JP7546341B2 - Composition for external use containing cholesterol and/or phytosterol - Google Patents

Description

The present invention relates to a composition for external use that contains cholesterol and/or phytosterol.

Dry skin, rough skin associated with atopic dermatitis, and dry skin caused by a decrease in the moisture content of the stratum corneum due to aging or a decrease in the skin's barrier function can be very uncomfortable, including causing severe itching, and can interfere with daily life.

Therefore, preventive measures that improve atopic dermatitis, moisturize the skin, maintain the skin's barrier function, and protect the skin from external stimuli are important.

Cholesterols are one of the factors contained in the intercellular lipids present in the stratum corneum, and play an important role in the skin's moisturizing and barrier mechanisms. (Non-Patent Document 1). For this reason, they are incorporated into many cosmetics, quasi-drugs, and pharmaceuticals in the hope of improving atopic dermatitis and dry rough skin. On the other hand, phytosterol is a lipid with a sterol skeleton contained in plants, and is a general term for sterols that have an alkyl group at the 24th position of the steroid skeleton. They are incorporated into topical skin preparations for the purpose of moisturizing effects, improving rough skin, and improving the skin's barrier function. (Patent Documents 1 to 3).

Previously, topical preparations containing high concentrations of cholesterol have been proposed that aim to stabilize the drug by using large amounts of surfactants, phospholipids, polar solvents, etc. (Patent Documents 4 and 5).

JP 2001-2574 A JP 2000-344650 A JP 2001-48728 A JP 2004-59529 A Japanese Patent Application Publication No. 9-124433

Fragrance Journal Special Issue, No. 17, (2000), pp. 20-26

The present invention aims to provide a cholesterol- and/or phytosterol-containing topical composition that has good properties.

Until now, it has been extremely difficult to prepare a formulation that contains high concentrations of cholesterol and/or phytosterols and has a good balance of stability, usability, and ease of use.

As a result of intensive research by the present inventors to solve the above problems, the present invention provides:
(A) cholesterol and/or phytosterol 3% by mass or more;
The present inventors have found that by preparing a topical composition containing (B) a higher alcohol having 12 to 22 carbon atoms and/or a higher fatty acid having 12 to 22 carbon atoms; and (C) 20% by mass or less of a silicone oil, a topical composition that is excellent in usability and stability over a wide temperature range, including low temperatures, can be obtained, and have completed the present invention.

That is, the present invention provides the topical compositions described below.
Item 1.
(A) cholesterol and/or phytosterol 3% by mass or more;
A composition for external use comprising (B) a higher alcohol having 12 to 22 carbon atoms and/or a higher fatty acid having 12 to 22 carbon atoms; and (C) 20% by mass or less of a silicone oil.
Item 2.
Item 2. The composition for external use according to item 1, wherein the component (C) is one or more selected from the group consisting of dimethicone, methylphenylpolysiloxane, and cyclopentasiloxane.
Item 3.
Item 3. The composition for external use according to item 1 or 2, further comprising (D) a polyhydric alcohol.
Item 4.
Item 4. The composition for external use according to any one of Items 1 to 3, wherein the total content of surfactants is 15% by mass or less.
Item 5.
2. The composition for external use according to claim 1, wherein the total content of oily components is 40.1% by mass or less of the total composition.
Item 6.
Item 6. The composition for external use according to any one of Items 1 to 5, which is a composition for external use on the skin to be applied to the skin.
Item 7.
Item 7. The composition for external use according to any one of Items 1 to 6, which is an oil-in-water (O/W) type cream.

Furthermore, the present invention provides the following methods.
Item 8.
(A) cholesterol and/or phytosterol 3% by mass or more;
A method for improving the feel of a topical composition by using in combination (B) at least one selected from higher alcohols having 12 to 22 carbon atoms and/or higher fatty acids having 12 to 22 carbon atoms; and (C) a silicone oil.
Item 9.
Item 9. The method according to item 8, wherein the improvement in the feeling of use is improvement in spreadability.

The present invention provides a composition for external use that is highly stable.

FIG. 1 is a graph showing the evaluation results of the moisture evaporation inhibition of topical compositions of Examples and Comparative Examples. FIG. 2 is an image showing the viscosity suppressing effect of the topical composition of the example. FIG. 3 is a graph showing the relationship between strain and storage modulus and loss modulus for topical compositions of Examples and Comparative Examples. FIG. 4 is a microscope image of the topical composition of the example immediately after production. FIG. 5 is a microscope image of the comparative topical composition immediately after production. FIG. 6 is a microscope image of the comparative example of a topical composition after storage at 4° C. for two weeks. FIG. 7 is a microscope image of the comparative example of a topical composition after storage at 25° C. for two weeks. FIG. 8 is a photograph showing the evaluation results of the vanishing test of the topical compositions of the Examples and Comparative Examples.

In this specification, the unit of content "mass%" is synonymous with "g/100g."

The composition for external use of the present invention contains: (A) 3% by mass or more of cholesterol and/or phytosterol;
The composition for external use contains (B) a higher alcohol having 12 to 22 carbon atoms and/or a higher fatty acid having 12 to 22 carbon atoms; and (C) 20% by mass or less of a silicone oil.

Cholesterol or phytosterol is a poorly soluble lipid, so it is difficult to incorporate it into a formulation. That is, it is expected to have a high effect on rough skin such as atopic dermatitis, rough skin, and improvement of barrier function, but in order to expect the effect of cholesterol or phytosterol, a large amount of solvent is required to incorporate it at a high concentration. On the other hand, if the amount of solvent or stabilizer is reduced in order to solve these problems, the formulation becomes unstable and there is a concern about stability problems such as crystal precipitation, so it is very difficult to achieve both stability and usability in a formulation containing cholesterol and/or phytosterol at a high concentration. Furthermore, cholesterol or phytosterol is a solid oil, and due to its characteristics, the viscosity, viscosity or hardness of the formulation increases as the formulation is incorporated at a high concentration, so there is a problem that the usability and usability are deteriorated, such as difficulty in spreading when used, and further, it has been found that when the formulation is contained in a container such as a tube container, it becomes difficult to eject the formulation when used, and the usability itself as an external agent is deteriorated.
For these reasons, it has been extremely difficult to prepare a preparation that contains cholesterol or phytosterol at a concentration that is expected to be highly effective against atopic dermatitis, rough skin, and improving barrier function, while also providing a satisfactory feel and ease of use.

The term "usability" in the present invention refers to a concept including usability such as skin affinity, a good feel with little stickiness, and ease of application, and may also refer to high handleability that allows for frequent care. In other words, in this specification, "good usability" refers to having any of the above advantages. According to the present invention, for example, even when contained in a container such as a tube that is convenient to carry, it has a moderate hardness that makes it easy to take out of the tube, and it is possible to achieve remarkable convenience.

[(A) Cholesterol and/or Phytosterol]
Both cholesterol and phytosterol contained in the topical composition of the present invention are compounds belonging to sterols. Cholesterol is a sterol compound that is a poorly soluble lipid with a melting point of 140°C or higher. Phytosterol is a general term for a series of sterol compounds originating from plants, which have an alkyl group at the 24th position of the steroid skeleton. Phytosterols include sterols such as β-sitosterol, campesterol, stigmasterol, and brassicasterol. In this specification, the term "phytosterol" may refer to any one or a combination of two or more compounds belonging to the phytosterol category.

In the present invention, cholesterol and/or phytosterols that are commercially available in the fields of pharmaceuticals, quasi-drugs, or cosmetics, for example as ingredients of skin care products, can be used. Commercially available products include Cholesterol NF (Croda Co., Ltd.) official cholesterol, Presome CS2-101, Phytopresome, etc. (Nippon Fine Chemical Co., Ltd.), Phytosterol (Eisai Food Chemicals), and Phytosterol S (Tama Biochemical Co., Ltd.).

In the present invention, cholesterol or phytosterols can be used alone or in combination of two or more.

