WO2023190710A1 - Composition, food and beverage, pharmaceutical agent, and use of inulin - Google Patents

Composition, food and beverage, pharmaceutical agent, and use of inulin Download PDF

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Publication number
WO2023190710A1
WO2023190710A1 PCT/JP2023/012863 JP2023012863W WO2023190710A1 WO 2023190710 A1 WO2023190710 A1 WO 2023190710A1 JP 2023012863 W JP2023012863 W JP 2023012863W WO 2023190710 A1 WO2023190710 A1 WO 2023190710A1
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Prior art keywords
acid
inulin
composition according
infection
cov
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PCT/JP2023/012863
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French (fr)
Japanese (ja)
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保典 中山
真嗣 福田
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帝人株式会社
株式会社メタジェン
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Publication of WO2023190710A1 publication Critical patent/WO2023190710A1/en

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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
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/206—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin
    • A23L29/244—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin from corms, tubers or roots, e.g. glucomannan
    • 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
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • 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
    • A61K31/733—Fructosans, e.g. inulin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • 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
    • 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

Definitions

  • the present invention relates to compositions, food and drink products, pharmaceuticals, and uses of inulin.
  • the new coronavirus (SARS-CoV-2), which was first reported in China at the end of 2019, is an RNA virus that belongs to the order Nidovirales and the family Coronaviridae, and has caused a global pandemic. It has been reported that those infected with coronavirus infection (COVID-19) caused by the new coronavirus are accompanied by acute respiratory symptoms such as fever and difficulty breathing, and if the symptoms worsen, pneumonia can develop.
  • compositions that can suppress coronavirus infections caused by the new coronavirus have not been sufficiently developed, and the development of effective compositions is desired. Further, it is desirable that the composition etc. be in a form that can be easily taken in on a daily basis.
  • the present invention aims to provide a composition that can be easily taken on a daily basis and suppresses infection with the new coronavirus.
  • the main invention of the present invention for solving the above problems is as follows: A composition containing inulin and inhibiting SARS-CoV-2 infection.
  • the present invention it is possible to provide a composition that can be easily taken on a daily basis and suppresses infection with the new coronavirus.
  • FIG. 2 is a diagram showing bacterial groups that were significantly different between a control group and a test group in an example of the present invention.
  • FIG. 2 is a diagram showing bacterial groups that were significantly different between a control group and a test group in an example of the present invention.
  • FIG. 2 is a diagram showing bacterial groups that were significantly different between a control group and a test group in an example of the present invention.
  • FIG. 2 is a diagram showing bacterial groups that were significantly different between a control group and a test group in an example of the present invention.
  • FIG. 2 is a diagram showing bacterial groups that were significantly different between a control group and a test group in an example of the present invention.
  • FIG. 2 is a diagram showing bacterial groups that were significantly different between a control group and a test group in an example of the present invention.
  • FIG. 2 is a diagram showing bacterial groups that have a high occupancy rate but are not significantly different between a control group and a test group in an example of the present invention.
  • FIG. 2 is a diagram showing bacterial groups that have a high occupancy rate but are not significantly different between a control group and a test group in an example of the present invention.
  • FIG. 2 is a diagram showing bacterial groups that have a high occupancy rate but are not significantly different between a control group and a test group in an example of the present invention.
  • FIG. 2 is a diagram showing short chain fatty acids as metabolites in Examples of the present invention.
  • FIG. 2 is a diagram showing short chain fatty acids as metabolites in Examples of the present invention.
  • FIG. 2 is a diagram showing short chain fatty acids as metabolites in Examples of the present invention.
  • FIG. 2 is a diagram showing primary and secondary bile acids as metabolites in an example of the present invention.
  • FIG. 2 is a diagram showing conjugated bile acids as metabolites in Examples of the present invention.
  • FIG. 2 is a diagram showing conjugated bile acids as metabolites in Examples of the present invention.
  • FIG. 2 is a diagram showing conjugated bile acids as metabolites in Examples of the present invention.
  • FIG. 2 is a diagram showing conjugated bile acids as metabolites in Examples of the present invention.
  • compositions, food and drink products, pharmaceuticals, and uses of inulin will be described based on the drawings. Note that the present invention is not limited to this embodiment.
  • the present invention includes, for example, the following configuration.
  • [Item 1] A composition containing inulin and inhibiting SARS-CoV-2 infection.
  • [Item 2] The composition according to item 1, wherein the inulin has a number average molecular weight (Mn) of 500 or more and 4000 or less.
  • [Item 3] The composition according to item 1 or 2, wherein the inulin has an average degree of polymerization (DP) of 3 or more and 30 or less.
  • DP average degree of polymerization
  • [Item 5] 5.
  • [Item 7] 7 The composition according to any one of items 1 to 6, which increases the secretion of bile acids.
  • item 8 The composition according to any one of items 1 to 6, which inhibits SARS-CoV-2 infection by increasing and/or decreasing bile acid secretion.
  • the bile acids in the increase in bile acid secretion include lithocholic acid (LCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), cholic acid (CA), glycodeoxycholic acid (GDCA), taurolithochol at least one selected from the group consisting of acid (TLCA), tauroursodeoxycholic acid (TUDCA), taurodeoxycholic acid (TDCA), and taurocholic acid (TCA), Item 8, wherein the bile acid in the reduction of bile acid secretion is at least one selected from the group consisting of glycoursodeoxycholic acid (GUDCA), glycocholic acid (GCA), and taurochenodeoxycholic acid (TCDCA).
  • LCA lithocholic acid
  • UDCA ursodeoxycholic acid
  • DCA deoxycholic acid
  • CA glycodeoxycholic acid
  • GDCA glycodeoxycholic acid
  • TCA taurolithochol at least one selected from the group consisting
  • [Item 10] The composition according to item 9, wherein the bile acid in increasing secretion of bile acids is at least one selected from the group consisting of cholic acid (CA), deoxycholic acid (DCA), and lithocholic acid (LCA). thing.
  • [Item 11] Increase in at least one bacterium selected from the group consisting of Treponema 2, Parabacteroides, Bifidobacterium and A2 and/or Eisenbergiella, Ruminiclostridium 5, Coprostanoligenes group, R uminiclostridium 1, Lactococcus, Anaeroplasma, Butyricimonas, Tyzzerella and Pygmaiobacter. 11.
  • composition according to any one of items 1 to 10 which suppresses SARS-CoV-2 infection by reducing at least one bacterium.
  • item 12 A food or drink containing the composition according to any one of items 1 to 11, which suppresses SARS-CoV-2 infection.
  • item 13 A pharmaceutical product containing the composition according to any one of items 1 to 11, which suppresses SARS-CoV-2 infection.
  • item 14 Use of inulin to increase bile acid secretion.
  • the infectious disease caused by the new coronavirus is the new coronavirus infection (COVID-19).
  • the new coronavirus includes not only conventional strains but also mutant strains.
  • Such mutant strains include, for example, mutant strains with the N501Y mutation, such as the mutant strain confirmed in the UK (VOC-202012/01), the mutant strain confirmed in South Africa (501Y.V2), and the variant strain confirmed in Brazil.
  • mutant strains with the N501Y mutation such as the mutant strain confirmed in the UK (VOC-202012/01
  • the mutant strain confirmed in South Africa (501Y.V2) the mutant strain confirmed in Brazil
  • the variant strain confirmed in Brazil examples of the "mutant strain with the E484K mutation” include the mutant strain confirmed in South Africa (501Y.V2) and the mutant strain confirmed in Brazil (501Y.V3). etc., but are not limited to these.
  • “Infection control” includes the concept of treatment or prevention of the new coronavirus infection (COVID-19), including the concept of inhibiting or delaying the entry of the new coronavirus (SARS-CoV-2) into the body, This includes promoting the elimination of coronavirus (SARS-CoV-2) from the body.
  • treatment refers to reducing or improving one or more symptoms caused by infection with the new coronavirus, suppressing the severity of the disease, and delaying the progression of the disease. means. "Prevention” means inhibiting the onset of the new coronavirus infection, reducing the risk of onset, or delaying the onset of the disease.
  • inulin to asymptomatic coronavirus carriers (those who have no symptoms but have been confirmed positive for coronavirus through PCR (polymerase chain reaction) tests, etc.) to prevent the onset of symptoms and reduce the risk of infection to others. Treatment or prevention also includes administering.
  • inulin is a polysaccharide classified as a water-soluble dietary fiber contained in various plants such as Asteraceae and Iridaceae, and is a polysaccharide in which multiple fructose molecules are bonded to glucose. It is a combination. Specifically, inulin is a linear fructan in which D-fructofuranose is polymerized with ⁇ 2 ⁇ 1 glycosidic bonds among fructans known as water-soluble dietary fibers, which are polysaccharide polymers of fructose with glucose at the end.
  • inulin can also include “branched inulin”, which is a branched fructan having a ⁇ 2 ⁇ 1 glycosidic bond and at least one ⁇ 2 ⁇ 6 glycosidic bond.
  • average degree of polymerization refers to the average number of saccharide units (fructose and glucose units) in inulin.
  • composition contains inulin and suppresses SARS-CoV-2 infection.
