WO2022045138A1 - Composition for changing occupancy in intestinal flora of specific genera of bacteria - Google Patents

Composition for changing occupancy in intestinal flora of specific genera of bacteria Download PDF

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Publication number
WO2022045138A1
WO2022045138A1 PCT/JP2021/030999 JP2021030999W WO2022045138A1 WO 2022045138 A1 WO2022045138 A1 WO 2022045138A1 JP 2021030999 W JP2021030999 W JP 2021030999W WO 2022045138 A1 WO2022045138 A1 WO 2022045138A1
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Prior art keywords
extract
daikenchuto
composition
intestinal flora
occupancy rate
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PCT/JP2021/030999
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French (fr)
Japanese (ja)
Inventor
克典 佐々木
明弘 山森
建吾 佐々木
大介 佐々木
昭彦 近藤
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住友化学株式会社
国立大学法人神戸大学
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Publication of WO2022045138A1 publication Critical patent/WO2022045138A1/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
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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)
    • 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)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • 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)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/758—Zanthoxylum, e.g. pricklyash
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9068—Zingiber, e.g. garden ginger

Definitions

  • the present invention relates to a composition for increasing the occupancy rate of Bifidobacterium and the occupancy rate of Fusobacterium in the intestinal flora and decreasing the occupancy rate of Fusobacterium.
  • the intestinal flora refers to a group of bacteria (intestinal bacteria) existing in the intestine, and is also called an intestinal flora, microbiota, or microbiome.
  • various diseases such as diabetes, atopic eczema, and dementia, and the relationship between health conditions such as obesity and the intestinal flora have been reported, and are represented by lactic acid bacteria and bifidobacteria. It has been widely pointed out that it is important to improve the intestinal flora by foods such as probiotics and prebiotics typified by dietary fiber (Non-Patent Document 1).
  • Daikenchuto is a typical Chinese medicine prescription described in the Chinese Song dynasty medical book “Kinpou”, and has an intestinal motility-enhancing effect, an intestinal hyperkinetic inhibitory effect, an intestinal obstruction (ireus) -suppressing effect, and an intestinal tract. It is known to have an effect of increasing blood flow and an anti-inflammatory effect.
  • the knowledge about the effect of Daikenchuto on the human intestinal flora is extremely limited.
  • the inventors have obtained the finding that Daikenchuto extract can significantly increase the occupancy rate (%) of Gut microbiota in the intestinal flora (Patent Document 1). It is an object of the present invention to further investigate the effect of daikenchuto on a specific bacterial genus in the intestinal flora and to provide a composition having an advantageous effect on the intestinal flora.
  • Daikenchuto extract which is a Chinese herbal drug substance, occupies the occupancy rate of Bifidobacterium spp. In the intestinal flora and the genus Coprococcus. It was found that the occupancy rate of Fusobacterium can be increased and the occupancy rate of Fusobacterium can be decreased.
  • the present invention has been completed by further studies based on these findings, and has increased the occupancy rate of Bifidobacterium spp. And Coprococcus spp. In the intestinal flora, and has been completed. It provides a composition for reducing the occupancy rate of Fusobacterium.
  • the present invention is as follows.
  • composition [1] To increase the occupancy of Bifidobacterium and Coprococcus in the intestinal flora, including an effective amount of Daikenchuto extract, and to decrease the occupancy of Fusobacterium.
  • Composition [2] The composition according to [1], wherein the Daikenchuto extract is an extract of a raw material crude drug consisting of (1) Japanese pepper and / or Japanese pepper, (2) ginseng, and (3) dried ginger. [3] The composition according to [1] or [2], wherein the Daikenchuto extract is an extract of a crude drug as a raw material, which is an extract of water, ethanol, or a mixed solvent of water and ethanol.
  • the occupancy rate of Bifidobacterium and Coprococcus in the intestinal flora can be increased and the occupancy rate of Fusobacterium can be decreased. As a result, it improves the intestinal flora and has the effect of promoting health.
  • composition of the present invention a disease or a disease that can be treated, prevented or ameliorated by increasing the occupancy rate of Bifidobacterium spp., Increasing the occupancy rate of Coprococcus spp., And decreasing the occupancy rate of Fusobacterium spp. It can contribute to the prevention, treatment or amelioration of symptoms.
  • the composition of the present invention increases the occupancy rate of Bifidobacterium spp. And Coprococcus spp. In the intestinal flora, and contains Fusobacterium spp., Containing an effective amount of Daikenchuto extract. It is a composition for reducing the occupancy rate of.
  • Bifidobacterium is a general term for microorganisms belonging to the genus Bifidobacterium of the family Bifidobacterium, and Bifidobacterium inhabiting the human intestinal tract is Bifidobacterium.
  • Bifidobacterium bifidom, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Bifidobacterium longum, Bifidobacterium longum, Bifidobacterium longum -Adolecentis (Bifidobacterium adolescentis) can be mentioned.
  • Bifidobacterium is known as a useful bacterium that decomposes sugar to produce lactic acid and acetic acid, and has an intestinal regulating effect, improvement of allergic symptoms such as pollinosis, anti-inflammatory effect, immunostimulatory effect, etc.
  • Various health benefits are known (eg, ScienceDirect overview, https://www.sciencedirect.com/topics/immunology-and-microbiology/bifidobacterium).
  • the genus Coccoccus is a general term for microorganisms belonging to the genus Lachnospiraceae, and a typical genus Coccus is Cporococcus eutactus.
  • the genus Coprococcus is a useful bacterium known as a butyric acid-producing bacterium, and is known to be involved in the suppression of colorectal cancer as a health effect. In addition, the production of butyric acid improves the intestinal environment (bad bacteria). (Suppression), immunostimulatory action, antiallergic, anti-inflammatory, and effects on diabetes are expected.
  • Fusobacterium genus is a general term for microorganisms belonging to the genus Fusobacterium of the family Fusobacterium, and a typical Fusobacterium genus is Fusobacterium nucleatum. Fusobacterium is also known as an oral bacterium, and is known to be associated with various diseases such as periodontal disease, Lemierre's syndrome, and skin ulcer, and also pointed out to be associated with ulcerative colitis and colorectal cancer. (For example, ScienceDirect overview, https://www.sciencedirect.com/topics/medicine-and-dentistry/fusobacterium).
  • Daikenchuto is described in the Chinese Song dynasty medical book “Kinpou”, and has an intestinal motility-enhancing effect, an intestinal hyperkinetic inhibitory effect, an intestinal obstruction (ireus) -suppressing effect, an intestinal blood flow increasing effect, an anti-inflammatory effect, etc.
  • Non-Patent Document 1 A typical Daikenchuto is a powdered extract of a mixed crude drug consisting of 2.0 g of Japanese pepper or Japanese pepper, 3.0 g of carrot, and 5.0 g of dried ginger. Examples thereof include powdered ginger containing about 8 times the amount of the extract.
  • Daikenchuto is a mixture of crude drugs consisting of (1) Japanese pepper or Japanese pepper, (2) carrots, and (3) Kankyo.
  • the extract of the mixture of (4) may further contain (4) Japanese pepper.
  • Those that do not contain glue candy are sometimes referred to as Koui Daikenchuto.
  • Sansho Zanthoxyli Piperiti Pericarpium
  • Sansho Zanthoxylum piperitum De Candle
  • the seeds separated from the peel are removed as much as possible. It can be prepared by collecting the fruit before ripening and drying it by removing the stalk and seeds as much as possible. It is added to the medicine to treat abdominal pain and bloating caused by cold. The main production areas are Japan and China.
  • examples of the original plant include Asakurazansho (Z. piperitum DC. F. inerme Makino) and grape sansho as variants of the original plant, and mature peels derived from these plants are also described in the present specification. Included in Sansho.
  • Zanthoxylum (Zanthoxyli Pericarpium) is a Rutaceae plant, Zanthoxylum bungeanum Maxim. Or Zanthoxylum schiniform Sieb. Et Zucc. It is the mature pericarp of the pericarp, and the seeds separated from the pericarp are removed as much as possible. It can be prepared by collecting the fruit before ripening and drying it by removing the stalk and seeds as much as possible. It is added to the medicine to treat abdominal pain and bloating caused by cold. The main production area is Sichuan province in China. In addition, as the original plant, Zanthoxylum armatum DC. Var. Subtrifoliatum Kitamura and the like are also mentioned, and mature pericarps derived from these plants are also included in the Chinese pepper in the present specification.
  • Ginseng (Ginseng Radix) is also called Korean ginseng, Korean ginseng, ginseng, white ginseng, Unshu ginseng, ginseng, and ginseng, which is an Araliaceae plant.
  • Ginseng CA Meyer Panax ginseng Nees roots excluding fine roots or lightly boiled. Ginseng promotes diminished metabolic function due to gastrointestinal weakness, chest stuffiness, loss of appetite, abdominal pain, diabetes, It is compounded in a medicinal method that improves fatigue, etc.
  • the main production areas are Japan, China and South Korea. After collecting roots and washing with water, ginseng roots and fine branch roots are removed, and ginseng (base of ginseng) ) Can be prepared by cutting it to an appropriate length, drying it in the shade, drying it in the sun, or drying it by heat.
  • Zingiberis Rhizoma Processum is a rhizome of ginger (Zingiber office Roscoe), which is a plant of the family Zingiberaceae, boiled or steamed. It is used as a medicine to improve vomiting, cough, diarrhea, cold hands and feet, and pain in the abdomen, lower back, and chest.
  • the main production area is China. It can be prepared by digging the rhizomes, removing sediment and fine roots, blanching or steaming, and then drying.
  • Koi corn (Zea mays Linne), cassava (Manihot esculenta Crantz), potato (Solanlum tuberosum Linne), sweet potato (Ipomoea batari) potato (Ipomoea battaris) P.
  • the removed seeds are hydrolyzed and saccharified, and the main component is maltose. It supplements and restores physical strength and energy, stops sputum and coughing, stimulates metabolism, and moisturizes the whole body under the control of the five organs.
  • the mass of (1) Sansho and / or Hansho is 1 part by mass
  • (2) Ginseng is 0.2 to 2.0 parts by mass
  • (3) Dried ginger is 1.0 to 3 parts. It is preferably 0.0 parts by mass, more preferably (2) 0.4 to 1.4 parts by mass of ginseng, and (3) 1.4 to 2.4 parts by mass of dried ginger. It is particularly preferable that 2) ginseng is 0.6 to 1.2 parts by mass and (3) dried ginger is 1.6 to 2.2 parts by mass.
  • the mass ratio of (1) Japanese pepper and / or Japanese pepper: (2) ginseng: (3) dried ginger may be 2: 3: 5 or 1: 1: 2.
  • Daikenchuto extract means an extract of a mixed crude drug consisting of (1) Japanese pepper and / or Japanese pepper, (2) carrot, and (3) crude drug as a raw material for dried ginger, and the extract thereof. It may be obtained by blending (4) Japanese pepper with the extract.
  • the crude drug extract is preferably extracted with a pharmaceutically acceptable aqueous solvent such as water (including hot water), ethanol or a mixed solvent of water and ethanol.
  • the extract may be produced by a known extraction method, and may be a general soft extract or extract granules.
  • the Daikenchuto extract may be obtained by mixing the raw material crude drugs and then extracting with a solvent, and the extracts obtained by extracting each raw material crude drug with a solvent are mixed at a predetermined ratio. It may be obtained by the above.
