WO2023120583A1

WO2023120583A1 - External composition for acne, and external composition for acne bacterium-selective antimicrobial/sterilization

Info

Publication number: WO2023120583A1
Application number: PCT/JP2022/047132
Authority: WO
Inventors: 奈保栗原
Original assignee: ライオン株式会社
Priority date: 2021-12-22
Filing date: 2022-12-21
Publication date: 2023-06-29

Abstract

Provided is an external composition for acne, the composition containing (A) isopropyl methylphenol and one or more components selected from component (B) and component (C) below, and having low effect on growth of Staphylococcus epidermidis as well as excellent antimicrobial/sterilizing effect on Propionibacterium acnes. (B): One or more selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol, and pantothenyl ethyl ether. (C): One or more selected from a polyethylene glycol fatty acid ester, a polyoxyethylene sorbitol fatty acid ester, a sorbitan fatty acid ester, and a polyglycerin fatty acid ester having an HLB of less than 15.0 and a fatty acid chain length of 12-18, and a polyoxyethylene alkyl ether having an alkyl chain length of 12-18.

Description

Composition for external use for acne and composition for external use for selective antibacterial and sterilization of P. acnes

The present invention
(I) Acne topical composition and acnes-selective antibacterial/bactericidal composition containing isopropylmethylphenol; The present invention relates to an antibacterial/bactericidal agent for P. acnes and an antibacterial/bactericidal composition for external use on the skin containing the same.

(I) Isopropyl methylphenol (hereinafter sometimes abbreviated as IPMP) is characterized by a broad antibacterial spectrum compared to cationic disinfecting ingredients such as benzalkonium chloride, so it is used as a disinfectant and acne treatment. used in medicine.

Acne is called acne vulgaris, and the pores are clogged with sebum, and P. acnes is involved in this, causing inflammation. Recent studies have reported that Staphylococcus aureus promotes the formation of biofilms of acne bacteria, and that acne recurs due to the growth of Staphylococcus aureus even if only acne bacteria are removed, suggesting the involvement of Staphylococcus aureus. ing. IPMP is widely used as a bactericidal agent for acne medicines, but because of its broad antibacterial spectrum, it has the problem of sterilizing not only P. acnes but also Staphylococcus epidermidis, which is useful for moisturizing the skin.

(II) In normal healthy human skin, Staphylococcus epidermidis is present as a beneficial indigenous skin bacterium. It is known that an increase in Staphylococcus aureus, which is a resident skin bacterium, exacerbates the symptoms. In addition, the acne bacillus Cutibacterium acnes proliferates in sebum and develops acne vulgaris due to an imbalance of the skin flora. For this reason, external medicines have conventionally contained bactericides such as benzalkonium chloride in order to sterilize and remove these harmful Staphylococcus aureus and Acne bacilli (Patent Document: Japanese Patent Application Laid-Open No. 2000-319171).

On the other hand, when topical drugs containing these bactericides are applied, staphylococcus epidermidis, which is a beneficial bacterium involved in skin barrier function and skin moisturizing effect, is also sterilized. In some cases, a therapeutic effect (skin moisturizing action) could not be obtained.

Japanese Unexamined Patent Application Publication No. 2011-231082 JP-A-2000-319171

(I) The present invention has been made in view of the above circumstances, and is a composition containing isopropylmethylphenol, which has excellent antibacterial and bactericidal effects against P. acnes and has an effect on the growth of Staphylococcus epidermidis. The purpose of the present invention is to provide a composition for external use for acne and a composition for external use for acne bacteria-selective antibacterial and sterilization.
(II) In addition, an antibacterial/bactericidal agent that has excellent antibacterial/bactericidal effects against P. acnes, in particular, has excellent antibacterial/bactericidal effects against P. acnes and does not inhibit the growth of Staphylococcus epidermidis. The purpose of the present invention is to provide an agent (selective antibacterial/bactericidal agent) and an antibacterial/bactericidal composition for external use on the skin containing the same.

(I) As a result of intensive studies to achieve the above object, the present inventors have found that a composition containing (A) isopropylmethylphenol contains (B) pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenate. Thenyl ethyl ether, and (C1) polyethylene glycol fatty acid esters and polyoxyethylene sorbitol fatty acid esters having an HLB of less than 15.0 and a fatty acid chain length of 12 to 18, and polyoxyethylene having an alkyl chain length of 12 to 18 By containing one or more selected from alkyl ethers, the external composition for acne has excellent antibacterial and bactericidal effects against P. acnes, preferably Staphylococcus aureus, and has little influence on the growth of S. epidermidis. The inventors have found that an antibacterial/bactericidal composition for external use selective for P. acnes can be obtained, and have completed the present invention.
(II) In addition, (B) a component selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenyl ethyl ether has an antibacterial and bactericidal action against P. acnes, especially an excellent antibacterial and bactericidal effect against P. acnes. The inventors have found that they have the following properties and that they do not inhibit the growth of Staphylococcus epidermidis, leading to the completion of the present invention.

Accordingly, the present invention provides the following inventions.
[I-1]
An external composition for acne, comprising (A) isopropylmethylphenol and one or more components selected from the following components (B) and (C1).
(B) one or more selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenyl ethyl ether (C1) polyethylene glycol having an HLB of less than 15.0 and a fatty acid chain length of 12 to 18 One or more selected from fatty acid esters, polyoxyethylene sorbitol fatty acid esters, sorbitan fatty acid esters, polyglycerin fatty acid esters, and polyoxyethylene alkyl ethers having an alkyl chain length of 12 to 18
[I-2]
The topical composition for acne according to I-1, wherein the content of component (A) is 0.01 to 0.3% by mass.
[I-3]
The composition for external use for acne according to I-1 or I-2, wherein the total content mass ratio of the component (B) and the component (C1) to the content of the component (A) is 1-350.
[I-4]
The external composition for acne according to any one of I-1 to I-3, comprising the component (A), the component (B), and the component (C1).
[I-5]
(A) isopropylmethylphenol and one or more components selected from the following components (B) and (C1): acnes-selective antibacterial/sterilizing composition for external use.
(B) one or more selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenyl ethyl ether (C1) polyethylene glycol having an HLB of less than 15.0 and a fatty acid chain length of 12 to 18 One or more selected from fatty acid esters, polyoxyethylene sorbitol fatty acid esters, sorbitan fatty acid esters, polyglycerin fatty acid esters, and polyoxyethylene alkyl ethers having an alkyl chain length of 12 to 18
[I-6]
The topical composition for selective antibacterial/bactericidal use according to I-5, which is antibacterial/bacterial against P. acnes and Staphylococcus aureus but not antibacterial/bacterial against Staphylococcus epidermidis.
[I-7]
The topical composition for acne bacteria-selective antibacterial/bactericidal composition according to I-5 or I-6, containing the component (A), the component (B), and the component (C1).
[II-1]
(B) An antibacterial/bactericidal agent against P. acnes, containing as an active ingredient one or more selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenyl ethyl ether.
[II-2]
Furthermore, (C2) polyethylene glycol fatty acid esters, polyoxyethylene sorbit fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters and polyglycerin fatty acid esters having a fatty acid chain length of 12 to 18, and alkyl chain lengths of 12 to 18. The antibacterial/bactericidal agent according to II-1, containing one or more selected from polyoxyethylene alkyl ethers.
[II-3]
The antibacterial/disinfectant according to II-1 or II-2, which is a selective antibacterial/disinfectant.
[II-4]
The selective antibacterial/bactericidal agent according to II-2, which is antibacterial/bacterial against P. acnes and Staphylococcus aureus but not antibacterial/bacterial against Staphylococcus epidermidis.
[II-5]
The antibacterial/bactericidal agent according to any one of II-2 to II-4, wherein the component (C2) has an HLB of 10 to 18.
[II-6]
The antibacterial/bactericidal agent according to any one of II-2 to II-5, wherein the content mass ratio represented by (C2)/(B) is 0.03 to 40.
[II-7]
(D) hydrogen peroxide, sodium hypochlorite, ethanol, isopropanol, ovanol, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, cresol, popillon iodine, iodine, sodium dichloroisocyanurate, chlorhexidine and acrinol, and ( A) The antibacterial/bactericidal agent according to any one of II-1 to II-6, wherein the content of isopropylmethylphenol is 0.3% by mass or less.
[II-8]
An antibacterial/bactericidal skin composition for external use against P. acnes, containing the antibacterial/bactericidal agent according to any one of II-1 to II-7.

