Composition for preventing or treating acne comprising strain isolated from skin of healthy adult

Abstract

The present invention relates to use of a strain isolated from the skin of a healthy adult for preventing, alleviating, and treating acne. When the strain of the present invention is used, acne can be effectively prevented, alleviated, and treated.

Description

A composition for the prevention or treatment of acne comprising a strain isolated from the skin of a healthy adult.

[0001] The present invention was carried out under Project No. 1415187757 with the support of the Ministry of Trade, Industry and Energy of the Republic of Korea, the research management agency for the said project is the Korea Institute for Industrial Technology Evaluation and Management, the research project name is "Bio-industry Technology Development Project," the research project name is "Development of Human Microbiome Immunotherapy Technology for Hidradenitis Suppurativa and Severe Acne Based on Microbiome-Multiomics Integrated Analysis," the lead organization is the Yonsei University Industry-Academic Cooperation Foundation, and the research period is April 1, 2023 - December 31, 2025.

[0002] This patent application claims priority to Korean Patent Application No. 10-2024-0174874, filed with the Korean Intellectual Property Office on November 29, 2024, the disclosures of said patent application are incorporated herein by reference.

[0003] The present invention relates to the use of strains isolated from the skin of healthy adults for the prevention, improvement, and treatment of acne.

[0004]

[0005] Acne is one of the most common skin conditions, experienced by approximately 80% of the entire population. It primarily occurs in areas rich in sebaceous glands, such as the face, neck, and chest, and begins with the accumulation of excess sebum produced in the hair follicles. This process is accelerated by hormonal changes, bacterial infections, genetic factors, and environmental factors.

[0006] One of the main causes of acne is P. acnes (Propionibacterium acnes), which is present in hair follicles and is currently classified as Cutibacterium acnes. This bacterium breaks down sebum in the sebaceous glands and produces free fatty acids. The generated free fatty acids trigger an inflammatory response and cause damage to the tissues surrounding the hair follicle, leading to the development of acne lesions.

[0007] Conventional acne treatments utilize antibiotics and disinfectants such as benzoyl peroxide. However, these treatments pose problems, including the emergence of resistant bacteria and side effects such as allergic contact dermatitis, erythema, and skin irritation. Additionally, there is a risk of reduced therapeutic efficacy or skin barrier damage with long-term use.

[0008] To address these issues, microbial-based therapies, such as probiotics, are gaining attention. Probiotics consist of beneficial microorganisms that regulate the balance of the skin microbial community, inhibit the growth of pathogenic microorganisms, and alleviate inflammation. In particular, probiotics can complement the shortcomings of existing chemical or antibiotic-based treatments by strengthening the skin barrier and exerting natural anti-inflammatory effects.

[0009] Therefore, there is a need to develop new treatments containing bacteria or microorganisms to overcome the limitations of existing treatments and provide a safer and more effective acne treatment.

[0010]

[0011] The inventors have made diligent research efforts to develop an effective method for preventing, improving, or treating acne. As a result, the present invention was completed by identifying the excellent acne treatment effect of a strain isolated from a healthy person.

[0012] Accordingly, the object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0013] Another objective of the present invention is to provide a food composition for preventing or improving acne comprising the above strain.

[0014] Another objective of the present invention is to provide a cosmetic composition for preventing or improving acne comprising the strain.

[0015] Another objective of the present invention is to provide a feed composition for the prevention or improvement of acne comprising the above strain.

[0016] Another objective of the present invention is to provide an antimicrobial composition against Cutibacterium acnes comprising the strain said above.

[0017] Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims, and drawings.

[0018]

[0019] The present invention provides the inventions of 1 to 13 below.

[0020] 1. A pharmaceutical composition for the prevention or treatment of acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0021] 2. A food composition for preventing or improving acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0022] 3. A cosmetic composition for preventing or improving acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0023] 4. A feed composition for the prevention or improvement of acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0024] 5. An antimicrobial composition for Cutibacterium acnes comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0025] 6. A method for treating acne comprising the step of administering to a subject requiring treatment one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi, or a composition containing such strains.

[0026] 7. Use in the manufacture of a pharmaceutical agent for the prevention or treatment of acne using one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0027] 8. A composition, a therapeutic method, or a use, wherein in any one of 1 to 7, the composition comprises Staphylococcus epidermidis and Streptococcus salivarius; Staphylococcus epidermidis and Dermacoccus profundi; Streptococcus salivarius and Dermacoccus profundi; or Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0028] 9. A composition, treatment method, or use, wherein in any one of 1 to 8, the Staphylococcus epidermidis is Staphylococcus epidermidis BS47C-1 (accession number: KCTC18886P), the Streptococcus salivarius is Streptococcus salivarius BS320F-4 (accession number: KCTC18885P), or the Dermacoccus profundi is Dermacoccus profundi BS35F-3 (accession number: KCTC18883P).

