JP2002332208A - Composition of preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition of a preparation for external use, a humec tant and a skin barrier function reinforcing agent capable of essentially improv ing a water holding ability and barrier functions of horny layers, having excel lent formulating properties and formulation stability and efficiently producible at low cost. SOLUTION: The composition for the external use, humectant and skin barrier function reinforcing agent comprise a diamide derivative represented by the following general formula (1) (wherein, R<1a> and R<1b> are each the same or different and denote each a 1-23C hydrocarbon group; R<2a> and R<2b> are each the same or different and denote each a 1-6C bivalent hydrocarbon group; R<3> s are each the same or different and denote each a 2-6C bivalent hydrocarbon group; and n denotes a number of 1-100).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a compound exhibiting an effect of improving skin roughness by maintaining a normal barrier function of the stratum corneum of the skin and improving the water retention ability, and an external preparation composition containing the compound.

[0002]

2. Description of the Related Art When the water holding capacity and barrier function of the stratum corneum are reduced by various internal or external causes, various skin troubles such as roughening of the skin and aging are promoted. Wake up. In addition, in the rough skin symptoms observed in various skin diseases such as atopic dermatitis, psoriasis, and xeroderma, a decrease in the water retention ability and barrier function of the stratum corneum has been observed. Therefore, maintenance and reinforcement of the water retention ability and barrier function of the stratum corneum are very important for healthy daily living.

Under such circumstances, the present applicant has applied an amide derivative represented by the following general formula (2) as a skin external preparation having an effect of essentially improving (maintaining and reinforcing) the barrier function of the stratum corneum. A patent application was filed for the contained external preparation for skin and the like (Japanese Patent Laid-Open No. 4-128256).

[0004]

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(Wherein, R ^a represents a straight-chain or branched-chain saturated or unsaturated hydrocarbon group having 10 to 40 carbon atoms, and R ^b represents a straight-chain or branched divalent hydrocarbon group having 3 to 39 carbon atoms.) And R ^c represents a hydrogen atom, a linear or branched saturated or unsaturated hydrocarbon group having 10 to 40 carbon atoms or an acyl group.)

[0006] However, such amide derivatives provide the above-mentioned excellent effects, but they do not always have sufficient solubility and stability with respect to the base. There was room for improvement in terms of gender. In addition, the production of these amide derivatives requires a multi-step reaction, which inevitably increases the production cost.

An object of the present invention is to provide a composition for external use which substantially improves the water retention ability and barrier function of the stratum corneum, has excellent blending properties and blending stability, and can be manufactured efficiently and at low cost. Aim.

[0008]

Means for Solving the Problems The present inventors further studied amide derivatives, and found that the diamide derivative represented by the following formula (1) has an action of enhancing the water retention ability of the stratum corneum and an action of improving the barrier function. It also has excellent compoundability and compounding stability, and has been found to be useful as an external preparation composition having an effect of preventing and improving skin troubles such as rough skin and an effect of protecting hair.

That is, the present invention provides the following general formula (1):

[0010]

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(Wherein, R ^1a and R ^1b are the same or different and represent a hydrocarbon group having 1 to 23 carbon atoms, and R ^2a and R ^2b are the same or different and are a divalent hydrocarbon having 1 to 6 carbon atoms.) R ³ represents the same or different and represents a divalent hydrocarbon group having 2 to 6 carbon atoms, and n represents a number of 1 to 100.)

An external preparation composition containing the diamide derivative represented by the formula (1), an external preparation composition containing the diamide derivative and a keratinocyte intercellular lipid component, a humectant containing the diamide derivative as an active ingredient, and a skin barrier function enhancer Is provided.

Further, the present invention provides the following general formula (1 ′):

[0014]

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(Wherein R ^{1a ′} and R ^{1b ′} are the same or different and represent a branched chain hydrocarbon group having 4 to 23 carbon atoms, and R ^2a and R ^2b are the same or different and have 1 to 6 carbon atoms. Represents a divalent hydrocarbon group, R ³ is the same or different and represents a divalent hydrocarbon group having 2 to 6 carbon atoms, and n represents a number of 1 to 100.)

