JP5432470B2 - Ceramide solution and external preparation for skin - Google Patents

Description

  The present invention relates to a solution of ceramides.

Ceramide is contained in intercellular lipids in the horny layer of the skin and is a component that contributes to the skin barrier function. Ceramide is known as a component that is difficult to dissolve.
N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide is known as a similar substance to ceramide (Patent Document 1: Japanese Patent Laid-Open No. 63-228048). Although this substance is known to exhibit excellent improvement and prevention effects against rough skin, it is difficult to dissolve and various devices have been devised.

For example, a technique for dissolving a ceramide-like substance in a specific polyhydric alcohol fatty acid ester excluding triglyceride is known (Patent Document 2: Japanese Patent No. 3503834), but it is difficult to dissolve a ceramide-like substance in triglyceride. It was. Although a technique for dissolving a ceramide-like substance using an amphiphilic polymer and a specific oil is known (Patent Document 3: Japanese Patent No. 3779661), the use of an amphiphilic polymer is unavoidable and used. Sex is limited. Although a technique for stably dissolving a ceramide-like substance using sorbitan monolaurate is known (Patent Document 4: Japanese Patent Laid-Open No. 2005-8580), it is necessary to use sorbitan monolaurate at a high concentration, which is safe. There was a problem with sex.
In addition, as a technique for dissolving or dispersing ceramides, a technique for containing a monovalent lower alcohol, oil, and water (Patent Document 5: JP 2000-119178 A), an aliphatic alcohol and glyceryl monooleyl ether are contained. Technology (Patent Document 6: Japanese Patent Application Laid-Open No. 2003-12486), Technology for blending alkyl lactate (Patent Document 7: Japanese Patent Application Laid-Open No. 2003-40728), Technology containing dimer diol derivative (Patent Document 8: Japanese Patent Application Laid-Open No. 2004-2004) No. -131420), and a technique (Patent Document 9: Japanese Patent Laid-Open No. 2007-1950) containing a phospholipid and a higher alcohol that is liquid at room temperature is known. However, further improvement is required for the technique for dissolving ceramides.

Japanese Unexamined Patent Publication No. 63-228048 Japanese Patent No. 3503834 Japanese Patent No. 3779661 Japanese Patent Laying-Open No. 2005-8580 JP 2000-119178 A JP 2003-12486 A JP 2003-40728 A JP 2004-131420 A JP 2007-1950 A

  The purpose is to improve the solubility of ceramides.

  This invention improves the solubility of ceramides by combining with a fatty acid triglyceride and a phytosterol derivative. Examples of the ceramides of the present invention include ceramides, ceramide derivatives, and ceramide-like substances.

The main solving means of the present invention is as follows.
(1) Macadamia nut oil and
Ceramide consisting of ceramide 2, ceramide 3, tetraacetyl phytosphingosine, N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethyl hexadecanamide, trihydroxypalmitamide hydroxypropyl myristyl ether Any one ceramide selected from ceramide-like substances consisting of:
Dimerlinoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimerlinoleic acid di (isostearyl / phytosteryl), lauroylglutamate di (octyldodecyl / phytosteryl / behenyl), lauroylglutamate di (phytosteryl / octyldodecyl) Containing one or more phytosterol derivatives selected from
The oil solution whose compounding ratio of macadamia nut oil , ceramides, and a phytosterol derivative is 100: 0.02-0.2: 1-20.
(2) The oil solution according to (1), which does not contain sorbitan monolaurate or an amphiphilic polymer.
(3) An external preparation containing 0.5 to 5% by mass of macadamia nut oil , 0.001% by mass or more of ceramides and a phytosterol derivative,
Ceramide whose ceramide is ceramide 2 or ceramide 3, or tetraacetylphytosphingosine, N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide, trihydroxypalmitamide hydroxy Any one selected from ceramide-like substances consisting of propyl myristyl ether,
Phytosterol derivatives include dimer dilinoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimer dilinoleic acid di (isostearyl / phytosteryl), lauroyl glutamate di (octyldodecyl / phytosteryl / behenyl), lauroyl glutamate di (phytosteryl / One or more selected from octyldodecyl),
Furthermore, the skin external preparation characterized by the compounding ratio of macadamia nut oil , ceramides and phytosterol derivative in the external preparation for skin being 100: 0.02 to 0.2: 1 to 20.

