Composition for relieving hair loss and promoting hair growth containing heat-treated lactic acid bacterium Lactobacillus fermentum LM1020

Abstract

The present application relates to heat-treated Lactobacillus fermentum LM1020 having an anti-hair loss and hair growth promoting effect, and more particularly, to heat-treated Lactobacillus fermentum LM1020 having an anti-hair loss and hair growth promoting effect by promoting the proliferation of dermal papilla cells of hair follicles and a composition containing the same. The heat-treated Lactobacillus fermentum LM1020 of the present application and the composition containing the same promote the proliferation of dermal papilla cells, are excellent in the inhibitory activity of 5α-reductase-1, and have an anti-hair loss and hair growth promoting effect by promoting the expression of FGF7, FGF10, and EGF, which are a kind of growth factors.

Description

[Technical Field]

[0001] The present application relates to heat-treated lactic acid bacteria, Rimosilactobacillus fermentum LM1020, which has the effects of preventing hair loss and promoting hair growth, and more specifically to heat-treated lactic acid bacteria, Rimosilactobacillus fermentum LM1020, which has the effects of preventing hair loss and promoting hair growth by promoting the proliferation of hair papilla cells in hair follicles, and a composition containing the same. [Background technology]

[0002] Hair loss refers to the absence of hair in areas where hair normally exists, and generally refers to the loss of mature hair from the scalp. In the past, hair loss was considered to be something that only men experienced, but in modern society, the number of women suffering from hair loss is increasing, and the age at which hair loss occurs is gradually becoming younger. As the number of hair loss patients increases, research into the causes, treatments, and treatments for hair loss is gaining attention.

[0003] Currently, the most effective medications for preventing or treating hair loss are minoxidil and Propecia. However, minoxidil also affects hair growth throughout the body, causing it to grow thicker and darker. Because minoxidil lowers blood pressure, it should be avoided by people with low blood pressure. Because the drug is metabolized in the liver, it should also be avoided by people with liver problems. Furthermore, because Propecia is an androgen, it is prohibited for women to take it. It is known to cause side effects such as loss of libido and sexual dysfunction. Recently, a warning was added to the drug after reports of depression and low mood among patients who have taken it. Therefore, there is a need to develop a hair loss treatment with fewer side effects than minoxidil and Propecia, yet with superior effectiveness.

[0004] On the one hand, microbial resources are classified as sustainable resources in that they can be reproduced, unlike oil, water, etc. Since they utilize the unique characteristics of microorganisms adapted to diverse environments, they have a very high potential for research and industrial applications. In particular, components derived from strains that can provide health benefits, although inactivated by heat treatment or the like, are called postbiotics. Postbiotics have functions such as immunomodulation, improvement of skin condition, antioxidant activity, and inflammation regulation. Because they are inactivated, they have advantages over probiotics in terms of stability, safety, economy, storability, etc.

[0005] The surface of the skin and the openings of hair follicles are sites where microbial communities are abundant and strong immune activation is observed. There is a strong correlation between the immune privilege essential for the hair cycle and the microbial community. Changes in the microbiome or absorption of microbial metabolites in hair follicles are related to the inflammatory response of hair follicles, such as the regulation of skin immune responses and homeostasis. If the inflammation of hair follicles is alleviated, the possibility of hair regrowth increases. Therefore, the management of the microbiome at the local scalp site is very important for hair loss and hair growth.

[0006] Therefore, products for preventing hair loss, promoting hair growth / hair regrowth, and hair growth / growth, aimed at applying microorganisms to the recently increasing number of hair loss patients, have been developed. As an example, there is Korean Patent Publication No. 10-2017-0038462, etc. However, research on the exact mechanism of hair growth regulation by dermal papilla cells and new regulatory substances is still insufficient.

[0007] Therefore, the present inventors studied a composition for preventing hair loss or promoting hair growth that can promote the proliferation of dermal papilla cells (hDPCs, human Dermal Papilla Cells) of hair follicles, and as a result, confirmed that heat-treated Lactobacillus rhamnosus fermentum LM1020 (KCCM12918P) promotes the proliferation of dermal papilla cells of hair follicles, and completed the present invention.

Summary of the Invention

Problems to be Solved by the Invention

[0008] This application aims to provide a composition containing heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 (KCCM12918P) having an anti-hair loss and hair growth promoting effect.

[0009] However, the problems to be solved by this application are not limited to the above-mentioned problems, and other problems not mentioned should be clearly understood by those skilled in the art from the following description.

Means for Solving the Problems

[0010] The first aspect of this application provides a cosmetic composition for promoting dermal papilla cell proliferation, containing heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 (KCCM12918P) as an active ingredient.

[0011] The second aspect of this application provides a food composition for promoting dermal papilla cell proliferation, containing heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 (KCCM12918P) as an active ingredient.

[0012] The third aspect of this application provides a pharmaceutical composition for hair loss treatment, containing heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 (KCCM12918P) as an active ingredient.

Effects of the Invention

[0013] The heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 of this application and the composition containing the same promote the proliferation of dermal papilla cells, have excellent inhibitory activity against 5α-reductase-1, and promote the expression of FGF7, FGF10, and EGF, which are a kind of growth factors, thereby having an anti-hair loss and hair growth promoting effect.

Brief Description of the Drawings

[0014]

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Mode for Carrying Out the Invention

[0015] Hereinafter, with reference to the accompanying drawings, embodiments of the present application will be described in detail so that those having ordinary knowledge in the technical field to which the present application pertains can easily implement it. However, the present application can be embodied in various different forms and is not limited to the embodiments described herein. And in the drawings, in order to clearly explain the present application, parts not related to the explanation are omitted, and similar reference numerals are given to similar parts throughout the specification.

[0016] Throughout the specification of the present application, when a member is said to be "on" another member, this includes not only the case where a member is in contact with another member, but also the case where there are other members between the two members.

[0017] Throughout the specification of the present application, when a part "includes" a certain component, this means that, unless otherwise stated to the contrary, it does not exclude other components, but may further include other components. Terms such as "about" and "substantially" used throughout the specification of the present application are used to mean the numerical value or a meaning close to that numerical value when manufacturing and material tolerances inherent in the stated meaning are presented, and are used to prevent unscrupulous infringers from improperly using the disclosure in which exact or absolute numerical values are mentioned to assist in the understanding of the present application. The term "~(a) step" or "step of ~" used throughout the specification of the present application does not mean "step for ~".

