JP2001011043A - Stabilized amino acid containing sulfur or its derivative and composition for external use containing them - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new compound having a reducing activity, an anti- oxidation activity, a melanin production-inhibiting activity, etc., also having less bad smelling and excellent in water solubility, stability with time, etc. SOLUTION: This stabilized amino acid containing sulfur is a compound of the formula [R1 is any one of SSO3R4 [R4 is H, a (substituted) alkyl, an alkali metal or an alkaline earth metal], SO2SH, SO2X (X is H, an alkali metal or an alkaline earth metal); R2 is H, a (substituted) alkyl, COOR7 [R7 is a (substituted)alkyl]; R3 is a polyhydroxyalkyl group joined by carbonyl or methylene group; (n) is 1,2}, e.g. N-D-gluconoyl-L-cysteine methyl ester. The compound of the formula is obtained e.g. by reacting methionine, cysteine or a derivative having cysteine with a carboxylic anhydride such as glucono-1,5-lactone having a group corresponding to the R3 in the formula in a usual method, performing de-blocking reaction and a conversion reaction of its functional group, etc., as necessary.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to stabilized sulfur-containing amino acids or derivatives thereof, and an external preparation composition containing them, and more particularly to an unstable aqueous solution which is unstable in an aqueous solution and deodorizes when decomposed. Sulfur-containing amino acids emitting water-soluble amino acids or derivatives thereof, without impairing the water solubility, as well as beauty liquids using them, cosmetics such as hair, or suitable for skin external preparations External preparation composition.

[0002]

2. Description of the Related Art It has been known that sulfur-containing amino acids represented by cysteine, methionine and the like and derivatives thereof have a reducing action, an antioxidant action and various physiologically active actions. For example, cysteine has been used as a permanent wave treating agent due to its reducing power. N-acetylcysteine (NAC) has been used for therapeutic purposes against acetaminophen overdose, and NAC has mucolytic properties and is used as a resting eye drop for dry eye syndrome. Have been.

JP-A-5-301811 discloses that peptides containing cystine or cysteine disulfide have a melanin production-suppressing action and a whitening effect, and JP-A-6-34579.
No. 7 discloses that a peptide containing cysteine can be an active ingredient of a lipid peroxide decomposition accelerator, a lipid peroxide inhibitor, an antioxidant, a melanin inhibitor and a skin cosmetic.

However, most of these sulfur-containing amino acids and their derivatives are unstable in aqueous solutions,
It has been known that decomposition, discoloration, precipitation, and the like are caused in a composition containing these, and a peculiar odor is emitted. Furthermore, among these, there is a problem in that it is often difficult to mix them into products, for example, some of the compounds themselves emit a bad smell. Compounds such as cystine, which are relatively stable to oxidation, have low water solubility and are difficult to formulate. On the other hand, as a method for stabilizing these sulfur-containing amino acids, for example, a method such as esterification with a long-chain alcohol can be considered. In this case, the introduction of a hydrophobic moiety significantly impairs the water solubility. There are issues.

[0005]

SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned conventional problems, and is intended to solve the problem. The present invention does not have a bad odor, is sufficiently stable and decomposes in an external preparation composition. It is an object of the present invention to provide a stabilized sulfur-containing amino acid or a derivative thereof, which does not emit water and has good water solubility, and an external preparation composition containing the same.

[0006]

Means for Solving the Problems The present inventors have conducted intensive searches to solve the above-mentioned conventional problems, and as a result, have found that sulfur-containing amino acids having a specific group derived from a saccharide or a derivative thereof can be obtained. The present inventors have found that the above-mentioned stabilized sulfur-containing amino acids or derivatives thereof and a composition for external use can be obtained, and have completed the present invention. That is,
The present invention resides in the following (1) and (2). (1) A stabilized sulfur-containing amino acid or a derivative thereof comprising at least one compound represented by the following general formula (I).

Embedded image (2) An external preparation composition comprising the sulfur-containing amino acids or derivatives thereof described in (1) above.

[0007]

Embodiments of the present invention will be described below in detail. The stabilized sulfur-containing amino acids or derivatives thereof (hereinafter, simply referred to as “sulfur-containing amino acids”) of the present invention are characterized by comprising at least one compound represented by the following general formula (I). Is what you do.

Embedded image

In the present invention, the sulfur-containing amino acids represented by the general formula (I) include a reducing action, an antioxidant action, various physiologically active actions, a melanin production inhibitory action, a peroxidative action, which the sulfur-containing amino acids have. Lipid decomposition promoting action, without inhibiting any properties such as lipid peroxide suppressing action, decomposition in a system in which the sulfur-containing amino acids are dissolved, discoloration, precipitation, etc., and,
Unique odors can be prevented to the extent that there is no practical problem,
In addition, since there are very few restrictions on the composition of the composition, the compound is excellent in water solubility and stability over time (storage stability), and is a stabilized sulfur-containing amino acid that can be easily formulated.

The sulfur-containing amino acids represented by the above general formula (I) in the present invention include, for example, N-gluconoyl-cysteine, N, N'-digluconoyl-cystine, 2-carboxy-2-gluconoylamino Ethanesulfinic acid, 2-carboxy-2-gluconoylaminoethanethiosulfonic acid, N- (2,3,4,5,6-pentahydroxyhexyl) methionine, N- (2,3,
4,5,6-pentahydroxyhexyl) cysteine,
N, N'-di (2,3,4,5,6-pentahydroxyhexyl) cystine, 2-carboxy-2- (2,3,
4,5,6-pentahydroxyhexylamino) ethanesulfinic acid, 2-carboxy-2- (2,3,4,
5,6-pentahydroxyhexylamino) ethanethiosulfonic acid and ester compounds thereof. Among these, from the viewpoints of raw material supply, ease of production, cost, and the like, in particular, ND-gluconoyl-L-cysteine methyl ester, ND-gluconoyl-L-cysteine, ND-gluconoyl-L- Methionine methyl ester, ND-gluconoyl-L-methionine,
N, N'-di (D-gluconoyl) -L-cystine dimethyl ester, N, N'-di (D-gluconoyl) -L
-Cystine, 2-carboxy-2-gluconoylaminoethanesulfinic acid, 2-methylcarboxy-2-gluconoylaminoethanesulfinic acid, 2-carboxy-
2-gluconoylaminoethanethiosulfonic acid, 2-methylcarboxy-2-gluconoylaminoethanethiosulfonic acid, N- (2,3,4,5,6-pentahydroxyhexyl) -L-methionine, N- ( 2,3,4
5,6-pentahydroxyhexyl) -L-methionine methyl ester, N- (2,3,4,5,6-pentahydroxyhexyl) cysteine, N- (2,3,4,
5,6-pentahydroxyhexyl) cysteine methyl ester, N, N'-di (2,3,4,5,6-pentahydroxyhexyl) -L-cystine, N, N'-di (2,3,4 , 5,6-pentahydroxyhexyl)-
L-cystine dimethyl ester, 2-carboxy-2-
(2,3,4,5,6-pentahydroxyhexylamino) ethanesulfinic acid, 2-methylcarboxy-2-
(2,3,4,5,6-pentahydroxyhexylamino) ethanesulfinic acid, 2-carboxy-2- (2
3,4,5,6-pentahydroxyhexylamino) ethanethiosulfonic acid, 2-methylcarboxy-2-
(2,3,4,5,6-pentahydroxyhexylamino) ethanethiosulfonic acid is preferred. In the present invention, the compounds to be the above-mentioned various sulfur-containing amino acids are used alone (1
Species) or a combination of two or more kinds.

