WO2022163694A1 - 外用剤組成物 - Google Patents

外用剤組成物 Download PDF

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Publication number
WO2022163694A1
WO2022163694A1 PCT/JP2022/002876 JP2022002876W WO2022163694A1 WO 2022163694 A1 WO2022163694 A1 WO 2022163694A1 JP 2022002876 W JP2022002876 W JP 2022002876W WO 2022163694 A1 WO2022163694 A1 WO 2022163694A1
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Prior art keywords
less
mass
component
composition
external preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
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PCT/JP2022/002876
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English (en)
French (fr)
Japanese (ja)
Inventor
崇志 内田
信 野原
江美 大久保
信三 大隅
亮介 藤井
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Kao Corp
Original Assignee
Kao Corp
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Filing date
Publication date
Application filed by Kao Corp filed Critical Kao Corp
Priority to US18/262,942 priority Critical patent/US20240115528A1/en
Priority to CN202280010411.1A priority patent/CN116723865A/zh
Priority to EP22745913.8A priority patent/EP4285931A4/en
Publication of WO2022163694A1 publication Critical patent/WO2022163694A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K8/042—Gels
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • 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
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/618—Salicylic acid; Derivatives thereof having the carboxyl group in position 1 esterified, e.g. salsalate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/534—Mentha (mint)
    • 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
    • A61K47/14—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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K8/046—Aerosols; Foams
    • 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
    • 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
    • A61K8/345—Alcohols containing more than one hydroxy group
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8129—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers or esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers, e.g. polyvinylmethylether
    • 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
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61K9/12—Aerosols; Foams
    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
    • 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 an external preparation composition.
  • a liquid skin external preparation and patch containing medicinal ingredients such as antiphlogistic and analgesic ingredients and bactericidal and antiseptic ingredients are known.
  • existing liquid external preparations for skin have problems such as being easy to rub off with clothes after being applied to the skin, and that it is difficult to continuously release the medicinal ingredients to the skin.
  • a patch containing a medicinal ingredient does not conform well to the skin and is easily peeled off, it becomes difficult to continuously release the medicinal ingredient to the skin.
  • a patch having high adhesiveness to the skin also has a problem of increasing the burden on the skin when it is peeled off from the skin.
  • patches have problems in actual use, such as rashes easily and appearance when applied to the skin is a concern.
  • Film-forming formulations that can continuously release medicinal ingredients to the skin are being studied.
  • Film-forming preparations can form a film when applied to the skin, and therefore are less likely to rub off compared to liquid external skin preparations. It is also preferable in that it does not stand out like a patch when applied to the skin, and less burden on the skin when it is removed from the skin.
  • Patent Document 1 Japanese National Publication of International Patent Application No. 2009-519956 describes an adhesive solid formulation for skin delivery of a drug, comprising: a drug; a volatile solvent system containing a volatile solvent; a solvent vehicle comprising a volatile solvent system; and a solidifying agent; and having a viscosity suitable for application and adhesion to the skin surface prior to evaporation of the volatile solvent system, and applied to the skin surface.
  • the formulation forms a solidified layer after at least partial evaporation of the volatile solvent system, the drug being continuously delivered to the skin after at least substantial evaporation of the volatile solvent system, provided that at least two volatile Formulations have been proposed in which there is a solvent, two non-volatile solvents, or two solidifying agents.
  • the formulation can provide sustained drug delivery over an extended period of time, is not susceptible to unintentional removal by contact with clothing, other objects, or people during the duration of the application time, and is compatible with the skin. It is described as being able to be applied to skin areas subject to stretching and stretching without causing discomfort or poor contact, and to be easily removed after application and use.
  • Patent Document 2 Japanese National Publication of International Patent Application No. 2014-515365 describes an ethyl acrylate/methyl methacrylate copolymer; ethanol, isopropanol or a mixture thereof; water; and at least one physiologically active agent; have been proposed for transdermal administration of The composition is described as a film-forming composition that rapidly forms a non-sticky, durable and very soft film.
  • the present invention relates to the following.
  • [1] Contains (A) a medicinal ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent and (E) water, and has a viscosity of 1.0 mPa s or more at 25°C.
  • An external preparation composition having a viscosity of 10,000 mPa ⁇ s or less.
  • Lotion formulations, gel formulations, ointment formulations, cream formulations, or foam formulations comprising the external preparation composition according to [1] above.
  • [4] Contains (A) a medicinal ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, and has a viscosity of 1.0 mPa s at 25 ° C.
  • a method of using an external preparation composition comprising the steps of applying an external preparation composition having a viscosity of 10,000 mPa ⁇ s or more to the skin and then drying the composition.
  • a method for producing a film comprising the step of directly applying or spraying the composition for external use according to [1] above to the skin.
  • the present invention contains (A) a medicinal ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, and has a viscosity of 1.0 mPa ⁇ at 25°C. s or more and 10,000 mPa ⁇ s or less.
  • the composition is also referred to as "the composition of the present invention” as appropriate.
  • the term “external preparation composition” refers to a composition that is mainly applied to the skin surface.
  • water-insoluble polymer means that 1 g of the polymer is immersed in 10 g of ion-exchanged water at 23° C. and 1 atm, and after 24 hours, more than 0.5 g of the immersed polymer does not dissolve. It means something that has a property.
  • non-volatile base means that 1 g of the base is spread on a glass petri dish with a diameter of 48 mm and left at 25 ° C. and normal pressure for 24 hours. It refers to the base that exhibits.
  • Volatile solvent means that 1 g of the solvent is spread on a glass petri dish with a diameter of 48 mm, and the mass reduction rate after standing at 25 ° C. and normal pressure for 24 hours is 1% or more, and is liquid at 25 ° C. and other than water. means a component of In this specification, the resistance of the coating to perspiration, humidity, etc. (moisture resistance) and the resistance to rubbing off of the coating (scratch resistance) are collectively referred to as “durability of the coating”.
  • composition of the present invention comprises component (A): medicinal component, component (B): water-insoluble polymer, component (C): nonvolatile base, component (D): volatile base, and component (E ): contains water, but component (A) is a component that is not contained in any of component (B), component (C), and component (D), and component (B) is a component (C) and component (D).
  • Patent Literatures 1 and 2 there is room for improvement with regard to sustained sustained release of drugs, physiologically active agents, and the like to the skin.
  • the present invention can continuously release a medicinal ingredient to the skin, has good film-forming properties, has high applicability to the skin, has high quick-drying properties, and has an effect of suppressing the stickiness and tightness of the formed film.
  • the present invention relates to an external preparation composition which is excellent in appearance and durability of the film.
  • the present inventors have found that an external preparation composition containing a medicinal ingredient, a water-insoluble polymer, and a prescribed solvent component and having a prescribed viscosity can solve the above problems.
  • a medicinal ingredient can be continuously and slowly released to the skin, the film-forming property is good, the applicability to the skin and quick-drying property are high, and stickiness and tightness of the formed film are suppressed. It is possible to provide an external preparation composition excellent in efficacy, appearance and durability of the film, a formulation using the same, a method for using the external preparation composition, and a method for producing a film.
  • the composition of the present invention is a film-forming composition containing, as film-forming components, a water-insoluble polymer as component (B) and a non-volatile base as component (C).
  • component (B) a water-insoluble polymer
  • component (C) a non-volatile base
  • component (A) when a highly crystalline component such as felbinac, which will be described later, is used as the medicinal component (A), if the compatibility between component (A) and the coating is low, component (A) will crystallize in the coating. and the sustained release to the skin is reduced. However, even if the compatibility between the component (A) and the film is too high, it is considered that the component (A) is taken into the film and is difficult to be released to the skin in a sustained manner. When the water-insoluble polymer of component (B) is used as the film-forming component, the compatibility between the film and component (A) may be excessively high or low, and the sustained release of component (A) may be reduced. it is conceivable that.
  • component (C) reduces the compatibility between the coating and component (A) when the compatibility between the coating and component (A) is excessively high, or reduces the compatibility of the coating with component (A).
  • compatibility between and component (A) is low, it is thought that the compatibility is improved to suppress crystallization of component (A), thereby improving the sustained release of component (A).
  • component (B) since the component (B) is water-insoluble, it can form a highly hydrophobic film, which prevents the film from rubbing off due to sweat, humidity, etc.
  • component (B) and (C) due to the synergistic effect of the components (B) and (C), it has high applicability to the skin, quick drying, no stickiness and tautness, good appearance, and is resistant to rubbing off after application to the skin and has good durability. It is thought that a composition capable of forming a fine film can be obtained. It is believed that component (D) contributes to improving the composition's coatability, quick-drying property, storage stability, etc., and component (E) contributes to improving the storage stability of the composition.
  • the composition of the present invention contains the components (D) and (E) and has a viscosity within a predetermined range, so that the composition is easily compatible with the skin, and has excellent film-forming properties, durability of the film, and applicability. and quick-drying properties can be compatible, and as a result, it is thought that the component (A) can be effectively and sustainedly released onto the skin.
  • component (A) Medicinal ingredient>
  • the composition of the present invention contains a medicinal ingredient as component (A).
  • component (A) is preferably a skin external drug component that can be transdermally administered.
