WO2023032493A1 - External skin preparation - Google Patents

External skin preparation Download PDF

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Publication number
WO2023032493A1
WO2023032493A1 PCT/JP2022/028041 JP2022028041W WO2023032493A1 WO 2023032493 A1 WO2023032493 A1 WO 2023032493A1 JP 2022028041 W JP2022028041 W JP 2022028041W WO 2023032493 A1 WO2023032493 A1 WO 2023032493A1
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WO
WIPO (PCT)
Prior art keywords
less
composition
mass
skin
component
Prior art date
Application number
PCT/JP2022/028041
Other languages
French (fr)
Japanese (ja)
Inventor
安弘 岡田
利哉 森川
Original Assignee
花王株式会社
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Publication date
Application filed by 花王株式会社 filed Critical 花王株式会社
Priority to CN202280059108.0A priority Critical patent/CN117897150A/en
Publication of WO2023032493A1 publication Critical patent/WO2023032493A1/en

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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
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • 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
    • A61K8/36—Carboxylic acids; Salts or anhydrides 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
    • A61K8/18—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
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • 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
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings

Definitions

  • the present invention relates to an external preparation for skin.
  • contact infection is often the route of infection for bacteria or viruses in people's daily lives.
  • Contact infection is mainly caused by the hands and fingers coming into contact with objects such as bacteria or virus infected persons, doorknobs, handles, tableware, toys, other daily necessities, and interior goods.
  • Patent Document 1 discloses niacinamide or a derivative thereof; a first quaternary ammonium salt containing didecyldimethylammonium chloride; benzethonium chloride, benzalkonium chloride, polydiallyldimethylammonium chloride a second quaternary ammonium salt such as; and a cosmetically acceptable base.
  • An external skin preparation comprising an external skin preparation composition contained in a metered discharge container,
  • the composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid, Among the acids present in the composition, when an acid present in an acid form is defined as the component (A1), the component (A1 ) content is 0.05 mg or more and 80 mg or less.
  • the step of supplying to the site among the acids present in the composition, when the acid existing in the acid form is (A1), it is discharged from the fixed amount discharge container by one discharge operation.
  • the content of the component (A1) in the composition is 0.05 mg or more and 80 mg or less;
  • the bactericidal agent and antibacterial agent used in the technique disclosed in Patent Document 1 are substantially limited in amount to be incorporated into the composition for skin from the viewpoint of safety to the human body. Therefore, the bactericidal or virucidal activity of the skin by the bactericidal agent or antibacterial agent is not sufficient, and further improvement has been desired.
  • An object of the present invention is to provide an external preparation for skin that exhibits excellent bactericidal or virucidal properties and has low skin irritation.
  • the present inventors have solved the above problems by using an external skin preparation containing a composition containing a predetermined organic acid or a salt thereof in a container that can be discharged so as to satisfy predetermined requirements. I found what I can do.
  • component (A1) existing in an acid form refers to one or more acids selected from the group consisting of lactic acid, pyruvic acid and urocanic acid derived from component (A) in the composition. It means the components present as lactic acid, pyruvic acid and urocanic acid.
  • one or more acids selected from the group consisting of lactic acid, pyruvic acid and urocanic acid derived from component (A) are present in the composition as lactate ion, pyruvate ion and urocanate ion.
  • the component that does so is also referred to as "a component that exists in a dissociated form (A2)".
  • bactericidal or virucidal means bactericidal or virucidal of the skin surface to which the external skin composition is applied.
  • bactericidal activity against Serratia can be specifically evaluated by the method described in Examples.
  • the bactericidal and virucidal properties against other bacteria and viruses can be evaluated in consideration of common technical knowledge.
  • the term "exhibiting bactericidal or virucidal properties" means (1) bactericidal/killing activity against bacteria/viruses adhering to the skin surface after the external skin preparation composition is applied to the skin surface.
  • Viral effect (2) Bactericidal and virucidal effect expressed by applying the composition to bacteria and viruses adhering to the skin, (3) Skin conditioning effect that does not mediate bacteria and viruses, (4) ) The effect of protecting the skin from bacteria and viruses and keeping it hygienic, (5) the effect of preventing the spread and contact infection of bacteria and viruses through the skin, and (6) the effect of protecting the skin from infection against bacteria and viruses. It includes the concept of imparting an effect to enhance, and the like.
  • the external skin preparation of the present invention is an external skin preparation comprising an external skin preparation composition (hereinafter also simply referred to as "composition") contained in a metered discharge container, wherein the composition comprises lactic acid, pyruvic acid and When one or more acids selected from the group consisting of urocanic acid or salts thereof (A) are contained, and among the acids present in the composition, those present in an acid form are used as the component (A1) and an external preparation for skin, wherein the content of the component (A1) in the composition discharged from the fixed quantity discharge container by one discharge operation is 0.05 mg or more and 80 mg or less.
  • composition an external skin preparation composition
  • the external preparation for skin of the present invention means a product for external use for skin comprising the above-mentioned external preparation for skin composition and the above-mentioned metered discharge container.
  • the external preparation for skin of the present invention exhibits excellent bactericidal or virucidal properties and has low skin irritation by having the above constitution.
  • the external preparation for skin of the present invention uses component (A) as a bactericidal or virucidal component.
  • Lactic acid, pyruvic acid, and urocanic acid, which are components (A) are originally present on the human skin as supplied from sweat glands, and especially on the fingers, they have bactericidal and virucidal functions against bacteria, viruses, etc.
  • the inventors of the present invention have found that Therefore, it is thought that the composition for external use on the skin containing the component (A) has bactericidal or virucidal properties, is less irritating to the skin, and is highly safe for the human body.
  • compositions containing component (A) also have higher bactericidal or virucidal properties when the pH is lower.
  • lactic acid which is component (A)
  • the present inventors paid attention to the content of the component (A1) present in the acid form among the acids in the external skin preparation composition applied to the skin. Then, the external skin preparation composition containing the component (A) is accommodated in a metered discharge container, and the component (A1) in the composition discharged from the container by one discharge operation is within a predetermined range. , It has been found that it can exhibit excellent bactericidal or virucidal properties and can reduce skin irritation.
  • the external skin preparation of the present invention comprises the external skin preparation composition contained in the quantitative discharge container, and the components ( The content of A1) is 0.05 mg or more and 80 mg or less.
  • the content of A1) in the discharged composition is within the above range, the external preparation for skin exhibits excellent bactericidal or virucidal properties and is less irritating to the skin.
  • the external preparation for skin of the present invention is excellent because "the content of the component (A1) contained in the composition to be discharged" is controlled to be within the above range by one discharging operation. It is possible to easily and stably supply the component (A1) to the skin in an amount that achieves low irritation to the skin while exhibiting bactericidal or virucidal properties.
  • the content of the component (A1) in the composition discharged from the metered discharge container by one discharge operation is preferably 0.1 mg or more, more preferably 0.2 mg or more, from the viewpoint of improving sterilization or virucidal properties. , more preferably 0.4 mg or more, still more preferably 0.5 mg or more, still more preferably 1.0 mg or more, still more preferably 2.0 mg or more, even if the composition is continuously applied to the skin From the viewpoint of easily suppressing skin irritation, it is preferably 60 mg or less, more preferably 50 mg or less, and even more preferably 45 mg or less.
  • the content of component (A1) in the composition discharged from the metered discharge container by one discharge operation is 0.05 mg or more and 80 mg or less, preferably 0.1 mg or more and 60 mg or less, more preferably 0 mg. 2 mg or more and 60 mg or less, more preferably 0.4 mg or more and 50 mg or less, even more preferably 0.5 mg or more and 50 mg or less, even more preferably 1.0 mg or more and 45 mg or less, still more preferably 2.0 mg or more and 45 mg or less .
  • the content of the component (A1) in the composition ejected by one ejection operation can be calculated by the method described in Examples.
  • the content of component (A1) in the composition ejected by one ejection operation is the content of component (A) in the composition used for the external skin preparation of the present invention, the pH of the composition, and the It can be controlled by the viscosity, the type of the metered discharge container, the discharge amount by one discharge operation, or a combination thereof.
  • the amount of the composition discharged from the metered discharge container in one discharge operation is preferable from the viewpoint of improving the bactericidal or virucidal properties and improving the applicability to the skin.
  • the amount of the composition discharged from the fixed quantity discharge container in one discharge operation is preferably 0.05 g or more and 3.0 g or less, more preferably 0.1 g or more and 2.5 g or less, and still more preferably 0 g. .2 g or more and 2.0 g or less.
  • the external preparation for skin of the present invention comprises an external preparation for skin composition containing one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid, contained in a metered discharge container.
  • A one or more acids or salts thereof
  • concentration discharge container refers to a container capable of containing an external skin preparation composition. A container that can dispense a large amount of liquid.
  • Examples of fixed-quantity discharge containers include press-type containers such as stroke-type and squeeze-type containers; electric dispenser-type containers; and the like.
  • a single-use, individually-wrapped container is also included in the metered-discharge container of the present invention.
  • Examples of press-type containers examples of stroke-type press-type containers include pump-type and spray-type containers.
  • the squeeze-type push-type container the squeeze-type push-type container described in Japanese Patent Application Laid-Open No. 2001-151283 can be exemplified.
  • Examples of the electric dispenser type container include a container equipped with a mechanism that automatically discharges a certain amount of the content when a hand is held over a sensor portion.
  • one discharge operation of the fixed quantity discharge container is defined as follows.
  • the fixed quantity dispensing container is a stroke-type pressing container
  • one discharging operation is an operation of pressing the container once with a full stroke.
  • the full stroke here means a state in which a load of 7 kg is applied for 3 seconds by stroke.
  • one discharge operation is an operation of pressing the pressing portion of the container once to squeeze and deform the container.
  • the squeeze deformation as used herein means a state in which a load of 7 kg is applied for 3 seconds by pressing.
  • the pressing portion of the container means, for example, the side peripheral portion of the container, although it varies depending on the shape of the container.
  • the fixed quantity dispensing container is an electric dispenser
  • one dispensing operation is, for example, an operation of holding a hand once over a sensor unit that controls the dispensing of the contents of the container.
  • the volume of the fixed-quantity discharge container assuming multiple discharges is not particularly limited, it is usually in the range of 5 mL or more and 2,000 mL or less from the viewpoint of containing the external skin preparation composition.
  • the external skin preparation composition used in the external skin preparation of the present invention (hereinafter also referred to as the external skin preparation composition of the present invention or the composition of the present invention) is one selected from the group consisting of lactic acid, pyruvic acid and urocanic acid.
  • a composition containing the above acid or salt thereof (A). The composition is housed in the fixed quantity discharge container and discharged from the fixed quantity discharge container for use.
  • Component (A) is one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid and urocanic acid.
  • Component (A) acts as a bactericidal or virucidal component.
  • Examples of salts of lactic acid, pyruvic acid and urocanic acid include alkali metal salts such as potassium salts and sodium salts of lactic acid or pyruvic acid; alkaline earth metal salts such as calcium salts and magnesium salts; amine salts; and ammonium salts. be done.
  • component (A) is preferably lactic acid or a salt thereof, more preferably one or more selected from the group consisting of lactic acid, potassium lactate, sodium lactate, and calcium lactate, and contains lactic acid. is more preferred.
  • component (A) contains lactic acid
  • the content of lactic acid or a salt thereof in the total amount of component (A) is preferably 80% by mass or more, more preferably 90% by mass, from the viewpoint of improving bactericidal or virucidal properties. % or more, and most preferably 100% by mass.
  • the content of component (A) in the composition of the present invention is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, and still more preferably 0.1% by mass or more, from the viewpoint of improving bactericidal or virucidal properties. It is 2% by mass or more, more preferably 0.3% by mass or more, and even more preferably 0.5% by mass or more. In addition, from the viewpoint of suppressing skin irritation, it is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 5.0% by mass or less, even more preferably 4.0% by mass or less, and even more preferably is 3.0% by mass or less, more preferably 2.5% by mass or less, and even more preferably 2.0% by mass or less.
  • the content of component (A) in the composition is preferably 0.05% by mass or more and 15% 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. 10% by mass or less, more preferably 0.2% by mass or more and 5.0% by mass or less, even more preferably 0.3% by mass or more and 4.0% by mass or less, still more preferably 0.5% by mass or more and 3 0 mass % or less, more preferably 0.5 mass % or more and 2.5 mass % or less, and even more preferably 0.5 mass % or more and 2.0 mass % or less.
  • the “content of the component (A)” refers to the acid ("the component present in the acid form (A1)” and “the component present in the dissociated form (A2)”) and the amount obtained by converting the amount of the salt into the dissociated form.
  • the content of component (A1) in the composition of the present invention is preferably 0.02% by mass or more, more preferably 0.04% by mass or more, and still more preferably 0.04% by mass or more, from the viewpoint of improving bactericidal or virucidal properties. 05% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.2% by mass or more, and even more preferably 0.3% by mass or more. In addition, from the viewpoint of suppressing skin irritation, the It is more preferably 2.5% by mass or less, even more preferably 2.0% by mass or less, and even more preferably 1.0% by mass or less.
  • the content of component (A1) in the composition of the present invention is preferably 0.02% by mass or more and 10% by mass or less, more preferably 0.04% by mass or more and 5.0% by mass or less, and still more preferably 0.05% by mass or more and 4.0% by mass or less, more preferably 0.1% by mass or more and 3.0% by mass or less, still more preferably 0.2% by mass or more and 2.5% by mass or less, still more preferably is 0.3% by mass or more and 2.0% by mass or less, more preferably 0.3% by mass or more and 1.0% by mass or less.
  • the content of the component (A1) in the composition of the present invention is such that among the acids derived from the component (A) present in the composition of the present invention, those present in the acid form are the components (A1), dissociated When the component (A2) is present in the form, it can be calculated from the following formula.
  • Content (% by mass) of component (A1) in the composition content (% by mass) of component (A) in the composition x molar ratio in the composition [(A1) / ⁇ (A1) + (A2 ) ⁇ ]
  • the "molar ratio [(A1) / ⁇ (A1) + (A2) ⁇ ] in the composition” refers to the total of component (A1) and component (A2) present in the composition (A1 ), which can be specifically calculated by the method described in Examples in the present invention.
  • the molar ratio [(A1)/ ⁇ (A1)+(A2) ⁇ ] in the composition is preferably 0.2 or more, more preferably 0.3 or more, and still more preferably from the viewpoint of improving bactericidal or virucidal properties.
  • the composition is 0.4 or more. From the viewpoint of suppressing skin irritation, it is preferably 0.6 or less, more preferably 0.55 or less, and even more preferably 0.5 or less. Then, among the acids derived from the component (A) present in the composition, when the acid present in the acid form is the component (A1) and the acid present in the dissociated form is the component (A2), the composition
  • the molar ratio [(A1) / ⁇ (A1) + (A2) ⁇ ] is preferably 0.2 to 0.6, more preferably 0.3 to 0.55, and still more preferably 0.4 0.5 or less.
  • the skin external preparation composition can further contain a nonionic thickener as component (B) from the viewpoint of improving the feeling of use.
  • a nonionic thickener as component (B) from the viewpoint of improving the feeling of use.
  • the term "good feeling in use” means that the composition for external use for skin is applied to the skin, dried, and then moistened with water with little squeaky feeling and good feel.
  • the component (B) used in the composition of the present invention is a water-soluble nonion from the viewpoint of improving the feeling of use, improving or maintaining the bactericidal or virucidal properties, and improving the solubility in the composition. It is preferably a viscous thickener.
  • the component (B) include cellulose ethers such as hydroxybutylmethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and hydroxyethylcellulose; propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropyl guar gum, locust bean gum, and amylose. , hydroxyethyl amylose, starch or derivatives thereof, and the like, and one or more of these can be used.
  • the component (B) is preferably one or more selected from the group consisting of cellulose ethers and polyvinyl alcohol from the viewpoint of maintaining the bactericidal or virucidal properties and improving the feeling of use of the composition.
  • hydroxybutylmethylcellulose more preferably one or more selected from the group consisting of hydroxybutylmethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, and polyvinyl alcohol, more preferably one or more selected from the group consisting of hydroxyethylcellulose and polyvinyl alcohol , and more preferably hydroxyethyl cellulose.
  • the polymerization degree of the polyvinyl alcohol used as the component (B) is preferably 500 or more, more preferably 700 or more, still more preferably 1,000 or more, and still more preferably 1,000 or more, from the viewpoint of improving the feeling of use of the composition. It is 500 or more, more preferably 2,000 or more, preferably 8,000 or less, more preferably 6,000 or less, and still more preferably 5,000 or less from the viewpoint of the ejection property of the composition.
  • the degree of polymerization of polyvinyl alcohol is preferably 500 or more and 8,000 or less, more preferably 700 or more and 8,000 or less, still more preferably 1,000 or more and 6,000 or less, and even more preferably 1,500 or more and 6,000 or less.
  • the saponification degree of polyvinyl alcohol is not particularly limited, it is preferably 80 mol% or more, more preferably 85 mol% or more, still more preferably 90 mol% or more, still more preferably from the viewpoint of improving the feeling of use of the composition. It is 95 mol % or more and 100 mol % or less.
  • a commercially available nonionic thickener can also be used as component (B).
  • hydroxyethyl cellulose examples include "Natrosol HEC 250HHX” manufactured by Ashland and "HEC Daicel 850SE” manufactured by Daicel. be done.
  • the content of component (B) in the composition in the present invention is preferably 0.01% by mass or more, more preferably 0.02% by mass, from the viewpoint of improving the feeling of use of the composition. % or more, more preferably 0.05% by mass or more, still more preferably 0.1% by mass or more, and even more preferably 0.2% by mass or more, and the ejection property of the composition in the present invention, and the sterilization or From the viewpoint of improving or maintaining virucidal properties, the content is preferably 20% by mass or less, more preferably 15% by mass or less, even more preferably 10% by mass or less, even more preferably 5% by mass or less, and even more preferably 3% by mass.
  • component (B) in the composition of the present invention is preferably 0.01% by mass or more and 20% by mass or less, more preferably 0.02% by mass or more and 15% by mass or less, and still more preferably 0.02% by mass or more and 15% by mass or less.
  • the external skin preparation composition of the present invention preferably further contains water.
  • the content of water in the composition is preferably 40% by mass or more, more preferably 70% by mass or more, and still more preferably 80% by mass or more, from the viewpoint of dissolving the component (A) and improving the dischargeability. , more preferably 85% by mass or more, still more preferably 90% by mass or more, still more preferably 95% by mass or more, and preferably 99.95% by mass or less.
  • the total content of component (A) and water in the external skin preparation composition of the present invention is preferably 70.05% by mass or more, more preferably 75% by mass or more, still more preferably 80% by mass or more, even more preferably 85% by mass or more, still more preferably 90% by mass or more, and even more preferably 95% by mass or more There is, and it is 100 mass % or less.
  • the external composition for skin of the present invention has a polarity close to that of the skin surface, is easily spreadable on the skin, and exhibits a bactericidal or virucidal component evenly on the intended application surface, and further contains a polyol. can contain.
  • the polyol those satisfying a logPow value of -2.0 or more, which is the octanol/water partition coefficient, can be preferably used.
  • a higher logPow value indicates higher hydrophobicity, and by including a predetermined amount of such a polyol in the composition, it can be expected that the composition will be made hydrophobic and will be more compatible with the skin than pure water.
  • the logPow values of polyols are calculated according to Renxiao Wang et al. , J. Chem. Inf. Model. 2007, Vol. 47, pp. 2140 can be used to determine the calculated value.
  • polyols include propylene glycol (1,2-propanediol), 1,3-propanediol, dipropylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,3-butanediol, 1,2-pentanediol, 1,5-pentanediol, 1,2-hexanediol, 2,5-hexanediol, 1,6-hexanediol, 1,2-heptanediol, 1 ,7-heptanediol, 1,2-octanediol, 1,8-octanediol, 1,2-nonanediol, 1,9-nonanediol, 1,2-decanediol, 1,10-decanediol, 1, Linear diols such as 2-dodecanediol, 1,12-dol,
  • the content of the polyol in the topical skin preparation composition is such that it can be easily spread over the skin and the bactericidal or virucidal component can be exhibited evenly on the intended application surface. Therefore, it is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.5% by mass or more, still more preferably 1.0% by mass or more, and still more preferably 1.0% by mass or more. 5% by mass or more, more preferably 2.0% by mass or more, and from the viewpoint of reducing stickiness during application, preferably 50% by mass or less, more preferably 30% by mass or less, and further preferably 20% by mass. % or less.
  • the polyol content in the external skin preparation composition is preferably 0.05% by mass or more and 50% by mass or less, more preferably 0.1% by mass or more and 50% by mass or less, and still more preferably 0.5% by mass. % by mass or more and 30% by mass or less, more preferably 1.0% by mass or more and 30% by mass or less, even more preferably 1.5% by mass or more and 20% by mass or less, still more preferably 2.0% by mass or more and 20% by mass % or less.
  • the skin external preparation composition of the present invention preferably contains a pH adjuster from the viewpoint of adjusting the pH to a suitable range.
  • the pH adjuster may be any component as long as it can adjust the pH of the composition to a desired range, and examples thereof include acid components, alkali components, buffer components, and the like. Among these, it is preferable to use at least an alkaline component as a pH adjuster from the viewpoint of adjusting the pH of the composition containing component (A) at 25° C. to the range described below (preferably 3.5 or higher).
  • the alkali component either an organic alkali agent or an inorganic alkali agent can be used, but the inorganic alkali agent is preferable from the viewpoints of solubility in water, availability and economy.
  • inorganic alkaline agents include metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide, metal carbonates such as sodium carbonate and sodium hydrogen carbonate, and the like. can be used. Among these, from the viewpoint of availability and economy, it is preferably one or more selected from the group consisting of alkali metal hydroxides and alkaline earth metal hydroxides, more preferably alkali metal metals It is a hydroxide, more preferably one or more selected from the group consisting of sodium hydroxide and potassium hydroxide, and still more preferably sodium hydroxide.
  • the content of the pH adjuster in the composition may be an amount that can adjust the pH of the composition to a desired range.
  • the external skin preparation composition contains an alkali metal hydroxide and an alkali One or more selected from the group consisting of hydroxides of earth metals is preferably used. Alkali metal hydroxides and alkaline earth metal hydroxides are as described above.
  • the metal ion concentration in the external skin preparation composition is preferably 0.002 mol/L or more, More preferably 0.005 mol/L or more, still more preferably 0.01 mol/L or more, still more preferably 0.02 mol/L or more.
  • the metal ion concentration in the skin external preparation composition is preferably 0.80 mol/L or less, more preferably 0.50 mol/L or less, still more preferably 0.30 mol/L, from the viewpoint of maintaining the mineral balance of the skin. L or less, more preferably 0.20 mol/L or less.
  • the metal ion concentration in the external skin composition is preferably 0.002 mol/L or more and 0.80 mol/L or less, more preferably 0.002 mol/L or more and 0.50 mol/L or less, and still more preferably 0.002 mol/L or more and 0.50 mol/L or less.
  • 005 mol/L or more and 0.50 mol/L or less more preferably 0.01 mol/L or more and 0.30 mol/L or less, still more preferably 0.02 mol/L or more and 0.20 mol/L or less.
  • the term "metal ion concentration in an external skin preparation composition” means the concentration of all metal ions present in the composition. In the composition used in the present invention, it is mainly the total concentration of the metal ions derived from the predetermined organic acid salt contained in the component (A) and the metal ions derived from the pH adjuster. In general, the presence of metal ions in the composition tends to inhibit the bactericidal efficacy of bactericidal agents such as benzalkonium chloride. However, in the skin external preparation composition used in the present invention, the bactericidal or virucidal properties of the component (A) are not inhibited by metal ions, and thus excellent bactericidal or virucidal properties can be exhibited. The metal ion concentration in the composition can be measured by an ion selective electrode method.
  • the external skin preparation composition of the present invention may optionally contain other ingredients such as surfactants, ultraviolet absorbers, antioxidants, preservatives, antiperspirants, fragrances, moisturizers, and feel agents. Modulators, anti-inflammatory agents and the like can also be included.
  • the external skin preparation composition of the present invention does not contain a monoalcohol having 4 or less carbon atoms such as ethanol and isopropanol. It is capable of expressing virucidal properties. Furthermore, from the viewpoint of suppressing skin irritation, the content of monoalcohol having 4 or less carbon atoms in the composition is preferably 60% by mass or less, more preferably 50% by mass or less, and still more preferably 40% by mass or less.
  • Component (C) Organic acid or salt thereof other than component (A)
  • the external skin preparation composition contains an organic acid other than component (A) or a salt thereof (hereinafter also referred to as "component (C)").
  • Bactericidal or virucidal properties can be expressed without blending.
  • the content of the organic acid or its salt (C) other than the component (A) in the composition is preferably 15% by mass or less, more preferably 10% by mass or less.
  • component (C) is an organic acid salt
  • content of the component (C) refers to the amount in terms of the organic acid.
  • the mass ratio [(C)/(A)] of an organic acid other than component (A) or a salt thereof (C) to component (A) in the external skin preparation composition has bactericidal or virucidal properties. From the viewpoint of maintenance and the viewpoint of suppressing skin irritation, it is preferably less than 1, more preferably 0.8 or less, still more preferably 0.6 or less, even more preferably 0.5 or less, and still more preferably 0.3 or less, more preferably 0.2 or less, still more preferably 0.1 or less, still more preferably 0.05 or less, still more preferably 0.01 or less, and even more preferably substantially zero be.
  • Examples of organic acids other than component (A) or salts thereof corresponding to component (C) include carboxylic acid compounds other than component (A), sulfonic acid compounds, and salts thereof.
  • Examples of the carboxylic acid compounds or salts thereof include aliphatic monocarboxylic acids having 4 or less carbon atoms such as acetic acid, propionic acid and butanoic acid; aromatic monocarboxylic acids such as benzoic acid; malonic acid, succinic acid, Aliphatic dicarboxylic acids such as glutaric acid, adipic acid, maleic acid, fumaric acid; Aromatic dicarboxylic acids such as phthalic acid and isophthalic acid; Polycarboxylic acids such as polyglutamic acid; Malic acid, glycolic acid, hydroxyacrylic acid, glyceric acid hydroxycarboxylic acids such as , tartaric acid and citric acid; acidic amino acids such as glutamic acid and aspartic acid; pyrrolidonecarboxylic acid;
  • Examples of the sulfonic acid compounds or salts thereof include aliphatic sulfonic acids such as methanesulfonic acid and ethanesulfonic acid; aromatic sulfonic acids such as p-toluenesulfonic acid and naphthalenesulfonic acid; and salts thereof.
  • Examples of the salt of the organic acid include alkali metal salts such as potassium salts and sodium salts; alkaline earth metal salts such as calcium salts and magnesium salts; amine salts; and ammonium salts.
  • the external skin preparation composition includes quaternary ammonium salts such as benzalkonium chloride and benzethonium chloride; alkyldiaminoethylglycine chlorides and alkylpolyamino chlorides; amphoteric surfactants such as ethylglycine; biguanides such as chlorhexidine gluconic acid; sodium hypochlorite; aldehydes such as glutaral, phthalal and formalin; It exhibits bactericidal or virucidal properties without adding any agents.
  • quaternary ammonium salts such as benzalkonium chloride and benzethonium chloride
  • alkyldiaminoethylglycine chlorides and alkylpolyamino chlorides amphoteric surfactants such as ethylglycine
  • biguanides such as chlorhexidine gluconic acid
  • sodium hypochlorite aldehydes
  • the content of the disinfectant in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, and even more preferably is 3% by mass or less, more preferably 1% by mass or less, even more preferably 0.07% by mass or less, still more preferably 0.05% by mass or less, and even more preferably 0.03 % by mass or less, more preferably less than 0.01% by mass, and most preferably substantially 0% by mass.
  • the content of the fungicide in the composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, from the viewpoint of improving bactericidal or virucidal properties.
  • the mass ratio of the disinfectant to component (A) (sterilant/component (A)) is preferably 0.5 or less, more preferably 0.2 or less, and still more preferably, from the viewpoint of suppressing skin irritation. is 0.1 or less, more preferably 0.05 or less, still more preferably 0.03 or less, still more preferably 0.01 or less, and is most preferably substantially 0.
  • the mass ratio of the fungicide to component (A) is preferably 0.01 or more, and more Preferably it is 0.05 or more.
  • the above-mentioned agent that is a bactericide and also acts as a surfactant is defined as a bactericide.
