RU2475262C1 - Complex immunomodulatory medication for prevention of malfunctions and regulation of immune system functioning (versions) - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine and deals with complex immunomodulator for prevention of malfunctions and regulation of immune system functioning (versions). Claimed is complex medication for prevention of malfunctions and regulation of immune system functioning, which is characterised by the fact, that it is made in form of capsules and contains human recombinant interferon of alpha, and/or beta, and/or gamma types, retinol palmitate, zinc sulphate monohydrate, additional substance - to 0.1 g. Also claimed is complex immunomodulator for prevention of malfunctions and regulation of immune system functioning, which is characterised by the fact that it is made in form of suppository on hydrophilic base and contains human recombinant interferon of alpha, and/or beta, and/or gamma types, retinol palmitate and/or substances, selected from a number of alpha, beta, gamma carotenes, zinc sulphate monohydrate, as well as additional substances.

EFFECT: invention insures extension of possibilities of prevention and correction of immunological malfunctions in healthy and ill people.

6 cl, 8 ex, 8 tbl

Description

Integrated immunomodulating agent for the prevention of disorders and regulation of the immune system (options).

The invention relates to medicine and relates to the creation of a pharmacological agent used to prevent disorders and regulate the immune response.

Anthropogenic environmental pollution, a significant deficiency of vitamins and minerals in nutrition, often unreasonable use of antibacterial agents, increased stress in everyday life, an increase in the frequency of the pathological course of pregnancy and childbirth, a significant prevalence of chronic diseases and urogenital infections in women of reproductive age - all this is an incomplete list factors that can lead to transient or persistent shifts in the functioning of the main parts of the immune system healthy and more flax person.

Traditionally, for the correction of immunity, drugs are used that are similar in composition to natural human defense factors, as well as exogenous or chemical substances that differ significantly from human immune defense factors. Currently, all three groups of immunomodulators of this kind are presented on the pharmaceutical market.

Among the used immunomodulators, preparations containing a combination of vitamin A and zinc (Zn) are practically not positioned. At the same time, there are a large number of multicenter blind placebo-controlled studies that indicate their direct and indirect positive effects on factors of nonspecific protection, cellular, humoral immunity, including local. A positive effect of vitamin A and zinc on physiological proliferation, regeneration of cells of the mucous membranes and skin is noted, which is considered as non-specific resistance factors, including anti-infection. In addition, zinc and vitamin A are powerful antioxidants that can protect cells from destruction due to damage or inflammation. A positive effect of these micronutrients on reproductive function, the visual analyzer, the work of the brain, and organs of the endocrine system is noted. Zinc is necessary for the operation of all enzyme systems, which determines its significant effect on all types of metabolism, DNA methylation and many other vital processes.

Known agent with immunomodulating, antimicrobial, antioxidant and regenerating effects (Pat. RF №2255760, class A61K 38/21, publ. 10.07.2005). The present invention provides a drug and its variants in the form of various dosage forms for oral, parenteral and external use (tablets, sprays, solutions, gels), for administration to mucous membranes (suppositories) based on natural and recombinant interferons such as α, β , γ, lysozyme and emoxipin.

Emoxipin in this tool acts as an antioxidant. However, these properties of emoxipin are manifested mainly in conditions of hypoxia.

In addition, the disadvantages of this invention are the use in a hydrophilic base for suppositories of such an unstable component as gelatin and a chlorhexidine preservative, which can reduce the stability of interferon. The tablet form of this oral product contains a large amount of lactose (0.3 g). As you know, lactose in many patients causes digestive disorders due to reduced activity or the absence of the corresponding enzyme, lactase. In the manufacture of a drug in the form of a tablet, interferon can be destabilized, since when tabletting under pressure, a significant increase in temperature occurs.

Known stabilized immunocorrecting drug viferon forte for the treatment of infectious and inflammatory diseases with a high degree of bioavailability, created on the basis of interferon human recombinant alpha and / or beta and / or gamma types with an antioxidant complex including tocopherol acetate, ascorbic acid and their derivatives as well as containing auxiliary substances: stabilizers, buffers, acids, plasticizers, emulsifiers, preservatives and base. (Pat. Russian Federation No. 2381812, class A61K 38/21, publ. 02.20.2010).

This tool has antibacterial, antiviral properties and is used in the treatment of infectious and inflammatory diseases of the urogenital tract, viral hepatitis, and other infectious pathologies.

