Traditional Chinese medicine composition, preparation method and application of traditional Chinese medicine composition in treatment of chronic alcoholic liver injury

Abstract

The invention relates to the technical field of medicine, in particular to a traditional Chinese medicine composition, a preparation method and application of the traditional Chinese medicine composition in treating chronic alcoholic liver injury, the traditional Chinese medicine composition takes lucid ganoderma and radix puerariae as monarch drugs, ginseng and poria cocos as ministerial drugs and walnut peptide as adjuvant and conductant drugs, and the five drugs are compatible, homologous in food and medicine, moderate in middle-level and mild, and harmonious in five internal organs; the effects of tonifying the spleen, soothing the liver, dispelling the effects of alcohol and eliminating evil are achieved. Experiments and clinical verifications prove that the traditional Chinese medicine composition can reduce the inflammation level of the liver by repairing intestinal mucosal barrier injury and reducing LPS entering blood and the liver, and has a good effect of preventing chronic alcoholic hepatitis. Moreover, the traditional Chinese medicine composition disclosed by the invention is simple to prepare, non-toxic and harmless, high in nutritional value and free of severe stimulation and harm to the body. The important social significance is realized on relieving liver inflammation and preventing and treating occurrence and development of liver diseases.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technologies, and particularly relates to a traditional Chinese medicine composition, a preparation method thereof, and a use for treating chronic alcoholic liver injury. Background Art

[0002] Alcoholic liver injury refers to a series of pathological changes such as liver damage caused by excessive alcohol intake. Alcoholic liver injury can be divided into acute alcoholic liver injury and chronic alcoholic liver injury. The occurrence and development of chronic alcoholic hepatitis are closely related to the impairment of the intestinal mechanical barrier, and the intestinal-liver axis is connected.

[0003] The TLR4 / MyD88 / NF-κB signaling pathway is an important pathway that triggers chronic alcoholic hepatitis. Due to the close connection between the intestine and the liver, which interact bidirectionally through the biliary tract, portal vein, and systemic circulation, the core of their communication is the function of the intestinal barrier. The continuous damage of alcohol to the intestinal mechanical barrier is a prerequisite for the occurrence of chronic alcoholic hepatitis. The key link of chronic alcoholic hepatitis is that intestinal endotoxin lipopolysaccharide (LPS) enters the liver through the blood after the intestinal mechanical barrier is damaged, causing long-term liver inflammation and inducing chronic alcoholic hepatitis.

[0004] Currently, the treatment plan for chronic alcoholic hepatitis in Western medicine is mainly to abstain from alcohol and cooperate with drug treatment. Clinical drugs mainly include corticosteroids, pentoxifylline, anti-tumor necrosis factor-alpha (TNF-α) preparations, and some antioxidants, etc., and there is no specific treatment drug. The curative effects of existing drugs are not ideal, and they can only improve symptoms in the short term and have many complications, with certain limitations.

[0005] The history of traditional Chinese medicine in treating alcoholic fatty liver is long, and as an important aspect of the comprehensive treatment of modern liver diseases, it has received increasing attention in recent years. Currently, traditional Chinese medicine has achieved certain curative effects in preventing and treating alcoholic fatty liver. Clinically, syndrome differentiation and treatment are emphasized, mainly using compound prescriptions, with syndrome differentiation and addition or subtraction, which can effectively improve symptoms. However, there is currently a lack of drugs for chronic alcoholic liver injury; therefore, in combination with the development theory of modern traditional Chinese medicine, starting from the perspective of improving drug curative effects and reducing side effects, preparations obtained by screening, extracting, and / or compatibility of traditional Chinese medicine ingredients have become a research focus and a scientific research difficulty. Summary of the Invention

[0006] In order to overcome the deficiencies of the above technical defects, the present invention gives full play to the advantages of traditional Chinese medicine health care, and provides a traditional Chinese medicine composition to regulate the functions of the spleen and stomach, realize the repair of the intestinal mechanical barrier and the transportation of alcohol, so as to intervene in chronic alcoholic hepatitis.

[0007] The inventor takes the gut-liver axis as the starting point, strengthens the spleen and thickens the intestine to relieve alcohol intoxication. The pathogenesis is the stagnation of earth qi and the depression of wood qi, disharmony between the liver and the spleen. The treatment principle is to harmonize the liver and the spleen, and the treatment method is "strengthening the spleen and soothing the liver, relieving alcohol intoxication and expelling pathogenic factors". Ganoderma lucidum, Pueraria lobata, Panax ginseng, Poria cocos, and walnut peptide are selected for reasonable compatibility, mainly to relieve alcohol pathogenic factors and benefit the liver and kidney, while strengthening the spleen and soothing the liver, and harmonizing the liver and the spleen.

[0008] One of the purposes of the present invention is to provide a traditional Chinese medicine composition, which is composed of the following raw materials: 3-10 parts by weight of Ganoderma lucidum, 6-15 parts by weight of Pueraria lobata, 6-15 parts by weight of Panax ginseng, 12-20 parts by weight of Poria cocos, and 110-440 mg / kg of oligomeric walnut peptide.

[0009] The present invention is based on the clinically effective prescription of a famous traditional Chinese medicine doctor in Yunnan Province for treating alcoholic liver disease. Through long-term practice, the curative effect is definite. This prescription is composed of five herbs: Ganoderma lucidum, Pueraria lobata, Panax ginseng, Poria cocos, and walnut peptide, which together play the role of "strengthening the spleen and soothing the liver, relieving alcohol intoxication and expelling pathogenic factors", and play a preventive role in chronic alcoholic hepatitis.

