WO2017145415A1 - Agent favorisant le développement d'immunité - Google Patents

Agent favorisant le développement d'immunité Download PDF

Info

Publication number
WO2017145415A1
WO2017145415A1 PCT/JP2016/075071 JP2016075071W WO2017145415A1 WO 2017145415 A1 WO2017145415 A1 WO 2017145415A1 JP 2016075071 W JP2016075071 W JP 2016075071W WO 2017145415 A1 WO2017145415 A1 WO 2017145415A1
Authority
WO
WIPO (PCT)
Prior art keywords
immune development
raffinose
lactulose
bifidobacterium breve
cells
Prior art date
Application number
PCT/JP2016/075071
Other languages
English (en)
Japanese (ja)
Inventor
達弥 江原
和泉　裕久
毅 松原
Original Assignee
森永乳業株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 森永乳業株式会社 filed Critical 森永乳業株式会社
Priority to JP2018500972A priority Critical patent/JP6773368B2/ja
Publication of WO2017145415A1 publication Critical patent/WO2017145415A1/fr
Priority to PH12018501822A priority patent/PH12018501822A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
    • A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
    • 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
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7016—Disaccharides, e.g. lactose, lactulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • 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
    • 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

Definitions

  • the present invention relates to an immune development promoter.
  • Non-patent Document 1 Bifidobacterium breve and Lactobacillus rhamnosus have been reported to be effective for inflammation in chronic asthmatic model mice.
  • Non-patent Document 1 Bifidobacterium longum ATCC BAA-999 and / or Bifidobacterium breve LMG23729 can prevent allergic diseases in infants.
  • Non-patent Document 2 Indigestible oligosaccharides have been reported to have an immunomodulatory action on human monocyte-derived dendritic cells (Non-patent Document 3). Furthermore, a bifidobacteria growth promoting composition containing lactulose, fructooligosaccharide and / or galactooligosaccharide, and raffinose as active ingredients is known (Patent Document 2).
  • Bifidobacterium breve and scFOS short chain fructooligosaccharides
  • lcFOS long chain fructooligosaccharides
  • ADS pectin-derived acidic-oligosaccharides: pectin-derived acidic oligosaccharides
  • JP 2014-065669 A Japanese Patent Laid-Open No. 10-175867
  • An object of the present invention is to provide a technique for promoting immune development.
  • the present inventors have found that when a mammal is ingested with Bifidobacterium breve, lactulose, raffinose, and galactooligosaccharide, immune development can be promoted, and the present invention has been completed.
  • the present invention provides an immune development promoter comprising bacteria belonging to Bifidobacterium breve, lactulose, raffinose, and galactooligosaccharide.
  • the above-mentioned immunodevelopment promoting agent is preferably characterized in that the promotion of immune development is the promotion of an increase in the number of T cells.
  • the above-mentioned immunity development promoter has a preferred embodiment in which the bacterium is Bifidobacterium breve M-16V (LMG23729).
  • the immune development promoter preferably has a weight ratio of lactulose, raffinose, and galactooligosaccharide of 1 to 9: 1 to 9: 1 to 9.
  • the immune development promoting agent is preferably configured such that the amount of the bacteria is 1 ⁇ 10 6 to 1 ⁇ 10 12 cfu with respect to 1 g of the total amount of lactulose, raffinose and galactooligosaccharide.
  • the present invention also provides a feed containing the above-mentioned immune development promoter.
  • the present invention also provides a food and drink composition for promoting immune development, comprising as an active ingredient a bacterium belonging to Bifidobacterium breve, lactulose, raffinose, and galactooligosaccharide.
  • the said food-drinks composition makes it a preferable aspect that a food-drinks composition is a health functional food.
  • the immune development promoter of the present invention contains bacteria belonging to Bifidobacterium breve and three types of oligosaccharides: lactulose, raffinose, and galactooligosaccharide.
  • Bacteria belonging to Bifidobacterium breve are not particularly limited as long as they can promote immune development when ingested together with lactulose, raffinose, and galactooligosaccharides by mammals. Brave M-16V (LMG23729) and the like.
  • the bacteria are Belgian Coordinated Collections of microorganisms (BCCM) (http://bccm.belspo.be/, Universiteit Gent, Laboratorium voor Microbiologie, KL Ledeganckstraat, Belgian Coordinated Collections of Microorganisms 35 9000 Gent Belgium) is stored as a public deposit and can be obtained from the same organization under the strain number of LMG23729.
  • Bifidobacterium breve M-16V is not limited to the deposited bacteria, and may be a bacterium substantially equivalent to the deposited bacteria.
  • Bacteria substantially equivalent to the above-mentioned deposited bacteria are bacteria belonging to Bifidobacterium breve and can promote immune development when ingested together with lactulose, raffinose, and galactooligosaccharides.
  • the base sequence of the 16S rRNA gene preferably has 99.86% or more, more preferably 99.93% or more, more preferably 100% homology to the base sequence of the 16S rRNA gene of the deposited bacterium.
