HK1210709A1 - Composition for external use - Google Patents

Abstract

A composition for external use which comprises (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) a hydroxyalkylurea and which is practically sufficiently inhibited from suffering a decrease in viscosity with the lapse of time and a decrease in use feeling or humectant performance which accompanies the viscosity decrease.

Description

External composition

Technical Field

The present invention relates to a composition containing an acidic mucopolysaccharide, which is an external composition having stable properties of acidic mucopolysaccharides.

Background

Skin is exposed to various factors such as ultraviolet rays, external factors such as changes in temperature or humidity, and internal factors such as aging, and the like, and thus, the water retention function or the skin barrier function is lowered, thereby causing various troubles such as dryness, itching, rash, ulcer, and miliaria. In order to improve these symptoms, the cause is primarily eliminated, but it is effective to normalize the moisture retention function or skin barrier function by applying a pharmaceutical or cosmetic containing a moisture-retaining component.

As the compound having a moisturizing effect, hyaluronic acid, chondroitin sulfate, heparin, dermatan sulfate, heparan sulfate, keratan sulfate, and the like, which are mucopolysaccharides, are used. In the case of hyaluronic acid as a representative example, hyaluronic acid is a mucopolysaccharide containing glucuronic acid and N-acetylglucosamine, which is present in a large amount in the dermis so as to fill intercellular and interfibrous junction substances in the living body and is also found in the epidermis, and has high water retentivity and viscoelasticity. Based on such properties, the compound is used as a component of an eye drop for treating corneal epithelial disorders, an injection for treating knee osteoarthritis, or the like in the medical field, and is used as a moisturizer in the cosmetic field.

Thus, mucopolysaccharides are polysaccharide thickeners which are generally used as moisturizers of external preparations. It is known that, although a surfactant is often added to an external preparation in terms of a preparation, a feeling of use, or the like, mucopolysaccharides are used in combination with a surfactant to lower the viscosity. This viscosity reduction is particularly pronounced in the case of exposure of the composition to light, heat. The viscosity of mucopolysaccharides is reduced, and there is a problem that the feeling of moistening and firmness as the feeling of use of mucopolysaccharide-containing compositions is reduced. In addition, there is a problem that the moisturizing function of a composition containing mucopolysaccharides is impaired.

On the other hand, various methods for suppressing the decrease in viscosity of mucopolysaccharides with time have been proposed.

For example, patent document 1 teaches: an external preparation for skin containing high molecular weight hyaluronic acid, low molecular weight hyaluronic acid, polyhydric alcohol and edetate is suppressed in viscosity reduction with time and excellent in water retention performance.

In addition, patent document 2 teaches: by blending a specific vegetable oil in a composition for application to a mucous membrane containing hyaluronic acid or a salt thereof, a decrease in the viscosity of the composition is suppressed even when a surfactant is contained.

In addition, patent document 3 teaches: by blending a liquid composition for application to a mucous membrane, which contains a hyaluronic acid compound and a surfactant, with a fat-soluble vitamin, the decrease in viscosity of the composition is suppressed.

However, the compositions described in these documents are not practically sufficient in terms of the reduction in viscosity of mucopolysaccharides with time and the accompanying suppression of the deterioration of the feeling of use and moisture retention performance. In addition, since the compositions of patent documents 2 and 3 contain fat-soluble substances such as vegetable oils and fat-soluble vitamins, it is difficult to maintain the transparency of the compositions, and thus it is difficult to use the compositions for external use as cosmetics and the like.

Documents of the prior art

Patent document

Patent document 1: japanese laid-open patent publication No. Hei 1-190614

Patent document 2: japanese patent laid-open No. 2006-117656

Patent document 3: japanese Kokai publication No. 2004-359629

Disclosure of Invention

Problems to be solved by the invention

The invention provides an external composition containing acidic mucopolysaccharide, wherein the viscosity reduction with time and the reduction with time of the using feeling and moisture retention performance are fully inhibited in practical use.

Means for solving the problems

The present inventors have made extensive studies to solve the above problems, and found that when a compound having a polyoxyalkylene group is blended with an acidic mucopolysaccharide, the viscosity of the composition is easily decreased with time, but when hydroxyalkyl urea is further blended, the decrease in viscosity with time of the composition is significantly suppressed.

The present invention has been made based on the above findings, and provides the following composition for external use.

Item 1. an external composition containing (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) a hydroxyalkyl urea.

The composition for external use according to item 1, wherein the hydroxyalkyl urea is N- (2-hydroxyethyl) urea.

The composition of item 3 for external use according to item 1 or 2, wherein the acidic mucopolysaccharide is selected from the group consisting of hyaluronic acid and chondroitin sulfate and salts thereof.

The composition for external use according to any one of items 1 to 3, wherein the compound having a polyoxyalkylene group is polyoxybutylene polyoxyethylenepolyoxypropylene glycerin.

The composition for external use according to any one of items 1 to 4, wherein the hydroxyalkyl urea is contained in an amount of 0.0001 to 2000 parts by weight based on 1 part by weight of the polyoxyalkylene-containing compound.

The composition for external use according to any one of items 1 to 5, wherein the hydroxyalkyl urea is contained in an amount of 0.01 to 10000 parts by weight based on 1 part by weight of the acidic mucopolysaccharide.

The composition for external use according to any one of claims 1 to 6, wherein the acidic mucopolysaccharide is contained in an amount of 0.000001 to 1 wt% based on the total amount of the composition.

The composition for external use according to any one of items 1 to 7, wherein the hydroxyalkyl urea is contained in an amount of 0.001 to 30% by weight based on the total amount of the composition.

The composition for external use according to any one of items 1 to 8, wherein the polyoxyalkylene-containing compound is contained in an amount of 0.01 to 20% by weight based on the total amount of the composition.

The composition for external use according to any one of claims 1 to 9, which is for moisturizing.