[0029] 10. A composition, a therapeutic method, or a use, wherein in any one of 1 to 9, the Staphylococcus epidermidis comprises the 16S rRNA sequence of SEQ ID NO. 1, the Streptococcus salivarius comprises the 16S rRNA sequence of SEQ ID NO. 2, or the Dermacoccus profundi comprises the 16S rRNA sequence of SEQ ID NO. 3.

[0030] 11. A composition, treatment method, or use, wherein in any one of 1 to 10, the strain inhibits inflammation.

[0031] 12. A composition, a therapeutic method, or a use, wherein in any one of 1 to 11, the strain is a live strain, a dead strain, an inactivated strain, a culture of the strain, a concentrate of the culture, a dried product of the culture, a pulverized product of the strain, an extract of the strain, a metabolite of the strain, a supernatant of the culture, or a combination thereof.

[0032] 13. A composition in any one of 1 to 12, wherein the composition additionally comprises a carrier suitable for a pharmaceutical composition, a food composition, a feed composition, or a cosmetic composition.

[0033]

[0034] In one aspect of the present invention, the present invention provides a pharmaceutical composition for the prevention or treatment of acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0035] The inventors have made diligent research efforts to develop an effective method for preventing, improving, or treating acne. As a result, they have identified the excellent acne treatment effect of a strain isolated from a healthy person.

[0036] In this specification, the term "Staphylococcus epidermidis" refers to a Gram-positive coccus, a commensal bacterium that is mainly found on the skin and mucous membranes. This strain is usually harmless to healthy people and can produce antimicrobial peptides or various physiologically active substances, so related research is being conducted.

[0037] In this specification, the term "Streptococcus salivarius" refers to a Gram-positive coccus that primarily inhabits the oral cavity and upper respiratory tract. This strain is commonly found in the human mouth and throat and, in most cases, acts as a harmless symbiotic bacterium. This strain is known to produce antimicrobial substances capable of inhibiting the growth of pathogenic bacteria in the mouth, and research is primarily being conducted on its effects in improving oral health.

[0038] In this specification, the term "Dermacoccus profundi" refers to a Gram-positive bacterium belonging to the genus Dermacoccus. The potential of said strain to produce antibiotics or other useful physiologically active substances is being studied.

[0039] In this specification, the term "acne" refers to an inflammatory skin disease of the follicular sebaceous glands manifesting as various skin lesions, such as closed or open comedones, papules, pustules, cysts, and nodules, on the face, upper chest, back, and upper extremities. The main causes of acne include excessive sebum secretion, abnormal follicular keratinization, proliferation of Cutibacterium acnes, and inflammation, and other hormonal or immunological factors may also be involved. These factors act in combination to cause acne lesions.

[0040] In this specification, the culture method, extraction method, isolation method, concentration method, drying method, dilution method, etc. for the cells of the strain are not particularly limited. The medium for culturing the cells may be an EG medium; an LB medium; an RCM medium; and / or a medium comprising one or more components selected from blood plate, maltose, sucrose, glucose, starch, mannitol, gelatin, casein, skim milk, other sugars, and yeast extract; various general aerobic or anaerobic methods may be appropriately used as the culture method; the culture temperature of the strain may be set to 30°C to 40°C, and a neutralization culture method may be used during culture to maintain the pH of the medium from neutral to acidic, for example, to a pH of 5 to 6, by using ammonia water. In addition to the neutralization culture method described above, any other culture method, such as batch culture, may be used. After culture, the culture or its supernatant may be concentrated, dried, or diluted as needed. Additionally, the supernatant of the culture and the bacterial cells may be separated using centrifugation or membrane separation, and the bacterial cells may be recovered in a concentrated state. Furthermore, components within the bacterial cells may be extracted by performing ultrasonic treatment or enzyme treatment on the bacterial cells, or the culture, its supernatant, the bacterial cells, or their extracts may be dried. These may be used as active ingredients of the above-mentioned composition.

[0041] In this specification, the term “prevention” means the prevention or protective treatment of a disease or diseased state. In this specification, the term “treatment” means the reduction, suppression, soothing, or eradication of a diseased state.

[0042] The pharmaceutical composition of the present invention may be prepared in a unit volume form or contained in a multi-dose container by formulation using a pharmaceutically acceptable carrier and / or excipient, according to a method that can be easily carried out by a person skilled in the art to which the invention belongs. In this case, the formulation may be in the form of a solution, suspension, or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, suppository, powder, granule, tablet, or capsule, and may additionally include a dispersant or a stabilizer.