It is possible to provide a ceramide solution in a stable dissolved state without precipitation of ceramides. It was clarified that the liquid phytosterol derivative at room temperature does not interfere with the dissolution of ceramides but acts as an auxiliary. The phytosterol derivative is effective when added in a small amount, and depending on the type, increasing the added amount tends to promote precipitation of ceramides. In particular, macadamia nut fatty acid phytosteryl has substantially good solubility in the range of fatty acid triglyceride: phytosterol derivative = 50: 1 to 10: 1, and promotes ceramide precipitation at 10: 1 or more. In addition, the solid phytosterol derivative did not improve the solubility just because the total amount of the oil was increased, but it was clearly shown that there was an appropriate ratio for stabilizing the ceramides.
In general, in order to improve the rough skin improvement effect by blending ceramides into a skin external preparation, a blending amount of 0.001% by mass or more is necessary. Since the oil solution of the present invention contains a high concentration of ceramides, by adding 0.5 to 5% by mass of fatty acid triglyceride to the external preparation for skin, it is possible to realize the formulation of 0.001% by mass or more of ceramides. Both a refreshing feeling of use and a rough skin improvement effect can be realized.
The present invention was able to dissolve high-concentration ceramides using fatty acid triglycerides and phytosterol derivatives as solvents without using sorbitan monolaurate and amphiphilic polymers used in the prior art. Accordingly, it is possible to provide an external preparation for skin that has high safety and can be freely designed for use.

Ceramide is an amide derivative that occupies about 50% of intercellular lipids present in human skin (horny layer). In normal skin, ceramide is produced in the process of keratinization, but ceramide in the stratum corneum decreases with age, so that it becomes easier to dry as the age increases, and the barrier function also decreases. Therefore, by adding ceramide to the cosmetic, the barrier function can be improved by improving the moisture retention.
In the present invention, an oil solution having an increased amount of dissolution using a compound of ceramides such as ceramide, a ceramide derivative and a ceramide-like substance has been developed. The low solubility of these substances is as described in the background art, and the solubility is ensured by using an unfavorable auxiliary agent for the skin such as sorbitan monolaurate. The solubility was increased without using an auxiliary agent. It was possible to dissolve at least 0.2% by weight.
Fatty acid triglyceride is used as a solvent for the ceramides used in the present invention. The ceramides to be dissolved are lipids (a kind of oil) and have a lipophilic group and a hydrophilic group in the structure, so that they can hold moisture. As a fatty acid triglyceride, macadamia nut oil, in particular, contains palmitooleic acid in an amount of about 25% and is preferable as an oil agent close to sebum.
Phytosterol was used as a bio-similar component in order to increase the affinity for the skin. When phytosterol was not blended, it was confirmed that the ceramides of the present invention could not be blended at high concentrations only with fatty acid triglycerides, while phytosterol derivatives were also confirmed to inhibit solubility unless the addition amount was appropriate. Depending on the type of phytosterol, 1 to 20 is suitable for the solvent 100. The phytosterol used in the present invention is preferably derived from a plant.
An oil solution prepared by dissolving the ceramides of the present invention in fatty acid triglycerides can be emulsified and used as a skin external preparation such as cosmetics. For example, an oil-in-water emulsion. Since it is an oil solution containing a high content of ceramides, a small amount is sufficient to realize an emulsion containing a necessary amount of ceramides, and a high-concentration emulsion can also be provided.
Since the oil solution of the ceramides of the present invention is stable, it is not necessary to add a large amount of a surfactant to mix the ceramides. In order to dissolve ceramides in fatty acid triglycerides, an auxiliary agent such as a surfactant is not required in addition to the phytosterol derivative, so that an oil solution that is highly safe for the human body can be provided. A highly safe substance can be selected when an emulsifier or the like to be added when a dosage form such as an emulsion is formulated.

Each component is described below.
1. Examples of the ceramides of the present invention include ceramides, ceramide derivatives, and ceramide-like substances.
Examples of ceramide include N-acyl sphingosine (ceramide), N-acyl dihydrosphingosine (dihydroceramide), N-acyl phytosphingosine (phytoceramide) and the like. The structure of the sphingosine is (2S, 3R, 4E) -2-amino-4-octadecene-1,3-diol, and the structure of dihydrosphingosine is (2S, 3R) -2-aminooctadecane-1,3-diol. The structure of phytosphingosine is (2S, 3S, 4R) -2-amino-1,3,4-octadecanetriol.
In particular, as ceramides used in the present invention, ceramide 2 (name of cosmetic raw material) classified as N-acyl dihydrosphingosine (dihydroceramide), ceramide 3 (cosmetic raw material indication) classified as N-acyl phytosphingosine (phytoceramide) Name) is preferred.
The chemical formula of ceramide 2 (name of cosmetic ingredient display) used in the present invention is (2S, 3R) -2-octadecanoylaminooctadecane-1,3-diol, which is a commercially available product (Ceramide TIC-001 manufactured by Takasago International Corporation). ) Can be used.
The chemical formula of ceramide 3 (cosmetic raw material display name) used in the present invention is 2-octadecanoylamino-1,3,4-octadecanetriol, and a commercially available product (DS-Ceramide Y3S manufactured by DOOSAN) can be used.
Examples of ceramide derivatives include sphingomyelin, cerebroside, ganglioside, sulfatide, sphingosine, acyl sphingosine and the like. Examples of acylsphingosine include tetraacetylphytosphingosine, and commercially available products (DS-TAPS manufactured by DOOSAN) can be used.
Examples of the ceramide-like substance include N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide, trihydroxypalmitamide hydroxypropyl myristyl ether, cetylhydroxyprolymphrmitamide and the like. . As the trihydroxypalmitamide hydroxypropyl myristyl ether, a commercially available product (CERAMIDE HO3 manufactured by Cederma) can be used.

