Pharmaceutical composition for preventing or treating alopecia comprising ackermania

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating alopecia, comprising, as an active ingredient, an Ackermansia strain, a vesicle of the strain, a proteome and metabolome of the strain, a culture of the strain, a lysate of the strain, an extract of the strain, an extract of the culture, or an extract of the lysate. A food composition and a cosmetic composition. According to the present invention, it is possible to provide a pharmaceutical composition for preventing or treating alopecia, which has no side effects and has excellent effects of preventing alopecia and promoting hair nourishing.

Description

Technical Field

[0001] The present invention relates to a pharmaceutical combination for preventing or treating hair loss, and more particularly, to a pharmaceutical composition for preventing or treating hair loss comprising bacteria of the genus Akkermansia as an effective ingredient, a food composition for preventing or improving hair loss or for promoting hair growth, and a cosmetic composition. Background Art

[0002] With the progress of modern society, the number of patients suffering from hair loss has increased dramatically, and the age of patients suffering from hair loss has become younger and younger. Among people in their twenties and thirties, the number of patients suffering from hair loss has increased sharply.

[0003] It is reported that as hair loss worsens, psychological symptoms of depression or tension become increasingly prominent, sensitivity to stress also becomes increasingly severe, it is difficult to adapt to interpersonal relationships or relationships with the opposite sex, and it also brings flaws to family life, becoming a major concern in health care.

[0004] The cause of hair loss is still unknown, but possible causes reported include genetic factors, hormonal abnormalities, and immunological abnormalities.

[0005] Androgenic alopecia (AGA) is hair loss caused by the action of androgens on androgen-sensitive hair follicles, which results in vellus hair. It is speculated that this is largely related to genetic factors. Estrogenic alopecia is believed to be caused by a decrease in the amount of estrogen relative to androgen in the bloodstream. Most cases occur after menopause, and estrogenic alopecia can be improved through hormone replacement therapy, but it is still a difficult disease in most cases.

[0006] Drugs that can be used in the treatment of androgenic alopecia include androgen activity inhibitors such as minoxidil and finasteride, female hormones such as estrogen, estradiol, and progesterone, ketoconazole as an antifungal agent, pentadecane, cytopurine (6-benzylaminopurine), tertiary flavanone, adenosine, and the like.

[0007] However, minoxidil has side effects such as drug-induced hair loss, excessive hair growth, lowered blood pressure, and decreased heart rate, and has the problem of recurrence immediately after stopping use. On the other hand, finasteride has side effects such as prostate hyperplasia, erectile dysfunction, and ejaculation disorders, and has the side effect of worsening symptoms after stopping use. In addition, if women use minoxidil in high doses, it will cause hirsutism or the risk of giving birth to deformed babies. Finasteride has the risk of giving birth to deformed babies, so women, especially pregnant women, are prohibited from taking it.

[0008] In addition, there are many products that contain ingredients that promote blood circulation, strengthen hair root function, moisturize the scalp, remove dandruff, have anti-oxidation effects, and extend the hair growth period as active ingredients. However, these existing preparations have not yet proven to have outstanding therapeutic effects in terms of effects, and instead have raised the problem of side effects.

[0009] On the other hand, as an effort to use microorganisms to obtain anti-hair loss effects, Korean Patent No. 1600012 discloses a hair loss treatment agent that uses microorganisms such as Lactobacillus plantarum to ferment wild rice stem and malt, and then adds raw materials such as Houttuynia cordata and Polygonum multiflorum to it. Korean Patent Publication No. 2022-0021144 discloses a pharmaceutical composition for treating prostatic hyperplasia or alopecia that contains lactic acid bacteria of the genus Enterococcus as an active ingredient. However, these compositions have not yet shown significant hair loss treatment effects. Summary of the invention

[0010] Technical issues

[0011] The present invention is proposed to solve the above-mentioned problems. The purpose of the present invention is to provide a pharmaceutical composition for preventing or treating hair loss, which has excellent anti-hair loss, hair growth or hair growth promoting effects while being safe to the human body and having no side effects.

