WO2017026620A1 - Composition pour prévenir, soulager ou traiter des maladies immunes médiées par th1, th17 ou th2, la composition contenant, comme principe actif, lactobacillus pentosus - Google Patents

Composition pour prévenir, soulager ou traiter des maladies immunes médiées par th1, th17 ou th2, la composition contenant, comme principe actif, lactobacillus pentosus Download PDF

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WO2017026620A1
WO2017026620A1 PCT/KR2016/003202 KR2016003202W WO2017026620A1 WO 2017026620 A1 WO2017026620 A1 WO 2017026620A1 KR 2016003202 W KR2016003202 W KR 2016003202W WO 2017026620 A1 WO2017026620 A1 WO 2017026620A1
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mediated immune
strain
composition
immune disease
lactobacillus pentosus
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PCT/KR2016/003202
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Korean (ko)
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이소영
손동화
신희순
임성일
도정룡
배민정
박소림
엄지은
남영도
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한국식품연구원
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Priority claimed from KR1020160026193A external-priority patent/KR101761506B1/ko
Application filed by 한국식품연구원 filed Critical 한국식품연구원
Publication of WO2017026620A1 publication Critical patent/WO2017026620A1/fr

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135Bacteria or derivatives thereof, e.g. probiotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66Microorganisms or materials therefrom
    • A61K35/74Bacteria
    • A61K35/741Probiotics
    • A61K35/744Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747Lactobacilli, e.g. L. acidophilus or L. brevis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00Microorganisms, 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
    • C12N1/20Bacteria; Culture media therefor
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00Microorganisms, 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
    • C12N1/20Bacteria; Culture media therefor
    • C12N1/205Bacterial isolates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12RINDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00Microorganisms ; Processes using microorganisms
    • C12R2001/01Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/225Lactobacillus

Definitions

  • the present invention provides a novel Lactobacillus pentosus KF340 strain (Accession No. KCCM 11675P) and Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease comprising the strain as an active ingredient. , To improve or treat compositions.
  • the metagenome project which identifies the intestinal flora of the intestinal bacteria, mainly in the United States, reveals the relationship between the distribution of intestinal flora and various immune system diseases including allergies. As a result, the distribution and diversity of intestinal bacteria and intestinal immunity and the immune system are closely related.
  • the global probiotics market is estimated at KRW35 trillion in 2014, and is expected to grow at an annual average rate of 7.6% to KRW 57 trillion by 2020.
  • the domestic probiotics market is small in size, with KRW 150 billion as of 2014, but the market is growing rapidly with 250% growth compared to 2013.
  • probiotics are derived from human intestines or foods, there is an advantage that there is no big problem in the demonstration of stability with other chemical agents if the efficacy using animal models is proven.
  • efficacy of probiotics as an immunomodulator has been verified through various clinical trials, and many diseases such as asthma, ulcerative colitis, and arthritis have been tried. Recently, clinical trials and studies on atopy have been accelerated. There is a situation.
  • VSL3 # was developed by VSL Pharmaceutical company in Canada, and is currently active in the global market, and recently, it is also sold in the domestic market as an individual immunomodulator.
  • the present inventors have made intensive research efforts to develop probiotics for preventing or treating allergic and inflammatory diseases caused by Th1, Th17, or Th2 immune responses.
  • a novel Lactobacillus pentosus strain having anti-allergic and anti-inflammatory activity was selected from kimchi, a traditional fermented food, and when the strain was treated, regulatory T cell induction, regulatory B cell induction, and immune activity.
  • IL-10 immune tolerant cytokines
  • IL-12 cytokines
  • IgE immunoglobulin E
  • Th1-related cytokines Th17-related cytokines
  • the present invention was completed by confirming that allergic and inflammation are effectively controlled by inhibition of the production of Caine, and Th2-related cytokines, and enhanced intestinal immune response.
  • the present invention provides a Lactobacillus pentosus KF340 strain (Accession No. KCCM 11675P) having a prophylactic, ameliorating, or therapeutic activity for Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease. It aims to provide.
  • the present invention comprises the Lactobacillus pentosus KF340 strain (Accession No. KCCM 11675P) as an active ingredient, prevention of Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease, It is another object to provide a composition for improvement or treatment.
  • the present invention is a novel Lactobacillus ( Lactobacillus) having a prophylactic, ameliorating or therapeutic activity of Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease.
  • pentosus ) KF340 strain (Accession No. KCCM 11675P) is provided.
  • the present invention includes the Lactobacillus pentosus KF340 strain (Accession No. KCCM 11675P) as an active ingredient, preventing, ameliorating, or treating Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease. It provides a composition for.
  • the strain is characterized in that it is isolated from kimchi.
  • the strain may be live or dead.
  • the composition may induce regulatory T cells.
  • the composition may induce regulatory B cells.
  • the composition may allow the ratio of interleukin-10 (IL-10) production to interleukin-12 (IL-12) production to be 5-30.
  • IL-10 interleukin-10
  • IL-12 interleukin-12
  • the composition may inhibit the production of immunoglobulin E (IgE).
  • IgE immunoglobulin E
  • the composition may inhibit Th1, Th17, or Th2 related cytokine production.
  • the composition may enhance intestinal immune response.
  • the Th1-mediated immune disease or Th17-mediated immune disease may be transplant rejection, autoimmune disease, or inflammatory disease.
  • the Th2-mediated immune disease may be an allergic disease.
  • the allergic diseases include food allergies, bronchial asthma, allergic rhinitis (acute or chronic), atopic dermatitis, allergic conjunctivitis, allergic otitis media, urticaria and anaphylactic shock, contact hypersensitivity, allergic contact dermatitis, Bacterial allergies, fungal allergies, viral allergies, drug allergies, thyroid and allergic encephalitis.