  • the composition of the present invention contains an effective amount of Daikenchuto extract to increase the occupancy rate of Bifidobacterium spp. And Coprococcus spp. In the intestinal flora, and also to increase the occupancy rate of Fusobacterium. The occupancy rate of bacteria can be reduced.
  • the effective amount (intake amount) of the Daikenchuto extract can be appropriately set according to various conditions such as the weight, age, sex, and symptoms of the ingestor. For example, a soft extract of the Daikenchuto extract.
  • the extract granules may be 0.1 to 15 g / day, and if it exceeds 15 g / day, it may lead to diarrhea, and if it is less than 0.1 g / day, the effect may not be obtained.
  • the daily intake of Daikenchuto extract may be, for example, 0.1 to 6 g or 0.1 to 3 g, or 0.5 to 4 g or 0.5 to 2 g.
  • the daily intake of the above Daikenchuto extract is obtained from the raw material crude drug consisting of (1) Japanese pepper or Japanese pepper 0.5 to 6 g, (2) Ginseng 0.5 to 6 g, and (3) Dried ginger 1 to 12 g. It is an amount corresponding to the extract to be obtained. That is, as the raw material crude drug for obtaining the above-mentioned daily amount of Daikenchuto extract, for example, a raw material crude drug consisting of 0.5 to 6 g of Japanese pepper or Japanese pepper, 0.5 to 6 g of carrot, and 1 to 12 g of dried ginger.
  • It may be a crude drug consisting of 0.5 to 2 g of Japanese pepper, 0.5 to 2 g of ginger, and 1 to 4 g of dried ginger, and 1 to 1.5 g of Japanese pepper and 1 to 1.5 g of ginger.
  • And 1.5 to 2.5 g of dried ginger may be a raw material crude drug.
  • the composition of the present invention is not limited to once a day, but can be ingested (taken) in multiple divided doses. That is, the composition of the present invention may be ingested once a day, or may be ingested in a plurality of times, for example, twice, three times or four times. When taking multiple times, the total daily dose may be the daily dose.
  • the timing of ingestion of the composition of the present invention is not particularly limited, and in the case of ingestion once a day, after waking up (within about 30 minutes from waking up time), before meals (about 30 minutes to 60 minutes before meals), and between meals.
  • composition of the present invention can be expected to have a desired effect even if it is ingested once, but in order to obtain a more sustainable effect, it is 1 week or more, preferably 2 weeks or more, more preferably 3 weeks or more. Particularly preferably, it can be continuously ingested for 4 weeks or longer, 8 weeks or longer, 3 months or longer, 6 months or longer, and 1 year or longer.
  • increasing the occupancy rate of Bifidobacterium in the intestinal flora means “Bifidobacterium in the intestinal flora after ingestion of the composition of the present invention”.
  • Occupancy rate is 0.5% or more, for example, 1% or more, 1.5% or more, 2% or more, 2.5% or more, 3% or more, 3.5% or more, 4% compared to before ingestion. As mentioned above, it means that the increase is 4.5% or more, 5% or more, or 5.5% or more.
  • the occupancy rate of bifidobacteria in the intestinal flora after ingestion of the composition of the present invention is 120% or more of the occupancy rate of bifidobacteria in the intestinal flora before ingestion. , 130% or more, 150% or more, 180% or more, or 200% or more. This does not apply to subjects who do not have Bifidobacterium spp.
  • incrementing the occupancy rate of Gut microbiota in the intestinal flora means the occupancy of Gut microbiota in the gut microbiota after ingestion of the composition of the present invention.
  • the rate is 0.25% or more, for example, 0.5% or more, 0.75% or more, 1% or more, 1.25% or more, 1.5% or more or 1.75% or more compared to before ingestion. Means to increase.
  • the occupancy rate of Gut microbiota in the intestinal flora after ingestion of the composition of the present invention is 120% or more, 130% or more of the occupancy rate of Gut microbiota in the gut microbiota before ingestion. , 150% or more, 180% or more, or 200% or more. This does not apply to subjects who do not have Coccoccus spp.
  • reducing the occupancy rate of Fusobacterium in the intestinal flora means that the occupancy rate of Fusobacterium in the intestinal flora after ingestion of the composition of the present invention is defined as. 0.5% or more, for example, 1% or more, 1.5% or more, 2% or more, 2.5% or more, 3% or more, 3.5% or more or 4% or more decrease compared to before ingestion. Means.
  • the occupancy rate of Fusobacterium in the intestinal flora after ingestion of the composition of the present invention is 90% or less, 80% or less, 70% of the occupancy rate of Fusobacterium in the intestinal flora before ingestion. It may be% or less, 60% or less, or 50% or less. This does not apply to subjects who do not have Fusobacterium spp.
  • the intestinal flora means a bacterium existing in the intestine (intestinal bacterium), and all detectable bacteria, for example, Bifidobacterium spp., Clostridium spp., Fusobacterium spp. Includes Clostridium spp., Drea spp., And Osirospira spp. Detection of gut microbiota can be performed by commonly known methods or commercially available kits. As an example, using feces as a sample, DNA in feces before and after ingestion of the composition of the present invention was purified, 16S rRNA V3-V4 region was amplified, and sequence analysis was performed using the next-generation sequencer MiSeq.
  • OTU operation taxonomy unit
  • composition of the present invention can be used for therapeutic or non-therapeutic applications.
  • composition of the present invention can be applied to mammals including humans, monkeys, mice, rats, rabbits, dogs, cats, horses, cows, pigs and the like, preferably humans.
  • composition of the present invention is effective for treatment, prevention or improvement by increasing the occupancy rate of Bifidobacterium spp. In the intestinal flora, increasing the occupancy rate of Coprococcus spp., And decreasing the occupancy rate of Fusobacterium spp. It can be used for the treatment, prevention or amelioration of a disease or symptom.
  • Inflammatory bowel diseases such as ulcerative colitis, Crohn's disease
  • allergic diseases eg, food allergies, pollinosis, asthma, allergic rhinitis, drug allergies, atopic dermatitis, tick allergies
  • diarrhea and constipation etc.
  • Intestinal diseases colon cancer, diabetes, depression, periodontal disease, Remière syndrome, skin ulcers, and other diseases thought to be caused by intestinal symbiotic imbalance (Dysbiosis) (eg, hypersensitivity intestinal syndrome, small intestinal bacterial abnormalities)
  • examples thereof include proliferative disorders (SIBO), pseudomembranous colitis (Crostridium difficile enteritis), obesity, allergic diseases, mental diseases such as autism, and polysclerosis).
  • composition of the present invention may be a food composition, a pharmaceutical composition or a quasi-drug, or may be used as an additive for foods, feeds and the like.
  • the composition of the present invention may consist only of Daikenchuto extract, and may contain components other than Daikenchuto extract.
  • the blending amount of Daikenchuto extract in the composition of the present invention can be appropriately set according to the form, dosage form, symptoms and the like, and is typically 0.1 to 100% by mass, preferably 0. It can be 1 to 99.9% by mass, more preferably 0.1 to 50% by mass, and particularly preferably 0.1 to 30% by mass.
  • composition of the present invention is not particularly limited in its form, and may have a pharmaceutical form such as jelly, powder, granule, tablet, capsule, liquid, suspension, milky liquid or the like.
  • the method for ingesting (administering) the composition of the present invention is preferably oral administration.
  • administration other than oral administration is also possible.
  • the composition of the present invention may contain a base for the purpose of efficient transportation to the intestine.
  • a general gelling agent is used, and an appropriate storage stability is required. Therefore, a base other than gelatin is preferable.
  • a gelling agent for example, carrageenan, locust bean gum, xanthan gum, polyacrylic acid, carob bean gum and the like are preferable.
  • the food composition of the present invention is intended for health, health maintenance, promotion, etc., and is preferably a food composition as prebiotics, for example, health foods, functional foods, nutritional supplements, supplements, etc.
  • prebiotics for example, health foods, functional foods, nutritional supplements, supplements, etc.
  • examples include foods for specified health use, foods with nutritional function, foods with functional claims, foods for infants, foods for pregnant women, and foods for the sick.
  • additional ingredients can be added to the food composition as needed.
  • a food material having functionality can be arbitrarily blended for the purpose of exerting a complex effect.
  • various crude drugs other than Daikenchuto extract, various probiotics, prebiotics, various oligosaccharides, vitamins, minerals and other nutritional components, and other known functional food materials can be appropriately blended.
  • food raw materials used in ordinary foods can be arbitrarily blended.
  • various general ingredients starch, gelatin, carboxymethyl cellulose, Arabic gum, locust bean gum, tragant gum, karaya gum, konjac glucomannan, xanthan gum, agar, carrageenan, polyacrylic acid, carob bean gum, alginic acid, cyclodextrin and other gelling agents.
  • the base vegetable fats and oils, animal fats and oils, processed fats and oils, seasonings, sweeteners, spices, coloring agents, preservatives, antioxidants, water and the like can be arbitrarily blended.
  • the food composition includes all foods and drinks that can be ingested by animals (including humans).
  • the type of food composition is not particularly limited, and is, for example, dairy products; fermented foods (yogurt, cheese, etc.); beverages (soft beverages such as coffee, juice, tea beverages, carbonated beverages, dairy beverages, lactic acid bacteria beverages, etc.
  • Such foods can be provided as dishes at business stores, or can be provided in a general distribution form by taking a prepared food, a retort pouch food, a frozen food, a packaging form of other general food compositions, or the like.
  • the method for producing the food composition of the present invention is not particularly limited, and a known method can be appropriately followed.
  • the administration unit form thereof is not particularly limited and can be appropriately selected, and examples thereof include tablets, capsules, granules, liquids, powders, and jellies.
  • the composition of the present invention may be a pharmaceutical composition or a non-pharmaceutical product, and in this case, it may consist only of Daikenchuto extract, which is pharmaceutically acceptable in addition to Daikenchuto extract.
  • Tablets including uncoated tablets, sugar-coated tablets, film-coated tablets, effervescent tablets, chewable tablets, troches, etc.), capsules, pills, powders (powder), along with non-toxic carriers, diluents or excipients. It can be prepared in the form of fine granules, granules, liquids, suspensions, emulsions, jellies, syrups, pastes, etc. to be pharmaceutical preparations or non-pharmaceutical products.
  • Pharmaceutically acceptable non-toxic carriers include, for example, binders, additives, fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives and the like. Will be.
  • the method for administering the pharmaceutical composition and quasi-drug of the present invention is not particularly limited, and is, for example, oral administration, rectal administration, enteral administration, oral administration, intraarterial administration, intravenous administration, transdermal administration, or the like. be able to.
  • the composition of the present invention is preferably a food composition from the viewpoint of easy availability.
  • the food composition, pharmaceutical composition, or non-pharmaceutical product of the present invention increases the occupancy rate of Bifidobacterium spp. In the intestinal flora, and increases the occupancy rate of Coprococcus spp. , Decreasing the occupancy rate of Fusobacterium spp., Improving the intestinal environment, increasing the occupancy rate of butyric acid-producing bacteria in the intestinal flora, etc. may be attached.
  • the packaging form is not particularly limited as long as it can contain a certain amount, and examples thereof include bags, wrapping paper, paper containers, soft bags, cans, bottles, and capsules.
