WO2018135842A1 - Brevibacillus reuszeri strain exhibiting hair loss prevention, hair growth promotion or sexual function improvement capability, and composition containing same - Google Patents

Brevibacillus reuszeri strain exhibiting hair loss prevention, hair growth promotion or sexual function improvement capability, and composition containing same Download PDF

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WO2018135842A1
WO2018135842A1 PCT/KR2018/000756 KR2018000756W WO2018135842A1 WO 2018135842 A1 WO2018135842 A1 WO 2018135842A1 KR 2018000756 W KR2018000756 W KR 2018000756W WO 2018135842 A1 WO2018135842 A1 WO 2018135842A1
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composition
brevibacillus
strain
rugeri
ceb
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French (fr)
Korean (ko)
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염규진
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(주)코엔바이오
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/07—Bacillus

Definitions

  • the present invention relates to a novel strain having a hair loss prevention, promoting hair growth or improving sexual function and a composition comprising the same.
  • the cause of hair loss is not well known yet, but there are reports of possible causes such as genetic factors, hormonal abnormalities, and immunological abnormalities.
  • the present invention is to provide a novel strain effective for preventing hair loss, promoting hair growth or improving sexual function.
  • the present invention is to provide a composition for preventing hair loss, promoting hair growth or improving sexual function that can be safely used without side effects.
  • One aspect of the invention provides a novel Brevibacillus rugeri Brevibacillus reuszeri KCCM11911P strain.
  • the morphological characteristics of the strain are Gram-positive bacteria, have a nucleotide sequence of SEQ ID NO: 1, and have 99% homology with Brevibacillus rugeri as determined by 16s rRNA partial sequencing. Accordingly, the inventors deposited the newly isolated Brevibacillus rugeri Ceb-ch-003 at the Korean Culture Center of Microorganisms (120-861, Hongje-2ga-gil, Seodaemun-gu, Seoul) on October 7, 2016. Deposited with KCCM11911P.
  • the strain is isolated from the traditional Korean food Cheonggukjang, a kind of aerobic Bacillus subtilis. The strain is effective in preventing hair loss, promoting hair growth, improving sexual function, lowering cholesterol, and / or lipolysis.
  • Another aspect of the invention relates to a culture of Brevibacillus rugeri KCCM11911P, concentrates thereof, or dried products thereof.
  • the novel isolated strain of the present invention can be cultured through a conventional method for culturing Bacillus or Brevibacillus genus.
  • the medium may be natural or synthetic medium.
  • the carbon source of the medium for example, glucose, sucrose, dextrin, glycerol, starch and the like can be used, and as the nitrogen source, peptone, meat extract, yeast extract, dried yeast, soybean, ammonium salt, nitrate and other organic or inorganic Nitrogen containing compounds may be used, but are not limited to these components.
  • Inorganic salts contained in the medium include magnesium. Manganese, calcium. Iron, potassium and the like can be used, but are not limited thereto.
  • culture temperature conditions of the newly isolated strain of the present application can be incubated for 12 hours to 4 days in the temperature range of 20 ⁇ 40 °C.
  • medicinal preparations such as seotae, baekshou, succinct, licorice, celery, tofu, cinnamon, donkey, Seokpo, red squid, ephedra, ginger, white porcelain, cheoncho, horseback riding, mantis, etc.
  • culturing by adding a mixture thereof, by using the culture it is possible to further improve the effects of preventing hair loss, promoting hair growth, and improving sexual function of the present strain.
  • it is preferable to add frosted and / or white sewage to the culture medium and the amount thereof to be added is preferably 0.01 to 10% by weight, specifically 0.01 to 5% by weight, based on the weight of the medium, respectively.
  • the culture of the newly isolated strain may be a culture stock solution including the cells, and may also be a culture cell from which the culture supernatant is removed or concentrated.
  • the culture composition may further include components necessary for culturing Bacillus or Brevibacillus strains, as well as components that act synergistically to the growth of Bacillus or Brevibacillus strains, the composition according to the conventional It can be easily selected by those skilled in the art.
  • the state of the strain may be a liquid state or dry state
  • the drying method is possible, but not limited to ventilation drying, natural drying, spray drying and freeze drying.
  • the present invention relates to a composition
  • a composition comprising a Brevibacillus rugeri strain, a culture thereof, a concentrate thereof, or a dried product thereof.
  • the Brevibacillus rugeri strain is specifically, Brevibacillus rugeri Brevibacillus reuszeri KCCM11911P strain.
  • the composition may be a food composition or a pharmaceutical composition for preventing hair loss, promoting hair growth, or improving sexual function, and further, has a lipolytic effect and / or a cholesterol lowering effect.
  • One aspect of the food composition may be a food, health food, dietary supplement, or health functional food composition.
  • One aspect of the pharmaceutical composition may be a quasi-drug or a pharmaceutical preparation.
  • the composition is Seoryae, Baekshou, Sukjihwang, licorice, Cheongung, tofu, cinnamon, Angelica, Seokchangpo, Red sesame, ephedra, prickly pear, pine needles, pine flower, celticus, jimo, ginger, white porcelain, cheoncho, horseback riding, bay
  • Herbal ingredients effective for preventing hair loss or promoting hair growth such as herbal preparations such as a typewriter, extracts thereof, or mixtures thereof; Or may further comprise a pharmaceutical component such as minoxidil or finasteride.
  • the composition is Lactobacillus , Lactococcus , Propionibacterium , Enterocuccus , Strains such as the Bifidobacterium genus may be further included.
  • Enterococcus faecium e.g. KCCM11909P
  • Lactobacillus fermentum E.g. KCCM11910P
  • Enterococcus faecium e.g., KCCM11909P
  • Leuconostoc mesenteroides e.g. KCCM11827P
  • Lactobacillus sakei e.g. KCCM11841P
  • cultures thereof or mixtures thereof.
  • Lactobacillus fermentum Eg KCCM11910P
  • Leukonostock Mesenteroides KCCM11827P Lactobacillus sakei KCCM11841P, or cultures thereof, or mixtures thereof.
  • the composition may further comprise collagen.
  • the composition of the present invention comprises 5 x 10 4 to 5 x 10 10 CFU / ml Brevibacillus rugeri, specifically KCCM11911P strain at a concentration of 5 x 10 4 to 5 x 10 8 CFU / ml, preferably Comprises 1 ⁇ 10 6 to 1 ⁇ 10 9 CFU / ml of Brevibacillus rugeri (eg KCCM11911P).
  • An amount of 30 ml to 100 ml per dose of the strain composition may be administered to the subject once to four times a day.
  • composition of the present invention may further include a pharmaceutically or food acceptable carrier, and may be formulated with the carrier to be provided as a food or medicine.
  • the term "pharmaceutically or food acceptable carrier” refers to a carrier or diluent that does not stimulate the organism and does not inhibit the biological activity and properties of the administered strain.
  • composition may be formulated in a variety of oral or parenteral formulations, but may preferably be formulated in a liquid oral solution.
  • acceptable pharmaceutical or food acceptable carriers are sterile and physiologically compatible carriers, including saline, sterile water, buffered saline, albumin injectable solutions, dextrose solution, maltodextrin solution, glycerol and these
  • saline sterile and physiologically compatible carriers
  • sterile water sterile water
  • buffered saline albumin injectable solutions
  • dextrose solution dextrose solution
  • maltodextrin solution glycerol
  • glycerol glycerol
  • diluents, dispersants, surfactants, binders and lubricants may be additionally added to formulate into liquid formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.
  • binders, emulsifiers, preservatives, and the like may be further added to prevent degradation of the composition, or amino acids, vitamins, enzymes, flavoring agents, nonprotein nitrogen compounds, silicates, buffers, extractants, Oligosaccharides and the like may be further included.
  • the dosage is 5 x 10 4 to 5 x 10 8 CFU / ml Brevibacillus rugeri (e.g. KCCM11911P) strain, preferably 1 x 10 6 to 1 x 10 8 CFU / ml
  • the amount of Brevibacillus rugeri e.g., KCCM11911P
  • 50 ml per dose can be administered 2 to 4 times per day in an amount of 1 ⁇ 10 6 to 1 ⁇ 10 8 CFU / ml of Brevibacillus rugeri (eg KCCM11911P). More specifically, the amount of Brevibacillus rugeri (eg, KCCM11911P) of 1 ⁇ 10 6 to 1 ⁇ 10 8 CFU / ml may be administered once daily to 50ml to 100ml once or twice. More specifically, 1 x 10 6 to 1 x 10 8 CFU / ml Brevibacillus rugeri (e.g. KCCM11911P) is administered 50ml to 100ml once 30 minutes before breakfast, 50ml before dinner 30 minutes or before bedtime To 100 ml once.
  • 1 x 10 6 to 1 x 10 8 CFU / ml Brevibacillus rugeri e.g. KCCM11911P
  • Formulations for oral administration comprising the Brevibacillus rugeri of the present invention (eg KCCM11911P) include, for example, tablets, troches, lozenges, water-soluble or oily suspensions, prepared powders or granules, emulsions, hard or soft capsules. , Syrup or elixirs.
  • binders such as cellulose or gelatin
  • excipients such as dicalcium phosphate, disintegrants such as corn starch or sweet potato starch, stearic acid Lubricants such as magnesium, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax may be included, and the capsule formulation may further contain a liquid carrier such as fatty oil in addition to the aforementioned substances.
  • the daily dose of the composition or the Brevibacillus rugeri is dependent on the patient's weight, age, sex, health condition, treatment, prevention, or major symptoms, time of administration, method of administration and severity. Can vary from about 0.0001 mg / kg to about 10 g / kg, specifically about 0.01 mg / kg to about 500 mg / kg, once to six times daily, for example once to four times daily, or Applicable
  • Brevibacillus rugeri in the composition may be liquid or dry, preferably in liquid form. Drying methods may be, but not limited to, ventilation drying, natural drying, spray drying and freeze drying. Brevibacillus rugeri of the present invention (eg KCCM11911P) is in the form of a powder in the amount of 0.05 to 80% by weight, for example 0.1 to 70% by weight, 0.1 to 50% by weight, or 1 to 30% by weight of the composition Can be mixed.
  • One aspect of the present invention relates to a composition for preventing hair loss or promoting hair growth, comprising a Brevibacillus rugeri (eg, KCCM11911P) strain or a culture thereof, a concentrate thereof, or a dried product thereof.