(I) According to the present invention, an external composition for acne, a selective antibacterial/bactericidal external application for acne bacteria, which has excellent antibacterial and bactericidal effects against acne bacteria and has a low influence on the growth of Staphylococcus epidermidis A composition can be provided.
(II) In addition, according to the present invention, an antibacterial/bactericidal agent having excellent antibacterial/bactericidal effects against P. acnes, particularly having excellent antibacterial/bactericidal effects against P. acnes and inhibiting the growth of Staphylococcus epidermidis It is possible to provide an antibacterial/bactericidal agent (selective antibacterial/bactericidal agent) against P. acnes, and an antibacterial/bactericidal external composition for skin containing the same.

FIG. 2 is a binary minimum inhibitory concentration diagram of panthenol, polyethylene glycol monolaurate (10EO), and a mixture of panthenol and polyethylene glycol monolaurate (10EO) against Acne bacilli. FIG. 2 is a binary minimum inhibitory concentration diagram of panthenol, polyethylene glycol monolaurate (10EO), and a mixture of panthenol and polyethylene glycol monolaurate (10EO) against Staphylococcus aureus. FIG. 2 is a binary minimum inhibitory concentration diagram of panthenol, polyethylene glycol monolaurate (10EO), and a mixture of panthenol and polyethylene glycol monolaurate (10EO) against S. epidermidis.

The present invention will be described in detail below.
Embodiment (I) of the present invention is a topical composition for acne containing (A) isopropylmethylphenol and one or more components selected from the following components (B) and (C1). .
(B) one or more selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenyl ethyl ether (C1) polyethylene glycol having an HLB of less than 15.0 and a fatty acid chain length of 12 to 18 One or more selected from fatty acid esters, polyoxyethylene sorbite fatty acid esters, sorbitan fatty acid esters, polyglycerin fatty acid esters, and polyoxyethylene alkyl ethers having an alkyl chain length of 12 to 18 Hereinafter, "composition for external use for acne", " P. acnes-selective antibacterial/sterilizing composition for external use” is collectively referred to as “composition”.

[(A) Component]
The (A) component of the present invention is (A) isopropylmethylphenol. IPMP is a bactericidal agent that is effective against diseases such as eczema, dermatitis, and acne that are likely to be aggravated by bacteria and fungi. Therefore, it is effective for acne treatment and prevention.

The content of component (A) is preferably 0.01 to 0.3% by mass, more preferably 0.03 to 0.3% by mass, relative to the composition in the embodiment (I) of the present invention, 0.05 to 0.3% by mass is more preferable. When the amount is 0.01% by mass or more, the bactericidal/antibacterial effect against P. acnes is easily obtained, and when the amount is 0.3% by mass or less, the growth of Staphylococcus epidermidis is less likely to be inhibited. Isopropylmethylphenol has lower bactericidal activity per unit concentration than quaternary ammonium salt-type bactericides such as benzalkonium chloride, is oil-soluble, and has extremely low solubility in water. If the content of isopropylmethylphenol is increased in anticipation of enhanced sterilizing power, precipitation at low temperatures and destabilization of the emulsion tend to occur. The above problem can be improved by containing ethanol or a surfactant solubilizer with HLB of 15.0 or more, but if sterilization commensurate with the content of isopropylmethylphenol cannot be obtained, or if it is applied to the skin There was a case where the feeling of use when it was used decreased. In the present invention, by blending one or more selected from the component (B) and the component (C1), even if the amount of the component (A) is reduced, the desired bactericidal and antibacterial effects against acne bacteria can be obtained. Therefore, the above problem can also be solved.

[(B) component]
The component (B) of the present invention is one or more selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenyl ethyl ether, and can be used singly or in combination of two or more. . Component (B) has excellent antibacterial and bactericidal effects against P. acnes, and has little effect on the growth of Staphylococcus epidermidis. In addition, when the component (A) alone does not exhibit a bactericidal/antibacterial effect against P. acnes, the content of the component (A) (less than 0.1% by mass) does not show a bactericidal/antibacterial effect. Antibacterial and bactericidal effects can be obtained selectively. In addition, when the (A) component alone exhibits a bactericidal and antibacterial effect against Staphylococcus epidermidis, the content of the (A) component (0.1% by mass or more), which is combined with the (B) component, causes Staphylococcus epidermidis It is possible to reduce the impact on growth against

From the viewpoint of effectiveness, panthenol and pantothenyl ethyl ether are preferable as the component (B). Panthenol, which is a water-soluble vitamin, is known to have anti-inflammatory action, activation of skin cells, enhancement of skin elasticity and water retention, and the like.

Panthenol and salts of pantothenic acid such as calcium pantothenate and sodium pantothenate are converted to pantothenic acid inside the skin and exhibit the above pharmacological effects. Pantothenyl ethyl ether is the ethyl ether of panthenol, which like panthenol is converted to pantothenic acid in the body.

The content of component (B) is preferably 0.1 to 2% by mass with respect to the composition in the embodiment (I) of the present invention, and 0.1 to 1 % by mass is more preferred, and 0.3 to 1% by mass is even more preferred. By making it 0.1% by mass or more, the bactericidal and antibacterial effects against acne bacteria are improved. Moreover, the influence on growth of Staphylococcus epidermidis becomes low by making it 0.1 mass % or more and 2 mass % or less.

[(C1) Component]
Component (C1), which is the embodiment (I) of the present invention, has an HLB of less than 15.0 and a fatty acid chain length of 12 to 18. Polyethylene glycol fatty acid ester, polyoxyethylene sorbitol fatty acid ester, sorbitan fatty acid It is one or more selected from esters, polyglycerin fatty acid esters, and polyoxyethylene alkyl ethers having an alkyl chain length of 12 to 18, and can be used singly or in combination of two or more.

The fatty acid chain length or alkyl chain length of component (C1) is 12 to 18, with 12, 14 and 18 being preferred. By setting it as such fatty acid chain length or alkyl chain length, an antibacterial / bactericidal effect improves. In particular, when the carbon chain length or alkyl chain length is 12, 14 and 18, the component (A) alone does not exhibit a bactericidal / antibacterial effect, and the component (C1) is added to prevent acne. Antibacterial and bactericidal effects can be obtained selectively against bacteria. In addition, (A) component alone exhibits a bactericidal and antibacterial effect against Staphylococcus epidermidis, and in the content of (A) component, by also containing (C1) component, the effect on the growth of Staphylococcus epidermidis can be lowered. The number of added moles of polyoxyethylene is preferably 6 to 60, more preferably 6 to 55, even more preferably 6 to 40, particularly preferably 6 to 25, and most preferably 10. By making it more than the said minimum, the antibacterial / bactericidal effect with respect to P. acnes and Staphylococcus aureus improves more. When the amount is equal to or less than the above upper limit, the influence on the growth of Staphylococcus epidermidis is reduced. Furthermore, it is preferable that it is liquid at normal temperature because it has excellent antibacterial and bactericidal effects against P. acnes and Staphylococcus aureus and has less influence on the growth of Staphylococcus epidermidis.