[0043] In one embodiment of the present invention, the pharmaceutical composition of the present invention is in the form of a topical formulation. The topical formulation is not particularly limited but may be a powder, gel, ointment, cream, liquid, or aerosol formulation.

[0044] In this specification, one or more selected from Carbopol, Carbomer, Polyethylene glycol, Polypropylene glycol, Polyacrylic acid, Carboxymethyl cellulose, Hydroxymethyl cellulose, Polyvinyl pyrrolidone, Gelatin, Alginate Salt, Chitin or Chitosan derivatives, Hyaluronic acid, and Collagen may be used as the gel base for the external skin formulation, but are not limited thereto.

[0045] The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers are those commonly used in formulations and include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition to the above components, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

[0046] The pharmaceutical composition of the present invention may be administered orally or parenterally, for example by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, intrasternal injection, intratumoral injection, local administration, intranasal administration, intrapulmonary administration, and rectal administration.

[0047] Suitable dosages of the pharmaceutical composition of the present invention vary depending on factors such as the formulation method, mode of administration, patient's age, body weight, sex, pathological condition, food, time of administration, route of administration, rate of excretion, and response sensitivity, and a physician of ordinary skill can easily determine and prescribe a dosage effective for the desired treatment or prevention. According to a preferred embodiment of the present invention, the daily dosage of the composition of the present invention is 0.0001-100 mg / kg.

[0048] In one embodiment of the present invention, the Staphylococcus epidermidis is Staphylococcus epidermidis BS47C-1 (accession number: KCTC18886P), the Streptococcus salivarius is Streptococcus salivarius BS320F-4 (accession number: KCTC18885P), or the Dermacoccus profundi is Dermacoccus profundi BS35F-3 (accession number: KCTC18883P).

[0049] In one embodiment of the present invention, the Staphylococcus epidermidis comprises the 16S rRNA sequence of SEQ ID NO. 1, the Streptococcus salivarius comprises the 16S rRNA sequence of SEQ ID NO. 2, or the Dermacoccus profundi comprises the 16S rRNA sequence of SEQ ID NO. 3.

[0050] In one embodiment of the present invention, the strain inhibits inflammation.

[0051] In one embodiment of the present invention, it was confirmed that an inflammation indicator improved when treated with the strain of the present invention. The inflammation indicator may be, for example, Cox-2, iNOS, TNF-α, IL-1β, IL-6, or IL-8, but is not limited thereto. The improvement in the inflammation indicator may be due to the suppression of the expression of proteins or genes that induce or are related to inflammation.

[0052] The acne prevention or treatment and inflammation suppression effects of the above-mentioned strain are superior compared to other strains of the same species.

[0053] In this specification, the term “gene expression” may refer to the transcription of a gene into a polynucleotide, translation into a polypeptide, or modification of a polynucleotide and / or polypeptide (e.g., including post-translational modification of a polypeptide). The expressed gene includes a gene that is transcribed as mRNA and subsequently translated into a polypeptide, or transcribed into RNA but not translated into a polypeptide (e.g., tRNA and rRNA).

[0054] In this specification, the term “inhibition of gene or protein expression” means a case where the quantitative expression value of a gene or protein in a test group is reduced to a measurable level compared to a control group. For example, it may mean a case where the expression amount of a gene or protein in a test group is 90% or less, 80% or less, or 70% or less compared to a control group, but is not limited thereto.

[0055] In one embodiment of the present invention, the strain is a live strain, a dead strain, an inactivated strain, a culture of the strain, a concentrate of the culture, a dried product of the culture, a crushed product of the strain, an extract of the strain, a metabolite of the strain, a supernatant of the culture, or a combination thereof.

[0056] As used herein, the term "dead body" refers to a microorganism in a state where it has been completely killed using physical or chemical methods. In this process, the pathogenicity or vitality of the microorganism is eliminated, but its antigenicity is maintained, so it can induce an immune response.

[0057] Additionally, as used herein, the term "inactivated organism" refers to a microorganism in which the vitality of a pathogen has been inactivated by chemical, physical, or other methods. In this process, the microorganism can no longer multiply or cause infection, but its core structure capable of inducing an immune response remains intact.

[0058] In one embodiment of the present invention, the dead or inactivated cells of the strain may be obtained through one or more treatment methods selected from the group consisting of heat, freezing, drying, formaldehyde, glutaraldehyde, ethylene oxide, sodium hydroxide, beta-propiolactone, alcohol, ultraviolet rays, and gamma rays, but are not limited thereto.

