JP2002080358A - Skin care preparatoin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin care preparation that shows good affinity for skin with no problem of the stability and safety and can exert the effect of protecting the skin from being damaged. SOLUTION: One or more than two of elastins and mucopoly-saccharides, one or more than two selected from compounds bearing sulfhydryl group and compounds bearing disulfide bonds, one or more than two selected from nucleic acids and their salts, one or more than two selected from phspholipids and glycolipid, and one or more than two of flavonoids are individually adsorbed into hydroxyapatite and formulated to the base whereby the objective skin care preparation is obtained.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin which promotes skin turnover and is effective for preventing and improving skin damage.

[0002]

2. Description of the Related Art Skin is exposed to environmental factors such as ultraviolet rays, heat and dryness, and stresses caused by chemical substances, and is susceptible to damage by these factors. In order to prevent and improve such skin damage, amino acids and their metabolites, humectants such as polyhydric alcohols, emollients such as ester oils and vegetable oils, various ultraviolet absorbers, glycyrrhetinic acid and its derivatives, glycyrrhizinate , Allantoin, azulene and other anti-inflammatory agents, zinc oxide, zinc sulfate, allantoin hydroxyaluminum, tannic acid, citric acid and other astringents,
Various vitamins have been used.

[0003] Recently, a component that activates skin cells to promote skin turnover and a component that activates dermal fibroblasts to promote the biosynthesis of mucopolysaccharides such as hyaluronic acid and matrix components such as collagen. The search for such components is being actively pursued.

[0004] However, the above-mentioned components reported so far have insufficient stability in the preparation, have a transient effect, have low affinity for the skin, and have the expected effect. In some cases, it cannot be obtained, gives an unpleasant irritating feeling to the skin, or causes undesired side effects due to continuous use, and few of them have sufficient effect of preventing and improving skin damage.

[0005]

Accordingly, in the present invention, there is provided a skin external preparation which has no problem in stability and safety, shows good skin affinity, and can exert an excellent effect of protecting skin from damage. It was aimed at.

[0006]

Means for Solving the Problems As a result of various studies to solve the above problems, it has been found that by adsorbing specific proteins and polysaccharides to hydroxyapatite and including the same in an external preparation for skin, the affinity of such components for skin is improved. The present invention has been found to improve the skin, significantly promote the turnover of the skin, and exert the effect of favorably preventing and improving the damage to the skin, thereby completing the present invention.

That is, in the present invention, one or more selected from elastin and mucopolysaccharide, which are constituents of the dermal matrix, and a compound selected from a compound having a sulfhydryl group involved in redox control and a compound having a disulfide bond Species or two or more, one or more of nucleic acids and salts thereof having a cell activating effect, one or two or more selected from phospholipids and glycolipids having various physiological actions, such as lipids constituting biological membranes. At least one or more selected from flavonoids, which are components having an antioxidant action, are respectively adsorbed to hydroxyapatite and contained in a skin external preparation base.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Hydroxyapatite used in the present invention is represented by the chemical formula of Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ , and is widely used as an adsorbent for chromatography and a biomaterial such as an artificial tooth root. For the purpose of the present invention, commercially available hydroxyapatite powder can be used.

Next, the components adsorbed on hydroxyapatite in the present invention will be described.

[0010] First, elastin is a structural protein found in highly extensible tissues such as arteries, tendons, and skin.
For the purpose of the present invention, solubilized and hydrolysed products of elastin extracted from animal tissues, and those modified by chemical or enzymatic methods are preferably used,
Water-soluble elastin obtained by solubilizing elastin extracted from bovine neck tendon by heat treatment with oxalic acid, elastin hydrolyzate obtained by hydrolyzing bovine nodal ligament, elastase from cod fish skin Elastin hydrolyzate obtained by treatment, their methylsilanol,
Condensates such as N-acetylmethionine and lactic acid and salts thereof are exemplified.

In the present invention, elastin extracted from animal tissues as needed and prepared by solubilization or the like may be used, but commercially available products provided by various companies as raw materials for cosmetics and pharmaceuticals may be used. Is more preferable in terms of quality and price.

