JP4377263B2 - Cosmetics and external preparation for skin - Google Patents

Description

  Amino acid zinc salts and zinc complexes crystallize over time in the formulation without the use of solubilizers. Since zinc salts and zinc complexes of crystallized amino acids are not absorbed by the skin, there are problems such as the whitening effect and anti-aging effect that are the original functions of the zinc salts and zinc complexes of amino acids are not effectively exhibited. . The present invention relates to stably blending an amino acid zinc salt and / or zinc complex into a skin external preparation without losing its effect.

  It is well understood that active oxygen is produced by the irradiation of the skin with solar ultraviolet (UV) radiation. Active oxygen causes various damages such as DNA damage to the skin, and ultimately enhances photoaging of the skin. Therefore, a method for reducing stimulation by active oxygen and preventing photoaging is desired. In general, the use of radical scavengers (administration from outside the cell) seems to be effective in preventing the progression of photoaging due to active oxygen, but since many radical scavengers are unstable, a large amount of substance is administered continuously. It is difficult to obtain effective effects.

  On the other hand, metallothionein, whose production is known to be induced by multiple heavy metals, is generally considered to be mainly responsible for the detoxification of heavy metals, but it has become clear that it has further antioxidant activity and inflammation. It has been reported to act as a scavenger for free radicals that occur occasionally. (See Non-Patent Document 1)

  In this regard, it has been demonstrated in cultured cell systems that cell damage due to active oxygen is reduced by externally adding a substance that induces metallothionein production in skin cells.

  As metallothionein production inducers, metals such as zinc, cadmium, copper, mercury, gold, silver, and bismuth are known. Among them, zinc is particularly preferable in terms of safety. However, in general, in the state of a free metal ion, due to its charge, the permeability to the skin and the efficiency of cellular uptake are low, and induction of metallothionein in the subepidermal region by external application cannot be expected. In view of this, there is a method of improving the permeability to the skin and the efficiency of uptake into cells by using salts or complexes with various amino acids. However, zinc salts and zinc complexes of amino acids are poorly soluble in water and components generally used in external preparations for skin, and have the drawback of crystallizing with time in the preparation. Since zinc salts and zinc complexes of crystallized amino acids are not absorbed by the skin, there are problems such as the whitening effect and anti-aging effect that are the original functions of the zinc salts and zinc complexes of amino acids are not effectively exhibited. .

As an example of blending an amino acid zinc salt or zinc complex into a skin external preparation, there are three reports in the patent literature, but there is a problem of crystallization with any of the skin external preparation base materials, permeability to the skin and into the cell. However, the effect of inducing metallothionein production by skin cells is insufficient. (See Patent Documents 1 to 3)
(Hanada K. et al., Dermatologica, vol. 179 (suppl. 1), p. 143, 1989) Japanese Patent Application No. 5-513101 Japanese Translation of National Publication No. 06-504719 JP-T-2001-503044

  When an amino acid zinc salt or zinc complex is contained alone in a topical skin preparation, crystallization occurs over time, and the whitening effect and anti-aging effect that are inherent functions of the amino acid zinc salt or zinc complex are effective. It is not demonstrated. Therefore, zinc salts and / or zinc complexes of amino acids that do not crystallize even in the skin external preparation base material, have high permeability to the skin and uptake into cells, and have sufficient effects of inducing metallothionein production of skin cells. It was an object of the present invention to provide a formulated skin external preparation.

  Water soluble as a solubilizer to enhance the solubility of amino acid zinc salts and / or zinc complexes in topical skin preparations containing amino acid zinc salts and / or zinc complexes and prevent crystallization over time A skin external preparation having a high skin permeation and cellular uptake efficiency and sufficient whitening effect and anti-aging effect by adding an organic acid and / or salt thereof, amino acid and / or salt thereof. It can be provided.

  INDUSTRIAL APPLICATION This invention can mix | blend the zinc salt and / or zinc complex of amino acids stably with a skin external preparation, and can exhibit the whitening effect and the anti-aging effect effectively. Further, it was found that a skin external preparation containing a zinc salt of amino acids and / or a zinc complex can be provided as a skin external preparation having no problem in temperature stability over a long period of time.

The zinc salt of amino acids used in the present invention is a salt of amino acids and zinc, and the zinc complex of amino acids is a zinc complex of amino acids in which the amino acids are bonded to zinc via a coordination bond. Zinc salts and zinc complexes of amino acids can be prepared from known amino acids and zinc salts. For example, it can be prepared by the method disclosed in JP-T-2001-503044. In the present invention, zinc salts of amino acids and zinc complexes of amino acids can be used alone or in combination.
Examples of the zinc salt include zinc chloride and zinc oxide.

