WO2023075458A1 - Nouvelle souche bactérienne, vésicules dérivées de celle-ci, et utilisation anti-inflammatoire et anti-bactérienne associées - Google Patents

Nouvelle souche bactérienne, vésicules dérivées de celle-ci, et utilisation anti-inflammatoire et anti-bactérienne associées Download PDF

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WO2023075458A1
WO2023075458A1 PCT/KR2022/016596 KR2022016596W WO2023075458A1 WO 2023075458 A1 WO2023075458 A1 WO 2023075458A1 KR 2022016596 W KR2022016596 W KR 2022016596W WO 2023075458 A1 WO2023075458 A1 WO 2023075458A1
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strain
endoplasmic reticulum
clostridium
lysate
culture medium
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PCT/KR2022/016596
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English (en)
Korean (ko)
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김정현
강기성
임나리
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주식회사 바이오뱅크힐링
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Priority claimed from KR1020210144399A external-priority patent/KR102337993B1/ko
Priority claimed from KR1020210144400A external-priority patent/KR102337991B1/ko
Priority claimed from KR1020210149529A external-priority patent/KR102337998B1/ko
Priority claimed from KR1020210153854A external-priority patent/KR102337995B1/ko
Application filed by 주식회사 바이오뱅크힐링 filed Critical 주식회사 바이오뱅크힐링
Publication of WO2023075458A1 publication Critical patent/WO2023075458A1/fr

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    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • 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
    • 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
    • C12R2001/145—Clostridium

Definitions

  • It relates to novel microorganisms, lysates thereof, culture solutions, extracts of culture solutions, endoplasmic reticulum, and anti-inflammatory and/or antibacterial uses thereof.
  • Microbiome refers to microorganisms existing in a specific environment and their entire genetic information, and refers to the collection of genomes that represent the entire genetic information of a single organism. Therefore, the human microbiome refers to microorganisms living inside and outside the human body and their genetic information.
  • Intestinal microbes supply nutrients that cannot be produced by the host's own enzymes alone, and are closely related to the host's metabolism and immune system, while preventing various diseases such as irritable bowel syndrome, obesity, atopy, depression, rheumatoid arthritis, autism spectrum disorder, and dementia. It has been reported to be associated with
  • the endoplasmic reticulum is a nano-sized material of about 20 to 200 nm produced and discharged by cells, and is free to move between cells.
  • the endoplasmic reticulum contains membrane lipids, membrane proteins, DNA or RNA, etc., and these genetic materials act as a complex to transmit toxic factors between cells and to regulate inflammation and immune responses. From single-celled organisms to multicellular organisms, information exchange between cells is an essential process of life. Recently, endoplasmic reticulum has been recognized as a medium for information exchange between cells, and methods for using vesicles as drug carriers have been developed.
  • Coprococcus eutactus Belonging to Coprococcus eutactus ( Coprococcus eutactus ) strain or deposited under accession number KCTC14723BP, Agatobaculum To provide a strain of Agathobaculum butyriciproducens belonging to the genus Agathobaculum sp .
  • Another aspect is to provide an endoplasmic reticulum derived from the strain, a lysate of the strain, or a culture medium.
  • Roseburia phaesis strain Clostridium reptum strain, Coprococcus eulactus strain, Agatobaculum butyriciproducens strain, endoplasmic reticulum derived from the strain, a lysate of the strain, a culture medium or their
  • a pharmaceutical composition for preventing or treating inflammatory diseases comprising the mixture as an active ingredient.
  • Roseburia phaesis strain Clostridium reptum strain, Coprococcus eulactus strain, Agatobaculum butyriciproducens strain, endoplasmic reticulum derived from the strain, a lysate of the strain, a culture medium or their To provide a health functional food for preventing or improving inflammatory diseases comprising the mixture as an active ingredient.
  • Another aspect is a strain of Roseburia paesis, a Clostridium reptum strain, a Coprococcus eulactus strain, an Agatobaculum butyriciproducens strain, an endoplasmic reticulum derived from the strain, a lysate of the strain, a culture medium, or these To provide a health functional food for improving intestinal health containing a mixture of as an active ingredient.
  • Another aspect is a strain of Roseburia paesis, a Clostridium reptum strain, a Coprococcus eulactus strain, an Agatobaculum butyriciproducens strain, an endoplasmic reticulum derived from the strain, a lysate of the strain, a culture medium, or these
  • a pharmaceutical composition for the prevention or treatment of bacterial infections comprising a mixture of as an active ingredient.
  • Another aspect is a strain of Roseburia paesis, a Clostridium reptum strain, a Coprococcus eulactus strain, an Agatobaculum butyriciproducens strain, an endoplasmic reticulum derived from the strain, a lysate of the strain, a culture medium, or these
  • an antibacterial composition for external application for skin comprising a mixture of.
  • Another aspect is a strain of Roseburia paesis, a Clostridium reptum strain, a Coprococcus eulactus strain, an Agatobaculum butyriciproducens strain, an endoplasmic reticulum derived from the strain, a lysate of the strain, a culture medium, or these
  • a health functional food for preventing or improving bacterial infection comprising a mixture of as an active ingredient.
  • Another aspect is a strain of Roseburia paesis, a Clostridium reptum strain, a Coprococcus eulactus strain, an Agatobaculum butyriciproducens strain, an endoplasmic reticulum derived from the strain, a lysate of the strain, a culture medium, or these To provide a method for preventing or treating an inflammatory disease by administering a mixture of to a subject in need thereof.