Next, mucopolysaccharides are long-chain polysaccharides composed of repeating units of a disaccharide composed of hexosamine and uronic acid.
Conventionally, it has been widely used as a moisturizer in skin external preparations. Keratan sulfate, chondroitin, chondroitin-4-sulfate (chondroitin sulfate A), dermatan sulfate (chondroitin sulfate B), chondroitin-6-sulfate (chondroitin sulfate C), chondroitin sulfate D, chondroitin
-4,6-sulfuric acid (chondroitin sulfate E), teicuronic acid,
Examples include hyaluronic acid, heparan sulfate, heparin and the like. In addition, alkali metal salts such as sodium salt and potassium salt, inorganic salts such as hydrochloride, sulfate, and ammonium salt, organic salts such as lactate, acetate, and triethanolamine salt, and alkyl, alkenyl, and aryl esters And derivatives such as phosphates, sulfates, and condensates with reducing sugars such as glucose, galactose, maltose, and lactose.

In the present invention, as the above mucopolysaccharides, those derived from animals and plants, algae, microorganisms, etc., those derived from nature, those synthesized by chemical or enzymatic reaction, lactic acid bacteria, etc. Produced by a fermentation method using the above microorganism can be used. In order to ensure more uniform quality, it is preferable to use those commercially available as raw materials for pharmaceuticals and cosmetics from various companies.

Subsequently, compounds having a sulfhydryl group include L-cysteine, D-cysteine, DL-cysteine, L-homocysteine, D-homocysteine, DL-homocysteine, cysteamine, dihydrolipoic acid, cysteinylglycine , Coenzyme A, reduced glutathione, reduced metallothionein, reduced thioredoxin, reduced midkine, and the like. Examples of the compound having a disulfide bond include L-cystine, D-cystine, DL-cystine, and L-cystine.
Homocystine, D-homocystine, DL-homocystine, lipoic acid, oxidized glutathione, oxidized metallothionein,
Oxidized thioredoxin, oxidized midkine and the like. Furthermore, salts such as alkali metal salts, hydrochlorides, sulfates, acetates, lactates, and ammonium salts, and derivatives such as alkyl or alkenyl esters, cholesteryl esters, phosphatidyl esters, amides, and glycosides can also be used. . In the present invention, those commercially available for cosmetics, pharmaceutical raw materials or reagents can be used.

The nucleic acids include DNA and RNA extracted from animals, plants, algae, and microorganisms, as well as chemical methods.
Alternatively, polynucleotides synthesized using an enzymatic reaction and salts thereof can be used. It is more preferable to use those commercially available for cosmetics and pharmaceuticals in terms of quality and the like.

Examples of the phospholipid include phosphatidic acid, lysophosphatidic acid, phosphatidylcholine (lecithin), lysophosphatidylcholine (lysolecithin), phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylserine, lysophosphatidylserine, phosphatidylglycerol, phosphatidylglycerol phosphate. Diphosphatidylglycerol (cardiolipin), acylphosphatidylglycerol, lysobisphosphatidic acid, bisphosphatidic acid, sugar ether of phosphatidylglycerol, phosphatidylglycerol-O-amino acid ester, phosphatidylinositol-4-phosphate, phosphatidylinositol-3,4-bisphosphate Glycero such as acid and phosphatidylinositol mannoside Glycerophosphonolipids such as sphingolipid, sphingomyelin, ceramide phosphoethanolamine, ceramide phosphoglycerol, ceramide phosphoglycerol phosphate, ceramide phosphoinositol and derivatives thereof, glycerophosphonolipids such as phosphatidylethylamine, ceramide phosphonoethylamine, ceramide phosphono N -Sphingphosphonolipids such as -methylethylamine and the like.

Examples of glycolipids include monoglycosylceramides such as galactocerebroside, psychosine, glucocerebroside, and glucopsychosin; diglycosylceramides such as cytolipin H and galabiosylceramide; glopotriglycosylceramide; and glopoisotriglycosylceramide. , Triglycosyl ceramides such as gangliotriglycosyl ceramide, glopotetraglycosyl ceramide (cytolipin K), glopoisotetraglycosyl ceramide (cytolipin R), tetraglycosyls such as gangliotetraglycosyl ceramide, lactone neotetraosyl ceramide Gangliosides such as ceramide, monosialoganglioside, disialoganglioside, and trisialoganglioside; glycosphingolipids such as ceramide glucuronic acid; and diacylglycerides Monoglycosyl diacyl glycerol, diacyl glycerol glucobioside, diacyl glycerol galactobioside, diacyl glycerol lactoside, etc. diglycosyl diacyl glycerol, diacyl glycerol glucotrioside, diacyl glycerol galacto trioside, etc. Glyceroglycolipids such as triglycosyldiacylglycerol and sulfogalactoglycerolipid, and glucuronic acid-containing glyceroglycolipids.