Although most of the compounds represented by the above formula (I) are novel compounds, only a few compounds, for example, N-1- (D-mannicyl)-
D, L-methionine and the like are described in J. Bacteriol., 158 (2), 650-65.
8 (1984) .ND-gluconoyl-L-methionine and the like are described in Z. Naturforsch.,
B: A synthesis example is reported in Chem. Sci., 50 (4), 515-523 (1995). However, these reports
It has been made as one of a series of amino acid derivatives, and the reported compound is excellent in water solubility and stability over time (storage stability), and is also a stabilized sulfur-containing amino acid which can be easily formulated. Nothing is described or suggested in each of the above documents, and no recognition or motivation is given.

In the present invention, the sulfur-containing amino acids represented by the above general formula (I) can be produced, for example, by the following synthesis method. That is, a derivative having methionine, cystine, cysteine or a protective group thereof and a glucono-containing derivative having a group corresponding to R ₃ in the general formula (I).
Reaction with a carboxylic anhydride such as 1,5-lactone by a conventional method, and if necessary, a method such as deprotection or functional group conversion reaction, or methionine, cystine, cysteine or a protective group thereof. Having the above general formula (I)
A Schiff base can be produced from an aldose having a group corresponding to R ₃ therein, and then reduced, and if necessary, can be produced by a method such as deprotection or functional group conversion reaction ( This will be described in detail in a production example described later).
All of the compounds used in these syntheses are commercially available at low cost, and the reactions involved in the synthesis are very common, so that they are inexpensive and efficient compared to conventionally used compounds. What you can get. Further, each of the compounds represented by the general formula (I) has a polyhydroxyalkyl group derived from a sugar as well as a powder, a tablet and the like, and has high water solubility, so that an external preparation for an aqueous solution can be obtained. It can be easily incorporated into the composition.

The external preparation composition of the present invention comprises at least one compound represented by the above general formula (I) [alone (1
Species) or two or more types thereof, for example, in a formulation of cosmetics, quasi-drugs, pharmaceuticals, etc., containing a compound represented by the above general formula (I). is there. The compounding amount of the compound represented by the above general formula (I) in these preparations should be appropriately determined according to the use and the type or amount of the multiple components to be mixed at the same time, and should not be unconditionally specified. However, usually, it is preferable to mix so as to be 0.0001 to 5% by weight (hereinafter, simply referred to as “%”) with respect to the total amount of the external preparation composition,
More preferably, it is 0.0025 to 2.0%. Although many types of compounds having the structure of the general formula (I) are exemplified, it is of course possible to independently compound each of them in the external preparation composition of the present invention. Further, two or more of them can be appropriately combined and blended. In this case, the kind of the compound and the blending ratio are arbitrary and are not particularly limited.

When the external preparation composition of the present invention is used, for example, as an external preparation for skin, in addition to the components of the above general formula (I), oil, water (purified water, ion-exchanged water) and surfactant , Humectants, lower alcohols, thickeners, known antioxidants, chelating agents, pH adjusters, preservatives, fragrances, pigments, powder components, UV absorbers, UV scattering agents, vitamins, amino acids, and other effective agents Raw materials that are usually used for external preparations for skin, such as components, plant extracts, and high molecular substances, can be appropriately added in amounts that do not impair the effects of the present invention. Hereinafter, the names of the raw materials and the like of each component will be specifically described.

Examples of oils include olive oil, jojoba oil, castor oil, cocoa butter, camellia oil, coconut oil, wood wax, grape seed oil, avocado oil, mink oil, egg yolk oil, hardened oil, evening primrose oil, turtle oil, Macadamia nut oil, corn oil, rapeseed oil, sesame oil, persic oil, wheat germ oil, sasanqua oil, linseed oil, safflower oil, cottonseed oil,
Eno oil, soybean oil, peanut oil, teaseed oil, kaya oil, rice bran oil, cinnamon oil, Japanese kiri oil, germ oil, triglycerin, glycerin trioctanoate, glycerin triisopalmitate, horse oil, hydrogenated coconut oil, palm Oils, beef tallow, sheep tallow, hardened tallow, palm kernel oil, lard, beef tallow, mokuro tachibana oil, beef foot oil, hardened castor oil, etc., whale wax, beeswax, lanolin, carnauba wax, candelilla wax Cotton wax, Bayberry wax, Ibota wax, Montan wax, Monta wax, Nuka wax, Kapok wax, lanolin acetate, liquid lanolin, sugar cane wax, lanolin fatty acid isopropyl, hexyl laurate, reduced lanolin, jojoba wax, hard lanolin, shellac wax, polyoxyethylene (POE) Lanolin alcohol ether, POE lanolin alcohol acetate, POE Sterol ether, lanolin fatty acid polyethylene glycol - le, waxes such as POE hydrogenated lanolin alcohol ether, liquid paraffin, ceresin, squalane, microcrystalline wax,
Hydrocarbons such as paraffin wax, petrolatum, ozokerite, squalene, pristane, paraffin, stearic acid, oleic acid, lauric acid, myristic acid, isostearic acid, oleic acid, palmitic acid, behenic acid, 12 -Hydroquinstearic acid, undecylenic acid, tolic acid, linoleic acid, linoleic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DH
Fatty acids such as A), cetanol, stearyl alcohol, lanolyl alcohol, octyldodecanol, hexyldecanol, lauryl alcohol, cetyl alcohol, benzyl alcohol, myristyl alcohol, oleyl alcohol, cetostearyl alcohol, monostearylglycerin ether ( Butyl alcohol), 2-
Alcohols such as decyltetradecinol, cholesterol, phytosterol, and isostearyl alcohol;
Isopropyl myristate, butyl stearate, isopropyl palmitate, octyl dodecyl myristate, cholesterol oleate, cetyl octoate, octyl dodecyl myristate, hexyl laurate, myristyl myristate, decyl oleate, hexyl decyl dimethyl octanoate, cetyl lactate , Myristyl lactate,
Lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 1,2-hydroxystearate, ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid ester, N-alkyl glycol monoisostearate, neopentyl glycol socaprate, apple Diisostearyl acid, glycerin di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexylate, trimethylolpropane triisostearate, pentaneerythritol tetra-2-ethylhexanoate, glycerin tri-2-ethylhexylate, triglycol Trimethylolpropane isostearate, cetyl-2-ethylhexanoate,
2-ethylhexyl palmitate, glyceryl trimyristate, glyceride tri-2-heptylundecanoate, methyl ester of castor oil fatty acid, oleic oil, cetostearyl alcohol, acetoglyceride,
2-heptylundecyl palmitate, diisobutyl adipate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, di-2-ethylhexyl sebacate, 2-myristate Esters such as hexyldecyl, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, ethyl acetate, butyl acetate, amyl acetate, and triethyl citrate.

