WO2022202904A1 - 腸管機能向上剤 - Google Patents
腸管機能向上剤 Download PDFInfo
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- WO2022202904A1 WO2022202904A1 PCT/JP2022/013542 JP2022013542W WO2022202904A1 WO 2022202904 A1 WO2022202904 A1 WO 2022202904A1 JP 2022013542 W JP2022013542 W JP 2022013542W WO 2022202904 A1 WO2022202904 A1 WO 2022202904A1
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- WIPO (PCT)
- Prior art keywords
- butyric acid
- agent
- acetic acid
- bacteria
- acid bacteria
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 162
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Images
Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT 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
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
-
- 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
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/724—Cyclodextrins
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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
- A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
Definitions
- the present invention relates to an intestinal function-improving agent containing cyclodextrin (hereinafter sometimes simply referred to as CD) and at least one of butyric acid bacteria, butyric acid, and acetic acid as active ingredients. Furthermore, the present invention provides a CD, an immunopotentiating agent, an agent for preventing infection with viruses or microorganisms, an antibacterial agent, a hydrogen generator and/or an antioxidant, which contains as active ingredients at least one of butyric acid bacteria, butyric acid, and acetic acid, and further CD It relates to a growth promoter for butyric acid bacteria containing as an active ingredient.
- CD intestinal function-improving agent containing cyclodextrin
- SCFAs short-chain fatty acids
- Butyric acid one of the SCFAs, is produced from Clostridium butyricum, which is used as a raw material for probiotics, etc., and is known to be an energy source and exhibit anti-inflammatory effects (for example, non-patented Reference 1).
- butyric acid bacteria and butyric acid have an infection-preventing effect against pathogenic E. coli, and that butyric acid may regulate gene expression related to viral infection and make it difficult to be infected with the virus. (For example, see Non-Patent Documents 2 and 3).
- Patent Document 3 in providing a function-enhancing composition that improves the bioavailability of active ingredients in general foods, foods with health claims, or health supplements, butyric acid bacteria and CD
- the effects of these per se and the specific effects of combining them on improving intestinal function were not examined, and were merely listed. Therefore, the present inventors investigated the effect of CD itself on butyric acid bacteria, and also studied the effect of combining CD with butyric acid bacteria and / or butyric acid, and attempted to provide a safe and useful new agent. rice field. Furthermore, the present inventors focused on hydrogen produced by butyric acid bacteria when assimilating carbon sources.
- Hydrogen produced in the gastrointestinal tract is known to have an antioxidant effect and scavenge highly reactive hydroxy radicals among reactive oxygen species (see, for example, Non-Patent Document 5). Therefore, we also investigated the effect of combining CD with butyric acid and/or butyric acid on hydrogen production, and tried to provide new agents.
- Hiroshi Oyaizu (2020) Professor of microbiology at the University of Tokyo teaches The only way not to be killed by Corona Jiyu Kokuminsha Co., Ltd. Motomichi Takahashi et. al., (2004). The effect of probiotic treatment with Clostridium butyricum on enterohemorrhagic Escherichia coli O157:H7 infection in mice FEMS Immunology and Medical Microbiology, 41, 219-226. Jing Li et. al., (2021). Butyrate Regulates COVID-19-Relevant Genes in Gut Epithelial Organoids From Normotensive Rats, 77, e13-e16. Taka-ichi Murayama et.
- An object of the present invention is to investigate the effect of CD itself on butyric acid bacteria, and to provide a safe and useful new agent etc. by combining CD with one or more of butyric acid bacteria, butyric acid, and acetic acid. .
- CD promotes the growth of butyric acid bacteria and the production of butyric acid and acetic acid.
- a combination of one or more of CD and butyric acid, butyric acid, or acetic acid improves intestinal function, enhances immune function, prevents infection with viruses or microorganisms, and is antibacterial against harmful microorganisms such as Staphylococcus aureus.
- the present inventors have completed the present invention based on the discovery that they have effects such as action, hydrogen generation action and/or antioxidant action.
- the present invention relates to an intestinal function-improving agent and the like shown in the following (1) to (15).
