JP2017222622A - Abca12 gene expression enhancing agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To develop and provide a novel and useful ABCA12 gene expression enhancing agent which carries out an important role in maintaining lipid homeostasis, which has high usability and can be used in a wide range of industrial applications such as, not only pharmaceutical and food products (including food and drinks for beauty and health conscious), but also beverages, and external preparations such as cosmetics.SOLUTION: An ABCA12 gene expression enhancing agent comprises an extract from grape fruit, in particular Chardonnay or Niagara fruit pressed residue as an active ingredient.SELECTED DRAWING: None

Description

  The present invention relates to an ABCA12 gene expression promoter containing an extract from grape fruit press residue as an active ingredient.

  In order to maintain their functions, cells selectively transport ions and nutrients and discharge waste products and toxins by means of membrane transport proteins called channels and transporters. As one of the membrane transport proteins, ATP-Binding Cassette (ABC) protein is known. It has been reported that this protein functions as a transporter that actively transports various lipid-soluble low molecular weight compounds mainly using the hydrolysis energy of ATP. ABC proteins are present in a wide range of organisms from bacteria to mammals, and are involved not only in channels and receptors but also in all transport of lipids, bile salts, conjugates, drugs, and the like. Therefore, it is known that abnormalities in ABC protein genes are associated with diseases. Particularly in humans, ABC protein abnormalities are caused by various diseases, and thus are considered to be physiologically very important.

  It has been clarified that ABC protein has 48 or 49 ABC protein genes on the human chromosome. These ABC proteins are divided into seven subgroups A to G based on the homology of the amino acid sequence of the ATP binding region. Among them, ABCA12 plays an important role in maintaining lipid homeostasis in humans, and has been reported to be expressed in the stomach, skin, large intestine, placenta, testis, fetal brain, and the like (Non-patent Document 1). ).

  In rodents and the like, ABCA12 (hereinafter simply referred to as ABCA12) is expressed mainly in the stomach and skin at 18.5 days of gestation, and not only in the skin and stomach but also in the heart, intestine and kidneys after maturation. It is strongly expressed and is also observed in the brain, liver and lung (Non-patent Document 2). In particular, hyperkeratinization of the epidermis and gastric mucosa is observed as a disorder in ABCA12 knockout mice. As a typical disease caused by abnormal ABCA12 in humans, the lipid that is the key to the skin barrier is not sufficiently transported, and the lipid layer is not well formed. A skin disease called clown-like ichthyosis has been reported that is covered by the stratum corneum and exhibits symptoms such as eyelids and lips turning up (Non-patent Document 3).

Identification and characterization of a novel ABA subfamily member, ABCA12, located in the lamellar ichtyosis region on 2q34. Annilo T. et al. Cytogenet. Genome Res., 98: 169-176 (2002) Endogenous β-glucocerebrosidase activity in Abca12 epidermis elevates ceramide levels after topical lipid application but does not restore barrier function.Haller J.F. et al. J. Lipid Res., 55 (3): 493-503 (2014) Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer.Akiyama M. et al. J. Clin. Invest., 115 (7): 1777-1784 (2005)

  From these facts, it is conceivable that various abnormalities occur in the epidermis, stomach and the like when ABCA 12 is lowered due to various internal and external factors and its function fails. Therefore, it is considered possible to improve abnormalities observed in these organs by targeting the stratum corneum including organs such as skin and stomach and directly promoting the expression of ABCA12 gene.

  Accordingly, an object of the present invention is to develop and provide ABCA12 gene expression promoters that are new and useful, have high utility, and can be applied in a wide range of industries.

  As a result of intensive investigations on the search for a natural substance excellent in the effect of promoting ABCA12 gene expression, the present inventor has found that an extract from a pressed residue of grape fruit, in particular Chardonnay fruit or Niagara fruit, has ABCA12 gene expression. It has been found that there is an excellent effect of promoting.

  The present inventors further provide a preparation for promoting direct expression and synthesis of ABCA12 in an extract from water, hydrophilic 1,3-butylene glycol (BG), ethanol, or a mixture thereof. Therefore, it is extremely useful and can be applied in a wide range of industries. The ABCA12 gene expression promoter according to the present invention can be used not only for pharmaceuticals and foods (including beauty and health-oriented food and drink) but also for external preparations such as beverages and cosmetics.

It is the figure which evaluated the expression level of ABCA12 gene when adding Chardonnay, Niagara, Pinot Noir, Merlot, and Cabernet Franc using the human epidermal keratinocyte HaCaT by quantitative PCR (polymerase chain reaction method). . As a control (comparative control), a 30% 1,3-butylene glycol (1,3-BG) aqueous solution as an extraction solvent was prepared under the same conditions and used in the test. All samples were added at a final concentration of 0.25%. Using the human epidermal keratinocyte HaCaT as the Chardonnay extract from the grape fruit press residue of the present invention, the ABCA12 gene expression relative amount by adding the Chardonnay extract extracted with various concentrations of 1,3-BG aqueous solution It is the figure evaluated by quantitative PCR method. As a control (comparison control), a 90% 1,3-BG aqueous solution as an extraction solvent was prepared under the same conditions and used in the test. All samples were added at a final concentration of 0.5%. Using the human epidermal keratinocytes HaCaT as the Chardonnay extract from the grape fruit press residue of the present invention, the quantitative expression of the ABCA12 gene expression relative to the Chardonnay extract added with various concentrations of ethanol aqueous solution FIG. As a control (comparison control), a 90% ethanol aqueous solution as an extraction solvent was prepared under the same conditions and used in the test. All samples were added at a final concentration of 0.1%. When the extract from the grape fruit press residue of the present invention is Niagara using the human epidermal keratinocytes HaCaT, the ABCA12 gene expression relative amount by adding Chardonnay extract extracted with 1,3-BG aqueous solution of various concentrations It is the figure evaluated by quantitative PCR method. As a control (comparison control), a 90% 1,3-BG aqueous solution as an extraction solvent was prepared under the same conditions and used in the test. All samples were added at a final concentration of 0.5%. Using the human epidermal keratinocytes HaCaT as the Niagara extract from the grape fruit press residue of the present invention, the quantitative expression of ABCA12 gene expression relative to the addition of Chardonnay extract extracted with various concentrations of ethanol aqueous solution FIG. As a control (comparison control), a 90% ethanol aqueous solution as an extraction solvent was prepared under the same conditions and used in the test. All samples were added at a final concentration of 0.1%.

  The extract from grape fruit press residue used as an active ingredient of the preparation of the present invention is most preferably a Vitaceae Gratis Chardonnay, or Vitaceae Vitis The pressed residue produced after squeezing Niagara and squeezing the pulp and fruit juice, that is, may contain infarcts, fruits, fruit juices, pericarps, fruit nuclei, seeds, or a mixture thereof. What you extracted is good.

  Alternatively, in addition to the Chardonnay or Niagara, the Sauvignon Blanc of Vitis vinifera, Riesling, Kerner, Cabernet Sauvignon, Cabernet Franc, Merlopinoir, or Yama Grapes, or Koshu, Muscat Berry Varieties such as A, Campbell Early, Muscat Alexandria, Kyoho, or Concord may be used. Among them, representative examples are extracts from Pinot Noir, Merlot and Cabernet Franc fruit press residues.

  As the extraction solvent, water, a hydrophilic organic solvent, or a hydrous hydrophilic organic solvent can be used. At that time, in order to avoid denaturation of the extract, it is preferable to extract at a temperature close to room temperature.

  Examples of water that can be used as the extraction solvent include pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, as well as those subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering, and the like. Accordingly, the water that can be used as the extraction solvent in the present invention includes purified water, hot water, and ion-exchanged water.

  Examples of hydrophilic organic solvents that can be used as the extraction solvent include lower aliphatic alcohols having 1 to 3 carbon atoms such as methanol, ethanol, propanol, and isopropanol, and 2 to 2 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin. 4 polyhydric alcohols and the like.

  When a hydrous hydrophilic organic solvent is used, the mixing ratio can be adjusted as appropriate. From the results of Examples described later, extraction with 30 to 50% 1,3-BG or 30 to 90% ethanol is possible. Most preferred.

  The extraction is not particularly limited as long as the soluble component contained in the grape fruit pressing residue can be eluted in the extraction solvent, and can be performed according to a conventional method. For example, an extract can be obtained by immersing a grape fruit pressing residue in an extraction solvent of 2 to 10 times (mass ratio), extracting a soluble component at room temperature, and then filtering to remove the extraction residue. If necessary, treatments such as dilution, concentration, drying, and purification may be performed according to conventional methods. In this way, an ABCA12 gene expression promoter can be obtained.

  The ABCA12 gene expression promoter according to the present invention is used for external preparations such as pharmaceuticals, foods (including beauty and health-oriented foods and beverages), beverages and cosmetics. Specific examples of food and drink include nutritional supplementation, nourishing tonic, fatigue recovery, constitution improvement, whitening, skin beautification, hair cleansing, hair growth / restoration, slimming, mental stability, and other beauty / health-oriented processed foods, supplements, nutrition assistance In addition to foods and drinks, seasonings such as sprinkles, deep-fried seasonings, herb salts, sauces, dressings, etc., general preference foods or beverages such as gums, candy, yogurt, tablets, soft drinks and the like are listed.

  Specific examples of external preparations such as cosmetics include 1) topical or systemic external preparations, skin cleansing agents, skin cosmetics, 2) medicinal or cosmetic preparations applied to the scalp and hair, and 3) baths. Medicinal or cosmetic bath preparations used in hot water 4) Deodorant / deodorant for human body 5) Medicinal or cosmetic oral preparations such as dentifrices, mouthwashes, gargles, etc. 6) Skin It can be used by being appropriately blended with a sticking sheet, a cosmetic sheet, a cosmetic cotton, a sanitary article, sanitary cotton, wet tissue and the like. Ampules, capsules, powders, granules, solids, solutions, gels, bubbles, emulsions, sheets, mists, sprays, etc.

  Such external preparations include basic cosmetics such as creams, gels, ointments, liquid external preparations, lotions, emulsions, creams, ointments, gels, lotions, oils, packs, mists, facial cosmetic sheets, etc. , Shaving agents, facial cleansers, skin cleansers (including soaps), shampoos, rinses, hair treatments, hair styling agents, permanents, hair nickings, hair dyes, hair restorers Makeup cosmetics such as foundation, lipstick, blusher, eye shadow, eyeliner, mascara, perfume, skin deodorant, antiperspirant, bathing agent, mouthwash, toothpaste, mouth freshener, etc. .

