Oil-in-water type topical skin preparation

Abstract

To provide an oil-in-water topical skin preparation that stably contains ibuprofen piconol.SOLUTION: An oil-in-water topical skin preparation contains (A) ibuprofen piconol and (B) an antioxidant.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an oil-in-water type topical skin preparation containing ibuprofen picolol.

Background Art

[0002] Ibuprofen picolol (IPPN) is a drug whose efficacy for acne vulgaris was first recognized as a topical non-steroidal agent. In addition to its anti-inflammatory and analgesic effects, it also has an inhibitory effect on lipase and the lipase activity of bacteria themselves. Therefore, topical preparations containing ibuprofen picolol have excellent effects on acne. On the other hand, there is a problem that the content decreases over time. In response to this problem, a pharmaceutical composition containing 0.7 to 1.5% by mass of isopropylmethylphenol, which is used as a substance having antibacterial action, in the composition has been proposed. However, isopropylmethylphenol is a component that is hardly soluble in water, and a composition containing 0.7% by mass or more in the composition may precipitate over time, and a solution alternative to isopropylmethylphenol has been demanded.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] The present invention has been made in view of the above circumstances, and an object thereof is to provide an oil-in-water type topical skin preparation in which ibuprofen picolol is stably formulated.

Means for Solving the Problems

[0005] As a result of intensive studies to achieve the above object, the present inventors have found that the above problems can be solved by combining (A) ibuprofen piconol and (B) an antioxidant, and have thus completed the present invention.

[0006] Accordingly, the present invention provides the following oil-in-water type topical skin preparation. 1. An oil-in-water type topical skin preparation containing (A) ibuprofen piconol and (B) an antioxidant. 2. The topical skin preparation according to 1, wherein the component (B) is at least one selected from ascorbic acid and its salts, sulfurous acid and its salts, thiosulfuric acid and its salts, and glycine and its salts. 3. The topical skin preparation according to 1 or 2, wherein the content of the component (B) is 0.01% by mass or more in the topical skin preparation. 4. The topical skin preparation according to any one of 1 to 3, having a pH of 4 to 9. 5. The topical skin preparation according to any one of 1 to 4, wherein the mass ratio in the topical skin preparation represented by (B) / (A) is 0.002 to 0.5.

Effects of the Invention

[0007] According to the present invention, it is possible to provide an oil-in-water type topical skin preparation in which ibuprofen piconol is stably formulated.

Modes for Carrying Out the Invention

[0008] Hereinafter, the present invention will be described in detail. [Component (A)] The component (A) of the present invention is ibuprofen piconol, and any one can be used as long as it is used in ordinary pharmaceuticals. For example, those listed in the Japanese Pharmacopoeia pharmaceutical standards can be used. Among them, ibuprofen piconol conforming to the Japanese Pharmacopoeia pharmaceutical standards is preferable.

[0009] The content of component (A) is 1% by mass or more in the oil-in-water type topical skin preparation (hereinafter may be simply abbreviated as topical skin preparation), so that the anti-inflammatory effect can be easily obtained, the formation of acne caused by acne bacteria can be suppressed, the inflammation (red pimples) can be alleviated, and the therapeutic effect on eruptions and pimples can be improved. On the other hand, by setting it to 5% by mass or less, the ease of spreading on the skin becomes good, the stability of component (A) is improved, and the side effects caused by component (A) are less likely to occur. The content of component (A) is particularly preferably 3% by mass in the topical skin preparation.

[0010] [Component (B)] Component (B) of the present invention is an antioxidant and can be used alone or in combination of two or more. Component (A) is stabilized by the antioxidant which is component (B). Although this mechanism is not clear, it is considered that the antioxidant which is component (B) undergoes hydrolysis prior to component (A), thereby suppressing the hydrolysis of component (A) and improving the stability. Examples of the antioxidant include ascorbic acid, pyrosulfurous acid, sulfurous acid, sodium bisulfite, glycine, hydroquinone, cysteine and salts thereof. Among them, one or more selected from ascorbic acid and its salts, sulfurous acid and its salts, and glycine and its salts are preferable. In particular, the combined use of ascorbic acid and its salts and sulfurous acid and its salts is preferable because the stability of component (A) is high and the coloring of the topical skin preparation during storage is suppressed.

