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WO2018151245A1 - Composition et procédé favorisant la production d'interleukine-23 - Google Patents

Composition et procédé favorisant la production d'interleukine-23 Download PDF

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Publication number
WO2018151245A1
WO2018151245A1 PCT/JP2018/005414 JP2018005414W WO2018151245A1 WO 2018151245 A1 WO2018151245 A1 WO 2018151245A1 JP 2018005414 W JP2018005414 W JP 2018005414W WO 2018151245 A1 WO2018151245 A1 WO 2018151245A1
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Prior art keywords
interleukin
cells
production
lactobacillus
promoting
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PCT/JP2018/005414
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English (en)
Japanese (ja)
Inventor
杏輔 小林
幸夫 浅見
Original Assignee
株式会社 明治
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Application filed by 株式会社 明治 filed Critical 株式会社 明治
Priority to JP2018568622A priority Critical patent/JP7531261B2/ja
Publication of WO2018151245A1 publication Critical patent/WO2018151245A1/fr
Priority to JP2024100172A priority patent/JP2024111238A/ja

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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 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
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial 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 promoting production of interleukin-23, a method for promoting production of interleukin-23, and the like.
  • IL interleukin-23 secretion (production) promoter comprising a low molecular weight monocarboxylic acid such as acetic acid, lactic acid or thioglycolic acid
  • low molecular weight monocarboxylic acids such as acetic acid, lactic acid or thioglycolic acid have a relatively strong acidity and are difficult to take as they are. For this reason, in order to ingest a low molecular weight monocarboxylic acid without a sense of incongruity, processing such as formulation is required. Specifically, a troublesome work such as adding a sweetener or the like to change the taste or encapsulating is required.
  • An object of the present invention is to provide an IL-23 production promoter, a composition for promoting IL-23 production, and the like that can save troublesome work such as changing taste and encapsulating.
  • the composition for promoting IL-23 production according to the first aspect of the present invention contains bacterial cells as an active ingredient. That is, the bacterial cells are used as a composition for promoting IL-23 production or as a component thereof.
  • a microbial cell may be a living microbial cell or a dead microbial cell. When the cells are dead cells, the dead cells are preferably heat-killed cells, that is, cells killed by heat.
  • the “composition” referred to herein includes animals such as pharmaceuticals, supplements and food additives, foods and drinks (excluding animals and plants themselves), and food and drink compositions (including processed foods and drinks). Included are those that can be ingested (including humans).
  • the bacterial cells according to the first aspect of the present invention can promote the production of IL-23. That is, this microbial cell can favorably promote the production of IL-23.
  • IL-23 acts on ILC3 to induce the production of IL-22.
  • IL-22 is recognized by small intestinal epithelial cells, expression of antibacterial peptides such as Reg3 family proteins is induced. And, microorganisms such as foreign bacteria are killed by this antibacterial peptide, and expansion of microbial infection and excessive inflammatory reaction can be suppressed.
  • This effect is only an example, and it can be sufficiently assumed that IL-23 induces the production of other substances and other effects are manifested.
  • this microbial cell is tasteless. Therefore, when preparing the composition for promoting production of IL-23, troublesome work such as changing the taste and encapsulating can be saved. Of course, the taste of the composition for promoting production of IL-23 may be changed from other viewpoints, or the composition for promoting production of IL-23 may be encapsulated.
  • the microbial cells are preferably at least one of lactic acid bacteria and bifidobacteria.
  • lactic acid bacteria are Lactobacillus delbrueckiispsubsp. Bulgaricus, Lactobacillus gasseri, Streptococcus thermophilus (Streptococcus). It is preferably at least one lactic acid bacterium selected from the group consisting of thermophilus, Lactobacillus plantarum and Lactobacillus johnsonii.
