+

WO2018190407A1 - COMPOSITION PERMETTANT D'ACTIVER UN RÉCEPTEUR DE TYPE Toll 2 - Google Patents

COMPOSITION PERMETTANT D'ACTIVER UN RÉCEPTEUR DE TYPE Toll 2 Download PDF

Info

Publication number
WO2018190407A1
WO2018190407A1 PCT/JP2018/015465 JP2018015465W WO2018190407A1 WO 2018190407 A1 WO2018190407 A1 WO 2018190407A1 JP 2018015465 W JP2018015465 W JP 2018015465W WO 2018190407 A1 WO2018190407 A1 WO 2018190407A1
Authority
WO
WIPO (PCT)
Prior art keywords
barrier function
bifidobacterium bifidum
present
improving
intestinal barrier
Prior art date
Application number
PCT/JP2018/015465
Other languages
English (en)
Japanese (ja)
Inventor
慎治 神野
中村　吉孝
香枝 山▲崎▼
Original Assignee
株式会社明治
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 株式会社明治 filed Critical 株式会社明治
Publication of WO2018190407A1 publication Critical patent/WO2018190407A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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 a composition for activating Toll-like receptor 2.
  • innate immunity In contrast to acquired immunity that exists only in higher organisms such as humans, innate immunity is an immune mechanism that is widely conserved from insects to humans. When cells in charge of innate immunity (macrophages, dendritic cells, etc.) enter the pathogenic bacteria from the outside world, they quickly detect them and emit warning signals such as cytokines in addition to direct attacks such as phagocytosis. It functions as the first step of infection protection by activating the acquired immune system.
  • a receptor protein that plays a role in discovering bacteria as the first trigger in such a series of immune reaction systems is a Toll-like receptor (referred to herein as “TLR”).
  • TLR2 is known to mediate cell signaling in response to microbial cell wall components such as peptidoglycan (PGN), lipoteichoic acid, microbial lipoproteins, and zymosan (Non-Patent Document 1).
  • PPN peptidoglycan
  • Non-Patent Document 1 peptidoglycan
  • the activation of TLR2 can improve the intestinal barrier function through enhanced protection of tight junctions in the intestinal tract.
  • cell signaling via TLR2 governs various in vivo reactions including the biological immune system.
  • the present inventors paid attention to the usefulness of the cell signal transmission system via TLR2, and conducted intensive studies on food materials capable of activating TLR2. As a result, it was found that bacteria belonging to Bifidobacterium bifidum (particularly Bifidobacterium bifidum OLB6378) have a strong TLR2 activation ability.
  • an object of the present invention is to provide a novel Toll-like receptor 2 activation composition and Toll-like receptor 2 activator.
  • a composition for activating TLR2 and a TLR2 activator comprising a bacterium belonging to Bifidobacterium bifidum (hereinafter sometimes referred to as “bifidobacteria of the present invention”) or a processed product thereof as an active ingredient (Hereafter, it may be called “the composition and agent of this invention.”).
  • bifidobacteria of the present invention a bacterium belonging to Bifidobacterium bifidum
  • the composition and agent of this invention comprising a bacterium belonging to Bifidobacterium bifidum (hereinafter sometimes referred to as “bifidobacteria of the present invention”) or a processed product thereof as an active ingredient (Hereafter, it may be called “the composition and agent of this invention.”).
  • composition according to [5] above, wherein the disease is necrotizing enterocolitis, ulcerative colitis, persistent diarrhea, allergic disease or food hypersensitivity.
  • a method for activating TLR2 and improving intestinal barrier function comprising ingesting or administering an effective amount of a bacterium belonging to Bifidobacterium bifidum or a processed product thereof to a subject in need thereof Methods and methods for treating, preventing and / or ameliorating diseases or symptoms that can be treated, prevented or ameliorated by improving intestinal barrier function.
  • a therapeutic agent preventive agent or ameliorating agent for a disease or condition that can be treated, prevented or ameliorated by improving the intestinal barrier function, or treating, preventing or ameliorating by improving the intestinal barrier function
  • a bacterium belonging to Bifidobacterium bifidum or a processed product thereof for the treatment, prevention and / or amelioration of a possible disease or symptom.
  • compositions and preparations of the present invention activation of TLR2 and its related effects can be expected in ingestion subjects and administration subjects.