  • Another aspect is a strain of Roseburia paesis, a Clostridium reptum strain, a Coprococcus eulactus strain, an Agatobaculum butyriciproducens strain, an endoplasmic reticulum derived from the strain, a lysate of the strain, a culture medium, or these To provide a method for preventing or treating a bacterial infection by administering a mixture of to a subject in need thereof.
  • Another aspect is a strain of Roseburia paesis, a Clostridium reptum strain, a Coprococcus eulactus strain, an Agatobaculum butyriciproducens strain, an endoplasmic reticulum derived from the strain, a lysate of the strain, a culture medium, or these To provide a use for the preparation of a mixture of inflammatory diseases for the prevention or treatment of a composition.
  • Another aspect is a strain of Roseburia paesis, a Clostridium reptum strain, a Coprococcus eulactus strain, an Agatobaculum butyriciproducens strain, an endoplasmic reticulum derived from the strain, a lysate of the strain, a culture medium, or these To provide a use for the preparation of a composition for preventing or treating a bacterial infection of a mixture of.
  • Coprococcus eutactus Belonging to Coprococcus eutactus ( Coprococcus eutactus ) strain or deposited under accession number KCTC14723BP, Agatobaculum Agathobaculum butyriciproducens strain belonging to the genus Agathobaculum sp .
  • the Roseburia paesis strain may be a strain containing the 16S rRNA of SEQ ID NO: 1.
  • the Clostridium reptum strain may be a strain containing the 16S rRNA of SEQ ID NO: 2.
  • the Coprococcus eulactus strain may be a strain containing the 16S rRNA of SEQ ID NO: 3.
  • the Agatobaculum Butyrishproducens strain may be a strain containing the 16S rRNA of SEQ ID NO: 4.
  • the strain may have anti-inflammatory and/or antibacterial activity.
  • the strain inhibits the production of nitric oxide in inflammatory cells, inhibits the expression of inflammatory cytokines (eg, TNF- ⁇ or IL-6), or inhibits the growth of bacteria (eg, C. difficile ) may be suppressed.
  • the strain reduces inflammatory factors induced by C. difficile , such as pro-inflammatory cytokines (eg, TNF, or CCL2), or anti-inflammatory cytokines (eg, IL-10). ) may be increased.
  • Another aspect is the endoplasmic reticulum derived from the Roseburia paesis strain, Clostridium reptum strain, Coprococcus eulactus strain or Agatobaculum butyrishproducens strain, a lysate of the strain, a culture medium, an extract of the culture medium, or these provides a mixture of
  • the strain is as described above.
  • vesicle refers to particles secreted from cells and released into the extracellular space, including exosomes, ectosomes, microvesicles, and microparticles. , exosome like vesicles, and the like.
  • Extracellular endoplasmic reticulum can reflect the state of the secreting cell of origin (donor cell), show various biological activities depending on which cell it is secreted from, and play an important role in cell-to-cell interactions by transferring genetic material and proteins between cells. can do.
  • the endoplasmic reticulum is a membrane-structured endoplasmic reticulum, and the inside and the outside are divided, and has a plasma membrane lipid, a plasma membrane protein, a nucleic acid, and a cytoplasmic component of the cell, and is larger than the original cell. may be small.
  • the endoplasmic reticulum may be separated from a cell lysate of a culture solution of a Roseburia paesis strain, a Clostridium reptum strain, a Coprococcus eulactus strain, and an Agatobaculum butyriciproducens strain.
  • the extracellular vesicles may have a diameter of 10 nm to 400 nm.
  • it may be 10 nm to 400 nm, 10 nm to 350 nm, 10 nm to 300 nm, or 10 nm to 250 nm.
  • the term "culture medium” may be used interchangeably with “culture supernatant”, “conditioned culture medium” or “conditioned medium”, and may be used interchangeably with Roseburia paesis strains, Clostridium reptum strains, Coprococcus eustachus strains Or the entire strain, including the strain obtained by culturing the strain for a certain period of time in a medium capable of supplying nutrients so that the Agatobaculum butyriciproducens strain can grow and survive in vitro, its metabolites, and extra nutrients. can mean a badge.
  • the culture solution may mean a culture solution obtained by removing the cells from the cell culture solution obtained by culturing the strain.
  • the liquid from which the cells are removed from the culture solution is also called “supernatant”. It can be obtained by removing the precipitate and taking only the upper liquid.
  • the "cell” refers to the "strain” itself of the present invention, and includes the “strain” itself separated and selected from skin samples, etc., or the “strain” separated from the culture solution by culturing the "strain".
  • the cells can be obtained by centrifuging the culture solution and taking the part that has sunk in the lower layer, or it can be obtained by leaving it for a certain period of time and then removing the upper liquid as it sinks to the lower layer of the culture medium by gravity.
  • the culture solution may include a culture solution itself obtained by culturing the strain, a concentrate thereof, or a lyophilized product or a culture supernatant obtained by removing the strain from the culture solution, a concentrate thereof, or a lyophilisate.
  • the culture solution is obtained by culturing Roseburia paesis in an appropriate medium (eg, R2A medium or TSA medium) at any temperature above 10 ° C. or below 40 ° C. for a certain period of time, for example, 4 to 50 hours it could be
  • an appropriate medium eg, R2A medium or TSA medium
  • the culture supernatant of the strain may be obtained by centrifuging or filtering the strain culture medium to remove the strain.