[0059] In one embodiment of the present invention, the composition may be a probiotic composition containing beneficial bacteria. The term "probiotics" in this specification refers to live microorganisms that can provide beneficial effects to health when consumed in sufficient quantities. Most probiotics known to date are lactic acid bacteria, which can perform beneficial functions such as breaking down food in the intestines and synthesizing vitamins after reaching the intestines.

[0060] The composition of the present invention may be in powder form, and if in powder form, it may be coated in capsule form or may not be coated. In addition, the composition may be used in the form of oral formulations such as tablets, hard or soft capsules, liquids, suspensions, etc., and these formulations may be prepared using an acceptable conventional carrier, for example, in the case of oral formulations, excipients, binders, disintegrants, lubricants, solubilizers, suspending agents, preservatives, or volume extenders.

[0061] Methods for processing bacteria to provide live bacterial preparations are well known in the art, and as long as the bacteria are in a living form, the form of provision is not particularly limited. For example, after culturing the bacteria, the cell pellet may be recovered and used as is or processed by a desired means, such as by concentration and / or freeze-drying, to be added to the manufacture of pharmaceutical or edible products. Sometimes, immobilization or encapsulation processes may be performed to improve the shelf life of the live bacterial preparation. Techniques for immobilizing or encapsulating bacteria are known in the art.

[0062]

[0063] In one aspect of the present invention, the present invention provides a food composition for preventing or improving acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0064] The above food composition for preventing or improving acne has commonalities with the above pharmaceutical composition in that it contains one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi, and to avoid excessive duplication of description in the specification, descriptions of the overlapping scope are omitted.

[0065] The above food may be a health functional food, a health food, or a food additive, and in this case, there are no special restrictions on the type of food. Examples of the above food include drinks, meat, sausage, bread, biscuits, rice cakes, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, alcoholic beverages, vitamin complexes, dairy products and dairy processed products, etc., and include all health functional foods and health food compositions in the conventional sense, such as in the form of tablets, capsules, pills, or liquids.

[0066] The health functional food, health food, and food additive compositions containing the strain according to the present invention may be added to food as is or used together with other food or food ingredients, and may be used appropriately according to conventional methods.

[0067] In this specification, the amount of the composition in the health functional food, health food, or food additive may be added in an amount of 0.1 to 90 parts by weight of the total food weight. However, in the case of long-term consumption for the purpose of maintaining health or controlling health, the amount may be less than or equal to the above range.

[0068] In this specification, there are no special limitations on other ingredients added in addition to containing the strain mentioned above, and various flavoring agents or natural carbohydrates, etc., may be included as additional ingredients, as in ordinary beverages. Examples of the natural carbohydrates mentioned above include monosaccharides, e.g., glucose, fructose, etc.; disaccharides, e.g., maltose, sucrose, etc.; and polysaccharides, e.g., dextrin, cyclodextrin, etc., which are common sugars, and sugar alcohols such as xylitol, sorbitol, erythritol, etc. As flavoring agents other than those mentioned above, natural flavoring agents such as taumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.), and synthetic flavoring agents (saccharin, aspartame, etc.) may be advantageously used. The proportion of the natural carbohydrates may generally be about 1g to 20g, preferably about 5g to 12g, per 100g of the composition of the health functional food, health food, or food additive of the present invention.

[0069] In this specification, the food composition containing the strain may contain various nutritional supplements, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the health functional food and health food composition of the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice beverages and vegetable beverages.

[0070] In one embodiment of the present invention, the composition is prepared in any one formulation selected from powder, granules, pills, tablets, capsules, candies, syrups, and beverages. However, it is not limited thereto and can be prepared in various forms of food formulations.

[0071]

[0072] In one aspect of the present invention, the present invention provides a cosmetic composition for preventing or improving acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0073] The above cosmetic composition for preventing or improving acne has commonalities with the above pharmaceutical composition in that it contains one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi, and to avoid excessive duplication of description in the specification, descriptions of the overlapping scope are omitted.

[0074] The cosmetic composition of the present invention may be prepared in any formulation conventionally manufactured in the art, for example, as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation, and spray, but is not limited thereto. More specifically, it may be prepared in the form of a softening lotion, a nourishing lotion, a lotion, a nourishing cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray, or a powder.

[0075] The cosmetic composition of the present invention may include a carrier acceptable in a cosmetic formulation in addition to the active ingredient. The term "carrier acceptable in a cosmetic formulation" refers to an additional ingredient that is known and used to be included in a cosmetic formulation and can improve the application of the active ingredient to the skin, user convenience, and preference without significantly attenuating the main efficacy of the active ingredient or causing adverse effects on the human body.

