JPH1053517A - Aging resistant and collagen crosslinking preventive skin lotion - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject lotion exhibiting the effects for suppressing the crosslinking of a collagen and a cellular disorder by formulating a specific N-acetyl cysteine as an active ingredient. SOLUTION: This aging resistant and collagen crosslinking preventing dermal agent for external use is obtained by blending N-acetyl cysteine expressed by the formula as an active ingredient. The compound of the formula is a material obtained by the condensation of acetyl group with an amino group of cysteine with dehydration. The blending amount of the N-acetyl cysteine of the formula in the above agent is approximately 0.0005-0.5wt.%, preferably 0.001-0.1wt.% based on the total amount of the dermal agent for external use. The dermal agent for external use can maintain the elasticity of the skin and prevent the skin from forming a wrinkle or a slack.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention belongs to the technical field of skin external preparations, and more specifically, an anti-aging skin external preparation for preventing skin aging and a skin cross-linking agent which mainly inhibits collagen crosslinking in the dermis. The present invention relates to a skin external preparation for preventing collagen crosslinking, which maintains elasticity and prevents wrinkles and sagging.

[0002]

2. Description of the Related Art It is known that the skin becomes thinner and its metabolism decreases with aging. As a cause of such skin aging, aging is an important factor from a macro perspective, and furthermore, drying, oxidation by active oxygen, etc.
The effects of sunlight due to ultraviolet rays are also considered to be direct factors related to skin aging. Conventionally, various measures have been taken to prevent such aging of the skin.

[0003] For example, a skin external preparation containing various moisturizers to prevent skin aging due to drying, a skin external preparation containing an antioxidant such as vitamin E to prevent skin aging due to oxidation, Skin external preparations and the like containing an ultraviolet absorber for preventing skin aging due to ultraviolet rays have already been provided. However, these conventional means for preventing skin aging are all means focusing on factors that are consequently associated with skin aging, and are unable to leave the area of "coping therapy" and obtain a sufficient effect of preventing skin aging. It cannot be denied that it cannot be done. Therefore, there is a current need to establish a "radical therapy" means to stop the more direct phenomenon that progresses skin aging.

[0004]

As a more direct phenomenon that progresses skin aging, an increase in collagen cross-linking (hereinafter referred to as collagen cross-linking) mainly in the dermis is known. It is also known that cells are reduced or deformed (Cutaneous AgingEdited by
Albert M. Kligman and Yoshio Takasu University of
Tokyo Pres, 263-274, 1988; Sugiyama T., Fujimoto D., A
rai C. and Hasegawa M., Biomed Res 8 , 349-351,198
7).

That is, the various skin aging factors described above,
In particular, with exposure to ultraviolet rays (especially, long-wavelength ultraviolet rays (UV-A) which easily reach the dermis) (for collagen crosslinking by exposure to ultraviolet rays, see “Fujimori E., FEBS Lett 235 ”) .
( 1-2), 98-102, 1988 ", and describes that cells are damaged by exposure to ultraviolet light.
npure and RMTyrrel, Photochem PhotoBiol 23,171-17
7,1976 "). The proliferation activity of fibroblasts, which are the main cells in the dermis, and the synthesis and synthesis of collagen, etc.
The decomposition function is reduced, and the turnover speed of the collagen and the like is also reduced. As a result, collagen and the like are subjected to various modifications and denaturation, and it is presumed that the collagen crosslinks in the skin increase. As the collagen crosslinking increases, the skin becomes less elastic, wrinkles and sagging increase, and the skin ages. The present invention has established a "radical therapy" means to halt the progress of this collagen crosslinking and cell damage, including the prevention of skin aging,
It is an object of the present invention to provide an anti-aging skin external preparation and a collagen cross-linking prevention skin external preparation that meet the needs of various industries.

[0006]

Means for Solving the Problems The present inventor has made intensive studies in view of the above problems. As a result, a specific N-acetylcysteine has an effect of suppressing collagen crosslinking and an effect of suppressing cell damage, and provides an anti-aging skin external preparation and a collagen cross-linking prevention skin external preparation containing this compound as an active ingredient. As a result, it has been found that this problem can be solved.

That is, in the present application, the present inventors have prepared an anti-aging skin external preparation containing N-acetylcysteine represented by the following formula (I) HOOC-CHNH (OCCH ₃ ) CH ₂ SH (I) as an active ingredient, A skin external preparation for preventing collagen cross-linking, comprising N-acetylcysteine (I) as an active ingredient.

[0008]

Embodiments of the present invention will be described below. The N-acetylcysteine (I) compounded in the anti-aging skin external preparation of the present invention and the skin external preparation for preventing collagen cross-linking of the present invention is a substance in which an acetyl group is dehydrated and condensed to an amino group of cysteine. ". This N-acetylcysteine (I)
It is a substance discovered from mycobacteria which is a genus of actinomycetes in the 960's, and is known to have radioactive damage protection and cytotoxicity alleviating effects.

