Cosmetic

Abstract

To provide a cosmetic exhibiting superior affinity with the skin during application.SOLUTION: A cosmetic in one aspect according to the present invention includes (a) a pyrimidinylpyrazole compound or a pharmacologically acceptable salt thereof, (b) at least one hydrophilic surfactant selected from the group consisting of polyoxyethylene hydrogenated castor oil and polyoxyethylene phytosterol, (c) at least one lipophilic surfactant selected from the group consisting of polyglyceryl diisostearate, sorbitan sesquiisostearate, and sorbitan sesquioleate, and (d) an oil component.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to cosmetics.

Background Art

[0002] In recent years, cosmetics formulated with micronized oil have the advantage of providing a skin-friendly feel and excellent smoothness during application, and thus can widely achieve a use feel according to personal preference and a skin-improving effect.

[0003] For example, a transparent to translucent liquid cosmetic containing an oil, a hydrophilic surfactant selected from polyoxyethylene hydrogenated castor oil and polyoxyethylene phytosterol, and a lipophilic surfactant selected from polyglyceryl diisostearate, sorbitan sesquiisostearate, and sorbitan sesquioleate, and having an L value of 60 or more, wherein isostearyl alcohol accounts for 60% by mass or more of the oil, is known to have a non-greasy and soft use feel (see Patent Document 1).

[0004] However, the cosmetic described in Patent Document 1 has a problem that the quick adaptability during application is not sufficiently satisfactory.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] In view of the above, an object of an embodiment of the present invention is to provide a cosmetic excellent in quick adaptability during application.

Means for Solving the Problems

[0007] In order to solve the above problems, one embodiment of the cosmetic according to the present invention comprises: (a) a pyrimidylpyrazole compound represented by the following general formula (1) or a pharmacologically acceptable salt thereof,

[0008]

Chem.

Advantages of the Invention

[0009] According to one embodiment of the present invention, a cosmetic excellent in the quick adaptability during application can be provided.

Mode for Carrying Out the Invention

[0010] Hereinafter, embodiments of the present invention will be described in detail. Note that the embodiments are not limited by the following description and can be appropriately changed without departing from the gist of the present invention. In addition, in this specification, "~" indicating a numerical range means including the numerical values described before and after it as the lower limit value and the upper limit value, unless otherwise specified.

[0011] (Cosmetic) The cosmetic according to one embodiment contains (a) a pyrimidylpyrazole compound represented by the following general formula (1) or a pharmacologically acceptable salt thereof, (b) at least one hydrophilic surfactant selected from the group consisting of polyoxyethylene hydrogenated castor oil and polyoxyethylene phytosterol, (c) at least one lipophilic surfactant selected from the group consisting of polyglyceryl diisostearate, sorbitan sesquiisostearate, and sorbitan sesquioleate, and (d) an oil component, and further contains other components as necessary.

[0012]

Chem.

[0013] <(a) Pyrimidylpyrazole compound represented by general formula (1) or a pharmacologically acceptable salt thereof> The pyrimidylpyrazole compound represented by general formula (1) or a pharmacologically acceptable salt thereof (hereinafter sometimes referred to as “component (a)”) has very low cytotoxicity.

[0014] In general formula (1), R 1 , R 3 , R 4 , and R 6 each independently represent an alkyl group having 1 to 3 carbon atoms. In one embodiment, the “alkyl group having 1 to 3 carbon atoms” represented by R 1 , R 3 , R 4 , and R 6 is a linear, branched, or cyclic saturated hydrocarbon group having 1 to 3 carbon atoms. Also, in one embodiment, “each independently” means that R 1 , R 3, R 4 , and R 6 may each be a different alkyl group having 1 to 3 carbon atoms or the same alkyl group having 1 to 3 carbon atoms.

[0015] R 1 , R 3 , R 4 , and R 6 Examples of the alkyl group having 1 to 3 carbon atoms represented by R 1 , R 3 , R 4 , and R 6 include, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropyl group, etc. Among these, as the alkyl group having 1 to 3 carbon atoms represented by R

[0016] In the general formula (1), R 2 and R 5 each independently represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. In one embodiment, the "alkyl group having 1 to 3 carbon atoms" represented by R 2 and R 5 is a linear, branched, or cyclic saturated hydrocarbon group having 1 to 3 carbon atoms. Also, in one embodiment, "each independently" means that R 2 and R 5 may each be a different hydrogen atom or alkyl group having 1 to 3 carbon atoms or the same hydrogen atom or alkyl group having 1 to 3 carbon atoms.

[0017] R 2 and R 5 Examples of the alkyl group having 1 to 3 carbon atoms represented by R 2 and R 5 include, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropyl group, etc. As R

[0018] Examples of pharmacologically acceptable salts of the pyrimidylpyrazole compound represented by the general formula (1) include inorganic acid salts such as hydrochloride, hydrobromide, sulfate, and phosphate; and organic acid salts such as acetate, propionate, citrate, lactate, oxalate, maleate, fumarate, succinate, tartrate, and methanesulfonate.

[0019] The pyrimidylpyrazole compound represented by the general formula (1) may be synthesized appropriately by a known method or a commercially available product may be used.

[0020] Typical synthesis examples of the pyrimidylpyrazole compound represented by the general formula (1) will be described below, but are not limited thereto. Examples of the method for synthesizing the pyrimidylpyrazole compound represented by the general formula (1) include a method of synthesizing by the reaction shown in the following Scheme 1. The reaction shown in the following Scheme 1 can be carried out, for example, according to the methods described in JP-A-62-000404, Dharmpal S Dodd et al., Tetrahedron Letters, Volume 45, Issue 22, 2004, p.4265-4267, Gazzetta Chemica Italiana, Vol. 93, Parte I, 1963, p. 100, etc.

