KR102508622B1 - Composition for preventing or treating immune diseases comprising mixture of microbiome - Google Patents

Abstract

The present invention relates to a composition for preventing and treating immune diseases comprising a microbiome mixture, and is effective in preventing and treating related immune diseases by relieving arthritis pain, protecting cartilage, and suppressing inflammatory markers.

Description

Composition for preventing and treating immune diseases containing a microbiome mixture

The present invention provides a composition for preventing and treating immune diseases comprising a microbiome mixture.

Immune diseases are diseases in which components of the mammalian immune system cause, mediate, or otherwise contribute to pathologies in mammals, and inflammatory disorders in particular are among the most important health problems worldwide. Inflammation is a localized protective response of body tissues against host invasion, generally by foreign substances or harmful stimuli. Causes of inflammation include infectious causes such as bacteria, viruses and parasites; physical causes such as burns or irradiation; chemicals such as toxins, drugs or industrial agents; It may be an immune response, such as allergic and autoimmune reactions, or conditions associated with oxidative stress.

Inflammation is characterized by pain, redness, swelling, heat, and eventual loss of function of the affected area. These symptoms are the result of a complex series of interactions between the cells of the immune system. The cellular response results in the creation of an interactive network of several groups of inflammatory mediators: proteins (e.g. cytokines, enzymes (e.g. proteases, peroxidases), major basic proteins, adhesion molecules ( ICAM, VCAM), lipid mediators (e.g. eicosanoids, prostaglandins, leukotrienes, platelet activating factor (PAF)), reactive oxygen species (e.g. hydroperoxides, superoxide anion O2-, nitric oxide (NO), etc.) However, most of these mediators of inflammation are also regulators of normal cellular activity, so the lack of an inflammatory response results in uncontrolled damage to the host (i.e., infection) and, therefore, partial partial As such, inflammatory diseases mediated by excessive production of several of the above-mentioned mediators are caused In addition, autoimmune diseases, one of immune diseases, are characterized in that the immune system attacks its own organs to cause spontaneous reactions. These responses are due to the recognition of auto-antigens by T lymphocytes, resulting in humoral (autoantigen production) and cellular (increased lymphocyte and macrophage cytotoxic activity) immune responses.

The microbiome refers to the microorganisms that live in the human body and includes the microorganisms in the gut. The number of microbiome is more than twice the number of pure human cells, and the number of genes is more than 100 times. Therefore, it is also called the Second Genome because it is impossible to discuss human genes without mentioning microorganisms. The microbiome is a field that can be widely used in the development of new drugs and research on treatments for incurable diseases, as it can analyze the principles by which beneficial and harmful bacteria are created and the relationship between diseases. The microbiome is also used in the development of food, cosmetics, and therapeutics. However, since most of the drug development research using this technology is in its infancy, it is expected that it will take time to develop products.

Korean Patent Registration No. 10-1723265

In order to solve the above problems, the present inventors have used a microbiome mixture composition in which strains of the genus Lactobacillus among probiotics are mixed as an active ingredient, thereby reducing arthritis pain, protecting cartilage, and suppressing inflammatory markers. The present invention was completed by confirming that it is effective in preventing and treating related immune diseases.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating immune diseases, comprising a mixture of strains of the genus Lactobacillus as an active ingredient, and a method for treating immune diseases using the same.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating immune diseases, comprising a mixture of strains of the genus Lactobacillus as an active ingredient.

In addition, the present invention provides a health functional food composition for preventing or improving immune diseases, comprising a mixture of strains of the genus Lactobacillus as an active ingredient.

In addition, the present invention provides a method for preventing or treating immune diseases, comprising administering the pharmaceutical composition for preventing or treating immune diseases according to the present invention to a subject in need of treatment.

The composition of the present invention is a mixture of strains of the genus Lactobacillus, which is a microbiome, and can relieve pain of arthritis and reduce joint damage. In addition, the composition of the present invention inhibits inflammatory markers and can be usefully used for preventing and treating immune diseases.

1 is a result of confirming the pain evaluation (Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL)) according to the treatment of the microbiome mixture composition of the present invention to an arthritic animal model.
2 is a result confirming the osteoarthritis pain control effect according to the treatment of the microbiome mixed composition of the present invention in an arthritic animal model.
3 is a CT analysis result confirming the ability to inhibit cartilage damage according to the treatment of the microbiome mixture composition of the present invention.
Figure 4 shows the results of measuring CTX-II in plasma according to the treatment of the microbiome mixture composition of the present invention.
Figure 5 shows the immune modulatory effect according to the treatment of the microbiome mixture composition of the present invention.
Figure 6 shows the immune modulatory effect according to the treatment of the microbiome mixture composition of the present invention.

