JP2011068588A - Body weight increase inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a body weight increase inhibitor comprising a new peptide as an effective ingredient. <P>SOLUTION: The body weight increase inhibitor comprises as an effective ingredient a peptide derived from rice. There are also provided a PPARγ (peroxisome proliferator-activator receptor) gene expression inhibitor comprising as an effective ingredient a peptide derived from rice, a GLUT4 (glucose transporter 4) gene expression promoter comprising as an effective ingredient a peptide derived from rice, a CPT1 gene expression promoter comprising as an effective ingredient a peptide derived from rice and a CPT1 gene expression promoter comprising as an effective ingredient a protein derived from rice. The peptide inhibits incorporation of sugar into the body to exhibit also a diabetes-inhibiting action. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

The present invention relates to a weight gain inhibitor having a novel component. The present invention is widely used for foods and drinks, pharmaceuticals and the like.

  In spite of the widely known hazard of obesity, obesity has increased significantly in recent years. It is a well-known fact that obesity, that is, excessive accumulation of adipose tissue, causes various diseases, and it has been proposed to treat obesity as a disease as a treatment target. Examples of diseases that develop as a cause of obesity include low back pain, knee joint pain, and osteoarthritis. These orthopedic diseases can be directly caused by weight gain due to obesity. The excessive accumulation of fat associated with obesity causes diabetes, hyperlipidemia, hypertension, or arteriosclerotic diseases. In particular, it has been clarified that the accumulation of visceral fat is involved in the development of these diseases (Non-patent Document 1).

Here, in order to suppress obesity, the expression of PPARγ (Peroxisome Proliferator Activated Receptor: peroxisome proliferator activated receptor) gene is suppressed, thereby suppressing fat accumulation.

  In addition, with the modernization of society, the number of diabetic patients is increasing rapidly not only in Japan but worldwide. In particular, it is known that obesity and excessive accumulation of fat are involved in the onset of type II diabetes with a large number of patients. As for the treatment of type II diabetes, there are exercise therapy and diet therapy as in obesity, but it is difficult to carry out continuously and pharmaceuticals are used. Insulin therapy is used in patients with severe diabetes. However, insulin therapy is always at risk for the side effects of hypoglycemia. As oral hypoglycemic drugs, thiazolidine drugs or sulfonylurea (SU) drugs are often used. However, thiazolidine drugs have side effects such as liver damage, edema, and heart failure, and SU drugs are feared for side effects that promote obesity, and there is a need for safe anti-diabetic drugs that do not increase weight.

  As for the metabolism of carbohydrates in the body, in muscle and adipose tissue, glucose uptake is carried out via a glucose transporter (GLUT) on the cell membrane, and glucose uptake depends on the amount of glucose transporter. The amount is specified. The main glucose transporter of these tissues is called glucose transporter 4 (GLUT4), but it is usually present inside the cell and moves (translocates) onto the cell membrane by insulin stimulation. It is taken up into the cell through the carrier. In addition, it has been reported that transgenic mice in which GLUT4 is overexpressed even in a small amount are unlikely to become diabetic due to a high fat diet (Ikemoto, S. et al .: Proc. Natl. Acad. Sci. USA, 92: 3086-3089, 1995), a material that promotes the expression of GLUT4 in tissues is considered to be effective for the prevention and cure of diabetes.

The insulin receptor plays a role in transmitting the insulin stimulation to the glucose transporter 4. In other words, the insulin receptor is one of tyrosine kinase-coupled receptors and is a protein in which an α subunit that binds to insulin and a β subunit that penetrates the cell membrane and contains tyrosine kinase in the cytoplasm are linked by disulfide bonds. . The insulin receptor binds to insulin to initiate glucose uptake into cells and signal transduction that initiates glycogen synthesis. Insulin tyrosine kinase is activated by binding to the receptor and is autophosphorylated. Insulin receptor substrate 1 (IRS)
1) binds and this IRS1 is phosphorylated. Phosphorylated IRS1 binds to and activates phosphatidylinositol (PI) -3-kinase (PI-3kinase). The activated PI-3 kinase further activates protein kinase B (PKB) by attracting it to the cell membrane. The activated PKB moves GLUT4 to the cell membrane and takes glucose into the cell. Therefore, a material that promotes the expression of the insulin receptor gene is considered to be effective in the prevention and cure of diabetes.