[0012] Another object of the present invention is to provide a food composition for preventing or improving alopecia, comprising live Akkermansia bacteria, dead bacteria, or a mixture thereof as an effective ingredient.

[0013] Another object of the present invention is to provide a cosmetic composition that can prevent, alleviate and improve hair loss or promote hair growth or hair production by preventing, alleviating and preventing scalp aging.

[0014] Technical Solution

[0015] In order to achieve the above-mentioned object of the present invention, the present invention provides a pharmaceutical composition for preventing or treating hair loss, comprising an Akkermansia strain, a vesicle of the strain, a proteome and a metabolome of the strain, a culture of the strain, a lysate of the strain, an extract of the strain, an extract of the culture or an extract of the lysate, and at least one pharmaceutically acceptable excipient as an active ingredient.

[0016] The Akkermansia strain may be Akkermansia muciniphila EB-AMDK19 (KCTC 13761BP) strain. The Akkermansia strain may be live bacteria, dead bacteria or a mixture thereof.

[0017] The pharmaceutical composition for preventing or treating hair loss of the present invention can be used to treat one or more hair loss diseases selected from the group consisting of androgenetic alopecia, telogen effluvium, alopecia areata, alopecia totalis, hypotrichosis, hereditary hypotrichosis simplex, frontal fibrosing alopecia, cicatricial alopecia, lichen planopilaris, ring alopecia, scarring alopacia, nonscarring alopacia, chemotherapy induced alopecia and alopecia universalis.

[0018] In addition to the Akkermansia strain, the pharmaceutical composition for preventing or treating hair loss of the present invention may further comprise at least one hair loss therapeutic agent selected from the group consisting of finasteride, dutasteride, minoxidil, episteride, alfatradiol, tofacitinib and ruxolitinib.

[0019] Yet another embodiment of the present invention relates to a food composition for preventing or improving hair loss, comprising an Akkermansia strain, a vesicle of the strain, a proteome and a metabolome of the strain, a culture of the strain, a lysate of the strain, an extract of the strain, an extract of the culture or an extract of the lysate, and at least one physiologically acceptable excipient, diluent or carrier as an active ingredient.

[0020] Another embodiment of the present invention relates to a cosmetic composition for preventing hair loss or promoting hair growth, comprising an Akkermansia strain, a vesicle of the strain, a proteome and a metabolome of the strain, a culture of the strain, a lysate of the strain, an extract of the strain, an extract of the culture or an extract of the lysate, and at least one excipient, diluent or carrier that can be used in cosmetics as an active ingredient.

[0021] Effects of the Invention

[0022] Through various embodiments of the present invention, a pharmaceutical composition for preventing or treating hair loss having excellent effects of treating hair loss and promoting hair growth and having almost no side effects can be provided.

[0023] The pharmaceutical composition for preventing or treating hair loss of the present invention has the effect of preventing the phenomenon of hair falling out from the scalp or preventing the phenomenon of hair becoming sparse or thin.

[0024] The food composition of the present invention has the following effects: not only has the function of generating new hair or promoting the above-mentioned hair growth, but also has the function of promoting the delay from the growth phase to the regression phase of the hair cycle and making the existing hair grow healthily.

[0025] The cosmetic composition of the present invention comprising live Akkermansia bacteria, dead Akkermansia bacteria, inactivated Akkermansia bacteria or pasteurized Akkermansia bacteria can prevent, alleviate and prevent scalp aging, improve the anti-hair loss effect caused by the aging, and provide a significant effect of promoting hair growth or hair development. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The photographs show the hair regrowth over the number of days after the samples were applied when each sample was administered to a hair loss mouse model in the Examples of the present invention.

[0027] Figure 2a-2b The figure shows the results of hair length changes in each experimental group.

[0028] Figure 3a-3c This is a graph showing the results of measuring the body weight, liver and prostate tissue weights of each experimental group after the fifth week of the experiment.