The present invention provides a diamide derivative represented by the formula:

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION In the diamide derivative (1) of the present invention, the hydrocarbon group having 1 to 23 carbon atoms represented by R ^1a and R ^1b is a linear or branched alkyl group having 5 to 17 carbon atoms. Or an alkenyl group, and more preferably R ^1a and R
^It is preferred that ^1b be the same. Particularly preferred hydrocarbon groups include pentyl, heptyl, nonyl, undecyl,
Examples include tridecyl, pentadecyl, heptadecyl, 1-ethylheptyl, 2,4,4-trimethylpentyl, 1-heptyldecyl, isoheptadecyl, methyl-branched isoheptadecyl, 8-heptadecenyl, and 8,11-heptadecadienyl groups.

The compound represented by the general formula (1 ') wherein R ^1a and R ^1b are each a branched hydrocarbon group having 4 or more carbon atoms is a novel compound.

Examples of the divalent hydrocarbon group having 1 to 6 carbon atoms represented by R ^2a and R ^2b, preferably an alkylene group having a straight-chain or branched-chain having 2 to 6 carbon atoms, still more R ^2a and R ^2b Preferably, they are the same. Particularly preferred divalent hydrocarbon groups include ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, 1-methylethylene,
Examples thereof include a 2-methylethylene group, and among them, a 1-methylethylene and a 2-methylethylene group are more preferable.

As the divalent hydrocarbon group having 2 to 6 carbon atoms represented by R ³ , a linear or branched alkylene group having 2 to 6 carbon atoms is preferable.
Tetramethylene, pentamethylene, hexamethylene, 1
-Methylethylene, 2-methylethylene group, 2,2-dimethyltrimethylene and the like are preferable, and particularly, ethylene, 1-
Methylethylene and 2-methylethylene groups are preferred.

Further, n is preferably a number of 1 to 50, more preferably a number of 1 to 10, and particularly preferably a number of less than 4.

Preferred diamide derivatives (1) include:
R ^1a , R ^1b , R ^2a , R ^2b , R ³ and n in the general formula (1)
Preferred are compounds in which the groups shown above are combined, and among them, compounds in which some or all of the hydrocarbon groups of R ^1a , R ^1b , R ^2a , R ^2b and R ³ have a branched chain are Since it has a low melting point and excellent compoundability, it is more preferable than a compound composed entirely of linear hydrocarbons. The diamide derivative (1) used in the external preparation composition of the present invention can be produced by a known amide synthesis method. For example, according to the following production method, it can be produced efficiently and at low cost.

[0023]

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(Wherein, R ^1a , R ^1b , R ^2a , R ^2b , R ³ and n have the same meaning as described above.)

That is, by reacting the corresponding diamine (3) with a carboxylic acid (4a) and / or (4b) or a reactive derivative thereof (ester, acid halide, acid anhydride, etc.), the desired diamide derivative ( 1) can be obtained efficiently.

The conditions of this reaction include a dehydrating agent such as dicyclohexylcarbodiimide or an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, or an alkali metal such as potassium carbonate. In the presence or absence of a base such as an alkali earth metal carbonate such as metal carbonate and calcium carbonate, an alkali metal alcoholate such as sodium methoxide, sodium ethoxide and potassium tert-butoxide, and a tertiary amine such as triethylamine and pyridine. In the presence, normal pressure to 1.3
The reaction is preferably performed at room temperature to 300 ° C. under a reduced pressure of Pa. At this time, the carboxylic acid (4a) and / or (4b) or its reactive derivative is preferably used in excess relative to the diamine (3), that is, at least 2 equivalents, and water or alcohol generated by the reaction is removed out of the system. It is preferable to perform the reaction while the reaction proceeds rapidly. The diamide derivative (1) thus obtained is washed with water, liquid-liquid distribution,
Purification can also be performed by a known method such as column chromatography, distillation, crystallization, recrystallization or powder treatment.

Examples of the diamine (3) include polyoxyethylene diamine, polyoxypropylene diamine, and polyoxyethylene-oxypropylene diamine. Specific examples thereof include Jeffamine (“JEFFINE”).
AMINE ”(registered trademark), HUNTSMAN CORPOR
ATION)) Polyoxyalkylenediamines.

The diamide derivative (1) of the present invention thus obtained has the effect of maintaining and improving the barrier function of the stratum corneum of the skin and improving the moisture retention ability of the stratum corneum, as will be described in Examples below. It is useful as an agent and a skin barrier function enhancer, and an external preparation composition containing the same is effective for improving rough skin and the like.