“Metabolism” (USA), 1987, 36, 54-59

Under such a background, as a result of a test using a high fat diet mouse, the peptide derived from rice has an effect of suppressing weight gain, and further suppresses the intake of sugar into the body, thereby having an effect of suppressing diabetes. The present invention was completed.
That is, an object of the present invention is to provide a weight gain inhibitor containing a novel peptide as an active ingredient.

The features of the present invention for solving the above-described problems are as follows.
1. A weight gain inhibitor comprising a peptide derived from rice as an active ingredient.
2. A PPARγ gene expression inhibitor comprising a rice-derived peptide as an active ingredient.
3. A GLUT4 gene expression inhibitor comprising a rice-derived peptide as an active ingredient.
4). A CPT1 gene expression promoter comprising a rice-derived peptide as an active ingredient.
5). A CPT1 gene expression promoter comprising a protein derived from rice as an active ingredient.

It is a graph which shows the body weight gain inhibitory effect at the time of orally administering the rice origin peptide of a present Example to a high fat diet mouse | mouth. It is a graph which shows the PPAR (gamma) gene expression of an accessory testicle when the rice origin peptide of a present Example is orally administered to a high fat diet mouse | mouth. It is a graph which shows the PPAR (gamma) gene expression effect | action of the perirenal fat at the time of orally administering the rice origin peptide of a present Example to a high fat diet mouse | mouth. It is a graph which shows the GLUT4 gene expression of an accessory testicle when the rice origin peptide of a present Example is orally administered to a high fat diet mouse | mouth. It is a graph which shows GLUT4 gene expression of perirenal fat when the peptide derived from the rice of a present Example is orally administered to a high fat diet mouse | mouth. It is a graph which shows the CPT1 gene expression of the liver at the time of orally administering the rice origin peptide and protein of a present Example to a high fat diet mouse | mouth. It is a graph which shows the CPT1 gene expression of the soleus muscle when the peptide and protein derived from the rice of a present Example are orally administered to a high fat diet mouse | mouth.

  Furthermore, the weight gain inhibitor of the present invention is characterized by containing a peptide derived from rice as an active ingredient. Here, the “rice-derived peptide” is a rice-derived protein extracted from rice by a known method (for example, a method described in JP-A-2003-192695), and the rice-derived protein is proteolytically decomposed. It can be obtained by treating with an enzyme.

  The present invention provides a food containing the weight gain inhibitor. The food product may contain the extract as an active ingredient in an amount of 100 to 3,000 mg, preferably 500 to 1500 mg, for example, for a single adult dose. In the weight gain inhibitor of the present invention, the content of the active ingredient may vary depending on age and the like.

  The weight gain inhibitor of the present invention can be used as a material for various foods and drinks. Examples of the food and drink include edible oil (salad oil), confectionery (gum, candy, caramel, chocolate, cookie, snack, jelly, gummy, tablet confection etc.), noodles (soba, udon, ramen etc.), and dairy products ( Milk, ice cream, yogurt, etc.), boiled simmered (boiled kelp, boiled sea bream, small fish simmered, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, tea, tea, carbonated drinks, sports General foods such as beverages), health foods (tablets, capsules, etc.), and nutritional supplements (nutrient drinks, etc.). It is advisable to appropriately blend the weight gain inhibitor of the present invention in these foods and drinks.