The HLB of component (C1) is less than 15.0, preferably 10.0 to 13.0. Within the above range, it becomes easier to interact with the cell walls and cell membranes of bacteria, so that excellent antibacterial and bactericidal effects against P. acnes and Staphylococcus aureus are likely to be obtained. HLB (Hydrophile-Lipophile Balance) is an index of affinity for water and oil, and in general, the closer to 0, the higher the lipophilicity, and the closer to 20, the higher the hydrophilicity. HLB can be calculated by any one of the Atlas method, Griffin method, Davis method, Kawakami method, etc., and the value published by the manufacturer of the product can be taken into consideration. HLB in the present specification is "Handbook-Cosmetics/Drug Ingredients-Revised Edition", published by Nikko Chemicals Co., Ltd., February 1, 1977, revised edition, pp. 854-855. It is calculated based on As a specific method for determining the HLB value, the component (C1) is combined with sorbitan monostearate (NIKKOL SS-10, HLB 4.7) as a standard emulsifier, and the total amount of these two emulsifiers is Emulsify the liquid paraffin (HLB 10.1), which is the material to be emulsified, by keeping the ratio constant and changing only the ratio, and after leaving it for a day and night, the optimum emulsifier where stability is obtained from the amount of creaming, cloudiness, water separation of the lower layer, etc. and the HLB value x of the component (C1) is calculated by the following formula (1).
y = (x x amount used (% by mass) + z x amount used (% by mass))/100 Formula (1)
Here, in the formula (1), "x" indicates the HLB value of the component (C1), "y" indicates the HLB value of liquid paraffin, and "z" indicates sorbitan monostearate (NIKKOL SS-10) shows the HLB value. The HLB value of the liquid paraffin was determined by the same method using a combination of sorbitan monostearate (NIKKOL SS-10, HLB 4.7) and POE sorbitan monostearate (NIKKOL TS-10, HLB 14.9). can ask.

Examples of polyethylene glycol fatty acid esters having a fatty acid chain length of 12 to 18 include polyethylene glycol monooleate (10EO), polyethylene glycol monooleate (6EO), polyethylene glycol monolaurate (10EO), and polyethylene glycol monostearate (10EO). are mentioned. Numerical values in parentheses in the description of the polyethylene glycol fatty acid esters exemplified above represent the average degree of polymerization of ethylene oxide, that is, the average number of repeating oxyethylene groups. The same applies to the following polyoxyethylene sorbite fatty acid esters and polyoxyethylene alkyl ethers.

Examples of polyoxyethylene sorbitol fatty acid esters having a fatty acid chain length of 12 to 18 include polyoxyethylene sorbitol tetrastearate (60EO), polyoxyethylene sorbitol tetraoleate (60EO), polyoxyethylene sorbitol tetraoleate (40EO), polyoxyethylene sorbitol tetraoleate (30EO) and the like.

As the sorbitan fatty acid ester with a fatty acid chain length of 12-18, the fatty acid chain length is preferably 12-18, more preferably 12. Monoesters are also preferred. Specific examples include sorbitan monolaurate, sorbitan monostearate, sorbitan monooleate, sorbitan sesquioleate and the like.

Polyglycerin fatty acid esters with a fatty acid chain length of 12 to 18 include polyglycerin fatty acid esters such as decaglyceryl monomyristate, polyglyceryl-10 monostearate, and polyglyceryl-10 monooleate. The numerical value at the end of the notation of the polyglycerin fatty acid ester exemplified above represents the average degree of polymerization of glycerin.

Examples of polyoxyethylene alkyl ethers having an alkyl chain length of 12 to 18 include polyoxyethylene (4) lauryl ether, polyoxyethylene (9) lauromacrogol such as lauryl ether; polyoxyethylene (10) cetyl ether, polyoxyethylene Ethylene (10) oleyl ether and the like can be mentioned.

The (C1) component is preferably a polyethylene glycol (4-20 EO) fatty acid ester having a fatty acid chain length of 12-18, preferably a monoester, from the standpoint of sustained moistness (moisturizing feeling).

The content of the component (C1) is preferably 0.1% by mass or more in the composition in the embodiment (I) of the present invention from the viewpoint of having more antibacterial and bactericidal effects, and the effect on the growth of Staphylococcus epidermidis is preferably 10% by mass or less, more preferably 0.1 to 8% by mass, even more preferably 0.3 to 6% by mass, and particularly preferably 1 to 3% by mass. By making it more than the said lower limit, the antibacterial / bactericidal effect with respect to P. acnes and Staphylococcus aureus improves more. By making it below the said upper limit, the influence on the growth of Staphylococcus epidermidis becomes lower.

In the embodiment (I) of the present invention, the influence of the growth of Staphylococcus epidermidis is reduced by containing the component (A) and one or more selected from the components (B) and (C1). Antibacterial and bactericidal effects against acne bacteria can be obtained. It is preferable to contain the component (A), the component (B), and the component (C1) in order to obtain this effect with a small content of the component (A). By containing components (A) to (C1), excellent antibacterial and bactericidal effects against Staphylococcus aureus can be obtained in addition to P. acnes.

In the embodiment (I) of the present invention, the total content mass ratio of the component (B) and the component (C1) to the content of the component (A) ((B) + (C1)) / (A)) is preferably 1 to 350, more preferably 3 to 200, and more preferably 8 to 150. By making it more than the said lower limit, the antibacterial / bactericidal effect with respect to P. acnes and Staphylococcus aureus is improved more, and it can exhibit the antibacterial / bactericidal effect aimed at with little content of (A) component. By making it below the said upper limit, the influence on the growth of Staphylococcus epidermidis becomes lower.

In the embodiment (I) of the present invention, the upper limit of the content mass ratio of component (B) to the content of component (A) (referred to as the (B)/(A) mass ratio) is preferably 150 or less. , 100 or less, and even more preferably 50 or less. The lower limit of the (B)/(A) mass ratio may be 0, more preferably 1 or more, and even more preferably 3 or more. Further, the lower and upper limits of the (B)/(A) mass ratio are more preferably 1-100, and even more preferably 3-50. By making it more than the said lower limit, the antibacterial / bactericidal effect with respect to P. acnes and Staphylococcus aureus is improved more, and it can exhibit the antibacterial / bactericidal effect aimed at with little content of (A) component. By making it below the said upper limit, the influence on the growth of Staphylococcus epidermidis becomes lower.

In the embodiment (I) of the present invention, the upper limit of the content mass ratio of the component (C1) to the content of the component (A) (referred to as the (C1)/(A) mass ratio) is preferably 250 or less. , is more preferably 200 or less, and even more preferably 100 or less. The lower limit of the (C1)/(A) mass ratio may be 0, more preferably 2 or more, and even more preferably 5 or more. Further, the lower and upper limits of the (C1)/(A) mass ratio are more preferably 2 to 200, and even more preferably 5 to 100. By making it more than the said lower limit, the antibacterial / bactericidal effect with respect to P. acnes and Staphylococcus aureus is improved more, and it can exhibit the antibacterial / bactericidal effect aimed at with little content of (A) component. When the content is equal to or less than the above upper limit, the composition of the present invention does not deteriorate the feeling of use (stickiness, etc.) when applied to the skin, and the effect on the growth of Staphylococcus epidermidis is reduced.

[Composition for external use for acne, composition for external use for acne bacteria-selective antibacterial and sterilization]
The composition in embodiment (I) of the present invention is applied in an appropriate amount (depending on the application area, but generally 0.1 to 0.5 g [solid or semi-solid such as cream, gel, etc.)]. Form formulation], 1 to 5 mL [liquid formulation such as lotion, aerosol]) is applied to the skin, at least acne bacteria are antibacterial and sterilized, and the effect on the growth of Staphylococcus epidermidis, which is a resident skin bacterium. is low. Preferably, since an antibacterial and bactericidal effect against Staphylococcus aureus, a harmful Gram-positive bacterium, is obtained, these bacteria are selectively antibacterial and sterilized, and the effect on the growth of Staphylococcus epidermidis, which is a resident skin bacterium. low. For these uses, the composition for external use may contain the component (A) and one or more selected from the components (B) and (C1). ) component, (B) component, and (C1) component. The composition of the present invention is suitable as an external composition for acne, prevention of acne, treatment of acne, amelioration of acne, and skin moisturizing. In addition, it is suitable as an external composition for acne bacteria selective antibacterial / sterilization that has antibacterial / sterilizing against P. acnes and less influence on the growth of Staphylococcus epidermidis, and is antibacterial against P. acnes and Staphylococcus aureus. · It is also suitable as an external composition for acne bacteria selective antibacterial / sterilization (multiple selective antibacterial / sterilization external composition) that sterilizes and has little influence on the growth of Staphylococcus epidermidis.
The judgment criteria for "antibacterial/sterilization" and "low effect on growth" are based on the examples described later.

