JP7246965B2 - Sarcopenia obesity preventive/improving agent - Google Patents

Description

Application of Article 30, Paragraph 2 of the Patent Act Presented at the 23rd European Society of Sports Sciences Congress (Dublin Convention Center, Ireland) on July 5, 2018

TECHNICAL FIELD The present invention relates to a novel agent for preventing/ameliorating sarcopenic obesity. INDUSTRIAL APPLICABILITY The present invention is widely used in pharmaceuticals, foods, external preparations for skin, and the like.

Age-related loss of skeletal muscle mass and muscle strength (sarcopenia) reduces resting energy expenditure (directly) and physical activity (indirectly). As a result, it induces an increase in body fat (obesity), resulting in increased insulin resistance and tumor necrosis factor. These further promote sarcopenia and bring about a negative link between sarcopenia and obesity. In addition, ``sarcopenic obesity'', which is a combination of sarcopenia and obesity, further increases the risk of lifestyle-related diseases (Kim et al., 2009). Therefore, it is necessary to break the negative chain between obesity and muscle atrophy in sarcopenic obesity by promoting lipolysis/burning and maintaining muscle mass.
In previous studies, ingestion of fucoxanthin in experimental animals suppressed the weight gain of white adipose tissue (Maeda et al., 2007; Maeda et al., 2009), and the metabolites of fucoxanthin A certain fucoxanthinol has been reported to suppress the growth and maturation of adipocytes (Maeda et al., 2006). However, although decomposing and shrinking hypertrophied adipocytes is also important for anti-obesity, there are few examples of verifying the effectiveness of fucoxanthin from this point of view.
On the other hand, although the effect of fucoxanthin on muscle atrophy has not been clarified, it has been confirmed that administration of β-carotene to mice suppressed muscle atrophy caused by reactive oxygen species (Ogawa et al., 2013). ).
However, it is not known that fucoxanthin and fucoxanthinol have both obesity prevention effect (visceral fat reduction) and muscle atrophy suppression effect.

Under the above background, the present inventors have found that fucoxanthin, which is one of the carotenoids abundantly contained in seaweed, and fucoxanthinol, which is a metabolite thereof, have an obesity prevention effect (visceral fat reduction effect, fat decomposition in mature adipocytes). It was found in cell/animal experiments that both a stimulating effect and an inhibitory effect on muscle atrophy were obtained, and the present invention was completed.
That is, an object of the present invention is to provide an agent for preventing and improving sarcopenia obesity, which contains, as an active ingredient, a novel ingredient having both an obesity prevention effect and a muscle atrophy inhibition effect.

The technical features of the present invention for solving the above problems are as follows.
1. An agent for preventing and improving sarcopenia obesity containing at least one of fucoxanthin and fucoxanthinol as an active ingredient.
2. A lipolytic activity enhancer in mature adipocytes containing at least one of fucoxanthin and fucoxanthinol as an active ingredient.
3. A visceral fat reducing agent containing at least one of fucoxanthin and fucoxanthinol as an active ingredient.
4. A muscle atrophy inhibitor in skeletal muscle cells containing at least one of fucoxanthin and fucoxanthinol as an active ingredient.
5. An agent for preventing and improving sarcopenia obesity containing at least one of fucoxanthin and fucoxanthinol as an active ingredient, wherein the agent for preventing and improving sarcopenia obesity enhances lipolytic activity in mature adipocytes and An agent for preventing and improving sarcopenic obesity characterized by preventing and improving sarcopenic obesity by suppressing muscle atrophy.
6. An agent for preventing and improving sarcopenia obesity containing at least one of fucoxanthin and fucoxanthinol as an active ingredient, wherein the agent for preventing and improving sarcopenia obesity reduces visceral fat and suppresses muscle atrophy in skeletal muscle cells. An agent for preventing and improving sarcopenic obesity characterized by preventing and improving sarcopenic obesity.

1 is a graph showing the evaluation of lipolysis promoting action of fucoxanthinol. 1 is a graph and photographs showing evaluation results of fucoxanthinol myotube protective action. FIG. 2 shows a protocol for evaluating the muscle atrophy-inhibiting action and visceral fat-reducing action of fucoxanthin in muscle atrophy-induced model mice. Fig. 4 is a graph showing the evaluation results of the muscle atrophy-suppressing effect and visceral fat-reducing effect of fucoxanthin in muscle atrophy-induced model mice.

The present invention will be described in detail below.
The present invention is characterized by using at least one of fucoxanthin and fucoxanthinol as an active ingredient.

Although the method for obtaining the fucoxanthin is not particularly limited, it is preferably extracted from natural products. This is because more stable fucoxanthin can be obtained.
In addition, when obtaining fucoxanthin from natural products, the raw materials are not particularly limited, and examples thereof include seaweeds, brown algae, and microalgae. Either one of these may be used, or both of them may be used. Among these, it is particularly preferable to extract from microalgae.