  • Inulin increases and/or decreases the number of specific bacteria in the intestines, increases and/or decreases metabolites produced by the bacteria (e.g. short chain fatty acids and secondary bile acids), and changes in these. It is thought that infection with SARS-CoV-2 is suppressed by increasing and/or decreasing metabolites (eg, bile acids) secreted from the host via .
  • metabolites eg, bile acids
  • short chain fatty acids produced by intestinal bacteria act on immune cells in the lymphoid follicles of the large intestine and enhance immunoglobulin A (IgA) production in the large intestine.
  • IgA immunoglobulin A
  • ursodeoxycholic acid a type of secondary bile acid, binds to angiotensin-converting enzyme 2 (ACE2), which is the first receptor that SARS-CoV-2 binds to during infection, and SARS-CoV-2.
  • ACE2 angiotensin-converting enzyme 2
  • composition containing inulin according to the present embodiment can be easily taken on a daily basis and can provide a method for suppressing infection with the new coronavirus.
  • the inulin contained in the composition according to the present embodiment may have a number average molecular weight (Mn) of 500 or more and 7,000 or less, and may have a number average molecular weight of 500 or more and 4,000 or less, and contains only an arbitrary number average molecular weight. It can be done.
  • the average molecular weight of inulin can be determined by comparing it with a known standard pullulan using GPC chromatography.
  • any method that is normally used in this field may be used as a method for adjusting the number average molecular weight of inulin to a desired value. For example, a method of separating extracted inulin itself, a method of separating extracted inulin, Examples include a method of decomposing inulin itself.
  • inulin can have an average degree of polymerization (DP) in a range of 2 or more and 100 or less, 2 or more and 60 or less, and 3 or more and 30 or less.
  • the average degree of polymerization of inulin can be determined by, for example, the top of the peak in the analysis result obtained by a conventional analysis method such as liquid chromatography, gas chromatography, anion chromatography, or the like.
  • a method for adjusting the average degree of polymerization of inulin to a desired value any method that is normally used in this field may be used. The same method as the adjustment method can be mentioned.
  • inulin may be linear, branched, or modified.
  • the average chain length of linear inulin can be in the range of 2 or more and 100 or less, it can be in the range of 2 or more and 60 or less, it can be 5 or more and 30 or less, and it can be 8 or more and 13 or less. Something can happen.
  • Such linear inulin can be, for example, Inulia (registered trademark), Frutafit (registered trademark), or Raftiline (registered trademark) in the case of inulin derived from chicory root, and in the case of using inulin produced by enzymatic synthesis.
  • Fuji FF registered trademark
  • Branched-chain inulin is known to be abundant in agave, a succulent plant that is the raw material for tequila (J. Agric. Food Chem., (2003) 51 (27), pp 7835 -7840, J. Agric. Food Chem., (2006) 54 (20), pp 7832-7839, etc.).
  • the branched chain inulin in the present invention is not particularly limited, but can be obtained, for example, from the agave by the conventional method described in WO 07/142306 pamphlet, etc., and is typically shredded from pi ⁇ a, which is the stem part of the agave. , included in processed products that have undergone juice extraction, filtration, purification, concentration, powder drying, etc. Such a processed product is also called agaba inulin.
  • inulin may be collected from a plant rich in inulin by a method well known to those skilled in the art.
  • plants include chicory, Jerusalem artichoke, dahlia, garlic, chive, onion, dandelion, and burdock.
  • inulin can be produced by decomposing chicory root using an enzymatic method, synthesizing it from sugarcane using an enzymatic method, or producing chicory root without using an enzymatic method, which has been processed to the extent that it can be used as a food. You can use the
  • Examples of the form of the composition according to this embodiment include those consisting only of inulin, as well as forms such as pharmaceuticals, food additives, and supplements.
  • the dosage forms include solid forms such as powders, tablets, sugar-coated agents, capsules, granules, dry syrups, liquids, syrups, drops, and drinks.
  • a liquid dosage form can be mentioned.
  • the composition according to the present embodiment can be in the form of ordinary food and drink such as confectionery, beverages, processed foods, health foods, and infant foods, in addition to those consisting only of inulin.
  • inulin When it is in the form of a food or drink, it can be manufactured by adding active ingredients in a normal manufacturing process.
  • Inulin has a sweetness level of about 20, and its taste, physical properties, and processability are similar to sucrose, so inulin is used to replace part or all of sugar in the manufacturing process of various foods and drinks.
  • the amount of intake that can be handled in the same manner to produce various foods and drinks can be any amount and any period of intake.
  • inulin added to the food composition or beverage composition there is no particular restriction on the amount of inulin added to the food composition or beverage composition, and it can be 0.1% by weight or more and 10% by weight or less, and 1% by weight or more, based on the food composition or beverage composition. It can be up to 5% by weight.
  • the intake or administration amount can be, for example, 0.015 g/kg or more per day.
  • the intake amount is not limited to once a day, but may be divided into multiple doses.
  • the amount of intake can be any amount and any period of intake.
  • the composition according to this embodiment can be used to suppress SARS-CoV-2 infection.
  • the bile acids whose secretion is increased by ingesting a composition containing inulin are lithocholic acid (LCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), and cholic acid (CA). , glycodeoxycholic acid (GDCA), taurolithocholic acid (TLCA), tauroursodeoxycholic acid (TUDCA), taurodeoxycholic acid (TDCA), and taurocholic acid (TCA).
  • the bile acid whose secretion is decreased may be at least one selected from the group consisting of glycoursodeoxycholic acid (GUDCA), glycocholic acid (GCA), and taurochenodeoxycholic acid (TCDCA).
  • the bacteria that increase by ingesting the composition containing inulin are at least one bacteria selected from the group consisting of Treponema 2, Parabacteroides, Bifidobacterium, and A2, and the bacteria that decrease are Eisenbergiella, Ruminiclostridium 5, Coprostanoligenes group, Ruminiclostridium 1, Lactococcus, Anaeroplasma, Butyricimonas, Tyzzerel
  • the microorganism may be at least one bacterium selected from the group consisting of P. la and Pygmaiobacter.
  • mice 4-week-old female Syrian hamsters purchased from Japan SLC Co., Ltd. were divided into a control group (AIN-93G feed) and a test group (AIN-93G feed + 5% inulin diet). The mice were reared for 2 weeks under 12-hour light/dark cycle with free access to food and water under (pathogen-free) conditions. Inulin extracted and purified from chicory root (Inulia (registered trademark) IQ (Teijin Ltd.)) was used as inulin.
  • Inulia registered trademark
  • IQ Teijin Ltd.
  • SARS-CoV-2/UT-NCGM02/Human/2020/Tokyo was infected via the intranasal route.
  • Viral infection was performed by intranasally applying 2 ⁇ 10 6 pfu of SARS-CoV-2 to Syrian hamsters under complete anesthesia with intraperitoneal injection of pentobarbital sodium (day of infection was determined). 0). These Syrian hamsters were raised for 14 days under the same conditions as before virus infection, and survival and death were confirmed.
  • SILVA database OTUs obtained by clustering SILVA SSU Ref provided by silva using a 99% threshold were used (hereinafter referred to as the SILVA database).
  • each base sequence is assigned to the most similar OTU in the SILVA database, and by counting the number of base sequences assigned (mapped) to each OTU, the bacterial phylogenetic composition of the intestinal flora can be quantified. It became.
  • metabolites were extracted from stool by liquid-liquid extraction using an organic solvent and divided into a sample for short-chain fatty acid measurement and a sample for bile acid measurement. After derivatizing the short-chain fatty acid measurement sample, an internal standard substance for elution time correction was directly added to the bile acid measurement sample. Short chain fatty acids were measured using GC-MS, and bile acids were measured using LC-TOF/MS. Metabolites were measured using LC-TOF/MS, and the column retention time, mass-to-charge ratio (m/z), and peak area of the detected peaks were obtained.
  • Figures 3 to 7 show bacterial groups with significant differences between the control group and inulin intake group
  • Figures 8 to 10 show bacterial groups with high occupancy rates but no significant differences between the control group and inulin intake group. show. From these results, compared to the control group, Treponema 2, Parabacteroides, Bifidobacterium, and A2 significantly increased in the test group, and Eisenbergiella, Ruminiclostridium 5, and Coprostanoligene.
  • s group Ruminiclostridium 1, Lactococcus, Anaeroplasma, Butyricimonas, Tyzzerella, Pygmaiobacter decreased significantly.
  • a P value of less than 0.05 was determined to be significant using Mann-Whitney U test, which is commonly performed in this field.
  • FIG 11 shows the average value of short chain fatty acids among metabolites
  • Figure 12 shows the average value of bile acids among metabolites.
  • FIGS. 13 to 15 show short chain fatty acids as metabolites
  • FIG. 16 shows primary and secondary bile acids as metabolites
  • FIGS. 17 to 19 show conjugated bile acids as metabolites. From these results, compared to the control group, the test group had lower levels of lithocholic acid (LCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), cholic acid (CA), and glycodeoxycholic acid (GDCA).
