A traditional Chinese medicine composition and drug for treating chronic gastritis

Abstract

This invention provides a traditional Chinese medicine composition and drug for treating chronic gastritis. The active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 5-45 parts of *Broussonetia papyrifera* leaf, 5-30 parts of *Smilax china*, 5-30 parts of *Pogostemon cablin*, 3-15 parts of *Coptis chinensis*, 5-30 parts of *Magnolia officinalis*, 5-45 parts of *Poria cocos*, 3-15 parts of *Amomum villosum*, 3-15 parts of *Pinellia ternata*, and 5-30 parts of *Citrus aurantium*. In the traditional Chinese medicine composition, *Broussonetia papyrifera* leaf and *Smilax china* together play the role of the principal drug, *Pogostemon cablin*, *Coptis chinensis*, and *Magnolia officinalis* are the assistant drugs, and *Poria cocos*, *Amomum villosum*, *Pinellia ternata*, and *Citrus aurantium* are the adjuvant drugs. The combined effects of these drugs are to dispel dampness and clear heat, regulate qi and harmonize the stomach, significantly improving the TCM syndrome and clinical symptoms of patients with chronic gastritis of the spleen and stomach damp-heat type, with no adverse reactions and good safety.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition and drug for treating chronic gastritis. Background Technology

[0002] Chronic gastritis refers to a chronic inflammatory reaction of the gastric mucosa caused by various factors. It is a common and frequently occurring disease in clinical practice. Its clinical symptoms are atypical, manifesting as nonspecific dyspeptic symptoms such as upper abdominal fullness or pain after eating, acid reflux, belching, and other discomfort, generally without a clear regularity. Physical examination may reveal mild tenderness or discomfort upon palpation of the upper abdomen. The symptoms of this disease are prone to recurrence, severely impacting the patient's quality of life. If the disease progresses for a long time, a few patients may experience systemic symptoms such as fatigue and weight loss. If intestinal metaplasia or intraepithelial neoplasia is also present, the risk of developing gastric cancer increases.

[0003] In recent years, with the accelerated pace of life and intensified social competition, people's mental stress has increased significantly, and their eating habits and lifestyles have also changed considerably, leading to a year-on-year increase in the incidence of chronic gastritis. Currently, the prevalence of chronic gastritis diagnosed endoscopically in my country is close to 90%. Chronic gastritis is closely related to genetic factors, work environment, emotional influence, and lifestyle. Current Western medicine treatment mainly focuses on symptomatic relief, often using antibiotics, proton pump inhibitors, antacids, colloidal bismuth preparations, and prokinetic drugs. Severe cases may also receive pain relief. However, problems such as recurrence after discontinuation of medication, drug side effects, and poor response in some patients exist.

[0004] Traditional Chinese medicine (TCM) has unique advantages and good efficacy in treating chronic gastritis. From a TCM perspective, this disease presents with various syndrome types, with spleen and stomach damp-heat syndrome being one of the most common. In recent years, due to improved living standards, excessive consumption of rich, fatty, and spicy foods has led to an increasing number of patients with spleen and stomach damp-heat syndrome. This is especially true in the Lingnan region, located in the subtropical zone near the South China Sea, where high temperatures and humidity prevail year-round, easily leading to damp-heat syndrome. Furthermore, the people of Lingnan tend to consume rich, fatty, and spicy foods and often indulge in cold drinks, further contributing to the accumulation of dampness and heat. Therefore, spleen and stomach damp-heat syndrome is common in the Lingnan region.

[0005] Traditional Chinese medicine (TCM) possesses unique advantages in treating chronic gastritis due to its syndrome differentiation and treatment principles. However, current treatments for chronic gastritis with spleen and stomach damp-heat syndrome are primarily based on empirical observations, and there is a significant lack of commercially available TCM preparations. Therefore, developing effective TCM preparations for treating chronic gastritis would meet the urgent medication needs of a large number of patients and greatly facilitate clinical use. Summary of the Invention

[0006] Based on this, the object of the present invention is to provide a traditional Chinese medicine composition and a medicine for treating chronic gastritis, and the traditional Chinese medicine composition can significantly improve the traditional Chinese medicine syndromes and clinical symptoms of patients with chronic gastritis of spleen and stomach damp-heat type, and there are no adverse reactions, and the safety is good.