In the topical composition of the present invention, the total content of the component (A) relative to the total amount of the topical composition is appropriately set depending on the balance with other components. The total content of the component (A) relative to the total amount of the topical composition is not particularly limited as long as it is 3% by mass or more from the viewpoint of exerting its effect, but is preferably 20% by mass or less, more preferably 15% by mass or less, and even more preferably 10% by mass or less. The total content of the component (A) relative to the total amount of the topical composition is 3% by mass or more. In some cases, the content of the component (A) can be 3.5% by mass or more, or even 4% by mass or more. The total content of the component (A) relative to the total amount of the topical composition is preferably 3% by mass to 20% by mass, more preferably 3% by mass to 15% by mass, and even more preferably 3% by mass to 10% by mass.

[(B) Higher alcohol having 12 to 22 carbon atoms and/or higher fatty acid having 12 to 22 carbon atoms]
(Higher alcohols having 12 to 22 carbon atoms)
The higher alcohol having 12 to 22 carbon atoms contained in the topical composition of the present invention is not particularly limited as long as it is used in the fields of medicines, quasi-drugs, or cosmetics, for example, as a component of a skin topical agent. As the higher alcohol, a higher alcohol having 12 to 22 carbon atoms is preferable, a higher alcohol having 14 to 22 carbon atoms is more preferable, and a higher alcohol having 16 to 22 carbon atoms is even more preferable.

The higher alcohol having 12 to 22 carbon atoms is not limited, but preferably includes linear saturated alcohols (solid at room temperature) such as lauryl alcohol, myristyl alcohol, cetanol, cetostearyl alcohol, stearyl alcohol, arachyl alcohol, and behenyl alcohol; unsaturated alcohols (liquid at room temperature) such as oleyl alcohol and selachyl alcohol; or branched alcohols (liquid at room temperature) such as hexyldecanol, isostearyl alcohol, octyldodecanol, decyltetradecanol, lanolin alcohol, and isostearyl glyceryl ether. In the present invention, although not limited, linear saturated alcohols or branched alcohols are particularly preferred, and of these, linear saturated alcohols are more preferred. Among these, from the viewpoint of compatibility with component (A) and stability, lauryl alcohol, myristyl alcohol, cetanol, cetostearyl alcohol, stearyl alcohol, arachyl alcohol, behenyl alcohol, hexyldecanol, isostearyl alcohol, octyldodecanol, decyltetradecanol, lanolin alcohol, and isostearyl glyceryl ether are particularly preferred, lauryl alcohol, myristyl alcohol, cetanol, cetostearyl alcohol, stearyl alcohol, arachyl alcohol, behenyl alcohol, isostearyl alcohol, and octyldodecanol are even more particularly preferred, and cetanol, cetostearyl alcohol, stearyl alcohol, and behenyl alcohol are even more particularly preferred. In the present invention, the higher alcohols having 12 to 22 carbon atoms can be used alone or in combination of two or more kinds.

(Higher fatty acids with 12 to 22 carbon atoms)
The higher fatty acid having 12 to 22 carbon atoms that can be contained in the topical composition of the present invention is not particularly limited as long as it is used in the fields of pharmaceuticals, quasi-drugs, or cosmetics, for example, as a component of a skin topical agent. As the higher fatty acid, a higher fatty acid having 12 to 22 carbon atoms is preferable, a higher fatty acid having 14 to 22 carbon atoms is more preferable, and a higher fatty acid having 16 to 22 carbon atoms is even more preferable.

The higher fatty acid having 12 to 22 carbon atoms is not limited, but preferably includes linear saturated fatty acids (solid at room temperature) such as lauric acid, myristic acid, palmitic acid, stearic acid, margaric acid, arachidonic acid, or behenic acid; unsaturated fatty acids (liquid at room temperature) such as oleic acid, linoleic acid, linolenic acid, arachidonic acid, palmitoleic acid, eicosapentaenoic acid, paccenic acid, or docosahexaenoic acid; or branched fatty acids such as isostearic acid or lanolin fatty acid, or 12-hydroxystearic acid. In the present invention, linear saturated fatty acids are particularly preferred, although not limited thereto. Among these, from the viewpoint of compatibility with component (A) and stability, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, or behenic acid is preferred, isostearic acid, myristic acid, palmitic acid, stearic acid, and behenic acid are more preferred, and palmitic acid, stearic acid, and behenic acid are even more preferred. In the present invention, the higher fatty acids having 12 to 22 carbon atoms can be used alone or in combination of two or more.

In the topical composition of the present invention, at least one type of higher alcohol having 12 to 22 carbon atoms or at least one type of higher fatty acid having 12 to 22 carbon atoms can be used as component (B), and it is also possible to use both of them. Lauryl alcohol, myristyl alcohol, cetanol, cetostearyl alcohol, stearyl alcohol, arachyl alcohol, behenyl alcohol, hexyldecanol, isostearyl alcohol, octyldodecanol, decyltetradecanol, lanolin alcohol, isostearyl glyceryl ether, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, and behenic acid are preferred, myristyl alcohol, cetanol, cetostearyl alcohol, stearyl alcohol, arachyl alcohol, or behenyl alcohol, isostearyl alcohol, octyldodecanol, isostearic acid, myristic acid, palmitic acid, stearic acid, and behenic acid are more preferred, and cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, palmitic acid, stearic acid, and behenic acid are even more preferred.

By using such component (B), it is possible to suppress an increase in the viscosity or hardness of the formulation even when cholesterol or phytosterol is blended at a high concentration, and it is possible to achieve both a good feel and ease of use.

In the topical composition of the present invention, the total content of the (B) component relative to the total amount of the topical composition is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, even more preferably 0.5% by mass or more, and even more preferably 1% by mass or more. The total content of the (B) component relative to the total amount of the topical composition is preferably 30% by mass or less, more preferably 20% by mass or less, even more preferably 15% by mass or less, even more preferably 10% by mass or less, and most preferably 8% by mass or less.

The total content of component (B) relative to the total amount of the topical composition is preferably 0.01 to 30% by mass, more preferably 0.1 to 20% by mass, even more preferably 0.5 to 15% by mass, even more preferably 1 to 10% by mass, and most preferably 1 to 8% by mass.

In the topical composition of the present invention, the ratio of the content of component (B) to component (A) is not particularly limited, but is preferably 0.001 to 6 parts by mass, more preferably 0.01 to 5 parts by mass, and even more preferably 0.05 to 3 parts by mass, per 1 part by mass of the total content of component (A).

[(C) Silicone oil]
The silicone oil used in the present invention is not particularly limited as long as it is used in the fields of medicines, quasi-drugs, or cosmetics, for example as a component of external skin preparations. The silicone oil is not limited, but preferred examples thereof include silicone oils such as methylpolysiloxane, methylphenylpolysiloxane, decamethylcyclopentasiloxane, methylcyclopentasiloxane, highly polymerized methylpolysiloxane, decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane, methylhydrogenpolysiloxane, methyltrimethicone, dimethiconol, dimethiconol crosspolymer, and other siloxanes, alkyl-modified silicones such as caprylyl methicone, amino-modified silicones such as aminopropyl dimethicone and amodimethicone, crosslinked methylpolysiloxane, crosslinked alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-modified silicone, crosslinked polyether-modified silicone, crosslinked alkyl polyether-modified silicone, silicone/alkyl chain co-modified polyether-modified silicone, silicone/alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, phenyl-modified silicone, and silicone resin. Among these, methylpolysiloxane, methylphenylpolysiloxane, decamethylcyclopentasiloxane, methylcyclopentasiloxane, high-polymerized methylpolysiloxane, or octamethylcyclotetrasiloxane is particularly preferred, and methylpolysiloxane, methylphenylpolysiloxane, decamethylcyclopentasiloxane, methylcyclopentasiloxane, high-polymerized methylpolysiloxane are particularly preferred. In the present invention, the silicone oil can be used alone or in combination of two or more. By including silicone oil, foaming or white residue can be prevented, and a stop feeling can be prevented when applied to the skin. By including silicone oil, good spreading, reduced friction, and improved smoothness can be expected. If the content of silicone oil exceeds 20% by mass, the feel specific to silicone will be too prominent, and the feeling of use may worsen.

