Agents for maintaining the growth state of skin resident bacteria, agents for suppressing skin inflammation caused by skin resident bacteria, and cosmetics, pharmaceuticals, or quasi-drugs using these agents, as well as methods for maintaining the growth state of skin resident bacteria and methods for suppressing skin inflammation caused by skin resident bacteria.

Abstract

To provide a novel technique that maintains the growth state of skin resident bacteria, and suppresses the occurrence of skin trouble.SOLUTION: An agent for maintaining growth state of skin resident bacteria comprises Isodon japonicus extract as an active ingredient. The present technique also provides an agent for suppressing skin inflammation by skin resident bacteria that comprises Isodon japonicus extract as an active ingredient. The agent according to the present technique can maintain the growth state of skin resident bacteria and can suppress skin inflammation by skin resident bacteria. The agent according to the present technique can be used as pharmaceuticals, topical skin preparations, quasi drugs and cosmetics.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present technology relates to an agent for maintaining the growth state of skin commensal bacteria. More specifically, it relates to an agent for maintaining the growth state of skin commensal bacteria, an agent for suppressing skin inflammation caused by skin commensal bacteria, a cosmetic, a pharmaceutical or a quasi-drug using these agents, a method for maintaining the growth state of skin commensal bacteria, and a method for suppressing skin inflammation caused by skin commensal bacteria. Background Art

[0002] Commensal bacteria are important for maintaining health, and the term "gut flora" has come into general use. However, many commensal bacteria also exist on the skin, which is said to be the largest organ of the human body, and they play various roles in maintaining skin health.

[0003] For example, Staphylococcus epidermidis produces fatty acids and glycerol. The fatty acids maintain the skin in a weakly acidic state and induce the production of antimicrobial peptides, thereby preventing the proliferation of highly pathogenic Staphylococcus aureus, while glycerol plays a role in maintaining the skin barrier function.

[0004] Furthermore, for example, Cutibacterium acnes produces propionic acid and fatty acids to maintain a weakly acidic skin surface, and plays a role in suppressing the proliferation of highly pathogenic bacteria adhering to the skin. Although Cutibacterium acnes is said to be a cause of acne, it is known that it does not become an acne-causing bacterium unless it proliferates excessively.

[0005] Furthermore, technologies for improving or maintaining good skin condition by utilizing commensal bacteria present on the skin have also been developed. For example, Patent Document 1 discloses a technology that promotes the production of glycerol derived from Staphylococcus epidermidis by using dead cells of Enterococcus lactic acid bacteria. In addition, Patent Document 2 discloses a technology that promotes hyaluronic acid production by using dead cells of lactic acid bacteria belonging to the genus Enterococcus. Prior Art Documents Patent Documents

[0006] [Patent Document 1] Japanese Patent Publication No. 2017-101006 [Patent Document 2] Japanese Patent Publication No. 2020-105100 [Overview of the Initiative] [Problems that the invention aims to solve]

[0007] It is said that each person has dozens of different types of commensal bacteria on their skin, and these differ from person to person, making the range of commensal bacteria that can exist on human skin extremely diverse. When the balance of these commensal bacteria is disrupted, it can cause skin problems such as inflammation. Therefore, maintaining a balance of commensal bacteria on the skin is extremely important in order to prevent skin problems.

[0008] Therefore, the primary objective of this technology is to provide a novel technique for maintaining the growth state of commensal bacteria present on the skin and suppressing the occurrence of skin problems. [Means for solving the problem]

[0009] The inventors of this invention diligently searched for a substance that maintains the balance of commensal bacteria present on the skin and suppresses the occurrence of skin problems. They discovered that an extract of Isodon japonicus can suppress skin inflammation caused by these commensal bacteria while maintaining the growth state of the commensal bacteria present on the skin, thus completing the present invention. To suppress skin inflammation caused by bacteria, it is common to use antibacterial components to kill bacteria or suppress bacterial growth, but this technology is able to suppress skin inflammation caused by commensal bacteria while maintaining the growth state of the skin's commensal bacteria.

