JPS63192703A - External agent for skin - Google Patents

Abstract

PURPOSE:To obtain an external agent for skin effective in improving water- retaining capacity of corneum and ameliorating chapped skin, by combining a ceramide or a substance having analogous structure with a lipid existing between cuticle cells and, preferably, adding a surfactant to the combined product. CONSTITUTION:The objective external agent for skin can be produced by compounding (A) one or more ceramides of formula I (R<1> and R<2> are 10-26C straight or branched chain saturated or unsaturated hydrocarbon group which may be substituted with one or more OH groups) or a substance having analogous structure [e.g. novel amide derivative of formula II (R<3> and R<4> are one of R<1> and R<2>)] and (B) one or more compounds selected from cholesterol, cholesterol fatty acid ester, fatty acid, triglyceride, cerebroside and phospholipid preferably at a weight ratio of 8:2-2:8. It is effective to add a surfactant, especially a nonionic surfactant to the agent.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an external skin preparation, and more particularly to an external skin preparation that can improve the moisture retention of the stratum corneum and improve rough skin.

[Conventional technology]

It has been known that the moisture in the stratum corneum is important for K, which moisturizes and softens the skin. The retention of moisture is said to be due to water-soluble components contained in the stratum corneum, such as free amino acids, organic acids, urea, or inorganic ions, and these substances may be used alone or in combination in medicated skin preparations. Alternatively, it is used in cosmetics to improve or prevent rough skin.

In addition, many other moisturizing substances that have a high affinity for water have been developed and are used for similar purposes.

[Problem that the invention seeks to solve]

However, when these moisturizing substances are applied to the skin, their action is to be on the stratum corneum and supply moisture to the stratum corneum, and their effect is temporary.
It was not intended to fundamentally improve the water retention ability of the stratum corneum and essentially prevent or cure all skin roughness.

[Means for solving problems]

Under these circumstances, the present inventors conducted intensive research focusing on interkeratinocyte lipids in order to solve the above-mentioned problems, and found that a combination of ceramide or a similar structural substance and lipids existing between corneocytes. The present invention was completed based on the discovery that the above mixture has the effect of fundamentally improving the water retention ability of the stratum corneum, and that the effect can be further increased by using a surfactant in combination with the above mixture.

That is, the present invention uses the following components (A) and (B) (4) general formula (1) (wherein R1 and R1 are straight chain or carbon atoms having 10 to 26 carbon atoms which may be substituted with one or more hydroxyl groups) One or more ceramides or similar structural substances represented by (representing branched saturated or unsaturated hydrocarbon groups); (B) cholesterol, cholesterol fatty M esters, fatty acids, triglycerides, cereprosides or phospholipids; The present invention provides an external preparation for skin containing one or more of the following.

Ceramide (1) used in the present invention is a known metal compound. In addition, the similar structural substance is a lipid derivative that has two long-chain hydrocarbon groups and an OH group and an amide group between them, and the molecule can assume a uniplanar conformation. say. Examples of such similar structural substances include amide derivatives represented by the following general formula (1).

R”-0-CM.

CH, CH, OH (wherein, Rs is a straight chain or branched saturated or unsaturated hydrocarbon group having 10 to 26 carbon atoms, and R4 is a straight chain or branched saturated or unsaturated hydrocarbon group having 9 to 26 carbon atoms)
Although this amide derivative (1) is a new compound, it can be prepared by known methods [for example, ? Risch Sharnal Op Chemistry (Po1.J, Ch.m,);
It can be manufactured according to JP-A-54-117421, JP-A-54-144308, and JP-A-54-147937. That is, it can be produced by reacting compound (1) obtained from glycisole ether and ethanolamine with t-fatty acid methyl ester according to the reaction formula shown below.

(In the formula, R1 and R4 are the same as above.) As the cholesterol, one represented by the following formula (ff) is most preferable, but any derivative can be used as long as the hydroxyl group at the 3-position remains. .

The cholesterol fatty acid ester is represented by formula (V) (wherein R1 represents a straight or branched saturated or unsaturated hydrocarbon group having 1 to 25 carbon atoms which may be substituted with one or more hydroxyl groups). The one shown is most preferred, but any derivative in which the 3-position ester group remains can be used.

The fatty acid has the general formula (■) R'-COOH (Vl) (where R6 is a straight or branched saturated or unsaturated hydrocarbon having 1 to 25 carbon atoms which may be substituted with one or more hydroxyl groups). (indicating a group) can be used, but linear saturated or unsaturated fatty acids having 14 to 18 carbon atoms are most suitable.

The triglyceride has the general formula (■) (where Hl, Ha, and R1 represent a straight or branched saturated or unsaturated hydrocarbon group having 1 to 25 carbon atoms, which may be substituted with one or more hydroxyl groups). ) can be used.

