WO2012005240A1 - 腸内腐敗物質の低減作用を有するビフィズス菌 - Google Patents

腸内腐敗物質の低減作用を有するビフィズス菌 Download PDF

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WO2012005240A1
WO2012005240A1 PCT/JP2011/065350 JP2011065350W WO2012005240A1 WO 2012005240 A1 WO2012005240 A1 WO 2012005240A1 JP 2011065350 W JP2011065350 W JP 2011065350W WO 2012005240 A1 WO2012005240 A1 WO 2012005240A1
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concentration
bifidobacteria
reducing
intestinal
microorganisms
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公子 天藤
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株式会社明治
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Priority to CN201180033393.0A priority Critical patent/CN102959075B/zh
Priority to JP2012523872A priority patent/JP5837879B2/ja
Publication of WO2012005240A1 publication Critical patent/WO2012005240A1/ja
Priority to HK13110266.1A priority patent/HK1183058A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
    • 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; MAKING 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
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/127—Fermented milk preparations; Treatment using microorganisms or enzymes using microorganisms of the genus lactobacteriaceae and other microorganisms or enzymes, e.g. kefir, koumiss
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • 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
    • 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
    • A23V2400/51—Bifidobacterium
    • A23V2400/519—Breve
    • A—HUMAN NECESSITIES
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    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K2035/11—Medicinal preparations comprising living procariotic cells
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    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales

Definitions

  • the present invention relates to a method for improving the state of enteric bacteria. More specifically, the present invention relates to selection of useful microorganisms that reduce indole compounds that cause rot odor caused by intestinal bacteria, and the selected microorganisms.
  • Non-patent Document 1 An increasing number of people complain of symptoms such as repeated constipation and diarrhea, stomach up, and outgassing due to disordered eating habits, irregular lifestyles, and stress. These symptoms are thought to be due to the influence of the intestinal environment, in other words, the prevalence of spoilage bacteria in the intestinal flora.
  • the intestinal microflora produces spoiled odor components such as indole and its derivatives from tryptophan under anaerobic conditions.
  • Several studies have been conducted on the relationship between such intestinal flora and the production of spoilage products (Non-patent Document 1).
  • Indole is also considered to be produced from tryptophan by intestinal spoilage bacteria, absorbed from the intestine, metabolized to indoxyl in the liver, and further combined with sulfuric acid to become indoxyl sulfate. In healthy humans, indoxyl sulfate is excreted in the urine, but it is considered to cause complications such as uremia in dialysis patients and the like (Non-patent Document 2).
  • Patent Document 1 uses a bifidobacterum / thermophilum having an indole-reducing ability.
  • Patent Document 2 describes that an extract or finely ground product of a Salacia plant is used in combination with lactic acid bacteria and / or bifidobacteria to improve the intestinal environment.
  • Patent Document 3 describes that a composition containing propionic acid bacteria promotes the growth of bifidobacteria in the intestine and prevents the release of malodorous gases. It has also been reported that inulin and oligosaccharides are useful for improving the intestinal bacterial flora (Non-patent Document 3).
  • the present invention has an object to effectively reduce enteric spoilage substances by effectively using highly safe and useful microorganisms.
  • the above-mentioned spoilage substances are mainly produced in the large intestine, and examples of microorganisms (bacteria species) that are dominant in the large intestine include lactic acid bacteria and bifidobacteria (genus Bifidobacterium).
  • This bifidobacteria has been used for food since ancient times as a microorganism that exhibits useful functions in vivo, and has a track record of eating experience. Therefore, it is a first object of the present invention to select microorganisms (strains) that can effectively reduce spoilage substances from bifidobacteria predominate in the human body (intestines).
  • the present invention provides a second in vitro and in vivo system suitable as a verification or search system for the action effect of a substance or microorganism that reduces spoilage substances generated in vivo (in the intestine). Let it be an issue.
  • the present inventor completed the present invention by isolating strains that effectively reduce intestinal spoilage substances from lactic acid bacteria and bifidobacteria as highly safe and useful microorganisms based on the screening method of the present invention. It was.
  • the inventor of the present application uses a buffer solution to proliferate bacterial cells when screening in vitro as a verification system for the action effect of a substance or microorganism that reduces spoilage substances generated in the living body (intestine).
  • the inventor of the present application is characterized in that the reaction solution is set (designed) to the amount of glucose that is the minimum energy necessary for the reduction of spoilage substances under conditions where lactic acid bacteria and bifidobacteria hardly grow.
  • An in-vitro selection method and / or evaluation method for microorganisms (such as lactic acid bacteria and bifidobacteria) that reduce spoilage substances produced by intestinal bacteria was established.
  • the inventor of the present application uses a mouse as a verification system for the action effect of a substance or a microorganism that reduces spoilage substances generated in vivo (in the intestine), from the serum, using a mouse.
  • a mouse was studied to measure indoxyl sulfate.
  • the present inventor added fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) and tryptophan (L-Tryptophan) to the diet (powder diet), raised the mouse, and indoxyl sulfate in the serum.
  • a method for selecting and / or evaluating microorganisms such as lactic acid bacteria and bifidobacteria
  • concentration such as lactic acid bacteria and bifidobacteria
  • strains that can effectively reduce spoilage substances
  • the present inventor first selects bifidos that are generally dominant in the human body (intestines) as highly safe and useful microorganisms. Focusing on the fungus, a total of 196 strains, 32 strains of Bifidobacterium ifbreve, 92 strains of Bifidobacterium longum, 72 strains of Bifidobacterium adolescenti, were screened and evaluated by in vitro, and 9 strains were preliminarily selected.
  • the present invention includes medicines and foods containing Bifidobacterium as an active ingredient, which has a strong action of reducing the indole selected above and shows a reduction action of indoxyl sulfate in serum.
  • Bifidobacterium breve (B. breve) of the present invention is a human-derived strain and has an excellent effect of significantly reducing indole and indoxyl sulfate in serum in a system in which the strain itself does not grow.
  • B. breve which has long been edible, has high safety, and the bifidobacteria OLB6129 of the present invention can be widely applied and applied in the food and pharmaceutical fields.
