JP2001288113A - Skin care composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin care composition capable of exhibiting excellent actions on the prophylaxis and amelioration of skin aging such as the formation of the dry skin and wrinkles, or a reduction of dermatoglyphics. SOLUTION: This skin care composition is characterized as comprising an expression promoter of desmoglein, desmocollin or desmoplakin which is a demosome constituent protein and/or an expression inhibitor of loricrin or involucrin which is a keratin envelope precursor protein as an active ingredient.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a composition for external use on the skin which is effective for preventing and improving skin aging such as formation of rough skin and wrinkles and reduction of texture.

[0002]

2. Description of the Related Art In general, changes in skin surface morphology with age include wrinkle formation, reduction of texture, and rough skin. Although the mechanisms of these pathogenesis are not fully understood and there are many unclear points, in general, decreased epidermal cell proliferation ability, decreased energy metabolic activity, decreased turnover speed, abnormal keratinization, stratification of the stratum corneum, Caused by flattening of the papillary layer,
A decrease in the water content of the stratum corneum, abnormal peeling of the stratum corneum due to drying, and a change in the physical properties of the stratum corneum (decrease in flexibility and elasticity) occur. Clarification, non-uniform changes, and the formation of fine lines are observed.

[0003] For the purpose of preventing or improving such changes in skin surface morphology, humectants have hitherto been known, and for example, urea, glycerol, amino acid derivatives, mucopolysaccharides, various natural products and the like are used as active ingredients. Attempts have been made to use cosmetics. (Toshimura Takemura, Pharmacia, 28, 1,199
2).

[0004] However, these active ingredients have a weak action, and it is difficult to exert a sufficient effect even in a small amount, and they are also insufficient in terms of sustainability, stability, and feeling upon use. In addition, vitamin A as a highly effective active ingredient
Acids and α-hydroxy acids are known (Journal of the Japan Cosmetic Science, 16, 3, 172-174, 1992), but these have problems in skin irritation and stability.

[0005] On the other hand, desmosomes are adhesive structures that stop between epidermal cells. Adhesion between epidermal cells via desmosomes cooperates with a cytoskeleton composed of keratin fibers.
It is known that a strong structure in epithelial tissue is maintained (Standard Dermatology 5th Edition, Chapter 17, Medical Shoin, 1997). Desmosome constituent proteins are known as desmogleins I, II, III, desmocholine I, II, III, desmoplakin I, II, etc., and any structure or binding ability of these constituent proteins is impaired.
The epidermal cytoskeletal network collapses and the epidermis leads to bullous disease (Yasuo Kitajima, Clinical Immunity 30, suppl. 18, 199)
8). Thus, although the function of desmosomes in the skin and diseases caused by abnormal adhesion were known, the expression of desmosome constituent proteins decreased with the aging of the skin,
The formation of wrinkles, the reduction of texture, and the roughness of the skin resulting therefrom are not known, and a skin external preparation composition containing an expression promoter for desmosome-constituting proteins has not yet been known.

[0006] On the other hand, the stratum corneum envelope is also called a peripheral zone or a marginal zone, and is a very strong insoluble giant protein that lines the cell membrane of keratinocytes. Precursor proteins of this stratum corneum envelope include loriculin, involucrin, elafin, cystatin A, etc., which are crosslinked by transglutaminase 1 to become a stratum corneum envelope (Standard Dermatology 5th Edition, Chapter 17, Medical Shoin 1997 ). Furthermore, with regard to dysfunction in the skin, it is known that in ichthyosis, precursor protein cross-linking deficiency, decreased expression level in psoriasis, and changes in the cell layer expressed in wound healing and psoriasis (Nisshin Gakkai: 110 (1) ), 2000). However, the increase in the expression of the stratum corneum precursor protein associated with skin aging, and the resulting wrinkle formation, reduced texture, and rough skin are not known.
Further, a skin external preparation composition containing an inhibitor of the expression of a stratum corneum envelope precursor protein has not yet been known.

[0007]

SUMMARY OF THE INVENTION The present invention is intended to solve the problems and the current state of the prior art described above. A small amount of the present invention can provide a sufficient effect, and at the same time, can provide sustainability, stability and usability. It is an object of the present invention to provide a composition for external use on the skin which has excellent effects and the like, and is suitable for safely improving rough skin and preventing and improving skin aging.