  • the present invention comprises administering an effective amount of Daikenchuto extract to a subject in need thereof, and the occupancy rate of Bifidobacterium spp. And Coprococcus spp. In the intestinal flora.
  • a method for increasing and reducing the occupancy rate of Fusobacterium spp. treats, prevents or ameliorate diseases and conditions that can be treated, prevented or ameliorated by increasing the occupancy rate of Bifidobacterium spp., Increasing the occupancy rate of Coprococcus spp., And decreasing the occupancy rate of Fusobacterium spp. It may be a method.
  • the present invention also increases the occupancy rate of Bifidobacterium and Coprococcus in the intestinal flora of an effective amount of Daikenchuto extract, and also increases the occupancy of Fusobacterium. Provided for use in the manufacture of compositions for reducing.
  • the present invention further increases the occupancy rate of Bifidobacterium spp. And Coprococcus spp. In the intestinal flora, and reduces the occupancy rate of Fusobacterium spp. Provide the use of Nakato extract.
  • Example 1 Human fecal anaerobic culture test (preparation of composition)
  • Commercially available Japanese pepper manufactured by Ryu Fukuda Co., Ltd.
  • ginseng Ginseng; manufactured by Keien Japan Co., Ltd.
  • dried ginger Zhejiang Keimatsu Pharmaceutical Co., Ltd., China
  • a soft extract of ginseng was prepared by boiling and extracting with% hydrous ethanol, filtering, concentrating, and sterilizing. 1.25 g of Daikenchuto soft extract was obtained for 1 g of Japanese pepper, 1 g of ginseng, and 2 g of dried ginger.
  • feces collected from four donors F32 (32-year-old female), F42b (42-year-old female), M39 (39-year-old male), M41 (41-year-old male)
  • F32 32-year-old female
  • F42b 42-year-old female
  • M39 39-year-old male
  • M41 41-year-old male
  • Daikenchuto extract was added to each fecal incubator at 0.5% by mass at the start of culturing.
  • fecal incubators to which Daikenchuto extract was not added were prepared and a culture test was conducted.

Abstract

The purpose of the present invention is to provide a composition having an advantageous effect on intestinal flora, based on studying the effects of daikenchuto on specific genera of bacteria in intestinal flora. A composition according to the present invention comprises an effective amount of daikenchuto extract, and is for increasing the occupancy in intestinal flora of bacteria of the genus Bifidobacterium and bacteria of the genus Coprococcus, and reducing the occupancy in intestinal flora of bacteria of the genus Fusobacterium.

Description

腸内菌叢中の特定の細菌属の占有率を変化させるための組成物Composition for changing the occupancy of a particular bacterial genus in the gut flora
　本発明は、腸内菌叢中のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム菌の占有率を減少させるための組成物に関する。 The present invention relates to a composition for increasing the occupancy rate of Bifidobacterium and the occupancy rate of Fusobacterium in the intestinal flora and decreasing the occupancy rate of Fusobacterium.
　腸内菌叢（腸内細菌叢）とは、腸内に存在する細菌（腸内細菌）の集団のことをいい、腸内フローラやミクロビオータ（ｍｉｃｒｏｂｉｏｔａ）、ミクロビオーム（ｍｉｃｒｏｂｉｏｍｅ）とも呼ばれる。近年、各種腸疾患に加えて、糖尿病、アトピー性湿疹、認知症等の様々な疾患、さらに肥満等の健康状態と腸内菌叢との関連性が報告されており、乳酸菌及びビフィズス菌に代表されるプロバイオティクス、食物繊維に代表されるプレバイオティクス等の食品によって腸内菌叢を改善する重要性が広く指摘されている（非特許文献１）。 The intestinal flora (intestinal flora) refers to a group of bacteria (intestinal bacteria) existing in the intestine, and is also called an intestinal flora, microbiota, or microbiome. In recent years, in addition to various intestinal diseases, various diseases such as diabetes, atopic eczema, and dementia, and the relationship between health conditions such as obesity and the intestinal flora have been reported, and are represented by lactic acid bacteria and bifidobacteria. It has been widely pointed out that it is important to improve the intestinal flora by foods such as probiotics and prebiotics typified by dietary fiber (Non-Patent Document 1).
　一方、大建中湯は、中国宋時代の医書「金匱要略」に記載されている代表的な漢方処方であり、腸管運動亢進作用、腸管過剰運動抑制作用、腸閉塞（イレウス）抑制作用、腸管血流増加作用、抗炎症作用などを有することが知られている。しかしながら、大建中湯がヒト腸内菌叢に及ぼす作用に関する知見は極めて限定されている。 On the other hand, Daikenchuto is a typical Chinese medicine prescription described in the Chinese Song dynasty medical book "Kinpou", and has an intestinal motility-enhancing effect, an intestinal hyperkinetic inhibitory effect, an intestinal obstruction (ireus) -suppressing effect, and an intestinal tract. It is known to have an effect of increasing blood flow and an anti-inflammatory effect. However, the knowledge about the effect of Daikenchuto on the human intestinal flora is extremely limited.
国際公開第２０２０／１７９８１０号International Publication No. 2020/179810 特許第６４８２１３５号Patent No. 6482135
　発明者らは、大建中湯エキスが、腸内菌叢中のフィーカリバクテリウム属菌の占有率（％）を有意に増加させることができるという知見を得た（特許文献１）。本発明は、腸内菌叢中の特定の細菌属に対する大建中湯の影響をさらに検討し、腸内菌叢に対する有利な効果を有する組成物を提供することを目的とする。 The inventors have obtained the finding that Daikenchuto extract can significantly increase the occupancy rate (%) of Gut microbiota in the intestinal flora (Patent Document 1). It is an object of the present invention to further investigate the effect of daikenchuto on a specific bacterial genus in the intestinal flora and to provide a composition having an advantageous effect on the intestinal flora.
　本発明者らは、上記目的を達成すべく鋭意研究を重ねた結果、漢方原薬である大建中湯エキスが、腸内菌叢中のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム菌の占有率を減少させることができるという知見を得た。 As a result of diligent research to achieve the above object, the present inventors have found that Daikenchuto extract, which is a Chinese herbal drug substance, occupies the occupancy rate of Bifidobacterium spp. In the intestinal flora and the genus Coprococcus. It was found that the occupancy rate of Fusobacterium can be increased and the occupancy rate of Fusobacterium can be decreased.
　本発明は、これら知見に基づき、更に検討を重ねて完成されたものであり、腸内菌叢中のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム菌の占有率を減少させるための組成物を提供するものである。 The present invention has been completed by further studies based on these findings, and has increased the occupancy rate of Bifidobacterium spp. And Coprococcus spp. In the intestinal flora, and has been completed. It provides a composition for reducing the occupancy rate of Fusobacterium.
　すなわち、本発明は、以下のとおりである。 That is, the present invention is as follows.
［１］
　有効量の大建中湯エキスを含む、腸内菌叢中のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム属菌の占有率を減少させるための組成物。
［２］
　大建中湯エキスが、（１）山椒及び／又は花椒、（２）人参、並びに（３）乾姜からなる原料生薬のエキスである、［１］に記載の組成物。
［３］
　大建中湯エキスが、原料生薬の、水、エタノール、或いは、水とエタノールとの混合溶媒の抽出エキスである、［１］又は［２］に記載の組成物。
［４］
　大建中湯エキスの１日摂取量が０．１～１５ｇである、［１］～［３］のいずれかに記載の組成物。
［５］
　大建中湯エキスの１日摂取量が０．１～３ｇである、［１］～［４］のいずれかに記載の組成物。
［６］
　大建中湯エキスの原料生薬において、（１）山椒及び／又は花椒の質量を１質量部とした場合、（２）人参が０．２～２．０質量部、（３）乾姜が１．０～３．０質量部である、［１］～［５］のいずれかに記載の組成物。
［７］
　大建中湯エキスの原料生薬において、（１）山椒及び／又は花椒の質量を１質量部とした場合、（２）人参が０．４～１．４質量部、（３）乾姜が１．４～２．４質量部である、［１］～［６］のいずれかに記載の組成物。
［８］
　大建中湯エキスの１日摂取量が、（１）山椒又は花椒０．５～６ｇ、（２）人参０．５～６ｇ、並びに（３）乾姜１～１２ｇからなる原料生薬から得られるエキスに相当する量である、［１］～［７］のいずれかに記載の組成物。
［９］
　食品組成物である、［１］～［８］のいずれかに記載の組成物。 [1]
To increase the occupancy of Bifidobacterium and Coprococcus in the intestinal flora, including an effective amount of Daikenchuto extract, and to decrease the occupancy of Fusobacterium. Composition.
[2]
The composition according to [1], wherein the Daikenchuto extract is an extract of a raw material crude drug consisting of (1) Japanese pepper and / or Japanese pepper, (2) ginseng, and (3) dried ginger.
[3]
The composition according to [1] or [2], wherein the Daikenchuto extract is an extract of a crude drug as a raw material, which is an extract of water, ethanol, or a mixed solvent of water and ethanol.
[4]
The composition according to any one of [1] to [3], wherein the daily intake of Daikenchuto extract is 0.1 to 15 g.
[5]
The composition according to any one of [1] to [4], wherein the daily intake of Daikenchuto extract is 0.1 to 3 g.
[6]
In the crude drug of the raw material of Daikenchuto extract, when (1) Japanese pepper and / or Chinese pepper is 1 part by mass, (2) 0.2 to 2.0 parts by mass of ginseng and (3) 1 part of dried ginger. .. The composition according to any one of [1] to [5], which is 0 to 3.0 parts by mass.
[7]
In the crude drug used as the raw material for Daikenchuto extract, when (1) Japanese pepper and / or Chinese pepper is 1 part by mass, (2) 0.4 to 1.4 parts by mass of ginseng and (3) 1 part of dried ginger. The composition according to any one of [1] to [6], which is .4 to 2.4 parts by mass.
[8]
The daily intake of Daikenchuto extract is obtained from raw herbal medicine consisting of (1) Japanese pepper or Japanese pepper 0.5-6g, (2) Ginseng 0.5-6g, and (3) Dry ginger 1-12g. The composition according to any one of [1] to [7], which is an amount corresponding to an extract.
[9]
The composition according to any one of [1] to [8], which is a food composition.
　本発明の組成物によれば、腸内菌叢における、ビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム菌の占有率を減少させることができ、それによって、腸内菌叢を改善し、健康促進との効果を奏する。 According to the composition of the present invention, the occupancy rate of Bifidobacterium and Coprococcus in the intestinal flora can be increased and the occupancy rate of Fusobacterium can be decreased. As a result, it improves the intestinal flora and has the effect of promoting health.
　また、本発明の組成物によれば、ビフィドバクテリウム属菌の占有率増加、コプロコッカス属菌の占有率増加、及び、フソバクテリウム属菌の占有率減少により治療、予防又は改善し得る疾患又は症状の予防、治療又は改善に寄与し得る。 Further, according to the composition of the present invention, a disease or a disease that can be treated, prevented or ameliorated by increasing the occupancy rate of Bifidobacterium spp., Increasing the occupancy rate of Coprococcus spp., And decreasing the occupancy rate of Fusobacterium spp. It can contribute to the prevention, treatment or amelioration of symptoms.
　以下、本発明について詳細に説明する。 Hereinafter, the present invention will be described in detail.