The external composition according to any one of items 1 to 9, which is used for imparting a firm feeling to the skin.

The method according to item 12, which comprises applying an external composition comprising (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) hydroxyalkyl urea to human skin to moisturize the skin or impart a moist, swollen, or firm feel to the skin.

The method of item 13, item 12, which is a non-therapeutic method.

The non-therapeutic use of a combination of (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) a hydroxyalkyl urea as a skin moisturizer or an agent for imparting a moist, swollen or firm feel to the skin.

Use of a combination of (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) a hydroxyalkyl urea for producing a skin moisturizer or an agent for imparting a moist, swollen or firm feel to the skin.

Effects of the invention

Acidic mucopolysaccharides are general-purpose components added to external compositions for imparting tackiness and moisturizing properties. On the other hand, a compound having a polyoxyalkylene group is commonly used as a component of a composition for external use because it functions as a nonionic surfactant, for example. However, when a compound having a polyoxyalkylene group is added to a composition containing an acidic mucopolysaccharide, the viscosity of the acidic mucopolysaccharide is impaired, and particularly the viscosity of the composition is significantly reduced when the composition is exposed to heat or light.

The composition for external use of the present invention further contains hydroxyalkyl urea in addition to the acidic mucopolysaccharide and the compound having a polyoxyalkylene group, whereby the decrease in viscosity of the composition is significantly suppressed even when exposed to heat or light. As a result, the moisturizing performance can be maintained for a long time, and a moist, puffy, and firm feeling can be imparted to the skin for a long time. In particular, a sense of firmness can be imparted.

Drawings

FIG. 1 is a diagram illustrating a viscosity measurement method in examples.

FIG. 2 is a graph showing the effect of hydroxyethyl urea on suppressing the decrease in viscosity of the composition. The vertical axis represents relative viscosity (%).

FIG. 3 is a graph showing the effect of hydroxyethyl urea on suppressing the decrease in viscosity of the composition. The vertical axis represents relative viscosity (%).

FIG. 4 is a graph showing the effect of hydroxyethyl urea on suppressing the decrease in viscosity of the composition. The vertical axis represents relative viscosity (%).

FIG. 5 is a graph showing the effect of hydroxyethyl urea on suppressing the decrease in viscosity of the composition. The vertical axis represents relative viscosity (%).

FIG. 6 is a graph showing the effect of hydroxyethyl urea on suppressing the decrease in viscosity of the composition. The vertical axis represents relative viscosity (%).

FIG. 7 is a graph showing the effect of hydroxyethyl urea on suppressing the decrease in viscosity of the composition. The vertical axis represents relative viscosity (%).

Detailed Description

The present invention will be described in detail below.

The composition for external use of the present invention is a composition containing (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) hydroxyalkyl urea.

(a) Acidic mucopolysaccharides

Acidic mucopolysaccharides are polysaccharides containing an amino sugar and an uronic acid in their basic skeleton. Specific examples of the acidic mucopolysaccharides include hyaluronic acid, chondroitin sulfate, heparin-like substances, dermatan sulfate, heparan sulfate, keratan sulfates I and II, and the like.

The acidic mucopolysaccharides may be natural products, or may be substances obtained by decomposing natural products by physical means such as acid, alkali, enzyme, ultrasonic wave, or shear, or derivatives of natural products.

For example, the hyaluronic acid may be a decomposed hyaluronic acid prepared by hydrolyzing a natural high molecular weight hyaluronic acid in the presence of an acid such as hydrochloric acid, treating the hyaluronic acid with an enzyme such as hyaluronidase, or physically cleaving the hyaluronic acid with ultrasonic waves or shear. The decomposed hyaluronic acid is commercially available as ヒアロオリゴ (manufactured by Kyoto Co., Ltd.).

Examples of the derivatives of natural products include acetylated hyaluronic acid and hydroxypropyltrimethylammonium chloride hyaluronic acid.

The acidic mucopolysaccharide may be natural product, decomposed product of natural product, or salt of their derivatives. Such salts may be pharmaceutically or biologically acceptable salts, and examples thereof include: alkali metal salts such as sodium and potassium; alkaline earth metal salts such as magnesium and calcium; a zinc salt; an ammonium salt; alkanolamine salts such as monoethanolamine. Among them, alkali metal salts are preferable, and sodium salts are more preferable.

Preferred examples of the acid mucopolysaccharide salt include sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, ammonium hyaluronate, hyaluronic acid monoethanolamine, acetylated sodium hyaluronate, acetylated potassium hyaluronate, acetylated calcium hyaluronate, acetylated magnesium hyaluronate, acetylated zinc hyaluronate, acetylated ammonium hyaluronate, acetylated hyaluronic acid monoethanolamine, chondroitin sulfate sodium, chondroitin sulfate potassium, dermatan sulfate sodium, dermatan sulfate potassium, chitosan ascorbic acid, chitosan glycolic acid, chitosan lactic acid, hydroxypropyl trimethyl ammonium chloride chitosan, heparan sulfate sodium, and heparan sulfate potassium.

Among the acidic mucopolysaccharides, hyaluronic acid, sodium hyaluronate, chondroitin sulfate, sodium acetylated hyaluronate, potassium acetylated hyaluronate, calcium acetylated hyaluronate, magnesium acetylated hyaluronate, and zinc acetylated hyaluronate are preferable, hyaluronic acid, sodium hyaluronate, chondroitin sulfate, sodium acetylated hyaluronate, potassium acetylated hyaluronate, and zinc acetylated hyaluronate are more preferable, and hyaluronic acid and sodium hyaluronate are even more preferable.

The acid mucopolysaccharides may be used singly or in combination of two or more.

The source of the acid mucopolysaccharide is not particularly limited, and may be an acid mucopolysaccharide that can be used in the fields of pharmaceuticals, quasi drugs, or cosmetics.