[0076] The above carrier may be included in an amount of about 1% to about 99.99% by weight, preferably about 50% to about 99% by weight, based on the total weight of the composition of the present invention. However, the content of the above carrier may be appropriately adjusted according to the formulation of the cosmetic, the specific application site, and the preferred amount of application, and is not particularly limited.

[0077] In the case where the formulation of the composition of the present invention is a paste, cream, lotion, or gel, a carrier

[0078] Animal oils, vegetable oils, waxes, paraffins, starch, tragacanth gum, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide may be used as ingredients.

[0079] In the case where the formulation of the composition of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, it may additionally include a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

[0080] When the formulation of the composition of the present invention is a solution or an emulsion, a solvent, a solubilizing agent, or an emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan.

[0081] When the formulation of the composition of the present invention is a suspension, liquid diluents such as water, ethanol, or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agatos or tragacanth gum, etc. may be used as carrier components.

[0082] In the case where the formulation of the composition of the present invention is a surfactant-containing cleansing agent, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester, etc. may be used as a carrier component.

[0083] In addition to the active ingredient and the carrier ingredient, the ingredients included in the cosmetic composition of the present invention include ingredients commonly used in cosmetic compositions, and may include, for example, conventional auxiliary agents such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and fragrances.

[0084]

[0085] In one aspect of the present invention, the present invention provides a feed composition for preventing or improving acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0086] The above feed composition may include feed or feed additives for feeding a diet to animals.

[0087] When the strain of the present invention is used in a feed composition or a feed additive composition, the composition may be prepared as a highly concentrated liquid of 20 to 90% or in the form of a powder or granules. The feed additive may additionally include one or more of organic acids such as citric acid, fumaric acid, adipic acid, lactic acid, and malic acid, phosphates such as sodium phosphate, potassium phosphate, and acidic pyrophosphate, or natural antioxidants such as polyphenols, catechins, alpha-tocopherol, rosemary extract, vitamin C, green tea extract, licorice extract, chitosan, tannic acid, and phytic acid.

[0088] In the present specification, when the strain is used as feed, the composition may be formulated in the form of a conventional feed and may include conventional feed ingredients. The feed additive and feed may further include grains, for example, ground or crushed wheat, oats, barley, corn, and rice; plant protein feed, for example, feed with rapeseed, soybeans, and sunflowers as the main ingredients; animal protein feed, for example, blood meal, meat meal, bone meal, and fish meal; sugars and dairy products, for example, dried ingredients consisting of various milk powders and whey powders; and may further include nutritional supplements, digestion and absorption enhancers, growth promoters, etc.

[0089] In this specification, when the strain is used as the feed additive, it may be administered to animals alone or in combination with other feed additives among edible carriers. Additionally, the feed additive may be easily administered to animals as a top dressing, by mixing directly into animal feed, or as an oral formulation separate from the feed. When the feed additive is administered separately from animal feed, it may be prepared as an immediate-release or sustained-release tablet formulation by combining it with a pharmaceutically acceptable edible carrier, as is well known in the art. Such edible carriers may be solid or liquid, for example, corn starch, lactose, sucrose, soybean flakes, peanut oil, olive oil, sesame oil, and propylene glycol. When a solid carrier is used, the feed additive may be a tablet, capsule, powder, lozenge, sugar-containing tablet, or a finely dispersed top dressing. When a liquid carrier is used, the feed additive may be a gelatin soft capsule, or in the form of a syrup, suspension, emulsion, or solution. The above feed may include any protein-containing organic grain meal commonly used to satisfy the dietary needs of animals. Such protein-containing grain meal typically consists of corn, soybean meal, or a corn / soybean meal mix. Additionally, the feed composition may contain, for example, preservatives, stabilizers, wetting agents or emulsifiers, solution accelerators, etc. Furthermore, the feed additive composition may be used by adding it to the animal feed by immersion, spraying, or mixing.

[0090] The subjects of the feed or feed additive of the present invention are individuals requiring prevention or improvement of acne, and said individuals may include all animals excluding humans who have or may develop acne, and said animals may include non-human primates, e.g., chimpanzees, other ape or monkey species; livestock animals, e.g., cattle, horses, sheep, goats, pigs; domesticated animals, e.g., rabbits, dogs, or cats; laboratory animals, e.g., rodents, e.g., rats, mice, or guinea pigs; non-mammalians, e.g., birds or fish, etc., but are not limited thereto.

[0091] The above-mentioned feed composition for the prevention or improvement of acne has commonalities with the above-mentioned pharmaceutical composition in that it comprises one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi, and the description of the overlapping scope is omitted to avoid excessive duplication of description in the specification.