  When the ABCA12 gene expression promoter according to the present invention is applied to external preparations such as pharmaceuticals, foods and drinks, and cosmetics, the components and additives exemplified below can be arbitrarily selected and blended as necessary.

(1) Various fats and oils Avocado oil, almond oil, fennel oil, sesame oil, olive oil, orange oil, orange rafa oil, sesame oil, cocoa butter, chamomile oil, carrot oil, cucumber oil, beef tallow fatty acid, cucumber oil, safflower oil , Shea fat, liquid shea fat, soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, palm oil, palm kernel oil, owl, palm Oil, beef tallow, pork tallow, squalene, squalane, pristane or hydrogenated products of these oils (hardened oil, etc.).

(2) Waxes Beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax, montan wax, shellac wax, rice wax and the like.

(3) Mineral oils Liquid paraffin, petrolatum, paraffin, ozokelide, ceresin, microcrystalline wax, etc.

(4) Fatty acids Lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12-hydroxystearic acid, undecylenic acid, tall oil, lanolin fatty acid Synthetic fatty acids such as natural fatty acids such as isononanoic acid, caproic acid, 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid and isopentanoic acid.

(5) Alcohols: natural alcohols such as ethanol, isopyropanol, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, phytosterol, phenoxyethanol, and synthetic alcohols such as 2-hexyldecanol, isostearyl alcohol, 2-octyldodecanol .

(6) Polyhydric alcohols Ethylene oxide, ethylene glycol, diethylene glycol, triethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, polyethylene glycol, propylene oxide, propylene glycol, polypropylene glycol 1,3-butylene glycol, pentyl glycol, glycerin, pentaerythritol, threitol, arabitol, xylitol, ribitol, galactitol, sorbitol, mannitol, lactitol, maltitol and the like.

(7) Esters Isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyl decyl dimethyloctanoate, cetyl lactate, myristyl lactate, Diethyl phthalate, dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate, and the like.

(8) Metal soaps Aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate, zinc laurate, zinc undecylenate and the like.

(9) gum, sugar or water-soluble polymer compound gum arabic, benzoin rubber, dammar gum, guaiac oil, Irish moss, karaya gum, tragacanth gum, carob gum, quinseed, agar, casein, lactose, fructose, sucrose or ester thereof, Trehalose or derivatives thereof, dextrin, gelatin, pectin, starch, carrageenan, carboxymethyl chitin or chitosan, hydroxyalkyl (C2-C4) chitin or chitosan to which alkylene (C2-C4) oxide such as ethylene oxide is added, low molecular chitin Or chitosan, chitosan salt, sulfated chitin or chitosan, phosphorylated chitin or chitosan, alginic acid or salt thereof, hyaluronic acid or salt thereof, chondroitin sulfate or salt thereof, heparin, ethylcellulose, methylcellulose, carboxy Polyalkylene such as methyl cellulose, carboxyethyl cellulose, sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, crystalline cellulose, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylate, polyethylene oxide and polypropylene oxide Oxide or its crosslinked polymer, carboxyvinyl polymer, polyethyleneimine and the like.

(10) Surfactant Anionic surfactant (alkyl carboxylate, alkyl sulfonate, alkyl sulfate ester salt, alkyl phosphate ester salt), cationic surfactant (alkyl amine salt, alkyl quaternary ammonium salt), amphoteric Surfactant: Carboxylic acid type amphoteric surfactant (amino type, betaine type), sulfate ester type amphoteric surfactant, sulfonic acid type amphoteric surfactant, phosphate ester type amphoteric surfactant, nonionic surfactant ( Ether type nonionic surfactant, ether ester type nonionic surfactant, ester type nonionic surfactant, block polymer type nonionic surfactant, nitrogen-containing type nonionic surfactant), other surfactants ( Natural surfactants, protein hydrolyzate derivatives, polymer surfactants, surfactants containing titanium and silicon, fluorocarbons System surfactant), and the like.

(11) Various vitamins Vitamin A group: retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A), vitamin B group: thiamine hydrochloride, thiamine sulfate (vitamin B1), Riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acid, nicotinic acids, pantothenic acids, biotins, choline, inositols, vitamin C group: vitamin C acid or derivatives thereof, vitamin D group: Ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), dihydrotaxosterol, vitamin E group: vitamin E or derivatives thereof, ubiquinones, vitamin K group: phytonadione (vitamin K1), menaquinone (vitamin K2), me Dione (vitamin K3), menadiol (vitamin K4), other essential fatty acids (vitamin F), carnitine, ferulic acid, .gamma.-oryzanol, orotic acid, vitamin P such (rutin, eriocitrin, hesperidin), vitamin U and the like.

(12) Various amino acids Valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine , Arginine, ornithine, histidine and the like, and their amino acid derivatives such as sulfate, phosphate, nitrate, citrate or pyrrolidone carboxylic acid.

(13) Various additives derived from plant or animal raw materials These are processed in a conventional manner according to the type and form of the product to be added (for example, grinding, milling, washing, hydrolysis, fermentation, purification) , Compression, extraction, fractionation, filtration, drying, pulverization, granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization, etc., arbitrarily selected and combined), arbitrarily selected from various materials You can use it.

  In obtaining an additive derived from a plant or animal material, the solvent used for extraction may be selected in consideration of the intended purpose, type, or subsequent processing of the product to be provided. Water, methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol, isobutanol and other lower alcohols or hydrous lower alcohols, propylene glycol, 1,3-butylene glycol, glycerin and other polyhydric alcohols or hydrous polyhydric alcohols, acetone, It is desirable to use one or a mixture of two or more selected from various organic solvents such as ethyl acetate. However, when it is not preferable to contain an organic solvent depending on the application, it is sufficient to use only water or ethanol that can be easily removed after extraction, and it may be used alone or in any mixture with water. The thing extracted and extracted may be sufficient.

  When using additives derived from plant or animal materials for external preparations such as systemic or topical cosmetics, it protects skin and hair, moisturizes, improves touch / feel, imparts flexibility, eases irritation , Aroma stress relief, cell activation (cell aging prevention), inflammation suppression, skin and hair quality improvement, rough skin prevention and improvement, hair growth, hair growth, hair loss prevention, glossiness, cleansing effect, fatigue In addition to cosmetic effects such as relaxation, blood flow promotion, and bathing effects, effects such as flavoring, deodorization, thickening, antiseptic, and buffering can also be expected.

  In foods and drinks, nutritional supplementation, fatigue recovery, tonicity, cell activation (cell aging prevention) and other healthy and cosmetic effects, as well as taste improvement, color tone, aroma, gloss, stabilization, thickening, antiseptic, etc. Can be used for the purpose. In addition to this, we expect various cosmetic and pharmaceutical effects of each of the raw materials known so far, and by combining these, we aim to enhance the target effect or to have a multifunctional effect It is also possible to make a product that expects

