WO2017047962A1 - Nouveau lactobacillus et composition pour prévenir, atténuer ou traiter des maladies cérébrales dégénératives ou des troubles de la fonction cognitive - Google Patents

Nouveau lactobacillus et composition pour prévenir, atténuer ou traiter des maladies cérébrales dégénératives ou des troubles de la fonction cognitive Download PDF

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WO2017047962A1
WO2017047962A1 PCT/KR2016/009961 KR2016009961W WO2017047962A1 WO 2017047962 A1 WO2017047962 A1 WO 2017047962A1 KR 2016009961 W KR2016009961 W KR 2016009961W WO 2017047962 A1 WO2017047962 A1 WO 2017047962A1
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dementia
disease
lactic acid
acid bacteria
lactobacillus
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PCT/KR2016/009961
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English (en)
Korean (ko)
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김동현
한명주
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경희대학교 산학협력단
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Priority claimed from KR1020160001312A external-priority patent/KR20170032815A/ko
Application filed by 경희대학교 산학협력단 filed Critical 경희대학교 산학협력단
Priority to CN201680066260.6A priority Critical patent/CN108603162B/zh
Priority to EP16846783.5A priority patent/EP3351616A4/fr
Priority to US15/759,928 priority patent/US10471111B2/en
Priority to JP2018513764A priority patent/JP6626569B2/ja
Priority to CA2998877A priority patent/CA2998877C/fr
Priority to NZ741028A priority patent/NZ741028A/en
Priority to SG11201802145SA priority patent/SG11201802145SA/en
Priority to AU2016324846A priority patent/AU2016324846B2/en
Publication of WO2017047962A1 publication Critical patent/WO2017047962A1/fr
Priority to HK18113645.2A priority patent/HK1254665A1/zh

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • 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
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • 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
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • 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
    • C12R2001/225—Lactobacillus
    • 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
    • C12R2001/225—Lactobacillus
    • C12R2001/24—Lactobacillus brevis

Definitions

  • the present invention relates to a novel lactic acid bacteria and uses thereof, and more particularly, it is isolated from kimchi, memory improving activity, tight junction protein expression inducing activity, antioxidant activity, lipopolysaccharide (LPS) production inhibitory activity Or a novel lactic acid bacterium having various physiological activities such as beta-glucuronidase inhibitory activity and the like, as well as food, pharmaceutical use, such as prevention, improvement or treatment of degenerative brain disease or cognitive dysfunction.
  • LPS lipopolysaccharide
  • Alzheimer's disease is the most common degenerative brain disease that causes dementia and gradually progresses to deterioration of cognitive function, including memory. Alzheimer's disease has not yet been pinpointed, but it is closely related to aging and is increasing as the elderly population increases.
  • Parkinson's disease is a chronic progressive degenerative disease of the nervous system caused by the loss of dopamine neurons, and symptoms such as muscle spasms, slowness in motion and postural instability. Alzheimer's patients show dementia symptoms such as speech impairment and impairment, while Parkinson's patients exhibit dementia symptoms such as poor concentration, poor visual and spatial judgment, impaired execution and slow thinking.
  • Dementia is a state in which people with normal deterioration have damaged brain function due to a variety of causes, and the cognitive function is deteriorated and overall deteriorated as compared to the past, which is a significant obstacle in daily life.
  • cognitive function refers to various intellectual abilities such as memory, language ability, space-time grasping ability, judgment ability and abstract thinking ability. Each cognitive function is closely related to a specific brain region. About 50% of dementia is Alzheimer's disease, 20-30% is vascular dementia, and alcoholic dementia, Lewy body dementia, frontal lobe degeneration, and Parkinson's dementia. Recently, various degenerative brain diseases such as dementia have been reported to be associated with intestinal leak syndrome or disruption of the intestinal bacterial flora.
  • the digestive tract of our body is composed of mucus and villi, which efficiently absorb nutrients and prevent the absorption of high molecular weight pathogens and their toxins.
  • our body has an immune system that can protect against high molecular weight foreign antigens invading the body.
  • the intestinal bacterial flora is disturbed by infections of many hospital microorganisms or toxins, excessive stress, food intake such as high-fat diets that can multiply harmful bacteria in the digestive tract, excessive alcohol intake, and abuse of drugs (eg antibiotics).
  • drugs eg antibiotics
  • Intestinal Permeability Syndrome (Leaky Gut Syndrome) is a leaky gut syndrome, and the tightly connected defense system of the epithelial cells that make up the gastrointestinal tract is not working well. It is a condition that continues to flow into the blood.
  • intestinal leak syndrome When intestinal leak syndrome occurs, external antigens that are not absorbed into the body generally enter the body, so ulcerative colitis, Crohn's disease, liver damage, liver dysfunction, allergic diseases (including asthma), atopy, autoimmune diseases, lipodiasis, Digestive absorption disorders, acne, aging, endotoxins, intestinal infections, eczema, hypersensitivity syndrome, chronic fatigue syndrome, psoriasis, rheumatoid arthritis, pancreatic insufficiency, inflammatory joint disease, etc. Recently, it has been reported that intestinal leak syndrome is associated with Parkinson's disease and dementia caused by aging.
  • Microorganisms harmful to the intestinal flora eg, Klebsiella pneumoniae , Escherichia coli , Proteus Increasing mirabilis, etc., may activate NF- ⁇ B in the intestinal cells, making it more likely to be associated with degenerative brain diseases such as Alzheimer's and Parkinson's.
  • probiotics In the gastrointestinal tract of animals including humans, living organisms that improve the host's intestinal microbial environment and have beneficial effects on the health of the host are collectively called probiotics. In order to be effective as a probiotic, when ingested orally, most of them must reach the small intestine and adhere to the intestinal surface. Therefore, the resistance to acid, bile and intestinal epithelial cells should be excellent. Lactic acid bacteria are used as probiotics because they play a role in breaking down fiber and complex proteins into important nutrients while living in the digestive system of the human body.
  • Lactobacillus has been reported to show the effects of maintaining normal intestinal flora, improving intestinal flora, antidiabetic and antihyperlipidemic effects, inhibiting carcinogenesis, inhibiting colitis, and nonspecific activity of the host's immune system.
