JPH10330280A - Promoter for producing collagen, and skin preparation for external use for preventing aging containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a promoter for producing collagen, manifesting sufficient activities for promoting the production of the collagen at a corium fibroblast, and further to prepare a skin preparation for external use capable of inhibiting the generation of wrinkle and the decrease in elasticity, and further excellent in safety and stability. SOLUTION: This promoter for producing collagen contains an extract of one or more kinds of seaweeds selected from Dictyopteris, Sargassum, Dilophus, Ceratodictyon, Asparagopsis, Polysiphonia and Chondria. Further, the skin preparation for external use contains the promoter for producing the collagen.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a collagen production promoter having an effect of promoting collagen production in dermal fibroblasts. It is intended to provide an external preparation for skin which is effective for preventing or ameliorating aging symptoms of the skin, such as reducing skin elasticity, and which can also exhibit an anti-inflammatory action and a wound healing promoting action.

[0002]

2. Description of the Related Art One of the skin aging phenomena is generation of wrinkles and reduction of elasticity. It is considered that such a phenomenon is caused by the progress of collagen cross-linking due to aging and the degradation of collagen by ultraviolet rays or the like. Accordingly, many cosmetics containing collagen and cosmetics containing a collagen production promoting substance have been developed.

[0003] Collagen in the dermis is produced by dermal fibroblasts and degraded by collagenase produced by dermal fibroblasts. Therefore, cosmetics have been proposed in which a collagenase inhibitor that inhibits the activity of collagenase is blended to suppress the decomposition of collagen and to suppress wrinkles and decrease in elasticity.

[0004] However, conventional cosmetics containing collagen have problems in percutaneous absorption and stability, and have not fundamentally improved the amount of collagen in the dermis. In addition, a sufficient anti-aging effect has not been obtained in cosmetics containing a collagen production promoter or a collagenase inhibitor, and more effective anti-aging agents have been desired.

[0005]

DISCLOSURE OF THE INVENTION The present invention relates to a collagen production promoter which exerts a sufficient collagen production promoting effect on dermal fibroblasts, and to contain wrinkles and elasticity by containing the collagen production promoter. It is an object of the present invention to provide an external preparation for skin that suppresses a decrease in skin pressure and is excellent in safety and stability.

[0006]

Accordingly, compounds having an effect of promoting collagen production in dermal fibroblasts were widely searched for from natural products. As a result, Dictyo
pteris), Sargassum (Sargassum), Fukurin'amiji genus (Dilophus), Kaimensou genus (Ceratodictyo
n ), genus Asparagopsis , genus Astragopsis ( Pol )
ysiphonia ) and one or more seaweed extracts selected from the genus Chondria have been found to have a high collagen production promoting effect on fibroblasts. Also,
An external preparation for skin containing this compound suppressed generation of wrinkles and a decrease in elasticity and was found to be excellent in both safety and stability, and completed the present invention.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The seaweed of the genus Dictyopteris used in the present invention is a kind of algae of the family Aphididae of the order Aphididae. Examples of seaweeds of the genus Artemisia include Dictyopteris latiuscula , Dictyopteris undulata and Dictyop .
teris prolifera ), Sujiyahazu ( Dictyopteris plagio )
gramma ), Himeyahazu ( Dictyopteris repens ), Ezoyahazu ( Dictyopteris divaricata ), Urabashiyahazu ( Dictyopteris polypodioides ) and the like. Among these algae genus Algae, from the viewpoint of the collagen production promoting effect, Vladivostalis ( Dictyopteris polypodio)
ides ) is preferably used.

The genus Honda ( Sargas) used in the present invention
The seaweed of sum ) is a kind of algae of the brown algae Hymenoptera, Brassicaceae. Incorporating an extract of Honda straw ( Sargassum fulvellum ) into a whitening cosmetic is disclosed in
4308 and JP-A-2-124810. However, that the seaweed extract of the genus Hondawara has a collagen production promoting action,
It is not known that a skin external preparation containing this extract exerts an antiaging effect.

