JPH09241144A - Ceramide derivative and cosmetic containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new compound, having improving activity against rough skin, capable of improving humectant function and useful as a cosmetic component for skin external composition, etc., free from skin irritation. SOLUTION: A ceramide derivative of formula I or formula II R1 is an aliphatic hydrocarbon or YO(Cd He ) [Y is formula Ill (Z is hydroxy, etc.; (f) is 12-20; (g) is 20-40; (h) is 0-4); (d) is 8-50; (e) is 10-100]; R2 is an aliphatic hydrocarbon; A is CH2 , CH2 O, CH=CH, etc.; Hs is XCHCOOH (X is H or an aliphatic hydrocarbon), etc.; (i) is 1, 2}. The compound is obtained by introducing an eliminable group at the α-position of a carboxylic acid, protecting the carboxyl group, etherifying the carboxylic acid derivative with ceramide and subsequently purifying the reaction product. The ceramide derivative can reduce characteristic irritative feeling without losing the activity of hydroxycarboxylic acid.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a ceramide derivative having a function of improving skin roughness and a function of improving moisturizing ability and effective when blended in a cosmetic such as a composition for external use on skin, and a cosmetic comprising the ceramide derivative. .

[0002]

BACKGROUND ART Hydroxycarboxylic acid has keratin exfoliating action, keratin turnover promoting action, skin cell regeneration promoting action, wound healing action and the like, and is known to have an effect of improving skin aging such as fine wrinkles. (JP-A-63-16
6837). It is generally understood that ceramides reside within the intercellular lipid lamella of the corneum and play an important role in the development and retention of the skin's permeability barrier. Various ceramides or substances closely related thereto are disclosed as components of the skin protectant composition. For example, EP 097059 discloses the major role of ω-linoleoyl ceramides in the water barrier of the skin and describes the synthesis and application of such ω-substituted ceramide skin protectants. Similarly, British Patent No. 2,178,312,
No. 2,213,723 discloses the use of natural ceramide extracted from the skin in topical products and EP 227944 discloses synthetic analogues of ceramide.

[0003]

However, hydroxycarboxylic acid generally needs to be used in an acidic state in order to exert its effect, and since it causes skin irritation when used at a high concentration, it is necessary to use it at a concentration that does not cause irritation. It had to be used, and it was difficult to fully demonstrate its effectiveness.

The present invention has been made in view of the above circumstances, and an object thereof is to provide a novel compound capable of exhibiting the same effectiveness as a hydroxycarboxylic acid without causing skin irritation, and a cosmetic containing the compound. I am trying.

[0005]

The invention according to claim 1 of the present invention is represented by the general formula (1)

Embedded image Alternatively, the general formula (2)

Embedded image [However, R1 straight chain having 8 to 30 carbon atoms, branched, aliphatic hydrocarbon group not Yusuke or have a hydroxyl group, saturated or unsaturated or _{Y-O- (C d H e} ), - a is , Y is the formula (3)

Embedded image (Where Z is a hydroxyl group or epoxy oxygen, d
Is an integer of 8 to 50, e is an integer of 10 to 100, and f is 12
~ 20 integer, g is 20-40 integer, h is 0 or 1
R2 is an aliphatic hydrocarbon group having or not having a linear, branched, saturated or unsaturated hydroxyl group having 8 to 30 carbon atoms; A
Is _{-CH 2 -, - CH 2 O} -, - CH = CH -, - CH
(O · HS)-or formula (4)

Embedded image HS is the formula (5), the formula (6)

Embedded image

Embedded image (Here, X is hydrogen or an aliphatic hydrocarbon group having or not having a linear, branched, saturated or unsaturated hydroxyl group having 1 to 30 carbon atoms, a is an integer of 0 to 9, and b is 1 ~
At least one α-hydroxy acid residue selected from the group consisting of 9), or one of them is H—; i is 1 or 2.].