  • the composition may be a pharmaceutical, food, nutraceutical, cosmetics, or feed composition.
  • the present invention comprises administering to a subject a composition comprising a Lactobacillus pentosus KF340 strain (Accession No. KCCM 11675P) as an active ingredient, a Th1-mediated immune disease, a Th17-mediated immune disease, or a Th2-mediated disease
  • a composition comprising a Lactobacillus pentosus KF340 strain (Accession No. KCCM 11675P) as an active ingredient, a Th1-mediated immune disease, a Th17-mediated immune disease, or a Th2-mediated disease
  • a method for preventing or treating an immune disease is provided.
  • the present invention also provides a prophylactic or therapeutic use of a Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease of a composition comprising Lactobacillus pentosus KF340 strain (Accession No. KCCM 11675P) as an active ingredient. do.
  • the novel Lactobacillus pentosus KF340 strain (Accession No. KCCM 11675P) according to the present invention is immune tolerant cytokine (IL-10; anti-inflammatory) for regulatory T cells and regulatory B cell induction, immune active cytokines (IL-12).
  • IL-10 immune tolerant cytokine
  • IL-12 immune active cytokines
  • Cytokine ratio inhibition of immunoglobulin E (IgE) production, inhibition of Th1-related cytokines, Th17-related cytokines, and Th2-related cytokines during immune hypersensitivity, and enhanced intestinal immune response following IgA secretion
  • IgE immunoglobulin E
  • Th1-related cytokines Th17-related cytokines
  • Th2-mediated autoimmune diseases more preferably allergic or inflammatory diseases. It is expected to be able.
  • 1 is a result of measuring the expression change of Foxp3 according to the co-culture of Lactobacillus pentosus KF340 strain and immune cells.
  • FIG. 2A to 2D show the effects of atopic dermatitis improvement following oral administration of Lactobacillus pentosus KF340 strain in mice with atopic dermatitis
  • FIG. 2A shows ear thickness changes
  • FIG. 2B shows erythema, keratin, and edema
  • 2C is a photograph of a mouse ear which is an atopic dermatitis lesion site
  • FIG. 2D is a result of observing epithelial cell thickness and inflammatory cell infiltration by H & E or TB staining of the lesion site.
  • Figure 3a is a result of measuring the IL-4 secretion from lymphocytes isolated from each lymph node of mice after oral administration of Lactobacillus pentosus KF340 strain in mice with atopic dermatitis (PP: Payer's patch, mLN: mesenteric lymph nodes, dLN: draining lymph node),
  • Figure 3b is the result of measuring the expression of GATA-3, a transcription factor of Th2 in the lesion tissue.
  • Figures 4a to 4d is a result showing the effect of atopic dermatitis improved by oral administration of live or dead Lactobacillus pentosus KF340 in mice induced atopic dermatitis
  • Figure 4a is a result of measuring the change in ear thickness
  • Figure 4b Figure 4c is a photograph of the mouse ear, atopic dermatitis lesion site, the result of measuring the amount of IL-17A secreted by Th17 (PBS: control, 340: live, HK340: dead)
  • Figure 4d is Th17-related transcription It is the result of measuring the expression of ROR ⁇ t which is a factor.
  • Figure 5a is a result showing the increase in IL-10 secretion by Lactobacillus pentosus KF340 strain in splenocytes
  • Figure 5b is a result showing the increase of B cell activity in the spleen by the strain treatment
  • Figure 5c is B220 + CD5 + CD1d + B10 cell population increase by strain treatment.
  • Figure 6 is the result of measuring the expression change of B220 + CD5 + CD1d + by administration of Lactobacillus pentosus KF340 strain in atopic dermatitis mouse model (SPL: spleen, PP: Payer's patch).
  • Figure 7 shows the results of increasing the frequency of dendritic cells (DC) in the Payer's patch, increased CD80 and CD86 expression of dendritic cells after administration of Lactobacillus pentosus KF340 strain in atopic dermatitis mouse model.
  • DC dendritic cells
  • FIGS. 8a and 8b are to determine the direct effect on the dendritic cells (DC) of the Lactobacillus pentosus KF340 strain
  • Figure 8a is bone marrow dendritic cells (BMDC) after treatment with the strain IL- 10 and TGF- ⁇ mRNA and protein expression was measured
  • Figure 8b is a result of measuring the BAFF mRNA expression in dendritic cells (DC) or Payer's patch.
  • Figure 9a is a result of measuring the amount of IgA by recovering the mouse feces before the administration of Lactobacillus pentosus KF340 strain (0W) and the end of the experiment (8W) after administration to atopic dermatitis
  • Figure 9b is IL-6 This is the result of measuring the amount of.
  • FIG. 10 is a diagram showing an experimental method and a schedule for producing a food allergic mouse model.
  • FIG. 11A to 11C are results showing food allergic inhibitory activity of the Lactobacillus pentosus KF340 strain, FIG. 11A is a change in rectal temperature, FIG. 11B is a diarrhea response, and FIG. 11C is a result of measuring anaphylaxis.
  • the present inventors have made intensive research efforts to develop probiotics for preventing or treating allergic and inflammatory diseases, diseases or conditions caused by Th1 or Th2 immune responses.
  • a novel Lactobacillus pentosus strain having anti-allergic and anti-inflammatory activity was selected from kimchi, a traditional fermented food, and when the strain was treated, regulatory T cell induction, regulatory B cell induction, and immune activity.