  These foods and drinks can be blended with various ingredients depending on the type, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid. 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, this weight gain inhibitor with health maintenance functions includes other antioxidants and health food ingredients such as antioxidants, reduced ascorbic acid (vitamin C), vitamin E, reduced form Glutatin, tocotrienol, vitamin A derivative, lycopene, β-cryptoxanthin, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sezamin, lignans, catechins, isoflavones, chalcones, tannins, Flavonoids, coumarin, isocoumarins, blueberry extract, arbutin, tannin, anthocyanin, apple polyphenol, grape seed extract, ellagic acid, kojic acid, surge extract health food material, 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, keihi, hawthorn, ginger, ganoderma, swordfish extract, suppon, plantain, chamomile, chamomile, dandelion, hibiscus, honey , Boren, Royal Jelly, Lime, Lavender, Rosehip, Rosemary, Sage, Bifidobacterium, Faecalis, Lacris, Wheat Germ Oil, Sesame Oil, Perilla Oil, Soybean Oil, Medium Chain Fatty Acid, Agaricus, Ginkgo Extract, turmeric, chondroitin, brown rice germ extract, litchi, onion, DHA, EPA, DPA, green tea, cordyceps, garlic, bee, papaya, puer, propolis, megsuri tree, yabushitake, royal jelly, saw palmetto, hyaluronic acid, Collagen, Gabba, Harpseal 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, pearl barley, grape seed, peanut seed coat, bilberry, black cohosh, maria thistle, laurel, sage, rosemary, ruffa, black , Goya, maca, safflower, flax, oolong tea, flower spine, caffeine, capsaicin, xylo-oligosaccharide, glucosamine, buckwheat, citrus, dietary fiber, protein, prune, spirulina, barley young leaves, nucleic acid, yeast, shiitake mushroom, plum meat, amino acid , Deep-sea coral 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, Chest Tree, Ceramide, L-Cysteine, L-Carnitine, Red Wine Leaf, Millet, Horsetail, Biotin, Centella Asiatica, Hascup, Pycnogenol, Fuki, Rhubarb, Clove, Rosemary Kin, Puaru, Citric Acid, Beer Yeast, Merirot, Black Zinger, Ginger, Gajutsu, Nattokinase, 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, GABA, fresh coffee bean extract, Japanese bursa extract, kiwi seed extract, Unshu mandarin orange extract, red ginger extract, astaxanthin, walnut extract, kanka extract, white jellyfish polysaccharide, lingonberry extract, fucoxanthin, resveratrol , Strawberry seed extract) and the like can also be blended.

As a specific production method, the weight gain inhibitor of the present invention is used as it is, and in the case of an extract, it is spray-dried or freeze-dried together with powdered dextrin, and this is easily converted into a powder, granule, tablet or solution. Instant foods). If necessary, it can also be mixed with a binder such as gum arabic to form a powder or granules, and added to a solid food. In the case of an extract, it can also be added to a beverage as it is or after being dispersed and dissolved in water, ethanol, glycerin or a mixture thereof.

The weight gain inhibitor of the present invention may be used as a raw material for medicines (including pharmaceuticals and quasi drugs). It can be produced by appropriately blending the weight gain inhibitor of the present invention with a raw material for a pharmaceutical preparation. In addition, the said chemical | medical agent may be used for a human and may be used for mammals other than a human. Examples of the drug substance that can be blended in the weight gain inhibitor of the present invention include excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cocoa butter, hydrogenated vegetable oil, kaolin, talc, and the like. Etc.), binder (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrant (sodium alginate, agar, hydrogen carbonate) Sodium, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose, gum arabic powder, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cocoa butter, hydrogenated oil, etc.), absorption enhancers (fourth) Grade ammonium base, sodium lauryl sulfate, etc. , Adsorbent (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, and the like) and the like.

The administration method of the weight gain inhibitor according to the present invention can generally be administered orally in the form of tablets, pills, soft / hard capsules, fine granules, powders, granules and the like. The water-soluble preparation can be administered orally as a liquid. Furthermore, parenteral administration may be used. When administered as a parenteral agent, the weight gain inhibitor of the present invention is dispersed in an appropriate solubilizing agent such as ethanol or water, and then a dosage form such as a poultice, lotion, ointment, tincture or cream. Can be applied. In addition, the water-soluble preparation of this weight gain inhibitor is in the form of a poultice, lotion, ointment, tincture, cream, etc., as it is or with a dispersant, suspension, stabilizer, etc. added. Can be applied.

The dose may vary depending on the administration method, medical condition, age of the patient, etc., but for adults, it can be generally administered in an amount of about 5 to 200 mg as an active ingredient per day and usually about 0.5 to 100 mg for children.

The compounding ratio when using the weight gain inhibitor of the present invention as a drug can be appropriately changed depending on the dosage form, but is usually about 0.0001 to 30 wt% when administered orally or by mucosal absorption. In the case of parenteral administration, it may be about 0.0001-30 wt%.
In addition, since the dose varies depending on various conditions, a dose smaller than the above dose may be sufficient, or it may be necessary to administer beyond the range. In addition to the weight gain inhibitor, the pharmaceutical composition may include other known compounds commonly used in the pharmaceutical field, and compounds necessary for molding into a form suitable for oral administration. Examples of such compounds include lactose, starch, hydroxypropyl cellulose, kaolin, talc, calcium carbonate and the like.

