU C1 No. 2134520, IPC 6 A23J 1/20, 1999; RU C1 No. 2141205, IPC 6 A21D 2/02, 1999; RU C1 No. 2163127, IPC 7 A61K 33/18, 2001; RU C1 No. 2192150, IPC 7 A23L 1/304, 2002).

The advantage of this proposal is the lack of hormonal activity of the obtained synthetic organic compounds and the ease of their addition to food products. The disadvantages include the use of xenobiotics for the synthesis, such as chloramine T, iodine chloride or iodine trichloride. Special measures are needed to control their absence in the final product. In this case, trace elements accompanying iodine are also not introduced.

A known method for producing iodized protein (RU C1 No. 2188648, IPC 7 A61K 33/18, 2002) and a means for regulating iodine metabolism or prevention of iodine deficiency conditions (RU C1 No. 2151611, IPC 7 A61K 38/16, 2000), where iodine protein is offered adding to the solution of the protein an iodinating agent - iodine chloride, dissolved in hydrochloric or acetic acid. As a result, iodine joins to the aromatic rings of amino acids - tyrosine, phenylalanine and tryptophan. During the reaction, the pH of the solution decreases and a precipitate of iodinated protein forms, which is separated by centrifugation or filtration and then dried. The resulting product, characterized in that it contains iodinated protein or its low molecular weight component, the structure of which includes at least one of the following amino acids - phenylalanine, tryptophan. In the particular case, it is proposed to use milk protein - casein for iodination.

When using this tool, an overdose is impossible, since in the gastrointestinal tract the iodized protein decomposes to iodinated amino acids, which enter the liver. In the liver, iodine is cleaved from them under the influence of an enzyme, deiodinase, the activity of which depends on the degree of iodine deficiency and the functional state of the thyroid gland. Excessive amount of iodinated amino acids, turning into glucuronides, leaves the body.

The disadvantage of these inventions is the use of chlorine iodide to obtain iodinated protein (an admixture of this xenobiotic in the final product is possible). The finished form in the form of a powder is not always convenient for addition to food products - an additional stage of dissolution is necessary. This tool introduces only iodine into the body, and this is not always enough to regulate iodine metabolism, especially at the initial stage of correction of iodine deficiency states.

The technical result of the invention is to obtain a biologically active food supplement for the prevention of iodine deficiency and optimization of iodine metabolism, which provides effective regulation of iodine metabolism, including at the initial stage of relief of iodine deficiency due to the presence of zinc, which can be diluted with water and convenient for this reason when using for the enrichment of foods with iodine and zinc.

This technical result is provided by a biologically active food supplement for the prevention of iodine deficiency conditions and the optimization of iodine metabolism, made in the form of casein containing both iodine and zinc in organic molecules.

A method of producing said biologically active additive involves adding a solution of ethylenediaminetetraacetic acid tetrasodium salt to a casein solution, mixing them and then diafiltering on a membrane unit with an ultrafiltration membrane with a cut-off limit of 10-100 kD using a 1.5-3% sodium chloride solution as a dialysis solution while maintaining a pH in the range of 6.5-7.5 to obtain a purified solution of activated casein, then the resulting purified solution of activated casein at the end By nitration, 80-120 g / l is transferred to the reactor, the temperature of the solution is brought to 35-40 ° C and, while maintaining it, the iodination of aromatic amino acids and the saturation of casein phosphorus groups with zinc ions are carried out, maintaining the process pH in the range of 6.5-7.5 using a solution of sodium hydroxide, then the solution is subjected to repeated diafiltration using a 1.5-3% NaCl solution at a pH of 6.5-7.5 to obtain the finished product in the form of a concentrated casein solution containing iodine and zinc in the composition of the molecules.

During the first diafiltration, the phosphoether groups of casein are released from calcium ions and other divalent metals and are activated. In this case, the product is washed from the ions of heavy metals (lead, cadmium, copper, etc.) that can be present in it, as well as lactose and other low molecular weight compounds.

Skim milk may be used as a casein solution.

In the best embodiment of the invention, a saturated solution of fine crystalline iodine in a solution of potassium iodide is used for iodination of aromatic amino acids, and a solution of a water-soluble zinc salt is used to saturate the phosphorus groups of casein with zinc ions.

An equimolar amount of zinc salt is taken per 1 mol of phosphate in casein, since casein contains about 1% phosphorus (S.I. Athonsky. Animal Biochemistry. Moscow, Higher School, 1970, pp. 1339, 570-575).

As a water-soluble zinc salt, zinc sulfate, chloride or zinc iodide is generally used.

The solution obtained after repeated diafiltration can be subjected to preservation by the addition of 50% sucrose, fructose, glycerol or propylene glycol. The product containing preservatives can be pasteurized by brief heating to 90 ° C.

The possibility of carrying out the invention is illustrated by the following examples.

Example 1

100 g of casein was dissolved in 3 L of phosphate buffer (0.1 M, pH 7.5), 60 ml of 0.5 N EDTA solution was added, mixed and subjected to a Millipore Polysulfone Membrane Pellicon-2 Ultrafiltration Unit with a retention limit of 100 cd.

