WO2022118942A1 - 乳剤性外用組成物 - Google Patents

乳剤性外用組成物 Download PDF

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WO2022118942A1
WO2022118942A1 PCT/JP2021/044378 JP2021044378W WO2022118942A1 WO 2022118942 A1 WO2022118942 A1 WO 2022118942A1 JP 2021044378 W JP2021044378 W JP 2021044378W WO 2022118942 A1 WO2022118942 A1 WO 2022118942A1
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Prior art keywords
weight
emulsion
oil
external composition
alcohol
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English (en)
French (fr)
Japanese (ja)
Inventor
智子 鈴木
まゆみ 前田
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Maruho Co Ltd
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Maruho Co Ltd
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Priority to EP21900691.3A priority Critical patent/EP4257127A4/en
Priority to JP2022566993A priority patent/JP7817187B2/ja
Priority to KR1020237017828A priority patent/KR20230116791A/ko
Priority to CN202180074975.7A priority patent/CN116528835A/zh
Priority to US18/250,330 priority patent/US20230390196A1/en
Publication of WO2022118942A1 publication Critical patent/WO2022118942A1/ja
Anticipated expiration legal-status Critical
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/327—Peroxy compounds, e.g. hydroperoxides, peroxides, peroxyacids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/06—Emulsions
    • A61K8/062—Oil-in-water emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/31—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/342—Alcohols having more than seven atoms in an unbroken chain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/38—Percompounds, e.g. peracids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin

Definitions

  • the present invention relates to a topical pharmaceutical composition useful for the treatment of acne vulgaris. More specifically, the present invention relates to an emulsion external composition for skin containing benzoyl peroxide.
  • Acne vulgaris is a skin disease that commonly occurs on the face, generally called "acne", and self-care by applying an external preparation is generally performed.
  • Benzoyl peroxide is used in the treatment of acne vulgaris in many countries, and for example, Patent Document 1 and Patent Document 2 disclose skin compositions containing benzoyl peroxide as an active ingredient.
  • the present invention provides a composition for skin containing benzoyl peroxide, which has few side effects of skin drying due to benzoyl peroxide and can keep benzoyl peroxide stable in the composition. The task is to do.
  • the present inventor has made an emulsion containing a specific amount of liquid oil and solid oil, an aqueous solvent, and a surfactant as a base of a composition containing benzoyl peroxide.
  • a sex base we have succeeded in providing a composition for skin having excellent moisturizing properties and stability of benzoyl peroxide.
  • the present invention relates to the following emulsion-based external composition.
  • the emulsion-based external composition according to [1] which contains only benzoyl peroxide as an active ingredient.
  • the liquid oil (B) is selected from the group consisting of squalane, liquid paraffin, light liquid paraffin, octyldodecyl myristate, decyl oleate, and cetyl 2-ethylhexanoate, [1] or [2].
  • the content of the liquid oil (B) is 0.5 to 10% by weight.
  • the content of the solid oil (C) is 0.3 to 1.4% by weight.
  • the emulsion-based external composition according to any one of [1] to [4].
  • the aqueous solvent (D) consists of (d1) 5 to 30% by weight of a polyhydric alcohol and (d2) 50% by weight or more of water.
  • Emulsified external composition As the liquid oil (B), 0.3 to 12.5% by weight of squalane, A fatty alcohol selected from the group consisting of stearyl alcohol, cetostearyl alcohol, and cetyl alcohol in an amount of 0.3 to 2.5% by weight as the solid oil (C).
  • the liquid oil (B) 1.5 to 5% by weight of squalane, A fatty alcohol selected from the group consisting of stearyl alcohol, cetostearyl alcohol, and cetyl alcohol in an amount of 0.3 to 0.9% by weight as the solid oil (C).
  • the aqueous solvent (D) contains (d1) 10 to 25% by weight of a polyhydric alcohol and (d2) 65% by weight or more of water, and the total content of components other than the components [A] to [E] is 5.
  • the emulsion-based external composition according to the present invention has excellent moisturizing properties, the skin at the application site is less likely to dry, and the active ingredient benzoyl peroxide is also excellent in stability.
  • FIG. 1 is a diagram for explaining a water transpiration suppression evaluation test.
