KR20160121168A - Composition for modulating immunity comprising coenzyme Q10 and omega 3 - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating immune disease, containing coenzyme Q10, omega 3, and zinc zinc as active ingredients. According to the present invention, the pharmaceutical composition for preventing or treating immune disease as a composite agent containing coenzyme Q10, omega 3, and zinc as the active ingredients can effectively suppresses production of inflammatory cytokines, and promotes differentiation induction and activation of immunoregulatory T cells, thereby being useful for producing treatment agents for immune diseases and functional health foods for preventing or ameliorating immune disease.

Description

Composition for modulating immunity comprising coenzyme Q10 and omega-3 using a combination of coenzyme Q10 and omega-

The present invention relates to a composition for preventing or treating an inflammatory immune disease using a combination of coenzyme Q10 and omega-3.

In order to protect the human body from internal and external pathogenic substances, the immune system constructs a defense system consisting of various cells, which is accomplished through the specific function of each cell and signal transmission between the cells. The immune system of the human body can be largely divided into immunity tolerance which controls immunity and immunity which promotes immunity. These two immune functions are balanced to form immunological homeostasis . However, if for some reason its balance is broken and the immune response is greater than that of immune tolerance, immune and inflammatory diseases will result.

Immunosuppression for the prevention or treatment of an immunological disease or an inflammatory disease includes a specific inhibitor and a nonspecific inhibitor that inhibit the response only. Theoretically, a specific inhibitor should be excellent, but a nonspecific inhibitor is mainly used. The most commonly used immunosuppressants are cyclosporine (Neoral, Cipol A), azathioprine (imuran), and prednisolone (a kind of steroid). Recently, there have been various immunizations such as FK 506, RATG, OKT3, Inhibitors have been developed and used.

However, these therapies have been associated with side effects such as hypertension and nephrotoxicity (decreased renal function), and the incidence of such side effects is high. Other side effects include the development of new treatments that have rare side effects such as tremors, seizures, hepatitis, retention of blood, increase in blood uric acid, decreased muscle strength, hypertrichosis, and gingival hypertrophy. It is urgent.

On the other hand, there are T cells as one of the cell groups which plays a central role in the immune system as a bio-defense system for various pathogens. T cells are produced in the thymus of the human body, and undergo a series of differentiation processes, resulting in differentiation into T cells with inherent characteristics. The differentiated T cells are largely classified into type 1 (Th1) Auxiliary cells (Th2). Among these, Th1 cells are mainly involved in cell mediated immunity, Th2 cells are involved in humoral immunity, and in the immune system, these two cell populations maintain the balance of the immune system through mutual checks to prevent mutual activation with each other.

Therefore, most of the immune diseases are caused by the imbalance between these two immune cells. For example, when the activity of Th1 cells abnormally increases, an autoimmune disease may occur and the activity of Th2 cells abnormally increases It is known that immune diseases are caused by hypersensitivity reactions.

Recent studies on the differentiation of Th1 cells have revealed the existence of a new group of immunoregulatory T cells (Tregs) capable of regulating the activity of Th1 cells, Cells have the property of suppressing the function of abnormally activated immune cells and controlling the inflammatory reaction, and many experiments for treating immune diseases through the action of increasing Treg cell activity have been reported.

In addition, Th17 cells are known to be formed through a process similar to the differentiation of Treg cells in the differentiation process of undifferentiated T cells. That is, the differentiation of Treg cells and Th17 cells is commonly performed in the presence of TGF-β, whereas IL-6 is not required for Treg cells, while IL-6 is present along with TGF-β for Th17 cells Differentiate in situations. In addition, differentiated Th17 cells are characterized by secretion of IL-17.

Th17 cells, unlike Treg cells, are involved in the forefront of the inflammatory response seen in immune diseases, thereby maximizing the signal of the inflammatory response and accelerating the progression of the disease. Therefore, in the case of autoimmune diseases that are not controlled by Treg cells among autoimmune diseases, the development of therapeutic agents for autoimmune diseases targeting the inhibition of Th17 cell activation has been greatly emphasized.

Immunosuppressants that block the signal transduction pathway in T cells are the most commonly used therapeutic agents for immune diseases. Such immunosuppressants are toxic, infectious, lymphoid, diabetes, tremor, headache, diarrhea, hypertension, nausea , And a disorder of renal function.