  • the concentrate may be obtained by concentrating the supernatant obtained after filtering the strain culture medium itself, or the culture medium using a centrifugal separation or filter.
  • the culture medium and culture conditions for culturing the Roseburia paesis can be appropriately selected or modified by those skilled in the art.
  • lysate may mean a product obtained by disrupting the cell wall of the strain itself by chemical or physical force.
  • culture broth extract refers to an extract obtained from the culture medium or a concentrate thereof, and may include an extract, a dilution or concentrate of the extract, a dried product obtained by drying the extract, or a crude or purified product thereof, or a fraction obtained by fractionating the same.
  • Roseburia phaesis strain Clostridium reptum strain, Coprococcus eulactus strain or Agatobaculum butyrishproducens strain, endoplasmic reticulum derived from the strain, lysate, culture medium, or culture medium of the strain Provides the use of the extract for disease improvement, prevention or treatment.
  • the term "treat” may mean that an inflammation or bacterial infection is cured in a shorter time compared to natural healing.
  • the treatment may include amelioration and/or alleviation of inflammation or bacterial infections.
  • the treatment may refer to healing and/or recovery of symptoms caused by inflammation or bacterial infection.
  • prevention refers to partially or completely delaying or preventing the onset or recurrence of a disease, disorder, or its attendant symptoms, preventing the acquisition or re-acquisition of a disease or disorder, or preventing the occurrence or recurrence of a disease or disorder. means of reducing the risk of acquisition.
  • the prevention refers to any action that inhibits or delays the occurrence of inflammation or bacterial infection by administration of the composition according to the present invention.
  • Uses of the strain may include preventing, ameliorating, or treating inflammatory diseases (anti-inflammatory activity), preventing, ameliorating, or treating bacterial infections (antibacterial activity), or preventing or improving intestinal health.
  • inflammatory diseases anti-inflammatory activity
  • bacterial infections antibacterial activity
  • the inflammatory disease may include inflammation of the digestive system (gastrointestinal tract, etc.), inflammation of the eye, inflammation of the oral cavity, inflammation of the respiratory system including the lungs, inflammation of the skin, inflammation of the cardiovascular system, inflammation of the brain, inflammation of the ear, and the like. there is.
  • the inflammatory diseases include inflammatory bowel diseases (IBD); irritable bowel syndrome; Behcet's disease; enteritis, Crohn's disease; ulcerative colitis; vasculitis; mucositis; stomatitis; peri-implantitis; periodontitis; pulpitis; gingivitis; Pneumonia; dermatitis; atopic dermatitis; contact dermatitis; CREST syndrome; dermatitis herpetiformis; dermatomyositis; systemic scleroderma; erythema nodosum; Henoch-Schonlein purpura; Hidradenitis suppurativa; Lichen planus; Majeed syndrome; Schnitzler syndrome; psoriasis; eczema; acne; mouth ulcers; uveitis; pharyngitis; tonsillitis; otitis, including otitis media; psoriatic arthritis; synovitis; mening
  • the improvement of intestinal health may be helpful for beneficial proliferation and suppression of harmful bacteria in the intestine, help for intestinal health by regulating immunity, or help for bowel movement.
  • antimicrobial agent is intended to (i) inhibit, reduce, or prevent the growth of bacteria; (ii) inhibit or reduce the ability of the bacteria to cause an infection in a subject; or (iii) a substance capable of inhibiting or reducing the ability of bacteria to proliferate or remain infectious in the environment.
  • the bacterial infections may include infections caused by gram-positive bacteria or gram-negative bacteria.
  • the bacterial infection is Clostridioides , Helicobacter, Escherichia , Salmonella , Staphylococcus , Streptococcus , Haemophilus ( Haemophilus ), Klebsiella , Moraxella , Enterobacter , Proteus , Serratia , Pseudomonas , Acinetobacter , Citrobacter ( Citrobacter ), Stenotrophomonas , Bacteroides , Prevotella , Fusobacterium, and Fusobacterium .
  • the bacterial infection is Clostridioides difficile infection (CDI), or Clostridioides difficile associated disease (CDAD: Clostridioides difficile associated disease), for example, Clostridioides difficile associated diarrhea ( Clostridioides difficile associated diarrhea).
  • CDI Clostridioides difficile infection
  • CDAD Clostridioides difficile associated disease
  • the composition is 0.00001 wt% to 80 wt%, for example, 0.00001 wt% to 60 wt%, 0.00001 wt% to 40 wt%, 0.00001 wt% to 30 wt%, 0.00001 wt% to 20 wt%, based on the total weight of the composition.
  • % 0.00001% to 10%, 0.00001% to 5%, 0.05% to 60%, 0.05% to 40%, 0.05% to 30%, 0.05% to 20%, 0.05% to 10% by weight, 0.05% to 5% by weight, 0.1% to 60% by weight, 0.1% to 40% by weight, 0.1% to 30% by weight, 0.1% to 20% by weight, 0.1% by weight % to 10% by weight, or 0.1% to 5% by weight of a strain, a lysate thereof, a culture medium, or an extract of a culture medium thereof.
  • the term "included as an active ingredient” means that the strain of the present specification, the endoplasmic reticulum derived from the strain, the lysate of the strain, the culture medium, or an extract of its culture medium is added to the extent that the above-mentioned effect can be exhibited, It means that it is formulated in various forms by adding various components as subcomponents for drug delivery and stabilization.