- An intestinal function-improving agent containing CD and at least one of butyric acid bacteria, butyric acid, and acetic acid as active ingredients.
- An immunopotentiating agent containing CD and at least one of butyric acid, butyric acid, and acetic acid as active ingredients.
- a virus or microorganism infection preventive agent containing CD and at least one of butyric acid, butyric acid, and acetic acid as active ingredients.
- An antibacterial agent containing CD and at least one of butyric acid bacteria, butyric acid, and acetic acid as active ingredients.
- a method for producing acetic acid comprising the step of imparting CD to butyric acid bacteria.
- a method for improving intestinal function comprising the step of administering CD and one or more of butyric acid bacteria, butyric acid, and acetic acid.
- a method for enhancing immunity comprising the step of administering CD and one or more of butyric acid bacteria, butyric acid, and acetic acid.
- a method for preventing viral or microbial infection comprising the step of administering CD and one or more of butyric acid, butyric acid, and acetic acid.
- a method of imparting an antibacterial effect which comprises administering CD and one or more of butyric acid bacteria, butyric acid, and acetic acid.
- a method for generating hydrogen and/or a method for imparting antioxidant action which comprises administering CD and at least one of butyric acid, butyric acid, and acetic acid.
- a butyric acid bacteria growth promoter a butyric acid production promoter, and an acetic acid production promoter, and a method for producing butyric acid or a method for producing acetic acid, using CD as an active ingredient.
- CD a butyric acid bacteria growth promoter
- a butyric acid production promoter a butyric acid production promoter
- an acetic acid production promoter a method for producing butyric acid or a method for producing acetic acid
- CD an active ingredient.
- Each agent obtained by the present invention can be used as it is as a food, health food, feed, quasi-drug, pharmaceutical, etc., or used as an active ingredient such as an anti-inflammatory agent or an immunostimulant. can. In addition, taking it as a supplement is expected to have beneficial effects on beauty and health.
- Example 6 It is a figure showing the growth promoting effect of butyric acid bacteria (Example 6). It is a figure showing the production promoting effect of butyric acid (Example 6). It is a figure showing the production promoting effect of acetic acid (Example 6). It is a figure showing the growth inhibitory effect of Staphylococcus aureus (Example 7). It is the figure which showed the increase amount of gas (Example 8). It is the figure which showed the hydrogen production amount (Example 8).
- intestinal function improving agent is all human, mouse, An agent that, when ingested by animals such as rats, rabbits, dogs, cats, horses, sheep, monkeys, cows, pigs and chickens, exhibits the following effects. That is, it has the effect of improving the intestinal function, the effect of enhancing the immune function, and preventing the infection of harmful viruses such as coronaviruses, influenza viruses, and viruses associated with upper respiratory tract infections, and harmful microorganisms such as Staphylococcus aureus and Escherichia coli. effects and the like.
- Such "intestinal function improving agent”, “immune enhancer”, “viral or microbial infection preventive agent”, “antibacterial agent” and “hydrogen generator and/or antioxidant” of the present invention are all CDs. Any agent containing at least one of butyric acid bacteria, butyric acid, and acetic acid as an active ingredient may be used. Moreover, in addition to these, the agent may contain other components such as more useful components and components necessary for maintaining the dosage form.
- the "proliferation promoter for butyric acid bacteria", “promoter for butyric acid production” and “promoter for acetic acid production” of the present invention all contribute to the growth of butyric acid bacteria, and the growth of butyric acid and acetic acid by imparting CD to butyric acid bacteria.
- Such a “proliferation promoter for butyric acid bacteria”, “promoter for butyric acid production” and “promoter for acetic acid production” of the present invention may be an agent containing CD as an active ingredient, and may further contain useful ingredients such as It may be an agent containing other ingredients such as ingredients necessary for maintaining the dosage form.
- the "method for producing butyric acid” or “method for producing acetic acid” of the present invention may be a method "including the step of imparting CD to butyric acid bacteria", and further includes other steps useful for producing butyric acid. It can be a method.