  • IL-10 immune tolerant cytokines
  • IL-12 cytokines
  • IgE immunoglobulin E
  • the present invention provides a novel Lactobacillus pentosus KF340 strain (Accession No. KCCM 11675P) having prophylactic, ameliorating or therapeutic activity for Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease.
  • KCCM 11675P novel Lactobacillus pentosus KF340 strain having prophylactic, ameliorating or therapeutic activity for Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease.
  • the present invention includes the Lactobacillus pentosus ( Lactobacillus pentosus ) KF340 strain (Accession No. KCCM 11675P) as an active ingredient Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease prevention, improvement Or a therapeutic composition.
  • Lactobacillus pentosus Lactobacillus pentosus
  • KF340 strain Accession No. KCCM 11675P
  • Th1-mediated immune disease Th17-mediated immune disease
  • Th2-mediated immune disease prevention improvement Or a therapeutic composition.
  • prevention means any action that inhibits or delays the onset of Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease by administration of a composition according to the present invention. do.
  • the term " improvement" means any action that at least reduces the parameters associated with the condition being treated, such as the extent of symptoms.
  • the composition may be used simultaneously or separately with a medicament for treatment before or after the onset of the disease for the prevention or improvement of Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease. .
  • treatment refers to any action in which symptoms for Th1-mediated immune disease, Th17-mediated immune disease, or Th2-mediated immune disease are ameliorated or beneficially altered by administration of a composition according to the present invention. it means.
  • the term "comprising as an active ingredient” means to include an amount sufficient to achieve the efficacy or activity of the Lactobacillus pentosus KF340 strain. Since the Lactobacillus pentosus KF340 strain of the present invention is a microorganism strain isolated from food, preferably kimchi, there is no side effect on the human body even when the drug is administered in an excessive amount, so that the upper limit of the quantity contained in the composition of the present invention is within the appropriate range. You can choose from.
  • the Lactobacillus pentosus KF340 strain of the present invention is a strain isolated from kimchi, the strain may be live or dead bacteria.
  • the composition of the invention can induce regulatory T cells.
  • the regulatory T cell induction can be confirmed by increasing the expression of Foxp3, a regulatory T cell transcription factor, as demonstrated in the following examples.
  • the composition of the present invention increases the activation of regulatory T cells by 2-20 fold, 5-20 fold, 5-15 fold, 5-10 fold or 7-9 fold as compared to the negative control. It confirmed (refer Example 3).
  • the composition of the invention can induce regulatory B cells.
  • the regulatory B cell induction can be confirmed by increased expression of B220 + CD5 + CD1d + B cells (B10 cells) as demonstrated in the following examples.
  • B10 cells a subset of B cells, are known to have anti-inflammatory cytokine IL-10 production activity and play an important role in regulating inflammatory and autoimmune responses.
  • the Lactobacillus pentosus KF340 strain is induced to induce dendritic cells (DC) of the Payer's patch to be inhibited dendritic cells to promote the production of IL-10 and BAFF, or to the spleen through lymph nodes It was confirmed to migrate to directly induce regulatory B cells (see Example 6).
  • the composition of the present invention increases the activation of regulatory B cells 2-20 fold, 2-10 fold, 2-8 fold, 3-7 fold or 4-6 fold compared to the negative control.
  • the composition of the present invention may increase IL-10 production.
  • IL-10 inhibits macrophage and monocytic (monocyte) and T-cell lymphocyte replication and secretion of inflammatory cytokines (IL-1, TNF- ⁇ , TGF- ⁇ , IL-6, IL-8 and IL-12)
  • IL-1 macrophage and monocytic
  • IL-1, TNF- ⁇ , TGF- ⁇ , IL-6, IL-8 and IL-12 inflammatory cytokine
  • the composition of the present invention may be a ratio of the IL-10 production amount to the IL-12 production amount to 5-30, more preferably the ratio of the IL-10 production amount to the IL-12 production amount is 10-30, 15 It may be -30 or 20-30 (see Example 3-1).
  • the composition of the present invention can inhibit IgE production.
  • IgE is immunoglobulin E, which has affinity for mast cells or basophils and causes an inflammatory reaction when the IgE antibody attached to them reacts with the corresponding antigen (allergen). That is, IgE is an antibody causing anaphylaxis or inflammatory reactions due to allergies. Therefore, it can be seen that allergic reactions or inflammatory reactions are suppressed when IgE production is inhibited.
  • the composition of the present invention may inhibit Th1-related cytokine production. Accordingly, the compositions of the present invention can be used for the prevention, amelioration or treatment of various Th1-mediated immune diseases, diseases or conditions.
  • Th1 cell refers to a subset of helper T cell lymphocytes that are characterized in terms of gene expression, protein secretion and functional activity. For example, Th1 cells exhibit cytokine expression patterns that produce IL-2 and IFN- ⁇ but not IL-4, IL-5, IL-10 and IL-13. Th1 cells are involved in cell-mediated immune responses, organ-specific autoimmune diseases and delayed hypersensitivity to various intracellular pathogens.
  • Th1-mediated immune disease refers to cytokines (Th1-associated cytokines) produced by the production and / or activity of Th1 cells, such as IL-1 ⁇ , IL-2, IL-12, IFN means a disease involving - ⁇ or TNF- ⁇ .
  • the Th1-mediated immune disease may be transplant rejection, autoimmune disease, or inflammatory disease, and more specifically, colitis, inflammatory bowel disease, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, and reactive arthritis.
