JP3519191B2 - External preparation for skin - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a skin external preparation having excellent effects of preventing skin aging, such as moisturizing the skin, preventing and improving rough skin, and preventing and improving wrinkle formation.

[0002]

2. Description of the Related Art In recent years, maintaining healthy and beautiful skin has become a serious concern for men and women of all ages. However, the skin is subtly affected by aging, temperature, humidity, ultraviolet rays, cosmetics, diseases, stress, eating habits, etc., and therefore various functions of the skin (prevention of loss of water etc. from the living body and constant body temperature). Various functions, such as the function to control the physical maintenance, the physical and chemical stimuli from the outside world and the function to protect the body from various bacteria, the function to maintain the elasticity of the skin and determine the surface morphology), the aging of the skin, etc. Trouble occurs.

Further, as described above, the skin trouble is caused by a change in the external environment (seasonal change, ultraviolet rays, etc.) and a function of the skin tissue due to internal and external factors acting on the living body such as changes in physiological functions due to aging and diseases. In addition to abnormalities, it is caused by skin thickening and parakeratosis induced by these.

A major attempt to prevent or ameliorate such skin troubles is to apply a synthetic or natural moisturizing component to prevent the skin from drying and increase the moisturizing ability of the skin.
Methods for improving the promotion of blood circulation by applying a blood circulation accelerator have been made.

That is, free amino acids, organic acids, urea,
Inorganic ions, moisturizers such as polysaccharides such as hyaluronic acid, animal and plant extracts, vitamins and their derivatives, peptides, proteins, and the like, by using a medicated external preparation for skin and cosmetics containing the hydroxy acid Attempts have been made to prevent and improve the disease.

However, even if such a component is applied to the skin, its effect is low and it is temporary, and it has not been essential to prevent or ameliorate the skin trouble.

On the other hand, wrinkles, which are one of the skin troubles, occur due to aging due to aging, drying, ultraviolet rays and the like.
That is, dryness, changes in the surface morphology of the epidermis due to physical and chemical stimuli from the outside such as ultraviolet rays and aging, diseases, degeneration of tissues in the dermis due to stress, etc., in particular, collagen fibers are largely lost and degeneration of the dermis, The skin ages due to a decrease in subcutaneous adipose tissue, etc., which mainly causes wrinkle relaxation and loss of elasticity.

Conventionally, various compositions and methods have been proposed in order to suppress or treat such wrinkles due to aging (Japanese Patent Laid-Open No. 185005/1987).
JP-A-62-502546, JP-A-2-7215
No. 7, JP-A-2-288822, etc.). However, none of these showed a satisfactory wrinkle reducing effect.

[0009]

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a skin external preparation having excellent anti-aging effects such as moisturizing effect, prevention / improvement of rough skin, and prevention / improvement of wrinkle formation. It is in.

[0010]

Under such circumstances, as a result of intensive studies, the present inventors have found that, when a plant extract and a specific amide derivative are used in combination, a skin external preparation excellent in the effect of preventing skin aging. The inventors have found that the following can be obtained and completed the present invention.

That is, the present invention provides the following components (A) and (B): (A) Hamamelis, button, Agrimony japonica, cowpea,
0.0001 to 20% by weight in terms of dry solid content of one or more plant extracts selected from asunaro, holtsou, Hikioshi, and Pheasant, (B) the following general formula (1)

[0012]

[Chemical 5]

(In the formula, R ¹ and R ² are the same or different and each represents a linear or branched, saturated or unsaturated, optionally hydroxylated hydrocarbon group having 1 to 40 carbon atoms, and R ³
Represents a linear or branched alkylene group having 1 to 6 carbon atoms or a single bond, R ⁴ represents a hydrogen atom, a linear or branched alkoxy group having 1 to 12 carbon atoms, or a 2,3-dihydroxypropyloxy group. Indicates. However, when R ³ is a single bond, R ⁴ is a hydrogen atom. )

[0014]

[0015]

[0016]

[0017]

[0018]

1 selected from amide derivatives represented by
The present invention provides a skin external preparation containing one or more kinds.

[0020]

BEST MODE FOR CARRYING OUT THE INVENTION The plant extract of the component (A) used in the present invention is obtained from plants of hamamelis, peony, buttercup, caterpillar, asunaro, holtsaw, cypress, and pheasant.

[0021]

The extract is dried or without drying at least one or more parts (hereinafter referred to as the "material") of the whole plant of each plant or its leaves, bark, roots, branches, fruits, flowers and the like. After crushing, it can be obtained by extraction with a solvent at room temperature or under heating, or extraction using an extraction device such as a Soxhlet extractor. Here, the solvent used is not particularly limited, and examples thereof include water, primary alcohols such as methyl alcohol and ethyl alcohol, propylene glycol,
Liquid polyhydric alcohol such as 1,3-butylene glycol,
Known solvents include lower alkyl esters such as ethyl acetate, hydrocarbons such as benzene and hexane, and known solvents such as ethyl ether and acetone. These solvents may be used alone or in combination.
Combinations of more than one species can be used. As a specific example of a preferable extraction method from the drug substance, a dry pulverized product 100
1000 ml of 50 v / v% ethanol is added to the gram, and extraction is performed for 3 days at room temperature with occasional stirring. The extract thus obtained is filtered, the filtrate is allowed to stand at 5 ° C. for 3 days and then filtered again to obtain a supernatant. The plant extract obtained under the above conditions may be used as it is as an extracted solution, but if necessary, it may be subjected to treatments such as concentration, filtration and drying.

