JPH06329516A - Cosmetic - Google Patents

Abstract

PURPOSE:To provide a safe cosmetic containing anacardic acid obtained from a cashew nut shell oil, etc., high in a beautifully whitening effect, inhibiting the activity of hyaluronidase, effective for taking care of skin roughness, etc., and large in effects to maintain the gloss and tension of skin. CONSTITUTION:A cosmetic containing the derivative of anacardic acid. Especially a compound of formula I [A is COOH, COOCH3, CHO; B is CH3O, OH; R is group of formula II, formula III or formula IV (CmHn, CPHq are saturated or unsaturated hydrocarbon)], more especially the compound wherein the carbon atom number of R is 15, is preferable as the anacardic acid derivative. The anacardic acid derivative is obtained e.g. from an anacardic acid monoene, i.e., 6-[8(Z)-pentadecamonoenyl]salicylic acid [the 8(Z) exhibits the position of the enyl group] as a starting raw material, the compound being contained in a cashew nut oil having been low in utilization value. The anacardic acid derivative has a beautifully whitening action, a hyaluronibase activity-inhibiting action and further an active oxygen-reducing action. The cosmetic is high in the concentration of the active ingredient, little in adverse effects, and safe.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a cosmetic which has a high whitening effect, inhibits the activity of hyaluronidase, and is effective against rough skin.

[0002]

BACKGROUND OF THE INVENTION Anacardic acid is obtained from cashew nut shell liquid and the like. Regarding cashew nut shell liquid, the present inventors have disclosed that as an antioxidant in JP-A-3-217484,
A patent application was filed in JP-A-3-240718 as an external skin preparation for acne treatment and in JP-A-3-240721 as an oral composition. Further, as a whitening cosmetic, the present inventors have applied for a patent in Japanese Patent Application Laid-Open No. 4-89419 with cardol as an active ingredient. However, cashew nut shell liquid has a problem that the content of active ingredients is low.

[0003]

DISCLOSURE OF THE INVENTION The object of the present invention is to apply a pure ingredient which is safe to be applied to the skin, has a large whitening effect and inhibits the activity of hyaluronidase, and is effective for rough skin, to the cashew nut shell. It is to provide a cosmetic raw material having a high concentration of an active ingredient by being obtained synthetically without being purified from oil.

[0004]

[Means for Solving the Problems] The present inventors have already found and disclosed that the ingredient of cashew nut shell liquid is effective as a raw material for cosmetics, but further increase this effectiveness and eliminate side effects due to impurities. Therefore, as a result of producing various derivatives, highly effective substances were obtained and the present invention was completed. Therefore, it is not always necessary to purify from cashew nut shell oil, and the structure of the active ingredient is known. Therefore, whichever method is used, if the substance constituting the present invention is obtained as a result, no problem occurs. It is effective.

That is, the present invention provides (1) a cosmetic containing a derivative of anacardic acid.

(2) A derivative of anacardic acid has a structure represented by the following general formula, wherein A is a COOH group, a COOCH ₃ group,
Anacardo, which is any one group of CHO groups, B is any one group of CH ₃ O groups and OH groups, and R is any one group of R ₁ , R ₂ and R ₃ shown below. Cosmetics containing an acid derivative.

[Chemical 2]

(3) A cosmetic containing the derivative of anacardic acid according to the above (2), wherein R has 15 carbon atoms.

In the present invention, among cashew nut shell liquids having a low utility value, monoene of anacardic acid 6- [8 (Z) -pentadecamonoenyl] which is the main component is used.
-A salicylic acid {8 (Z) represents the position of an enyl group} was used as a starting material, and this substance was combined with a known synthesis method for each method itself to prepare a derivative of anacardic acid.

As described below, this substance has been proved to have a skin whitening effect, a hyaluronidase activity suppressing effect, and an active oxygen suppressing effect. Therefore, other cosmetic raw materials such as squalane, liquid oil such as jojoba oil, beeswax, cetyl alcohol. Cosmetics of various dosage forms can be prepared by adding solid oils such as, various active agents, humectants such as glycerin and 1,3 butylene glycol, and various agents. For example, a lotion, a cream, a milky lotion, a pack, or the like may be used depending on the purpose.

The effect of the anacardic acid derivative of the present invention is
First, there is a whitening effect on the skin, and a tyrosinase activity inhibiting effect is recognized as described below. Secondly, it has an activity of suppressing hyaluronidase activity. Hyaluronidase is an enzyme that is widely distributed in the living body and is also present in the skin. As its name implies, it decomposes hyaluronic acid. Hyaluronic acid is a linear polymeric polysaccharide in which β-D-N-acetylglucosamine and β-D-glucuronic acid are linked alternately. It is a glycosaminoglucan that exists widely in connective tissues of mammals along with chondroitin sulfate. It is a kind.