　なお、本明細書において「含む（ｃｏｍｐｒｉｓｅ）」とは、「本質的にからなる（ｅｓｓｅｎｔｉａｌｌｙ　ｃｏｎｓｉｓｔ　ｏｆ）」という意味と、「のみからなる（ｃｏｎｓｉｓｔ　ｏｆ）」という意味をも包含する。 In addition, in this specification, "comprise" also includes the meaning of "essentially consist of" and the meaning of "consist of only".
　本発明の組成物は、有効量の大建中湯エキスを含む、腸内菌叢中のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム属菌の占有率を減少させるための組成物である。 The composition of the present invention increases the occupancy rate of Bifidobacterium spp. And Coprococcus spp. In the intestinal flora, and contains Fusobacterium spp., Containing an effective amount of Daikenchuto extract. It is a composition for reducing the occupancy rate of.
　ビフィドバクテリウム属（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ）菌とは、ビフィドバクテリウム科（Ｂｉｆｉｄｏｂａｃｔｅｒｉａｃｅａｅ）ビフィドバクテリウム属に属する微生物の総称であり、ヒトの腸管に棲息するビフィドバクテリウム属菌としては、ビフィドバクテリウム・ビフィダム（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ　ｂｉｆｉｄｕｍ）、ビフィドバクテリウム・ブレーベ（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ　ｂｒｅｖｅ）、ビフィドバクテリウム・インファンティス（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ　ｉｎｆａｎｔｉｓ）、ビフィドバクテリウム・ロンガム（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ　ｌｏｎｇｕｍ）、及び、ビフィドバクテリウム・アドレセンティス（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ　ａｄｏｌｅｓｃｅｎｔｉｓ）が挙げられる。ビフィドバクテリウム属菌は糖を分解し、乳酸、酢酸を産生する有用菌として知られており、整腸作用や花粉症をはじめとするアレルギー症状の改善、抗炎症作用、免疫賦活作用等、種々の健康効果が知られている（例えば、ScienceDirect overview, https://www.sciencedirect.com/topics/immunology-and-microbiology/bifidobacterium）。 Bifidobacterium is a general term for microorganisms belonging to the genus Bifidobacterium of the family Bifidobacterium, and Bifidobacterium inhabiting the human intestinal tract is Bifidobacterium. Bifidobacterium bifidom, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Bifidobacterium longum, Bifidobacterium longum, Bifidobacterium longum -Adolecentis (Bifidobacterium adolescentis) can be mentioned. Bifidobacterium is known as a useful bacterium that decomposes sugar to produce lactic acid and acetic acid, and has an intestinal regulating effect, improvement of allergic symptoms such as pollinosis, anti-inflammatory effect, immunostimulatory effect, etc. Various health benefits are known (eg, ScienceDirect overview, https://www.sciencedirect.com/topics/immunology-and-microbiology/bifidobacterium).
　コプロコッカス属（Ｃｏｐｒｏｃｏｃｃｕｓ）菌とは、ラクノスピラ科（Ｌａｃｈｎｏｓｐｉｒａｃｅａｅ）コプロコッカス属に属する微生物の総称であり、代表的なコプロコッカス属菌としては、コプロコッカス・ユータクタス（Ｃｐｏｒｏｃｏｃｃｕｓ　ｅｕｔａｃｔｕｓ）が挙げられる。コプロコッカス属菌は酪酸産生菌として知られる有用菌であり、健康効果として大腸がんの抑制に関与することが知られている他、酪酸を産生することで腸内環境の改善（悪玉菌の抑制）、免疫賦活作用、抗アレルギー性、抗炎症、また糖尿病への効果等が期待される。更には、うつ病患者での枯渇が認められるなど、精神疾患との関連も報告されている（例えば、ScienceDirect overview, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/coprococcus）。 The genus Coccoccus is a general term for microorganisms belonging to the genus Lachnospiraceae, and a typical genus Coccus is Cporococcus eutactus. The genus Coprococcus is a useful bacterium known as a butyric acid-producing bacterium, and is known to be involved in the suppression of colorectal cancer as a health effect. In addition, the production of butyric acid improves the intestinal environment (bad bacteria). (Suppression), immunostimulatory action, antiallergic, anti-inflammatory, and effects on diabetes are expected. Furthermore, it has been reported that it is associated with psychiatric disorders, such as depletion in depressed patients (for example, ScienceDirect overview, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/). coprococcus).
　フソバクテリウム属（Ｆｕｓｏｂａｃｔｅｒｉｕｍ）菌とは、フソバクテリウム科（Ｆｕｓｏｂａｃｔｅｒｉａｃｅａｅ）フソバクテリウム属に属する微生物の総称であり、代表的なフソバクテリウム属菌としては、フソバクテリウム・ヌクレアタム（Ｆｕｓｏｂａｃｔｅｒｉｕｍ　ｎｕｃｌｅａｔｕｍ）が挙げられる。フソバクテリウム属菌は口腔細菌としても知られており、歯周病やレミエール症候群、皮膚潰瘍等の種々の疾患との関連が知られている他、潰瘍性大腸炎や大腸がんとの関連も指摘されている（例えば、ScienceDirect overview, https://www.sciencedirect.com/topics/medicine-and-dentistry/fusobacterium）。 Fusobacterium genus is a general term for microorganisms belonging to the genus Fusobacterium of the family Fusobacterium, and a typical Fusobacterium genus is Fusobacterium nucleatum. Fusobacterium is also known as an oral bacterium, and is known to be associated with various diseases such as periodontal disease, Lemierre's syndrome, and skin ulcer, and also pointed out to be associated with ulcerative colitis and colorectal cancer. (For example, ScienceDirect overview, https://www.sciencedirect.com/topics/medicine-and-dentistry/fusobacterium).
　大建中湯は、中国宋時代の医書「金匱要略」に記載されており、腸管運動亢進作用、腸管過剰運動抑制作用、腸閉塞（イレウス）抑制作用、腸管血流増加作用、抗炎症作用などを有するとされている（非特許文献１）。典型的な大建中湯としては、山椒若しくは花椒２．０ｇ、人参３．０ｇ、乾姜５．０ｇからなる混合生薬の抽出エキスを粉末化したもの（無コウイ大建中湯）に、抽出エキスの８倍量程度の粉末膠飴を配合したものが挙げられる。 Daikenchuto is described in the Chinese Song dynasty medical book "Kinpou", and has an intestinal motility-enhancing effect, an intestinal hyperkinetic inhibitory effect, an intestinal obstruction (ireus) -suppressing effect, an intestinal blood flow increasing effect, an anti-inflammatory effect, etc. (Non-Patent Document 1). A typical Daikenchuto is a powdered extract of a mixed crude drug consisting of 2.0 g of Japanese pepper or Japanese pepper, 3.0 g of carrot, and 5.0 g of dried ginger. Examples thereof include powdered ginger containing about 8 times the amount of the extract.
　本明細書において大建中湯は、（１）山椒（サンショウ）若しくは花椒（カショウ）、（２）人参（ニンジン）、並びに（３）乾姜（カンキョウ）からなる原料生薬の混合物又は原料生薬の混合物のエキスをいい、（４）膠飴（コウイ）をさらに含んでもよい。膠飴を含まないものを無コウイ大建中湯と称されることがある。 In the present specification, Daikenchuto is a mixture of crude drugs consisting of (1) Japanese pepper or Japanese pepper, (2) carrots, and (3) Kankyo. The extract of the mixture of (4) may further contain (4) Japanese pepper. Those that do not contain glue candy are sometimes referred to as Koui Daikenchuto.
　山椒（サンショウ；Ｚａｎｔｈｏｘｙｌｉ　Ｐｉｐｅｒｉｔｉ　Ｐｅｒｉｃａｒｐｉｕｍ）は、ミカン科（Ｒｕｔａｃｅａｅ）植物であるサンショウ（Ｚａｎｔｈｏｘｙｌｕｍ　ｐｉｐｅｒｉｔｕｍ　Ｄｅ　Ｃａｎｄｏｌｌｅ）の成熟果皮であって、果皮から分離した種子をできるだけ除いたものである。果実の成熟前に採取し、果柄、種子をできるだけ除き乾燥させることによって調製できる。冷えによる腹痛・膨満感を治療する薬方に配合される。主な産地は、日本及び中国である。また、原植物として、基原植物の変種としての、アサクラザンショウ（Ｚ．　ｐｉｐｅｒｉｔｕｍ　ＤＣ．　ｆ．　ｉｎｅｒｍｅ　Ｍａｋｉｎｏ）、ブドウサンショウなども挙げられ、これらの植物由来の成熟した果皮も本願明細書における山椒に含まれる。 Sansho (Zanthoxyli Piperiti Pericarpium) is the mature peel of Sansho (Zanthoxylum piperitum De Candle), which is a Rutaceae plant, and the seeds separated from the peel are removed as much as possible. It can be prepared by collecting the fruit before ripening and drying it by removing the stalk and seeds as much as possible. It is added to the medicine to treat abdominal pain and bloating caused by cold. The main production areas are Japan and China. In addition, examples of the original plant include Asakurazansho (Z. piperitum DC. F. inerme Makino) and grape sansho as variants of the original plant, and mature peels derived from these plants are also described in the present specification. Included in Sansho.
　花椒（カショウ；Ｚａｎｔｈｏｘｙｌｉ　Ｐｅｒｉｃａｒｐｉｕｍ）は、ミカン科（Ｒｕｔａｃｅａｅ）植物であるカショウ（Ｚａｎｔｈｏｘｙｌｕｍ　ｂｕｎｇｅａｎｕｍ　Ｍａｘｉｍ．）又はＺａｎｔｈｏｘｙｌｕｍ　ｓｃｈｉｎｉｆｏｌｉｕｍ　Ｓｉｅｂ．　ｅｔ　Ｚｕｃｃ．の成熟果皮であって、果皮から分離した種子をできるだけ除いたものである。果実の成熟前に採取し、果柄、種子をできるだけ除き乾燥させることによって調製できる。冷えによる腹痛・膨満感を治療する薬方に配合される。主な産地は中国の四川省である。また、原植物としては、Ｚａｎｔｈｏｘｙｌｕｍ　ａｒｍａｔｕｍ　ＤＣ．　ｖａｒ．　ｓｕｂｔｒｉｆｏｌｉａｔｕｍ　Ｋｉｔａｍｕｒａなども挙げられ、これらの植物由来の成熟した果皮も本願明細書における花椒に含まれる。 Zanthoxylum (Zanthoxyli Pericarpium) is a Rutaceae plant, Zanthoxylum bungeanum Maxim. Or Zanthoxylum schiniform Sieb. Et Zucc. It is the mature pericarp of the pericarp, and the seeds separated from the pericarp are removed as much as possible. It can be prepared by collecting the fruit before ripening and drying it by removing the stalk and seeds as much as possible. It is added to the medicine to treat abdominal pain and bloating caused by cold. The main production area is Sichuan Province in China. In addition, as the original plant, Zanthoxylum armatum DC. Var. Subtrifoliatum Kitamura and the like are also mentioned, and mature pericarps derived from these plants are also included in the Chinese pepper in the present specification.