The average molecular weight of the acidic mucopolysaccharide is not particularly limited, and is, for example, about 1000 to 400 ten thousand, preferably about 1000 to 300 ten thousand, more preferably about 5000 to 300 ten thousand, and particularly preferably about 5000 to 200 ten thousand.

The content of the acidic mucopolysaccharides in the composition for external use is preferably 0.000001 wt% or more, more preferably 0.001 wt% or more, and still more preferably 0.01 wt% or more, based on the total amount of the composition. Within this range, sufficient tackiness and moisturizing properties can be imparted to the external composition. The content of the acidic mucopolysaccharides in the composition for external use is preferably 1 wt% or less, more preferably 0.5 wt% or less, and still more preferably 0.25 wt% or less, based on the total amount of the composition. When the content is within this range, stickiness can be suppressed, and a good feeling in use can be imparted.

(b) Compounds having polyoxyalkylene radicalsArticle (A)

The polyoxyalkylene group is a functional group represented by the following general formula (1).

(O(CH₂)m)n- (1)

In the functional group represented by the above formula (1) in the polyoxyalkylene group-containing compound used in the present invention, m is, for example, 1 to 4, preferably 2 to 4. Specific examples thereof include polyoxymethylene, polyoxyethylene, polyoxypropylene and polyoxybutylene.

In the formula (1), n is, for example, 2 to 150, preferably 5 to 100, and more preferably 10 to 30.

As the polyoxyalkylene group-containing compound, polyoxyalkylene glycerin ether in which a polyoxyalkylene group is bonded to 1 to 3 of three carbons of glycerin as a representative example. The fatty acid may be ester-bonded to a carbon to which the polyoxyalkylene group is not bonded.

Specific examples thereof include polyoxymethyleneglycerol ether, polyoxyethyleneglycerol ether, polyoxypropylene glycerol ether, polyoxybutyleglycerol ether, polyoxymethylenepolyoxyethyleneglycerol ether, polyoxymethylenepolyoxypropylene glycerol ether, polyoxymethylenepolyoxybutyleglycerol ether, polyoxyethylenepolyoxypropylene glycerol ether, polyoxyethylenepolyoxybutyleglycerol ether, polyoxypropyleneoxybutylelycerol ether, polyoxypropylene polyoxybutylelycerol ether, polyoxymethylenepolyoxyethylene polyoxypropylene glycerol ether, polyoxyethylenepolyoxybutyleneglycerol ether, polyoxypropylene polyoxypropyleneoxybutyleneglycerol ether, polyoxypropylene polyoxymethylenepolyoxybutyleneglycerol ether and polyoxypropylene polyoxymethylenepolyoxybutyleneglycerol ether.

Among them, glycerol ethers having a polyoxybutylene group are preferable, polyoxymethylenepolyoxyethylenepolyoxybutyleglycerol ether, polyoxybutyleneopolyoxyethylenepolyoxypropylene glycerol ether, polyoxypropylenepolyoxymethylenepolyoxybutyleglycerol ether are more preferable, and polyoxybutyleneopolyoxyethylenepolyoxypropylene glycerol ether is still more preferable.

As a commercially available product of polyoxybutylene polyoxyethylene polyoxypropylene glycerin ether, for example, ウィルブライド S-753 (manufactured by Nichikoku corporation; polyoxybutylene polyoxyethylene polyoxypropylene glycerin ether (3B.O) (8E.O) (5P.O)) and the like can be used.

Examples of the polyoxyalkylene glycerin ether having a fatty acid residue include polyoxyethylene glyceryl distearate, polyoxyethylene glyceryl tristearate, polyoxyethylene glyceryl isostearate, polyoxyethylene glyceryl triisostearate, polyoxyethylene glyceryl isostearate, polyoxyethylene glyceryl diisostearate, polyoxyethylene glyceryl triisostearate, polyoxyethylene glyceryl trioleate, polyoxyethylene glyceryl monostearate and the like.

The polyoxyalkylene group-containing compound may be used singly or in combination of two or more.

The content of the compound having a polyoxyalkylene group in the composition for external use is preferably 0.01% by weight or more, more preferably 0.05% by weight or more, and still more preferably 0.1% by weight or more, based on the total amount of the composition. When the amount is within this range, the effect of the compound having a polyoxyalkylene group can be obtained in a satisfactory manner. The content of the compound having a polyoxyalkylene group in the composition for external use is preferably 20% by weight or less, more preferably 15% by weight or less, and still more preferably 10% by weight or less, based on the total amount of the composition. When the content is within this range, a good feeling of use can be provided.

(c) Hydroxyalkyl ureas

The hydroxyalkyl urea refers to a compound in which at least one of hydrogen atoms of urea is substituted with hydroxyalkyl group. That is, the hydroxyalkyl urea in the present invention is a compound represented by the following general formula (2).

R¹R²N-CO-NR³R⁴ (2)

(in the formula, R¹、R²、R³And R⁴Each independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or a hydroxyalkyl group having 2 to 6 carbon atoms, and R¹、R²、R³And R⁴At least one of them is a hydroxyalkyl group having 2 to 6 carbon atoms)

Specific examples of the hydroxyalkyl group include hydroxyethyl, hydroxypropyl, hydroxybutyl, dihydroxybutyl, hydroxypentyl, and hydroxyhexyl. Among them, hydroxyethyl group is preferable.