Examples of the surfactant include sodium cetyl sulfate, POE lauryl ether phosphate, sodium lauryl phosphate, triethanolamine palmitate, sodium N-acylglutamate, soap base, sodium laurate, stearic acid Sodium, fatty acid soaps such as sodium palmitate, sodium rawyl sulfate, lauryl sulfate K, POE lauryl sulfate triethanolamine, POE sodium lauryl sulfate, lauroyl sarcosine sodium, sodium N-myristoyl-N-methyltaurine, coconut fatty acid methyl tauride Sodium, lauryl methyl tauride sodium, POE sodium oleyl ether phosphate, POE stearyl ether phosphoric acid, di-2-ethylhexyl sulfo sodium Sodium acid, mono-lauroyl mono- ethanolate - Ruamido POE sulfosuccinate,
Sulfosuccinates such as sodium lauryl polypropylene glycol sulfosuccinate, sodium linear dodecylbenzenesulfonate, triethanolamine linear dodecylbenzenesulfonate, linear dodecylbenzenesulfonic acid, monosodium N-lauroylglutamate, disodium N-stearoylglutamate, N-
Myristoyl-L-glutamate monosodium, hydrogenated coconut oil fatty acid sodium glycerin sulfate, funnel oil, P
OE alkyl ether carboxylic acid, POE alkyl allyl ether carboxylate, α-olefin sulfonate, higher fatty acid ester sulfonate, secondary alcohol sulfate, higher fatty acid alkylolamide sulfate, lauroyl monoethanolamide succinic acid Sodium, N-palmitoylaspartic acid ditriethanolamine, anionic surfactant such as sodium caseinate, stearyl dimethylbenzyl ammonium chloride,
Alkyltrimethylammonium salts such as stearyltrimethylammonium chloride and lauryltrimethylammonium chloride, distearyldimethylammonium dialkyldimethylammonium salt, poly (N, N'-
Dimethyl-3,5-methylenepiperidinium), alkylpyridinium salts such as cetylpyridinium chloride, alkyl quaternary ammonium salts, alkyldimethylbenzylammonium salts, alkylisoquinolinium salts, dialkylmorphonium salts, POE alkylamines, alkyl Amine salts, polyamine fatty acid derivatives, amyl alcohol fatty acid derivatives, cationic surfactants such as benzalkonium chloride, benzethonium chloride, alkylaminoethylene glycine chloride solution, lecithin, 2-undecyl-N- (hydroxyethylcarboxymethyl) -2- Imidazoline sodium, 2-cocoyl-2-imitazolinium hydroxide-1-carboxyethyloxy disodium salt, 2-
Amphoteric surfactants such as heptadecyl-N-carboxymethyl-N-hydroquinethylimidazolinium betaine, lauryl dimethylaminoacetic acid betaine, alkyl betaine, amido betaine, sulfobetaine, sucrose fatty acid ester, polyethylene monostearate Glycol,
POE coconut fatty acid monoethanolamide, POE polyoxypropylene glycol, POE castor oil, POE lanolin, sorbitan monostearate, POE sorbitan monopalmitate, sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmi Tate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate, glycerin mono-cottonseed oil fatty acid glycerin,
Glycerin monoerucate, glycerin sesquioleate, α, α'-oleic acid glyceryl pyroglutamate, glyceryl monostearate malate, glyceryl monostearate, propylene glycol monostearate, hydrogenated castor oil derivative, glycerin alkyl ether, POE / methyl Polysiloxane copolymer, POE sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, POE-
Sorbitan tetraoleate, POE-Sorbit monolaurate, POE-Sorbit monooleate, PO
E oleyl ether, POE-sorbit pentaoleate, POE-sorbit monostearate, POE-
Glycerin monostearate, POE-glycerin monoisostearate, POE-glycerin triisostearate, POE monooleate, POE distearate, POE monodioleate, ethylene glycol cysteate, POE lauryl ether, POE stearyl ether, POE behenyl ether, POE2 -POE alkyl ethers such as octyl dodecyl ether, POE cholestanol ether, POE octyl phenyl ether, POE nonyl phenyl ether, POE dinonyl phenyl ether, pluronic, POE polyoxypropylene cetyl ether, POE polyoxypropylene 2-decyl tetra Decyl ether, POE / polyoxypropylene monobutyl ether, POE / polyoxypropylene water Lanolin, POE · polyoxypropylene glycerine E - ether, Tetronic, POE hardened castor oil, POE hydrogenated castor oil monoisostearate, POE hydrogenated castor oil triisostearate, POE
Hydrogenated human oil monovilogultamic acid monoisostearic acid diester, POE hydrogenated human oil maleic acid, POE
Sorbitol beeswax, coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid impropanolamide, POE propylene glycol fatty acid ester, POE alkylamine, POE fatty acid amide,
Examples include nonionic surfactants such as POE nonylphenylformaldehyde condensate, alkylethoxydimethylamine oxide, and trioleyl phosphoric acid.

Examples of humectants include glycerin,
1,3-butylene glycol, propylene glycol,
Polyhydric alcohols such as sorbitol, polyethylene glycol, dipropylene glycol, hexylene glycol, xylitol, maltitol, NMF components such as amino acids, sodium lactate, sodium pyrrolidone carboxylate, hyaluronic acid, atelocollagen, short-chain soluble collagen, mucopolysaccharide , Mucoitin sulfate, chondroitin sulfate, etc., water-soluble high molecular substances, common rose extract, European millet extract, melilot extract, erythronic acid, cholesteryl-12-hydroxystearate, sodium lactate, bile salts, d, l-pyrrolidone carboxylate, diglycerin (EO) PO adduct and the like.

Examples of the lower alcohol include ethanol, isopropanol and the like. As the thickener, for example, sodium alginate, xanthan gum,
Aluminum silicate, quince seed extract, tragacanth gum, starch, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, soluble starch, cationized cellulose, carboxyvinyl polymer, polyvinyl alcohol arabic gum, power ragginan, power ryagum, carob gum, casein, dextrin, gelatin, Sodium pectate, sodium alginate, ethylcellulose, hydroxypropylcellulose, PVM, PVP, sodium polyacrylate, low-strength bean gum, guar gum, evening malint gum, dialkyldimethylammonium sulfate cellulose, aluminum magnesium silicate, bentonite, hectorite, etc. Can be

Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, ascorbic acid and derivatives thereof. Examples of the chelating agent include edetic acid, ethanehydroxyphosphate, pyrophosphoric acid, hexametaphosphoric acid, cisan, tartaric acid, glucuronic acid, and physiologically acceptable salts thereof. Examples of the pH adjuster include sodium hydroxide, triethanolamine, citric acid, sodium citrate, boric acid, borax, sodium monohydrogen phosphate, and the like. Examples of preservatives include methyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, dehydrosuccin, salicylic acid, benzoic acid, sorbic acid, benzalkonium chloride and the like.