  • component (A) is a group consisting of an anti-inflammatory analgesic component, a local stimulating component, a blood circulation promoting component, an antihistamine component, a crude drug component, an antipruritic component, a local anesthetic component, a keratin softening component, a bactericidal component, and an antibacterial component. It is preferable to include one or more selected from.
  • Anti-inflammatory and analgesic ingredients include glycol salicylate, methyl salicylate, aspirin, sulpyrin hydrate, acetaminophen, diclofenac sodium, fenbufen, ibuprofen, aminoprofen, loxoprofen sodium or its hydrate, naproxen, oxaprofen, ketoprofen, tiaprofenic acid, sulindac, aluminum flufenamate, felbinac, mefenamic acid, indomethacin, indomethacin farnesyl, acemethacin, progglutetacin maleate, bendazac, piroxicam, ampiroxicam, lornoxicam, tenoxicam, meloxicam, etodolac, tiaramide hydrochloride, bucolome, Flurbiprofen, esflurbiprofen, lysozyme hydrochloride, bromelain, diphenhydr
  • Local stimulating ingredients include l-menthol, dl-camphor, nonylic acid vanillylamide, ammonia, and peppermint oil.
  • Blood circulation-promoting ingredients include benzyl nicotinate, sodium polyethylene sulfonate, and tocopherol acetate.
  • Antihistamine components include diphenhydramine, diphenhydramine hydrochloride, diphenhydramine salicylate, chlorpheniramine maleate, and the like.
  • Herbal ingredients include pepper, eucalyptus oil, Phellodendron bark, arnica tincture, juniper, peony, mugwort, cinnamon, cnidium, kobus, sojutsu, radish, matsubusa, chimp, carrot, tuna, clove, ginger, Sanshishi, licorice, fennel , Mokutsu, Kouka, Koboku, Spruce, Inch and the like.
  • Antipruritic ingredients include crotamiton, cortisone acetate, isothipendyl hydrochloride, benzalkonium chloride, calamine, d-borneol, aqueous ammonia, hydrocortisone, drocortisone acetate, hydrocortisone butyrate, dexamethasone, dexamethasone acetate, prednisolone, prednisolone. Acetate, prednisolone valerate acetate, ufenamate and the like.
  • Local anesthetic ingredients include lidocaine, mepivacaine, bupivacaine, ropivacaine, levopupivacaine, dibucaine, dibucaine hydrochloride, and ethyl aminobenzoate.
  • Keratin softening ingredients include urea, sulfur, and salicylic acid.
  • Bactericidal components include chlorhexidine gluconate, copper chlorophyllin sodium, isopropylmethylphenol, cetylpyridinium chloride hydrate, benzethonium chloride, benzalkonium chloride, resorcinol, acrinol hydrate, chlorhexidine gluconate, povidone iodine, iodine Potassium iodide, mercurochrome, oxideol, cresol, iodoform, thymol and the like.
  • Antibacterial ingredients include undecylenic acid, zinc undecylenate, phenyl-11-iodo-10-undecinoate, exalamide, clotrimazole, econazole nitrate, miconazole nitrate, tioconazole, zinc diethyldithiocarbamate, ciclopirox olamine, siccanin, and tricomycin.
  • the component (A) consists of an anti-inflammatory analgesic component, a local stimulating component, a blood circulation promoting component, an antihistamine component, and a crude drug component from the viewpoint of being an external preparation composition used for exposed and curved parts of the skin. It preferably contains one or more selected from the group, and more preferably contains one or more selected from the group consisting of antiphlogistic analgesic ingredients and local stimulating ingredients.
  • component (A) is glycol salicylate, methyl salicylate, diclofenac sodium, loxoprofen sodium, ketoprofen, felbinac, indomethacin, piroxicam, flurbiprofen, glycyrrhizic acid, glycyrrhetinic acid, l-menthol, dl-camphor, nonyl Acid vanillylamide, mint oil, benzyl nicotinate, sodium polyethylene sulfonate, tocopherol acetate, diphenhydramine, chlorpheniramine maleate, hot pepper, eucalyptus oil, and Phellodendron bark more preferably contain one or more selected from the group consisting of .
  • the solubility parameter (SP value) of component (A) is preferably 15.00 or more, more preferably 18.00 or more, from the viewpoints of having a good appearance of the formed film and from the viewpoint of suppressing the feeling of tightness of the formed film. 00 or more, more preferably 19.00 or more, still more preferably 19.50 or more. From the same viewpoint, it is preferably 35.00 or less, more preferably 27.00 or less, even more preferably 24.00 or less, and even more preferably 22.00 or less.
  • the SP value of component (A) is preferably 15.00 or more and 35.00 or less, more preferably 18.00 or more and 27.00 or less, still more preferably 19.00 or more and 24.00 or less, still more preferably It is 19.50 or more and 22.00 or less.
  • the above SP value can be calculated with a solubility parameter calculation software (Hansen Solubility Parameters in Practice 4th Edition 4.1.03).
  • the SP value is calculated based on Hansen's solubility parameter.
  • the Hansen solubility parameter is obtained by dividing the Hildebrand solubility parameter into three components, a dispersion term ⁇ D, a polar term ⁇ P, and a hydrogen bonding term ⁇ H, and expressing them in a three-dimensional space.
  • the SP value in a mixture of two or more components can be calculated in the following manner.
  • a mixture of two components, component 1 and component 2 is defined as “mixture X”
  • the Hansen solubility parameters of component 1 and component 2 constituting mixture X are [ ⁇ D1, ⁇ P1, ⁇ H1], [ ⁇ D2, ⁇ P2 , ⁇ H2], and the volume ratio of component 1 and component 2 is V1:V2
  • the dispersion term ⁇ Dm, the polar term ⁇ Pm, and the hydrogen bond term ⁇ Hm of the mixture X are represented by the following equations.
  • the specific gravity was calculated as 1.0.
  • ⁇ Dm (V1 ⁇ D1+V2 ⁇ D2)/(V1+V2)
  • ⁇ Pm (V1 ⁇ P1+V2 ⁇ P2)/(V1+V2)
  • ⁇ Hm (V1 ⁇ H1+V2 ⁇ H2)/(V1+V2)
  • the composition of the present invention can suppress crystallization of component (A) in the film and enhance sustained release to the skin even when a highly crystalline component (A) is used. can also improve the storage stability of From the viewpoint of usefulness of this effect, component (A) is preferably one or more crystalline medicinal ingredients selected from the group consisting of glycol salicylate, loxoprofen sodium, felbinac, l-menthol, and nonylic acid vanillylamide. preferable. However, in the composition of the present invention, even if the amorphous component (A) is used, the composition can similarly form a film with high sustained release to the skin.
  • Component (B) water-insoluble polymer>
  • the compositions of the invention contain a water-insoluble polymer as component (B).
  • Component (B) is a film-forming component, which improves the film-forming properties and quick-drying properties of the composition, suppresses the stickiness of the film, and maintains the sustained release of component (A) onto the skin and appearance by the mechanism of action described above. , and the formation of a coating with high durability.
  • component (B) is preferably a film-forming water-insoluble polymer.
  • the definition of "water-insoluble" of component (B) is as described above.
  • the solubility parameter (SP value) of component (B) is preferably 17.00 or more, more preferably 17.00 or more, from the viewpoint of suppressing the feeling of tightness of the formed film and from the viewpoint of improving the sustained release of component (A) to the skin. is 18.00 or more, more preferably 19.00 or more, and even more preferably 20.00 or more.
  • it is preferably 27.00 or less, more preferably 25.00. 00 or less, more preferably 24.00 or less, and even more preferably 23.00 or less.
  • the SP value of component (B) is preferably 17.00 or more and 27.00 or less, more preferably 18.00 or more and 25.00 or less, still more preferably 19.00 or more and 24.00 or less, still more preferably It is 20.00 or more and 23.00 or less.
  • the above SP value can be calculated by a method similar to that described above.
  • the type of component (B) is not particularly limited as long as it is a water-insoluble polymer.
  • (B) is preferably one or more water-insoluble polymers selected from the group consisting of acrylic polymers, cellulose polymers, and vinyl polymers. More preferably, it is one or more water-insoluble polymers selected from the group consisting of acrylic polymers, cellulose polymers, and vinyl polymers, and having an SP value within the above range.
  • acrylic polymers used as component (B) include water-insoluble polymers that include at least structural units derived from monomers having (meth)acrylic groups.
  • (meth)acryl means both acryl and methacryl.
  • Specific examples of the acrylic polymer include (acrylates/diacetoneacrylamide) copolymer, acrylamide/methoxypolyethylene glycol methacrylate copolymer, acrylic acid/octyl acrylate copolymer, acrylic acid ester/acetic acid Vinyl Copolymer, 2-Ethylhexyl Acrylate/Methyl Acrylate/Acrylic Acid/Glycidyl Methacrylate Copolymer, 2-Ethylhexyl Acrylate/Vinyl Acetate/Hydroxyethyl Acrylate/Glycidyl Methacrylate Copolymer, Acrylic Acid 2- Ethylhexyl/diacetone acrylamide/acetoacetoxyethyl meth
  • the (acrylates/diacetoneacrylamide) copolymer is the cosmetic ingredient display name "(alkyl acrylate/diacetoneacrylamide) copolymer AMP", and the acrylamide/methacrylate methoxypolyethylene glycol copolymer is the pharmaceutical product.