　人参（ニンジン；Ｇｉｎｓｅｎｇ　Ｒａｄｉｘ）は、朝鮮人参、高麗人参、御種人参、白参、雲州人参、生干（しょうぼし）人参などとも呼ばれ、ウコギ科（Ａｒａｌｉａｃｅａｅ）植物であるオタネニンジン（Ｐａｎａｘ　ｇｉｎｓｅｎｇ　Ｃ．Ａ．　Ｍｅｙｅｒ（Ｐａｎａｘ　ｓｃｈｉｎｓｅｎｇ　Ｎｅｅｓ）の細根を除いた根又はこれを軽く湯通ししたものである。胃腸の衰弱による新陳代謝機能の減退を振興し、胸部のつかえ、食欲不振、腹痛、糖尿、疲労などを改善する薬方に配合する。主な産地は日本、中国及び韓国である。根を採取し、水洗後ひげ根及び細い分枝根を除去し、芦頭（ろず）（地上茎基部）を適当な長さに切除して陰干し、天日干し又は火力乾燥することによって調製できる。 Ginseng (Ginseng Radix) is also called Korean ginseng, Korean ginseng, ginseng, white ginseng, Unshu ginseng, ginseng, and ginseng, which is an Araliaceae plant. Ginseng CA Meyer (Panax ginseng Nees) roots excluding fine roots or lightly boiled. Ginseng promotes diminished metabolic function due to gastrointestinal weakness, chest stuffiness, loss of appetite, abdominal pain, diabetes, It is compounded in a medicinal method that improves fatigue, etc. The main production areas are Japan, China and South Korea. After collecting roots and washing with water, ginseng roots and fine branch roots are removed, and ginseng (base of ginseng) ) Can be prepared by cutting it to an appropriate length, drying it in the shade, drying it in the sun, or drying it by heat.
　乾姜（カンキョウ；Ｚｉｎｇｉｂｅｒｉｓ　Ｒｈｉｚｏｍａ　Ｐｒｏｃｅｓｓｕｍ）は、ショウガ科（Ｚｉｎｇｉｂｅｒａｃｅａｅ）植物であるショウガ（Ｚｉｎｇｉｂｅｒ　ｏｆｆｉｃｉｎａｌｅ　Ｒｏｓｃｏｅ）の根茎を湯通し又は蒸したものである。嘔吐、咳、下痢、手足の冷え、腹部・腰部・胸部の疼痛を改善する薬方に配合される。主な産地は中国である。根茎を掘り取り、土砂と細根を取り除いて、湯通しまたは蒸した後、乾燥することによって調製できる。 Zingiberis Rhizoma Processum is a rhizome of ginger (Zingiber office Roscoe), which is a plant of the family Zingiberaceae, boiled or steamed. It is used as a medicine to improve vomiting, cough, diarrhea, cold hands and feet, and pain in the abdomen, lower back, and chest. The main production area is China. It can be prepared by digging the rhizomes, removing sediment and fine roots, blanching or steaming, and then drying.
　膠飴（コウイ；Ｋｏｉ）は、トウモロコシ（Ｚｅａ　ｍａｙｓ　Ｌｉｎｎｅ）、キャッサバ（Ｍａｎｉｈｏｔ　ｅｓｃｕｌｅｎｔａ　Ｃｒａｎｔｚ）、ジャガイモ（Ｓｏｌａｎｌｕｍ　ｔｕｂｅｒｏｓｕｍ　Ｌｉｎｎｅ）、サツマイモ（Ｉｐｏｍｏｅａ　ｂａｔａｔａｓ　Ｐｏｉｒｅｔ）又はイネ（Ｏｒｉｙｚａ　ｓａｔｉｖａ　Ｌｉｎｎｅ）のデンプン又はイネの種皮を除いた種子を加水分解し、糖化したものであり、その主成分はマルトースである。体力、気力を補い回復させ、痰、咳嗽を止め、新陳代謝を盛んにし五臓支配下の全身に潤いをつける。 Koi is corn (Zea mays Linne), cassava (Manihot esculenta Crantz), potato (Solanlum tuberosum Linne), sweet potato (Ipomoea batari) potato (Ipomoea battaris) P. The removed seeds are hydrolyzed and saccharified, and the main component is maltose. It supplements and restores physical strength and energy, stops sputum and coughing, stimulates metabolism, and moisturizes the whole body under the control of the five organs.
　原料生薬において、（１）山椒及び／又は花椒の質量を１質量部とした場合、（２）人参が０．２～２．０質量部であり、（３）乾姜が１．０～３．０質量部であることが好ましく、（２）人参が０．４～１．４質量部であり、（３）乾姜が１．４～２．４質量部であることがより好ましく、（２）人参が０．６～１．２質量部であり、（３）乾姜が１．６～２．２質量部であることが特に好ましい。例えば、（１）山椒及び／又は花椒：（２）人参：（３）乾姜の質量比が２：３：５又は１：１：２であってよい。 In the raw material raw medicine, when the mass of (1) Sansho and / or Hansho is 1 part by mass, (2) Ginseng is 0.2 to 2.0 parts by mass, and (3) Dried ginger is 1.0 to 3 parts. It is preferably 0.0 parts by mass, more preferably (2) 0.4 to 1.4 parts by mass of ginseng, and (3) 1.4 to 2.4 parts by mass of dried ginger. It is particularly preferable that 2) ginseng is 0.6 to 1.2 parts by mass and (3) dried ginger is 1.6 to 2.2 parts by mass. For example, the mass ratio of (1) Japanese pepper and / or Japanese pepper: (2) ginseng: (3) dried ginger may be 2: 3: 5 or 1: 1: 2.
　本明細書において、大建中湯エキスは、上記（１）山椒及び／又は花椒、（２）人参、並びに（３）乾姜原料生薬からなる混合生薬の抽出エキスを意味し、また、当該抽出エキスに（４）膠飴を配合して得られるものであってよい。本願明細書において、生薬のエキスとは、製薬上許容される水性溶媒、例えば、水（熱水を含む）、エタノール又は水とエタノールとの混合溶媒によって抽出されたものであることが好ましい。エキスは、公知の抽出方法によって作製されるものであってよく、一般的な軟エキス又はエキス顆粒であってよい。大建中湯エキスは、原料生薬を混合してから溶媒で抽出して得られたものであってもよく、それぞれの原料生薬を溶媒で抽出して得られたエキスを所定の比率で混合して得られたものであってもよい。 In the present specification, Daikenchuto extract means an extract of a mixed crude drug consisting of (1) Japanese pepper and / or Japanese pepper, (2) carrot, and (3) crude drug as a raw material for dried ginger, and the extract thereof. It may be obtained by blending (4) Japanese pepper with the extract. In the present specification, the crude drug extract is preferably extracted with a pharmaceutically acceptable aqueous solvent such as water (including hot water), ethanol or a mixed solvent of water and ethanol. The extract may be produced by a known extraction method, and may be a general soft extract or extract granules. The Daikenchuto extract may be obtained by mixing the raw material crude drugs and then extracting with a solvent, and the extracts obtained by extracting each raw material crude drug with a solvent are mixed at a predetermined ratio. It may be obtained by the above.
　本発明の組成物は有効量の大建中湯エキスを含むことで、腸内菌叢中のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム属菌の占有率を減少させることができる。前記大建中湯エキスの有効量（摂取量）は、摂取者の体重、年齢、性別、症状などの種々の条件に応じて適宜設定することができ、例えば、大建中湯エキスの軟エキス又はエキス顆粒として、０．１～１５ｇ／日であればよく、１５ｇ／日を超えると、下痢につながる虞があり、０．１ｇ／日よりも少ないと効果が得られない虞がある。大建中湯エキスの１日摂取量が、例えば、０．１～６ｇ又は０．１～３ｇであってもよく、或いは、０．５～４ｇ又は０．５～２ｇであってもよい。 The composition of the present invention contains an effective amount of Daikenchuto extract to increase the occupancy rate of Bifidobacterium spp. And Coprococcus spp. In the intestinal flora, and also to increase the occupancy rate of Fusobacterium. The occupancy rate of bacteria can be reduced. The effective amount (intake amount) of the Daikenchuto extract can be appropriately set according to various conditions such as the weight, age, sex, and symptoms of the ingestor. For example, a soft extract of the Daikenchuto extract. Alternatively, the extract granules may be 0.1 to 15 g / day, and if it exceeds 15 g / day, it may lead to diarrhea, and if it is less than 0.1 g / day, the effect may not be obtained. The daily intake of Daikenchuto extract may be, for example, 0.1 to 6 g or 0.1 to 3 g, or 0.5 to 4 g or 0.5 to 2 g.
　上記大建中湯エキスの１日摂取量が、（１）山椒又は花椒０．５～６ｇ、（２）人参０．５～６ｇ、並びに（３）乾姜１～１２ｇからなる原料生薬から得られるエキスに相当する量である。すなわち、上記の１日量の大建中湯エキスを得るための原料生薬として、例えば、山椒又は花椒０．５～６ｇ、人参０．５～６ｇ、及び乾姜１～１２ｇからなる原料生薬を挙げることができ、また、花椒０．５～２ｇ、人参０．５～２ｇ、及び乾姜１～４ｇからなる原料生薬であってもよく、花椒１～１．５ｇ、人参１～１．５ｇ、及び乾姜１．５～２．５ｇからなる原料生薬であってもよい。 The daily intake of the above Daikenchuto extract is obtained from the raw material crude drug consisting of (1) Japanese pepper or Japanese pepper 0.5 to 6 g, (2) Ginseng 0.5 to 6 g, and (3) Dried ginger 1 to 12 g. It is an amount corresponding to the extract to be obtained. That is, as the raw material crude drug for obtaining the above-mentioned daily amount of Daikenchuto extract, for example, a raw material crude drug consisting of 0.5 to 6 g of Japanese pepper or Japanese pepper, 0.5 to 6 g of carrot, and 1 to 12 g of dried ginger. It may be a crude drug consisting of 0.5 to 2 g of Japanese pepper, 0.5 to 2 g of ginger, and 1 to 4 g of dried ginger, and 1 to 1.5 g of Japanese pepper and 1 to 1.5 g of ginger. , And 1.5 to 2.5 g of dried ginger may be a raw material crude drug.
　本発明の組成物の摂取は、１日１回に限らず、複数回に分割して摂取（服用）することもできる。すなわち、本発明の組成物の摂取は１日１回であってもよく、複数回、例えば２回、３回又は４回に分けて摂取してもよい。複数回摂取する場合は、１日の合計量が１日量となるように摂取すればよい。本発明の組成物の摂取タイミングは特に限定されず、１日１回の摂取の場合、起床後（起床時間から約３０分以内）、食前（食事の約３０分前から６０分前）、食間（食事の約２時間後）、食後（食後約３０分以内）、就寝前（就寝時間の約３０分前）等任意の時間で摂取してもよく、大建中湯は腸管運動を促進することを考慮すれば、食前又は食間が好ましく、また、摂取後に腹部にゴロゴロ感をもたらし、おならが出る可能性があるため、就寝前の摂取であってもよい。１日複数回の摂取の場合、起床後、食前、食間、食後、就寝前のうちの２つ、３つ又は４つ以上のタイミングで摂取してもよい。また、食事と同時に摂取してもよい。 The composition of the present invention is not limited to once a day, but can be ingested (taken) in multiple divided doses. That is, the composition of the present invention may be ingested once a day, or may be ingested in a plurality of times, for example, twice, three times or four times. When taking multiple times, the total daily dose may be the daily dose. The timing of ingestion of the composition of the present invention is not particularly limited, and in the case of ingestion once a day, after waking up (within about 30 minutes from waking up time), before meals (about 30 minutes to 60 minutes before meals), and between meals. It may be taken at any time (about 2 hours after meal), after meal (within about 30 minutes after meal), before bedtime (about 30 minutes before bedtime), and Daikenchuto promotes intestinal motility. Considering this, it is preferable to take it before or between meals, and it may be taken before bedtime because it causes a lumpy feeling in the abdomen after ingestion and may cause a sickness. In the case of multiple ingestions per day, it may be taken at two, three or four or more timings after waking up, before meals, between meals, after meals, and before going to bed. It may also be taken at the same time as meals.