The seaweeds of the genus Sargassum include, but are not limited to, Sargassum fulvellum , pea ( Sargassum yendoi ), and beetle ( Sargassum pil ).
uriferum), Yatsumatamoku (Sargassum patens), akamoku (Sargassum horneri), Nokogirimoku (Sargassum
serratifolium ), Pterodactylus ( Sargassum gi)
ganteifolium ), Jolemoku ( Sargassum tortile ), Willow moku (Obamoku: Sargassum ringgoldianum ),
Nejimoku ( Sargassum sagamianum ), Hahakimoku ( Sarg
assum kjellmanianum ), Sea turranoo ( Sargassum thu )
nbergii ), fushijimoku ( Sargassum confusum ), isomok ( Sargassum hemiphyllum ), saragus ( Sargass )
um nigrifolium ), sperm ( Sargassum micracanthu )
m ), Tamanashimoku ( Sargassum nipponicum ), Ginseng ( Sargassum vulgare ), Phalaenopsis (Hollyhock: Sargassum duplicatum ), Ezononemoku ( Sargas )
sum yezoense ) and the like. Among these algae of the genus Hondara, from the viewpoint of promoting collagen production, pea ( Sargassum yendoi ) and Ezononemoku ( Sar )
gassum yezoense ) and yam Tamokoku ( Sargassum pa
It is preferable to use one or more extracts selected from tens ).

[0010] The genus Fukurinamiji used in the present invention ( Di
Lophus ) is a kind of algae of the order Amis. As a seaweed of the genus Fukulinamiji,
Fukurinamiji ( Dilophus okamurai , Dilophus margin
ata ) is exemplified.

The sponge ( Cera) used in the present invention
The seaweed of todictyon is a kind of algae of the red algae Ceratodontaceae ( Ceratodictyon spon.)
giosum ).

The Aspergillus ( Aspara) used in the present invention
gopsis ) is a kind of algae of the red alga Papiliocephalaceae, Asparagopsis taxifor
mis ), Kaginori ( Asparagopsis hamifera ) and the like. Among them, it is preferable to use an extract of Asparagopsis taxiformis from the viewpoint of a collagen production promoting action.

The genus Polysiph used in the present invention
onia ) is a type of algae belonging to the red alga Aphididae, Fujimatidae . The seaweed Itogusa genus, Moroitogusa (Polysiphonia morrowii), Shaw Zhou Ke glue (Pol
ysiphonia urceolata), Mutsuitogusa (Polysiphonia
senticulosa), Kiburiitogusa (Polysiphonia japoni
ca ), blackgrass ( Polysiphonia forcipata ), and blackgrass ( Polysiphonia crassa ). Among these seaweeds belonging to the genus Brucella, polysiphonia morrowi ( Polysiphonia morrowi) is considered to have an effect of promoting collagen production.
It is preferred to use the extract of i ).

The genus Salix ( Chondr) used in the present invention
The seaweed of ia ) is a kind of algae of the red alga Aphididae, Pteridophyta. As the seaweeds of the genus Salix, Yuna ( Chondr
ia crassicaulis ), willow laver ( Chondria dasyphyll )
a ), Akauna ( Chondria atropurpurea ), Motsureyuna ( Chondria intricata ), Salix ( Chondria armat )
a ), and Chondria ryukyuensis . Among these seaweeds of the genus Salix, in order to promote collagen production, it is preferable to use the oyster ( Chondria c rassic
aulis ).

Examples of the extraction solvent for obtaining these seaweed extracts include water, alcohols such as ethanol, methanol, isopropanol, isobutanol, n-hexanol, methylamyl alcohol, 2-ethylbutanol and n-octyl alcohol, and glycerin. Or polyhydric alcohols such as ethylene glycol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, propylene glycol, propylene glycol monomethyl ether, propylene glycol monoethyl ether, triethylene glycol, 1,3-butylene glycol, and hexylene glycol Derivatives, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl-n-
One or more mixed solvents selected from polar solvents such as ketones such as propyl ketone, esters such as ethyl acetate and isopropyl acetate, and ethers such as ethyl ether, isopropyl ether and n-butyl ether are preferred. It can be used, and phosphate buffered saline can be used, but is not particularly limited. Alternatively, it is selected from hydrocarbons such as petroleum ether, n-hexane, n-pentane, n-butane, n-octane and cyclohexane, and low-polar solvents such as carbon tetrachloride, chloroform, dichloromethane, trichloroethylene, benzene, and toluene. One or more mixed solvents can also be suitably used.

