JP2005306886A - External agent composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an external agent composition, basically improving the water retaining ability and barrier functions of the horny layer, excellent in miscibility and mixing stability and capable of being efficiently prepared at a low cost. <P>SOLUTION: This external agent composition, a humectant and a skin barrier function reinforcing agent, contain each a diamide derivative represented by formula (1) (wherein, R<SP>1a</SP>and R<SP>1b</SP>are the same or different and represent each a 1-23C branched chain hydrocarbon; R<SP>2a</SP>and R<SP>2b</SP>are the same or different and represent each a 1-6C divalent hydrocarbon; R<SP>3</SP>s are the same or different and represent each a 2-6C divalent hydrocarbon; and (n) stands for 1 to 100). <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a compound that exhibits an effect of improving rough skin by maintaining a normal barrier function of the stratum corneum and improving water retention, and an external preparation composition containing the same.

  When the moisture retention ability and barrier function of the stratum corneum are reduced due to various internal causes or external causes, various skin troubles such as promoting rough skin and aging are caused. Moreover, in the rough skin symptom seen in various skin diseases such as atopic dermatitis, psoriasis and psoriasis, a decrease in water retention ability and barrier function of the stratum corneum is recognized. Therefore, the maintenance and reinforcement of the stratum corneum's ability to retain moisture and the barrier function are very important in conducting healthy daily life.

  Under such circumstances, the applicant of the present invention is a skin containing an amide derivative represented by the following general formula (2) as an external preparation for skin having an effect of essentially improving (maintaining, reinforcing) the barrier function of the stratum corneum. A patent application was filed for the topical preparation for external use (Patent Document 1).

(In the formula, R ^a represents a linear or branched saturated or unsaturated hydrocarbon group having 10 to 40 carbon atoms, and R ^b represents a linear or branched divalent hydrocarbon group having 3 to 39 carbon atoms. 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.)

However, such amide derivatives bring about the above-mentioned excellent effects, but the solubility and stability with respect to the base are not necessarily sufficient. There was still room for improvement. In addition, the production of these amide derivatives requires a multi-step reaction, which inevitably increases the production cost.
JP-A-4-128256

  An object of the present invention is to provide an external preparation composition that substantially improves the moisture retention ability and barrier function of the stratum corneum and is excellent in blending and blending stability and can be produced efficiently and inexpensively. .

  When the present inventors further examined the amide derivative, the diamide derivative represented by the following formula (1) has an action of enhancing the water retention ability and an improvement of the barrier function of the stratum corneum, and has excellent blendability and blending stability. And was found to be useful as an external preparation composition having an effect of preventing and improving skin troubles such as rough skin and a hair protecting effect.

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

Wherein R ^1a and R ^1b are the same or different and represent a branched hydrocarbon group having 4 to 23 carbon atoms, and R ^2a and R ^2b are the same or different and are divalent hydrocarbons having 1 to 6 carbon atoms. And 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.)
An external preparation composition containing the diamide derivative represented by the formula, an external preparation composition containing the diamide derivative and a keratinocyte lipid component, a moisturizer and a skin barrier function reinforcing agent containing the diamide derivative as active ingredients. Is.

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

(Wherein R ^{1a ′} and R ^{1b ′} are the same or different and represent a branched hydrocarbon group having 4 to 23 carbon atoms, and R ^2a and R ^2b are the same or different and are divalent carbon atoms having 1 to 6 carbon atoms. A 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 diamide derivative represented by these is provided.

  The diamide derivative (1) of the present invention permeates the lipid layer between the stratum corneum and improves (maintains / reinforces) the water retention ability and barrier function of the stratum corneum, and acts to enhance the protective effect by penetrating into the hair. As well as having good solubility in the base and excellent stability. Therefore, the external preparation composition, moisturizing agent and skin barrier function reinforcing agent of the present invention exhibit effects such as prevention and treatment of rough skin, prevention of skin aging, improvement of hair feel, prevention and improvement of scalp roughness, It is useful as a pharmaceutical, cosmetic, and quasi-drug with excellent stability. Furthermore, the external preparation composition of the present invention can be produced efficiently and inexpensively.

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 preferably a linear or branched alkyl group or alkenyl group having 5 to 17 carbon atoms, Furthermore, it is preferable that R ^1a and R ^1b are the same. Particularly preferred hydrocarbon groups include pentyl, heptyl, nonyl, undecyl, tridecyl, pentadecyl, heptadecyl, 1-ethylheptyl, 2,4,4-trimethylpentyl, 1-heptyldecyl, isoheptadecyl, methyl branched isoheptadecyl, 8-heptadecenyl, 8 , 11-heptadecadienyl group and the like.