  • the emulsion composition for external use of the present invention contains benzoyl peroxide (A) as an active ingredient.
  • Benzoyl peroxide can be prepared by adding a hydrogen peroxide solution to a sodium hydroxide solution to obtain a sodium peroxide solution, and adding benzoyl chloride to the solution. It can also be obtained from the market.
  • the content of benzoyl peroxide is preferably 1 to 5% by weight, more preferably 1.5 to 4% by weight, particularly preferably 2 to 3% by weight, still more preferably 2.5% by weight.
  • the weight% or the content ratio means the ratio of the weight of each component when the total weight of the emulsion-based external composition is 100%.
  • Benzoyl peroxide (A) is preferably not coated with a metal oxide layer. Further, it is desirable that the emulsion composition for external use of the present invention contains only benzoyl peroxide as an active ingredient (ingredient for treating acne).
  • a combination drug containing a naphthoic acid compound such as adapalene and benzoyl peroxide as an active ingredient is known, but the emulsion-based external composition of the present invention is a naphthoic acid compound such as adapalene. It is preferable not to contain.
  • the emulsion-based external composition of the present invention contains 0.3 to 12.5% by weight of the liquid oil (B) having an ⁇ value of 0 ° to 8 °.
  • the liquid oil refers to an oily component that is liquid at room temperature (25 ° C.).
  • the ⁇ value means the ⁇ value according to the organic conceptual diagram.
  • the organic conceptual diagram was proposed by Akira Fujita, and the details are described in "Pharmaceutical Bulletin", 1954, vol. 2, 2, pp. 163-173; “Chemistry”, 1957, vol.11, 10, pp.719-725; “Fragrance Journal", 1981, vol.50, pp.79-82, etc.
  • the source of all organic compounds is methane (CH 4 ), and all other compounds are regarded as derivatives of methane, and constant values are set for their carbon number, substituent, transformation part, ring, etc. Scores are added to obtain organic and inorganic values. The slope when this value is plotted on a diagram with the organic value on the X-axis and the inorganic value on the Y-axis, and the angle thereof is the ⁇ value.
  • liquid oil having an ⁇ value of more than 8 ° is used, the stability of benzoyl peroxide in the emulsion-based external composition tends to deteriorate. It is more preferable to use a liquid oil having an ⁇ value of 7 ° or less.
  • liquid oil (B) examples include liquid hydrocarbons and low-polarity fatty acid ester oils.
  • liquid hydrocarbons include squalane (0 °), liquid paraffin (0 °), light liquid paraffin (0 °), light isoparaffin (0 °), liquid isoparaffin (0 °), squalene (1 °), ⁇ . -Olefin oligomers (0 °), polybutene (0 °) and the like can be mentioned.
  • low-polarity fatty acid ester oil examples include octyldodecyl myristate (5 °), oleyl oleate (5 °), decyl oleate (6 °), cetyl 2-ethylhexanoate (7 °) and the like.
  • the numerical value in parentheses following each substance name represents the ⁇ value.
  • Any of the above liquid oils can be used alone or in combination. More preferred liquid oils are liquid hydrocarbon oils such as squalane, liquid paraffin and light liquid paraffin having an ⁇ value of 0 °, with squalane being particularly preferred.
  • the content of the liquid oil (B) is preferably 0.5 to 10% by weight, more preferably 1 to 8% by weight, particularly preferably 1.5 to 5% by weight, still more preferably 2 to 4% by weight. Too little liquid oil reduces the moisturizing ability, while too much liquid oil reduces the stability of benzoyl peroxide.
  • the emulsion composition for external use of the present invention contains 0.3 to 2.5% by weight of the solid oil (C).
  • solid oil refers to semi-solid or solid oily components at room temperature (25 ° C).
  • Preferred examples of the solid oil (C) include aliphatic alcohols having 16 or more carbon atoms, fatty acids having 18 or more carbon atoms, hydrocarbons, waxes and the like.
  • aliphatic alcohol having 16 or more carbon atoms a saturated fatty alcohol having 16 to 22 carbon atoms (more preferably 16 to 20 carbon atoms, particularly preferably 16 to 18 carbon atoms) having one hydroxyl group only in the terminal carbon.