The invention according to claim 2 is a cosmetic characterized in that it contains at least one ceramide derivative according to claim 1 as an active ingredient.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The ceramide derivative according to the present invention is
It is a novel compound represented by the general formula (1) or (2). This compound has a structure in which a ceramide or a ceramide analogue and an α-hydroxycarboxylic acid are ether-bonded. As the ceramide, various natural ceramides shown in Table 1 and synthetic ceramides represented by the following general formula (7) are known.

[0008]

[Table 1]

[0009]

Embedded image

[Wherein R 1 is an aliphatic hydrocarbon group having 8 to 30 carbon atoms, with or without a linear, branched, saturated or unsaturated hydroxyl group, or YO- (C
_d H _e) - a and, Y is the formula (8)

[0011]

Embedded image

(Where Z is a hydroxyl group or epoxy oxygen, d is an integer of 8 to 50, e is an integer of 10 to 100, f is an integer of 12 to 20, g is an integer of 20 to 40, and h is
Is 0 or an integer of 1 to 4);
R2 is a straight chain of 8 to 30 carbon atoms, branched, saturated or having a hydroxyl group of the unsaturated or have not aliphatic hydrocarbon group; A is _{-CH 2 -, - CH 2 O-} , or - CH
= A CH-; B and C are -H, -CH ₂ OH, or -CH ₂ -CH ₂ OH; represented by]

The ceramide analogue has a structure similar to that of the natural ceramide or the synthetic ceramide shown in Table 1 above and is highly safe to the skin, and has a moisturizing effect and an emollient effect similar to those of the natural ceramide and the synthetic ceramide. I have.

The hydroxycarboxylic acid to be bound to the ceramide or ceramide analogue may be any organic acid having at least one hydroxyl group and one carboxyl group, and has a straight carbon chain or a branched carbon chain. Those having a ring, those having a saturated bond, those having a unsaturated bond, and the like are used. The following are mentioned as a specific example of hydroxycarboxylic acid. As the one having 2 carbon atoms, glycolic acid can be mentioned. Examples of those having 3 carbon atoms include lactic acid, 3-hydroxypropanoic acid, and 2,3-hydroxypropanoic acid. As those having 4 carbon atoms, methyl lactic acid, malic acid, tartaric acid, oxalacetic acid,
2-hydroxybutanoic acid, 3-hydroxybutanoic acid, 4
-Hydroxybutanoic acid, 3-hydroxy-2-methylpropanoic acid, 2-hydroxy-3-butenoic acid.

As the one having 5 carbon atoms, itertartaric acid,
Examples thereof include itamaric acid, 2-hydroxypentanoic acid, 2,3-dihydroxypentanoic acid, 2-hydroxy-3-methylbutanoic acid, hydroxypivalic acid, and 2-hydroxy-2-methylbutanedicarboxylic acid. Examples of those having 6 carbon atoms include citric acid, isocitric acid, galacturonic acid, 2-keto-galactonic acid, 2-hydroxyhexanoic acid, and 2-hydroxy-2-methylglutaric acid.

As those having 7 carbon atoms, salicylic acid,
Examples include gallic acid, quinic acid, and 2-hydroxyheptanoic acid. As those having 8 carbon atoms, mandelic acid, 4-methylsalicylic acid, 3-methoxysalicylic acid, 2-hydroxyoctanoic acid, 2-hydroxyphenylacetic acid, 3,4
-Dihydroxyphenylacetic acid and 4-hydroxyphthalic acid are mentioned. Examples of those having 9 or more carbon atoms include 3-phenyllactic acid, 3-hydroxy-4-methoxymandelic acid, 4-hydroxydecanoic acid, 12-hydroxydodecanoic acid, 4-hydroxy-2,2-diphenylbutanoic acid and the like. Can be mentioned.

Of these, the number of carbon atoms is preferably 2-8.
Of these, and more preferably glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, isocitric acid, and salicylic acid.

