JPH09323915A - Melanin generation inhibitor consisting of n-acetylthyrosine derivative as active ingredient and application of the same to skin preparation for external use and bath agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a melanin generation inhibitor useful as a skin preparation for external use or a bath agent by using a specific compound having an excellent melanin generation inhibiting effect as an active ingredient. SOLUTION: This melanin generated inhibitor consists of an N- acertylthyrosine derivative selected from among four compounds of the formula, i.e., N-acetylthyrosin for which R of the formula is H, N-acetylthyrosine sodium of which R is Na, N-acetylthyrosine potassium for which R is K and N- acetylthyrosine ethyl ester for witch R is C2 H5 , as an active ingredient. The melanin generation inhibitor can perform a prevention and an improvement to skin troubles such as a pigmentation such as stains and freckles, and a dyschromatosis. The blending amount of the N-acetylthrosine derivative is approximately 0.005-3.0%, and approximately 0.007-2.0% is especially preferable. The melanin generation inhibitor has a high safety, and excellent skin beautifying effects such as a skin conditioning effect and a moisture keeping effect, are obtained.

Description

Detailed Description of the Invention

The present invention provides a novel melanin containing, as an active ingredient, one or more compounds selected from the N-acetyltyrosine derivatives represented by the following structural formula (Formula 1). The present invention relates to a production inhibitor and a skin external preparation or bath preparation containing the same.

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[0002]

TECHNICAL FIELD The skin external preparation or bath preparation as referred to in the present invention is an external preparation for the purpose of preventing or improving pigmentation such as spots, freckles, and skin troubles such as pigmentation disorders. Means general. Specifically, liquids, emulsions, creams, ointments, gels, powders, granules, solids, or foams, 1) topical drugs, 2) quasi drugs, 3) topical or There are skin cosmetics for the whole body, 4) bath agents to be used by throwing in bath water.

[0003]

2. Description of the Related Art Pigmentation of the skin such as liver spots (spots), freckles (freckles) and senile mollusks is a condition often observed by exposure to ultraviolet rays, cosmetic rashes, contact dermatitis, etc. , Is one of the major worries for women. The melanin pigments caused by these are organelles called premelanosomes formed in the cytoplasm of melanocytes distributed in the epidermal basal cell layer of skin,
It is generated under a certain genetically defined active order. Normally, the mature melanosomes filled with this melanin pigment reach the body surface along with the keratinization process, and finally they are exfoliated and excreted outside the body.However, due to various factors, the balance between the production and excretion of melanosomes is high. It has been clarified that a collapse occurs, and when it is excessively accumulated in epidermal cells, the symptoms as described above appear. By the way, until now, many researchers have developed an active ingredient applicable as an external preparation for the prevention or treatment of such pigment abnormality, and some have already been put to practical use.

When these are systematically summarized, the following three factors are considered to be the main causes of pigmentation. (1) Formation of melanin pigment exceeding the normal level (2) Deposition of melanin pigment on tissue cells (3) Decrease in melanin pigment elimination (excretion) function And, as a countermeasure against (1), blocking and absorption of ultraviolet rays , Suppression of active oxygen production, suppression of lipid peroxide production, Tyro
Inhibition of sinase activity (suppression of melanin pigment production), etc., and in response to (2) and (3), it exerts actions and effects such as reduction / degradation of melanin pigment, promotion of turnover, and repair of damaged cells. Ingredients and the like have been searched for, and for example, applied to daily-used cosmetics and the like for consideration. Table 1 is an example of the effective ingredients that have been proposed so far.

[Table 1]

[0005]

As shown in Table 1, many components effective for preventing and improving pigmentation have been proposed so far, but among them, the effect is extremely strong and permanent. It contains many whitening ingredients that may cause various decolorizing effects, those that are effective against each but exhibit cytotoxicity, and those that are safe but were not expected in practice as effective as in the test system. Was there. Also,
Although it is safe and has some effectiveness, it has extremely poor stability, or has problems with odor, color tone, solubility, etc. Some of them have drawbacks such that they cannot be applied, and the actual number of practically active ingredients is very limited.

The inventors of the present invention have conducted extensive studies with the aim of developing a new cosmetic ingredient which is highly effective and practical. As a result, they have found that the above-mentioned N-acetyltyrosine derivative is an extremely useful component that has a melanin production inhibitory action and at the same time can solve the above problems. Then, by applying the above-mentioned components to external preparations for skin and bath agents, it is effective in preventing and improving spots, freckles, etc., as well as preventing and improving rough skin and dryness, and smoothing the texture of the skin (skin The inventors have completed the present invention, knowing that an excellent skin-improving effect such as improvement of quality itself and moisturizing can be obtained.