  • Alcohols (particularly linear ones) are mentioned, and particularly preferable examples are stearyl alcohol (18 carbon atoms), cetanol (also referred to as cetyl alcohol: 16 carbon atoms), and cetostearyl alcohol (almost equal to stearyl alcohol and cetanol). Amount mixture).
  • any of the above solid oils can be used alone or in combination.
  • the fatty acid having 18 or more carbon atoms include stearic acid (18 carbon atoms) and behenic acid (22 carbon atoms).
  • the hydrocarbon include paraffin, microcrystalline wax and the like.
  • the waxes include bleached beeswax, lanolin and the like.
  • the content of the solid oil (C) is more preferably 0.3 to 2% by weight, particularly preferably 0.3 to 1.4% by weight, and even more preferably 0.3 to 0.9% by weight.
  • the amount of the solid oil (C) increases, the moisturizing property of the emulsion-based external composition increases, but on the other hand, the stability of benzoyl peroxide decreases.
  • the emulsion-based external composition of the present invention is characterized by containing a specific amount of liquid oil and a specific amount of solid oil in combination.
  • the total amount of the liquid oil and the solid oil is preferably at least 0.6% by weight, more preferably 1.0% by weight or more, particularly preferably 1.5% by weight or more, and further preferably 2.4% by weight or more. preferable.
  • the total amount of the liquid oil and the solid oil is preferably 12% by weight or less, more preferably 10% by weight or less, particularly preferably 8% by weight or less, and further preferably 6% by weight or less.
  • the emulsion-based external composition of the present invention contains an aqueous solvent (D).
  • aqueous solvent include water (preferably purified water) and polyhydric alcohols.
  • polyhydric alcohols include polyhydric alcohols having 3 to 6 carbon atoms.
  • Polyhydric alcohols selected from glycerin, propylene glycol, and 1,3-butylene glycol are more preferred, with glycerin and 1,3-butylene glycol particularly preferred. Any of the above aqueous solvents can be used alone or in combination.
  • the content of the aqueous solvent (D) is preferably 60% by weight or more, more preferably 70% by weight or more, particularly preferably 80% by weight or more, still more preferably 85% by weight or more.
  • the upper limit of the aqueous solvent (D) is preferably 97% by weight or less, more preferably 95% by weight or less.
  • the emulsion external composition preferably contains (d1) a polyhydric alcohol and (d2) water (preferably purified water) as the aqueous solvent (D), and 5 to 30% by weight of the polyhydric alcohol. And 50% by weight or more of water, more preferably 10 to 25% by weight of polyhydric alcohol, and 65% by weight or more of water, particularly preferably 10 to 20% by weight of polyhydric alcohol, and 70. It is more preferable to contain water in an amount of% by weight or more.
  • the upper limit of water (d2) is preferably 95% by weight or less, more preferably 90% by weight or less, particularly preferably 85% by weight or less, and even more preferably 80% by weight or less.
  • the weight% of the above (d1) and (d2) means not the total amount of the aqueous solvent (D) but the weight% when the total amount of the emulsion-based external composition is 100% by weight.
  • a lower monohydric alcohol (a monohydric alcohol having 1 to 3 carbon atoms such as ethanol and isopropanol) may be used as the aqueous solvent (D), but the lower monohydric alcohol has irritation to the skin.
  • the emulsion-based external composition of the present invention preferably contains substantially no lower monohydric alcohol.
  • substantially free of a substance means that the substance was not intentionally added at the time of preparation of the emulsion-based external composition, and therefore, in the emulsion-based external composition.
  • the content of the substance is usually less than 1% by weight, more preferably less than 0.5% by weight, and particularly preferably 0% by weight.
  • the emulsion-based external composition of the present invention contains a surfactant (E).
  • a surfactant examples include nonionic surfactants, cationic surfactants, anionic surfactants, and amphoteric surfactants.
  • nonionic surfactants are polyethylene glycol fatty acid esters such as polyethylene glycol monostearate, ethylene glycol monostearate, polyethylene glycol monolaurate, ethylene glycol monostearate, and polyethylene glycol monooleate; polyoxyethylene.