　本発明の組成物は１回の摂取であっても所望の効果が期待できるが、より持続的な効果を得るためには、１週間以上、好ましくは２週間以上、より好ましくは３週間以上、特に好ましくは４週間以上、８週間以上、３ヶ月以上、６か月以上、１年以上継続して摂取することができる。 The composition of the present invention can be expected to have a desired effect even if it is ingested once, but in order to obtain a more sustainable effect, it is 1 week or more, preferably 2 weeks or more, more preferably 3 weeks or more. Particularly preferably, it can be continuously ingested for 4 weeks or longer, 8 weeks or longer, 3 months or longer, 6 months or longer, and 1 year or longer.
　本明細書において、「腸内菌叢中のビフィドバクテリウム属菌の占有率を増加させる」こととは、本発明の組成物の摂取後の腸内菌叢中のビフィドバクテリウム属菌の占有率が、摂取前と比べて、０．５％以上、例えば１％以上、１．５％以上、２％以上、２．５％以上、３％以上、３．５％以上、４％以上、４．５％以上、５％以上又は５．５％以上増加することを意味する。また、本発明の組成物の摂取後の腸内菌叢中のビフィドバクテリウム属菌の占有率は、摂取前の腸内菌叢中のビフィドバクテリウム属菌の占有率の１２０％以上、１３０％以上、１５０％以上、１８０％以上、又は２００％以上であってもよい。なお、ビフィドバクテリウム属菌を有しない対象においては、この限りでない。 In the present specification, "increasing the occupancy rate of Bifidobacterium in the intestinal flora" means "Bifidobacterium in the intestinal flora after ingestion of the composition of the present invention". Occupancy rate is 0.5% or more, for example, 1% or more, 1.5% or more, 2% or more, 2.5% or more, 3% or more, 3.5% or more, 4% compared to before ingestion. As mentioned above, it means that the increase is 4.5% or more, 5% or more, or 5.5% or more. In addition, the occupancy rate of bifidobacteria in the intestinal flora after ingestion of the composition of the present invention is 120% or more of the occupancy rate of bifidobacteria in the intestinal flora before ingestion. , 130% or more, 150% or more, 180% or more, or 200% or more. This does not apply to subjects who do not have Bifidobacterium spp.
　また、本明細書において、「腸内菌叢中のコプロコッカス属菌の占有率を増加させる」こととは、本発明の組成物の摂取後の腸内菌叢中のコプロコッカス属菌の占有率が、摂取前と比べて、０．２５％以上、例えば、０．５％以上、０．７５％以上、１％以上、１．２５％以上、１．５％以上又は１．７５％以上増加することを意味する。また、本発明の組成物の摂取後の腸内菌叢中のコプロコッカス属菌の占有率は、摂取前の腸内菌叢中のコプロコッカス属菌の占有率の１２０％以上、１３０％以上、１５０％以上、１８０％以上、又は２００％以上であってもよい。なお、コプロコッカス属菌を有しない対象においては、この限りでない。 Further, in the present specification, "increasing the occupancy rate of Gut microbiota in the intestinal flora" means the occupancy of Gut microbiota in the gut microbiota after ingestion of the composition of the present invention. The rate is 0.25% or more, for example, 0.5% or more, 0.75% or more, 1% or more, 1.25% or more, 1.5% or more or 1.75% or more compared to before ingestion. Means to increase. In addition, the occupancy rate of Gut microbiota in the intestinal flora after ingestion of the composition of the present invention is 120% or more, 130% or more of the occupancy rate of Gut microbiota in the gut microbiota before ingestion. , 150% or more, 180% or more, or 200% or more. This does not apply to subjects who do not have Coccoccus spp.
　さらに、本明細書において、「腸内菌叢中のフソバクテリウム属菌の占有率を減少させる」とは、本発明の組成物の摂取後の腸内菌叢中のフソバクテリウム属菌の占有率が、摂取前と比べて、０．５％以上、例えば、１％以上、１．５％以上、２％以上、２．５％以上、３％以上、３．５％以上又は４％以上減少することを意味する。また、本発明の組成物の摂取後の腸内菌叢中のフソバクテリウム属菌の占有率は、摂取前の腸内菌叢中のフソバクテリウム属菌の占有率の９０％以下、８０％以下、７０％以下、６０％以下、又は５０％以下であってもよい。なお、フソバクテリウム属菌を有しない対象においては、この限りでない。 Further, in the present specification, "reducing the occupancy rate of Fusobacterium in the intestinal flora" means that the occupancy rate of Fusobacterium in the intestinal flora after ingestion of the composition of the present invention is defined as. 0.5% or more, for example, 1% or more, 1.5% or more, 2% or more, 2.5% or more, 3% or more, 3.5% or more or 4% or more decrease compared to before ingestion. Means. The occupancy rate of Fusobacterium in the intestinal flora after ingestion of the composition of the present invention is 90% or less, 80% or less, 70% of the occupancy rate of Fusobacterium in the intestinal flora before ingestion. It may be% or less, 60% or less, or 50% or less. This does not apply to subjects who do not have Fusobacterium spp.
　ここで、腸内菌叢とは、腸内に存在する細菌（腸内細菌）を意味し、検出可能な細菌の全て、例えば、ビフィドバクテリウム属菌、コプロコッカス属菌、フソバクテリウム属菌、クロストリジウム属菌、ドレア属菌、及びオシロスピラ属菌を含む。腸内菌叢の検出は、一般的に知られている方法、又は市販のキットによって行うことができる。一例として、糞便を検体として、本発明の組成物の摂取前及び摂取後の糞便中のＤＮＡを精製し、１６Ｓ　ｒＲＮＡ　Ｖ３－Ｖ４領域を増幅し、次世代シーケンサーＭｉＳｅｑを用いて配列解析を行い、クオリティーフィルタリング後、９７％の相同性でクラスタリングし、ＯＴＵ（ｏｐｅｒａｔｉｏｎａｌ　ｔａｘｏｎｏｍｉｃ　ｕｎｉｔ）に分類する。形成されたＯＴＵの代表配列を完全長１６Ｓ遺伝子データベースに対して照合し、菌種の特定及び構成の解析を行う。最後に、腸内菌叢全菌数を１００％とした場合の各菌、例えばビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率及びフソバクテリウム属菌の占有率を計算する。 Here, the intestinal flora means a bacterium existing in the intestine (intestinal bacterium), and all detectable bacteria, for example, Bifidobacterium spp., Clostridium spp., Fusobacterium spp. Includes Clostridium spp., Drea spp., And Osirospira spp. Detection of gut microbiota can be performed by commonly known methods or commercially available kits. As an example, using feces as a sample, DNA in feces before and after ingestion of the composition of the present invention was purified, 16S rRNA V3-V4 region was amplified, and sequence analysis was performed using the next-generation sequencer MiSeq. After quality filtering, clustering is performed with 97% homology and classified into OTU (operational taxonomy unit). The representative sequence of the formed OTU is collated with the full-length 16S gene database, and the bacterial species are identified and the composition is analyzed. Finally, when the total number of intestinal flora is 100%, the occupancy rate of each bacterium, for example, Bifidobacterium genus, Coprococcus genus, and Fusobacterium genus is calculated.
　本発明の組成物は、治療的又は非治療的用途に使用することができる。また、本発明の組成物は、ヒト、サル、マウス、ラット、ウサギ、イヌ、ネコ、ウマ、ウシ、ブタ等を含む哺乳類動物、好ましくはヒトに対して適用することができる。 The composition of the present invention can be used for therapeutic or non-therapeutic applications. In addition, the composition of the present invention can be applied to mammals including humans, monkeys, mice, rats, rabbits, dogs, cats, horses, cows, pigs and the like, preferably humans.
　本発明の組成物は、腸内菌叢中のビフィドバクテリウム属菌の占有率増加、コプロコッカス属菌の占有率増加、及び、フソバクテリウム属菌の占有率減少により治療、予防若しくは改善に有効である疾患又は症状の治療、予防若しくは改善のために用いることができる。 The composition of the present invention is effective for treatment, prevention or improvement by increasing the occupancy rate of Bifidobacterium spp. In the intestinal flora, increasing the occupancy rate of Coprococcus spp., And decreasing the occupancy rate of Fusobacterium spp. It can be used for the treatment, prevention or amelioration of a disease or symptom.
　ビフィドバクテリウム属菌の占有率増加、コプロコッカス属菌の占有率増加、及び、フソバクテリウム属菌の占有率減少により治療、予防若しくは改善しうる疾患及び症状としては、例えば、炎症性疾患（例えば、潰瘍性大腸炎、クローン病などの炎症性腸疾患）、アレルギー性疾患（例えば、食品アレルギー、花粉症、喘息、アレルギー性鼻炎、薬物アレルギー、アトピー性皮膚炎、ダニアレルギー）、下痢や便秘等の腸疾患、大腸がん、糖尿病、うつ病、歯周病、レミエール症候群、皮膚潰瘍、その他腸内菌共生バランス失調（Ｄｙｓｂｉｏｓｉｓ）に起因すると考えられる疾病（例えば、過敏性腸症候群、小腸細菌異常増殖症（ＳＩＢＯ）、偽膜性大腸炎（クロストリジウム・ディフィシル腸炎）、肥満、アレルギー疾患、自閉症などの精神疾患、多発性硬化症）などが挙げられる。 Diseases and symptoms that can be treated, prevented or ameliorated by increasing the occupancy rate of Bifidobacterium spp., Increasing the occupancy rate of Coprococcus spp., And decreasing the occupancy rate of Fusobacterium spp. , Inflammatory bowel diseases such as ulcerative colitis, Crohn's disease), allergic diseases (eg, food allergies, pollinosis, asthma, allergic rhinitis, drug allergies, atopic dermatitis, tick allergies), diarrhea and constipation, etc. Intestinal diseases, colon cancer, diabetes, depression, periodontal disease, Remière syndrome, skin ulcers, and other diseases thought to be caused by intestinal symbiotic imbalance (Dysbiosis) (eg, hypersensitivity intestinal syndrome, small intestinal bacterial abnormalities) Examples thereof include proliferative disorders (SIBO), pseudomembranous colitis (Crostridium difficile enteritis), obesity, allergic diseases, mental diseases such as autism, and polysclerosis).
　本発明の組成物は、食品組成物、医薬組成物又は医薬部外品であってよく、また、食品、飼料等の添加剤として使用してもよい。 The composition of the present invention may be a food composition, a pharmaceutical composition or a quasi-drug, or may be used as an additive for foods, feeds and the like.