  • a composition for preventing hair loss or promoting hair growth comprising a Brevibacillus rugeri (eg, KCCM11911P) strain or a culture thereof, a concentrate thereof, or a dried product thereof.
  • another aspect of the invention comprises administering to a subject a therapeutic or prophylactically effective amount of a Brevibacillus rugeri (eg, KCCM11911P) strain or culture thereof, concentrate or dried product thereof to prevent hair loss or promote hair growth It relates to a method for preventing hair loss or a method for treating hair loss.
  • the therapeutic or prophylactically effective amount may vary depending on the weight, age, sex, health condition, treatment, prevention, or major symptoms, time of administration, administration method, and severity of the patient, as described above.
  • a Brevibacillus rugeri of 5 ⁇ 10 4 to 5 ⁇ 10 8 CFU / ml (eg KCCM11911P) strain preferably 1 ⁇ 10 6 to 1 ⁇ 10 8 CFU / ml of Brevibacillus rugeri (eg : KCCM11911P) may be administered from 30ml to 100ml once to 4 times per day.
  • 50 ml per dose can be administered 2 to 4 times per day in an amount of 1 ⁇ 10 6 to 1 ⁇ 10 8 CFU / ml of Brevibacillus rugeri (eg KCCM11911P).
  • the amount of Brevibacillus rugeri (eg, KCCM11911P) of 1 ⁇ 10 6 to 1 ⁇ 10 8 CFU / ml may be administered once to twice daily with 50ml to 100ml per dose. More specifically, 1 x 10 6 to 1 x 10 8 CFU / ml Brevibacillus rugeri (e.g. KCCM11911P) is administered 50ml to 100ml once 30 minutes before breakfast, 50ml before dinner 30 minutes or before bedtime To 100 ml once.
  • KCCM11911P is administered 50ml to 100ml once 30 minutes before breakfast, 50ml before dinner 30 minutes or before bedtime To 100 ml once.
  • One aspect of the invention relates to a composition for improving sexual dysfunction, comprising Brevibacillus rugeri (eg KCCM11911P) strain or culture thereof, concentrate thereof or dried product thereof.
  • the sexual dysfunction improvement may be, for example, an improvement in erectile dysfunction.
  • another aspect of the invention comprises administering to a subject a therapeutic or prophylactically effective amount of a Brevibacillus rugeri (eg, KCCM11911P) strain or culture thereof, concentrate or dried product thereof, for the prevention or treatment of sexual dysfunction.
  • the therapeutic or prophylactically effective amount is the same as described above.
  • One aspect of the present invention relates to a composition for lowering cholesterol, comprising a Brevibacillus rugeri (eg, KCCM11911P) strain or a culture thereof, a concentrate thereof, or a dried product thereof.
  • a composition for lowering cholesterol comprising a Brevibacillus rugeri (eg, KCCM11911P) strain or a culture thereof, a concentrate thereof, or a dried product thereof.
  • administering to a subject a therapeutic or prophylactically effective amount of a Brevibacillus rugeri (e.g., KCCM11911P) strain or culture thereof, concentrate or dried product thereof for lowering cholesterol It relates to a method for preventing or treating cholesterol.
  • the therapeutic or prophylactically effective amount is the same as described above.
  • One aspect of the present invention relates to a composition for lipolysis, comprising a Brevibacillus rugeri (eg, KCCM11911P) strain or a culture thereof, a concentrate thereof, or a dried product thereof.
  • another aspect of the invention comprises administering to a subject for the prevention or treatment of hyperlipidemia a therapeutic or prophylactically effective amount of a Brevibacillus rugeri (eg, KCCM11911P) strain or culture thereof, concentrate thereof or dried product thereof.
  • a method for preventing or treating hyperlipidemia is the same as described above.
  • Brevibacillus rugeri eg KCCM11911P
  • KCCM11911P Brevibacillus rugeri
  • a composition comprising the same is effective for preventing hair loss, promoting hair growth or improving sexual function.
  • Brevibacillus rugeri eg KCCM11911P
  • a composition comprising the same can be used to prevent hair loss, promote hair growth, lower cholesterol or improve sexual function safely without side effects.
  • Figure 1 is a comparison of hair before and after taking Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain (about 1 month).
  • Figure 2 is a comparison of hair before and after taking Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain (about 1.5 months).
  • Figure 3 is a comparison of the hair before and after taking the Brevibacillus Rugeri Ceb-ch-003 (KCCM11911P) strain (about 3 months).
  • Figure 4 is a comparison of hair before and after taking Brevibacillus Rugeri Ceb-ch-003 (KCCM11911P) and Lactobacillus permanent Ceb-ch-002 (KCCM11910P).
  • FIG. 5 is a comparison of hair before and after taking Brevibacillus lugeri Ceb-ch-003 (KCCM11911P) and Lactobacillus permanent Ceb-ch-002 (KCCM11910P).
  • FIG. 6 is a comparison of hair before and after taking Brevibacillus lugeri Ceb-ch-003 (KCCM11911P) and Lactobacillus permanent Ceb-ch-002 (KCCM11910P).
  • FIG. 7 is a graph showing the NO production concentration compared to the Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain and other lactic acid strain Lactobacillus plantarum .
  • FIG. 8 is a graph showing the cholesterol lowering effect of the Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain and other lactic acid strain Lactobacillus plantarum .
  • Cheonggukjang a traditional Korean food, was collected, and the obtained sample was diluted in stages and incubated in BHI solid medium (Difco, USA) added with 3% sodium chloride for 24 hours at 37 ° C. The predominant strain was isolated from the sample. Selected colonies were purely separated by culturing in a new medium over 3 times, and the pure cultured cells were stored in a medium to which 20% glycerol was added and stored at below 70 ° C.
  • morphological and biochemical investigations were performed primarily.
  • the morphological features were Gram-stained and Gram-positive.
  • 16s rRNA partial sequencing was performed, and as a result, the nucleotide sequence of SEQ ID NO: 1, and the isolated strain was a type of aerobic Bacillus subtilis having 99% homology with Brevibacillus rugeri. It was confirmed to be.
  • the inventors deposited the newly isolated Brevibacillus rugeri Ceb-ch-003 at the Korean Culture Center of Microorganisms (120-861, Hongje-2ga-gil, Seodaemun-gu, Seoul) on October 7, 2016. Deposited with KCCM11911P.
  • strain powder The strain was lyophilized to prepare strain powder.
  • Ceb-ch-003 Inoculated with 0.2 to 0.4 liters in a sterile state and then incubated for 2 to 3 days at 35 ° C to obtain a culture solution of Brevibacillus Rugeri Ceb-ch-003.
  • Example 1 A breather ratio Bacillus Lu Jerry Ceb-ch-003 (KCCM11911P) 56 in the depilation symptoms strain culture aged, for a total of three male of 45 years old and 56 years of age and one month to two months obtained from 1 x 10 6
  • An amount of Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) to 1 ⁇ 10 8 CFU / ml was orally administered daily between 50 ml and 100 ml twice daily in the morning and evening.
  • the number of hairs falling out after hair washing once at 10-day intervals before and after administration of the strain was 10 days, 20 days and 30 days.
  • Hair loss number before and after taking Test subject Taking date 56 year old male 45 year old male 56 year old male Before taking 70 hair loss 49 hair loss 44 hair loss 10 days after taking 61 hair loss 40 hair loss 36 hair loss 20 days after taking 49 hair loss 29 hair loss 25 hair loss 30 days after taking 40 hair loss 19 hair loss 12 hair loss
  • the Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain of the present invention is effective in preventing hair loss, and is also effective in treating hair loss by remarkably improving hair thickness, quantity and shine.
  • Example 3 Brevibacillus Rugeri Ceb -ch-003 ( KCCM11911P ) Strains Lactobacillus Permanent Ceb -ch-002 ( KCCM11910P ) Hair loss prevention effect of strain combination
  • the culture solution of Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain obtained in Example 1 was isolated from Cheonggukjang and Korean Culture Center of Microorganisms, Hongje-2, Seodaemun-gu, Seoul, October 7, 2016.
  • a culture solution of Lactobacillus fermentum KCCM11910P strain deposited with accession number KCCM11910P to Ga-gil 120-861) was administered to a total of three males 55, 53 and 48 years old with alopecia for 1 month to 2 months. It was.
  • Specific dosing method is 1 x 10 6 to 1 x 10 8 CFU / ml Brevibacillus Rugeri Ceb-ch-003 (KCCM11911P) of 25ml to 50ml, 1 x 10 6 to 1 x 10 8 CFU / ml Lactobacillus fermentum KCCM11910P strain 25 ml to 50 ml per dose were administered orally twice daily.
  • Hair loss number before and after taking Test subject Taking date 55 year old male 53 year old male 48 year old male Before taking 60 hair loss 55 hair loss 57 hair loss 10 days after taking 45 hair loss 43 hair loss 45 hair loss 20 days after taking 23 hair loss 27 hair loss 36 hair loss 30 days after taking 10 hair loss 7 hair loss 13 hair loss
  • the Brevibacillus Rugeri Ceb-ch-003 (KCCM11911P) strains of the present invention when combined with other strains, Lactobacillus fermentum Ceb-ch-002 (KCCM11910P) strains, it is more effective in preventing hair loss. Can be.
  • KCCM11911P Brevibacillus rugeri Ceb-ch-003
  • KCCM11911P lyophilized powder of Brevibacillus rugeri Ceb-ch-003
  • Lactobacillus plantarum powder solution of 1 mg / ml to 5 mg / ml was used as a liquid and a control, respectively.
  • the cholesterol removal ability defined in the present invention can be specifically measured according to the following method:
  • the Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain powder of the present invention is effective in lowering cholesterol in proportion to the concentration, which is significantly improved compared to Lactobacillus plantarum , a lactic acid bacterium. .
  • Example 5 Brevibacillus Rugeri Ceb -ch-003 ( KCCM11911P ) Improvement of sexual function of strain And prevention effect
  • Lactobacillus plantarum 1 ⁇ g / ml 4.1 ( ⁇ M) 2.6 ( ⁇ M) 10 ⁇ g / ml 4.5 ( ⁇ M) 2.9 ( ⁇ M) 20 ⁇ g / ml 4.9 ( ⁇ M) 3.2 ( ⁇ M) 30 ⁇ g / ml 5.4 ( ⁇ M) 3.5 ( ⁇ M) 40 ⁇ g / ml 6.4 ( ⁇ M) 3.8 ( ⁇ M) 50 ⁇ g / ml 7.3 ( ⁇ M) 4.1 ( ⁇ M)

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Abstract

The present invention relates to a novel strain exhibiting a hair loss prevention, hair growth promotion or sexual function improvement capability, and a composition containing same.