  • the composition can be a pharmaceutical composition.
  • Types of pharmaceutically active ingredients capable of delivering the active ingredient into the subject include anticancer agents, contrast agents (dye), hormones, anti-hormonal agents, vitamins, calcium agents, mineral preparations, saccharide preparations, organic acid preparations, protein amino acid preparations, detoxifying agents, and enzymes.
  • Preparations metabolic preparations, diabetes concomitant medicines, tissue regeneration medicines, chlorophyll preparations, pigment preparations, tumor medicines, tumor treatment agents, radiopharmaceuticals, tissue cell diagnostic agents, tissue cell therapy agents, antibiotics preparations, antiviral agents, complex antibiotics preparations, chemicals Therapeutic agents, vaccines, toxins, toxoids, antitoxins, leptospira serum, blood products, biological agents, analgesics, immunogenic molecules, antihistamines, allergy medications, non-specific immunogenic agents, anesthetics, stimulants, psychoactive agents, small molecule compounds, nucleic acids, It may include aptamers, antisense nucleic acids, oligonucleotides, peptides, siRNAs, and micro RNAs.
  • the pharmaceutical composition may additionally include a pharmaceutically acceptable diluent or carrier.
  • the diluent may be lactose, corn starch, soybean oil, microcrystalline cellulose, or mannitol, and magnesium stearate, talc, or a combination thereof as a lubricant.
  • the carrier may be an excipient, a disintegrant, a binder, a lubricant, or a combination thereof.
  • the excipient may be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof.
  • the disintegrant may be calcium carboxymethylcellulose, sodium starch glycolate, calcium monohydrogen phosphate, or a combination thereof.
  • the binder may be polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, or a combination thereof.
  • the lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof.
  • Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories.
  • Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.
  • Witepsol, Macrogol, Tween 61, cacao butter, liurine fat, glycerogeratin and the like may be used as a base for the suppository.
  • the pharmaceutical composition may include carbohydrates such as glucose, sucrose or dextran, antioxidants such as ascorbic acid or glutathione, chelating agents, and low molecular weight proteins in order to increase stability or absorption.
  • carbohydrates such as glucose, sucrose or dextran
  • antioxidants such as ascorbic acid or glutathione
  • chelating agents such as ascorbic acid or glutathione
  • low molecular weight proteins such as ascorbic acid or glutathione
  • other stabilizers may be used as pharmaceuticals.
  • the pharmaceutical composition may be formulated for oral or parenteral administration.
  • Oral dosage forms may be granules, powders, solutions, tablets, capsules, dry syrups, or combinations thereof.
  • Parenteral dosage forms may be injections.
  • the composition may be a health functional food composition.
  • the health functional food composition may be used alone or in combination with the strain or its culture medium or other food or food component, and may be appropriately used according to a conventional method.
  • the mixing amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment).
  • the composition of the present specification may be added in an amount of 15 parts by weight or less based on the raw material.
  • beverage compositions may contain various flavoring agents or natural carbohydrates as additional components, like conventional beverages.
  • the natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • sweetener natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame may be used.
  • the health food composition may also contain nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, and carbonated beverages. carbonation agent used, or a combination thereof.
  • the health functional food composition may also contain natural fruit juice, fruit juice beverages, fruit flesh for preparing vegetable beverages, or a combination thereof.
  • the composition may be a cosmetic composition.
  • the cosmetic composition may have, for example, softening lotion, nutrient lotion, massage cream, nutrient cream, essence, pack, gel, ampoule, or skin-adhesive cosmetic formulation.
  • ingredients included in the cosmetic composition may include ingredients commonly used in cosmetic compositions other than the composition as active ingredients, for example, conventional adjuvants and carriers such as stabilizers, solubilizers, vitamins, pigments and flavors. can include
  • composition may be a composition for external application for skin.
  • the external skin preparation may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal delivery patch, drug-containing bandage, lotion, or a combination thereof.
  • the external skin preparation is a component usually used in external preparations for skin such as cosmetics or pharmaceuticals, for example, water-based components, oil-based components, powder components, alcohols, moisturizers, thickeners, ultraviolet absorbers, whitening agents, preservatives, antioxidants, surfactants, and fragrances. , colorants, various skin nutrients, or combinations thereof and may be suitably blended as needed.
  • the external skin preparations include metal sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, bellapamil, licorice extract, glabridin, and calin.
  • Hot-water extracts of fruits, various herbal medicines, tocopherol acetate, glycyrrhizic acid, tranexamic acid and its derivatives or salts and other drugs, vitamin C, magnesium ascorbate phosphate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, Sugars, such as trehalose, etc. can also be mix
  • Another aspect also provides a method of preventing, ameliorating, or treating a condition in a subject comprising treating or administering to a subject in need thereof an effective amount of a composition described above.
  • the condition of the subject may be a condition related to inflammation or a condition related to bacterial infection.
  • Administration may be administered by a method known in the art.
  • Administration can be administered directly to a subject by any means, for example, by routes such as intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal or subcutaneous administration.
  • routes such as intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal or subcutaneous administration.
  • the administration may be administered systemically or locally.
  • the subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat.
  • the subject may be an individual in need of an improvement effect of a condition related to inflammation or a condition related to bacterial infection.
  • the administration is 0.00001 mg to 1,000 mg, for example, 0.00001 mg to 500 mg, 0.00001 mg to 100 mg, 0.00001 mg to 50 mg, 0.00001 mg to 25 mg, 1 mg to 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg, 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg may be administered.