[0011] Ascorbic acid or its salts can be those commercially available as components of external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics, and can be used alone or in combination of two or more. These are usually in the L-form, with ascorbic acid being preferred, and ascorbate salts may also be used. Examples of ascorbate salts include salts with organic bases (such as salts with tertiary amines like trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, pyridine salt, etc., basic ammonium salts like arginine salt, etc.), salts with inorganic bases (such as alkali metal salts like sodium salt, potassium salt, alkaline earth metal salts like calcium salt, magnesium salt, ammonium salt, aluminum salt, etc.). Among them, sodium salt and potassium salt are preferred. Specifically, sodium ascorbate, potassium ascorbate, sodium ascorbic acid-2-sulfate, etc. can be mentioned, and from the viewpoint of significantly achieving the effects of the present invention, ascorbic acid can be preferably used. As ascorbic acid or its salts, for example, L(+)-ascorbic acid (vitamin C) (manufactured by Fujifilm Wako Pure Chemical Corporation, Fuso Chemical Industry Co., Ltd., Kyowa Pharmaceutical Chemical Co., Ltd., Iwaki Pharmaceutical Co., Ltd., etc.) can be used.

[0012] Examples of sulfurous acid or its salts, and thiosulfuric acid or its salts include pyrosulfurous acid, sulfurous acid, hydrogen sulfite, thiosulfuric acid, and their salts, etc., and they can be used alone or in combination of two or more. Among them, from the viewpoint of significantly achieving the effects of the present invention, sodium salt or potassium salt is preferred, and sodium pyrosulfite, potassium pyrosulfite, sodium sulfite, potassium sulfite, dried sodium sulfite (anhydrous sodium sulfite), sodium hydrogen sulfite, potassium hydrogen sulfite, sodium thiosulfate, potassium thiosulfate are preferred, sodium pyrosulfite, sodium sulfite, sodium hydrogen sulfite, sodium thiosulfate are more preferred, and sodium pyrosulfite, sodium sulfite, sodium hydrogen sulfite are even more preferred. As sulfurous acid or its pharmaceutically acceptable salts, sodium pyrosulfite (manufactured by Fujifilm Wako Pure Chemical Corporation) etc. can be used.

[0013] As glycine or its salt, for example, it can be used in the form of hydrochloride, hydrobromide, sulfate, acetate, etc., and can be used alone or in combination of two or more. From the viewpoint of significantly exhibiting the effects of the present invention, glycine can be preferably used. As glycine or its salt, glycine (FUJIFILM Wako Pure Chemical Corporation) can be used.

[0014] The content of component (B) is not particularly limited as long as the effects of the present invention are achieved, and it can be appropriately selected and used in consideration of the feeling of use on the skin and the effects. From the viewpoint of the stability of component (A), 0.01% by mass or more in the external preparation for skin is preferable, and from the viewpoints of preventing discoloration and suppressing odor of the external preparation for skin, 0.5% by mass or less is preferable. Among them, 0.05 to 0.3% by mass in the external preparation for skin is more preferable.

[0015] The mass ratio in the external preparation for skin represented by (B) / (A) is preferably 0.002 to 0.5, and more preferably 0.01 to 0.3. By setting the mass ratio to 0.002 or more, the stability of component (A) becomes better, and by setting it to 0.5 or less, the degree of discoloration of the external preparation for skin can be suppressed.

[0016] [Optional components] In the external preparation for skin of the present invention, in addition to the above components, various optional components that can be formulated in the external preparation for skin, for example, physiologically active components other than component (A), surfactants, pH adjusters, bases, thickeners, chelating agents, preservatives, coloring agents, fragrances, etc., can be appropriately formulated alone or in combination of two or more. Among them, it is preferable to formulate a surfactant and a thickener.

[0017] (A) As physiologically active ingredients other than the component, there may be mentioned vitamin A and its pharmaceutically acceptable derivatives, quaternary ammonium salt type bactericides, allantoin and its pharmaceutically acceptable derivatives, glycyrrhetinic acid and its pharmaceutically acceptable salts, glycyrrhizic acid and its pharmaceutically acceptable salts, salicylic acid and its pharmaceutically acceptable derivatives, azulene and its pharmaceutically acceptable derivatives, zinc oxide, tocopherol acetate, tocopherol nicotinate, tocopherol succinate, tocopherol linolenate, aminocaproic acid, hydrocortisone, prednisolone and their pharmaceutically acceptable derivatives, sodium chondroitin sulfate, heparin-like substances, hyaluronic acid and its pharmaceutically acceptable salts, bufexamac, chlorpheniramine, lidocaine, l-menthol, panthenol, urea, plant extracts (for example, comfrey, cinnamon, peony, button mushroom, ginseng, peony root), etc. Here, the "pharmaceutically acceptable derivative" means an ester, ether, alkylated product, glycoside, etc. of the described compound.