For the purpose of the present invention, a polar solvent is preferred from the viewpoint of promoting collagen production, and one or more mixed solvents selected from ethanol, methanol, 1,3-butylene glycol and water are preferred. Alternatively, phosphate buffered saline (pH 7.4) is preferable.

As the algae used in the present invention, those collected from water as they are or dried. The site of use is not particularly limited, and the entire algae may be used, or only a part of the algae, such as the body, branches, and roots, may be used.

Further, as an extraction method, a method of extraction by impregnation at room temperature, in a cooled or heated state, a method of extraction using a distillation method such as steam distillation, and a method of compressing raw algae to obtain an extract Examples of the method include squeezing and the like, and these methods are used alone or in combination of two or more.

The ratio of the plant to the solvent at the time of extraction is not particularly limited.
000 weight times, especially 0.5 to 10 in terms of extraction operation and efficiency.
0 times by weight is preferred. The extraction temperature is conveniently in the range from room temperature to the boiling point of the solvent under normal pressure, and the extraction time varies depending on the extraction temperature and the like, but is preferably in the range of 2 hours to 2 weeks.

The seaweed extract thus obtained can be used as it is, or can be subjected to purification operations such as deodorization, decolorization, concentration, etc. within a range not to lose the collagen production promoting action. Furthermore, a fraction may be obtained by column chromatography or the like. These extracts, deodorized products, purified products, and fractionated products can be dried by removing the solvent therefrom, and can be used as a collagen production promoter in a form solubilized in a solvent such as alcohol or an emulsion. Can be provided as

The amount of these collagen production promoters to be added to the external preparation for skin is desirably in the range of 0.001 to 20% by weight in view of the effect and the scent and color tone when added. When the amount is less than 0.001% by weight, a sufficient anti-aging effect cannot be obtained, but the effect of promoting collagen production is so strong that there is no need to add a large amount. It may affect the stability of the agent.

In the present invention, an external preparation for skin can be provided by containing the above-mentioned collagen production promoter, but the external preparation for skin can be in the form of a lotion, emulsion, cream, ointment or the like. Furthermore, flexible lotion,
Lotions such as astringent lotion and lotion for washing, creams such as emollient cream, moisture cream, massage cream, cleansing cream, makeup cream, emollient emulsion, moisture emulsion,
To provide anti-aging cosmetics in various formulations, such as emulsions such as nourishing emulsion and cleansing emulsion, jelly packs, peel-off packs, wash-off packs, packs such as powder packs, serums, and face wash. Can be.

In the present invention, other active ingredients such as other cell activators, whitening ingredients, humectants, anti-inflammatory agents, ultraviolet absorbers, etc. can also be used in combination, and sunscreen cosmetics and skin protection cosmetics can be used. , A cosmeceutical such as a whitening agent or a quasi-drug.

[0024]

EXAMPLES Further, the features of the present invention will be described in detail with reference to examples.

[Examples 1 to 9] Collagen production promoters Collagen production promoters were prepared using the seaweeds and solvents shown in Table 1, and the results are shown in Examples 1 to 9. In the extraction method, the collected seaweed was washed with water, cut into small pieces, dispersed in an equal weight of solvent, stirred with a blender mill, centrifuged, and the supernatant was used as a collagen production promoter. The phosphate buffered saline (pH 7.4) used as the extraction solvent was composed of 8.0 g of sodium chloride, 0.2 g of potassium chloride, 1.15 g of disodium hydrogen phosphate, and 0.25 g of potassium dihydrogen phosphate.
g, calcium chloride 0.1 g, and magnesium chloride hexahydrate 0.1 g were dissolved in distilled water to make 1000 ml.