N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexa of the present invention Since the decanamide oil solution is stable, a surfactant such as sorbitan monolaurate is used for the purpose of dissolving N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide. There is no need to add a large amount. In order to dissolve N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide in a fatty acid triglyceride, no auxiliary agent such as a surfactant is required in addition to the phytosterol derivative. It is possible to provide a highly safe oil solution against A highly safe substance can be selected when an emulsifier or the like to be added when a dosage form such as an emulsion is formulated.

N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide is a ceramide-like substance and has an excellent effect in improving rough skin. As this compound, a commercially available product (Sofcare Ceramide SL-E manufactured by Kao Corporation) can be used.
An effect of improving skin roughness can be obtained by blending N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide with a skin external preparation at a concentration of 0.001% by mass or more.

2. Fatty acid triglyceride Fatty acid triglyceride is a highly polar oil and can be suitably used regardless of whether it is derived from animal oil or vegetable oil or synthesized. For example, camellia oil, evening primrose oil, macadamia nut oil, olive oil, rapeseed oil, corn oil, sesame oil, wheat germ oil, glycerin trioctanoate and the like can be used. In particular, macadamia nut oil contains nearly 25% palmitooleic acid and is an oil that is close to sebum, and exhibits an excellent effect on improving rough skin when used together with a ceramide-like substance.

  In addition, it is estimated that the common oil agent squalane used for cosmetics has a low polarity, so that it has poor solubility, and is not suitable as a solvent.

3. Phytosterol derivative Phytosterol is a biologically similar component and has a high effect on improving rough skin. Phytosterol derivatives include macadamia nut fatty acid phytosteryl, phytosteryl oleate, dimer linoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimer dilinoleic acid di (isostearyl / phytosteryl), dilauroyl glutamate (octyldodecyl / phytosteryl / behenyl) ), Dilauroyl glutamate (phytosteryl / octyldodecyl), etc., and any of these may be commercially available.

4). External preparation for skin The oil solution comprising the ceramides, fatty acid triglycerides, and phytosterol derivatives of the present invention can be stably blended into the external preparation for skin. Examples of the external preparation for skin include external preparations for skin, quasi drugs, and cosmetics. Examples of the dosage form include ointments, oil solutions, and emulsion compositions (creams, emulsions, etc.).

5. Other formulation components The following components can be used in the external preparation for skin of the present invention.
In the external preparation for skin of the present invention, hydrocarbon oil-based oil components, higher alcohol-based oil components, higher fatty acid-based oil components, silicone-based oil components, and the like can be used as long as the effects of the present invention are not impaired.

  Examples of the hydrocarbon oil-based oil component include squalane, liquid paraffin, squalene, and microcrystalline wax.

  Examples of higher alcohol oil components include linear alcohols such as lauryl alcohol, stearyl alcohol, cetyl alcohol, and cetostearyl alcohol, branched chain alcohols such as octyldodecanol, monostearyl glycerin ether, lanolin alcohol, cholesterol, and phytosterol. Can be mentioned.

  Examples of the higher fatty acid oil component include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and the like.

  Examples of the silicone-based oil component include linear polysiloxanes such as dimethylpolysiloxane and methylphenylpolysiloxane, and cyclic polysiloxanes such as decamethylcyclopentasiloxane.

  The skin external preparation of the present invention includes polyhydric alcohols, moisturizers, sugars, surfactants, preservatives, sequestering agents, polymers such as water-soluble polymers, thickeners, powder components, UV absorption. Agent, ultraviolet blocking agent and the like. In addition, vitamins, skin activators, blood circulation promoters, active oxygen scavengers, anti-inflammatory agents, whitening agents, bactericides, and other cosmetic ingredients, medicinal ingredients, and physiologically active ingredients can also be included.

  Examples of the polyhydric alcohol include polyethylene glycol, dipropylene glycol, 1,3-butylene glycol, 1,2-pentanediol, propylene glycol, isoprene glycol, glycerin, diglycerin and the like.

  Examples of the humectant include xylitol, maltitol, maltose, sorbitol, glucose, fructose, sodium chondroitin sulfate, sodium hyaluronate, sodium lactate, pyrrolidone carboxylic acid, cyclodextrin and the like.

Examples of the surfactant include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants.
Examples of nonionic surfactants include polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid esters, sucrose fatty acid esters, polyoxyethylene polyoxypropylene alkyl ethers, and the like. It is done.
Examples of the anionic surfactant include fatty acid salts such as sodium laurate, higher alkyl sulfates such as sodium lauryl sulfate, alkyl ether sulfates such as POE lauryl sulfate triethanolamine, N-acyl sarcosine acid and sulfosuccinic acid. Salts, N-acylamino acid salts and the like.
Examples of the cationic surfactant include alkyltrimethylammonium salts such as stearyltrimethylammonium chloride, benzalkonium chloride, and benzethonium chloride.
Examples of amphoteric surfactants include betaine surfactants such as alkyl betaines and amide betaines.