More specifically, examples of the hydroxyalkyl urea include N- (2-hydroxyethyl) urea, N- (2-hydroxypropyl) urea, N- (3-hydroxypropyl) urea, N- (2, 3-dihydroxypropyl) urea, N- (2-hydroxybutyl) urea, N- (3-hydroxybutyl) urea, N- (4-hydroxybutyl) urea, N- (2, 3-dihydroxybutyl) urea, N- (2, 4-dihydroxybutyl) urea, N- (3, 4-dihydroxybutyl) urea, N-ethyl-N '- (2-hydroxyethyl) urea, N-bis (2-hydroxyethyl) urea, N' -bis (2-hydroxyethyl) urea, N-bis (2-hydroxypropyl) urea, N-hydroxypropyl urea, N- (2-hydroxypropyl) urea, N- (2-hydroxybutyl) urea, N- (4-hydroxybutyl) urea, N-bis (2-hydroxyethyl) urea, N, N, N ' -bis (2-hydroxypropyl) urea, N-bis (2-hydroxyethyl) -N ' -propylurea, N ' -bis (2-hydroxypropyl) -N ' - (2-hydroxyethyl) urea, N-tert-butyl-N ' - (2-hydroxyethyl) -N ' - (2-hydroxypropyl) urea, N-bis (2-hydroxyethyl) -N ', N ' -dimethylurea, N ' -tetrakis (2-hydroxyethyl) urea, and N, N-bis (2-hydroxyethyl) -N ', N ' -bis (2-hydroxypropyl) urea, and the like.

The number of hydroxyalkyl groups of hydroxyalkyl urea is preferably 1 to 3, more preferably 1 to 2, and still more preferably 1 (monohydroxyalkyl urea). Among them, hydroxyethyl urea is preferred.

The hydroxyalkyl ureas may be used singly or in combination of two or more.

The content of hydroxyalkyl urea in the composition for external use is preferably 0.001 wt% or more, more preferably 0.01 wt% or more, and still more preferably 0.1 wt% or more, based on the total amount of the composition. When the amount is within this range, the effects of the present invention (suppression of the deterioration of the performance of imparting the viscosity, moisturizing performance, moist feeling, and firm feeling of the composition with time) can be sufficiently obtained. The content of the hydroxyalkyl urea in the composition for external use is preferably 30% by weight or less, more preferably 20% by weight or less, and still more preferably 10% by weight or less, based on the total amount of the composition. Within this range, the effects of the present invention can be sufficiently obtained.

The ratio of the content of hydroxyalkyl urea to the content of the polyoxyalkylene compound is preferably 0.0001 part by weight or more, more preferably 0.01 part by weight or more, and still more preferably 0.1 part by weight or more, based on 1 part by weight of the polyoxyalkylene compound. When the amount is within this range, the effects of the present invention (suppression of the deterioration of the performance of imparting the viscosity, moisturizing performance, moist feeling, and firm feeling of the composition with time) can be sufficiently obtained. The ratio of the content of hydroxyalkyl urea to the content of the polyoxyalkylene compound is preferably 500 parts by weight or less, more preferably 200 parts by weight or less, and still more preferably 100 parts by weight or less, based on 1 part by weight of the polyoxyalkylene compound. Within this range, the effects of the present invention can be sufficiently obtained.

The ratio of the content of hydroxyalkyl urea to the content of acid mucopolysaccharide is preferably 0.01 parts by weight or more, more preferably 1 part by weight or more, and still more preferably 10 parts by weight or more, based on 1 part by weight of acid mucopolysaccharide. When the amount is within this range, the effects of the present invention (suppression of the deterioration of the performance of imparting the viscosity, moisturizing performance, moist feeling, and firm feeling of the composition with time) can be sufficiently obtained. The ratio of the content of hydroxyalkyl urea to the content of acid mucopolysaccharide is preferably 10000 parts by weight or less, more preferably 500 parts by weight or less, and still more preferably 100 parts by weight or less, based on 1 part by weight of acid mucopolysaccharide. Within this range, the effects of the present invention can be sufficiently obtained.

Preparation

The composition for external use of the present invention can be prepared, for example, by mixing the components (a) to (c) described above with a base or a carrier that can be used in cosmetics, and if necessary, additives and other active ingredients to prepare a composition for external use for cosmetics.

The composition is not particularly limited in its properties, and can be prepared into a liquid, flowable or semisolid preparation, for example, a liquid, a suspension, an emulsion, a cream, an ointment, a gel, a liniment, a lotion, an aerosol, a film obtained by impregnating a nonwoven fabric with a liquid drug, and the like. Among them, preferred are emulsions, creams, lotions, ointments, gels and lotions, and particularly preferred are creams, lotions, ointments and gels.

Specific uses of the cosmetic are not particularly limited, and examples thereof include basic cosmetics such as lotions, milky lotions, gels, creams, beauty liquids, sunscreen cosmetics, peel-off masks (pack), masks, hand creams, body lotions, and body creams; washing cosmetics such as cleansing products, makeup removers, bath foam, shampoos, hair conditioners, and conditioners; makeup base, various makeup cosmetics such as pastel and the like.