In the topical composition of the present invention, the total content of the (C) component relative to the total amount of the topical composition is 20% by mass or less, preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 8% by mass or less, even more preferably 5% by mass or less, and most preferably 3% by mass or less. The total content of the (C) component relative to the total amount of the topical composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, even more preferably 0.1% by mass or more, and most preferably 0.5% by mass or more.

The total content of component (C) relative to the total amount of the topical composition is preferably 0.01 to 20% by mass, more preferably 0.05 to 15% by mass, even more preferably 0.05 to 10% by mass, even more preferably 0.1 to 5% by mass, and most preferably 0.5 to 3% by mass.

In the topical composition of the present invention, the ratio of the content of component (C) to component (A) is not particularly limited, but is preferably 0.0006 to 7 parts by mass, more preferably 0.001 to 5 parts by mass, even more preferably 0.05 to 5 parts by mass, even more preferably 0.01 to 3 parts by mass, and most preferably 0.1 to 3% by mass, per 1 part by mass of the total content of component (A).

[Polyhydric alcohol]
The topical composition of the present invention may contain a polyhydric alcohol in addition to the above-mentioned (A), (B) and (C) components, so long as the effect of the present invention is not hindered from the viewpoint of improving the feeling of use, stability, etc. The polyhydric alcohol used in the present invention is not particularly limited as long as it is used, for example, as a component of a skin topical agent in the fields of medicines, quasi-drugs or cosmetics. The polyhydric alcohol is not limited, but is preferably at least one selected from the group consisting of diethylene glycol, polyethylene glycol (PEG), propylene glycol (PG), butylene glycol (BG), dipropylene glycol (DPG), glycerin, diglycerin, isoprene glycol, diethylene glycol, ethoxydiglycol, polypropylene glycol, polyglycerin, pentanediol, octanediol or hexanediol.

In the topical composition of the present invention, the total content of polyhydric alcohols relative to the total amount of the topical composition is preferably 30% by mass or less, more preferably 25% by mass or less, even more preferably 20% by mass or less, even more preferably 15% by mass or less, and most preferably 10% by mass or less.

The total content of polyhydric alcohols in the total amount of the topical composition is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, even more preferably 1% by mass or more, even more preferably 3% by mass or more, and most preferably 5% by mass or more.

The total content of polyhydric alcohols in the total amount of the topical composition is preferably 0.1 to 30% by mass, more preferably 0.5 to 30% by mass, even more preferably 1 to 25% by mass, even more preferably 3 to 20% by mass, and most preferably 5 to 15% by mass.

In the topical composition of the present invention, the ratio of the content of the polyhydric alcohol to the content of component (A) is not particularly limited, but is preferably 0.001 to 10 parts by mass, more preferably 0.05 to 10 parts by mass, and even more preferably 0.1 to 5 parts by mass, per 1 part by mass of the total content of component (A).

[Surfactants]
The topical composition of the present invention may contain a surfactant in addition to the above-mentioned (A), (B) and (C) components, so long as the effect of the present invention is not hindered, from the viewpoint of improving the feeling of use, stability, etc. The surfactant contained in the topical composition of the present invention is not particularly limited as long as it is used in the fields of medicines, quasi-drugs or cosmetics, for example, as a component of a skin topical agent. The surfactant is not limited, but the surfactant used here may be any of nonionic surfactants, anionic surfactants, cationic surfactants and amphoteric surfactants.

Among these, examples of nonionic surfactants include POE-branched alkyl ethers such as polyoxyethylene (POE)-octyldodecyl alcohol and POE-2-decyltetradecyl alcohol; POE-alkyl ethers such as POE-oleyl alcohol ether and POE-cetyl alcohol ether; sorbitan fatty acid esters such as sorbitan monooleate, sorbitan monoisostearate, and sorbitan monolaurate; POE-sorbitan fatty acid esters such as POE-sorbitan monooleate, POE-sorbitan monoisostearate, POE-sorbitan monostearate, and POE-sorbitan monolaurate; glycerin monooleate, glycerin monostearate, and glycerin monostearate. Glycerin fatty acid esters such as lycerin monomyristate; POE-glycerin fatty acid esters such as POE-glycerin monooleate, POE-glycerin monostearate, and POE-glycerin monomyristate; POE-dihydrocholesterol ester, POE-hydrogenated castor oil (e.g., polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), polyoxyethylene hydrogenated castor oil 80, etc.); POE castor oils such as POE-castor oil (POE (3) castor oil, POE (20) castor oil, etc.); POE-hydrogenated castor oils such as POE-hydrogenated castor oil isostearate, etc. Oil fatty acid esters; POE alkylaryl ethers such as POE octylphenyl ether; POP and POE alkyl ethers such as POP and POE butyl ether; glycerin alkyl ethers such as monoisostearyl glyceryl ether and monomyristyl glyceryl ether; POE glycerin alkyl ethers such as POE monostearyl glyceryl ether and POE monomyristyl glyceryl ether; POE fatty acid esters such as polyoxyl stearate; POE sterols and hydrogenated sterols such as POE (20) phytosterol, POE (30) phytosterol, POE (25) phytostanol, and POE (30) cholestanol; sucrose caprylic acid ester, sucrose caprylate, etc. Examples of nonionic surfactants include sucrose fatty acid esters such as sucrose laurate, sucrose myristic acid ester, sucrose palmitate, sucrose stearate, sucrose oleate, sucrose isostearate, sucrose linoleate, sucrose linolenate, sucrose coconut oil fatty acid ester, sucrose behenate, and sucrose erucate; polyethylene glycol fatty acid esters such as polyethylene glycol dioleate; and polyglycerin fatty acid esters such as alkyl polyglycosides, diglyceryl monostearate, decaglyceryl decastearate, decaglyceryl decastearate, and diglyceryl diisostearate.

Among these, examples of anionic surfactants include higher alkyl sulfate ester salts (e.g., sodium lauryl sulfate, potassium lauryl sulfate, etc.); alkyl ether sulfate ester salts (e.g., POE-lauryl triethanolamine sulfate, sodium POE-lauryl sulfate, etc.); N-acylsarcosinic acid (e.g., sodium lauroyl sarcosinate, etc.); higher fatty acid amide sulfonates (e.g., sodium N-stearoyl-N-methyl taurine, sodium N-myristoyl-N-methyl taurine, sodium coconut oil fatty acid methyl tauride, sodium lauryl methyl tauride, etc.); phosphate esters and their salts (sodium POE-oleyl ether phosphate, POE-stearyl ether phosphate, potassium cetyl phosphate, cetyl phosphate, etc.); sulfosuccinates (e.g., sodium di-2-ethylhexyl sulfosuccinate, sodium monolauroyl monoethanolamide polyoxyethylene sulfosuccinate, sodium lauryl polypropylene glycol sulfonate, sodium lauro ... anionic surfactants such as sodium succinate, alkylbenzene sulfonate (e.g., sodium linear dodecylbenzene sulfonate, triethanolamine linear dodecylbenzene sulfonate, linear dodecylbenzene sulfonic acid, etc.); higher fatty acid ester sulfate (e.g., sodium hydrogenated coconut oil fatty acid glycerin sulfate, etc.); N-acyl glutamate (e.g., monosodium N-lauroyl glutamate, disodium N-stearoyl glutamate, monosodium N-myristoyl-L-glutamate, etc.); sulfated oil (e.g., turmeric oil, etc.); POE-alkyl ether carboxylic acid; POE-alkyl allyl ether carboxylate; α-olefin sulfonate; higher fatty acid ester sulfonate; secondary alcohol sulfate; higher fatty acid alkylolamide sulfate; sodium lauroyl monoethanolamide succinate; ditriethanolamine N-palmitoyl aspartate; and sodium caseinate.

Among these, examples of cationic surfactants include cationic surfactants such as mono- or di-long-chain alkyl tertiary or quaternary ammonium salts having a linear or branched long-chain alkyl group, which may have an alkylene oxide added thereto.

Among these, examples of amphoteric surfactants include carbobetaine, sulfobetaine, imidazolinium betaine, and amidobetaine.

Other examples include naturally occurring surfactants such as lecithin, hydrogenated lecithin, saponin, sodium surfactin, and bile acid.

These surfactants may be used alone or in any combination of two or more.

