WO2012133827A1 - Nouvelle bactérie lactique et produit pharmaceutique, aliment ou boisson et aliment pour animaux contenant tous la nouvelle bactérie lactique - Google Patents

Nouvelle bactérie lactique et produit pharmaceutique, aliment ou boisson et aliment pour animaux contenant tous la nouvelle bactérie lactique Download PDF

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Publication number
WO2012133827A1
WO2012133827A1 PCT/JP2012/058690 JP2012058690W WO2012133827A1 WO 2012133827 A1 WO2012133827 A1 WO 2012133827A1 JP 2012058690 W JP2012058690 W JP 2012058690W WO 2012133827 A1 WO2012133827 A1 WO 2012133827A1
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Prior art keywords
strain
lactic acid
composition
mcc1375
lactobacillus paracasei
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English (en)
Japanese (ja)
Inventor
紀介 岩淵
金忠 清水
寿美子 米澤
幸子 高橋
村上　和也
伊藤　達也
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Morinaga Milk Industry Co Ltd
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Morinaga Milk Industry Co Ltd
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Priority to JP2012537042A priority Critical patent/JP5261617B2/ja
Publication of WO2012133827A1 publication Critical patent/WO2012133827A1/fr
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    • 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
    • A23C9/1234—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt characterised by using a Lactobacillus sp. other than Lactobacillus Bulgaricus, including Bificlobacterium sp.
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
    • A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
    • A23K10/18—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions of live microorganisms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • 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
    • A23V2400/165—Paracasei
    • 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
    • A61K2035/11—Medicinal preparations comprising living procariotic cells
    • A61K2035/115—Probiotics
    • 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

Definitions

  • the present invention relates to a novel lactic acid bacterium. Moreover, this invention relates to the pharmaceutical, food-drinks, and feed containing novel lactic acid bacteria.
  • Lactic acid bacteria are known to have various pharmacological actions and are widely used. For example, a lactic acid bacterium showing a preventive action and a therapeutic action for infectious diseases has been reported (Non-patent Document 1). It has been reported that the action of lactic acid bacteria is due to activation of cellular immunity of the host and enhancement of IgA secretion from mucous membranes such as the intestinal tract and respiratory organs.
  • lactic acid bacteria belonging to Lactobacillus casei stimulate cellular immunity of the host by inducing the production of cytokines such as IL-12 (interleukin-12) and IFN- ⁇ from the host immunocompetent cells.
  • cytokines such as IL-12 (interleukin-12) and IFN- ⁇ from the host immunocompetent cells.
  • IL-12 and IFN- ⁇ enhance the action of inducing differentiation of naive helper T cells into type 1 helper T cells (Th1), activation of natural killer cells (NK cells), and phagocytosis of cells such as macrophages. It is a cytokine with an action, and is considered to be involved in the protective action against viruses and bacteria and the antitumor effect of the host.
  • IL-12 is known to have an antitumor effect, an antimetastatic effect, an effect on infections such as opportunistic infections, and a prevention and treatment effect on allergic diseases such as asthma (Non-patent Document 5).
  • Lactobacillus paracasei KW3110 (FERM BP-08634) is known as a lactic acid bacterium having IL-12 production inducing ability (Patent Document 1). It has been reported that the amount of IL-12 produced by Lactobacillus paracasei KW3110 is 1.9 times that of Lactobacillus rhamnosus ATCC 53103 strain (GG strain) (Non-patent Document 6). In addition, Lactobacillus rhamnosus GG strain has been reported to prevent infection against influenza virus (Non-patent Document 7).
  • Non-patent Document 8 a study comparing the effects of lactic acid bacteria on intestinal mucosal immunity between live and dead bacteria, it is reported that live bacteria have a stronger effect on intestinal mucosal immunity than dead bacteria.
  • lactic acid bacteria exhibit various preferable pharmacological actions, and it is preferable that lactic acid bacteria are maintained as live bacteria and reach the intestinal mucosa.
  • beverages containing lactic acid bacteria are usually acidic beverages, and under these acidic conditions (low pH conditions), lactic acid bacteria are likely to die.
  • orally administered lactic acid bacteria are exposed to acidic gastric juice, they tend to die before reaching the intestinal mucosa.
  • an object of the present invention is to provide a novel lactic acid bacterium having a high survival rate under acidic conditions, and a medicine, food and drink, and feed containing the lactic acid bacterium.
  • the present inventors diligently searched for a novel lactic acid bacterium having a high survival rate under acidic conditions, and the Lactobacillus paracasei MCC1375 strain (this strain is incorporated into the Patent Organism Depositary, National Institute of Advanced Industrial Science and Technology). Was deposited as FERM BP-11313.) And the present invention was completed.
  • the Lactobacillus paracasei strain according to the present invention has higher survival under acidic conditions than conventional lactic acid bacteria, and further promotes IL-12 production and activates NK cells. Yes, it can suppress the growth of influenza virus and prevent symptoms caused by influenza virus, that is, it exhibits excellent infection prevention and infection protection.
  • the present invention also includes the following (1) to (11).
  • the composition according to (6), wherein the food or drink is fermented milk or a lactic acid bacteria beverage.
  • the composition according to (4), wherein the composition is a feed composition.
  • compositions for promoting production of interleukin-12 comprising the strain according to any one of (3) as an active ingredient.
  • a composition for NK cell activation comprising the strain according to any one of (3) as an active ingredient.
  • An anti-influenza virus composition comprising the strain according to any one of (3) as an active ingredient.
  • the present invention also includes the following (21) to (26).
  • (21) A medicament comprising Lactobacillus paracasei MCC1375 strain (FERM BP-11313).
  • (24) An anti-influenza virus agent containing Lactobacillus paracasei MCC1375 strain.
  • (26) Feed containing Lactobacillus paracasei MCC1375 strain.
  • the present invention also lies in an interleukin-12 production promoter, an NK cell activator, and an anti-influenza virus agent containing the above strain or composition as an active ingredient.
  • the acid survival is, for example, that the survival rate after storage for 4 weeks at 10 ° C. at pH 3.0 is 90% or more, or after storage for 6 weeks at 10 ° C. at pH 3.0, for example. It can be confirmed that the survival rate is 40% or more.