  • lactic acid bacteria are “Lactobacillus delbrucky subspecies bulgaricus 2038, Lactobacillus delbrucky subspecies bulgaricus OLL1181 (Accession number: FERM BP- 11269), Lactobacillus delbrucky subspecies bulgaricus OLL1255 (Accession number: NITE BP-76), Lactobacillus delbrucky subspecies bulgaricus OLL1073R-1 (accession number: FERM BP-10741), lact Bacillus gasseri OLL2716 (Accession number: FERM BP-6999), Lactobacillus gaseri OLL2809 (Accession number: NITE BP-72), Lactobacillus gaseri OLL2 59 (Accession number: NITE BP-224), Lactobacillus plantarum OLL 2712 (Accession number: FERM BP
  • Lactobacillus delbruecki Subspecies Bulgarix OLL1255 (Accession number: NITE BP-76), Lactobacillus gaseri OL More preferably, it is at least one lactic acid bacterium selected from the group consisting of L2959 (Accession Number: NITE BP-224), Lactobacillus plantarum OLL2712 (FERM BP-11262), and Streptococcus thermophilus 1131.
  • the bifidobacteria is preferably Bifidobacterium bifidum.
  • Bifidobacterium is preferably Bifidobacterium bifidum OLB6378 (accession number: NITE BP-31).
  • the dendritic cells are tsDC, among the above-mentioned cells, cells that produce interleukin-23 at a concentration of 30 pg / mL or higher with respect to tsDC are preferable, and interleukins at a concentration of 50 pg / mL or higher are preferable. More preferably, microbial cells producing -23, more preferred microbial cells producing interleukin-23 at a concentration of 70 pg / mL or more, particularly preferred microbial cells producing interleukin-23 at a concentration of 90 pg / mL or more. .
  • the dendritic cell when the dendritic cell is tsDC, specifically, Lactobacillus delbruecki subspecies bulgaricus that produces interleukin-23 at a concentration of 30 pg / mL or more with respect to tsDC.
  • the dendritic cells are BMDC
  • cells that produce interleukin-23 at a concentration of 300 pg / mL or higher relative to BMDC are preferable, and interleukins at a concentration of 600 pg / mL or higher are preferable.
  • cells producing -23 more preferably cells producing interleukin-23 at a concentration of 900 pg / mL or more, more preferably cells producing interleukin-23 at a concentration of 1200 pg / mL or more.
  • Cells that produce interleukin-23 at a concentration of 1500 pg / mL or more are more preferred, and cells that produce interleukin-23 at a concentration of 2000 pg / mL or more are particularly preferred.
  • the dendritic cell is BMDC
  • Lactobacillus delbrukee subspecies bulgaricus that produces interleukin-23 at a concentration of 800 pg / mL or more with respect to BMDC
  • Lactobacillus delbruecki subspecies bulgaricus producing interleukin-23 at a concentration of 1000 pg / ml or more Lactobacillus delbruecki subspecies bulgaric producing interleukin-23 at a concentration of 1300 pg / ml or more Lactobacillus delbruecki subspecies bulgaricus producing interleukin-23 at a concentration of 1600 pg / ml or more
  • Streptococcus producing interleukin-23 at a concentration of 2000 pg / ml or more S.
  • thermophilus Lactobacillus gasseri that produces interleukin-23 at a concentration of 800 pg / mL or more, Lactobacillus gasseri that produces interleukin-23 at a concentration of 1000 pg / mL, or 1300 pg / mL or higher Lactobacillus gasseri that produces leukin-23, Lactobacillus gasseri that produces interleukin-23 at a concentration of 1600 pg / ml or more, Lactobacillus plantarum that produces interleukin-23 at a concentration of 1000 pg / ml or more, Lactobacillus plantarum producing interleukin-23 at a concentration of 1500 pg / mL or higher, Lactobacillus johnsonii producing interleukin-23 at a concentration of 300 pg / mL or higher, 800 pg / m Lactobacillus johnsonii producing interleuk
  • the method according to the second aspect of the present invention is a method of using bacterial cells as an IL-23 production promoter. That is, to provide a microbial cell for use as an IL-23 production promoter.
  • the method according to the third aspect of the present invention is a method of promoting IL-23 production in vivo by orally administering the above-mentioned composition for promoting IL-23 production.
  • the administration period is preferably 1 week or more, more preferably 2 weeks or more, further preferably 3 weeks or more, and particularly preferably 4 weeks or more.