In addition, in the composition in the embodiment (I) of the present invention, in particular, in the composition for external use for acne bacteria-selective antibacterial and sterilization, from the viewpoint that the effect on the growth of Staphylococcus epidermidis is low, sterilization in the external preparation The ingredients hydrogen peroxide, sodium hypochlorite, isopropanol, ovanol, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, cresol, popillon iodine, iodine, sodium dichloroisocyanurate, chlorhexidine and acrinol are substantially (effective concentration). Not containing substantially means less than 0.3% by mass, more preferably less than 0.1% by mass, more preferably less than 0.01% by mass, and does not contain (below the detection limit) of the composition. Especially preferred.

The dosage form and properties of the composition in the embodiment (I) of the present invention are not particularly limited as long as they can be applied transdermally, and are liquid, solid, semi-solid (gel, ointment, paste, foam). and so on. Moreover, the embodiment may be in any form such as an external skin drug, an external skin quasi-drug, a cosmetic, a skin cleanser (such as a facial cleanser), and the like. The formulation form of the composition is not particularly limited, and examples include ointments, creams, lotions, gels, emulsions, liquids, patches, mists, foamy sprays, mists, and powders. , foamy or paste-like aerosol agents, pack agents, body shampoos, hair shampoos, rinses, and the like. Among them, ointments, creams, lotions, gels, aerosols, sprays, emulsions, and packs are preferable, and creams, lotions, emulsions, foamy aerosols, and foamy jets. Pump sprays are more preferred. The emulsified state of creams, milky lotions, etc. is not particularly limited, and may be any of W/O, O/W, W/O/W, and O/W/O.

By applying the composition according to the embodiment (I) of the present invention, a moisturizing effect can be obtained from the selective antibacterial and bactericidal effects, and a moisturizing effect can also be obtained. The reason for this is that it has little effect on the growth of Staphylococcus epidermidis, which is a resident skin bacterium. Staphylococcus epidermidis breaks down sweat and sebum to produce fatty acids and glycerin. Fatty acids keep the skin slightly acidic and produce antibacterial peptides, which can prevent the growth of Staphylococcus aureus. In addition, the produced glycerin is a moisturizing ingredient that gives moisture to the skin and plays a role in maintaining the skin barrier function, so that a moisturizing effect can be obtained and a moisturizing feeling can be obtained. In post-pubertal acne (so-called adult acne), the moisturizing function of the stratum corneum is reduced, making it easier to dry. When the skin is dry, the keratin becomes hard and clogged pores are likely to occur, creating an environment in which anaerobic P. acnes can easily proliferate (inflammation is induced and acne occurs). Therefore, it is important to prevent the skin from drying out. From the above, the antibacterial/bactericidal agent of the present invention is suitable as an acne-reducing agent, a skin moisturizing agent, or an agent having both effects.

The pH of the composition in the embodiment (I) of the present invention is preferably 3 or higher, preferably 3.0 or higher, and more preferably 3.5 or higher, from the viewpoint of antibacterial/bactericidal performance against P. acnes. The upper limit of pH is preferably 10 or less, more preferably 9 or less from the viewpoint of skin irritation. The measurement of pH is based on the Japanese Pharmacopoeia 18th Edition, General Test Methods (measurement temperature: 25°C).

The composition according to the embodiment (I) of the present invention may contain various active ingredients used in pharmaceuticals, quasi-drugs, cosmetics, etc., as necessary, as long as the effects of the invention are not impaired. good. For example, anti-inflammatory agents, antihistamines, antipruritics, wound healing agents, local anesthetics, blood vessel repair agents, keratin softeners, vitamins (excluding component (B)), surfactants (excluding component (C1)), A cooling agent, a moisturizing agent, amino acids, etc. can be contained, and the following ingredients are exemplified.

Anti-inflammatory agents include, for example, tranexamic acid, glycyrrhetinic acid, glycyrrhizic acid or pharmaceutically acceptable derivatives and salts thereof (e.g., dipotassium glycyrrhizinate), licorice extracts, steroid compounds (hydrocortisone, prednisolone, methylprednisolone , clobetasone, betamethasone, dexamethasone, cortisone, flumethasone, beclomethasone, fluticasone or their pharmaceutically acceptable derivatives and their salts), indomethacin, ibuprofen, ibuprofenpiconol, bufexamac, ufenamate, piroxicam, ketoprofen, salicylic acid or its pharmaceuticals and their salts, dimethylisopropylazulene, angelica extract, radish extract and the like.

Examples of antihistamines include diphenhydramine, chlorpheniramine, mequitazine, azelastine, emedastine, ketotifen, or pharmaceutically acceptable derivatives and salts thereof. Diphenhydramine hydrochloride and chlorpheniramine maleate are preferred.

Examples of antipruritic agents include crotamiton, nonylic acid vanillylamide, capsaicin, benzyl nicotinate, capsicum tincture, and the like. Examples of wound healing agents include allantoin, zinc oxide, and the like.
Examples of local anesthetics include lidocaine, lidocaine hydrochloride, dibucaine, dibucaine hydrochloride, and the like.
Examples of vasoconstrictors include naphazoline, tetrahydrozoline, methylephedrine or salts thereof, and the like.
Examples of keratin softeners include urea, sulfur, salicylic acid or pharmaceutically acceptable derivatives thereof and salts thereof, nicotinamide, kaolin, bentonite, and the like.

Vitamins other than component (B) include vitamin A [retinol and its pharmaceutically acceptable derivatives and salts thereof (e.g., retinol palmitate, retinol acetate, retinol, retinal, retinoic acid, retinoid, etc.). )], vitamin _B6 [pyridoxine and its pharmaceutically acceptable derivatives and their salts (e.g., pyridoxine, pyridoxal, etc.)], vitamin C [ascorbic acid and its pharmaceutically acceptable derivatives and their salts (For example, ascorbic acid, sodium ascorbate, magnesium ascorbate phosphate, 3-sodium ascorbyl palmitate phosphate, erythorbic acid, 2-glucoside ascorbate, ascorbyl palmitate, etc.)], vitamin E [tocopherol and its pharmaceutically Acceptable derivatives and salts thereof (e.g. d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, mixed tocopherol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, vitamin E acetate (tocopherol acetate), vitamin E nicotinate, vitamin E succinate, vitamin E linolenate, natural vitamin E, etc.)], vitamin B ₁ [thiamine and its pharmaceutically acceptable possible derivatives and salts thereof (e.g., thiamine hydrochloride, thiamine nitrate, etc.)], vitamin _B2 [riboflavin and its pharmaceutically acceptable derivatives and salts thereof (e.g., riboflavin phosphate, riboflavin sodium phosphate, butyric acid riboflavin, flavin adenine dinucleotide sodium, etc.)], vitamin _B3 [nicotinic acid and its pharmaceutically acceptable derivatives and salts thereof (nicotinamide, benzyl nicotinate, etc.)], vitamin _B12 [cobalamin and derivatives thereof, pharmaceutically acceptable derivatives thereof and salts thereof (e.g., cyanocobalamin, mecobalamin, hydroxocobalamin hydrochloride, etc.)], biotin, folic acid and pharmaceutically acceptable derivatives thereof and salts thereof, vitamin Ds [Calciferol and its pharmaceutically acceptable derivatives and salts thereof (e.g., ergocalciferol, cholecalciferol, etc.)], other vitamins (e.g., hesperidin, carnitine, ferulic acid, γ-oryzanol, orotic acid, rutin, eriocitrin, inositol, and pharmaceutically acceptable derivatives and salts thereof) and the like.

