阅读说明：本技术 用于增加肠道菌群中栖粪杆菌占有率的组合物 (Composition for increasing occupancy of coprobacterium inhabitans in intestinal flora ) 是由 山森明弘 佐佐木克典 于 2020-03-04 设计创作，主要内容包括：公开了一种用于增加肠道菌群中栖粪杆菌属细菌占有率的组合物,该组合物包含大建中汤提取物。(Disclosed is a composition for increasing the occupancy of fecal bacteria in the intestinal flora, the composition comprising an extract of DAJIANZHONGTANG.)

1. A composition for increasing the occupancy of coprobacter sp in the intestinal flora, the composition comprising a dajianzhong decoction extract.

2. The composition of claim 1, wherein the extract of DAJIANZHONGTANG is present in a daily intake effective to increase the occupancy of fecal bacteria in the intestinal flora.

3. The composition according to claim 1 or 2, wherein the daikenchun extract is contained in an amount of 0.1-15 g per day.

4. The composition according to claim 1 or 2, wherein the daikenchun extract is contained in an amount of 0.1 to 3.0g per day.

5. The composition according to any one of claims 1 to 4, wherein the mass ratio of the raw medicinal materials used for obtaining the decoction extract in the Chinese rhubarb is prickly ash fruit or prickly ash: ginseng: dried ginger is 1: 0.2-2.0: 1.0 to 3.0.

6. The composition according to any one of claims 1 to 4, wherein the mass ratio of the raw medicinal materials used for obtaining the decoction extract in the Chinese rhubarb is prickly ash fruit or prickly ash: ginseng: dried ginger is 1: 0.4-1.4: 1.4 to 2.4.

7. The composition according to any one of claims 1 to 6, wherein the composition is for use in the treatment, prevention or amelioration of a disease or condition that can be treated, prevented or ameliorated by increasing the occupancy of coprobacter bacteria in the intestinal flora.

8. The composition according to any one of claims 1 to 7, wherein the composition is a food product.

Technical Field

The present invention relates to a composition for increasing the occupancy of coprobacter bacteria in the intestinal flora.

Background

The bacterium belonging to the genus coprobacter is a short-chain fatty acid-producing bacterium that mainly produces butyric acid as a metabolite. Butyric acid has the ability to induce regulatory T cells (tregs), and has been found to have anti-inflammatory and anti-allergic effects. The occupancy of the bacterium belonging to the genus coprinus in the human intestinal flora is as high as several percent, and it is suggested that the reduction of the bacterium belonging to the genus coprinus may be related to crohn's disease and the like (non-patent literature (NPL) 1).

Cocoa (Cacao) has been traditionally known to contribute to an increased occupancy of coprobacter bacteria. For example, patent literature (PTL)1 reports that a processed fat composition containing a high concentration of a digestive tract regulating substance (luminal) derived from cocoa beans significantly increases the occupancy of coprobacter bacteria in the human intestinal flora.

However, cocoa contains theobromine, caffeine, and the like. Because theobromine and caffeine have effects such as bronchodilation, diuresis, and excitement, care should be taken when eating a food with high cocoa content, such as a person sensitive to these ingredients, a person taking a drug such as theophylline, and a pregnant woman.

CITATION LIST

Patent document

Patent document 1: WO2018/056284

Non-patent document

NPL 1: the ISME Journal, 11 months 2017, page 841-852

Disclosure of Invention

Technical problem

It is an object of the present invention to provide a composition for increasing the occupancy of a bacterium of the genus coprophilus.

Means for solving the problems

The present inventors have conducted intensive studies to solve the above problems, and as a result, have found that extract of shigella shimeji decoction (Daikenchuto), which is a raw material of Chinese medicinal materials, can significantly increase the occupancy (%) of the bacteria of the genus coprobacterium in the human intestinal flora.

The present invention has been completed based on the above findings. The present invention provides the following compositions for increasing the occupancy of coprobacter bacteria in the intestinal flora.

Item 1: a composition for increasing the occupancy of fecal bacteria in the intestinal flora, the composition comprising an extract of DAJIANZHONGTANG.

Item 2: the composition of item 1, wherein the extract of DAJIANZHONGTANG is present in a daily intake effective to increase the occupancy of fecal bacteria in the intestinal flora.

Item 3: the composition according to item 1 or 2, wherein the daikenchun extract is contained in an amount of 0.1 to 15g per day.