  • aminoalkyl methacrylate copolymer E can be used as each.
  • aminoalkyl methacrylate copolymer RS known as a pharmaceutical additive can be used.
  • Examples of the cellulosic polymer used as the component (B) include water-insoluble polymers having a cellulosic skeleton.
  • Examples of the cellulosic polymer include water-insoluble ones selected from methylcellulose, ethylcellulose, hypromellose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose phthalate, hydrophobized (C16-18) hydroxypropylmethylcellulose, and the like. be done.
  • vinyl-based polymers used as component (B) include water-insoluble polymers that are polymers that contain at least a structural unit derived from a monomer having a vinyl group and that do not belong to the above acrylic polymers.
  • examples of the vinyl-based polymer include water-insoluble ones such as polyvinyl alcohol and polyvinyl butyral.
  • Component (B) can be used alone or in combination of two or more.
  • the component (B) is preferably an (acrylates/diacetone acrylamide) copolymer, an acrylamide/methoxypolyethylene glycol methacrylate copolymer, an acrylic acid/octyl acrylic acid ester copolymer, an acrylic acid ester/acetic acid Vinyl Copolymer, 2-Ethylhexyl Acrylate/Methyl Acrylate/Acrylic Acid/Glycidyl Methacrylate Copolymer, 2-Ethylhexyl Acrylate/Vinyl Acetate/Hydroxyethyl Acrylate/Glycidyl Methacrylate Copolymer, Acrylic Acid 2- Ethylhexyl/diacetone acrylamide/acetoacetoxyethyl methacrylate/methyl methacrylate copolymer, 2-ethylhexyl acrylate/vinylpyrrolidon
  • composition of the present invention contains a non-volatile base as component (C) (excluding those corresponding to component (A)).
  • Component (C) has a synergistic effect with component (B) to improve the film-forming properties of the composition, the applicability to the skin, and the quick-drying properties of the composition, thereby improving the sustained release of component (A) to the skin and the composition. It is thought that it also contributes to the improvement of storage stability.
  • the definition of the "non-volatile base" of component (C) is as described above.
  • component (C) examples include lipophilic bases, hydrophilic bases, and amphipathic bases.
  • ) is preferably one or more selected from the group consisting of lipophilic bases and hydrophilic bases, from the viewpoint of enhancing the sustained release of ) to the skin.
  • the component (C) is preferably a compound that does not contain an unsaturated hydrocarbon chain with 16 or more carbon atoms.
  • the content of the non-volatile base containing an unsaturated hydrocarbon chain with 16 or more carbon atoms is preferably 30% by mass from the viewpoint of film formation and the viewpoint of improving the storage stability of the composition. Below, more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 1% by mass or less, and even more preferably 0% by mass.
  • Preferred lipophilic bases include ester oils, non-polar oils and the like.
  • ester oils include non-volatile synthetic ester oils, (i) fatty acid monoesters composed of fatty acids and monohydric alcohols, (ii) fatty acid diesters composed of fatty acids and dihydric alcohols, and (iii) One or more selected from the group consisting of a dicarboxylic acid diester consisting of a dicarboxylic acid and a monohydric alcohol, (iv) a tricarboxylic acid triester consisting of a tricarboxylic acid and a monohydric alcohol, and (v) a glycerol fatty acid triester is more preferred. .
  • Examples of fatty acid monoesters composed of fatty acids and monohydric alcohols include monoesters of saturated fatty acids having 8 to 22 carbon atoms and aliphatic or aromatic ring-containing monohydric alcohols having 1 to 24 carbon atoms.
  • cetyl octanoate cetyl 2-ethylhexanoate, ethyl laurate, hexyl laurate, isopropyl myristate, myristyl myristate, hexadecyl myristate, 2-hexyldecyl myristate, octyldodecyl myristate, isopropyl palmitate , ethylhexyl palmitate, hexadecyl palmitate, 2-hexyldecyl palmitate, 2-heptylundecyl palmitate, butyl stearate, 2-ethylhexyl stearate, isocetyl stearate, isocetyl stearate, isocetyl isostearate, isononyl isononanoate, isotridecyl isononanoate, etc. is mentioned.
  • Fatty acid diesters composed of fatty acids and dihydric alcohols include diesters of saturated fatty acids having 8 to 22 carbon atoms and aliphatic or aromatic dihydric alcohols having 1 to 12 carbon atoms. , ethylene glycol di-2-ethylhexanoate, ethylene glycol dilaurate, ethylene glycol distearate, neopentyl glycol dicaprate, neopentyl glycol diethylhexanoate, di(caprylic/capric) propanediol, propanediol diisostearate, etc. is mentioned.
  • Dicarboxylic acid diesters consisting of a dicarboxylic acid and a monohydric alcohol include an aliphatic or aromatic dicarboxylic acid having 4 to 18 carbon atoms and an aliphatic or aromatic ring-containing monohydric alcohol having 1 to 24 carbon atoms.
  • the tricarboxylic acid triester consisting of tricarboxylic acid and monohydric alcohol includes an aliphatic or aromatic tricarboxylic acid having 5 to 12 carbon atoms and an aliphatic or aromatic ring-containing monovalent having 1 to 24 carbon atoms. Examples thereof include triesters with alcohols, such as triisodecyl trimellitate.
  • glycerin fatty acid triesters include triesters of glycerin and saturated fatty acids having 8 to 22 carbon atoms, such as glycerin tri-2-ethylhexanoate, glycerin trimyristate, tri- 2-Heptylundecanoic acid glycerin, tristearin and the like.
  • Ester oils other than the above (i) to (v) include alkyl benzoate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate, dipentaerythritol fatty acid ester, diisostearyl malate, and di-2-heptyl.
  • Glycerin undecanoate, castor oil fatty acid methyl ester, 2-octyldodecyl N-lauroyl-L-glutamate, 2-hexyldecyl adipate and the like can also be used.
  • the ester oil is one or more selected from the group consisting of (i) fatty acid monoesters consisting of fatty acids and monohydric alcohols, and (iii) dicarboxylic acid diesters consisting of dicarboxylic acids and monohydric alcohols.
  • a fatty acid monoester consisting of a fatty acid and a monohydric alcohol having 1 to 24 carbon atoms
  • a dicarboxylic acid diester consisting of a dicarboxylic acid having 4 to 18 carbon atoms and a monohydric alcohol having 1 to 24 carbon atoms
  • isopropyl myristate, dibutyl adipate, diethyl sebacate, and diisopropyl sebacate are even more preferable.
  • non-polar oils include non-volatile hydrocarbon oils, silicone oils, fluorine oils, and the like.
  • hydrocarbon oil include liquid paraffin and squalane
  • silicone oil examples include dimethylpolysiloxane, dimethylcyclopolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, higher alcohol-modified organopolysiloxane, and the like.
  • Fluorine oils include fluoropolyethers, perfluoroalkyl ether silicones, and the like.
  • the hydrophilic base preferably includes one or more selected from the group consisting of polyols and lower amines.
  • polyols include non-volatile alkylene glycols, polyalkylene glycols, glycerins and the like.
  • alkylene glycols include ethylene glycol, propylene glycol, 1,3-propanediol, 1,3-butylene glycol (1,3-butanediol), and 1,2-pentanediol.
  • polyalkylene glycols examples include , diethylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, polyoxyethylene/polyoxypropylene glycol and the like, and the glycerins include glycerin, diglycerin, triglycerin and the like.
  • Polyethylene glycol, polypropylene glycol, and polyoxyethylene/polyoxypropylene glycol preferably have a weight average molecular weight of 10,000 or less.
  • lower amine refers to an amine having preferably 9 or less carbon atoms, more preferably 2 to 9 carbon atoms.
  • the lower amine is an alkanolamine from the viewpoints of nonvolatility, film-forming property of the composition, improvement of applicability to skin and quick-drying property, and improvement of sustained release of component (A) to skin. is preferred.
  • alkanolamine include triethanolamine, diethanolamine, monoethanolamine, triisopropanolamine, diisopropanolamine, monoisopropanolamine, 2-amino-2-methylpropanol, and the like.
  • Component (C) can be used alone or in combination of two or more.
  • the component (C) is preferably one or more selected from the group consisting of ester oils, non-polar oils, polyols, and alkanolamines, including isopropyl myristate, dibutyl adipate, diethyl sebacate, diisopropyl sebacate, and propylene.
  • composition of the present invention contains a volatile solvent (excluding those corresponding to component (A)) as component (D).
  • Component (D) contributes to improving the applicability, quick-drying property, storage stability, etc. of the composition.
  • the definition of "volatile solvent” for component (D) is as described above.
  • Component (D) includes volatile alcohols, ketones, esters, hydrocarbons, silicones, and the like.
  • the alcohol used as component (D) is preferably a lower alcohol.
  • “Lower alcohol” is preferably a monohydric alcohol having 4 or less carbon atoms, such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, sec-butyl alcohol and tert-butyl alcohol. mentioned.
  • Ketones used as component (D) include acetone, ethyl methyl ketone and methyl isobutyl ketone; esters such as methyl acetate, ethyl acetate and butyl acetate; hydrocarbons such as volatile liquid paraffin; Examples include polydimethylsiloxane and cyclic siloxane.