  • Bacteria belonging to Bifidobacterium bifidum, which is an active ingredient of the present invention, are bacteria contained in food materials that have been ingested by civilization for many years. Therefore, the compositions and preparations of the present invention have no side effects. This is advantageous in that activation of TLR2 can be achieved.
  • the active ingredient of the present invention is a bacterium belonging to Bifidobacterium bifidum .
  • the bacterium belonging to Bifidobacterium bifidum has a strong TLR2 activation ability. That is, in the present invention, the Bifidobacterium having Toll-like receptor 2 activation ability higher than the Toll-like receptor 2 activation ability of the general-purpose strain Bifidobacterium breve JCM1192T strain.
  • Bacteria belonging to bifidum can be used as an active ingredient, preferably 2 times or more (preferably 2.2 times or more, more preferably 2.4 times or more) with respect to Bifidobacterium breve JCM1192T strain
  • Bacteria belonging to Bifidobacterium bifidum having Toll-like receptor 2 activation ability can be used as active ingredients.
  • Bifidobacterium breve JCM1192T strain can be obtained from RIKEN, BioResource Center, Microbial Materials Development Office.
  • the degree of TLR2 activation ability can be evaluated using the concentration of alkaline phosphatase (SEAP) secreted by TLR2 activation as an index.
  • SEAP alkaline phosphatase
  • Bifidobacterium bifidum OLB6378 strain Bactetrachlorobacterium bifidum OLB6378, Accession Number: NITE BP-31
  • This strain is deposited with the Patent Microorganism Depositary Center for Product Evaluation Technology. The contents specifying the deposit are described below.
  • Bifidobacterium bifidum OLB6378 is a Gram-positive obligate anaerobe derived from human infant feces.
  • this bacterium is applied on a plate of BL agar medium (Eiken Chemical Co., Ltd.) and cultured at 37 ° C for 48 hours in anaerobic condition using AnaeroPack Kenki (Mitsubishi Gas Chemical Co., Ltd.), an opaque circular hemispherical gloss is obtained. A colony is formed.
  • amplification products are observed by PCR using specific primers of Bifidobacterium bifidum (Intestinal Flora Symposium 8, Molecular Biology Detection and Identification of Intestinal Flora, Toshihiro Mitsuoka, Takahiro Matsumoto). Moreover, it has fermentability with respect to galactose, glucose, fructose, lactose, and gentiobiose.
  • a medium usually used for a bifidobacteria medium can be used. That is, the medium that can be used in the present invention is not particularly limited, and any medium can be used as long as it contains a nitrogen source, an inorganic substance, and other nutrients in a predetermined range in addition to the main carbon source.
  • the carbon source lactose, glucose, sucrose, fructose, starch hydrolysate, molasses, etc. can be used according to the assimilation ability of the bacteria used.
  • organic nitrogen-containing substances such as casein hydrolyzate, whey protein hydrolyzate, and soy protein hydrolyzate can be used.
  • meat extract, fish extract, yeast extract, etc. can be used as a growth promoter.
  • the bifidobacteria of the present invention is preferably cultured under anaerobic conditions, and a known method such as a method of culturing while aeration of carbon gas can be applied. Culture can also be performed using other techniques such as air conditions or batch culture conditions.
  • the culture temperature is preferably 25 to 50 ° C., and particularly preferably 35 to 42 ° C. However, the present invention is not limited to this, and other temperature conditions may be used as long as the bacteria can grow.
  • the pH of the medium during the culture is preferably maintained at 6.0 to 7.0, but may be other pH conditions as long as the bacteria can grow.
  • the culture time is preferably 3 to 48 hours, more preferably 8 to 24 hours, and particularly preferably 10 to 20 hours. However, other culture time may be used as long as the bacteria can grow.
  • the obtained microbial cells can be contained in the composition and the preparation of the present invention as a processed product subjected to the following treatment.
  • the processed product of bifidobacteria of the present invention includes a culture that is still after completion of the culture, a culture that has been subjected to centrifugation or filtration after the completion of the culture, a concentrate thereof, and further processed into a paste, various methods Dried products (spray-dried products, freeze-dried products, vacuum-dried products, drum-dried products, etc.), liquids dispersed in media, diluents with diluents, heat-treated foods (heat-treated cells), ultraviolet rays And / or radiation-treated products (light-treated cells) treated with radiation, drug-treated products (drug-treated cells) treated with chemicals (bactericides, antibacterial agents, bacteriostatic agents), dried products with a mill, etc.