Item 4: the composition according to item 1 or 2, wherein the extract of DAJIANZHONGTANG is contained in an amount of 0.1-3.0 g per day.

Item 5: the composition according to any one of items 1 to 4, wherein the mass ratio of the raw medicinal materials used for obtaining the decoction extract in the Chinese rhubarb is pepper fruit or pepper: ginseng: dried ginger is 1: 0.2-2.0: 1.0 to 3.0.

Item 6: the composition according to any one of items 1 to 4, wherein the mass ratio of the raw medicinal materials used for obtaining the decoction extract in the Chinese rhubarb is pepper fruit or pepper: ginseng: dried ginger is 1: 0.4-1.4: 1.4 to 2.4.

Item 7: the composition according to any one of items 1 to 6, for use in treating, preventing or ameliorating a disease or condition that can be treated, prevented or ameliorated by increasing the occupancy of coprobacter bacteria in the intestinal flora.

Item 8: the composition according to any one of items 1 to 7, which is a food product.

The present invention also provides the following.

Item 9: a method of increasing the occupancy of coprobacterium bacteria in the gut flora, comprising administering to a mammal in need thereof a composition comprising an extract of dajianzhong decoction.

Item 10: use of a dajianzhong decoction extract for the preparation of a composition for increasing the occupancy of coprobacter bacteria in the intestinal flora.

Item 11: the method according to item 9 or the use according to item 10, wherein the composition comprises a daily intake of the extract of DAJIANZHONGTANG effective to increase the occupancy of fecal bacteria in the intestinal flora.

Item 12: the method according to item 9 or 11, or the use according to item 10 or 11, wherein the composition comprises 0.1 to 15g of daidzein extract per daily intake.

Item 13: the method according to item 9 or 11, or the use according to item 10 or 11, wherein the composition comprises 0.1 to 3.0g of daidzein extract per daily intake.

Item 14: the method according to any one of items 9 and 11 to 13 or the use according to any one of items 10 to 13, wherein the mass ratio of the raw medicinal materials used for obtaining the dajianzhong decoction extract is zanthoxylum fruit or zanthoxylum bungeanum: ginseng: dried ginger is 1: 0.2-2.0: 1.0 to 3.0.

Item 15: the method according to any one of items 9 and 11 to 13 or the use according to any one of items 10 to 13, wherein the mass ratio of the raw medicinal materials used for obtaining the dajianzhong decoction extract is zanthoxylum fruit or zanthoxylum bungeanum: ginseng: dried ginger is 1: 0.4-1.4: 1.4 to 2.4.

Item 16: the method according to any one of items 9 and 11 to 15, or the use according to any one of items 10 to 15, wherein the composition is a food product.

Item 17: the method according to any one of items 9 and 11 to 16, which is a method for treating, preventing or ameliorating a disease or a symptom that can be treated, prevented or ameliorated by increasing the occupancy of coprobacter bacteria in the intestinal flora.

Item 18: the use according to any one of claims 10 to 16, wherein the composition is for the treatment, prevention or amelioration of a disease or condition that can be treated, prevented or ameliorated by increasing the occupancy of coprobacter bacteria in the intestinal flora.

Advantageous effects of the invention

The composition can effectively improve the occupancy rate of the coprobacter bacteria in intestinal flora. In particular, the compositions of the present invention are capable of increasing the occupancy of coprobacterium bacteria in adults without the use of theobromine or caffeine.

The composition of the present invention increases the occupancy of the coprobacter bacteria in the intestinal flora and may be useful for treating, preventing or ameliorating diseases or symptoms that can be treated, prevented or ameliorated by increasing the occupancy of the coprobacter bacteria in the intestinal flora.

Drawings

FIG. 1 is a graph showing the occupancy of the bacteria belonging to the genus Bacillus coprinus in the bacterial flora before and after ingestion of the test food by each subject.

Detailed Description

The present invention is described in detail below.

In this specification, the term "comprising" also includes the meaning of "consisting essentially of … …" and "consisting of … …".

The composition of the present invention is used for increasing the occupancy of coprobacter sp in the intestinal flora, and is characterized by comprising a dajianzhongtang extract.

The coprobacterium bacteria are microorganisms belonging to Clostridium (Clostridium) cluster IV (Clostridium flexibilizatum) subgroup and belonging to the coprobacterium genus. Examples of microorganisms belonging to the genus Bacillus include Clostridium prausnitzii (Faecalibacterium prausnitzii).