[0007] To achieve the above object, the present invention adopts the following technical solutions.

[0008] In the first aspect of the present invention, there is provided a traditional Chinese medicine composition for treating chronic gastritis, and the active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 5-45 parts of Microcos paniculata leaves, 5-30 parts of Ilex rotunda, 5-30 parts of Pogostemon cablin, 3-15 parts of Coptis chinensis, 5-30 parts of Magnolia officinalis, 5-45 parts of Poria cocos, 3-15 parts of Amomum kravanh, 3-15 parts of Pinellia ternata processed with Rhizoma Zingiberis Recens, 5-30 parts of Aurantii Fructus Immaturus.

[0009] In some embodiments, the active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 5-30 parts of Microcos paniculata leaves, 5-20 parts of Ilex rotunda, 5-20 parts of Pogostemon cablin, 3-10 parts of Coptis chinensis, 5-20 parts of Magnolia officinalis, 5-30 parts of Poria cocos, 3-10 parts of Amomum kravanh, 3-10 parts of Pinellia ternata processed with Rhizoma Zingiberis Recens, 5-20 parts of Aurantii Fructus Immaturus.

[0010] In some preferred embodiments, the active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 10-20 parts of Microcos paniculata leaves, 5-15 parts of Ilex rotunda, 5-15 parts of Pogostemon cablin, 5-10 parts of Coptis chinensis, 5-15 parts of Magnolia officinalis, 10-20 parts of Poria cocos, 5-10 parts of Amomum kravanh, 5-10 parts of Pinellia ternata processed with Rhizoma Zingiberis Recens, 5-15 parts of Aurantii Fructus Immaturus.

[0011] More preferably, the active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 15 parts of Microcos paniculata leaves, 10 parts of Ilex rotunda, 10 parts of Pogostemon cablin, 5 parts of Coptis chinensis, 10 parts of Magnolia officinalis, 15 parts of Poria cocos, 5 parts of Amomum kravanh, 5 parts of Pinellia ternata processed with Rhizoma Zingiberis Recens, 10 parts of Aurantii Fructus Immaturus.

[0012] In the second aspect of the present invention, there is provided a preparation method of the traditional Chinese medicine composition as described above, and the preparation method includes the following steps: weighing raw materials according to the formula, adding an extraction solvent, extracting, and collecting the extract.

[0013] In some embodiments, the extraction includes decoction extraction, reflux extraction, maceration extraction, percolation extraction, distillation extraction, supercritical fluid extraction, ultrasonic extraction, microwave extraction.

[0014] In some embodiments, the extraction solvent is water or an organic solvent.

[0015] In some embodiments, the extraction is a decoction extraction, comprising the following steps: weighing the raw materials according to the formula, adding water and decocting 1 to 3 times; for the first decoction, adding 5 to 20 times the amount of water and decocting for 0.5 to 5 hours, collecting the volatile oil, and encapsulating it with 5 to 15 times the amount of beta-cyclodextrin to obtain a beta-cyclodextrin inclusion complex; filtering the decoction through an 80 to 200 mesh filter; adding 3 to 15 times the amount of water for the second and third decoctions respectively and decocting for 0.5 to 2 hours, and filtering the decoction through an 80 to 200 mesh filter; combining the filtrates, concentrating under reduced pressure at 60 to 70°C to obtain an extract with a relative density of 1.05 to 1.25, filtering through an 80 to 200 mesh filter, drying under vacuum at 60 to 70°C, and then adding the beta-cyclodextrin inclusion complex.