[0029] Figure 4 After the fifth week of the experiment, pictures of the prostate glands of each experimental group were taken.

[0030] Figure 5a-Figure 5b After the fifth week of the experiment, the skin tissues collected from each experimental group were stained with hematoxylin-eosin and then observed under an optical microscope. Figure 5a ) and front ( Figure 5b )’s photos. DETAILED DESCRIPTION

[0031] In the process of describing the present invention, when it is judged that the detailed description of the well-known structure or function of the present invention may unnecessarily obscure the gist of the present invention, the detailed description will be omitted.

[0032] Throughout this specification and claims, unless otherwise specified, the terms include or comprise refer to including the stated item, step, or group of items and steps, but not excluding any other item, step, or group of items or steps.

[0033] The terms "treat...", "treatment" and the like as used herein refer to temporarily or permanently alleviating symptoms, eliminating the cause of symptoms, or preventing or delaying the manifestation of symptoms of a disease or condition.

[0034] The term "prevention" used in the present specification refers to all actions to suppress hair loss or delay the onset of hair loss by administering the pharmaceutical composition of the present invention.

[0035] The term "improvement" as used in the present specification refers to all actions that reduce parameters associated with an abnormal state, for example, reduce the extent of symptoms.

[0036] The term "pharmaceutically acceptable" as used herein refers to compositions within the scope of sound medicine that are suitable for use in contact with tissues of subjects (e.g., humans) with reasonable benefit / risk without excessive toxicity, irritation, allergic response, other problems or complications.

[0037] In this specification, "hair loss" refers to the phenomenon of hair falling off from the scalp, or the phenomenon of hair thinning or fineness. The hair loss in the present invention may include androgenic alopecia, telogen effluvium, anaplastic alopecia, drug-induced telogen effluvium, postpartum telogen effluvium, etc. In addition, it may also include all kinds of hair loss caused by a series of factors, such as the formation of vellus hair, the formation of monopiles in group hairs, and the atrophy of hair follicles, which are abnormal hair loss patterns.

[0038] In the present specification, "promoting hair growth" refers not only to the function of generating new hair or the function of promoting hair growth, but also to the function of promoting the delay from the growth phase to the regression phase and promoting the healthy growth of existing hair.

[0039] One embodiment of the present invention relates to a pharmaceutical composition for preventing or treating hair loss, comprising an Akkermansia strain, a vesicle of the strain, a proteome and a metabolome of the strain, a culture of the strain, a lysate of the strain, an extract of the strain, an extract of the culture or an extract of the lysate, and at least one pharmaceutically acceptable excipient as an active ingredient.

[0040] The above-mentioned Akkermansia strain can use a commonly known strain, for example, a muciniphilic Akkermansia strain can be used. An example of the Akkermansia strain of the present invention can be the muciniphilic Akkermansia EB-AMDK19 strain isolated and deposited by the present applicant. Specifically, preferably, the muciniphilic Akkermansia EB-AMDK19 strain deposited by the present applicant in the Korea Biotechnology Research Institute (KCTC) on December 5, 2018 with the deposit number of KCTC 13761BP is used.

[0041] The above-mentioned Akkermansia strain may be live, dormant, inactivated, or may be pasteurized, dead, or a mixture thereof. The above-mentioned term "dead" refers to a strain inactivated by heat treatment. In one example, the dead Akkermansia of the present invention may be prepared by heat treating the Akkermansia strain at a temperature of 50°C to 100°C, preferably at a temperature of 60°C to 95°C, and more preferably at a temperature of 70°C to 90°C for 5 minutes to 1 hour. However, it is not limited thereto. When the heat treatment temperature is increased, the heat treatment time may be shortened.