In the present invention, as the above phospholipid and glycolipid, those derived from animals and plants, algae, microorganisms, and other natural sources, and those synthesized using chemical or enzymatic reactions are used. Can be. Further, natural phospholipids and glycolipids obtained by subjecting them to chemical modification such as hydrogenation, and derivatives obtained by transesterification or the like from natural or synthetic phospholipids can also be used. The lipid may be obtained by extracting, fractionating, or synthesizing it from a natural material, or commercially available as a raw material for cosmetics and pharmaceuticals. An object of the present invention is to provide phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol or ceramide phosphoinositol derived from plants or algae or yeast, or hydrogenated products thereof, or phosphatidyl esters of 2-hydroxy acids, phosphatidylglucosamine, phosphatidyl. Phosphatidic acid derivatives such as cysteine and phosphatidyl glutathione are particularly preferably used.

Finally, flavonoids are a general term for a group of substances that are widely contained in plants and in which two phenyl groups are bonded via three carbon atoms in a pyran ring or a structure similar thereto. Flavones such as flavone, chrysin and its glycoside, apigenin and its glycoside, luteolin and its glycoside, kaempferol and its glycoside, quercetin and its glycoside, myricetin and its glycoside, etc. Flavonols, daidzein and its glycosides, isoflavones such as genistein and its glycosides, pinocembrin, naringenin and its glycosides, sakuranetin and its glycosides, hesperetin and its glycosides, eriodictyol, mattishi Flavonones such as phenol, pinobanksin, aromadendrin and its glycosides, fustin, taxifolin and its derivatives, flavanonols such as amperoptin, butein and its glycosides, carconocartamidine and its glycosides, pedicin, pedicinin Chalcones, such as sulfretin and its Anthocyans such as carbohydrates, leptosidine and its glycosides, benzalkumaranones such as aureucidine and its glycosides, pelargonidin and its glycosides, cyanidin and its glycosides, delphinidin and its glycosides, etc. Is mentioned.

In the present invention, purified products and synthetic products can be used in addition to the flavonoids extracted from plants. Commercially available products for cosmetics, pharmaceutical raw materials or reagents can also be used.

The above-mentioned elastin and mucopolysaccharides, compounds having a sulfhydryl group and compounds having a disulfide bond, nucleic acids and salts thereof, phospholipids and glycolipids, and flavonoids are selected from one or more of hydroxyapatite. To be absorbed. The adsorption of the components to be adsorbed can be performed by either a wet treatment or a dry treatment. In the wet treatment, the component to be adsorbed is appropriately dissolved in a solvent, added to the hydroxyapatite powder and kneaded and then dried, or the hydroxyapatite powder is mixed with a solution of the component to be adsorbed and stirred, and then centrifuged. Alternatively, a method may be employed in which the adsorbed powder is collected by filtration and then dried. It is appropriate that the mixing ratio of the hydroxyapatite powder and the solution of the component to be adsorbed is about 10: 1 to 1:10 by weight. In the dry treatment, a component to be adsorbed in a powder form by freeze-drying, crystallization or the like is mixed with a hydroxyapatite powder and stirred. In this case, the mixing ratio of the hydroxyapatite powder and the component to be adsorbed is suitably about 20: 1 to 1: 2 by weight.

The above-mentioned adsorption treatment is preferably carried out at a low temperature as much as possible, and is suitably carried out in the range of 0 ° C. to 25 ° C. The treatment time varies depending on the mixing ratio of the component to be adsorbed and hydroxyapatite and the type of the component to be adsorbed.
It is appropriate to set the time to about 24 hours. The adsorption-treated hydroxyapatite powder thus obtained can be contained as it is in an external preparation for skin. However, depending on the purpose, hydrophobic treatment such as silicone treatment, metal soap treatment, or fluororesin treatment may be performed. , Chemical treatment,
The coated material can be used after being subjected to a fixing treatment by a low-temperature plasma surface treatment or the like.

In the present invention, one or more of hydroxyapatite powder adsorbed by the above-mentioned components to be adsorbed is contained in a skin external preparation base. Further, in the present invention, other oily components, as long as the characteristics of the present invention are not impaired,
Surfactants, humectants, pigments, UV absorbers, antioxidants,
Raw materials for general pharmaceuticals and cosmetics such as fragrances and fungicides and fungicides, and physiologically active ingredients such as skin cell activators, anti-inflammatory agents and whitening agents can also be contained.