[0018] Examples of vitamin A and its pharmaceutically acceptable derivatives include vitamin A fatty acid esters, and for example, retinol acetate, retinol palmitate, retinol propionate, etc. can be exemplified. In particular, the combined use of retinol palmitate is suitable from the viewpoint of promoting skin metabolism and suppressing acne pustules. As vitamin A and its pharmaceutically acceptable derivatives, retinol palmitate [1.74 million IU / g], DSM Nutritional Products Japan Co., Ltd., etc. can be used. By containing vitamin A and its pharmaceutically acceptable derivatives, without disturbing or enhancing the pharmacological action of the (A) component, it becomes a highly useful topical skin preparation for acne vulgaris because it has an anti-inflammatory effect and promotes turnover to replace hyperkeratosis in the infundibulum of the hair follicle to a normal state. The content of vitamin A and its pharmaceutically acceptable derivatives in the topical skin preparation is preferably 0.1 to 0.6% by mass. By setting it above the lower limit, a highly useful topical skin preparation as described above can be obtained, and by setting it below the upper limit, a bactericidal effect can be easily obtained.

[0019] As the quaternary ammonium salt type bactericide, known ones can be used, and they can be used alone or in combination of two or more. Examples of the component (B) include benzethonium chloride, cetylpyridinium chloride, benzalkonium chloride, etc. Among them, benzethonium chloride, which has a high inhibitory effect on the abnormal growth and sterilization of Propionibacterium acnes, a lipophilic and facultative anaerobic bacillus that normally resides on the skin, and on the abnormal growth and sterilization of the epidermal resident bacteria involved in the exacerbation of skin symptoms, is preferred. Examples of the bactericide for acne medications include ethanol and isopropylmethylphenol, and they may be used in combination with the quaternary ammonium salt type bactericide. The quaternary ammonium salt type bactericide is preferably 0.01 to 0.5% by mass in the skin external preparation. By setting it above the lower limit, the bactericidal action against acne bacteria can be easily obtained, and by setting it below the upper limit, the irritation to the skin and mucous membranes can be suppressed.

[0020] Examples of the surfactant include sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexanoate, and diglycerol sorbitan tetra-2-ethylhexanoate; propylene glycol fatty acid esters such as propylene glycol monostearate; polyoxyethylene hydrogenated castor oil derivatives such as polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), and polyoxyethylene hydrogenated castor oil 80; polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), and polyoxyethylene (20) sorbitan isostearate; polyoxyethylene glyceryl monococoate; glycerin alkyl ether; alkyl glucoside; polyoxyalkylene alkyl ethers such as polyoxyethylene cetyl ether; amines such as stearylamine and oleylamine; silicone surfactants such as polyoxyethylene-methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone. Among these, from the viewpoint of the stability of component (A), polyoxyethylene sorbitan fatty acid ester and polyoxyethylene hydrogenated castor oil are preferred, and polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), and polyoxyethylene hydrogenated castor oil 60 (HCO-60) are more preferred. From the viewpoint of the stability of vitamin A in component (A), the surfactant is preferably 0.1 to 5% by mass, more preferably 0.5 to 2% by mass in the external preparation for skin.

[0021] Examples of the acid for the pH adjuster include inorganic acids such as acetic acid, hydrochloric acid, phosphoric acid, and boric acid, organic acids such as lactic acid, tartaric acid, and citric acid. Examples of the alkali agent include sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate, alkylamide, monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, tromethamine, and other various amines. Examples of the organic salts include phosphates such as potassium hydrogen phosphate and sodium hydrogen phosphate, sodium citrate, sodium lactate, and the like. The amount of the pH adjuster can be appropriately selected according to the set pH.