- CDs that can be used as active ingredients in “butyric acid production promoters” and “acetic acid production promoters”, and CDs that can be used in “methods for producing butyric acid” or “methods for producing acetic acid” are safe for animals. Any ingestible CD may be used, either commercially available or independently prepared.
- Such CDs include ⁇ -CD, ⁇ -CD, ⁇ -CD, maltosyl- ⁇ -CD, maltosyl- ⁇ -CD, maltosyl- ⁇ -CD, and the like.
- One type of these CDs may be used as an active ingredient, or two or more types may be used in combination.
- Examples of commercially available ⁇ -CD include Pure Fiber (Cosana Co., Ltd.) and indigestible ⁇ -oligosaccharide (Cosana Co., Ltd.).
- butyric acid that can be used as an active ingredient of "intestinal function improving agent", “immune enhancer”, “viral or microbial infection preventive agent”, “antibacterial agent” and “hydrogen generator and / or antioxidant” Any bacteria can be used as long as they can be safely ingested by animals.
- butyricum TO-A strain Toa Shinyaku Co., Ltd.
- examples of butyric acid and acetic acid include butyric acid and acetic acid produced by these butyric bacteria and commercially available butyric acid and acetic acid.
- the “agent” may be administered in an amount that exhibits an effect in the ingested animal.
- the amount of CD contained in each agent and ingested is preferably about 0.001 to 10 g/day, particularly preferably about 2 to 10 g/day.
- the amount of butyric acid bacteria is preferably about 1 to 10 10 CFU/day, more preferably about 10 6 to 10 8 CFU/day.
- the amount of butyric acid is preferably about 0.00001 to 5 g/day, more preferably about 0.1 to 2 g/day. Furthermore, the amount of acetic acid is preferably about 0.00001 to 5 g/day, more preferably about 0.1 to 3 g/day.
- Example> 1 Carbohydrate 1) ⁇ -CD (CAVAMAXW6 (registered trademark) Food, CycloChem Bio Co., Ltd.) 2) Galacto-oligosaccharide (GOS) (galacto-oligosaccharide, FUJIFILM Wako Pure Chemical Industries, Ltd.) 3) Fructo-oligosaccharide (FOS) (fructo-oligosaccharide, FUJIFILM Wako Pure Chemical Industries, Ltd.) 4) Indigestible dextrin (ID) (Fibersol (registered trademark) 2, Matsutani Chemical Industry Co., Ltd.) 5) Isomaltodextrin (IMD) (Fiberixa (registered trademark), Hayashibara Co., Ltd.) 6) Inulin (INL) (Inulin, FUJIFILM Wako Pure Chemical Industries, Ltd.) 7) Polydextrose (PDX) (
- Basic medium GAM bouillon “Nissui” (Nissui Pharmaceutical Co., Ltd.)
- Sugar-free medium for assimilation test Semi-fluid medium for GAM glycolysis "Nissui” (Nissui Pharmaceutical Co., Ltd.) After adding this medium to cold water and stirring well, the agar was removed by filtration and then sterilized in an autoclave for use.
- Staphylococcus aureus Staphylococcus aureus IFO 12732 Medium: GAM bouillon “Nissui” (Nissui Pharmaceutical Co., Ltd.)
- Example 1 Method for Producing Intestinal Function-Improving Agent ⁇ -CD was used as an intestinal function-improving agent in combination with at least one of butyric acid bacteria, butyric acid, and acetic acid.
- Example 2 Method for producing immunopotentiator ⁇ -CD was used as an immunopotentiator in combination with one or more of butyric acid bacteria, butyric acid and acetic acid.
- Example 3 Method for Producing Agent for Preventing Virus or Microorganism Infection ⁇ -CD and one or more of butyric acid bacteria, butyric acid, and acetic acid were combined and used as an agent for preventing virus or microorganism infection.
- Example 4 Method for producing antibacterial agent ⁇ -CD was used as an antibacterial agent in combination with one or more of butyric acid bacteria, butyric acid, and acetic acid.
