Skin external composition

Abstract

To provide a skin external composition which is an O / W emulsion having selective antibacterial and bactericidal properties, suppressed oil-water separation, suppressed skin irritation and an excellent moisturizing sensation.SOLUTION: There is provided a skin external composition which is an O / W emulsion and comprises (A) one or more selected from pantothenic acid or the like, (B) one or more surfactants which are selected from a polyethylene glycol fatty acid ester, a polyoxyethylene sorbitol fatty acid ester, a sorbitan fatty acid ester, a polyglycerol fatty acid ester, a polyoxyethylene glycerol fatty acid ester and a polyoxyethylene alkyl ether and have an HLB of 8 to 16 and (C) one or more selected from N-myristoyl-L-glutamate, N-stearoyl-L-glutamate, myristoyl methyl taurate, N-stearoyl-N-methyl taurate and stearoyl lactate.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a composition for external use on the skin that selectively antibacterial and bactericidal against acne bacteria in particular.

Background Art

[0002] In the skin of healthy people, as skin commensal bacteria, Staphylococcus epidermidis and acne bacteria exist and play a role in maintaining the homeostasis of the skin. Staphylococcus epidermidis is known as a beneficial commensal bacterium because it has the functions of enhancing the skin barrier function, maintaining the moisturizing function, and antibacterial action against pathogenic bacteria. On the other hand, acne bacteria are known to proliferate excessively due to clogging of pores and excessive secretion of sebum, and cause inflammation and other problems due to the fatty acids produced, which is the cause of acne. In acne treatment, acne bacteria are sterilized with bactericidal agents such as benzalkonium chloride having a bactericidal effect, and inflammation is suppressed with anti-inflammatory agents such as dipotassium glycyrrhizinate. In addition to the growth of acne bacteria, dry skin is also known as a cause of acne. When the skin is dry, sebum secretion becomes excessive, pores are easily clogged, and acne is easily induced. Therefore, it has been found that moisturizing is important in order to obtain a sufficient therapeutic effect against acne. Furthermore, in dry skin, the ratio of Staphylococcus epidermidis to acne bacteria is reduced, so that sufficient therapeutic effects may not be obtained against skin diseases such as dryness and acne caused by dryness with only anti-inflammatory components.

[0003] On the other hand, the present applicant has found that when pantothenic acid or the like is used in combination with a specific nonionic surfactant, it has an excellent antibacterial and bactericidal effect against acne bacteria, which are the causative bacteria of acne, and in particular, it has an excellent antibacterial and bactericidal effect against acne bacteria and exhibits selective antibacterial properties without inhibiting the growth of Staphylococcus epidermidis (Patent Document 1).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, it has been found that when pantothenic acid or the like is used in combination with a specific nonionic surfactant and formulated into an O / W emulsion having excellent moisturizing power, oil-water separation occurs. The present invention has been made in view of the above circumstances, and an object thereof is to provide a topical skin composition which is an O / W emulsion having the above-described selective antibacterial and bactericidal properties, in which oil-water separation is suppressed, skin irritation is suppressed, and the moisturizing feeling is excellent.

Means for Solving the Problems

[0006] As a result of intensive studies to achieve the above object, the present inventors have found that by adding (C) at least one selected from N-myristoyl-L-glutamate, N-stearoyl-L-glutamate, myristoyl methyl taurine salt, N-stearoyl-N-methyl taurine salt and stearoyl lactate to an O / W emulsion in which (A) pantothenic acid or the like and (B) a specific nonionic surfactant are used in combination, an O / W emulsion having the above-described selective antibacterial property, in which oil-water separation is suppressed, skin irritation is further suppressed, and the moisturizing feeling is excellent, can be provided, and thus the present invention has been completed.

[0007] Therefore, the present invention provides the following topical skin composition. 1. (A) At least one selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol and pantothenyl ethyl ether, (B) At least one surfactant selected from polyethylene glycol fatty acid esters, polyoxyethylene sorbitol fatty acid esters, sorbitan fatty acid esters, polyglycerol fatty acid esters and polyoxyethylene glycerol fatty acid esters having a fatty acid chain length of 12 to 18, and polyoxyethylene alkyl ethers having an alkyl chain length of 12 to 18 and an HLB of 8 to 16, and (C) One or more selected from N-myristoyl-L-glutamate, N-stearoyl-L-glutamate, myristoylmethyl taurine salt, N-stearoyl-N-methyl taurine salt, and stearoyl lactate, A topical skin composition containing the same and being an O / W emulsion. 2. The topical skin composition according to item 1, wherein the component (B) is one or more selected from polyethylene glycol fatty acid esters, polyoxyethylene sorbitol fatty acid esters, sorbitan fatty acid esters, and polyoxyethylene glycerin fatty acid esters having a fatty acid chain length of 12 to 14, and polyoxyethylene alkyl ethers having an alkyl chain length of 12 to 14. 3. The topical skin composition according to item 1 or 2, wherein the content of the component (C) is 0.01 to 3% by mass. 4. The topical skin composition according to any one of items 1 to 3, further containing one or more selected from (D) ester oil, hydrocarbon oil, and silicone oil. 5. The topical skin composition according to item 4, wherein the mass ratio (C) / (D) of the component (C) to the component (D) is 0.0008 to 0.35. 6. The topical skin composition according to item 4 or 5, wherein the mass ratio [(A)+(B)] / (D) of the total of the components (A) and (B) to the component (D) is 0.025 to 0.6. 7. The topical skin composition according to any one of items 1 to 6, which is for acne treatment or prevention.