  • the strain Lactobacillus is a major member of the normal microbial community in the intestine of the human body, which has long been known to be important for maintaining a healthy digestive system and the vaginal environment, and the US Public Health Service (US Public Health Service). guidelines) are currently classified as 'Bio-safty Level 1', where none of the Lactobacillus strains currently deposited with the American Strain Deposit Organization (ATCC) is known about the potential risk of causing disease in humans or animals.
  • ATCC American Strain Deposit Organization
  • kimchi lactic acid bacteria are reported to have the effect of immuno-enhancing, anti-microbial, antioxidant, anti-cancer, anti-obesity, hypertension or constipation as a lactic acid bacteria involved in kimchi fermentation [Hivak P, Odrska J, Ferencik M, Ebringer L, Jahnova E, Mikes Z .: One-year application of Probiotic strain Enterococcus facium M-74 decreases Serum cholesterol levels. Bratisl lek Listy 2005; 106 (2); 67-72; Agerholm-Larsen L. Bell ML. Grunwald GK.
  • Astrup A The effect of a probiotic milk product on plasma cholesterol: a metaanalysis of short-term intervention studies; Eur J Clin Nutr. 2000; 54 (11) 856-860; Renato Sousa, Jaroslava Helper, Jian Zhang, Strephen J Lewis and Wani O Li; Effect of Lactobacillus acidophilus supernants on body weight and leptin expression in rats; BMC complementary and alternative medicine. 2008; 8 (5) 1-8].
  • Republic of Korea Patent Publication No. 10-1476236 discloses a pharmaceutical composition for the prevention or treatment of dementia comprising the Lactobacillus pentosus strain plantarium C29 KCCM11291P strain as an active ingredient.
  • Republic of Korea Patent Publication No. 10-1476236 discloses a pharmaceutical composition for the prevention or treatment of dementia comprising the Lactobacillus pentosus strain plantarium C29 KCCM11291P strain as an active ingredient.
  • 10-1424547 discloses a pharmaceutical composition for the prevention or treatment of degenerative brain diseases, including Lactobacillus fermentum KFRI 164 ( Lactobacillus fermentum KFRI 164) lactobacillus fermentation product as an active ingredient have.
  • Korean Patent Publication No. 10-2015-0047687 discloses 0.1 to 10% by weight glucose and 0.1 to 5% by weight yeast extract with respect to 100% by weight of plant extracts extracted from hot water, Baekbokyeong and Seokchangpo. It is disclosed that the composition for enhancing memory or preventing forgetfulness or improving amnesia containing a fermented plant extract fermented by inoculating the cultured Lactobacillus plantarum (fermented Lactobacillus plantarum ) as an active ingredient.
  • the products fermented by the lactic acid bacteria or lactic acid bacteria disclosed in the prior art is not high in the therapeutic effect of degenerative brain diseases such as dementia, there is a limit to commercial applications. Therefore, there is also a need for the development of drugs, functional foods, and the like, screening of lactic acid bacteria, which are similar to commercial therapeutic agents and can improve intestinal bacterial flora, disturbance of intestinal bacteria, and intestinal leak syndrome.
  • the present invention has been derived under such a conventional technical background, and an object of the present invention is to provide a novel lactic acid bacteria having various physiological activities or functionalities required as probiotics.
  • Lactobacillus zone Sony (Lactobacillus johnsonii) comprising a base sequence shown in SEQ ID NO: 2 with 16S rDNA, memory improved activity, adhesion synaptic protein (tight junction protein) expression induction It provides a lactic acid bacterium having activity, antioxidant activity, lipopolysaccharide (LPS) production inhibitory activity or beta-glucuronidase ( ⁇ -glucuronidase) inhibitory activity.
  • LPS lipopolysaccharide
  • ⁇ -glucuronidase beta-glucuronidase
  • an example of the present invention is a lactic acid bacteria, Lactobacillus johnsonii ( Lactobacillus johnsonii ) Lactobacillus , including the nucleotide sequence of SEQ ID NO: 2 as 16S rDNA, the culture of the lactic acid bacteria, the lysate of the lactic acid bacteria or It provides a pharmaceutical composition comprising the extract of the lactic acid bacteria as an active ingredient, and for use in preventing or treating degenerative brain disease or cognitive impairment.
  • one embodiment of the present invention is a 16S rDNA containing the nucleotide sequence of SEQ ID NO: 2 and corresponding to Lactobacillus johnsonii ( Lactobacillus johnsonii ) Lactobacillus, the culture of the lactic acid bacteria, the lysate of the lactic acid bacteria or extract of the lactic acid bacteria Provided as an active ingredient, a food composition for use for preventing or improving degenerative brain disease or cognitive impairment.
  • one embodiment of the present invention is a 16S rDNA containing the nucleotide sequence of SEQ ID NO: 2 and corresponding to Lactobacillus johnsonii ( Lactobacillus johnsonii ) Lactobacillus, the culture of the lactic acid bacteria, the lysate of the lactic acid bacteria or extract of the lactic acid bacteria It is included as an active ingredient and provides a food composition for use for improving memory or learning ability.
  • another example of the present invention comprises a red bean fermented product or the extract of the red bean fermented product as an active ingredient, and provides a pharmaceutical composition for use in preventing or treating degenerative brain disease or cognitive impairment.
  • another embodiment of the present invention comprises a red bean fermented product or the extract of the red bean fermented product as an active ingredient, and provides a food composition for use for preventing or improving degenerative brain disease or cognitive impairment.
  • another embodiment of the present invention comprises a red bean fermented product or the extract of the red bean fermented product as an active ingredient, and provides a food composition for improving memory or learning ability.
  • the red bean fermented product is a product of red beans fermented with lactic acid bacteria corresponding to Lactobacillus johnsonii ( Lactobacillus johnsonii ) containing the nucleotide sequence of SEQ ID NO: 2 as 16S rDNA.
  • Specific Lactobacillus strain according to the present invention is isolated from kimchi has high safety and memory improvement activity, tight junction protein expression inducing activity, antioxidant activity, lipopolysaccharide (LPS) production inhibitory activity or beta-glu It has a variety of physiological activities, such as kurondase ( ⁇ -glucuronidase) inhibitory activity. Therefore, the specific Lactobacillus strain according to the present invention is a drug or health function for preventing, improving or treating various diseases through a combination of the primary effect of improving intestinal leakage and the secondary effect of improving learning or memory It can be used as food material.