  • the bacterial cells are brought into contact with dendritic cells. That is, the bacterial cells are brought into contact with dendritic cells to promote IL-23 production.
  • the use of the bacterial cell according to the fourth aspect of the present invention is an act for producing a composition for promoting the production of IL-23.
  • FIG. 3 is a bar graph showing IL-23 secretion amount (pg / mL) when tsDC is stimulated with various lactic acid bacteria heated dead cells.
  • FIG. 3 is a bar graph showing IL-23 secretion amount (pg / mL) when BMDC is stimulated with various lactic acid bacteria killed by heating.
  • FIG. 3 is a bar graph showing IL-23 secretion amount (pg / mL) when BMDC was stimulated with various lactic acid bacteria and Bifidobacterium heat-killed cells.
  • the composition for promoting IL-23 production contains microbial cells as an active ingredient.
  • the bacterial cell may be a live cell or a dead cell.
  • the dead cells are preferably heat-killed cells.
  • the term “heat-dead cell” is an object after the cell is killed by heating.
  • this IL-23 production promoting composition may consist only of microbial cells or may contain other components.
  • microbial cells can include, for example, lactic acid bacteria, bifidobacteria, and the like. Lactic acid bacteria are a general term for taxonomically recognized lactic acid bacteria or all related bacteria, and there are no restrictions on bacterial species or strains.
  • bifidobacteria is a generic term for taxonomically recognized bifidobacteria or all of the related bacteria, and there is no restriction on the bacterial species or strains.
  • lactic acid bacteria may be classified into plant origin and animal origin depending on their origin, the lactic acid bacteria of the present invention can be used from both plant origin and animal origin.
  • the lactic acid bacteria are Lactobacillus delbrueckii subsp. Bulgaricus, Lactobacillus gasseri, Streptococcus thermophilus (Streptococcus ⁇ ⁇ ⁇ thermophilus), More preferably, it is at least one lactic acid bacterium selected from the group consisting of Lactobacillus plantarum and Lactobacillus johnsonii.
  • Lactobacillus delbruecki subspecies bulgaricus Lactobacillus delbrucky subspecies bulgaricus 2038, Lactobacillus delbrucky subspecies bulgaricus OLL1181 (Accession number: FERM BP- 11269), Lactobacillus delbruecki subspecies bulgaricus MEP201701, Lactobacillus delbrucky subspecies bulgaricus OLL1255 (Accession number: NITE BP-76), Lactobacillus delbrucky subspecies bulgaricus OLLG1073R -1 (accession number: FERM BP-10741), and in the case of Lactobacillus gasseri, Re-OLL 2716 (Accession number: FERM BP-6999), Lactobacillus gaselli OLL2809 (Accession number: NITE BP-72), Lactobacillus gaseri OLL2959 (Accession
  • the Bifidobacterium is preferably Bifidobacterium bifidum.
  • the Bifidobacterium bifidum is preferably Bifidobacterium bifidum OLB6378 (Accession number: NITE BP-31), Bifidobacterium bifidum MEP201804.
  • Lactobacillus delbruecki subspecies bulgaricus 2038 can be obtained by isolating it from Bulgarian yogurt LB81 (registered trademark) manufactured by Meiji Co., Ltd. by a usual method.
  • Lactobacillus delbruecki subspecies bulgaricus MEP201701 can be obtained by isolation from fermented milk from the Republic of Bulgaria by a conventional method.
  • Lactobacillus delbruecki Subspecies Bulgarix OLL1255 was issued on February 10, 2005 (original deposit date), and is based on the Patent Microorganism Depositary Center of the National Institute of Technology and Evaluation (Kazusa Kama, Kisarazu City, Chiba Prefecture, Japan).
  • NITE BP-76 has been deposited internationally under the Budapest Treaty (transferred from the original deposit to the deposit under the Budapest Treaty on April 1, 2009).