[0026]

[Table 1]

The collagen production promoting effect of the collagen production promoter of the present invention was examined using cultured human dermal fibroblasts. Human dermal fibroblasts are cultured in Dulbecco's minimum essential medium supplemented with fetal calf serum, and after 24 hours, the medium is replaced with the above-mentioned medium supplemented with the collagen production promoter shown in Examples 1 to 13 and cultured for 7 days Continued.
Procollagen in the culture supernatant can be converted to a commercial kit (Takara
It was quantified by enzyme immunoassay (ELISA) using Procollagen Type IC-Peptide EIA Kit). At that time, the culture was performed without adding a collagen production promoter as a control, and the procollagen production rate (%) was calculated, assuming that the amount of procollagen production in the control was 100%. Procollagen is a precursor of collagen, and procollagen is converted into collagen after being secreted from the cells.

[0028]

[Table 2]

Table 2 shows the relationship between the concentration of the collagen production promoter and the collagen production rate. As is clear from Table 2, by adding the collagen production promoter of the present invention and culturing fibroblasts, a significant increase in collagen production was observed. In particular, Example 1 containing the extract of Urabashiyahazu, Example 3 containing the extract of Ezononejimoku, Example 5 containing the extract of fukurinamiji.
When each of the collagen production promoters of Example 6 and Example 8 containing the sponge extract was added, a significant collagen production promoting effect was obtained at a low concentration of 0.3% by volume or less. I was No cytotoxicity to fibroblasts was observed in the concentration range in which this experiment was performed.

Examples 10 to 18 Oil-in-water emulsified creams Oil-in-water emulsified creams containing the collagen production promoters shown in Table 3 were prepared. (1) Beeswax 6.0 (% by weight) (2) Cetyl alcohol 5.0 (3) Hydrogenated lanolin 8.0 (4) Squalane 37.5 (5) Monoglyceryl stearate 4.0 (6) Sesquiolein Sorbitan acid 2.0 (7) Polyoxyethylene (50EO) hydrogenated castor oil 2.0 (8) Glycerin 5.0 (9) Methyl parahydroxybenzoate 0.2 (10) Purified water 28.3 (11) Collagen production Accelerator 2.0 Production method: After each of the oil phase (1) to (7) and the aqueous phase component (8) to (10) are heated to 75 ° C. and homogenized, the aqueous phase is gradually added to the oil phase. The mixture is added with stirring, and phase inversion is emulsified. The mixture is cooled to 40 ° C. while stirring, and the component (11) is added.

[0031]

[Table 3]

Using the above Examples 10 to 18, the effect of preventing wrinkles caused by ultraviolet rays was evaluated. In addition, Comparative Example 1 was obtained by replacing the collagen production promoter with purified water. The wrinkle prevention effect is achieved by the hairless mouse 5
The animals were divided into groups, and the examples and comparative examples of each group were applied to the back once a day, respectively, and irradiated with 1 J / cm ² / week long-wave ultraviolet light (UVA) for 50 weeks, and the occurrence of wrinkles in hairless mice The situation was observed and scored according to the criteria shown in Table 4. At this time, a group to which only purified water was applied was used as a control. As a result, the average value of each group was calculated, and UVA
Table 5 shows the relationship with the number of irradiation days.

[0033]

[Table 4]

[0034]

[Table 5]

As shown in Table 5, in the control group, the depth of the formed wrinkles reached a medium level when the number of UVA irradiation days exceeded 40 weeks, and deep wrinkles occurred after 50 weeks. It was allowed. On the other hand, in each of the groups to which the examples of the present invention were applied, the occurrence of wrinkles was remarkably suppressed to the extent that slight or slight wrinkles were observed after 50 weeks in each case. On the other hand, no significant suppression or reduction of wrinkles was observed in the group to which the comparative example was applied.

Subsequently, Examples 10 to 18 of the present invention
And about Comparative Example 1, the anti-inflammatory effect and the effect of promoting wound healing were evaluated. Group 5 with artificial inflammation or wound formation
Using mice, 0.5 g of each of Examples and Comparative Examples was applied to each group twice a day for 7 days, and on the 7th day, the state of the inflamed site and the wound site was observed. The anti-inflammatory effect was evaluated in three stages: "effective", "slightly effective", "ineffective", and the effect of promoting wound healing in three stages: "complete healing", "almost healing", and "incomplete healing". Table 6 shows the number of obtained mice.