The plant extract of the component (A) can be used alone or in combination of two or more kinds, and the blending amount thereof is 0.0001 to 20% by weight in the whole composition in terms of dry solid content.
(Hereinafter, simply expressed as%)
It is preferable to add 10% to 10%, more preferably 0.0001% to 5% in order to obtain a sufficient effect of preventing and improving wrinkle formation.

The amide derivative of the component (B) used in the present invention is represented by the above general formula (1).

In the amide derivative (1) used in the present invention, R ¹ and R ² are the same or different and are linear or branched, saturated or unsaturated, optionally hydroxylated hydrocarbons having 1 to 40 carbon atoms. Indicates a group. R ¹ and R ² are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, heneicosyl, docosyl, Nonacosyl, triacontyl, isostearyl, isoheptadecyl, 2
-Ethylhexyl, 1-ethylheptyl, 8-heptadecyl, 8-heptadecenyl, 8,11-heptadecadienyl, 2-heptylundecyl, 9-octadecenyl,
1-hydroxynonyl, 1-hydroxypentadecyl,
2-hydroxypentadecyl, 15-hydroxypentadecyl, 11-hydroxyheptadecyl, 11-hydroxy-8-heptadecenyl and the like can be mentioned.

R ¹ is preferably a linear or branched alkyl or alkenyl group having 8 to 26 carbon atoms, for example, octyl, decyl, dodecyl, tetradecyl, hexadecyl, octadecyl, docosyl, triacontyl, isostearyl, 2-ethylhexyl, 2-heptyl undecyl, 9-octadecenyl and the like can be mentioned. A particularly preferable hydrocarbon group as R ¹ is a linear or branched alkyl group having 12 to 22 carbon atoms, and examples thereof include dodecyl, tetradecyl, hexadecyl, octadecyl, docosyl and methyl-branched isostearyl groups.

R ² is preferably a linear or branched alkyl or alkenyl group having 9 to 25 carbon atoms, for example, nonyl, undecyl, tridecyl, pentadecyl, heptadecyl, heneicosyl, nonacosyl, isoheptadecyl, 1-ethylheptyl, 8- Heptadecyl, 8-heptadecenyl, 8,11-heptadecadienyl, 1-hydroxynonyl, 1-hydroxypentadecyl, 2-hydroxypentadecyl, 15-hydroxypentadecyl,
11-hydroxyheptadecyl and 11-hydroxy-
8-heptadecenyl and the like can be mentioned. Particularly preferred hydrocarbon groups as R ² are linear and branched alkyl groups having 11 to 21 carbon atoms, such as undecyl, tridecyl,
Pentadecyl, heptadecyl, heneicosyl, methyl-branched isoheptadecyl group and the like can be mentioned.

R³Is a straight or branched chain having 1 to 6 carbon atoms
Represents an alkylene group or a single bond, and as an alkylene group
Is, for example, methylene, ethylene, trimethylene, tetrame
Tylene, pentamethylene, hexamethylene, 1-methyl
Ethylene, 1-methyltrimethylene, 2-methyltrimethyl
Ethylene, 1,1-dimethylethylene, 1-ethylethylene
1-methyltetramethylene, 2-ethyltrimethylene
And the like. R ³As a straight chain having 1 to 6 carbon atoms
Alkylene groups are preferred, of which methylene and ethylene
And trimethylene are particularly preferred.

R ⁴ represents a hydrogen atom, a linear or branched alkoxy group having 1 to 12 carbon atoms or a 2,3-dihydroxypropyloxy group, and examples of the alkoxy group include methoxy, ethoxy, propoxy, butoxy and hexyloxy. , Octyloxy, decyloxy, 1-methylethoxy, 2-ethylhexyloxy and the like.
R ⁴ is preferably a hydrogen atom, an alkoxy group having 1 to 8 carbon atoms or a 2,3-dihydroxypropyloxy group,
Of these, hydrogen atom, methoxy, ethoxy, propoxy,
Butoxy, 1-methylethoxy, 2-ethylhexyloxy and 2,3-dihydroxypropyloxy groups are particularly preferred.

Among the amide derivatives (1), a particularly preferred compound is a compound in which R ¹ , R ² , R ³ and R ⁴ in the general formula are each a group in the above particularly preferred range. .

[0031]

[0032]

[0033]

The amide derivative (1) of the component (B) can be obtained, for example, by the following production method 1 or production method 2.

[0035]

[Chemical 9]

[0036]

[Chemical 10]

(In the formula, R ¹ , R ² and R ³ have the same meanings as described above, and R ^4f represents a hydrogen atom or a linear or branched alkoxy group having 1 to 12 carbon atoms. ³
When is a single bond, R ^4f is a hydrogen atom. R ⁶ , R ⁸ ,
R ¹⁰ and R ¹¹ represent a linear or branched saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms, preferably 1 to 8 carbon atoms.
5 is a linear or branched alkyl group, particularly preferably a methyl group. R ⁹ is a hydrogen atom, an alkali metal atom or
COR ⁸ group is shown, and R ⁷ and R ¹² are leaving groups such as halogen atom, mesylate group and tosylate group. For R ⁷ ,
A chlorine atom and a bromine atom, especially a chlorine atom is preferable from the viewpoint of easy availability, and R ¹² is preferably a mesylate group and a tosylate group from the viewpoint of easy availability. )

[0038]

[Chemical 11]

[0039]

[Chemical 12]

(In the formula, R ¹ , R ² , and R ^{6 to} R ¹² have the same meanings as described above, and R ^3g represents a linear or branched alkylene group having 1 to 6 carbon atoms.)