[0010] Among them, Ganoderma lucidum is sweet in taste and neutral in nature. It belongs to the liver, heart, spleen, lung, and kidney meridians, enters the five internal organs, tonifies the liver qi, and is the first herb for nourishing the liver, mainly nourishing the liver qi to soothe the liver and resolve alcohol. Pueraria lobata is sweet, pungent, and cool in nature. It belongs to the lung and stomach meridians. It dispels alcohol from the exterior and relieves alcohol intoxication, leads all herbs to benefit qi and promote the ascending of clear qi, generates fluid and quenches thirst to relieve symptoms such as dry mouth after drinking. The two herbs together serve as the monarch herbs;

[0011] Panax ginseng is sweet, slightly bitter, and slightly warm in nature. It belongs to the spleen and lung meridians. It tonifies the five internal organs, especially strengthens the qi in the middle jiao, enhances its dampness-dispelling function, and does not cause heat due to tonification. Poria cocos is sweet, light, and neutral in nature. It belongs to the heart, lung, spleen, and kidney meridians. It strengthens the spleen and promotes diuresis to eliminate dampness, leads the alcohol pathogenic factors to be dissipated from the lower jiao, restricts excessive tonification, so that there is elimination in tonification and no stagnation in tonification. The two herbs are combined to strengthen the spleen and remove dampness, assist the smooth flow of qi in the middle jiao, and disperse the alcohol nature, and together serve as the minister herbs;

[0012] Walnut kernels are sweet in taste and belong to the lung, kidney, and large intestine. They can tonify the liver and kidney, nourish and protect the liver, moisten the intestine to make the alcohol pathogenic factors be dissipated from the lower jiao, and expel pathogenic factors without harming the healthy qi, serving as the assistant herb. The five herbs are combined, with food and medicine sharing the same origin, being neutral and balanced, and regulating the five internal organs. Through the effect of "strengthening the spleen and soothing the liver, relieving alcohol intoxication and expelling pathogenic factors", it can effectively repair the intestinal mechanical barrier, thereby reducing the liver inflammation level and playing a preventive role in chronic alcoholic hepatitis.

[0013] In some specific embodiments, in the traditional Chinese medicine composition of the present invention, the amount of Ganoderma lucidum can be 3-10 parts by weight, or 3-10 parts by weight, or 5-10 parts by weight, or 3-6 parts by weight, or 6-9 parts by weight, or 6 parts by weight; and,

[0014] The amount of Pueraria lobata can be 6-15 parts by weight, or 6-12 parts by weight of Pueraria lobata, or 6-9 parts by weight of Pueraria lobata, or 9-15 parts by weight of Pueraria lobata, or 9-12 parts by weight of Pueraria lobata, or 9 parts by weight; and / or

[0015] The amount of ginseng can be 6 to 15 parts by weight, or 6 to 12 parts by weight of ginseng, or 6 to 9 parts by weight of ginseng, or 9 to 15 parts by weight of ginseng, or 9 to 12 parts by weight of ginseng, or 9 parts by weight; and / or

[0016] The amount of Poria cocos can be 12 to 20 parts by weight, or 15 to 20 parts by weight of Poria cocos, or 15 to 18 parts by weight of Poria cocos, or 12 to 18 parts by weight of Poria cocos, or 12 to 15 parts by weight of Poria cocos, or 15 parts by weight; and / or

[0017] The amount of oligomeric walnut peptide can be 110 to 440 mg / kg, or 110 to 380 mg / kg of oligomeric walnut peptide, or 110 to 350 mg / kg of oligomeric walnut peptide, or 150 to 300 mg / kg of oligomeric walnut peptide, or 200 to 250 mg / kg of oligomeric walnut peptide, or 220 mg / kg of oligomeric walnut peptide.

[0018] In some specific embodiments, the Ganoderma lucidum is one or a combination of Ganoderma lucidum powder and Ganoderma lucidum extract; and / or,

[0019] The Pueraria lobata is one or a combination of Pueraria lobata powder and Pueraria lobata extract; and / or,

[0020] The ginseng is one or a combination of ginseng powder and ginseng extract; and / or,

[0021] The Poria cocos is one or a combination of Poria cocos powder and Poria cocos extract.

[0022] The second object of the present invention is to provide a preparation method of the traditional Chinese medicine composition. Weigh the drug raw materials according to the formula, crush, decoct, and cool them; concentrate the obtained medicinal liquid until a viscous near-paste-like liquid is obtained, and then dry it to form an extract powder.

[0023] In some embodiments, the medicinal liquid is concentrated by a vacuum concentration method, and the concentration temperature is 40 to 42 °C, preferably 42 °C.

[0024] The third object of the present invention is to provide the application of the above traditional Chinese medicine composition and the traditional Chinese medicine composition prepared by the above preparation method in the preparation of drugs for preventing, alleviating or improving chronic alcoholic hepatitis. Preferably, the drug is a dosage form administered via the gastrointestinal tract.

[0025] The dosage form administered via the gastrointestinal tract refers to a dosage form in which a pharmaceutical preparation enters the gastrointestinal tract after oral administration and exerts a local or systemic effect through absorption, such as powders, tablets, granules, capsules, solutions, emulsions, and suspensions, etc.

[0026] The following applications are also within the protection scope of the present invention:

[0027] Furthermore, the mechanism of action of the drug is manifested as down-regulating the expression levels of the pathway proteins TLR4, MyD88, p-NF-κB, and NF-κB;

[0028] Furthermore, the mechanism of action of the drug is manifested as down-regulating the expression levels of the inflammatory factors TNF-α, IL-1β, and IL-6.

[0029] Furthermore, the dosage form administered via the gastrointestinal tract uses the composition as the active ingredient and is made with pharmaceutically acceptable excipients.

[0030] Furthermore, the amount of the active ingredient is 0.001 - 90 wt% relative to the total weight of the drug; or, 0.02 - 50 wt%; or 0.1 - 20%; or 0.005 - 5%.

[0031] In some specific embodiments, the amount of the active ingredient can be selected as 0.01%, 0.05%, 0.1%, 0.5%, 2%, 5%, 10%, 30%, 40%, 50%, 80% relative to the total weight of the drug;

[0032] Those skilled in the art are fully aware that the pharmaceutically acceptable carriers are generally recognized for this purpose and serve as the inactive ingredients of the medicament.

[0033] The excipients include solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, antiadhesives, chelating agents, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoaming agents, thickeners, clathrates, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, and release retardants.