As a function of hyaluronic acid in connective tissue, water is retained in the intercellular spaces, and a jelly-like matrix is formed in the tissue to retain cells, and the lubricity and flexibility of the skin are maintained. It is believed to prevent external forces (mechanical disorders) and bacterial infections. It is said that hyaluronic acid in the skin decreases with age, resulting in aging such as wrinkles and roughness. Therefore, suppressing the activity of hyaluronidase, which decomposes this, contributes to the stability of hyaluronic acid used in the formulation and the stability of hyaluronic acid in the formulation after application to the skin and hyaluronic acid present in the skin. It is thought that.

Thirdly, it has an effect of suppressing active oxygen. There is oxygen in the air, and without it, living things (except anaerobic ones) cannot exist. However, oxygen becomes active oxygen under the influence of ultraviolet rays and enzymes. Active oxygen oxidizes fatty acids and produces peroxides. It also oxidizes and damages the phospholipids of biological membranes in the body. Furthermore, it is said that the generated peroxide and active oxygen damage DNA and promote aging. This active oxygen also influences the mechanism of making melanin from tyrosine and is also involved in the blackening of the skin. Suppressing this active oxygen is an important factor for the skin, in other words, an important factor required for cosmetics. The present invention also has this active oxygen suppressing effect.

[0013]

[Manufacturing Example] A manufacturing example which is an actual method of use will be described below, but the present invention is not limited to this manufacturing example.

(Production Example 1) 3- [8 (Z) -pentadecamonoenyl] -2-methoxycarbonylphenol 6- [8 (Z) -pentadecamonoenyl] -salicylic acid 1 was placed in an Erlenmeyer flask equipped with a reflux condenser. 0.0g and N, N-
Dimethylformamide Dimethyl acetal (CH ₃ ) ₂ N
CH (OCH ₃ ) ₂ (1.05 g) and tetrahydrofuran (4.0 ml) were added, and the mixture was heated under reflux in an oil bath at 65 to 70 ° C. for 8 hours with stirring on a magnetic stirrer. Then, the mixture was extracted with ethyl acetate, washed with dilute hydrochloric acid, and the crude reaction product obtained by the usual operation was purified by silica gel column chromatography with ethyl acetate to give 3- [8
(Z) -Pentadecamonoenyl] -2-methoxycarbonylphenol was obtained.

0.6 g of the purified product was added to calcium chloride C
The mixture was placed in an Erlenmeyer flask equipped with an aCl ₂ tube, 0.53 g of meta-chloroperbenzoic acid and 6 ml of anhydrous ether were placed, and the mixture was allowed to stand in the refrigerator (2 ° C.) for 1 week. Then, the obtained crude reaction product was purified by silica gel column chromatography using hexane: ethyl acetate = 65: 35 and ethyl acetate 100%. The yield was 79.6%.

(Production Example 2) 3- [8,9-epoxypentadecayl] salicyl alcohol Lithium aluminum hydride LiAlH ₄ 0.85 in a four-necked flask equipped with a stirrer, a reflux condenser and a dropping funnel.
g, cooled, suspended in 25 ml of anhydrous ether,
While keeping the internal temperature below 4 ° C, 5.0 g of 6- [8 (Z) -pentadecamonoenyl] -salicylic acid and anhydrous ether 1
5 ml of the mixed solution was added dropwise over 1 hour. Then, it heated and refluxed for 4 hours on an oil bath (35-45 degreeC). After cooling
100 ml of ethyl acetate was gradually added to decompose unreacted lithium, remove lithium powder by suction filtration, and distill off the solvent.

The crude reaction product obtained was then purified by column chromatography on silica gel using ether. (6- [8 (Z) -pentadecamonoenyl] -salicyl alcohol) 0.6 g of the purified product was placed in an Erlenmeyer flask equipped with a CaCl ₂ tube of calcium chloride, 0.53 g of meta-chloroperbenzoic acid and 6 ml of anhydrous ether. Put in the refrigerator (2 ℃)
Left for 1 week. Then, the obtained crude reaction product was purified by silica gel column chromatography using hexane: ethyl acetate = 65: 35 and ethyl acetate 100%. The yield was 64.5%.