  • Osteoarthritis Psoriasis, Scleroderma, Osteoporosis, Atherosclerosis, Myocarditis, Endocarditis, Pericarditis, Cystic fibrosis, Hashimoto's thyroiditis, Graves' disease, Leprosy, Syphilis, Lyme disease, Borreliosis, Nervous-Borelliosis, Tuberculosis, Sarcoidosis, Lupus, Discus lupus, Alumnial Lupus, Lupus Nephritis, Systemic Lupus Erythematosus, Asthma, Macular Degeneration, Uveitis, Irritable Bowel Syndrome, Crohn's Disease, Gran Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Chronic Fatigue Fatigue immunodeficiency syndrome, myalgia encephalomyelitis, amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, autism spectrum disorder, attention deficit disorder, and attention deficit Hyper
  • the composition of the present invention may inhibit Th17-associated cytokine production. Accordingly, the compositions of the present invention can be used for the prevention, amelioration or treatment of various Th17-mediated immune diseases, diseases or conditions.
  • Th17 cells refers to a subset of helper T cell lymphocytes that are specified in terms of gene expression, protein secretion, and functional activity. For example, Th17 cells are induced by TGF- ⁇ , IL-6 or IL-21 to produce IL-17, IL-22 and IL-21, but not IL-2, IL-4, IL-5 and IL. -13 indicates a cytokine expression pattern that does not produce. Th17 cells play a direct role in inflammatory and autoimmune pathogenesis and have been reported to induce host defense or aberrant immune responses against pathogens.
  • Th17-mediated immune disease refers to a disease involving cytokines (Th17-associated cytokines), such as IL-17, produced by the production and / or activity of Th17 cells.
  • the Th17-mediated immune disease may specifically be a transplant rejection, an autoimmune disease or an inflammatory disease, and more specifically, an inflammatory autologous disease such as rheumatoid arthritis, psoriasis, multiple sclerosis, colitis, inflammatory bowel disease, systemic lupus erythematosus, and the like. It may be an immune disease, but is not limited thereto.
  • the composition of the invention may inhibit Th2-related cytokine production. Accordingly, the compositions of the present invention can be used for the prevention, amelioration or treatment of various Th2-mediated immune diseases, diseases or conditions. According to another embodiment of the present invention, the composition of the present invention can inhibit cytokine production selected from the group consisting of IL-4 and IL-13.
  • Th2 cells refers to a subset of helper T cell lymphocytes that are specified in terms of gene expression, protein secretion, and functional activity. For example, Th2 cells exhibit IL-4, IL-5 and IL-13 cytokine (Th2-related cytokine) expression patterns, and Th2 cells are involved in humoral immune responses.
  • Th2-mediated immune disease refers to a disease involving IgE and mast cells by the production and activity of allergen-specific Th2 cells, preferably an allergic disease. More specifically, the allergic diseases include food allergy, bronchial asthma, allergic rhinitis (acute or chronic), atopic dermatitis, allergic conjunctivitis, allergic otitis media, urticaria and anaphylactic shock, contact hypersensitivity, allergic contact dermatitis, bacteria Allergies, fungal allergies, viral allergies, drug allergies, thyroid and allergic encephalitis.
  • Th1-associated cytokine was determined by oral administration of the Lactobacillus pentosus KF340 strain of the present invention to mice inducing atopic dermatitis and measuring cytokine changes from lymphocytes isolated from lymph nodes at the site of inflammation. It was confirmed that the production of IL-4 and IL-13, which mediate IgE secretion, was induced by inducing degranulation of mast cells with IFN- ⁇ , Th17-associated cytokines IL-17, and Th2-associated cytokines (Example 5- 3).
  • the composition of the present invention may enhance intestinal immune response.
  • the administration of day 0 or Lactobacillus pentosus KF340 strain in atopic dermatitis-induced mice and feces collected at week 8 resulted in increased IgA secretion, IL-inducing IgA secretion It was confirmed that the production of -6 also increased (see Example 7).
  • the term “allergy” refers to a variety of diseases, diseases or abnormalities caused by hypersensitivity to certain substances in the human body, ie, excessive reaction of the body's immune system to substances from outside.
  • the allergic diseases applied to the composition of the present invention are preferably type I immediate hypersensitivity reactions and type IV delayed hypersensitivity reactions.
  • Type I immediate hypersensitivity reactions are bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, allergic otitis media, urticaria and anaphylatic shock, and type IV delayed hypersensitivity is contact hypersensitivity. It is allergic contact dermatitis, bacterial allergy, fungal allergy, viral allergy, drug allergy, thyroiditis and allergic encephalitis.
  • Type I immediate hypersensitivity is divided into two stages, the first stage of which is a Th1 cell reaction that produces IL-12 and IFN- ⁇ , which inhibits the release of IgE and IgG1 and increases the secretion of IgG2a by invasion of allergens.
  • Th2 cell responses that produce IL-4, IL-5 and IL-13 are inclined toward Th2, excessive immune response of Th2 secretes IL-4 and IL-13, and B cells IgE-specific antibodies produced are attached to the surface of mast cells and basophil to prepare for the development of allergy. It is said to be sensitized to allergens.
  • the second stage of the onset of allergy is divided into early and late reactions, and the initial reaction is an allergen reinvading the body to stimulate mast cells and induce a degranulation reaction, which is released by histamine, lipid metabolites, cytokines, etc. Expansion, etc. occur, and the late response is invasion and activation of neutrophils, eosinophils, macrophages, Th2 cells, basophils, etc. in the tissue, causing inflammation to cause atopic dermatitis, rhinitis, asthma.
  • the allergy of the present invention may be allergic contact dermatitis, allergic atopic dermatitis, or food allergy.
  • the atopic dermatitis, food allergy, contact dermatitis inhibitory activity of the Lactobacillus pentosus KF340 strain was confirmed, and not only live bacteria but also heat treated bacteria showed similar effects (Examples 5 and 8). , And 9).
