CN111658694A - Application of radix paeoniae alba in regulating intestinal microorganisms - Google Patents

Application of radix paeoniae alba in regulating intestinal microorganisms Download PDF

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CN111658694A
CN111658694A CN201910176481.4A CN201910176481A CN111658694A CN 111658694 A CN111658694 A CN 111658694A CN 201910176481 A CN201910176481 A CN 201910176481A CN 111658694 A CN111658694 A CN 111658694A
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radix
gut
peony root
white peony
lactobacillus
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魏来
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Zhuhai Qiwei Bio Technology Ltd
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Zhuhai Qiwei Bio Technology Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/71Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/65Paeoniaceae (Peony family), e.g. Chinese peony
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • A61P33/02Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis

Abstract

The invention provides application of radix paeoniae alba in regulating intestinal microorganisms and application of radix paeoniae alba in preparing a medicine, wherein the medicine is used for treating diseases related to intestinal microorganism disorders.

Description

Application of radix paeoniae alba in regulating intestinal microorganisms
Technical Field
The invention relates to the field of medicine and health care, in particular to application of white paeony root and a composition containing the white paeony root 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.
White peony root (Cynanchum otophyllum) is bitter and sour in taste, slightly cold in nature, enters liver and spleen channels, has good effects of calming liver, relieving pain, nourishing blood, regulating menstruation, astringing yin and arresting sweating, and is one of the most commonly used traditional Chinese medicines. The white peony root mainly contains glycosides, terpenes, flavonoids and tannins, and also contains 32 components of white peony root basic oil, resin, sugar, protein, metal elements of Mn, Fe, Cu, Cd, Ph and 17 amino acids, and has pharmacological effects of resisting inflammation, resisting bacteria, protecting liver and relieving pain.
In the prior art, the process of regulating intestinal microorganisms of white paeony root has a certain progress, such as: non-patent literature "observe the clinical efficacy of angelica and peony powder for treating liver cirrhosis by adding flavor based on intestinal microorganism regulation of" intestine-liver axis "(Liu Gift sword, etc., world Chinese medicine, 2017, 12(8):1789-1792.) reveals that: the main action mechanism of the angelica and peony powder for treating liver cirrhosis is probably related to improving intestinal microbial disorder, repairing intestinal mucosal barrier, relieving endotoxemia and the like. Patent document CN108815364A discloses a probiotic fermented traditional Chinese medicine preparation for treating constipation of pigs and a preparation method thereof, wherein the traditional Chinese medicine preparation contains radix paeoniae alba, and the method comprises the steps of crushing the traditional Chinese medicine preparation, adding EM bacteria, and mixing the traditional Chinese medicine preparation with a breathing bag for fermentation. The traditional Chinese medicine preparation can effectively cure the constipation of pigs and restore the ecological balance of intestinal microorganisms of the pigs. Patent document CN107050415A discloses a pharmaceutical capsule for preventing and treating chronic diarrhea, said pharmaceutical capsule comprises white peony root extract, and said pharmaceutical capsule can significantly reduce the development of chronic diarrhea, and has the functions of improving the internal environment of intestinal tract, promoting the repair and regeneration of intestinal mucosa, and protecting against the invasion of harmful microorganisms. However, the specific strains regulated by white peony root are not disclosed in the prior art, and in order to make up for the defect, the inventor of the present invention has made relevant researches on the specific strains in the white peony root for regulating intestinal tract.
Disclosure of Invention
The inventor researches and discovers that the white paeony root can obviously improve the quantity of beneficial bacteria in intestinal tracts, inhibit the quantity of harmful bacteria and regulate intestinal microorganisms.
Accordingly, it is an object of the present invention to provide the use of white peony or a composition comprising white peony for the regulation of gut microbiology. It is a further object of the present invention to provide the use of white peony root or a composition comprising white peony root in the manufacture of a medicament for the treatment of a disease associated with an intestinal disorder.
In a first aspect of the invention, the use of white peony root for regulating intestinal microorganisms is provided.
Preferably, the white paeony root mainly contains glycosides, terpenes, flavonoids and tannins, and also contains 32 components of white paeony root basic oil, resin, sugar, protein, metal elements of Mn, Fe, Cu, Cd, Ph and 17 amino acids. Wherein the main effective component of radix Paeoniae alba is Total Glucosides of Paeonia (TGP), and contains paeoniflorin (above 90%), hydroxy paeoniflorin, albiflorin, and benzoylpaeony.
Preferably, the intestinal microorganisms are selected from one or a combination of more than two of bacteria, archaea, protozoa or viruses.
Preferably, the intestinal microorganisms are regulated to selectively increase the number of bacteria in the intestine, the bacteria being selected from one or a combination of two or more of the genera Lactobacillus (Lactobacillus), Ruminococcus (Ruminococcus), Streptococcus (Streptococcus), food millet (victivlales), Eubacterium (Eubacterium), Bifidobacterium (Bifidobacterium), Coprococcus (coprococus), olsenia (Olsenella), kiritiella or Clostridium (Clostridium).
More preferably, the intestinal microorganisms are selected to selectively increase the number of bacteria in the intestine, wherein the bacteria are selected from one or a combination of two or more of the genera rumen (Ruminococcus), Streptococcus (Streptococcus), food millet (victivlales), Eubacterium (Eubacterium), Bifidobacterium (Bifidobacterium), Coprococcus (Coprococcus), continental osmia (Olsenella), kiritiella or Clostridium (Clostridium).
In a specific embodiment of the invention, the modulating gut microorganism is selected from the group consisting of Lactobacillus agilis, Lactobacillus murinus, Lactobacillus johnsonii, Ruminococcus championelensis, Lactobacillus mucosae, Streptococcus infantaris, Streptococcus agrostis, Staphylococcus aureus, Victivalla bacterium CCUG 44730, Eubacterium siaeum, Bifidobacterium adolescentesis, Streptococcus luteosis, Coprococcus sp.55/1, Streptococcus equinus, Mycobacterium alcanum, Streptococcus alidium, Streptococcus faecalis, Lactobacillus strain-P2300, or a combination of two or more thereof.
Preferably, the intestinal microorganisms are regulated to selectively inhibit the amount of bacteria in the intestinal tract, wherein the bacteria are selected from one or more of the genera Aminococcus (Acidaminococcus), Prevotella (Prevotella), helicobacter (Campylobacter), Macrosphaera (Megasphaera), Lactobacillus (Lactobacilli), Bacteroides (Bacteroides) or Enterococcus (Enterococcus).
More preferably, the intestinal microorganisms are regulated to selectively inhibit the amount of bacteria in the intestinal tract, wherein the bacteria are selected from one or more of the genera Aminococcus (Acidaminococcus), Prevotella (Prevotella), helicobacter (Camptobacter), Macrosphaera (Megasphaera), Bacteroides (Bacteroides) or Enterococcus (Enterococcus).
In one embodiment of the invention, the modulating of the gut microbes to selectively inhibit the amount of bacteria in the gut is selected from the group consisting of Acidonococcus ferments, Prevotella copri, Campylobacter jejuni, Helicobacter cinaedi, uncultred bacteria sp, Megasphaera elsdenii, Prevotella sp.RS2, Lactobacillus salivarius, and Enterococushirae.
Preferably, the regulation of the gut microbiome is a selective increase in the number of viruses in the gut, said viruses being human fecal viruses.
In one embodiment of the present invention, the regulation of the intestinal microorganisms is a selective increase in the amount of a virus in the intestine, and the virus is Human diseases pecoviruses.
Preferably, said modulating gut microbiome is a selective inhibition of the amount of a virus in the gut, said virus being selected from Enterococcus faecalis phages (Enterococcus) and/or streptococcal viruses (Streptococcus virus).
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 selected from Enterococcus phage vB EfaP IME195 and/or streptococcus virus C1.
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).
In one embodiment of the present invention, the modulating of the gut microbes is a selective increase of the number of archaea in the gut, wherein the archaea is selected from one or a combination of two or more of methanobacteriobacter sp.ye315, methanobacteriosmithii, methanobacteriobacter millerae, or methanophaera stadtmanae.
Preferably, the intestinal microorganism is regulated to selectively increase the number of protozoa in the intestinal tract, such as blastocysts (blastocysts).
In one embodiment of the invention, said modulating gut microbiome is a selective increase in the number of protozoa in the gut, said protozoa being blastocysts sp.
In a second aspect of the invention, there is provided use of white peony root in the manufacture of a medicament for the treatment of a disease associated with a disturbed intestinal flora.
Preferably, the white paeony root mainly contains glycosides, terpenes, flavonoids and tannins, and also contains 32 components of white paeony root basic oil, resin, sugar, protein, metal elements of Mn, Fe, Cu, Cd, Ph and 17 amino acids. Wherein the main effective component of radix Paeoniae alba is Total Glucosides of Paeonia (TGP), and contains paeoniflorin (above 90%), hydroxy paeoniflorin, albiflorin, and benzoylpaeony.
Preferably, the intestinal flora is selected from one or a combination of more than two of bacteria, archaea, protozoa 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 a use of a composition comprising white peony root for regulating gut microbiota.
Preferably, the white paeony root mainly contains glycosides, terpenes, flavonoids and tannins, and also contains 32 components of white paeony root basic oil, resin, sugar, protein, metal elements of Mn, Fe, Cu, Cd, Ph and 17 amino acids. Wherein the main effective component of radix Paeoniae alba is Total Glucosides of Paeonia (TGP), and contains paeoniflorin (above 90%), hydroxy paeoniflorin, albiflorin, and benzoylpaeony.
Preferably, the intestinal microorganisms are selected from one or a combination of more than two of bacteria, archaea, protozoa or viruses.
Preferably, the intestinal microorganism is regulated to selectively increase the number of bacteria in the intestinal tract, wherein the bacteria are selected from one or a combination of two or more of Lactobacillus (Lactobacillus), Ruminococcus (Ruminococcus), Streptococcus (Streptococcus), food millet (victivlales), Eubacterium (Eubacterium), Bifidobacterium (Bifidobacterium), Coprococcus (coprococus), olsenia (Olsenella), kiritiella or Clostridium (Clostridium).
More preferably, the intestinal microorganisms are selected to selectively increase the number of bacteria in the intestine, wherein the bacteria are selected from one or a combination of two or more of the genera rumen (Ruminococcus), Streptococcus (Streptococcus), food millet (victivlales), Eubacterium (Eubacterium), Bifidobacterium (Bifidobacterium), Coprococcus (Coprococcus), continental Eubacterium (Olsenella), kiritiella or Clostridium (Clostridium).
In a specific embodiment of the invention, the modulating gut microorganism is selected from the group consisting of Lactobacillus agilis, Lactobacillus murinus, Lactobacillus johnsonii, Ruminococcus championelensis, Lactobacillus mucosae, Streptococcus infantaris, Streptococcus agrostis, Staphylococcus aureus, Victivalla bacterium CCUG 44730, Eubacterium siaeum, Bifidobacterium adolescentesis, Streptococcus luteosis, Coprococcus sp.55/1, Streptococcus equinus, Mycobacterium alcanum, Streptococcus alidium, Streptococcus faecalis, Lactobacillus strain-P2300, or a combination of two or more thereof.
Preferably, the intestinal microorganisms are regulated to selectively inhibit the amount of bacteria in the intestinal tract, wherein the bacteria are selected from one or more of the genera Aminococcus (Acidaminococcus), Prevotella (Prevotella), helicobacter (Campylobacter), Macrosphaera (Megasphaera), Lactobacillus (Lactobacilli), Bacteroides (Bacteroides) or Enterococcus (Enterococcus).
More preferably, the intestinal microorganisms are regulated to selectively inhibit the amount of bacteria in the intestinal tract, wherein the bacteria are selected from one or more of the genera Aminococcus (Acidaminococcus), Prevotella (Prevotella), helicobacter (Camptobacter), Macrosphaera (Megasphaera), Bacteroides (Bacteroides) or Enterococcus (Enterococcus).
In one embodiment of the invention, the modulating of the gut microbes to selectively inhibit the amount of bacteria in the gut is selected from the group consisting of Acidonococcus ferments, Prevotella copri, Campylobacter jejuni, Helicobacter cinaedi, uncultred bacteria sp, Megasphaera elsdenii, Prevotella sp.RS2, Lactobacillus salivarius, and Enterococushirae.
Preferably, the regulation of the gut microbiome is a selective increase in the number of viruses in the gut, said viruses being human fecal viruses.
In one embodiment of the present invention, the regulation of the intestinal microorganisms is a selective increase in the amount of a virus in the intestine, and the virus is Human diseases pecoviruses.
Preferably, said modulating gut microbiome is a selective inhibition of the amount of a virus in the gut, said virus being selected from Enterococcus faecalis phages (Enterococcus) and/or streptococcal viruses (Streptococcus virus).
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 selected from Enterococcus phage vB EfaP IME195 and/or streptococcus virus C1.
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).
In one embodiment of the present invention, the modulating of the gut microbes is a selective increase of the number of archaea in the gut, wherein the archaea is selected from one or a combination of two or more of methanobacteriobacter sp.ye315, methanobacteriosmithii, methanobacteriobacter millerae, or methanophaera stadtmanae.
Preferably, the intestinal microorganism is regulated to selectively increase the number of protozoa in the intestinal tract, such as blastocysts (blastocysts).
In one embodiment of the invention, said modulating gut microbiome is a selective increase in the number of protozoa in the gut, said protozoa being blastocysts sp.
Preferably, the composition containing the white paeony root is the combination of the white paeony root 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-inducing and swelling-reducing 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 rehmanniae Preparata, 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: one or more of radix rehmanniae, charred radix Et rhizoma Rhei, radix scrophulariae, cortex moutan, radix Paeoniae Rubra, radix Arnebiae, cornu Bubali, and herba Rabdosiae Lophanthoidis; the enteric bacteria are selected from one or more of Lactobacillus (Lactobacillus), Ruminococcus (Ruminococcus), Streptococcus (Streptococcus), food millet (Victivallales), Eubacterium (Eubacterium), Bifidobacterium (Bifidobacterium), Coprococcus (Coprococcus), Erysipelothrix (Olsenerla), Kiritimatinib, Clostridium (Clostridium), Methanobacterium (Methanobacter), Methanococcus (Methanosphaera) 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.
Further preferably, the enteric bacteria are selected from the group consisting of Lactobacillus agilis, Lactobacillus murinus, Lactobacillus johnsonii, Saccharomyces champanensis, Lactobacillus mucosae, Streptococcus infantarius, Streptococcus faecalis, Lactobacillus gasololyticus, Victivallisbacter CCUG 44730, Eubacterium siaeum, Bifidobacterium adolescenosis, Streptococcus lutescens, Coprococcus sp.ART55/1, Streptococcus equus, Mycobacterium alcula, Streptococcus aureus, Streptococcus pyogenes, Bifidobacterium octopus, Bacillus oxysporum, Bacillus sp.sp.sp.sp.sp.sp.sp.sp.sp.sp.sp.sp.sp.2300, Lactobacillus acidophilus, Bacillus subtilis, Bacillus mucilaginosus, Bacillus subtilis, or combinations of two or more.
In a fourth aspect of the invention, there is provided use of a composition comprising white peony root in the manufacture of a medicament for the treatment of a condition associated with a disturbed intestinal flora.
Preferably, the white paeony root mainly contains glycosides, terpenes, flavonoids and tannins, and also contains 32 components of white paeony root basic oil, resin, sugar, protein, metal elements of Mn, Fe, Cu, Cd, Ph and 17 amino acids. Wherein the main effective component of radix Paeoniae alba is Total Glucosides of Paeonia (TGP), and contains paeoniflorin (above 90%), hydroxy paeoniflorin, albiflorin, and benzoylpaeony.
Preferably, the composition containing the white paeony root is the combination of the white paeony root 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-inducing and swelling-reducing 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 rehmanniae Preparata, 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: one or more of radix rehmanniae, charred radix Et rhizoma Rhei, radix scrophulariae, cortex moutan, radix Paeoniae Rubra, radix Arnebiae, cornu Bubali, and herba Rabdosiae Lophanthoidis; the enteric bacteria are selected from one or more of Lactobacillus (Lactobacillus), Ruminococcus (Ruminococcus), Streptococcus (Streptococcus), food millet (Victivallales), Eubacterium (Eubacterium), Bifidobacterium (Bifidobacterium), Coprococcus (Coprococcus), Erysipelothrix (Olsenerla), Kiritimatinib, Clostridium (Clostridium), Methanobacterium (Methanobacter), Methanococcus (Methanosphaera) 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.
Further preferably, the enteric bacteria are selected from the group consisting of Lactobacillus agilis, Lactobacillus murinus, Lactobacillus johnsonii, Saccharomyces champanensis, Lactobacillus mucosae, Streptococcus infantarius, Streptococcus faecalis, Lactobacillus gasololyticus, Victivallisbacter CCUG 44730, Eubacterium siaeum, Bifidobacterium adolescenosis, Streptococcus lutescens, Coprococcus sp.ART55/1, Streptococcus equus, Mycobacterium alcula, Streptococcus aureus, Streptococcus pyogenes, Bifidobacterium octopus, Bacillus oxysporum, Bacillus sp.sp.sp.sp.sp.sp.sp.sp.sp.sp.sp.sp.sp.2300, Lactobacillus acidophilus, Bacillus subtilis, Bacillus mucilaginosus, Bacillus subtilis, or combinations of two or more.
Preferably, the intestinal flora is selected from one or a combination of more than two of bacteria, archaea, protozoa 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.
According to the composition containing the white paeony root, the part ratio of the white paeony root 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 edema relieving medicines, heat clearing and blood cooling medicines or intestinal bacteria is 1-99: 99-1.
Preferably, the composition containing white peony root further comprises pharmaceutically acceptable auxiliary materials, wherein the auxiliary materials are selected from: carrier, diluent, adhesive, lubricant and wetting agent.
Preferably, the dosage form of the composition comprising white peony root is selected from: tablet, capsule, pill, injection, inhalant, buccal tablet, suppository, emulsion, microemulsion, submicron emulsion, nanoparticle, gel, powder, suspension emulsion, cream, jelly, spray, etc.
Preferably, the composition comprising white peony root can be administered in a manner 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 white paeony root is white paeony root powder or a white paeony root extract.
Preferably, the white paeony root is white paeony root extract.
In one embodiment of the invention, the white paeony root powder is prepared from dry roots harvested in summer and autumn.
The invention also provides a preparation method of the white paeony root powder, which comprises the following steps:
(1) digging dry roots of the white paeony roots in summer and autumn;
(2) washing the dried roots in the step (1) to remove heads, tails and fine roots;
(3) removing outer skin, and decocting in boiling water; or boiling in boiling water and removing outer skin;
(4) slicing, drying and crushing to obtain white paeony root powder.
Preferably, the slicing in the step (4) is to slice the white peony root into slices of 1-2 mm.
Preferably, the drying mode of the white paeony root in the step (4) is selected from drying in the sun, drying in the oven, drying in the shade and drying at low temperature, so that the moisture on the surface of the white paeony root is less than or equal to 0.5 percent.
Preferably, the white paeony root powder is prepared by crushing white paeony root into 30-1200 meshes.
Preferably, the white paeony root powder is prepared by grinding white paeony root to 80-800 meshes.
In one embodiment of the invention, the radix paeoniae alba powder is prepared by crushing the radix paeoniae alba into 150-500 meshes.
In one embodiment of the present invention, the white peony root extract is an extract of dry roots of white peony harvested in summer and autumn.
Preferably, the extraction method of the white peony 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.
Further preferably, the extraction method is selected from: solvent extraction method, and decocting method.
The invention provides a preparation method of a white paeony root extract, which comprises the following steps:
(1) pulverizing radix Paeoniae alba into coarse powder;
(2) adding a solvent for extraction;
(3) heating and refluxing, and collecting the extracting solution;
(4) decompressing the extract collected in the step (3) to recover ethanol;
(5) dissolving with appropriate amount of water, passing through adsorption column, eluting with water and ethanol, and collecting ethanol;
(6) concentrating under reduced pressure to obtain soft extract, and drying to obtain radix Paeoniae alba extract.
Preferably, the coarse powder in the step (1) is prepared by crushing the white paeony root into 10-100 meshes.
Preferably, the solvent in the step (2) is 25% -95% ethanol water solution;
preferably, the volume amount of the solvent added in the step (2) is 2-18 times of that of the white paeony root medicinal material.
Preferably, the heating reflux in the step (3) is carried out for 1 to 8 times, and each time lasts for 0.5 to 2.5 hours.
Preferably, the ethanol elution in the step (5) is 15%, 25% and 35% ethanol water solution gradient elution until the reaction of the glycoside is negative.
Preferably, the adsorption column packing in step (5) is selected from: one or more of HPD series, ADS series, HZ series, XAD series and D series macroporous resin fillers. Further 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 (6) is selected from: spray drying, vacuum drying, freeze drying, near infrared drying and microwave drying. Further preferably vacuum drying at 30-50 deg.C
Drawings
Embodiments of the invention are described in detail below with reference to the attached drawing figures, wherein:
FIG. 1: white peony root 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 white peony root powder
Selecting dry radix paeoniae alba roots with high medicinal value for preparation, cleaning the dug dry roots in cold water, removing head, tail, fine roots and outer skins, boiling in boiling water for 10min, cutting into slices of 1.5mm, putting into a low-temperature drying oven for drying at the drying temperature of 30-40 ℃ and the humidity of 10-20% RH until the surface moisture of the radix paeoniae alba slices is less than or equal to 0.5%, and then conveying the dried radix paeoniae alba slices into a pulverizer while the slices are hot to pulverize, and pulverizing to 500 meshes to obtain the radix paeoniae alba powder.
Example 2 preparation of white peony root extract by ethanol extraction
Selecting dry white paeony roots with high medicinal value for extraction, crushing the dry white paeony roots into coarse powder of 30 meshes, extracting 5 times by using 85 percent ethanol water solution with the volume 10 times that of the dry white paeony roots, heating and refluxing for 3 times, each time for 2 hours, collecting extract, recovering ethanol under reduced pressure, adding a proper amount of water for dissolving, then passing through an adsorption column with a filler D101, washing by using purified water, removing impurities, performing gradient elution by using 15 percent, 25 percent and 35 percent ethanol water solution until the reaction of glycoside is negative, performing reduced pressure concentration on obtained eluent, decoloring, refining into extract, and performing vacuum drying to obtain the white paeony root extract.
EXAMPLE 3 preparation of white peony root extract by Water decoction
Selecting radix Paeoniae alba dry root with high medicinal value for extraction, weighing 100g radix Paeoniae alba dry root, placing in a decocting vessel with suitable volume, adding about 600mL water, immersing 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 white peony on gut microbiology
The experimental monkey is taken as an experimental object in the experiment, the experimental medicine is the white paeony root extract prepared according to the embodiment 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 statistics on the results show that the effect of the paeonia lactiflora pall extract on intestinal microorganisms includes selectively increasing the number of bacteria, protozoa and archaea in the intestinal tract, and simultaneously inhibiting the number of other bacteria in the intestinal tract and inhibiting viruses in the intestinal tract.
TABLE 1 altered species of gut microbes from Paeonia lactiflora
Figure BDA0001989780100000151
Figure BDA0001989780100000161
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 (16)

1. Use of radix Paeoniae alba in regulating intestinal microorganisms is provided.
2. The use of radix paeoniae alba for modulating gut microbes as claimed in claim 1 wherein the gut microbes are selected from one or a combination of two or more of bacteria, archaea, protozoa or viruses.
3. The use of white peony root according to claim 2, for modulating gut microbiome selected from the group consisting of Lactobacillus (Lactobacillus), Ruminococcus (Ruminococcus), Streptococcus (Streptococcus), food millet (victivlales), Eubacterium (Eubacterium), Bifidobacterium (Bifidobacterium), Coprococcus (Coprococcus), Olsenella (Olsenella), kiritiella, or Clostridium (Clostridium), to selectively increase the number of gut microbiome.
4. The use of white peony root according to claim 2, wherein said modulating gut microbes is selected from the group consisting of one or a combination of two or more of the amino acid coccus (Acidaminococcus), Prevotella (Prevotella), helicobacter (Campylobacter), Megasphaera (Megasphaera), Lactobacillus (Lactobacillus), Bacteroides (Bacteroides) or Enterococcus (Enterococcus), for selectively inhibiting the amount of said bacteria in the gut.
5. The use of radix paeoniae alba for modulating gut microbiology according to claim 2, wherein said modulating gut microbiology is a selective increase in the number of viruses in the gut, said viruses being human fecal viruses.
6. The use of radix Paeoniae alba for modulating gut microbiology according to claim 2, wherein said modulating gut microbiology is a selective inhibition of the amount of a virus in the gut selected from Enterococcus faecalis phage (Enterococcus) and/or streptococcal virus (Streptococcus virus).
7. The use of white peony root according to claim 2, for modulating gut microbiome selected from the group consisting of methanobrevibacterium (methanobacter) and/or methanococcus (methanophagera) in the gut to selectively increase the number of archaea in the gut.
8. The use of white peony root according to claim 2, for modulating gut microbiome, wherein said modulating gut microbiome is a selective increase in the number of gut protozoa, said protozoa being blastocysts (blastocysts).
9. The application of the white peony root in preparing the medicine is characterized in that the medicine is used for treating diseases related to intestinal flora disorder.
10. Use of a composition comprising white peony root for modulating gut microbiology.
11. The use of the composition comprising white peony root according to claim 10, wherein the composition comprising white peony root is a combination of white peony root and one or more than two selected from qi tonics, blood tonics, yin tonics, cold phlegm-warming and resolving herbs, blood-cooling hemostatics, blood stasis removing hemostatics, edema reliever, heat-clearing and blood-cooling herbs or enteric bacteria.
12. Use of a composition comprising white peony root according to claim 11, wherein the said air-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 rehmanniae Preparata, 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: one or more of radix rehmanniae, charred radix Et rhizoma Rhei, radix scrophulariae, cortex moutan, radix Paeoniae Rubra, radix Arnebiae, cornu Bubali, and herba Rabdosiae Lophanthoidis; the enteric bacteria are selected from one or more of Lactobacillus (Lactobacillus), Ruminococcus (Ruminococcus), Streptococcus (Streptococcus), food millet (Victivallales), Eubacterium (Eubacterium), Bifidobacterium (Bifidobacterium), Coprococcus (Coprococcus), Erysipelothrix (Olsenerla), Kiritimatinib, Clostridium (Clostridium), Methanobacterium (Methanobacter), Methanococcus (Methanosphaera) or Blastocystis (Blastocystis).
13. Use of a composition comprising white peony root in the manufacture of a medicament for the treatment of a condition associated with a disturbed intestinal flora.
14. The use of any one of claims 1-13, wherein the white peony root is white peony root powder or white peony root extract.
15. The use of claim 14, wherein the white peony root powder is prepared by pulverizing white peony root to 30-1200 mesh.
16. The use of claim 14, wherein the white peony root 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.
CN201910176481.4A 2019-03-08 2019-03-08 Application of radix paeoniae alba in regulating intestinal microorganisms Pending CN111658694A (en)

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