Effect of the Invention

[0008] According to the present invention, it is possible to provide a topical skin composition which is an O / W emulsion having the above selective antibacterial and bactericidal properties, suppressing oil-water separation, suppressing skin irritation, and excellent in moisturizing feeling.

Mode for Carrying Out the Invention

[0009] Hereinafter, the present invention will be described in detail. [Component (A)] Component (A) 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 alone or in combination of two or more. Component (A) has an excellent antibacterial and bactericidal effect against acne bacteria and does not inhibit the growth of Staphylococcus epidermidis, and these components have such a selective antibacterial and bactericidal effect.

[0010] From the viewpoint of effect, panthenol and pantothenyl ethyl ether are preferred as component (A). Panthenol, which is a water-soluble vitamin, is known to have anti-inflammatory effects, activation of skin cells, enhancement of skin elasticity and water retention, etc.

[0011] Panthenol and salts of pantothenic acid such as calcium pantothenate and sodium pantothenate are converted into pantothenic acid inside the skin and exhibit the above-mentioned pharmacological effects. Pantothenyl ethyl ether is an ethyl ether of panthenol and, like panthenol, changes into pantothenic acid in the body.

[0012] From the point of having a more antibacterial and bactericidal effect against acne bacteria, the content of component (A) is preferably 0.1% by mass or more in the skin external composition, and from the point of not more inhibiting the growth of Staphylococcus epidermidis, it is preferably 2% by mass or less, and more preferably 0.3 - 2% by mass.

[0013] [Component (B)] Component (B) of the present invention is one or more surfactants selected from polyethylene glycol fatty acid esters, polyoxyethylene sorbitol fatty acid esters, sorbitan fatty acid esters, polyglycerol fatty acid esters, and polyoxyethylene glycerol fatty acid esters with a fatty acid chain length of 12 - 18, and polyoxyethylene alkyl ethers with an alkyl chain length of 12 - 18, and having an HLB of 8 - 16, and two or more of them may be used in combination.

[0014] (B) component has a fatty acid chain length or an alkyl chain length of 12 to 18, preferably 12 to 14, and more preferably 12. By setting such a fatty acid chain length or alkyl chain length, the antibacterial and bactericidal effects against acne bacteria are further improved. In particular, when the carbon chain length or alkyl chain length is 12, the combined use of component (A) and component (B) makes it easier to obtain antibacterial and bactericidal effects against acne bacteria. The number of moles of ethylene oxide added is preferably 6 to 60, more preferably 6 to 55, still more preferably 6 to 40, particularly preferably 6 to 25, and most preferably 10. By setting the range of the above upper and lower limits, it is possible to maximize the selective antibacterial and bactericidal power that can antibacterial and bactericidal against acne bacteria and not antibacterial and bactericidal against Staphylococcus epidermidis. Furthermore, from the viewpoint of easily obtaining an excellent antibacterial and bactericidal effect against acne bacteria, monoesters are preferred, and those in a liquid state at normal temperature (25 ° C) are preferred.

[0015] (B) component has an HLB (Hydrophile-Lipophile Balance) of 8 to 16, more preferably 15 or less, and still more preferably 10 to 13. By setting the range as above, it becomes easier to interact with the cell wall and cell membrane of bacteria, so that an excellent antibacterial and bactericidal effect against acne bacteria is more easily obtained. HLB is an index of the affinity for water and oil. Generally, the closer to 0, the higher the lipophilicity, and the closer to 20, the higher the hydrophilicity. HLB can be calculated by any of the Atlas method, Griffin method, Davis method, Kawakami method, etc., and also, as a product, the value published by the manufacturer can be taken into consideration. The HLB in this specification is calculated based on the actual measurement of the HLB value by the emulsification method described on pages 854-855 of the "Handbook - Cosmetics and Formulation Raw Materials - Revised Edition", published by Nikko Chemicals Co., Ltd. on February 1, 1977. As a specific method for obtaining the HLB value, component (C) is combined with sorbitan monostearate (NIKKOL SS-10, HLB 4.7) as a standard substance of the emulsifier, and the total amount of these two emulsifiers is made constant. Only the ratio is changed to emulsify liquid paraffin (HLB 10.1), which is the emulsion, and after standing for 24 hours, the optimal ratio of the stable emulsifier is determined from the cream separation amount, turbidity, and lower layer water separation, etc. The HLB value x of component (C) is calculated by the following formula (1). y = (x × usage (mass%) + z × usage (mass%)) / 100 ··· Equation (1) Here, in the above Equation (1), "x" represents the HLB value of the component (C), "y" represents the HLB value of liquid paraffin, and "z" represents the HLB value of sorbitan monostearate (NIKKOL SS-10). Note that the HLB value of the liquid paraffin can be determined in the same manner by combining sorbitan monostearate (NIKKOL SS-10, HLB 4.7) and polyoxyethylene sorbitan monostearate (NIKKOL TS-10, HLB 14.9).

[0016] Examples of each component with an HLB of 8 to 16 include the following. Examples of polyethylene glycol fatty acid esters with a fatty acid chain length of 12 to 18 include polyethylene glycol monolaurate (10EO), polyethylene glycol monooleate (10EO), polyethylene glycol monooleate (6EO), polyethylene glycol monostearate (10EO), etc. The numerical values in parentheses in the notations of the above-exemplified polyethylene glycol fatty acid esters 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 alkyl ethers, and polyoxyethylene glycerin fatty acid esters.