Examples of the fragrance include hydrocarbons such as aliphatic hydrocarbons, terpene hydrocarbons and aromatic hydrocarbons, alcohols such as aliphatic alcohols, terpene alcohols and aromatic alcohols, aliphatic ethers and aromatic ethers. Oxides such as ethers, aliphatic oxides and terpenes, aldehydes such as aliphatic aldehydes, terpene aldehydes, hydrogenated aromatic aldehydes, thioaldehydes, aromatic aldehydes, aliphatic ketones, terpene ketones, hydrogen Aromatic ketone, aliphatic cyclic ketone,
Non-benzene aromatic ketones, ketones such as aromatic ketones, acetals, ketals, phenols, phenol ethers, fatty acids, terpene carboxylic acids, hydrogenated aromatic carboxylic acids, acids such as aromatic carboxylic acids, Lactones such as acid amides, aliphatic lactones, macrocyclic lactones, terpene lactones, hydrogenated aromatic lactones, aromatic lactones, aliphatic esters, furan carboxylic acid esters, aliphatic cyclic carboxylic acid esters, cyclohexyl carboxylic acid Synthetic fragrances such as esters such as acid esters, terpene carboxylic esters and aromatic carboxylic esters, nitrogen-containing compounds such as nitromusks, nitriles, amines, pyridines, quinolines, pyrroles and indoles; and from animals and plants Including natural flavors, natural flavors and / or synthetic flavors One or flavoring may be used a mixture of two or more. For example, "Synthetic Fragrance Chemistry and Product Knowledge" by Motoichi Indo, published by Kagaku Kogyo Nippo, 1996, 1
969 MONTCLAIR, N.M. J. Published Steffe
N Arctander, "Perfume and
Flavor Chemicals "and the like. The main flavor names are shown below. Aldehyde C6
~ C12, anisaldehyde, acetal R, acetophenone, acetylsedrene, adoxal, allyl amyl glycolate, allyl cyclohexanepropionate, alpha damascon, beta damascon, delta damascon, ambrette lid, ambroxane, amylcinamic Aldehydes, amylcinamic aldehyde dimethyl acetal, amyl valerinate, amyl salicylate, isoamyl acetate, isoamyl salicylate, aurantiol, acetyljugenol,
Bacdanol, benzyl acetate, benzyl alcohol, benzyl salicylate, bergamyl acetate,
Bornyl acetate, butyl butyrate, p-tert-butyl cyclohexanol, p-tert-butyl cyclohexyl acetate, ortho-tert-butyl cyclohexanol, benzaldehyde, benzyl formate, caryophyllene, kashmelan, carvone, cedroambar, cedrill acetate, cedrol , Celestrid, Cinamic Alcohol, Cinamic Aldehyde, Cis Jasmon, Citral, Citral Dimethyl Acetal, Citrasal, Citronellal, Citronellol, Citronellyl Acetate, Citronellyl Formate, Citronellyl Nitrile, Cyclacet, Cyclamenaldehyde, Cyclaprop, Caron , Coumarin, cinnamyl acetate, delta C6 ~
C13 lactone, dimethylbenzylcarbinol, dihydrojasmon, dihydrolinalool, dihydromyrcenol, dimetol, dimyrcetol, diphenyloxide, ethylvanillin, jugenol, fluitate,
Fentyl alcohol, phenylethyl phenyl acetate, garaki solid, gamma C6-13 lactone, geraniol, geranyl acetate, geranyl formate, geranyl nitrile, hedion, helional, heliotropin, cis-3-hexenol, cis-
3-hexenyl acetate, cis-3-hexenyl salicylate, hexylcinnamic aldehyde, hexyl salicylate, hyacinth dimethyl acetal, hydrotropic alcohol, hydroxycitronellal, indole, ionone, isobornyl acetate,
Isocyclocitral, iso-E super, isoyugenol, isononyl acetate, isobutyl quinoline, jasmar, jasmolactone, jasmophylan, coabon, rigstral, lilial, lime oxide, limonene, linalool, linalool oxide, linalyl acetate, linalal, manzanate, Mayol, Mensanil acetate, Mensonate, Methyl anthranilate, Methyl eugenol, Menthol, Alpha methyl ionone, Beta methyl ionone, Gamma methyl ionone, Methyl isoyugenol, Methyl lavender ketone, Methyl salicylate, Muge aldehyde,
Mugor, Musk TM-II, Musk 781, Musk C1
4. Musk T, musk ketone, musk tibetin, musk moskene, mirac aldehyde, methyl phenyl acetate, nerol, neryl acetate, nopylacetate, nopyr alcohol, neobergamate, oak moss No.1, oribbon, oxyphenylon, paracre Diel methyl ether, pentalid, phenylethyl alcohol, phenylethyl acetate, alpha pinene, rubafuran, rosephenone, rose oxide,
Sandaroa, Sandera, Santa Rex, Styril Real Acetate, Styril Real Propionate, Terpineol, Terpinyl Acetate, Tetrahydrolinalool, Tetrahydrolinalyl Acetate, Tetrahydrogeraniol, Tetrahydrogeranyl Acetate, Tonalid, Tratheolide, Tripral, thymol, crocodile, veldox, yarayara, anise oil,
Bay oil, boad rose oil, cananga oil, cardamom oil,
Cassia oil, cedarwood oil, orange oil, mandarin oil, tangerine oil, basil oil, nutmeg oil, citronella oil, clove oil, coriander oil, elemi oil, eucalyptus oil, fennel oil, galbanum oil, geranium oil, hiba oil, cypress oil , Jasmine oil, lavandin oil, lavender oil, lemon oil, lemongrass oil, lime oil, neroli oil,
Oak moss oil, okotia oil, patchouli oil, peppermint oil, perilla oil, petitgren oil, pine oil, rose oil, rosemary oil, camphor oil, fragrance oil, clary sage oil,
Sandalwood oil, spearmint oil, spike lavender oil, star anise oil, thyme oil, tonka bean tincture, turpentine oil, crocodile bean tincture, vetiver oil, ylang-ylang oil, grapefruit oil, citron oil, benzoin, peruvian balsam, tolubal sam, Tuberose oil, musk tincture, castorium tincture, civet tincture, ambergris tincture. In addition, diethyl phthalate, dipropylene glycol, benzyl benzoate, isopropyl myristate, hercoline, or the like can be used as a solvent or a retaining agent for the fragrance. In addition, a fragrance | flavor is not limited to the fragrance | flavor of an Example.

Examples of pigments include titanium dioxide, zinc oxide, iron oxide (iron oxide), iron titanate, γ-iron oxide, yellow iron oxide, loess, black iron oxide, carbon black, lower titanium oxide, and mango violet. , Cobalt violet, chromium oxide, chromium hydroxide, cobalt titanate,
Ultramarine blue, navy blue, titanium oxide coated my strength, titanium oxide coated bismuth oxychloride, titanium oxide coated talc, colored titanium oxide coated my strength, bismuth oxychloride, fish scale foil, aluminum powder, power pepper powder, red 201, red 202 , Red No. 204,
Red 205, Red 220, Red 226, Red 22
No. 8, Red 405, Orange No. 203, Orange No. 204, Yellow No. 205, Red No. 401, Blue No. 404, Red No. 3
No. Red No. 104, Red No. 106, Red No. 227, Red No. 230, Red No. 401, Red No. 505, Orange 205
No. 4, Yellow No. 4, Yellow No. 5, Yellow No. 202, Yellow No. 203
No. 3, green No. 3, blue No. 1, chlorophyll, β-caroline, titanium yellow, carsamine, safflower red and the like.

Examples of the powder component include talc, carion, mica, sericite (sericite), muscovite, phlogopite,
Synthetic mica, mica, biotite, lithia mica, permiculite, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungstate, magnesium, silica, zeolite , Barium sulfate, calcined calcium sulfate, (baked gypsum), calcium carbonate, fluorapatite, hydroxyapatite, ceramic powder, metal soap (zinc myristate,
Calcium palmitate, aluminum stearate)
Boron nitride, polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene powder, copolymer resin powder of styrene and acrylic acid, benzoguanamine resin powder, polytetrafluoroethylene powder, cellulose powder, etc. Is mentioned.

Examples of the ultraviolet absorber include methyl anthranilate, homomenthyl / acetyl anthranilate, 2,4-dihydroxybenzophenone and 22-
Dihydroxy-4-methoxybenzophenone, 2,2 ′
-Dihydroxy-4,4'-dimethoxybenzophenone, 2,2'-4,4'-tetrahydroquinbenzophenone, 2-hydroxy-4-methoxybenzophenone,
2-hydroxy-4-methoxy-4'-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone,
-Ethylhexyl-4'-phenylbenzophenone-2
-Carboxylate, 2-hydroxy-4-n-octoxybenzophenone, 4-hydroxy-3-butoxybenzophenone, 2,2'-hydroxy-5-methylphenylbenzotriazole, 2- (2'-hydroxy-
5′-t-octylphenylbenzotriazole, 2-
(2′-hydroxy-5′-methylphenyl) benzotriazole, dianisoylmethane, 4-methoxy-4 ′
-T-butyldibenzoylmethane (parsol A), para-aminobenzoic acid, octyldimethylpara-aminobenzoic acid, para-aminobenzoic acid monoglycerin ester, N,
N-dipropoxyparaaminobenzoic acid ethyl ester,
N, N-diethoxyparaaminobenzoic acid ethyl ester, N, N-dimethylparaaminobenzoic acid ethyl ester, N, N-dimethylparaaminobenzoic acid butyl ester, N, N-dimethylparaaminobenzoic acid amyl ester, dipropylene glycol salicylate, Ethylene glycol salicylate, myristyl salicylate, methyl salicylate, amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate,
p-isopropanol phenyl salicylate, octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl-2,5-diisopropyl cinnamate, ethyl-24-diisopropyl cinnamate, methyl
2,4-diisopropylcinnamate, propyl-p-
Methoxy cinnamate, isopropylprop-p-methoxy cinnamate, isoamyl-p-methoxy cinnamate, octyl-p-methoxy cinnamate (2-ethylhexyl-p-methoxy cinnamate), 2-ethoxyethyl-p-methoxy cinnamate , Cyclohexyl-
p-methoxycinnamate, ethyl-α-cyano-β-
Phenylcinnamate, 2-ethylhexyl-α-cyano-β-phenylcinnamate, glyceryl mono-2-
Ethylhexanoyldiparamethoxycinnamate, octyl methoxycinnamate, 3-methyl-4- [methylbis (trimethylsiloxy) silyl] butyl 3,4,5-trimethoxycinnamate, mono-p-dimethoxycinnamate Ethyl ester, 3- (4'-methylbenzylidene)-
camphor derivatives such as d, l-forcenfa, 3-pendylidene-d, l-forcenfa, 5- (3,3-dimethyl-2-norbornylidene) -3-penten-2-one; urocanic acid, Urocanic acid ethyl ester, 2-
Phenyl-5-methylbenzoxazole, dibenzalazine and the like can be mentioned, and as the ultraviolet scattering agent, titanium oxide, kaolin, talc, carmine, zinc oxide, bentonite and the like can be mentioned.