Examples of surfactants other than the component (C1) include nonionic surfactants other than the component (C1), ionic surfactants, and the like. Nonionic surfactants include, for example, polyoxyethylene glycerol fatty acid esters such as polyoxyethylene glyceryl monostearate (15); polyoxyethylene tristearate (20) sorbitan (polysorbate 65); Polyoxyethylene sorbitan fatty acid esters such as ethylene (20) sorbitan (polysorbate 85); polyoxyethylene castor oils such as polyoxyethylene (60) castor oil; polyoxyethylene hydrogenated castor oil (10), polyoxyethylene hydrogenated castor oil (60) and other polyoxyethylene hydrogenated castor oils. In addition, polyethylene glycol fatty acid esters with HLB of 15.0 or more, polyoxyethylene sorbitol fatty acid esters, sorbitan fatty acid esters (polyoxyethylene monooleate (20) sorbitan (polysorbate 80), etc.), polyglycerin fatty acid esters and polyoxyethylene Alkyl ethers may also be mentioned. Examples of the ionic surfactant include N-coconut oil fatty acid acyl-DL-alanine triethanolamine liquid. Examples of the ionic surfactant include N-coconut oil fatty acid acyl-DL-alanine triethanolamine liquid.

When a surfactant other than component (C1) is contained, it is preferable that the content in the composition for external use is low in order to reduce the influence on the growth of Staphylococcus epidermidis. Specifically, it is preferably less than 3% by mass in the composition, more preferably less than 0.5% by mass, even more preferably 0.01% by mass or less, and particularly preferably not contained (below the detection limit).

Cooling agents include, for example, l-menthol, camphor, borneol or analogues thereof, fennel oil, eucalyptus oil, peppermint oil, peppermint oil, spearmint oil and the like.

Moisturizers include, for example, polyhydric alcohols (glycerin, 1,3-butylene glycol, 1,2-pentadiol, etc.), sugar alcohols (sorbit, etc.), hyaluronic acid or derivatives thereof, heparin-like substances, polymer compounds ( collagen, chitosan, etc.), amino acids, natural moisturizing factors (sodium lactate, urea, etc.), ceramides, vegetable oils (olive oil, etc.), plant extracts (soybean extract, chamomile extract, aloe extract, etc.).

Examples of amino acids include glutamic acid, aspartic acid, glycine, alanine, serine, aminoethylsulfonic acid (taurine), and pharmaceutically acceptable salts thereof (e.g., ephedrine hydrochloride, methylephenoline hydrochloride, etc.). be done.

Other hydrocarbons such as vaseline, paraffin, liquid paraffin, squalane, ceresin, gelling hydrocarbons and microcrystalline wax; higher fatty acids such as stearic acid, isostearic acid, myristic acid, palmitic acid, oleic acid and behenic acid; cetanol , higher fatty alcohols such as stearyl alcohol and behenyl alcohol; fatty acid ester oils such as isopropyl myristate, octyldodecyl myristate, isopropyl palmitate and diisopropyl adipate; Fatty acid esters; polyhydric alcohols such as propylene glycol and polyethylene glycol; organic solvents such as acetone, methyl ethyl ketone and ethyl acetate; diisopropanolamine, triethanolamine, lauric acid diethanolamide, sodium hydroxide, hydrochloric acid, citric acid, sodium citrate , pH adjusters such as potassium dihydrogen phosphate and sodium hydrogen phosphate; chelating agents such as disodium edetate, ethylenediaminetetraacetate, edetate, pyrophosphate, hexametaphosphate, citric acid, tartaric acid, gluconic acid, etc. ; preservatives such as parabens (methylparaben, ethylparaben, butylparaben), boric acid and borax; cellulose derivatives such as hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, carmellose, croscarmellose, ethylcellulose and methylcellulose; Modified starch, polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, crospovidone, polyethylene glycol, xanthan gum, carrageenan, sodium alginate, gum arabic, guar gum, tamarint gum, karaya gum, carob gum, tragacanth gum, locust bean gum, pullulan, gelatin , carboxyvinyl polymer, acrylic acid/methacrylate alkyl copolymer, sodium polyacrylate, hydroxyethyl acrylate/acryloyldimethyltaurate crosslinked polymer, quince seed (quince), casein, dextrin, sodium pectate, dimethylacrylamide/ Acryloyldimethyltaurate cross-linked polymer, dialkyldimethylammonium sulfate cellulose, bentonite, hectorite, magnesium aluminosilicate, laponite, thickeners such as silicic anhydride, mixed fragrances such as citrus, floral, rose, etc. Essential oils (natural fragrances) such as peppermint oil, eucalyptus oil, bergamot oil, rose oil, rosemary oil, lavender oil and lemon oil, and pearl agents such as ethylene glycol distearate.

The composition in the embodiment (I) of the present invention is prepared by mixing the component (A), one or more selected from the components (B) and (C1), and optional components as necessary. Obtainable. Also, from the viewpoint of formulation stability, ethanol may be blended, and in that case, the content is preferably 0.05 to 5% by mass relative to the composition.

Embodiment (II) of the present invention is an antibacterial against acne bacteria containing as an active ingredient one or more selected from (B) pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenyl ethyl ether • It is a fungicide.
Embodiment (II) of the present invention will be described in detail below.

[(B) component]
The (B) component in the embodiment (II) of the present invention is one or more selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenyl ethyl ether, and More than one species can be used in combination. Component (B) has an excellent antibacterial/bactericidal effect against P. acnes and does not inhibit the growth of Staphylococcus epidermidis. This is new knowledge of the inventor.

The content of component (B) is preferably 0.5% by mass or more in the antibacterial/bactericidal agent because it has more antibacterial/bactericidal effects, and 2% by mass or less because it does not further inhibit the growth of Staphylococcus epidermidis. Preferably, 1 to 2% by mass is more preferable. When the component (C2), which will be described later, is used in combination, the content is preferably 0.1 to 2% by mass, more preferably 0.5 to 2% by mass, because antibacterial and bactericidal effects can be obtained at a lower content.

[(C2) component]
Component (C2) in the embodiment (II) of the present invention includes polyethylene glycol fatty acid esters having a fatty acid chain length of 12 to 18, polyoxyethylene sorbit fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters and polyglycerin. It is one or more selected from fatty acid esters and polyoxyethylene alkyl ethers having an alkyl chain length of 12 to 18, and can be used singly or in combination of two or more.

In the embodiment (II) of the present invention, by combining the component (B) and the component (C2), the antibacterial/bactericidal effect against P. acnes is further improved, and the antibacterial/bactericidal effect against Staphylococcus aureus is excellent. It can be used as a multiple selective antibacterial/bactericidal agent that is effective and does not inhibit the growth of Staphylococcus epidermidis.

The (C2) component has a fatty acid chain length or alkyl chain length of 12 to 18, preferably 12 and 18. By setting it as such fatty acid chain length or alkyl chain length, an antibacterial / bactericidal effect improves. The number of added moles of polyoxyethylene is preferably 6 to 55, more preferably 6 to 40, still more preferably 6 to 25, and particularly preferably 10. By making it more than the said minimum, the antibacterial / bactericidal effect with respect to P. acnes and Staphylococcus aureus improves more. By making it below the above upper limit, the growth of Staphylococcus epidermidis is not further inhibited. Furthermore, it is preferable to be liquid at room temperature because it has excellent antibacterial and bactericidal effects against P. acnes and Staphylococcus aureus and does not inhibit the growth of Staphylococcus epidermidis. Moreover, the upper limit of HLB of the component (C2) is preferably 18.0 or less, more preferably less than 15.0. The lower limit of HLB of component (C2) is preferably 10.0 or more, more preferably 11.0 or more. In addition, the lower and upper limits of the HLB of component (C2) are preferably 10-18, more preferably 11-15. Within the above range, it becomes easier to interact with the cell walls and cell membranes of bacteria, so that excellent antibacterial and bactericidal effects against P. acnes and Staphylococcus aureus are likely to be obtained. HLB (Hydrophile-Lipophile Balance) is as described in the embodiment (I).

Examples of polyethylene glycol fatty acid esters having a fatty acid chain length of 12 to 18 include polyethylene glycol monooleate (10EO), polyethylene glycol monooleate (6EO), polyethylene glycol monolaurate (10EO), and polyethylene glycol monostearate (10EO). are mentioned. Numerical values in parentheses in the description of the polyethylene glycol fatty acid esters exemplified above represent the average degree of polymerization of ethylene oxide, that is, the average number of repeating oxyethylene groups. The same applies to the following polyoxyethylene sorbitol fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and polyoxyethylene alkyl ethers.