In the present invention, when a water-soluble humectant selected from a polyhydric alcohol, an organic acid or a salt thereof or a derivative thereof, and a plant extract is combined, the water holding capacity of the stratum corneum can be synergistically increased. . Examples of polyhydric alcohols include polyglycerin such as glycerin, diglycerin, triglycerin, and tetraglycerin, ethylene glycol, 1,3-butylene glycol, 1,4-
Butylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol, 1,3-propanediol, glucose, maltose, maltitol, sucrose, fructose, xylitol, sorbitol, maltotriose, threitol, erythritol, amylolytic alcohol, sorbitol And polyoxyalkylene alkyl glucosides. Of these, glycerin, 1,3-butylene glycol, propylene glycol and dipropylene glycol are particularly preferred.

Two or more polyhydric alcohols may be used in combination. The content in the external preparation composition of the present invention is 0.1.
When the content is 001 to 50% by weight (hereinafter simply referred to as%), preferably 0.01 to 40%, and particularly preferably 0.1 to 30%, the water retention capacity of the stratum corneum can be synergistically increased. is there.

Examples of the organic acids and organic acid derivatives include oxycarboxylic acids having 2 to 28 carbon atoms such as glycolic acid, lactic acid, citric acid and 2-hydroxyoctanoic acid; succinic acid, fumaric acid, maleic acid, malonic acid, C2-C12 dicarboxylic acids such as 2,3-propanedicarboxylic acid; amino acids such as aspartic acid, asparagine, glycine, glutamic acid, glutamine, γ-aminobutyric acid, arginine, cysteine, and alanine and derivatives thereof; octyl succinate;
Dicarboxylic acid monoesters such as methyl maleate; nicotinic acid, methyl nicotinate, ethyl nicotinate, benzyl nicotinate, nicotinamide, tocopherol nicotinate, quinolinic acid, pyridine-3,5-dicarboxylic acid, nicotinamide adenine di Nicotinic acid such as nucleotide phosphate (NADP), nicotinic acid mononucleotide, nicotinyl alcohol, nicotinyl tartrate or a salt thereof, or a derivative thereof, and a general formula (5)

[0032]

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The sterine derivative represented by

As the above sterine derivatives, those having 1 to 2 in the general formula (5) are preferred, R ⁶ is preferably hexadecenyl or octadecenyl, and R ⁵ is preferably cholesteryl or sitosteryl.

Such organic acids and organic acid derivatives include α
-Hydroxycarboxylic acids, amino acids, nicotinic acid and derivatives thereof are preferable, and glycolic acid, lactic acid, citric acid, succinic acid, aspartic acid, glycine, arginine, nicotinamide, tocopherol nicotinate, and glycine betaine are particularly preferable.

The salts of organic acids include, for example, lactic acid,
Examples include potassium, sodium, magnesium, calcium, aluminum, and basic amino acid salts such as citric acid and succinic acid.When the organic acid has a basic group, for example, acid addition such as hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid Salts.

The organic acid or its salt or its derivative is 2
More than one species may be used in combination. The content in the external preparation composition of the present invention is 0.0001 to 10%, particularly 0.001 to 10%.
It is preferable to contain 〜5%.

As the plant extract, for example, Japanese Patent Application Laid-Open No. 9-1
65313 gazette. Among these, in particular, eucalyptus, hops, ginger, fennel, ganpiruoki, neubara, eucalypt, lily, adlay barley, gama, loquat, gardenia, panax ginseng, savonsou, birch, amacha, clove, safflower, waremokou, iris and clara Extract,
Steam distillates or pressed products are preferred. Examples of the extraction solvent include water, ethanol, 1,3-butylene glycol and the like. Two or more plant extracts may be used in combination. The content in the external preparation composition of the present invention is 0.0001 to 10%, particularly 0.001 in terms of a dry solid component.
It is preferably contained in an amount of from 0.01 to 5%.

In the present invention, the keratin intercellular lipid component selected from ceramides, pseudoceramide, glycosphingolipid, sphingolipid, sphingosine and its derivatives, sphinganine and its derivatives, higher fatty acids, cholesterol and its derivatives, etc. By combining them, it is possible to synergistically increase the barrier function of the stratum corneum.