  • Bifidobacterium breve live bacteria
  • Bifidobacterium longum live bacteria
  • B. breve OLB6129 live bacteria concentration on the serum indoxyl sulfate concentration after oral administration of B. breve OLB6129 (live bacteria) to mice Number of colonies of B.Bbreve OLB6129 in feces (Fecal) and caecal contents (cecal) detected on TOS propionate agar medium
  • microorganisms that are dominant in the large intestine include Lactobacillus and Bifidobacterium (Bifidobacterium spp.). Bifidobacteria have been used in food since ancient times as microorganisms that exhibit useful functions in vivo. In addition, bifidobacteria are said to have an intestinal regulating action, and are also used for intestinal preparations, etc., which also helps improve the intestinal flora, through the improvement of the intestinal environment, diarrhea suppression, prevention of rough skin, hay fever improvement, It is also said to be effective for immunity Taoism.
  • the present inventor first uses a buffer solution to reproduce conditions under which microorganisms are difficult to grow, The evaluation method of the reduction effect (reduction ability) was examined. By adopting such conditions, it is possible to select excellent microorganisms under conditions closer to the intestinal environment, in which spoilage substances can be removed even if the microorganisms do not grow. For example, the components and concentration of the reaction solution can be determined under conditions in which the target microorganism hardly grows and under conditions that set the minimum energy necessary for reducing spoilage substances.
  • the amount of the medium component serving as an energy source can lower the concentration of glucose, lactose, fructose, etc., compared to the normal culture conditions of the target microorganism, and remove intestinal spoilage substances.
  • a degree of 0.3 to 0.7 (w / v)% can be applied.
  • fructooligosaccharide (FOS) was added to the diet.
  • the reduction effect of indoxyl sulfate in the solution was confirmed.
  • the mouse generally used in animal experiments is a young healthy individual, the amount of spoilage substances in the living body is suppressed to a very small amount and often falls below the detection limit. Therefore, in the present invention, in an animal experiment using a mouse, tryptophan (L-Tryptophan), which is a precursor of indole in vivo, is added to the diet (powder), and the baseline of indole generated in vivo is determined. Attempts to increase showed a significant increase in the indole baseline. In other words, the concentration of indoxyl sulfate in serum, which is an index (marker) of spoilage substances, can be evaluated stably and reliably. And the reduction
  • fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) and tryptophan (L-Tryptophan) are added to a diet (powder) at a predetermined concentration, and a general mouse (for animal experiments) is added. It can be reared and the concentration of indoxyl sulfate in serum can be evaluated. At this time, the concentration of the total amount of fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) is 0.5 to 20 (w / v)%, preferably 0.5 to 15 (w / v)%, more preferably , 0.5 to 10 (w / v)%.
  • fructooligosaccharide (FOS) concentration is set to 0.5 (w / v)%, the viability of B. breve OLB6129 is significant as the number of viable bacteria in feces. Has been confirmed to improve.
  • the concentration of tryptophan is set to 1 to 4 (w / v)%, preferably 1.5 to 3.5 (w / v)%, and more preferably 2 to 3 (w / v)%.
  • microorganisms such as lactic acid bacteria and bifidobacteria
  • bifidobacteria microorganisms of the genus Bifidobacterium
  • microorganisms that reduce intestinal spoilage substances The inventor of the present application generally chooses microorganisms (strains) that can effectively reduce spoilage substances as microorganisms that reduce intestinal spoilage substances.
  • strains The study was conducted on lactic acid bacteria and bifidobacteria, particularly bifidobacteria, which are dominant in (1).
  • a bifidobacteria a total of 196 strains including 32 strains of B. breve, 92 strains of B. longum, and 72 strains of B. adolescentis were screened and evaluated in vitro. As a result, a total of 9 strains of 6 strains of B. breve and 3 strains of B. longum were selected.
  • the selected nine strains were subjected to animal experiments and evaluated in vivo. As a result, a strain that exhibits the effect of reducing indole in the intestine was selected.
  • the screened Bifidobacterium breve OLB6129 (B. breve OLB6129) is an independent administrative agency, National Institute of Advanced Industrial Science and Technology, Patent Biological Deposit Center (Contact: Postal Code 305-8566, Tsukuba 1-1-1, Higashi, Tsukuba, Japan Deposited on May 26, 2010 at Center Center No. 6), and this microorganism is deposited under the accession number as FERM BP-11257.
  • microorganisms that reduce intestinal spoilage 4-1 Food containing microorganisms that reduce intestinal spoilage substances
  • the microorganisms (such as lactic acid bacteria and bifidobacteria, preferably B. breve OLB6129) that reduce the intestinal spoilage substances of the present invention can be added to foods. That is, as the food of the present invention, any food to which microorganisms that reduce intestinal spoilage substances are added can be mentioned, and preferably fermented milk products or fermented milk drinks to which microorganisms that reduce intestinal spoilage substances are added. More preferably, a microorganism (B.
  • fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) can be mentioned. It is known that GOS can be used in the same way as FOS (http://www.nyusankin.or.jp/scientific/hosono_3.html).