  • the viscosity of the external preparation composition for skin at 25° C. is preferably 1.0 mPa ⁇ s or more from the viewpoint of uniforming the discharge amount per discharge operation of the metered discharge container and from the viewpoint of improving the applicability to the skin.
  • the viscosity of the external skin preparation composition the more difficult it is to control the amount supplied to the skin. It is advantageous in that it can be supplied.
  • the metered discharge container containing the composition is a stroke-type and pump-type pressing container, the viscosity of the composition at 25° C. is further increased from the viewpoint of enhancing dischargeability and spreadability during application.
  • the viscosity may be 5.0 mPa ⁇ s or more, further 100 mPa ⁇ s or more.
  • the viscosity may be 5.0 mPa ⁇ s or more, further 10.0 mPa ⁇ s or more.
  • the viscosity of the composition at 25° C. is more preferably 25,000 mPa ⁇ s or less, still more preferably 25,000 mPa ⁇ s or less, from the viewpoint of metered discharge performance. is 10,000 mPa s or less, more preferably 8,000 mPa s or less, even more preferably 6,500 mPa s or less, and even more preferably 2,000 mPa s or less. It is preferably 100 mPa ⁇ s or more, and more preferably 500 mPa ⁇ s or more.
  • the fixed-quantity discharge container containing the composition is an electric dispenser container, the viscosity of the composition at 25° C.
  • the viscosity may be 5.0 mPa ⁇ s or more, further 10.0 mPa ⁇ s or more. Specifically, the viscosity of the composition at 25° C. can be measured by the method described in Examples.
  • the skin external preparation composition preferably has a pH at 25°C of 3.5 or more, from the viewpoint of adjusting the content ratio of the component (A1) in the composition of the present invention and from the viewpoint of suppressing skin irritation. More preferably, it is 3.7 or more. From the viewpoint of improving bactericidal or virucidal properties, it is preferably 5.0 or less, more preferably 4.5 or less.
  • the pH of the external skin preparation composition at 25°C is preferably 3.5 or more and 5.0 or less, more preferably 3.5 or more and 4.5 or less, and still more preferably 3.7 or more and 4.5 or less. .
  • the pH of the composition at 25°C can be measured by the method described in Examples.
  • the external skin preparation composition used in the present invention may have fluidity at 25°C.
  • the form is not particularly limited, and may be, for example, liquid, gel, cream, or foam. It is preferably in a liquid form, from the viewpoint of being easy to spread on the skin and exhibiting the bactericidal or virucidal component evenly on the intended application surface.
  • it is preferably gel-like, cream-like, or foam-like.
  • the composition may be in the form of an emulsion composition, and the emulsion composition may be either an oil-in-water emulsion composition or a water-in-oil emulsion composition.
  • An oil-in-water emulsified composition is preferred from the viewpoint of easy application to the skin and the ability to exhibit the bactericidal or virucidal component evenly on the intended application surface.
  • it is preferably a water-in-oil emulsion composition.
  • the external preparation for skin of the present invention is more preferably in the following (I) or (II) mode.
  • An external skin preparation comprising an external skin preparation composition contained in a metered discharge container,
  • the composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid, Among the acids present in the composition, when an acid present in an acid form is defined as the component (A1), the component (A1 ) content of 0.05 mg or more and 80 mg or less,
  • the component (A) is lactic acid or a salt thereof,
  • the mass ratio [(C)/(A)] of the organic acid other than the component (A) or a salt thereof (C) to the component (A) in the composition is less than 1;
  • An external preparation for skin, wherein has a pH of 3.5 or more and 5.0 or less at 25°C.
  • An external skin preparation comprising an external skin preparation composition contained in a metered discharge container,
  • the composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid, Among the acids present in the composition, when an acid present in an acid form is defined as the component (A1), the component (A1 ) content of 0.05 mg or more and 80 mg or less,
  • the composition further contains a nonionic thickener (B), An external preparation for skin, wherein the composition has a viscosity of 100 mPa ⁇ s or more and 10,000 mPa ⁇ s or less at 25°C.
  • the external preparation for skin according to the aspect (I) exhibits a remarkable effect of improving bactericidal or virucidal properties by having the above constitution.
  • the mass ratio of the organic acid or its salt (C) other than the component (A) to the component (A) in the external skin preparation composition used for the external skin preparation of the aspect (I) [(C)/(A )] is less than 1, preferably 0.8 or less, more preferably 0.6 or less, even more preferably 0.5 or less, even more preferably 0.3 or less, even more preferably 0.2 or less, It is even more preferably 0.1 or less, still more preferably 0.05 or less, still more preferably 0.01 or less, and even more preferably substantially zero.
  • the external skin preparation composition used in the external skin preparation of the aspect (I) is 3.5 or more and 5.0 or less, preferably 3.5 or more and 4.5 or less, more preferably 3. .7 or more and 4.5 or less.
  • Other requirements and preferred ranges are the same as above.
  • the external preparation for skin according to the aspect (II) can achieve both bactericidal or virucidal properties and a better feel during use by having the above constitution.
  • the viscosity at 25° C. of the external skin preparation composition used in the external skin preparation of the aspect (II) is 100 mPa ⁇ s or more and 10,000 mPa from the viewpoint of maintaining the bactericidal or virucidal properties and improving the feeling of use.
  • s or less preferably 100 mPa s or more and 5,000 mPa s or less, more preferably 100 mPa s or more and 8,000 mPa s or less, still more preferably 100 mPa s or more and 2,000 mPa s or less more preferably 100 mPa ⁇ s or more and 1,000 mPa ⁇ s or less, still more preferably 100 mPa ⁇ s or more and 800 mPa ⁇ s or less, still more preferably 100 mPa ⁇ s or more and 700 mPa ⁇ s or less.
  • Other requirements and preferred ranges are the same as above.
  • the external preparation for skin of the present invention exhibits bactericidal or virucidal properties on the skin surface by leaving component (A), which is a bactericidal or virucidal component, contained in the discharged composition on the skin surface.
  • the external skin preparation of the present invention is preferably a leave-on skin preparation. That is, when the external skin preparation of the present invention is used, the composition discharged from a metered discharge container is applied to the skin by coating or the like, and then the composition is not removed by washing with water or the like, but left on the skin surface before use. .
  • the external skin preparation of the present invention is more preferably a leave-on skin preparation for fingers.
  • Bacteria or viruses for which the external preparation for skin of the present invention exhibits bactericidal or virucidal properties are not particularly limited as long as they are inactivated or killed by contact with acid. It is thought that the microorganisms described in the guidelines for infectious disease control in Japan can be applied.
  • the bacteria include Gram-positive bacteria such as Bacillus anthracis, Mycobacterium tuberculosis, Streptococcus hemolyticus, Staphylococcus aureus, and Streptococcus pneumoniae, or Gram-negative bacteria such as Tularemia, Yersinia pestis, Brucella, and Bacillus mallei.
  • Viruses include envelope viruses such as arenavirus, ebola virus, smallpox virus, nairovirus, marburg virus, coronavirus, monkeypox virus, beta coronavirus, influenza virus, respiratory syncytial virus, herpes virus, mumps virus, and varicella virus. ⁇ Herpes zoster virus, rubella virus, measles virus, etc., and non-enveloped viruses such as enterovirus, adenovirus, coxsackievirus, norovirus, rotavirus, etc.
  • bactericidal and virucidal properties were evaluated using Serratia as an example, but the target bacteria or viruses of the present invention are not limited thereto.
  • the present invention also provides a method for supplying one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid to an application site on the skin surface, comprising the following steps (I) and A method having (II) in order (hereinafter also simply referred to as "the method of the present invention") is provided.
  • Step (II) The composition containing the component (A) is discharged from a metered discharge container containing the composition by one discharge operation, and the application is performed.
  • step of supplying to the site when the acid existing in the acid form is (A1), it is discharged from the fixed amount discharge container by one discharge operation.
  • a step in which the content of component (A1) in the composition is 0.05 mg or more and 80 mg or less
  • the component (A), the composition containing the component (A), the metered discharge container, and preferred embodiments thereof are the same as described above.
  • step (I) water, soap, body soap, hand soap, etc. are used in advance to wash the application site on the skin surface. After washing, the skin is in a state where naturally occurring components such as lactic acid are washed away, and the defense against external bacteria and viruses is reduced. Therefore, step (II) is performed after step (I). It is preferred to apply the composition and carry out the method of the invention in.
  • step (I) After washing in step (I), the application site on the skin surface can be dried by air drying or the like before step (II) can be performed.
  • step (II) the composition containing component (A) is discharged onto the application site on the skin surface that has been washed in step (I).
  • the content of the component (A1) in the composition discharged from the metered discharge container by one discharge operation is 0.05 mg or more, preferably 0.1 mg or more, from the viewpoint of improving sterilization or virucidal properties.
  • the content of component (A1) in the composition discharged from the metered discharge container by one discharge operation is 0.05 mg or more and 80 mg or less, preferably 0.1 mg or more and 60 mg or less, more preferably 0 mg.
  • component (A1) in the composition ejected by one ejection operation can be obtained by the same method as described above.
  • the composition After supplying the composition to the skin in step (II), it is preferable to leave the composition on the skin surface without removing it by washing with water or the like. This is because the composition can be used as a leave-on preparation to leave the component (A), which is a bactericidal or virucidal component, on the skin surface, thereby imparting bactericidal or virucidal properties to the skin surface.
  • component (A) which is a bactericidal or virucidal component
  • An external skin preparation comprising an external skin preparation composition contained in a fixed-quantity discharge container,
  • the composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid, Among the acids present in the composition, when an acid present in an acid form is used as the component (A1), the component (A1) in the composition discharged from the metered discharge container by one discharge operation content of 0.05 mg or more and 80 mg or less.
  • the content of the component (A1) in the composition discharged from the fixed quantity discharge container by one discharge operation is preferably 0.1 mg or more and 60 mg or less, more preferably 0.2 mg or more and 60 mg or less, still more preferably 0.4 mg or more and 50 mg or less, still more preferably 0.5 mg or more and 50 mg or less, still more preferably 1.0 mg or more and 45 mg or less, still more preferably 2.0 mg or more and 45 mg or less, for external use on the skin according to ⁇ 1> agent.
  • the amount of the composition discharged from the fixed quantity discharge container in one discharge operation is preferably 0.05 g or more and 3.0 g or less, more preferably 0.1 g or more and 2.5 g or less, and still more preferably 0.2 g.
  • the external preparation for skin according to ⁇ 1> or ⁇ 2> which is 2.0 g or less.
  • ⁇ 4> Any of ⁇ 1> to ⁇ 3>, wherein the component (A) contains lactic acid or a salt thereof, preferably one or more selected from the group consisting of lactic acid, potassium lactate, sodium lactate, and calcium lactate, more preferably lactic acid. 1.
  • the skin external preparation according to 1. ⁇ 5> The component (A) contains lactic acid, and the content of lactic acid or a salt thereof in the total amount of component (A) is preferably 80% by mass or more, more preferably 90% by mass or more, and most preferably 100% by mass. %, the skin external preparation according to any one of ⁇ 1> to ⁇ 4>.
  • the content of component (A) in the composition is preferably 0.05% by mass or more and 15% 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 or more. 10 mass % or less, more preferably 0.2 mass % or more and 5.0 mass % or less, even more preferably 0.3 mass % or more and 4.0 mass % or less, still more preferably 0.5 mass % or more3.
  • the skin external preparation according to 1.
  • the content of component (A1) in the composition is preferably 0.02% by mass or more and 10% by mass or less, more preferably 0.04% by mass or more and 5.0% by mass or less, and still more preferably 0.05% by mass. % or more and 4.0 mass % or less, more preferably 0.1 mass % or more and 3.0 mass % or less, still more preferably 0.2 mass % or more and 2.5 mass % or less, still more preferably 0.3 mass %
  • the external preparation for skin according to any one of ⁇ 1> to ⁇ 6>, which is 0.3% to 1.0% by mass, more preferably 0.3% to 1.0% by mass.
  • the composition when the component (A1) exists in an acid form and the component (A2) exists in a dissociated form, the composition is preferably 0.2 or more and 0.6 or less, more preferably 0.3 or more and 0.55 or less, still more preferably 0.4
  • the composition further contains a nonionic thickener as component (B).
  • the component (B) is a water-soluble nonionic thickener, preferably cellulose ethers, propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropyl guar gum, locust bean gum, amylose, hydroxyethyl amylose, starch or derivatives thereof.
  • the degree of polymerization of the polyvinyl alcohol is preferably 500 or more and 8,000 or less, more preferably 700 or more and 8,000 or less, still more preferably 1,000 or more and 6,000 or less, still more preferably 1,500 or more and 6,000.
  • the saponification degree of the polyvinyl alcohol is preferably 80 mol% or more, more preferably 85 mol% or more, still more preferably 90 mol% or more, still more preferably 95 mol% or more, and 100 mol% or less.
  • the content of component (B) in the composition is preferably 0.01% by mass or more and 20% by mass or less, more preferably 0.02% by mass or more and 15% by mass or less, and still more preferably 0.05% by mass or more. 15% by mass or less, more preferably 0.1% by mass or more and 10% by mass or less, even more preferably 0.2% by mass or more and 5% by mass or less, still more preferably 0.2% by mass or more and 3% by mass or less,
  • the composition further contains water, and the water content in the composition is preferably 40% by mass or more, more preferably 70% by mass or more, still more preferably 80% by mass or more, and even more preferably 85% by mass. % or more, more preferably 90% by mass or more, still more preferably 95% by mass or more, and preferably 99.95% by mass or less, any one of ⁇ 1> to ⁇ 13> Skin external agent.
  • the total content of component (A) and water in the composition is preferably 70.05% by mass or more, more preferably 75% by mass or more, still more preferably 80% by mass or more, and even more preferably 85% by mass or more. , Still more preferably 90% by mass or more, still more preferably 95% by mass or more, and 100% by mass or less, any one of ⁇ 1> to ⁇ 14>.
  • ⁇ 16> The external preparation for skin according to any one of ⁇ 1> to ⁇ 15>, wherein the composition further contains a polyol.
  • ⁇ 17> The external preparation for skin according to ⁇ 16>, wherein the polyol satisfies a logPow value of -2.0 or more, which is an octanol/water partition coefficient.
  • the polyol is propylene glycol (1,2-propanediol), 1,3-propanediol, dipropylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,3 -butanediol, 1,2-pentanediol, 1,5-pentanediol, 1,2-hexanediol, 2,5-hexanediol, 1,6-hexanediol, 1,2-heptanediol, 1,7- Heptanediol, 1,2-octanediol, 1,8-octanediol, 1,2-nonanediol, 1,9-nonanediol, 1,2-decanediol, 1,10-decanediol, 1,2-dodecane Diol, 1,12-dodecanediol, 1,
  • the content of the polyol in the composition is preferably 0.05% by mass or more and 50% by mass or less, more preferably 0.1% by mass or more and 50% by mass or less, and still more preferably 0.5% by mass or more and 30% by mass. % by mass or less, more preferably 1.0% by mass or more and 30% by mass or less, even more preferably 1.5% by mass or more and 20% by mass or less, still more preferably 2.0% by mass or more and 20% by mass or less ,
  • the skin external preparation according to any one of ⁇ 16> to ⁇ 18>.
  • the composition is a pH adjuster, preferably an inorganic alkali agent, more preferably one or more selected from the group consisting of alkali metal hydroxides and alkaline earth metal hydroxides, and more preferably alkali metal metal water.
  • the skin according to any one of ⁇ 1> to ⁇ 19>, which contains an oxide, more preferably one or more selected from the group consisting of sodium hydroxide and potassium hydroxide, and still more preferably sodium hydroxide. External agents.
  • the metal ion concentration in the composition is preferably 0.002 mol/L or more and 0.80 mol/L or less, more preferably 0.002 mol/L or more and 0.50 mol/L or less, and still more preferably 0.005 mol/L or more.
  • 0.50 mol/L or less more preferably 0.01 mol/L or more and 0.30 mol/L or less, still more preferably 0.02 mol/L or more and 0.20 mol/L or less, ⁇ 1> to ⁇ 20>
  • the skin external preparation according to any one of 1.
  • the content of monoalcohols having 4 or less carbon atoms in the composition is preferably 60% by mass or less, more preferably 50% by mass or less, even more preferably 40% by mass or less, still more preferably 30% by mass or less, and more More preferably 10% by mass or less, still more preferably 5.0% by mass or less, still more preferably 1.0% by mass or less, still more preferably 0.05% by mass or less, and more
  • the external preparation for skin according to any one of ⁇ 1> to ⁇ 21>, which is more preferably less than 0.01% by mass, and most preferably substantially 0% by mass.
  • the content of the organic acid or its salt (C) other than the component (A) in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, and even more preferably is 3% by mass or less, even more preferably 1% by mass or less, even more preferably 0.5% by mass or less, even more preferably less than 0.5% by mass, and even more preferably less than 0.1% by mass;
  • the external preparation for skin according to any one of ⁇ 1> to ⁇ 22>, which is most preferably substantially 0% by mass.
  • the mass ratio [(C)/(A)] of an organic acid other than component (A) or a salt thereof (C) to component (A) in the composition is preferably less than 1, more preferably 0.8 or less, more preferably 0.6 or less, even more preferably 0.5 or less, still more preferably 0.3 or less, still more preferably 0.2 or less, still more preferably 0.1 or less, more
  • the topical skin preparation according to ⁇ 23> which is more preferably 0.05 or less, still more preferably 0.01 or less, and even more preferably substantially 0.
  • the content of the fungicide in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 3% by mass or less, and even more preferably 1% by mass. % or less, more preferably 0.07 mass % or less, still more preferably 0.05 mass % or less, still more preferably 0.03 mass % or less, and even more preferably 0.05 mass % or less.
  • the external preparation for skin according to any one of ⁇ 1> to ⁇ 24>, which is less than 01% by mass, most preferably substantially 0% by mass.
  • composition contains a disinfectant, and the content of the disinfectant in the composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more.
  • the skin external preparation according to any one of 1.
  • the viscosity of the composition at 25° C. is preferably 1.0 mPa ⁇ s or more, more preferably 2.0 mPa ⁇ s or more, still more preferably 3.0 mPa ⁇ s or more, and preferably 30,000 mPa ⁇ s or less.
  • the metered discharge container for containing the composition is a stroke type and pump type pressure container, and the viscosity of the composition at 25° C.
  • the metered discharge container containing the composition is a stroke-type and spray-type push-type container, and the viscosity of the composition at 25° C. is more preferably 800 mPa ⁇ s or less, still more preferably 500 mPa ⁇ s or less.
  • the constant-dispensing container containing the composition is a squeeze-type press container, and the viscosity of the composition at 25° C. is more preferably 25,000 mPa ⁇ s or less, still more preferably 10,000 mPa ⁇ s or less.
  • the external preparation for skin according to ⁇ 27> which is s or more.
  • the metered discharge container for containing the composition is an electric dispenser type container, and the viscosity of the composition at 25° C. is more preferably 800 mPa ⁇ s or less, still more preferably 500 mPa ⁇ s or less, and still more preferably 300 mPa.
  • the pH of the composition at 25°C is preferably 3.5 to 5.0, more preferably 3.5 to 4.5, even more preferably 3.7 to 4.5.
  • ⁇ 33> The external preparation for skin according to any one of ⁇ 1> to ⁇ 32>, which is an embodiment of (I) or (II) below.
  • An external skin preparation comprising an external skin preparation composition contained in a metered discharge container,
  • the composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid, Among the acids present in the composition, when an acid present in an acid form is defined as the component (A1), the component (A1 ) content of 0.05 mg or more and 80 mg or less,
  • the component (A) is lactic acid or a salt thereof,
  • the mass ratio [(C)/(A)] of the organic acid other than the component (A) or a salt thereof (C) to the component (A) in the composition is less than 1;
  • An external preparation for skin wherein the composition has a pH of 3.5 or more and 5.0 or less at 25°C.
  • An external skin preparation comprising an external skin preparation composition contained in a metered discharge container,
  • the composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid, Among the acids present in the composition, when an acid present in an acid form is defined as the component (A1), the component (A1 ) content of 0.05 mg or more and 80 mg or less,
  • the composition further contains a nonionic thickener (B),
  • An external preparation for skin wherein the composition has a viscosity of 100 mPa ⁇ s or more and 10,000 mPa ⁇ s or less at 25°C. ⁇ 34> The viscosity at 25° C.
  • the external skin preparation composition used in the external skin preparation of the aspect (II) is preferably 100 mPa ⁇ s or more and 5,000 mPa ⁇ s or less, more preferably 100 mPa ⁇ s or more and 8,000 mPa ⁇ s. s or less, more preferably 100 mPa s or more and 2,000 mPa s or less, even more preferably 100 mPa s or more and 1,000 mPa s or less, still more preferably 100 mPa s or more and 800 mPa s or less. , and more preferably 100 mPa ⁇ s or more and 700 mPa ⁇ s or less, the external preparation for skin according to ⁇ 33>.
  • ⁇ 35> The external preparation for skin according to any one of ⁇ 1> to ⁇ 34>, wherein the composition is liquid, gel, cream, or foam.
  • ⁇ 36> The external skin preparation according to any one of ⁇ 1> to ⁇ 35>, wherein the external skin preparation is a leave-on skin preparation, preferably a leave-on skin preparation for fingers.
  • An external skin product comprising an external skin preparation composition contained in a metered discharge container,
  • the composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid, Among the acids present in the composition, when an acid present in an acid form is used as the component (A1), the component (A1 ) content is 0.05 mg or more and 80 mg or less.
  • the step of supplying to the site among the acids present in the composition, when the acid present in the acid form is (A1), it is discharged from the fixed amount discharge container by one discharge operation.
  • a step in which the content of component (A1) in the composition is 0.05 mg or more and 80 mg or less
  • the sodium ion concentration of the external skin preparation composition was obtained by calculation from the blended amount of the pH adjuster (sodium hydroxide aqueous solution with a concentration of 1 mol/L).
  • the metal ions contained in the compositions of Examples and Comparative Examples are considered to be only sodium ions.
  • viscosity The viscosity of the external skin preparation composition was measured three times at 25° C. using a vibrating viscometer ("VM-10AL" manufactured by Sekonic Co., Ltd.), and the average value was obtained.
  • the measurement conditions according to the target viscosity are as follows: ⁇ Viscosity: 1 to 100mPa ⁇ s Jig M1, rotation speed 60 rpm ⁇ Viscosity over 100 mPa ⁇ s and 1,000 mPa ⁇ s or less Jig M2, rotation speed 30 rpm ⁇ Viscosity over 1,000 mPa s and 10,000 mPa s or less Jig M3, rotation speed 12 rpm ⁇ Viscosity over 10,000 mPa s and 100,000 mPa s or less Jig M4, rotation speed 6 rpm
  • pH The pH of the external skin preparation composition was measured at 25° C. using an electrode 6367-10D (manufactured by Horiba, Ltd.).
  • the content (% by mass) of the component (A1) in the external skin preparation composition is defined as, among acids derived from the component (A) present in the composition, the component (A1), which exists in an acid form, is dissociated.
  • the component (A2) is present in the form, it is obtained from the following formula.
  • Content (% by mass) of component (A1) in external skin preparation composition content (% by mass) of component (A) in composition ⁇ ⁇ molar ratio in composition [(A1)/ ⁇ (A1 ) + (A2)] ⁇
  • the content (mg) of the component (A1) in the ejected composition is determined by the following formula.
  • the "molar ratio [(A1)/ ⁇ (A1)+(A2)] in the composition” is obtained by the following calculation.
  • the molar amount of component (A1) is denoted as "HA”
  • the molar amount of component (A2) is denoted as " A- ".
  • the component (A) consists of a plurality of components
  • the following calculation method is defined in the present invention.
  • the molar ratio of each component [(A1) / ⁇ (A1) + (A2)] demand.
  • the molar ratio [(A1) / ⁇ (A1) + (A2)] in each component can be obtained.
  • Examples 1 to 12 Comparative Examples 1 to 8 (Preparation and Evaluation of External Skin Preparation Composition) After blending each component in the amount shown in Tables 1 and 2 and mixing at room temperature, using a hydrochloric acid aqueous solution with a concentration of 1 mol / L and / or a sodium hydroxide aqueous solution with a concentration of 1 mol / L as a pH adjuster A skin external preparation composition was prepared by adjusting the pH as described.
  • the blending amounts shown in Tables 1 and 2 are the active ingredient amounts (% by mass) of each component. After containing this skin external preparation composition in a metered discharge container, the amount shown in Tables 1 and 2 was discharged, and the following model experiment was conducted.
  • compositions shown in Tables 1 and 2 were applied to the skin surface in an amount corresponding to the condition of spreading over the entire palms of both hands by the method described later.
  • amount corresponding to the condition of spreading over the entire palms of both hands refers to the amount obtained by dividing the discharged composition amount (g) by 500 cm 2 , which is the average area of the palms of both hands.
  • the value of the average palm area of 500 cm 2 of both hands is obtained from Hyuk Choi et al., ⁇ Palm surface area database and estimation formula in Korean children using the alginate method'' (Applied Ergonomics, Vol.42 (2011), 873-882). It is a value estimated based on the value of TPSA (total palm surface area mean palm area with fingers) described in Table 2, which is the arithmetic mean value of the surface area of one hand. More specifically, the arithmetic mean of the total TPSA value (cm 2 ) for men and the total TPSA value (cm 2 ) for women shown in Table 2 is calculated, and double this value is measured on the palms of both hands. average area.
  • TPSA total palm surface area mean palm area with fingers
  • Lactic acid Fujifilm Wako Pure Chemical Co., Ltd. “lactic acid (active: 90%)”
  • Citric acid manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.
  • C2 Pyrrolidone carboxylic acid: manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.
  • pH adjuster hydrochloric acid aqueous solution with a concentration of 1 mol / L and / or with a concentration of 1 mol / L
  • Sodium hydroxide aqueous solution/hydrochloric acid aqueous solution FUJIFILM Wako Pure Chemical Co., Ltd.
  • Benzalkonium chloride "Benzalkonium chloride (50% aqueous solution)” manufactured by Tokyo Chemical Industry Co., Ltd.
  • the use of the external preparation for skin of this example has high bactericidal activity on the skin surface and can suppress skin irritation.
  • the skin external preparation composition used in this example unlike the benzalkonium chloride aqueous solution (Comparative Example 8), which is an existing disinfectant, was applied to the skin for some time. It can be seen that the bactericidal activity tends to improve rather than decrease as the temperature increases.
  • Examples 13-29 Ejection test of external skin preparation composition
  • a hydrochloric acid aqueous solution with a concentration of 1 mol / L and / or a sodium hydroxide aqueous solution with a concentration of 1 mol / L as a pH adjuster.
  • the pH was adjusted to prepare a skin external preparation composition.
  • the blending amount shown in Table 3 is the active ingredient amount (% by mass) of each component.
  • This external skin preparation composition was filled in a metered discharge container (stroke-type spray container X or pump container Y) shown in Table 3 to obtain a container-packed external skin preparation.
  • the filling amount of the skin external preparation composition was 50 mL in the spray container X and 120 mL in the pump container Y.
  • each ejection operation was performed once, and the amount of the composition ejected by one ejection operation was confirmed.
  • One discharge operation was performed by applying a load of 7 kg to the stroke of the metered discharge container for 3 seconds.
  • Example 16 ⁇ Using Fixed Dispensing Container X> 1: More squeaky than in Example 13 2: Slightly more squeaky than in Example 13 3: Equivalent to Example 13 4: Slightly less squeaky than in Example 13 5: Less squeaky than in Example 13 ⁇ When using the fixed quantity discharge container Y> 1: More squeaky than in Example 16 2: Slightly more squeaky than in Example 16 3: Equivalent to Example 16 4: Slightly less squeaky than in Example 16 5: Less squeaky than in Example 16
  • Lactic acid Fujifilm Wako Pure Chemical Co., Ltd. “lactic acid (active: 90%)”
  • B1 Polyvinyl alcohol: “JC-40” manufactured by Japan Vinyl Acetate & Poval Co., Ltd., polymerization degree 4,000, ken value 99.0 to 99.5 mol%
  • B2 Hydroxyethyl cellulose 1: "Natrosol HEC 250HHX” manufactured by Ashland Co., Ltd.

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Abstract

An external skin preparation comprising a constant-amount ejection container and an external skin preparation composition held therein, wherein the composition includes (A) either at least one acid selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid or salt(s) thereof. When any of the acid compounds in the composition which is present in acid form is taken as component (A1), then the amount of the component (A1) contained in the composition ejected from the constant-amount ejection container by one ejecting operation is 0.05-80 mg.