  • LCA lithocholic acid
  • UDCA ursodeoxycholic acid
  • DCA deoxycholic acid
  • CA cholic acid
  • GDCA glycodeoxycholic acid
  • taurolithocholic acid TLCA
  • tauroursodeoxycholic acid TUDCA
  • taurodeoxycholic acid TDCA
  • taurocholic acid TCA
  • GUA glycoursodeoxycholic acid
  • GCA glycocholic acid
  • TCDCA taurochenodeoxycholic acid

Abstract

[Problem] To provide a composition that can be easily incorporated into daily life and inhibits infection with COVID-19. [Solution] A composition according to the present invention contains inulin and inhibits infection with SARS-CoV-2.

Description

組成物、飲食品、医薬品及びイヌリンの使用Compositions, food and drink products, medicines, and use of inulin
　本発明は、組成物、飲食品、医薬品及びイヌリンの使用に関する。 The present invention relates to compositions, food and drink products, pharmaceuticals, and uses of inulin.
　２０１９年末に中国で初めて報告された新型コロナウイルス（ＳＡＲＳ－ＣｏＶ－２）は、ニドウイルス目コロナウイルス科に属するＲＮＡウイルスであり、世界的なパンデミックを引き起こしている。新型コロナウイルスによるコロナウイルス感染症（ＣＯＶＩＤ－１９）に罹患すると、発熱、呼吸困難等の急性呼吸器症状を伴い、悪化すると、肺炎を発症することが報告されている。 The new coronavirus (SARS-CoV-2), which was first reported in China at the end of 2019, is an RNA virus that belongs to the order Nidovirales and the family Coronaviridae, and has caused a global pandemic. It has been reported that those infected with coronavirus infection (COVID-19) caused by the new coronavirus are accompanied by acute respiratory symptoms such as fever and difficulty breathing, and if the symptoms worsen, pneumonia can develop.
　そこで、新型コロナウイルスによるコロナウイルス感染症の発生抑制のために、様々な方法が検討されている（例えば、特許文献１等）。 Therefore, various methods are being considered to suppress the outbreak of coronavirus infection caused by the new coronavirus (for example, Patent Document 1).
特開２０２２－８０６０号公報JP2022-8060A
　しかしながら、現状、新型コロナウイルスによるコロナウイルス感染症を抑制し得る組成物等については、十分には開発されておらず、有効性のある組成物等の開発が望まれている。また、当該組成物等については、日常的に容易に取り入れることが可能な形態であることが望ましい。 However, currently, compositions that can suppress coronavirus infections caused by the new coronavirus have not been sufficiently developed, and the development of effective compositions is desired. Further, it is desirable that the composition etc. be in a form that can be easily taken in on a daily basis.
　本発明は、日常的に容易に取り入れることが可能で、新型コロナウイルスの感染を抑制する組成物の提供を目的とする。 The present invention aims to provide a composition that can be easily taken on a daily basis and suppresses infection with the new coronavirus.
　上記課題を解決するための本発明の主たる発明は、
　イヌリンを含有し、ＳＡＲＳ－ＣｏＶ－２の感染を抑制する、組成物である。 The main invention of the present invention for solving the above problems is as follows:
A composition containing inulin and inhibiting SARS-CoV-2 infection.
　その他、本願が開示する課題やその解決方法については、発明の実施形態の欄及び図面により明らかにされる。 Other problems and solutions disclosed in the present application will be made clear by the embodiments section and the drawings.
　本発明によれば、日常的に容易に取り入れることが可能で、新型コロナウイルスの感染を抑制する組成物を提供することができる。 According to the present invention, it is possible to provide a composition that can be easily taken on a daily basis and suppresses infection with the new coronavirus.
本発明の実施例における生存曲線を示す図。The figure which shows the survival curve in the Example of this invention. （ａ）本発明の実施例における体温の変化を示す図。（ｂ）本発明の実施例における体重の変化を示す図。(a) A diagram showing changes in body temperature in an example of the present invention. (b) A diagram showing changes in body weight in Examples of the present invention. 本発明の実施例におけるコントロール群と試験群とで有意差があった細菌群示す図。FIG. 2 is a diagram showing bacterial groups that were significantly different between a control group and a test group in an example of the present invention. 本発明の実施例におけるコントロール群と試験群とで有意差があった細菌群示す図。FIG. 2 is a diagram showing bacterial groups that were significantly different between a control group and a test group in an example of the present invention. 本発明の実施例におけるコントロール群と試験群とで有意差があった細菌群示す図。FIG. 2 is a diagram showing bacterial groups that were significantly different between a control group and a test group in an example of the present invention. 本発明の実施例におけるコントロール群と試験群とで有意差があった細菌群示す図。FIG. 2 is a diagram showing bacterial groups that were significantly different between a control group and a test group in an example of the present invention. 本発明の実施例におけるコントロール群と試験群とで有意差があった細菌群示す図。FIG. 2 is a diagram showing bacterial groups that were significantly different between a control group and a test group in an example of the present invention. 本発明の実施例におけるコントロール群と試験群とで有意差は無いが占有率が高い細菌群を示す図。FIG. 2 is a diagram showing bacterial groups that have a high occupancy rate but are not significantly different between a control group and a test group in an example of the present invention. 本発明の実施例におけるコントロール群と試験群とで有意差は無いが占有率が高い細菌群を示す図。FIG. 2 is a diagram showing bacterial groups that have a high occupancy rate but are not significantly different between a control group and a test group in an example of the present invention. 本発明の実施例におけるコントロール群と試験群とで有意差は無いが占有率が高い細菌群を示す図。FIG. 2 is a diagram showing bacterial groups that have a high occupancy rate but are not significantly different between a control group and a test group in an example of the present invention. 本発明の実施例における代謝物質のうち短鎖脂肪酸の平均値を示す図。The figure which shows the average value of short chain fatty acids among the metabolites in the Example of this invention. 本発明の実施例における代謝物質のうち胆汁酸の平均値を示す図。The figure which shows the average value of bile acid among the metabolites in the Example of this invention. 本発明の実施例における代謝物質として短鎖脂肪酸を示す図。FIG. 2 is a diagram showing short chain fatty acids as metabolites in Examples of the present invention. 本発明の実施例における代謝物質として短鎖脂肪酸を示す図。FIG. 2 is a diagram showing short chain fatty acids as metabolites in Examples of the present invention. 本発明の実施例における代謝物質として短鎖脂肪酸を示す図。FIG. 2 is a diagram showing short chain fatty acids as metabolites in Examples of the present invention. 本発明の実施例における代謝物質として１次および２次胆汁酸を示す図。FIG. 2 is a diagram showing primary and secondary bile acids as metabolites in an example of the present invention. 本発明の実施例における代謝物質として抱合型胆汁酸を示す図。FIG. 2 is a diagram showing conjugated bile acids as metabolites in Examples of the present invention. 本発明の実施例における代謝物質として抱合型胆汁酸を示す図。FIG. 2 is a diagram showing conjugated bile acids as metabolites in Examples of the present invention. 本発明の実施例における代謝物質として抱合型胆汁酸を示す図。FIG. 2 is a diagram showing conjugated bile acids as metabolites in Examples of the present invention.
　以下に、組成物、飲食品、医薬品及びイヌリンの使用の実施形態を、図面に基づいて説明する。なお、本実施形態により本発明が限定されるものではない。 Below, embodiments of compositions, food and drink products, pharmaceuticals, and uses of inulin will be described based on the drawings. Note that the present invention is not limited to this embodiment.
　本発明は、例えば、以下のような構成を備える。
　［項目１］
　イヌリンを含有し、ＳＡＲＳ－ＣｏＶ－２の感染を抑制する、組成物。
　［項目２］
　前記イヌリンは、数平均分子量（Ｍｎ）が５００以上４０００以下である、項目１に記載の組成物。
　［項目３］
　前記イヌリンは、平均重合度（ＤＰ）が３以上３０以下である、項目１又は２に記載の組成物。
　［項目４］
　前記イヌリンは、平均鎖長が８以上１３以下である、項目１ないし３のいずれか一つに記載の組成物。
　［項目５］
　前記イヌリンは、酵素法により製造されていない、項目１ないし４のいずれか一つに記載の組成物。
　［項目６］
　前記イヌリンは、チコリの根由来である、項目１ないし５のいずれか一つに記載の組成物。
　［項目７］
　胆汁酸の分泌を増加させる、項目１ないし６のいずれか一つに記載の組成物。
　［項目８］
　胆汁酸の分泌の増加及び／又は減少によってＳＡＲＳ－ＣｏＶ－２の感染を抑制する、項目１ないし６のいずれか一つに記載の組成物。
　［項目９］
　前記胆汁酸の分泌の増加における前記胆汁酸が、リトコール酸（ＬＣＡ）、ウルソデオキシコール酸（ＵＤＣＡ）、デオキシコール酸（ＤＣＡ）、コール酸（ＣＡ）、グリコデオキシコール酸（ＧＤＣＡ）、タウロリトコール酸（ＴＬＣＡ）、タウロウルソデオキシコール酸（ＴＵＤＣＡ）、タウロデオキシコール酸（ＴＤＣＡ）及びタウロコール酸（ＴＣＡ）からなる群から選択される少なくとも一つであり、
　前記胆汁酸の分泌の減少における前記胆汁酸が、グリコウルソデオキシコール酸（ＧＵＤＣＡ）、グリココール酸（ＧＣＡ）及びタウロケノデオキシコール酸（ＴＣＤＣＡ）からなる群から選択される少なくとも一つである、項目８に記載の組成物。
　［項目１０］
　前記胆汁酸の分泌の増加における前記胆汁酸が、コール酸（ＣＡ）、デオキシコール酸（ＤＣＡ）及びリトコール酸（ＬＣＡ）からなる群から選択される少なくとも一つである、項目９に記載の組成物。
　［項目１１］
　Ｔｒｅｐｏｎｅｍａ　２、Ｐａｒａｂａｃｔｅｒｏｉｄｅｓ、Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ及びＡ２からなる群から選択される少なくとも一つの菌の増加及び／又はＥｉｓｅｎｂｅｒｇｉｅｌｌａ、Ｒｕｍｉｎｉｃｌｏｓｔｒｉｄｉｕｍ　５、Ｃｏｐｒｏｓｔａｎｏｌｉｇｅｎｅｓ　ｇｒｏｕｐ、Ｒｕｍｉｎｉｃｌｏｓｔｒｉｄｉｕｍ　１、Ｌａｃｔｏｃｏｃｃｕｓ、Ａｎａｅｒｏｐｌａｓｍａ、Ｂｕｔｙｒｉｃｉｍｏｎａｓ、Ｔｙｚｚｅｒｅｌｌａ及びＰｙｇｍａｉｏｂａｃｔｅｒからなる群から選択される少なくとも一つの菌の減少によってＳＡＲＳ－ＣｏＶ－２の感染を抑制する、項目１ないし１０のいずれか一つに記載の組成物。
　［項目１２］
　項目１ないし１１のいずれか一つに記載の組成物を含有し、ＳＡＲＳ－ＣｏＶ－２の感染を抑制する、飲食品。
　［項目１３］
　項目１ないし１１のいずれか一つに記載の組成物を含有し、ＳＡＲＳ－ＣｏＶ－２の感染を抑制する、医薬品。
　［項目１４］
　胆汁酸の分泌増加のための、イヌリンの使用。
　［項目１５］
　ＳＡＲＳ－ＣｏＶ－２の感染抑制のための、イヌリンの使用。 The present invention includes, for example, the following configuration.
