JP2017031120A - TNF-α AND IL-6 PRODUCTION INHIBITORS, AND MUSCLE INFLAMMATORY INHIBITORS USING THE SAME - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide novel gene silencing agents of TNF-α and IL-6 which are attributed to exercise-induced skeletal muscle damage.SOLUTION: The present invention relates to (1) a TNF-α gene silencing agent containing Kaempferia parviflora extract as an active ingredient; (2) an IL-6 gene silencing agent containing Kaempferia parviflora extract as an active ingredient; (3) an exercise-induced skeletal muscle damage-caused muscle inflammatory inhibitor which contains the agent (1) or (2) as an active ingredient; (4) a myalgia ameliorating agent containing any one of the agents (1) to (3) as an active ingredient; and (5) a muscle fatigue ameliorating agent containing any one of the agents (1) to (3) as an active ingredient.SELECTED DRAWING: None

Description

  The present invention relates to a TNF-α and IL-6 production inhibitor and a muscle inflammation inhibitor using the same.

When muscles are damaged with exercise (exercise-induced skeletal muscle injury), inflammatory reactions such as inflammatory cytokines (Tumor Necrosis Factor-α: TNF-α and Interleukin-6: IL-6) and production of active oxygen and It is known that oxidative stress is caused, and this is thought to cause muscle fatigue and pain. Here, an increase in endotoxin (toxin) concentration has been reported after exercise-induced skeletal muscle injury. Endotoxin is composed of Lipopolysaccharide (LPS), and LPS produces inflammatory cytokines such as TNF-α and IL-6.

Nitric oxide (NO) is well known as the smallest signal transduction molecule, biosynthesized from L-arginine by NO synthase (NOS), and plays an important role in healing skeletal muscle damage ( Non-patent document 1). Furthermore, NO is an important factor regarding the muscle contraction signal transduction pathway of skeletal muscle (Non-patent Document 2). On the other hand, exercise-induced skeletal muscle injury is known to induce muscle inflammation. On the other hand, various reports have been made on the action of NO in muscle inflammation. Among them, NO suppresses muscle inflammation when the muscle is already in an inflammatory state (Non-patent Document 3). Therefore, NO can be said to be a factor that plays an important role in the healing of muscle damage after exercise.

TNF-α was found as a factor that necrotizes tumors, but is recently considered to be a cytokine that plays a mediator role not only for tumors but also for regulating the function of normal cells. TNF-α plays an important role in the process from the onset to the end of inflammation, but its persistent and excessive production causes damage to tissues including the skin, and causes systemic fever and cachycecia. And cause worsening of inflammation. As such inflammation, for example, chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis are representative. Therefore, in pathological inflammation, it is important to suppress excessive production of TNF-α. Known examples of such a TNF-α production inhibitory effect include perilla extract, Japanese cypress extract, Amaryllidaceae alkaloids licorin and lycosidinol.

TNF-α also damages fibroblasts in the vicinity of subcutaneous fat and suppresses collagen and elastin production, while TNF-α promotes collagen degradation by activating collagenase. It is known.
It is also known that when muscles are damaged during exercise, TNF-α is produced, which causes various inflammations in the muscles, which cause muscle pain.

IL-6 is a cytokine produced by various tumor cells, as well as various cells such as B cells, T cells, monocytes, and fibroblasts, and is central to normal immune responses and biological defenses. (See, for example, Non-Patent Document 1, Non-Patent Document 2, and Non-Patent Document 3). Increased or decreased production of IL-6, and abnormal responsiveness to IL-6, have been suggested to be related to pathogenesis and deterioration of human inflammation, autoimmunity, and neoplastic diseases.

In addition, IL-6 is involved in so-called frame-up, in which inflammatory factors are released upon irradiation with ultraviolet light and the like, and inflammation is remarkable, and thus cancer is induced from ultraviolet damage. It is also known to be involved in the process. In addition, when muscles are damaged during exercise, IL-6 is produced, which causes various inflammations in the muscles that cause muscle pain. It has been.

Anderson JE. Mol Biol Cell. 11: 1859-74 (2000). Tatsumi R et al. Anim Sci J. 73: 235-239 (2002). Liu X et al. Int J Biol Sci. 11: 156-67 (2015). Int J Biol Sci. 2015 Jan 5; 11 (2): 156-67. Am J Physiol Regul Integr Comp Physiol. 2003 Nov; 285 (5): R1153-64.