[0042] The pharmaceutical composition for preventing or treating hair loss of the present invention may contain live Akkermansia muciniphila, dead Akkermansia muciniphila, or a mixture thereof in an amount of about 1×10 2 CFU is about 1×10 15 CFU, preferably, can be about 1×10 4 CFU is about 1×10 12 CFU, more preferably, can be about 1×10 5 CFU is about 1×10 10 CFU, more preferably, can be about 1×10 6 CFU is about 1×10 9 If the dosage of the strain is less than the above range, it is difficult to achieve a sufficient effect of preventing hair loss and promoting hair growth, and if the dosage of the strain is greater than the above range, it is difficult to expect a further improved effect.

[0043] In the present invention, live Akkermansia bacteria, dead Akkermansia bacteria or mixtures thereof are substantially purified. Substantially purified live Akkermansia bacteria, dead Akkermansia bacteria or mixtures thereof may contain at least about 50% in a sample, preferably, at least about 60%, 70%, 80%, 90%, 95%, 99% or more.

[0044] The pharmaceutical composition of the present invention can be used to treat one or more hair loss diseases selected from androgenic alopecia, telogen effluvium, alopecia areata, alopecia totalis, hypotrichosis, hereditary simple hypotrichosis, frontal fibrosing alopecia, scarring alopecia, lichen planus pilaris, alopecia annularis, scarring alopecia, non-scarring alopecia, chemotherapy-induced alopecia or alopecia universalis.

[0045] The pharmaceutical composition of the present invention may further comprise at least one hair loss therapeutic agent selected from the group consisting of finasteride, dutasteride, minoxidil, aprelet, alfaestradiol, tofacitinib and ruxolitinib. The Akkermansia strain of the present invention may be administered simultaneously with the hair loss therapeutic agent as a preparation, or may be administered simultaneously or sequentially as a separate preparation. The pharmaceutical composition for preventing or treating hair loss of the present invention not only shows an excellent anti-hair loss effect when administered alone, but also reduces the side effects of the hair loss therapeutic agent and further activates the efficacy when administered in combination with a hair loss therapeutic agent such as minoxidil and finasteride, and has a more excellent therapeutic effect than administering the above-mentioned hair loss therapeutic agent alone.

[0046] In one embodiment of the present invention, the culture of the Akkermansia strain refers to a culture product of a part or all of the substances contained in the culture medium of the strain, including the culture medium or the culture solution, and a concentrate thereof. For example, it may refer to a metabolite, secretion, or lysate thereof as a result of the strain culture, and the strain itself may also be contained in the culture.

[0047] In one embodiment of the present invention, the lysate of the Akkermansia strain may be a product obtained by lysing the strain itself by chemical or physical force.

[0048] In one example of the present invention, the extract may refer to a product obtained by extracting the strain itself, the vesicles of the strain, the proteome and metabolome of the strain, the culture of the strain, the lysate of the strain, or a mixture thereof, and is a broad concept including all substances that can be processed or treated by other methods after extraction. Specifically, the extract may be an ethanol fraction or an ethanol precipitate.

[0049] The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier includes lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, it also includes diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc.

[0050] The pharmaceutical composition can be formulated into oral preparations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, parenteral preparations, injections, and preparations for topical administration according to conventional methods.

[0051] Solid oral preparations include tablets, pills, powders, granules, capsules, etc. The solid preparations may contain one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc., and lubricants such as magnesium stearate and talc. Oral liquid preparations include suspensions, internal solutions, emulsions, syrups, etc., and may contain diluents such as water and liquid paraffin, wetting agents, sweeteners, aromatics, preservatives, etc. Parenteral preparations include sterile aqueous solutions, non-aqueous solvents, suspensions, oils, and freeze-dried preparations. Non-aqueous solvents and suspensions contain propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.

[0052] Furthermore, the pharmaceutical composition can be administered to mammals including or excluding humans in various ways, for example, by oral, intravenous, intramuscular or subcutaneous injection.

[0053] The composition of the present invention can be administered topically. Topical administration refers to the direct application of the active ingredient or composition (skin external preparation composition, etc.) to the skin and / or hair. The topical composition of the present invention can be in the form of a solution, emulsion, wax, cream, ointment, liposome, spray, gel, foam, roller stick or any other dosage form commonly used in dermatology.