[0017] Examples of polyoxyethylene sorbitol fatty acid esters with 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), polyoxyethylene sorbitol monolaurate (6EO), etc.

[0018] As sorbitan fatty acid esters with a fatty acid chain length of 12 to 18, a fatty acid chain length of 12 is preferred, and a monoester is preferred. Specifically, sorbitan monolaurate and the like can be mentioned.

[0019] As polyglycerol fatty acid esters with a fatty acid chain length of 12 to 18, decaglyceryl monomyristate, polyglyceryl-10 monostearate, polyglyceryl-10 monooleate and the like can be mentioned. The numerical value at the end in the notation of the polyglycerol fatty acid esters exemplified above represents the average degree of polymerization of glycerol.

[0020] As polyoxyethylene glycerol fatty acid esters with a fatty acid chain length of 12 to 18, polyoxyethylene glyceryl trioleate (20 EO), polyoxyethylene glyceryl monostearate (15 EO), polyoxyethylene glyceryl monolaurate (9 EO) and the like can be mentioned.

[0021] As polyoxyethylene alkyl ethers with an alkyl chain length of 12 to 18, lauromacrogols such as polyoxyethylene(4) lauryl ether, polyoxyethylene(9) lauryl ether, polyoxyethylene(10) lauryl ether, polyoxyethylene(15) lauryl ether, polyoxyethylene(20) lauryl ether; polyoxyethylene(10) cetyl ether, polyoxyethylene(10) oleyl ether and the like can be mentioned.

[0022] Among them, one or more selected from polyethylene glycol saturated fatty acid esters, polyoxyethylene sorbitol fatty acid esters, sorbitan fatty acid esters, and polyoxyethylene glycerin fatty acid esters having a fatty acid chain length of 12 to 14, and polyoxyethylene alkyl ethers having an alkyl chain length of 12 to 14 are preferable. Specifically, polyethylene glycol monolaurate (10 EO), polyoxyethylene sorbitol monolaurate (6 EO), polyoxyethylene glyceryl monolaurate (9 EO), polyoxyethylene lauryl ether (10), polyoxyethylene lauryl ether (15), and polyoxyethylene lauryl ether (20) are more preferable.

[0023] The content of component (B) is preferably 0.1% by mass or more in the skin external composition from the viewpoint of having a more antibacterial and bactericidal effect against acne bacteria and Staphylococcus aureus, and preferably 10% by mass or less from the viewpoint of not more inhibiting the growth of Staphylococcus epidermidis, more preferably 0.2 to 6% by mass, and even more preferably 0.7 to 3% by mass. In addition, by the combined use of component (A) and component (B), a bactericidal effect can be obtained even below the MIC.

[0024] [Component (C)] Component (C) of the present invention is one or more selected from N-myristoyl-L-glutamate, N-stearoyl-L-glutamate, myristoyl methyl taurine salt, N-stearoyl-N-methyl taurine salt, and stearoyl lactate, and two kinds may be used in combination. Examples of the salt include triethanolamine salt, potassium salt, and sodium salt, and the sodium salt is preferable. By using such an anionic surfactant in an O / W type emulsion in which (A) pantothenic acid or the like and (B) a specific nonionic surfactant are used in combination, the above-mentioned selective antibacterial and bactericidal properties are obtained, oil-water separation is suppressed, and a moisturizing feeling can be further obtained. As component (C), N-stearoyl-N-methyl taurine salt, N-stearoyl-L-glutamate, and stearoyl lactate are preferable.

[0025] The content of component (C) is preferably 0.01% by mass or more in the skin external composition from the viewpoint of further improving the oil-water separation stability, preferably 3% by mass or less from the viewpoint of further suppressing irritation to the skin, more preferably 0.05 to 2.5% by mass, and even more preferably 0.1 to 2% by mass.

[0026] [Component (D)] The skin external composition of the present invention preferably further contains at least one selected from (D) ester oil, hydrocarbon oil, and silicone oil from the viewpoints of selective antibacterial and bactericidal power, suppression of oil-water separation, and moisturizing feeling, and two or more kinds of component (D) may be used in combination. Further, by blending component (D), a skin external composition excellent in appearance can be obtained. Among them, hydrocarbon oils such as petrolatum, paraffin, liquid paraffin, liquid isoparaffin, squalane, ceresin, gelled hydrocarbon, and microcrystalline wax; fatty acid ester oils such as tri-2-ethylhexyl glycerin, isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, and diisopropyl adipate; polyhydric alcohol fatty acid esters such as glyceryl triisooctanoate and glyceryl tri(caprylic / capric acid), and silicone oils such as methylpolysiloxane (dimethylpolysiloxane) can be mentioned. Among these, from the viewpoint of more exerting the above-mentioned blending purposes and effects, liquid isoparaffin, tri-2-ethylhexyl glycerin, and methylpolysiloxane are preferable.

[0027] The content of component (D) is preferably 0.5% by mass or more in the skin external composition from the viewpoints of selective antibacterial and bactericidal power and moisturizing feeling, and preferably 20% by mass or less from the viewpoint of suppressing oil-water separation. More preferably 2 to 12.5% by mass, and even more preferably 5 to 12.5% by mass.