  • a bacterium having the same bacteriological properties as the above-mentioned deposited bacterium preferably a bacterium having the same bacteriological properties as the above-mentioned deposited bacterium.
  • Bifidobacterium breve M-16V includes mutants and genetically modified strains having the same bacterium as a
  • Bacteria belonging to Bifidobacterium breve may be bacterial cells or a culture containing the cells. Bacteria may be live or dead, and may be both live and dead, but are preferably live. In addition, various additional operations such as freeze-drying can be performed after the culture as long as the effects of the present invention are not impaired. The additional operation is preferably one in which viability of viable bacteria is high.
  • Bacteria belonging to Bifidobacterium breve can be easily propagated by culturing the bacteria.
  • the method of culturing is not particularly limited as long as the bacterium can grow, and the method usually used for culturing Bifidobacterium (Bifidobacteria) can be appropriately modified as necessary.
  • the culture temperature may be 25 to 50 ° C., preferably 30 to 40 ° C.
  • the culture is preferably performed under anaerobic conditions, and for example, the culture can be performed while anaerobic gas such as carbon dioxide gas is passed.
  • the medium used for the culture is not particularly limited, and a medium usually used for culture of Bifidobacterium can be appropriately modified as necessary. That is, as the carbon source, for example, saccharides such as galactose, glucose, fructose, mannose, cellobiose, maltose, lactose, sucrose, trehalose, starch, starch hydrolyzate, and molasses can be used according to the utilization.
  • the nitrogen source for example, ammonium salts such as ammonia, ammonium sulfate, ammonium chloride, and ammonium nitrate, and nitrates can be used.
  • inorganic salts examples include sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, and ferrous sulfate.
  • Organic components such as peptone, soybean powder, defatted soybean meal, meat extract, yeast extract and the like may also be used.
  • an MRS medium can be preferably used as the prepared medium.
  • Lactulose is a disaccharide composed of fructose and galactose (4-O- ⁇ -D-galactopyranosyl-D-fructose, Gal ⁇ 1-4 Fru), and is known in the art, for example, JP-A-3-169888. And by the method described in JP-A-6-228179.
  • a commercial product for example, manufactured by Morinaga Milk Industry Co., Ltd.
  • Raffinose is a trisaccharide ( ⁇ -D-fructofuranosyl- ⁇ -D-galactopyranosyl- (1-6) - ⁇ -D-glucopyranoside, Gal ⁇ 1 bound to fructose, galactose and glucose one by one. -6 Glc ⁇ 1-2 ⁇ Fru) and described in known methods such as “Food New Material Effective Utilization Technology Series No. 6,“ Raffinose ”, page 2, Confectionery Technology Center, 1996”. It can be manufactured by the method. For raffinose, a commercially available product (for example, manufactured by Nippon Sugar Sugar Co., Ltd.) can also be used.
  • Galacto-oligosaccharide is an oligosaccharide having a structure represented by Gal- (Gal) n-Glc (n is 1 to 3, ⁇ -1,4 bond or ⁇ -1,6 bond) or a mixture thereof.
  • Galactooligosaccharides are industrially produced by transfer reaction with ⁇ -galactosidase using lactose as a raw material, and the main component is 4′-galactosyl lactose (4′-GL), which is a trisaccharide in which one galactose is bonded to the non-reducing end of lactose. ).
  • As the galactooligosaccharide a commercially available product (for example, manufactured by Yakult Pharmaceutical Co., Ltd.) can also be used.
  • the galactooligosaccharide may be one kind or a mixture of two or more kinds.
  • Bacteria belonging to Bifidobacterium breve and compositions containing lactulose, raffinose, and galactooligosaccharide can be widely used as medicines, foods and drinks, and feeds.
  • a drug for promoting immune development a food and drink for promoting immune development, a food and drink composition for promoting immune development, a health functional food for promoting immune development, and a feed for promoting immune development can be provided.
  • the drug of the present invention is not particularly limited as long as it contains bacteria belonging to Bifidobacterium breve, and lactulose, raffinose, and galactooligosaccharide.
  • the agent of the present invention may be a bacterium belonging to Bifidobacterium breve, as well as lactulose, raffinose, and galactooligosaccharide, and may be formulated by blending a physiologically acceptable liquid or solid pharmaceutical carrier. May be used.
  • Bacteria belonging to Bifidobacterium breve, lactulose, raffinose, and galactooligosaccharide may be formulated as a single body, or may be separately formulated into two or three or more drugs.
  • the preparation form of the drug of the present invention is not particularly limited, and tablets (including sugar-coated tablets, enteric-coated tablets, buccal tablets), powders, capsules (including enteric capsules, soft capsules), granules (coated ones) ), Pills, troches, encapsulated liposomes, solutions, or pharmaceutically acceptable sustained-release preparations thereof.
  • tablets including sugar-coated tablets, enteric-coated tablets, buccal tablets
  • powders including enteric capsules, soft capsules), granules (coated ones)