  • novel Lactobacillus pentosus KF340 strain of the present invention may be prepared as a pharmaceutical, health functional food, food, cosmetics, or feed composition.
  • the pharmaceutical composition of the present invention comprises (a) a pharmaceutically effective amount of the Lactobacillus pentosus of the present invention as described above; And (b) a pharmaceutically acceptable carrier.
  • pharmaceutically effective amount means an amount sufficient to achieve the efficacy or activity of the Lactobacillus pentosus described above.
  • the pharmaceutical composition according to the present invention comprises Lactobacillus pentosus KF340 strain as an active ingredient, it may further comprise a pharmaceutically acceptable carrier.
  • pharmaceutically acceptable carriers are conventionally used in the preparation, and include, but are not limited to, saline solution, sterile water, Ringer's solution, buffered saline, cyclodextrin, dextrose solution, maltodextrin solution, glycerol, ethanol, liposomes, and the like. If necessary, other conventional additives such as antioxidants and buffers may be further included.
  • diluents, dispersants, surfactants, binders, lubricants and the like may be additionally added to formulate injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.
  • Suitable pharmaceutically acceptable carriers and formulations can be preferably formulated according to the individual components using methods disclosed in Remington's literature.
  • the pharmaceutical composition of the present invention is not particularly limited in formulation, but may be formulated as an injection, inhalant, or external skin preparation.
  • the pharmaceutical composition of the present invention may be administered orally or parenterally (eg, applied intravenously, subcutaneously, intraperitoneally, or topically) according to a desired method, but preferably may be administered orally.
  • parenterally eg, applied intravenously, subcutaneously, intraperitoneally, or topically
  • the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.
  • pharmaceutically effective amount means an amount sufficient to treat or diagnose a disease at a reasonable benefit / risk ratio applicable to medical treatment or diagnosis, and an effective dose level refers to a patient's disease type, severity, or drug. Can be determined according to the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of treatment, factors including the drug used concurrently and other factors well known in the medical field.
  • the pharmaceutical compositions according to the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, which can be easily determined by those skilled in the art.
  • the effective amount of the pharmaceutical composition of the present invention may vary depending on the age, sex, condition, weight of the patient, the absorption of the active ingredient in the body, the inactivation rate and excretion rate, the type of disease, the drug used in general 0.001 to 150 mg, preferably 0.01 to 100 mg per kg of body weight may be administered daily or every other day, or divided into 1 to 3 times a day.
  • the dosage may be increased or decreased depending on the route of administration, the severity of obesity, sex, weight, age, etc., and the above dosage does not limit the scope of the present invention in any way.
  • the composition of the present invention When the composition of the present invention is prepared as a health functional food composition, the composition comprises a tablet, pill, powder, granule, powder, capsule, and liquid formulation, including one or more of a carrier, diluent, excipient, and additive. Characterized in that formulated as one selected from. Foods which can be added to the composition of the present invention include various foods, powders, granules, tablets, capsules, syrups, beverages, gums, teas, vitamin complexes, and health functional foods.
  • additives which may be further included in the present invention, natural carbohydrates, flavoring agents, nutrients, vitamins, minerals (electrolytes), flavoring agents (synthetic flavoring agents, natural flavoring agents, etc.), colorants, fillers, pactic acid and salts thereof, Alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonation agents and one or more components selected from the group consisting of pulp can be used.
  • natural carbohydrates examples include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
  • compositions according to the invention include various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic and natural flavors, colorants and neutralizers, fact acids and their salts, alginic acids and their salts, organic acids, protective colloidal thickeners , pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, etc.
  • the composition of the present invention may contain pulp for the production of natural fruit juices and vegetable drinks. These components may be used independently or in combination.
  • carrier examples include, but are not limited to, lactose, dextrose, Chromose, sorbitol, mannitol, erythritol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium phosphate, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, polyvinylpyrrolidone, methylcellulose, water, Preference is given to using at least one selected from the group consisting of sugar syrup, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate and mineral oil.
  • the anti-allergic composition containing the active ingredient of the Lactobacillus pentosus KF340 strain of the present invention is prepared as a cosmetic composition, it contains components commonly used in cosmetic compositions in addition to Lactobacillus pentosus as an active ingredient, for example, a stabilizer. , Conventional adjuvants such as solubilizers, vitamins, pigments and flavorings, and carriers.
  • the cosmetic composition of the present invention may be prepared in any formulation commonly prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing , Oils, powder foundations, emulsion foundations, wax foundations and sprays, and the like, but are not limited thereto. More specifically, it may be prepared in the form of a flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.
  • the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
  • animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
  • animal oils vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide
  • cellulose derivatives polyethylene glycols
  • silicones bentonites
  • silicas talc or zinc oxide
  • the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
  • animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
  • animal oils vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide
  • cellulose derivatives polyethylene glycols
  • silicones bentonites
  • silicas talc or zinc oxide
  • lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.
  • a solvent, solubilizer or emulsifier is used as the carrier component, such as water, ethanol, isopropanol, ethylcarbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.
  • liquid carrier diluents such as water, ethanol or propylene glycol
  • suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.
  • the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide.
  • Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
  • the anti-allergic composition containing the active ingredient Lactobacillus pentosus KF340 strain of the present invention when prepared as a feed composition, it can be prepared by adding Lactobacillus pentosus as it is, or additives commonly added during feed preparation. have. For example, various nutrients such as vitamins, amino acids and minerals, antioxidants, antibiotics, antibacterial agents and other additives.