[0018] Throughout the specification of the present application, the term "these combination(s)" included in the Markush-form expression means one or more mixtures or combinations selected from the group consisting of the components described in the Markush-form expression, and means including one or more selected from the group consisting of the above components.

[0019] Throughout the specification of the present application, the description "A and / or B" means "A or B, or A and B".

[0020] Hereinafter, embodiments and examples of the present application will be described in detail with reference to the attached drawings. However, the present application is not limited to such embodiments, examples, and drawings.

[0021] The first aspect of the present application provides a cosmetic composition for promoting the growth of dermal papilla cells, which contains heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 (KCCM12918P) as an active ingredient.

[0022] Throughout the specification of the present application, the term "heat-treated lactic acid bacterium" means dead cells obtained by heat-treating the Lactobacillus fermentum LM1020 strain to inactivate it.

[0023] Throughout the specification of the present application, the term "dead cells" is the opposite concept of live bacteria, and means a form in which live bacteria and metabolites obtained by fermentation are made unable to grow by heat treatment or the like. Dead cells may contain antibacterial active substances such as cytoplasm, cell wall, bacteriocin, polysaccharide, organic acid, etc. Products using the dead cells have higher stability compared to live bacteria products, are particularly excellent in heat resistance, and have high stability against the external environment, so they are easier to store than existing live bacteria products and have the advantage of being able to extend the distribution period. In addition, due to the strengthening of regulations on the use of antibiotics, their usability as an alternative and the fact that there are only a few companies that have really entered the production of dead cell products, the marketability and growth potential are very high.

[0024] In one embodiment of the present application, the component derived from the Limosilactobacillus fermentum LM1020 strain may be derived from fermented dough, but is not limited thereto.

[0025] In one embodiment of the present application, the heat-treated lactic acid bacterium Limosilactobacillus fermentum LM1020 may have a ratio of saturated fatty acid: unsaturated fatty acid: cyclic fatty acid of 0.1 to 2: 0.25 to 5: 0.03 to 0.6, and preferably may be 1: 2.5: 0.3, but is not limited thereto.

[0026] In one embodiment of the present application, the heat-treated lactic acid bacterium Limosilactobacillus fermentum LM1020 may increase the expression of CDK2, CDK4, cyclin B1, and cyclin D1.

[0027] In one embodiment of the present application, the heat-treated lactic acid bacterium Limosilactobacillus fermentum LM1020 may decrease the expression level of the 5α-reductase-1 gene and increase the expression levels of the FGF7, FGF10, and EGF genes.

[0028] In one embodiment of the present application, the cosmetic composition for promoting dermal papilla cell proliferation may further contain elmentol, salicylic acid, and dexpanthol.

[0029] In one embodiment of the present application, when the heat-treated lactic acid bacterium Limosilactobacillus fermentum LM1020 of the present application and the complex of elmentol, salicylic acid, and dexpanthol are treated together, the effect of promoting the growth of dermal papilla cells is more excellent than when the heat-treated lactic acid bacterium Limosilactobacillus fermentum LM1020 is used alone.

[0030] In one embodiment of the present application, the heat-treated lactic acid bacterium Limosilactobacillus fermentum LM1020 is 1×10 4 cell / mL~1×10 8It may be <number> cells / mL, preferably <number> cells / mL 6 ~<number> cells / mL 7 It may also be <number> cells / mL, more preferably <number> cells / mL 6 or <number> cells / mL, but it is not limited thereto. 7

[0031] In one embodiment of the present application, the cosmetic composition for promoting dermal papilla cell proliferation may further contain purified water, ethanol, Alanine / Histidine / Lysine Polypeptide Copper HCl, polyacrylate crosspolymer-6, coconut acid, proline, tea tree oil, glycerin, peptide, butylene glycol, 1,2-hexanediol, green tea extract, lavender flower extract, carline extract and ethylhexanediol, and the cosmetic composition for promoting dermal papilla cell proliferation may increase the microbial diversity and lactic acid bacteria diversity of the scalp.

[0032] The second aspect of the present application provides a food composition for promoting dermal papilla cell proliferation, which contains heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 (KCCM12918P) as an active ingredient. The contents overlapping with the first aspect of the present application are also commonly applicable to the food composition of the second aspect of the present application.

[0033] The term "food" used throughout the specification of the present application includes meats, sausages, breads, chocolates, candies, snacks, confectioneries, pizzas, ramen, other noodles, gums, dairy products including ice creams, various soups, beverages, teas, drink agents, alcoholic beverages, vitamin complexes, functional foods and health foods, etc., and includes all foods in the ordinary sense.

[0034] ​The term "health functional food" used throughout the specification of this application means a food manufactured and processed using raw materials and ingredients having functionality useful for the human body according to Law No. 6727 on health functional foods. "Functionality" means obtaining effects useful for health care purposes such as regulating nutrients with respect to the structure and function of the human body and physiological actions.

[0035] The food of this application can be manufactured by methods commonly used in the industry. During the said manufacturing, raw materials and ingredients commonly added in the industry may be added for manufacturing. Also, the dosage form of the said food may be manufactured without limitation as long as it is a dosage form recognized as a food. The food composition of the present invention may be manufactured in various forms of dosage forms. Since it uses food as a raw material, different from general drugs, it has the advantage of having no side effects that may occur during long-term use of drugs and is excellent in portability. Therefore, the food of the present invention can be ingested as an adjuvant for enhancing the effect of improving the intestinal environment.

[0036] The said "health food" means a food having a positive health maintenance and promotion effect compared to general food, and "health supplement food" means a food for health supplement purposes. In some cases, the terms health functional food, health food, and health supplement food may be used interchangeably. Specifically, the said health functional food is a food in which the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 of this application is added to food materials such as beverages, teas, spices, gums, confectioneries, etc., or manufactured into capsules, powders, suspensions, etc., and means that it brings specific health effects when ingested. Since it uses food as a raw material, different from general drugs, it has the advantage of having no side effects that may occur during long-term use of drugs.

[0037] Since the food composition of this application can be ingested daily, a high effect can be expected for the improvement of depression, and thus it can be used very usefully.

[0038] The food composition may further contain a physiologically acceptable carrier, but the type of the carrier is not particularly limited, and any carrier commonly used in the technical field can be used.

[0039] In addition, the food composition may contain additional ingredients commonly used in food compositions that can improve odor, taste, visual appearance, etc. For example, it may contain vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, pantothenic acid, etc. It may also contain minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), chromium (Cr), etc. It may also contain amino acids such as lysine, tryptophan, cysteine, valine, etc.