[0021]

Chemical formula

[0022] In Scheme 1, the reaction between the hydrazine compound represented by the general formula (2) and the 1,3-dicarbonyl compound represented by the general formula (3a) or the 1-sulfonyl-3-carbonyl compound represented by the general formula (3b) can be carried out, for example, in a suitable solvent such as methanol, under an acid catalyst such as hydrochloric acid or acetic acid, with heating if necessary.

[0023] For the pharmacologically acceptable salts of the pyrimidylpyrazole compound represented by the general formula (1), those appropriately synthesized by known methods may be used, or commercially available products may be used. As a synthesis example of the pharmacologically acceptable salt of the pyrimidylpyrazole compound represented by the general formula (1), there is a method of converting it to an acid addition salt appropriately selected from known methods for the pyrimidylpyrazole compound represented by the general formula (1). Examples of the acid used in the method of converting to an acid addition salt include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid; and organic acids such as acetic acid, propionic acid, citric acid, lactic acid, oxalic acid, maleic acid, fumaric acid, succinic acid, tartaric acid, and methanesulfonic acid.

[0024] The hydrazine compound represented by the general formula (2) used as the starting material in Scheme 1 may be appropriately synthesized by known methods or commercially available products may be used. As a synthesis example of the hydrazine compound represented by the general formula (2), there is a method of synthesizing it by the reaction shown in Scheme 2 below. The reaction shown in Scheme 2 below can be carried out, for example, according to the method described in JP-A-8-208620.

[0025]

Chemical formula

[0026] In addition, the hydrazine compound represented by the general formula (2) used as the starting material in Scheme 1 can also be synthesized from the pyrimidine compound represented by the general formula (5) having a leaving group Z by the reaction shown in the following Scheme 3. Examples of the leaving group Z in the pyrimidine compound represented by the general formula (5) include halogen. The reaction shown in the following Scheme 3 can be carried out, for example, according to the methods described in Takeo Naito et al., Chemical and Pharmaceutical Bulletin, 1969, Vol. 17, No. 7, p. 1467-1478, Kaname Takagi et al., Chemical and Pharmaceutical Bulletin, 1963, Vol. 11, No. 11, p. 1382-1388, Kenzo Shirakawa, Yakugaku Zasshi, 1953, Vol. 73, No. 6, p. 635-639, etc.

[0027]

Chemical formula

[0028] Regarding other compounds used in the reactions of Schemes 1 to 3, those appropriately synthesized by known methods may be used, or commercially available products may be used.

[0029] In the reactions of Schemes 1 to 3, when a functional group is present in the molecule and this functional group may interfere with the reaction or there is a risk of such interference, it is preferable to use an appropriate protecting group to efficiently proceed the reaction. The use of the protecting group can be carried out, for example, according to the methods described in Theodora W. Greene, Peter G. M. Wuts, GREENE'S PROTECTIVE GROUPS IN ORGANIC SYNTHESIS, etc.

[0030] In the reactions of Schemes 1 to 3, when isomers such as conformational isomers, geometric isomers, and optical isomers exist, pure isomers or geometric isomers can be obtained by appropriately selecting the raw materials and reaction conditions and performing separation operations. The pyrimidylpyrazole compound represented by the general formula (1) or a pharmacologically acceptable salt thereof includes pure isomers or mixtures thereof.

[0031] Examples of the pyrimidylpyrazole compound represented by the general formula (1) or a pharmacologically acceptable salt thereof include R 1 , R 3 , R 4 , and R 6 being methyl groups, and R 2 and R 5 being hydrogen atoms, and 2-(3,5-dimethylpyrazol-1-yl)-4,6-dimethylpyrimidine hydrochloride (also referred to as "dimethylpyrazolyl dimethylpyrimidine hydrochloride") is particularly preferred.

[0032] In the cosmetic according to one embodiment, the content of the component (a) is not particularly limited and can be appropriately selected according to the purpose. However, based on the total mass of the cosmetic, 0.01% by mass to 5% by mass is preferred, 0.1% by mass to 3% by mass is more preferred, and 0.5% by mass to 2% by mass is even more preferred. When the content of the component (a) is 0.1% by mass or more, the familiarity speed can be suitably improved. Also, if the content of the component (a) is excessively blended, a remarkable effect commensurate with the increase in amount may not be obtained, and it may affect formulation design and usability, etc. Therefore, it is preferably 5% by mass or less.

[0033] <At least one hydrophilic surfactant selected from the group consisting of polyoxyethylene hydrogenated castor oil and polyoxyethylene phytosterol> The hydrophilic surfactant contained in the cosmetic according to one embodiment is at least one hydrophilic surfactant selected from the group consisting of polyoxyethylene (hereinafter sometimes abbreviated as "POE") hydrogenated castor oil and polyoxyethylene phytosterol (hereinafter sometimes referred to as "component (b)").

[0034] <<Polyoxyethylene hydrogenated castor oil>> The average number of moles of ethylene oxide added to polyoxyethylene hydrogenated castor oil is not particularly limited and can be appropriately selected according to the purpose. However, 20 to 100 moles are preferred, and 60 to 100 moles are more preferred.

[0035] Specific examples of polyoxyethylene hydrogenated castor oil include POE(40) hydrogenated castor oil, POE(60) hydrogenated castor oil, POE(100) hydrogenated castor oil, etc. The numerical values in parentheses indicate the average number of moles of ethylene oxide added.

