JPH09255552A - Skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin preparation for external use capable of suppressing crease formation and preventing generation of creases and excellent in improving effects for skin roughness, dandruff, etc. SOLUTION: Tihs skin preparation for external use contains, as an effective ingredient, 0.001-10wt.% of a keratinization inhibition (e.g. 25-hydroxycholesterol) belonging to an oxycholesterol and selected from a sterol having an oxygen- containing substituent except hydroxyl group at 3 position in a cholesterol structure or its derivative structure and 6-nitrocholestelol. Further, one or more of humectants selected from among an amino acid or its derivative and a mucopolysaccharide are blended. The amount to be blended is preferably 0.001-20wt.% of the amino acid or its derivative and 0.001-10wt.% of the mucopolysaccharide. By using the keratinization inhibitor together with the humectant, a synergistic effect is enhanced and the skin preparation for external use capable of bringing out further enhanced crease improving effects and expanded and moistened skin and having durable moisturizing effect is obtained.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a skin external preparation, and more particularly to a skin external preparation which is excellent in the effects of suppressing the formation of wrinkles, preventing the occurrence of wrinkles, and improving rough skin, dandruff and the like.

[0002]

2. Description of the Related Art In the epidermis, the amount of transepidermal water evaporation decreases with age, and the water content and water retention capacity of the stratum corneum also decrease. In addition, the energy metabolism system oxygen activity in the epidermis is reduced, and the epidermal turnover rate is also reduced. Therefore, the epidermis atrophies into a dry skin state in which the stratum corneum is stratified. On the other hand, the dermis also thins with age, the papillary layer becomes flattened, and the adhesive force between the epidermis and the dermis decreases. Thus, as the skin ages, its flexibility and elasticity decrease, but changes in the physical properties of the skin, which are directly involved in the formation of these wrinkles, are caused by the connective tissue of the dermis, especially extracellular cells such as collagen and elastic fibers. Not only due to the quantitative and qualitative changes of the matrix components, but also the changes of the epidermis, especially the stratum corneum. The morphological changes on the skin surface with aging show that the number of sulci decreases, the sulci crust becomes unclear, the uniformity of sulci is disturbed, and the sulcus tends to align in a certain direction.

For example, changes in the epidermis such as atrophy of the skin due to a decrease in the proliferation function of epidermal basal cells (a decrease in the epidermal turnover rate), and a resulting stratification of the stratum corneum, a decrease in the water retention function, and the occurrence of rough skin, It becomes an important factor in the initial stage of wrinkle formation. That is, the change in the stratum corneum due to drying lowers the viscoelasticity of the skin surface, and fine wrinkles easily occur.

[0004]

In order to solve these problems, an external preparation for the skin containing a moisturizer for the purpose of preventing the stratum corneum from drying has been used for improving wrinkles. Amino acids or their derivatives and mucopolysaccharides have been used as particularly effective moisturizers, but their action is weak and it is difficult to bring out sufficient effects with a small amount of compounding. In addition, when these moisturizers are blended in a large amount, other components are relatively small, so that a sufficient product cannot be provided. Problems such as stickiness will occur.

Therefore, it is not possible to obtain a sufficient wrinkle improving effect by using only these moisturizers, and a skin external preparation having an excellent wrinkle improving effect is desired. The present invention has been made in view of the above problems of the prior art, and an object thereof is to provide a skin external preparation which is excellent in the effects of improving wrinkles and preventing, as well as rough skin, dandruff and the like.

[0006]

[Means for Solving the Problems] In order to achieve the above-mentioned object, as a result of intensive studies by the present inventors, by adding a substance having an inhibitory effect on keratinization, external use on the skin excellent in the effect of improving wrinkles. The inventors have found that an agent can be obtained, and completed the present invention. That is, the external preparation for skin according to the present invention,
It is characterized by containing one or more keratinization inhibitors.

Further, the keratinization inhibitor belongs to the oxysterols group, and has a cholesterol structure or a derivative structure.
It is preferable to select one or more selected from the group consisting of sterols and 6-nitrocholesterol having at least one oxygen-containing substituent in addition to the hydroxyl group at the position. In addition, the keratinization inhibitor is 25-hydroxycholesterol, 26-hydroxycholesterol, 19-
More preferably, it is selected from one or more of hydroxycholesterol, 22-ketocholesterol oxime, 6-ketocholesterol and 7-ketocholesterol or derivatives thereof, and 25-hydroxycholesterol is most preferable. The external preparation for skin according to the present invention contains a keratinization inhibitor in an amount of 0.001 to 10
It is preferable to blend the composition in a weight percentage.