[0022] As the base, hydrocarbons such as liquid paraffin, squalane, petrolatum, gelled hydrocarbons (such as plastibase), ozokerite, α-olefin oligomer, and light liquid paraffin; silicone oils such as methylpolysiloxane, highly polymerized methylpolysiloxane, cyclic silicone, alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-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; fats and oils such as coconut oil, olive oil, rice bran oil, and shea butter; waxes such as jojoba oil, myrtle wax, candelilla wax, and lanolin; higher alcohols such as cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, octyldodecanol, isostearyl alcohol, phytosterol, and cholesterol; esters such as diisopropyl adipate, isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, and pentaerythrityl tetra(2-ethylhexanoate); polysaccharides such as dextrin and maltodextrin; lower alcohols such as ethanol and isopropanol; polyhydric alcohols such as glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, and polyethylene glycol (specifically, macrogol 200, macrogol 400, macrogol 1500, macrogol 4000, macrogol 6000, macrogol 20000, etc.); glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; water, etc. can be mentioned.Among these, from the viewpoint of the stability of vitamin A of the component (A), it is preferable to contain esters, and among them, isopropyl myristate and isopropyl palmitate are preferable. The esters are preferably contained in the external preparation for skin at 0.5 to 10% by mass, and more preferably 1 to 8% by mass.

[0023] Examples of the thickener include vinyl thickeners such as polyvinyl alcohol, polyvinyl pyrrolidone, and carboxyvinyl polymer; cellulose thickeners such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, and carboxyethyl cellulose; guar gum, pectin, pullulan, gelatin, locust bean gum, carrageenan, agar, xanthan gum, acrylic acid-methacrylic acid alkyl copolymer, bentonite, alginic acid, propylene glycol alginate, macrogol, sodium chondroitin sulfate, hyaluronic acid, sodium hyaluronic acid, (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymer, (ammonium acryloyldimethyltaurate / vinyl pyrrolidone) copolymer, and the like. From the viewpoint of usability among these, vinyl thickeners are more preferable.

[0024] Examples of the chelating agent include edetate salts such as disodium edetate, ethylenediaminetetraacetate, and sodium edetate; pyrophosphate; hexametaphosphate; citric acid; tartaric acid; gluconic acid, and the like.

[0025] Examples of the preservative include benzoic acids, parabens (methylparaben, ethylparaben, butylparaben), phenoxyethanol, dibutylhydroxytoluene, sorbic acid and its salts, boric acid, borax, and the like.

[0026] The coloring agent can be arbitrarily selected from coloring agents that can be used in external preparations (cosmetics, pharmaceuticals) such as acid dyes, basic dyes, oxidation dyes, and pigments. As for the fragrance, natural fragrances and synthetic fragrances can be used without particular limitation. For example, fragrances described in documents such as "Perfume and Flavor Chemicals" Vol.I and II (Steffen Arctander, Allured Pub.Co.(1994)), "Synthetic Perfume - Chemistry and Product Knowledge" (written by Motokazu Indoh, Chemical Industry Daily Press (1996)), "Perfume and Flavor Materials of Natural Origin" (Steffen Arctander, Allured Pub.Co.(1994)), "Encyclopedia of Scents" (edited by the Japan Flavor Association, Asakura Shoten (1989)), and "Flower oils and Floral Compounds In Perfumery" (Danute Lajaujis Anonis, Allured Pub.Co.(1993)) can be used. For example, plant-based fragrances such as peppermint oil, spearmint oil, jasmine oil, lemon oil, orange oil, lime oil, mandarin oil, rose oil, and rosemary oil can be mentioned as natural fragrances. Examples of synthetic fragrances include monoterpenes, diterpenes, sesquiterpenes, etc., specifically geraniol, linalool, citronellol, nerol, limonene, pinene, camphene, citral, citronellal, cineol, cumin, hinokic acid, hinokiol, phytol, etc.

[0027] [Manufacturing Method] The manufacturing method of the external preparation for skin of the present invention is not particularly limited, and for example, the following methods can be mentioned. (I) Add the component (B) and the water-soluble component to water, and heat at 60 - 70 °C to dissolve each component to prepare an aqueous phase. (II) Separately, mix the component (A) and the oily component, and heat at 60 - 70 °C to dissolve each component to prepare an oil phase. (III) Add and mix the oil phase heated and dissolved at 60 - 70 °C to the aqueous phase heated to 60 - 70 °C while stirring to obtain an oil-in-water (O / W type) emulsion. (IV) The obtained oil-in-water (O / W) emulsion is cooled to 30°C or lower and then the pH is adjusted to obtain an oil-in-water topical skin preparation composition.

