JPH0459285B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention relates to a skin preparation for external use, and more particularly, to a skin preparation for external use that can improve the moisture retention capacity of the stratum corneum and improve rough skin. [Prior Art] It has been known that the moisture in the stratum corneum is important for moisturizing the skin and making it soft. The retention of moisture is said to be due to water-soluble components contained in the stratum corneum, such as free amino acids, organic acids, urea, or inorganic ions, and these substances may be used alone or in combination in medicated skin preparations. Alternatively, it is used in cosmetics to improve or prevent rough skin. In addition, many other moisturizing substances that have a high affinity for water have been developed and are used for similar purposes. [Problem to be solved by the invention] However, when these moisturizing substances are applied to the skin, their action is to supply moisture to the stratum corneum on the skin, and the effect is temporary. However, it did not fundamentally improve the water retention ability of the stratum corneum or essentially prevent or cure rough skin. [Means for Solving the Problems] Under these circumstances, the present inventors conducted intensive research focusing on interkeratinocyte lipids in order to solve the above problems, and found that the following general lipids, which are easily available in large quantities, The combination of the novel amide derivative represented by the formula () and the lipid present between corneocytes has the effect of fundamentally improving the water retention ability of the stratum corneum, and that the combination of the above mixture with a surfactant improves the water retention ability of the stratum corneum. They discovered that the effect could be further increased and completed the present invention. That is, the present invention comprises the following components (A) and (B) (A) General formula () (In the formula, R ³ is a linear or branched saturated or unsaturated hydrocarbon group having 10 to 26 carbon atoms,
( ^R4 represents a linear or branched saturated or unsaturated hydrocarbon group having 9 to 25 carbon atoms); (B) cholesterol, cholesterol fatty acid ester, fatty acid, triglyceride; The present invention provides an external skin preparation characterized by containing one or more of , cerebroside, or phospholipid. Although the amide derivative () used in the present invention is a new compound, it can be obtained by a known method [for example, Polytechnic Journal of Chemistry (Pol.J.
Chem.) 52 , 1059 (1978); 52 , 1283 (1978); JP 54-117421, 54-144308, 54-
147937].
That is, it can be produced by reacting a compound () obtained from glycidyl ether and ethanolamine with a fatty acid methyl ester according to the reaction formula shown below. (In the formula, R ³ and R ⁴ are the same as above.) In this way, the amide derivative () can be easily produced in large quantities from inexpensive and easily available raw materials. For cholesterol, the following formula () The derivative represented by is most preferred, but any derivative can be used as long as the hydroxyl group at the 3-position remains. For cholesterol fatty acid ester, the formula () (In the formula, R ⁵ represents a straight chain or branched chain saturated or unsaturated hydrocarbon group having 1 to 25 carbon atoms which may be substituted with one or more hydroxyl groups). Any derivative can be used as long as the 3-position ester group remains. The fatty acid has the general formula () R ⁶ -COOH () (where R ⁶ is a linear or branched saturated or unsaturated hydrocarbon having 1 to 25 carbon atoms that may be substituted with one or more hydroxyl groups). (representing a group) can be used, but those having 14 to 18 carbon atoms can be used.
Straight chain saturated or unsaturated fatty acids are most suitable. General formula () for triglyceride (In the formula, R ⁷ , R ⁸ , and R ⁹ represent a straight chain or branched chain saturated or unsaturated hydrocarbon group having 1 to 25 carbon atoms that may be substituted with one or more hydroxyl groups.) Things can be used. Cerebroside is a complex lipid made by adding sugar to ceramide, and has the general formula () (In the ^{formula ,} (represents a hydrogen group). Phospholipids can be broadly classified into glycerophospholipids, which are glycerin derivatives, and sphingophospholipids, which are ceramide derivatives. Phospholipids included in either of these can be used in the present invention. The blending ratio of component (A) and component (B) in the external skin preparation of the present invention is preferably 8:2 to 2:8 by weight. To blend these, it is preferable to mix both in the above ratio, heat and melt, then cool to form a paste or solid, which is then added to the other ingredients, but it is also preferable to add each separately. Good too. The amount of the mixture of component (A) and component (B) in the skin preparation of the present invention is not particularly limited, but in the case of an emulsion-type skin preparation, it is usually 0.01 to 60% by weight of the total composition.
(hereinafter simply expressed as %), particularly preferably 0.1 to 30%,
In the case of oil-based external skin preparations based on liquid hydrocarbons such as squalane, 1 to 90%, especially 5 to 50%
% is preferred. As the surfactant used in combination to further increase the effects of the present invention, any of nonionic surfactants, anionic surfactants, and amphoteric surfactants can be used, but especially nonionic surfactants is suitable. Examples of nonionic surfactants include polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene fatty acid ester, sorbitan fatty acid ester,
