JP3459857B2 - External preparation for skin - Google Patents

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 a skin external preparation for preventing skin aging. More specifically, it belongs to the technical field of a skin external preparation capable of preventing skin aging by blending a specific aminoethyl compound and a seaweed extract.

[0002]

2. Description of the Related Art It is known that the skin becomes thinner as it ages and its metabolism decreases. As a cause of such skin aging, aging and the like are also important factors from a macroscopic point of view, but more direct causes include dryness, oxidation by active oxygen, etc., damage by ultraviolet rays (especially long-wavelength ultraviolet rays ( UVA) is known to reach the dermis, promote the formation of collagen crosslinks, and accelerate skin aging (described later)] and the like.

Conventionally, various means for preventing the above-mentioned aging of the skin have been adopted. For example, a skin external preparation containing various moisturizers to prevent skin aging due to drying, an external preparation containing an antioxidant such as vitamin E to prevent skin aging due to oxidation, or skin aging due to ultraviolet rays. In order to prevent the above, an external preparation and the like containing an ultraviolet absorber have already been provided. However, these conventional means for preventing skin aging are all means focusing on factors related to skin aging as a result, and they cannot leave the "coping therapy" range, and obtain a sufficient skin aging prevention effect. It cannot be denied that it cannot be done. Therefore, there is currently a demand for the establishment of a “root-therapeutic” means for stopping a more direct phenomenon that promotes skin aging.

[0004]

As a more direct phenomenon of promoting skin aging, an increase in collagen crosslinks (hereinafter referred to as collagen crosslinks) in the dermis is known (Cutaneous AgingEdited by Albert M. Kligman a).
nd Yoshio Takasu University of Tokyo Pres, 263-27
4, 1988; Sugiyama T., Fujimoto D., Arai C. and H
asegawa M., Biomed Res 8, 349-351, 1987). That is, the various skin aging factors mentioned above, especially ultraviolet rays (especially,
With exposure to long-wavelength ultraviolet light (UVA) that easily reaches the dermis (for crosslinking of collagen by exposure to ultraviolet light, see “Fujimori E., FEBS Lett 235 (1-2), 98-102, 198).
8 ”), the proliferative activity of fibroblasts, which are the main cells in the dermis, and the synthesis / degradation function of collagen, etc. are reduced, and the turnover speed of this collagen, etc. is also slowed. It is presumed that these will undergo various modifications and denaturation, and the crosslinking of collagen in the skin will increase.

As this collagen crosslink increases,
The skin becomes less elastic, wrinkles and sagging increase, and the aging of the skin progresses. An object of the present invention is to provide a topical external preparation for skin that effectively prevents skin aging by establishing a “root therapeutic” means for suppressing the progress of collagen cross-linking.

[0006]

The present inventor has conducted extensive studies in view of the above problems. As a result, they have found that it is possible to solve the above-mentioned problems by using a skin external preparation containing a specific aminoethyl compound and a seaweed extract as an active ingredient. That is, in the present application, the present inventor provides the following inventions.

In claim 1, there is provided a skin external preparation comprising the following components (a) and (b). (A) One or two aminoethyl compounds represented by the formula NH ₂ CH ₂ CH ₂ X (I) (wherein, X is —SO ₂ H or —SO ₂ SH), as a whole skin external preparation. 0.001% by weight or more and 1.0% by weight or less, and (b) the seaweed extract is 0.01% by weight or more and 20.0% by weight or less of the whole skin external preparation.

In Claim 2, one or two aminoethyl compounds (I) are contained in the range of 0.01% by weight or more and 0.5% by weight or less of the total skin external preparation. 1. An external preparation for skin according to 1.

The skin external preparation according to claim 1 or 2, wherein the seaweed extract is contained in an amount of 0.01% by weight or more and 10.0% by weight or less of the total skin external preparation. provide.

2-Aminoethylthiosulfonic acid according to claim 4, wherein the aminoethyl compound (I) is one kind, and the one kind of aminoethyl compound (I) is the group X is —SO ₂ SH. The external preparation for skin according to any one of claims 1 to 3 is provided.

In claim 5, the aminoethyl compound (I) includes two kinds of 2-aminoethylthiosulfonic acid in which the group X is -SO ₂ SH and 2-aminoethylsulfinic acid in which the group X is -SO ₂ H. The external preparation for skin according to any one of claims 1 to 3, which comprises

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below. The external preparation for skin of the present invention contains an aminoethyl compound represented by the above formula (I). An aminoethyl compound represented by formula (I), that is, 2-aminoethylsulfinic acid (hypotaurine) in which X is —SO ₂ H, that is, a sulfinic acid group, and X is —SO ₂ SH, that is, a thiosulfonic acid group. -Aminoethylthiosulfonic acid (thiotaurine) is contained both in the main organs of many mammals including humans, such as the heart, brain, liver, etc., and is also contained in a large amount in foods that are ingested daily. Also,
No side effects such as skin irritation, itching or rash have been reported. Therefore, it is clear that there is no problem in safety even if the aminoethyl compound represented by the formula (I) is added to the skin external preparation of the present invention.

Further, these aminoethyl compounds (I)
Can be easily produced from a readily available thio compound such as cysteine by a commonly known method, and a commercially available product can be added to the external skin preparation of the present invention. By incorporating these aminoethyl compounds (I) in the external preparation for skin of the present invention, it is possible to greatly contribute to the expression of the desired effect in the external preparation for skin of the present invention through the action of suppressing collagen cross-linking.