[0037]

[Table 6]

As is clear from Table 6, no anti-inflammatory effect was observed in any of the mice in the group to which the present invention was applied, and no anti-inflammatory effect was effective in three or more mice. Was recognized. Regarding the effect of promoting wound healing, none of the mice to which the wound healing was incomplete was observed in the group to which the examples of the present invention were applied, and complete healing was observed in two or more mice. On the other hand, in the group to which Comparative Example 1 was applied, one mouse in which a slightly effective anti-inflammatory effect was observed was found, but in the remaining four cases, no anti-inflammatory effect was observed at all. Further, in all the applied groups of Comparative Example 1, wound healing was incomplete.

Next, a six-month actual use test was conducted on Examples 10 to 18 and Comparative Example 1 of the present invention. As panelists, women in their 40s to 60s who had skin symptoms such as reduced skin elasticity were used, and 20 women were included in each group. The use test was performed by using each of the examples or the comparative examples with a blind in each group. Before the start of the use test and after the end of the use test, the elasticity of the skin was measured with a cute meter, and the improvement state of the skin elasticity before and after the use was evaluated in three stages of “improvement”, “slight improvement”, and “no change”. The results are shown in Table 7 by the number of panelists who obtained each evaluation.

[0040]

[Table 7]

As shown in Table 7, in the group using the examples of the present invention, improvement in skin elasticity was observed in all panelists. In particular, 80% was used in the groups using Examples 10, 12, 14, 15, and 17.
The above panelists have clearly seen improvement. In contrast, in the group using Comparative Example 1, none of the panelists recognized a clear improvement in skin elasticity, and 65% of the panelers did not improve the symptoms.

In Examples 10 to 18 of the present invention, during the above-mentioned use test period, the precipitation of the contained components,
No state changes such as separation, aggregation, discoloration, and odor were observed. In addition, in each group used in Examples, there was no paneler showing a skin irritating reaction or a skin sensitizing reaction.

Next, the formulation of another embodiment of the present invention will be described. [Example 19] Lotion (1) Ethanol 10.0 (wt%) (2) Methyl paraaminobenzoate 0.2 (3) Glycerin 10.0 (4) Collagen production promoter (Example 1) 5.0 (Example 1) 5) Purified water 74.8 Production method: After dissolving (2) in (1), the components (3) to (5) are sequentially added, and the mixture is dissolved and homogenized.

Example 20 Oil-in-Water Emulsion (1) Beeswax 0.5 (% by weight) (2) Vaseline 2.0 (3) Squalane 5.0 (4) Sorbitan sesquioleate 0.8 (5) Sucrose fatty acid ester 1.2 (6) Propylene glycol 5.0 (7) Purified water 57.4 (8) Sodium carboxymethyl cellulose 20.0 (1% by weight aqueous solution) (9) Ethanol 5.0 (10 ) Methyl paraoxybenzoate 0.1 (11) Collagen production promoter (Example 2) 3.0 Production method: 75 parts each of the oil phase components (1) to (4) and the aqueous phase components (5) to (7) After the mixture was homogenized by heating to 70 ° C., the oil phase was added to the aqueous phase and pre-emulsified while stirring. Further, after the component (8) heated to 70 ° C. was added, the mixture was emulsified with a homomixer.
The mixture is cooled to 40 ° C. while stirring, and the components (9) to (11) are mixed and added uniformly.

Example 21 Water-in-oil emulsion (1) Beeswax 2.0 (% by weight) (2) Microcrystalline wax 1.0 (3) Lanolin 2.0 (4) Liquid paraffin 30.0 (5) ) Aluminum stearate 0.2 (6) Sorbitan sesquioleate 4.0 (7) Sucrose fatty acid ester 1.0 (8) Glycerin 8.0 (9) Collagen production promoter (Example 3) 3.0 ( 10) Methyl paraoxybenzoate 0.3 (11) Purified water 48.5 Production method: The oil phase components (1) to (6) and the aqueous phase components (7) to (11) are each heated to 75 ° C and mixed uniformly. After emulsification, the aqueous phase is added to the oil phase, emulsified, and then cooled.