Base or carrier

As base or carrier, mention may be made of: hydrocarbons such as paraffin, liquid paraffin, squalane, white wax, gelled hydrocarbons (プラスチベース, etc.), ozokerite, ceresin, vaseline, stearin, microcrystalline wax, α -olefin oligomers, and light liquid paraffin; fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and isostearic acid; fatty acid triglycerides such as glycerol tri-2-ethylhexanoate (tricaprylin) and glycerol tri (caprylic/capric) ester; higher alcohols such as cetyl alcohol, stearyl alcohol and behenyl alcohol; methylpolysiloxane, high-polymerized methylpolysiloxane, dimethylsiloxane-methyl (polyoxyethylene) siloxane-methyl (polyoxypropylene) siloxane copolymer, dimethylsiloxane-methyl (polyoxyethylene) siloxane copolymer, dimethylsiloxane-methyl (polyoxypropylene) siloxane copolymer, polyoxyethylene-methylpolysiloxane copolymer, poly (oxyethylene-oxypropylene) methylpolysiloxane copolymer, dimethylsiloxane-methylcetyloxy siloxane copolymer, dimethylsiloxane-methylstearoxy siloxane copolymer, alkyl acrylate copolymer methylpolysiloxane ester, crosslinked methylpolysiloxane, crosslinked methylphenylpolysiloxane, crosslinked polyether-modified silicone, crosslinked alkyl-modified silicone, decamethylcyclopentasiloxane, poly (oxyethylene-co-methyl) siloxane copolymer, poly (oxyethylene-oxypropylene) -co-methyl siloxane copolymer, poly (oxyethylene-methyl-co-methyl siloxane copolymer, Silicone oils such as ethyltrisiloxane, methyltrimethylsiloxane, methylsiloxane network polymer, polyoxyethylene methylpolysiloxane copolymer, polymethylhydrosiloxane, triethoxysilylethylpolydimethylsilyloxyethylhexylpolydimethylsiloxane, and dimethylpolysiloxane; glycol acetates such as ethylene glycol monoacetate, ethylene glycol diacetate, triethylene glycol diacetate, hexanediol diacetate, and 2-methyl-2-propene-1, 1-diol diacetate; glycol esters such as triethylene glycol divalproate, 2, 4-trimethyl-1, 3-pentanediol monoisobutyrate, and 2,2, 4-trimethyl-1, 3-pentanediol diisobutyrate; glycol acrylates such as ethylene glycol diacrylate, diethylene glycol diacrylate, propylene glycol monoacrylate, 2-dimethyl-trimethylene glycol diacrylate and 1, 3-butanediol diacrylate; glycol dinitrates such as ethylene glycol dinitrate, diethylene glycol dinitrate, triethylene glycol dinitrate and propylene glycol dinitrate; 2, 2' - [1, 4-phenylenedioxy ] diethanol; cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose; polyvinylpyrrolidone; carrageenan; polyvinyl butyral; polyethylene glycol; dioxane; butanediol adipate polyester; esters such as isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate and pentaerythritol tetrakis-2-ethylhexanoate; polysaccharides such as dextrin and maltodextrin; lower alcohols such as ethanol and isopropanol; glycol ethers such as 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 monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; water-based base agents such as water.

Among them, preferred are hydrocarbons (particularly, alpha-olefin oligomer, squalane, light liquid paraffin, liquid paraffin), fatty acid triglyceride (particularly, glycerol tri-2-ethylhexanoate, glycerol tri (caprylic/capric acid), higher alcohols (particularly, cetyl alcohol, stearyl alcohol, behenyl alcohol), silicone oils (particularly, methyl polysiloxane, alkyl acrylate copolymer methylpolysiloxane ester, crosslinked methyl polysiloxane, decamethylcyclopentasiloxane, ethyltrisiloxane, methylpolytrimethylsiloxane, methyl siloxane network polymer, polyoxyethylene-methyl polysiloxane copolymer, polymethylhydrosiloxane, triethoxysilylethylpolysiloxyethylhexylpolydimethylsiloxane, dimethylpolysiloxane), esters (particularly, isononyl isononanoate, pentaerythritol tetra-2-ethylhexanoate), Polysaccharides (especially dextrin and maltodextrin), glycol ether (especially diethylene glycol monoethyl ether), and water.

The base or the carrier may be used singly or in combination of two or more.

Additive agent

The composition for external use of the present invention may contain known additives added to cosmetics, for example, antioxidants, surfactants, thickeners, preservatives, pH adjusters, stabilizers, irritation reducing agents, preservatives, colorants, perfumes, pearlizing agents, and the like, within a range that does not impair the effects of the present invention.

Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid derivatives, tocopherol derivatives, isoascorbic acid, and L-cysteine hydrochloride.

Examples of the surfactant include: sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerin sorbitan penta-2-ethylhexanoate, and diglycerin sorbitan tetra2-ethylhexanoate; propylene glycol esters of fatty acids such as propylene glycol monostearate; a glycerol alkyl ether; an alkyl glucoside; amines such as stearylamine and oleylamine; silicone surfactants such as polyoxyethylene methyl polysiloxane copolymer, lauryl PEG-9 dimethiconoethyl dimethicone, and PEG-9 dimethiconoethyl dimethicone.

Examples of the thickener include guar gum, locust bean gum, carrageenan, xanthan gum, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, alkyl acrylate methacrylate copolymer, polyethylene glycol, bentonite, alginic acid, polyethylene glycol (Macrogol), cellulose-based thickener (methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, and the like), and salts thereof.

Examples of the preservative and preservative include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl parahydroxybenzoate, methyl parahydroxybenzoate, phenoxyethanol, benzyl alcohol, chlorobutanol, sorbic acid and its salts, chlorhexidine gluconate, alkanediol, and fatty acid glyceride.

Examples of the pH adjuster include inorganic acids (hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, sodium succinate, etc.), inorganic bases (potassium hydroxide, sodium hydroxide, etc.), organic bases (triethanolamine, diisopropanolamine, triisopropanolamine, etc.), and the like.

Examples of the stabilizer include sodium polyacrylate, dibutylhydroxytoluene, butylhydroxyanisole, and edetate.

Examples of the irritation reducing agent include licorice extract and sodium alginate.

The additives may be used singly or in combination of two or more.

Other effective components

The composition for external use of the present invention may contain other effective components within a range not impairing the effects of the present invention. Specific examples of the active ingredient include a moisturizing ingredient, an anti-inflammatory ingredient, an antibacterial ingredient, vitamins, peptides or derivatives thereof, a cell activating ingredient, an anti-aging ingredient, a blood circulation promoting ingredient, a keratolytic ingredient, a whitening ingredient, an astringent ingredient, and the like.

As the moisture-retaining component, there can be mentioned: high molecular compounds such as collagen, elastin, keratin, chitin, and chitosan; natural moisturizing factors such as sodium lactate, urea, and sodium pyrrolidone carboxylate; lipids such as ceramide, cholesterol, and phospholipid; plant extracts such as chamomile extract, witch hazel extract, tea extract, and perilla extract.