  • Lactobacillus delbruecki Subspecies Bulgarix OLL1073R-1 was established on February 22, 1999 (date of domestic consignment), National Institute of Advanced Industrial Science and Technology, Biological Depositary Center (East 1 in Tsukuba City, Ibaraki Prefecture, Japan) No. 1 Chome No. 1 (Chuo No. 6) (later centralized in the Patent Microorganism Deposit Center of the National Institute of Technology and Evaluation (Kazusa-Kamazu 2-5-8, No.
  • Lactobacillus gaselli OLL2716 was dated May 24, 1999 (original deposit date), and the Institute of Biotechnology, Institute of Industrial Technology, Ministry of International Trade and Industry (1-3 Higashi 1-chome, Tsukuba, Ibaraki, Japan) Independent administrative agency, Product Evaluation Technology Foundation, Patent Microorganism Deposit Center (Centralized in Room 122, 2-5-8, Kazusa Kamashizu, Kisarazu City, Chiba, Japan), under the accession number: FERM BP-6999, based on the Budapest Treaty Deposited (transferred from the original deposit to the deposit under the Budapest Treaty on January 14, 2000).
  • Lactobacillus gaselli OLL2809 dated February 1, 2005 (original deposit date), is the Patent Microorganisms Depositary Center for Product Evaluation Technology, Japan (2-5-8 Kazusa Kamashi, Kisarazu City, Chiba Prefecture, Japan) 122 Room No.) has been deposited internationally under the Budapest Treaty under the deposit number: NITE BP-72 (transferred from the original deposit to the deposit under the Budapest Treaty on January 18, 2006).
  • Lactobacillus gaselli OLL2959 dated March 31, 2006 (original deposit date), National Institute for Product Evaluation Technology Patent Microorganisms Deposit Center (2-5-8 Kazusa Kamashika, Kisarazu City, Chiba Prefecture, Japan) 122 No.
  • Lactobacillus gasseri MEP201801 can be obtained by isolation from normal feces of healthy adults by conventional methods.
  • Streptococcus thermophilus 1131 can be obtained by isolation from Bulgarian yogurt LB81 (registered trademark) manufactured by Meiji Co., Ltd. according to a conventional method.
  • Streptococcus thermophilus MEP201702 can be isolated and obtained from fermented milk from the Republic of Bulgaria by a conventional method.
  • Lactobacillus plantarum OLL 2712 was issued on July 2, 2010, National Institute of Advanced Industrial Science and Technology, Biological Depositary Center (1st, 1st East, 1-chome, Tsukuba, Ibaraki, Japan) Incorporated internationally under the Budapest Treaty under the accession number: FERM BP-11262, which is centralized in the Patent Product Depositary Center of the National Institute for Product Evaluation and Technology (centralized at 2-5-8, Kazusa-Kamashita 2-5-8, Kisarazu City, Chiba, Japan) Yes. Lactobacillus plantarum MEP201802 can be obtained by isolation from raw milk from Hokkaido by a conventional method.
  • Lactobacillus johnsonii OLL203565 was issued on February 3, 2015 at the Japan Institute for Product Evaluation Technology Patent Microorganism Depositary Center (Kazusa Kamashichi, Kisarazu City, Chiba Prefecture, 2-5-8, Room 122). Deposit number: NITE BP-02003 is deposited internationally based on the Budapest Treaty.
  • Lactobacillus johnsonii OLL204255 was issued on February 3, 2015 in the National Institute for Product Evaluation Technology Patent Microorganism Depositary Center (Room 2-5-8, Kazusa Kamashichi, Kisarazu City, Chiba, Japan). Deposit number: NITE BP-02004 is deposited internationally based on the Budapest Treaty.
  • Lactobacillus johnsonii MEP201803 can be obtained by isolation from a dogwood pod that inhabits the mountains of Kanagawa Prefecture by a conventional method.
  • Bifidobacterium bifidum OLB6378 was commissioned on October 26, 2004 by the National Institute for Product Evaluation Technology Patent Microorganisms Deposit Center (2-5-8 Kazusa Kamashika, Kisarazu City, Chiba Prefecture, Japan). Number: NITE BP-31 is deposited internationally based on the Budapest Treaty.