[0034] Among them, the diluent can be one or more of mannitol, sucrose, lactose, sorbitol, xylitol, polyethylene glycol, propylene glycol, vegetable oil, and mineral oil; the disintegrant can be one or more of croscarmellose sodium, colloidal silicon dioxide, and citric acid; the binder can be one or more of starch paste, ethanol, water, and povidone alcohol solution; the preservative can be one or more of ethyl p-hydroxybenzoate, propyl hydroxybenzoate, sorbic acid, potassium sorbate, calcium propionate, sodium dehydroacetate, sodium diacetate, and sodium lactate; the antioxidant can be one or more of ethylenediaminetetraacetic acid, disodium ethylenediaminetetraacetate, dibutylhydroxytoluene, glycine, inositol, ascorbic acid, sodium ascorbate, lecithin, malic acid, hydroquinone, citric acid, succinic acid, and sodium metabisulfite; the flavoring agent can be one or more of aspartame, sucrose, xylitol, steviol glycosides, sodium cyclamate, sorbitol, cocoa, pure vanilla, vanillin, ethyl vanillin, chocolate, malt, and mint; the suspending agent can be one or more of xanthan gum, polyvinylpyrrolidone, sodium alginate, aluminum stearate, and hydrogenated vegetable oil; the emulsifier can be one or more of alkyl sulfates, soaps, dodecylbenzenesulfonates, lactate esters, sulfosuccinates, monoglyceride sulfonates, phosphate esters, siloxanes, and taurates.

[0035] In addition, if necessary, coloring agents, preservatives, fragrances, flavor correctives, sweeteners or other materials can also be added to the pharmaceutical preparation.

[0036] The dosage of the pharmaceutical composition of the present invention depends on many factors, such as the gender, age, weight and individual response of the patient or animal, the route of administration and the number of administrations, etc. The above dosage can be administered in a single dosage form or divided into several, for example, two, three or four dosage forms. The dosage level must be selected according to the specific route of administration, the severity of the condition to be treated and the condition and medical history of the patient to be treated, etc. However, the practice in the art is to start with a dosage lower than the level required to obtain the desired therapeutic effect and gradually increase the dosage until the desired effect is obtained.

[0037] It should be recognized, however, that the total daily dosage of the pharmaceutical composition of the present invention must be determined by the attending physician within the scope of sound medical judgment. For any particular patient, the specific therapeutically effective dosage level will depend on a variety of factors, including the disorder being treated and the severity of that disorder; the specific composition employed; the age, weight, general health, gender and diet of the patient; the time of administration, the route of administration and the excretion rate; the duration of treatment; the drugs used in combination with or concurrently with the composition; and like factors well known in the medical arts. For example, the practice in the art is to start with a dosage lower than the level required to obtain the desired therapeutic effect and gradually increase the dosage until the desired effect is obtained.

[0038] Generally speaking, the dosage of the pharmaceutical composition of the present invention calculated based on the active ingredient for mammals, especially humans, can range from 1 - 1000 mg / kg body weight per day, for example, from 1 - 500 mg / kg body weight per day, for example, from 50 - 500 mg / kg body weight per day, or 100 - 500 mg / kg, or 150 - 500 mg / kg, or 200 - 500 mg / kg, or 250 - 500 mg / kg.

[0039] In the traditional Chinese medicine composition of the present invention, Ganoderma lucidum and Pueraria lobata are used as the monarch drugs, Panax ginseng and Poria cocos are used as the minister drugs, and walnut peptide is used as the assistant and guiding drug. The five drugs are combined, with food and medicine sharing the same origin, being neutral and gentle, and regulating the five internal organs simultaneously, achieving the effect of "invigorating the spleen and soothing the liver, relieving alcoholism and dispelling pathogenic factors". Through experiments and clinical verification, it can repair the damage of the intestinal mucosal barrier, reduce the entry of LPS into the blood and liver, and lower the inflammatory level of the liver, having a good effect on preventing chronic alcoholic hepatitis. Moreover, the traditional Chinese medicine composition of the present invention is simple to prepare, non-toxic and harmless, with high nutritional value, and will not cause severe irritation and harm to the body. It has important social significance for alleviating liver inflammation and preventing and treating the occurrence and development of liver diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 It is the HE staining result diagram of the liver tissue of mice in the present invention;

[0041] Figure 2 It is the HE staining result diagram of the intestinal tissue of mice in the present invention;

[0042] Figure 3 It is the Oil Red O staining result diagram of the liver tissue of mice in the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0043] To enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be described in detail below in conjunction with the specific embodiments. The experimental methods without specific conditions noted in the following examples are usually carried out according to conventional conditions or according to the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are calculated by weight. Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to the described content can be applied to the present invention. The preferred implementation methods and materials described herein are for illustrative purposes only.

[0044] In the ranges disclosed herein, the endpoints and any values are not limited to the exact ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein.

[0045] Based on the present invention, the inventors believe that the injury of the spleen and stomach is the initiating factor of chronic alcoholic hepatitis. Based on traditional Chinese medicine theory, the spleen and stomach are the foundation of acquired constitution, responsible for transporting and transforming the essence of food and water, being the source of qi and blood generation and the pivot of the ascending and descending of zang-fu qi mechanism. The dredging function of the liver depends on the qi and blood nourishment and qi mechanism balance provided by the spleen and stomach. Modern medicine attributes the functions of the intestine to the spleen in the theory of zangxiang in traditional Chinese medicine. The spleen and stomach and the intestine are an integral whole, being interrelated and influencing each other. The function of the intestinal barrier to prevent the invasion of pathogenic antigens has the same academic connotation as the role of the spleen in preventing diseases and repelling pathogens described in the theory of "the spleen being the defender" in traditional Chinese medicine. The normal physiological functions of the intestine also depend on the nutrition, transportation and qi mechanism balance provided by the spleen and stomach. The intangible function of the spleen and stomach in transportation and transformation can be realized through the tangible intestinal mucosal barrier. Therefore, starting from the spleen and stomach and taking the intestine-liver axis as the entry point, strengthening the spleen and thickening the intestine to relieve alcoholism. Its pathogenesis is the stagnation of earth qi and the depression of wood qi, disharmony between the liver and the spleen. The treatment principle is to harmonize the liver and the spleen, and the treatment method is "strengthening the spleen and soothing the liver, relieving alcoholism and expelling pathogens". Five herbs, namely Ganoderma lucidum, Pueraria lobata, Panax ginseng, Poria cocos, and walnut oligopeptide, are selected to jointly achieve the effect of "strengthening the spleen and soothing the liver, relieving alcoholism and expelling pathogens", and play a preventive role in chronic alcoholic hepatitis.

[0046] According to the present invention, on the one hand, it relates to a pharmaceutical composition, which is composed of the following raw materials: 3-10 parts by weight of Ganoderma lucidum, 6-15 parts by weight of Pueraria lobata, 6-15 parts by weight of Panax ginseng, 12-20 parts by weight of Poria cocos, and 110-440 mg / kg of walnut oligopeptide.