  • Component (D) is preferably a lower alcohol from the viewpoint of improving the spreadability and quick-drying properties of the composition, the solubility or dispersibility of components (A) to (C), and the storage stability of the composition. More preferably one or more selected from the group consisting of ethanol and isopropyl alcohol.
  • compositions of the present invention contain water as component (E).
  • Component (E) contributes to improvement of storage stability and the like.
  • Component (E) is not particularly limited, and ion-exchanged water, pure water, distilled water, etc. can be used, for example.
  • composition for external use of the present invention may appropriately contain other components usually blended in compositions for external use within a range that does not impair the purpose of the present invention.
  • examples of such components include surfactants, water-soluble polymers, antioxidants, ultraviolet absorbers, vitamins, preservatives, pH adjusters, fragrances, plant extracts other than component (A), moisturizers, and colorings. agents, cooling agents, antiperspirants, skin activators and the like.
  • the content of each component in the topical preparation composition of the present invention is such that the medicinal ingredient can be continuously and gradually released into the skin, and the film-forming property is good, the application property to the skin is high, and the quick-drying property is high. From the viewpoint of obtaining an external preparation composition that is excellent in suppressing the stickiness and tight feeling of the coated film and improving the appearance, durability, etc., the following is preferable.
  • the content of component (A) in the composition is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, and still more preferably 0.005% by mass or more, from the viewpoint of ensuring sufficient effects as a medicinal ingredient. 01% by mass or more, more preferably 0.1% by mass or more, still more preferably 1.0% by mass or more, and from the viewpoint of improving the storage stability of the composition, preferably 30% by mass or less, more preferably It is 20% by mass or less, more preferably 15% by mass or less, even more preferably 10% by mass or less, and even more preferably 5.0% by mass or less.
  • the content of component (A) in the composition is preferably 0.001% by mass or more and 30% by mass or less, more preferably 0.005% by mass or more and 20% by mass or less, and still more preferably 0.01% by mass. 15 mass % or less, more preferably 0.1 mass % or more and 10 mass % or less, further preferably 1.0 mass % or more and 5.0 mass % or less.
  • component (A) contains glycol salicylate
  • the content of glycol salicylate in the composition is preferably 0.1% by mass or more and 30% by mass or less, more preferably 0.5% by mass or more and 20% by mass or less, and further It is preferably 1.0% by mass or more and 15% by mass or less, more preferably 2.0% by mass or more and 12% by mass or less, still more preferably 2.0% by mass or more and 5.0% by mass or less
  • component (A) is When loxoprofen sodium is contained, the content of loxoprofen sodium in the composition is preferably 0.01% by mass or more and 20% by mass or less, more preferably 0.05% by mass or more and 10% by mass or less, and still more preferably 0.1% by mass.
  • component (A) contains felbinac
  • the content of felbinac in the composition is preferably 0.01% by mass or more and 30% by mass or less, more preferably 0.1% by mass or more and 20% by mass or less, still more preferably 0.5% by mass or more and 15% by mass or less, more preferably 1.0% by mass or more and 10% by mass or less, still more preferably 1.5% by mass or more and 5.0% by mass or less
  • component (A) is When l-menthol is contained, the content of l-menthol in the composition is preferably 0.01% by mass or more and 30% by mass or less, more preferably 0.1% by mass or more and 20% by mass or less, still more preferably 0 .5% by mass or more and 10% by mass or less.
  • component (A) contains nonylic acid vanillylamide
  • the content of nonylic acid vanillylamide in the composition is preferably 0.001% by mass or more and 15% by mass or less, more preferably 0.005% by mass or more and 10% by mass.
  • 0.01% by mass or more and 5.0% by mass or less more preferably 0.01% by mass or more and 1.0% by mass or less, and still more preferably 0.01% by mass or more and 0.1% by mass or less be.
  • the content of component (B) in the composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, and still more preferably 0.1% by mass, from the viewpoint of film-forming properties and durability of the film.
  • % by mass or more, more preferably 0.5% by mass or more, still more preferably 1.0% by mass or more, and preferably 30% by mass or less, more preferably 30% by mass or less, from the viewpoint of improving the applicability and quick-drying properties of the composition. is 25% by mass or less, more preferably 20% by mass or less, even more preferably 12% by mass or less, and even more preferably 5.0% by mass or less.
  • the content of component (B) in the composition is preferably 0.01% by mass or more and 30% by mass or less, more preferably 0.05% by mass or more and 25% by mass or less, and still more preferably 0.1% by mass. 20 mass % or less, more preferably 0.5 mass % or more and 12 mass % or less, still more preferably 1.0 mass % or more and 5.0 mass % or less.
  • component (B) contains an (acrylates/diacetone acrylamide) copolymer
  • the content of the copolymer in the composition is more preferably 0.1% by mass or more and 15% by mass or less, and more It is more preferably 0.5% by mass or more and 10% by mass or less, still more preferably 1.5% by mass or more and 5.0% by mass or less
  • the component (B) is an acrylamide/methacrylate methoxypolyethylene glycol copolymer.
  • the content of the copolymer in the composition is more preferably 0.1% by mass or more and 10% by mass or less, and when the component (B) contains ethyl cellulose, ethyl cellulose in the composition
  • the content of is more preferably 0.1% by mass or more and 20% by mass or less
  • component (B) contains hypromellose phthalate the content of hypromellose phthalate in the composition is more preferably 0.1% by mass or more and 20% by mass or less, still more preferably 0.5% by mass or more and 15% by mass or less, and even more preferably 1.0% by mass or more and 10.0% by mass Below, more preferably 1.5% by mass or more and 5.0% by mass or less.
  • component (B) contains polyvinyl butyral the content of polyvinyl butyral in the composition is more preferably 0.1% by mass or more and 20% by mass or less.
  • the content of component (C) in the composition is preferably 0.001% by mass or more, from the viewpoint of improving the sustained release of component (A) to the skin and suppressing the feeling of tightness of the formed film. It is preferably 0.005% by mass or more, more preferably 0.01% by mass or more, still more preferably 0.1% by mass or more, and still more preferably 1.0% by mass or more, from the viewpoint of suppressing stickiness of the formed coating. And from the viewpoint of improving scratch resistance, it is preferably 30% by mass or less, more preferably 20% by mass or less, even more preferably 10% by mass or less, even more preferably 8.0% by mass or less, and even more preferably 5.0% by mass. % by mass or less.
  • the content of component (C) in the composition is preferably 0.001% by mass or more and 30% by mass or less, more preferably 0.005% by mass or more and 20% by mass or less, and even more preferably 0.1% by mass. % or more and 15 mass % or less, more preferably 0.01 mass % or more and 10 mass % or less, still more preferably 0.1 mass % or more and 8.0 mass % or less, still more preferably 1.0 mass % or more5 0% by mass or less.
  • component (C) contains isopropyl myristate
  • the content of isopropyl myristate in the composition is more preferably 0.1% by mass or more and 10% by mass or less, and even more preferably 0.25% by mass or more. 0.5% by mass or less, more preferably 0.5% by mass or more and 5.0% by mass or less
  • the component (C) contains diethyl sebacate the content of diethyl sebacate in the composition is more preferably 0.1% by mass or more and 10% by mass or less, still more preferably 0.25% by mass or more and 7.5% by mass or less, and even more preferably 0.5% by mass or more and 5.0% by mass It is below.
  • component (C) contains diisopropanolamine
  • the content of diisopropanolamine in the composition is more preferably 0.1% by mass or more and 5.0% by mass or less, and even more preferably 0.5% by mass. 4.0% by mass or less, more preferably 1.0% by mass or more and 3.0% by mass or less
  • component (C) contains triethanolamine the content of triethanolamine in the composition is more preferably 0.1% by mass or more and 5.0% by mass or less, still more preferably 1.0% by mass or more and 3.0% by mass or less
  • the content of component (D) in the composition is preferably 10% by mass or more, more preferably 25% by mass or more, and still more preferably 45% by mass, from the viewpoint of improving the coating properties and quick-drying properties of the composition and improving storage stability.
  • % by mass or more more preferably 65% by mass or more, preferably 95% by mass or less, more preferably 90% by mass or less, and even more preferably 80% by mass, from the viewpoint of maintaining the coating properties and film-forming properties of the composition.
  • % by mass or less more preferably 75% by mass or less.
  • the content of component (D) in the composition is preferably 10% by mass or more and 95% by mass or less, more preferably 25% by mass or more and 90% by mass or less, still more preferably 45% by mass or more and 80% by mass or less, Even more preferably, it is 65% by mass or more and 75% by mass or less.
  • the content of ethanol in the composition is more preferably 30% by mass or more and 90% by mass or less, still more preferably 30% by mass or more and 75% by mass or less, still more preferably is 45% by mass or more and 75% by mass or less, and when isopropyl alcohol is contained as component (D), the content of isopropyl alcohol in the composition is more preferably 30% by mass or more and 90% by mass or less, and even more It is preferably 30% by mass or more and 75% by mass or less, and more preferably 45% by mass or more and 75% by mass or less.
  • the content of component (E) in the composition is preferably 0.1% by mass or more, more preferably 0.1% by mass or more, from the viewpoint of improving the coating properties and storage stability of the composition and from the viewpoint of maintaining film-forming properties. It is 0.5% by mass or more, more preferably 5% by mass or more, and even more preferably 13% by mass or more, from the viewpoint of the composition's applicability, from the viewpoint of maintaining the quick-drying property of the composition, and from the viewpoint of improving storage stability.