That is, the external preparation for skin of the present invention suppresses collagen cross-linking, so that photoaging, which is a skin aging phenomenon caused by exposure to ultraviolet rays from the sun, is of course
It is possible to prevent deterioration of elasticity of the skin and generation of wrinkles and sagging due to aging of the skin, including suppression of progress of aging due to aging.

The blending amount of these aminoethyl compounds (I) in the external preparation for skin of the present invention should be appropriately changed depending on the kind or amount of other components to be added to the external preparation for skin of the present invention, and is generally defined. It shouldn't be,
It is generally compounded within the range of 0.001% by weight or more and 1.0% by weight or less of the entire skin external preparation of the present invention. When the compounding amount of the aminoethyl compound (I) in the external preparation for skin of the present invention is less than 0.001% by weight of the total external preparation for skin of the present invention, the desired effects described above are obtained through the collagen cross-linking inhibitory effect. It is not preferable because it becomes difficult to exert in. Further, even if the amount exceeds 1.0% by weight of the total external preparation for skin of the present invention, the above-mentioned effect corresponding to the increase in the amount added is no longer observed, which is not preferable.

From the balance between the expression strength of the above-mentioned effects and the blending amount, the aminoethyl compound (I) in the external preparation for skin of the present invention is generally contained in an amount of 0.01% by weight or more based on the whole external preparation for skin of the present invention. It is preferably blended in the range of 0.5% by weight or less.

0.001% by weight of the total skin external preparation of the present invention
As described above, when the blending amount is less than about 0.01% by weight, the effect of suppressing collagen cross-linking is often not sufficient only by blending the aminoethyl compound (I), and as a result, blending of other auxiliary components and the like. It tends to be necessary to increase the amount.

When the amount of the external preparation for skin of the present invention is more than 0.5% by weight and 1.0% by weight or less, the desired effect on the increase of the amount of aminoethyl compound (I) is obtained. The enhancement of the expression is slow, and rather the active ingredients of the present invention tend to exert a superior effect by positively blending other auxiliary ingredients.

The above-mentioned two aminoethyl compounds (I)
It is needless to say that each of them can be blended alone in the external preparation for skin of the present invention, but it is also possible to blend them in combination, and one kind of aminoethyl compound (I) is blended. It is recognized that the inhibition of collagen cross-linking is more enhanced when the two types are combined and blended than when the two types are combined. When two kinds of aminoethyl compounds (I) are both compounded in the external preparation for skin of the present invention, the compounding ratio of both external preparations for skin of the present invention is arbitrary and is not particularly limited.

The skin external preparation of the present invention further contains a seaweed extract. By incorporating a seaweed extract into the skin external preparation of the present invention, the desired effects of the skin external preparation of the present invention described above can be synergistically exerted by the various physiological actions of the seaweed component.

The type of seaweed extract that can be incorporated in the present invention can be incorporated in the skin external preparation of the present invention, and is particularly preferable as long as the above synergistic effect can be exerted in the skin external preparation of the present invention. Not limited. Therefore, although the seaweed extracts are listed below, it goes without saying that the seaweed extracts that can be incorporated into the skin external preparation of the present invention are not limited to these seaweed extracts.

The seaweed extract used in the present invention is, for example, an extract extracted from seaweeds belonging to the genus Hibamata belonging to the brown algae, the genus Kombu or the genus Tsunomata belonging to the red algae, the genus Suginori and the like. The method for extracting these seaweed extracts is not particularly limited, and hydrophilic organic solvents such as water and alcohol, mixed liquids of water and hydrophilic organic solvents, glycerin, 1,3-butylene glycol, etc. Can be extracted with a polyhydric alcohol or a mixed solution of water and a polyhydric alcohol. In addition, the extraction process can also be performed through a generally known process. Furthermore, it is of course possible to incorporate a commercial product of these seaweed extracts into the external preparation for skin of the present invention.

The amount of the seaweed extract to be blended can be appropriately changed depending on the dosage form of the skin external preparation of the present invention and the degree of anti-aging effect to be imparted. On the other hand, it is 0.001% by weight or more and 20% by weight or less, preferably 0.01% by weight or more and 10% by weight or less. If the blending amount is less than 0.01% by weight with respect to the entire skin external preparation of the present invention, the synergistic effect due to the sufficient blending of the seaweed extract tends not to be exhibited. Also,
Even if the amount exceeds 20% by weight of the total external preparation for skin of the present invention, the synergistic effect commensurate with the increase in the amount added tends not to be observed.

The external preparation for skin of the present invention containing the above-mentioned active ingredients can sufficiently exhibit the intended effect of suppressing skin aging. However, by blending other medicinal components as necessary, for the purpose of imparting the effect that the skin external preparation will generally exhibit, the addition of this other medicinal component to the skin external preparation of the present invention, The compounding is possible within a range that does not impair the intended effect of the present invention.

For example, imparting a moisturizing effect is useful for the purpose of preventing aging due to dry skin. In this case, 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-hydroxy. Moisturizers such as stearate, sodium lactate, bile salts, dl-pyrrolidone carboxylate salts, short-chain soluble collagen, diglycerin (EO) PO adducts, Isaioba rose extract, Achillea millefolium extract, Merrilot extract, etc. are used in the present invention. It is possible to mix it with a skin external preparation.