The skin external preparation according to the present invention preferably further contains one or more moisturizers selected from the group consisting of amino acids or their derivatives and mucopolysaccharides. The external preparation for skin according to the present invention preferably contains 0.001 to 20% by weight of an amino acid and an amino acid derivative. In addition, mucopolysaccharide was added to 0.
It is preferable to add 001 to 10% by weight.

[0009]

Embodiments of the present invention will be described below in more detail. The keratinization inhibitor used in the present invention means a substance having a keratin softening effect, belongs to oxysterols, and has at least an oxygen-containing substituent other than the hydroxyl group at the 3-position on the cholesterol structure or its derivative structure. It is characterized in that it is selected from among one existing sterol and 6-nitrocholesterol. These substances have the effect of returning the aging and weighted stratum corneum to a normal level and finally softening the stratum corneum.

Examples of the keratinization inhibitor used in the present invention include 25-hydroxycholesterol, 26-hydroxycholesterol, 19-hydroxycholesterol, 22-ketocholesterol oxime, 6-ketocholesterol and 7-ketocholesterol. To be It is also possible to use a derivative in which the 3-position of these substances or other hydroxyl groups are modified by esterification or the like. Of these, 25-hydroxycholesterol has a particularly high keratinization-inhibiting effect, and it is particularly preferable to use this.

The content of the keratinization inhibitor in the present invention is preferably 0.001 to 10% by weight, more preferably 0.01 to 3% by weight, based on the total amount of the external preparation for skin. 0.
When the amount is 001% by weight or less, a sufficient effect cannot be obtained, and even when the amount is 10% by weight or more, the wrinkle improving effect cannot be further obtained. In addition to the keratinization inhibitor, it is preferable to add one or two or more moisturizers selected from the group consisting of amino acids or their derivatives and mucopolysaccharides to the external skin preparation of the present invention. By increasing the water retention by adding these moisturizers and preventing the epidermis from drying, a higher wrinkle improving effect can be obtained.
It is possible to further improve the firmness and moisturization of the skin as compared with the case where the moisturizer is blended alone.

The amino acids used in the present invention include neutral amino acids such as glycine, serine, cystine, alanine, threonine, cysteine, valine, phenylalanine, methionine, leucine, tyrosine, proline, isoleucine, tryptophan, hydroxyproline and salts thereof; Examples thereof include acidic amino acids such as aspartic acid, asparagine, glutamine and glutamic acid and salts thereof; basic amino acids such as arginine, histidine and lysine and salts thereof. Examples of the amino acid derivative include trimethylglycine, acylsarcosine and salts thereof, acylglutamic acid and salts thereof, glutathione, pyrrolidonecarboxylic acid and salts thereof, oligopeptides such as glutatin, carnosine, gramcygin S, tyrosidine A, and tyrosidine B. Can be mentioned.

The amount of the amino acid and its derivative used in the present invention is preferably 0.001 to 1 in the total amount of the skin external preparation.
20% by weight, more preferably 0.01 to 5% by weight
It is. If it is 0.001 or less, sufficient skin firmness and moisture cannot be obtained, while if it is 20% by weight or more, more skin firmness and moisture can not be obtained, and unpleasant odor is generated over time. Examples of the mucopolysaccharide used in the present invention include hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, heparin and salts thereof.

The amount of the mucopolysaccharide used in the present invention is preferably 0.001 to 10% by weight, more preferably 0.01 to 3% by weight, based on the total amount of the external preparation for skin. 0.
When it is 001 or less, sufficient firmness and moisture of the skin cannot be obtained. On the other hand, even if it is blended in an amount of 10% by weight or more, further firmness and moisture of the skin cannot be obtained, and the stickiness peculiar to mucopolysaccharide is obtained. It is not preferable because it occurs.

The external preparation for skin of the present invention is an ordinary external preparation for skin, and for example, an aqueous solution system, a solubilization system, an emulsion system, a powder dispersion system, a water-oil two-layer system, a water-oil-powder three-layer system. It can be used as a base in a wide range of systems. Further, the application of the external preparation for skin of the present invention also includes lotion, emulsion, cream, basic cosmetics such as packs, lipstick, eye shadow, makeup cosmetics such as foundation, hair cosmetics such as shampoo, rinse and hair tonic, In addition to cosmetics such as body cosmetics, fragrance cosmetics, detergents and ointments, it can be used in a wide variety of fields such as pharmaceuticals and quasi drugs.