Under such a background, the present inventor has shown that black ginger extract suppresses the expression of TNF-α and IL-6 genes in exercise-induced skeletal muscle injured muscle cells to which LPS and L-NAME are added. The present invention was completed.
That is, an object of the present invention is to provide a novel TNF-α and IL-6 gene expression inhibitor caused by exercise-induced skeletal muscle injury.

(1) A TNF-α gene expression inhibitor comprising black ginger extract as an active ingredient.
Activator.
(2) An IL-6 gene expression inhibitor comprising black ginger extract as an active ingredient.
(3) A muscle inflammation inhibitor resulting from exercise-induced skeletal muscle injury, which comprises the agent (1) or (2) as an active ingredient.
(4) A muscle pain improving agent comprising any one of the above-mentioned (1) to (3) as an active ingredient.
(5) A muscle fatigue improving agent comprising any one of the above (1) to (3) as an active ingredient.

It is a graph which shows the expression level change of the inflammatory marker (TNF- (alpha) gene and IL-6 gene) when LPS is added. It is a graph which shows the expression level change of the inflammatory marker (TNF- (alpha) gene and IL-6 gene) when L-NAME is added.

The present invention is described in detail below.
The TNF-α and IL-6 gene expression inhibitor of the present invention is characterized by using black ginger extract as an active ingredient.
The “black ginger” used in the present invention is a plant having the scientific name Kaempferia parviflora, which is distributed in Southeast Asia and belongs to the genus Kaempferia.

Used in traditional medicine such as Thailand and Laos to improve energy, improve nutrition, lower blood sugar levels, recover physical strength, improve digestive system, vaginal belt, hemorrhoids, hemorrhoids, nausea, stomatitis, joint pain, gastric pain, etc. Has been.

The black ginger used in the present invention uses a rhizome. The form of black ginger is not particularly limited, and any of immature rhizomes, fully ripe rhizomes, dry rhizomes, and the like may be used. It is also preferable to use a juice obtained by squeezing the rhizome. The form of the squeezed liquid is not particularly limited, and may be either liquid or concentrated and dried.

However, in the case of raw rhizomes or juices, care must be taken for storage, and the rhizomes are most preferably sliced and dried.

When using the dried dried rhizome, it is preferable to pulverize the rhizome to about 40 mesh in advance with a pulverizer or the like in order to increase the extraction efficiency.

The solvent and temperature conditions used for extraction are not particularly limited, and can be arbitrarily selected and set. As the extraction solvent, a non-organic solvent such as water, an acid, or a base, or an organic solvent such as a hydrophilic solvent or acetone can be selected. As the hydrophilic solvent, at least one selected from the group of lower alcohols consisting of methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol and butyl alcohol is preferable from the viewpoint of operability and extraction efficiency. However, extraction with a non-organic solvent is preferable rather than extraction with an organic solvent, and water, warm water or hot water, water with a slight addition of acid, and ethanol are particularly preferable.

The acid used at this time is not particularly limited. However, the use of acetic acid is preferred from the viewpoint of availability, safety, and post-treatment.

Further, in the above extraction, it is preferable to repeat the extraction step once or more for the extraction residue. According to this method, the extraction efficiency can be improved. The solvent used for extraction in this case may be the same or different.

The above extract can be used as it is, but it is more preferable to remove the insoluble substances and the solvent by performing treatments such as filtration, centrifugation and fractional distillation. By performing such treatment, the purity becomes higher and the application range becomes wider.
Thereafter, the extract is subjected to treatments such as dilution, concentration, drying, and purification according to a conventional method to obtain TNF-α and IL-6 gene expression inhibitors.
Examples of the purification method include activated carbon treatment, resin adsorption treatment, ion exchange resin, liquid-liquid countercurrent distribution, and the like, but they are not used in large quantities when added to foods. It may be used unpurified.

The gene expression inhibitor of TNF-α and IL-6 of the present invention can be applied to various uses for the purpose of the above-mentioned effects. Applications include pharmaceuticals, reagents, and compositions for ingestion (eg, health foods, functional foods, supplements, foods for specific uses, and supplements for pets).

The pharmaceutical composition containing the TNF-α and IL-6 gene expression inhibitor of the present invention may contain an excipient, a carrier or an additive. The excipient, carrier and additive are not particularly limited as long as they are usually used and pharmaceutically acceptable, and the type and composition thereof can be appropriately changed.

