JP2003171269A - Skin care preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation resistant to the separation and precipitation of ceramides without using a surfactant, a phospholipid, etc., having excellent storage stability and easily giving a transparent to turbid appearance by the adjustment of the components. <P>SOLUTION: The skin care preparation is an emulsion free from acrylic acid polymer or phospholipid and containing (A) a sphingosine expressed by general formula (1) (R<SP>1</SP>is a (substituted) hydrocarbon group; R<SP>2</SP>and R<SP>3</SP>are each OH or the like; Y is methylene, methine, oxygen or the like; X<SP>1</SP>, X<SP>2</SP>and X<SP>3</SP>are each H, OH or the like; X<SP>4</SP>is H or the like; R is H or amidino; and (a) is 2 or 3), (B) an inorganic acid or a ≤5C organic acid and (C) a ceramide expressed by general formula (2) (R<SP>7</SP>is a (substituted) alkyl; Z is methylene, methine, oxygen or the like; R<SP>8</SP>and R<SP>9</SP>are each H, OH or the like; X<SP>4</SP>, X<SP>5</SP>, X<SP>6</SP>and X<SP>7</SP>are each H, OH or the like; R<SP>10</SP>and R<SP>11</SP>are each a substituent) at an ((A)+(B))/(C) weight ratio of ≥0.0001. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a skin external preparation containing ceramides, which is excellent in storage stability, rough skin improving effect and skin barrier property and is highly safe.

[0002]

BACKGROUND OF THE INVENTION The stratum corneum, which is the outermost layer of the skin, suppresses the invasion of substances from the outside and the evaporation of water from the inside of the skin, and at the same time, it retains the water itself to make the skin soft and smooth. It has the function of maintaining the appearance. A lipid called inter-corneocyte lipid (hereinafter, referred to as horny layer ICL) is present in the space between horny cells forming the horny layer so as to fill the keratinocyte gap.

About 50% of the lipid composition of the stratum corneum ICL is ceramide, which is composed of other substances such as cholesterol, cholesterol ester and fatty acid. Generally, it is known that a decrease in stratum corneum ICL, particularly ceramide, causes undesired skin conditions such as rough skin, dry skin, and aged skin. By supplementing ceramide as an ingredient for improving stratum corneum function by external use, the function is improved. It can improve the deteriorated stratum corneum condition (J. Invest. Dermatol., 84: 282 (1985), J. Invest.
Dermatol., 87: 758 (1986)).

[0004] However, ceramide has a problem that it is difficult to stabilize it in a formulation because it has strong crystallinity and a high melting point. Therefore, in order to stably mix with the external preparation for skin,
It is inevitable to use together with a surfactant, various kinds, a large amount of oil agents, etc. As a result, it is inevitable that the feeling of use is deteriorated and the properties of the preparation are limited.

On the other hand, sphingosine is also a lipid present in the stratum corneum ICL (J. Invest. Dermatol., 94: 159.
(1990)). Sphingosine is a long-chain amino alcohol mainly contained in gangliosides in the living body, and analogues such as dihydrosphingosine and phytosphingosine exist and is known as a substance having anti-acne and anti-inflammatory physiological activity. This long chain amino alcohol is
Generally, it is generically called sphingoid, and ceramide is a compound in which sphingoid and a fatty acid are amide-bonded. But,
The function of sphingosine in the stratum corneum has not been elucidated.

Japanese Unexamined Patent Publication No. 2001-48721 discloses a phospholipid, a ceramide, which is a main component of stratum corneum ICL, cholesterol, a fatty acid having 6 to 25 carbon atoms, and a physiologically active substance, phytosphingosine or a derivative thereof. Surfactant-based skin protection cream compositions are disclosed. However, in order to obtain a stable creamy composition, ceramide, in a system that does not use a synthetic surfactant,
Multiple lipids and phospholipids must be used in combination. Phospholipids are the main components of the cell membranes of the dermis and the deep side of the epidermis (Malpighian cells), but gradually decrease toward the stratum corneum, and almost do not exist in the stratum corneum ICL, and ceramide is the main component (J Lipid Res., 24: 131 (1983)).
Therefore, in the stratum corneum ICL, phospholipids are essentially unnecessary components and have surface-active properties. In JP-A-2001-48721, a phospholipid is used instead of the synthetic surfactant, and the stability of the preparation containing ceramide and the reduction in the feeling of use are insufficient.

Therefore, there has been a demand for an external preparation for skin which has a simple composition and is capable of stably blending ceramide and exerting a sufficient effect.

[0008]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a skin external preparation for stable emulsification of ceramides such as ceramide or a derivative thereof and having a high effect of improving rough skin.

[0009]

Means for Solving the Problems The present inventors have found that when ceramides are emulsified with sphingosines and an acid, the ceramides can be stably retained without crystallization, and in particular, natural or synthetic surfactants and phosphorus. Without adding lipids,
Ceramide can be stably retained with a simple composition, and by changing the ratio of the amount of sphingosines and the total amount of acid to the amount of ceramides, the transparency (transparent to cloudy color) and properties of appearance color can be changed. It was found that the external preparation for skin having different uses can be obtained.