Among the above surfactants, in particular, POE-alkyl ethers such as POE-oleyl alcohol ether, POE-cetyl alcohol ether, POE-stearyl alcohol ether, and POE-cetostearyl alcohol ether; sorbitan fatty acid esters such as sorbitan monooleate, sorbitan monoisostearate, and sorbitan monostearate; POE-sorbitan fatty acid esters such as POE-sorbitan monooleate, POE-sorbitan monoisostearate, POE-sorbitan monostearate, and POE-sorbitan monolaurate; glycerin fatty acid esters such as glycerin monooleate, glycerin monostearate, and glycerin monomyristate; POE-glycerin monooleate, POE-glycerin monostearate, and POE-glycerin monostearate; One or more of the following are preferred: serine fatty acid esters; POE-hydrogenated castor oil; POP-POE alkyl ethers such as POP-POE-butyl ether; glycerin alkyl ethers such as monoisostearyl glyceryl ether; POE-glycerin alkyl ethers such as POE-monostearyl glyceryl ether; POE fatty acid esters such as polyoxyl stearate; POE sterols and hydrogenated sterols such as POE (20) phytosterol, POE (30) phytosterol, POE (25) phytostanol, and POE (30) cholestanol; sucrose fatty acid esters; polyoxyalkylene alkyl (or alkenyl) ether sulfates, ether carboxylates, alkyl phosphate esters, N-acyl amino acid salts, and acylated taurates; and lecithin.

In the topical composition of the present invention, the content of the surfactant relative to the total amount of the topical composition is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 8% by mass or less, even more preferably 5% by mass or less, and most preferably 3% by mass or less. In the topical composition of the present invention, the content of the surfactant relative to the total amount of the topical composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, even more preferably 0.1% by mass or more, and even more preferably 0.5% by mass or more.

The total surfactant content is preferably 0.01 to 15% by mass, more preferably 0.01 to 10% by mass, even more preferably 0.05 to 8% by mass, even more preferably 0.05 to 5% by mass, and most preferably 0.1 to 3% by mass.

In the topical composition of the present invention, the content ratio of the surfactant to the component (A) is preferably 0.001 to 5 parts by mass, and more preferably 0.001 to 3 parts by mass, per 1 part by mass of the total content of the component (A).

[Oil content]
The topical composition of the present invention may contain oils in addition to the cholesterol and/or phytosterol (A), the higher alcohol and/or higher fatty acid (B), and the silicone oil (C). The other oils include, but are not limited to, those that function as bases or carriers. In addition to the components (A), (B), and (C), examples of the oils that can be used in the present invention include hydrocarbons such as paraffin, ceresin, isoparaffin, hard fat, microcrystalline wax, polybutene, polyethylene powder, liquid paraffin, squalane, petrolatum, gelled hydrocarbons (such as Plastibase), ozokerite, α-olefin oligomers, light liquid paraffin, and light liquid paraffin; isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, isopropyl isostearate, octyl palmitate, octyl isopalmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, isodecyl oleate, hexyldecyl dimethyloctanoate, diisopropyl sebacate, di-2-ethylhexyl sebacate, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, and 2-hexyldecyl palmitate. , diisopropyl adipate, 2-hexyldecyl adipate, isononyl isononanoate, isotridecyl isononanoate, cetyl lactate, myristyl lactate, lanolin acetate, isocetyl stearate, isocetyl isostearate, isostearyl isostearate, cholesteryl 12-hydroxystearate, cholesteryl stearate, cholesteryl oleate, phytosteryl macadamiate, phytosteryl oleate, palmitate, Dextrin phosphate, inulin stearate, hydrogenated jojoba oil, ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid ester, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate, diisostearyl malate, glycerin di-2-heptylundecanoate, tri-2-ethylhexyl trimellitate, tritridecyl trimellitate, tri-2-ethylhexyl trimethylolpropane, tri Trimethylolpropane isostearate, pentaerythritol tetra-2-ethylhexanoate, glycerin tri-2-ethylhexanoate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, glycerin trimyristate, caprylic/capric triglyceride, caprylic/capric/myristic/stearic triglyceride, tri-2-heptylundecanoic acid glyceride, castor oil fatty acid Methyl ester, oleyl oleate, 2-heptyl undecyl palmitate, diisobutyl adipate, di(phytosteryl/octyldodecyl) lauroyl glutamate, di(octyldodecyl/phytosteryl/behenyl) lauroyl glutamate, di-2-heptyl undecyl adipate, ethyl laurate, bisethoxydiglycol cyclohexane-1,4-dicarboxylate, 2-ethylhexyl succinate, ethyl acetate, butyl acetate, acetic acid Ester oils such as amyl, triethyl citrate, dimer dilinoleate (phytosteryl/isostearyl/cetyl/stearyl/behenyl), polyglyceryl-2 triisostearate, dimer dilinoleyl dimer dilinoleate, dipentaerythrityl tripolyhydroxystearate, and tri(behenic acid/isostearic acid/eicosane diacid)glyceryl; avocado oil, linseed oil, camellia oil, macadamia nut oil, corn oil, and olive oil. Examples of oils and fats include safflower oil, apricot kernel oil, cinnamon oil, jojoba oil, grape seed oil, sunflower oil, almond oil, camellia oil, rapeseed oil, sesame oil, cocoa butter, coconut oil, hardened coconut oil, palm oil, palm kernel oil, Japan wax kernel oil, Japan wax, wheat germ oil, rice germ oil, rice bran oil, cottonseed oil, soybean oil, peanut oil, tea seed oil, and evening primrose oil; and waxes such as candelilla wax, rice bran wax, cotton wax, carnauba wax, lanolin, shellac wax, and beeswax.

Among these, hydrocarbons such as paraffin, isoparaffin, microcrystalline wax, polybutene, polyethylene powder, liquid paraffin, squalane, petrolatum, α-olefin oligomer, light liquid paraffin and light liquid paraffin; isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, isopropyl isostearate, octyl palmitate, octyl isopalmitate, myristyl myristate, diisopropyl adipate, 2-hexyldecyl adipate, Diisopropyl sebacate, isononyl isononanoate, isotridecyl isononanoate, cetyl lactate, isocetyl stearate, isostearyl isostearate, cholesteryl 12-hydroxystearate, cholesteryl stearate, cholesteryl oleate, phytosteryl macadamiate, phytosteryl oleate, dextrin palmitate, inulin stearate, hydrogenated jojoba oil, dipentaerythritol fatty acid ester, neopentyl glycol dicaprate, diisomalate Stearyl, Tri-2-ethylhexyl trimellitate, Tritridecyl trimellitate, Pentaerythritol tetra-2-ethylhexanoate, Glyceryl tri-2-ethylhexanoate, Trimethylolpropane triisostearate, Caprylic/capric triglyceride, Caprylic/capric/myristic/stearic triglyceride, Oleyl oleate, Phytosteryl/octyldodecyl lauroyl glutamate, Octyldodecyl/phytosteryl lauroyl glutamate Preferred are ester oils such as phytosteryl/isostearyl/cetyl/stearyl/behenyl), 2-ethylhexyl succinate, triethyl citrate, and dimer dilinoleic acid (phytosteryl/isostearyl/cetyl/stearyl/behenyl); fats and oils such as avocado oil, camellia oil, macadamia nut oil, corn oil, olive oil, jojoba oil, grape seed oil, sunflower oil, almond oil, sesame oil, cacao butter, rice germ oil, rice bran oil, soybean oil, peanut oil, and evening primrose oil; and waxes such as candelilla wax, rice bran wax, carnauba wax, lanolin, and beeswax. Further, hydrocarbons such as paraffin, isoparaffin, liquid paraffin, squalane, petrolatum, α-olefin oligomers, and light liquid paraffin; isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, isopropyl isostearate, octyl palmitate, diisopropyl adipate, diisopropyl sebacate, isononyl isononanoate, isotridecyl isononanoate, cetyl lactate, isostearyl isostearate, cholesteryl 12-hydroxystearate, cholesteryl oleate, phytosteryl macadamiate, phytosteryl oleate, dextrin palmitate, inulin stearate, hydrogenated jojoba oil, dipentaerythritol fatty acid esters, neopentyl glycol dicaprate, bisethoxy diglycol cyclohexane-1,4-dicarboxylate, , Tri-2-ethylhexyl trimellitate, Tetra-2-ethylhexanoate Pentanerythritol, Tri-2-ethylhexanoate Glycerin, Tri(caprylic acid/capric acid)glyceryl, Tri(caprylic acid/capric acid/myristic acid/stearic acid)glyceryl, Di(phytosteryl/octyldodecyl) lauroyl glutamate, Di(octyldodecyl/phytosteryl/behenyl) lauroyl glutamate, Preferred are ester oils such as 2-ethylhexyl succinate, triethyl citrate, and dimer dilinoleic acid (phytosteryl/isostearyl/cetyl/stearyl/behenyl); oils and fats such as avocado oil, macadamia nut oil, corn oil, olive oil, jojoba oil, grape seed oil, sunflower oil, almond oil, sesame oil, cacao butter, soybean oil, peanut oil, and evening primrose oil; and waxes such as candelilla wax, carnauba wax, and beeswax.
The oils may be used alone or in combination of two or more.