[Item 1]
A composition containing inulin and inhibiting SARS-CoV-2 infection.
[Item 2]
The composition according to item 1, wherein the inulin has a number average molecular weight (Mn) of 500 or more and 4000 or less.
[Item 3]
The composition according to item 1 or 2, wherein the inulin has an average degree of polymerization (DP) of 3 or more and 30 or less.
[Item 4]
The composition according to any one of items 1 to 3, wherein the inulin has an average chain length of 8 or more and 13 or less.
[Item 5]
5. The composition according to any one of items 1 to 4, wherein the inulin is not produced by an enzymatic method.
[Item 6]
6. The composition according to any one of items 1 to 5, wherein the inulin is derived from chicory root.
[Item 7]
7. The composition according to any one of items 1 to 6, which increases the secretion of bile acids.
[Item 8]
7. The composition according to any one of items 1 to 6, which inhibits SARS-CoV-2 infection by increasing and/or decreasing bile acid secretion.
[Item 9]
The bile acids in the increase in bile acid secretion include lithocholic acid (LCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), cholic acid (CA), glycodeoxycholic acid (GDCA), taurolithochol at least one selected from the group consisting of acid (TLCA), tauroursodeoxycholic acid (TUDCA), taurodeoxycholic acid (TDCA), and taurocholic acid (TCA),
Item 8, wherein the bile acid in the reduction of bile acid secretion is at least one selected from the group consisting of glycoursodeoxycholic acid (GUDCA), glycocholic acid (GCA), and taurochenodeoxycholic acid (TCDCA). The composition described in .
[Item 10]
The composition according to item 9, wherein the bile acid in increasing secretion of bile acids is at least one selected from the group consisting of cholic acid (CA), deoxycholic acid (DCA), and lithocholic acid (LCA). thing.
[Item 11]
Increase in at least one bacterium selected from the group consisting of Treponema 2, Parabacteroides, Bifidobacterium and A2 and/or Eisenbergiella, Ruminiclostridium 5, Coprostanoligenes group, R uminiclostridium 1, Lactococcus, Anaeroplasma, Butyricimonas, Tyzzerella and Pygmaiobacter. 11. The composition according to any one of items 1 to 10, which suppresses SARS-CoV-2 infection by reducing at least one bacterium.
[Item 12]
A food or drink containing the composition according to any one of items 1 to 11, which suppresses SARS-CoV-2 infection.
[Item 13]
A pharmaceutical product containing the composition according to any one of items 1 to 11, which suppresses SARS-CoV-2 infection.
[Item 14]
Use of inulin to increase bile acid secretion.
[Item 15]
Use of inulin to inhibit SARS-CoV-2 infection.
　＜定義＞
　本明細書において、新型コロナウイルス（ＳＡＲＳ－ＣｏＶ－２）により引き起こされる感染症が、新型コロナウイルス感染症（ＣＯＶＩＤ－１９）である。ここで、新型コロナウイルスには、従来株のみでなく、変異株も含まれる。かかる変異株としては、例えば、Ｎ５０１Ｙの変異がある変異株としては、英国で確認された変異株（ＶＯＣ－２０２０１２／０１）、南アフリカで確認された変異株（５０１Ｙ．Ｖ２）、ブラジルで確認された変異株（５０１Ｙ．Ｖ３）等が挙げられ、「Ｅ４８４Ｋの変異がある変異株」としては、南アフリカで確認された変異株（５０１Ｙ．Ｖ２）、ブラジルで確認された変異株（５０１Ｙ．Ｖ３）等が挙げられるが、これらに限定はされない。 <Definition>
In this specification, the infectious disease caused by the new coronavirus (SARS-CoV-2) is the new coronavirus infection (COVID-19). Here, the new coronavirus includes not only conventional strains but also mutant strains. Such mutant strains include, for example, mutant strains with the N501Y mutation, such as the mutant strain confirmed in the UK (VOC-202012/01), the mutant strain confirmed in South Africa (501Y.V2), and the variant strain confirmed in Brazil. Examples of the "mutant strain with the E484K mutation" include the mutant strain confirmed in South Africa (501Y.V2) and the mutant strain confirmed in Brazil (501Y.V3). etc., but are not limited to these.
　「感染抑制」とは、新型コロナウイルス感染症（ＣＯＶＩＤ－１９）の治療または予防の概念を含み、新型コロナウイルス（ＳＡＲＳ－ＣｏＶ－２）が体内に侵入することを阻害又は遅延させること、新型コロナウイルス（ＳＡＲＳ－ＣｏＶ－２）の体外への排出を促進することなども含まれる。 "Infection control" includes the concept of treatment or prevention of the new coronavirus infection (COVID-19), including the concept of inhibiting or delaying the entry of the new coronavirus (SARS-CoV-2) into the body, This includes promoting the elimination of coronavirus (SARS-CoV-2) from the body.
　本明細書において、「治療」とは、新型コロナウイルスに感染することに起因して生じる１以上の症状を軽減又は改善すること、重症化を抑制すること、及びその疾患の進行を遅延させることを意味する。「予防」とは、新型コロナウイルス感染症の発症の阻害、発症リスクの低減又は発症の遅延などを意味する。また、無症状のコロナウイルス保持者（症状はないがＰＣＲ（ポリメラーゼ連鎖反応）検査などでコロナウイルス陽性が確認された者）に、発症の阻害、他者への感染リスク低減などを目的にイヌリンを投与することも、治療又は予防に含まれる。 As used herein, "treatment" refers to reducing or improving one or more symptoms caused by infection with the new coronavirus, suppressing the severity of the disease, and delaying the progression of the disease. means. "Prevention" means inhibiting the onset of the new coronavirus infection, reducing the risk of onset, or delaying the onset of the disease. In addition, we are administering inulin to asymptomatic coronavirus carriers (those who have no symptoms but have been confirmed positive for coronavirus through PCR (polymerase chain reaction) tests, etc.) to prevent the onset of symptoms and reduce the risk of infection to others. Treatment or prevention also includes administering.
　本明細書において、「イヌリン」とは、キク科やアヤメ科などの種々の植物に含まれる水溶性食物繊維に分類されている多糖類の一つであり、グルコースにフルクトースが複数個結合した重合体である。詳細には、イヌリンは、末端にグルコースをもつフルクトースの多糖ポリマーである、水溶性食物繊維として知られているフルクタンのうち、Ｄ－フルクトフラノースがβ２→１グリコシド結合で重合した直鎖状フルクタンである「直鎖イヌリン」を含む。また、本明細書において、「イヌリン」は、β２→１グリコシド結合及び少なくとも１つのβ２→６グリコシド結合を有する分岐状フルクタンである「分岐鎖イヌリン」も含むことができる。 In this specification, "inulin" is a polysaccharide classified as a water-soluble dietary fiber contained in various plants such as Asteraceae and Iridaceae, and is a polysaccharide in which multiple fructose molecules are bonded to glucose. It is a combination. Specifically, inulin is a linear fructan in which D-fructofuranose is polymerized with β2→1 glycosidic bonds among fructans known as water-soluble dietary fibers, which are polysaccharide polymers of fructose with glucose at the end. Contains "linear inulin", which is In addition, as used herein, "inulin" can also include "branched inulin", which is a branched fructan having a β2→1 glycosidic bond and at least one β2→6 glycosidic bond.