- Example 5 Method for Producing Hydrogen Generating Agent and/or Antioxidant A combination of ⁇ -CD and at least one of butyric acid bacteria, butyric acid and acetic acid was used as a hydrogen generating agent and/or antioxidant.
- Example 7 Examination of antibacterial action Staphylococcus aureus alone, coexistence of Staphylococcus aureus and 0.5w/v% ⁇ -CD, coexistence of Staphylococcus aureus and butyric acid bacteria, or coexistence of Staphylococcus aureus and butyric acid bacteria with 0.5w/v % ⁇ -CD was added and cultured at 37°C under anaerobic conditions, and the number of Staphylococcus aureus was counted 20 hours after the start of culture. The final concentration of Staphylococcus aureus was 7.5 ⁇ 10 2 CFU/mL, and the final concentration of Butyric acid bacteria was 9.4 ⁇ 10 6 CFU/mL.
- the number of Staphylococcus aureus bacteria was determined by the dilution plate method, that is, by spreading a moderately diluted culture solution on an agar medium, incubating it at 37°C under aerobic conditions, and counting the number of formed colonies.
- the test results were expressed as the mean ⁇ standard error of three samples.
- ⁇ -CD alone showed almost no growth inhibitory effect, but the addition of butyric acid bacteria remarkably inhibited the growth of Staphylococcus aureus. The addition was shown to completely suppress the growth of Staphylococcus aureus. Therefore, from this result, it was confirmed that the combination of ⁇ -CD and butyric acid bacteria exhibits strong antibacterial properties against harmful bacteria such as Staphylococcus aureus.
- Example 8 Investigation of hydrogen generating action and/or antioxidant action A basal medium was inoculated with butyric acid bacteria colonies and cultured at 37°C for 20 hours under anaerobic conditions (preculture). Each saccharide was dissolved at 1 w/v% in 100 mL of the sugar-free medium for assimilation test, and the pre-culture solution was added at 5 v/v% and cultured at 37°C for 24 hours under anaerobic conditions in a sealed container. (main culture). The change in the volume at the end of the culture from the volume at the start of the main culture was examined to calculate the amount of gas increase.
- the hydrogen concentration in the gas after culture was measured using a hydrogen detector tube ( Komyo Rikagaku Kogyo Co., Ltd.). From the measured hydrogen concentration and gas increase, the amount of hydrogen produced by the culture (mL) was calculated by the following formula. The test results were expressed as the mean ⁇ standard error of 3 to 5 samples. For statistical processing, statistical analysis software Pharmaco Analyst I (Ver. 13.1.1; Three S Japan, Tokyo, Japan) was used, and Dunnett's test was performed.
- Hydrogen is known to have an antioxidant effect, oxidize biological components such as proteins, lipids, and nucleic acids, and act to eliminate hydroxyl radicals that induce diseases such as arteriosclerosis, myocardial infarction, and cancer. . Therefore, it was suggested that the ingestion of ⁇ -CD produces hydrogen and exerts a high antioxidant effect.
- a butyric acid bacteria growth promoter a butyric acid production promoter, and an acetic acid production promoter, and a method for producing butyric acid or a method for producing acetic acid, using CD as an active ingredient.
- CD a butyric acid bacteria growth promoter
- a butyric acid production promoter a butyric acid production promoter
- an acetic acid production promoter a method for producing butyric acid or a method for producing acetic acid
- CD an active ingredient.
- an agent that can exert Each agent obtained by the present invention can be used as it is as a food, health food, feed, quasi-drug, pharmaceutical, etc., or used as an active ingredient such as an anti-inflammatory agent or an immunostimulant. can.
- taking it as a supplement is expected to have beneficial effects on beauty and health.