Even when the weight-suppressing agent of the present invention is used as a skin external preparation (including cosmetics, pharmaceuticals, and quasi-drugs), a weight-suppressing effect can be expected. In addition, the said skin external preparation may be used for a human and may be used for mammals other than a human.
Examples of the external preparation for skin to which the weight suppressant of the present invention can be formulated include, for example, emulsion, soap, face wash, bath preparation, cream, emulsion, lotion, eau de cologne, shaving cream, shaving lotion, makeup Oil, sunscreen / sunscreen lotion, funny powder, foundation, perfume, pack, nail cream, enamel, enamel remover, eyebrow, blusher, eye cream, eye shadow, mascara, eyeliner, lipstick, lip balm, shampoo, rinse, Examples include hair dyes, dispersions, and cleaning materials.
Examples of the form of a pharmaceutical or quasi-drug that can contain the weight suppressant of the present invention include ointments, creams, and liquids for external use.

In addition to the weight suppressive agent according to the present invention, the external preparation for skin of the above-described form includes ingredients, oils, higher alcohols, and other ingredients blended in skin external preparations such as cosmetics and quasi-drugs as long as the weight-suppressing action is not impaired. Fatty acids, ultraviolet absorbers, powders, pigments, surfactants, polyhydric alcohols / sugars, polymers, physiologically active ingredients, solvents, antioxidants, fragrances, preservatives, and the like can be blended.
Examples are listed below, but the present invention is not limited to these examples.

(1) Examples of oil components Ester-based 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, isoaralkyl neopentanoate, glyceryl tri (capryl / caprate), trimethylolpropane tri-2-ethylhexanoate, trimethylol triisostearate Propane, pentaerythritol tetra-2-ethylhexanoate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isolaurate Stearyl, isotridecyl myristate, isocetyl myristate, isostearyl myristate, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl linoleate, octyldodecyl isoleate, isopropyl isostearate Cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethyleneglycol dioctanoate , Ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di (capryl / capric acid), propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, triisopalmitine Glyceryl acid, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyl decyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleic acid Ester, polyglycerol isostearate, dipropyl carbonate, charcoal Dialkyl (C12-18), triisocetyl citrate, triisoaralkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyl decyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, Trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, olein Cholesteryl acid, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, 12-stearoyl hydroxystearate Cetyl, 12-stearoyl-hydroxystearic acid stearyl 12-stearoyl-hydroxystearic acid isostearate, and the like.
Hydrocarbon oil phase components: squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum and the like.
Animal and vegetable oils and their hydrogenated oils, and naturally occurring waxes: beef tallow, hydrogenated beef tallow, lard, hydrogenated tallow, horse oil, hydrogenated horse oil, mink oil, orange luffy oil, fish oil, hydrogenated fish oil, egg yolk oil and other animal oils and Its hardened oil, avocado oil, almond oil, olive oil, cacao butter, kiwi seed oil, apricot 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 , Vegetable oils such as sunflower oil, grape seed oil, jojoba oil, hardened jojoba oil, macadamia nut oil, medhome oil, cottonseed oil, hardened cottonseed oil, coconut oil, hardened coconut oil and its hardened , Beeswax, high acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax and montan wax.
Silicone 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, trimethylsiloxysilicic acid, and silicone RTV rubber.
Fluorine oil phase components: perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl / polyoxyalkylene co-modified organopolysiloxane, and the like.

(2) Examples of higher alcohols Lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, octyldodecanol and the like can be mentioned.

(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 Paraaminobenzoic acid, amyl paraaminobenzoate, ethyldihydroxypropyl paraaminobenzoate, glyceryl paraaminobenzoate, ethyl paraaminobenzoate, octyl paraaminobenzoate, octyldimethyl paraaminobenzoate, ethylene glycol salicylate, salicylic acid Octyl, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl paramethoxycinnamate, 2-ethylhexyl paramethoxycinnamate, mono-2-diparamethoxycinnamate Glyceryl ethylhexanoate, isopropyl paramethoxycinnamate, diethanolamine salt of paramethoxyhydrocinnamic acid, diisopropyl diisopropylcinnamic acid Stealth mixture, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, 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 acrylate, phenylbenzimidazole sulfate, 3- (4-methylbenzylidene) can Examples include full, isopropyldibenzoylmethane, 4- (3,4-dimethoxyphenylmethylene) -2, 5-dioxo-1-imidazolidinepropionate 2-ethylhexyl, and the like, polymer derivatives, silane derivatives, and the like.