  The amino acids may be neutral amino acids, basic amino acids, or acidic amino acids as long as they can form a salt or complex with zinc. For example, glycine, cysteine, alanine, serine, genolic acid, γ --Aminobutyric acid, threonine, valine, methionine, leucine, isoleucine, phenylalanine, tyrosine, thyroxine, proline, hydroxyproline, tryptophan, taurine, glutamic acid, aspartic acid, arginine, DL-pyrrolidone carboxylic acid, lysine, ornithine, histidine, taurine, N-methyl taurine etc. are mentioned, These may be any of D-form, L-form, and DL-form.

  Specific examples of the zinc salts of amino acids in the present invention include glycine zinc complexes and cysteine zinc complexes. One or more zinc salts of amino acids are used.

  Specific examples of the zinc complex of amino acids in the present invention include glycine zinc salt, cysteine zinc salt and the like, and one or more zinc complexes of amino acids are used.

  The peptide may be a natural or synthetic peptide. Synthetic peptides include, for example, oligopeptides having 2 to 10 amino acids such as dipeptides, tripeptides, tetrapeptides, pentapeptides, hexapeptides, heptapeptides, octapeptides, nonapeptides, decapeptides, etc., in which the same or different amino acids are combined. Can be mentioned. The amino acids constituting these peptides may be a single amino acid or a combination of two or more different amino acids.

  Examples of natural peptides include linear peptides such as glutathione and carnosine, cyclic peptides such as gramicidin, hormones such as oxytocin, vasopressin, and insulin, hydrolyzed elastin, water-soluble elastin, hydrolyzed collagen, water-soluble collagen, casein, Cosmetic base materials such as glutathione, wheat peptide, soybean peptide and the like can be mentioned.

  Examples of the water-soluble organic acid used in the present invention include alkanoic acid, saturated dibasic acid, oxycarboxylic acid and the like. For example, alkanoic acid includes methanoic acid, ethanoic acid, propanoic acid, butanoic acid, pentanoic acid, hexanoic acid, heptanoic acid, and the like, and saturated dibasic acid includes oxalic acid, malonic acid, succinic acid, glutaric acid Examples of the oxycarboxylic acid include citric acid, glycolic acid, tartaric acid, and lactic acid. Other examples include vitamins such as ascorbic acid. In the present invention, oxycarboxylic acid is particularly suitable. Examples of the water-soluble organic acid salt include alkali metal salts of the organic acids, such as trisodium citrate and sodium lactate. Of these, citric acid and trisodium citrate are particularly preferably used. In the present invention, one or more of these organic acids and salts thereof can be arbitrarily selected and used.

  The amino acid used in the present invention and / or the amino acid constituting the salt thereof may be any of neutral amino acids, basic amino acids, and acidic amino acids, such as glycine, alanine, valine, leucine, isoleucine, serine, threonine, phenylalanine, Tyrosine, tryptophan, cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid, asparagine, glutamic acid, glutamine, arginine, histidine, lysine, γ-aminobutyric acid, DL-pyrrolidone carboxylic acid, ε-aminocaproic acid, etc. These may be any of D-form, L-form, and DL-form. Among these amino acids, particularly preferred amino acids are proline, hydroxyproline, lysine hydrochloride, DL-serine, threonine, alanine, and L-arginine. Examples of amino acid salts include alkali metal salts and hydrochlorides of amino acids. In the present invention, one or more of these amino acids and salts thereof can be arbitrarily selected and used.

  The blending amount of amino acid zinc salt and / or zinc complex in the external preparation for skin of the present invention is preferably 0.01 to 10% by weight in the total amount of external preparation for skin. Particularly preferred is 0.05 to 5% by weight.

Furthermore, when the amino acid zinc salt and / or zinc complex is (A), the water-soluble organic acid and / or salt thereof is (B), and the amino acid and / or salt thereof is (C), the present invention About the compounding quantity and composition ratio (weight ratio) of (A)-(C) component in the skin external preparation total amount of, the following range is preferable.
(A) + (B) + (C) = 0.1-30 wt%
(A) / (B) or (A) / (C) = 0.001 to 99
(A) / (B) + (C) = 0.001 to 99
Preferably,
(A) + (B) + (C) = 0.2-15% by weight
(A) / (B) or (A) / (C) = 0.02-9
(A) / (B) + (C) = 0.02-9

