JP2017193497A - Muscle enhancer - Google Patents

Abstract

An object of the present invention is to provide a novel muscle building agent. [Solution]1. A muscle differentiation-inducing promoter comprising, as an active ingredient, a fermented extract obtained by fermenting rice bran and/or rice germ to obtain a fermented product, and then extracting the fermented rice product with a polar solvent. 2. 1 above. A muscle differentiation-inducing promoter comprising, as an active ingredient, a distribution obtained by distributing the above-described fermented extract described in 1. with a polar solvent. 3. A muscle differentiation induction promoter containing at least one compound selected from stigmasterol, ergosterol peroxide, β-sitosterol glucoside and glucosylceramide as an active ingredient. 4. A muscle bulking agent comprising, as an active ingredient, a fermented extract obtained by fermenting rice bran and/or rice germ to obtain a fermented product, and then extracting the fermented rice product with a polar solvent. 5. 4 above. A muscle bulking agent comprising, as an active ingredient, a distribution obtained by distributing the fermented extract described in 1. above with a polar solvent. 6. A muscle bulking agent containing stigmasterol as an active ingredient. [Selection figure] None

Description

The present invention relates to a muscle strengthening agent comprising a novel ingredient as an active ingredient. The present invention can be widely used for foods and drinks (health foods, foods for specified health use, functional display foods), quasi drugs, pharmaceuticals, and the like.

Aspergillus has long been used in the production of sake, miso, and soy sauce in Japan, and is an indispensable fungus for our lives. These fermented products are attracting attention as functional foods as well as mere foods, and various physiologically active substances may be newly produced with fermentation.

On the other hand, sphingolipids are known to have functions such as skin moisturizing effect, moisture control, elasticity retention, surface protection (barrier effect), collagen protection, and antioxidant (stabilization of vitamins C and E). Widely used in the field. Recently, it has become clear that the action of sphingolipids prevents the entry of antigens from the outside world into the body and suppresses atopic dermatitis, and development as a pharmaceutical is being promoted.

As a method for producing a sphingolipid-containing composition from rice, for example, a method is known in which a gum obtained in the production process of rice bran oil is defatted with an organic solvent, and the defatted product is extracted with water or alcohol ( Patent Document 1).

On the other hand, it is known that blood cholesterol is lowered by ingestion of phytosterols. Phytosterols are plant sterols found in small amounts in vegetable oils such as corn, beans or other vegetable oils, which occur as free sterols, fatty acid esters and glycosides. Phytosterols are structurally similar to cholesterol, with the main difference occurring in the carbon skeleton of their side chains. Many different phytosterol structures have been found in nature. The most common are campesterol, beta-sitosterol and stigmasterol. In particular, stigmasterol has a remarkable effect of lowering cholesterol in blood (Non-patent Document 1).

Japanese Patent Application Laid-Open No. 2005-73502 (Patent Document 2) describes a food or a food material having an apoptosis-inducing ability, which is made of a mushroom extract obtained by extracting mushroom. In addition, the publication describes that this mushroom extract exhibits a suppressive and preventive effect on cancer, and that the food or food material having the ability to induce apoptosis is composed of ergosterol peroxide derived from mushroom. ing.

On the other hand, the following problems were tried for the purpose of comprehensively preventing and treating diseases derived from lifestyle-related diseases. We have already found resveratrol that causes longevity gene activation in polyphenols that specifically contain quercetin and chlorogenic acid in a large amount together with the hypoglycemic effect (Japanese Patent Application No. 2011-90489) over mulberry leaf powder in mulberry stem powder. Furthermore, the evening primrose powder containing a large amount of β-sitosterol glycosides that have a strong hemostatic action against bleeding caused by vascular leaky disease is caused by lifestyle-related diseases such as hyperglycemia, hypertension and hyperlipidemia It is known to have a comprehensive preventive effect against sexually transmitted diseases.