[0016] In some preferred embodiments, the preparation method includes the following steps: weighing the raw materials according to the formula, adding water and decocting twice; adding 10 times the amount of water and decocting for 2 hours in the first decoction, collecting the volatile oil, and encapsulating it with 8 times the amount of beta-cyclodextrin to obtain the beta-cyclodextrin inclusion complex for later use; filtering the decoction through a 100-mesh filter; adding 8 times the amount of water and decocting for 1 hour in the second decoction, and filtering the decoction through a 100-mesh filter; combining the filtrates, concentrating under reduced pressure at 60℃~70℃ to obtain an extract with a relative density of 1.10~1.15 (60℃), filtering through a 120-mesh filter, drying under vacuum at 60℃~70℃, and then adding the beta-cyclodextrin inclusion complex.

[0017] In a third aspect, the present invention provides the use of the traditional Chinese medicine composition as described above or the traditional Chinese medicine composition prepared by the preparation method as described above in the preparation of a medicament for treating chronic gastritis.

[0018] In a fourth aspect, the present invention provides a medicament for treating chronic gastritis, the medicament comprising the traditional Chinese medicine composition as described above or the traditional Chinese medicine composition prepared by the preparation method as described above, and a pharmaceutically acceptable carrier.

[0019] In some embodiments, the dosage form of the drug includes tablets, capsules, granules, pills, powders, syrups, creams, pills, oral liquids, tinctures, mixtures, lozenges, decoctions, medicated wines, teas, fluid extracts, and extracts.

[0020] In some embodiments, the method for preparing the drug includes the following steps: adding the pharmaceutically acceptable carrier to the traditional Chinese medicine composition, mixing, and preparing the drug.

[0021] This invention provides a traditional Chinese medicine composition, which is composed of the following herbs: *Broussonetia papyrifera* leaf, *Impatiens balsamina*, *Pogostemon cablin*, *Coptis chinensis*, *Magnolia officinalis*, *Poria cocos*, *Amomum villosum*, *Pinellia ternata*, and *Citrus aurantium*. *Broussonetia papyrifera* leaf is slightly acidic and cool in nature, and enters the spleen and stomach meridians, having the functions of promoting digestion, clearing heat, and eliminating dampness. *Impatiens balsamina* is bitter and cold in nature, and enters the lung, stomach, large intestine, and liver meridians, having the functions of clearing heat, detoxifying, eliminating dampness, and relieving pain. The combination of these two herbs can both eliminate dampness and clear heat, making them the principal herbs in the formula, working together to exert the effects of the chief herb. Patchouli is pungent and slightly warm, entering the spleen, stomach, and lung meridians. It can both aromatically disperse and dispel external dampness, preventing internal stagnation of Yang, and aromatically invigorate the spleen to resolve dampness, enabling the spleen to transport and transform water and prevent it from being trapped by dampness. Coptis chinensis is bitter and cold, entering the heart, spleen, stomach, liver, gallbladder, and large intestine meridians. It has the effects of clearing heat and drying dampness, purging fire and detoxifying. Magnolia officinalis is bitter, pungent, and warm, entering the spleen, stomach, lung, and large intestine meridians. It can regulate Qi, resolve dampness, dry dampness, and relieve fullness. These three herbs together serve as assistant herbs. Poria cocos is mildly diuretic and promotes diuresis, clearing the water passages; Amomum villosum resolves dampness, promotes Qi circulation, warms the middle Jiao, stops vomiting, invigorates the spleen, and opens the stomach; Pinellia ternata dries dampness and harmonizes the middle Jiao; Citrus aurantium regulates Qi, relieves fullness, and eliminates stagnation and distension. These are all adjuvant herbs. Together, these herbs work to dispel dampness, clear heat, regulate Qi, and harmonize the stomach.

[0022] The traditional Chinese medicine composition of this invention can significantly improve the TCM syndrome and clinical symptoms of patients with chronic gastritis of the spleen and stomach damp-heat type, and has no adverse reactions and good safety. Attached Figure Description

[0023] Figure 1 This shows the frequency distribution of patients' clinical symptoms before treatment.