  • the dosage may be prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate and reaction sensitivity, and those skilled in the art can Dosage can be appropriately adjusted in consideration of these factors.
  • the number of administrations can be once a day or twice or more within the range of clinically acceptable side effects, and the administration site can be administered to one or more than two sites, daily or every 2 to 5 days, total
  • the number of administration days may be administered from 1 day to 30 days per treatment. If necessary, the same treatment can be repeated after a titration period.
  • the same dosage per kg as for humans is used, or the above dosage is converted by the volume ratio (eg, average value) of the organ (heart, etc.) between the target animal and the human.
  • a single dose can be administered.
  • novel strain and the endoplasmic reticulum derived from the novel strain there is an effect that can be usefully used for the prevention, improvement, or treatment of inflammation-related conditions or bacterial infections.
  • N negative control
  • P untreated control
  • EV endoplasmic reticulum of Example 2.
  • Figure 2 is a graph showing the protein expression of pro-inflammatory cytokines (TNF, IL-6 and CCL2) and anti-inflammatory cytokines (IL-10) in cell processing of the endoplasmic reticulum of the strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • N negative control
  • P untreated control
  • EV endoplasmic reticulum of Example 2.
  • Figure 3 is a graph showing the cytotoxicity results of the endoplasmic reticulum of the strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • Figure 4 is a graph showing the cytotoxicity results when the endoplasmic reticulum of the strain and the endoplasmic reticulum of Clostridioides difficile were treated together according to one embodiment; CdEV: endoplasmic reticulum of Clostridioides difficile, BBH024: endoplasmic reticulum of Example 1 strain, Type strain: endoplasmic reticulum of Roseburia paesis standard strain.
  • Figure 5 is a graph showing the reduction activity of inflammation induced by Clostridioides difficile of the endoplasmic reticulum of the strain according to one embodiment
  • CdEV endoplasmic reticulum of Clostridioides difficile
  • BBH024 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Roseburia paesis standard strain.
  • Figure 6 is a graph showing the protein expression of pro-inflammatory cytokines (TNF and CCL2) and anti-inflammatory cytokines (IL-6 and IL-10) in cell processing of the endoplasmic reticulum of the strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • N negative control
  • P untreated control
  • EV endoplasmic reticulum of Example 2.
  • Figure 7 is a graph showing the cytotoxicity results of the endoplasmic reticulum of the strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • Figure 8 is a graph showing the cytotoxicity results when the endoplasmic reticulum and Clostridioides difficile toxin B of a strain according to one embodiment are treated together;
  • C. difficile toxin B Clostridioides difficile toxin B
  • BBH026 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Clostridium reptum standard strain.
  • Figure 9 is a graph showing the reduction activity of inflammation induced by Clostridioides difficile of the endoplasmic reticulum of the strain according to one embodiment
  • C. difficile toxin B Clostridioides difficile toxin B
  • BBH026 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Clostridium reptum standard strain.
  • Figure 10 is a graph showing the amount of nitric oxide produced according to the cell treatment of the endoplasmic reticulum of the strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • Figure 11 is a graph showing the protein expression of pro-inflammatory cytokines (TNF and CCL2) and anti-inflammatory cytokines (IL-6 and IL-10) in cell processing of the endoplasmic reticulum of a strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • N negative control
  • P untreated control
  • EV endoplasmic reticulum of Example 2.
  • Figure 12 is a graph showing the cytotoxicity results of the endoplasmic reticulum of the strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • Figure 13 is a graph showing the cytotoxicity results when the endoplasmic reticulum and Clostridioides difficile toxin B of a strain according to one embodiment are treated together;
  • C. difficile toxin B Clostridioides difficile toxin B
  • BBH027 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Coprococcus eulactus standard strain.
  • Figure 14 is a graph showing the reduction activity of inflammation induced by Clostridioides difficile of the endoplasmic reticulum of a strain according to one embodiment;
  • C. difficile toxin B Clostridioides difficile toxin B, BBH027: endoplasmic reticulum of Example 1 strain, Type strain: endoplasmic reticulum of Coprococcus eulactus standard strain.
  • Figure 15 is a graph showing the amount of nitric oxide produced according to the cell treatment of the endoplasmic reticulum of the strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • Figure 16 is a graph showing the protein expression of pro-inflammatory cytokines (TNF, IL-6 and CCL2) and anti-inflammatory cytokines (IL-10) in cell processing of the endoplasmic reticulum of the strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • N negative control
  • P untreated control
  • EV endoplasmic reticulum of Example 2.
  • FIG. 17 is a graph showing the culture rate of C.difficile in a culture medium of a strain according to one embodiment
  • C. difficile Clostridioides difficile
  • A. butyriciproducens BBH028 culture medium of Example 1 strain
  • A. butyriciproducens (T) culture medium of Agatobaculum butyriciproducens standard strain.
  • 18 is a graph showing the culture rate of C. difficile in the endoplasmic reticulum of a strain according to one embodiment.
  • Figure 19 is a graph showing the cytotoxicity results of the endoplasmic reticulum of the strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • Figure 20 is a graph showing the cytotoxicity results when the endoplasmic reticulum and Clostridioides difficile toxin B of a strain according to one embodiment are treated together;
  • C. difficile toxin B Clostridioides difficile toxin B
  • BBH028 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Agatobaculum butyriciproducens standard strain.