  • the addition amount of fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) is 0.5 to 20 (w / v)%, preferably 0.5 to 15 (w / v)% as the total concentration. Preferably, it can be set to 0.5 to 10 (w / v)%.
  • the food containing a microorganism (Lactic acid bacteria, bifidobacteria, etc., preferably B. breve OLB6129) that reduces intestinal spoilage substances of the present invention is a health health for preventing or improving dialysis complications for renal dialysis patients. It can be applied as food (functional food).
  • the pharmaceutical product containing a microorganism that reduces the intestinal spoilage substance of the present invention is a reducing agent for intestinal spoilage substance or prevention of dialysis complications for renal dialysis patients. It can be applied as an agent or an improving agent. Furthermore, the pharmaceutical product of the present invention can be applied as a stomach tension improving agent.
  • the pharmaceutical product of the present invention can be made into appropriate dosage forms such as powders, granules, tablets, capsules, and liquids.
  • the pharmaceutical of the present invention may contain fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS).
  • the content of fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) is 0.5 to 20 (w / v)%, preferably 0.5 to 15 (w / v)% as the total concentration. Preferably, it can be set to 0.5 to 10 (w / v)%.
  • excipients include starch, lactose, sucrose, methylcellulose, carboxymethylcellulose, sodium alginate, calcium hydrogen phosphate, synthetic aluminum silicate, microcrystalline cellulose, polyvinylpyrrolidone (PVP), and hydroxypropyl starch (HPS).
  • binder include starch, microcrystalline cellulose, sodium carboxymethylcellulose, polyvinyl pyrrolidone (PVP), gum arabic powder, gelatin, glucose, sucrose, and water / ethanol solutions thereof.
  • disintegrant examples include starch, carboxymethyl cellulose, carboxymethyl cellulose calcium, microcrystalline cellulose, hydroxypropyl starch, and calcium phosphate.
  • lubricants for example, carnauba wax, light anhydrous silicic acid, synthetic aluminum silicate, natural aluminum silicate, synthetic magnesium silicate, hardened oil, hardened vegetable oil derivative (Sterotex HM), sesame oil, white beeswax, titanium oxide , Dry aluminum hydroxide / gel stearic acid, calcium stearate, magnesium stearate, talc, calcium hydrogen phosphate, and sodium lauryl sulfate.
  • the pharmaceutical product of the present invention is desirably administered orally, and bifidobacteria have established safety, so that any amount can be administered.
  • the dosage can be as much as 1 billion bifidobacteria per day.
  • the number can be from 500 to 500 billion, and preferably from 10 to 500 billion.
  • glucose is set to 0.7 (w / v)% or less, preferably 0.6 (w / v)% or less, and more preferably 0.55 (w / v)% or less.
  • glucose is set to, for example, 0.3 (w / v)% or more, preferably 0.4 (w / v)% or more, and more preferably 0.45 (w / v)% or more.
  • the composition of the reaction solution was determined for the other components.
  • the composition of the reaction solution should be 20 ⁇ g each of phenol, p-cresol, indole, skatole, 0.1 M Bis-Tris, 0.75 mM magnesium sulfate (MgSO 4 ), and 0.5 (w / v)% glucose.
  • PH is about 6.5.
  • Example 1 Selection of microorganisms capable of reducing spoilage substances "in vitro test" A total of 199 B. breve strains, 93 B. longum strains, and 72 B. adolescentis 72 strains were statically cultured, and two B. breve strains and one B. longum strain grew extremely. It was late. Therefore, these three strains were excluded from the experiment. Finally, a total of 196 strains (evaluation / selection) of 32 strains of B. breve, 92 strains of B. longum and 72 strains of B. adolescentis were selected. did.
  • this supernatant was extracted twice with diethyl ether, and the extract was made up to 5 ml, and the solution was subjected to gas chromatography (GC) to indole, phenol, p-cresol, The concentration of skatole was measured (detected).
  • GC gas chromatography
  • GC-2014 Shiadzu
  • TC-1 GL Sciences Inc.
  • ID 0.25mm
  • L 30mm
  • dF 0.25mm
  • column temperature 60 -170 °C (increased by 5 °C / min)
  • 170-250 °C increased by 20 °C / min
  • carrier gas nitrogen
  • flow rate 71.3 ml / min
  • injector temperature 240 °C
  • detector temperature 250 °C
  • injection volume 1 ⁇ l.
  • Table 1 32 strains of B. breve
  • Table 2 92 strains of B. longum
  • Table 3 72 strains of B. adolescentis
  • strains whose reference numbers begin with “JCM” are stored in the following storage organizations.
  • Example 2 Selection of microorganisms capable of reducing spoilage substances "in vivo test (animal experiment)" Nine strains selected in Example 1 above were screened (evaluated and selected) by animal experiments (in vivo tests).
  • the strain (live bacteria) to be administered to the mice was selected (screened) by an in vitro test. Specifically, 6 strains of B. breve (MEP22023004, OLB6129, MEP22023007, MEP22023012, MEP22023015, MEP22023016) and 3 strains of B. longum (MEP22023039, MEP22023061, MEP22023078) were selected. Then, an equal volume of physiological saline was used as a control group, and the administration group of a predetermined strain (live bacteria) was compared with the effect of reducing spoilage substances. The results are shown in FIG. 1 (6 strains of B. breve) and FIG. 2 (3 strains of B. longum).
  • mice Effect of presence or absence of FOS administered to living body on reduction effect of spoilage substances
  • SLC Balb / c mice
  • Table 5 the mice were divided into 4 groups based on body weight. Suspension of B. breve OLB6129 (viable bacteria) in water and physiological saline, and suspension of B. breve OLB6129 (viable bacteria) in saline and physiological saline with FOS added in 2 weeks Orally administered in the morning.

