JP5279209B2 - Topical skin preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation containing urea in high concentration, excellent in feeling in use and moisturizing effect and also excellent in stability and safety. <P>SOLUTION: The skin care preparation contains urea in high concentration and retinol. This skin care preparation has the above-mentioned advantages, thus being fully hopeful of the pharmacological effects of the active ingredients therein. <P>COPYRIGHT: (C)2008,JPO&amp;INPIT

Description

The present invention relates to a skin external preparation excellent in feeling of use containing urea and retinol or a derivative thereof. Furthermore, this invention relates to the skin external preparation excellent in moisture retention, formulation stability, and safety.

Urea is a component widely used in external compositions as a moisturizer, penetration aid, rough skin improving agent, emollient, cell activator, and the like. However, a composition containing urea at a high concentration in order to give high moisturizing power and emollient power is problematic in that urea tends to precipitate and impairs the original pharmacological action of urea and the feeling during use. For this reason, studies have been made for a long time to suppress urea precipitation. For example, urea is 0.5 to 30% by weight and polyhydric alcohol is 25 to 80% by weight.
In a transparent gel preparation containing 20% by weight, 20 to 70% by weight of water, and other two components, there is a description that a problem of crystal precipitation occurs when urea becomes 30% by weight or more (Patent Document 1: Japanese Patent Laid-Open No. 63-63). No. 166825)
It is suggested that precipitation can be prevented if urea is 30% by weight or less.
On the other hand, retinol or its derivative is a vitamin known to be involved in the maintenance of biological functions such as vision and hearing, and the regeneration function of normal epithelial tissues such as skin and mucous membranes by promoting metabolism, Cosmetics for the prevention of skin aging such as anti-wrinkles as a topical medicine for keratinized skin diseases (such as ichthyosis vulgaris, pore lichen, simple rash) Widely used as a fee. However, the effect of combining with a high concentration of urea is not known.
Furthermore, since urea may irritate the skin or it may undergo hydrolysis to produce an ammonia odor, it is also desired to improve safety and formulation stability.

This invention makes it a subject to provide the skin external preparation excellent in the usability | use_condition containing high concentration urea. Furthermore, this invention makes it a subject to provide the skin external preparation excellent in moisture retention, formulation stability, and safety | security.

As a result of intensive studies to achieve the above object, the present inventors have found that the use feeling is improved when retinol or a derivative thereof is added to a composition containing a high concentration of urea. In addition, the inventors have found that it is excellent in moisture retention, formulation stability and safety, and completed the present invention.
That is, this invention is a skin external preparation listed to following (1)-(5).
(1) A skin external preparation containing 10 to 25% by weight of urea and retinol or a derivative thereof.
(2) The skin external preparation according to (1), wherein the retinol derivative is selected from the group consisting of a retinol fatty acid ester, a retinol oxide, and a retinol oxide ester.
(3) The skin external preparation according to (1), wherein the retinol derivative is one or more selected from the group consisting of retinol acetate, retinol palmitate, and δ-retinoic acid tocopherol.
(4) The external preparation for skin according to any one of (1) to (3), further containing tocopherol or a derivative thereof.
(5) The skin external preparation according to any one of (1) to (4), further comprising a chelating agent, an antioxidant, an anti-inflammatory agent, a moisturizing agent, a whitening agent, a cell activator and an anti-wrinkle agent.
The present invention also includes the following methods.
(6) A method for suppressing urea precipitation by containing urea and retinol or a derivative thereof.
(7) The method according to (6), further comprising tocopherol or a derivative thereof.
(8) A method for stabilizing retinol or a derivative thereof by containing urea and retinol or a derivative thereof.

This invention can provide the skin external preparation excellent in the usability | use_condition by containing a high concentration urea and retinol or its derivative (s). Furthermore, this invention can improve moisture retention by containing a high concentration urea and retinol or its derivative (s).