The total content of oils contained in the topical composition of the present invention is preferably 40% by mass or less, including components (A), (B), (C), and other oils. The total content of oils contained in the topical composition of the present invention is preferably 40% by mass or less, more preferably 35% by mass or less, and even more preferably 30% by mass or less. The total content of oils contained in the topical composition of the present invention is preferably 3.02% by mass or more, more preferably 3.2% by mass or more, and even more preferably 4% by mass or more.

[Oily ingredients]
In this specification, "oil component" means oil and surfactant. The total content of oil components contained in the topical composition of the present invention is preferably 40.1 mass% or less from the viewpoint of ensuring the feeling of use and reducing irritation. The total content of oil components contained in the topical composition of the present invention is preferably 40.1 mass% or less, more preferably 40 mass% or less, and even more preferably 35 mass% or less. The total content of oil components contained in the topical composition of the present invention is preferably 3.02 mass% or more, more preferably 3.2 mass% or more, and even more preferably 4 mass% or more.

[Base or carrier]
Examples of bases or carriers include cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose; polyvinylpyrrolidone; carrageenan; polyvinyl butyrate; polyethylene glycol; polysaccharides such as dextrin and maltodextrin; 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; lower alcohols such as ethanol and isopropanol; and the like.

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

[Additives]
The topical composition of the present invention may contain known additives that are added to pharmaceuticals, quasi-drugs, or cosmetics, such as antioxidants, thickeners, preservatives, pH adjusters, stabilizers, irritation reducers, preservatives, colorants, fragrances, and/or pearlescent luster imparting agents, within the scope of not impairing the effects of the present invention.

Examples of antioxidants include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, ascorbic acid derivatives, tocopherol, tocopherol derivatives, erythorbic acid, and L-cysteine hydrochloride.

Examples of thickening agents include guar gum, locust bean gum, carrageenan, xanthan gum, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, acrylates/methacrylates alkyl copolymers, polyethylene glycol, bentonite, alginic acid, macrogol, sodium chondroitin sulfate, and cellulose-based thickening agents such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and carboxyethylcellulose.

Examples of preservatives 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, and alkanediols.

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

The stabilizer may, for example, be sodium polyacrylate, dibutylhydroxytoluene, or butylhydroxyanisole.
Irritation reducers include, for example, licorice extract and sodium alginate.

Additives can be used alone or in combination of two or more.

(Other active ingredients)
The topical composition of the present invention may contain other active ingredients within the scope of not impairing the effects of the present invention. Specific examples of active ingredients include local anesthetic ingredients, antipruritic ingredients, anti-inflammatory and analgesic ingredients, cooling ingredients, moisturizing ingredients, anti-inflammatory ingredients, antibacterial or bactericidal ingredients, vitamins, amino acids or derivatives thereof, cell activating ingredients, anti-aging ingredients, blood circulation promoting ingredients, keratin softening ingredients, whitening ingredients, and astringent ingredients.

Examples of local anesthetic components include lidocaine or a derivative thereof, dibucaine or a derivative thereof, ethyl aminobenzoate, eucalyptus oil, eugenol, camphor, menthol, peppermint oil, and chlorobutanol.
Examples of antipruritic ingredients include crotamiton, chlorpheniramine or a derivative thereof, diphenhydramine or a derivative thereof, salicylic acid, vanillylamide nonylate, mequitazine, camphor, thymol, eugenol, polyoxyethylene lauryl ether, comfrey extract, and perilla extract.
Examples of the anti-inflammatory and analgesic ingredients include indomethacin, felbinac, salicylic acids such as methyl salicylate and glycol salicylate, allantoin or a derivative thereof, ibuprofen, ibuprofen piconol, bufexamac, butyl flufenamate, bendazac, piroxicam, and ketoprofen.
Examples of the cooling component include monoterpenes such as camphor, menthol, borneol, eugenol, cineol, thymol, bisabolol, α-pinene, and limonene; sesquiterpenes such as farnesol and nerolidol; diterpenes such as phytol and cembrene; and essential oils such as eucalyptus oil, peppermint oil, clove oil, cinnamon oil, peppermint oil, mint oil, tea tree oil, chamomile oil, rosemary oil, lemon oil, orange oil, thyme oil, sage oil, and clove oil.

Moisturizing ingredients include, for example, polymeric compounds or hydrolysates thereof such as sodium hyaluronate, heparinoids, sodium chondroitin sulfate, collagen, elastin, keratin, chitin, and chitosan; amino acids such as glycine, aspartic acid, and arginine; natural moisturizing factors such as sodium lactate, urea, and sodium pyrrolidone carboxylate; lipids such as ceramides and phospholipids; polymers having phospholipid polar groups such as MPC polymers (e.g., LIPIDURE (trademark), etc.); polyoxypropylene methylglucoside; PPG-10 methylglucose (e.g., Macbiobride, MG (trademark) series (manufactured by NOF Corporation), etc.), PEG/PPG/polybutylene glycol-8/5/3 glycerin (for example, Wilbride (trademark) S-753 (manufactured by NOF Corporation)); trimethylglycine (betaine); hydroxyethyl urea; acrylic acid/acrylamide/dimethyl diallyl ammonium chloride copolymer; as well as plant extracts such as pearl barley seed extract, artemisia leaf extract, chamomile extract, witch hazel extract, birch sap, glasswort extract, lilac extract, tea extract, lavender oil, and perilla extract; and animal extracts such as placenta extract.

Anti-inflammatory ingredients include, for example, ingredients derived from plants (e.g., comfrey), allantoin, glycyrrhizic acid or its derivatives, glycyrrhetinic acid or its derivatives, zinc oxide, pyridoxine hydrochloride, tocopherol acetate, salicylic acid or its derivatives, azulene, steroids, and ε-aminocaproic acid.

Examples of antibacterial or germicidal ingredients include chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, sulfur, resorcinol, ethanol, benzethonium chloride, adapalene, benzoyl peroxide, clindamycin, cresol, gluconic acid and its derivatives, povidone-iodine, potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer No. 101, photosensitizer No. 201, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiaminoglycine hydrochloride, chlorhexidine gluconate, zinc paraphenolsulfonate, picroton olamine, and miconazole.

Examples of vitamins include vitamin A derivatives such as retinol derivatives (retinol, retinol acetate, retinol palmitate, etc.), retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinol retinoic acid, d-δ-tocopheryl retinoate, α-tocopheryl retinoate, and β-tocopheryl retinoate; vitamin E derivatives such as dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, and dl-α-tocopherol calcium succinate; riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-phosphate, riboflavin ... vitamin B2 such as sodium nicotinate and riboflavin tetranicotinate; nicotinic acids such as dl-α-tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate and 1-(4-methylphenyl)ethyl nicotinate; vitamin C such as ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbyl glucoside, ethyl ascorbate, ascorbyl stearate, ascorbyl palmitate, ascorbyl tetraisopalmitate and L-ascorbyl dipalmitate; Vitamin D such as tylhesperidin, ergocalciferol, and cholecalciferol; Vitamin K such as phylloquinone and farnoquinone; γ-oryzanol, dibenzoylthiamine, and dibenzoylthiamine hydrochloride; Vitamin B1 such as thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, and thiamine triphosphate monophosphate; pyridoxine hydrochloride, pyridoxy acetate, etc. Vitamin B6 such as pyridoxal hydrochloride, pyridoxal 5'-phosphate, and pyridoxamine hydrochloride; vitamin B12 such as cyanocobalamin, hydroxocobalamin, and deoxyadenosylcobalamin; folic acids such as folic acid and pteroylglutamic acid; nicotinic acids such as nicotinic acid and nicotinamide; pantothenic acids such as pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-panthesine, D-pantethine, coenzyme A, and pantothenyl ethyl ether; biotins such as biotin and bioticin; and vitamin-like factors such as carnitine, ferulic acid, α-lipoic acid, pyrroloquinoline quinone, and orotic acid.