These hydroxycarboxylic acids can be obtained by various methods such as chemical synthesis, extraction from natural products and fermentation. The extract or the like from a natural product includes components other than hydroxycarboxylic acid and its salt, but the extract or the like can be used as it is without particular separation and purification. Specific examples of the extraction from natural products include extraction from plants such as aloe (aloe vera, yellowtail aloe, etc.), sugar cane, citrus fruits, cowberry, etc., and the extraction method from aloe will be described below as an example. .

There is no limitation on the method of extracting aloe,
An ordinary extraction method is adopted, and extraction is performed using water, a hydrophilic organic solvent, a water-containing hydrophilic organic solvent, another organic solvent or the like. The present applicant has made some proposals as an aloe extraction method, and the following method is particularly preferable.

Specifically, the aloe sap is subjected to a first batch of activated carbon treatment by the batch method, then the solution from which the activated carbon has been removed is concentrated, and this concentrated liquid is subjected to the second batch of activated carbon treatment by the batch method. Then, the activated carbon is removed to obtain a solution, and a substance having a physiologically active action is produced from aloe (Japanese Patent Publication No. 5834/1993).

The following is an example of a method for synthesizing the novel ceramide derivative of the present invention, but the present invention is not limited to these methods. The ceramide derivative of the present invention, which has a structure in which ceramide and α-hydroxycarboxylic acid are linked by an ether bond, is a leaving group at the α-position of a carboxylic acid and protection of a carboxyl group, and etherification of the carboxylic acid derivative and ceramide. Then, it can be synthesized through three steps of purification.

First, the steps will be described. It is difficult to directly etherify a carboxylic acid whose α-position is unsubstituted and a ceramide by a general organic synthesis method. Further, even if the α-position of the carboxyl group is a hydroxyl group, most ceramides have only a hydroxyl group as a reactive functional group, and therefore cannot be directly etherified. Therefore, in order to ether bond the α-position of the carboxyl group with the ceramide by organic synthesis, as the first step, a reactive functional group capable of etherification with the hydroxyl group of the ceramide is introduced at the α-position of the carboxylic acid in the step of There is a need. Examples of the leaving functional group suitable for such a purpose include a halogen group such as a chloro group and a bromine group, and a tosyl group. Introducing these functional groups into the α-position of the carboxyl group means that any starting material can be used regardless of whether the α-position is an unsubstituted carboxylic acid as a starting material or an α-hydroxycarboxylic acid as a starting material. However, a known method is possible.

That is, for example, in order to introduce a bromine group into the α-position of a carboxylic acid whose α-position is unsubstituted, Hell-Volhard-Zel
It may be synthesized by a method of reacting with bromine in the presence of a phosphorus catalyst known as the insky method, or a method of reacting with bromine via an acid chloride known as the Schwenk-Papa method (RSSeet, FLEstes, J.Org). .Chem., 21,1426 (195
6))). These reactions can be performed in a solventless system,
It is also possible to use a halogen-based solvent such as carbon tetrachloride or a solvent inert to bromine such as dioxane or dimethyl sulfoxide. The reaction temperature varies depending on the type of carboxylic acid or solvent used and the like, but is generally possible at a relatively low temperature, and may be appropriately set within the range of 0 to 100 ° C.

On the other hand, when an α-hydroxy acid is used as a starting material, α is well known, for example, as a nucleophilic substitution reaction.
-The α-position can be halogenated by a method in which a hydroxy acid is directly reacted with hydrogen halide. This reaction can also be carried out without solvent depending on the system, but in general, a method using a solvent is preferred. Preferred solvents for this reaction include, but are not limited to, halogenated solvents such as carbon tetrachloride and dioxane, dimethylsulfoxide, and other inert solvents to hydrogen halides. The reaction temperature varies depending on the type of α-hydroxycarboxylic acid used and the solvent used, but is 20-80.
It is preferable to set in the range of ° C.