  • Figure 21 is a graph showing the reduction activity of inflammation induced by Clostridioides difficile of the endoplasmic reticulum of a strain according to one embodiment
  • C. difficile toxin B Clostridioides difficile toxin B
  • BBH028 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Agatobaculum butyriciproducens standard strain.
  • feces collected from a healthy person and 10 ml of 1 x PBS (Phosphate buffer saline) were mixed and vortexed to suspend the feces. Then, it was filtered with a cell strainer to remove undigested food and small particulate matter.
  • the filtered fecal suspension is serially diluted and spread to FAB (Fastidious Anaerobe Broth) or BHIs (Brain Heart Infusion-supplemented) + 5% Sheep blood medium Plate or 0.2% Mucin medium Plate at 10 -6 ⁇ 10 -8 After culturing at 37 ° C for more than 3 days, bacteria were selected.
  • FAB Fredious Anaerobe Broth
  • BHIs Brain Heart Infusion-supplemented
  • PCR amplification was performed on the cultured colony, and the nucleotide sequence of the 16S rRNA region determined among the isolated and cultured microbial colonies was transferred to other cultures registered with the BLAST program provided on the website of the National Center for Biotechnology Information (NCBI). The strains were compared and analyzed.
  • Roseburia faecis BBH 024 with 99% homology was isolated.
  • the selected Roseburia faecis BBH 024 strain was deposited with the Korea Center for Biological Resources on May 25, 2021 and was given accession number KCTC14582BP, and the Roseburia faecis BBH 024 strain has a 16S rRNA sequence of SEQ ID NO: 1 (complementary DNA).
  • Clostridium leptum BBH 026 with 99% homology was isolated.
  • the selected Clostridium leptum BBH 026 strain was deposited with the Korea Center for Biological Resources on October 1, 2021 and was given accession number KCTC14721BP, and the Clostridium leptum BBH 026 strain has a 16s rRNA sequence of SEQ ID NO: 2 (complementary DNA).
  • Coprococcus eutactus BBH 027 with 99% homology was isolated.
  • the selected Coprococcus eutactus BBH 027 strain was deposited with the Korea Center for Biological Resources on October 1, 2021 and was given accession number KCTC14722BP, and the Coprococcus eutactus BBH 027 strain has a 16s rRNA sequence of SEQ ID NO: 3 (complementary DNA).
  • Agathobaculum butyriciproducens BBH 028 with 99% homology was isolated.
  • the selected Agathobaculum butyriciproducens BBH 028 strain was deposited with the Korea Center for Biological Resources on October 1, 2021 and assigned accession number KCTC14723BP, and the Agathobaculum butyriciproducens BBH 028 strain has a 16S rRNA sequence of SEQ ID NO: 4 (complementary DNA).
  • the endoplasmic reticulum of the strain isolated in the above example was isolated.
  • the isolated strain was cultured in BHIs broth, PY+X broth, or PYG broth (DSMZ 104) at 37° C. under anaerobic conditions for 2 or 3 days. Thereafter, the culture solution was centrifuged at 5000 x g for 20 minutes to remove bacterial debris.
  • the anti-inflammatory activity of the endoplasmic reticulum of the strain isolated in Example 2 was analyzed.
  • Mouse macrophage Raw264.7 cells were cultured in Dulbecco Modified Eagle Medium (DMEM) containing 10% fetal bovine serum (FBS) and 1% antibiotics (100 U/mL penicillin and 100 ⁇ g/mL streptomycin) for 5 It was incubated at 37°C in the presence of % CO 2 . Thereafter, the Raw 264.7 cells were dispensed into a 48-well plate at a concentration of 5 ⁇ 10 4 cells/well by 300 ⁇ L, and cultured in a CO 2 incubator at 37° C. for 24 hours.
  • DMEM Dulbecco Modified Eagle Medium
  • FBS fetal bovine serum
  • antibiotics 100 U/mL penicillin and 100 ⁇ g/mL streptomycin
  • LPS lipopolysaccharide
  • 1, 10 and 15 are graphs showing the amount of nitric oxide produced according to cell treatment of the endoplasmic reticulum of a strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • the endoplasmic reticulum of the strain significantly reduced the amount of NO production of the inflammatory cells compared to the untreated control group.
  • pro-inflammatory cytokine inhibitory activity and anti-inflammatory cytokine promoting activity of the endoplasmic reticulum of the strain were measured. Specifically, in the same manner as above, LPS-treated Raw264.7 cells were treated with the endoplasmic reticulum at a concentration of 0.01, 1, 10 or 100 ⁇ g/ml, and then incubated at 37° C. for 16 hours. Thereafter, the protein expression of TNF, IL-6 and CCL2, which are pro-inflammatory cytokines, and the protein expression of IL-10, which is an anti-inflammatory cytokine, were measured in the cells using an ELISA kit (BD bioscience, USA) according to the manufacturer's instructions. Absorbance was measured at 450 nm, and the results are shown in FIGS. 2, 6, 11 and 16 for each strain, respectively.
  • Figures 2, 6, 11 and 16 are graphs showing the protein expression of pro-inflammatory cytokines and anti-inflammatory cytokines in cell processing of the endoplasmic reticulum of a strain according to one embodiment; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
  • the endoplasmic reticulum of the strain significantly reduced pro-inflammatory cytokines compared to the untreated control group and significantly increased anti-inflammatory cytokines compared to the untreated control group.