  In the external preparation for skin according to the present invention, a water-soluble polymer can be further blended, the stability is improved by the thickening action and emulsification assisting action of the water-soluble polymer, further improvement of dispersibility, and imparting a moisturizing feeling. The effect of zinc salts of amino acids and / or zinc complexes can be enhanced by improving the feeling of use and forming a film. Examples of water-soluble polymers include acrylic acid ester / methacrylic acid ester copolymers (Availure AC and Carbopol Aqua SF-1: Noveon, plus size: manufactured by Kyoyo Chemical Co., Ltd.), vinyl acetate / crotonic acid copolymer (resin 28 -1310: manufactured by NSC), vinyl acetate / crotonic acid / vinyl neodecanate copolymer (28-2930: manufactured by NSC), methyl vinyl ether maleic acid half ester (Gantrez ES: manufactured by ISP), t-butyl acrylate / Ethyl acrylate / methacrylic acid copolymer (Rubimer: manufactured by BASF), vinylpyrrolidone / vinyl acetate / vinyl propionate copolymer (rubiscol VAP: manufactured by BASF), vinyl acetate / crotonic acid copolymer ( Ruby Set CA: BASF , Vinyl acetate / crotonic acid / vinyl pyrrolidone copolymer (ruby set CAP: manufactured by BASF), vinyl pyrrolidone / acrylate copolymer (ruby flex: manufactured by BASF), acrylate / acrylamide copolymer (ultra hold: manufactured by BASF) ), Vinyl acetate / butyl maleate / isobornyl acrylate copolymer (Advantage: manufactured by ISP), carboxyvinyl polymer (Carbopol: manufactured by Noveon), acrylic acid / alkyl methacrylate copolymer (Pemulen: Noveon) Anionic polymer compounds such as dialkylaminoethyl methacrylate polymer (Yukaformer: manufactured by Mitsubishi Chemical Corporation), octyl acrylamide / hydroxypropyl acrylate / meta Amphoteric polymer compounds such as butylaminoethyl acrylate copolymer (AMPHOMER: manufactured by NSC), quaternized vinylpyrrolidone / dimethylaminoethyl methacrylate (GAFQUAT: manufactured by ISP), methylvinylimidazolium chloride / vinylpyrrolidone Cationic polymer compounds such as polymers (ruby coat: manufactured by BASF), polyvinylpyrrolidone (rubiscol K: manufactured by BASF), vinylpyrrolidone / vinyl acetate copolymer (rubiscol VA: manufactured by BASF), vinylpyrrolidone / Nonionic polymer compounds such as dimethylaminoethyl methacrylate copolymer (copolymer 937: manufactured by ISP), vinylcaprolactam / vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer VC713: manufactured by ISP), etc. The Cellulose or derivatives thereof, keratin and collagen or derivatives thereof, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharide, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabino Contains naturally occurring polymer compounds such as galactan, karaya gum, gum tragacanth, alginic acid, albumin, casein, curdlan, gellan gum, dextran, gluco-oligosaccharide (Bioecolia: Soravia), fucose-containing polysaccharide (Fucogel 1000PP: Soravia), rhamnose Polysaccharides (Rhamnosoft: Solavia) can also be suitably blended. Among these, nonionic polymer compounds and naturally derived polymer compounds are preferable in terms of salt resistance. In particular, cellulose or a derivative thereof, xanthan gum, and guar gum are preferable. The blending amount of the water-soluble polymer is prepared based on thickening action, emulsification assisting action, improvement in feeling of use, improvement in dispersibility, etc., but 0.001 to 5% by weight in the total amount of the external preparation for skin of the present invention. Is preferred. Most preferably, it is 0.01 to 2 weight%.

  In addition to the above components, the external preparation for skin of the present invention is a component used in cosmetics, external preparations for skin, etc. within the range not impairing the effects of the present invention, such as oil, higher alcohol, fatty acid, ultraviolet absorber, powder , Pigments, surfactants, polyhydric alcohols / sugars, polymers, physiologically active ingredients, solvents, antioxidants, perfumes, preservatives, and the like.

Examples are listed below, but the present invention is not limited to these examples.
(1) Example of oil