  • LPS lipopolysaccharide
  • FIG. 1 is a graph showing the effect of Lactobacillus johnsonii CH32 administration on the Y-maze test of a model animal induced memory impairment by Escherichia coli K20 strain.
  • FIG. 2 is a graph showing the effect of Lactobacillus johnsonii CH32 administration on the passive avoidance test of a model animal induced memory impairment by Escherichia coli K20 strain.
  • FIG. 3 is a photograph showing the effect of Lactobacillus johnsonii CH32 administration on the expression level of nerve growth promoter in model animals induced memory impairment by Escherichia coli K20 strain.
  • cogntive impairment refers to a symptom or disease in which cognitive function such as memory processing, perception or problem solving is not normally performed, and specifically, working memory, attention and vigilance, language learning and Memory, visual learning and memory, reasoning and problem solving such as impairment of executive function, processing speed or social cognition.
  • brain disease refers to any disease that occurs in the brain by the destruction of cranial nerve cells.
  • culture means a product obtained by culturing a microorganism in a known liquid medium or a solid medium, and is a concept in which a microorganism is included.
  • the term “fermented product” refers to a product obtained by fermenting a raw material to be fermented with a predetermined microorganism, and is a concept in which microorganisms are included.
  • lactic acid bacteria refers to lactic acid bacteria, cultures of the lactic acid bacteria, lysates of the lactic acid bacteria or extracts of the lactic acid bacteria.
  • red bean fermented product refers to red bean fermented product or extract of the red bean fermented product.
  • pharmaceutically acceptable and “food acceptable” means that they do not significantly stimulate the organism and do not inhibit the biological activity and properties of the administered active substance.
  • prevention means any action that inhibits the symptoms or delays the progression of a particular disease by administration of a composition of the present invention.
  • treatment means any action that improves or beneficially alters the symptoms of a particular disease by administration of a composition of the present invention.
  • improvement refers to any action that at least reduces the parameters associated with the condition being treated, for example, the extent of symptoms.
  • the term "administration" means providing a subject with a composition of the present invention in any suitable manner.
  • the subject refers to all animals, such as humans, monkeys, dogs, goats, pigs or mice having a disease that can improve the symptoms of a particular disease by administering the composition of the present invention.
  • the term "pharmaceutically effective amount” refers to an amount sufficient to treat a disease at a reasonable benefit or risk ratio applicable to medical treatment, which refers to the type of disease, the severity, the activity of the drug, the drug, and the like. Sensitivity, time of administration, route of administration and rate of excretion, duration of treatment, factors including drug used concurrently, and other factors well known in the medical arts.
  • Lactobacillus according to an embodiment of the present invention is Lactobacillus johnsonii comprising the nucleotide sequence of SEQ ID NO: 2 as 16S rDNA, memory improving activity, tight junction protein expression inducing activity, antioxidant activity , Lipopolysaccharide (LPS) production inhibitory activity or beta-glucuronidase ( ⁇ -glucuronidase) inhibitory activity.
  • the Lactobacillus johnsonii is an anaerobic bacillus isolated from kimchi, shows positive gram staining, can survive in a wide temperature range, low pH environment, and produces glucosidase.
  • Lactobacillus johnsonii ( Lactobacillus johnsonii ) is a carbon source D-glucose, D-fructose, D- mannose, N-acetyl-glucosamine (N-acetyl-glucosamine), maltose, lactose, sucrose (Sucrose) ), Geniobiose and the like.
  • the Lactobacillus johnsonii ( Lactobacillus johnsonii ) is preferably Lactobacillus johnsonii CH32 (Accession Number: KCCM 11763P).
  • compositions comprising a specific lactic acid bacteria and the like as an active ingredient.
  • the composition according to one embodiment of the present invention comprises the nucleotide sequence of SEQ ID NO: 2 as 16S rDNA and corresponds to Lactobacillus johnsonii ( Lactobacillus johnsonii ), lactic acid bacteria, culture of the lactic acid bacteria, lysates of the lactic acid bacteria or extracts of the lactic acid bacteria Include as an active ingredient.
  • Lactobacillus johnsonii is an anaerobic bacillus isolated from kimchi, shows positive gram staining, can survive in a wide temperature range, low pH environment, and produces glucosidase.
  • Lactobacillus johnsonii ( Lactobacillus johnsonii ) is a carbon source D-glucose, D-fructose, D- mannose, N-acetyl-glucosamine (N-acetyl-glucosamine), maltose, lactose, sucrose (Sucrose) ), Geniobiose and the like.
  • the Lactobacillus johnsonii ( Lactobacillus johnsonii ) is preferably Lactobacillus johnsonii CH32 (Accession Number: KCCM 11763P).
  • the culture of lactic acid bacteria in the present invention is a product obtained by culturing a predetermined strain or mixed strain in a medium
  • the medium may be selected from known liquid medium or solid medium, for example MRS liquid medium, MRS agar medium , BL agar medium.
  • Composition according to an embodiment of the present invention is lactic acid bacteria, such as the active ingredient, memory improving activity, tight junction protein expression inducing activity, antioxidant activity, lipopolysaccharide (LPS) production inhibitory activity or beta-glucuro Since it has various physiological activities such as nidase ( ⁇ -glucuronidase) inhibitory activity, it can be used for the prevention, improvement or treatment of degenerative brain disease or cognitive impairment.
  • the degenerative brain disease may be specifically Alzheimer's disease, Parkinson's disease, Huntington's disease or dementia.
  • the dementia may include senile dementia, vascular dementia, Lewy body dementia, anterior temporal dementia, Alzheimer's disease dementia, Parkinson's disease dementia, and Huntington's disease.
  • composition according to an embodiment of the present invention can also be used for the purpose of improving memory or learning ability.
  • compositions comprising a product fermented by lactic acid bacteria and the like as an active ingredient.
  • the composition according to another embodiment of the present invention comprises red bean fermented product or extract of the red bean fermented product as an active ingredient.
  • the red bean fermented product is a product of red beans fermented with lactic acid bacteria corresponding to Lactobacillus johnsonii ( Lactobacillus johnsonii ) containing the nucleotide sequence of SEQ ID NO: 2 as 16S rDNA.