The thus-obtained carboxylic acid derivative having a leaving group at the α-position can be used as it is for etherification, but in some cases, an ester is by-produced during etherification with ceramide. Therefore, if such a by-product is not preferable, the carboxyl group of the carboxylic acid is protected by previously esterifying it with an alcohol such as methanol or silylating it with a silylating agent such as silyl chloride. You should keep it.

Next, the etherification step will be described. Although etherification can be carried out by various methods, a preferred example is a compound having a leaving group such as a bromine group after reacting a hydroxyl group with a base to form an alcoholate, which is well known as Williamson synthesis. And a desalting etherification. This reaction can also be applied to ceramides, in which the hydroxyl group of ceramides is converted to an alcoholate by reacting ceramides with a base, and then the carboxylic acid derivative having a leaving group at the α-position previously synthesized is removed. By salt-etherification, the ceramide derivative of the present invention having a structure in which ceramides and α-hydroxycarboxylic acid are ether-bonded to each other, which is a target product, can be obtained.

Examples of the base used for alcoholating ceramide include alkali metals such as sodium and potassium and hydroxides thereof, and tertiary alcoholates such as potassium tert-butoxide. This alcoholation is preferably carried out in a solvent system, and examples of the solvent include tert-butanol, dioxane and the like, but the solvent is not limited to these, and may be selected in consideration of solubility depending on the type of ceramides. The temperature of this reaction varies depending on the type of base and the type of ceramides, but is 30 to 1
It is preferably carried out at 30 ° C. If it is too low, the reaction does not proceed, and if it is too high, the ceramides are decomposed and many by-products are produced. After completion of alcoholation of ceramide, desalting etherification proceeds rapidly by gradually adding the carboxylic acid derivative having a leaving group introduced at the α-position to the reaction system.

Since the reaction mixture thus obtained often contains by-produced inorganic salts, unreacted substances, and decomposition products of a part of ceramide, the reaction product is purified as a next step. Is preferred. The purification can be performed by a known method such as recrystallization, filtration, or column chromatography, but purification by column chromatography using silica gel is preferable in order to improve the purification purity.

The ceramide derivative of the present invention may be one having a structure in which a ceramide or ceramide analogue and a hydroxycarboxylic acid are ether-bonded, and the ceramide or ceramide analogue and the hydroxycarboxylic acid are in a molar ratio. It may be 1: 1, 1: 2, 1: 3 or more. On the contrary, it may be 2: 1, 3: 1 or more. When a plurality of hydroxycarboxylic acids are ether-bonded to the OH group of ceramide or a ceramide analogue, different types of hydroxycarboxylic acids may be bonded. Furthermore, when the ceramide derivative of the present invention is used, it may be used as a single ceramide derivative compound or as a mixture of a plurality of ceramide derivative compounds each having different ceramide or hydroxycarboxylic acid.

Next, a cosmetic material which is another embodiment of the present invention will be described. The cosmetic according to the present invention contains at least one of the ceramide derivatives as an active ingredient. Here, the cosmetics include various cosmetic creams, emulsions, lotions, beauty essences, packs, undermake-ups, foundations, gels, ointments and other external skin compositions, oral cosmetics, bath cosmetics, hair. It is a composition used for various purposes such as cosmetics.

The cosmetics according to the present invention need to contain at least one of the ceramide derivatives as an active ingredient, and the desired cosmetics may be prepared by adding and mixing various optional ingredients depending on the application. Can be prepared. The amount of the ceramide derivative compounded as an active ingredient in various cosmetic compositions is preferably 0.01 to 20% by weight (hereinafter, simply referred to as%), and particularly preferably 0.1 to 5%.

In the cosmetic of the present invention, in addition to the above-mentioned essential components, materials usually used for cosmetics such as external preparations, for example,
Surfactants, oils, alcohols, moisturizers, thickeners, preservatives, antioxidants, chelating agents, pH adjusters, fragrances, dyes, UV absorbers / scatterers, amino acids, water, etc. may be added. it can.