(5) Examples of powders and pigments Red 104, Red 201, Yellow 4, Blue 1, Black 401 and other dyes, Yellow 4 AL lake, Yellow 203 BA lake and other lake dyes, nylon powder , Silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polyethylene powder, yellow iron oxide, red iron oxide, black Colored pigments such as iron oxide, chromium oxide, carbon black, ultramarine and bitumen, white pigments such as zinc oxide, titanium oxide, and cerium oxide, extender pigments such as talc, mica, sericite, kaolin, and plate-like barium sulfate, and mica titanium Pearl pigments such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, metal salts such as magnesium silicate, Inorganic powders such as Rica and Alumina, metal soap such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, zinc undecylenate, bentonite, smectite, boron nitride, etc. It is done. There are no particular restrictions on the shape of these powders (spherical, rod-like, needle-like, plate-like, irregular shape, flake-like, spindle-like, etc.) and particle diameter. These powders are conventionally known surface treatments such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil agent treatment, N-acylated lysine treatment, The surface treatment may or may not be performed in advance 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-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate , Alkylamide sulfate, alkyl phosphate, POE alkyl phosphate, alkylamide phosphate, alkyloylalkyl taurine salt, N-acyl amino acid salt, POE alkyl ether carboxylate, alkyl sulfosuccinate, alkyl sulfoacetic acid Sodium, acylated hydrolyzed collagen peptide salt, perfluoroalkyl phosphate, etc. are mentioned.
Cationic surfactant: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride , Behenic acid amidopropyldimethylhydroxypropylammonium chloride, stearic acid diethylaminoethylamide, stearic acid dimethylaminopropylamide, lanolin derivative quaternary ammonium salts, and the like.
Amphoteric surfactants: carboxybetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type, amide sulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline 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 sorbitol fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE cured castor Oil, POE castor oil, POE / POP copolymer, POE / POP alkyl ether, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, and the like.
Natural surfactant: lecithin, saponin, sugar surfactant 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. These chemically modified compounds can also be used.

