CN117897150A - External preparation for skin - Google Patents
External preparation for skin Download PDFInfo
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- CN117897150A CN117897150A CN202280059108.0A CN202280059108A CN117897150A CN 117897150 A CN117897150 A CN 117897150A CN 202280059108 A CN202280059108 A CN 202280059108A CN 117897150 A CN117897150 A CN 117897150A
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- skin
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- 238000002360 preparation method Methods 0.000 title claims abstract description 125
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- 239000002253 acid Substances 0.000 claims abstract description 65
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 claims abstract description 49
- 239000004310 lactic acid Substances 0.000 claims abstract description 48
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 48
- 150000003839 salts Chemical class 0.000 claims abstract description 45
- 229940107700 pyruvic acid Drugs 0.000 claims abstract description 25
- LOIYMIARKYCTBW-UHFFFAOYSA-N trans-urocanic acid Natural products OC(=O)C=CC1=CNC=N1 LOIYMIARKYCTBW-UHFFFAOYSA-N 0.000 claims abstract description 24
- LOIYMIARKYCTBW-OWOJBTEDSA-N trans-urocanic acid Chemical compound OC(=O)\C=C\C1=CNC=N1 LOIYMIARKYCTBW-OWOJBTEDSA-N 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims description 28
- 229910021645 metal ion Inorganic materials 0.000 claims description 14
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- 229910052783 alkali metal Inorganic materials 0.000 description 4
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- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 3
- RFRMMZAKBNXNHE-UHFFFAOYSA-N 6-[4,6-dihydroxy-5-(2-hydroxyethoxy)-2-(hydroxymethyl)oxan-3-yl]oxy-2-(hydroxymethyl)-5-(2-hydroxypropoxy)oxane-3,4-diol Chemical compound CC(O)COC1C(O)C(O)C(CO)OC1OC1C(O)C(OCCO)C(O)OC1CO RFRMMZAKBNXNHE-UHFFFAOYSA-N 0.000 description 3
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- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 3
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- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
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- 229910001415 sodium ion Inorganic materials 0.000 description 3
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- ZWVMLYRJXORSEP-UHFFFAOYSA-N 1,2,6-Hexanetriol Chemical compound OCCCCC(O)CO ZWVMLYRJXORSEP-UHFFFAOYSA-N 0.000 description 2
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- DSKYSDCYIODJPC-UHFFFAOYSA-N 2-butyl-2-ethylpropane-1,3-diol Chemical compound CCCCC(CC)(CO)CO DSKYSDCYIODJPC-UHFFFAOYSA-N 0.000 description 2
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- NCZPCONIKBICGS-UHFFFAOYSA-N 3-(2-ethylhexoxy)propane-1,2-diol Chemical compound CCCCC(CC)COCC(O)CO NCZPCONIKBICGS-UHFFFAOYSA-N 0.000 description 2
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- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 2
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- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
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- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
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- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
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- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
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- 230000002949 hemolytic effect Effects 0.000 description 1
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- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 229910052751 metal Inorganic materials 0.000 description 1
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- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
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- ZWLUXSQADUDCSB-UHFFFAOYSA-N phthalaldehyde Chemical compound O=CC1=CC=CC=C1C=O ZWLUXSQADUDCSB-UHFFFAOYSA-N 0.000 description 1
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- OJTDGPLHRSZIAV-UHFFFAOYSA-N propane-1,2-diol Chemical compound CC(O)CO.CC(O)CO OJTDGPLHRSZIAV-UHFFFAOYSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
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- 150000003460 sulfonic acids Chemical class 0.000 description 1
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Classifications
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P31/12—Antivirals
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- 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
Landscapes
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- Communicable Diseases (AREA)
- Dermatology (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cosmetics (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A skin external preparation comprising a composition for external use containing 1 or more acids selected from lactic acid, pyruvic acid and urocanic acid or a salt thereof (A) in a quantitative discharge container, wherein when the component (A1) in the acid form of the acids present in the composition is the component (A1), the content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg or more and 80mg or less.
Description
Technical Field
The present invention relates to an external preparation for skin.
Prior Art
As a result of recent investigation, many of the bacteria and viruses in daily life are exposed to infection. Contact infection is mainly caused by contact of a finger with an infected person of bacteria or viruses, a door handle, a handle, tableware, toys, other daily necessities, interior articles, and the like.
Methods for preventing bacterial or viral contact infection due to such contact behavior in daily life are required.
As a method for preventing contact infection by bacteria or viruses of a finger, a method of applying an alcohol disinfectant or the like to a finger to sterilize and disinfect is known. However, alcohols such as ethanol used as a sterilization and disinfection component have high volatility, and from the viewpoint of imparting a sterilizing and virus killing effect to fingers, the effect is not sufficiently sustained.
Therefore, methods of imparting a function of protecting a finger against bacteria or viruses have been studied. According to this method, an effect of preventing bacterial or viral infection can be obtained continuously, and thus contact infection can be prevented even in an environment where no toilet exists at an outgoing destination or the like. In particular, it is preferable in terms of preventing infection even when the contact with the object to be contacted to which bacteria or viruses are attached is repeated.
Japanese patent laying-open No. 2019-518720 (patent document 1) discloses a topical composition such as a finger disinfectant composition which can provide a long-lasting antibacterial effect, comprising: nicotinamide or derivatives thereof; a first quaternary ammonium salt comprising didecyl dimethyl ammonium chloride; second quaternary ammonium salts such as benzethonium chloride, benzalkonium chloride, and polydiallyl dimethyl ammonium chloride; as a cosmetically acceptable base.
Disclosure of Invention
The present invention relates to the following.
[1] A skin external preparation is prepared by storing a skin external preparation composition in a quantitative discharge container,
the composition contains at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or its salt (A),
when the component (A1) is the component (A1) in the acid form of the acid present in the composition, the content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg to 80 mg.
[2] A method for supplying at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or a salt (A) thereof to an application site on the skin surface, comprising the following steps (I) and (II) in this order:
step (I): cleaning the application part;
step (II): and a step of discharging the composition from a quantitative discharge container containing the composition containing the component (A) by a single discharge operation, and supplying the composition to the application site, wherein when the component (A1) in the acid form in the acid present in the composition is (A1), the content of the component (A1) in the composition discharged from the quantitative discharge container by a single discharge operation is 0.05mg to 80 mg.
Detailed Description
The amount of the bactericide and the antibacterial agent to be blended in the skin composition used in the technology disclosed in patent document 1 is substantially limited from the viewpoint of safety to the human body. Therefore, the bactericidal or virucidal activity of the skin by bactericides or antimicrobial agents is not sufficient, and further improvement is expected.
The present invention aims to provide an external preparation for skin which exhibits excellent bactericidal or antiviral properties and has low skin irritation.
The present inventors have found that the above-described problems can be solved by using a skin external preparation comprising a container in which a skin external preparation composition containing a specific organic acid or a salt thereof is contained so as to be capable of discharging the skin external preparation composition so as to satisfy specific conditions.
The present invention can provide an external preparation for skin which exhibits excellent bactericidal or antiviral properties and has low skin irritation.
[ definition ]
In the present specification, the "component (A1) in the acid form" means a component in the form of lactic acid, pyruvic acid and urocanic acid in the composition among 1 or more acids selected from lactic acid, pyruvic acid and urocanic acid derived from the component (a). In the following description, the component in the composition in the form of lactic acid ion, pyruvic acid ion, and urocanic acid ion is also referred to as "component (A2) in the form of dissociation" in the case of 1 or more acids selected from lactic acid, pyruvic acid, and urocanic acid derived from the component (a).
In the present specification, "sterilizing or virucidal" means sterilizing or virucidal of the skin surface to which the skin external composition is applied. For example, the bactericidal activity against Serratia can be specifically evaluated by the methods described in examples. The sterilization and virucidal activity against other bacteria and viruses can be evaluated by reference to common technical knowledge.
In the present specification, "exerting sterilization or virucidal" is a concept including imparting the following effects: (1) The skin external composition exhibits a bactericidal/virucidal effect on bacteria/viruses adhering to the skin surface after being applied to the skin surface; (2) The bactericidal/virucidal effects of the composition on skin-adhering bacteria/viruses; (3) The effect of adjusting the skin to the skin free from bacteria and viruses; (4) Protecting skin from bacteria and viruses to ensure hygienic effects; (5) An effect of preventing the transmission of bacteria and viruses through the skin and contact infection; and (6) an effect of improving the infection resistance of the skin against bacteria and viruses.
[ skin external preparation ]
The external skin preparation of the present invention is obtained by storing a composition for external use (hereinafter, simply referred to as "composition") containing 1 or more acids selected from lactic acid, pyruvic acid and urocanic acid or a salt thereof (a) in a quantitative discharge container, wherein when the component (A1) is an acid type component among the acids contained in the composition, the content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg or more and 80mg or less.
That is, the external skin preparation of the present invention is an external skin preparation comprising the external skin preparation composition and the quantitative discharge container.
The external skin preparation of the present invention has the above composition, and thus exhibits excellent bactericidal or antiviral properties and is low in skin irritation.
The reason why the external skin preparation of the present invention exerts the above-described effects is not clear, but is presumed as follows.
The external skin preparation of the present invention uses the component (A) as a bactericidal or virucidal component. The inventors found that: lactic acid, pyruvic acid and urocanic acid as the component (A) are supplied from sweat glands and the like, and are originally present on human skin, particularly on fingers, and play a role in sterilizing and killing bacteria, viruses and the like. Thus, it is considered that: the composition for external use for skin containing the component (A) has a bactericidal or antiviral effect, but is less irritating to the skin and can be made into a composition having high safety to the human body.