BEST MODE FOR CARRYING OUT THE INVENTION

The external preparation for skin of the present invention is characterized by containing 10 to 25% by weight of urea and retinol or a derivative thereof.

The amount of urea used in the present invention is not particularly limited as long as the effects of the present invention are exhibited, but as a whole external preparation for skin, 10 to 25% by weight, preferably 10 to 20% by weight, particularly preferably 15 to 20% by weight. %
If it is good.

In the present invention, retinol derivatives include retinol acetate, retinol propionate, retinol butyrate, retinol octylate, retinol laurate, retinol palmitate, retinol stearate, retinol myristate, retinol oleate, retinol linolenate, retinol linoleate, etc. Retinol fatty acid esters, retinal, retinoic acid such as retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, tocopherol retinoic acid (tocopherol may have any structure of α, β, γ, δ ) And the like, and retinoic acid may be a salt (for example, sodium retinoic acid). Preferred are retinol acetate, retinol palmitate, and tocopherol δ-retinoate.

In addition, retinol or a derivative thereof used in the present invention is a natural oil extracted and purified from animals (
Liver oil, etc.) or chemically synthesized. It may also be a vitamin A oil described in the Japanese Pharmacopoeia (including 30,000 vitamin A units (IU) or more per gram).

The amount of retinol or a derivative thereof used in the present invention is not particularly limited as long as the effect of the present invention is achieved, but as a whole external preparation for skin, 0.001 to 1% by weight, preferably 0.01 to 0.5% by weight.
If it is good.

Further, in the external preparation for skin of the present invention, the ratio of urea to retinol or a derivative thereof is not particularly limited as long as the effect of the present invention is exerted, but the total amount of retinol or a derivative thereof is 1
Urea is usually 1 to 300 parts by weight, preferably 10 to 200 parts by weight, particularly preferably 2 parts by weight.
0 to 100 parts by weight.

To the skin external preparation of the present invention, tocopherol or a derivative thereof can be blended in order to further improve the feeling of use and moisture retention and to stabilize the preparation.
In the present invention, tocopherol means α-tocopherol, β-tocopherol, γ-
Either tocopherol or δ-tocopherol may be used, and α-tocopherol and δ-tocopherol are preferred. These tocopherols may be either d-form or dl-form.
In addition, the tocopherol derivative includes tocopherol organic acid esters such as tocopherol acetate, tocopherol succinate, tocopherol nicotinate and tocopherol linolenate, and may be a salt when the organic acid is not a monocarboxylic acid (for example, Tocopherol calcium succinate), preferably tocopherol acetate.
These tocopherol derivatives may be either d-form or dl-form.

The blending amount of tocopherol or a derivative thereof used in the present invention is not particularly limited as long as the effects of the present invention are obtained, but 0.001 to 5% by weight, preferably 0.01 to 3% by weight, particularly preferably 0.5% as a whole for the external preparation for skin. It should be ~ 2% by weight.

The external preparation for skin of the present invention can be blended with one or more chelating agents or antioxidants in order to stabilize the preparation. Each of these components is not particularly limited as long as it is conventionally used as a component of a skin external preparation in the pharmaceutical, quasi-drug, or cosmetic field, and used in the future. Can be used.

Examples of the chelating agent include ethylenediaminetetraacetic acid (edetic acid), ethylenediaminetetraacetic acid salt (sodium salt (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.)
, Potassium salts, etc.), phytic acid, gluconic acid, polyphosphoric acid, metaphosphoric acid, and the like. Preferred are edetic acid, sodium edetate, potassium edetate, and phytic acid.

These chelating agents can be used singly or in combination of two or more. The proportion of the chelating agent blended in the external preparation for skin of the present invention is usually 0.0003 to 20 for the entire external preparation for skin as the total amount of the chelating agent.
% By weight, preferably 0.01 to 10% by weight, particularly preferably 0.05 to 5% by weight.