Further, the external preparation for skin of the present invention contains, in a range that does not impair the effects of the present invention, the above-mentioned essential components and additional components, as well as components usually added to cosmetics and pharmaceuticals, such as alcohol, oil, and interface. Activators, ultraviolet absorbers, ultraviolet shielding agents, other moisturizers, thickeners, preservatives, inorganic powders, organic powders, colorants, fragrances, agents and the like can be added.

[0017]

EXAMPLES The present invention will be described in more detail by using more specific examples of the present invention. Note that the present invention is not limited to this. Further, the compounding amount is shown by weight%.

Examination of the wrinkle improving effect The cream was prepared according to the formulation shown in Table 1 below, and the wrinkle improving effect was examined.

[0019]

[Table 1] ──────────────────────────────────── Examples Comparative Examples 1 2 3 1 2 ─ ─────────────────────────────────── A. Oil phase Cetanol 0.5 0.5 0.5 0.5 0.5 Vaseline 2.0 2.0 2.0 2.0 2.0 Squalane 7.0 7.0 7.0 7.0 7.0 Self-emulsifying type glycerin monostearate 2.5 2.5 2.5 2.5 2.5 Polyoxyethylene sorbitan monostearate (20E.O) 1.5 1.5 1.5 1.5 1.5 Pantothenyl ethyl ether 0.5 0.5 0.5 0.5 0.5 Jojoba oil 5.0 5.0 5.0 5.0 5.0 25-hydroxycholesterol 2.0 2.0 2.0--B. Water phase Propylene glycol 5.0 5.0 5.0 5.0 5.0 Glycerin 5.0 5.0 5.0 5.0 5.0 Montmorillonite 5.0 5.0 5.0 5.0 5.0 Sodium hyaluronate-0.3--0.3 Sodium pyrrolidonecarboxylate--0.3--Potassium hydroxide 0.3 0.3 0.3 0.3 0.3 Water residue Residual residue Residual Residual ──────────────────────────────────── (Process) A (oil phase) and B (water) Phase) Each is heated to 70 ° C. and completely dissolved. Add A to B and emulsify with an emulsifier. The emulsion was cooled using a heat exchanger to obtain a cream.

The wrinkle improving effect was evaluated according to the following method. [Evaluation Method] The skin surface morphology of the female panelist's face was replicated using a silicone resin replica method, and observed under a microscope (17 times). As a result, 20 panelists who were judged to be 1 or 2 from the wrinkled state of the skin were examined based on the following criteria. 20 panelists were divided into 4 groups (5 persons in each group), and the cream of Table 1 was applied twice a day to half of the face. The creams applied to each group are shown in Table 2. After 4 weeks, a replica was taken again, the skin condition was observed, and the evaluation was performed again according to the following criteria. [Criteria] 1: There are two or more thick and deep wrinkles. 2: There are thick and deep wrinkles. 3: wrinkled 4: wrinkle reserve group present 5: Almost no wrinkles. In addition, the wrinkle reserve group is a group in which the skin groove and the cuticle have developed,
It is not a clear wrinkle, but it is expected to become a wrinkle in the future.

[0021]

[Table 2] ──────────────────────────────────── Left half right half ────── ─────────────────────────────── 1 group Example 1 Example 2 2 group Example 1 Example 3 3 group Example 1 Comparative Example 1 4 groups Example 1 Comparative Example 2 ─────────────────────────────────────

The results are shown in Table 3.

[Table 3] ──────────────────────────────────── 1 group 2 groups 3 groups 4 groups Evaluation Left Right left right left right left right ──────────────────────────────────── 1 0 0 0 0 0 0 2 0 1 2 0 0 0 0 0 2 2 0 2 3 1 0 1 1 0 0 1 0 2 4 2 2 1 1 1 2 0 3 0 5 2 3 3 3 4 3 0 2 0 ──────────── ────────────────────────

As is clear from the above results, in the groups 3 and 4 coated with Example 1 and Comparative Examples 1 or 2, almost no wrinkle improving effect was observed on the right half of the face coated with Comparative Example 1 or 2. unacceptable. On the other hand, in the left half surface to which Example 1 was applied, wrinkles were almost disappeared, showing a high improvement effect.

In addition, the wrinkle-reducing effect is observed in any of the groups 1 and 2 to which Example 1 and Example 2 or 3 are applied. In particular, in Examples 2 and 3 in which an amino acid or mucopolysaccharide was added, A high wrinkle improving effect is recognized. Therefore, a skin external preparation having a wrinkle improving effect can be obtained by adding a keratinization inhibitor, and a skin moisturizing agent having a higher wrinkle improving effect can be obtained by adding a moisturizing agent thereto. Is possible.