The ceramides include natural ceramides extracted and purified from brain and skin and synthetic ceramides synthesized by microbiological or chemical methods. Examples of the natural ceramide include ceramides of type I to type VII, N-oleoyl sphingosine, N- (12-hydroxyoctadecanoyl) sphingosine, N- (16-hydroxyhexadecanoyl) sphingosine, bovine brain ceramide and the like. . As a method for synthesizing a synthetic ceramide, for example, JP-A-59-7118, JP-A-4-342553
And the methods described in WO 93/22281 can be used.

On the other hand, pseudoceramide is disclosed in, for example, JP-A-62-228048 and JP-A-63-216852.
It can be manufactured according to the method described in Japanese Patent Publication No. Particularly preferred pseudoceramides include compounds represented by the following formula (6).

[0042]

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(Wherein, R ⁷ represents an alkyl group having 9 to 17 carbon atoms, and R ⁸ represents an alkyl group having 10 to 18 carbon atoms)

As the glycosphingolipids and phosphosphingolipids, there are natural and synthetic sphingolipids similar to the above-mentioned ceramides. Glycosphingolipids include, for example, those whose constituent sugars are composed of glucose, mannose, galactose, glucuronic acid, glucosamine and the like, and also include cerebroside and its sulfate. The sphingomyelin is exemplified by sphingomyelin.

Sphingosines preferably used in combination with ceramides, pseudoceramides, glycosphingolipids and sphingolipids include sphingosines disclosed in JP-A-5-85924 and JP-A-6-27.
Compounds represented by the general formula (7) disclosed in JP-A-1446 and compounds represented by the general formula (8) disclosed in JP-A-5-194185 are preferred.

Sphingosines disclosed in JP-A-5-85924 include sphingosine (sphingenin), dihydrosphingosine (sphinganine),
Phytosphingosine, dehydrosphingosine, dehydrophytosphingosine, sphingdienin, and their N-methyl or N, N-dimethyl forms. The carbon number of the hydrocarbon group of these compounds is 12 to 2
4 is preferred, and it may be either linear or branched saturated or unsaturated.

Compound (7) disclosed in JP-A-6-271446 is

[0048]

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Compound (8) disclosed in JP-A-5-194185 is

[0050]

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(Wherein R ¹⁰ represents a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 4 to 40 carbon atoms, and R ¹¹ , R ¹² , R ¹³ , R ¹⁴ and R ¹⁵ Each represents a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms which may be substituted by one or more hydroxyl groups).

As the higher fatty acid, those having 12 or more carbon atoms, particularly those having 12 to 24 carbon atoms are preferable, and myristic acid,
Palmitic acid, palmito oleic acid, stearic acid, oleic acid, linoleic acid, behenic acid and the like. Monoglycerides, diglycerides, and triglycerides rich in these higher fatty acids may be blended.

As the cholesterol ester, those composed of higher fatty acids having 12 or more carbon atoms, especially 12 to 24 carbon atoms are preferable. Cholesterol palmitate, cholesterol isostearate, N-lauroyl-L-glutamic acid di (cholesterol, 2-octyldodecyl) are preferable. ), Lanolin fatty acid cholesterol, macadamian nut oil fatty acid cholesterol and the like.

Two or more keratin intercellular lipid components may be used in combination. The content in the external preparation composition of the present invention,
0.001 to 20%, particularly preferably 0.005 to 10%.

The content of the diamide derivative (1) in the external preparation composition of the present invention is usually preferably 0.001 to 50% of the total composition in the case of emulsified skin external preparations. In the case of an oily skin external preparation based on hydrogen, the content is preferably 0.01 to 50% of the total composition, and in each case particularly preferably 0.01 to 20%. In particular, the content is preferably 0.1 to 20% for prevention and improvement of rough skin.

The external preparation composition of the present invention is roughly classified into a medicated skin external preparation and a cosmetic in its use form, and is preferably used as a cosmetic, particularly a skin cosmetic. Examples of the medicated skin external preparation include various ointments containing a pharmaceutically active ingredient. The ointment may be any of those based on an oily base and those based on an oil-in-water or water-in-oil emulsion base. Examples of the oleaginous base include vegetable oil, animal oil, synthetic oil, fatty acid, and natural or synthetic glyceride. As the medicinal component, for example, an analgesic anti-inflammatory, an antipruritic, a disinfectant, an astringent, an emollient, a hormone, and the like can be used as necessary.