  • Pills including sugar-coated tablets, enteric capsules, soft capsules), granules (coated ones)
  • Pills including sugar-coated tablets, enteric capsules, soft capsules
  • granules coated ones
  • a bacterium belonging to Bifidobacterium breve, and lactulose, raffinose, and galactooligosaccharide, a known or future-found drug having an immune development promoting action may use together with a pharmaceutical composition.
  • the pharmaceutical composition to be used in combination may be contained as one of the active ingredients in the drug of the present invention, or may be combined and commercialized as a separate drug without being contained in the drug of the present invention.
  • Carriers and excipients used in the above formulations include lactose, glucose, sucrose, mannitol, potato starch, corn starch, calcium carbonate, calcium phosphate, calcium sulfate, crystalline cellulose, licorice powder, gentian powder and the like as binders
  • binders for example, starch, gelatin, syrup, polyvinyl alcohol, polyvinyl ether, polyvinyl pyrrolidone, hydroxypropyl cellulose, ethyl cellulose, methyl cellulose, carboxymethyl cellulose and the like can be exemplified.
  • disintegrant examples include starch, agar, gelatin powder, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, crystalline cellulose, calcium carbonate, sodium hydrogen carbonate, sodium alginate and the like.
  • magnesium stearate magnesium stearate, hydrogenated vegetable oil, polyethylene glycol, etc.
  • colorant red No. 2, yellow No. 4, and blue No. 1, etc. that are allowed to be added to pharmaceuticals, etc. It can be illustrated.
  • Tablets and granules include sucrose, hydroxypropylcellulose, purified shellac, gelatin, sorbitol, glycerin, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, cellulose phthalate acetate, hydroxypropylmethylcellulose phthalate, methyl methacrylate, It can also be coated with a methacrylic acid polymer or the like.
  • Another aspect of the present invention is the use of bacteria belonging to Bifidobacterium breve, and lactulose, raffinose, and galactooligosaccharides in the manufacture of a medicament for promoting immune development.
  • Another aspect of the present invention is a bacterium belonging to Bifidobacterium breve used for promoting immune development, and lactulose, raffinose, and galactooligosaccharide.
  • Another aspect of the present invention is a method of promoting immune development, comprising administering a bacterium belonging to Bifidobacterium breve, lactulose, raffinose, and galactooligosaccharide, or a drug of the present invention to a mammal.
  • Another aspect of the present invention is to prevent or treat a disease that can be prevented or treated by promoting immune development, wherein a bacterium belonging to Bifidobacterium breve and lactulose, raffinose, and galactooligosaccharide are administered to a mammal.
  • a bacterium belonging to Bifidobacterium breve and lactulose, raffinose, and galactooligosaccharide are administered to a mammal.
  • Mammals include humans, cows, sheep, goats, pigs, dogs, cats, horses and the like.
  • the amount of bacteria belonging to Bifidobacterium breve contained in the drug of the present invention is appropriately set according to the dosage form, usage, age of subject, sex, type of disease, degree of disease, and other conditions. Is preferably within the range of 1 ⁇ 10 6 to 1 ⁇ 10 12 cfu / g or 1 ⁇ 10 6 to 1 ⁇ 10 12 cfu / ml, preferably 1 ⁇ 10 7 to 1 ⁇ 10 11 cfu / g. Or, it is more preferably in the range of 1 ⁇ 10 7 to 1 ⁇ 10 11 cfu / ml. If the bacterium is dead, cfu / g or cfu / ml can be replaced with individual cells / g or individual cells / ml. “Cfu” represents a colony forming unit.
  • the amount of bacteria belonging to Bifidobacterium breve is 1 ⁇ 10 6 to 1 ⁇ 10 12 cfu, preferably 1 ⁇ 10 7 to 1 ⁇ 10, per 1 g of the total amount of lactulose, raffinose and galactooligosaccharide. It is preferably 12 cfu, more preferably 1 ⁇ 10 8 to 1 ⁇ 10 12 cfu.
  • the weight ratio of lactulose, raffinose and galactooligosaccharide is 1 to 9: 1 to 9: 1 to 9, preferably 2 to 8: 2 to 8: 2 to 8, more preferably 3 to 7: 3 to 7. : It is preferably 3-7.
  • the drug of the present invention is useful for promoting the immune development of mammals.
  • Immunity develops as the animal grows after birth. Promoting immune development includes both speeding up the development of such immunity and increasing the degree of immunity development. In addition, promotion of immune development includes promotion of increase in the number of T cells.
  • T cells Foxp3 positive cells, that is, regulatory T cells (regulatory T cells, Treg), which are one of helper T cells that suppress excessive immune responses, increase in the number of cells as they grow and occupy T cells. The ratio also tends to increase.
  • the agent of the present invention can accelerate the increase in the number of regulatory T cells or promote the increase in the number of regulatory T cells. Therefore, in the present specification, “stimulation of immune development” can be replaced by “an increase in Foxp3 positive cells” or “an increase in regulatory T cells”.
  • R17 is a RORgt positive cell, ie, Th17 cell, which is one of inflammation-inducing helper T cells characterized by high production of IL-17.
  • Th17 cell which is one of inflammation-inducing helper T cells characterized by high production of IL-17.