Ester-based oil phase components: glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, butyl stearate, Butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, diisopropyl adipate, isoaralkyl neopentanoate , Tri (capryl / capric acid) glyceryl, tri-2-ethylhexanoic acid trimethylolpropane, triisostearic acid trimethylolpro Tetraethyl 2-ethylhexanoate pentaerythritol, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isolaurate Stearyl, isotridecyl myristate, isocetyl myristate, isostearyl myristate, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl linoleate, octyldodecyl isoleate, isopropyl isostearate Cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate Cole, ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di (capryl / capric acid), propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, triisopalmitine Glyceryl acid, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyl decyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleic acid Ester, polyglycerol isostearate, dipropyl carbonate, Dialkyl carbonate (C12-18), triisocetyl citrate, triisoaralkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyl decyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate , Trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, Cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, 12-stearoyl hydride Kishisutearin isocetyl, 12-stearoyl-hydroxystearic acid stearyl 12-stearoyl-hydroxystearic acid isostearate, and the like.
Hydrocarbon oil phase components: squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum and the like.
Animal and vegetable oils and their hydrogenated oils, and naturally occurring waxes: beef tallow, hydrogenated beef tallow, lard, hydrogenated tallow, horse oil, hydrogenated horse oil, mink oil, orange luffy oil, fish oil, hydrogenated fish oil, egg yolk oil and other animal oils and Its hardened oil, avocado oil, almond oil, olive oil, cacao butter, apricot kernel oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil, camellia oil Corn oil, rapeseed oil, hardened rapeseed oil, palm kernel oil, hardened palm kernel oil, palm oil, hardened palm oil, peanut oil, hardened peanut oil, castor oil, hardened castor oil, sunflower oil, grape seed oil, jojoba oil , Hardened jojoba oil, macadamia nut oil, medhome oil, cottonseed oil, hardened cottonseed oil, coconut oil, hardened coconut oil and other vegetable oils and their hardened oils, beeswax, high acid value beeswax, la Phosphorus, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax and montan wax.
Silicone oil phase components: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethyl Siloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic Examples include silicone, trimethylsiloxysilicic acid, and silicone RTV rubber.
Fluorine oil phase components: perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl / polyoxyalkylene co-modified organopolysiloxane, and the like.
(2) Examples of higher alcohols

Examples include lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, octyldodecanol and the like.
(3) Examples of fatty acids

Caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid, erucic acid, 2- Examples include ethylhexanoic acid.
(4) Examples of UV absorbers

Paraaminobenzoic acid, amyl paraaminobenzoate, ethyl dihydroxypropyl paraaminobenzoate, glyceryl paraaminobenzoate, ethyl paraaminobenzoate, octyl paraaminobenzoate, octyldimethyl paraaminobenzoate, ethylene glycol salicylate, octyl salicylate, triethanolamine salicylate, salicylic acid Phenyl, butyl phenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl paramethoxycinnamate, 2-ethylhexyl paramethoxycinnamate, mono-2-ethylhexanoic acid glyceryl diparamethoxycinnamate, paramethoxysilicate Isopropyl cinnamate, paramethoxyhydrocinnamic acid diethanolamine salt, diisopropyl diisopropyl cinnamate ester mixture, Locanoic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenonesulfonic acid and its salt, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, butylmethoxydi Benzoylmethane, 2,4,6-trianilino-p- (carbo-2-ethylhexyl-1-oxy) -1,3,5-triazine, 2- (2-hydroxy-5-methylphenyl) benzotriazole, methyl- O-aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate, phenylbenzimidazole Acid, 3- (4-methylbenzylidene) camphor, isopropyldibenzoylmethane, 4- (3,4-dimethoxyphenylmethylene) -2,5-dioxo-1-imidazolidinepropionate 2-ethylhexyl, and the like Examples thereof include molecular derivatives and silane derivatives.
(5) Examples of powders and pigments

Red No. 104, Red No. 201, Yellow No. 4, Blue No. 1, Black No. 401, Basic dyes, HC colors, disperse dyes, pigments such as direct dyes, yellow No. 4 AL lake, yellow No. 203 BA lake etc. Pigment, nylon powder, silk powder, urethane powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polymers such as polyethylene powder, yellow iron oxide, red iron oxide, black iron oxide, Colored pigments such as chromium oxide, carbon black, ultramarine and bitumen, white pigments such as zinc oxide, titanium oxide, and cerium oxide, extender pigments such as talc, mica, sericite, kaolin, and plate-like barium sulfate, and pearls such as titanium mica Pigment, barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, silicate mug Metal salts such as calcium, inorganic powders such as silica and alumina, metal soap such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, zinc undecylenate, bentonite, smectite And boron nitride. There are no particular restrictions on the shape of these powders (spherical, rod-like, needle-like, plate-like, irregular shape, flake-like, spindle-like, etc.) and particle diameter. These powders are conventionally known surface treatments such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil agent treatment, N-acylated lysine treatment, The surface treatment may or may not be performed in advance by polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment or the like.
(6) Examples of surfactants