The external preparation for skin according to the present invention can be provided in various dosage forms such as lotions, emulsions, gels, creams, ointments, powders, granules and the like. Also, skin cosmetics such as lotion, milky lotion, cream, serum, pack, etc.
Makeup base lotion, base makeup such as makeup base cream, foundation of various dosage forms such as milky liquid, oily and solid, makeup cosmetics such as eye color, cheek color, etc., cleansing cream, cleansing lotion, cleansing foam It can also be provided as a skin cleanser such as facial soap and body shampoo, and a body cosmetic such as body lotion, hand cream and leg cream.

[0025]

EXAMPLES Further, the features of the present invention will be described in detail with reference to examples.

First, a preparation example of the adsorption-treated hydroxyapatite powder used in the present invention will be described.

[Preparation Example 1] Elastin hydrolyzate-adsorbed hydroxyapatite 20 g of a commercially available elastin hydrolyzate derived from bovine ligament was added to 100 g of hydroxyapatite, kneaded at 10 ° C for 2 hours, and then air-dried.

[Preparation Example 2] Sodium hyaluronate-adsorbed hydroxyapatite 500 g of a 1.0% by weight aqueous solution of sodium hyaluronate
Was added and mixed with gentle stirring at 10 ° C. for 4 hours. Then, the powder was collected by filtration and air-dried.

[Preparation Example 3] Chondroitin-4,6-sulfuric acid-adsorbed hydroxyapatite A 1.0% by weight aqueous solution of chondroitin-4,6-sulfuric acid 500
100 g of hydroxyapatite to 10 g
For 4 hours with gentle stirring. Then, the powder was collected by filtration and air-dried.

Preparation Example 4 L-Cysteine-Adsorbed Hydroxyapatite 100 g of hydroxyapatite was added to 1,000 g of a 2.0% by weight aqueous solution of L-cysteine and mixed at 20 ° C. for 2 hours with gentle stirring. Then, the powder was collected by filtration and air-dried.

Preparation Example 5 Metallothionein-Adsorbed Hydroxyapatite To 1,000 g of a 1.0% by weight aqueous solution of metallothionein, 250 g of hydroxyapatite was added and mixed at 4 ° C. with gentle stirring for 6 hours. Then, the powder was collected by filtration and air-dried.

[Preparation Example 6] Thioredoxin-Adsorbed Hydroxyapatite To 1,000 g of a 1.0% by weight aqueous solution of thioredoxin, 250 g of hydroxyapatite was added and mixed with gentle stirring at 4 ° C for 6 hours. Then, the powder was collected by filtration and air-dried.

[Preparation Example 7] Deoxyribonucleic acid potassium salt-adsorbed hydroxyapatite A commercially available salmonid ( Salmonidae ) fish testis-derived 15 g potassium salt of deoxyribonucleic acid was added to hydroxyapatite 20
0 g, and mixed for 4 hours while maintaining the temperature of the mixing tank at 10 ° C. or lower.

[Preparation Example 8] Soybean lecithin-adsorbed hydroxyapatite Commercially available 1.0% by weight soybean lecithin ethanol solution 20
g was added to 100 g of hydroxyapatite, kneaded at 15 ° C. for 4 hours, and then dried.

Preparation Example 9 Sphingomyelin-Adsorbed Hydroxyapatite 20 g of reagent grade sphingomyelin was added to 100 g of hydroxyapatite, and the mixture was mixed for 4 hours while maintaining the temperature of the mixing tank at 15 ° C. or lower.

[Preparation Example 10] Hydroxyapatite adsorbed with daidzein 25 g of a 1.0% by weight ethanol solution of daidzein obtained by extraction from cuckoo was mixed with hydroxyapatite 100
g and mixed at 10 ° C. for 6 hours with gentle stirring. Then, the powder was collected by filtration and air-dried.

Preparation Example 11 Epicatechin-Adsorbed Hydroxyapatite A 1.0% by weight ethanol solution of reagent grade epicatechin 25
g was added to 100 g of hydroxyapatite and mixed with gentle stirring at 10 ° C. for 6 hours. Then, the powder was collected by filtration and air-dried.

Preparation Example 12 Rutin-Adsorbed Hydroxyapatite 25 g of a 1.0% by weight ethanol solution of reagent grade rutin was added to 100 g of hydroxyapatite, and mixed at 10 ° C. for 6 hours with gentle stirring. Then, the powder was collected by filtration and air-dried.

The adsorption-treated hydroxyapatite of Preparation Examples 1 to 6 was subjected to a metal soap treatment according to a conventional method to make it hydrophobic, thereby obtaining Preparation Examples 13 to 18.

Next, the formulations of Examples for the external preparation for skin according to the present invention will be shown.