Description

탈모 예방, 발모 촉진 또는 성기능 개선능이 있는 브레비바실러스 루제리 균주 및 이를 포함하는 조성물Brevibacillus rugeri strain having the ability to prevent hair loss, promote hair growth or improve sexual function and a composition comprising the same
본 발명은 탈모 예방, 발모 촉진 또는 성기능 개선능이 있는 신규한 균주 및 이를 포함하는 조성물에 관한 것이다.The present invention relates to a novel strain having a hair loss prevention, promoting hair growth or improving sexual function and a composition comprising the same.
현대 사회로 가면서 탈모 환자가 급격히 증가하고 있으며, 모발 관리 대상자 60%가 20-30대로 탈모의 연령대는 점점 낮아지고 있고, 탈모증으로 고통 받고 있는 환자의 숫자는 거의 천만 명에 이를 것으로 추산되고 있어 이에 따른 사회 경제적 문제가 심각하게 대두되고 있다.Hair loss is rapidly increasing in modern society, 60% of hair care subjects are in the 20s and 30s, and the age of hair loss is getting lower and the number of patients suffering from alopecia is estimated to reach almost 10 million. Socioeconomic problems are seriously emerging.
탈모가 심할수록 심리적으로 우울이나 불안 증상을 호소하며, 스트레스 지각도가 높아지고, 인간관계나 이성 관계에서 적응의 어려움을 겪으며, 가정 내 적응이 원만하지 못한 것으로 보고되고 있어 보건학적인 관심사가 되고 있다.The more severe the hair loss, the more psychological complaints of depression and anxiety symptoms, the higher the stress perception, the difficulty of adaptation in human or heterosexual relationship, and the adjustment in the home is reported as a health concern.
탈모의 원인은 아직까지 잘 알려져 있지 않으나 이에 대한 가능성 있는 원인으로 유전적 요인, 호르몬적 이상, 그리고 면역학적 이상에 의한 원인 등에 대한 보고가 있다.The cause of hair loss is not well known yet, but there are reports of possible causes such as genetic factors, hormonal abnormalities, and immunological abnormalities.
현재 탈모 치료제로는 미국 Food and Drug Administration(FDA)의 승인을 받은 경피도포용 미녹시딜(Minoxidil)과 경구투여용 Finasteride가 많이 사용되고 있으나 수반되는 부작용인 심혈관계 장애, 피부 자극, 성기능 감소 및 심각한 기형유발 등의 이유로 한계점을 드러내고 있다.Currently, the hair loss treatments are approved by the US Food and Drug Administration (FDA), and the transdermal application of minoxidil (Minoxidil) and orally administered Finasteride is used, but the associated side effects such as cardiovascular disorders, skin irritation, decreased sexual function and severe malformation It is showing its limitations for such reasons.
한편 선행 연구들에서 생약제제들을 이용한 탈모증 개선 효과에 대해 보고되어 왔으나, 그 결과는 미비한 수준이며 최근에 식물추출물질과 하수오 등 한방재료를 열수 추출하여 Lactobacillus 속 유산균으로 발효하여 이를 이용한 발모 촉진 연구와 특허가 일부 보고되고 있으나 대부분 실험쥐에 적용한 연구결과들이며 실제 탈모이거나 탈모가 진행 중인 사람에 적용한 연구는 전무한 실정이다. Meanwhile, previous studies have reported on the effect of improving alopecia using herbal medicines, but the results are inadequate. Recently, herbal extracts such as plant extracts and sewage were extracted with hot water and fermented with lactic acid bacteria of Lactobacillus genus. Although some patents have been reported, most of them have been applied to rats, and no studies have been applied to human hair loss or hair loss in progress.
이에, 본 발명은 탈모 예방, 발모 촉진 또는 성기능 개선에 효과적인 신규한 균주를 제공하고자 한다.Accordingly, the present invention is to provide a novel strain effective for preventing hair loss, promoting hair growth or improving sexual function.
나아가, 본 발명은 부작용 없이 안전하게 사용할 수 있는 탈모 예방, 발모 촉진용 또는 성기능 개선용 조성물을 제공하고자 한다. Furthermore, the present invention is to provide a composition for preventing hair loss, promoting hair growth or improving sexual function that can be safely used without side effects.
본 발명의 일 양태는, 신규한 브레비바실러스 루제리 Brevibacillus reuszeri KCCM11911P 균주를 제공한다. 상기 균주의 형태학적 특징은 그람 양성균이며, 서열번호 1의 염기 서열을 가지며, 16s rRNA partial sequencing에 의한 분석 결과 브레비바실러스 루제리와 99% 상동성을 갖는다. 이에 본 발명자들은 신규 분리한 브레비바실러스 루제리 Ceb-ch-003을 2016년 10월 7일 한국 미생물보존센터(Korean Culture Center of Microorganisms, 서울시 서대문구 홍제-2가-길 120-861)에 기탁번호 KCCM11911P로 기탁하였다. 상기 균주는 한국의 전통식품인 청국장으로부터 분리된 것으로, 호기성 고초균의 일종이다. 상기 균주는 탈모 예방, 발모 촉진, 성기능 개선, 콜레스테롤 저하, 및/또는 지방 분해에 효과적이다.One aspect of the invention provides a novel Brevibacillus rugeri Brevibacillus reuszeri KCCM11911P strain. The morphological characteristics of the strain are Gram-positive bacteria, have a nucleotide sequence of SEQ ID NO: 1, and have 99% homology with Brevibacillus rugeri as determined by 16s rRNA partial sequencing. Accordingly, the inventors deposited the newly isolated Brevibacillus rugeri Ceb-ch-003 at the Korean Culture Center of Microorganisms (120-861, Hongje-2ga-gil, Seodaemun-gu, Seoul) on October 7, 2016. Deposited with KCCM11911P. The strain is isolated from the traditional Korean food Cheonggukjang, a kind of aerobic Bacillus subtilis. The strain is effective in preventing hair loss, promoting hair growth, improving sexual function, lowering cholesterol, and / or lipolysis.
본 발명의 다른 양태로서 브레비바실러스 루제리 KCCM11911P의 배양물, 그의 농축물, 또는 그의 건조물에 관한 것이다.Another aspect of the invention relates to a culture of Brevibacillus rugeri KCCM11911P, concentrates thereof, or dried products thereof.
본 발명의 신규 분리한 균주는 통상적인 바실러스 또는 브레비바실러스 속 균의 배양방법을 통해 배양할 수 있다. 배지로는 천연배지 또는 합성배지를 사용할 수 있다. 배지의 탄소원으로는 예를 들어, 글루코오스, 수크로오스, 덱스트린, 글리세롤, 녹말 등이 사용될 수 있고, 질소원으로는 펩톤, 육류 추출물, 효모 추출물, 건조된 효모, 대두, 암모늄염, 나이트레이트 및 기타 유기 또는 무기 질소 함유 화합물이 사용될 수 있으나, 이러한 성분에 한정되는 것은 아니다. 배지에 포함되는 무기염으로는 마그네슘. 망간, 칼슘. 철, 칼륨 등이 사용될 수 있으나, 이들에 한정되는 것은 아니다. 상기 탄소원, 질소원 및 무기염의 성분 이외에 아미노산, 비타민, 핵산 및 그와 관련된 화합물들이 배지에 첨가될 수 있다. 본원의 신규 분리한 균주의 배양온도 조건은 20~40℃의 온도 범위에서 12시간 내지 4일간 배양할 수 있다. 일 예에서, 배양 배지에 서리태, 백하수오, 숙지황, 감초, 천궁, 두충, 계피, 당귀, 석창포, 적하수오, 측백엽, 생강, 백자인, 천초, 승마, 만형자 등의 생약 제제, 이의 추출물, 또는 이의 혼합물을 첨가하여 배양하고, 상기 배양물을 사용함으로써 본 균주의 탈모방지, 발모 촉진, 성기능 개선의 효과를 보다 개선할 수 있다. 특히, 배양 배지에 서리태 및/또는 백하수오를 첨가하는 것이 좋으며, 첨가되는 이의 양은, 각각 배지 중량을 기준으로 0.01 중량% 내지 10 중량%, 구체적으로는 0.01 중량% 내지 5 중량% 정도가 좋다. The novel isolated strain of the present invention can be cultured through a conventional method for culturing Bacillus or Brevibacillus genus. The medium may be natural or synthetic medium. As the carbon source of the medium, for example, glucose, sucrose, dextrin, glycerol, starch and the like can be used, and as the nitrogen source, peptone, meat extract, yeast extract, dried yeast, soybean, ammonium salt, nitrate and other organic or inorganic Nitrogen containing compounds may be used, but are not limited to these components. Inorganic salts contained in the medium include magnesium. Manganese, calcium. Iron, potassium and the like can be used, but are not limited thereto. In addition to the components of the carbon source, nitrogen source and inorganic salts, amino acids, vitamins, nucleic acids and related compounds may be added to the medium. Culture temperature conditions of the newly isolated strain of the present application can be incubated for 12 hours to 4 days in the temperature range of 20 ~ 40 ℃. In one embodiment, medicinal preparations such as seotae, baekshou, succinct, licorice, celery, tofu, cinnamon, donkey, Seokpo, red squid, ephedra, ginger, white porcelain, cheoncho, horseback riding, mantis, etc. By culturing by adding a mixture thereof, by using the culture, it is possible to further improve the effects of preventing hair loss, promoting hair growth, and improving sexual function of the present strain. In particular, it is preferable to add frosted and / or white sewage to the culture medium, and the amount thereof to be added is preferably 0.01 to 10% by weight, specifically 0.01 to 5% by weight, based on the weight of the medium, respectively.