Examples of the preservative include methyl paraben, ethyl paraben, and fequinoxyethanol.
Examples of the sequestering agent include edetates such as disodium ethylenediaminetetraacetate, edetic acid, and sodium edetate.

  Examples of water-soluble polymers or thickeners include gum arabic, gum tragacanth, galactan, guar gum, carrageenan, pectin, agar, quince seed, dextran, dextrin, pullulan, carboxymethyl starch, collagen, casein, gelatin, methylcellulose, methylhydroxy Mention may be made of propylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, sodium alginate, xanthan gum, sodium carboxymethyldextran, bentonite and the like.

  Examples of the powder component include talc, kaolin, mica, silica, zeolite, polyethylene powder, polystyrene powder, cellulose powder, inorganic white pigment, inorganic red pigment, titanium oxide coated mica, titanium oxide coated talc, and colored titanium oxide coated mica. And organic pigments such as Red No. 201 and Red No. 202.

Examples of the ultraviolet absorber include paraaminobenzoic acid, phenyl salicylate, isopropyl paramethoxycinnamate, octyl paramethoxycinnamate, and 2,4-dihydroxybenzophenone.
Examples of the ultraviolet blocking agent include titanium oxide, talc, carmine, bentonite, kaolin, and zinc oxide.

The medicinal ingredient, for example, vitamin A oil, vitamin A such as retinol, vitamin B ₂ such as riboflavin, B ₆ such as pyridoxine hydrochloride, L- ascorbic acid, L- ascorbic acid phosphoric acid ester, L- Vitamin Cs such as ascorbic acid monopalmitate, L-ascorbic acid dipalmitate, L-ascorbic acid-2-glucoside, pantothenic acids such as calcium pantothenate, vitamin Ds such as vitamin D ₂ and cholecalciferol Vitamins such as vitamin E such as α-tocopherol, tocopherol acetate, DL-α-tocopherol nicotinate; Whitening agents such as placenta extract, glutathione, and yukinoshita extract, skin activators such as royal jelly, linden extract, capsaicin, gingeron, cantalis tincture, ictamol, caffeine, tannic acid, blood circulation promoters such as γ-oryzanol, glycyrrhizic acid Derivatives, glycyrrhetinic acid derivatives, anti-inflammatory agents such as azulene, amino acids such as arginine, serine, leucine and tryptophan, maltose sucrose condensates of resident bacteria control agents, lysozyme chloride and the like. In addition, chamomile extract, parsley extract, beech extract, wine yeast extract, grapefruit extract, honeysuckle extract, rice extract, grape extract, hop extract, rice bran extract, loquat extract, buckwheat extract, yakuinin extract, assembly extract, merirot extract, birch extract, licorice extract , Peony extract, bonito extract, loofah extract, capsicum extract, lemon extract, gentian extract, perilla extract, aloe extract, rosemary extract, sage extract, thyme extract, tea extract, seaweed extract, cucumber extract, clove extract, carrot extract, Examples include various extracts such as maroni extract, hamamelis extract and mulberry extract.

<Test Example 1>
A combination of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide, an oil agent (fatty acid triglyceride, hydrocarbon) and a phytosterol derivative produces N- (2-hydroxy-3-hexa The solubility of (decyloxypropyl) -N-2-hydroxyethylhexadecanamide was evaluated.

N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide, oil agent (fatty acid triglyceride, hydrocarbon) and 6 types of phytosterol derivatives were combined to test their solubility. To do. N- (2-Hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide is not recognized as soluble alone with macadamia nut oil, and uses macadamia nut oil that is well-suited to sebum For the purpose of developing a technology for dissolving N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide, attention was paid to phytosterol derivatives as adjuvants to improve solubility. A solubility confirmation test was conducted.
(1) The content of the ceramide-like substance is 0.2% by mass with respect to the macadamia nut oil serving as a solvent, and 6 types of phytosterol derivatives are given to the solubility as 2%, 10%, and 20% with respect to the macadamia nut oil. Tested with effects. Each is shown in Table 1, Table 2, and Table 3 together with the evaluation results of the dissolved state.
(2) The effect of ceramide-like substances on the solubility of 0.02% by mass with respect to macadamia nut oil as a solvent, and 6 types of phytosterol derivatives at 2%, 10%, and 20% with respect to macadamia nut oil Was tested. Each is shown in Table 4, Table 5, and Table 6 together with the evaluation results of the dissolved state.
(3) Based on the results of the above (1) and (2), a test for confirming the upper limit of dissolution of the ceramide-like substance and the upper limit of addition of the phytosterol derivative with respect to the macadamia nut oil was confirmed by the formulation shown in Table 7.
(4) A comparative test was conducted using squalane as a solvent. Table 8 shows the formulation and evaluation of solubility.
(5) The solubilization method is as follows: 5 g of macadamia nut oil, Sofcare Ceramide SL-E (Kao Corporation) as N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide The compounding amounts shown in each table are heated and dissolved, and each phytosterol derivative is added to the compounding amounts shown in each table and further dissolved by heating. In addition, it shows in Table 9 about the physical-property value and source of the component used for the test.
(6) Evaluation is made visually by the following criteria to see if crystals are present in the solution after 3 days (room temperature standing).
○: Crystal does not precipitate and is transparent.
Δ: Crystals do not precipitate but become cloudy.
X: Crystals precipitate.