  • Bifidobacterium bifidum MEP201804 can be obtained by isolation from healthy adult feces by conventional methods.
  • the form of the cells can be used even if it is frozen or freeze-dried.
  • the microbial cells may be in a form in which only the microbial cells or components other than the microbial cells (for example, cryoprotectants, lyophilization protectants, etc.) are included.
  • it may be dispersed in various media such as starch and water that have been used.
  • the IL-23 production promoting composition according to the embodiment of the present invention exhibits its function when taken by mammals including humans.
  • the “intake” as used herein is not limited to the administration route as long as it enters the human body, and is realized by all known administration methods such as oral administration, tube administration, enteral administration and the like. obtain. In this case, typical examples include oral intake and enteral intake via the digestive tract, but oral intake is preferable, and intake by eating and drinking is more preferable.
  • the composition for promoting IL-23 production according to the embodiment of the present invention may be any microorganism as long as it contains bacteria, and the number thereof is not particularly limited, but there are 100 million or more bacteria per unit package. Preferably, 500,000 or more are present, more preferably 1 billion or more. The effect can be expected as the number of cells increases, but the upper limit is 10 trillion.
  • the weight per unit packaging of the IL-23 production promoting composition according to the embodiment of the present invention is not particularly limited, but when there are 100 million or more cells per gram of the IL-23 production promoting composition,
  • the weight is preferably in the range of 10 to 500 g, more preferably in the range of 25 to 250 g, more preferably in the range of 50 to 200 g, and in the range of 75 to 150 g. Most preferably.
  • the above-mentioned unit packaging is not limited to unit packaging per bag, box, and container, but may be unit packaging per one time included therein or unit packaging per day. It should be noted that a plurality of days, for example, a quantity suitable for intake for one week may be packaged together, or may include a plurality of individual packages.
  • the composition for promoting IL-23 production is desirably ingested continuously for 3 weeks or more, preferably 5 weeks or more, more preferably 8 weeks or more.
  • the ingestion period is not particularly limited and can be permanently continued. From the viewpoint of obtaining a sufficiently effective IL-23 production effect, the intake period is preferably 8 weeks.
  • the composition for promoting IL-23 production according to the embodiment of the present invention can be used as a pharmaceutical or a food or drink.
  • the medicinal product or food or drink is useful in that it has an IL-23 production promoting effect, and can be used, for example, as a medicinal product or food or drink for preventing or treating microbial infection.
  • the composition for promoting IL-23 production according to the embodiment of the present invention is used as a pharmaceutical product or a food or drink, the cells of a single strain may be used, or the cells of two or more strains may be used. You may use it in combination.
  • the state of the IL-23 production promoting composition is not limited, and it is a pasty product, a spray-dried product, or a freeze-dried product.
  • the product can be used in the form of a product, a vacuum dried product, a drum dried product, a liquid product dispersed in a medium, a diluted product diluted with a diluent, a crushed product obtained by crushing a dried product with a mill or the like.
  • the composition for promoting IL-23 production according to the embodiment of the present invention can be used as a health functional food or a food for the sick.
  • the functional health food system is intended for not only regular foods but also foods in the form of tablets, capsules, etc., taking into account trends in Japan and overseas and the consistency with conventional food systems for specified health use. .
  • two types of foods for specific health use (individual permission type) and functional foods (standard specification type) are defined.
  • the composition for promoting production of IL-23 according to the embodiment of the present invention is administered to animals such as humans as special-purpose foods such as foods for specified health use or nutritional functional foods, thereby preventing various infections, for example. Is possible.
  • the IL-23 production promoting composition it is preferable to display a description of its use, efficacy, function, type of active ingredient, type of functional ingredient, ingestion method, and the like.
  • “Indication” as used herein refers to pharmaceuticals, quasi drugs, health functional foods, foods for specified health use, functional foods for nutrition, general foods, health supplements, health foods, supplements, enteral nutrition, oral cosmetics, and feed Each should be a suitable display.
  • the “display” here includes all displays for informing the consumer of the above description.
