JPH08175959A - Skin cosmetic - Google Patents

Abstract

PURPOSE: To provide a skin cosmetic containing a benzoic acid anilide compound and effective for suppressing the wrinkling and pigmentation of the skin. CONSTITUTION: This cosmetic contains a compound of formula (R<1> is H or t-butyl; R<2> is H, a 1-5C alkyl or an acyl) or its salt as an active component in an amount of 0.001-20wt.%, preferably 0.05-5wt.%. The suppression effect on the wrinkle and spots can be improved by incorporating the cosmetic with other conventional anti-inflammatory agent (e.g. allantoin), an antioxidant, etc. It can be prepared in the form of an O/W-type or W/O-type emulsified cosmetic, cream, cosmetic milky lotion, face lotion, oily cosmetic, pack, foundation, etc., by properly compounding with conventional cosmetic components. An example of the compound of formula is 4-hydroxy-N-(2-hydroxyphenyl) benzoic acid amide.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a skin cosmetic, and more particularly to a skin cosmetic which suppresses skin wrinkling and pigmentation and prevents skin aging.

[0002]

2. Description of the Related Art Maintaining healthy and beautiful skin has become a serious concern for people of all ages.

However, the skin is aged, ultraviolet rays, temperature and humidity,
It is affected by diseases, stress, eating habits, etc., causing aging, deterioration of various functions, and various other troubles. Typical of skin aging is the formation of "wrinkles" and "spots" (pigmentation), which are one of the major cosmetic problems especially for women.

Of these, wrinkles, which are one of the problems of the dermis, are aging of the skin due to aging and sunlight (photoaging).
Caused by. Although the mechanism of aging is not clear, in the case of the skin, it is located in the outermost layer of the body and plays a role of the front line of biological defense.Accordingly, the accumulation of disorders due to environmental factors has a significant effect on the skin aging phenomenon. it seems to do. In particular, ultraviolet rays are considered to be the largest environmental factor involved in skin aging and wrinkle formation. That is, it is known that free radicals (particularly active oxygen) produced by ultraviolet rays induce not only acute inflammation such as sunburn but also photoaging by being chronically repeated. Specifically, various free radicals and active oxygen (superoxide, hydroxy radicals, singlet oxygen, etc.) generated by ultraviolet rays are DNA-protein crosslinks (crosslinking bonds) of dermal components, obstacles to protein crosslinks such as collagen and elastin, It is considered that denaturation, inactivation of antioxidant enzymes such as SOD, peroxidation of membrane lipids of cell components and deterioration of cell function due to this are caused, and as a result, aging and wrinkles are formed (Fragrance Journal, Volume 11, 49
-54, 1992).

Therefore, in order to prevent the formation of such wrinkles, conventionally, an antioxidant such as vitamin E has been used (Japanese Patent Laid-Open No. 61-215309, Japanese Patent Laid-Open No. 62-2631).
No. 10), the use of various plant extracts (JP-A-62-6).
1924, JP-A-63-174911, JP-A-6-65043, etc.), the use of extracellular matrix control agents such as collagen (JP-A-4-74016, JP-A-3-20206, etc.) ), The use of retinoic acid or α-hydroxy acid has been proposed.

[0006] However, the effect of preventing and improving the wrinkles of such conventional means is not sufficient.

On the other hand, pigmentation such as spots occurs due to an increase in melanin pigment synthesized by melanocytes in the epidermis, and it is pointed out that ultraviolet rays, female hormones, genetic factors, etc. are involved in the pathogenic mechanism. However, it has not been fully clarified yet. Therefore, drugs for the purpose of suppressing the production of melanin and reducing established melanin have been studied as whitening agents, and arbutin, kojic acid, vitamin C, licorice extract (Japanese Patent Laid-Open No. 63-23809). Japanese Laid-Open Patent Publication No. 1-1497
No. 06), Cuckon (JP-A-64-16709), hydroxystilbene (JP-A-64-38009).
No.), 3-hydroxychromone (JP-A-55-11)
1410, JP-A-55-143908),
Isoflavones (JP-A-58-225004) and the like have been developed. However, the fact is that there are almost no substances that are highly compoundable in actual cosmetics and have a high whitening effect.