The following can be seen from the results in Table 1.
Although 0.2% by weight of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide could not be dissolved in macadamia nut oil, f-1 ~ 0.2% by mass of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide is stably dissolved by adding 2% by mass of phytosterol derivative of ~ f-6 We were able to.

The following can be seen from the results in Table 2.
By adding 10% by mass of f-2 to f-4 and f-6 phytosterol derivatives to macadamia nut oil, 0.2% by mass of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2- Hydroxyethylhexadecanamide could be dissolved stably. However, when macadamia nut oil is blended with 10% by weight of f-1 macadamia nut fatty acid phytosteryl, 0.2% by weight of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethyl Hexadecanamide could not be dissolved. When macadamia nut oil is blended with 10% by weight of f-5 dilauroyl glutamate (octyldodecyl / phytosteryl / behenyl), 0.2% by weight of N- (2-hydroxy-3-hexadecyloxypropyl)- Although N-2-hydroxyethylhexadecanamide could be dissolved and no crystals were precipitated, white turbidity occurred.

The following can be understood from the results in Table 3.
By adding 20% by mass of f-4 and f-6 phytosterol derivatives to macadamia nut oil, 0.2% by mass of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadeca Namide could be dissolved stably. However, when macadamia nut oil is blended with 20% by mass of f-1, f-2 phytosterol derivatives, 0.2% by mass of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2 -Hydroxyethyl hexadecanamide could not be dissolved. When macadamia nut oil is blended with 20% by mass of f-3 and f-5 phytosterol derivatives, 0.2% by mass of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxy Ethylhexadecanamide could be dissolved and no crystals were precipitated, but white turbidity occurred.

The following can be seen from the results in Table 4.
By blending 2% by mass of phytosterol derivatives of f-1 to f-6 with macadamia nut oil, 0.02% by mass of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadeca Namide could be dissolved stably.

The following can be understood from the results of Table 5.
By blending macadamia nut oil with 10% by mass of f-2 to f-4, f-6 phytosterol derivatives, 0.02% by mass of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2- Hydroxyethylhexadecanamide could be dissolved stably. However, when macadamia nut oil is blended with 10% by weight of f-1 macadamia nut fatty acid phytosteryl, 0.02% by weight of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethyl Hexadecanamide could not be dissolved. Compared to Table 2, N- (2-hydroxy-3-hexadecyloxypropyl) -N-2
Although the concentration of hydroxyethylhexadecanamide was 1/10, the solubility did not change. When macadamia nut oil is blended with 10% by weight of f-5 dilauroyl glutamate (octyldodecyl / phytosteryl / behenyl), 0.02% by weight of N- (2-hydroxy-3-hexadecyloxypropyl)- Although N-2-hydroxyethylhexadecanamide could be dissolved and no crystals were precipitated, white turbidity occurred.

The following can be understood from the results of Table 6.
By adding 20% by mass of f-4 and f-6 phytosterol derivatives to macadamia nut oil, 0.02% by mass of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadeca Namide could be dissolved stably. However, when macadamia nut oil is blended with 20% by mass of f-1, f-2 phytosterol derivatives, 0.02% by mass of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2 -Hydroxyethyl hexadecanamide could not be dissolved. Compared with Table 3, the concentration of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide was set to 1/10, but the solubility was not changed. When macadamia nut oil is blended with 20% by mass of f-3 and f-5 phytosterol derivatives, 0.02% by mass of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxy Ethylhexadecanamide could be dissolved and no crystals were precipitated, but white turbidity occurred.

The following can be understood from the results of Table 7.
As shown in Table 2, when 10% by mass of f-1 macadamia nut fatty acid phytosteryl was added to macadamia nut oil, 0.2% by mass of N- (2-hydroxy-3-hexadecyloxypropyl) -N Although 2-hydroxyethyl hexadecanamide could not be dissolved, when macadamia nut oil was blended with 6% by mass of f-1 macadamia nut fatty acid phytosteryl, 0.2% by mass of N- (2 -Hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide could be dissolved.