Here, the compound represented by the general formula (1 ′) in which R ^1a and R ^1b are branched hydrocarbon groups having 4 or more carbon atoms is a novel compound.

The divalent hydrocarbon group having 1 to 6 carbon atoms represented by R ^2a and R ^2b is preferably a linear or branched alkylene group having 2 to 6 carbon atoms, and R ^2a and R ^2b are the same. The case is preferred. Particularly preferred divalent hydrocarbon groups include ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, 1-methylethylene, 2-methylethylene groups, etc. Among them, 1-methylethylene and 2-methylethylene groups are preferred. Further preferred.

The divalent hydrocarbon group having 2 to 6 carbon atoms represented by R ³ is preferably a linear or branched alkylene group having 2 to 6 carbon atoms, among which ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene 1-methylethylene, 2-methylethylene group, 2,2-dimethyltrimethylene and the like are preferable, and ethylene, 1-methylethylene and 2-methylethylene group are particularly preferable.

  Moreover, as n, the number of 1-50 is preferable, the number of 1-10 is more preferable, and the number of less than 4 is especially preferable.

Preferred examples of the diamide derivative (1) include compounds in which R ^1a , R ^1b , R ^2a , R ^2b , R ³ and n in the general formula (1) are preferably combined with the groups shown above. Of these, 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 have a low melting point and are excellent in compounding properties. It is preferable compared with the compound comprised.
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, it can be produced efficiently and inexpensively by the following production method.

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

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

  The conditions for this reaction include a dehydrating agent such as dicyclohexylcarbodiimide, an alkali metal hydroxide such as potassium hydroxide and sodium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, and an alkali metal carbonate such as potassium carbonate. In the presence or absence of bases such as alkaline earth metal carbonates such as calcium carbonate, alkali metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, tertiary amines such as triethylamine, pyridine, The reaction is preferably performed at room temperature to 300 ° C. under a reduced pressure of normal pressure to 1.3 Pa. At this time, it is preferable to use the carboxylic acid (4a) and / or (4b) or a reactive derivative thereof in excess, that is, 2 equivalents or more with respect to the diamine (3). However, it is preferable because the reaction proceeds quickly. The diamide derivative (1) thus obtained can also be purified by known methods such as washing with water, liquid-liquid distribution, column chromatography, distillation, crystallization, recrystallization and powder treatment.

  Examples of the diamine (3) include polyoxyethylene diamine, polyoxypropylene diamine, and polyoxyethylene-oxypropylene diamine. Specific examples thereof include Jeffamine (“JEFFAMINE” (registered trademark), Huntsman ( HUNTSMAN CORPORATION)) polyoxyalkylene diamines.

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

  In the present invention, when a water-soluble humectant selected from a polyhydric alcohol, an organic acid or a salt or derivative thereof and a plant extract is combined, it is possible to synergistically increase the water retention capacity of the stratum corneum.

  Examples of the polyhydric alcohol include polyglycerin such as glycerin, diglycerin, triglycerin, 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 reducing alcohol, sorbit, polyoxyalkylene alkyl glucoside and the like. Of these, glycerin, 1,3-butylene glycol, propylene glycol, and dipropylene glycol are particularly preferable.

  Two or more polyhydric alcohols may be used in combination. The content in the external preparation composition of the present invention is 0.001 to 50% by weight (hereinafter, simply expressed as%), preferably 0.01 to 40%, particularly preferably 0.1 to 30%. It is possible to synergistically increase the water retention capacity of the stratum corneum.

  Examples of organic acids and organic acid derivatives include glycolic acid, lactic acid, citric acid, 2-hydroxyoctanoic acid and other oxycarboxylic acids having 2 to 28 carbon atoms; succinic acid, fumaric acid, maleic acid, malonic acid, 1,3- C2-C12 dicarboxylic acids such as propanedicarboxylic acid; amino acids such as aspartic acid, asparagine, glycine, glutamic acid, glutamine, γ-aminobutyric acid, arginine, cysteine, alanine and the like; octyl succinate, methyl maleate, etc. Dicarboxylic acid monoesters of: nicotinic acid, methyl nicotinate, ethyl nicotinate, benzyl nicotinate, nicotinamide, tocopherol nicotinate, quinolinic acid, pyridine-3,5-dicarboxylic acid, nicotinamide adenine dinucleotide phosphate ( NADP), mononuclear nicotinate Fault, nicotinyl alcohol, nicotinic acid or a salt thereof, such as tartaric nicotinyl alcohol or its derivatives and the formula (5)

The sterin derivative represented by these is mentioned.