  • the technical features of the Lactobacillus johnsonii Lactobacillus johnsonii
  • the red bean fermented product which is an active ingredient of the composition according to another embodiment of the present invention, contains both the secondary metabolite produced by the red bean fermentation and the lactic acid bacteria used in fermenting the red bean, More useful in terms of material.
  • the composition according to another embodiment of the present invention can be used for the purpose of preventing, ameliorating or treating degenerative brain disease or cognitive impairment.
  • the degenerative brain disease may be specifically Alzheimer's disease, Parkinson's disease, Huntington's disease or dementia.
  • the dementia may include senile dementia, vascular dementia, Lewy body dementia, anterior temporal dementia, Alzheimer's disease dementia, Parkinson's disease dementia, and Huntington's disease.
  • composition according to another embodiment of the present invention can also be used for the purpose of improving memory or learning ability.
  • the composition may be embodied as a pharmaceutical composition, a food additive, a food composition (particularly a functional food composition), a feed additive, and the like according to the purpose or aspect of use.
  • the content of such as lactic acid bacteria or red bean fermented product as an active ingredient may also be adjusted in various ranges according to the specific form of the composition, purpose of use and aspects.
  • the content of an active ingredient is not particularly limited.
  • 0.01 to 99% by weight preferably 0.5 to 50% by weight, based on the total weight of the composition.
  • the pharmaceutical composition according to the present invention may further include an additive such as a pharmaceutically acceptable carrier, excipient or diluent in addition to the active ingredient.
  • Carriers, excipients and diluents that may be included in the pharmaceutical compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • the pharmaceutical composition of the present invention may further contain one or more known active ingredients having a prophylactic or therapeutic effect in addition to lactic acid bacteria or red bean fermented products.
  • the pharmaceutical composition of the present invention may be formulated into a formulation for oral administration or a parenteral administration by a conventional method, and when formulated, such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. Diluents or excipients may be used.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose in active ingredients.
  • Lactose Lactose (Lactose) or gelatin can be prepared by mixing.
  • lubricants such as magnesium styrate talc may also be used.
  • Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents, water and liquid paraffin. have.
  • Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
  • base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • it may be preferably formulated according to each disease or component by an appropriate method in the art or using a method disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA.
  • the pharmaceutical composition of the present invention can be administered orally or parenterally to mammals including humans according to a desired method, and parenteral administration methods include external skin, intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, muscle Intra-injection or intrathoracic injection;
  • the dosage of the pharmaceutical composition of the present invention is not particularly limited as long as it is a pharmaceutically effective amount, and the range thereof depends on the weight, age, sex, health condition, diet, time of administration, method of administration, excretion rate and severity of the disease. Varies.
  • Typical daily dosages of the pharmaceutical compositions of the present invention are not particularly limited but are preferably 0.1 to 3000 mg / kg, more preferably 1 to 2000 mg / kg, once daily based on the active ingredient. Or divided into several doses.
  • the content of the lactic acid bacteria or red bean fermented products, such as the active ingredient in the food composition according to the present invention is 0.01 to 99% by weight, preferably 0.1 to 50% by weight, more preferably 0.5 to 25 based on the total weight of the composition. Weight%, but it is not limited to this.
  • the food composition of the present invention includes the form of pills, powders, granules, acupuncture, tablets, capsules, or liquids, and examples of specific foods include meat, sausage, bread, chocolate, candy, snacks, confectionary, pizza, ramen, Other noodles, gums, dairy products, including ice cream, various soups, beverages, tea, functional water, drinks, alcoholic beverages and vitamin complexes, and includes all of the health food in the usual sense.
  • the food composition of the present invention may contain, as an additional component, a food acceptable carrier, various flavors, or natural carbohydrates.
  • a food acceptable carrier various flavors, or natural carbohydrates.
  • the food composition of the present invention is a variety of nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols And carbonation agents used in carbonated beverages.
  • the food composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination.
  • the above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol.
  • natural flavoring agents such as taumartin, stevia extract, synthetic flavoring agents such as saccharin, aspartame, etc. may be used.
  • GAM liquid medium GAM broth; Nissui Pharmaceutical, Japan. Subsequently, the supernatant was taken and transplanted into BL agar medium (Nissui Pharmaceutical, Japan) and incubated anaerobicly at 37 ° C. for about 48 hours, after which colony-forming Bifidobacterium sp. .) Strains were isolated.
  • Table 1 shows the control numbers and strain names of lactic acid bacteria isolated from Chinese cabbage kimchi, radish kimchi, green onion kimchi and human feces.
  • Control Number Strain name Control Number Strain name One Lactobacillus acidophilus CH1 31 Lactobacillus sakei CH31 2 Lactobacillus acidophilus CH2 32 Lactobacillus johnsonii CH32 3 Lactobacillus acidophilus CH3 33 Lactobacillus sakei CH33 4 Lactobacillus brevis CH4 34 Lactobacillus sakei CH34 5 Lactobacillus curvatus CH5 35 Lactobacillus plantarum CH35 6 Lactobacillus brevis CH6 36 Lactobacillus sanfranciscensis CH36 7 Lactobacillus casei CH7 37 Bifidobacterium pseudocatenulatum CH37 8 Lactobacillus planantrum CH8 38 Bifidobacterium pseudocatenulatum CH38 9 Lactobacillus sakei CH9 39 Bifidobacterium adolescentis CH39 10 Lactobacillus curvatus CH10 40 Bifidobacterium adol
  • Lactobacillus brevis CH23 is an anaerobic bacilli that show positive gram staining, and shows viability even under aerobic conditions without forming spores.
  • Lactobacillus brevis CH23 survived at 10-42 ° C. and was a stable acid resistant strain at pH 2 for 2 hours.
  • Lactobacillus brevis CH23 survived in 2% sodium chloride solution and actively produced glucosidase.
  • 16S rDNA was measured by the chemical classification of Lactobacillus brevis CH23, and as a result, it was found to have the nucleotide sequence of SEQ ID NO: 1.