In addition to the method of treating immune diseases through the method of inhibiting the activation of T cells, a method of regulating the amount of cytokine secreted from the immune cells and a method of using the antibody targeting the cytokine secreted from the immune cells have been developed . However, this method has a problem in that it takes much time to actually apply to patients through clinical experiments, and that the method using antibody is too expensive in the process of antibody production.

Therefore, there is a need to develop new therapeutic agents and methods for treatment of inflammatory immune diseases which have no side effects, are cheap, and have excellent therapeutic effects.

Korea Patent Publication No. 2011-0052990

The present invention has been accomplished in order to develop a more effective therapeutic agent for immune diseases, and it has been confirmed that coenzyme Q10, omega 3 and zinc are combined with each other to provide a therapeutic effect of immune diseases.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of immune diseases comprising coenzyme Q10, omega 3 and zinc as an active ingredient.

Another object of the present invention is to provide a health functional food for preventing or ameliorating an immunological disease comprising coenzyme Q10, omega 3 and zinc as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating immune diseases comprising coenzyme Q10, omega 3 and zinc as an active ingredient.

In one embodiment of the present invention, the composition may contain coenzyme Q10: omega 3: zinc in a concentration ratio of 1: 0.05 to 4: 2 to 10, respectively.

In one embodiment of the present invention, the composition may have the effect of inhibiting the production of inflammatory cytokines and promoting activation and differentiation of immunoregulatory T cells (Tregs).

In one embodiment of the invention, the inflammatory cytokine may be IL-17, IFN-r, TNF-a and IL-6.

In one embodiment of the present invention, the immunological disease may be selected from the group consisting of autoimmune diseases, inflammatory diseases, and transplantation rejection diseases of cells, tissues or organs.

In one embodiment of the present invention, the immune disorder is selected from the group consisting of Rheumatoid Arthritis, Ankylosing Spondylitis, Asthma, Dermititis, Psoriasis, Cystic Fibrosis, Multiple sclerosis, systemic lupus erythematosus, Sjogren's syndrome, Hashimoto thyroiditis, multiple myositis, multiple sclerosis, multiple sclerosis, multiple sclerosis, inflammatory diseases such as polymyositis, scleroderma, Addison disease, vitiligo, pernicious anemia, glomerulonephritis and pulmonary fibrosis, Inflammatory Bowel Dieses, Autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, re-angiography after angioplasty, (Eg, post-angioplasty restenosis, chronic obstructive pulmonary diseases (COPD), Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease Coronary artery disease, angina, cancer metastasis, and small artery disease.

The present invention also provides a health functional food for preventing or ameliorating an immune disease comprising coenzyme Q10, omega 3 and zinc as an active ingredient.

In one embodiment of the present invention, the coenzyme Q10: omega 3: zinc may be mixed at a concentration ratio of 1: 0.05 to 4: 2 to 10, respectively.

In one embodiment of the present invention, the immunological disease may be selected from the group consisting of autoimmune diseases, inflammatory diseases, and transplantation rejection diseases of cells, tissues or organs.

In one embodiment of the present invention, the immune disorder is selected from the group consisting of Rheumatoid Arthritis, Ankylosing Spondylitis, Asthma, Dermititis, Psoriasis, Cystic Fibrosis, Multiple sclerosis, systemic lupus erythematosus, Sjogren's syndrome, Hashimoto thyroiditis, multiple myositis, multiple sclerosis, multiple sclerosis, multiple sclerosis, inflammatory diseases such as polymyositis, scleroderma, Addison disease, vitiligo, pernicious anemia, glomerulonephritis and pulmonary fibrosis, Inflammatory Bowel Dieses, Autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, re-angiography after angioplasty, (Eg, post-angioplasty restenosis, chronic obstructive pulmonary diseases (COPD), Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease Coronary artery disease, angina, cancer metastasis, and small artery disease.

Further, the present invention provides a method of differentiating undifferentiated T cells into immunoregulatory T cells (Tregs), comprising treating the undifferentiated T cells with coenzyme Q10, omega 3 and zinc in vitro.

In one embodiment of the present invention, the treatment may be to treat coenzyme Q10, omega 3 and zinc, respectively, or a combination comprising both coenzyme Q10, omega 3 and zinc.