  • component (E) in the composition is preferably 0.1% by mass or more and 70% by mass or less, more preferably 0.5% by mass or more and 50% by mass or less, and still more preferably 0.5% by mass.
  • component (E) in the composition is 30 mass from the viewpoint of improving the applicability and storage stability of the composition, maintaining film-forming properties, and maintaining good appearance during low-temperature storage. % and 70% by mass or less.
  • the total content of components (A) to (E) in the composition is preferably 50% by mass or more, more preferably 70% by mass or more, and still more preferably 80% by mass or more, Even more preferably, it is 90% by mass or more and 100% by mass or less.
  • the mass ratio [(A)/(B)] of component (A) to component (B) in the composition is preferably 0.01 or more from the viewpoint of improving sustained release of component (A) to the skin. , more preferably 0.02 or more, still more preferably 0.03 or more, still more preferably 0.05 or more, still more preferably 0.10 or more, still more preferably 0.15 or more, and the application of the composition From the viewpoint of improving the properties, storage stability, film-forming properties and durability of the film, it is preferably 50 or less, more preferably 30 or less, even more preferably 20 or less, still more preferably 10 or less, and even more preferably 5.0. Below, more preferably 3.0 or less.
  • the mass ratio [(A)/(B)] in the composition is preferably 0.01 or more and 50 or less, more preferably 0.02 or more and 30 or less, still more preferably 0.03 or more and 20 or less, and still more It is preferably 0.05 or more and 10 or less, still more preferably 0.10 or more and 5.0 or less, and still more preferably 0.15 or more and 3.0 or less.
  • the mass ratio of component (A) to component (C) in the composition [(A)/(C)] is from the viewpoint of improving the sustained release of component (A) to the skin and improving the storage stability of the composition. From the viewpoint of, preferably 0.01 or more, more preferably 0.02 or more, still more preferably 0.03 or more, still more preferably 0.05 or more, still more preferably 0.10 or more, still more preferably 0 .15 or more, preferably 10 or less, more preferably 5.0 or less, and still more preferably 3.0 from the viewpoint of improving the coating properties and storage stability of the composition and the durability of the formed coating. Below, more preferably 2.5 or less, still more preferably 2.0 or less, and still more preferably 1.5 or less.
  • the mass ratio [(A)/(C)] in the composition is preferably 0.01 or more and 10 or less, more preferably 0.02 or more and 5.0 or less, and still more preferably 0.03 or more and 3.0. 0.05 or more and 2.5 or less, still more preferably 0.10 or more and 2.0 or less, and still more preferably 0.15 or more and 1.5 or less.
  • the mass ratio of component (C) to component (B) in the composition [(C)/(B)] is determined from the viewpoint of improving the sustained release of component (A) to the skin and from the viewpoint of improving film-forming properties. , preferably 0.05 or more, more preferably 0.10 or more, still more preferably 0.20 or more, still more preferably 0.50 or more, and preferably 50 or less from the viewpoint of the durability of the formed coating , more preferably 35 or less, still more preferably 20 or less, still more preferably 10 or less, still more preferably 5.0 or less, and even more preferably 3.5 or less.
  • the mass ratio [(C)/(B)] in the composition is preferably 0.05 or more and 50 or less, more preferably 0.10 or more and 35 or less, still more preferably 0.20 or more and 20 or less, and still more It is preferably 0.20 or more and 10 or less, still more preferably 0.20 or more and 5.0 or less, still more preferably 0.50 or more and 5.0 or less, and still more preferably 0.50 or more and 3.5 or less.
  • the mass ratio [(C)/(B)] in the composition is preferably 0.05 or more and 50 or less, more preferably 0.05 or more and 35 or less, still more preferably 0.05 or more and 20 or less, and still more It is preferably 0.05 or more and 10 or less, still more preferably 0.05 or more and 5.0 or less, still more preferably 0.05 or more and 5.0 or less, and still more preferably 0.05 or more and 3.5 or less.
  • the mass ratio of component (E) to component (D) in the composition [(E)/(D)] is preferably 0.005 from the viewpoint of improving the composition's applicability and quick-drying properties, as well as storage stability. above, more preferably 0.05 or more, still more preferably 0.10 or more, even more preferably 0.16 or more, still more preferably 0.20 or more, and from the same viewpoint, preferably 3.0 or less, It is more preferably 2.0 or less, still more preferably 1.0 or less, even more preferably 0.80 or less, and even more preferably 0.40 or less.
  • the mass ratio [(E)/(D)] in the composition is preferably 0.005 or more and 3.0 or less, more preferably 0.05 or more and 2.0 or less, still more preferably 0.10 or more and 1 0.0 or less, more preferably 0.16 or more and 0.80 or less, still more preferably 0.20 or more and 0.40 or less.
  • the mass ratio of component (B) to the total content of component (D) and component (E) in the composition [(B)/ ⁇ (D)+(E) ⁇ ] is, from the viewpoint of improving film formability, preferably 0.001 or more, more preferably 0.01 or more, and still more preferably 0.02 or more; It is more preferably 0.20 or less, even more preferably 0.12 or less, and still more preferably 0.10 or less.
  • the mass ratio [(B)/ ⁇ (D)+(E) ⁇ ] in the composition is preferably 0.001 or more and 1.0 or less, more preferably 0.01 or more and 0.50 or less, and still more preferably is 0.01 or more and 0.20 or less, more preferably 0.01 or more and 0.12 or less, and still more preferably 0.02 or more and 0.10 or less.
  • the mass ratio of component (A) to the total amount of component (B) and component (C) in the composition ensures sufficient efficacy as a medicinal ingredient.
  • it is preferably 0.001 or more, more preferably 0.005 or more, still more preferably 0.01 or more, and even more preferably 0.05 Above, more preferably 0.10 or more, preferably 5.00 from the viewpoint of suppressing crystallization of component (A), the viewpoint of durability of the formed coating, and the viewpoint of improving the storage stability of the composition.
  • the mass ratio [(A)/ ⁇ (B)+(C) ⁇ ] in the composition is preferably 0.001 or more and 5.00 or less, more preferably 0.005 or more and 3.00 or less, and still more preferably is 0.01 or more and 2.50 or less, more preferably 0.05 or more and 2.50 or less, still more preferably 0.10 or more and 2.50 or less, still more preferably 0.10 or more and 1.60 or less, more More preferably 0.10 or more and 1.00 or less, still more preferably 0.10 or more and 0.60 or less.
  • it is preferably 0.001 or more and 2.40 or less, more preferably 0.005 or more and 2.00 or less, still more preferably 0.01 or more and 1.60. Below, more preferably 0.05 or more and 1.00 or less, still more preferably 0.05 or more and 0.60 or less.
  • the viscosity at 25° C. of the composition for external use of the present invention is 1.0 mPa ⁇ s or more, preferably 3.0 mPa ⁇ s, from the viewpoint of improving the applicability to the skin and the uniformity of the formed film. s or more, more preferably 5.0 mPa ⁇ s or more, and still more preferably 10.0 mPa ⁇ s or more. In addition, from the viewpoint of improving the quick-drying property of the composition and improving the appearance of the formed film, it is 10,000 mPa s or less, preferably 7,500 mPa s or less, more preferably 5,000 mPa s or less.
  • the viscosity of the composition for external use at 25° C. is 1.0 mPa ⁇ s or more and 10,000 mPa ⁇ s or less, preferably 3.0 mPa ⁇ s or more and 7,500 mPa ⁇ s or less, more preferably 3.0 mPa ⁇ s or less.
  • the viscosity of the composition for external use at 25°C is a value measured by a vibrating viscometer for compositions of 1,000 mPa s or less, and by a B-type rotational viscometer for compositions exceeding 1,000 mPa s. Specifically, it can be measured by the method described in Examples.
  • the SP value (SP A ) of the component (A) and the component the absolute value of the difference [ ⁇ (SP A ⁇ SP B+C )] from the SP value (SP B+C ) of the mixture of (B) and component (C) is preferably 0.10 or more, more preferably 0.15 or more; More preferably 0.20 or more, still more preferably 0.30 or more, still more preferably 0.50 or more, more preferably 10.00 or less, more preferably 8.00 or less, still more preferably 7.00 or less.
  • [ ⁇ (SP A ⁇ SP B+C )] is preferably 0.10 or more and 10.00 or less, more preferably 0.15 or more and 8.00 or less, still more preferably 0.20 or more and 7.00 or less, and more It is more preferably 0.30 or more and 5.00 or less, more preferably 0.50 or more and 5.00 or less.
  • [ ⁇ (SP A ⁇ SP B+C )] is 0.10 or more, the compatibility between the component (A) and the film is not excessively high, and the spinnability of the formed film can be suppressed. , the sustained release of the component (A) to the skin side is maintained well.
  • the compatibility between the component (A) and the film is not excessively lowered, and the crystallization of the crystalline component (A) can be suppressed, so that the component (A) can be applied to the skin side. Sustained release properties are maintained well.
  • the SP value (SP A ) of component (A) and the SP value (SP B+C ) of the mixture of component (B) and component (C) can be calculated in the same manner as described above.