The present invention provides the following components (A), (B) and (C): (A) sphingosines represented by the general formula (1),

[0011]

[Chemical 3]

(In the formula, R ¹ has 4 to 3 carbon atoms, which may be substituted with a hydroxyl group, a carbonyl group or an amino group.
0 represents a straight chain, branched chain or cyclic saturated or unsaturated hydrocarbon group; Y represents either a methylene group, a methine group or an oxygen atom; X ¹ , X ² and X ³ are each independently Represents a hydrogen atom, a hydroxyl group, or an acetoxy group, and X ⁴
Represents a hydrogen atom, an acetyl group or a glyceryl group, or forms an oxo group together with an adjacent oxygen atom (provided that when Y is a methine group, either X ¹ or X ² is a hydrogen atom). And the other does not exist. When X ⁴ forms an oxo group, X ³ does not exist.); R ² and R ³ each independently represent a hydrogen atom, a hydroxyl group, a hydroxymethyl group or an acetoxymethyl group. A's R's each independently represent a hydrogen atom or an amidino group, or have a total carbon number of 1 to 8 which may have a substituent selected from a hydroxyl group, a hydroxyalkoxy group, an alkoxy group and an acetoxy group.
Represents a straight chain or branched chain saturated or unsaturated hydrocarbon group; a represents a number of 2 or 3; and a broken line part represents that an unsaturated bond may be present. ) (B) Inorganic acid or organic acid having 5 or less carbon atoms, (C) Ceramide represented by the general formula (2)

[0013]

[Chemical 4]

(In the formula, R⁷Is a hydroxyl group
4 to 3 carbon atoms, which may be substituted by a phenyl group or an amino group.
0 straight chain, branched chain or cyclic saturated or unsaturated hydrocarbons
Represents a group; Z is a methylene group, a methine group, or an oxygen atom
Indicates the deviation; X^Five, X⁶And X ⁷Each independently hydrogen source
Represents a child, a hydroxyl group, or an acetoxy group, and X^FourIs
Indicates a hydrogen atom, acetyl group or glyceryl group, or is adjacent
Form an oxo group together with the oxygen atom
When Z is a methine group, X^FiveAnd X⁶One of is a hydrogen atom
And the other does not exist. X^FourForms an oxo group
Time X⁷Does not exist. ); R⁸And R⁹Each independently
Hydrogen atom, hydroxyl group, hydroxymethyl group, or
Represents an acetoxymethyl group; R^TenIs a hydroxyl group,
In the main chain, which may be substituted with a rubonyl group or amino group
Has an ether bond, ester bond, or amide bond
May be straight-chain, branched-chain or cyclic saturated with 5 to 60 carbon atoms
Or an unsaturated hydrocarbon group; R¹¹Represents a hydrogen atom
Or hydroxyl group, hydroxyalkoxy group, alcohol
Having a substituent selected from xy and acetoxy groups
May be saturated or straight chain or branched chain having 1 to 8 total carbon atoms or
Unsaturated hydrocarbon group is shown; the broken line is an unsaturated bond.
Indicates that it is okay. ) Containing an emulsion,
Content weight ratio ((A) + (B)) / (C) is 0.00
01 or more, an acrylic acid polymer or phospholipid
It is intended to provide a skin external preparation that does not contain.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION R ¹ of the sphingosines represented by the general formula (1) (component (A)) used in the present invention is
A hydroxyl group, a carbonyl group or an amino group may be substituted, and a C4 to C30, preferably a C7 to C22 optionally substituted by a hydroxyl group is a linear, branched or cyclic saturated or unsaturated group. It is a saturated hydrocarbon group. In particular,
A straight-chain or branched-chain alkyl group having 10 to 20 carbon atoms, a straight-chain or branched-chain alkyl group having 10 to 20 carbon atoms having a hydroxyl group at the Y-side end, and in the case of a branched-chain alkyl group, the branched chain is methyl. Branched ones and the like are preferable. Specifically, a tridecyl group, a tetradecyl group, a pentadecyl group, a hexadecyl group, a 1-hydroxytridecyl group, a 1-hydroxypentadecyl group, an isohexadecyl group, and an isostearyl group are preferable.

Y is a methylene group (CH ₂ ) or a methine group (C
H) or oxygen atom. X ¹ , X ² , and X
Each ³ independently represents a hydrogen atom, a hydroxyl group, or an acetoxy group, and X ⁴ represents a hydrogen atom, an acetyl group, a glyceryl group, or a substituent which forms an oxo group together with an adjacent oxygen atom. Particularly preferred is one in which 0 to ¹ of X ¹ , X ² and X ³ are hydroxyl groups, the remainder is a hydrogen atom, and X ⁴ is a hydrogen atom. When Y is a methine group, only ^one of X ¹ and X ² is a hydrogen atom and the other does not exist. Further, when X ⁴ forms an oxo group, X ³ does not exist.

R ² and R ³ each independently represent a hydrogen atom, a hydroxyl group, a hydroxymethyl group or an acetoxymethyl group, and R ³ is particularly preferably a hydrogen atom.

Further, a represents a number of 2 or 3, when a is 2, R represents R ⁴ and R ^5, and when a is 3, R represents R ⁴ , R ⁵ and R ⁶ .