In one embodiment of the present invention, the treatment may be to treat coenzyme Q10: omega 3: zinc at a concentration ratio of 1: 0.05 to 4: 2 to 10, respectively.

The present invention relates to a pharmaceutical composition for preventing or treating an immunological disease comprising coenzyme Q10, omega 3 and zinc as an active ingredient. The pharmaceutical composition for the prevention or treatment of immune diseases, which is a combination comprising coenzyme Q10, omega 3 and zinc as an active ingredient according to the present invention, can effectively inhibit the production of inflammatory cytokines, Inducing effect is excellent and can be usefully used for the preparation of a health functional food for the prevention or amelioration of immunological diseases and immunological diseases.

FIG. 1 shows the results of analysis of the inhibitory activity of TNF-a and IL-6, which are inflammatory cytokines by the combined treatment of coenzyme Q10, omega 3 and zinc.
FIG. 2 shows the results of analysis of the inhibitory activity of IL-17 and IFN-r, which are inflammatory cytokines by co-treatment of coenzyme Q10, omega 3 and zinc.
FIG. 3 shows the results of confirming that induction of immunoregulatory T cells (Treg) is increased when the undifferentiated T cells are treated with coenzyme Q10, omega 3 and zinc in combination.
FIG. 4 shows the results of analyzing the symptom relief effect of ankylosing spondylitis by administering coenzyme Q10, omega 3 and zinc in combination to an ankylosing spondylitis mouse model.
FIG. 5 shows the results of analyzing the relieving effect of arthritis symptoms by administering coenzyme Q10, omega 3 and zinc in combination to an arthritis-induced mouse model.
FIG. 6 shows the results of analysis of cell respiratory capacity increasing activity of coenzyme Q10, omega 3 and zinc complex treatment in synovial cells.

The present invention is characterized in that when the co-enzyme Q10, omega-3 and zinc are treated in combination to treat a new therapeutic agent for an effective immune disease, the immune disease can be effectively treated.

Accordingly, the present invention is characterized by providing a pharmaceutical composition for the prevention or treatment of immune diseases comprising coenzyme Q10, omega 3 and zinc as an active ingredient.

Among the components of the combination agent contained in the composition of the present invention, coenzyme Q10 is a compound having a isoprene unit of an ubiquinone (2,3-dimethoxy-5-methyl-6-polyprenyl-1,4-benzoquinone) Specific ubiquinone. Such coenzyme Q10 is essential for the production of adenosine triphosphate in mitochondria as coenzyme, and has been proved effective for diseases such as heart disease and hypertension. In addition, coenzyme Q10 has high physiological activity and is highly safe in vivo, so it is recommended that the coenzyme Q10 be taken up on a daily basis.

Omega-3 is an omega-3 unsaturated fatty acid, also referred to as omega-3 highly unsaturated fatty acid or polyunsaturated fatty acid (PUFA) Docosahexaenoic acid (DHA), Eicosapentaenoic acid (EPA), Docosapentaenoic acid (DPA), and? -Linolenic acid are known.

These omega-3s are known to lower cholesterol levels and lower the incidence of arteriosclerosis, and are known to affect the metabolism of our body, preventing heart disease and improving depression and dementia. These omega (ω) -3 are reported to be contained in mushrooms, tofu and pumpkin seeds.

Also, zinc, the other major component contained in the composition of the present invention, is an essential mineral present in the organism in an amount greater than any other oligoelement except iron. This is related to the general absorption of vitamins and their activities, particularly B-complex vitamins. It is a component of a large number of enzymes that play a role in the digestion and metabolism, including deacidification dehydrogenase, which is necessary for tissue respiration. Zinc is found especially in bones, teeth, skin, liver, muscle and hair in the body. It is also known that zinc is involved in the synthesis of nucleic acids that regulate the production of various proteins in cells, is also important for vitamin absorption and is useful for healing processes, as well as inhibiting bacteria, yeast and skin lysozyme lipase.

On the other hand, the deficiency of zinc causes serious obstacles, and zinc deficiency can cause growth retardation and sexual immaturity. Stretch marks and white spots on the nails are also symptoms of zinc deficiency.