[0008]

SUMMARY OF THE INVENTION It is, therefore, an object of the present invention to provide a skin cosmetic effective for preventing and improving skin aging, that is, formation of wrinkles and pigmentation.

[0009]

In view of such circumstances, the present inventors have conducted diligent research and as a result, when an anilide benzoate represented by the following general formula (1) or a salt thereof is blended, excellent wrinkles are obtained. Further, they have found that a skin cosmetic having an effect of preventing and improving the formation of pigmentation can be obtained and completed the present invention.

That is, the present invention is represented by the following general formula (1)

[0011]

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A benzoyl anilide or a salt thereof represented by the formula: wherein R ¹ represents a hydrogen atom or a t-butyl group, and R ² represents a hydrogen atom or an alkyl or acyl group having 1 to 5 carbon atoms. It is intended to provide a skin cosmetic containing the same.

The benzoic acid anilide used in the present invention is represented by the above-mentioned general formula (1).
Specific examples of R ² include hydrogen atom; methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group,
Isobutyl group, sec-butyl group, t-butyl group, n-
Alkyl groups such as pentyl group and isopentyl group; formyl group, acetyl group, propionyl group, n-butyryl group, isobutyryl group, n-valeryl group, isovaleryl group, pivalyl group and other acyl groups, among which hydrogen atom Is particularly preferable.

Among the benzoic acid anilides represented by the general formula (1), specifically 4-hydroxy-N- is particularly preferable.
(2-Hydroxyphenyl) benzoic acid amide (Compound 1), 4-hydroxy-N- (3-hydroxyphenyl) benzamide (Compound 2), 4-hydroxy-N-
(4-Hydroxyphenyl) benzamide (Compound 3), 3,5-di-t-butyl-4-hydroxy-N-
(4-Hydroxyphenyl) benzamide (Compound 4), 3,5-di-t-butyl-4-hydroxy-N-
(3-Hydroxyphenyl) benzamide (Compound 5), 3,5-di-t-butyl-4-hydroxy-N-
(2-Hydroxyphenyl) benzamide (Compound 6)
However, the present invention is not limited to these.

A part of the benzoic acid anilides (1) is a known compound and can be produced by a known method [Reference: JP-A-6-72866 and Japanese Patent Application No. 6-126].
278]. However, it is not known that the compound has a skin antiaging effect.

The anilide benzoates can be produced by the production means.
Alternatively, depending on the purpose of use, it may be stabilized in the form of a hydrate, a solvate, or a salt, and any of these may be used in the present invention. Examples of the salt include alkali metal salts such as sodium and potassium, alkaline earth metal salts, amine salts and the like.

The amount of the above-mentioned anilide benzoate or a salt thereof in the skin cosmetic of the present invention is generally 0.001 to
The amount is preferably about 20% by weight, more preferably 0.05 to 5% by weight.

The skin cosmetic of the present invention contains, in addition to the above essential components,
The addition of known anti-inflammatory agents such as allantoin, vitamin E derivatives, glycyrrhizin and ascorbic acid derivatives, antioxidants, etc. can improve the effect of suppressing the formation of wrinkles and spots.

Further, the skin cosmetic composition of the present invention contains, if necessary, components that are added to ordinary cosmetic compositions, such as moisturizers such as hyaluronic acid and ceramide, ultraviolet absorbers, alcohols, chelating agents, vaseline, Solid and semi-solid oils such as lanolin, ceresin, microcrystalline wax, carnauba wax, candelilla wax, higher fatty acids, higher alcohols; water-soluble and oil-soluble polymers; inorganic and organic pigments, inorganic and organic treated with silicone or fluorine compounds Colorants such as pigments and organic dyes; anionic activators, cationic activators, nonionic activators, surfactants such as dimethylpolysiloxane / polyoxyalkylene copolymers and polyether modified silicones; other water, antiseptic Agents, antioxidants, pigments, thickeners, pH adjusters, fragrances, blood circulation promoters,
A cooling sensation agent, an antiperspirant, a bactericidal agent, a skin activating agent, etc. can be appropriately added within a range that does not impair the effects of the present invention.