In this tool, the specific activity of interferon is significantly increased due to the presence of antioxidants. It has been proven that the immune response to infection is usually accompanied by the activation of free radical oxidation. Therefore, it is believed that immunomulatory drugs, such as interferons, should be combined with antioxidants that suppress the excessive formation of free radicals.

In this tool, only IFN-alpha-2b has a direct immunomodulating effect. The antioxidants used in its composition - the vitamin complex of alpha-tocopherol acetate, ascorbic acid and their derivatives - do not have the property of a direct effect on the links of the immune system.

Their properties are mainly aimed at reducing the content of peroxidation-free radical products in the body. They have an indirect effect on the immune system, which limits the possibility of their use for the treatment and prevention of adverse outcomes of infectious and inflammatory diseases. The absence of the specific immunotropic effect of the antioxidant complex on the cells of the immune system significantly reduces the ability of the drug to modulate the immune system.

In addition, in this tool as a basis, various fats and oils are proposed that require special stabilization with a wide range of various substances.

The disadvantage of the above funds is the introduction of preservatives, such as chlorhexidine (disinfectant), which is not physiological for such a dosage form as suppositories.

The objective of the present invention is:

firstly, the creation of a complex immunotropic agent with a wide spectrum and the ability of polymodal action on different parts of the immune system, obtained on the basis of interferon human recombinant alpha, and / or beta, and / or gamma types and antioxidants-immunomodulators - retinol palmitate and / or substances selected from alpha, beta, gamma carotenes and zinc sulfate monohydrate. It is known that retinol palmitate and / or substances selected from alpha, beta, gamma carotenes and zinc sulfate monohydrate possess antioxidant properties and have a direct effect on all parts of the immune system. This significantly expands the range of therapeutic effects of the drug, including the possibility of using it to prevent complications and relapses of infectious and inflammatory diseases, especially in people with deficient conditions;

secondly, the choice of excipients that perform an active function. For example, substances that affect the pharmacological effect, ensure the stability of interferon, prevent its aggregation;

thirdly, the selection of optimal combinations and ratios of chemically and physiologically acceptable excipients necessary for a particular dosage form to create pharmaceutical compositions in the form of a dosage powder in capsules for oral administration and a dosage form in the form of suppositories for rectal administration to the mucous membranes;

fourthly, ensuring the stability and high bioavailability of active substances based on the manufacturability of the preparation (dosage forms) with the necessary pharmaceutical properties: mass uniformity, flowability, lack of caking, microbiological purity, etc.

To solve the tasks proposed variants of a comprehensive immunomodulating agent for the prevention of disorders and regulation of the immune system, made in the form of suppositories and capsules.

Option 1. A comprehensive tool is proposed for the prevention of disorders and regulation of the immune system, characterized in that it is made in the form of capsules and contains human recombinant interferon alpha and / or beta and / or gamma types, retinol palmitate, zinc sulfate monohydrate, auxiliary substance - up to 0.1 g

Human recombinant interferon α, and / or β, and / or γ types 250 thousand-1.0 million ME Retinol palmitate and / or substances selected from among alpha, beta, gamma carotenes 1.65-3.3 thousand ME Zinc sulfate monohydrate 0.0075-0.015 g Excipients up to 0.1 g

In this complex product, corn starch is used as the basis, hydroxypropyl cellulose, colloidal silicon dioxide and magnesium stearate are used as technological additives, in the amount of components: corn starch 0.075-0.085 g, hydroxypropyl cellulose 0.0015-0.0025 g, colloidal silicon dioxide 0 , 0001-0,0005 g, magnesium stearate 0,0005-0,001 g.

Option 2. A complex immunomodulating agent is proposed for the prevention of disorders and regulation of the immune system, characterized in that it is made in the form of suppositories on a hydrophilic basis and contains human recombinant interferon alpha and / or beta and / or gamma types, retinol palmitate and / or substances selected from alpha, beta, gamma carotenes, zinc sulfate monohydrate, as well as auxiliary substances in grams with the following ratios of components:

Human recombinant interferon α, and / or β, and / or γ types 125 thousand-1.0 million ME Retinol palmitate and / or substances selected from among alpha, beta, gamma carotenes 1.1-3.3 thousand ME Zinc sulfate monohydrate 0.005-0.015 g Excipients up to 1.5 g

In this case, polyethylene oxide 1500 and polyethylene oxide 400 are used as the basis of suppositories in a ratio of 10: 1; as a stabilizer - ethylenediaminetetraacetic acid sodium salt and polysorbate 80 (tween 80) in the amount of: ethylenediaminetetraacetic acid sodium salt 0.0002-0.005 g; polysorbate 80 (tween 80) 0.02-0.04 g; polyethylene oxide 1500 1.25-1.3 5 g; polyethylene oxide 400 0.1-0.2 g; purified water 0.002-0.003 g.

