Application of Zhangyanming tablets in the preparation of drugs to improve intestinal flora imbalance

Abstract

This application relates to the field of biomedical technology, and specifically to the application of Zhangyanming tablets in the preparation of drugs to improve intestinal flora imbalance. The Zhangyanming tablets comprise: 20-30 parts of Acorus tatarinowii, 30-40 parts of Cassia tora seed, 30-40 parts of Cistanche deserticola, 30-40 parts of Pueraria lobata root, 30-40 parts of Celosia argentea seed, 40-50 parts of Codonopsis pilosula root, 30-40 parts of Vitex trifolia fruit, 40-50 parts of Lycium barbarum fruit, and 30... The formula comprises: ~40 parts Plantago asiatica, 40-50 parts Paeonia lactiflora, 20-30 parts Cornus officinalis, 20-30 parts Glycyrrhiza uralensis, 60-70 parts Cuscuta chinensis, 1-10 parts Cimicifuga foetida, 30-40 parts Prunus armeniaca seed, 30-40 parts Chrysanthemum morifolium, 30-40 parts Buddleja officinalis, 30-40 parts Ligusticum chuanxiong, 30-40 parts Polygonatum sibiricum (processed with wine), 60-70 parts Rehmannia glutinosa (processed), 30-40 parts Phellodendron chinense, and 40-50 parts Astragalus membranaceus. The technical solution of this application has the advantages of wider clinical applicability, better efficacy, lower cost, and fewer side effects.

Description

Technical Field

[0001] This application relates to the field of biomedical technology, and in particular to the application of Zhangyanming tablets in the preparation of drugs to improve intestinal flora imbalance. Background Technology

[0002] The gut microbiota is a complex ecological community of trillions residing in the human gut. Through their collective metabolic activities and interactions with the host, they influence the host's normal physiological functions and disease susceptibility. Gut microbes participate in immune regulation and nutritional metabolism and are closely related to aging.

[0003] The gut of a healthy adult contains five main phyla of bacteria: Bacteroides, Firmicutes, Actinomycetes, Proteus, and Verrucous microorganisms, with Bacteroides and Firmicutes being the most prevalent. Not all gut microbiota are beneficial to the human body; some, like Bifidobacteria and Lactobacilli, are considered beneficial bacteria. Bacteria such as Staphylococcus aureus and hemolytic streptococci, which competitively inhibit the growth and reproduction of beneficial bacteria, are called pathogenic bacteria. Furthermore, there is a class of bacteria that are harmful to the human body only under specific conditions, such as Escherichia coli and Proteus; these are called opportunistic pathogens. When the location or surrounding environment of these bacteria in the gut changes, they proliferate rapidly, disrupting the balance of the gut microbiota and causing various clinical diseases, a condition known as gut microbiota dysbiosis.

[0004] Currently, methods for regulating gut microbiota mainly include probiotic preparations, prebiotic preparations, fecal microbiota transplantation (FMT), and traditional Chinese medicine treatment. Probiotic preparations primarily consist of beneficial bacteria in the human body, namely, beneficial bacteria that contribute to physiological and immune functions in the gut. These can be live bacteria, dead bacteria, components, or products. Probiotics require stringent preservation conditions, resulting in high costs. Furthermore, probiotic treatment for gut microbiota imbalance can cause adverse reactions in some patients, such as bloating, constipation, and migraines. Prebiotic preparations refer to substances that selectively stimulate or promote the colonization, growth, or activation of one or more physiological bacteria in the host's intestinal mucosa. Prebiotics are not very effective when used alone and do not have inhibitory effects on opportunistic pathogens or pathogenic bacteria. Fecal microbiota transplantation involves transplanting functional bacteria from the feces of healthy individuals into the gastrointestinal tract of a patient to rebuild a normally functioning gut microbiota, thereby treating gut microbiota imbalance. However, the exact efficacy of FMT for gut microbiota imbalance remains unclear, and there are risks of multidrug-resistant bacterial infections and death. Compared to the previous three methods, traditional Chinese medicine (TCM) treatment of gut microbiota imbalance has seen significant development, and its theoretical system has matured. The TCM principle of Yin-Yang balance in disease treatment aligns with the ecological balance theory of gut microbiota. TCM can alter the overall function of the gut microbiota by regulating the types and quantities of dominant bacteria, thus interfering with the body's absorption and utilization of substances and influencing overall health. Furthermore, the effectiveness of TCM in the body requires the gut microbiota to break down and metabolize the drugs, enabling the utilization of their active ingredients and achieving therapeutic effects.

[0005] Currently, there are many clinical case reports demonstrating the good therapeutic effects of traditional Chinese medicine on diseases accompanied by intestinal flora imbalance. However, because traditional Chinese medicine emphasizes holistic treatment and syndrome differentiation, different traditional Chinese medicine formulas are provided for different diseases in the reported cases. Therefore, patients with intestinal flora imbalance whose symptoms are not yet clear cannot arbitrarily refer to and adopt the publicly available treatment methods.

[0006] This traditional Chinese medicine compound (compared to the trade name Zhangyanming Pian) is composed of Acorus tatarinowii, Cassia seed, Cistanche deserticola, Pueraria lobata, Celosia argentea, Codonopsis pilosula, Vitex trifolia, Lycium barbarum, Plantago asiatica, Paeonia lactiflora, Cornus officinalis, Glycyrrhiza uralensis, Cuscuta chinensis, Cimicifuga foetida, Prunus armeniaca seed, Chrysanthemum morifolium, Buddleja officinalis, Ligusticum chuanxiong, Polygonatum sibiricum, Rehmannia glutinosa, Phellodendron chinense, and Astragalus membranaceus. It has the effects of tonifying the liver and kidneys, clearing away cataracts and improving vision. Clinically, it is used for early-stage and middle-aged and elderly cataracts. The ingredients of this formula are mild and have few side effects. Developing its further medicinal uses will help expand the application range of traditional Chinese medicine and greatly shorten the development time and research costs. Summary of the Invention