Description

皮膚外用剤Skin topical agent
　本発明は、皮膚外用剤に関する。 The present invention relates to an external preparation for skin.
　近年の調査によれば、人の日常生活における菌又はウイルスの感染経路としては接触感染が多いことが知られてきている。接触感染は主として、菌又はウイルスの感染者、ドアノブ、ハンドル、食器、玩具、その他日用品、内装品等の被接触物に手指が接触することにより起こる。 According to recent surveys, it is becoming known that contact infection is often the route of infection for bacteria or viruses in people's daily lives. Contact infection is mainly caused by the hands and fingers coming into contact with objects such as bacteria or virus infected persons, doorknobs, handles, tableware, toys, other daily necessities, and interior goods.
　このような日常生活での接触行動による菌又はウイルスの接触感染を予防する方法が求められている。
　手指を介しての菌又はウイルスの接触感染を予防する方法として、手指にアルコール系消毒剤等を適用して殺菌消毒する方法が知られている。しかしながら、殺菌乃至消毒成分として用いられるエタノール等のアルコールは揮発性が高く、手指に殺菌、殺ウイルス効果を付与するという観点では効果の持続性が充分ではなかった。 There is a demand for a method for preventing contact infection with bacteria or viruses due to such contact behavior in daily life.
As a method for preventing contact infection of bacteria or viruses through fingers, a method of sterilizing and disinfecting the fingers by applying an alcohol-based disinfectant or the like is known. However, alcohol such as ethanol used as a sterilizing or disinfecting component is highly volatile, and the durability of the effect is not sufficient from the viewpoint of imparting bactericidal and virucidal effects to hands and fingers.
　そこで、予め手指に菌又はウイルスに対する防御機能を付与する方法が検討されている。当該方法によれば、菌又はウイルスへの感染防止効果が継続して得られるので、外出先などで手洗い場がない環境下でも接触感染を予防することができる。特に、菌又はウイルスが付着した被接触物に繰り返し接触した場合でも感染を防止できる点で好ましい。 Therefore, methods of giving the fingers a protective function against bacteria or viruses in advance are being studied. According to this method, since the effect of preventing infection with bacteria or viruses can be continuously obtained, it is possible to prevent contact infection even in an environment where there is no hand-washing place, such as when going out. In particular, it is preferable in that infection can be prevented even when the object to be contacted with bacteria or viruses is repeatedly brought into contact with the object.
　特表２０１９－５１８７２０号公報（特許文献１）には、ナイアシンアミドまたはその誘導体；塩化ジデシルジメチルアンモニウムを含む第１の第４級アンモニウム塩；塩化ベンゼトニウム、塩化ベンザルコニウム、ポリジアリルジメチルアンモニウムクロライド等の第２の第４級アンモニウム塩；及び、化粧品として許容される基剤を含む手指消毒剤組成物等の局所組成物が、長期間持続する抗菌効果を提供できることが開示されている。 Japanese National Publication of International Patent Application No. 2019-518720 (Patent Document 1) discloses niacinamide or a derivative thereof; a first quaternary ammonium salt containing didecyldimethylammonium chloride; benzethonium chloride, benzalkonium chloride, polydiallyldimethylammonium chloride a second quaternary ammonium salt such as; and a cosmetically acceptable base.
　本発明は、下記に関する。
［１］皮膚外用剤組成物が定量吐出容器に収容されてなる皮膚外用剤であって、
　前記組成物は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を含有し、
　該組成物中に存在する前記酸のうち、酸型で存在するものを成分（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の前記成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である、皮膚外用剤。
［２］乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を皮膚表面の適用部位に供給する方法であって、下記工程（Ｉ）及び工程（ＩＩ）を順に有する、方法。
工程（Ｉ）：前記適用部位を洗浄する工程
工程（ＩＩ）：前記成分（Ａ）を含有する組成物が収容された定量吐出容器から該組成物を１回の吐出操作により吐出して前記適用部位に供給する工程であって、該組成物中に存在する前記酸のうち、酸型で存在するものを（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の前記成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である、工程 The present invention relates to the following.
[1] An external skin preparation comprising an external skin preparation composition contained in a metered discharge container,
The composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid,
Among the acids present in the composition, when an acid present in an acid form is defined as the component (A1), the component (A1 ) content is 0.05 mg or more and 80 mg or less.
[2] A method of supplying one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid to an application site on the skin surface, comprising the following steps (I) and (II) ) in order.
Step (I): The step of washing the application site Step (II): The composition containing the component (A) is discharged from a metered discharge container containing the composition by one discharge operation, and the application is performed. In the step of supplying to the site, among the acids present in the composition, when the acid existing in the acid form is (A1), it is discharged from the fixed amount discharge container by one discharge operation. the content of the component (A1) in the composition is 0.05 mg or more and 80 mg or less;
　特許文献１の開示技術において使用される殺菌剤及び抗菌剤は、人体への安全性等の観点から、皮膚用の組成物中への配合量が実質的に制限される。そのため、殺菌剤又は抗菌剤による皮膚の殺菌又は殺ウイルス活性については充分なものとはいえず、さらなる改善が望まれていた。
　本発明は、優れた殺菌又は殺ウイルス性を発揮し、且つ、皮膚刺激性の低い皮膚外用剤を提供することを課題とする。 The bactericidal agent and antibacterial agent used in the technique disclosed in Patent Document 1 are substantially limited in amount to be incorporated into the composition for skin from the viewpoint of safety to the human body. Therefore, the bactericidal or virucidal activity of the skin by the bactericidal agent or antibacterial agent is not sufficient, and further improvement has been desired.
An object of the present invention is to provide an external preparation for skin that exhibits excellent bactericidal or virucidal properties and has low skin irritation.
　本発明者らは、所定の有機酸又はその塩を含有する皮膚外用剤組成物を、所定要件を満たすように吐出し得る容器に収容してなる皮膚外用剤を用いることで、上記課題を解決できることを見出した。 The present inventors have solved the above problems by using an external skin preparation containing a composition containing a predetermined organic acid or a salt thereof in a container that can be discharged so as to satisfy predetermined requirements. I found what I can do.
　本発明によれば、優れた殺菌又は殺ウイルス性を発揮し、且つ、皮膚刺激性の低い皮膚外用剤を提供できる。 According to the present invention, it is possible to provide an external preparation for skin that exhibits excellent bactericidal or virucidal properties and has low skin irritation.
［定義］
　本明細書において「酸型で存在する成分（Ａ１）」とは、成分（Ａ）に由来する乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸のうち、組成物中で乳酸、ピルビン酸及びウロカニン酸として存在する成分を意味する。また以下の記載において、成分（Ａ）に由来する乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸のうち、組成物中で乳酸イオン、ピルビン酸イオン及びウロカニン酸イオンとして存在する成分を「解離型で存在する成分（Ａ２）」ともいう。 [definition]
As used herein, the term “component (A1) existing in an acid form” refers to one or more acids selected from the group consisting of lactic acid, pyruvic acid and urocanic acid derived from component (A) in the composition. It means the components present as lactic acid, pyruvic acid and urocanic acid. In addition, in the following description, one or more acids selected from the group consisting of lactic acid, pyruvic acid and urocanic acid derived from component (A) are present in the composition as lactate ion, pyruvate ion and urocanate ion. The component that does so is also referred to as "a component that exists in a dissociated form (A2)".
　本明細書において「殺菌又は殺ウイルス性」とは、皮膚外用剤組成物を適用した皮膚表面の殺菌又は殺ウイルス性を意味する。例えばセラチア菌に対する殺菌性は、具体的には実施例に記載の方法により評価することができる。その他の菌及びウイルスに対する殺菌、殺ウイルス性は、技術常識を参酌して評価することができる。 As used herein, "bactericidal or virucidal" means bactericidal or virucidal of the skin surface to which the external skin composition is applied. For example, bactericidal activity against Serratia can be specifically evaluated by the method described in Examples. The bactericidal and virucidal properties against other bacteria and viruses can be evaluated in consideration of common technical knowledge.
　本明細書において「殺菌又は殺ウイルス性を発揮する」とは、（１）皮膚外用剤組成物を皮膚表面に適用した後に該皮膚表面に付着した菌・ウイルスに対して発現される殺菌・殺ウイルス効果、（２）皮膚に付着した菌・ウイルスに対し、組成物を適用することにより発現される殺菌・殺ウイルス効果、（３）皮膚を菌・ウイルスを媒介しない皮膚に整える効果、（４）皮膚を菌・ウイルスから保護し、衛生的に保つ効果、（５）皮膚を介した菌・ウイルスの伝播及び接触感染を防止する効果、及び（６）菌・ウイルスに対する皮膚の感染防御力を高める効果、等を付与する概念を包含するものである。 As used herein, the term "exhibiting bactericidal or virucidal properties" means (1) bactericidal/killing activity against bacteria/viruses adhering to the skin surface after the external skin preparation composition is applied to the skin surface. Viral effect, (2) Bactericidal and virucidal effect expressed by applying the composition to bacteria and viruses adhering to the skin, (3) Skin conditioning effect that does not mediate bacteria and viruses, (4) ) The effect of protecting the skin from bacteria and viruses and keeping it hygienic, (5) the effect of preventing the spread and contact infection of bacteria and viruses through the skin, and (6) the effect of protecting the skin from infection against bacteria and viruses. It includes the concept of imparting an effect to enhance, and the like.
［皮膚外用剤］
　本発明の皮膚外用剤は、皮膚外用剤組成物（以下、単に「組成物」ともいう）が定量吐出容器に収容されてなる皮膚外用剤であって、前記組成物は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を含有し、該組成物中に存在する前記酸のうち、酸型で存在するものを成分（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の前記成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である皮膚外用剤である。
　すなわち、本発明の皮膚外用剤は、前記皮膚外用剤組成物と、前記定量吐出容器とからなる皮膚外用製品を意味する。
　本発明の皮膚外用剤は上記構成を有することにより、優れた殺菌又は殺ウイルス性を発揮し、且つ、皮膚刺激性が低いものである。 [External preparation for skin]
The external skin preparation of the present invention is an external skin preparation comprising an external skin preparation composition (hereinafter also simply referred to as "composition") contained in a metered discharge container, wherein the composition comprises lactic acid, pyruvic acid and When one or more acids selected from the group consisting of urocanic acid or salts thereof (A) are contained, and among the acids present in the composition, those present in an acid form are used as the component (A1) and an external preparation for skin, wherein the content of the component (A1) in the composition discharged from the fixed quantity discharge container by one discharge operation is 0.05 mg or more and 80 mg or less.
That is, the external preparation for skin of the present invention means a product for external use for skin comprising the above-mentioned external preparation for skin composition and the above-mentioned metered discharge container.
The external preparation for skin of the present invention exhibits excellent bactericidal or virucidal properties and has low skin irritation by having the above constitution.
　本発明の皮膚外用剤が上記効果を奏する理由については定かではないが、次のように考えられる。
　本発明の皮膚外用剤は、殺菌又は殺ウイルス成分として成分（Ａ）を用いたものである。成分（Ａ）である乳酸、ピルビン酸及びウロカニン酸は、汗腺から供給されるなどして本来ヒトの皮膚上に存在しており、特に手指上において、菌、ウイルス等に対する殺菌、殺ウイルス機能を担っていることを本発明者らは知見した。そのため、成分（Ａ）を含有する皮膚外用剤組成物は殺菌又は殺ウイルス性を有しながらも、皮膚刺激性が少なく、人体安全性の高い組成物とすることができると考えられる。
　上記の殺菌又は殺ウイルス性に関して、成分（Ａ）を含有する組成物においても、ｐＨが低い方が殺菌又は殺ウイルス性が高いことは知られている。例えば成分（Ａ）である乳酸は、水溶液中で酸型（ＣＨ３ＣＨ（ＯＨ）ＣＯＯＨ）と解離型（ＣＨ３ＣＨ（ＯＨ）ＣＯＯ－）の形態を取り得るが、酸型の方が電荷をもたず、菌又はウイルス内に取り込まれやすいことから、酸型の方が高い殺菌又は殺ウイルス性を発現すると考えられる。 Although the reason why the external preparation for skin of the present invention exhibits the above effects is not clear, it is considered as follows.
The external preparation for skin of the present invention uses component (A) as a bactericidal or virucidal component. Lactic acid, pyruvic acid, and urocanic acid, which are components (A), are originally present on the human skin as supplied from sweat glands, and especially on the fingers, they have bactericidal and virucidal functions against bacteria, viruses, etc. The inventors of the present invention have found that Therefore, it is thought that the composition for external use on the skin containing the component (A) has bactericidal or virucidal properties, is less irritating to the skin, and is highly safe for the human body.
Regarding the above bactericidal or virucidal properties, it is known that compositions containing component (A) also have higher bactericidal or virucidal properties when the pH is lower. For example, lactic acid, which is component (A), can take an acid form (CH 3 CH(OH)COOH) and a dissociated form (CH 3 CH(OH)COO − ) in an aqueous solution, but the acid form is more charged. It is thought that the acid form exhibits higher bactericidal or virucidal properties because it does not have a
　その一方で、成分（Ａ）を含有する組成物においても、低ｐＨ領域の組成物では皮膚刺激性を生じる懸念がある。
　そこで本発明者らは、皮膚に適用される皮膚外用剤組成物中の前記酸のうち、酸型で存在する成分（Ａ１）の含有量に着目した。そして、成分（Ａ）を含有する皮膚外用剤組成物を定量吐出容器に収容し、該容器から１回の吐出操作により吐出される組成物中の成分（Ａ１）を所定の範囲とすることで、優れた殺菌又は殺ウイルス性を発揮し、且つ、皮膚刺激性を低減できることを見出した。 On the other hand, even in the composition containing the component (A), there is a concern that the composition in the low pH range may cause skin irritation.
Therefore, the present inventors paid attention to the content of the component (A1) present in the acid form among the acids in the external skin preparation composition applied to the skin. Then, the external skin preparation composition containing the component (A) is accommodated in a metered discharge container, and the component (A1) in the composition discharged from the container by one discharge operation is within a predetermined range. , It has been found that it can exhibit excellent bactericidal or virucidal properties and can reduce skin irritation.
　本発明の皮膚外用剤は、前記皮膚外用剤組成物が前記定量吐出容器に収容されてなるものであり、該定量吐出容器から１回の吐出操作により吐出される組成物中に含まれる成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である。吐出される組成物中の成分（Ａ１）の含有量が上記範囲であることにより、優れた殺菌又は殺ウイルス性を発揮し、且つ、皮膚刺激性の低い皮膚外用剤となる。また、本発明の皮膚外用剤は、１回の吐出操作により「吐出される組成物中に含まれる成分（Ａ１）の含有量」が上記範囲となるよう制御されるものであるため、優れた殺菌又は殺ウイルス性を発揮しつつも、皮膚への低刺激性を実現する量となる成分（Ａ１）を、簡便かつ安定的に皮膚に供給できる。 The external skin preparation of the present invention comprises the external skin preparation composition contained in the quantitative discharge container, and the components ( The content of A1) is 0.05 mg or more and 80 mg or less. When the content of the component (A1) in the discharged composition is within the above range, the external preparation for skin exhibits excellent bactericidal or virucidal properties and is less irritating to the skin. In addition, the external preparation for skin of the present invention is excellent because "the content of the component (A1) contained in the composition to be discharged" is controlled to be within the above range by one discharging operation. It is possible to easily and stably supply the component (A1) to the skin in an amount that achieves low irritation to the skin while exhibiting bactericidal or virucidal properties.
　定量吐出容器から１回の吐出操作により吐出される組成物中の成分（Ａ１）の含有量は、殺菌又は殺ウイルス性向上の観点から、好ましくは０．１ｍｇ以上、より好ましくは０．２ｍｇ以上、さらに好ましくは０．４ｍｇ以上、よりさらに好ましくは０．５ｍｇ以上、よりさらに好ましくは１．０ｍｇ以上、よりさらに好ましくは２．０ｍｇ以上であり、組成物を連続して皮膚に連用しても皮膚刺激性を抑制しやすくする観点から、好ましくは６０ｍｇ以下、より好ましくは５０ｍｇ以下、さらに好ましくは４５ｍｇ以下である。そして、定量吐出容器から１回の吐出操作により吐出される組成物中の成分（Ａ１）の含有量は、０．０５ｍｇ以上８０ｍｇ以下であり、好ましくは０．１ｍｇ以上６０ｍｇ以下、より好ましくは０．２ｍｇ以上６０ｍｇ以下、さらに好ましくは０．４ｍｇ以上５０ｍｇ以下、よりさらに好ましくは０．５ｍｇ以上５０ｍｇ以下、よりさらに好ましくは１．０ｍｇ以上４５ｍｇ以下、よりさらに好ましくは２．０ｍｇ以上４５ｍｇ以下である。
　１回の吐出操作により吐出される組成物中の成分（Ａ１）の含有量は、実施例に記載の方法により算出することができる。 The content of the component (A1) in the composition discharged from the metered discharge container by one discharge operation is preferably 0.1 mg or more, more preferably 0.2 mg or more, from the viewpoint of improving sterilization or virucidal properties. , more preferably 0.4 mg or more, still more preferably 0.5 mg or more, still more preferably 1.0 mg or more, still more preferably 2.0 mg or more, even if the composition is continuously applied to the skin From the viewpoint of easily suppressing skin irritation, it is preferably 60 mg or less, more preferably 50 mg or less, and even more preferably 45 mg or less. The content of component (A1) in the composition discharged from the metered discharge container by one discharge operation is 0.05 mg or more and 80 mg or less, preferably 0.1 mg or more and 60 mg or less, more preferably 0 mg. 2 mg or more and 60 mg or less, more preferably 0.4 mg or more and 50 mg or less, even more preferably 0.5 mg or more and 50 mg or less, even more preferably 1.0 mg or more and 45 mg or less, still more preferably 2.0 mg or more and 45 mg or less .
The content of the component (A1) in the composition ejected by one ejection operation can be calculated by the method described in Examples.
　１回の吐出操作により吐出される組成物中の成分（Ａ１）の含有量は、本発明の皮膚外用剤に用いる組成物中の成分（Ａ）の含有量、組成物のｐＨ、組成物の粘度、及び定量吐出容器の種類及び１回の吐出操作による吐出量、又はこれらの組み合わせにより制御できる。 The content of component (A1) in the composition ejected by one ejection operation is the content of component (A) in the composition used for the external skin preparation of the present invention, the pH of the composition, and the It can be controlled by the viscosity, the type of the metered discharge container, the discharge amount by one discharge operation, or a combination thereof.
　本発明の皮膚外用剤において、前記定量吐出容器から１回の吐出操作により吐出される前記組成物の量は、殺菌又は殺ウイルス性向上の観点、及び皮膚への塗布性向上の観点から、好ましくは０．０５ｇ以上、より好ましくは０．１ｇ以上、さらに好ましくは０．２ｇ以上であり、皮膚刺激性を抑制する観点、及び皮膚への塗布後のたれ落ちを抑制する観点から、好ましくは３．０ｇ以下、より好ましくは２．５ｇ以下、さらに好ましくは２．０ｇ以下である。そして、前記定量吐出容器から１回の吐出操作により吐出される前記組成物の量は、好ましくは０．０５ｇ以上３．０ｇ以下、より好ましくは０．１ｇ以上２．５ｇ以下、さらに好ましくは０．２ｇ以上２．０ｇ以下である。 In the external preparation for skin of the present invention, the amount of the composition discharged from the metered discharge container in one discharge operation is preferable from the viewpoint of improving the bactericidal or virucidal properties and improving the applicability to the skin. is 0.05 g or more, more preferably 0.1 g or more, and still more preferably 0.2 g or more, and from the viewpoint of suppressing skin irritation and dripping after application to the skin, preferably 3 0 g or less, more preferably 2.5 g or less, and even more preferably 2.0 g or less. The amount of the composition discharged from the fixed quantity discharge container in one discharge operation is preferably 0.05 g or more and 3.0 g or less, more preferably 0.1 g or more and 2.5 g or less, and still more preferably 0 g. .2 g or more and 2.0 g or less.
＜定量吐出容器＞
　本発明の皮膚外用剤は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を含有する皮膚外用剤組成物が定量吐出容器に収容されてなるものである。
　本明細書において「定量吐出容器」とは、皮膚外用剤組成物を収容することが可能な容器であって、容器の内容物である皮膚外用剤組成物を、吐出操作を行うことにより略一定量吐出することが可能な容器をいう。 <Fixed-volume dispensing container>
The external preparation for skin of the present invention comprises an external preparation for skin composition containing one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid, contained in a metered discharge container. is.
As used herein, the term “quantitative discharge container” refers to a container capable of containing an external skin preparation composition. A container that can dispense a large amount of liquid.
　定量吐出容器としては、ストローク式、スクイーズ式等の押圧式容器；電動ディスペンサー式容器；等が挙げられる。また、１回使い切りの個包装タイプの容器も、本発明における定量吐出容器に包含されるものとする。
　押圧式容器のうち、ストローク式の押圧式容器としてはポンプタイプ、スプレータイプの容器が挙げられ、特開２０１９－５１９４９号公報に記載のストローク式の押圧式容器等を例示できる。またスクイーズ式の押圧式容器としては、特開２００１－１５１２８３号公報に記載のスクイーズ式の押圧式容器等を例示できる。
　電動ディスペンサー式容器としては、例えば、センサー部に手をかざすことで自動的に内容物が一定量吐出される機構を備えた容器が挙げられる。 Examples of fixed-quantity discharge containers include press-type containers such as stroke-type and squeeze-type containers; electric dispenser-type containers; and the like. In addition, a single-use, individually-wrapped container is also included in the metered-discharge container of the present invention.
Among press-type containers, examples of stroke-type press-type containers include pump-type and spray-type containers. As the squeeze-type push-type container, the squeeze-type push-type container described in Japanese Patent Application Laid-Open No. 2001-151283 can be exemplified.
Examples of the electric dispenser type container include a container equipped with a mechanism that automatically discharges a certain amount of the content when a hand is held over a sensor portion.
　本明細書においては、定量吐出容器の１回の吐出操作を以下のように定義する。
　定量吐出容器がストローク式の押圧式容器である場合には、１回の吐出操作とは、該容器をフルストロークで１回押圧する操作である。ここでいうフルストロークとは、ストロークにより７ｋｇの荷重を３秒間かけた状態を意味する。
　定量吐出容器がスクイーズ式の押圧式容器である場合には、１回の吐出操作とは、該容器の押圧部を１回押圧してスクイーズ変形させる操作である。ここでいうスクイーズ変形とは、押圧により７ｋｇの荷重を３秒間かけた状態を意味する。また容器の押圧部とは、容器の形状によっても異なるが、例えば容器の側面外周部を意味する。
　定量吐出容器が     電動ディスペンサーである場合には、１回の吐出操作とは、例えば、容器の内容物の吐出を制御するセンサー部に１回手をかざす操作である。 In the present specification, one discharge operation of the fixed quantity discharge container is defined as follows.
In the case where the fixed quantity dispensing container is a stroke-type pressing container, one discharging operation is an operation of pressing the container once with a full stroke. The full stroke here means a state in which a load of 7 kg is applied for 3 seconds by stroke.
In the case where the fixed quantity dispensing container is a squeeze-type push-type container, one discharge operation is an operation of pressing the pressing portion of the container once to squeeze and deform the container. The squeeze deformation as used herein means a state in which a load of 7 kg is applied for 3 seconds by pressing. Further, the pressing portion of the container means, for example, the side peripheral portion of the container, although it varies depending on the shape of the container.
When the fixed quantity dispensing container is an electric dispenser, one dispensing operation is, for example, an operation of holding a hand once over a sensor unit that controls the dispensing of the contents of the container.
　複数回の吐出を想定した定量吐出容器の容量は特に制限されないが、皮膚外用剤組成物を収容する観点から、通常、５ｍＬ以上、２，０００ｍＬ以下の範囲である。 Although the volume of the fixed-quantity discharge container assuming multiple discharges is not particularly limited, it is usually in the range of 5 mL or more and 2,000 mL or less from the viewpoint of containing the external skin preparation composition.
＜皮膚外用剤組成物＞
　本発明の皮膚外用剤に用いる皮膚外用剤組成物（以下、本発明における皮膚外用剤組成物又は本発明における組成物ともいう）は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を含有する組成物である。該組成物は前記定量吐出容器に収容され、定量吐出容器から吐出して用いられる。 <External skin preparation composition>
The external skin preparation composition used in the external skin preparation of the present invention (hereinafter also referred to as the external skin preparation composition of the present invention or the composition of the present invention) is one selected from the group consisting of lactic acid, pyruvic acid and urocanic acid. A composition containing the above acid or salt thereof (A). The composition is housed in the fixed quantity discharge container and discharged from the fixed quantity discharge container for use.
（成分（Ａ））
　成分（Ａ）は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩である。成分（Ａ）は殺菌又は殺ウイルス成分として作用する。
　乳酸、ピルビン酸及びウロカニン酸の塩としては、乳酸又はピルビン酸の、カリウム塩、ナトリウム塩等のアルカリ金属塩；カルシウム塩、マグネシウム塩等のアルカリ土類金属塩；アミン塩；アンモニウム塩等が挙げられる。これらの中でも、殺菌又は殺ウイルス性向上の観点、並びに入手容易性の観点から、乳酸、ピルビン酸及びウロカニン酸の、アルカリ金属塩及びアルカリ土類金属塩からなる群から選ばれる１種以上が好ましく、カリウム塩、ナトリウム塩、及びカルシウム塩からなる群から選ばれる１種以上がより好ましく、乳酸カリウム、乳酸ナトリウム、及び乳酸カルシウムからなる群から選ばれる１種以上がさらに好ましい。
　殺菌又は殺ウイルス性向上の観点から、成分（Ａ）としては乳酸又はその塩が好ましく、乳酸、乳酸カリウム、乳酸ナトリウム、及び乳酸カルシウムからなる群から選ばれる１種以上がより好ましく、乳酸を含むことがさらに好ましい。
　成分（Ａ）が乳酸を含む場合、成分（Ａ）全量中における乳酸又はその塩の含有量は、殺菌又は殺ウイルス性向上の観点から、好ましくは８０質量％以上であり、より好ましくは９０質量％以上であり、最も好ましくは１００質量％である。 (Component (A))
Component (A) is one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid and urocanic acid. Component (A) acts as a bactericidal or virucidal component.
Examples of salts of lactic acid, pyruvic acid and urocanic acid include alkali metal salts such as potassium salts and sodium salts of lactic acid or pyruvic acid; alkaline earth metal salts such as calcium salts and magnesium salts; amine salts; and ammonium salts. be done. Among these, one or more selected from the group consisting of alkali metal salts and alkaline earth metal salts of lactic acid, pyruvic acid and urocanic acid is preferable from the viewpoint of improving bactericidal or virucidal properties and easy availability. , potassium salts, sodium salts, and calcium salts, and more preferably one or more selected from the group consisting of potassium lactate, sodium lactate, and calcium lactate.
From the viewpoint of improving bactericidal or virucidal properties, component (A) is preferably lactic acid or a salt thereof, more preferably one or more selected from the group consisting of lactic acid, potassium lactate, sodium lactate, and calcium lactate, and contains lactic acid. is more preferred.
When component (A) contains lactic acid, the content of lactic acid or a salt thereof in the total amount of component (A) is preferably 80% by mass or more, more preferably 90% by mass, from the viewpoint of improving bactericidal or virucidal properties. % or more, and most preferably 100% by mass.