Specifically, the surfactants include lipophilic glycerin monostearate, self-emulsifying glycerin monostearate, polyglycerin monostearate, sorbitan monooleate, polyethylene glycol monostearate, polyoxyethylene sorbitan. Monooleate, polyoxyethylene cetyl ether, polyoxyethylene sterol, polyoxyethylene lanolin,
Nonionic surfactants such as polyoxyethylene beeswax and polyoxyethylene hydrogenated castor oil; sodium stearate, potassium palmitate, sodium cetyl sulfate,
Anionic surfactants such as sodium lauryl phosphate, triethanolamine palmitate, sodium polyoxyethylene lauryl phosphate, sodium N-acylglutamate; cationic surfactants such as stearyldimethylbenzylammonium chloride and stearyltrimethylammonium chloride, alkyl chlorides Aminoethylglycine solution,
Examples thereof include amphoteric surfactants such as lecithin.

As the oil component, vegetable oils such as castor oil, olive oil, cacao oil, camellia oil, coconut oil, wax, jojoba oil, grape seed oil, avocado oil and the like; animal oils and fats such as mink oil and egg yolk oil; honey Wax such as wax, spermaceti, lanolin, carnauba wax, candelilla wax; hydrocarbons such as liquid paraffin, squalane, microcrystalline wax, ceresin wax, paraffin wax, petrolatum; lauric acid, myristic acid, stearic acid, oleic acid , Natural and synthetic fatty acids such as isostearic acid, behenic acid; cetanol, stearyl alcohol,
Natural and synthetic higher alcohols such as hexyldecanol, octyldodecanol, and lauryl alcohol; esters such as isopropyl myristate, isopropyl palmitate, isopropyl adipate, octyldodecyl myristate, octyldodecyl oleate, cholesterol oleate, etc. You can

As the moisturizer, polyhydric alcohol,
GMF, propylene glycol, 1,3-butylene glycol, sorbitol, polyglycerin, polyethylene glycol, dipropylene glycol, etc.
Examples of (Natural Moisturizing Factor) components include amino acids and sodium pyrrolidonecarboxylate, and examples of water-soluble polymer substances include hyaluronic acid, collagen, elastin, mucopolysaccharide, and chondroitin sulfate.

As the thickener, sodium alginate,
Natural polymer substances such as xanthan gum, aluminum silicate, quince seed extract, tragacanth gum and starch;
Examples thereof include semi-synthetic polymer substances such as methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, soluble starch and cationized cellulose; synthetic polymer substances such as carboxy vinyl polymer and polyvinyl alcohol.

Preservatives include benzoate, sorbate, dehydroacetate, paraoxybenzoate,
2,4,4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorocarbanilide,
Benzalkonium chloride, hinokitiol, resorcin,
Ethanol etc. can be illustrated.

As antioxidants, dibutylhydroxytoluene, butylhydroxyanisole, ascorbic acid, etc .; as chelating agents, disodium edetate,
Ethylenediaminetetraacetic acid salt, pyrophosphate, hexametaphosphate, gluconic acid, etc .; pH adjusting agents such as sodium hydroxide, potassium hydroxide, triethanolamine, aqueous ammonia, boric acid, borax, potassium hydrogen phosphate, etc. Can be illustrated respectively.

Examples of the ultraviolet absorbing / scattering agent include 2-hydroxy-4-methoxybenzophenone, octyldimethylparaaminobenzoate, ethylhexylparamethoxycinnamate, titanium oxide, kaolin, talc and the like.

As the vitamins, vitamin A, vitamin B group, vitamin C, vitamin D, vitamin E, vitamin F, vitamin K, vitamin P, vitamin U, carnitine, ferulic acid, γ-oryzanol, α-lipoic acid, Examples thereof include orotic acid and derivatives thereof.

As amino acids, glycine, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid,
Examples thereof include glutamic acid, arginine, histidine, lysine, asparagine, glutamine and their derivatives.