JP 2001-97983 A JP-A-2005-73502 Batta et al. 2006, Metabolism Clinical and Experimental 55: 292-29

Under such a background, the present inventors have found that glucosylceramide, stigmasterol, ergosterol peroxide, and β-sitosterol glycoside obtained by fermenting rice bran and rice germ have a muscle-enhancing action. The present invention has been completed.
That is, an object of the present invention is to provide a novel muscle strengthening agent.

The technical features of the present invention for solving the above-described problems are as follows.
1. A muscle differentiation induction promoter comprising a fermented extract obtained by fermenting rice bran and / or rice germ to obtain a fermented product, and then extracting the fermented rice product with a polar solvent.
2. Above 1. A muscle differentiation-inducing promoter comprising as an active ingredient a distribution obtained by distributing the fermentation extract described in 1 above with a polar solvent.
3. A muscle differentiation induction promoter comprising as an active ingredient at least one compound selected from stigmasterol, ergosterol peroxide, β-sitosterol glucoside, and glucosylceramide.
4). A muscle bulking agent comprising a fermented extract obtained by fermenting rice bran and / or rice germ to obtain a fermented product, and then extracting the fermented rice product with a polar solvent.
5). 4. above. A muscle bulking agent comprising, as an active ingredient, a distribution obtained by distributing the fermentation extract described in 1 above with a polar solvent.
6). A muscle bulking agent containing stigmasterol as an active ingredient.
7). A muscle weight gain gene expression promoter comprising a fermented extract obtained by fermenting rice bran and / or rice germ to obtain a fermented product, and then extracting the fermented rice product with a polar solvent.
8). Above 7. A muscle weight gain gene expression promoter comprising as an active ingredient a distribution obtained by distributing the fermentation extract described in 1 above with a polar solvent.
9. A muscle weight gain gene expression promoter comprising at least one of stigmasterol and glucosylceramide as an active ingredient.
10. A muscle contraction power improver comprising as an active ingredient a fermented extract obtained by fermenting rice bran and / or rice germ to obtain a fermented product, and then extracting the fermented rice product with a polar solvent.
11. 10. above. A muscle contraction force improver comprising as an active ingredient a distribution obtained by distributing the fermentation extract described in 1 above with a polar solvent.
12 A muscle contraction force improver containing glucosylceramide as an active ingredient.
13. Above 1. -12. A muscle strengthening agent comprising the above agent as an active ingredient.

It is a schematic diagram which shows the method of isolating Compound 1-5 from a rice germ fermentation extract. It is a graph which shows the result of the comparison test with the rice origin protein in differentiation induction promotion. It is a graph which shows the evaluation result of the muscle differentiation induction promotion effect by a premature differentiation marker (myogenin). It is a graph which shows the evaluation result of the muscle differentiation induction promotion effect by a mature differentiation marker (MyHP). It is a graph which shows the result of the comparison test with the unfermented rice germ fermentation extract and rice origin protein in a myocyte proliferation promotion effect. It is a graph which shows the evaluation result of a myocyte proliferation promotion effect. It is a graph which shows the evaluation result of muscle weight gain gene IGF-1 expression promotion activity. It is a graph which shows a muscular contraction promoting action evaluation result.

The present invention is described in detail below.
The present invention is characterized in that a fermented product obtained by fermenting rice bran and / or rice germ to obtain a fermented product and then extracting the fermented rice product with a polar solvent is used as an active ingredient.

For “rice bran and / or rice germ”, ginger produced in the rice milling process of brown rice may be used. Brown rice is composed of pericarp, seed coat, endosperm and germ, and there is a thin layer called a paste layer on the outer layer of the endosperm tissue.
As the milling progresses, not only the pericarp and seed coat, but also the glue layer is eliminated as rice bran (ginger). If necessary, a mixture of pericarp, seed coat, rice germ or paste can be used, or a mixture of pericarp, seed coat, rice germ or paste can be used.