The reaction conditions in each step of production method 1 and production method 2 are as follows.

Step 1) Glycidyl ether (7) and amine (8F) or (8G), without solvent, or with water or a lower alcohol such as methanol, ethanol or isopropanol, or an ether system such as tetrahydrofuran, dioxane or ethylene glycol dimethyl ether. Amino alcohol derivative (2F) or (2G) is produced by reacting at room temperature to 150 ° C. in a solvent, a hydrocarbon solvent such as hexane, benzene, toluene, xylene, or an arbitrary mixed solvent thereof. You can

Step 2) Amino alcohol derivative (2F)
Alternatively, (2G), a fatty acid ester (9), preferably a fatty acid lower alkyl ester such as fatty acid methyl ester or fatty acid ethyl ester, an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, an alkaline earth such as calcium hydroxide. Of basic catalysts such as alkali metal carbonates such as group metal hydroxides, potassium carbonate and other alkali metal carbonates, calcium carbonate and other alkaline earth metal carbonates, sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like. The amide derivative (3F) or (3G) can be produced by reacting in the presence of a normal pressure to a reduced pressure of 0.01 mmHg at room temperature to 150 ° C. At this time, the amount of the basic catalyst used is preferably 0.01 to 0.2 equivalents relative to the amino alcohol derivative (2F) or (2G), and when the alcohol generated by the reaction is removed outside the system, the reaction Is preferable because it progresses rapidly.

Step 3) Amide derivative (3F) or (3
G) is also an amino alcohol derivative (2F) or (2
G) is fatty acid chloride (10) without solvent or a halogenated hydrocarbon solvent such as chloroform, methylene chloride, 1,2-dichloroethane, tetrahydrofuran,
In the presence of a base such as pyridine or a tertiary amine such as triethylamine in an ether solvent such as dioxane or ethylene glycol dimethyl ether, a hydrocarbon solvent such as hexane, benzene, toluene, or xylene, or an arbitrary mixed solvent thereof. Or, in the absence, room temperature to 10
After reacting at 0 ° C. to convert to an amide-ester derivative (11F) or (11G),

Step 4) The ester group is converted to an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, an alkali metal carbonate such as potassium carbonate or calcium carbonate. Alkaline earth metal carbonates such as, sodium methoxide, sodium ethoxide, potassium-tert-butoxide and the like, under alkaline conditions such as alkali metal alcoholates, etc., can also be produced by selective hydrolysis. .

Step 5) Amide derivative (3F) or (3
1 to 20 equivalents of epoxide (12), preferably epichlorohydrin, in G) without solvent or with water or an ether solvent such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, hexane, benzene,
1 to 10 equivalents of an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide or an alkaline earth metal water such as calcium hydroxide in a hydrocarbon solvent such as toluene or xylene, or an arbitrary mixed solvent thereof. Oxide,
Room temperature to 150 ° C in the presence of an alkali metal carbonate such as potassium carbonate or an alkaline earth metal carbonate such as calcium carbonate
The amide derivative (4F) or (4
G) can be produced. At this time, tetrabutylammonium bromide, tetrabutylammonium chloride, hexadecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide,
Stearyl trimethyl ammonium chloride, bis-tetraoxyethylene stearyl methyl ammonium chloride and the like quaternary ammonium salts and lauryl dimethylcarboxyammonium betaine It is preferable to perform the reaction in the presence of a phase transfer catalyst such as betaine in terms of yield and the like. .

Step 6) Amide derivative (4F) or (4
G) is an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, an alkali metal carbonate such as potassium carbonate, an alkaline earth metal carbonate such as calcium carbonate Basic conditions such as salts or mineral acids such as sulfuric acid and hydrochloric acid, Lewis acids such as boron trifluoride and tin tetrachloride, carboxylic acids such as acetic acid, tetradecanoic acid and hexadecanoic acid, and sulfonic acids such as p-toluenesulfonic acid. The amide derivative (1F) or (1G) can be produced by hydrating at room temperature to 300 ° C. under acidic conditions such as the above or under mixed conditions of base and acid.

Step 7) Amide derivative (1F) or (1
G) also includes a carboxylic acid derivative (13), preferably a lower fatty acid such as acetic acid, an alkali metal salt of a lower fatty acid such as sodium acetate, or a lower fatty acid anhydride such as acetic anhydride, in addition to the amide derivative (4F) or (4G). Alternatively, in combination, after reacting in the presence or absence of a basic catalyst such as a tertiary amine such as triethylamine to convert the ester-amide derivative (14F) or (14G),

Step 8) The ester group is converted to an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, an alkali metal carbonate such as potassium carbonate or calcium carbonate. Alkaline earth metal carbonates such as, sodium methoxide, sodium ethoxide, potassium-tert-butoxide and the like, under alkaline conditions such as alkali metal alcoholates, etc., can also be produced by selective hydrolysis. .

Step 9) Amide derivative (1F) or (1
G) is also a carbonyl derivative (4F) or (4G) with a carbonyl compound (15), preferably a lower aliphatic ketone such as acetone or methyl ethyl ketone, a mineral acid such as sulfuric acid, hydrochloric acid or phosphoric acid, or a carboxylic acid such as acetic acid. After conversion into a 1,3-dioxolane-amide derivative (16F) or (16G) by reacting in the presence of an acid catalyst such as Lewis acid such as boron trifluoride or tin tetrachloride,

Step 10) Mineral acids such as sulfuric acid, hydrochloric acid and phosphoric acid,
It can also be produced by deketalization under acidic conditions such as carboxylic acid such as acetic acid and sulfonic acid such as p-toluenesulfonic acid.