The cosmetics of the present invention can be used in various applications and forms such as oil / water type, water / oil type emulsified cosmetics, creams, lotions, lotions, oily cosmetics, packs, foundations and the like. You can Further, the cosmetic of the present invention can be manufactured by a conventional method. The skin cosmetic of the present invention is not limited to general skin cosmetics, but includes quasi drugs, medicated cosmetics, and the like.

[0021]

The skin cosmetic of the present invention is excellent in the effect of preventing and improving skin aging, that is, the effect of preventing and improving the formation of wrinkles and pigmentation (spots, etc.). In particular, the cosmetic of the present invention effectively suppresses the formation of wrinkles and pigmentation caused by irradiation with ultraviolet rays.

[0022]

The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

Synthesis Example 1 o-Aminophenol (10.99 g, 100.0 mmo
l) is a pyridine-chloroform (5: 1) mixed solvent (1
A solution of p-acetoxybenzoic acid chloride (10.0 g, 50.0 mmol) dissolved in chloroform (200 ml) was slowly added dropwise over 3.5 hours. After completion of dropping, the reaction was completed by further stirring for 1 hour. The reaction solution was concentrated at room temperature, ethanol (100 ml) was added to the residue and dissolved, and then methylamine 40% methanol solution (10.0 g, 14
0.0 mmol) was added dropwise and the mixture was stirred at 50 ° C. for 1 hour. The reaction solution was concentrated again under reduced pressure, and the residue was extracted with ethyl acetate. The organic layer was washed successively with 12% hydrochloric acid, distilled water, aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, a brown oily substance was obtained. This was subjected to silica gel column chromatography, eluted with a chloroform-methanol mixed solvent, concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate-n-hexane to give 4-hydroxy-n as white powder crystals. -(2-Hydroxyphenyl) benzoic acid amide (5.02 g, 45%) (Compound 1) was obtained. mp.159.1-159.7 ° C NMR: (DMSO-d ₆ ): δ; ppm 6.78-7.06 (m, 2H), 6.88 (d, 2H, J = 10Hz), 7.04 (d, 1H, J = 7H
z), 7.71 (d, 1H, J = 7Hz), 7.87 (d, 2H, J = 10Hz), 9.37 (s, 1H),
9.76 (s, 1H), 10.13 (s, 1H) IR: (KBr): cm ^-1 3616,3340,2956,1641,1515,1434,828

Synthesis Example 2 4-hydroxy-N- (3-hydroxyphenyl) benzamide (Compound 2) was obtained in the same manner as in Synthesis Example 1 (3).
5%). mp.230-231 ° C NMR: (DMSO-d ₆ ): δ; ppm 6.87 (d, 1H, J = 8Hz), 6.93 (d, 2H, J = 8Hz), 7.38 (t, 1H, J = 8H)
z), 7.64 (d, 1H, J = 8Hz), 7.76 (s, 1H), 7.86 (d, 1H, J = 8Hz), 8.
00 (d, 1H, J = 8Hz), 10.00 (br.s, 2H), 10.13 (s, 1H)

Synthesis Example 3 In the same manner as in Synthesis Example 1, 4-vidroxy-N- (4-hydroxyphenyl) benzamide (Compound 3) was obtained (6)
1%). mp.276.1 ° C (automatic melting point measurement) NMR: (DMSO-d ₆ ): δ; ppm 6.71 (d, 2H, J = 9Hz), 6.82 (d, 2H, J = 8Hz), 7.43 (d, 2H, J = 9H
z), 7.81 (d, 2H, J = 8Hz), 9.17 (s, 1H), 9.74 (s, 1H), 10.00 (s,
1H)