The rice bran and / or rice germ is preferably used with a defatted one. This is because a composition containing a higher concentration of the active ingredient can be obtained. This degreasing method is not particularly limited,
At this time, preferable degreasing solvents include n-hexane, acetone and the like. In particular, n-hexane is preferably used as a degreasing solvent. This is because the extracted oil can be used as an edible oil, and the rice germ fermented extract can be easily used as a food material.
These degreasing solvents may be used alone or in combination of two or more.
Microorganisms used in the above “fermentation” are not particularly limited, and koji molds, yeasts, citric acid bacteria, lactic acid bacteria, acetic acid bacteria, and the like can be used. Of these, Neisseria gonorrhoeae is preferred.
Although it does not specifically limit as said "gonococcus", For example, the 1 or more thing chosen from sake for sake, shochu, awamori, miso, or soy sauce can be used.
For example, Aspergillus kawachii, Aspergillus awamori, Aspergillus oryzae, Aspergillus sojae, Aspergillus sasperi (Aspergillus saitoi), Aspergillus sasperi (Aspergillus sasperi) One or more selected. Although the temperature of fermentation is not specifically limited, 10-60 degreeC, Furthermore, 20-40 degreeC, Especially 25-35 degreeC is preferable. It is because it is the optimal temperature for the fermentation by Aspergillus to progress by setting it as these ranges.
Moreover, fermentation time is not specifically limited, It is preferable to carry out for 1 to 7 days, and also for 2 to 4 days.

As the “polar solvent”, polar solvents such as water, methanol, ethanol, isopropyl alcohol, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, and ethyl acetate can be used. Two or more of these solvents may be mixed.
Desirably, when water ethanol or water-containing ethanol, which is a mixture thereof, is used as an extraction solvent, the active ingredient is efficiently extracted.

  When hydrous ethanol is used as the extraction solvent, the ethanol concentration is not particularly limited, but in particular, the ethanol concentration is 10 to 90% (wt / wt), and desirably the ethanol concentration is 20 to 80% (wt / wt). The reason why the ethanol concentration is 90% (wt / wt) or less is that if the ethanol concentration is too high, the oil content of the fermentation extract is likely to dissolve in the water-containing ethanol.

  The extraction temperature is 20 to 80 ° C, preferably about 40 to 50 ° C. This is because if the extraction temperature is too low, it becomes difficult to extract the active ingredient, and if the extraction temperature is too high, the active ingredient is decomposed and the physiological activity (health functionality) is reduced.

  As the extraction method, any method such as stirring extraction, continuous extraction, immersion extraction, countercurrent extraction, and supercritical extraction can be employed, and any apparatus can be used at room temperature or under reflux heating.

Moreover, although the said fermentation extract may be used as it is for this invention, what distributed the fermentation extract with the polar solvent for liquid separation after that can also be used.
The method of “distribution” is not particularly limited, but liquid-liquid distribution is preferably performed. The solvent used in the liquid-liquid distribution is not particularly limited, and for example, water, methanol, ethanol, isopropyl alcohol, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, hexane, ethyl acetate, chloroform and the like can be used. Of these, hexane, methanol, and chloroform are preferably used.

Compounds such as stigmasterol, ergosterol peroxide, β-sitosterol glucoside, glucosylceramide, and the like can be obtained by the above method, but are not limited thereto. In addition, these may use what isolated only 1 type of compound, and may use these mixtures or a crude thing.

Further, the present invention is characterized in that any one of stigmasterol, ergosterol peroxide, β-sitosterol glucoside, and glucosylceramide is an active ingredient.
The method for obtaining the compound is not particularly limited, but can be obtained by purifying and isolating the fermented product as described above.

The present invention can be applied to various uses. 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 comprising the present invention may contain excipients, carriers or additives. 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 Suppositories,
Examples include parenteral agents such as 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. Furthermore, you may add a tonicity agent, a stabilizer, antiseptic | preservative, a soothing agent, etc. as needed. 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 muscle enhancer compounded in the health food is not particularly limited as long as the effect expected from the muscle enhancer can be obtained. Usually, the amount per one intake is about 0.0001 to 2000 mg. is there.