 In the present invention, it is characterized in that a complex containing these three components, that is, coenzyme Q10, omega-3 and zinc as main components, is characterized by effectively treating immune diseases. According to one embodiment of the present invention, When the three components were mixed, the production of inflammatory cytokines was markedly reduced as compared with the case of treatment with a single or a mixture of two components, whereas the immunoregulatory T cells (Treg) Induction of Treg cells from undifferentiated T cells was increased.

According to another embodiment of the present invention, in order to confirm whether the compound of the present invention has an effect of practically treating immune diseases, an ankylosing spondylitis and arthritis mouse disease model is administered to coenzyme Q10, omega 3 and zinc as main components , It was confirmed that the symptom of the disease can be improved and treated most effectively when the combination of the three components is treated as compared with the group treated with these components or the group treated with the two components.

Therefore, the pharmaceutical composition for preventing or treating immune diseases comprising coenzyme Q10, omega 3 and zinc as an active ingredient according to the present invention inhibits the production of inflammatory cytokines and induces activity and differentiation of immunoregulatory T cells (Treg) TNF-a, IL-17, IFN-r, and IL-6 may be used for the inflammatory cytokine.

The coenzyme Q10: omega 3: zinc contained in the composition of the present invention is preferably contained in a concentration ratio of 1: 0.05 to 4: 2 to 10, respectively.

This was the most effective inflammatory cytokine inhibitory effect when coenzyme and omega zinc were mixed at the concentration ratios described above, and this concentration was very effective in activating and promoting differentiation of immunoregulatory T cells. On the other hand, when the concentration is outside the above range, the effect of inhibiting the production of inflammatory cytokines is insufficient. Also, when zinc is used in an excessive amount compared with the above-mentioned concentration, The use of a small amount of T cells causes a problem that the activity and induction of differentiation of T cells are lowered.

In addition, the immunological diseases treatable by the complex of the present invention may include autoimmune diseases, inflammatory diseases, and transplantation rejection diseases of cells, tissues or organs, and the immune diseases include, but are not limited to, Rheumatoid arthritis, Ankylosing spondylitis, Asthma, Dermititis, Psoriasis, Cystic Fibrosis, Post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosus, Sjogren's syndrome, Hashimoto thyroiditis, polymyositis, scleroderma, Adison's disease Addison disease, vitiligo, pernicious anemia, glomerulonephritis and pulmonary fibrosis, inflammatory Inflammatory bowel disease, inflammatory bowel dieses, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, Chronic obstructive pulmonary diseases (COPD), Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina pectoris Angina), cancer metastasis, and small artery disease.

In addition, inflammatory diseases include TNF-α, IL-1 (interleukin-1), IL-1 (interleukin-1 and IL-2) secreted from immune cells such as macrophages by overexpression of the human immune system due to harmful stimuli, Inflammatory substances such as inflammatory cytokines such as IL-1, IL-6, prostagladin, luecotriene or nitric oxide (NO).

The term treatment refers to reversing, alleviating, inhibiting, or preventing the disease or disorder to which the term applies, or one or more symptoms of the disease or disorder, unless otherwise stated, As used herein, the term " treatment " refers to an act of treating when the treatment is defined as above. The therapeutic or therapeutic treatment of an immune disorder in a mammal therefore may include one or more of the following:

(1) inhibiting the growth of the immune system, i.e., inhibiting its development,

(2) preventing the spread of immune diseases, i.e., preventing metastasis,

(3) Reducing immune diseases.

(4) preventing the recurrence of immune disorders, and

(5) palliating symptoms of immune disorders

A composition for the prevention or treatment of an immune disorder according to the present invention comprises a pharmaceutically effective amount of coenzyme Q10, omega 3 and zinc, and may further comprise at least one pharmaceutically acceptable carrier, excipient or diluent. A pharmaceutically effective amount as used herein refers to an amount sufficient to prevent, ameliorate, and treat symptoms of an immune disease.

The combination of coenzyme Q10, omega-3 and zinc according to the present invention may be used at 0.1 to 100 mg / day / kg body weight, preferably 0.5 to 5 mg / day / kg body weight. However, the pharmacologically effective amount may be appropriately changed depending on the severity of the immune disease symptoms, the age, body weight, health condition, sex, administration route and treatment period of the patient.

The term " pharmaceutically acceptable " as used herein refers to a composition that is physiologically acceptable and does not normally cause an allergic reaction such as gastrointestinal disorder, dizziness, or the like when administered to humans. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. Further, it may further include a filler, an anticoagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent and an antiseptic agent.