  • This display only needs to be a display that allows the above-described display contents to be recalled / analogized, and may include any display regardless of the purpose of display, the display contents, the object / medium to be displayed, and the like. For example, display the above description on product packaging / containers, display the above description on product advertisements / price lists or transaction documents, or display or distribute the information, electromagnetically (such as the Internet) ) By a method.
  • the product obtained by packaging the composition for promoting IL-23 production is, for example, a food or drink
  • the food or drink includes, for example, an indication “for IL-23 production promotion”
  • the label “contains lactic acid bacteria that promotes the production of IL-23”, the label “for antibacterial peptide enhancement”, the label “for prevention of infectious diseases”, etc. Is preferred.
  • the wording used for the display as described above is not limited to the above-described example, and may be a word having the same meaning as that.
  • various terms that allow the consumer to recognize IL-23 production promotion, antibacterial peptide enhancement, infection prevention effects, and the like can be accepted.
  • the type of the food or drink is not particularly limited.
  • Foods and beverages include, for example, milk, processed milk, soft drinks, fermented milk, yogurt, cheese, other dairy products, bread, biscuits, crackers, pizza crusts, prepared powdered milk, liquid food, food for the sick, infant milk powder, etc. It may be food, food such as powdered milk for pregnant women and lactating women, and nutritional food.
  • the bacterial cells that are the active ingredients of the IL-23 production promoting composition according to the embodiment of the present invention are used as they are, or mixed with other foods and drinks or food ingredients.
  • the manufacturing method in a normal food composition can be used. Moreover, it does not specifically limit about the shape of food / beverage products, The shape of food / beverage products used normally may be sufficient. For example, any shape such as solid (including powder and granule), paste, liquid, and suspension may be used, but not limited thereto. At this time, milk drink, fermented milk, soft drink, jelly drink, tablet, and powdered food are more preferable, and yogurt is more preferable.
  • the cells that are active ingredients of the composition for promoting IL-23 production according to the embodiment of the present invention include water, protein, carbohydrate, lipid, vitamins, minerals, organic acid, organic base, fruit juice, and flavor. As long as it is a component contained in normal foods such as functional ingredients and food additives, it can be added without any problem.
  • protein sources for example, whole milk powder, skim milk powder, partially skim milk powder, casein, whey powder, whey protein, whey protein concentrate, whey protein isolate, ⁇ -casein, ⁇ -casein, ⁇ -Uses proteins or protein-containing raw materials commonly used in food production, such as casein, ⁇ -lactoglobulin, ⁇ -lactalbumin, lactoferrin, soy protein, chicken egg protein, meat protein, and other hydrolysates can do.
  • sugar sources include processed starch (in addition to text phosphorus, soluble starch, British starch, oxidized starch, starch ester, starch ether, etc.), dietary fiber, and the like.
  • Examples of the lipid source include animal oils such as lard and fish oil, fractionated oils thereof, hydrogenated oil and transesterified oil; palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, and fractionated oils thereof. And vegetable oils such as hydrogenated oil and transesterified oil.
  • vitamins include vitamin A, carotenes, 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.
  • Examples of minerals 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.
  • Examples of the functional component include oligosaccharide, glucosamine, collagen, ceramide, royal jelly, polyphenol and the like.
  • Examples of food additives include emulsifiers, stabilizers, thickeners, gelling agents, sweeteners, acidulants, preservatives, antioxidants, pH adjusters, and colorants.
  • Various milk-derived components such as butter, dairy minerals, cream, whey, non-protein nitrogen, sialic acid, phospholipid, and lactose can be suitably used for the production of the food and drink according to the embodiment of the present invention. It is an example.
  • the raw material may be any of natural products, processed natural products, synthetic products and / or foods containing a large amount thereof.
  • the bacterial cell that is the active ingredient of the composition for promoting IL-23 production according to the embodiment of the present invention can be used as a drug for preventing infection or a drug for treatment.
  • the bacterial cell can be used as a crushed or unground product.
  • the microbial cell to be used may be single or multiple types.
  • the amount of bacterial cells in the above pharmaceutical product can be arbitrarily determined according to the purpose and application (prophylactic agent, therapeutic agent, etc.).