Antioxidants include butylhydroxyanisole, dibutylhydroxytoluene, sodium bisulfite, erythorbic acid and its salts, glutathione, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase, thioredoxin, taurine, thiotaurine, hypotaurine, etc. Can be mentioned. Preferred are butylhydroxyanisole and dibutylhydroxytoluene.

When an antioxidant component is used, it is not particularly limited as long as the effects of the present invention are exhibited, and can be appropriately selected and used in consideration of the feeling of use and effects on the skin. 0.00
It is 001-10 weight%, Preferably it is 0.0001-5 weight%, More preferably, it is 0.001-5 weight%.

In order to add other useful effects to the external preparation for skin of the present invention, various components such as an anti-inflammatory agent, a moisturizing agent, a whitening agent, a cell activator, an anti-wrinkle agent, etc. are used alone or in combination. Can be blended. Preferably, it is one or more components of an anti-inflammatory agent or a cell activator. Each of these components is not particularly limited as long as it is conventionally used as a component of a skin external preparation in the pharmaceutical, quasi-drug, or cosmetic field, and used in the future. Can be used.

Anti-inflammatory agents include indomethacin, methyl salicylate, allantoin, allantoin β-glycyrrhetin, allantochlorohydroxyaluminum, glycyrrhizic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, glycyrrhetinic acid, stearyl glycyrrhetinate, pyridoxine glycyrrhetinate, zinc oxide, azulene Examples include sulfonic acid, guaiazulene sulfonic acid, pyridoxine hydrochloride, lysozyme chloride, menthol, camphor and the like. Preferably, allantoin, dipotassium glycyrrhizinate,
Monoammonium glycyrrhizinate, guaiazulene sulfonic acid, and menthol.

When the anti-inflammatory agent is used, the ratio to be blended in the external preparation for skin of the present invention is not particularly limited as long as the effects of the present invention are exhibited, and should be appropriately selected and used in consideration of use feeling and effects on the skin. However, it is usually 0.0003 to 10% by weight, preferably 0.01 to 5% by weight, based on the whole external preparation for skin.

As the humectant, amino acids such as alanine, serine, leucine, isoleucine, threonine, glycine, proline, hydroxyproline, aspartic acid, arginine, and theanine and derivatives thereof; ethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin, Polyhydric alcohols such as diethylene glycol, triethylene glycol, tetraethylene glycol, dipropylene glycol, diglycerin, polyethylene glycol; ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether , Diethylene glycol monopropyl ether, diethylene glycol Glycol ethers such as nobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, dipropylene glycol monopropyl ether; sugar alcohols such as mannitol, sorbitol, erythritol, xylitol, trehalose; lecithin, hydrogen Phospholipids such as added lecithin; Mucopolysaccharides such as sodium hyaluronate, sodium acetyl hyaluronate, heparin-like substances, chondroitin sulfate sodium; polymer compounds such as collagen, elastin, keratin, chitin, chitosan, gelatin, polyglutamic acid; sodium lactate N, such as sodium pyrrolidonecarboxylate
MF-derived ingredients: chamomile extract, aloe extract, aloe vera extract, chammellus extract,
In addition to plant extract extracts such as rosemary extract, thyme extract, tea extract, perilla extract, and the like. Preferably, glycine, glycerin, 1,3-butylene glycol,
Dipropylene glycol, diglycerin, diethylene glycol monoethyl ether, sodium hyaluronate, sodium acetyl hyaluronate, sodium pyrrolidone carboxylate, and polyglutamic acid.

When a moisturizer is used, it is not particularly limited as long as the effects of the present invention are exhibited, and can be appropriately selected and used in consideration of the feeling of use and effects on the skin. ~
50% by weight, preferably 0.1 to 10% by weight, more preferably 0.5 to 5% by weight.