  From the results in Table 8, the ceramide derivative was not dissolved in squalane, which is a low polarity oil, and even when a phytosterol derivative was added, no improvement in dissolution was observed.

<Effects on N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethyl hexadecanamide solution>
N- (2-Hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide, a stable dissolved N- (2-hydroxy-3-hexadecyloxypropyl) -N A 2-hydroxyethyl hexadecanamide solution can be provided. It is clear that the liquid phytosterol derivative does not interfere with the dissolution of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide at room temperature, but acts as an auxiliary. I was able to. Phytosterol derivatives that are solid at room temperature, particularly macadamia nut fatty acid phytosteryl, have good solubility in the range of fatty acid triglyceride: phytosterol derivative = 50: 1 to 10: 1, and promotes ceramide precipitation above 10: 1. In particular, in the case of solid phytosterol derivatives, the solubility is not improved just because the total amount of the oil agent is increased. N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanami We can clearly show that there is a moderate ratio to stabilize the mode.
In general, to improve the rough skin improvement effect by blending N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide, a ceramide-like substance, into an external preparation for skin Needs to be blended in an amount of 0.001% by mass or more. Since the oil solution of the present invention contains a high concentration of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide, the skin external preparation is 0.5 to 5% by mass. By adding the fatty acid triglyceride, it is possible to realize a blend of 0.001% by mass or more of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide Both feeling and rough skin improvement effect can be realized.
The present invention provides a high concentration N- (2-hydroxy-3-hexadecyloxy) using fatty acid triglycerides and phytosterol derivatives as solvents without using sorbitan monolaurate and amphiphilic polymers used in the prior art. Propyl) -N-2-hydroxyethylhexadecanamide could be dissolved. Accordingly, it is possible to provide an external preparation for skin that has high safety and can be freely designed for use.

[Solubility test of ceramides]
The solubility of ceramides was evaluated by a combination of ceramides (ceramide 2, ceramide 3, tetraacetyl phytosphingosine, trihydroxypalmitamide hydroxypropyl myristyl ether), fatty acid triglycerides, and phytosterol derivatives.

  A combination of ceramides, fatty acid triglycerides and three phytosterol derivatives is tested for solubility. The ceramides are not solubilized alone with macadamia nut oil, and as an auxiliary to improve solubility for the purpose of developing technology to dissolve ceramides using macadamia nut oil that is well-suited to sebum Focusing on phytosterol derivatives, a solubility confirmation test was conducted.

The dissolution method involves heating and dissolving the compounding amounts shown in Tables 11 to 14 for ceramides in 5 g of macadamia nut oil, adding the compounding amounts shown in each table for each phytosterol derivative, and further dissolving by heating. Three types of phytosterol derivatives were used: macadamia nut fatty acid phytosteryl (f-1), phytosteryl oleate (f-2), and lauroylglutamate di (phytosteryl / octyldodecyl) (f-6). The sources of ceramides used in the test are shown in Table 10.

The evaluation of each ceramide compound is visually confirmed according to the following criteria for crystals not appearing in the solution after 3 days (room temperature standing).
○: Crystal does not precipitate and is transparent.
Δ: Crystals do not precipitate but become cloudy.
X: Crystals precipitate.

<Test Example 2>
The content of ceramide 2 was 0.02 mass% with respect to the macadamia nut oil used as a solvent, and the effect of 3 types of phytosterol derivatives on the solubility was determined with 2%, 10%, and 20% with respect to the macadamia nut oil. Table 11 shows the results of dissolution state evaluation.

The following can be seen from the results in Table 11.
It can be seen that ceramide 2 cannot be dissolved only with macadamia nut oil, and the solubility can be improved by blending phytosterol with macadamia nut oil. It can be seen that there is a difference in blending amount and solubility depending on the type of phytosterol. When the macadamia nut fatty acid phytosteryl of f-1 is blended in an amount of 2 to 10% by weight based on the macadamia nut oil, 0.02% by weight of ceramide 2 can be dissolved. It can be seen that when 20 wt% is blended, 0.02 wt% of ceramide 2 cannot be dissolved.
F-2 phytosteryl oleate and f-6 dilauroyl glutamate (phytosteryl / octyldodecyl) dissolve 0.02% by weight of ceramide 2 when blended in 2 to 20% by weight with respect to macadamia nut oil. Is done.

<Test Example 3>
The content of ceramide 3 was 0.02% by mass with respect to the macadamia nut oil used as a solvent, and three types of phytosterol derivatives were tested with 2%, 10%, and 20% with respect to the macadamia nut oil to test the influence on the solubility. Table 12 shows the results of evaluation of the dissolved state.