Examples of amino acids or derivatives thereof include betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine, leucine, isoleucine, valine, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, and creatine.

Examples of cell activation components include amino acids such as γ-aminobutyric acid and ε-aminopropionic acid; vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids; α-hydroxy acids such as glycolic acid and lactic acid; tannins; flavonoids; saponin; allantoin; and photosensitizer No. 301.
Examples of anti-aging ingredients include hydrolyzed soy protein, retinoids (retinol and its derivatives, retinoic acid, retinal, etc.), pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, and mevalonolactone.

Examples of blood circulation-promoting ingredients include ingredients derived from plants (e.g., ginseng, angelica, arnica, ginkgo, fennel, emmeisou, Dutch oak, chamomile, Roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake mushroom, European hawthorn, European juniper, cnidium rhizome, swertia britannica, thyme, clove, tangerine peel, angelica tree, peach kernel, spruce, carrot, garlic, butcher's broom, grape, peony, horse chestnut, melissa, yuzu, coix seed, rosemary, rose hip, tangerine peel, angelica tree, spruce, peach, apricot, walnut, and corn); and glucosyl hesperidin.

Examples of keratin softening ingredients include lanolin, urea, alpha hydroxy acids (phytic acid, lactic acid, lactate salts, glycolic acid, salicylic acid, malic acid, gluconic acid, etc.), and sulfur.
Examples of whitening ingredients include ascorbic acid and its derivatives, arbutin, tocopherol, tranexamic acid, hydroquinone, kojic acid, salicylic acid derivatives, placenta extract, linoleic acid, nicotinamide, and plant ingredients having whitening properties (e.g., extracts of saxifrage, aloe, etc.).
Examples of astringent ingredients include zinc paraphenolsulfonate, zinc oxide, menthol, and ethanol.

Other active ingredients can be used alone or in combination of two or more.

[Formulation]
The topical composition of the present invention can be mixed with a base or carrier commonly used in pharmaceuticals, quasi-drugs, or cosmetics, and, if necessary, additives, to form a topical composition for pharmaceuticals, quasi-drugs, or cosmetics.

The form of the pharmaceutical composition for external use is not particularly limited, and examples include liquids, suspensions, emulsions, creams, ointments, gels, liniments, lotions, patches, and aerosols. These preparations can be manufactured according to the methods described in the General Provisions for Preparations of the Japanese Pharmacopoeia, 15th Edition. Among these, liquids, suspensions, emulsions, creams, ointments, gels, lotions, and patches are preferred, and creams, emulsions, ointments, lotions, and gels are more preferred.

When the composition is made into a topical composition for quasi-drugs or cosmetics, it can be in the same form as the above-mentioned pharmaceuticals. Other examples include sticks and sheets in which nonwoven fabric is impregnated with a drug solution. Among these, liquids, suspensions, emulsions, creams, ointments, gels, lotions, sticks, and sheets are preferred, with creams, emulsions, ointments, lotions, sticks, and gels being more preferred.

In the case of creams and emulsions that contain an oily base and an aqueous base, they may be either W/O type (water-in-oil type) or O/W type (oil-in-water type), but from the viewpoint of usability, the O/W type is preferred. In the case of a base that contains water, the amount of water varies depending on the form of the cosmetic product and is not particularly limited. In some cases, the amount of water is preferably 5 to 99%, more preferably 8 to 95%, and even more preferably 10 to 90%. In the case of a base that does not contain water, an ointment containing the above-described lower alcohol and/or the above-described polyhydric alcohol as a base can be used.

Specific examples of applications of the composition for external use as a quasi-drug or cosmetic include basic cosmetics such as lotion, milky lotion, gel, cream, beauty essence, sunscreen cosmetics, packs, masks, hand cream, body lotion, and body cream; cleansing cosmetics such as face wash, hand soap, makeup remover, body shampoo, shampoo, rinse, and treatment; face makeup cosmetics such as foundation and makeup base; lip cosmetics such as lipstick, lip cream, lip gloss, and lip liner; hair cosmetics such as hair rinse, hair treatment, hair conditioner, hair gel, hair mousse, hair mist, hair lotion, and styling agent. Among these, a composition for external use for skin is particularly preferred. That is, the composition for external use of the present invention can be a composition for external use for skin for pharmaceuticals, quasi-drugs, or cosmetics. The formulation form of the composition for external use for skin is the same as that of the composition for external use of the present invention. Additionally, the bases or carriers, additives, and active ingredients that can be used, as well as the preferred ones thereof, are the same as those in the topical composition of the present invention.

[container]
The topical composition of the present invention can be stored and used in a container of a shape and material appropriately selected according to the purpose and application. Specific examples of the container include spray type, bottle type, tube type, jar type, dropper type, dispenser type, stick type, pouch bag, and cheer pack. Normally, due to its characteristics, the higher the concentration of cholesterol or phytosterol, the higher the viscosity or hardness of the formulation increases, and it has been extremely difficult to make a topical composition that can be stored in an extrusion or discharge type container such as a spray, bottle, tube, or dispenser. However, the topical composition of the present invention can be used in a preferred state from the viewpoint of ease of discharging from the container, so that the freedom of designing a formulation containing high concentrations of cholesterol or phytosterol can be increased. That is, even if the formulation contains high concentrations of cholesterol or phytosterol, it can be easily used in a wide variety of containers such as jars and sticks, as well as sprays, bottles, tubes, and dispensers, ensuring the freedom of product design, and is particularly useful for tube, dispenser, and bottle type containers.

Examples of container materials include polyethylene terephthalate, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ABS resin, ethylene vinyl alcohol resin, polystyrene, glass, and metal (aluminum, etc.). Taking into consideration strength, flexibility, weather resistance, and component stability, these materials can be used as container materials by performing various coating processes, combining these materials by mixing, for example, or laminating them. Among these, it is preferable to use polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ethylene vinyl alcohol resin, and metal (aluminum, etc.).

[How to use]
The topical composition of the present invention can be suitably used to treat various skin diseases and skin troubles, taking advantage of the physiological activity of cholesterol and/or phytosterol. In particular, it can be suitably used to prevent, treat, or improve skin troubles such as atopic dermatitis, and rough skin and rough hands caused by aging or dryness. For example, application to the skin can improve the barrier function and improve the skin condition by increasing the moisture retention, and can be expected to have the effect of improving and preventing the above-mentioned symptoms, and may also have the effect of suppressing itching associated with the above-mentioned symptoms. Furthermore, it can be particularly effective in the harsh hand skin environment of northern countries.

The container for storing the composition and the method for using the composition are the same as those for the topical composition of the present invention.

[How to improve usability]
The present invention also includes a method for improving the feel of a topical composition containing (A) cholesterol and/or phytosterol. According to the present invention, the feel of a topical composition can be improved by preparing a topical composition containing (A) 3% by mass or more of cholesterol and/or phytosterol; (B) a higher alcohol having 12 to 22 carbon atoms and/or a higher fatty acid having 12 to 22 carbon atoms; and (C) 20% by mass or less of silicone oil. Here, the improvement of the feel of a topical composition means, for example, in the case of a cream, that the composition spreads well and blends well when applied to the skin, that the composition is not sticky and moisturizes well, that the composition maintains a suitable softness even in a low-temperature environment, or that the composition has excellent spreadability. In some cases, the composition can be a formulation that does not freeze even at low temperatures, for example, at about −20° C.