[0028] The mass ratio (C) / (D) of the content of the component (C) to the component (D) is preferably 0.0008 or more from the viewpoint of improving the oil-water separation stability, preferably 0.35 or less, more preferably 0.004 to 0.27, and even more preferably 0.008 to 0.2 from the viewpoints of improving the oil-water separation stability and further suppressing the irritation feeling to the skin. By setting it to be not less than the above lower limit value, oil-water separation is more suppressed. By setting it to be not more than the above upper limit value, a skin external preparation which is an O / W type emulsion with more suppressed skin irritation and more excellent moisturizing feeling can be obtained. Further, by setting it within the above range, more selective antibacterial and bactericidal properties can be obtained.

[0029] The mass ratio [(A)+(B)] / (D) of the total content of the components (A) and (B) to the component (D) is preferably 0.025 or more from the viewpoint of more easily obtaining a bactericidal and antibacterial effect against acne bacteria, preferably 0.6 or less, more preferably 0.08 to 0.4, from the viewpoints of more difficultly inhibiting the growth of Staphylococcus epidermidis and further suppressing skin irritation.

[0030] The skin external composition of the present invention is an O / W type emulsion, and as long as it is an O / W type emulsion, it may be in any form such as liquid, solid, semi-solid (gel-like, ointment-like, paste-like, foamy), etc. Further, the embodiment may be in any form such as a skin external pharmaceutical, a skin external quasi-drug, a cosmetic, a skin cleansing agent (facial wash, etc.). The dosage form of the skin external composition is not particularly limited, and examples thereof include an ointment, a cream, a gel, an emulsion, a spray agent that sprays in a foamy form, an aerosol agent that sprays in a foamy or paste-like form, an ointment, a pack agent, a body shampoo, a hair shampoo, a facial wash, etc. Among them, a cream and an emulsion are preferable. By using an O / W type emulsion, the skin moisturizing power is improved. In addition, for those that are not O / W type emulsions, for example, aqueous lotions, etc., the skin moisturizing power is insufficient compared to O / W type emulsions, and there are also no problems with oil-water separation stability.

[0031] [Skin external composition] The topical skin composition of the present invention is an antibacterial and bactericidal agent having an excellent antibacterial and bactericidal effect against Propionibacterium acnes, which is the causative bacterium of acne. In particular, it has an excellent antibacterial and bactericidal effect against Propionibacterium acnes and does not inhibit the growth of Staphylococcus epidermidis. Because of its selective antibacterial property, it is suitable as a topical skin composition for the treatment or prevention of acne, for skin moisturization, or for both effects, and as a topical skin composition for selective antibacterial and bactericidal treatment of Propionibacterium acnes. The topical skin composition of the present invention prevents dryness by improving the health of the skin flora, and in addition, the skin is moisturized by the component (D) contained therein. Therefore, it is particularly suitable for the treatment or prevention of acne caused by skin dryness, for killing and antibacterial against Propionibacterium acnes, which is the causative bacterium of acne, and for preventing skin dryness caused by selective antibacterial effect that does not antibacterialize Staphylococcus epidermidis that prevents skin dryness.

[0032] The topical skin composition of the present invention, in an appropriate amount (although it depends on the area to be applied, generally 0.1 to 0.75 g [solid or semi-solid preparations such as creams and gels], 1 to 5 mL [liquid preparations such as emulsions] are applied to the skin), can at least antibacterial and bactericidal to acne bacteria, and has a low impact on the growth of Staphylococcus epidermidis, which is a skin commensal bacterium. Preferably, it has a high antibacterial and bactericidal activity against acne bacteria. Also, acne bacteria are selectively antibacterial and bactericidal, and have a low impact on the growth of Staphylococcus epidermidis, which is a skin commensal bacterium. The composition of the present invention can be used as a topical skin medicine having effects and efficacy such as acne, eruptions, xeroderma, dry skin in children, rough fingers, cracks in hands and feet, erythema, keratosis of elbows, knees, heels and ankles, heat rash (excluding sagging), swelling and tightness of the skin after wounds and burns (excluding the face), itching, eczema, dermatitis, inflammation, urticaria, miliaria, insect bites, etc., and can prevent skin roughness, roughness, miliaria, cracks, erythema, acne, prevent oily skin, prevent razor burn, prevent sunburn and freckles, prevent flushing after sunburn and snowburn, tighten the skin, clean the skin, improve the skin, keep the skin healthy, moisturize the skin, protect the skin, prevent skin dryness, etc. It can be used as quasi-drugs. It can also be used in cosmetics having effects and efficacy such as cleaning the skin, preventing acne and miliaria, improving the skin, improving the texture of the skin, keeping the skin healthy, preventing skin roughness, moisturizing the skin, supplementing and maintaining the moisture and oil content of the skin, maintaining the flexibility of the skin, protecting the skin, preventing skin dryness, softening the skin, firming the skin, and smoothing the skin. Among these, it is suitable as a topical skin composition for acne prevention, acne treatment, and acne symptom improvement, and a topical skin composition for moisturization. It is also suitable as a topical skin composition for selective antibacterial and bactericidal against acne bacteria with a low impact on the growth of Staphylococcus epidermidis. The criteria for judging "antibacterial activity" and "selective antibacterial activity" shall be based on the examples described later.