  • the agent of the present invention can accelerate the increase in the number of Th17 cells or increase the number of Th17 cells. Therefore, in the present specification, “stimulation of immune development” can be replaced with “increased RORgt positive cells” or “increased Th17 cells”.
  • Immuno development promotion can be replaced with “an increase in at least one of Foxp3-positive cells, regulatory T cells, RORgt-positive cells, and Th17 cells”.
  • the present invention can increase regulatory T cells that suppress an excessive immune reaction during immune development, such as Foxp3-positive cells. Therefore, diseases for which the drug of the present invention is effective, or diseases or symptoms that can be prevented or treated by promoting immune development include autoimmune diseases, allergic diseases, rejection reactions, infections, diseases derived from adipose tissue inflammation, etc. Diseases caused by such an excessive immune reaction can be mentioned.
  • Autoimmune diseases include scleroderma dermatitis, sarcoidosis, atherosclerosis, disseminated intravascular coagulation syndrome, Kawasaki disease, Graves disease (Graves' disease), nephrotic syndrome, chronic fatigue syndrome, Wegener's granulomatosis, Henoch Shaneline purpura, microscopic vasculitis in the kidney, chronic active hepatitis, uveitis, septic shock, toxic shock syndrome, septic syndrome, cachexia, AIDS (acquired immune deficiency syndrome), acute crossing Myelitis, Huntington's disease, Parkinson's disease, Alzheimer's disease, stroke, primary biliary cirrhosis, hemolytic anemia, multiglandular dysfunction syndrome type 1, multiglandular dysfunction syndrome type 2, Schmidt syndrome, adult ( Acute) respiratory distress syndrome, alopecia, alopecia areata, seronegative arthropathy, arthropathy, Reiter's disease, psoriatic arthropathy
  • Allergic diseases include atopic dermatitis, atopic allergy, food allergy, pollen allergy, allergic rhinitis (pollen allergy), anaphylaxis, pet allergy, latex allergy, drug allergy, allergic rhinitis conjunctivitis, eosinophilic esophagitis , Eosinophilia syndrome, eosinophilic gastroenteritis and the like.
  • rejection examples include graft versus host rejection.
  • Infectious diseases include Salmonella, Shigella, Clostridium difficile, Mycobacterium (tuberculosis as disease), protozoa (malaria as disease), filamentous nematodes (filariasis as disease), schistosomiasis (as disease) Schistosomiasis), toxoplasma (toxoplasmosis as disease), leishmania (leishmaniasis as disease), HCV and HBV (hepatitis C and hepatitis B as disease), herpes simplex virus (herpes as disease) Infectious diseases due to such as.
  • Diseases derived from adipose tissue inflammation include metabolic syndrome, visceral obesity, insulin resistance, hyperglycemia, dyslipidemia, hypertriglycerideemia, low HDL cholesterolemia, increased blood pressure, arteriosclerotic disease, type 2 diabetes, Nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), etc. are mentioned.
  • the dose of the drug of the present invention can be appropriately selected depending on the age, sex, condition, other conditions, etc. of the administration subject.
  • the amount of bacteria belonging to Bifidobacterium breve is preferably 2 ⁇ 10 4 to 2 ⁇ 10 9 cfu / kg / day, more preferably 2 ⁇ 10 6 to 2 ⁇ 10 9 cfu / kg / day. It is good to use the amount to become a standard.
  • the administration time of the drug of the present invention is not particularly limited, and can be appropriately selected according to the state of the administration target. It may be administered prophylactically or used for maintenance therapy. Moreover, it is preferable that a dosage form is determined according to a formulation form, a patient's age, sex, other conditions, a patient's symptom, its grade, etc.
  • the drug of the present invention can be administered once or a plurality of times a day, or can be administered once every several days or weeks.
  • the drug of the present invention or the bacteria belonging to Bifidobacterium breve, which is an active ingredient thereof, and lactulose, raffinose, and galactooligosaccharide can also be contained in food and drink (beverage or food).
  • a food belonging to Bifidobacterium breve, and lactulose, raffinose, and galactooligosaccharide, or a drug of the present invention are contained in food and drink as active ingredients, and as one aspect of an immune development promoting agent, an immune development promoting action is provided. It is also possible to process it as a food or drink. That is, this invention provides the food-drinks composition for promoting immune development which uses the bacteria which belong to Bifidobacterium breve, and lactulose, raffinose, and galactooligosaccharide as an active ingredient.
  • the form and properties are not particularly limited as long as they can be taken orally without impairing the effects of promoting immune development, including bacteria belonging to Bifidobacterium breve, and lactulose, raffinose, and galactooligosaccharides Except making it, it can manufacture by a normal method using the raw material normally used for food-drinks.
  • the foods and drinks mentioned above are not limited to liquid, paste-like, gel-like solids, powders, etc.