  • the external preparation composition of the present invention is preferably used as a skin external preparation composition.
  • the dosage form of the composition for external use of the present invention may be a form having a viscosity within the above range and being applicable to the skin.
  • lotion formulations, gel formulations, ointment formulations, cream formulations, or foam formulations comprising the external preparation composition of the present invention; aerosol formulations or pump spray formulations using the external preparation composition of the present invention; mentioned.
  • foam formulations include formulations that are used by filling a pump foamer or the like with the composition for external use of the present invention and discharging it in the form of foam.
  • the compositions of the present invention can also be electrostatically sprayed onto the skin using an electrostatic spray device. Electrostatic spray is described below.
  • An aerosol formulation contains the external preparation composition and a propellant.
  • An aerosol formulation using the composition for external use of the present invention can provide a cooling sensation or the like by spraying the composition onto the skin.
  • the external preparation composition used as the aerosol stock solution and its preferred embodiment are the same as described above. That is, the content and viscosity of components (A) to (E) in the aerosol stock solution are preferably within the above ranges.
  • propellants used in aerosol formulations include liquefied petroleum gas (LPG), which is ethane, propane, normal butane, isobutane, isopentane, and mixtures thereof; ethers such as dimethyl ether; compressed gases such as nitrogen and carbon dioxide; and one or more of these can be used.
  • LPG liquefied petroleum gas
  • the amount ratio of the external preparation composition, which is an aerosol stock solution, and the propellant is not particularly limited as long as the external preparation composition can be sprayed on the skin, but the aerosol performance and component (A) From the viewpoint of stability, the mass ratio of the external preparation composition to the propellant is preferably 1:0.01 to 1:10, more preferably 1:0.05 to 1:7.5.
  • the mass ratio of the composition for external use and LPG is more preferably 1:0.5 to 1:5, and when the propellant is dimethyl ether, the composition for external use and dimethyl ether is more preferably 1:0.1 to 1:5, and when the propellant is carbon dioxide, the mass ratio of the external preparation composition to carbon dioxide is more preferably 1:0.1 ⁇ 1:0.5.
  • Aerosol containers used for aerosol formulations include known pressure-resistant containers made of metal, plastic, etc., and double-structured containers in which an inner bag is housed inside the pressure-resistant container.
  • the inner bag is filled with the external preparation composition as an aerosol undiluted solution, and the space between the pressure-resistant container and the inner bag is filled with the propellant.
  • the method of preparing the aerosol formulation is not particularly limited.
  • it can be prepared by filling the aerosol container with the external preparation composition as an aerosol stock solution, attaching a valve, and then filling the propellant from the valve portion.
  • a pump spray type formulation is a formulation that is used by filling a pump spray container with the external preparation composition of the present invention.
  • the present invention also provides a method of using the composition for external use, comprising the steps of applying the composition for external use to the skin and then drying the composition.
  • the external preparation composition is applied to the skin and then dried to form a film containing the medicinal component (A) on the skin surface. Since the film has excellent moisture resistance and abrasion resistance and has a high sustained release of component (A) to the skin, component (A) can be continuously released to the skin.
  • the step of applying the composition for external use to the skin and then drying it is also referred to as the "coating step”.
  • the method of applying the composition for external use to the skin can be appropriately selected according to the dosage form of the composition for external use, and examples thereof include methods of application by coating, casting, spraying, and the like. Among these, application by coating or spraying is preferable.
  • the component (D) is volatilized by natural drying or the like, and a film containing the components (A) to (C) is formed on the skin surface.
  • the composition for external use when the composition for external use is directly applied to the skin, the composition for external use is applied by hand or using an applicator such as a metal roller, a plastic roller, a sponge-like porous body, or a brush. can be applied.
  • an applicator such as a metal roller, a plastic roller, a sponge-like porous body, or a brush.
  • methods of spraying the composition include methods using an aerosol, a pump spray, or an electrostatic spray device.
  • aerosol and pump spray the external preparation composition can be used as a stock solution to prepare the aforementioned aerosol formulation and pump spray formulation, and the formulation can be used to spray the external preparation composition onto the skin.
  • the electrostatic spray device comprises a container capable of containing the composition for external use, a nozzle for discharging the composition for external use, a power source for applying voltage to the nozzle, and a nozzle from the container to the nozzle.
  • means for delivering the composition for external use is a handheld electrostatic spray device having dimensions that allow it to be held with one hand.
  • the electrostatic spray device those exemplified in International Publication No. 2018/194140 and the like can be used.
  • the application site of the external preparation composition is not particularly limited, but preferably includes the skin surface of the body site, more preferably the skin surface of the hand, arm, foot, leg, or body.
  • the amount of the external preparation composition applied to the skin is not particularly limited, it is preferably 0.5 ⁇ L/cm 2 or more, more preferably 1 ⁇ L/cm 2 from the viewpoint of sufficiently sustained release of component (A) to the skin. Above, more preferably 3 ⁇ L/cm 2 or more. From the viewpoint of the appearance (transparency) of the film to be formed, it is preferably 100 ⁇ L/cm 2 or less, more preferably 50 ⁇ L/cm 2 or less.
  • the present invention also provides a method for producing a film, comprising the step of directly applying or spraying the composition for external use onto the skin.
  • the external preparation composition can be applied by hand or using an applicator such as a metal roller as described above.
  • an applicator such as a metal roller as described above.
  • methods of spraying the composition include methods using the aerosol, pump spray, or electrostatic spray device.
  • the storage part of the handheld electrostatic spray device is filled with the external preparation composition, and the user, i.e., the person who forms the film on the application site of the skin by the electrostatic spray, holds the device by hand, One end of the device, where the nozzle is located, is directed toward the application site for electrostatic spraying. Under this condition, the electrostatic spraying device can be switched on to carry out the electrostatic spraying method. When the device is turned on, an electric field is generated between the nozzle and the skin, and a high positive voltage is applied to the nozzle, making the skin the negative electrode.
  • the topical composition at the tip of the nozzle is polarized by electrostatic induction, and the tip becomes cone-shaped, and droplets of the topical composition are discharged from the tip of the cone. Along the electric field, it is ejected into the air toward the skin.
  • the volatile solvent component (D)
  • the charge density on the surface of the topical composition becomes excessive, and the repulsive force of the coulomb causes repeated miniaturization of the composition into space. and reach the skin.
  • the sprayed composition can be applied to the application site in the form of droplets.
  • the component (D) is volatilized from the droplets while being discharged into the space
  • the component (B) which is the main film-forming component, is solidified, and the fiber is formed while being stretched and deformed by the potential difference. Fibers can also be deposited at the application site. This forms a porous coating of fibrous deposits on the surface of the application site.
  • the present invention further discloses the following embodiments.
  • ⁇ 1> (A) a medicinal ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, and has a viscosity of 1.0 mPa s or more at 25°C, preferably is 3.0 mPa s or more, more preferably 5.0 mPa s or more, still more preferably 10.0 mPa s or more, and 10,000 mPa s or less, preferably 7,500 mPa s or less, more preferably 5 ,000 mPa s or less, more preferably 3,000 mPa s or less, even more preferably 2,000 mPa s or less, still more preferably 1,000 mPa s or less, and even more preferably 700 mPa s or less, for external use agent composition.
  • ⁇ 2> (A) a medicinal ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein The content of component (E) is 0.1% by mass or more and 30% by mass or less, and the mass ratio of component (A) to the total amount of component (B) and component (C) [(A) / ⁇ (B )+(C) ⁇ ] is 0.001 or more and 2.40 or less, and the viscosity at 25° C. is 1.0 mPa ⁇ s or more and 10,000 mPa ⁇ s or less.
  • ⁇ 3> (A) a medicinal ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein The content of component (E) is more than 30% by mass and 70% by mass or less, and the mass ratio of component (A) to the total amount of component (B) and component (C) [(A) / ⁇ (B) +(C) ⁇ ] is 0.001 or more and 2.40 or less, and the viscosity at 25°C is 1.0 mPa ⁇ s or more and 10,000 mPa ⁇ s or less.
  • composition for external use comprises
  • content of component (B) in the external preparation composition is 0.1% by mass or more and 15% by mass or less
  • mass ratio of component (C) to component (B) in the external preparation composition [(C)/(B) ] is 0.05 or more and 3.5 or less
  • the viscosity at 25° C. is 1.0 mPa ⁇ s or more and 10,000 mPa ⁇ s or less.
  • A one or more medicinal ingredients selected from the group consisting of glycol salicylate, diclofenac sodium, loxoprofen sodium, felbinac, indomethacin, piroxicam, flurbiprofen, methyl salicylate, ketoprofen, and nonylic acid vanillylamide;
  • B water-insoluble A topical composition comprising a polymer, (C) a nonvolatile base, (D) a volatile solvent, and (E) water, wherein the content of component (C) in the topical composition is 5.0%. 0% by mass or less, and a viscosity at 25°C of 1.0 mPa ⁇ s or more and 10,000 mPa ⁇ s or less.
  • the viscosity of the external preparation composition at 25° C. is preferably 3.0 mPa ⁇ s or more, more preferably 5.0 mPa ⁇ s or more, still more preferably 10.0 mPa ⁇ s or more, and preferably 7,500 mPa ⁇ s. Below, more preferably 5,000 mPa s or less, still more preferably 3,000 mPa s or less, even more preferably 2,000 mPa s or less, still more preferably 1,000 mPa s or less, still more preferably 700 mPa s s or less, the composition for external use according to any one of ⁇ 2> to ⁇ 5>.