As the above-mentioned sterine derivative, those having 1 to 5 in general formula (5), R ⁶ is preferably hexadecenyl and octadecenyl, and R ⁵ is preferably cholesteryl or cytosteryl.

  As such organic acid and organic acid derivative, α-hydroxycarboxylic acid, amino acid, nicotinic acid and derivatives thereof are preferable, and glycolic acid, lactic acid, citric acid, succinic acid, aspartic acid, glycine, arginine, nicotinic acid amide Particularly preferred are tocopherol nicotinate and glycine betaine.

  Examples of the organic acid salt include potassium, sodium, magnesium, calcium, aluminum, basic amino acid salts such as lactic acid, citric acid, and succinic acid. When the organic acid has a basic group, for example, Acid addition salts such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and the like can be mentioned.

  Two or more organic acids or salts or derivatives thereof may be used in combination. The content in the external preparation composition of the present invention is preferably 0.0001 to 10%, particularly preferably 0.001 to 5%.

Examples of the plant extract include those described in JP-A-9-165313. Of these, eucalyptus, hops, ginger, kyoto, gumpiroki, wild rose, pearl oysters, lilies, pearl barley, cattails, loquat, gardenia, ginseng, bonnet, birch, amacha, clove, safflower, burdock, iris, and clara Extracts, 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 kinds of plant extracts may be used in combination. The content in the external preparation composition of the present invention is preferably 0.0001 to 10%, particularly preferably 0.0001 to 5% in terms of dry solid content.

  In the present invention, by combining keramide intercellular lipid components selected from ceramides, pseudoceramides, glycosphingolipids, sphingophospholipids, sphingosine and derivatives thereof, sphinganine and derivatives, higher fatty acids, cholesterol and derivatives thereof, and the like. It is possible to synergistically increase the barrier function of the stratum corneum.

Ceramides include natural ceramides extracted and purified from the brain and skin and synthetic ceramides synthesized by microbiological or chemical methods.
Examples of natural ceramides 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 the synthetic ceramide, for example, methods described in JP-A-59-7118, JP-A-4-342553, WO93 / 22281 and the like can be used.
On the other hand, pseudoceramide can be produced according to the methods described in, for example, JP-A-62-228048 and JP-A-63-216852. Particularly preferred as pseudoceramide is a compound represented by the following formula (6).

(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 sphingoglycolipid and sphingophospholipid, there are naturally derived ones and synthetic ones as well as the ceramides described above. Examples of the sphingoglycolipid include those in which the constituent sugar is composed of glucose, mannose, galactose, glucuronic acid, glucosamine, and the like, and also include cerebroside and sulfate thereof. Examples of sphingophospholipids include sphingomyelin.

  Sphingosines preferably used in combination with ceramides, pseudoceramides, glycosphingolipids, and sphingophospholipids are disclosed in JP-A-5-85924 and in JP-A-6-271446. The compound represented by the general formula (7) and the compound represented by the general formula (8) disclosed in JP-A-5-194185 are preferred.

  The sphingosines disclosed in JP-A-5-85924 are sphingosine (sphingenin), dihydrosphingosine (sphinganine), phytosphingosine, dehydrosphingosine, dehydrophytosphingosine, sphingadienin and their N-methyl or N , N-dimethyl form and the like. The carbon number of the hydrocarbon group of these compounds is preferably 12 to 24, and may be either linear or branched saturated or unsaturated.

  Further, the compound (7) disclosed in JP-A-6-271446 is

  Further, the compound (8) disclosed in JP-A-5-194185 is

(In the formula, 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 are each hydrogen. An atom or a hydrocarbon group having 1 to 10 carbon atoms which may be substituted by one or more hydroxyl groups)
It is represented by

  As the higher fatty acid, those having 12 or more carbon atoms, particularly those having 12 to 24 carbon atoms are preferable, and examples include myristic acid, palmitic acid, palmitooleic acid, stearic acid, oleic acid, linoleic acid, and behenic acid. Moreover, you may mix | blend the monoglyceride, diglyceride, and triglyceride which are rich in those higher fatty acids.