  • Polyoxyethylene alkyl ethers such as behenyl ethers, polyoxyethylene oleyl ethers, polyoxyethylene octyldodecyl ethers, polyoxyethylene cetyl ethers, polyoxyethylene stearyl ethers, and polyoxyethylene lauryl ethers; polyoxyethylene alkylphenol ethers; poly Oxyethylene cured castor oil; glycerin fatty acid esters such as glyceryl monostearate, glyceryl monostearate, self-emulsifying glyceryl monostearate, glyceryl myristate, glyceryl monoisostearate, and glyceryl monooleate; Polyglycerin fatty acid esters such as polyglyceryl monostearate, polyglyceryl monooleate, polyglyceryl monolaurate, polyglyceryl monomyristate, and decaglyceryl pentastearate; sorbitan monopal
  • Polysorbate fatty acid esters such as sorbitan, sorbitan tristearate, and sorbitan trioleate
  • polyoxyethylene sorbitan fatty acid esters such as polysorbate 60, polysorbate 65, polysorbate 80, and polysorbate 85
  • polyoxyethylene polyoxypropylene alkyl ethers such as polyoxyethylene polyoxypropylene cetyl ether (20E.O.) (8P.O.);
  • Examples thereof include oxyethylene beeswax derivatives.
  • cationic surfactants include cetyltrimethylammonium chloride, lauryldimethylbenzylammonium chloride, tetrabutylammonium chloride, dioctadecyldimethylammonium chloride and the like.
  • anionic surfactants include sodium alkylbenzene sulfonate, sodium dodecyl sulphate, sodium coconut alcohol ethoxysulfate, sodium ⁇ -olefin sulfonate, emulsified cetostearyl alcohol and the like.
  • amphoteric tensides examples include N-alkyl-N, N-dimethylammonium betaine, imidazoline-type amphoteric tensides, and the like.
  • surfactants (E) can be used alone or in combination.
  • Preferred surfactants are nonionic surfactants, with polyethylene glycol fatty acid esters being more preferred.
  • the emulsion composition for external use of the present invention may contain polyoxyethylene alkyl ether (nonionic surfactant), but polyoxyethylene araquil ether (polyoxyethylene and 20 carbon atoms). It is preferable that the ether composed of arachidyl alcohol, which is an aliphatic alcohol, is substantially not contained.
  • the content of the surfactant (E) is preferably 0.05 to 2% by weight, more preferably 0.1 to 1% by weight, and particularly preferably 0.2 to 0.5% by weight.
  • the emulsion-based external composition of the present invention may contain one or more components other than the above (A) to (E), but the total amount of these components is preferably 5% by weight or less, more preferably 3% by weight or less. It is preferable, and 2% by weight or less is particularly preferable.
  • the emulsion-based external composition of the present invention comprises a polyurethane polymer-type compound or a derivative thereof, a naphthoic acid derivative such as adaparene, polyoxyethylene araquil ether, and a non-irritating benzoic acid ester (C 12 to C 15 alkyl benzoate, etc.).
  • a substance selected from the group consisting of a film-forming agent polyvinylpyrrolidone, etc.
  • a film-forming agent polyvinylpyrrolidone, etc.
  • the pH value of the emulsion-based external composition of the present invention is preferably 3 to 7. If the pH is less than 3, it is irritating to the skin, and if it exceeds 7, the stability of benzoyl peroxide deteriorates. A more preferable pH value is 4 to 6, and a particularly preferable pH value is 4 to 5.
  • the pH adjusting agent include diisopropanolamine, triisopropanolamine, triethanolamine, potassium hydroxide, sodium hydroxide, sodium citrate, phosphoric acid, tartrate acid, dl-apple acid, glacial acetic acid and the like. All of the above pH regulators can be used alone or in combination.
  • the emulsion composition for external use of the present invention may contain a thickener.
  • the thickener include carboxyvinyl polymer, carboxymethyl cellulose and the like, and carboxyvinyl polymer is particularly preferable.
  • the content of the thickener is preferably 0.2 to 1.5% by weight, more preferably 0.3 to 1.0% by weight, and particularly preferably 0.4 to 0.8% by weight.
  • the emulsion-based external composition of the present invention can contain other additives generally used for external skin preparations.