  • the shape includes powder, granules, pellets or suspensions and the like.
  • composition of the present invention When the composition of the present invention is made of a feed composition, it may be supplied alone or mixed with the feed to land or aquatic animals.
  • the feed of the present invention includes, but not limited to, powder feed, solid feed, moist pellet feed, dry pellet feed, EP (Extruder Pellet) feed, feeding.
  • Strains having the prophylactic, ameliorating or therapeutic activity of the Th1-mediated immune disease, Th17-mediated immune disease or Th2-mediated immune disease of the present invention include the above-mentioned Th1-mediated immune disease, Th17-mediated immune disease or Th2-mediated immune disease. Since the composition for preventing, ameliorating, or treating a compound and the target disease are common, common contents in relation to the composition are omitted in order to avoid excessive complexity of the present specification.
  • strains were isolated from traditionally prepared kimchi using Lactobacillus MRS agar medium (MRS medium, BD288130, Diffcosa, USA), and the isolated strains were identified by 16S rDNA sequencing.
  • MRS medium Lactobacillus MRS agar medium
  • BD288130 Lactobacillus MRS agar medium
  • Diffcosa Lactobacillus MRS agar medium
  • the 16s rDNA sequence (SEQ ID NO: 1) of the strain showed 99.73% homology with the existing Lactobacillus pentosus JCM1558 (T) strain.
  • the medium composition for the cultivation of the strain is MRS medium
  • the culture conditions are pH 6.5 ⁇ 0.2, temperature 37 °C and stationary culture for 48 hours
  • oxygen urinary tract is anaerobic
  • strain preservation through freeze-drying preservation or cell suspension freezing It is possible.
  • the present inventors named the strain Lactobacillus pentosus KF340, and deposited it on March 6, 2015 to the Korea Microorganism Conservation Center (KCCM), an international microbial deposit institution, and was given accession number KCCM 11675P.
  • KCCM Microorganism Conservation Center
  • mice system number-C57BL / 6, stock number-000664, the Jackson laboratory
  • genetically modified mice Foxp3-GFP knockout mice, line name-B6.Cg-Foxp3 tm2Tch / J, Stock No.-006772, Jackson laboratory
  • EGFP enhanced green fluorescence protein
  • lymph nodes After mesenteric lymph nodes (MLNs) of mice were extracted, immune cells (mostly lymphocytes) present in lymph nodes were suspended in single cells and used for experiments. Since probiotics present in the gut are recognized by immune cells present in the intestinal immune system, suitable immune cells for characterizing probiotics are immune cells present in the mesenteric lymph nodes. Therefore, the characteristics of Lactobacillus pentosus KF340 were analyzed by the immune cells isolated from the lymph nodes.
  • the immune cells and Lactobacillus pentosus KF340 isolated according to the above method was incubated in a 1:10 ratio, that is, immune cells 3 ⁇ 10 6 and strain 3 ⁇ 10 7 cfu at 37 ° C. in a CO 2 incubator for 72 hours.
  • the antibiotic gentamicin 11811-031, 15 ⁇ g / mL, GIBCO was treated together to prevent overgrowth of the test strain.
  • ELISA is one of the methods of measuring the amount of antigen or antibody using an antigen-antibody reaction using an enzyme as a marker.
  • the detection antibody to be treated is bound to the enzyme (HRP), the color change occurs as a result of the enzyme-substrate reaction by adding the enzyme substrate (Tetramethylbenzidine Substrate Solution, eBioscience).
  • HRP enzyme-substrate reaction
  • the enzyme substrate Tetramethylbenzidine Substrate Solution, eBioscience.
  • IL-10 (interleukin 10) is a representative immune tolerant cytokine
  • IL-12 (interleukin 12) is known as a representative immunologically active cytokine. Therefore, the lactic acid bacteria having antiallergic properties are selected by identifying the absolute / relative amounts of the two cytokines. can do.
  • mesenteric lymph node cells of Foxp3 knock-in mice were isolated and mixed with each test strain in a ratio of 1:10 according to the method of Example 2-2, followed by co-culture.
  • Foxp3 is a transcription factor of regulatory T cells, which is a subset of T cells that suppress excessive immunity, and the distribution of regulatory T cells can be confirmed through the degree of Foxp3 expression.
  • the regulatory T cell is one of a subset of T cells and serves to suppress an excessive immune response unlike other T cells.
  • Various studies have supported that these T cells suppress allergic diseases. Therefore, when co-culturing test strains and mesenteric lymph node cells, strains that can increase the distribution of regulatory T cells will become probiotics with antiallergic efficacy. Most likely.
  • mesenchymal lymph node immune cells isolated according to the method of Example 3-1 were subjected to flow cytometry.
  • the expression level of Foxp3 was measured and compared by measuring the GFP signal that co-expresses at the time of expression.
  • a mixture of OVA (20 ⁇ g) and aluminium (aluminum hydroxide gel, 2 mg) was mixed for 30 minutes, and then injected into the 5-week old female Balb / c mice intraperitoneally twice at a weekly interval of 100 ⁇ l per horse. Induced.
  • the mouse spleens were extracted and single-celled and hemolyzed splenocytes were dispensed at 5 ⁇ 10 6 cells / well in 96-well plates.
  • the antigen OVA, 100 ⁇ g / mL
  • the Lactobacillus pentosus KF340 5 ⁇ 10 7 CFU / well
  • the secretion amount of IL-4 was measured.
  • Control group 1 allergy-induced experimental group
  • control group 2 allergy-induced experimental group
  • mice were subjected to oral administration of Lactobacillus pentosus KF340 strain at least 5 ⁇ 10 8 CFU / day five times a week for eight weeks.