  • the present invention also includes the following (31) to (34).
  • the present invention also includes the following (41) to (44).
  • (41) A starter for producing fermented milk containing Lactobacillus paracasei MCC1375 strain.
  • the present invention is also in a method for obtaining a mutant strain using Lactobacillus paracasei MCC1375 strain.
  • Lactobacillus paracasei MCC1375 strain can be obtained by a known method using this strain as a starting material. It can confirm that it has the outstanding characteristic of this invention by performing the process which confirms acidic survivability (low pH survivability) with respect to this mutant. Further, a step of confirming the property of promoting interleukin-12 production, a step of confirming the property of NK cell activation, and / or a step of confirming the property of anti-influenza virus are performed on this mutant strain.
  • the composition can be used as a composition for promoting interleukin-12 production, a composition for NK cell activation, and / or an anti-influenza virus composition.
  • the present invention provides a novel lactic acid bacterium having a high survival rate under acidic conditions. Therefore, even when the novel lactic acid bacterium according to the present invention is contained in an acidic food or drink such as a lactic acid bacterium beverage, it is difficult to kill, and the beneficial effect of the live bacterium can be maintained over a long period of time. Furthermore, the novel lactic acid bacteria according to the present invention are resistant to acidic gastric juice even when orally administered in the form of foods and beverages and oral preparations, reach the intestinal mucosa with high survival, and are beneficial to live bacteria. The effect can be demonstrated.
  • the novel lactic acid bacterium according to the present invention has higher IL-12 production inducing ability, NK cell activity action, and anti-influenza virus action, compared with conventionally known lactic acid bacteria. It can be used as a composition for induction or a composition for NK cell activation, and more specifically, widely used as an antitumor agent, a prophylactic or therapeutic agent for opportunistic infections, a prophylactic agent for allergic diseases, or a therapeutic agent. be able to.
  • the novel lactic acid bacteria according to the present invention can be used as viable bacteria having high survival ability, can also be used as dead cells, and can be widely used in medicines, foods and drinks, and feeds.
  • Lactobacillus paracasei MCC1375 strain has a high ability to induce IL-12 production against mouse-derived lymphocytes and human-derived peripheral blood mononuclear cells (PBMC), even in dead cells, and is orally administered to mice. When administered, it induces an increase in NK cells and has a preventive action against influenza virus infection, and thus can be suitably used for the prevention and treatment of influenza virus.
  • PBMC peripheral blood mononuclear cells
  • FIG. 1 shows IL-12 production from human peripheral blood mononuclear cells by Lactobacillus paracasei MCC1375 strain.
  • FIG. 2 shows the proportion of NK cells in splenocytes when MCC1375 strain is administered to mice. * Indicates a statistically significant difference between the two groups.
  • FIG. 3 shows the influenza virus infection prevention effect of MCC1375 strain. * Indicates a statistically significant difference between the two groups. + Indicates a statistical trend between both groups.
  • A The symptom score after influenza virus infection is shown.
  • C Lung virus concentration after influenza virus infection.
  • MCC1375 strain as a novel lactic acid bacteria strain. This strain was isolated using human feces as the source of separation.
  • MCC1375 strain Cell morphology, 2. 2. mobility. Sporulation, 4. 4. Gram stainability, Catalase, 6. Table 1 shows the production of gas from glucose and sugar fermentability.
  • the sugar fermentability was measured using a bacterial identification kit API50CH (manufactured by bioMerieux Japan) according to the method described in the attached manual. That is, the culture solution of MCC1375 strain after overnight culture was inoculated into a medium containing each carbohydrate, cultured in an anaerobic glove box at 37 ° C., and the availability of each carbohydrate was judged on the seventh day from the start of the culture. did.
  • a list of mycological properties of the MCC1375 strain is shown in Table 1 below.
  • the entire region 1476 bp of 16S rRNA gene of MCC1375 strain was decoded by a known method.
  • the identification of strains can be found, for example, in "" Microbial Classification and Identification Experiments-Focusing on Molecular Genetics and Molecular Biology-", published by Springer Fairlark Tokyo, September 16, 2001. According to the method described (p.9-14, p.48-64, p.231-285 etc.), it was performed by analyzing the full length of 16S rRNA gene of various strains.
  • the base sequence of 1476 bp of the 16S rRNA gene of MCC1375 strain that was decrypted is casei from ATCC334 T strain and that had a 99.80% homology, have been shown to be Lactobacillus paracasei or Lactobacillus casei. Furthermore, the homology of the genome between the MCC1375 strain, the Lactobacillus paracasei standard strain (ATCC25302 T ), and the Lactobacillus casei standard strain (ATCC393 T ) was determined as Int. The homology with the Lactobacillus paracasei standard strain was 87% when confirmed by the DNA hybridization test described in J Systact Bacteriol, No. 39, pp.
  • Lactobacillus paracasei MCC1375 strain was incorporated into the National Institute of Advanced Industrial Science and Technology Patent Biological Deposit Center (Japan, 1-15-1 Higashi 1-1-1 Tsukuba City, Ibaraki Prefecture) from November 5, 2010 The deposit number is FERM BP-11313.
  • the Lactobacillus paracasei MCC1375 strain is not limited to the deposited strain, and may be a strain substantially equivalent to the deposited strain.
  • the strain substantially equivalent to the deposited strain is a strain belonging to Lactobacillus paracasei, has an acid survival property, preferably has a high IL-12 production promoting effect and a high antiviral effect, and further
  • the base sequence of the 16S rRNA gene preferably has 99.86% or more, more preferably 99.93% or more, more preferably 100% homology to the base sequence of the 16S rRNA gene of the deposited strain, and Preferably, it is a strain having the same mycological properties as the deposited strain.
  • stock can produce and use the mutant strain which mutated MCC1375 strain
  • known mutation means such as UV can be used.
  • the Lactobacillus paracasei MCC1375 of the present invention can be suitably used as a living bacterium because it has high survival, but even a dead bacterium can be preferably used.
  • the Lactobacillus paracasei MCC1375 strain used in the present invention can be easily propagated, for example, by culturing the above strain.
  • the method of culturing is not particularly limited as long as Lactobacillus paracasei MCC1375 strain can grow, and the method usually used for culturing lactic acid bacteria can be appropriately modified as necessary.