  As the cholesterol ester, those consisting of higher fatty acids having 12 or more carbon atoms, particularly 12 to 24 carbon atoms, are preferred, such as cholesterol palmitate, cholesterol isostearate, N-lauroyl-L-glutamate (cholesterol, 2-octyldodecyl), lanolin. Examples include fatty acid cholesterol and macadamian nut oil fatty acid cholesterol.

Two or more keratinocyte lipid components may be used in combination. The content in the external preparation composition of the present invention is preferably 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 an emulsified skin external preparation, and is based on a liquid hydrocarbon such as squalane. In the case of an oily external preparation for skin, 0.01 to 50% of the total composition is preferable, and in any case, 0.01 to 20% is particularly preferable. It is preferable to contain 0.1 to 20% especially for prevention and improvement of rough skin.

The external preparation composition of the present invention is broadly classified into medicinal skin external preparations and cosmetics in its usage form, but is preferably used as cosmetics, particularly skin cosmetics.
Examples of the medicinal skin external preparation include various ointments containing medicinal ingredients. The ointment may be either an oil-based base or an oil-in-water or water-in-oil emulsion base. Examples of the oily base include vegetable oils, animal oils, synthetic oils, fatty acids, and natural or synthetic glycerides. As the medicinal component, for example, an analgesic / anti-inflammatory agent, an antipruritic agent, a bactericidal disinfectant, an astringent agent, an emollient, a hormone agent 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, moisturizers generally used as cosmetic components, Ultraviolet absorbers, whitening agents, wrinkle improving agents, alcohols, chelating agents, pH adjusting agents, preservatives, thickeners, pigments, fragrances and the like can be contained in any combination.

  As cosmetics, various forms such as water-in-oil or oil-in-water emulsified cosmetics, creams, cosmetic emulsions, lotions, oily cosmetics, lipsticks, foundations, bathing agents, skin cleansing agents, nail care agents, Examples include hair cosmetics. Examples of hair cosmetics include hair tonics, hair styling agents, hair rinses, hair treatments, hair conditioners, hair styling agents, shampoos, hair nourishing agents, hair restorers and the like.

  In the external preparation composition of the present invention, a medicinal skin external preparation or skin cosmetic contains a surfactant such as a nonionic surfactant, an anionic surfactant, a cationic surfactant, or an amphoteric surfactant. Can do. Among 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 preferable. The content is preferably 0.01 to 20%, particularly preferably 0.1 to 10% in the composition.

  When used as a hair cosmetic, the content of the diamide derivative (1) is, for example, 0.001 to 5% for shampoos and the like, and 0.1 for rinses, treatments, conditioners, styling agents and the like. About 0.01 to 5% is preferable for ˜20%, hair liquid, hair tonic and the like.

  The hair cosmetic may contain an anionic surfactant, a cationic surfactant, a nonionic surfactant, a surfactant such as an amphoteric surfactant, and other components generally used in hair cosmetics. 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 active agent. The content thereof is preferably 5 to 30%, particularly 10 to 20% in the composition.

  When the cosmetic composition of the present invention is a hair rinse, a conditioner, a hair treatment, or a hair styling agent, a cationic surfactant such as mono- or di-long chain alkyl quaternary ammonium salt, polyoxy Nonionic surfactants such as ethylene alkyl or alkenyl ether, and fats and oils such as liquid paraffin can be contained. The content of the cationic and nonionic surfactant is preferably 0.1 to 50%, particularly preferably 0.5 to 20% in the composition.

  Furthermore, when hair cosmetics are hair liquid, hair tonic, etc., nonionic surfactants, such as polyoxyethylene, can be contained. The nonionic surfactant is preferably contained in the total composition in an amount of 0.01 to 20%, particularly 0.1 to 5%.

Production Example 1
Production of compound (A)

  A flask equipped with a stirrer, a nitrogen inlet tube and a distillation apparatus was charged with 317 g of caprylic acid (Lunac 8-98 (E) manufactured by Kao), and Jeffamine D-230 (manufactured by Huntsman) at 220 ° C. under nitrogen flow with stirring. ) 228 g was added dropwise over 2.5 hours. The mixture was aged for 5 hours under the same conditions. The above dripping and ripening were carried out while distilling off by-produced water by carrying out under a nitrogen stream. After completion of the reaction, molecular distillation (160-210 ° C., 0.5 Pa) was performed to obtain 262 g of the title compound (A). The physical properties of the obtained compound (A) are as follows.

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 = 7.5 Hz), 3.00-3.75 (m), 4.00 -4.30 (m), 5.60-6.10 (m).