[0028] [Oil-in-water topical skin preparation] The topical skin preparation of the present invention is an oil-in-water (O / W) emulsion, and the dosage form is not particularly limited, and examples include creams and milky lotions. Further, the topical skin preparation composition of the present invention has excellent bactericidal power against acne-related bacteria and Staphylococcus aureus, and is suitable as a medicine for treating acne and a medicine for treating eczema, and is particularly suitable as a medicine for treating acne.

[0029] There is no particular limitation on the viscosity of the topical skin preparation of the present invention, and it can be appropriately selected according to the purpose. However, the viscosity at 25°C is preferably 1 to 100 Pa·s, and more preferably 15 to 75 Pa·s. The viscosity is measured at 25°C for 1 minute under the condition of a rotation speed of 20 rpm using a BH-type viscometer (manufactured by Tokyo Keiki Co., Ltd.) and a No. 7 rotor.

[0030] The pH was measured with a pH meter (glass electrode type hydrogen ion concentration indicator, model HM-30R) manufactured by Toa DKK Corporation for a solution prepared by dissolving about 2 g of the topical skin preparation in 20 g of water. The pH of the topical skin preparation of the present invention is preferably 4 to 9, more preferably 6 to 8, and even more preferably 6.5 to 7.5 from the viewpoints of the stability of the component (A) and the suppression of skin irritation.

[0031] [Stabilization method] The present invention provides a method for stabilizing the above-mentioned component (A) by blending (B) an antioxidant in an oil-in-water topical skin preparation containing ibuprofen piconol (A). As shown in the examples described later, the stability of the component (A) over time can be obtained. The preferred components, contents, etc. are the same as those described above.

Examples

[0032] Hereinafter, examples and comparative examples will be shown to specifically explain the present invention, but the present invention is not limited to the following examples. In the following examples, unless otherwise specified, “%” of the composition indicates mass%, and the ratio indicates mass ratio.Note that Examples 2, 10, and 11 are reference examples.

[0033] [Examples, Comparative Examples] Skin external preparations having the compositions described in the following table were obtained by the following method. The following evaluations were performed on the obtained skin external preparations. The results are also shown in the table. (I) Preparation of Preliminary Preparation Liquid I (aqueous phase) A part of 1,3-butylene glycol was added to purified water, and component (B), sodium edetate, and carboxyvinyl polymer were added and swollen, and then dissolved by heating at 60°C (aqueous phase). (II) Preparation of Preliminary Preparation Liquid II (oil phase) The oil-soluble components (component (A), retinol palmitate, benzethonium chloride, isopropyl palmitate, POE(60) hydrogenated castor oil, dibutylhydroxytoluene, etc.) were sequentially mixed and dissolved by heating at 60°C. (III) Emulsification While stirring the aqueous phase prepared in I with a homogenizer, the oil phase prepared in II was added. After the addition was completed, it was stirred as it was for about 5 minutes to obtain an oil-in-water (O / W type) emulsion. (IV) pH adjustment The obtained oil-in-water (O / W type) emulsion was cooled until it reached 30°C or lower, and adjusted with sodium hydroxide to have the pH described in the following table to obtain a skin external preparation composition.

[0034] [Stability of Component (A)] 15 g of the skin external preparation composition was filled into an aluminum tube and stored under the conditions of 40°C for 6 months or 50°C for 10 weeks. After storage, the remaining amount of component (A) (ibuprofen piconol) was quantified according to the quantification method of "Ibuprofen Piconol" in the Seventeenth Revised Japanese Pharmacopoeia, and the residual rate with respect to the content immediately after production was calculated with the content immediately after production as 100% (rounded to the second decimal place).

[0035] [Color of Skin External Preparation] A cylindrical cap with a diameter of 100 mm and a height of about 50 mm was filled with about 0.3 g of a composition for external use on the skin. A cover glass was placed on it, and this cross-section was measured with a spectrocolorimeter (Konica Minolta Sensing Inc.). The evaluation of the color tone was based on the b value, which is an index of yellow - blue. * The values shown in the table are those immediately after production and after 10 weeks at 50°C.