Examples of vitamins include vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin F, vitamin K, vitamin P, vitamin K, vitamin P, vitamin U, carnitine, ferulic acid, γ- Oryzanol, α-lipoic acid, orotic acid and their components or derivatives, such as retinol acetate, riboflavin acetate, pyridoxine dioctanoate, L-ascorbic acid dipalmitate, L-ascorbic acid-2-sodium sulfate, L- Ascorbic acid phosphate, DL-tocopherol-L-ascorbic acid diester dipotassium phosphate, pantothenyl ethyl ether, D-pantothenyl alcohol, acetyl pantothenyl ethyl ether, ergocalciferol, cholecalciferol, nicotinic acid, Nicotinic acids such as nicotinamide and benzyl nicotinate; α-tocopherol,
Examples include tocopherol acetate, nicotinic acid-DL-α-tocopherol, DL-α-tocopherol succinate, biotin and the like.

Examples of the amino acid include glycine, alanine, valine, leucine, isoleucine, serine, threonine, phenylalanine, tyrosine, tryptophan, cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid, glutamic acid, arginine, histidine, lysine. And its derivatives.

Examples of the plant extract include oak extract, spinach extract, sicon extract, peony extract, assembly extract, birch oil extract,
Sage extract, loquat extract, carrot extract, aloe extract, mallow extract, iris extract, grape extract, yokuinin extract, loofah extract, lily extract, saffron extract, senkyu extract, ginger extract Extract components, hypericum extract components, ononis extract components, rosemary extract components, garlic extract components, capsicum extract components, chimneys, corns, and the like.

Other active ingredients include, for example, glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, anti-inflammatory agents such as hinokitiol, zinc oxide, allantoin, royal jelly, photosensitizers, cholesterol derivatives, and calf blood extracts. Activator, placental extract, glutathione, yuxita extract, whitening agents such as arbutin, nonylate valenylamide, nicotinic acid benzyl ester,
Nicotinic acid-β-butoxyethyl ester, capsaicin, gingerone, tincture tincture, itctamol, caffeine, yunic acid, α-borneol, tocopherol nicotinate, inositol hexanicotinate, cyclandate, cinnarizine, trazoline, acetylcholine, Blood circulation promoters such as verapamil, cepharanthin, and γ-oryzanol; and antiseborrheic agents such as sulfur and thiantol.

Examples of the high-molecular substances include arabia gum, tragacanth gum, galactan, guar gum, carob gum, kyaraya gum, carrageenan, pectin, agar, quince seed (quince), alge colloid (cassow extract), starch (rice, corn,
Potato, wheat), glycyrrhizic acid, xanthan gum, dextran, succinoglucan, pullulan,
Collagen, casein, albumin, gelatin, carboxymethyl starch, methylhydroxypropyl starch, methylcellulose, nitrocellulose, ethylcellulose, methylhydroxypropylcellulose, hydroxyethylcellulose, sodium cellulose sulfate, hydroxypropylcellulose, sodium carboxymethylcellulose (CMC), crystalline cellulose, Cellulose powder, sodium alginate, propylene glycol alginate, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl vilolidone, lipoxyvinyl polymer (Carbopol), alkyl-modified carboxyvinyl polymer, polyethylene glycol 2000,
POE polymers such as 000 and 6000, POE polyoxypropylene copolymer polymers, sodium polyacrylate, polyethyl acrylate, polyacrylamide,
Examples include polyethyleneimine, cationic polymer, pentonite, AlMg silicate (Vegum), laponite, hectorite, silicic anhydride, and the like.

The above-mentioned optional components blended in the external preparation composition of the present invention are not limited to these, and for example, extracts of animal and microbial origin can be added as appropriate.

The composition for external use of the present invention can be widely applied to cosmetics, pharmaceuticals, quasi-drugs, etc., and its dosage form is, for example, aqueous solution type, solubilizing type, emulsifying type, powder type. System, oil-liquid system, gel system, ointment system, aerosol system, water-liquid 2
It can take a wide range of dosage forms such as a layer system, a water-oil-powder three-layer system, and the like. That is, for cosmetics, face wash, lotion, milky lotion, cream, gel, essence (serum),
It is widely applicable in the form of packs, masks, hair tonics, hair lotions and the like in the various dosage forms described above.
In addition, makeup cosmetics can be widely applied to forms such as foundations, and pharmaceuticals or quasi-drugs can be widely applied to forms of various external solutions and ointments. These dosage forms and forms are not limited to those described above, and the dosage form and form are not particularly limited as long as they are the external preparation composition of the present invention. These external preparation compositions (products)
The compound can be produced by appropriately mixing at least one of the compounds represented by the general formula (I) and the above-mentioned optional components. Hereinafter, preparation examples of the external preparation composition will be individually described.

Specific preparation examples when the external preparation composition of the present invention is used as a skin cosmetic are shown in the following (1) to (5). (1) lotion and essence 0.1 to 5% of the compound represented by the general formula (I) is contained,
And, as optional components, alcohols 0 to 20%, surfactants 0 to 2%, humectants 2 to 15%, pH adjusters 0 to 3%,
Lotion and serum containing purified water balance, trace amounts of preservatives, 0% to trace amounts of pigment, and trace amounts of fragrance. (2) skin cream containing 0.1 to 5% of a compound represented by the general formula (I),
And an optional oil component of 10 to 70% and a surfactant of 2
Skin cream containing 7%, humectant 1-10%, pH adjuster 0-3%, purified water balance, trace amount of preservative, trace amount of fragrance. (3) Emulsion 0.1 to 5% of the compound represented by the general formula (I),
10 to 40% of oil as an optional component, and 0 alcohols
-15%, surfactant 1-5%, humectant 1-10%, thickener 0-2%, pH adjuster 0-3%, purified water balance,
Emulsion containing trace amounts of preservatives and trace amounts of perfume. (4) Packing agent containing 0.1 to 5% of the compound represented by the general formula (I),
And, as optional components, alcohols 2 to 10%, humectants 2 to 10%, inorganic powders 0 to 20%, film thickeners 10 to 20
%, Purified water balance, trace amount of preservative, trace amount of fragrance. (5) Gel agent containing 0.1 to 5% of the compound represented by the general formula (I),
And 0 to 10% of alcohols as optional components, humectant 2
~ 20%, thickener 1 ~ 20%, pH adjuster 0 ~ 30%,
Lotion and serum containing purified water balance, trace amounts of preservatives, 0% to trace amounts of pigment, and trace amounts of fragrance.