R ⁴ , R ⁵ and R ⁶ are each independently a hydrogen atom or an amidino group, or may have a substituent selected from a hydroxyl group, a hydroxyalkoxy group, an alkoxy group and an acetoxy group. A linear or branched saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms is shown. As the hydroxyalkoxy group which can be substituted with the hydrocarbon group, a linear or branched hydroxyalkoxy group having 1 to 7 carbon atoms is preferable. Also, the alkoxy group has 1 carbon atom.
A linear or branched alkoxy group of ˜7 is preferred.
R ⁴ , R ⁵ and R ⁶ are, for example, hydrogen atom; methyl,
Linear or branched alkyl groups such as ethyl, propyl, 2-ethylhexyl and isopropyl; alkenyl groups such as vinyl and allyl; amidino groups; hydroxymethyl, 2-hydroxyethyl, 1,1-dimethyl-2-hydroxyethyl , 2-hydroxypropyl, 2,3-dihydroxypropyl, 2-hydroxy-3-methoxypropyl, 2,
3,4,5,6-pentahydroxyhexyl, 1,1-
Bis (hydroxymethyl) ethyl, 2- (2-hydroxyethoxy) ethyl, 2-methoxyethyl, 1-methyl-2-hydroxyethyl, 3-hydroxypropyl, 3
Examples thereof include a hydrocarbon group having 1 to 8 total carbon atoms, which is substituted with 1 to 6 selected from hydroxy, hydroxyalkyl and alkoxy such as -methoxypropyl and 1,1-bis (hydroxymethyl) -2-hydroxyethyl. Especially hydrogen atom, or methyl group, 2-hydroxyethyl, 1,1
1 to 3 selected from a hydroxy group and a hydroxyalkoxy group such as dimethyl-2-hydroxyethyl, 1,1-bis (hydroxymethyl) ethyl or 2- (2-hydroxyethoxy) ethyl may be substituted. Alkyl groups are preferred.

The sphingosines represented by the general formula (1) used in the present invention are preferably natural or natural sphingosines represented by the following general formula (3):
And derivatives thereof (hereinafter referred to as natural sphingosine).

[0021]

[Chemical 5]

(In the formula, R ¹² represents a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 7 to 19 carbon atoms which may be substituted with a hydroxyl group; Y ₁ represents a methylene group or Represents a methine group; X ⁸ , X ⁹ and X ¹⁰ each independently represent a hydrogen atom, a hydroxyl group or an acetoxy group, and X ¹¹
Represents a hydrogen atom or forms an oxo group together with an adjacent oxygen atom (provided that when Y ₁ is a methine group, X ⁸ and X
^{One of 9} represents a hydrogen atom and the other is absent. X ¹⁰ is absent when X ¹¹ forms an oxo group. ); R ¹³ represents a hydroxymethyl group or an acetoxymethyl group; a R _{1 s} each independently represent a hydrogen atom or an amidino group, or a substituent selected from a hydroxy group, a hydroxyalkoxy group, an alkoxy group and an acetoxy group. Represents a linear or branched saturated or unsaturated hydrocarbon group having 1 to 4 carbon atoms which may have a group; a represents a number of 2 or 3; Indicates that it is good. )

R ¹² is preferably a linear, branched or cyclic, saturated or unsaturated hydrocarbon group having 7 to 19 carbon atoms, and particularly preferably a linear saturated or unsaturated hydrocarbon group having 13 to 15 carbon atoms. Hydrocarbon groups are preferred. a is preferably 2 and each R ₁ is independently a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms.

Specific examples of the natural sphingosine represented by the general formula (3) include natural sphingosine,
Examples thereof include dihydrosphingosine, phytosphingosine, sphingadienin, dehydrosphingosine, dehydrophytosphingosine, and N-alkyl compounds (for example, N-methyl compounds) thereof. These sphingosines may be used in the form of natural (D (+) form) or non-natural (L (−) form).
Further, a mixture of natural type and non-natural type may be used. The relative configuration of the above compound may be a natural configuration,
Other non-natural type configurations may be used,
It may be a mixture of these. Especially PHYTOSPHINGO
Those represented by SINE (INCI name; 8th Edition) and the following formulas are preferable.

[0025]

[Chemical 6]

These may be natural extracts or synthetic products, and commercially available products can be used. As commercially available natural sphingosines, for example,
D-Sphingosine (4-Sphingenine) (SIGMA-ALDRICH), DS-
Examples include phytosphingosine (DOOSAN) and phytosphingosine (Cosmo Farm).

Further, as another type of sphingosines represented by the general formula (1) in the present invention, a pseudo type having a sphingosine structure represented by the following general formula (4) (hereinafter referred to as pseudo type sphingosine is described. ).

[0028]

[Chemical 7]

(In the formula, R ¹⁷ represents a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 10 to 22 carbon atoms which may be substituted with a hydroxyl group; X ⁴ represents a hydrogen atom;
An acetyl group or a glyceryl group; each a ₂ R ₂ independently represents a hydrogen atom or an amidino group, or may have a substituent selected from a hydroxyl group, a hydroxyalkoxy group, an alkoxy group and an acetoxy group. A good straight or branched chain saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms is shown, and a is a number of 2 or 3. )

Here, as R ¹⁷ , an iso-branched alkyl group having 14 to 20 carbon atoms is preferable, and an isostearyl group is particularly preferable. The isostearyl group is most preferably an isostearyl group obtained by using, as a raw material oil, an isostearal alcohol derived from a by-product at the time of producing a dimer acid using a fatty acid derived from an animal or vegetable oil. When a is 2, R ₂ represents R ¹⁸ and R ^19, and when a is 3, R ₂ is R ¹⁸ , R ¹⁹ and R ²⁰ . R ¹⁸ , R ¹⁹ and R ²⁰ are, for example, a hydrogen atom; a linear or branched alkyl group such as methyl, ethyl, propyl, 2-ethylhexyl and isopropyl; an alkenyl group such as vinyl and allyl; an amidino group; hydroxy Methyl, 2
-Hydroxyethyl, 1,1-dimethyl-2-hydroxyethyl, 2-hydroxypropyl, 2,3-dihydroxypropyl, 2-hydroxy-3-methoxypropyl, 2,3,4,5,6-pentahydroxyhexyl ,
1,1-bis (hydroxymethyl) ethyl, 2- (2-
Hydroxyethoxy) ethyl, 2-methoxyethyl, 1
-Total carbon having a substituent selected from hydroxy, hydroxyalkoxy and alkoxy such as methyl-2-hydroxyethyl, 3-hydroxypropyl, 3-methoxypropyl and 1,1-bis (hydroxymethyl) -2-hydroxyethyl. The alkyl groups of the numbers 1 to 8 are mentioned. In particular, one of R ¹⁸ and R ¹⁹ is a hydrogen atom, and the other is 2-hydroxyethyl, 1,1-dimethyl-2-hydroxyethyl, 1,1-bis (hydroxymethyl) ethyl, 2- (2- A secondary amine which is hydroxyethoxy) ethyl is preferred.