[0036] As the polyoxyethylene hydrogenated castor oil, those appropriately synthesized by known methods may be used, or commercially available products may be used. Examples of commercially available polyoxyethylene hydrogenated castor oil include NIKKOL HCO-40 (POE(40) hydrogenated castor oil), NIKKOL HCO-60 (POE(60) hydrogenated castor oil), NIKKOL HCO-100 (POE(100) hydrogenated castor oil) (manufactured by Nikko Chemicals Co., Ltd.), EMALEX HC-40 (POE(40) hydrogenated castor oil), EMALEX HC-60 (POE(60) hydrogenated castor oil), EMALEX HC-100 (POE(100) hydrogenated castor oil) (manufactured by Nippon Emulsion Co., Ltd.), UNIOX HC-40 (POE(40) hydrogenated castor oil), UNIOX HC-60 (POE(60) hydrogenated castor oil), UNIOX HC-100 (POE(100) hydrogenated castor oil) (manufactured by NOF Corporation), etc.

[0037] <<Polyoxyethylene phytosterol>> The average number of moles of ethylene oxide added to polyoxyethylene phytosterol is not particularly limited and can be appropriately selected according to the purpose. However, 10 to 50 moles are preferred, and 10 to 30 moles are more preferred.

[0038] Specific examples of polyoxyethylene phytosterol include POE(10) phytosterol, POE(20) phytosterol, POE(30) phytosterol, etc. The numerical value in parentheses indicates the average number of moles of ethylene oxide added.

[0039] For polyoxyethylene phytosterol, those synthesized appropriately by known methods may be used, or commercially available products may be used. Examples of commercially available polyoxyethylene phytosterol include, for example, NIKKOL BPS-10 (POE(10) phytosterol), NIKKOL BPS-20 (POE(20) phytosterol), NIKKOL BPS-30 (POE(30) phytosterol) (all of the above are manufactured by Nikko Chemicals Co., Ltd.), etc.

[0040] In the cosmetic according to one embodiment, the content of component (b) is not particularly limited and can be appropriately selected according to the purpose. However, with respect to the total mass of the cosmetic, 0.01% by mass to 3% by mass is preferable, 0.05% by mass to 1% by mass is more preferable, and 0.1% by mass to 0.2% by mass is even more preferable. When the content of component (b) is 0.01% by mass or more, the cosmetic can be stably emulsified. Also, when the content of component (b) is 3% by mass or less, stickiness is less likely to occur.

[0041] <At least one lipophilic surfactant selected from the group consisting of polyglyceryl diisostearate, sorbitan sesquiisostearate, and sorbitan sesquioleate> The lipophilic surfactant contained in the cosmetic according to one embodiment is at least one lipophilic surfactant selected from the group consisting of polyglyceryl diisostearate, sorbitan sesquiisostearate, and sorbitan sesquioleate (hereinafter, may be referred to as "component (c)").

[0042] <<Polyglyceryl diisostearate>> The polyglyceryl diisostearate is not particularly limited as long as it can act as a lipophilic surfactant, and it can be appropriately selected according to the purpose. For example, diglyceryl diisostearate, triglyceryl diisostearate, etc. can be mentioned. These may be used alone or in combination of two or more.

[0043] As the polyglyceryl diisostearate, those appropriately synthesized by known methods may be used, or commercially available products may be used. Examples of commercially available products of polyglyceryl diisostearate include, for example, WOGEL-18DV (diglyceryl diisostearate, manufactured by Matsumoto Fine Chemical Co., Ltd.), Cosmol 42V (diglyceryl diisostearate, manufactured by Nisshin Oillio Group, Ltd.), EMALEX DISG-2 (diglyceryl diisostearate), EMALEX DISG-3 (triglyceryl diisostearate) (above, manufactured by Nippon Emulsion Co., Ltd.), Lysolrex PGIS22 (diglyceryl diisostearate), Lysolrex PGIS32 (triglyceryl diisostearate) (above, manufactured by Kao Alcohol Industries Co., Ltd.), etc.

[0044] <<Sorbitan sesquiisostearate>> As the sorbitan sesquiisostearate, those appropriately synthesized by known methods may be used, or commercially available products may be used. Examples of commercially available products of sorbitan sesquiisostearate include, for example, Cosmol 182V (manufactured by Nisshin Oillio Group, Ltd.), EMALEX SPIS-150 (manufactured by Nippon Emulsion Co., Ltd.), NIKKOL SI-15RV (manufactured by Nikko Chemicals Co., Ltd.), etc.

[0045] <<Sorbitan sesquioleate>> Sorbitan sesquioleate may be synthesized appropriately by a known method or a commercially available product may be used. Examples of commercially available products of sorbitan sesquioleate include, for example, EMALEX SPO-150 (manufactured by Nippon Emulsion Co., Ltd.), NIKKOL SO-15V (manufactured by Nikko Chemicals Co., Ltd.), NOFABLE® SO-852S (manufactured by NOF Corporation), Cosmoll 82 (manufactured by Nisshin Oillio Group, Ltd.), and the like.

[0046] In the cosmetic according to one embodiment, the content of component (c) is not particularly limited and can be appropriately selected according to the purpose. However, it is preferably 0.01% by mass to 2% by mass, more preferably 0.01% by mass to 1.5% by mass, and still more preferably 0.05% by mass to 1% by mass based on the total mass of the cosmetic. When the content of component (c) is 0.01% by mass or more, the cosmetic can be stably emulsified. Further, when the content of component (c) is 2% by mass or less, stickiness is less likely to occur.

[0047] <(d) Oil component> The oil component (hereinafter sometimes referred to as "component (d)") is not particularly limited and can be appropriately selected from known oil components used in cosmetics. For example, fats and oils, waxes, hydrocarbon oils, higher fatty acids, higher alcohols, ester oils, silicone oils, oil-soluble drugs, and the like can be mentioned. These may be used alone or in combination of two or more.