  • the culture temperature may be 25 ° C. to 50 ° C., preferably 35 ° C. to 42 ° C.
  • the culture can be performed under either aerobic conditions or anaerobic conditions. As an anaerobic condition, it can culture, for example, ventilating anaerobic gas, such as a carbon dioxide gas.
  • the medium for culturing Lactobacillus paracasei MCC1375 strain is not particularly limited, and a medium usually used for culturing lactic acid bacteria can be appropriately modified as necessary. That is, as the carbon source, for example, saccharides such as galactose, glucose, fructose, mannose, cellobiose, maltose, sucrose, trehalose, starch, starch hydrolyzate, and molasses can be used depending on the utilization. As the nitrogen source, for example, ammonium salts such as ammonia, ammonium sulfate, ammonium chloride, and ammonium nitrate, and nitrates can be used.
  • the carbon source for example, saccharides such as galactose, glucose, fructose, mannose, cellobiose, maltose, sucrose, trehalose, starch, starch hydrolyzate, and molasses can be used depending on the utilization.
  • the nitrogen source for example, am
  • inorganic salts examples include sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, and ferrous sulfate.
  • Organic components such as peptone, soybean powder, defatted soybean meal, meat extract, yeast extract and the like may also be used.
  • MRS medium can be suitably used as the prepared medium.
  • the obtained culture may be used as it is, diluted or concentrated, or cells recovered from the culture may be used.
  • additional operations such as heating and freeze-drying can be performed after culturing as long as the effects of the present invention are not impaired.
  • an additional operation an operation with a large ratio of remaining viable bacteria is preferable.
  • Lactobacillus paracasei MCC1375 strain can be widely used in medicine, food and drink, and feed.
  • the Lactobacillus paracasei MCC1375 strain can be used as an IL-12 production promoter, NK cell activator, and anti-influenza virus agent.
  • strains of novel lactic acid bacteria according to the present invention include mutant strains of the aforementioned Lactobacillus paracasei MCC1375 strain.
  • the novel strain of lactic acid bacteria according to the present invention is low pH survivability (acid survivability), specifically, for example, after storage for 4 weeks at 10 ° C. at pH 3.0. Or the survival rate after storage for 6 weeks at 10 ° C. at pH 3.0 is 40% or more.
  • pH survivability acid survivability
  • these storage conditions are determined by L. cerevisiae, a strain that appears to be closely related.
  • Rhamnosus ATCC 53103 strain, L. Paracasei ATCC 25302 T strain and L. All of the casei ATCC 393 T strains have a survival rate of less than 0.1% or below the detection limit.
  • the medicament of the present invention is not particularly limited as long as it contains the novel lactic acid bacterium strain according to the present invention, preferably Lactobacillus paracasei MCC1375 strain as an active ingredient.
  • the above strain may be used as it is, or a pharmaceutically acceptable liquid or solid preparation carrier may be blended and used as a preparation.
  • the above strains can be used whether they are live or dead.
  • the pharmaceutical dosage form of the present invention is not particularly limited, and specifically, tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, syrups, suppositories, injections, ointments , Patches, eye drops, nasal drops and the like.
  • addition of excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, diluents, surfactants, or injectable solutions that are commonly used as pharmaceutical carriers Agents can be used.
  • the content of the strain of the novel lactic acid bacterium according to the present invention, preferably the Lactobacillus paracasei MCC1375 strain in the medicament of the present invention is the dosage form, usage, patient age, sex, disease type, disease severity, and other Although it is appropriately set depending on conditions and the like, it is usually preferably in the range of 1 ⁇ 10 6 to 1 ⁇ 10 12 pieces / g and preferably in the range of 1 ⁇ 10 7 to 1 ⁇ 10 11 pieces / g More preferred.
  • the number of bacteria may be expressed as CFU (colony forming unit).
  • the above “pieces / g” can be expressed as “CFU / g” in living bacteria. In the dead cells of Examples, 1 ⁇ g corresponds to 3.75 ⁇ 10 6 , and can be converted by this value.
  • a drug containing the strain of the novel lactic acid bacterium according to the present invention preferably Lactobacillus paracasei MCC1375, and other drugs such as IL-12 production promoter, NK cell activation Agents, antiviral agents and the like may be used in combination.
  • the administration time of the pharmaceutical of the present invention is not particularly limited, and can be appropriately selected according to the treatment method for the target disease. It may be administered prophylactically or used for maintenance therapy.
  • the dosage form is preferably determined according to the dosage form, the patient's age, sex, other conditions, the degree of symptoms of the patient, and the like.
  • the pharmaceutical of the present invention can be administered once or a plurality of times a day, or can be administered once every several days or weeks.
  • composition for promoting IL-12 production The medicament of the present invention can be preferably used as a composition for promoting IL-12 production.
  • the composition for promoting IL-12 production according to the present invention contains the strain of the novel lactic acid bacterium according to the present invention, preferably Lactobacillus paracasei MCC1375 as an active ingredient, and remarkably produces in vivo IL-12. Can be promoted. Increased IL-12 activates cellular immunity. Therefore, since the composition for promoting IL-12 production of the present invention can enhance cellular immunity, allergic symptoms such as food allergy, bronchial asthma, urticaria, rhinitis, hay fever, anaphylactic shock, etc.
  • the IL-12 production promoting composition of the present invention can be used as a composition for inducing IL-12 production, and more specifically, an antitumor agent, a prophylactic or therapeutic agent for opportunistic infections, an allergy It can be widely used as a disease preventive or therapeutic agent.
  • the content of Lactobacillus paracasei MCC1375 strain in the composition for promoting IL-12 production of the present invention is appropriately set depending on the dosage form, usage, patient age, sex, disease type, disease severity, and other conditions. However, it is usually preferably in the range of 1 ⁇ 10 6 to 1 ⁇ 10 12 pieces / g, and more preferably in the range of 1 ⁇ 10 7 to 1 ⁇ 10 11 pieces / g.
  • the IL-12 production promoting composition of the present application may be used in combination with other IL-12 production promoting compositions.
  • the administration time of the composition for promoting production of IL-12 of the present invention is not particularly limited, and the administration time can be appropriately selected according to the treatment method for the target disease. It may be administered prophylactically or used for maintenance therapy.