[0007]

The present invention comprises the following two inventions. 1. Melanin production inhibitor containing, as an active ingredient, one or more N-acetyltyrosine derivatives selected from N-acetyltyrosine, N-acetyltyrosine sodium, N-acetyltyrosine potassium and N-acetyltyrosine ethyl ester. . 2. A skin external preparation or bath preparation containing the above-mentioned melanin production inhibitor containing an N-acetyltyrosine derivative as an active ingredient.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The active ingredient of the present invention: a melanin production inhibitor containing an N-acetyltyrosine derivative is not only dried powder but also dissolved in a solvent such as water, alcohol, glycol or the like, an emulsion (emulsion). Shape) etc.

Further, the skin external preparation or bath preparation containing the melanin production inhibitor containing the N-acetyltyrosine derivative according to the present invention is produced by formulating it with a base or additive usually used in cosmetics. It At that time, the compounding amount is usually about 0.005 to 3.0% as an N-acetyltyrosine derivative. If it is 0.005% or less, a sufficient effect cannot be obtained, and if it exceeds 3.0%, the effect corresponding to the concentration cannot be enhanced. Considering the effect and safety of the examples described below, 0.007
The most preferable range is about 2.0%. In the case of a bath agent, it may be added to 200 to 300 liters of bath water so as to give the same concentration and the formulation may be considered.

[0010]

[Example] Melanin production inhibitory effect [Preparation of sample] -N-acetyl tyrosine solution-N-acetyl tyrosine sodium solution-N-acetyl tyrosine potassium solution-N-acetyl tyrosine ethyl ester solution-L-tyrosine solution-N-acetyl Tyrosine derivative + L-tyrosine mixed solution

[Reaction solution] Sample 1.0 mL McIlvaine buffer solution (pH 6.5) 1.0 mL Purified water 0.9 mL Tyrosinase solution (2,500 u / mL) 0.1 mL

[Method] The reaction solution was stored at 37 ° C. and observed over time.

[Results] The results are shown in the following table (Table 2). When the substrate is only L-tyrosine, melanin (black precipitate) is formed 5 hours after the start of the test. However, it was confirmed that the presence of an N-acetyltyrosine derivative in this clearly suppressed the production of melanin.

[Table 2]

[0014]

[Examples] Safety test 1) Primary skin irritation test A rabbit was prepared by preparing a solution sample in which each N-acetyltyrosine derivative used in the present invention was dissolved in an amount of 3%, and the back of the rabbit was dehaired (3 mice per group, It was applied to the skin having a body weight of about 3,800 g). The evaluation was performed 24, 48, and 72 hours after application using the erythema and edema as indices by the primary irritation scoring method. As a result, in each sample, all the animals did not show any erythema and edema, and were judged as negative.

2) Skin cumulative irritation test A solution sample was prepared by dissolving each N-acetyltyrosine derivative used in the present invention in an amount of 3%, and the flank of the flank was removed (2
× 4 cm ² ) Hartley guinea pig (female, 5 per group)
(1 animal, body weight 320g) once a day, 5 times a week, 0.
5 mL / per animal was applied. Application was performed over 4 weeks and hair removal was performed on the last application day of each week. The judgment was made on the day following the last day of each week by using primary irritation scoring method with erythema and edema as indices. As a result, in all the samples, erythema and edema were not observed in all animals for 1 to 4 weeks after the application, and it was determined to be negative.

3) Acute toxicity test Each N-acetyltyrosine derivative used in the present invention was orally administered to ddy mice (5 mice per group, body weight 30 g) fasted for 4 hours before the test in an amount of 2,000 mg / kg. , The occurrence of toxic symptoms, the degree, etc. were observed over time. As a result, in each sample, no abnormality was observed in all the mice for 14 days, and there was no abnormality in the dissection result. LD ₅₀ was determined to be 2,000 mg / kg or more.

[0017]

[Examples] Application to various preparations When various preparations are produced by applying the melanin production inhibitor according to the present invention, pharmaceuticals, quasi-drugs, cosmetics, bath preparations, food and drink as shown below are used. From various components and additives that are usually used in products,
Any suitable one can be selected and used in combination.

(1) Various fats and oils Avocado oil, almond oil, fennel oil, perilla oil,
Olive oil, orange oil, orange lafa oil, sesame oil, cocoa butter, chamomile oil, carrot oil, cucumber oil, tallow fatty acid, kukui nut oil, safflower oil, 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, oak, coconut oil, beef tallow, lard, milk fat, or hydrogenated products of these fats (hardened oil, etc.) Such.

(2) Waxes Beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax,
Montan wax, shellac wax, etc.

(3) Mineral oil Liquid paraffin, petrolatum, paraffin, ozokeride, ceresin, microcristan wax, squalene, squalane, pristane, etc.