The above "seaweed" is not particularly limited, but it is preferable to use, for example, kelp, wakame seaweed, arame, sargassum, red mokumoku, hijiki, and the like. This is because they contain a relatively large amount of fucoxanthin, are abundant as resources, and are industrially useful as raw materials. Incidentally, these may be used alone, or two or more of them may be used in combination.
Examples of the above-mentioned "brown algae" include, for example, Laminariales such as Laminariaceae and Chordaceae; Fucales such as Fucaceae and Sargassaceae; Brown algae belonging to the order Chordariales such as Chordaceae and Spermatochnaceae are more preferred, but not limited thereto. Incidentally, these may be used alone, or two or more of them may be used in combination.
Although the above-mentioned "microalgae" is not particularly limited, it is preferable to use, for example, Phaeodactylum tricornutum. This is because a higher concentration of fucoxanthin can be obtained.

For the seaweeds, brown algae, and microalgae, one of the extracts may be used, or two or more extracts may be used in combination.

Although the extraction method for obtaining fucoxanthin from the seaweeds, brown algae, and microalgae is not particularly limited, examples thereof include polar solvent extraction and supercritical extraction. Only one of these may be performed, or both of them may be performed. Moreover, this extraction may be performed only once for each method, or may be performed twice or more.

Here, when extracting by polar solvent extraction, the polar solvent used is not particularly limited, but examples include water, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, acetic acid, Examples include ethyl acetate, ether, hexane, and the like. Among these, water, methanol and ethanol are preferred. This is because the active ingredient can be efficiently extracted. Incidentally, these may be used alone or in combination of two or more.

When water is used as the extraction solvent, the extraction temperature is 20 to 100°C, preferably 40 to 70°C. This is because if the extraction temperature is too low, it is difficult to extract the active ingredient. The type of water for extraction is not particularly limited, and tap water, distilled water, mineral water, alkaline ion water, etc. can be used.

When ethanol or water-containing ethanol is used as the extraction solvent, the ethanol concentration is preferably 30 wt % or more, preferably 50 wt % or more (including 100 wt %). This is because if the amount is less than 30 wt%, the extraction amount of the active ingredient tends to decrease. The extraction temperature should be 0 to 95°C, preferably 20 to 80°C. It should be noted that the aqueous ethanol extraction may be repeated at various concentrations in order to improve the content of the active ingredient.

In the case of extraction with a polar solvent, the extraction method is not particularly limited. can be used. In addition, when performing extraction by the method mentioned above, you may perform only one of these methods, and you may combine these methods. Moreover, these extractions may be performed only once, or may be performed twice or more.

As a specific method, the raw material for extraction is put into a treatment tank filled with an extraction solvent, and the active ingredient is eluted while stirring. For example, when water, hydrous ethanol, or ethanol is used as the extraction solvent, the polar solvent is used in an amount (weight ratio) of about 5 to 100 times that of the raw material for extraction, and the extraction is performed for about 1 minute to 150 hours. After eluting the active ingredient in the solvent, an extract is obtained by filtering to remove the extraction residue. After that, the extract is diluted, concentrated, dried, purified, etc. according to a conventional method to obtain an extract containing a high concentration of fucoxanthin.
Examples of purification methods include activated carbon treatment, resin adsorption treatment, ion exchange resin, liquid-liquid countercurrent distribution, and the like.

Furthermore, when performing extraction by supercritical extraction, the supercritical fluid used at this time is not particularly limited, but examples thereof include carbon dioxide and nitrogen. In addition, these may use only 1 type, and may use 2 or more types together. Carbon dioxide is particularly preferred among these. This is because the active ingredient can be extracted more easily. Moreover, the extraction method at this time may be performed by a known method. After that, the extract is diluted, concentrated, dried, purified, etc. according to a conventional method to obtain an extract containing a high concentration of fucoxanthin.

Commercially available fucoxanthins can be used, for example, fucoxanthin-1, fucoxanthin-5, fucoxanthin-P1, fucoxanthin-WSP0.1, fucoxanthin-WSP0. 1, Fucolex (registered trademark)-5, Fucolex (registered trademark)-1, and the like can be used.

The method for obtaining fucoxanthinol is not particularly limited, and it can be obtained, for example, by a known method such as JP-A-2009-033970.

In addition, the above fucoxanthinol can be a commercially available product, for example, fucoxanthinol manufactured by Wako Pure Chemical Industries, Ltd. can be used.

The agent for preventing and improving sarcopenia obesity of the present invention can be used as a material for various foods and drinks. Examples of food and drink include edible oil (salad oil, confectionery (gum, candy, caramel, chocolate, cookies, snacks, jelly, gummies, tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk , ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, black tea, tea, carbonated drinks, sports drinks, etc.), general foods such as health foods (tablets, Capsules, etc.), nutritional supplements (energy drinks, etc.), and the sarcopenia obesity prevention/amelioration agent of the present invention may be appropriately added to these foods and drinks.