  • the dosage form is preferably determined according to the dosage form, the patient's age, sex, other conditions, the degree of symptoms of the patient, and the like.
  • the pharmaceutical of the present invention can be administered once or a plurality of times a day, or can be administered once every several days or weeks.
  • the IL-12 production promoting effect can be confirmed by measuring the amount of IL-12 production.
  • IL-12 production is preferably measured by ELISA.
  • the medicament of the present invention can be used as a composition for activating NK cells (natural killer cells).
  • NK cells are a group of cells having cytotoxic activity against various tumor cells, virus-infected cells, and cells with different major histocompatibility antigens, and are mainly activated or suppressed by receptors that recognize self and non-self.
  • the composition for NK cell activation of the present invention contains the strain of the novel lactic acid bacterium according to the present invention, preferably Lactobacillus paracasei MCC1375 as an active ingredient, and remarkably activates NK cells in vivo. Therefore, it can be used for the prevention and treatment of diseases that can be prevented by the proliferation of NK cells.
  • NK cells Diseases that can be prevented by proliferation of NK cells are specifically allergic symptoms, specifically food allergies, bronchial asthma, urticaria, rhinitis, hay fever, anaphylactic shock, etc., as well as resistance to infectious diseases Improvement, prevention of cancer, prevention of progression, and the like.
  • the composition for activating NK cells of the present invention can be widely used as an antitumor agent, a prophylactic or therapeutic agent for opportunistic infections, an allergic disease preventive agent, or a therapeutic agent.
  • the NK cell activation effect can be confirmed, for example, by measuring the proportion of NK cells in mouse spleen cells.
  • the ratio of NK cells is preferably measured by flow cytometry.
  • the content of the Lactobacillus paracasei MCC1375 strain in the composition for activating NK cells of the present invention is appropriately set depending on the dosage form, usage, patient age, sex, disease type, disease severity, and other conditions. However, it is usually preferably in the range of 1 ⁇ 10 6 to 1 ⁇ 10 12 pieces / g, and more preferably in the range of 1 ⁇ 10 7 to 1 ⁇ 10 11 pieces / g. Moreover, as long as the effect of this invention is not impaired, you may use together the composition for NK cell activation of this application, the composition for other NK cell activation, etc.
  • the administration time of the composition for activating NK cells of the present invention is not particularly limited, and the administration time can be appropriately selected according to the treatment method for the target disease. It may be administered prophylactically or used for maintenance therapy.
  • the dosage form is preferably determined according to the dosage form, the patient's age, sex, other conditions, the degree of symptoms of the patient, and the like.
  • the pharmaceutical of the present invention can be administered once or a plurality of times a day, or can be administered once every several days or weeks.
  • the medicament of the present invention can be used as an antiviral composition, particularly as an anti-influenza virus composition.
  • the composition for anti-influenza virus of the present invention can be used for prevention or treatment of diseases caused by influenza virus.
  • the anti-influenza virus composition of the present invention contains the novel lactic acid bacterium strain according to the present invention, preferably the Lactobacillus paracasei MCC1375 strain as an active ingredient, and significantly reduces the number of influenza viruses in vivo. Can be made.
  • the anti-influenza virus agent of the present invention can remarkably suppress the proliferation of the number of influenza viruses in the living body, and can prevent and / or improve symptoms caused by influenza virus infection. Therefore, the anti-influenza virus composition of the present invention can be used for the prevention and treatment of infectious diseases caused by the proliferation of influenza virus.
  • the content of Lactobacillus paracasei MCC1375 strain in the antiviral composition of the present invention is appropriately set depending on the dosage form, usage, patient age, sex, disease type, disease severity, and other conditions. Usually, it is preferably in the range of 1 ⁇ 10 6 to 1 ⁇ 10 12 pieces / g, and more preferably in the range of 1 ⁇ 10 7 to 1 ⁇ 10 11 pieces / g. Moreover, unless the effect of this invention is impaired, you may use together the composition for anti-influenza viruses of this application, the composition for other anti-influenza viruses, etc.
  • the administration time of the anti-influenza virus composition of the present invention is not particularly limited, and the administration time can be appropriately selected according to the treatment method for the target disease.
  • the dosage form is preferably determined according to the dosage form, the patient's age, sex, other conditions, the degree of symptoms of the patient, and the like.
  • the pharmaceutical of the present invention can be administered once or a plurality of times a day, or can be administered once every several days or weeks.
  • the anti-influenza virus effect is measured by measuring the infection score obtained by observing the state of the mouse and scoring the infection model in which the influenza virus was inoculated from the nasal cavity after administering the antiviral composition of the present invention to the mouse.
  • the weight loss rate after infection, the measurement of the virus concentration in the lungs of mice after infection, etc. can be comprehensively evaluated and judged. It is preferable to measure the virus concentration in the mouse lung by a plaque assay method using MDCK cells (canine kidney-derived cells).
  • the food / beverage product of the present invention is not particularly limited as long as it contains the strain of the novel lactic acid bacterium according to the present invention, preferably Lactobacillus paracasei MCC1375 strain, and food / beverage products include soft drinks, carbonated drinks, nutritional drinks, fruit juice drinks, And beverages such as lactic acid bacteria beverages (including concentrated concentrates and powders for preparation thereof); ice confectionery such as ice cream, sherbet, shaved ice; candy, chewing gum, candy, gum, chocolate, tablet confectionery, snack confectionery, biscuits, jelly Confectionery such as jam, cream and baked confectionery; processed milk, dairy drinks, fermented milk, drink yogurt, butter and other dairy products; bread; enteral nutrition, liquid food, infant milk, sports drink; other functions Examples include sex foods.
  • the food and drink may be a supplement, for example, a tablet-like supplement.
  • a supplement the Lactobacillus paracasei MCC1375 strain can be ingested without being influenced by other foods in terms of the daily meal amount and calorie intake.
  • the food and drink of the present invention can be produced by adding the strain of the novel lactic acid bacterium according to the present invention, preferably Lactobacillus paracasei MCC1375, to the raw material of the food and drink, except that the above strain is added, It can be produced in the same manner as ordinary food and drink.
  • the addition of the strain may be performed at any stage of the production process of the food or drink.
  • food-drinks may be manufactured through the fermentation process by the added strain.