Examples of the anti-inflammatory component include components derived from plants (e.g., daisy), allantoin, glycyrrhizic acid or its derivatives, zinc oxide, pyridoxine hydrochloride, tocopherol acetate, salicylic acid or its derivatives, and aminocaproic acid.

Examples of the antibacterial or bactericidal component include ethanol, chlorhexidine, salicylic acid, benzalkonium chloride, rivanol, sulfur, resorcinol, benzethonium chloride, adapalene, benzoyl peroxide, clindamycin, cresol, gluconic acid and its derivatives, povidone iodine, potassium iodide, iodine, isopropyl methylphenol, triclocarban, triclosan, photosensitizer No. 101, photosensitizer No. 201, paraben, phenoxyethanol, 1, 2-pentanediol, alkyldiaminoglycine hydrochloride, chlorhexidine gluconate, zinc p-phenolsulfonate, and the like.

Examples of vitamins include: retinol derivatives such as retinol, retinol acetate and retinol palmitate, retinol, retinoic acid, methyl retinoic acid, ethyl retinoic acid ester, retinol retinoic acid ester, d-tocopherol retinoic acid ester, α -tocopherol retinoic acid ester, β -tocopherol retinoic acid ester and other vitamin A compounds; vitamin E compounds such as dL-alpha-tocopherol, dL-alpha-tocopherol acetate, dL-alpha-tocopherol succinate, and dL-alpha-tocopherol calcium succinate; vitamin B2 such as riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5' -phosphate sodium, and riboflavin tetranicotinate; nicotinic acids such as DL-alpha-tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, beta-butoxyethyl nicotinate, and 1- (4-methylphenyl) ethyl nicotinate; vitamin C compounds such as ascorbyl pro-A, ascorbyl stearate, ascorbyl palmitate, and dipalmitate L-ascorbate; vitamin D compounds such as hesperidin methyl, ergocalciferol and cholecalciferol; vitamin K, gamma-oryzanol, dibenzoylsulfonamide, and dibenzoylsulfonamide hydrochloride such as phylloquinone and farnesyl quinone; vitamin B1 such as thiamine hydrochloride, thiamine hexadecyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine hydrochloride, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate hydrochloride, thiamine triphosphate monophosphate, and the like; vitamin B6 such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, pyridoxal 5' -phosphate, and pyridoxamine hydrochloride; vitamin B12 such as cyanocobalamin, hydroxycobalamin, and deoxycobalamin; folic acid such as folic acid and pteroylglutamic acid; nicotinic acids such as nicotinic acid and nicotinamide; pantothenic acids such as pantothenic acid, calcium pantothenate, panthenol (panthenol), D-pantetheine (D- パンテサイン), D-pantethine, coenzyme A, and panthenyl ethyl ether; biotin such as biotin and biocytin (ビオチシン); ascorbic acid derivatives such as ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbyl phosphate, and magnesium ascorbyl phosphate; and vitamin-like action factors such as carnitine, ferulic acid, alpha-lipoic acid, orotic acid and the like.

Examples of the peptide or its derivative include a keratinolytic peptide, a hydrolyzed keratin, a collagen, a fish-derived collagen, a atelocollagen, a gelatin, an elastin degradation peptide, a collagen degradation peptide, a hydrolyzed collagen, a hydroxypropylammonium chloride hydrolyzed collagen, an elastin degradation peptide, a conchiolin degradation peptide, a hydrolyzed conchiolin, a fibroin degradation peptide, a hydrolyzed silk, a lauroyl hydrolyzed silk sodium, a soybean protein degradation peptide, a hydrolyzed soybean protein, a wheat protein degradation peptide, a hydrolyzed wheat protein, a casein degradation peptide, and an acylated peptide (e.g., a palmitoyl oligopeptide, a palmitoyl pentapeptide, and a palmitoyl tetrapeptide).

As the cell activating components, there can be mentioned: vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids; α -hydroxy acids such as glycolic acid and lactic acid; tannic acid, flavonoid, saponin, allantoin, and photosensitizer No. 301.

Examples of the anti-aging ingredient include pangamine, kinetin, ursolic acid, curcuma aromatica extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, and mevalonolactone.

Examples of the blood circulation-promoting component include: ingredients derived from plants (e.g., Korean ginseng, Angelica keiskei, Arnica montana, Ginkgo biloba, fennel, Rabdosia amethystoides, Oak, Matricaria chamomilla, Roman chamomilla, carrot, gentian, burdock, rice, hawthorn, shiitake, Crataegus pinnatifida, Juniperus communis, Ligusticum chuanxiong, swertia japonica, thyme, clove, dried orange peel, Angelica sinensis, peach kernel, orange peel, ginseng, garlic, butcher's broom, grape, peony, horse chestnut, melissa, grapefruit, coix seed, rosemary, rose hip, dried orange peel, Angelica sinensis, orange peel, peach, apricot, walnut, corn); glucosyl hesperidin, and the like.

Examples of the keratolytic ingredient include salicylic acid, glycolic acid, tartaric acid, phytic acid, and sulfur.

Examples of the whitening component include ascorbic acid and its derivatives, arbutin, tocopherol, and the like.

Examples of the astringent component include zinc p-phenolsulfonate, zinc oxide, menthol, and ethanol.

The other active ingredients may be used singly or in combination of two or more.

Application method

The method of using the composition for external use of the present invention varies depending on the skin condition, age, nature, and the like of the subject, and the following methods can be employed, for example. That is, an appropriate amount (e.g., about 0.05g to about 5g) may be applied (applied, sprayed, stuck, etc.) to the skin several times a day (e.g., about 1 to 5 times, preferably 1 to 3 times). The composition may be applied so that the amount of the acid mucopolysaccharide used per day is, for example, about 0.00005g to about 0.025 g.