  • crushed crushed material is included. Centrifugation, filtration, and concentration are performed by commonly used techniques. Drying can be performed by, for example, vacuum drying, spray drying, freeze drying, drum drying, or the like. In the present specification, these may be simply abbreviated as “processed products”.
  • Bacteria belonging to Bifidobacterium bifidum obtained by the above method and processed products thereof are live bacteria, or heat-treated bacteria, and then processed as a crushed or unground product, or a mixture of plural kinds Can be contained in the composition and the preparation of the present invention. If it is a living bacterium, effects such as growth and colonization in the intestine after ingestion or administration can be expected, and further, the effects of the present invention can be expected to be sustained.
  • 0.1 mL of a heat-treated cell for example, a suspension (dispersion) of the heat-treated cell
  • a heat-treated cell for example, a suspension (dispersion) of the heat-treated cell
  • the colony is not formed even if cultured, it is not necessary to consider the characteristics of bifidobacteria that it is difficult to survive in the presence of oxygen, and the composition and agent of the present invention This is preferable because the application range is expanded.
  • the heating temperature is usually 60 to 300 ° C., preferably 60 to 200 ° C., more preferably 60 to 150. ° C, more preferably 60-140 ° C, more preferably 60-130 ° C, more preferably 60-120 ° C, more preferably 60-110 ° C, more preferably 60-100 ° C, more preferably 70-100 ° C, More preferably, it is 80 to 100 ° C, particularly preferably 85 to 95 ° C. It is preferable to set the heat treatment condition at 60 ° C. or higher because vegetative cells of the fungus are sterilized. Further, it is preferable that the temperature of the heat treatment is 300 ° C. or lower because the bacteria remain without being carbonized.
  • the heat treatment time is, for example, 0.01 to 120 minutes, preferably 0.015 to 60 minutes, more preferably 0.02 to 40 minutes, still more preferably 0.025 to 30 minutes, and still more preferably 0. 0.03 to 25 minutes, particularly preferably 0.03 to 20 minutes. It is preferable to set the heat treatment time to 0.1 minutes or longer, because the vegetative cells of Bifidobacterium are sterilized. In addition, it is preferable that the heat treatment time is 120 minutes or less because heat denaturation can be suppressed and vegetative cells can be sterilized efficiently.
  • the optimum heat treatment time is, for example, 0.2 to 120 minutes, preferably 0.2 to 60 minutes, more preferably 0.2 to 40 minutes in the heat treatment at a low temperature range (60 to 100 ° C.). More preferably, it can be 0.2 to 30 minutes, more preferably 0.2 to 25 minutes, and particularly preferably 0.2 to 20 minutes.
  • a high temperature range 100 to 300 ° C.
  • 0.01 to 0.5 minutes preferably 0.015 to 0.5 minutes, more preferably It is 0.02 to 0.5 minutes, more preferably 0.025 to 0.5 minutes, further preferably 0.03 to 0.5 minutes, and particularly preferably 0.03 to 0.5 minutes.
  • the heat treatment is performed at 90 ° C. for 15 minutes.
  • the heat treatment method is not particularly limited.
  • the obtained microbial cells can be heated under predetermined conditions using a heat sterilizer such as a plate sterilizer, a tubular sterilizer, a direct heating sterilizer, a jacketed tank, or the like.
  • composition and agent of the present invention can be provided by the bifidobacteria of the present invention or a processed product thereof alone, or can be provided by mixing the bifidobacteria of the present invention or the processed product thereof with other components. You can also.
  • the compounding amount of the bifidobacteria of the present invention in the composition and the agent of the present invention can be arbitrarily determined according to the purpose, application, form, dosage form, symptom, body weight, etc., and the present invention is not limited thereto. However, the content can be blended at a content of 0.1 to 90% (w / w) relative to the total amount, more preferably at a content of 0.1 to 50% (w / w). Can be blended.
  • the agent of the present invention comprises the bifidobacteria of the present invention or a processed product thereof
  • the composition of the present invention comprises the bifidobacteria of the present invention or a processed product thereof and other components. It can be.