[0047] In some embodiments, the Ganoderma lucidum is one or a combination of Ganoderma lucidum powder and Ganoderma lucidum extract; and / or,

[0048] The Pueraria lobata is one or a combination of Pueraria lobata powder and Pueraria lobata extract; and / or,

[0049] The Panax ginseng is one or a combination of Panax ginseng powder and Panax ginseng extract; and / or,

[0050] The Poria cocos is one or a combination of Poria cocos powder and Poria cocos extract.

[0051] In some embodiments, the traditional Chinese medicine composition is composed of Ganoderma lucidum powder, Pueraria lobata powder, Panax ginseng powder, Poria cocos powder, and walnut oligopeptide.

[0052] In some embodiments, the traditional Chinese medicine composition is composed of Ganoderma lucidum extract, Pueraria lobata extract, Panax ginseng extract, Poria cocos extract, and walnut oligopeptide.

[0053] In some embodiments, the traditional Chinese medicine composition is composed of Ganoderma lucidum extract, Pueraria lobata extract, Panax ginseng extract, Poria cocos extract, and walnut oligopeptide.

[0054] In some embodiments, the traditional Chinese medicine composition can be applied to patients with chronic alcoholic liver injury.

[0055] In some embodiments, in the composition of the present invention, the amount of Ganoderma lucidum can be 3 to 10 parts by weight, or 3 to 10 parts by weight, or 5 to 10 parts by weight, or 3 to 6 parts by weight, or 6 to 9 parts by weight, or 6 parts by weight.

[0056] In some embodiments, in the composition of the present invention, the amount of Pueraria lobata can be 6 to 15 parts by weight, or Pueraria lobata 6 to 12 parts by weight, or Pueraria lobata 6 to 9 parts by weight, or Pueraria lobata 9 to 15 parts by weight, or Pueraria lobata 9 to 12 parts by weight, or 9 parts by weight.

[0057] In some embodiments, in the composition of the present invention, the amount of Panax ginseng can be 6 to 15 parts by weight, or Panax ginseng 6 to 12 parts by weight, or Panax ginseng 6 to 9 parts by weight, or Panax ginseng 9 to 15 parts by weight, or Panax ginseng 9 to 12 parts by weight, or 9 parts by weight.

[0058] In some embodiments, in the composition of the present invention, the amount of Poria cocos can be 12 to 20 parts by weight, or Poria cocos 15 to 20 parts by weight, or Poria cocos 15 to 18 parts by weight, or Poria cocos 12 to 18 parts by weight, or Poria cocos 12 to 15 parts by weight, or 15 parts by weight; and

[0059] In some embodiments, in the traditional Chinese medicine composition of the present invention, the amount of oligomeric walnut peptides can be 110 to 440 mg / kg, or oligomeric walnut peptides 110 to 380 mg / kg, or oligomeric walnut peptides 110 to 350 mg / kg, or oligomeric walnut peptides 150 to 300 mg / kg, or oligomeric walnut peptides 200 to 250 mg / kg, or oligomeric walnut peptides 220 mg / kg.

[0060] In the present invention, the unit "mg / kg" refers to the amount of oligomeric walnut peptides added in mg per kg of the composition.

[0061] Those skilled in the art can understand that the "parts by weight" of each traditional Chinese medicine material represents the dosage ratio relationship between each traditional Chinese medicine material, rather than an actual mass unit. According to the actual situation, a unit part by weight can be any mass, such as 1 part by weight can be 1 g, 500 g or 1 kg, and even can be 15 g, 30 g, etc.

[0062] According to the present invention, on the other hand, it relates to a preparation method of the composition. Weigh the drug raw materials according to the formula, crush, decoct and cool them; concentrate the obtained medicinal liquid until a viscous near-paste-like liquid is obtained, and then dry it to form an extract powder.

[0063] In some embodiments, the medicinal liquid is concentrated by a vacuum concentration method, and the concentration temperature is 40 to 42 °C, preferably 42 °C.

[0064] In some embodiments, the vacuum concentration is carried out by a rotary evaporator for vacuum rotary evaporation.

[0065] On the other hand, the present invention relates to the use of the traditional Chinese medicine composition of the present invention for reducing chronic alcoholic liver injury.

[0066] On the other hand, the present invention relates to a method for reducing chronic alcoholic liver injury, which includes administering an effective amount of the traditional Chinese medicine composition of the present invention to a subject.

[0067] On the other hand, the present invention relates to the use of the traditional Chinese medicine composition of the present invention in the preparation of a drug, health product, or food for preventing, alleviating, or improving chronic alcoholic liver injury.

[0068] On the other hand, the present invention relates to a method for preventing, alleviating, or improving chronic alcoholic liver injury, which includes administering an effective amount of the traditional Chinese medicine composition of the present invention to a subject.

[0069] The traditional Chinese medicine composition of the present invention can be a gastrointestinal administration dosage form or a non-gastrointestinal administration dosage form, such as an oral dosage form.

[0070] A gastrointestinal administration dosage form refers to a dosage form in which a pharmaceutical preparation enters the gastrointestinal tract after oral administration and exerts a local or systemic effect through absorption, such as tablets, ointments, powders, decoctions, granules, capsules, or dripping pills, etc. In some embodiments, the traditional Chinese medicine composition, drug, health product, or food of the present invention is a capsule.

[0071] The dosage forms of the traditional Chinese medicine composition of the present invention according to the dispersion form include the following dosage forms:

[0072] Solution type: A uniform dispersion system formed by a drug in a molecular or ionic state (for example, the diameter of the particles is less than 1 nm) dispersed in a dispersion medium, also known as a low-molecular solution, such as aromatic waters, solutions, syrups, glycerins, spirits, injections, etc.

[0073] Colloidal solution type: A uniform dispersion system mainly formed by macromolecules (for example, the diameter of the particles is between 1 and 100 nm) dispersed in a dispersion medium, also known as a macromolecular solution, such as mucilage, collodion, film-forming agents, etc.

[0074] Emulsion type: A non-uniform dispersion system formed by an oily drug or a drug oil solution dispersed in a dispersion medium in the form of droplets, such as oral emulsions, intravenous emulsions, some liniments, etc.