Whitening agents include hydroquinone, quinones such as arbutin, α-hydroxy acids such as glycolic acid, citric acid, malic acid, tartaric acid, and lactic acid, ascorbic acid, ascorbyl tetraisopalmitate, ascorbyl stearate, ascorbyl palmitate, phosphorus Vitamin C or derivatives thereof such as acid L-ascorbyl magnesium and ascorbic acid glucoside, Iris (iris), almond, aloe, ginkgo, oolong tea, ages, ogon, oulen, hypericum, licorice, seaweed, cuckoo, chamomile, licorice, gardenia, Kujin, wheat, rice, rice haiga, rice bran, perilla, peony, senkyu, sakuhakuhi, soybeans, tea, terminaria, touki, shinkinka, hamamelis,
Safflower, Buttonpi, Yokuinin, Toki, Enoki, Oyster (Diospyros kak)
i), components derived from plants such as clove, extract and essential oil, placenta, cysteine, ellagic acid, kojic acid, phytic acid, lucinol, oryzanol and the like. Preferred examples include hydroquinone, arbutin, lactic acid, ascorbic acid, ascorbyl tetraisopalmitate, Iris extract, terminaria extract, and cysteine. These whitening agents may be used alone or in combination of two or more.

When using the above-mentioned whitening agent, the ratio to be blended in the external preparation for skin of the present invention is not particularly limited as long as the effects of the present invention are exhibited, and may be appropriately selected and used in consideration of use feeling and effects on the skin. However, it is usually 0.0003 to 20% by weight, preferably 0.01 to 10% by weight, based on the whole external preparation for skin.
Particularly preferably, it may be 0.05 to 5% by weight.

Cell activators include amino acids such as γ-aminobutyric acid and ε-aminocaproic acid, γ-oryzanol, dibenzoylthiamine, dibenzoylthiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl Hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, Vitamin B1 such as thiamine triphosphate monophosphate, riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-phosphate Sodium Le, vitamin B2 such as riboflavin tetra nicotinate, pyridoxine hydrochloride, acetic pyridoxine, hydrochloride pyridoxal,
Vitamin B6 pantothenic acid such as 5′-phosphate pyridoxal phosphate, pyridoxamine hydrochloride, pantothenic acid calcium, pantothenyl alcohol (panthenol), D-pantesign,
Vitamins such as pantothenic acids such as D-pantethine, coenzyme A, pantothenyl ethyl ether and the like can be mentioned. Preferred are amino acids such as γ-aminobutyric acid and ε-aminocaproic acid, and vitamins such as pantothenic acids.

When using the above-mentioned cell activator, it is not particularly limited as long as the effects of the present invention are achieved, and can be appropriately selected and used in consideration of the feeling of use and effects on the skin, but for the entire skin external preparation, Normal
It is 0.0003-10 weight%, More preferably, it is 0.01-5 weight%.

Examples of the anti-wrinkle agent include coenzyme Q10, kinetin, glycolic acid, collagen, sodium hyaluronate, sodium acetyl hyaluronate, aloe extract, seaweed extract, maroonier extract, rosemary extract, cornflower extract, preferably coenzyme Q10, It is kinetin, sodium hyaluronate, sodium acetyl hyaluronate, rosemary extract.

The compounding amount of the anti-wrinkle agent used in the present invention is not particularly limited, but can be appropriately selected and used in consideration of the feeling of use and effects on the skin. As a whole, the external preparation for skin is usually 0.0001-30% by weight
The content may be 0.001 to 25% by weight, more preferably 0.01 to 20% by weight, and particularly preferably 1 to 20% by weight.

The method for preparing the external preparation for skin of the present invention is not particularly limited, and can be prepared by a conventional method by appropriately selecting and blending various components necessary for preparing an ordinary external preparation for skin. Moreover, the application amount and usage of the external preparation for skin of the present invention to the outer skin are not particularly limited, and it can be used usually by applying an appropriate amount to the outer skin such as skin several times a day.

