JP2001163758A - Preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a preparation for external use for skin, having an excellent wrinkle-improving effect. SOLUTION: This preparation is characterized by incorporating (A) 1 kind of >=2 kinds selected from agaric acid and its salts, and lipoic acid and its salts, and (B) 1 kind or >=2 kinds selected from triterpenes, sphingoid-based compounds, slindac, an oxidized type CoA and its salts, and organic silicon compounds such as a lower alkylsilanol and a peptide derivative of the lower alkylsilanol.

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 prevents aging of the skin including wrinkles and gives smooth, moist and youthful skin.

[0002]

2. Description of the Related Art Conventionally, "wrinkles" have been cited as one of the skin cosmetic problems along with spots and freckles. It is known that "wrinkles" are caused by dryness of the skin, the effects of ultraviolet rays, and aging, which deteriorate the skin condition. There are still many unclear points about the mechanism of wrinkles, but at the epidermal level of the skin, long-term UV irradiation affects skin aging, such as drying and a decrease in the moisturizing power of the stratum corneum. And
It is considered that the elastic fibers are degenerated, that is, the elasticity decreases due to the collapse of the elastin network. Therefore, skin care using a product containing an ultraviolet ray inhibitor or a moisturizer has been actively performed, but it only prevents wrinkles and its effect is not sufficiently satisfactory.

[0003] In recent years, many cosmetics have been proposed to prevent skin aging such as "wrinkles", and retinoic acid (Kligman, LH, Duo,
CH, Kligman, AM, Connect Tis
sweet Res 12: 139-150, 1984),
Retinol (vitamin A) and the like have been reported. However, these active ingredients have problems in skin irritation, stability, and the like, and their effects are hardly sufficient. On the other hand, hydroxycarboxylic acids such as glycolic acid and agaricic acid (JP-A-6-139947, Japanese Patent No. 2533339) are widely used for the purpose of enhancing the moisturizing function, but satisfactory effects cannot be obtained by themselves. .

Further, wrinkle improving agents using plant extracts and the like have been proposed, but their effects have been insufficient (JP-A-6-9442 and JP-A-8-268859).

Further, methyltrisilanol and N-acetylcysteine (Japanese Patent Application Laid-Open Nos. 62-249909 and 10-53517), which suppress the cross-linking of dermis collagen, have been proposed, but they alone have a sufficient effect. Is not exhibited.

[0006] Therefore, coenzyme A [C ₂₁ H ₃₆ N ₇ , which does not have the above-mentioned problems, has activation of skin cells, promotes metabolism, has a wound healing effect, and has an excellent anti-aging effect on skin.
O ₁₆ P ₃ S, coenzyme A, hereinafter simply referred to as “CoA”] and salts thereof have been developed (JP-A-50-31051). In addition, this CoA and / or its salt is unstable in the preparation, and if it is mixed with cosmetics, it adversely affects other components such as color tone deterioration. Therefore, the stabilization of CoA and / or its salt is examined. It has been found that oxidized CoA synthesized by the oxidation reaction of a salt shows high stability in a preparation, and has an effect of healing wounds and an effect of improving fine lines, shine and texture of the skin (Japanese Patent Application Laid-Open No. 2-49729). No. 9-268119).

[0007] However, a skin external preparation which can further prevent skin aging including wrinkles, particularly a skin external preparation which has a high effect of improving wrinkles and which can realize the effect quickly, has been desired.

[0008] The present invention has been made to meet the above-mentioned demands, and has as its object to provide a skin external preparation capable of promptly realizing the effect of improving wrinkles and having an excellent effect of improving the effect.

[0009]

Means for Solving the Problems and Embodiments of the Invention The present inventors have conducted intensive studies in order to achieve the above object, and as a result, (A) agaric acid having a collagen cross-linking inhibitory action, a salt thereof, and lipoic acid. And (B) triterpenes, sphingoid compounds, sulindac, oxidized C
oA (the SH groups at the ends of two CoA molecules
-S-bonded CoA dimer) and salts thereof, and prevention and improvement of skin aging by combination with one or more selected from lower alkylsilanols and organosilicon compounds of peptide derivatives of lower alkylsilanols. The effect is higher than that of the component (A) or the component (B) alone, the effect of improving wrinkles is high, the effect can be realized quickly, and the effect of giving a smooth, moist and youthful skin is excellent. Thus, the present invention has been accomplished.

