JP3150783B2 - External preparation for skin - Google Patents

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 contains a cyclohexanecarboxylic acid derivative as an active ingredient and is excellent in skin whitening effect, skin roughness prevention and improvement effects.

[0002]

2. Description of the Related Art Although there are some unclear points about the mechanism of the occurrence of skin spots and the like, melanin pigments are generally formed due to hormonal abnormalities and stimulation of ultraviolet rays from sunlight. It is believed to be abnormally deposited within. Treatment of such spots and bruises includes substances that suppress the production of melanin, such as a method of administering a large amount of vitamin C, a method of injecting glutathione, etc., or kojic acid,
A method of applying cysteine or the like in the form of an ointment, cream, lotion, or the like, and topically applying the composition is employed. In the United States and Europe, hydroquinone preparations are used as pharmaceuticals.

[0003]

However, these compounds, except for hydroquinone, exhibit very slow effects, so that the whitening effect is not sufficient, while hydroquinone has been recognized to be effective. Due to its sensitizing properties, its use is generally restricted.

In view of such circumstances, the present inventors have conducted intensive studies and as a result, have found that a specific cyclohexanecarboxylic acid derivative exerts a whitening effect more than hydroquinone.
Furthermore, the present inventors have recognized that they have the effect of preventing and improving rough skin, and have completed the present invention.

[0005]

That is, the present invention is an external preparation for skin characterized by containing a cyclohexanecarboxylic acid derivative represented by the following general formula (4).

[0006]

Embedded image Wherein A is phenyl, pyridyl, p-isopropenylphenyl, or

[0007]

Embedded image (Where X ₁ represents a hydrogen atom, a hydroxyl group or a methoxy group, X ₂ represents a hydrogen atom, a hydroxyl group or a methoxy group,
₃ is a hydroxyl group, a methoxy group, a halogen atom, a nitro group, a trifluoromethyl group, a carboxyl group or a general formula 6
Respectively)

[0008]

Embedded image , R represents a hydrogen atom, Na or an alkyl group having 1 to 4 carbon atoms, and R ₁ represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, respectively]

Hereinafter, the configuration of the present invention will be described in detail. A in the general formula 4 used in the present invention will be described more specifically. As the pyridyl group of A, there can be mentioned a 2-pyridyl group, a 3-pyridyl group and a 4-pyridyl group, and X ₃
Examples of the halogen atom include chlorine, bromine, iodine and fluorine.

The cyclohexanecarboxylic acid derivative according to the present invention is disclosed in, for example, JP-B-63-12055 and JP-B-63-4
No. 6736, JP-A-57-116035, JP-A-57-140
The compound can be easily synthesized by the method described in, for example, JP-A-714.

To give a concrete example of a substance name, trans-
4-benzylideneaminomethylcyclohexanecarboxylic acid, trans-4- (2'-nitrobenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4-
(3'-nitrobenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (4'-nitrobenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (2'-hydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4 -(3 '
-Hydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (4'-hydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (2'-methoxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (3 ′
-Methoxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (4'-methoxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (3'-carboxy-4'-hydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans -4- (3 ', 4', 5'-trimethoxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (3 ', 4', 5'-trihydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4 -(3 ', 4'-dimethoxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4-
(2 ', 3'-dimethoxybenzylideneaminomethyl)
Cyclohexanecarboxylic acid, trans-4- (2 ′,
4'-dimethoxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (2 ', 5'-dimethoxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (3', 5'-dimethoxybenzylideneaminomethyl) cyclohexanecarboxylic acid Acid, trans-4- (3 ', 4'-dihydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-
4- (2 ', 3'-dihydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4-
(2 ', 4'-dihydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4-
(2 ', 5'-dihydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4-
(3 ', 5'-dihydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (4'
-Chlorobenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (2'-chlorobenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-
4- (3'-trifluoromethylbenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4-
(3'-pyridylmethylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (4'-pyridylmethylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (4'-isopropenylbenzylideneaminomethyl) cyclohexanecarboxylic acid, Trans-4-
(3 ', 4'-dihydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid ethyl ester and the like.