Anionic surfactant: fatty acid soap, α-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate, alkyl amide sulfate, alkyl phosphorus Acid salt, POE alkyl phosphate, alkylamide phosphate, alkyloyl alkyl taurate, N-acyl amino acid salt, POE alkyl ether carboxylate, alkyl sulfosuccinate, sodium alkyl sulfoacetate, acyl isethionate, acylation Examples include hydrolyzed collagen peptide salts and perfluoroalkyl phosphate esters.
Cationic surfactant: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride , Behenic acid amidopropyldimethylhydroxypropylammonium chloride, stearic acid diethylaminoethylamide, stearic acid dimethylaminopropylamide, lanolin derivative quaternary ammonium salts, and the like. Moreover, tertiary amines, such as fatty acid amide dialkylamine, and its salt are also mentioned.
Amphoteric surfactants: carboxybetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type, amide sulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amidoamine type and the like.
Nonionic surfactant: propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE sorbit fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE cured castor Oil, POE castor oil, POE / POP copolymer, POE / POP alkyl ether, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid and the like.
Natural surfactant: lecithin, saponin, sugar surfactant and the like.
(7) Examples of polyhydric alcohols and sugars

Ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerol, diglycerol, polyglycerol, 3-methyl-1,3-butanediol, 1,3-butylene glycol, sorbitol, mannitol, raffinose, Examples include erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, and pullulan. These chemically modified compounds can also be used.
(8) Examples of bioactive ingredients

  Examples of the physiologically active ingredient include substances that impart some physiological activity to the skin when applied to the skin. For example, whitening, anti-inflammatory, anti-aging, UV protection, slimming, squeezing, anti-oxidation, hair growth / hair growth, moisturizing, blood circulation promotion, antibacterial / sterilization, cold / warm feeling, wound healing promotion, stimulation relaxation, analgesia, cells It is a component having effects such as activation, and examples thereof include plant extracts, seaweed extracts, vitamins and derivatives thereof, biopolymers such as amino acids, peptides, mucopolysaccharides, enzyme components, and the like. Examples of these suitable ingredients include, for example, ashitaba extract, avocado extract, amacha extract, altea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, isoflavone, ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract , Ages extract, Echinacea leaf extract, Ogon extract, Oat extract, Auren extract, Barley extract, Hypericum extract, Oyster extract, Dutch mustard extract, Orange extract, Cacao extract, Seawater dried product, Seaweed extract, Hydrolyzed elastin, Hydrolyzed wheat Powder, hydrolyzed silk, pumpkin seed extract, chamomile extract, carrot extract, cormorant extract, licorice extract, calcade extract, oyster extract, kiwi extract, kina extract, cuecan -Extract, Guanosine, Gardenia extract, Kumazasa extract, Clara extract, Cranberry extract, Walnut extract, Grapefruit extract, Clematis extract, Chlorella extract, Mulberry extract, Gentian extract, Black tea extract, Yeast extract, Burdock extract, Rice bran extract, Rice germ oil, Comfrey extract, Collagen, Cowberry extract, Saishin extract, Psycho extract, Saitai extract, Salvia extract, Soap extract, Sasa extract, Hawthorn extract, Salamander extract, Shiitake extract, Giant extract, Shikon extract, Perilla extract, Linden extract, Shimotake extract Peonies extract, ginger root extract, birch extract, horsetail extract, horseshoe extract, hawthorn extract, elderberry extract, cereal Achillea millefolium extract, Atlantic mint extract, sage extract, mallow extract, senkyu extract, assembly extract, soybean extract, taisou extract, fermented soybean extract, thyme extract, tea extract, clove extract, chigaya extract, chimpi extract, evening primrose extract, cinnamon extract, terminaria Extract, Toki Extract, Toki-Senka Extract, Tonin Extract, Spruce Extract, Dokudami Extract, Tomato Extract, Natto Extract, Carrot Extract, Garlic Extract, Novara Extract, Hibiscus Extract, Bacmond Extract, Parsley Extract, Honey, Banana Flower Extract, Hamamelis Extract , Parietalia extract, toad extract, bisabolol, loquat extract, Japanese dandelion extract, Japanese quince extract, Japanese cherry extract, butcher bloom extract Grape extract Examples include Yuzu extract, Yakuinin extract, Artemisia extract, Lavender extract, Apple extract, Lychee extract, Lettuce extract, Lemon extract, Astragalus extract, Rose extract, Rosemary extract, Roman chamomile extract, Royal jelly extract and the like.

Biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membranes, amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidonecarboxylate , Moisturizing ingredients such as polypeptides such as betaine, whey, trimethylglycine, lysine / arginine condensate, oily ingredients such as sphingolipid, ceramide, phytosphingosine, cholesterol, cholesterol derivatives, phospholipids, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, hydrocortisone, tea tree oil and other anti-inflammatory agents, vitamin A and its derivatives, vitamin B2 and its derivatives, vitamin B6 and its Derivatives, vitamin C and its derivatives, vitamin D and its derivatives, vitamin E and its derivatives, vitamins such as calcium pantothenate, biotin, nicotinamide, allantoin, diisopropylamine dichloroacetate, 4-aminomethylcyclohexanecarboxylic acid, etc. Active ingredients, tocopherols, carotenoids, flavonoids, tannins, lignans, saponins and other antioxidants, α-hydroxy acids, β-hydroxy acids and other cell activators, γ-oryzanol, vitamin E derivatives and other blood circulation promoters, retinol, Wound healing agents such as retinol derivatives, arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, glutathione and other whitening agents, cephalanthin, licorice extract, red pepper tincture, hinokitiol Iodinated garlic extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivative, calcium pantothenate, D-pantothenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropylmethyl Phenol, estradiol, ethinyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonyl acid vanillyl amide, nonanoic acid vanillyl amide, piroctone olamine, pentadecanoic acid glyceryl, L-menthol, mononitroguaiacol, resorcin , Γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormone, cantharis tincture, cyclosporine , Zinc pyrithione, hydrocortisone call Chizon, minoxidil, polyoxyethylene monostearate sorbitan, peppermint oil, and the like hair-growing agent such Sasanishiki extract.
(9) Examples of antioxidants

Sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolylbiguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxytoluene, ascorbyl stearate, palmitic acid Ascorbyl, octyl gallate, propyl gallate, carotenoids, flavonoids, tannins, lignans, saponins, plant extracts having an antioxidant effect such as apple extract and clove extract, and the like.
(10) Examples of solvents

Examples include purified water, ethanol, lower alcohol, ethers, LPG, fluorocarbon, N-methylpyrrolidone, fluoroalcohol, volatile linear silicone, and next-generation fluorocarbon.
The external preparation for skin according to the present invention can stably contain a zinc salt and / or zinc complex of amino acids over a long period of time, and a whitening effect and an anti-aging effect by the zinc salt and / or zinc complex of amino acids. Can be effectively demonstrated.
The external preparation for skin in the present invention can be suitably applied to cosmetics and the like.

  Application examples of the external preparation for skin of the present invention include makeup cosmetics such as foundation, white powder, eye shadow, eyeliner, eyebrow, teak, lipstick, nail color, emulsion, cream, lotion, calamine lotion, sunscreen agent , Suntan, after-shave lotion, pre-shave lotion, pack fee, anti-acne cosmetic, basic cosmetics such as essence, shampoo, rinse, conditioner, hair color, hair tonic, set agent, hair nourishing agent, permanent hair cosmetics , Body powder, deodorant, hair remover, soap, body shampoo, bathing agent, hand soap, perfume and the like.

  As the dosage form of the external preparation for skin of the present invention, conventionally known agents such as bilayer, water-in-oil emulsion, oil-in-water emulsion, gel, spray, mousse, oily, solid, sheet, powder, etc. A mold can be used.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the technical scope of the present invention is not limited to these examples.

(Examples 1-8, Comparative Examples 1-2)
(1) Method for confirming dissolution stability

  The following tests were conducted using a glycine zinc complex as the zinc salt or zinc complex of the amino acids of the present invention.

First, an aqueous solution (external preparation for skin) was prepared according to the formulation described in Table 1. The sample was allowed to stand in a thermostatic bath at 0 ° C., 25 ° C., and 50 ° C. for one month and then returned to room temperature to evaluate the dissolution stability of the aqueous solution over time. The stability evaluation was judged according to the following criteria.
Evaluation item ○: Complete dissolution x: Insoluble or crystal precipitation

（結果）表１より明らかなように、本発明品の実施例１〜８は水溶性の有機酸及び／又はその塩、アミノ酸及び／又はその塩を配合してグリシン亜鉛錯体水溶液を調製した試料で、グリシン亜鉛錯体の溶解性を一ヶ月間に渡って観察したが、各温度安定性に問題なかった。一方、比較例１〜２の水溶性の有機酸及び／又はその塩、アミノ酸及び／又はその塩、無添加及びリン酸を配合したグリシン亜鉛錯体水溶液は、不溶または結晶析出し安定性に問題があった。
（実施例９、比較例３）

(Results) As can be seen from Table 1, Examples 1 to 8 of the present invention were prepared by preparing a glycine zinc complex aqueous solution by blending a water-soluble organic acid and / or a salt thereof, an amino acid and / or a salt thereof. Thus, although the solubility of the glycine zinc complex was observed over one month, there was no problem in each temperature stability. On the other hand, the aqueous solution of glycine zinc complex containing the water-soluble organic acid and / or salt thereof, amino acid and / or salt thereof, additive-free and phosphoric acid in Comparative Examples 1 and 2 is insoluble or crystallized and has a problem in stability. there were.
(Example 9, Comparative Example 3)