[0040] In addition, the food composition may contain food additives such as preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), bactericides (sun-dried powder and highly sun-dried powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), etc.), colorants (tar dyes, etc.), color developers (sodium nitrite, etc.), bleaching agents (sodium sulfite), seasonings (MSG sodium glutamate, etc.), sweeteners (dulcin, cyclamate, saccharin, sodium, etc.), flavors (vanillin, lactones, etc.), swelling agents (alum, potassium hydrogen D-tartrate, etc.), fortifiers, emulsifiers, thickeners (pastes), film-forming agents, gum bases, antifoaming agents, solvents, improvers, etc. The additives may be selected according to the type of food and used in appropriate amounts.

[0041] The heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 of the present application may be added as it is, or used together with other foods or food ingredients, and may be appropriately used by ordinary methods. The mixing amount of the active ingredient may be determined appropriately according to its purpose of use (prevention, health or therapeutic treatment). Generally, when manufacturing foods or beverages, the food composition of the present invention may be added in an amount of 50 parts by weight or less, specifically 20 parts by weight or less, based on the food or beverage. However, when ingested for a long time for the purpose of health and hygiene, it may contain a content below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

[0042] An example of the food composition of the present application may be used as a health beverage composition. In this case, various flavoring agents or natural carbohydrates may be contained as additional ingredients like ordinary beverages. The above-mentioned natural carbohydrates may be monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrin and cyclodextrin; sugar alcohols such as xylitol, sorbitol, and erythritol. Sweetening agents may use natural sweetening agents such as thaumatin and stevia extract; synthetic sweetening agents such as saccharin and aspartame. The proportion of the above-mentioned natural carbohydrates may generally be about 0.01 - 0.04 g, specifically about 0.02 - 0.03 g, per 100 mL of the health beverage composition of the present invention.

[0043] In addition to the above, the health beverage composition may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, or carbonating agents. Additionally, it may contain natural fruit juice, fruit juice beverages, or pulp for manufacturing vegetable beverages. Such components may be used independently or in combination. The proportion of such additives is not particularly important, but it is generally selected in the range of 0.01 - 0.1 parts by weight per 100 parts by weight of the health beverage composition of the present invention.

[0044] The food composition of the present application may contain the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 of the present application in various weight percentages as long as it can exhibit the effects of preventing hair loss and promoting hair growth. Specifically, the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 of the present application may be contained in an amount of 0.00001 to 100% by weight or 0.01 to 80% by weight based on the total weight of the food composition, but is not limited thereto.

[0045] In one embodiment of the present application, the food composition may be a health functional food composition.

[0046] The third aspect of the present application provides a pharmaceutical composition for treating hair loss, which contains the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 (KCCM12918P) as an active ingredient. The contents overlapping with the first aspect and the second aspect are also both applicable to the pharmaceutical composition of the third aspect of the present application.

[0047] In one embodiment of the present application, when formulating the pharmaceutical composition, it may be formulated and used in the form of an oral dosage form such as a powder, granule, tablet, capsule, suspension, emulsion, syrup, aerosol, etc., an external preparation, a suppository, or a sterile injection solution by a conventional method, but is not limited thereto.

[0048] In one embodiment of the present application, when formulating the pharmaceutical composition, it may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, or surfactants generally used, but is not limited thereto.

[0049] In one embodiment of the present application, solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. Such solid preparations may be prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, or gelatin, etc., with the components derived from the strain. Also, for example, in addition to simple excipients, lubricants such as magnesium stearate and talc may be used, but it is not limited thereto.

[0050] In one embodiment of the present application, liquid preparations for oral administration include suspensions, oral solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, such as wetting agents, sweeteners, flavoring agents, preservatives, etc., may be included, but it is not limited thereto.

[0051] In one embodiment of the present application, preparations for parenteral administration may include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories, but it is not limited thereto. For example, as the non-aqueous solvent or suspension, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, etc. may be used, but it is not limited thereto. For example, as the suppository, witepsol, macrogol, tween 61, cocoa butter, laurin fat, glycerogelatin, etc. may be used, but it is not limited thereto.

[0052] The pharmaceutical composition according to one embodiment of the present application may be a pharmaceutical composition or a quasi-drug composition.

[0053] As used throughout the specification of this application, the term "quasi-drug" means an article with a milder effect than a pharmaceutical among articles used for the purpose of diagnosing, treating, improving, alleviating, treating or preventing diseases in humans and animals. For example, according to the Pharmaceutical Affairs Law, quasi-drugs exclude articles used for pharmaceutical purposes, and include products used for treating or preventing diseases in humans and animals, products with a mild or non-direct effect on the human body, etc.

[0054] The quasi-drug composition of this application may be manufactured into a dosage form selected from the group consisting of body cleansers, disinfectant cleaners, detergents, kitchen detergents, cleaning detergents, toothpastes, gargles, wet tissues, laundry detergents, soaps, hand washes, hair shampoos, hair conditioners, humidifier fillers, masks, ointments, and filter fillers, but is not limited thereto.

[0055] In one embodiment of this application, the pharmaceutical composition may be administered in a pharmaceutically effective amount. As used in this application, the term "pharmaceutically effective amount" means an amount sufficient to treat or prevent a disease at a reasonable benefit / risk ratio applicable to medical treatment or prevention. The level of the effective dose may be determined by factors including the severity of the disease, the activity of the drug, the age, weight, health, gender of the patient, the drug sensitivity of the patient, the administration time of the composition of the present invention used, the administration route and excretion rate, the treatment period, elements including drugs formulated or used simultaneously with the composition of the present invention used, and other elements well known in the medical field. The pharmaceutical composition of this application may be administered alone or in combination with components known to have a therapeutic effect on known intestinal diseases. It is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects considering all of the above factors.

[0056] In one embodiment of the present application, the dosage of the pharmaceutical composition may be determined by those skilled in the art in consideration of the purpose of use, the severity of the disease, the age, weight, sex, medical history of the patient, or the type of substance used as the active ingredient. For example, the pharmaceutical composition of the present invention may be administered at about 0.1 ng to about 1,000 mg / kg, preferably 1 ng to about 100 mg / kg per adult. The dosing frequency of the composition of the present application is not particularly limited thereto, but may be administered once a day or the dose may be divided and administered several times. The dosage or dosing frequency does not limit the scope of the present application in any way.