  • the 16S rDNA sequence of Lactobacillus brevis CH23 was identified by BLAST search of Genebank (http://www.ncbi.nlm.nih.gov/). As a result, Lactobacillus brevis ( Lactobacillus brevis ) having the same 16S rDNA sequence was identified. Lactobacillus brevis strain was not detected and showed 99% homology with the 16S rDNA subsequence of Lactobacillus brevis strain FJ004.
  • Lactobacillus johnsonii CH32 is an anaerobic bacilli that show positive gram staining, and shows viability even under aerobic conditions without forming spores.
  • Lactobacillus johnsonii CH32 survived stably from 10 °C to 45 °C, was a stable acid resistant strain for 2 hours at pH 2.
  • Lactobacillus johnsonii CH32 actively produced glucosidase, but did not produce beta-glucuronidase.
  • 16S rDNA was determined by the chemical classification of Lactobacillus johnsonii CH32, and as a result, it was found to have the nucleotide sequence of SEQ ID NO: 2.
  • Lactobacillus johnsonii CH32 16S rDNA sequence was identified by BLAST search of Genebank (http://www.ncbi.nlm.nih.gov/), and the Lactobacillus zone having the same 16S rDNA sequence was found.
  • the Sony ( Lactobacillus johnsonii ) strain was not detected and showed 99% homology with the 16S rDNA subsequence of Lactobacillus johnsonii strain JCM 2012.
  • Bifidobacterium longum ( Bifidobacterium longum ) CH57 is an anaerobic bacilli that show positive gram staining, and did not form spores and had very low viability under aerobic conditions.
  • Bifidobacterium longum CH57 was unstable to heat.
  • Bifidobacterium longum CH57 actively produced glucosidase, but did not produce beta-glucuronidase.
  • ronggeom Bifidobacterium (Bifidobacterium longum ) 16S rDNA was determined by chemical classification of CH57, and the result was found to have the nucleotide sequence of SEQ ID NO: 3.
  • Ronggeom Bifidobacterium (Bifidobacterium longum ) 16S rDNA nucleotide sequence of CH57 was identified by BLAST search of Genebank (http://www.ncbi.nlm.nih.gov/) and Bifidobacterium long gum having the same 16S rDNA sequence longum ) was not detected and Bifidobacterium longgum longum ) showed 99% homology with the 16S rDNA subsequence of strain CBT-6.
  • Lactobacillus brevis CH23 shows the physiological characteristics of Lactobacillus brevis CH23, Lactobacillus johnsonii CH32, and Bifidobacterium longum CH57.
  • Table 2 shows the carbon source availability results of Lactobacillus brevis CH23
  • Table 3 shows the carbon source availability results of Lactobacillus johnsonii CH32
  • Table 4 shows the Bifidobacterium long gum. ( Bifidobacterium longum ) shows the results of carbon source availability of CH57.
  • Lactobacillus brevis CH23, Lactobacillus johnsonii CH32 and Bifidobacterium long gum ( Bifidobacterium ) as shown in Tables 2, 3 and 4 below longum ) CH57 has different availability to some carbon sources than strains of the same species.
  • the inventors of the present invention deposited the Lactobacillus brevis CH23 on September 1, 2015 to the Korea Microorganism Conservation Center (address: Yurim Building 45, Hongjenae 2-ga-gil, Seodaemun-gu, Seoul, Korea) on September 1, 2015 and consigned KCCM 11762P. I am assigned a number.
  • the inventors of the present invention patented Lactobacillus johnsonii CH32 to the Korea Microbiological Conservation Center (address: 45 Yurim Building 45 Hongjenae 2-ga-gil, Seodaemun-gu, Seoul, Korea) on September 1, 2015 KCCM
  • the accession number was 11763P.
  • DPPH (2,2-Diphenyl-1-picrylhydrazyl) was dissolved in ethanol to a concentration of 0.2 mM to prepare a DPPH solution.
  • 0.1 mL of the DPPH solution was added to lactic acid bacteria suspension (1 ⁇ 10 8 CFU / mL) or vitamin C solution (1 g / mL) and incubated at 37 ° C. for 20 minutes.
  • the culture was centrifuged at 3000 rpm for 5 minutes to obtain a supernatant. Thereafter, the absorbance of the supernatant was measured at 517 nm, and the antioxidant activity of the lactic acid bacteria was calculated.
  • E. coli from the elderly Esherichia coli ), Krebciela New Monia ( Klebsiella pneumoniae ), Proteus Mirabilis ( Proteus mirabilis Pathogens) were isolated and incubated. Then, pathogens (1 ⁇ 10 each) in 10 ml of sterile general anaerobic medium (GAM medium, Nissui Pharmaceutical, Japan) 5 CFU) and lactic acid bacteria (1 ⁇ 10) 5 CFU) were transplanted and incubated anaerobicly for 24 hours. Thereafter, the culture solution was sonicated for about 1 hour to destroy the outer membrane of bacteria, and centrifuged at 5000 ⁇ g to obtain a supernatant.
  • GAM medium sterile general anaerobic medium
  • lactic acid bacteria (1 ⁇ 10) 5 CFU
  • the content of the representative endotoxin LPS (lipopolysaccharide) present in the supernatant was measured by LAL (Limulus Amoebocyte Lysate) assay kit (manufacturer: Cape Cod Inc., USA).
  • LAL Limulus Amoebocyte Lysate
  • the culture solution obtained through the same experiment was diluted 1000 times and 100,000 times, and then cultured in DHL medium, and the number of E. coli, Krebs. It was.
  • Caco2 cells cultured in the Korean Cell Line Bank were incubated for 48 hours in RPMI 1640 medium, and then Caco2 cell cultures were dispensed into 12-well plates to 2 ⁇ 10 6 cells per well. Thereafter, each well was treated with 1 ⁇ g of LPS (lipopolysaccharide) alone or 1 ⁇ g of LPS (lipopolysaccharide) and lactic acid bacteria (1 ⁇ 10 4 CFU / mL), followed by incubation for 24 hours. Then, cells cultured from each well were scraped, and the expression level of tight junction protein ZO-1 was measured by immunoblotting.