Pseudo-type sphingosines include R ¹⁷ as an isostearyl group, X ^{4 as} a hydrogen atom, R ¹⁸ as a hydrogen atom, R ¹⁹ as a 2-hydroxyethyl group, and a 1,1-bis (hydroxymethyl) ethyl group. , 1,1-dimethyl-2-hydroxyethyl group, or 2- (2-hydroxyethoxy) ethyl group and the like are preferably alkyl groups having 1 to 3 substituents selected from hydroxy groups and hydroxyalkoxy groups.

Specific examples of the pseudo-type sphingosines include those of the following formula.

[0033]

[Chemical 8]

Two or more kinds of component (A) may be used in combination.
The content of the component (A) in the external preparation for skin of the present invention is 0.0
It is preferably from 10 to 10% by weight, more preferably from 0.005 to 3% by weight, and particularly preferably from 0.01 to 1.5% by weight.

Examples of the inorganic acid or the organic acid having a carbon number of 5 or less (component (B)) used in the present invention include phosphoric acid, hydrochloric acid, nitric acid, sulfuric acid, perchloric acid, carbonic acid, and the like. Phosphoric acid and hydrochloric acid are preferred.

Examples of the organic acid include monocarboxylic acids such as formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid and valeric acid; dicarboxylic acids such as succinic acid, phthalic acid, fumaric acid, oxalic acid, malonic acid and glutaric acid; Examples thereof include oxycarboxylic acids such as glycolic acid, citric acid, lactic acid, pyruvic acid, malic acid and tartaric acid; amino acids such as glutamic acid and aspartic acid.

As specific examples of the component (B), phosphoric acid, hydrochloric acid, succinic acid, citric acid, lactic acid, glutamic acid, aspartic acid and the like are preferable, and lactic acid, glutamic acid and aspartic acid are particularly preferable.

The component (B) may be used in combination of two or more kinds. The content of the component (B) in the external preparation for skin of the present invention is
0.001-10% by weight, more preferably 0.005-
It is preferably 3% by weight, especially 0.001 to 1.5% by weight.

The component (B) is used in order to cationize the amine of the component (A), the amount of the component (A) is 0.3 mol or more, preferably 0.3 to 5 mol, and more preferably 0, relative to 1 mol of the component (A). It is preferably contained in an amount of 0.5 to 3 mol. For example, the pH of an aqueous solution that is equimolar with the component (A) is 2 to 6 at 25 ° C.
Is preferred (for example, after correction with phthalate standard solution, measured with HORIBA pH METER F-22).

R ⁷ of the component (C) ceramide represented by the general formula (2) of the present invention has 4 to 3 carbon atoms, which may be substituted with a hydroxyl group, a carbonyl group or an amino group.
0 is a linear, branched or cyclic, saturated or unsaturated hydrocarbon group having 7 to 22 carbon atoms, which may be substituted with a hydroxyl group. Z represents either a methylene group, a methine group or an oxygen atom. X ⁵ , X ⁶ and X ⁷ each independently represent a hydrogen atom, a hydroxy group or an acetoxy group. In particular, it is preferable that 0 to 1 of X ⁵ , X ⁶ and X ⁷ are hydroxyl groups, and the balance is a hydrogen atom. X ⁶ is absent when Z is a methine group. Also, X ⁴
Is preferably a hydrogen atom or a glyceryl group. R ⁸
And R ⁹ represents a hydrogen atom, a hydroxyl group, a hydroxymethyl group, or an acetoxymethyl group, and preferred R ⁸
Is a hydrogen atom or a hydroxymethyl group, and preferred R is
⁹ is a hydrogen atom. R ¹⁰ may be substituted with a hydroxyl group, a carboxy group or an amino group, and may have an ether bond, an ester bond or an amide bond in the main chain, and may have a straight chain, branched chain or C 5-60 carbon atom. It represents a cyclic saturated or unsaturated hydrocarbon group. Preferably, a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 5 to 35 carbon atoms which may be substituted with a hydroxyl group or an amino group,
Alternatively, at the ω-position of the hydrocarbon group, a straight-chain, branched or cyclic saturated or unsaturated fatty acid having 8 to 22 carbon atoms which may be substituted by a hydroxyl group is ester-bonded or amide-bonded. As the fatty acid to be bound, isostearic acid, 12-hydroxystearic acid or linoleic acid is preferable. R ¹¹ represents a hydrogen atom, a hydroxy group,
A total carbon number of 1 to 1 which may have a substituent selected from a hydroxyalkoxy group, an alkoxy group and an acetoxy group.
8 is a straight or branched chain saturated or unsaturated hydrocarbon group. Of these, hydrogen atom, or 1 to 3 selected from a hydroxy group, a hydroxyalkoxy group, and an alkoxy group.
A hydrocarbon group having 1 to 8 total carbon atoms, which may be substituted, is preferable. Here, the hydroxyalkoxy group and the alkoxy group preferably have 1 to 7 carbon atoms.

The ceramides represented by the general formula (2) of the present invention are particularly preferably ceramides represented by the following general formula (5) or (6). (I) Natural or natural ceramides represented by the general formula (5), and derivatives thereof (hereinafter referred to as natural ceramides).