Therefore, N-acetylcysteine (I)
Can be extracted from the above actinomycetes by a generally known method, and can also be chemically synthesized by a generally known method. Further, in the present invention, commercially available N-acetylcysteine (I) may be used in addition to those obtained by separate chemical synthesis or the like by a generally known method as described above.
Can be widely used. N-acetylcysteine (I) which can be incorporated into the anti-aging skin external preparation of the present invention and the skin external preparation for preventing collagen cross-linking of the present invention includes, for example, Wako Pure Chemical Industries, Ltd., Tokyo Chemical Industry Co., Ltd., Sigma (Sigma), It is sold by Sasaki Chemical Co., Iwase Cosfa, Ajinomoto Co., and others.

The amount of N-acetylcysteine (I) in the anti-aging skin external preparation of the present invention and the skin external preparation of the present invention for preventing collagen cross-linking is 0.000 of the total skin external preparation.
It is not less than 05% by weight and not more than 0.5% by weight, preferably not less than 0.001% by weight and not more than 0.1% by weight. If the amount is less than 0.0005% by weight of the whole skin external preparation, a sufficient anti-skin aging effect or collagen cross-linking preventing effect is not exhibited, and even if the amount is more than 0.5% by weight, the amount increases. In addition, no anti-skin aging effect or collagen cross-linking preventing effect can be expected.

[0011] A skin external preparation for preventing collagen cross-linking thus containing N-acetylcysteine (I) is as follows:
By preventing collagen cross-linking, the elasticity of the skin can be maintained, wrinkles and sagging can be prevented, and beautiful skin can be maintained.

Further, the anti-aging skin external preparation of the present invention suppresses damage to skin cells and suppresses collagen crosslinking, thereby aging, drying, oxidation by active oxygen and the like, and the influence of ultraviolet rays of sunlight. Can suppress the progress of skin aging by skin cells and skin extracellular matrix in general

As described above, the anti-aging skin external preparation of the present invention and the skin external preparation of the present invention for preventing collagen cross-linking, which contain N-acetylcysteine (I) as an active ingredient, can sufficiently exhibit the expected effects as described above. It is possible. However, by the addition of other medicinal ingredients as needed, for the purpose of imparting effects that skin external preparations such as cosmetics will generally exhibit,
Mixing the other medicinal ingredients into the anti-aging skin external preparation of the present invention and the collagen cross-linking prevention skin external preparation of the present invention,
It is possible within the range where the intended effect of the present invention is not impaired by the compounding.

For example, an ultraviolet absorber can be incorporated into the anti-aging skin external preparation of the present invention and the collagen cross-linking preventing skin external preparation of the present invention for the purpose of removing the adverse effects of ultraviolet rays from sunlight. For example, methyl anthranilate, anthranilic acid UV absorbers such as homomenthyl -N- acetyl anthranilate; 2, 4-dihydroxybenzophenone, 2, 2 ^'- dihydroxy-4-methoxybenzophenone, 2, 2' - dihydroxy - Four,
4'-dimethoxybenzophenone, 2,2 ', 4,4'-
Tetrahydroxybenzophenone, 2-hydroxy-4
-Methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2-hydroxy-
4-methoxybenzophenone-5-sulfonate, 4-
Phenylbenzophenone, 2-ethylhexyl-4'-
Phenyl-benzophenone-2-carboxylate, 2
-Hydroxy-4-n-octoxybenzophenone, 4
A benzophenone ultraviolet absorber such as -hydroxy-3-carboxybenzophenone; 2,2'-hydroxy-5
- methylphenyl benzotriazole, 2- (2 ^'- hydroxy-5'-tert - octylphenyl) benzotriazole, 2- ^(2' - hydroxy-5'-methylphenyl) benzotriazole ultraviolet absorbers such as benzotriazole; Dianisoylmethane, 4-methoxy-4 ^'
-Long wavelength ultraviolet (UV-A) absorbers such as tert -butyldibenzoylmethane (Parsol A) can be blended.

Further, para-aminobenzoic acid (hereinafter referred to as PAB)
A), PABA monoglycerin ester, N, N
-Dipropoxy PABA ethyl ester, N, N-diethoxy PABA ethyl ester, N, N-dimethyl PA
Para-aminobenzoic acid ultraviolet absorbers such as BA ethyl ester, N, N-dimethyl PABA butyl ester, N, N-dimethyl PABA amyl ester; dipropylene glycol salicylate, ethylene glycol salicylate, myristyl salicylate, methyl salicylate, amyl salicylate, menthyl Salicylic acid ultraviolet absorbers such as 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-2,4-diisopropylcinnamate, methyl-2,4-diisopropylcinnamate, propyl-p-methoxy Nameto, isopropyl -p
-Methoxycinnamate, isoamyl-p-methoxycinnamate, octyl-p-methoxycinnamate (2
-Ethylhexyl-p-methoxycinnamate), 2-
Ethoxyethyl-p-methoxycinnamate, cyclohexyl-p-methoxycinnamate, ethyl-α-cyano-β-phenylcinnamate, 2-ethylhexyl-
α-cyano-β-phenylcinnamate, glyceryl mono-2-ethylhexanoyl-diparamethoxycinnamate, octyl methoxycinnamate, 3,4-, 5-trimethoxycinnamate-3-methyl-4- [ Cinnamic acid-based ultraviolet absorbers such as methylbis (trimethylsiloxy) silyl] butyl and p-dimethoxycinnamic acid monoethyl ester;
3- (4'-methylbenzylidene) -d, 1-camphor, 3-benzylidene-d, 1-camphor, 5- (3,
Camphor derivatives such as 3-dimethyl-2-norbornylidene) -3-penten-2-one; medium wavelength ultraviolet light (UV-B) such as urocanic acid, urocanic acid ethyl ester, 2-phenyl-5-methylbenzoxazole, and dibenzarazine An absorbent can be included.