Specific plants (herbal medicines) as raw materials include, for example, almonds (toen), ai (indigo leaves), aokazura (Keifu Fuji), Aoki (Aoki), Aogiri or Kenashia Ogiri (Ao Tung), Aotsu Samurai (wooden candy) , Aotenma, acacia, red ginseng, red spruce `` fruit '', red clover, red grapes, red ginseng (logwood), red wrinkles (red buds), red crested or red crested or reddish (root), red crested or reddish (ground yellow), Agi (Aki), Aki larch, Akinire (crusted skin), Aguay Guassou, Aguahe (Omiten coconut palm), Akebi (Kitsu), Asa (Asakojin), Maruba morning glory or morning glory (Chicken), Hydrangea (hydrangea), Ashitaba (Tomorrow), Azuki (Red Azuki), Asunaro, Acerola, Asenyaku (Asenyaku), Athira (Shokuyokanna), Anise, Abiyu, A Biurana, oilseed rape, Abemaki `` fruit '', avocado, ama, achacha (Amacha), Achacharu, Amadokoro (Jade bamboo), Amana (a light-hearted), amaranth (Hyuyu, Hagatetou, Himogeito, Senninkoku, Sugimorigateto, Hosoaogeito, Hasoagoito Aozulan, Amaranthus hypochondriacus), Amigasayuri or Baimo (shellfish mother), Aristolomeria (Yurizuisen), Arcana (Alcanna), Algarrobo (Cabe), Altea, Arnica, Alpinia or Katsumadai (Suzukuku), Aloe (蘆薈), Aloe vera, angelica, apricot or honanzu (Anzujin), Ansokkou (benzoic incense), yellow support, igakozolina (geo-biliary head), licorice or gecko licorice (indian oyster), rush (light heart grass), itadori (tiger cane root), yew (one Place), Strawberry, fig (no flower `` fruit, leaf ''), Ichihatsu (first), Ichibi (winter lion), Ichiyakusou (one medicinal herb), ginkgo (Ginkgo `` seed, leaves ''), Japanese yellow peas (distant), carob, Japanese beetle ( Taillexi), Inubiyu (Honagainubiyu), Rice `` Seeds, Seed coat '', Inondo `` Seeds '', Ibuki-so-sou, Nettle, Ylang-ylang, Iwa-tobacco (Iwabuchi), Iwahiba or Iwamatsu (rolling mushroom), kidney beans, oolong tea, fennel (mustard) , Wheat (Chibusanoki), Ukiyara (Sanryo), Uguisukagura `` Fruit '', Himewikyo, Turmeric (Urban), Duckweed, Usubasaishin or Keirinsaishin or Oshusaishin (spicy), Usvenia Oy, Usbeni Hollyhock, phalaenopsis, weevil (summer hay), udo or shishiudo (gung, alone, tangy), unyadegato (unkari) A, Cat's Claw), Uba tea, Ume (Japanese apricot `` seed, pulp ''), Japanese white beetle, Uwaurushi (Kusako-kemomo), Unshuumika (Chen), Unboku, Estragon, Ezoukogi (Tomogoka), Ezo-suzuran, Echinashi (Hosobamurasaki Barengiku) , Enishida, Enokitake (榎 茸), Ebisugusa or Cassia Tora (Keiko), El Campre, Elderberry “fruit”, Elemi, Elingi or Pre-Lotus Elinji, Enju (Safflower, Camellia rice), Pea, Ogi or Kibanaogi (Yellow Twilight), Naruko Yuri or Kagura-mabanaru Koyuri (Yellow), Ohisasa Yuki or Sasano Yuki, Ouren (Yo Ren), Ogata Houken, Okarasuri (Karokon), Oguruma (Civil Works Incense), Otsu Samurai (Prevention), Psyllium , Car forage), toucan thistle (Zhengzhou leakage, bald eagle), toucan Mi (coconut palm), Toucan cactus, Ovana okera or okera (white moth), Osara squirrel (Banaba), Ooyabaya shabushi "fruit", Oohashigusa (cereal sperm), Omia catechu, Oomihasa or hawthorn (Mountain vegetation), Omiyashi, Omiji Barley), Oka, Okazeri (snake bed), Okra `` fruit '', Oguruma (overturn), Oguri higotai (Zhengzhou leakage, indigo head), Panax ginseng or Tochibaninjin (Ginseng), Hypericum pertussis or Pterotus pertussis or Hypericum perforatum (Brother cut grass), Odorikosou (continuous), Onamomi (Circle ear), Onigomi, Onikoro or Tokoro or Nagadokoro (Hikai), Oninoyara (Tempa), Onyuri or Sasayuri or Hakatayuri (Yuri), Onoelan, Ononis, Halibut楡), Ominae (losing sauce), Yuuko, Dutch mustard (watercress), Ora Dazelli, Dutch beech, Dutch bees, olives `` fruit, seeds, leaves '', oregano, orange `` fruits, peels '', silkworm (ripe yellow), cacao `` fruits, peels, seeds '', oysters (bamboo `` leaves ''), Kagi-Kazura (Katsufuji), Kakidooshi or Kantorisou (Lotus), Kakiran, Gaku Hydrangea, Cassia, Casinoki (fruit berries), Gadju (Kashiwa), Kashiwa (Kashiwagi, Kashiwa), Cascarilla, Cascala Sagrada, gypsophila, gypsophila, cynomolgus (Kinshato), kaniwa, carnation, valerian (valerian), hippopotamus, birch or fern birch (white birch), gerbera, pumpkin, kapokoki `` seed '', kahoku salamander (蜀椒), gama Yellow), chamomile or roman chamomile, chamomile (weed), cam cam (camo duck), collar, chrysanthemum, calla or cinnamon , Oat biscak (half summer), oats, guarana `` seed '', carahoo (kokubaku), karaya, galyu, karin (garden), garcinia, kawamidori, kawara-saiko (reeled rape, white millet), kawajisha, kawaratake, kawaranadeshiko ( (Stone bamboo) or Ezokawaranadeshiko (buckwheat noodles, buckwheat), Chinese carrot (blue potatoes), Chinese mugwort (bamboo chin mackerel), kansui (kansui), licorice (licorice), kantarasa, candelilla, kanto, canna, kanran, raspberry (ezo strawberry) , Dutch Strawberry, Shrimp Strawberry, Nawashiro Strawberry, Momiji Strawberry, European Raspberry Strawberry), Kiwi `` Fruits, Leaves '', Kikarasuuri (Gurone), Chrysanthemum (Kikyo, Kikyo-root), Chrysanthemum (Chrysanthemum, Chrysanthemum, Datura), Kikutanigiku, Kisage (Salmon), Gigigishi (sheep hooves), pheasant (salmon), Kizuta, Kidachi aloe, Kidachi mint , Quina, linden (shinkona, red linden), quinoa (quinoa), yellowfin (yellow tuna), bean, gymnema sylvester, kimenkaku, cabbage, cabbage `` unripe fruit '', caraway, cucumber, gyory (Nishikawa willow, tail willow), Kiraja saponaria, Kiraya, Kiransou (Kinza small grass), Kumquat `` fruit '', Kinkiju, Ginseikai, Kimbusen, Kinma, Kinkihiki (Sentsukusa), Kinlan, Ginlan, Ginryohen, Guapeba Vermela, Guava `` Fruit '', Guayule, Quercus・ Infectria (garlic pods), kukui nuts, kugenumaran, wolfberry (bamboo shoots, coconut palm leaves, cocoon leaves, ground bone skin), cedar casserole (Tenmon winter), kudu (kudzu), camphor tree, gooseberry `` fruit '', ginseng (yellow flower candy) ), Kutiti River, Gardenia (Yamako), Kunigi (Kusou), Kupu , Kubeba, Kumazasa, Kuma-tsutsura (horse whip grass), Clara (bitter), cranberry `` fruit '', chestnut `` seed, fruit, astringent skin '', curcumigo latifolia `` fruit '', grapefruit `` fruit and leaf '', buckthorn, kuroganemochi ( Rescue), Kamehiba Kokoshi or Kurobana Hikikoshi or Hikiokoshi (prolonging grass), Clove (clove, clove), Gumbai Tuna (Sekimei, Sekimeishi), Keigai (Kashiwa, Hakuho), Celosia (Chicken flower, Chicken crown), Gekkavidin, Gecko (Laurel Tree), Kenashi Sartoribaira (Dogo, Mountain Return), Gentiana, Gennoshouko (Old Grass), Kemponashi (Kigushi), Kokisekoku, Kishimizukan (Koji, Tachibana, Obenimikan, Fukurimikan, Sagamikouji, Ponkan, Santara Skin) ), Koshinbara (monthly flower), Koiusui mint, Kozo `` Fruit '', kocha (tea), kohone (river bone), koh hong (Tsubakimoto, Karamotomoto), Kouriang, Kouryokyo (Koryo), cilantro `` fruit '', Koouren (Huo Ren), Koganebana (Yellow Gon), cowberry (Etsu) Tachibana), Coco `` fruit '', Goshuyu (Kurei), Gosho strawberry (Golden bonsai), Pepper (Pepper), Cosmos, Copaiba balsam, Coffee `` Seeds, leaves '', Kobushi or magnolia (hot pepper), Burdock (Beef bowl, Gyudon) ), Coconut lees, sesame (sesame seeds), sesame seeds (genus ginseng), trash (goji), saneka or binankazura or pine bush, wheat (wheat), rice or rice bran `` red potato, white birch '', rice oil, cola acminata `` seed '' , Cola Bella "Seeds", Colony Lilla, Koroha "Fruits", Colombo, Conzurango, Kombu, Konjac, Comfrey (Chang Zhang grass), Sisal (Sisal Asa), Cy Hailan Sakaneran (Ezosakaneran), Sasima button eel or Sina button eel or Cinnamon ginseng (weikensen), Sakura (Ooshima cherry, Yamazakura, Oyamazakura, Edhigashi, Mamezakura, Miyazakura, Someiyoshino, Takanezakura, Kasamikan, Sakura, Sakura, Sakura Fruit, bark (cherry bark) ''), cherry, pomegranate, sasa, sababagin orchid, sasanqua, sardine sardine (salmon), sweet potato, sugar cane, sugar beet, sunflower jujube (saccharin), saffron (bancho flower, west safflower), sapodilla, sapotea mariyo , Pomelo `` fruit '', savonso, salmon berry `` fruit '', salamander (sasma), salamander (sand indigo sashimi), salvia (sage), scallops (bamboo rape), sawagurumi (wild walnuts), sankaku cactus, sangre Degrad ( Loton), Salamander, Sansino Ginseng (37 ginseng), Sanshuyu (Yamamuro), Sansho (Yamamuro), Sandskon (Yamazune), Shea (Kalite), Cyano `` fruit '', Shiitake mushroom (Shitake), Sion (Purple spider), winged bean, jikitarisu, shikunshi (messenger), perilla or ajizo or chimmentiso or catamenzo (purple leaf, shisoko), rosewood, linden tree, red-faced syringae, renilla (ream), shimeji (hinshimeji, shakashimeji, hatake-shimeji Shimeji, beech shimeji, honjimeshi, shirotamogitake, shimokren (hot pepper), shimotsuso, potato, shajin (shasan), jasmine (matsurika), janohi (barley winter), jury scorpion, shrimp swordfish, sand , Shredded sand), juzudama, palm "fruit", shung lan, jujuu palm, show (Ginger), Zodiac hydrangea (Tsuneyama), Shobu (bamboo shoot, Sone), Shozu `` fruit '', Shirakashi `` Seeds '', Silane (Bikkyu), Shirogori `` Seeds '', White clover (Clover), White clover (chicken bone grass) , White squirrels (smoke squirrels), Shirobanatsuta "flowers", Shirobana Lupine, Shirominanten (southern Tenmi), Cinconacylbra, Ginkgo biloba (Mizuka, Suzuka, Senncho), Cinnamon, Cinnamomum cassia (Kaishin), Suika , Honeysuckle (gold and silver flowers, Shinobu winter), sorrel (acid