Various ingredients can be blended into these foods and drinks depending on their type, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, and succinate. 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, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, pigments, flavors, and preservatives can be used. Furthermore, this sarcopenia obesity prevention and improvement agent with a health maintenance function includes other antioxidants and health food materials, such as reduced ascorbic acid (vitamin C), vitamin E, reduced glutatin, tocotrienol, vitamin A. Derivatives, lycopene, β-cryptoxanthin, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sesamin, lignans, catechins, isoflavones, chalcones, tannins, flavonoids, coumarin, isocoumarin blueberry extract, health food material) V. (vitamin) A, V. B1, V. B2, V. B6, V. B12, V. C, V. D, V. E, V. P, choline, niacin, pantothenic acid, calcium folate, EPA, oligosaccharide, dietary fiber, squalene, soy lecithin, taurine, donaliella, protein, octacosanol, DHA, egg yolk lecithin, linoleic acid, lactoferrin, magnesium, zinc, chromium, selenium , potassium, heme iron, oyster meat extract, chitosan, chitin oligosaccharide, collagen, chondroitin, elastin, turmeric, licorice, lycium, cinnamon bark, hawthorn, ginger, reishi mushroom, clam extract, soft-shelled turtle, licorice, wolfberry, cinnamon bark, seiyou, Hawthorn, Ginger, Ganoderma Lucidum, Plantain, Chamomile, Chamomile, Dandelion, Hibiscus, Honey, Bohlen, Royal Jelly, Lime, Lavender, Rosehip, Rosemary, Sage, Bifidobacterium, Faecalis, Lacris, Wheat Germ Oil, Sesame Oil, Perilla Oil, soybean oil, medium-chain fatty acids, agaricus, ginkgo biloba extract, chondroitin, brown rice germ extract, litchi, onion, DHA, EPA, DPA, sweet tea, cordyceps, garlic, bee larvae, papaya, pu-erh, propolis, megusuri tree , Herb mushroom, royal jelly, saw palmetto, hyaluronic acid, gaba, harp seal oil, shark cartilage, glucosamine, lecithin, phosphatidylserine, ginseng, mulberry leaf, soybean extract, echinacea, eleuthero, barley extract, olive leaf, olive Berries, 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, marian thistle, bay, sage, rosemary, lafuma, Black vinegar, bitter gourd, maca, safflower, flax, oolong tea, flower thorns, caffeine, capsaicin, xylooligosaccharide, glucosamine, buckwheat, citrus, dietary fiber, protein, prunes, spirulina, barley grass, nucleic acids, yeast, shiitake mushrooms, plum meat , amino acid, deep sea shark extract, noni, oyster meat, soft-shelled turtle, champignon, plantain, acerola, pineapple, banana, peach, apricot, melon, strawberry, raspberry, orange, fucoidan, meshimakobu, cranberry, zinc, iron, silk peptide, Glycine, Niacin, Chaste Tree, Ceramide, L-Cysteine, Red Wine Juice, Millet, Horsetail, Biotin, Centella Asiatica, Haskap, Pycnogenol, Butterbur, Rhubar Beer, clove, puerh, citric acid, brewer's yeast, melilot, black ginger, ginger, zedoary, nattokinase, red rice koji, tocotrienol, lactoferrin, tartary buckwheat, cocoa, dokudami, kiwi, hihatsu, lotus leaf, paffia, star fruit, etc. can be compounded.

As a specific production method, fucoxanthin and/or fucoxanthinol are spray-dried or freeze-dried together with powdered cellulose, and this is easily converted into powder, granules, tablets, or a solution for food and drink (instant foods, etc.). can be contained in
In addition, fucoxanthin and/or fucoxanthinol can be dissolved in, for example, fat, ethanol, glycerin, or a mixture thereof to form a liquid, which can be added to beverages or solid foods. If necessary, it can be mixed with a binder such as gum arabic or dextrin to form powder or granules, which can be added to beverages or solid foods.

When the agent for preventing and improving sarcopenia obesity of the present invention is applied to food and drink, the amount of the active ingredient to be added is 1 to 20 wt% or less in total in food and drink, since the main purpose is disease prevention and health maintenance. is preferred.

The agent for preventing and improving sarcopenia obesity of the present invention may be used as a material for drugs (including pharmaceuticals and quasi-drugs). The agent for preventing and improving sarcopenia obesity of the present invention can be appropriately blended with raw materials for drug formulations. Pharmaceutical raw materials that can be blended in the agent for preventing and improving sarcopenia obesity of the present invention include, for example, excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cacao butter, hydrogenated vegetable oil, kaolin, talc, etc.), binders (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrants (sodium alginate, agar, carbonate) Sodium hydride, calcium carbonate, sodium lauryl sulfate, monoglyceride stearate, starch, lactose, gum arabic powder, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cacao butter, hydrogenated oil, etc.), absorption enhancers (No. quaternary ammonium base, sodium lauryl sulfate, etc.), adsorbents (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearate, polyethylene glycol, etc.), and the like.

The method of administration of the agent for preventing and improving sarcopenia obesity according to the present invention can generally be oral administration in the form of tablets, pills, soft/hard capsules, fine granules, powders, granules, liquids, and the like. , parenteral administration. When administered as a parenteral drug, it is applied in the form of a solution, or in the form of a poultice, lotion, ointment, tincture, cream, etc., with the addition of a dispersant, suspending agent, stabilizer, etc. can do.

The dosage may vary depending on the administration method, disease state, age of the patient, etc., but for adults, 1 to 1000 mg of the active ingredient can be administered per day, and for children, 0.5 to 500 mg per day.
The compounding ratio of the agent for preventing and improving sarcopenia obesity can be appropriately changed depending on the dosage form. should be about 0.01 to 10 wt %. Since the dose varies depending on various conditions, there are cases where a dose smaller than the above dose is sufficient, and there are cases where it is necessary to administer a dose exceeding the above range.