Further, as an ultraviolet blocking agent, titanium oxide (TiO ₂ ), talc (MgSiO ₂ ), carmine (F
eO ₂ ), bentonite, kaolin, zinc oxide (Zn)
O) and the like.

[0017] For example, polyethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol,
Hexylene glycol, xylitol, sorbitol,
Maltitol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, caronic acid, atelocollagen, cholesteryl-12-hydroxystearate, sodium lactate, bile salts, dl-pyrrolidone carboxylate, short-chain soluble collagen, diglycerin (EO) PO A moisturizing agent such as an adduct, a primrose extract, an extract of Achillea millefolium, and a melilot extract can be incorporated into the anti-aging skin external preparation of the present invention and the skin external preparation of the present invention for preventing collagen crosslinking.

Providing a whitening effect is useful for the purpose of, for example, reducing the adverse effect of ultraviolet rays on the skin. In this case, it is possible to mix a whitening agent such as a placenta extract, glutathione, or Saxifraga extract in the anti-aging skin external preparation of the present invention and the collagen cross-linking preventing skin external preparation of the present invention.

Providing an anti-inflammatory effect is useful for the purpose of mitigating adverse effects on the skin due to ultraviolet rays, as described above. In this case, an anti-inflammatory agent such as a glycyrrhizic acid derivative, a glycyrrhetinic acid derivative, a salicylic acid derivative, hinokitiol, zinc oxide, and allantoin can be blended into the anti-aging skin external preparation of the present invention and the collagen cross-linking preventing skin external preparation of the present invention. It is.

Similarly, activators such as royal jelly, photosensitizer No. 301, cholesterol derivatives, calf blood extract and the like; valenylamide nonylate for the purpose of alleviating the adverse effects of ultraviolet rays on the skin and further suppressing skin aging. , Nicotinic acid benzyl ester, nicotinic acid β-butoxyethyl ester, capsaicin, gingerone, cantaristin tincture, ittamol, caffeine, tannic acid, α-borneol, nicotinic acid tocopherol, inositol hexanicotinate, cyclandate, cinnarizine, tolazoline A blood circulation promoter such as acetylcholine, verapamil, cepharanthin, γ-oryzanol, etc .; an antiseborrheic agent such as sulfur, thiantol, etc. may be blended into the anti-aging skin external preparation of the present invention and the skin external preparation of the present invention for preventing collagen crosslinking. It is possible.

In addition, for various purposes, oat extract components, spinach extract components, sicon extract components, peonies extract components, assembly extract components, birch extract components, sage extract components, loquat extract components, carrot extract components, aloe extract components, Mallow extract, iris extract, grape extract, yokuinin extract, loofah extract, lily extract, saffron extract, nematode extract, ginger extract, hypericum extract, ononis extract, rosemary extract, Garlic extract,
It is possible to mix a plant extract such as a pepper extract component, a cockroach and a corn in the anti-aging skin external preparation of the present invention and the collagen cross-linking preventing skin external preparation of the present invention.

Further, vitamin A such as vitamin A oil, retinol, retinol acetate and the like; riboflavin, in order to further impart a unique effect of each vitamin, for example, an effect of inhibiting skin aging to the collagen crosslinking inhibitor of the present invention. , riboflavin butyrate, vitamin B ₂ such as flavin adenine nucleotide; pyridoxine hydrochloride, vitamin B ₆ such as pyridoxine dioctanoate; L-ascorbic acid, L- ascorbic acid dipalmitate esters,
L-ascorbic acid-2-sodium sulfate, L-ascorbic acid phosphate, DL-α-tocopherol-
Vitamin Cs such as dipotassium L-ascorbic acid diester phosphate; pantothenic acids such as calcium pantothenate, D-pantothenyl alcohol, pantothenyl ethyl ether and acetyl pantothenyl ethyl ether; vitamin D such as ergocalciferol and cholecalciferol Nicotinic acids such as nicotinic acid, nicotinamide, benzyl nicotinate; α-tocopherol, tocopherol acetate, DL-α-tocopherol nicotinate;
Vitamin Es such as DL-α-tocopherol succinate;
Other vitamins such as vitamin P and biotin can be blended in the anti-aging skin external preparation of the present invention and the collagen cross-linking preventing skin external preparation of the present invention.