[0042]

[Chemical 9]

(In the formula, R ²¹ represents a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 7 to 19 carbon atoms which may be substituted with a hydroxyl group; Z ₁ represents a methylene group or Represents a methine group; X ¹² , X ¹³ and X ¹⁴ each independently represent a hydrogen atom, a hydroxyl group or an acetoxy group;
X ¹⁵ represents a hydrogen atom, and forms an oxo group together with an adjacent oxygen atom (provided that when Z ₁ is a methine group, X 1
^{One of 12} and X ¹³ is a hydrogen atom and the other is absent. X ¹⁴ is absent when X ¹⁵ forms an oxo group. R ²² represents a hydroxymethyl group or an acetoxymethyl group; R ²³ represents a hydrogen atom or has 1 carbon atom.
R 4 is an alkyl group of 4 to 4; R ²⁴ is a linear, branched or cyclic, saturated or unsaturated hydrocarbon group having 5 to 30 carbon atoms which may be substituted by a hydroxyl group, or the alkyl group At the ω-terminal, a linear or branched saturated or unsaturated fatty acid having 8 to 22 carbon atoms, which may be substituted by a hydroxyl group, is ester-bonded, and the broken line portion may be an unsaturated bond. Show good things. )

[0044] Preferably, R ²¹ is 7 to 19 carbon atoms, more preferably a linear alkyl group having 13 to 15 carbon atoms;, R ²⁴
Is a linear alkyl group that may be substituted with a hydroxy group having 9 to 27 carbon atoms or linoleic acid having an ester bond with 9 carbon atoms
The compound which is a linear alkyl group of-27 is mentioned. X ¹⁵ preferably represents a hydrogen atom or forms an oxo group together with an oxygen atom. In particular, R ²⁴ is preferably tricosyl, 1-hydroxypentadecyl, 1-hydroxytricosyl, heptadecyl, 1-hydroxyundecyl, or a nonacosyl group in which linoleic acid is ester-bonded at the ω-position.

Specific examples of natural ceramides include:
Ceramides Type 1 to 7 in which sphingosine, dihydrosphingosine, phytosphingosine or sphingigenin are amidated (for example, J. Lipid Res., 24: 759.
(1983) FIG. 2 and J. Lipid. Res., 35: 2069 (1994) FIG. 4
Porcine and human ceramides mentioned).

[0046]

[Chemical 10]

Furthermore, these N-alkyl compounds (for example, N-
Methyl form) is also included. These may be natural extracts or synthetic products, and commercially available products can be used. These ceramides may be either a natural (D (-) form) optically active substance or a non-natural (L (+) form) optically active substance, and a mixture of a natural type and a non-natural type. May be used. The relative configuration of the above compound may be a natural configuration or a non-natural configuration other than that, or may be a mixture thereof. Especially CERAMIDE1, CERAMIDE2, CERAMIDE3, CERAMIDE5, CERA
Compounds of MIDE6II (above, INCI, 8th Edition) and those represented by the following formula are preferred.

Commercially available natural ceramides include Ceramide I, Ceramide III, Ceramide IIIA and Ce.
ramide IIIB, Ceramide IIIC, Ceramide VI (above,
Cosmo Farm Co., Ltd., Ceramide TIC-001 (Takasago International Co., Ltd.), CERAMIDE II (Quest International Co., Ltd.), DS-C
eramide VI, DS-CLA-Phytoceramide, C6-Phytoceramid
e, DS-ceramide Y3S (manufactured by DOOSAN) and CERAMIDE2 (manufactured by Cederma).

[0049]

[Chemical 11]

(II) Pseudo-type ceramides represented by the following general formula (6).

[0051]

[Chemical 12]

(In the formula, R ²⁵ represents a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 10 to 22 carbon atoms which may be substituted with a hydroxyl group; X ⁴ represents a hydrogen atom; Represents an acetyl group or a glyceryl group; R ²⁶ has 5 to 5 carbon atoms which may be substituted with a hydroxyl group or an amino group.
22 straight chain, branched chain or cyclic saturated or unsaturated hydrocarbon group, or a straight chain having 8 to 22 carbon atoms which may be substituted with a hydroxyl group at the ω terminal of the hydrocarbon group, or Shows a branched chain saturated or unsaturated fatty acid ester-bonded; R ²⁷ represents a hydrogen atom, or an alkyl group having 1 to 8 carbon atoms which may be substituted with a hydroxyalkoxy group, an alkoxy group or an acetoxy group. Indicates a group. ) R ²⁶ is particularly nonyl, tridecyl, pentadecyl, an undecyl group in which linoleic acid is ester-bonded in the ω-position, a pentadecyl group in which linoleic acid is ester-bonded in the ω-position, and 12-hydroxystearic acid is ester-bonded in the ω-position. A pentadecyl group and an undecyl group in which methyl-branched isostearic acid is amide-bonded at the ω-position are preferable. R ²⁷
As the hydroxyalkoxy group or alkoxy group of, those having 1 to 8 carbon atoms are preferable.

As the general formula (6), R ²⁵ is a hexadecyl group, X ⁴ is a hydrogen atom, R ²⁶ is a pentadecyl group, R ²⁷ is a hydroxyethyl group; R ²⁵ is a hexadecyl group, X is
⁴ is a hydrogen atom, R ²⁶ is a nonyl group, R ²⁷ is a hydroxyethyl group; or R ²⁵ is a hexadecyl group, X ⁴ is a glyceryl group, R ²⁶ is a tridecyl group, and R ²⁷ is a 3-methoxypropyl group. Ceramides are preferable, and in the general formula (6), R ²⁵ is a hexadecyl group, X ⁴ is a hydrogen atom, R ²⁶ is a pentadecyl group, and R ²⁷ is a hydroxyethyl group.