Forms of external skin materials to which the agent for preventing and improving sarcopenia obesity of the present invention can be incorporated include, for example, milky lotions, soaps, facial cleansers, bath agents, creams, milky lotions, lotions, eau de colognes, shaving creams, and shaving lotions. , cosmetic oil, suntan/sunscreen lotion, face powder, foundation, perfume, mask, nail cream, enamel, enamel remover, eyebrow, blusher, eye cream, eye shadow, mascara, eyeliner, lipstick, lip balm, shampoo, Examples include rinses, treatments, hair dyes, dispersions, cleansers and the like.
Forms of drugs or quasi-drugs in which the agent for preventing and improving sarcopenia obesity of the present invention can be incorporated include ointments, creams, liquids for external use, and the like.

In addition to the agent for preventing and improving sarcopenia obesity according to the present invention, the external preparation for skin in the above form includes ingredients and oils that are blended in external preparations for skin such as cosmetics and quasi-drugs to the extent that the effect of preventing and improving sarcopenia obesity is not impaired. , higher alcohols, fatty acids, ultraviolet absorbers, powders, pigments, surfactants, polyhydric alcohols/sugars, polymers, physiologically active ingredients, solvents, antioxidants, perfumes, preservatives and the like can be added.
Examples are listed below, but the invention is not limited to these examples.
(1) Examples of oil components Ester oil phase components: glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isostearic acid isocetyl, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, adipine diisopropyl acid, isoarachyl neopentanoate, tri(caprylic-capric acid) glyceryl, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentaerythritol tetra-2-ethylhexanoate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isostearyl laurate, isotridecyl myristate, isocetyl myristate, isostearyl myristate, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctoate, ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di(caprylic-capric acid), propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, Glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, poly Glycerin oleate, polyglycerin isostearate, charcoal Dipropyl acid, dialkyl carbonate (C12-18), triisocetyl citrate, triisoaralkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyltriethyl citrate, citric acid Acetyl tributyl acid, trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, hydroxystearin cholesteryl acid, cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, isocetyl 12-stearoylhydroxystearate, stearyl 12-stearoylhydroxystearate, isostearyl 12-stearoylhydroxystearate and the like.
Hydrocarbon-based oil phase components: squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, vaseline and the like.
Animal and vegetable oils and their hydrogenated oils, and naturally derived waxes: Animal oils such as beef tallow, hydrogenated beef tallow, lard, hydrogenated lard, horse oil, hydrogenated horse oil, mink oil, orange roughy oil, fish oil, hydrogenated fish oil, egg yolk oil, etc. Its hydrogenated oil, avocado oil, almond oil, olive oil, cocoa butter, apricot kernel oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil, perilla oil, Tea seed oil, camellia oil, corn oil, rapeseed oil, hydrogenated rapeseed oil, palm kernel oil, hydrogenated palm kernel oil, palm oil, hydrogenated palm oil, peanut oil, hydrogenated peanut oil, castor oil, hydrogenated castor oil, sunflower oil, Grape seed oil, jojoba oil, hydrogenated jojoba oil, macadamia nut oil, medhome oil, cottonseed oil, hydrogenated cottonseed oil, coconut oil, vegetable oils such as hydrogenated coconut oil and their hydrogenated oils, beeswax, high acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin , liquid lanolin, carnauba wax, montan wax, and the like.
Silicone-based oil phase components: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethyl Siloxane-methylcetyloxysiloxane copolymer, dimethylsiloxane-methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic Examples include silicone, trimethylsiloxysilicate, silicone RTV rubber, and the like.
Fluorinated oil phase components: perfluoropolyether, fluorine-modified organopolysiloxane, pitch fluoride, fluorocarbon, fluoroalcohol, fluoroalkyl/polyoxyalkylene co-modified organopolysiloxane, and the like.
(2) Examples of higher alcohols include lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol and octyldodecanol.
(3) Examples of fatty acids Caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid , erucic acid, 2-ethylhexanoic acid and the like.
(4) Examples of UV absorbers Para-aminobenzoic acid, amyl para-aminobenzoate, ethyl dihydroxypropyl para-aminobenzoate, glyceryl para-aminobenzoate, ethyl para-aminobenzoate, octyl para-aminobenzoate, octyldimethyl para-aminobenzoate, ethylene glycol salicylate, salicylic acid Octyl, triethanolamine salicylate, phenyl salicylate, butyl phenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl p-methoxycinnamate, 2-ethylhexyl p-methoxycinnamate, mono-2-di-p-methoxycinnamate Glyceryl ethylhexanoate, isopropyl paramethoxycinnamate, diethanolamine paramethoxyhydrocinnamate, diisopropyl-diisopropylcinnamate mixture, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salt, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, butylmethoxydibenzoylmethane, 2,4,6-trianilino-p-(carbo-2- ethylhexyl-1-oxy)-1,3,5-triazine, 2-(2-hydroxy-5-methylphenyl)benzotriazole, methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenyl acrylates, phenylbenzimidazole sulfate, 3-(4-methylbenzylidene)camphor, isopropyldibenzoylmethane, 4-(3,4-dimethoxyphenylmethylene)-2,5-dioxo-1-imidazolidine propionate 2-ethylhexyl, etc. , and polymer derivatives and silane derivatives thereof.