Providing an anti-ultraviolet effect is useful for suppressing photoaging due to excessive exposure to ultraviolet rays on the skin. In this case, 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 -4, 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-hydroxy-3-benzophenone ultraviolet absorbers such as carboxymethyl benzophenone; 2, 2'-hydroxy-5-methylphenyl benzotriazole, 2- (2 ^'- hydroxy-5'-t-octylphenyl) benzotriazole, 2- (2 ^'- hydroxy-5'-methylphenyl)
Benzotriazole ultraviolet absorbers such as benzotriazole; Ziani soil methane, 4-methoxy -4 ^'-t-
A long-wavelength ultraviolet absorber such as butyldibenzoylmethane (parsol A) can be added to the skin external preparation of the present invention.

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
Benzoic acid type 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 salicylate. , Homomenthyl salicylate, octyl salicylate, phenyl salicylate,
Salicylic acid-based UV absorbers such as benzyl salicylate and p-isopropanol phenyl salicylate; octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl-2,5-diisopropyl cinnamate, ethyl-2,4-diisopropyl cinnamate, methyl-
2,4-diisopropyl cinnamate, propyl-p-
Methoxycinnamate, 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- [methylbis (trimethylsiloxy) ) Silyl] butyl, cinnamic acid-based UV absorbers such as p-dimethoxycinnamic acid monoethyl ester; 3- (4'-
Camphor derivatives such as methylbenzylidene) -d, 1-camphor, 3-benzylidene-d, 1-camphor, 5- (3,3-dimethyl-2-norbornylidene) -3-penten-2-one; urocanic acid, urocanine Medium wavelength ultraviolet (UVB) absorbers such as acid ethyl ester, 2-phenyl-5-methylbenzoxazole and dibenzalazine can be added to the external skin preparation of the present invention.

Further, an ultraviolet blocking agent such as titanium oxide (TiO ₂ ), talc (MgSiO ₂ ), carmine (FeO ₂ ), bentonite, kaolin, zinc oxide (ZnO) can be added to the external skin preparation of the present invention. Is.

The imparting of a whitening effect is useful for the purpose of alleviating the adverse effects of ultraviolet rays on the skin. In this case, a whitening agent such as a placenta extract, glutathione, and Yukinoshita extract can be added to the external skin preparation of the present invention.

The imparting of an anti-inflammatory effect is useful for the purpose of alleviating the adverse effects of ultraviolet rays on the skin, as in the 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 added to the external skin preparation of the present invention.

Similarly, activators such as royal jelly, photosensitizer, cholesterol derivative, calf blood extract, and the like; nonyl acid warenylamide, nicotine for the purpose of alleviating the adverse effects of ultraviolet rays on the skin and suppressing the aging of the skin. Acid benzyl ester, nicotinic acid β-butoxyethyl ester, capsaicin, zingerone, cantharis tincture, ictamol, caffeine, tannic acid, α-borneol, nicotinic acid tocopherol, inositol hexanicotinate, cyclanderate, cinnarizine, tolazoline, acetylcholine , Verapamil, cepharanthin,
Blood circulation promoters such as γ-oryzanol; antiseborrheic agents such as sulfur and thiantol can be added to the external preparation for skin of the present invention.

In addition, for various purposes, oyster extract component, laurel extract component, shikon extract component, peony extract component, assembly extract component, birch extract component, sage extract component, loquat extract component, carrot extract component, aloe extract component, Mallow extract component, iris extract component, grape extract component, Yokuinin extract component, loofah extract component, lily extract component, saffron extract component, senkyu extract component, ginger extract component, Hypericum extract component, ononis extract component, rosemary extract component, Garlic extract ingredient,
Capsicum extract component, Isaibara extract component, Astragalus membranaceus extract component, Merrilot extract component, Chinpi,
It is also possible to incorporate a plant extract such as Japanese radish in the external preparation for skin of the present invention.

Further, in order to further impart the inherent effect of each vitamin, for example, the effect of suppressing skin aging, to the skin external preparation of the present invention, vitamin A oils such as vitamin A oil, retinol, retinol acetate; riboflavin; riboflavin butyrate, vitamin B ₂ such as flavin adenine nucleotide; pyridoxine hydrochloride, vitamin B ₆ such as pyridoxine dioctanoate; L-ascorbic acid, L
-Vitamin C such as ascorbic acid dipalmitate, L-ascorbic acid 2-sodium sulfate, L-ascorbic acid phosphate, DL-α-tocopherol-L-ascorbic acid diester dipotassium
Pantothenic acids such as calcium pantothenate, D-pantothenyl alcohol, pantothenyl ethyl ether, and acetyl pantothenyl ethyl ether; vitamin Ds such as ergocalciferol and cholecalciferol;
Nicotinic acid such as nicotinic acid, nicotinic acid amide and benzyl nicotinate; Vitamin Es such as α-tocopherol, tocopherol acetate, DL-α-tocopherol nicotinate, DL-α-tocopherol succinate; Others such as vitamin P and biotin The above vitamins can be incorporated into the external preparation for skin of the present invention.

The above-mentioned medicinal components are not limited to other medicinal components which can be incorporated into the external preparation for skin of the present invention. The medicinal effects corresponding to the other medicinal components listed above are not limited to the above. For example, Vitamin C can be used as a whitening component and also as an antioxidant aid. Further, the other medicinal ingredients listed above may be blended alone in the external preparation for skin of the present invention, or two or more medicinal ingredients may be blended in an appropriate combination according to the purpose. .