Examples of polyoxyethylene sorbitol fatty acid esters having a fatty acid chain length of 12 to 18 include polyoxyethylene sorbitol monolaurate (6EO), polyoxyethylene sorbitol tetrastearate (60EO), polyoxyethylene sorbitol tetraoleate (60EO), tetra Polyoxyethylene sorbitol oleate (40EO), polyoxyethylene sorbitol tetraoleate (30EO), and the like.

Examples of polyoxyethylene sorbitan fatty acid esters having a fatty acid chain length of 12 to 18 include polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan tristearate (polysorbate 65), and monooleic acid. Polyoxyethylene (20) sorbitan (polysorbate 80) and the like.

Examples of polyglycerol fatty acid esters having a fatty acid chain length of 12 to 18 include polyglyceryl-6 monolaurate, decaglyceryl monomyristate, polyglyceryl-10 monostearate, and polyglyceryl-10 monooleate. . The numerical value at the end of the notation of the polyglycerin fatty acid ester exemplified above represents the average degree of polymerization of glycerin.

The (C2) component is preferably a polyethylene glycol (4-20 EO) fatty acid ester having a fatty acid chain length of 12-18, preferably a monoester, from the standpoint of sustained moistness (moisturizing feeling).

The content of component (C2) is preferably 0.1% by mass or more in the antibacterial/bactericidal agent because it has more antibacterial/bactericidal effects, and is preferably 10% by mass or less because it does not further inhibit the growth of Staphylococcus epidermidis. , more preferably 0.2 to 8% by mass, more preferably 0.7 to 6% by mass. By making it more than the above lower limit, the antibacterial/bactericidal effect against P. acnes and Staphylococcus aureus is further improved, and the intended antibacterial/bacterial effect can be exhibited with a smaller content. By making it below the above upper limit, the growth of Staphylococcus epidermidis is not further inhibited.

When containing component (C2), the content mass ratio represented by (C2) / (B) is preferably 0.03 to 40, more preferably 1 to 40, further preferably 1 to 15, and 1.3 to 5 is particularly preferred. By making it more than the said lower limit, the antibacterial / bactericidal effect with respect to P. acnes and Staphylococcus aureus improves more. In particular, even when the content of component (B) is small, the antibacterial and bactericidal effects against Staphylococcus aureus are further improved. By making it below the said upper limit, growth of Staphylococcus epidermidis is not inhibited more.

[(D) component]
From the viewpoint of not inhibiting the growth of Staphylococcus epidermidis, (D) hydrogen peroxide, sodium hypochlorite, ethanol, isopropanol, ovanol, chloride The content of benzalkonium, benzethonium chloride, cetylpyridinium chloride, cresol, popillon-iodine, iodine, sodium dichloroisocyanurate, chlorhexidine and acrinol, and component (A): isopropylmethylphenol shall be 0.3% by mass or less. is desirable.

In the present invention, the component (D) has an excellent antibacterial/bactericidal effect against acne bacteria and does not inhibit the growth of Staphylococcus epidermidis, so the content in the antibacterial/bactericidal agent is less than 0.3% by mass. is more preferable, less than 0.1% by mass is more preferable, less than 0.01% by mass is particularly preferable, and it is most preferably not contained (below the detection limit).

In the embodiment (II) of the present invention, an antibacterial/bactericidal agent consisting only of the component (B) and the component (C2) can be used, and optional components of the composition for external use on the skin described later can be It can also be contained within a range that does not impair the effect. The suitable content is also the same as the content of the composition for external use on skin.

The antibacterial/bactericidal agent in the embodiment (II) of the present invention is applied to the skin in an appropriate amount (generally 0.1 to 0.5 g, although it depends on the application area), so that at least acne bacteria It is antibacterial and sterilizing, has little effect on Staphylococcus epidermidis, which is a resident skin bacterium, and can be used as a selective antibacterial and sterilizing agent. Furthermore, by using the component (C2) in combination, antibacterial and bactericidal effects against Staphylococcus aureus, which is a harmful Gram-positive bacterium, can be obtained, and it can be used as a multiple selective antibacterial and bactericidal agent. The antibacterial/bactericidal agent of the present invention can be used for selective antibacterial/bactericidal methods against P. acnes, P. acnes, and Staphylococcus aureus.

The selective antibacterial and bactericidal effects provide a moisturizing effect and a moisturizing experience. The reason for this is that it does not affect the growth of Staphylococcus epidermidis, which is a resident skin bacterium. Staphylococcus epidermidis breaks down sweat and sebum to produce fatty acids and glycerin. Fatty acids keep the skin slightly acidic and produce antibacterial peptides, which can prevent the growth of Staphylococcus aureus. Glycerin is a moisturizing ingredient that provides moisture to the skin and also plays a role in maintaining the skin barrier function. From the above, the antibacterial/bactericidal agent of the embodiment (II) of the present invention is suitable as an acne improving agent, a skin moisturizing agent, and an agent having both effects.

The pH of the antibacterial/bactericidal agent in the embodiment (II) of the present invention is preferably 4.5 or higher, more preferably 5.5 or higher, from the viewpoint of antibacterial/bactericidal performance. The upper limit of pH is preferably 10 or less, more preferably 9 or less from the viewpoint of skin irritation. The measurement of pH is based on the Japanese Pharmacopoeia 18th Edition, General Test Methods (measurement temperature: 25°C).

[Selective antibacterial/bactericidal composition for external use on the skin]
The antibacterial/bactericidal composition for external use against acne bacteria containing the antibacterial/bactericidal agent in the embodiment (II) of the present invention is suitable as a selective antibacterial/bactericidal composition for external use on the skin. The amount of the antibacterial/bactericidal agent in the composition for external use on skin is not particularly limited, and is appropriately selected. Suitable contents of components (B), (C2) and (D) in the composition for external use on the skin are the same as the contents of components (B), (C2) and (D) in the above antibacterial/bactericidal agent. are the same.

[Antibacterial/bactericidal external composition for skin against P. acnes]
The antibacterial/bactericidal composition for external use against acne bacteria containing an antibacterial/bactericidal agent according to the embodiment (II) of the present invention is suitable as an antibacterial/bactericidal composition for external use on the skin that selectively kills acne bacteria. The amount of the antibacterial/bactericidal agent in the composition for external use on skin is not particularly limited, and is appropriately selected. Preferred contents of components (B) and (C2) in the external composition for skin are the same as the preferred contents of components (B) and (C2) in the antibacterial/bactericidal agent. The content of component (D) can be appropriately set within a range that does not impair the effects of the invention, but from the viewpoint of not inhibiting the growth of Staphylococcus epidermidis, it is preferable It is preferable to make it the same as the content.

The formulation and properties of the antibacterial/bactericidal composition for external use on the skin against P. acnes are the same as the formulation and properties of the composition according to the embodiment (I) of the present invention. The external composition for skin of the present invention may contain various active ingredients used in pharmaceuticals, quasi-drugs, cosmetics, etc., if necessary, as long as the effects of the invention are not impaired. Those exemplified in the compositions that are embodiments of (I) can also be included. In addition, surfactants other than the component (C2) include those other than the component (C2) among the above components (C1).

The external composition for skin according to the embodiment (II) of the present invention can be obtained by mixing the above component (B), optionally component (C2), and optional components with water (the remainder).

Examples and comparative examples are shown below to specifically describe the present invention, but the present invention is not limited to the following examples. In the following examples, unless otherwise specified, "%" in the composition indicates mass %, and ratio indicates mass ratio.

[Example I, Comparative Example I]
A composition for external use (liquid formulation) was prepared by dissolving the components shown in the table below in purified water. The pH of the resulting composition for external use was measured based on the Japanese Pharmacopoeia 18th Edition/General Test Methods (measurement temperature: 25°C), and the following evaluations were performed. The results are also shown in the table.