In addition, the compositions of the present invention may be formulated using methods known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to the mammal. The formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatine capsules, sterile injectable solutions, sterile powders.

In addition, the composition for preventing or treating immunological diseases according to the present invention may be administered through various routes including oral, transdermal, subcutaneous, intravenous, or muscular, and the dose of the active ingredient may be appropriately determined depending on the route of administration, The composition of the present invention can be appropriately selected according to various factors such as body weight and the severity of the patient and the composition for preventing or treating immune diseases according to the present invention can be used in combination with known compounds having the effect of preventing, Lt; / RTI >

The present invention also provides a health functional food composition for preventing or ameliorating an immunological disease comprising coenzyme Q10, omega 3 and zinc as an active ingredient.

The food composition according to the present invention may contain coenzyme Q10, omega-3 and zinc, which are effective ingredients, as well as various flavoring agents or natural carbohydrates as additional components such as ordinary food compositions.

Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. The above-described flavors can be advantageously used as natural flavorings (tau martin), stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.).

The food composition of the present invention can be formulated in the same manner as the above pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolates, foods, confectionery, pizza, ram noodles, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes, .

In addition, the food composition may contain flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.) such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors in addition to the active ingredients Coenzyme Q10, Omega 3, Organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the food composition of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks.

The health functional food of the present invention can be manufactured and processed in the form of tablet, capsule, powder, granule, liquid, ring and the like for the purpose of prevention, improvement and treatment of immune diseases.

In the present invention, the term " health functional food " refers to foods manufactured and processed using raw materials or ingredients having useful functions in accordance with Law No. 6727 on Health Functional Foods. Or to obtain a beneficial effect in health use such as physiological action.

The health functional foods of the present invention may contain conventional food additives and, unless otherwise specified, whether or not they are suitable as food additives are classified according to the General Rules for Food Additives approved by the Food and Drug Administration, Standards and standards.

Examples of the items listed in the above-mentioned "food additives" include chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as persimmon extract, licorice extract, crystalline cellulose, high color pigment and guar gum; L-glutamic acid sodium preparations, noodle-added alkalis, preservative preparations, tar coloring preparations and the like.

For example, the health functional food in the form of tablets may be prepared by granulating a mixture obtained by mixing the active ingredient of the present invention with an excipient, a binder, a disintegrant and other additives, granulating the mixture in a conventional manner, The mixture can be directly compression molded. In addition, the health functional food of the tablet form may contain a mating agent or the like if necessary.

The hard capsule of the capsule type health functional food may be prepared by filling a normal hard capsule with a mixture of the active ingredient of the present invention and an additive such as an excipient. The soft capsule may contain the active ingredient of the present invention as an excipient And filling the mixture with a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.

The ring-shaped health functional food can be prepared by molding a mixture of coenzyme Q10, omega 3 and zinc, which are the effective components of the present invention, together with an excipient, a binder, a disintegrant, and the like by a conventionally known method, Or other skin care agent, or the surface may be coated with a material such as starch or talc.

The granular health functional food can be prepared by granulating a mixture of coenzyme Q10, omega 3 and zinc, which are the active ingredients of the present invention, with excipients, binders, disintegrators, and the like by a conventionally known method, Flavoring agents, mating agents, and the like.

The health functional food may be a beverage, a meat, a chocolate, a food, a confectionery, a pizza, a ramen, a noodle, a gum, a candy, an ice cream, an alcoholic beverage, a vitamin complex and a health supplement food.

Further, the present invention provides a method for differentiating or activating undifferentiated T cells into immunoregulatory T cells (Tregs), comprising treating the undifferentiated T cells with coenzyme Q10, omega 3 and zinc in vitro.

In the above method, the method of treating cells with an effective ingredient of the present invention may be a method of directly treating all the active ingredients in the culture medium for culturing the cells or treating a complex containing three active ingredients.

It is also preferable that the above treatment is carried out at a concentration ratio of coenzyme Q10: omega 3: zinc of 1: 0.05 to 4: 2 to 10, respectively.