model), swim berry `` fruit '', star apple, stevia, strawberry `` fruit '', succulent (Xu Longan), sugina (question), purslane (horse tooth soap, horse tooth soap Child), plum "fruit", sulgaran (oran), Japanese red pine "ball cone", Japanese larch, Japanese kizuta, Japanese seiyo Walnut, hawthorn, cypress, dandelion, horse chestnut (maronier), pear `` fruit '', sunflower, elder, scallop (juniper, pine), yarrow (milfoil), rose, antelope Japanese butterfly, Japanese mistletoe, American mint or Atlantic mint Sarcophagus), cedron (Boushuboku), mallow, hirohasenega, senega, seri, celery, nematode (river cucumber), senshinren (pure ream), sendan, sennin cactus, Nanna `` fruit, leaf '', ginseng (daikon), sea bream (medicated), senboku, soka (grass), elephant chrysanthemum, prawns, buckwheat `` seed '', potato monogram, broad bean, daiou (daihuang), radish, soybean, daidai (Orange peel, fruit), Takasago Gurihigotai (Southeast Indigo Sashimi), Takasaburo (Cirrus Lotus), Takatodai (Oyodo), Takarabi (Cirrus spine), Dark Sweet Cherry `` Fruit '', Japanese hollyhock, Tachikoso (Time, Hundred incense), Tachidokoro (Hikai), Tachiyanagi, Tamarind `` Seeds '', Onion, Tamshiba (hot pepper), Taranoki `` Fruits, leaves, root bark '', Tarayo (Large winter blue, Ichiha tea, bitter tea, bitter tea), Dahlia (Tenjiku button), Tarwi, Tankimi, Tanshiwiwa, Tanjin (Tanjin), Dandelion (Shinko), Shirobana Dandelion or Mouko Dandelion, Danmaru, Cherry , Imperata "fruit, roots, buds", the district Seth carrot (Takefushi carrots), chicory, chunker Piedra
(Kidachi Kumiso), Tulip, Chono Stay, Datura Thistle (Artichoke), Datura (Dark Yellow), Datura (Amber), Datura Worm, Choreimaitake (Amber), Chorogi, Azalea, Azalea, Tsukuritake (mushrooms), Tsuchiakebi, camellia, camellia, clover (lacquered grass), camellia (duck-weed), Tsuruzuki (red bean), Tsurutsukikibi, Tsurudokudami (what neck rice cake), Tsuruna (Apricot apricot), Tsuruninjin (four leaf ginseng), Tsuruma, Tsuwabuki, Deiko, Teuchigurumi, Duberry `` Fruit '', Tengusa, Tencha (bamboo tea), Tendai-yaku (glaze), Toga (winter coconut), Tokagi quail, Capsicum (banban), Toki (toll), Tokinsenka (Tokinsenka) Marigold), red croaker, touna bena (river cut), corn or corn hair (Southern lashes), horned potato (Sadako), Torindo or Ginseng (Dragon gall), Tokusa (wood band), Dokudami (10 medicines), Tokushi (Nippaku), Toshishi or Mamedaoshi or Nekazura, Tochu (bark, bark, Leaves, roots ''), ash (crusts), tomatoes, tragacanth, triacanthos `` seed '', Turkish almonds, tormentilla, dronoki, troro mallow, tonka bean, nigerian berries `` fruit '', Chinese yam or wild yam (wild boar), nagii kada (butcher bloom) ), Naginata Koju, Nazuna, Rapeseed, Natsume or Vertical Spider (Sword Bean), Natsumikan, Jujube (Otsugi), Naniwaibara (Golden Cherry), Navena (Suspended), Nameko, Nankin Bean (Peanut), Nanten (Southern Fruit), Namban Karamushi (Sesame), Niosumire, Nigaki (Nakiki), Nigamugi (Sweetness), Nikuzuku, Kei or Nikkei or Seika Ronnikei or Yabunikei (Cinnamon) or Keishi (Keishi branch), Flying tiger plover, leek (lion), elderberry (bone, `` fruit, flower, stem, leaf ''), garlic (large persimmon), Nurde (penta), leek, nemonoki Or Nebu or Nebi or Nemurino or Digokubana (community), Noazami (Daisetsu), Nobara (fruit), Nozenkazura (Lingen flower), Nogateto, Yarrow, Nodake (former cucumber), Novara, Peach, Pineapple `` fruit '', Hibiscus (Busouge) , Fulinbussouge, Roselle), Hailindo, Hauchiwa, Pau Dorse, Hakama Labosi (osteostomy), Hakukayumatou, Chinese cabbage, Chinese cabbage (white tinea), Hakulberry `` fruit '', Japanese crocodile (breeding), Habami (coconut), Hasidorokoro (Roof root), basil, lotus (lotus, lotus meat, lotus), parsley (holland jellies), hadakamugi, batata, bee or maize Ke (bamboo shoots), patchouli, mint (thin-load, thin-leaves), yellow peas, pearl barley (Yokuinin), Hanasuge (my mother), bananas, hanahakka, Hanabishi (Sitoshiri, Shitsutsuri), vanilla bins, papaya, scallop , Pahalobobo, hub `` whole grass, stem, leaf '', paprika, oysters, hamago or honey bee (Vulgaris), hamasge (Katsukiko), Hamabishi (Shitsuko), Hamanasu (Maikai flower), hamabofu (hamafufu), Hamamelis, palm, rose (rose), balata, balata rubber tree, agaric (agaric, white-faced agaric, quince) (Skin, maple leaves), Barbasco, Harlindow, Handaikai (Taiho Sea), breadfruit, hinoki Sea urchin (hiboshi), lizard carrot (participant), pecan nuts, ganbanana (stone urchin, vine pearl shahua), higurmadaria, higotai, hishi (hishimi), pistachio, beet, human lizard (hisarium), human winged fern, daisies (Daisy), Hinata Taikozuchi (cow knee), chickweed, cypress, hiba, castor, sunflower, bell pepper, Himezu (Tengu), Himamatsu (Kaori), Himematsutake (Kawariharatake, Hiromatsutake), Himemuyoran, Pimenta `` fruit '', Beakshi, beakkyu, jade "fruit", chickpea, lentil, bellowed oyster, hirohaokinagusa (bald eagle), loquat "fruit, leaf, stem", betel nut (large clothes skin, coconut), puer tea (common tea), sweet pod (Southern rattan), Japanese cypress, Japanese cypress poppo (Japanese winter flower, Japanese winter leaf), Fujibakama (Orchid), Japanese bean (Japanese peas), Japanese red bean (Chujizakura, strawberry) ), Grapes `` fruit, pericarp, seeds, leaves '', beech, Fuyumushinatsusatake (Cycium Cordyceps), Brazilian licorice, Brazilian carrot, Brazilian palm, Brazilian elephant coconut, black currant `` fruit '', blackberry, Branjen, plum `` Fruit '', Fruceraria, Blueberry (Prunus serrata), Prunes, Floral Blanca, Blond Psyllium, Bundow (Mung Beans), Hazelnut, Loofah, Hetsukaran, Safflower (Safflower), Heneken, Belladonna, Berry `` Fruits '', Percea, Pervianberg , Pereschia grandifolia, red beetle or squirrel (scenic sky), boysenberry `` fruit '', scallop or narcissus or nendo or hahagigi kokia (silk), horsiran, scallop (saccharus, acute pupa, pelagic grass), pouteria・ Supporters, Po Terrier Lucuma, Spinach, Bow Fu (Windproof), Spinach, Japanese physalis (Torune), Japanese cypress (Japanese folk magnolia, Park), Bokeh (Kiso), Hosoba-Aragiku (Kayoyoku), Hosoba-oguruma, Hosobanaokera (Samurai), Hosobakirinso (Keitenzochi), Hosobabarengiku, Bodaiju (bamboo tree), button (peony `` flowers, leaves, stems, bark ''), button pi (peony skin), hop, jojoba, borage (Lurichisha), Bordeaux, howtle berry `` `` Fruit '', Hononiku (meat jutsu, large art), Honsecek (iron skin stone shark, sparrow mountain stone shark), myzurutennansho (Tennan star), Maitake (maiko), maou (mao), maca, macadamia nut, margaret (mok) (Shungiku), Makri (marine grass), Magwa (mulberry bark `` bark, leaf ''), Magnolia splengeri, Mazaran euba, Masalanzuba de Searer, Masheira de Boi Mashua (Tamanowenhalen, Kyukonkinrenka), Matatabi (wood tengu), Matsukasa, pine `` leaves, bark, root '', Matta Orillo, Matsuhodo (茯苓), Matico (Cordon sillo), Mayoram (Hanahakka), Malvano jardin (Bitter), Mulberry `` Fruit '', Quince, Malene (Biloud Mouse Squid), Mango, Mangosteen, Manzanya (Andesuka Mitsuru), Manshugurumi, Mandarin `` Fruit '', Mannentake (Ganoderma biloba), Pheasant (fruit berry `` Fruit '') , Mishimasaiko (Saihu), Mizusobako or Mizuasagao (Dongweed), Mizokakushi (Half-sided lotus), Misohagi (Chinese green), Japanese willow or Japanese willow (Henpo), Mitsugasiwa, Mitsuba, Midorisapote, Mirimaza, Mimosa, Myoga, Miracle fruit “fruit”, myrrh, mirobalan, wheat straw, mugweed (mushroom), muk Japanese cypress, mugwort (life-prolonging skin), munya, purple (purple), purple or yellow purple corn, purple corn, purple corn (Kunming chicken blood), megakansa opuntika, pheasant (maranthus), mebougi, melaroika, Melissa, Melilot, Melon `` Fruit '', Moukomomogi, Mosouchiku, Mokkirin, Mogi (Pepper), Mochinoki, Mokko (woody incense), Momijidaio, Peach (peach `` leaves, seeds, flowers, fruit ''), coconut, Morello Cherry `` fruit '', Morohaya (burlap), Yakawamura potato, Yakuchi (Michichi), cornflower (cornflower), cornflower mint, yacon, Yashabushi (Yagari) or Himeyashabushi `` Fruit, pericarp, fruit ear '', Yachiyanagi, Millet (octagonal gold plate), mistletoe (willow infestation), willow (kawayanagi, tachiyana) , Weeping willow, red willow, cat willow, dog willow, gold willow, koryanagi, unryu willow, miyagi willow, palm, willow, beech, goldfish, beef, stalk (Crane, Tenmeisei), pokeweed (commercial land), Japanese alder (Yamamuro), Japanese yam (Plum skin), Japanese mugwort, eucalyptus, Yukinoshita (tiger ear grass), yucca or flevifolia, yuzu `` fruit '', lily, yorogusa, Mugwort (Leaf), Ligan (Raimaru), Lime `` fruit '', Rye, Lacanca `` Fruit '', Raspberry `` Leaf, fruit '', Latania (Klamelia), Lackey or Shallot (Lady), Lavender, Longan (long-eyed meat), Agave (Aono Agave, Fuclin Agave) Ryokucha (green tea), apple `` fruits, seeds, leaves, roots '', gentian, lubas or suabishimusu (Suzu Ryo), Ruritama thistle (bladder tiger tai, Xinjiang indigo sashimi), litchi (toothpick, toothpick core), lettuce (chisha) , Red currant `` fruit '', red pitaya, lemon `` fruit '', lemongrass, forsythia or Chinese forsythia (ream), forsythia, wintersweet, wax palm, locon (reed, root), loganberry `` fruit '', rose Examples thereof include marie (mannenrou), rose hips (nobara), wasabi, cotton wisteria (Ming Mongolia), and bituminous (ground).