(5) Examples of powders and pigments Pigments such as Red No. 104, Red No. 201, Yellow No. 4, Blue No. 1, Black No. 401, lake pigments such as Yellow No. 4 AL lake and Yellow No. 203 BA lake, nylon powder , silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polymers such as polyethylene powder, yellow iron oxide, red iron oxide, black Colored pigments such as iron oxide, chromium oxide, carbon black, ultramarine blue, and Prussian blue, white pigments such as zinc oxide, titanium oxide, and cerium oxide, extender pigments such as talc, mica, sericite, kaolin, plate-like barium sulfate, and titanium mica Pearl pigments such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, metal salts such as magnesium silicate, inorganic powders such as silica and alumina, aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, myristine metal soaps such as magnesium oxide, zinc laurate, and zinc undecylenate; bentonite, smectite, boron nitride; The shape (spherical, rod-like, needle-like, plate-like, amorphous, scaly, spindle-like, etc.) and particle size of these powders are not particularly limited. These powders may be subjected to conventional surface treatments such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil treatment, N-acylated lysine treatment, The surface may or may not have been previously surface-treated by polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment, or the like.
(6) Examples of surfactants Anionic surfactants: fatty acid soap, α-acylsulfonate, alkylsulfonate, alkylarylsulfonate, alkylnaphthalenesulfonate, alkylsulfate, POE alkyl ether sulfate salts, alkylamide sulfates, alkyl phosphates, POE alkyl phosphates, alkylamide phosphates, alkyloyl alkyl taurate salts, N-acyl amino acid salts, POE alkyl ether carboxylates, alkyl sulfosuccinates, alkyl sulfo Examples include sodium acetate, acylated hydrolyzed collagen peptide salts, perfluoroalkyl phosphate esters, and the like.
Cationic surfactants: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride , amidopropyldimethylhydroxypropylammonium chloride, diethylaminoethylamide stearate, dimethylaminopropylamide stearate, lanolin derivative quaternary ammonium salts, and the like.
Amphoteric surfactants: carboxybetaine type, amidobetaine type, sulfobetaine type, hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine type, aminocarboxylate type, imitazoline derivative type, amidoamine type and the like.
Nonionic surfactant: propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE sorbit fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hardened castor oils, POE castor oil, POE/POP copolymers, POE/POP alkyl ethers, polyether-modified silicone lauric acid alkanolamides, alkylamine oxides, hydrogenated soybean phospholipids, and the like.
Natural surfactants: lecithin, saponin, sugar surfactants and the like.
(7) Examples of polyhydric alcohols and sugars Ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1, 3 -Butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, pullulan and the like. In addition, chemically modified products thereof can also be used.
(8) Examples of polymers Acrylic ester/methacrylic ester copolymer (Plussize, manufactured by GOO Chemical Co., Ltd.), vinyl acetate/crotonic acid copolymer (Resin 28-1310, manufactured by NSC), vinyl acetate/croton Acid/vinyl neodecanate copolymer (28-2930, manufactured by NSC), methyl vinyl ether maleic acid half ester (Gantrez ES, manufactured by ISP), T-butyl acrylate/ethyl acrylate/methacrylic acid copolymer (Rubimer , manufactured by BASF), vinylpyrrolidone/vinyl acetate/vinyl propionate copolymer (Lubiscol VAP, manufactured by BASF), vinyl acetate/crotonic acid copolymer (Lubiset CA, manufactured by BASF), vinyl acetate/croton Acid/vinylpyrrolidone copolymer (Lubiset CAP, manufactured by BASF), vinylpyrrolidone/acrylate copolymer (Lubiflex, manufactured by BASF), acrylate/acrylamide copolymer (Ultrahold, manufactured by BASF), vinyl acetate/ butyl maleate/isobornyl acrylate copolymer (Advantage, manufactured by ISP), carboxyvinyl polymer (Carbopol, manufactured by BFGoodrich), acrylic acid-alkyl methacrylate copolymer (Pemulen, manufactured by BFGoodrich), etc. Anionic polymer compounds, acetic acid amphoterates of dialkylaminoethyl methacrylate polymers (Yukaformer, manufactured by Mitsubishi Chemical Corporation), octylacrylamide acrylate/hydroxypropyl acrylate/butylaminoethyl methacrylate copolymers (AMPHOMER, manufactured by NSC) ), vinylpyrrolidone/dimethylaminoethyl methacrylate quaternary (GAFQUAT, manufactured by ISP), and methylvinylimidazolium chloride/vinylpyrrolidone copolymer (Rubicoat, manufactured by BASF). Molecular compound, polyvinylpyrrolidone (Lubiskol K, manufactured by BASF), vinylpyrrolidone/vinyl acetate copolymer (Lubiskol VA, manufactured by BASF), vinylpyrrolidone/dimethylaminoethyl methacrylate copolymer (copolymer 937, manufactured by ISP ), nonionic polymer compounds such as vinylcaprolactam/vinylpyrrolidone/dimethylaminoethyl methacrylate copolymer (copolymer VC713, manufactured by ISP). Also, cellulose or its derivatives, keratin and collagen or its derivatives, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharide, xanthan gum, carrageenan, high-methoxyl pectin, low-methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabino Naturally derived high molecular compounds such as galactan, karaya gum, tragacanth gum, alginic acid, albumin, casein, curdlan, gellan gum and dextran can also be suitably used.