[0075] Suspension type: A non-uniform dispersion system formed by a solid drug dispersed in a dispersion medium in the form of fine particles, such as mixtures, lotions, suspensions, etc.

[0076] Gas dispersion type: A dispersion system formed by a liquid or solid drug dispersed in a gas dispersion medium in the form of fine particles, such as aerosols.

[0077] Particle dispersion type: The drug is dispersed in a liquid or solid state in the form of particles of different sizes, such as microsphere preparations, microcapsule preparations, nanocapsule preparations, etc.

[0078] Solid dispersion type: A dispersion system in which solid drugs exist in an aggregated state, such as tablets, powders, granules, capsules, pills, etc.

[0079] The traditional Chinese medicine composition of the present invention may further include excipients, such as pharmaceutical excipients. The excipients (such as pharmaceutical excipients) may be selected from one or more of the following: solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, antiadhesives, chelating agents, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoaming agents, thickeners, clathrates, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, and release retardants.

[0080] The technical solution of the present invention will be further described in detail below in conjunction with specific embodiments and drawings. It should be understood that the following embodiments are only used to explain the present invention and are not used to limit the present invention.

[0081] Example 1

[0082] A traditional Chinese medicine composition is composed of the following parts by mass of drug raw materials: 6 parts of Ganoderma lucidum, 9 parts of Pueraria lobata, 9 parts of ginseng, 15 parts of Poria cocos, and 220 mg / kg of oligomeric walnut peptide.

[0083] The preparation method is as follows:

[0084] Weigh the drug raw materials (except walnut peptide) according to the above parts by mass, crush them, soak them in deionized water with a volume 10 - 15 times that of the drug raw materials for half an hour, bring to a boil over high heat, then switch to low heat and decoct for 30 minutes. After decocting, filter the medicinal residues with a gauze, pour the residues back into the pot and decoct again twice. When decocting for the second time, add deionized water with a volume 10 times that of the residues, bring to a boil over high heat, then switch to low heat and decoct for 30 minutes, and take the filtrate; for the third decoction, add deionized water with a volume 8 times that of the residues, bring to a boil over high heat, then switch to low heat and decoct for 30 minutes, filter and take the filtrate, and combine the filtrates obtained from the three decoctions to obtain a medicinal liquid, cool it to obtain a decoction. At the same time, dissolve the oligomeric walnut peptide at a dose of 220 mg / kg in the medicinal liquid to prepare a decoction.

[0085] The obtained decoction is further concentrated by using a rotary evaporator for vacuum rotary evaporation. The specific operation is as follows: Pour the cooled liquid into the rotary evaporation flask in multiple batches, and the liquid poured each time shall not exceed one-third of the total volume of the rotary evaporation flask. The rotary evaporation temperature is controlled at 42 °C, the rotation speed is adjusted to gear 4, the atmospheric pressure is first adjusted to 80 atmospheres, and the atmospheric pressure is reduced according to the situation after the rotary evaporation starts until it is concentrated into a viscous near-paste-like liquid. Pour the above-mentioned viscous near-paste-like liquid into a glassware and dry it in an oven until it becomes a paste, thus obtaining the paste preparation.

[0086] Example 2

[0087] The traditional Chinese medicine composition is composed of the following drug raw materials in parts by mass: 3 parts of Ganoderma lucidum, 15 parts of Pueraria lobata, 12 parts of Panax ginseng, 20 parts of Poria cocos, and 110 mg / kg of oligomeric walnut peptide.

[0088] The preparation method is the same as that of Example 1.

[0089] Example 3

[0090] The traditional Chinese medicine composition is composed of the following drug raw materials in parts by mass: 10 parts of Ganoderma lucidum, 6 parts of Pueraria lobata, 9 parts of Panax ginseng, 12 parts of Poria cocos, and 300 mg / kg of oligomeric walnut peptide.

[0091] The preparation method is the same as that of Example 1.

[0092] Example 4

[0093] The traditional Chinese medicine composition is composed of the following drug raw materials in parts by mass: 9 parts of Ganoderma lucidum, 15 parts of Pueraria lobata, 9 parts of Panax ginseng, 18 parts of Poria cocos, and 440 mg / kg of oligomeric walnut peptide.

[0094] The preparation method is as follows:

[0095] Weigh the drug raw materials (except walnut peptide) according to the above parts by mass, use 50% ethanol as the extraction solvent for percolation extraction. Before extraction, soak the drug raw materials with 1 - 3 times the volume of the solvent, and then use 8 - 9 times the volume of the solvent for extraction. The flow rate of percolation extraction is controlled at 4 - 5 ml / min. After the extraction is completed, obtain the extract. At the same time, dissolve the oligomeric walnut peptide at a dose of 220 mg / kg in the medicinal liquid to prepare a decoction;

[0096] Further subject the decoction to vacuum rotary evaporation by using a rotary evaporator to obtain a viscous near-paste-like liquid, and add excipients including fillers and lubricants to the above-mentioned viscous near-paste-like liquid, and then prepare it into tablets by wet granulation. Among them, the above-mentioned fillers and lubricants can be selected from the prior art.

[0097] Example 5

[0098] Traditional Chinese medicine composition, which is composed of the following drug raw materials in parts by mass: Ganoderma lucidum 5 parts, Pueraria lobata 12 parts, Panax ginseng 12 parts, Poria cocos 15 parts, oligomeric walnut peptide 150 mg / kg.

[0099] The preparation method is the same as that of Example 4.

[0100] Example 6

[0101] Traditional Chinese medicine composition, which is composed of the following drug raw materials in parts by mass: Ganoderma lucidum 9 parts, Pueraria lobata 15 parts, Panax ginseng 9 parts, Poria cocos 18 parts, oligomeric walnut peptide 250 mg / kg.

[0102] The preparation method is the same as that of Example 4.

[0103] The efficacy of the traditional Chinese medicine composition of the present invention was verified.