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

(5) Alcohols ethanol, isopropyl alcohol, lauryl alcohol,
Natural alcohols such as cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, and phytosterol; and synthetic alcohols such as 2-hexyldecanol, isostearyl alcohol, and 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, glycerin, pentaerythritol, sorbitol, mannitol, etc.

(7) Esters Isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, cetyl lactate, Myristyl lactate, diethyl phthalate, dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate, etc.

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

(9) Gum, sugar and water-soluble polymer compound gum arabic, benzoin gum, dammar gum, guaiac butter, Irish moss, karaya gum, tragacanth gum,
Carob gum, quinseed, agar, casein, lactose,
Fructose, sucrose and its esters, trehalose and its derivatives, dextrin, gelatin, pectin, starch, carrageenan, carboxymethyl chitin or hydroxyalkyl (C ₂ -C ₄ ) oxide to which alkylene (C ₂ -C ₄ ) oxide such as ethylene oxide is added _{2 to} C ₄ ) chitin or chitosan, low molecular weight chitin or chitosan, chitosan salt, sulfated chitin or chitosan, phosphorylated chitin or chitosan, alginic acid and its salt, hyaluronic acid and its salt, chondroitin sulfate and its salt, heparin, ethyl cellulose , Methylcellulose, carboxymethylcellulose, carboxyethylcellulose, sodium carboxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, nitrocellulose, crystalline cellulose Polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylic acid salts, polyalkylene oxide or crosslinked polymer thereof such as polyethylene oxide or polypropylene oxide, carboxyvinyl polymers, such as polyethyleneimine.

(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 type amphoteric surfactant, nonionic surfactant (ether type nonionic) Surfactants, ether ester type nonionic surfactants, ester type nonionic surfactants, block polymer type nonionic surfactants, nitrogen-containing nonionic surfactants), other surfactants (natural surfactants) , Derivatives of protein hydrolysates,
Polymer surfactant, surfactant containing titanium and silicon,
Fluorocarbon surfactants).

(11) Various vitamins Vitamin A group: retinol, retinal (vitamin A ₁ ), dehydroretinal (vitamin A ₂ ), carotene, lycopene (provitamin A), vitamin B group: thiamine hydrochloride, thiamine sulfate (Vitamin B ₁ ), riboflavin (vitamin B ₂ ), pyridoxine (vitamin B ₆ ), cyanocobalamin (vitamin B ₁₂ ), folic acid,
Nicotinic acids, pantothenic acids, biotins, choline,
Inositols, vitamin C group: ascorbic acid and its derivatives, vitamin D group: ergocalciferol (vitamin D ₂ ), cholecalciferol (vitamin D ₃ ),
Dihydrotaxosterol, vitamin E group: tocopherol and its derivatives, ubiquinones, vitamin K group: phytonadione (vitamin K ₁ ), menaquinone (vitamin K ₂ ), menadione (vitamin K ₃ ), menadiol (vitamin K ₄ ), 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, etc. and their sulfates, phosphates, nitrates, citrates, or amino acid derivatives such as pyrrolidone carboxylic acid.

(13) α-Hydroxy acid Glycolic acid, citric acid, malic acid, tartaric acid, lactic acid, etc.

(14) Various additives derived from plant- or animal-based raw materials These are processes (for example, crushing, milling, washing, hydrolysis, etc.) which are conventionally carried out depending on the product type and form to be added. Fermentation, purification, squeezing, extraction, fractionation, filtration, drying, powderization, granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization, etc. are arbitrarily selected and combined, and various materials are selected. You can select and use it. The solvent used for extraction may be selected in consideration of the purpose and type of the product to be provided, the processing to be performed later, and the like. Usually, water or a water-soluble organic solvent (eg ethanol, propylene glycol) is selected. , 1,3-butylene glycol, etc.)
It is desirable to use one or a mixture of two or more selected from the above. However, when the content of the organic solvent is not preferable depending on the use, only water may be used, or ethanol which is easily removed after extraction may be used, and may be used alone or in an arbitrary mixture with water.

Additives derived from plant or animal raw materials are
When applied to systemic or topical external preparations and cosmetics, including protection of skin and hair, moisturizing, improvement of feel and texture,
Gives flexibility, relieves irritation, relieves stress due to aroma, activates cells (prevents cell aging), suppresses inflammation, improves skin and hair quality, prevents and improves rough skin, hair growth, hair growth, hair loss prevention, gloss Application, cleaning effect, alleviation of fatigue, promotion of blood flow,
In addition to cosmetic effects such as a warm bath effect, effects such as flavoring, deodorizing, thickening, preserving, and buffering can be expected. Furthermore, in addition to these, various cosmetic and pharmaceutical effects of each known raw material are expected, and by combining these, the intended effect can be enhanced or multifunctional. It is also possible to make a product that expects an effect.