　本発明の組成物は、大建中湯エキスのみからなるものであってよく、大建中湯エキス以外の成分を含んでもよい。本発明の組成物中の大建中湯エキスの配合量は、形態、剤型、症状などに応じて適宜設定することができ、典型的には０．１～１００質量％、好ましくは０．１～９９．９質量％、より好ましは０．１～５０質量％、特に好ましくは０．１～３０質量％とすることができる。 The composition of the present invention may consist only of Daikenchuto extract, and may contain components other than Daikenchuto extract. The blending amount of Daikenchuto extract in the composition of the present invention can be appropriately set according to the form, dosage form, symptoms and the like, and is typically 0.1 to 100% by mass, preferably 0. It can be 1 to 99.9% by mass, more preferably 0.1 to 50% by mass, and particularly preferably 0.1 to 30% by mass.
　本発明の組成物は、その形態を特に問うものではなく、例えば、ゼリー状、粉末状、顆粒状、錠剤状、カプセル状、液状、懸濁液状、乳液状などの製剤形態を有し得る。 The composition of the present invention is not particularly limited in its form, and may have a pharmaceutical form such as jelly, powder, granule, tablet, capsule, liquid, suspension, milky liquid or the like.
　本発明の組成物の摂取（投与）方法としては、好ましくは、経口投与である。また、経口投与以外の投与も可能であり、例えば、本発明の組成物には、腸への効率的な輸送を目的として、基剤が配合されてもよい。当該基剤には、一般的なゲル化剤が用いられ、適度な保存安定性が求められるため、ゼラチン以外のものが好ましい。そのようなゲル化剤としては例えば、カラギーナン、ローカストビーンガム、キサンタンガム、ポリアクリル酸、カロブビーンガムなどが好ましい。 The method for ingesting (administering) the composition of the present invention is preferably oral administration. In addition, administration other than oral administration is also possible. For example, the composition of the present invention may contain a base for the purpose of efficient transportation to the intestine. As the base, a general gelling agent is used, and an appropriate storage stability is required. Therefore, a base other than gelatin is preferable. As such a gelling agent, for example, carrageenan, locust bean gum, xanthan gum, polyacrylic acid, carob bean gum and the like are preferable.
　本発明の食品組成物は、保健、健康維持、増進等を目的とし、また、プレバイオティクスとしての食品組成物であることが好ましく、例えば、健康食品、機能性食品、栄養補助食品、サプリメント、特定保健用食品、栄養機能食品、機能性表示食品、幼児用食品、妊産婦用食品、病者用食品を挙げることができる。 The food composition of the present invention is intended for health, health maintenance, promotion, etc., and is preferably a food composition as prebiotics, for example, health foods, functional foods, nutritional supplements, supplements, etc. Examples include foods for specified health use, foods with nutritional function, foods with functional claims, foods for infants, foods for pregnant women, and foods for the sick.
　食品組成物には、大建中湯エキスの他に、必要に応じて、追加の成分を配合することができる。当該追加の成分として、例えば、複合的な効果を奏することを目的として、機能性を有する食品材料を適宜任意に配合することができる。例えば、大建中湯エキス以外の各種生薬、各種プロバイオティクス、プレバイオティクス、各種オリゴ糖、ビタミン、ミネラル等の栄養成分、その他公知の機能性食品材料を適宜任意に配合することができる。 In addition to Daikenchuto extract, additional ingredients can be added to the food composition as needed. As the additional component, for example, a food material having functionality can be arbitrarily blended for the purpose of exerting a complex effect. For example, various crude drugs other than Daikenchuto extract, various probiotics, prebiotics, various oligosaccharides, vitamins, minerals and other nutritional components, and other known functional food materials can be appropriately blended.
　また、当該追加の成分として、通常の食品に使用される食品原料を適宜任意に配合することができる。例えば、各種一般食材、デンプン、ゼラチン、カルボキシメチルセルロース、アラビアガム、ローカストビーンガム、トラガントガム、カラヤガム、コンニャクグルコマンナン、キサンタンガム、寒天、カラギーナン、ポリアクリル酸、カロブビーンガム、アルギン酸、シクロデキストリン等のゲル化剤をはじめとした基剤、或いは植物油脂、動物油脂、加工油脂、調味料、甘味料、香辛料、着色料、保存料、酸化防止剤、水等を適宜任意に配合することができる。 In addition, as the additional ingredient, food raw materials used in ordinary foods can be arbitrarily blended. For example, various general ingredients, starch, gelatin, carboxymethyl cellulose, Arabic gum, locust bean gum, tragant gum, karaya gum, konjac glucomannan, xanthan gum, agar, carrageenan, polyacrylic acid, carob bean gum, alginic acid, cyclodextrin and other gelling agents. The base, vegetable fats and oils, animal fats and oils, processed fats and oils, seasonings, sweeteners, spices, coloring agents, preservatives, antioxidants, water and the like can be arbitrarily blended.
　食品組成物は、動物（ヒトを含む）が摂取できるあらゆる飲食品を含む。食品組成物の種類は、特に限定されず、例えば、乳製品；発酵食品（ヨーグルト、チーズ等）；飲料類（コーヒー、ジュース、茶飲料のような清涼飲料、炭酸飲料、乳飲料、乳酸菌飲料、乳酸菌入り飲料、ヨーグルト飲料、日本酒、果実酒、洋酒のような酒等）；スプレッド類（カスタードクリーム等）；ペースト類（フルーツペースト等）；洋菓子類（ドーナツ、パイ、シュークリーム、ガム、キャンデー、ゼリー、クッキー、ケーキ、チョコレート、プリン等）；和菓子類（大福、餅、饅頭、カステラ、あんみつ、羊羹等）；氷菓類（アイスクリーム、アイスキャンデー、シャーベット等）；食品類（カレー、牛丼、雑炊、粥、味噌汁、スープ、ミートソース、パスタ、漬物、ジャム等）；調味料類（ドレッシング、旨味調味料、ふりかけ、スープの素等）等が挙げられる。かかる食品は、業務店舗で料理として提供することもでき、また、惣菜、レトルト食品、冷凍食品、その他一般的な食品組成物の包装形態等を取って一般流通形態で提供することもできる。 The food composition includes all foods and drinks that can be ingested by animals (including humans). The type of food composition is not particularly limited, and is, for example, dairy products; fermented foods (yogurt, cheese, etc.); beverages (soft beverages such as coffee, juice, tea beverages, carbonated beverages, dairy beverages, lactic acid bacteria beverages, etc. Beverages containing lactic acid bacteria, yogurt beverages, Japanese liquor, fruit liquor, liquor such as Western liquor); Spreads (custard cream, etc.); Pastes (fruit paste, etc.); Western confectionery (donuts, pies, cream puffs, gum, candy, jelly, etc.) , Cookies, cakes, chocolates, puddings, etc.); Japanese sweets (Daifuku, rice cakes, buns, castella, anmitsu, sheep drinks, etc.); , Porridge, miso soup, soup, meat sauce, pasta, pickles, jam, etc.); Seasonings (dressing, flavor seasoning, sprinkle, soup base, etc.) and the like. Such foods can be provided as dishes at business stores, or can be provided in a general distribution form by taking a prepared food, a retort pouch food, a frozen food, a packaging form of other general food compositions, or the like.
　本発明の食品組成物の製法も特に限定されず、適宜公知の方法に従うことができる。 The method for producing the food composition of the present invention is not particularly limited, and a known method can be appropriately followed.
　食品組成物がサプリメントである場合、その投与単位形態については特に限定されず適宜選択でき、例えば、錠剤、カプセル剤、顆粒剤、液剤、散剤、ゼリー等が挙げられる。 When the food composition is a supplement, the administration unit form thereof is not particularly limited and can be appropriately selected, and examples thereof include tablets, capsules, granules, liquids, powders, and jellies.
　本発明の組成物が医薬組成物及び医薬部外品であってもよく、この場合、大建中湯エキスのみからなるものであってもよく、大建中湯エキスの他に製薬上許容される無毒性の担体、希釈剤若しくは賦形剤とともに、タブレット（素錠、糖衣錠、フィルムコート錠、発泡錠、チュアブル錠、トローチ剤などを含む）、カプセル剤、丸剤、粉末剤（散剤）、細粒剤、顆粒剤、液剤、懸濁液、乳濁液、ゼリー、シロップ、ペーストなどの形態に調製して、医薬製剤又は医薬部外品にすることができる。製薬上許容される無毒性の担体としては、例えば、結合剤、添加剤、香料、緩衝剤、増粘剤、着色剤、安定剤、乳化剤、分散剤、懸濁化剤、防腐剤などが挙げられる。 The composition of the present invention may be a pharmaceutical composition or a non-pharmaceutical product, and in this case, it may consist only of Daikenchuto extract, which is pharmaceutically acceptable in addition to Daikenchuto extract. Tablets (including uncoated tablets, sugar-coated tablets, film-coated tablets, effervescent tablets, chewable tablets, troches, etc.), capsules, pills, powders (powder), along with non-toxic carriers, diluents or excipients. It can be prepared in the form of fine granules, granules, liquids, suspensions, emulsions, jellies, syrups, pastes, etc. to be pharmaceutical preparations or non-pharmaceutical products. Pharmaceutically acceptable non-toxic carriers include, for example, binders, additives, fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives and the like. Will be.
　本発明の医薬組成物及び医薬部外品の投与方法は特に限定されず、例えば、経口投与、直腸投与、経腸投与、口腔内投与、動脈内投与、静脈内投与、経皮投与などにより行うことができる。 The method for administering the pharmaceutical composition and quasi-drug of the present invention is not particularly limited, and is, for example, oral administration, rectal administration, enteral administration, oral administration, intraarterial administration, intravenous administration, transdermal administration, or the like. be able to.
　大建中湯エキスは既に医薬品として販売されているものもあるが、入手容易性の観点より、本発明の組成物は食品組成物であることが好ましい。 Although some Daikenchuto extracts have already been sold as pharmaceuticals, the composition of the present invention is preferably a food composition from the viewpoint of easy availability.
　本発明の食品組成物、医薬組成物、又は医薬部外品には、例えば、腸内菌叢中のビフィドバクテリウム属菌の占有率を増加させる、コプロコッカス属菌の占有率を増加させる、フソバクテリウム属菌の占有率を減少させる、腸内環境を改善する、腸内菌叢中の酪酸産生菌の占有率を拡大する等の表示が付されていてもよい。 The food composition, pharmaceutical composition, or non-pharmaceutical product of the present invention, for example, increases the occupancy rate of Bifidobacterium spp. In the intestinal flora, and increases the occupancy rate of Coprococcus spp. , Decreasing the occupancy rate of Fusobacterium spp., Improving the intestinal environment, increasing the occupancy rate of butyric acid-producing bacteria in the intestinal flora, etc. may be attached.
　包装形態として、一定量を含有できる形態であれば特に限定されず、例えば、袋、包装紙、紙容器、ソフトバック、缶、ボトル、カプセルなどが挙げられる。 The packaging form is not particularly limited as long as it can contain a certain amount, and examples thereof include bags, wrapping paper, paper containers, soft bags, cans, bottles, and capsules.