The following can be understood from the results of Table 12.
It can be seen that ceramide 3 cannot be dissolved only with macadamia nut oil, and the solubility can be improved by blending phytosterol with macadamia nut oil. It can be seen that there is a difference in blending amount and solubility depending on the type of phytosterol. When the macadamia nut fatty acid phytosteryl of f-1 and phytosteryl oleate of f-2 are blended in an amount of 2 to 10% by weight based on the macadamia nut oil, 0.02% by weight of ceramide 2 can be dissolved. It can be seen that when 20 wt% is blended, 0.02 wt% of ceramide 2 cannot be dissolved.
The f-6 dilauroyl glutamate (phytosteryl / octyldodecyl) can dissolve 0.02% by weight of ceramide 2 when blended in 2 to 20% by weight with respect to macadamia nut oil.

<Test Example 4>
Tested the effect of tetraacetylphytosphingosine content on the solubility of 0.02% by mass with respect to macadamia nut oil as a solvent, and 3 types of phytosterol derivatives as 2%, 10% and 20% with respect to macadamia nut oil did. Table 13 shows the results of evaluation of the dissolved state.

The following can be seen from the results in Table 13.
It can be seen that tetraacetylphytosphingosine cannot be dissolved only with macadamia nut oil, and the solubility can be improved by blending phytosterol with macadamia nut oil. It can be seen that there is a difference in blending amount and solubility depending on the type of phytosterol.
The f-1 macadamia nut fatty acid phytosteryl can dissolve 0.02% by weight of ceramide 2 when blended with 2% by weight of the macadamia nut oil. It can be seen that when 10 wt% and 20 wt% are blended, 0.02 wt% of ceramide 2 cannot be dissolved.
The f-2 phytosteryl oleate can dissolve 0.02% by weight of ceramide 2 when blended with 2 to 10% by weight of macadamia nut oil. It can be seen that when 20 wt% is blended, 0.02 wt% of ceramide 2 cannot be dissolved.
The f-6 dilauroyl glutamate (phytosteryl / octyldodecyl) can dissolve 0.02% by weight of ceramide 2 when blended in 2 to 20% by weight with respect to macadamia nut oil.

<Test Example 5>
The content of trihydroxypalmitamide hydroxypropyl myristyl ether is 0.02% by mass with respect to macadamia nut oil as a solvent, and three phytosterol derivatives are soluble at 2%, 10%, and 20% with respect to macadamia nut oil. The effects on the test were tested. Table 14 shows the results of the dissolution state evaluation.

The following can be seen from the results in Table 14.
It can be seen that trihydroxypalmitamide hydroxypropyl myristyl ether cannot be dissolved only with macadamia nut oil, and the solubility can be improved by blending phytosterol with macadamia nut oil. It can be seen that there is a difference in blending amount and solubility depending on the type of phytosterol. When the macadamia nut fatty acid phytosteryl of f-1 is blended in an amount of 2 to 10% by weight based on the macadamia nut oil, 0.02% by weight of ceramide 2 can be dissolved. It can be seen that when 20 wt% is blended, 0.02 wt% of ceramide 2 cannot be dissolved.
F-2 phytosteryl oleate and f-6 dilauroyl glutamate (phytosteryl / octyldodecyl) dissolve 0.02% by weight of ceramide 2 when blended in 2 to 20% by weight with respect to macadamia nut oil. Is done.

Formulation Example 1 Cloudy lotion Ingredients Amount (% by mass)
1. N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide 0.001
2.Lauroyl glutamate di (phytosteryl / octyldodecyl) 0.05
3.Macadamia nut oil 0.5
4.Glycerin 5
5.1,3-Butylene glycol 6
6.1,2-Pentanediol 2
7.Ethylhexylglycerin 1
8.Carboxyvinyl polymer 0.05
9.Potassium hydroxide 0.02
10.Xanthan gum 0.01
11.Trimethylglycine 0.1
12. Butosugar 0.3
13. Hydrogenated lecithin 2.0
14.Purified water residue

Preparation method 1) 1 is dissolved in 2 and 3 at 85 ° C or higher.
2) 4-8 and 10-13 are dissolved by heating to 85 ° C, and 1) is added.
3) Add 9 and stir to dissolve.
4) It cooled to 30 degreeC and obtained the cloudy lotion.
The oil content in the obtained emulsified cosmetic is about 0.5% by mass, and N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanami is achieved while realizing a refreshing feeling of use. 0.001% by mass of the dough, and excellent in rough skin improvement effect.

Formulation Example 2 Emulsion Ingredient Amount (% by mass)
1. Purified water Residual 2. Carboxyvinyl polymer 0.05
3. Glycerin 5
4). Raffinose 2
5. Alanylglutamine 0.1
6). Creatine 0.1
7). Hyaluronic acid Na 0.001
8). Dipropylene glycol 2
9. Hydrogenated lecithin 0.2
10. 1,2-Pentanediol 2
11. PEG-60 hydrogenated castor oil 0.7
12 Arlatone 2121 0.4
13. Dimethicone 5
14 Squalane 2
15. Jojoba oil 2
16. Macadamia nut oil 0.5
17. Macadamia nut fatty acid phytosteryl 0.01
18. N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide 0.001
19.1,3-Butylene glycol 4
20. SIMULGEL NS 1
21. Potassium hydroxide 0.006
* Arlatone 2121 is a premix raw material of 92.5% sorbitan stearate and 7.5% coconut fatty acid sucrose manufactured by Unikema Japan * SIMULGEL NS is manufactured by SEPPIC
(Hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer 37.5%, squalane 25.5%, polysorbate 60 5.5%, water 30.0%, sorbitan isostearate 1.5% premix raw material

