JPH107541A - Skin lotion - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin lotion which has the excellent action to delete active oxygen species and is useful for improvement and prevention of the senile change in skin, for example, skin roughening, wrinkles, spots and stains caused by the oxidation stress. SOLUTION: This skin lotion contains, as active ingredients, one or more of lipoic acid, its salts and derivatives, vitamin A and its derivatives, carotenoides, riboflavin and its derivatives, vitamin B6 , their salts and derivatives, cobalamins, vitamin C, its salts and derivatives, vitamin E and its derivatives, vitamin K, adenosine and its derivatives, flavonoids and tannins in amounts of 0.01-10wt.%, respectively. These active ingredients can be formulated to an external preparation for skin, a skin cosmetic or a make-up cosmetic. When applied to skin, this preparation can effectively delete active oxygen species exogenously and endogenously formed in skin and improve senile changes caused by the oxidation stress through the activation of in vivo antioxidation mechanism such as the endogenous increase in glutathione level.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin which has a synergistically enhanced activity for eliminating active oxygen species such as superoxide, hydroxyl radical and peroxide, improves and prevents roughening and aging of the skin, and has an excellent whitening effect. About.
More specifically, in addition to one or more of lipoic acid, salts and derivatives thereof, vitamin A and derivatives thereof, carotenoids, riboflavin and derivatives thereof, vitamin B ₆ , salts and derivatives thereof, cobalamin, One or two selected from the group consisting of vitamin C, salts and derivatives thereof, vitamin E and derivatives thereof, vitamin K, adenosine and derivatives thereof, flavonoids and tannins
The present invention relates to an external preparation for skin comprising at least one species.

[0002]

2. Description of the Related Art As the harmful effects of oxidative stress caused by ultraviolet rays and endogenous oxygen on skin become apparent, application of substances having antioxidant activity to external preparations for skin has been studied. Representative examples of these antioxidant substances include antioxidant vitamins such as vitamin Es and vitamin Cs.

[0003] Lipoic acid is also a vitamin-like substance that exhibits a peroxide-eliminating action by being reduced in vivo. Techniques for applying this lipoic acid to an external preparation for skin are also disclosed (JP-A-62-175415), a whitening agent (JP-A-63-8315, JP-B-63-44123), and a hair restorer (JP-B-3-27524). Alternatively, an anti-dandruff agent (Japanese Unexamined Patent Publication No.
145507) is also known.

[0004] However, the above antioxidant vitamins are unstable to light and oxidizing agents, and even derivatives having improved stability do not have sufficient antioxidant activity. In order to obtain a sufficiently effective effect, a considerably high concentration is required, and depending on the dosage form of the external preparation, formulation may be difficult due to solubility problems, or the stability of the preparation may be adversely affected.

[0005]

Accordingly, the present invention has an excellent active oxygen species elimination effect only by containing a low concentration of an antioxidant substance which does not affect the preparation stability of an external preparation. Skin roughness and wrinkles caused by oxidative stress,
It is an object of the present invention to provide an external preparation for skin having an effect of improving, preventing and whitening skin aging symptoms such as spots.

[0006]

Various studies have been made to solve the above-mentioned problems. In addition to one or more of lipoic acid, its salts and derivatives, vitamin A and its derivatives, carotenoids , riboflavin and its derivatives, vitamin B _6, their salts and derivatives, cobalamin compounds, vitamin C, salts and derivatives thereof, vitamin E and derivatives thereof, vitamin K, adenosine and derivatives thereof, the group consisting of flavonoids and tannins It has been found that by containing one or more selected from the group, the action of eliminating active oxygen species is synergistically improved. As a result, one or more kinds of the lipoic acid and the like and vitamin A
One or two or more of these compounds can be combined with each other at a low concentration that does not affect the stability of the external preparation for skin. I was able to demonstrate.

The lipoic acid salts and derivatives used in the present invention include sodium salts, potassium salts, alkyl esters, alkenyl esters, amides, and reduced dihydrolipoic acids and dihydrolipoamides. Alternatively, two or more kinds are selected and used. In particular, lipoic acid alkyl esters, alkenyl esters, amides,
Dihydrolipoic acid and dihydrolipoamide are preferred.

Among the physiologically active substances contained in combination with the lipoic acids in the present invention, vitamin A includes retinol, its ester, retinal, retinoic acid, its ester, 3-dehydroretinol, its ester, Preferred examples include -dehydroretinal, 3-dehydroretinoic acid and esters thereof. In addition to the above, complexes with water-soluble vitamins and α-hydroxy acids (JP-A-8-73338 and JP-A-8-73312) can also be used.