[0092]

[0093] In one aspect of the present invention, the present invention provides an antimicrobial composition for Cutibacterium acnes comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0094] The above antimicrobial composition against Cutibacterium acnes has commonalities with the above pharmaceutical composition in that it comprises one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi, and to avoid excessive duplication of descriptions in the specification, descriptions of the overlapping scope are omitted.

[0095] In the present invention, "Cutibacterium acnes (C. acnes)" is a Gram-positive bacterium that resides within hair follicles and is one of the causative agents of acne. The lipolytic enzyme secreted by Cutibacterium acnes breaks down fatty acids secreted by the sebaceous glands to form free fatty acids, stimulates the hair follicles, and contributes to the inflammatory response of acne.

[0096] In this specification, the term "antimicrobial" means an activity that prevents or treats bacterial infection by inhibiting the growth or proliferation of bacteria, including microorganisms.

[0097]

[0098] In one aspect of the present invention, the present invention provides a method for treating acne comprising the step of administering to a subject requiring treatment one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi, or a composition comprising such strains.

[0099] The above treatment method has commonalities with the contents of the composition described above in that it includes one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi, and to avoid excessive duplication of description in the specification, descriptions of the overlapping scope are omitted.

[0100] In one aspect of the present invention, the present invention provides a use in the manufacture of a pharmaceutical agent for preventing or treating acne, comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0101] The above use has commonalities with the contents of the composition described above in that it includes one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi, and to avoid excessive duplication of description in the specification, descriptions of the overlapping scope are omitted.

[0102]

[0103] The features and advantages of the present invention are summarized as follows:

[0104] (a) The present invention provides a pharmaceutical composition for the prevention or treatment of acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

[0105] (b) The present invention provides a food composition for preventing or improving acne comprising the above strain.

[0106] (c) The present invention provides a cosmetic composition for preventing or improving acne comprising the strain.

[0107] (d) The purpose of the present invention is to provide a feed composition for the prevention or improvement of acne comprising the strain.

[0108] (e) The present invention provides an antimicrobial composition against Cutibacterium acnes comprising the strain above.

[0109] (f) When using the strain of the present invention, acne can be effectively prevented, improved, and treated.

[0110]

[0111] Figure 1 shows the results of API 20A kit analysis of three strains isolated from the skin of a healthy adult.

[0112] Figure 2 shows the results of the analysis of the antibacterial effects of three live bacterial strains isolated from the skin of a healthy adult.

[0113] Figure 3 shows the results of the analysis of the antibacterial effect of three dead bacterial strains isolated from the skin of a healthy adult.

[0114] Figures 4a to 4f show the results of the analysis of the anti-inflammatory effects of three strains isolated from the skin of healthy adults.

[0115] Figure 5 shows the results of an in vivo analysis of the acne-improving effects of three strains isolated from the skin of healthy adults.

[0116] Figures 6a to 6f show the results of analyzing the anti-inflammatory effects of three strains isolated from the skin of healthy adults in vivo.

[0117]

[0118] The present invention will be described in more detail below through examples. These examples are intended solely to explain the invention more specifically, and it will be obvious to those skilled in the art that the scope of the invention is not limited by these examples according to the gist of the invention.

[0119]

[0120] Examples

[0121] Example 1: Identification of strains and analysis of mycological characteristics

[0122] Three strains, Staphylococcus epidermidis BS47C-1 (accession number: KCTC18886P), Streptococcus salivarius BS320F-4 (accession number: KCTC18885P), and Dermacoccus profundi BS35F-3 (accession number: KCTC18883P), were isolated from the skin of healthy adults.

[0123] The mycological characteristics of the strains are shown in Table 1, the results of the API 20A kit analysis are shown in Figure 1, and the results of the MIC (Minimum Inhibitory Concentration) test are shown in Table 2. The 16s rRNA sequences of the three strains are shown in SEQ ID NOs 1 to 3.

[0124]

[0125] Mycological characteristics of the strains Item S. epidermidis BS47C-1 S. salivarius BS320F-4 D. profundi BS35F-3 Gram stain Gram-positive Gram-positive Gram-positive Morphology Cocci Cocci Colony Color Milky white Milky white Yellow Oxygen required Aerobic Facultative Anaerobic Aerobic

[0126]

[0127] MIC test result antibiotic EFSA standard S. epidermidis BS47C-1S. salivarius BS320F-4D. profundi BS35F-3Ampicillin180.750.25Vancomycin210.750.25Gentamicin0.2580.750.5Kanamycin0.56484Streptomy cin4261.5Erythromycin16120.250.5Clindamycin80.0640.0640.25Tetracycline212244Chloramphenicol2821