The solution was concentrated to 1 L and washed on the membrane with 10 L of a 3% NaCl solution prepared in deionized water, the feed rate of the washing solution being equal to the filtrate discharge rate.

The washed concentrate was transferred to the reactor, the temperature was maintained equal to 36 ± 1 ° C.

The reaction solution was prepared as follows. 40 g of potassium iodide, 10.8 g of zinc iodide were dissolved in 300 ml of deionized water, then 45 g of finely crystalline iodine was added to the solution with vigorous stirring on a magnetic stirrer.

The reaction solution was added in small portions to the reactor, maintaining by means of a titrimetric system a pH value in the range of 6.5-7.5.

After completion of iodination and saturation of the phosphorus groups with zinc ions, the solution was subjected to diafiltration washing on a membrane unit using 10 L of a 3% NaCl solution.

The result is 895 g of a solution containing in its composition: 10.2% protein, 0.9% iodine and 0.25% zinc.

Example 2

They took 228 liters of whole milk, skimmed the milk on a separator and transferred it to the capacity of a Biokon industrial ultrafiltration unit with cellulose acetate membranes with a cut-off limit of 10 kD (milk pH is 6.6).

4.5 L of a 0.5 N EDTA solution was added to the solution, mixed, concentrated to 75 L, the concentrate was diluted in a container to 250 L with a 1.5% NaCl solution in deionized water, and the concentration was repeated.

Washing on the membrane as described above was done seven times.

The washed concentrate with a volume of 82 l was transferred to an industrial reactor, the temperature was adjusted and maintained during processing in the range of 36-40 ° C.

To prepare the reaction solution, 3 kg of potassium iodide, 360 g of anhydrous zinc sulfate were dissolved in 20 l of deionized water, and then 3 kg of finely crystalline iodine was added. The resulting solution was added in small portions to the washed milk protein concentrate, maintaining the pH of the reaction mixture in the range of 6.5-7.5.

After washing seven times with a 1.5% solution of sodium chloride in deionized water, as described above, 71 kg of concentrate were obtained.

For preservation, 71 kg of glycerol was added and pasteurized at 90 ° C for 20 minutes.

The resulting product contained 4.12 mg / g of iodine and 1.23 mg / g of zinc.

Example 3

For processing, they took 108 l of whole milk, degreased on a separator and subjected to diafiltration washing on a cellulose acetate membrane with a retention limit of 20 kD.

2.2 L of a 0.5 N EDTA solution was added to skim milk, mixed and concentrated to 32 L, then the concentrate was diluted to 120 L with a 2% NaCl solution in deionized water (pH 6.8).

Concentration - dilution was carried out seven times. The washed concentrate with a volume of 36 L was transferred to the reactor; the temperature was maintained at 38 ± 2 ° C.

The reaction solution was prepared by dissolving in 10 l of deionized water 1.5 kg of potassium iodide, 150 g of zinc chloride and 1.5 kg of iodine. This solution was added to the reactor, maintaining the pH in the range of 6.5-7.5 with a NaOH solution.

Next, the processed protein concentrate was washed on the membrane 7 times with a 2% NaCl solution.

34.4 kg of concentrate were obtained, 35 kg of sugar was added to it with stirring.

Pasteurized at 90 ° C for 30 minutes

The resulting product contained 3.86 mg / g of iodine and 1.18 mg / g of zinc.

The advantages of the proposed biologically active additives were confirmed in experiments in vivo, in laboratory animals.

Experimental hypothyroidism was simulated using thyamazole thyrostatics for 14 days. Then, also for 14 days, the test additive was orally administered to one group of animals, iodine casein was administered to the other group of animals, based on the weight of the animals and taking into account the rate of metabolic processes.

The biological effectiveness of the supplement was evaluated by the level of hormones (thyroxine T4, triiodothyronine T3 and thyrotropic hormone TSH) in the blood serum of animals by enzyme-linked immunosorbent assay.

As a result, the following data were obtained: thiamazole reduces the level of T4 hormones by 2 times, T3 by 17 times, and the content of the pituitary thyroid stimulating hormone increases by more than 2 times relative to their content in the blood of the intact group.

The results of the treatment of experimental hypothyroidism with iodcasein or the proposed dietary supplement are presented in the table.