Hereinafter, the present invention will be described in more detail.
The external preparation for skin of the present invention comprises (A) one or two or more selected from agaric acid, lipoic acid and salts thereof, and lipoamide having a collagen cross-linking inhibitory action, and (B) triterpenes, sphingoid compounds, Sulindac, one type selected from oxidized CoA (CoA dimer in which terminal SH groups of CoA2 molecules are bonded to each other by S—S) by oxidation and salts thereof, and lower alkyl silanols and organosilicon compounds of peptide derivatives of lower alkyl silanols Alternatively, it is characterized by containing two or more kinds.

The component (A) used in the present invention includes:
Agaric acid or a salt thereof, lipoic acid or a salt thereof, and lipoamide represented by the following formula. Examples of the salts of agaric acid and lipoic acid include metal salts such as sodium salt, lithium salt, potassium salt, calcium salt, magnesium salt, and zinc salt.

[0012]

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The amount of the component (A) is preferably 0.005 to 5% (% by mass, the same applies hereinafter), more preferably 0.01 to 2%, based on the total amount of the external preparation for skin. 0.
If it is less than 005%, the effect of improving the effect of the component (A) is insufficient, and if it exceeds 5%, no further effect is usually exhibited.

The present invention relates to the above-mentioned (A) component and (B) component as triterpenes, sphingoid compounds, sulindac, oxidized CoA (CoA dimer wherein the SH groups at the terminals of the CoA2 molecule are S--S bonded by oxidation. ) Or a salt thereof, and an organosilicon compound of a lower alkylsilanol and a peptide derivative of the lower alkylsilanol, which are used alone or in an appropriate combination of two or more.

Here, examples of the triterpenes include α-amylin group, β-amylin group, lupeol group, nosterin group, squalene group, terpene hydrocarbons having 30 carbon atoms which cannot be classified into these, alcohols, and the like. In the case of the present invention, among these, the lupeol group is particularly preferable, and specific examples of the lupeol group include betulin, lupeol, and betulinic acid. Among these, betulinic acid represented by the following structural formula is particularly preferable. It is suitable.

[0016]

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Examples of the sphingoid-based compound include sphingolipids having 16 to 20 carbon atoms.
More specifically, sphingolipids include ceramide, glycosphingolipid, and sphingolipid. Here, the ceramide is a ceramide II represented by the following formula:
A fatty acid is an acid amide bond to an amino group of a sphingo base (sphingoid) as follows, and is classified into various types according to the type of acyl group of the following formula, the presence or absence of a hydroxyl group, and its position. In the case of the present invention, Ceramides I to VI localized on skin, hair, wool and the like are particularly preferred. Furthermore,
As the glycosphingolipid, galactosylceramide and the like are preferable. In addition, sphingomyelin and the like are particularly preferable as sphingolipids, and in the case of the present invention, sulindac represented by the following formula is also suitably used.

[0018]

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Subsequently, the oxidized CoA represented by the following formula is a dimer of CoA in which the SH groups at the ends of two CoA molecules are oxidized to form SS bonds, and as a salt thereof, formed at the phosphate group. Metal salts such as sodium salt, lithium salt, potassium salt, calcium salt, magnesium salt, zinc salt and the like can be mentioned.

[0020]

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As the organosilicon compound, lower alkylsilanols and peptide derivatives of lower alkylsilanols represented by the following general formula are used.

Lower alkyl silanol R _n Si (OH) _4-n (wherein R is a linear or branched alkyl group having 1 to 4 carbon atoms, and n is 1 or 2)

[0023]

Embedded image (In the formula, R and n are the same as described above, and peptide is a peptide residue, particularly a peptide residue having a molecular weight of 100 to 10,000.)

The lower alkylsilanetriol or di-lower alkylsilanediol includes, for example, dimethylsilanediol, methylsilanetriol, diethylsilanediol, ethylsilanetriol, dipropylsilanediol, propylsilanetriol, diisopropylsilanediol, isopropylsilanetriol. , Dibutylsilanediol, butylsilanetriol, diisobutylsilanediol, isobutylsilanetriol, di (sec-butyl) silanediol, sec-butylsilanetriol, di (tert-butyl) silanediol, tert-butylsilanetriol and the like. . In addition, for those peptide derivatives, collagen, elastin, keratin, prepared by various methods,
It is a compound that can be prepared by a general binding reaction with a protein hydrolyzate such as silk, milk, soybean, and wheat, and is commercially available under the name of Promois (Seiwa Kasei) or the like, and is a readily available compound. The molecular weight of the peptide portion of the peptide derivative is about 100 to 10,000, especially about 1.0
Those having a value of 00 or less are preferable.