  • bread, macaroni, spaghetti, noodles, cake mix, fried Flour products such as flour and bread crumbs; instant noodles, cup noodles, retort / cooked food, cooking canned food, microwave food, instant soup / stew, instant miso soup / soup, canned soup, freeze-dried food, other instant foods, etc.
  • Foods Canned agricultural products, canned fruits, jams, marmalades, pickles, boiled beans, dried agricultural products, processed cereals (cereal products), canned fish, fish hams and sausages, marine products, marine delicacies, Processed marine products such as tsukudani; Livestock canned and pasted products, processed livestock products such as meat ham and sausage; processed milk, milk drinks, yogurts Milk and dairy products such as lactic acid bacteria beverages, cheese, ice cream, formula milk powder, cream, other dairy products; fats and oils such as butter, margarines, vegetable oils; soy sauce, miso, sauces, tomato processed seasonings, Basic seasonings such as mirin, vinegar, etc .; cooking mixes, curry ingredients, sauces, dressings, noodle soups, spices, and other complex seasonings and foods; frozen foods, semi Frozen foods such as cooked frozen foods and cooked frozen foods; caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pie, snacks, crackers, Japanese confectionery, rice confectionery,
  • the food / beverage products of the present invention can be sold as food / beverage products displaying the use for promoting immune development.
  • such foods and drinks can be labeled as “for promoting immune development”.
  • the “display” means all acts for informing the consumer of the use, and if it is a display that can recall and analogize the use, the purpose of the display, the content of the display, the display Regardless of the object and medium to be processed, all fall under the “display” of the present invention. However, it is preferable to display in such an expression that the consumer can directly recognize the application.
  • the act of describing the above-mentioned use in the product or product packaging relating to the food or drink of the present invention the product or product packaging describing the above-mentioned use is transferred, and displayed for delivery, transfer or delivery And importing, displaying advertisements on products, price lists or transaction documents for display or distribution, or describing the above uses in information containing these, electromagnetic (Internet, etc.) methods
  • the display is preferably a display permitted by the government or the like (for example, a display that is approved based on various systems determined by the government and is performed in a mode based on such approval).
  • health food, functional food, enteral nutrition food, special purpose food, nutritional functional food, quasi-drugs, etc. can be exemplified, other indications approved by the Consumer Affairs Agency, for example, Examples of health functional foods, more specifically, foods for specified health use, nutritional functional foods, functional labeling foods, and labels approved by a similar system. Examples of the latter include labeling as food for specified health use, labeling as conditionally specified food for specified health use, labeling that affects the structure and function of the body, labeling for reducing disease risk, and functionality based on scientific evidence The display etc.
  • Bacteria belonging to Bifidobacterium breve, as well as lactulose, raffinose, and galactooligosaccharides can be included in the feed as active ingredients and processed as a feed having an immune development promoting action as one aspect of the immune development promoting agent. It is.
  • the form of the feed is not particularly limited, for example, grains such as corn, wheat, barley, rye, milo; vegetable oils such as soybean oil meal, rapeseed oil meal, coconut oil meal, linseed oil meal; bran, wheat straw, rice bran, Dehydrated rice bran, etc .; Manufactured deer such as corn gluten meal, corn jam meal; Animal feed such as fish meal, non-fat dry milk, whey, yellow grease, tallow; Yeasts such as torula yeast, beer yeast; It can be produced by blending mineral feed such as calcium phosphate and calcium carbonate; fats and oils; simple amino acids; sugars and the like. Examples of the form of the feed include pet food, livestock feed, and fish feed.
  • the amount of bacteria belonging to Bifidobacterium breve, and lactulose, raffinose, and galactooligosaccharides contained in the food and drink (including feed) of the present invention is not particularly limited and may be appropriately selected. This is the same as the drug of the present invention described above.
  • Example 1 Ratio of Foxp3 positive cells and RORgt positive cells among CD4 positive cells in mouse colonic lamina limba lymphocytes and mesenteric lymph node lymphocytes, and changes in the number of cells over time
  • C57BL / 6J male mice were purchased from Japan SLC with their mothers. Infant mice were fed freely with maternal milk. Infant mice are divided into two groups so that weight does not become biased, one group is 14 days old and the other group is 21 days old, and each of them is dissected, and the large intestine and mesenteric lymph nodes (mesenteric lymph nodes) node (hereinafter sometimes referred to as “MLN”).
  • MSN large intestine and mesenteric lymph nodes
