JPH09165313A - Skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin preparation for external use having preventing effects on skin aging such as humectation of the skin by synergistic effects of a plant extract with a specific amide derivative. SOLUTION: This skin preparation for external use comprises one or more plant extracts such as Hamamelis virgianiana L. or Paeonia suffruticosa Andr. and one or more compounds selected from among amide derivatives represented by formula I (R<1> and R<2> are each independently a 1-40C hydrocarbon, etc.; R<3> is a 1-6C alkylene, etc., or a single bond; R<4> is H, a 1-12C alkoxy, etc., with the proviso that R<4> is H when R<3> is a single bond), formula II (R<1a> is a 4-40C hydrocarbon; R<3a> is a 3-6C alkylene, etc.; R<4a> is a 1-12C alkoxy, etc.), and formula III or IV (R<4b> is H, a 1-12C alkoxy, etc., with the proviso that R<4b> is H when R<3> is a single bond).

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 is excellent in skin aging prevention effects 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.

[0004] The main attempts to prevent and improve such skin troubles are to apply a synthetic or natural moisturizing component to prevent the skin from drying and to enhance the moisturizing ability of the skin.
Methods for improving the promotion of blood circulation by applying a blood circulation promoting agent have been made.

That is, free amino acids, organic acids, urea,
The use of humectants such as inorganic ions and polysaccharides such as hyaluronic acid, animal and plant extracts, vitamins and derivatives thereof, peptides, proteins, and medicated skin external preparations and cosmetics containing hydroxy acids, etc., causes the above skin troubles. Attempts have been made to prevent and improve

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 Accordingly, an object of the present invention is to provide a skin external preparation which is excellent in skin aging prevention effects such as moisturizing effects, prevention and improvement effects of rough skin, and prevention and improvement effects 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) one or more kinds of plant extracts, (B) the following general formulas (1), (2), ( 3) and (4)

[0012]

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(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]

[Chemical 6]

(In the formula, R ^1a represents an optionally hydroxylated hydrocarbon group having 4 to 40 carbon atoms, R ^3a represents a linear or branched alkylene group having 3 to 6 carbon atoms, and R ^{3 4a}
Represents a linear or branched alkoxy group having 1 to 12 carbon atoms. )

[0016]

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(In the formula, R ¹ and R ² are the same or different and each represents an optionally hydroxylated hydrocarbon group having 1 to 40 carbon atoms, and R ^3a is a straight chain or branched chain having 3 to 6 carbon atoms. R ^4a represents a linear or branched alkoxy group having 1 to 12 carbon atoms.)

[0018]

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(In the formula, R ¹ and R ² are the same or different and each represents an optionally hydroxylated hydrocarbon group having 1 to 40 carbon atoms, and R ³ is a linear or branched chain having 1 to 6 carbon atoms. Represents an alkylene group or a single bond, R ^4b is a hydrogen atom,
It represents a linear or branched alkoxy group having 1 to 12 carbon atoms or a 2,3-epoxypropyloxy group. However,
When R ³ is a single bond, R ^4b is a hydrogen atom. The present invention provides a skin external preparation containing one or more selected from amide derivatives represented by the formula (1).

[0020]

BEST MODE FOR CARRYING OUT THE INVENTION The plant extract of component (A) used in the present invention includes ashitaba, azuki bean, avocado, amateur, armchair, arteca, arnica, almond, aloe, apricot, nettle, iris, fennel,
Turmeric, Ages, Ougon, Ooaku, Oren, Barley, Okra, Hypericum perforatum, Odorikosou, Ononis, Dutch mustard, oyster, cuckoo, chamomile, birch, cattail, chamomile, chamomile, oak, oat, licorice, strawberry, kiwi, kiwi, cucumber, cucumber, cucumber , Gardenia, kumazasa, walnuts, keihi, mulberry, gunjou, gentian, genosho,
Burdock, sesame, wheat, rice, sasanqua, saffron, hawthorn, hawthorn, shiitake, dio, shikon, perilla,
Linden, spirea, peony, ginger,
Ginger, birch, honeysuckle, horsetail, stevia,
Prickly pear, Hawk's hawthorn, Sambucus nigra, Prickly pear, Achillea millefolium, Peppermint, sage, mallow, ginkgo, senburi, soybean, daisou, thyme, tea, clove, chimp, evening primrose, camellia, lacquer tree, euphorbifolia, spruce, quince sp. Tonnin, spruce, corn, hemlock, tomato, carrot, garlic, novara, stag beetle, parsley, hadakamugi, pearl barley, peppermint, pahaiya, hamamelis, rose, hinoki, sunflower, loquat, butterbur, dandelion, grape, placenta, hazelnut, loofah, Safflower, bodaiju, buttons, hops, macadamia nuts, pine, horse chestnut, melissa, merlot, peach, moyashi, cornflower, palm, eucalyptus, yukinoshita, lily, yokuinin, yo Formic, rye, peanut, lavender, apple, litchi, lettuce, lemon, Rengesou, rosemary, Roman chamomile, agrimony, catalpa, dolabrata, Horutosou, cause, date,
Senki, chickweed, floating grass, wormwood, ginkgo,
Examples thereof include those obtained from plants such as kyoto, chrysanthemum, kumazasa, swordfish, and forsythia.