The amount of component (B) is preferably 0.001 to 5%, more preferably 0.01 to 2%, based on the total amount of the external preparation for skin. If less than 0.001%
The effect of preventing skin aging is insufficient, and if it exceeds 5%, no further effect is usually exhibited.

The external preparation for skin of the present invention includes the above (A),
In addition to the component (B), any component known to have a skin aging preventing effect different from the components (A) and (B), for example, retinoic acid, retinol, β-glycyrrhetinic acid, stearyl glycyrrhetinate, dipotassium glycyrrhizinate ,
Magnesium ascorbate phosphate, tocopherol,
By blending tocopherol acetate, pantothenyl ethyl ether, allantoin, hyaluronic acid, seaweed extract, etc., a more effective wrinkle improving effect can be obtained.

Further, in order to prevent ultraviolet rays and drying which cause wrinkles, ultraviolet absorbers such as benzoates, salicylic acids, cinnamic acids, dibenzoylmethane derivatives, titanium oxide and zinc oxide. UV scattering agent,
Glycerin, amino acids, amino acid derivatives, moisturizing agents such as sodium pyrrolidone carboxylate, and also polyphenols, tannins, or the like having an antioxidant effect to prevent oxidation that causes aging of cells in the body. It is even better to mix certain animal and plant extracts.

In addition to the above essential components (A) and (B), the skin external preparation of the present invention may contain optional ingredients usually used in skin external preparations such as surfactants, oils and alcohols. Humectants, thickeners, preservatives, antioxidants, chelating agents, pH adjusters, fragrances, pigments, ultraviolet absorbers / scatterers, vitamins, amino acids, water, and the like. The optional components are not limited to these.

The skin external preparation of the present invention can be prepared according to a usual method, and includes various creams, emulsions, lotions,
It can be prepared and used as various skin external preparations such as serums, packs, patches and ointments. The dosage form is not particularly limited.

[0030]

EXAMPLES The present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. The compositions of the external preparation for skin in Examples and Comparative Examples are shown in% (% by mass). The effect of suppressing collagen crosslinking and the effect of improving wrinkles were evaluated by the following methods.

Collagen Crosslinking Inhibition Test As a collagen sample, type I acid-soluble collagen (Elastin Products Company) was used.
) And atelocollagen (manufactured by Wako Pure Chemical Industries, Ltd.) were used as substrates. The conditions for the Maillard crosslinking reaction include:
Collagen concentration is 30 mg / ml in the case of acid soluble collagen and 10 mg in the case of atelocollagen.
/ Ml, glucose concentration 24 mg / ml,
The reaction was carried out at 37 ° C. for 2 weeks in a 0.5 M potassium phosphate buffer (pH 7.2). The drug concentration is
0.5%. Analysis of the crosslinked product was performed by Bromcian degradation in accordance with the method of Kotani et al. (Biochemical Experiment Course 1 Chemistry of Protein II), and then Laemmli, U.S.A. K et al. (Nature 227, 680-685 (19
70)) and subjected to SDS-PAGE to measure the molecular weight of 100K to 200K with a densitometer (Shimadzu Corporation)
CS-9000) for comparison and evaluation. The crosslinking inhibition rate was calculated by dividing the amount of cross-linked product of the drug-added product by the amount of cross-linked product of the non-drug-added product, and subtracting this value from 1 to convert it to%. The control was the one before the start of the reaction.

[0032]

(Equation 1)

Wrinkle improvement effect confirmation test Fifteen women (20 to 40 years old) worried about wrinkles were tested twice a day (morning and night) by using a wrinkle-worried part. . The condition of the skin one month after application was evaluated by using the degree of improvement in wrinkles as an index. Three or less people who were slightly more effective were evaluated as x, 4 to 6 as △, 7 to 12 as 、, 13 to 15
The person was evaluated as ◎. At the same time, a questionnaire survey was conducted to determine whether wrinkles were improved, and the number of people who felt that the wrinkles were improved was shown two weeks later and one month later.

[Experimental Examples] The inhibitory effect of collagen crosslinking on the drugs shown in Table 1 was examined by the above method, and the results shown in the same table were obtained. From these results, it was found that the component (A) of the present invention exhibited a strong inhibitory effect on any collagen substrate, and had a stronger effect than known ones.

[0035]

[Table 1]

Next, Examples and Comparative Examples are shown. Tables 2 to 4 show the compositions of the fragrances A to C used in the following examples.