As carotenoids, α-carotene,
β-carotene, γ-carotene, lycopene, lutein, violaxanthin, spiriroxanthin, spheroidene,
Astaxanthin and the like are mentioned as preferable ones, and one or two or more kinds are selected from these and used.

[0010] Riboflavin is a water-soluble vitamin which is referred to as vitamin B _2. Derivatives thereof include flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN).
Select and use seeds.

Examples of vitamin B ₆ and salts thereof include pyridoxine, pyridoxal, pyridoxamine and salts thereof, and one or more of these are selected and used.

[0012] As cobalamin compound is cyanocobalamin is vitamin B _12, and methylcobalamin is related compounds, adenosylcobalamin, hydroxocobalamin, Aqua cobalamin and the like, to select one or more from these Used.

As vitamin C, its salts and derivatives,
Ascorbic acid, dehydroascorbic acid and salts thereof, ascorbic acid phosphate, phosphatidyl ascorbic acid and salts thereof are preferred. Further, a complex with tocopherol and astaxanthin (JP-A-63-139114, International Publication 92/92)
07544, JP-A-8-73311) can also be used.

Vitamin E and derivatives thereof include:
Preferred are α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, and acetates and nicotinates thereof, and one or more of these are selected and used. Α-tocotrienol, β-tocotrienol, γ-tocotrienol
In addition to tocotrienol and δ-tocotrienol, complexes with α-hydroxy acids (JP-A-6-279258) and the like can also be used.

Examples of vitamin K include phylloquinone, menaquinone and menadione, and one or more of these can be selected and used.

As adenosine derivatives, vitamin L
_{2 '} , adenosine monophosphate (A) involved in oxidative phosphorylation and stress response
MP), cyclic adenosine monophosphate (c-AMP), adenosine diphosphate (ADP) and adenosine triphosphate (AT
P), and one or more of these are selected and used.

Examples of flavonoids include catechins, hesperidin and rutin known as vitamin P, hesperitin having a vitamin P-like action, quercetin,
Preference is given to eriodictyol, eriodictin, epicatechin and the like, and one or more of these are selected and used.

The tannins include condensed tannins in which a flavanol skeleton is polymerized, hydrolyzed tannins in which aromatic organic acids such as gallic acid and ellagic acid are formed by hydrolysis, and these are sugar-depside-bonded, and tannic acids. M-galloyl gallic acid, and one or more of these can be selected and used. Hamamellitannin and tea tannin are particularly preferred from the viewpoint of the effect of eliminating active oxygen species.

In the present invention, the lipoic acid one or two or more, and vitamin A, carotenoids, riboflavin, vitamin B ₆ such cobalamin, vitamin C, vitamin E, vitamin K compound, One or two selected from adenosines, flavonoids and tannins
The species or more can be contained by directly dissolving them in an aqueous or oily solvent, but they can also be incorporated into micelles by a surfactant, or microcapsules or liposomes. The appropriate amount of each of these external preparations for skin is about 0.01 to 10.0% by weight.

In the present invention, oils, polyhydric alcohols, polysaccharides, water-soluble substances, etc. are used as long as they do not adversely affect the activity of antioxidant substances such as lipoic acids and vitamin A which are constituents of the present invention. Contains other commonly used skin external agents or cosmetic ingredients such as polymers, surfactants, ultraviolet absorbers, antioxidants, antimicrobial preservatives, anti-inflammatory agents, biologically active substances, fragrances, etc. Can also.

[0021]

The external preparation for skin according to the present invention, when applied to the skin, effectively eliminates exogenous and endogenous reactive oxygen species generated in the skin, and further increases endogenous glutathione levels. Through activation of the antioxidant mechanism in vivo,
Improves aging symptoms caused by oxidative stress in the skin such as rough skin and wrinkles, and further suppresses its progress. In addition, it also improves skin spots caused by sunburn and aging caused by ultraviolet rays, and prevents the occurrence of such spots.

[0022]

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a lotion, an emulsion,
As an external preparation for skin in the form of gels, creams, ointments, etc.
It can also be used as a skin cosmetic such as a lotion, an emulsion, a cream, a massage agent, a pack, and the like, and a makeup cosmetic such as an emulsion or a creamy foundation.

[0023]

EXAMPLES The present invention will be described in more detail with reference to Examples.