Example 1 Two-Layered Lotion Agent (1) Ethanol 10.0 (% by weight) (2) Polyoxyethylene (60E.O.) Hydrogenated Castor Oil 1.0 (3) Methyl paraoxybenzoate 1 (4) Dipropylene glycol 5.0 (5) 1,3-butylene glycol 10.0 (6) Purified water 68.9 (7) Elastin hydrolyzate-adsorbed hydroxy 5.0 apatite (Preparation Example 1) Production method: (2) and (3) are added to (1) and dissolved to form an alcohol phase. On the other hand, (4) and (5) are sequentially dissolved in (6), and then (7)
To form an aqueous phase. Add the alcohol phase to the aqueous phase,
Stir and mix.

Example 2 Emulsion (1) Cetanol 1.0 (% by weight) (2) Beeswax 0.5 (3) Vaseline 2.0 (4) Squalane 6.0 (5) Dimethylpolysiloxane 2.0 (6) polyoxyethylene (20E.O.) sorbitan 1.0 monostearate (7) glyceryl monostearate 1.0 (8) glycerin 4.0 (9) 1,3-butylene glycol 4.0 (10) Methyl paraoxybenzoate 0.1 (11) Purified water 62.8 (12) Carboxyvinyl polymer 10.0 (1.0% by weight aqueous solution) (13) Potassium hydroxide 0.1 (14) Sodium hyaluronate Adsorbed hydroxy 5.5 apatite (Preparation Example 2) Production method: The oil phase components (1) to (7) are mixed and dissolved by heating to 75
° C. On the other hand, the aqueous phase components (8) to (11) are mixed and dissolved to 75 ° C. The oil phase was added thereto, and the mixture was pre-emulsified. (12) was added, and the mixture was uniformly emulsified with a homomixer. Is added and dispersed.

Example 3 Oil-in-water Cream (1) Beeswax 6.0 (% by weight) (2) Cetanol 5.0 (3) Reduced Lanolin 8.0 (4) Squalane 27.5 (5) Glyceryl Fatty acid ester 4.0 (6) Lipophilic glyceryl monostearate 2.0 (7) Polyoxyethylene (20E.O.) sorbitan 5.0 Monolaurate (8) Propylene glycol 5.0 (9) Paraoxy Methyl benzoate 0.1 (10) Purified water 27.4 (11) Chondroitin-4,6-sulfuric acid-adsorbed hydroxy 5.0 apatite (Preparation Example 3) (12) Daidzein-adsorbed hydroxyapatite 5.0 (Preparation Example 10) Production method: The oil phase components (1) to (7) are mixed and dissolved to 75 ° C. On the other hand, the aqueous phase components (8) to (10)
Heat to ° C. Next, the oil phase component is added to the aqueous phase component and pre-emulsified, and then uniformly emulsified by a homomixer. After cooling, (11) and (12) are added and dispersed at 40 ° C.

Example 4 Gel Preparation (1) Dipropylene glycol 10.0 (% by weight) (2) Carboxyvinyl polymer 0.5 (3) Potassium hydroxide 0.1 (4) Methyl paraoxybenzoate 1 (5) Purified water 83.3 (6) L-cysteine-adsorbed hydroxyapatite 3.0 (Preparation Example 4) (7) Deoxyribonucleic acid potassium salt-adsorbed hydroxy3.0 apatite (Preparation Example 7) Production method: (5) After uniformly dissolving (2), (4) is dissolved and added to (1), and then (3) is added to increase the viscosity. Then (6),
(7) is added and dispersed.

Example 5 Oil-in-Water Emulsion Ointment (1) White Vaseline 25.0 (% by weight) (2) Stearyl Alcohol 25.0 (3) Glycerin 12.0 (4) Sodium Lauryl Sulfate 1.0 (5) Methyl paraoxybenzoate 0.1 (6) Purified water 30.9 (7) Metallothionein-adsorbed hydroxyapatite 1.5 (Preparation Example 5) (8) Thioredoxin-adsorbed hydroxyapatite 1.5 (Preparation Example 6) (9) ) Epicatechin-adsorbed hydroxyapatite 3.0 (Preparation Example 11) Production method: The oil phase components (1) to (4) are mixed and heated to uniformly dissolve, and the mixture is heated to 75 ° C. On the other hand, the aqueous phase components of (5) and (6) are mixed,
Heat to 75 ° C. The oil phase component was gradually added to the water phase component with stirring to emulsify, and after cooling, 40
Add (7) to (9) at ℃ and disperse.