  • LPS lipopolysaccharide
  • lactic acid bacteria 1 ⁇ 10 4 CFU / mL
  • SH-SY5Y cells distributed from the Korean Cell Line Bank were cultured in DMEM medium with 10% FBS and 1% antibiotics, and dispensed into 12-well plates to 2 ⁇ 10 6 cells per well. Then, LPS (lipopolysaccharide) isolated from Proteus mirabilis together with lactic acid bacteria (1 ⁇ 10 4 CFU / mL) was added to each well at a concentration of 0.2 mg / mL, followed by incubation, followed by NF- ⁇ B ( The level of inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells and the expression level of alpha-synuclein were measured by immunoblotting. NF- ⁇ B is known to cause tissue damage and aging-related diseases such as Alzheimer's disease, and alpha-synuclein is known to cause Parkinson's disease.
  • Bifidobacterium pseudo Carthage press ratum (Bifidobacterium pseudocatenulatum) CH38 ronggeom
  • Bifidobacterium (Bifidobacterium longum ) CH57 lactic acid bacteria have excellent antioxidant activity, strongly inhibited lipopolysaccharide (LPS) production and beta-glucuronidase activity, and strongly induced tight junction protein expression. It strongly inhibited the activation of NF- ⁇ B and strongly inhibited the expression of alpha-synuclein.
  • LPS lipopolysaccharide
  • the lactic acid bacteria have an excellent inhibitory effect on the enzymatic activity of the enterobacteriaceae bacteria related to the antioxidant effect, inflammation and carcinogenesis, and inhibit the production of LPS (lipopolysaccharide), an endotoxin produced by the harmful bacteria of the intestinal flora, By inducing the expression of (tight junction protein) can improve the intestinal permeability (Intestinal permeability).
  • LPS lipopolysaccharide
  • an endotoxin of intestinal microorganisms K. pneumoniae , E. coli , P. mirabilis
  • Alzheimer's disease or Parkinson's disease as well as activation or production of neurodegenerative substances.
  • Inhibition can improve Alzheimer's disease and Parkinson's disease.
  • the lactic acid bacteria are expected to have a synergistic effect through various actions such as improvement of intestinal leak syndrome, inhibition of endotoxin production, activation or inhibition of neurodegeneration causing substances.
  • 13 lactic acid bacteria were selected as a lactic acid bacterium for the effect of cognitive improvement.
  • the first space and the second space are divided into two spaces, and a guillotine-type doorway is formed between the two spaces, and the first space and the second space are connected through the doorway.
  • the first space was kept bright using illumination and the second space was kept dark.
  • the bottom of the second space, which is kept dark, is provided with a lattice, and when the experimental animal moves to the dark space, an electric shock of 0.5 mA flows through the grid of the floor for 3 seconds.
  • mice in the 13 selected lactic acid bacteria were suspended in physiological saline at a concentration of 1 ⁇ 10 10 CFU / ml, and then 0.1 ml (lactic acid bacteria 1 ⁇ 10) was used daily in experimental animals (male ICR mice, 5 weeks old, purchased from Raonbio). Corresponding to 9 CFU) for 3 days.
  • mice in the normal group and the memory impaired group were administered with saline 0.1 ml each day for 3 days.
  • the mice corresponding to the positive control group was dosed with a positive control drug donepezil (Alzheimer's disease and Alzheimer's type dementia) daily at a dose of 5 mg / kg (body weight) for 3 days.
  • the number of mice per experimental group was nine.
  • mice On the second day of drug administration, the mice were placed in the first space that remained bright, and after about 20 seconds of exploration time, the guillotine-type doorway was opened to allow the mice to enter the second space that remained dark. . At this time, mice that did not move to the second space that remained dark until 60 seconds after opening of the guillotine-type entrance were excluded from the experiment. Once the mouse enters the darkened second space, the guillotine-type doorway closes, a 0.5-kV electric shock flows through the bottom grid for 3 seconds, and the mouse remembers this electric shock.
  • mice in each experimental group measured the latency time (latency time) to open the guillotine door after 4 seconds of 10 seconds and enter the dark side up to 300 seconds, and the results are shown in Table 8 below. In Table 8 below, the longer the latency time, the better learning of passive avoidance and short-term memory recovery.
  • Lactobacillus brevis CH23, Lactobacillus johnsonii CH32, or Bifidobacterium in cognitive impairment or memory impairment induced by scopolamine The longum CH57 was significantly increased in delay time compared to the memory impaired group treated with scopolamine alone, especially when Lactobacillus johnsonii CH32 was administered compared with the donepezil, which is a commercial treatment. It showed excellent effect.
  • the instrument used for the Y-maze test consists of three branches, each branch is 42cm long, 3cm wide and 12cm high, and the angle of each branch is 120 ° and made of black polyvinyl resin. .
  • mice in the 13 selected lactic acid bacteria were suspended in physiological saline at a concentration of 1 ⁇ 10 10 CFU / ml, and then 0.1 ml (lactic acid bacteria 1 ⁇ 10) was used daily in experimental animals (male ICR mice, 5 weeks old, purchased from Raonbio). Corresponding to 9 CFU) for 3 days.
  • mice in the normal group and the memory impaired group were administered with saline 0.1 ml each day for 3 days.
  • the mice corresponding to the positive control group was dosed with a positive control drug donepezil (Alzheimer's disease and Alzheimer's type dementia) daily at a dose of 5 mg / kg (body weight) for 3 days.
  • the number of mice per experimental group was nine.
  • Experiment group Alteration behavior (unit:%) Normal 74.5 Memory impairment treated with scopolamine only 49.9 Positive control treated with scopolamine and donepezil 65.8 Scopolamine and Lactobacillus acidophilus CH3 treatment group 53.7 Scopolamine and Lactobacillus curvatus CH5 treatment group 51.3 Scopolamine and Lactobacillus sakei CH11 treatment group 49.0 Scopolamine and Lactobacillus fermentum CH15 treatment group 56.2 Scopolamine and Lactobacillus johnsonii CH21 treatment group 53.5 Scopolamine and Lactobacillus brevis CH23 treatment group 59.2 Scopolamine and Lactobacillus johnsonii CH32 treatment group 63.9 Scopolamine and Lactobacillus plantarum CH35 treatment group 52.4 Scopolamine and Bifidobacterium pseudocatenulatum CH38 treatment group 52.5 Scopolamine and Bifidobacterium adolescentis CH41 treatment group 54.1 Scopolamine and Bifidobacterium longum CH56
  • Lactobacillus brevis CH23, Lactobacillus johnsonii CH32, or Bifidobacterium in model animals in which cognitive impairment or memory impairment was induced by scopolamine.