[0033] In particular, in the case of a topical skin composition for selectively antibacterial and bactericidal action against acne bacteria, from the viewpoint of reducing the influence on the growth of Staphylococcus epidermidis, hydrogen peroxide, sodium hypochlorite, isopropanol, obanole, cetylpyridinium chloride, cresol, povidone iodine, iodine, sodium dichloroisocyanurate, and acrinol are preferably not substantially (at effective concentrations) contained. Not substantially contained means less than 0.3% by mass with respect to the composition, more preferably less than 0.1% by mass, still more preferably less than 0.01% by mass, and particularly preferably not contained (below the detection limit).

[0034] By having a selective antibacterial and bactericidal effect and further containing the component (D), it has a more moisturizing effect and a better moisturizing feeling can be obtained. The reason is that it does not affect the growth of Staphylococcus epidermidis, which is a skin commensal bacterium. Staphylococcus epidermidis decomposes sweat and sebum to produce fatty acids and glycerin. Fatty acids keep the skin weakly acidic and can prevent the growth of Staphylococcus aureus by producing antibacterial peptides. Glycerin is a moisturizing component that gives moisture to the skin and also plays a role in maintaining the skin barrier function, so a moisturizing feeling can be obtained.

[0035] From the viewpoint of antibacterial and bactericidal performance, the pH of the antibacterial and bactericidal agent of the present invention is preferably 4 or more, more preferably 4.5 or more. The upper limit of the pH is preferably 10 or less, more preferably 9 or less, from the viewpoint of skin irritation. The pH is measured according to the 18th revised Japanese Pharmacopoeia, general test method (measurement temperature: 25°C).

[0036] The topical skin composition of the present invention may contain various active ingredients used in pharmaceuticals, quasi-drugs, cosmetics, etc., as long as the effects of the invention are not impaired as necessary. For example, anti-inflammatory agents, antihistamines, bactericides, antipruritics, wound healing agents, local anesthetics, blood vessel repair agents, keratolytics, vitamins (excluding component (A)), surfactants (excluding components (B) and (C)), cooling agents, moisturizing agents, and amino acids, etc. can be contained, and the following components are exemplified. It can also contain water as the remainder.

[0037] Examples of anti-inflammatory agents include, for example, tranexamic acid, glycyrrhetinic acid, glycyrrhizic acid or pharmaceutically acceptable derivatives thereof and their salts (e.g., dipotassium glycyrrhizinate), licorice extract, steroid compounds (hydrocortisone, prednisolone, methylprednisolone, clobetasone, betamethasone, dexamethasone, cortisone, flumethasone, beclomethasone, fluticasone or pharmaceutically acceptable derivatives thereof), indomethacin, ibuprofen, ibuprofen piconol, bufexamac, ufenamate, piroxicam, ketoprofen, salicylic acid or pharmaceutically acceptable derivatives thereof and their salts, dimethylisopropylazulene, toki extract, shikon extract, etc.

[0038] Examples of antihistamines include diphenhydramine, chlorpheniramine, mequitazine, azelastine, emedastine, ketotifen or pharmaceutically acceptable derivatives thereof and their salts, etc. Preferably, diphenhydramine hydrochloride and chlorpheniramine maleate are mentioned.

[0039] Examples of bactericides include isopropylmethylphenol, benzethonium chloride, benzalkonium chloride, chlorhexidine hydrochloride, hinokitiol, etc. When these bactericides are formulated, the amount is preferably 0.01 to 0.3% by mass, more preferably 0.03 to 0.3% by mass in the topical skin composition from the viewpoints of having a higher antibacterial and bactericidal effect against acne bacteria and not inhibiting the growth of Staphylococcus epidermidis.

[0040] Examples of antipruritics include nonylvanillylamide, capsaicin, benzyl nicotinate, capsicum tincture, etc. Examples of wound healing agents include allantoin, zinc oxide, etc. Examples of local anesthetics include lidocaine, lidocaine hydrochloride, dibucaine, dibucaine hydrochloride, etc. Examples of vasoconstrictors include naphazoline, tetrahydrozoline, methylephedrine or its salts, etc. Examples of the keratoplastic agents include urea, sulfur, salicylic acid or its pharmaceutically acceptable derivatives and salts thereof, nicotinamide, kaolin, bentonite and the like. Among these active ingredients, preferably, as a pimple-preventing cosmetic having an excellent antibacterial and bactericidal effect against acne bacteria and not inhibiting the growth of Staphylococcus epidermidis, there can be mentioned a pimple-preventing facial wash composition containing the component (A): panthenol, isopropylmethylphenol and dipotassium glycyrrhizinate, and a pimple-preventing emulsion.

[0041] As vitamins other than component (A), there are vitamin A compounds [retinol and its pharmaceutically acceptable derivatives and their salts (e.g., retinol palmitate, retinol acetate, retinol, retinal, retinoic acid, retinoids, etc.)], vitamin B6 compounds [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 (e.g., ascorbic acid, sodium ascorbate, magnesium ascorbyl phosphate, sodium ascorbyl palmitate phosphate, erythorbic acid, ascorbic acid 2 - glucoside, ascorbyl palmitate, etc.)], vitamin E [tocopherol and its pharmaceutically acceptable derivatives and their salts (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 B1 [thiamine and its pharmaceutically acceptable derivatives and their salts (e.g., thiamine hydrochloride, thiamine nitrate, etc.)], vitamin B2 [riboflavin and its pharmaceutically acceptable derivatives and their salts (e.g., riboflavin phosphate, sodium riboflavin phosphate, riboflavin butyrate, and sodium flavin adenine dinucleotide, etc.)], vitamin B3 [nicotinic acid and its pharmaceutically acceptable derivatives and their salts (nicotinamide, benzyl nicotinate, etc.)], vitamin B 12Classes [cobalamins and their derivatives and their pharmaceutically acceptable derivatives and salts thereof (e.g., cyanocobalamin, mecobalamin, and hydroxocobalamin hydrochloride, etc.)], biotin, folic acid and its pharmaceutically acceptable derivatives 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 its pharmaceutically acceptable derivatives and salts thereof), etc. can be mentioned.