(9) Examples of physiologically active ingredients Examples of physiologically active ingredients include substances that impart some physiological activity to the skin when applied to the skin. For example, whitening ingredients, anti-inflammatory agents, anti-aging agents, UV protection agents, slimming agents, tightening agents, antioxidants, hair growth agents, hair restorers, moisturizers, blood circulation promoters, antibacterial agents, bactericides, desiccants, Cooling agents, warming agents, vitamins, amino acids, wound healing accelerators, irritation reducing agents, analgesics, cell activators, enzyme components, and the like. Examples of these suitable ingredients include Angelica keiskei koidzha extract, avocado extract, amacha extract, althea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract, ageitsu Extract, Echinashi leaf extract, Scutellaria root extract, Phellodendron bark extract, Coptis extract, Barley extract, Hypericum extract, Dead nettle extract, Dutch mustard extract, Orange extract, Seawater dried matter, Seaweed extract, Hydrolyzed elastin, Hydrolyzed wheat powder, Hydrolyzed silk , Chamomile extract, Carrot extract, Kawara mugwort extract, Licorice extract, Karkade extract, Persimmon extract, Kiwi extract, Cinchona extract, Cucumber extract, Guanosine, Gardenia extract, Kumazasa extract, Clara extract, Walnut extract, Grapefruit extract, Clematis extract, Chlorella extract , mulberry extract, gentian extract, black tea extract, yeast extract, burdock extract, fermented rice bran extract, rice germ oil, comfrey extract, collagen, cowberry extract, rhinoceros extract, rhinoceros extract, rhinoceros extract, salvia extract, soapwort extract, bamboo extract , hawthorn extract, Japanese pepper extract, shiitake extract, rhubarb extract, lichen extract, perilla extract, linden extract, meadowsweet extract, peony extract, calamus root extract, white birch extract, horsetail extract, ivy extract, hawthorn extract, sambucus extract, yarrow extract extract, peppermint extract, sage extract, mallow extract, cnidium extract, juniper extract, soybean extract, turmeric extract, thyme extract, tea extract, clove extract, cinnamon extract, chimp extract, angelica root extract, calendula officinalis extract, tonin extract, spruce extract, Houttuynia cordata Extract, Tomato Extract, Natto Extract, Carrot Extract, Garlic Extract, Novara Extract, Hibiscus Extract, Bakumondou Extract, Parsley Extract, Honey, Hamamelis Extract, Parietalia Extract, Bisabolol Extract, Bisabolol, Loquat Extract, Coltsfoot Extract, Butterbur Extract, Bukuryo extract, butcher bloom extract, grape extract, propolis, loofah extract, safflower extract, peppermint extract, bodaiju extract, button extract, hop extract, pine extract, horse chestnut extract skunk cabbage extract, soapberry extract, melissa extract, peach extract, cornflower extract, eucalyptus extract, saxifrage extract, yokuinin extract, mugwort extract, lavender extract, apple extract, lettuce extract, lemon extract, astragalus extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract, strawberry extract, hihatsu extract, lotus leaf extract, paffia extract, star fruit extract and the like can be mentioned.
In addition, deoxyribonucleic acid, mucopolysaccharides, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, biopolymers such as hydrolyzed eggshell membranes, amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidone carboxylate , betaine, whey, moisturizing ingredients such as trimethylglycine, sphingolipids, ceramides, phytosphingosine, cholesterol, cholesterol derivatives, oily ingredients such as phospholipids, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, Anti-inflammatory agents such as hydrocoltisone, vitamins such as vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin C ester, allantoin, diisopropylamine dichloro active ingredients such as acetate and 4-aminomethylcyclohexanecarboxylic acid; antioxidants such as tocopherols, carotenoids, flavonoids, tannins, lignans and saponins; cell activators such as α-hydroxy acids and β-hydroxy acids; Blood circulation promoters such as vitamin E derivatives, retinol, wound healing agents such as retinol derivatives, arbutin, kojic acid, placenta extract, whitening agents such as sulfur, ellagic acid, linoleic acid, tranexamic acid, glutathione, cepharanthine, licorice extract, Capsicum tincture, hinokitiol, garlic iodide extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivatives, calcium pantothenate, D-pantothenyl alcohol, acetylpantothenyl ethyl ether, biotin , allantoin, isopropylmethylphenol, estradiol, ethinyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonylic acid vanillylamide, nonanoic acid vanillylamide, piroctone olamine, glyceryl pentatecanate, L-menthol, mononitroguaiacol, resorcinol, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female sex hormone, cantharis tincture, cyclosporine, zinc pyrithione, hydrocoltisone, minoxidil, polyoxyethylene sorbitan monostearate, peppermint oil, sasanishi Examples include hair growth agents such as hair extract.
(10) Examples of antioxidants sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolylbiguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxy Plant extracts such as toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoids, flavonoids, tannins, lignans, saponins, apple extracts and clove extracts, which are recognized to have anti-oxidation effects, can be used.
(11) Examples of solvents Purified water, ethanol, lower alcohols, ethers, LPG, fluorocarbons, N-methylpyrrolidone, fluoroalcohols, volatile straight silicones, next generation freon and the like.