Two or more kinds of component (C) may be used in combination.
The content of the component (C) in the external preparation for skin of the present invention is 50% by weight or less, more preferably 0.01 to 20% by weight, particularly 0.01 to 20% by weight.
It is preferably 10% by weight.

Weight ratio of the components (A), (B) and (C) contained in the external preparation for skin of the present invention ((A) +
Although (B)) / (C) is 0.0001 or more, 0.001 to 10, particularly 0.01 to 6, is preferable in terms of stability.

The external preparation for skin of the present invention does not contain acrylic acid polymer (carboxyvinyl polymer) and phospholipid (lecithin) from the viewpoint of storage stability, but the component (A),
Other anionic compounds can be added as long as the emulsification with (B), (C) and water is completed and after cooling to room temperature.

The combination of the components (A), (B) and (C) used in the external preparation for skin of the present invention is preferably a combination of the respective components, and particularly the component (A) is represented by the general formula (3). Then, the component (C) is represented by the general formula
When the component (A) of the formula (5) is the general formula (4), the component (C) is preferably combined with the general formula (6). In particular, COR ¹⁰ bonded to nitrogen of the component (C) general formula (2) is converted into H.
It is preferable from the viewpoint of stability and effect that the compound substituted with is used as the general formula (1) of the component (A).

The external preparation for skin of the present invention is produced as an emulsion of these components (A), (B) and (C) and water. When an alcohol is further added, it is represented by the general formula (1). Sphingosines, ceramides and components (B)
It is preferable because the liquid crystal structure formed by the acid can be stably maintained and the stability is further improved.

Examples of alcohols include ethyl alcohol, glycerin, diglycerin, polyglycerin,
Examples thereof include polyhydric alcohols such as sorbitol, propylene glycol, dipropylene glycol, 1,3-butanediol, polyoxyethylene methyl glucoside and polyethylene glycol. Especially glycerin, 1,3-butanediol, polyoxyethylene methyl glucoside,
Polyethylene glycol, ethyl alcohol and the like are preferable. Two or more alcohols may be used in combination. The content of alcohols in the external preparation for skin of the present invention is 50% by weight.
It is particularly preferable that the content be 0.01 to 30% by weight.

Furthermore, the external preparation for skin of the present invention is preferably added with a higher alcohol, a fluorinated oil or a silicone because the emulsion stability and the feeling of use are improved. As the higher alcohol, stearyl alcohol, cetyl alcohol, isostearyl alcohol, lanolin acetate acetate, polyoxyethylene lanolin alcohol acetate, hydrogenated lanolin alcohol, cetostearyl alcohol,
Examples thereof include batyl alcohol and lanolin alcohol. Particularly, stearyl alcohol, cetyl alcohol, batyl alcohol and the like are preferable. Two or more kinds of these higher alcohols may be used in combination. The content of the higher alcohol in the external preparation for skin of the present invention is 10% by weight or less, particularly 0.0
It is preferably from 1 to 5% by weight.

As the fluorine-based oil agent, the following general formula (7) is used.

[0062]

[Chemical 13]

(In the formula, R ²⁸ may be a linear or branched alkyl group having 2 to 30 carbon atoms, n is an integer of 1 or 2, and Rf may have a hydrogen atom at a terminal carbon atom. Carbon number 3 ~
20 is a linear or branched fluorocarbon group).

In the general formula (7), R ²⁸ has 6 carbon atoms.
It is preferably an alkyl group of -18, particularly preferably a hexyl group, an octyl group, a decyl group and a dodecyl group. Further, the group represented by Rf is preferably a fluorine-substituted alkyl group having a chain length of 6 to 12 carbon atoms. For example, a linear or branched perfluoropropyl group, perfluorobutyl group, perfluoropentyl group, perfluorohexyl group, perfluoroheptyl group, perfluorooctyl group, perfluorononyl group, perfluorodecyl group,
Perfluoroundecyl group, 1,1,2,2,3,3,3
4,4-octafluorobutyl group, 1,1,2,2,
3,3,4,4,5,5-decafluoropentyl group,
1,1,2,2,3,3,4,4,5,5,6,6-dodecafluorohexyl group, 1,1,2,2,3,3,3
4,4,5,5,6,6,7,7-tetradecafluoroheptyl group, 1,1,2,2,3,3,4,4,5
5,6,6,7,7,8,8-hexadecafluorooctyl group can be mentioned. In particular, a perfluorohexyl group,
Perfluorooctyl group, perfluorodecyl group, 1,
1,2,2,3,3,4,4,5,5,6,6-dodecafluorohexyl group, 1,1,2,2,3,3,4
A 4,5,5,6,6,7,7,8,8-hexadecafluorooctyl group and the like are preferable. Two or more fluorine-based oil agents may be used in combination. The content of the fluorinated oil agent in the external preparation for skin of the present invention is preferably 50% by weight or less, particularly preferably 0.01 to 10% by weight.

Examples of silicone include cyclic dimethylpolysiloxane type, chain dimethylpolysiloxane type, high molecular weight dimethylsiloxane, methylphenylpolysiloxane type, amino-modified silicone, carboxy-modified silicone, alkyl-modified silicone, polyether-modified silicone, Examples of the modified silicone include alcohol-modified silicone and fluorine-modified silicone. Two or more kinds of silicone may be used in combination. The content of silicone in the external preparation for skin of the present invention is 50% by weight or less, particularly 0.01 to 10%.
It is preferably wt%.