[0042] (B) As nonionic surfactants other than the component, for example, glycerin fatty acid esters such as glyceryl monostearate and glyceryl monooleate; sorbitan fatty acid esters with an HLB of less than 8 such as sorbitan monostearate, sorbitan monooleate, and sorbitan sesquioleate, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), and polyoxyethylene (20) sorbitan monooleate (polysorbate 80); polyoxyethylene castor oil such as polyoxyethylene (60) castor oil; polyoxyethylene hydrogenated castor oil such as polyoxyethylene hydrogenated castor oil (10) and polyoxyethylene hydrogenated castor oil (60), etc. can be mentioned. As ionic surfactants other than the component (C), examples include N-coconut oil fatty acyl-DL-alanine triethanolamine solution, etc. As ionic surfactants, examples include N-coconut oil fatty acyl-DL-alanine triethanolamine solution, etc.

[0043] Among the nonionic surfactants other than component (B), in the present invention, from the viewpoint of further improving the oil-water separation stability and appearance, it is preferable to further contain one or more glycerin fatty acid esters selected from glyceryl monostearate and glyceryl monooleate with an HLB of 2.5 to 6. When blending the glycerin fatty acid ester with an HLB of 2.5 to 6, the amount is preferably 0.5 to 2% by mass in the topical skin composition.

[0044] When blending a surfactant other than component (B), component (C), and the above glycerin fatty acid ester, the amount is preferably 0.01 to 5% by mass, more preferably 0.01 to 1% by mass in the topical skin composition.

[0045] Examples of the cooling agent include, for example, l-menthol, camphor, borneol or their analogs, eucalyptus oil, peppermint oil, mint oil, etc.

[0046] Examples of the humectant include, for example, polyhydric alcohols (glycerin, 1,3-butylene glycol, 1,2-pentanediol, etc.), sugar alcohols (sorbitol, etc.), hyaluronic acid or its derivatives, heparin analogs, high molecular 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.).

[0047] Examples of the amino acid include glutamic acid, aspartic acid, glycine, alanine, serine, aminoethylsulfonic acid (taurine), and their pharmaceutically acceptable salts (for example, ephedrine hydrochloride, methylphenolin hydrochloride, etc.).

[0048] In addition, higher fatty acids such as stearic acid, isostearic acid, myristic acid, palmitic acid, oleic acid, etc. and behenic acid, etc.; higher fatty alcohols such as cetyl alcohol, stearyl alcohol and behenyl alcohol, etc.; polyhydric alcohols such as propylene glycol and polyethylene glycol, etc.; organic solvents such as acetone, methyl ethyl ketone and ethyl acetate, etc.; pH adjusters such as diisopropanolamine, triethanolamine, lauric acid diethanolamide, sodium hydroxide, hydrochloric acid, citric acid, sodium citrate, potassium dihydrogen phosphate and sodium hydrogen phosphate, etc.; chelating agents such as disodium edetate, ethylenediaminetetraacetate, edetate, pyrophosphate, hexametaphosphate, citric acid, tartaric acid, gluconic acid, etc.; stabilizers such as sodium chloride, sodium thiosulfate and sodium sulfite, etc.; preservatives such as parabens (methylparaben, ethylparaben, butylparaben), boric acid, borax, etc.; cellulose derivatives such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, carmellose, crosscarmellose, ethyl cellulose, methyl cellulose, etc., modified starches such as partially pregelatinized starch, etc., polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, crospovidone, polyethylene glycol, xanthan gum, carrageenan, sodium alginate, gum arabic, guar gum, tamarind gum, karaya gum, carob gum, tragacanth gum, locust bean gum, pullulan, gelatin, carboxyvinyl polymer, acrylic acid / methacrylic acid alkyl copolymer, sodium polyacrylate, hydroxyethyl acrylate / acryloyl dimethyl taurate crosslinked polymer, quince seed (quince), casein, dextrin, sodium pectate, dimethylacrylamide / acryloyl dimethyl taurate crosslinked polymer, dialkyldimethylammonium sulfate cellulose, bentonite, hectorite, magnesium aluminosilicate, laponite, silica anhydride, etc. thickeners, compounded fragrances such as citrus fragrance, floral fragrance, rose fragrance, etc., essential oils (natural fragrances) such as peppermint oil, eucalyptus oil, bergamot oil, rose oil, rosemary oil, lavender oil, lemon oil, etc., pearlescent agents such as ethylene glycol distearate, etc.

[0049] The skin-external composition of the present invention is not particularly limited. For example, it can be obtained by mixing a small aqueous phase containing the above component (A), component (C), optional water-soluble components, and purified water, and a small oil phase containing component (B), component (D), and optional oil-soluble components, and then mixing these small phases.

Examples

[0050] Hereinafter, examples and comparative examples will be shown to specifically explain the present invention, but the present invention is not limited to the following examples. In the following examples, unless otherwise specified, “%” of the composition indicates mass %, and the ratio indicates mass ratio.