[0008]

Means for Solving the Problems In view of the above-mentioned conventional problems, the present inventors have conducted intensive studies on the mechanism of rough skin and skin aging. As a result, skin aging, ie, wrinkle formation and texture reduction, have been observed in epidermal cells. It has been found that the decrease in the amount of cell adhesion factor desmosome and the increase in the amount of stratum corneum envelope are greatly involved, and that the substance that promotes the expression of desmosome component proteins and the substance that suppresses the expression of stratum corneum precursor protein is used for rough skin and skin. The present inventors have found that skin problems associated with aging can be prevented and improved, and have completed the present invention. That is, the present invention resides in the following (1) and (2). (1) An external preparation for skin comprising a desmosome constituent protein, desmoglein, desmocholine, a desmoplakin expression promoting substance and / or a corneal envelope precursor protein, loriculin and an involucrin expression suppressing substance. . (2) The substance according to (1) is geranylgeranylacetone,
An external composition for skin containing at least one selected from indole alkaloids and bryostatin as an active ingredient.

[0009]

Embodiments of the present invention will be described below in detail. The composition for external application to the skin of the present invention is a desmosome, a desmosome constituent protein, which is a cell adhesion factor desmosome constituent protein of epidermal cells, and a substance for promoting expression of desmoplakin and / or a stratum corneum envelope precursor protein.
It is characterized by containing a substance inhibiting the expression of loriculin and involucrin.

As the substance for promoting the expression of desmoglein used in the present invention, a substance having a cell differentiation-inducing action is preferable. For example, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol and its substances 2-acylaminopropanol derivatives (for example, salts (pharmaceutically acceptable salts), the same applies hereinafter) (JP-A-9-169664)
), Quinone derivatives such as menatetrenone (vitamin K ₂ ) (JP-A-6-305595), and benzoic acid derivatives such as acetaminophenic acid (JP-A-7-2067).
No. 65), glycolipids (JP-A No. 7-258100), 24-hydroxycholecalciferol, 26,
27- dimethyl -22-1Arufa, 25-hydroxycholecalciferol, 1.alpha.-hydroxy cholecalciferol, calcivirus poly triol, l [alpha], 25-activated vitamin D ₃ such as hydroxy cholecalciferol (JP-A 6-179622 JP ), Bufalin (Cancer Re
s., 52-2,4634-4641,1992), f sediment xanthine (JP-A-9-151132), coenzyme A [C ₂₁ H ₃₆
N ₇ O ₁₆ P ₃ S, “CoA”] and oxidized CoA obtained by oxidizing the salt thereof and / or a salt thereof (Japanese Patent Laid-Open No. 2-49729), and a seaweed extract, Durvilleaceae
Extract (JP-A-9-268119), geranylgeranylacetone (JP-A-6-192073), which has been conventionally used as a therapeutic agent for inducing cell differentiation, anticancer and gastritis, and conventionally used as a differentiation-inducing activity / anticancer agent Indole alkaloids (JP-A-8-283239)
Bulletin), obtained from the extraction angle of the marine bryozoan, has a microlide structure, and is an antitumor agent (J. Amer. C
hem. Soc, 104, 6846, 1982), and bryostatin (J. Amer. Chem. Soc, 104, 6846, 1982), and the like.

As the substance for promoting the expression of desmocholine used in the present invention, a substance having a cell differentiation inducing action is preferable. For example, methylphenylacetamide, ethylphenylacetamide, phenylacetic acid ethyl ester, 2,4-dichlorophenylacetic acid, Indole acetic acid (the above-mentioned JP-A-8-245376),
Acylpropanol derivatives (JP-A-9-169664) and the above-mentioned benzoic acid derivatives (JP-A-7-20676)
No. 5), the glycolipid described above (JP-A-7-258100)
JP), above the active vitamin D ₃ compounds (JP-A-6-
179622), the above-mentioned oxidized CoA and / or a salt thereof (JP-A-2-49729), the above-mentioned Durvilleaceae extract, the above-mentioned geranylgeranylacetone (JP-A-6-192073),
The above-mentioned indole alkaloids (JP-A-8-2832)
No. 39), bryostatin described above (J. Amer. Chem.
Soc, 104, 6846, 1982).