Hereinafter, the present invention will be described in detail with embodiments of the present invention. However, the following embodiments are presented as examples of the present invention, and the present invention is not limited thereby, and various modifications and applications of the present invention are possible within the description of the claims described later and equivalent scope interpreted therefrom. .

The present invention provides a pharmaceutical composition for preventing or treating immune diseases, comprising a strain mixture of the genus Lactobacillus as an active ingredient.

The strains of the genus Lactobacillus are Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum plantarum), Lactobacillus Helveticus, Lactobacillus fermentum, Lactobacillus paracasei, and Lactobacillus salivarius. , For example, it may be a complex mixture of three strains of Lactobacillus reuteri, Lactobacillus rhamnosus and Lactobacillus acidophilus, but is not limited thereto. The three strains of Lactobacillus reuteri, Lactobacillus rhamnosus and Lactobacillus acidophilus can be mixed at a ratio of 1: 1: 1 to 1: 1: 2 However, it is not limited thereto.

The strain may be cultured and used, and may be used in the form of a fermentation broth obtained by culturing in a culture medium, a concentrated fermentation broth, a dried fermentation broth, a culture filtrate, a concentrated culture filtrate, or a dried culture filtrate. It may be a culture filtrate from which strains are removed after culturing or containing. In addition, the formulation of the culture is not limited, and may be, for example, liquid or solid.

In the present invention, the term "cultivation" means to grow microorganisms under appropriately artificially controlled environmental conditions.

The strain can grow in a normal medium, and in order to culture a specific microorganism, it contains nutrients required by the microorganism to be cultured, that is, a substance for a special purpose may be additionally added and mixed. The medium is also referred to as an incubator or a culture medium, and is a concept that includes all of a natural medium, a synthetic medium, or a selective medium.

The medium used for culture must meet the requirements of a specific strain in an appropriate manner while controlling temperature, pH, etc. in a normal medium containing an appropriate carbon source, nitrogen source, amino acid, vitamin, etc. As a carbon source that can be used, a mixed sugar of glucose and xylose is used as the main carbon source, and in addition to sugars and carbohydrates such as sucrose, lactose, fructose, maltose, starch, and cellulose, soybean oil, sunflower oil, castor oil, and coconut Oils and fats such as oil, fatty acids such as palmitic acid, stearic acid and linoleic acid, alcohols such as glycerol and ethanol, and organic acids such as acetic acid. These materials may be used individually or as a mixture. Nitrogen sources that can be used include inorganic nitrogen sources such as ammonia, ammonium sulfate, ammonium chloride, ammonium acetate, ammonium phosphate, ammonium carbonate, and ammonium nitrate; Amino acids such as glutamic acid, methionine, and glutamine, and organic nitrogen sources such as peptone, NZ-amine, meat extract, yeast extract, malt extract, corn steep liquor, casein hydrolysate, fish or decomposition products thereof, defatted soybean cake or decomposition products thereof, may be used. can These nitrogen sources may be used alone or in combination. The medium may contain monopotassium phosphate, dipotassium phosphate and corresponding sodium-containing salts as phosphorus.

Persons that may be used include potassium dihydrogen phosphate or dipotassium hydrogen phosphate or the corresponding sodium-containing salts. In addition, as the inorganic compound, sodium chloride, calcium chloride, iron chloride, magnesium sulfate, iron sulfate, manganese sulfate, and calcium carbonate may be used. Finally, essential growth substances such as amino acids and vitamins may be used in addition to the above substances. In addition, precursors suitable for the culture medium may be used. The above raw materials may be added in a batch, fed-batch or continuous manner by a method suitable for the culture during the culture process, but is not particularly limited thereto. Basic compounds such as sodium hydroxide, potassium hydroxide, ammonia or acid compounds such as phosphoric acid or sulfuric acid can be used in an appropriate manner to adjust the pH of the culture.

The immune disease increases the expression level of CTX-II; IL-17 and Th17 cells are increased; It may be a disease with a condition in which IL-10 is reduced, including, for example, an autoimmune disease or an inflammatory disease.

In the present invention, the term "autoimmune disease" refers to the unresponsiveness of the body to self-antigens as immunologic unresponsiveness or tolerance, and when problems arise in inducing or maintaining such self-tolerance An immune response against self-antigens occurs, and as a result, a phenomenon of attacking one's own tissue occurs, which means a disease caused by this process.