[0051] [Examples, Comparative Examples] A small aqueous phase obtained by mixing component (A) and component (C) shown in the table was heated to 80°C. Separately, a small oil phase obtained by mixing component (B) and component (D) shown in the table was heated to 80°C. The small oil phase was added to the small aqueous phase, and emulsification was performed with a desktop homogenizer to prepare a skin-external composition (semi-solid preparation) that is an O / W type emulsion. The pH of the prepared skin-external composition was 7 to 8. For the obtained composition, antibacterial activity evaluation, skin irritation evaluation, and skin moisturizing ability evaluation were performed. Further, 15 g of the obtained composition was filled into a plastic vial container (capacity 20 mL), covered and sealed, and then stored at 50°C for 1 month to evaluate the oil-water separation stability. Also, for Examples 1 and 19, they were further stored at 50°C for 1 month (total storage for 2 months) to evaluate the oil-water separation stability.

[0052] [Antibacterial Activity Evaluation Method] Minimum Inhibitory Concentration (MIC) Evaluation Using Staphylococcus epidermidis isolate (epidermal staphylococcus) and Cutibacterium acnes isolate (acne bacterium), the selective antibacterial effect was evaluated by colony count using the microdilution method. Both of these two strains were obtained from the National Institute of Technology and Evaluation (NBRC), an independent administrative institution. (1) Bacterial Solution Preparation The following bacterial strains were each scraped off with a platinum loop, and Staphylococcus epidermidis was inoculated into SCD liquid medium (Shioya MS Co., Ltd.), and Klebsiella acnes was inoculated into GAM liquid medium (Nissui Pharmaceutical Co., Ltd.). Staphylococcus epidermidis was pre-cultured under aerobic conditions at 37°C for 24 hours, and Klebsiella acnes for 48 hours. The pre-cultured bacterial solutions were each inoculated at 2 x 10 5 To obtain CFU / mL, a bacterial solution was prepared in 2× SCD liquid medium for Staphylococcus epidermidis and in 2× modified GAM bouillon liquid medium (Nissui Pharmaceutical Co., Ltd.) for Klebsiella acnes. Staphylococcus epidermidis: Staphylococcus epidermidis NBRC 12993 Acne bacteria: Cutibacterium acnes NBRC 107605 (2) Test solution Compositions obtained in the examples (3) Test method 100 μL of the test solution was added to a 96-well round-bottom microplate, serially diluted with purified water in a 2-fold dilution series, and 100 μL of the bacterial solution prepared in (1) was inoculated thereto (final bacterial concentration 1 × 10 5 CFU / mL). Staphylococcus epidermidis was then cultured at 32.5℃ under aerobic conditions, and Klebsiella acnes was cultured at 37℃ under anaerobic conditions. 400μL of SCDLP medium was added after 24 hours for Staphylococcus epidermidis and 48 hours for Klebsiella acnes. The bacterial solution was diluted to the specified concentration and spread on GAM agar medium for culture. (4) Judgment criteria <Criteria for determining antibacterial activity> The difference (ΔLOG) between the number of bacteria cultured by adding water instead of the test liquid (LOG control) and the number of bacteria cultured by reacting with the test liquid (LOG sample) was evaluated. Tables 1 to 4 show the dilution ratio of the test liquid. If growth was positive without dilution, "-" is entered. Criteria for negative growth (antibacterial): ΔLOG>2 Criteria for positive growth: ΔLOG≦2 <Criteria for determining selective antibacterial activity> ○: Propionibacterium acnes was antibacterial with a sample diluted 8 times or more (growth negative), and Staphylococcus epidermidis was not antibacterial without dilution (growth positive) △: The acne bacteria are antibacterial up to the 4-fold diluted sample (negative growth), and the Staphylococcus epidermidis is not antibacterial without dilution (positive growth). ×: The acne bacteria are antibacterial or not antibacterial up to the 2-fold diluted sample. Or the Staphylococcus epidermidis is antibacterial without dilution (negative growth).

[0053] [Oil-water separation stability] The composition stored at 50°C for 1 month was taken out of the storage, and the appearance immediately after taking out was observed and evaluated according to the following evaluation criteria. [Evaluation criteria] ◎: The emulsified state is uniform and no separation is observed. ○: There is a tendency to cream, but no separation is observed. △: Slight separation of the aqueous layer and the oil layer is observed. ×: Clear separation of the aqueous layer and the oil layer is observed.

[0054] [Skin irritation] Five expert panelists evaluated the skin irritation (tingling sensation, burning sensation) when each composition (about 0.75 g) was spread on the skin according to the following 4-level scoring system. [Scoring criteria] 4: No irritation is felt. 3: A slight irritation is felt. 2: Irritation is felt. 1: A strong irritation is felt. The scores were averaged and the second decimal place was rounded off, and the skin irritation was evaluated according to the following evaluation criteria. [Evaluation criteria] ◎: The average score is 3.5 or more. ○: The average score is 3 or more and less than 3.5. △: The average score is 2 or more and less than 3. ×: The average score is less than 2.