(8) Examples of polymers Acrylic ester / methacrylic acid ester copolymer (plus size, manufactured by Kyoyo Chemical), 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 (rubymer) , BASF), vinyl pyrrolidone / vinyl acetate / vinyl propionate copolymer (Rubicol VAP, BASF), vinyl acetate / crotonic acid copolymer (Rubiset CA, BASF), vinyl acetate / croton Acid / vinyl pyrrolidone copolymer (Rubiset CAP, manufactured by BASF), vinyl pyrrolidone / acrylate copolymer (Rubiflex, BA SF), acrylate / acrylamide copolymer (Ultrahold, BASF), vinyl acetate / butyl maleate / isobornyl acrylate copolymer (Advantage, ISP), carboxy vinyl polymer (Carbopol, BF Goodrich), anionic polymer compounds such as acrylic acid / alkyl methacrylate copolymer (Pemulene, BF Goodrich), and acetic acid amphoteric products of dialkylaminoethyl methacrylate polymers (Yukaformer, Mitsubishi Chemical) Amphoteric polymer compounds such as octyl acrylate acrylate / hydroxypropyl acrylate / butylaminoethyl methacrylate copolymer (AMPHOMER, NSC), quaternized vinylpyrrolidone / dimethylaminoethyl methacrylate (GAFQUAT, ISP) , Methyl vinyl imidazolium chloride Cationic polymer compounds such as vinyl / vinylpyrrolidone copolymer (rubicoat, manufactured by BASF), polyvinylpyrrolidone (rubiscol K, manufactured by BASF), vinylpyrrolidone / vinyl acetate copolymer (rubiscol VA, manufactured by BASF) ), Nonionic polymer compounds such as vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer 937, manufactured by ISP), vinylcaprolactam / vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer VC713, manufactured by ISP), etc. There is. Cellulose or derivatives thereof, keratin and collagen or derivatives thereof, 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 polymer compounds such as galactan, gum karaya, gum tragacanth, 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, immunostimulants, anti-aging agents, UV protection agents, slimming agents, tanning agents, antioxidants, hair growth agents, hair restorers, moisturizers, blood circulation promoters, antibacterial agents, bactericides, desiccants, A cooling sensation agent, a warming sensation agent, vitamins, an amino acid, a wound healing promoter, an irritation relaxation agent, an analgesic agent, a cell activator, an enzyme component, etc. are mentioned. Examples of these suitable ingredients include, for example, ashitaba extract, avocado extract, amateur extract, altea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract, age Extract, Echinacea leaf extract, Ogon extract, Oat extract, Oen extract, Barley extract, Hypericum extract, Oyster extract, Dutch mustard extract, Orange extract, Seawater dried product, Seaweed extract, Hydrolyzed elastin, Hydrolyzed wheat powder, Hydrolyzed silk , Chamomile extract, Carrot extract, Kawara mugwort extract, Licorice extract, Calcade extract, Oyster extract, Kina extract, Cucumber extract, Guanosine, Gardenia extract, Kumazasa extract, Clarae Kiss, walnut extract, grapefruit extract, clematis extract, chlorella extract, mulberry extract, gentian extract, tea extract, yeast extract, burdock extract, fermented rice bran extract, rice germ oil, comfrey extract, collagen, bilberry extract, saicin extract, psycho extract Extract Kizuta extract, hawthorn extract, elderberry extract, yarrow extract, mint extract, sage extract, mallow extract, senki Sue extract, assembly extract, soybean extract, tiso extract, thyme extract, tea extract, clove extract, chigaya extract, chimpi extract, touki extract, toshinsen extract, tonin extract, spruce extract, dokudami extract, tomato extract, natto extract, carrot extract, garlic extract, Novara extract, hibiscus extract, bacmond extract, parsley extract, honey, hamamelis extract, parietalia extract, toad extract, bisabolol, loquat extract, dandelion extract, burdock extract, bukuro extract, butcher bloom extract, grape extract, propolis, loofah extract, Safflower extract, peppermint extract, bodaige extract, button extract, hop extract, pine extract, marronnier extract, mizubasho Kiss, Mukuroji extract, Melissa extract, Peach extract, Cornflower extract, Eucalyptus extract, Yukinoshita extract, Yokuinin extract, Artemisia extract, Lavender extract, Apple extract, Lettuce extract, Lemon extract, Lotus root extract, Rose extract, Rosemary extract, Roman chamomile extract And royal jelly extract.
Biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membranes, amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidonecarboxylate , Moisturizing ingredients such as betaine, whey, trimethylglycine, oily ingredients such as sphingolipid, ceramide, phytosphingosine, cholesterol, cholesterol derivatives, phospholipids, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, Immunostimulants such as hydrocortisone, vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin C ester Vitamins, active ingredients such as allantoin, diisopropylamine dichloroacetate, 4-aminomethylcyclohexanecarboxylic acid, antioxidants such as tocopherol, carotenoid, flavonoid, tannin, lignan, saponin, α-hydroxy acid, β-hydroxy acid, etc. Cell activators, blood circulation promoters such as γ-oryzanol and vitamin E derivatives, wound healing agents such as retinol and retinol derivatives, arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, glutathione, etc. Whitening agent, cephalanthin, licorice extract, red pepper tincture, hinokitiol, garlic iodide extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivative, calcium pantothenate, D-pan Tothenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethinyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonyl acid vanillylamide, nonanoic acid vanillylamide, pyroctone Olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcin, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormone, cantalis tincture, cyclosporine, zinc pyrithione, hydrocortisone, minoxidil, monostearic acid Examples include hair growth agents such as polyoxyethylene sorbitan, mint oil, and Sasanishiki extract.

(10) Examples of antioxidants Sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolyl biguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxy Examples include plant extracts having an antioxidant effect such as toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoid, flavonoid, tannin, lignan, saponin, apple extract and clove extract.

(11) Examples of solvents Purified water, ethanol, lower alcohol, ethers, LPG, fluorocarbon, N-methylpyrrolidone, fluoroalcohol, volatile linear silicone, next-generation chlorofluorocarbon and the like.