(Production Example 3) 6- [8,9-dihydroxypentadecayl] salicylic acid 6- [8 (Z) -pentadecamonoenyl-salicylic acid 0.6 g was placed in an Erlenmeyer flask equipped with a calcium chloride CaCl ₂ tube. Then, 0.53 g of meta-chloroperbenzoic acid and 6 ml of anhydrous ether were added, and the mixture was allowed to stand in a refrigerator (2 ° C) for 1 week. Then, the obtained crude reaction product was subjected to column chromatography on silica gel with hexane: ethyl acetate = 65: 3.
Purified with 5 and 100% ethyl acetate. (6-
[8,9-Epoxypentadecayl] salicylic acid) 0.4 g of this was placed in an Erlenmeyer flask equipped with a reflux condenser, 40 ml of acetone, 20 ml of water, and 1.2 ml of formic acid were placed in the magnetic stirrer for 4 hours at room temperature. It was stirred.

Then, the solvent was distilled off, and the mixture was extracted with ethyl acetate. The obtained crude reaction product and 0.1N sodium hydroxide methanol solution were put in a 300 ml receiver and placed on an oil bath (7
The mixture was heated under reflux at 0 to 75 ° C for 1 hour and 30 minutes. After cooling
The crude reaction product was extracted with ethyl acetate and operated in the usual manner to purify the crude reaction product by silica gel column chromatography using hexane: ethyl acetate = 65: 35 and ethyl acetate 100%. The yield was 39.1%.

(Production Example 4) 6- [8,9-epoxypentadecayl] -2-methoxybenzoic acid 6- [8 (Z) was added to a four-necked flask equipped with a stirrer, a reflux condenser and a dropping funnel. -Pentadecamonoenyl] -salicylic acid (1.0 g) and 10% aqueous sodium hydroxide solution (4 ml) were added and dimethylsulfate (0.74 g) was added to 30 while maintaining the internal temperature at 0 ° C.
The mixture was added dropwise over minutes, and heated under reflux on an oil bath (100 to 105 ° C.) for 30 minutes. After cooling, the mixture was extracted with ethyl acetate, and the crude reaction product obtained by the usual operation was purified by silica gel column chromatography using ether. (6-
[8 (Z) -pentadecamonoenyl] -2-methoxybenzoic acid)

0.6 g of the purified product was added to calcium chloride C
The mixture was placed in an Erlenmeyer flask equipped with an aCl ₂ tube, 0.53 g of meta-chloroperbenzoic acid and 6 ml of anhydrous ether were placed, and the mixture was allowed to stand in the refrigerator (2 ° C.) for 1 week. Then, the obtained crude reaction product was purified by silica gel column chromatography using hexane: ethyl acetate = 65: 35 and ethyl acetate 100%. The yield was 89.7%.

(Production Example 5) 6- [8,9-dihydroxypentadecayl] -2-methoxybenzoic acid 6- [8,9-epoxypentadecayl] -2-methoxybenzoic acid obtained in Production Example 4 0.4 g was placed in an Erlenmeyer flask equipped with a reflux condenser, 40 ml of acetone, 20 ml of water,
Formic acid (1.2 ml) was added, and the mixture was stirred on a magnetic stirrer at room temperature for 4 hours.

Then, the solvent was distilled off and the mixture was extracted with ethyl acetate. The obtained crude reaction product and 0.1N sodium hydroxide methanol solution were put in a receiver and placed on an oil bath (70-75).
The mixture was heated to reflux for 1 hour and 30 minutes. After cooling, the mixture was extracted with ethyl acetate, and the crude reaction product obtained by the usual operation was purified by silica gel column chromatography using hexane: ethyl acetate = 65: 35 and ethyl acetate 100%. The yield was 63.1%.

(Production Example 6) 6- [8,9-epoxypentadecayl] -salicylaldehyde 9.02 g of pyridinium dichromate and 136 ml of acetone were added to a four-necked flask equipped with a stirrer and a reflux condenser. While maintaining the internal temperature at 0 ° C., 4.51 g of 6- [8 (Z) -pentadecamonoenyl] -salicyl alcohol obtained in the production process of Production Example 2 was added and stirred for 4 hours. Then, the obtained reaction mixture was purified by silica gel column chromatography by sequentially using methanol, acetone and ethyl acetate to obtain 6- [8 (Z) -pentadecamonoenyl] -salicylaldehyde.

0.6 g of this purified 6- [8 (Z) pentadecamonoenyl] -salicyl aldehyde was placed in an Erlenmeyer flask equipped with a calcium chloride CaCl ₂ tube, and meta-
Chloroperbenzoic acid (0.53 g) and anhydrous ether (6 ml) were added, and the mixture was allowed to stand in the refrigerator (2 ° C) for 1 week. Then, the obtained crude reaction product was subjected to column chromatography on silica gel with hexane: ethyl acetate = 65: 35 and ethyl acetate 10
Purified with 0%. The yield was 12.9%.