INDUSTRIAL APPLICABILITY The present invention can be widely applied to cosmetics, pharmaceuticals, quasi-drugs, etc. applied to the outer skin, and its dosage form is also an aqueous system, a solubilizing system, an emulsifying system, a powder system, an oil. A wide variety of dosage forms such as liquid type, gel type, ointment type, aerosol type, water-oil two-layer type, water-oil-powder three-layer type can be adopted. In other words, basic cosmetics can be widely applied to the above-mentioned various dosage forms in the form of facial cleansers, lotions, milky lotions, creams, gels, essences (cosmetics), packs and masks. Further, makeup cosmetics can be widely applied to forms such as foundations. Furthermore, as long as it is a drug or a quasi drug, it can be widely applied in the form of various ointments and the like. And, in these dosage forms and forms,
The form that the external preparation for skin of the present invention can take is not limited.

In the external preparation for skin of the present invention, generally known base components are blended widely depending on the desired dosage form and form as long as the blending thereof does not impair the intended effect of the present invention. You can

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, southern oil, castor oil, linseed oil. Oil, safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, teaseed oil, kaya oil, rice bran oil, cinnamon oil, Japanese kiri oil, jojoba oil, germ oil, triglycerin,
Liquid fats and oils such as glycerin trioctanoate and glycerin triisopalmitate; cocoa butter, coconut oil, horse fat, hardened coconut oil, palm oil, beef tallow, sheep fat, hardened beef tallow, palm kernel oil,
Solid fats and oils such as pork fat, beef bone fat, mokuro kernel oil, hydrogenated oil, beef leg oil, mokuro, hydrogenated castor oil; beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, ivotaro, whale wax, montan wax, nukarou, lanolin,
Kapok wax, lanolin acetate, liquid lanolin, sugar cane wax, lanolin fatty acid isopropyl, hexyl laurate, reduced lanolin, jojoba wax, hard lanolin,
Shellac wax, POE lanolin alcohol ether, P
Waxes such as OE lanolin alcohol acetate, POE cholesterol ether, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether; oils such as liquid paraffin, ozokerite, squalene, pristane, paraffin, ceresin, squalene, petrolatum, microcrystalline wax, etc. Hydrocarbon oils; lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, 12-
Hydroxystearic acid, undecylenic acid, tallic acid,
Isostearic acid, linoleic acid, linoleic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DH
Higher fatty acids such as A); lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol,
Linear alcohols such as myristyl alcohol, oleyl alcohol, and cetostearyl alcohol, monostearyl glycerin ether (batyl alcohol), 2-decyltetradecinol, lanolin alcohol, cholesterol, phytosterols, hexyldecanol, isostearyl alcohol, octyldodecanol, etc. Branched alcohols such as 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-hydroxystearylate, ethylene glycol di-2-ethylhexylate. , Dipentaerythritol fatty acid ester, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate, diisostearyl malate, glycerin di-2-heptylundecanoate, tri-2-ethylhexyl trimethylolpropane, triisostearate tri Methylol propane, tetra-2-ethylhexyl pentane erythritol, tri-2-ethylhexyl glycerin, triisostearate Trimethylol propane, cetyl-2
Ethyl hexanoate, 2-ethylhexyl palmitate, glycerin trimyristate, glyceride tri-2-heptylundecanoate, castor oil fatty acid methyl ester, 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-ethylhexyl sebacate, myristic acid 2-
Hexyldecyl, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, synthetic ester oils such as ethyl acetate, butyl acetate, amyl acetate, triethyl citrate; dimethylpolysiloxane, methyl Chain polysiloxanes such as phenylpolysiloxane and methylhydrogenpolysiloxane, cyclic polysiloxanes such as decamethylpolysiloxane, dodecamethylpolysiloxane, and tetramethyltetrahydrogenpolysiloxane, and silicone resins that form a three-dimensional network structure. , Silicones such as silicone rubber; base for soap, fatty acid soap such as sodium laurate, sodium palmitate, etc., higher alkyl sulfate ester salt such as sodium lauryl sulfate, K lauryl sulfate, P E triethanolamine lauryl sulfate, alkyl ether sulfate salts such as POE sodium lauryl sulfate, sodium lauroyl sarcosinate, etc. N- acyl sarcosinates, N- myristoyl -N-
Methyl taurine sodium, coconut oil fatty acid methyl tauride sodium, lauryl methyl tauride sodium and other higher fatty acid amide sulfonates, POE oleyl ether phosphate sodium, POE stearyl ether phosphate and other phosphate ester salts, di-2-ethylhexyl Sodium sulfosuccinate, monolauroyl monoethanolamide polyoxyethylene sodium sulfosuccinate, sulfosuccinates such as sodium lauryl polypropylene glycol sulfosuccinate, sodium linear dodecylbenzenesulfonate, triethanolamine linear dodecylbenzenesulfonate, linear dodecylbenzenesulfonic acid, etc. Alkylbenzene sulfonate, N-
Monosodium lauroyl glutamate, disodium N-stearoyl glutamate, N-myristoyl-L
-N-acyl glutamate such as monosodium glutamate, higher fatty acid ester sulfate such as hydrogenated coconut oil fatty acid glycerin sodium sulfate, sulfated oil 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 ester salt, higher fatty acid alkylolamide sulfate ester salt, lauroyl monoethanolamide sodium succinate, N-palmitoyl aspartate ditriethanolamine, sodium caseinate, etc. Anionic surfactants; alkyl trimethyl ammonium salts such as stearyl trimethyl ammonium chloride, lauryl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride Alkylpyridinium salts, such as alkyl dimethylammonium salts, poly (N, N'-dimethyl-3,5-methylenepiperidinium chloride), cetylpyridinium chloride, alkyl quaternary ammonium salts, alkyldimethylbenzylammonium salts, alkylisoxy Cationic surfactants such as norinium salts, dialkylmorphonium salts, POE alkylamines, alkylamine salts, polyamine fatty acid derivatives, amyl alcohol fatty acid derivatives, benzalkonium chloride, benzethonium chloride;
2-Undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc., imidazoline-based amphoteric interface Amphoteric surfactants such as activators, betaine-based surfactants such as 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaines, alkyl betaines, amidobetaines, sulfobetaines; sorbitan Monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate,