Examples of the excipient include sodium chloride and sodium citrate, and examples of the carrier include sterilized water, physiological saline, and various buffers. Examples of additives include thickeners, buffer materials, preservatives, preservatives, and the like.

The dosage form of the pharmaceutical composition is not particularly limited and may be appropriately selected as necessary. For example, oral preparations such as tablets, capsules, granules, fine granules, powders; injections And parenterals such as suppositories and coating agents.

Oral preparations such as tablets, capsules, granules, fine granules, powders and the like are produced according to a conventional method using, for example, starch, lactose, sucrose, trehalose, mannitol, carboxymethylcellulose, corn starch, inorganic salts, The compounding quantity of the compound of this invention in these formulations is not specifically limited, It can set suitably. In this type of preparation, binders, disintegrants, surfactants, lubricants, fluidity promoters, corrigents, colorants, fragrances and the like can be used as appropriate.

In the case of a parenteral preparation, the dose is adjusted according to the age, weight, disease level, etc. of the patient, and for example, intravenous administration, intravenous infusion, subcutaneous injection, intramuscular injection or the like is used. This parenteral preparation is produced according to a conventional method, and distilled water for injection, physiological saline and the like can be generally used as a diluent. Furthermore, you may add a bactericidal agent, antiseptic | preservative, a stabilizer, etc. as needed. In addition, from the viewpoint of stability, this parenteral preparation can be frozen after filling into a vial or the like, the water can be removed by ordinary freeze-drying treatment, and the liquid preparation can be re-prepared from the freeze-dried product immediately before use. Further, if necessary, an isotonic agent, a stabilizer, an antiseptic, a soothing agent and the like may be added. Examples of other parenteral agents include liquid preparations for external use, coating agents such as ointments, suppositories for rectal administration, etc., and these are also produced according to conventional methods.

When the present invention is used for health foods (including functional indication foods, foods for specified health use, health drinks and supplements), the compound of the present invention is added to the health foods as raw materials for various health foods, or dextrin as necessary It can be processed into pellets, tablets, granules, etc. together with excipients such as lactose and starch, fragrances, pigments, etc., or coated with gelatin and formed into capsules to produce health foods.

The mixing ratio of the gene expression inhibitor of TNF-α and IL-6 to be blended in health food is not particularly limited as long as the expected effect of the gene expression inhibitor of TNF-α and IL-6 can be obtained. However, the intake per time is usually about 0.0001 to 2000 mg.

These health foods can be blended with various components depending on the type, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, Succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic Food materials such as carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances and preservatives can be used. Furthermore, TNF-α and IL-6 gene expression inhibitors having a health maintenance function include other antioxidants and health food ingredients such as antioxidants (reduced ascorbic acid (vitamin C)). , Vitamin E, reduced glutatin, tocotrienol, vitamin A derivative, lycopene, lutein, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sesamin, lignans, catechin, isoflavone, chalcone, Tannins, flavonoids, coumarins, isocoumarins, blueberry extract), health food ingredients (V. (vitamin) A, V.B1, V.B2, V.B6, V.B12, VC, VD, VE, VP, Choline, niacin, pantothenic acid, calcium folate, EPA, oligosaccharide, dietary fiber, squalene, soybean lecithin , Taurine, donariella, protein, octacosanol, DHA, egg yolk lecithin, linoleic acid, lactoferrin, magnesium, zinc, chromium, selenium, potassium, heme iron, oyster meat extract, chitosan, chitin oligosaccharide, collagen, chondroitin, turmeric, licorice, Kukosi, Keihi, Hawthorn, Ginger, Ganoderma, Shijimi extract, Suppon, Chamomile, Chamomile, Atlantic dandelion, Hibiscus, Honey, Boren, Royal jelly, Lime, Lavender, Rosehip, Rosemary, Bifidobacterium, Fecaris, Lacris, Wheat germ Oil, sesame oil, perilla oil, soybean oil, medium chain fatty acid, agaricus, ginkgo biloba extract, turmeric, chondroitin, brown rice germ extract, litchi, onion, DPA, strawberry tea, cordyceps, garlic, bee, papaya, -Al, Propolis, Meguri Tree, Yabushake, Saw Palmetto, Hyaluronic Acid, Collagen, Gabba, Harp Seal Oil, Shark Cartilage, Glucosamine, Lecithin, Phosphatidylserine, Rice Carrot, Mulberry Leaf, Soybean Extract, Echinacea, Ezoukogi, Barley Extract , Olive leaf, olive fruit, gymnema, banaba, salacia, garcinia, chitosan, st jones wort, jujube, carrot, passion flower, broccoli, placenta, pearl barley, grape seed, peanut seed coat, bilberry, black cohosh, maria thistle, laurel, sage , Rafuma, black vinegar, bitter gourd, maca, safflower, flax, oolong tea, flower spine, caffeine, capsaicin, xylooligosaccharide, glucosamine, buckwheat, citrus, dietary fiber, protein, prune Lurina, barley young leaves, nucleic acid, yeast, shiitake mushroom, plum meat, amino acid, deep-sea cocoon extract, noni, oyster meat, champignon, plantain, acerola, pineapple, banana, peach, apricot, melon, strawberry, raspberry, orange, fucoidan, Meshimakobu, Cranberry, Chondroitin Sulfate, Zinc, Iron, Ceramide, Silk Peptide, Glycine, Niacin, Chest Tree, L-Cysteine, Red Wine Leaf, Millet, Horsetail, Biotin, Centella Asiatica, Hascup, Pycnogenol, Fuki, Rhubarb, Clove, catechin, puer, citric acid, brewer's yeast, merirot, black zinger, ginger, garlic, nattokinase, benicozi, tocotrienol, lactoferrin, cinnamon, buckwheat, cocoa, yuzu seed extract, perilla Extract, lychee seed extract, evening primrose extract, black rice extract, α-lipoic acid, fresh coffee bean extract, mandarin orange extract, triterpenoid, kiwi seed extract, red ginger extract, astaxanthin, walnut extract, resveratrol, red rice extract, white jellyfish Polysaccharides, strawberry seed extract, strawberry seed extract, leek seed extract, lingon berry extract, cherry blossom extract, Sasa Kurihito Yotake extract, maqui berry extract, rice polyamine, wheat polyamine) and the like.