When used as cosmetics (including skin cosmetics and hair cosmetics), in addition to the diamide derivative (1), which is an essential component, oils, surfactants, and the like generally used as cosmetic components Moisturizers, ultraviolet absorbers, whitening agents, wrinkle improvers, alcohols, chelating agents, pH adjusters, preservatives, thickeners, pigments, fragrances, etc. can be included in any combination.

The cosmetics include various forms such as water-in-oil or oil-in-water emulsified cosmetics, creams, cosmetic emulsions,
Examples include lotions, oily cosmetics, lipsticks, foundations, baths, skin cleansers, nail care, hair cosmetics and the like. Examples of the hair cosmetics include a hair tonic, a hairdressing agent, a hair rinse, a hair treatment, a hair conditioner, a hair styling agent, a shampoo, a hair restorer, and a hair restorer.

In the external preparation composition of the present invention, the medicated skin external preparations and skin cosmetics include surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants and amphoteric surfactants. It can be contained. Of these, nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, fatty acid monoglyceride, and glyceryl ether are preferred. The content is 0.01 to 20 in the composition.
%, Particularly preferably 0.1 to 10%.

When used as a hair cosmetic, the content of the diamide derivative (1) is, for example, 0.001 to 5% for shampoo and the like,
0.1 for conditioners, styling agents, etc.
-20%, and about 0.01-5% for hair liquid, hair tonic, etc.

The hair cosmetic may contain surfactants such as anionic surfactants, cationic surfactants, nonionic surfactants and amphoteric surfactants, and other components generally used in hair cosmetics. it can. When the hair cosmetic is a shampoo, an anionic surfactant such as an alkyl ether sulfate, an alkyl sulfate, or an olefin sulfonate can be contained as a main activator. The content is preferably 5 to 30%, particularly preferably 10 to 20% in the composition.

When the cosmetic of the present invention is a hair rinse, conditioner, hair treatment or hair styling agent, a cationic surfactant such as a mono- or di-long-chain alkyl quaternary ammonium salt is used to impart a good feel to hair. , A nonionic surfactant such as polyoxyethylene alkyl or alkenyl ether, and fats and oils such as liquid paraffin. The content of the cationic and nonionic surfactant is preferably 0.1 to 50%, particularly preferably 0.5 to 20% in the composition.

Further, when the hair cosmetic is a hair liquid, a hair tonic or the like, a nonionic surfactant such as polyoxyethylene can be contained. The nonionic surfactant accounts for 0.01 to 20%, in particular 0.1%, of the total composition.
It is preferable that the content be contained in an amount of about 5%.

[0064]

EXAMPLES Production Example 1 Production of Compound (A)

[0065]

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In a flask equipped with a stirrer, a nitrogen inlet tube and a distillation apparatus, caprylic acid (Lunac 8-98 manufactured by Kao) was added.
(E)) 317 g were charged, and the mixture was stirred under a nitrogen stream and stirred at 220
Jeffamine D-230 (manufactured by Huntsman) 22
8 g was added dropwise over 2.5 hours. Aged for 5 hours under the same conditions. The above dripping and ripening were performed under a nitrogen stream while distilling off by-produced water. After completion of the reaction, molecular distillation (160 to 210 ° C., 0.5 Pa) was performed to obtain 262 g of the title compound (A). Physical properties of compound (A) obtained are as described below.

Colorless oil ¹ H-NMR (CDCl ₃ , δ); 0.80-1.00 (m), 1.00-1.50 (m), 1.50
-1.80 (m), 2.13 (t, J = 7.5Hz), 3.00-3.75 (m), 4.00-4.30
(m), 5.60-6.10 (m).

Production Examples 2 to 11 The following compounds (B) to (k) were prepared in the same manner as in Production Example 1 except that the compounds shown in Table 1 were used as the diamine (3) and the carboxylic acid (4a) or (4b). Was manufactured. Tables 1 and 2 also show the physical properties of each diamide derivative.