Sorbitan fatty acid esters such as sorbitan trioleate, penta-2-ethylhexyl diglycerol sorbitan, tetra-2-ethylhexyl diglycerol sorbitan, mono cottonseed oil fatty acid glycerin, monoerucic acid glycerin, sesquioleate glycerin, monostearate glycerin, α , α'-glyceryl pyroglutamate oleate, glycerol monostearate glycerin polyglycerin fatty acids such as malic acid, propylene glycol fatty acid esters such as propylene glycol monostearate, hydrogenated castor oil derivative, glycerin alkyl ether, polyoxyethylene Lipophilic nonionic surfactant such as methylpolysiloxane copolymer; PO
E sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, PO
POE sorbitan fatty acid esters such as E-sorbitan tetraoleate, POE-sorbit monolaurate, POE-sorbit monooleate, POE-sorbit pentaoleate, POE-sorbit monostearate, and other POE sorbit fatty acid esters, PO
POE glycerin fatty acid esters such as E-glycerin monostearate, POE-glycerin monoisostearate, POE-glycerin triisostearate, P
OE monooleate, POE distearate, POE monodioleate, POE fatty acid esters such as ethylene glycol distearate, POE lauryl ether,
POE oleyl ether, POE stearyl ether,
POE alkyl ethers such as POE behenyl ether, POE 2-octyldodecyl ether, POE cholestanol ether, POE octyl phenyl ether,
POE alkyl phenyl ethers such as POE nonyl phenyl ether and POE dinonyl phenyl ether, Pluronic types such as Bourronic, POE / POP cetyl ether, POE / POP 2-decyl tetradecyl ether, POE / POP monobutyl ether, POE
・ POE hydrogenated lanolin, POE / POP alkyl ethers such as POE / POP glycerin ether, tetra POE / tetra POP ethylenediamine condensates such as Tetronic, POE castor oil, POE hydrogenated castor oil, PO
E hydrogenated castor oil monoisostearate, POE hydrogenated castor oil triisostearate, POE hydrogenated castor oil monopyroglutamic acid monoisostearate diester, PO
E hydrogenated castor oil POE castor oil such as maleic acid hydrogenated castor oil derivative, POE beeswax lanolin derivative such as POE sorbit beeswax, alkanol amide such as coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, POE propylene glycol Fatty acid ester, POE alkylamine, POE fatty acid amide, sucrose fatty acid ester, PO
E Nonylphenyl formaldehyde condensates, hydrophilic nonionic surfactants such as alkylethoxydimethylamine oxide, trioleylphosphoric acid, etc .; preservatives such as ethylparaben, butylparaben; arabia gum, tragacanth gum, galactan, guar gum, carob gum, karaya gum, carrageenan , Pectin, agar, quince seed (quince), arge colloid (cassius extract),
Starch (rice, corn, potato, wheat), plant-based polymers such as glycyrrhizinic acid, xanthan gum, dextran, succinoglucan, microbial-based polymers such as pullulan, collagen, casein, albumin,
Natural water-soluble polymers such as animal polymers such as gelatin; starch-based polymers such as carboxymethyl starch and methyl hydroxypropyl starch Methyl cellulose, nitrocellulose, ethyl cellulose, methyl hydroxypropyl cellulose, hydroxyethyl cellulose, sodium cellulose sulfate, hydroxy Propyl cellulose,
Cellulosic polymers such as sodium carboxymethyl cellulose (CMC), crystalline cellulose, and cellulose powder,
Semi-synthetic water-soluble polymers such as alginic acid-based polymers such as sodium alginate and propylene glycol alginate; vinyl-based polymers such as polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, carboxyvinyl polymer (Carbopol), and alkyl-modified carboxyvinyl polymer. Polymer, polyethylene glycol 2
Polymers such as 000, 4000, 6000, polyoxyethylene-polyoxypropylene copolymer copolymers, sodium polyacrylate, polyethyl acrylate, polyacrylamide and other acrylic polymers, polyethyleneimine, Synthetic water-soluble polymer such as cationic polymer; bentonite, silicic acid A1Mg
(Veegum), laponite, hectorite, inorganic water-soluble polymers such as silicic acid; gum arabic, carrageenan, karaya gum, tragacanth gum, carob gum, quince seed (quince), casein, dextrin,
Gelatin, sodium pectate, sodium alginate, methylcellulose, ethylcellulose, CMC, hydroxyethylcellulose, hydroxypropylcellulose, PVA, PVM, PVP, sodium polyacrylate, carboxyvinyl polymer, locust bean gum, guar gum, tamarind gum, dialkyldimethylammonium sulfate. Thickeners such as cellulose, xanthan gum, magnesium aluminum silicate, bentonite, hectorite; talc, carion, mica, sericite, muscovite, phlogopite, synthetic mica, phlogopite, biotite, lithia mica, Permiculite, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, tan Sten acid metal salt, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate (calcined gypsum), calcium phosphate, fluorine apatite, hydroxyapatite, ceramic powder, metal soap (zinc myristate, calcium palmitate,
Aluminum stearate), inorganic powder such as boron nitride, polyamide resin powder (nylon powder), polyethylene powder, polymethylmethacrylate powder, polystyrene powder, copolymer resin powder of styrene and acrylic acid, benzoguanamine resin powder, polytetrafluorocarbon Powder components such as organic powders such as ethylene oxide and cellulose powder; inorganic white pigments such as titanium dioxide and zinc oxide; inorganic red pigments such as iron oxide (red iron oxide) and iron titanate; inorganic brown such as γ-iron oxide. -Based pigments, inorganic yellow pigments such as yellow iron oxide and loess, inorganic black pigments such as black iron oxide, carbon black and low order titanium oxide, inorganic purple pigments such as mango violet and cobalt violet, chromium oxide, chromium hydroxide , Inorganic green pigments such as cobalt titanate, inorganic blue pigments such as ultramarine blue and navy blue,
Titanium oxide coated mica, titanium oxide coated bismuth oxychloride, titanium oxide coated talc, colored titanium oxide coated mica, bismuth oxychloride, pearl pigments such as fish scale foil, metal powder pigments such as aluminum powder, copper powder, red 201, red 202
No., Red No. 204, Red No. 205, Red No. 220, Red No. 226, Red No. 228, Red No. 405, Orange No. 203
No. 204, Orange No. 204, Yellow No. 205, Yellow No. 401 and Blue No. 404 and other organic pigments, Red No. 3, Red No. 104,
Red 106, Red 227, Red 230, Red 40
No. 1, Red No. 505, Orange No. 205, Yellow No. 4, Yellow 5
No., Yellow No. 202, Yellow No. 203, Green No. 3, Blue No. 1, etc., organic pigments such as zirconium, barium or aluminum lake, natural pigments such as chlorophyll, β-caroline, etc., titanium yellow, cursamine, safflower red etc. Coloring agents and the like; further, fragrances, water, alcohols and the like can be appropriately added to the external preparation for skin of the present invention as necessary. The specific formulation of the external preparation for skin of the present invention will be described in Examples described later.