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. In addition, muscle enhancers with 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 derivative, lycopene, lutein, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sesamin, lignans, catechin, isoflavone, chalcone, tannins, flavonoids, coumarin, isocoumarin , 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, soy 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, kokushi, kehi, hawthorn , Ginger, ganoderma, swordfish extract, suppon, chamomile, chamomile, dandelion, hibiscus, honey, bowlen, royal jelly, lime, lavender, rosehip, rosemary, 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, DPA, green tea, cordyceps, garlic, bee, papaya, puer, propolis, megsuri , Yabushitake, Saw Palmetto, Hyaluronic Acid, Collagen, Gabba, Harp Seal Oil, Shark Cartilage, Glucosamine, Lecithin, Phosphatidylserine, Tabuchi Carrot, Mulberry Leaf, 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, barley, grape seed, peanut seed coat, bilberry, black cohosh, Maria thistle, laurel, sage, raffma, black vinegar, goya , Maca, safflower, flax, oolong tea, flower spine, caffeine, capsaicin, xylo-oligosaccharide, glucosamine, buckwheat, citrus, dietary fiber, protein, prune, spirulina, barley young leaf, nucleic acid, yeast, Salmon, plum meat, amino acid, deep-sea coral extract, noni, oyster meat, champignon, plantain, acerola, pineapple, banana, peach, apricot, melon, strawberry, raspberry, orange, fucoidan, mesimacob, 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, Beer yeast, Merirot, Black Zinger, Ginger, Gadju, Nattokinase, Benikouji, Tocotrienol, Lactoferrin, Cinnamon, Persimmon buckwheat, Cocoa, Yuzu seed extract, Perilla seed extract, Lychee seed extract, Moon viewing Extract, black rice extract, α-lipoic acid, fresh coffee bean extract, Unshu mandarin orange extract, triterpenoid, kiwi seed extract, red ginger extract, astaxanthin, walnut extract, resveratrol, red rice extract, white fungus polysaccharide, strawberry seed extract, Strawberry seed extract, leek seed extract, lingonberry extract, cherry blossom extract, Sasa Kurihito Yotake extract, maki berry extract, rice polyamine, wheat polyamine, black ginger extract, Junsai extract, swallow nest extract, purple tea extract, chrysanthemum flower Extract, seaberry extract) and the like.

When the present invention is used as a health food, the muscle enhancer can be used as a dosage form for various general foods and drinks. Here, “can be used as a dosage form for various general foods and drinks” means that a general food and drink can be selected as a dosage form for the purpose of exerting the effect as the muscle strengthening agent. It is intended to be eaten only by those who desire the effect expected from the muscle enhancer, and means that it can be eaten widely by everyone including those who do not expect the effect as the muscle enhancer. is not.
Moreover, although the compounding quantity for exhibiting an effect as said muscle strengthening agent 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. Furthermore, the above-mentioned muscle-enhancing agent having a health maintenance function includes 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, 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, folic acid Calcium, EPA, oligosaccharide, dietary fiber, squalene, soy lecithin, taurine, donariella, Lotein, octacosanol, egg yolk lecithin, linoleic acid, lactoferrin, magnesium, chromium, selenium, potassium, heme iron, oyster meat extract, chitosan, chitin oligosaccharide, collagen, chondroitin, turmeric, licorice, kokushi, cahi, hawthorn, ginger, spirit Turf, swordfish extract, licorice, kokushi, keihi, hawthorn, ginger, ganoderma, plantain, chamomile, chamomile, dandelion, hibiscus, honey, boren, royal jelly, lime, lavender, rosehip, rosemary, sage, bifidobacteria, faecalis Fungus, 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, mugwort tree, jabushitake, royal jelly, saw palmetto, hyaluronic acid, collagen, gabba, harp seal oil, shark cartilage, glucosamine, lecithin, phosphatidylserine, paddy carrot, mulberry leaves , Soybean extract, Echinacea, Ezoukogi, Barley extract, Olive leaf, Olive fruit, Gymnema, Banaba, Salacia, Garcinia, Chitosan, St. John's wort, jujube, carrot, passionflower, 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 spine, caffeine, capsaicin, xylooligosaccharide, gluco Min, buckwheat, citrus, dietary fiber, protein, prunes, spirulina, barley young leaves, nucleic acid, yeast, shiitake mushroom, plum meat, amino acids, deep sea potato extract, noni, oyster meat, suppon, champignon, plantain, acerola, pineapple, banana Peach, apricot, melon, strawberry, raspberry, orange, fucoidan, mesimacob, cranberry, chondroitin sulfate, zinc, iron, ceramide, silk peptide, glycine, niacin, chestnut tree, L-cysteine, red wine leaf, millet, horsetail, Biotin, Centella Asiatica, Hascup, Pycnogenol, Japanese cypress, rhubarb, clove, rosemary, catechin, puer, citric acid, brewer's yeast, merirot, black zinger, ginger, gadget, nattokinase, benicouji, tomato Trienol, lactoferrin, cinnamon, buckwheat 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, burdock extract, kiwi seed extract, Unshu mandarin orange Extract, red ginger extract, astaxanthin, walnut extract, leek seed extract, red rice extract, kanka extract, white fungus polysaccharide, fucoxanthin, lingonberry extract, cherry blossom extract, maquiberry extract, cherry salmon extract, rice polyamine, wheat polyamine, Black ginger extract, Junsai extract, swallow nest extract, purple tea extract, chrysanthemum flower extract, sea berry extract) and the like can also be blended.