In the present invention, of these, extracts of hamamelis, button, quince cypress, cowpea, asunaro, holtso, hikikoshi and pheasant are particularly preferable.

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.
More than one species can be used in combination. 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 obtained extract is filtered, and 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) may be used alone or in combination of two or more kinds, and the compounding amount thereof is not particularly limited, but it is 0 in the whole composition in terms of dry solid content. .0
001 to 20% by weight (hereinafter, simply referred to as%) is preferably blended, particularly 0.0001 to 10%, and further 0.00
It is preferable to add 01 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 formulas (1) to (4).

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. As R ¹ and R ² , 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.

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. Particularly preferred hydrocarbon groups for R ¹ are linear or branched alkyl groups having 12 to 22 carbon atoms, such as 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 and methyl-branched isoheptadecyl groups.

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

In the amide derivative (2) used in the present invention, R ^1a represents an optionally hydroxylated hydrocarbon group having 4 to 40 carbon atoms, and specifically, R ¹ to methyl in the amide derivative (1). , And groups excluding ethyl and propyl are mentioned, and a group similar to R ¹ is preferable. R ^3a represents a linear or branched alkylene group having 3 to 6 carbon atoms, and specific examples thereof include a group obtained by removing methylene and ethylene from the alkylene group exemplified in R ³ of the amide derivative (1). R ^3a is preferably a straight-chain alkylene group having 3 to 6 carbon atoms, and among them, trimethylene is particularly preferable. R
Examples of the linear or branched alkoxy group having 1 to 12 carbon atoms represented by ^4a include the same groups as R ⁴ of the amide derivative (1), and the same groups are preferable.

The amide derivative (3) used in the present invention
In, R¹, R^Two, R^3aAnd R ^4aIs the same as above
Tastes similar and similar groups are preferred.

The amide derivative (4) used in the present invention
In the above, R ¹ , R ² and R ³ have the same meanings as described above, and R ^4b represents a hydrogen atom, a linear or branched alkoxy group having 1 to 12 carbon atoms or a 2,3-epoxypropyloxy group. . Specific examples of R ¹ , R ² and R ³ include the same groups as in the amide derivative (1), and the same groups are preferable. Examples of the linear or branched alkoxy group having 1 to 12 carbon atoms for R ^4b include the same groups as R ⁴ of the amide derivative (1), and include a hydrogen atom, an alkoxy group similar to R ⁴ , and 2,3. -An epoxypropyloxy group is preferred.

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

[0035]

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[0036]

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(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
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]

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[0039]

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(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)
Or (2G) a fatty acid ester (9), preferably a fatty acid lower alkyl ester such as a fatty acid methyl ester or a fatty acid ethyl ester, or an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, or an alkaline earth such as calcium hydroxide. Alkaline catalysts such as alkali metal carbonates such as metal hydroxides and potassium carbonate, alkaline earth metal carbonates such as calcium carbonate, alkali metal alcoholates such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; The amide derivative (3F) or (3G) can be produced by reacting at room temperature to 150 ° C. under reduced pressure of normal pressure to 0.01 mmHg in the presence. At this time, the amount of the basic catalyst used is preferably 0.01 to 0.2 equivalent relative to the amino alcohol derivative (2F) or (2G). Is preferred because it proceeds quickly.

Step 3) Amide derivative (3F) or (3
G) is also an amino alcohol derivative (2F) or (2
G) 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 a tertiary amine such as pyridine or triethylamine in an ethereal solvent such as dioxane or ethylene glycol dimethyl ether, a hydrocarbon-based solvent such as hexane, benzene, toluene or xylene, or an arbitrary mixed solvent thereof. Or in the absence of, room temperature to 10
After reaction at 0 ° C. to convert to 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
G) 1 to 20 equivalents of epoxide (12), preferably epichlorohydrin, without solvent or water or an ether solvent such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, hexane, benzene,
In a hydrocarbon solvent such as toluene or xylene, or an arbitrary mixture thereof, 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. Oxides,
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 manufactured. At this time, tetrabutylammonium bromide, tetrabutylammonium chloride, hexadecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide,
Stearyltrimethylammonium chloride, bistetraoxyethylene stearylmethylammonium chloride or other quaternary ammonium salts or lauryldimethylcarboxyammonium betaine or other phase transfer catalyst such as betaine is preferable to perform the reaction in terms of yield and the like. .

Step 6) Amide derivative (4F) or (4
G) represents 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 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 hydration at room temperature to 300 ° C. under acidic conditions such as those described above or under a base-acid mixed condition.