[0010] In other words, this technology first provides an agent that maintains the growth state of skin resident bacteria, with an extract of Isodon japonicus as the active ingredient. This technology also provides an agent that suppresses skin inflammation caused by skin commensal bacteria, with an extract of Isodon japonicus as the active ingredient. The agent related to this technology can maintain the growth state of skin resident bacteria and suppress skin inflammation caused by skin resident bacteria. The agent related to this technology can maintain the growth state of Enterococcus bacteria. The agent related to this technology can suppress skin inflammation caused by Enterococcus bacteria. The agent related to this technology can suppress the production of TNF-α. As the Isodon japonicus extract used in the agent relating to this technology, an aqueous alcohol extract can be used. In this case, the Isodon japonicus extract can be an aqueous alcohol extract with an alcohol concentration of 30-70% (V / V).

[0011] The agent relating to this technology can be used in cosmetics, pharmaceuticals, or quasi-drugs. The content of the Isodon japonicus extract in cosmetics, pharmaceuticals, or quasi-drugs may be set to 0.00001% by mass or more on a dry solids basis.

[0012] This technology then provides a method for maintaining the growth of skin resident bacteria and a method for suppressing skin inflammation caused by skin resident bacteria, which includes the step of applying an extract of Isodon japonicus to the skin. [Effects of the Invention]

[0013] This technology makes it possible to suppress skin inflammation caused by commensal bacteria while maintaining the growth state of commensal bacteria present on the skin. However, the effects of this technology are not limited to those described herein, and may include any of the effects described in this specification. [Brief explanation of the drawing]

[0014] [Figure 1] It is a graph showing the relative expression ratio of the TNF-α gene in Experimental Example 1. MODE FOR CARRYING OUT THE INVENTION

[0015] Hereinafter, preferred embodiments for carrying out the present technology will be described. The embodiments described below show representative embodiments of the present technology, and the scope of the present technology is not limited only to these embodiments.

[0016] 1. Agent The agent according to the present technology comprises an extract of Isodon japonicus as an active ingredient. The agent according to the present technology has an effect of maintaining the growth state of skin resident bacteria. Further, the agent according to the present technology has an effect of suppressing skin inflammation caused by skin resident bacteria. That is, the agent according to the present technology is an agent capable of suppressing skin inflammation caused by skin resident bacteria while maintaining the growth state of skin resident bacteria, without killing bacteria or suppressing the proliferation of bacteria.

[0017] The type of said skin resident bacteria is not particularly limited, and examples thereof include bacteria of the genus *Enterococcus*, bacteria of the genus *Staphylococcus*, bacteria of the genus *Corynebacterium*, bacteria of the genus *Bacillus*, bacteria of the genus *Cutibacterium*, and the like. Among these, the agent according to the present technology can particularly suppress skin inflammation caused by bacteria of the genus *Enterococcus* while maintaining the growth state of bacteria of the genus *Enterococcus*.

[0018] The agent according to the present technology can suppress the production of TNF-α (Tumor Necrosis Factor-α). TNF-α is an inflammatory cytokine produced during inflammation by macrophages, lymphocytes, fibroblasts, keratinocytes and the like.

[0019] Hereinafter, the details of the ingredients used in the agent according to the present technology will be described.

[0020] (1) Extract of Isodon japonicus Isodon japonicus is a perennial plant belonging to the genus Isodon of the family Lamiaceae, also known by the alternative name Hikiokoshi, and its scientific name is Isodon japonicus. The Isodon japonicus extract refers to an extract obtained by extracting the roots, stems, leaves, flowers, fruits and the like of Isodon japonicus with a suitable solvent, and usually a concentrated solution of the extracted solvent is used. Further, a product obtained by freeze-drying the concentrated solution can also be used in the present technology.

[0021] The specific extraction site of Isodon japonicus is not particularly limited as long as the object of the present technology is not impaired, but it is preferable to select an aerial part, and it is more preferable to select leaves and / or stems. Further, the extraction site may be used for extraction immediately after collection, or may be used for extraction after drying. If necessary, processing such as crushing, cutting, shredding, and shaping can be performed before extraction.