In the present invention, the above-mentioned activity means that all mechanisms of Treg cells including regulatory T cells (T reg), that is, natural Treg and adaptive Treg cells, are promoted or promoted in vivo Refers to promoting or enhancing an immunomodulatory action such as an immunosuppressive reaction so that the immune response in vivo maintains a normal state.

In addition, the 'differentiation' refers to a phenomenon in which a structure or function is specialized with each other while a cell is growing and proliferating, that is, a form or a function is changed in order to carry out a task given to each cell, 'Proliferation' refers to the division of cells into homogeneous, usually increasing the number of cells in the body of multicellular organisms.

In addition, the technical feature to be provided through the present invention is that a therapeutic agent for the concept of a complex agent using Coenzyme Q10, Omega 3 and Zinc is very effective as a new immunomodulating therapeutic agent which is more effective than the prior art.

In particular, in the present invention, omega 3 was used to enhance intracellular uptake of coenzyme Q10, and it was confirmed that coenzyme Q10 can increase the intracellular uptake of coenzyme Q10 as compared with coenzyme Q10 alone treatment. Zinc inhibits the inflammatory activity of immune cells And coenzyme Q10 and omega-3 were used to more effectively inhibit the pathological inflammation of immune cells and to protect the immune regulatory cells of anti-inflammation.

Therefore, the combination agent for the treatment of immune diseases provided by the present invention can restore mitochondrial function and regenerate damaged cells, regulate cell metabolism, prevent mitochondrial activity by coenzyme Q10, metabolic function by omega 3, and prevention of metabolic syndrome treatment It is possible to maximize the improvement of immunity by controlling the complex mechanism of the immune modulating effect through the use of zinc.

Hereinafter, the present invention will be described in detail by way of the following examples, but the present invention is not limited thereto for any reason.

< Example  1>

Coenzyme Q10 , Omega 3 and Zinc in Combination Treatment of Inflammatory Cytokines

<1-1> TNF -a and IL -6 inhibitory activity assay

The present inventors prepared a combination of coenzyme Q10, omega 3 and zinc as a new combination agent capable of effectively controlling the inflammation. OeGa 3 was dissolved in chloroform and dissolved in a solvent of EPA: methanol, DHA: DMSO Zinc was dissolved in water and used. That is, a combination of Coenzyme Q10, Omega 3 and Zinc was prepared by mixing these components dissolved in each solvent at a concentration ratio of 0.1 mg / ml, Omega 3 0.2 mg / ml and Zinc 0.02 mg / ml .

The thus prepared complex of the present invention was treated with CD4 + T cells isolated from C57BL / 6 normal mice stimulated with LPS, which is an inflammation inducer, and cultured for 48 hours. Then, the culture solution was collected to collect TNF -a and IL-6 were confirmed by ELISA.

Specifically, for ELISA analysis, anti-TNF-a and anti-IL-6 were incubated in 96 well plate at 2 ug / ml, respectively, and then incubated overnight at 4 ° C. (1% BSA / PBST), and then TNF-a and IL-6 recombinants were serially diluted by ½ successive times. The cells were incubated for 2 hours at room temperature with the cell culture supernatant . Biotinylated anti-TNF-a and anti-IL-6 were incubated for 2 hours at room temperature for 2 hours, washed 4 times, added with ExtraAvidin-Alkaline Phosphatase conjugate and reacted at room temperature for 2 hours. After that, PNPP / DEA solution was added to develop color, and absorbance was measured at 405 nm wavelength after color development. At this time, LPS-stimulated cells were treated with LPS alone, LPS-stimulated cells were treated with coenzyme Q10 alone, and coenzyme Q10 and omega-3 cells were used as controls.

As a result of the analysis, as shown in Fig. 1, the coenzyme Q10 and omega 3-treated groups showed a suppression of inflammatory cytokine production compared with the coenzyme Q10-treated group, and compared with coenzyme Q10 and omega 3 treated groups The combination of coenzyme Q10, omega 3 and zinc showed the highest inhibition of the production and activity of TNF-a and IL-6.

<1-2> Th17 and Th1  Inhibitory activity assay

The same experiment was performed except that monoclonal anti-IL-17 and anti-IFN-r were used for ELISA analysis in the experiment of Example <1-1> above.

As a result, as shown in Fig. 2, the coenzyme Q10 and omega-3 treatment groups inhibited the production of inflammatory cytokines, compared to coenzyme Q10 alone treatment group, and compared with coenzyme Q10 and omega 3 treatment groups The combination of coenzyme Q10, omega 3 and zinc showed the most inhibition of the production and activity of IL-17 and interferon gamma.