[0048] Examples of fats and oils include vegetable fats and oils such as avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, sesame oil, persic oil, wheat germ oil, sasanqua oil, castor oil, linseed oil, safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, sinagiri oil, Japanese cedar oil, jojoba oil, germ oil, cocoa butter, coconut oil, hydrogenated coconut oil, palm oil, palm kernel oil, mokuro kernel oil; and animal fats and oils such as egg yolk oil, horse fat, beef tallow, mutton fat, hydrogenated beef tallow, lard, beef bone fat, beef foot fat, and the like.

[0049] Examples of waxes include beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, spermaceti wax, whale wax, montan wax, rice bran wax, lanolin, kapok wax, lanolin acetate, liquid lanolin, sugarcane wax, isopropyl lanolin fatty acid, hexyl laurate, reduced lanolin, jojoba wax, hard lanolin, shellac wax, and the like.

[0050] Examples of hydrocarbon oils include linear, branched, or volatile hydrocarbon oils. Specific examples of hydrocarbon oils include liquid paraffin, squalane, isoparaffin, α-olefin oligomer, polybutene, microcrystalline wax, hydrogenated polydecene, hydrogenated castor oil, and the like.

[0051] Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, 12-hydroxystearic acid, undecylenic acid, lanolin fatty acid, isostearic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, and the like.

[0052] Examples of higher alcohols include alcohols having 6 or more carbon atoms. Specific examples of higher alcohols include lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, cetostearyl alcohol, monostearyl glycerin ether (batyl alcohol), 2-decyltetradecyl alcohol, 2-octyldodecanol, lanolin alcohol, cholesterol, phytosterol, hexyl dodecanol, isostearyl alcohol, octyldodecanol, and other linear or branched higher alcohols.

[0053] Examples of ester oils include glycerin triisooctanoate, glycerin triisopalmitate, octyl isopalmitate, isopropyl isostearate, isostearyl isostearate, isocetyl isostearate, hexyl isostearate, myristyl isostearate, isocetyl octanoate, cetyl isooctanoate, isostearyl octanoate, isodecyl isononanoate, octyldodecyl dimethyloctanoate, oleyl myristate, isostearyl erucate, isocetyl stearate, octyl stearate, isostearyl palmitate, isocetyl palmitate, octyl palmitate, isostearyl myristate, isocetyl myristate, octyldodecyl myristate, decyl myristate, isopropyl palmitate, isopropyl myristate, trimethylolpropane triisostearate, neopentyl glycol dicaprate, dioctyl sebacate, octyldodecyl 12-stearoyloxystearate, dioctyldodecyl stearoylglutamate, dioctyl adipate, diisostearyl malate, octyl methoxycinnamate, octyldodecyl lactate, isostearyl lactate, octyl dimethylaminobenzoate, and the like.

[0054] Examples of silicone oils include volatile cyclic silicones, volatile dimethylpolysiloxanes, methylphenylsilicones, and the like.

[0055] Examples of oil-soluble drugs include fat-soluble vitamins such as vitamin A, retinol, retinol palmitate, benzyl nicotinate, dl-α-tocopherol nicotinate, vitamin D2, and tocopherol.

[0056] The component (d) may be used alone or in combination of two or more. Among these, a liquid oil component that is liquid at 25°C is preferable, and it is more preferable to contain at least one selected from the group consisting of isostearic acid, hydrogenated polydecene, tocopherol, and isostearyl alcohol because it is less likely to cause stickiness and can provide oxidation stability, an emollient effect, a refreshing feeling, and the like.

[0057] In the cosmetic according to one embodiment, the content of the component (d) is not particularly limited and can be appropriately selected according to the purpose. However, with respect to the total mass of the cosmetic, 0.01% by mass to 3% by mass is preferable, 0.1% by mass to 1% by mass is more preferable, and 0.2% by mass to 0.8% by mass is even more preferable. When the content of the component (d) is 0.01% by mass or more, the cosmetic can be stably emulsified. Further, when the content of the component (d) is 3% by mass or less, stickiness is less likely to occur.

[0058] <Other components> The cosmetic according to one embodiment may contain other components other than the component (a), the component (b), the component (c), and the component (d). The other components are not particularly limited and can be appropriately selected from known components used in cosmetics. For example, glycols, glycerins, sugar alcohols, saccharides, powders, pigments, dyes, polymers, solvents, pH adjusters, surfactants other than the component (b) and the component (c), fragrances, drugs other than the component (a), and the like can be mentioned. These may be used alone or in combination of two or more.

[0059] The content of the other components in the cosmetic according to one embodiment is not particularly limited as long as the effects of the cosmetic according to one embodiment are not impaired, and can be appropriately selected according to the purpose.

[0060] <<Glycols>> Examples of glycols include propylene glycol, dipropylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, and the like.

[0061] <<Glycerins>> Examples of glycerins include glycerin, diglycerin, polyglycerin, and the like.

[0062] <<Sugar alcohols>> Examples of sugar alcohols include sorbitol, mannitol, maltitol, xylitol, and erythritol.

[0063] <<Sugars>> Examples of sugars include fructose, glucose, galactose, maltose, lactose, and trehalose.

[0064] <<Powder>> The powder may be an inorganic powder or an organic powder.

[0065] Examples of inorganic powders include mica, talc, kaolin, sericite (sericite), muscovite, phlogopite, synthetic mica, red mica, biotite, lithia mica, synthetic mica, anhydrous silicic acid (silica), aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, aluminum oxide, barium sulfate, zeolite, titanium oxide, zinc oxide, and boron nitride.