[0022] The solvent used for extraction is also not particularly limited, and usually one or two or more types of solvents that can be used for plant extraction can be freely selected and used. Examples thereof include water, alcohols, glycols, ketones, esters, ethers, halogenated carbons, supercritical solvents (such as carbon dioxide), and subcritical solvents. Examples of alcohols include ethanol, methanol, and propanol. Examples of glycols include ethylene glycol, diethylene glycol, butylene glycol, propylene glycol, and dipropylene glycol. Examples of ketones include acetone and methyl ethyl ketone. Examples of esters include ethyl acetate, propyl acetate, and ethyl formate. These solvents may be used alone or as an aqueous solution, or may be used as a mixed solvent of any two or three or more types. In the present technology, among these, it is particularly preferable to use hydrous alcohol.

[0023] In this technology, when aqueous alcohol is used as the extraction solvent, its concentration is not particularly limited, but it is preferable to use aqueous alcohol with an alcohol concentration of 30-70% (V / V).

[0024] The extraction method is not particularly limited, and any extraction method commonly used in plant extraction can be freely selected and used. For example, one method is to immerse any part of the Enmeisou plant in the solvent for 24 hours and then filter it, or to extract the material while heating and stirring at a temperature below the boiling point of the solvent and then filter it.

[0025] The extract of Enmeisou can be used as is as the active ingredient in the agent relating to this technology, but it is also possible to further fractionate the highly active fraction from the extract using appropriate separation methods (for example, partition extraction, gel filtration, silica gel chromatography, reverse-phase or normal-phase high-performance liquid chromatography, etc.) before use.

[0026] The dry solid content concentration of the Enmeisou extract used in the agent according to this technology can be freely set according to the type of extraction solvent used, the extraction method, etc., as long as the effects of this technology are not impaired. In particular, the lower limit of the dry solid content concentration can be, for example, 0.00001% by mass or more, preferably 0.00005% by mass or more, more preferably 0.0001% by mass or more, and even more preferably 0.0005% by mass or more. By increasing the dry solid content concentration of the Enmeisou extract used in the agent according to this technology, the effect of maintaining the growth state of skin commensal bacteria and / or the effect of suppressing skin inflammation caused by skin commensal bacteria can be more reliably exerted. Furthermore, the upper limit of the dry solid content concentration can be, for example, 0.1% by mass or less, preferably 0.05% by mass or less, more preferably 0.01% by mass or less, and even more preferably 0.005% by mass or less. By not increasing the dry solid content concentration of the Enmeisou extract used in the agent related to this technology too much, it is possible to prevent the generation of plant-derived odors and precipitates, and to improve the effect of maintaining the growth state of skin resident bacteria.

[0027] (2) Others The agent relating to this technology may also contain, as long as it does not impair the effects of this technology, one or more other ingredients that can be used in the fields of cosmetics, pharmaceuticals, or quasi-drugs, which can be freely selected. For example, ingredients such as preservatives, emulsifiers, pH adjusters, colorants, antiseptics, and surfactants can be used.

[0028] 2. Cosmetics The agent relating to this technology can be suitably used in all forms of cosmetics by utilizing its excellent effect of maintaining the growth state of skin resident bacteria and / or suppressing skin inflammation caused by skin resident bacteria. For example, it can be applied to skincare cosmetics such as lotions, emulsions, creams, serums, and face masks; makeup cosmetics such as foundations, concealers, makeup bases, lipsticks, blushes, eyeshadows, and eyeliners; sunscreens; shampoos, conditioners, and treatments. Examples of cosmetic formulations include water-based, oil-based, soluble, and emulsion types (O / W type, W / O type, W / O / W type, O / W / O type).

[0029] In addition to the agent related to this technology, the cosmetic composition may contain one or more ingredients that can be freely selected and blended with ingredients that can be commonly used in cosmetics. For example, it may contain all additives that can be commonly used in the field of cosmetics, such as base materials, preservatives, emulsifiers, colorants, antiseptics, surfactants, UV absorbers, antioxidants, humectants, fragrances, antifungal agents, extender pigments, colorants, alcohol, and water.