Vitamin A, retinol palmitate or other substances selected from the group of alpha, beta, gamma carotenes, in addition to antioxidant action, have pronounced immunomodulating properties and are able to stimulate the production of antibodies (humoral immunity). In addition, they guarantee the structural integrity of secretory immunoglobulin A (sIgA), which protects the mucous membranes from bacterial, food antigens, and prevents the penetration of foreign antigens into the internal environment of the body. It is proved that in conditions of vitamin A deficiency, these protective processes are slowed down or not implemented.

Thus, in conditions of vitamin A deficiency, a normal level of local immunity and its functioning in normal conditions and in diseases are not ensured.

Zinc provides the work of all enzyme systems, its ability to influence metabolism, DNA methylation and many other vital metabolic processes is noted, that is, it has the property of exerting a polymodal effect on the immune system.

Thus, in addition to antioxidant properties, interferon, vitamin A, and zinc sulfate in the complex exhibit synergism when exposed to all parts of the immune system.

When developing a dosage form in the form of rectal suppositories, the main matrix for interferon was selected hydrophilic polyethylene oxides, which, due to the polymer long-chain structure, are capable of ensuring the stability of interferon and the necessary adhesive-tropic properties to the mucous membrane. Polysorbate 80 (tween 80) and disodium salt of ethylenediaminetetraacetic acid stabilize interferon from aggregation, which is important for this type of drug.

Excipients, such as hydroxypropyl cellulose, colloidal silicon dioxide, magnesium stearate, corn starch, ensure the stability of interferon and the manufacturability of the manufacture of a solid dosage form in powder form in capsules.

Specific embodiments of the invention:

Example 1

Capsule preparation

30 g of corn starch and 1.46 g of palmitate retinol are loaded into a flask with a mixer, the mass is thoroughly mixed, then a homogeneous mixture of 41.62 g of corn starch and 13.36 g of zinc sulfate is added, and the mass is mixed.

In a separate flask, a solution of 35 ml of ethyl alcohol and 1.8 g of hydroxypropyl cellulose is prepared, the mass is thoroughly mixed until a solution is obtained, 1.0 ml (400 million IU) of interferon alpha-2b is added to the solution, the mass is thoroughly mixed, then the resulting solution with interferon with stirring, gradually added to a dry mixture of corn starch with retinol palmitate and zinc sulfate. Evenly moistened mass is granulated, the granules are dried at a temperature not exceeding 30-35 ° C. A mixture of 0.24 g of colloidal silicon dioxide and 0.55 g of magnesium stearate is added to the dried granules, the granules are thoroughly mixed. The obtained granular powder is loaded into capsules No. 3 of 0.1 g each. 800 capsules are obtained containing in each capsule of interferon alpha-2b recombinant human 500 thousand IU, retinol palmitate 3.3 thousand IU, zinc sulfate 0.015 g.

The resulting capsules meet the requirements of the Global Fund XI ed. and GF XII ed. (table 1).

Example 2

Capsule preparation

Into a flask with a stirrer load 0.5 ml (200 million IU) of interferon alpha-2b; 0.073 g of retinol palmitate; 7.5 g of zinc sulfate, 0.075 g of corn starch and 1.5 g of hydroxypropyl cellulose. Get 800 capsules containing in each capsule of interferon alpha-2b recombinant human 250 thousand IU, retinol palmitate 1,65 thousand ME, zinc sulfate 0,0075,

The resulting capsules meet the requirements of the Global Fund XI ed. and GF XII ed. (table 1).

Example 3

Capsule preparation

Into a flask with a stirrer, 2 ml (800 million ME) of interferon alpha-2b, 1.46 g of retinol palmitate, 13.36 g of zinc sulfate monohydrate, 0.075 g of corn starch and 2.5 g of hydroxypropyl cellulose are loaded. Get 800 capsules containing in each capsule of interferon alpha-2b recombinant human 1 million ME, retinol palmitate 3.3 thousand ME, zinc sulfate monohydrate 0.015 g

The resulting capsules meet the requirements of the Global Fund XI ed. and GF XII ed. (table 1).

The results of the analysis of the dosed mixture in capsules with interferon alpha-2b and retinol palmitate are presented in table 1.