[Example 1] Lotion for skin (1) Ethanol 10.0 (wt%) (2) Hydroxyethylcellulose 1.0 (3) Ascorbic acid-encapsulated liposome 5.0 (encapsulation rate: 3.0% by weight) (4) Lipoic acid 1.0 (5) Purified water 83.0 Production method: After mixing (1), (2), (4) and (5) to make uniform,
Add and disperse (3).

Example 2 Emulsion for skin (1) Stearic acid 0.2 (% by weight) (2) Cetanol 1.5 (3) Vaseline 3.0 (4) Liquid paraffin 7.0 (5) Polyoxy Ethylene (10E.O.) monooleic acid 1.5 ester (6) Tocopherol acetate 5.0 (7) Lipoic acid methyl ester-encapsulated liposome 10.0 (encapsulation rate; 2.5% by weight) (8) Glycerin 5. 0 (9) Methyl parahydroxybenzoate 0.1 (10) Triethanolamine 1.0 (11) Purified water 65.7 Production method: Mix the oil phase components (1) to (6) and heat to dissolve uniformly And maintain at 70 ° C. On the other hand, the aqueous phase components (8) to (11) are mixed and heated to be uniform, and the temperature is set to 70 ° C. The oil phase component is gradually added to the aqueous phase component while stirring to emulsify,
After cooling, add (7) and disperse.

Example 3 Skin Gel (1) Dipropylene glycol 10.0 (% by weight) (2) Carboxyvinyl polymer 0.5 (3) Potassium hydroxide 0.1 (4) Methyl paraoxybenzoate 0.1 (5) Magnesium ascorbic acid phosphate ester 4.0 (6) Liposomes containing tocopherol nicotinate 4.0 (encapsulation rate: 3.5% by weight) (7) Liposomes containing lipoic acid 5.0 (encapsulation rate) 2.5% by weight) (8) Purified water 76.3 Production method: After dissolving (2) uniformly in (8), dissolve (4) in (1) and then add (3) (5)-(7)
Is added and dissolved or dispersed.

Example 4 Skin Cream (1) Beeswax 6.0 (% by weight) (2) Cetanol 5.0 (3) Reduced Lanolin 8.0 (4) Squalane 37.5 (5) Glyceryl fatty acid ester 4.0 (6) Lipophilic glyceryl monostearate 2.0 (7) Polyoxyethylene (20E.O.) sorbitan 5.0 Monolaurate (8) Dihydrolipoic acid 1.0 (9) Retinol palmitic acid Ester 1.0 (10) Propylene glycol 5.0 (11) Methyl parahydroxybenzoate 0.1 (12) Purified water 25.4 Production method: Mix and dissolve oil phase components (1) to (7) to 75 Heat to ° C. On the other hand, the aqueous phase components (10) to (12) are mixed and dissolved and heated to 75 ° C. Next, the oil phase component is added to the water phase component and pre-emulsified, and then uniformly emulsified by a homomixer. After cooling, (8) and (9) are added and mixed at 40 ° C.

Example 5 Oil-in-water emulsion ointment (1) White petrolatum 25.00 (% by weight) (2) Stearyl alcohol 25.00 (3) Glycerin 12.00 (4) Sodium lauryl sulfate 1.00 (5) Lactic acid tocopherol phosphodiester 0.05 (6) Retinoic acid 0.50 (7) Lipoic acid ethyl ester 0.25 (8) Dihydrolipoamide 0.25 (9) Methyl parahydroxybenzoate 0.10 (10 ) Ascorbic acid phosphate magnesium salt 0.10 (11) Purified water 35.75 Production method: Mix and dissolve the oil phase components of (1) to (5) to make uniform,
Heat to 75 ° C. On the other hand, the aqueous phase components (9) and (11) were mixed and dissolved, heated to 75 ° C., and the oil phase component was added thereto to emulsify. ) And (10) are added and mixed.

Example 6 Lotion (1) Ethanol 10.00 (% by weight) (2) 1,3-butylene glycol 5.00 (3) Methyl parahydroxybenzoate 0.10 (4) β-carotene 0 0.02 (5) Sodium lipoate 0.02 (6) Fragrance 0.10 (7) Purified water 84.76 Production method: (1) to (6) are sequentially added to (7) and uniformly mixed and dissolved .