The optional components are not limited to these. The following cosmetics can be provided by appropriately blending the ceramide derivative which is the above-mentioned essential component and an optional component. In the following description, the ceramide derivative means at least one selected from the group of compounds represented by the general formula (1) or (2).
3 shows a ceramide derivative of a species.

(1) Cream for skin Ceramide derivative 0.1-10%, oil content 3-70%, surfactant 0.5-7%, moisturizer 0-10%, pH adjuster 0
~ 3%, purified water balance, preservative traces, perfume traces composition. (2) Emulsion 0.1 to 10% ceramide derivative, 3 to 40% oil, 0 to 15% alcohol, 0.3 to 5% surfactant, 0 to 10% humectant, 0 to 2% thickener A composition containing 0 to 3% of a pH adjuster, purified water balance, a trace amount of a preservative, and a trace amount of a fragrance. (3) Lotion, beauty liquid Ceramide derivative 0.1-10%, oil content 0-40%, surfactant 0-2%, moisturizer 0-8%, thickener 0-2%, antioxidant 0 ~ 0.5%, chelating agent 0-0.1%, pH
Conditioner 0-3%, purified water balance, preservative trace amount, dye 0
~ A composition containing a trace amount of a fragrance. (4) Packing agent Ceramide derivative 0.1 to 10%, alcohols 2 to 20
%, A moisturizing agent 0 to 10%, a surfactant 0 to 10%, an inorganic powder 0 to 20%, a film forming agent 5 to 20%, a purified water balance, a preservative trace amount, and a perfume trace amount. (5) Gel agent Ceramide derivative 0.1-10%, alcohols 0-10
%, Moisturizer 0-20%, surfactant 0-10%, thickener 0.01-20%, pH adjuster 0-3%, purified water balance, preservative trace amount, perfume trace amount composition .

[0044]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in more detail with reference to embodiments. However, the present invention is not limited to the following examples.

(Preparation of Ceramide Derivative) The ceramide derivative according to the present invention was synthesized as shown in FIG. First,
Directly react lactic acid with 48% hydrobromic acid at a temperature of 50 to 1
The reaction was carried out at 00 ° C, preferably 70 to 90 ° C, and the α-position was brominated. Next, ceramide 2 shown in Table 1 was treated with sodium hydride (N) in a dimethyl sulfoxide (DMSO) solvent.
aH) and room temperature (0 to 40 ° C, preferably 15 to 30 ° C)
Was reacted with and converted into alcoholate. Here, to the reaction system, a carboxylic acid derivative having a leaving group at the α-position, a bromine group, was gradually added at a temperature of 40 to 120 ° C., preferably 50 to 70 ° C. to form an ether bond to obtain the target ceramide derivative 1. .
Purification was performed by column chromatography using silica gel. Similarly, ceramide or ceramide analogue was reacted with hydroxycarboxylic acid to prepare ceramide derivatives 2-4. Table 2 shows the structures of the prepared ceramide derivatives 1 to 4.

[0046]

[Table 2]

(Example 1) The ceramide derivatives 1 to 4 according to the present invention shown in Table 2 were blended to prepare a cream having the composition shown in Table 3. As a comparative example, various kinds of hydroxycarboxylic acids were blended in place of the ceramide derivative to prepare a cream in the same manner. Table 4 shows the types and blending amounts of the ceramide derivative (invention products 1 to 4) and the hydroxycarboxylic acid (comparative examples 1 to 8).

[0048]

[Table 3]

[0049]

[Table 4]

The above components 1 to 8 and the components 9 to 14 were separately heated and dissolved at 70 ° C., mixed and emulsified, and the component 15 was added during cooling to cool to room temperature.
And the creams of Comparative Examples 1 to 8 were prepared.

The effectiveness of the cream thus prepared was evaluated as follows. That is, men 20 to 55 years old
The name was selected, the prepared cream was applied to the outer corners of the eyes, and the presence or absence of irritation was evaluated. The results are shown in Table 5.