Regarding the sterilization or virucidal action described above, it is known that: even for the composition containing the component (a), when the pH is low, the sterilization or virucidal activity is high. For example, lactic acid as the component (A) can be obtained in an aqueous solution as an acid form (CH 3 CH (OH) COOH) and dissociative (CH) 3 CH(OH)COO - ) The acid form has no charge and is easily absorbed into bacteria or viruses, and thus the acid form is considered to exhibit high bactericidal or virucidal activity.
On the other hand, the following concerns are also presented for the composition containing the component (a): in the case of compositions in the low pH region, skin irritation can occur.
Accordingly, the present inventors focused on the content of the component (A1) in the acid form in the above-mentioned acid in the skin external composition for application to the skin. And, found that: by storing the composition for external use for skin containing the component (a) in a quantitative discharge container and setting the component (A1) in the composition discharged from the container by one discharge operation to a specific range, excellent sterilization or virucidal activity can be exhibited and skin irritation can be reduced.
The external skin preparation of the present invention is obtained by storing the external skin preparation composition in the quantitative discharge container, and the content of the component (A1) contained in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg to 80 mg. When the content of the component (A1) in the discharged composition is in the above range, the composition is a skin external preparation which exhibits excellent bactericidal or antiviral properties and has low skin irritation. Further, the external preparation for skin of the present invention is controlled so that the "content of the component (A1) contained in the composition to be sprayed" is within the above-described range by one spraying operation, and therefore, the component (A1) which is an amount that exhibits excellent sterilization or virucidal activity and realizes low irritation to skin can be easily and stably supplied to skin.
The content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is preferably 0.1mg or more, more preferably 0.2mg or more, still more preferably 0.4mg or more, still more preferably 0.5mg or more, still more preferably 1.0mg or more, still more preferably 2.0mg or more, from the viewpoint of improving sterilization or virucidal properties, and from the viewpoint of easily suppressing skin irritation even when the composition is continuously applied to the skin, preferably 60mg or less, more preferably 50mg or less, still more preferably 45mg or less. The content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg or more and 80mg or less, preferably 0.1mg or more and 60mg or less, more preferably 0.2mg or more and 60mg or less, still more preferably 0.4mg or more and 50mg or less, still more preferably 0.5mg or more and 50mg or less, still more preferably 1.0mg or more and 45mg or less, and still more preferably 2.0mg or more and 45mg or less.
The content of the component (A1) in the composition discharged by one discharge operation can be calculated by the method described in the examples.
The content of the component (A1) in the composition discharged by one discharge operation can be controlled by the content of the component (a) in the composition used for the external skin preparation of the present invention, the pH of the composition, the viscosity of the composition, the type of the quantitative discharge container, the discharge amount by one discharge operation, or a combination thereof.
In the external skin preparation of the present invention, the amount of the composition discharged from the quantitative discharge container by one discharge operation is preferably 0.05g or more, more preferably 0.1g or more, still more preferably 0.2g or more, from the viewpoint of improving the bactericidal or antiviral properties and the coating properties on the skin, and is preferably 3.0g or less, more preferably 2.5g or less, still more preferably 2.0g or less, from the viewpoint of suppressing skin irritation and the viewpoint of suppressing dripping after application to the skin. The amount of the composition discharged from the quantitative discharge container by one discharge operation is preferably 0.05g or more and 3.0g or less, more preferably 0.1g or more and 2.5g or less, and still more preferably 0.2g or more and 2.0g or less.
< quantitative ejection Container >)
The external preparation for skin of the present invention is obtained by storing a composition for external use for skin containing at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or a salt (A) thereof in a quantitative discharge container.
In the present specification, the term "quantitative ejection container" refers to a container capable of storing a skin external agent composition and ejecting a substantially fixed amount of the skin external agent composition as the content of the container by performing an ejection operation.
The quantitative discharge container includes: a push type container such as a stroke type container and a squeeze type container; an electric dispenser container, etc. The disposable individual package type container is also included in the quantitative ejection container of the present invention.
Examples of the stroke-type push type container include pump type and spray type containers, and examples thereof include those described in japanese patent application laid-open publication No. 2019-51949. Further, as the squeeze-type squeeze container, there can be exemplified a squeeze-type squeeze container described in japanese patent application laid-open No. 2001-151283, and the like.
Examples of the electric dispenser container include: the container is provided with a member for automatically ejecting a predetermined amount of content by placing a hand on the sensor.
In this specification, one ejection operation of the quantitative ejection container is defined as follows.
When the quantitative discharge container is a stroke-type push-type container, the one discharge operation is an operation of pushing the container once in a full stroke. The "full stroke" as referred to herein means a state in which a load of 7kg is applied for 3 seconds through a stroke.
When the quantitative discharge container is a squeeze-type push container, the primary discharge operation is an operation of pushing and deforming the push portion of the container by one push. The term "press deformation" as used herein refers to a state in which a load of 7kg is applied by pressing for 3 seconds. The pressing portion of the container is different depending on the shape of the container, and refers to, for example, a side outer peripheral portion of the container.
In the case where the quantitative discharge container is an electric dispenser, the one discharge operation is an operation of placing a hand on a sensing portion that controls discharge of the content of the container, for example.
The volume of the quantitative discharge container for multiple discharge is not particularly limited, but is usually in the range of 5mL to 2,000mL from the viewpoint of storing the external skin preparation composition.
< composition of external preparation for skin >)
The composition for external use for skin (hereinafter, also referred to as the composition for external use for skin of the present invention or the composition of the present invention) is a composition containing 1 or more acids selected from lactic acid, pyruvic acid and urocanic acid or a salt thereof (a). The composition is contained in the quantitative discharge container and is discharged from the quantitative discharge container for use.
(component (A))
The component (A) is at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or a salt thereof. Component (a) functions as a bactericidal or virucidal component.
Examples of salts of lactic acid, pyruvic acid and urocanic acid include: alkali metal salts such as potassium salt and sodium salt of lactic acid or pyruvic acid; alkaline earth metal salts such as calcium salts and magnesium salts; an amine salt; ammonium salts, and the like. Among these, from the viewpoint of improving sterilization or virucidal properties and the ease of acquisition, 1 or more selected from alkali metal salts and alkaline earth metal salts of lactic acid, pyruvic acid and urocanic acid is preferable, 1 or more selected from potassium salt, sodium salt and calcium salt is more preferable, and 1 or more selected from potassium lactate, sodium lactate and calcium lactate is still more preferable.
From the viewpoint of improving sterilization or virucidal properties, the component (a) is preferably lactic acid or a salt thereof, more preferably 1 or more selected from lactic acid, potassium lactate, sodium lactate, and calcium lactate, and even more preferably contains lactic acid.
When the component (a) contains lactic acid, the content of lactic acid or a salt thereof in the total amount of the component (a) is preferably 80 mass% or more, more preferably 90 mass% or more, and most preferably 100 mass% from the viewpoint of improving sterilization or virucidal activity.
The content of the component (a) in the composition of the present invention is preferably 0.05 mass% or more, more preferably 0.1 mass% or more, still more preferably 0.2 mass% or more, still more preferably 0.3 mass% or more, and still more preferably 0.5 mass% or more, from the viewpoint of improving sterilization or virucidal properties. From the viewpoint of suppressing skin irritation, the content is preferably 15% by mass or less, more preferably 10% by mass or less, further preferably 5.0% by mass or less, further more preferably 4.0% by mass or less, further more preferably 3.0% by mass or less, further more preferably 2.5% by mass or less, further more preferably 2.0% by mass or less. The content of the component (a) in the composition is preferably 0.05 mass% or more and 15 mass% or less, more preferably 0.05 mass% or more and 10 mass% or less, still more preferably 0.1 mass% or more and 10 mass% or less, still more preferably 0.2 mass% or more and 5.0 mass% or less, still more preferably 0.3 mass% or more and 4.0 mass% or less, still more preferably 0.5 mass% or more and 3.0 mass% or less, still more preferably 0.5 mass% or more and 2.5 mass% or less, and still more preferably 0.5 mass% or more and 2.0 mass% or less.
In the present specification, when the component (a) contains a salt, the "content of the component (a)" refers to the sum of the amounts of the acids ("component (A1) existing in the acid form" and "component (A2) existing in the dissociated form)") and the amount obtained by converting the amount of the salt into the amount of the dissociated form.
The content of the component (A1) in the composition of the present invention is preferably 0.02 mass% or more, more preferably 0.04 mass% or more, still more preferably 0.05 mass% or more, still more preferably 0.1 mass% or more, still more preferably 0.2 mass% or more, still more preferably 0.3 mass% or more, from the viewpoint of improving sterilization or virucidal properties. From the viewpoint of suppressing skin irritation, it is preferably 10% by mass or less, more preferably 5.0% by mass or less, still more preferably 4.0% by mass or less, still more preferably 3.0% by mass or less, still more preferably 2.5% by mass or less, still more preferably 2.0% by mass or less, still more preferably 1.0% by mass or less. The content of the component (A1) in the composition of the present invention is preferably 0.02 mass% or more and 10 mass% or less, more preferably 0.04 mass% or more and 5.0 mass% or less, still more preferably 0.05 mass% or more and 4.0 mass% or less, still 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% or more and 2.0 mass% or less, and still more preferably 0.3 mass% or more and 1.0 mass% or less.
When the component (A1) is the component (A1) of the acid derived from the component (a) and the component (A2) is the component (A2) of the acid derived from the component (a) in the composition of the present invention, the content of the component (A1) in the composition of the present invention can be calculated by the following formula.