  • a raw material for food or beverage a raw material used for a normal beverage or food can be used.
  • the manufactured food and drink can be taken orally.
  • the content of the Lactobacillus paracasei MCC1375 strain in the food and drink of the present invention is appropriately set according to the shape of the food and drink, the amount of intake, the age of the intaker, sex and other conditions, etc. Usually, it is preferably in the range of 1 ⁇ 10 6 to 1 ⁇ 10 12 pieces / g, and more preferably in the range of 1 ⁇ 10 7 to 1 ⁇ 10 11 pieces / g. Therefore, in the case of viable bacteria, it is usually preferably in the range of 1 ⁇ 10 6 to 1 ⁇ 10 12 CFU / g, more preferably in the range of 1 ⁇ 10 7 to 1 ⁇ 10 11 CFU / g. be able to.
  • the food / beverage products of the present invention can be used for various applications utilizing the IL-12 production promoting effect, the NK cell activation effect, and the antiviral effect.
  • the food / beverage products of the present invention can be sold as food / beverage products that display IL-12 production promotion, NK cell activation, and antiviral uses. That is, the food and drink of the present invention includes “for IL-12 production promotion”, “for NK cell activation”, “for antiviral”, “for anti-influenza virus”, “for antiallergy”, “infectious disease” “Prevention”, “immunity activation”, “immunostimulation”, and the like can be displayed. In addition to this, any language that expresses the effects and uses of the above-mentioned promotion of IL-12 production, activation of NK cells, anti-virus, etc. can be used for display.
  • the “display” means all acts for informing the consumer of the use, and if it is a display that can recall and analogize the use, the purpose of the display, the content of the display, the display Regardless of the object and medium to be used, all of them correspond to the “display” of the present invention. However, it is preferable to display in such an expression that the consumer can directly recognize the application.
  • the act of describing the above-mentioned use in the product or product packaging relating to the food or drink of the present invention the product or product packaging describing the above-mentioned use is transferred, and displayed for delivery, transfer or delivery And display or distribute the above uses in the acts of importing, advertising about products, price lists or transaction documents, or displaying or distributing the above uses in the information containing them, Or, it is possible to exemplify the act of providing the above uses in the information containing the contents and providing them by electromagnetic methods (Internet etc.), especially advertising materials at sales sites such as packaging, containers, catalogs, pamphlets, POP, etc. Display on documents is preferable.
  • the display is preferably a display permitted by the government or the like (for example, a display which is approved based on various systems determined by the government and is performed in a mode based on such approval).
  • indications such as health foods, functional foods, enteral nutrition foods, special purpose foods, functional nutrition foods, quasi-drugs, and other indications approved by the Ministry of Health, Labor and Welfare, such as specific Examples of indications approved by health foods and similar systems. Examples of the latter include a display as a food for specified health use, a display as a food for specific specified health use, a display that affects the structure and function of the body, a display for reducing disease risk, and the like.
  • the strain of the novel lactic acid bacterium according to the present invention preferably Lactobacillus paracasei MCC1375 strain
  • the Lactobacillus paracasei MCC1375 strain has the property that the survival at low pH is remarkably high. Due to this property, a lactic acid bacteria beverage using this strain can be adjusted to a pH as low as previously unattainable.
  • the pH of the lactic acid bacteria beverage of the present invention can be used without any particular limitation, but in order to make full use of the characteristics of Lactobacillus paracasei MCC1375 strain, the pH is preferably 7 or less, more preferably 6 or less, and pH 5 0.5 or lower is more preferable, pH 5 or lower is further preferable, pH 4 or lower is further preferable, pH 3.5 or lower is further preferable, and pH 3.0 or lower is further preferable.
  • the lower limit of the pH is not particularly limited, and can be, for example, pH 1.0 or more, pH 1.5 or more, pH 2.0 or more, pH 2.5 or more, pH 3.0 or more.
  • Beverages to which lactic acid bacteria are added can be used for mandarin oranges, oranges, lemons, apples, grapes, pears, grapefruits, pomegranates, figs and other fruit drinks, soft drinks, milk drinks such as milk and cocoa, coffee, etc. .
  • the lactic acid bacteria beverage of the present invention can maintain a viable lactic acid bacteria count of about 10 6 cfu / ml even after storage at 10 ° C. for 1 month, for example.
  • This storage condition is that of L. cerevisiae, which is a closely related strain.
  • feed of the present invention examples include pet food, livestock feed, and fish feed.
  • the feed of the present invention is mixed with Lactobacillus paracasei MCC1375 in general feed such as cereals, potatoes, potatoes, fish meal, bone meal, fats and oils, skim milk powder, whey, mineral feed, yeasts, etc. Can be manufactured.
  • a feed may be manufactured through the fermentation process by the added Lactobacillus paracasei MCC1375 strain
  • the produced feed can be orally administered to general mammals, livestock, fish farms, pets and the like.
  • the content of the Lactobacillus paracasei MCC1375 strain in the feed of the present invention is appropriately set depending on the type of the target animal, the age, sex, intake, and other conditions of the target animal, but usually 1 ⁇ 10 6 to 1 It is preferably in the range of ⁇ 10 12 pieces / g, more preferably in the range of 1 ⁇ 10 7 to 1 ⁇ 10 11 pieces / g.
  • the novel lactic acid bacteria strain according to the present invention preferably Lactobacillus paracasei MCC1375 strain
  • fermented milk can be produced by adding the fermented milk production starter to the raw material of the fermented milk and fermenting it.
  • a raw material of fermented milk a well-known raw material can be used without a restriction
  • the produced fermented milk contains the strain of the novel lactic acid bacterium according to the present invention, preferably the Lactobacillus paracasei MCC1375 strain, it has an advantageous effect as described above compared to the conventional lactic acid bacterium. It is.
  • the strain of the novel lactic acid bacteria according to the present invention preferably the Lactobacillus paracasei MCC1375 strain
  • this fermented milk contains the strain of the novel lactic acid bacterium according to the present invention, preferably the Lactobacillus paracasei MCC1375 strain. It has such an advantageous action.
  • the present invention also resides in a mutant strain of Lactobacillus paracasei MCC1375 strain having low pH survival.
  • a mutant strain of MCC1375 strain a mutant strain obtained by mutating MCC1375 strain can be prepared and used.
  • known mutation means such as UV can be used.
  • such a mutant strain has, for example, a base sequence identity to the base sequence of the 16S rRNA gene of MCC1375 strain (length 1476 from base 11 to base 1486). , Preferably 99.86% or more, more preferably 99.93% or more, more preferably 100%.
  • the mutant strain of MCC1375 strain is not limited to those having such nucleotide sequence identity.
  • acidic survival can be confirmed against the mutant strain of MCC1375 strain.
  • the survival rate after storage for 4 weeks at 10 ° C. at pH 3.0 is 90% or more, or the survival rate after storage for 6 weeks at 10 ° C. at pH 3.0, for example. Is preferably 40% or more.
  • These storage conditions are determined by L. cerevisiae, a strain that appears to be closely related.
  • Rhamnosus ATCC 53103 strain, L. Paracasei ATCC 25302 T strain and L. All of the casei ATCC 393 T strains have a survival rate of less than 0.1% or below the detection limit.
  • the mutant strain of MCC1375 strain is not limited to those having these survival conditions.
  • the mutant strain of MCC1375 strain can be contained as an active ingredient of the medicament of the present invention, like the MCC1375 strain of the present invention, and can be contained as an active ingredient of the food and drink of the present invention. It can be contained as an active ingredient.
  • a medicament containing a mutant of MCC1375 strain it is preferably used as a composition for promoting IL-12 production, preferably used as a composition for NK cell activation, and as a composition for anti-influenza virus. It is preferable to use it.
  • the mutant strain of MCC1375 strain is preferably used as an active ingredient of a lactic acid bacteria beverage.
  • IL-12 production inducing ability was evaluated using mouse spleen cells in a group of lactic acid bacteria including MCC1375 strain.
  • the lactic acid bacteria group includes Lactobacillus rhamnosus ATCC 53103 strain (GG strain), Lactobacillus reuteri JCM1112 strain, Enterococcus faecalis JCM5803 strain, Bifidobacterium longum ATCC 15707 strain, Lactobacillus ⁇ Gasseri JCM5343 strain is included.
  • Spleen cells were collected from the collected spleen and treated with erythrocyte lysate (0.144M ammonium chloride, 17 mM trisaminomethane, pH 7.65) for 3 minutes to prepare a erythrocyte-removed product.
  • the prepared spleen cells were suspended in RPMI1640 (SIGMA) in a medium containing 10% FCS (Gibco), 100 IU / ml penicillin, 0.1 mg / ml streptomycin to 2 ⁇ 10 6 cells / ml.
  • a lactic acid bacterium dead cell sample was added to a final concentration of 1 ⁇ g / ml (3.75 ⁇ 10 6 cells / ml), and a 96-well microplate (manufactured by FALCON) at 37 ° C. with 5% CO Cultured in the presence of 2 . Two days later, the culture supernatant was collected, and the concentration of IL-12p70 in the culture supernatant was measured using DuoSet (DY419) manufactured by R & D systems. The test was performed three times, and the average value is shown in Table 2.
  • Table 2 shows the average value of IL-12 production by each lactic acid strain.
  • the IL-12 production amount was 254 pg / ml, indicating the highest IL-12 production inducing ability among the lactic acid bacteria tested.
  • the amount of IL-12 produced by the Lactobacillus rhamnosus ATCC 53103 strain was 87 pg / ml. Therefore, in the amount of IL-12 produced, the Lactobacillus paracasei MCC1375 strain of the present invention was 2.9 times the Lactobacillus rhamnosus ATCC53103 strain.
  • the IL-12 production amount of Lactobacillus reuteri JCM1112 strain is 48 pg / ml
  • the IL-12 production amount of Enterococcus faecalis JCM5803 strain is 25 pg / ml
  • the IL-12 production amount of Bifidobacterium longum ATCC15707 T strain was 14 pg / ml
  • the amount of IL-12 produced by Lactobacillus gasseri strain JCM5343 was 0.7 pg / ml.
  • the Lactobacillus paracasei MCC1375 strain had a remarkable effect of promoting IL-12 production as compared with the conventional strain of lactic acid bacteria.
  • Test Example 2 Evaluation of IL-12 production inducing ability using human-derived peripheral blood mononuclear cells (PBMC) [Test method] The ability to induce IL-12 production of Lactobacillus paracasei MCC1375 strain was verified using human-derived PBMC. A dead cell of Lactobacillus paracasei MCC1375 strain was prepared in the same manner as in Test Example 1. A healthy person's PBMC (obtained from Lonza Walkersville Inc) was added to X-VIVO (Lonza) with 10% FCS (Gibco), 100 IU / ml penicillin, 0.1 mg / ml streptomycin.
  • PBMC peripheral blood mononuclear cells
  • the vertical axis indicates the amount of IL-12 production
  • the horizontal axis indicates the amount of MCC1375 strain added.
  • concentration of MCC1375 strain dead cells was 0.1 ⁇ g / ml
  • IL-12 production was 1139 pg / ml.
  • concentration was 0.4 ⁇ g / ml
  • IL-12 production was 1476 pg / ml.
  • concentration was 1.1 ⁇ g / ml
  • IL-12 production was 1595 pg / ml.
  • the concentration was 3.3 ⁇ g / ml
  • IL-12 production was 2020 pg / ml.
  • IL-12 production was 2104 pg / ml.
  • dead cells of MCC1375 strain induced IL-12 production from human-derived PBMC in a concentration-dependent manner.
  • the IL-12 production-inducing action of the MCC1375 strain of the present invention was found to be effective against human immunocompetent cells.
  • the prepared AIN93-G diet (MCC1375 group) containing 0.01% dead cells of MCC1375 strain or a diet containing no cells (control group) was administered to 8-week-old male BALB / c mice (SLC) for 10 days. did.
  • mice mice were prepared, stained with fluorescently labeled anti-mouse CD3 antibody and anti-mouse DX5 antibody, CD3 negative DX5 positive cells were used as NK cells, and the ratio of NK cells in spleen cells was determined by flow cytometry (model). Name: FACSCanto, manufactured by Becton Dickinson). The test was performed 8 times, and the average value was obtained.
  • the evaluation criteria were 0 for normal, 1 for mild infection, 2 for moderate infection, 3 for severe infection and 4 for death.
  • the total of the numerical values of each item was divided by the number of items (4) to obtain a score for each mouse.
  • the body weight before infection and 6 days after infection was measured, and the weight loss rate 6 days after infection was measured.
  • 6 days after the infection the lungs were removed and the virus concentration in the lungs was measured by a plaque assay method using MDCK cells (canine kidney-derived cells).
  • FIG. 3A is a graph showing changes in symptom scores.
  • the horizontal axis represents the number of days after infection, and the vertical axis represents the symptom score.
  • FIG. 3B is a graph showing the weight loss rate.
  • the vertical axis is the weight loss rate compared to the weight before infection.
  • FIG. 3 (c) is a graph showing the virus concentration in the lungs of mice.
  • the t-test was used for the significant difference test of (a) to (c) in FIG. * In the figure indicates a statistically significant difference between the two groups. Moreover, + in a figure shows the statistical tendency between both groups. In the figure, control indicates a control group.
  • FIG. 3 (a) shows changes in symptom scores 1 to 6 days after infection.
  • the first day after infection was 0.00
  • the second day was 0.00
  • the third day was 0.08
  • the fourth day was 0.08
  • the fifth day was 0.28
  • the sixth day was 0.48.
  • the first day after infection was 0.03, the second day was 0.20
  • the third day was 0.48
  • the fourth day was 0.68
  • the fifth day was 1.00
  • the sixth day The eyes were 1.35.
  • the symptom score of the 2, 3, 4, and 6th day of the MCC1375 group the rise suppression of the symptom score was significantly seen compared with the control group.
  • the symptom score of the 5th day of the MCC1375 group showed the tendency for suppression of the symptom compared with the control group.
  • (B) in FIG. 3 shows the weight loss rate after infection.
  • the MCC1375 group was 4.8%, whereas the control group was 13.2%, and the MCC1375 group was found to significantly suppress the rate of weight loss after infection.
  • FIG. 3 (c) shows the virus concentration in the mouse lung.
  • the MCC1375 group is 1.21 ⁇ 10 6 pfu / g, whereas the control group is 0.57 ⁇ 10 6 pfu / g, and it is clear that the MCC1375 group significantly suppresses the virus concentration after infection. became.
  • Test method The culture of Lactobacillus paracasei MCC1375 strain, Lactobacillus rhamnolaus ATCC53103 strain, Lactobacillus paracasei ATCC25302 T strain, Lactobacillus casei ATCC393 T strain was added to 1000 ml of sterilized peach juice (pH 3.0). Four kinds of test solutions were prepared by adding about 10 7 cfu / ml. Next, 100 ml of each test solution was dispensed into a plastic container and stored at 10 ° C. or lower for 6 weeks. The number of lactic acid bacteria was measured immediately after preparation, 2 weeks after storage, 4 weeks and 6 weeks, and the survival rate. Asked.
  • the number of lactic acid bacteria was measured on a BCP-added plate count agar medium (manufactured by Eiken).
  • the survival rate is a numerical value indicating the percentage of the number of lactic acid bacteria after the storage period based on the number of lactic acid bacteria immediately after preparation of the test solution. The results are shown in Table 3.
  • Lactobacillus paracasei MCC1375 strains had survival rates of 102%, 93% and 41% after 2 weeks, 4 weeks and 6 weeks, respectively.
  • the remaining three lactic acid bacteria had a survival rate of almost 0% after 2 weeks, and were not detected at all after 4 weeks or 6 weeks.
  • Nd in Table 3 indicates that it was below the detection limit. From these results, it was revealed that the lactic acid bacteria of the present invention have remarkable survival in a low pH environment as compared with the same and related strains.
  • Example 1 1000 mL of a medium containing 10% reduced skim milk powder, 1% glucose, and 0.1% yeast extract was sterilized at 90 ° C. for 30 minutes, inoculated with 30 mL of a seed culture of Lactobacillus paracasei MCC1375 strain, and cultured at 37 ° C. for 16 hours.
  • skim milk powder, whole milk powder, pectin, and sucrose raw materials were mixed and dissolved, 0.5% milk fat, 8.0% non-fat milk solids, 5.0% sucrose, 50 L of base consisting of 0.2% pectin was sterilized at 90 ° C. for 10 minutes and cooled to 40 ° C.
  • the sterilized base was inoculated with 50 mL of the cultured Lactobacillus paracasei MCC1375 culture and cultured at 37 ° C. for 16 hours to obtain fermented milk.
  • the fermented milk was immediately stirred and cooled, and the cooled fermented milk was homogenized at a pressure of 15 MPa, filled in a 200 mL capacity glass container, and sealed to obtain 250 drink yogurts.
  • Example 2 Lactobacillus paracasei pre-cultured at 37 ° C. for 16 hours in a medium comprising 50 g of meat extract, 100 g of yeast extract, 100 g of peptone, 200 g of glucose, 50 g of K 2 HPO 4 , 10 g of KH 2 PO 4 , 4 g of cystine and 9.5 L of water.
  • 500 mL of seed culture of MCC1375 strain was inoculated into 10 L of medium having the same composition as the above medium and cultured at 37 ° C. for 16 hours. Further, 200 L of the medium having the same composition as the medium was inoculated with the whole culture solution (10.5 L) and cultured at 37 ° C. for 16 hours.
  • the cells were collected by centrifugation (15,000 rpm) using a sharpless centrifuge, resuspended in the same amount of physiological saline as the medium, and centrifuged again to collect the cells.
  • the collected cells were suspended in 20 L of a solution comprising 10% skim milk powder, 1% sucrose, and 1% sodium glutamate, lyophilized according to a conventional method, and triturated with the same amount of starch. About 5.0 kg of powder containing 3.75 ⁇ 10 12 CFU / g Lactobacillus paracasei MCC1375 strain was obtained.
  • Example 3 To 14 kg of dry-sterilized starch and 6 kg of lactose, 20 g of the powder containing Lactobacillus paracasei MCC1375 strain obtained in Example 2 was added and mixed uniformly to obtain 3.75 ⁇ 10 9 CFU / g Lactobacillus paracasei MCC1375. About 20 kg of a composition for inducing IL-12 production including the strain was obtained.
  • Example 4 To 7 kg of dry sterilized starch and 3.5 kg of lactose, 11 g of the powder containing Lactobacillus paracasei MCC1375 strain obtained in Example 2 was added and mixed uniformly, and 3.92 ⁇ 10 9 CFU / g of Lactobacillus. About 10 kg of a composition for NK cell activation containing Paracasei MCC1375 strain was obtained.
  • Example 5 To 10 kg of dry sterilized starch and 4.3 kg of lactose, 14 g of powder containing Lactobacillus paracasei MCC1375 strain obtained in Example 2 was added and mixed uniformly, and 3.67 ⁇ 10 9 CFU / g of Lactobacillus. About 14 kg of an anti-influenza virus composition containing Paracasei MCC1375 strain was obtained.
  • Example 6 14 kg starch, skim milk powder 13.5 kg, vegetable oil and fat 30 kg, soybean meal 13 kg, wheat flour 11 kg, vitamin mixture 9 kg, mineral mixture 2 kg, cellulose 3 kg, and Lactobacillus paracasei MCC1375 strain obtained in Example 2
  • the powder composition containing 2.5 kg of was added and mixed uniformly to obtain about 98 kg of a feed composition containing 9.57 ⁇ 10 10 CFU / g Lactobacillus paracasei MCC1375 strain.
  • the novel lactic acid bacteria of the present invention particularly the Lactobacillus paracasei MCC1375 strain, has high survival under acidic conditions, and has high IL-12 production-inducing ability even in dead cells.
  • pharmaceuticals for these uses especially oral preparations, functional foods and drinks for these uses, especially acidic lactic acid bacteria beverages, etc. It can be widely used.

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Abstract

L'invention concerne une nouvelle bactérie lactique ayant une viabilité élevée en conditions acides et un produit pharmaceutique, un aliment ou une boisson et un aliment pour animaux contenant tous la nouvelle bactérie lactique obtenue avec la souche Lactobacillus paracasei MCC 1375, et un produit pharmaceutique, un aliment ou une boisson et un aliment pour animaux contenant tous la souche.
PCT/JP2012/058690 2011-03-31 2012-03-30 Nouvelle bactérie lactique et produit pharmaceutique, aliment ou boisson et aliment pour animaux contenant tous la nouvelle bactérie lactique Ceased WO2012133827A1 (fr)

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CN103070287A (zh) * 2013-02-26 2013-05-01 湖南省微生物研究所 副干酪乳杆菌发酵饲料及其制备方法、发酵设备和用途
WO2015004949A1 (fr) 2013-07-12 2015-01-15 森永乳業株式会社 Nouveau lactobacillus et nouveau médicament, produit alimentaire, boisson et aliment pour animaux contenant un lactobacillus
JP2015092841A (ja) * 2013-11-11 2015-05-18 キッコーマン株式会社 経口免疫寛容増強物質のスクリーニング方法および経口免疫寛容増強組成物
KR101791850B1 (ko) * 2015-06-29 2017-11-01 (주)진바이오텍 반추가축용 완전배합사료 및 사일리지 발효 촉진제
CN107404890A (zh) * 2015-02-17 2017-11-28 株式会社益力多本社 发酵乳食品的制造方法
KR20190104308A (ko) 2017-06-09 2019-09-09 아사히 코우산 가부시키가이샤 유산균의 균체외 다당 및 그 용도
KR20190111890A (ko) 2017-06-09 2019-10-02 아사히 코우산 가부시키가이샤 신규 유산균 및 그 용도
EP3714701A4 (fr) * 2018-04-25 2021-02-17 Sone Farm Co., Ltd. Composition pour allergie de type iv
JP2021090408A (ja) * 2019-11-28 2021-06-17 雪印種苗株式会社 新規乳酸菌及びサイレージ調製用乳酸菌製剤、サイレージ調製方法
US20230080134A1 (en) * 2020-01-16 2023-03-16 National University Of Singapore A coffee-based beverage
US11617771B2 (en) 2016-12-15 2023-04-04 The Regents Of The University Of California Oral composition comprising lactic acid bacteria for regulating immune responses and methods related thereto
WO2023185569A1 (fr) * 2022-04-01 2023-10-05 江南大学 Lactobacillus pentosus pouvant soulager les caractéristiques pathologiques des souris infectées par des virus grippaux et son utilisation
WO2023218898A1 (fr) 2022-05-13 2023-11-16 三菱瓦斯化学株式会社 Nouvelles bactéries lactiques, et composition, article du type aliment/boisson et article pharmaceutique contenant des bactéries lactiques
WO2024004139A1 (fr) * 2022-06-30 2024-01-04 森永乳業株式会社 Lait fermenté et procédé de production de lait fermenté

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KR20190111890A (ko) 2017-06-09 2019-10-02 아사히 코우산 가부시키가이샤 신규 유산균 및 그 용도
US11447740B2 (en) 2017-06-09 2022-09-20 Sone Farm Co., Ltd. Lactic acid bacterium and use thereof
EP3714701A4 (fr) * 2018-04-25 2021-02-17 Sone Farm Co., Ltd. Composition pour allergie de type iv
JP2021090408A (ja) * 2019-11-28 2021-06-17 雪印種苗株式会社 新規乳酸菌及びサイレージ調製用乳酸菌製剤、サイレージ調製方法
JP7609352B2 (ja) 2019-11-28 2025-01-07 雪印種苗株式会社 新規乳酸菌及びサイレージ調製用乳酸菌製剤、サイレージ調製方法
US20230080134A1 (en) * 2020-01-16 2023-03-16 National University Of Singapore A coffee-based beverage
WO2023185569A1 (fr) * 2022-04-01 2023-10-05 江南大学 Lactobacillus pentosus pouvant soulager les caractéristiques pathologiques des souris infectées par des virus grippaux et son utilisation
WO2023218898A1 (fr) 2022-05-13 2023-11-16 三菱瓦斯化学株式会社 Nouvelles bactéries lactiques, et composition, article du type aliment/boisson et article pharmaceutique contenant des bactéries lactiques
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WO2024004139A1 (fr) * 2022-06-30 2024-01-04 森永乳業株式会社 Lait fermenté et procédé de production de lait fermenté

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