[0066] Examples of organic powders include polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene powder, calcium carbonate powder, magnesium carbonate powder, styrene-acrylic acid copolymer resin powder, and cellulose powder.

[0067] <<Pigments>> Examples of pigments include inorganic pigments, organic pigments, pearl pigments, and metal powder pigments.

[0068] Examples of inorganic pigments include inorganic white pigments such as titanium dioxide and zinc oxide; inorganic red pigments such as iron oxide (red iron oxide); inorganic yellow pigments such as yellow iron oxide and yellow ocher; black pigments such as black iron oxide and carbon black; inorganic green pigments such as chromium oxide, chromium hydroxide, and cobalt titanate; and inorganic blue pigments such as ultramarine and Prussian blue.

[0069] Examples of organic pigments include Pigment Red 3, Pigment Red 104, Pigment Red 106, Pigment Red 201, Pigment Red 202, Pigment Red 204, Pigment Red 205, Pigment Red 220, Pigment Red 226, Pigment Red 227, Pigment Red 228, Pigment Red 230, Pigment Red 401, Pigment Red 405, Pigment Red 505, Pigment Orange 203, Pigment Orange 204, Pigment Orange 205, Pigment Yellow 4, Pigment Yellow 5, Pigment Yellow 202, Pigment Yellow 203, Pigment Yellow 205, Pigment Yellow 401, Pigment Blue 1, Pigment Blue 404, Pigment Green 3, and their zirconium lakes, barium lakes, or aluminum lakes, etc.

[0070] Examples of pearl pigments include titanium oxide-coated mica, colored titanium oxide-coated mica, bismuth oxychloride, fish scale foil, etc.

[0071] Examples of metal powder pigments include aluminum powder, copper powder, etc.

[0072] <<Dye>> Examples of dyes include natural dyes such as chlorophyll, β-carotene, etc.

[0073] <<Polymers>> Examples of polymers include plant-based polymers, animal-based polymers, microbial-based polymers, starch-based polymers, cellulose-based polymers, alginic acid-based polymers, vinyl-based polymers, acrylic-based polymers, inorganic water-soluble polymers, etc. These polymers may act as thickeners.

[0074] Examples of plant-based polymers include gum arabic, tragacanth gum, galactan, guar gum, carob gum, karaya gum, gellan gum, carrageenan, pectin, agar, etc.

[0075] Examples of animal-based polymers include collagen, casein, albumin, gelatin, etc.

[0076] Examples of microbial-based polymers include xanthan gum, dextran, succinoglucan, pullulan, etc.

[0077] Examples of starch-based polymers include vegetable starches such as corn, wheat, potato, and rice starch; carboxymethyl starch; methyl hydroxypropyl starch, and the like.

[0078] Examples of cellulose-based polymers include methyl cellulose, nitrocellulose, ethyl cellulose, methyl hydroxypropyl cellulose, hydroxyethyl cellulose, sodium cellulose sulfate, hydroxypropyl cellulose, sodium carboxymethyl cellulose, crystalline cellulose, and the like.

[0079] Examples of alginic acid-based polymers include sodium alginate, propylene glycol alginate ester, and the like.

[0080] Examples of vinyl-based polymers include polyvinyl alcohol, polyvinyl acetate, polyvinyl methyl ether, polyvinyl pyrrolidone, copolymers of vinyl pyrrolidone and vinyl acetate, carboxyvinyl polymer, and the like.

[0081] Examples of acrylic polymers include sodium polyacrylate, polyethyl acrylate, alkanolamine polyacrylate, copolymers of alkyl methacrylate and dimethylaminoethyl methacrylate, poly(2-acrylamido-2-methylpropane sulfonic acid), polymethacryloyloxy trimethyl ammonium, and the like.

[0082] Examples of inorganic water-soluble polymers include polyethyleneimine, cationic polymers, bentonite, magnesium aluminum silicate, laponite, hectorite, silicic anhydride, and the like.

[0083] <<Solvent>> Examples of the solvent include water, lower alcohols, etc. Examples of the lower alcohol include alcohols having 5 or less carbon atoms. Specific examples of the lower alcohol include methanol, ethanol, propyl alcohol, isopropyl alcohol, 2-amino-2-methyl-1-propanol, 2-amino-2-methyl-1,3-propanediol, etc.

[0084] <<pH adjuster>> Examples of the pH adjuster include potassium hydroxide, sodium hydroxide, triethanolamine, sodium carbonate, lactic acid, citric acid, sodium citrate, glycolic acid, succinic acid, tartaric acid, malic acid, sodium hydrogen carbonate, ammonium hydrogen carbonate, etc.

[0085] <<Surfactant>> Examples of the surfactant include anionic surfactants, cationic surfactants, nonionic surfactants, amphoteric surfactants, etc.

[0086] Examples of anionic surfactants include, for example, fatty acid soaps such as soap bases, sodium laurate, and sodium palmitate; higher alkyl sulfate ester salts such as sodium lauryl sulfate and potassium lauryl sulfate; alkyl ether sulfate ester salts such as triethanolamine POE lauryl sulfate and sodium POE lauryl sulfate; N-acyl sarcosinic acids such as sodium lauroyl sarcosinate; higher fatty acid amide sulfonic acids such as sodium N-myristoyl-N-methyl taurate and sodium coconut fatty acid methyl tauride; phosphate ester salts such as POE stearyl ether phosphate; sulfosuccinates such as sodium monolauroyl monoethanolamide POE sulfosuccinate and sodium lauryl polypropylene glycol sulfosuccinate; alkylbenzene sulfonate salts such as sodium linear dodecylbenzene sulfonate and triethanolamine linear dodecylbenzene sulfonate; N-acyl glutamate salts such as disodium N-stearoyl glutamate and monosodium N-stearoyl glutamate; higher fatty acid ester sulfate ester salts such as sodium hardened coconut oil fatty acid glycerol sulfate; sulfated oils such as rape oil; POE alkyl ether carboxylic acids; POE alkyl allyl ether carboxylate salts; higher fatty acid ester sulfonate salts; secondary alcohol sulfate ester salts; higher fatty acid alkanolamide sulfate ester salts; sodium lauroyl monoethanolamide succinate; sodium caseinate, and the like.