(Production Example 7) 6- [8,9-epoxypentadecayl] -2-methoxybenzaldehyde Obtained by the production process of Production Example 6 in a four-necked flask equipped with a stirrer, a reflux condenser and a dropping funnel. 6- [8 (Z) -pentadecamonoenyl] -salicylaldehyde and 1.0 ml of 10% aqueous sodium hydroxide solution were added and 0.74 g of dimethylsulfate was added dropwise over 30 minutes while keeping the internal temperature at 0 ° C. It heated and refluxed for 30 minutes on the bath (100-105 degreeC). After cooling, the mixture was extracted with ethyl acetate, and the crude reaction product obtained by the usual operation was purified by silica gel column chromatography using ether. (6- [8
(Z) -Pentadecamonoenyl] -2-methoxybenzaldehyde)

0.6 g of the purified product was added to calcium chloride C
The mixture was placed in an Erlenmeyer flask equipped with an aCl ₂ tube, 0.53 g of meta-chloroperbenzoic acid and 6 ml of anhydrous ether were placed, and the mixture was allowed to stand in the refrigerator (2 ° C.) for 1 week. Then, the obtained crude reaction product was purified by silica gel column chromatography using hexane: ethyl acetate = 65: 35 and ethyl acetate 100%. The yield was 82.5%.

Example-1 Lotion Olive Oil 0.5 3- [8 (Z) -pentadecamonoenyl] -2-methoxycarbenylphenol 0.5 from Production Example 1 Polyoxyethylene (20E.O.) sorbitan mono Stearate 2.0 Polyoxyethylene (60 E.O.) Hydrogenated castor oil 2.0 Ethanol 10.0 1.0% sodium hyaluronate aqueous solution 5.0 Purified water 80.0

Example-2 Cream A Squalane 20.5 Olive Oil 2.0 Mink Oil 1.0 Jojoba Oil 5.0 Beeswax 5.0 Cetostearyl Alcohol 2.0 Glycerin Monostearate 1.0 Sorbitan Monostearate 2.0 3- [8,9-Epoxy pentadecayl] salicyl alcohol 0.5 B Purified water 47.9 Polyoxyethylene (20 E.O.) sorbitan monostearate 2.0 Polyoxyethylene 60 E.O.) Hydrogenated castor oil 1.0 Glycerin 5.0 1.0% sodium hyaluronate aqueous solution 5.0 Methyl paraoxybenzoate 0.1 A and B are weighed and heated to 70 ° C. After gradually adding A while stirring, 30 while slowly stirring
Cooled to ° C.

The example 3 is the same as the example 3 of the production example 1 of the example-1.
[8 (Z) -Pentadecamonoenyl] -2-methoxycarbonylphenol prepared in place of 6- [8,9-dihydroxypentadecyl] salicylic acid of Production Example 3.

Example-4 is 3-of Production Example 2 of Example-2.
[8,9-epoxypentadecayl] salicyl alcohol was prepared by replacing 6- [8,9-epoxypentadecayl] -2-methoxybenzoic acid of Production Example 4.

Example-5 is No. 3 of Production Example 1 of Example-1.
[8 (Z) -Pentadecamonoenyl] -2-methoxycarbonylphenol was prepared by replacing 6- [8,9-dihydroxypentadecayl] -2-methoxybenzoic acid of Production Example 5.

Example 6 is 3 of Production Example 2 of Example-2.
[8,9-epoxypentadecayl] salicyl alcohol was prepared by replacing 6- [8,9-epoxypentadecayl] -salicylaldehyde of Preparation Example 6.

Example-7 is No. 3 of Production Example 1 of Example-1.
[8 (Z) -pentadecamonoenyl] -2-methoxycarbonylphenol was prepared by replacing 6- [8,9 epoxypentadecayl] -2-methoxybenzaldehyde in Production Example 7.

[Tyrosinase activity inhibition test] (Test method) Mcllvaln buffer solution 1.8
ml, 1.0 ml of 0.05% Dopa solution, and 0.1 ml of the 15 mM dimethyl sulfoxide solution of Preparation Example were placed in a screw vial and left in a constant temperature water bath at 25 ° C. for 5 minutes or more. Tyrosinase solution (manufactured by Sigma, mushroom-derived, diluted 2 minutes after the addition of tyrosinase by the following measurement so that the absorbance of the control becomes 0.3 to 0.5)
0.1 ml was added, and the mixture was stirred, transferred to a cell, and the absorbance at 475 nm was measured 30 seconds after the addition of tyrosinase and at 15 second intervals while being kept at 25 ° C. As a control, 0.1 ml of dimethyl sulfoxide was added instead of the above sample solution and the same measurement was performed. In this test, the final concentration of the sample is 0.5m
It becomes M. (Calculation formula) Tyrosinase activity inhibition rate (%) = (B−A) / B × 10
0 where A: slope of absorbance of sample specimen B: slope of absorbance of control The results are shown in Table 1.