[0104] Experimental methods and materials: SPF-grade C57BL / 6NCr mice (male, body weight 20±2 g) were used as experimental materials and randomly divided into a blank group (NC), a model group (MOD), a low-dose group (LSG-L), a medium-dose group (LSG-M), and a high-dose group (LSG-H) according to experimental needs, with 5 mice in each group. A chronic alcoholic hepatitis model mouse was replicated by the method of chronic alcohol feeding plus acute alcohol gavage (NIAAA), and Lieber-DeCarli (LDC) liquid feed was fed. Before the experiment, the mice were adaptively fed with alcohol-free liquid feed for 5 days. During the formal experiment, the mice in the blank group were provided with alcohol-free isocaloric control liquid feed for 15 days, and the other groups were provided with liquid feed containing 5% alcohol for 15 days. Gavage administration started on the 6th day. On the 16th day, except for the blank group, a 31.5% (v / v) alcohol solution was gavage-administered at a dose of 5 g / kg at one time, and the blank group was gavage-administered with an equal volume and isocaloric maltodextrin solution. The experimental period was 16 days in total.

[0105] Low-dose group (LSG-L): The drug composition of Example 1 was administered at a dose of 3.12 g / kg per day.

[0106] Medium-dose group (LSG-M): The drug composition of Example 1 was administered at a dose of 6.24 g / kg per day.

[0107] High-dose group (LSG-H): The drug composition of Example 1 was administered at a dose of 12.48 g / kg / kg per day.

[0108] (1) Investigate the effect of administration on the histopathology of mice

[0109] Observation of histopathological changes under HE staining microscopy: After the tissue was taken, it was fixed with tissue fixative for 42 h. Then the dehydrated tissue was embedded in a paraffin embedding machine, and then the wax block was fixed on a microtome for sectioning. The sections were successively placed in a dewaxing solution, absolute ethanol, 75% alcohol, and deionized water for dewaxing. Hematoxylin staining was performed: The sections were successively immersed in hematoxylin staining solution, deionized water, differentiation solution, deionized water, and bluing solution, and then rinsed with running water. Eosin staining was performed: After sectioning, the sections were dehydrated with alcohol and immersed in eosin staining solution for staining. Subsequently, dehydration and mounting were carried out: The sections were successively immersed in absolute ethanol and xylene, and then mounted with neutral balsam, and the image information was collected. The experimental results of mouse liver and intestinal tissues are respectively as Figure 1-2 shown.

[0110] As Figure 1 shown, compared with the blank group, multiple hepatocytes in the model group of mice showed ballooning degeneration, and some Mallory bodies were visible; compared with the model group, after administration, the ballooning changes in the livers of mice in each dose group decreased, and the Mallory bodies decreased.

[0111] As Figure 2 shown, the colon tissue structure of the blank group of mice was complete, arranged orderly, with intact mucosal epithelium and a large number of goblet cells, without obvious edema and inflammatory infiltration; inflammatory cell infiltration and mucosal damage were visible in the colon tissue of the model group of mice; compared with the model group, after intervention, the inflammatory cell infiltration in the administration group decreased to varying degrees, and the mucosa was repaired.

[0112] Observation of histopathological changes by Oil Red O staining: Take out the fixed tissue and place it in 15% sucrose solution at 4°C for dehydration until it sinks to the bottom, then transfer it to 30% sucrose solution to repeat the dehydration process; gently blot the surface water of the dehydrated tissue with filter paper, place the tissue with the cut surface up on the embedding table, and appropriately drop OCT embedding medium around the tissue. Then quickly freeze it on the quick-freezing table, and section it after the OCT turns white and hardens; initially cut the embedded tissue to make the tissue surface flat, and then adjust the section thickness to 8 - 10 μm. Gently place a clean glass slide above the section to adsorb the tissue, then mark it and store it at -20°C for later use; take out the sections stored at -20°C and equilibrate them to room temperature, drop the fixing solution and let it stand for 15 minutes, rinse with running water and then air dry; mix the saturated Oil Red O staining solution and distilled water in a ratio of 6:4, heat it in a water bath at 60 - 70°C for 30 minutes, cool it to room temperature and filter it with filter paper, soak the sections in the Oil Red O working solution for 8 - 10 minutes; after the staining is completed, take out the sections and let them stay briefly for 3 seconds, then place them successively in 2 containers containing 60% isopropanol for differentiation, lasting for 3 seconds and 5 seconds respectively. Then, transfer the sections successively into 2 containers containing pure water for rinsing, 10 seconds each; immerse the sections in hematoxylin staining solution for re-staining for 3 - 5 minutes, then rinse them successively in 3 containers containing pure water for 5 seconds, 10 seconds and 30 seconds respectively. Use the differentiating solution for differentiation for 2 - 8 seconds, then rinse them in 2 containers containing distilled water for 10 seconds each, treat them with the blueing solution for 1 second, and finally gently rinse the sections in 2 containers containing tap water for 5 seconds and 10 seconds each. After completion, perform microscopic examination to evaluate the staining effect. The experimental results of mouse liver tissue are as Figure 3 shown.

[0113] In the pathological images, the cell nuclei are shown in blue, and the red ones are lipid droplets in the liver tissue.

[0114] As Figure 3 shown, compared with the blank group, obvious hepatic steatosis appeared in the livers of mice in the model group, and a large number of lipid droplets could be seen; compared with the model group, the hepatic steatosis of mice in each drug-administered group was alleviated.

[0115] It is indicated that the traditional Chinese medicine composition of the present invention can reduce ballooning degeneration of the liver in mice with chronic alcoholic hepatitis model, alleviate hepatic steatosis of mice with chronic alcoholic hepatitis model, and alleviate inflammatory infiltration and mucosal damage of the colon tissue of mice with chronic alcoholic hepatitis model.

[0116] (2) Investigate the effect of drug administration on the liver function of mice

[0117] After taking blood from the eyeballs, centrifuge at 2500 r for 15 minutes to obtain serum, and detect the changes in liver function indexes of mice in the serum. The ALT and AST in the mouse serum were detected by the microplate method. The method is as follows: Equilibrate the reagent kit (Jiancheng Bioengineering Research Institute, Nanjing, China) at room temperature for 20 min, and pre-warm the substrate solution at 37 °C for 20 min; Add 5 μL of the sample, 20 μL of reagent one to the assay wells, mix well by repeated pipetting, and react at 37 °C for 30 min. After the reaction is completed, add 20 μL of reagent two to the assay wells and the control wells respectively, add 5 μL of the sample to be tested to the control wells, mix well and continue to react for 20 min. Finally, add 200 μL of the prepared sodium hydroxide solution, let it stand at room temperature for 15 min, and measure the absorbance at a wavelength of 510 nm. Calculate the result by substituting it into the standard curve.

