Composition for treating tinea capitis

Abstract

Provided is a novel composition for treating tinea capitis. The composition for treating white ringworm contains at least one selected from the group consisting of a human staphylococcus strain, a hemolytic staphylococcus strain, and a Staphylococcus vorus strain.

Description

Technical Field

[0001] The present invention relates to a composition for treating white ringworm, etc. Background Art

[0002] Tinea tinea is a skin infection caused by fungi of the genus Trichophyton (so-called white ringworm). According to the site of onset, tinea tinea is classified into tinea pedis (tinea pedis), tinea unguium (tinea nails), tinea manuum (tinea hand), tinea corporis (tinea corporis), tinea cruris (tinea groin), tinea capitis (tinea head), etc.

[0003] White ringworm is infected by the white ringworm patients have the white ringworm fungus. For example, in the high incidence of tinea pedis (tinea pedis) and tinea unguium (tinea unguium), etc., the white ringworm fungus existing in swimming pools, baths, restaurants, slippers, etc. is known to be the main infection route.

[0004] Trichophyton is a transient fungus that parasitizes in the keratin or subcutaneous tissue of the skin. If the trichophyton proliferates and erodes into the stratum corneum, inflammation or blisters will occur, resulting in symptoms such as itching. It should be noted that trichophyton uses keratin, which is the main component of keratin, as a nutrient source.

[0005] Conventionally, antifungal drugs such as itraconazole, miconazole, clotrimazole, ketoconazole, bifonazole, lanoconazole, luliconazole, efinaconazole, flusaconaazole, terbinafine, butenafine, etc. have been used as therapeutic drugs for tinea vitiligo.

[0006] For example, the following is recorded in non-patent document 1: Among prepubertal children, the incidence of tinea corporis (tinea corporis) and tinea capitis (tinea capitis) is relatively high. On the other hand, among young people and adults, the incidence of tinea corporis (tinea corporis), tinea cruris (tinea groin), and tinea pedis (tinea pedis) is relatively high. Since there are diseases that show the same clinical symptoms, it is sometimes preferred to diagnose through potassium hydroxide preparations or culture, and the therapeutic drug can be appropriately selected from creams or oral agents, etc.

[0007] In addition, Patent Document 1 discloses an invention relating to an external preparation for treating onychomycosis, comprising a) an antifungal active substance, b) a volatile component, c) a medium-chain fatty acid triglyceride, and d) ethyl lactate. According to the external preparation disclosed in Patent Document 1, it is disclosed that the external preparation has excellent characteristics from the viewpoints of nail permeability, drug efficacy, and preparation properties by using medium-chain fatty acid triglyceride as a non-volatile component and ethyl lactate as a permeation enhancer.

[0008] It should be noted that Patent Document 1 describes that an external preparation for treating onychomycosis is superior to an oral preparation in that it has fewer systemic side effects and drug interactions.

[0009] Prior art literature

[0010] Patent Literature

[0011] Patent document 1: International Publication No. 2019 / 088005.

[0012] Non-patent literature

[0013] Non-patent document 1: American Family Physician, Volume 90, Number 10, 702-711. Summary of the invention

[0014] Problems to be solved by the invention

[0015] Under such circumstances, further development of therapeutic drugs for tinea versicolor is underway.

[0016] Means of solving problems

[0017] The present invention provides, for example, the following composition for treating tinea versicolor.

[0018] [1] A composition for treating tinea versicolor, comprising at least one selected from the group consisting of Staphylococcus hominis strains, Staphylococcus haemolyticus strains, and Staphylococcus warneri strains.

[0019] [2] The composition for treating tinea versicolor according to [1] above, comprising a Staphylococcus aureus strain.

[0020] [3] The composition for treating tinea versicolor according to [2] above, wherein the human Staphylococcus aureus strain has a 16s rDNA comprising the base sequence of SEQ ID NO: 1 or a 16s rDNA comprising a base sequence having 95% or more identity with SEQ ID NO: 1, and has an anti-tinea versicolor effect.

[0021] [4] The composition for treating tinea versicolor according to [2] or [3] above, wherein the human Staphylococcus aureus strain comprises at least one selected from the group consisting of human Staphylococcus aureus ATCC27844, human Staphylococcus aureus ATCC27845, human Staphylococcus aureus ATCC700236 and human Staphylococcus aureus A9 (ATCC Accession No.: PTA-125203).

[0022] [5] The composition for treating tinea versicolor according to any one of [1] to [4] above, comprising a hemolytic Staphylococcus aureus strain.

[0023] [6] The composition for treating tinea versicolor according to the above [5], wherein the hemolytic Staphylococcus aureus strain has a 16s rDNA comprising the base sequence of SEQ ID NO: 10 or a 16s rDNA comprising a base sequence having 95% or more identity with SEQ ID NO: 10, and has an anti-tinea versicolor effect.

[0024] [7] The composition for treating tinea versicolor according to [5] or [6] above, wherein the hemolytic Staphylococcus aureus strain contains at least one selected from the group consisting of Staphylococcus aureus ATCC29970, Staphylococcus aureus ATCC700564 and Staphylococcus aureus ATCC29969.

[0025] [8] The composition for treating tinea versicolor according to any one of [1] to [7] above, comprising a Staphylococcus woermannii strain.

[0026] [9] The composition for treating tinea versicolor according to [8] above, wherein the Staphylococcus woersii strain has a 16s rDNA comprising the base sequence of SEQ ID NO: 17 or a 16s rDNA comprising a base sequence having 95% or more identity with SEQ ID NO: 17, and has an anti-tinea versicolor effect.

[0027]

[10] The composition for treating tinea versicolor according to [8] or [9] above, wherein the Staphylococcus woersii strain contains Staphylococcus woersii ATCC27836.

[0028]

[11] The composition for treating tinea tinea according to any one of [1] to

[10] above, wherein the pathogenic bacteria of tinea tinea comprises a fungus of the genus Trichophyton.

[0029]

[12] The composition for treating tinea versicolor according to the above

[11] , wherein the pathogenic bacteria of tinea versicolor comprises at least one fungal strain selected from the group consisting of Trichophyton rubrum, Trichophyton mentagrophytes and Trichophyton tonsurans.

[0030]

[13] The composition for treating tinea vitiligo according to any one of [1] to

[12] above, which is an external preparation.

[0031]

[14] A method for producing a composition for treating tinea versicolor, comprising:

[0032] A step (1) of collecting bacterial flora from at least one of a person's ankle and sole and culturing the bacterial flora,

[0033] The step (2) of isolating and culturing the cultured bacterial flora to obtain candidate bacteria,

[0034] step (3) of evaluating the anti-Trichophyton activity of the candidate bacteria to identify bacteria having anti-Trichophyton activity, and

[0035] Step (4) of preparing a composition for treating tinea versicolor containing the bacteria having anti-tinea versicolor activity;

[0036] The bacteria having the anti-Trichophyton effect contains at least one selected from the group consisting of Staphylococcus aureus strains, hemolytic Staphylococcus aureus strains and Staphylococcus woertzii strains.

[0037] Effects of the Invention

[0038] According to the present invention, a novel composition for treating tinea versicolor is provided. According to a preferred embodiment of the present invention, the composition can be used even when the artificial chemical synthesis and extraction of the drug compound are difficult or when the drug efficacy is based on the life reaction derived from living bacteria, and can have one or more of the following effects: preventing or reducing side effects, preventing or inhibiting rashes around the affected area, improving skin adhesion, maintaining relief, preventing recurrence, reducing the number of applications, improving compliance, and achieving higher therapeutic effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] [ Figure 1 ]Typical examples of various evaluations of anti-Trichophyton effects.

[0040] [ Figure 2 ] A graph showing the results of the anti-Trichophyton activity of each strain of candidate bacteria (91 strains) obtained from ankles and soles.

[0041] [ Figure 3 ] Phylogenetic tree of known and candidate bacteria of the genus Staphylococcus.

[0042] [ Figure 4 ] Phylogenetic tree of known and candidate Staphylococci.

[0043] [ Figure 5 ]Phylogenetic tree of known and candidate hemolytic Staphylococci. DETAILED DESCRIPTION

[0044] Hereinafter, the present invention will be described in detail.

[0045] <Composition for treating tinea tinea>

[0046] The composition for treating white ringworm of the present invention contains at least one selected from the group consisting of Staphylococcus aureus, Staphylococcus hemolyticus and Staphylococcus vorus. The composition for treating white ringworm of the present invention can treat white ringworm. It should be noted that in this specification, "treating" means preventing or inhibiting the proliferation of Trichophyton fungi (so-called white ringworm) to kill bacteria or inhibit bacteria.

[0047] It is known that there are individual differences in the onset and recurrence of white ringworm. The inventors predicted that the individual differences lie in the skin-resident bacteria, and studied the effects of the skin-resident bacteria and known strains of Staphylococcus collected from the ankles (ankles) and soles of healthy people on white ringworm. As a result, it was found that the human Staphylococcus (hereinafter also referred to as "human Staphylococcus (S.hominis)") strain, hemolytic Staphylococcus (hereinafter also referred to as "hemolytic Staphylococcus (S.haemolyticus)") strain and Wollstein Staphylococcus (hereinafter also referred to as "Wollstein Staphylococcus (S.warneri)") strain, which are skin-resident bacteria, are effective in the treatment of white ringworm. According to the present invention, a new composition for the treatment of white ringworm can be provided.

[0048] It should be noted that since Staphylococcus aureus, Staphylococcus hemolyticus and Staphylococcus woertz are bacteria that normally live on the skin, they have few or no side effects. Therefore, for example, it is possible to prevent or suppress rashes on the skin around the affected area that may occur with conventional external preparations.

[0049] In addition, since Staphylococcus aureus, Staphylococcus hemolyticus, and Staphylococcus woertz are skin-resident bacteria, they are easily attached to the skin. Therefore, for example, compared with conventional external preparations, the effects on the affected part of the skin can be prolonged and the number of applications can be reduced.

[0050] In addition, since Staphylococcus aureus, Staphylococcus hemolyticus and Staphylococcus woertz are living bacteria that normally live on the skin, they can have therapeutic effects even when artificial chemical synthesis and extraction of the drug compound are difficult or when the drug efficacy is based on a life reaction derived from living bacteria.

[0051] Therefore, the composition for treating tinea versicolor according to the present invention can have the effects of having fewer side effects, excellent compliance, and showing higher effects, etc., compared with other external preparations.