As the substance for promoting the expression of desmoplakin used in the present invention, a substance having a cell differentiation-inducing action is preferable. For example, 1,9-nonanedicarboxylic acid,
Mono- or dicarboxylic acids such as 1,8-octanedicarboxylic acid, 1,10-decanedicarboxylic acid, 1,7-heptanedicarboxylic acid (JP-A-6-321779), and 1,3-dioxolebenzene derivatives Kaihei 9
JP-A-194369), the above-mentioned 2-acylpropanol derivative (JP-A-9-169664), the above-mentioned quinone derivative (JP-A-6-305595), and the above-mentioned benzoic acid derivative (JP-A-7-206765). ), the above-mentioned glycolipids (JP-a-7-258100), the above-mentioned active vitamin D ₃ compounds (JP-a-6-17
No. 9622), vitamin K, calophilis extract,
Bodaiju extract, glycolic acid, oxidized Co as described above
A and / or a salt thereof (JP-A-2-49729);
The above-mentioned Durvilleaceae extract, the above-mentioned geranylgeranylacetone (JP-A-6-192073)
JP), the above-mentioned indole alkaloids (Japanese Unexamined Patent Application Publication No.
283239), the above-mentioned bryostatin (J.
Amer. Chem. Soc, 104, 6846, 1982). The plant extract may be an extract extract or a product separated and purified from the extract. In the case of extract,
The above plant can be obtained by solvent extraction of a dried or crushed plant, and if the extraction solvent is non-toxic for use, the extract can be used as it is, as a diluent diluted with an appropriate solvent. It may be used, or a concentrated extract, a dry powder by freeze-drying or the like, or a paste-like preparation may be used.
As the solvent used to obtain the plant extract, methanol, ethanol, butanol, hexane, heptane, cyclohexane, ethyl acetate, commonly used organic solvents such as acetone, and water and the like can be mentioned. Can be used alone or in combination of two or more. Among these solvents, polar solvents are preferred, and ethanol and water are more preferred. In addition, the extraction treatment can be performed by a conventional method at a temperature of usually about 3 to 70 ° C. In addition to the solvent extraction, an extract obtained by supercritical extraction in which carbon dioxide is brought into a supercritical state can be similarly used. In this case, hexane, ethanol, or the like can be used as an extraction solvent. Furthermore, the separation and purification of the active ingredient from the extract can be performed by purifying the extract by column chromatography, liquid chromatography and the like.

[0013] The production of loricrin used in the present invention is also described.
Has a cell differentiation-inducing effect
Substances are preferred, for example benzamide derivatives, anili
Derivatives (above, JP-A-10-152462),
1,2-benzoquinone, 1,4-benzoquinone, methyl
Parabenzoquinone, 2,6-dimethoxyparabenzoquino
And benzoquinone derivatives such as dimexibenzoquinone
(JP-A-11-228376), tocopherol
(JP-A-6-256181), Octopirox
(JP-A-9-48708), 2-acyl mentioned above
Propanol derivative (Japanese Unexamined Patent Publication No. 9-169664)
Report), the above-mentioned quinone derivatives (Japanese Unexamined Patent Publication (Kokai) No. 6-305595)
), The above-mentioned benzoic acid derivatives (JP-A-7-2067)
No. 65), the glycolipid described above (JP-A-7-25810)
No. 0), the above-mentioned active vitamin D _Three(Japanese Unexamined Patent Publication
179622), the above-mentioned oxidized CoA and / or
Or a salt thereof (JP-A-2-49729);
Geranylgeranylacetone (JP-A-6-192073)
Gazette), the above-mentioned indole alkaloids (Japanese Unexamined Patent Publication No.
283239), the above-mentioned bryostatin (J. Am
er. Chem. Soc, 104, 6846, 1982).

As the substance for suppressing the expression of involucrin used in the present invention, a substance having a cell differentiation inducing action is preferable.
No. 83078), arbstatin (Umezawa, H., et.
al, J. Antibiotics, 39, 170-173, 1986), genistin (Og
awara, H., et.al, J. Antibiotics, 39, 606-608, 1986), lavendastin (onoda, T., et.al, J. Nat. Prod., 52, 1252-1)
257, 1989), the above-mentioned 2-acylpropanol derivative (JP-A-9-169664), the above-mentioned quinone derivative (JP-A-6-305595), and the above-mentioned benzoic acid derivative (JP-A-7-206765). , above glycolipids (JP-a-7-258100), the above-mentioned active vitamin D ₃ compounds (JP-a-6-179622 discloses), above tocopherol (JP-a 6-25618
No. 1), the above-described octopirox (JP-A-9-4)
8708), the above-mentioned oxidized CoA and / or a salt thereof (Japanese Patent Application Laid-Open No. 2-49729), the above-mentioned geranylgeranylacetone (Japanese Patent Application Laid-Open No. 6-192073), and the above-mentioned indole alkaloid (Japanese Patent Application Laid-Open No. 8-2).
No. 83239), the above-mentioned bryostatin (J. Ame
r. Chem. Soc, 104, 6846, 1982). In addition,
Each of the specific examples of the desmoglein, desmocholine, desmoplakin expression promoting substance, and loricrin, each specific example of the involucrin expression suppressing substance are described with reference to each publication and literature, but are disclosed in each publication and literature. The contents (particularly, the details of each specific example disclosed in each publication and literature) are included in the description of this specification.