The content (mass%) of the component (A1) in the composition=the content (mass%) of the component (a) in the composition×the molar ratio [ (A1)/{ (A1) + (A2) } ] in the composition
Here, "molar ratio [ (A1)/{ (A1) + (A2) } ]" in the composition means the molar ratio of the component (A1) to the total of the component (A1) and the component (A2) present in the composition, which can be calculated by the method described in the specific examples in the present invention.
From the viewpoint of improving sterilization or virucidal properties, 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 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 further preferably 0.5 or less. When the component (A1) and the component (A2) are the component (A1) and the component (A2) in the form of an acid derived from the component (a) in the composition, the molar ratio [ (A1)/{ (A1) + (A2) } ] in the composition is preferably 0.2 to 0.6, more preferably 0.3 to 0.55, still more preferably 0.4 to 0.5.
Component (B) nonionic tackifier
From the viewpoint of improving the feel in use, the skin external agent composition may further contain a nonionic tackifier as component (B). In the present specification, "good feeling in use" means that the skin external composition has little dry feel when wet with water and good touch after being applied to skin and dried.
The component (B) used in the composition of the present invention is preferably a water-soluble nonionic thickener from the viewpoint of improving the feel of use, the viewpoint of improving or maintaining sterilization or virucidal properties, and the viewpoint of improving the solubility in the composition. Specific examples of the component (B) include: cellulose ethers such as hydroxybutyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and hydroxyethyl cellulose; propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropyl guar gum, locust bean gum, amylose, hydroxyethyl amylose, starch or derivatives thereof, and the like; 1 or 2 or more of these may be used.
Among the above, the component (B) is preferably 1 or more selected from cellulose ethers and polyvinyl alcohols, more preferably 1 or more selected from hydroxybutyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, and polyvinyl alcohols, still more preferably 1 or more selected from hydroxyethyl cellulose and polyvinyl alcohols, and still more preferably hydroxyethyl cellulose, from the viewpoints of maintaining sterilization or virucidal properties and improving the feel of use of the composition.
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, still more preferably 1,500 or more, still more preferably 2,000 or more, from the viewpoint of improving the feel of the composition in use, preferably 8,000 or less, more preferably 6,000 or less, still more preferably 5,000 or less, from the viewpoint of the ejectability of the composition. The polymerization degree of the polyvinyl alcohol is preferably 500 to 8,000, more preferably 700 to 8,000, still more preferably 1,000 to 6,000, still more preferably 1,500 to 6,000, still more preferably 2,000 to 5,000.
The saponification degree of the polyvinyl alcohol is not particularly limited, but 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, from the viewpoint of improving the feel of the composition in use.
As component (B), a commercially available nonionic tackifier may be used. Examples of the hydroxyethylcellulose include "Natrosol HEC 250HHX" manufactured by Ashland Co., ltd., and "HEC Daicel 850SE" manufactured by Daicel Co., ltd.; examples of the polyvinyl alcohol include "JC-40" manufactured by JAPAN VAM & POVAL Co.
When the component (B) is used, the content of the component (B) in the composition of the present invention is preferably 0.01% by mass or more, more preferably 0.02% by mass or more, still more preferably 0.05% by mass or more, still more preferably 0.1% by mass or more, still more preferably 0.2% by mass or more, from the viewpoint of improving the feel of the composition in use, preferably 20% by mass or less, more preferably 15% by mass or less, still more preferably 10% by mass or less, still more preferably 5% by mass or less, still more preferably 3% by mass or less, still more preferably 1% by mass or less, and still more preferably 0.5% by mass or less, from the viewpoint of improving the ejection property of the composition of the present invention and improving or maintaining the bactericidal or antiviral properties. The content of the 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, still more preferably 0.05% by mass or more and 15% by mass or less, still 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, still more preferably 0.2% by mass or more and 1% by mass or less, still more preferably 0.2% by mass or more and 0.5% by mass or less.
(Water)
The composition for external use for skin of the present invention preferably further contains water from the viewpoint of dissolving the component (a) and improving the ejection property of the composition. 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, still more preferably 85% by mass or more, still more preferably 90% by mass or more, still more preferably 95% by mass or more, and still more preferably 99.95% by mass or less, from the viewpoint of dissolving the component (a) and improving the ejection property.
The total content of the component (a) and water in the skin external agent 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, still more preferably 85% by mass or more, still more preferably 90% by mass or more, still more preferably 95% by mass or more, and still more preferably 100% by mass or less, from the viewpoint of obtaining the effect of the present invention, the solubility of the component (a), and the improvement of the ejection property.
(polyol)
The composition for external use for skin of the present invention may further contain a polyhydric alcohol from the viewpoint of making the polarity of the composition close to the polarity of the skin surface and easily spreading on the skin and uniformly developing the bactericidal or virucidal component on the target coating surface.
As the polyol, a polyol having a logPow value satisfying-2.0 or more as an octanol/water partition coefficient can be preferably used. A higher logPow value indicates a higher hydrophobicity, and it is expected that the composition is more easily affinitized to the skin than pure water by hydrophobizing the composition by containing a specific amount of the polyhydric alcohol in the composition.
Here the number of the elements to be processed is,
pow is the concentration ratio of the polyhydric alcohol in the 2 solvent phases when the polyhydric alcohol is added to the 2 solvent phases of 1-octanol and water and brought to an equilibrium state,
log pow=log10 (concentration of polyol in 1-octanol phase/concentration of polyol in water phase).
The logPow value of the polyol can be calculated using the algorithm "XLOGP3" described in Renxiao Wang et al, j.chem. Inf. Model.2007, vol.47, pp.2140.
Specific examples of the polyol include: straight-chain diols such as propylene glycol (1, 2-propanediol), 1, 3-propanediol, dipropylene glycol, 1, 2-butanediol, 1, 3-butanediol, 1, 4-butanediol, 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-dodecanediol, 1, 12-dodecanediol, 1, 2-tetradecanediol, 1, 2-hexadecanediol, and 1, 16-hexadecanediol;
Linear triols such as 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, and 1,2, 10-decanetriol;
branched diols or triols such as 2-methyl-1, 3-propanediol, 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 ether, 3,7,11, 15-tetramethylhexadecane-1, 2, 3-triol; and
And polymers such as polyethylene glycol, polyglycerol, PPG-10 butanediol.
1 or 2 or more of these may be used.
When the skin external composition of the present invention contains a polyhydric alcohol, the content of the polyhydric alcohol in the skin external composition 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, still more preferably 1.5% by mass or more, still more preferably 2.0% by mass or more, from the viewpoint of facilitating spreading on the skin and enabling the bactericidal or virucidal component to be uniformly exerted on the target spreading surface, and from the viewpoint of reducing the sticky feeling upon spreading, it is preferably 50% by mass or less, more preferably 30% by mass or less, and still more preferably 20% by mass or less. The content of the polyhydric alcohol in the skin external agent 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, still more preferably 0.5% by mass or more and 30% by mass or less, still more preferably 1.0% by mass or more and 30% by mass or less, still 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 adjustor)
The skin external composition of the present invention preferably contains a pH adjuster from the viewpoint of adjusting the pH to a preferred range.
As the pH adjuster, an acid component, an alkali component, a buffer component, or the like can be used as long as it is a component capable of adjusting the pH of the composition to a desired range. Among these, from the viewpoint of bringing the pH of the composition containing the component (a) to the following range (preferably 3.5 or more) at 25 ℃, it is preferable to use at least an alkaline component as the pH adjuster.
As the alkaline component, either an organic alkaline agent or an inorganic alkaline agent may be used, but from the viewpoints of solubility in water, ease of acquisition and economy, an inorganic alkaline agent is preferable.
Examples of the inorganic alkaline agent include: metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide; metal carbonates such as sodium carbonate and sodium hydrogencarbonate; 1 or 2 or more of these may be used. Among these, from the viewpoints of ease of acquisition and economy, 1 or more selected from the group consisting of alkali metal hydroxides and alkaline earth metal hydroxides is preferable, more preferable is alkali metal hydroxide, still more preferable is 1 or more selected from the group consisting of sodium hydroxide and potassium hydroxide, and still more preferable is sodium hydroxide.
In the case where the skin external composition contains a pH adjuster, the content of the pH adjuster in the composition may be such that the pH of the composition can be adjusted to a desired range.
(Metal ion concentration)
In the present invention, it is preferable to increase the content of the component (a) in the skin external composition of the present invention from the viewpoint of increasing the content of the component (A1) in the skin external composition of the present invention. Further, in the case where the content of the component (a) in the skin external composition is increased, 1 or more kinds selected from the hydroxides of alkali metals and the hydroxides of alkaline earth metals may be preferably used in the skin external composition from the viewpoint of controlling the pH within the target range. The alkali metal hydroxide and the alkaline earth metal hydroxide are as described above.
As a result of using 1 or more kinds selected from the alkali metal hydroxide and alkaline earth metal hydroxide, the metal ion concentration in the skin external preparation composition is preferably 0.002mol/L or more, more preferably 0.005mol/L or more, still more preferably 0.01mol/L or more, still more preferably 0.02mol/L or more. On the other hand, from the viewpoint of maintaining the mineral balance of the skin, the metal ion concentration in the skin external agent composition is preferably 0.80mol/L or less, more preferably 0.50mol/L or less, still more preferably 0.30mol/L or less, and still more preferably 0.20mol/L or less. The concentration of the metal ion in the skin external composition is preferably 0.002mol/L or more and 0.80mol/L or less, more preferably 0.002mol/L or more and 0.50mol/L or less, still more preferably 0.005mol/L or more and 0.50mol/L or less, still more preferably 0.01mol/L or more and 0.30mol/L or less, still more preferably 0.02mol/L or more and 0.20mol/L or less.