  • the SP value of component (B) is preferably 17.00 or more, more preferably 18.00 or more, still more preferably 19.00 or more, still more preferably 20.00 or more, preferably 27.00 or less, and more
  • the external preparation composition according to any one of ⁇ 1> to ⁇ 6>, which is preferably 25.00 or less, more preferably 24.00 or less, and even more preferably 23.00 or less.
  • the absolute value of the difference between the SP value (SP A ) of component (A ) and the SP value (SP B+C ) of the mixture of component (B) and component (C) [ ⁇ (SP A ⁇ SP B+C )] is preferred.
  • Component (A) is one or more selected from the group consisting of antiphlogistic analgesic components, local stimulating components, blood circulation promoting components, antihistamine components, crude drug components, antipruritic components, local anesthetic components, keratin softening components, bactericidal components, and antibacterial components.
  • Component (A) is glycol salicylate, methyl salicylate, diclofenac sodium, loxoprofen sodium, ketoprofen, felbinac, indomethacin, piroxicam, flurbiprofen, glycyrrhizic acid, glycyrrhetinic acid, l-menthol, dl-camphor, nonylic acid vanillylamide, peppermint oil.
  • benzyl nicotinate sodium polyethylene sulfonate, tocopherol acetate, diphenhydramine, chlorpheniramine maleate, hot pepper, eucalyptus oil, and one or more selected from the group consisting of Phellodendron bark, preferably glycol salicylate, loxoprofen sodium,
  • the external preparation composition according to any one of ⁇ 1> to ⁇ 3> and ⁇ 6> to ⁇ 9>, containing one or more selected from the group consisting of felbinac, l-menthol, and nonylic acid vanillylamide.
  • SP value of component (A) is preferably 15.00 or more, more preferably 18.00 or more, still more preferably 19.00 or more, still more preferably 19.50 or more, preferably 35.00 or less, The external preparation composition according to any one of ⁇ 1> to ⁇ 10>, which is more preferably 27.00 or less, still more preferably 24.00 or less, and even more preferably 22.00 or less.
  • Component (B) is a film-forming water-insoluble polymer, preferably one or more water-insoluble polymers selected from the group consisting of acrylic polymers, cellulosic polymers, and vinyl polymers ⁇ 1> to ⁇ 11> The composition for external use according to any one of Items 11>.
  • the acrylic polymer contains at least a structural unit derived from a monomer having a (meth)acrylic group, and is an (acrylates/diacetoneacrylamide) copolymer, an acrylamide/methoxypolyethylene glycol methacrylate copolymer, acrylic acid/acrylic acid Octyl ester copolymer, acrylic acid ester/vinyl acetate copolymer, 2-ethylhexyl acrylate/methyl acrylate/acrylic acid/glycidyl methacrylate copolymer, 2-ethylhexyl acrylate/vinyl acetate/hydroxyethyl acrylate/ Glycidyl methacrylate copolymer, 2-ethylhexyl acrylate/diacetoneacrylamide/acetoacetoxyethyl methacrylate/methyl methacrylate copolymer, 2-ethylhexyl acrylate/vinylpyrrolidone copolymer,
  • the cellulosic polymer is at least one selected from the group consisting of methylcellulose, ethylcellulose, hypromellose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose phthalate, and hydrophobized (C16-18) hydroxypropylmethylcellulose.
  • Component (B) is (acrylates/diacetoneacrylamide) copolymer, acrylamide-methoxypolyethylene glycol methacrylate copolymer, acrylic acid-octyl acrylate copolymer, acrylate-vinyl acetate copolymer, acrylic acid 2-Ethylhexyl/methyl acrylate/acrylic acid/glycidyl methacrylate copolymer, 2-ethylhexyl acrylate/vinyl acetate/hydroxyethyl acrylate/glycidyl methacrylate copolymer, 2-ethylhexyl acrylate/diacetoneacrylamide/methacryl acetoacetoxyethyl acid/methyl methacrylate copolymer, 2-ethylhexyl acrylate/vinylpyrrolidone copolymer, 2-ethylhexyl acrylate/2-ethylhexyl methacrylate/d
  • Component (C) is one or more selected from the group consisting of lipophilic bases, hydrophilic bases and amphipathic bases, preferably one selected from the group consisting of lipophilic bases and hydrophilic bases
  • the content of the non-volatile base containing an unsaturated hydrocarbon chain having 16 or more carbon atoms in component (C) is preferably 30% by mass or less, more preferably 10% by mass or less, and even more preferably 5% by mass or less,
  • the external preparation composition according to any one of ⁇ 1> to ⁇ 17> which is more preferably 1% by mass or less, and still more preferably 0% by mass.
  • component (C) is one or more selected from the group consisting of ester oils, non-polar oils, polyols, and alkanolamines.
  • the ester oil is (i) a fatty acid monoester consisting of a fatty acid and a monohydric alcohol, (ii) a fatty acid diester consisting of a fatty acid and a dihydric alcohol, (iii) a dicarboxylic acid diester consisting of a dicarboxylic acid and a monohydric alcohol, ( One or more selected from the group consisting of iv) a tricarboxylic acid triester consisting of a tricarboxylic acid and a monohydric alcohol, and (v) a glycerol fatty acid triester, preferably (i) a fatty acid monoester consisting of a fatty acid and a monohydric alcohol and (i
  • the nonpolar oil is one or more selected from the group consisting of hydrocarbon oils, silicone oils, and fluorine oils, preferably liquid paraffin, squalane, dimethylpolysiloxane, dimethylcyclopolysiloxane, methylphenylpolysiloxane, and methylhydrogenpolysiloxane.
  • the external preparation composition according to ⁇ 19> which is at least one selected from the group consisting of siloxane, higher alcohol-modified organopolysiloxane, fluoropolyether, and perfluoroalkylether silicone.
  • the polyol is one or more selected from the group consisting of alkylene glycols, polyalkylene glycols, and glycerins, preferably ethylene glycol, propylene glycol, 1,3-propanediol, 1,3-butylene glycol (1,3 -butanediol), 1,2-pentanediol, diethylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, polyoxyethylene/polyoxypropylene glycol, glycerin, diglycerin, and triglycerin.
  • the external preparation composition according to ⁇ 19>.
  • the alkanolamine preferably has 9 or less carbon atoms, more preferably 2 to 9 carbon atoms, more preferably triethanolamine, diethanolamine, monoethanolamine, triisopropanolamine, diisopropanolamine, monoisopropanolamine, and 2-amino-2-methylpropanol, the external preparation composition according to ⁇ 19>.
  • Component (C) is isopropyl myristate, dibutyl adipate, diethyl sebacate, diisopropyl sebacate, propylene glycol, 1,3-butylene glycol, 1,2-pentanediol, dipropylene glycol, polyethylene glycol, polypropylene glycol, polyoxy One or more selected from the group consisting of ethylene/polyoxypropylene glycol, glycerin, diglycerin, triethanolamine, monoethanolamine, diisopropanolamine, and 2-amino-2-methylpropanol, preferably isopropyl myristate, sebacin
  • the external preparation composition according to any one of ⁇ 1> to ⁇ 23>, which is at least one selected from the group consisting of diethyl acid, triethanolamine, diisopropanolamine, and 2-amino-2-methylpropanol.
  • Component (D) is one or more selected from the group consisting of alcohols, ketones, esters, hydrocarbons, and silicones, preferably lower alcohols, more preferably methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl
  • the content of component (A) in the external preparation composition is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, still more preferably 0.01% by mass or more, and even more preferably 0.01% by mass or more. 1% by mass or more, more preferably 1.0% by mass or more, preferably 30% by mass or less, more preferably 20% by mass or less, even more preferably 15% by mass or less, and even more preferably 10% by mass or less, The external preparation composition according to any one of ⁇ 1> to ⁇ 25>, which is more preferably 5.0% by mass or less.
  • the content of component (B) in the external preparation composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, still more preferably 0.1% by mass or more, and still more preferably 0.5% by mass.
  • % by mass or more more preferably 1.0% by mass or more, preferably 30% by mass or less, more preferably 25% by mass or less, even more preferably 20% by mass or less, even more preferably 12% by mass or less, and still more
  • the external preparation composition according to any one of ⁇ 1> to ⁇ 3> and ⁇ 5> to ⁇ 26>, which is preferably 5.0% by mass or less.
  • the content of component (C) in the external preparation composition is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, still more preferably 0.01% by mass or more, and still more preferably 0.1%.
  • % by mass or more more preferably 1.0% by mass or more, preferably 30% by mass or less, more preferably 20% by mass or less, even more preferably 15% by mass or less, even more preferably 10% by mass or less, and still more
  • the external preparation composition according to any one of ⁇ 1> to ⁇ 4> and ⁇ 6> to ⁇ 27>, which is preferably 8.0% by mass or less, more preferably 5.0% by mass or less.