신규 분리한 균주의 배양물은 균체를 포함한 배양 원액일 수 있으며, 또한 배양 상등액을 제거하거나 농축한 균체일 수 있다. 상기 배양물의 조성은 통상의 바실러스나 브레비바실러스 균주 배양에 필요한 성분뿐 아니라, 바실러스나 브레비바실러스 균주의 생장에 상승적으로 작용하는 성분을 추가적으로 포함할 수 있으며, 이에 따른 조성은 당업계의 통상의 기술을 가진 자에 의하여 용이하게 선택될 수 있다. The culture of the newly isolated strain may be a culture stock solution including the cells, and may also be a culture cell from which the culture supernatant is removed or concentrated. The culture composition may further include components necessary for culturing Bacillus or Brevibacillus strains, as well as components that act synergistically to the growth of Bacillus or Brevibacillus strains, the composition according to the conventional It can be easily selected by those skilled in the art.
또한 균주의 상태는 액상상태 또는 건조상태일 수 있으며, 건조방법은 통풍건조, 자연건조, 분무건조 및 동결건조가 가능하지만, 이에 제한되는 것은 아니다.In addition, the state of the strain may be a liquid state or dry state, the drying method is possible, but not limited to ventilation drying, natural drying, spray drying and freeze drying.
다른 양태로서 본 발명의 브레비바실러스 루제리 균주, 이의 배양물, 이의 농축물, 또는 이의 건조물을 포함하는 조성물에 관한 것이다. 상기 브레비바실러스 루제리 균주는 구체적으로, 브레비바실러스 루제리 Brevibacillus reuszeri KCCM11911P 균주일 수 있다. 상기 조성물은 탈모방지, 발모 촉진, 또는 성기능 개선용 식품 조성물 또는 의약 조성물일 수 있으며, 추가로, 지방 분해 효과 및/또는 콜레스테롤 저하 효과가 있다. 식품 조성물의 일 양태로는 식품, 건강식품, 건강보조식품, 또는 건강기능성 식품 조성물일 수 있다. 의약 조성물의 일 양태로는 의약외품 또는 의약적 제제일 수 있다. In another aspect, the present invention relates to a composition comprising a Brevibacillus rugeri strain, a culture thereof, a concentrate thereof, or a dried product thereof. The Brevibacillus rugeri strain is specifically, Brevibacillus rugeri Brevibacillus reuszeri KCCM11911P strain. The composition may be a food composition or a pharmaceutical composition for preventing hair loss, promoting hair growth, or improving sexual function, and further, has a lipolytic effect and / or a cholesterol lowering effect. One aspect of the food composition may be a food, health food, dietary supplement, or health functional food composition. One aspect of the pharmaceutical composition may be a quasi-drug or a pharmaceutical preparation.
일 예에서, 상기 조성물은 서리태, 백하수오, 숙지황, 감초, 천궁, 두충, 계피, 당귀, 석창포, 적하수오, 측백엽, 가시오가피, 송엽, 송화, 교맥, 지모, 생강, 백자인, 천초, 승마, 만형자 등의 생약 제제, 이의 추출물, 또는 이의 혼합물 등과 같이 탈모 방지 또는 발모 촉진에 효과적인 생약 성분; 또는 미녹시딜이나 finasteride 같은 의약 성분을 추가로 포함할 수 있다. In one embodiment, the composition is Seoryae, Baekshou, Sukjihwang, licorice, Cheongung, tofu, cinnamon, Angelica, Seokchangpo, Red sesame, ephedra, prickly pear, pine needles, pine flower, celticus, jimo, ginger, white porcelain, cheoncho, horseback riding, bay Herbal ingredients effective for preventing hair loss or promoting hair growth, such as herbal preparations such as a typewriter, extracts thereof, or mixtures thereof; Or may further comprise a pharmaceutical component such as minoxidil or finasteride.
다른 예에서, 상기 조성물은, Lactobacillus 속, Lactococcus 속, Propionibacterium 속, Enterocuccus 속, Bifidobacterium 속 등의 균주를 추가로 포함할 수 있다. 구체적으로, Enterococcus faecium(예: KCCM11909P), Lactobacillus fermentum (예: KCCM11910P), Enterococcus faecium(예: KCCM11909P), 류코노스톡 메센테로이데스(Leuconostoc mesenteroides)(예: KCCM11827P), 락토바실러스 사케이(Lactobacillus sakei)(예: KCCM11841P), 또는 이의 배양물, 또는 이의 혼합물을 추가로 포함할 수 있다. 더욱, 구체적으로는, Lactobacillus fermentum (예: KCCM11910P), 류코노스톡 메센테로이데스 KCCM11827P, 락토바실러스 사케이 KCCM11841P, 또는 이의 배양물, 또는 이의 혼합물을 추가로 포함할 수 있다. 또한, 상기 조성물은 콜라겐을 추가로 포함할 수 있다.In another embodiment, the composition is Lactobacillus , Lactococcus , Propionibacterium , Enterocuccus , Strains such as the Bifidobacterium genus may be further included. Specifically, Enterococcus faecium (e.g. KCCM11909P), Lactobacillus fermentum (E.g. KCCM11910P), Enterococcus faecium (e.g., KCCM11909P), Leuconostoc mesenteroides (e.g. KCCM11827P), Lactobacillus sakei (e.g. KCCM11841P), or cultures thereof, or mixtures thereof. Can be. More specifically, Lactobacillus fermentum (Eg KCCM11910P), Leukonostock Mesenteroides KCCM11827P, Lactobacillus sakei KCCM11841P, or cultures thereof, or mixtures thereof. In addition, the composition may further comprise collagen.
본 발명의 조성물은 5 x 104 내지 5 x 1010 CFU/ml의 브레비바실러스 루제리, 구체적으로는 KCCM11911P 균주를 5 x 104 내지 5 x 108 CFU/ml의 농도로 포함하며, 바람직하게는 1 x 106 내지 1 x 109 CFU/ml의 브레비바실러스 루제리 (예: KCCM11911P)을 포함한다. 상기 균주 조성물의 회당 30ml 내지 100ml의 양을 1일 1회 내지 4회 대상체에 투여할 수 있다.The composition of the present invention comprises 5 x 10 4 to 5 x 10 10 CFU / ml Brevibacillus rugeri, specifically KCCM11911P strain at a concentration of 5 x 10 4 to 5 x 10 8 CFU / ml, preferably Comprises 1 × 10 6 to 1 × 10 9 CFU / ml of Brevibacillus rugeri (eg KCCM11911P). An amount of 30 ml to 100 ml per dose of the strain composition may be administered to the subject once to four times a day.
본 발명의 조성물은 약학적으로 혹은 식품학적으로 허용 가능한 담체를 추가로 포함할 수 있으며, 담체와 함께 제제화되어 식품 혹은 의약품으로 제공될 수 있다. The composition of the present invention may further include a pharmaceutically or food acceptable carrier, and may be formulated with the carrier to be provided as a food or medicine.
본 발명에서 용어, "약학적으로 혹은 식품학적으로 허용 가능한 담체"란 생물체를 자극하지 않고 투여 균주의 생물학적 활성 및 특성을 저해하지 않는 담체 또는 희석제를 말한다. As used herein, the term "pharmaceutically or food acceptable carrier" refers to a carrier or diluent that does not stimulate the organism and does not inhibit the biological activity and properties of the administered strain.
상기 조성물은 경구 또는 비경구의 여러가지 제형으로 제제화될 수 있으나, 바람직하게는 액상 경구 용액으로 제형화될 수 있다. The composition may be formulated in a variety of oral or parenteral formulations, but may preferably be formulated in a liquid oral solution.
액상 용액으로 제제화되는 경우, 허용되는 약제학적 혹은 식품학적 허용 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 완충식염수, 알부민 주사용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 액상 제형, 환약, 캡슐, 과립 또는 정제로 제제화 할 수 있다. 또한 조성물의 품질 저하를 방지하기 위하여 결착제, 유화제, 보존제 등을 추가로 첨가할 수 있고, 또는, 아미노산제, 비타민제, 효소제, 향미제, 비단백질태 질소화합물, 규산염제, 완충제, 추출제, 올리고당 등을 추가로 포함할 수 있다. 액상 형태로 투여하는 경우의 투여량은 5 x 104 내지 5 x 108 CFU/ml의 브레비바실러스 루제리 (예: KCCM11911P) 균주, 바람직하게는 1 x 106 내지 1 x 108 CFU/ml의 브레비바실러스 루제리 (예: KCCM11911P)의 양으로 회당 30ml 내지 100ml를 1일 1회 내지 4회 투여할 수 있다. 일 예에서, 1 x 106 내지 1 x 108 CFU/ml의 브레비바실러스 루제리 (예: KCCM11911P)의 양으로 회당 50ml를 1일 2회 내지 4회 투여할 수 있다. 보다 구체적으로는 1 x 106 내지 1 x 108 CFU/ml의 브레비바실러스 루제리(예: KCCM11911P)의 양을 회당 50ml 내지 100ml를 1일 1회 내지 2회 투여할 수 있다. 보다 더욱 구체적으로는 1 x 106 내지 1 x 108 CFU/ml의 브레비바실러스 루제리 (예: KCCM11911P)를 아침 식전 30분에 50ml 내지 100ml 1회 투여하고, 저녁 식전 30분 또는 취침 전에 50ml 내지 100ml 1회 투여할 수 있다.When formulated in a liquid solution, acceptable pharmaceutical or food acceptable carriers are sterile and physiologically compatible carriers, including saline, sterile water, buffered saline, albumin injectable solutions, dextrose solution, maltodextrin solution, glycerol and these One or more components may be mixed and used, and other conventional additives such as antioxidants, buffers and bacteriostatic agents may be added as necessary. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to formulate into liquid formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. In addition, binders, emulsifiers, preservatives, and the like may be further added to prevent degradation of the composition, or amino acids, vitamins, enzymes, flavoring agents, nonprotein nitrogen compounds, silicates, buffers, extractants, Oligosaccharides and the like may be further included. When administered in liquid form, the dosage is 5 x 10 4 to 5 x 10 8 CFU / ml Brevibacillus rugeri (e.g. KCCM11911P) strain, preferably 1 x 10 6 to 1 x 10 8 CFU / ml The amount of Brevibacillus rugeri (e.g., KCCM11911P) may be administered from 30ml to 100ml per dose once to four times per day. In one example, 50 ml per dose can be administered 2 to 4 times per day in an amount of 1 × 10 6 to 1 × 10 8 CFU / ml of Brevibacillus rugeri (eg KCCM11911P). More specifically, the amount of Brevibacillus rugeri (eg, KCCM11911P) of 1 × 10 6 to 1 × 10 8 CFU / ml may be administered once daily to 50ml to 100ml once or twice. More specifically, 1 x 10 6 to 1 x 10 8 CFU / ml Brevibacillus rugeri (e.g. KCCM11911P) is administered 50ml to 100ml once 30 minutes before breakfast, 50ml before dinner 30 minutes or before bedtime To 100 ml once.