[Antibacterial activity evaluation method] Inhibitory concentration (MIC) evaluation Using Staphylococcus epidermidis isolates, which are considered good bacteria, Staphylococcus aureus isolates, which are considered harmful bacteria, and opportunistic bacteria Cutibacterium acnes isolates Then, the antibacterial effect was evaluated by the microdilution method.
(1) Bacterial solution preparation A bacterial solution was prepared so that the initial number of bacteria of the following bacteria was 10 ⁷ cells/mL.
- (Skin opportunistic bacteria) Acne bacilli: Cutibacterium acnes, NBRC 107605
(harmful Gram-positive bacteria) Staphylococcus aureus: Staphylococcus aureus, NBRC 13276
- (Skin indigenous bacteria) Staphylococcus epidermidis: Staphylococcus epidermidis, NBRC 12993
All of the above three strains were obtained from National Institute of Technology and Evaluation (NBRC).
(2) Test Solution Compositions obtained in Example I and Comparative Example I (3) Test Method The test solution was serially diluted, and 100 μL of the bacterial solution prepared in (1) was inoculated into the diluted solution. Subsequently, Staphylococcus aureus and S. epidermidis were cultured at 32.5° C., and Acne bacilli at 37° C., and the results were determined after 24 to 48 hours.
(4) Judgment criteria <Decision criteria for positive growth>
When turbidity or a precipitate with a diameter of 1 mm or more is observed with the naked eye When two or more precipitates are observed even if the diameter of the precipitate is less than 1 mm <Decision criteria for negative growth>
When no turbidity or sedimentation is observed with the naked eye When there is only one sediment with a diameter of less than 1 mm The inhibitory concentration (MIC) for the test bacterium is the lowest concentration series that inhibits the growth of the test bacterium. Expressed as dilution concentration.
"-" indicates the positive growth in the compositions (undiluted) obtained in Examples and Comparative Examples.
<Antibacterial judgment criteria (inhibition circle)>
A disc containing the concentration of the test component calculated by the broth microdilution method was placed on the medium in which the test strain was seeded and cultured. The area where growth of the fungus was inhibited was observed as a circle (inhibition circle).
・No inhibition zone = no antibacterial properties (-)
・Presence of inhibition zone = presence of antibacterial properties (+)
<Determination criteria for positive growth>
3 points: Multiple selection antibacterial / sterilization Acne bacteria: Antibacterial (+), Staphylococcus aureus: Antibacterial (+), Staphylococcus epidermidis: No antibacterial (-)
2 points: Selective antibacterial / sterilization Acne bacteria: Antibacterial (+), Staphylococcus aureus: No antibacterial (-), Staphylococcus epidermidis: No antibacterial (-)
1 point: Selective antibacterial / no sterilization Acne bacteria: no antibacterial (-), or Staphylococcus epidermidis: antibacterial (+)

[Sustained moist feeling (moisturizing feeling)]
After taking a bath before going to bed, a professional evaluator took 0.5 g of the sample (external preparation composition) on the hand, rubbed it on the face, and evaluated the moist feeling of the hands the next morning. The results were sensory-evaluated by 5 expert panels, and based on the average of the scores, the evaluation criteria below were used.
<Evaluation Criteria for Sustained Moisture>
5 points: strong moist feeling 4 points: moist feeling 3 points: slightly moist feeling 2 points: not much moist feeling 1 point: no moist feeling
A: Average score of 4.0 to 5.0 B: Average score of 3.0 to less than 4.0 C: Average score of 2.0 to less than 3.0 D: Average score less than 2.0 points A and B are acceptable.

The raw materials used in the above examples are shown below. In addition, unless otherwise specified, the amount of each component in the table is the amount in terms of pure content. In addition, the descriptions of "Japanese Pharmacopoeia", "Regulations", "Pharmaceutical Additives", and "External Regulations" below refer to the 18th revision of the Japanese Pharmacopoeia Standards, Japanese Non-Pharmacopoeia Pharmaceutical Standards, and pharmaceutical excipients, respectively. It means that it is a raw material that meets the standards (2018) and the standards for quasi-drug raw materials (2021).
・Isopropyl methylphenol: Standards of External Standards, Isopropyl methylphenol, manufactured by Osaka Kasei Co., Ltd. ・Panthenol: Standards of Standards of External Standards, D-pantothenyl alcohol, manufactured by DSM Co., Ltd. ・Polyethylene glycol monolaurate (10EO): Standards of Standards of External Standards , NIKKOL MYL-10, manufactured by Nikko Chemicals Co., Ltd., HLB = 12.5
・Polyethylene glycol monooleate (10EO): Japanese Standards, NIKKOL MYO-10V, Nikko Chemicals Co., Ltd., HLB=11.0
・Polyethylene glycol monostearate (10EO): Japanese Standards, NIKKOL MYS-10V, manufactured by Nikko Chemicals Co., Ltd., HLB=11.0
- Tetraoleic acid polyoxyethylene sorbitol (30EO): Japanese Standards, NIKKOL GO-430NV, HLB = 11.5
- Tetraoleic acid polyoxyethylene sorbitol (40EO): Japanese Standards, NIKKOL GO-440V, manufactured by Nikko Chemicals Co., Ltd., HLB = 12.5
- Polyoxyethylene sorbitol tetraoleate (60EO): Standards of External Genesis, NIKKOL GO-460V, manufactured by Nikko Chemicals Co., Ltd., HLB = 14.0
・Decaglyceryl monomyristate: Japanese Standards, NIKKOL Decaglyn 1-M, manufactured by Nikko Chemicals Co., Ltd., HLB = 14.0
・Polyoxyethylene (9) lauryl ether: Japanese Standard, NIKKOL BL-9EX, manufactured by Nikko Chemicals Co., Ltd., HLB = 14.5
- Polyoxyethylene lauryl ether (25EO): NIKKOL BL-25, manufactured by Nikko Chemicals Co., Ltd., HLB = 19.5
・Polyethylene glycol distearate (150EO): Japanese Standards, NIKKOL CDS-6000P, manufactured by Nikko Chemicals Co., Ltd., HLB=16.5

[Example II, Comparative Example II]
The ingredients shown in the table below were dissolved in purified water to prepare external skin compositions (solutions). The pH of the resulting external composition for skin was measured according to the 18th revision of the Japanese Pharmacopoeia General Test Methods (measurement temperature: 25°C), and the following evaluations were performed.

[Method for evaluating antibacterial activity] Evaluation of inhibitory concentration (MIC) Evaluation was performed in the same manner as in [Method for evaluating antibacterial activity] in Example I and Comparative Example I above, except that the test solution was changed as follows.
(2) Test solution Panthenol, polyethylene glycol monolaurate (10EO), a mixture of panthenol and polyethylene glycol monolaurate (10EO) (1:1.5), and the compositions obtained in Example II and Comparative Example II.

Figures 1 to 3 show dual minimum inhibitory concentration diagrams for the panthenol, polyethylene glycol monolaurate (10EO), and the mixture of panthenol and polyethylene glycol monolaurate (10EO) (1:1.5). As shown in the figure, (B) panthenol and (C2) polyethylene glycol (10EO) monolaurate (PEG (10EO) monolaurate) alone, and the MIC of the mixture of components (B) and (C2) The results were plotted on a graph, the MIC of the (B) component alone and the MIC of the (C2) component alone were connected by a line, and the position of the MIC of the mixture on this line was examined. For P. acnes and Staphylococcus aureus, the MIC of the mixture is located inside the line, and it can be seen that the combined use of the (B) component and the (C2) component enhances the antibacterial activity. On the other hand, for Staphylococcus epidermidis, the MIC of the mixture is located outside the above line. It was confirmed that the growth was not inhibited.

As in Example I and Comparative Example I above, <determination criteria for positive growth> were described.
In the same manner as in Example I and Comparative Example I, [durability of moist feeling (moisturizing sensation)] was evaluated.

A face wash (Table III-1) and a lotion (Table III-2) having the following compositions in embodiments (I) and (II) were prepared by a conventional method (formulation examples 1 to 4). All of them had multiple selective antibacterial and bactericidal actions, and were also excellent in the moist feeling lasting effect.