The topical skin preparation of the present invention comprises at least one cyclohexanecarboxylic acid derivative obtained as described above.
And more than 0.001 of the total amount of skin external preparation
It is 20% by weight, preferably 0.01 to 7% by weight. If the amount is less than 0.001% by weight, the skin whitening effect and the skin roughening prevention and improvement effects are poor.

The external preparation for skin of the present invention contains, in addition to the above-mentioned essential components, other components usually used in external preparations for skin such as cosmetics and pharmaceuticals, such as oils, ultraviolet absorbers, antioxidants, and surfactants. , Moisturizers, fragrances, water, alcohols, thickeners, coloring materials, skin nutritional agents (tocopherol acetate, pantothenyl ethyl ether, glycyrrhizinate) and the like can be appropriately compounded as necessary. .

[0014]

Next, the present invention will be described in more detail by way of examples. The present invention is not limited by this. The compounding amount is% by weight. Prior to the examples, the effect test method and the evaluation method of the present invention will be described.

(1) Whitening Effect Test Test Method The day 5 of 50 subjects exposed to sunlight in summer for 4 hours (2 hours a day for 2 days) was exposed to 50 subjects. After the day, each sample was applied once in the morning and evening for 8 weeks. The panel was divided into 10 groups and divided into 5 groups, and the test was performed according to the following formulation.

Samples of Examples 1 to 3 and Comparative Examples 1 and 2 (alcohol phase) weight% 95% ethyl alcohol 25.0 polyoxyethylene (25 mol) hydrogenated castor oil ether 2.0 antioxidant / preservative proper amount perfume proper amount Table 1) 1.0 (aqueous phase) Glycerin 5.0 Sodium hexametaphosphate Appropriate amount Ion-exchanged water Residue (Preparation method) Prepare aqueous phase and alcohol phase and solubilize.

(Evaluation Method) The lightening effect after use was determined based on the following criteria. (Judgment) ：: When the ratio of the effective and effective of the subjects is 80% or more ○: The ratio of the effective and effective among the subjects is 50 to 8
0%: △: 30% to 5% of the test subjects showed significant and effective
0%: ×: The proportion of subjects who show excellent and effective is 30% or less

[0018]

[Table 1]

As is evident from Table 1, the effect of the embodiment after exposure to sunlight is greater in the example than in the comparative example, in which the deposition of excess melanin pigment is prevented and the blackening is prevented. Admitted.

(2) Test Method for Preventing and Improving the Roughness of Skin After washing the face twice a day in the morning and at night, an appropriate amount of the cosmetics of Examples 1 to 3 was applied to the left side of the face, and an appropriate amount of the cosmetic of Comparative Example 1 was applied to the right side of the face. This was done by applying for two weeks. The test was conducted by dividing the 30 female panels into 10 groups, each group comprising 10 groups. (Evaluation method) The effectiveness of three items (moisture of skin, firmness of skin, moisture of the next morning) was determined based on the following criteria. (Judgment) ：: When the ratio of the effective and effective of the subjects is 80% or more ○: The ratio of the effective and effective among the subjects is 50 to 8
0%: △: 30% to 5% of the test subjects showed significant and effective
0%: ×: The proportion of subjects who show excellent and effective is 30% or less

[0021]

[Table 2]

As is evident from Table 2, the effect of skin moisture, skin firmness, and the effect of moisture in the next morning was better in the example than in the comparative example.

Example 4 Cream Weight% Stearic Acid 5.0 Stearyl Alcohol 4.0 Isopropyl Myristate 18.0 Glycerin Monostearate 3.0 Propylene Glycol 10.0 Trans-4- (3 ′, 4 ′, 5′-Trimethoxybenzylideneaminomethyl) cyclohexanecarboxy Acid 20.0 Caustic potash 0.2 Sodium bisulfite 0.01 Preservatives Appropriate amount Perfume Appropriate amount Ion-exchanged water Residue (Production method) Add propylene glycol and caustic potash to ion-exchanged water, heat and maintain at 70 ° C (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is gradually added to the aqueous phase, and after the addition is completed, the temperature is maintained for a while to cause a reaction. Thereafter, the mixture is uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well.