[Example 22] Water-in-oil ointment (1) Beeswax 3.0 (wt%) (2) Hydrogenated lanolin 8.0 (3) Squalane 34.0 (4) Solid paraffin 2.0 (5) ) Microcrystalline wax 9.0 (6) White petrolatum 5.0 (7) Hexyldecyl adipate 10.0 (8) Sorbitan sesquioleate 3.5 (9) Polyoxyethylene (50EO) hydrogenated castor oil 1.0 (10) Propylene glycol 2.0 (11) Collagen production promoter (Example 4) 1.0 (12) Purified water 21.5 Production method: Oil phase of (1) to (9) and (10) to (12) After heating each of the aqueous phase components of (1) to 75 ° C. to homogenize the mixture, the aqueous phase is added to the oil phase and emulsified. Cool to 40 ° C. with stirring.

[Example 23] Oil-based cleansing cream (1) Ceresin 8.0 (wt%) (2) Microcrystalline wax 5.0 (3) White petrolatum 35.0 (4) Squalane 49.5 (5) Collagen Production enhancer (Example 5) 0.5 (6) Magnesium stearate 2.0 Production method: Components (1) to (6) are mixed and heated to gel,
Cooling.

[Example 24] Emulsion foundation (1) Stearic acid 2.4 (wt%) (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 carboxymethylcellulose 0.2 (8) Bentonite 0.5 (9) Propylene glycol 4.0 (10) Triethanolamine 1. 1 (11) Purified water 55.5 (12) Collagen production promoter (Example 6) 2.5 (13) Fragrance 0.1 (14) Titanium oxide 8.0 (15) Talc 4.0 (16) Bengala 3.0 (17) Yellow iron oxide 2.5 (18) Black iron oxide 0.5 Production method: After mixing the pigments of (14) to (18), the mixture is pulverized by a pulverizer. (11) is heated to 70 ° C., and (8) is added to swell well. To this is added (7) previously dispersed in (9), and then (10) is added and dissolved. The oil phases (1) to (6) are mixed, heated and melted to 80 ° C. The pigment is added to the aqueous phase with stirring, the mixture is heated to 75 ° C. through a colloid mill, and the oil phase is added with stirring to emulsify.
Add (12) and (13) at ° C.

Example 25 Hair Cream (1) Polyoxyethylene (10EO) behenyl ether 5.0 (% by weight) (2) Hexyldecanol 5.0 (3) Liquid paraffin 35.0 (4) Purified lanolin 2 5.0 (5) Cetanol 2.0 (6) Glycerin 5.0 (7) Collagen production promoter (Example 8) 5.0 (8) Purified water 40.9 (9) Fragrance 0.1 Production method: (1) ) To (5) are mixed and heated to 75 ° C. On the other hand, the aqueous phase components (6) to (8)
The temperature was adjusted to 5 ° C., and the oil phase was added to the mixture and emulsified.
At 0 ° C. add (9).

[0050]

As described in detail above, the genus Dictyopteris , the genus Sargassum , the genus Dilophus , and the genus Ceratodi
Ctyon), Kagikenori genus (Asparagopsis), Itogusa genus (Polysiphonia), 1 or more types of collagen production promoting agent comprising an extract of seaweed selected from Yanaginori genus (Chondria) is a high collagen production promoting effect An external preparation for skin containing this collagen production promoter is effective for preventing or improving skin aging symptoms such as generation of wrinkles and a decrease in elasticity of the skin, and also has an anti-inflammatory action and a wound healing promotion action. In addition, safety and stability are good.

Continuing from the front page (72) Inventor Tomomi Arashima 112-1 Nogami, Okada-cho, Yokaichi-shi, Shiga Co., Ltd. Inside Noevir Shiga Central Research Laboratory (72) Inventor Kunihiko Masuda 112-1 Nogami, Okada-cho, Yokaichi-shi, Shiga Co., Ltd. Noevir Shiga Central Research Laboratory Co., Ltd.

Claims (3)

[Claims] 1. The genus Dictyopteris , the genus Sargassum , and the genus Dilophu
s), Kaimensou genus (Ceratodictyon), Kagikenori genus (Asparagopsis), Itogusa genus (Polysiphonia), collagen characterized by containing one or two or more of seaweed extract is selected from Yanaginori genus (Chondria) Production promoter. 2. An external preparation for skin, comprising the collagen production promoter according to claim 1. 3. The external preparation for skin according to claim 2, wherein the external preparation for skin is a cosmetic for preventing aging.