In the present specification, the "concentration of metal ions in the skin external composition" refers to the concentration of all metal ions present in the composition. In the composition used in the present invention, the metal ions derived from the specific organic acid salt contained in the component (a) and the total concentration of the metal ions derived from the pH adjuster are mainly used.
In general, if metal ions are present in the composition, the bactericidal effect of a bactericidal agent such as benzalkonium chloride tends to be suppressed. However, in the skin external composition used in the present invention, the bactericidal or virucidal activity due to the component (a) is not inhibited by metal ions, and thus excellent bactericidal or virucidal activity can be exhibited.
The concentration of metal ions in the composition can be determined by ion selective electrode methods.
(other Components)
In addition to the above components, the skin external composition of the present invention may contain other components as needed, for example, surfactants, ultraviolet absorbers, antioxidants, preservatives, antiperspirants, fragrances, moisturizers, feel modifiers, anti-inflammatory agents, and the like.
The composition for external use for skin according to the present invention is a composition in which component (a) is used as a bactericidal or virucidal component, and from this viewpoint, it is possible to exhibit bactericidal or virucidal properties even if a monohydric alcohol having 4 or less carbon atoms such as ethanol or isopropanol is not blended. Further, from the viewpoint of suppressing skin irritation, the content of monohydric alcohol having 4 or less carbon atoms in the composition is preferably 60% by mass or less, more preferably 50% by mass or less, 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 0.05% by mass or less, still more preferably less than 0.01% by mass, and most preferably substantially 0% by mass.
Component (C) an organic acid or a salt thereof other than component (A)
From the viewpoint that the composition for external use for skin is a composition using the component (a) as a bactericidal or virucidal component, the composition can exhibit bactericidal or virucidal properties even without blending an organic acid or a salt thereof other than the component (a) (hereinafter also referred to as "component (C)"). From this viewpoint and from the viewpoint 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, further preferably 5% by mass or less, further more preferably 3% by mass or less, further more preferably 1% by mass or less, further more preferably 0.5% by mass or less, further more preferably less than 0.5% by mass, further more preferably less than 0.1% by mass, and most preferably substantially 0% by mass.
In the present specification, when the component (C) is an organic acid salt, the "content of the component (C)" means an amount converted into the organic acid.
In addition, from the viewpoint of maintaining sterilization or virucidal properties and suppressing skin irritation, the mass ratio [ (C)/(a) ] of the organic acid or salt thereof (C) other than the component (a) to the component (a) in the external skin preparation composition is preferably less than 1, more preferably 0.8 or less, still more preferably 0.6 or less, still 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, still more preferably 0.05 or less, still more preferably 0.01 or less, and still more preferably substantially 0.
Examples of the organic acid or a salt thereof other than the component (a) corresponding to the component (C) include carboxylic acid compounds, sulfonic acid compounds, or salts thereof other than the component (a).
Examples of the carboxylic acid compound or a salt thereof include: aliphatic monocarboxylic acids having 4 or less carbon atoms such as acetic acid, propionic acid and butyric acid; aromatic monocarboxylic acids such as benzoic acid; aliphatic dicarboxylic acids such as malonic acid, succinic acid, glutaric acid, adipic acid, maleic acid, fumaric acid, and the like; aromatic dicarboxylic acids such as phthalic acid and isophthalic acid; polycarboxylic acids such as polyglutamic acid; hydroxycarboxylic acids such as malic acid, glycolic acid, hydroxyacrylic acid, glyceric acid, tartaric acid, and citric acid; acidic amino acids such as glutamic acid and aspartic acid; pyrrolidone carboxylic acid; or salts of these.
The sulfonic acid compound or a salt thereof may be: aliphatic sulfonic acids such as methanesulfonic acid and ethanesulfonic acid; aromatic sulfonic acids such as p-toluenesulfonic acid and naphthalenesulfonic acid; or salts of these.
Examples of the salt of the organic acid include: alkali metal salts such as potassium salt and sodium salt; alkaline earth metal salts such as calcium salts and magnesium salts; an amine salt; ammonium salts, and the like.
From the viewpoint that the skin external composition is a composition using the component (a) as a bactericidal or virucidal component, even if the following bactericides are not formulated, for example: quaternary ammonium salts such as benzalkonium chloride and benzethonium chloride; amphoteric surfactants such as alkyldiaminoethylglycine and alkylpolyaminoethylglycine; biguanides such as chlorhexidine gluconate; sodium hypochlorite; aldehydes such as glutaraldehyde, phthalaldehyde, formalin, etc.; povidone iodine; iodine tincture; phenol; cresol soap solution; peracetic acid; hydroxyl alcohols (oxydol) and the like can also exhibit bactericidal or virucidal properties. From this viewpoint and from the viewpoint of suppressing skin irritation, the content of the bactericide in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, still more preferably 5% by mass or less, still more preferably 3% by mass or less, still more preferably 1% by mass or less, still more preferably 0.07% by mass or less, still more preferably 0.05% by mass or less, still more preferably 0.03% by mass or less, still more preferably less than 0.01% by mass, and most preferably substantially 0% by mass. On the other hand, in the case of blending the above-mentioned bactericide, the content of the bactericide in the composition is preferably 0.01 mass% or more, more preferably 0.05 mass% or more, from the viewpoint of improving sterilization or virucidal properties.
From the viewpoint of suppressing skin irritation, the mass ratio of the bactericide to the component (a) (bactericide/component (a)) is preferably 0.5 or less, more preferably 0.2 or less, further preferably 0.1 or less, further more preferably 0.05 or less, further more preferably 0.03 or less, further more preferably 0.01 or less, and most preferably substantially 0. On the other hand, in the case of blending the above-mentioned bactericide, the mass ratio of the above-mentioned bactericide to the component (a) (bactericide/component (a)) is preferably 0.01 or more, more preferably 0.05 or more, from the viewpoint of improving the sterilization or virucidal effect.
In the present specification, an agent which is the above-mentioned bactericide and can also function as a surfactant is defined as a bactericide.
(viscosity)
The viscosity of the external skin preparation composition at 25 ℃ is preferably 1.0mpa·s or more, more preferably 2.0mpa·s or more, further preferably 3.0mpa·s or more, from the viewpoint of making the ejection amount uniform in each ejection operation from the quantitative ejection container, and from the viewpoint of improving the application property to the skin, preferably 30,000mpa·s or less, more preferably 25,000mpa·s or less, further preferably 10,000mpa·s or less, further more preferably 8,000mpa·s or less, further more preferably 6,500mpa·s or less, further more preferably 5,000mpa·s or less, further more preferably 2,000mpa·s or less, further more preferably 1,000mpa·s or less, further more preferably 700mpa·s or less, from the viewpoint of improving the ejection property by the quantitative ejection container, and from the viewpoint of improving or maintaining sterilization or virucidal property.
The lower the viscosity of the external skin preparation composition, the more difficult it is to control the amount of the external skin preparation composition to be supplied to the skin, but the external skin preparation of the present invention is advantageous in that a fixed amount can be discharged and supplied to the skin even with a composition having a low viscosity.
When the quantitative discharge container for storing the composition is a stroke-type and pump-type push-type container, the viscosity of the composition at 25 ℃ is more preferably 10,000mpa·s or less, still more preferably 8,000mpa·s or less, still more preferably 6,500mpa·s or less, still more preferably 5,000mpa·s or less, still more preferably 2,000mpa·s or less, still more preferably 1,000mpa·s or less, and still more preferably 700mpa·s or less, from the viewpoint of improving the discharge property and the ease of application at the time of application. In addition, from the viewpoint of preventing liquid dripping during ejection and the viewpoint of preventing spillage during application, it may be 5.0mpa·s or more, and further 100mpa·s or more.
When the quantitative discharge container for storing the composition is a stroke-type and spray-type push-type container, the viscosity of the composition at 25 ℃ is more preferably 1,000mpa·s or less, still more preferably 800mpa·s or less, still more preferably 500mpa·s or less, still more preferably 300mpa·s or less, still more preferably 200mpa·s or less, still more preferably 100mpa·s or less, from the viewpoint of improving the discharge property and the ease of application at the time of application. In addition, from the viewpoint of preventing liquid dripping during ejection and the viewpoint of preventing spillage during application, it may be 5.0mpa·s or more, and further 10.0mpa·s or more.
When the quantitative discharge container for storing the composition is a squeeze-type squeeze container, the viscosity of the composition at 25 ℃ is more preferably 25,000mpa·s or less, still more preferably 10,000mpa·s or less, still more preferably 8,000mpa·s or less, still more preferably 6,500mpa·s or less, still more preferably 2,000mpa·s or less, and still more preferably 100mpa·s or more, still more preferably 500mpa·s or more, from the same viewpoint of quantitative discharge property.
When the quantitative discharge container for storing the composition is an electric dispenser container, the viscosity of the composition at 25 ℃ is more preferably 1,000mpa·s or less, still more preferably 800mpa·s or less, still more preferably 500mpa·s or less, still more preferably 300mpa·s or less, still more preferably 200mpa·s or less, still more preferably 100mpa·s or less, from the viewpoint of the discharge property. In addition, from the viewpoint of preventing liquid dripping during ejection and the viewpoint of preventing spillage during application, it may be 5.0mpa·s or more, and further 10.0mpa·s or more.
The viscosity of the composition at 25℃can be measured by the method described in the examples.