The above-mentioned medicinal components are not limited to other medicinal components which can be incorporated into the anti-aging skin external preparation of the present invention and the collagen external skin preventing agent of the present invention. In addition, the medicinal properties corresponding to the other medicinal ingredients listed above,
It is not limited to the above. For example, vitamin Cs can be used as a whitening component and also as an antioxidant aid. Furthermore, in addition to the above-mentioned other medicinal ingredients being independently compounded in the collagen crosslinking inhibitor of the present invention, two or more kinds of the above-mentioned medicinal ingredients may be appropriately combined and compounded according to the purpose. is there.

The anti-aging skin external preparation of the present invention and the skin external preparation of the present invention for preventing collagen cross-linking can be widely applied to cosmetics, pharmaceuticals, quasi-drugs and the like applied to the outer skin, and their dosage forms Also aqueous solution type, solubilizing type, emulsifying type, powder type, oil liquid type, gel type, ointment type, aerosol type, water-oil 2
A wide range of dosage forms can be employed, such as a layer system, a water-oil-powder three-layer system, and the like.
That is, basic cosmetics can be widely applied to the above-mentioned various dosage forms in the form of facial cleanser, lotion, milky lotion, cream, gel, essence (cosmetic), pack mask and the like. In addition, makeup cosmetics can be widely applied to forms such as foundations. Furthermore, if it is a medicine or a quasi-drug, it can be widely applied to various ointments and the like. The form and form of the anti-aging skin external preparation of the present invention and the skin external preparation of the present invention for preventing collagen crosslinking are not limited to these dosage forms and forms.

In the collagen crosslinking inhibitor of the present invention,
Depending on the desired dosage form and form, generally known base components can be widely blended within the range where the intended effects of the present invention are not impaired by their blending. That is, avocado oil, camellia oil, evening primrose oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, sasanqua oil, castor oil, linseed oil, saury oil Flower oil, cottonseed oil, eno oil, soybean oil, peanut oil, teaseed oil, kaya oil, rice bran oil, sinagiri oil, Japanese kiri oil, jojoba oil, germ oil,
Liquid fats and oils such as triglycerin, glyceryl trioctanoate, and glycerin triisopalmitate; cocoa butter, coconut oil, horse fat, hydrogenated coconut oil, palm oil, tallow, sheep tallow, hardened tallow, palm kernel oil, lard, beef bone Solid oils such as fats, mocro kernel oil, hardened oil, beef tallow, mokuro, hardened castor oil; beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, ibota wax, whale wax, montan wax, nukaro, lanolin, kapok wax, lanolin acetate, Liquid lanolin, sugarcane wax, isopropyl lanolin fatty acid, hexyl laurate, reduced lanolin, jojoba wax, hard lanolin, shellac wax, POE lanolin alcohol ether, POE lanolin alcohol acetate, POE cholesterol ether, lanolin fatty acid polyethylene glycol It waxes such as POE hydrogenated lanolin alcohol ether;

Liquid paraffin, ozokerite, squalene, pristane, paraffin, ceresin, squalene,
Hydrocarbon oils such as petrolatum, oils such as microcrystalline wax; lauric acid, myristic acid, palmitic acid, stearic acid, behenic (beheninic) acid, oleic acid, 12-hydroxystearic acid, undecylenic acid,
Higher fatty acids such as tollic acid, isostearic acid, linoleic acid, linoleic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA); lauryl alcohol;
Straight-chain alcohols such as cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, and cetostearyl alcohol, monostearyl glycerin ether (bacyl alcohol), 2-decyltetradecinol, lanolin alcohol, cholesterol, phytosterol, hexyldecanol, Higher alcohols such as branched alcohols such as isostearyl alcohol and octyldodecanol;

Isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate , Isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexylate, fatty acid ester of dipentaerythritol, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate, diisostearyl malate Glycerin di-2-heptylundecanoate, tri-
Trimethylolpropane 2-ethylhexylate, trimethylolpropane triisostearate, tetra-2-
Pentane erythritol ethylhexylate, tree 2-
Glycerin ethylhexylate, trimethylolpropane triisostearate, cetyl-2-ethylhexanoate, 2-ethylhexyl palmitate, glycerin trimyristate, glyceride tri-2-heptylundecanoate, methyl ester of castor oil fatty acid, oleic acid 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 sebacate
-Ethylhexyl, 2-hexyldecyl myristate,
2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebacate, 2-succinic acid
Synthetic ester oils such as ethylhexyl, ethyl acetate, butyl acetate, amyl acetate, and triethyl citrate; linear polysiloxanes such as dimethylpolysiloxane, methylphenylpolysiloxane, and methylhydrogenpolysiloxane, decamethylpolysiloxane, dodecamethylpolysiloxane , Polycyclic silicones such as tetramethyltetrahydrogenpolysiloxane, silicones forming a three-dimensional network structure, silicones such as silicone rubber;