  As seaweeds, seaweed [Green algae: Chlorella vulgaris, Chlorella pyrenoidosa, Chlorella ellipsoidia, Aonori (Usba aonori, Sugiaonori, Hiraaoori, Boaonori, Hosoeda Aonori), Anaaoosa (Aosa)] (Macombu, Resilibu, Hosocome, Mitsuishi Kombu), Wakame, Hirome, Aowakame, Giant Kelp (Macrocystis Integrifolia, Neocitus Ruetkeana), Hijiki, Hibamata, Umiuchiwa, Usubaumiuchiwa Umiuchiwa, Akaba Umiuchiwa, Konami Uchiwa, Okinawa Uchiwa, Usuki Uchiwa, Etsumi Uchiwa], seaweed [Red algae: Hijirimen, Maca (Tengusa), Hiraksa, Syria, Oaxa Caterpillar, Yatabegusa, Yuukiri, Shimatengusa, Tosakanori, Togekirinsai, Amakusakirinsai, Giraffe, Juniper ginkgo rhinoceros, Tsunomata, Totsuka (Yahazutsu notamata), Ezotsunotamata, Togetu no Takita , Yaleus banori, Kagius banori, Susius banori, Haius banori, Akamo mizunori] and the like.

  Other algae, for example, green algae (Chlamydomonas: Chlamydomonas, Akayukimo, Dunaliella: Dunaliella, Chlorococcus: Chlorococcus, Kuwanomimo: Kuwanomimo, Volbox: Dandelion, Volbox, Palmera, Yotsumeo, Himidori Aoumiduro, Tsurugidomiro, Hibidoro: Hibidoro, Aosa: Anaaaosa, Amiaosa, Nagaaosa, Kawanori: Kawanori, Friccella, Shiogusa : Magatama, Dioscorea: Pheasantata, Surichogita, Heraiwata, Kurokita, Hanemo, Genus: Mill, Chromel, Sakibutimil, Nagamil, Hiramil Casanori: Casanori, Jusmo: Jujusmo, Tamajusmo, Mizojusmo, Mika ヅ kimo, Korekaete, Tsutsumimo, Kikkogusa, Humanexa : Sumiremo, Hosimidro, Fuchinashimidro etc.).

  Cyanobacteria (Suizenjinori: Suizinori, Aoko, Nenju: Kawatake, Ishijelly, Hassai, Yuremo, Rasenmo (Spirulina): Spirulina, Trichodesmium (Iaciasio), etc.

  Brown alga Sanadagusa: Sanadagusa, Fukurimamiji, Commongusa: Commongusa, Yahazugusa: Ezoyahaz, Yahazugusa, Uraboshiyahaz, Jigamusa: Jigmygusa, Umichiwagusa, Umamisakugakua, Hakusou : Navarimo, Chasomen genus: Motsuki Chasomen, Matsumo genus: Matsumo, Nagamatsumo genus: Nagamatsumo, Okinawa mozuku: Okinawa mozuku, fake Tomozuku: Niseft Mozuku, Futomozuku: Futomozuku, Ishimozuku: Ishimozuku, Kuromo: Kuromo, Nisemozuku: Nisemozuku, Mozuku: Mozuku, Ishige: Ishige, Iroro, Ichimegasa: Ichimegasa Umibosu, Urushigusu: Urushigusa, Keurushigusa, Tobaccogusa, Composita: Composita, Haberodomo: Haberodoki, Havanori: Habanori, Habanori: Habanori, Commonbukuro, Ezobukuro, Ezobukuro Chishima fukuronori genus: Chishima fukuronori, Kagomenori genus: Kagomenori, Muraridori genus: Murachidori, shark genus: shark zusa, genus genus: lobster, genus genus: yokojimamanori, Ganoderma genus: cynomolgus, fennel spider: fennel spider, vine genus: turmo, turtle genus: sea turtle, scorpion genus: sujime, misji kumbu genus: misji kumbu, atsuba misji kumbu, kumbu genus: tsutsugara kumbu, oyster kumbu, onikombu, gakonbubu Barracuda, Trollocombu: Trollocombu, Antokume: Antokume, Kajime: Kajime, Tsuruarame, Kurome, Kikuishikombu: Kikuishicombu, Nejikcombu: Nejicombu, Kuroshiome: Kuroshiome, Nekoshikonbu, Aramei Genus: Ainuwakame, Chigaiso, Oniwakame Ezoi Shige: Ezoi Shige, Yabane Moku: Yabane Moku, Rappa Moku: Rappa Moku, Joromoku: Ugano Moku, Jo Lomoku, Hiemoku, Honda Walla: Tamanashimoku, Isomoku, Nagashimamoku, Akamoku, Shidamoku, Honda Walla, Nejimoku, Narasamo, Mametawala, Tatsukuri, Yatsumata Moku, Umitora no Moku, Fushishimoku, Mohmokumoku, Hahamokumoku , Ukimo: Ouokimo, Burukimo: Burukimo, Kayamonori: Kayamonori, etc.).

  Red algae Genus: Sea urchins, Tsukumonori, Anemone crickets, Astragalus, Amaranthus, Amaranthus, Agaricata Genus: Tamaitadaki, Kaikekenori Genus: Kaginori, Kaikekenori, Tengusa: Himetengususa, Hytengususa, Oobusa, Nambugu , Kohira, Yohira, Kinukusa, Hibirodo: Hibirodo, Himebiro, Isomumedo: Isommedo, Aedes: Rhizome, Ryumons: Ryumon, Ranunculaceae, Nisekare Naminohana: Hosobanaminohana, Naminohana, Sangomodoki: Ragaramomodoki, Shiogusagoromo: Shiogusagoromo, Iwanokawa: Etsukiiwanawa, Kinokawa: Kinokawa, Kanonote, Sangori Kyono Shiro, Sakuranori, Nikumukade, Tambanori, Tsurutsuru, Fudarak, Marubahdarak, Isonohana: Nurakusa, Ronulaksa, Oomkadenori, Hirakintoki: Hirakintoki, Matabou: Matabou, Kintoki: Chabokintoki, Kintoki, Matsunori, Rice, Tokamatsu, Hitomatsu, Fushikintoki, Tsunomude, Nagakinito, Crayfish Nagaobane: Naganobane, Funori genus: Hanafonori, Fukurofunori, Mafunori, Karekigusa: Karekigusa, Tosakamodoki: Hosobanatosakamodoki, Hironotosakamodoki, Yatsudegatatosakamodoki, Kurotosakamodokisane, Zotosofomoza Tosakamodoki, Nankaitosakamodoki, Himetosakamodoki, Kinuhada: Kinuhada, Ezotosaka: Ezotosaka, Tsukasanori: Enashikarimenia, Otsukasanori, Hana Tacarimenia, Hoonoo: Honoo, Hikagenoit: Hikagenoit, Usuginu, Nikuhounoo: Nikuhounoo, Venus nago, Venus nago, Susca veni: Suscabeni, Okarugusa: Yamadagusa, Mirin: Mirin, Hosokamiso , Isomocca genus: Isomocca, Yukari genus: Yukari, Hosoyukari, Ibaranori genus: Ibaranori, Saidaibara, Tachiibara, Kagibaranori, Kojinoo: Kizino-o, Isodantsu: Isodantsu, Atsubanori: Atsubanori, Ogonori, Ogonori, Ogori Mizo-okonori, birch, beniogonori, fukureshinori, purple birch, shinkaibanori, spruce birch, kataogonori, ryukyuogono Li, Atlantic scorpion, Ivy genus, Yumigataonori, Kubireogonori, Mosagogonori, Kinubanori, Amanita genus: Hachijotensamodoki, Fushikenori genus: Fushikenori, Namiiwatake, Nymphalanthus Itagususa, Saimi, Hari, Lotus Jigusa: Lotus Jigusa, Sugi nori: Ikanoashi, Hosoibonori, Nobonori, Black Haginansou Genus: gourd, cherries, octopus: octopus, sedge, genus: genus, genus: goat, dals : Dulse, Scorpionus, Anadalus, Weibusa: Uebusca, Benifronori: Benifuronori, Fusunagi: Futsutsunagi, Himefusunagi, Hirohafushitsugi, Otsunagisou, Hirawatagigi, Usuwasugi , Egonori: Egonori, Futogigi, Saeda: Saeda, Chirimomiji: Chirimomiji, Konohori family: Habutaenori, Konohori, Suzuronori, Usubeni: Genus: Kagios banori, Yareus banori, Susius banori, Heius banori, Usubanorimodoki: Usubanorimodoki, Ayanishiki genus: Ayani Genus: Aeginu, Dadia: Enasidadia, Shimadadia: Isohagi, Shimadadia, Dajimodoki: Dajimodoki, Euglena: Morayogusa, Fuyugusa, Makuri: Makri, Yanaginogi, Yuna, Yukinagina , Sasabayanaginori, Sozo genus: Kurosozo, Kobsozo, Hanesozo, Sozonohana, Hanegusa genus: Hananegusa, Hananegusa, Kozanemo genus: Kozanemo, Isomurasaki, Hosozozanemo, Himegoshigusu, Giant genus Isomagusa, Suginasugusa: Suginasusa, Isobashou: Isobasho, Fujimatsumo: Fujimatsumo, Sawweed: Haeshinosakiba, Kawamoku : Kawamoku, Aokawa Mozuku, Himekawa Mozuku, Ideyugogome: Ideyugogome, Okichimozuku: Okimozu, Otosa, Chinomo: Chinomo, Chisujinori, Chisujinori, etc.).

  Axial algae (Shajikumo, Shiratamamo, Hoshitsurimo: Hoshitsurimo, Rikunotumusu, Flaskmo: Himebumo, Chaboflasmo, Tripera, etc.), yellow algae (Hikarimo: Hikarimo, etc.), etc.

  Animal-derived materials include chicken crown extract, cow or pig, human placenta extract, cow or pig stomach, duodenum, intestine, spleen extract or degradation product thereof, cow or pig brain tissue extraction Collagen hydrolysates (acids, alkalis, enzymes, etc.) of products, cattle / pigs or fish, collagen derivatives such as water-soluble collagens or acylated collagens, elastin or elastin hydrolysates of cattle or pigs (acids, alkalis, enzymes, etc.) ) Or water-soluble elastin derivative, keratin and its degradation product or their derivatives, silk protein and its degradation product or their derivatives, pig or cow blood cell protein degradation product (globin peptide), cow or pig hemoglobin degradation product (hemin) Hematin, heme, protoheme, heme iron, etc.), milk, casein and degradation products thereof or derivatives thereof, skim milk powder and degradation products thereof or derivatives thereof Lactoferrin or decomposed product thereof, egg ingredients, fish hydrolyzate, nucleic acid-related substance (ribonucleic acid, deoxyribonucleic acid), or the like.

  As a material derived from these plant or animal-based materials, any site, cell, tissue, organ, metabolite, etc. derived from a gene recombinant or a cell fusion can also be used. Furthermore, for example, an undifferentiated cell group, a cell group in the middle of differentiation, or the like obtained by culturing an arbitrary site, cell, tissue, organ or the like can also be used.

(14) Marine components Seawater such as deep seawater, for example, sea salt, dried seawater, inorganic salt (sodium chloride, magnesium chloride, potassium chloride, etc.), sea mud or mud (from the Dead Sea or Atlantic Ocean) Fango), for example, Italian mud, German fungo, Eifelfango, Freiburg fungo, etc. Sea mud or mud from various locations (containing components: silicon dioxide, titanium dioxide, aluminum oxide, iron oxide, manganese oxide, sodium oxide, potassium oxide, Magnesium oxide, calcium oxide, strontium oxide, sodium, potassium, magnesium, calcium, chromium, iron, copper, nickel, zinc, lead, manganese, arsenic, water), saintoku stone, etc.