  • the ears of the mouse were removed using a surgical tape, followed by 1.0% DNCB (2,4-dinitrochlorobenzene) and 20 ⁇ l of house dust mite (10). mg / mL) was applied.
  • atopic dermatitis was induced by repeating 5 weeks in a manner of alternately treating 1% DNCB and 20 ⁇ l (10 mg / mL) of ticks once a week.
  • Example 5-1 the Lactobacillus pentosus KF340 strain was administered to the house dust mite-induced atopic dermatitis mouse model for 8 weeks, and then histologic changes were measured to evaluate anti-atopic activity.
  • the experiment was conducted under the same conditions using dexamethasone (dexamethasone), which is a steroid used to treat atopic dermatitis.
  • lymphocytes were isolated from the lymph nodes of the inflamed area of the mouse (surface lymph nodes, axillary lymph nodes, bronchial lymph nodes), and then stimulated with an antigen house dust mite. It was confirmed by ELISA method using a cytokine quantitative kit from Bioscience.
  • lymphocytes were isolated from Payer's patches (hereinafter referred to as PPs) and mesenteric lymph nodes (mLN) corresponding to gut-associated lymphoid tissue (GALT), and the Th2 cytokine IL-4 was isolated in the same manner.
  • PPs Payer's patches
  • MNL mesenteric lymph nodes
  • GALT gut-associated lymphoid tissue
  • Example 5-2 and 5-3 confirmed that the Lactobacillus pentosus KF340 live bacteria exhibited anti-atopic activity, it was intended to verify whether the bacterium also exhibits the same anti-atopic activity.
  • the atopic dermatitis mouse model was prepared in the same manner as in Example 5-1, and the live Lactobacillus pentosus KF340 microorganisms or the dead bacteria prepared by heat-treating them at 121 ° C. for 15 minutes were administered to the mice in the same manner.
  • Th17 cells and IL-17A changes in Th17 cells and IL-17A following Lactobacillus pentosus KF340 live or dead administration were measured.
  • Most T cell mediated diseases are thought to be caused by Th1 / Th2, but recently, Th17 cells secreting IL-17 have been reported to play an important role in skin immunity.
  • IL-17A is a major cytokine produced by Th17 cells and is known to play an important role in tissue inflammatory response and to bring neutrophils into tissues.
  • Example 3-1 confirmed that the Lactobacillus pentosus KF340 strain increased the production of IL-10, the strain affects cells that induce IL-10 secretion in addition to regulatory T cells, thereby inhibiting antiallergic activity. As determined, the cells secreting IL-10 were screened in vitro and in vivo using a flow cytometer (COULTER Epics XL, BECKMAN).
  • B10 cells (phenotype: B220 + CD5 + CD1d + or CD19 + CD5 + CD1d +) are a subset of regulatory B cells that have been reported to inhibit allergy by secreting a large number of IL-10 cytokines specifically in the spleen, It is known to play an important role in regulating inflammatory and autoimmune responses.
  • Lactobacillus pentosus KF340 strain increased the population of B220 + CD5 + CD1d + B cells in the spleen, but since it was very unlikely that it directly acted on the spleen, It is possible that it acted on the spleen as a secondary response.
  • the group 340 administered the strain compared to the control group was found to have a higher frequency of dendritic cells (hereinafter referred to as DC) in the PPs.
  • the increased DC showed a pattern showing a decrease in the expression of CD80, CD86.
  • Example 6-2 Based on the results of Example 6-2, it was determined that the inhibitory DC may move from the lymphoid tissue to the spleen to affect the splenocytes, thereby inducing the induction of regulatory B cells by direct or indirect effects.
  • the direct effect on the DC of the Lactobacillus pentosus KF340 strain was attempted.
  • BMDC bone marrow dendritic cells
  • the Lactobacillus pentosus KF340 strain exhibiting anti-atopic effect in the atopic dermatitis model increases IL-10 secretion by increasing the population of B220 + CD5 + CD1d + B10 cells in the spleen, a type of regulatory B cell. It was confirmed to have.
  • This increase in B10 cells promotes the production of IL-10 and BAFF by inducing DCs of PPs to which the Lactobacillus pentosus KF340 strain is absorbed into inhibitory DCs, or migrates to the spleen through lymph nodes to directly induce B10 cells. It is considered to be.
  • atopic dermatitis was induced in mice in the same manner as in Example 5-1, and the Lactobacillus pentosus KF340 strain was orally administered and secreted according to the strain administration.
  • the concentration of type IgA was measured.
  • fecals were collected from mice on week 0 and 8 weeks after the end of the experiment, and then the amount of cytokine IL-6, which induces the secretion of IgA and IgA in feces, was measured using BD's mouse IgA quantitative kit.
  • the production of IgA was increased by administration of Lactobacillus pentosus KF340 strain in mice induced by atopic dermatitis.
  • IL-6 it was confirmed that IL-6 production, which induces IgA secretion, is increased in the payer's patch.
  • the results show that the Lactobacillus pentosus KF340 strain induces the production of IgA and affects mucosal immunity enhancement.
  • mice received 5 weeks old female BALB / c mice from Orient Bio Co., Ltd., and were used after breeding and purifying for one week in the experimental animal room.
  • 100 ⁇ l per horse was injected intraperitoneally with OVA (20 ⁇ g) and alum (2 mg) mixed solution, followed by primary immunization.
  • OVA OVA
  • alum (2 mg) mixed solution followed by primary immunization.
  • the Lactobacillus pentosus KF340 strain was administered daily at a concentration of 5 ⁇ 10 8 CFU / day.