Example 6 Water-in-oil Emollient Cream (1) Liquid Paraffin 30.0 (wt%) (2) Microcrystalline Wax 2.0 (3) Vaseline 5.0 (4) Diglyceryl Dioleate Ester 5.0 (5) Sodium L-glutamate 1.6 (6) L-Serine 0.4 (7) Propylene glycol 3.0 (8) Methyl parahydroxybenzoate 0.1 (9) Soybean lecithin-adsorbed hydroxyapatite 1 5.5 (Preparation Example 8) (10) Purified water 49.8 (11) Fragrance 0.1 (12) Hydrophobizing treatment Sodium hyaluronate adsorption 1.5 Hydroxyapatite (Preparation Example 14) Production method: (5), (6) ) Is dissolved in a part of (10) to 50 ° C., and gradually added to (4) heated to 50 ° C. with stirring. This is mixed in advance, and is uniformly dispersed in (1) to (3) heated and dissolved at 70 ° C. To this, (8) is dissolved in (7), added to (9) together with the remainder of (10), heated at 70 ° C. is added with stirring, and emulsified with a homomixer. After cooling, (11) and (12) are added at 40 ° C., and mixed and dispersed.

Example 7 Makeup Base Cream (1) Stearic acid 12.0 (% by weight) (2) Cetanol 2.0 (3) Glyceryl tri-2-ethylhexanoate 2.5 (4) Self-emulsification Type glyceryl monostearic acid 2.0 ester (5) Propylene glycol 10.0 (6) Potassium hydroxide 0.3 (7) Methyl paraoxybenzoate 0.1 (8) Purified water 66.5 (9) Titanium oxide 2 0.0 (10) Bengala 0.4 (11) Yellow iron oxide 0.1 (12) Rutin-adsorbed hydroxyapatite 2.0 (Preparation Example 12) (13) Fragrance 0.1 Manufacturing method: (1) to (4) The oil phase components are mixed and dissolved to 75 ° C. On the other hand, the aqueous phase components of (5) to (8) were mixed and dissolved by heating, and the pigment components of (9) to (11) and (12) were added thereto, and the mixture was uniformly dispersed by a homomixer. ° C. Next, the oil phase component is added to the water phase component, and the mixture is uniformly emulsified with a homomixer. After cooling, (13) is added and mixed at 40 ° C.

Example 8 Emulsion Foundation (1) Stearic acid 2.00 (% by weight) (2) Squalane 5.00 (3) Octyldodecyl myristate 5.00 (4) Cetanol 1.00 (5) Decaglyceryl monoisopalmitate 9.00 (6) 1,3-butylene crychol 6.00 (7) Potassium hydroxide 0.08 (8) Methyl parahydroxybenzoate 0.10 (9) Purified water 51.07 (10) Titanium oxide 9.00 (11) Talc 7.40 (12) Bengala 0.50 (13) Yellow iron oxide 1.10 (14) Black iron oxide 0.10 (15) L-cysteine adsorbed hydroxyapatite 1 .50 (Preparation Example 4) (16) Epicatechin-Adsorbed Hydroxyapatite 1.00 (Preparation Example 11) (17) Fragrance 0.15 Production Method: Mix and dissolve the oil phase components of (1) to (5) to 75 ° C. On the other hand, the aqueous phase components (6) to (9) are mixed and dissolved by heating, and the pigment components (10) to (14) and (15) and (16) are added thereto, and the mixture is homogenized with a homomixer. Disperse to 75 ° C. Next, the oil phase component is added to the aqueous phase component, and the mixture is uniformly emulsified with a homomixer. After cooling, (17) is added and mixed at 40 ° C.

[Example 9] Oily foundation (1) Solid paraffin 3.0 (wt%) (2) Microcrystalline wax 6.0 (3) Beeswax 2.0 (4) Vaseline 12.0 (5) Lanolin acetate 1.0 (6) Squalane 6.0 (7) Isopropyl palmitate 16.2 (8) d-δ-tocopherol 0.2 (9) Sphingomyelin-adsorbed hydroxyapatite 1.5 (Preparation Example 9) (10) Hydrophobic L-cysteine-adsorbed hydroxy 1.5 apatite (Preparation Example 16) (11) Talc 16.3 (12) Kaolin 15.0 (13) Titanium oxide 15.0 (14) Bengala 1.0 (15) Yellow oxidation Iron 3.0 (16) Black iron oxide 0.2 (17) Fragrance 0.1 Production method: After dissolving (1) to (8) at 85 ° C, adding (9) and (10) and dispersing , Previously mixed and crushed (11)-(16) Stirring while adding, triturated dispersed in a colloid mill. Next, (17) is added, and after degassing, the mixture is poured into a container at 70 ° C. and cooled.