Example 5 Cream wt% stearic acid 6.0 sorbitan monostearate 2.0 polyoxyethylene (20 mol) sorbitan monostearate 1.5 propylene glycol 10.0 trans-4- (3'-pyridylmethylideneaminomethyl) cyclohexanecarbone Acid 7.0 Glycerin trioctanoate 10.0 Squalene 5.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Perfume Appropriate amount Ion-exchanged water Residue (Preparation method) Add propylene glycol to ion-exchanged water, heat and maintain at 70 ° C (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is added to the water phase, pre-emulsified, homogenized with a homomixer, and cooled to 30 ° C. with good stirring.

Example 6 Cream% by weight stearyl alcohol 7.0 stearic acid 2.0 hydrogenated lanolin 2.0 squalane 5.0 2-octyldodecyl alcohol 6.0 polyoxyethylene (25 mol) cetyl alcohol ether 3.0 glycerin monostearate 2.0 propylene glycol 5.0 trans-4 -(4'-Isopropenylbenzylideneaminomethyl) cyclohexanecarboxylic acid 0.005 Fragrance Appropriate amount Sodium bisulfite 0.03 Ethyl paraben 0.3 Ion-exchanged water Residue (Preparation method) Add propylene glycol to ion-exchanged water, heat and maintain at 70 ° C (water phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is added to the water phase, pre-emulsified, homogenized with a homomixer, and cooled to 30 ° C. with good stirring.

Example 7 Emulsion Weight% Stearic Acid 2.5 Cetyl Alcohol 1.5 Vaseline 5.0 Liquid Paraffin 10.0 Polyoxyethylene (10 mole) Monooleate 2.0 Polyethylene Glycol 1500 3.0 Triethanolamine 1.0 trans-4- (3 ′, 4'-Dimethoxybenzylideneaminomethyl) cyclohexanecarboxylic acid 10.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Carboxyvinyl polymer 0.05 Perfume Appropriate amount Ion-exchange water Residue (Preparation method) Dissolve the carboxyvinyl polymer in a small amount of ion-exchange water (A phase). Polyethylene glycol 1500 and triethanolamine are added to the remaining ion-exchanged water, dissolved by heating, and maintained at 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is added to the water phase, pre-emulsification is performed, phase A is added, and the mixture is uniformly emulsified with a homomixer. After the emulsification, the mixture is cooled to 30 ° C. while stirring well.

Example 8 Emulsion Weight% (oil phase) Stearyl alcohol 1.5 Squalene 2.0 Vaseline 2.5 Deodorized liquid lanolin 1.5 Evening primrose oil 2.0 Isopropyl myristate 5.0 Glycerin monooleate 2.0 Polyoxyethylene (60 mol) hydrogenated castor oil 2.0 Tocopherol acetate 0.05 Ethyl paraben 0.2 butyl paraben 0.1 trans-4- (4'-chlorobenzylideneaminomethyl) cyclohexanecarboxylic acid 1.0 trans-4- (2'-methoxybenzylideneaminomethyl) cyclohexanecarboxylic acid 1.0 Fragrance Appropriate amount (aqueous phase) Sodium bisulfite 0.01 Glycerin 5.0 Sodium hyaluronate 0.01 Carboxyvinyl polymer 0.2 Potassium hydroxide 0.2 Purified water Residue (Preparation method) Dissolve the oil phase at 70 ° C. 70 ° C in the aqueous phase
And the oil phase is mixed with the aqueous phase, emulsified by an emulsifier, and then cooled to 30 ° C. by a heat exchanger.