Examination of skin quality improving effect Further, the present inventors examined the skin quality improving effect by using the above-mentioned Examples 1 to 3 and Comparative Examples 1 and 2. The evaluation was performed according to the following criteria. [Evaluation Criteria] (Skin firmness) Effectiveness: Hardness of skin was severe Effectiveness: Firmness of skin was slightly effective: Effectiveness of skin was slightly firmed Ineffective: There was no change in firmness of skin ( Moisture) Effective: Moisturized skin became very moisturized Effective: Moisturized skin was moisturized, slightly moisturized: No change in moisturized skin, not dry Ineffective: Moisture decreased [Determination] ⊚: 80% or more of the subjects exhibiting excellent efficacy and efficacy ○: 50 to 60 of the subjects exhibiting excellent efficacy and efficacy
% Δ: 30 to 50 of the test subjects showed marked efficacy and efficacy
% ×: 30% or less of the subjects showing marked efficacy and efficacy

The results are shown in Table 4.

[Table 4] ──────────────────────────────────── Example 1 Example 2 Example 3 Comparison Example 1 Comparative Example 2 ──────────────────────────────────── Skin tone ◎ ◎ ◎ ◎ △ ○ Skin Moisture ◎ ◎ ◎ △ ○ Moisture on the next morning ○ ◎ ◎ × △ ────────────────────────────────── ───

As is clear from the above results, Comparative Example 1 does not provide satisfactory improvement in skin firmness and moisture. Further, in Comparative Example 2, since sodium hyaluronate is blended, the firmness and moisturization of the skin at the time of application can be satisfied, but the moisturization is weak and the moistness disappears the next morning.

On the other hand, according to Examples 1 to 3 of the present invention,
The firmness and hydration of the skin are excellent, and the hydration of the skin on the next morning is also felt, and particularly when the amino acid and mucopolysaccharide are blended, high hydration continuity is exhibited. As a result, it is clear that the keratinization inhibitor itself contributes to the firmness and moisturization of the skin, and the keratinization inhibitor and the moisturizer have a synergistic effect, and the firmness and moisturization provided by the moisturizer are sustained for a long period of time. became. Therefore,
According to the external preparation for skin of the present invention, it is possible to obtain an external preparation for skin which is satisfactory for firmness and moisturization of the skin, and further by adding a moisturizing agent such as amino acid and mucopolysaccharide, the external preparation for skin having a high moisturizing effect Can be obtained.

Hereinafter, more specific formulation examples of the present invention will be shown. The present invention is not limited to this. Further, the compounding amount is shown by weight%.

Formulation Example 1 Cream A. Oil phase Stearic acid 10.0% by weight Stearyl alcohol 4.0 Butyl stearate 8.0 Stearic acid monoglycerin ester 2.0 25-Hydroxycholesterol 2.0 Perfume 0.4 Preservative A suitable amount B. Aqueous phase Sodium hyaluronate 0.5 Glycerin 4.0 Potassium hydroxide 0.4 Trisodium edetate 0.05 Purified water Residual (Production method) A. An oil phase and B.I. The aqueous phases are each heated to 70 ° C. and completely dissolved. Add A to B and emulsify with an emulsifier.
The emulsion was cooled using a heat exchanger to obtain a cream.

Formulation Example 2 Cream A. Oil phase Cetanol 4.0 wt% Vaseline 7.0 Isopropyl myristate 8.0 Squalane 15.0 Stearic acid monoglycerin ester 2.2 POE (20) sorbitan monostearate 2.8 25-Hydroxycholesterol 2.0 Perfume 0 .3 Antioxidant Appropriate amount Preservative Appropriate amount B. Aqueous phase Glycerin 10.0 Sodium hyaluronate 0.02 Dipropylene glycol 4.0 Sodium pyrrolidonecarboxylate 1.0 Disodium edetate 0.01 Purified water Residue (manufacturing method) A cream was obtained according to the formulation example 1.

Formulation Example 3 Cream A. Oil phase Squalane 5.0% by weight Oleyl oleate 3.0 Vaseline 2.0 Sorbitan sesquioleate 0.8 Polyoxyethylene oleyl ether (20EO) 1.2 25-Hydroxycholesterol 0.03 Perfume 0.3 Preservative Suitable Amount B. Aqueous phase 1,3 Butylene glycol 4.5 Sodium hyaluronate 0.5 Ethanol 3.0 Carboxyvinyl polymer 0.2 Potassium hydroxide 0.1 Sodium hexametaphosphate 0.05 Purified water Residual (manufacturing method) Got the cream.