본 발명의 브레비바실러스 루제리 (예: KCCM11911P)을 포함하는 경구 투여용 제형으로는, 예를 들어 정제, 트로키제, 로렌지, 수용성 또는 유성현탁액, 조제분말 또는 과립, 에멀젼, 하드 또는 소프트 캡슐, 시럽 또는 엘릭시르제를 들 수 있다. 정제 및 캡슐 등의 제형으로 제제화 하기 위해, 락토오스, 사카로오스, 솔비톨, 마니톨, 전분, 아밀로펙틴, 셀룰로오스 또는 젤라틴과 같은 결합제, 디칼슘 포스페이트와 같은 부형제, 옥수수 전분 또는 고구마 전분과 같은 붕해제, 스테아르산 마그네슘, 스테아르산 칼슘, 스테아릴푸마르산 나트륨 또는 폴리에틸렌글리콜 왁스와 같은 윤활제를 포함할 수 있으며, 캡슐 제형의 경우 상기 언급한 물질 외에도 지방유와 같은 액체 담체를 더 함유할 수 있다. Formulations for oral administration comprising the Brevibacillus rugeri of the present invention (eg KCCM11911P) include, for example, tablets, troches, lozenges, water-soluble or oily suspensions, prepared powders or granules, emulsions, hard or soft capsules. , Syrup or elixirs. For formulation into tablets and capsules, such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, binders such as cellulose or gelatin, excipients such as dicalcium phosphate, disintegrants such as corn starch or sweet potato starch, stearic acid Lubricants such as magnesium, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax may be included, and the capsule formulation may further contain a liquid carrier such as fatty oil in addition to the aforementioned substances.
상기 조성물 또는 상기 브레비바실러스 루제리 (예: KCCM11911P)의 1일 투여량은 환자의 체중, 연령, 성별, 건강상태, 치료, 예방, 또는 개선하고자 하는 주요 증상, 투여시간, 투여 방법, 중증도에 따라 달라질 수 있으나, 약 0.0001mg/kg 내지 약 10g/kg, 구체적으로는 약 0.01 mg/kg 내지 약 500mg/kg일 수 있으며, 하루 1회 내지 6회, 예컨데, 하루 1회 내지 4회 투여 혹은 적용할 수 있다. The daily dose of the composition or the Brevibacillus rugeri (e.g. KCCM11911P) is dependent on the patient's weight, age, sex, health condition, treatment, prevention, or major symptoms, time of administration, method of administration and severity. Can vary from about 0.0001 mg / kg to about 10 g / kg, specifically about 0.01 mg / kg to about 500 mg / kg, once to six times daily, for example once to four times daily, or Applicable
상기 조성물 내 브레비바실러스 루제리 (예: KCCM11911P)는 액상 또는 건조상태일 수 있으며, 바람직하게는 액상 형태이다. 건조방법은 통풍건조, 자연건조, 분무건조 및 동결건조가 가능하지만, 이에 제한되는 것은 아니다. 본 발명의 브레비바실러스 루제리 (예: KCCM11911P)은 분말형태로 조성물 중량의 0.05 내지 80 중량%, 예를 들어, 0.1 내지 70 중량%, 0.1 내지 50 중량%, 또는 1 내지 30 중량%의 양으로 혼합될 수 있다. Brevibacillus rugeri (eg KCCM11911P) in the composition may be liquid or dry, preferably in liquid form. Drying methods may be, but not limited to, ventilation drying, natural drying, spray drying and freeze drying. Brevibacillus rugeri of the present invention (eg KCCM11911P) is in the form of a powder in the amount of 0.05 to 80% by weight, for example 0.1 to 70% by weight, 0.1 to 50% by weight, or 1 to 30% by weight of the composition Can be mixed.
본 발명의 일 양태는, 브레비바실러스 루제리 (예: KCCM11911P) 균주 또는 이의 배양물, 이의 농축액 또는 이의 건조물을 포함하는, 탈모 방지 혹은 발모 촉진용 조성물에 관한 것이다. 또는 본 발명의 다른 양태는, 브레비바실러스 루제리 (예: KCCM11911P) 균주 또는 이의 배양물, 이의 농축액 또는 이의 건조물의 치료적 또는 예방적 유효량을 탈모 방지 또는 발모 촉진을 위해 대상체에 투여하는 것을 포함하는, 탈모 방지 방법 혹은 탈모 치료 방법에 관한 것이다. 상기 치료적 또는 예방적 유효량은 전술한 바와 같이, 환자의 체중, 연령, 성별, 건강상태, 치료, 예방, 또는 개선하고자 하는 주요 증상, 투여시간, 투여 방법, 중증도에 따라 달라질 수 있으나, 1일 약 0.0001mg/kg 내지 약 10g/kg, 구체적으로는 약 0.01 mg/kg 내지 약 500mg/kg일 수 있으며, 하루 1회 내지 6회, 예컨데, 하루 1회 내지 4회 투여 혹은 적용하는 것일 수 있다. 또는, 5 x 104 내지 5 x 108 CFU/ml의 브레비바실러스 루제리 (예: KCCM11911P) 균주, 바람직하게는 1 x 106 내지 1 x 108 CFU/ml의 브레비바실러스 루제리 (예: KCCM11911P)의 양으로 회당 30ml 내지 100ml를 1일 1회 내지 4회 투여할 수 있다. 일 예에서, 1 x 106 내지 1 x 108 CFU/ml의 브레비바실러스 루제리 (예: KCCM11911P)의 양으로 회당 50ml를 1일 2회 내지 4회 투여할 수 있다. 보다 구체적으로는 1 x 106 내지 1 x 108 CFU/ml의 브레비바실러스 루제리 (예: KCCM11911P)의 양을 회당 50ml 내지 100ml를 1일 1회 내지 2회 투여할 수 있다. 보다 더욱 구체적으로는 1 x 106 내지 1 x 108 CFU/ml의 브레비바실러스 루제리 (예: KCCM11911P)를 아침 식전 30분에 50ml 내지 100ml 1회 투여하고, 저녁 식전 30분 또는 취침 전에 50ml 내지 100ml 1회 투여할 수 있다. One aspect of the present invention relates to a composition for preventing hair loss or promoting hair growth, comprising a Brevibacillus rugeri (eg, KCCM11911P) strain or a culture thereof, a concentrate thereof, or a dried product thereof. Or another aspect of the invention comprises administering to a subject a therapeutic or prophylactically effective amount of a Brevibacillus rugeri (eg, KCCM11911P) strain or culture thereof, concentrate or dried product thereof to prevent hair loss or promote hair growth It relates to a method for preventing hair loss or a method for treating hair loss. The therapeutic or prophylactically effective amount may vary depending on the weight, age, sex, health condition, treatment, prevention, or major symptoms, time of administration, administration method, and severity of the patient, as described above. About 0.0001 mg / kg to about 10 g / kg, specifically about 0.01 mg / kg to about 500 mg / kg, and may be administered or applied once to six times a day, for example, once to four times a day. . Or a Brevibacillus rugeri of 5 × 10 4 to 5 × 10 8 CFU / ml (eg KCCM11911P) strain, preferably 1 × 10 6 to 1 × 10 8 CFU / ml of Brevibacillus rugeri (eg : KCCM11911P) may be administered from 30ml to 100ml once to 4 times per day. In one example, 50 ml per dose can be administered 2 to 4 times per day in an amount of 1 × 10 6 to 1 × 10 8 CFU / ml of Brevibacillus rugeri (eg KCCM11911P). More specifically, the amount of Brevibacillus rugeri (eg, KCCM11911P) of 1 × 10 6 to 1 × 10 8 CFU / ml may be administered once to twice daily with 50ml to 100ml per dose. More specifically, 1 x 10 6 to 1 x 10 8 CFU / ml Brevibacillus rugeri (e.g. KCCM11911P) is administered 50ml to 100ml once 30 minutes before breakfast, 50ml before dinner 30 minutes or before bedtime To 100 ml once.
본 발명의 일 양태는, 브레비바실러스 루제리 (예: KCCM11911P) 균주 또는 이의 배양물, 이의 농축액 또는 이의 건조물을 포함하는, 성기능 장애 개선용 조성물에 관한 것이다. 상기 성기능 장애 개선은, 예컨데, 발기 부전의 개선일 수 있다. 또는 본 발명의 다른 양태는, 브레비바실러스 루제리 (예: KCCM11911P) 균주 또는 이의 배양물, 이의 농축액 또는 이의 건조물의 치료적 또는 예방적 유효량을 성기능 장애 예방 혹은 치료를 위해 대상체에 투여하는 것을 포함하는, 성기능 장애의 예방 또는 치료 방법에 관한 것이다. 상기 치료적 또는 예방적 유효량은 상술한 것과 동일하다.One aspect of the invention relates to a composition for improving sexual dysfunction, comprising Brevibacillus rugeri (eg KCCM11911P) strain or culture thereof, concentrate thereof or dried product thereof. The sexual dysfunction improvement may be, for example, an improvement in erectile dysfunction. Or another aspect of the invention comprises administering to a subject a therapeutic or prophylactically effective amount of a Brevibacillus rugeri (eg, KCCM11911P) strain or culture thereof, concentrate or dried product thereof, for the prevention or treatment of sexual dysfunction. To prevent or treat sexual dysfunction. The therapeutic or prophylactically effective amount is the same as described above.