[0030] Furthermore, because the active ingredient of the agent related to this technology is derived from natural ingredients, there is little need to be careful when using it in combination with other active ingredients. Therefore, in addition to the agent related to this technology, other active ingredients can be freely added to the cosmetic composition as needed.

[0031] In the cosmetic composition relating to this technology, the content of the agent relating to this technology is not particularly limited and can be freely set according to the purpose. In this technology, the lower limit of the dry solid content of Enmeisou extract in the cosmetic composition can be, for example, 0.00001% by mass or more, preferably 0.00005% by mass or more, more preferably 0.0001% by mass or more, and even more preferably 0.0005% by mass or more. By increasing the dry solid content of Enmeisou extract in the cosmetic composition relating to this technology, the effect of maintaining the growth state of skin resident bacteria and / or the effect of suppressing skin inflammation caused by skin resident bacteria can be more reliably exerted. Furthermore, the upper limit of the dry solid content of Enmeisou extract in the cosmetic composition can be, for example, 0.1% by mass or less, preferably 0.05% by mass or less, more preferably 0.01% by mass or less, and even more preferably 0.005% by mass or less. By not increasing the dry solid content of Enmeisou extract too much in the cosmetic composition related to this technology, it is possible to prevent the generation of plant-derived odors and precipitates, and to improve the effect of maintaining the growth state of skin resident bacteria.

[0032] Cosmetics using the agent related to this technology, as described above, are highly safe and can be used continuously for extended periods because their active ingredients are derived from natural sources.

[0033] 3. Pharmaceuticals and quasi-drugs The agents relating to this technology can be suitably used in pharmaceuticals and quasi-drugs by utilizing their excellent effect in maintaining the growth state of skin resident bacteria and / or suppressing skin inflammation caused by skin resident bacteria. Pharmaceuticals and quasi-drugs are preferably formulated into the dosage form of topical skin preparations. Examples of topical skin preparations include topical liquids, topical gels, creams, ointments, sprays, liniments, lotions, poultices, plasters, sprays, aerosols, and patches.

[0034] Pharmaceuticals and quasi-drugs relating to this technology may contain one or more pharmacologically acceptable additives, which can be freely selected. For example, when pharmaceuticals and quasi-drugs relating to this technology are applied to topical skin preparations, they may contain all additives that are commonly used in the field of pharmaceutical and quasi-drug formulations, such as bases, surfactants, preservatives, emulsifiers, colorants, deodorizers, fragrances, stabilizers, antiseptics, antioxidants, lubricants, solubilizers, and suspending agents.

[0035] Because the active ingredient of the agent related to this technology is derived from natural ingredients, there is little need to be careful when using it in combination with other drugs. Therefore, it is possible to freely select one or more existing drugs and combine them into a single agent. For example, any drug such as antibacterial agents, anti-inflammatory and analgesic agents, steroids, antifungal agents, antihistamines, and vitamins can be combined. Furthermore, ingredients that have effects on preventing, improving, and / or treating diseases and symptoms that are conventionally known or may be discovered in the future can be used in combination as appropriate, as long as they do not impair the effects of this technology.

[0036] In pharmaceuticals and quasi-drugs relating to this technology, the content of the agent relating to this technology is not particularly limited and can be freely set according to the purpose. In this technology, the lower limit of the dry solid content of Enmeisou extract in pharmaceuticals and quasi-drugs can be, for example, 0.00001% by mass or more, preferably 0.00005% by mass or more, more preferably 0.0001% by mass or more, and even more preferably 0.0005% by mass or more. By increasing the dry solid content of Enmeisou extract in pharmaceuticals and quasi-drugs relating to this technology, the effect of maintaining the growth state of skin resident bacteria and / or the effect of suppressing skin inflammation caused by skin resident bacteria can be more reliably exerted. Furthermore, the upper limit of the dry solid content of Enmeisou extract in pharmaceuticals and quasi-drugs can be, for example, 0.1% by mass or less, preferably 0.05% by mass or less, more preferably 0.01% by mass or less, and even more preferably 0.005% by mass or less. By not excessively increasing the content of dried solids of Enmeisou extract in pharmaceuticals and quasi-drugs related to this technology, it is possible to prevent the generation of plant-derived odors and precipitates, and to improve the effect of maintaining the growth state of skin resident bacteria.