[0118] The experimental results are shown in Table 1 in the appendix.

[0119] Table 1

[0120]

[0121]

[0122] Note: Compared with the blank group (NC), # P < 0.05; compared with the model group (MOD), * P < 0.05.

[0123] ALT and AST belong to the escape enzymes released into the blood when hepatocytes are damaged, and are the most sensitive indicators reflecting hepatocyte damage. ALT exists in the cytoplasm of hepatocytes, and AST exists in the nuclei of hepatocytes. When alcohol abuse causes hepatocyte damage, ALT is released into the blood in large amounts, and the increase in AST mostly accompanies the increase in ALT, and the degree of its increase indicates the degree of hepatocyte damage.

[0124] As can be seen from the above table, in this study, the levels of serum ALT, AST, and AKP in each model group of alcoholic liver injury mice were significantly higher than those in the blank control group, indicating that the model was successfully established. As shown in the table, the contents of serum ALT and AST in the model group mice were significantly increased. After administration, the contents of serum ALT and AST in each administration group mice were significantly decreased, indicating that the pharmaceutical composition of the present invention can improve the liver function damage of alcoholic liver injury mice.

[0125] (3) Investigate the effect of administration on the serum lipid metabolism function of mice

[0126] Experimental conditions for supplementing TC, TG, LDL-C, and HDL-C:. The experimental results are shown in Table 2 in the appendix.

[0127] Table 2

[0128]

[0129]

[0130] Note: Compared with the blank group (NC), # P < 0.05; compared with the model group (MOD), * P < 0.05

[0131] As can be seen from the above table, compared with the blank group, the contents of TC, TG, and LDL-C in the serum of mice in the model group were significantly increased, while the content of HDL-C was significantly decreased, indicating that after drinking, the ethanol metabolite acetaldehyde binds forcibly to the proteins on the liver cell membrane to form acetaldehyde-protein adducts. The reduction of liver proteins will lead to the inability to transport the synthesized fat away, affecting the normal function of the liver. Excessive lipid deposition can activate the liver inflammatory response, leading to aggravated liver function damage; compared with the model group, the contents of TC, TG, and LDL-C in the serum of mice in each drug administration group were significantly decreased, and the content of HDL-C was significantly increased. It shows that the pharmaceutical composition of the present invention can reduce lipid deposition, regulate lipid metabolism disorders, and improve liver function damage in mice with alcoholic liver injury.

[0132] (3) Investigate the effects of drug administration on related proteins (ZO-1, Occludin, LPS, TLR4, MyD88, NF-κB) in mice

[0133] Protein immunoblotting was used to detect protein expression. Specifically: Weigh 0.04 - 0.06 g of colon tissue on ice and grind it thoroughly. Use a reagent to extract proteins, use the BCA protein assay method to detect protein content to determine the loading amount, prepare the gel, load the sample, perform electrophoresis, transfer the membrane, block for 1 h, then add the corresponding primary antibody and incubate overnight on a shaker at 4°C, wash the membrane, add the corresponding secondary antibody and incubate for 1 h, wash the membrane and then add ECL luminescent solution for imaging and photographing, and analyze the images. The detection results are shown in Table 3-5.

[0134] Table 3

[0135]

[0136]

[0137] Note: Compared with the blank group (NC), # P < 0.05; compared with the model group (MOD), * P < 0.05

[0138] One end of ZO-1 is connected to the proteins that make up the tight junction structure, while the other end is indirectly connected to the cytoskeleton in the cytoplasm, playing an important role in maintaining the integrity of the structure and function of tight junctions. When hepatic steatosis occurs, the expression of ZO-1 protein decreases, accompanied by intestinal barrier damage; Occludin has the functions of sealing the adjacent cell gaps, regulating the paracellular transport of substances, and regulating the aggregation of signal transduction molecules. Long-term heavy drinking can increase the blood ethanol concentration and reduce the expression of the tight junction protein Occludin in intestinal epithelial cells, increasing intestinal permeability and causing quantitative and qualitative changes in the intestinal flora.

[0139] As can be seen from the above table, compared with the blank group, the expression levels of the tight junction proteins ZO-1 and Occludin in the colon tissues of the model group mice decreased, indicating that alcohol dissolves the intestinal mucosal mucus and damages the intestinal epithelial cell barrier, resulting in increased intestinal permeability, infiltration of inflammatory cells in the colon, and damage to the intestinal mechanical barrier; after administration, the protein expression levels in each administration group showed an upward trend, indicating that the pharmaceutical composition can repair the damaged intestinal mucosa of the intestinal mechanical barrier and enhance the integrity of the intestinal mechanics.

[0140] Table 4

[0141]

[0142] Note: Compared with the blank group (NC), # P < 0.05; compared with the model group (MOD), * P < 0.05

[0143] After alcohol damages the intestinal mechanical barrier, the pathogenic factor LPS leaks through the damaged intestinal barrier for a long time, enters the blood circulation, reaches the liver through the portal vein, causes an inflammatory reaction, and induces liver tissue damage and intestinal mucosal barrier damage.

[0144] As can be seen from the above table, compared with the blank group, the LPS contents in the sera and liver tissues of the model group mice were significantly increased; compared with the model group, the LPS contents in the sera and liver tissues of each administration group mice were significantly decreased, indicating that the pharmaceutical composition can repair the intestinal mechanical barrier and improve the intestinal clearance ability of LPS.

[0145] Table 5

[0146]

[0147] Compared with the blank group (NC), # P < 0.05; compared with the model group (MOD), * P < 0.05

[0148] The intestinal-liver axis is associated with the TLR4 / MyD88 / NF-κB signaling pathway, which is an important pathway that triggers chronic alcoholic hepatitis. As can be seen from the above table, compared with the blank group, the protein expression levels of TLR4, MyD88, p-NF-κB, and NF-κB in the liver tissues of the model group mice increased, indicating that the intestinal barrier of the mice was damaged, LPS translocated into the blood, entered the liver through the portal vein, and specifically bound to the TLR4 receptor on hepatic macrophages. TLR4 recognized and transmitted signals to the intracellular protein MyD88, and then the inflammatory-related signaling pathway of nuclear transcription factor-κB (NF-κB) mediated by it was activated, which induced hepatocyte necrosis and promoted fatty degeneration and inflammatory reactions in the liver tissue. After administration, the protein expression levels of each administration group mice showed a downward trend.

[0149] (4) To investigate the effects of the administered drugs on inflammatory factors (TNF-α, IL-1β, IL-6, IL-10) in mice, 30 mg of liver and colon tissues of mice were taken respectively, homogenized on ice, and then centrifuged at 5000 g for 10 min at 4 °C to extract the supernatant. The mouse blood samples were placed at room temperature for 1 hour and then centrifuged at 3000 r / min for 10 minutes to obtain serum. An ELISA kit (Enzyme-linked Biotechnology Co., Ltd., Shanghai, China) was used to detect the expression levels of TNF-α, IL-1β, IL-6, and IL-10 in the supernatant and serum. The results are shown in Tables 6 - 8.

[0150] Table 6 Effects of the administered drugs on inflammatory factors in the liver tissues of mice

[0151]

[0152] Note: Compared with the blank group (NC), # P < 0.05; compared with the model group (MOD), * P < 0.05

[0153] Table 7 Effects of the administered drugs on inflammatory factors in the liver tissues of mice

[0154]

[0155] Table 8 Effects of the administered drugs on inflammatory factors in the serum of mice

[0156]

[0157] As can be seen from Tables 6 - 8, compared with the blank group, the contents of TNF-α, IL-1β, and IL-6 in the serum, liver, and colon tissues of the model group mice increased significantly, while the content of IL-10 decreased significantly; compared with the model group, the contents of TNF-α, IL-1β, and IL-6 in the serum, liver, and colon tissues of each administration group mice decreased significantly, while the content of IL-10 increased significantly.

[0158] The experimental results show that the traditional Chinese medicine composition of the present invention can repair the intestinal mucosal damage of the intestinal mechanical barrier, enhance the integrity of the intestinal mechanics, up-regulate the expression levels of tight junction proteins such as ZO-1 and Occludin, restore the intestinal barrier function, prevent LPS translocation, block its entry into the liver through the blood, and further regulate the TLR4 / MyD88 / NF-κB signaling pathway to reduce the content of pro-inflammatory factors and reduce the liver inflammatory response, thereby regulating the balance of the gut-liver axis and thus playing a preventive role in chronic alcoholic hepatitis.

[0159] Finally, it should be noted that the above description is only the preferred embodiment of the present invention. Those skilled in the art can make various similar representations under the inspiration of the present invention without violating the purpose and claims of the present invention, and such transformations all fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition, characterized in that, It consists of the following raw materials: 3 - 10 parts by weight of Ganoderma lucidum, 6 - 15 parts by weight of Pueraria lobata, 6 - 15 parts by weight of Panax ginseng, 12 - 20 parts by weight of Poria cocos, and 110 - 440 mg / kg of oligomeric walnut peptide.

2. The traditional Chinese medicine composition according to claim 1, wherein The raw material composition is: 3 - 10 parts by weight of Ganoderma lucidum, or 3 - 10 parts by weight, or 5 - 10 parts by weight, or 3 - 6 parts by weight, or 6 - 9 parts by weight, or 6 parts by weight; and / or 6 - 15 parts by weight of Pueraria lobata, or 6 - 12 parts by weight of Pueraria lobata, or 6 - 9 parts by weight of Pueraria lobata, or 9 - 15 parts by weight of Pueraria lobata, or 9 - 12 parts by weight of Pueraria lobata, or 9 parts by weight; and / or 6 - 15 parts by weight of Panax ginseng, or 6 - 12 parts by weight of Panax ginseng, or 6 - 9 parts by weight of Panax ginseng, or 9 - 15 parts by weight of Panax ginseng, or 9 - 12 parts by weight of Panax ginseng, or 9 parts by weight; and / or 12 - 20 parts by weight of Poria cocos, or 15 - 20 parts by weight of Poria cocos, or 15 - 18 parts by weight of Poria cocos, or 12 - 18 parts by weight of Poria cocos, or 12 - 15 parts by weight of Poria cocos, or 15 parts by weight; and / or 110 - 440 mg / kg of oligomeric walnut peptide, or 110 - 380 mg / kg of oligomeric walnut peptide, or 110 - 350 mg / kg of oligomeric walnut peptide, or 150 - 300 mg / kg of oligomeric walnut peptide, or 200 - 250 mg / kg of oligomeric walnut peptide, or 220 mg / kg of oligomeric walnut peptide.

3. The traditional Chinese medicine composition according to claim 1, wherein The Ganoderma lucidum is one or a combination of Ganoderma lucidum powder and Ganoderma lucidum extract; and / or The Pueraria lobata is one or a combination of Pueraria lobata powder and Pueraria lobata extract; and / or The Panax ginseng is one or a combination of Panax ginseng powder and Panax ginseng extract; and / or The Poria cocos is one or a combination of Poria cocos powder and Poria cocos extract.

4. The preparation method of the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, Take the pharmaceutical raw materials according to the formula amount, crush, decoct, and cool; concentrate the obtained medicinal liquid until a viscous near-paste-like liquid is obtained, and then dry it to form an extract powder.

5. The preparation method according to claim 3, characterized in that, The medicinal liquid is concentrated by a vacuum concentration method, and the concentration temperature is 40 - 42 °C.

6. Use of the traditional Chinese medicine composition according to any one of claims 1 - 3 and the traditional Chinese medicine composition prepared by the preparation method according to claim 5 or 6 in the preparation of a drug for preventing, alleviating or improving chronic alcoholic hepatitis.

7. The application according to claim 6, wherein The mechanism of action of the drug is shown as: a. Down-regulate the expression levels of the pathway proteins TLR4, MyD88, p-NF-κB, and NF-κB; b. Down-regulate the expression levels of the inflammatory factors TNF-α, IL-1β, and IL-6.

8. The application according to claim 6 or 7, characterized in that, The drug is a dosage form for gastrointestinal administration.

9. The application according to claim 8, characterized in that: The dosage form for gastrointestinal administration includes any one of tablets, ointments, powders, decoctions, granules, capsules or dripping pills.

10. The application according to claim 9, wherein: The dosage form for gastrointestinal administration is made with the composition as the active ingredient and pharmaceutically acceptable excipients.

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