  • the bifidobacteria and its processed product of the present invention can activate TLR2.
  • activation of TLR2 can improve intestinal barrier function through protection of intestinal tight junction (see Non-Patent Document 2). Therefore, the composition and agent of the present invention can improve the intestinal barrier function through TLR2 activation. That is, according to the present invention, an intestinal barrier function improving composition and an intestinal barrier function improving agent comprising the bifidobacteria of the present invention or a processed product thereof as an active ingredient are provided.
  • intestinal barrier function refers to a function of protecting the intestine from food antigens, bacteria and viruses that enter the intestine together with food, intestinal bacteria, and harmful substances produced by these.
  • intestinal barrier function improvement is used in the meaning including “recovery of intestinal barrier function” and “inhibition of enhancement of intestinal barrier permeability”.
  • Improving intestinal barrier function is further used in the meaning including enhancing the lowered intestinal barrier function, suppressing the decrease in barrier function, and further enhancing the barrier function of the normal intestinal tract.
  • recovery of the intestinal barrier function means recovery from a state in which the permeability in the intestinal tract has increased beyond a normal range to a pathological or undesirable level for some reason, It is used not only to return to, but also to bring it close to a qualitatively normal state.
  • promotion of recovery that shortens the recovery period until recovery from a state where the permeability in the intestinal tract exceeds a normal range for some reason and is pathologically or undesirably increased, in other words, usually Compared to the case of taking the food, it is used in a sense including restoring to a normal state earlier than natural healing.
  • “inhibition of increased permeability of the intestinal barrier” means that the barrier function in the intestinal tract is destroyed due to an exogenous or intrinsic cause, and the permeability of the intestinal barrier is changed from a normal state to a pathological state. It is used in the meaning of preventing or suppressing the occurrence of the phenomenon and maintaining its permeability in a normal state.
  • the enhancement of intestinal barrier permeability as used in the present invention includes not only epithelial cells, but also destruction, breakdown, weakness, and reduction of the intestinal barrier related to biological mechanisms that constitute other intestinal barriers such as intestinal mucosa. .
  • the bifidobacteria of the present invention and the processed product thereof have actions such as improvement of diarrhea, improvement of constipation, suppression of growth of harmful bacteria in the intestine, production of vitamin B group, promotion of digestion and absorption by decomposition of lactose, etc. It has been known. Therefore, in addition to the activation of TLR2 and the effects related thereto, the effects and effects of the composition and agent of the present invention can be expected.
  • the bifidobacteria of the present invention and the processed product thereof can activate TLR2, and thus improve the intestinal barrier function.
  • necrotic enteritis, ulcerative colitis, persistent diarrhea, allergic disease and food hypersensitivity, etc. develop due to the breakdown or decrease of intestinal barrier function (Guamer F et al., Eur J Clin Nutr, 56 (Suppl 4), S34-38 (2002) etc.). Therefore, the composition and the agent of the present invention can be used for treatment, prevention and / or improvement of a disease or symptom which can be treated, prevented or ameliorated by improving intestinal barrier function.
  • treatment, prevention and / or improvement of a disease or symptom which can be treated, prevented or ameliorated by improving the intestinal barrier function comprising the bifidobacteria of the present invention or a processed product thereof as an active ingredient.
  • a therapeutic, preventive and / or ameliorating agent for the disease or condition include necrotizing enterocolitis, ulcerative colitis, persistent diarrhea, allergic diseases and food sensitivity.
  • composition and agent of the present invention and the therapeutic agent, preventive agent and improver of the present invention can be provided in the form of a pharmaceutical (eg, pharmaceutical composition), quasi-drug, food, feed, etc. Can be performed as described.
  • the bifidobacteria and processed products thereof of the present invention can be orally administered to humans and non-human animals.