[0057] The pharmaceutical composition of the present application is not particularly limited thereto, but depending on the purpose, it may be administered via routes such as intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, transdermal patch administration, oral administration, intranasal administration, pulmonary administration, rectal administration, etc. However, in the case of oral administration, it may be administered in a non-formulated form. Since the heat-treated lactic acid bacterium Limosilactobacillus fermentum LM1020 may be denatured or decomposed by gastric acid, the oral composition may be coated with the active drug or administered orally in a formulated form or an oral patch form so as to be protected from degradation in the stomach. In addition, the composition may be administered by any device capable of moving the active substance to the target cell.

[0058] Hereinafter, the present invention will be described in more detail with reference to the examples of the present application. However, the following examples are only illustrative for helping the understanding of the present application, and the content of the present application is not limited to the following examples.

Examples

[0059] Example 1. Comparison of the effect of heat-treated lactic acid bacteria on dermal papilla cell proliferation Dermal papilla cells were purchased from PromoCell and seeded at 5000 - 10000 cells / cm 2They were inoculated into the flask at a density of and then cultured. The dermal papilla cells were cultured in a dermal papilla cell culture medium prepared by adding growth factors (40 μL / mL fetal calf serum, 4 μL / mL bovine pituitary extract, 1 ng / mL fibroblast growth factor, 5 μg / mL insulin) to a commercial medium, basal media, and cultured at 37°C while maintaining a CO2 concentration of 5%. The dermal papilla cells were subcultured and used in experiments when they reached 80 - 90% confluency. The dermal papilla cells used in the study were stored in liquid nitrogen up to 2 - 5 passages and used up to a maximum of 10 passages in the experiments.

[0060] The effect of heat-treated lactic acid bacteria on promoting the proliferation of dermal papilla cells was confirmed by observing viable cells under a microscope through trypan blue staining. Dermal papilla cells that reached 80 - 90% confluency were inoculated into a 24-well plate at a density of 100,000 cells / well and cultured for 24 hours. Then, 7 heat-treated lactic acid bacteria at 1×10 cell / mL were treated, and the increased number of cells compared to the control group was confirmed by directly counting through a microscope. The heat-treated lactic acid bacteria used to compare the effect of promoting dermal papilla cell proliferation were Lactiplantibacillus plantarum LP1001, Lactococcus lactis LP1009, Lactiplantibacillus rhamnosus LP1011, Lactiplantibacillus paracasei LP1014, Bifidobacterium animalis subsp. lactis LP1017, Limosilactobacillus fermentum LP1016, Limosilactobacillus fermentum LM1020, Lactobacillus acidophilus LP1060, and Lactobacillus gasseri LP1065.

[0061] As a result of the comparison, none of the heat-treated lactic acid bacteria promoted the growth of dermal papilla cells. Among the nine types of heat-treated lactic acid bacteria, only Lactobacillus casei paracasei LP1014, Lactobacillus acidophilus LP1060, Lactobacillus fermentum LP1016, and Lactobacillus fermentum LM1020 were able to promote the growth of dermal papilla cells, and it was confirmed that the other heat-treated lactic acid bacteria rather inhibited the growth of dermal papilla cells (Figure 1).

[0062] Lactobacillus fermentum LP1016 and Lactobacillus fermentum LM1020 belong to the same genus and species, but LP1016 is derived from kimchi and LM1020 is derived from fermented dough, so there is a difference in the origin of each strain. As a result of the study, even when heat-treated by the same method, the heat-treated lactic acid bacteria Lactobacillus fermentum LP1016 derived from kimchi improved the growth of dermal papilla cells by 3.7%, while the heat-treated lactic acid bacteria Lactobacillus fermentum LM1020 derived from fermented dough showed a significant difference such as improving the growth of dermal papilla cells by 24.9%.

[0063] Example 2. Fatty acid composition of the cells of heat-treated lactic acid bacteria Bacterial fatty acids are precursors of intracellular membrane organelles including cell membranes and are known to play various roles within the bacteria. The internal standard substance (ISTD) was selected as methyl undecanoate, which is not generally present in nature. It was prepared at a concentration of 10,000 μg / mL using HPLC-grade n-hexane as the solvent and stored at -20°C. It was diluted as needed and used in the study. To extract the fatty acids of heat-treated lactic acid bacteria, 25 μL of the internal standard substance was added, and 200 μL of a chloroform and methanol 2:1 (v / v) mixed solution was added. Then, 300 μL of 0.6 M hydrochloric acid methanol solution was added for fatty acid derivatization, followed by homogenization for 120 seconds. After heating and reacting at 85°C for 60 minutes, it was allowed to cool to room temperature. 1 mL of n-hexane was added again, followed by homogenization for 120 seconds. After standing at room temperature for 60 - 120 minutes, the supernatant was used for analysis. The fatty acids were analyzed by gas chromatograph / mass spectrometer electron ionization analysis method. Helium was used as the mobile phase, and a DB-FastFAME column was used.

[0064] As a result, it was confirmed that the compositions of the bacterial fatty acids of heat-treated Lactiplantibacillus fermentum LP1016 and heat-treated Lactiplantibacillus fermentum LM1020, which are of the same genus and species but have different origins, are different from each other (Table 1). In particular, Linoleate was present only in heat-treated Lactiplantibacillus fermentum LM1020, and Behenic acid was present only in heat-treated Lactiplantibacillus fermentum LP1016. Among the fatty acids, Oleate was approximately 2.4 times more in heat-treated Lactiplantibacillus fermentum LM1020, and Lactobacillic acid was approximately 2.1 times more in heat-treated Lactiplantibacillus fermentum LP1016.

[0065] The ratios of saturated fatty acids to unsaturated fatty acids in the cells of both strains were also significantly different. For Lactobacillus fermentum LP1016 derived from kimchi, the ratio of saturated fatty acids:unsaturated fatty acids:cyclic fatty acids was 1:1:0.6, while for Lactobacillus fermentum LM1020 derived from fermented dough, it was 1:2.5:0.3, showing different compositions of each fatty acid and significant differences in the characteristics of the total fatty acids.

[0066]

Table 1

[0067] Example 3. Comparison of the effect of heat-treated lactic acid bacteria on promoting dermal papilla cell growth Through comparison with strains known to be effective in preventing hair loss, promoting hair growth, or promoting hair regrowth (Lactobacillus casei paracasei KCTC14004BP and Lactobacillus fermentum KCCM11910P), the effect of the heat-treated lactic acid bacteria Lactobacillus fermentum LM1020 on promoting the proliferation of dermal papilla cells was verified (Figure 2).