[0054] In the pharmaceutical composition of the present invention, the dosage of the active ingredient may vary according to the patient's state and weight, the extent of the disease, the form of the drug, the route of administration, and the period, and may be appropriately selected according to the circumstances. According to the patient's state, weight, sex, age, severity of the disease, and route of administration, the preferred dosage of the pharmaceutical composition of the present invention may range from 0.001 mg / kg to 10 g / kg per day, preferably from 0.001 mg / kg to 1 g / kg. It may be administered once a day or in several doses. However, in any aspect, the above dosage should not be interpreted as limiting the scope of the present invention.

[0055] Another embodiment of the present invention relates to a food composition for preventing or inhibiting hair loss and promoting hair growth. The food composition of the present invention comprises an Akkermansia strain, a vesicle of the strain, a proteome and a metabolome of the strain, a culture of the strain, a lysate of the strain, an extract of the strain, an extract of the culture or an extract of the lysate, and at least one physiologically acceptable excipient, diluent or carrier as an active ingredient. The Akkermansia strain may be live, dormant, inactivated, or may be pasteurized, dead, or a mixture thereof.

[0056] In the present invention, all strains of the genus Akkermansia can be used, for example, strains of Akkermansia muciniphila can be used. In the present invention, a specific example of the strain of the genus Akkermansia muciniphila is Akkermansia muciniphila EB-AMDK19 isolated and deposited by the present applicant.

[0057] The food composition of the present invention can be prepared into health functional foods such as functional drinks, health supplementary foods, and special nutritional supplement foods. The food can be in the form of beverages such as tea, juice, carbonated drinks, ion drinks, processed dairy products such as milk and yogurt, chewing gum, cakes, Korean cakes, bread, biscuits, noodles, and other foods, and health functional food preparations such as powders, tablets, and capsules.

[0058] The food composition of the present invention may further contain sweeteners, flavoring agents, physiologically active ingredients, minerals, and the like in addition to the active ingredients.

[0059] Sweeteners can be used in an amount that brings appropriate sweetness to food, and can be natural or synthetic. Natural sweeteners can be sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose, maltose, etc.

[0060] In order to make the taste or aroma better, flavoring agents can be used, and natural or synthetic ones can be used. It is better to use natural flavoring agents. In the case of using natural flavoring agents, in addition to the flavor, the purpose of strengthening nutrition can also be achieved at the same time. Natural flavoring agents can be flavoring agents obtained from apples, lemons, citrus, grapes, strawberries, peaches, etc., or can be flavoring agents obtained from green tea leaves, polygonatum, bamboo leaves, cinnamon, chrysanthemum leaves, jasmine, etc. Flavoring agents obtained from ginseng (red ginseng), bamboo shoots, aloe, ginkgo, etc. can also be used. Synthetic flavoring agents can use esters, alcohols, aldehydes, and terpenes.

[0061] As the physiologically active substance, catechins such as catechin, epicatechin, gallocatechin, and epigallocatechin, vitamins such as retinol, ascorbic acid, tocopherol, calciferol, thiamine, and riboflavin can be used.

[0062] As the minerals, calcium, magnesium, chromium, cobalt, copper, fluoride, germanium, iodine, iron, lithium, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, silicon, sodium, sulfur, vanadium, zinc and the like can be used.

[0063] And, in addition to the above-mentioned sweeteners etc., the food composition of the present invention can also include preservatives, emulsifiers, acidulants, thickeners etc. as required. The above-mentioned preservatives, emulsifiers etc. are well known in the technical field to which the present invention belongs, and can be used arbitrarily in the materials well known in the technical field to which the present invention belongs.