[0069]

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[0070]

[Table 1]

[0071]

[Table 2]

Test Example 1 An external preparation composition of the present invention (product of the present invention) having the composition shown in Tables 3 to 5 containing each of the diamide derivatives prepared in Production Examples 1 to 11 was prepared, and these external preparations were prepared. The percutaneous moisture evaporation and transdermal absorption were measured and evaluated by the following methods.
The results are shown in Table 6 below.

(Test Method) Male Wistar rats were bred only with a diet containing no essential fatty acid, and rats having symptoms of essential fatty acid deficiency were used in this test.
After carefully shaving the backs of these essential fatty acid deficiency rats, the external preparation composition was applied once a day for 12 days. In addition,
For each external preparation for evaluation, 5 animals per group were subjected to this test. Three days after completion of the application, the following items were measured and evaluated.

(1) Transdermal Moisture Transpiration The transdermal water loss on the back of the test rat was measured with a tevameter. According to the following formula, the transdermal water evaporation suppression effect was determined. Degree of inhibition of transdermal water evaporation of the product of the present invention = transdermal water evaporation of rat to which comparative product 1 was applied-transdermal water evaporation of rat to which the present product was applied (g / m ² / hr)

(2) Percutaneous absorption The skin on the back of the test rat was cut off, and a percutaneous absorption chamber was used.
Was fixed with the epidermis side up. Phosphate buffer in lower receiver
Fill with saline solution, 37KBq on top of epidermis ¹⁴C-sa
A phosphate buffered saline solution containing lylic acid was added and allowed to stand. 1
Nine hours later, a certain amount of phosphate buffered saline was poured from the lower receiver.
Sampled and infiltrated¹⁴The radioactivity of C-salicylic acid was measured.
Specified. The transdermal absorption inhibitory effect was determined according to the following formula. Percutaneous absorption inhibition of the product of the present invention = transdermal of rat applied with comparative product 1
Absorbance-Percutaneous absorption (dpm) of rats coated with the present invention

[0076]

[Table 3]

[0077]

[Table 4]

[0078]

[Table 5]

[0079]

[Table 6]

The products 1 to 11 of the present invention had a superior effect of suppressing transdermal water evaporation and transdermal absorption as compared with the comparative product 1, and were excellent in the effect of improving skin roughness.

Test Example 2 External preparation compositions of the present invention (products of the present invention) containing the diamide derivative and having the compositions shown in Tables 7 and 8 were prepared, and the percutaneous moisture evaporation of these external preparations was carried out by the following method. And skin conductance were measured and evaluated. In addition, as a comparison, the same measurement and evaluation were performed on an external preparation composition containing Vaseline (Comparative Product 2), which is known to have high skin obstructiveness and is used in a medicated skin external preparation and skin cosmetics. . Table 9 shows the results.

(Test Method) After washing the inner forearm (both arms) of 10 healthy persons, lipids between stratum corneum cells were removed by acetone / ether (1/1) treatment to make the skin rough. The external preparation composition was applied to the test site twice a day for 3 days. The next day, the same site was washed and rested at room temperature of 20 ° C. and humidity of 30% for 20 minutes, and then the following items were measured and evaluated.

(1) Transepidermal water loss The transdermal water loss was measured with a tevameter. According to the following formula, the transdermal water evaporation suppression effect was determined. Degree of suppression of transepidermal water loss of the product of the present invention = transepidermal water loss of base-applied part-transdermal water loss of transdermal water of coated part of the present invention (g / m ² / hr)

(2) Moisture in the stratum corneum The water content in the stratum corneum was measured with a skin conductance meter. The higher the conductance, the higher the water content of the stratum corneum. According to the following formula, the effect of improving the water retention ability of the stratum corneum was determined. Degree of improvement in water retention ability of the product of the present invention = conductance of application part of the present invention−conductance of base application part (μS)

[0085]

[Table 7]

[0086]

[Table 8]

[0087]

[Table 9]

The products 12 to 17 of the present invention were superior to the comparative product 2 in the effect of increasing the water content of the stratum corneum, the effect of suppressing transdermal water evaporation, and the effect of improving skin roughness.