Production Examples 2-11
The following compounds (B) to (k) were produced 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). The physical properties of each diamide derivative are shown together in Table 1 and Table 2.

Test example 1
The preparations for external use of the present invention (products of the present invention) having the compositions shown in Tables 3 to 5 containing the diamide derivatives produced in Production Examples 1 to 11 were prepared, respectively, and these external preparations were subjected to the following method. Skin moisture transpiration and transdermal absorption were measured and evaluated. The results are shown in Table 6 below.
(Test method)

  Wister male rats were bred only on diets that did not contain essential fatty acids, and rats with symptoms of essential fatty acid deficiency were used in this study. After carefully shaving the back of these essential fatty acid deficient rats, the external preparation composition was applied once a day for 12 days. In addition, 5 animals per group were used for this test for each external preparation for evaluation. Three days after the application was completed, the following items were measured and evaluated.

(1) Transcutaneous moisture transpiration The transdermal moisture transpiration of the back of the test rat was measured with a tevameter. The transdermal moisture transpiration inhibitory effect was determined according to the following formula.
Inhibition degree of transdermal moisture transpiration of the product of the present invention =
Percutaneous moisture transpiration of the comparison product 1 applied rat-Transdermal water transpiration of the rat applied with the present invention (g / m ² / hr)

(2) Percutaneous absorption The back skin of the test rat was cut out and fixed to the percutaneous absorption chamber with the epidermis side up. The lower receiver was filled with a phosphate buffered saline solution, and a phosphate buffered saline solution containing 37 KBq of ¹⁴ C-salicylic acid was added to the upper part of the epidermis and allowed to stand. After 19 hours, a certain amount of phosphate buffered saline was withdrawn from the lower receiver, and the radioactivity of ¹⁴ C-salicylic acid that had permeated was measured. The percutaneous absorption inhibitory effect was determined according to the following formula.
Degree of percutaneous absorption suppression of the product of the present invention =
Comparative product 1 percutaneous absorption of rats coated with this product-percutaneous absorption of rats coated with the present invention (dpm)

  The inventive products 1 to 11 had an excellent effect of suppressing transdermal moisture transpiration and transdermal absorption compared with the comparative product 1, and were excellent in the rough skin improvement effect.

Test example 2
The preparations for external use of the present invention (products of the present invention) of the present invention having the compositions shown in Table 7 and Table 8 containing diamide derivatives were prepared, respectively, and percutaneous moisture transpiration and skin conductance were measured and evaluated for these external preparations by the following methods. did. Further, as a comparison, the same measurement and evaluation was performed for an external preparation composition (comparative product 2) containing petrolatum, which is known to have high skin occlusive properties and is used in medicinal skin external preparations and skin cosmetics. . The results are shown in Table 9.

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

The transdermal moisture transpiration was measured with a tevameter. The transdermal moisture transpiration inhibitory effect was determined according to the following formula.
Inhibition degree of transdermal moisture transpiration of the product of the present invention =
Percutaneous moisture transpiration of base application part-Transdermal moisture transpiration of application part of the present invention (g / m ² / hr)

(2) Water content of stratum corneum The water content of the stratum corneum was measured with a skin conductance meter. A higher conductance means a higher moisture content in the stratum corneum. According to the following formula, the improvement effect of the water retention ability of the stratum corneum was determined.
Improvement in water retention capacity of the product of the present invention =
Conductance of the application part of the present invention-Conductance of the base application part (μS)

  The inventive products 12 to 17 were superior to the comparative product 2 in the effect of increasing the water content of the stratum corneum, the effect of suppressing transdermal moisture transpiration, and the effect of improving rough skin.

Test example 3
External preparation compositions of the present invention (products of the present invention) having the compositions shown in Table 10 and Table 12 were prepared, and transdermal moisture transpiration, skin conductance, and rough skin were evaluated for these external preparations. Moreover, the same evaluation was performed also about the external preparation composition (comparative product 2) containing petrolatum for comparison. The results are shown in Table 11 and Table 13.
(Test method)
(1) Transcutaneous moisture transpiration Evaluation was conducted in the same manner as in Test Example 2.
(2) Water content of stratum corneum Evaluation was performed 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: Does not recognize rough skin 1: Appears faint rough skin 2: Approves rough skin 3: Appears slightly rough skin

  The inventive products 13 and 18 to 26 were superior to the comparative product 2 in the effect of suppressing transdermal moisture transpiration of the stratum corneum and the effect of improving rough skin.