[0087] Examples of cationic surfactants include, for example, alkyltrimethylammonium salts such as stearyltrimethylammonium chloride and lauryltrimethylammonium chloride; dialkyldimethylammonium salts such as distearyldimethylammonium chloride; alkylpyridinium salts such as cetylpyridinium chloride; alkyl quaternary ammonium salts; alkyl dimethylbenzylammonium salts; alkylisoquinolinium salts; dialkylmorphonium salts; POE alkylamines; alkylamine salts; polyamine fatty acid derivatives; amyl alcohol fatty acid derivatives; benzalkonium chloride, and the like.

[0088] Examples of nonionic surfactants include lipophilic nonionic surfactants other than component (c), hydrophilic nonionic surfactants other than component (b), and the like. Examples of lipophilic nonionic surfactants other than component (c) include sorbitan fatty acid esters such as sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, and sorbitan trioleate; glycerin polyglycerin fatty acids such as monoricinoleic acid glycerin, glycerin monostearate, sesquioleic acid glycerin, and glycerin monostearate malate; propylene glycol fatty acid esters such as propylene glycol monostearate; glycerin alkyl ethers; POE-methylpolysiloxane copolymers, and the like. Examples of hydrophilic nonionic surfactants other than component (b) include POE sorbitan fatty acid esters such as POE sorbitan monooleate and POE sorbitan monostearate; POE sorbit fatty acid esters such as POE sorbit monolaurate, POE sorbit monooleate, and POE sorbit monostearate; POE glycerin fatty acid esters such as POE glycerin monooleate and POE glycerin distearate; POE fatty acid esters such as POE monooleate, POE distearate, and POE monodioleate; POE alkyl ethers such as POE lauryl ether, POE oleyl ether, and POE cholestanol ester; POE alkylphenyl ethers such as POE octylphenyl ether and POE nonylphenyl ether; POE-POP alkyl ethers such as POE-POP monobutyl ether, POE-POP cetyl ether, and POE-POP glycerin ether; POE beeswax-lanolin derivatives such as POE sorbit beeswax; alkanolamides such as coconut fatty acid diethanolamide and fatty acid isopropanolamide; POE propylene glycol fatty acid ester; POE fatty acid amide, POE alkylamine; sucrose fatty acid ester, alkyl ethoxydimethylamine oxide, and the like.

[0089] Examples of the amphoteric surfactant include imidazoline-based amphoteric surfactants such as 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt; betaine-based surfactants such as amide betaine and sulfobetaine.

[0090] <<Drug>> Examples of the drug include salt-type drugs, vitamins, ultraviolet absorbers, chelating agents, preservatives, plant extracts, humectants, anti-inflammatory agents, whitening agents, cooling agents, amino acids, antioxidants, bactericides, etc.

[0091] - Salt-type drug - The salt-type drug means a water-soluble drug capable of forming a salt. The salt-type drug is not particularly limited as long as it is a water-soluble drug that can be usually formulated in cosmetics, and can be appropriately selected according to the purpose. For example, salts of L-ascorbic acid or its derivatives, salts of tranexamic acid or its derivatives, salts of alkoxysalicylic acid or its derivatives, salts of glutathione or its derivatives, etc. can be mentioned.

[0092] L-ascorbic acid is generally called vitamin C, has cell respiration, enzyme activation, and collagen formation effects due to its strong reducing action, and has a melanin reduction effect. Examples of L-ascorbic acid derivatives include L-ascorbic acid monoesters such as L-ascorbic acid monophosphate ester and L-ascorbic acid-2-sulfate ester; L-ascorbic acid triesters such as L-ascorbic acid triphosphate ester; L-ascorbic acid glucosides such as L-ascorbic acid-2-glucoside.

[0093] Examples of tranexamic acid derivatives include dimers of tranexamic acid such as trans-4-(trans-aminomethylcyclohexanecarbonyl)aminomethylcyclohexanecarboxylic acid hydrochloride; ester compounds of tranexamic acid and hydroquinone such as 4'-hydroxyphenyl ester of trans-aminomethylcyclohexanecarboxylic acid; ester compounds of tranexamic acid and gentisic acid such as 2-(trans-4-aminomethylcyclohexylcarbonyloxy)-5-hydroxybenzoic acid; amide compounds of tranexamic acid such as trans-4-aminomethylcyclohexanecarboxylic acid methylamide, trans-4-(p-methoxybenzoyl)aminomethylcyclohexanecarboxylic acid, trans-4-guanidinomethylcyclohexanecarboxylic acid, and the like.

[0094] Examples of alkoxysalicylic acids include those in which the hydrogen atom at the 3-position, 4-position, or 5-position of salicylic acid is substituted with an alkoxy group. The alkoxy group as the substituent is preferably any one of a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, and an isobutoxy group, and more preferably a methoxy group or an ethoxy group. Specific examples of alkoxysalicylic acids include 3-methoxysalicylic acid, 3-ethoxysalicylic acid, 4-methoxysalicylic acid, 4-ethoxysalicylic acid, 4-propoxysalicylic acid, 4-isopropoxysalicylic acid, 4-butoxysalicylic acid, 5-methoxysalicylic acid, 5-ethoxysalicylic acid, 5-propoxysalicylic acid, and the like.