Table 1 Indicator Norm Example 1 Example 2 Example 3 1. Description of the contents of the capsules White or almost white powder White powder White powder Almost white powder 2. The quantitative content of interferon alpha-2b 500 thousand ME 250 thousand ME 1 million 3. The quantitative content of retinol palmitate 3, 3 thousand ME 1.65 mg 3.3 thousand ME 4. Dissolution (release) Not less than 75% in 30 minutes 80% 83% 85% 5. Microbiological purity Compliance with the requirements of the Global Fund XII ed. Compliance with the requirements of GFHP ed. Compliance with the requirements of the Global Fund XII ed. Compliance with the requirements of GFHP ed. 6. Stability At 20 ° C 2 years 2 years 2 years

Example 4

Preparation of suppositories.

0.24 g of retinol palmitate and 2.5 g of tween 80 are loaded into the homogenizer, the mixture is thoroughly triturated at 20 ° C until a homogeneous mass is obtained. 15.5 g of polyethylene oxide 400 are added to the mass and mixed until homogeneous, then 0.02 g of disodium salt of ethylenediaminetetraacetic acid is added and mixed until completely dissolved, 1.5 g of zinc sulfate monohydrate is added, thoroughly homogenized and heated to 48-50 ° C. . To the resulting homogeneous suspension, 0.14 ml (50 million IU) of interferon alpha-2b, 0.2 ml of purified water are poured with stirring, the mass is thoroughly mixed and gradually poured with thorough stirring into 130 g of polyethylene oxide 1500, the mass is thoroughly mixed and quickly poured in blister strip packaging No. 5. Get 100 suppositories weighing 1.5 g, containing in each suppository 500 thousand IU of interferon alpha-2b, 3.3 thousand IU of retinol palmitate, 0.015 g of zinc sulfate monohydrate.

The resulting suppositories in terms of quality meet the requirements of the Global Fund XI ed. and GF XII ed. (table 2).

Example 5

Preparation of suppositories

0.034 ml (12.5 million IU) of interferon alpha-2b is loaded into the homogenizer; 0.08 g of palmitate retinol, 0.5 g of zinc sulfate monohydrate; 0.02 g of disodium salt of ethylenediaminetetraacetic acid; 2.0 g of tween 80; 10 g of polyethylene oxide 400; 135 g of polyethylene oxide 1500 and 0.05 ml of purified water. Get 100 suppositories weighing 1.5 g, containing in each suppository 125 thousand IU of interferon alpha-2b; 1.1 thousand IU of retinol palmitate; 0.005 g of zinc sulfate monohydrate.

The resulting suppositories in terms of quality meet the requirements of the Global Fund XI ed. and GF XII ed. (table 2).

Example 6

Preparation of suppositories

0.041 ml (15 million IU) of interferon alpha-2b is loaded into the homogenizer; 0.08 g of retinol palmitate; 0.5 g of zinc sulfate; 0.03 g of disodium salt of ethylenediaminetetraacetic acid; 2.5 g of tween 80; 15.2 g of polyethylene oxide 400; 130 g of polyethylene oxide 1500 and 0.03 ml of purified water. Get 100 suppositories weighing 1.5 g, containing in each suppository 150 thousand IU of interferon alpha-2b, 1.1 thousand IU of retinol palmitate, 0.005 g of zinc sulfate.

The resulting suppositories in terms of quality meet the requirements of the Global Fund XI ed. and GF XII ed. (table 2).

Example 7

Preparation of suppositories

0.25 ml (100 million IU) of interferon alpha-2b is loaded into the homogenizer; 0.24 g of retinol palmitate; 1.5 g of zinc sulfate; 0.04 g of disodium salt of ethylenediaminetetraacetic acid; 4.0 g Tween 80; 20 g of polyethylene oxide 400; 125 g of polyethylene oxide 1500 and 0.3 ml of purified water. Get 100 suppositories weighing 1.5 g, containing in each suppository 1 million IU of interferon alpha-2b, 3.3 thousand IU of retinol palmitate, 0.015 g of zinc sulfate.

The resulting suppositories in terms of quality meet the requirements of the Global Fund XI ed. and GF XII ed. (table 2).