Specific plants (crude drugs) as raw materials include:
For example, Ai (Aiba), Aokazura (Seifu Fuji), Aotsu-Juraji (Kibo), Acacia, Akasugi fruit, Akagrape, Akamegashiwa (Akabu Kashiwa), Akane (Akane grass root), Akayajiou (Jihuang), Agi (Awei), Akinire (Roasted skin), akebi
(Kidori), Asa (Jin Asako), Asagao (Toshiko), Ashitaba
(Tomorrow's leaf), Adzuki (red azuki bean), Asenyaku (Asenyaku), Acerola, Anise fruit, Abemaki fruit, Avocado, Ama, Amacha (Amacha), Amadokoro (Tamatake), Amigasa lily (Shellfish), Almond, Altea, Arnica , Aloe (log), aloe vera, apricot (almond jelly), ansokkou (benzuka), Igakozolina (biliary head), knotweed (tiger cane root), strawberry, fig (non-flower fruit) or its leaves, strawberry (winter aoiko),
Itohimehagi (Enshi), carob, rice seed or seed coat,
Inondo seeds, nettle, ylang-ylang, ginkgo (gingko leaves, ginkgo), Ibuki-yakosou, fennel (fenka), ukiyagara (sanryou), turmeric fruit, turmeric
(Utsubane), Usbania Oyster, Usbenita Oyster, Usubasaishin (spicy), Utsubogusa (summer hay), Udo or Shishiudo (Qang activity, independence, Tang Dynasty activity), Ume (Umebai) or its pulp, Vladigashi, Uwaurushi, Unshurikan ( Chen), Estragon, Eleuthero (Ezo Goka), Enoki, Ebisugusa (Keiko), Elderberry fruit, Elemi, Enju
(Gossip, Gossip rice), ogre (Astragalus radiata), Ouren (Orchid), Ookarasuri (Karonin), Ootsu-la-Fuji (self-defense), Psyllium (Carmae, Carmaegrass), Toucan (Haruko), Obananaokera ( White ajutsu), fruit beetle fruit, hawthorn
(Yamako), barley (barley), ogurma (turning over), okra fruit, okera (white jujube), panax ginseng (carrot), hypericum (brother's cut grass), odorikosou (intermittent), onamimi (blue ears),
Origurumi, Oninoyagara (Tianma), Oniyuri (Yuri), Oninos, Halibut (Hihayu), Ominaeshi (defeated), Dutch strawberry, Dutch garashi, Dutch parsley, Dutch honeyspot, olive, oregano, orange fruit or peel,
Kaikei (ripe yellow), seaweed [green algae, brown algae, red algae],
Cacao seeds, oysters or their leaves (persimmon), kagi kazura (chou hooks), cassia, casino ki fruit (pepper fruit), gajutsu (shadoju),
Kashiwa (Shaju, Shayo), Cascarilla, Kanixa (Kin Sato),
Valerian (valerian root), squash, capokunoki seed, kahokusansho (pepper), cattail (kamaki), chamomile, kamiyatsude (passing grass), karasuri (flower), oak grass, rasabisaku (midsummer), guarana seeds, karaya, Karin (Gourd Gourd), Kawayanagi, Kawatake Mushroom, Kawamuragi (Inchinko), Kansui (Kansu), Licorice (Licorice), Candelilla, Kanto,
Canna, raspberry, kiwi fruit, kikarasuri (uryu root), kikyo (bellflower, bellflower root), chrysanthemum (chrysanthemum flower), catalpa
(Azumi), Rumex (Yotei root), Kizuta, Kidachi aloe, Kidachi mint, Kinoki, Yellowfin (yellow), Yellowtail
(Astragalus), Gymnema Sylvesta, Kiraja Saponaria, Kiraya, Cabbage, Cabbage Immature Fruit, Cucumber, Kumquat Fruit, Betel, Kinmizuki (Senakurushi), Guayule, Quercus Infectoria (Gallery), Kukuinuts, Kuko (Garium, Gugiko, gugi leaf, ground bone bark), cedar japonicus (tenmon winter), kuzu (kuzukon), camphor tree, gooseberry fruit, gardenia (garden garden), kunugi (bokuso), kumazasa,
Japanese black bean (Coleoptera), Clara (Bittersweet), Cranberry fruit, Chestnut or its astringent skin, Curculigo latifolia fruit, Grapefruit fruit, Buckthorn buckthorn, Black grape mochi (Needs rescue), Kurobana cypress (Enmeisou), Chlorella, Mulberry (Mulberry leaf, Mulberry fruit, mulberry fruit, mussels (thorns, stalks), celosia (cow flower, rooster), keirin saishin (spicy), laurel, gentian, gennoshoko
(Old tomato grass), Cilantro fruit, Koshinbara (Monthly flower), Kosui mint, Kozo fruit, Black tea, Kouhone (Raw bone), Kouhon (Straw and Kara straw), Koulyan, Kokemomo (Koshibachi),