[0036]

Table 1

[0037]

Table 2

[0038]

Table 3

[0039] The raw materials used in the above examples are shown below. Unless otherwise specified, the amounts of each component in the table are in terms of pure component. Ibuprofen piconol: Trade name "Ibuprofen piconol", manufactured by Kyoritsu Pharmaceutical Co., Ltd., conforming to the Japanese Pharmacopoeia Sodium pyrosulfite: Trade name "Sodium pyrosulfite (for manufacturing only)", manufactured by Fujifilm Wako Pure Chemical Corporation, conforming to the Japanese Pharmacopoeia Ascorbic acid: Trade name "L - Ascorbic acid", manufactured by Fuso Chemical Industry Co., Ltd., conforming to the Japanese Pharmacopoeia Glycine: Trade name "Glycine (for manufacturing only)", manufactured by Fujifilm Wako Pure Chemical Corporation, conforming to the Japanese Pharmacopoeia Benzethonium chloride: Trade name "Lonzagard Benzethonium Chloride - J", manufactured by Lonza Japan Ltd., conforming to the Japanese Pharmacopoeia Retinol palmitate: Trade name "Retinol palmitate 1.74 million IU / g", manufactured by DSM Nutrition Japan Co., Ltd., conforming to the Japanese Pharmacopoeia Tocopheryl Acetate: Trade name "Tocopherol Acetate", manufactured by DSM Nutritional Products Japan Ltd., conforming to the Japanese Pharmacopoeia Polysorbate 80: Trade name "Nikkol TO-10V", manufactured by Nikko Chemicals Co., Ltd. and Nippon Surfactant Industry Co., Ltd., conforming to the Japanese Pharmacopoeia Butylated Hydroxytoluene: Trade name "Butylated Hydroxytoluene", manufactured by Merck KGaA, conforming to the Pharmaceutical Additive Regulations Isopropyl Palmitate: Trade name "IPP-EX", manufactured by Nippon Surfactant Industry Co., Ltd., conforming to the Pharmaceutical Additive Regulations Polyoxyethylene Hydrogenated Castor Oil 60 (HCO-60): Trade name "HCO-60 (Pharmaceutical)", manufactured by Nippon Surfactant Industry Co., Ltd., conforming to the Pharmaceutical Additive Regulations Sodium Edetate: Trade name "Karest 2BST", manufactured by Chubu Karest Co., Ltd., conforming to the Japanese Pharmacopoeia 1,3-Butylene Glycol: Trade name "1,3-Butylene Glycol UK", manufactured by Daicel Corporation, conforming to the Pharmaceutical Additive Regulations Carboxyvinyl Polymer: Trade name "CARBOPOL 980", manufactured by IMCD Japan Co., Ltd., conforming to the Pharmaceutical Additive Regulations Sodium Hydroxide: Trade name "Sodium Hydroxide", manufactured by Kosakai Pharmaceutical Co., Ltd., conforming to the Japanese Pharmacopoeia

Claims

1. An oil-in-water type topical skin preparation containing (A) ibuprofen piconol and (B) one selected from sulfurous acid and its salts, thiosulfuric acid and its salts, and glycine and its salts, wherein the mass ratio in the topical skin preparation represented by (B) / (A) is 0.01 to 0.

5.

2. The topical skin preparation according to Claim 1, wherein the component (B) is selected from sodium pyrosulfite, potassium pyrosulfite, sodium sulfite, potassium sulfite, anhydrous sodium sulfite, sodium bisulfite, potassium bisulfite, sodium thiosulfate, potassium thiosulfate, and glycine.

3. An oil-in-water type topical skin preparation containing (A) ibuprofen piconol and (B) two or more selected from ascorbic acid and its salts, sulfurous acid and its salts, thiosulfuric acid and its salts, and glycine and its salts, wherein the mass ratio in the topical skin preparation represented by (B) / (A) is 0.002 to 0.

5.

4. The topical skin preparation according to Claim 3, wherein the component (B) is two or more selected from ascorbic acid, sodium ascorbate, potassium ascorbate, sodium ascorbate - 2 - sulfate, sodium pyrosulfite, potassium pyrosulfite, sodium sulfite, potassium sulfite, anhydrous sodium sulfite, sodium bisulfite, potassium bisulfite, sodium thiosulfate, potassium thiosulfate, and glycine.

5. The topical skin preparation according to Claim 3, wherein the component (B) contains one or more selected from ascorbic acid and its salts and one or more selected from sulfurous acid and its salts.

6. The topical skin preparation according to any one of Claims 1 to 5, wherein the content of the component (B) is 0.01% by mass or more in the topical skin preparation.

7. The topical skin preparation according to any one of Claims 1 to 6, wherein the pH is 4 to 9.

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