  • the obtained large intestine sample was cut vertically and transferred to DPBS (Dulbecco PBS) containing 5 mM EDTA, 1 mM mM DTT, and 2% fetal calf serum (FCS), and shaken in a 37 ° C. thermostat for 30 minutes. Thereafter, the sample was passed through a 70 ⁇ m mesh to remove the liquid containing epithelial cells.
  • the remaining large intestine sample contains 0.5 mg / ml collagenase (Sigma), 25 ⁇ g / ml DNase® I (Roche Diagnostics), 50 ⁇ g / ml dispase (Gibco), 0.01 M HEPES, and 2% FCS Placed in RPMI 1640 medium and digested at 37 ° C for 30 minutes.
  • the digested solution was filtered through a 70 ⁇ m mesh, and the obtained filtrate was centrifuged at 340 ⁇ g and 4 ° C. for 5 minutes to obtain a cell suspension.
  • the obtained cell suspension and Percoll solution were mixed to obtain a 40% Percoll cell suspension, which was overlaid on the upper layer of the 90% Percoll solution.
  • MN lymphocytes Mesenteric lymph node lymphocytes (MLN lymphocytes; hereinafter sometimes referred to as “MLNL”) were ground on a 70 ⁇ m mesh to obtain a cell suspension that passed through the mesh.
  • the obtained LPL and MLNL were treated with FITC-labeled anti-mouse CD4 antibody (clone number: RM4-5, manufactured by BD Biosciences), APC (allophycocyanin) -labeled anti-rat / mouse Foxp3 (clone number: FJK-16a, e -Bioscience), PE (phycoerythrin) labeled anti-human / mouse RORgt (clone number: AFKJS-9, e-Bioscience), Foxp3pStaining Buffer set (e-Bioscience)
  • the cells were analyzed using a FACSCanto flow cytometer (BD Biosciences), and data analysis was performed using FlowJo software (TreeStar).
  • Tables 1 to 4 show the ratios (average value, unit:%) of Foxp3 positive cells and RORgt positive cells to CD4 positive cells.
  • Tables 1 to 4 show the ratios (average value, unit:%) of Foxp3 positive cells and RORgt positive cells to CD4 positive cells.
  • the percentage of Foxp3 positive cells (Treg cells) in CD4 positive cells increased with increasing age
  • MLNL the percentage of Foxp3 positive cells in CD4 positive cells changed with increasing age.
  • Example 2 Effect of Bifidobacterium breve and three oligosaccharides on the ratio of Foxp3 positive cells and RORgt positive cells in CD4 positive cells in mouse colon LPL and MLNL Bifidobacterium breve in starch M-16V cell powder (2.4 ⁇ 10 11 cfu / g, Morinaga Milk Industry Co., Ltd.) was suspended in physiological saline to prepare a 2.5 ⁇ 10 9 cfu / ml bifidobacteria solution.
  • Lactulose manufactured by Morinaga Milk Industry Co., Ltd.
  • raffinose product name: Nitten Raffinose, manufactured by Nippon Sesame Sugar Co., Ltd.
  • galactooligosaccharide is mixed and dissolved in distilled water at a weight ratio of 1: 1: 1, for a total final concentration of 250 mg / ml.
  • An oligosaccharide solution was prepared.
  • Galactooligosaccharide is a product obtained by removing monosaccharide and disaccharide from a commercial product (product name Oligomate 55N, manufactured by Yakult Pharmaceutical Co., Ltd.), Gal ⁇ 1-4Gal ⁇ 1-4Glc (4′-galactosyl lactose) is about 65% by weight, About 15% by weight of Gal ⁇ 1-6Gal ⁇ 1-4Glc (6′-galactosyl lactose) is contained.
  • mice 2 days old C57BL / 6J male mice were purchased from Japan SLC together with their mothers. Infant mice were fed freely with maternal milk. It was divided into the following three groups so that there was no bias in body weight at 5 days of age.
  • A Vehicle group (administer physiological saline)
  • each group of infant mice is given once a day with physiological saline, bifidobacterial solution dilution, or a mixture of bifidobacterial solution and oligosaccharide solution (1: 4). 100 ⁇ l was administered. That is, for each administration, 5 ⁇ 10 7 cfu Bifidobacterium breve M-16V is used for the Bifidobacterium group, 20 mg oligosaccharide and 5 ⁇ 10 7 cfu Bifidobacterium is used for the oligosaccharide + Bifidobacterium group. • Breve M-16V was administered.
  • M-16V means Bifidobacterium breve M-16V
  • M-16V + oligosaccharide means a mixture of Bifidobacterium breve M-16V and lactulose, raffinose and galactooligosaccharide.
  • Example 3 Effect of Bifidobacterium breve and three oligosaccharides on the number of CD4-positive Foxp3-positive cells and RORgt-positive cells in mouse MLNL
  • milk administered with each administration The pups were dissected at 14 days of age, and the numbers of Foxp3-positive cells and RORgt-positive cells among CD4-positive cells in MLNL were examined.
  • the results are shown in Tables 12 to 14 (average value, unit: ⁇ 10 6 ).
  • the total number of cells in MLNL, the number of CD4-positive Foxp3-positive cells, and the number of CD4-positive RORgt-positive cells increased by administration of Bifidobacterium breve M-16V and oligosaccharide.
  • the immune development promoter of the present invention is effective for promoting immune development in mammals. Immune development promoters are useful for the prevention and treatment of various diseases that are effective in promoting immune development.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Mycology (AREA)
  • General Health & Medical Sciences (AREA)
  • Food Science & Technology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Biotechnology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Physiology (AREA)
  • Animal Husbandry (AREA)
  • General Engineering & Computer Science (AREA)
  • Virology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Fodder In General (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