[others]
The topical composition of the present invention also has excellent stability. Here, excellent stability means, but is not limited to, that the stability is guaranteed even at high or low temperatures. Specifically, it means that the precipitation of cholesterol and/or phytosterol or a salt thereof is suppressed even when the topical composition is stored at a low temperature, for example, at 4°C for one week, or that changes in appearance such as separation, precipitation, and coloration are suppressed even after storage at 50°C or 40°C for a certain period of time.

In the method of the present invention, the conditions of the topical composition containing (A) 3% by mass or more of cholesterol and/or phytosterol; (B) higher alcohol having 12 to 22 carbon atoms and/or higher fatty acid having 12 to 22 carbon atoms; and (C) 20% by mass or less of silicone oil are the same as those used in the topical composition described above. Furthermore, the product obtained by this method can be used in a known or commonly used dosage and administration manner, from once to several times a day, depending on the purpose, etc.

Next, the present invention will be specifically explained using examples, but the present invention is not limited to the following examples.

[Cholesterol and/or Phytosterol Compatibility Confirmation Test]
In preparing the topical composition of the embodiment, the combination of the (A) component, the (B) component, and the (C) component used in the embodiment was used to carry out compatibility test.On the other hand, the comparative preparation example of the combination of the components different from the embodiment was also prepared, and the difference in compatibility was confirmed.In detail, when the components shown in Table 1 and Table 2 were mixed and stirred under the heating condition of 80°C, the dissolution state of the components was examined, and evaluated according to the following criteria.
If the mixture dissolved within 20 minutes: 4
If the mixture is still slightly dissolved after 20 minutes: 3
If the mixture is still partially dissolved after 20 minutes: 2
If the mixture is almost undissolved after 20 minutes:

This confirmation test revealed that the compatibility of the combination of components (A), (B) and (C) corresponding to the topical composition of the example was particularly excellent compared to the comparative preparation example.

[Moisture occlusion test]
Compositions having the formulations shown in Table 3 below were prepared, and their moisture-retaining properties were evaluated by the following method.

(Moisture occlusion)
A designated amount of water was poured into a glass bottle, and the bottle was covered with a cellulose filter (Visking tube) coated with a designated amount of the preparation. The bottle was left to stand at 30°C and 65RH for 24 hours, and the amount of water evaporation was measured using a balance (sartorius CPA3245). (N=3 each) The values of the amount of water evaporation of Comparative Example 1-2 and Example 1-1 when the amount of water evaporation of Comparative Example 1-1, in which the amount of cholesterol is 0%, was taken as 100% are shown in Table 3 and Figure 1. Comparative Example 1-2 had a lower amount of water evaporation than Comparative Example 1-1, and Example 1-1 had a significantly lower amount of water evaporation than Comparative Example 1-1 and Comparative Example 1-2. From these results, it was found that by increasing the concentration of cholesterol, the water evaporation suppression effect was increased and the water occlusion effect was enhanced.

[Viscosity evaluation]
Compositions were prepared according to the formulations shown in Table 4 below, and the viscosities of the samples that were incubated at 25° C. for 2 hours after preparation were measured (measured using a VISCOMETER TV-10 under the conditions of an M4 rotor at 1.5 rpm for 60 seconds).

[Usability evaluation]
The topical compositions of the Examples and Comparative Examples shown in Table 5 were prepared according to a conventional method. They were then subjected to evaluation of the sensation of use. The sensation of use (skin compatibility upon application, stickiness after application) was evaluated by the following method.
Six panelists applied an appropriate amount (approximately 20 mg) of each test formulation to an area of 2 cm x 2 cm on the inside of their forearms and were asked to rate the sensation of use on a 5-point scale. The 5-point scale scores were based on the following criteria:
Blends well with the skin when applied. 5 points: Blends well with the skin. 4 points: Blends well with the skin to some extent. 3 points: Can't say either way. 2 points: Doesn't blend well with the skin at all. 1 point: Doesn't blend well with the skin at all.

Stickiness after application: 5 points: not sticky 4 points: not very sticky 3 points: neither sticky nor sticky 2 points: slightly sticky 1 point: sticky

The average scores of the six people and the results of evaluation based on the average scores and the following criteria are shown in Table 5.
◎ 4 points or more 〇 3.5 points or more but less than 4 points △ 3 points or more but less than 3.5 points × Less than 3 points

The results of the evaluation of the usability of the compositions of the examples and comparative examples, as well as the results of the cholesterol and/or phytosterol precipitation inhibition confirmation test, are shown in the table below.

[Usability evaluation]
<Easy to dispense from the tube>
Compositions were prepared according to the formulations shown in Table 6 below, and the resulting compositions were filled into tube containers with a discharge diameter of 5 mm. A panel of six people evaluated the ease of dispensing from the tube according to the following criteria.
3 points: Easy to remove from the tube 2 points: Slightly easy to remove from the tube 1 point: Difficult to remove from the tube

The average scores and the results of evaluation based on the average scores according to the following criteria are shown in Table 8.
◎2.5 points or more 〇2 points or more but less than 2.5 points × Less than 2 points

The results of the usability evaluation of the compositions of the examples and comparative examples, as well as the results of the cholesterol and/or phytosterol precipitation inhibition confirmation test, are shown in Table 6.

[Stability test]
Compositions for external use having the compositions shown in Tables 4 to 9 were prepared according to conventional methods. These compositions for external use were then filled into transparent screw-top glass bottles and stored at 25° C., 4° C., or 40° C. for 2 weeks. Each test preparation was evaluated based on the solubility of component A) during production, the state of the preparation immediately after production (precipitation), and the stability over time (precipitation/separation).

(Solubility of the oil phase during manufacture)
The solubility of the oil phase of the test sample during production was visually observed and evaluated according to the following criteria.
〇No abnormalities △Slight residue is visible ×Remnants are visible

(Formulation immediately after manufacture)
Immediately after the preparation of the test sample, the condition of the preparation was observed visually and under a microscope (Keyence VH-Z500R) at a magnification of 500 times, and evaluated according to the following criteria.
〇No abnormalities △Slight precipitation observed ×Precipitation observed

(Stability over time)
The test samples were left at 4° C. or 25° C. for 2 weeks and then returned to room temperature. The state of the preparation was observed visually and under a microscope (Keyence VH-Z500R) at 500x magnification and evaluated according to the following criteria.
〇No abnormalities △Slight separation or precipitation observed ×Separation or precipitation observed

Comparative Examples 2-4 and 2-5 exceeded the viscosity measurement condition of 400 Pa·s, and could not be measured using the above viscometer. It is generally known that formulations with high viscosity, for example when the container is a tube or bottle, tend to be poor in terms of ejection from the container and usability. However, in the examples in which higher alcohol was blended as (B), when the cholesterol concentration was 3% by mass or more, it was found that the increase in viscosity was suppressed more than in formulations that did not blend higher alcohol as component (B). This tendency is shown diagrammatically in Figure 2.

The effect of the present invention that the composition of the present invention can provide a composition with excellent usability even when it contains high concentration of cholesterol is particularly remarkable when the concentration of cholesterol is 3% by mass or more.That is, the topical composition of the embodiment contains high cholesterol of 3% by mass, 5% by mass, 8% by mass, and 10% by mass, but the viscosity increase is significantly suppressed, and it is within the range that can be measured by a simple viscometer.It can be said that the topical composition of the embodiment contains high concentration of cholesterol of 10% by mass, but can be designed to be stable and has a viscosity within the range that can be measured by a viscometer with an upper limit of 400 Pa·s, which is a surprising and extremely remarkable effect.

Comparing the compositions of Examples 3-1 to 3-2, which contain 3% by mass of cholesterol, with the compositions of Comparative Examples 3-1 to 3-3, the compositions of Comparative Examples 3-1 to 3-3, which do not contain higher alcohol as component (B) and use a large amount of solvent to dissolve cholesterol, did not provide a satisfactory feel when used. Also, the composition of Comparative Example 3-2, which contains 30% methylpolysiloxane, did not provide a satisfactory feel when used. This shows that there is an appropriate range for the amount of component C. Comparing the compositions of Examples 3-3 to 3-4 and Comparative Examples 3-4 to 3-5, which contain 5% by mass of cholesterol, shows that the compositions of Comparative Examples, which require a large amount of solvent to dissolve cholesterol, provide a poor feel when used, as with the case of 3% by mass. Also, even when the amount of cholesterol is increased to 8% by mass or 10% by mass, the compositions of Examples containing higher alcohol as component (B) can be used to prepare formulations with a good feel when used.