[0024] Figure 2 The results of gastric mucosal histopathological examination of rats with chronic gastritis in each group are shown.

[0025] Figure 3 The results of detecting the expression levels of TNF-α, IL-1β, and IL-10 in the serum of rats in each group ( n=6); Compared with the Control group, ***P<0.001; Compared with the Model group ## P < 0.01, ### P < 0.001.

[0026] Figure 4 The results of pepsin activity detection in the gastric tissue of rats in each group ( n=6); Compared with the Control group, ***P<0.001; Compared with the Model group ## P < 0.01, ### P < 0.001. Detailed Implementation

[0027] Unless otherwise specified, the experimental methods described in the following embodiments of the present invention are generally performed under conventional conditions or as recommended by the manufacturer. All commonly used chemical reagents used in the embodiments are commercially available products.

[0028] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to limit the invention.

[0029] The terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion. For example, a process, method, apparatus, product, or device that includes a series of steps is not limited to the steps or modules listed, but may optionally include steps not listed, or may optionally include other steps inherent to such process, method, product, or device.

[0030] The traditional Chinese medicine composition of this invention uses *Bletilla striata* leaf, *Smilax china*, *Pogostemon cablin*, *Coptis chinensis*, *Magnolia officinalis*, *Poria cocos*, *Amomum villosum*, *Pinellia ternata*, and *Citrus aurantium* to form a compound formula, which has a good therapeutic effect on chronic gastritis diagnosed as spleen and stomach damp-heat syndrome in traditional Chinese medicine. Previous basic and clinical studies have shown that this medicine has good efficacy and no adverse reactions have been observed, demonstrating significant advantages.

[0031] In the traditional Chinese medicine composition of this invention, *Buzhaye* leaf is slightly acidic and cool in nature, and enters the spleen and stomach meridians. According to *Ben Cao Qiu Yuan*, it can "relieve all kinds of bloating and poisoning, clear heat, eliminate food stagnation, and treat jaundice," thus having the effects of promoting digestion, clearing heat, and promoting diuresis. *Jiu Biying* is bitter and cold in nature, and enters the lung, stomach, large intestine, and liver meridians. According to *Lingnan Caiyao Lu*, it can "clear heat and toxins," and *Jiangxi Caoyao Shouce* records that it can "clear heat and promote diuresis, reduce swelling and relieve pain," thus having the effects of clearing heat and detoxifying, promoting diuresis and relieving pain. The two herbs combined can both remove dampness and clear heat, and are the main herbs in the formula, working together to exert the effects of the principal herbs. Patchouli is pungent and slightly warm, entering the spleen, stomach, and lung meridians. It can both aromatically disperse and dispel external dampness, preventing internal stagnation of Yang, and aromatically invigorate the spleen to resolve dampness, enabling the spleen to transport and transform water and prevent it from being trapped by dampness. Coptis chinensis is bitter and cold, entering the heart, spleen, stomach, liver, gallbladder, and large intestine meridians. It has the effects of clearing heat and drying dampness, purging fire and detoxifying. Magnolia officinalis is bitter, pungent, and warm, entering the spleen, stomach, lung, and large intestine meridians. It can regulate Qi, resolve dampness, dry dampness, and relieve fullness. These three herbs together serve as assistant herbs. Poria cocos is mildly diuretic and promotes diuresis, clearing the water passages; Amomum villosum resolves dampness, promotes Qi circulation, warms the middle Jiao, stops vomiting, invigorates the spleen, and opens the stomach; Pinellia ternata dries dampness and harmonizes the middle Jiao; Citrus aurantium regulates Qi, relieves fullness, and eliminates stagnation and distension. These are all adjuvant herbs. Together, these herbs work to dispel dampness, clear heat, regulate Qi, and harmonize the stomach.