Test Example 3 External preparation compositions of the present invention (products of the present invention) having the compositions shown in Tables 10 and 12 were prepared, and the percutaneous moisture evaporation, skin conductance and skin roughness of these external preparations were evaluated. did. For comparison, the same evaluation was performed for an external preparation composition containing petrolatum (Comparative product 2).
The results are shown in Tables 11 and 13. (Test method) (1) Percutaneous moisture evaporation Evaluated in the same manner as in Test Example 2. (2) Moisture of stratum corneum Evaluation was made in the same manner as in Test Example 2. (3) Rough skin score Rough skin was observed with the naked eye and judged according to the following criteria. The score was shown as an average value. 0: No rough skin is recognized 1: Slight rough skin is recognized 2: Skin rough is recognized 3: Severe rough skin is recognized

[0090]

[Table 10]

[0091]

[Table 11]

The products 13 and 18 to 26 according to the present invention correspond to the comparative product 2
As compared with the above, the effect of suppressing transdermal water evaporation of the stratum corneum and the effect of improving skin roughness were excellent.

[0093]

[Table 12]

[0094]

[Table 13]

The present inventions 13 and 27 to 33 were superior to the comparative product 2 in the effect of increasing the water content of the stratum corneum and the effect of improving the rough skin.

Test Example 4 A hair rinse (product of the present invention) of the present invention having a composition shown in Tables 14 and 15 containing a diamide derivative was prepared.
The roughness and feel of the hair after treatment with these hair rinses were evaluated by five panelists according to the following criteria. The results are shown in Tables 16 and 17.

-2: Bad -1: Somewhat bad 0: Neither can be said +1: Somewhat good +2: Good

[0098]

[Table 14]

[0099]

[Table 15]

[0100]

[Table 16]

[0101]

[Table 17]

The products 34 to 38 of the present invention were superior to the comparative product 3 in the effect of improving the roughness of the hair and the effect of improving the feel of the hair.

Example 1 A skin lotion was prepared according to a conventional method using the formulations shown in Table 18. The resulting skin lotion has excellent skin roughness prevention
The improvement effect was shown. Compounds (A), (C),
(D), (E), (G) and (K) were excellent in mixability and mix stability.

[0104]

[Table 18]

Example 2 An O / W cream having the composition shown in Table 19 was produced according to a conventional method. The obtained O / W cream exhibited excellent skin roughness prevention / improvement effects. Compounds (A), (C), (D),
(E), (G) and (K) were excellent in compoundability and compounding stability.

[0106]

[Table 19]

Example 3 A shampoo having the composition shown in Table 20 was produced according to a conventional method.
This shampoo improved the feel of the hair and prevented and improved the roughness of the scalp. Compounds (A), (C), (D),
(E), (G) and (K) were excellent in compoundability and compounding stability.

[0108]

[Table 20]

Example 4 A hair liquid composition having the composition shown in Table 21 was produced according to a conventional method. The resulting hair liquid composition imparted excellent style retention and formability and good feel to the hair. Compounds (A), (C), (D), (E), (G), (K)
Was excellent in compoundability and compounding stability.

[0110]

[Table 21]

Example 5 A night cream having the following composition was prepared. The obtained night cream had the effect of recovering and reinforcing the decrease of the barrier function of the stratum corneum of the skin, and further increased the water retention capacity of the stratum corneum, and exhibited the effects of preventing and improving rough skin. Compounds (A), (C), (D), (E), (G) and (K) were excellent in compoundability and compounding stability.

[0112]

[Table 22]

Example 6 A sunscreen emulsion having the following composition was prepared. The obtained sunscreen emulsion had the effect of recovering and reinforcing the decrease in the barrier function of the stratum corneum, and further increased the water retention capacity of the stratum corneum, and exhibited the effects of preventing and improving rough skin. Compounds (A), (C), (D), (E), (G) and (K) were excellent in compoundability and compounding stability.

[0114]

[Table 23]

[0115]

Industrial Applicability The diamide derivative (1) of the present invention permeates the lipid layer between keratinocytes to improve (maintain and reinforce) the water retention ability and barrier function of the horny layer, and penetrates the hair to protect it. It has the effect of enhancing the effect and has good solubility in the base and excellent stability. Therefore, the external preparation composition, moisturizer and skin barrier function enhancer of the present invention prevent and treat rough skin, prevent skin aging, improve the feel of hair,
It exerts effects such as prevention and improvement of rough scalp and is useful as highly stable drugs, cosmetics and quasi-drugs. Furthermore, the external preparation composition of the present invention can be produced efficiently and at low cost.