[0037] The pharmaceuticals and quasi-drugs related to this technology, as described above, have naturally derived active ingredients, making them highly likely to be safe for administration to patients suffering from various diseases. Furthermore, the likelihood of side effects is low even with long-term, continuous administration.

[0038] 4. Methods for maintaining the growth of commensal skin bacteria and methods for suppressing skin inflammation caused by commensal skin bacteria. A method for maintaining the growth of skin resident bacteria and a method for suppressing skin inflammation caused by skin resident bacteria include the step of applying an extract of Enmeisou to the skin. The extract of Enmeisou can be applied to the skin in the form of cosmetics, pharmaceuticals, or quasi-drugs containing it, or it can be applied to the skin in its undiluted state or as a diluted solution diluted with any solvent.

[0039] The application method is not particularly limited and can be freely applied depending on the application form of the cosmetic, pharmaceutical, or quasi-drug used. Examples include application with fingers, application with tools such as spatulas or cotton swabs, direct spraying onto the skin, patting with cotton, gauze, or other cloth, and applying cotton, gauze, or other cloth coated with Enmeisou extract to the skin. [Examples]

[0040] The present technology will be described in more detail below based on the following examples. The examples described below are representative examples of the present technology and should not be interpreted as narrowing the scope of the present technology.

[0041] <Preparation of Enmeisou extract> The dried and pulverized above-ground parts of Enmeisou were placed in an extraction solvent, and the components of the above-ground parts were extracted. After removing insoluble matter by filtration, the amount of solids was adjusted with the solvent to obtain Enmeisou extract. 50% aqueous ethanol was used as the extraction solvent. The Enmeisou extract was prepared as a 50% aqueous ethanol aqueous solution containing 1% by mass of dry solids. In Experimental Example 1, a 50% aqueous ethanol extract of Paeonia suffruticosa, which has long been known for its anti-inflammatory effects, was also used as a comparison.

[0042] <Experimental Example 1> Experimental Example 1 investigated the inhibitory effect of Enmeisou extract on inflammation caused by skin commensal bacteria. In this experiment, the expression level of the inflammatory factor TNF-α gene was used as an indicator of inflammation. Enterococcus bacteria were used as an example of skin commensal bacteria.

[0043] (1) Experimental method Human epidermal keratinocytes (NHEK cells (normal human epidermal keratinocytes) from human neonatal foreskin) were seeded in a 6-well plate containing culture medium (HuMedia-KG2 (Kurabo Industries Ltd.)). After 48 hours of incubation, co-culturing with live Enterococcus bacteria was started, and simultaneously, after adjusting the final ethanol concentration to 0.05% by mass, each sample shown in Figure 1 (described later) was added. After 24 hours of incubation, RNA was extracted from the cells using an RNA extraction kit (QIAGEN), and cDNA was synthesized using the iScript Advanced cDNA Synthesis Kit for RT-qPCR (BIO-RAD) with the obtained RNA as a template. The gene expression level was measured using quantitative PCR (polymerase chain reaction) with the synthesized cDNA. SsoAdvanced Universal SYBR Green Supermix (BIO-RAD) was used for quantitative PCR. As an internal standard, the expression level of the housekeeping gene GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) was quantified, and the relative expression ratio to GAPDH was calculated to determine the relative expression ratio of the TNF-α gene.

[0044] (2) Results The relative expression levels of the TNF-α gene are shown in the graph in Figure 1. As shown in Figure 1, when comparing the control and the Enterococcus-added sample, it was found that the coexistence of human epidermal keratinocytes and Enterococcus bacteria significantly increased the inflammatory factor TNF-α. From these results, it was found that Enterococcus bacteria, which are commensal bacteria of the skin, exacerbate skin inflammation.