본 발명의 일 양태는, 브레비바실러스 루제리 (예: KCCM11911P) 균주 또는 이의 배양물, 이의 농축액 또는 이의 건조물을 포함하는, 콜레스테롤 저하용 조성물에 관한 것이다. 또는 본 발명의 다른 양태는, 브레비바실러스 루제리 (예: KCCM11911P) 균주 또는 이의 배양물, 이의 농축액 또는 이의 건조물의 치료적 또는 예방적 유효량을 콜레스테롤 저하를 위해 대상체에 투여하는 것을 포함하는, 고콜레스테롤혈증의 예방 또는 치료 방법에 관한 것이다. 상기 치료적 또는 예방적 유효량은 상술한 것과 동일하다.One aspect of the present invention relates to a composition for lowering cholesterol, comprising a Brevibacillus rugeri (eg, KCCM11911P) strain or a culture thereof, a concentrate thereof, or a dried product thereof. Or another aspect of the invention, comprising administering to a subject a therapeutic or prophylactically effective amount of a Brevibacillus rugeri (e.g., KCCM11911P) strain or culture thereof, concentrate or dried product thereof for lowering cholesterol It relates to a method for preventing or treating cholesterol. The therapeutic or prophylactically effective amount is the same as described above.
본 발명의 일 양태는, 브레비바실러스 루제리 (예: KCCM11911P) 균주 또는 이의 배양물, 이의 농축액 또는 이의 건조물을 포함하는, 지방 분해용 조성물에 관한 것이다. 또는 본 발명의 다른 양태는, 브레비바실러스 루제리 (예: KCCM11911P) 균주 또는 이의 배양물, 이의 농축액 또는 이의 건조물의 치료적 또는 예방적 유효량을 고지방증 예방 혹은 치료를 위해 대상체에 투여하는 것을 포함하는, 고지방증 예방 또는 치료 방법에 관한 것이다. 상기 치료적 또는 예방적 유효량은 상술한 것과 동일하다.One aspect of the present invention relates to a composition for lipolysis, comprising a Brevibacillus rugeri (eg, KCCM11911P) strain or a culture thereof, a concentrate thereof, or a dried product thereof. Or another aspect of the invention comprises administering to a subject for the prevention or treatment of hyperlipidemia a therapeutic or prophylactically effective amount of a Brevibacillus rugeri (eg, KCCM11911P) strain or culture thereof, concentrate thereof or dried product thereof It relates to a method for preventing or treating hyperlipidemia. The therapeutic or prophylactically effective amount is the same as described above.
본 발명의 브레비바실러스 루제리 (예: KCCM11911P) 균주 또는 이를 포함하는 조성물은 탈모 예방, 발모 촉진 또는 성기능 개선에 효과적이다.Brevibacillus rugeri (eg KCCM11911P) strain of the present invention or a composition comprising the same is effective for preventing hair loss, promoting hair growth or improving sexual function.
브레비바실러스 루제리 (예: KCCM11911P) 또는 이를 포함하는 조성물은, 부작용 없이 안전하게 탈모 예방, 발모 촉진, 콜레스테롤 저하 또는 성기능 개선에 사용될 수 있다.Brevibacillus rugeri (eg KCCM11911P) or a composition comprising the same, can be used to prevent hair loss, promote hair growth, lower cholesterol or improve sexual function safely without side effects.
도 1은 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P) 균주를 복용하기 전과 후(약 1개월)의 모발 비교 사진이다. Figure 1 is a comparison of hair before and after taking Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain (about 1 month).
도 2는 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P) 균주를 복용하기 전과 후(약 1.5개월)의 모발 비교 사진이다. Figure 2 is a comparison of hair before and after taking Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain (about 1.5 months).
도 3은 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P) 균주를 복용하기 전과 후(약 3개월)의 모발 비교 사진이다. Figure 3 is a comparison of the hair before and after taking the Brevibacillus Rugeri Ceb-ch-003 (KCCM11911P) strain (about 3 months).
도 4는 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P)와 락토바실러스 퍼멘텀 Ceb-ch-002 (KCCM11910P)을 복용하기 전과 후(약 45일후)의 모발 비교 사진이다. Figure 4 is a comparison of hair before and after taking Brevibacillus Rugeri Ceb-ch-003 (KCCM11911P) and Lactobacillus permanent Ceb-ch-002 (KCCM11910P).
도 5는 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P)와 락토바실러스 퍼멘텀 Ceb-ch-002 (KCCM11910P)을 복용하기 전과 후(약 45일후)의 모발 비교 사진이다. FIG. 5 is a comparison of hair before and after taking Brevibacillus lugeri Ceb-ch-003 (KCCM11911P) and Lactobacillus permanent Ceb-ch-002 (KCCM11910P).
도 6는 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P)와 락토바실러스 퍼멘텀 Ceb-ch-002 (KCCM11910P)을 복용하기 전과 후(약 75일후)의 모발 비교 사진이다. FIG. 6 is a comparison of hair before and after taking Brevibacillus lugeri Ceb-ch-003 (KCCM11911P) and Lactobacillus permanent Ceb-ch-002 (KCCM11910P).
도 7은, 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P) 균주와 다른 유산균주인 Lactobacillus plantarum 대비 NO 생성 농도를 보여주는 그래프이다.7 is a graph showing the NO production concentration compared to the Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain and other lactic acid strain Lactobacillus plantarum .
도 8은, 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P) 균주와 다른 유산균주인 Lactobacillus plantarum 대비 콜레스테롤 저하 효과를 보여주는 그래프이다.8 is a graph showing the cholesterol lowering effect of the Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain and other lactic acid strain Lactobacillus plantarum .
이하, 실시예를 통하여 본 발명을 보다 상세히 설명하고자 한다. 그러나, 이들 실시 예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시 예에 국한되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.
실시예Example 1:  One: 브레비바실러스Brevibacillus 루제리Rugeri CebCeb -ch-003 (-ch-003 ( KCCM11911PKCCM11911P ) 균주의 분리 및 동정Isolation and Identification of Strains
(1) 시료 확보 및 균주 분리(1) Sample acquisition and strain isolation
한국의 전통식품인 청국장을 채취하고, 확보된 시료를 단계 희석하여 3% 염화나트륨이 첨가된 BHI 고체배지(Difco, USA)에 도말 후 37℃ 조건으로 24 시간 동안 배양하였다. 상기 시료에서 우점한 균주를 분리하였다. 선별된 콜로니는 3차에 걸쳐 새로운 배지에 옮겨 배양하는 방법으로 순수 분리하였으며, 순수 배양된 균을 20% 글리세롤이 첨가된 배지에 담아 영하 70℃ 이하에서 보존하였다.Cheonggukjang, a traditional Korean food, was collected, and the obtained sample was diluted in stages and incubated in BHI solid medium (Difco, USA) added with 3% sodium chloride for 24 hours at 37 ° C. The predominant strain was isolated from the sample. Selected colonies were purely separated by culturing in a new medium over 3 times, and the pure cultured cells were stored in a medium to which 20% glycerol was added and stored at below 70 ° C.
(2) 형태학적, 분류학적 특성 조사(2) Morphological and taxonomic characterization
상기 분리된 균주의 동정을 위하여, 일차적으로 형태학적, 생화학적 조사를 수행하였다. 형태적인 특징으로는 그람 염색결과 그람 양성이었다. 분류학적 특성을 분석하기 위하여 16s rRNA partial sequencing에 의해 분석을 실시하였으며, 그 결과 서열번호 1의 염기서열을 가지며, 당해 분리 균주는 브레비바실러스 루제리와 99%의 상동성을 갖는 호기성 고초균의 일종인 것으로 확인되었다.For identification of the isolated strains, morphological and biochemical investigations were performed primarily. The morphological features were Gram-stained and Gram-positive. In order to analyze the taxonomic characteristics, 16s rRNA partial sequencing was performed, and as a result, the nucleotide sequence of SEQ ID NO: 1, and the isolated strain was a type of aerobic Bacillus subtilis having 99% homology with Brevibacillus rugeri. It was confirmed to be.
이에 본 발명자들은 신규 분리한 브레비바실러스 루제리 Ceb-ch-003를 2016년 10월 7일 한국 미생물보존센터(Korean Culture Center of Microorganisms, 서울시 서대문구 홍제-2가-길 120-861)에 기탁번호 KCCM11911P로 기탁하였다. Accordingly, the inventors deposited the newly isolated Brevibacillus rugeri Ceb-ch-003 at the Korean Culture Center of Microorganisms (120-861, Hongje-2ga-gil, Seodaemun-gu, Seoul) on October 7, 2016. Deposited with KCCM11911P.
상기 균주를 동결건조하여 균주 분말을 제조하였다.The strain was lyophilized to prepare strain powder.
(3) 균주의 배양액의 제조(3) Preparation of culture medium of strain
브레비바실러스 루제리 Ceb-ch-003의 배양액을 다음과 같은 방법으로 제조하였다:Cultures of Brevibacillus rugeri Ceb-ch-003 were prepared by the following method:
정제수 100 리터에 Dextrose 2kg, 전지분유 1.5kg, 효모 추출액 0.05kg을 각각 첨가 후 121°C에서 15~30분간 고온·고압 멸균하고 35°C 내외로 식힌 후 브레비바실러스 루제리 Ceb-ch-003를 무균 상태에서 0.2~0.4 리터 접종한 다음 35°C 내외로 2~3일간 배양하여 브레비바실러스 루제리 Ceb-ch-003의 배양액을 수득하였다.After adding 2kg of Dextrose, 1.5kg of whole milk powder and 0.05kg of yeast extract to 100 liters of purified water, sterilization at high temperature and high pressure for 15-30 minutes at 121 ° C, and then cooled to around 35 ° C. Ceb-ch-003 Inoculated with 0.2 to 0.4 liters in a sterile state and then incubated for 2 to 3 days at 35 ° C to obtain a culture solution of Brevibacillus Rugeri Ceb-ch-003.
실시예Example 2:  2: 브레비바실러스Brevibacillus 루제리Rugeri CebCeb -ch-003 (-ch-003 ( KCCM11911PKCCM11911P ) 균주의 탈모 방지 효과) Hair Loss Prevention Effect
실시예 1에서 수득된 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P) 균주 배양액을 탈모 증상이 있는 56세, 45세 및 56세의 총 3명의 남성에게 1개월 내지 2개월 동안 1 x 106 내지 1 x 108 CFU/ml의 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P)의 양을 회당 50ml 내지 100ml를 아침 및 저녁으로 1일 2회 매일 경구 투여하였다.Example 1 A breather ratio Bacillus Lu Jerry Ceb-ch-003 (KCCM11911P) 56 in the depilation symptoms strain culture aged, for a total of three male of 45 years old and 56 years of age and one month to two months obtained from 1 x 10 6 An amount of Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) to 1 × 10 8 CFU / ml was orally administered daily between 50 ml and 100 ml twice daily in the morning and evening.