Although the above-mentioned substances having cell differentiation inducing action have been exemplified, geranylgeranylacetone, indole alkaloids and bryostatin are particularly preferred. These geranylgeranylacetone, indole alkaloid, bryostatin, and each of the above-mentioned desmoglein, desmocholine, desmoplakin expression promoting substances and loriculin, involucrin expression suppressing substances, have an effect on epidermal cells and improve wrinkles based on them. The effects of pattern recovery and skin roughness improvement have not been known at all, and their attributes have been found for the first time by the present inventors. Each of these substances has an excellent effect on both the promotion of the expression of desmosome constituent proteins, desmoglein, desmocholine, and desmoplakin, and the effect of suppressing the expression of loricrin and involucrin, the horny layer envelope precursor proteins. In the present invention, the above-mentioned expression promoter for the desmosome-constituting protein, or the above-mentioned precursor protein for the stratum corneum envelope is used alone or in combination with a substance that is simultaneously effective for both or a combination of a plurality of these substances. Good, that is, it may be used alone or in a combination of two or more, and there is no particular limitation. In addition, the above-described respective substances exemplified in the present invention may be synthesized, or a commercially available substance may be purchased and used.

In the composition for external use on skin of the present invention, the amount of each of the above substances is 0.000001 to 30% based on the total amount of the composition.
% (% Is “% by mass”, the same applies hereinafter), and preferably
It is 0.001-1%. If the amount is less than 0.000001%, the effects of the present invention cannot be achieved, and if the amount exceeds 30%, the effects of the present invention are not enhanced and it is uneconomical.

The skin external preparation composition of the present invention may contain, in addition to the above essential components, various components which are generally used in the skin external preparation composition, if necessary, as long as the effects of the present invention are not impaired. , For example, oils, water, humectants including surfactants,
Alcohol, thickener, antioxidant, sequestering agent,
pH adjusters, preservatives, fragrances, pigments, ultraviolet absorbers, ultraviolet scattering agents, vitamins, amino acids, etc., as well as ellagic acid, ascorbic acid, smectite, trimethylglycine, arbutin, isoflavone, catechin, and oil-soluble licorice, Plant extracts such as coleus, mugwort, aloe, calyx, hypericum, birch, mulberry, peonies and the like can be blended.

The composition for external use on skin of the present invention thus constituted comprises one or both of a substance for promoting the expression of epidermal proteins desmoglein, desmocholine, desmoplakin, and a substance for suppressing the expression of loriculin and involucrin. By containing the composition, it becomes a composition exhibiting effects on skin aging, that is, formation of wrinkles, reduction of texture, and rough skin. The composition for external use on the skin of the present invention has a wide range of bases such as aqueous solutions, solubilizing systems, emulsifying systems, powder dispersion systems, water-oil two-layer systems, water-oil-powder three-layer systems, and the like. It can also be used for creams, milky lotions, lotions, serums, basic cosmetics such as packs,
It can be widely and suitably used in various forms, such as makeup cosmetics such as lipsticks and foundations, pharmaceuticals such as jellies and ointments, and quasi-drugs.

[0019]

Next, the present invention will be described in more detail with reference to Test Examples and Examples, but the present invention is not limited to the following Examples.