　本発明における組成物中の成分（Ａ）の含有量は、殺菌又は殺ウイルス性向上の観点から、好ましくは０．０５質量％以上、より好ましくは０．１質量％以上、さらに好ましくは０．２質量％以上、よりさらに好ましくは０．３質量％以上、よりさらに好ましくは０．５質量％以上である。また、皮膚刺激性を抑制する観点から、好ましくは１５質量％以下、より好ましくは１０質量％以下、さらに好ましくは５．０質量％以下、よりさらに好ましくは４．０質量％以下、よりさらに好ましくは３．０質量％以下、よりさらに好ましくは２．５質量％以下、よりさらに好ましくは２．０質量％以下である。そして、組成物中の成分（Ａ）の含有量は、好ましくは０．０５質量％以上１５質量％以下、より好ましくは０．０５質量％以上１０質量％以下、さらに好ましくは０．１質量％以上１０質量％以下、さらに好ましくは０．２質量％以上５．０質量％以下、よりさらに好ましくは０．３質量％以上４．０質量％以下、よりさらに好ましくは０．５質量％以上３．０質量％以下、よりさらに好ましくは０．５質量％以上２．５質量％以下、よりさらに好ましくは０．５質量％以上２．０質量％以下である。
　なお本明細書において、成分（Ａ）が塩を含む場合、「成分（Ａ）の含有量」とは、前記酸（「酸型で存在する成分（Ａ１）」及び「解離型で存在する成分（Ａ２）」）の量と、前記塩の量を解離型へ換算した量との合算量をいう。 The content of component (A) in the composition of the present invention is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, and still more preferably 0.1% by mass or more, from the viewpoint of improving bactericidal or virucidal properties. It is 2% by mass or more, more preferably 0.3% by mass or more, and even more preferably 0.5% by mass or more. In addition, from the viewpoint of suppressing skin irritation, it is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 5.0% by mass or less, even more preferably 4.0% by mass or less, and even more preferably is 3.0% by mass or less, more preferably 2.5% by mass or less, and even more preferably 2.0% by mass or less. The content of component (A) in the composition is preferably 0.05% by mass or more and 15% 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. 10% by mass or less, more preferably 0.2% by mass or more and 5.0% by mass or less, even more preferably 0.3% by mass or more and 4.0% by mass or less, still more preferably 0.5% by mass or more and 3 0 mass % or less, more preferably 0.5 mass % or more and 2.5 mass % or less, and even more preferably 0.5 mass % or more and 2.0 mass % or less.
In this specification, when the component (A) contains a salt, the "content of the component (A)" refers to the acid ("the component present in the acid form (A1)" and "the component present in the dissociated form (A2)") and the amount obtained by converting the amount of the salt into the dissociated form.
　本発明における組成物中の成分（Ａ１）の含有量は、殺菌又は殺ウイルス性向上の観点から、好ましくは０．０２質量％以上、より好ましくは０．０４質量％以上、さらに好ましくは０．０５質量％以上、よりさらに好ましくは０．１質量％以上、よりさらに好ましくは０．２質量％以上、よりさらに好ましくは０．３質量％以上である。また、皮膚刺激性を抑制する観点から、好ましくは１０質量％以下、より好ましくは５．０質量％以下、さらに好ましくは４．０質量％以下、よりさらに好ましくは３．０質量％以下、よりさらに好ましくは２．５質量％以下、よりさらに好ましくは２．０質量％以下、よりさらに好ましくは１．０質量％以下である。そして、本発明における組成物中の成分（Ａ１）の含有量は、好ましくは０．０２質量％以上１０質量％以下、より好ましくは０．０４質量％以上５．０質量％以下、さらに好ましくは０．０５質量％以上４．０質量％以下、よりさらに好ましくは０．１質量％以上３．０質量％以下、よりさらに好ましくは０．２質量％以上２．５質量％以下、よりさらに好ましくは０．３質量％以上２．０質量％以下、よりさらに好ましくは０．３質量％以上１．０質量％以下である。 The content of component (A1) in the composition of the present invention is preferably 0.02% by mass or more, more preferably 0.04% by mass or more, and still more preferably 0.04% by mass or more, from the viewpoint of improving bactericidal or virucidal properties. 05% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.2% by mass or more, and even more preferably 0.3% by mass or more. In addition, from the viewpoint of suppressing skin irritation, the It is more preferably 2.5% by mass or less, even more preferably 2.0% by mass or less, and even more preferably 1.0% by mass or less. The content of component (A1) in the composition of the present invention is preferably 0.02% by mass or more and 10% by mass or less, more preferably 0.04% by mass or more and 5.0% by mass or less, and still more preferably 0.05% by mass or more and 4.0% by mass or less, more preferably 0.1% by mass or more and 3.0% by mass or less, still more preferably 0.2% by mass or more and 2.5% by mass or less, still more preferably is 0.3% by mass or more and 2.0% by mass or less, more preferably 0.3% by mass or more and 1.0% by mass or less.
　本発明における組成物中の成分（Ａ１）の含有量は、本発明における組成物中に存在する前記成分（Ａ）に由来する酸のうち、酸型で存在するものを成分（Ａ１）、解離型で存在するものを成分（Ａ２）とした場合に、下記式より算出することができる。
　　組成物中の成分（Ａ１）の含有量（質量％）＝組成物中の成分（Ａ）の含有量（質量％）×組成物中のモル比［（Ａ１）／｛（Ａ１）＋（Ａ２）｝］
　ここで、「組成物中のモル比［（Ａ１）／｛（Ａ１）＋（Ａ２）｝］」とは、組成物中に存在する成分（Ａ１）及び成分（Ａ２）の合計に対する成分（Ａ１）のモル比を意味し、本発明における具体的には実施例に記載の方法により算出することができる。
　組成物中のモル比［（Ａ１）／｛（Ａ１）＋（Ａ２）｝］は、殺菌又は殺ウイルス性向上の観点から、好ましくは０．２以上、より好ましくは０．３以上、さらに好ましくは０．４以上である。また、皮膚刺激性を抑制する観点から、好ましくは０．６以下、より好ましくは０．５５以下、さらに好ましくは０．５以下である。そして、組成物中に存在する前記成分（Ａ）に由来する酸のうち、酸型で存在するものを成分（Ａ１）、解離型で存在するものを成分（Ａ２）とした場合に、組成物中のモル比［（Ａ１）／｛（Ａ１）＋（Ａ２）｝］は、好ましくは０．２以上０．６以下、より好ましくは０．３以上０．５５以下、さらに好ましくは０．４以上０．５以下である。 The content of the component (A1) in the composition of the present invention is such that among the acids derived from the component (A) present in the composition of the present invention, those present in the acid form are the components (A1), dissociated When the component (A2) is present in the form, it can be calculated from the following formula.
Content (% by mass) of component (A1) in the composition = content (% by mass) of component (A) in the composition x molar ratio in the composition [(A1) / {(A1) + (A2 )}]
Here, the "molar ratio [(A1) / {(A1) + (A2)}] in the composition" refers to the total of component (A1) and component (A2) present in the composition (A1 ), which can be specifically calculated by the method described in Examples in the present invention.
The molar ratio [(A1)/{(A1)+(A2)}] in the composition is preferably 0.2 or more, more preferably 0.3 or more, and still more preferably from the viewpoint of improving bactericidal or virucidal properties. is 0.4 or more. From the viewpoint of suppressing skin irritation, it is preferably 0.6 or less, more preferably 0.55 or less, and even more preferably 0.5 or less. Then, among the acids derived from the component (A) present in the composition, when the acid present in the acid form is the component (A1) and the acid present in the dissociated form is the component (A2), the composition The molar ratio [(A1) / {(A1) + (A2)}] is preferably 0.2 to 0.6, more preferably 0.3 to 0.55, and still more preferably 0.4 0.5 or less.
（成分（Ｂ）：ノニオン性増粘剤）
　皮膚外用剤組成物は、使用感を向上させる観点から、さらに成分（Ｂ）として、ノニオン性増粘剤を含有することができる。本明細書において「使用感が良好」とは、皮膚外用剤組成物を皮膚に適用し乾燥させた後、水で濡らした際にきしみ感が少なく、感触が良好であることを意味する。
　本発明の組成物に用いる成分（Ｂ）は、使用感を向上させる観点、殺菌又は殺ウイルス性を向上又は維持する観点、及び、組成物への溶解性を向上させる観点から、水溶性のノニオン性増粘剤であることが好ましい。当該成分（Ｂ）の具体例としては、ヒドロキシブチルメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ヒドロキシエチルセルロース等のセルロースエーテル類；プロピレングリコールアルギネート、ポリビニルアルコール、ポリビニルピロリドン、ヒドロキシプロピルグアーガム、ローカストビーンガム、アミロース、ヒドロキシエチルアミロース、澱粉又はその誘導体等が挙げられ、これらのうち１種又は２種以上を用いることができる。
　上記の中でも、殺菌又は殺ウイルス性を維持する観点、及び、組成物の使用感を向上させる観点から、成分（Ｂ）は好ましくはセルロースエーテル類及びポリビニルアルコールからなる群から選ばれる１種以上であり、より好ましくはヒドロキシブチルメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ヒドロキシエチルセルロース、及びポリビニルアルコールからなる群から選ばれる１種以上、さらに好ましくはヒドロキシエチルセルロース及びポリビニルアルコールからなる群から選ばれる１種以上、よりさらに好ましくはヒドロキシエチルセルロースである。 (Component (B): nonionic thickener)
The skin external preparation composition can further contain a nonionic thickener as component (B) from the viewpoint of improving the feeling of use. In the present specification, the term "good feeling in use" means that the composition for external use for skin is applied to the skin, dried, and then moistened with water with little squeaky feeling and good feel.
The component (B) used in the composition of the present invention is a water-soluble nonion from the viewpoint of improving the feeling of use, improving or maintaining the bactericidal or virucidal properties, and improving the solubility in the composition. It is preferably a viscous thickener. Specific examples of the component (B) include cellulose ethers such as hydroxybutylmethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and hydroxyethylcellulose; propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropyl guar gum, locust bean gum, and amylose. , hydroxyethyl amylose, starch or derivatives thereof, and the like, and one or more of these can be used.
Among the above, the component (B) is preferably one or more selected from the group consisting of cellulose ethers and polyvinyl alcohol from the viewpoint of maintaining the bactericidal or virucidal properties and improving the feeling of use of the composition. more preferably one or more selected from the group consisting of hydroxybutylmethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, and polyvinyl alcohol, more preferably one or more selected from the group consisting of hydroxyethylcellulose and polyvinyl alcohol , and more preferably hydroxyethyl cellulose.
　成分（Ｂ）として用いられるポリビニルアルコールの重合度は、組成物の使用感を向上させる観点から、好ましくは５００以上、より好ましくは７００以上、さらに好ましくは１，０００以上、よりさらに好ましくは１，５００以上、よりさらに好ましくは２，０００以上であり、組成物の吐出性の観点から、好ましくは８，０００以下、より好ましくは６，０００以下、さらに好ましくは５，０００以下である。そして、ポリビニルアルコールの重合度は、好ましくは５００以上８，０００以下、より好ましくは７００以上８，０００以下、さらに好ましくは１，０００以上６，０００以下、よりさらに好ましくは１，５００以上６，０００以下、よりさらに好ましくは２，０００以上５，０００以下である。
　ポリビニルアルコールのケン価度は特に制限されないが、組成物の使用感を向上させる観点から、好ましくは８０モル％以上、より好ましくは８５モル％以上、さらに好ましくは９０モル％以上、よりさらに好ましくは９５モル％以上であり、１００モル％以下である。 The polymerization degree of the polyvinyl alcohol used as the component (B) is preferably 500 or more, more preferably 700 or more, still more preferably 1,000 or more, and still more preferably 1,000 or more, from the viewpoint of improving the feeling of use of the composition. It is 500 or more, more preferably 2,000 or more, preferably 8,000 or less, more preferably 6,000 or less, and still more preferably 5,000 or less from the viewpoint of the ejection property of the composition. The degree of polymerization of polyvinyl alcohol is preferably 500 or more and 8,000 or less, more preferably 700 or more and 8,000 or less, still more preferably 1,000 or more and 6,000 or less, and even more preferably 1,500 or more and 6,000 or less. 000 or less, more preferably 2,000 or more and 5,000 or less.
Although the saponification degree of polyvinyl alcohol is not particularly limited, it is preferably 80 mol% or more, more preferably 85 mol% or more, still more preferably 90 mol% or more, still more preferably from the viewpoint of improving the feeling of use of the composition. It is 95 mol % or more and 100 mol % or less.
　成分（Ｂ）として、市販のノニオン性増粘剤を用いることもできる。ヒドロキシエチルセルロースとしては、Ａｓｈｌａｎｄ（株）製「Ｎａｔｒｏｓｏｌ　ＨＥＣ　２５０ＨＨＸ」、（株）ダイセル製「ＨＥＣ　ダイセル　８５０ＳＥ」等、ポリビニルアルコールとしては、日本酢ビ・ポバール（株）製「ＪＣ－４０」等が挙げられる。 A commercially available nonionic thickener can also be used as component (B). Examples of hydroxyethyl cellulose include "Natrosol HEC 250HHX" manufactured by Ashland and "HEC Daicel 850SE" manufactured by Daicel. be done.
　成分（Ｂ）を用いる場合、本発明における組成物中の成分（Ｂ）の含有量は、組成物の使用感向上の観点から、好ましくは０．０１質量％以上、より好ましくは０．０２質量％以上、さらに好ましくは０．０５質量％以上、よりさらに好ましくは０．１質量％以上、よりさらに好ましくは０．２質量％以上であり、本発明における組成物の吐出性、及び、殺菌又は殺ウイルス性を向上又は維持する観点から、好ましくは２０質量％以下、より好ましくは１５質量％以下、さらに好ましくは１０質量％以下、よりさらに好ましくは５質量％以下、よりさらに好ましくは３質量％以下、よりさらに好ましくは１質量％以下、よりさらに好ましくは０．５質量％以下である。そして、本発明における組成物中の成分（Ｂ）の含有量は、好ましくは０．０１質量％以上２０質量％以下、より好ましくは０．０２質量％以上１５質量％以下、さらに好ましくは０．０５質量％以上１５質量％以下、よりさらに好ましくは０．１質量％以上１０質量％以下、よりさらに好ましくは０．２質量％以上５質量％以下、よりさらに好ましくは０．２質量％以上３質量％以下、よりさらに好ましくは０．２質量％以上１質量％以下、よりさらに好ましくは０．２質量％以上０．５質量％以下である。 When component (B) is used, the content of component (B) in the composition in the present invention is preferably 0.01% by mass or more, more preferably 0.02% by mass, from the viewpoint of improving the feeling of use of the composition. % or more, more preferably 0.05% by mass or more, still more preferably 0.1% by mass or more, and even more preferably 0.2% by mass or more, and the ejection property of the composition in the present invention, and the sterilization or From the viewpoint of improving or maintaining virucidal properties, the content is preferably 20% by mass or less, more preferably 15% by mass or less, even more preferably 10% by mass or less, even more preferably 5% by mass or less, and even more preferably 3% by mass. Below, more preferably 1% by mass or less, and even more preferably 0.5% by mass or less. The content of component (B) in the composition of the present invention is preferably 0.01% by mass or more and 20% by mass or less, more preferably 0.02% by mass or more and 15% by mass or less, and still more preferably 0.02% by mass or more and 15% by mass or less. 05% by mass or more and 15% by mass or less, more preferably 0.1% by mass or more and 10% by mass or less, still more preferably 0.2% by mass or more and 5% by mass or less, still more preferably 0.2% by mass or more and 3 % by mass or less, more preferably 0.2% by mass or more and 1% by mass or less, and even more preferably 0.2% by mass or more and 0.5% by mass or less.
（水）
　本発明における皮膚外用剤組成物は、成分（Ａ）を溶解させる観点、及び組成物の吐出性向上の観点から、さらに水を含有することが好ましい。該組成物中の水の含有量は、成分（Ａ）を溶解させる観点、及び吐出性向上の観点から、好ましくは４０質量％以上、より好ましくは７０質量％以上、さらに好ましくは８０質量％以上、よりさらに好ましくは８５質量％以上、よりさらに好ましくは９０質量％以上、よりさらに好ましくは９５質量％以上であり、また、好ましくは９９．９５質量％以下である。 (water)
From the viewpoint of dissolving the component (A) and improving the ejection property of the composition, the external skin preparation composition of the present invention preferably further contains water. The content of water in the composition is preferably 40% by mass or more, more preferably 70% by mass or more, and still more preferably 80% by mass or more, from the viewpoint of dissolving the component (A) and improving the dischargeability. , more preferably 85% by mass or more, still more preferably 90% by mass or more, still more preferably 95% by mass or more, and preferably 99.95% by mass or less.
　本発明における皮膚外用剤組成物中の成分（Ａ）及び水の合計含有量は、本発明の効果を得る観点、成分（Ａ）の溶解性の観点、及び吐出性向上の観点から、好ましくは７０．０５質量％以上、より好ましくは７５質量％以上、さらに好ましくは８０質量％以上、よりさらに好ましくは８５質量％以上、よりさらに好ましくは９０質量％以上、よりさらに好ましくは９５質量％以上であり、また、１００質量％以下である。 The total content of component (A) and water in the external skin preparation composition of the present invention is preferably 70.05% by mass or more, more preferably 75% by mass or more, still more preferably 80% by mass or more, even more preferably 85% by mass or more, still more preferably 90% by mass or more, and even more preferably 95% by mass or more There is, and it is 100 mass % or less.
（ポリオール）
　本発明における皮膚外用剤組成物は、該組成物の極性を皮膚表面の極性に近づけ、皮膚へ塗り広げやすく、意図する塗布面においてムラなく殺菌又は殺ウイルス成分を発揮させる観点から、さらにポリオールを含有することができる。 (polyol)
The external composition for skin of the present invention has a polarity close to that of the skin surface, is easily spreadable on the skin, and exhibits a bactericidal or virucidal component evenly on the intended application surface, and further contains a polyol. can contain.
　ポリオールとしては、オクタノール／水分配係数であるｌｏｇＰｏｗ値が－２．０以上を満たすものが好ましく利用できる。ｌｏｇＰｏｗ値が高いほど疎水性が高いことを示し、かかるポリオールを所定量組成物に含有させることで、組成物を疎水化し、純水よりも皮膚に馴染みやすくすることが期待できる。
　ここで、
　　Ｐｏｗ：１－オクタノールと水の２つの溶媒相中にポリオールを加えて平衡状態となった時の、その２つの溶媒相におけるポリオールの濃度比
　　ｌｏｇＰｏｗ＝ｌｏｇ１０（１－オクタノール相中のポリオールの濃度／水相中のポリオールの濃度）
である。
　ポリオールのｌｏｇＰｏｗ値は、Ｒｅｎｘｉａｏ　Ｗａｎｇ　ｅｔ　ａｌ．,　Ｊ．Ｃｈｅｍ．Ｉｎｆ．Ｍｏｄｅｌ．２００７，Ｖｏｌ．４７，ｐｐ．２１４０に記載のアルゴリズム「ＸＬＯＧＰ３」を使用して計算値を求めることができる。 As the polyol, those satisfying a logPow value of -2.0 or more, which is the octanol/water partition coefficient, can be preferably used. A higher logPow value indicates higher hydrophobicity, and by including a predetermined amount of such a polyol in the composition, it can be expected that the composition will be made hydrophobic and will be more compatible with the skin than pure water.
here,
Pow: The concentration ratio of the polyol in the two solvent phases when the polyol is added to the two solvent phases of 1-octanol and water to reach an equilibrium logPow = log10 (concentration of polyol in the 1-octanol phase / Concentration of polyol in aqueous phase)
is.
The logPow values of polyols are calculated according to Renxiao Wang et al. , J. Chem. Inf. Model. 2007, Vol. 47, pp. 2140 can be used to determine the calculated value.
　ポリオールの具体例としては、プロピレングリコール（１，２－プロパンジオール）、１，３－プロパンジオール、ジプロピレングリコール、１，２－ブチレングリコール、１，３－ブチレングリコール、１，４－ブチレングリコール、２，３－ブタンジオール、１，２－ペンタンジオール、１，５－ペンタンジオール、１，２－ヘキサンジオール、２，５－ヘキサンジオール、１，６－ヘキサンジオール、１，２－ヘプタンジオール、１，７－ヘプタンジオール、１，２－オクタンジオール、１，８－オクタンジオール、１，２－ノナンジオール、１，９－ノナンジオール、１，２－デカンジオール、１，１０－デカンジオール、１，２－ドデカンジオール、１，１２－ドデカンジオール、１，２－テトラデカンジオール、１，２－ヘキサデカンジオール、１，１６－ヘキサデカンジオール等の直鎖状ジオール；
グリセリン、１，２，３－ブタントリオール、１，２，４－ブタントリオール、１，２，５－ペンタントリオール、１，２，６－ヘキサントリオール、１，２，７－ヘプタントリオール、１，２，８－オクタントリオール、１，２，９－ノナントリオール、１，２，１０－デカントリオール等の直鎖状トリオール；
２－メチル－１，３－プロパンジオール、２，２－ジメチル－１，３－プロパンジオール、３－メチル－１，３－ブタンジオール、２－メチルペンタン－２，４－ジオール、２－エチル－１，３－ヘキサンジオール、トリプロピレングリコール、２－ブチル－２－エチル－１，３－プロパンジオール、３－（２－エチルヘキシルオキシ）－１，２－プロパンジオール、（ラウリル／ミリスチル）グリコールヒドロキシプロピルエーテル、３，７，１１，１５－テトラメチルヘキサデカン－１，２，３－トリオール等の分岐鎖状ジオール又はトリオール；及び、
ポリエチレングリコール、ポリグリセリン、ＰＰＧ－１０ブタンジオール等のポリマー；等が挙げられ、これらのうち１種又は２種以上を用いることができる。 Specific examples of polyols include propylene glycol (1,2-propanediol), 1,3-propanediol, dipropylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,3-butanediol, 1,2-pentanediol, 1,5-pentanediol, 1,2-hexanediol, 2,5-hexanediol, 1,6-hexanediol, 1,2-heptanediol, 1 ,7-heptanediol, 1,2-octanediol, 1,8-octanediol, 1,2-nonanediol, 1,9-nonanediol, 1,2-decanediol, 1,10-decanediol, 1, Linear diols such as 2-dodecanediol, 1,12-dodecanediol, 1,2-tetradecanediol, 1,2-hexadecanediol, and 1,16-hexadecanediol;
glycerin, 1,2,3-butanetriol, 1,2,4-butanetriol, 1,2,5-pentanetriol, 1,2,6-hexanetriol, 1,2,7-heptanetriol, 1,2 ,8-octanetriol, 1,2,9-nonanetriol, linear triols such as 1,2,10-decanetriol;
2-methyl-1,3-propanediol, 2,2-dimethyl-1,3-propanediol, 3-methyl-1,3-butanediol, 2-methylpentane-2,4-diol, 2-ethyl- 1,3-hexanediol, tripropylene glycol, 2-butyl-2-ethyl-1,3-propanediol, 3-(2-ethylhexyloxy)-1,2-propanediol, (lauryl/myristyl) glycol hydroxypropyl branched diols or triols such as ethers, 3,7,11,15-tetramethylhexadecane-1,2,3-triol; and
polymers such as polyethylene glycol, polyglycerin, PPG-10 butanediol; and the like, and one or more of these can be used.
　本発明における皮膚外用剤組成物がポリオールを含有する場合、皮膚外用剤組成物中のポリオールの含有量は、皮膚へ塗り広げやすく、意図する塗布面においてムラなく殺菌又は殺ウイルス成分を発揮させる観点から、好ましくは０．０５質量％以上、より好ましくは０．１質量％以上、さらに好ましくは０．５質量％以上、よりさらに好ましくは１．０質量％以上であり、よりさらに好ましくは１．５質量％以上、よりさらに好ましくは２．０質量％以上であり、また、塗布時のべたつき低減の観点から、好ましくは５０％質量％以下、より好ましくは３０質量％以下、さらに好ましくは２０質量％以下である。そして、皮膚外用剤組成物中のポリオールの含有量は、好ましくは０．０５質量％以上５０％質量％以下、より好ましくは０．１質量％以上５０％質量％以下、さらに好ましくは０．５質量％以上３０質量％以下、よりさらに好ましくは１．０質量％以上３０質量％以下、よりさらに好ましくは１．５質量％以上２０質量％以下、よりさらに好ましくは２．０質量％以上２０質量％以下である。 When the topical skin preparation composition of the present invention contains a polyol, the content of the polyol in the topical skin preparation composition is such that it can be easily spread over the skin and the bactericidal or virucidal component can be exhibited evenly on the intended application surface. Therefore, it is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.5% by mass or more, still more preferably 1.0% by mass or more, and still more preferably 1.0% by mass or more. 5% by mass or more, more preferably 2.0% by mass or more, and from the viewpoint of reducing stickiness during application, preferably 50% by mass or less, more preferably 30% by mass or less, and further preferably 20% by mass. % or less. The polyol content in the external skin preparation composition is preferably 0.05% by mass or more and 50% by mass or less, more preferably 0.1% by mass or more and 50% by mass or less, and still more preferably 0.5% by mass. % by mass or more and 30% by mass or less, more preferably 1.0% by mass or more and 30% by mass or less, even more preferably 1.5% by mass or more and 20% by mass or less, still more preferably 2.0% by mass or more and 20% by mass % or less.
（ｐＨ調整剤）
　本発明における皮膚外用剤組成物は、ｐＨを好適範囲に調整する観点で、ｐＨ調整剤を含有することが好ましい。
　ｐＨ調整剤は、組成物のｐＨを所望の範囲に調整できる成分であればよく、例えば、酸成分、アルカリ成分、緩衝剤成分等を用いることができる。これらの中でも、成分（Ａ）を含有する組成物の２５℃におけるｐＨを後述する範囲（好ましくは３．５以上）とする観点から、ｐＨ調整剤として、少なくともアルカリ成分を用いることが好ましい。
　該アルカリ成分としては、有機アルカリ剤、無機アルカリ剤のいずれも用いることができるが、水への溶解性、入手容易性及び経済性の観点から、好ましくは無機アルカリ剤である。
　無機アルカリ剤としては、水酸化ナトリウム、水酸化カリウム、水酸化カルシウム等の金属水酸化物、炭酸ナトリウム、炭酸水素ナトリウム等の金属炭酸塩等が挙げられ、これらのうち１種又は２種以上を用いることができる。これらの中でも、入手容易性及び経済性の観点から、好ましくはアルカリ金属の水酸化物及びアルカリ土類金属の水酸化物からなる群から選ばれる１種以上であり、より好ましくはアルカリ金属の金属水酸化物であり、さらに好ましくは水酸化ナトリウム及び水酸化カリウムからなる群から選ばれる１種以上であり、よりさらに好ましくは水酸化ナトリウムである。
　皮膚外用剤組成物がｐＨ調整剤を含有する場合、組成物中のｐＨ調整剤の含有量は、組成物のｐＨを所望の範囲に調整できる量であればよい。 (pH adjuster)
The skin external preparation composition of the present invention preferably contains a pH adjuster from the viewpoint of adjusting the pH to a suitable range.
The pH adjuster may be any component as long as it can adjust the pH of the composition to a desired range, and examples thereof include acid components, alkali components, buffer components, and the like. Among these, it is preferable to use at least an alkaline component as a pH adjuster from the viewpoint of adjusting the pH of the composition containing component (A) at 25° C. to the range described below (preferably 3.5 or higher).
As the alkali component, either an organic alkali agent or an inorganic alkali agent can be used, but the inorganic alkali agent is preferable from the viewpoints of solubility in water, availability and economy.
Examples of inorganic alkaline agents include metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide, metal carbonates such as sodium carbonate and sodium hydrogen carbonate, and the like. can be used. Among these, from the viewpoint of availability and economy, it is preferably one or more selected from the group consisting of alkali metal hydroxides and alkaline earth metal hydroxides, more preferably alkali metal metals It is a hydroxide, more preferably one or more selected from the group consisting of sodium hydroxide and potassium hydroxide, and still more preferably sodium hydroxide.
When the external skin preparation composition contains a pH adjuster, the content of the pH adjuster in the composition may be an amount that can adjust the pH of the composition to a desired range.