Koganebana (Yellow Gon), Kogomeba Hypericum, Coconut Fruit, Goshuyu (Goshuyu), Goshostrawberry (covered bonko), Pepper (pepper), Copaiba Balsam, Coffee Beans, Kobushi
Burdock, burdock, burdock, sesame
(Sesame seeds), sesame seeds (brown ginseng), wheat (wheat), rice or rice bran (red bran, white bran), cola acuminata seeds, cola vera seeds, fenugreek fruit, colombo, condullango, kelp, comfrey ), Konjac, Sakisima button d'zuru (weird sen), cherry blossoms, leaves, fruits, bark (cherry bark),
Pomegranate, sasa, lily of the valley, lily of the valley, sasanqua, sardines of the sardines (sawashatsu), sweet potato, sugarcane, sugar beet,
Jujube jujube (acid jujube), saffron (ban safflower, western safflower),
Pomelo fruit, Soapwort, Salmonberry fruit, Sarashina-sho (Masahima), Salvia, Sawagikyo (Yamakona),
Sawagurumi leaves, Sankirai (Yamakoi), Hawthorn (Yamako), Sanshin ginseng (Sanjin ginseng), Sanshuyu (sanshuyu), Sansho (sansho), Sandscon (Yamazone), Cyanoki fruit, Shiitake mushroom, Jio (Jiro), Shion (Shi-en), Digitalis, Shikunshi (Kimiko), Shishiudo (Independent, Tang-do),
Perilla, Aojiso, Chirimenzo, Catamendiso (Shiyo leaf, Shiso), Weeping birch (white birch bark), Rosewood, Linden tree, Chinese beetle (Forestry), Shimakaniku (Chrysanthemum flower), Shimotsukesou, Potato, Peony (Shakuyaku), Shajin
(Sasan), Scotch beetle (Wheat gate winter), Shirakashi seed, Shirogoshi butterfly seed, Shirobanairisu, Shirobanatsuta flower, Shirominanten (South Tenmi), Juzudama, Palm fruit, Ginger (Ginger), Shoubu (Iris, Iris root) , Shozuku fruit, Birch, Cinconas sacyl bra, Cinnamon, Watermelon
(Watermelon), honeysuckle (gold and silver flowers, shintofu), sorrel (acidic pattern), swimberry fruit, strawberry fruit, horsetail (infestation), stevia, plum fruit, pine cone, pine larch, euphorbia edulis, edible walnut, Pear fruit, snowy pear, oilseed meadow, oilseed americanum, oilseed walnut, oilseed smelt, mint, euphoria melanogaster, euphoria dolphini, edible mackerel, euphorbia, saccharomyces, sacrum Kawakyu), Senna fruit or leaves, Senninsou (large tate), Japanese cabbage (medicine), Soka (grass), buckwheat seeds, Somei potato, Daio (Ohio), Radish, soybean, Daidai (orange peel, Kikomi), Thyme , Takatodai (Daigei), Takawarabi (Inu), Dark Sweet Ferry fruit, Thymus vulgaris (HyakuRika), Tachibana (Tachibanakawa), Tachiyanagi, tamarind seeds, onions, Magnolia salicifolia (fist), Aralia elata or the root bark, Danshen (Dan Shen), dammar, cherry fruit,
Chigaya or its roots (Chiyone), chicory, cloves (cloves, cloves), daffodil (gomiko), daffodil
(Ohta), Korean ginseng (Wuyi), Korean ginseng
(Ginseng), Artemisia (Aiba), Choreimaitake
(Irei), Tsukimiso, Camellia, Camellia, Tsumekusa (lacquer lacustrine), Tsurukusa (duckling grass), Tsuruazuki (red azuki bean), Tsurudukudami (Hanshukara), Tsuruna (Kankyo), Tsurujinjin (Four leaf ginseng), Tsuwabuki, Deiko , Teuchigurumi, Duberry fruit, Tengusa, Tendaiyaku (crow medicine), Touga (Winter melon), Pepper (Pan pepper), Touki (Toki), Toukinsenka, Maize or Maize hair (Nanban hair), Tosumi Mochi (Female Sadako) , Tourindo (dragon gall), dokudami (jujutsu), radish (tomato), tochiban ginseng (bamboo ginseng), eucommia (tochu, tochuha), tomato, tragacanth, triacanthos seed, tormentilla, dronoki, troloi, nigeriaberry fruit , Potatoes (herbal medicine), nagi-kida, naginatakoju, nazuna, jujube, jujube (daijutsu),
Naniwaibara (Kanekurako), Narco Lily (Yoshisei), Peanut (Peanut), Nanten (Namitenmi), Nigaki (Makiki), Nigayomogi (Gakui), Nikuzuku, Nikkei (Kisushi), Leek (Nirako),
Elderberry (bone grafted), carrot, garlic (garlic), nurde