Synthesis Example 4 3,5-Di-t-butyl-4-hydroxybenzoic acid (6.26 g, 25.0 mmol) and p-aminophenol (2.73 g, 25.0 mmol) were mixed with ethyl acetate-dimethylformamide. (4: 1) dissolved in a mixed solvent (60 ml), and N, N ¹ -dicyclohexylcarbodiimide (5.16 g, 25.0 mmol) dissolved in ethyl acetate (20 ml) with stirring at 0 ° C. Was added. After 1 hour, the temperature was returned to room temperature and stirring was continued for 2 hours to complete the reaction. The reaction solution was filtered to remove urea and then extracted with chloroform. The organic layer was washed successively with 3% hydrochloric acid, aqueous sodium hydrogen carbonate solution and saturated brine, and concentrated under reduced pressure. The residue was dissolved in methanol-ether, free urea was filtered off, the solution was concentrated again, and recrystallized with a mixed solvent of ethyl acetate-ether-n-hexane. -T-butyl-4-hydroxy-N
-(4-hydroxyphenyl) benzamide (5.18
g, 61%) (compound 4) was obtained. mp.237-241 ° C NMR: (DMSO-d ₆ ): δ; ppm 1.43 (s, 18H), 6.73 (d, 2H, J = 9Hz), 7.45 (d, 2H, J = 9Hz), 7.50
(br.s, 1H), 7.65 (s, 2H), 9.18 (br.s, 1H), 9.80 (s, 1H) IR: (KBr): cm ^-1 3616,3340,2956,1641,1515,1430 , 828

Synthesis Example 5 3,5-Di-t-butyl-4-hydroxy-N- (3-hydroxyphenyl) benzamide (Compound 5) was obtained in the same manner as in Synthesis Example 4 (20%). mp.237-241 ° C NMR: (DMSO-d ₆ ): δ; ppm 1.44 (s, 18H), 6.42-6.51 (m, 1H), 7.13-7.04 (m, 2H), 7.29
(s, 1H), 7.47 (br.s, 1H), 7.64 (s, 2H), 9.33 (br.s, 1H), 9.90
(s, 1H)

Synthesis Example 6 In the same manner as in Synthesis Example 4, 3,5-di-t-butyl-4-hydroxy-N- (2-hydroxyphenyl) benzamide (Compound 6) was obtained (50%). mp.237-241 ° C NMR: (DMSO-d ₆ ): δ; ppm 1.44 (s, 18H), 6.79-7.06 (m, 2H), 7.00 (d, 1H, J = 8Hz), 7.53
(br.s, 1H), 7.64 (d, 1H, J = 8Hz), 7.72 (s, 2H), 9.47 (s, 1H),
9.67 (br.s, 1H) IR: (KBr): cm ^-1 3620,3334,2962,1638,1605,1533,1455,1368,1239,750

Example 1 An ethanol solution containing 1% by weight of each of the compounds 1 to 6 obtained in Synthesis Examples 1 to 6 was prepared and subjected to the following tests.

(Test 1) Wrinkle formation inhibition test by hairless mouse: 80 μl of an ethanol solution of anilide benzoic acid (1) was applied to the back of a hairless mouse (HR / ICR, 6 weeks old at the start of the experiment). After 2 hours, wipe off the benzoyl anilides (1) on the surface of the skin with ethanol, and use a health line lamp (TOSHIBA, SE
20) was used, and UVB light irradiation was carried out by adjusting the irradiation amount once to 1 MED or less, and irradiation was carried out 5 times a week for 8 weeks. UV irradiation energy amount
-Radiometer (TOKYO OPTICAL
UVR-305 / 365D manufactured by the company) was used for the measurement.
Further, as a control, a sample coated with ethanol alone was coated in the same manner as the sample. After the test was completed, the frequency of the wrinkles formed was visually evaluated according to the following criteria (wrinkle index). Table 1 shows the results.