The external preparation for skin of the present invention can be prepared in various forms. For example, ointments, liquids (
Examples include oils, lotions, emulsions, and aerosols, gels (including liquid crystals, microemulsions, and liposomes), creams, and ointments, gels (liquid crystals, microemulsions, and liposomes). It is useful when applied to creams.
In addition, an oil-in-water type is preferable from the viewpoint of feeling of use (stickiness, spread, moist feeling, etc.).

As an application of the external preparation for skin of the present invention, it contains urea in a high concentration, so that it treats keratosis such as elbows, knees, heels and ankles, psoriasis of the elderly, and shark skin. Pharmaceuticals such as keratin softener, rough hands, rough skin, rough lips, hot flashes after sunburn, wrinkles and sagging,
Prepares the skin, smoothes the lips, keeps the skin and lips healthy, moisturizes the skin and lips, protects the skin and lips, prevents the skin from drying, wrinkles, cracks, scratches and rashes, whitening, etc. Non-pharmaceuticals used in the field, cosmetics used for moisturizing, keratin softening, etc. can be exemplified as suitable applications, but not particularly limited thereto.

The external preparation for skin of the present invention does not impair quality such as storage stability and viscosity, and within the quantitative and qualitative range that does not impair the effects of the present invention, as necessary, in the pharmaceutical, quasi-drug or cosmetic field. Ingredients commonly used in the formulation, such as bases, surfactants, thickeners, preservatives, pH adjusters, stabilizers, irritation reducers, preservatives, colorants, dispersants, fragrances, etc. can do. In addition, these components can be mix | blended individually by 1 type or in combination of 2 or more types.

Base: Liquid paraffin, gelled hydrocarbon, ozokerite, ceresin, petrolatum, hard fat, microcrystalline wax and other hydrocarbons, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, isostearic acid, oleic acid, linol Fatty acids such as acids, trifatty acid glycerides such as glyceryl tri-2-ethylhexanoate (trioctanoin), lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, isostearyl alcohol, 2-octyldodecanol, behenyl alcohol, 2-
Higher alcohols such as hexyldecanol, highly polymerized methylpolysiloxane, dimethylpolysiloxane, dimethylsiloxane / methyl (polyoxyethylene) siloxane / methyl (polyoxypropylene) siloxane copolymer, dimethylsiloxane / methyl (polyoxyethylene) siloxane copolymer Polymer, dimethylsiloxane / methyl (polyoxypropylene) siloxane copolymer, polyoxyethylene / methylpolysiloxane copolymer, poly (oxyethylene / oxypropylene) / methylpolysiloxane copolymer, dimethylsiloxane /
Methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, alkyl acrylate copolymer methylpolysiloxane ester, crosslinked methylpolysiloxane, crosslinked methylphenylpolysiloxane, crosslinked polyether-modified silicone, Crosslinked alkyl polyether-modified silicones, polymerized silicones such as crosslinked alkyl-modified silicones, ethylene glycol monoacetate, ethylene glycol diacetate, triethylene glycol diacetate, hexylene glycol diacetate, and 2-methyl- Glycol acetate such as 2-propene-1,1-diol diacetate, triethylene glycol divalerate, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, 2,2,4- Trimethyl-1,3-pentane Glycol esters such as diisobutyrate, ethylene glycol diacrylate, diethylene glycol diacrylate, propylene glycol monoacrylate, 2,2-dimethyl-trimethylene glycol diacrylate, and 1,3-butylene glycol diacrylate Glycol dinitrates such as glycol acrylate, ethylene glycol dinitrate, diethylene glycol dinitrate, triethylene glycol dinitrate, and propylene glycol dinitrate,
2 '-[1,4-phenylenedioxy] diethanol, dioxane, butylene glycol adipic acid polyester, etc. Liquid paraffin, petrolatum, cetanol, stearyl alcohol, and dimethylpolysiloxane are preferred.