(pH value)
From the viewpoint of adjusting the content ratio of the component (A1) in the composition of the present invention and the viewpoint of suppressing skin irritation, the pH of the skin external composition at 25 ℃ is preferably 3.5 or more, more preferably 3.7 or more. In addition, from the viewpoint of improving sterilization or virucidal performance, it is preferably 5.0 or less, more preferably 4.5 or less. The pH of the skin external composition at 25 ℃ is preferably 3.5 to 5.0, more preferably 3.5 to 4.5, and even more preferably 3.7 to 4.5.
The pH of the composition at 25 ℃ can be measured by the method described in the examples.
< morphology of skin external preparation composition >)
The composition for external use for skin according to the present invention may have fluidity at 25 ℃. The form is not particularly limited, and may be, for example, liquid, gel, cream, or foam. The liquid is preferable from the viewpoint of easy spreading on the skin and uniform exertion of the bactericidal or virucidal component on the target coating surface. In addition, from the viewpoint of preventing dripping from the skin when applied to the skin and supplying the component (A1) to the skin at a target amount, it is preferably in the form of a gel, a cream or a foam.
Further, 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. The oil-in-water emulsion composition is preferable from the viewpoint of easy spreading on the skin and uniform exertion of the bactericidal or virucidal component on the target coating surface. In addition, from the viewpoint of preventing dripping from the skin when applied to the skin and supplying the component (A1) in a target amount, a water-in-oil emulsion composition is preferable.
The external preparation for skin of the present invention is more preferably in the form of the following (I) or (II).
(I) A skin external preparation is prepared by storing a skin external preparation composition in a quantitative discharge container,
the composition contains at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or its salt (A),
when the component (A1) is the component (A1) in the acid form of the acid present in the composition, the content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg to 80mg,
the component (A) is lactic acid or a salt thereof,
the mass ratio [ (C)/(A) ] of the organic acid or its salt (C) other than the component (A) to the component (A) in the composition is less than 1,
The pH of the composition at 25deg.C is 3.5-5.0.
(II) an external preparation for skin comprising a composition for external use contained in a quantitative discharge container,
the composition contains at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or its salt (A),
when the component (A1) is the component (A1) in the acid form of the acid present in the composition, the content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg to 80mg,
the composition further comprises a nonionic tackifier (B),
the viscosity of the composition is 100 mPas to 10,000 mPas at 25 ℃.
The external preparation for skin having the form of (I) has the above composition, and thus has a remarkable effect of improving the sterilization or virucidal effect.
The mass ratio [ (C)/(a) ] of the organic acid or salt (C) other than the component (a) to the component (a) in the composition for external use for skin in the external use agent for skin in the form of the above (I) is less than 1, preferably 0.8 or less, more preferably 0.6 or less, still 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, still more preferably 0.05 or less, still more preferably 0.01 or less, and still more preferably substantially 0.
The pH of the skin external preparation composition used in the skin external preparation of the above-described form (I) is 3.5 to 5.0, preferably 3.5 to 4.5, more preferably 3.7 to 4.5 at 25 ℃.
Other important conditions and preferable ranges thereof are the same as those described above.
The external preparation for skin having the above-described form (II) can achieve both sterilization or virucidal effects and a better feeling of use.
The viscosity of the skin external preparation composition used for the skin external preparation in the form of the above (II) is 100 to 10,000mpa·s, preferably 100 to 5,000mpa·s, more preferably 100 to 8,000mpa·s, still more preferably 100 to 2,000mpa·s, still more preferably 100 to 1,000mpa·s, still more preferably 100 to 800mpa·s, still more preferably 100 to 700mpa·s, at 25 ℃.
Other important conditions and preferred ranges thereof are the same as those described above.
< morphology of skin external preparation >
The external skin preparation of the present invention causes the component (a) as a bactericidal or virucidal component contained in the discharged composition to remain on the skin surface, thereby exhibiting bactericidal or virucidal properties on the skin surface. From the viewpoint of obtaining this effect, the skin external preparation of the present invention is preferably a leave-on skin external preparation. That is, when the external skin preparation of the present invention is used, the composition discharged from the quantitative discharge container is applied to the skin by coating or the like, and then the composition is used while being left on the skin surface without being removed by washing with water or the like.
The external skin preparation of the present invention is more preferably a finger leave-on external skin preparation from the viewpoint of preventing contact infection caused by bacteria or viruses.
< bacteria or viruses to be the object of exhibiting sterilizing or virucidal >)
The bacteria or viruses to be sterilized or virucidal target of the skin external preparation of the present invention are not particularly limited as long as they are inactivated or killed by contact with an acid, and for example, microorganisms described in the rule of countermeasure against infectious diseases in nursing department of the Ministry of labor of thicknesswise can be used.
Specifically, bacteria include: anthrax, tuberculosis, hemolytic streptococcus, staphylococcus aureus, pneumococcus, etc. as gram positive bacteria; or Rabbit bacteria, plague bacteria, brucella, meliter bacteria, vibrio cholerae, salmonella, dysentery bacteria, intestinal hemorrhagic Escherichia coli, pertussis bacteria, etc. as gram negative bacteria. In addition, viruses include: arenaviruses, ebola viruses, poxviruses, endoviruses, marburg viruses, coronaviruses, monkey poxviruses, coronaviruses, influenza viruses, RS viruses, herpesviruses, mumps viruses, varicella zoster viruses, rubella viruses, measles viruses, and the like as envelope viruses; enteroviruses, adenoviruses, coxsackieviruses, noroviruses, rotaviruses, and the like, as non-enveloped viruses.
In this example, serratia bacteria was exemplified for the evaluation of sterilization and virucidal activity, but the bacteria and viruses to be treated in the present invention are not limited thereto.
[ method of supplying component (A) to the application site of the skin surface ]
The present invention also provides a method for supplying at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or a salt (a) thereof to an application site on the skin surface, comprising the following steps (I) and (II) in this order (hereinafter, also referred to simply as "method of the present invention").
Step (I): and cleaning the application part.
Step (II): and a step of discharging the composition from a quantitative discharge container containing the composition containing the component (A) by a single discharge operation and supplying the composition to the application site, wherein when the component (A1) in the acid form in the acid present in the composition is (A1), the content of the component (A1) in the composition discharged from the quantitative discharge container by a single discharge operation is 0.05mg or more and 80mg or less.
According to the method of the present invention, excellent sterilization or virucidal activity can be exhibited on the skin surface, and skin irritation can be suppressed. The preferable modes of the component (A), the composition containing the component (A), the quantitative discharge container, and these are the same as those described above.
In step (I), the application site of the skin surface is first cleaned using water, soap, shower gel, hand wash, etc. Since components such as lactic acid which are naturally present in the skin after cleansing are washed out and the defenses against bacteria or viruses present in the outside are reduced, it is preferable to apply the above composition in the step (II) after the step (I) is performed to carry out the method of the present invention.
After cleaning in step (I), step (II) may be performed after drying the applied portion of the skin surface by air drying or the like.
In step (II), a composition containing the above component (a) is ejected onto the application site of the skin surface that has been cleaned in step (I). The content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg or more, preferably 0.1mg or more, more preferably 0.2mg or more, still more preferably 0.4mg or more, still more preferably 0.5mg or more, still more preferably 1.0mg or more, still more preferably 2.0mg or more, and from the viewpoint of suppressing skin irritation, 80mg or less, preferably 60mg or less, still more preferably 50mg or less, and still more preferably 45mg or less. The content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg or more and 80mg or less, preferably 0.1mg or more and 60mg or less, more preferably 0.2mg or more and 60mg or less, still more preferably 0.4mg or more and 50mg or less, still more preferably 0.5mg or more and 50mg or less, still more preferably 1.0mg or more and 45mg or less, and still more preferably 2.0mg or more and 45mg or less.
The content of the component (A1) in the composition discharged by one discharge operation can be determined by the same method as described above.
Preferably, after the composition is applied to the skin in step (II), the composition is left on the skin surface without being removed by washing with water or the like. The reason for this is that: the composition can be used as a leave-on preparation, and can impart sterilization or virucidal properties to the skin surface by leaving the component (a) as a sterilizing or virucidal component on the skin surface.
With respect to the above embodiments, the present invention further discloses the following.
<1>
A skin external preparation is prepared by storing a skin external preparation composition in a quantitative discharge container,
the composition contains at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or its salt (A),
when the component (A1) is the component (A1) in the acid form of the acid present in the composition, the content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg to 80 mg.
<2>
The external preparation for skin as described in < 1 >, wherein the content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is preferably 0.1mg or more and 60mg or less, more preferably 0.2mg or more and 60mg or less, still more preferably 0.4mg or more and 50mg or less, still more preferably 0.5mg or more and 50mg or less, still more preferably 1.0mg or more and 45mg or less, still more preferably 2.0mg or more and 45mg or less.
<3>
The external preparation for skin according to claim 1 or 2, wherein the amount of the composition discharged from the quantitative discharge container by one discharge operation is preferably 0.05g or more and 3.0g or less, more preferably 0.1g or more and 2.5g or less, and still more preferably 0.2g or more and 2.0g or less.
<4>
The external preparation for skin according to any one of < 1 > to < 3 >, wherein the component (A) contains lactic acid or a salt thereof, preferably 1 or more selected from lactic acid, potassium lactate, sodium lactate, and calcium lactate, more preferably lactic acid.
<5>
The external preparation for skin according to any one of < 1 > to < 4 >, wherein the component (A) contains lactic acid, and the content of lactic acid or a salt thereof in the total amount of the component (A) is preferably 80% by mass or more, more preferably 90% by mass or more, and most preferably 100% by mass.