Step 11) The 1,3-dioxolane-amide derivative (16F) or (16G) is also converted into the amide derivative (3F) or (3G) by the glycerol derivative (17).
An alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, an alkali metal carbonate such as potassium carbonate, an alkaline earth metal carbonate such as calcium carbonate, In the presence of a base such as an alkali metal hydride such as sodium hydride, or without a solvent, or an aprotic polar solvent such as N, N-dimethylformamide or dimethylsulfoxide, an ether solvent such as tetrahydrofuran, dioxane, or ethylene glycol dimethyl ether. It can also be produced by reacting in a hydrocarbon solvent such as hexane, benzene, toluene, xylene, or a mixed solvent thereof.

The amide derivative (1) of the component (B) of the present invention thus obtained can be purified by a known method. When the amide derivative (1) is blended in a skin external preparation and a hair cosmetic composition, even a purified product purified to 100% has a purity of 70 to 100% containing an intermediate or a reaction by-product without any particular purification. Even if it is a mixture, it is excellent in effect and performance and has no problem in safety. The compounds of the present invention also include solvates represented by hydrates.

Examples of the amide derivative (1) of the component (B) obtained by the production method 1 include the following.

[0055]

[Chemical 13]

[0056]

[Chemical 14]

Examples of the amide derivative (1) of the component (B) of the present invention obtained by the production method 2 include the following.

[0058]

[Chemical 15]

In the external preparation for skin of the present invention, the component (B)
The amide derivative can be used singly or in combination of two or more, and the blending amount thereof is not particularly limited, but is preferably 0.01 to 50% in the total composition, It is preferable to add 0.01 to 20%, more preferably 0.1 to 10% from the viewpoint of feeling in use and prevention of skin aging.

The external preparation for skin of the present invention contains the above essential components, and further contains one or more selected from the following components (C), (D), (E) and (F). The effect of the invention can be further enhanced.

As a component (C), when an acidic heteropolysaccharide derived from a callus of a plant belonging to the genus Polyanthes is blended,
It is preferable because the protective effect on the skin is reinforced and a higher effect of preventing skin aging such as prevention and improvement of wrinkle formation is obtained. Ingredient (C), Polyanthes
L. Callus-derived acidic heteropolysaccharides (hereinafter referred to as “acidic polysaccharides”) of plants belonging to
According to the method described in Japanese Patent Publication No. 10997, callus derived from a plant belonging to the genus Polyantes can be cultured and collected from the obtained culture. As a plant belonging to the genus Polyantes, there is a tuberose (Poliant).
hes tuberosa L. ) Is mentioned as a preferable example, and it is preferable to use modified heteropolysaccharide derived from callus of tuberose as the component (C).

As a method for collecting the acidic polysaccharide, for example, in the case of tuberose, the following tissue culture method can be used. That is, a part of a tuberose flower or the like was used as an explant in Linsmaier-skoo's basal medium, and 10 ⁻⁵ M auxin and 1 were added as plant hormones.
Add 0 ^-6 M cytokinin and add 3 as a carbon source.
After inducing callus using a medium to which saccharose is added, subculture is performed, and then shake culture is performed using a liquid medium containing the same components as the above callus culture medium. After that, cells are removed from the culture solution by centrifugation or filtration, the culture solution is concentrated using a rotary evaporator, etc., the concentrated solution is added with a solvent such as ethanol or acetone to cause precipitation, and the precipitate is freeze-dried. Thus, the acidic polysaccharide can be separated and obtained.

The acidic polysaccharide thus obtained is preferably added in an amount of 0.0001 to 20% in the total composition,
It is particularly preferable to add 0.001 to 10%, more preferably 0.01 to 10%, because a more sufficient effect of preventing skin aging can be obtained.

When sterols are blended as the component (D), penetration of the components (A) and (B) into the skin is enhanced,
This is preferable because a higher effect of preventing and improving wrinkle formation can be obtained. Examples of such sterols include cholesterol or a cholesterol derivative, and examples of the cholesterol derivative include cholesteryl alkenylsuccinate, cholestanol, a saturated or unsaturated straight chain or branched chain having 12 to 36 carbon atoms, preferably 14 to 28 carbon atoms. Examples thereof include cholesteryl ester having a chain hydrocarbon group, dehydrocholesterol and the like. Among these, cholesteryl alkenyl succinate is synthesized by the production method described in JP-A-5-294989, for example, n-hexadecenyl succinic acid cholesteryl monoester, n-octadecenyl succinic acid cholesteryl ester. Examples thereof include monoesters.
Examples of the cholesteryl ester include cholesteryl isostearate, cholesteryl 1,2-hydroxystearate, lanolin fatty acid cholesteryl, and cholesteryl ricinoleate. Of these, cholesteryl alkenyl succinate, cholesterol and cholesteryl isostearate are preferred.

The sterols of the component (D) may be one kind or two kinds.
Although more than one species may be used in combination, the amount is not particularly limited, but is preferably 0.01 to 50% in the total composition, particularly 0.01 to 40.0%, and more preferably 0.01.
It is preferably about 20%.