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PCT/JP2011/065350 2010-07-05 2011-07-05 腸内腐敗物質の低減作用を有するビフィズス菌 WO2012005240A1 (ja)

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Application Number Priority Date Filing Date Title
CN201180033393.0A CN102959075B (zh) 2010-07-05 2011-07-05 具有肠内腐败物质的减少作用的双歧杆菌
JP2012523872A JP5837879B2 (ja) 2010-07-05 2011-07-05 腸内腐敗物質の低減作用を有するビフィズス菌
HK13110266.1A HK1183058A1 (zh) 2010-07-05 2013-09-03 具有腸內腐敗物質的減少作用的雙歧桿菌

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JP2010152962 2010-07-05

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JP2018177752A (ja) * 2017-04-18 2018-11-15 国立大学法人東北大学 アルカリ性化剤による血液浄化
JPWO2018193648A1 (ja) * 2017-04-18 2020-02-27 国立大学法人東北大学 アルカリ性化剤による血液浄化
JP2020180094A (ja) * 2019-04-26 2020-11-05 森永乳業株式会社 腎機能障害予防又は改善用組成物、並びに、該腎機能障害予防又は改善用組成物を用いた医薬品組成物及び飲食品組成物
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JP2022072243A (ja) 2020-10-29 2022-05-17 帝人株式会社 腸内細菌叢改善用組成物及び腸内腐敗物質産生抑制用組成物
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WO2018193648A1 (ja) * 2017-04-18 2018-10-25 国立大学法人東北大学 アルカリ性化剤による血液浄化
JP2018177752A (ja) * 2017-04-18 2018-11-15 国立大学法人東北大学 アルカリ性化剤による血液浄化
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JP2020180094A (ja) * 2019-04-26 2020-11-05 森永乳業株式会社 腎機能障害予防又は改善用組成物、並びに、該腎機能障害予防又は改善用組成物を用いた医薬品組成物及び飲食品組成物
JP7309436B2 (ja) 2019-04-26 2023-07-18 森永乳業株式会社 腎機能障害予防又は改善用組成物、並びに、該腎機能障害予防又は改善用組成物を用いた医薬品組成物及び飲食品組成物
WO2021079869A1 (ja) * 2019-10-21 2021-04-29 ビオフェルミン製薬株式会社 尿毒素軽減剤

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