<6>
The external preparation for skin according to any one of < 1 > to < 5 >, wherein the content of the component (a) in the composition is preferably 0.05 mass% or more and 15 mass% or less, more preferably 0.05 mass% or more and 10 mass% or less, still more preferably 0.1 mass% or more and 10 mass% or less, still more preferably 0.2 mass% or more and 5.0 mass% or less, still more preferably 0.3 mass% or more and 4.0 mass% or less, still more preferably 0.5 mass% or more and 3.0 mass% or less, still more preferably 0.5 mass% or more and 2.5 mass% or less, still more preferably 0.5 mass% or more and 2.0 mass% or less.
<7>
The external preparation for skin according to any one of < 1 > to < 6 >, wherein the content of the component (A1) in the composition is preferably 0.02 mass% or more and 10 mass% or less, more preferably 0.04 mass% or more and 5.0 mass% or less, still more preferably 0.05 mass% or more and 4.0 mass% or less, still 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% or more and 2.0 mass% or less, and still more preferably 0.3 mass% or more and 1.0 mass% or less.
<8>
The external preparation for skin according to any one of < 1 > to < 7 >, wherein the molar ratio [ (A1)/{ (A1) + (A2) } ] in the composition is preferably 0.2 to 0.6, more preferably 0.3 to 0.55, still more preferably 0.4 to 0.5, when the component in the acid form of the acid derived from the component (A) present in the composition is the component (A1) and the component in the dissociated form is the component (A2).
<9>
The external preparation for skin according to any one of < 1 > to < 8 >, wherein the above composition further contains a nonionic tackifier as component (B).
<10>
The external skin preparation according to claim < 9 > wherein the component (B) is a water-soluble nonionic thickener, preferably 1 or 2 or more selected from the group consisting of cellulose ethers, propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropyl guar gum, locust bean gum, amylose, hydroxyethyl amylose, starch and derivatives thereof, more preferably 1 or more selected from the group consisting of cellulose ethers and polyvinyl alcohol, still more preferably 1 or more selected from the group consisting of hydroxybutyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose and polyvinyl alcohol, still more preferably 1 or more selected from the group consisting of hydroxyethyl cellulose and polyvinyl alcohol, and still more preferably hydroxyethyl cellulose.
<11>
The external preparation for skin according to claim < 10 > wherein the polyvinyl alcohol has a polymerization degree of preferably 500 to 8,000, more preferably 700 to 8,000, still more preferably 1,000 to 6,000, still more preferably 1,500 to 6,000, still more preferably 2,000 to 5,000.
<12>
The external preparation for skin according to claim < 10 > or < 11 >, wherein 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.
<13>
The external preparation for skin according to any one of < 9 > to < 12 >, wherein the content of the component (B) in the composition is preferably 0.01 mass% or more and 20 mass% or less, more preferably 0.02 mass% or more and 15 mass% or less, still more preferably 0.05 mass% or more and 15 mass% or less, still more preferably 0.1 mass% or more and 10 mass% or less, still more preferably 0.2 mass% or more and 5 mass% or less, still more preferably 0.2 mass% or more and 3 mass% or less, still more preferably 0.2 mass% or more and 1 mass% or less, and still more preferably 0.2 mass% or more and 0.5 mass% or less.
<14>
The external preparation for skin according to any one of < 1 > to < 13 >, wherein the composition further contains water, and the content of water in the composition is preferably 40% by mass or more, more preferably 70% by mass or more, further preferably 80% by mass or more, further more preferably 85% by mass or more, further more preferably 90% by mass or more, further more preferably 95% by mass or more, and further preferably 99.95% by mass or less.
<15>
The external preparation for skin according to any one of < 1 > to < 14 >, wherein 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, further preferably 80% by mass or more, further more preferably 85% by mass or more, further more preferably 90% by mass or more, further more preferably 95% by mass or more, and further 100% by mass or less.
<16>
The external preparation for skin according to any one of < 1 > to < 15 >, wherein the above composition further contains a polyhydric alcohol.
<17>
The external preparation for skin according to claim 16, wherein the polyhydric alcohol has a logPow value as octanol/water partition coefficient of-2.0 or more.
<18>
The external preparation for skin according to < 16 > or < 17 >, wherein, the polyhydric alcohol is selected from propylene glycol (1, 2-propylene glycol), 1, 3-propylene glycol, dipropylene glycol, 1, 2-butanediol, 1, 3-butanediol, 1, 4-butanediol, 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-dodecanediol, 1, 12-dodecanediol, 1, 2-tetradecanediol, 1, 2-hexadecanediol, 1, 16-hexadecanediol, glycerol 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-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 ether, 3,7,11, 15-tetramethylhexadecane-1, 2, 3-triol, polyethylene glycol, more than 1 kind of polyglycerol and PPG-10 butanediol.
<19>
The external preparation for skin according to any one of < 16 > to < 18 >, wherein the content of the polyhydric alcohol 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, still more preferably 0.5% by mass or more and 30% by mass or less, still more preferably 1.0% by mass or more and 30% by mass or less, still 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.
<20>
The external preparation for skin according to any one of < 1 > to < 19 >, wherein the composition contains a pH adjustor, preferably an inorganic alkaline agent, more preferably 1 or more selected from the group consisting of alkali metal hydroxides and alkaline earth metal hydroxides, further preferably an alkali metal hydroxide, further more preferably 1 or more selected from the group consisting of sodium hydroxide and potassium hydroxide, and further more preferably sodium hydroxide.
<21>
The external preparation for skin according to any one of < 1 > to < 20 >, wherein the concentration of the metal ion in the composition is preferably 0.002mol/L or more and 0.80mol/L or less, more preferably 0.002mol/L or more and 0.50mol/L or less, still more preferably 0.005mol/L or more and 0.50mol/L or less, still more preferably 0.01mol/L or more and 0.30mol/L or less, still more preferably 0.02mol/L or more and 0.20mol/L or less.
<22>
The external preparation for skin according to any one of < 1 > to < 21 >, wherein the content of the monohydric alcohol having 4 or less carbon atoms in the composition is preferably 60% by mass or less, more preferably 50% by mass or less, further preferably 40% by mass or less, further more preferably 30% by mass or less, further more preferably 10% by mass or less, further more preferably 5.0% by mass or less, further more preferably 1.0% by mass or less, further more preferably 0.05% by mass or less, further more preferably less than 0.01% by mass, and most preferably substantially 0% by mass.
<23>
The external preparation for skin according to any one of < 1 > to < 22 >, wherein 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, further preferably 5% by mass or less, further more preferably 3% by mass or less, further more preferably 1% by mass or less, further more preferably 0.5% by mass or less, further more preferably less than 0.5% by mass, further more preferably less than 0.1% by mass, and most preferably substantially 0% by mass.
<24>
The external preparation for skin according to claim < 23 > wherein the mass ratio [ (C)/(A) ] of the organic acid or its salt (C) other than the component (A) to the component (A) in the composition is preferably less than 1, more preferably 0.8 or less, still more preferably 0.6 or less, still 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, still more preferably 0.05 or less, still more preferably 0.01 or less, and still more preferably substantially 0.
<25>
The external skin preparation according to any one of < 1 > to < 24 >, wherein the content of the bactericide in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, further preferably 5% by mass or less, further more preferably 3% by mass or less, further more preferably 1% by mass or less, further more preferably 0.07% by mass or less, further more preferably 0.05% by mass or less, further more preferably 0.03% by mass or less, further more preferably less than 0.01% by mass, and most preferably substantially 0% by mass.
<26>
The external preparation for skin according to any one of < 1 > to < 25 >, wherein the composition contains a bactericide, and the content of the bactericide in the composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more.
<27>
The external skin preparation according to any one of < 1 > to < 26 >, wherein the viscosity of the composition at 25 ℃ is preferably 1.0mpa·s or more, more preferably 2.0mpa·s or more, further preferably 3.0mpa·s or more, preferably 30,000mpa·s or less, more preferably 25,000mpa·s or less, further preferably 10,000mpa·s or less, further more preferably 8,000mpa·s or less, further more preferably 6,500mpa·s or less, further more preferably 5,000mpa·s or less, further more preferably 2,000mpa·s or less, further more preferably 1,000mpa·s or less, further more preferably 700mpa·s or less.
<28>
The external preparation for skin of < 27 > wherein the quantitative discharge container for containing the composition is a stroke pump type push type container, and the viscosity of the composition at 25 ℃ is more preferably 5.0 mPas or more, still more preferably 100 mPas or more.
<29>
The external preparation for skin of < 27 > wherein the quantitative discharge container for containing the composition is a stroke-type and spray-type push-type container, and the viscosity of the composition at 25 ℃ is more preferably 800mpa·s or less, still more preferably 500mpa·s or less, still more preferably 300mpa·s or less, still more preferably 200mpa·s or less, still more preferably 100mpa·s or less, still more preferably 5.0mpa·s or more, and still more preferably 10.0mpa·s or more.
<30>
The external preparation for skin of < 27 > wherein the quantitative discharge container for containing the composition is a squeeze-type container, and the viscosity of the composition at 25 ℃ is more preferably 25,000mpa·s or less, still more preferably 10,000mpa·s or less, still more preferably 8,000mpa·s or less, still more preferably 6,500mpa·s or less, still more preferably 2,000mpa·s or less, still more preferably 100mpa·s or more, and still more preferably 500mpa·s or more.