[0068] The strains used for comparison were all heat-treated at 121°C for 15 minutes to be inactivated.

[0069] After treating dermal papilla cells (10,000 cells / well) with heat-treated lactic acid bacteria at a concentration of 2.5×10 7 cell / mL, they were cultured as in Example 1, and the effect of promoting the growth of dermal papilla cells was calculated using the following formula.

[0070] The growth rate when only dermal papilla cells were cultured was compared with the growth rate when heat-treated lactic acid bacteria were added to confirm the effect of heat-treated lactic acid bacteria on promoting the growth of dermal papilla cells. The growth rate when dermal papilla cells were cultured by the above method without adding anything was calculated, and the growth rates of dermal papilla cells when heat-treated lactic acid bacteria Lactobacillus casei paracasei KCTC14004BP, heat-treated lactic acid bacteria Limosilactobacillus fermentum KCCM11910P, and heat-treated lactic acid bacteria Limosilactobacillus fermentum LM1020 were added. The effect of heat-treated lactic acid bacteria on promoting the growth of dermal papilla cells was determined by the following formula and compared. All tests were repeated 3 times, and the average of each result was calculated and compared.

[0071] Effect of promoting dermal papilla cell growth (%) = (B - A) ÷ A × 100 A = Growth rate of dermal papilla cells in the untreated group B = Growth rate of dermal papilla cells when treated with heat-treated lactic acid bacteria

[0072] As a result, at a concentration of 2.5×10 7 cell / mL, heat-treated lactic acid bacteria Limosilactobacillus fermentum KCCM11910P rather inhibited the growth of dermal papilla cells, and heat-treated lactic acid bacteria Lactobacillus casei paracasei KCTC14004BP promoted the growth of dermal papilla cells, but showed a cell growth rate more than 2 times lower than that of heat-treated lactic acid bacteria Limosilactobacillus fermentum LM1020 of the present invention.

[0073] Example 4. Proliferation effect of dermal papilla cells by different concentrations of heat-treated lactic acid bacteria Limosilactobacillus fermentum LM1020 It was confirmed whether the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020, which showed the most excellent growth-promoting effect on dermal papilla cells in Examples 1 and 2, could promote the proliferation of dermal papilla cells even in a situation where growth factors were insufficient. After inoculating dermal papilla cells in a 96-well plate and culturing them for 24 hours, the medium in the well was replaced with a medium lacking growth factor, and additional culture was performed for 24 hours. Then, heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 was added at different concentrations, and after 24 hours, it was confirmed whether the growth of dermal papilla cells was promoted. The growth-promoting effect of dermal papilla cells was confirmed by adding 0.5 mg / mL of thiazolyl Blue tetrazolium bromide (MTT), culturing at 37 °C, dissolving the generated formazan in DMSO, and then measuring the absorbance at 570 nm.

[0074] As a result, the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 was able to proliferate dermal papilla cells even under culture conditions lacking dermal papilla cell growth factors. In the concentration range of 1×10 3 cell / mL to 1×10 5 cell / mL, the growth of dermal papilla cells increased in a concentration-dependent manner. At high concentrations of 1×10 6 cell / mL or higher, the dermal papilla cell proliferation effect showed a similar tendency regardless of the concentration. The dermal papilla cell proliferation-promoting effect was most excellent at 1×10 7 cell / mL, and a 156% proliferation-promoting effect was confirmed compared to the untreated group (Figure 3).

[0075] Example 5. Increase in protein expression levels related to the proliferation of dermal papilla cells To confirm the mechanism of action by which the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020, which showed the most excellent dermal papilla cell growth-promoting effect in Examples 1 and 2, promotes the proliferation of dermal papilla cells, the protein expression levels related to the proliferation of dermal papilla cells were measured.

[0076] Dermal papilla cells are fibroblasts derived from the mesoderm, and the proliferation of dermal papilla cells is regulated by cell cycle proteins such as cyclins, CDKs (cyclin-dependent kinases), and CDK inhibitors. Cells exist in either a quiescent or proliferative state, and growing cells undergo the cell cycle of the G1 phase, the S phase which is the DNA synthesis phase, the G2 phase, and the M phase where mitosis occurs, and finally divide into two daughter cells to proliferate.

[0077] CDK2 (Cyclin-dependent kinase 2) is a kinase involved in cell cycle regulation and is essential for meiosis but not necessary for mitosis. It regulates the subsequent activation of cyclinB / CDK1 by phosphorylation to control the timing of entry into mitosis and meiosis as a mechanism for regulating the activation of cyclin BCDK1. The activity of CDK2 is maximally expressed in the S and G2 phases of cell division. CDK4 (Cyclin-dependent kinase 4) is required for the transition of the cell cycle from G1 to the S phase. CDK6 (Cyclin-dependent kinase 6) is involved in the initiation and maintenance of the cell cycle during cell differentiation while promoting the G1 / S transition. It mainly functions to prevent cell proliferation and regulate negative cell differentiation. Cyclin B1 is a regulatory protein involved in mitosis and is a cell cycle regulatory transcript expressed during the G2 / M stage of the cell cycle.

[0078] Cyclin B1 plays a role in determining that the cell undergoes mitosis. After being activated to form the cyclin B1-CDK1 complex, it promotes various mechanisms such as early mitosis.

[0079] Cyclin D1 is one of the target genes of the Wnt / β-catenin signaling pathway that plays an important role in processes such as hair growth, stem cell regulation, and cell proliferation, and affects cell division throughout the cell division cycle of dermal papilla cells.

[0080] Cyclin E1 may induce the early G1 phase of the cell division cycle in dermal papilla cells. Cyclin E1 promotes the transition from G1 to S phase and induces the initiation of DNA synthesis. Cyclin E1 is maximally expressed at the G1 / S stage of the cell cycle.