[0007] During a series of activity studies on Zhangyanming tablets, this application unexpectedly discovered its excellent regulatory effect in improving intestinal flora imbalance. Based on this, it provides the application of Zhangyanming tablets in the preparation of drugs for improving intestinal flora imbalance. Zhangyanming tablets include: 20-30 parts of Acorus tatarinowii, 30-40 parts of Cassia tora, 30-40 parts of Cistanche deserticola, 30-40 parts of Pueraria lobata, 30-40 parts of Celosia argentea, 40-50 parts of Codonopsis pilosula, and 30-40 parts of other herbs. 40-50 parts of Vitex trifolia, 30-40 parts of Lycium barbarum, 40-50 parts of Plantago asiatica, 20-30 parts of Paeonia lactiflora, 20-30 parts of Cornus officinalis, 20-30 parts of Glycyrrhiza uralensis, 60-70 parts of Cuscuta chinensis, 1-10 parts of Cimicifuga foetida, 30-40 parts of Prunus armeniaca seed, 30-40 parts of Chrysanthemum morifolium, 30-40 parts of Buddleja officinalis, 30-40 parts of Ligusticum chuanxiong, 30-40 parts of Polygonatum sibiricum (processed with wine), 60-70 parts of Rehmannia glutinosa (processed), 30-40 parts of Phellodendron chinense, and 40-50 parts of Astragalus membranaceus.

[0008] The technical solution of this application is conducive to expanding the scope of clinical application and has the advantages of good efficacy, low cost and few side effects.

[0009] In one embodiment, the blemish-dispelling tablets include: 22 parts of Acorus tatarinowii, 30 parts of Cassia tora, 37 parts of Cistanche deserticola, 37 parts of Pueraria lobata, 30 parts of Celosia argentea, 48 parts of Codonopsis pilosula, 30 parts of Vitex trifolia, 48 parts of Lycium barbarum, 37 parts of Plantago asiatica, 45 parts of Paeonia lactiflora, 24 parts of Cornus officinalis, 22 parts of Glycyrrhiza uralensis, 61 parts of Cuscuta chinensis, 7 parts of Cimicifuga foetida, 37 parts of Prunus armeniaca seed, 37 parts of Chrysanthemum morifolium, 37 parts of Buddleja officinalis, 30 parts of Ligusticum chuanxiong, 37 parts of Polygonatum sibiricum (processed with wine), 61 parts of Rehmannia glutinosa (processed), 30 parts of Phellodendron chinense, and 48 parts of Astragalus membranaceus.

[0010] In one embodiment, the gut microbiota dysbiosis includes:

[0011] The relative abundance of Bacteroidetes and Verrucous microbes increased, while the relative abundance of Firmicutes decreased; and / or,

[0012] The ratio between Firmicutes and Bacteroidetes is reduced; and / or,

[0013] The relative abundance of Clostridium vadinBB60 and Rumenaceae decreased, while the relative abundance of Muribaculaceae increased; and / or,

[0014] The relative abundance of *Enterobacter* spp. is increased; and / or,

[0015] The relative abundance of the genus *xylanophilum* and the genus *Ospreys* decreased.

[0016] In one embodiment, the intestinal flora imbalance is caused by an intestinal disease, and the traditional Chinese medicine composition is used to prepare a drug for preventing and treating the intestinal disease.

[0017] In one embodiment, the intestinal disease includes at least one of megacolon, colitis, and constipation.

[0018] In one embodiment, the drug is a solid dosage form.

[0019] In one embodiment, the solid dosage form is selected from ordinary tablets, dispersible tablets, sustained-release tablets, capsules, granules, or powders.

[0020] In one embodiment, the drug contains an effective amount of the traditional Chinese medicine composition.

[0021] In one embodiment, the subject of the drug is a mammal.

[0022] In one embodiment, the subject of the drug is a mouse or a human.

[0023] The application of the Zhangyanming tablets in this application in the preparation of drugs to improve intestinal flora imbalance overcomes the shortcomings of existing traditional Chinese medicine treatments that are limited to treating specific diseases and causing intestinal flora imbalance. It can exert multi-target effects through multiple groups, intervene in the dominant bacteria in the intestine, adjust the intestinal flora structure, and improve intestinal flora imbalance, making it more widely and convenient to use in clinical practice.

[0024] The Zhangyanming tablets in this application are composed of 22 kinds of pure herbal medicines. They have few toxic side effects, are not likely to cause drug dependence in patients, are low in cost, and can be widely promoted. They provide an effective and low-side-effect treatment method for adjusting the intestinal microecology and improving intestinal flora imbalance in traditional Chinese medicine clinical practice. Attached Figure Description

[0025] To more clearly illustrate the technical solutions in the specific embodiments of this application or the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0026] Figure 1 The results of PCA analysis of the beta diversity of gut microbiota in mice in different groups (NC group, BCA group, ZYMT group) in Example 1 of this application;

[0027] Figure 2 This is a heatmap showing the relative abundance of different phyla of gut microbiota in different groups of mice (NC group, BCA group, ZYMT group) in Example 1 of this application;

[0028] Figure 3 This is a bar chart showing the relative abundance of key gut microbiota phyla in different groups of mice (NC group, BCA group, ZYMT group) in Example 1 of this application. Bacteroidota abundance refers to the relative abundance of Bacteroidetes, Verrucomicrobiota abundance refers to the relative abundance of Verrucomicrobiota, and Firmicutes abundance refers to the relative abundance of Firmicutes.

[0029] Figure 4 This is a heatmap showing the relative abundance of different gut microbiota families in different groups of mice (NC group, BCA group, ZYMT group) in Example 1 of this application;

[0030] Figure 5 This is a bar chart showing the relative abundance of key gut microbiota families in different groups of mice (NC group, BCA group, ZYMT group) in Example 1 of this application. Muribaculaceae abundance refers to the relative abundance of Muribaculaceae family, Ruminococcaceae abundance refers to the relative abundance of Ruminocactaceae family, and Clostridia_vadinBB60_groupabundance refers to the relative abundance of vadinBB60 group.

[0031] Figure 6 This is a heatmap showing the relative abundance of different gut microbiota genera in different groups of mice (NC group, BCA group, ZYMT group) in Example 1 of this application;

[0032] Figure 7This is a bar chart showing the relative abundance of key gut microbiota genera in different groups of mice (NC group, BCA group, ZYMT group) in Example 1 of this application. Muribaculum abundance refers to the relative abundance of the genus *Muribaculum*, [Eubacterium]_xylanophilum_group abundance refers to the relative abundance of the genus *Eubacterium*, and Oscillibacter abundance refers to the relative abundance of the genus *Oscillibacter*. Detailed Implementation

[0033] The present application is further described below with reference to embodiments and examples. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the application. Furthermore, it should be understood that after reading the teachings of this application, those skilled in the art can make various alterations or modifications to this application, and these equivalent forms also fall within the protection scope of the appended claims.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0035] the term

[0036] Unless otherwise stated or in case of contradiction, the terms or phrases used herein shall have the following meanings:

[0037] In this article, "BCA" refers to benzalkonium chloride. In specific experiments, subjects are treated with benzalkonium chloride solution, which typically has a mass concentration of 0.2%.

[0038] "PCA analysis" refers to the use of variance decomposition to reflect the differences between multiple sets of data on a two-dimensional or three-dimensional coordinate graph. The coordinate axes are two or three characteristic values ​​that can best reflect the variance. For example, the more similar the sample composition, the closer they are reflected in the PCA graph.

[0039] The phyla, families, and genera of fungi mentioned in this article, along with their English names, are as follows:

[0040] Bacteroidota: Phylum Bacteroides.

[0041] Verrucomicrobiota: Phylum Verrucomicrobiota.

[0042] Firmicutes: Phylum Firmicutes.

[0043] Clostridia_vadinBB60_group: Clostridiales vadinBB60 group.

[0044] Ruminococcaceae: Ruminocacti family, whose main fermentation metabolite is acetic acid. The abundance of this genus has been shown to be positively correlated with intestinal motility.

[0045] Muribaculaceae (also known as Mucispirillum) is a family of bacteria that includes some symbiotic gut bacteria that produce intestinal mucus. It was initially classified as part of the Bacteroidaceae family. These bacteria play important physiological functions in the gut, such as participating in food digestion and nutrient absorption, and regulating the immune system. Muribaculaceae is a newly established family name. It was formerly known as the S24-7 family and is mainly associated with various dietary therapies, host conditions, or rodent colonization processes.

[0046] Muribaculum: Enterobacterium muscarinii;

[0047] Eubacterium: A genus of bacteria found in the colon of healthy individuals. It is one of the core genera of the human gut microbiota and plays an important role in nutritional metabolism and maintaining intestinal balance.

[0048] [Eubacterium]_xylanophilum_group: Eubacterium xylanophilum, belonging to the family Trichophyceae in the phylum Firmicutes. Its abundance is positively correlated with the degree of intestinal homeostasis, and its presence is related to the production of branched-chain amino acids and short-chain fatty acids.

[0049] Oscillibacter: A genus of bacteria associated with reduced cholesterol levels in feces and plasma. It possesses cholesterol metabolism capabilities, including glycosylation and dehydrogenation. These bacteria can metabolize cholesterol in the gut, thereby helping to lower host cholesterol levels and cardiovascular disease risk, and are beneficial for lipid balance and cardiovascular health.

[0050] F / B: The ratio of the relative abundance of Firmicutes to Bacteroidota. An abnormal value of this ratio reflects potential pathological changes. For example, an abnormal increase in the abundance of a specific Firmicutes or Bacteroidota species can lead to obesity and intestinal inflammation, respectively.

[0051] The term "and / or" as used herein includes any one of two or more related listed items, as well as any and all combinations of the related listed items. These arbitrary and all combinations encompass any two related listed items, any more related listed items, or a combination of all related listed items. It should be noted that when at least three items are connected using at least two conjunctions selected from "and / or," "or / and," or "and / or," it should be understood that, in this application, the technical solution undoubtedly includes solutions connected by "logical AND," and also undoubtedly includes solutions connected by "logical OR." For example, "A and / or B" includes three parallel solutions: A, B, and A+B. For example, the technical solution of "A, and / or, B, and / or, C, and / or, D" includes any one of A, B, C, and D (that is, a technical solution that is connected by "logical OR"), as well as any and all combinations of A, B, C, and D, that is, combinations of any two or three of A, B, C, and D, and also combinations of all four of A, B, C, and D (that is, a technical solution that is connected by "logical AND").

[0052] In this document, terms such as "preferred," "better," and "more preferred" are merely descriptions of implementation methods or examples that achieve better results, and should be understood as not constituting a limitation on the scope of protection of this application.

[0053] In this application, terms such as "further," "even further," and "particularly" are used to describe purposes and indicate differences in content, but should not be construed as limiting the scope of protection of this application.

[0054] In this application, the terms "first aspect," "second aspect," "third aspect," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or quantity, nor should they be construed as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first," "second," "third," etc., serve only as a non-exhaustive enumeration and should be understood not to constitute a closed limitation on quantity.

[0055] In this application, the technical features described in an open-ended manner include both closed technical solutions consisting of the listed features and open technical solutions that include the listed features.

[0056] In this application, numerical intervals (i.e., numerical ranges) are involved. Unless otherwise specified, optional numerical distributions within the aforementioned numerical intervals are considered continuous and include the two endpoints (i.e., the minimum and maximum values) of the numerical range, as well as every value between these two endpoints. Unless otherwise specified, when a numerical interval refers only to integers within that interval, it includes the two endpoint integers of the numerical range, as well as every integer between the two endpoints. Furthermore, when multiple ranges are provided to describe features or characteristics, these ranges can be merged. In other words, unless otherwise specified, the ranges disclosed herein should be understood to include any and all subranges to which they are included.

[0057] In this application, "prevention and treatment" includes concepts such as prevention, treatment, and adjunctive treatment.

[0058] In this application, "composition" can be a combination of multiple substances, or more specifically, a combination of substances used together, or a mixture formed by combining substances.

[0059] In this application, "effective dose" refers to the dose by which the corresponding component achieves therapeutic, preventive, alleviating and / or relieving specific diseases, conditions and / or symptoms in a subject. In this application, unless otherwise specified, it refers to the dose by which intestinal ischemia-reperfusion injury is treated, preventive, alleviating and / or relieving.

[0060] In this application, "subject" refers to an animal, preferably a mammal, and more preferably a human. Subjects include, but are not limited to, consumers of food, users of health products, and patients with diseases, conditions, and / or symptoms. Subjects in this application are preferably mammals. The term "mammal" primarily refers to warm-blooded vertebrate mammals, including but not limited to: cats, dogs, rabbits, bears, foxes, wolves, monkeys, deer, mice (such as rats and mice), pigs, cattle, sheep, horses, and humans, preferably primates, and more preferably humans. Taking the subject of steviol disaccharide as an example, it refers to an animal receiving steviol disaccharide or a combination thereof to treat, prevent, alleviate, and / or relieve diseases, conditions, and symptoms.

[0061] In this application, "patient" refers to an animal, preferably a mammal, and more preferably a human. The term "mammal" mainly refers to warm-blooded vertebrate mammals, including but not limited to: such as cats, dogs, rabbits, bears, foxes, wolves, monkeys, deer, rats, pigs, cattle, sheep, horses, and humans, preferably primates, and more preferably humans.

[0062] In this application, "pharmaceutical composition" refers to a composition that has pharmaceutical preventive and / or therapeutic effects and can be used as a pharmaceutical.

[0063] As used herein, "drug" includes any agent, compound, composition, or mixture that provides physiological and / or pharmacological effects in vivo or in vitro, and often provides beneficial effects. The scope of the physiological and / or pharmacological effects produced by the "drug" in vivo is not particularly limited; it may have systemic effects or only local effects. The activity of the "drug" is not particularly limited; it may be an active substance that can interact with other substances or an inert substance that does not interact with other substances.

[0064] As used herein, "therapeutic effective amount" means the amount of a pharmaceutically active ingredient that will elicit a biological or medical response in an individual in relation to a disease, condition, and / or symptom, such as the amount of the compound of this application that brings about a positive physiological and / or pharmacological effect in an individual, including but not limited to reducing or inhibiting enzyme or protein activity or improving symptoms, alleviating conditions, slowing or delaying disease progression, or preventing disease.

[0065] In this application, "pharmaceutically acceptable" means those ligands, materials, compositions, and / or dosage forms that are suitable for administration to patients within the bounds of reasonable medical judgment and that are commensurate with a reasonable benefit / risk ratio.

[0066] In this application, "pharmaceutically acceptable carrier" means a pharmaceutically acceptable material, composition, or medium, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. As used herein, the language "pharmaceutically acceptable carrier" includes buffers compatible with drug administration, sterile water for injection, solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic agents and absorption delay agents, and the like. Each carrier must be "pharmaceutically acceptable" in the sense of compatibility with other components in the formulation and harmlessness to the patient. Suitable examples include, but are not limited to: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch, potato starch and substituted or unsubstituted β-cyclodextrins; (3) cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth gum; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn... Rice oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) phosphate buffer; and (21) other non-toxic compatible substances used in pharmaceutical formulations. In this application, "pharmaceutically acceptable carriers" may be selected from the following range: including but not limited to mannitol, sorbitol, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, cysteine ​​hydrochloride, thioglycolic acid, methionine, vitamin C, disodium EDTA, sodium calcium EDTA, carbonates, acetates, phosphates or aqueous solutions of monovalent alkali metals, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acids, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivatives, cellulose and its derivatives, alginate, gelatin, polyvinylpyrrolidone, glycerol, Tween 80, agar, calcium carbonate, calcium bicarbonate, surfactants, polyethylene glycol, cyclodextrin, phospholipids, kaolin, talc, calcium stearate, and magnesium stearate.

[0067] The first aspect of this application

[0068] The first aspect of this application provides the use of Zhangyanming tablets (also referred to as Traditional Chinese Medicine Composition I) in the preparation of a medicament for improving intestinal flora imbalance (also referred to as Medicinal Drug II). This method overcomes the shortcomings of traditional Chinese medicine treatments that require specific combinations for specific diseases, has a wider range of applications, and is more convenient for clinical use.

[0069] In this application, unless otherwise specified, "Traditional Chinese Medicine Composition I" refers to a traditional Chinese medicine composition containing the following components: Acorus tatarinowii, Cassia tora, Cistanche deserticola, Pueraria lobata, Celosia argentea, Codonopsis pilosula, Vitex trifolia, Lycium barbarum, Plantago asiatica, Paeonia lactiflora, Cornus officinalis, Glycyrrhiza uralensis, Cuscuta chinensis, Cimicifuga foetida, Prunus armeniaca, Chrysanthemum morifolium, Buddleja officinalis, Ligusticum chuanxiong, Polygonatum sibiricum (processed with wine), Rehmannia glutinosa (processed), Phellodendron chinense, and Astragalus membranaceus.

[0070] Specifically, the weight parts of each component are as follows: 20-30 parts of Acorus tatarinowii, 30-40 parts of Cassia tora, 30-40 parts of Cistanche deserticola, 30-40 parts of Pueraria lobata, 30-40 parts of Celosia argentea, 40-50 parts of Codonopsis pilosula, 30-40 parts of Vitex trifolia, 40-50 parts of Lycium barbarum, 30-40 parts of Plantago asiatica, 40-50 parts of Paeonia lactiflora, 20-30 parts of Cornus officinalis, 20-30 parts of Glycyrrhiza uralensis, 60-70 parts of Cuscuta chinensis, 1-10 parts of Cimicifuga foetida, 30-40 parts of Prunus armeniaca seed, 30-40 parts of Chrysanthemum morifolium, 30-40 parts of Buddleja officinalis, 30-40 parts of Ligusticum chuanxiong, 30-40 parts of Polygonatum sibiricum (processed with wine), 60-70 parts of Rehmannia glutinosa (processed), 30-40 parts of Phellodendron chinense, and 40-50 parts of Astragalus membranaceus.

[0071] In one embodiment, the traditional Chinese medicine composition includes: 22 parts of Acorus tatarinowii, 30 parts of Cassia tora, 37 parts of Cistanche deserticola, 37 parts of Pueraria lobata, 30 parts of Celosia argentea, 48 parts of Codonopsis pilosula, 30 parts of Vitex trifolia, 48 parts of Lycium barbarum, 37 parts of Plantago asiatica, 45 parts of Paeonia lactiflora, 24 parts of Cornus officinalis, 22 parts of Glycyrrhiza uralensis, 61 parts of Cuscuta chinensis, 7 parts of Cimicifuga foetida, 37 parts of Prunus armeniaca seed, 37 parts of Chrysanthemum morifolium, 37 parts of Buddleja officinalis, 30 parts of Ligusticum chuanxiong, 37 parts of Polygonatum sibiricum (processed with wine), 61 parts of Rehmannia glutinosa (processed), 30 parts of Phellodendron chinense, and 48 parts of Astragalus membranaceus.

[0072] In one embodiment, the traditional Chinese medicine composition specifically refers to Zhangyanming tablets.

[0073] Gut microbiota dysbiosis, also known as gut microbial imbalance, refers to an imbalance caused by changes in the types, quantities, proportions, or distribution of normal gut microbiota due to various reasons. This imbalance may lead to a variety of gastrointestinal and extraintestinal diseases, causing symptoms such as diarrhea, abdominal pain, and bloating.

[0074] Common causes of gut microbiota dysbiosis include poor dietary habits, antibiotic overuse, and aging. For example, long-term antibiotic use can reduce antibiotic-sensitive bacteria, leading to an overgrowth of drug-resistant bacteria. Furthermore, poor dietary habits can disrupt the balance of gut microbiota; the decrease in beneficial bacteria and the increase in harmful bacteria in the gut of older adults can also lead to dysbiosis. Gut microbiota dysbiosis is also associated with a variety of diseases, including but not limited to inflammatory bowel disease (IBD), type 2 diabetes mellitus (T2DM), autoimmune diseases, mental illnesses, colorectal cancer, irritable bowel syndrome (IBS), and chronic fatigue syndrome.

[0075] In one embodiment, gut microbiota dysbiosis includes:

[0076] The relative abundance of Bacteroidota and Verrucomicrobiota phyla increased, while the relative abundance of Firmicutes phylum decreased; and / or,

[0077] The ratio between Firmicutes and Bacteroidota phyla is reduced; and / or,

[0078] The relative abundance of Clostridium vadinBB60 group and Ruminococcaceae family decreased, while the relative abundance of Muribacaceae family increased; and / or,

[0079] The relative abundance of the genus *Muribaculum* is increased; and / or,

[0080] The relative abundance of the Eubacterium genus xylanophilum and the Oscillibacter genus is reduced.

[0081] In one embodiment, intestinal flora imbalance is caused by intestinal diseases, and the traditional Chinese medicine composition is used to prepare a drug for preventing and treating intestinal diseases.

[0082] In one embodiment, the intestinal disease includes at least one of megacolon, colitis, and constipation.

[0083] In some embodiments, drug II is a solid dosage form.

[0084] In some embodiments, the solid dosage form is selected from ordinary tablets, dispersible tablets, sustained-release tablets, capsules, granules, or powders.

[0085] In some embodiments, drug II contains an effective amount of traditional Chinese medicine composition I.

[0086] In some embodiments, the drug II comprises: (a) a traditional Chinese medicine composition I; and (b) pharmaceutically acceptable excipients and / or a pharmaceutically acceptable carrier. In some embodiments, the drug II comprises: a traditional Chinese medicine composition I and a pharmaceutically acceptable excipient. In some embodiments, the drug II comprises a traditional Chinese medicine composition I and a pharmaceutically acceptable carrier. In some embodiments, the drug II comprises a traditional Chinese medicine composition I, a pharmaceutically acceptable excipient, and a pharmaceutically acceptable carrier.

[0087] In some implementations, drug II is a blinding tablet.

[0088] Zhangyanming tablets are listed in the 2020 edition of the Chinese Pharmacopoeia and have the effects of tonifying the liver and kidneys, clearing away pterygium and improving vision. They are suitable for eye diseases such as dry eye, eye fatigue, and cataracts that cause vision loss.

[0089] In some embodiments, the mass percentage of the traditional Chinese medicine composition I in drug II is 85% to 90%, for example, 85%, 86%, 87%, 88%, 89%, 90%, etc.

[0090] In some implementations, the subjects of drug II are mammals.

[0091] In some implementations, the subjects of drug II are mice or humans.

[0092] In some implementations, drug II exerts a multi-target effect through multiple groups, intervening in the dominant flora in the gut, adjusting the gut microbiota structure, and improving gut microbiota imbalance.

[0093] See above for the definition of gut microbiota dysbiosis.

[0094] Second aspect of this application

[0095] A second aspect of this application provides a method for preventing and treating intestinal flora imbalance, comprising administering a therapeutically effective amount of a traditional Chinese medicine composition I to the patient. That is, administering a therapeutically effective amount of the traditional Chinese medicine composition I to the patient.

[0096] Application method

[0097] There are no particular restrictions on the dosage form and administration method of the blinding tablets (traditional Chinese medicine composition I) of this application.

[0098] Representative administration methods include, but are not limited to: oral, rectal, parenteral (intravenous, intramuscular or subcutaneous) injection, local administration, and inhalation.

[0099] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In these solid dosage forms, the active compound is mixed with at least one conventional inert excipient (or carrier), such as sodium citrate or dicalcium phosphate, or with the following components: (a) fillers or compatibilizers, such as starch, lactose, sucrose, glucose, mannitol, and silica; (b) binders, such as hydroxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose, and gum arabic; (c) humectants, such as glycerin; (d) disintegrants, such as agar, calcium carbonate, potato starch or cassava starch, alginate, certain complex silicates, and sodium carbonate; (e) slowing agents, such as paraffin; (f) absorption accelerators, such as quaternary ammonium compounds; (g) wetting agents, such as cetyl alcohol and glyceryl monostearate; (h) adsorbents, such as kaolin; and (i) lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium dodecyl sulfate, or mixtures thereof. In capsules, tablets, and pills, the dosage form may also contain a buffer. Solid dosage forms such as tablets, sugar pills, capsules, pills, and granules can be prepared using coatings and shells, such as casings and other materials known in the art. They may contain opacifying agents, and the release of the active compound or compound in such compositions may be delayed in a portion of the digestive tract. Examples of encapsulating components that may be used are polymeric substances and waxes. If necessary, the active compound may also be formed into microcapsules with one or more of the excipients described above.

[0100] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, or tinctures. In addition to the active compound, liquid dosage forms may contain inert diluents conventionally used in the art, such as water or other solvents, solubilizers, and emulsifiers, specifically, for example, ethanol, isopropanol, ethyl carbonate, ethyl acetate, propylene glycol, 1,3-butanediol, dimethylformamide, and oils, particularly cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil, and sesame oil, or mixtures thereof. Besides these inert diluents, the composition may also contain adjuvants such as wetting agents, emulsifiers and suspending agents, sweeteners, flavoring agents, and fragrances. For example, suspensions may contain suspending agents, specifically, for example, ethoxylated isooctadecyl alcohol, polyoxyethylene sorbitol and dehydrated sorbitan esters, microcrystalline cellulose, aluminum methoxide, and agar, or mixtures thereof.

[0101] Compositions for parenteral injection may comprise physiologically acceptable sterile aqueous or anhydrous solutions, dispersions, suspensions, or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions. Suitable aqueous or non-aqueous carriers, diluents, solvents, or excipients include water, ethanol, polyols, and suitable mixtures thereof.

[0102] Dosage forms for topical administration include ointments, powders, patches, sprays, and inhalers. They are prepared by mixing the active ingredient under sterile conditions with a pharmaceutically acceptable carrier and any preservatives, buffers, or propellants as needed.

[0103] It is understood that the drugs in the embodiments of this application can be prepared into suitable clinical dosage forms by adding different pharmaceutically acceptable excipients, including but not limited to the dosage forms described above. These pharmaceutically acceptable excipients include, but are not limited to, diluents, wetting agents, binders, disintegrants, lubricants, color and flavor modifiers, solvents, solubilizers, cosolvents, emulsifiers, antioxidants, metal complexing agents, inert gases, preservatives, local analgesics, pH adjusters, isotonic or isotropic regulators, etc. Furthermore: diluents, such as starch, sucrose, cellulose, inorganic salts, etc.; wetting agents, such as water, ethanol, etc.; binders, such as starch paste, dextrin, sugar, cellulose derivatives, gelatin, povidone, polyethylene glycol, etc.; disintegrants, such as starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, sodium bicarboxymethyl cellulose, crospovidone, surfactants, flaking disintegrants, etc.; lubricants, such as talc, calcium stearate, magnesium stearate, magnesium dodecyl sulfate, micronized silica gel, polyethylene glycol, etc.; color, flavor, and aroma modifiers, such as pigments, fragrances, sweeteners, etc. Flavoring agents, adhesives, and deodorants, such as fuchsin and xylitol; solvents, such as water, oil, ethanol, glycerin, propylene glycol, polyethylene glycol, dimethyl sulfoxide, liquid paraffin, fatty oils, and ethyl acetate; solubilizers, such as Tween compounds, maltose compounds, polyoxyethylene fatty alcohol ethers, soaps, sulfates, and sulfonates; cosolvents, such as organic acids (e.g., citric acid) and their salts, amides and amines, inorganic salts, polyethylene glycol, povidone-iodine, and glycerin; emulsifiers, such as Span compounds, Tween compounds, maltose compounds, benzyl esters, glyceryl fatty acid esters, and high-methylene glycol. Fatty acid salts, sulfates, sulfonates, gum arabic, tragacanth gum, gelatin, pectin, phospholipids, agar, sodium alginate, hydroxides, silica, bentonite, etc.; suspending agents, such as glycerin, syrup, gum arabic, tragacanth gum, agar, sodium alginate, cellulose derivatives, povidone, carboplatin, polyvinyl alcohol, thixotropic gum, etc.; antioxidants, such as sulfites, metabisulfites, bisulfites, ascorbic acid, gallic acid and its esters, etc.; metal complexing agents, such as disodium ethylenediaminetetraacetate, polycarboxylic acid compounds, etc.; inert gases, such as... Nitrogen, carbon dioxide, etc.; preservatives, such as parabens, organic acids and their salts (e.g., sodium benzoate), quaternary ammonium compounds, chlorhexidine acetate, alcohols, phenols, and volatile oils; local analgesics, such as benzyl alcohol, chlorobutanol, lidocaine, and procaine; pH adjusters, such as hydrochloric acid, sulfuric acid, phosphoric acid, tartaric acid, acetic acid, sodium hydroxide, sodium bicarbonate, ethylenediamine, meglumine, phosphates, acetates, citric acid, and citrates; isotonic or isotonic regulators, such as glucose, sodium chloride, sodium citrate, sorbitol, and xylitol.It is understood that the diluent described in the embodiments of this application can also be called a filler, and it plays the same role in pharmaceutical preparations; the water described in the embodiments of this application is water that meets the requirements of pharmaceutical preparations, such as water for injection, purified water, etc., and the oil is oil for injection; the preservative described in the embodiments of this application can also be called an antibacterial agent, and it plays a role in inhibiting microbial growth and extending shelf life in the preparation; the lubricant in the embodiments of this application contains flow aids, anti-adhesion agents, etc.; the sugar described in the embodiments of this application can be sugar powder or syrup, and the type of sugar is not limited to glucose; the fragrance described in the embodiments of this application includes, but is not limited to, flavorings.

[0104] In some implementations, the administration frequency is 1 to 3 times per day, for example, once per day, twice per day, or three times per day.

[0105] In some implementations, the dosage is 1.2 g / kg / day.

[0106] In some embodiments, the Chinese herbal composition I is administered orally.

[0107] In some embodiments, the traditional Chinese medicine composition I is administered by gavage.

[0108] In this article, "gavage" refers to the direct administration of liquids, suspensions, semi-liquids, etc., into the stomach via a catheter through the mouth or nose and esophagus. In some embodiments, the dosage is: 1.2 mL of physiological saline solution of the gavage drug composition I per kg of body weight (prepared by adding the traditional Chinese medicine composition I to physiological saline at a concentration of 1 g / mL, shaking, and dissolving at room temperature).

[0109] The “traditional Chinese medicine composition I” in the second aspect of this application may be selected from, but is not limited to, the traditional Chinese medicine composition I described above, and may be referred to the first aspect of this application.

[0110] In some embodiments, the traditional Chinese medicine composition I is a solid dosage form. In some of these embodiments, the solid dosage form is selected from ordinary tablets, dispersible tablets, sustained-release tablets, capsules, granules, or powders.

[0111] In some implementations, the patient is a human or a mouse.

[0112] In some implementations, the patient is a person.

[0113] In some implementations, the patient is a mouse.

[0114] Third aspect of this application

[0115] A third aspect of this application provides a traditional Chinese medicine composition I for preventing and treating intestinal flora imbalance.

[0116] The “traditional Chinese medicine composition I” in the third aspect of this application may be selected from, but is not limited to, the traditional Chinese medicine composition I described above, and may be referred to the first aspect of this application.

[0117] The following are some specific examples.

[0118] For experimental parameters not specified in the following specific embodiments, please refer to the guidelines given in this application document first, or refer to experimental manuals or other experimental methods known in the art, or refer to the experimental conditions recommended by the manufacturer.

[0119] The raw materials and reagents involved in the following specific embodiments can be obtained commercially or prepared by those skilled in the art using known methods.

[0120] The drug Zhangyanming tablets (National Drug Approval Number Z44022460) used in the following specific embodiments were provided by Guangzhou Baiyunshan Zhongyi Pharmaceutical Co., Ltd.

[0121] Example 1

[0122] 1. Experimental Methods

[0123] 1.1 Fifteen 6-8 week old C57BL / 6J mice were randomly divided into three groups: control group (NC group), model group (BCA group), and ZYMT intervention group (ZYMT group), with 5 mice in each group. Mice in the ZYMT group were given ZYMT at a dose of 1.2 g / kg body weight / day via gavage (ZYMT solution was 1 g / mL of ZYMT in physiological saline). Mice in the NC and BCA groups were given the same volume of physiological saline via gavage.

[0124] 1.2 Modeling Method: The following method was used for modeling in both the BCA and ZYMT groups.

[0125] (1) Prepare 0.2% benzalkonium chloride solution: Wrap the wall of a 15ml centrifuge tube with tin foil to protect it from light; weigh 0.03g of benzalkonium chloride powder into the 15ml centrifuge tube; add 15ml of sterile double-distilled water; after mixing, the 0.2% benzalkonium chloride solution (BCA) is prepared.

[0126] (2) Place the mouse on an iron frame, pull the mouse's tail back with your right hand, and gently lift the skin of the mouse's neck with your left hand to expose the eyes. Lift the mouse and use the ring finger and little finger of your left hand to hold the tail to completely control the mouse. At the same time, use a pipette to drop 5 μL of 0.2% benzalkonium chloride (BCA) into each eye, once in the morning and once in the evening for 14 days, to induce dry eye and intestinal flora imbalance. The control group mice were given 5 μL of sterile double-distilled water to drop into their eyes for 14 days in the same way.

[0127] 1.3 After the modeling and treatment intervention, mouse feces were collected for 16S rRNA gene sequencing to analyze the effect of Zhangyanming tablets on the intestinal microbiota of mice.

[0128] 2. Experimental Results

[0129] 2.1 Effects of Zhangyanming tablets on mouse intestinal flora

[0130] 2.1 PCA analysis of the effects of Zhangyanming tablets on the beta diversity of mouse gut microbiota

[0131] Beta diversity refers to the degree of diversity among organisms, i.e., comparing the differences between samples from different groups. Figure 1 PCA analysis results of gut microbiota beta diversity in mice from different groups (NC group, BCA group, ZYMT group) were used. Figure 1 It is evident that the differences between the BCA model group and the NC group are very significant, indicating that BCA administration significantly alters the gut microbiota diversity of the model mice. The difference between the ZYMT intervention group and the NC group is similar, suggesting that ZYMT administration can effectively regulate the gut microbiota of mice, improving it to near-normal levels.

[0132] 2.2 Effects of Zhangyanming tablets on the relative abundance of gut microbiota at the phylum level in mice

[0133] Cluster analysis was performed on the relative abundance of phyla in the gut microbiota of different groups of mice to obtain heatmaps as shown below. Figure 2 Bar chart as follows Figure 3 .according to Figure 2 and Figure 3 As can be seen, compared with the control group, the proportion of Bacteroidota and Verrucomicrobiota in the intestine of the BCA model group was significantly increased, while the proportion of Firmicutes was significantly decreased. Compared with the model group, after intervention with the cloning agent, the levels of Bacteroidota, Verrucomicrobiota and Firmicutes showed a significant correction, with the abundance of Bacteroidota and Verrucomicrobiota significantly decreasing and the abundance of Firmicutes significantly increasing, and the differences were statistically significant.

[0134] according to Figure 3 The F / B ratio was calculated from the data. The F / B ratio of the NC group was 0.605251681, the F / B ratio of the BCA group was 0.19124995, and the F / B ratio of the ZYMT group was 0.398555209. It can be seen that the F / B ratio of the BCA model group was significantly reduced. Compared with the model group, the F / B ratio was restored to near normal level after the intervention of the blind spot film.

[0135] 2.3 Effects of Zhangyanming tablets on the relative abundance of bacterial families in the intestinal flora of mice

[0136] Cluster analysis was performed on the relative abundance of gut microbiota at the family level in mice to obtain a heatmap, as shown below. Figure 4 Bar chart as follows Figure 5 .according to Figure 4 and Figure 5 It was observed that the relative abundance of Clostridia_vadinBB60 group and Ruminococcaceae in the BCA-induced intestinal flora dysbiosis model group was significantly decreased. After administration of Zhangyanming tablets, the levels of these three families showed a significant rebound, and the differences were statistically significant. Compared with the control group, the relative abundance of Muribaculaceae in the BCA-induced intestinal flora dysbiosis model group was significantly increased, while after administration of Zhangyanming tablets, the relative abundance of Muribaculaceae showed a significant decline, and the differences were statistically significant.