  • Administration of longum CH57 significantly increased altered behavior compared to memory impairment group treated with scopolamine alone, especially in the case of Lactobacillus johnsonii CH32, which is equivalent to the administration of donepezil, which is a commercial treatment.
  • Level showed excellent effect.
  • Lactobacillus johnsonii CH32 cells were cultured in an edible TS medium and centrifuged (10,000 g f , 20 minutes) to obtain Lactobacillus johnsonii CH32 cells.
  • the obtained Lactobacillus johnsonii CH32 cells were washed twice with physiological saline and suspended in 100 ml to prepare a suspension of Lactobacillus johnsonii CH32 cells.
  • 10 g of finely ground red beans were added to 90 ml of Lactobacillus johnsonii CH32 cell suspension and incubated for 24 hours to ferment the red beans. Thereafter, the red bean fermentation broth was lyophilized to obtain a red bean fermented product.
  • the red bean suspension is prepared by suspending red bean powder in saline solution and the daily dose is 0.2g per mouse based on red bean powder
  • Lactobacillus johnsonii CH32 was suspended in physiological saline and the daily dose was 2 ⁇ 10 8 CFU per mouse based on Lactobacillus johnsonii CH32.
  • the red bean fermented product was suspended in physiological saline, and the daily dose was 0.2g per mouse based on the red bean fermented product, and 0.2g red bean fermented product contained about 2 ⁇ 10 8 CFU of Lactobacillus johnsonii CH32.
  • the Y-maze experiment was performed in the same manner as described above except that the drug and the dose were administered, and the results are shown in Table 11 below.
  • Table 11 the administration of red bean suspension or Lactobacillus johnsonii CH32 (daily dose: 2 ⁇ 10 8 CFU / mouse) to mice did not significantly improve impaired memory, but when the red bean fermented product was administered Significantly improved impaired memory.
  • Experiment group Alteration behavior (unit:%) Normal 75.2 Memory impairment treated with scopolamine only 45.4 Positive control treated with scopolamine and donepezil 63.2 Group treated with scopolamine and red bean suspension 1 ) 52.4 Scopolamine and Lactobacillus johnsonii CH32 treatment group 2 ) 57.6 Scopolamine and red bean fermented products 3 ) Treatment group 63.3
  • the red bean suspension is prepared by suspending red bean powder in saline solution and the daily dose is 0.2g per mouse based on red bean powder
  • Lactobacillus johnsonii CH32 was suspended in physiological saline and the daily dose was 2 ⁇ 10 8 CFU per mouse based on Lactobacillus johnsonii CH32.
  • the red bean fermented product was suspended in physiological saline, and the daily dose was 0.2g per mouse based on the red bean fermented product, and 0.2g red bean fermented product contained about 2 ⁇ 10 8 CFU of Lactobacillus johnsonii CH32.
  • Escherichia coli isolated from animals with impaired memory coli ) K20 strain was administered to mice to induce memory impairment, and the effect of improving the cognitive ability of lactic acid bacteria was measured through the Y-maze test and the passive avoidance test.
  • Escherichia coli K20 strains were administered to the mice (male ICR mice, 20-21 g, 5 weeks old, purchased from Raonbio) adapted for 1 week in an animal laboratory in an amount of 1 ⁇ 10 9 CFU once daily for 5 days. Memory impairment was induced.
  • the normal group was administered saline instead of E. coli K20 strain.
  • 0.1 ml of lactic acid bacteria suspension lactic acid bacteria suspended in physiological saline at a concentration of 1 ⁇ 10 10 CFU / ml
  • mice with memory impairment from the day after the last dose of E. coli K20 strain (lactic acid bacteria 1 ⁇ 10 9) Corresponding to CFU) for 5 days.
  • mice in the normal group and the memory impaired induction group were administered with saline 0.1 ml daily for 5 days.
  • lactic acid bacteria suspension lactic acid bacteria were suspended in physiological saline at a concentration of 1 ⁇ 10 10 CFU / ml
  • mice corresponding to the normal group by 0.1 ml (corresponding to lactic acid bacteria 1 ⁇ 10 9 CFU) for 5 days. This was used as a positive control.
  • the number of mice per experimental group was nine.
  • mice On the second day of drug administration, the mice were placed in a brightly maintained first space of the passive evacuation device, and after about 20 seconds of searching time, the guillotine-type entrance was opened to the second space where the mice were kept dark. I was able to enter. At this time, mice that did not move to the second space that remained dark until 60 seconds after opening of the guillotine-type entrance were excluded from the experiment. Once the mouse enters the darkened second space, the guillotine-type doorway closes, a 0.5-kV electric shock flows through the bottom grid for 3 seconds, and the mouse remembers this electric shock.
  • mice in each experimental group measured the latency time (latency time) to open the guillotine door and enter all four rounds in the dark to 300 seconds.
  • hippocampus was isolated from the mice in each experimental group, and the expression levels of brain-derived neurotrophic factor (BDNF), known as nerve growth promoter, and cyclic AMP, known as memory enhancing transcription factor. The activation level of response element-binding protein) was measured.
  • BDNF brain-derived neurotrophic factor
  • cyclic AMP cyclic AMP
  • FIG. 1 is a graph showing the effect of Lactobacillus johnsonii CH32 administration on the Y-maze test of a model animal induced memory impairment by Escherichia coli K20 strain.
  • Figure 2 shows that administration of Lactobacillus johnsonii CH32 is Escherichia coli ) is a graph showing the effect on the passive avoidance test of a model animal induced memory impairment by the K20 strain.
  • Figure 3 shows the administration of Lactobacillus johnsonii CH32 is Escherichia coli ) is a photograph showing the effect on the expression level of neuronal growth promoters in model animals induced memory impairment by K20 strain.
  • NOR represents a normal group
  • NOR + CH32 represents an experimental group in which Lactobacillus johnsonii CH32 is administered to a normal group
  • EC represents Escherichia. coli
  • EC + CH32 is Escherichia coli. coli
  • K20 strain was treated to induce memory impairment
  • Lactobacillus johnsonii Lactobacillus johnsonii
  • FIGS. 1 to 3 when Lactobacillus johnsonii CH32 was administered to the normal group, memory was slightly present, but there was no significance.