Soap base, sodium laurate,
Fatty acid soaps such as sodium palmitate, higher alkyl sulfates such as sodium lauryl sulfate and lauryl sulfate K, alkyl ether sulfates such as POE lauryl sulfate triethanolamine and sodium POE lauryl sulfate, and N-acyls such as sodium lauroyl sarcosine Higher fatty acid amide sulfonates such as sarcosine acid, sodium N-myristoyl-N-methyltaurine, sodium coconut fatty acid methyl tauride, sodium lauryl methyl tauride, phosphorus such as sodium POE oleyl ether phosphate, POE stearyl ether phosphoric acid Acid ester salts, sodium di-2-ethylhexylsulfosuccinate, sodium monolauroylmonoethanolamide polyoxyethylenesulfosuccinate,
Sulfosuccinates such as sodium lauryl polypropylene glycol sulfosuccinate, sodium linear dodecylbenzenesulfonate, triethanolamine linear dodecylbenzenesulfonate, alkylbenzene sulfonates such as linear dodecylbenzenesulfonate, monosodium N-lauroylglutamate, N-stearoyl N-acyl glutamates such as disodium glutamate and monosodium N-myristoyl-L-glutamate; higher fatty acid ester sulfates such as hydrogenated coconut oil fatty acid sodium glycerin sulfate; sulfated oils such as funnel oil; POE alkyl ether carboxylic acid , POE alkyl allyl ether carboxylate, α-olefin sulfonate, higher fatty acid ester sulfonate, secondary alcohol sulfate , Higher fatty acid alkylol amide sulfate, lauroyl monoethanolamide sodium succinate, N- palmitoyl aspartate ditriethanolamine, anionic surfactants such as casein sodium;

Stearyltrimethylammonium chloride,
Alkyltrimethylammonium salts such as lauryltrimethylammonium chloride, distearyldimethylammonium dialkyldialkyldimethylammonium chloride,
Poly (N, N'-dimethyl-3,5-methylenepiperidinium chloride), alkylpyridinium salts such as cetylpyridinium chloride, alkyl quaternary ammonium salts, alkyldimethylbenzylammonium salts, alkylisoquinolinium salts, and dialkylmorpholine Ammonium salt, POE alkylamine, alkylamine salt, polyamine fatty acid derivative, amyl alcohol fatty acid derivative, benzalkonium chloride,
Cationic surfactants such as benzethonium chloride; 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl-2-imitazolinium hydroxide-1-carboxyethyloxy Betaine interfaces such as imidazoline amphoteric surfactants such as disodium salt, 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetate betaine, alkyl betaine, amido betaine, sulfobetaine, etc. Amphoteric surfactants such as surfactants;

Sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, tetra- Sorbitan fatty acid esters such as 2-ethylhexyl diglycerol sorbitan and the like, mono-cottonseed oil fatty acid glycerin, glycerin monoerucate, glyceryl sesquioleate, glyceryl monostearate, α, α'-glycerin pyroglutamate oleate, glycerin monostearate malate Polyglycerin fatty acids such as propylene glycol fatty acid esters such as propylene glycol monostearate, hydrogenated castor oil derivatives Glycerin alkyl ethers, lipophilic nonionic surfactants such as polyoxyethylene-methylpolysiloxane copolymer;

POE sorbitan monooleate, POE
-POE sorbitan fatty acid esters such as sorbitan monostearate, POE-sorbitan monooleate, POE-sorbitan tetraoleate, POE-sorbit monolaurate, POE-sorbit monooleate, POE-sorbit pentaoleate, POE-sorbit POE sorbitol fatty acid esters such as monostearate, POE-glycerin monostearate, P
POE glycerin fatty acid esters such as OE-glycerin monoisostearate, POE-glycerin triisostearate, POE fatty acid esters such as POE monooleate, POE distearate, POE monodiolate, ethylene glycol cysteate, POE lauryl ether, POE oleyl 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
POE alkyl phenyl ethers such as E dinonyl phenyl ether; pluronic type such as bruronic;
POE / POP cetyl ether, POE / POP2-decyltetradecyl ether, POE / POP monobutyl ether, POE / POP hydrogenated lanolin, POE / PO
POE / POP alkyl ethers such as P-glycerin ether, and tetra-POE / tetra-POP such as Tetronic
Ethylenediamine condensates, POE castor oil, POE hardened castor oil, POE hardened castor oil monoisostearate, POE hardened castor oil triisostearate, POE
PO such as hydrogenated castor oil monopyroglutamic acid monoisostearate diester, POE hydrogenated castor oil maleic acid, etc.
E Castor oil-hardened castor oil derivatives, POE beeswax lanolin derivatives such as POE sorbitol beeswax, alkanolamides such as coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, POE propylene glycol fatty acid ester, P
Hydrophilic nonionic surfactants such as OEalkylamine, POE fatty acid amide, sucrose fatty acid ester, POE nonylphenylformaldehyde condensate, alkylethoxydimethylamine oxide, and trioleyl phosphoric acid;