The intestinal microbiota (intestinal flora) refers to the bacterial population present in the intestine, also known as the intestinal flora and intestinal flora.

The Dajianzhong Tang is recorded in the Chinese Song Dynasty's medical book "jin Kui Yao L ü e. It is considered to have, for example, an action of enhancing intestinal peristalsis, inhibiting excessive intestinal peristalsis, inhibiting ileus and increasing intestinal blood flow, and an anti-inflammatory action. The dajianzhong decoction is usually obtained by: using a powdery extract of a mixture of raw medicinal materials consisting of 2.0g of prickly ash fruit or prickly ash, 3.0g of ginseng and 5.0g of dried ginger, powdery sugar (maltose ) about 8 times the amount of the extract was mixed therein. The DAJIANZHONG decoction is prepared from fructus Zanthoxyli or fructus Zanthoxyli: ginseng: dried ginger: maltose syrup by weight ratio of 2.0: 3.0: 5.0: 20 by mass ratio.

In the present specification, the term "extract of DAJIANZHONGTANG" refers to an extract of a mixture of raw medicinal materials without containing cerealose. However, the extract of the decoction of DAJIANZHONG contained in the composition of the present invention may be in the form of the extract itself or in the form of a mixture of the extract and maltose.

The composition of the present invention may consist of only the extract of dajianzhong decoction. Alternatively, the composition of the present invention may comprise other components in addition to the daikenchun extract. The content of the dajianzhong decoction extract in the composition of the invention can be properly set according to the composition, the dosage form, the symptoms and the like. When other ingredients are contained, the proportion of the dajianzhong decoction extract in the composition of the present invention is not particularly limited; it is usually, for example, 0.1 to 99.9 mass%, preferably 1 to 50 mass%, and more preferably 4 to 30 mass%.

The composition of the invention may be in any form, for example in the form of a gel, powder, granule, tablet, capsule, liquid, suspension or emulsion.

The compositions of the present invention are preferably administered orally. Administration methods other than oral administration are also suitable. For example, a base may be incorporated into the compositions of the present invention for the purpose of effective transport to the intestine. The base may be a general purpose gelling agent. Gelling agents other than gelatin are preferred because of the need for adequate storage stability. Examples of such gelling agents include carrageenan, locust bean gum, xanthan gum, polyacrylic acid, and carob bean gum.

In the present invention, the phrase "increasing the occupancy of coprobacterium bacteria in the intestinal flora" means: the occupancy of the enterobacteria by the copribacteria increases after ingestion or administration of, for example, 1% or more, 2% or more, 3% or more, 4% or more, 5% or more, 6% or more, 7% or more, 8% or more, 9% or more, or 10% or more of the composition of the present invention, as compared to before ingestion or administration.

The compositions of the invention may be used in therapeutic or non-therapeutic applications. Furthermore, the compositions of the present invention are particularly suitable for mammals including humans (e.g., humans, monkeys, mice, rats, rabbits, dogs, cats, horses, cows, and pigs; preferably humans).

The composition of the present invention can be used for treating, preventing or ameliorating diseases or symptoms which can be effectively treated, prevented or ameliorated by increasing the occupancy of coprobacter bacteria in the intestinal flora.

Examples of diseases and symptoms that can be treated, prevented, or ameliorated by increasing the occupancy of coprobacter bacteria include inflammatory diseases (e.g., ulcerative colitis, crohn's disease, and other inflammatory bowel diseases), allergic diseases (e.g., food allergy, hay fever, asthma, allergic rhinitis, drug allergy, atopic dermatitis, and mite allergy), and diseases believed to be caused by dysbiosis (e.g., crohn's disease, inflammatory bowel disease, irritable bowel syndrome, Small Intestine Bacterial Overgrowth (SIBO), pseudomembranous enteritis (clostridium difficile colitis), colorectal cancer, antibiotic-induced diarrhea, liver diseases such as Alcoholic Steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH), type 2 diabetes, obesity, allergic diseases, psychiatric disorders such as autism, multiple sclerosis).

The composition of the present invention can be used as food, medicine, quasi-drug (quasi-drug), feed, etc. The composition of the present invention also includes the meaning of additives for foods, medicines, quasi drugs, feeds, and the like.

In the present specification, the term "food" also includes the meanings of foods and drinks for the purpose of health, wellness, health promotion and the like (for example, health foods, functional foods, dietary supplements, foods for specific health uses, foods having a nutritional function or foods having a functional declaration), infant foods, foods for pregnant and nursing women, foods for patients and the like.