  • Proteus Mirabilis Proteus mirabilis Cognitive Improving Effects of Lactic Acid Bacteria Using Model Animals Induced by Memory Impairment
  • Proteus mirabilis K21 strain isolated from memory impaired animals was administered to mice to induce memory impairment (similar to the symptoms of Parkinson's disease), and through the Y-maze test The effect of improving cognitive ability was measured.
  • mice were acclimated for 1 week in an animal lab in Proteus (male ICR mice, 20-21 g, 5 weeks old, purchased from Raonbio) Mira Billy's (Proteus mirabilis ) K21 strain was administered once daily for 5 days in an amount of 1 ⁇ 10 9 CFU to induce memory impairment.
  • Proteus Mirabilis Proteus mirabilis
  • Physiological saline was administered instead of K21 strain.
  • Lactobacillus suspension lactic acid bacteria was added to physiological saline at a concentration of 1 ⁇ 10 10 CFU / ml) in mice with induced memory impairment (male ICR mice, 5 weeks old, purchased from Raonbio). Suspended) daily 0.1 ml (corresponding to lactic acid bacteria 1 ⁇ 10 9 CFU) for 5 days. In addition, mice in the normal group and the memory impaired induction group were administered with saline 0.1 ml daily for 5 days.
  • mice corresponding to the positive control group was dosed with a positive control drug donepezil (Alzheimer's disease and Alzheimer's disease treatment) at a dose of 5 mg / kg (body weight) for 5 days.
  • the number of mice per experimental group was nine.
  • Experiment group Alteration behavior (unit:%) Normal 73.8 Proteus memory damage induction group treated with mirabilis K21 46.4 Proteus positive control group treated with mirabilis K21 strain and donepezil 58.6 Proteus mirabilis K21 strain and Lactobacillus acidophilus CH3 treated group 52.5 Proteus mirabilis K21 strain and Lactobacillus curvatus CH5 treatment group 50.2 Proteus mirabilis K21 strain and Lactobacillus sakei CH11 treatment group 50.7 Proteus mirabilis K21 strain and Lactobacillus fermentum CH15 treatment group 55.5 Proteus mirabilis K21 strain and Lactobacillus johnsonii CH21 treatment group 54.7 Proteus mirabilis K21 strain and Lactobacillus brevis CH23 treatment group 53.3 Proteus mirabilis K21 strain and Lactobacillus johnsonii CH32 treatment group 62.8 Proteus mirabilis K21 strain and Lactobacillus plantarum CH
  • Lactobacillus johnsonii CH32 is administered to a model animal in which memory impairment is induced by the Proteus mirabilis K21 strain, it is more effective than the administration of donepezil, which is used as a commercial treatment. It showed a better effect.

Abstract

La présente invention concerne un nouveau lactobacillus et une utilisation de celui-ci, le lactobacillus étant isolé à partir de kimchi et, par conséquent, très sûr, et présentant divers types d'activité biologique, telle qu'une activité d'amélioration de la mémoire, une activité d'induction de l'expression de la protéine de jonction serrée, une activité anti-oxydation, une activité de suppression de la génération de lipopolysaccharide (LPS), et une activité inhibitrice de la β-glucuronidase. Le nouveau lactobacillus selon la présente invention peut être utilisé comme alicament pour prévenir, atténuer ou traiter des maladies cérébrales dégénératives ou des troubles de la fonction cognitive.
PCT/KR2016/009961 2015-09-15 2016-09-06 Nouveau lactobacillus et composition pour prévenir, atténuer ou traiter des maladies cérébrales dégénératives ou des troubles de la fonction cognitive WO2017047962A1 (fr)

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CN201680066260.6A CN108603162B (zh) 2015-09-15 2016-09-06 预防、改善或治疗退行性脑病或认知功能障碍的新型乳酸菌和组合物
EP16846783.5A EP3351616A4 (fr) 2015-09-15 2016-09-06 Nouveau lactobacillus et composition pour prévenir, atténuer ou traiter des maladies cérébrales dégénératives ou des troubles de la fonction cognitive
US15/759,928 US10471111B2 (en) 2015-09-15 2016-09-06 Lactobacillus and composition for preventing, improving, or treating degenerative brain diseases or cognitive function disorders
JP2018513764A JP6626569B2 (ja) 2015-09-15 2016-09-06 新規乳酸菌および変性脳疾患または認知機能障害の予防、改善または治療のための組成物
CA2998877A CA2998877C (fr) 2015-09-15 2016-09-06 Souche de lactobacilles johnsonii et son utilisation pour la prevention et le traitement de maladies degeneratives du cerveau ou de troubles de la fonction cognitive
NZ741028A NZ741028A (en) 2015-09-15 2016-09-06 Novel lactobacillus and composition for preventing, improving, or treating degenerative brain diseases or cognitive function disorders
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AU2016324846A AU2016324846B2 (en) 2015-09-15 2016-09-06 Novel lactobacillus and composition for preventing, improving, or treating degenerative brain diseases or cognitive function disorders
HK18113645.2A HK1254665A1 (zh) 2015-09-15 2018-10-24 預防、改善或治療退行性腦病或認知功能障礙的新型乳酸菌和組合物

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CN111655839B (zh) * 2017-11-20 2023-01-20 庆熙大学校产学协力团 新型乳酸菌及其用途
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US11672838B2 (en) 2020-06-16 2023-06-13 Md Healthcare Inc. Composition for prevention or treatment of neurological or mental disorders comprising extracellular vesicles derived from Lactobacillus paracasei
WO2022139425A1 (fr) * 2020-12-21 2022-06-30 경희대학교 산학협력단 Procédé de diagnostic de maladies neurodégénératives par l'utilisation de l'hpma
CN114886929A (zh) * 2022-04-29 2022-08-12 河北一然生物科技股份有限公司 两歧双歧杆菌b11在制备改善脑部认知功能、提高记忆力产品中的应用
CN114886929B (zh) * 2022-04-29 2022-11-22 河北一然生物科技股份有限公司 两歧双歧杆菌b11在制备改善脑部认知功能、提高记忆力产品中的应用

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