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Abstract
Description
また、酪酸菌を腸内細菌フリーマウスに投与すると腸内IgAが増加する作用があることが知られており(例えば、非特許文献4参照)、酪酸菌自体を整腸剤や栄養剤として用いるにあたり、環状デキストリンであるCDと混合して乾燥させることで無臭菌体とする技術も開示されている(例えば、特許文献2参照)。しかし、この技術は酪酸を胃腸に送達することや無臭化することを目的とするものであり、いずれもCD自体の胃腸に与える効果については示唆も検討もされていなかった。
そこで、本発明者らは、CDそのものが酪酸菌に与える効果を調べるとともに、CDを酪酸菌及び/又は酪酸と組み合わせることによる効果の検討も行い、安全で有用な新たな剤等の提供を試みた。
さらに、本発明者らは、酪酸菌が炭素源を資化する際に産生する水素にも着目した。消化管内で産生された水素は抗酸化作用を有し、活性酸素種の中でも高い反応性を有するヒドロキシラジカルを消去すること等が知られている(例えば、非特許文献5参照)。そこで、CDを酪酸菌及び/又は酪酸と組み合わせることによる、水素の産生への効果についての検討も行い、新たな剤等の提供を試みた。
(1)CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を有効成分として含む腸管機能向上剤。
(2)CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を有効成分として含む免疫増強剤。
(3)CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を有効成分として含むウイルス又は微生物の感染予防剤。
(4)CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を有効成分として含む抗菌剤。
(5)CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を有効成分として含む水素発生剤及び/又は抗酸化剤。
(6)CDを有効成分として含む酪酸菌の増殖促進剤。
(7)CDを有効成分とする酪酸の産生促進剤。
(8)CDを有効成分とする酢酸の産生促進剤。
(9)CDを酪酸菌に付与する工程を含む酪酸の製造方法。
(10)CDを酪酸菌に付与する工程を含む酢酸の製造方法。
(11)CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を投与する工程を含む、腸管機能向上方法。
(12)CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を投与する工程を含む、免疫増強方法。
(13)CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を投与する工程を含む、ウイルス又は微生物の感染予防方法。
(14)CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を投与する工程を含む、抗菌作用の付与方法。
(15)CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を投与する工程を含む、水素発生方法及び/又は抗酸化作用の付与方法。
本発明によって得られる各剤はそのまま食品、健康食品、飼料、医薬部外品や医薬品等として利用したり、抗炎症剤や免疫賦活剤等の有効成分として利用したりするなど様々な用途に使用できる。また、サプリメントとして摂取することで美容・健康面への有益な効果が期待される。
即ち、腸管機能を向上する効果、免疫機能を増強する効果、コロナウイルス、インフルエンザウイルス又は上気道感染症関連ウイルス等の有害なウイルスや、黄色ブドウ球菌、大腸菌等の有害な微生物の感染を予防する効果等が挙げられる。また、これらの微生物の増殖を抑制する効果、これらの微生物によって産生される毒素等の作用を阻害する効果、消化管内において水素を発生する効果や水素の産生を促進する効果、この発生または産生した水素によって抗酸化作用を発揮する効果等が挙げられる。
このような本発明の「腸管機能向上剤」、「免疫増強剤」、「ウイルス又は微生物の感染予防剤」、「抗菌剤」及び「水素発生剤及び/又は抗酸化剤」はいずれもCDと酪酸菌、酪酸又は酢酸をいずれか一種以上を有効成分として含む剤であればよい。また、これらに加えて、さらに有用な成分や剤形を保つのに必要な成分等、その他の成分を含む剤であってもよい。