  • Oral preparations include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, and suspensions. These preparations can be formulated using a pharmaceutically acceptable carrier by a technique usually performed in this field.
  • Pharmaceutically acceptable carriers include excipients, binders, diluents, additives, fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, etc. Is mentioned.
  • the oral preparation may be provided as an enteric preparation so that it does not dissolve in the stomach but dissolves in the intestine.
  • it can be provided as a capsule, or the surface of a tablet or the like can be coated with an enteric film. .
  • the bifidobacteria of the present invention and the processed product thereof can be administered to humans and non-human animals in the body other than oral administration such as tube administration, nasal tube administration, infusion, suppository, etc. Is possible depending on.
  • a viscous liquid composition containing the bifidobacteria of the present invention or a processed product thereof, or a semi-solid composition containing the bifidobacteria of the present invention or a processed product thereof can be used for chewing and swallowing functions.
  • the bifidobacteria and processed products thereof of the present invention can be taken orally by humans and non-human animals.
  • the food or raw material of the food containing the bifidobacteria of the present invention or the processed product thereof even in an isolated, purified or crudely purified form It may be a form.
  • the bifidobacteria of the present invention and the processed product thereof can be directly contained in the food, and the food contains the bifidobacteria of the present invention or the processed product thereof. It is a food containing an effective amount.
  • “containing an effective amount” of the bifidobacteria of the present invention and the processed product thereof means that the bifidobacteria of the present invention and the treatment thereof are within the range described later when an amount normally consumed in each food is ingested. Content that can be consumed.
  • Food means health food, functional food, health functional food (for example, food for specified health use, functional nutrition food, functional indication food), food for special use (for example, food for infants, food for pregnant women, disease, etc.) Food).
  • the form of “food” is not particularly limited.
  • it may be a liquid form such as a beverage or a liquid food, a paste form, a semi-liquid form, a gel form, a solid form or a powder form.
  • Form may be sufficient.
  • the bifidobacteria of the present invention and processed products thereof are various foods (milk, soft drinks, fermented milk, yogurt, cheese, bread, biscuits, crackers, pizza crust, preparation Powdered milk, liquid food, special-purpose food, food for the sick, nutritional food, frozen food, processed food, and other commercially available foods).
  • the usage form of a nutrient composition is a powder, it can manufacture by using means, such as spray drying and freeze-drying.
  • the bifidobacteria of the present invention or a processed product thereof may also be provided as a composition in which water, protein, carbohydrate, lipid, vitamins, minerals, organic acid, organic base, fruit juice, flavors and the like are mixed.
  • the protein include whole milk powder, skim milk powder, partially skim milk powder, casein, whey powder, whey protein, whey protein concentrate (WPC), whey protein isolate (WPI), ⁇ -casein, ⁇ -casein, ⁇ -Casein, ⁇ -lactoglobulin, ⁇ -lactalbumin, lactoferrin, soy protein, chicken egg protein, meat protein and other animal and vegetable proteins, hydrolysates thereof; butter, milk minerals, cream, whey, non-protein nitrogen, sial Examples include various milk-derived components such as acids, phospholipids, and lactose.
  • saccharide examples include saccharides, processed starch (in addition to dextrin, soluble starch, British starch, oxidized starch, starch ester, starch ether, etc.) and dietary fiber.
  • lipid examples include animal oils such as lard, fish oil, etc., fractionated oils, hydrogenated oil, transesterified oil, etc .; palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated oils thereof, Examples include vegetable oils such as hydrogenated oils and transesterified oils.
  • vitamins include vitamin A, carotene, vitamin B group, vitamin C, vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline.
  • folic acid examples include calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, and selenium.
  • examples of the organic acid include malic acid, citric acid, lactic acid, and tartaric acid. Any non-side effects that have been used as pharmaceuticals and foods are applicable. Moreover, these components can be used in combination of 2 or more types.