Example 10 Powdery Foundation (1) Liquid paraffin 7.0 (% by weight) (2) Octyldodecyl myristate 2.5 (3) Vaseline 2.5 (4) Methyl paraoxybenzoate 0.1 ( 5) Fragrance 0.1 (6) Hydrophobized treatment chondroitin-4,6-sulfuric acid adsorption 1.0 hydroxyapatite (Preparation Example 15) (7) Hydrophobization treatment metallothionein-adsorbed hydroxy 1.5 apatite (Preparation Example 17) (8) ) Titanium oxide 10.0 (9) Nylon powder 10.0 (10) Mica 20.0 (11) Talc 39.8 (12) Bengala 3.0 (13) Yellow iron oxide 2.0 (14) Black iron oxide 0.5 Production method: The pigment components of (8) to (14) are mixed and pulverized through a pulverizer. This is transferred to a high-speed blender, and (6) and (7) are dispersed and added to the mixture of (1) to (5), followed by uniform mixing. This is processed by a pulverizer, passed through a sieve to adjust the particle size, and then filled in a gold plate and compression-molded.

Example 11 Two-way Foundation (1) Liquid paraffin 4.0 (% by weight) (2) Squalane 2.0 (3) Methylphenyl polysiloxane 4.0 (4) Methyl paraoxybenzoate 0.1 ( 5) Fragrance 0.1 (6) Hydrophobized treatment elastin hydrolyzate adsorption 2.0 hydroxyapatite (Preparation Example 13) (7) Hydrophobization treatment thioredoxin-adsorbed hydroxy 1.5 apatite (Preparation Example 18) (8) Silicone treatment Titanium oxide 10.0 (9) Silicone treated sericite 25.0 (10) Silicone treated talc 31.7 (11) Silicone treated kaolin 5.0 (12) Silicone treated bengara 2.5 (13) Silicone treated iron oxide yellow 2.0 (14) Silicone-treated black iron oxide 0.1 (15) Polyethylene powder 10.0 Manufacturing method: faces of (6) to (15) The ingredients were mixed and ground through grinder. This is transferred to a high-speed blender, and (1) to (5) are mixed and added, and mixed uniformly. This is processed in a crusher,
After passing through a sieve to adjust the particle size, the mixture is filled in a metal plate and compression molded.

Example 12 Hand Cream (1) Cetanol 4.00 (% by weight) (2) Vaseline 2.00 (3) Liquid paraffin 10.00 (4) Glyceryl monostearate 1.50 (5) Polyoxyethylene (60E.O.) glyceryl 2.50 isostearate (6) tocopherol acetate 0.25 (7) glycerin 20.00 (8) methyl paraoxybenzoate 0.10 (9) purified water 58.65 ( 10) Thioredoxin-adsorbed hydroxyapatite 0.25 (Preparation Example 6) (11) Deoxyribonucleic acid potassium salt adsorption 0.50 hydroxyapatite (Preparation Example 7) (12) Rutin-adsorbed hydroxyapatite 0.25 (Preparation Example 12) Production method: Mix and dissolve the oil phase components of 1) to (6) to 75 ° C. On the other hand, the aqueous phase components (7) to (9) were mixed and dissolved by heating.
5 ° C. Next, the oil phase component was added to the water phase component, and the mixture was uniformly emulsified with a homomixer.
Add and disperse (10) to (12).

Of the above-described embodiments of the present invention, Embodiment 1
The wound healing effect of Example 5 was evaluated. that time,
Comparative examples 1 to 10 prepared by substituting the adsorption-treated hydroxyapatite according to each preparation example blended in each example as shown in Table 1 were also evaluated at the same time.

[0054]

[Table 1]

[0055] The wound healing effect was determined by grouping five hairless mice having an artificially formed wound on the back as a group, and applying the examples and comparative examples twice a day to the wound site in each group for 7 days. The wound healing status on the 8th day was observed and evaluated. The wound healing status is “completely healed”, “almost healed”,
Table 2 shows the number of hairless mice that were evaluated in three stages of “incomplete healing” and obtained each evaluation.