<31>
The external preparation for skin of < 27 > wherein the quantitative discharge container for containing the composition is an electric dispenser container, and the viscosity of the composition at 25 ℃ is more preferably 800mpa·s or less, more preferably 500mpa·s or less, more preferably 300mpa·s or less, more preferably 200mpa·s or less, more preferably 100mpa·s or less, more preferably 5.0mpa·s or more, more preferably 10.0mpa·s or more.
<32>
The external preparation for skin according to any one of < 1 > to < 31 >, wherein the pH of the composition at 25℃is preferably 3.5 to 5.0, more preferably 3.5 to 4.5, still more preferably 3.7 to 4.5.
<33>
The external preparation for skin according to any one of < 1 > to < 32 > which is in the form of the following (I) or (II):
(I) A skin external preparation is prepared by storing a skin external preparation composition in a quantitative discharge container,
the composition contains at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or its salt (A),
when the component (A1) is the component (A1) in the acid form of the acid present in the composition, the content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg to 80mg,
The component (A) is lactic acid or a salt thereof,
the mass ratio [ (C)/(A) ] of the organic acid or its salt (C) other than the component (A) to the component (A) in the composition is less than 1,
the pH value of the composition at 25 ℃ is 3.5-5.0;
(II) an external preparation for skin comprising a composition for external use contained in a quantitative discharge container,
the composition contains at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or its salt (A),
when the component (A1) is the component (A1) in the acid form of the acid present in the composition, the content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg to 80mg,
the above composition further comprises a nonionic tackifier (B),
the viscosity of the composition is 100 mPas to 10,000 mPas at 25 ℃.
<34>
The skin external preparation according to the aspect (II) has a viscosity of preferably 100 to 5,000 mPas, more preferably 100 to 8,000 mPas, still more preferably 100 to 2,000 mPas, still more preferably 100 to 1,000 mPas, still more preferably 100 to 800 mPas, and still more preferably 100 to 700 mPas at 25 ℃.
<35>
The external preparation for skin according to any one of < 1 > to < 34 >, wherein the composition is in the form of a 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 external skin preparation, preferably a leave-on external skin preparation for fingers.
<37>
A skin external product is prepared by storing a skin external agent composition in a quantitative discharge container,
the composition contains at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or its salt (A),
when the component (A1) is the component (A1) in the acid form of the acid present in the composition, the content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg to 80 mg.
<38>
A method for supplying at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or a salt (A) thereof to an application site on the skin surface, comprising the following steps (I) and (II) in this order:
step (I): cleaning the application part;
step (II): and a step of discharging the composition from a quantitative discharge container containing the composition containing the component (A) by a single discharge operation, and supplying the composition to the application site, wherein when the component (A1) in the acid form in the acid present in the composition is (A1), the content of the component (A1) in the composition discharged from the quantitative discharge container by a single discharge operation is 0.05mg to 80 mg.
Examples
The present invention will be described below by way of examples, but the present invention is not limited to the scope of the examples. In this example, various measurements and evaluations were performed by the following methods.
(sodium ion concentration)
The sodium ion concentration of the skin external preparation composition was determined based on the amount of the pH adjustor (1 mol/L aqueous sodium hydroxide solution).
The metal ions contained in the compositions of the present examples and comparative examples were regarded as sodium ions only.
(viscosity)
The viscosity of the skin external composition was measured 3 times at 25℃using a vibration viscometer (manufactured by SEKONIC Co., ltd. "VM-10 AL"), and the average value was obtained.
The measurement conditions corresponding to the viscosity of the object are as follows:
viscosity: 1 to 100 mPas
Clamp M1, rotation speed 60rpm
A viscosity of more than 100 mPas and less than 1,000 mPas
Clamp M2, rotation speed 30rpm
A viscosity of more than 1,000 mPas and less than 10,000 mPas
Clamp M3, rotation speed 12rpm
A viscosity of more than 10,000 mPas and less than 100,000 mPas
Clamp M4 and rotating speed of 6rpm
(pH value)
The pH of the skin external composition was measured at 25℃using electrodes 6367-10D (horiba, manufactured by horiba corporation).
(content of component (A1) in the skin external composition)
When the component in the acid form of the acid derived from the component (a) present in the composition is the component (A1) and the component in the dissociated form is the component (A2), the content (mass%) of the component (A1) in the external skin preparation composition is determined according to the following calculation formula.
The content (mass%) of component (A1) in the skin external composition=the content (mass%) of component (a) in the composition× { the molar ratio [ (A1)/{ (A1) + (A2) in the composition) ] }
The content (mg) of the component (A1) in the discharged composition was determined according to the following calculation formula.
Content (mg) of component (A1) in the ejected composition=mass (g) of the composition×1000×content (mass%) of component (a) in the composition× { molar ratio [ (A1)/{ (A1) + (A2) in the composition) ] ∈ } 100
Here, the "molar ratio in composition [ (A1)/{ (A1) + (A2) was determined by the following calculation]". In the following description of the present invention,the molar amount of component (A1) is referred to as "HA", and the molar amount of component (A2) is referred to as "A - ”。
ph=pka+log (a - /HA)
log(A - HA) =ph-pKa
A - /HA=10 (pH value-pKa)
A - =10 (pH value-pKa) ×HA
According to the above, the molar ratio [ (A1)/{ (A1) + (A2) ] is
HA/(HA+A - )=HA/(HA+10 (pH value-pKa) ×HA)
=1/(1+10 (pH value-pKa) )
In the case where lactic acid is used as the component (a) (pka=3.86),
molar ratio [ lactic acid/(lactic acid+lactic acid ion)]=1/(1+10 (x-3.86) )
(x represents the pH of the composition or the pH of the skin surface).
In addition, in the case where the component (a) contains a plurality of components, in the present invention, the following calculation method is defined.
The pH of the composition was measured by the above method, and pKa of each of the plurality of components was substituted into the above formula, thereby obtaining molar ratio [ (A1)/{ (A1) + (A2) ] of each component. Then, the molar ratio [ (A1)/{ (A1) + (A2) ] among the respective components is added together, whereby the molar ratio [ (A1)/{ (A1) + (A2) ] in the case where the plurality of components (a) are used can be obtained.
Examples 1 to 12 and comparative examples 1 to 8 (preparation and evaluation of skin external preparation composition)
The components shown in tables 1 to 2 were prepared and mixed at room temperature, and then the pH values described in the tables were adjusted using 1mol/L aqueous hydrochloric acid solution and/or 1mol/L aqueous sodium hydroxide solution as a pH adjuster, to prepare skin external preparations. The blending amounts shown in tables 1 to 2 are effective component amounts (mass%) of the respective components.
After the skin external composition was contained in a quantitative discharge container, it was discharged in the amounts shown in tables 1 and 2, and the following model experiment was performed. Specifically, using piptman (manufactured by Gilson), the compositions described in tables 1 and 2 were applied to the skin surface in amounts corresponding to conditions under which both hands were fully coated by the following methods, and the in vivo bactericidal activity and skin irritation were evaluated.
In addition, "an amount corresponding to the condition of filling the palms of both hands" means that the amount (g) of the discharged composition is divided by 500cm, which is the average area of the palms of both hands 2 The amount obtained. Average area of the palms of both hands was 500cm 2 The value obtained was estimated based on the value of TPSA (total palm surface area mean palm area with fingers), which is the average value of the one-hand surface areas added as described in "Korea palm surface area database of children and alginate method estimation formula (Palm surface area data base and estimation formula in Korean children using the alginate method)" (application engineering (Applied Ergonomics), vol.42 (2011), 873-882) of Hyuk Choi et al. More specifically, the total value (cm) of the male TPSA shown in Table 2 was calculated 2 ) Total value of TPSA (cm) 2 ) The value of 2 times is taken as the average area of the palms of both hands.
(preparation of bacterial liquid)
As an in vivo (in vivo) bactericidal activity evaluation, a bacterial solution of Serratia prepared by the following method was used.
NBRC12648 strain was used as Serratia. Culturing the strain in LB (Lysogeny broth) liquid medium, centrifuging to recover the strain, and using pure water to obtain OD 600 Adjustment was performed in the manner of=10.
(in vivo sterilizing Properties: table 1)
The forearm inner of the subject was cleaned using "Biore u Rg" (manufactured by Kagaku corporation). After waiting for 5 to 10 minutes, the skin external preparation composition is discharged from the quantitative discharge container by one discharge operation, and the skin surface on the inner side of the forearm is 1cm 2 The range of (1 cm. Times.1 cm) was applied and spread in such a manner that the amount was equivalent to the conditions under which both hands were fully covered. Quantitative ejection of the type of container by one ejectionThe amounts of the skin external composition discharged by the operation are shown in table 1.
After standing for 5 minutes to dry, the Serratia solution prepared by the above method was applied to the skin surface after application of the composition in an amount (1. Mu.L/cm) 2 ). After standing for 3 minutes in this state, the applied bacterial liquid was recovered by using 2 cotton sticks. The collected bacteria were ice-cooled, whereby the reaction (action of the composition on the bacterial liquid) was stopped.
Subsequently, the number of viable bacteria was measured by the following method using a culture reader "HiTS" (manufactured by Scinics Co., ltd.), and the decrease in the number of bacteria (viable bacteria count/initial viable bacteria count) was confirmed.
Liquid culture was performed at 37℃in a culture reader "HiTS", and absorbance (turbidity) at a wavelength of 600nm was measured with time to prepare a proliferation curve of the number of viable bacteria in the bacterial liquid. Meanwhile, bacterial liquid with known viable bacteria number is diluted in stages, culture and multiplication curves are produced in the same mode, and a calibration curve of time to reach fixed turbidity and viable bacteria number is produced. The number of viable bacteria in the bacterial liquid after the reaction was stopped was estimated from the relationship between the time until the fixed turbidity was reached and the calibration curve, and the decrease in the number of bacteria was confirmed.