[0038]

EXAMPLES Next, the present invention will be described in more detail with reference to Examples and the like.
To explain. However, due to this, the technical scope of the present invention is
The enclosure is not to be construed as limiting. [Test Example] Crosslinking prevention effect of collagen by ultraviolet rays (1) First, obtain the cross-linking ratio of collagen by ultraviolet rays.
The method of setting the position will be described. Collagen from human placenta
Prepared by extraction with pepsin treatment and purification by salting out
(Nishihara T. and Miyata T., Collagen Synposium
3, 66-93,1962). And electrophoresis (Hayahi T. a
nd Nagai Y., J Biochem,86 (2), 453-459, 1962
 ), The purity of this collagen was measured to be 94%.
Met. Next, this extracted and purified collagen (final concentration
1 mg / ml) at 37 ° C in phosphate buffer pH 7.4.
Collagen fibers are formed by this, and various
Coexist sample with collagen, 7.0 J / cm²The Enel
Guy's UV rays (TOSHIBA FL20S / BLB lamp, UVA area)
Region, peak 365 nm) (UVA intensity: 1.4
mW / cm², Irradiation time: 90 minutes).

The collagen after irradiation was subjected to electrophoresis and a densitometer (fluorescence densitometer F-80, manufactured by Cosmo Co., Ltd.).
Analysis was performed according to 8), and the proportion of collagen crosslinked by the above-mentioned ultraviolet irradiation was measured. Then, the inhibition rate of collagen cross-linking by the addition of various samples described below was calculated from the following equation.

[0040]

[Equation 1]

(2) Next, 2-aminoethylthiosulfonic acid, which is one embodiment of the aminoethyl compound (I), and a seaweed extract belonging to the genus Hibamata are extracted with the amount of this 2-aminoethylthiosulfonic acid. Table 1 shows the test results for examining the collagen cross-linking formation inhibitory effect in the case of changing and combining. All% in the table mean% by weight (excluding the inhibition rate).

[0042]

[Table 1] Table 1

From the results shown in Table 1, the coexistence of 2-aminoethylthiosulfonic acid and the seaweed extract with collagen remarkably suppresses the formation of collagen cross-links, which are extremely deeply related to skin aging as described above. It became clear. That is, it was revealed that 2-aminoethylthiosulfonic acid and seaweed extract are extremely useful as active ingredients of the external preparation of the present invention.

In order to reliably achieve a collagen cross-linking formation inhibition rate of 50% or more by adding 2-aminoethylthiosulfonic acid, it is necessary to add 0.002% of all test system components.
It is necessary to add 1% by weight or more of 2-aminoethylthiosulfonic acid to the system, and the amount of 2-aminoethylthiosulfonic acid added to the system is less than 0.001% by weight of all test system components. Then, it became clear from Test Example 7 and Test Example 8 that it becomes difficult to effectively suppress the collagen cross-linking.

On the contrary, if the amount of 2-aminoethylthiosulfonic acid added to the system exceeds 1.0% by weight of the total components of the test system, further formation of collagen crosslinks is suppressed even if the amount is further added. It was also revealed in Test Example 1 that the improvement in the rate cannot be expected.