Examples: In the following test examples, "Fucolex-5" manufactured by Oryza Yuka Co., Ltd. was used as fucoxanthin.
Fucoxanthinol manufactured by Wako Pure Chemical Industries, Ltd. was used as fucoxanthinol.

Test Example 1: Evaluation of lipolytic activity of fucoxanthinol in mature adipocytes (1) Test method
The mature adipocytes on day 7 after induction of differentiation were divided into a control group to which nothing was added and a group to which fucoxanthinol was added at a concentration of 5 μM, and fucoxanthinol was added for 72 hours. After that, the amount of intracellular triacylglycerol (TG), the amount of glycerol released in the medium and the amount of fatty acid released were measured by biochemical analysis.

(2) Results and Effects of Examples in Test Example 1 As a result of adding fucoxanthinol to mature adipocytes, the release of glycerol and fatty acids, which are indicators of lipolysis, increased significantly (see Fig. 1. A, B). ). Furthermore, the fucoxanthinol-added group showed significantly lower intracellular triglyceride content in a concentration-dependent manner (see Fig. 1.C).
From these results, it was confirmed that the addition of fucoxanthinol to mature adipocytes promotes the decomposition of fat and remarkably suppresses the accumulation of triglycerides.

Test Example 2: Evaluation of muscle atrophy inhibitory effect of fucoxanthinol (1) Test method Mature myotube cells were divided into a control group with no addition and a fucoxanthinol addition group (5 μM) and cultured for 24 hours. did Addition of hydrogen peroxide (1 mM) for 24 hours induced oxidative stress-induced muscle atrophy. The myotube area at that time was analyzed using an immunostaining method.

(2) Results and Effects of Examples in Test Example 2 As a result of adding 5 μM fucoxanthinol to muscle cells that had undergone muscle proteolytic induction (adding 1 mM hydrogen peroxide), myotubes were protected. (See Fig. 2(A)).
Furthermore, the addition of fucoxanthinol significantly suppressed the decrease in myotube area compared to the hydrogen peroxide addition group (see FIG. 2(B)).
These results confirmed that fucoxanthinol alleviates the degree of muscle atrophy caused by oxidative stress.

Test Example 3: Effective reduction of visceral fat and subcutaneous fat by oral administration of fucoxanthin and evaluation of muscle mass maintenance/increase effect (1) Test method Subject: ICR mice (5 weeks old) (1) Control Group (Control group: n = 7) (2) Muscle atrophy induction group (DEX group n = 7) (3) Muscle atrophy induction + fucoxanthin administration group (FX-DEX group n = 8). bottom.
Experimental diet: The experimental diet administration method of Hosokawa et al. (2010) was partially modified. Fucoxanthin oil (“Fucolex-5” manufactured by Oryza Yuka Co., Ltd.) and control oil were mixed in the diet and given ad libitum. For muscle atrophy induction, dexamethasone (10 mg/L) suspended in distilled water was drawn freely (see Figure 3).
Experiment period: Preliminary breeding period was 12 weeks, FX administration was 4 weeks, muscle atrophy induction period was 13 days.
Details of measurement: Body weight, wet weight of tibialis anterior muscle, and visceral fat mass were measured to evaluate the effect on the inhibition of muscle atrophy. The results are shown in FIG.

(2) Results and Effects of Examples in Test Example 3 As shown in FIG. 4, a significant decrease in body weight was observed in the DEX group and the FX-DEX group compared to the control group. On the other hand, the tibialis anterior muscle wet weight was significantly decreased in the DEX group compared to the control group (p<0.01), but no significant difference was observed in the FX-DEX group. This confirmed that fucoxanthin suppresses the decrease in tibialis muscle mass. In addition, the FX-DEX group showed significantly lower visceral fat weight than the control group (p<0.01). This confirmed that fucoxanthin reduces visceral fat. From these results, it was confirmed that administration of FX can reduce visceral fat and suppress the decrease in tibialis anterior muscle wet weight, thus alleviating the degree of DEX-induced muscle atrophy.

Effect of Examples As described above, according to Test Examples 1 and 2, fucoxanthinol promotes the decomposition of fat in mature adipocytes and alleviates the degree of muscle atrophy caused by oxidative stress. Therefore, fucoxanthinol prevents sarcopenic obesity. It was confirmed that it is useful as an improving agent.
Further, Test Example 3 confirmed that fucoxanthin is useful as an agent for preventing and improving sarcopenic obesity because fucoxanthin can reduce visceral fat and suppress the decrease in tibialis anterior muscle wet weight.