Selon l'invention, une bactérie appartenant aux bifidobacterium breve, par exemple, un bifidobacterium breve Ｍ－１６Ｖ（ＬＭＧ２３７２９）, un lactulose, une raffinose et un galacto-oligosaccharide, sont les principes actifs d'un agent favorisant le développement d'immunité.
PCT/JP2016/075071 2016-02-26 2016-08-26 Agent favorisant le développement d'immunité WO2017145415A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2018500972A JP6773368B2 (ja) 2016-02-26 2016-08-26 免疫発達促進剤
PH12018501822A PH12018501822A1 (en) 2016-02-26 2018-08-28 Immune development accelerator

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2016035957 2016-02-26
JP2016-035957 2016-02-26

Publications (1)

Publication Number Publication Date
WO2017145415A1 true WO2017145415A1 (fr) 2017-08-31

Family

ID=59686031

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2016/075071 WO2017145415A1 (fr) 2016-02-26 2016-08-26 Agent favorisant le développement d'immunité

Country Status (3)

Country Link
JP (1) JP6773368B2 (fr)
PH (1) PH12018501822A1 (fr)
WO (1) WO2017145415A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019002607A1 (fr) * 2017-06-30 2019-01-03 N.V. Nutricia Composition symbiotique pour la prévention de troubles
WO2019002612A1 (fr) * 2017-06-30 2019-01-03 N.V. Nutricia Composition symbiotique pour la prévention de troubles métaboliques
WO2019180965A1 (fr) * 2018-03-23 2019-09-26 森永乳業株式会社 Composition pour nourrisson destinée à prévenir les maladies provoquées par l'hyperglycémie à partir de l'âge scolaire
WO2019180964A1 (fr) * 2018-03-23 2019-09-26 森永乳業株式会社 Composition favorisant la sécrétion de fgf21

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10175867A (ja) * 1996-12-12 1998-06-30 Morinaga Milk Ind Co Ltd ビフィズス菌増殖促進組成物及びその用途

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5836236B2 (ja) * 2012-09-25 2015-12-24 特定非営利活動法人日本健康増進支援機構 乳幼児用アレルギー疾患予防剤

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10175867A (ja) * 1996-12-12 1998-06-30 Morinaga Milk Ind Co Ltd ビフィズス菌増殖促進組成物及びその用途

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
DE KIVIT, S ET AL.: "Galectin-9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans", ALLERGY, vol. 67, 2012, pages 343 - 352, XP055412942 *
SAGAR, SEIL ET AL.: "The combination of Bifidobacterium breve with non-digestible oligosaccharides suppresses airway inflammation in a murine model for chronic asthma", BIOCHIM. BIOPHYS. ACTA, vol. 1842, 2014, pages 573 - 583, XP028617179 *
TAIZO NAGURA ET AL.: "Prebiotics to Men'eki", THE JAPANESE JOURNAL OF CLINICAL NUTRITION, vol. 102, no. 5, 2003, pages 556 - 559, XP003020341 *
ZHENG, BIN ET AL.: "Bifidobacterium breve Attenuates Murine Dextran Sodium Sulfate- Induced Colitis and Increases Regulatory T Cell Responses", PLOS ONE, vol. 9, no. 5, 2014, pages e95441, XP055294968 *