　本明細書において、「平均重合度」とは、イヌリン中のサッカライド単位（フルクトース及びグルコース単位）の数の平均値をいう。 As used herein, "average degree of polymerization" refers to the average number of saccharide units (fructose and glucose units) in inulin.
　＜組成物＞
　本実施形態に係る組成物は、イヌリンを含有し、ＳＡＲＳ－ＣｏＶ－２の感染を抑制するものである。イヌリンは、腸内において特定の菌数を増加及び／又は減少させること、当該細菌が産生する代謝物質（例えば短鎖脂肪酸や二次胆汁酸など）を増加及び／又は減少させること、これらの変化を介して宿主から分泌される代謝物質（例えば胆汁酸）を増加及び／又は減少させることなどにより、ＳＡＲＳ－ＣｏＶ－２の感染を抑制すると考えられる。腸内細菌が産生する短鎖脂肪酸は、大腸のリンパ濾胞において免疫細胞に作用し、大腸内での免疫グロブリンＡ（ＩｇＡ）産生を増強することが知られている。また、大腸から吸収されて血中に移行した短鎖脂肪酸は小腸パイエル板の免疫細胞にも作用し、小腸でのＩｇＡ産生も増強することが知られている。ＩｇＡの分泌量が増えることは、ＳＡＲＳ－ＣｏＶ－２感染症をはじめとする様々な感染症の予防に貢献すると考えられる。また、二次胆汁酸の１種であるウルソデオキシコール酸は、ＳＡＲＳ－ＣｏＶ－２が感染時に最初に結合する受容体であるアンジオテンシン変換酵素２（ＡＣＥ２）と、ＳＡＲＳ－ＣｏＶ－２との結合を阻害することが知られている。そのため、胆汁酸の分泌促進や、腸内細菌の働きである二次胆汁酸の産生が活性化されることにより、ＳＡＲＳ－ＣｏＶ－２感染症を予防することができると考えられる。本実施形態に係るイヌリンを含有する組成物により、日常的に容易に取り入れることが可能で、新型コロナウイルスの感染を抑制する方法を提供することができる。 <Composition>
The composition according to this embodiment contains inulin and suppresses SARS-CoV-2 infection. Inulin increases and/or decreases the number of specific bacteria in the intestines, increases and/or decreases metabolites produced by the bacteria (e.g. short chain fatty acids and secondary bile acids), and changes in these. It is thought that infection with SARS-CoV-2 is suppressed by increasing and/or decreasing metabolites (eg, bile acids) secreted from the host via . It is known that short chain fatty acids produced by intestinal bacteria act on immune cells in the lymphoid follicles of the large intestine and enhance immunoglobulin A (IgA) production in the large intestine. Furthermore, it is known that short chain fatty acids absorbed from the large intestine and transferred to the blood also act on immune cells in Peyer's patches in the small intestine and enhance IgA production in the small intestine. An increase in the amount of IgA secreted is thought to contribute to the prevention of various infectious diseases including SARS-CoV-2 infection. In addition, ursodeoxycholic acid, a type of secondary bile acid, binds to angiotensin-converting enzyme 2 (ACE2), which is the first receptor that SARS-CoV-2 binds to during infection, and SARS-CoV-2. is known to inhibit Therefore, it is thought that SARS-CoV-2 infection can be prevented by promoting the secretion of bile acids and activating the production of secondary bile acids, which is the function of intestinal bacteria. The composition containing inulin according to the present embodiment can be easily taken on a daily basis and can provide a method for suppressing infection with the new coronavirus.
　本実施形態に係る組成物に含まれるイヌリンは、数平均分子量（Ｍｎ）が５００以上７０００以下であることができ、５００以上４０００以下であることができ、任意の数平均分子量のみを含有するものとすることができる。イヌリンの平均分子量は、ＧＰＣクロマトグラフィーを用いて既知標準品プルランとの比較から求める方法により、測定することができる。なお、イヌリンの数平均分子量を所望の値に調整する方法としては、通常この分野で行われている方法であればいずれを用いてもよく、例えば、抽出したイヌリン自体を分離する方法、抽出したイヌリン自体を分解する方法等が挙げられる。 The inulin contained in the composition according to the present embodiment may have a number average molecular weight (Mn) of 500 or more and 7,000 or less, and may have a number average molecular weight of 500 or more and 4,000 or less, and contains only an arbitrary number average molecular weight. It can be done. The average molecular weight of inulin can be determined by comparing it with a known standard pullulan using GPC chromatography. In addition, as a method for adjusting the number average molecular weight of inulin to a desired value, any method that is normally used in this field may be used. For example, a method of separating extracted inulin itself, a method of separating extracted inulin, Examples include a method of decomposing inulin itself.
　本実施形態において、イヌリンは、平均重合度（ＤＰ）が２以上１００以下の範囲であることができ、２以上６０以下であることができ、３以上３０以下であることができる。イヌリンの平均重合度は、例えば、液体クロマトグラフィー、ガスクロマトグラフィー、陰イオンクロマトグラフィー等の通常の分析法によって求めた分析結果のピークのトップを平均重合度とすることができる。なお、イヌリンの平均重合度を所望の値に調整する方法としては、通常この分野で行われている方法であればいずれを用いてもよく、具体的な方法としては、イヌリンの数平均分子量を調整する方法と同じものが挙げられる。 In the present embodiment, inulin can have an average degree of polymerization (DP) in a range of 2 or more and 100 or less, 2 or more and 60 or less, and 3 or more and 30 or less. The average degree of polymerization of inulin can be determined by, for example, the top of the peak in the analysis result obtained by a conventional analysis method such as liquid chromatography, gas chromatography, anion chromatography, or the like. Note that as a method for adjusting the average degree of polymerization of inulin to a desired value, any method that is normally used in this field may be used. The same method as the adjustment method can be mentioned.
　本実施形態において、イヌリンは直鎖であってもよく分岐鎖を有するものであることができ、修飾されたものであることができる。 In this embodiment, inulin may be linear, branched, or modified.
　直鎖イヌリンは、通常、平均鎖長が２以上１００以下の範囲であることができ、２以上６０以下の範囲であることができ、５以上３０以下であることができ、８以上１３以下であることができる。かかる直鎖イヌリンは、チコリの根由来のイヌリンの場合は、例えば、Ｉｎｕｌｉａ（登録商標）、Ｆｒｕｔａｆｉｔ（登録商標）、Ｒａｆｔｉｌｉｎｅ（登録商標）を用いることができ、酵素合成によるイヌリンを用いる場合には、例えば、フジＦＦ（登録商標）を用いることができる。 Normally, the average chain length of linear inulin can be in the range of 2 or more and 100 or less, it can be in the range of 2 or more and 60 or less, it can be 5 or more and 30 or less, and it can be 8 or more and 13 or less. Something can happen. Such linear inulin can be, for example, Inulia (registered trademark), Frutafit (registered trademark), or Raftiline (registered trademark) in the case of inulin derived from chicory root, and in the case of using inulin produced by enzymatic synthesis. For example, Fuji FF (registered trademark) can be used.
　分岐鎖イヌリンは、テキーラの原料である多肉質の植物であるアガベ（リュウゼツラン）に豊富に含まれることが知られている（J. Agric. Food Chem., (2003) 51 (27), pp 7835-7840、J. Agric. Food Chem., (2006) 54 (20), pp 7832-7839、等）。本発明における分岐鎖イヌリンは、特に限定されないが、例えば、上記アガベから国際公開０７／１４２３０６号パンフレット等に記載の常法により得られ、典型的には、アガベの茎部分であるピーニャから細断、搾汁、濾過、精製、濃縮、粉末乾燥等を行った処理物に含まれる。このような処理物はアガベイヌリンとも称される。 Branched-chain inulin is known to be abundant in agave, a succulent plant that is the raw material for tequila (J. Agric. Food Chem., (2003) 51 (27), pp 7835 -7840, J. Agric. Food Chem., (2006) 54 (20), pp 7832-7839, etc.). The branched chain inulin in the present invention is not particularly limited, but can be obtained, for example, from the agave by the conventional method described in WO 07/142306 pamphlet, etc., and is typically shredded from piña, which is the stem part of the agave. , included in processed products that have undergone juice extraction, filtration, purification, concentration, powder drying, etc. Such a processed product is also called agaba inulin.
　本実施形態において、イヌリンは、イヌリンを豊富に含む植物から当業者に周知の方法により採取したものを使用しても構わない。植物としては、例えば、チコリ、キクイモ、ダリア、ニンニク、ニラ、タマネギ、タンポポ、ゴボウを挙げることができる。また、イヌリンはチコリの根を酵素法により分解したものやサトウキビから酵素法により合成したもの、あるいはチコリの根を酵素法を用いずに製造したものなど、食品として使用できる範囲内で処理を加えたものを使用することができる。 In this embodiment, inulin may be collected from a plant rich in inulin by a method well known to those skilled in the art. Examples of plants include chicory, Jerusalem artichoke, dahlia, garlic, chive, onion, dandelion, and burdock. Additionally, inulin can be produced by decomposing chicory root using an enzymatic method, synthesizing it from sugarcane using an enzymatic method, or producing chicory root without using an enzymatic method, which has been processed to the extent that it can be used as a food. You can use the
　本実施形態に係る組成物の形態としては、イヌリンのみからなるもののほか、医薬品や食品添加剤、サプリメントなどの形態を挙げることができる。医薬品や食品添加剤、サプリメントの形態とする場合、その剤型としては、例えば、散剤、錠剤、糖衣剤、カプセル剤、顆粒剤、ドライシロップ剤、液剤、シロップ剤、ドロップ剤、ドリンク剤等の固形または液状の剤型を挙げることができる。 Examples of the form of the composition according to this embodiment include those consisting only of inulin, as well as forms such as pharmaceuticals, food additives, and supplements. In the case of pharmaceuticals, food additives, and supplements, the dosage forms include solid forms such as powders, tablets, sugar-coated agents, capsules, granules, dry syrups, liquids, syrups, drops, and drinks. Alternatively, a liquid dosage form can be mentioned.