1 shows a compounding example of an agent for preventing and improving sarcopenia obesity (fucoxanthin) according to the present invention.
Formulation Example 1: Chewing gum
Sugar 53.0 wt%
gum base 20.0
glucose 10.0
Starch syrup 16.0
Perfume 0.5
Sarcopenia obesity prevention and improvement agent 0.5
100.0 wt%

Formulation Example 2: Gummy
Reduced starch syrup 40.0 wt%
Granulated sugar 20.0
Glucose 20.0
gelatin 4.7
Water 9.68
Yuzu Juice 4.0
Yuzu flavor 0.6
Pigment 0.02
Sarcopenia obesity prevention and improvement agent 1.0
100.0 wt%

Formulation Example 3: Candy
Sugar 50.0 wt%
Starch syrup 33.0
Water 14.4
Organic acid 2.0
Perfume 0.2
Sarcopenia obesity prevention and improvement agent 0.4
100.0 wt%

Formulation Example 4: Yogurt (hard/soft)
Milk 41.5 wt%
Skimmed milk powder 5.8
Sugar 8.0
Agar 0.15
gelatin 0.1
Lactic acid bacteria 0.005
Sarcopenia obesity prevention and improvement agent 0.4
Fragrance trace amount
water residue
100.0 wt%

Formulation Example 5: Soft drink
Fructose glucose liquid sugar 30.0 wt%
emulsifier 0.5
Sarcopenia obesity prevention and improvement agent 0.3
Perfume Appropriate amount
purified water residue
100.0 wt%

Formulation Example 6: Tablet candy
Sugar 76.4 wt%
Glucose 19.0
Sucrose fatty acid ester 0.2
Sarcopenia obesity prevention and improvement agent 0.5
Purified water 3.9
100.0 wt%

Formulation Example 7: Soft capsule
Brown rice germ oil 47.0 wt%
Yuzu seed oil 40.0
Emulsifier 12.0
Sarcopenia obesity prevention and improvement agent 1.0
100.0 wt%

Formulation Example 8: Tablet
Lactose 54.0 wt%
Crystalline cellulose 30.0
Starch hydrolyzate 10.0
Glycerin fatty acid ester 5.0
Sarcopenia obesity prevention and improvement agent 1.0
100.0 wt%

Formulation Example 9: Cosmetic cream squalane 20.0 wt%
Beeswax 5.0
Refined jojoba oil 5.0
Glycerin 5.0
Glycerin monostearate 2.0
Polyoxyethylene (20) sorbitan-
Monostearate 2.0
Sarcopenia obesity prevention and improvement agent 1.0
Preservative Appropriate amount Perfume Appropriate amount
purified water residue
100.0 wt%

Formulation Example 10: Lotion ethanol 5.0 wt%
Glycerin 2.0
1,3-butylene glycol 2.0
Polyethylene oleyl ether 0.5
Sodium citrate 0.1
Citric acid 0.1
PEG-60 hydrogenated castor oil 0.5
Phytosteryl/octyldodecyl lauroyl glutamate
1.5
Sarcopenia obesity prevention and improvement agent 0.1
purified water residue
100.0 wt%

Formulation Example 11: Body gel macadamia nut oil 2.0 wt%
Octyldodecyl myristate 10.0
Methylphenylpolysiloxane 5.0
behenyl alcohol 3.0
Stearic acid 3.0
Batyl alcohol 1.0
Glyceryl monostearate 1.0
Polyoxyethylene sorbitol tetraoleate 2.0
Hydrogenated soybean phospholipid 1.0
Ceramide 0.1
Retinol palmitate 0.1
Antiseptic Appropriate amount Centella asiatica extract 1.0
Sarcopenia obesity prevention and improvement agent 1.0
1,3-butylene glycol 5.0
purified water residue
100.0 wt%

Formulation Example 12: Emulsion squalane 4.0 wt%
Vaseline 2.5
Cetanol 2.0
Glycerin 2.0
Lipophilic glyceryl monostearate 1.0
Stearic acid 1.0
L-arginine 1.0
Sarcopenia obesity prevention and improvement agent 0.5
Potassium hydroxide 0.1
Fragrance trace amount
purified water residue
100.0wt%

Formulation Example 13: Bath agent (liquid)
Propylene glycol 50.0 wt%
Ethanol 20.0
Sodium sulfate 5.0
Sarcopenia obesity prevention and improvement agent 0.5
Lanolin 0.5
Avocado oil 0.5
Dye 1.5
Perfume 22.0
100.0wt%

As described above, the present invention can provide an agent for preventing and improving sarcopenia obesity, which contains, as an active ingredient, a novel ingredient having both an obesity prevention effect and a muscle atrophy inhibition effect.

Claims (3)

A muscle atrophy inhibitor in skeletal muscle cells containing at least one of fucoxanthin and fucoxanthinol as an active ingredient. An agent for preventing and improving sarcopenia obesity containing at least one of fucoxanthin and fucoxanthinol as an active ingredient, wherein the agent for preventing and improving sarcopenia obesity enhances lipolytic activity in mature adipocytes and An agent for preventing and improving sarcopenic obesity characterized by preventing and improving sarcopenic obesity by suppressing muscle atrophy. An agent for preventing and improving sarcopenia obesity containing at least one of fucoxanthin and fucoxanthinol as an active ingredient, wherein the agent for preventing and improving sarcopenia obesity reduces visceral fat and suppresses muscle atrophy in skeletal muscle cells. An agent for preventing and improving sarcopenic obesity characterized by preventing and improving sarcopenic obesity.

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