[0081] To measure the protein expression level of dermal papilla cells, dermal papilla cells were injected into a 6-well microplate at a concentration of 4×10 5 cells / mL and cultured for 24 hours. Then, the dermal papilla cell culture medium was replaced with a basal medium (a medium from which growth factors for dermal papilla cells such as insulin were removed), and the cells were cultured for an additional 24 hours. Thereafter, the dermal papilla cell culture medium was replaced with a medium treated with heat-killed Lactobacillus fermentum LM1020 at different concentrations (final concentrations: heat-killed Lactobacillus fermentum LM1020 1×10 6 , 1×10 7 and 1×10 8 cells / mL), and the growth of dermal papilla cells was induced while co-culturing the heat-killed Lactobacillus fermentum LM1020 at different concentrations with the dermal papilla cells for 24 hours. After the culture was completed, the proteins of the dermal papilla cells were extracted using Pro-Prep TM lysis buffer (Intron, Korea). The extracted proteins were measured for protein quantity using the BCA protein assay, and the protein expression level was measured by performing Western blotting with the Protein Simple Jess system (Jess; Protein Simple, USA). Using the capillary cartridge of Jess, electrophoresis, blocking, primary antibody reaction, and secondary antibody reaction were carried out inside the capillary, and the expression level was confirmed using the ECL detection reagent.

[0082] As a result, it was confirmed that heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 increased the expression of cyclin and CDK proteins, which are proteins necessary for the growth cycle of dermal papilla cells, and promoted the growth of dermal papilla cells (Figs. 4a to 4f). Although the degree of protein expression affecting the proliferation of dermal papilla cells differed depending on the treatment concentration of heat-treated lactic acid bacterium Lactobacillus fermentum LM1020, the expression of CDK2, CDK4, cyclin B1, and cyclin D1 increased, while the expression of CDK6 and cyclin E1 tended to decrease (Table 2).

[0083] In particular, heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 increased the expression level of cyclin B1 by up to 3.9-fold (Fig. 4d), which means that during the same growth time, more cells reached the G2 / M phase of the cell division cycle of dermal papilla cells than in the control group (untreated), and the number of dividing dermal papilla cells after DNA replication increased more.

[0084] Also, when heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 was treated, the expression of cyclin D1 protein, which affects cell division throughout the cell division cycle of dermal papilla cells, increased by up to 2.4-fold (Fig. 4e), which means that heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 formed a cyclin D1-CDK4 complex in dermal papilla cells and induced the conversion from the G1 phase to the S phase where DNA is replicated, promoting the growth of dermal papilla cells.

[0085] On the other hand, after treatment with heat-treated lactic acid bacterium Lactobacillus fermentum LM1020, the expression levels of cyclin E and CDK6, which induce the early G1 phase of the cell division cycle of dermal papilla cells, were slightly decreased or maintained at a level similar to that before treatment (Figs. 4c, 4f), which means that dermal papilla cells treated with heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 reached the G2 / M phase more after passing through the G1 phase, which is the initial stage of the cell division cycle.

[0086] [Table 2]

[0087] Example 6. Measurement of hair loss prevention and hair growth effects using human-derived tissue 6-1) Explant tissue culture Human scalp tissue, provided for research purposes (IRB No. 4-2021-1524; Bioethics Committee of Yonsei University College of Medicine and Severance Medical Center), was washed several times with PBS to remove residual impurities and then prepared into a 1 cm x 1 cm section.

[0088] Heat-treated lactic acid bacteria Limosilactobacillus fermentum LM1020 was added to a scalp tissue-specific medium at 1 × 10 8 cells / mL or 1 x 10 9 After diluting to a concentration of 1000 cells / mL, 50μL was applied to human scalp tissue. For the negative control group, 50μL of scalp tissue-specific medium was applied instead of the heat-treated Lactobacillus fermentum LM1020. The tissue was cultured in the specific medium at 37℃ and 5% CO2, with the specific medium replaced and the treatment applied every 24 hours. 72 hours after application, the subcutaneous tissue, epidermal tissue, and dermal tissue were separated from each tissue and used for the test.

[0089] 6-2) Real-Time Polymerase Chain Reaction (RT-PCR) The gene expression levels of hair loss and hair growth-related factors (5α-reductase-1, FGF7, FGF10, EGF) were confirmed using real-time polymerase chain reaction. The gene expression levels of 5α-reductase-1 were confirmed in subcutaneous tissue isolated from human scalp tissue, and the gene expression levels of FGF7, FGF10, and EGF were confirmed in epidermal and dermal tissue.

[0090] 5α-reductase-1, one of the hair loss-related factors, is mainly distributed in dermal papilla cells, sebaceous glands, keratinocytes of the epidermis and hair follicles, and is an enzyme that acts on Testosterone to produce DHT (Dihydrotestosterone), which is the main cause of hair loss. A decrease in the expression of the 5α-reductase-1 gene in human dermal papilla cells is known to be involved in preventing hair loss (H Rastegar et al., 2015).

[0091] FGF7 (fibroblast growth factor 7) is a growth factor produced by fibroblasts and secreted into keratinocytes, which promotes the proliferation of epithelial and epidermal cells. It is known to promote follicular cell differentiation, induce the proliferation of the vascular system of the dermal papilla, increase the amount of extracellular matrix, and maintain the hair follicles in the growth phase. FGF10 (fibroblast growth factor 10) is known as a factor that induces telogen hair follicles into the anagen or growth phase and contributes to the initial formation of cells, promoting hair growth (Sole Cho et al., 2016).

[0092] EGF is well known as a growth factor involved in the maturation of hair follicles and has been studied to promote the proliferation of dermal papilla cells through notch signaling activation (Zhang et al., 2016).

[0093] After the tested tissues were crushed using TissueLyser II (Qiagen), total RNA was extracted using TRIzol Reagent (Invitrogen). The extracted total RNA was used to synthesize cDNA using RNA to cDNA EcoDryTM Premix (Oligo dT) (Clontech). The synthesized cDNA, Taqman Fast Advanced Master Mix (Applied Biosystems), and Taqman primers for each target (SRD5A1 (5-α-reductase-1): Hs00971645_g1, FGF7: Hs00940253_m1, FGF10: Hs00610298_m1, EGF: Hs01100002_m1; Applied Biosystems) were used to perform real-time polymerase chain reaction. Relative quantitative analysis of each gene was performed using the housekeeping gene GAPDH (Hs02786624_g1, Applied Biosystems).

[0094] During cDNA amplification, the amplification amount was confirmed in real time, and the threshold cycle (Ct) value, which is the intersection of the amplification curve and the threshold line, was obtained. Based on this value, the relative quantification value (RQ) was calculated to confirm the relative mRNA expression level of the target gene. RQ was calculated using the following formula.