  • An example of the content may be 0.001 to 100% (w / w), particularly 0.1 to 100%, based on the total amount, but the present invention is not limited to this.
  • the dosage of the pharmaceutical agent containing the above bacterial cells as an active ingredient can be appropriately set in consideration of various factors such as the administration route, the age, weight, and symptoms of animals to be administered including humans.
  • a suitable dose 1 to 1000 mg / kg / day can be mentioned as an active ingredient, but the present invention is not limited to this.
  • the amount when ingested for preventive purposes over a long period, the amount may be smaller than the above range.
  • this active ingredient since this active ingredient has no safety problem, it can be used in a larger amount than the above range.
  • the above-mentioned pharmaceutical dosage form is preferably a dosage form that can be administered orally in order to allow the cells of the present invention to reach the intestine.
  • Examples of preferable dosage forms of the pharmaceutical product according to the present invention include tablets, coated tablets, capsules, granules, powders, liquids, syrups, lozenges and the like.
  • These various preparations are prepared according to conventional methods, such as excipients, binders, disintegrants, lubricants, coloring agents, flavoring agents, solubilizing agents, suspension agents, coating agents, etc. It can be formulated by mixing adjuvants that can be usually used in the pharmaceutical preparation technical field.
  • the microbial cells can be administered (ingested) as they are.
  • the microbial cells can be administered (ingested) as they are.
  • tablets, granules, powders Can be used as a capsule or powder.
  • the composition for promoting the production of IL-23 according to the embodiment of the present invention can be expected to exhibit effects at all sites of the digestive tract.
  • the digestive tract is a site including a series of oral cavity, pharynx, esophagus, stomach, duodenum, small intestine, large intestine, cecum, and anus.
  • typical names of the digestive tract are illustrated.
  • the colon lower small intestine
  • ileum jejunum
  • upper abdominal digestive tract lower abdominal digestive tract
  • large intestine lower large intestine
  • the composition for promoting IL-23 production according to the embodiment of the present invention is effective for all mammals including humans. Therefore, various diseases can be treated or prevented by ingesting and / or administering this IL-23 production promoting composition.
  • Mammals as used herein include humans, cows, pigs, sheep, dolphins, whales, tigers, lions, cheetahs, hippos, giraffes, camels, alpaca, dogs, cats, monkeys, foxes, raccoons, bears, squirrels, fur seals , Sea lions, pandas, wild boars, deer, horses, orangutans, kangaroos, etc., which are all known livestock, pets, appreciation animals, wild animals and the like and classified as mammals.
  • the composition for promoting IL-23 production according to the embodiment of the present invention is also applied to animals having a digestive tract, such as insects, reptiles, birds, fishes, amphibians, molluscs and the like. Administration and / or ingestion is also possible, and it is expected that the same effects as described above can be obtained.
  • the various diseases referred to herein are not particularly limited, and may be any diseases that can be treated and / or prevented by inducing an antibacterial peptide, for example.
  • diseases include infections caused by opportunistic bacteria, infections caused by pathogenic bacteria and fungi, infections caused by Helicobacter pylori, bacterial translocation, persistent intestinal mucosal inflammation, and changes in the balance of intestinal flora (intestinal Internal flora balance), diseases induced by these inflammations, Crohn's disease, inflammatory colitis such as ulcerative colitis, excessive inflammation and allergic symptoms that induce differentiation of regulatory T cells It is done.
  • Example 1 Preparation of heat-killed lactic acid bacteria
  • Bulgaricus 2038 Lactobacillus delbrueckii subsp.
  • Bulgaricus MEP201701 Lactobacillus delbrueckii subsp.
  • Bulgaricus OLL1255 (Accession number: NITE BP-76) ⁇ Lactobacillus delbrueckii subsp.
  • each medium was washed with phosphate buffered saline (PBS). And the turbidity of the washing
  • cleaning liquid was measured with wavelength 650nm with the spectrophotometer, and lactic acid bacteria suspension was prepared so that OD might be set to 2. Finally, each lactic acid bacterium suspension was incubated in a 65 ° C. hot water bath for 1 hour to prepare a target lactic acid bacterium heat-killed cell.