　本実施形態に係る組成物は、イヌリンのみからなるもののほか、菓子や飲料、加工食品、健康食品、乳幼児食品などの通常の飲食物の形態を挙げることができる。飲食物の形態とする場合は、通常の製造過程で、有効成分を添加して製造することができる。イヌリンの甘味度は２０程度であり、その味質・物性・加工性はショ糖に近いことから、各種飲食物の製造過程において、砂糖の一部または全部をイヌリンに置き換えるなどして、砂糖と同様に扱って各種飲食物を製造することができる摂取量は任意の量、任意の摂取期間とすることができる。イヌリンの食品組成物又は飲料組成物への配合量としては特に制限はなく、食品組成物又は飲料組成物基準で、０．１重量％以上１０重量％以下であることができ、１重量％以上５重量％以下であることができる。 The composition according to the present embodiment can be in the form of ordinary food and drink such as confectionery, beverages, processed foods, health foods, and infant foods, in addition to those consisting only of inulin. When it is in the form of a food or drink, it can be manufactured by adding active ingredients in a normal manufacturing process. Inulin has a sweetness level of about 20, and its taste, physical properties, and processability are similar to sucrose, so inulin is used to replace part or all of sugar in the manufacturing process of various foods and drinks. The amount of intake that can be handled in the same manner to produce various foods and drinks can be any amount and any period of intake. There is no particular restriction on the amount of inulin added to the food composition or beverage composition, and it can be 0.1% by weight or more and 10% by weight or less, and 1% by weight or more, based on the food composition or beverage composition. It can be up to 5% by weight.
　本実施形態に係る組成物をヒトや動物に対して用いる場合の摂取又は投与量は、例えば、１日あたり０．０１５ｇ／ｋｇ体重以上を挙げることができる。係る摂取量は、１日１回に限らず、複数回に分割して摂取してもよい。摂取量は任意の量、任意の摂取期間とすることができる。これにより、本実施形態に係る組成物を、ＳＡＲＳ－ＣｏＶ－２の感染を抑制するために使用することができる。 When the composition according to the present embodiment is used for humans or animals, the intake or administration amount can be, for example, 0.015 g/kg or more per day. The intake amount is not limited to once a day, but may be divided into multiple doses. The amount of intake can be any amount and any period of intake. Thereby, the composition according to this embodiment can be used to suppress SARS-CoV-2 infection.
　本実施形態において、イヌリンを含有する組成物を摂取することにより分泌が増加する胆汁酸は、リトコール酸（ＬＣＡ）、ウルソデオキシコール酸（ＵＤＣＡ）、デオキシコール酸（ＤＣＡ）、コール酸（ＣＡ）、グリコデオキシコール酸（ＧＤＣＡ）、タウロリトコール酸（ＴＬＣＡ）、タウロウルソデオキシコール酸（ＴＵＤＣＡ）、タウロデオキシコール酸（ＴＤＣＡ）及びタウロコール酸（ＴＣＡ）からなる群から選択される少なくとも一つであり、分泌が減少する胆汁酸は、グリコウルソデオキシコール酸（ＧＵＤＣＡ）、グリココール酸（ＧＣＡ）及びタウロケノデオキシコール酸（ＴＣＤＣＡ）からなる群から選択される少なくとも一つであることができる。 In this embodiment, the bile acids whose secretion is increased by ingesting a composition containing inulin are lithocholic acid (LCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), and cholic acid (CA). , glycodeoxycholic acid (GDCA), taurolithocholic acid (TLCA), tauroursodeoxycholic acid (TUDCA), taurodeoxycholic acid (TDCA), and taurocholic acid (TCA). The bile acid whose secretion is decreased may be at least one selected from the group consisting of glycoursodeoxycholic acid (GUDCA), glycocholic acid (GCA), and taurochenodeoxycholic acid (TCDCA).
　本実施形態において、イヌリンを含有する組成物を摂取することにより増加する菌は、Ｔｒｅｐｏｎｅｍａ　２、Ｐａｒａｂａｃｔｅｒｏｉｄｅｓ、Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ及びＡ２からなる群から選択される少なくとも一つの菌であり、減少する菌は、Ｅｉｓｅｎｂｅｒｇｉｅｌｌａ、Ｒｕｍｉｎｉｃｌｏｓｔｒｉｄｉｕｍ　５、Ｃｏｐｒｏｓｔａｎｏｌｉｇｅｎｅｓ　ｇｒｏｕｐ、Ｒｕｍｉｎｉｃｌｏｓｔｒｉｄｉｕｍ　１、Ｌａｃｔｏｃｏｃｃｕｓ、Ａｎａｅｒｏｐｌａｓｍａ、Ｂｕｔｙｒｉｃｉｍｏｎａｓ、Ｔｙｚｚｅｒｅｌｌａ及びＰｙｇｍａｉｏｂａｃｔｅｒからなる群から選択される少なくとも一つの菌であることができる。 In this embodiment, the bacteria that increase by ingesting the composition containing inulin are at least one bacteria selected from the group consisting of Treponema 2, Parabacteroides, Bifidobacterium, and A2, and the bacteria that decrease are Eisenbergiella, Ruminiclostridium 5, Coprostanoligenes group, Ruminiclostridium 1, Lactococcus, Anaeroplasma, Butyricimonas, Tyzzerel The microorganism may be at least one bacterium selected from the group consisting of P. la and Pygmaiobacter.
　次に実施例を示して本発明をさらに詳細に説明するが、本発明は以下の実施例に限定されるものではない。 Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to the following Examples.
　１．実験方法
　日本ＳＬＣ株式会社より購入した４週齢メスのシリアンハムスターを１１～１２匹ずつコントロール群（ＡＩＮ－９３Ｇ飼料）と試験群（ＡＩＮ－９３Ｇ飼料＋５％イヌリン食）とに分け、ＳＰＦ（Ｓｐｅｃｉｆｉｃ　Ｐａｔｈｏｇｅｎ　Ｆｒｅｅ）条件下、食餌自由摂食、自由飲水を可能にし、１２時間の明／暗サイクルで２週間飼育した。イヌリンとして、チコリの根から抽出・精製したイヌリン（Ｉｎｕｌｉａ（登録商標）ＩＱ（帝人株式会社））を使用した。 1. Experimental method 11 to 12 4-week-old female Syrian hamsters purchased from Japan SLC Co., Ltd. were divided into a control group (AIN-93G feed) and a test group (AIN-93G feed + 5% inulin diet). The mice were reared for 2 weeks under 12-hour light/dark cycle with free access to food and water under (pathogen-free) conditions. Inulin extracted and purified from chicory root (Inulia (registered trademark) IQ (Teijin Ltd.)) was used as inulin.
　その後、ＳＡＲＳ－ＣｏＶ－２／ＵＴ－ＮＣＧＭ０２／Ｈｕｍａｎ／２０２０／Ｔｏｋｙｏを、鼻腔内経路から感染させた。ウイルスの感染は、シリアンハムスターを、ペントバルビタールナトリウムの腹腔内注射による完全麻酔下で、２×１０６　ｐｆｕのＳＡＲＳ－ＣｏＶ－２を鼻腔内に適用することにより行った（感染させた日をＤａｙ　０とする）。これらのシリアンハムスターを、ウイルス感染前と同一の条件下で１４日間飼育し、生存および死亡を確認した。 Thereafter, SARS-CoV-2/UT-NCGM02/Human/2020/Tokyo was infected via the intranasal route. Viral infection was performed by intranasally applying 2×10 6 pfu of SARS-CoV-2 to Syrian hamsters under complete anesthesia with intraperitoneal injection of pentobarbital sodium (day of infection was determined). 0). These Syrian hamsters were raised for 14 days under the same conditions as before virus infection, and survival and death were confirmed.
　また、イヌリン摂取による腸内環境の変化がＳＡＲＳ－ＣｏＶ－２感染防御に寄与するか否かを調べるために、コントロール食または試験食１４日間の便中細菌叢と、コントロール食または試験食１４日間の便中短鎖脂肪酸および胆汁酸量を調べた。検定方法としてマンホイットニーのＵ検定を用いた。 In addition, in order to investigate whether changes in the intestinal environment due to inulin intake contribute to protection against SARS-CoV-2 infection, we investigated the fecal microbiota after 14 days of the control diet or test diet, and the fecal microbiota after 14 days of the control diet or test diet. The amounts of short-chain fatty acids and bile acids in the stool of the subjects were investigated. The Mann-Whitney U test was used as a testing method.