[0095] RQ = 2 -△△Cт △△Ct = △Ct(treatment) - △Ct(control) △Ct = Ct(target gene) - Ct(housekeeping gene) - Treatment (experimental group): Treated with the test product - Control (control group): Negative control group - Target gene: SRD5A1 (5α-reductase-1), FGF7, FGF10, EGF - Housekeeping gene: GAPDH

[0096] 6-3) Statistical analysis The statistical analysis was verified using the IBM SPSS statistics 25.0 program, and the significance between the experimental group and the control group was confirmed with a hypothesized mean difference of 5% (p < 0.05). After the normality test, the significance was confirmed through an independent samples T-test (parametric method) depending on whether the normality was satisfied or not.

[0097] 6-4) Research results 5α-reductase, which is known as a cause of hair loss, significantly decreased at all concentrations regardless of the concentration of heat-treated Lactobacillus fermentum LM1020 (p < 0.05). FGF7, FGF10, and EGF, which induce hair growth and hair development, significantly increased in the high-concentration treatment group of 1×10 9 cell / mL (p < 0.05). Therefore, it was confirmed that heat-treated Lactobacillus fermentum LM1020 is useful for preventing hair loss and promoting hair growth.

[0098] Example 7. Hair loss prevention effect of a functional raw material useful for alleviating hair loss symptoms and heat-treated Lactobacillus fermentum LM1020 The effect on the growth of dermal papilla cells was confirmed when elmentol, salicylic acid, and dexpanthol, which are active ingredients often used in functional cosmetics useful for alleviating hair loss symptoms, and heat-treated Lactobacillus fermentum LM1020 were used together. After inoculating dermal papilla cells in a 96-well plate and culturing them for 24 hours, the medium in the well was replaced with a medium lacking growth factors and additional culture was performed for 24 hours. Then, heat-treated Lactobacillus fermentum LM1020, elmentol, salicylic acid, and dexpanthol were used alone or mixed at a ratio of 3:2.6:2, and the effect on the growth of dermal papilla cells was confirmed by treating the dermal papilla cells prepared by the above method.

[0099] The growth rate when only dermal papilla cells were cultured and the growth rate of dermal papilla cells when treated with elmol, salicylic acid, dexapanthenol, and heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 alone or in combination were calculated. Then, the promoting effect of each treatment substance on the growth of dermal papilla cells was calculated using the following formula, and the effects were compared. All tests were repeated three times, and the average of each result was obtained and compared.

[0100] Promoting effect on dermal papilla cell growth (%) = (B - A) ÷ A × 100 A = Growth rate of dermal papilla cells in the untreated group B = Growth rate of dermal papilla cells when treated with elmol, salicylic acid, dexapanthenol, and heat-treated lactic acid bacterium Lactobacillus fermentum LM1020

[0101] As a result, among elmol, salicylic acid, and dexapanthenol, which are widely known to have a hair loss alleviating effect, elmol and salicylic acid were shown to inhibit the growth of dermal papilla cells. Dexapanthenol could promote the growth of dermal papilla cells, but its promoting effect on dermal papilla cell growth was lower than that of heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 at all concentrations. On the other hand, when heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 was treated together with a complex of elmol, salicylic acid, and dexapanthenol, it was confirmed that the inhibitory effect of the complex on the growth of dermal papilla cells could be overcome and the growth of dermal papilla cells could be promoted. To precisely grasp these synergistic effects, the effect predicted by Colby's formula was calculated, and it was verified whether a synergistic effect exceeding the predicted value could be obtained by comparing the predicted value with the actual measured value.

[0102] Colby's formula Predicted value = (A + B) - (A × B / 100) (Source: S.R. Colby, "Calculating Synergistic and Antagonistic Responses of Herbicide Combinations", Weeds 1967, 15, 20 - 22)

[0103] As a result, a mixture obtained by mixing elmol, salicylic acid, and dexpanthol at a ratio of 3:2.6:2 inhibited the growth of dermal papilla cells. However, when the mixture was treated together with heat-treated Lactobacillus fermentum LM1020, the growth of dermal papilla cells could be promoted. In addition, when the mixture and heat-treated Lactobacillus fermentum LM1020 were treated at 1×10 6 or 1×10 7 cell / mL, the effect of promoting the growth of dermal papilla cells was more excellent than when heat-treated Lactobacillus fermentum LM1020 was used alone.

[0104]

Table 3

[0105] Production Example 1. Development of a liquid preparation containing heat-treated Lactobacillus fermentum LM1020 A liquid preparation containing elmol, salicylic acid, and dexpanthol, which are the active ingredients of the hair loss-relieving functional cosmetic in which the synergistic effect was confirmed in Example 5 above, and heat-treated Lactobacillus fermentum LM1020, was developed. The developed liquid preparation contains 0.3% elmol, 0.26% salicylic acid, 0.2% dexpanthol, and 5% heat-treated Lactobacillus fermentum LM1020. In addition, purified water, ethanol, alanine / histidine / lysine polypeptide copper HCl (Alanine / Histidine / Lysine Polypeptide Copper HCl), polyacrylate crosspolymer-6, coconut acid, proline, tea tree oil, glycerin, peptide, butylene glycol, 1,2-hexanediol, green tea extract, lavender flower extract, pomegranate extract, ethylhexanediol, etc. were added and formulated.

[0106] Example 8. Assay of the hair loss-relieving effect through a human application test The human application test was conducted at the Global Medical Research Center Co., Ltd. and was carried out after obtaining approval from the Research Ethics Committee for the human application test (approval number: GIRB-21029-ET). The test participants were 25 Korean men and women aged 18 to 54, and 2 of them dropped out midway.

[0107] All participants applied the product of Production Example 1 evenly to the scalp before going to bed for 6 months and visited at intervals of 0, 8, 16, and 24 weeks to evaluate product use compliance, hair density measurement using a phototrichogram, visual evaluation by experts, and effectiveness questionnaire evaluation by participants (hair growth satisfaction, hair loss alleviation satisfaction, and front hairline satisfaction).

[0108] As a result of examining the product use compliance of the test subjects, it was confirmed that "0" test subjects used less than 80% based on the number of uses. Therefore, all participants applied the test product once a day as specified, before going to bed, to the scalp and used it during the 24-week test period.

[0109] The efficacy of the test product was verified by conducting hair density measurement (phototrichogram), photography and visual evaluation by experts, and effectiveness evaluation of use satisfaction. To measure the hair density, the depilated area to be evaluated was shaved into a 1 cm 2 circle, then a dot with a diameter of 1 mm was marked with ink, and photographed using a hair density measuring device. The hair density was measured 4 times every 8 weeks, and the number of hairs within a 1 cm 2 circle based on the ink mark was measured.