  • the normal control group (Naive) was administered the same amount of suspension solvent PBS instead of the Lactobacillus pentosus KF340 suspension, the positive control group (PC (daxa)) was administered dexamethasone, an immunosuppressive agent.
  • Allergenicity was induced by oral administration of OVA at a concentration of 50 mg / mice / day to all groups at 3 day intervals after 14 days of secondary immunity to induce food allergy.
  • Anaphylaxis and diarrhea reactions which are food allergens, were measured at 30-minute intervals after oral administration of OVA. Changes in rectal temperature were measured at 60-minute intervals for 20 minutes.
  • Lactobacillus pentosus KF340 strain decreased IgE, which is closely related to allergic symptoms.
  • the Lactobacillus pentosus KF340 was administered at a concentration of 5 ⁇ 10 8 CFU / horse daily after the first sensitization, and the Siamese group was administered the same amount of PBS used to suspend the Lactobacillus pentosus KF340. The experiment was performed by treating P).
  • TMA is a type of chemical hapten that induces allergic hypersensitivity of immune cells by invading the skin through the skin and invading the skin, and induces a strong Th2 response. Inflammation of the site and increased thickness of the tissue. As a result, as shown in FIG. 12, the TMA-treated ear thickness decreased with Lactobacillus pentosus KF340 compared to the negative control.
  • DLN and spleen were removed from each group of mice, and then cultured for 96 hours after 3x10 6 cells after unicellular suspension.
  • the cells were divided into two cases in which only 10 ⁇ g of mites were treated and only cells were cultured to confirm the antigen-specific reaction.
  • the cytokines in the supernatant after 96 hours of cultivation were analyzed using the cytokine quantification kit of e-Bioscience. It was confirmed by the ELISA method.

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Abstract

La présente invention concerne : une souche KF340 de Lactobacillus pentosus(numéro d'enregistrement KCCM 11675P); et une composition permettant de prévenir, de soulager ou de traiter des maladies immunitaires médiées par Th1, Th17 ou Th2, la composition contenant ladite souche en tant que principe actif. La nouvelle souche KF340 de Lactobacillus pentosus selon l'invention permet de contrôler de manière efficace les allergies et inflammations en induisant des lymphocytes T régulateurs et des lymphocytes B régulateurs, en régulant le rapport d'une cytokine tolérante à l'immunité (IL-10; cytokine anti-inflammatoire) sur une cytokine activant l'immunité (IL-12), en inhibant la génération de l'immunoglobuline E (IgE), en inhibant la génération de cytokines associées à Th1, de cytokines associées à Th17 et de cytokines associées à Th2 lors de réactions d'hypersensibilité immunitaire, et en favorisant des réactions immunitaires intestinales en fonction de la sécrétion d'IgA. La souche est ainsi susceptible d'être utilisée sous forme de composition pour prévenir, soulager ou traiter des maladies immunitaires médiées par Th1, Th17 ou Th2 et, plus préférablement, des allergies ou des maladies inflammatoires.
PCT/KR2016/003202 2015-08-13 2016-03-29 Composition pour prévenir, soulager ou traiter des maladies immunes médiées par th1, th17 ou th2, la composition contenant, comme principe actif, lactobacillus pentosus WO2017026620A1 (fr)

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KR10-2015-0114938 2015-08-13
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KR1020160026193A KR101761506B1 (ko) 2015-08-13 2016-03-04 락토바실러스 펜토서스를 유효성분으로 포함하는 Th1-매개 면역 질환, Th17-매개 면역 질환, 또는 Th2-매개 면역 질환의 예방, 개선, 또는 치료용 조성물

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20070033376A (ko) * 2004-05-28 2007-03-26 산토리 가부시키가이샤 락토바실러스 펜토서스를 포함하는 면역조절작용을 갖는조성물
KR20100045758A (ko) * 2008-10-24 2010-05-04 경북대학교 산학협력단 장내효소활성, 내산성, 내담즙성이 우수한 신규 락토바실러스 펜토서스 pl-11 균주와 이를 이용한 어류용프로바이오틱스
JP2011004620A (ja) * 2009-06-23 2011-01-13 Tokai Igaku Kensa Kenkyusho:Kk ラクトバチルス属菌株及び前記菌株を含有する食品及び医薬品
KR20120107106A (ko) * 2009-12-22 2012-09-28 프로비 아베 곡물 기저의 분획 및 프로바이오틱을 포함하는 비-발효 조성물 및 그 용도
WO2014170595A1 (fr) * 2013-04-15 2014-10-23 Greentech Applications cosmétiques et pharmaceutiques de lactobacillus pentosus

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20070033376A (ko) * 2004-05-28 2007-03-26 산토리 가부시키가이샤 락토바실러스 펜토서스를 포함하는 면역조절작용을 갖는조성물
KR20100045758A (ko) * 2008-10-24 2010-05-04 경북대학교 산학협력단 장내효소활성, 내산성, 내담즙성이 우수한 신규 락토바실러스 펜토서스 pl-11 균주와 이를 이용한 어류용프로바이오틱스
JP2011004620A (ja) * 2009-06-23 2011-01-13 Tokai Igaku Kensa Kenkyusho:Kk ラクトバチルス属菌株及び前記菌株を含有する食品及び医薬品
KR20120107106A (ko) * 2009-12-22 2012-09-28 프로비 아베 곡물 기저의 분획 및 프로바이오틱을 포함하는 비-발효 조성물 및 그 용도
WO2014170595A1 (fr) * 2013-04-15 2014-10-23 Greentech Applications cosmétiques et pharmaceutiques de lactobacillus pentosus

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