Further, it is preferable to add an anti-inflammatory substance as the component (E) because the effect of suppressing inflammation caused by ultraviolet rays and the like is enhanced and a higher effect of preventing and improving wrinkle formation is obtained. Examples of such anti-inflammatory substances include glycyrrhizic acid and salts thereof, glycyrrhetinic acid and salts thereof, epsilon aminocaproic acid and salts thereof, allantoin, lysozyme chloride, guaiazulene, methyl salicylate, γ
-Oryzanol and the like can be mentioned, and of these, glycyrrhetinic acid, stearyl glycyrrhetinate, and epsilon aminocaproic acid are preferable.

The anti-inflammatory substance of component (E) may be used alone or in combination of two or more, and may be used in an amount of 0.00
It is preferable to add 1 to 5%, particularly 0.01 to 2%,
Further, it is preferable to add 0.01 to 1%.

Furthermore, when a singlet oxygen scavenger or an antioxidant is added as the component (F), the effect of detoxifying the peroxide and active oxygen is enhanced, and a higher effect of preventing and improving wrinkle formation is obtained. preferable. Examples of the singlet oxygen scavenger or antioxidant include, for example, α-carotene, β-carotene, γ-carotene, lycopene, clybutoxanthin, lutein, zeaxanthin, isoseaxanthin, rhodoxanthin,
Carotenoids such as capsanthin and crocetin; 1,4-
Diazacyclooctane, 2,5-dimethylfuran, 2-
Methylfuran, 2,5-diphenylfuran, 1,3-diphenylisobenzofuran, α-tocopherol, β-tocopherol, γ-tocopherol, d-tocopherol, histidine, tryptophan, methionine, alanine or an alkyl ester thereof; dibutylhydroxytoluene,
Tannins such as butylhydroxyanisole, ascorbic acid, tannic acid, epicatechin, epicarocatechin, epicatechin gallate, epicarocatechin gallate,
Examples thereof include flavonoids such as rutin. Of these, carotene, tocopherol, ascorbic acid, tannic acid, epicatechin gallate, and epicarocatechin gallate are preferable.

The singlet oxygen scavenger or antioxidant of the component (F) can be used alone or in combination of two or more,
It is preferably 0.001 to 5%, more preferably 0.01 to 2%, further preferably 0.01 to 1% in the total composition.

The external preparation for skin of the present invention is roughly classified into a medicated external preparation for skin and cosmetics depending on its form. Examples of the external medicated skin preparation include various ointments containing medicinal components. Here, the ointment may be one based on an oily base, one based on oil / water, or one based on an emulsion base of water / oil type. The oily base is not particularly limited, and examples thereof include vegetable oils, animal oils, synthetic oils, fatty acids and natural or synthetic glycerides, ceramides, pseudoceramides and the like. Furthermore, the medicinal component is not particularly limited, and includes, for example, analgesic and anti-inflammatory agents, antipruritic agents,
A bactericidal / disinfectant, an astringent, an emollient, a hormonal agent and the like can be appropriately used if necessary.

As the cosmetics, various forms such as water / oil or oil / water emulsion cosmetics, creams, lotions, lotions, oily cosmetics, packs, lipsticks, foundations, skin cleansing agents, It can be used as a skin cosmetic such as a hairnic, a hair styling agent, a hair nourishing agent, and a hair restorer. In the case of cosmetics, in addition to the above-mentioned essential components, components that are blended in ordinary cosmetics within the range that does not impair the effects of the present invention, such as oils, water, surfactants, pH regulators, ceramides, Pseudo-ceramides, moisturizers, alcohols, chelating agents, ultraviolet absorbers, preservatives, thickeners, dyes, fragrances and the like can be added as necessary.

Examples of the oil agent include hydrocarbons such as solid or liquid paraffin, petrolatum, crystal oil, ceresin, ozokerite, montan wax, squalane, squalene, olive oil, carnauba wax, lanolin, jojoba oil, glycerin monostearate, Glycerin distearate, glycerin monooleate, isopropyl stearate, ester oil such as neopentyl glycol dicaprate, higher fatty acids such as stearic acid and palmitic acid, and higher alcohols such as cetanol and stearyl alcohol can be used. . When these oil agents are blended, it is preferably blended in the cosmetic in an amount of 0.01 to 50%, particularly preferably 0.1 to 30%.

Water can be used as a base together with ethanol and a water-soluble polyhydric alcohol. As the water-soluble polyhydric alcohol, one containing two or more hydroxyl groups in the molecule, for example, ethylene glycol, propylene glycol, 1,3-butylene glycol, 1,4-
Butylene glycol, dipropylene glycol, glycerin and polyglycerin such as diglycerin, triglycerin, tetraglycerin, glucose, maltose, maltitol, sucrose, fructose, xylitol, sorbitol, maltotriose, threitol, erythritol, starch-reducing sugar reduction Examples thereof include alcohols, and one or more of these can be used.
When these water, ethanol, and water-soluble polyhydric alcohol are blended, the blending amount in the cosmetic can be appropriately set according to the dosage form, but usually the sum of these is 0.0
It is preferable to add 1 to 95%, particularly 1
It is preferable to mix it up to 90%.