Example 7 Emulsion (1) Squalane 5.0 (% by weight) (2) Vaseline 2.0 (3) Beeswax 0.5 (4) Sorbitan sesquioleate 0.8 (5) Polyoxy Ethylene (20E.O.) Sorbitan 1.2 Monolaurate (6) Propylene glycol 5.0 (7) 1.0% by weight aqueous solution of carboxyvinyl polymer 20.0 (8) Potassium hydroxide 0.1 (9) Paraoxy Methyl benzoate 0.1 (10) Adenosine triphosphate 0.1 (11) Sodium dihydrolipoate 0.1 (12) Fragrance 0.1 (13) Purified water 65.0 Production methods: (1) to (5) The oil phase components are mixed and heated to 70 ° C. On the other hand, the aqueous phase components (6), (9) and (13) were mixed and heated to 70 ° C., and the oil phase was added thereto for pre-emulsification, and then (7) was added and uniformly mixed. Later, add (8) to neutralize,
Emulsify uniformly with a homomixer and cool. After cooling, 4
At 0 ° C., add (10) to (12) and mix uniformly.

[Example 8] Moisturizing cream (oil-in-water type) (1) Stearyl alcohol 6.0 (% by weight) (2) Stearic acid 2.0 (3) Hydrogenated lanolin 4.0 (4) Squalane 9. 0 (5) octyl dodecanol 10.0 (6) polyoxyethylene (25E.O.) cetyl alcohol 3.0 ether (7) glyceryl monostearate 2.0 (8) 1,3-butylene glycol 6. 0 (9) Methyl parahydroxybenzoate 0.1 (10) Hamametannin 0.1 (11) Potassium lipoate 0.3 (12) Fragrance 0.1 (13) Purified water 57.4 Production method: (1)- The oil phase component of (7) is mixed and heated to 70 ° C. On the other hand, the aqueous phase components of (8), (9) and (13) were mixed and heated to 70 ° C., and the oil phase was added thereto to emulsify. After cooling, (10) to (10) Add 12) and mix uniformly.

[Example 9] Emollient cream (water-in-oil type) (1) Liquid paraffin 30.0 (% by weight) (2) Microcrystalline wax 2.0 (3) Vaseline 5.0 (4) Diglyceryl geo Maleic ester 5.0 (5) Sodium L-glutamate 1.6 (6) L-serine 0.4 (7) Propylene glycol 3.0 (8) Methyl parahydroxybenzoate 0.1 (9) Rutin 0.2 (10) Lipoic acid amide 0.5 (11) Fragrance 0.1 (12) Purified water 52.1 Production method: (5) and (6) are dissolved in a part of (12) to 50 ° C.
Add slowly to (4) heated to 0 ° C. with stirring. This was previously mixed and uniformly dispersed in (1) to (3), which were heated and dissolved at 70 ° C., and (7) and (8) were dissolved in the remainder of (12) and heated to 70 ° C. Add while stirring and emulsify with a homomixer. After cooling, (9) to (11) are added and mixed at 40 ° C.

Example 10 Makeup Base Cream (1) Stearic acid 12.00 (% by weight) (2) Cetanol 2.00 (3) Self-emulsifying glyceryl monostearate 2.00 (4) Vitamin K 0.25 (5) Propylene glycol 10.00 (6) Potassium hydroxide 0.30 (7) Methyl parahydroxybenzoate 0.10 (8) Sodium lipoate 0.25 (9) Fragrance 0.10 (10) Purification Water 71.50 (11) Titanium dioxide 1.00 (12) Bengala 0.10 (13) Yellow iron oxide 0.40 Production method: (11) to (13) are kneaded with (5), and this is kneaded with (6), (7), (10)
, Mixed and heated to 70 ° C. On the other hand, (1)
The oil phase components (4) to (4) are mixed and heated to 70 ° C., and the mixture is added to the aqueous phase with stirring to emulsify. After emulsification, cool and add (8) and (9) at 40 ° C and mix.

Example 11 Emulsion Foundation (1) Stearic acid 2.4 (% by weight) (2) Propylene glycol monostearate 2.0 (3) Cetostearyl alcohol 0.2 (4) Liquid lanolin 0 (5) Liquid paraffin 3.0 (6) Isopropyl myristate 8.5 (7) Sodium carboxymethyl cellulose 0.2 (8) Bentonite 0.5 (9) Propylene glycol 4.0 (10) Triethanolamine 1. 1 (11) Methyl parahydroxybenzoate 0.1 (12) Pyridoxine hydrochloride 0.1 (13) Sodium dihydrolipoate 0.1 (14) Fragrance 0.1 (15) Purified water 57.7 (16) Titanium oxide 0 (17) Talc 4.0 (18) Bengala 3.0 (19) Yellow iron oxide 2.5 (20) Black iron oxide 0.5 Manufacturing method: After mixing pigments of (16) to (20), pulverizer And pulverize. (15) was heated to 70 ° C., (8) was added to swell well, to which was added (7) previously dispersed in (9), and (10) and (11) were added. Allow to dissolve. (1)-(6)
Are mixed, heated and melted to 80 ° C. The pigment is added to the aqueous phase with stirring and passed through a colloid mill for 7 minutes.
The temperature was adjusted to 5 ° C, the oil phase was added with stirring to emulsify, and after cooling, (12) to (14) were added and mixed at 40 ° C.