In the present invention, the term "inflammatory disease" is TNF-α (tumor necrosis factor-α), IL secreted from immune cells such as macrophages by excessively enhancing the human immune system due to harmful stimuli such as inflammation-inducing factors or irradiation It refers to a disease caused by proinflammatory substances (inflammatory cytokines) such as -1 (interleukin-1), IL-6, prostaglandin, luecotriene or nitric oxide (NO). .

The immune diseases include osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, spondyloarthropathy, inflammatory bowel disease, psoriatic arthritis, gout, bacterial arthritis, juvenile rheumatoid arthritis, lupus, scleroderma, multiple sclerosis, fibromyalgia, polymyositis, dermatomyositis, Behcet's disease, Reiter syndrome, Lyme arthritis, adhesive capsulitis, frozen shoulder, tendon synovitis, elbow capitis, Dquabane tendon synovitis, recurrent rheumatism, polymyalgia rheumatica, adult form Still's disease, autoimmune cytopenia, autoimmune myocarditis, atopic dermatitis , asthma, primary cirrhosis, Goodpeicher syndrome, autoimmune meningitis, Sjogren's syndrome, Addison's disease, alopecia areata, autoimmune hepatitis, autoimmune mumps, Crohn's disease, insulin-dependent diabetes mellitus, dystrophic epidermolysis bullosa, epididymitis, glomeruli Nephritis, Graves' disease, Guillain-Barre syndrome, Hashimoto's disease, hemolytic anemia, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, psoriasis, rheumatoid fever, sarcoidosis, scleroderma, spondyloarthrosis, thyroiditis, vasculitis, vitiligo, myxedema, pernicious anemia, mitochondria At least one selected from the group consisting of related syndromes and ulcerative colitis, but is not limited thereto.

In the present invention, "treatment", unless otherwise stated, is to reverse, alleviate, inhibit the progression of, or prevent the disease or disorder to which the term applies, or one or more symptoms of the disease or disorder. The term treatment, as used herein, refers to the act of treating when "treating" is defined as above. Accordingly, “treatment” or “therapy” of an immune disorder in a mammal may include one or more of the following:

(1) inhibits the growth of immune diseases, i.e., arrests their development;

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

(3) Alleviate immune diseases.

(4) preventing the recurrence of immune diseases, and

(5) palliating the symptoms of immune disorders.

The pharmaceutical composition of the present invention may further include an adjuvant in addition to the active ingredient. As long as the adjuvant is known in the art, any one may be used without limitation, but, for example, Freund's complete adjuvant or incomplete adjuvant may be further included to increase immunity.

The pharmaceutical composition according to the present invention may be prepared in the form of incorporating the active ingredient into a pharmaceutically acceptable carrier. Here, the pharmaceutically acceptable carrier includes carriers, excipients and diluents commonly used in the pharmaceutical field. Pharmaceutically acceptable carriers usable in the pharmaceutical composition of the present invention include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The pharmaceutical composition of the present invention may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories or sterile injection solutions according to conventional methods, respectively. .

When formulated, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, and gelatin in addition to active ingredients. It can be prepared by mixing etc. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid formulations for oral administration include suspensions, solutions for oral administration, emulsions, syrups, etc. In addition to commonly used diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. can Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for suppositories, witepsol, tween 61, cacao paper, laurin paper, glycerogelatin, and the like may be used.

The pharmaceutical composition according to the present invention can be administered to a subject by various routes. All modes of administration are contemplated, eg oral, intravenous, intramuscular, subcutaneous, intraperitoneal injection.

The dosage of the pharmaceutical composition according to the present invention is selected in consideration of the age, weight, sex, and physical condition of the subject. It is obvious that the concentration of the active ingredient included in the pharmaceutical composition can be variously selected according to the subject, and is preferably included in the pharmaceutical composition at a concentration of 0.01 to 5,000 μg/ml. If the concentration is less than 0.01 μg/ml, pharmacological activity may not appear, and if the concentration exceeds 5,000 μg/ml, toxicity to the human body may be exhibited.

The pharmaceutical composition may be formulated into various oral or parenteral dosage forms.

Formulations for oral administration include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, granules, etc. chlorose, mannitol, sorbitol, cellulose and/or glycine), lubricants such as silica, talc, stearic acid and magnesium or calcium salts thereof and/or polyethylene glycol. In addition, the tablet may contain a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases starch, agar, alginic acid or a disintegrant or effervescent mixture, such as its sodium salt, and/or absorbents, colorants, flavors, and sweeteners. The formulation may be prepared by conventional mixing, granulating or coating methods.

In addition, a typical formulation for parenteral administration is an injection formulation, and water, Ringer's solution, isotonic physiological saline or suspension may be used as a solvent for the injection formulation. Sterile fixed oils of the above injectable formulations may be used as a solvent or suspending medium, and any bland fixed oil may be employed for this purpose, including mono-, di-glycerides.