(15) Microbial culture metabolite Yeast metabolite, yeast extract, bacterial metabolite, bacterial extract, mold or actinomycete metabolite, mold or actinomycete extract, natto metabolite, natto extract, rice fermentation extract , Fermented rice bran (red rice bran, white birch) extract, Euglena extract or decomposition product thereof or water-soluble derivative thereof, trehalose or derivative thereof, lactic acid fermentation product of raw milk or skim milk powder, fermented lactic acid bacteria of legumes, coconut plant Lactic acid bacteria fermented products.

(16) α-hydroxy acids Glycolic acid, citric acid, malic acid, tartaric acid, lactic acid and the like.

(17) Inorganic pigments Silicic anhydride, magnesium silicate, talc, kaolin, bentonite, mica, titanium mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, calcium carbonate, magnesium carbonate, yellow iron oxide, Bengala, black iron oxide, gunjo, chromium oxide, chromium hydroxide, carbon black, calamine, etc.

(18) UV absorber / blocker benzophenone derivatives (2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate, dihydroxy Dimethoxybenzophenone, dihydroxydimethoxybenzophenone-sodium sulfonate, 2,4-dihydroxybenzophenone, tetrahydroxybenzophenone, etc.), paraaminobenzoic acid derivatives (paraaminobenzoic acid, ethyl paraaminobenzoate, glyceryl paraaminobenzoate, amyl paradimethylaminobenzoate, Octyl paradimethylaminobenzoate), methoxycinnamate derivatives (ethyl paramethoxycinnamate, isopropyl paramethoxycinnamate, octyl paramethoxycinnamate, 2-ethoxycinnamic acid cinnamate) Til, sodium paramethoxycinnamate, potassium paramethoxycinnamate, diparamethoxycinnamate mono-2-ethylhexanoate glyceryl, etc.), salicylic acid derivatives (octyl salicylate, phenyl salicylate, homomenthyl salicylate, dipropylene glycol salicylate, ethylene glycol salicylate, myristyl salicylate, Methyl salicylate, etc.), anthranilic acid derivatives (methyl anthranilate, etc.), urocanic acid derivatives (urocanic acid, ethyl urocanate, etc.), coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives , Camphor derivative, furan derivative, pyrone derivative, nucleic acid derivative, allantoin derivative, nicotinic acid derivative, vitamin B6 derivative Body, umbelliferone, esculin, benzyl cinnamate, sinoxate, oxybenzone, dioxybenzone, octabenzone, thrisobenzone, benzoresorcinol, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine, neoheliopan, escalol, zinc oxide, talc, kaolin etc.

(19) Whitening agent Paraaminobenzoic acid derivative, salicylic acid derivative, anthranilic acid derivative, coumarin derivative, amino acid compound, benzotriazole derivative, tetrazole derivative, imidazoline derivative, pyrimidine derivative, dioxane derivative, camphor derivative, furan derivative, pyrone derivative, Nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, vitamin C or derivatives thereof (vitamin C phosphate magnesium salt, vitamin C glucoside, etc.), vitamin E or derivatives thereof, kojic acid or derivatives thereof, oxybenzone, benzophenone, arbutin, guaiazulene, Shikonin, baicalin, baicalein, berberine, placenta extract, ellagic acid, lucinol, etc.

(20) Tyrosinase activity inhibitor Vitamin C or a derivative thereof (vitamin C phosphate magnesium salt, vitamin C glucoside, etc.), hydroquinone or a derivative thereof (hydroquinone benzyl ether, etc.), kojic acid or a derivative thereof, vitamin E or a derivative thereof, N-acetyltyrosine or derivatives thereof, glutathione, hydrogen peroxide, zinc peroxide, placenta extract, ellagic acid, arbutin, lucinol, silk extract, plant extract (camille, mulberry, gardenia, pearl oyster, clam, clam, mugwort, honeysuckle) , Kihada, dokudami, matsuhod, pearl barley, mussel, hops, hawthorn, eucalyptus, yarrow, altea, keihi, mankaishi, hamamelis, yamagwa, lifelong grass, bellflower, toshishi, zetsugo, gyu, mao, senkyu, dod Tsu, Psycho, storm, littoralis, Scutellaria, peony bark, cranesbill, kudzu root, licorice, Fushi aloe, Cimicifuga, safflower, green tea, black tea, Ali elixir), and the like.

(21) Melanin pigment reduction / decomposition substance Phenylmercury hexachlorophene, mercuric oxide, mercuric chloride, hydrogen peroxide, zinc peroxide, hydroquinone or its derivative (hydroquinone benzyl ether).

(22) Turnover promoting action / cell activator hydroquinone, lactic acid bacteria extract, placenta extract, ganoderma extract, vitamin A, vitamin E, allantoin, spleen extract, thymus extract, yeast extract, fermented milk extract, plant extract (aloe, Ogon, Japanese horsetail, Gentian, Burdock, Shikon, Carrot, Camelis, Hop, Yokuinin, Odori, Semburi, Japanese cypress, Japanese red snapper, Achacha, Hypericum, Cucumber, Necklace, Rosemary, Parsley).

(23) Astringents Succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc paraphenolsulfonate, potassium aluminum sulfate, resorcin, ferric chloride, tannic acid (including catechin compounds) and the like.

(24) Active oxygen scavenger SOD, catalase, glutathione peroxidase and the like.

(25) Antioxidants Vitamin C or salts thereof, stearic acid ester, vitamin E or derivatives thereof, nordihydrogua cetelenic acid, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), hydroxytyrosol, parahydroxyanisole , Propyl gallate, sesamol, sesamorin, gossypol, propolis, etc.

(26) Lipid peroxide production inhibitor β-carotene, plant extract (sesame culture cell, hamcha, hypericum, hamamelis, clove, melissa, birch, birch, salvia, rosemary, minamitenji, jitsu, ginkgo, green tea).

(27) Anti-inflammatory agent Ictamol, indomethacin, kaolin, salicylic acid, sodium salicylate, methyl salicylate, acetylsalicylic acid, diphenhydramine hydrochloride, d-camphor, dl-camphor, hydrocortisone, guaiazulene, camazulene, chlorpheniramine maleate, glycyrrhizic acid or its Salt, glycyrrhetinic acid or a salt thereof, licorice extract, sicon extract, age extract, propolis, etc.

(28) Antibacterial / bactericidal / disinfectant Acrinol, sulfur, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin or hydrolyzate thereof, alkyldiaminoethylglycine chloride solution, triclosan, sodium hypochlorite, chloramine T, Sarashi powder, iodine compound, iodoform, sorbic acid or its salt, propionic acid or its salt, salicylic acid, dehydroacetic acid, parahydroxybenzoic acid esters, undecylenic acid, thiamine lauryl sulfate, thiamine lauryl nitrate, phenol, cresol, p -Chlorophenol, p-chloro-m-xylenol, p-chloro-m-cresol, thymol, phenethyl alcohol, O-phenylphenol, Irgasan CH3565, halocarban, hexachlorophene, chlorohexidine, ester Tanol, methanol, isopropyl alcohol, benzyl alcohol, ethylene glycol, propylene glycol, 2-phenoxyethanol, 1,2-pentanediol, zinc pyridione, chlorobutanol, isopropylmethylphenol, nonionic surfactant (polyoxyethylene lauryl ether, Polyoxyethylene nonyl phenyl ether, polyoxyethylene octyl phenyl ether, etc.), amphoteric surfactant, anionic surfactant (sodium lauryl sulfate, lauroyl sarcosine potassium, etc.), cationic surfactant (cetyltrimethylammonium bromide, benzalkco chloride) Nium, benzethonium chloride, methyl rosaniline chloride), formaldehyde, hexamine, brilliant green, malachite green, crystal bio Tsu DOO, Jamaru photosensitive No. 101-containing, photosensitizer No. 201, photosensitizer No. 401, N- long chain acyl basic amino acid derivative and its acid shark salts, zinc oxide, hinokitiol, Sophora root, propolis, and the like.

(29) Moisturizer Glycerin, propylene glycol, 1,3-butylene glycol, hyaluronic acid or its salt, polyethylene glycol, chondroitin sulfate or its salt, water-soluble chitin or its derivative or chitosan derivative, pyrrolidone carboxylic acid or its salt, lactic acid Sodium, mini Sasanishiki extract, natto metabolite, natto extract, loofah water, birch (white birch) or red pine sap

(30) Elastase activity inhibitor diisopropyl fluorophosphate, plant extract (eg, gongoid, hypericum, clara, mulberry leaves, keihi, genokosho, comfrey, salvia, elderberry, bodaiju, button pie), seaweed extract and the like.

(31) Hair preparations Selenium disulfide, alkylisoquinolinium bromide solution, zinc pyrithione, biphenamine, thianthol, castari tincture, pepper tincture, pepper tincture, quinine hydrochloride, strong ammonia water, potassium bromate, sodium bromate, thio Glycolic acid and the like.

(32) Antiandrogens Follicular hormones (estrone, estradiol, ethinyl estradiol, etc.), isoflavones, oxendrone, etc.

(33) Peripheral vascular blood flow promoter Vitamin E or derivatives thereof, assembly extract, garlic extract, carrot extract, aloe extract, gentian extract, toki extract, cephalanthin, carpronium chloride, minoxidil and the like.

(34) Stimulants Pepper tincture, nonyl acid vanillamide, cantalis tincture, ginger tincture, peppermint oil, l-menthol, camphor, benzyl nicotinate and the like.

(35) Metabolic activator Photosensitive element 301, hinokitiol, pantothenic acid or derivatives thereof, allantoin, placenta extract, biotin, pentadecanoic acid glyceride and the like.

(36) Antiseborrheic agent Pyridoxine or a derivative thereof, sulfur, vitamin B6 and the like.

(37) Keratolytic agent Resorcin, salicylic acid, lactic acid, urea and the like.

(38) Oxidizing agent Hydrogen peroxide water, sodium persulfate, ammonium persulfate, sodium perborate, urea peroxide, sodium percarbonate, sodium tripolyphosphate, sodium bromate, potassium bromate, sodium pyrophosphate, Sodium orthophosphate, sodium silicate hydrogen peroxide adduct, sodium sulfate hydrogen peroxide adduct, sodium chloride hydrogen peroxide adduct, β-tyrosinase enzyme solution, mushroom extract, etc.

(39) Hair remover Inorganic reducing agents such as strontium sulfate, sodium sulfide, barium sulfide, calcium sulfide, thioglycolic acid or its salts (calcium thioglycolate, sodium thioglycolate, lithium thioglycolate, magnesium thioglycolate) Strontium thioglycolate) and the like.