Preservatives such as methylparaben, ethylparaben, and butylparaben; sequestering agents such as sodium edetate; arabia gum, tragacanth gum, galactan, guar gum, carob gum, caraya gum, carrageenan, pectin, agar, quince seed (quinmello), Plant-based polymers such as alge colloid (cassow extract), starch (rice, corn, potato, wheat), glycyrrhizic acid, microbial polymers such as xanthan gum, dextran, succinoglucan, burlan, collagen, casein, albumin, gelatin, etc. Natural water-soluble polymers such as animal polymers; starch polymers such as carboxymethyl starch and methylhydroxypropyl starch; methylcellulose; nitrocellulose;
Cellulose polymers such as ethylcellulose, methylhydroxypropylcellulose, hydroxyethylcellulose, sodium cellulose sulfate, hydroxypropylcellulose, sodium carboxymethylcellulose (CMC), crystalline cellulose and cellulose powder; alginic acid polymers such as sodium alginate and propylene glycol alginate Semi-synthetic water-soluble polymers such as polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, carboxyvinyl polymers (such as Carbopol), vinyl polymers such as alkyl-modified carboxyvinyl polymers, polyethylene glycol 2000,
Polyoxyethylene polymers such as 4000 and 6000,
Synthetic water-soluble polymers such as polyoxyethylene polyoxypropylene copolymer copolymer polymers, sodium polyacrylate, polyethyl acrylate, polyacrylamide and other acrylic polymers, polyethyleneimine and cationic polymers; bentonite, silica Inorganic water-soluble polymers such as acid A1Mg (Vegum), laponite, hectorite, and silicic anhydride;

Gum arabic, carrageenan, karaya gum, tragacanth gum, carob gum, quince seed (quince), casein, dextrin, gelatin, sodium pectate, sodium alginate, methyl cellulose, ethyl cellulose, CMC, hydroxyethyl cellulose, hydroxypropyl cellulose, PV
A, thickeners such as PVM, PVP, sodium polyacrylate, carboxyvinyl polymer, locust bean gum, guar gum, tamarint gum, dialkyldimethyl ammonium sulfate, xanthan gum, aluminum magnesium silicate, bentonite, hectorite; talc, carion, Mica, sericite (sericite),
Muscovite, Phlogopite, Synthetic mica, Phlogopite, Biotite, Lithium 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 phosphate, fluoroapatite, hydroxyapatite, ceramic powder, metal soap (zinc myristate, calcium palmitate, aluminum stearate), inorganic such as boron nitride Powder, polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene powder, copolymer resin powder of styrene and acrylic acid, benzoguanamine resin powder, polytetrafluoroethylene Down powder, powdered ingredients, such as organic powders such as cellulose powder;

Inorganic white pigments such as titanium dioxide and zinc oxide; inorganic red pigments such as iron oxide (iron oxide) and iron titanate; inorganic brown pigments such as γ-iron oxide; and inorganic yellow pigments such as yellow iron oxide and loess Inorganic black pigments such as black iron oxide, carbon black, and lower titanium oxide; inorganic purple pigments such as mango violet and cobalt violet; chromium oxide;
Inorganic green pigments such as chromium hydroxide and cobalt titanate,
Inorganic blue pigments such as ultramarine blue, navy blue, etc., pearl pigments such as titanium oxide coated mica, titanium oxide coated bismuth oxychloride, titanium oxide coated talc, colored titanium oxide coated mica, bismuth oxychloride, fish scale foil,
Metal powder pigments such as aluminum powder and copper powder, Red No. 201, Red No. 202, Red No. 204, Red No. 205, Red No. 220, Red No. 226, Red No. 228
Organic pigments such as No. 4, Red No. 405, Orange No. 203, Orange No. 204, Yellow No. 205, Yellow No. 401 and Blue No. 404, Red No. 3, Red No. 104, Red No. 106, Red No. 22
No. 7, Red No. 230, Red No. 401, Red No. 505, Orange No. 205, Yellow No. 4, Yellow No. 5, Yellow No. 202, Yellow No. 203, Green No. 3, Blue No. 1, etc., zirconium, barium or aluminum lake Organic pigments, natural pigments such as chlorophyll, β-caroline, etc., titanium yellow,
Coloring agents such as carsamine and safflower red; and fragrance, water, alcohol, and the like can be appropriately added to the anti-aging skin external preparation of the present invention and the collagen cross-linking preventing skin external preparation of the present invention as needed. The specific prescription of the anti-aging skin external preparation of the present invention and the collagen external skin preparation of the present invention for preventing collagen cross-linking will be described in Examples below.

[0035]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the technical scope of the present invention.

[Test Example 1] Examination of cell damage preventing effect by ultraviolet rays Fibroblasts, one of the skin cells, were exfoliated from human skin pieces.
plant method [a method of culturing a small piece of tissue taken out of a living body on a plastic Petri dish and subculturing cells emigrated from the tissue piece ("Tissue Culture Technique" edited by The Japanese Society of Tissue Culture, 3-8 transplantation) Separation culture method, pp. 37-39, 1982)], and cultured in Dulbecco's modified Eagle's medium (DM
(EM medium).