When the product of the present invention is emulsified or solubilized, it is preferable to add a surfactant. Examples of the surfactant include polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbitol fatty acid ester, glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil alkyl sulfate, polyoxyethylene. Examples thereof include ethylene alkyl sulfate ester, alkyl phosphate ester, polyoxyethylene alkyl phosphate ester, fatty acid alkali metal salt, sorbitan fatty acid ester, glycerin fatty acid ester, and alkyl glyceryl ether. These may be used alone or in combination. it can. When these surfactants are blended, it is preferably blended in the cosmetic in an amount of 0.01 to 50%, particularly preferably 0.1 to 30%.

The external preparation for skin of the present invention may further contain silicones as an oil or a surfactant.
The silicones are not particularly limited as long as they are usually blended in cosmetics, and include, for example, octamethylpolysiloxane, tetradecamethylpolysiloxane, methylpolysiloxane, highly polymerized methylpolysiloxane, methylphenylpolysiloxane. In addition to siloxane, octamethylcyclotetrasiloxane, methyl polycyclosiloxane such as decamethylcyclopentasiloxane, trimethylsiloxysilicic acid, and further modified polyether modified silicone, polyether alkyl modified silicone, alkyl glyceryl ether modified silicone, etc. Silicone etc. can be mentioned. When blending these silicones, the blending amount in the cosmetic is such as dimethylpolysiloxane, when used as an oil component, when using as a surfactant such as polyether modified silicone, when a non-silicone oil component or It may be adjusted so that the total amount with the surfactant is the above-mentioned amount.

The external preparation for skin of the present invention may be further blended with a powder to obtain a make-up cosmetic such as a foundation. Examples of the powder include mica, talc, sericite, kaolin, nylon powder, extender pigments such as polymethylsilsesquioxane, inorganic pigments such as pearl, red 202, red 226, yellow 4, and organic such as aluminum lake. Examples thereof include pigments, zinc oxide, titanium oxide, zirconium oxide, iron oxide, and other inorganic powders for protecting ultraviolet rays. These powders are treated with silicone such as methylhydrogenmethylpolysiloxane, trimethylsiloxysilicic acid and methylpolysiloxane, fluorine treatment with perfluoroalkyl phosphate ester, perfluoroalcohol and the like, amino acid treatment with N-acylglutamic acid and the like, Those treated with lecithin, metal soap, fatty acid, alkyl phosphate, etc. can also be used. When these powders are blended, the blending amount in the cosmetic can be appropriately set depending on the dosage form, but it is usually preferable to blend 0.1 to 50%, and especially 1 to 30%. Is preferred.

The external preparation for skin of the present invention may further contain a pH adjusting agent to improve the stability of color and odor of the ingredients such as plant extract. The pH adjuster is not particularly limited, but sodium hydroxide, potassium hydroxide,
Metal hydroxides such as lithium hydroxide, triethanolamine, isopropanolamine, diisopropanolamine, urea, ε-aminocaproic acid, sodium pyrrolidonecarboxylate, sodium hydrogenphosphate, sodium citrate, citric acid, lactic acid, succinic acid, Examples thereof include organic acids such as tartaric acid and betaines such as glycine betaine and lysine betaine. The pH of the external preparation for skin of the present invention is 4 to 10
It is desirable to set the area.

In addition to the above-mentioned components, the external preparation for skin of the present invention may contain various components which are usually contained in cosmetics, quasi-drugs, pharmaceuticals, etc. within a range not impairing the object of the present invention. it can. Examples of such components include magnesium sulfate, potassium sulfate, sodium sulfate,
Inorganic salts such as magnesium chloride and sodium chloride; polyvinyl alcohol, carboxyvinyl polymer, carboxymethyl cellulose, gelatin, tragacanth gum, xanthan gum, hyaluronic acid, agarose, sodium alginate and the like viscosity modifiers; parabens and other preservatives, UV absorbers, pigments , Medicinal components, fragrances and the like.

[0079]

EFFECTS OF THE INVENTION The external preparation for skin of the present invention is used synergistically for moisturizing skin, preventing / ameliorating rough skin, preventing / improving wrinkle formation, etc. by using a combination of a plant extract and a specific amide derivative. A high effect of preventing skin aging is obtained.

[0080]

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

The plant extract of component (A) was produced by the following method so that the dry solid content was 0.1 to 20%.
In the examples, the plant extracts obtained in these Production Examples 1 to 8 were used.

Production Example 1 Method for Producing Hamamelis Extract 50 per 100 g of dry pulverized hamamelis leaves and bark
Add 1,000 ml of v / v% ethanol and perform extraction for 3 days at room temperature with occasional stirring. The obtained extract is filtered,
The filtrate was allowed to stand at 5 ° C. for 3 days and then filtered again to obtain a supernatant.

Production Example 2 Production Method of Button Extract Instead of the dried and ground product of Hamamelis in Production Example 1,
It was produced in the same manner as in Production Example 1, except that a dried and crushed root bark was used.

Production Example 3 Production Method of Agrimony japonicus Extract In place of the dried pulverized product of Hamamelis in Production Example 1,
It was produced in the same manner as in Production Example 1 except that a dried and crushed whole product of Agrimony arvense was used.

Production Example 4 Production Method of Catalpa Extract Instead of the dried and ground product of Hamamelis in Production Example 1,
It was produced in the same manner as in Production Example 1 except that dry milled fruits of Cattle Bean were used.

Production Example 5 Production Method of Asunaro Extract Production Example 1 except that the dry pulverized product of asunaro leaf bark was used in place of the dried pulverized product of Hamamelis in Production Example 1.
It was manufactured in the same manner as.