[0052]

[Table 5]

From the results shown in Table 5, the products 1 to 4 of the present invention containing the ceramide derivatives 1 to 4 can reduce the irritation sensation peculiar to the hydroxycarboxylic acid, as compared with the comparative examples 1 to 8 containing the hydroxycarboxylic acid. did it.

Using the above cream, the effect of improving fine wrinkles among the effects of hydroxycarboxylic acid was evaluated. 3
Ten males of 0 to 40 years old were selected for each sample and applied to the outer corners of the eyes twice a day for three consecutive months, and the degree of improvement of fine wrinkles was evaluated. Criteria for visual fine wrinkles 1 No improvement 2 Some improvement 3 Some improvement 4 Almost improvement 5 Improvement results are shown in Table 6 (score is average of n = 10).

[0055]

[Table 6]

From the above results, it can be seen that the ceramide derivatives 1 to 4 according to the present invention are highly effective in improving fine wrinkles as much as or better than hydroxycarboxylic acid. That is, it was revealed that the ceramide derivatives 1 to 4 according to the present invention reduce the irritation sensation peculiar to hydroxycarboxylic acid, and have a fine wrinkle improving effect equal to or higher than that of hydroxycarboxylic acid.

Example 2 A cream (product of the present invention) 5 containing the ceramide derivative of the present invention was prepared by the following method, and its moisturizing effect was examined. Ingredients 1 to 1 listed in Table 7
9 and components 10 to 16 were separately heated and dissolved at 70 ° C.,
The mixture was emulsified, and component 17 was added during cooling and cooled to room temperature to prepare a cream. The blending amount is represented by% by weight.

[0058]

[Table 7]

Moisturizing ability improvement test using skin surface stratum corneum water content measuring device Acetone was applied to the inside of the forearm of 20 males aged 30 to 40:
Degreasing was performed with a mixed solvent of ether = 1: 1 to prepare rough skin. The prepared cream was applied twice a day, and after 3 days, conductance was measured by a skin surface stratum corneum water content measuring device (SKICON-200 manufactured by IBS). The results are shown in Table 8

[0060]

[Table 8]

From the results shown in Table 8, it was revealed that the ceramide derivative according to the present invention exhibits higher moisturizing power than the case where hydroxycarboxylic acid or ceramide is used alone.

Example 3 A cream containing the ceramide derivative according to the present invention (Product 6 of the present invention) was prepared by the following method, and its moisturizing effect was examined. Components 1 shown in Table 9
9 and components 10 to 16 were separately heated and dissolved at 70 ° C.,
The mixture was emulsified, and component 17 was added during cooling and cooled to room temperature to prepare a cream. The blending amount is represented by% by weight.

[0063]

[Table 9]

Visual Test for Rough Skin Improvement Evaluation Twenty males aged 25 to 55 were degreased with a mixed solvent of acetone: ether = 1: 1 on the inner forearm to prepare rough skin. The prepared cream was applied twice a day, and after 3 days, the degree of improvement of rough skin was evaluated visually. Visual Evaluation Criteria The condition of rough skin was evaluated as follows. 1 No improvement 2 Some improvement 3 Some improvement 4 Almost improvement 5 Improvement evaluation results are shown in Table 10. The evaluation score is the average of n = 20.

[0065]

[Table 10]

From the results shown in Table 10, the product of the present invention has a significantly higher effect of improving rough skin than the comparative example. That is, it was revealed that the ceramide derivative according to the present invention dramatically improves the rough skin improving effect as compared with the case where hydroxycarboxylic acid or ceramide is used alone.

Example 4 A cream containing the ceramide derivative according to the present invention (Product 7 of the present invention) was prepared by the following method, and its moisturizing effect was examined. Ingredient 1 listed in Table 11
~ 7 and components 8-16 were separately heated and dissolved at 70 ° C,
The mixture was emulsified, and component 17 was added during cooling and cooled to room temperature to prepare a cream. The blending amount is represented by% by weight.