(40) Hair swelling agents such as ethanolamine, urea and guanidine.

(41) Dye agent
5-aminoorthocresol, 2-amino-4-nitrophenol, 2-amino-5-nitrophenol, 1-amino-4-methylaminoanthraquinone, 3,3'-iminodiphenol, 2,4-diaminophenoxyethanol hydrochloride 2,4-diaminophenol hydrochloride, toluene-2,5-diamine hydrochloride, nitroparaphenylenediamine hydrochloride, paraphenylenediamine hydrochloride, N-phenylparaphenylenediamine hydrochloride, metaphenylenediamine hydrochloride, orthoaminophenol, N-phenyl acetate Paraphenylenediamine, 1,4-diaminoanthraquinone, 2,6-diaminopyridine, 1,5-dihydroxynaphthalene, toluene-2,5-diamine, toluene-3,4-diamine, nitroparaphenylenediamine, paraaminophenol, para Nitroorthophenylenediamine, paraphenylenediamine, paramethylamino Phenol, picramic acid, sodium picramate, N, N'-bis (4-aminophenyl) -2,5-diamino-1,4-quinonediimine, 5- (2-hydroxyethylamino) -2-methylphenol, N -Phenylparaphenylenediamine, metaaminophenol, metaphenylenediamine, 5-aminoorthocresol sulfate, 2-amino-5-nitrophenol sulfate, orthoaminophenol sulfate, orthochloroparaphenylenediamine sulfate, 4,4'-diamino sulfate Diphenylamine, 2,4-diaminophenol sulfate, toluene-2,5-diamine sulfate, nitroparaphenylenediamine sulfate, paraaminophenol sulfate, paranitroorthophenylenediamine sulfate, paranitrometaphenylenediamine sulfate, paraphenylenediamine sulfate, parasulfate sulfate Methylaminophenol, metaaminosulfate Diol, metaphenylenediamine sulfate, catechol, diphenylamine, α-naphthol, hydroquinone, pyrogallol, phloroglucin, gallic acid, resorcin, tannic acid, 2-hydroxy-5-nitro-2 ', 4'-diaminoazobenzene-5'-sulfone Sodium acid, hematein, etc.

(42) Fragrance Natural animal fragrance such as musk, civet, castorium, ambergris, anise essential oil, angelica essential oil, ylang ylang essential oil, iris essential oil, fennel essential oil, orange essential oil, cananga essential oil, caraway essential oil, cardamom essential oil, guayakwood essential oil, Cumin essential oil, black letter essential oil, cinnamon essential oil, cinnamon essential oil, geranium essential oil, copaiba balsam essential oil, coriandel essential oil, perilla essential oil, cedarwood essential oil, citronella essential oil, jasmine essential oil, gingergrass essential oil, cedar essential oil, spearmint essential oil, western peppermint essential oil, Otsuka perfume essential oil, tuberose essential oil, clove essential oil, orange flower essential oil, winter green essential oil, trout balsam essential oil, buttery essential oil, rose essential oil, palmarosa essential oil, persimmon essential oil, hiba essential oil, sandalwood essential oil, petit gren essential oil, bay essential oil, vetiva essential oil, bergamot Spirit , Peru balsam essential oil, boad rose essential oil, melamine essential oil, mandarin essential oil, eucalyptus essential oil, lime essential oil, lavender essential oil, linaloe essential oil, lemongrass essential oil, lemon essential oil, rosemary essential oil, Japanese mint essential oil, and other synthetic flavors Fragrance etc.

(43) Dye and Colorant Red Cabbage Dye, Red Rice Dye, Akane Dye, Anato Dye, Ikumi Dye, Turmeric Dye, Enju Dye, Krill Dye, Amber Dye, Caramel, Gold, Silver, Gardenia Dye, Corn Dye, Onion Dye , Tamarind pigment, spirulina pigment, buckwheat whole plant pigment, cherry pigment, laver pigment, hibiscus pigment, grape juice pigment, marigold pigment, purple potato pigment, purple yam pigment, lac pigment, rutin etc.

(44) Sweeteners Sugar, sweet tea, fructose, arabinose, galactose, xylose, stevia, mannose, maltose, honey, glucose, miraculin, monelin, licorice extract and the like.

(45) Nutrient enhancer Shell calcined calcium, cyanocobalamin, yeast, wheat germ, egg yolk powder, hemicellulose, heme iron and the like.

(46) Dairy products Milk, cheese, fresh cream, butter, margarine, powdered milk, whey, condensed milk, etc.

(47) Others Hormones, sequestering agents, pH adjusters, chelating agents, antiseptic and antifungal agents, cooling agents, stabilizers, emulsifiers, animal and vegetable proteins and their degradation products, animal and vegetable polysaccharides And its degradation products, animal and plant glycoproteins and their degradation products, blood flow promoters, anti-inflammatory agents, anti-inflammatory agents, anti-allergic agents, wound treatment agents, foam increasing agents, thickeners, enzymes, purified water (electronic Water, small clustering, etc.), oral preparations, deodorants / deodorants, bittering agents, seasonings, etc. are raised, and in combination with these, the effects of the present invention or other cosmetic effects are added Or a synergistic improvement can be expected.

(Manufacture of extracts from grape fruit pressing residue)
The fruit pressing residue (300 to 600 g) of various grapes was subjected to immersion extraction at room temperature to warming with addition of a solvent (1 to 2 kg), followed by suction filtration to obtain an extract (about 1 to 2 kg). By this operation, extracts (samples 1 to 5) from grape fruit pressing residues as shown in Table 1 were obtained. Moreover, regarding Chardonnay fruit pressing residue, 1,3-BG (sample 1, 6-8), water (sample 9), or ethanol (sample 10-13) was used as a solvent, and was made to correspond to each solvent concentration. Various extracts were obtained. Moreover, regarding the Niagara fruit pressing residue, 1,3-BG (sample 2, 14-16) or water (sample 17), or ethanol (sample 18-21) was used as a solvent, and it was made to respond | correspond to each solvent density | concentration. Various extracts were obtained.

(ABCA12 gene expression promoting effect test)
Using the quantitative PCR (polymerase chain reaction method) method, the expression promoting effect of the ABCA12 gene was evaluated.
"Test method and evaluation method"
Human epidermal cells HaCaT were seeded on a culture plate and cultured in a medium on DMEM containing 5% FBS until subconfluent at 37 ° C. in a 5% CO ₂ atmosphere. Next, the medium was replaced with a DMEM medium containing 1% FBS, and after culturing for 24 hours, each sample (Table 1) produced in the above Example was added to the medium and cultured for 2 hours. Thereafter, the medium is replaced with 1% FBS-containing DMEM medium, and further cultured for 6 hours. The cells are extracted using an RNA extraction kit (QIAGEN), and PrimeScript RT reagent Kit (Takara Bio) is used with the obtained RNA as a template. Was used to synthesize cDNA. As a control (comparative control), a considerable amount of a solution equivalent to the solvent of the sample was used. Using this cDNA, the expression level of the gene was measured by a quantitative PCR method (polymerase chain reaction method). SYBR Premix Ex Taq (Takara Bio Inc.) was used for the quantitative PCR method. As an internal standard, the expression level of RPS18, which is a housekeeping gene, was quantified, and the relative expression level ratio relative to RPS18 was calculated as the ABCA12 gene relative expression level ratio. Commercially available ABCA12 and RPS18 primers (QuantiTect Primer: Qiagen or Perfect Real Time Primer: Takara Bio Inc.) were used as PCR primers.

(Test results)
The ratio of the relative expression level of ABCA12 gene due to the addition of extracts from various grape fruit press residues was as shown in FIG. When the expression level in a control (comparative control) 30% 1,3-BG aqueous solution is 1.0, Chardonnay is 2.817, Niagara is 1.976, Pinot Noir is 1.161, Merlot is 1. 289 and Cabernet Franc were 1.088. Among the extracts from grape fruit press residue, the expression level of ABCA12 gene was significantly increased especially in Chardonnay, and the highest ABCA12 gene expression promoting effect was observed. In addition, among the extracts from other grape fruit pressing residues, the expression level of ABCA12 gene was increased in Niagara, and the highest ABCA12 gene expression promoting effect was observed after Chardonnay. In addition, the expression promoting effect of ABCA12 gene was also observed in Pinot Noir, Merlot and Cabernet Franc, respectively, but the increase was slight.

  Moreover, when the extract from grape fruit press residue was Chardonnay, the ABCA12 gene relative expression ratio by adding the extract extracted with various concentrations of 1,3-BG aqueous solution was as shown in FIG. Chardonnay 30% 1,3-BG extract is 2.199, Chardonnay 50% 1,3-BG extraction when the expression level in 90% 1,3-BG aqueous solution of control (comparative control) is 1.0 The product was 1.664, Chardonnay 70% 1,3-BG% extract was 1.000, Chardonnay 90% 1,3-BG extract was 1.030. Among the 1,3-BG aqueous extracts, especially the Chardonnay 30% 1,3-BG extract and 50% 1,3-BG extract, the expression level of ABCA12 is remarkably increased, and high ABCA12 gene expression is promoted. The effect was recognized. Therefore, when extracting with 1, 3-BG aqueous solution, extracting with the density | concentration of 30-50% was considered to be the optimal conditions.

  Furthermore, when the extract from grape fruit pressing residue was Chardonnay, the ABCA12 gene expression relative quantity ratio by adding the extract extracted with various concentrations of aqueous ethanol solution was as shown in FIG. When the expression level in 90% ethanol aqueous solution of control (comparative control) is 1.0, Chardonnay water extract is 1.040, Chardonnay 30% ethanol extract is 2.295, Chardonnay 50% ethanol extract is 3 500, Chardonnay 70% ethanol extract 2.426, Chardonnay 90% ethanol extract 2.217. Among the aqueous ethanol extracts, particularly the Chardonnay 50% ethanol extract, the expression level of the ABCA12 gene was remarkably increased. However, the ABCA12 gene expression promoting effect was also observed in the other aqueous ethanol extracts. Therefore, in the case of extraction with an aqueous ethanol solution, it was considered that extraction at a concentration of 30 to 90% was the optimum condition.