  • the daily intake or dose of the composition and the preparation of the present invention as a pharmaceutical or food is determined according to the pathological condition, age, symptom, body weight and use of the person to be ingested, and the composition and the preparation of the present invention are nutritious. Since it differs depending on whether it is the only thing, it is not particularly limited.
  • the intake or dose of the bifidobacteria of the present invention and its processed product per day is 10 8 per day, for example.
  • the number can be 10 ⁇ 10 9 to 3 ⁇ 10 10 , preferably 8 ⁇ 10 9 to 2 ⁇ 10 10 , and more preferably 9 ⁇ 10 9 to 2 ⁇ 10 10 .
  • the intake amount and dose may be determined by the ingestion subject and the attending physician of the administration subject.
  • composition and the preparation of the present invention are advantageous in that they can be provided as a composition and preparation for an age group that does not have sufficient physical strength because there is little risk of side effects.
  • the composition and agent of the present invention can be provided, for example, as a composition and agent for newborns (especially, newborn infants after birth), infants, children and / or elderly people.
  • newborns especially, newborn infants after birth
  • infants children and / or elderly people.
  • newborn refers to an infant that is shortly after birth, and is used to include healthy newborns, premature infants, premature infants, and low birth weight infants.
  • newborn refers to a child in the neonatal period
  • the term “newborn period” means a period just after birth. In the case of humans, the neonatal period usually falls within 4 weeks after birth.
  • composition and agent of the present invention can be provided as a composition and agent for daily intake that is effective in activating TLR2 and exerting its related effects.
  • the composition and the preparation of the present invention may be packaged so that the effective intake for one day of the bifidobacteria and the processed product of the present invention can be ingested.
  • the packaging form may be one package or a plurality of packages.
  • a description of the intake is provided on the package so that an effective intake for one day can be ingested, or a document with the description is provided together.
  • a plurality of packages with the effective intake for one day can be provided as a set for convenience of intake.
  • the packaging form for providing the composition and the agent of the present invention is not particularly limited as long as it is a form that defines a certain amount.
  • wrapping paper, bag, soft bag, paper container, can, bottle, capsule, etc. can be used.
  • composition and preparation of the present invention are preferably administered or ingested continuously for 1 week or more in order to exert their effects better, and the administration and ingestion period is more preferably 2 to 8 weeks, particularly preferably 2 ⁇ 4 weeks.
  • “continuously” means to continue administration or ingestion every day.
  • an effective intake for a certain period for example, one week
  • the present invention comprises ingesting or administering to a subject in need thereof an effective amount of a bacterium belonging to Bifidobacterium bifidum or a processed product thereof or a composition containing the same.
  • a TLR2 activation method a method for improving intestinal barrier function, and a method for treating, preventing and / or improving a disease or symptom that can be treated, prevented or ameliorated by improving the intestinal barrier function.
  • the subject of ingestion or administration is a mammal including a human, preferably a human.
  • the method of the present invention can be carried out as described for the compositions and agents of the present invention.
  • the present invention further provides use of a bacterium belonging to Bifidobacterium bifidum or a treated product thereof or a composition containing the same for the production of a TLR2 activator.
  • a bacterium belonging to Bifidobacterium bifidum or a treated product thereof or a composition containing the same for TLR2 activation there is provided use of a bacterium belonging to Bifidobacterium bifidum or a treated product thereof or a composition containing the same for TLR2 activation.
  • the microbe which belongs to Bifidobacterium bifidum, its processed material, or a composition containing it for using for TLR2 activation is provided.