상기 균주의 투여 전과 복용의 10일, 20일 및 30일 후에 있어서 10일 간격으로 1회 머리 세정 후 빠지는 머리카락의 개수를 세었다.The number of hairs falling out after hair washing once at 10-day intervals before and after administration of the strain was 10 days, 20 days and 30 days.
상기 실험 결과는 아래 표 1과 같다:The experimental results are shown in Table 1 below:
복용 전후 탈모 숫자Hair loss number before and after taking
실험대상       Test subject 복용 일자Taking date 56세 남성56 year old male 45세 남성45 year old male 56세 남성56 year old male
복용 전Before taking 70개 탈모70 hair loss 49개 탈모49 hair loss 44개 탈모44 hair loss
복용 10일 후10 days after taking 61개 탈모61 hair loss 40개 탈모40 hair loss 36개 탈모36 hair loss
복용 20일 후20 days after taking 49개 탈모49 hair loss 29개 탈모29 hair loss 25개 탈모25 hair loss
복용 30일 후30 days after taking 40개 탈모40 hair loss 19개 탈모 19 hair loss 12개 탈모12 hair loss
또한, 상기 남성들에 있어서 본 발명의 균주의 투여 전과 투여 후의 특정 시점에 있어서, 모발의 굵기, 양, 윤기 등을 비교하고자 사진으로 촬영하였으며, 그 일부의 결과가 도 1 내지 도 3에 도시되어 있다.In addition, in the men before and after the administration of the strain of the present invention, at a specific time point, was taken with a picture to compare the thickness, amount, glossiness, etc. of the hair, a part of the results are shown in Figures 1 to 3 have.
상기 결과로부터, 본 발명의 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P)균주가 탈모 방지에 효과적이며, 또한, 모발 굵기와 양, 윤기를 현저히 개선하여 탈모 치료에 효과적임을 알 수 있다.From the above results, it can be seen that the Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain of the present invention is effective in preventing hair loss, and is also effective in treating hair loss by remarkably improving hair thickness, quantity and shine.
실시예Example 3:  3: 브레비바실러스Brevibacillus 루제리Rugeri CebCeb -ch-003 (-ch-003 ( KCCM11911PKCCM11911P ) 균주와 ) Strains 락토바실러스Lactobacillus 퍼멘텀Permanent CebCeb -ch-002 (-ch-002 ( KCCM11910PKCCM11910P ) 균주 배합의 탈모 방지 효과) Hair loss prevention effect of strain combination
실시예 1에서 수득된 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P) 균주의 배양액과, 청국장에서 분리되었으며 2016년 10월 7일 한국 미생물보존센터(Korean Culture Center of Microorganisms, 서울시 서대문구 홍제-2가-길 120-861)에 기탁번호 KCCM11910P로 기탁된 락토바실러스 퍼멘텀 Lactobacillus fermentum KCCM11910P 균주의 배양액을 탈모 증상이 있는 55세, 53세 및 48세의 총 3명의 남성에게 1개월 내지 2개월 동안 투여하였다. 구체적인 투여 방법은 1 x 106 내지 1 x 108 CFU/ml의 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P)를 회당 25ml 내지 50ml, 1 x 106 내지 1 x 108 CFU/ml의 락토바실러스 퍼멘텀 Lactobacillus fermentum KCCM11910P 균주를 회당 25ml 내지 50ml 1일 2회 매일 경구 투여하였다.The culture solution of Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain obtained in Example 1 was isolated from Cheonggukjang and Korean Culture Center of Microorganisms, Hongje-2, Seodaemun-gu, Seoul, October 7, 2016. A culture solution of Lactobacillus fermentum KCCM11910P strain deposited with accession number KCCM11910P to Ga-gil 120-861) was administered to a total of three males 55, 53 and 48 years old with alopecia for 1 month to 2 months. It was. Specific dosing method is 1 x 10 6 to 1 x 10 8 CFU / ml Brevibacillus Rugeri Ceb-ch-003 (KCCM11911P) of 25ml to 50ml, 1 x 10 6 to 1 x 10 8 CFU / ml Lactobacillus fermentum KCCM11910P strain 25 ml to 50 ml per dose were administered orally twice daily.
상기 균주들의 투여 전과 복용의 10일, 20일 및 30일 후에 있어서 10일 간격으로 1회 머리 세정 후 빠지는 머리카락의 개수를 세었다.The number of hairs falling out after hair washing once at 10-day intervals before and after 10, 20 and 30 days of dosing of the strains was counted.
상기 실험 결과는 아래 표 2과 같다:The experimental results are shown in Table 2 below:
복용 전후 탈모 숫자Hair loss number before and after taking
실험대상       Test subject 복용 일자Taking date 55세 남성55 year old male 53세 남성53 year old male 48세 남성48 year old male
복용 전Before taking 60개 탈모60 hair loss 55개 탈모55 hair loss 57개 탈모57 hair loss
복용 10일 후10 days after taking 45개 탈모45 hair loss 43개 탈모43 hair loss 45개 탈모45 hair loss
복용 20일 후20 days after taking 23개 탈모23 hair loss 27개 탈모27 hair loss 36개 탈모36 hair loss
복용 30일 후30 days after taking 10개 탈모10 hair loss 7개 탈모 7 hair loss 13개 탈모 13 hair loss
또한, 상기 남성들에 있어서 본 발명의 균주의 투여 전과 투여 후의 특정 시점에 있어서, 모발의 굵기, 양, 윤기 등을 비교하고자 사진으로 촬영하였으며, 그 일부의 결과가 도 4 내지 도 6에 도시되어 있다.In addition, in the men before and after the administration of the strain of the present invention, at a specific time point, was taken with a picture to compare the thickness, amount, glossiness, etc. of the hair, a part of the results are shown in Figures 4 to 6 have.
상기 결과로부터, 본 발명의 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P) 균주를 다른 균주, 락토바실러스 퍼멘텀 Lactobacillus fermentum Ceb-ch-002 (KCCM11910P) 균주와 병용시 탈모 방지에 더욱 효과적임을 알 수 있다.From the above results, the Brevibacillus Rugeri Ceb-ch-003 (KCCM11911P) strains of the present invention, when combined with other strains, Lactobacillus fermentum Ceb-ch-002 (KCCM11910P) strains, it is more effective in preventing hair loss. Can be.
실시예Example 4:  4: 브레비바실러스Brevibacillus 루제리Rugeri CebCeb -ch-003 (-ch-003 ( KCCM11911PKCCM11911P ) 균주의 콜레스테롤 저하 효과Cholesterol-lowering Effect of
브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P) 균주 분말의 콜레스테롤 저하 효과를 검토하기 위해, 각각 1mg/ml 내지 5mg/ml의 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P)의 동결건조 분말액, 및 대조군으로 각각 1mg/ml 내지 5mg/ml의 Lactobacillus plantarum 분말액을 사용하였다.To examine the cholesterol-lowering effects of Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain powder, lyophilized powder of Brevibacillus rugeri Ceb-ch-003 (KCCM11911P), respectively, from 1 mg / ml to 5 mg / ml Lactobacillus plantarum powder solution of 1 mg / ml to 5 mg / ml was used as a liquid and a control, respectively.
＜콜레스테롤(cholesterol) 제거능＞<Cholesterol removal ability>
본 발명에서 규정하는 콜레스테롤(cholesterol) 제거능은 구체적으로는 이하의 방법에 따라 측정할 수 있다: The cholesterol removal ability defined in the present invention can be specifically measured according to the following method:
MRS 배양지 30 ml를 50 ml용 팔콘(falcon) 튜브(tube)에 넣어 피검균 (글리세롤(glycerol) 스톡(stock))을 접종(1x107개／ml)해, 30℃으로 24시간 배양한다. 얻어진 배양액 300μl를 콜레스테롤(cholesterol) 배양지(350 mg／L 콜레스테롤(cholesterol)(Wako Pure Chemical), 0.2％담즙산(w／ｖ)을 포함한 MRS 배양지 30 ml에 첨가한다. 37℃으로 24시간 배양한 후, 4℃, 8,000 rpm에서 10분 원심분리(centrifugal separation)를 실시해, 상등액 중의 콜레스테롤 농도(cholesterol level)를 Determiner FC (Kyowa Medex Co., Ltd.)를 이용해 측정한다. 초기 콜레스테롤(cholesterol) 배양기 속에 함유되는 콜레스테롤 양(cholesterol)에 대한 배양지로부터 제거된 콜레스테롤 양(cholesterol)의 비율(％)을 산출한다. 30 ml of MRS culture paper is placed in a 50 ml falcon tube, and the test bacteria (glycerol stock) are inoculated (1 × 10 7 / ml) and incubated at 30 ° C. for 24 hours. 300 μl of the obtained culture was added to 30 ml of cholesterol culture medium (350 mg / L cholesterol (Wako Pure Chemical), MRS culture medium containing 0.2% bile acid (w / ｖ). , Centrifugal separation at 4 ° C., 8,000 rpm for 10 minutes, to determine the cholesterol level in the supernatant using Determiner FC (Kyowa Medex Co., Ltd.). The ratio (%) of cholesterol removed from the culture to the amount of cholesterol contained (cholesterol) is calculated.
그 결과는 아래 표 3 및 도 8에 도시되어 있으며, 이는 3회 반복 처리 후 평균값으로 나타낸 것이다. The results are shown in Table 3 below and FIG. 8, which is shown as the average value after three iterations.
상기 결과로부터 본 발명의 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P) 균주 분말이 농도에 비례해서 콜레스테롤 저하에 효과적이며, 이는 유산균인 Lactobacillus plantarum에 비해서 유의적으로 개선 효과가 높음을 알 수 있다.From the above results, it can be seen that the Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain powder of the present invention is effective in lowering cholesterol in proportion to the concentration, which is significantly improved compared to Lactobacillus plantarum , a lactic acid bacterium. .