When the present invention is used as a health food, the TNF-α and IL-6 gene expression inhibitor of the present invention can be used as a dosage form for various general foods and beverages.
Here, “can be used as a dosage form of various general foods and drinks” is generally used as a dosage form for the purpose of exerting the effect of the gene expression inhibitor of TNF-α and IL-6 of the present invention. It means that food and drink can be selected, and is intended only for those who wish to have an effect as a gene expression inhibitor of TNF-α and IL-6. It does not mean that it can be eaten widely by everyone, including those who do not expect an effect as a gene expression inhibitor.
Moreover, although the compounding quantity for exhibiting an effect as a gene expression inhibitor of TNF- (alpha) and IL-6 is not specifically limited, It is preferable that the content of an active ingredient is 1-20 wt% in total with respect to food-drinks.
Moreover, although it does not specifically limit as general food / beverage products to mix | blend, For example, edible oil (salad oil), confectionery (gum, candy, caramel, chocolate, cookie, snack, jelly, gummi, tablet confection etc.), noodles (soba, Udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, tea, tea, carbonated drinks, sports drinks, etc.) It is done.

  In these general foods and drinks, various components can be blended depending on the type, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, Succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic Food materials such as carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances and preservatives can be used. Further, the present TNF-α and IL-6 gene expression inhibitors having health maintenance functions include other antioxidants and health food ingredients such as antioxidants (reduced ascorbic acid (vitamin C). ), Vitamin E, reduced glutatin, tocotrienol, vitamin A derivatives, lycopene, lutein, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sesamin, lignans, catechin, isoflavone, chalcone , Tannins, flavonoids, coumarin, isocoumarins, blueberry extract), health food ingredients (V. (vitamin) A, V.B1, V.B2, V.B6, V.B12, VC, VD, VE, VP , Choline, niacin, pantothenic acid, calcium folate, EPA, oligosaccharide, dietary fiber, squalene, soybean lecithin , Taurine, donariella, protein, octacosanol, egg yolk lecithin, linoleic acid, lactoferrin, magnesium, chromium, selenium, potassium, heme iron, oyster meat extract, chitosan, chitin oligosaccharide, collagen, chondroitin, turmeric, licorice, kokushi, kehi , Hawthorn, ginger, ganoderma, swordfish extract, licorice, kokushi, keihi, hawthorn, ginger, ganoderma, plantain, chamomile, chamomile, dandelion, hibiscus, honey, boren, royal jelly, lime, lavender, rose hip, rosemary, Sage, bifidobacteria, faecalis, lacris, wheat germ oil, sesame oil, perilla oil, soybean oil, medium chain fatty acid, agaricus, ginkgo biloba extract, turmeric, chondroitin, brown rice germ extract, litchi, onion, DHA EPA, DPA, green tea, cordyceps, garlic, bee, papaya, puer, propolis, meguri tree, yabushitake, royal jelly, saw palmetto, hyaluronic acid, collagen, gab, harp seal oil, shark cartilage, glucosamine, lecithin, phosphatidyl Serine, seven carrots, mulberry leaves, soybean extract, Echinacea, Ezoukogi, barley extract, olive leaf, olive fruit, gymnema, banaba, Salacia, Garcinia, chitosan, St. John's wort, jujube, carrot, passion flower, broccoli, placenta , Pearl barley, grape seed, peanut seed coat, bilberry, black