[0095] The salts of the drug are not particularly limited, and examples include alkali metal salts or alkaline earth metal salts such as sodium salt, potassium salt, and calcium salt; ammonium salts; amino acid salts, and the like.

[0096] - Vitamins - Examples of vitamins include water-soluble vitamins such as vitamin B6 hydrochloride, pantothenyl ethyl ether, pyridoxine hydrochloride, nicotinamide, pantothenic acid, and biotin.

[0097] - UV Absorbents - Examples of ultraviolet absorbers include benzoic acid-based ultraviolet absorbers such as para-aminobenzoic acid; anthranilic acid-based ultraviolet absorbers such as methyl anthranilate; salicylic acid-based ultraviolet absorbers such as octyl salicylate; cinnamic acid-based ultraviolet absorbers such as isopropyl paramethoxycinnamate and octyl paramethoxycinnamate; ultraviolet absorbers such as urocanic acid and ethyl urocanate; benzophenone-based ultraviolet absorbers such as 2-hydroxy-4-methoxybenzophenone and dihydroxybenzophenone; benzotriazole-based ultraviolet absorbers; 2-phenylbenzimidazole-5-sulfonic acid, and the like.

[0098] -Chelating agent- Examples of chelating agents include citramalic acid, agaric acid, glyceric acid, shikimic acid, hinokitiol, gallic acid, tannic acid, caffeic acid, trisodium ethylenediamine-N,N,N',N'-tetraacetate trihydrate (EDTA-3Na), ethylenediamine diacetic acid, diethylenetriamine pentaacetic acid, phytic acid, polyphosphoric acid, metaphosphoric acid, their analogs, their alkali metal salts, their carboxylic acid esters, and the like.

[0099] -Preservative- Examples of preservatives include benzoic acid, salicylic acid, paraoxybenzoic acid esters (such as methyl paraben, ethyl paraben, butyl paraben, etc.), sorbic acid, parachlorometacresol, hexachlorophene, benzalkonium chloride, chlorhexidine chloride, trichlorocarbanilide, photosensitizer, phenoxyethanol, and the like.

[0100] -Plant extract- Examples of plant extracts include Houttuynia cordata extract, Paeonia lactiflora extract, Glycyrrhiza glabra extract, Paeonia suffruticosa extract, Calendula officinalis extract, Luffa cylindrica extract, Saxifraga stolonifera extract, Eucalyptus globulus extract, Cinnamomum camphora extract, Malus sieversii extract, Youngia japonica extract, seaweed extract, Thymus vulgaris extract, and the like.

[0101] -Humectant- Examples of the humectant include polyethylene glycol (hereinafter referred to as PEG), sodium chondroitin sulfate, sodium hyaluronate, sodium lactate, glucosamine, cyclodextrin, PEG / polypropylene glycol (PPG)-17 / 4 dimethyl ether, and the like. Further, the glycols, the glycerols, the sugar alcohols, and the saccharides can also be used as the humectant.

[0102] - Anti-inflammatory agent - Examples of the anti-inflammatory agent include azulene, glycyrrhizin, lysozyme chloride, pyridoxine hydrochloride, sulfur, and the like.

[0103] - Whitening agent - Examples of the whitening agent include arbutin, 4-methoxysalicylic acid, tranexamic acid, ethyl vitamin C, magnesium ascorbyl phosphate, and the like. Further, the salt-type drugs can also be used as the whitening agent.

[0104] - Cooling agent - Examples of the cooling agent include L-menthol, camphor, and the like.

[0105] - Antioxidant - Examples of the antioxidant include ascorbic acid, α-tocopherol, carotenoid, and the like.

[0106] <Dosage form> The dosage form of the cosmetic according to one embodiment is not particularly limited and can be appropriately selected according to the purpose. However, a liquid cosmetic is preferred, a liquid emulsified cosmetic is more preferred, and an oil-in-water emulsion is even more preferred.

[0107] The product form of the cosmetic according to one embodiment is not particularly limited and can be appropriately selected according to the purpose. For example, facial or body skin care such as lotion, emulsion, essence, cream, etc., or cosmetics for hair care; sunscreen cosmetics; self-tanning cosmetics; skin cleansing cosmetics such as makeup remover; ointments, etc. can be mentioned. Further, the product form of the cosmetic according to one embodiment may be a form impregnated in a base material such as a pack. Among these, as the product form of the cosmetic according to one embodiment, since it is excellent in the ease of adaptation during application, skin care cosmetics are preferred, and lotion is more preferred.

[0108] <Manufacturing method> The manufacturing method of the cosmetic according to one embodiment is not particularly limited, and it can be manufactured according to the method usually used for cosmetics, preferably liquid cosmetics. As a specific example of the manufacturing method of the cosmetic according to one embodiment, first, a water phase is prepared by dissolving the (a) component and the (b) component, and further, if necessary, a water-soluble component appropriately selected from other components in water. Next, the (c) component and the (d) component, and further, if necessary, a water-insoluble component appropriately selected from other components are mixed to prepare an oil phase. When preparing the oil phase, it is preferable to further add an amphiphilic component. Examples of the amphiphilic component include the above-mentioned amphoteric surfactant. Finally, a method of manufacturing the cosmetic according to one embodiment by adding the oil phase to the water phase and stirring can be mentioned.