Example 9 Jelly weight% 95% ethyl alcohol 10.0 dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl alcohol ether 2.0 carboxyvinyl polymer 1.0 caustic soda 0.15 L-arginine 0.1 trans-4- (2′-hydroxybenzylideneamino Methyl) cyclohexanecarboxylic acid 1.0 trans-4- (3'-trifluoromethylbenzylideneaminomethyl) cyclohexanecarboxylic acid 1.0 methyl paraben 0.2 perfume Appropriate amount Ion-exchanged water residue (Preparation method) Uniformly dissolve carboxyvinyl polymer in ion-exchanged water, Trans-4- in 95% ethanol
Dissolve (2'-hydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid, trans-4- (3'-trifluoromethylbenzylideneaminomethyl) cyclohexanecarboxylic acid, polyoxyethylene (50 mol) oleyl alcohol ether and add to aqueous phase I do. Then, after adding other components, the mixture is neutralized with caustic soda and L-arginine to increase the viscosity.

Example 10 Serum Weight% (A phase) Ethanol (95%) 10.0 Polyoxyethylene (20 mol) Octyldodecanol 1.0 Methyl paraben 0.15 Pantothenyl ethyl ether 0.1 Trans-4- (3'-carboxy-4 ' -Hydroxybenzylidene aminomethyl) cyclohexanecarboxylic acid 0.05 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 Purified water Residue (Production method) A phase and C phase are uniform In phase C and A in phase C
Add phases and solubilize. Next, after the phase B is added, filling is performed.

Example 11 pack weight% (phase A) dipropylene glycol 5.0 polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (phase B) trans-4- (2'-nitrobenzylideneaminomethyl) cyclohexanecarboxylic acid 1.0 trans -4- (3 ', 4'-dihydroxybenzylideneaminomethyl) cyclohexanecarboxylic acid ethyl ester 1.0 olive oil 5.0 tocophenol acetate 0.2 ethylparaben 0.2 fragrance 0.2 (phase C) sodium bisulfite 0.03 polyvinyl alcohol (degree of saponification 90, degree of polymerization 2000) 13.0 Ethanol 7.0 Purified water Residue (Production method) A phase, B phase, and C phase are each dissolved uniformly, and A
Add phase B to phase and solubilize. Then, after adding this to phase C, filling is performed.

The skin external preparations obtained according to the present invention were all subjected to the whitening effect tests and the prevention of rough skin conducted in Examples 1 to 3,
The effect was recognized in the improvement effect test.

[0032]

The external preparation for skin containing the cyclohexanecarboxylic acid derivative according to the present invention is a novel external preparation for skin having both skin whitening effect and prevention and improvement of skin roughness.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI A61K 31/216 A61K 31/216 31/44 31/44 A61P 17/00 A61P 17/00 (72) Inventor Yuki Yamase Yokohama, Kanagawa 1050 Nippa-cho, Kohoku-ku, Shizuido 1st Research Center, Shiseido Co., Ltd. (72) Inventor Naoe Akiyama 1050 Nippa-cho, Kohoku-ku, Yokohama, Kanagawa, Japan 1st Research Center at Shiseido Co., Ltd. 1050 Nippa-cho, Kohoku-ku, Yokohama-shi Shiseido Co., Ltd. 1st Research Center Investigator Ikuji Oya (56) References JP-A-57-2256 (JP, A) JP-A-57-59848 (JP, A) (58) ) Fields surveyed (Int. Cl. ⁷ , DB name) A61K ⁷ /00-7/50 A61K 31/185-31/27 A61K 31/44-31/455 CA (STN)

Claims (1)

(57) [Claims] 1. An external preparation for skin comprising at least one cyclohexanecarboxylic acid derivative represented by the following general formula 1. Embedded image [Wherein A is phenyl, pyridyl, p-isopropenylphenyl, or a compound represented by the general formula 2] (Where X ₁ represents a hydrogen atom, a hydroxyl group or a methoxy group, X ₂ represents a hydrogen atom, a hydroxyl group or a methoxy group,
₃ is a hydroxyl group, a methoxy group, a halogen atom, a nitro group, a trifluoromethyl group, a carboxyl group or a general formula 3
Are shown below). , R represents a hydrogen atom, Na or an alkyl group having 1 to 4 carbon atoms, and R ₁ represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, respectively]