Surfactants: Sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate Glyceryl fatty acids such as glyceryl monostearate and glyceryl monostearate malic acid, polyglyceryl fatty acids such as polyglyceryl monoisostearate and polyglyceryl diisostearate, propylene glycol fatty acid esters such as propylene glycol monostearate, polyoxyethylene cured Castor oil 40,
Hardened castor oil derivatives such as polyoxyethylene hardened castor oil 50, polyoxyethylene hardened castor oil 60, polyoxyethylene hardened castor oil 80, polyoxyethylene monolaurate (2
Polyoxyethylene sorbitan fatty acid esters such as 0) sorbitan (polysorbate 20), polyoxyethylene monostearate (20) sorbitan (polysorbate 60), polyoxyethylene monooleate (20) sorbitan (polysorbate 80), polyoxyethylene Mono coconut oil fatty acid glyceryl, glycerin alkyl ether, alkyl glucoside, polyoxyethylene cetyl ether, stearylamine, oleylamine and the like. Preferred are sorbitan monostearate, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, and polysorbate 60.

Thickener: Guar gum, locust bean gum, carrageenan, xanthan gum, dextran, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium alginate, propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone , Polyvinyl methyl ether, carboxyvinyl polymer, alkyl methacrylate copolymer, sodium polyacrylate, polyethylene glycol, bentonite, dextrin fatty acid ester, pectin and the like. Preferred are polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, and alkyl methacrylate methacrylate copolymer.

Preservatives: Benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, benzyl paraoxybenzoate, paraoxybenzoic acid Methyl, phenoxyethanol, 1,2-hexanediol and the like.

pH adjusters: inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid, etc.), organic acids (lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, sodium succinate, oxalic acid, gluconic acid, Fumaric acid, propionic acid, acetic acid, aspartic acid, epsilon-aminocaproic acid, glutamic acid, aminoethylsulfonic acid, etc.), gluconolactone, ammonium acetate, inorganic base (sodium bicarbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, Calcium hydroxide, magnesium hydroxide, etc.), organic bases (monoethanolamine,
Triethanolamine, diisopropanolamine, triisopropanolamine, lysine, etc.).

These components can be used alone or in combination of two or more. Moreover, those compounding amounts are not particularly limited as long as the effects of the present invention are obtained, but can be suitably selected and used as long as the upper limit compounding amount allowed by the Pharmaceutical Affairs Law is desirable. Specifically, it can be prepared according to the purpose from the range of usually 0.001 to 20 parts by weight, preferably 0.001 to 10 parts by weight, more preferably 0.001 to 5 parts by weight per 100 parts by weight of the external preparation for skin.

Furthermore, the present invention includes a method for suppressing urea precipitation. In the method of the present invention, urea precipitation suppression can be achieved by coexisting urea and retinol or a derivative thereof. Further, it is more preferable that tocopherol or a derivative thereof coexists.
In the method of the present invention, urea, retinol or a derivative thereof, and tocopherol or a derivative thereof are the same as those used in the external preparation for skin. The blending amount of urea, retinol or a derivative thereof, tocopherol or a derivative thereof is not particularly limited as long as the effect of the present invention is achieved, but urea is usually 1 to 30% by weight, preferably 3 to 25% by weight, more preferably 5
-25% by weight, particularly preferably 10-20% by weight, with retinol or its derivatives usually being 0.
It is 001 to 1% by weight, preferably 0.01 to 0.5% by weight, and tocopherol or a derivative thereof is usually 0.001 to 5% by weight, preferably 0.01 to 3% by weight, particularly preferably 0.5 to 2% by weight.