[0068]

[Table 11]

The effectiveness of the cream prepared above was evaluated as follows. Twenty women aged 35 to 55 were selected twice a day (morning and night) for 3 consecutive months, product 8 of the present invention
After using and and Comparative Example 13 separately on the left and right faces by the half-face method, the absence of irritation and the degree of improvement of fine wrinkles due to the effect of hydroxycarboxylic acid were examined. Table 12 shows the results.

[0070]

[Table 12]

From the results shown in Table 12, the product of the present invention showed less irritation as compared with the comparative example, and showed the same improvement effect on fine wrinkles.

Example 5 An emulsion (invention product 8) containing the ceramide derivative according to the present invention was prepared by the following method. Components 1 to 5 shown in Table 13 were heated and dissolved at 70 ° C. On the other hand, components 6 to 10 are heated and dissolved at 70 ° C., the above-mentioned oil and fat solutions (components 1 to 5) are added to emulsify, and then component 11 is added during cooling and cooled to room temperature to prepare an emulsion. did. The blending amount is represented by% by weight.

[0073]

[Table 13]

Twenty women aged 35 to 55 were selected, and the prepared emulsion was twice a day (morning and night) for 3 consecutive months and half
After the face method was used separately for the right and left faces, the absence of irritation and the degree of improvement of fine wrinkles due to the effect of hydroxycarboxylic acid were examined. The results are shown in Table 14.

[0075]

[Table 14]

From the results shown in Table 14, the product of the present invention showed less irritation as compared with the comparative example, and showed an equivalent improvement effect on fine wrinkles.

[0077]

As described above, the ceramide derivative of the present invention was able to reduce the peculiar stimulating feeling without deteriorating the effect of hydroxycarboxylic acid. In addition, it was also found that it is more effective than hydroxycarboxylic acid and ceramide in improving skin roughness and moisturizing ability. By blending the ceramide derivative of the present invention, it is possible to provide a composition for external use for skin such as a drug, a quasi drug, and a cosmetic product, which has excellent effects by the ceramide derivative and is highly safe. Further, since the cosmetic of the present invention contains at least one of the ceramide derivatives as an active ingredient, it has various effects of the ceramide derivative and is highly safe, and various cosmetic creams, emulsions and cosmetics. It can be widely used in various forms such as water, beauty essence, pack, undermake-up, foundation, gel and ointment.

[Brief description of drawings]

FIG. 1 is a diagram for explaining a method for synthesizing a ceramide derivative produced in an example of the present invention.

Claims (2)

[Claims] 1. A compound of the general formula (1) Or general formula (2) [However, R1 straight chain having 8 to 30 carbon atoms, branched, aliphatic hydrocarbon group not Yusuke or have a hydroxyl group, saturated or unsaturated or _{Y-O- (C d H e} ), - a is , Y is represented by the formula (3): (Where Z is a hydroxyl group or epoxy oxygen, d
Is an integer of 8 to 50, e is an integer of 10 to 100, and f is 12
~ 20 integer, g is 20-40 integer, h is 0 or 1
R2 is an aliphatic hydrocarbon group having or not having a linear, branched, saturated or unsaturated hydroxyl group having 8 to 30 carbon atoms; A
Is _{-CH 2 -, - CH 2 O} -, - CH = CH -, - CH
(O · HS)-or the formula (4): HS is the formula (5), the formula (6) [Chemical 6] (Here, X is hydrogen or an aliphatic hydrocarbon group having or not having a linear, branched, saturated or unsaturated hydroxyl group having 1 to 30 carbon atoms, a is an integer of 0 to 9, and b is 1 ~
At least one α-hydroxy acid residue selected from the group consisting of 9), or one of them is H—; i is 1 or 2.]. 2. A cosmetic comprising at least one of the ceramide derivatives according to claim 1 as an active ingredient.