[0045] When only 50% aqueous ethanol, the sample dilution solvent, was added in the same amount as when the sample was added, no significant difference was observed in TNF-α expression levels. This result confirms that 50% aqueous ethanol does not have an anti-inflammatory effect on the skin.

[0046] In samples treated with 0.01% by mass and 0.1% by mass of Enmeisou extract, TNF-α expression was significantly reduced compared to the sample treated with only the solvent (50% aqueous ethanol). On the other hand, the TNF-α expression level in the sample treated with peony root extract, which has long been known for its anti-inflammatory effects, was equivalent to or higher than that of the sample treated with only the solvent (50% aqueous ethanol). These results confirm that Enmeisou extract has an anti-inflammatory effect on the skin, but peony root extract does not.

[0047] <Experimental Example 2> In Experiment Example 2, the effect of Enmeisou extract on maintaining the growth state of skin commensal bacteria was investigated. In this experiment, Enterococcus, Staphylococcus, Corynebacterium, and Bacillus bacteria were used as skin commensal bacteria.

[0048] (1) Experimental method Add the Enmeisou extract to the liquid culture medium at concentrations of 0%, 0.001%, 0.01%, 0.1%, 1%, and 10% by mass, and then add 10 5~6 Each bacterium was mixed to a concentration of CFU / mL, incubated at 32.5°C for 24 hours, and the bacterial count was measured by pour plate. Compared to the bacterial count of 0% by mass of Enmeisou extract (no sample added), samples with a bacterial count of less than ±0.5 Log were marked with ◎, samples with a bacterial count difference of 0.5 Log or more but less than 2 Log were marked with ○, samples with a bacterial count difference of 2 Log or more but less than 5 Log were marked with △, and samples where the bacteria were dead were marked with ×.

[0049] (2) Results Table 1 shows the results of measuring the bacterial count for each type of bacteria.

[0050] [Table 1]

[0051] As shown in Table 1, the Enmeisou extract had almost no effect on the bacterial count compared to the sample without the extract added, indicating that it does not affect the commensal skin flora. From these results, it was confirmed that the Enmeisou extract has an effect on maintaining the growth state of commensal skin flora.

[0052] Furthermore, the results from Experimental Examples 1 and 2 showed that Enmeisou extract suppresses inflammation caused by skin resident bacteria while also maintaining the growth state of these bacteria. In other words, Enmeisou extract can suppress inflammation while preserving the balance of the skin microbiota. Although the mechanism by which Enmeisou extract suppresses inflammation caused by skin resident bacteria is not clear, it is presumed that the mechanism of action does not involve killing skin resident bacteria or inhibiting their growth to suppress inflammation.

[0053] <Examples 1-6> In Examples 1-6, pharmaceuticals, quasi-drugs, and cosmetics containing Enmeisou extract were prepared. In addition to the 50% aqueous ethanol extract, the Enmeisou extract used was prepared according to the conditions in <Preparation of Enmeisou Extract> above, but with the extraction solvent changed to 30% aqueous ethanol, 70% aqueous ethanol, 50% aqueous 1,3-butylene glycol, and 100% water.

[0054] [Example 1: Topical Solution] The topical solution was prepared using the following method. (Manufacturing method) A. The following components (1) to (7) were mixed and dissolved. B. The following components (8) to (11) were mixed and dissolved. CA was mixed with B to obtain the topical solution according to Example 1.