Example 12 Cream Foundation (1) Stearic acid 5.00 (% by weight) (2) Lipophilic glyceryl monostearate 2.50 (3) Propylene glycol monolaurate 3.00 (4) Cetostearyl alcohol 1.00 (5) Liquid paraffin 7.00 (6) Isopropyl myristate 8.00 (7) β-carotene 0.10 (8) Astaxanthin 0.05 (9) Sorbitol 3.00 (10) Tri Ethanolamine 1.20 (11) Methyl parahydroxybenzoate 0.15 (12) Sodium lipoate 0.15 (13) Dihydrolipoamide 0.02 (14) Fragrance 0.15 (15) Purified water 47.68 (16 ) Titanium oxide 8.00 (17) Kaolin 5.00 (18) Talc 2.00 (19) Bentonite 1.00 (20) Bengala 2.60 (21) Yellow iron oxide 2.10 (22) Black iron oxide 0 .30 Production method: (16) After mixing the pigments of (22) to (22), the mixture is pulverized by a pulverizer. (9) to (11), (15) are mixed, dissolved and heated. (1) 〜
The oil phase of (8) is mixed, heated and dissolved to 80 ° C. The pigment is added to the aqueous phase with stirring, brought to 75 ° C. through a colloid mill, and the oil phase is added with stirring and emulsified,
After cooling, add (12) to (14) at 40 ° C and mix.

A use test was conducted on Examples 1, 2 and 4 among the above Examples. At that time, Table 1
-About the comparative example 1-the comparative example 6 shown in Table 3, the test was also performed simultaneously. These comparative examples were prepared in the same manner as in Example 1, Example 2 and Example 4, respectively.

[Table 1]

[Table 2]

[Table 3]

(1) Effect of improving skin roughness A group of 20 female panelists having remarkable skin roughness symptoms was allowed to use each of the examples and comparative examples twice a day in a blind continuously for one month. 1 month after observing the skin symptoms,
The comparison was made before the start of use. The skin roughness symptoms were scored according to the criteria shown in Table 4, and the average value of 20 persons was calculated.

[Table 4]

(2) Wrinkle Prevention Effect Five hairless mice were grouped into one group, and the examples and comparative examples of each group were applied once a day to the back once a day, and 1 J / cm ² / week long wavelength ultraviolet (UVA) ) Was irradiated for 50 weeks. The occurrence of wrinkles on the back skin of the hairless mouse was evaluated according to the criteria shown in Table 5, the average value of each group was determined, and the relationship with the number of days of UVA irradiation was determined. A group to which purified water was similarly applied was used as a control.

[Table 5]

(3) Improvement effect of pigmentation symptoms Female paneler 2 having remarkable pigmentation symptoms such as spots and freckles
0 group was used as one group, and each group was used for each month twice a day for one month in Examples and Comparative Examples. The state of pigmentation of the skin after one month was observed and compared with that before use. .
The state of pigmentation was evaluated according to the criteria shown in Table 6,
The average value of 20 persons was calculated.

[Table 6]

Table 7 summarizes the results of use tests on the effects of improving skin roughness and pigmentation symptoms. From Table 7, it can be seen that in the group using the examples of the present invention, rough skin symptoms have been improved to almost healthy skin condition by use for one month,
It also shows that the pigmentation symptoms were significantly improved.
On the other hand, in the comparative example group containing only lipoic acids or antioxidant vitamins, both the rough skin condition and the pigmentation symptom tend to be improved, but the degree is significantly higher than that of the group using the example. It was small.

[Table 7]

Table 8 shows the effect of preventing the occurrence of wrinkles.
The results are shown in FIG. In the group applied with the examples of the present invention, even after irradiation with UVA for 50 weeks, the occurrence of minute wrinkles was recognized, but in the group applied with the comparative example, the occurrence of wrinkles was smaller than in the control. However, in some cases, generation of moderate wrinkles was recognized, and the effect of preventing wrinkles was remarkably small as compared with the group applied with the examples.