Example 1
Preparation of rice-derived peptide To 100 g of commercially available rice-derived protein (protein content of about 70%), 900 ml of tap water was added, and an appropriate amount of proteolytic enzyme was added and reacted. Thereafter, the enzyme was inactivated, centrifuged, and the collected filtrate was pulverized by a spray drying method to obtain the rice-derived peptide of this example.
Example 2
Preparation of rice-derived protein Polished rice powder was suspended in distilled water, starch-degrading enzyme was added, stirred, cooled, and the precipitate was collected by centrifugation. After adding water and stirring to this, it washed with water by collect | recovering precipitates using centrifugation. Thereafter, drying was performed to obtain rice-derived protein (hereinafter also simply referred to as “rice protein”). Rice protein purity was 78%. In addition, the purity of rice protein was calculated by quantifying the amount of nitrogen by a known Geldar method or a method according to the method and multiplying by the nitrogen coefficient (5.95).

Test example 1
The rice-derived peptide of this example (hereinafter simply referred to as “rice peptide” in this example) was administered to mice. Thereafter, the body weight of the mice was measured. The results are shown in Table 2 and FIG. 1 (body weight). As a comparative example, the same experiment was also performed on mice that were orally administered with only a normal diet and a high fat diet.

  As shown in FIG. 1 and Table 2, the rice peptide administration group showed a tendency to suppress the increase in body weight compared to the high fat diet alone. Thereby, it was confirmed that the rice peptide has a weight gain inhibitory effect.

Test example 2
Measurement of PPARγ and GLUT4 gene expression In the mouse used in Test Example 1, the epididymis fat was extracted. Then, cDNA was prepared from the accessory testicular adipose tissue, and the effect on expression of each gene (PPARγ, GLUT4) was evaluated by RT-PCR.
Similarly, perirenal fat was extracted from the mice used in Test Example 1. Then, cDNA was prepared from perirenal adipose tissue, and the effect on expression of each gene (PPARγ, GLUT4) was measured by RT-PCR. The results are shown in FIG. 2 (adrenal testicular fat, PPARγ), FIG. 3 (perirenal fat, PPARγ), and FIG. 4 (adrenal testicular fat, GLUT4) and FIG. 5 (perirenal fat, GLUT4). In addition, as a comparative example, the same test was performed on mice with a normal diet and a high fat diet.

Test example 3
Regarding the rice peptide of Example 1 and the rice protein of Example 2, the mice reared in the same manner as in Test Example 1 were subjected to extraction of the liver and soleus muscle. Thereafter, cDNAs were prepared from liver and soleus muscle tissues, and their effects on CPT1 gene expression were evaluated by RT-PCR. The results are shown in FIG. 6 (liver CPT1) and FIG. 7 (soleus muscle CPT1). Here, CPT1 (carnitine acyltransferase 1) is an enzyme related to β-oxidation and takes in fatty acids into mitochondria, and by promoting the expression of this enzyme gene, lipid metabolism is promoted, The triglyceride concentration can be decreased, hyperlipidemia can be prevented, and weight gain can be suppressed.

  2 and 3, it was confirmed that the rice peptide suppresses the gene expression of PPARγ that promotes fat accumulation. Thereby, accumulation of fat is suppressed and it turns out that it has an anti-obesity action.

  Furthermore, according to FIGS. 4 and 5, it was confirmed that the expression of GLUT4 related to sugar uptake was suppressed. As a result, it was confirmed that the increase in blood glucose level was suppressed and that it had a diabetes-suppressing action.

6 and 7, it was confirmed that rice protein and rice peptide promote the expression of CPT1 gene in the liver and soleus muscle. As a result, lipid metabolism is promoted in the liver and soleus muscle, the concentration of triglyceride in the blood can be decreased, hyperlipidemia is prevented, and increase in body weight is suppressed.

Although the compounding example of the body weight inhibitor of this invention etc. (rice peptide) is given to the following, the following compounding example does not limit this invention.
Formulation Example 1: Chewing gum Sugar 53.0 wt%
Gum base 20.0
Glucose 10.0
Minamata 16.0
Fragrance 0.5
Rice peptide 0.5
100.0wt%

Formulation Example 2: Gummy
Reduced water tank 40.0wt%
Granulated sugar 20.0
Glucose 20.0
Gelatin 4.7
Water 9.68
Strawberry juice 4.0
Grape flavor 0.6
Dye 0.02
Rice peptide 1.0
100.0wt%

Formulation Example 3: Candy
50.0 wt% sugar
Minamata 33.0
Water 14.4
Organic acid 2.0
Fragrance 0.2
Rice peptide 0.4
100.0wt%