Examples

[0109] Examples and comparative examples are given below to more specifically explain the embodiment, but the embodiment is not limited by these synthesis examples, examples, and comparative examples. In the examples and comparative examples, the content of each component shown in Tables 1 and 2 below indicates "mass%" based on the total mass of the cosmetic, unless otherwise specified, and all values are in terms of pure components.

[0110] (Examples 1 to 5) Each component was mixed with the composition and content (mass %) shown in Table 1 and Table 2 below, and the lotions of Examples 1 to 5 were respectively prepared. Specifically, first, the water-soluble components among the component (a), the component (b), and other components were dissolved in water to prepare an aqueous phase. Next, the water-insoluble components among the component (c), the component (d), and other components were mixed to prepare an oil phase. Finally, the oil phase was added to the aqueous phase and stirred to obtain the oil-in-water type lotions of Examples 1 to 5.

[0111] Immediately after preparing the lotions of Examples 1 to 5, the pH of each lotion was measured with a pH meter (HORIBA LAQUA pH METER F-71, manufactured by Horiba, Ltd.). The evaluation results are shown in Table 1 and Table 2 below.

[0112] (Comparative Example 1) In the preparation of the lotions of Examples 1 to 5, except that the component (a) was not added as shown in the composition and content (mass %) shown in Table 1 below, the lotion of Comparative Example 1 was obtained in the same manner as in Examples 1 to 5. Also, the pH was measured in the same manner as in Examples 1 to 5.

[0113] (Comparative Example 2) In the preparation of the lotions of Examples 1 to 5, except that the component (a) was not added and ascorbic acid-2-glucoside, a salt-type drug, was added as a comparative component of the component (a) as shown in the composition and content (mass %) shown in Table 2 below, the lotion of Comparative Example 2 was obtained in the same manner as in Examples 1 to 5. Also, the pH was measured in the same manner as in Examples 1 to 5.

[0114] <Evaluation of ease of skin adaptation> The ease of skin adaptation of each lotion of Examples 1 to 5 and Comparative Example 2 was evaluated by the following method. Ten professional evaluators confirmed the ease of skin adaptation when applying each lotion of Examples 1 to 5 and Comparative Examples 1 and 2 to the skin, and using the lotion of Comparative Example 1 as a control, evaluated based on the following evaluation criteria. The evaluation results are shown in Table 1 and Table 2 below. In this evaluation, there was no response indicating that the skin adaptation was worse (slower) compared to the control. [Evaluation criteria for ease of skin adaptation] A: Seven or more out of ten respondents answered that they got used to it faster compared to the control. B: Three or more and six or less out of ten respondents answered that they got used to it faster compared to the control. C: Two or less out of ten respondents answered that they got used to it faster compared to the control.

[0115]

Table 1

[0116]

Table 2

[0117] Note that 2-(3,5-dimethylpyrazol-1-yl)-4,6-dimethylpyrimidine hydrochloride (dimethylpyrazolyl dimethylpyrimidine hydrochloride) used in the examples is a compound represented by the following structural formula (1) and was produced by the method described in Patent No. 4586108.

[0118]

Chemical formula

[0119] Examples of the aspects of the present invention include, for example, the following. <1> (a) A pyrimidylpyrazole compound represented by the following general formula (1) or a pharmacologically acceptable salt thereof, and

[0120]

Chemical formula

[0121] As described above, the present invention has been described based on specific embodiments and examples. However, these embodiments and examples are merely presented as examples, and the present invention is not limited by the above embodiments and examples. The above embodiments can be implemented in various other forms, and various combinations, omissions, replacements, additions, changes, etc. can be made without departing from the gist of the invention. These embodiments and their modifications are included in the scope and gist of the invention, and are included in the invention described in the claims and its equivalent scope.

Claims

1. (a)A pyrimidylpyrazole compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof, 【Chemical 1】 (In the general formula (1), R １ , R ３ , R ４ , and R ６ each independently represent an alkyl group having 1 to 3 carbon atoms, and R ２ and R ５ each independently represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms.) (b)At least one hydrophilic surfactant selected from the group consisting of polyoxyethylene hydrogenated castor oil and polyoxyethylene phytosterol, (c)At least one lipophilic surfactant selected from the group consisting of polyglyceryl diisostearate, sorbitan sesquiisostearate, and sorbitan sesquioleate, (d)An oil component, A cosmetic characterized by containing these.

2. The cosmetic according to Claim 1, which is an oil-in-water emulsion.

3. R in the above-mentioned (a) pyrimidylpyrazole compound represented by the general formula (1) or a pharmacologically acceptable salt thereof ２ and R ５ are hydrogen atoms, and the cosmetic according to claim 1.

4. R in the above-mentioned (a) pyrimidylpyrazole compound represented by the general formula (1) or a pharmacologically acceptable salt thereof １ , R ３ , R ４ , and R ６ is a methyl group, The cosmetic according to claim 1 or 2.

5. The cosmetic according to Claim 1, wherein the content of the pyrimidylpyrazole compound represented by the general formula (1) or a pharmaceutically acceptable salt thereof in (a) is 0.1% by mass to 5% by mass.

6. The cosmetic according to Claim 1, wherein the content of the hydrophilic surfactant in (b) is 0.01% by mass to 3% by mass.

7. The cosmetic according to Claim 1, wherein the content of the lipophilic surfactant in (c) is 0.01% by mass to 2% by mass.

8. The cosmetic according to Claim 1, wherein the content of the oil component in (d) is 0.01% by mass to 3% by mass.

9. The cosmetic according to Claim 1, wherein the oil component in (d) is at least one selected from the group consisting of isostearic acid, hydrogenated polydecene, tocopherol, and isostearyl alcohol.

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