  • the use of the present invention and the bifidobacteria of the present invention and the treated product thereof and the composition containing them can be carried out according to the description relating to the composition and the preparation of the present invention.
  • use of the treated product or a composition containing the same is provided.
  • the microbe which belongs to Bifidobacterium bifidum, its processed material, or the composition containing it for using for intestinal barrier function improvement is provided.
  • the use of the present invention and the bifidobacteria of the present invention and the treated product thereof and the composition containing them can be carried out according to the description relating to the composition and the preparation of the present invention.
  • the intestinal barrier function for the manufacture of a pharmaceutical composition for use in the treatment, prevention and / or improvement of a disease or condition that can be treated, prevented or ameliorated by improving the intestinal barrier function.
  • Treatment or prevention of a disease or condition that can be treated, prevented or ameliorated for the manufacture of a therapeutic agent, preventive agent or ameliorating agent for a disease or condition that can be treated, prevented or ameliorated, or by improving intestinal barrier function The use of a bacterium belonging to Bifidobacterium bifidum or a processed product thereof or a composition containing the same is provided for improvement.
  • a bacterium belonging to Bifidobacterium bifidum or a bacterium for use in the treatment, prevention and / or amelioration of a disease or symptom which can be treated, prevented or ameliorated by improving intestinal barrier function A treated product or a composition comprising the same is provided.
  • the use of the present invention and the bifidobacteria of the present invention and the treated product thereof and the composition containing them can be carried out according to the description relating to the composition and the preparation of the present invention.
  • non-therapeutic means not including an act of treating, treating or diagnosing a human (ie, a medical act on a human). Specifically, a doctor or a person who has received instructions from a doctor This means that it does not include methods for performing surgery, treatment or diagnosis on humans.
  • Example 1 Evaluation of TLR2 activation ability of Bifidobacterium bifidum OLB6378 Strain Bifidobacterium bifidum OLB6378 (Accession number: NITE BP-31) (Reference strain), Bifidobacterium infantis strain, and Bifidobacterium longum strain.
  • Each test strain specimen for evaluating the TLR2 activation ability was prepared as follows. That is, each test strain was cultured for 18 hours at 37 ° C. under anaerobic conditions using GAM Broth “Nissui” (manufactured by Nissui Pharmaceutical, product code 05422). The bacterial culture (500 mL) was centrifuged (2,000 ⁇ G, 15 minutes, 4 ° C.), and the resulting precipitate was resuspended in physiological saline (washing step). This washing step was repeated three times, twice with physiological saline and once with distilled water, and distilled water was added to the resulting precipitate to give a 20 mL bacterial suspension. This bacterial suspension was heated at 80 ° C. for 30 minutes and then freeze-dried to obtain a dry bacterial powder. The dried bacterial powder was suspended in distilled water at a concentration of 2 ⁇ g / mL and used for evaluation of TLR2 activation ability.
  • TLR2 Reporter Cell Line (manufactured by Novusbio, model number NBP2-26274), which is HEK293 cells into which each gene of TLR2 / NF ⁇ B / SEAP was introduced, was used. That is, TLR2 Reporter Cell Line was seeded in a 48-well plate at a concentration of 1.5 ⁇ 10 5 cells / mL in a volume of 250 ⁇ L, and cultured in a high glucose DMEM (10% FCS added) medium containing 4 mM glutamine for 24 hours. Thereafter, 250 ⁇ L each of the suspension (2 ⁇ g / mL) of each test strain prepared as described above was added (final concentration 1 ⁇ g / mL).
  • the culture supernatant 24 hours after the addition of the test strain was collected, and the concentration of alkaline phosphatase (SEAP) secreted by TLR2 Reporter Cell Line was quantified. Quantification was performed using SEAPorter Assay Kit (Novusbio, model number 10055K). The SEAP concentration at this time was used as an index of the TLR2 activation ability of each test strain.
  • SEAP alkaline phosphatase
  • the measurement result of TLR2 activation ability was as shown in FIG.
  • the Bifidobacterium bifidum OLB6378 strain had a significantly higher TLR2 activation ability than other test strains, and was about 2.4 times higher than the Bifidobacterium breve JCM1192T strain (reference strain).