[0036]

[Table 1]

[Hyaluronidase activity inhibition test] (Test method) 0.4% sodium hyaluronate 0.1M
(PH 6.0) Weigh 6 g of phosphate buffer solution,
After standing in a constant temperature water bath at 7 ° C for 5 minutes, 0.1 ml of the 15 mM dimethylsulfoxide solution of Production Example and 0.9 ml of purified water were added and stirred, and 0.01% hyaluronidase (manufactured by Sigma, beef testis, type I-S). 1 ml of 0.1 M (pH 6.0) phosphate buffer solution was added and immediately stirred, and 6 ml was placed in an Ostwald viscometer placed in a constant temperature water bath at 37 ° C. The viscosity was measured after 1 minute, 5 minutes, 10 minutes, 20 minutes, and 40 minutes. As a control, instead of the above sample solution, 0.1 ml of a dimethylsulfoxide solution and 0.9 ml of purified water were added to pure water, and the same measurement was performed. The final concentration of the sample in this test is 0.18
It becomes 75 mM. The results are shown in Tables 2 to 5 as indexes, with the viscosity after 1 minute being 100.

[0038]

[Table 2]

[0039]

[Table 3]

[0040]

[Table 4]

[0041]

[Table 5]

[Effect of Active Oxygen Suppression Test] There are various methods for measuring the effect of suppressing active oxygen, but this time an experiment was carried out using SOD Test Wako of Wako Pure Chemical Industries. Use the coloring reagent 1.
0 ml of a sample (0.1 ml of 15 mM dimethylsulfoxide solution in the preparation example) was taken and kept at 37 ° C. to a constant temperature, 1.0 ml of enzyme solution was added and stirred, and after leaving at 37 ° C. for 20 minutes, the reaction stop solution was added to 2 ml. 0.0 ml was added and the absorbance was measured at 560 nm. In this test, the final concentration of the sample is 0.375m
It becomes M. The results are shown in Table 6.

[0043]

[Table 6]

[Use Test] Six women were divided into left and right faces, one of which was used as an example and the other of which was used as a comparative example. They were used once or more daily, and a questionnaire was given after 3 months.
The comparative examples are those obtained by excluding the production example 1 from the example 1 (comparative example 1) and excluding the production example 2 from the example 2 (comparative example 2). In addition, 24 people were divided into 4 groups and experimented using the samples in Table 7.

[0045]

[Table 7]

The judgment criteria are as follows, and the results of the questionnaires are totaled and the total value is shown in Table 8 as an evaluation. Example is very good 3 Example is considerably good 2 Example is slightly good 1 No difference 0 Comparative example is good −1 Comparative example is good −2 Comparative example Is very good -3

[0047]

[Table 8]

[0048]

The cosmetics containing the anacardic acid derivative of the present invention have a high whitening effect, inhibit the activity of hyaluronidase, effectively retain hyaluronic acid on the skin for a long time, and further suppress the production of active oxygen. To prevent rough skin,
It has a great effect on keeping the skin shiny. Since it is originally contained in a natural product and is purified or synthesized so as not to contain impurities that cause side effects, it is a cosmetic that has a high concentration of the active ingredient and is applied to the skin with few side effects and is safe.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical display location C07C 45/57 7188-4H 47/56 7188-4H 65/28 8930-4H 69/92 9279-4H C07D 303/32 303/38 303/40 (72) Inventor Yoshito Fujiwara 13-5 Hase-cho, Kure-shi, Hiroshima (72) Inventor Masato Nomura 260-38 Maruyama, Kurose-cho, Kamo-gun, Hiroshima

Claims (3)

[Claims] 1. A cosmetic containing a derivative of anacardic acid. 2. A derivative of anacardic acid having a structure represented by the following general formula, wherein A is a COOH group, a COOCH ₃ group, or CHO.
Anacardic acid, which is any one group of groups, B is any one group of CH ₃ O group and OH group, and R is any one group of R ₁ , R ₂ and R ₃ shown below. A cosmetic containing a derivative of. [Chemical 1] 3. A cosmetic containing the anacardic acid derivative according to claim 2, wherein R has 15 carbon atoms.