[0052] [Staphylococcus aureus strains]

[0053] In one embodiment, the composition for treating tinea tinea contains a Staphylococcus hominis strain.

[0054] Staphylococcus aureus strains are coagulase negative staphylococci (CNS) and Gram-positive bacteria. Staphylococcus aureus strains are skin-resident bacteria. It is speculated that Staphylococcus aureus strains kill or inhibit Trichophyton by directly or indirectly damaging Trichophyton, competing for living sites, etc., thereby preventing or inhibiting the proliferation or fixation of Trichophyton.

[0055] The human Staphylococcus strain preferably includes a human Staphylococcus strain having an anti-trichophyton effect. That is, in a preferred embodiment, a composition for treating tinea versicolor comprising a human Staphylococcus strain having an anti-trichophyton effect is provided. It should be noted that, in this specification, "anti-trichophyton effect" means that when the anti-trichophyton effect is evaluated by the method described in "4. Evaluation of anti-trichophyton effect" of the examples, the evaluation result is "++" or "+", preferably "++". Therefore, the human Staphylococcus strain having an anti-trichophyton effect can treat tinea versicolor.

[0056] As human Staphylococcus aureus strain, there is no particular limitation, and preferably a strain having a 16s rDNA containing a base sequence of sequence number 1 or a 16s rDNA containing a base sequence having 95% or more identity with sequence number 1 and having an anti-tinea vitiligo effect. As shown in the Examples, sequence number 1 is a base sequence of a region sandwiched by two common sequences shared by 16s rDNA of the genus Staphylococcus. At this time, of the above two common sequences, the common sequence on the 5' side is common sequence 1 (AGCTTGC), and the common sequence on the 3' side is common sequence 2 (AAGCTGG), which are included in sequence number 1. Here, for example, "a 16s rDNA containing a base sequence of sequence number 1" means having a base sequence of sequence number 1 in the base sequence of 16s rDNA. It should be noted that in this specification, the base sequences of sequence numbers 1 to 18 can be determined by the method described in the Examples. In addition, in the case where a certain bacterium has more than two types of 16s rDNA, the 16s rDNA with the highest content is the 16s rDNA of the bacterium. When containing the same number of two or more types of 16s rDNA, for human Staphylococcus aureus strains, the 16s rDNA with the base sequence having the highest identity with sequence number 1 is used as the 16s rDNA of the bacterium, for hemolytic Staphylococcus aureus strains, the 16s rDNA with the base sequence having the highest identity with sequence number 10 is used as the 16s rDNA of the bacterium, and for Staphylococcus vorusii strains, the 16s rDNA with the base sequence having the highest identity with sequence number 17 is used as the 16s rDNA of the bacterium.

[0057] A base sequence having 95% or more identity with SEQ ID NO: 1 preferably has 96% or more, 96.5% or more, 97% or more, 97.5% or more, 98% or more, 98.1% or more, 98.2% or more, 98.3% or more, 98.4% or more, 98.5% or more, 98.6% or more, 98.7% or more, 98.8% or more, 98.9% or more, 99% or more, 99.1% or more, 99.2% or more, 99.3% or more, 99.4% or more, 99.5% or more, 99.6% or more, 99.7% or more, 99.8% or more, or 99.9% or more identity with SEQ ID NO: 1.

[0058] Examples of mutations in a base sequence having 95% or more identity with SEQ ID NO: 1 include substitution, deletion, insertion, addition, and combinations thereof. In a preferred embodiment, the number of substitutions, deletions, insertions, additions, and combinations thereof is preferably 1 to 10, more preferably 1 to 5, and even more preferably 1 to 2.

[0059] The above-mentioned substitution is not particularly limited, and is preferably selected from at least one of guanine at position 45, thymine at position 139, thymine at position 140, adenine at position 309, and cytosine at position 1265 of sequence number 1. It should be noted that, in one embodiment, guanine at position 45 of sequence number 1 may be substituted by adenine (45G>A (also expressed as G45A)), thymine at position 139 may be substituted by cytosine (139T>C), thymine at position 140 may be substituted by cytosine (140T>C), adenine at position 309 may be substituted by cytosine (309A>C), and cytosine at position 1265 may be substituted by thymine (1265C>T).

[0060] The deletion is not particularly limited, and adenine at position 488 of SEQ ID NO: 1 (488delA (may also be expressed as A488Δ)) may be deleted.

[0061] The insertion is not particularly limited, and may be inserted between positions 1182 and 1183 and between positions 1235 and 1236 of sequence number 1. It should be noted that, in one embodiment, adenine (1182_1183insA (also represented as Δ1183A)) may be inserted between positions 1182 and 1183 of sequence number 1, and guanine (1235_1236insG) may be inserted between positions 1235 and 1236.

[0062] In addition, the base sequence having 95% or more identity with the above-mentioned sequence number 1 may be a base sequence retained by a human Staphylococcus strain by natural mutation, etc., or a base sequence obtained by artificial mutation treatment. It should be noted that, as artificial mutation treatment, for example, methods such as gene manipulation, genome editing, ultraviolet irradiation, radiation irradiation, ethyl methanesulfonate (MES) treatment, N-methyl-N-nitrosoguanidine (NTG) treatment, nitrous acid treatment, etc. can be listed. These mutation treatments can be used alone or in combination of two or more.

[0063] Examples of base sequences having 95% or more identity with SEQ ID NO: 1 include SEQ ID NOs: 2 to 9. The mutation sites of SEQ ID NOs: 2 to 9 are shown in Table 1 below.

[0064] [Table 1]

[0065] Serial Number Mutation site based on sequence number 1 Sequence Number 1 - Sequence number 2 139T>C, 140T>C Sequence number 3 1265C>T Sequence Number 4 140T>C Sequence number 5 45G>A Sequence Number 6 45G>A, 309A>C Sequence Number 7 45G>A, 488delA Sequence Number 8 45G>A, 1182_1183insA Sequence Number 9 45G>A, 1235_1236insG

[0066] The Staphylococcus aureus strain having 16s rDNA containing the base sequence of SEQ ID NO: 1 is not particularly limited, and examples thereof include Staphylococcus aureus ATCC27844 and Staphylococcus aureus ATCC27845.

[0067] Examples of Staphylococcus aureus strains having 16s rDNA containing a base sequence having 95% or more identity with SEQ ID NO: 1 and having anti-tinea vitiligo activity include, but are not particularly limited to, Staphylococcus aureus ATCC700236 and Staphylococcus aureus A9 (ATCC accession number: PTA-125203).

[0068] In one embodiment, as human Staphylococcus strains, there are no particular limitations, and examples thereof include human Staphylococcus ATCC27844, human Staphylococcus ATCC27845, human Staphylococcus ATCC700236, human Staphylococcus FDAARGOS_748, human Staphylococcus J6, human Staphylococcus FDAARGOS_136, human Staphylococcus A9 (ATCC commission number PTA-125203), human Staphylococcus C2, human Staphylococcus AMT2, human Staphylococcus AMT3, human Staphylococcus AMT4-C2, human Staphylococcus AMT4-G1, human Staphylococcus AMT4-D12, etc. In addition to the above, as strains belonging to human Staphylococcus, "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet

[0069] <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 2014 / > The strains described in . Among them, the strains belonging to human Staphylococcus preferably include at least one selected from human Staphylococcus ATCC27844, human Staphylococcus ATCC27845, human Staphylococcus ATCC700236, human Staphylococcus FDAARGOS_748, human Staphylococcus J6, human Staphylococcus FDAARGOS_136 and human Staphylococcus A9, and more preferably include at least one selected from human Staphylococcus ATCC27844, human Staphylococcus ATCC27845, human Staphylococcus ATCC700236 and human Staphylococcus A9. It should be noted that the above-mentioned human Staphylococcus strains can be used alone or in combination of two or more.

[0070] Human Staphylococcus aureus strains with anti-trichophyton effect can be easily prepared by the following method. Specifically, the preparation method of human Staphylococcus aureus strains with anti-trichophyton effect includes: a step (1) of collecting bacterial flora from at least one of the ankles and soles of a person (preferably a healthy person without symptoms of tinea versicolor) and culturing them; a step (2) of isolating and culturing the above-cultured bacterial flora to obtain candidate bacteria; and a step (3) of evaluating the anti-trichophyton effect of the above-mentioned candidate bacteria to determine the bacteria with anti-trichophyton effect. Each step will be described later. The bacterial flora of the ankles and soles of a person usually contains strains of human Staphylococcus aureus that are known to be skin-resident bacteria. Moreover, according to the above method, strains of human Staphylococcus aureus with anti-trichophyton effect can be easily prepared.

[0071] The concentration of Staphylococcus aureus strain in the composition for treating white ringworm is preferably 10 3 ~10 11 CFU / g, more preferably 10 4 ~10 10 CFU / g, more preferably 10 5 ~10 9 CFU / g. It should be noted that, in this specification, "CFU" means colony forming unit (Colony Forming Unit). In addition, in this specification, the concentration (CFU / g) of the bacterial strain in the composition for treating white ringworm is calculated by diluting the composition for treating white ringworm to an appropriate concentration, applying it on an agar medium for bacterial culture, and measuring the colonies that appear after culture (refer to Clinical Microbiology Procedures Handbook volume 2 third edition).

[0072] The form of the human Staphylococcus aureus strain in the composition for treating tinea versicolor is not particularly limited, but is preferably in the form of a dry powder (eg, a freeze-dried form, a spray-dried form).

[0073] [Hemolytic Staphylococcus aureus strains]

[0074] In one embodiment, the composition for treating tinea tinea contains a hemolytic Staphylococcus aureus strain.

[0075] Hemolytic Staphylococcus aureus is a coagulase negative staphylococcus (CNS) and a gram-positive bacterium. Hemolytic Staphylococcus aureus is a skin resident bacterium. Hemolytic Staphylococcus aureus is also presumed to kill or inhibit the proliferation of Trichophyton by directly or indirectly damaging Trichophyton aureus or competing for living sites.

[0076] The hemolytic Staphylococcus aureus strain preferably includes a hemolytic Staphylococcus aureus strain having an anti-trichophyton effect. That is, in a preferred embodiment, a composition for treating tinea versicolor comprising a hemolytic Staphylococcus aureus strain having an anti-trichophyton effect is provided. The hemolytic Staphylococcus aureus strain having an anti-trichophyton effect can treat tinea versicolor.