[0128]

[0129]

[0130] As shown in Table 2, the MIC test results showed that S. epidermidis BS47C-1 exhibited values ​​exceeding the EFSA threshold for ampicillin, gentamicin, kanamycin, tetracycline, and chloramphenicol, while S. salivarius BS320F-4 showed values ​​exceeding the EFSA threshold for gentamicin, kanamycin, streptomycin, and tetracycline. D. profundi BS35F-3 also showed values ​​exceeding the EFSA threshold for gentamicin, kanamycin, and tetracycline. To confirm the possibility that such antibiotic resistance could be transmitted via gene transfer, whole genome sequencing analysis of the three bacterial species revealed no IS elements or phages capable of transferring the resistance around the antibiotic resistance genes. Consequently, it was determined that the likelihood of such antibiotic resistance being transmitted to the host was extremely low.

[0131]

[0132] Example 2: Analysis of antibacterial effect against acne-causing bacteria (in vitro)

[0133] 2-1. Antimicrobial Effects of Live Strains (3 Types)

[0134] Cutibacterium acnes (C. acnes), known as an acne-causing strain, and an effective strain were inoculated together into Reinforced Clostridial Broth and cultured at 37°C for 3 days. After culture, the number of viable C. acnes was analyzed, and the extent to which the growth of C. acnes was inhibited by treatment with the effective strain compared to the control group (PBS-treated group) was determined.

[0135] The results are shown in Figure 2.

[0136] As shown in Figure 2, SE strain showed a growth inhibition rate of 38.0%, SS showed 10.8%, and Ye showed 11.4%.

[0137]

[0138] 2-3. Antimicrobial Effects of Inactivated Cells from Three Strains

[0139] Heat-treated dead cells of C. acnes, known as an acne-causing strain, and effective strains were inoculated together into Reinforced Clostridial Broth and cultured at 37°C for 3 days. After culture, the number of viable C. acnes cells was analyzed, and the extent to which the growth of C. acnes was inhibited by treatment with effective strains compared to the control group (PBS-treated group) was determined.

[0140] The results are shown in Figure 3.

[0141] As shown in Figure 3, the SE strain showed a growth inhibition rate of 19.9%, SS showed 13.2%, and the example showed a growth inhibition rate of 13.4%.

[0142]

[0143] 2-3. Analysis of Anti-inflammatory Effects of Three Strains

[0144] Inflammation was induced in keratinocytes by administering C. acnes, and then the anti-inflammatory efficacy was confirmed by administering inactivated cells of three effective strains. Specifically, the mRNA expression levels of six inflammatory markers—Cox-2, iNOS, TNF-α, IL-1β, IL-6, and IL-8—were confirmed via RT-qPCR.

[0145] The results are shown in Figures 4a to 4f and Table 3.

[0146] As shown in Figures 4a to 4f and Table 3, it was confirmed that the mRNA expression levels of Cox-2, iNOS, TNF-α, IL-1β, IL-6, and IL-8 in the group administered with inactivated effective strains were significantly reduced compared to the control group administered with C. acnes alone.

[0147]

[0148] Anti-inflammatory effects of 3 strains COX2iNOSTNF-αControl 1.0002 ± 0.0217 1.0002 ± 0.0180 1.0009 ± 0.0426 Acne 1.8699 ± 0.0462 2.4444 ± 0.1793 1.9509 ± 0.1507 SE 1.2298 ± 0.0089 1.2498 ± 0.0248 0.9306 ± 0.0195 SS 1.0801 ± 0.0293 1.2685 ± 0.0754 0.6791 ± 0.0206 DP 1.5049 ± 0.0183 1.6056 ± 0.1356 1.3468 ± 0.0547IL-1βIL-6IL-8Control1.0004 ± 0.02791.0001 ± 0.01331.0029 ± 0.0759Acne1.7927 ± 0.04252.0374 ± 0.03562.1654 ± 0.0447SE0.8574 ± 0.00691.2683 ± 0.07131.3454 ± 0.0132SS0.6380 ± 0.02740.8784 ± 0.03111.0102 ± 0.0318DP1.1313 ± 0.01981.8159 ± 0.06111.4238 ± 0.0560

[0149]

[0150] Example 3: Analysis of acne improvement effect (in vivo)

[0151] To analyze the acne-improving effect of the strains of the present invention, the hair on the backs of 6-week-old female CD-1 mice was removed, and acne was induced by intradermally injecting C. acnes, an acne-inducing strain, into both sides of the back daily for 2 weeks. After inducing acne, 50 µL of inactivated cells of three strains were applied to the affected area once a day for one week. The condition of the affected area was observed visually before the application of the inactivated cells and after the application was completed.