[0110] As a result, the hair density of the test participants increased continuously compared to before using the test product, and after 16 weeks, the hair density increased statistically significantly compared to before use (p < 0.05).

[0111]

Table 4

[0112] The macroscopic evaluation by experts was carried out by photographing the vertex (90°) and the frontal hairline (45°) which were the test sites. The macroscopic evaluation was performed by two experts, and the changes were evaluated on a 7-point scale. As a result, it was found that the test participants had the hair loss symptoms alleviated and the hair growth progressed as visually confirmed while using the test product. The precision of the research results was verified by confirming the degree of agreement of the macroscopic evaluation among researchers by the ICC (Intraclass Correlation Coefficients) method. As a result, the degree of agreement of the macroscopic evaluation among researchers showed that the intraclass correlation coefficient was 0.916, which was close to 1 representing perfect agreement.

[0113]

Table 5

[0114] After using the product, the effectiveness questionnaire evaluation of the test participants was carried out on a 7-point scale (-3 points: became very bad, -2 points: became bad, -1 point: became a little bad, 0 point: no change, 1 point: became a little better, 2 points: became better, 3 points: became very better). As a result, the participants who used the test product for a total of 24 weeks were satisfied with hair growth, hair loss alleviation and the frontal hairline, and showed a tendency that the satisfaction increased as the usage period increased.

[0115]

Table 6

[0116]

Table 7

[0117]

Table 8

[0118] Example 9. Changes in the scalp microbial environment before and after using a product containing heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 The scalp microbial environment before using the product of Production Example 1 and 24 weeks after use was compared. The scalp microorganisms were collected using a sterilized skin-microbiome collection swab, and immediately after collection, they were sent to a microbial analysis institution while maintaining low temperature using hexane transport medium. The analysis of scalp microorganisms was performed by preparing a library after sequencing and conducting 16S metagenome analysis for comparison.

[0119] As a result, in the test participants, the scalp lactic acid bacteria increased by four times after using the product of Production Example 1 (Fig. 7a). In addition, the diversity of scalp microorganisms was also improved. The total microbial diversity of the scalp increased by 60% (Fig. 7b), and the lactic acid bacteria diversity of the scalp increased by 176% (Fig. 7c). After using the product of Production Example 1, Staphylococcus caprae, a microorganism that decreases in people with alopecia areata, tended to increase (Figs. 7d and 7e). Therefore, it was confirmed that when the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 is applied to the scalp, it is possible to change the scalp microbial environment and prevent hair loss symptoms.

[0120] The above description of the present application is for illustrative purposes, and those having ordinary knowledge in the technical field to which the present application belongs should be able to understand that it can be easily deformed into other specific forms without changing the technical idea and essential features of the present application. Therefore, it should be understood that the above-described embodiments are illustrative in all respects and not restrictive. For example, each component described as a single type may be implemented dispersedly, and similarly, the components described as dispersed may also be implemented in a combined form.

Claims

1. A cosmetic composition for promoting the growth of dermal papilla cells, comprising heat-treated Lactobacillus rhamnosus fermentum LM1020 (KCCM12918P) as an active ingredient.

2. The cosmetic composition for promoting the growth of dermal papilla cells according to claim 1, wherein the heat-treated Lactobacillus rhamnosus fermentum LM1020 is derived from a fermented dough.

3. The cosmetic composition for promoting the growth of dermal papilla cells according to claim 1, wherein the heat-treated Lactobacillus rhamnosus fermentum LM1020 has a ratio of saturated fatty acid: unsaturated fatty acid: cyclic fatty acid of 0.1 to 2: 0.25 to 5: 0.03 to 0.

6.

4. The cosmetic composition for promoting the growth of dermal papilla cells according to claim 1, wherein the heat-treated Lactobacillus rhamnosus fermentum LM1020 increases the expression of CDK2, CDK4, cyclin B1 and cyclin D1.

5. The cosmetic composition for promoting the growth of dermal papilla cells according to claim 1, wherein the heat-treated Lactobacillus rhamnosus fermentum LM1020 decreases the expression level of the 5α-reductase-1 gene and increases the expression levels of the FGF7, FGF10 and EGF genes.

6. The cosmetic composition for promoting the growth of dermal papilla cells according to any one of claims 1 to 5, further comprising elmentol, salicylic acid and dexpanthol.

7. The heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 is 1 × 10 ６ cells / mL or 1 × 10 ７ cells / mL, and the cosmetic composition for promoting the growth of dermal papilla cells according to claim 6.

8. The cosmetic composition for promoting the growth of dermal papilla cells according to claim 6, further comprising purified water, ethanol, alanine / histidine / lysine polypeptide copper HCl (Alanine / Histidine / Lysine Polypeptide Copper HCl), polyacrylate crosspolymer-6, coconut acid, proline, tea tree oil, glycerin, peptide, butylene glycol, 1,2-hexanediol, green tea extract, lavender flower extract, carline extract and ethylhexanediol.

9. The cosmetic composition for promoting the growth of dermal papilla cells according to claim 8, which increases the microbial diversity and lactic acid bacteria diversity of the scalp.

10. A food composition for promoting the growth of dermal papilla cells, comprising heat-treated Lactobacillus rhamnosus fermentum LM1020 (KCCM12918P) as an active ingredient.

11. The food composition for promoting the growth of dermal papilla cells according to claim 10, wherein the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 is derived from a fermented dough.

12. The food composition for promoting the growth of dermal papilla cells according to claim 10, wherein the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 has a ratio of saturated fatty acid: unsaturated fatty acid: cyclic fatty acid of 0.1 to 2: 0.25 to 5: 0.03 to 0.

6.

13. A pharmaceutical composition for treating alopecia, comprising the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 (KCCM12918P) as an active ingredient.

14. The pharmaceutical composition for treating alopecia according to claim 13, wherein the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 is derived from a fermented dough.

15. The pharmaceutical composition for treating alopecia according to claim 13, wherein the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 has a ratio of saturated fatty acid: unsaturated fatty acid: cyclic fatty acid of 0.1 to 2: 0.25 to 5: 0.03 to 0.

6.

16. The pharmaceutical composition for treating alopecia according to claim 13, wherein the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 increases the expression of CDK2, CDK4, cyclin B1 and cyclin D1.

17. The pharmaceutical composition for treating alopecia according to claim 13, wherein the heat-treated lactic acid bacterium Lactobacillus fermentum LM1020 decreases the expression level of the 5α-reductase-1 gene and increases the expression levels of the FGF7, FGF10 and EGF genes.

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