Next, the cells were subjected to trypsin-EDTA treatment to prepare a cell suspension. The suspension was sown in a fixed number of culture dishes (Falcon 3001, 35 mm in diameter), and placed in a CO ₂ incubator (37 ° C., 37 ° C.). 5% CO ₂ ). After culturing for a certain period of time, the medium in the Petri dish was discarded, and the cells were washed twice with a phosphate buffer (1.5 ml / Petri dish). next,
A test sample and a phosphate buffer solution containing Ca ions and Mg ions (1.5 ml / dish) were added. Six of these samples were prepared, and three of them were irradiated with ultraviolet rays at 10 J / cm ² .

UV irradiation was performed using a Toshiba BLB lamp (TOSHIB
A FL20S ・ BLB UV-A region using a long-pass filter (WG
-335, manufactured by Shott). The irradiation amount of the ultraviolet rays was calculated from the average intensity and the irradiation time after measuring the ultraviolet intensity with a UV-RADIOMETER (manufactured by Eisai & Torex) in advance. The amount of ultraviolet rays actually irradiated on the cells was calculated in consideration of the absorption by a long-pass filter, a plastic Petri dish and a phosphate buffer (UV-A reduction rate 43%).
%).

Next, the phosphate buffer was discarded for both the non-irradiated and irradiated cells, the cells were washed twice with a phosphate buffer (1.5 ml / dish), and 1.5 ml of DMEM medium was added. Cultured. After culture, use the method of Labarca & Paigen (Analyt
ical Biochemistry, 102: 344-352, 1980).
The amount of NA was measured, the number of cells was converted by a calibration curve, the survival rate of the cells was determined by the following equation, and the average was evaluated as the protection rate.

[0040]

(Equation 1)

Table 1 shows the results of the test on the effect of preventing cell damage by this ultraviolet ray.

[Table 1]

From Table 1, it can be seen that N-acetylcysteine (I) exerts an excellent cytotoxicity-preventing effect at a specific concentration or higher, and the anti-aging skin preparation for external use of the present invention has the expected effect. It became clear that "prevention of skin aging" can be exerted through this effect of preventing cell damage.

0.001% by weight of the total skin external preparation
As described above, it is preferable to mix in a range of 0.1% by weight or less. If the amount is less than 0.0005, a satisfactory effect cannot be obtained. However, it was clarified that the effect was not increased in proportion to the increase in the blending amount.

Test Example 2 Investigation of Collagen Prevention Effect of Ultraviolet Ray Collagen (KOKEN) was maintained at 37 ° C. in a phosphate buffer at pH 7.4 so that the final concentration was 1 mg / ml. Fibers were formed and then 7.5 J /
Ultra-violet light (TOSHIBA FL20S / BLB lamp: VA area peak 365 nm) with an energy of ² cm2, a long-pass filter (WG-335, manufactured by Shott) from a position 16 cm from the petri dish
Went through. In addition, the irradiation amount of ultraviolet
Ultraviolet light intensity was measured by IOMETER (manufactured by Eisai & Torex) and calculated from the average intensity and irradiation time.

Various samples described later (Table 2) were allowed to coexist with collagen during ultraviolet irradiation. The amount of ultraviolet rays actually irradiated was calculated in consideration of absorption by a long-pass filter and a plastic petri dish (UV-A reduction rate 4
3%). The percentage of the irradiated collagen was measured by an electrophoresis method and a densitometer (Shimadzu Densitometer CS-9300PC). Then, the inhibition rate of collagen crosslinking was determined from the following equation.

[0046]

(Equation 2)

Table 2 shows the results of tests on the effect of preventing collagen crosslinking.

[Table 2]

From Table 2, it can be seen that N-acetylcysteine (I) exerts an excellent collagen cross-linking inhibitory effect at a specific concentration or higher, and is an anti-aging skin external preparation of the present invention and a collagen external prevention skin of the present invention. It has become clear that the intended effects of the agents can be sufficiently exerted.

It is preferable that N-acetylcysteine (I) is added in an amount of 0.001% by weight or more and 0.1% by weight or less of the whole collagen crosslinking inhibitor.
If the amount is less than 05, a satisfactory effect cannot be obtained.
It was also revealed that even if the amount exceeds 0.5% by weight, the effect corresponding to the increase in the amount of compounding cannot be expected to be enhanced.

Hereinafter, examples of various formulations of the anti-aging skin external preparation of the present invention and the collagen external skin preparation for preventing cross-linking of the present invention will be described as examples. Each of the anti-aging skin external preparations of the present invention and the collagen cross-linking prevention skin external preparation of the present invention exhibited an excellent cell damage preventing effect and a collagen cross-linking preventing effect leading to an excellent anti-aging effect.

[Example 10] Lotion by weight N-acetylcysteine (I) 0.05 Tocopherol acetate 0.01 Glycerin 4.0 1,3-butylene glycol 4.0 Ethanol 8.0 Polyoxyethylene (60) Hardened castor oil 0.5 Methyl paraben 0.2 Citric acid 0.05 Sodium citrate 0.1 Perfume 0.05 Purified water Residue

<Production method> N-acetylcysteine (I), citric acid, sodium citrate, glycerin, 1,
The 3-butylene glycol was dissolved. Separately, dissolve polyoxyethylene (60) hydrogenated castor oil, tocopherol acetate, fragrance and methyl paraben in ethanol,
This was added to the above-mentioned purified aqueous solution to solubilize and filtered to obtain a desired lotion.