Continued on the front page (51) Int.Cl. ⁷ Identification code FI Theme coat II (Reference) A61K 7/08 A61K 7/08 7/11 7/11 7/42 7/42 7/48 7/48 31/16 31 / 16 A61P 17/00 A61P 17/00 17/16 17/16 43/00 111 43/00 111 (72) Inventor Yuya Sugai 2606 Akabane, Kakaicho, Haga-gun, Tochigi Pref. Person Mitsuru Sugiyama 2606, Kabane-cho, Akaga-cho, Haga-gun, Tochigi Prefecture, Japan (72) Inventor Yoshinori Nishizawa 2606, Kabashi-cho, Akaga-cho, Haga-gun, Tochigi Prefecture, Kao Corporation (72) Inventor of Kao Corporation (72) Inventor Yasushi Katayama, Sumida-ku, Tokyo Hana 2-1-3 F-term in Kao Corporation Research Laboratory (reference) 4C083 AA082 AA112 AB242 AB352 AB362 AC012 AC022 AC072 AC102 AC122 AC172 AC182 AC241 AC242 AC302 AC342 AC352 AC392 AC422 AC432 AC442 AC482 AC582 AC641 AC642 AC852 AD042 AD112 AD152 AD162 AD172 AD322 AD491 AD492 AD512 AD532 AD571 AD572 4C206 AA01 AA02 AA03 GA03 GA25 MA01 MA03 MA04 MA06 MA83 NA14 ZA89 ZC02

Claims (7)

[Claims] 1. The following general formula (1): (Wherein, R ^1a and R ^1b are the same or different and each have 1 to 2 carbon atoms.
R ^2a and R ^2b are the same or different and represent a divalent hydrocarbon group having 1 to 6 carbon atoms, and R ³ is the same or different and represent a divalent hydrocarbon group having 2 to 6 carbon atoms. Represents a hydrogen group,
n shows the number of 1-100. An external preparation composition containing a diamide derivative represented by the formula: 2. The following general formula (1): (Wherein R ^1a and R ^1b are the same or different and each have 1 to 2 carbon atoms)
R ^2a and R ^2b are the same or different and represent a divalent hydrocarbon group having 1 to 6 carbon atoms, and R ³ is the same or different and represent a divalent hydrocarbon group having 2 to 6 carbon atoms. Represents a hydrogen group,
n shows the number of 1-100. An external preparation composition comprising the diamide derivative represented by the formula) and a lipid component between keratinocytes. 3. The keratin intercellular lipid component is at least one selected from ceramides, pseudoceramide, glycosphingolipids, sphingolipids, sphingosine and its derivatives, sphingnin and its derivatives, higher fatty acids and cholesterol and its derivatives. 3. The external preparation composition according to claim 2, wherein 4. The composition according to claim 1, which is a cosmetic.
Item 3. The external preparation composition according to Item. 5. The following general formula (1): (Wherein R ^1a and R ^1b are the same or different and each have 1 to 2 carbon atoms)
R ^2a and R ^2b are the same or different and represent a divalent hydrocarbon group having 1 to 6 carbon atoms, and R ³ is the same or different and represent a divalent hydrocarbon group having 2 to 6 carbon atoms. Represents a hydrogen group,
n shows the number of 1-100. A humectant comprising a diamide derivative represented by the formula (1) as an active ingredient. 6. The following general formula (1): (Wherein R ^1a and R ^1b are the same or different and each have 1 to 2 carbon atoms)
R ^2a and R ^2b are the same or different and represent a divalent hydrocarbon group having 1 to 6 carbon atoms, and R ³ is the same or different and represent a divalent hydrocarbon group having 2 to 6 carbon atoms. Represents a hydrogen group,
n shows the number of 1-100. A skin barrier function enhancer comprising a diamide derivative represented by the formula (1) as an active ingredient. 7. The following general formula (1 ′): (Wherein R ^{1a ′} and R ^{1b ′} are the same or different and each have 4 to 4 carbon atoms)
R ^2a and R ^2b are the same or different and represent a divalent hydrocarbon group having 1 to 6 carbon atoms;
R ³ is the same or different and represents a divalent hydrocarbon group having 2 to 6 carbon atoms, and n represents a number of 1 to 100. A) a diamide derivative represented by the formula: