Use of a traditional Chinese medicine composition in the preparation of a medicament for improving intestinal flora imbalance

Abstract

The present invention relates to the use of a traditional Chinese medicine composition in the preparation of a drug for improving intestinal flora imbalance. Compared with the prior art, the beneficial effects of the present invention include: it is found in this application that a traditional Chinese medicine composition can improve intestinal flora imbalance, and the application of this drug in intestinal flora imbalance increases the indications of the traditional Chinese medicine composition, providing a new drug option for the treatment of clinical patients with intestinal flora imbalance diseases.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly relates to a new use of a traditional Chinese medicine composition, and more particularly to an application of a traditional Chinese medicine composition in the preparation of a drug for improving intestinal flora imbalance. Background Art

[0002] The intestinal flora is closely related to multiple aspects of the host, such as digestion and absorption, nutrient metabolism, immune inflammation, etc., and plays a key role in the occurrence and development of diseases. Various studies on the intestinal flora have also received continuous attention in recent years. Changes in the composition of the intestinal flora, changes in bacterial metabolic activity, or changes in the local distribution of the flora can all cause flora disorders. And the disordered intestinal flora can further participate in the pathogenesis of inflammation, infection, allergic diseases, and cancer through the enterohepatic axis, the gut-brain axis, the gut-skin axis, etc. It can be said that "pulling one hair moves the whole body". Therefore, a stable and good intestinal flora environment is very important for the health and homeostasis of the body.

[0003] For the treatment of intestinal flora imbalance, there are currently various treatment methods, including probiotic preparations, fecal microbiota transplantation, traditional Chinese medicine treatment, etc. Probiotic preparations refer to active microbial preparations that can promote the balance of the intestinal flora and play a beneficial role in the host. Common probiotics include Lactobacillus, Bifidobacterium, Clostridium butyricum, yeast, Bacillus licheniformis, Bacillus subtilis, etc. A number of studies have confirmed that probiotic preparations can regulate the balance of the intestinal flora of patients and reduce the inflammatory response by reducing the expression of intestinal-related inflammatory receptors. However, there are also some deficiencies in the treatment of intestinal flora imbalance with probiotics. For example, some people will have adverse reactions such as abdominal distension, constipation, and migraine after taking probiotics. Fecal microbiota transplantation refers to transplanting the functional flora in the feces of healthy people into the gastrointestinal tract of patients to reconstruct the intestinal flora with normal functions, so as to treat intestinal flora imbalance. Fecal microbiota transplantation is often used to treat severe intestinal flora imbalance and intestinal and extra-intestinal diseases related to the intestinal flora. However, the exact efficacy of fecal microbiota transplantation for flora imbalance is still not very clear at present. Some patients can achieve clinical remission, while the flora imbalance problems of other patients have not been improved. In addition, issues such as the indications, administration methods, patient and donor screening, and patient pretreatment of fecal microbiota transplantation still need to be clarified. Therefore, there is an urgent need for more effective drugs to treat intestinal flora disorders.

[0004] The traditional Chinese medicine composition preparation Wushe Zhiyang Pills is included in the 1987 edition of the Guangdong Provincial Drug Standard and has the effects of nourishing blood and expelling wind, and resolving dampness and relieving itching. It is applicable to pruritic skin diseases such as skin pruritus, urticaria, and vulvar pruritus in women. There is no report on the application of this preparation in the preparation of drugs for improving intestinal flora imbalance. Summary of the Invention

[0005] Based on this, the purpose of the embodiments of the present application includes providing an application of a traditional Chinese medicine composition in the preparation of a drug for improving intestinal flora imbalance;

[0006] The active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by mass: 80-120 parts of Zaocys dhumnades, 1800-2200 parts of Cortex Moutan, 800-1200 parts of Cortex Phellodendri Chinensis, 8-12 parts of Calculus Bovis, 7800-8200 parts of Atractylodes lancea, 800-1200 parts of Saposhnikovia divaricata, 1800-2200 parts of Angelica sinensis, 0.8-1.2 parts of snake bile, 13000-18000 parts of Fructus Cnidii, 1800-2200 parts of Sophora flavescens, and 80-120 parts of Radix Ginseng Fibra.

[0007] In some embodiments of the present application, the active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by mass: 100 parts of Zaocys dhumnades, 2000 parts of Cortex Moutan, 1000 parts of Cortex Phellodendri Chinensis, 10 parts of Calculus Bovis, 8000 parts of Atractylodes lancea, 1000 parts of Saposhnikovia divaricata, 2000 parts of Angelica sinensis, 1 part of snake bile, 15000 parts of Fructus Cnidii, 2000 parts of Sophora flavescens, and 100 parts of Radix Ginseng Fibra.

[0008] In some embodiments of the present application, the dosage form of the drug is pill, granule, suppository, capsule, tablet, dripping pill, injection or powder.

[0009] In some embodiments of the present application, the intestinal flora dysbiosis includes a decrease in the relative abundance of the Bacteroidota phylum flora, and an increase in the relative abundances of the Campilobacterota phylum and Desulfobacterota phylum flora.

[0010] In some embodiments of the present application, the intestinal flora dysbiosis includes a decrease in the relative abundances of the Muribaculaceae family and Bacteroidaceae family flora.

[0011] In some embodiments of the present application, the intestinal flora dysbiosis includes a decrease in the relative abundance of the Bacteroides genus flora, and an increase in the relative abundances of the Lactobacillus genus and Odoribacter genus flora.

[0012] In some embodiments of the present application, the intestinal flora dysbiosis includes, but is not limited to, the intestinal flora dysbiosis caused by ulcerative colitis or / and constipation.

[0013] In some embodiments of the present application, the subjects of the drug are mammals.

[0014] In some embodiments of the present application, the mammal is a human.

[0015] In some embodiments of the present application, the mammal is a mouse.

[0016] In some embodiments of the present application, the mouse is a small mouse.

[0017] Compared with the prior art, the beneficial effects of the present application include:

[0018] The present application discovers that a traditional Chinese medicine composition can improve intestinal flora imbalance. The application of this drug in intestinal flora imbalance increases the indications of this traditional Chinese medicine composition and provides a new drug option for the treatment of clinical patients with intestinal flora imbalance diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the embodiments of the present application and more completely understand the present application and its beneficial effects, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the following drawings are only some embodiments of the present application. For those skilled in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0020] Figure 1 PCA analysis of the effect of Wushe Zhiyang Pills on the intestinal flora of mice;

[0021] Figure 2 Effect of Wushe Zhiyang Pills on the relative abundances of phyla of the intestinal flora of mice;

[0022] Figure 3 Effect of Wushe Zhiyang Pills on the relative abundances of the phyla Bacteroidota, Campilobacterota, and Desulfobacterota of the intestinal flora of mice;

[0023] Figure 4 Effect of Wushe Zhiyang Pills on the relative abundances of families of the intestinal flora of mice;

[0024] Figure 5 Effect of Wushe Zhiyang Pills on the relative abundances of the families Muribaculaceae and Bacteroidaceae of the intestinal flora of mice;

[0025] Figure 6 Effect of Wushe Zhiyang Pills on the relative abundances of genera of the intestinal flora of mice;

[0026] Figure 7 Effect of Wushe Zhiyang Pills on the relative abundances of the genera Bacteroides, Lactobacillus, and Odoribacter of the intestinal flora of mice. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0027] The present invention will be further described in detail below in conjunction with the accompanying drawings, embodiments and examples. It should be understood that these embodiments and examples are only used to illustrate the present invention and not to limit the scope of the present invention. The purpose of providing these embodiments and examples is to make the disclosure of the present invention more thoroughly and comprehensively understood. It should also be understood that the present invention can be implemented in many different forms and is not limited to the embodiments and examples described herein. Those skilled in the art can make various changes or modifications without departing from the connotation of the present invention, and the equivalent forms obtained also fall within the protection scope of this application. In addition, in the following description, a large number of specific details are given to provide a more thorough understanding of the present invention. It should be understood that the present invention can be implemented without one or more of these details.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which this invention belongs. The terms used in the description of the present invention herein are only for the purpose of describing the embodiments and examples and are not intended to limit the present invention.

[0029] Term

[0030] Unless otherwise stated or there is a contradiction, the terms or phrases used herein have the following meanings:

[0031] The selection scope of the terms "and / or", "or / and", "and / or" used herein includes any one of two or more related listed items, and also includes any and all combinations of the related listed items. The said any and all combinations include combinations of any two related listed items, any more related listed items, or all related listed items. It should be noted that when at least two conjunctions selected from "and / or", "or / and", "and / or" are used to connect at least three items, it should be understood that in this application, this technical solution undoubtedly includes the technical solution connected by "logical AND", and also undoubtedly includes the technical solution connected by "logical OR". For example, "A and / or B" includes three parallel solutions: A, B, and A + B. Another example is the technical solution of "A, and / or, B, and / or, C, and / or, D", which includes any one of A, B, C, D (that is, the technical solution connected by "logical OR"), and also includes any and all combinations of A, B, C, D, that is, it includes combinations of any two or any three of A, B, C, D, and also includes the combination of the four items A, B, C, D (that is, the technical solution connected by "logical AND").

[0032] All suitable combination ways of any two or any two or more items in the listed items are included in the "combination thereof", "any combination thereof", "any combination mode thereof", etc. used herein.

[0033] In this text, the "suitable" in "suitable combination method", "suitable method", "any suitable method", etc. is subject to being able to implement the technical solution of the present invention, solve the technical problems of the present invention, and achieve the expected technical effects of the present invention.

[0034] In this text, "preferred", "better", "more preferable", "it is advisable" are only used to describe the embodiments or examples with better effects. It should be understood that they do not constitute a limitation to the protection scope of the present invention.

[0035] In this text, "further", "even further", "especially", etc. are used for descriptive purposes, indicating differences in content, but should not be understood as a limitation to the protection scope of the present invention.

[0036] In this text, "optionally", "optional", "option" mean that it can be either present or absent, that is, it refers to any one of the two parallel options of "present" or "absent". If there are multiple "options" in a technical solution, without special instructions and without contradictions or mutual restrictions, each "option" is independent.

[0037] In the present invention, among the technical features described in an open-ended manner, it includes the closed technical solutions composed of the listed features, and also includes the open technical solutions containing the listed features.

[0038] In the present invention, regarding the numerical interval (that is, the numerical range), without special instructions, the optional numerical values are considered continuous within the above numerical interval, and include the two numerical endpoints (that is, the minimum value and the maximum value) of this numerical range, as well as each numerical value between these two numerical endpoints. Without special instructions, when the numerical interval only refers to the integers within this numerical interval, it includes the two endpoint integers of this numerical range, as well as each integer between the two endpoints. In this text, it is equivalent to directly listing each integer. For example, t is an integer selected from 1 to 10, indicating that t is any integer selected from the integer group composed of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. In addition, when providing multiple range descriptions of features or characteristics, these ranges can be combined. In other words, unless otherwise specified, the ranges disclosed in this text should be understood to include any and all sub-ranges subsumed therein.

[0039] For the temperature parameters in the present invention, without special limitations, it allows both constant temperature treatment and allows fluctuations within a certain temperature range. It should be understood that the so-called constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument. It is allowed to fluctuate within a range such as ±5°C, ±4°C, ±3°C, ±2°C, ±1°C.

[0040] In the present invention, %(w / w) and wt% both represent weight percentage, %(v / v) refers to volume percentage, and %(w / v) refers to mass-volume percentage.

[0041] All the documents mentioned in the present invention are incorporated herein by reference as if each document were individually incorporated by reference. Unless it conflicts with the inventive purpose and / or technical solution of the present application, the cited documents related to the present invention are incorporated by reference in their entirety and for all purposes. When referring to cited documents in the present invention, the definitions of relevant technical features, terms, nouns, phrases, etc. in the cited documents are also incorporated by reference. When referring to cited documents in the present invention, the examples and preferred modes of the relevant technical features cited can also be incorporated into the present application as references, but only to the extent that the present invention can be implemented. It should be understood that when the cited content conflicts with the description in the present application, the present application shall prevail or be amended adaptively according to the description in the present application.

[0042] The treatment of intestinal flora imbalance with traditional Chinese medicine has been sufficiently developed and the theoretical system has become increasingly mature. Based on the syndrome differentiation and treatment of traditional Chinese medicine and the adjustment of medication rules, combined with modern medical knowledge and scientific and technological means, in-depth research on the mechanism of action of traditional Chinese medicine can promote the close combination of clinical and basic research and provide a basis for the further development of the treatment of intestinal flora imbalance. According to the basic principles of the overall concept and syndrome differentiation and treatment in the process of traditional Chinese medicine treatment, intestinal flora imbalance is classified into the category of "diarrhea". Traditional Chinese medicine theory holds that the main cause of diarrhea is spleen deficiency and dampness excess, and the pathogenesis lies in the disorder of the transportation and transformation functions of the spleen and stomach, and the loss of the functions of the intestine to distinguish clear and turbid and conduct. At present, traditional Chinese medicine is clinically used to intervene in intestinal flora and has achieved good results.

[0043] Traditional Chinese medicine treatment cases for intestinal flora imbalance include:

[0044] CN115177694 describes a plant composite extract, which includes: an extract of Danggui Niantong Decoction; and a golden thread lotus extract. The plant composite extract is used to treat and / or prevent hyperuricemia or gout, to treat and / or improve intestinal flora imbalance caused by hyperuricemia, to treat and / or improve uric acid metabolism disorder caused by hyperuricemia, to treat and / or improve liver damage caused by hyperuricemia, to treat and / or improve kidney damage caused by hyperuricemia, to reduce the expression level of inflammatory factors that cause gout attacks, to inhibit xanthine oxidase activity, to increase the abundance of beneficial bacteria, and to reduce the abundance of harmful bacteria or conditional pathogens; wherein, the inflammatory factors that cause gout attacks include IL-β; the beneficial bacteria include Lachnospiraceae_NK4A136_group, Akkermans ia, Faecalibaculum, norank_f__Eubacterium_coprostanoligenes_group, NK4A214_group, norank_f__Coriobacteriales_Incertae_Sedis and Adlercreutzia; the harmful bacteria include at least one of Escherichia-Shigella and Helicobacter; the conditional pathogens include at least one of Bacteroides, Butyricimonas and Prevotellaceae_NK3B31_group.

[0045] CN104645294A records a Chinese medicine composition for treating diarrhea in children, which is prepared by extracting the following Chinese medicines in weight: 50-250 parts of Atractylodes lancea, 50-250 parts of Poria cocos, 25-120 parts of Paojiang, 50-250 parts of stewed Alpinia oxyphylla, 100-500 parts of raw malt, and 10-60 parts of Amomum villosum. The Chinese medicine composition of the present invention has the effects of treating diarrhea in children, protecting the intestinal mucosal barrier, and regulating intestinal flora. Experimental studies have confirmed that it has significant therapeutic effects on treating intestinal mucosal damage and intestinal flora imbalance caused by diarrhea in children and chronic spleen deficiency diarrhea, and is an ideal medicine for treating intestinal mucosal barrier damage and intestinal flora imbalance caused by diarrhea in children and spleen deficiency diarrhea.

[0046] CN114767810A discloses a traditional Chinese medicine composition for treating acute lung injury, which is prepared from the following raw materials by weight: 5-20 parts of raw Ephedra, 5-20 parts of Rhizoma Cimicifugae, 5-30 parts of Angelica sinensis, 5-30 parts of Anemarrhena asphodeloides, 5-40 parts of Polygonatum odoratum, 5-30 parts of Scutellaria baicalensis, 5-30 parts of Paeonia lactiflora, 5-40 parts of Asparagus cochinchinensis, 5-40 parts of Artemisia annua, 5-40 parts of Carapax Trionycis, 5-20 parts of Tsaoko fruit, 5-30 parts of Magnolia officinalis, 5-50 parts of Gypsum Fibrosum, 5-40 parts of Atractylodes lancea, 5-20 parts of Glycyrrhiza uralensis. The present invention prevents pathogen colonization by regulating the structural distribution and composition of the intestinal flora and upregulating the body's immune response. It improves the imbalance of the intestinal flora, increases the beneficial flora that can produce short-chain fatty acids, inhibits the harmful flora, and plays a positive role in adjusting the flora. It has an obvious therapeutic effect on acute lung injury and has good clinical application prospects. Cause of flora imbalance: The composition of the intestinal flora in rats with intestinal ischemia-reperfusion lung injury changes.

[0047] CN106070607A discloses a pineapple-flavored heat-clearing brown milk beverage, which is prepared from the following raw materials by weight: 40-50 parts of skim milk powder, 20-30 parts of tartary buckwheat bran, 30-40 parts of pineapple, 10-15 parts of fig, 8-12 parts of balsam pear, 6-8 parts of Trollius chinensis, 2-3 parts of Cortex Moutan, 1-2 parts of Caulis Bambusae in Taeniam, 3-4 parts of Fructus Lilii, 1-2 parts of mogroside, 1-2 parts of citric acid, appropriate amount of concentrated whey protein, appropriate amount of stabilizer, appropriate amount of strain; The present invention adds natural raw materials such as pineapple and balsam pear, which have the effects of clearing heat and promoting diuresis, moistening the intestines and relieving constipation, etc. It not only enriches the texture and taste of the product, meets the pursuit of modern people for nutritious, healthy, green and safe food, but also has good health care effects. The finished brown lactic acid bacteria beverage at room temperature can maintain a uniform and stable product tissue state, good fluidity, no water separation and precipitation within a half-year shelf life, and can maintain a fresh and smooth taste. Long-term drinking can improve the imbalance of the intestinal flora and is suitable for people with constipation, obesity, diabetes, etc.

[0048] CN115068554A records an antibiotic substitute and a preparation method thereof. The antibiotic substitute is prepared from the following raw materials in parts by weight: 50-60 parts of sulfa, 10-20 parts of Pulsatilla scabra, 10-20 parts of Coptis chinensis, 10-20 parts of Phellodendron chinense, 5-10 parts of Angelica sinensis, 7-8 parts of Honeysuckle, 15-20 parts of Licorice, 10-15 parts of Platycladus orientalis leaves, 8-12 parts of Terminalia chebula, 10-15 parts of Polygonatum sibiricum, 10-15 parts of Patchouli, 15-20 parts of Anemarrhena asphodeloides, 5-10 parts of Menthus fragrans, and 5-10 parts of Houttuynia cordata. By using the commonly used antibiotic sulfonamide and Chinese medicinal materials to prepare antibiotic substitutes, the dosage of commonly used antibiotics is reduced, ensuring that the efficacy of the drugs is normal, avoiding the development of drug resistance in Escherichia coli in patients due to long-term use of sulfonamide, and shortening the patient's treatment cycle. At the same time, the drug has many components and more targets, which can further prevent Escherichia coli from developing drug resistance. The addition of Chinese medicinal materials can effectively alleviate the damage of sulfonamide to the beneficial flora in the patient's intestines, avoiding the imbalance of the patient's intestinal flora.

[0049] However, those skilled in the art know that different treatment plans are required for different intestinal flora disorders, and that specific intestinal flora disorders cannot be simply treated by referring to other intestinal flora disorders. In addition, those skilled in the art know that Chinese medicine emphasizes holistic use, and different compound prescriptions with the same individual medicinal materials do not necessarily have the same efficacy.

[0050] Based on the actual application of traditional Chinese medicine, the present application has conducted a long-term study on the traditional Chinese medicine composition and found that it can improve the intestinal flora imbalance, thereby providing the application of the traditional Chinese medicine composition in the preparation of a drug for improving intestinal flora imbalance;

[0051] The effective ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 80-120 parts of black-striped snake, 1800-2200 parts of peony bark, 800-1200 parts of phellodendron, 8-12 parts of bezoar, 7800-8200 parts of atractylodes, 800-1200 parts of siler, 1800-2200 parts of angelica, 0.8-1.2 parts of snake bile, 13000-18000 parts of cnidium monnieri, 1800-2200 parts of sophora flavescens, and 80-120 parts of ginseng root.

[0052] In the Chinese medicine composition of the present application, the bezoar may be a synthetic bezoar.

[0053] In one example, the effective ingredients of the Chinese medicine composition are prepared from the following raw materials in parts by mass: 100 parts of black-necked snake, 2000 parts of peony bark, 1000 parts of phellodendron, 10 parts of bezoar, 8000 parts of atractylodes, 1000 parts of siler, 2000 parts of angelica, 1 part of snake bile, 15000 parts of cnidium monnieri, 2000 parts of sophora flavescens, and 100 parts of ginseng root.

[0054] The dosage form of the drug in this application is not particularly limited, and it can be prepared into a suitable dosage form according to the needs of clinical applications, etc., such as: pills, granules, suppositories, capsules, tablets, dripping pills, injections, powders, etc.

[0055] The traditional Chinese medicine composition can be prepared into pills by the following preparation method:

[0056] Of the above eleven herbs, take 88% of Atractylodes lancea, 93% of Cnidium monnieri, 50% of Sophora flavescens and Paeonia suffruticosa, add water and decoct, filter, concentrate the filtrate to an appropriate amount. Separately, Phellodendron amurense, Angelica sinensis, Radix Ginseng Fibrosa, Zaocys dhumnades and the remaining Atractylodes lancea, Sophora flavescens, Cnidium monnieri and Paeonia suffruticosa are pulverized into coarse powder, mixed evenly with the concentrated liquid, dried, pulverized into fine powder, sieved, and ground and mixed evenly with synthetic bezoar and snake bile. Make pills with water, coat, polish, and dry to obtain Wusha Zhiyang Pills.

[0057] Wusha Zhiyang Pills are composed of Zaocys dhumnades (fried with white wine), Saposhnikovia divaricata, Cnidium monnieri, Sophora flavescens, Phellodendron amurense, Atractylodes lancea (soaked), Radix Ginseng Fibrosa, Paeonia suffruticosa, snake bile, artificial bezoar, and Angelica sinensis, and have the effects of nourishing blood, expelling wind, drying dampness and relieving itching. Clinically, it is mainly used for the treatment of inflammatory skin diseases such as urticaria, pruritus cutis, dermatitis and eczema. At present, there is no clear data showing the application of Wusha Zhiyang Pills in intestinal flora imbalance, which limits the effective utilization of Wusha Zhiyang Pills. This application increases the indications of Wusha Zhiyang Pills and provides a new drug option for the treatment of patients with clinical intestinal flora imbalance diseases.

[0058] Optionally, the intestinal flora imbalance includes a decrease in the relative abundance of the Bacteroidota phylum flora, and an increase in the relative abundances of the Campilobacterota phylum and Desulfobacterota phylum flora.

[0059] Optionally, the intestinal flora imbalance includes a decrease in the relative abundances of the Muribaculaceae family and Bacteroidaceae family flora.

[0060] Optionally, the intestinal flora imbalance includes a decrease in the relative abundance of the Bacteroides genus flora, and an increase in the relative abundances of the Lactobacillus genus and Odoribacter genus flora.

[0061] Optionally, the intestinal flora imbalance includes, but is not limited to, the intestinal flora imbalance caused by ulcerative colitis or / and constipation.

[0062] In this article, "relative" refers to relative to the normal level.

[0063] "Improve" means that under the condition of giving an "effective dose", the drug has a positive effect and can play roles such as cure and treatment.

[0064] In this text, the "therapeutically effective amount" refers to the dosage of a preparation, which is the minimum amount necessary to improve, cure, or treat one or more symptoms of a disease or disorder. The "therapeutically effective amount" will vary depending on the specific condition being treated, the disease, disorder, or condition and its severity, as well as the age, weight, physical condition, and reactivity of the individual being treated. Therefore, one or more of these parameters can be used to select and adjust the therapeutically effective amount of Wusha Zhiyang Pills.

[0065] In this text, in the present invention, a "subject" refers to a patient who takes a drug.

[0066] In this text, a "subject" is an animal, preferably a mammal, more preferably a human. Subjects include, but are not limited to, patients with diseases, disorders, and / or symptoms. The subjects in the present invention are preferably mammals. The term "mammal" mainly refers to warm-blooded vertebrate mammals, including, but not limited to: cats, dogs, rabbits, bears, foxes, wolves, monkeys, deer, rats (such as rats, mice), pigs, cows, sheep, horses, humans, etc., preferably primates, more preferably humans.

[0067] The embodiments of the present invention will be described in detail below in conjunction with examples. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention. For the experimental methods without specific conditions indicated in the following examples, the guidance given in the present invention is preferably referred to, and it can also be carried out according to the experimental manuals or conventional conditions in the art, or according to the conditions recommended by the manufacturer, or by referring to the experimental methods known in the art.

[0068] In the following specific examples, for the measurement parameters of raw material components, if there is no special indication, there may be slight deviations within the weighing accuracy range. For temperature and time parameters, acceptable deviations caused by instrument test accuracy or operation accuracy are allowed.

[0069] 1. Experimental method

[0070] Twenty-four male BALB / c mice aged 6 - 8 weeks were randomly divided into 4 groups: normal control group (Control), model control group (DNCB), low-dose Wusha Zhiyang Pills group (WSL), and high-dose Wusha Zhiyang Pills group (WSH), with 6 mice in each group. The mice in the WSL and WSH groups were intragastrically administered Wusha Zhiyang Pills (3.075 g / kg / d, 6.150 g / kg / d) respectively. The Control group and the DNCB group were intragastrically administered an equal volume of distilled water.

[0071] The establishment of the animal model depends on depilation on the back of mice. On day 0 and day 4, 1 wt% DNCB was used to sensitize the depilated area on the back and the right ear of mice (DNCB was dissolved in a mixture of acetone and olive oil, and the volume ratio of acetone to olive oil was 3:1). From day 8 to day 30, the depilated area on the back and the right ear of mice were repeatedly challenged with the same volume of 0.6 wt% DNCB once every two days, so as to induce the disorder of the intestinal flora in mice. After the successful establishment of the model, the low-dose group of Wusha Zhiyang Pills (WSL) and the high-dose group of Wusha Zhiyang Pills (WSH) were respectively given Wusha Zhiyang Pills. The Control group was dripped with a mixture of equal volume of acetone and olive oil on the depilated area on the back and the right ear of mice for blank control.

[0072] After the modeling was completed, the feces of mice were collected for 16S rRNA gene sequencing to analyze the effect of Wusha Zhiyang Pills on the microorganisms in the intestinal flora of mice.

[0073] 2. Experimental results

[0074] (1) PCA analysis of the Beta diversity of the intestinal flora of mice by Wusha Zhiyang Pills

[0075] PCA analysis of the Beta diversity of the intestinal flora of mice in different groups found that the inter-group difference between the model group and the Control group was very obvious, indicating that the composition of the intestinal flora of the model mice caused by DNCB was significantly changed. The distances between the low-dose and high-dose groups of Wusha Zhiyang Pills (WSL, WSH) and the Control group were similar, indicating that giving Wusha Zhiyang Pills could effectively regulate the intestinal flora of mice and return it to the normal level. See Figure 1 .

[0076] (2) Effect of Wusha Zhiyang Pills on the relative abundance of the phylum level of the intestinal flora of mice

[0077] Analysis of the relative abundance of the phylum of the intestinal flora of mice found that compared with the Control group, the relative abundance of Bacteroidota in the intestinal flora disorder model group caused by DNCB was significantly reduced; compared with the model group, after giving Wusha Zhiyang Pills, the relative abundance of Bacteroidota showed an obvious callback, and the difference was statistically significant. As a phylum of bacteria beneficial to the host, Bacteroidota can widely digest dietary fiber polysaccharides and glycans, improve digestion ability, and its metabolite flavonoids also have obvious anti-inflammatory and antioxidant functions. The abundances of the Campilobacterota and Desulfobacterota phyla in the intestinal flora disorder model group caused by DNCB were also significantly increased. After giving Wusha Zhiyang Pills, the abundances of these two phyla showed an obvious callback, and the difference was statistically significant.

[0078] See Figure 2 andFigure 3 .

[0079] (3) Effect of Wushe Zhiyang Pills on the relative abundance of bacterial families in the intestinal flora of mice

[0080] Subsequently, the relative abundance of the bacterial family level in the intestinal flora of mice was analyzed. The experimental results showed that compared with the Control group, the relative abundance of Muribaculaceae in the intestinal flora disorder model group caused by DNCB was significantly reduced; after the administration of Wushe Zhiyang Pills, the relative abundance of Muribaculaceae showed a significant callback, and the difference was statistically significant. Muribaculaceae belongs to the family of Muribacteraceae, which is a beneficial bacterium. It is the dominant flora in the intestine of mice. It is rich in enzymes that decompose carbohydrates and can metabolize short-chain fatty acids (SCFAs), promote the growth and development of intestinal epithelial cells, and promote the secretion of anti-inflammatory factors, regulate intestinal microbiota, and relieve constipation symptoms. Similarly, the Bacteroidaceae in the intestinal flora disorder model group caused by DNCB showed a decrease to varying degrees; after the administration of Wushe Zhiyang Pills, the Bacteroidaceae bacterial family showed a significant callback, and the difference was statistically significant. Studies have found that Bacteroidaceae can produce a metabolite called indole-3-acetic acid (IAA) in the intestine, and IAA can effectively activate bacterial metabolic pathways and inhibit the formation of pathogenic and drug-resistant bacteria in the body.

[0081] See Figure 4 and Figure 5 .

[0082] (4) Effect of Wushe Zhiyang Pills on the relative abundance of bacterial genus levels in the intestinal flora of mice

[0083] Analysis of the relative abundances of mouse gut microbiota at the genus level revealed that, compared with the Control group, the relative abundance of Bacteroides in the gut microbiota disorder model group induced by DNCB was significantly decreased; after treatment with Wusha Zhiyang Pills, the relative abundance of Bacteroides showed a significant callback, and the difference was statistically significant. Bacteroides is one of the most common types of resident microbiota in the gut and is also an important keystone genus in the gut composition. Studies have found that its polysaccharide utilization locus (PUL) can mediate the process of cross-feeding among species to help humans obtain essential nutrients. In addition, it can also regulate immunity through capsular polysaccharide A; at the same time, Bacteroides can produce short-chain fatty acids to maintain gut homeostasis. In contrast, Odoribacter is a Gram-negative, obligately anaerobic, non-spore-forming symbiotic bacterium, and studies have found that it can promote the occurrence and development of gut inflammation. The relative abundances of Lactobacillus and Odoribacter in the gut microbiota disorder model group induced by DNCB were significantly increased; after treatment with Wusha Zhiyang Pills, the relative abundances of Lactobacillus and Odoribacter were significantly decreased, and the difference was statistically significant.

[0084] See Figure 6 and Figure 7 。

[0085] The above experimental results indicate that Wusha Zhiyang Pills can significantly alleviate gut microbiota dysbiosis in model mice, providing a new drug option for the treatment of clinical patients with gut microbiota dysbiosis.

[0086] The technical features of the above-described embodiments and examples can be combined in any suitable manner. For the sake of brevity of description, not all possible combinations of the technical features in the above embodiments and examples are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered to be within the scope described in this specification.

[0087] The above-described embodiments merely represent several implementation manners of the present invention, facilitating the specific and detailed understanding of the technical solution of the present invention. However, it should not be construed as a limitation on the protection scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several deformations and improvements can still be made, and these all fall within the protection scope of the present invention. In addition, it should be understood that after reading the above teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and the equivalent forms obtained also fall within the protection scope of this application. It should also be understood that the technical solutions obtained by those skilled in the art through logical analysis, reasoning or limited experiments based on the technical solution provided by the present invention are all within the protection scope of the appended claims of the present invention. Therefore, the protection scope of this invention patent shall be subject to the content of the appended claims, and the specification and drawings can be used to explain the content of the claims.

Claims

1. Use of a traditional Chinese medicine composition in the preparation of a drug for improving intestinal flora imbalance; The active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by mass: Zaocys dhumnades 80 - 120 parts, Cortex Moutan 1800 - 2200 parts, Phellodendron amurense Rupr. 800 - 1200 parts, Calculus Bovis 8 - 12 parts, Atractylodes lancea (Thunb.) DC. 7800 - 8200 parts, Saposhnikovia divaricata (Turcz.) Schischk. 800 - 1200 parts, Angelica sinensis (Oliv.) Diels 1800 - 2200 parts, snake bile 0.8 - 1.2 parts, Fructus Cnidii 13000 - 18000 parts, Sophora flavescens Ait. 1800 - 2200 parts, and Radix Ginseng Fibra 80 - 120 parts; The intestinal flora imbalance includes: The relative abundances of the Campilobacterota and Desulfobacterota phylum flora increase, the relative abundance of the Muribaculaceae family decreases, the relative abundance of the Bacteroides genus flora decreases, and the relative abundances of the Lactobacillus genus and Odoribacter genus flora increase; The intestinal flora imbalance is caused by DNCB.

2. The use according to claim 1, wherein, the active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by mass: Zaocys dhumnades 100 parts, Cortex Moutan 2000 parts, Phellodendron amurense Rupr. 1000 parts, Calculus Bovis 10 parts, Atractylodes lancea (Thunb.) DC. 8000 parts, Saposhnikovia divaricata (Turcz.) Schischk. 1000 parts, Angelica sinensis (Oliv.) Diels 2000 parts, snake bile 1 part, Fructus Cnidii 15000 parts, Sophora flavescens Ait. 2000 parts, and Radix Ginseng Fibra 100 parts.

3. The use according to claim 1 or 2, wherein, the dosage form of the drug is pills, granules, capsules, tablets or powders.

4. The use according to claim 1 or 2, wherein, the subjects of the drug are mammals.

5. The use according to claim 4, wherein, the mammal is a human.

6. The use according to claim 4, wherein, the mammal is a mouse.

7. The use according to claim 6, wherein, the mammal is a small mouse.

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