  • additives include antioxidants (ascorbic acid, dibutylhydroxytoluene, ⁇ -tocopherol, tocophenol acetate, etc.), stabilizers (sodium edetate hydrate, 1-menthol, etc.), preservatives (preservatives, etc.). Paraoxybenzoic acid ester, phenoxyethanol, etc.), colorants (titanium oxide, etc.) and the like can be mentioned.
  • Examples of the dosage form of the emulsion-type external composition of the present invention include an emulsion lotion, a water-in-oil (W / O-type) cream, an oil-in-water (O / W) cream, and an external aerosol.
  • Examples include pump sprays.
  • an emulsion lotion (emulsion type liquid composition) is preferable.
  • the emulsion lotion is an oil-in-water (O / W type) liquid composition obtained by emulsifying an oily component (a component that does not mix with water) and an aqueous component (a component that mixes with water and water) with a surfactant. It is a thing.
  • the emulsion lotion contains oil, it has higher moisturizing property than the aqueous gel agent which does not contain oil component.
  • the aqueous gel agent which does not contain oil component.
  • it since it is liquid and has low viscosity, it has a refreshing feel and is less likely to cause stickiness or shine on the application site, so it is suitable for application to the face, which is a frequent site of acne vulgaris.
  • Benzoyl peroxide (A) Benzoyl peroxide, (B) 0.3 to 12.5% by weight (preferably 0.5 to 10% by weight, more preferably 1 to 8% by weight, particularly preferably 1.5 to 5% by weight, still more preferably 2 to 4% by weight. %), At least one liquid oil selected from the group consisting of squalane, liquid paraffin, light liquid paraffin, octyldodecyl myristate, decyl oleate, and cetyl 2-ethylhexanate.
  • (C) 0.3 to 2.5% by weight preferably 0.3 to 2.0% by weight, more preferably 0.3 to 1.4% by weight, particularly preferably 0.3 to 0.9% by weight). , More preferably 0.4 to 0.9% by weight
  • at least one solid oil selected from the group consisting of aliphatic alcohols having 16 or more carbon atoms, stearic acid, paraffin, and sardine wax.
  • (D) (d1) 5 to 30% by weight (preferably 10 to 25% by weight, more preferably 10 to 20% by weight) polyhydric alcohol, and (d2) 50% by weight or more (preferably 65% by weight or more, More preferably 70% by weight or more), an aqueous solvent consisting of water, (E)
  • examples thereof include an emulsion-type external composition (particularly, an emulsion-type lotion) containing at least one surfactant.
  • an emulsion external composition having a total content of components other than (A) to (E) of 5% by weight or less, 3% by weight or less, or 2% by weight or less is preferable.
  • Benzoyl peroxide (A) Benzoyl peroxide, (B) 0.3 to 12.5% by weight (preferably 0.5 to 10% by weight, more preferably 1 to 8% by weight, particularly preferably 1.5 to 5% by weight, still more preferably 2 to 4% by weight. %), Squalan, (C) 0.3 to 2.5% by weight (preferably 0.3 to 2.0% by weight, more preferably 0.3 to 1.4% by weight, particularly preferably 0.3 to 0.9% by weight). , More preferably 0.4-0.9% by weight), at least one solid oil selected from the group consisting of stearyl alcohol, cetostearyl alcohol, and cetyl alcohol.
  • (D) (d1) 5 to 30% by weight (preferably 10 to 25% by weight, more preferably 10 to 20% by weight) selected from the group consisting of glycerin, 1,3-butylene glycol, and propylene glycol.
  • An aqueous solvent consisting of polyhydric alcohol and (d2) 50% by weight or more (preferably 65% by weight or more, more preferably 70% by weight or more) water.
  • Examples thereof include an emulsion-type external composition (particularly, an emulsion-type lotion) containing at least one surfactant.
  • an emulsion external composition having a total content of components other than (A) to (E) of 5% by weight or less, 3% by weight or less, or 2% by weight or less is preferable.
  • the emulsion composition for external use of the present invention can be used for the treatment of acne.
  • the amount and frequency of application may be appropriately adjusted according to the degree of symptoms, the concentration of benzoyl peroxide in the emulsion composition for external use, and the like. For example, when used on the face, once or twice a day, after washing the face, apply an amount covering the affected area to the skin with acne vulgaris.