Landscapes

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

Abstract

L'objet de la présente invention est de fournir une nouvelle composition permettant d'activer un récepteur de type Toll 2. La présente invention concerne une composition permettant d'activer un récepteur de type Toll 2 (TLR2) qui comprend des bactéries appartenant à Bifidobacterium bifidum ou un produit traité associé utilisé comme principe actif.
PCT/JP2018/015465 2017-04-14 2018-04-13 COMPOSITION PERMETTANT D'ACTIVER UN RÉCEPTEUR DE TYPE Toll 2 WO2018190407A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2017080361A JP2018177703A (ja) 2017-04-14 2017-04-14 Ｔｏｌｌ様受容体２活性化用組成物
JP2017-080361 2017-04-14

Publications (1)

Publication Number Publication Date
WO2018190407A1 true WO2018190407A1 (fr) 2018-10-18

Family

ID=63792540

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2018/015465 WO2018190407A1 (fr) 2017-04-14 2018-04-13 COMPOSITION PERMETTANT D'ACTIVER UN RÉCEPTEUR DE TYPE Toll 2

Country Status (3)

Country Link
JP (1) JP2018177703A (fr)
TW (1) TW201902499A (fr)
WO (1) WO2018190407A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10639319B2 (en) 2011-08-29 2020-05-05 Abbott Laboratories Human milk oligosaccharides for preventing injury and/or promoting healing of the gastrointestinal tract
US11179406B2 (en) 2010-12-31 2021-11-23 Abbott Laboratories Methods for decreasing the incidence of necrotizing enterocolitis in infants, toddlers, or children using human milk oligosaccharides
US11311562B2 (en) 2010-12-31 2022-04-26 Abbott Laboratories Methods for reducing the incidence of oxidative stress using human milk oligosaccharides, vitamin c and anti-inflammatory agents
US11446316B2 (en) 2011-07-22 2022-09-20 Abbott Laboratories Galactooligosaccharides for preventing injury and/or promoting healing of the gastrointestinal tract

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006087913A1 (fr) * 2005-02-02 2006-08-24 Meiji Dairies Corporation Composition pour l'activation immunitaire
JP2014505065A (ja) * 2011-01-31 2014-02-27 ナチュールヴォール ファーマ ゲーエムベーハー 消化器疾患への適用のためのビフィドバクテリウム・ビフィドゥムの菌株

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006087913A1 (fr) * 2005-02-02 2006-08-24 Meiji Dairies Corporation Composition pour l'activation immunitaire
JP2014505065A (ja) * 2011-01-31 2014-02-27 ナチュールヴォール ファーマ ゲーエムベーハー 消化器疾患への適用のためのビフィドバクテリウム・ビフィドゥムの菌株

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KHAILOVA, L. ET AL.: "Bifidobacterium bifidum reduces apoptosis in the intestinal epithelium in necrotizing enterocolitis", AM J PHYSIOL GASTROINTEST LIVER PHYSIOL, vol. 299, November 2010 (2010-11-01), pages G1118 - G1127, XP055559281, ISSN: 0193-1857, Retrieved from the Internet <URL:doi:10.1152/ajpgi.00131.2010> *
NAKAMURA, YOSHITAKA ET AL.: "Bifidobacterium bifidum OLB6378 as a potential for enhanced IgA secretion: its selection and mechanism", CELL, vol. 47, no. 2, 20 February 2015 (2015-02-20), pages 49 - 53, XP009510112, ISSN: 1346-7557 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11179406B2 (en) 2010-12-31 2021-11-23 Abbott Laboratories Methods for decreasing the incidence of necrotizing enterocolitis in infants, toddlers, or children using human milk oligosaccharides
US11311562B2 (en) 2010-12-31 2022-04-26 Abbott Laboratories Methods for reducing the incidence of oxidative stress using human milk oligosaccharides, vitamin c and anti-inflammatory agents
US11690859B2 (en) 2010-12-31 2023-07-04 Abbott Laboratories Methods for decreasing the incidence of necrotizing enterocolitis in infants, toddlers, or children using human milk oligosaccharides
US11446316B2 (en) 2011-07-22 2022-09-20 Abbott Laboratories Galactooligosaccharides for preventing injury and/or promoting healing of the gastrointestinal tract
US10639319B2 (en) 2011-08-29 2020-05-05 Abbott Laboratories Human milk oligosaccharides for preventing injury and/or promoting healing of the gastrointestinal tract

Also Published As

Publication number Publication date
TW201902499A (zh) 2019-01-16
JP2018177703A (ja) 2018-11-15

Similar Documents

Publication Publication Date Title
JP5273695B2 (ja) ビフィズス菌を有効成分とするアレルギー予防および／または治療剤
TWI359668B (fr)
JP7088829B2 (ja) 新生児向けの脳機能改善用組成物
WO2018190407A1 (fr) COMPOSITION PERMETTANT D&#39;ACTIVER UN RÉCEPTEUR DE TYPE Toll 2
US20190240268A1 (en) Infection protective agent for infants
Lokhande et al. A systematic study of probiotics-an update review
US20190201459A1 (en) Anti-allergic agent for infants
EP1997880A1 (fr) Bifidobactérie du lait maternel, composition correspondante, leur utilisation et milieu de culture pour les obtenir
WO2015087919A1 (fr) Agent inducteur de peptide antibactérien
TWI745454B (zh) 抑制腸道內乳桿菌屬乳酸菌減少用之組成物
WO2018003898A1 (fr) Composition facilitant la régénération du cartilage
CN115137074A (zh) 婴幼儿用排便促进剂
JP7531261B2 (ja) インターロイキン－２３産生促進用組成物

Legal Events

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

Ref document number: 18784148

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18784148

Country of ref document: EP

Kind code of ref document: A1

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载