（金属イオン濃度）
　本発明において、本発明における皮膚外用剤組成物中の成分（Ａ１）の含有割合を高める観点からは、本発明における皮膚外用剤組成物中の成分（Ａ）の含有量を高めることが好ましい。さらに、皮膚外用剤組成物中の成分（Ａ）の含有量を高めた場合にも、ｐＨを目的範囲内に制御する観点から、皮膚外用剤組成物には、アルカリ金属の水酸化物及びアルカリ土類金属の水酸化物からなる群から選ばれる１種以上が好適に用いられる。アルカリ金属の水酸化物、及びアルカリ土類金属の水酸化物については前記の通りである。
　アルカリ金属の水酸化物及びアルカリ土類金属の水酸化物からなる群から選ばれる１種以上が用いられる結果、皮膚外用剤組成物中の金属イオン濃度は、好ましくは０．００２ｍｏｌ／Ｌ以上、より好ましくは０．００５ｍｏｌ／Ｌ以上、さらに好ましくは０．０１ｍｏｌ／Ｌ以上、よりさらに好ましくは０．０２ｍｏｌ／Ｌ以上となる。一方で、皮膚外用剤組成物中の金属イオン濃度は、皮膚のミネラルバランス維持の観点から、好ましくは０．８０ｍｏｌ／Ｌ以下、より好ましくは０．５０ｍｏｌ／Ｌ以下、さらに好ましくは０．３０ｍｏｌ／Ｌ以下、よりさらに好ましくは０．２０ｍｏｌ／Ｌ以下である。そして、皮膚外用剤組成物中の金属イオン濃度は、好ましくは０．００２ｍｏｌ／Ｌ以上０．８０ｍｏｌ／Ｌ以下、より好ましくは０．００２ｍｏｌ／Ｌ以上０．５０ｍｏｌ／Ｌ以下、さらに好ましくは０．００５ｍｏｌ／Ｌ以上０．５０ｍｏｌ／Ｌ以下、よりさらに好ましくは０．０１ｍｏｌ／Ｌ以上０．３０ｍｏｌ／Ｌ以下、よりさらに好ましくは０．０２ｍｏｌ／Ｌ以上０．２０ｍｏｌ／Ｌ以下である。 (metal ion concentration)
In the present invention, from the viewpoint of increasing the content of component (A1) in the external skin preparation composition of the present invention, it is preferable to increase the content of component (A) in the external skin preparation composition of the present invention. Furthermore, even when the content of component (A) in the external skin preparation composition is increased, from the viewpoint of controlling the pH within the target range, the external skin preparation composition contains an alkali metal hydroxide and an alkali One or more selected from the group consisting of hydroxides of earth metals is preferably used. Alkali metal hydroxides and alkaline earth metal hydroxides are as described above.
As a result of using one or more selected from the group consisting of alkali metal hydroxides and alkaline earth metal hydroxides, the metal ion concentration in the external skin preparation composition is preferably 0.002 mol/L or more, More preferably 0.005 mol/L or more, still more preferably 0.01 mol/L or more, still more preferably 0.02 mol/L or more. On the other hand, the metal ion concentration in the skin external preparation composition is preferably 0.80 mol/L or less, more preferably 0.50 mol/L or less, still more preferably 0.30 mol/L, from the viewpoint of maintaining the mineral balance of the skin. L or less, more preferably 0.20 mol/L or less. The metal ion concentration in the external skin composition is preferably 0.002 mol/L or more and 0.80 mol/L or less, more preferably 0.002 mol/L or more and 0.50 mol/L or less, and still more preferably 0.002 mol/L or more and 0.50 mol/L or less. 005 mol/L or more and 0.50 mol/L or less, more preferably 0.01 mol/L or more and 0.30 mol/L or less, still more preferably 0.02 mol/L or more and 0.20 mol/L or less.
　本明細書において「皮膚外用剤組成物中の金属イオン濃度」とは、該組成物中に存在する全金属イオンの濃度を意味する。本発明に用いる組成物においては、主として、成分（Ａ）に包含される所定の有機酸塩に由来する金属イオン、及び前記ｐＨ調整剤に由来する金属イオンの濃度の合計である。
　一般に、組成物中に金属イオンが存在すると、塩化ベンザルコニウム等の殺菌剤の殺菌効果を阻害する傾向がある。しかしながら本発明に用いる皮膚外用剤組成物では、成分（Ａ）による殺菌又は殺ウイルス性が金属イオンにより阻害されることがないため、優れた殺菌又は殺ウイルス性を発揮できる。
　組成物中の金属イオン濃度は、イオン選択性電極法により測定することができる。 As used herein, the term "metal ion concentration in an external skin preparation composition" means the concentration of all metal ions present in the composition. In the composition used in the present invention, it is mainly the total concentration of the metal ions derived from the predetermined organic acid salt contained in the component (A) and the metal ions derived from the pH adjuster.
In general, the presence of metal ions in the composition tends to inhibit the bactericidal efficacy of bactericidal agents such as benzalkonium chloride. However, in the skin external preparation composition used in the present invention, the bactericidal or virucidal properties of the component (A) are not inhibited by metal ions, and thus excellent bactericidal or virucidal properties can be exhibited.
The metal ion concentration in the composition can be measured by an ion selective electrode method.
（その他の成分）
　本発明における皮膚外用剤組成物には、上記以外に、必要に応じて他の成分、例えば、界面活性剤、紫外線吸収剤、酸化防止剤、防腐剤、制汗剤、香料、保湿剤、感触調整剤、抗炎症剤等を含有させることもできる。 (other ingredients)
In addition to the above, the external skin preparation composition of the present invention may optionally contain other ingredients such as surfactants, ultraviolet absorbers, antioxidants, preservatives, antiperspirants, fragrances, moisturizers, and feel agents. Modulators, anti-inflammatory agents and the like can also be included.
　本発明における皮膚外用剤組成物は、成分（Ａ）を殺菌又は殺ウイルス成分として用いた組成物である観点で、エタノール、イソプロパノール等の炭素数４以下のモノアルコールを配合せずとも、殺菌又は殺ウイルス性を発現することができる。さらに、皮膚刺激性を抑制する観点から、該組成物中の炭素数４以下のモノアルコールの含有量は、好ましくは６０質量％以下、より好ましくは５０質量％以下、さらに好ましくは４０質量％以下、よりさらに好ましくは３０質量％以下、よりさらに好ましくは１０質量％以下であり、よりさらに好ましくは５．０質量％以下であり、よりさらに好ましくは１．０質量％以下であり、よりさらに好ましくは０．０５質量％以下であり、よりさらに好ましくは０．０１質量％未満であり、実質０質量％とすることが最も好ましい。 From the viewpoint of being a composition using component (A) as a bactericidal or virucidal component, the external skin preparation composition of the present invention does not contain a monoalcohol having 4 or less carbon atoms such as ethanol and isopropanol. It is capable of expressing virucidal properties. Furthermore, from the viewpoint of suppressing skin irritation, the content of monoalcohol having 4 or less carbon atoms in the composition is preferably 60% by mass or less, more preferably 50% by mass or less, and still more preferably 40% by mass or less. , Still more preferably 30% by mass or less, still more preferably 10% by mass or less, still more preferably 5.0% by mass or less, still more preferably 1.0% by mass or less, still more preferably is 0.05% by mass or less, more preferably less than 0.01% by mass, and most preferably substantially 0% by mass.
（成分（Ｃ）：成分（Ａ）以外の有機酸又はその塩）
　皮膚外用剤組成物は、成分（Ａ）を殺菌又は殺ウイルス成分として用いた組成物である観点で、成分（Ａ）以外の有機酸又はその塩（以下、「成分（Ｃ）」とも称する）を配合せずとも、殺菌又は殺ウイルス性を発現することができる。この観点、及び皮膚刺激性を抑制する観点から、組成物中の成分（Ａ）以外の有機酸又はその塩（Ｃ）の含有量は、好ましくは１５質量％以下、より好ましくは１０質量％以下、さらに好ましくは５質量％以下、よりさらに好ましくは３質量％以下、よりさらに好ましくは１質量％以下、よりさらに好ましくは０．５質量％以下、よりさらに好ましくは０．５質量％未満、よりさらに好ましくは０．１質量％未満であり、実質０質量％とすることが最も好ましい。
　なお本明細書において、成分（Ｃ）が有機酸塩である場合、「成分（Ｃ）の含有量」とは、該有機酸に換算した量をいう。 (Component (C): Organic acid or salt thereof other than component (A))
From the viewpoint of being a composition using component (A) as a bactericidal or virucidal component, the external skin preparation composition contains an organic acid other than component (A) or a salt thereof (hereinafter also referred to as "component (C)"). Bactericidal or virucidal properties can be expressed without blending. From this point of view and from the point of view of suppressing skin irritation, the content of the organic acid or its salt (C) other than the component (A) in the composition is preferably 15% by mass or less, more preferably 10% by mass or less. , more preferably 5% by mass or less, still more preferably 3% by mass or less, even more preferably 1% by mass or less, even more preferably 0.5% by mass or less, even more preferably less than 0.5% by mass, more It is more preferably less than 0.1% by mass, and most preferably substantially 0% by mass.
In this specification, when the component (C) is an organic acid salt, the "content of the component (C)" refers to the amount in terms of the organic acid.
　また、皮膚外用剤組成物中の、成分（Ａ）に対する、成分（Ａ）以外の有機酸又はその塩（Ｃ）の質量比［（Ｃ）／（Ａ）］は、殺菌又は殺ウイルス性を維持する観点、及び皮膚刺激性を抑制する観点から、好ましくは１未満であり、より好ましくは０．８以下、さらに好ましくは０．６以下、よりさらに好ましくは０．５以下、よりさらに好ましくは０．３以下、よりさらに好ましくは０．２以下、よりさらに好ましくは０．１以下、よりさらに好ましくは０．０５以下、よりさらに好ましくは０．０１以下であり、よりさらに好ましくは実質０である。 In addition, the mass ratio [(C)/(A)] of an organic acid other than component (A) or a salt thereof (C) to component (A) in the external skin preparation composition has bactericidal or virucidal properties. From the viewpoint of maintenance and the viewpoint of suppressing skin irritation, it is preferably less than 1, more preferably 0.8 or less, still more preferably 0.6 or less, even more preferably 0.5 or less, and still more preferably 0.3 or less, more preferably 0.2 or less, still more preferably 0.1 or less, still more preferably 0.05 or less, still more preferably 0.01 or less, and even more preferably substantially zero be.
　なお、成分（Ｃ）に相当する、成分（Ａ）以外の有機酸又はその塩としては、成分（Ａ）以外のカルボン酸系化合物、スルホン酸系化合物、又はこれらの塩が挙げられる。
　上記カルボン酸系化合物又はその塩としては、例えば、酢酸、プロピオン酸、ブタン酸等の、炭素数４以下の脂肪族モノカルボン酸；安息香酸等の芳香族モノカルボン酸；マロン酸、コハク酸、グルタル酸、アジピン酸、マレイン酸、フマル酸等の脂肪族ジカルボン酸；フタル酸、イソフタル酸等の芳香族ジカルボン酸；ポリグルタミン酸等のポリカルボン酸；リンゴ酸、グリコール酸、ヒドロキシアクリル酸、グリセリン酸、酒石酸、クエン酸等のヒドロキシカルボン酸；グルタミン酸、アスパラギン酸等の酸性アミノ酸；ピロリドンカルボン酸；又はこれらの塩が挙げられる。
　上記スルホン酸系化合物又はその塩としては、メタンスルホン酸、エタンスルホン酸等の脂肪族スルホン酸；ｐ－トルエンスルホン酸、ナフタレンスルホン酸等の芳香族スルホン酸；又はこれらの塩が挙げられる。
　上記有機酸の塩としては、カリウム塩、ナトリウム塩等のアルカリ金属塩；カルシウム塩、マグネシウム塩等のアルカリ土類金属塩；アミン塩；アンモニウム塩等が挙げられる。 Examples of organic acids other than component (A) or salts thereof corresponding to component (C) include carboxylic acid compounds other than component (A), sulfonic acid compounds, and salts thereof.
Examples of the carboxylic acid compounds or salts thereof include aliphatic monocarboxylic acids having 4 or less carbon atoms such as acetic acid, propionic acid and butanoic acid; aromatic monocarboxylic acids such as benzoic acid; malonic acid, succinic acid, Aliphatic dicarboxylic acids such as glutaric acid, adipic acid, maleic acid, fumaric acid; Aromatic dicarboxylic acids such as phthalic acid and isophthalic acid; Polycarboxylic acids such as polyglutamic acid; Malic acid, glycolic acid, hydroxyacrylic acid, glyceric acid hydroxycarboxylic acids such as , tartaric acid and citric acid; acidic amino acids such as glutamic acid and aspartic acid; pyrrolidonecarboxylic acid; or salts thereof.
Examples of the sulfonic acid compounds or salts thereof include aliphatic sulfonic acids such as methanesulfonic acid and ethanesulfonic acid; aromatic sulfonic acids such as p-toluenesulfonic acid and naphthalenesulfonic acid; and salts thereof.
Examples of the salt of the organic acid include alkali metal salts such as potassium salts and sodium salts; alkaline earth metal salts such as calcium salts and magnesium salts; amine salts; and ammonium salts.
　皮膚外用剤組成物は、成分（Ａ）を殺菌又は殺ウイルス成分として用いた組成物である観点で、塩化ベンザルコニウム、塩化ベンゼトニウム等の第四級アンモニウム塩；塩化アルキルジアミノエチルグリシン及びアルキルポリアミノエチルグリシン等の両性界面活性剤；クロルヘキシジングルコン酸等のビグアナイド；次亜塩素酸ナトリウム；グルタラール、フタラール、ホルマリン等のアルデヒド；ポピドンヨード；ヨードチンキ；フェノール；クレゾール石ケン液；過酢酸；オキシドール；等の殺菌剤を配合せずとも、殺菌又は殺ウイルス性を発現する。この観点、及び皮膚刺激性を抑制する観点から、該組成物中の殺菌剤の含有量は好ましくは１５質量％以下、より好ましくは１０質量％以下、さらに好ましくは５質量％以下、よりさらに好ましくは３質量％以下、よりさらに好ましくは１質量％以下であり、よりさらに好ましくは０．０７質量％以下であり、よりさらに好ましくは０．０５質量％以下であり、よりさらに好ましくは０．０３質量％以下であり、よりさらに好ましくは０．０１質量％未満であり、実質０質量％とすることが最も好ましい。一方、上記殺菌剤を配合する場合、殺菌又は殺ウイルス性向上の観点から、該組成物中の殺菌剤の含有量は好ましくは０．０１質量％以上、さらに好ましくは０．０５質量％以上である。
　また、成分（Ａ）に対する上記殺菌剤の質量比（殺菌剤／成分（Ａ））は、皮膚刺激性を抑制する観点から、好ましくは０．５以下、より好ましくは０．２以下、さらに好ましくは０．１以下、よりさらに好ましくは０．０５以下、よりさらに好ましくは０．０３以下、よりさらに好ましくは０．０１以下であり、実質０とすることが最も好ましい。一方、上記殺菌剤を配合する場合、殺菌又は殺ウイルス性向上の観点から、成分（Ａ）に対する上記殺菌剤の質量比（殺菌剤／成分（Ａ））は、好ましくは０．０１以上、より好ましくは０．０５以上である。
　なお、本明細書において、上述の殺菌剤であり、かつ界面活性剤としても働く剤は、殺菌剤であると定義する。 From the viewpoint of being a composition using component (A) as a bactericidal or virucidal component, the external skin preparation composition includes quaternary ammonium salts such as benzalkonium chloride and benzethonium chloride; alkyldiaminoethylglycine chlorides and alkylpolyamino chlorides; amphoteric surfactants such as ethylglycine; biguanides such as chlorhexidine gluconic acid; sodium hypochlorite; aldehydes such as glutaral, phthalal and formalin; It exhibits bactericidal or virucidal properties without adding any agents. From this point of view and the point of view of suppressing skin irritation, the content of the disinfectant in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, and even more preferably is 3% by mass or less, more preferably 1% by mass or less, even more preferably 0.07% by mass or less, still more preferably 0.05% by mass or less, and even more preferably 0.03 % by mass or less, more preferably less than 0.01% by mass, and most preferably substantially 0% by mass. On the other hand, when the above fungicide is blended, the content of the fungicide in the composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, from the viewpoint of improving bactericidal or virucidal properties. be.
In addition, the mass ratio of the disinfectant to component (A) (sterilant/component (A)) is preferably 0.5 or less, more preferably 0.2 or less, and still more preferably, from the viewpoint of suppressing skin irritation. is 0.1 or less, more preferably 0.05 or less, still more preferably 0.03 or less, still more preferably 0.01 or less, and is most preferably substantially 0. On the other hand, when the fungicide is blended, from the viewpoint of improving sterilization or virucidal properties, the mass ratio of the fungicide to component (A) (fungicide/component (A)) is preferably 0.01 or more, and more Preferably it is 0.05 or more.
In the present specification, the above-mentioned agent that is a bactericide and also acts as a surfactant is defined as a bactericide.
（粘度）
　皮膚外用剤組成物の２５℃における粘度は、定量吐出容器の吐出操作１回あたりの吐出量を均一化する観点、及び、皮膚への塗布性向上の観点から、好ましくは１．０ｍＰａ・ｓ以上、より好ましくは２．０ｍＰａ・ｓ以上、さらに好ましくは３．０ｍＰａ・ｓ以上であり、定量吐出容器による吐出性向上の観点、及び、殺菌又は殺ウイルス性を向上又は維持する観点から、好ましくは３０，０００ｍＰａ・ｓ以下、より好ましくは２５，０００ｍＰａ・ｓ以下、さらに好ましくは１０，０００ｍＰａ・ｓ以下、よりさらに好ましくは８，０００ｍＰａ・ｓ以下、よりさらに好ましくは６，５００ｍＰａ・ｓ以下、よりさらに好ましくは５，０００ｍＰａ・ｓ以下、よりさらに好ましくは２，０００ｍＰａ・ｓ以下、よりさらに好ましくは１，０００ｍＰａ・ｓ以下、よりさらに好ましくは７００ｍＰａ・ｓ以下である。
　皮膚外用剤組成物が低粘度であるほど皮膚への供給量を制御し難くなるが、本発明の皮膚外用剤によれば、低粘度の組成物であっても一定量を吐出して皮膚に供給できる点で有利である。
　組成物を収容する定量吐出容器がストローク式で且つポンプタイプの押圧式容器である場合、該組成物の２５℃における粘度は、吐出性及び塗布時の塗り広げやすさを高める観点から、よりさらに好ましくは１０，０００ｍＰａ・ｓ以下、よりさらに好ましくは８，０００ｍＰａ・ｓ以下、よりさらに好ましくは６，５００ｍＰａ・ｓ以下、よりさらに好ましくは５，０００ｍＰａ・ｓ以下、よりさらに好ましくは２，０００ｍＰａ・ｓ以下、よりさらに好ましくは１，０００ｍＰａ・ｓ以下、よりさらに好ましくは７００ｍＰａ・ｓ以下である。また、吐出時の液だれを防ぐ観点及び塗布時のこぼれにくさの観点から、５．０ｍＰａ・ｓ以上、さらには１００ｍＰａ・ｓ以上であってもよい。
　組成物を収容する定量吐出容器がストローク式で且つスプレータイプの押圧式容器である場合、該組成物の２５℃における粘度は、吐出性及び塗布時の塗り広げやすさを高める観点から、よりさらに好ましくは１，０００ｍＰａ・ｓ以下、よりさらに好ましくは８００ｍＰａ・ｓ以下、よりさらに好ましくは５００ｍＰａ・ｓ以下、よりさらに好ましくは３００ｍＰａ・ｓ以下、よりさらに好ましくは２００ｍＰａ・ｓ以下、よりさらに好ましくは１００ｍＰａ・ｓ以下である。また、吐出時の液だれを防ぐ観点及び塗布時のこぼれにくさの観点から、５．０ｍＰａ・ｓ以上、さらには１０．０ｍＰａ・ｓ以上であってもよい。 (viscosity)
The viscosity of the external preparation composition for skin at 25° C. is preferably 1.0 mPa·s or more from the viewpoint of uniforming the discharge amount per discharge operation of the metered discharge container and from the viewpoint of improving the applicability to the skin. , more preferably 2.0 mPa s or more, and still more preferably 3.0 mPa s or more, from the viewpoint of improving the dischargeability of the metered discharge container and from the viewpoint of improving or maintaining the sterilization or virucidal properties, preferably 30,000 mPa s or less, more preferably 25,000 mPa s or less, still more preferably 10,000 mPa s or less, even more preferably 8,000 mPa s or less, still more preferably 6,500 mPa s or less, and more It is more preferably 5,000 mPa·s or less, still 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.
The lower the viscosity of the external skin preparation composition, the more difficult it is to control the amount supplied to the skin. It is advantageous in that it can be supplied.
When the metered discharge container containing the composition is a stroke-type and pump-type pressing container, the viscosity of the composition at 25° C. is further increased from the viewpoint of enhancing dischargeability and spreadability during application. Preferably 10,000 mPa·s or less, more preferably 8,000 mPa·s or less, still more preferably 6,500 mPa·s or less, still more preferably 5,000 mPa·s or less, still more preferably 2,000 mPa·s s or less, more preferably 1,000 mPa·s or less, and even more preferably 700 mPa·s or less. In addition, from the viewpoint of preventing dripping during discharge and preventing spillage during coating, the viscosity may be 5.0 mPa·s or more, further 100 mPa·s or more.
When the metered discharge container containing the composition is a stroke-type and spray-type push-type container, the viscosity of the composition at 25° C. is further increased from the viewpoint of enhancing dischargeability and ease of spreading during application. Preferably 1,000 mPa s or less, still more preferably 800 mPa s or less, still more preferably 500 mPa s or less, still more preferably 300 mPa s or less, still more preferably 200 mPa s or less, still more preferably 100 mPa・It is less than or equal to s. In addition, from the viewpoint of preventing dripping during discharge and preventing spillage during coating, the viscosity may be 5.0 mPa·s or more, further 10.0 mPa·s or more.
　組成物を収容する定量吐出容器がスクイーズ式の押圧式容器である場合、該組成物の２５℃における粘度は、定量吐出性の観点から、よりさらに好ましくは２５，０００ｍＰａ・ｓ以下、よりさらに好ましくは１０，０００ｍＰａ・ｓ以下、よりさらに好ましくは８，０００ｍＰａ・ｓ以下、よりさらに好ましくは６，５００ｍＰａ・ｓ以下、よりさらに好ましくは２，０００ｍＰａ・ｓ以下であり、同様の観点から、よりさらに好ましくは１００ｍＰａ・ｓ以上、よりさらに好ましくは５００ｍＰａ・ｓ以上である。
　組成物を収容する定量吐出容器が電動ディスペンサー式容器である場合、該組成物の２５℃における粘度は、吐出性の観点から、よりさらに好ましくは１，０００ｍＰａ・ｓ以下、よりさらに好ましくは８００ｍＰａ・ｓ以下、よりさらに好ましくは５００ｍＰａ・ｓ以下、よりさらに好ましくは３００ｍＰａ・ｓ以下、よりさらに好ましくは２００ｍＰａ・ｓ以下、よりさらに好ましくは１００ｍＰａ・ｓ以下である。また、吐出時の液だれを防ぐ観点及び塗布時のこぼれにくさの観点から、５．０ｍＰａ・ｓ以上、さらには１０．０ｍＰａ・ｓ以上であってもよい。
　組成物の２５℃における粘度は、具体的には実施例に記載の方法により測定できる。 When the metered discharge container containing the composition is a squeeze-type pressure container, the viscosity of the composition at 25° C. is more preferably 25,000 mPa·s or less, still more preferably 25,000 mPa·s or less, from the viewpoint of metered discharge performance. is 10,000 mPa s or less, more preferably 8,000 mPa s or less, even more preferably 6,500 mPa s or less, and even more preferably 2,000 mPa s or less. It is preferably 100 mPa·s or more, and more preferably 500 mPa·s or more.
When the fixed-quantity discharge container containing the composition is an electric dispenser container, the viscosity of the composition at 25° C. is more preferably 1,000 mPa·s or less, still more preferably 800 mPa·s or less, from the viewpoint of dischargeability. s or less, more preferably 500 mPa·s or less, still more preferably 300 mPa·s or less, even more preferably 200 mPa·s or less, and even more preferably 100 mPa·s or less. In addition, from the viewpoint of preventing dripping during discharge and preventing spillage during coating, the viscosity may be 5.0 mPa·s or more, further 10.0 mPa·s or more.
Specifically, the viscosity of the composition at 25° C. can be measured by the method described in Examples.
（ｐＨ）
　皮膚外用剤組成物は、本発明における組成物中の成分（Ａ１）の含有割合を調整する観点、及び、皮膚刺激性を抑制する観点から、２５℃におけるｐＨが、好ましくは３．５以上、より好ましくは３．７以上である。また、殺菌又は殺ウイルス性向上の観点から、好ましくは５．０以下、より好ましくは４．５以下である。そして、皮膚外用剤組成物の２５℃におけるｐＨは、好ましくは３．５以上５．０以下、より好ましくは３．５以上４．５以下、さらに好ましくは３．７以上４．５以下である。
　組成物の２５℃におけるｐＨは、具体的には実施例に記載の方法により測定できる。 (pH)
The skin external preparation composition preferably has a pH at 25°C of 3.5 or more, from the viewpoint of adjusting the content ratio of the component (A1) in the composition of the present invention and from the viewpoint of suppressing skin irritation. More preferably, it is 3.7 or more. From the viewpoint of improving bactericidal or virucidal properties, it is preferably 5.0 or less, more preferably 4.5 or less. The pH of the external skin preparation composition at 25°C is preferably 3.5 or more and 5.0 or less, more preferably 3.5 or more and 4.5 or less, and still more preferably 3.7 or more and 4.5 or less. .
Specifically, the pH of the composition at 25°C can be measured by the method described in Examples.
＜皮膚外用剤組成物の形態＞
　本発明に用いる皮膚外用剤組成物は、２５℃において流動性を有するものであればよい。形態は特に制限されず、例えば、液状、ジェル状、クリーム状、泡状とすることができる。皮膚へ塗り広げやすく、意図する塗布面においてムラなく殺菌又は殺ウイルス成分を発揮させる観点からは、液状であることが好ましい。また、皮膚に適用した際、皮膚からの垂れ落ちを防ぎ、意図どおりの量で成分（Ａ１）を皮膚へ供給する観点からは、ジェル状、クリーム状、泡状であることが好ましい。
　さらに、組成物は乳化組成物の形態であってもよく、該乳化組成物としては水中油型乳化組成物、油中水型乳化組成物のいずれでもよい。皮膚へ塗り広げやすく、意図する塗布面においてムラなく殺菌又は殺ウイルス成分を発揮させる観点からは、水中油型乳化組成物であることが好ましい。また、皮膚に適用した際、皮膚からの垂れ落ちを防ぎ、意図どおりの量で成分（Ａ１）を供給する観点からは、油中水型乳化組成物であることが好ましい。 <Form of topical composition for skin>
The external skin preparation composition used in the present invention may have fluidity at 25°C. The form is not particularly limited, and may be, for example, liquid, gel, cream, or foam. It is preferably in a liquid form, from the viewpoint of being easy to spread on the skin and exhibiting the bactericidal or virucidal component evenly on the intended application surface. In addition, from the viewpoint of preventing dripping from the skin when applied to the skin and supplying the intended amount of the component (A1) to the skin, it is preferably gel-like, cream-like, or foam-like.
Furthermore, the composition may be in the form of an emulsion composition, and the emulsion composition may be either an oil-in-water emulsion composition or a water-in-oil emulsion composition. An oil-in-water emulsified composition is preferred from the viewpoint of easy application to the skin and the ability to exhibit the bactericidal or virucidal component evenly on the intended application surface. In addition, from the viewpoint of preventing dripping from the skin when applied to the skin and supplying the component (A1) in the intended amount, it is preferably a water-in-oil emulsion composition.
　本発明の皮膚外用剤は、下記（I）又は（II）の態様であることがより好ましい。
（I）皮膚外用剤組成物が定量吐出容器に収容されてなる皮膚外用剤であって、
　前記組成物は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を含有し、
　該組成物中に存在する前記酸のうち、酸型で存在するものを成分（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の前記成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である皮膚外用剤において、
　前記成分（Ａ）が乳酸又はその塩であり、
　前記組成物中の、前記成分（Ａ）に対する、前記成分（Ａ）以外の有機酸又はその塩（Ｃ）の質量比［（Ｃ）／（Ａ）］が１未満であり、
　前記組成物の２５℃におけるｐＨが３．５以上５．０以下である、皮膚外用剤。
（II）皮膚外用剤組成物が定量吐出容器に収容されてなる皮膚外用剤であって、
　前記組成物は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を含有し、
　該組成物中に存在する前記酸のうち、酸型で存在するものを成分（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の前記成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である皮膚外用剤において、
　前記組成物が、さらにノニオン性増粘剤（Ｂ）を含有し、
　前記組成物の２５℃における粘度が、１００ｍＰａ・ｓ以上１０，０００ｍＰａ・ｓ以下である、皮膚外用剤。 The external preparation for skin of the present invention is more preferably in the following (I) or (II) mode.
(I) An external skin preparation comprising an external skin preparation composition contained in a metered discharge container,
The composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid,
Among the acids present in the composition, when an acid present in an acid form is defined as the component (A1), the component (A1 ) content of 0.05 mg or more and 80 mg or less,
The component (A) is lactic acid or a salt thereof,
The mass ratio [(C)/(A)] of the organic acid other than the component (A) or a salt thereof (C) to the component (A) in the composition is less than 1;
An external preparation for skin, wherein the composition has a pH of 3.5 or more and 5.0 or less at 25°C.