In addition, the formulation for injection may use a fatty acid such as oleic acid.

In addition, the present invention provides a health functional food composition for preventing or improving immune diseases, comprising a mixture of strains of the genus Lactobacillus as an active ingredient.

In addition to containing the active ingredient, the food composition of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients like conventional food compositions.

Examples of the aforementioned natural carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins and cyclodextrins, and sugar alcohols such as xylitol, sorbitol and erythritol. As the flavoring agents described above, natural flavoring agents (thaumatin), stevia extracts (eg rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can advantageously be used. The food composition of the present invention can be formulated in the same way as the 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, chocolate, foods, confectionery, pizza, ramen, other noodles, gum, candy, ice cream, alcoholic beverages, vitamin complexes and health supplements, etc. there is

In addition, the food composition, in addition to the active ingredient extract, various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, Alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like may be contained. In addition, the food composition of the present invention may contain fruit flesh for preparing natural fruit juice, fruit juice beverages, and vegetable beverages.

The functional food composition of the present invention can be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills, and the like. In the present invention, 'health functional food composition' refers to a food manufactured and processed using raw materials or ingredients having useful functionality for the human body according to Health Functional Food Act No. 6727, and the structure and function of the human body It refers to intake for the purpose of obtaining useful effects for health purposes such as regulating nutrients or physiological functions. The health functional food of the present invention may contain ordinary food additives, and the suitability as a food additive is determined according to the general rules of the Food Additive Code and General Test Methods approved by the Food and Drug Administration, unless otherwise specified. It is judged according to standards and standards. Examples of the items listed in the 'Food Additive Code' include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, kaoliang pigment, and guar gum; and mixed preparations such as sodium L-glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar color preparations. For example, a health functional food in the form of a tablet is obtained by granulating a mixture obtained by mixing the active ingredient of the present invention with an excipient, a binder, a disintegrant, and other additives in a conventional manner, and then adding a lubricant or the like to compression molding, or as described above. The mixture can be directly compression molded. In addition, the health functional food in the form of a tablet may contain a flavoring agent and the like as needed. Among health functional foods in the form of capsules, hard capsules can be prepared by filling a mixture in which the active ingredient of the present invention is mixed with additives such as excipients in a normal hard capsule. It can be prepared by filling the mixture mixed with gelatin in a capsule base. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary. The health functional food in the form of a pill can be prepared by molding a mixture of the active ingredient of the present invention mixed with an excipient, a binder, a disintegrant, etc. by a conventionally known method, and can be coated with sucrose or other coating agent if necessary, Alternatively, the surface may be coated with a material such as starch or talc. Health functional food in the form of granules can be prepared in granular form by a conventionally known method of mixing the active ingredient of the present invention with excipients, binders, disintegrants, etc., and, if necessary, flavoring agents, flavoring agents, etc. can

In addition, the present invention provides a method for preventing or treating an immune disease comprising administering a pharmaceutical composition for preventing or treating an immune disease to a subject in need of treatment.

The treatment method of the present invention comprises administering to a subject a therapeutically effective amount of the pharmaceutical composition. A specific therapeutically effective amount for a specific individual depends on the type and degree of response to be achieved, the specific composition, including whether other agents are used as the case may be, the age, weight, general health condition, sex and diet of the individual, the time of administration, It is preferable to apply differently according to various factors including the route of administration and secretion rate of the composition, treatment period, drugs used together with or concurrently used with the specific composition, and similar factors well known in the medical field. Therefore, the effective amount of the composition suitable for the purpose of the present invention is preferably determined in consideration of the above.

The subject is applicable to any mammal, and the mammal includes humans and primates as well as livestock such as cattle, pigs, sheep, horses, dogs, and cats.

The present invention will be described in more detail through the following examples. However, the following examples are only for specifying the content of the present invention, and the present invention is not limited thereto.

[Example]

Example 1. Preparation of the microbiome mixture composition of the present invention

Lactobacillus reuteri, Lactobacillus rhamnosus, and Lactobacillus acidophilus are mixed at a ratio of 1:1:1 to 1:1:2 to obtain microbiome. An ohmic mixture composition was prepared.

Example 2. The therapeutic effect of the microbiome mixture composition of the present invention on osteoarthritis

Monosodium Iodoacetate (MIA, I2512, Sigma, Poole, UK) was dissolved in saline for injection at a concentration of 60 mg/ml and prepared on the day of the experiment (day 0). On the first day of the experiment, the rat (Wistar rat, 6 weeks old, 180 g ~ 220 g) was anesthetized with isoflurane, and then MIA was injected into the right knee joint using a gauge 0.5 inch needle (model 750; Hamiltion Companym, Reno, NV). Osteoarthritis (MIA) was induced by injecting 50ul (MIA 3mg/body) via the infrapatellar ligament.