(Five-fold child), leek, thistle (daiji), noibara (fruit), yarrow, nodake (maehu), nobara, peach, palm,
Hibiscus (Bussouge, Furin-Bussouge, Roselle), Pineapple fruit, Hakata lily (Yuri), Hakaumauraboshi (Bone crushing supplement), Hakusen (White moss bark), Huckleberry fruit, Hakobe (Resurrection), Hazelnut (Haruko), Hashidokoro (Roth root) , Basil, lotus (lotus meat, lotus root), parsley, batata, wasp (bamboo-boiled), patchouli, mint (light load, light load leaf), barley (yokuinin), hanasuge (chimomo), banana, hanahakka, vanilla bins, papaya, Stilt
(Mouse malt grass), hub grass, paprika, hamago (vine thorns), hamasuge (kosuke), hamabishi (situriko), hamanas (my rose flower), hamabafu (beach storm), hamamelis, rose (rose), parietalia , Harunile (Yu, YuYi, Yuba),
Breadfruit, Chinese cedar (irrigation), medusa carrots (participants), pecan nuts, hemp trees (stone garlic, lily flower),
Hikiokoshi (prolonged life grass), Hishi (Hishimi), pistachio, beet, Hitotsuba (stone reed), Hinata Kozuchi (cow knee), Hiba,
Castor, Sunflower, Bell Pepper, Himegama (Incense Bulb), Himematsutake, Pimenta Fruit, Hiyu Fruit, Below Oyster, Hiroha Kinagusa (Hakuto Okina), Hiroha Senega (Senega), Loquat
(Loquat, loquat leaf), betel nut (large belly skin, betel roe), sprouts (southern wisteria), butterbur (winter winter flowers), and coltsfoot (winter winter flowers,
Subsidiary winter leaves), Fujibakamama (orchid), Fuji beans (bean beans), butcher bloom, grape peel or fruit, beech, Fuyumushinatsukutake mushroom (Cordyceps sinensis), Brazilian liquorice, black currant fruit, blackberry fruit, plum fruit, furcellaria, blueberry Fruit, prune, blond psyllium, bundou (mung bean), loofah, safflower (safflower), belladonna, berry fruit, boysenberry fruit, boufu
(Windbreak), spinach, physalis (Torone), honoki
(Thick, Japanese Thick), Bokeh (Gourd), Hosobaokera (Sojutsu), Hosobabarengiku, Bodaiju, Button (peony bark), Hop, Jojoba, Whiteberry Berry Fruit, Honganzu (Apricot Jin), Hongshimeji, Meisultennanshaw ( Tiannan star),
Ephedra (maoh), macadamia nuts, macri (sea grass), maguwa (mulberry leaves, mulberry bark), madatake (bamboo boiled), matabi (mokuten tate), matsukasa, matsuhodo (bukuryo), marigold, malvanozadine (apricot) ), Mulberry fruit, quince, horse chestnut, mango, mangosteen, mansugurumi,
Mandarin fruit, mannentake (reishi), mannenrow,
Citrus fruit (Colourful), Mishima Psycho (Saiko), Mizokakushi (Harenbei lotus), Misohagi (Sengansai), Mitsugashiwa, Mitsuba, Mitsubahamago (vine vine), Midorihakka, Mimosa,
Ginger, miracle fruit fruit, myrrh, myrobaran, mugwort (Moon Geese), mukunoki, mukuroji, murasaki (purple root), murasaki maize, mehajiki (benefit mother grass), mebuki, melaleuca, melissa, melilot, melon fruit, mokoyomikoku, mokurenposhi ), Mokko (Kinko), Maple Butterfly, Peach Fruit, Seed (Peach) or Leaf (Peach), Sprouts, Morero Cherry Fruit, Moroheiya, Yakawamurasakiimo, Yakuchi (Masuchi), Cornflower, Cornflower, Cornflower Mint, yashabushi (arrow wheel), yachiyanagi, yatsude (octagonal gold plate), mistletoe (parasitic willow), willow leaf, yabugarashi, yabukouji (purple gold beef), pokeweed (land), yamanoimo (yakuyaku), yamahanoki (yamaharu) ), Bayberry (Yumebai skin), Eucalyptus, Yucca Brevifolia, Yukinoshita (Tiger ear grass), Yuzu Real, lily,
Artemisia (Aiba), yogurusa, lime fruit, peanut, lakanka fruit, raspberry fruit, lavender, longan
(Dragon meat), green tea, apple fruit, Rubus suabicimus
(Sweet), lettuce, red currant fruit, lemon fruit,
There are lemongrass, forsythia (forsythia), forsythia, wax palm, loganberry fruit, rosehip, rosemary, Roman chamomile, wakame, wasabi, waremoko (earthworm).