[0152] The results are shown in Figure 5.

[0153] As shown in Figure 5, visual inspection of the affected area revealed persistent swelling and erythema in the affected area of ​​the control group injected with C. acnes. In contrast, the test group, which had dead cells of three effective strains applied for one week, showed a noticeable reduction in swelling and improved erythema compared to the control group.

[0154]

[0155] RNA was extracted from the dorsal skin tissue of the aforementioned experimental animals to synthesize cDNA, and the mRNA expression levels of Cox-2, iNOS, TNF-α, IL-1β, IL-6, and IL-8 were confirmed by quantitative RT-PCR.

[0156] The results are shown in Figures 6a to 6f and Table 4.

[0157] As shown in Figures 6 to 6f and Table 4, it was confirmed that the mRNA expression levels of inflammation markers were significantly reduced compared to the control group.

[0158]

[0159] Anti-inflammatory effects of 3 strains COX2iNOSTNF-αControl 1.0006 ± 0.0360 1.0001 ± 0.0167 1.0002 ± 0.0199 Acne 1.1923 ± 0.0166 1.3089 ± 0.0078 3.0024 ± 0.0307 SE 0.5666 ± 0.0150 0.7046 ± 0.0238 1.9159 ± 0.0544 SS 0.8966 ± 0.0068 0.8068 ± 0.1017 1.3920 ± 0.0399 DP 0.6604 ± 0.0174 0.9593 ± 0.0020 1.9725 ± 0.0921IL-1βIL-6IL-8Control1.0003 ± 0.02591.0014 ± 0.05331.0018 ± 0.0588Acne1.4255 ± 0.04581.0562 ± 0.00881.8316 ± 0.0238SE0.7179 ± 0.01340.7631 ± 0.02401.1506 ± 0.0794SS0.7923 ± 0.05590.8066 ± 0.03790.9181 ± 0.0767DP0.6021 ± 0.05500.7667 ± 0.05960.7216 ± 0.0138

[0160]

[0161] Trustee number

[0162] Depository Name: Korea Research Institute of Biotechnology and Bioengineering Biological Resource Center (KCTC)

[0163] Trustee Number: KCTC18883P

[0164] Date of Trust: 20210126

[0165]

[0166] Depository Name: Korea Research Institute of Biotechnology and Bioengineering Biological Resource Center (KCTC)

[0167] Trustee Number: KCTC18885P

[0168] Date of Trust: 20210126

[0169]

[0170] Depository Name: Korea Research Institute of Biotechnology and Bioengineering Biological Resource Center (KCTC)

[0171] Trustee Number: KCTC18886P

[0172] Date of Trust: 20210126

[0173] [Correction pursuant to Rule 91 Dec. 31, 2025]

[0174] [Correction pursuant to Rule 91 Dec. 31, 2025]

[0175] [Correction pursuant to Rule 91 Dec. 31, 2025]

Claims

1. A pharmaceutical composition for the prevention or treatment of acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

2. A pharmaceutical composition for the prevention or treatment of acne according to claim 1, wherein the Staphylococcus epidermidis is Staphylococcus epidermidis BS47C-1 (Accession No.: KCTC18886P), the Streptococcus salivarius is Streptococcus salivarius BS320F-4 (Accession No.: KCTC18885P), or the Dermacoccus profundi is Dermacoccus profundi BS35F-3 (Accession No.: KCTC18883P).

3. A pharmaceutical composition for the prevention or treatment of acne according to claim 1, wherein the Staphylococcus epidermidis comprises the 16S rRNA nucleotide sequence of SEQ ID NO. 1, the Streptococcus salivarius comprises the 16S rRNA nucleotide sequence of SEQ ID NO. 2, or the Dermacoccus profundi comprises the 16S rRNA nucleotide sequence of SEQ ID NO.

3.

4. A pharmaceutical composition for the prevention or treatment of acne, wherein, in claim 1, the strain inhibits inflammation.

5. A pharmaceutical composition for the prevention or treatment of acne according to claim 1, wherein the strain is a live bacterium, a dead bacterium, an inactivated bacterium, a culture of the strain, a concentrate of the culture, a dried product of the culture, a pulverized product of the strain, an extract of the strain, a metabolite of the strain, a supernatant of the culture, or a combination thereof.

6. A food composition for preventing or improving acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

7. A cosmetic composition for preventing or improving acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

8. A feed composition for the prevention or improvement of acne comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

9. An antimicrobial composition for Cutibacterium acnes comprising one or more strains selected from the group consisting of Staphylococcus epidermidis, Streptococcus salivarius, and Dermacoccus profundi.

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