このような本発明の「酪酸菌の増殖促進剤」、「酪酸の産生促進剤」や「酢酸の産生促進剤」はいずれもCDを有効成分として含む剤であればよく、さらに有用な成分や剤形を保つのに必要な成分等、その他の成分を含む剤であってもよい。
このようなCDとしてα-CD、β-CD、γ-CD、マルトシル-α-CD、マルトシル-β-CD又はマルトシル-γ-CD等が挙げられる。これらのCDは有効成分として1種類用いてもよく、2種類以上を組み合わせて用いても良い。
市販のα-CDとして例えばピュアファイバー(株式会社コサナ)、難消化性αオリゴ糖(株式会社コサナ)等が挙げられる。
また酪酸及び酢酸としては、これらの酪酸菌が産生した酪酸及び酢酸や市販の酪酸及び酢酸等が挙げられる。
例えば、摂取する動物がヒトである場合、各剤に含まれ、摂取されるCDの量は0.001~10g/日程度であることが好ましく、特に2~10g/日程度であることが好ましい。同様に酪酸菌の量は1~1010 CFU/日程度であることが好ましく、特に106~108 CFU/日程度であることが好ましい。酪酸の量は0.00001~5g/日程度であることが好ましく、特に0.1~2g/日程度であることが好ましい。さらに酢酸の量は0.00001~5g/日程度であることが好ましく、特に0.1~3g/日程度であることが好ましい。
<試料>
1.糖質
1)α-CD(CAVAMAXW6(登録商標)Food、株式会社シクロケムバイオ)
2)ガラクトオリゴ糖(GOS)(ガラクトオリゴ糖、富士フイルム和光純薬株式会社)
3)フラクトオリゴ糖(FOS)(フルクトオリゴ糖、富士フイルム和光純薬株式会社)
4)難消化性デキストリン(ID)(ファイバーソル(登録商標)2、松谷化学工業株式会社)
5)イソマルトデキストリン(IMD)(ファイバリクサ(登録商標)、株式会社林原)
6)イヌリン(INL)(イヌリン、富士フイルム和光純薬株式会社)
7)ポリデキストロース(PDX)(スターライト(登録商標)III、株式会社光洋商会)
8)グァーガム分解物(PHGG)(サンファイバー(登録商標)、株式会社タイヨーラボTL1)
9)ラクトスクロース(LS)(オリゴのおかげ(登録商標) LS-90P、塩水港精糖株式会社)
Clostridium butyricum M-II588(エースバイオプロダクト株式会社)
基本培地:GAMブイヨン「ニッスイ」(日水製薬株式会社)
資化性試験用無糖培地:GAM糖分解用半流動培地「ニッスイ」(日水製薬株式会社)
冷水にこの培地を加えてよく撹拌した後、ろ過により寒天を除去してからオートクレーブ滅菌して用いた。
Staphylococcus aureus IFO 12732
培地:GAMブイヨン「ニッスイ」(日水製薬株式会社)
腸管機能向上剤の製造方法
α-CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を組み合わせて腸管機能向上剤として用いた。
免疫増強剤の製造方法
α-CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を組み合わせて免疫増強剤として用いた。
ウイルス又は微生物の感染予防剤の製造方法
α-CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を組み合わせてウイルス又は微生物の感染予防剤として用いた。
抗菌剤の製造方法
α-CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を組み合わせて抗菌剤として用いた。
水素発生剤及び/又は抗酸化剤の製造方法
α-CDと、酪酸菌、酪酸又は酢酸のいずれか一種以上を組み合わせて水素発生剤及び/又は抗酸化剤として用いた。
酪酸菌の増殖促進効果、酪酸及び/又は酢酸の産生促進効果の検討
基本培地に酪酸菌コロニーを接種して、嫌気条件下、37℃で20時間培養した(前培養)。前培養液を遠心分離(3,700rpm、8min)し、酪酸菌が含まれるペレットを資化性試験用無糖培地で再懸濁させた(660nmにおける濁度が約1.2)。新たな資化性試験用無糖培地に各種糖質をそれぞれ1w/v%を溶解させて、酪酸菌が含まれる再懸濁液を1v/v%で加えて密閉容器内で嫌気条件下、37℃で培養した(本培養)。培養開始から20時間後の660nmにおける濁度変化(ΔOD)を調べ、添加した各種糖質が資化されて酪酸菌が増殖しているか否かを評価した。