The raw materials used in preparing Example II and Comparative Example II, as well as the Formulation Examples are shown below. Note that descriptions of the same items as in Example I and Comparative Example II are omitted.
・Polyoxyethylene sorbitol monolaurate (6EO): Japanese Standards, NIKKOL GL-1, manufactured by Nikko Chemicals Co., Ltd., HLB = 15.5
・Sorbitan monolaurate (also known as coconut oil fatty acid sorbitan): Japanese Standards, NIKKOL SL-10, manufactured by Nikko Chemicals Co., Ltd., HLB = 8.5
・Polyoxyethylene (20) sorbitan monooleate: Standards of Japanese Standards, NIKKOL TO-10V, manufactured by Nikko Chemicals Co., Ltd., HLB = 15.0
· Polyglyceryl monolaurate-10: Japanese Standards, NIKKOL Decaglyn 1-L, manufactured by Nikko Chemicals Co., Ltd., HLB = 15.5
・Dipotassium Glycyrrhizinate: Japanese Standards, Dipotassium Glycyrrhizinate, manufactured by Maruzen Pharmaceutical Co., Ltd. ・Natural Vitamin E: Japanese Standards, Emix-D, manufactured by Tama Biochemical Co., Ltd. ・Phosphate L-ascorbic acid Magnesium: Kangenki, NIKKOL VC-PMG, Nippon Surfactant Kogyo Co., Ltd. Soybean extract: Kangenki, flavosterone SB, Ichimaru Farcos Co., Ltd. Olive oil: Kangenki, NIKKOL olive oil, Nikko Chemicals Co., Ltd.・Myristic acid: Japanese Standards, LUNAC MY-98, Kao Corporation ・Isostearic acid: Japanese Standards, Isstearic Acid EX, KOKYU ALCOHOL KOGYO Co., Ltd. ・Palmitic acid: Japanese Standards, LUNAC P-95 , Kao Co., Ltd. Concentrated glycerin: Japanese Standards, Concentrated glycerin for cosmetics, Sakamoto Yakuhin Kogyo Co., Ltd. Sorbit liquid: Japanese Standards, Sorbit L-70, Mitsubishi Shoji Food Tech Co., Ltd. Dipropylene Glycol: Standards for Chemicals, Dipropylene Glycol DPG-FC, manufactured by Asahi Glass Co., Ltd. N-coconut oil fatty acid acyl-DL-alanine triethanolamine liquid: Standards for Standards for Chemicals, Amilite ACT-12, manufactured by Ajinomoto Co., Inc., water Potassium oxide: Kangenki, potassium hydroxide, manufactured by Junsei Chemical Co., Ltd. Lauric acid diethanolamide: Kangenki, Stahome DL, manufactured by NOF Co., Ltd. Polyethylene glycol 1500: Kangenki, PEG-1500, Manufactured by Sanyo Chemical Industries Co., Ltd. Ethylene glycol distearate: Japanese Standards, NIKKOL PEARL-1222, Nippon Surfactant Kogyo Co., Ltd. Disodium edetate: Japanese Pharmacopoeia, sodium edetate Chubu Chilest Co., Ltd. Manufactured by paraoxybenzox Methyl acid: Regulations of External Harmony, methyl paraoxybenzoate, manufactured by Ueno Pharmaceutical Co., Ltd. Propyl parahydroxybenzoate: Regulations of External Harmony, Mekkins P, manufactured by Ueno Pharmaceutical Co., Ltd. Fragrance: JP 2002-128658, paragraph [ 0065] to [0071], A to E described in JP-A-2003-73249, or 1 to 4 described in Japanese Patent Application No. 2019-023940 [0016] to [0023] as appropriate To be elected.
・Tocopherol acetate: Japanese Pharmacopoeia, manufactured by DSM Co., Ltd. ・1,3-butylene glycol: Standards of Japanese Standards, 1,3-butylene glycol, manufactured by Daicel Chemical Industries, Ltd. ・Trimethylglycine: Standards of Standards of Standards, Aminocoat, Asahi Kasei Co., Ltd. Polyoxyethylene hydrogenated castor oil (60EO): External Gen., NIKKOL HCO-60, Nippon Surfactant Kogyo Co., Ltd. Sodium citrate: External Gen., trisodium citrate, Showa Kako Co., Ltd. ) Sodium hyaluronate: Sodium hyaluronate, sodium hyaluronate SF20, manufactured by Mitsui Chemicals Fine Co., Ltd. Xanthan gum: Specified outside original, Labor Gum (registered trademark) GS-C, DSP Gokyo Food & Chemical Co., Ltd. Hydroxyethyl cellulose: Japanese Standards, HEC Daicel EE-820, manufactured by Daicel Finechem Co., Ltd. ・l-menthol: Japanese Standards, l-menthol, Takasago Perfumery Co., Ltd. ・Lavender oil: Standards of Standards, lavender oil, fragrance Manufactured by Sakae Kogyo Co., Ltd. ・Peppermint oil: Standards for External Harmony, Peppermint oil, Manufactured by Koei Kogyo Co., Ltd. ・Eucalyptus oil: Standards for Standards for Standards, eucalyptus oil, manufactured by PAYAN BERTRAND

Claims

An external composition for acne, comprising (A) isopropylmethylphenol and one or more components selected from the following components (B) and (C1).
(B) one or more selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenyl ethyl ether (C1) polyethylene glycol having an HLB of less than 15.0 and a fatty acid chain length of 12 to 18 One or more selected from fatty acid esters, polyoxyethylene sorbitol fatty acid esters, sorbitan fatty acid esters, polyglycerin fatty acid esters, and polyoxyethylene alkyl ethers having an alkyl chain length of 12 to 18
The composition for external use for acne according to claim 1, wherein the content of component (A) is 0.01 to 0.3% by mass.
The composition for external use for acne according to claim 1 or 2, wherein the total content mass ratio of the component (B) and the component (C1) to the content of the component (A) is 1-350.
The external composition for acne according to claim 1 or 2, comprising the (A) component, the (B) component, and the (C1) component.
(A) isopropylmethylphenol and one or more components selected from the following components (B) and (C1): acnes-selective antibacterial/sterilizing composition for external use.
(B) one or more selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenyl ethyl ether (C1) polyethylene glycol having an HLB of less than 15.0 and a fatty acid chain length of 12 to 18 One or more selected from fatty acid esters, polyoxyethylene sorbitol fatty acid esters, sorbitan fatty acid esters, polyglycerin fatty acid esters, and polyoxyethylene alkyl ethers having an alkyl chain length of 12 to 18
The composition for external use for selective antibacterial and sterilizing acne bacteria according to claim 5, which is antibacterial and sterilizing against P. acnes and Staphylococcus aureus, but not antibacterial and sterilizing against Staphylococcus epidermidis.
The composition for external use for acne bacteria-selective antibacterial and sterilization according to claim 5 or 6, containing the component (A), the component (B), and the component (C1).
(B) An antibacterial/bactericidal agent against P. acnes, containing as an active ingredient one or more selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol, and pantothenyl ethyl ether.
Furthermore, (C2) polyethylene glycol fatty acid esters, polyoxyethylene sorbit fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters and polyglycerin fatty acid esters having a fatty acid chain length of 12 to 18, and alkyl chain lengths of 12 to 18. The antibacterial/bactericidal agent according to claim 8, containing one or more selected from polyoxyethylene alkyl ethers.
The antibacterial/bacterial agent according to claim 8, which is a selective antibacterial/bacterial agent.
The selective antibacterial/bactericidal agent according to claim 9, which is antibacterial/bacterial against P. acnes and Staphylococcus aureus, but not antibacterial/bacterial against Staphylococcus epidermidis.
The antibacterial/bactericidal agent according to claim 9, wherein the (C2) component has an HLB of 10 to 18.
The antibacterial/bactericidal agent according to claim 9, wherein the content mass ratio represented by (C2)/(B) is 0.03 to 40.
(D) hydrogen peroxide, sodium hypochlorite, ethanol, isopropanol, ovanol, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, cresol, popillon iodine, iodine, sodium dichloroisocyanurate, chlorhexidine and acrinol, and ( A) The antibacterial/bactericidal agent according to claim 8, wherein the content of isopropylmethylphenol is 0.3% by mass or less.
An antibacterial/bactericidal composition for external use against acne bacteria, containing the antibacterial/bactericidal agent according to any one of claims 8 to 14.