  • PBS phosphate buffered saline
  • BMDC bone marrow-derived dendritic cells
  • auto MACS registered trademark
  • Balb / c mice 8-week-old male Balb / c mice (provided by SLC, Japan)
  • GM-CSF granulocyte macrophage colony-stimulating factor
  • tsDC When tsDC is used as a dendritic cell, all of the nine strains of lactic acid bacteria are used.
  • BMDC When a dendritic cell, the nine strains of lactic acid bacteria are used. Among them, only heat-killed cells of Lactobacillus delbruecki subspecies bulgaricus 2038 and Streptococcus thermophilus 1131 were used.
  • Control sample preparation Dendritic cells were seeded in a 24-well plate so that the dendritic cells were 1 ⁇ 10 5 cells / well and the liquid volume was 500 ⁇ L, and the next day, 5 ⁇ L of phosphate buffered saline (PBS) was added to each well. ) was added. Thereafter, tsDC dendritic cells were cultured for 24 hours at 33 ° C. in a 9% CO 2 environment, and BMDCs were incubated for 24 hours at 37 ° C. in a 5% CO 2 environment. At this time, three samples were prepared for each of tsDC dendritic cells and BMDC. And the supernatant was collect
  • PBS phosphate buffered saline
  • Example 2 Preparation of heat-killed cells
  • 11 strains of lactic acid bacteria and 2 strains of bifidobacteria were prepared.
  • Bulgaricus OLL1073R-1 accesion number: FERM BP-10741
  • Bulgaricus OLL1181 accesion Number: FERM BP-11269
  • each medium was stored in a jar containing an anero pack, and each lactic acid bacterium and bifidobacteria were activated and cultured once at 37 ° C. in an anaerobic environment.
  • each medium was washed with phosphate buffered saline (PBS). Then, the turbidity of the washing solution was measured with a spectrophotometer at a wavelength of 650 nm, and a lactic acid bacterium suspension and a bifidobacteria suspension were prepared so that the OD was 2.
  • PBS phosphate buffered saline
  • each lactic acid bacterium suspension and bifidobacteria suspension were incubated in a hot water bath at 65 ° C. for 1 hour to prepare target lactic acid bacterium heated dead cells and bifidobacteria heated dead cells.
  • BMDC bone marrow-derived dendritic cells
  • Control sample preparation A control sample was prepared according to the same procedure as described in “4. Preparation of Control Sample” in Example 1.
  • composition for promoting production of interleukin-23 according to the present invention can save troublesome work such as changing the taste and encapsulating, and can be produced at low cost.

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Abstract

La présente invention concerne une composition favorisant la production d'interleukine-23 qui permet d'éliminer des procédures lourdes telles que l'encapsulation et la modification d'arôme. La composition favorisant la production d'interleukine-23 selon la présente invention contient des bactéries à titre de principe actif. Les bactéries à utiliser sont de préférence d'au moins un type choisi dans le groupe constitué par Lactobacillus delbrueckii ssp. Bulgaricus, Lactobacillus gasseri, Streptococcus thermophilus, Lactobacillus plantarum, Lactobacillus johnsonii, et Bifidobacterium bifidum.
PCT/JP2018/005414 2017-02-17 2018-02-16 Composition et procédé favorisant la production d'interleukine-23 WO2018151245A1 (fr)

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JP2024100172A JP2024111238A (ja) 2017-02-17 2024-06-21 インターロイキン－２３産生促進用組成物およびＲｅｇ３ファミリータンパク質の発現誘導用組成物

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Citations (1)

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WO2011145737A1 (fr) 2010-05-21 2011-11-24 株式会社明治 Composition pour améliorer l'état de la peau
TWI572354B (zh) 2010-09-09 2017-03-01 明治股份有限公司 抑制發炎之組成物
WO2015087919A1 (fr) 2013-12-10 2015-06-18 株式会社明治 Agent inducteur de peptide antibactérien
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