3) Further, Table 2 shows the test results for examining the inhibitory effect on the formation of collagen crosslinks when the amounts of the seaweed extracts were changed and combined. All% in the table mean% by weight (excluding the inhibition rate).

[0047]

[Table 2] Table 2

From the results shown in Table 2, the coexistence of 2-aminoethylthiosulfonic acid and the seaweed extract with collagen in the same manner as the results shown in Table 1 makes it extremely deep in skin aging as described above. It was revealed that the formation of associated collagen crosslinks was significantly suppressed.

In order to achieve a synergistic inhibition rate of collagen cross-link formation by adding a seaweed extract belonging to the genus Hibamata, 0.01% by weight or more of the total amount of the test system components is added to the system. It is necessary to add, and the amount of seaweed extract added to the system is 0.01% by weight based on the whole test system components.
It was revealed by Test Example 17 and Test Example 18 that when it is less than 100%, it tends to be difficult to synergistically suppress collagen crosslinking.

On the contrary, the amount of seaweed extract added to the system is
If the content exceeds 20.0% by weight of the total components of the test system, it is not possible to expect a further improvement in the collagen crosslink formation inhibition rate even if additional blending is further performed.
Revealed by.

(3) Examination of Synergistic Effect when Aminoethyl Compound (I) is Combined and Combined In addition to 2-aminoethylthiosulfonic acid described above, another embodiment of aminoethyl compound (I), 2- Table 3 shows the test results examined for the case of adding aminoethylsulfinic acid in combination with the test system. All% in the table mean% by weight (excluding the inhibition rate).

[0052]

[Table 3] Table 3

In Table 3, by comparing Test Example 19 with Control Example 4 or Control Example 5 and with Test Example 20 and Test Example 15 in Table 2 above, combining two kinds of aminoethyl compounds (I) In that, the effect of suppressing the formation of collagen crosslinks, which is superior to the case of using only one kind of aminoethyl compound (I), is exerted, and two kinds of aminoethyl compound (I) are combined to further produce a seaweed extract. It was clarified that the very effective suppression effect of the formation of collagen cross-links was exhibited by blending.
Hereinafter, compounding examples of the external preparation for skin of the present invention in various dosage forms will be described as examples. In addition, each external preparation for skin exhibited excellent anti-aging effect.

[Example 1] Skin toner% by weight (1) 2-aminoethylthiosulfonic acid 0.05 (2) Seaweed extract (Hibamata) 1.0 (3) Tocopherol acetate 0.01 (4) Glycerin 4.0 (5) 1,3-butylene glycol 4.0 (6) Ethanol 8.0 (7) Polyoxyethylene (60) Hydrogenated castor oil 0.5 (8) Methylparaben 0.2 (9) Citric acid 0 .05 (10) Sodium citrate 0.1 (11) Perfume 0.05 (11) Purified water Residue <Production method> Purified water was added to 2-aminoethylthiosulfonic acid,
Seaweed extract, citric acid, sodium citrate, glycerin,
The 1,3-butylene glycol was dissolved. Separately, polyoxyethylene (60) hydrogenated castor oil, tocopherol acetate, perfume, and methylparaben were dissolved in ethanol, and this was added to the purified aqueous solution to solubilize it, followed by filtration to obtain a lotion.

Example 2 Cream Weight% (1) Cetostearyl Alcohol 3.5 (2) Squalane 40.0 (3) Beeswax 3.0 (4) Reduced Lanolin 5.0 (5) Ethylparaben 0.3 (6) Polyoxyethylene (20) sorbitan monopalmitate 2.0 (7) Stearic acid monoglyceride 2.0 (8) Sodium N-stearoylglutamate 0.5 (9) 2-hydroxy-4-methoxybenzophenone 0. 5 (10) Octyl methoxycinnamate 1.0 (11) Retinol acetate 2.0 (12) Evening primrose oil 0.05 (13) Perfume 0.03 (14) 2-Aminoethylsulfinic acid 0.1 (15) Seaweed extract (genus Tsunomata) 5.0 (16) Polyethylene glycol 1500 5.0 (17) Purified water Residue <Production method Cetostearyl alcohol, squalane, beeswax, reduced lanolin, ethylparaben, polyoxyethylene (20) sorbitan monopalmitic acid ester, stearic acid monoglyceride, sodium N-stearoylglutamate, 2-hydroxy-4-methoxybenzophenone, octyl methoxycinnamate , Retinol acetate, evening primrose oil, and fragrance were dissolved by heating (oil phase). On the other hand, 2-aminoethylsulfinic acid, seaweed extract, and polyethylene glycol 1500 were dissolved in purified water and kept at 70 ° C (aqueous phase). Then, the above oil phase was added to this aqueous phase while stirring. After homogenizing with a homomixer to make the emulsified particles fine, the mixture was rapidly cooled with stirring to obtain a cream.