  • strain according to one embodiment can be usefully used for preventing, improving, or treating inflammatory diseases, particularly inflammatory bowel disease or irritable bowel syndrome.
  • Example 1 The antibacterial activity of the strain isolated in Example 1 was analyzed.
  • the strain of Example 1 was pre-cultured in PYG broth, adjusted to an OD of 0.1, and then added to PYG broth. After inoculation at a rate of 1%, it was cultured under anaerobic conditions at 37°C for 48 hours, and the C.difficile strain was cultured in RCM (Reinforced clostridial medium) broth. The cultured strain of Example 1 was centrifuged at 5000 xg for 20 minutes to separate the pellet and the supernatant, and the pellet was washed twice with PBS, resuspended, and adjusted to an OD of 0.5, respectively.
  • RCM Reinforced clostridial medium
  • the endoplasmic reticulum was isolated by the method of Example 2.
  • C.difficile was cultured in PYG broth for 48 hours, adjusted to OD 0.5, and then inoculated with C.difficile at a ratio of 10% to the endoplasmic reticulum of the strain of the above example, and then cultured under anaerobic conditions for 1 day. Afterwards, the culture rate of C. difficile was measured spectrophotometrically. The analysis results are shown in FIG. 18 .
  • FIG. 17 is a graph showing the culture rate of C.difficile in a culture medium of a strain according to one embodiment
  • C. difficile Clostridioides difficile
  • A. butyriciproducens BBH028 culture medium of Example 1 strain
  • A. butyriciproducens (T) culture medium of Agatobaculum butyriciproducens standard strain.
  • 18 is a graph showing the culture rate of C. difficile in the endoplasmic reticulum of a strain according to one embodiment.
  • the strain according to one embodiment and/or the endoplasmic reticulum derived therefrom has antibacterial activity against bacteria, for example, Gram-negative bacteria.
  • these results show that the strain and/or its derived endoplasmic reticulum according to one embodiment is useful for preventing, improving, or treating Clostridioides difficile infection (CDI), or irritable bowel syndrome resulting therefrom. means that it can be used
  • N negative control
  • P untreated control
  • EV endoplasmic reticulum of Example 2.
  • mice macrophage Raw264.7 cells were treated with Clostridioides difficile endoplasmic reticulum (CdEV) 100 gu/ml or Clostridioides difficile toxin B ( C. difficile toxin B) 100 After treatment with ⁇ g/ml, the cells were incubated for 4 hours at 37°C.
  • CdEV Clostridioides difficile endoplasmic reticulum
  • Roseburia phaecsis standard strain (KCTC15739), Clostridium reptum standard strain (KCTC25281), Coprococcus Eulactus standard strain (ATCC27759) or Agatobaculum butyriciproducens standard strain (KCTC15532)
  • KCTC15739 Clostridium reptum standard strain
  • KCTC25281 Clostridium reptum standard strain
  • Coprococcus Eulactus standard strain ATCC27759
  • Agatobaculum butyriciproducens standard strain (KCTC15532)
  • the endoplasmic reticulum of each strain of Example 1 was treated with an amount of 0.01, 1, 10 or 100 ⁇ g/ml, and then cultured at 37° C. for 16 hours, and the cell viability was measured in the same manner as in Experimental Example 3. The results are shown in Figures 4, 8, 13 and 20 for each strain, respectively.
  • the relative concentrations of pro-inflammatory cytokines TNF, IL-6, and CCL2, and anti-inflammatory cytokines IL-10 in the cells were measured by absorbance at 450 nm using an ELISA kit (BD bioscience, USA) according to the manufacturer's instructions. was measured, and the results are shown in FIGS. 5, 9, 14 and 21 for each strain, respectively.
  • Figure 4 is a graph showing the cytotoxicity results when the endoplasmic reticulum of the strain and the endoplasmic reticulum of Clostridioides difficile were treated together according to one embodiment; CdEV: endoplasmic reticulum of Clostridioides difficile, BBH024: endoplasmic reticulum of Example 1 strain, Type strain: endoplasmic reticulum of Roseburia paesis standard strain.
  • Figure 8 is a graph showing the cytotoxicity results when the endoplasmic reticulum and Clostridioides difficile toxin B of a strain according to one embodiment are treated together;
  • C. difficile toxin B Clostridioides difficile toxin B
  • BBH026 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Clostridium reptum standard strain.
  • Figure 13 is a graph showing the cytotoxicity results when the endoplasmic reticulum and Clostridioides difficile toxin B of a strain according to one embodiment are treated together;
  • C. difficile toxin B Clostridioides difficile toxin B
  • BBH027 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Coprococcus eulactus standard strain.
  • Figure 20 is a graph showing the cytotoxicity results when the endoplasmic reticulum and Clostridioides difficile toxin B of a strain according to one embodiment are treated together;
  • C. difficile toxin B Clostridioides difficile toxin B
  • BBH028 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Agatobaculum butyriciproducens standard strain.
  • Figure 5 is a graph showing the reduction activity of inflammation induced by Clostridioides difficile of the endoplasmic reticulum of the strain according to one embodiment
  • CdEV endoplasmic reticulum of Clostridioides difficile
  • BBH024 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Roseburia paesis standard strain.
  • Figure 9 is a graph showing the reduction activity of inflammation induced by Clostridioides difficile of the endoplasmic reticulum of the strain according to one embodiment
  • C. difficile toxin B Clostridioides difficile toxin B
  • BBH026 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Clostridium reptum standard strain.