[0064] Another embodiment of the present invention may be a cosmetic composition, which may include the above-mentioned Akkermansia strain, preferably, may include the muciniphilic Akkermansia strain. The cosmetic composition of the present invention comprises the muciniphilic Akkermansia EB-AMDK19 strain (KCTC 13761BP), vesicles of the above-mentioned strain, the proteome and metabolome of the above-mentioned strain, the culture of the above-mentioned strain, the lysate of the above-mentioned strain, the extract of the above-mentioned strain, the extract of the above-mentioned culture or the extract of the lysate, and at least one excipient, diluent or carrier that can be used for cosmetics as an active ingredient. The above-mentioned Akkermansia strain may be live, dormant, inactivated, or may be pasteurized, dead bacteria or a mixture thereof.

[0065] The cosmetic composition of the present invention can be prepared into various forms according to the usual preparation method of cosmetics. Specifically, the cosmetic composition can be prepared into the form of hair growth liquid, hair cream, hair milk, shampoo, hair conditioner, hair conditioner, hair spray, hair wax, hair oil, powder, gel, hair mask, hair cream, eyebrow growth agent, eyelash growth agent, eyelash nutrition agent or ointment.

[0066] Furthermore, the cosmetic composition may contain common auxiliary agents such as stabilizers, solubilizers, vitamins, pigments, and fragrances commonly used in the field of cosmetic compositions, and may contain a carrier that can be used in cosmetics.

[0067] Carriers that can be used in cosmetics include, but are not limited to, pure water, oil, wax, fatty acid, fatty alcohol, fatty acid ester, surfactant, hygroscopic agent, tackifier, viscosity stabilizer, chelating agent, buffer, preservative, lower alcohol, etc., and may also contain diluent, anti-inflammatory agent, antibacterial agent, antifungal agent, vitamin, ultraviolet blocker, antibiotic, perfume, dye as needed.

[0068] Based on the above results, the composition for preventing or treating hair loss of the present invention not only has excellent efficacy in preventing or treating hair loss, but can also alleviate and improve hair loss accelerated by scalp aging by preventing, alleviating and preventing scalp aging.

[0069] Hereinafter, the present invention will be described in detail by way of examples, but the following examples are merely illustrative to help understand the entire content of the present invention, and the content of the present invention is not limited to the following examples.

[0070] Example

[0071] Example 1

[0072] 1.1. Bacterial strain samples

[0073] The live Akkermansia muciniphila EB-AMDK19 (KCTC 13761BP) used in this experiment was 1×10 8 The concentration of CFU / 100 μL PBS (25% glycerol, 0.05% cysteine / PBS) was prepared.

[0074] Animal experiments

[0075] Animal experiments were conducted in accordance with the Animal Use and Care Protocol of the Institutional Animal Care and Use Committee (IACUC). Seven-week-old male C57BL / 6 mice were purchased and acclimated for one week before being raised for 5 weeks. The breeding environment maintained a specified temperature (22°C) and relative humidity (40% to 60%), and the light and dark were adjusted in a 12-hour cycle. A normal diet (chow diet) was provided to all experimental groups.

[0076] 1.3. Sample administration and experimental group setting

[0077] As shown in Table 1 below, the mice were divided into 4 groups (8 mice / group), and each mouse was subcutaneously injected and orally administered with each drug five times a week for a total of five weeks. In order to prepare a hair loss model, 0.5 mg / day of testosterone was subcutaneously injected into mice in all experimental groups. The group induced with hair loss by administration of testosterone was used as a negative control group, and the positive control group was orally administered with 0.5 mg / kg / day of finasteride. PBS containing L-cysteine ​​and glycerol was orally administered as a solvent in the live and dead bacteria administration groups of the genus Akkermansia of the present invention.

[0078] [Table 1]

[0079]

[0080] Test Example 1: Photo confirmation experiment of hair growth in mice

[0081] For the mice in each experimental group, the extent of hair growth was observed by taking photos of the hair. Figure 1The photos show the hair growth and regrowth over the number of days the sample was applied to the hair loss-induced mice. From the left, the results are the negative control group (testosterone), the positive control group (T+finasteride), the group administered with live Akkermansia muciniphila (T+EB-AMDK19), and the group administered with dead Akkermansia muciniphila (T+EB-AMDK19 HI). Each group applied 100 μL daily for 5 weeks, and confirmed whether hair growth occurred in the hairless area on the back of the mouse.