Example 3 Emulsion weight% (1) 2-Ethylhexyl paradimethylaminobenzoate 0.1 (2) Mono-2-ethylhexyl diparamethoxycinnamic acid 0.2 (3) Stearic acid 1.5 (4) Cetyl alcohol 0.5 (5) Beeswax 2.0 (6) Polyoxyethylene (10) Monooleate 2.0 (7) L-arginine 0.3 (8) L-sodium glutamate 0.02 (9) PCA-Na 0.05 (10) 2-aminoethylsulfonic acid 0.2 (11) 2-aminoethylsulfinic acid 0.01 (12) Seaweed extract (Kelp genus) 10.0 (13) Glycerin 3.0 (14) Ethanol 3.0 (15) Ethylparaben 0.3 (16) Perfume 0.03 (17) Carboxyvinyl polymer 0.12 (18) Purified water Excess <method> in purified water 2-aminoethyl sulfonic acid, 2-aminoethyl sulfinic acid, L- arginine, L- sodium glutamate, PCA-Na, glycerin, ethanol, and dissolved by heating by adding carboxyvinyl polymer 70
It was kept at ℃ (water phase). On the other hand, other components were mixed, dissolved by heating and kept at 70 ° C. (oil phase). Next, this oil phase was added to the above aqueous phase for preliminary emulsification, and the mixture was uniformly emulsified with a homomixer. Then, it was rapidly cooled with stirring to obtain an emulsion.

Example 4 Foam Mask Weight% (1) 2-Aminoethylthiosulfonic Acid 1.0 (2) Seaweed Extract (Cercisaceae) 0.1 (3) Stearic Acid 1.0 (4) Behenin Acid 1.0 (5) Self-emulsifying glycerin monostearate 1.5 (6) Polyoxyethylene monostearate (5) Glycerin 2.5 (7) Batyl alcohol 1.5 (8) Perfume 0.05 (9 ) Glycerin 5.0 (10) 1,3-butylene glycol 5.0 (11) Polyethylene glycol 1500 3.0 (12) Methylparaben 0.1 (13) Potassium hydroxide 0.15 (14) Purified water Residual (15 ) Liquefied petroleum gas 6.0 (16) Dimethyl ether 2.0 <Production method> 2-aminoethylthiosulfonic acid, seaweed extract, glycerin, 1,3-butane in purified water Glycol,
Polyethylene glycol 1500, methylparaben, and potassium hydroxide were added, and the mixture was dissolved by heating at 70 ° C (aqueous phase).
On the other hand, other components were mixed, heated and dissolved, and then maintained at 70 ° C. (oil phase). Next, this oil phase was added to the above aqueous phase and mixed uniformly, and then cooled. This uniformly mixed mixture was filled in a container, and finally liquefied gas and dimethyl ether were added as a propellant to obtain a foam mask.

Example 5 Ointment wt% (1) 2-Aminoethylthiosulfonic acid 0.1 (2) 2-Aminoethylsulfinic acid 1.0 (3) Seaweed extract (Hibamata) 20.0 ( 4) Octyl paradimethylaminobenzoate 4.0 (5) Butylmethoxybenzoylmethane 0.5 (6) Tocopherol acetate 0.5 (7) Retinol palmitate 1.0 (8) Stearyl alcohol 18.0 (9) Mokurou 20.0 (10) Polyoxyethylene (10) monooleate 0.25 (11) Glycerin monostearate 0.3 (12) Vaseline 32.0 (13) Purified water Residue <Production method> 2 in purified water -Aminoethylthiosulfonic acid, 2
-Dissolve aminoethylsulfinic acid, seaweed extract 70
It was kept at ℃ (water phase). On the other hand, other components were mixed and dissolved at 70 ° C. (oil phase). Next, this oil phase was added to the above aqueous phase, and the mixture was uniformly emulsified with a homomixer and then cooled to obtain an ointment.

[0059]

INDUSTRIAL APPLICABILITY According to the present invention, there is provided an anti-aging skin external preparation for preventing skin aging.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁷ Identification code FI A61P 43/00 A61P 43/00 // (A61K 31/185 A61K 35:80 35:80) (56) Reference JP-A-7 -233046 (JP, A) JP-A-6-80964 (JP, A) JP-A-7-126148 (JP, A) JP-A-7-101871 (JP, A) JP-A-6-9422 (JP, A) ) JP-A-6-24937 (JP, A) JP-A-61-69707 (JP, A) JP-A-8-119849 (JP, A) JP-A-9-95414 (JP, A) (58) Field (Int.Cl. ⁷ , DB name) A61K ^7/ 00-7/50

Claims (5)

(57) [Claims] 1. A skin external preparation comprising the following components (a) and (b). (A) One or two aminoethyl compounds represented by the formula NH ₂ CH ₂ CH ₂ X (I) (wherein, X is —SO ₂ H or —SO ₂ SH), as a whole skin external preparation. 0.001% by weight or more and 1.0% by weight or less, and (b) the seaweed extract is 0.01% by weight or more and 20.0% by weight or less of the whole skin external preparation. 2. One or two aminoethyl compounds (I)
The external preparation for skin according to claim 1, which comprises 0.01% by weight or more and 0.5% by weight or less of the entire external preparation for skin. 3. A seaweed extract is added to 0.01% of the total skin external preparation.
The external preparation for skin according to claim 1 or 2, which is contained in the range of not less than 10% by weight and not more than 10.0% by weight. 4. An aminoethyl compound (I) is one kind,
And, the one aminoethyl compound (I) is a group X is -SO ₂ SH is a 2-aminoethyl-thio acid, the skin external preparation according to any one of claims 1 to 3. 5. The aminoethyl compound (I) wherein the group X is --S.
Is O ₂ SH and 2-aminoethyl-thio acid, consists of two 2-aminoethyl sulfinic acid in the same -SO ₂ H, skin external preparation according to any one of claims 1 to 3.