Materials derived from animal-derived raw materials include chicken cob extract, cow / human placenta extract, pig / cow stomach, duodenum or intestinal extract or its decomposition product, pig / cow spleen extract. Or its decomposition products, extracts of brain tissue of pigs and cows,
Water-soluble collagen, collagen derivative such as acylated collagen, collagen hydrolyzate, elastin, elastin hydrolyzate, water-soluble elastin derivative, keratin and its degradation product or their derivatives, silk protein and its degradation product or their derivatives, Pig / Bovine blood cell proteolysis product (globin peptide), Pig / cow hemoglobin degradation product (hemin, hematin, heme, protoheme, heme iron, etc.), milk,
Casein and its degradation products or their derivatives, skim milk powder and its degradation products or their derivatives, lactoferrin or its degradation products, chicken egg components, fish meat degradation products, etc.

(15) Microbial Culture Metabolites Yeast metabolites, yeast extract, rice fermentation extract, rice bran fermentation extract, Euglena extract, lactic acid fermented skim milk powder, etc.

(16) 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, red iron oxide, black iron oxide, gunjou, chromium oxide,
Chromium hydroxide, carbon black, calamine, etc.

(17) UV absorber p-aminobenzoic acid derivative, salicylic acid derivative, anthranilic acid derivative, coumarin derivative, amino acid compound,
Benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives, camphor derivatives, furan derivatives, pyrone derivatives,
Nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives,
Vitamin B ₆ derivatives, oxybenzone, benzophenone, guaiazulene, shikonin, baicalin, baicalein, berberine and the like.

(18) Astringent succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc p-phenolsulfonate, potassium aluminum sulfate, resorcinol, ferric chloride, tannic acid (including catechin compounds) Such.

(19) Antioxidants ascorbic acid and its salts, stearic acid esters, tocopherol and its ester derivatives, nordihydroguaseletenic acid, butylhydroxytoluene (BHT),
Butylhydroxyanisole (BHA), hydroxytyrosol, parahydroxyanisole, propyl gallate, sesamol, sesamolin, gossypol and the like.

(20) Anti-inflammatory agent Ictamole, indomethacin, kaolin, salicylic acid, sodium salicylate, methyl salicylate, acetylsalicylic acid, diphenhydramine hydrochloride, d or dl-
Camphor, hydrocortisone, guaiazulene, camazulene, chlorpheniramine maleate, glycyrrhizic acid and its salts, glycyrrhetinic acid and its salts and the like.

(21) Disinfectant / Disinfectant Acrinol, sulfur, benzalkonium chloride, benzethonium chloride, methylrosaniline chloride, cresol, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin or a hydrolyzate thereof.

(22) Fragrances Natural animal fragrances such as musk, civet, catrium, ambergris, anise essential oil, angelica essential oil, ylang-ylang essential oil, iris essential oil, fennel essential oil, orange essential oil, cananga essential oil, karaway essential oil, cardamom essential oil, Guayakwood essential oil, cumin essential oil, black character 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 Mint essential oil, large scented essential oil, tuberose essential oil, Choji essential oil, orange flower essential oil, winter green essential oil, true balsam essential oil, butchery essential oil, rose essential oil, palmarosa essential oil, cypress essential oil, hiba essential oil,
Sandalwood essential oil, Petitgren essential oil, Bay essential oil, Vetiva essential oil, Bergamot essential oil, Peruvian balsam essential oil, Boad rose essential oil, Camphor essential oil, Mandarin essential oil, Eucalyptus essential oil, Lime essential oil, Lavender essential oil, Linaloe essential oil, Lemongrass essential oil, Lemon essential oil, Rosemary Vegetable flavors such as essential oils and Japanese peppermint essential oils, and other synthetic flavors.

(23) Dyes / Colorants Red cabbage dye, red rice dye, madder dye, anato dye, squid dye, turmeric dye, endu dye, krill dye, persimmon dye, caramel, gold, silver, gardenia dye, corn dye , Onion pigment, tamarind pigment, spirulina pigment, whole buckwheat pigment, cherry pigment, laver pigment, hibiscus pigment, grape juice pigment, marigold pigment, purple potato pigment, purple yam pigment, lac pigment, rutin, etc.

(24) Other moisturizers, hormones, sequestering agents, pH adjusters,
Chelating agents, antiseptic / antifungal agents, cooling agents, stabilizers, emulsifiers, animal / vegetable protein and its degradation products, animal / vegetable polysaccharides and its degradation products, animal / vegetable glycoprotein and its degradation products, Blood flow promoters, anti-inflammatory agents / anti-allergic agents, cell activating agents, keratolytic agents, wound healing agents, foaming agents, thickening agents, oral agents, deodorizing / deodorizing agents, enzymes, etc. When used in combination, additive and synergistic effects can be expected.