[Test Example 1: Test for Promoting Expression of Desmoglein in Human Epidermal Keratinocytes] The active ingredient of the composition for external use of the skin of the present invention promotes the expression of desmoglein (desmosome constituent protein) in normal human epidermal keratinocytes. The following tests were performed to prove that the method had an effect. Normal human epidermal keratinocytes (manufactured by Kurabo Industries) were seeded on a 48-well collagen-coated plate (manufactured by Sumitomo Bakelite) and cultured at 37 ° C. in a 5% carbon dioxide atmosphere for 3 days. After cultivation, the culture supernatant was aspirated and the calcium concentration was adjusted to 1.6 mM. To the medium, no medium (control) and the medium to which the above-mentioned active ingredient was added at 0.01% were added to each well, followed by further culturing for 2 days. . After completion of the culture, the expression of desmoglein was quantified by ELISA using an anti-desmoglein antibody (enzyme immunoassay, the same applies hereinafter). The results of calculating the expression level when the control was set to 1.00 are shown in Table 1 below. In addition,
The higher the numerical value of the expression amount (relative value), the higher the effect of promoting desmoglein expression.

[0021]

[Table 1]

As is evident from the results shown in Table 1, it was found that 13 components from geranylgeranylacetone to bufalin, which are effective components of the external preparation for skin of the present invention, promote desmoglein expression. In particular, for indole alkaloids, 2.0
A high effect of twice or more (2.27) was observed.

[Test Example 2: Desmocholine expression promotion test on human epidermal keratinocytes] Based on Test Example 1, the amount of desmocholine expression was determined. Table 2 below shows the results of calculating the expression level when the control was set to 1.00. The higher the expression level (relative value), the higher the effect of promoting desmocholine expression.

[0024]

[Table 2]

As is evident from the results shown in Table 2, it was found that 13 components from geranylgeranylacetone to bufalin, which are effective components of the composition for external application to the skin of the present invention, promote desmocholine expression. In particular, indole alkaloids showed a high effect of 1.5 times or more (1.87) as compared to the control.

[Test Example 3: Desmoplakin expression promotion test on human epidermal keratinocytes] The amount of desmoplakin expression was determined based on Test Example 1 described above. 1.00 control
Table 3 below shows the results of calculation of the expression level when the expression was used. The higher the expression level (relative value), the higher the effect of promoting desmoplakin expression.

[0027]

[Table 3]

As shown in Table 3 above, it was found that 17 components from geranylgeranylacetone to oxidized CoA, which are effective components of the external preparation for skin of the present invention, promote desmoplakin expression. In particular, bryostatin is 2.5 times or more (2.58) as compared with the control.
High effect was recognized.

[Test Example 4: Test for inhibiting the expression of loricrin on human epidermal keratinocytes] The active ingredient of the composition for external use of the skin of the present invention was used to inhibit the expression of loriculin (corneal envelope precursor protein) in normal human epidermal keratinocytes. The following tests were performed to prove the effect. Normal human epidermal keratinocytes (manufactured by Kurabo Industries) were seeded on a 48-well collagen-coated plate (manufactured by Sumitomo Bakelite) and cultured at 37 ° C. in a 5% carbon dioxide atmosphere for 3 days. After the culturing, the culture supernatant was removed by suction, and a medium with a calcium concentration of 2.0 mM was not added (control) or 0.01% of the above active ingredient was added to each well, followed by further culturing for 2 days. After completion of the culture, the expression level of loriculin was quantified by an ELISA method using an anti-loriculin antibody. The results of calculating the expression level when the control was set to 1.00 are shown in Table 4 below. In addition,
The lower the value of the expression amount (relative value), the higher the effect of suppressing the expression of loricrin.

[0030]

[Table 4]

As is clear from the results shown in Table 4 above, it was found that 14 components from geranylgeranylacetone to 22-oxacalcitriol, which are effective components of the composition for external application to the skin of the present invention, suppressed the expression of loriculin. did. In particular, in the case of geranylgeranylacetone, which is an isoprene derivative, コ ン ト ロ ー ル or less (0.6
The high effect of 4) was recognized.

Test Example 5: Involucrin Expression Inhibition Test on Human Epidermal Keratinocytes Based on the above Test Example 4, the amount of involucrin expression was quantified. 1.00 control
Table 5 below shows the results of calculation of the expression level when the expression was used. The lower the expression level (relative value), the higher the effect of suppressing involucrin expression.

[0033]

[Table 5]

As is clear from the results shown in Table 5 above, it was found that 14 components from geranylgeranylacetone to oxidized CoA, which are effective components of the external preparation for skin of the present invention, suppressed the expression of involucrin. In particular, for the isoprene derivative geranylgeranylacetone,
A high effect of 1/2 or less (0.48) with respect to the control was observed.