[0037]

[Table 2]

[0038]

[Table 3]

[0039]

[Table 4]

[Examples 1 to 4 and Comparative Examples 1 to 4] Creams having the compositions shown in Table 5 below were prepared, and the effect of improving wrinkles was evaluated by the above evaluation method. The preparation method used was a method in which the aqueous component and the oil component were each heated and dissolved at 70 ° C., mixed, emulsified, and cooled to room temperature. The fragrance component was added during the cooling. The results of each evaluation are shown in Table 5 below.

[0041]

[Table 5]

As is clear from the results shown in Table 5, Examples 1 to 4 according to the present invention have a higher wrinkle-reducing effect than Comparative Examples 1 to 4 which are out of the scope of the present invention, and furthermore, their expression. Was found to be early.

Examples 5 to 42 in which creams, emulsions, lotions, serums, and packs containing the components (A) and (B) according to the present invention are shown below.

Examples 5 to 14 Creams having the respective compositions shown in Table 6 below were prepared by a conventional method. It was found that each of these compositions has a high wrinkle-reducing effect, and the expression is fast.

[0045]

[Table 6]

Examples 15 to 21 Emulsions having the compositions shown in Table 7 below were prepared. In the production method, an oil phase, an oil phase composed of a surfactant, an aqueous phase composed of a humectant, purified water, etc. were mixed and dissolved at 70 ° C., respectively, and preliminary emulsification was performed while stirring the aqueous phase. Next, an emulsifier (homomixer) treatment is performed,
The emulsified particles were homogenized, degassed, cooled and finished at 35 ° C. The properties of the emulsion are as follows. It was found that each of these compositions has a high wrinkle-reducing effect, and the expression is fast.

[0047]

[Table 7]

[Examples 22 to 26] Lotions having the compositions shown in Table 8 below were prepared by a conventional method. It was found that each of these compositions has a high wrinkle-reducing effect, and the expression is fast.

[0049]

[Table 8]

[Examples 27 to 31] Essences having the respective compositions shown in Table 9 below were prepared. In the production method, squalane, glycerin, polyglycerin fatty acid ester and the like were heated to prepare a uniform non-aqueous emulsion. Next, twice the amount of purified water was added to the non-aqueous emulsion, followed by mixing and stirring to obtain a preliminary emulsion. This was atomized at 1000 bar with a microfluidizer (trade name, manufactured by Microfluidic Corporation), and then oxidized CoA sodium salt, a humectant,
It was prepared by adding other components such as a polymer and the remaining purified water. Example 29 was prepared by a conventional method.
It was found that each of these compositions has a high wrinkle-reducing effect, and the expression is fast.

[0051]

[Table 9]

Examples 32 to 36 Cosmetic solutions having the compositions shown in Table 10 below were prepared by a conventional method. It was found that each of these compositions has a high wrinkle-reducing effect, and the expression is fast.

[0053]

[Table 10]

Examples 37 to 40 Packs having the compositions shown in Table 11 below were prepared by a conventional method. It was found that each of these compositions has a high wrinkle-reducing effect, and the expression is fast.

[0055]

[Table 11]

Examples 41 and 42 Sheet packs having the compositions shown in Table 12 below were prepared by a conventional method. It was found that each of these compositions has a high wrinkle-reducing effect, and the expression is fast.

[0057]

[Table 12] 1) 1 part by weight of the sheet is impregnated with 7 parts by weight of the impregnating liquid. 2) 1 part by weight of the sheet is impregnated with 10 parts by weight of the impregnating liquid.

[0058]

The external preparation for skin of the present invention has an excellent effect of improving wrinkles.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 7/00 A61K 7/00 GF WFterm (Reference) 4C083 AA122 AC012 AC022 AC072 AC122 AC301 AC302 AC342 AC422 AC432 AC482 AC582 AC642 AC851 AC852 AC861 AC862 AC901 AC902 AC911 AC912 AD092 AD112 AD152 AD172 AD272 AD332 AD352 AD391 AD392 AD411 AD412 AD471 AD472 AD531 AD532 AD572 BB41 CC02 CC04 CC05 CC07 DD12 DD27 DD31 EE12

Claims (1)

[Claims] (A) one or two selected from agaric acid and its salts, lipoic acid and its salts, and lipoamide
And at least one species selected from (B) triterpenes, sphingoid compounds, sulindac, oxidized CoA and salts thereof, and lower alkylsilanols and organosilicon compounds of lower alkylsilanol peptide derivatives. An external preparation for skin, characterized by comprising: