WO2021261423A1 - インターロイキン－１０の産生促進用組成物 - Google Patents

インターロイキン－１０の産生促進用組成物 Download PDF

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Publication number
WO2021261423A1
WO2021261423A1 PCT/JP2021/023326 JP2021023326W WO2021261423A1 WO 2021261423 A1 WO2021261423 A1 WO 2021261423A1 JP 2021023326 W JP2021023326 W JP 2021023326W WO 2021261423 A1 WO2021261423 A1 WO 2021261423A1
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Prior art keywords
lactic acid
fermented milk
composition
lactobacillus
production
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Ceased
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PCT/JP2021/023326
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English (en)
French (fr)
Japanese (ja)
Inventor
孝之 利光
良尚 河合
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Meiji Co Ltd
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Meiji Co Ltd
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Priority to CN202180044666.5A priority Critical patent/CN115916230A/zh
Priority to JP2022531961A priority patent/JPWO2021261423A1/ja
Priority to EP21828789.4A priority patent/EP4212165A4/en
Priority to US18/012,112 priority patent/US20230293605A1/en
Publication of WO2021261423A1 publication Critical patent/WO2021261423A1/ja
Anticipated expiration legal-status Critical
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    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; PREPARATION THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
    • 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
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/20—Milk; Whey; Colostrum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/11—Lactobacillus
    • A23V2400/157—Lactis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/225—Lactobacillus
    • C12R2001/25—Lactobacillus plantarum

Definitions

  • FIG. 3 shows the IL-10 production of the composition of the fermented milk containing the heated bacterium of the Lactobacillus lactic acid bacterium OLL2712 strain and the fermented milk not containing the heated bacterium of the Lactobacillus lactic acid bacterium OLL2712 strain for each cooling and stirring condition. It is a graph which shows the result of the multiple comparison test by the Tukey-Kramer method of the promotion activity.
  • composition of the present invention may contain components other than lactic acid bacteria of the genus Lactobacillus and fermented milk as long as the effects of the present invention are not impaired.
  • Ingredients other than lactobacillus lactic acid bacteria and fermented milk include, for example, medium components, additives suitable for oral tube ingestion, solvents such as water, sugars, proteins, lipids, vitamins, minerals, and essential trace metals for living organisms. (Manganese sulfate, zinc sulfate, magnesium chloride, potassium carbonate, etc.), fragrances, food hygiene or pharmaceutically acceptable carriers, food additives, etc. may be mentioned.
  • display means all actions for informing the consumer of the above-mentioned use, and if the display can recall or infer the above-mentioned use, the purpose and display of the display. Regardless of the content, the object to be displayed, the medium, etc., all of them fall under the "display" of the present invention. However, it is preferable to display it in an expression that allows the consumer to directly recognize the above-mentioned use.
  • the display is approved by the government or the like (for example, a display obtained based on various systems established by the government and performed in a manner based on such approval).
  • the display is approved by the government or the like (for example, a display obtained based on various systems established by the government and performed in a manner based on such approval).
  • labeling as health foods, functional foods, foods with functional claims, enteral nutrition foods, special-purpose foods, foods for the sick, nutritionally functional foods, non-medicinal products, etc. can be exemplified, and other welfare.
  • Labels approved by the Ministry of Labor for example, foods for specified health use, and labels approved by a similar system can be exemplified.
  • the pharmaceutical composition is prepared by preparing the composition of the present invention as an oral preparation or a parenteral preparation according to a conventional method.
  • the formulation may be combined with an acceptable additive for the formulation.
  • Acceptable additives for formulation include, for example, excipients, stabilizers, preservatives, wetting agents, emulsifiers, lubricants, sweeteners, colorants, fragrances, buffers, antioxidants, pH. Examples include adjusting agents.
  • the pharmaceutical composition is an oral preparation, it is a solid preparation such as tablets, powders, fine granules, granules, capsules, pills and sustained-release agents, and liquid preparations such as solutions, suspensions and emulsions. It can take the form.
  • the pharmaceutical composition is a parenteral preparation, it can be in the form of an injection or a suppository. From the viewpoint of simplicity of ingestion (administration) to the ingestion target, the pharmaceutical composition is preferably an oral preparation.
  • an anti-inflammatory composition containing a lactic acid bacterium belonging to the genus Lactobacillus and fermented milk is provided.
  • a method for producing a composition for promoting IL-10 production which comprises the following steps: Starter inoculation process to obtain fermented milk base material by inoculating raw milk with starter, Fermentation step of fermenting the fermented milk base material to obtain fermented milk, A step of adding lactic acid bacteria to obtain fermented milk containing lactic acid bacteria by adding lactic acid bacteria belonging to the genus Lactobacillus to the fermented milk, and A stirring step of stirring at least one selected from the group consisting of the fermented milk and the fermented milk containing lactic acid bacteria.
  • the same lactic acid bacterium belonging to the genus Lactobacillus contained in the composition for promoting the production of interleukin-10 can be used.
  • the lactic acid bacterium belonging to the genus Lactobacillus is preferably Lactobacillus plantarum, and more preferably the Lactobacillus plantarum OLL2712 strain.
  • a culture solution, a concentrated culture solution, a freeze-concentrated bacterium, a frozen pellet, a freeze-dried powder, or the like can be used.
  • the amount of Lactobacillus lactic acid bacteria added to the raw milk, fermented milk base material and / or fermented milk is, for example, 0 with respect to the total mass of the raw milk, fermented milk base material or fermented milk to which Lactobacillus lactic acid bacteria are added. It is 0.01% by mass or more, 0.01 to 15% by mass, 0.02 to 10% by mass, 0.03 to 5% by mass, and particularly preferably 0.03 to 1% by mass.
  • the range of the average particle size of the fermented milk after stirring is preferably 0.5 to 100 ⁇ m, more preferably 1 to 50 ⁇ m, more preferably 5 to 50 ⁇ m, still more preferably 10 to 25 ⁇ m, and particularly preferably 15 to 25 ⁇ m. can do.
  • the average particle size of the fermented milk containing Lactobacillus lactic acid bacteria can be measured by the same method as the above-mentioned measurement of the average particle size of fermented milk in the composition of the present invention.
  • the production method of the present invention may further include a cooling step of cooling the lactic acid bacterium-containing composition.
  • the lactic acid bacterium-containing composition is cooled to a temperature lower than the fermentation temperature range (for example, 30 to 60 ° C.), for example, 15 ° C. or lower.
  • the lactic acid bacterium-containing composition is cooled to preferably 1 to 15 ° C, more preferably 3 to 12 ° C, and even more preferably 5 to 10 ° C.
  • the cooling method (cooling condition) is not particularly limited, and it may be cooled rapidly by ice cooling or the like, or may be cooled slowly by a thermostat such as a refrigerator or a thermostatic chamber.
  • the cooling step may be performed alone or in parallel with the stirring step described above. From the viewpoint of increasing the production efficiency of the composition and increasing the IL-10 production promoting activity in the obtained composition, it is preferable that the cooling step is performed in parallel with the stirring step.
  • the stirring condition and the cooling condition when the stirring step and the cooling step are performed in parallel the same conditions as described in the stirring step and the cooling step can be adopted, respectively.
  • the target of application of the combination of Lactobacillus genus lactic acid bacteria and fermented milk is not particularly limited as long as it is a target for which it is necessary to promote the production of IL-10, and may be a healthy person, and IL-10. Those who have decreased production and those who have a tendency to decrease IL-10 production may be used.
  • Diseases caused by inflammation are not particularly limited, and examples thereof include metabolic syndrome, dyslipidemia, diabetes, obesity, hyperglycemia, cancer, and autoimmune diseases. Therefore, another embodiment of the genus Lactobacillus for treating and / or preventing a disease selected from the group consisting of metabolic syndrome, dyslipidemia, diabetes, obesity, hyperglycemia, cancer and autoimmune diseases.
  • a disease selected from the group consisting of metabolic syndrome, dyslipidemia, diabetes, obesity, hyperglycemia, cancer and autoimmune diseases.
  • compositions containing lactic acid bacteria and fermented milk are examples thereof.
  • an effective amount of a composition comprising Lactobacillus lactic acid bacteria and fermented milk is applied to a subject in need thereof to promote the production of IL-10 in the subject.
  • the method is provided.
  • an effective amount of a composition containing Lactobacillus genus Lactobacillus and fermented milk is applied to a subject in need thereof, which is caused by inflammation in the subject.
  • a method of controlling the disease is provided.
  • “suppression” includes not only the concept of treating an established pathological condition but also the concept of preventing a pathological condition that may be established in the future.
  • a composition containing Lactobacillus lactic acid bacteria and fermented milk for the production of foods and drinks for the treatment of diseases caused by a decrease in IL-10 production.
  • the disease caused by the decrease in the production amount of IL-10 is inflammation, a disease caused by inflammation, and the like. Therefore, one embodiment is the use of a composition comprising Lactobacillus lactic acid bacteria and fermented milk for the production of foods and drinks for the treatment of inflammation. Yet another embodiment is the use of a composition comprising Lactobacillus lactic acid bacteria and fermented milk for the production of foods and drinks for the treatment of diseases caused by inflammation.
  • Diseases caused by inflammation are not particularly limited, and examples thereof include metabolic syndrome, dyslipidemia, diabetes, obesity, hyperglycemia, cancer, and autoimmune diseases. Therefore, another embodiment is for the production of foods and drinks for the treatment of diseases selected from the group consisting of metabolic syndrome, dyslipidemia, diabetes, obesity, hyperglycemia, cancer and autoimmune diseases. Use of compositions containing Lactobacillus lactic acid bacteria and fermented milk.
  • Diseases caused by inflammation are not particularly limited, and examples thereof include metabolic syndrome, dyslipidemia, diabetes, obesity, hyperglycemia, cancer, and autoimmune diseases.
  • another embodiment comprises applying an effective amount of a composition comprising Lactobacillus lactic acid bacteria and fermented milk to a subject in need thereof, including metabolic syndrome, dyslipidemia, diabetes in the subject.
  • the heat treatment of the lactic acid bacterium Lactobacillus plantarum OLL2712 strain was carried out by concentrating the cells and then heating at 60 ° C. for 10 minutes.
  • the fermented milk was then slowly cooled to 4 ° C. in the refrigerator with stirring at 150 rpm. Then, the fermented milk was homogenized by a homomixer to obtain a drink yogurt.
  • the amount of cells of the lactic acid bacterium Lactobacillus plantarum OLL2712 strain contained in the fermented milk was 5 ⁇ 10 9 or more / 112 g.
  • BMDC bone marrow-derived dendritic cells
  • the obtained immature dendritic cells were cultured in 10 ml of RPMI-10 containing 10% GM-CSF, and 5 ml of RPMI-10 containing GM-CSF was added 3 days later. After another 5 days, floating cells were collected and used as BMDCs.
  • Lactobacillus starter A and heat-treated lactic acid bacterium Lactobacillus plantarum OLL2712 strain are added to raw milk (mixture containing raw milk, defatted milk powder, cream, sugar and stevia) until the pH reaches about 4.4 to 4.6 (pH 4.4 to 4.6). Fermented milk was prepared by fermenting the raw milk by keeping it at 43 ° C. (4 to 6 hours). The heat treatment of the lactic acid bacterium Lactobacillus plantarum OLL2712 strain was carried out by concentrating the cells and then heating at 60 ° C. for 10 minutes.