Regarding the degree of reduction in the bacterial count (log reduction value), the log value of the reduction in bacterial count was used and is shown in Table 1. The larger the value, the higher the in vivo bactericidal activity.
(in vivo sterilizing Property: table 2)
The same operations as described above were performed except that the skin external agent compositions described in table 2 (example 5, comparative example 1 and comparative example 8) were used, and the rest time after the application of the compositions to the skin surface was set to 1, 2, 3, 4, 5 minutes, and data were obtained, respectively. Regarding the degree of reduction in the bacterial count (log reduction value), the log value of the bacterial count reduction was used and is shown in Table 2.
(skin irritation)
The inner side of the forearm of the subject was cleaned using "Biore u Rg" (manufactured by Kagaku corporation), and further cleaned with tap water and pure water. After waiting for 5 to 10 minutes, the skin external preparation composition was discharged from the quantitative discharge container by 5 discharge operations, and a filter paper having a diameter of 9mm (manufactured by patch tester "Torili", LIBATAPE PHARMACEUTICAL Co., ltd.) was applied and impregnated so as to be an amount corresponding to the condition of filling the palm of each hand. The filter paper was placed on the skin surface of the inner portion of the forearm, sealed from above, and left to stand for 60 minutes. After 60 minutes the seal was peeled off and after 30 minutes the skin surface was visually inspected for redness. In table 1, the case of not reddening is denoted as "-", and the case of reddening is denoted as "+".
If evaluated as "-" it means no skin irritation.
TABLE 2
TABLE 2
< formulation ingredients in composition >)
(A) Lactic acid: fuji film and Wako pure chemical industries, ltd. "lactic acid (effective amount: 90%)".
(C1) Citric acid: fuji film and Wako pure chemical industries, ltd.
(C2) Pyrrolidone carboxylic acid: fuji film and Wako pure chemical industries, ltd.
pH regulator: hydrochloric acid aqueous solution with concentration of 1mol/L and/or sodium hydroxide aqueous solution with concentration of 1 mol/L.
Aqueous hydrochloric acid: fuji photo film and Wako pure chemical industries, ltd. "hydrochloric acid (1 mol/L)".
Aqueous sodium hydroxide solution: "48% NaOH (aqueous sodium hydroxide solution)" manufactured by Kanto chemical Co., ltd. Was used after being adjusted so as to be 1mol/L aqueous sodium hydroxide solution.
Benzalkonium chloride: benzylalkanium chloride (50% aqueous solution) manufactured by Tokyo chemical industry Co., ltd "
As can be seen from table 1: if the external skin preparation of this example is used, the bactericidal activity of the skin surface is high and skin irritation can be suppressed. Further, as shown in table 2, it is clear that: unlike the conventional benzalkonium chloride aqueous solution (comparative example 8) as a bactericide, the external skin preparation composition used in this example had the following tendency: that is, after the composition is applied to the skin, the bactericidal activity is not decreased but improved with the lapse of time.
Examples 13 to 29
(discharge test of skin external preparation composition)
The components shown in Table 3 were prepared in amounts, and after mixing at room temperature, the pH was adjusted to the pH value shown in Table 3 using 1mol/L aqueous hydrochloric acid solution and/or 1mol/L aqueous sodium hydroxide solution as a pH adjuster, to prepare a skin external preparation composition. The blending amounts shown in table 3 are effective component amounts (mass%) of the respective components.
The skin external preparation composition was filled into a constant-volume discharge container (stroke spray container X or pump container Y) described in table 3 to obtain a container-containing skin external preparation. The filling amount of the external skin preparation composition was 50mL in the aerosol container X and 120mL in the pump container Y. Further, each discharge operation was performed once, and the amount of the composition discharged by one discharge operation was confirmed. The one-shot ejection operation was performed in a state where a load of 7kg was applied to the stroke of the constant-volume ejection container for 3 seconds.
(in vivo sterilizing Property)
The in vivo bactericidal activity was evaluated in the same manner as in table 1.
(sense of use)
1.0g of the skin external preparation composition shown in Table 3 was discharged, and the mixture was spread over both hands until it was fused, and then dried. Thereafter, the fingertip was wetted with tap water at 20℃and a flow rate of 80mL/s for 1 second, and then the fingertip was wiped dry, and the dry feel at this time was evaluated. The evaluation was performed by 5 professional functional inspectors based on the following criteria, and the average value of the scores was used as the evaluation value.
< case of Using quantitative ejection Container X >)
1: the dry feel was strongly felt as compared with example 13.
2: a dry feel was slightly felt as compared to example 13.
3: equivalent to example 13.
4: the dry feel was slightly weaker than in example 13.
5: the dry feel was weaker than in example 13.
< case of Using quantitative ejection Container Y >)
1: the dry feel was strongly felt as compared with example 16.
2: a dry feel was slightly felt as compared to example 16.
3: equivalent to example 16.
4: less dry feel than example 16
5: the dry feel was weaker than in example 16.
< kind of quantitative ejection Container >
X: a stroke type spray type container (nozzle: Z-155-C110 manufactured by Zhuben container Co., ltd.) was 50mL in volume.
Y: "and and Custom Essence" manufactured by Kagaku corporation is a stroke pump type container having a capacity of 120mL.
< formulation ingredients in composition >)
(A) Lactic acid: "lactic acid (effective amount: 90%)" manufactured by Fuji film and Wako pure chemical industries, ltd.
(B1) Polyvinyl alcohol: "JC-40" manufactured by JAPAN VAM & POVAL Co., ltd., polymerization degree of 4,000, saponification degree of 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 Co., ltd.
pH regulator: hydrochloric acid aqueous solution with concentration of 1mol/L and/or sodium hydroxide aqueous solution with concentration of 1 mol/L.
Aqueous hydrochloric acid: hydrochloric acid (1 mol/L) manufactured by Fuji film and Wako pure chemical industries, ltd "
Aqueous sodium hydroxide solution: "48% NaOH (aqueous sodium hydroxide solution)" manufactured by Kanto chemical Co., ltd. Was used after being adjusted so as to be 1mol/L aqueous sodium hydroxide solution.
[ Industrial applicability ]
The present invention can provide an external preparation for skin which exhibits excellent bactericidal or antiviral properties and has low skin irritation.
Claims (11)
1. A skin external preparation is prepared by storing a skin external preparation composition in a quantitative discharge container,
the composition contains at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or its salt (A),
when the component (A1) is the component (A1) in the acid form of the acid present in the composition, the content of the component (A1) in the composition discharged from the quantitative discharge container by one discharge operation is 0.05mg to 80 mg.
2. The external preparation for skin according to claim 1, wherein,
the amount of the composition discharged from the quantitative discharge container by one discharge operation is 0.05g or more and 3.0g or less.
3. The external preparation for skin according to claim 1 or 2, wherein,
the viscosity of the composition is 1.0-10,000 mPas at 25 ℃.
4. The external preparation for skin according to any one of claim 1 to 3, wherein,
the pH value of the composition at 25 ℃ is 3.5-5.0.
5. The external preparation for skin according to any one of claim 1 to 4, wherein,
the content of the component (A) in the composition is 0.05 mass% or more and 10 mass% or less.
6. The external preparation for skin according to any one of claim 1 to 5, wherein,
the content of the component (A1) in the composition is 0.02 mass% or more and 10 mass% or less.
7. The external preparation for skin according to any one of claim 1 to 6, wherein,
the concentration of metal ions in the composition is 0.002mol/L to 0.50 mol/L.
8. The external preparation for skin according to any one of claim 1 to 7, wherein,
the quantitative discharge container is a stroke-type push-type container, and the one discharge operation is an operation of pushing the container once in a full stroke.
9. The external preparation for skin according to any one of claim 1 to 8, wherein,
the component (A) is lactic acid or a salt thereof,
the mass ratio (C)/(A) of the organic acid or salt (C) thereof other than the component (A) to the component (A) in the composition is less than 1,
the pH value of the composition at 25 ℃ is 3.5-5.0.
10. The external preparation for skin according to any one of claim 1 to 9, wherein,
the composition further comprises a nonionic tackifier (B),
the viscosity of the composition is 100 mPas to 10,000 mPas at 25 ℃.
11. A method for supplying at least 1 acid selected from lactic acid, pyruvic acid and urocanic acid or a salt (A) thereof to an application site on the skin surface, wherein,
comprising the following steps (I) and (II) in order:
step (I): a step of cleaning the application site;
step (II): and a step of discharging the composition from a quantitative discharge container containing the composition containing the component (A) by a single discharge operation and supplying the composition to the application site, wherein, when the component (A1) in the acid form in the acid present in the composition is (A1), the content of the component (A1) in the composition discharged from the quantitative discharge container by a single discharge operation is 0.05mg to 80 mg.
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JP2021-144710 | 2021-09-06 | ||
PCT/JP2022/028041 WO2023032493A1 (en) | 2021-09-06 | 2022-07-19 | External skin preparation |
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CN (1) | CN117897150A (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 |
US6352700B1 (en) * | 1999-05-03 | 2002-03-05 | Fort James Corporation | Lotionized tissue products containing a pH balance compound for the skin |
US10130578B2 (en) * | 2015-07-23 | 2018-11-20 | Johnson & Johnson Consumer Inc. | 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 |
JP2021193078A (en) * | 2020-06-05 | 2021-12-23 | 花王株式会社 | External skin composition for bacteria or virus killing |
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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