Example 8

Preparation of suppositories

0.25 ml (100 million IU) of interferon alpha-2b is loaded into the homogenizer; 0.24 g beta carotene; 0.75 g of zinc sulfate; 0.04 g of disodium salt of ethylenediaminetetraacetic acid; 4.0 g Tween 80; 20 g of polyethylene oxide 400, 125 g of polyethylene oxide 1500 and 0.3 ml of purified water. Get 100 suppositories weighing 1.5 g, containing in each suppository 1 million IU of interferon alpha-2b, 3.3 thousand IU of retinol palmitate, 7.5 mg of zinc sulfate.

The resulting suppositories in terms of quality meet the requirements of the Global Fund XI ed. and GF XII ed.

The results of the analysis of the dosed mixture in rectal suppositories with interferon alpha-2b and retinol palmitate are presented in Table 2.

In accordance with current requirements, preclinical toxicological studies of a complex immunomodulating agent were performed. The program of preclinical toxicological studies included the study of the toxicity and tolerability of the drug with a single administration to laboratory animals, the study of the toxicity of its substance and finished dosage form in a chronic experiment in rats and dogs. In addition, a study was carried out of potential mutagenic, embryotoxic, teratogenic, allergenic and immunotoxic properties of the drug, and its effect on reproductive function was also investigated.

In a chronic experiment with 3-month intragastric administration to rats of the drug substance in doses of 0.03 and 0.06 g / kg and with a 4-week administration of the drug in the finished drug form in the stomach (0.1 g capsules for oral administration) at a dose of 0.03 g / kg, the drug is well tolerated by animals and does not cause toxic damage to internal organs, does not have a local irritant effect, which was confirmed by pathomorphological studies. The drug is not mutagenic in the Ames test and does not cause an increase in the number of chromosomal aberrations in bone marrow cells and dominant lethal mutations in mice.

The drug does not exhibit allergenic, immunotoxic, embryotoxic and teratogenic properties, and also does not adversely affect the reproductive function of animals.

A study of the immunomodulating action of a new complex immunomodulating agent. The results of the study are presented in tables 3-8.

In vitro experiments studied the effect of the drug on the cells of innate immunity, adaptive immunity and the cytokine network. It was proved that the drug significantly enhances NK activity (Table 3), increases the expression of costimulation molecules by myeloid dendritic cells-SD80, SD86 (Tables 4, 5), dose-dependently inhibits PHA-induced proliferation of T-lymphocytes in a wide range of concentrations (1- 1000 U / ml) - (Table 6), induces the production of TNF (Table 7), in an experiment on experimental animals - at a dose of 50 μg / mouse, enhances the B-cell response (Table 8).

At a concentration of 100 and 1000 U / ml (according to interferon-alpha) of a complex immunomodulating agent, it significantly increases the activity of natural killers (natural killer-NK).

Table 3 The number of K-562 target cells killed during 4 hours of incubation with donor mononuclear cells (MNCs) cultured for 24 hours in the presence of the drug (%) Donor number The drug (units / ml) 0 10 one hundred 1000 one 29.5 31.6 26.0 38.6 2 47.4 57.9 65 61,4 3 70.8 68.7 81.9 83.7 four 46.5 55.3 65,4 72.0 5 49.2 61.0 73.8 65,2 M ± σ 48.7 ± 31.4 54.9 ± 24.7 62.4 ± 38.5 ** 64.2 ± 29.4 ** ** p <0.01 compared with the killer activity of MNCs incubated without the drug (ANOVA, Bonferroni corrected).

Table 4 Surface expression of CD80 by dendritic cells cultured for 48 h with the indicated preparations (average fluorescence intensity in arbitrary units) Donor number No stimulation LPS The drug (units / ml) 10 one hundred 1000 one 29th 134 41 44 41 2 28 90 29th thirty thirty 3 23 124 thirty 32 33 M ± σ 27 ± 3 116 ± 23 33 ± 7 35 ± 8 * 35 ± 6 * p <0.05 when compared with expression in the absence of stimulants (ANOVA with Bonferroni correction).

Table 5 Surface expression of CD86 by dendritic cells cultured for 48 h with the indicated preparations (average fluorescence intensity in arbitrary units) Donor number No stimulation LPS The drug (units / ml) 10 one hundred 1000 one 55 145 53 56 73 2 74 134 66 68 86 3 fifty 149 48 51 78 M ± σ 60 ± 13 143 ± 8 56 ± 9 58 ± 9 79 ± 7 ** ** p <0.01 when compared with expression in the absence of stimulants (ANOVA with Bonferroni correction).