　便中細菌叢の系統組成を明らかにするため、１６Ｓ　ｒＲＮＡ遺伝子配列を用いたメタゲノム解析を行った。まず便から抽出したＤＮＡを鋳型として、１６Ｓ　ｒＲＮＡ遺伝子のＶ１－Ｖ２領域のＤＮＡ断片をＰＣＲにて増幅し、続いてＰＣＲ産物の配列をＩｌｌｕｍｉｎａ　ＭｉＳｅｑを用いたペアエンド法により解析した。これらの塩基配列をｂｏｗｔｉｅ２により１６Ｓ　ｒＲＮＡ遺伝子のデータベースに対してマッピングした。１６Ｓ　ｒＲＮＡ遺伝子のデータベースには、ｓｉｌｖａが提供するＳＩＬＶＡ　ＳＳＵ　Ｒｅｆを９９％の閾値でクラスタリングして得られたＯＴＵを用いた（以下、ＳＩＬＶＡデータベースと記載）。上記マッピングにより、各塩基配列はＳＩＬＶＡデータベース内で最も類似しているＯＴＵに帰属され、各ＯＴＵに帰属した（マップされた）塩基配列数を数えることで、腸内細菌叢の細菌系統組成を定量化した。 In order to clarify the phylogenetic composition of the fecal microbiota, metagenomic analysis using 16S rRNA gene sequences was performed. First, a DNA fragment of the V1-V2 region of the 16S rRNA gene was amplified by PCR using DNA extracted from stool as a template, and then the sequence of the PCR product was analyzed by the paired-end method using Illumina MiSeq. These nucleotide sequences were mapped against the 16S rRNA gene database using bowtie2. For the 16S rRNA gene database, OTUs obtained by clustering SILVA SSU Ref provided by silva using a 99% threshold were used (hereinafter referred to as the SILVA database). Through the above mapping, each base sequence is assigned to the most similar OTU in the SILVA database, and by counting the number of base sequences assigned (mapped) to each OTU, the bacterial phylogenetic composition of the intestinal flora can be quantified. It became.
　次に、便中短鎖脂肪酸および胆汁酸量を評価するため、便中代謝物質の定量評価を実施した。まず、有機溶媒を用いた液液抽出により便から代謝物質を抽出し、短鎖脂肪酸測定用サンプルと、胆汁酸測定用サンプルに分割した。短鎖脂肪酸測定用サンプルには誘導体化処理を施した後、胆汁酸測定用サンプルにはそのまま、溶出時間補正用の内部標準物質を添加した。短鎖脂肪酸はＧＣ－ＭＳ、胆汁酸はＬＣ－ＴＯＦ／ＭＳを用いて測定した。代謝物質はＬＣ－ＴＯＦ／ＭＳを用いて測定し、検出されたピークのカラム保持時間、質量電荷比（ｍ／ｚ）、ピーク面積を取得した。これらの情報を標準試料の測定結果と照合することで各ピークが対応する代謝物質を同定した。これらのピークは、検体ごとに内部標準物質との面積比が一定になるように補正し、サンプル間で相対定量が可能な値（相対面積比）に変換した。代謝物質のうち有機酸・短鎖脂肪酸分析では９化合物、胆汁酸分析では１４化合物を濃度既知の標準試料を用いて作成した検量線と比較することにより、絶対定量を行った。 Next, in order to evaluate the amount of short-chain fatty acids and bile acids in the stool, quantitative evaluation of metabolites in the stool was performed. First, metabolites were extracted from stool by liquid-liquid extraction using an organic solvent and divided into a sample for short-chain fatty acid measurement and a sample for bile acid measurement. After derivatizing the short-chain fatty acid measurement sample, an internal standard substance for elution time correction was directly added to the bile acid measurement sample. Short chain fatty acids were measured using GC-MS, and bile acids were measured using LC-TOF/MS. Metabolites were measured using LC-TOF/MS, and the column retention time, mass-to-charge ratio (m/z), and peak area of the detected peaks were obtained. By comparing this information with the measurement results of standard samples, we identified the metabolites to which each peak corresponds. These peaks were corrected so that the area ratio with the internal standard substance was constant for each sample, and converted into a value (relative area ratio) that allows relative quantification between samples. Of the metabolites, 9 compounds were analyzed for organic acids and short chain fatty acids, and 14 compounds were analyzed for bile acids, and absolute quantification was performed by comparing them with calibration curves prepared using standard samples with known concentrations.
　２．実験結果
　図１に生存曲線を示す。コントロール群に対し、イヌリン食を摂取したハムスターは有意に生存率が延長した。また、図２（ａ）に示すように、イヌリン摂取群ではコントロール群と比較して感染後７日間に渡り有意に体温が高かった。また、図２（ｂ）に示すように、イヌリン摂取群ではコントロール群と比較して感染４日後から６日後にかけて体重減少が有意に抑制された。 2. Experimental Results Figure 1 shows the survival curve. Compared to the control group, hamsters receiving an inulin diet had a significantly longer survival rate. Furthermore, as shown in FIG. 2(a), body temperature was significantly higher in the inulin intake group over 7 days after infection compared to the control group. Furthermore, as shown in FIG. 2(b), weight loss was significantly suppressed in the inulin intake group from 4 days to 6 days after infection compared to the control group.
　図３～図７にコントロール群とイヌリン摂取群とで有意差があった細菌群を、図８～図１０にコントロール群とイヌリン摂取群とで有意差は無いが、占有率が高い細菌群を示す。これらの結果より、コントロール群と比較して、試験群では、Ｔｒｅｐｏｎｅｍａ　２、Ｐａｒａｂａｃｔｅｒｏｉｄｅｓ、Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ、Ａ２が有意に増加し、Ｅｉｓｅｎｂｅｒｇｉｅｌｌａ、Ｒｕｍｉｎｉｃｌｏｓｔｒｉｄｉｕｍ　５、Ｃｏｐｒｏｓｔａｎｏｌｉｇｅｎｅｓ　ｇｒｏｕｐ、Ｒｕｍｉｎｉｃｌｏｓｔｒｉｄｉｕｍ　１、Ｌａｃｔｏｃｏｃｃｕｓ、Ａｎａｅｒｏｐｌａｓｍａ、Ｂｕｔｙｒｉｃｉｍｏｎａｓ、Ｔｙｚｚｅｒｅｌｌａ、Ｐｙｇｍａｉｏｂａｃｔｅｒが有意に減少した。なお、上記有意差については、通常この分野で行われているマンホイットニーのＵ検定により、Ｐ値が０．０５未満（Ｐ＜０．０５）であるものを有意差ありと判定した。 Figures 3 to 7 show bacterial groups with significant differences between the control group and inulin intake group, and Figures 8 to 10 show bacterial groups with high occupancy rates but no significant differences between the control group and inulin intake group. show. From these results, compared to the control group, Treponema 2, Parabacteroides, Bifidobacterium, and A2 significantly increased in the test group, and Eisenbergiella, Ruminiclostridium 5, and Coprostanoligene. s group, Ruminiclostridium 1, Lactococcus, Anaeroplasma, Butyricimonas, Tyzzerella, Pygmaiobacter decreased significantly. Regarding the above-mentioned significant difference, a P value of less than 0.05 (P<0.05) was determined to be significant using Mann-Whitney U test, which is commonly performed in this field.
　図１１に代謝物質のうち短鎖脂肪酸の平均値を、図１２に代謝物質のうち胆汁酸の平均値を示す。また、図１３～図１５に代謝物質として短鎖脂肪酸を、図１６に代謝物質として１次および２次胆汁酸を、図１７～図１９に代謝物質として抱合型胆汁酸を示す。これらの結果より、コントロール群と比較して、試験群では、リトコール酸（ＬＣＡ）、ウルソデオキシコール酸（ＵＤＣＡ）、デオキシコール酸（ＤＣＡ）、コール酸（ＣＡ）、グリコデオキシコール酸（ＧＤＣＡ）、タウロリトコール酸（ＴＬＣＡ）、タウロウルソデオキシコール酸（ＴＵＤＣＡ）、タウロデオキシコール酸（ＴＤＣＡ）、タウロコール酸（ＴＣＡ）の分泌が有意に増加し、グリコウルソデオキシコール酸（ＧＵＤＣＡ）、グリココール酸（ＧＣＡ）、タウロケノデオキシコール酸（ＴＣＤＣＡ）の分泌が有意に減少した。 Figure 11 shows the average value of short chain fatty acids among metabolites, and Figure 12 shows the average value of bile acids among metabolites. Furthermore, FIGS. 13 to 15 show short chain fatty acids as metabolites, FIG. 16 shows primary and secondary bile acids as metabolites, and FIGS. 17 to 19 show conjugated bile acids as metabolites. From these results, compared to the control group, the test group had lower levels of lithocholic acid (LCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), cholic acid (CA), and glycodeoxycholic acid (GDCA). , taurolithocholic acid (TLCA), tauroursodeoxycholic acid (TUDCA), taurodeoxycholic acid (TDCA), taurocholic acid (TCA) secretion was significantly increased, and glycoursodeoxycholic acid (GUDCA), glycocholic acid (GCA) and taurochenodeoxycholic acid (TCDCA) secretion was significantly decreased.