　本発明は、有効量の大建中湯エキスをこれを必要とする対象に投与することを含む、腸内菌叢中のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム属菌の占有率を減少させる方法を提供する。該方法は、ビフィドバクテリウム属菌の占有率増加、コプロコッカス属菌の占有率増加、及び、フソバクテリウム属菌の占有率減少により治療、予防若しくは改善しうる疾患及び症状の治療、予防又は改善方法であってよい。本発明はまた、有効量の大建中湯エキスの、腸内菌叢中のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム属菌の占有率を減少させるための組成物の製造における使用に提供する。本発明はさらに、腸内菌叢中のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム属菌の占有率を減少させるための有効量の大建中湯エキスの使用を提供する。 The present invention comprises administering an effective amount of Daikenchuto extract to a subject in need thereof, and the occupancy rate of Bifidobacterium spp. And Coprococcus spp. In the intestinal flora. Provided is a method for increasing and reducing the occupancy rate of Fusobacterium spp. The method treats, prevents or ameliorate diseases and conditions that can be treated, prevented or ameliorated by increasing the occupancy rate of Bifidobacterium spp., Increasing the occupancy rate of Coprococcus spp., And decreasing the occupancy rate of Fusobacterium spp. It may be a method. The present invention also increases the occupancy rate of Bifidobacterium and Coprococcus in the intestinal flora of an effective amount of Daikenchuto extract, and also increases the occupancy of Fusobacterium. Provided for use in the manufacture of compositions for reducing. The present invention further increases the occupancy rate of Bifidobacterium spp. And Coprococcus spp. In the intestinal flora, and reduces the occupancy rate of Fusobacterium spp. Provide the use of Nakato extract.
　以下、本発明を更に詳しく説明するため実施例を挙げる。しかし、本発明はこれら実施例等になんら限定されるものではない。 Hereinafter, examples will be given to explain the present invention in more detail. However, the present invention is not limited to these examples and the like.
実施例１　ヒト糞便嫌気培養試験
（組成物の作製）
　市販される花椒（福田龍株式会社製）、御種人参（オタネニンジン；恵遠ジャパン株式会社製）、乾姜（浙江恵松製薬有限公司、中国）を１：１：２の比率で１５ｗ／ｗ％の含水エタノールにて沸騰抽出し、ろ過、濃縮、殺菌を行うことで、大建中湯軟エキスを作製した。花椒１ｇ、御種人参１ｇ、乾姜２ｇに対し１．２５ｇの大建中湯軟エキスを得た。 Example 1 Human fecal anaerobic culture test (preparation of composition)
Commercially available Japanese pepper (manufactured by Ryu Fukuda Co., Ltd.), ginseng (Ginseng; manufactured by Keien Japan Co., Ltd.), and dried ginger (Zhejiang Keimatsu Pharmaceutical Co., Ltd., China) at a ratio of 1: 1: 2 15w / w A soft extract of ginseng was prepared by boiling and extracting with% hydrous ethanol, filtering, concentrating, and sterilizing. 1.25 g of Daikenchuto soft extract was obtained for 1 g of Japanese pepper, 1 g of ginseng, and 2 g of dried ginger.
（ヒト糞便の嫌気培養）
　３０歳以上６０歳未満、喫煙歴なし、６カ月以内の抗菌剤の摂取経験なし、の条件を満たす日本人健常者を糞便ドナーとして募集し、インフォームド・コンセントを取得のうえ、糞便を採取した。当該糞便を、特許文献２に開示の腸内菌叢シミュレーション培養方法より改変を加えた方法、具体的には低級脂肪酸である酪酸を加えずに、また塩酸若しくは水酸化ナトリウムによるｐＨの調整を除きｐＨ範囲６．０～７．０を超えるｐＨ域で嫌気培養し、ヒト腸内細菌叢を再現した。当該嫌気培養には４人のドナー（Ｆ３２（３２歳女性）、Ｆ４２ｂ（４２歳女性）、Ｍ３９（３９歳男性）、Ｍ４１（４１歳男性））から採取した糞便を用い、各糞便を１００ｍＬ容器にて４８時間培養した。大建中湯エキスは培養開始時に各糞便培養器に０．５質量％にて添加した。また、対照群として、大建中湯エキスを添加しない糞便培養器をそれぞれ用意し培養試験を実施した。 (Aerobic culture of human feces)
We recruit healthy Japanese people who meet the conditions of 30 to 60 years old, no smoking history, and no experience of taking antibacterial agents within 6 months as fecal donors, obtain informed consent, and collect feces. did. The stool was modified from the intestinal flora simulation culture method disclosed in Patent Document 2, specifically, without adding buty acid, which is a lower fatty acid, and except for pH adjustment with hydrochloric acid or sodium hydroxide. The human intestinal flora was reproduced by anaerobically culturing in a pH range exceeding the pH range of 6.0 to 7.0. For the anaerobic culture, feces collected from four donors (F32 (32-year-old female), F42b (42-year-old female), M39 (39-year-old male), M41 (41-year-old male)) were used, and each feces was placed in a 100 mL container. Was cultured for 48 hours. Daikenchuto extract was added to each fecal incubator at 0.5% by mass at the start of culturing. In addition, as a control group, fecal incubators to which Daikenchuto extract was not added were prepared and a culture test was conducted.
（腸内菌叢の測定方法）
　培養後の糞便中のＤＮＡを精製し、１６Ｓ　ｒＲＮＡ　Ｖ３－Ｖ４領域を増幅し、次世代シーケンサーＭｉＳｅｑ（イルミナ）を用いて配列解析を行った。クオリティーフィルタリング後、９７％の相同性でクラスタリングし、ＯＴＵ（ｏｐｅｒａｔｉｏｎａｌ　ｔａｘｏｎｏｍｉｃ　ｕｎｉｔ）に分類した。形成されたＯＴＵの代表配列を完全長１６Ｓ遺伝子データベースに対して照合し、菌種の特定・構成の解析を行った。クラスタリングから菌叢組成解析は、ＱＩＩＭＥのパイプラインを用い、完全長１６Ｓ遺伝子データベースはＧｒｅｅｎｇｅｎｅｓを利用した。 (Measuring method of intestinal flora)
DNA in feces after culture was purified, the 16S rRNA V3-V4 region was amplified, and sequence analysis was performed using the next-generation sequencer MiSeq (Illumina). After quality filtering, clustering was performed with 97% homology and classified into OTU (operational taxonomy unit). The representative sequence of the formed OTU was collated against the full-length 16S gene database, and the bacterial species were identified and the composition was analyzed. From clustering to flora composition analysis, the QIIME pipeline was used, and the full-length 16S gene database was Greengenes.
（結果）
　結果を表１に示す。４ドナーの糞便全てにおいて、腸内菌叢全菌数を１００％とした場合のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率が、大建中湯エキス添加群において、対照群（非添加群）と比較して増加した。また、フソバクテリウム属菌を保有する３ドナーの糞便全てにおいて、フソバクテリウム属菌の占有率が、大建中湯エキス添加群において、対照群（非添加群）と比較して減少した。すなわち、大建中湯エキスにより、腸内菌叢中のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム菌の占有率を減少させることができることを確認した。また、データは示していないが、腸内菌叢中の、例えば、クロストリジウム属菌、ドレア属菌、及びオシロスピラ属菌の割合は有意な変化は認められなかった。
Figure JPOXMLDOC01-appb-T000001
 (result)
The results are shown in Table 1. In all the feces of the four donors, the occupancy rate of bifidobacteria and coprococcus spp. When the total number of intestinal flora was 100% was controlled in the Daikenchuto extract-added group. Increased compared to the group (non-additive group). In addition, the occupancy rate of Fusobacterium was reduced in the daikenchuto extract-added group as compared with the control group (non-added group) in all the feces of the three donors carrying Fusobacterium. That is, the daikenchuto extract can increase the occupancy rate of Bifidobacterium spp. And the occupancy rate of Coprococcus spp. In the intestinal flora, and can decrease the occupancy rate of Fusobacterium. confirmed. In addition, although no data are shown, no significant change was observed in the proportions of, for example, Clostridium spp., Drea spp., And Osirospira spp. In the intestinal flora.
Figure JPOXMLDOC01-appb-T000001

Claims (9)

  1. 　有効量の大建中湯エキスを含む、腸内菌叢中のビフィドバクテリウム属菌の占有率及びコプロコッカス属菌の占有率を増加させ、かつ、フソバクテリウム属菌の占有率を減少させるための組成物。 To increase the occupancy of Bifidobacterium and Coprococcus in the intestinal flora, including an effective amount of Daikenchuto extract, and to decrease the occupancy of Fusobacterium. Composition.
  2. 　前記大建中湯エキスが、（１）山椒及び／又は花椒、（２）人参、並びに（３）乾姜からなる原料生薬のエキスである、請求項１に記載の組成物。 The composition according to claim 1, wherein the Daikenchuto extract is an extract of a raw material crude drug consisting of (1) Japanese pepper and / or Japanese pepper, (2) carrot, and (3) dried ginger.
  3. 　前記大建中湯エキスが、原料生薬の、水、エタノール、或いは、水とエタノールとの混合溶媒の抽出エキスである、請求項１又は２に記載の組成物。 The composition according to claim 1 or 2, wherein the Daikenchuto extract is an extract of a crude drug as a raw material, which is an extract of water, ethanol, or a mixed solvent of water and ethanol.
  4. 　前記大建中湯エキスの１日摂取量が０．１～１５ｇである、請求項１～３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 daily intake of the Daikenchuto extract is 0.1 to 15 g.
  5. 　前記大建中湯エキスの１日摂取量が０．１～３ｇである、請求項１～４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 daily intake of the Daikenchuto extract is 0.1 to 3 g.
  6. 　前記大建中湯エキスの原料生薬において、（１）山椒及び／又は花椒の質量を１質量部とした場合、（２）人参が０．２～２．０質量部、（３）乾姜が１．０～３．０質量部である、請求項１～５のいずれか一項に記載の組成物。 In the crude drug used as the raw material for the Daikenchuto extract, when (1) Japanese pepper and / or Chinese pepper is 1 part by mass, (2) 0.2 to 2.0 parts by mass of ginger and (3) dried ginger are used. The composition according to any one of claims 1 to 5, which is 1.0 to 3.0 parts by mass.
  7. 　前記大建中湯エキスの原料生薬において、（１）山椒及び／又は花椒の質量を１質量部とした場合、（２）人参が０．４～１．４質量部、（３）乾姜が１．４～２．４質量部である、請求項１～６のいずれか一項に記載の組成物。 In the crude drug used as the raw material of the Daikenchuto extract, when (1) Japanese pepper and / or Chinese pepper is 1 part by mass, (2) 0.4 to 1.4 parts by mass of ginger and (3) dried ginger are used. The composition according to any one of claims 1 to 6, which is 1.4 to 2.4 parts by mass.
  8. 　前記大建中湯エキスの１日摂取量が、（１）山椒又は花椒０．５～６ｇ、（２）人参０．５～６ｇ、並びに（３）乾姜１～１２ｇからなる原料生薬から得られるエキスに相当する量である、請求項１～７のいずれか一項に記載の組成物。 The daily intake of the Daikenchuto extract is obtained from a crude drug consisting of (1) Japanese pepper or Japanese pepper 0.5 to 6 g, (2) carrot 0.5 to 6 g, and (3) dried ginger 1 to 12 g. The composition according to any one of claims 1 to 7, which is an amount corresponding to the extract to be obtained.
  9. 　食品組成物である、請求項１～８のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 8, which is a food composition.
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