[Table 8]

In the examples of the present invention, no change in state was observed even after storage for 3 months, and there was no problem in stability. In addition, in the above use test, no panelists recognized skin irritation or skin sensitization.

[0043]

As described above in detail, the present invention has an excellent elimination effect of reactive oxygen species and improves skin aging symptoms such as rough skin, wrinkles and spots caused by oxidative stress.
An external preparation for skin having prevention and whitening effects, and further having excellent stability and safety was provided.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification number Office reference number FI Technical display location A61K 7/00 A61K 7/00 F K X

Claims (15)

[Claims] 1. One or two of lipoic acid, its salts and derivatives
And seeds above, vitamin A and derivatives thereof, carotenoids, riboflavin and its derivatives, vitamin B _6, their salts and derivatives, cobalamin compounds, vitamin C, salts and derivatives thereof, vitamin E and derivatives thereof, vitamin K, An external preparation for skin containing one or more selected from the group consisting of adenosine and its derivatives, flavonoids and tannins. 2. The method according to claim 1, wherein one or more of lipoic acid derivatives are selected from alkyl esters, alkenyl esters, amides, dihydrolipoic acids and dihydrolipoamides of lipoic acid. External preparation for skin. 3. Vitamin A and derivatives thereof,
Retinol, its ester, retinal, retinoic acid, its ester, 3-dehydroretinol, its ester, 3-dehydroretinal, 3-dehydroretinoic acid,
The external preparation for skin according to claim 1 or 2, wherein one or two types are selected from the ester and a complex of the ester and a water-soluble vitamin or α-hydroxy acid. 4. Carotenoids such as α-carotene,
β-carotene, γ-carotene, lycopene, lutein, violaxanthin, spiriroxanthin, spheroidene,
The external preparation for skin according to any one of claims 1 to 3, wherein one or more types are selected from astaxanthin. 5. The external preparation for skin according to claim 1, wherein one or two kinds of riboflavin derivatives are selected from flavin adenine dinucleotide and flavin mononucleotide. 6. The skin according to claim 1, wherein one or more kinds of vitamin B ₆ and salts thereof are selected from pyridoxine, pyridoxal, pyridoxamine and salts thereof. External preparation. 7. The cobalamin is selected from one or two or more of cyanocobalamin, methylcobalamin, adenosylcobalamin, hydroxocobalamin and aquacobalamin.
2. The external preparation for skin according to item 1. 8. Vitamin C, salts and derivatives thereof,
One or more selected from ascorbic acid, dehydroascorbic acid and salts thereof, ascorbic acid phosphate, phosphatidyl ascorbic acid and salts thereof, and a complex of ascorbic acid, dehydroascorbic acid with tocopherol and astaxanthin The external preparation for skin according to claim 1, wherein: 9. As vitamin E and derivatives thereof,
α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, their acetates,
The nicotinic acid ester and at least one selected from the group consisting of α-tocopherol, β-tocopherol, γ-tocopherol, a complex of δ-tocopherol and α-hydroxy acid, characterized in that they are selected from the group consisting of: Item 9. An external preparation for skin according to item 8. 10. The external preparation for skin according to claim 1, wherein one or more kinds of vitamin K are selected from phylloquinone, menaquinone and menadione. 11. A method for selecting one or more of adenosine derivatives from 5′-methylthioadenosine, adenosine monophosphate, cyclic adenosine monophosphate, adenosine diphosphate and adenosine triphosphate. Do
The external preparation for skin according to claim 1. 12. The method according to claim 1, wherein one or more flavonoids are selected from catechin, epicatechin, eriodictyol, eriodictin, quercetin, hesperidin, hesperitin and rutin. 2. The external preparation for skin according to item 1. 13. The external preparation for skin according to claim 1, wherein one or more tannins are selected from hamameli tannin and tea tannin. 14. One or more of lipoic acid, salts and derivatives thereof, vitamin A and derivatives thereof, carotenoids, riboflavin and derivatives thereof, vitamin B ₆ ,
One or more selected from the group consisting of salts and derivatives thereof, cobalamin, vitamin C, salts and derivatives thereof, vitamin E and derivatives thereof, vitamin K, adenosine and derivatives thereof, flavonoids and tannins The external preparation for skin according to any one of claims 1 to 13, wherein the content of each is 0.01 to 10% by weight. 15. The external preparation for skin according to claim 1, wherein the external preparation for skin is a cosmetic for skin.