Further, when the external preparation composition of the present invention is used as a bathing agent, for example, sodium chloride, potassium iodide,
Ammonium chloride, sodium sulfate, sodium hydrogen carbonate, sodium carbonate, sodium sesquicarbonate, aluminum sulfate, potassium sulfide, potassium sulfate, boric acid, borax, silicic anhydride, metasilicic acid, sodium sulfite, phosphoric acid, sodium hydrogen phosphate, Inorganic salts and inorganic acids such as potassium dihydrogen phosphate, sodium silicate, sodium polyphosphate, calcium hydrogen phosphate, sodium phosphate and the like may be blended.In addition to the above optional components, if necessary, , Crude drugs, binders, essential oils, proteolytic enzymes, and other components. Hereinafter, specific examples of each component added to the bath agent as needed are shown.

The crude drugs include, for example, sorghum, sandalwood, valerian, scallop, squirrel, squirrel, spruce, squirrel, squirrel, carrion, squirrel, pear, peppermint, mint, shobus, matsubusa, Beak, saffron, oak, fennel, chimpanzee, ganpi, chamomile, radish, willow, camphor tree, elderberry, sokudzu, nakinata koju, yatsude, sekisho,
Artemisia, Hypericum perforatum, Yuzu, Daidai, peach, honey locust, loquat, honeysuckle, yorigusa, bodaige, horse chestnut, yarrow, hop, rosemary, cabano,
Pine, yarenzura, lantana, licorice, foxglove, marronnier and the like. These may be powders or extracted extracts.

Examples of the binder include casein, sodium carboxymethylcellulose, water-soluble gelatin,
Pectin, starch, methylcellulose, ethylcellulose, sodium alginate, polyvinyl alcohol,
Polyvinyl pyrrolidone, polyvinyl methyl ether, polyethylene glycol, karaya gum, locust bean gum, tragacanth gum, carrageenan, carbopol,
Acacia gum, agar and the like. As essential oils, for example, mint oil, jasmine oil, camphor oil,
Cypress oil, spruce oil, ryu oil, turpentine oil, cauliflower oil, bergamot oil, mandarin oil, shobu oil, pine oil, lavender oil, bay oil, clove oil, hiba oil, rose oil, eucalyptus oil, lemon oil, thyme oil , Peppermint oil, rose oil, sage oil, menthol, cineol, eugenol, citral, citronellal, borneol, linalool, geraniol, camphor, thymol, spiranthol, pinene, limonene, terpene compounds and the like. As a protease, for example,
Pepsin, trypsin, chymotrypsin, cathepsin,
Papain, promelain, ficin and bacterial yeasts, mold-derived proteases, and the like.

Specific preparation examples when the composition of the present invention is used as a bath agent are shown in the following (1) to (3). (1) Bath agent A bath agent containing 0.1 to 5% of the compound represented by the above general formula (I) in addition to the above components, and containing an inorganic salt and an inorganic acid balance, a fragrance, and a trace amount of a dye. (2) Body shampoo In addition to the above components, contains the compound represented by the above general formula (I) in an amount of 0.1 to 5%, a surfactant of 5 to 40%, a humectant of 1 to 20%, and a thickening agent. Agent 0.5 to 5%, chelating agent 0.0
Body shampoo containing 5-0.5%, purified water balance, flavor and trace amounts of pigment. (3) Body rinse In addition to the above components, the composition contains 0.1 to 5% of the compound represented by formula (I), 5 to 30% of oil, 0.5 to 5% of surfactant, and humectant. Body rinse containing 0-10%, purified water balance, trace amount of preservative, trace amount of fragrance and pigment.

Further, when the external preparation composition of the present invention is used as a cosmetic for hair, in addition to the compound represented by the above general formula (I) and each of the above optional components, for example, ethinyl estradiol, 17β-estradiol,
Estriol, estrone, cyproterone acetate, progesterone, corticosterone, hydrocortisone,
Hormones such as androstenedione and 4-androsten-3-one 17β-carboxylic acid may be blended.

Specific examples of preparation when the external preparation composition of the present invention is used as a hair cosmetic are shown below. (1) Hair tonic Compound (I) represented by the above general formula (I) is used in an amount of 0.1 to 5
%, And as an optional component, alcohols 0 to 70
%, Surfactant 0-2%, humectant 2-15%, pH adjuster 0-3%, purified water balance, trace amount of preservative, pigment 0%-
Hair tonic containing trace amounts and trace amounts of spices.

Since the external preparation composition of the present invention thus constituted contains the sulfur-containing amino acids represented by the above general formula (I), the reducing action of the sulfur-containing amino acids and the like has Water solubility and stability over time (storage stability) without inhibiting any properties such as antioxidant action, various physiologically active actions, melanin production inhibitory action, lipid peroxide decomposition accelerating action, lipid peroxide inhibitory action It will be excellent (this point will be described in detail in Examples and the like which will be described later).

[0038]

EXAMPLES Next, the present invention will be described with reference to Production Examples, Test Examples and Examples, but the present invention is not limited to the following Examples. Note that “%” in each example is “% by weight”.

Production Example 1 [Synthesis of N-D-gluconoyl-L-methionine methyl ester, N, N'-di (D-gluconoyl) -L-cystine dimethyl ester and N-D-gluconoyl-L-cysteine methyl ester According to a conventional method, any one of L-methionine methyl ester, L-cystine dimethyl ester, and L-cysteine methyl ester is added to glucono-
It is reacted with 1,5-lactone, if necessary, under a stream of argon, and purified by column chromatography to obtain ND-gluconoyl-L-methionine methyl ester and N, N'-di (D-gluconoyl) -L-, respectively. Cystine dimethyl ester and ND-gluconoyl-L-cysteine methyl ester were obtained.

(Identification of ND-gluconoyl-L-methionine methyl ester)
The identification of gluconoyl-L-methionine methyl ester was confirmed by a nuclear magnetic resonance spectrum (NMR) as shown below. (1H-NMR measurement) Measuring device: 1H-NMR measuring device (manufactured by JEOL Ltd., GX
300) (δ ppm in D2O) 1.88-2.13 (2H, br), 1.944 (3
h, s), 2.44 (2H, multi), 3.46-
3.68 (4H, br), 3.608 (3H, s),
3.921 (1H, q), 4.196 (1H, d),
4.486 (1H, q), (13C-NMR measurement) Measuring device: 13C-NMR measuring device (JEOL, G
X300) (δ ppm in D2O) 14.753 30.108, 30.199, 52.135, 53.7
80, 63.403, 71.183, 71.784, 7
2.705, 74.120, 174.496, 175.
343. Identification of N, N′-di (D-gluconoyl) -L-cystine dimethyl ester and ND-gluconoyl-L-cysteine methyl ester obtained in the above Production Examples, and the following Production Examples 2 to 10 As for the identification of each compound in, it was confirmed that satisfactory nuclear magnetic resonance spectra were obtained unless otherwise specified.

Production Example 2 [Synthesis of 2-methylcarboxy-2-gluconoylaminoethanesulfinic acid] L-cysteine methyl ester was oxidized with hydrogen peroxide in the presence of a catalytic amount of potassium iodide, and then sodium hydroxide aqueous solution was used. And the resulting L-cystine dimethyl ester was filtered off and purified by ion exchange column chromatography to obtain 2-methylcarboxy-2-aminoethanesulfinic acid. Production Example 1 under argon flow
2-methylcarboxy-2-gluconoylaminoethanesulfinic acid was obtained by the same reaction with glucono-1,5-lactone and purification method as described above.

Production Example 3 [Synthesis of 2-methylcarboxy-2-gluconoylaminoethanethiosulfonic acid] The 2-methylcarboxy-2-aminoethanesulfinic acid obtained in Production Example 2 and sulfur powder were heated under alkaline conditions. Thereafter, the resulting 2-methylcarboxy-2-aminoethanethiosulfonic acid was purified by column chromatography and purified under the same conditions as in Production Example 1 by glucono-1,5-
2-Methylcarboxy-2-gluconoylaminoethanethiosulfonic acid was obtained by a reaction with a lactone and a purification method.