[0077] As a hemolytic Staphylococcus strain, there is no particular limitation, but preferably a strain having a 16s rDNA containing a base sequence of sequence number 10 or a 16s rDNA containing a base sequence having 95% or more identity with sequence number 10 and having an anti-tinea vitiligo effect. As shown in the Examples, sequence number 10 is a base sequence of a region sandwiched by two consensus sequences shared by 16s rDNA of the genus Staphylococcus. At this time, of the above two consensus sequences, the consensus sequence on the 5' side is consensus sequence 1 (AGCTTGC), and the consensus sequence on the 3' side is consensus sequence 2 (AAGCTGG), which are included in sequence number 10. Here, for example, "a 16s rDNA containing a base sequence of sequence number 10" means that the base sequence of 16s rDNA has a base sequence of sequence number 10.

[0078] A base sequence having 95% or more identity with sequence number 10 preferably has 96% or more, 96.5% or more, 97% or more, 97.5% or more, 98% or more, 98.1% or more, 98.2% or more, 98.3% or more, 98.4% or more, 98.5% or more, 98.6% or more, 98.7% or more, 98.8% or more, 98.9% or more, 99% or more, 99.1% or more, 99.2% or more, 99.3% or more, 99.4% or more, 99.5% or more, 99.6% or more, 99.7% or more, 99.8% or more, or 99.9% or more identity with sequence number 10.

[0079] Examples of mutations in a base sequence having 95% or more identity with SEQ ID NO: 10 include substitutions, deletions, insertions, additions, and combinations thereof. In a preferred embodiment, the number of substitutions, deletions, insertions, additions, and combinations thereof is preferably 1 to 10, more preferably 1 to 5, and even more preferably 1 to 2.

[0080] The above-mentioned substitution is not particularly limited, and is preferably at least one selected from the group consisting of cytosine at position 96, guanine at position 109, adenine at position 398, cytosine at position 952, and cytosine at position 1186 of sequence number 10. It should be noted that, in one embodiment, cytosine at position 96 of sequence number 10 may be substituted by thymine (96C>T), guanine at position 109 may be substituted by adenine (109G>A), adenine at position 398 may be substituted by guanine (398A>G), and cytosine at position 1186 may be substituted by thymine (1186C>T).

[0081] The above-mentioned deletion is not particularly limited, and the adenine at position 1210 (1210delA), the adenine at position 1219 (1219delA), the thymine at position 1225 (1225delT), and the adenine at position 1263 (1263delA) of sequence number 10 may be deleted.

[0082] The above insertion is not particularly limited, and may be inserted between positions 1117 and 1118, between positions 1195 and 1196, and between positions 1234 and 1235 of sequence number 10. It should be noted that, in one embodiment, guanine (1117_1118insG) may be inserted between positions 1117 and 1118 of sequence number 10, cytosine (1195_1196insC) may be inserted between positions 1195 and 1196, and guanine (1234_1235insG) may be inserted between positions 1234 and 1235.

[0083] The base sequence having 95% or more identity with the above-mentioned sequence number 10 is also the same as that of human Staphylococcus aureus strains, and may be a base sequence retained by other hemolytic Staphylococcus aureus strains through natural mutation, etc., or a base sequence obtained by artificial mutation treatment. It should be noted that, as artificial mutation treatment, for example, methods such as gene manipulation, genome editing, ultraviolet irradiation, radiation irradiation, ethyl methanesulfonate (MES) treatment, N-methyl-N-nitrosoguanidine (NTG) treatment, nitrous acid treatment, etc. can be listed. These mutation treatments can be used alone or in combination of two or more.

[0084] Examples of base sequences having 95% or more identity with SEQ ID NO: 10 include SEQ ID NOs: 11 to 16. The mutation sites of SEQ ID NOs: 11 to 16 are shown in Table 2 below.

[0085] [Table 2]

[0086]

[0087] The Staphylococcus aureus strain having 16s rDNA containing the base sequence of SEQ ID NO: 10 is not particularly limited, and examples thereof include Staphylococcus aureus ATCC29970 and Staphylococcus aureus ATCC700564.

[0088] In one embodiment, the hemolytic Staphylococcus aureus strain is not particularly limited, and examples thereof include hemolytic Staphylococcus aureus ATCC29970, hemolytic Staphylococcus aureus ATCC700564, hemolytic Staphylococcus aureus ATCC29969, hemolytic Staphylococcus aureus SH_12, and hemolytic Staphylococcus aureus JCSC1435. In addition to the above, as the hemolytic Staphylococcus aureus strain, "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet

[0089] <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 1141 / > The strains described in . Among them, the hemolytic Staphylococcus strains preferably include at least one selected from the group consisting of hemolytic Staphylococcus ATCC29970, hemolytic Staphylococcus ATCC700564, hemolytic Staphylococcus ATCC29969, hemolytic Staphylococcus SH_12, and hemolytic Staphylococcus JCSC1435, and more preferably include at least one selected from the group consisting of hemolytic Staphylococcus ATCC29970, hemolytic Staphylococcus ATCC700564, and hemolytic Staphylococcus ATCC29969. It should be noted that the above-mentioned hemolytic Staphylococcus strains can be used alone or in combination of two or more.

[0090] The hemolytic Staphylococcus aureus strain with anti-trichophyton effect is the same as the human Staphylococcus aureus strain and can be easily prepared by the following method. Specifically, the preparation method of the hemolytic Staphylococcus aureus strain with anti-trichophyton effect includes: a step (1) of collecting bacterial flora from at least one of the ankles and soles of a person (preferably a healthy person without symptoms of tinea versicolor) and culturing them; a step (2) of isolating and culturing the above-cultured bacterial flora to obtain candidate bacteria; and a step (3) of evaluating the anti-trichophyton effect of the above-mentioned candidate bacteria to determine the bacteria with anti-trichophyton effect. The hemolytic Staphylococcus aureus strain with anti-trichophyton effect can also be included in the bacterial flora of the ankles and soles of humans. Therefore, according to the above method, a hemolytic Staphylococcus aureus strain with anti-trichophyton effect can be easily prepared.

[0091] The concentration of the hemolytic Staphylococcus aureus strain in the composition for treating white ringworm is preferably 10 3 ~10 11 CFU / g, more preferably 10 4 ~10 10 CFU / g, more preferably 10 5 ~10 9 CFU / g.

[0092] The form of the hemolytic Staphylococcus aureus strain in the composition for treating tinea tinea is not particularly limited, but is preferably in a dry powder form (eg, freeze-dried form, spray-dried form).

[0093] [Staphylococcus vorticella]

[0094] In one embodiment, the composition for treating tinea tinea contains a strain of Staphylococcus woermannii.

[0095] Staphylococcus wolleri strains are coagulase negative staphylococci (CNS) and Gram-positive bacteria. Staphylococcus wolleri strains are skin-resident bacteria. It is speculated that Staphylococcus wolleri strains also prevent or inhibit the proliferation of Trichophyton by directly or indirectly damaging Trichophyton, competing for living sites, etc., and thus kill or inhibit fungi.

[0096] The Staphylococcus wolleri strain preferably includes a Staphylococcus wolleri strain having an anti-trichophyton effect. That is, in a preferred embodiment, a composition for treating tinea versicolor comprising a Staphylococcus wolleri strain having an anti-trichophyton effect is provided. The Staphylococcus wolleri strain having an anti-trichophyton effect can treat tinea versicolor.

[0097] The strain of Staphylococcus vorticella is not particularly limited, but preferably has a 16s rDNA containing a base sequence of sequence number 17 or a 16s rDNA containing a base sequence having 95% or more identity with sequence number 17 and has an anti-tinea vitiligo effect. As shown in the Examples, sequence number 17 is a base sequence of a region sandwiched by two consensus sequences shared by 16s rDNA of the genus Staphylococcus. At this time, of the two consensus sequences, the consensus sequence on the 5' side is consensus sequence 1 (AGCTTGC), and the consensus sequence on the 3' side is consensus sequence 2 (AAGCTGG), which are included in sequence number 17. Here, for example, "16s rDNA containing a base sequence of sequence number 17" means that the base sequence of 16s rDNA has a base sequence of sequence number 17.

[0098] A base sequence having 95% or more identity with sequence number 17 preferably has 96% or more, 96.5% or more, 97% or more, 97.5% or more, 98% or more, 98.1% or more, 98.2% or more, 98.3% or more, 98.4% or more, 98.5% or more, 98.6% or more, 98.7% or more, 98.8% or more, 98.9% or more, 99% or more, 99.1% or more, 99.2% or more, 99.3% or more, 99.4% or more, 99.5% or more, 99.6% or more, 99.7% or more, 99.8% or more, or 99.9% or more identity with sequence number 17.

[0099] Examples of mutations in a base sequence having 95% or more identity with SEQ ID NO: 17 include substitutions, deletions, insertions, additions, and combinations thereof. In a preferred embodiment, the number of substitutions, deletions, insertions, additions, and combinations thereof is preferably 1 to 10, more preferably 1 to 5, and even more preferably 1 to 2.

[0100] The above-mentioned substitution is not particularly limited, but is preferably cytosine at position 52 of sequence number 17. It should be noted that, in one embodiment, cytosine at position 52 of sequence number 17 may be substituted with guanine (52C>G).

[0101] The base sequence having 95% or more identity with the above-mentioned sequence number 17 is also the same as that of human Staphylococcus aureus strains, and may be a base sequence retained by other Staphylococcus aureus strains through natural mutation, or may be a base sequence obtained through artificial mutation treatment. It should be noted that, as artificial mutation treatment, for example, methods such as gene manipulation, genome editing, ultraviolet irradiation, radiation irradiation, ethyl methanesulfonate (MES) treatment, N-methyl-N-nitrosoguanidine (NTG) treatment, nitrous acid treatment, etc. can be listed. These mutation treatments can be used alone or in combination of two or more.

[0102] An example of a base sequence having 95% or more identity with SEQ ID NO: 17 is SEQ ID NO: 18. The mutation site of SEQ ID NO: 18 is shown in Table 3 below.

[0103] [Table 3]

[0104] Serial Number Mutation site based on SEQ ID No. 17 Sequence Number 17 - Sequence Number 18 52C>G

[0105] The Staphylococcus worderi strain having 16s rDNA containing the base sequence of SEQ ID NO: 17 is not particularly limited, and Staphylococcus worderi ATCC27836 is exemplified.