(II) An external skin preparation comprising an external skin preparation composition contained in a metered discharge container,
The composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid,
Among the acids present in the composition, when an acid present in an acid form is defined as the component (A1), the component (A1 ) content of 0.05 mg or more and 80 mg or less,
The composition further contains a nonionic thickener (B),
An external preparation for skin, wherein the composition has a viscosity of 100 mPa·s or more and 10,000 mPa·s or less at 25°C.
　前記（I）の態様の皮膚外用剤は、上記構成を有することにより、顕著な殺菌又は殺ウイルス性向上効果を奏する。
　前記（I）の態様の皮膚外用剤に用いる皮膚外用剤組成物中の、成分（Ａ）に対する、成分（Ａ）以外の有機酸又はその塩（Ｃ）の質量比［（Ｃ）／（Ａ）］は、１未満であり、好ましくは０．８以下、より好ましくは０．６以下、さらに好ましくは０．５以下、よりさらに好ましくは０．３以下、よりさらに好ましくは０．２以下、よりさらに好ましくは０．１以下、よりさらに好ましくは０．０５以下、よりさらに好ましくは０．０１以下であり、よりさらに好ましくは実質０である。
　前記（I）の態様の皮膚外用剤に用いる皮膚外用剤組成物の２５℃におけるｐＨは、３．５以上５．０以下であり、好ましくは３．５以上４．５以下、より好ましくは３．７以上４．５以下である。
　その他の要件並びにその好適範囲については、前記と同じである。 The external preparation for skin according to the aspect (I) exhibits a remarkable effect of improving bactericidal or virucidal properties by having the above constitution.
The mass ratio of the organic acid or its salt (C) other than the component (A) to the component (A) in the external skin preparation composition used for the external skin preparation of the aspect (I) [(C)/(A )] is less than 1, preferably 0.8 or less, more preferably 0.6 or less, even more preferably 0.5 or less, even more preferably 0.3 or less, even more preferably 0.2 or less, It is even more preferably 0.1 or less, still more preferably 0.05 or less, still more preferably 0.01 or less, and even more preferably substantially zero.
The pH at 25° C. of the external skin preparation composition used in the external skin preparation of the aspect (I) is 3.5 or more and 5.0 or less, preferably 3.5 or more and 4.5 or less, more preferably 3. .7 or more and 4.5 or less.
Other requirements and preferred ranges are the same as above.
　前記（II）の態様の皮膚外用剤は、上記構成を有することにより、殺菌又は殺ウイルス性と、より良好な使用感とを両立することができる。
　前記（II）の態様の皮膚外用剤に用いる皮膚外用剤組成物の２５℃における粘度は、殺菌又は殺ウイルス性を維持する観点、及び使用感向上の観点から、１００ｍＰａ・ｓ以上、１０，０００ｍＰａ・ｓ以下であり、好ましくは１００ｍＰａ・ｓ以上５，０００ｍＰａ・ｓ以下であり、より好ましくは１００ｍＰａ・ｓ以上８，０００ｍＰａ・ｓ以下であり、さらに好ましくは１００ｍＰａ・ｓ以上２，０００ｍＰａ・ｓ以下であり、よりさらに好ましくは１００ｍＰａ・ｓ以上、１，０００ｍＰａ・ｓ以下であり、よりさらに好ましくは１００ｍＰａ・ｓ以上８００ｍＰａ・ｓ以下、よりさらに好ましくは１００ｍＰａ・ｓ以上７００ｍＰａ・ｓ以下である。
　その他の要件並びにその好適範囲については、前記と同じである。 The external preparation for skin according to the aspect (II) can achieve both bactericidal or virucidal properties and a better feel during use by having the above constitution.
The viscosity at 25° C. of the external skin preparation composition used in the external skin preparation of the aspect (II) is 100 mPa·s or more and 10,000 mPa from the viewpoint of maintaining the bactericidal or virucidal properties and improving the feeling of use. s or less, preferably 100 mPa s or more and 5,000 mPa s or less, more preferably 100 mPa s or more and 8,000 mPa s or less, still more preferably 100 mPa s or more and 2,000 mPa s or less more preferably 100 mPa·s or more and 1,000 mPa·s or less, still more preferably 100 mPa·s or more and 800 mPa·s or less, still more preferably 100 mPa·s or more and 700 mPa·s or less.
Other requirements and preferred ranges are the same as above.
＜皮膚外用剤の形態＞
　本発明の皮膚外用剤は、吐出した組成物中に含まれる、殺菌又は殺ウイルス成分である成分（Ａ）を皮膚表面に残留させることで、皮膚表面において殺菌又は殺ウイルス性を発揮する。該効果を得る観点から、本発明の皮膚外用剤はリーブオン皮膚外用剤であることが好ましい。すなわち本発明の皮膚外用剤を使用する際には、定量吐出容器より吐出した組成物を皮膚に塗布等により適用した後に該組成物を水洗等で除去せず、皮膚表面に残留させて使用する。
　菌又はウイルスによる接触感染を防ぐという観点からは、本発明の皮膚外用剤は、手指用のリーブオン皮膚外用剤であることがより好ましい。 <Form of external preparation for skin>
The external preparation for skin of the present invention exhibits bactericidal or virucidal properties on the skin surface by leaving component (A), which is a bactericidal or virucidal component, contained in the discharged composition on the skin surface. From the viewpoint of obtaining the effect, the external skin preparation of the present invention is preferably a leave-on skin preparation. That is, when the external skin preparation of the present invention is used, the composition discharged from a metered discharge container is applied to the skin by coating or the like, and then the composition is not removed by washing with water or the like, but left on the skin surface before use. .
From the viewpoint of preventing contact infection with bacteria or viruses, the external skin preparation of the present invention is more preferably a leave-on skin preparation for fingers.
＜殺菌又は殺ウイルス性を発現する対象となる菌又はウイルス＞
　本発明の皮膚外用剤が殺菌又は殺ウイルス性を発現する対象となる菌又はウイルスとしては、酸との接触により不活性化又は死滅するものであれば特に制限されず、例えば厚生労働省の保育所における感染症対策ガイドラインに記載の微生物を適用することができると考えられる。
　具体的には、菌としてはグラム陽性細菌である炭疽菌、結核菌、溶血性レンサ球菌、黄色ブドウ球菌、肺炎球菌等、あるいはグラム陰性細菌である野兎病菌、ペスト菌、ブルセラ菌、鼻疽菌、コレラ菌、サルモネラ菌、赤痢菌、腸管出血性大腸菌、百日咳菌等が挙げられる。また、ウイルスとしては、エンベロープウイルスであるアレナウイルス、エボラウイルス、痘そうウイルス、ナイロウイルス、マールブルグウイルス、コロナウイルス、サル痘ウイルス、ベータコロナウイルス、インフルエンザウイルス、ＲＳウイルス、ヘルペスウイルス、ムンプスウイルス、水痘・帯状疱疹ウイルス、風しんウイルス、麻しんウイルス等、及びノンエンベロープウイルスであるエンテロウイルス、アデノウイルス、コクサッキーウイルス、ノロウイルス、ロタウイルス等が挙げられる。
　なお、本実施例では、セラチア菌を例に挙げて殺菌及び殺ウイルス性を評価しているが、本発明が対象とする菌又はウイルスはこれに限定されない。 <Bacterium or virus to be targeted for bactericidal or virucidal activity>
Bacteria or viruses for which the external preparation for skin of the present invention exhibits bactericidal or virucidal properties are not particularly limited as long as they are inactivated or killed by contact with acid. It is thought that the microorganisms described in the guidelines for infectious disease control in Japan can be applied.
Specifically, the bacteria include Gram-positive bacteria such as Bacillus anthracis, Mycobacterium tuberculosis, Streptococcus hemolyticus, Staphylococcus aureus, and Streptococcus pneumoniae, or Gram-negative bacteria such as Tularemia, Yersinia pestis, Brucella, and Bacillus mallei. , cholera, salmonella, shigella, enterohemorrhagic Escherichia coli, and pertussis. Viruses include envelope viruses such as arenavirus, ebola virus, smallpox virus, nairovirus, marburg virus, coronavirus, monkeypox virus, beta coronavirus, influenza virus, respiratory syncytial virus, herpes virus, mumps virus, and varicella virus.・Herpes zoster virus, rubella virus, measles virus, etc., and non-enveloped viruses such as enterovirus, adenovirus, coxsackievirus, norovirus, rotavirus, etc.
In this example, bactericidal and virucidal properties were evaluated using Serratia as an example, but the target bacteria or viruses of the present invention are not limited thereto.
［成分（Ａ）を皮膚表面の適用部位に供給する方法］
　本発明はまた、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を皮膚表面の適用部位に供給する方法であって、下記工程（Ｉ）及び工程（ＩＩ）を順に有する方法（以下、単に「本発明の方法」ともいう）を提供する。
工程（Ｉ）：前記適用部位を洗浄する工程
工程（ＩＩ）：前記成分（Ａ）を含有する組成物が収容された定量吐出容器から該組成物を１回の吐出操作により吐出して前記適用部位に供給する工程であって、該組成物中に存在する前記酸のうち、酸型で存在するものを（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である、工程 [Method of supplying component (A) to application site on skin surface]
The present invention also provides a method for supplying one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid to an application site on the skin surface, comprising the following steps (I) and A method having (II) in order (hereinafter also simply referred to as "the method of the present invention") is provided.
Step (I): The step of washing the application site Step (II): The composition containing the component (A) is discharged from a metered discharge container containing the composition by one discharge operation, and the application is performed. In the step of supplying to the site, among the acids present in the composition, when the acid existing in the acid form is (A1), it is discharged from the fixed amount discharge container by one discharge operation. A step in which the content of component (A1) in the composition is 0.05 mg or more and 80 mg or less
　本発明の方法によれば、皮膚表面において優れた殺菌又は殺ウイルス性を発揮し、且つ、皮膚刺激性を抑制することができる。成分（Ａ）、該成分（Ａ）を含有する組成物、定量吐出容器、及びこれらの好適態様については前記と同じである。 According to the method of the present invention, excellent bactericidal or virucidal properties can be exhibited on the skin surface, and skin irritation can be suppressed. The component (A), the composition containing the component (A), the metered discharge container, and preferred embodiments thereof are the same as described above.
　工程（Ｉ）においては、予め水、石鹸、ボディソープ、ハンドソープ等を用いて、皮膚表面の適用部位を洗浄する。洗浄後の皮膚は、生来存在する乳酸等の成分が洗い流され、外界に存在する菌やウイルスの防御力が低下している状態であることから、工程（Ｉ）を行った後に工程（ＩＩ）で前記組成物を適用し、本発明の方法を実施することが好ましい。 In step (I), water, soap, body soap, hand soap, etc. are used in advance to wash the application site on the skin surface. After washing, the skin is in a state where naturally occurring components such as lactic acid are washed away, and the defense against external bacteria and viruses is reduced. Therefore, step (II) is performed after step (I). It is preferred to apply the composition and carry out the method of the invention in.
　工程（Ｉ）で洗浄を行った後、皮膚表面の適用部位は風乾等により乾燥させてから工程（ＩＩ）を行うことができる。 After washing in step (I), the application site on the skin surface can be dried by air drying or the like before step (II) can be performed.
　工程（ＩＩ）では、工程（Ｉ）において洗浄した皮膚表面の適用部位に、前記成分（Ａ）を含有する組成物を吐出する。定量吐出容器から１回の吐出操作により吐出される組成物中の成分（Ａ１）の含有量は、殺菌又は殺ウイルス性向上の観点から、０．０５ｍｇ以上であり、好ましくは０．１ｍｇ以上、より好ましくは０．２ｍｇ以上、さらに好ましくは０．４ｍｇ以上、よりさらに好ましくは０．５ｍｇ以上、よりさらに好ましくは１．０ｍｇ以上、よりさらに好ましくは２．０ｍｇ以上であり、皮膚刺激性を抑制する観点から、８０ｍｇ以下であり、好ましくは６０ｍｇ以下、より好ましくは５０ｍｇ以下、さらに好ましくは４５ｍｇ以下である。そして、定量吐出容器から１回の吐出操作により吐出される組成物中の成分（Ａ１）の含有量は、０．０５ｍｇ以上８０ｍｇ以下であり、好ましくは０．１ｍｇ以上６０ｍｇ以下、より好ましくは０．２ｍｇ以上６０ｍｇ以下、さらに好ましくは０．４ｍｇ以上５０ｍｇ以下、よりさらに好ましくは０．５ｍｇ以上５０ｍｇ以下、よりさらに好ましくは１．０ｍｇ以上４５ｍｇ以下、よりさらに好ましくは２．０ｍｇ以上４５ｍｇ以下である。
　１回の吐出操作により吐出される組成物中の成分（Ａ１）の含有量は、前記と同様の方法で求めることができる。 In step (II), the composition containing component (A) is discharged onto the application site on the skin surface that has been washed in step (I). The content of the component (A1) in the composition discharged from the metered discharge container by one discharge operation is 0.05 mg or more, preferably 0.1 mg or more, from the viewpoint of improving sterilization or virucidal properties. More preferably 0.2 mg or more, still more preferably 0.4 mg or more, still more preferably 0.5 mg or more, still more preferably 1.0 mg or more, still more preferably 2.0 mg or more, suppressing skin irritation 80 mg or less, preferably 60 mg or less, more preferably 50 mg or less, and even more preferably 45 mg or less, from the viewpoint of The content of component (A1) in the composition discharged from the metered discharge container by one discharge operation is 0.05 mg or more and 80 mg or less, preferably 0.1 mg or more and 60 mg or less, more preferably 0 mg. 2 mg or more and 60 mg or less, more preferably 0.4 mg or more and 50 mg or less, even more preferably 0.5 mg or more and 50 mg or less, even more preferably 1.0 mg or more and 45 mg or less, still more preferably 2.0 mg or more and 45 mg or less .
The content of component (A1) in the composition ejected by one ejection operation can be obtained by the same method as described above.
　工程（ＩＩ）で前記組成物を皮膚に供給した後は、水洗等で該組成物を除去せず、皮膚表面に残留させることが好ましい。該組成物をリーブオン製剤として用いて、殺菌又は殺ウイルス成分である成分（Ａ）を皮膚表面に残留させることにより、皮膚表面に殺菌又は殺ウイルス性を付与できるためである。 After supplying the composition to the skin in step (II), it is preferable to leave the composition on the skin surface without removing it by washing with water or the like. This is because the composition can be used as a leave-on preparation to leave the component (A), which is a bactericidal or virucidal component, on the skin surface, thereby imparting bactericidal or virucidal properties to the skin surface.
　上述した実施形態に関し、本発明はさらに以下を開示する。
＜１＞
　皮膚外用剤組成物が定量吐出容器に収容されてなる皮膚外用剤であって、
　前記組成物は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を含有し、
　該組成物中に存在する前記酸のうち、酸型で存在するものを成分（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である、皮膚外用剤。
＜２＞
　前記定量吐出容器から１回の吐出操作により吐出される前記組成物中の成分（Ａ１）の含有量が、好ましくは０．１ｍｇ以上６０ｍｇ以下、より好ましくは０．２ｍｇ以上６０ｍｇ以下、さらに好ましくは０．４ｍｇ以上５０ｍｇ以下、よりさらに好ましくは０．５ｍｇ以上５０ｍｇ以下、よりさらに好ましくは１．０ｍｇ以上４５ｍｇ以下、よりさらに好ましくは２．０ｍｇ以上４５ｍｇ以下である、＜１＞に記載の皮膚外用剤。
＜３＞
　前記定量吐出容器から１回の吐出操作により吐出される前記組成物の量が、好ましくは０．０５ｇ以上３．０ｇ以下、より好ましくは０．１ｇ以上２．５ｇ以下、さらに好ましくは０．２ｇ以上２．０ｇ以下である、＜１＞又は＜２＞に記載の皮膚外用剤。
＜４＞
　前記成分（Ａ）が乳酸又はその塩、好ましくは乳酸、乳酸カリウム、乳酸ナトリウム、及び乳酸カルシウムからなる群から選ばれる１種以上、より好ましくは乳酸を含む、＜１＞～＜３＞のいずれか１に記載の皮膚外用剤。
＜５＞
　前記成分（Ａ）が乳酸を含み、成分（Ａ）全量中における乳酸又はその塩の含有量が、好ましくは８０質量％以上であり、より好ましくは９０質量％以上であり、最も好ましくは１００質量％である、＜１＞～＜４＞のいずれか１に記載の皮膚外用剤。
＜６＞
　前記組成物中の成分（Ａ）の含有量が、好ましくは０．０５質量％以上１５質量％以下、より好ましくは０．０５質量％以上１０質量％以下、さらに好ましくは０．１質量％以上１０質量％以下、さらに好ましくは０．２質量％以上５．０質量％以下、よりさらに好ましくは０．３質量％以上４．０質量％以下、よりさらに好ましくは０．５質量％以上３．０質量％以下、よりさらに好ましくは０．５質量％以上２．５質量％以下、よりさらに好ましくは０．５質量％以上２．０質量％以下である、＜１＞～＜５＞のいずれか１に記載の皮膚外用剤。
＜７＞
　前記組成物中の成分（Ａ１）の含有量が、好ましくは０．０２質量％以上１０質量％以下、より好ましくは０．０４質量％以上５．０質量％以下、さらに好ましくは０．０５質量％以上４．０質量％以下、よりさらに好ましくは０．１質量％以上３．０質量％以下、よりさらに好ましくは０．２質量％以上２．５質量％以下、よりさらに好ましくは０．３質量％以上２．０質量％以下、よりさらに好ましくは０．３質量％以上１．０質量％以下である、＜１＞～＜６＞のいずれか１に記載の皮膚外用剤。
＜８＞
　前記組成物中に存在する前記成分（Ａ）に由来する酸のうち、酸型で存在するものを成分（Ａ１）、解離型で存在するものを成分（Ａ２）とした場合に、前記組成物中のモル比［（Ａ１）／｛（Ａ１）＋（Ａ２）｝］が、好ましくは０．２以上０．６以下、より好ましくは０．３以上０．５５以下、さらに好ましくは０．４以上０．５以下である、＜１＞～＜７＞のいずれか１に記載の皮膚外用剤。
＜９＞
　前記組成物がさらに成分（Ｂ）としてノニオン性増粘剤を含有する、＜１＞～＜８＞のいずれか１に記載の皮膚外用剤。
＜１０＞
　前記成分（Ｂ）が水溶性のノニオン性増粘剤、好ましくはセルロースエーテル類、プロピレングリコールアルギネート、ポリビニルアルコール、ポリビニルピロリドン、ヒドロキシプロピルグアーガム、ローカストビーンガム、アミロース、ヒドロキシエチルアミロース、澱粉又はその誘導体からなる群から選ばれる１種又は２種以上、より好ましくはセルロースエーテル類及びポリビニルアルコールからなる群から選ばれる１種以上であり、さらに好ましくはヒドロキシブチルメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ヒドロキシエチルセルロース、及びポリビニルアルコールからなる群から選ばれる１種以上、よりさらに好ましくはヒドロキシエチルセルロース及びポリビニルアルコールからなる群から選ばれる１種以上、よりさらに好ましくはヒドロキシエチルセルロースである、＜９＞に記載の皮膚外用剤。
＜１１＞
　前記ポリビニルアルコールの重合度が、好ましくは５００以上８，０００以下、より好ましくは７００以上８，０００以下、さらに好ましくは１，０００以上６，０００以下、よりさらに好ましくは１，５００以上６，０００以下、よりさらに好ましくは２，０００以上５，０００以下である、＜１０＞に記載の皮膚外用剤。
＜１２＞
　前記ポリビニルアルコールのケン価度が、好ましくは８０モル％以上、より好ましくは８５モル％以上、さらに好ましくは９０モル％以上、よりさらに好ましくは９５モル％以上であり、１００モル％以下である、＜１０＞又は＜１１＞に記載の皮膚外用剤。
＜１３＞
　前記組成物中の成分（Ｂ）の含有量が、好ましくは０．０１質量％以上２０質量％以下、より好ましくは０．０２質量％以上１５質量％以下、さらに好ましくは０．０５質量％以上１５質量％以下、よりさらに好ましくは０．１質量％以上１０質量％以下、よりさらに好ましくは０．２質量％以上５質量％以下、よりさらに好ましくは０．２質量％以上３質量％以下、よりさらに好ましくは０．２質量％以上１質量％以下、よりさらに好ましくは０．２質量％以上０．５質量％以下である、＜９＞～＜１２＞のいずれか１に記載の皮膚外用剤。
＜１４＞
　前記組成物がさらに水を含有し、該組成物中の水の含有量が、好ましくは４０質量％以上、より好ましくは７０質量％以上、さらに好ましくは８０質量％以上、よりさらに好ましくは８５質量％以上、よりさらに好ましくは９０質量％以上、よりさらに好ましくは９５質量％以上であり、また、好ましくは９９．９５質量％以下である、＜１＞～＜１３＞のいずれか１に記載の皮膚外用剤。
＜１５＞
　前記組成物中の成分（Ａ）及び水の合計含有量が、好ましくは７０．０５質量％以上、より好ましくは７５質量％以上、さらに好ましくは８０質量％以上、よりさらに好ましくは８５質量％以上、よりさらに好ましくは９０質量％以上、よりさらに好ましくは９５質量％以上であり、また、１００質量％以下である、＜１＞～＜１４＞のいずれか１に記載の皮膚外用剤。 The present invention further discloses the following regarding the above-described embodiments.
<1>
An external skin preparation comprising an external skin preparation composition contained in a fixed-quantity discharge container,
The composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid,
Among the acids present in the composition, when an acid present in an acid form is used as the component (A1), the component (A1) in the composition discharged from the metered discharge container by one discharge operation content of 0.05 mg or more and 80 mg or less.
<2>
The content of the component (A1) in the composition discharged from the fixed quantity discharge container by one discharge operation is preferably 0.1 mg or more and 60 mg or less, more preferably 0.2 mg or more and 60 mg or less, still more preferably 0.4 mg or more and 50 mg or less, still more preferably 0.5 mg or more and 50 mg or less, still more preferably 1.0 mg or more and 45 mg or less, still more preferably 2.0 mg or more and 45 mg or less, for external use on the skin according to <1> agent.
<3>
The amount of the composition discharged from the fixed quantity discharge container in one discharge operation is preferably 0.05 g or more and 3.0 g or less, more preferably 0.1 g or more and 2.5 g or less, and still more preferably 0.2 g. The external preparation for skin according to <1> or <2>, which is 2.0 g or less.
<4>
Any of <1> to <3>, wherein the component (A) contains lactic acid or a salt thereof, preferably one or more selected from the group consisting of lactic acid, potassium lactate, sodium lactate, and calcium lactate, more preferably lactic acid. 1. The skin external preparation according to 1.
<5>
The component (A) contains lactic acid, and the content of lactic acid or a salt thereof in the total amount of component (A) is preferably 80% by mass or more, more preferably 90% by mass or more, and most preferably 100% by mass. %, the skin external preparation according to any one of <1> to <4>.
<6>
The content of component (A) in the composition is preferably 0.05% by mass or more and 15% 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 or more. 10 mass % or less, more preferably 0.2 mass % or more and 5.0 mass % or less, even more preferably 0.3 mass % or more and 4.0 mass % or less, still more preferably 0.5 mass % or more3. Any of <1> to <5>, which is 0% by mass or less, more preferably 0.5% by mass or more and 2.5% by mass or less, and still more preferably 0.5% by mass or more and 2.0% by mass or less 1. The skin external preparation according to 1.
<7>
The content of component (A1) in the composition is preferably 0.02% by mass or more and 10% by mass or less, more preferably 0.04% by mass or more and 5.0% by mass or less, and still more preferably 0.05% by mass. % or more and 4.0 mass % or less, more preferably 0.1 mass % or more and 3.0 mass % or less, still more preferably 0.2 mass % or more and 2.5 mass % or less, still more preferably 0.3 mass % The external preparation for skin according to any one of <1> to <6>, which is 0.3% to 1.0% by mass, more preferably 0.3% to 1.0% by mass.
<8>
Among the acids derived from the component (A) present in the composition, when the component (A1) exists in an acid form and the component (A2) exists in a dissociated form, the composition is preferably 0.2 or more and 0.6 or less, more preferably 0.3 or more and 0.55 or less, still more preferably 0.4 The external preparation for skin according to any one of <1> to <7>, which is 0.5 or less.
<9>
The external preparation for skin according to any one of <1> to <8>, wherein the composition further contains a nonionic thickener as component (B).
<10>
The component (B) is a water-soluble nonionic thickener, preferably cellulose ethers, propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropyl guar gum, locust bean gum, amylose, hydroxyethyl amylose, starch or derivatives thereof. One or more selected from the group consisting of, more preferably one or more selected from the group consisting of cellulose ethers and polyvinyl alcohols, more preferably hydroxybutylmethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose , and one or more selected from the group consisting of polyvinyl alcohol, more preferably one or more selected from the group consisting of hydroxyethyl cellulose and polyvinyl alcohol, and still more preferably hydroxyethyl cellulose. agent.
<11>
The degree of polymerization of the polyvinyl alcohol is preferably 500 or more and 8,000 or less, more preferably 700 or more and 8,000 or less, still more preferably 1,000 or more and 6,000 or less, still more preferably 1,500 or more and 6,000. The skin external preparation according to <10>, more preferably 2,000 or more and 5,000 or less.
<12>
The saponification degree of the polyvinyl alcohol is preferably 80 mol% or more, more preferably 85 mol% or more, still more preferably 90 mol% or more, still more preferably 95 mol% or more, and 100 mol% or less. The skin external preparation according to <10> or <11>.
<13>
The content of component (B) in the composition is preferably 0.01% by mass or more and 20% by mass or less, more preferably 0.02% by mass or more and 15% by mass or less, and still more preferably 0.05% by mass or more. 15% by mass or less, more preferably 0.1% by mass or more and 10% by mass or less, even more preferably 0.2% by mass or more and 5% by mass or less, still more preferably 0.2% by mass or more and 3% by mass or less, The skin external use according to any one of <9> to <12>, which is more preferably 0.2% by mass or more and 1% by mass or less, and still more preferably 0.2% by mass or more and 0.5% by mass or less. agent.
<14>
The composition further contains water, and the water content in the composition is preferably 40% by mass or more, more preferably 70% by mass or more, still more preferably 80% by mass or more, and even more preferably 85% by mass. % or more, more preferably 90% by mass or more, still more preferably 95% by mass or more, and preferably 99.95% by mass or less, any one of <1> to <13> Skin external agent.
<15>
The total content of component (A) and water in the composition is preferably 70.05% by mass or more, more preferably 75% by mass or more, still more preferably 80% by mass or more, and even more preferably 85% by mass or more. , Still more preferably 90% by mass or more, still more preferably 95% by mass or more, and 100% by mass or less, any one of <1> to <14>.