[0137] 2.4 Effects of Zhangyanming tablets on the relative abundance of genus bacteria in the intestinal flora of mice

[0138] Cluster analysis was performed on the relative abundance of bacterial genera in the mouse gut microbiota to obtain a heatmap, as shown below. Figure 6 Bar chart as follows Figure 7 .according to Figure 6 and Figure 7 It was observed that the relative abundance of *Muribaculum* in the BCA-induced gut microbiota dysbiosis model group was significantly increased; however, after administration of Zhangyanming tablets, the relative abundance of *Muribaculum* showed a significant decrease, and the difference was statistically significant. Compared with the control group, the relative abundance of *Eubacterium* xylanophilum group (p < 0.05) and *Oscillibacter* (p = 0.058) in the BCA-induced gut microbiota dysbiosis model group was significantly decreased, while after administration of Zhangyanming tablets, the relative abundance of *Eubacterium* xylanophilum group (p < 0.05) and *Oscillibacter* (p = 0.051) showed a significant rebound.

[0139] All references to this application are incorporated herein by reference as if each document were individually incorporated herein by reference. Unless they conflict with the purpose and / or technical solution of this application, all cited references are incorporated herein by reference in their entirety and for all purposes. When references are cited in this application, the definitions of relevant technical features, terms, nouns, phrases, etc., are also incorporated herein by reference. Examples and preferred embodiments of the cited technical features may also be incorporated herein by reference, but only to the extent that they enable the implementation of this application. It should be understood that when the cited content conflicts with the description in this application, this application shall prevail or modifications shall be made adaptably to the description in this application.

[0140] The technical features of the above-described embodiments and examples can be combined in any suitable manner. For the sake of brevity, not all possible combinations of the technical features in the above-described embodiments and examples are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0141] The embodiments described above merely illustrate several implementation methods of this application and should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Furthermore, it should be understood that after reading the above teachings, those skilled in the art can make various alterations or modifications to this application, and the equivalent forms obtained also fall within the protection scope of this application. It should also be understood that technical solutions obtained by those skilled in the art based on the technical solutions provided in this application through logical analysis, reasoning, or limited experimentation are all within the protection scope of the appended claims. Therefore, the protection scope of this patent application should be determined by the appended claims, and the specification can be used to interpret the content of the claims.

Claims

1. The application of Zhangyanming tablets in the preparation of drugs to improve intestinal flora imbalance, characterized in that, The aforementioned eye-brightening tablets are made from the following Chinese medicinal materials in parts by weight: 20-30 parts Acorus tatarinowii, 30-40 parts Cassia tora, 30-40 parts Cistanche deserticola, 30-40 parts Pueraria lobata, 30-40 parts Celosia argentea, 40-50 parts Codonopsis pilosula, 30-40 parts Vitex trifolia, 40-50 parts Lycium barbarum, 30-40 parts Plantago asiatica, 40-50 parts Paeonia lactiflora, 20-30 parts Cornus officinalis, 20-30 parts Glycyrrhiza uralensis, 60-70 parts Cuscuta chinensis, 1-10 parts Cimicifuga foetida, 30-40 parts Prunus armeniaca, 30-40 parts Chrysanthemum morifolium, 30-40 parts Buddleja officinalis, 30-40 parts Ligusticum chuanxiong, 30-40 parts Polygonatum sibiricum (processed with wine), 60-70 parts Rehmannia glutinosa (processed), 30-40 parts Phellodendron chinense, and 40-50 parts Astragalus membranaceus. The gut microbiota dysbiosis includes: increased relative abundance of Bacteroidetes and Verrucous microbes, decreased relative abundance of Firmicutes, decreased ratio between Firmicutes and Bacteroidetes, decreased relative abundance of Clostridium vadinBB60 and Rumenaceae, increased relative abundance of Muribacterium, increased relative abundance of Enterobacter spp., and decreased relative abundance of Xylanophilum spp. and Oscillatoria spp.

2. The application according to claim 1, characterized in that, The eye-brightening tablets are made from the following Chinese medicinal materials in parts by weight: 22 parts Acorus tatarinowii, 30 parts Cassia tora, 37 parts Cistanche deserticola, 37 parts Pueraria lobata, 30 parts Celosia argentea, 48 parts Codonopsis pilosula, 30 parts Vitex trifolia, 48 parts Lycium barbarum, 37 parts Plantago asiatica, 45 parts Paeonia lactiflora, 24 parts Cornus officinalis, 22 parts Glycyrrhiza uralensis, 61 parts Cuscuta chinensis, 7 parts Cimicifuga foetida, 37 parts Prunus armeniaca, 37 parts Chrysanthemum morifolium, 37 parts Buddleja officinalis, 30 parts Ligusticum chuanxiong, 37 parts Polygonatum sibiricum, 61 parts Rehmannia glutinosa, 30 parts Phellodendron chinense, and 48 parts Astragalus membranaceus.

3. The application according to claim 1 or 2, characterized in that, The intestinal flora imbalance was caused by benzalkonium chloride.

4. The application according to claim 1 or 2, characterized in that, The intestinal flora imbalance is caused by intestinal diseases, and the Zhangyanming tablets are used to prepare drugs for the prevention and treatment of the intestinal diseases.

5. The application according to claim 4, characterized in that, The intestinal diseases include at least one of megacolon, colitis, and constipation.

6. The application according to any one of claims 1, 2, and 5, characterized in that, The drug is a solid dosage form.

7. The application according to claim 6, characterized in that, The solid dosage form is a regular tablet, dispersible tablet, sustained-release tablet, capsule, granule, or powder.

8. The application according to any one of claims 1, 2, and 5, characterized in that, The drug contains an effective amount of the aforementioned eye-brightening tablets.

9. The application according to any one of claims 1, 2, and 5, characterized in that, The subjects of the drug are mammals.

10. The application according to claim 9, characterized in that, The subjects were mice or humans.

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