  • the amount of cells of the lactic acid bacterium Lactobacillus plantarum OLL2712 strain contained in the obtained fermented milk was 5 ⁇ 10 9 or more / 112 g.
  • the obtained fermented milk was divided into three groups, and the fermented milk in each group was cooled under the following conditions. Group 1: Stir with rapid cooling in ice cooling. Group 2: Stirring while slowly cooling in the refrigerator. Group 3: The mixture was allowed to stand in a refrigerator without stirring and slowly cooled. In the first group and the second group, stirring was performed at 150 rpm. Further, in the rapid cooling of the first group, it took about 20 minutes for the fermented milk to which lactic acid bacteria were added to reach 10 ° C. or lower. On the other hand, in the slow cooling of the second group and the third group, it took about 2 hours for the fermented milk containing lactic acid bacteria to reach 10 ° C. or lower.
  • Group 2 control fermented milk: Stirred while slowly cooling in the refrigerator.
  • Group 3 (fermented milk containing lactic acid bacteria): The milk was allowed to stand in a refrigerator without stirring and slowly cooled.
  • Group 4 (fermented milk containing lactic acid bacteria): Stirred while slowly cooling in a refrigerator.
  • Example 2 Confirmation of the effect of a composition containing Lactobacillus lactic acid bacteria and fermented milk on cytokines
  • the composition containing Lactobacillus genus lactic acid bacteria and fermented milk is an anti-inflammatory cytokine (IL-10) and an inflammatory cytokine (IL-12).
  • IL-10 anti-inflammatory cytokine
  • IL-12 inflammatory cytokine
  • the heat treatment of lactic acid bacteria was carried out by concentrating the cells and then heating at 60 ° C. for 10 minutes.
  • the amount of Lactobacillus lactic acid bacteria contained in the obtained fermented milk containing lactic acid bacteria was 5 ⁇ 10 9 or more / 112 g.
  • a control fermented milk hard yogurt was prepared in the same manner as the above-mentioned lactic acid bacterium-containing fermented milk except that the Lactobacillus lactic acid bacterium Lactobacillus plantarum OLL2712 strain was not added.
  • IL-10 production amount is the same as the measurement of the IL-10 production amount in Example 1 above, except that "Mouse IL-12 (p70) ELISA Set" (manufactured by Becton Dickinson) was used as an ELISA kit. Measured by method. Here, the production amount (concentration) of IL-12 was measured as the production amount (concentration) of IL-12 (p70), which is an active form.
  • composition containing Lactobacillus lactic acid bacteria and fermented milk increases the production promoting activity of IL-10, and further, in the composition containing Lactobacillus lactic acid bacteria and fermented milk, Lactobacillus lactic acid bacteria.
  • the production of IL-10 is synergistically promoted as compared with the composition containing fermented milk alone.
  • Preparation day of each composition except for adding 1% concentration in bone marrow-derived dendritic cells (10 5 cells / well), in the same manner as in Example 1, production of anti-inflammatory cytokine IL-10 was measured.
  • the amount of IL-12 produced is the same as the measurement of the amount of IL-10 produced in Example 1 above, except that "Mouse IL-12 (p70) ELISA Set" (manufactured by Becton Dickinson) was used as an ELISA kit. Measured by method.
  • the production amount (concentration) of IL-12 was measured as the production amount (concentration) of IL-12 (p70), which is an active form.
  • the results for the amount of IL-10 produced and the amount of IL-12 produced are shown in FIGS. 6A and 6B, respectively.
  • composition containing Lactobacillus genus Lactobacillus and fermented milk significantly increases the ratio of IL-10 amount / IL-12 amount, and further, the lactic acid bacterium Lactobacillus plantarum OLL2712 strain and fermented milk. It is suggested that the composition contained in the composition increases the ratio of IL-10 amount / IL-12 amount particularly significantly.
  • composition containing Lactobacillus genus Lactobacillus and fermented milk significantly increases the IL-10 production promoting activity, and further, the composition containing Lactobacillus lactobacillus plantarum OLL2712 strain and fermented milk. , It suggests that the IL-10 production promoting activity is particularly significantly increased.

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PCT/JP2021/023326 2020-06-22 2021-06-21 インターロイキン－１０の産生促進用組成物 Ceased WO2021261423A1 (ja)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CN202180044666.5A CN115916230A (zh) 2020-06-22 2021-06-21 用于促进白细胞介素-10产生的组合物
JP2022531961A JPWO2021261423A1 (https=) 2020-06-22 2021-06-21
EP21828789.4A EP4212165A4 (en) 2020-06-22 2021-06-21 COMPOSITION TO PROMOTE THE PRODUCTION OF INTERLEUKIN-10
US18/012,112 US20230293605A1 (en) 2020-06-22 2021-06-21 Composition for promoting production of interleukin-10

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JP2020107035 2020-06-22
JP2020-107035 2020-06-22

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WO2025224073A1 (en) 2024-04-25 2025-10-30 Slimbiotics Gmbh Use of lactobacillus bacteria for reducing adipose and promoting muscle tissue

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EP4104844A4 (en) * 2019-12-13 2024-02-14 Meiji Co., Ltd Composition for lowering heart rate
TW202241477A (zh) * 2020-12-16 2022-11-01 日商明治股份有限公司 腦組織之發炎改善用組成物

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