Preparation method 1) 2 is dissolved in 1.
2) Confirm the dissolution of 1), add 3-10, warm to 85 ° C and dissolve, then cool to 50 ° C.
3) Heat 11 to 15 at 85 ° C and dissolve, and cool to 50 ° C.
4) Heat to 16-18 and dissolve, add to 3) and stir.
5) Gradually add 2) to 4), emulsify for 5 minutes at 3000 rpm homomixer, and then add 21.
6) Add 19 and 20 to 5) and mix.
7) 6) was cooled to 30 ° C. to obtain an emulsion.

Formulation Example 3 Gel serum liquid Ingredients (Mass%)
1. Macadamia nut oil 2.5
2. Dimerlinoleic acid di (isostearyl / phytosteryl) 0.5
3. Trihydroxypartamide hydroxypropyl myristyl 0.001
4). Wed 76.739
5. Methylparaben 0.15
6). BG 7
7). Glycerin 5
8). Ethanol 5
9. Dimethicone 2
10. Licorice root extract 0.01
11. Xanthan gum 0.3
12 Polysorbate 60 0.2
13. Carboxyvinyl polymer 0.45
14 Arginine 0.1
15. Silica 0.05

Preparation method 1) 3 is heated and dissolved in 1 and 2.
2) 4-13 and 15 are heated and dissolved at 85 ° C., and 1) is added.
3) Gradually add 14 to 2) and stir for 5 minutes with a homomixer of 3000 rpm.
4) Cooled to 30 ° C. to obtain a gel serum.

Formulation Example 4 Cream Ingredient Amount (% by mass)
1. Hibiswako 103 0.14
2. Methylparaben 0.15
3. L-serine 0.01
4). Dipotassium glycyrrhizinate 0.05
5. Polysorbate 60 0.5
6). Glycerin 4
7. 1,3-Butylene glycol 7
8). Macadamia nut oil 5
9. Lauroyl glutamate di (phytosteryl / octyldodecyl) 0.5
10. Ceramide 2 0.001
11. Squalane 10
12 Dimethicone (50cs) 0.5
13. Cholesteryl hydroxystearate 1
14 Behenyl alcohol 0.5
15. Stearic acid 1
16. Cetyl palmitate 1.5
17. Tocopherol 0.03
18. Retinol palmitate 0.01
19. Sorbitan stearate 1
20. Hyaluronic acid Na 0.001
21. Potassium hydroxide 0.065
22. Purified water 67.043

Preparation method 1) Add 1 to 7 to 22, and dissolve by heating at 85 ° C.
2) Warm-dissolve 10 in 8,9.
3) Heat 11 to 19 at 85 ° C. and dissolve, then add 2).
4) Add 1) to 3) gradually, emulsify at 3000 rpm for 5 minutes, and then add 21.
5) Cool to 40 ° C. and add 20.
6) The solution was further cooled to 30 ° C. to obtain a cream.

Claims (3)

Ceramide consisting of macadamia nut oil and ceramide 2, ceramide 3, or tetraacetylphytosphingosine, N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide, trihydroxypalmitamide hydroxy Any one ceramide selected from ceramide-like substances consisting of propyl myristyl ether;
Dimerlinoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimerlinoleic acid di (isostearyl / phytosteryl), lauroylglutamate di (octyldodecyl / phytosteryl / behenyl), lauroylglutamate di (phytosteryl / octyldodecyl) Containing one or more phytosterol derivatives selected from
The oil solution whose compounding ratio of macadamia nut oil , ceramides, and a phytosterol derivative is 100: 0.02-0.2: 1-20.   The oil solution according to claim 1, which does not contain sorbitan monolaurate or an amphiphilic polymer. An external preparation containing 0.5 to 5% by mass of macadamia nut oil, 0.001% by mass or more of ceramides and a phytosterol derivative,
Ceramide whose ceramide is ceramide 2 or ceramide 3, or tetraacetylphytosphingosine, N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide, trihydroxypalmitamide hydroxy Any one selected from ceramide-like substances consisting of propyl myristyl ether,
Phytosterol derivatives include dimer dilinoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimer dilinoleic acid di (isostearyl / phytosteryl), lauroyl glutamate di (octyldodecyl / phytosteryl / behenyl), lauroyl glutamate di (phytosteryl / One or more selected from octyldodecyl),
Furthermore, the skin external preparation characterized by the compounding ratio of macadamia nut oil , ceramides and phytosterol derivative in the external preparation for skin being 100: 0.02 to 0.2: 1 to 20.