  As a specific production method, the above-described muscle-enhancing agent is spray-dried or freeze-dried together with powdered cellulose, and this is easily converted into a powder, granule, tablet, or solution. Can also be included). In addition, the above-described muscle enhancer can be dissolved in oil, fat, ethanol, glycerin or a mixture thereof to form a liquid and added to a beverage or added to a solid food. 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.

Example: Isolation of fermented rice germ extract and active ingredients (1) Preparation of fermented rice germ extract 1.4 kg of defatted rice germ and an equivalent amount of distilled water were mixed and sterilized in an autoclave, and 560 mg of koji mold and decoction A mixture of 42 g added and fermented was fermented under conditions of 35 ° C. for 3 days to obtain a koji mold fermented rice germ. This fermented rice germ was subjected to warm extraction with 3 kg of methanol three times, and the extract was concentrated under reduced pressure to obtain 156.06 g of a methanol extract (fermented rice germ extract).
(2) Isolation of active ingredient The methanol extract (83 g) was separated sequentially with hexane, ethyl acetate, chloroform: methanol = 6: 1, 17.67 g of hexane soluble part, 5.73 g of ethyl acetate soluble part, Chrometa The soluble part 3.73 g was obtained. Each soluble part was fractionated according to the fractionation scheme of FIG. 1, and the five components of Compound 1-5 were isolated. Structural analysis by NMR was performed on the five isolated components. Of these, Compound 1, 2, 4, and 5 were subjected to structural analysis.
Here, the chemical formulas of Compound 1, 2, 4, and 5 are shown below.

Test Example 1: Promotion of muscle differentiation induction (1) Test in rice germ fermentation extract Rice germ fermentation extract was added to mouse myoblast C2C12 at a concentration of 1-100 μg / mL, and differentiation induction was performed at the same time. It was. After culturing for one week, the cells were collected, and the mRNA expression levels of myogenin, a muscle premature differentiation marker, and myosin, heavy polypeptide (MyHP), were quantitatively analyzed. At that time, GAPDH was used as an endogenous control for correction. In addition, as a comparative example, the same test was conducted on rice extract that does not have a fermentation process and oryza protein (produced by Oriza Oil Chemical Co., Ltd.), which is a rice-derived protein without a fermentation process. The result is shown in FIG.
(2) Test on isolated component In the same manner as described above, the component (Compound. 1-5) isolated from the fermented rice germ extract was tested at a concentration of 1 and 10 µg / mL. The results are shown in FIG. 3 (myogenin) and FIG. 4 (MyHP).