polyoxyethylene sorbitan fatty acid ester,
Examples include fatty acid monoglyceride and glyceryl ether. Among them, the following general formula () (In the formula, R ¹⁰ represents an alkyl group having 8 to 24 carbon atoms) Glyceryl ^ether represented by the following formula () (In the formula, p is an integer of 4 to 10, q is an integer of 5 to 11, and has a distribution where p+q=11 to 17, with p=7 and q=8 as the vertices) . The amount of surfactant added is 0.01 to 20% of the total composition.
Particularly preferred is 0.1 to 5%. The skin external preparations of the present invention are broadly classified into medicated skin external preparations and cosmetics in terms of their usage forms. Examples of medicated skin external preparations include various ointments containing medicinal ingredients. Ointments include those based on oily bases, oil/
It may be based on water or water/oil type emulsion base. The oily base is not particularly limited and includes, for example, vegetable oils, animal oils, synthetic oils, fatty acids, natural or synthetic glycerides, and the like. There are no particular limitations on the medicinal ingredients, and for example, analgesic and antiinflammatory agents, antipruritic agents, sterilizing disinfectants, astringents, emollients, hormonal agents, and the like can be used as appropriate. When used as a cosmetic, in addition to the essential ingredients, oils, moisturizers, ultraviolet absorbers, alcohols, chelates, PH adjusters, preservatives, thickeners, Any combination of dyes, fragrances, etc. can be blended. Cosmetics can be used in various forms, such as water/oil,
It can be used as skin cosmetics such as oil/water type emulsified cosmetics, creams, cosmetic emulsions, lotions, oil-based cosmetics, lipsticks, foundations, skin cleansers, hair tonics, hair conditioners, hair tonics, hair growth agents, etc. . [Action] Although the details of the mechanism of action of the mixture of component (A) and component (B) in the topical skin preparation of the present invention have not been completely elucidated, it is believed that it builds a lipid bilayer together with water between corneocytes. It is thought that it exerts the moisture retention function of the stratum corneum. [Effects of the Invention] Since the skin external preparation of the present invention contains a mixture of component (A) and component (B) that have the above-mentioned effects, it exhibits excellent improvement and prevention effects on rough skin. can do. [Example] Next, reference examples and examples will be given and explained. Reference Example 1 N-(2-hydroxy-3-hexadecyloxypropyl)-N-2-hydroxyethylhexadecanamide [In formula (), R ³ = C ₁₆ H ₃₃ ,
R ⁴ = C ₁₅ H ₃₁ ] Synthesis of (a): 1637 g (26.8 mol) of ethanolamine and ethanol were placed in a 54-necked flask equipped with a stirrer, a dropping funnel, a thermometer, a reflux condenser, and a nitrogen inlet tube. 327g (7.11mol) was added under nitrogen atmosphere.
While heating and stirring at 80°C, 400 g (1.34 mol) of hexadecyl glycidyl ether was added dropwise over 3 hours. After completion of the dropwise addition, the mixture was further heated and stirred for 30 minutes under the same conditions, and then a distillation apparatus was attached, and ethanol and unreacted ethanolamine were distilled off under reduced pressure (79-81°C/20 Torr). 80℃／20Torr
While heating and stirring, 362.3 g (1.34 mol) of methyl hexadecanoate was added dropwise to this over 3 hours.
After the addition was completed, the mixture was further heated and stirred for 1 hour under the same conditions to obtain 801 g of a pale yellow crude product. By recrystallizing this once from hexane and twice from ethanol, the target compound (
a) 649 g (yield 81%) was obtained. Example 1 Preparation of a mixture of components (A) and (B): 60% by weight of compound (a) and 40% by weight of cholesterol [formula ()] are weighed into a glass screw cap sample bottle. Heat the sample bottle to 150℃ using a heating block, etc. When (a) and cholesterol are completely dissolved by heating, the heating is terminated and the mixture is left to cool in the air to obtain a paste-like mixture. Example 2 The mixture obtained in Example 1 was added to petrolatum (a).
A skin external preparation prepared by adding and blending the above mixture to Vaseline so that the amount of (a) is 15% by weight and the cholesterol is 10% by weight (product 1 of the present invention). In addition to this, a skin external preparation prepared by adding 4% by weight of glyceryl ether [in which R ¹⁰ is of the formula ()] (invention product 2), and vaseline (control)
The skin conductance and skin roughness were evaluated using the following method. The results are shown in Table 1. (Test method) Ten women between the ages of 20 and 50 who suffer from rough skin on their cheeks during the winter were used as subjects, and different samples were applied to the left and right cheeks once a day for two weeks. The next day after the two-week application was completed, the following tests were conducted. (1) Skin conductance After washing the face with warm water at 37℃ and resting for 20 minutes in a room with a temperature of 20℃ and humidity of 40%, the water content of the stratum corneum was measured using a skin conductance meter (manufactured by IBS). . As for the conductance value, the smaller the value, the rougher the skin, and if it is less than 5, the skin is severely rough.
On the other hand, if this value is 20 or higher, skin roughness is hardly observed. (2) Skin roughness score Skin roughness was observed with the naked eye and judged according to the following criteria. Scores were expressed as mean value ± standard deviation.