[0106] In one embodiment, the strain of Staphylococcus wolleri is not particularly limited, and examples thereof include Staphylococcus wolleri ATCC27836, Staphylococcus wolleri NCTC7291, Staphylococcus wolleri WB224, Staphylococcus wolleri 16A, Staphylococcus wolleri 22.1, and the like. In addition to the above, as the strain of Staphylococcus wolleri, "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet<https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 2073 / > The strains described in . Among them, the Staphylococcus wolleri strain preferably includes at least one selected from Staphylococcus wolleri ATCC27836, Staphylococcus wolleri NCTC7291, Staphylococcus wolleri WB224, Staphylococcus wolleri 16A, Staphylococcus wolleri 22.1 and Staphylococcus wolleri WS479, and more preferably includes Staphylococcus wolleri ATCC27836. It should be noted that the above-mentioned Staphylococcus wolleri strains can be used alone or in combination of two or more.

[0107] The Staphylococcus wolleri strain with anti-trichophyton effect is the same as the human Staphylococcus strain and can be easily prepared by the following method. Specifically, the preparation method of the Staphylococcus wolleri strain with anti-trichophyton effect includes: a step (1) of collecting bacterial flora from at least one of the ankle and sole of a person (preferably a healthy person without symptoms of tinea versicolor) and culturing it; a step (2) of isolating and culturing the above-cultured bacterial flora to obtain candidate bacteria; and a step (3) of evaluating the anti-trichophyton effect of the above-mentioned candidate bacteria to determine the bacteria with anti-trichophyton effect. The Staphylococcus wolleri strain with anti-trichophyton effect can also be included in the bacterial flora of the ankle and sole of a person. Therefore, according to the above method, the Staphylococcus wolleri strain with anti-trichophyton effect can be easily prepared.

[0108] The concentration of Staphylococcus aureus in the composition for treating white ringworm is preferably 10 3 ~10 11 CFU / g, more preferably 10 4 ~10 10 CFU / g, more preferably 10 5 ~10 9 CFU / g.

[0109] The form of the Staphylococcus woermannii strain in the composition for treating tinea versicolor is not particularly limited, but is preferably in the form of a dry powder (eg, a freeze-dried form, a spray-dried form).

[0110] [Other Staphylococcus strains]

[0111] The composition for treating tinea tinea may further contain other Staphylococcus strains. Here, "Staphylococcus strains" means Staphylococcus strains other than Staphylococcus hominis, Staphylococcus haemolyticus and Staphylococcus woertz.

[0112] Other Staphylococcus strains are not particularly limited, and examples include strains reported to be isolated from humans, such as Staphylococcus saprophyticus, Staphylococcus kloosii, Staphylococcus lugdunensis, Staphylococcus capitis, Staphylococcus caprae, Staphylococcus epidermidis, and Staphylococcus aureus.

[0113] As the saprophytic Staphylococcus (S. saprophyticus) strain, there can be listed "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet<https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 1350 / > The strains recorded in .

[0114] Examples of the Staphylococcus kloosii strain include "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet<https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 66884 / > The strains recorded in .

[0115] Examples of the S. lugdunensis strain include "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet<https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 2548 / > The strains recorded in .

[0116] As the Staphylococcus capitis (S. capitis) strain, there can be listed "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet<https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 2054 / > The strains recorded in .

[0117] As the strain of Staphylococcus caprae, there can be cited "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet<https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 1971 / > The strains recorded in .

[0118] Examples of the Staphylococcus epidermidis strain include "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet<https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 155 / > The strains recorded in .

[0119] Examples of Staphylococcus aureus (S. aureus) strains include "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet<https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 154 / > The strains recorded in .

[0120] As other Staphylococcus strains, from the viewpoint of obtaining a higher white ringworm treatment effect, it is preferred to include at least one selected from Staphylococcus capitis, Staphylococcus capitis strains, Staphylococcus epidermidis strains, Staphylococcus krusei strains, Staphylococcus lugdunensis strains and Staphylococcus saprophyticus strains, more preferably at least one selected from Staphylococcus capitis strains and Staphylococcus capitis strains, and particularly preferably at least one selected from Staphylococcus capitis ATCC27840 and Staphylococcus capitis ATCC35538. In addition, from the viewpoint of adjusting the balance of skin resident bacteria in the affected part of the white ringworm treatment composition, other Staphylococcus strains preferably include Staphylococcus epidermidis strains, and further preferably include at least one selected from Staphylococcus epidermidis ATCC12228 and Staphylococcus epidermidis ATCC14990. It should be noted that these other Staphylococcus strains can be used alone or in combination of two or more.

[0121] The concentration of other Staphylococcus strains in the composition for treating tinea tinea is not particularly limited, but is preferably 10 3 ~10 11 CFU / g, more preferably 10 4 ~10 10 CFU / g, more preferably 10 5 ~10 9 CFU / g. In addition, when other Staphylococcus strains are contained in combination of two or more, it is preferable that the amount of each species of the two or more other Staphylococcus strains is within the above range.

[0122] The form of other Staphylococcus strains in the composition for treating tinea tinea is not particularly limited, and is preferably in a dry powder form (e.g., a freeze-dried form, a spray-dried form). It should be noted that the form of other Staphylococcus strains is preferably the same as at least one selected from the above-mentioned Staphylococcus hominis strains, Staphylococcus hemolyticus strains, and Staphylococcus woertzii strains.

[0123] [Other strains]

[0124] The composition for treating tinea tinea may further contain strains of other genera. Here, "strains of other genera" refers to bacterial strains other than Staphylococcus strains.

[0125] The strains of other genera are not particularly limited, but are preferably skin-resident bacteria (i.e., skin-resident bacteria other than Staphylococcus bacteria), and examples thereof include Cutibacterium acnes (acne bacteria) strains, Streptococcus pyogenes (group A β-hemolytic streptococcus) strains, Pseudomonas aeruginosa (Pseudomonas aeruginosa) strains, Escherichia coli strains, Bacillus cereus strains, Enterococcus faecalis strains, Moraxella osloensis strains, and the like.

[0126] Examples of the Propionibacterium acnes (acne bacteria) strain include "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet

[0127] <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 1140 / > The strains recorded in .

[0128] Examples of Streptococcus pyogenes (group A β-hemolytic streptococcus) strains include "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet

[0129] <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 175 / > The strains recorded in .

[0130] Examples of Pseudomonas aeruginosa (Pseudomonas aeruginosa) strains include "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet

[0131] <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 187 / > The strains recorded in .

[0132] As the Escherichia coli strain, there is NCBI, "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet

[0133] <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 167 / > The strains recorded in .

[0134] Examples of Bacillus cereus strains include "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet

[0135] <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 157 / > The strains recorded in .

[0136] Examples of Enterococcus faecalis strains include "NCBI", "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet

[0137] <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 808 / > The strains recorded in .

[0138] As the Moraxella osloensis strain, there is NCBI, "Online", deposited on February 17, 2022, [retrieved on February 17, 2022], Internet

[0139] <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 12468 / > The strains recorded in .

[0140] Among them, as strains of other genera, from the viewpoint of obtaining a higher effect of treating white ringworm, it is preferred to include at least one selected from Pseudomonas aeruginosa (Pseudomonas aeruginosa) strains, Escherichia coli strains, Bacillus cereus strains, Enterococcus faecalis strains, and Moraxella osloensis strains, more preferably at least one selected from Pseudomonas aeruginosa (Pseudomonas aeruginosa) strains, Escherichia coli strains, and Enterococcus faecalis strains, and further preferably at least one selected from Pseudomonas aeruginosa ATCC27853, Escherichia coli ATCC25922, and Enterococcus faecalis ATCC29212. In addition, as strains of other genera, from the viewpoint of adjusting the balance of skin-resident bacteria in the affected area of ​​the composition for treating white ringworm, it is preferred to include at least one selected from Proteobacterium acnes (acne bacteria) strains, Streptococcus pyogenes (Group A β-hemolytic Streptococcus) strains, and Pseudomonas aeruginosa (Pseudomonas aeruginosa) strains, more preferably Proteobacterium acnes (acne bacteria) strains, and further preferably Proteobacterium acnes ATCC6919. In addition, these strains of other genera may be used alone or in combination of two or more.

[0141] The concentration of other strains of the genus in the composition for treating tinea versicolor is not particularly limited, but is preferably 10 3 ~10 11 CFU / g, more preferably 10 4 ~10 10 CFU / g, more preferably 10 5 ~10 9 CFU / g. In addition, when two or more strains of other genus are contained in combination, it is preferable that each of the two or more strains of other genus is within the above range.

[0142] The form of the strains of other genera in the composition for treating tinea tinea is not particularly limited, and is preferably in a dry powder form (e.g., a freeze-dried form, a spray-dried form). It should be noted that the form of the strains of other genera is preferably the same as at least one selected from the above-mentioned Staphylococcus aureus strains, hemolytic Staphylococcus aureus strains, and Staphylococcus vorusii strains.

[0143] [Antifungal agents]

[0144] The composition for treating white ringworm may further contain an antifungal agent. By containing an antifungal agent, the therapeutic effect of white ringworm can be further improved.

[0145] The antifungal agent is not particularly limited, and examples thereof include itraconazole, miconazole, clotrimazole, ketoconazole, bifonazole, lanoconazole, luliconazole, efinaconazole, flusaconaazole, terbinafine, butenafine, etc. These antifungal agents may be used alone or in combination of two or more.

[0146] The concentration of the antifungal agent in the composition for treating tinea tinea is not particularly limited, but is preferably 0.1 to 30% by mass, more preferably 0.5 to 15% by mass, based on the total mass of the composition for treating tinea tinea.

[0147] [additive]

[0148] The composition for treating tinea tinea may further contain additives. The additives are not particularly limited, and examples of the additives include bases, wetting agents, thickeners, emulsifiers, co-emulsifiers, preservatives, stabilizers, pH adjusters, and the like.

[0149] (Matrix)

[0150] Examples of the matrix include hydrophobic matrix, hydrophilic matrix, and water. In the present specification, "matrix" refers to an additive having a content of 40% by mass or more, preferably 50 to 99% by mass, relative to the total mass of the composition for treating tinea tinea.