  • compositions of the present invention include compositions obtained by arbitrarily combining them.
  • a composition obtained by arbitrarily combining the contents of each component is also included.
  • the numerical range relating to each component, pH, etc. can be arbitrarily combined, and when a plurality of numerical ranges are described, the upper limit value or the lower limit value of each numerical range can be arbitrarily combined.
  • % For each component in the examples means% by weight.
  • surfactant a nonionic surfactant was used.
  • Example 1 Each pharmaceutical product (emulsible lotion) having the compositions shown in Tables 1 and 2 was prepared. Then, in order to evaluate the moisturizing property, the water evaporation suppression rate was measured for each pharmaceutical product by the method shown below. A product with a moisture transpiration suppression rate of 25% or more is evaluated to maintain a moist feeling (high moisturizing property) after the formulation is applied when a sensory test is performed using a human as a panelist. Was evaluated as "good” for moisturizing ability, and less than 25% was evaluated as “poor” for moisturizing ability.
  • ⁇ Measurement of water evaporation suppression ability> A circle with a diameter of 4 cm was opened in the center of the plastic cup lid, and a carrier membrane was attached to this portion (see FIG. 1). After placing this lid on a cup containing 50 g of water, 100 ⁇ L (about 0.1 g) of the pharmaceutical product was applied to the carrier membrane. In addition, as a comparison target, a carrier membrane to which no preparation was applied was used. As the carrier film, a membrane filter made of hydrophobic polytetrafluoroethylene manufactured by Millipore (pore diameter 10 ⁇ m, diameter 47 mm) was used.
  • the amount of water evaporated from the cup of the preparation-coated group through the carrier membrane was defined as WL X (g / h), and the water content was evaporated from the cup of the preparation-uncoated group through the carrier membrane.
  • the water content was set to WL 0 (g / h), and the water transpiration suppression rate (%), which is a value indicating the blocking effect, was calculated using the following formula.
  • the numerical value of each component shown in Table 1 is% by weight, and the blank means 0%.
  • the "appropriate amount" of purified water means the amount of purified water in which the total amount of the pharmaceutical product is 100% by weight (the same applies to the other tables).
  • the pharmaceutical product 1 having 0% solid oil or the pharmaceutical product 2 having 0.25% solid oil had a low water transpiration suppression rate, and sufficient moisturizing ability could not be obtained.
  • the formulations 3 to 5 having a solid oil content of 0.5 to 1.8% had good moisturizing properties.
  • the formulations 6 and 7 (without solid oil) having a large amount of polyhydric alcohol showed a higher water transpiration suppression rate than the preparation 1, but did not reach 25%.
  • the pharmaceutical product 8 having a smaller amount of polyhydric alcohol than the pharmaceutical product 3 showed good moisturizing ability.
  • the preparation containing a predetermined amount of solid oil shows high moisturizing ability, but the preparation containing no solid oil is desired even if it contains a large amount of glycerin generally known as a moisturizer. It turned out that the moisturizing ability could not be achieved.
  • the formulations (formations 8A to C) containing 0.5% or more of solid oil and increasing the amount of solid oil and liquid oil also showed a water evaporation suppression rate of 30% or more and had a high moisturizing ability.
  • Table 2 shows the results of changing the type of solid oil.
  • Example 2 Each pharmaceutical product (emulsible lotion) having the compositions shown in Tables 3 to 5 was prepared and tested for the stability of benzoyl peroxide as an active ingredient. After storage at 50 ° C. for 2 weeks, a formulation having a content of benzoic acid, which is a decomposition product of benzoyl peroxide, of 10% or less is evaluated as "good", and a formulation exceeding 10% is evaluated as "poor”. I evaluated it.
  • the method of the stability test is as follows.
  • ⁇ Stability test method> An amount corresponding to about 50 mg of benzoyl peroxide was weighed, and tetrahydrofuran and acetonitrile were added for dispersion extraction. Tetrahydrofuran was further added to the extract and then filtered to obtain a sample solution. Separately, about 0.1 g of benzoic acid was weighed and acetonitrile was added to prepare a standard solution. The sample solution and the standard solution were tested by liquid chromatography, and the amount of benzoic acid contained in the preparation was measured.