Production Example 6 Production Method of Spinach Extract Except for that in Production Example 1, dried pulverized product of Holmose seed or whole grass was used in place of dried pulverized product of Hamamelis.
It was produced in the same manner as in Production Example 1.

Production Example 7 Production Method of Hiki-Okoshi Extract Production Example 1 except that the dried and ground product of Hamamelis was used in place of the dried and ground product of Hamamelis in Production Example 1.
It was manufactured in the same manner as.

Production Example 8 Production Method of Pheasant Extract Extract Production was carried out in the same manner as in Production Example 1, except that the dried and crushed product of Hamamelis was used instead of the dried and crushed product of Hamamelis.

Example 1 O / W creams having the following compositions were produced, and the effect of suppressing wrinkle formation when these creams were used was evaluated by the following method. Structure of amide derivative used and plant extract (Production Examples 1 to 1
No. 8) and other ingredients and their amounts (% by weight) are shown in Table 1.
4 to 4 (1 to 14 are present products, 15 to 18 are comparative products), the composition of the O / W cream is shown in Table 5, and the evaluation result of the wrinkle formation suppressing effect is shown in Table 6.

[0091]

[Table 1]

[0092]

[Table 2]

[0093]

[Table 3]

[0094]

[Table 4]

[0095]

(Table 5) (Composition) (%) (1) Amide derivative (Tables 1 to 4) Tables 1 to 4 (2) Plant extract, etc. (Tables 1 to 4) Tables 1 to 4 (3) Glycerin 1.0 ( 4) Polyoxyethylene (10) hydrogenated castor oil 1.0 (5) sorbitan monostearate 0.5 (6) stearoyl methyl taurine sodium 0.5 (7) polyoxyethylene lauryl ether sodium phosphate 0.5 (8) ) Cetostearyl alcohol 2.0 (9) Squalane 2.0 (10) Neopentyl glycol dicaprate 8.0 (11) Methyl polysiloxane ^{* 1} 4.0 (12) Cyclic silicone ^{* 2} 4.0 (13) Preservative Agent Appropriate amount (14) Purified water Remaining amount (15) Ethanol 3.0 (16) Perfume Appropriate amount meter 100.0 * 1: Silicone KF96A (6cs), Shin-Etsu Chemical Co., Ltd. * 2: Silicone SH-244, SH-245 Or SH-244 and SH-245 3: 2 (weight ratio Mixture, manufactured by Dow Corning Toray Silicone Co., Ltd.

(Production method) Oil phase component [(1), (4),
(5), (7) to (11)] are heated and dissolved at 80 ° C, and the aqueous phase components [(3), (6), (12), (13), which are heated to 80 ° C with stirring, (14)] was added and emulsified, and the mixture was stirred and cooled to 50 ° C., then the components [(2), (12), (15) and (16)] were added, and the mixture was further stirred and cooled to room temperature. / W cream was prepared.

(Evaluation method) An emulsified cosmetic (80 μl) was applied to hairless mice, and after 2 hours, UV-B (1M
(ED and below), and immediately after that, another sample was applied. This operation was performed 5 times a week for 16 weeks. The amount of irradiation energy is UV-Radiometer (Tokyo)
optical, UV-R-305 / 365 days), and a total irradiation dose of 100 mJ at an energy dose of 0.28 mW / cm ² so that the single dose of irradiation is 1 MED or less.
/ Cm ² . After completion of application / irradiation for 16 weeks, the frequency of the wrinkles formed was visually evaluated by the following criteria (wrinkle index).

Standard (wrinkle index): 1: No wrinkles formed. 2: Slightly formed wrinkles. 3: Some wrinkles formed. 4: Strongly formed wrinkles.

[0099]

[Table 6]

Example 2 (O / W Moisturizing Emulsion) An O / W moisturizing emulsion having the composition shown below was produced by a conventional method. The obtained emulsion had an excellent effect of suppressing wrinkle formation.

[0101]

[Table 7] (Composition) (%) Amide derivative (the same as the product 1 of the present invention in Tables 1 to 4) 3.0 Hamamelis extract (dry solid content 1.5%) 0.5 Button extract (dry) Solid content 1.0%) 0.5 Cetyl alcohol 1.0 Vaseline 2.0 Squalane 5.0 Dimethylpolysiloxane (6 cSt) 2.0 Glycerin 4.0 1,3-Butylene glycol 2.0 Polyoxyethylene ( 20) Sorbitan monooleate 0.5 Sorbitan monostearate 0.3 Acidic polysaccharide (the same as in Example 1) 1.0 n-hexadecenyl succinic acid cholesteryl monoester 1.0 stearyl glycyrrhetinate 1.0 Tocopherol 1.0 Succinic acid 0.55 Sodium dihydrogen phosphate 0.9 Purified water Fuel gauge 100.0

Example 3 (Sunscreen Emulsion) A sunscreen emulsion having the following composition was produced by a conventional method. The obtained emulsion had an excellent effect of suppressing wrinkle formation.