また、培養後の培養液を採取し、ツーバンドpH試験紙(DUOTEST)を用いて pHを測定するとともに、培養液中に含まれる酪酸及び酢酸の量をParkerらの方法(S. G. Parker, et al., Jounal of Functional Foods, 31, 266-273 (2017))に従ってN-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide(MTBSTFA)で誘導化した後にGC-FIDを用いて測定し、酪酸及び酢酸の産生が促進されているか否かを評価した。
試験結果はサンプル数3つの平均値±標準誤差として表した。統計処理は統計解析ソフトPharmaco Analyst I (Ver. 13.1.1; Three S Japan, Tokyo, Japan) を使用し、Dunnett検定を行った。
従って、この結果よりα-CDを摂取することによって、腸内細菌叢における酪酸菌の数が顕著に増加するとともに、酪酸及び酢酸の量も増加でき、腸管機能の向上に働くことが示唆された。
抗菌作用の検討
黄色ブドウ球菌単独、黄色ブドウ球菌と0.5w/v% α-CDを共存、黄色ブドウ球菌と酪酸菌を共存、又は黄色ブドウ球菌と酪酸菌を共存させたものに0.5w/v% α-CDを加えて嫌気条件下、37℃で培養を行い、培養開始から20時間後に黄色ブドウ球菌数を数えた。黄色ブドウ球菌の添加量は終濃度として7.5×102 CFU/mL、酪酸菌の添加量は終濃度として9.4×106 CFU/mLとした。黄色ブドウ球菌数については希釈平板法、すなわち適度に希釈した培養液を寒天培地に広げて好気条件下、37℃で培養を行い、形成されたコロニー数を計測することによって測定した。試験結果はサンプル数3つの平均値±標準誤差として表した。
従って、この結果より、α-CDと酪酸菌の組み合わせが、黄色ブドウ球菌等の有害細菌に対して強い抗菌性を発揮することが確認できた。
水素発生作用及び/又は抗酸化作用の検討
基本培地に酪酸菌コロニーを接種して、嫌気条件下、37℃で20時間培養した(前培養)。資化性試験用無糖培地100mLに各種糖質をそれぞれ1w/v%で溶解させて、前培養液を5v/v%で加えて密閉容器内で嫌気条件下、37℃で24時間培養した(本培養)。
本培養開始時の体積から培養終了時の体積の変化を調べ、気体増加量を算出した。また、水素検知管(光明理化学工業株式会社)を用いて培養後の気体中の水素濃度を測定した。測定された水素濃度と気体増加量から、培養による水素産生量(mL)を次の計算式により算出した。
なお、試験結果はサンプル数3~5の平均値±標準誤差として表した。統計処理は統計解析ソフトPharmaco Analyst I(Ver. 13.1.1; Three S Japan, Tokyo, Japan)を使用し、Dunnett検定を行った。
水素は抗酸化作用を有し、タンパク質や脂質、核酸などの生体成分を酸化し、動脈硬化、心筋梗塞、がんなどの疾病を誘引するヒドロキシラジカルの消去等に作用することが知られている。従って、α-CDの摂取によって水素の発生が起こることにより、高い抗酸化作用が発揮されることが示唆された。
本発明によって得られる各剤はそのまま食品、健康食品、飼料、医薬部外品や医薬品等として利用したり、抗炎症剤や免疫賦活剤等の有効成分として利用したりするなど様々な用途に使用できる。また、サプリメントとして摂取することで美容・健康面への有益な効果が期待される。
Claims (6)
- シクロデキストリンと、酪酸菌、酪酸又は酢酸のいずれか一種以上を有効成分として含む腸管機能向上剤。
- シクロデキストリンと、酪酸菌、酪酸又は酢酸のいずれか一種以上を有効成分として含む免疫増強剤。
- シクロデキストリンと、酪酸菌、酪酸又は酢酸のいずれか一種以上を有効成分として含むウイルス又は微生物の感染予防剤。
- シクロデキストリンと、酪酸菌、酪酸又は酢酸のいずれか一種以上を有効成分として含む抗菌剤。
- シクロデキストリンと、酪酸菌、酪酸又は酢酸のいずれか一種以上を有効成分として含む水素発生剤及び/又は抗酸化剤。
- シクロデキストリンを有効成分として含む酪酸菌の増殖促進剤。
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JP2005034135A (ja) | 2003-06-30 | 2005-02-10 | Meiji Seika Kaisha Ltd | 一般食品、保健機能食品または健康補助食品の機能増強組成物及びその方法 |
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