In the external preparation for skin of the present invention, in addition to these components, components used in the external preparation for skin can be appropriately used, if necessary. For example, humectants such as glycine betaine, xylitol, trehalose, urea, neutral amino acids, basic amino acids; water-soluble thickeners such as xanthan gum, hydroxyethyl cellulose, methyl cellulose, hydroxypropyl guar gum; squalane, liquid paraffin, isotridecyl isononanoate, Oil agents such as cholesterol, phytosterols, higher fatty acids, cholesteryl isostearate; drug agents such as allantoin and tocopherol acetate; cationic surfactants such as dimethyl distearyl ammonium chloride; polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ethers, etc. Nonionic surfactant; Cellulose powder, Nylon powder, Crosslinked silicone powder, Crosslinked methylpolysiloxane, Porous cellulose powder, Porous nylon Organic powders such as silica powder; inorganic powders such as anhydrous silica, zinc oxide, and titanium oxide; other cooling agents such as menthol and camphor; plant extracts, pH buffers, antioxidants, UV absorbers, preservatives , Fragrances, germicides, pigments and the like.

The external preparation for skin of the present invention comprises components (A) to
It is produced by mixing and emulsifying (C), water and appropriately used components such as higher alcohol, fluorine-based oil agent, silicone, water-soluble polymer and liquid oil. This emulsion is produced in a transparent, translucent or cloudy state. The term "transparent" or "translucent" as used herein means that the turbidity (kaolin standard: purified kaolin 1 ng / 1 liter of water turbidity is 1 ppm) measured by an integrating sphere photoelectric scattering photometer is 1 to 1500 ppm. Content weight ratio of components (A), (B) and (C) ((A) +
When (B)) / (C) is 0.2 or more, a transparent or translucent emulsion is obtained, and when it is less than 0.2, the emulsion becomes cloudy. The average particle size of the oil droplets of the emulsion is appropriately produced in the range of 3 nm to 200 μm according to the appearance and application, but from the viewpoint of the stability of the appearance of the emulsion, 5 nm to 50 μm, particularly 5 nm to 1
It is preferably 0 μm. The average particle size is measured by a dynamic light scattering particle size distribution measuring device (for example, HORIBA LB-500) or a laser diffraction / scattering particle size distribution measuring device (for example, HORIBA
LA-920).

In the present invention, the viscosity of the emulsion depends on the blending amount of solid lipid such as ceramides or other components.
It is also affected by the manufacturing method. In a creamy composition containing 10% by weight or more of the total oil phase excluding silicone oil, when the solid lipid is 30% by weight or more of the total oil phase, the composition is approximately 20,000 mPa · s or more. Feeling of use,
In terms of good spreadability, the viscosity of the present invention is 200.
It is preferable that the lotion or emulsion is 00 mPa · s or less.

The external preparation for skin of the present invention comprises cosmetics, pharmaceuticals,
It is preferably used as a bathing agent, a cleansing agent, and a scalp care agent, and especially a cosmetic, for example, a semitransparent lotion, a semitransparent emulsion,
It is preferably used as a moisturizing beauty essence, a whitening beauty essence, a moisturizing emulsion and the like.

[0070]

EXAMPLES Examples 1-21 and Comparative Examples 1-4 The external skin preparations having the compositions shown in Tables 1 to 5 were produced. Compounds used: Pseudo-type sphingosine (i); R in formula (4)¹⁷Is isos
Thearyl group, X^FourIs a hydrogen atom, a is 2 and R is¹⁹But
1,1-dimethyl-2-hydroxyethyl group, R ¹⁸But water
Those that are elementary atoms. Pseudo-type sphingosine (ii); R in formula (4)¹⁷Is isos
Thearyl group, X^FourIs a hydrogen atom, a is 2 and R is¹⁸But
2-hydroxyethyl group, R¹⁹Is a hydrogen atom. Pseudo-type sphingosine (iii); R in formula (4)¹⁷Is iso
Stearyl group, X^FourIs a hydrogen atom, a is 2 and R is¹⁸
Is a 2- (2-hydroxyethoxy) ethyl group, R¹⁹But water
Those that are elementary atoms. Pseudo-type sphingosine (iv); R in formula (4)¹⁷Is isos
Thearyl group, X^FourIs a hydrogen atom, a is 2 and R is¹⁸But
1,1-bis (hydroxymethyl) ethyl group, R ¹⁹But water
Those that are elementary atoms. Pseudo-type ceramides (i); R in formula (6)^{twenty five}Is hexadeci
Lu group, X^FourIs a hydrogen atom, R²⁶Is a pentadecyl group, R²⁷But
Those that are hydroxyethyl groups. Pseudo-type ceramides (ii); R in formula (6)^{twenty five}Is hexadeci
Lu group, X^FourIs a hydrogen atom, R²⁶Is a nonyl group, R²⁷Is hydro
Those that are xyethyl groups.

(Examples 1 to 4) Production method: A to C and 80 to 9 of 13-21 of other components
Stir to heat at 0 ℃ to dissolve and stir (300r / mi
While n), a component obtained by heating and dissolving a part of component B and water was added. After the addition, while stirring, the mixture was subjected to a homomixer (9000 r / min) as needed, cooled to 30 to 40 ° C., and then the components of 22 to 29 were added and mixed. The L-glutamic acid aqueous solution of Comparative Example 4 was added after cooling.

Stability evaluation: 50 ° C., room temperature (25 ° C.), −
The appearance after standing at 5 ° C. for 1 week was visually evaluated. Evaluation: Good stability at any temperature, emulsion separation,
No precipitation was observed after crystallization. Evaluation x: unstable at any temperature, separation of emulsification or precipitation of crystals was observed.