Table 7 TNF levels (pg / ml) in 24-hour MNC supernatants cultured without drugs, with LPS (positive control) and with indicated drug concentrations Donor number No stimulation LPS The drug (units / ml) 10 one hundred 1000 one 35 407 47 53 484 2 27 1011 108 154 1112 3 24 1376 17 fifteen 58 four 5 371 8 eleven 700 5 31 468 82 81 124 6 28 279 24 39 47 7 19 1300 13 eighteen 637 M ± σ 21 ± 12 816 ± 480 37 ± 39 48 ± 50 426 ± 377 *** *** p <0.001 when compared with the production of TNF in the absence of stimulants (ANOVA with Bonferroni correction)

Table 8 The amount of AOK in the spleens of experimental animals, depending on the stimulator Animal processing AOK / Splez (M ± m) AOK / 10 ° NSC village (M ± m) A drug Group number mcg / mouse Absolute Qty Modulation index Absolute Qty Modulation index Control (1% starch) one - 613 ± 120 1.00 ± 0.18 3.14 ± 0.88 1.0 ± 0.28 A drug 2 10 664 ± 103 1.08 ± 0.17 3.18 ± 0.4 1.01 ± 0.16 3 fifty 1066 ± 219 * 1.73 ± 0.36 * 5.29 ± 1.02 1.66 ± 0.33 four one hundred 344 ± 97 * 0.56 ± 0.16 1.64 ± 0.52 0.32 ± 0.10 * Interferon ** - - - - - - * p <0.05 compared with control **** Belardelli F. "Role of interferones and other cytokiness in the regulation of the immune response.//APMIS, 1995 Mar; 103 (3): 161-79); E .N. Simovyanyan, VB Denisenko, A. M. Sarychev, A. Grigoryan Chronic Epstein-Barr virus infection in children: modern aspects of diagnosis and treatment // Consilium Medicum (pediatrics) .- 2006. - N2 . - P.29-35; Ivashkin V.T. Basic concepts and provisions of fundamental immunology.Http: //www.gastro.j.run./files/s1-12_1256462343 pdf.

In general, the results obtained led to the conclusion that the proposed tool is an immunotropic drug with a complex effect that affects innate immunity cells (NK cells - natural killer cells), adaptive immunity effector cells (T cells), and also auxiliary cells adaptive immunity (DC - dendritic cells) and antibody production.

The results of the assessment of the specific properties of the new complex drug allow it to be attributed to drugs with immunomodulatory activity.

Thus, the proposed tool will significantly expand the possibilities of prevention and correction of immunological disorders in a healthy and sick person.

Claims (6)

1. A complex immunomodulating agent for the prevention of disorders and regulation of the immune system, characterized in that it is made in the form of suppositories on a hydrophilic basis and contains human recombinant interferon alpha, and / or beta, and / or gamma types, retinol palmitate and / or substances selected from among alpha, beta, gamma-carotenes, zinc sulfate monohydrate, and excipients:
basis and technological additives with the content of components, g:
Human recombinant interferon alpha, and / or beta, and / or gamma types 125 thousand-1.0 million ME Retinol palmitate and / or alpha, beta, gamma carotenes 1.1-3.3 thousand ME, Zinc sulfate monohydrate 0.005-0.015 Excipients up to 1.5 2. The complex immunomodulating agent for the prevention of disorders and regulation of the immune system according to claim 1, characterized in that polyethylene oxide 400 and polyethylene oxide 1500 are used as a base in a ratio of 1:10. 3. The complex immunomodulating agent for the prevention of disorders and regulation of the immune system according to claim 1, characterized in that ethylene diamine tetraacetic acid disodium salt and polysorbate 80 (tween 80) are used as a technological additive. 4. A comprehensive tool for the prevention of disorders and regulation of the immune system, characterized in that it is made in the form of capsules and contains human recombinant interferon alpha, and / or beta, and / or gamma types, retinol palmitate and / or other substances selected from the group of alpha, beta, gamma-carotenes, zinc sulfate monohydrate, with the content of components, g:
Human recombinant interferon alpha, and / or beta, and / or gamma types 250 thousand-1.0 million ME Retinol palmitate and / or alpha, beta, gamma carotenes 1.65-3.3 thousand ME Zinc sulfate monohydrate 0.0075-0.015 Excipients up to 0.1 5. A comprehensive tool for the prevention of disorders and regulation of the immune system according to claim 4, characterized in that corn starch is used as the basis. 6. A comprehensive tool for the prevention of disorders and regulation of the immune system according to claim 4, characterized in that hydroxypropyl cellulose, colloidal silicon dioxide, magnesium stearate are used as technological additives.