[0082] pass Figure 1 It was confirmed that the skin color of the finasteride-treated group, which served as the positive control group, darkened from the third week of treatment, and the growth of hair shafts was as expected. As time passed, the range gradually expanded, and in the fifth week, almost all parts turned black.

[0083] In the negative control group (testosterone), until the fifth week when the observation was completed, the skin color remained pink and almost all parts were free of hair.

[0084] In mice to which the sample containing live Akkermansia muciniphila was applied, a dark blue skin color was observed on the tail side of the hair loss site one week after the application, indicating that the expected result of hair growth was achieved faster than in the case of the positive control group. As a result, hair growth was significantly observed in the lower half of the hair loss site from the third week of application.

[0085] On the other hand, in the case of mice to which the dead bacterial cell sample of Akkermansia muciniphila was applied, similar to the live bacteria administration group, a dark blue skin color was observed in the central part of the area where hair loss occurred one week after the application, and from the fourth week of the application, hair growth began to occur significantly in the lower part of the area where hair loss occurred.

[0086] Test Example 2: Hair growth length increasing effect

[0087] After the 5-week experiment, the hair length of each individual in each experimental group was measured and the average value was calculated. Figure 2a , Figure 2b The graph shows the results of a hair growth length increase experiment.

[0088] Reference Figure 2a-2b First, it can be seen that the hair length of the negative control group to which distilled water was applied did not undergo a sudden growth or other changes.

[0089] The hair lengths of the finasteride-administered group and the live Akkermansia-administered group (T-EB-AMDK19), which served as the positive control group (T+finasteride), were similar. In contrast, the hair length of the group administered with dead Akkermansia cells (T+EB-AMDK19HI) was relatively short.

[0090] Results, such as Figure 2a-2bAs shown, it was confirmed that the hair length significantly increased with the treatment of Akkermansia strains, regardless of whether the treated cells were live or dead bacteria, compared with the control group (Control).

[0091] Test Example 3: Measurement of body weight and tissue weight

[0092] After the 5-week experiment, the mice in each group were euthanized, and the liver and prostate tissues were removed and weighed. Figure 3a-3c Take a picture of the prostate and compare (refer to Figure 4 ).

[0093] There was no change in body weight among the groups of mice, nor was there a significant difference in liver or prostate weight. There was also no significant change in prostate size.

[0094] Test Example 4: Experiment on the measurement of histological changes of mouse hair follicles

[0095] In order to confirm the morphological changes of hair follicles in male C57BL / 6 mice, the skin tissues collected in the fifth week of transdermal administration were stained with hematoxylin and eosin and the number of hair follicles was observed under a microscope. Figure 5a and Figure 5b shown.

[0096] Results of measuring the number of telogen hair follicles following sample treatment in C57BL / 6 mice induced with alopecia, as shown in Figure 5a-Figure 5b As shown, in the case of finasteride treatment, it was confirmed that the number of hair follicles in the telogen phase increased compared to the negative control group.

[0097] In contrast, when the Akkermansia strain (live bacteria) of the present invention was administered, it was confirmed that the number of hair follicles in the telogen phase increased significantly compared to the negative control group. In particular, when the Akkermansia strain (dead bacteria) of the present invention was administered, it was confirmed that the number of hair follicles in the telogen phase increased significantly.

[0098] The above description is only an example of the technical concept of the present invention. A person skilled in the art of the present invention may make various modifications and variations without departing from the essential characteristics of the present invention. The true protection scope of the present invention shall be interpreted by the protection scope of the invention claims, and all technical concepts within the same scope shall be interpreted as included in the scope of the present invention.