  • Figure 14 is a graph showing the reduction activity of inflammation induced by Clostridioides difficile of the endoplasmic reticulum of a strain according to one embodiment;
  • C. difficile toxin B Clostridioides difficile toxin B, BBH027: endoplasmic reticulum of Example 1 strain, Type strain: endoplasmic reticulum of Coprococcus eulactus standard strain.
  • Figure 21 is a graph showing the reduction activity of inflammation induced by Clostridioides difficile of the endoplasmic reticulum of a strain according to one embodiment
  • C. difficile toxin B Clostridioides difficile toxin B
  • BBH028 endoplasmic reticulum of Example 1 strain
  • Type strain endoplasmic reticulum of Agatobaculum butyriciproducens standard strain.
  • the endoplasmic reticulum of the strain is increased by the endoplasmic reticulum of Clostridioides difficile or Clostridioides difficile toxin B. It was found that the amounts of the kines TNF, IL-6 and CCL2 were significantly reduced compared to the standard strain, and the amount of the anti-inflammatory cytokine IL-10 reduced by Clostridioides difficile toxin B was significantly increased compared to the standard strain. could In particular, it was confirmed that the standard strain showed little effect of reducing TNF, IL-6 and CCL2, and increasing IL-10.
  • strain according to one embodiment and/or the endoplasmic reticulum derived therefrom have significant anti-inflammatory activity, preventing, improving, Or it means that it can be usefully used for treatment.

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Abstract

La présente invention concerne un nouveau microorganisme, un lysat associé, une culture associée, un extrait de la culture, des vésicules associées et des utilisations anti-inflammatoires et/ou antibactériennes associées. Une nouvelle souche et les vésicules dérivées de celle-ci, selon un aspect, peuvent être utilisées efficacement dans la prévention, le soulagement ou le traitement d'affections liées à une inflammation ou d'infections bactériennes.
PCT/KR2022/016596 2021-10-27 2022-10-27 Nouvelle souche bactérienne, vésicules dérivées de celle-ci, et utilisation anti-inflammatoire et anti-bactérienne associées WO2023075458A1 (fr)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
KR1020210144399A KR102337993B1 (ko) 2021-10-27 2021-10-27 클로스트리디움 렙텀 균주, 및 그의 유래의 소포체 및 그의 항염증 및 항균 용도
KR1020210144400A KR102337991B1 (ko) 2021-10-27 2021-10-27 코프로코커스 유탁터스 균주, 및 그의 유래의 소포체 및 그의 항염증 및 항균 용도
KR10-2021-0144399 2021-10-27
KR10-2021-0144400 2021-10-27
KR1020210149529A KR102337998B1 (ko) 2021-11-03 2021-11-03 로제부리아 파에시스 균주, 및 그의 유래의 소포체 및 그의 항염증 및 항균 용도
KR10-2021-0149529 2021-11-03
KR10-2021-0153854 2021-11-10
KR1020210153854A KR102337995B1 (ko) 2021-11-10 2021-11-10 아가토바쿨룸 부티리시프로두켄스 균주, 및 그의 유래의 소포체 및 그의 항염증 및 항균 용도

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KR20180012849A (ko) * 2015-06-15 2018-02-06 4디 파마 리서치 리미티드 박테리아 균주를 함유한 조성물
KR20190030687A (ko) * 2016-06-14 2019-03-22 베단타 바이오사이언시즈, 인크. 클로스트리디움 디피실레 감염의 치료
US20190247445A1 (en) * 2016-07-01 2019-08-15 Regents Of The University Of Minnesota Compositions and methods for c. difficile treatment
KR20200053531A (ko) * 2017-09-08 2020-05-18 에벨로 바이오사이언시즈, 인크. 박테리아 세포외 소포
US20200405775A1 (en) * 2017-12-11 2020-12-31 Vedanta Biosciences, Inc Compositions and methods for suppressing pathogenic organisms
WO2021016081A1 (fr) * 2019-07-19 2021-01-28 Finch Therapeutics Holdings Llc. Méthodes et produits destinés au traitement de troubles gastro-intestinaux
KR102337998B1 (ko) * 2021-11-03 2021-12-14 주식회사 바이오뱅크힐링 로제부리아 파에시스 균주, 및 그의 유래의 소포체 및 그의 항염증 및 항균 용도

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20180012849A (ko) * 2015-06-15 2018-02-06 4디 파마 리서치 리미티드 박테리아 균주를 함유한 조성물
KR20190030687A (ko) * 2016-06-14 2019-03-22 베단타 바이오사이언시즈, 인크. 클로스트리디움 디피실레 감염의 치료
US20190247445A1 (en) * 2016-07-01 2019-08-15 Regents Of The University Of Minnesota Compositions and methods for c. difficile treatment
KR20200053531A (ko) * 2017-09-08 2020-05-18 에벨로 바이오사이언시즈, 인크. 박테리아 세포외 소포
US20200405775A1 (en) * 2017-12-11 2020-12-31 Vedanta Biosciences, Inc Compositions and methods for suppressing pathogenic organisms
WO2021016081A1 (fr) * 2019-07-19 2021-01-28 Finch Therapeutics Holdings Llc. Méthodes et produits destinés au traitement de troubles gastro-intestinaux
KR102337998B1 (ko) * 2021-11-03 2021-12-14 주식회사 바이오뱅크힐링 로제부리아 파에시스 균주, 및 그의 유래의 소포체 및 그의 항염증 및 항균 용도

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