While the extract of DAJIANZHONG decoction can be used directly in food, other components can be added as required.

Food products include any food and beverage that can be consumed by animals, including humans. The kind of the food is not particularly limited. Examples include dairy products; fermented food products (e.g., yogurt and cheese); beverages (soft drinks such as coffee, fruit juice and tea beverages; carbonated beverages; milk beverages; lactic acid bacteria-containing beverages; yogurt beverages; and alcoholic beverages such as Japanese wine, fruit wine and imported wine); spreads (e.g., custards); pastes (e.g., fruit pastes); western-style confections (e.g., donuts, pies, puffs of cream, chewing gum, candies, jellies, cookies, cakes, chocolates, and puddings); japanese desserts (e.g., Dafu, mochi, steamed bun (manju), Nakazaki cake, sweet bean ice (anmitsu), and sheep soup); frozen desserts (e.g. ice cream, popsicles and water ices); food products (e.g., curry, Regen, porridge, miso soup, meat paste, pasta, sauerkraut, and jam); and seasonings (e.g., seasonings, odorants, rice seasonings, and soup bases).

The method for producing the food is not particularly limited, and a known method can be suitably used.

The dosage unit form when the food is used as a supplement is not particularly limited and may be appropriately selected. Examples include tablets, capsules, granules, liquids, sprays and gels.

The amount of food to be ingested can be appropriately set according to various conditions such as the weight, age, sex, and symptoms of the person who ingests the food. The daily intake of the daikenchun extract is, for example, as described later.

For preparing medicines and quasi drugs, the extract of DAJIANZHONGTANG can be used directly. Alternatively, the daikenchuto extract may be used together with pharmaceutically acceptable non-toxic carriers, diluents or excipients to obtain pharmaceutical preparations, which are, for example, in the form of tablets (e.g., uncoated tablets, sugar-coated tablets, film-coated tablets, foam tablets, chewable tablets and lozenges), capsules, pills, powders (sprays), fine granules, liquids, suspensions, emulsions, jellies, syrups and pastes. Examples of pharmaceutically acceptable non-toxic carriers include binders, additives, flavoring agents, buffers, thickening agents, coloring agents, stabilizing agents, emulsifying agents, dispersing agents, suspending agents, and preservatives.

The method of administration of the drug and quasi-drug is not particularly limited. Examples include oral, rectal, enteral, buccal, intraarterial, intravenous and transdermal administration.

The dose of the drug or quasi-drug can be determined appropriately according to various conditions such as the body weight, age, sex, and symptoms of the patient. For example, the daily dose of the extract of DAJIANZHONG decoction will be described later.

Several of the Dajianzhong decoction extracts have been marketed as drugs. However, the composition of the present invention is preferably used as a food from the viewpoint of availability.

Foods, pharmaceuticals, quasi drugs, etc. can be labeled, for example, for increasing the occupancy of coprobacter bacteria in the intestinal flora or for expanding the occupancy of butyric acid-producing bacteria in the intestinal flora.

The compositions of the present invention may also be used in combination with other compositions. For example, the use of the composition of the present invention in combination with materials and compositions expected to exhibit an effect of increasing the occupancy of coprobacter bacteria can further enhance the effect of increasing the occupancy of coprobacter bacteria in the intestinal flora.

In the composition of the present invention, the daikenchun extract must be dosed in a proper amount because an excessively high dose may cause diarrhea, and an excessively low dose may not achieve the intended effect. The daily dose (daily intake) of the Dajianzhong decoction extract is preferably 0.1-15 g of the extract, and the extract is 0.5-6 g of pepper fruits or pepper, 0.5-6 g of ginseng and 1-12 g of dried ginger (raw medicinal materials); more preferably 0.5-6 g of extract, wherein the extract is the extract of 0.5-2 g of pepper, 0.5-2 g of ginseng and 1-4 g of dried ginger; still more preferably 1 to 2g of an extract of 1 to 1.5g of Zanthoxylum bungeanum, 1 to 1.5g of Panax ginseng and 1.5 to 2.5g of dried ginger. The dose is not limited to once daily but may be divided into multiple daily doses.

The mass ratio of the raw medicinal materials for obtaining the extract of the jianzhong decoction contained in the composition is preferably selected from Chinese prickly ash fruits or Chinese prickly ash: ginseng: dried ginger is 1: 0.2-2.0: 1.0 to 3.0, and more preferably 1: 0.4-1.4: 1.4 to 2.4, and more preferably 1: 0.6-1.2: 1.6 to 2.2.