The level of thyroid hormones in the blood serum of animals with experimental hypothyroidism (M ± m) Group 10th day 12th day 14th day T4 nmol / L T3 nmol / L TTG mE / L T4 nmol / L T3 nmol / L TTG mE / L T4 nmol / L T3 nmol / L TTG mE / L intact 98.2 ± 9.46 1.36 ± 0.04 0.75 ± 0.03 101.16 ± 8.41 1.40 ± 0.05 0.81 ± 0.04 99.56 ± 8.56 1.39 ± 0.04 0.78 ± 0.03 tiamazole 47.52 ± 6.64 0.08 ± 0.01 1.64 ± 0.12 iodine casein 68.34 ± 541 1.64 ± 0.05 0.46 ± 0.04 81.53 ± 7.58 1.52 ± 0.04 0.58 ± 0.03 94.42 ± 9.14 1.28 ± 0.06 0.64 ± 0.08 casein with I and Zn2 + 92.54 ± 8.34 1.27 ± 0.04 0.85 ± 0.06 102.23 ± 5.14 1.38 ± 0.06 0.78 ± 0.05 101.26 ± 5.87 1.36 ± 0.03 0.75 ± 0.07 Note: significance between groups p <0.05

As can be seen from the data presented in the table, the content of triiodothyronine is primarily compensated, and in the case of iodine casein with an excess of hormone levels in the intact group of 20% on the 10th day of therapy, 9% on the 12th day of therapy and only on 14 The day is reduced to approximately the level of that in the intact group.

The level of T4 hormone is slowly restored to normal: on the 10th day, 70% of the level of the control group, on the 12th day, 80% and only on the 14th day it reaches 95% of the level in the intact group.

Since the pituitary gland contains receptors only on TK, the level of thyroid stimulating hormone (TSH) in the blood of experimental animals is reduced and is restored only on the 14th day.

If the proposed dietary supplement (casein with iodine and zinc) is used on the 10th day of therapy, the T3 level is 93% of the norm, the T4 level is 94% of the norm and already on the 12th day the hormone levels are completely normalized. This effect can be explained by the fact that when iodine-containing hormones appear in the body, the metabolic rate increases, in particular the oxidative breakdown of fats and carbohydrates (Y.Kh. Tarakulov. The thyroid gland, in the book Physiology of the Endocrine System, edited by Baranov V.G. ., Leningrad, Science, 1979, pp. 135-184). Oxidative decomposition is accompanied, in turn, by an increase in the content of superoxide radicals in the tissues of the body that inhibit thyroperoxidase. Activation of the oxidative process causes an increase in the production of less iodinated T3 hormone and a decrease in more iodinated T4, these shifts are caused by a violation of the iodine organization processes in thyrocytes, which is possible at the stage of iodine oxidation by thyroperoxidase (Fukayama N., Murakami S., Nasu M., Sugawara M. / / Thyroid. - 1991. Vol 1, No. 3, p. 267-271).

In the case of simultaneous intake of zinc ions with iodine, which is a co-factor of enzymes - superoxide dismutases, there is no increase in the level of superoxide radicals, since the physiological function of superoxide dismutases is the inactivation of superoxide radicals.

Thus, the restoration of the normal level of thyroid-stimulating hormones in the blood of laboratory animals after experimental hypothyroidism using the proposed dietary supplement occurs 2 days earlier than when using iodine casein, and this restoration occurs without changing the ratio of hormones at the initial stage of therapy.

Claims (8)

1. A biologically active food supplement for the prevention of iodine deficiency conditions and the optimization of iodine metabolism, made in the form of casein containing both iodine and zinc in organic molecules. 2. A method of obtaining a biologically active food supplement for the prevention of iodine deficiency conditions and optimization of iodine metabolism according to claim 1, comprising adding a solution of ethylenediaminetetraacetic acid tetrasodium salt to casein solution, mixing them and subsequent diafiltration on a membrane unit with an ultrafiltration membrane with a cut-off limit of 10-100 KD and using as a dialysis solution a 1.5-3% sodium chloride solution while maintaining a pH in the range of 6.5-7.5 to obtain a purified solution of activated casein, then the obtained purified solution of activated casein with a concentration of 80-120 g / l is transferred to the reactor, the solution temperature is brought up to 35-40 ° C and, while maintaining it, the aromatic amino acids are simultaneously iodized and casein phosphorus groups are saturated with zinc ions, maintaining pH process in the range of 6.5-7.5 with a solution of sodium hydroxide, then the solution is subjected to repeated diafiltration using a 1.5-3% NaCl solution at a pH of 6.5-7.5 to obtain the finished product in the form of concentrated solution casein containing iodine and zinc in the composition of the molecules. 3. The method according to claim 2, characterized in that skim milk is used as a casein solution. 4. The method according to claim 2, characterized in that for the iodination of aromatic amino acids of casein, a saturated solution of fine crystalline iodine in a solution of potassium iodide is used. 5. The method according to claim 2, characterized in that for the saturation of the phosphorus groups of casein with zinc ions, a solution of a water-soluble zinc salt is used, and an equimolar amount of zinc salt is taken per 1 mol of phosphate contained in casein. 6. The method according to claim 5, characterized in that either a sulfate, or chloride, or zinc iodide is used as the water-soluble zinc salt. 7. The method according to claim 2, characterized in that the solution obtained after repeated diafiltration is preserved by the addition of 50% sucrose, fructose, glycerol or propylene glycol. 8. The method according to claim 7, characterized in that the product containing preservatives is subjected to pasteurization by short-term heating to 90 ° C.