1500 mg/Kg microbiome mixed composition treatment group of the present invention (500 mg/kg+500 mg/kg+500 mg/kg); 500 mg/Kg celecoxib treatment group; 500 mg/kg L. Acidophilus treated group; 500 mg/kg L. rhamnosus treatment group, 500 mg/kg L. reuteri treatment group; and vehicle treatment group, each dose was orally administered per rat every day from the day after MIA induction, and the progress of 0, 3, 8, 11, 15 and 18 days was confirmed.

To measure pain in rats, a dynamic planter aesthesiometer (UgoBasile, Comerio, Itaily) was used. To measure the pain of the machine, a net plate was placed on the measuring machine, a rat was placed in an acrylic animal fixing frame on top of it, and then the right foot was stabbed with the measuring machine. After being stabbed, the time taken for the machine to automatically release the foot (s, seconds) and how much weight was applied to the foot (g) were measured, and a pain measurement graph was drawn by recording the time and weight.

As a result, as shown in FIGS. 1 and 2, as a result of confirming the behavioral experiments (paw withdrawal latency (s), paw withdrawal threshold (g), and weight on right hind rimb (%)), on the third day after the induction of osteoarthritis, each Although there was no difference in pain response in the treatment group, it was confirmed that the degree of pain response was significantly recovered in the microbiome mixture composition treatment group of the present invention compared to the Lactobacillus strain alone treatment group and the celecoxib treatment group after 8 days. .

Example 3. Cartilage protection effect of the microbiome mixture composition of the present invention

In an animal model in which osteoarthritis was induced, whether joint damage was inhibited by the microbiome mixed composition of the present invention was confirmed through CT.

As a result, as can be seen in FIG. 3, in the knee joint of the rat treated with the microbiome composition of the present invention, the damage to the knee joint was less than that of celecoxib, and the bone surface was wider, indicating an excellent cartilage protection effect. I was able to confirm.

Example 4. CTX-II inhibitory effect of the microbiome mixture composition of the present invention

Plasma was collected from the animal model in which osteoarthritis was induced as in Example 2, and CTX-II, an inflammatory marker related to cartilage damage, was measured.

As a result, as can be seen in FIG. 4, it was confirmed that the microbiome composition treatment group of the present invention showed a significantly lower CTX-II expression level than the celecoxib treatment group.

Example 5. Immunomodulatory effect of the microbiome mixture composition of the present invention

Immunomodulatory effects were confirmed in peripheral mononuclear cells of normal subjects under antiCD3 stimulation conditions. Peripheral mononuclear cells of normal subjects were treated with 1) no treatment (NIL), 2) antiCD3 and vehicle, and 3) antiCD3 and the microbiome composition of the present invention, followed by FACS and ELISA.

As a result, as can be seen in FIG. 5 , it was confirmed that Th17 cells and IL-17 were suppressed in the microbiome composition treatment group of the present invention. In addition, as shown in FIG. 6, it was confirmed that IL-17 was suppressed and IL-10 increased in the microbiome composition treatment group of the present invention.

So far, the present invention has been looked at with respect to its preferred embodiments. Those skilled in the art to which the present invention pertains will be able to understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative rather than a limiting point of view. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the equivalent scope will be construed as being included in the present invention.

Claims (9)

A pharmaceutical composition for preventing or treating osteoarthritis, comprising a mixture of strains of the genus Lactobacillus as an active ingredient,
The mixture of strains of the genus Lactobacillus is Lactobacillus reuteri, Lactobacillus rhamnosus, and Lactobacillus acidophilus at a weight ratio of 1: 1: 1 It is a complex mixture mixed in proportion,
The osteoarthritis increases the expression level of CTX-II;
IL-17 and Th17 cells are increased;
A composition having a condition in which IL-10 is reduced. delete delete delete delete delete delete The composition according to claim 1, wherein the composition inhibits Th17 cells, inhibits IL-17 and increases IL-10. A health functional food composition for preventing or improving osteoarthritis, comprising a mixture of strains of the genus Lactobacillus as an active ingredient,
The mixture of strains of the genus Lactobacillus is Lactobacillus reuteri, Lactobacillus rhamnosus, and Lactobacillus acidophilus at a weight ratio of 1: 1: 1 It is a mixed mixture,
The osteoarthritis increases the expression level of CTX-II;
IL-17 and Th17 cells are increased;
A composition having a condition in which IL-10 is reduced.

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