[0099] [Accession number]

[0100] Name of depository institution: Korea Life Engineering Research Institute

[0101] Accession number: KCTC 13761BP

[0102] Date of preservation: December 5, 2018.

[0103]

Claims

1. A pharmaceutical composition for preventing or treating hair loss, characterized in that: The invention comprises an Akkermansia strain, a vesicle of the strain, a proteome and a metabolome of the strain, a culture of the strain, a lysate of the strain, an extract of the strain, an extract of the culture or an extract of the lysate, and at least one pharmaceutically acceptable excipient as active ingredients.

2. The pharmaceutical composition for preventing or treating hair loss according to claim 1, characterized in that The above-mentioned Akkermansia strain is an Akkermansia muciniphila strain.

3. The pharmaceutical composition for preventing or treating hair loss according to claim 2, characterized in that: The Akkermansia muciniphila strain is the Akkermansia muciniphila EB-AMDK19 strain deposited under the deposit number KCTC 13761BP.

4. The pharmaceutical composition for preventing or treating hair loss according to claim 1, characterized in that: The Akkermansia strains are live, dormant, inactivated, pasteurized, dead or a mixture thereof.

5. The pharmaceutical composition for preventing or treating hair loss according to claim 1, characterized in that: The composition is used to treat one or more hair loss diseases selected from the group consisting of androgenic alopecia, telogen effluvium, alopecia areata, alopecia totalis, hypotrichosis, hereditary simple hypotrichosis, frontal fibrosing alopecia, scarring alopecia, lichen planus pubis, alopecia annulare, scarring alopecia, non-scarring alopecia, chemotherapy-induced alopecia and alopecia universalis.

6. The pharmaceutical composition for preventing or treating hair loss according to claim 1, characterized in that: The composition further comprises at least one hair loss therapeutic agent selected from the group consisting of finasteride, dutasteride, minoxidil, aprepitant, alfaestradiol, tofacitinib and ruxolitinib.

7. A food composition for preventing or improving hair loss, characterized in that: The invention comprises an Akkermansia strain, a vesicle of the strain, a proteome and a metabolome of the strain, a culture of the strain, a lysate of the strain, an extract of the strain, an extract of the culture or an extract of the lysate, and at least one physiologically acceptable excipient, diluent or carrier as an active ingredient.

8. The food composition for preventing or improving hair loss according to claim 7, characterized in that: The above-mentioned Akkermansia strain is an Akkermansia muciniphila strain.

9. The food composition for preventing or improving hair loss according to claim 8, characterized in that: The Akkermansia muciniphila strain is Akkermansia muciniphila EB-AMDK19 deposited under the deposit number KCTC 13761BP.

10. The food composition for preventing or improving hair loss according to claim 7, characterized in that: The above food composition comprises 1×10 4 CFU / ml to 1×10 12 CFU / ml of Akkermansia strains.

11. A cosmetic composition for preventing hair loss or promoting hair growth, characterized in that: The invention comprises an Akkermansia strain, a vesicle of the strain, a proteome and a metabolome of the strain, a culture of the strain, a lysate of the strain, an extract of the strain, an extract of the culture or an extract of the lysate, and at least one excipient, diluent or carrier that can be used in cosmetics as an active ingredient.

12. The cosmetic composition for preventing hair loss or promoting hair growth according to claim 11, characterized in that: The above-mentioned Akkermansia strain is an Akkermansia muciniphila strain.

13. The cosmetic composition for preventing hair loss or promoting hair growth according to claim 12, characterized in that: The Akkermansia muciniphila strain is the Akkermansia muciniphila EB-AMDK19 strain deposited under the deposit number KCTC 13761BP.

14. The cosmetic composition for preventing hair loss or promoting hair growth according to claim 11, characterized in that: The dosage form of the above composition is hair growth liquid, hair cream, hair milk, shampoo, hair conditioner, hair conditioner, hair spray, hair wax, hair oil, powder, gel, hair mask, hair cream, eyebrow growth agent, eyelash growth agent, eyelash nutrition agent or ointment.

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