[0056]

[Table 2]

As is clear from Table 2, wound healing was observed in all groups in the group to which the examples of the present invention were applied, and wound healing was complete in two or more hairless mice. On the other hand, Comparative Example 1, Comparative Example 3, Comparative Example 5, Comparative Example 7, and Comparative Example 9 in which the adsorption-treated hydroxyapatite according to each preparation example was replaced with hydroxyapatite not subjected to such an adsorption treatment, Healing of a terrible wound was not observed, and only a certain degree of healing was observed in one case in the application group of Comparative Example 5. In Comparative Examples 2, Comparative Examples 4, Comparative Examples 6, Comparative Examples 8, and Comparative Examples 10 and 10 each containing only the component adsorbed on hydroxyapatite in each Preparation Example, the content of each component in each Comparative Example However, the healing effect of the wound was much smaller than that of the corresponding group to which each of the Examples was applied, though the amount was substantially equal to or more than the amount substantially contained in each Example.

Subsequently, Examples 1 to 1 according to the present invention
For No. 2, the effect of improving skin roughness was evaluated by a use test. At that time, the adsorption-treated hydroxyapatite according to each of the preparation examples was added to sorbitol in Examples 1 to 5, Examples 7, 8 and 12, and to jojoba oil in Examples 6 and 9. , Example 10 and Example 1
In Example 1, the talc obtained by substituting commercially available chitosan-coated talc was used as Comparative Examples 11 to 22, and the evaluation was performed at the same time.

The effect of improving skin roughness was determined by grouping 20 female panelists in their 20s and 60s who exhibited remarkable skin roughening symptoms twice a day in each group. The evaluation was performed by using continuously for two months.
The skin condition before and after the start of the use test was evaluated and scored according to the evaluation criteria shown in Table 3, and the average value of 20 persons was calculated and shown in Table 4.

[0060]

[Table 3]

[0061]

[Table 4]

As is evident from Table 4, in each of the groups using the examples of the present invention, improvement of the rough skin symptoms was observed in all cases, and the skin condition was recovered to almost a good state after the end of the use test. . On the other hand, in the comparative example using the adsorption-treated hydroxyapatite according to each of the preparation examples, sorbitol as a humectant or jojoba oil as an emollient, or talc coated with chitosan, the improvement of the rough skin symptoms is insufficient. there were.

During the above use test period, there was no panelist in the use group of the examples according to the present invention which recognized skin irritation and skin sensitization. In addition, there was no paneler who complained of discomfort such as burning and tingling during use. Furthermore, in Examples 1 to 12, no change in state was observed at all even when stored at 25 ° C for 6 months.

[0064]

As described in detail above, according to the present invention, an external preparation for skin which has good stability and safety and can exert an effect of protecting skin damage can be obtained.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 7/00 A61K 7/00 F JN Q R 7/02 7/02 Z 7/48 7/48 9 / 06 9/06 9/107 9/107 9/14 9/14 31/353 31/353 31/661 31/661 31/7036 31/7036 31/713 31/713 31/726 31/726 38/00 47/02 38/17 A61P 17/16 47/02 43/00 107 A61P 17/16 A61K 37/02 43/00 107 37/12 F term (reference) 4C076 AA06 AA09 AA17 AA29 BB31 CC18 DD26 DD37 DD38 DD45 DD46 FF16 FF36 4C083 AA082 AB032 AB232 AB242 AB291 AB292 AB432 AC012 AC022 AC072 AC102 AC122 AC242 AC352 AC422 AC432 AC442 AC482 AC561 AC562 AC771 AC772 AC782 AC841 AC842 AD022 AD072 AD092 AD112 AD152 AD311 AD332 AD342 AD391 AD411 AD412 AD512 AD571 AD572 CC602 DD601 DD31 DD32 DD33 DD41 EE01 EE05 EE12 4C084 AA02 BA01 BA03 BA0 8 BA14 BA15 BA26 CA25 DC50 MA02 MA05 MA28 MA43 MA63 NA03 ZA892 ZB222 4C086 AA01 AA02 BA08 DA41 DA42 EA06 EA16 EA25 EA26 EA27 MA02 MA03 MA05 MA10 MA28 MA43 MA63 NA03 ZA89 ZB22 4C206 AA01 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 MA03 ZA89 ZB22

Claims (5)

[Claims] 1. An external preparation for skin, characterized by containing hydroxyapatite obtained by adsorbing one or more selected from elastin and mucopolysaccharide. 2. One or two selected from a compound having a sulfhydryl group and a compound having a disulfide bond.
An external preparation for skin, comprising hydroxyapatite obtained by adsorbing at least one species. 3. An external preparation for skin, characterized by containing hydroxyapatite obtained by adsorbing one or more nucleic acids and salts thereof. 4. An external preparation for skin, comprising hydroxyapatite obtained by adsorbing one or more selected from phospholipids and glycolipids. 5. An external preparation for skin, comprising hydroxyapatite obtained by adsorbing one or more flavonoids.