＜１６＞
　前記組成物がさらにポリオールを含有する、＜１＞～＜１５＞のいずれか１に記載の皮膚外用剤。
＜１７＞
　前記ポリオールが、オクタノール／水分配係数であるｌｏｇＰｏｗ値が－２．０以上を満たす、＜１６＞に記載の皮膚外用剤。
＜１８＞
　前記ポリオールが、プロピレングリコール（１，２－プロパンジオール）、１，３－プロパンジオール、ジプロピレングリコール、１，２－ブチレングリコール、１，３－ブチレングリコール、１，４－ブチレングリコール、２，３－ブタンジオール、１，２－ペンタンジオール、１，５－ペンタンジオール、１，２－ヘキサンジオール、２，５－ヘキサンジオール、１，６－ヘキサンジオール、１，２－ヘプタンジオール、１，７－ヘプタンジオール、１，２－オクタンジオール、１，８－オクタンジオール、１，２－ノナンジオール、１，９－ノナンジオール、１，２－デカンジオール、１，１０－デカンジオール、１，２－ドデカンジオール、１，１２－ドデカンジオール、１，２－テトラデカンジオール、１，２－ヘキサデカンジオール、１，１６－ヘキサデカンジオール、グリセリン、１，２，３－ブタントリオール、１，２，４－ブタントリオール、１，２，５－ペンタントリオール、１，２，６－ヘキサントリオール、１，２，７－ヘプタントリオール、１，２，８－オクタントリオール、１，２，９－ノナントリオール、１，２，１０－デカントリオール、２－メチル－１，３－プロパンジオール、２，２－ジメチル－１，３－プロパンジオール、３－メチル－１，３－ブタンジオール、２－メチルペンタン－２，４－ジオール、２－エチル－１，３－ヘキサンジオール、トリプロピレングリコール、２－ブチル－２－エチル－１，３－プロパンジオール、３－（２－エチルヘキシルオキシ）－１，２－プロパンジオール、（ラウリル／ミリスチル）グリコールヒドロキシプロピルエーテル、３，７，１１，１５－テトラメチルヘキサデカン－１，２，３－トリオール、ポリエチレングリコール、ポリグリセリン、及びＰＰＧ－１０ブタンジオールからなる群から選ばれる１種以上である、＜１６＞又は＜１７＞に記載の皮膚外用剤。
＜１９＞
　前記組成物中のポリオールの含有量が、好ましくは０．０５質量％以上５０％質量％以下、より好ましくは０．１質量％以上５０％質量％以下、さらに好ましくは０．５質量％以上３０質量％以下、よりさらに好ましくは１．０質量％以上３０質量％以下、よりさらに好ましくは１．５質量％以上２０質量％以下、よりさらに好ましくは２．０質量％以上２０質量％以下である、＜１６＞～＜１８＞のいずれか１に記載の皮膚外用剤。
＜２０＞
　前記組成物がｐＨ調整剤、好ましくは無機アルカリ剤、より好ましくはアルカリ金属の水酸化物及びアルカリ土類金属の水酸化物からなる群から選ばれる１種以上、さらに好ましくはアルカリ金属の金属水酸化物、よりさらに好ましくは水酸化ナトリウム及び水酸化カリウムからなる群から選ばれる１種以上、よりさらに好ましくは水酸化ナトリウムを含有する、＜１＞～＜１９＞のいずれか１に記載の皮膚外用剤。
＜２１＞
　前記組成物中の金属イオン濃度が、好ましくは０．００２ｍｏｌ／Ｌ以上０．８０ｍｏｌ／Ｌ以下、より好ましくは０．００２ｍｏｌ／Ｌ以上０．５０ｍｏｌ／Ｌ以下、さらに好ましくは０．００５ｍｏｌ／Ｌ以上０．５０ｍｏｌ／Ｌ以下、よりさらに好ましくは０．０１ｍｏｌ／Ｌ以上０．３０ｍｏｌ／Ｌ以下、よりさらに好ましくは０．０２ｍｏｌ／Ｌ以上０．２０ｍｏｌ／Ｌ以下である、＜１＞～＜２０＞のいずれか１に記載の皮膚外用剤。
＜２２＞
　前記組成物中の炭素数４以下のモノアルコールの含有量が、好ましくは６０質量％以下、より好ましくは５０質量％以下、さらに好ましくは４０質量％以下、よりさらに好ましくは３０質量％以下、よりさらに好ましくは１０質量％以下であり、よりさらに好ましくは５．０質量％以下であり、よりさらに好ましくは１．０質量％以下であり、よりさらに好ましくは０．０５質量％以下であり、よりさらに好ましくは０．０１質量％未満であり、最も好ましくは実質０質量％である、＜１＞～＜２１＞のいずれか１に記載の皮膚外用剤。
＜２３＞
　前記組成物中の成分（Ａ）以外の有機酸又はその塩（Ｃ）の含有量が、好ましくは１５質量％以下、より好ましくは１０質量％以下、さらに好ましくは５質量％以下、よりさらに好ましくは３質量％以下、よりさらに好ましくは１質量％以下、よりさらに好ましくは０．５質量％以下、よりさらに好ましくは０．５質量％未満、よりさらに好ましくは０．１質量％未満であり、最も好ましくは実質０質量％である、＜１＞～＜２２＞のいずれか１に記載の皮膚外用剤。
＜２４＞
　前記組成物中の、成分（Ａ）に対する、成分（Ａ）以外の有機酸又はその塩（Ｃ）の質量比［（Ｃ）／（Ａ）］が、好ましくは１未満であり、より好ましくは０．８以下、さらに好ましくは０．６以下、よりさらに好ましくは０．５以下、よりさらに好ましくは０．３以下、よりさらに好ましくは０．２以下、よりさらに好ましくは０．１以下、よりさらに好ましくは０．０５以下、よりさらに好ましくは０．０１以下であり、よりさらに好ましくは実質０である、＜２３＞に記載の皮膚外用剤。
＜２５＞
　前記組成物中の殺菌剤の含有量が、好ましくは１５質量％以下、より好ましくは１０質量％以下、さらに好ましくは５質量％以下、よりさらに好ましくは３質量％以下、よりさらに好ましくは１質量％以下であり、よりさらに好ましくは０．０７質量％以下であり、よりさらに好ましくは０．０５質量％以下であり、よりさらに好ましくは０．０３質量％以下であり、よりさらに好ましくは０．０１質量％未満であり、最も好ましくは実質０質量％である、＜１＞～＜２４＞のいずれか１に記載の皮膚外用剤。
＜２６＞
　前記組成物が殺菌剤を含有し、該組成物中の殺菌剤の含有量が、好ましくは０．０１質量％以上、さらに好ましくは０．０５質量％以上である、＜１＞～＜２５＞のいずれか１に記載の皮膚外用剤。 <16>
The external preparation for skin according to any one of <1> to <15>, wherein the composition further contains a polyol.
<17>
The external preparation for skin according to <16>, wherein the polyol satisfies a logPow value of -2.0 or more, which is an octanol/water partition coefficient.
<18>
The polyol is propylene glycol (1,2-propanediol), 1,3-propanediol, dipropylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,3 -butanediol, 1,2-pentanediol, 1,5-pentanediol, 1,2-hexanediol, 2,5-hexanediol, 1,6-hexanediol, 1,2-heptanediol, 1,7- Heptanediol, 1,2-octanediol, 1,8-octanediol, 1,2-nonanediol, 1,9-nonanediol, 1,2-decanediol, 1,10-decanediol, 1,2-dodecane Diol, 1,12-dodecanediol, 1,2-tetradecanediol, 1,2-hexadecanediol, 1,16-hexadecanediol, glycerin, 1,2,3-butanetriol, 1,2,4-butanetriol, 1,2,5-pentanetriol, 1,2,6-hexanetriol, 1,2,7-heptanetriol, 1,2,8-octanetriol, 1,2,9-nonanetriol, 1,2,10 -decanetriol, 2-methyl-1,3-propanediol, 2,2-dimethyl-1,3-propanediol, 3-methyl-1,3-butanediol, 2-methylpentane-2,4-diol, 2-ethyl-1,3-hexanediol, tripropylene glycol, 2-butyl-2-ethyl-1,3-propanediol, 3-(2-ethylhexyloxy)-1,2-propanediol, (lauryl/myristyl ) one or more selected from the group consisting of glycol hydroxypropyl ether, 3,7,11,15-tetramethylhexadecane-1,2,3-triol, polyethylene glycol, polyglycerin, and PPG-10 butanediol; The skin external preparation according to <16> or <17>.
<19>
The content of the polyol in the composition is preferably 0.05% by mass or more and 50% by mass or less, more preferably 0.1% by mass or more and 50% by mass or less, and still more preferably 0.5% by mass or more and 30% by mass. % by mass or less, more preferably 1.0% by mass or more and 30% by mass or less, even more preferably 1.5% by mass or more and 20% by mass or less, still more preferably 2.0% by mass or more and 20% by mass or less , The skin external preparation according to any one of <16> to <18>.
<20>
The composition is a pH adjuster, preferably an inorganic alkali agent, more preferably one or more selected from the group consisting of alkali metal hydroxides and alkaline earth metal hydroxides, and more preferably alkali metal metal water. The skin according to any one of <1> to <19>, which contains an oxide, more preferably one or more selected from the group consisting of sodium hydroxide and potassium hydroxide, and still more preferably sodium hydroxide. External agents.
<21>
The metal ion concentration in the composition is preferably 0.002 mol/L or more and 0.80 mol/L or less, more preferably 0.002 mol/L or more and 0.50 mol/L or less, and still more preferably 0.005 mol/L or more. 0.50 mol/L or less, more preferably 0.01 mol/L or more and 0.30 mol/L or less, still more preferably 0.02 mol/L or more and 0.20 mol/L or less, <1> to <20> The skin external preparation according to any one of 1.
<22>
The content of monoalcohols having 4 or less carbon atoms in the composition is preferably 60% by mass or less, more preferably 50% by mass or less, even more preferably 40% by mass or less, still more preferably 30% by mass or less, and more More preferably 10% by mass or less, still more preferably 5.0% by mass or less, still more preferably 1.0% by mass or less, still more preferably 0.05% by mass or less, and more The external preparation for skin according to any one of <1> to <21>, which is more preferably less than 0.01% by mass, and most preferably substantially 0% by mass.
<23>
The content of the organic acid or its salt (C) other than the component (A) in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, and even more preferably is 3% by mass or less, even more preferably 1% by mass or less, even more preferably 0.5% by mass or less, even more preferably less than 0.5% by mass, and even more preferably less than 0.1% by mass; The external preparation for skin according to any one of <1> to <22>, which is most preferably substantially 0% by mass.
<24>
The mass ratio [(C)/(A)] of an organic acid other than component (A) or a salt thereof (C) to component (A) in the composition is preferably less than 1, more preferably 0.8 or less, more preferably 0.6 or less, even more preferably 0.5 or less, still more preferably 0.3 or less, still more preferably 0.2 or less, still more preferably 0.1 or less, more The topical skin preparation according to <23>, which is more preferably 0.05 or less, still more preferably 0.01 or less, and even more preferably substantially 0.
<25>
The content of the fungicide in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 3% by mass or less, and even more preferably 1% by mass. % or less, more preferably 0.07 mass % or less, still more preferably 0.05 mass % or less, still more preferably 0.03 mass % or less, and even more preferably 0.05 mass % or less. The external preparation for skin according to any one of <1> to <24>, which is less than 01% by mass, most preferably substantially 0% by mass.
<26>
<1> to <25>, wherein the composition contains a disinfectant, and the content of the disinfectant in the composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more. The skin external preparation according to any one of 1.
＜２７＞
　前記組成物の２５℃における粘度が、好ましくは１．０ｍＰａ・ｓ以上、より好ましくは２．０ｍＰａ・ｓ以上、さらに好ましくは３．０ｍＰａ・ｓ以上であり、好ましくは３０，０００ｍＰａ・ｓ以下、より好ましくは２５，０００ｍＰａ・ｓ以下、さらに好ましくは１０，０００ｍＰａ・ｓ以下、よりさらに好ましくは８，０００ｍＰａ・ｓ以下、よりさらに好ましくは６，５００ｍＰａ・ｓ以下、よりさらに好ましくは５，０００ｍＰａ・ｓ以下、よりさらに好ましくは２，０００ｍＰａ・ｓ以下、よりさらに好ましくは１，０００ｍＰａ・ｓ以下、よりさらに好ましくは７００ｍＰａ・ｓ以下である、＜１＞～＜２６＞のいずれか１に記載の皮膚外用剤。
＜２８＞
　前記組成物を収容する定量吐出容器がストローク式で且つポンプタイプの押圧式容器であり、該組成物の２５℃における粘度が、よりさらに好ましくは５．０ｍＰａ・ｓ以上、よりさらに好ましくは１００ｍＰａ・ｓ以上である、＜２７＞に記載の皮膚外用剤。
＜２９＞
　前記組成物を収容する定量吐出容器がストローク式で且つスプレータイプの押圧式容器であり、該組成物の２５℃における粘度が、よりさらに好ましくは８００ｍＰａ・ｓ以下、よりさらに好ましくは５００ｍＰａ・ｓ以下、よりさらに好ましくは３００ｍＰａ・ｓ以下、よりさらに好ましくは２００ｍＰａ・ｓ以下、よりさらに好ましくは１００ｍＰａ・ｓ以下であり、よりさらに好ましくは５．０ｍＰａ・ｓ以上、よりさらに好ましくは１０．０ｍＰａ・ｓ以上である、＜２７＞に記載の皮膚外用剤。
＜３０＞
　前記組成物を収容する定量吐出容器がスクイーズ式の押圧式容器であり、該組成物の２５℃における粘度が、よりさらに好ましくは２５，０００ｍＰａ・ｓ以下、よりさらに好ましくは１０，０００ｍＰａ・ｓ以下、よりさらに好ましくは８，０００ｍＰａ・ｓ以下、よりさらに好ましくは６，５００ｍＰａ・ｓ以下、よりさらに好ましくは２，０００ｍＰａ・ｓ以下であり、よりさらに好ましくは１００ｍＰａ・ｓ以上、よりさらに好ましくは５００ｍＰａ・ｓ以上である、＜２７＞に記載の皮膚外用剤。
＜３１＞
　前記組成物を収容する定量吐出容器が電動ディスペンサー式容器であり、該組成物の２５℃における粘度が、よりさらに好ましくは８００ｍＰａ・ｓ以下、よりさらに好ましくは５００ｍＰａ・ｓ以下、よりさらに好ましくは３００ｍＰａ・ｓ以下、よりさらに好ましくは２００ｍＰａ・ｓ以下、よりさらに好ましくは１００ｍＰａ・ｓ以下であり、よりさらに好ましくは５．０ｍＰａ・ｓ以上、よりさらに好ましくは１０．０ｍＰａ・ｓ以上である、＜２７＞に記載の皮膚外用剤。
＜３２＞
　前記組成物の２５℃におけるｐＨが、好ましくは３．５以上５．０以下、より好ましくは３．５以上４．５以下、さらに好ましくは３．７以上４．５以下である、＜１＞～＜３１＞のいずれか１に記載の皮膚外用剤。
＜３３＞
　下記（I）又は（II）の態様である、＜１＞～＜３２＞のいずれか１に記載の皮膚外用剤。
（I）皮膚外用剤組成物が定量吐出容器に収容されてなる皮膚外用剤であって、
　前記組成物は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を含有し、
　該組成物中に存在する前記酸のうち、酸型で存在するものを成分（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の前記成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である皮膚外用剤において、
　前記成分（Ａ）が乳酸又はその塩であり、
　前記組成物中の、前記成分（Ａ）に対する、前記成分（Ａ）以外の有機酸又はその塩（Ｃ）の質量比［（Ｃ）／（Ａ）］が１未満であり、
　前記組成物の２５℃におけるｐＨが３．５以上５．０以下である、皮膚外用剤。
（II）皮膚外用剤組成物が定量吐出容器に収容されてなる皮膚外用剤であって、
　前記組成物は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を含有し、
　該組成物中に存在する前記酸のうち、酸型で存在するものを成分（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の前記成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である皮膚外用剤において、
　前記組成物が、さらにノニオン性増粘剤（Ｂ）を含有し、
　前記組成物の２５℃における粘度が、１００ｍＰａ・ｓ以上１０，０００ｍＰａ・ｓ以下である、皮膚外用剤。
＜３４＞
　前記（II）の態様の皮膚外用剤に用いる皮膚外用剤組成物の２５℃における粘度が、好ましくは１００ｍＰａ・ｓ以上５，０００ｍＰａ・ｓ以下であり、より好ましくは１００ｍＰａ・ｓ以上８，０００ｍＰａ・ｓ以下であり、さらに好ましくは１００ｍＰａ・ｓ以上２，０００ｍＰａ・ｓ以下であり、よりさらに好ましくは１００ｍＰａ・ｓ以上１，０００ｍＰａ・ｓ以下であり、よりさらに好ましくは１００ｍＰａ・ｓ以上８００ｍＰａ・ｓ以下、よりさらに好ましくは１００ｍＰａ・ｓ以上７００ｍＰａ・ｓ以下である、＜３３＞に記載の皮膚外用剤。
＜３５＞
　前記組成物が液状、ジェル状、クリーム状、又は泡状である、＜１＞～＜３４＞のいずれか１に記載の皮膚外用剤。
＜３６＞
　前記皮膚外用剤がリーブオン皮膚外用剤、好ましくは手指用のリーブオン皮膚外用剤である、＜１＞～＜３５＞のいずれか１に記載の皮膚外用剤。
＜３７＞
　皮膚外用剤組成物が定量吐出容器に収容されてなる皮膚外用製品であって、
　前記組成物は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を含有し、
　該組成物中に存在する前記酸のうち、酸型で存在するものを成分（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の前記成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である、皮膚外用製品。
＜３８＞
　乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を皮膚表面の適用部位に供給する方法であって、下記工程（Ｉ）及び工程（ＩＩ）を順に有する、方法。
工程（Ｉ）：前記適用部位を洗浄する工程
工程（ＩＩ）：前記成分（Ａ）を含有する組成物が収容された定量吐出容器から該組成物を１回の吐出操作により吐出して前記適用部位に供給する工程であって、該組成物中に存在する前記酸のうち、酸型で存在するものを（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である、工程 <27>
The viscosity of the composition at 25° C. is preferably 1.0 mPa·s or more, more preferably 2.0 mPa·s or more, still more preferably 3.0 mPa·s or more, and preferably 30,000 mPa·s or less. More preferably 25,000 mPa s or less, still more preferably 10,000 mPa s or less, still more preferably 8,000 mPa s or less, still more preferably 6,500 mPa s or less, still more preferably 5,000 mPa s s or less, 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, according to any one of <1> to <26> Skin external agent.
<28>
The metered discharge container for containing the composition is a stroke type and pump type pressure container, and the viscosity of the composition at 25° C. is more preferably 5.0 mPa·s or more, still more preferably 100 mPa·s. The external preparation for skin according to <27>, which is s or more.
<29>
The metered discharge container containing the composition is a stroke-type and spray-type push-type container, and the viscosity of the composition at 25° C. is more preferably 800 mPa·s or less, still more preferably 500 mPa·s or less. , Still more preferably 300 mPa s or less, still more preferably 200 mPa s or less, still more preferably 100 mPa s or less, still more preferably 5.0 mPa s or more, still more preferably 10.0 mPa s The skin external preparation according to <27>, which is the above.
<30>
The constant-dispensing container containing the composition is a squeeze-type press container, and the viscosity of the composition at 25° C. is more preferably 25,000 mPa·s or less, still more preferably 10,000 mPa·s or less. , more preferably 8,000 mPa s or less, still more preferably 6,500 mPa s or less, still more preferably 2,000 mPa s or less, still more preferably 100 mPa s or more, still more preferably 500 mPa · The external preparation for skin according to <27>, which is s or more.
<31>
The metered discharge container for containing the composition is an electric dispenser type container, and the viscosity of the composition at 25° C. is more preferably 800 mPa·s or less, still more preferably 500 mPa·s or less, and still more preferably 300 mPa. s or less, more preferably 200 mPa s or less, still more preferably 100 mPa s or less, still more preferably 5.0 mPa s or more, still more preferably 10.0 mPa s or more, <27 >.
<32>
<1> The pH of the composition at 25°C is preferably 3.5 to 5.0, more preferably 3.5 to 4.5, even more preferably 3.7 to 4.5. The skin external preparation according to any one of <31>.
<33>
The external preparation for skin according to any one of <1> to <32>, which is an embodiment of (I) or (II) below.
(I) An external skin preparation comprising an external skin preparation composition contained in a metered discharge container,
The composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid,
Among the acids present in the composition, when an acid present in an acid form is defined as the component (A1), the component (A1 ) content of 0.05 mg or more and 80 mg or less,
The component (A) is lactic acid or a salt thereof,
The mass ratio [(C)/(A)] of the organic acid other than the component (A) or a salt thereof (C) to the component (A) in the composition is less than 1;
An external preparation for skin, wherein the composition has a pH of 3.5 or more and 5.0 or less at 25°C.
(II) An external skin preparation comprising an external skin preparation composition contained in a metered discharge container,
The composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid,
Among the acids present in the composition, when an acid present in an acid form is defined as the component (A1), the component (A1 ) content of 0.05 mg or more and 80 mg or less,
The composition further contains a nonionic thickener (B),
An external preparation for skin, wherein the composition has a viscosity of 100 mPa·s or more and 10,000 mPa·s or less at 25°C.
<34>
The viscosity at 25° C. of the external skin preparation composition used in the external skin preparation of the aspect (II) is preferably 100 mPa·s or more and 5,000 mPa·s or less, more preferably 100 mPa·s or more and 8,000 mPa·s. s or less, more preferably 100 mPa s or more and 2,000 mPa s or less, even more preferably 100 mPa s or more and 1,000 mPa s or less, still more preferably 100 mPa s or more and 800 mPa s or less. , and more preferably 100 mPa·s or more and 700 mPa·s or less, the external preparation for skin according to <33>.
<35>
The external preparation for skin according to any one of <1> to <34>, wherein the composition is liquid, gel, cream, or foam.
<36>
The external skin preparation according to any one of <1> to <35>, wherein the external skin preparation is a leave-on skin preparation, preferably a leave-on skin preparation for fingers.
<37>
An external skin product comprising an external skin preparation composition contained in a metered discharge container,
The composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid,
Among the acids present in the composition, when an acid present in an acid form is used as the component (A1), the component (A1 ) content is 0.05 mg or more and 80 mg or less.
<38>
A method of supplying one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid to an application site on the skin surface, comprising the following steps (I) and (II) in order. have, method.
Step (I): Washing the application site Step (II): Dispensing the composition containing the component (A) from a metered discharge container containing the composition in one discharge operation and applying the composition In the step of supplying to the site, among the acids present in the composition, when the acid present in the acid form is (A1), it is discharged from the fixed amount discharge container by one discharge operation. A step in which the content of component (A1) in the composition is 0.05 mg or more and 80 mg or less
　以下、本発明を実施例により説明するが、本発明は実施例の範囲に限定されない。なお本実施例において、各種測定及び評価は以下の方法により行った。 The present invention will be described below with reference to examples, but the present invention is not limited to the scope of the examples. In addition, in the present Examples, various measurements and evaluations were performed by the following methods.
（ナトリウムイオン濃度）
　皮膚外用剤組成物のナトリウムイオン濃度は、ｐＨ調整剤（濃度１ｍｏｌ／Ｌの水酸化ナトリウム水溶液）の配合量から計算で求めた。
　なお、本実施例及び比較例の組成物に含まれる金属イオンはナトリウムイオンのみであるとみなす。 (Sodium ion concentration)
The sodium ion concentration of the external skin preparation composition was obtained by calculation from the blended amount of the pH adjuster (sodium hydroxide aqueous solution with a concentration of 1 mol/L).
The metal ions contained in the compositions of Examples and Comparative Examples are considered to be only sodium ions.
（粘度）
　皮膚外用剤組成物の粘度は、２５℃において振動式粘度計（（株）セコニック製「ＶＭ－１０ＡＬ」を用いて３回測定し、その平均値とした。
　対象の粘度に応じた測定条件は以下である：
・粘度：１～１００ｍＰａ・ｓ
　治具Ｍ１、回転数６０ｒｐｍ
・粘度１００ｍＰａ・ｓ超１，０００ｍＰａ・ｓ以下
　治具Ｍ２、回転数３０ｒｐｍ
・粘度１，０００ｍＰａ・ｓ超１０，０００ｍＰａ・ｓ以下
　治具Ｍ３、回転数１２ｒｐｍ
・粘度１０，０００ｍＰａ・ｓ超１００，０００ｍＰａ・ｓ以下
　治具Ｍ４、回転数６ｒｐｍ (viscosity)
The viscosity of the external skin preparation composition was measured three times at 25° C. using a vibrating viscometer ("VM-10AL" manufactured by Sekonic Co., Ltd.), and the average value was obtained.
The measurement conditions according to the target viscosity are as follows:
・Viscosity: 1 to 100mPa・s
Jig M1, rotation speed 60 rpm
・Viscosity over 100 mPa・s and 1,000 mPa・s or less Jig M2, rotation speed 30 rpm
・Viscosity over 1,000 mPa s and 10,000 mPa s or less Jig M3, rotation speed 12 rpm
・Viscosity over 10,000 mPa s and 100,000 mPa s or less Jig M4, rotation speed 6 rpm
（ｐＨ）
　皮膚外用剤組成物のｐＨは、２５℃において電極６３６７－１０Ｄ（（株）堀場製作所製）を用いて測定した。 (pH)
The pH of the external skin preparation composition was measured at 25° C. using an electrode 6367-10D (manufactured by Horiba, Ltd.).
（皮膚外用剤組成物中の成分（Ａ１）の含有量）
　皮膚外用剤組成物中の成分（Ａ１）の含有量（質量％）は、組成物中に存在する成分（Ａ）に由来する酸のうち、酸型で存在するものを成分（Ａ１）、解離型で存在するものを成分（Ａ２）とした場合に、以下の計算式より求められる。
　　皮膚外用剤組成物中の成分（Ａ１）の含有量（質量％）＝組成物中の成分（Ａ）の含有量（質量％）×｛組成物中のモル比［（Ａ１）／｛（Ａ１）＋（Ａ２）］｝
　また、吐出された組成物中の成分（Ａ１）の含有量（ｍｇ）は、以下の計算式より求められる。
　　吐出された組成物中の成分（Ａ１）の含有量（ｍｇ）＝組成物の質量（ｇ）×１０００×組成物中の成分（Ａ）の含有量（質量％）×｛組成物中のモル比［（Ａ１）／｛（Ａ１）＋（Ａ２）］｝÷１００ (Content of component (A1) in external skin preparation composition)
The content (% by mass) of the component (A1) in the external skin preparation composition is defined as, among acids derived from the component (A) present in the composition, the component (A1), which exists in an acid form, is dissociated. When the component (A2) is present in the form, it is obtained from the following formula.
Content (% by mass) of component (A1) in external skin preparation composition = content (% by mass) of component (A) in composition × {molar ratio in composition [(A1)/{(A1 ) + (A2)]}
Also, the content (mg) of the component (A1) in the ejected composition is determined by the following formula.
Content (mg) of component (A1) in the discharged composition = mass (g) of composition x 1000 x content (mass%) of component (A) in composition x {moles in composition Ratio [(A1)/{(A1)+(A2)]}/100
　ここで、「組成物中のモル比［（Ａ１）／｛（Ａ１）＋（Ａ２）］」は、以下の計算により求められる。以下の記載において、成分（Ａ１）のモル量を「ＨＡ」、成分（Ａ２）のモル量を「Ａ－」と表記する。
　　ｐＨ＝ｐＫａ＋ｌｏｇ（Ａ－／ＨＡ）
　　ｌｏｇ（Ａ－／ＨＡ）＝ｐＨ－ｐＫａ
　　Ａ－／ＨＡ＝１０＾（ｐＨ－ｐＫａ）
　　Ａ－＝１０＾（ｐＨ－ｐＫａ）×ＨＡ
　上記より、モル比［（Ａ１）／｛（Ａ１）＋（Ａ２）］は
　　ＨＡ／（ＨＡ＋Ａ－）＝ＨＡ／（ＨＡ＋１０＾（ｐＨ－ｐＫａ）×ＨＡ）
　　＝１／（１＋１０＾（ｐＨ－ｐＫａ））
　ここで、成分（Ａ）として乳酸を用いた場合（ｐＫａ＝３．８６）、
　　モル比［乳酸／（乳酸＋乳酸イオン）］＝１／（１＋１０＾（ｘ－３．８６））
　　（ｘは、組成物のｐＨ又は皮膚表面のｐＨを示す。） Here, the "molar ratio [(A1)/{(A1)+(A2)] in the composition" is obtained by the following calculation. In the following description, the molar amount of component (A1) is denoted as "HA" and the molar amount of component (A2) is denoted as " A- ".
pH = pKa + log( A- /HA)
log( A- /HA) = pH-pKa
A − /HA=10̂(pH−pKa)
A − = 10̂(pH−pKa)×HA
From the above, the molar ratio [(A1) / {(A1) + (A2)] is HA / (HA + A - ) = HA / (HA + 10 ^ (pH-pKa) × HA)
= 1/(1+10^(pH-pKa))
Here, when lactic acid is used as the component (A) (pKa = 3.86),
Molar ratio [lactic acid/(lactic acid + lactate ion)] = 1/(1 + 10 ^ (x - 3.86))
(x indicates the pH of the composition or the pH of the skin surface.)
　なお、成分（Ａ）が複数の成分からなる場合は、以下のような算出方法を本発明では定義する。
　組成物のｐＨを先述の方法で測定し、複数成分のそれぞれのｐＫａを上記の計算式に代入することで、それぞれの成分におけるモル比［（Ａ１）／｛（Ａ１）＋（Ａ２）］を求める。次に、それぞれの成分におけるモル比［（Ａ１）／｛（Ａ１）＋（Ａ２）］を足し合わせることで、複数種の成分（Ａ）を用いた場合におけるモル比［（Ａ１）／｛（Ａ１）＋（Ａ２）］を得ることができる。 In addition, when the component (A) consists of a plurality of components, the following calculation method is defined in the present invention.