Furthermore, this invention also includes the stabilization method of retinol or its derivative (s). In the method of the present invention, stabilization of retinol or a derivative thereof can be achieved by coexisting urea and retinol or a derivative thereof. Further, it is more preferable that tocopherol or a derivative thereof coexists.
In the method of the present invention, urea, retinol or a derivative thereof, and tocopherol or a derivative thereof are the same as those used in the external preparation for skin. The blending amount of urea, retinol or a derivative thereof, tocopherol or a derivative thereof is not particularly limited as long as the effect of the present invention is achieved, but urea is usually 1 to 30% by weight, preferably 3 to 25% by weight, more preferably 5 -25% by weight, particularly preferably 10-20% by weight, retinol or a derivative thereof is usually 0.001-1% by weight, preferably 0.01-0.5% by weight, tocopherol or a derivative thereof is usually 0.001-5% by weight, Preferably it is 0.01 to 3 weight%, Most preferably, it is 0.5 to 2 weight%.

EXAMPLES The present invention will be specifically described below with reference to examples, but these examples do not limit the scope of the present invention. In addition, especially a compounding quantity does not have a unit description, all represent weight%.

Test example 1 Usability test
In accordance with the formulation shown in Table 1, the purified water and urea are combined and dissolved in water at 70 ° C, and the oil phase in which all other components are heated and dissolved at 70 ° C is mixed with stirring and cooled to room temperature. Each of the preparations (cream preparations) prepared was evaluated by 5 females in their 30s based on the following criteria for use feeling when applying the preparations, and the average score was determined as follows.
Evaluation criteria 5 points: Feeling that the skin surface is not rough and moisturizing, 4 points: Feeling that the skin surface is not rough and dry, 3 points: Although the skin surface is not rough, especially changes in feel are felt None, 2 points: Feel that the skin surface is slightly rough, 1 point: Feel that the skin surface is rough Judgment criteria A: 4.5 or more, ○: 3.5 to 4.4, Δ: 2.5 to 3.4, ×: 2.4 or less The results are shown in Table 1.

In Comparative Example 1, since the amount of urea was 10%, the degree of roughness was lower than that in Comparative Example 2, but significant improvements were observed in Examples 1 to 3. On the other hand, in Comparative Example 2, all responded “Roughness”, but in Example 4, the roughness was considerably reduced and Examples 5 and 6 were added tocopherol acetate.
Then, the usability improved further.
As described above, the present invention is an external preparation for skin having an excellent usability and is particularly useful because it can sufficiently expect the pharmacological effect of the active ingredient because it suppresses precipitation of urea and the like.

Test Example 2 Moisturizing test
In an environment set at a temperature of 23 ± 2 ° C and a humidity of 55 ± 15%, Hos: HR-1 male hairless mice (4
The electrical conductivity (μs) of the dorsal skin surface of the weekly skin, 8 per group)
N-200EX, manufactured by IBS Co., Ltd.) (normal value).
Next, the absorbent cotton containing the acetone: ether = 1: 1 mixed solution was held for 60 seconds, and after 5 seconds, the absorbent cotton containing distilled water was held for 60 seconds. This treatment was carried out 3 times in 2 days with an interval of 5 hours or more to produce dry skin mice in which rough skin was artificially induced. To this dry skin mouse, each external preparation for skin described in Table 2 (prepared in the same manner as in Table 1: cream), 50 μL per time, at the start of the test (0 hour), after about 3 hours, after about 6 hours, The coating was applied after about 24 hours, about 27 hours, and about 30 hours. The electrical conductivity on the dry skin of the mice was measured before applying the skin external preparation (initial value), and 24 hours and 48 hours after the start of the test. In addition, the measurement of the electrical conductivity 24 hours after the start of the test was performed before the application of the skin external preparation 24 hours after the start of the test. Moreover, the electrical conductivity was similarly measured for the non-coated group as Comparative Example 6.
The results are shown in Table 2.

The moisturizing action of urea is not persistent, and Comparative Example 3 has the same effect as Comparative Example 5 after 24 and 48 hours, and the water content is increased only by adding a retinol derivative from Comparative Examples 4 and 5. It was confirmed not to. On the other hand, Example 6 was found to retain a much higher keratin water content than Comparative Examples 3 and 4.
Moreover, the same effect as Table 2 was seen also about the formulation which remove | excluded tocopherol acetate from the prescription of Table 2, However, Table 2 containing tocopherol acetate has a higher value of keratin water content as a whole. Example 6 showed the highest keratin water content.