Celeproside is a complex lipid in which sugar is added to the ceramide of the formula (1), and has the general formula (■)R''-CH-0X (wherein, X represents a substance such as glucose or lactose)
1, R1 is the same as above).

Phospholipids can be broadly classified into glycerophospholipids, which are glycerin derivatives, and sphingophospholipids, which are ceramide derivatives, and any of these can be used in the present invention.

The blending ratio of component (A) and component (B) in the external skin preparation of the present invention is preferably 8=2 to 2:8 in terms of weight ratio. To blend these, it is preferable to mix both in the above ratio, heat and melt, then cool to form a paste or solid, which is then added to the other ingredients, but it is also preferable to add each separately. Good too.

The amount of the mixture of component (A) and component (B) in the skin preparation of the present invention is not particularly limited, but in the case of an emulsion-type skin preparation, it is usually 0.01 to 60% by weight of the total composition. (hereinafter simply expressed as %), preferably 0.1 to 30%, and in the case of oily skin preparations based on liquid hydrocarbons such as squalane, 1 to 90%, especially 5 to 50%. preferable.

As the surfactant used in combination to further increase the effects of the present invention, any of nonionic surfactants, anionic surfactants, and amphoteric surfactants can be used, but especially nonionic surfactants is suitable.

What are some examples of nonionic surfactants? Lioxyethylene alkyl ether,? Lyoxyethylene alkyl phenyl ether, breaking oxyethylene fatty acid ester, sorbitan fatty acid ester,? Examples include lyoxyethylene sorbitan fatty acid ester, fatty acid monoglyceride, and glyceryl ether. Among them, the following general formula (
W) Glyceryl ether represented by H (in the formula, Blo represents an alkyl group having 8 to 24 carbon atoms), in which R1° is the following formula <
X is particularly preferred.

The blending amount of the surfactant is preferably 0.01 to 20%, particularly 0.01 to 5% of the total composition.

The skin external preparations of the present invention are broadly classified into medicated skin external preparations and cosmetics in terms of their usage forms.

Examples of medicated skin external preparations include various ointments containing medicinal ingredients.

The ointment may be one based on an oily base, or one based on an emulsion base of oil/water or water/oil-deaf. The oily base is not limited in percentage and includes, for example, vegetable oils, animal oils, synthetic oils, fatty acids, natural or synthetic glycerides, and the like. There are no particular limitations on the medicinal ingredients, and for example, analgesic and antiinflammatory agents, antipruritic agents, sterilizing disinfectants, astringents, emollients, hormonal agents, and the like can be used as appropriate.

In addition, when used as a cosmetic, in addition to the essential ingredients, oils, moisturizers, ultraviolet absorbers, alcohols, chelating agents, PH adjusters, etc. that are commonly used as cosmetic ingredients,
Preservatives, thickeners, pigments, fragrances, etc. can be blended in any combination.

Cosmetics can be used in various forms, such as water/oil, oil/water type emulsified cosmetics, creams, cosmetic emulsions, lotions, oil-based cosmetics, lipsticks, foundations, skin cleansers, hair tonics, hair styling products, hair tonics, etc. It can be used as a skin cosmetic such as a hair growth agent.

[Effect]

Although the details of the mechanism of action of the mixture of component (4) and component (B) in the topical skin preparation of the present invention have not been completely elucidated, it builds a lipid bilayer with water between corneocytes and It is thought that it exerts a moisture retention function.

〔Effect of the invention〕

Since the skin external preparation of the present invention contains a mixture of ingredients having such an action (a mixture of Shu and ingredient (B)), it can exhibit excellent improvement and preventive effects against rough skin.

〔Example〕

Next, reference examples and examples will be given and explained.

Reference Example I N-(2-hydroxy-3-hexatesiloxyzolobyl)-N-2-hydroxyethylhexadecanamide [Formula (
1) at h, 13=++(!.Ho, R': C
! , H, ) Synthesis of (IJL): Ethanolamine 1637f (2
6,8 morph and 327 t (7,11 mol) of ethanol in a gold pot, heated to 80°C under nitrogen atmosphere and stirred,
This was added to hexadecyl glycisol ether 400f (1,
(34 mol) was added dropwise over t-3 hours. After the dropwise addition was completed, the mixture was heated and stirred for 30 minutes under the same conditions, and then the distillation apparatus was turned on and ethanol and unreacted ethanolamine were distilled off under reduced pressure (79-81'C/20 Torr).
)did. While heating and stirring at 80°C/20 Torr,
To this, 3613 f (L34 mol) of methyl hexadecanoate was added dropwise over 3 hours. After dropping 1 C, the mixture was further heated and stirred for 1 hour under the same conditions to obtain pale yellow crude product 801f. By recrystallizing this once from hexane and twice from ethanol,
The target compound (1m) e 49 t (yield 81%) was obtained as a colorless powder.