[0055] (1) Citric acid: 0.05% by mass (2) Sodium citrate: 0.2% by mass (3) Sodium pyrrolidone carboxylate (50%) solution: 0.5% by mass (4) Glycerin: 3.0% by mass (5) 1,3-Butylene glycol: 8.0% by mass (6) Enmeisou 50% aqueous ethanol extract: 0.5% by mass (7) Purified water: remaining amount (8) Ethanol: 10.0% by mass (9) Fragrance: 0.05% by mass (10) Methylparaben: 0.1% by mass (11) Polyoxyethylene (20E.O.) sorbitan monooleate: 0.5% by mass

[0056] [Example 2: Emulsion] The emulsion was prepared using the following method. (Manufacturing method) A. The following components (1) to (10) were heated and dissolved, and the temperature was maintained at 70°C. B. The following components (11) to (17) were heated and dissolved, and the temperature was maintained at 70°C. CA was emulsified with B, and then the following ingredient (18) was added and mixed. The DC was cooled, and the following component (19) was added and mixed to obtain the emulsion according to Example 2.

[0057] (1) Stearic acid: 1.0% by mass (2) Cetanol: 0.5% by mass (3) Lipophilic glyceryl monostearate: 0.5% by mass (4) Liquid paraffin: 2.0% by mass (5) Squalane: 3.0% by mass (6) Jojoba oil: 3.0% by mass (7) Cetyl palmitate: 0.2% by mass (8) Methylparaben: 0.15% by mass (9) Sorbitan monostearate: 0.3% by mass (10) Polyoxyethylene (20E.O.) sorbitan monooleate: 0.5% by mass (11) Triethanolamine: 0.5% by mass (12) 1,3-Butylene glycol: 15.0% by mass (13) Glycerin: 3.0% by mass (14) Polyethylene glycol 6000: 0.5% by mass (15) Enmeisou 30% aqueous ethanol extract: 0.1% by mass (16) Magnesium ascorbate phosphate: 0.5% by mass (17) Purified water: remaining amount (18) 1% carboxyl vinyl polymer solution: 8.0% by mass (19) Fragrance: 0.1% by mass

[0058] [Example 3: Ointment] The ointment was prepared using the following method. (Manufacturing method) A. The following components (1) to (13) were heated and dissolved, and the temperature was maintained at 70°C. B. The following components (14) to (19) were heated and dissolved, and the temperature was maintained at 70°C. CA was emulsified with B, and then the following ingredient (20) was added and mixed. The DC was cooled, and the following component (21) was added and mixed to obtain the ointment according to Example 3.

[0059] (1) Stearic acid: 2.5% by mass (2) Cetanol: 2.5% by mass (3) Lipophilic glyceryl monostearate: 2.0% by mass (4) Petrolatum: 2.0% by mass (5) Dipentaerythritol fatty acid ester: 2.0% by mass (6) Isotridecyl myristate: 5.0% by mass (7) Liquid paraffin: 8.0% by mass (8) Squalane: 5.0% by mass (9) Beeswax: 1.0% by mass (10) Cetyl palmitate: 2.0% by mass (11) Sorbitan sesquioleate: 0.5% by mass (12) Polyoxyethylene (20E.O.) sorbitan monooleate: 1.5% by mass (13) Phenoxyethanol: 0.3% by mass (14) Triethanolamine: 1.2% by mass (15) 1,3-Butylene glycol: 8.0% by mass (16) Glycerin: 2.0% by mass (17) Polyethylene glycol 20000: 0.5% by mass (18) Enmeisou 70% aqueous ethanol extract: 1.0% by mass (19) Purified water: remaining amount (20) 1% carboxyl vinyl polymer solution: 10.0% by mass (21) Fragrance: 0.3% by mass

[0060] [Example 4: Serum] The serum was prepared using the following method. (Manufacturing method) A. The following components (1) to (8) were mixed and dissolved. B. The following components (9) to (18) were mixed and dissolved. A was added to CB and mixed to obtain the beauty serum according to Example 4.