Formulation Example 4: Yogurt (hard / soft)
Milk 41.5wt%
Nonfat dry milk 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Rice peptide 0.4
Perfume
Water residue
100.0wt%

Formulation Example 5: Soft drink
Fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
Rice peptide 0.05
Perfume
Purified water residue
100.0wt%

Formulation Example 6: Tablets
76.4 wt% sugar
Glucose 19.0
Sucrose fatty acid ester 0.2
Rice peptide 0.5
Purified water 3.9
100.0wt%

Formulation Example 7: Soft capsule
Strawberry seed oil 87.0wt%
Emulsifier 12.0
Rice peptide 1.0
100.0wt%

Formulation Example 8: Tablet
Lactose 54.0wt%
Crystalline cellulose 30.0
Starch degradation product 10.0
Glycerin fatty acid ester 5.0
Rice peptide 1.0
100.0wt%

Formulation Example 9: Oral granules (pharmaceuticals)
Rice peptide 1.0wt%
Lactose 30.0
Cornstarch 60.0
Crystalline cellulose 8.0
Polyvinylpyrrolidone 1.0
100.0wt%

Formulation Example 10: Cat food
Corn 34.0wt%
Flour 35.0
Meat meal 15.0
Beef tallow 8.9
Salt 1.0
Skipjack extract 4.0
Rice peptide 1.0
Taurine 0.1
Vitamins 0.5
Minerals 0.5
100.0wt%

Formulation Example 11: Dog food
Corn 30.0wt%
Meat (chicken) 15.0
Defatted soybean 10.0
Flour 25.0
Mosses 5.0
Rice peptide 5.0
Animal fats and oils 8.9
Oligosaccharide 0.1
Vitamin 0.5
Mineral 0.5
100.0wt%
Formulation Example 12: Cosmetic cream
Squalane 20.0wt%
Beeswax 5.0
Refined jojoba oil 5.0
Glycerin 5.0
Glycerol monostearate 2.0
Polyoxyethylene (20) sorbitan-
Monostearate 2.0
Rice peptide 2.0
Preservative appropriate amount
Perfume
Purified water residue
100.0wt%

Formulation Example 13: Lotion
Ethanol 5.0wt%
Glycerin 2.0
1,3-butylene glycol 2.0
Polyethylene oleyl ether 0.5
Sodium citrate 0.1
Citric acid 0.1
Rice peptide 0.1
Purified water residue
100.0wt%

Formulation Example 14: Body gel
Macadamia nut oil 2.0wt%
Octyldodecyl myristate 10.0
Methylphenylpolysiloxane 5.0
Behenyl alcohol 3.0
Stearic acid 3.0
Batyl alcohol 1.0
Glyceryl monostearate 1.0
Tetraoleic acid polyoxyethylene sorbit 2.0
Hydrogenated soybean phospholipid 1.0
Ceramide 0.1
Retinol palmitate 0.1
Preservative appropriate amount
Centella extract 1.0
Rice peptide 1.0
1,3-butylene glycol 5.0
Purified water residue
100.0wt%

Formulation Example 15: Latex
Squalane 4.0wt%
Vaseline 2.5
Cetanol 2.0
Glycerin 2.0
Lipophilic glyceryl monostearate 1.0
Stearic acid 1.0
L-Arginine 1.0
Rice peptide 0.5
Potassium hydroxide 0.1
Perfume
Purified water residue
100.0wt%

Formulation Example 16: Bath agent (liquid)
Propylene glycol 50.0wt%
Ethanol 20.0
Sodium sulfate 5.0
Rice peptide 0.5
Lanolin 0.5
Avocado oil 0.5
Dye 1.5
Fragrance 22.0
100.0wt%

  As described above, the present invention suppresses gene expression of PPARγ and GLUT4 and further promotes gene expression of CPT1. Thereby, the food and drink, the pharmaceutical, the skin external preparation, etc. which have the function which improves fat metabolism and can prevent diabetes can be provided.

Claims (5)

A weight gain inhibitor comprising a peptide derived from rice as an active ingredient. A PPARγ gene expression inhibitor comprising a rice-derived peptide as an active ingredient. A GLUT4 gene expression inhibitor comprising a rice-derived peptide as an active ingredient. A CPT1 gene expression promoter comprising a rice-derived peptide as an active ingredient. A CPT1 gene expression promoter comprising a protein derived from rice as an active ingredient.