Example 1 Preparation of a mixture of component (A) and component (B): Compound (Im
), 60% by weight of cholesterol [formula (ff):)
Weigh into a glass Nezoro sample bottle so that the amount is 40% by weight. Heat the sample bottle to 150°C using a heating block and other devices. Heat it up (I
When m) and cholesterol are completely dissolved, the heating is finished and the mixture is left to cool in the air to obtain a paste-like mixture.

Example 2 A skin external preparation prepared by adding and blending the mixture obtained in Example 1 to petrolatum so that (Im) was 15% by weight and cholesterol was 10% by weight (invention product 1), the above mixture was added to petrolatum. (Ia) was added so that the cholesterol content was 10% by weight, and 4% by weight of glyceryl nitride (Formula (R1 @ Formula (X))) was added. Using the skin external preparation (invention product 2) prepared by the above method and vaseline (control), the skin contactance and skin roughness were evaluated according to the following method.The results are shown in Table 1.

(Test Method) Ten women between the ages of 20 and 50 who suffer from rough skin on their cheeks during the winter were used as subjects, and different sunglasses were applied to the left and right cheeks once a day for two weeks. The next day after the two-week application was completed, the following tests were conducted.

(1) Skin conductance After washing the face with warm water at 37°C and resting for 20 minutes in a room with a temperature of 20°C and humidity of 40%, the water content of the stratum corneum was measured using a skin conductance meter (manufactured by IBS). .

The smaller the conductance value, the rougher the skin;
Below, you can see the rough skin. On the other hand, if this value is 20 or more, skin roughness is hardly observed.

(2) Skin roughness score Skin roughness was observed with the naked eye and judged according to the following criteria. Scores are expressed as standard deviation above the mean.

(Results) Table 1 Example 3 Compound (1a), cholesterol indicated by the formula (chamber), and stearic acid [Formula (■), R cap = CIT"am] as shown in Table 2. A blended oil-in-water emulsion cosmetic was produced and evaluated for skin conductance and skin roughness using the same method as in Example 2. The results are shown in Table 3.

Table 2 (% by weight) Table 3 Example 4 Ceramide represented by formula (1) [bovine brain ceramide (manufactured by Funakoshi Pharmaceutical Co., Ltd.)], cholesterol instearate [R5 in formula (Y) is the formula (X)], stearic acid [formula (Vl) with R@”C+yHsj]
, 2-ethylhexanoic acid triglyceride [R in formula (■)
'=l'=R''=CH, -(CH,), -C)i
-CH] are shown in Table 4. CH, -CH.

Table 5 shows the results of six evaluations of skin impedance and skin roughness K using the same method as in Example 2.

Table 4 Table 5 Example 5 Skin preparation (oil-based ointment) Composition> (1) Vaseline 30.0 (
Weight%) (2) Ceramide (I)
To,.

(3) Cholesterol 3.0 (
4) Cholesterol isostearate) ZO (5) Stearic acid 4.0 (6) Olive oil
Amount that makes the whole 100 (7) t-
Menthol 0.3 (8) Camphor 0.3 Production method> Add 1 to the mixed and heated mixture of (1), (7) to (8).
Separately, mix (2) to (6) and add the heated and dissolved mixture,
An oily ointment was prepared by uniformly mixing and cooling to around room temperature.

Example 6 Cosmetic (emulsion) Composition> Oil phase components: Macadamian nut oil zO (wt%) squalane &0 stearic acid 1.0 compound (1 m
) 1.0 soy phospholipids
0.5 glucocereproside (bovine brain extract)
0.5 Monostearate Lupitan 0.5P
OE (60) Hydrogenated castor oil 1.0 Water phase components: Glycerin 1.0 Propylene glycol 1.0 Methyl-9-Lapen
0.3 fragrance
0.1 Purified water total'ft1
OO production method〉 Mix the oil phase components, heat and dissolve and keep at 70°C. The aqueous phase components are similarly heated and mixed at 70"C, and the aforementioned oil phase is added to this aqueous phase component and emulsified using an emulsifier. The emulsion is cooled to a final temperature of 30"C using a heat exchanger. A milky lotion was prepared by filling a container.

that's all

Claims (1)

[Claims] 1. The following components (A) and (B), (A) General formula (I) ▲There are numerical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R^1 and R^ 2 represents a straight chain or branched chain saturated or unsaturated hydrocarbon group having 10 to 26 carbon atoms which may be substituted with one or more hydroxyl groups) or one or two of its similar structural substances. (B) A skin external preparation characterized by containing one or more of cholesterol, cholesterol fatty acid ester, fatty acid, triglyceride, cerebroside, or phospholipid. 2. The blending ratio of component (A) and component (B) is 8: by weight.
The skin external preparation according to claim 1, wherein the ratio is 2 to 2:8. 3. The skin external preparation according to claim 1, further comprising a surfactant.