[0151] The hydrophobic matrix is ​​not particularly limited, and examples thereof include higher hydrocarbons such as squalane, liquid paraffin, light liquid paraffin, vaseline, ozokerite, microcrystalline wax, squalene, and gelled hydrocarbons; oils and fats such as olive oil, jojoba oil, sesame oil, soybean oil, cocoa butter, camellia oil, peanut oil, tallow, lard, triacetin, and hydrogenated castor oil; waxes such as beeswax, white beeswax, carnauba wax, and lanolin; fatty acids such as stearic acid and oleic acid, higher alcohols such as lanolin alcohol, myristyl alcohol, cetyl alcohol (cetyl alcohol), stearyl alcohol, cetearyl alcohol, and cholesterol, and fatty acid esters such as isopropyl myristate, stearyl myristate, and medium-chain fatty acid triglycerides.

[0152] The hydrophilic base is not particularly limited, and examples thereof include lower alcohols such as ethanol, propanol, and isopropanol; polyols such as glycerol, 1,3-butylene glycol, and propylene glycol; sugar alcohols such as sorbitol and mannitol; and polyethylene glycol.

[0153] The above-mentioned bases may be used alone or in combination of two or more.

[0154] (Wetting Agent)

[0155] The moisturizer keeps the skin moisturized when the composition for treating tinea tinea is applied.

[0156] The wetting agent is not particularly limited, and examples thereof include vaseline, glycerin, propylene glycol, and 1,3-butylene glycol.

[0157] The above-mentioned wetting agents may be used alone or in combination of two or more.

[0158] (Thickener)

[0159] The thickener increases the viscosity of the composition for treating tinea tinea or forms a gel.

[0160] The thickener is not particularly limited, and examples thereof include gelatin, agar, carrageenan, gum arabic, tragacanth, sodium alginate, propylene glycol alginate, acrylic acid polymers, polyvinyl alcohol (partially saponified), sodium alginate, methyl cellulose, carboxymethyl cellulose, water-soluble cellulose derivatives (hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and hydrophobized hydroxypropyl methyl cellulose), sodium polyacrylate, glycerol monooleate, pectin, xanthan gum, and the like.

[0161] The above thickeners may be used alone or in combination of two or more.

[0162] (Emulsifier)

[0163] The emulsifier emulsifies the composition for treating tinea tinea into an oil-in-water (o / w) type or a water-in-oil (w / o) type.

[0164] The emulsifier is not particularly limited, and examples thereof include cationic surfactants such as alkylamine salts, alkylamine polyoxyethylene adducts, fatty acid triethanolamine monoester salts, acylaminoethyldiethylamine salts, and fatty acid polyamine condensates; anionic surfactants such as polyoxyethylene alkyl ether phosphates, aminosulfates, saturated higher fatty acid salts, and N-acylamino acid salts; nonionic surfactants such as sucrose fatty acid esters, glycerol fatty acid esters, polyglycerol fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyethylene glycol, polyethylene glycol fatty acid esters, polyoxyethylene polyoxypropylene glycol, and polyoxyethylene alkyl ethers; and zwitterionic surfactants such as alkyl betaines, alkyl amide betaines, alkyl sulfobetaines, imidazolines, lauryl dimethylaminoacetic acid betaine, and alkyl diaminoethyl glycine.

[0165] The above emulsifiers may be used alone or in combination of two or more.

[0166] (Co-emulsifier)

[0167] The auxiliary emulsifier stabilizes the emulsification when the composition for treating tinea tinea is emulsified into an oil-in-water (o / w) type or a water-in-oil (w / o) type.

[0168] The auxiliary emulsifier is not particularly limited, and examples thereof include cetyl alcohol (cetyl alcohol), stearyl alcohol, oleyl alcohol, and isostearyl alcohol.

[0169] The above-mentioned auxiliary emulsifiers may be used alone or in combination of two or more.

[0170] (preservative)

[0171] The preservative prevents or inhibits contamination and decomposition of the composition for treating tinea versicolor caused by foreign microorganisms.

[0172] The preservative is not particularly limited, and examples thereof include p-hydroxybenzoic acid, methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, sodium benzoate, chlorobutanol, chlorocresol, benzyl alcohol, salicylic acid, phenoxyethanol, thymol, butylhydroxytoluene, sodium edetate hydrate, sodium dehydroacetate, sorbic acid, potassium sorbate, and benzalkonium chloride.

[0173] The above-mentioned preservatives may be used alone or in combination of two or more.

[0174] (Stabilizer)

[0175] The stabilizer prevents or inhibits the death, decomposition, and physical changes of the components contained in the composition for treating tinea tinea.

[0176] The stabilizer is not particularly limited, and examples thereof include sodium hydrogen sulfite, sodium pyrosulfite, ascorbic acid, tocopherol, dibutylhydroxytoluene, sodium edetate (EDTA), and benzotriazole.

[0177] The above stabilizers may be used alone or in combination of two or more.

[0178] (pH adjuster)

[0179] The pH adjuster maintains the stability of the components contained in the composition for treating tinea tinea, and prevents or reduces the stimulation of the composition for treating tinea tinea to the living body.

[0180] The pH adjuster is not particularly limited, and examples thereof include lactic acid, acetic acid, acetates (such as sodium acetate), citric acid, citrates (such as sodium citrate), phosphoric acid, phosphates (such as sodium phosphate), diisopropanolamine, triisopropanolamine, triethanolamine, potassium hydroxide, and sodium hydroxide.

[0181] The above pH adjusters may be used alone or in combination of two or more.

[0182] [Dosage form]

[0183] The dosage form of the composition for treating tinea tinea is not particularly limited, and is preferably an external preparation. By using the composition for treating tinea tinea as an external preparation, at least one selected from the group consisting of Staphylococcus aureus, Staphylococcus hemolyticus, and Staphylococcus woertzi can be attached to the skin, effectively preventing or inhibiting the proliferation or attachment of tinea tinea, and performing bactericidal or bacteriostatic treatment.

[0184] The specific form of the external preparation is not particularly limited, and examples thereof include ointments, creams, gels, lotions, and the like.

[0185] It should be noted that an ointment is a semisolid external preparation applied to the skin in which the active ingredient is dissolved or dispersed in a matrix, and examples thereof include oily ointments and water-soluble ointments. A cream is a semisolid external preparation applied to the skin that is emulsified into an oil-in-water (o / w) type or a water-in-oil (w / o) type. A gel is a gel-like external preparation applied to the skin, and examples thereof include aqueous gels and oily gels. A lotion is a liquid external preparation in which the active ingredient (human Staphylococcus aureus strain, hemolytic Staphylococcus aureus strain, Staphylococcus wolleri strain, etc.) is dissolved or dispersed in an aqueous solution.

[0186] [Trichophyton]

[0187] The pathogenic bacteria of white ringworm are Trichophyton, specifically, fungi of the genus Trichophyton. Examples of the above-mentioned Trichophyton include fungal strains of Trichophyton rubrum, Trichophyton mentagrophytes, and Trichophyton tonsurans.

[0188] Examples of the fungal strain of Trichophyton rubrum include Trichophyton rubrum ATCC28188 and Trichophyton rubrum ATCC22402.

[0189] Examples of the fungal strain of Trichophyton mentagrophytes include Trichophyton mentagrophytes TIMM2789 and Trichophyton mentagrophytes ATCC MYA-4439.

[0190] Examples of the fungal strain of Trichophyton tonsurans include Trichophyton tonsurans ATCC56186 and Trichophyton tonsurans ATCC28942.

[0191] The pathogenic bacteria of white ringworm preferably include fungi of the genus Trichophyton, more preferably include at least one selected from fungal strains of Trichophyton rubrum, fungal strains of Trichophyton mentagrophytes and fungal strains of Trichophyton tonsurans, further preferably include fungal strains of Trichophyton rubrum, and particularly preferably include Trichophyton rubrum ATCC 28188. It should be noted that the pathogenic bacteria of white ringworm may be one or more than two.

[0192] Tinea tinea is caused by the above-mentioned Trichophyton. It should be noted that, according to the site of onset, tinea pedis (tinea pedis), tinea unguium (tinea onychosum), tinea manuum (tinea hand), tinea corporis (tinea corporis), tinea cruris (tinea groin), tinea capitis (tinea capitis), etc. Since the skin permeability of the external preparation varies depending on the site of onset, it is preferred to appropriately adjust the composition of the external preparation according to the site of onset.

[0193] [Application method]

[0194] There is no particular limitation on the method of applying the composition for treating tinea tinea. When the composition for treating tinea tinea is an external preparation, it is applied to the affected part.

[0195] The number of applications (number of applications) is not particularly limited, and may be any one of 3 times a day, 2 times a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day. Wherein, the number of applications is preferably 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day, 1 time a day. The composition for treating tinea versicolor involved in the present invention contains at least one selected from human Staphylococcus aureus strains, hemolytic Staphylococcus aureus strains and Staphylococcus aureus strains with excellent skin fixation. Therefore, compared with conventional tinea versicolor therapeutic agents, the sustained effect of the fixation of live bacteria can be exerted, and remission can be maintained or recurrence can be prevented, and the number of applications can be reduced or the compliance of the patient can be improved.

[0196] When the composition for treating tinea tinea is applied externally, the application amount is preferably 0.1 to 180 mg / cm 2 , more preferably 1 to 10 mg / cm 2 At this time, the amount of at least one selected from the group consisting of Staphylococcus aureus, Staphylococcus hemolyticus and Staphylococcus vorusii in the composition for treating tinea tinea is preferably 10 0 ~10 8 CFU / cm 2 , more preferably 10 1 ~10 7 CFU / cm 2 , more preferably 10 2 ~10 6 CFU / cm 2 When the composition for treating tinea tinea contains two or more of the Staphylococcus aureus strain, the hemolytic Staphylococcus aureus strain, and the Staphylococcus vorusii strain, the total amount thereof is preferably within the above range.

[0197] The affected part to which the composition for treating tinea tinea is applied is not particularly limited, and is generally an affected part with symptoms of tinea tinea. It should be noted that the composition for treating tinea tinea of ​​the present invention contains at least one selected from the group consisting of Staphylococcus aureus, Staphylococcus hemolyticus, and Staphylococcus vorusii, which are skin-resident bacteria. Therefore, compared with conventional external preparations, the number of applications can be reduced due to high skin fixation, and the problem of rash on the skin around the affected part is not caused or hardly caused, and the patient's compliance can be improved.

[0198] The above-mentioned composition for treating tinea versicolor can exert a therapeutic effect by being used alone, or can be combined with other therapeutic agents.