  Inventions 13 and 27 to 33 were excellent in the effect of increasing the amount of water in the stratum corneum and the effect of improving rough skin as compared with Comparative Product 2.

Test example 4
The hair rinses of the present invention having the compositions shown in Table 14 and Table 15 containing the diamide derivatives (Products of the present invention) were prepared, and the hairiness and feel after treatment with these hair rinses were evaluated by the following criteria using five panelists. did. The results are shown in Table 16 and Table 17.

-2: Bad -1: Slightly bad 0: Cannot say +1: Slightly good +2: Good

  The inventive products 34 to 38 were superior to the comparative product 3 in improving the crispness of the hair and improving the feel of the hair.

Example 1
Skin lotions with the formulation shown in Table 18 were produced according to a conventional method. The obtained skin lotion exhibited an excellent effect of preventing and improving rough skin. In addition, the compounds (A), (C), (D), (E), (G), and (K) were excellent in blendability and blending stability.

Example 2
O / W creams with the formulation shown in Table 19 were produced according to a conventional method. The obtained O / W cream showed an excellent effect of preventing and improving rough skin. The compounds (A), (C), (D), (E), (G), and (K) were excellent in blendability and blending stability.

Example 3
A shampoo was produced according to a conventional method with the formulation shown in Table 20. This shampoo improved the feel of the hair and prevented and improved scalp roughness. The compounds (A), (C), (D), (E), (G), and (K) were excellent in blendability and blending stability.

Example 4
A hair liquid composition with the formulation shown in Table 21 was produced according to a conventional method. The obtained hair liquid composition imparted excellent style retention and good feel to the hair. The compounds (A), (C), (D), (E), (G), and (K) were excellent in blendability and blending stability.

Example 5
A night cream having the following composition was prepared. The obtained night cream had the effect of recovering and reinforcing the lowering of the barrier function of the skin stratum corneum, further enhancing the water retention ability of the stratum corneum, and exhibiting the effect of preventing and improving rough skin. The compounds (A), (C), (D), (E), (G), and (K) were excellent in blendability and blending stability.

Example 6
A sunscreen emulsion having the composition shown below was prepared. The obtained sunscreen emulsion has the effect of recovering and reinforcing the decrease in the barrier function of the skin stratum corneum, further enhancing the water retention ability of the stratum corneum, and exhibiting the effect of preventing and improving rough skin. The compounds (A), (C), (D), (E), (G), and (K) were excellent in blendability and blending stability.

Claims (7)

The following general formula (1):
Wherein R ^1a and R ^1b are the same or different and represent a branched hydrocarbon group having 4 to 23 carbon atoms, and R ^2a and R ^2b are the same or different and are divalent hydrocarbons having 1 to 6 carbon atoms. And 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 external preparation composition containing the diamide derivative represented by these. The following general formula (1):
Wherein R ^1a and R ^1b are the same or different and represent a branched hydrocarbon group having 4 to 23 carbon atoms, and R ^2a and R ^2b are the same or different and are divalent hydrocarbons having 1 to 6 carbon atoms. And 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.)
An external preparation composition containing a diamide derivative represented by the formula and a keratinocyte lipid component.   3. The keratin intercellular lipid component is at least one selected from ceramides, pseudoceramides, glycosphingolipids, sphingophospholipids, sphingosine and derivatives thereof, sphinganine and derivatives thereof, higher fatty acids and cholesterol and derivatives thereof. Topical preparation composition.   It is a cosmetic, The external preparation composition of any one of Claims 1-3. The following general formula (1):
Wherein R ^1a and R ^1b are the same or different and represent a branched hydrocarbon group having 4 to 23 carbon atoms, and R ^2a and R ^2b are the same or different and are divalent hydrocarbons having 1 to 6 carbon atoms. And 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 humectant comprising a diamide derivative represented by the formula: The following general formula (1):
Wherein R ^1a and R ^1b are the same or different and represent a branched hydrocarbon group having 4 to 23 carbon atoms, and R ^2a and R ^2b are the same or different and are divalent hydrocarbons having 1 to 6 carbon atoms. And 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 skin barrier function reinforcing agent which uses the diamide derivative represented by these as an active ingredient. The following general formula (1 ′):
(Wherein R ^{1a ′} and R ^{1b ′} are the same or different and represent a branched hydrocarbon group having 4 to 23 carbon atoms, and R ^2a and R ^2b are the same or different and are divalent carbon atoms having 1 to 6 carbon atoms. A 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 diamide derivative represented by these.