cohosh, maria thistle, laurel, sage, rosemary, raffma, black vinegar, bitter gourd, maca, safflower, flax, oolong tea, flower thorn, caffeine, capsaici , Xylo-oligosaccharide, glucosamine, buckwheat, citrus, dietary fiber, protein, prunes, spirulina, barley young leaves, nucleic acid, yeast, shiitake, plum meat, amino acids, deep sea potato extract, noni, oyster meat, suppon, champignon, plantain, Acerola, pineapple, banana, peach, apricot, melon, strawberry, raspberry, orange, fucoidan, meshimakobu, cranberry, chondroitin sulfate, zinc, iron, ceramide, silk peptide, glycine, niacin, chest tree, L-cysteine, red wine leaf, Millet, Horsetail, Biotin, Centella Asiatica, Lotus Cup, Pycnogenol, Fuqui, Rhubarb, Clove, Rosemary, Catechin, Pual, Citric Acid, Beer Yeast, Merirot, Black Zinger, Ginger, Gadju, Nut Ukinase, Benikouji, Tocotrienol, Lactoferrin, Cinnamon, Persimmon Buckwheat, Cocoa, Yuzu Seed Extract, Perilla Seed Extract, Lychee Seed Extract, Evening Primrose Extract, Black Rice Extract, α-Lipoic Acid, Gabba, Fresh Coffee Bean Extract, Fuquisa Extract, Kiwi Seed Extract, Wenzhou mandarin orange extract, red ginger extract, astaxanthin, walnut extract, leek seed extract, red rice extract, kanka extract, white jellyfish polysaccharide, fucoxanthin, lingonberry extract, cherry blossom extract, maquiberry extract, Japanese cherry extract, rice polyamine , Wheat polyamine) and the like.

  As a specific production method, TNF-α and IL-6 gene expression inhibitors are spray-dried or freeze-dried together with powdered cellulose, and this is easily converted into powders, granules, tablets or solutions, so that the general food and drink ( Instant foods). Moreover, it is possible to dissolve the gene expression inhibitor of TNF-α and IL-6 in, for example, fats and oils, ethanol, glycerin, or a mixture thereof, and add them to beverages or to solid foods. . If necessary, it can be mixed with a binder such as gum arabic or dextrin to form a powder or granules and added to a beverage or a solid food.

Hereinafter, the present invention will be described based on examples.
Examples: Test sample (1) Preparation of black ginger extract Black ginger was sliced and dried to obtain 100 kg of a dried product. 10 kg of this dried product was crushed and extracted at 80 ° C. with hydrous ethanol having an ethanol concentration of 70 wt% for 2 hours, and the ethanol extract was dried to obtain 3.25 kg of black ginger extract.
The components contained in the black ginger extract were analyzed by HPLC. As a result, it was found that the content of 5,7-dimethoxyflavone was 8 wt% or more and the total flavonoid was 35 wt% or more.

Test example: Evaluation of IL-6 and TNF-α gene expression-suppressing action caused by exercise-induced skeletal muscle injury (1) Test method Mouse myoblast cell line C2C12 is seeded on a 24-well plate (1 × 104 cells / mL) For 7 days, black ginger extract was added at a concentration of 1,3,10 μg / mL, and differentiation induction treatment was performed at the same time. After culturing for 7 days, LPS (final concentration: 1 μg / mL) or L-NAME (final concentration: 10 μM) was added and cultured for 1 hour. After 1 hour, the cells were collected and RNA was extracted. The expression level of inflammation marker genes (IL-6, TNF-α) was quantitatively analyzed for the obtained RNA by quantitative RT-PCR. At this time, the relative expression level of each gene was corrected by GAPDH. The results are shown in FIG. 1 (LPS added) and FIG. 2 (L-NAME added).