[0199] As the above-mentioned other therapeutic agents, oral preparations and external preparations can be listed. In this case, the above-mentioned oral preparation or the above-mentioned external preparation contains at least one of antifungal drugs such as itraconazole, miconazole, clotrimazole, ketoconazole, bifonazole, lanoconazole, luliconazole, efinaconazole, flusaconaazole, terbinafine, butenafine, etc. The above-mentioned other therapeutic agents can also be combined with two or more.

[0200] That is, according to one embodiment of the present invention, a white ringworm therapeutic composition and a combination agent with other therapeutic agents are provided. At this time, when the white ringworm therapeutic composition is an external preparation, the other therapeutic agent is preferably an oral preparation. In addition, the white ringworm therapeutic composition and other therapeutic agents can be applied simultaneously or sequentially.

[0201] <Method for producing a composition for treating tinea versicolor>

[0202] According to one embodiment of the present invention, a method for manufacturing a composition for treating tinea versicolor is provided. The above-mentioned manufacturing method includes: a step (1) of collecting bacterial flora from at least one of the ankles and soles of a person (preferably a healthy person without tinea versicolor symptoms) and culturing the bacterial flora; a step (2) of isolating and culturing the above-mentioned cultivated bacterial flora to obtain candidate bacteria; a step (3) of evaluating the anti-tinea versicolor effect of the above-mentioned candidate bacteria and determining the bacteria with anti-tinea versicolor effect; and a step (4) of modulating a composition for treating tinea versicolor containing the bacteria with the above-mentioned anti-tinea versicolor effect. At this time, the bacteria with the above-mentioned anti-tinea versicolor effect contain at least one selected from human Staphylococcus aureus strains, hemolytic Staphylococcus aureus strains and Staphylococcus vorus strains. It should be noted that the above-mentioned human Staphylococcus aureus strains are preferably human Staphylococcus aureus strains with anti-tinea versicolor effect. In addition, the above-mentioned hemolytic Staphylococcus aureus strains are preferably hemolytic Staphylococcus aureus strains with anti-tinea versicolor effect. In addition, the above-mentioned Staphylococcus vorus strains are preferably Staphylococcus vorus strains with anti-tinea versicolor effect. In addition, specific examples of Staphylococcus aureus strains, Staphylococcus hemolyticus strains, and Staphylococcus woertzi strains are as described above.

[0203] [Process (1)]

[0204] Step (1) is a step of collecting bacterial flora from at least one of the ankle and sole of a person (preferably a healthy person without tinea tinea symptoms) and culturing the bacterial flora. The bacterial flora is collected from the ankle and / or sole of the person using a swab or the like, and smeared on a culture medium for culturing. Thus, each strain forms a colony.

[0205] [Step (2)]

[0206] Step (2) is a step of isolating and culturing the bacterial flora cultured in step (1) to obtain candidate bacteria. The colonies formed by the culture in step (1) are collected separately using a platinum loop or the like, and smeared on a culture medium for isolation and culture. In this way, a large number of bacteria contained in the bacterial flora contained in the ankles and / or soles of the feet of a person can be isolated. It should be noted that the various bacteria cultured are candidate bacteria, and are preferably suspended in a bacterial stock solution and stored at a low temperature (e.g., -100 to -50°C, preferably -90 to -70°C) as a skin bacteria library.

[0207] [Step (3)]

[0208] Step (3) is a step of evaluating the anti-Trichophyton activity of the candidate bacteria obtained in step (2) to identify bacteria having an anti-Trichophyton activity.

[0209] In step (3), first, which candidate bacteria isolated from human ankles and / or soles have an anti-Trichophyton activity is evaluated. In this case, the anti-Trichophyton activity of the candidate bacteria is evaluated by the method described in "4. Evaluation of anti-Trichophyton activity" of the Examples.

[0210] Next, select bacteria with anti-Trichophyton effect and identify the bacteria. As the identification method, there is no particular limitation, and the method of comparing 16s rDNA sequences, the method of making a phylogenetic tree, etc. can be listed. For example, in the method of comparing 16srDNA sequences, the 16s rDNA sequence of the target bacteria can be analyzed, and the DNA sequence data can be used to perform BLAST search of NCBI to identify the bacteria. In addition, in the method of making a phylogenetic tree, the 16s rDNA sequence of the bacteria can be analyzed, and the 16s rDNA sequence data of the known bacteria can be merged for analysis to make a phylogenetic tree, and the target bacteria can be identified by the phylogenetic tree. It should be noted that in step (3), when the target bacteria are identified as Staphylococcus aureus strains, hemolytic Staphylococcus aureus strains or Staphylococcus vorus strains, the steps of calculating the identity of the 16s rDNA sequence of the target bacteria with sequence numbers 1, 10, 17, etc., the steps of confirming the DNA sequence identity of the target bacteria, etc.

[0211] The bacteria having an anti-trichophyte activity determined in step (3) may contain at least one selected from the group consisting of a human Staphylococcus strain having an anti-trichophyte activity, a hemolytic Staphylococcus strain having an anti-trichophyte activity, and a Staphylococcus vortex strain having an anti-trichophyte activity. Therefore, by taking out at least one selected from the group consisting of a human Staphylococcus strain having an anti-trichophyte activity, a hemolytic Staphylococcus strain having an anti-trichophyte activity, and a Staphylococcus vortex strain having an anti-trichophyte activity as the target from the stored skin bacteria library, a human Staphylococcus strain having an anti-trichophyte activity, a hemolytic Staphylococcus strain having an anti-trichophyte activity, and a Staphylococcus vortex strain having an anti-trichophyte activity can be obtained.

[0212] [Step (4)]

[0213] Step (4) is a step of preparing a composition for treating tinea versicolor containing bacteria having an anti-tinea versicolor activity. The bacteria having an anti-tinea versicolor activity determined in step (3) are appropriately cultured, purified, freeze-dried, etc., to prepare a composition for treating tinea versicolor containing bacteria having an anti-tinea versicolor activity. It should be noted that the bacteria having an anti-tinea versicolor activity contains at least one selected from the group consisting of Staphylococcus aureus strains, hemolytic Staphylococcus aureus strains and Staphylococcus vorusii strains, and preferably contains at least one selected from the group consisting of Staphylococcus aureus strains having an anti-tinea versicolor activity, hemolytic Staphylococcus aureus strains and Staphylococcus vorusii strains.

[0214] <Treatment Method>

[0215] According to one embodiment of the present invention, a method for treating tinea tinea is provided. In this case, the method comprises applying the composition for treating tinea tinea to the affected part. The composition for treating tinea tinea and its application method are as described above.

[0216] Example

[0217] Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited thereto.

[0218] 1. Collection of candidate bacteria

[0219] Bacterial flora was collected from the ankles and soles of five healthy people using swabs. The swabs with bacterial flora were streaked onto Anero Columbia RS blood agar medium and incubated at 35°C aerobically for one day. After incubation, representative colonies in terms of morphology, color, and dryness were collected using a platinum loop.

[0220] A platinum loop with the collected colonies attached was spread on Anero Columbia RS blood agar medium and cultured at 35°C under aerobic conditions for one day.

[0221] After the culture, the developed colonies were recovered with a platinum loop, suspended in a 25% glycerol bacterial stock solution and stored at -80°C. It should be noted that a total of 91 candidate bacteria were collected. At this time, 52 candidate bacteria were obtained from the ankles and 39 candidate bacteria were obtained from the soles.

[0222] 2. Preparation of known bacteria

[0223] As known bacteria, the following 32 strains of bacteria were prepared.

[0224] (1) Acinetobacter baumannii ATCC17978

[0225] (2) Corynebacterium glaucum JCM12208

[0226] (3) Corynebacterium jeikeium ATCC43734

[0227] (4) Corynebacterium striatum NBRC15291

[0228] (5) Enterococcus faecalis ATCC29212

[0229] (6) Escherichia coli ATCC25922

[0230] (7) Micrococcus luteus ATCC4698

[0231] (8) Moraxella atlantae NBRC14588

[0232] (9) Neisseria gonorrhoeae ATCC19424

[0233] (10) Pseudomonas aeruginosa ATCC27853

[0234] (11) Staphylococcus aureus ATCC29213

[0235] (12) Staphylococcus epidermidis ATCC12228

[0236] (13) Hemolytic Staphylococcus aureus ATCC29970

[0237] (14) Staphylococcus aureus ATCC27844

[0238] (15) Streptococcus agalactiae ATCC13813

[0239] (16) Streptococcus mitis JCM12971

[0240] (17) Streptococcus pyogenes ATCC12344

[0241] (18) Staphylococcus aureus ATCC12600

[0242] (19) Staphylococcus epidermidis ATCC14990

[0243] (20) Staphylococcus aureus ATCC27840

[0244] (21) Staphylococcus aureus ATCC35538

[0245] (22) Staphylococcus cohnii ATCC29974

[0246] (23) Hemolytic Staphylococcus ATCC700564

[0247] (24) Hemolytic Staphylococcus ATCC29969

[0248] (25) Staphylococcus aureus ATCC27845

[0249] (26) Staphylococcus aureus ATCC700236

[0250] (27) Staphylococcus krusei ATCC43959

[0251] (28) Staphylococcus lentus ATCC700403

[0252] (29) Staphylococcus lugdunensis ATCC49576

[0253] (30) Staphylococcus lugdunensis ATCC43809

[0254] (31) Staphylococcus vorticella ATCC27836

[0255] (32) Staphylococcus saprophyticus ATCC15305

[0256] 3. Preparation of evaluation culture medium

[0257] In order to evaluate the anti-Trichophyton activities of candidate bacteria and known bacteria, a fungal mixed dilution medium containing Trichophyton was prepared as an evaluation medium.

[0258] Specifically, one bead of Trichophyton rubrum ATCC28188 stored in Microbank was taken, smeared on a potato dextrose agar (PDA) slant agar medium, and statically cultured at 30°C under aerobic conditions.

[0259] After the culture, a fungal inoculum solution was prepared by adding phosphate buffered saline (PBS) supplemented with 0.05% polysorbate 80 to the PDA slant agar medium.

[0260] PDA was dissolved in ultrapure water to a concentration of 39.0 g / L, and the resulting solution was heated in an autoclave (121°C, 20 minutes). After air cooling, the fungal inoculum was mixed and diluted with the PDA solution and dispensed into a culture dish to solidify, thereby preparing a fungal mixed dilution culture medium.

[0261] 4. Evaluation of anti-Trichophyton activity

[0262] The anti-tinea vitiligo effects of the candidate bacteria (91 strains) and known bacteria (32 strains) were evaluated using a fungal mixed dilution medium as an evaluation medium.