Formulation Example 4 Foundation A. Oil phase Cetanol 3.5% by weight Deodorized lanolin 4.0 Jojoba oil 5.0 Vaseline 2.0 Squalane 6.0 Stearic acid monoglycerin ester 2.5 POE (60) hydrogenated castor oil 1.5 POE (20) cetyl ether 1.0 25-Hydroxycholesterol 0.1 Perfume 0.3 Preservative Appropriate amount B. Aqueous phase Propylene glycol 10.0 Sodium hyaluronate 0.5 Preparation powder 12.0 Trisodium edetate 0.2 Purified water Residue (Production method) A foundation was obtained according to Preparation Example 1.

Formulation 5 Lotion A. Alcohol phase Ethanol 5.0 wt% POE oleyl alcohol ether 2.0 2-Ethylhexyl-P-dimethylaminobenzoate 0.18 25-Hydroxycholesterol 0.2 Perfume 0.05 B.I. Aqueous phase 1,3 Butylene glycol 9.5 Sodium pyrrolidonecarboxylate 0.5 Sodium hyaluronate 0.5 Glycerin 5.0 Purified water Residue (production method) A. The alcohol phase was added to B.I. It was added to the aqueous phase and solubilized to obtain a lotion.

Formulation Example 6 Pack (1) Polyvinyl alcohol 10.0 wt% (2) Polyethylene glycol (molecular weight 400) 0.4 (3) Glycerin 3.0 (4) Ethanol (95%) 8.0 (5) 25-Hydroxycholesterol 0.2 (6) Sodium hyaluronate 0.5 (7) Preservative 0.1 (8) Perfume 0.1 (9) Purified water Appropriate amount (Production method) At room temperature (4) (7) ( 8) is mixed and dissolved,
(1) (2) (3) and (5) (6) (9) were mixed and dissolved at 80 ° C., added with stirring, and then allowed to cool to room temperature to obtain a pack.

Formulation Example 7 Lipstick (1) Castor oil 20.0% by weight (2) Cetyl alcohol 20.0 (3) Beeswax 5.0 (4) Candelilla wax 30.0 (5) Sodium hyaluronate 0.5 (6) Squalane 13.0 (7) Carnauba wax 5.0 (8) Pigment 5.0 (9) 25-Hydroxycholesterol 0.01 (10) Fragrance Suitable amount (Production method) (1) to (9) at 80 ° C After melting, the mixture was poured into a mold, allowed to cool to room temperature, and then taken out from the mold to obtain a stick-shaped lipstick.

[0037]

As described above, since the external preparation for skin of the present invention contains a keratinization inhibitor such as 25-hydroxycholesterol, it is excellent in the effect of preventing wrinkles and improving wrinkles. In addition, by blending an amino acid or its derivative, which is a moisturizer, and mucopolysaccharide together with a keratinization inhibitor, the effects of both are synergistically enhanced, and a higher wrinkle improving effect and skin firmness and moisturizing are obtained, and yet moisturizing. It is possible to obtain a skin external preparation having a long-lasting effect.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display area A61K 31/56 ADA A61K 31/56 ADA

Claims (8)

[Claims] 1. A skin external preparation containing one or more keratinization inhibitors. 2. The external preparation for skin according to claim 1, wherein
The keratinization inhibitor belongs to oxysterols, and is one or two selected from the group consisting of sterols and 6-nitrocholesterol having at least one oxygen-containing substituent other than the hydroxyl group at the 3-position on the cholesterol structure or on the derivative structure thereof. A skin external preparation characterized by being selected from one or more species. 3. The external preparation for skin according to claim 2,
Keratinization inhibitor is 25-hydroxycholesterol, 26
-Hydroxycholesterol, 19-hydroxycholesterol, 22-ketocholesterol oxime, 6
-Ketocholesterol and 7-ketocholesterol or a derivative thereof selected from one or two or more kinds, and an external preparation for skin. 4. The external preparation for skin according to claim 3,
An external preparation for skin, wherein the keratinization inhibitor is 25-hydroxycholesterol. 5. The external preparation for skin according to claim 1, which contains 0.001 to 10% by weight of a keratinization inhibitor. 6. The external preparation for skin according to claim 1, further comprising one or more moisturizers selected from the group consisting of amino acids or their derivatives and mucopolysaccharides. External skin preparation. 7. The external preparation for skin according to claim 6,
0.001 to 20% by weight of amino acids and amino acid derivatives
A skin external preparation characterized by being blended. 8. The external skin preparation according to claim 6,
An external preparation for skin, comprising 0.001 to 10% by weight of mucopolysaccharide.