The external composition of the present invention can also be applied to any skin of the face, neck, hand, foot, finger, trunk, scalp, etc.

Use of

The external composition of the present invention can be prepared, for example, as an external composition for moisturizing or for imparting a moist feeling, a swelling feeling, or a firm feeling to the skin.

The sense of tightness refers to the following state: after the preparation applied to the skin is gently spread with a finger or a palm so as to be kneaded into the skin, there is a feeling that the applied preparation remains between the finger and the skin, and there is a feeling of adsorption that the skin applied with the preparation is adsorbed to the finger or palm when the finger or palm from which the preparation is spread is separated from the skin.

The present invention includes a method for moisturizing the skin of a human face, neck, hand, foot, finger, body, scalp, or the like by applying (coating, spraying, sticking, or the like) the external composition of the present invention described above containing (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) hydroxyalkyl urea to the skin of the human face, neck, hand, foot, finger, body, scalp, or the like, and a method for imparting a moist, swollen, or firm feel to the skin. These methods may be non-therapeutic methods.

The method of using the external composition of the present invention in these methods is as described for the external composition of the present invention.

Further, the present invention includes a non-therapeutic use of a combination of (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) hydroxyalkyl urea as a skin moisturizing agent and an agent for imparting a moist feel, a swollen feel, or a firm feel to the skin.

Further, the present invention relates to the use of a combination of (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) hydroxyalkyl urea for producing a skin moisturizer and an agent for imparting a moist feel, a swollen feel, or a firm feel to the skin.

The ingredients, dosage forms and methods of use of these formulations are as described for the topical compositions of the present invention.

Examples

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

Test example 1 (Heat stability test)

(1) Preparation of the composition

The compositions of the examples and comparative examples are shown in tables 1 and 2 below. All the numerical values in tables 1 and 2 represent weight%.

[ Table 1]

[ Table 2]

(2) Test method

(measurement of viscosity)

Compositions of examples and comparative examples having compositions shown in tables 1 and 2 were prepared.

Both of the samples immediately after the preparation and the stored products (samples stored at 60 ℃ C. for one week) of each composition were allowed to stand at 25 ℃. + -. 1 ℃ for 12 hours, and then the viscosity was measured. The viscosity reduction was represented by the relative viscosity of a stored product (stored at 60 ℃ C. for one week) assuming that the viscosity immediately after the preparation was 100%. That is, the relative viscosity of each composition was calculated by the following equation.

Relative viscosity (%)

(viscosity of storage product (60 ℃ C., one week)/viscosity immediately after preparation) × 100

The viscosity measurement conditions are as follows.

The viscosity was measured by using RE85 (eastern industry) according to the test method of "(2) cone-plate rotational viscometer (cone-plate viscometer)" described in japanese pharmacopoeia general test methods viscometry method, 16 th edition, 2 nd method rotational viscometer method. That is, the measurement temperature is an average value of three times of measurements of viscosity per minute up to 3 minutes in the measurement under the condition of 25 ℃. + -. 1 ℃.

Basically, as shown in fig. 1, a sample is placed in a gap of an angle α between a cone 1 and a discoidal plate 2, the cone 1 or the discoidal plate 2 is rotated at a constant angular velocity ω or torque T, the torque or angular velocity applied to the discoidal plate 2 or the cone 1 at a steady state is measured, and the viscosity η of the sample is calculated by the following equation.

η＝100×(3α/2πR3)·(T/ω)

Eta: viscosity (mPas) (Pa.s 103 mPas) of the sample

α: angle (rad) between flat circular plate 2 and cone 1

Pi: circumferential ratio

R: radius of the cone (cm)

T: torque acting on the flat circular plate 2 or the surface of the cone 1 (10-7 N.m)

ω: angular velocity (rad/s)

(feeling of use test)

For the compositions of examples and comparative examples used in the viscosity test of test 1, three panelists dropped 0.5ml of each composition on the inner side of the anterior wrist, spread the composition in the range of 2cm × 2cm, and after 5 minutes, "firm feeling" was evaluated in accordance with the evaluation criteria using the sensory index described below.

5: rather have a "tightness".

4: has 'tightness feeling'.

3: overall, has a "tightness".

2: not so much as to have a "firm feeling".

1: there is no "tightness".

(3) Test results

(measurement of viscosity)

The measurement results of the viscosity are shown in FIGS. 2 to 5.

As is clear from fig. 2 to 5, the compositions of comparative examples 1 to 4 containing sodium hyaluronate and polyoxybutylene polyoxyethylene polyoxypropylene glyceryl ether (3B.O) (8E.O) (5P.O) and containing no hydroxyethyl urea exhibited significant viscosity reduction over time, but the compositions of examples 1 to 6 containing hydroxyethyl urea incorporated therein all exhibited significant viscosity reduction over time.

(feeling of use test)

The results are shown in table 3 below. The changes in "firmness" immediately after production and in the stored products (stored at 60 ℃ C. for one week) were compared, and as a result, the use feeling index of the examples was higher than that of the comparative examples in any case. The effect of suppressing the decrease in the "firm feeling" due to thermal aging was confirmed by the incorporation of hydroxyethyl urea.

[ Table 3]

Test example 2 (light stability test)

(1) Preparation of the composition

The compositions of the examples and comparative examples are shown in table 4 below. All the numerical values in table 4 represent wt%.

[ Table 4]

(2) Test method

(measurement of viscosity)

Each composition of examples and comparative examples having the composition shown in table 4 was prepared.

Each composition was filled in a glass container having a capacity of 30mL, and the viscosity at 25 ℃ was measured as the initial viscosity. Then, SUNTEST XLS + (manufactured by Toyo Seiki Seisaku Co., Ltd.) was used in an amount of 10000kJ/m²Was irradiated with light and then immediately measured for viscosity at 25 ℃.