Comparing the compositions of Example 4-3 and Comparative Example 4-2, which contain 10% cholesterol by mass, the results showed that the composition of the Example, which contains a higher alcohol to reduce the amount of solvent, was easier to come out of the tube than the composition of the Comparative Example, which contains a large amount of solvent to dissolve cholesterol. Even under the condition of a cholesterol concentration of 8% by mass, the composition of Example 4-2, which contains a higher alcohol, was easier to come out of the tube than Comparative Example 4-1. Since the higher the cholesterol concentration, the more difficult it is to come out of the tube, the results showed that even in Example 4-1, which has a concentration of 5% by mass, it was naturally easier to come out of the tube. As a result, by combining cholesterol with higher alcohols and higher fatty acids, it became possible to easily incorporate high concentrations of cholesterol, which is effective as an anti-inflammatory ingredient, and the formulation also had excellent usability and could be flexibly adapted to various usage sensations.

[Hardness evaluation]
(Hardness test)
Using an Anton Paar MCR102, the storage modulus and loss modulus (Pa) were measured when the strain (%) was changed after incubation at a specific temperature (4°C or 25°C) for 1 minute. The measurement was performed at 17 points using a PP25 rotor. The results of the strain, storage modulus, and loss modulus (Pa) are shown in Figure 3.

When the strain is increased, fluidity is generated in the formulation at the point where the storage modulus and loss modulus intersect. Therefore, it can be said that the smaller the strain value (γ) at the intersection point of the storage modulus and loss modulus, the better the dischargeability from the tube and the elongation of the formulation.
When comparing the composition of Example 3-6 containing 10 mass % cholesterol with the composition of Comparative Example 4-2, the composition of the Example has a smaller strain value (γ) at the intersection of the storage modulus and the loss modulus. From this point of view, it can be said that the composition of the Example is superior in usability, and it is clear that the effects of the invention are realized.

The compositions shown in the examples achieved inhibition of cholesterol and/or phytosterol precipitation. In the compositions of Comparative Examples 5-1 to 5-3 produced using cetyl phosphate, when squalane and hydrogenated soybean phospholipid or polar oil (white beeswax, tri-2-ethylhexyl glyceryl) were used as a solvent and stabilizer without using component (B), the oil phase was insufficiently dissolved and precipitation was observed immediately after production. In Comparative Example 5-4, a large amount of sorbitan stearate was added to dissolve cholesterol, and although there was no precipitation during or immediately after production, the composition lacked stability over time. When the compositions of Comparative Examples 6-1 to 6-4 produced using a nonionic surfactant were similarly examined without using component (B), the oil phase was insufficiently dissolved and precipitation was observed immediately after production when only squalane, polyoxyethylene hydrogenated castor oil 60, and sorbitan stearate in Comparative Example 6-1 were used. Next, in Comparative Example 6-2, a large amount of sorbitan stearate was blended, and although there was no precipitation during or immediately after production, the result was lack of stability over time. Furthermore, when the (A) component was 8% by mass or 10% by mass, precipitation was observed during and immediately after production, even when a large amount of sorbitan stearate was blended. In the composition of Comparative Example 5-2, which was formulated by dissolving cholesterol using polar oil as a solvent, and the composition of Comparative Example 6-4, which was formulated with 10% by mass of cholesterol by containing a large amount of surfactant and liquid oil, separation was observed at 25°C for 2 weeks. In all Comparative Examples other than Comparative Example 5-4, precipitation was observed at 4°C for 2 weeks, and in most of the Comparative Examples, precipitation was observed even at 25°C for 2 weeks. In the compositions of the Examples, no stability problems were observed, and it was confirmed that high concentrations of cholesterol could be stably dissolved with a smaller amount of solvent by using the (B) component. In addition, the comparative compositions, which had relatively few problems in terms of stability at 25°C, had problems with stickiness, poor compatibility with the skin, and usability, as shown in Tables 5 and 6. Furthermore, in the case of Comparative Examples 5-1 to 5-3, which did not dissolve during production and precipitated immediately afterwards, the precipitation made the feel of use completely unacceptable, and it was considered important to stabilize and dissolve cholesterol as in the examples.

Figure 4 shows a microscope image of the composition of the example immediately after production. Furthermore, Figure 5 shows a microscope image of the composition of the comparative example immediately after production. Figures 6 and 7 show microscope images of the composition of the comparative example in which precipitation was observed due to stability over time. The precipitation site is indicated with a →. Furthermore, Figure 6 is a microscope image of the composition of the comparative example after storage at 4°C for 2 weeks, and Figure 7 is a microscope image of the composition of the comparative example after storage at 25°C for 2 weeks. It was clearly confirmed that in the composition of the comparative example, precipitation was observed that was clearly distinguishable not only by visual inspection but also under a microscope.

The results of the stability tests shown in Tables 4 to 9 and Figures 4 to 7 show that the topical compositions of the Examples are stable and do not precipitate over a wide range of temperatures, from as low as 4°C to 25°C and 40°C. These results show that the topical compositions of the Examples can maintain good usability even when stored in containers with small outlets, such as tubes and dispensers.

[Banishing Evaluation]
An appropriate amount (about 20 mg) of each test preparation was applied to an area of 2 cm x 2 cm of artificial leather, and the state of white residue when the preparation was spread with a finger was observed and evaluated according to the following criteria.
〇No white residue△Some white residue×White residue

Figure 9 shows photographs of the evaluation results of the compositions of the examples and comparative examples that were subjected to the vanishing test. It was found that Example 7-1 did not leave a white residue compared to Comparative Example 7-1. Since leaving a white residue generally leads to poor compatibility, it was found that it is desirable to incorporate dimethicone as component C when creating a sample with a good feel.

The compositions shown in the following formulation examples are prepared. All values are in mass %.
(Formulation example)

Claims (6)

(A) cholesterol and/or phytosterol: 3% by mass or more and 15% by mass or less;
(B) a higher alcohol having 12 to 22 carbon atoms and/or a higher fatty acid having 12 to 22 carbon atoms;
A composition for external use comprising: (C) 0.5% by mass or more and 20% by mass or less of a silicone oil; and (D) 5% by mass or more and 30% by mass or less of a polyhydric alcohol,
Here, the ratio of the content of the (B) component to the content of the (A) component is 1 to 6 parts by mass,
(B) component contains at least cetanol or stearyl alcohol;
Composition for external use. The topical composition according to claim 1, wherein the polyhydric alcohol (D) is at least one selected from the group consisting of diethylene glycol, polyethylene glycol (PEG), propylene glycol (PG), butylene glycol (BG), dipropylene glycol (DPG), glycerin, diglycerin, isoprene glycol, diethylene glycol, ethoxydiglycol, polypropylene glycol, polyglycerin, pentanediol, octanediol, and hexanediol. The composition for external use according to claim 1 or 2, wherein the total content of surfactants is 15% by mass or less. The composition for external use according to any one of claims 1 to 3, wherein the total content of oily components is 40.1% by mass or less. The composition for external use according to any one of claims 1 to 4, which is an oil-in-water (O/W) type cream contained in a tube type, jar type, pouch bag, or cheer pack container. (A) cholesterol and/or phytosterol: 3% by mass or more and 15% by mass or less;
(B) a higher alcohol having 12 to 22 carbon atoms and/or a higher fatty acid having 12 to 22 carbon atoms;
(C) 0.5% by mass or more and 20% by mass or less of a silicone oil; and (D) 5% by mass or more and 30% by mass or less of a polyhydric alcohol are used in combination,
Here, the ratio of the content of the (B) component to the content of the (A) component is 1 to 6 parts by mass,
A method for improving the spreadability of a topical composition by including at least cetanol or stearyl alcohol as a component (B).

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