  Moreover, when the extract from grape fruit press residue was made into Niagara, the ABCA12 gene relative expression ratio by the extract addition extracted with various density | concentrations 1, 3-BG aqueous solution was as showing in FIG. Niagara 30% 1,3-BG extract is 1.758, Niagara 50% 1,3-BG extraction when the expression level in 90% 1,3-BG aqueous solution of control (comparative control) is 1.0 The product was 1.457, Niagara 70% 1,3-BG% extract was 1.18543, Niagara 90% 1,3-BG extract was 1.085. Among the 1,3-BG aqueous extracts, the expression level of ABCA12 is remarkably increased, especially in Niagara 30% 1,3-BG extract and 50% 1,3-BG extract, and high ABCA12 gene expression promotion The effect was recognized. Therefore, when extracting with 1, 3-BG aqueous solution, extracting with the density | concentration of 30-50% was considered to be the optimal conditions.

  Furthermore, when the extract from the grape fruit pressing residue was Niagara, the ABCA12 gene expression relative amount ratio by adding the extract extracted with various concentrations of aqueous ethanol was as shown in FIG. When the expression level in the 90% ethanol aqueous solution of the control (comparative control) is 1.0, the Niagara water extract is 0.986, the Niagara 30% ethanol extract is 2.057, and the Niagara 50% ethanol extract is 2 862, Niagara 70% ethanol extract 1.865, Niagara 90% ethanol extract 2.000. Among the aqueous ethanol extracts, the expression level of ABCA12 gene was remarkably increased particularly in the Niagara 50% ethanol extract, but the ABCA12 gene expression promoting effect was also observed in the other aqueous ethanol extracts. Therefore, in the case of extraction with an aqueous ethanol solution, it was considered that extraction at a concentration of 30 to 90% was the optimum condition.

  Therefore, the extract from the grape fruit press residue according to the present invention, in particular, Chardonnay or Niagara is useful as an excellent ABCA12 gene expression promoter. In addition, extraction of those extraction solutions with 30-50% 1,3-BG or 30-90% ethanol aqueous solution is a condition for obtaining the ABCA12 gene expression promoter that is most effective.

(Skin primary irritation test)
Samples 1 to 9 or Samples 14 to 17 produced in the above examples were prepared so that the dry solid content concentration was 2.0% by weight, and the Japanese white rabbit (female, 3 per group, shaved back) , About 2.1 kg body weight). Evaluation was performed using erythema and edema as an index based on the criteria for Draise 24, 48, and 72 hours after application. As a result, it was judged that no erythema and edema were observed in all animals in each sample, and there was no problem with respect to primary skin irritation.

(Cumulative skin irritation test)
Samples 1 to 9 and Samples 14 to 17 produced in the above examples were prepared so that the dry solids concentration was 2.0% by weight, and the Hartley guinea pig (female, 3 animals per group, body weight) with the back shaved. (Approx. 320 g), 0.5 mL / animal was applied once a day, 5 times a week. Application was performed over 2 weeks and shaving was performed on the last application day of each week. Evaluation was performed using erythema and edema as indices based on the criteria for Draise on the day after each application and the day after the last application. As a result, it was judged that no erythema and edema were observed for 2 weeks in all the animals in all the animals, and there was no problem regarding the cumulative skin irritation.

(Acute toxicity test)
Samples 9, 13, 17, and 21 prepared in the above example were dried and ddy mice (male and female, 5 mice per group, 5 weeks old) fasted for 4 hours before the test, respectively. 000 mg / kg was orally administered, and the onset and degree of toxic symptoms were observed over time. As a result, no abnormality was observed in all mice for 14 days, and no abnormalities were found in the anatomy. Therefore, LD50 was 2,000 mg / kg or more, which was judged to be safe.

Production examples of various dosage forms of foods and drinks containing the ABCA12 gene expression promoter of the present invention (tablet type confectionery) (parts by weight)
1. Powdered sugar 87
2. Lactose 2
3. Vitamin C 3
4). Citric acid 1.5
5. Gelatin 1% aqueous solution 4
6). Sample 13 produced in the example, or dry powder of sample 21 1
7). Sucrose fatty acid ester 1
8). Powdered strawberry flavor 0.5
Were mixed uniformly and tableted according to a normal tablet production method to obtain a tablet-type confectionery.

(Tablet) (Part by weight)
1. Cornstarch 30
2. Microcrystalline cellulose 30
3. Carboxymethylcellulose calcium 24
4). Polyvinylpyrrolidone 10
5. Sample 9 produced in Example, or dry powder of sample 17 1
6). Talc 5
Were mixed uniformly and tableted according to a normal tablet production method to obtain a tablet.

(Capsule tablets) (Weight)
1. Cornstarch 100mg
2. Lactose 100mg
3. Processed garlic extract (powder) 10mg
4). Magnesium stearate 2mg
Were mixed uniformly and filled into gelatin capsules in accordance with a conventional method for producing capsules to obtain capsules.

(Tablet health food) (Parts by weight)
1. Salmon nasal cartilage extract containing proteoglycan 4
(Proteoglycan F, manufactured by Ichimaru Falcos)
2. Chondroitin sulfate 2
3. Hyaluronic acid 0.5
4). N-acetylglucosamine 40
5. Collagen extract powder 7.5
6). Sample 10 produced in the example, or dry powder of sample 18 2
7). Crystalline cellulose 9
8). Sucrose fatty acid ester 3
9. Fine silicon oxide 2
10. Maltitol 30
Were mixed uniformly and tableted according to a normal tablet production method to obtain a tablet-type health food.

(Cookie confectionery) (Parts by weight)
1. Light flour 35
2. Whole egg 10
3. Concentrated paste of sample 11 or sample 19 produced in the example 2
4). Butter 20
5. Sugar 12
6). Salt 10
7). Baking powder 0.3
8). Water 10.7
Were uniformly mixed and the cookies were baked according to a conventional method.

(飴) (Weight)
1. Minamata 500g
2. 500g sugar
Is mixed and heated at 120 ° C. under reduced pressure (−500 mmHg), and then cooled to 90 ° C. to this,
3. Sample 11 produced in Example, or concentrated solution of sample 19 5 g
4). 30g of kombu pulverized powder
5. Stevia extract 20g
6). Citric acid 10g
7). Fragrance 1.5mL
Was added and kneaded sufficiently, and this was punched and molded into a circle having a diameter of 15 mm and a thickness of 8 mm to produce a bag.

(Tomato juice drink) (Weight)
1. Commercial tomato juice 1kg
2. 0.3 g of the concentrated paste of Sample 9 or Sample 17 produced in the example
Were mixed uniformly to obtain a tomato juice drink.

(Vegetable juice drink) (weight)
1. 1kg of commercially available vegetable juice
2. 0.3 g of dry powder of sample 13 or sample 21 produced in the example
Were mixed uniformly to obtain a vegetable juice drink.

(Health-oriented beverage) (Weight)
1. 0.2 g of dry powder of sample 9 or sample 17 produced in the example
2. Erythritol 50g
3. Vitamin C 1g
4). Artificial sweetener 0.06g
5. Fragrance 1.2g
The solution was stirred and dissolved in 1 L of water at a liquid temperature of 70 ° C., adjusted to pH 3.0 with citric acid, sterilized using an ultrafilter, filled into a bottle, sterilized with a pasteurizer to produce a beverage.

(Soft drink) (Part by weight)
1. Fructose dextrose solution 20.0
2. Liquid yogurt 30.0
2. Emulsifier 0.5
3. Sodium hyaluronate (molecular weight 50,000-150,000) 0.1
4). Concentrated paste of sample 10 or sample 18 produced in the example 1.0
5. Perfume appropriate amount 5. The remaining amount of purified water 100 was uniformly mixed, and a soft drink was obtained according to a conventional method.

Example of production of seasoning blended with ABCA12 gene expression promoter of the present invention (salt / pepper seasoning) (weight)
1. Commercial salt and pepper seasoning 1kg
2. 50 g of dry powder of sample 13 or sample 21 produced in the example
Were mixed uniformly to obtain a salt / pepper seasoning.

Example of production of external preparation containing ABCA12 gene expression promoter of the present invention (whitening lotion) (parts by weight)
1. Sorbit 2
2. 1,3-butylene glycol 5
3. Polyoxyethylene oleyl ether (25E.O.) 2
4). Ethanol 20
5. Ascorbic acid-2-glucoside 0.3
6). Sample 1 or Sample 2 manufactured in the example 2
7). 30% green tea-ethanol extract (solid content 1.0%) 8
8). 8. pH adjuster Suitable amount to make pH 5-6 Preservative (phenoxyethanol) Appropriate amount10. Residue with 100 purified water

(Emollient emulsion) (parts by weight)
1. Squalane 3
2. Vaseline 1
3. Stearyl alcohol 0.3
4). Sorbitan monostearate 1.5
5. Polyoxyethylene (20) sorbitan monooleate 3
6.1,3-Butylene glycol 10
7). Sample 6 manufactured in Example, or Sample 14 1
8). Hydrolyzed collagen 1% aqueous solution 1.0
(Ichimaru Falcos, Falconix CTP)
9. Chamomile flower head 70% 1,3-BG extract (solid content 0.8%) 5
10. Proteoglycan solution 0.2
(Ichimaru Falcos Proteoglycan IPC)
11. Sodium hyaluronate 0.0005
12 Preservative (methylparaben) appropriate amount13. Residue with 100 purified water

(Hair shampoo) (parts by weight)
1. Lauryl sulfate triethanolamine 5
2. Sodium polyoxyethylene lauryl ether sulfate 12
3.1,3-BG 4
4). Lauric acid diethanolamide 2
5. 2-Phenylchromone 0.01
6). Sample 1 or Sample 2 manufactured in Example 1
7). Arginine or its salt 0.2
8). Preservative (ethyl paraben) Appropriate amount 9. Residue with 100 purified water

(Granule bath preparation) (Parts by weight)
1. Sodium bicarbonate 60
2. Anhydrous sodium sulfate 32
3. Borax 5
4). Sample 13 produced in Example, or dry powder of Sample 21 3
Were mixed uniformly to obtain a granule bath preparation.

  The extract from the grape fruit pressing residue according to the present invention has an excellent ABCA12 gene expression promoting effect. So far, no preparation has been found that promotes the direct expression and synthesis of ABCA12 in extracts from water, hydrophilic 1,3-butylene glycol (BG), ethanol, or mixtures thereof. It is extremely useful and can be applied in a wide range of industries. Therefore, the ABCA12 gene expression promoter according to the present invention can be used not only for pharmaceuticals and foods (including beauty and health-oriented foods and drinks) but also for external preparations such as beverages and cosmetics.

Claims (2)

ABCA12 gene expression promoter containing as an active ingredient an extract from grape fruit press residue The ABCA12 gene expression promoter according to claim 1, wherein the grape is Chardonnay or Niagara.

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