브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P)Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) Lactobacillus Lactobacillus plantarumplantarum
1mg/ml1mg / ml 20%20% 11%11%
2mg/ml2mg / ml 25%25% 16%16%
3mg/ml3mg / ml 35%35% 22%22%
4mg/ml4mg / ml 49%49% 31%31%
5mg/ml5mg / ml 60%60% 35%35%
실시예Example 5:  5: 브레비바실러스Brevibacillus 루제리Rugeri CebCeb -ch-003 (-ch-003 ( KCCM11911PKCCM11911P )) 균주의 성기능 개선Improvement of sexual function of strain 및 예방And prevention 효과effect
성기능 이상 증상이 있거나 없는 흡연 또는 비흡연자인 50세 내지 70세의 총 5명의 남성에게 총 3개월 동안 1 x 106 내지 1 x 108 CFU/ml의 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P)를 회당 50ml 내지 100ml의 양으로 1일 1회 내지 2회 매일 경구 투여하였다. 상기 균주의 투여 전과 후에 있어서 한달 간격으로 새벽 발기 회수, 발기력, 발기 지속력 등을 자가 평가하게 하였다. A total of 5 males aged 50 to 70 who are smoking or non-smokers with or without sexual dysfunction have a total of 1 x 10 6 to 1 x 10 8 CFU / ml Brevibacillus lugeri Ceb-ch-003 ( KCCM11911P) was administered orally once to twice daily in an amount of 50 ml to 100 ml per time. Before and after the administration of the strain was allowed to self-evaluate the number of dawn erection, erection, erection persistence at monthly intervals.
이중 복용 1개월 내지 3개월 동안 설문에 응한 사람은 총 3명이었으며, 그 결과는 아래 표 4와 같다:A total of 3 people answered the questionnaire during the 1 to 3 months of dosing, and the results are shown in Table 4 below:
성기능 개선 효과 데이터Sexual function improvement effect data
실험대상Test subject 복용 지속일Dose duration 58세 남성58 year old male (비흡연자)(Non-smoker) 51세 남성51 year old male (비흡연자)(Non-smoker) 63세 남성63 year old male (흡연자)(smoker)
복용 전Before taking 발기력 낮음.Low erection. 발기력 양호Good erection 발기 어려움Erection difficulty
복용 1개월 후1 month after taking 새벽 발기Dawn erection 발기 지속력 증가Increased erection endurance 발기력 낮음 Low erection
복용 2개월 후2 months after taking 새벽 발기 회수 증가Dawn Erection Increase 발기 회수 증가Increased number of erections 새벽 발기Dawn erection
복용 3개월 후3 months after taking 발기 지속력 증가Increased erection endurance 발기 회수 및 발기 지속력 증가Increased number of erections and lasting erection 새벽 발기 회수 증가Dawn Erection Increase
상기 결과로부터 본 발명의 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P) 균주 분말을 지속적으로 복용시 성기능 이상의 예방 효과가 있으며, 나아가, 성기능 장애에 치료 효과가 있음을 확인할 수 있다.From the above results, continuous administration of Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) strain powder of the present invention has a prophylactic effect of sexual dysfunction, furthermore, it can be confirmed that there is a therapeutic effect on sexual dysfunction.
또한, 혈류 증가와 모세혈관 이완작용으로 발기력 향상에 도움을 주는 NO의 24시간 동안의 생성 농도(Hacat 세포로부터 발생) 정도를 추가 평가하였다. 본 발명의 신균주와 Lactobacillus plantarum과 비교 테스트(3회 반복 후 평균값)한 결과는 아래 표 5 및 도 7에 도시되어 있다. In addition, the 24 hour production concentration of NO (from Hacat cells), which helps improve erectile power by increasing blood flow and capillary relaxation, was further evaluated. Comparative results (average value after three iterations) of the new strain and Lactobacillus plantarum of the present invention are shown in Table 5 and FIG. 7 below.
브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P)Brevibacillus rugeri Ceb-ch-003 (KCCM11911P) Lactobacillus Lactobacillus plantarumplantarum
1μg/ml1 μg / ml 4.1(μM)4.1 (μM) 2.6(μM)2.6 (μM)
10μg/ml10 μg / ml 4.5(μM)4.5 (μM) 2.9(μM)2.9 (μM)
20μg/ml20 μg / ml 4.9(μM)4.9 (μM) 3.2(μM)3.2 (μM)
30μg/ml30 μg / ml 5.4(μM)5.4 (μM) 3.5(μM)3.5 (μM)
40μg/ml40 μg / ml 6.4(μM)6.4 (μM) 3.8(μM)3.8 (μM)
50μg/ml50 μg / ml 7.3(μM)7.3 (μM) 4.1(μM)4.1 (μM)
Figure PCTKR2018000756-appb-I000001
Figure PCTKR2018000756-appb-I000001
Figure PCTKR2018000756-appb-I000002
Figure PCTKR2018000756-appb-I000002
Figure PCTKR2018000756-appb-I000003
Figure PCTKR2018000756-appb-I000003

Claims (17)

  1. 브레비바실러스 루제리 Brevibacillus reuszeri Ceb-ch-003 (KCCM11911P) 균주. Brevibacillus rugeri Brevibacillus reuszeri Ceb-ch-003 (KCCM11911P) strain.
  2. 제1항에 있어서, 상기 균주는, 탈모 예방, 발모 촉진, 성기능 개선, 콜레스테롤 저하 또는 지방 분해에 사용되기 위한, 균주. The strain according to claim 1, wherein the strain is for use in preventing hair loss, promoting hair growth, improving sexual function, lowering cholesterol or lipolysis.
  3. 브레비바실러스 루제리 Ceb-ch-003 (KCCM11911P)의 배양물, 이의 농축물, 또는 이의 건조물.Culture of Brevibacillus rugeri Ceb-ch-003 (KCCM11911P), concentrates thereof, or dried products thereof.
  4. 브레비바실러스 루제리 균주, 이의 배양물, 이의 농축물, 또는 이의 건조물을 포함하는, 탈모 예방, 발모 촉진, 성기능 개선, 콜레스테롤 저하 또는 지방 분해용, 조성물.A composition for preventing hair loss, promoting hair growth, improving sexual function, lowering cholesterol or lipolysis, comprising a Brevibacillus rugeri strain, a culture thereof, a concentrate thereof, or a dried product thereof.
  5. 제4항에 있어서, 상기 브레비바실러스 루제리 균주가 브레비바실러스 루제리 Ceb-ch-003 (Brevibacillus reuszeri Ceb-ch-003: KCCM11911P)인, 조성물.The composition of claim 4, wherein the Brevibacillus rugeri strain is Brevibacillus rugeri Ceb-ch-003 ( Brevibacillus reuszeri Ceb-ch-003: KCCM11911P).
  6. 제4항에 있어서, 상기 조성물이 탈모 예방, 발모 촉진, 또는 성기능 개선용인, 조성물.The composition of claim 4, wherein the composition is for preventing hair loss, promoting hair growth, or improving sexual function.
  7. 제4항에 있어서, 상기 조성물이 의약 조성물 또는 식품 조성물인, 조성물. The composition of claim 4 wherein the composition is a pharmaceutical composition or a food composition.
  8. 제4항 내지 제7항 중 어느 하나의 항에 있어서, 상기 조성물이, 경구 또는 비경구 형태로 투여되는, 조성물.The composition of any one of claims 4 to 7, wherein the composition is administered in oral or parenteral form.
  9. 제4항 내지 제7항 중 어느 하나의 항에 있어서, 상기 브레비바실러스 루제리 균주가 1일 약 0.0001mg/kg 내지 약 10g/kg의 양으로 투여되는, 조성물.8. The composition of claim 4, wherein the Brevibacillus rugeri strain is administered in an amount of about 0.0001 mg / kg to about 10 g / kg per day. 9.
  10. 제4항 내지 제7항 중 어느 하나의 항에 있어서, 5 x 104 내지 5 x 108 CFU/ml의 브레비바실러스 루제리 균주가 회당 30ml 내지 100ml를 1일 1회 내지 4회 투여되는, 조성물.8. The Brevibacillus rugeri strain of claim 4 , wherein 5 × 10 4 to 5 × 10 8 CFU / ml of the Brevibacillus rugeri strain is administered from 30 ml to 100 ml once to four times daily. Composition.
  11. 제4항 내지 제7항 중 어느 하나의 항에 있어서, 상기 조성물이 약제학적으로 또는 식품학적으로 허용되는 담체를 추가로 포함하는, 조성물.8. The composition of claim 4, wherein the composition further comprises a pharmaceutically or food acceptable carrier. 9.
  12. 제4항 내지 제7항 중 어느 하나의 항에 있어서, 상기 조성물이, Lactobacillus 속, Lactococcus 속, Propionibacterium 속, Enterocuccus 속, 또는 Bifidobacterium 속의 균주를 추가로 포함하는, 조성물.The method according to any one of claims 4 to 7, wherein the composition is Lactobacillus , Lactococcus , Propionibacterium Further comprising a strain of the genus, Enterocuccus , or Bifidobacterium .
  13. 제12항에 있어서, 상기 조성물이, Lactobacillus fermentum 균주 또는 Enterococcus faecium 균주, 이의 배양물, 이의 농축물, 이의 건조물 또는 이의 혼합물을 추가로 포함하는, 조성물.The composition of claim 12, wherein the composition further comprises a Lactobacillus fermentum strain or Enterococcus faecium strain, a culture thereof, a concentrate thereof, a dried product thereof, or a mixture thereof.
  14. 제4항 내지 제7항 중 어느 하나의 항에 있어서, 상기 성기능 개선이 발기부전 개선인, 조성물. The composition of any one of claims 4 to 7, wherein the improvement in sexual function is an improvement in erectile dysfunction.
  15. 제4항 내지 제7항 중 어느 하나의 항에 있어서, 상기 브레비바실러스 루제리 균주가 청국장에서 분리된 것인, 조성물. The composition according to any one of claims 4 to 7, wherein the Brevibacillus rugeri strain is isolated in Cheonggukjang.
  16. 제4항 내지 제7항 중 어느 하나의 항에 있어서, 상기 브레비바실러스 루제리 균주는 조성물 중량의 0.05 내지 80 중량%로 포함된, 조성물.8. The composition of claim 4, wherein the Brevibacillus rugeri strain comprises from 0.05 to 80% by weight of the composition. 9.
  17. 제1항 또는 제2항에 있어서, 상기 브레비바실러스 루제리 Ceb-ch-003 (Lactobacillus fermentum Ceb-ch-002: KCCM11910P)이 서열번호 1의 염기서열을 갖는, 균주.The method according to claim 1 or 2, wherein the Brevibacillus rugeri Ceb-ch-003 ( Lactobacillus fermentum Ceb-ch-002: KCCM11910P) has a nucleotide sequence of SEQ ID NO: 1.
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