  • the content of component (D) in the external preparation composition is preferably 10% by mass or more, more preferably 25% by mass or more, even more preferably 45% by mass or more, and even more preferably 65% by mass or more. is 95% by mass or less, more preferably 90% by mass or less, still more preferably 80% by mass or less, and even more preferably 75% by mass or less, ⁇ 1> to ⁇ 28> any one of ⁇ 1> to ⁇ 28>. thing. ⁇ 30>
  • the content of component (E) in the external preparation composition is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, still more preferably 5% by mass or more, and even more preferably 13% by mass or more.
  • the composition for external use according to any one of ⁇ 1> and ⁇ 4> to ⁇ 29>.
  • the mass ratio [(A)/(B)] of component (A) to component (B) in the external preparation composition is preferably 0.01 or more, more preferably 0.02 or more, and still more preferably 0.02 or more.
  • the external preparation composition according to any one of ⁇ 1> to ⁇ 30>, which is more preferably 10 or less, still more preferably 5.0 or less, and still more preferably 3.0 or less.
  • the mass ratio [(A)/(C)] of component (A) to component (C) in the external preparation composition is preferably 0.01 or more, more preferably 0.02 or more, further preferably 0.02 or more.
  • the external preparation composition according to any one of ⁇ 1> to ⁇ 31>, which is 0 or less, more preferably 2.5 or less, still more preferably 2.0 or less, and even more preferably 1.5 or less. . ⁇ 33>
  • the mass ratio [(C)/(B)] of component (C) to component (B) in the external preparation composition is preferably 0.05 or more, more preferably 0.10 or more, further preferably 0.10 or more.
  • the external preparation composition according to any one of ⁇ 1> to ⁇ 3> and ⁇ 5> to ⁇ 32>, wherein the is 3.5 or less.
  • the mass ratio [(E)/(D)] of component (E) to component (D) in the external preparation composition is preferably 0.005 or more, more preferably 0.05 or more, further preferably 0.05 or more.
  • the external preparation composition according to any one of ⁇ 1> to ⁇ 33>, which is 0.80 or less, more preferably 0.40 or less.
  • the mass ratio of component (B) to the total content of component (D) and component (E) in the external preparation composition [(B)/ ⁇ (D)+(E) ⁇ ] is preferably 0.001.
  • the external preparation composition according to any one of ⁇ 1> to ⁇ 34>, more preferably 0.10 or less.
  • the mass ratio of component (A) to the total amount of component (B) and component (C) in the external preparation composition [(A)/ ⁇ (B)+(C) ⁇ ] is preferably 0.001 or more.
  • ⁇ 38> An aerosol formulation or pump spray formulation using the external preparation composition according to any one of ⁇ 1> to ⁇ 36>.
  • ⁇ 40> (A) a medicinal ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, and has a viscosity of 1.0 mPa s or more at 25°C, preferably is 3.0 mPa s or more, more preferably 5.0 mPa s or more, still more preferably 10.0 mPa s or more, and 10,000 mPa s or less, preferably 7,500 mPa s or less, more preferably 5 ,000 mPa s or less, more preferably 3,000 mPa s or less, even more preferably 2,000 mPa s or less, even more preferably 1,000 mPa s or less, and even more preferably 700 mPa s or less.
  • a method of using an external preparation composition comprising the steps of applying the composition to the skin and then drying.
  • ⁇ 41> (A) a medicinal ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein The content of component (E) is 0.1% by mass or more and 30% by mass or less, and the mass ratio of component (A) to the total amount of component (B) and component (C) [(A) / ⁇ (B )+(C) ⁇ ] of 0.001 or more and 2.40 or less and a viscosity of 1.0 mPa ⁇ s or more and 10,000 mPa ⁇ s or less at 25° C. is applied to the skin and then dried.
  • a method of using an external preparation composition comprising the step of applying ⁇ 42> (A) a medicinal ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein The content of component (E) is more than 30% by mass and 70% by mass or less, and the mass ratio of component (A) to the total amount of component (B) and component (C) [(A) / ⁇ (B) +(C) ⁇ ] of 0.001 or more and 2.40 or less and a viscosity of 1.0 mPa ⁇ s or more and 10,000 mPa ⁇ s or less at 25°C is applied to the skin and then dried.
  • a method for using an external preparation composition comprising steps.
  • composition for external use comprises
  • the content of component (B) in the external preparation composition is 0.1% by mass or more and 15% by mass or less, and the mass ratio of component (C) to component (B) in the external preparation composition [(C)/(B) ] is 0.05 or more and 3.5 or less, and the viscosity at 25° C. is 1.0 mPa ⁇ s or more and 10,000 mPa ⁇ s or less, is applied to the skin, and then dried. method of using the agent composition.
  • a topical composition comprising a polymer, (C) a nonvolatile base, (D) a volatile solvent, and (E) water, wherein the content of component (C) in the topical composition is 5.0%.
  • a method for using an external preparation composition comprising the step of applying to the skin an external preparation composition having a viscosity of 0% by mass or less and a viscosity of 1.0 mPa ⁇ s or more and 10,000 mPa ⁇ s or less at 25°C, followed by drying. .
  • the method for spraying the composition for external use is a method using an aerosol, a pump spray, or an electrostatic spray device.
  • ⁇ 47> The method of using the topical composition according to ⁇ 45> or ⁇ 46>, wherein the topical composition is sprayed onto the skin using an electrostatic spray device.
  • a method for producing a coating comprising the step of directly applying or spraying the composition for external use according to any one of ⁇ 1> to ⁇ 36> onto the skin.
  • the method for producing a film according to ⁇ 48>, wherein the method for spraying the composition for external use is a method using an aerosol, a pump spray, or an electrostatic spray device.
  • ⁇ 50> The method for producing a coating according to ⁇ 48> or ⁇ 49>, wherein the external preparation composition is sprayed onto the skin by an electrostatic spray method using an electrostatic spray device.
  • SP value The SP value of the components used in the external preparation composition of each example was calculated based on Hansen's solubility parameters using solubility parameter calculation software (Hansen Solubility Parameters in Practice 4th Edition 4.1.03). In addition, in calculating the SP value, the specific gravity of the component (B) and the component (B'), which are polymer components, was calculated as 1.0.
  • viscosity The viscosity at 25° C. of the external preparation composition of each example was measured using a vibrating viscometer (“VM-10AL” manufactured by Sekonic Co., Ltd.). It was measured using a type rotational viscometer (“TV-10M” manufactured by Toki Sangyo Co., Ltd., rotor: TM3, number of revolutions: 6 rpm).
  • pH The pH of the external preparation composition of each example at 25° C. was measured without dilution using a pH meter (“F-51” manufactured by Horiba, Ltd.).
  • Examples 1 to 42, Comparative Examples 1 to 10 Preparation and evaluation of external preparation composition
  • Component (B) or component (B') described in the table, and other components are mixed with component (C), component (D), and component (E), uniformly dissolved at 30 ° C., and then component ( A) was mixed and dissolved to prepare an external preparation composition.
  • evaluation was performed by the method described above.
  • Tables 1-7 The results are shown in Tables 1-7.
  • the blending amount described in each table is the amount of active ingredient (parts by mass) of each component if there is no description of "% by mass", and the amount of each component that is described as "% by mass”. It is the amount of active ingredients (% by mass).
  • a water-soluble polymer that does not correspond to component (B) is indicated as "component (B')".
  • Hypromellose phthalate "HPMCP HP-55" manufactured by Shin-Etsu Chemical Co., Ltd. *8 Acrylamide-methacrylate methoxypolyethylene glycol copolymer: “RP-77T” manufactured by Kao Corporation * 9 Ethyl cellulose: “Ethocel 100P” manufactured by Nisshin Kasei Co., Ltd. * 10 Polyvinyl butyral: Sekisui Chemical Co., Ltd. "S-lec BM-1" *11 Methyl vinyl ether/maleic anhydride: “Gauntlets AN” manufactured by ISP Japan Co., Ltd.
  • the external preparation composition of the present example has sustained release of the medicinal ingredient, film-forming property, applicability to the skin, quick-drying property, effect of suppressing the stickiness and tight feeling of the formed film, It can be seen that good results are obtained in both appearance and durability. Moreover, the storage stability of the composition is also good. Further, from Table 7, in the external preparation composition of this example, the content of component (E) is more preferably 50% by mass or less, more preferably 30% by mass or less, and even more preferably 25% by mass or less.
  • Formulation Example 1 (Preparation of aerosol formulation) According to the following recipe, component (B) is mixed with component (C), component (D) and component (E) and uniformly dissolved at 30 ° C., then component (A) is mixed and dissolved to form an aerosol stock solution. A composition for external use was prepared. After filling this into an aerosol container (manufactured by Toyo Seikan Co., Ltd.), nitrogen was enclosed so that the mass ratio of the aerosol undiluted solution:nitrogen was 1:0.1 to prepare an aerosol formulation. (Component) (% by mass) (A) Peppermint oil 3.0 (B) polyvinyl alcohol 3.0 (C) diglycerin 3.4 (D) Ethanol 65.0 (E) Purified water balance Total 100.0
  • a medicinal ingredient can be continuously and slowly released to the skin, the film-forming property is good, the applicability to the skin and quick-drying property are high, and stickiness and tightness of the formed film are suppressed. It is possible to provide an external preparation composition excellent in efficacy, appearance and durability of the film, a formulation using the same, a method for using the external preparation composition, and a method for producing a film.

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