【table】 (result)

[Table] Example 3 Compound (a), cholesterol represented by formula (), and stearic acid [in formula (), R ⁶ =
C ₁₇ H ₃₃ ] was formulated as shown in Table 2 to produce an oil-in-water emulsion cosmetic, and using the same method as in Example 2, skin conductance and skin roughness were evaluated. The results are shown in Table 3.

【table】

[Table] Example 4 Cosmetic (emulsion) <Composition> Oil phase components: Macadamia nut oil 2.0 (wt%) Squalane 5.0 Stearic acid 1.0 Compound (a) 1.0 Soybean phospholipid 0.5 Glucocerebroside (cow brain extract)
0.5 Sorbitan monostearate 0.5 POE (60) hydrogenated castor oil 1.0 Water phase components: Glycerin 1.0 Propylene glycol 1.0 Methylparaben 0.3 Fragrance 0.1 Purified water Amount to make the total 100 <Manufacturing method> Mix the oil phase components and heat and dissolve. and keep at 70℃.
The aqueous phase components are similarly heated and mixed at 70°C, and the above-mentioned oil phase is added to the aqueous phase components and emulsified using an emulsifier.
The emulsion was cooled to a final temperature of 30°C using a heat exchanger and then filled into a container to prepare an emulsion.

Claims (1)

[Claims] 1st order components (A) and (B), (A) General formula () (In the formula, R ³ is a linear or branched saturated or unsaturated hydrocarbon group having 10 to 26 carbon atoms,
( ^R4 represents a linear or branched saturated or unsaturated hydrocarbon group having 9 to 25 carbon atoms); (B) cholesterol, cholesterol fatty acid ester, fatty acid, triglyceride; , one or more types of cerebrosides or phospholipids. 2 The blending ratio of component (A) and component (B) is 8:2 by weight.
The skin external preparation according to claim 1, wherein the ratio is 2:8. 3. The external preparation for skin according to claim 1, further comprising a surfactant.