[0073]

[Table 1]

For Examples 5 to 10, external preparations for skin were produced in the same manner as in Examples 1 to 4 and stability was evaluated.

[0075]

[Table 2]

For Examples 11 to 17, external preparations for skin were produced in the same manner as in Examples 1 to 4, and the stability was evaluated.

[0077]

[Table 3]

For Examples 18 to 21, external preparations for skin were produced in the same manner as in Examples 1 to 4, and the stability was evaluated.

[0079]

[Table 4]

Regarding Comparative Examples 1 to 4, Examples 1 to 1
A skin external preparation was produced in the same manner as in 4, and the stability was evaluated.

[0081]

[Table 5]

The external preparations for skin of the present invention were all stable.

[0083]

EFFECTS OF THE INVENTION The external preparation for skin of the present invention does not cause ceramides to be separated and precipitated without using a surfactant, phospholipid or the like,
A product with excellent storage stability and a transparent to cloudy appearance can be easily obtained by adjusting the components.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 31/164 A61K 31/164 31/194 31/194 31/198 31/198 33/42 33/42 A61P 17/16 A61P 17/16 43/00 111 43/00 111 (72) Inventor Hidehiro Nagasawa 2-1-3 Fumika, Sumida-ku, Tokyo Kao Corporation Stock Research Institute (72) Inventor Tomoyuki Yamamoto Sumida-ku, Tokyo Bunhana 2-1-3 F-term in the Kao Institute of Stock Company (reference) 4C076 AA16 BB31 CC19 DD38 FF16 4C083 AA032 AA112 AB011 AB012 AB102 AC022 AC072 AC102 AC122 AC172 AC182 AC231 AC292 AC432 AC482 AC541 AC542 AC582 AC641 AC642 AC712 AC782 AD042 AD152 AD152 AD1522 AD282 AD352 AD492 AD662 CC02 CC05 DD31 EE12 4C086 AA01 AA02 HA19 MA03 MA04 MA63 NA14 ZA89 ZC02 4C206 AA01 AA02 DA36 FA03 GA01 GA03 GA04 GA26 MA03 MA04 MA83 NA14 ZA89 ZC02

Claims (3)

[Claims] 1. The following components (A), (B) and (C): (A) a sphingosine represented by the general formula (1), [Chemical 1] (In the formula, R¹Is a hydroxyl group, a carbonyl group or
A linear group having 4 to 30 carbon atoms, which may be substituted by
A branched or cyclic saturated or unsaturated hydrocarbon group; Y
Is either a methylene group, a methine group or an oxygen atom.
Yes; X¹, X², And X³Are independently hydrogen atom and hydr
Roxyl group or acetoxy group, X^FourIs hydrogen
Acid presenting or adjoining a child, an acetyl group or a glyceryl group
It forms an oxo group together with the elementary atom (provided that Y is
When it is a chin group, X¹And X²One of is a hydrogen atom
And the other does not exist. X^FourForm an oxo group,
X³Does not exist. ); R²And R³Are each independently hydrogen
Atom, hydroxyl group, hydroxymethyl group or aceto
A xymethyl group; a R's each independently represent a hydrogen atom
Or amidino group, hydroxyl group, hydroxy group
Selected from alkoxy group, alkoxy group and acetoxy group
A linear chain having 1 to 8 carbon atoms which may have a substituent
Represents a branched chain saturated or unsaturated hydrocarbon group; a represents 2
Or the number of 3 is shown; the broken line part may be an unsaturated bond
Indicates that. ) (B) an inorganic acid or an organic acid having 5 or less carbon atoms, (C) Ceramides represented by the general formula (2) [Chemical 2] (In the formula, R⁷Is a hydroxyl group, a carbonyl group or
A linear group having 4 to 30 carbon atoms, which may be substituted by
A branched or cyclic saturated or unsaturated hydrocarbon group; Z
Is either a methylene group, a methine group or an oxygen atom.
Yes; X^Five, X⁶And X ⁷Are each independently a hydrogen atom, hydro
Xyl group or acetoxy group, X^FourIs a hydrogen atom,
An oxygen source showing or adjoining an acetyl group or glyceryl group
Forms an oxo group together with the child (however, Z is methine
When it is base, X^FiveAnd X⁶One of is a hydrogen atom and the other is
There is no one. X^FourWhen X forms an oxo group, X⁷Is
Not present. ); R⁸And R⁹Are each independently a hydrogen atom,
Droxyl group, hydroxymethyl group, or acetoxime
Represents a chill group; R^TenIs a hydroxyl group, a carbonyl group or
Is an ether group in the main chain, which may be substituted with an amino group.
, Which may have an ester bond or an amide bond
Linear, branched or cyclic saturated or unsaturated with a prime number of 5 to 60
Represents a hydrocarbon group of R;¹¹Represents a hydrogen atom or hydro
Xyl group, hydroxyalkoxy group, alkoxy group and
It may have a substituent selected from an acetoxy group,
Straight-chain or branched saturated or unsaturated carbon having 1 to 8 total carbon atoms
Indicates a hydrogen fluoride group; the broken line part may be an unsaturated bond.
And indicates. ) Containing the weight of the emulsion
When the ratio ((A) + (B)) / (C) is 0.0001 or more
Yes, does not contain acrylic acid polymers or phospholipids
External skin preparation. 2. The component (B) is 1 mol / L at 25 ° C.
The external preparation for skin according to claim 1, wherein the aqueous solution has a pH of 1 or more and less than 7 and forms a salt with the component (A) in the external preparation for skin. 3. ((A) + (B)) / (C) is 0.00
The external preparation for skin according to claim 1 or 2, which is an emulsion having a viscosity of 1 to 10 and a viscosity of 20000 mPa · s or less.