The viscosity measurement of each of the non-irradiated sample and the irradiated sample was carried out at 25 ℃. + -. 1 ℃. The viscosity measurement conditions were the same as in test example 1. The viscosity reduction was performed by assuming that the viscosity of the sample was 100% and the viscosity after irradiation was represented by the relative viscosity. That is, the relative viscosity of each composition was calculated by the following equation.

Relative viscosity (%) × 100 (viscosity of irradiated sample/viscosity of non-irradiated sample) × 100

(feeling of use test)

For the examples and comparative examples used in the viscosity test of test 2, three panelists dropped 0.5ml of each composition on the inner side of the anterior wrist, spread in the range of 2cm × 2cm, and after 5 minutes, "firming feeling" was evaluated in accordance with the evaluation criteria using the sensory index described below. The method of the feeling in use test was the same as in test example 1.

(3) Test results

(measurement of viscosity)

The results of the viscosity measurement are shown in fig. 6 and 7. As is clear from fig. 6 and 7, the compositions of comparative examples 2 and 5 containing sodium hyaluronate and polyoxybutylene polyoxyethylene polyoxypropylene glyceryl ether (3B.O) (8E.O) (5P.O) and containing no hydroxyethyl urea exhibited significant viscosity reduction with time, but the compositions of examples 7 and 8 containing hydroxyethyl urea incorporated therein exhibited significant viscosity reduction with time.

(feeling of use test)

The results are shown in table 5 below. As a result of comparing the changes in the "tightness" of the ultraviolet-irradiated sample and the non-irradiated sample, the use feeling index of the examples was higher than that of the comparative example in any case. The effect of suppressing the decrease in the "firm feeling" due to thermal aging was confirmed by the incorporation of hydroxyethyl urea.

[ Table 5]

Formulation examples

Specific formulation examples of the external composition of the present invention are shown below. The content of the components in the formulation examples is expressed in "% by weight".

Formulation example 1 cosmetic liquid

Formulation example 2 emulsion

Formulation example 3 gel cream

Formulation example 4 emulsion

The microcapsule containing the organic fluorescent agent is a microcapsule produced by the method described in example 1 of WO 2012/102397.

Formulation example 5 gel cosmetic liquid

The microcapsule containing the organic fluorescent agent is a microcapsule produced by the method described in example 1 of WO 2012/102397.

Formulation example 6 gel cosmetic liquid

The microcapsule containing the organic fluorescent agent is a microcapsule produced by the method described in example 2 of WO 2012/102397.

Formulation example 7 emulsion

The microcapsule containing the organic fluorescent agent is a microcapsule produced by the method described in example 2 of WO 2012/102397.

Formulation example 8 cream

The microcapsule containing the organic fluorescent agent is a microcapsule produced by the method described in example 3 of WO 2012/102397.

Formulation example 9 cream

The microcapsule containing the organic fluorescent agent is a microcapsule produced by the method described in example 4 of WO 2012/102397.

Industrial applicability

The composition for external use of the present invention suppresses a decrease in viscosity of acidic mucopolysaccharides with time, and can maintain a good feeling of use with viscosity for a long period of time. In addition, along with this, the decrease in moisturizing performance and performance of imparting a moist feeling or a firm feeling to the skin is also suppressed. As described above, the composition for external use of the present invention is a product having high commercial value because the properties of the acidic mucopolysaccharides are not deteriorated by distribution and storage.

Claims (15)

1. A composition for external use which comprises (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group and (c) a hydroxyalkyl urea.

2. The composition for external use according to claim 1, wherein the hydroxyalkyl urea is N- (2-hydroxyethyl) urea.

3. The composition for external use according to claim 1 or 2, wherein the acidic mucopolysaccharide is selected from the group consisting of hyaluronic acid and chondroitin sulfate and salts thereof.

4. The composition for external use according to any one of claims 1 to 3, wherein the compound having a polyoxyalkylene group is polyoxybutylene polyoxyethylenepolyoxypropylene glycerin.

5. The composition for external use according to any one of claims 1 to 4, wherein the hydroxyalkyl urea is contained in an amount of 0.0001 to 2000 parts by weight based on 1 part by weight of the polyoxyalkylene-containing compound.

6. The composition for external use according to any one of claims 1 to 5, wherein the hydroxyalkyl urea is contained in an amount of 0.01 to 10000 parts by weight based on 1 part by weight of the acidic mucopolysaccharide.

7. The composition for external use according to any one of claims 1 to 6, wherein the acidic mucopolysaccharide is contained in an amount of 0.000001 to 1 wt% based on the total amount of the composition.

8. The composition for external use according to any one of claims 1 to 7, wherein the hydroxyalkyl urea is contained in an amount of 0.001 to 30% by weight based on the total amount of the composition.

9. The composition for external use according to any one of claims 1 to 8, wherein the polyoxyalkylene-containing compound is contained in an amount of 0.01 to 20% by weight based on the total amount of the composition.

10. The composition for external use according to any one of claims 1 to 9, which is used for moisturizing.

11. The external composition according to any one of claims 1 to 9, which is used for imparting a firm feeling to the skin.

12. A method for moisturizing skin or imparting a moist, swollen or firm feeling to skin by applying to the skin of a human an external composition containing (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) hydroxyalkyl urea.

13. The method of claim 12, which is a non-therapeutic method.

A non-therapeutic use of a combination of (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) a hydroxyalkyl urea as a skin moisturizing agent or an agent for imparting a moist, swollen or firm feel to the skin.

Use of a combination of (a) an acidic mucopolysaccharide, (b) a compound having a polyoxyalkylene group, and (c) a hydroxyalkyl urea, for producing a skin moisturizer or an agent for imparting a moist, swollen or firm feel to the skin.