Test Example 3 Stability test
For Examples 3 and 6 and Comparative Example 4 listed in Tables 1 and 2, after storage at 40 ° C. for 6 months, the stability of urea of the examples was evaluated by the following methods (1) and (2). Moreover, the residual amount of retinol palmitate was measured according to the Japanese Pharmacopoeia.
(1) 0.5 g of each Example was taken and spread thinly and uniformly on a flat glass plate, and precipitation of urea was visually confirmed.
(2) 1.0 g of each Example was taken and the presence or absence of ammonia odor was evaluated by sensory evaluation.
In any of the examples, precipitation of urea and ammonia odor were not observed, and it was confirmed that urea was stably maintained.
The residual amount of retinol palmitate was 87.5% in Example 3 and 88.2% in Example 6.
In Comparative Example 4, it was 78.8%, and in the examples of the present invention, the residual amount of the retinol derivative was improved by about 10% compared to the comparative example.

Test Example 4 Irritation test
About Examples 1-6 of Table 1, in order to evaluate the presence or absence of irritation, 0.5 g of the preparation was applied to the upper arm of each of the three monitors, and the skin condition after application (whether redness was present) And evaluated whether there was a feeling of irritation (feeling tingling, itching and burning).
As a result, in all the examples, all three monitors did not feel irritation, and it was confirmed that the examples of the present invention are safe and have no irritation.

Test Example 5 Skin Roughness Improvement Effect Evaluation Test
About Example 6 of Table 1, the rough skin improvement effect was evaluated. Specifically, for 10 women in their 30s who had severely affected areas of rough hands, an appropriate amount was applied to the affected areas and back of the normal skin for 4 weeks when they were concerned about bedtime and dryness. . After 1 week, 2 weeks and 4 weeks after the start of application, the electrical conductivity (μs) of the affected area of the hand and the back of the hand was measured with a surface angle layer moisture measuring device (SKICON-200EX, manufactured by IBS Corp.). did.
Relative values of the electrical conductivity at 1 week, 2 weeks and 4 weeks after the start of application were calculated, assuming that the electrical conductivity of the rough hand affected area before application and the back of the hand were 1, respectively.
The results are shown in Table 3.

The application of Example 6 markedly increased the water content in the affected area with severe hand roughness. Moreover, in all 10 women, management skills improved after 4 weeks. In addition, an increase in water content was also observed on the back of the hand compared to before application.
From the above results, it has been clarified that the present invention is excellent in the effect of normalizing keratin and improving touch.

The formulation examples are given below. In addition, the compounding quantity in the following Examples represents weight% about all the things which have no description of a unit especially.

Claims (6)

(A) 10-20% by weight of urea,
(B) retinol acetate, 0.5 wt% of one or more members selected from the group consisting of retinol palmitate and δ- retinoic acid tocopherol, and (C) tocopherol or tocopherol acetate, tocopherol nicotinate, tocopherol linolenic acid, A skin external preparation containing a tocopherol derivative selected from tocopherol succinate or a salt thereof. The skin external preparation of Claim 1 containing 1-300 weight part of component (A) with respect to 1 weight part of component (B). The skin external preparation of Claim 1 or 2 which contains a component (C) 0.001-5 weight%. Furthermore, the skin external preparation of any one of Claims 1-3 containing a component (D) higher alcohol. The higher alcohol of component (D) is one or more selected from lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, isostearyl alcohol, 2-octyldodecanol, behenyl alcohol, and 2-hexyldecanol. 4. An external preparation for skin according to 4. The skin external preparation according to any one of claims 1 to 5, which is an oil-in-water ointment, an oily, lotion-like, emulsion or aerosol-like liquid, gel or cream.