　以上により、５％イヌリン摂取群ではＳＡＲＳ－ＣｏＶ－２感染の有意な抑制効果が認められ、便中細菌叢として、複数の細菌群に変動が認められた。また、便中の乳酸が増加し、酪酸も増加傾向であり、便中１次および２次胆汁酸に有意な増加が認められた。これらの結果により、イヌリンは腸内細菌のバランスや腸内細菌の代謝を変化させ、さらに／あるいは宿主の胆汁酸の分泌を増加及び／又は減少させ、これによってＳＡＲＳ－ＣｏＶ－２の感染を抑制する。そのため、イヌリンの摂取は日常的に容易に取り入れることが可能で、新型コロナウイルスの感染を抑制することが可能な手法であることが示唆された。 From the above, a significant suppressive effect on SARS-CoV-2 infection was observed in the 5% inulin intake group, and changes were observed in multiple bacterial groups in the fecal flora. Furthermore, lactic acid in the stool increased, butyric acid also tended to increase, and a significant increase was observed in primary and secondary bile acids in the stool. These results suggest that inulin alters intestinal bacterial balance and intestinal bacterial metabolism, and/or increases and/or decreases host bile acid secretion, thereby suppressing SARS-CoV-2 infection. do. Therefore, it was suggested that inulin intake can be easily incorporated into a daily routine and is a possible method to suppress the infection of the new coronavirus.
　以上、本実施形態について説明したが、上記実施形態は本発明の理解を容易にするためのものであり、本発明を限定して解釈するためのものではない。本発明は、その趣旨を逸脱することなく、変更、改良され得ると共に、本発明にはその等価物も含まれる。 Although the present embodiment has been described above, the above embodiment is for facilitating the understanding of the present invention, and is not intended to be interpreted as limiting the present invention. The present invention may be modified and improved without departing from the spirit thereof, and the present invention also includes equivalents thereof.

Claims (15)

  1. 　イヌリンを含有し、ＳＡＲＳ－ＣｏＶ－２の感染を抑制する、組成物。 A composition containing inulin and suppressing SARS-CoV-2 infection.
  2. 　前記イヌリンは、数平均分子量（Ｍｎ）が５００以上４０００以下である、請求項１に記載の組成物。 The composition according to claim 1, wherein the inulin has a number average molecular weight (Mn) of 500 or more and 4000 or less.
  3. 　前記イヌリンは、平均重合度（ＤＰ）が３以上３０以下である、請求項１又は２に記載の組成物。 The composition according to claim 1 or 2, wherein the inulin has an average degree of polymerization (DP) of 3 or more and 30 or less.
  4. 　前記イヌリンは、平均鎖長が８以上１３以下である、請求項１ないし３のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 3, wherein the inulin has an average chain length of 8 or more and 13 or less.
  5. 　前記イヌリンは、酵素法により製造されていない、請求項１ないし４のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 4, wherein the inulin is not produced by an enzymatic method.
  6. 　前記イヌリンは、チコリの根由来である、請求項１ないし５のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 5, wherein the inulin is derived from chicory root.
  7. 　胆汁酸の分泌を増加させる、請求項１ないし６のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 6, which increases the secretion of bile acids.
  8. 　胆汁酸の分泌の増加及び／又は減少によってＳＡＲＳ－ＣｏＶ－２の感染を抑制する、請求項１ないし６のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 6, which suppresses SARS-CoV-2 infection by increasing and/or decreasing bile acid secretion.
  9. 　前記胆汁酸の分泌の増加における前記胆汁酸が、リトコール酸（ＬＣＡ）、ウルソデオキシコール酸（ＵＤＣＡ）、デオキシコール酸（ＤＣＡ）、コール酸（ＣＡ）、グリコデオキシコール酸（ＧＤＣＡ）、タウロリトコール酸（ＴＬＣＡ）、タウロウルソデオキシコール酸（ＴＵＤＣＡ）、タウロデオキシコール酸（ＴＤＣＡ）及びタウロコール酸（ＴＣＡ）からなる群から選択される少なくとも一つであり、
    　前記胆汁酸の分泌の減少における前記胆汁酸が、グリコウルソデオキシコール酸（ＧＵＤＣＡ）、グリココール酸（ＧＣＡ）及びタウロケノデオキシコール酸（ＴＣＤＣＡ）からなる群から選択される少なくとも一つである、請求項８に記載の組成物。     The bile acids in the increase in bile acid secretion include lithocholic acid (LCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), cholic acid (CA), glycodeoxycholic acid (GDCA), taurolithochol at least one selected from the group consisting of acid (TLCA), tauroursodeoxycholic acid (TUDCA), taurodeoxycholic acid (TDCA), and taurocholic acid (TCA),
    12. The bile acid in the reduction of bile acid secretion is at least one selected from the group consisting of glycoursodeoxycholic acid (GUDCA), glycocholic acid (GCA), and taurochenodeoxycholic acid (TCDCA). 8. The composition according to 8.
  10. 　前記胆汁酸の分泌の増加における前記胆汁酸が、コール酸（ＣＡ）、デオキシコール酸（ＤＣＡ）及びリトコール酸（ＬＣＡ）からなる群から選択される少なくとも一つである、請求項９に記載の組成物。 10. The bile acid according to claim 9, wherein the bile acid in increasing secretion of bile acid is at least one selected from the group consisting of cholic acid (CA), deoxycholic acid (DCA), and lithocholic acid (LCA). Composition.
  11. 　Ｔｒｅｐｏｎｅｍａ　２、Ｐａｒａｂａｃｔｅｒｏｉｄｅｓ、Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ及びＡ２からなる群から選択される少なくとも一つの菌の増加及び／又はＥｉｓｅｎｂｅｒｇｉｅｌｌａ、Ｒｕｍｉｎｉｃｌｏｓｔｒｉｄｉｕｍ　５、Ｃｏｐｒｏｓｔａｎｏｌｉｇｅｎｅｓ　ｇｒｏｕｐ、Ｒｕｍｉｎｉｃｌｏｓｔｒｉｄｉｕｍ　１、Ｌａｃｔｏｃｏｃｃｕｓ、Ａｎａｅｒｏｐｌａｓｍａ、Ｂｕｔｙｒｉｃｉｍｏｎａｓ、Ｔｙｚｚｅｒｅｌｌａ及びＰｙｇｍａｉｏｂａｃｔｅｒからなる群から選択される少なくとも一つの菌の減少によってＳＡＲＳ－ＣｏＶ－２の感染を抑制する、請求項１ないし１０のいずれか一項に記載の組成物。 Increase in at least one bacterium selected from the group consisting of Treponema 2, Parabacteroides, Bifidobacterium and A2 and/or Eisenbergiella, Ruminiclostridium 5, Coprostanoligenes roup, Ruminiclostridium 1, Lactococcus, Anaeroplasma, Butyricimonas, Tyzzerella and Pygmaiobacter. The composition according to any one of claims 1 to 10, which inhibits SARS-CoV-2 infection by reducing at least one bacterium.
  12. 　請求項１ないし１１のいずれか一項に記載の組成物を含有し、ＳＡＲＳ－ＣｏＶ－２の感染を抑制する、飲食品。 A food or drink containing the composition according to any one of claims 1 to 11, which suppresses SARS-CoV-2 infection.
  13. 　請求項１ないし１１のいずれか一項に記載の組成物を含有し、ＳＡＲＳ－ＣｏＶ－２の感染を抑制する、医薬品。 A pharmaceutical product containing the composition according to any one of claims 1 to 11, which suppresses SARS-CoV-2 infection.
  14. 　胆汁酸の分泌増加のための、イヌリンの使用。 Use of inulin to increase secretion of bile acids.
  15. 　ＳＡＲＳ－ＣｏＶ－２の感染抑制のための、イヌリンの使用。

          Use of inulin to inhibit SARS-CoV-2 infection.
PCT/JP2023/012863 2022-03-30 2023-03-29 Composition, food and beverage, pharmaceutical agent, and use of inulin WO2023190710A1 (en)

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Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
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ANONYMOUS: "Enhancing immunity by promoting fermentation in the body. Bowel activities coming under spotlight. Specialized cafes are now popular, effective for prevention of novel corona and influenza virus infection", SANKEI NEWSPAPER. TOKYO MORNING EDITION, 16 October 2020 (2020-10-16), XP009550237 *
MR. FUKUDA: "Inulin, important component for fermentation in the body and improved immunity: lecture by Mr. Fukuda (Metagen) "Immune strength in the new normal era, brought by in-vitro (intestinal) fermentation", "In-vitro testing using yogurt" column)", THE JAPAN FOOD JOURNAL, NISSYOKU, JP, JP, pages 1 - 6, XP009549310, Retrieved from the Internet <URL:https://news.nissyoku.co.jp/special/686887> *
THOMAS ROBERT, ALDOUS JEFFREY, FORSYTH RACHEL, CHATER ANGEL, WILLIAMS MADELEINE, : "The Influence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the Duration and Severity of Symptoms among Individuals with Covid-19", INFECTIOUS DISEASES DIAGNOSIS & TREATMENT, vol. 5, no. 1, 16 November 2021 (2021-11-16), XP093097372, ISSN: 2577-1515, DOI: 10.29011/2577-1515.100182 *
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