[0263] Specifically, one bead containing a candidate bacterium or a known bacterium stored in a Microbank is taken, smeared on Anero Columbia RS blood agar medium, and statically cultured at 35° C. under aerobic conditions for 1 to 2 days, and the resulting bacteria are collected with a platinum loop.

[0264] The platinum loop with the collected bacteria attached was streaked onto the fungal mixed dilution medium and cultured statically at 30°C under aerobic conditions until turbidity in the agar medium caused by the proliferation of Trichophyton can be visually confirmed. After the culture, the proliferation inhibition zone formed in the fungal mixed dilution medium was observed, and the anti-Trichophyton effect of the candidate bacteria or known bacteria was evaluated according to the following criteria based on the size of the proliferation inhibition zone. It should be noted that typical examples of each evaluation are shown in Figure 1 middle.

[0265] ++: Clear proliferation arrest regions observed

[0266] +: No clear growth inhibition zone was observed, but growth inhibition of Trichophyton was observed -: No growth inhibition of Trichophyton was observed

[0267] First, the results obtained for known bacteria (32 strains) are shown in Table 4 below.

[0268] [Table 4]

[0269]

[0270]

[0271] From the results in Table 4, it can be seen that among the known bacteria (32 strains), 9 strains were "++", 10 strains were "+", and 13 strains were "-".

[0272] In addition, among the candidate bacteria (91 strains), the results showed that 23 strains were "++", 32 strains were "+", and 36 strains were "-".

[0273] 5. Identification of Candidate Bacteria

[0274] In order to analyze the relationship between the anti-Trichophyton effect of candidate bacteria and the type of candidate bacteria, candidate bacteria were identified by comparing 16s rDNA sequences.

[0275] Specifically, according to the instruction manual of NucleoSpin Microbial DNA, total DNA was extracted and purified from candidate bacteria cultured in Anero Columbia RS blood agar medium, and the DNA concentration and purity were measured using NanoDrop, an ultra-micro spectrophotometer.

[0276] Next, according to the instructions of the Bacterial 16S rDNA PCR kit, the purified total DNA was used as a template, and the attached primers F1 (sequence number 19) and R2 (sequence number 20) were used to amplify the 16S rDNA sequence region by PCR. The amplified DNA fragment (about 1,500 bp) was purified using NucleoSpin gel and PCR cleaning kit, and the DNA concentration and purity were measured using NanoDrop, an ultra-micro spectrophotometer. The amplified DNA fragment size as the theoretical value was confirmed by agarose gel electrophoresis.

[0277] The amplified DNA fragment (16S rDNA template sample) was mixed with the primers (F1 (sequence number 19), F2 (sequence number 21) or R2 (sequence number 20)) attached to the Bacterial 16SrDNA PCR Kit, and the target sequence was subjected to Sanger sequencing analysis. After assembling the obtained sequencing sequence, the NCBI BLAST search was performed on the base sequence (about 1,240-1,280 bp) of the region sandwiched by the common sequence 1 (AGCTTGC) and the common sequence 2 (AAGCTGG) shared by the 16s rDNA of the genus Staphylococcus to identify the candidate bacterial species. At this time, the base sequence of the target region of 16s rDNA (about 1,240 to 1,280 bp) is a part of the amplified DNA fragment (about 1,500 bp), and contains the common sequence 1 (AGCTTGC) and the common sequence 2 (AAGCTGG). In addition, in the obtained sequencing sequences, when there was no consensus sequence 1 (AGCTTGC), it was replaced by the order of GGTTGG and TGCTTGC; when there was no consensus sequence 2 (AAGCTGG), it was replaced by the order of GAAGTTGG, AAGTCGG, GAAGTCGA, AAGTCAG, GAGCTGG, AAGGGGGG, AAGTCTGG, CAGTCAG and CCGCTGG, and the candidate bacterial species were identified by performing NCBI BLAST search on the base sequence of the region sandwiched by each consensus sequence (approximately 1,240 to 1,280 bp). It should be noted that when the obtained sequencing sequence does not contain any one or both of the consensus sequence 1 (AGCTTGC) or its alternative sequences (GGTTGG, TGCTTGC) and the consensus sequence 2 (AAGCTGG) or its alternative sequences (GAAGTTGG, AAGTCGG, GAAGTCGA, AAGTCAG, GAGCTGG, AAGGGGGG, AAGTCTCTGG, CAGTCAG, CCGCTGG), the strain of the candidate bacteria is identified by performing a BLAST search of NCBI with the full-length base sequence of the obtained sequence (amplified DNA fragment (about 1,500 bp)) as the target.

[0278] It should be noted that when identifying candidate bacterial species, species showing 99% or more identity with the top 10 sequences hit in the BLAST search were selected. Here, in the case where the top 10 selected species contain multiple results of the same genus but different species, identification by genus name was adopted (Staphylococcus species and Micrococcus species (Micrococcus sp.)). The case where no species that meets the conditions is identified is unknown.

[0279] The identified candidate bacteria and the results of the anti-Trichophyton activity are shown in Tables 5 and 6 below.

[0280]

[0281]

[0282] In Tables 5 and 6, the identified candidate bacteria are sorted by species, and the results obtained by analyzing the ratio of anti-Trichophyton activity shown by each species are shown in Figure 2 In. By Figure 2 As a result, 100% and 86% of Staphylococcus aureus and hemolytic Staphylococcus aureus respectively showed "++" results.

[0283] In addition, among the 92 candidate bacteria, the results of the anti-Trichophyton activity according to the isolation site of 52 candidate bacteria obtained from ankles and 39 candidate bacteria obtained from soles are shown in Table 7 below.

[0284] [Table 7]

[0285]

[0286] According to the results in Table 7, among the 52 strains from ankles, 33% were "++", 31% were "+", and 37% were "-", and among the 39 strains from soles, 15% were "++", 41% were "+", and 44% were "-". It can be seen that the proportion of strains showing "++" in ankles is about twice that in soles.

[0287] 6. Preparation of the Phylogenetic Tree of Staphylococcus

[0288] Referring to the paper by Ghebremedhin B et al. (J Clin Microbiol, 2008; 46: 1019-1025: Genetic classification and distinguishing of Staphylococcus species based on different partial gap, 16S rRNA, hsp60, rpoB, sodA, and tuf gene sequences), a phylogenetic tree targeting the 16S rDNA sequences of 27 species of Staphylococcus was prepared for 27 known strains of Staphylococcus (Table 8 below) and 45 strains of Staphylococcus identified among the candidate bacteria (the bacteria extracted from Tables 5 and 6 are shown in Table 9 below). The prepared phylogenetic tree is shown in Figure 3 It should be noted that the CLC sequence viewer (ver.8.0) was used to create the phylogenetic tree.

[0289] [Table 8]

[0290]

[0291]

[0292] [Table 9]

[0293]

[0294]

[0295] Will Figure 3 The phylogenetic tree of the candidate bacteria was compared with the anti-Trichophyton results, and was roughly divided into cluster 1, which mainly showed "-" results, cluster 2, which mainly showed "++" results, and cluster 3, which mainly showed "+" results. Among them, cluster 2 was composed of Staphylococcus hominis and Staphylococcus hemolyticus.

[0296] Therefore, a phylogenetic tree of 6 known strains of human Staphylococcus and hemolytic Staphylococcus (Table 10 below) and 15 strains of bacteria identified as human Staphylococcus or hemolytic Staphylococcus among the candidate bacteria (the bacteria extracted from Table 9 are shown in Table 11 below) was prepared. The prepared phylogenetic tree of human Staphylococcus and hemolytic Staphylococcus is shown in Figure 4 and Figure 5 middle.

[0297] [Table 10]

[0298] serial number Bacteria strain 1 Staphylococcus hominis ATCC27844 2 Staphylococcus hominis ATCC27845 3 Staphylococcus hominis ATCC700236 4 Staphylococcus hominis A9 5 Hemolytic Staphylococcus ATCC29970 6 Hemolytic Staphylococcus ATCC700564

[0299] [Table 11]

[0300] serial number Bacteria result 2 Staphylococcus hominis ++ 3 Staphylococcus hominis ++ 37 Staphylococcus hominis ++ 40 Staphylococcus hominis ++ 45 Staphylococcus hominis ++ 62 Staphylococcus hominis ++ 64 Staphylococcus hominis ++ 74 Staphylococcus hominis ++ 20 Hemolytic Staphylococcus ++ 22 Hemolytic Staphylococcus ++ 23 Hemolytic Staphylococcus ++ 24 Hemolytic Staphylococcus ++ 25 Hemolytic Staphylococcus ++ 33 Hemolytic Staphylococcus ++ 35 Hemolytic Staphylococcus +

[0301] 7.16s rDNA sequence

[0302] (1) 16S rDNA sequence of Staphylococcus aureus strains

[0303] The 16s rDNA sequence of Staphylococcus aureus ATCC27844, a well-known bacterium, was confirmed through the ATCC database, and the base sequence of the region sandwiched by consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG) was confirmed. As a result, the 16s rDNA sequence of Staphylococcus aureus ATCC27844 has the base sequence of sequence number 1 (Staphylococcus aureus ATCC27844 genome position: 716544-717811). It should be noted that since sequence number 1 contains consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG), the 5' end of the base sequence of sequence number 1 is consensus sequence 1 (AGCTTGC), and the 3' end is consensus sequence 2 (AAGCTGG).

[0304] In addition, for the 16s rDNA sequences of candidate bacteria No. 2, 3, 37, 40, 45, 62, 64 and 74 identified as Staphylococcus aureus strains, the base sequences of the regions sandwiched between the consensus sequence 1 (AGCTTGC) and the consensus sequence 2 (AAGCTGG) (about 1,240 to 1,280 bp) were confirmed by the same method as in the above-mentioned "5. Identification of candidate bacteria". As a result, the 16s rDNA sequences of candidate bacteria No. 3, 40, 45, 64 and 74 had the base sequence of sequence No. 5, the 16s rDNA sequence of candidate bacteria No. 2 had the base sequence of sequence No. 7, the 16s rDNA sequence of candidate bacteria No. 37 had the base sequence of sequence No. 8, and the 16s rDNA sequence of candidate bacteria No. 62 had the base sequence of sequence No. 9.