The results of the following examples demonstrate that the composition of the present invention can be taken continuously for 7 days and that the occupancy of the genus coprophilus increases after 7 days. Therefore, the composition of the present invention is preferably ingested continuously for 1 week or more, more preferably 2 weeks or more, and further preferably 3 weeks or more.

The DAJIANZHONG decoction promotes intestinal peristalsis, which can cause rumble in stomach or gas to pass through after ingestion. Therefore, ingestion is preferably performed before bedtime. As shown in the examples described below, ingestion before sleep showed practical effects.

The composition of the present invention may comprise a daily intake of the extract of dajianzhong decoction effective to increase the occupancy of the enterobacteria by the coprophilus sp. In such a case, the compositions of the present invention may be packaged to provide an effective daily intake. The packaging form can be single package or multi-package, as long as the effective daily intake can be provided. When the daily effective intake amount is divided into a plurality of packages, the plurality of packages containing the daily effective intake amount may be used as a group. For example, the daily effective intake amount of the extract of DAJIANZHONG decoction is, for example, 0.1-15 g, preferably 0.1-3.0 g, and more preferably 0.5-2.0 g.

The packaging form is not particularly limited as long as a predetermined amount of the extract can be contained. Examples include bags, wrappers, paper containers, soft packets, cans, bottles and capsules.

The composition can effectively improve the occupancy rate of the coprobacter bacteria in intestinal flora. In particular, the composition of the present invention can increase the occupancy of the coprobacterium bacteria in the human body in a short time without using theobromine or caffeine. In addition, the composition of the present invention increases the occupancy of the coprobacter bacteria in the intestinal flora, and can contribute to the treatment, prevention, or amelioration of diseases or symptoms that can be treated, prevented, or ameliorated by increasing the occupancy of the coprobacter bacteria in the intestinal flora.

Examples

The present invention is described in more detail below with reference to examples. However, the present invention is not limited to these examples and the like.

Human body study

Preparation of the composition

Commercially available zanthoxylum bungeanum, asian ginseng and dried ginger were used at a ratio of 1: 1: 2, extracting the Dajianzhongtang extract by a known method. Then, 1.25g of the obtained extract, 2.6g of syrup, 0.085g of ethanol, and 0.565g of purified water were mixed to obtain 4.5g of a composition (daily intake).

Human body study

5 healthy subjects over 20 years and under 60 years are selected and the composition is taken before sleep on days 1 to 7. The composition can be administered simultaneously with water or hot water. Occupancy in the flora was measured the day before ingestion of the composition (day 0) and the next morning after 7 days of ingestion (day 8).

Lifestyle during testing

Subjects were instructed to live as usual during the test and to comply with the following restrictions.

Without drastic changes in the eating habits (quantity and content of food), without excessively strict restrictions on diet and overeating, which would deviate considerably from daily life.

Avoiding a large variation in the usual alcohol consumption; however, drinking is not generally limited.

-avoiding as far as possible any major alterations to life before fecal collection one week after completion of ingestion.

Method for measuring flora

DNA in feces was purified and the 16S rRNA V1-V2 region was amplified for sequence analysis using a MiSeq Next Generation sequencer (Illumina). After mass filtering, 10,000 reads were randomly selected from each sample, clustered at 97% homology, and classified as Operation Taxonomic Units (OTUs). Representative sequences of OTUs formed were compiled from the full-length 16S gene database to identify species and analyze their composition. The QIIME pipeline was used for the process from clustering to bacterial flora composition analysis, while Greengenes was used for the full-length 16S gene database.

Reference material:

QIIME: nat Methods, 5 months 2010; phase 7, volume 5: page 335-: 10.1038/nmeth.f.303, electronic version: 2010, 4 and 11 days.

Greengenes: applied and Environmental Microbiology, 2006, month 7, volume 72, phase 7, pages 5069-5072, DOI: 10.1128/AEM.03006-05

Results

The results are shown in table 1 and fig. 1. In the intestinal flora of the subjects (genus level), the occupancy of 4 copromous bacteria was increased by 2% or more in 5 subjects in the test food intake group after intake (day 8) compared to before intake (day 0), and the total number of bacteria in the intestinal flora was 100% (table 1, fig. 1).

TABLE 1