[0103]

[Table 8] (Composition) (%) Amide derivative (the same as the product 1 of the present invention in Tables 1 to 4) 2.0 Hamamelis extract (dry solid content 1.5%) 0.5 Hikikoshi extract (dry) Solid content 1.5%) 0.5 Octyl paramethoxycinnamate 6.0 4-tert-butyl-4-methoxybenzoylmethane 2.0 oleyloleate 5.0 Dimethylpolysiloxane (6cSt) 3.0 Vaseline 0 .5 Cetyl alcohol 1.0 Sorbitan sesquioleate ester 0.8 Polyoxyethylene (20) oleyl alcohol ether 1.2 Dipropylene glycol 6.0 Acidic polysaccharide (the same as in Example 1) 1.0 Ethanol 3. 0 hydroxyethyl cellulose 0.3 n-octadecenyl succinic acid cholesteryl monoester 1.0 glycyrrhetinic acid stearyl 1.0 Coferol 1.0 Succinic acid 0.2 Sodium hydroxide 0.2 Purified water Fuel gauge 100.0

Example 4 (Sunscreen Cream) A sunscreen cream having the composition shown below was produced by a conventional method. The obtained cream was excellent in the effect of preventing skin aging.

[0105]

[Table 9] (Composition) (%) Amide derivative (same as the product 1 of the present invention in Tables 1 to 4) 3.0 Silicone-coated zinc oxide 7.0 p-Methoxycinnamic acid 2-ethylhexyl 2.0 Ascorbic acid 0 .5 Cholesterol 1.0 Polyether-modified silicone ^{* 1} 2.5 Methylpolysiloxane ^{* 2} 6.0 Cyclic silicone ^{* 3} 12.0 Magnesium sulfate 0.7 Acidic polysaccharide (the same as in Example 1) Allantoin 0.1 Quercus chinensis extract (dry solid content 1.0%) 0.5 Hortosou extract (dry solid content 1.0%) 0.5 Glycerin 3.0 Preservative A suitable amount of purified water Residual amount 100.0

* 1: Silicone KF-6015, manufactured by Shin-Etsu Chemical Co., Ltd. * 2: Silicone KF-96A (6cs), manufactured by Shin-Etsu Chemical Co., Ltd. * 3: Silicone SH-244, SH-245 or SH-244 and SH- 245 3: 2 (weight ratio) mixture, manufactured by Toray Dow Corning Silicone

Continuation of the front page (56) References JP-A 64-31752 (JP, A) JP-A 64-9913 (JP, A) JP-A 6-157276 (JP, A) JP-A 60-258104 (JP , A) JP 63-57510 (JP, A) JP 3-157334 (JP, A) JP 4-235117 (JP, A) JP 5-139950 (JP, A) JP 7-133216 (JP, A) JP 58-23612 (JP, A) JP 7-196526 (JP, A) JP 5-97648 (JP, A) JP 7-165528 (JP, A) JP-A-5-345719 (JP, A) JP-A-63-150208 (JP, A) JP-A-7-17847 (JP, A) JP-A-5-105613 (JP, A) JP-A-62 -67027 (JP, A) JP-A-6-206814 (JP, A) JP-A-6-80576 (JP, A) JP-A 1-213213 (JP, A) JP-A-5-339141 (JP, A) (58) Fields surveyed (Int.Cl. ⁷ , DB name) A61K 7/00 -7/50 CA (STN) REGISTRY ( STN)

Claims (10)

(57) [Claims] 1. The following components (A) and (B): (A) Hamamelis, button, Agrimony japonica, cowpea,
0.0001 to 20% by weight of one or more kinds of plant extracts selected from asunaro, holtsow, Hiki-Oshi, and Pheasant, calculated as dry solids, (B) the following general formula (1) 1] (In the formula, R ¹ and R ² are the same or different and have 1 to 4 carbon atoms.
0 represents a straight chain or branched chain saturated or unsaturated hydrocarbon group which may be hydroxylated, and R ³ has 1 to 1 carbon atoms.
6 represents a linear or branched alkylene group or a single bond, and R ⁴ represents a hydrogen atom, a linear or branched alkoxy group having 1 to 12 carbon atoms, or a 2,3-dihydroxypropyloxy group. However, when R ³ is a single bond, R ⁴ is a hydrogen atom. An external skin preparation containing one or more selected from the amide derivatives represented by 2. The method according to claim 1, further comprising (C) an acidic heteropolysaccharide derived from a callus of a plant belonging to the genus Polyanthes.
The skin external preparation described. 3. The external preparation for skin according to claim 1, further comprising (D) a sterol. 4. The external preparation for skin according to any one of claims 1 to 3, further comprising (E) an anti-inflammatory substance. 5. The method according to claim 1, further comprising (F) one or more selected from singlet oxygen scavengers and antioxidants.
The external preparation for skin according to any one of 1 to 4. 6. The amide derivative of component (B) is 0.01 to
The external preparation for skin according to any one of claims 1 to 5, which contains 50% by weight. 7. The component (C) is an acidic heteropolysaccharide derived from callus of tuberose, and the content thereof is 0.0.
The external preparation for skin according to any one of claims 2 to 6, which is 001 to 20% by weight. 8. The sterols of component (D) is one or more selected from cholesteryl alkenyl succinate, cholesterol and cholesteryl isostearate, and the content thereof is 0.01 to 50% by weight. Item 9. The external preparation for skin according to any one of items 3 to 7. 9. The anti-inflammatory substance as component (E) is one or more selected from glycyrrhetinic acid, stearyl glycyrrhetinate and epsilon aminocaproic acid, and the content thereof is 0.001 to 5% by weight. Claim 4 ~
The external preparation for skin according to any one of 8 above. 10. The singlet oxygen scavenger or antioxidant of component (F) is carotene, tocopherol, ascorbic acid,
It is 1 type (s) or 2 or more types selected from tannic acid, epicatechin gallate, and epicarocatechin gallate, and the content is 0.001-5 weight%.
The external preparation for skin according to any one of 1.