< Example  2>

Coenzyme Q10 , Omega-3 and zinc Treg  Active promoting effect

The present inventors conducted the following experiment to confirm whether the combination of coenzyme Q10, omega 3 and zinc promotes the activity of Treg cells having immunomodulatory ability.

First, the spleen cells obtained from the mice were treated with 0.5 ug / ml of anti-CD3 and 100 ng / ml of LPS. After the complex of the present invention was treated for 48 hours, FACS staining was performed. FACS staining was performed 4 hours after Golgi stop treatment.

After culturing the cells, the cells were washed with FACS buffer (PBS, 0.5-1% BSA, 0.1% sodium azide) and treated with Anti-CD4 Percp-Cy5.5 and Anti-CD25 APC Ab for 25 minutes (BD Bioscience, Cat. 554715), and reacted at 4 ° C for 30 minutes after treatment with Cytofix / Cytoperm buffer (BD Bioscience, Cat. 554715). Then, the cells were reacted with anti-IL-17 FITC and anti-Foxp3 PE at 4 ° C, analyzed by FACS Calibur, and analyzed using Flow Jo. A (Tree Star, Vx Version).

 As a result, as shown in FIG. 3, in the group treated with the combination of coenzyme Q10, omega 3 and zinc, the induction to Treg cells was increased compared to the group treated with coenzyme Q10 alone, The expression of Foxp3, a marker of T cell, and the number of Foxp3 expressing cells were increased.

< Example  3>

Coenzyme Q10 , Omega 3 and Zinc in Combination Treatment of Ankylosing Spondylitis

The following tests were conducted on an animal model inducing anchoring hypercholesterolemia in order to confirm that the complex of the combination according to the present invention, coenzyme Q10, omega 3 and zinc can improve the symptoms of ankylosing spondylitis and treat the disease.

First, Curdlan (Wako, 034-09901) powder was dissolved in saline for SKG (Osaka University, Shimon Sakaguchi) mouse, and injected intravenously at a dose of 3 mg / mouse to induce ankylosing spondylitis to induce an ankylosing spinal cord preeclampsia model .

One week after injection of curdaln, oral administration of coenzyme Q10 0.1 mg / mouse, omega-3 0.2 mg / mouse and zinc 0.02 mg / mouse was administered orally to the ankylosing spondylitis mouse model, And coenzyme Q10 alone.

Analysis of symptom improvement of ankylosing spondylitis was analyzed according to the following criteria.

 0 point: no swell and no redness

 0.1 point: swelling of the toes and redness,

0.5 points: The degree of symptom improvement was evaluated by scoring wrists and ankles with swelling and redness.

As a result, as shown in Fig. 4, the symptoms of ankylosing spondylitis were significantly improved in the group treated with three components compared with the group treated only with coenzyme Q10, Compared with about 2 times more than the therapeutic effect was.

< Example  4>

Coenzyme Q10 , Omega 3 and Zinc Combination Treatment

Zymosan (Sigma aldrich, Z4250) was intravenously injected into SKG mouse (Osaka University, Shimon Sakaguchi) in an amount of 2 mg / mouse to prepare a mouse model in which autoimmune arthritis was induced. After one week, mice were orally administered a combination preparation containing coenzyme Q10 0.1 mg / ml, omega 3 0.2 mg / ml, zinc (Zinc) 0.02 mg / ml, and then arthritis index was analyzed.

As a result of the analysis, as shown in Fig. 5, the arthritic index of the group treated with the combination preparation containing three components was significantly lower than that of the group treated only with coenzyme Q10, . These results were also superior to those of the combination of coenzyme Q10 and omega-3.