[0045]

EXAMPLES Preparation of Various Formulations N-acetyltyrosine derivatives according to the present invention were used to prepare some topical formulations. The formulation examples are shown below, but the use of the melanin production inhibitor according to the present invention is not limited to these.

1) Production Example of Lotion A lotion was produced according to the following formulation. % By weight Sorbit 2 2.1,3-butylene glycol 2 3. Polyethylene glycol 1000 1 4. Polyoxyethylene oleyl ether (25E.O.) 25 Ethanol 10 6. N-acetyltyrosine 1 7. Sodium lactate 0.2 8. pH adjuster qs 9. Preservative appropriate amount 10. Purified water 100 residue

2) Production Example of Emulsion An emulsion was produced according to the following formulation. % By weight Squalane 3 2. Vaseline 1 3. Stearyl alcohol 0.3 4. Sorbitan monostearate 1.55. Polyoxyethylene (20) sorbitan monooleate 3 6.1,3-butylene glycol 5 7. N-acetyl tyrosine ethyl ester 0.5 8. Glycolic acid 0.19. Preservative appropriate amount 10. Purified water 100 residue

3) Cream Production Example A cream was produced according to the following formulation. % By weight Squalane 20 2. Beeswax 5 3. Refined jojoba oil 5 4. Glycerin monostearate 2 5. Sorbitan monostearate 2 6 Polyoxyethylene (20) sorbitan monostearate 2 7. Glycerin 5 8. N-acetyl tyrosine sodium 1 9. Sodium citrate 0.2 10. Preservative appropriate amount 11. Purified water 100 residue

4) Shampoo Production Example A shampoo was produced according to the following formulation. % By weight Triethanolamine lauryl sulfate 5 2. Polyoxyethylene lauryl ether sulfate Na 12 3.1,3-butylene glycol 4 4. Lauric acid diethanolamide 2 5. Disodium edetate 0.1 6. N-acetyl tyrosine potassium 27. Sodium tartrate 0.2 8. Preservative appropriate amount 9. Purified water 100 residue

5) Production Example of Body Soap A body soap was produced according to the following formulation. % By weight Potassium laurate 15 2. Potassium myristate 5 3. Propylene glycol 5 4. N-acetyl tyrosine 25. Sodium citrate 0.1 6. Sodium lactate 0.1 7. pH adjuster Appropriate amount 8. Preservative appropriate amount 9. Purified water 100 residue

6) Production Example of Bath Agent (A Type) A bath agent was produced according to the following formulation. % By weight Sodium hydrogen carbonate 50 2. Anhydrous sodium sulfate 25 3. Borax 2 4. N-acetyl tyrosine potassium 10 5. N-acetyl tyrosine ethyl ester 10 6. Sodium lactate 2 7. Sodium glycolate 1

7) Production Example of Bath Agent (Type B) A bath agent was produced according to the following formulation. % By weight Refined jojoba oil 5 2. 2. Polyoxyethylene sorbitan monolaurate 20 Glycerin monostearate 5 4. Liquid paraffin 2 5. Lauric acid diethanolamide 3 6. N-acetyl tyrosine 20 7. Sodium lactate 1 8 Purified water 100 residue

[0053]

[Example] Use test of various external preparations Male and female panelists (15 persons each) were allowed to freely use the lotion and the bath preparation manufactured in the example for one month, and a questionnaire survey on feeling of use was requested. The results are shown in Table 3.
It is as follows.

[Table 3]

[0054]

The melanin production inhibitor according to the present invention is excellent in its effect and highly safe. For example, by blending it with various skin external preparations that are routinely used, and by repeatedly using them, spots, freckles, dullness,
It reduces or prevents blackening of the skin, adjusts the texture of the skin (improves the skin quality itself), and provides excellent skin-beautifying effects such as moisturizing. The cosmetic effect and the application method based on the cosmetic effect according to the present invention contribute to the beauty and health of a person by a very ordinary method.

Continuation of front page (51) Int.Cl. ⁶ Identification number Office reference number FI Technical display location A61K 31/215 ADA A61K 31/215 ADA // C07C 233/47 9547-4H C07C 233/47

Claims (2)

[Claims] 1. N-acetyl tyrosine, N-acetyl tyrosine sodium, N-acetyl tyrosine potassium, N
1 selected from acetyl tyrosine ethyl ester
A melanin production inhibitor containing one or more N-acetyltyrosine derivatives as an active ingredient. 2. A skin external preparation or bath preparation containing the melanin production inhibitor according to claim 1, which contains an N-acetyltyrosine derivative as an active ingredient.