Wrinkle index: 0: No wrinkles formed 1: Wrinkles formed slightly 2: Wrinkles formed in a small amount 3: Wrinkles slightly formed 4: Wrinkles formed strongly

(Test 2) Analysis of wrinkles: In order to analyze the wrinkles formed in Test 1 in detail, a hydrophilic Exaflex hydrophilic vinyl silicone image-forming agent was used for each mouse.
Skin replicas were collected from three locations in a circle with a diameter of 1 cm. This replica was irradiated with light from a 30 ° direction in a horizontal state, and the ratio of shadows formed by wrinkles was obtained as an area ratio using an image analyzer. The results are also shown in Table 1.

[0033]

[Table 1]

(Test 3) Effect of UVB pigmentation on the back of the brown guinea pig: The back hair of the brown guinea pig is carefully shaved with a hair clipper and a shaver, and then it is divided into eight 1.5 cm squares. Apply an evaluation sample (100 mM, 20 μl) to each site,
2 hours later, wipe the applied sample with ethanol,
Ultraviolet rays in the UVB region are irradiated at twice the minimum erythema dose (MED). After UV irradiation, re-evaluate sample (100 mM, 20μ
l) is applied. This operation is repeated for 3 days. After that, only the sample (100 mM, 10 μl) was applied continuously for 1 week,
The amount of pigmentation was examined after 2 weeks. As a control, ethanol was applied instead of the sample. The evaluation was carried out by measuring with a color difference meter, the L ^* value was calculated from the obtained Munsell value, and the value obtained by subtracting the L ^* value before UVB irradiation from the L ^* value 2 weeks after UVB irradiation as shown below (ΔL ^* ) Was calculated and the degree of pigmentation was compared. The larger the -ΔL ^* value, the stronger the degree of pigmentation.

[0035]

[Number 1] ΔL ^* = after UVB irradiation L ^* value -UVB before irradiation of the L ^* value

The results are shown in Table 2.

[0037]

[Table 2]

From the above results, it was shown that this sample has an excellent pigmentation inhibiting effect.

Hereinafter, in Examples 2 to 4, the cosmetics having the respective compositions were mixed and manufactured by a conventional method.

[0040]

Table 3 Example 2. Cream: Compound 6 0.2 (wt%) Cholesterol 0.5 Cholesterol isostearate 1 Polyether-modified silicone 1.5 Cyclic silicone 20 Methylphenylpolysiloxane 2 Methylpolysiloxane 2 Magnesium sulfate 0.5 55% Ethanol 5 Carboxymethyl Chitin 0.5 Allantoin 1 Fragrance, pigment Micro purified water Balance meter 100.0

[0041]

Table 4 Example 3. Skin lotion: Compound 6 2 (wt%) Glycerin monostearate 1 Ethanol 15 Propylene glycol 4 Isopropyl palmitate 3 Lanolin 1 Methyl paraoxybenzoate 0.1 Perfume, pigment Micro purified water 73.9 Total 100.0

[0042]

Table 5 Example 4. Packing agent: Compound 64 (% by weight) Polyvinyl alcohol 20 Glycerin 5 Ethanol 16 Perfume, dye Micro purified water 55 Total 100.0

 ─────────────────────────────────────────────────── ─── Continued Front Page (72) Inventor Hiroyuki Osu 2606-6 Akabane, Kai-cho, Haga-gun, Tochigi Prefecture (72) Inventor Ichiro Tokimitsu 89-28 Takebayashi-cho, Utsunomiya-shi, Tochigi Prefecture

Claims (1)

[Claims] 1. The following general formula (1): [In the formula, R ¹ represents a hydrogen atom or a t-butyl group, and R ²
Represents a hydrogen atom or an alkyl or acyl group having 1 to 5 carbon atoms], and a skin cosmetic containing the anilide benzoate or a salt thereof.