UVB tolerance enhancement effect of HaCaT cells in each sample treatment of Zn (Gly) ₂ aqueous solution and Zn (Gly) ₂ citric acid added aqueous solution (1) Purpose

A complex made of Zn and the amino acid glycine, Zn (Gly) ₂ , has already been confirmed to have an enhancement of the antioxidant ability of skin cells and an inhibitory action on the production of melanin due to the induction of metallothionein, an intracellular antioxidant. ing. However, since Zn (Gly) ₂ has low solubility in water, it is difficult to blend it into a preparation or the like. To improve the solubility of Zn (Gly) _2, because it was found to be useful additives for dissolution agent such as citric acid from Example 1-8, the original Zn (Gly) ₂ by citrated In order to evaluate the effect on the whitening effect and anti-aging effect, which are functions of the ceramide, a UVB resistance test using HaCaT cells was performed, and the effects in the citrate-free and added systems were compared.
(2) Method

Test sample: Zn (Gly) ₂ aqueous solution (Comparative Example 3)
Zn (Gly) ₂ citric acid added aqueous solution (Example 9)

UVB resistance test

HaCaT human keratinocytes were seeded in a 96-well microplate using 5% FBS-DMEM (medium) so as to be almost confluent. 24 hours after sowing, the medium was replaced with a medium containing a sample having a predetermined concentration, and further cultured for 24 hours. After the sample treatment, the medium was replaced with Hank's equilibration buffer (Ca ²⁺ , Mg ²⁺ free; HBS (−)), and UVB with a Toshiba FL-SE lamp as the light source was changed to an energy amount of 15 mJ / cm ^2. The cells were irradiated. UVB non-irradiated control cells were covered with aluminum foil to shield UVB. Unirradiated cells were covered with aluminum foil to shield UVB. After the irradiation, HBS (−) was replaced with the medium again and further cultured for 24 hours. Cell viability was assessed with a neutral red (NR) assay. Measure the absorbance at 550 nm of a cell lysate prepared by adding 30% ethanol-containing 0.1N HCl solution after culturing in 20? G / mL NR-containing medium for 2 hours and taking up the live cells. Determined by The cell viability was expressed as a percentage with the absorbance of control cells (UVB non-irradiated cells) as 100. Statistical processing was performed using the Student t test.

統計処理：Ｓｔｕｄｅｎｔ'ｓ ｔ−ｔｅｓｔにて未処理コントロールに対する有意差を確認した。（＊ ｐ<０．０５， ＊＊ ｐ< ０．０１）
（結果）表２よりＺｎ（Ｇｌｙ）_２、Ｚｎ（Ｇｌｙ）_２＋クエン酸はともに１２．５ ?ＭよりＵＶＢ耐性能の有意な増加が認められた。上記結果より、Ｚｎ（Ｇｌｙ）_２の効能（ＵＶＢ耐性に関する増強作用）において、クエン酸添加による影響はない事が証明された。
（結論）表１、表２よりアミノ酸類の亜鉛塩及び／又は亜鉛錯体を皮膚外用剤中でも結晶化しない、皮膚に対する浸透性及び細胞内への取り込みの効率が高く、皮膚細胞のメタロチオネイン産生を誘導する効果を失わず、安定に配合することが出来る事が証明された。以上の結果から皮膚に対する浸透性及び細胞内への取り込みの効率が高く、美白効果、抗老化効果が充分である化粧料等の皮膚外用剤が開発可能である事が示唆された。

Statistical processing: Significant difference from untreated control was confirmed by Student's t-test. (* P <0.05, ** p <0.01)
(Results) From Table 2, a significant increase in UVB resistance was observed for both Zn (Gly) ₂ and Zn (Gly) ₂ + citric acid from 12.5? M. From the above results, it was proved that there was no influence by addition of citric acid on the efficacy of Zn (Gly) ₂ (enhancement effect on UVB resistance).
(Conclusion) Tables 1 and 2 show that zinc salts of amino acids and / or zinc complexes are not crystallized even in topical skin preparations, have high skin permeability and high efficiency of uptake into cells, and induce metallothionein production in skin cells. It has been proved that it can be blended stably without losing the effect. From the above results, it was suggested that it is possible to develop a skin external preparation such as cosmetics having high permeability to the skin and uptake into cells and sufficient whitening effect and anti-aging effect.

［調製方法］
Ａを４０℃で、Ｂ、Ｃを室温で均一に溶解する。Ａを攪拌しながらＢ、Ｃ、Ｄの順に添加し、均一になるまで攪拌し調製を終了。 Next, application examples (Examples 10 to 15) of the external preparation for skin such as cosmetics of the present invention will be shown.
(Example 10) Lotion

[Preparation method]
A is dissolved at 40 ° C., and B and C are uniformly dissolved at room temperature. While stirring A, add B, C, and D in this order, stir until uniform, and finish preparation.

［調製方法］
Ｂを４０℃で、Ａ、Ｃを室温で均一に溶解。Ａを通常攪拌しながらＢ、Ｃ、Ｄを加え、均一になるまで攪拌し調製を終了。 (Example 11) Essence

[Preparation method]
Dissolve B and B uniformly at 40 ° C and room temperature. Add B, C, and D while stirring A normally, and stir until uniform to complete the preparation.

［調製方法］
Ａ、Ｂを８０℃、Ｃ、Ｄ、Ｅを室温で均一に溶解。８０℃でＡをホモミキサーで攪拌しながらＢを加え乳化した後、通常攪拌しながら冷却。４０℃以下、好ましくは３５℃以下でＣ、Ｄ、Ｅの順に加えた。均一になるまで攪拌し調製を終了。 (Example 12) Night cream

[Preparation method]
A and B are uniformly dissolved at 80 ° C. and C, D and E are uniformly dissolved at room temperature. While stirring A with a homomixer at 80 ° C. and adding B, the mixture is emulsified and then cooled with normal stirring. C, D and E were added in this order at 40 ° C. or lower, preferably 35 ° C. or lower. Stir until homogeneous and finish preparation.

［調製方法］
Ａを秤量後、室温でＮＩＫＫＯＬ レシノール Ｓ−１０を均一に分散させてからＡ、Ｂを８０℃に加熱溶解。８０℃でＡをホモミキサーで攪拌しながらＢを加え乳化した後、通常攪拌しながら冷却。４０℃以下、好ましくは３５℃以下でＣ、Ｄの順に加え、均一になるまで攪拌し調製を終了。 (Example 13) Cream

[Preparation method]
After A was weighed, NIKKOL Resinol S-10 was uniformly dispersed at room temperature, and then A and B were heated and dissolved at 80 ° C. While stirring A with a homomixer at 80 ° C. and adding B, the mixture is emulsified and then cooled with normal stirring. Add C and D in this order at 40 ° C or lower, preferably 35 ° C or lower, and stir until uniform to complete the preparation.

［調製方法］
Ａを８０℃で均一に溶解し、室温まで冷却。Ｂをホモミキサーで撹拌均一後、Ａを加えホモミキサーで分散。ホモミキサーで撹拌しながらＣを加え乳化し、調製を終了。 (Example 14) Sunscreen

[Preparation method]
A is uniformly dissolved at 80 ° C. and cooled to room temperature. After stirring B with a homomixer, add A and disperse with a homomixer. C is added and emulsified with stirring with a homomixer to complete the preparation.

［調製方法］
Ａを秤量後、室温でＮＩＫＫＯＬ レシノール Ｓ−１０を均一に分散させてからＡ、Ｂを８０℃に加熱溶解。８０℃でＡをホモミキサーで攪拌しながらＢを加え乳化した後、通常攪拌しながら冷却。４０℃以下、好ましくは３５℃以下でＣ、Ｄの順に加え、均一になるまで攪拌し調製を終了。 (Example 15) Day cream

[Preparation method]
After A was weighed, NIKKOL Resinol S-10 was uniformly dispersed at room temperature, and then A and B were heated and dissolved at 80 ° C. While stirring A with a homomixer at 80 ° C. and adding B, the mixture is emulsified and then cooled with normal stirring. Add C and D in this order at 40 ° C or lower, preferably 35 ° C or lower, and stir until uniform to complete the preparation.

    All of the external preparations for skin of Examples 10 to 15 had good dissolution stability, and as a result of conducting an actual use test with continuous use for one month, it was confirmed that the whitening effect and anti-aging effect were sufficient.

  INDUSTRIAL APPLICATION This invention can mix | blend the zinc salt and / or zinc complex of amino acids stably with a skin external preparation, and can exhibit the whitening effect and the anti-aging effect effectively. Furthermore, an external preparation for skin containing a zinc salt of amino acids and / or a zinc complex can be provided as a product having no problem in temperature stability over a long period of time.

Claims (2)

A skin external preparation containing the following (A) and (B) and / or (C), wherein the blending mass ratio of (A) / {(B) + (C)} is 0.02 to 3 A topical skin preparation characterized by being.
(A) zinc salts of glycine and / or zinc complex (B) citric acid glycine, malic acid, one or more water-soluble organic acid and / or its salt selected from the group consisting of ascorbic acid ( C) One or more amino acids selected from the group consisting of proline, hydroxyproline, lysine hydrochloride, DL-serine, threonine, alanine and L-arginine and / or a salt thereof The external preparation for skin according to claim 1, which is a cosmetic.