Effect of Example in Test Example 1 As shown in FIG. 2, myocyte proliferation was significantly promoted by the fermented rice germ extract. In addition, IGF-1, which is a positive control, also proliferated significantly. In addition, unfermented rice germ extract has an effect of suppressing cell growth, and rice-derived protein (Oryza protein), which is an unextracted rice extract, has a muscle growth promoting effect compared to rice germ fermented extract. It was weak. From the above, it was confirmed that fermenting rice germ can provide a muscle strengthening effect that has never existed before, and it is stronger than protein intake.
Moreover, as shown in FIG. 3, expression was promoted by adding Compound 1-5 (1 and 10 μg / mL) in myogenin, a marker for early differentiation of muscle. In particular, expression was significantly promoted by the addition of Compound 1 (1 μg / mL) and Compound 5 (1 and 10 μg / mL). On the other hand, as shown in FIG. 4, in MyHP, a muscle maturation differentiation marker, Compound 1 (1 and 10 μg / mL), Compound 3 (10 μg / mL), Compound 4 (1 μg / mL), Compound 5 (1 And 10 μg / mL) promoted expression. In particular, expression was significantly promoted by the addition of Compound 1 (1 μg / mL) and Compound 5 (10 μg / mL). From the above, it was confirmed that Compound 1-5 has an activity of promoting the induction of muscle differentiation in premature and mature stages. From the above, it was confirmed that the fermented rice germ extract and Compound 1-5 function as muscle differentiation induction promoters.

Test Example 2: Muscle cell proliferation promoting action (muscle mass increasing action)
(1) Evaluation using rice-fermented rice germ extract Rice fermented rice germ extract and mouse-derived protein (Oryza protein) as a comparative example were added to mouse myoblast C2C12 at 1-100μg / mL, and differentiation was induced at the same time. Went. After culturing for 1 week, MTT assay was performed to evaluate the effect on cell proliferation. In addition, as a comparative example, the same test was conducted on rice extract that does not have a fermentation process and oryza protein (produced by Oriza Oil Chemical Co., Ltd.), which is a rice-derived protein without a fermentation process. The result is shown in FIG.
(2) Evaluation by isolated components To rice myoblasts C2C12, a rice germ ferment extract and a component isolated from rice germ ferment extract (Compound 1) were added at a concentration of 0.1-30 μg / mL, and differentiation was induced at the same time. Went. After culturing for 1 week, MTT assay was performed to evaluate the effect on cell proliferation. The result is shown in FIG.

Effect of Example in Test Example 2 As shown in FIG. 5, myocyte proliferation was significantly promoted by the fermented rice germ extract. In addition, IGF-1, which is a positive control, also proliferated significantly. In addition, the unfermented rice germ extract exhibited an effect of suppressing cell growth, and the rice-derived protein had a weaker muscle growth promoting effect than the rice germ fermented extract. From the above, it was confirmed that fermenting rice germ can provide a muscle strengthening effect that has never existed before, and it is stronger than protein intake.
Further, as shown in FIG. 6, cell proliferation was significantly increased by adding Compound 1 at a concentration of 3 to 30 μg / mL. In addition, the fermented rice germ extract (10 μg / mL), which was a positive control, also increased significantly. From the above, it was suggested that the fermented rice germ extract and its component Compound 1 have the activity of promoting the proliferation of myocytes. From the above, it was confirmed that the fermented rice germ extract and its component Compound 1 are useful as a muscle mass increasing agent.

Test Example 3: Muscle hypertrophy promoting factor IGF-1 expression promoting activity A component (Compound 1-5) isolated from a rice germ fermentation extract was added to mouse myoblast C2C12 at a concentration of 1 and 10 μg / mL, and Differentiation induction was performed at the same time. After culturing for 1 week, the cells were collected, and the mRNA expression level of the muscle growth factor IGF-1 was quantitatively analyzed. At that time, GAPDH was used as an endogenous control for correction. The result is shown in FIG.

Effect of Example in Test Example 3 As shown in FIG. 7, expression was promoted by adding Compound 1 (1 μg / mL) and Compound 5 (1 μg / mL) in IGF-1, which is a muscle weight gain factor. From the above, it was confirmed that Compound 1 and 5 are useful as muscle weight gain gene expression promoters.

Test Example 4: Muscle contraction promoting action For mouse myoblast C2C12 embedded in collagen gel, fermented rice germ extract (10 μg / ml) and Compound 5 (10 μg / ml), insulin-like growth factor 1 (IGF-1, 1 ng / ml) was added and differentiation was induced at the same time. After inducing differentiation for 2 weeks, the size of the collagen gel was measured and the effect on the contractile force was evaluated. The result is shown in FIG.

The collagen gel contraction test was conducted as an index of the effect muscle contraction of the example in Test Example 4. As a result, as shown in FIG. 8, similar to the positive control IGF-1, the addition of the rice germ ferment extract and Compound 5 resulted in significant contraction of the collagen gel. From the above, it was confirmed that Compound 5 is useful as an agent for improving muscle contraction force.

Based on the above effects, it was confirmed that the fermented rice germ extract and Compound 1-5 obtained thereby were useful as muscle enhancers.

Although the compounding example of the muscle strengthening agent of this invention is shown below, 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
Muscle enhancer 0.5
100.0 wt%

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
Muscle enhancer 1.0
100.0 wt%

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
Muscle enhancer 0.4
100.0 wt%

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
Muscle enhancer 0.4
Perfume
Water residue
100.0 wt%

Formulation Example 5: Soft drink (functional display food or food for specified health use)
Fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
Muscle enhancer 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
Muscle enhancer 1.0
100.0 wt%

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
Muscle enhancer 1.0
100.0 wt%

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

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

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
Muscle enhancer 1.0
Taurine 0.1
Vitamins 0.5
Minerals 0.5
100.0 wt%

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

As described above, the present invention can provide a novel muscle-enhancing agent.

Claims (13)

A muscle differentiation induction promoter comprising a fermented extract obtained by fermenting rice bran and / or rice germ to obtain a fermented product, and then extracting the fermented rice product with a polar solvent. A muscle differentiation-inducing promoter comprising a distribution obtained by distributing the fermentation extract according to claim 1 with a polar solvent as an active ingredient. A muscle differentiation induction promoter comprising as an active ingredient at least one compound selected from stigmasterol, ergosterol peroxide, β-sitosterol glucoside, and glucosylceramide. A muscle enhancer comprising as an active ingredient a fermented extract obtained by fermenting rice bran and / or rice germ to obtain a fermented product, and then extracting the fermented rice product with a polar solvent. The muscle bulking agent which uses the distribution which distributed the said fermentation extract described in Claim 4 with the polar solvent as an active ingredient. A muscle bulking agent containing stigmasterol as an active ingredient. A muscle weight gain gene expression promoter comprising a fermented extract obtained by fermenting rice bran and / or rice germ to obtain a fermented product, and then extracting the fermented rice product with a polar solvent. A muscle weight gain gene expression promoter comprising as an active ingredient a distribution obtained by distributing the fermentation extract according to claim 7 with a polar solvent. A muscle weight gain gene expression promoter comprising at least one of stigmasterol and glucosylceramide as an active ingredient. A muscle contraction improving agent comprising a fermented extract obtained by fermenting rice bran and / or rice germ to obtain a fermented product and then extracting the fermented rice product with a polar solvent as an active ingredient. The muscle contraction power improvement agent which uses the distribution which distributed the said fermentation extract described in Claim 10 with the polar solvent as an active ingredient. A muscle contraction force improver containing glucosylceramide as an active ingredient. The muscle strengthening agent which uses the agent of any one of Claims 1-12 as an active ingredient.