[0305] In addition, the 16s rDNA sequences of Staphylococcus aureus ATCC27845 and Staphylococcus aureus ATCC700236, which are known bacteria, were confirmed through the ATCC database, and the base sequences of the regions sandwiched by the consensus sequence 1 (AGCTTGC) and the consensus sequence 2 (AAGCTGG) were confirmed. In addition, the 16s rDNA sequence of Staphylococcus aureus A9 (ATCC entrustment number: PTA-125203) was confirmed through the PATRIC database, and the base sequences of the regions sandwiched by the consensus sequence 1 (AGCTTGC) and the consensus sequence 2 (AAGCTGG) were confirmed. As a result, the 16s rDNA sequence of Staphylococcus aureus ATCC27845 has the base sequence of sequence number 1 (Staphylococcus aureus ATCC27845 genome position: 761822-763089), and the 16s rDNA sequence of Staphylococcus aureus ATCC700236 and the 16s rDNA sequence of Staphylococcus aureus A9 (ATCC commissioning number: PTA-125203) have the base sequence of sequence number 5 (Staphylococcus aureus ATCC700236 genome position: 849942-851209, Staphylococcus aureus A9 genome position: 185-1452).

[0306] (2) 16S rDNA sequence of hemolytic Staphylococcus aureus strains

[0307] The 16s rDNA sequence of Staphylococcus aureus ATCC29970, a well-known bacterium, was confirmed through the ATCC database, and the base sequence of the region sandwiched by consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG) was confirmed. As a result, the 16s rDNA sequence of Staphylococcus aureus ATCC29970 had the base sequence of sequence number 10 (Staphylococcus aureus ATCC29970 genome position: 807302-808569).

[0308] In addition, for the 16s rDNA sequences of candidate bacteria No. 22 to 25, 33 and 35 identified as hemolytic Staphylococcus aureus strains, the base sequences of the regions sandwiched between the consensus sequence 1 (AGCTTGC) and the consensus sequence 2 (AAGCTGG) (about 1,240 to 1,280 bp) were confirmed by the same method as in the above-mentioned "5. Identification of candidate bacteria". As a result, the 16s rDNA sequences of candidate bacteria No. 22, 24, 25 and 33 had the base sequence of sequence No. 13, the 16s rDNA sequence of candidate bacteria No. 35 had the base sequence of sequence No. 14, and the 16s rDNA sequence of candidate bacteria No. 23 had the base sequence of sequence No. 16. The 16s rDNA sequence of No. 20 identified as a hemolytic Staphylococcus aureus strain had the consensus sequence 1 (AGCTTGC) but did not have the consensus sequence 2 (AAGCTGG). Since the 16s rDNA sequence of No. 20 has an alternative sequence (GAGCTGG) of consensus sequence 2, the base sequence (about 1,267 bp) of the region between consensus sequence 1 (AGCTTGC) and the alternative sequence (GAGCTGG) of consensus sequence 2 was confirmed. As a result, the 16s rDNA sequence of the candidate bacteria No. 20 has the base sequence of sequence No. 15.

[0309] In addition, the 16s rDNA sequence of Staphylococcus aureus ATCC700564, a well-known bacterium, was confirmed through the ATCC database, and the base sequence of the region sandwiched by consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG) was confirmed. As a result, the 16s rDNA sequence of Staphylococcus aureus ATCC700564 had the base sequence of sequence number 10 (Staphylococcus aureus ATCC700564 genome position: 214068-215335).

[0310] The results obtained in the above (1) and (2) are shown in Tables 12 and 13 below.

[0311] [Table 12]

[0312]

[0313]

[0314] *ND: No data [Table 13]

[0315]

[0316] It should be noted that in Table 13, sequence numbers 5 and 7 to 9 are based on sequence number 1, and sequence numbers 13 to 16 are based on sequence number 10. In addition, for example, "45G>A" recorded in sequence number 5 means that the G (guanine) at the 45th position of sequence number 1 is mutated to A (adenine). In addition, for example, "488delA" recorded in sequence number 7 means that the A (adenine) at the 488th position of sequence number 1 is deleted. In addition, for example, "1182_1183insA" recorded in sequence number 8 means that A (adenine) is inserted between positions 1182 and 1183 of sequence number 1.

[0317] (3) 16S rDNA sequence of Staphylococcus vorticella strain

[0318] The 16s rDNA sequence of Staphylococcus worderi ATCC27836, a well-known bacterium, was confirmed through the ATCC database, and the base sequence of the region sandwiched between the consensus sequence 1 (AGCTTGC) and the consensus sequence 2 (AAGCTGG) was confirmed. As a result, the 16s rDNA sequence of Staphylococcus worderi ATCC27836 had the base sequence of sequence number 17 (Staphylococcus worderi ATCC27836 genome position: 725369-726636).

[0319] From the results of 7(1) to (3) above, it can be seen that human Staphylococcus aureus having a 16s rDNA containing a base sequence of sequence number 1 or a base sequence having 95% or more identity with sequence number 1, hemolytic Staphylococcus aureus having a 16s rDNA containing a base sequence of sequence number 10 or a base sequence having 95% or more identity with sequence number 10, and Staphylococcus woertzii having a 16s rDNA containing a base sequence of sequence number 17 or a base sequence having 95% or more identity with sequence number 17 have anti-Trichophyton activity.

[0320] 8. Effects on other Trichophyton species

[0321] In the above 4 to 7, a fungal mixed dilution medium containing Trichophyton rubrum ATCC28188 was used as an evaluation medium (see the above "3. Preparation of evaluation medium"). Here, the effect on other Trichophyton (Trichophyton other than Trichophyton rubrum (T. rubrum) ATCC28188) was evaluated.

[0322] (1) Preparation of a mixed dilution culture medium containing other Trichophyton species

[0323] Five fungal mixed dilution media containing Trichophyton were prepared by the same method as in the above “3. Preparation of evaluation culture media” except that beads of Trichophyton rubrum ATCC22402, beads of Trichophyton mentagrophytes TIMM2789, beads of Trichophyton mentagrophytes ATCCMYA-4439, beads of Trichophyton tonsurans ATCC56186, or beads of Trichophyton tonsurans ATCC28942 were used instead of beads of Trichophyton rubrum ATCC28188.

[0324] (2) Evaluation of the anti-Trichophyton effect on other Trichophyton fungi

[0325] The anti-tinea fungal activity of Staphylococcus aureus ATCC27844, Staphylococcus aureus ATCC27845, Staphylococcus aureus ATCC29969, Staphylococcus aureus ATCC700564, and Staphylococcus worderi ATCC27836, which are known bacteria and have been evaluated for their anti-tinea fungal activity against Trichophyton rubrum ATCC28188, was evaluated using a mixed dilution culture medium containing the above five fungi.

[0326] The evaluation method was the same as in the above-mentioned "4. Evaluation of anti-Trichophyton activity". The obtained results are shown in Table 13 below together with the results of the anti-Trichophyton activity against Trichophyton rubrum ATCC28188.

[0327]

[0328] From the results in Table 14, it can be seen that the anti-Trichophyton activity was equivalent to that of Trichophyton rubrum ATCC28188 among the five other Trichophyton species.

Claims

1. A composition for treating tinea versicolor, comprising at least one selected from the group consisting of Staphylococcus aureus strains, Staphylococcus hemolyticus strains and Staphylococcus woertzii strains.

2. The composition for treating tinea versicolor according to claim 1, comprising a Staphylococcus aureus strain.

3. The composition for treating tinea versicolor according to claim 2, wherein the Staphylococcus aureus strain has a 16s rDNA comprising the base sequence of SEQ ID NO: 1 or a 16s rDNA comprising a base sequence having 95% or more identity with SEQ ID NO: 1, and has an anti-tinea versicolor effect.

4. The composition for treating tinea versicolor according to claim 2 or 3, wherein the human Staphylococcus aureus strain comprises at least one selected from the group consisting of human Staphylococcus aureus ATCC27844, human Staphylococcus aureus ATCC27845, human Staphylococcus aureus ATCC700236 and human Staphylococcus aureus A9 (ATCC entrustment number: PTA-125203). 5 . The composition for treating tinea versicolor according to claim 1 , comprising a hemolytic Staphylococcus aureus strain.

6. The composition for treating tinea versicolor according to claim 5, wherein the hemolytic Staphylococcus aureus strain has a 16s rDNA comprising the base sequence of SEQ ID NO: 10 or a 16s rDNA comprising a base sequence having 95% or more identity with SEQ ID NO: 10, and has an anti-tinea versicolor effect.

7. The composition for treating tinea versicolor according to claim 5 or 6, wherein the hemolytic Staphylococcus aureus strain contains at least one selected from the group consisting of Staphylococcus aureus ATCC29970, Staphylococcus aureus ATCC700564 and Staphylococcus aureus ATCC29969. 8 . The composition for treating tinea versicolor according to claim 1 , comprising a Staphylococcus woermannii strain.

9. The composition for treating tinea versicolor according to claim 8, wherein the Staphylococcus woersii strain has a 16s rDNA comprising the base sequence of SEQ ID NO: 17 or a 16s rDNA comprising a base sequence having 95% or more identity with SEQ ID NO: 17, and has an anti-tinea versicolor effect.

10. The composition for treating tinea versicolor according to claim 8 or 9, wherein the Staphylococcus woersii strain contains Staphylococcus woersii ATCC27836.

11. The composition for treating tinea tinea according to any one of claims 1 to 10, wherein the pathogenic bacteria of tinea tinea comprises a fungus of the genus Trichophyton.

12. The composition for treating tinea versicolor according to claim 11, wherein the pathogenic bacteria of tinea versicolor comprises at least one selected from the group consisting of a fungal strain of Trichophyton rubrum, a fungal strain of Trichophyton mentagrophytes, and a fungal strain of Trichophyton tonsurans.

13. The composition for treating tinea vitiligo according to any one of claims 1 to 12, which is an external preparation.

14. A method for producing a composition for treating tinea tinea, comprising: A step (1) of collecting bacterial flora from at least one of a person's ankle and sole and culturing the bacterial flora, The step (2) of isolating and culturing the cultured bacterial flora to obtain candidate bacteria, step (3) of evaluating the anti-Trichophyton activity of the candidate bacteria to identify bacteria having anti-Trichophyton activity, and Step (4) of preparing a composition for treating tinea versicolor containing the bacteria having anti-tinea versicolor activity; The bacteria having the anti-Trichophyton activity contain at least one selected from the group consisting of Staphylococcus aureus strains, hemolytic Staphylococcus aureus strains and Staphylococcus woertzi strains.

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