[0055] [Skin moisturizing power (moisturizing feeling)] Five expert panelists evaluated the skin moisturizing power 4 hours after applying each composition (about 0.75 g) to the skin according to the following 4-level scoring system. [Scoring criteria] 4: A moist feeling is felt. 3: Slightly feel a moist feeling 2: The moist feeling is insufficient and a dry feeling is felt 1: The moist feeling cannot be felt and a strong dry feeling is felt The scores were averaged, rounded to the second decimal place, and the skin moisturizing power was evaluated according to the following evaluation criteria. <Evaluation Criteria> ◎: The average score is 3.5 or more ○: The average score is 3 or more and less than 3.5 △: The average score is 2 or more and less than 3 ×: The average score is less than 2

[0056]

Table 1

[0057]

Table 2

[0058]

Table 3

[0059]

Table 4

[0060] As shown in Tables 1 to 4, the skin-external use compositions of Examples 1 to 19 had excellent antibacterial and bactericidal effects against acne bacteria and had selective antibacterial properties that did not inhibit the growth of Staphylococcus epidermidis. Also, as a result of storage at 50°C for 2 months, Example 1 was "○: There is a tendency to cream, but no separation is observed", and Example 19 was "◎: The emulsified state is uniform and no separation is observed". Also, the appearance of Example 19 was in a state where the appearance of the preparation was very smooth and shiny compared to Example 1.

[0061] The raw materials used in preparing the examples and comparative examples are shown below. The descriptions of "JP Pharmacopoeia", "Non-JP Pharmacopoeia", "Pharmaceutical Additive Standard", and "External Raw Material Standard" below respectively mean that the raw materials comply with the 18th Revised Japanese Pharmacopoeia Standard, Japanese Pharmacopoeia Non-pharmaceutical Drug Standard, Pharmaceutical Additive Standard (2018), and External Raw Material Standard for Quasi-drugs (2021). Panthenol:: External Raw Material Standard, D-pantothenyl alcohol, manufactured by DSM Co., Ltd. Polyethylene glycol monolaurate (10 EO): (HLB 12.5), External Raw Material Standard, NIKKOL MYL-10, manufactured by Nikko Chemicals Co., Ltd. Polyoxyethylene sorbitan monolaurate (6 EO): (HLB 15.5), External Raw Material Standard, NIKKOL GL-1, manufactured by Nikko Chemicals Co., Ltd. Polyoxyethylene glyceryl monolaurate (9 EO): (HLB 12.0), EMALEX GWL-109, manufactured by Nippon Emulsion Co., Ltd. Polyoxyethylene lauryl ether (10): (HLB 12.0), External Raw Material Standard, EMALEX 710, manufactured by Nippon Emulsion Co., Ltd. Polyoxyethylene lauryl ether (15): (HLB 14.0), External Raw Material Standard, EMALEX 715, manufactured by Nippon Emulsion Co., Ltd. Polyoxyethylene lauryl ether (20): (HLB 15.0), External Raw Material Standard, EMALEX 720, manufactured by Nippon Emulsion Co., Ltd. Sodium stearoyl methyl taurate: External Raw Material Standard, NIKKOL SMT, manufactured by Nikko Chemicals Co., Ltd. Sodium N-stearoyl-L-glutamate: External Raw Material Standard, Eumulgin SG, manufactured by BASF Japan Ltd. Sodium stearoyl lactate: External Raw Material Standard, sodium stearoyl lactate, manufactured by Nikko Chemicals Co., Ltd. Liquid isoparaffin: External Raw Material Standard, Pearl Rim 6, manufactured by NOF Corporation Glyceryl tri(2-ethylhexanoate): External Raw Material Standard, NIKKOL TRIFAT S-308, manufactured by Nikko Chemicals Co., Ltd. Methylpolysiloxane: External Raw Material Standard, DOWSIL SH200C FLUID 20CS, manufactured by Dow Corning Toray Co., Ltd. Glyceryl monostearate: (HLB 4.0), external standard, MGS-ASEV, manufactured by Nikko Chemicals Co., Ltd.

Claims

1. (A) One or more selected from pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol, and pantothenyl ethyl ether, (B) One or more selected from polyethylene glycol fatty acid esters, polyoxyethylene sorbit fatty acid esters, sorbitan fatty acid esters, polyglycerin fatty acid esters, and polyoxyethylene glycerin fatty acid esters, in which the fatty acid chain length is 12 to 18, and polyoxyethylene alkyl ethers with an alkyl chain length of 12 to 18, and having an HLB of 8 to 16, and (C) One or more selected from N-myristoyl-L-glutamate, N-stearoyl-L-glutamate, myristoyl methyl taurine salt, N-stearoyl-N-methyl taurine salt, and stearoyl lactate, A skin external composition that is an O / W type emulsion and contains the above.

2. The skin external composition according to claim 1, wherein the component (B) is one or more selected from polyethylene glycol fatty acid esters, polyoxyethylene sorbit fatty acid esters, sorbitan fatty acid esters, and polyoxyethylene glycerin fatty acid esters, in which the fatty acid chain length is 12 to 14, and polyoxyethylene alkyl ethers with an alkyl chain length of 12 to 14.

3. The skin external composition according to claim 1, wherein the content of the component (C) is 0.01 to 3% by mass.

4. The skin external composition according to claim 1, further containing (D) one or more selected from ester oils, hydrocarbon oils, and silicone oils.

5. The skin external composition according to claim 4, wherein the mass ratio (C) / (D) of the component (C) to the component (D) is 0.0008 to 0.

35.

6. The skin external composition according to claim 4, wherein the mass ratio [(A)+(B)] / (D) of the total of the component (A) and the component (B) to the component (D) is 0.025 to 0.

6.

7. The skin external composition according to any one of claims 1 to 6, which is for acne treatment or prevention.

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