Step 7) Amide derivative (1F) or (1
G) is 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, alone with the amide derivative (4F) or (4G). Alternatively, in combination, the mixture is reacted in the presence or absence of a basic catalyst such as a tertiary amine such as triethylamine to convert it into an 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) can also be obtained by adding a carbonyl compound (15), preferably a lower aliphatic ketone such as acetone or methyl ethyl ketone, to a amide derivative (4F) or (4G), a mineral acid such as sulfuric acid, hydrochloric acid or phosphoric acid, or a carboxylic acid such as acetic acid. , Boron trifluoride, tin tetrachloride or the like, and reacted in the presence of an acid catalyst such as a Lewis acid to convert to a 1,3-dioxolane-amide derivative (16F) or (16G).

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).
A potassium hydroxide, an alkali metal hydroxide such as 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, in the absence of a solvent or an aprotic polar solvent such as N, N-dimethylformamide or dimethyl sulfoxide, or an ether solvent such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether or the like. And hexane, benzene, toluene, xylene and the like, or a mixed solvent thereof, or the like.

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]

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[0056]

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

[0058]

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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
And oryzanol; and among 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 preferred.

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 medicated skin external preparation include various ointments containing a pharmaceutically active ingredient. Here, the ointment may be any of those based on an oily base and those based on an oil / water or water / oil emulsion type base. The oleaginous base is not particularly limited, and examples thereof include vegetable oils, animal oils, synthetic oils, fatty acids, and natural or synthetic glycerides, ceramides, and pseudoceramides. Further, the medicinal component is not particularly limited, for example, an analgesic anti-inflammatory, an antipruritic,
A disinfectant, an astringent, an emollient, a hormonal agent, and the like can be appropriately used as needed.

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 acid such as stearic acid and palmitic acid, higher alcohol such as cetanol and stearyl alcohol, etc. 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 dried 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 In place of the dry 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 described above.

Production Example 6 Production Method of Spinach Extract Except that in Example 1 the dried ground product of Hamamelis was used in place of the dried ground product of Holtflower seeds or whole grass.
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 a dry-ground product of Hiki-Okoshi whole grass was used in place of the dried ground product of Hamamelis in Production Example 1.
It was manufactured in the same manner as described above.

Production Example 8 Production Method of Pheasant Extract Extract was produced in the same manner as in Production Example 1, except that the dried and crushed product of Hamamelis was used in place 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 Suitable amount (14) Purified water Remaining amount (15) Ethanol 3.0 (16) Perfume Suitable amount 100.0 * 1: Silicone KF96A (6cs), manufactured by Shin-Etsu Chemical Co., Ltd. * 2: Silicone SH-244, SH-245 Or SH-244 and SH-245 3: 2 (weight ratio ) Mixture, manufactured by Toray Dow Corning Silicone

(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 five 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 the application / irradiation for 16 weeks was completed, the frequency of the formed wrinkles was visually evaluated according to the following criteria (wrinkle index).

Standard (wrinkle index): 1: No wrinkles formed. 2: Wrinkles are slightly formed. 3: Some wrinkles are formed. 4: Wrinkles are firmly formed.

[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

Claims (11)

[Claims] 1. The following components (A) and (B): (A) one or more plant extracts, (B) the following general formulas (1), (2), (3) and ( 4) [Chemical 1] (Wherein R ¹ and R ² are the same or different and each 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. ) (In the formula, R ^1a represents an optionally hydroxylated hydrocarbon group having 4 to 40 carbon atoms, R ^3a represents a linear or branched alkylene group having 3 to 6 carbon atoms, and R ^4a represents a carbon atom. Number 1
12 straight-chain or branched-chain alkoxy groups are shown. ) (Wherein R ¹ and R ² are the same or different and each have 1 to 4 carbon atoms)
0 represents an optionally hydroxylated hydrocarbon group; R ^3a represents a straight-chain or branched-chain alkylene group having 3 to 6 carbon atoms; R ^4a represents a straight-chain or branched-chain alkyl group having 1 to 12 carbon atoms; Shows an alkoxy group. ) [Chemical 4] (Wherein R ¹ and R ² are the same or different and each have 1 to 4 carbon atoms)
0 represents an optionally hydroxylated hydrocarbon group; R ³ represents a linear or branched alkylene group having 1 to 6 carbon atoms or a single bond; R ^4b represents a hydrogen atom;
12 linear or branched alkoxy groups or 2,3-
Shows an epoxypropyloxy group. However, when R ³ is a single bond, R ^4b 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 topical skin preparation according to the above. 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 plant extract of component (A) is Hamamelis,
It is one or two or more kinds of plant extracts selected from button, Agrimony japonicus, Catalpa, Asunaro, Holtose, Hizokushi, and Pheasant, and its content is 0.0001 to 20% by weight in terms of dry solid content. Claim 1
The external preparation for skin according to any one of 5 above. 7. The amide derivative of component (B) is 0.01 to
The external preparation for skin according to any one of claims 1 to 6, which contains 50% by weight. 8. 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 7, which is 001 to 20% by weight. 9. The sterol of component (D) is one or more selected from cholesteryl alkenylsuccinate, cholesterol and cholesteryl isostearate, and the content thereof is 0.01 to 50% by weight. Item 9. The external skin preparation according to any one of items 3 to 8. 10. The anti-inflammatory substance of 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.
The external preparation for skin according to any one of 1 to 9. 11. 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 0.