(2) Results and Effects of Examples As shown in FIG. 1, it was confirmed that black ginger extract (KPE) suppresses the expression of TNF-α and IL-6 genes by LPS.
Furthermore, as shown in FIG. 2, it was confirmed that the expression of TNF-α and IL-6 genes by L-NAME was suppressed. Thereby, it was confirmed that it is useful as a TNF-α and IL-6 gene expression inhibitor caused by LPS and L-NAME (that is, exercise-induced skeletal muscle injury).
From the above results, the black ginger extract has the effect of reducing muscle inflammation and muscle pain caused by exercise-induced skeletal muscle injury, and the muscle inflammation inhibitor caused by exercise-induced skeletal muscle injury, and this It was confirmed that it can be used as a muscle pain improving agent and a muscle fatigue improving agent.

Although the compounding example of the gene expression inhibitor (black ginger extract) of TNF- (alpha) and IL-6 of this invention is given to the following, the following compounding example does not limit this invention.
Formulation Example 1: Chewing gum (functional indication food or food for specified health use)
53.0wt% sugar
Gum base 20.0
Glucose 10.0
Minamata 16.0
Fragrance 0.5
Black ginger extract 0.5
100.0wt%

Formulation Example 2: Gummy (Functional indication food or food for specified health use)
Reduced water tank 40.0wt%
Granulated sugar 20.0
Glucose 20.0
Gelatin 4.7
Water 9.68
Kiwi juice 4.0
Kiwi flavor 0.6
Dye 0.02
Black ginger extract 1.0
100.0wt%

Formulation example 3: Candy (functional indication food or food for specified health use)
50.0 wt% sugar
Minamata 33.0
Water 14.4
Organic acid 2.0
Fragrance 0.2
Black ginger extract 0.4
100.0wt%

Formulation Example 4: Yogurt (hardware / soft) (functional food or food for specified health use)
Milk 41.5wt%
Nonfat dry milk 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Black ginger extract 0.4
Perfume
Water residue
100.0wt%

Formulation Example 5: Soft drink (functional display food or food for specified health use)
Fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
Black ginger extract 0.05
Perfume
Purified water residue
100.0 wt%

Formulation Example 6: Soft capsule (functional indication food or food for specified health use)
Rice germ oil 87.0wt%
Emulsifier 12.0
Black ginger extract 1.0
100.0wt%

Formulation Example 7: Tablet (Functional indication food or specified health food)
Lactose 54.0wt%
Crystalline cellulose 30.0
Starch degradation product 10.0
Glycerin fatty acid ester 5.0
Black ginger extract 1.0
100.0wt%

Formulation Example 8: Oral granules (pharmaceuticals)
Black ginger extract 1.0wt%
Lactose 30.0
Cornstarch 60.0
Crystalline cellulose 8.0
Polyvinylpyrrolidone 1.0
100.0wt%

Formulation Example 9: Tablet
76.4 wt% sugar
Glucose 19.0
Sucrose fatty acid ester 0.2
Black ginger extract 0.5
Purified water 3.9
100.0wt%

Formulation Example 15: Cat food
Corn 34.0wt%
Flour 35.0
Meat meal 15.0
Beef tallow 8.9
Salt 1.0
Skipjack extract 4.0
Black ginger extract 1.0
Taurine 0.1
Vitamins 0.5
Minerals 0.5
100.0wt%

Formulation Example 16: Dog food
Corn 30.0wt%
Meat (chicken) 15.0
Defatted soybean 10.0
Flour 25.0
Mosses 5.0
Black ginger extract 5.0
Animal fats and oils 8.9
Oligosaccharide 0.1
Vitamin 0.5
Mineral 0.5
100.0wt%

  As described above, the present invention can provide a TNF-α and IL-6 gene expression inhibitor that is safe and has few side effects.

Claims (5)

A TNF-α gene expression inhibitor comprising black ginger extract as an active ingredient.
Activator. An IL-6 gene expression inhibitor comprising black ginger extract as an active ingredient. An agent for inhibiting muscle inflammation caused by exercise-induced skeletal muscle injury, comprising the agent according to claim 1 or 2 as an active ingredient. The muscular pain improving agent which uses any one agent of Claims 1-3 as an active ingredient. The muscular fatigue improving agent which uses any one agent of Claims 1-3 as an active ingredient.

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