By measuring the pH of the composition by the method described above and substituting the pKa of each of the multiple components into the above formula, the molar ratio of each component [(A1) / {(A1) + (A2)] demand. Next, by adding the molar ratio [(A1) / {(A1) + (A2)] in each component, the molar ratio [(A1) / {( A1)+(A2)] can be obtained.
実施例１～１２、比較例１～８（皮膚外用剤組成物の調製及び評価）
　表１～２に示す量の各成分を配合し、室温にて混合した後、ｐＨ調整剤として濃度１ｍｏｌ／Ｌの塩酸水溶液及び／又は濃度１ｍｏｌ／Ｌの水酸化ナトリウム水溶液を用いて各表に記載のｐＨに調整し、皮膚外用剤組成物を調製した。表１～２に記載した配合量は、各成分の有効成分量（質量％）である。
　この皮膚外用剤組成物を定量吐出容器に収容後、表１及び表２に記載の量で吐出させ、次のモデル実験を行った。具体的には、ピペットマン（ギルソン製）を用いて、表１及び表２に記載の組成物を、後述する方法により、両手の掌全体に塗り広げた条件に相当する量を皮膚表面に適用し、ｉｎ　ｖｉｖｏ殺菌性及び皮膚刺激性を評価した。
　なお、「両手の掌全体に塗り広げた条件に相当する量」とは、吐出した組成物の量（ｇ）を両手の掌の平均面積である５００ｃｍ２で除した量をいう。両手の掌の平均面積の値５００ｃｍ２は、Hyuk　Choi　et　al.,　”Palm　surface　area　database　and　estimation　formula　in　Korean　children　using　the　alginate　method”　(Applied　Ergonomics,Vol.42（2011）,873-882）のTable2に記載の、片手の表面積の相加平均値であるTPSA（total　palm　surface　area　mean　palm　area　with　fingers）の値に基づいて概算した値である。より詳細には、Table　2に記載の男性のTPSAのTotal値（ｃｍ２）と女性のTPSAのTotal値（ｃｍ２）の相加平均値を算出し、この２倍の値を両手の掌の平均面積とした。 Examples 1 to 12, Comparative Examples 1 to 8 (Preparation and Evaluation of External Skin Preparation Composition)
After blending each component in the amount shown in Tables 1 and 2 and mixing at room temperature, using a hydrochloric acid aqueous solution with a concentration of 1 mol / L and / or a sodium hydroxide aqueous solution with a concentration of 1 mol / L as a pH adjuster A skin external preparation composition was prepared by adjusting the pH as described. The blending amounts shown in Tables 1 and 2 are the active ingredient amounts (% by mass) of each component.
After containing this skin external preparation composition in a metered discharge container, the amount shown in Tables 1 and 2 was discharged, and the following model experiment was conducted. Specifically, using a Pipetman (manufactured by Gilson), the compositions shown in Tables 1 and 2 were applied to the skin surface in an amount corresponding to the condition of spreading over the entire palms of both hands by the method described later. , in vivo bactericidal and skin irritation properties were evaluated.
The term "amount corresponding to the condition of spreading over the entire palms of both hands" refers to the amount obtained by dividing the discharged composition amount (g) by 500 cm 2 , which is the average area of the palms of both hands. The value of the average palm area of 500 cm 2 of both hands is obtained from Hyuk Choi et al., ``Palm surface area database and estimation formula in Korean children using the alginate method'' (Applied Ergonomics, Vol.42 (2011), 873-882). It is a value estimated based on the value of TPSA (total palm surface area mean palm area with fingers) described in Table 2, which is the arithmetic mean value of the surface area of one hand. More specifically, the arithmetic mean of the total TPSA value (cm 2 ) for men and the total TPSA value (cm 2 ) for women shown in Table 2 is calculated, and double this value is measured on the palms of both hands. average area.
（菌液の調製）
　ｉｎ　ｖｉｖｏ殺菌性評価には、下記方法により調製したセラチア菌の菌液を用いた。
　セラチア菌としてはＮＢＲＣ１２６４８株を用いた。この菌を、ＬＢ液体培地にて培養し、遠心により菌体を回収した後、純水を用いてＯＤ６００＝１０になるように調整した。 (Preparation of bacterial solution)
For in vivo bactericidal evaluation, a serratia bacterium solution prepared by the following method was used.
NBRC12648 strain was used as Serratia. This bacterium was cultured in an LB liquid medium, collected by centrifugation, and adjusted to OD 600 =10 using pure water.
（ｉｎ　ｖｉｖｏ殺菌性：表１）
　被験者の前腕内側部を「ビオレｕ　Ｒｇ」（花王（株）製）を用いて洗浄した。５～１０分待機後、皮膚外用剤組成物を、１回の吐出操作により定量吐出容器から吐出し、前腕内側部の皮膚表面１ｃｍ２（１ｃｍ×１ｃｍ）の範囲に、両手の掌全体に塗り広げた条件に相当する量になるよう適用し塗り広げた。定量吐出容器の種類、１回の吐出操作により吐出された皮膚外用剤組成物の量は表１に記載の通りである。
　５分間静置して乾燥した後、前記方法で調整したセラチア菌液を、組成物適用後の皮膚表面に一定量（１μＬ／ｃｍ２）塗布した。この状態で３分静置して乾燥させた後、スワブ２本を用いて塗布した菌液を回収した。回収した菌を氷冷することで反応（組成物の菌液への作用）を停止させた。
　次いで、インキュベーションリーダー「ＨｉＴＳ」（（株）サイニクス製）を用いて下記方法により生存菌数を測定して、菌数の減少量（生存菌数／初期の生菌数）を確認した。
　インキュベーションリーダー「ＨｉＴＳ」中で３７℃にて液体培養し、波長６００ｎｍにおける吸光度（濁度）を経時で測定して、菌液中の生菌数の増殖曲線を作成した。同時に既知の生菌数を有する菌液を段階希釈し、同様に培養及び増殖曲線の作成を行い、一定の濁度に到達する時間と生菌数との検量線を作成した。一定濁度に到達するまでの時間と検量線の関係より、反応停止後の菌液中の生存菌数を推定し、菌数の減少量を確認した。
　菌数の減少度合い（対数減少値）については、上記菌数減少量の－ｌｏｇ値をとり、表１に示した。この値が大きいほど、ｉｎ　ｖｉｖｏ殺菌性が高いことを意味する。 (In vivo bactericidal activity: Table 1)
The inner part of the forearm of the subject was washed using "Biore u Rg" (manufactured by Kao Corporation). After waiting for 5 to 10 minutes, the external skin preparation composition is discharged from the metered discharge container in one discharging operation, and applied to the entire palms of both hands in the range of 1 cm 2 (1 cm × 1 cm) of the skin surface on the inside of the forearm. An amount corresponding to the spread conditions was applied and spread. Table 1 shows the types of fixed-quantity discharge containers and the amount of the external skin preparation composition discharged by one discharge operation.
After allowing to stand for 5 minutes to dry, a certain amount (1 μL/cm 2 ) of the Serratia bacterium solution prepared by the above method was applied to the skin surface after application of the composition. After standing in this state for 3 minutes to dry, the applied bacterial solution was collected using two swabs. The reaction (action of the composition on the bacterial solution) was stopped by ice-cooling the recovered bacteria.
Then, using an incubation reader "HiTS" (manufactured by Cynix Co., Ltd.), the number of surviving bacteria was measured by the following method to confirm the amount of decrease in the number of bacteria (number of surviving bacteria/initial number of viable bacteria).
Liquid culture was performed at 37° C. in an incubation reader “HiTS”, absorbance (turbidity) at a wavelength of 600 nm was measured over time, and a growth curve of the number of viable cells in the bacterial solution was created. At the same time, a bacterial solution with a known number of viable bacteria was serially diluted, cultured in the same manner and a growth curve was created, and a calibration curve between the time to reach a certain turbidity and the number of viable bacteria was created. Based on the relationship between the time required to reach a constant turbidity and the calibration curve, the number of surviving bacteria in the bacterial solution after stopping the reaction was estimated, and the decrease in the number of bacteria was confirmed.
Regarding the degree of reduction in the number of bacteria (logarithmic reduction value), the -log value of the amount of reduction in the number of bacteria was taken and shown in Table 1. A larger value means a higher in vivo bactericidal activity.
（ｉｎ　ｖｉｖｏ殺菌性：表２）
　上記において、表２に記載の皮膚外用剤組成物（実施例５、比較例１及び比較例８）を用い、該組成物を皮膚表面に塗布した後の静置時間を１、２、３、４、５分間とし、それぞれにデータを取得したこと以外は、上記と同様の操作を行った。菌数の減少度合い（対数減少値）については、菌数減少量の－ｌｏｇ値をとり、表２に示した。 (In vivo bactericidal activity: Table 2)
In the above, the external skin preparation composition (Example 5, Comparative Example 1 and Comparative Example 8) shown in Table 2 was used, and the standing time after applying the composition to the skin surface was 1, 2, 3, The same operation as above was performed except that the data was obtained for each of 4 and 5 minutes. Table 2 shows the -log value of the amount of decrease in the number of bacteria for the degree of decrease in the number of bacteria (logarithmic decrease value).
（皮膚刺激性）
　被験者の前腕内側部を「ビオレｕ　Ｒｇ」（花王（株）製）を用いて洗浄し、さらに水道水及び純水で洗浄した。５～１０分待機後、皮膚外用剤組成物を５回の吐出操作により定量吐出容器から吐出し、直径９ｍｍのろ紙（パッチテスター「トリイ」、リバテープ製薬（株）製）に両手の掌全体に塗り広げた条件に相当する量になるよう適用し浸み込ませた。このろ紙を前腕内側部の皮膚表面に載置し、上からシールして、６０分間静置した。６０分後にシールを剥がし、その３０分後に皮膚表面に赤みが出ているか否かを目視観察した。表１中、赤みが出ていない場合を「－」、赤みがでている場合を「＋」と表記した。「－」評価であれば皮膚刺激性がないことを意味する。 (skin irritation)
The inner part of the forearm of the subject was washed with "Bioré u Rg" (manufactured by Kao Corporation), and further washed with tap water and pure water. After waiting for 5 to 10 minutes, the external skin preparation composition is discharged from the metered discharge container by 5 discharge operations, and is applied to the entire palm of both hands on a filter paper with a diameter of 9 mm (patch tester "Torii", manufactured by Livetape Pharmaceutical Co., Ltd.). An amount corresponding to the spread conditions was applied and allowed to soak in. This filter paper was placed on the skin surface of the inside of the forearm, sealed from above, and allowed to stand for 60 minutes. After 60 minutes, the seal was peeled off, and 30 minutes later, whether or not the skin surface was reddish was visually observed. In Table 1, "-" indicates no redness, and "+" indicates redness. A "-" rating means no skin irritation.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
＜組成物中の配合成分＞
　（Ａ）乳酸：富士フイルム和光純薬（株）製「乳酸（アクティブ：９０％）」
　（Ｃ１）クエン酸：富士フイルム和光純薬（株）製
　（Ｃ２）ピロリドンカルボン酸：富士フイルム和光純薬（株）製
　ｐＨ調整剤：濃度１ｍｏｌ／Ｌの塩酸水溶液及び／又は濃度１ｍｏｌ／Ｌの水酸化ナトリウム水溶液
・塩酸水溶液：富士フイルム和光純薬（株）製「塩酸（１ｍｏｌ／Ｌ）」
・水酸化ナトリウム水溶液：関東化学（株）製「ＮａＯＨ（水酸化ナトリウム水溶液）４８％」を水酸化ナトリウム１ｍｏｌ／Ｌ水溶液になるように調整して使用した。
　塩化ベンザルコニウム：東京化成工業（株）製「塩化ベンザルコニウム（５０％水溶液）」 <Ingredients in the composition>
(A) Lactic acid: Fujifilm Wako Pure Chemical Co., Ltd. “lactic acid (active: 90%)”
(C1) Citric acid: manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd. (C2) Pyrrolidone carboxylic acid: manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd. pH adjuster: hydrochloric acid aqueous solution with a concentration of 1 mol / L and / or with a concentration of 1 mol / L Sodium hydroxide aqueous solution/hydrochloric acid aqueous solution: FUJIFILM Wako Pure Chemical Co., Ltd. “Hydrochloric acid (1 mol / L)”
· Sodium hydroxide aqueous solution: Kanto Kagaku Co., Ltd. "NaOH (sodium hydroxide aqueous solution) 48%" was used after being adjusted to become a sodium hydroxide 1 mol/L aqueous solution.
Benzalkonium chloride: "Benzalkonium chloride (50% aqueous solution)" manufactured by Tokyo Chemical Industry Co., Ltd.
　表１より、本実施例の皮膚外用剤を用いると、皮膚表面の殺菌性が高く、且つ皮膚刺激性を抑制することができることがわかる。また表２に示すように、本実施例で用いる皮膚外用剤組成物は、既存の殺菌剤である塩化ベンザルコニウム水溶液（比較例８）とは異なり、皮膚に塗布した後、時間が経過するにつれて殺菌性が低下することなく、寧ろ向上する傾向があることがわかる。 From Table 1, it can be seen that the use of the external preparation for skin of this example has high bactericidal activity on the skin surface and can suppress skin irritation. In addition, as shown in Table 2, the skin external preparation composition used in this example, unlike the benzalkonium chloride aqueous solution (Comparative Example 8), which is an existing disinfectant, was applied to the skin for some time. It can be seen that the bactericidal activity tends to improve rather than decrease as the temperature increases.
実施例１３～２９
（皮膚外用剤組成物の吐出試験）
　表３に示す量の各成分を配合し、室温にて混合した後、ｐＨ調整剤として濃度１ｍｏｌ／Ｌの塩酸水溶液及び／又は濃度１ｍｏｌ／Ｌの水酸化ナトリウム水溶液を用いて表３に記載のｐＨに調整し、皮膚外用剤組成物を調製した。表３に記載した配合量は、各成分の有効成分量（質量％）である。
　この皮膚外用剤組成物を表３に記載の定量吐出容器（ストローク式のスプレー容器Ｘ又はポンプ容器Ｙ）に充填し、容器入り皮膚外用剤を得た。皮膚外用剤組成物の充填量は、スプレー容器Ｘには５０ｍＬ、ポンプ容器Ｙには１２０ｍＬとした。また、各々吐出操作を１回行い、１回の吐出操作により吐出される組成物量を確認した。１回の吐出操作は、定量吐出容器のストロークに７ｋｇの荷重を３秒間かけた状態とした。 Examples 13-29
(Ejection test of external skin preparation composition)
After blending each component in the amount shown in Table 3 and mixing at room temperature, using a hydrochloric acid aqueous solution with a concentration of 1 mol / L and / or a sodium hydroxide aqueous solution with a concentration of 1 mol / L as a pH adjuster. The pH was adjusted to prepare a skin external preparation composition. The blending amount shown in Table 3 is the active ingredient amount (% by mass) of each component.
This external skin preparation composition was filled in a metered discharge container (stroke-type spray container X or pump container Y) shown in Table 3 to obtain a container-packed external skin preparation. The filling amount of the skin external preparation composition was 50 mL in the spray container X and 120 mL in the pump container Y. In addition, each ejection operation was performed once, and the amount of the composition ejected by one ejection operation was confirmed. One discharge operation was performed by applying a load of 7 kg to the stroke of the metered discharge container for 3 seconds.
（ｉｎ　ｖｉｖｏ殺菌性）
　表１のｉｎ　ｖｉｖｏ殺菌性と同様の方法で評価を行った。 (in vivo bactericidal)
Evaluation was performed in the same manner as in vivo bactericidal activity in Table 1.
（使用感）
　表３に記載の皮膚外用剤組成物１．０ｇを吐出し、両手全体に馴染むまで塗り広げて乾燥させた。その後、指先を２０℃、８０ｍＬ／ｓの流量の水道水で１秒間濡らした後、指先を擦り合わせた際のきしみ感を評価した。評価は専門パネラー５名により下記の基準で行い、スコアの平均値を評価値とした。
＜定量吐出容器Ｘを用いた場合＞
　１：実施例１３よりきしみ感を強く感じる
　２：実施例１３よりややきしみ感を感じる
　３：実施例１３と同等
　４：実施例１３よりややきしみ感が弱い
　５：実施例１３よりきしみ感が弱い
＜定量吐出容器Ｙを用いた場合＞
　１：実施例１６よりきしみ感を強く感じる
　２：実施例１６よりややきしみ感を感じる
　３：実施例１６と同等
　４：実施例１６よりややきしみ感が弱い
　５：実施例１６よりきしみ感が弱い (feeling of use)
1.0 g of the composition for external use for skin shown in Table 3 was discharged, spread over both hands until it was absorbed, and dried. Thereafter, the fingertips were wetted with tap water at 20° C. and a flow rate of 80 mL/s for 1 second, and then the squeaky feeling when the fingertips were rubbed together was evaluated. Evaluation was performed by five expert panelists according to the following criteria, and the average score was used as the evaluation value.
<Using Fixed Dispensing Container X>
1: More squeaky than in Example 13 2: Slightly more squeaky than in Example 13 3: Equivalent to Example 13 4: Slightly less squeaky than in Example 13 5: Less squeaky than in Example 13 <When using the fixed quantity discharge container Y>
1: More squeaky than in Example 16 2: Slightly more squeaky than in Example 16 3: Equivalent to Example 16 4: Slightly less squeaky than in Example 16 5: Less squeaky than in Example 16
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
＜定量吐出容器の種類＞
Ｘ：ストローク式スプレータイプ容器（スプレーヘッド：竹本容器（株）製「Ｚ－１５５－Ｃ１１０」）、容量５０ｍＬ
Ｙ：花王（株）製「ａｎｄ　ａｎｄ　カスタムエッセンス」用ストローク式ポンプタイプ容器、容量１２０ｍＬ <Kinds of fixed quantity discharge container>
X: Stroke type spray type container (spray head: “Z-155-C110” manufactured by Takemoto Container Co., Ltd.), capacity 50 mL
Y: Stroke pump type container for "and and custom essence" manufactured by Kao Corporation, capacity 120 mL
＜組成物中の配合成分＞
　（Ａ）乳酸：富士フイルム和光純薬（株）製「乳酸（アクティブ：９０％）」
　（Ｂ１）ポリビニルアルコール：日本酢ビ・ポバール（株）製「ＪＣ－４０」、重合度４，０００、ケン価度９９．０～９９．５モル％
　（Ｂ２）ヒドロキシエチルセルロース１：Ａｓｈｌａｎｄ（株）製「Ｎａｔｒｏｓｏｌ　ＨＥＣ　２５０ＨＨＸ」
　（Ｂ３）ヒドロキシエチルセルロース２：（株）ダイセル製「ＨＥＣ　ダイセル　８５０ＳＥ」
　ｐＨ調整剤：濃度１ｍｏｌ／Ｌの塩酸水溶液及び／又は濃度１ｍｏｌ／Ｌの水酸化ナトリウム水溶液
・塩酸水溶液：富士フイルム和光純薬（株）製「塩酸（１ｍｏｌ／Ｌ）」
・水酸化ナトリウム水溶液：関東化学（株）製「ＮａＯＨ（水酸化ナトリウム水溶液）４８％」を水酸化ナトリウム１ｍｏｌ／Ｌ水溶液になるように調整して使用した。 <Ingredients in the composition>
(A) Lactic acid: Fujifilm Wako Pure Chemical Co., Ltd. “lactic acid (active: 90%)”
(B1) Polyvinyl alcohol: "JC-40" manufactured by Japan Vinyl Acetate & Poval Co., Ltd., polymerization degree 4,000, ken value 99.0 to 99.5 mol%
(B2) Hydroxyethyl cellulose 1: "Natrosol HEC 250HHX" manufactured by Ashland Co., Ltd.
(B3) Hydroxyethyl cellulose 2: "HEC Daicel 850SE" manufactured by Daicel Corporation
pH adjuster: 1 mol/L hydrochloric acid aqueous solution and/or 1 mol/L sodium hydroxide aqueous solution/hydrochloric acid aqueous solution: FUJIFILM Wako Pure Chemical Co., Ltd. “Hydrochloric acid (1 mol/L)”
· Sodium hydroxide aqueous solution: Kanto Kagaku Co., Ltd. "NaOH (sodium hydroxide aqueous solution) 48%" was used after being adjusted to become a sodium hydroxide 1 mol/L aqueous solution.
　本発明によれば、優れた殺菌又は殺ウイルス性を発揮し、且つ、皮膚刺激性の低い皮膚外用剤を提供できる。 According to the present invention, it is possible to provide an external preparation for skin that exhibits excellent bactericidal or virucidal properties and has low skin irritation.

Claims (11)

  1. 　皮膚外用剤組成物が定量吐出容器に収容されてなる皮膚外用剤であって、
    　前記組成物は、乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を含有し、
    　該組成物中に存在する前記酸のうち、酸型で存在するものを成分（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の前記成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である、皮膚外用剤。     An external skin preparation comprising an external skin preparation composition contained in a fixed-quantity discharge container,
    The composition contains one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid,
    Among the acids present in the composition, when an acid present in an acid form is defined as the component (A1), the component (A1 ) content is 0.05 mg or more and 80 mg or less.
  2. 　前記定量吐出容器から１回の吐出操作により吐出される前記組成物の量が０．０５ｇ以上３．０ｇ以下である、請求項１に記載の皮膚外用剤。 The external preparation for skin according to claim 1, wherein the amount of the composition discharged from the fixed quantity discharge container in one discharge operation is 0.05 g or more and 3.0 g or less.
  3. 　前記組成物の２５℃における粘度が１．０ｍＰａ・ｓ以上１０，０００ｍＰａ・ｓ以下である、請求項１又は２に記載の皮膚外用剤。 The skin external preparation according to claim 1 or 2, wherein the composition has a viscosity at 25°C of 1.0 mPa·s or more and 10,000 mPa·s or less.
  4. 　前記組成物の２５℃におけるｐＨが３．５以上５．０以下である、請求項１～３のいずれか１項に記載の皮膚外用剤。 The skin external preparation according to any one of claims 1 to 3, wherein the composition has a pH of 3.5 or more and 5.0 or less at 25°C.
  5. 　前記組成物中の前記成分（Ａ）の含有量が０．０５質量％以上１０質量％以下である、請求項１～４のいずれか１項に記載の皮膚外用剤。 The skin external preparation according to any one of claims 1 to 4, wherein the content of said component (A) in said composition is 0.05% by mass or more and 10% by mass or less.
  6. 　前記組成物中の前記成分（Ａ１）の含有量が０．０２質量％以上１０質量％以下である、請求項１～５のいずれか１項に記載の皮膚外用剤。 The skin external preparation according to any one of claims 1 to 5, wherein the content of said component (A1) in said composition is 0.02% by mass or more and 10% by mass or less.
  7. 　前記組成物中の金属イオン濃度が０．００２ｍｏｌ／Ｌ以上０．５０ｍｏｌ／Ｌ以下である、請求項１～６のいずれか１項に記載の皮膚外用剤。 The skin external preparation according to any one of claims 1 to 6, wherein the metal ion concentration in the composition is 0.002 mol/L or more and 0.50 mol/L or less.
  8. 　前記定量吐出容器がストローク式の押圧式容器であり、前記１回の吐出操作が、該容器をフルストロークで１回押圧する操作である、請求項１～７のいずれか１項に記載の皮膚外用剤。 The skin according to any one of claims 1 to 7, wherein the metered discharge container is a stroke-type press-type container, and the single discharge operation is an operation of pressing the container once with a full stroke. External agent.
  9. 　前記成分（Ａ）が乳酸又はその塩であり、
    　前記組成物中の、前記成分（Ａ）に対する、前記成分（Ａ）以外の有機酸又はその塩（Ｃ）の質量比［（Ｃ）／（Ａ）］が１未満であり、
    　前記組成物の２５℃におけるｐＨが３．５以上５．０以下である、請求項１～８のいずれか１項に記載の皮膚外用剤。     The component (A) is lactic acid or a salt thereof,
    The mass ratio [(C)/(A)] of the organic acid other than the component (A) or a salt thereof (C) to the component (A) in the composition is less than 1;
    The external preparation for skin according to any one of claims 1 to 8, wherein the composition has a pH of 3.5 to 5.0 at 25°C.
  10. 　前記組成物が、さらにノニオン性増粘剤（Ｂ）を含有し、
    　前記組成物の２５℃における粘度が、１００ｍＰａ・ｓ以上１０，０００ｍＰａ・ｓ以下である、請求項１～９のいずれか１項に記載の皮膚外用剤。     The composition further contains a nonionic thickener (B),
    The external preparation for skin according to any one of claims 1 to 9, wherein the composition has a viscosity at 25°C of 100 mPa·s or more and 10,000 mPa·s or less.
  11. 　乳酸、ピルビン酸及びウロカニン酸からなる群から選ばれる１種以上の酸又はその塩（Ａ）を皮膚表面の適用部位に供給する方法であって、下記工程（Ｉ）及び工程（ＩＩ）を順に有する、方法。
    工程（Ｉ）：前記適用部位を洗浄する工程
    工程（ＩＩ）：前記成分（Ａ）を含有する組成物が収容された定量吐出容器から該組成物を１回の吐出操作により吐出して前記適用部位に供給する工程であって、該組成物中に存在する前記酸のうち、酸型で存在するものを（Ａ１）とした場合に、前記定量吐出容器から１回の吐出操作により吐出される組成物中の前記成分（Ａ１）の含有量が０．０５ｍｇ以上８０ｍｇ以下である、工程     A method for supplying one or more acids or salts thereof (A) selected from the group consisting of lactic acid, pyruvic acid and urocanic acid to an application site on the surface of the skin, comprising the following steps (I) and (II) in order. have, method.
    Step (I): The step of washing the application site Step (II): The composition containing the component (A) is discharged from a metered discharge container containing the composition by one discharge operation, and the application is performed. In the step of supplying to the site, among the acids present in the composition, when the acid existing in the acid form is (A1), it is discharged from the fixed amount discharge container by one discharge operation. the content of the component (A1) in the composition is 0.05 mg or more and 80 mg or less;
PCT/JP2022/028041 2021-09-06 2022-07-19 External skin preparation WO2023032493A1 (en)

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GB1498160A (en) * 1975-01-09 1978-01-18 Dermacia Ab Agent for skin treatment and a wet diaper prepared therewith
EP1050297A2 (en) * 1999-05-03 2000-11-08 Fort James Corporation Lotionized tissue products containing a pH balance compound for the skin
JP2017025062A (en) * 2015-07-23 2017-02-02 ジョンソン・アンド・ジョンソン・コンシューマー・インコーポレイテッド TOPICAL DELIVERY OF SKIN COMPOSITIONS HAVING LOW pH
JP2019026592A (en) * 2017-07-28 2019-02-21 イーダ株式会社 Alcoholic disinfectant
JP2021161102A (en) * 2020-04-03 2021-10-11 花王株式会社 Method for protecting skin from bacteria or virus
WO2021246352A1 (en) * 2020-06-05 2021-12-09 花王株式会社 External dermatological composition for germicidal and virucidal use
WO2022034911A1 (en) * 2020-08-13 2022-02-17 花王株式会社 Composition for leave-on-type skin external preparation

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GB1498160A (en) * 1975-01-09 1978-01-18 Dermacia Ab Agent for skin treatment and a wet diaper prepared therewith
EP1050297A2 (en) * 1999-05-03 2000-11-08 Fort James Corporation Lotionized tissue products containing a pH balance compound for the skin
JP2017025062A (en) * 2015-07-23 2017-02-02 ジョンソン・アンド・ジョンソン・コンシューマー・インコーポレイテッド TOPICAL DELIVERY OF SKIN COMPOSITIONS HAVING LOW pH
JP2019026592A (en) * 2017-07-28 2019-02-21 イーダ株式会社 Alcoholic disinfectant
JP2021161102A (en) * 2020-04-03 2021-10-11 花王株式会社 Method for protecting skin from bacteria or virus
WO2021246352A1 (en) * 2020-06-05 2021-12-09 花王株式会社 External dermatological composition for germicidal and virucidal use
WO2022034911A1 (en) * 2020-08-13 2022-02-17 花王株式会社 Composition for leave-on-type skin external preparation

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