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019002607A1 (fr) * 2017-06-30 2019-01-03 N.V. Nutricia Composition symbiotique pour la prévention de troubles
WO2019002612A1 (fr) * 2017-06-30 2019-01-03 N.V. Nutricia Composition symbiotique pour la prévention de troubles métaboliques
WO2019002609A1 (fr) * 2017-06-30 2019-01-03 N.V. Nutricia Composition symbiotique pour la prévention de troubles métaboliques
US11641868B2 (en) 2017-06-30 2023-05-09 N.V. Nutricia Synbiotic composition for preventing metabolic disorders
US11638438B2 (en) 2017-06-30 2023-05-02 N.V. Nutricia Synbiotic composition for preventing metabolic disorders
US11638729B2 (en) 2017-06-30 2023-05-02 N.V. Nutricia Synbiotic composition for preventing disorders
JPWO2019180964A1 (ja) * 2018-03-23 2020-12-03 森永乳業株式会社 Ｆｇｆ２１分泌促進用組成物
JPWO2019180965A1 (ja) * 2018-03-23 2021-02-04 森永乳業株式会社 学童期以降の高血糖に起因する疾患の予防のための乳幼児用組成物
JP7152472B2 (ja) 2018-03-23 2022-10-12 森永乳業株式会社 Ｆｇｆ２１分泌促進用組成物
JP7266580B2 (ja) 2018-03-23 2023-04-28 森永乳業株式会社 学童期以降の高血糖に起因する疾患の予防のための乳幼児用組成物
CN111954536A (zh) * 2018-03-23 2020-11-17 森永乳业株式会社 用于预防学龄期及之后的高血糖引起的疾病的婴幼儿用组合物
WO2019180964A1 (fr) * 2018-03-23 2019-09-26 森永乳業株式会社 Composition favorisant la sécrétion de fgf21
AU2018414925B2 (en) * 2018-03-23 2023-05-04 Morinaga Milk Industry Co., Ltd. Composition for promoting the secretion of FGF21
WO2019180965A1 (fr) * 2018-03-23 2019-09-26 森永乳業株式会社 Composition pour nourrisson destinée à prévenir les maladies provoquées par l'hyperglycémie à partir de l'âge scolaire
US11857579B2 (en) 2018-03-23 2024-01-02 Morinaga Milk Industry Co., Ltd. Composition for promoting the secretion of FGF21

Also Published As

Publication number Publication date
JPWO2017145415A1 (ja) 2018-12-20
PH12018501822A1 (en) 2019-05-15
JP6773368B2 (ja) 2020-10-21

Similar Documents

Publication Publication Date Title
US11566219B2 (en) Bifidobacterium bacteria and composition including novel bifidobacterium bacteria
EP3725321A1 (fr) Composition contenant une bactérie appartenant au genre bifidobacterium en tant que substance active
JP7303296B2 (ja) 栄養組成物
WO2017130859A1 (fr) Inhibiteur de l'apoptose des cellules neuronales
JP6773368B2 (ja) 免疫発達促進剤
JP7240327B2 (ja) 新規ビフィドバクテリウム属細菌及び当該細菌を含む組成物
JP6998193B2 (ja) 新規ビフィドバクテリウム属細菌及び当該細菌を含む組成物
JP2020164493A (ja) 筋肉炎症抑制用組成物及び腸管炎症抑制用組成物
JP7209085B2 (ja) 組成物
WO2021015107A1 (fr) Composition
US11730171B2 (en) Composition for enhancing breast milk component
CN111201026A (zh) 具有癌性恶病质抑制作用的发酵乳和多糖类
JP6705628B2 (ja) 形質細胞様樹状細胞誘導剤
JP7266580B2 (ja) 学童期以降の高血糖に起因する疾患の予防のための乳幼児用組成物
EP3892331A1 (fr) Composition servant à la suppression d'une infection au norovirus
WO2020251044A1 (fr) Composition ayant pour principe actif une bactérie bifidobacterium
JP6978621B1 (ja) 組成物
WO2007123236A1 (fr) Composition contenant une cellule de micro-organisme pouvant empêcher l'évolution de la maladie de hansen
WO2022255441A1 (fr) Composition
JP2023062563A (ja) 栄養組成物
JP2023055389A (ja) バクテロイデス属細菌の増殖促進剤
JP2022016960A (ja) 健康寿命延長用組成物

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 2018500972

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16891572

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 16891572

Country of ref document: EP

Kind code of ref document: A1