Production Example 4 [ND-gluconoyl-L-methionine, N, N'-di (D-gluconoyl) -L-cystine, ND-gluconoyl-L-cysteine, 2-
Synthesis of carboxy-2-gluconoylaminoethanesulfinic acid and 2-carboxy-2-gluconoylaminoethanethiosulfonic acid] After hydrolyzing each of the compounds obtained in Production Examples 1, 2 and 3 under hydrochloric acid, Purification by column chromatography as necessary gave the desired compounds.

Production Example 5 [Synthesis of N- (2,3,4,5,6-pentahydroxyhexyl) methionine methyl ester] Reductive reaction of methionine methyl ester and D-pentaacetylglucose with sodium cyanoborohydride in methanol N- (2,3,4,5,6-
After obtaining (pentaacetylhexyl) methionine methyl ester, purification by column chromatography and methanol decomposition with a methanol solution of hydrochloric acid were performed to obtain the desired compound.

Production Example 6 [Synthesis of N- (2,3,4,5,6-pentahydroxyhexyl) cysteine methyl ester] Cystine dimethyl ester and D-pentaacetylglucose were heated in methanol and then borohydride. Reduction with sodium and purification by column chromatography gave N- (2,3,4,5,6-pentaacetylhexyl) cysteine methyl ester. This was subjected to methanolysis with a methanolic hydrochloric acid solution to obtain the desired compound.

Production Example 7 [N, N'-bis (2,3,4,4
Synthesis of 5,6-pentahydroxyhexyl) cystine dimethyl ester] The N- (2,3,4,5,6-pentaacetylhexyl) cysteine methyl ester obtained in Production Example 6 was converted to o-iodosobenzoic acid in water / methanol. Then, purification by column chromatography and methanolysis with a methanol solution of hydrochloric acid were performed to obtain the desired compound.

Production Example 8 [2-Methylcarboxy-2-
(Synthesis of (2,3,4,5,6-pentahydroxyhexylamino) ethanesulfinic acid) Using N- (2,3,4,5,6-pentahydroxyhexyl) cysteine methyl ester obtained in Production Example 7 as a catalyst After oxidizing with hydrogen peroxide in the presence of potassium iodide, the mixture is treated with an aqueous sodium hydroxide solution and the resulting N, N'-bis (2,3,4,5,6-pentahydroxyhexyl) cystine dimethyl ester is filtered. After separation, the mixture was purified by ion exchange column chromatography to obtain 2-methylcarboxy-2- (2,3,4,5,6-pentahydroxyhexylamino) ethanesulfinic acid.

Production Example 9 [2-Methylcarboxy-2-
(Synthesis of (2,3,4,5,6-pentahydroxyhexylamino) ethanethiosulfonic acid) 2-methylcarboxy-2- (2,3,2) obtained in Production Example 8
After heating 4,5,6-pentahydroxyhexylamino) ethanesulfinic acid and sulfur powder under alkaline conditions,
The resulting 2-methylcarboxy-2- (2,3,4,5,
The crude product of 6-pentahydroxyhexylamino) ethanethiosulfonic acid was purified by column chromatography to obtain the target compound.

Production Example 10 [N- (2,3,4,5,6-
Pentahydroxyhexyl) methionine, N, N'-bis (2,3,4,5,6-pentahydroxyhexyl)
Cystine, N- (2,3,4,5,6-pentahydroxyhexyl) cysteine, 2-carboxy-2- (2
3,4,5,6-pentahydroxyhexylamino) ethanesulfinic acid and 2-carboxy-2- (2,3,
Synthesis of 4,5,6-pentahydroxyhexylamino) ethanethiosulfonic acid] After hydrolyzing each compound obtained in Production Examples 5, 6, 7, 8, and 9 under hydrochloric acid, column chromatography is performed if necessary. Purification by chromatography gave the desired compounds.

[Test Example 1 (Evaluation of Hydroxy Radical Scavenging Ability)] Biochim. Acta. 4
7 (1988), 10/11, S252-S255, the hydroxyl radical scavenging ability of each sulfur-containing amino acid obtained in Production Examples 1 to 10 was evaluated. That is, 50 μM ferrous sulfate and 100 μM hydrogen peroxide were added in the presence of 1 mM DMPO and 150 mM NaCl for 2 hours.
The resulting DMPO-O was mixed at 5 ° C., pH 6.5 and the resulting DMPO-O
H spin adduct is ESR (RE-1X manufactured by JEOL Ltd.)
Was determined. DMP when the substance to be evaluated does not coexist
When the signal intensity of O-OH is 1, this is 0.5
The concentration (50% inhibitory concentration) at which the hydroxyl radical was scavenged was used as an index of the hydroxyl radical scavenging ability. The results are shown in Table 1 below.

[0051]

[Table 1]

From the results shown in Table 1 above, the above Production Examples 1 to 10
Even if the amino group of each sulfur-containing amino acids obtained in the above is modified with a polyhydroxyalkyl group derived from a saccharide,
It was revealed that the antioxidant ability was maintained.

Examples 1 to 20 and Comparative Examples 1 to 5 (Preparation of Beauty Essence) Formulations shown in Table 2 below were prepared by a conventional method. The obtained 1 to 20 and Comparative Examples 1 to 5 were evaluated for stability by the following evaluation method. The results are shown in Table 2 below. The composition of the fragrance used in Table 2 is shown in Table 3 below.
Shown in [Evaluation Method of Stability] The storage stability of the preparation was evaluated in a constant temperature bath at 40 ° C. for 1 month and 3 months, according to the following evaluation criteria. Evaluation criteria: ○: no change in state such as separation and off-flavor at all, and good ×: change in state such as separation and off-odor is recognized

[0053]

[Table 2]

[0054]

[Table 3]

As can be seen from the results shown in Table 2, in Comparative Examples 1 to 5, which are liquid beauty essences, after one month, an unpleasant odor considered to be caused by the decomposition of cysteine, methionine and the like was generated.
On the other hand, in Examples 1 to 20, even after 3 months, there was no sample in which an offensive odor or separation was recognized, and it was revealed that the storage stability of the preparation was clearly improved. .

Examples 21 and 22 and Comparative Examples 6 and 7 (Preparation of the first permanent wave agent) The compositions shown in Table 4 below were prepared by a conventional method. Example 21 and 2 obtained
2 and Comparative Examples 6 and 7 were evaluated for odor using a specialized paneler according to the following evaluation method. The results are shown in Table 4 below. The composition of the fragrance used in Table 4 was as shown in Table 3 above. [Odor evaluation method] The evaluation was made based on the following evaluation criteria, out of 5 points, and evaluated by the average value of evaluations by 10 panelists. Evaluation criteria: 1: Strong odor / irritation odor 2: Clear odor / irritation odor 3: Slight odor / irritation odor 4: No odor / irritation odor 5: Preferable odor

[0057]

[Table 4]

As can be seen from the results in Table 4 above, in Comparative Examples 6 and 7, the foul odor peculiar to the first permanent wave agent was obtained.
Although irritating odors were recognized, it was found in Examples 21 and 22 that these odors were significantly improved.

[Examples 23 to 35] Hair lotions, lotions, emulsions, packs, bath preparations (granules), bath preparations (powder forms) which are specific examples of the external preparation composition of the present invention are described below. ), Bath preparations (tablets), bath preparations (foamed), bath preparations (liquid), body shampoos, body rinses, hair tonics, and patches. In addition, for these hair lotions, lotions, emulsions, packs, bath preparations, body shampoos, body rinses, hair tonics, and patches, the stability after 1 month and 3 months was evaluated in the same manner as in Example 1. However, it was found that there was no change in the state such as separation and off-flavor at all, and it was good. Example 2
Table 3 shows the composition of the fragrance used in Examples 3 to 35.
The following was used.