  • Test conditions ⁇ br /> Detector Ultraviolet absorptiometer (measurement wavelength: 235 nm) Column: A stainless steel tube with an inner diameter of 4.6 mm and a length of 15 cm filled with octadecylsilylated silica gel for liquid chromatography of 5 ⁇ m
  • Mobile phase A Water / acetic acid (100) mixed solution (1000: 1)
  • Mobile phase B Acetonitrile / acetic acid (100) mixed solution (1000: 1)
  • the concentration gradient is controlled from the mobile phase A rich to the mobile phase B rich by changing the mixing ratio of the mobile phase A and the mobile phase B.
  • the stability of benzoyl peroxide tends to decrease as the amount of solid oil increases (formulations 33 to 36), and when the amount of solid oil reaches 3% (formulation 36), the desired stability is observed.
  • the formulations having 1% or less of solid oil showed the desired stability even when the liquid oil was increased to 6%.
  • the formulations having a small amount of solid oil had a benzoic acid content of less than 5%, showing extremely high stability.
  • Example 3 Each preparation (emulsible lotion) having different amounts of solid oil and liquid oil was prepared, and a moisturizing ability test and a stability test were carried out. The results are shown in Table 6. Each test method is as described in Example 1 and Example 2.
  • Example 4 Preparations (emulsified lotions) with different types of solid oil were prepared and stability tests were conducted. The results are shown in Table 7. The test method is as described in Example 2.
  • Example 5 Preparations (emulsified lotions) with different types of liquid oil were prepared and a moisturizing ability test was conducted. The results are shown in Table 8. The test method is as described in Example 1.
  • the desired moisturizing ability could be achieved even when a liquid oil having an ⁇ value of 0 °, 5 °, or 7 ° was used.

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JPH01268632A (ja) * 1988-03-09 1989-10-26 L'oreal Sa 組成物
JPH0987140A (ja) 1995-04-14 1997-03-31 Imaginative Res Assoc Inc 過酸化ベンゾイル組成物
US20060135822A1 (en) * 2004-12-21 2006-06-22 Alpharx Inc. Stabilization of benzoyl peroxide in solution
JP2007009199A (ja) * 2005-06-03 2007-01-18 Maruho Co Ltd 液晶乳化型組成物
JP2010513427A (ja) * 2006-12-21 2010-04-30 ガルデルマ・リサーチ・アンド・デヴェロップメント 少なくとも１種のレチノイドおよび過酸化ベンゾイルを含むエマルジョン
JP2013241469A (ja) 2006-11-28 2013-12-05 Galderma Research & Development 過酸化ベンゾイル、少なくとも１種のナフトエ酸誘導体および少なくとも１種のポリウレタンポリマー型の化合物またはその誘導体を含む組成物ならびにそれらの使用
WO2017068673A1 (ja) * 2015-10-21 2017-04-27 マルホ株式会社 皮膚用の医薬組成物

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EP1898898A2 (en) 2005-03-10 2008-03-19 Jr Chem, LLC Benzoyl peroxide compositions and methods of use
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JPH01268632A (ja) * 1988-03-09 1989-10-26 L'oreal Sa 組成物
JPH0987140A (ja) 1995-04-14 1997-03-31 Imaginative Res Assoc Inc 過酸化ベンゾイル組成物
US20060135822A1 (en) * 2004-12-21 2006-06-22 Alpharx Inc. Stabilization of benzoyl peroxide in solution
JP2007009199A (ja) * 2005-06-03 2007-01-18 Maruho Co Ltd 液晶乳化型組成物
JP2013241469A (ja) 2006-11-28 2013-12-05 Galderma Research & Development 過酸化ベンゾイル、少なくとも１種のナフトエ酸誘導体および少なくとも１種のポリウレタンポリマー型の化合物またはその誘導体を含む組成物ならびにそれらの使用
JP2010513427A (ja) * 2006-12-21 2010-04-30 ガルデルマ・リサーチ・アンド・デヴェロップメント 少なくとも１種のレチノイドおよび過酸化ベンゾイルを含むエマルジョン
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See also references of EP4257127A4

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WO2025142990A1 (ja) * 2023-12-26 2025-07-03 マルホ株式会社 皮膚用組成物

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