[Test Example 6: Skin photoaging test] One group of 5 hairless mice (hos: HR-1, 9 to 10 weeks old, female) was exposed to ultraviolet light (UV-B) 50 mJ once a day on the back skin. / Day · cm ² for 10 weeks, then 1% dissolved in solvent (50% propylene glycol, 25% ethanol, 25% purified water)
Was uniformly applied, and the test solution was applied 5 days a week for 5 weeks. At the time of ultraviolet irradiation, the test substance remaining on the skin was thoroughly wiped with a 30% ethanol solution before irradiation. The evaluation was performed immediately after the end of the irradiation period and immediately after the end of the application test period, and the wrinkle improvement and skin roughness improvement effects were judged visually and compared with the control group of each index. When the recovery of the change in appearance was hardly recognized, the evaluation was x, the improvement was slight, the improvement was ●, and the improvement was marked as ◎. These results are shown in Tables 6 and 7 below. In addition, to determine the texture restoration effect, the back replica was sampled, and the number of texture intersections per unit area was determined, with the point where three or more skin folds meet as one intersection, and compared with the control group. The results are shown in Table 8 below.

[0036]

[Table 6]

[0037]

[Table 7]

As is clear from the results shown in Tables 6 and 7, the 13 components from geranylgeranylacetone to oxidized CoA, which are effective components of the composition for external application to the skin of the present invention, have rough skin and wrinkles due to photoaging. It has been found to be effective in preventing and improving the disease. In particular, geranylgeranylacetone, bryostatin, and indole alkaloid were found to be highly effective in preventing and improving rough skin and wrinkle formation due to photoaging.

[0039]

[Table 8]

As is evident from the results shown in Table 8, 13 components from geranylgeranylacetone to oxidized CoA, which are the effective components of the composition for external application to the skin of the present invention, are effective in restoring the reduction in texture by photoaging. Turned out to be. In particular, geranylgeranylacetone showed a high effect on the control.

[Examples 1 to 19] The formulation examples (cream, hand cream,
Emulsion, lotion, acne remedy, each cream composition,
The total amounts are 100% by mass, respectively) are shown in Tables 9 to 14 below.
Examples 1 to 19 having the composition shown in Tables 9 to 14 below
All showed excellent effects such as an effect of improving rough skin, an effect of improving wrinkles, an effect of improving texture, and a beautiful skin effect (smoothness, moist feeling, tension, gloss, etc.), and also showed good safety.

Examples 1 to 4 The oil layer components and the aqueous layer components shown in Table 9 below were separately heated at 70 ° C., and then mixed and emulsified. While cooling, a fragrance was added on the way and further cooled to room temperature to prepare a cream.

[Table 9]

[Examples 5 to 7]

[Table 10]

Embodiments 8 and 9

[Table 11]

Examples 10 to 14

[Table 12]

Embodiments 15 and 16

[Table 13]

[Examples 17 to 19]

[Table 14]

[0048]

According to the present invention, the effect of promoting the production of the constituent protein of the epidermal cell adhesion factor desmosome and the effect of suppressing the production of the constituent protein of the stratum corneum envelope can improve rough skin, activate skin cells, and prevent skin aging. The present invention provides a highly safe skin external preparation composition that has the effect of giving smooth and moist youthful skin by reducing wrinkles and reducing texture patterns.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 17/16 A61P 17/16 43/00 105 43/00 105 // A61K 35/56 A61K 35 / 56F Terms (Reference) 4C083 AA022 AA071 AA082 AA111 AA112 AA122 AB032 AB112 AC012 AC022 AC072 AC102 AC122 AC182 AC242 AC252 AC302 AC312 AC352 AC422 AC472 AC482 AC542 AC582 AC852 AD092 AD152 AD352 AD531 AD532 AD572 AD642 AD662 BB60 A18A89 MAA ZB222 4C087 BB17 MA01 MA02 MA63 NA14 ZA89 ZB22 4C088 AB31 NA14 ZA89 ZB22 4C206 AA01 AA02 CB12 MA01 MA02 MA04 MA83 NA14 ZA89 ZB22

Claims (2)

[Claims] 1. A desmosome-constituting protein, desmoglein, desmocholine, desmoplakin expression promoter and / or stratum corneum envelope precursor protein,
An external preparation composition for skin, comprising a substance inhibiting the expression of loriculin and involucrin. 2. A composition for external use on the skin, wherein the substance according to claim 1 contains at least one selected from geranylgeranylacetone, indole alkaloid, and bryostatin as an active ingredient.