< Example  5>

Coenzyme Q10 , Omega 3 and zinc complex treatment

RA synovial cells were cultured on a 24-well plate for respiratory measurement, and starvation was carried out for 24 hours. On the day of measurement, Oilgomycin and an inflammatory inducer IL-17), Injection 2 was treated with FCCP + toxic drug or FCCP + CoQ10 + Omega3, and Antimycin A + Rotenone was added to plate drug port in Injection 3, and then XF Analyzers (Seahorse) software Respiratory ability was measured for 3 hours

RA synovial cells were cultured on a 24-well plate (24 well) for CO 2 uptake by coenzyme Q10 and omega-3. After starvation for 24 hours, the plate was incubated for 1 hour in a CO2-free incubator Respectively. Injection 1 was used as an inhibitor of ATP synthesis, and Oilgomycin A (sigma, 75351) and inflammation inducer (IL-17) were used for Injection 1, and mitochondrial uncoupler (Sigma, C2920) + toxicity drug or FCCP, coenzyme Q10 and omega 3, which inhibit oxidative phosphorylation, and antimycin A (sigma, A8674) + rotenone (sigma, R8875) (Seahorse) software for 3 hours.

As a result of these experiments, the respiration ability of the mitochondria inhibited by the toxic drug was found to be recovered again in the combined treatment group than in the cochineal monotherapy. Therefore, it was found that the combination agent provided by the present invention can restore the function of mitochondria (see FIG. 6).

The present invention has been described above with reference to preferred embodiments. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

Claims (13)

Coenzyme Q10, omega-3 and zinc as an active ingredient. The method according to claim 1,
Wherein the composition contains coenzyme Q10: omega 3: zinc in a concentration ratio of 1: 0.05 to 4: 2 to 10, respectively. The method according to claim 1,
Wherein said composition has the effect of inhibiting the production of inflammatory cytokines and promoting the activation and induction of differentiation of immunoregulatory T cells (Tregs). The method of claim 3,
Wherein said inflammatory cytokine is IL-17, IFN-r, TNF-a and IL-6. The method according to claim 1,
Wherein said immune disease is selected from the group consisting of autoimmune diseases, inflammatory diseases and transplantation rejection diseases of cells, tissues or organs. 6. The method of claim 5,
The immunological diseases are selected from the group consisting of Rheumatoid Arthritis, Ankylosing spondylitis, Asthma, Dermititis, Psoriasis, Cystic Fibrosis, Post Organ Transplantation and Chronic Rejection multiple sclerosis, systemic lupus erythematosus, Sjogren's syndrome, Hashimoto thyroiditis, polymyositis, scleroderma, scleroderma, And is useful for the treatment and prevention of diabetes mellitus such as Addison disease, vitiligo, pernicious anemia, glomerulonephritis and pulmonary fibrosis, inflammatory bowel dieses, autoimmune diabetes, Retinopathy, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, Chronic obstructive pulmonary diseases (COPD), Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina ), Cancer metastasis, and small artery disease. Coenzyme Q10, omega-3 and zinc as active ingredients for the prevention or improvement of immunological diseases health functional food. 8. The method of claim 7,
Wherein the coenzyme Q10: omega 3: zinc is mixed at a concentration ratio of 1: 0.05 to 4: 2 to 10, respectively. 8. The method of claim 7,
Wherein said immune disease is selected from the group consisting of autoimmune diseases, inflammatory diseases and transplantation rejection diseases of cells, tissues or organs. 10. The method of claim 9,
The immunological diseases are selected from the group consisting of Rheumatoid Arthritis, Ankylosing spondylitis, Asthma, Dermititis, Psoriasis, Cystic Fibrosis, Post Organ Transplantation and Chronic Rejection multiple sclerosis, systemic lupus erythematosus, Sjogren's syndrome, Hashimoto thyroiditis, polymyositis, scleroderma, scleroderma, And is useful for the treatment and prevention of diabetes mellitus such as Addison disease, vitiligo, pernicious anemia, glomerulonephritis and pulmonary fibrosis, inflammatory bowel dieses, autoimmune diabetes, Retinopathy, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, Chronic obstructive pulmonary diseases (COPD), Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina ), Cancer metastasis, and small artery disease. A method of differentiating undifferentiated T cells into immunoregulatory T cells (Tregs), comprising treating the undifferentiated T cells with coenzyme Q10, omega 3 and zinc in vitro. 12. The method of claim 11,
Characterized in that the treatment comprises treating coenzyme Q10, omega 3 and zinc, respectively, or with a combination of both coenzyme Q10, omega 3 and zinc. 12. The method of claim 11,
Wherein the treatment is carried out at a concentration ratio of coenzyme Q10: omega 3: zinc of 1: 0.05 to 4: 2 to 10, respectively.

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