Example 23 (Preparation of hair lotion) A hair lotion having the following composition was prepared by a conventional method. N, N'-di (D-gluconoyl) -L-cystine dimethyl ester 3.0% ethanol 28.0% POE hydrogenated castor oil 0.5% 1,3-butylene glycol 7.0% Fragrance trace amount Purified water Balance 100% in total

Example 24 (Preparation of lotion) A lotion having the following composition was prepared by a conventional method. 2-Methylcarboxy-2-gluconoylaminoethanesulfinic acid 1.0% Glycerin 4.0% Ethanol 10.0% Xanthan gum 0.3% Fragrance trace amount Purified water Balance Total 100%

Example 25 (Preparation of emulsion) An emulsion having the following composition was prepared by a conventional method. 2-Methylcarboxy-2-gluconoylaminoethanethiosulfonic acid 1.0% Stearic acid 1.0% Cetanol 2.0% Vaseline 2.5% Squalane 4.0% L-Arginine 1.0% Lipophilic mono Glycerin stearate 1.0% Glycerin 2.0% Potassium hydroxide 0.1% Fragrance trace amount of methyl paraben 0.1% Butyl paraben 0.05% Purified water Balance Total 100%

Example 26 (Preparation of Packing Agent) The following formulations A and B were mixed and uniformly heated and mixed at 70 ° C. Formulation C was added with further cooling to prepare a pack. A: Ethanol phase part Ethanol 10.0% Polyvinyl alcohol 15.0% Propylene glycol 3.0% Methyl paraben 0.1% Butyl paraben 0.05% Glycyrrhizic acid 0.1% B: Water phase part ND-gluconoyl- L-Methionine methyl ester 1.0% Sodium carboxymethylcellulose 5.0% POE (15) oleyl ether 1.0% Purified water Balance C: Suitable amount of perfume 100%

Example 27 [Preparation of bath agent (granular)] A bath agent (granular) having the following composition was prepared by a conventional method. Potassium bicarbonate Balance Sodium sulfate 30.0% N-D-gluconoyl-L-cysteine 1.0% Magnesium oxide 2.0% Sodium carboxymethyl cellulose 1.0% Chamomile 0.5% Vitamin E 0.5% Fragrance 1. 0% Dye 0.1% Total 100%

Example 28 Preparation of Bath Agent (Powder) A bath agent (powder) having the following composition was prepared by a conventional method. Sodium carbonate balance Sodium bicarbonate 32.1% N- (2,3,4,5,6-pentahydroxyhexyl) cysteine 1.0% Pepsin enzyme (200U) 1.0% Sodium citrate 3.0% Limonene 0 0.5% Lavender oil 0.3% Fragrance 1.0% Pigment 0.1% Total 100%

Example 29 [Preparation of bath agent (tablet)] A bath agent (tablet) having the following composition was prepared by a conventional method: sodium carbonate balance sodium hydrogen carbonate 25.4% succinic acid 40.0% N- (2,3,4,5,6-pentahydroxyhexyl) methionine 1.0% Alame powder 0.5% Kajime powder 0.5% Aloe powder 0.5% Fragrance 1.0% Pigment 0.1% Total 100%

Example 30 Preparation of Bath Agent (Foam Form) A bath agent (foam form) having the following composition was prepared by a conventional method. Sodium carbonate Balance Sodium sulfate 8.0% Sodium bicarbonate 30.0% ND-gluconoyl-L-methionine 1.0% Citric acid 20.0% Tartaric acid 10.0% Succinic acid 10.0% Flavor 1.5 % Dye 0.1% Total 100%

Example 31 Preparation of Bath Agent (Liquid) A bath agent (liquid) having the following composition was prepared by a conventional method. Propylene glycol Balance Ethanol 20.0% Sodium sulfate 5.0% N- (2,3,4,5,6-pentahydroxyhexyl) methionine methyl ester 1.0% Lanolin 0.5% Avocado oil 0.5% Fragrance 21.0% Dye 0.1% Total 100%

Example 32 (Preparation of body shampoo) A body shampoo having the following composition was prepared by a conventional method. Potassium coconut fatty acid 5.0% Potassium oleate 20.0% Coconut fatty acid diethanolamide 3.0% Glycerin 10.0% Sodium sulfate 2.0% EDTA 0.1% 2-Carboxy-2-gluconoylaminoethanesulfinic acid 1.0% Perfume Appropriate amount Dye Appropriate amount Preservative Appropriate amount Purified water Balance Total 100%

Example 33 (Preparation of body rinse) A body rinse having the following composition was prepared by a conventional method. Liquid paraffin 10.0% Isopropyl palmitate 3.0% Methylpolysiloxane 3.0% Potassium cocoate 5.0% Potassium oleate 20.0% Glycerin monostearate 1.5% POE Glycerin stearate 1.5% Glycerin 5.0% 2-Carboxy-2- (2,3,4,5,6-pentahydroxyhexylamino) ethanesulfinic acid 1.0% Fragrance Appropriate amount Pigment Appropriate preservative Appropriate amount Purified water Balance Total 100%

Example 34 (Preparation of Hair Tonic) A hair tonic having the following composition was prepared by a conventional method. 2-Methylcarboxy-2- (2,3,4,5,6-pentahydroxyhexylamino) ethanesulfinic acid 1.0% Glycerin 4.0% Ethanol 10.0% Xanthan gum 0.3% Fragrance Trace amount Purified water Balance 100% in total

Example 35 (Preparation of Patch) After mixing the following components, they were thoroughly mixed until a paste was formed, and the resulting patch composition was applied on a nonwoven fabric at 150 g / m ^2.
Was applied uniformly to give a polyethylene film to prepare a patch. Polyacrylic acid 4.0% Sodium polyacrylate 1.5% Sodium carboxymethylcellulose 4.0% Glycerin 15.0% Sorbitol 10.0% Dihydroxyaluminum amino acetate 0.1% Synthetic hydrotalcite 0.05% Kaolin 4 1.0% Polysorbate 80 1.0% 1,3-butylene glycol 3.0% 2-carboxy-2-gluconoylaminoethanethiosulfonic acid 5.0% Silicone oil 4.0% Purified water 51.35% Total 100%

[0073]

According to the present invention, stabilization can be realized without impairing the properties of sulfur-containing amino acids or derivatives thereof and without impairing the water solubility of sulfur-containing amino acids or derivatives thereof. Provided are a stabilized sulfur-containing amino acid or a derivative thereof, which is extremely easily incorporated into a composition, and an external preparation composition containing the same.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07C 381/02 C07C 381/02 (72) Inventor Masako Ishii 1-3-7, Honjo, Sumida-ku, Tokyo 4C083 AA112 AA122 AB082 AB212 AB312 AB352 AB442 AC012 AC022 AC032 AC072 AC102 AC122 AC132 AC182 AC242 AC302 AC352 AC422 AC432 AC532 AC542 AC581 AC582 AC642 AC772 AC792 AD092 AD112 AD152 AD272 AD352 AD472 AD512 CC662 CC01 CC23 CC25 CC32 CC37 DD08 DD12 DD15 DD16 DD17 DD23 DD31 EE01 EE22 FF05 4C206 AA01 FA44 MA83 NA03 ZA89 4H006 AA01 AA03 AB12 BV34 TA04 TB55 TC34

Claims (2)

[Claims] 1. A stabilized sulfur-containing amino acid or a derivative thereof, comprising at least one compound represented by the following general formula (I). Embedded image 2. An external preparation composition comprising the sulfur-containing amino acids according to claim 1 or a derivative thereof.