Example 11 Cream% by weight setosteryl alcohol 3.5 squalane 40.0 beeswax 3.0 reduced lanolin 5.0 ethyl paraben 0.3 polyoxyethylene (20) sorbitan monomalmitic acid ester 2.0 stearin Acid monoglyceride 2.0 Sodium N-stearoylglutamate 0.5 2-Hydroxy-4-methoxybenzophenone 0.5 Octyl methoxycinnamate 1.0 Retinol acetate 2.0 Evening primrose oil 0.05 Fragrance 0.03 N-acetylcysteine (I) 0.1 Polyethylene glycol 1500 5.0 Purified water residue

<Production method> Cetostearyl alcohol, squalane, beeswax, reduced lanolin, ethyl paraben, polyoxyethylene (20) sorbitan monopalmitate, stearic monoglyceride, sodium N-stearoyl glutamate, 2-hydroxy-4-methoxybenzophenone Octyl methoxycinnamate, retinol acetate, evening primrose oil and fragrance were heated and dissolved (oil phase), N-acetylcysteine (I) and polyethylene glycol 1500 were dissolved in purified water and kept at 70 ° C. (aqueous phase). The oil phase was added to the aqueous phase with stirring. This was subjected to a homomixer treatment to make the emulsified particles fine, and then rapidly cooled with stirring to obtain a desired cream.

Example 12 Emulsion Weight% 2-Ethylhexyl paradimethylaminobenzoate 0.1 Mono-2-ethylhexyl diparamethoxycinnamate 0.2 Stearic acid 1.5 Cetyl alcohol 0.5 Beeswax 2. 0 polyoxyethylene (10) monooleate 2.0 L-arginine 0.3 L-sodium glutamate 0.02 PCA-Na 0.05 N-acetylcysteine (I) 0.01 glycerin 3.0 ethanol 3. 0 Ethylparaben 0.3 Fragrance 0.03 Carboxyvinyl polymer 0.12 Purified water Residue

<Production method> N-acetylcysteine (I), L-arginine, L-sodium glutamate,
PCA-Na, propylene glycol, glycerin, ethanol and carboxyvinyl polymer were added, dissolved by heating, and kept at 70 ° C. (aqueous phase). On the other hand, other components were mixed, dissolved by heating and kept at 70 ° C. (oil phase). This oil phase was added to the above-mentioned aqueous phase to perform preliminary emulsification, and the mixture was uniformly emulsified with a homomixer. Thereafter, the mixture was rapidly cooled with stirring to obtain a desired emulsion.

Example 13 Foam Mask Weight% N-acetylcysteine (I) 0.05 Stearic acid 1.0 Behenic acid 1.0 Self-emulsifying glyceryl monostearate 1.5 Polyoxyethylene monostearate (5 ) Glycerin 2.5 batyl alcohol 1.5 fragrance 0.05 glycerin 5.0 1,3-butylene glycol 5.0 polyethylene glycol 1500 3.0 methyl paraben 0.1 potassium hydroxide 0.15 purified water residue liquefied petroleum gas 6.0 dimethyl ether 2.0

<Preparation method> N-acetylcysteine (I), glycerin, 1,3-butylene glycol, polyethylene glycol 1500, methyl paraben and potassium hydroxide were added to purified water and dissolved by heating at 70 ° C. Then, the mixture was uniformly mixed and filled in a container. Finally, liquefied petroleum gas and dimethyl ether were added as propellants to obtain the desired foam mask.

Example 14 Ointment% by weight N-acetylcysteine (I) 0.1 Octyl paradimethylaminobenzoate 4.0 Butylmethoxybenzoylmethane 0.5 Tocopherol acetate 0.5 Retinol palmitate 1.0 Stearyl alcohol 18.0 Mokuro 20.0 Polyoxyethylene (10) monooleate 0.25 Glycerin monostearate 0.3 Vaseline 32.0 Purified water Remainder

<Production method> N-acetylcysteine (I) was dissolved in purified water and kept at 70 ° C (aqueous phase). Other components were mixed and dissolved at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, and the mixture was uniformly emulsified with a homomixer and then cooled to obtain a desired ointment.

[0061]

Industrial Applicability According to the present invention, an anti-aging skin external preparation having an excellent anti-skin aging effect and a collagen cross-linking preventing skin external preparation having an excellent collagen cross-linking preventing effect are provided.

Claims (2)

[Claims] 1. A formula (I) HOOC-CHNH (OCCH 3) anti-aging external preparation for skin as an active ingredient N- acetylcysteine represented by CH ₂ SH (I). 2. A skin external preparation for preventing collagen cross-linking comprising N-acetylcysteine represented by the following formula (I) HOOC-CHNH (OCCH ₃ ) CH ₂ SH (I) as an active ingredient.