CN111743952A

CN111743952A - Use of rehmanniae radix in regulating intestinal microorganism

Info

Publication number: CN111743952A
Application number: CN201910241991.5A
Authority: CN
Inventors: 魏来
Original assignee: Zhuhai Qiwei Bio Technology Ltd
Current assignee: Zhuhai Qiwei Bio Technology Ltd
Priority date: 2019-03-28
Filing date: 2019-03-28
Publication date: 2020-10-09

Abstract

The invention provides an application of radix rehmanniae in regulating intestinal microorganisms and an application of the radix rehmanniae in preparing a medicament, wherein the medicament is a medicament for treating diseases related to intestinal microorganism disorder.

Description

Use of rehmanniae radix in regulating intestinal microorganism

Technical Field

The invention relates to the field of medical health care, in particular to application of radix rehmanniae and a composition containing the radix rehmanniae in improving and regulating intestinal microorganisms.

Background

A large number of microorganisms live in the human body, and particularly 1000-1150 kinds of bacteria in the intestinal tract of the human body, about 100 trillion, are the most important 'endogenous environmental factors' of the human body, and the number of the bacteria is about 10 times of the number of the cells of the human body. Under normal conditions, the intestinal microorganisms are in a dynamic equilibrium ecological environment, the normal flora not only plays an irreplaceable role in digestion, immunity and virus resistance, but also the change of the intestinal microorganisms has a very close relationship with the health of the body or the occurrence of diseases, particularly some chronic diseases. In the modern social environment, people have high working strength and high living pressure, and the human body is in various stress states for a long time, so that the intestinal microorganisms are often disordered and are shown as abnormal changes of the types, the quantities, the proportions and the biological characteristics of the intestinal microorganisms. Dysbacteriosis, in turn, impairs the barrier function of the intestinal tract by affecting the absorption of nutrients by the body, further aggravating the disease and creating a vicious cycle. Studies have confirmed that the onset of various diseases in the human body, such as chronic diarrhea, constipation, obesity, food allergy, pancreatitis, liver injury, intestinal inflammation, irritable bowel syndrome, digestive tract ulcers, diabetes, Crohn's disease, cardiovascular diseases, tumors, and the like, are closely related to intestinal microorganisms. Although it is not clear whether the metabolic disease is caused by a change in the intestinal microbial flora or caused by a change in the intestinal microbial flora, it is certain that: by changing the composition of the intestinal microbial flora, the health of a human body is influenced, and meanwhile, the intestinal microbial flora can also provide help for treating certain diseases. Currently, gut microbiota have been considered as potential therapeutic targets for a variety of diseases.

Patent document CN108289917A discloses a method of treating an individual with a dysbiosis, comprising determining a first metabolic profile of the gut microbiome of the individual with the dysbiosis, changing the first metabolic profile of the gut microbiome of the individual to a second metabolic profile by administering a fecal bacterial community to the individual.

Patent document CN106620189A provides a method for improving intestinal microbial structure, and its application in the process of preparing medicines, nutraceuticals, health products, foods, beverages, etc. The invention finds out intestinal bacteria groups closely related to host metabolism by adopting a high-throughput sequencing technology and a multivariate statistical method, for example, bacteria producing short-chain fatty acids in intestinal tracts are mostly beneficial bacteria, and the intestinal bacteria can play roles in resisting inflammation, protecting intestinal barrier function, regulating human metabolism and immunity and the like by increasing the content of the short-chain fatty acids in the intestinal tracts. Short chain fatty acid producing bacteria include blautia, Allobaculum, prevotella, bacteroides or Butyricimonas. Most of the bacteria producing endotoxin in the intestinal tract are harmful bacteria, and the bacteria can cause inflammation, damage the intestinal barrier function, cause metabolism and immune disorder of human bodies and the like by increasing the content of the endotoxin in the intestinal tract. Endotoxin-producing bacteria include bacteria of the phylum proteobacteria.

The beneficial gut bacteria discovered by scientists to date fall into three general categories, which include: lactobacillus species (e.g., lactobacillus acidophilus, lactobacillus casei, lactobacillus jensenii, lactobacillus raman, etc.); bifidobacterium (such as Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium ovorans, Bifidobacterium thermophilum, etc.); gram-positive cocci (e.g. faecal streptococci, lactococcus, intermediate streptococci, etc.).

The human biology is composed of two parts, the human genome and the human microbiome, wherein the change of the human genome is extremely difficult, but the change of the microbial composition in the human intestinal tract is relatively easy. At present, high-calorie diet and fast-paced life cause intestinal microorganism disorder of a part of people, most people can select diet adjustment unless emergency occurs, and researches show that some traditional Chinese medicines and some food with homology of medicine and food can adjust intestinal microorganisms of human bodies or animals. For example, patent document CN105596445A relates to the use of cortex moutan and radix paeoniae rubra in regulating intestinal microorganisms, and the inventor finds that the cortex moutan and radix paeoniae rubra can not only regulate intestinal microorganisms, but also have no side effect, and can be taken for a long time. For another example, patent document CN102987383B discloses an application of a dendrobium officinale-loquat nutritional drug in intestinal microorganism regulation, wherein the nutritional drug has the effects of regulating the intestinal flora structure and improving the internal environment of the intestinal tract. Patent document CN106038870A discloses a composition for regulating intestinal microbial flora and a preparation method thereof, wherein the composition comprises probiotics, saccharides and traditional Chinese medicines (rhizoma atractylodis, hawthorn, radix puerariae and the like), and the composition promotes the propagation of the probiotics, inhibits the propagation of harmful bacteria, and achieves the effect of regulating the intestinal flora.

Radix rehmanniae (Rehmannia glutinosa Libosch) is sweet in taste and cold in nature. It enters heart, liver and kidney meridians. Clear heat and cool blood, nourish yin, promote the production of body fluid. The dried rehmannia root mainly comprises B-sitosterol, mannitol, a small amount of stigmasterol, a small amount of Campesterol (Cammesterol), and also comprises lutein (Rehmannin), alkaloid, fatty acid, Catalpol (Catalpol), glucose and 0.0053% of vitamin A substances; the root also contains stachyose, 4.2% arginine and 3.0% r-threonine. Rhizome of rehmannia glutinosa libosch also contains mannitol, stachyose, 0.11% of catalpol, sucrose, 4.2% of arginine, and 3.0% of gamma-threonine.

In the prior art, there is a certain research on the regulation of intestinal microorganisms by the habitat, such as:

patent document CN109247367A discloses a biscuit for improving intestinal nutrition based on homology of medicine and food and a preparation method thereof, wherein traditional Chinese medicine extracts are added into the biscuit, so that the microecological balance of intestinal tracts can be improved from multiple aspects, the intestinal tract power function is improved, and the microbial barrier function of the intestinal tracts is enhanced. Wherein the Chinese medicinal extract is selected from Ganoderma, radix rehmanniae, Scutellariae radix, Raphani semen, etc. Patent document CN108524749A discloses a traditional Chinese medicine composition for improving the distribution of intestinal flora, which comprises radix rehmanniae, poria cocos and radix asparagi, and the traditional Chinese medicine composition can increase the ratio of firmicutes to bacteroidetes, promote the secretion of intestinal short-chain fatty acids, and inhibit inflammatory reaction. However, none of the above prior arts discloses a specific species regulated by the habitat, and in order to compensate for this defect, the inventors of the present invention made relevant studies on the habitat regulation of specific species in the intestinal tract.

Disclosure of Invention

The inventor finds that the radix rehmanniae can obviously improve the quantity of beneficial bacteria in the intestinal tract, inhibit the quantity of harmful bacteria and regulate intestinal microorganisms.

Accordingly, it is an object of the present invention to provide a use of rehmanniae radix or a composition comprising the same for modulating intestinal microorganisms. It is a further object of the present invention to provide the use of rehmanniae radix or a composition comprising rehmanniae radix for the manufacture of a medicament for the treatment of a disease associated with an intestinal disorder.

In a first aspect of the invention, there is provided the use of rehmannia glutinosa for modulating gut microbiota.

Preferably, the radix rehmanniae can be fresh rehmannia, dry rehmannia or prepared rehmannia root. The rhizome of rehmannia mainly contains B-sitosterol, mannitol, a small amount of stigmasterol, a trace amount of Campesterol (Campesol), and also contains lutein (Rehmannin), alkaloid, fatty acid, catalpol, glucose and vitamin A substances; the root contains stachyose, arginine and gamma-threonine. Rhizome of HUAIQINGDIHUANG also contains mannitol, stachyose, catalpol, sucrose, arginine, and gamma-threonine.

Preferably, the intestinal microorganisms include one or a combination of two or more of bacteria, archaea, prokaryotes or viruses.

According to the use of a habitat for modulating gut microorganisms selected from one or a combination of two or more of the genera Lactobacillus (Lactobacillus), Bacteroides (Bacteroides), Streptococcus (Streptococcus), food gluten (victivvallales), Ruminococcus (Ruminococcus), flavobacterium (flavonifroror), oscillatorius (Oscillibacter), clostridium (clostridium), enteromonas (intestinomonas), fretibacillus, cloacibaccillus, adlerreutzia or ethanologenic bacillus (ethanologens), the regulation of gut microorganisms is a selective increase of the number of bacteria in the gut.

Preferably, the gut modulating microorganism is one or a combination of two or more selected from the group consisting of Streptococcus (Streptococcus), food gluten (Victivallales), Ruminococcus (Ruminococcus), flavobacterium (flavobacterium), oscillatoria (Oscillibacter), clostridium (clostridium), enteromonas (intestinomonas), Fretibacterium, cloacibaccillus, adlereutzia or ethanologens (ethanogenins) selectively increasing the number of bacteria in the gut.

In a specific embodiment of the invention, the modulating of the gut microorganism is a selective increase in the number of bacteria in the gut selected from one or a combination of Lactobacillus mucosae, Bacillus uniflora, Lactobacillus amylovorus, Lactobacillus johnsonii, Streptococcus garlicus, Streptococcus infantarius, Victivalla bacterium CCUG 44730, Ruminococcus ampanifera, Flavonibacter platucii, Oscilobacter sp.PEA192, Clostridium bacterium CCNA10, Oscilobacter valigenes, Intestimonbacillus butyricum, Fritibacter fascicularis, Streptococcus faecalis, Clostridium sporogenes, Lactobacillus acidophilus, or a combination thereof.

According to the use of a habitat for modulating gut microorganisms, which are selective in suppressing the number of bacteria in the gut, selected from one or a combination of two or more of Prevotella (Prevotella), Escherichia (Escherichia), Porphyromonas (Porphyromonas), helicobacter (Campybacter), Vibrio butyricum (Anterostipes), Bacteroides (Bacteroides), Lactobacillus (Lactobacillus), Shigella (Shigella), Treponema (Treponema) or Eubacterium (Eubacterium).

Preferably, the intestinal microorganisms are regulated to selectively inhibit the number of intestinal bacteria selected from one or a combination of two or more of Prevotella (Prevotella), Escherichia (Escherichia), Porphyromonas (Porphyromonas), helicobacter (Campybacter), Vibrio butyricum (Aerostipes), Shigella (Shigella), Treponema (Treponema) or Eubacterium (Eubacterium).

IN one embodiment of the invention, the modulating gut microorganism is a selective inhibition of the amount of a bacterium IN the gut selected from the group consisting of Prevotella enoeca, Prevotella fusca, Prevotella bivia, Prevotella jejuni, Escherichia albertii, Porphyromonas asacharolytica, Campylobacter jejuni, Prevotella ruminicola, Anaerothrips hadrus, Bacteroides coccus ciosus, Prevotella sp.

According to the use of the radix rehmanniae in regulating the intestinal microorganisms, the intestinal microorganisms are selectively inhibiting the number of viruses in the intestinal tract, and the viruses are staphylococcus phage (staphylococcus phage).

In one embodiment of the present invention, the modulating of the gut microorganism is a selective inhibition of the amount of a virus in the gut, said virus being Staphylococcus phase andedra.

According to the use of the dried rehmannia root for modulating gut microbes, the gut microbes are selectively increased in the number of archaea in the gut, and the archaea are selected from the group consisting of methanobrevibacterium (methanobacter) and/or methanococcus (Methanosphaera).

In one embodiment of the invention, the modulating gut microbiome is a selective increase in the number of archaea in the gut selected from methanobacterioter smithii and/or Methanosphaerastadtmanae.

According to the use of the biomass in the modulation of gut microbiota, said modulation being the selective increase in the number of protozoa in the gut, said protozoa being blastocysts (blastocysts).

In one embodiment of the invention, the regulation of gut microbiota is a selective increase of the number of protozoa in the gut selected from the group consisting of one or a combination of more than two of Blastocystis sp.subtype 3, blastocystomynis, Blastocystis sp.subtype 1 and blastocysts sp.subtype 2.

In a second aspect of the invention, there is provided use of rehmannia glutinosa libosch for the manufacture of a medicament for the treatment of a condition associated with a disturbed intestinal flora.

Preferably, the intestinal flora comprises one or a combination of more than two of bacteria, archaea, prokaryotes or viruses.

Preferably, the disease associated with disturbance of the intestinal flora is selected from one or a combination of more than two of chronic diarrhea, constipation, obesity, food allergy, pancreatitis, liver injury, intestinal inflammation, irritable bowel syndrome, digestive tract ulcer, kidney stone, diabetes, rheumatoid arthritis, behcet's disease, cardiovascular disease, cerebrovascular disease, tumor, paralysis, eye disease, multiple sclerosis, ankylosing spondylitis, parkinson's disease, anxiety, autism, depression or chronic fatigue.

In a third aspect of the invention, there is provided the use of a composition comprising rehmannia glutinosa for modulating gut microbiota.

Preferably, the gut-modulating microorganism is one or a combination of two or more selected from the group consisting of Lactobacillus (Lactobacillus), Bacteroides (Bacteroides), Streptococcus (Streptococcus), food millet (victvivalales), Ruminococcus (Ruminococcus), flavobacterium (flavobacterium), dithiabacter (Oscillibacter), clostridium (clostridium), enteromonas (intestinomonas), Fretibacterium, Cloacibacillus, adlercutzia or ethanologens (ethanogenins) selectively increasing the number of bacteria in the gut.

More preferably, the gut-modulating microorganism is one or a combination of two or more of Streptococcus (Streptococcus), food gluten (Victivallales), Ruminococcus (Ruminococcus), flavobacterium (flavobacterium), oscillatoria (Oscillibacter), clostridium (clostridium), enteromonas (intestinomonas), Fretibacterium, cloacicillus, adlercutzia or ethanologenic bacillus (ethanogenens) that selectively increases the number of bacteria in the gut.

Preferably, the intestinal microorganisms are regulated to selectively inhibit the number of intestinal bacteria selected from one or a combination of two or more of Prevotella (Prevotella), Escherichia (Escherichia), Porphyromonas (Porphyromonas), helicobacter (Camptobacter), Vibrio butyricum (Aerostipes), Bacteroides (Bacteroides), Lactobacillus (Lactobacillus), Shigella (Shigella), Treponema (Treponema) or Eubacterium (Eubacterium).

More preferably, the intestinal microorganisms are regulated to selectively inhibit the number of intestinal bacteria selected from one or a combination of two or more of Prevotella (Prevotella), Escherichia (Escherichia), Porphyromonas (Porphyromonas), helicobacter (Campylobacter), Vibrio butyricum (Aerostipes), Shigella (Shigella), Treponema (Treponema), or Eubacterium (Eubacterium).

Preferably, the intestinal microorganism is regulated to selectively inhibit the amount of viruses in the intestinal tract, and the viruses are Staphylococcus phage (Staphylococcus phage).

Preferably, the intestinal microorganism is regulated to selectively increase the number of archaea in the intestinal tract, and the archaea is selected from the genus Methanobrevibacter and/or Methanococcus (Methanophaga).

Preferably, the intestinal microorganism is regulated to selectively increase the number of protozoa in the intestinal tract, such as blastocysts (blastocysts).

Preferably, the composition containing the radix rehmanniae is the combination of the radix rehmanniae and one or more than two of qi tonics, blood tonics, yin tonics, cold phlegm warming and resolving medicines, blood cooling and bleeding stopping medicines, blood stasis removing and bleeding stopping medicines, water-disinhibiting and swelling-subsiding medicines, heat-clearing and blood-cooling medicines or intestinal bacteria.

Wherein the qi tonics are selected from: one or more of radix Ginseng, radix Panacis Quinquefolii, radix Codonopsis, radix Pseudostellariae, radix astragali, rhizoma Atractylodis Macrocephalae, rhizoma Dioscoreae, semen lablab album, radix Glycyrrhizae, fructus Jujubae, radix Et caulis Acanthopanacis Senticosi, gynostemma pentaphyllum, radix Rhodiolae, fructus Hippophae, maltose, and Mel; the blood-tonifying agent is selected from: one or more of radix Angelicae sinensis, radix Paeoniae alba, colla Corii Asini, Polygoni Multiflori radix, arillus longan or fructus Broussonetiae; the yin-tonifying medicine is selected from: radix Glehniae, radix Adenophorae, Bulbus Lilii, radix Ophiopogonis, radix asparagi, herba Dendrobii, rhizoma Polygonati Odorati, rhizoma Polygonati, radix Changii, fructus Lycii, Ecliptae herba, fructus Ligustri Lucidi, Mori fructus, semen Sesami Niger, carapax et Plastrum Testudinis, carapax Trionycis, Tremella, nidus Collocaliae or fish glue; the cold-phlegm warming and resolving medicine is selected from: one or more of rhizoma Pinelliae, rhizoma arisaematis, semen Sinapis Albae, fructus Gleditsiae Abnormalis, Inulae flos, Bulbus Fritillariae Cirrhosae, fructus Trichosanthis, caulis Bambusae in Taenia, succus Bambusae, concretio silicea Bambusae seu Schizostachyi, radix Peucedani, radix Platycodi or semen Scaphii Lychnophori; the blood-cooling hemostatics are selected from: one or more of herba Cephalanoploris, herba seu radix Cirsii Japonici, radix Sangusorbae, flos Sophorae Immaturus, folium Platycladi, lalang grass rhizome, radix Curcumae and radix Boehmeriae; the stasis-removing hemostatics are selected from: one or more of Notoginseng radix, radix Rubiae, pollen Typhae, Ophicalcitum, lignum Dalbergiae Odoriferae and crinis Carbonisatus; the diuresis-inducing and edema-alleviating drug is selected from: poria, Coicis semen, Polyporus, Alismatis rhizoma, exocarpium Benincase, stigma Maydis, bottle gourd, cortex Periplocae Radicis, semen Hoveniae, herba Euphorbiae Helioscopiae, Gryllotalpa or herba Capsellae; the heat-clearing and blood-cooling medicine is selected from: charred radix Et rhizoma Rhei, radix scrophulariae, cortex moutan, radix Paeoniae Rubra, radix Arnebiae, cornu Bubali, or herba Rabdosiae Lophanthoidis; the enteric bacteria are selected from one or more of Lactobacillus (Lactobacillus), Bacteroides (Bacteroides), Streptococcus (Streptococcus), food Valeriella (Victivallales), Ruminococcus (Ruminococcus), Flavobacterium (FlavoninFremonorus), Oscillatoria (Oscilobacter), Clostridium (Clostridium), Enteromomonas (Intestimonas), Fritibacter, Clinaciae, Adlercutzia, ethanologen (Ethanoligenins), Methanobacter (Methanobacter), Methanococcus (Methanophaga) or Blastocystis (Blastocystis).

More preferably, the blood-tonifying medicine is angelica.

Further preferably, the qi-tonifying drug is astragalus.

Preferably, the yin-tonifying medicine is rhizoma polygonati.

Preferably, the enteric bacteria are selected from the group consisting of Lactobacillus mucosae, Bacillus uniF, Lactobacillus amylovorus, Lactobacillus johnsonii, Streptococcus garleolyticus, Streptococcus infantarius, Victivalles bacterium CCUG 44730, Saccharomyces cerevisiae, Flavonibacter platinii, Escherichia coli PEA192, Clostridium bacterium CCNA10, Escherichia coli, Intestimmunismuthylacterium, Clostridium fatiguum, Streptococcus faecalis, Streptomyces equorubium, Clostridium sporogenes, Lactobacillus sporogenes.

In a fourth aspect of the invention, there is provided the use of a composition comprising rehmannia glutinosa libosch for the manufacture of a medicament for the treatment of a condition associated with a disturbed intestinal flora.

More preferably, the blood-tonifying medicine is angelica.

Further preferably, the qi-tonifying drug is astragalus.

Preferably, the yin-tonifying medicine is rhizoma polygonati.

Preferably, the intestinal flora is selected from one or a combination of more than two of bacteria, archaea, protozoa or viruses.

The composition containing the radix rehmanniae has the ratio of the portion of the radix rehmanniae to one or more than two of qi tonics, blood tonics, yin tonics, cold phlegm warming and resolving medicines, blood cooling and bleeding stopping medicines, blood stasis removing and bleeding stopping medicines, diuresis inducing and swelling reducing medicines, heat clearing and blood cooling medicines or intestinal bacteria of 1-99: 99-1.

Preferably, the composition containing radix rehmanniae further comprises pharmaceutically acceptable auxiliary materials selected from: carrier, diluent, adhesive, lubricant and wetting agent.

Preferably, the formulation of the composition comprising rehmannia glutinosa is selected from the group consisting of: tablet, capsule, pill, injection, inhalant, buccal tablet, suppository, emulsion, microemulsion, submicron emulsion, nanoparticle, gel, powder, suspension emulsion, cream, jelly, spray, etc.

Preferably, the rehmannia root-containing composition can be administered by a mode selected from the group consisting of: oral administration, intestinal administration, subcutaneous injection, intramuscular injection, intravenous injection, nasal administration, transdermal administration, subconjunctival administration, intraocular administration, orbital administration, retrobulbar administration, retinal administration, choroidal administration, intrathecal injection, and the like.

The rehmannia root of the invention is rehmannia root powder or a rehmannia root extract.

Preferably, the rehmannia glutinosa libosch is a rehmannia glutinosa libosch extract.

In one embodiment of the invention, the ground-producing source is ground flour.

The invention also provides a preparation method of the rehmannia root powder, which comprises the following steps:

(1) cleaning and soaking radix rehmanniae;

(2) slicing;

(3) and (3) drying:

(4) and (4) crushing.

Preferably, the time for cleaning and soaking the dried rehmannia root in the step (1) is 10-30 min; more preferably, the soaking time is 20-25 min.

Preferably, the green land is cut into 1-2mm slices in the step (2).

Preferably, the drying mode in the step (3) is selected from drying in the sun, drying in the oven, drying at low temperature, vacuum drying or drying in the shade, so that the moisture of the raw ground surface is less than or equal to 0.5 percent.

Preferably, the land generation powder is obtained by crushing land generation to 100-1200 meshes. More preferably, the powder of the radix rehmanniae is obtained by crushing the radix rehmanniae to 800-1200 meshes.

Preferably, the method for extracting the rehmannia root extract is selected from the following steps: solvent extraction, percolation, decoction, reflux, continuous reflux, ultrasonic extraction, supercritical fluid extraction, steam distillation, sublimation, resin adsorption separation or gel chromatography.

More preferably, the extraction method is selected from solvent extraction, decoction or resin adsorption separation.

In one embodiment of the invention, the rehmannia glutinosa is a rehmannia glutinosa extract.

The invention also provides a preparation method of the radix rehmanniae extract, which comprises the following steps:

(1) drying and crushing the raw rehmannia root raw material to obtain rehmannia root coarse powder;

(2) extracting radix rehmanniae coarse powder with solvent, filtering, and concentrating under reduced pressure to obtain concentrated solution;

(3) passing the concentrated solution through an adsorption column, and eluting with water and ethanol to obtain an eluent;

(4) concentrating the eluate under reduced pressure, decolorizing, refining, concentrating under reduced pressure to obtain extract, and drying to obtain radix rehmanniae extract.

Preferably, the baking temperature in the step (1) is 80-110 ℃.

Preferably, the raw rehmannia root material in the step (1) is crushed into 10-100 meshes.

Preferably, the solvent in step (2) is selected from N, N-dimethylformamide, acetic acid, dichloromethane, methanol, ethanol, isopropanol, tert-butanol, acetonitrile or acetone. More preferably, the solvent is a 45% to 90% ethanol solution.

Preferably, the adsorption column filler in the step (3) is selected from one or more of HPD series, ADS series, HZ series, XAD series and D series macroporous resin fillers. More preferably, the adsorption column packing is selected from: one or a combination of more than one of HPD100, HZ18 and D101.

Preferably, the drying manner in the step (4) is selected from one or more of spray drying, vacuum drying, freeze drying, near infrared drying and microwave drying. More preferably, the drying is carried out in vacuum at a temperature of 30 to 50 ℃.

Drawings

Embodiments of the invention are described in detail below with reference to the attached drawing figures, wherein:

FIG. 1: a geodetically altered intestinal microbial species.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1 preparation of rehmannia root powder

Selecting and using rehmannia root with higher medicinal value for preparation, pouring the collected rehmannia root into cold water for soaking for 25min, cleaning, cutting the rehmannia root into slices with the thickness of 2mm, and placing the slices into a low-temperature drying box for drying, wherein the temperature range is as follows: 30-40 ℃, humidity range: 10-20% RH to make the surface moisture less than or equal to 0.5%, immediately inputting the dried radix rehmanniae into a pulverizer to pulverize in time when the dried radix rehmanniae is hot, pulverizing to 600 meshes, sterilizing the radix rehmanniae powder pulverized into powder, and vacuum packaging.

Example 2 ethanol extraction method for preparing a rehmannia root extract

Drying radix rehmanniae with high medicinal value, baking at 80 deg.C, pulverizing to 50 mesh to obtain radix rehmanniae coarse powder, extracting with 80% ethanol solution for 4 times, filtering the extractive solution, concentrating under reduced pressure to obtain radix rehmanniae concentrated solution, eluting with adsorption column filled with HPD100, washing with purified water, removing impurities, eluting with 60%, 70%, and 80% ethanol to obtain eluate, concentrating under reduced pressure, decolorizing, refining, concentrating under reduced pressure to obtain extract, and freeze drying to obtain radix rehmanniae extract.

Example 3 Water decoction method of radix rehmanniae extract

Extracting radix rehmanniae with high medicinal value, weighing 100g radix rehmanniae, placing in a decocting vessel with suitable volume, adding about 600mL water, soaking the medicinal materials for 1h, boiling, and heating for 0.5 h. Separating the decoction, decocting the residues for the second time, mixing the decoction with the first decoction, measuring the volume with a measuring cylinder, further boiling and concentrating the decoction to about 600mL if the volume exceeds 600mL, vacuum packaging the decoction after the corresponding volume is reached, putting into 7-8 small bags, and storing at 4 ℃ for later use.

Example 4 Effect of rehmannia root on intestinal microorganisms

The experimental monkey is taken as an experimental object in the experiment, the experimental medicine is the radix rehmanniae extract prepared according to the example 3, the administration mode is transnasal gavage administration, and the gavage is once a day for 14 continuous days. Collecting feces every day in 14 days after and 1 day before and after intragastric administration. The experimental criteria are as follows: the method comprises the steps of carrying out monkey feeding according to non-primate experimental animal feeding standards, flushing the bottom of an animal cage by 8 points every morning, placing a stainless steel mesh at the bottom of the animal cage, waiting for the monkey to defecate automatically, checking monkey ID after defecating, taking a picture of excrement, collecting the excrement by using an excrement collection pipe, paying attention to the excrement which is kept away from a mesh surface in the collection process, and then placing the collected excrement in a refrigerator at-80 ℃ for storage.

The DNA is extracted by using a strong fecal DNA extraction Kit (Qiagen, USA), 100ng of DNA is extracted from each sample, a 300-400bp DNA fragment is prepared by using a non-contact ultrasonicator, a high-throughput sequencing platform Library is used for constructing a directional optimization Kit VAHTS Nano DNA Library Prep Kit for Illumina (Vazyme, China) for sequencing, the sequencing depth reaches 3-5 million of samples, quality control is carried out on each sequencing reading, a non-human sequence is analyzed by using Kraken and Bracken, a user-defined database is used as reference, and the database comprises genomes of all bacteria, archaea, viruses, fungi and protozoa in RefSeq 12-22 days before 2017.

The results are shown in fig. 1 and table 1, and it is found that the effect of the extract of rehmannia glutinosa on intestinal microorganisms includes selectively increasing the amount of some bacteria, protozoa and archaea in the intestinal tract, and simultaneously inhibiting the amount of other bacteria in the intestinal tract and inhibiting some viruses in the intestinal tract.

TABLE 1 altered species of gut microorganisms

The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.

It should be noted that the various technical features described in the above embodiments can be combined in any suitable manner without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition.

Claims

1. Use of rehmanniae radix for regulating intestinal microorganisms.

2. The use of the rehmannia glutinosa libosch for modulating gut microbes according to claim 1, wherein the gut microbes are selected from one or a combination of two or more of bacteria, archaea, prokaryotes or viruses.

3. Use of the habitat according to claim 2 for modulating gut microbes by selectively increasing the number of bacteria in the gut selected from one or a combination of two or more of the genera Lactobacillus (Lactobacillus), Bacteroides (Bacteroides), Streptococcus (Streptococcus), dietotherlla (victivvallalles), Ruminococcus (Ruminococcus), flavobacterium (Flavonifractor), dithiabacter (Oscillibacter), clostridium (clostridium), enterococcus (intestinomonas), Fretibacterium, clostridium, adlereuthia or ethanologens (ethanologens).

4. Use of the dried rehmannia root for modulating gut microbes according to claim 2, wherein said modulating gut microbes is a selective inhibition of the number of gut microbes selected from one or a combination of two or more of Prevotella (Prevotella), Escherichia (Escherichia), Porphyromonas (Porphyromonas), helicobacter (Campylobacter), Vibrio butyricum (Anterostipes), Bacteroides (Bacteroides), Lactobacillus (Lactobacillus), Shigella (Shigella), Treponema (Treponema) or Eubacterium (Eubacterium).

5. The use of the dried rehmannia root according to claim 2, for modulating gut microbes, wherein the gut microbes are selected to inhibit the amount of viruses in gut, and the viruses are Staphylococcus phage (Staphylococcus phase).

6. The use of rehmannia glutinosa according to claim 2, for modulating gut microbiome selected from the group consisting of methanobrevibacterium (methanobacter) and methanococcus (methanophaera) to selectively increase the number of archaea in the gut.

7. The use of rehmannia glutinosa for modulating gut microbiome according to claim 2, wherein said modulating gut microbiome is a selective increase in the number of gut protozoa, said protozoa being blastocysts (B/astocystis).

8. The application of the radix rehmanniae in preparing the medicine is characterized in that the medicine is used for treating diseases related to intestinal flora disorder.

9. Use of a composition comprising rehmannia glutinosa for modulating gut microbiota.

10. The use of the composition comprising radix rehmanniae for regulating intestinal microorganisms according to claim 9, wherein the composition comprising radix rehmanniae is a combination of radix rehmanniae and one or more selected from qi tonics, blood tonics, yin tonics, cold phlegm-warming and resolving herbs, blood-cooling hemostatics, blood stasis removing hemostatics, edema-alleviating diuretics, heat-clearing and blood-cooling drugs or intestinal bacteria.

11. Use of a composition comprising rehmannia root for modulating gut microbiota according to claim 10, wherein the qi tonics are selected from the group consisting of: one or more of radix Ginseng, radix Panacis Quinquefolii, radix Codonopsis, radix Pseudostellariae, radix astragali, rhizoma Atractylodis Macrocephalae, rhizoma Dioscoreae, semen lablab album, radix Glycyrrhizae, fructus Jujubae, radix Et caulis Acanthopanacis Senticosi, gynostemma pentaphyllum, radix Rhodiolae, fructus Hippophae, maltose, and Mel; the blood-tonifying agent is selected from: one or more of radix Angelicae sinensis, radix Paeoniae alba, colla Corii Asini, Polygoni Multiflori radix, arillus longan or fructus Broussonetiae; the yin-tonifying medicine is selected from: radix Glehniae, radix Adenophorae, Bulbus Lilii, radix Ophiopogonis, radix asparagi, herba Dendrobii, rhizoma Polygonati Odorati, rhizoma Polygonati, radix Changii, fructus Lycii, Ecliptae herba, fructus Ligustri Lucidi, Mori fructus, semen Sesami Niger, carapax et Plastrum Testudinis, carapax Trionycis, Tremella, nidus Collocaliae or fish glue; the cold-phlegm warming and resolving medicine is selected from: one or more of rhizoma Pinelliae, rhizoma arisaematis, semen Sinapis Albae, fructus Gleditsiae Abnormalis, Inulae flos, Bulbus Fritillariae Cirrhosae, fructus Trichosanthis, caulis Bambusae in Taenia, succus Bambusae, concretio silicea Bambusae seu Schizostachyi, radix Peucedani, radix Platycodi or semen Scaphii Lychnophori; the blood-cooling hemostatics are selected from: one or more of herba Cephalanoploris, herba seu radix Cirsii Japonici, radix Sangusorbae, flos Sophorae Immaturus, folium Platycladi, lalang grass rhizome, radix Curcumae and radix Boehmeriae; the stasis-removing hemostatics are selected from: one or more of Notoginseng radix, radix Rubiae, pollen Typhae, Ophicalcitum, lignum Dalbergiae Odoriferae and crinis Carbonisatus; the diuresis-inducing and edema-alleviating drug is selected from: poria, Coicis semen, Polyporus, Alismatis rhizoma, exocarpium Benincase, stigma Maydis, bottle gourd, cortex Periplocae Radicis, semen Hoveniae, herba Euphorbiae Helioscopiae, Gryllotalpa or herba Capsellae; the heat-clearing and blood-cooling medicine is selected from: charred radix Et rhizoma Rhei, radix scrophulariae, cortex moutan, radix Paeoniae Rubra, radix Arnebiae, cornu Bubali, or herba Rabdosiae Lophanthoidis; the enteric bacteria are selected from one or more of Lactobacillus (Lactobacillus), Bacteroides (Bacteroides), Streptococcus (Streptococcus), food Valeriella (Victivallales), Ruminococcus (Ruminococcus), Flavobacterium (FlavoninFremonorus), Oscillatoria (Oscilobacter), Clostridium (Clostridium), Enteromomonas (Intestimonas), Fritibacter, Clinaciae, Adlercutzia, ethanologen (Ethanoligenins), Methanobacter (Methanobacter), Methanococcus (Methanophaga) or Blastocystis (Blastocystis).

12. Use of a composition comprising rehmannia glutinosa libosch for the manufacture of a medicament for the treatment of a condition associated with a disturbed intestinal flora.

13. The use according to any one of claims 1 to 12, wherein the rehmannia glutinosa is rehmannia glutinosa powder or a rehmannia glutinosa extract.

14. The use as claimed in claim 13, wherein the ground powder is prepared by pulverizing ground to 100-1200 mesh.

15. The use as claimed in claim 13, wherein the rehmannia glutinosa extract is extracted by a method selected from the group consisting of: solvent extraction, percolation, decoction, reflux, continuous reflux, ultrasonic extraction, supercritical fluid extraction, steam distillation, sublimation, resin adsorption separation or gel chromatography.