[0061] (1) Glyceryl tri-2-ethylhexanoate: 0.1% by mass (2) Meadowhome oil: 0.05% by mass (3) Jojoba oil: 0.05% by mass (4) Phenoxyethanol: 0.2% by mass (5) Fragrance: 0.2% by mass (6) Polyoxyethylene (20E.O.) sorbitan monooleate: 0.5% by mass (7) Polyoxyethylene hydrogenated castor oil isostearate (50 E.O.): 1.5% by mass (8) Ethanol: 5.0% by mass (9) Glycerin: 4.0% by mass (10) Dipropylene glycol: 8.0% by mass (11) 1,3-Butylene glycol: 8.0% by mass (12) Sodium lactate: 0.5% by mass (13) Sodium pyrrolidone carboxylate (50%) solution: 0.5% by mass (14) Enmeisou 50% hydrated 1,3-butylene glycol extract: 10.0% by mass (15) Arbutin: 0.2% by mass (16) Hydroxyethylcellulose: 0.08% by mass (17) Sodium alginate: 0.05% by mass (18) Purified water: remaining amount

[0062] [Example 5: Pack] The packs were prepared using the following method. (Manufacturing method) A. The following components (1) to (6) were heated and dissolved. B. The following components (7) to (11) were mixed and dissolved. After cooling CA, B was added and mixed to obtain the pack according to Example 5.

[0063] (1) Polyvinyl alcohol: 12.0% by mass (2) Methylcellulose: 0.1% by mass (3) Glycerin: 3.0% by mass (4) 1,3-Butylene glycol: 5.0% by mass (5) Water extract of Enmeisou: 5.0% by mass (6) Purified water: remaining amount (7) Fragrance: 0.05% by mass (8) Methylparaben: 0.05% by mass (9) Glyceryl tri-2-ethylhexanoate: 0.1% by mass (10) Polyoxyethylene (20E.O.) sorbitan monooleate: 1.0% by mass (11) Ethanol: 13.0% by mass

[0064] [Example 6: Liquid Foundation (O / W type)] The liquid foundation was prepared using the following method. (Manufacturing method) A. The following components (1) to (7) were heated and dissolved. The following ingredients (8) to (11) were added to BA, mixed uniformly, and kept at 70°C. C. The following components (12) to (16) were heated and dissolved, and the temperature was maintained at 70°C. Add B to DC and emulsify. After cooling the ED, the following component (17) was added and mixed to obtain the liquid foundation (O / W type) according to Example 6.

[0065] (1) Stearic acid: 2.0% by mass (2) Cetanol: 0.5% by mass (3) Behenyl alcohol: 1.0% by mass (4) Vaseline: 2.5% by mass (5) Liquid paraffin: 5.0% by mass (6) Self-emulsifying glyceryl monostearate: 1.0% by mass (7) Phenoxyethanol: 0.25% by mass (8) Titanium oxide: 6.0% by mass (9) Colored pigment: 4.0% by mass (10) Mica: 2.0% by mass (11) Talc: 4.0% by mass (12) Carboxymethylcellulose: 0.2% by mass (13) Bentonite: 0.4% by mass (14) Enmeisou 50% aqueous ethanol extract: 0.01% by mass (15) 1,3-Butylene glycol: 8.0% by mass (16) Purified water: remaining amount (17) Fragrance: 0.3% by mass

Claims

1. An anti-inflammatory agent for skin inflammation caused by Enterococcus bacteria, containing an extract of Isodon japonicus as the active ingredient.

2. An Enterococcus bacterium-induced skin inflammation inhibitor according to claim 1, which suppresses the production of TNF-α.

3. The Enterococcus bacterium-induced skin inflammation inhibitor according to claim 1 or 2, wherein the extract of Isodon japonicus is an aqueous alcohol extract.

4. The Enterococcus bacterium-induced skin inflammation inhibitor according to claim 3, wherein the extract of Isodon japonicus is an aqueous alcohol extract with an alcohol concentration of 30-70% (V / V).

5. A cosmetic, pharmaceutical, or quasi-drug containing an Enterococcus bacterium-induced skin inflammation inhibitor according to any one of claims 1 to 4.

6. The cosmetic, pharmaceutical, or quasi-drug according to claim 5, wherein the content of the extract of Isodon japonicus is 0.00001% by mass or more on a dry solid basis.

7. A method for suppressing Enterococcus-induced skin inflammation (excluding methods for treating humans), comprising the step of applying an extract of Isodon japonicus to the skin.

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