[0032] The traditional Chinese medicine composition of this invention can be prepared into a drug together with a pharmaceutically acceptable carrier. The raw material slices are weighed according to the specified ratio to obtain the traditional Chinese medicine composition slices. The traditional Chinese medicine composition slices are then extracted to obtain the active ingredient. A pharmaceutically acceptable carrier is added to the active ingredient, and the corresponding drug is prepared according to conventional techniques in the art.

[0033] The drug can be any oral form, including but not limited to tablets, capsules, granules, pills, powders, syrups, creams, pills, oral liquids, tinctures, mixtures, lozenges, decoctions, medicated wines, teas, fluid extracts, and extracts; preferably granules.

[0034] The traditional Chinese medicine composition of the present invention is preferably in the form of a unit dose pharmaceutical preparation.

[0035] The traditional Chinese medicine composition of the present invention, when prepared into a pharmaceutical preparation, may contain 0.1-1000 mg of the active pharmaceutical ingredient of the traditional Chinese medicine composition per unit dose, with the remainder being a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may be 0.01-99.99% by weight of the total weight of the preparation.

[0036] When using the composition of the present invention, the dosage and administration method shall be determined according to the patient's condition, such as 1-3 times a day, 1-10 tablets each time, etc.

[0037] The pharmaceutical preparations of the present invention, when administered orally, may contain commonly used excipients, such as binders, fillers, diluents, tableting agents, lubricants, disintegrants, colorants, flavoring agents, and humectants, and the tablets may be coated if necessary.

[0038] Suitable fillers include cellulose, mannitol, lactose, and other similar fillers. Suitable disintegrants include starch, polyvinylpyrrolidone, and starch derivatives, such as sodium glycolate starch. Suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulfate.

[0039] The traditional Chinese medicine composition of the present invention can be prepared into solid oral dosage forms using common methods such as mixing, filling, and tableting. Repeated mixing allows the active substances to be distributed throughout those dosage forms that use a large amount of filler.

[0040] Oral liquid formulations may take the form of aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs, or may be a dry product that can be reconstituted with water or other suitable carriers before use. Such liquid formulations may contain conventional additives, such as suspending agents like sorbitol, syrups, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel, or hydrogenated edible fats; emulsifiers like lecithin, dehydrated sorbitan monooleate, or gum arabic; non-aqueous carriers (which may include edible oils such as almond oil, fractionated coconut oil, oily esters such as glycerol, propylene glycol, or ethanol); preservatives such as methylparaben or propylparaben or sorbic acid; and, if desired, conventional flavorings or colorings.

[0041] The traditional Chinese medicine composition of the present invention may optionally be added with suitable pharmaceutically acceptable carriers when being prepared into drugs. The pharmaceutically acceptable carriers include, but are not limited to, mannitol, sorbitol, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, cysteine hydrochloride, mercaptoacetic acid, methionine, vitamin C, disodium EDTA, calcium disodium EDTA, carbonates, acetates, phosphates of monovalent alkali metals or their aqueous solutions, 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, alginates, gelatin, polyvinylpyrrolidone, glycerol, polysorbate 80, agar, calcium carbonate, calcium bicarbonate, surfactants, polyethylene glycol, cyclodextrin, β - cyclodextrin, phospholipid materials, kaolin, talcum powder, calcium stearate, magnesium stearate, etc.

[0042] The following will be described in conjunction with specific examples.

[0043] Example 1

[0044] This example provides a traditional Chinese medicine composition for treating chronic gastritis. The active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 15 parts of Microcos paniculata leaves, 10 parts of Ilex rotunda, 10 parts of Pogostemon cablin, 5 parts of Coptis chinensis, 10 parts of Magnolia officinalis, 15 parts of Poria cocos, 5 parts of Amomum kravanh, 5 parts of Pinellia ternata, and 10 parts of Aurantii Fructus Immaturus.

[0045] The preparation method of the traditional Chinese medicine composition includes the following steps: Weigh Microcos paniculata leaves, Ilex rotunda, Pogostemon cablin, Coptis chinensis, Magnolia officinalis, Poria cocos, Amomum kravanh, Pinellia ternata, and Aurantii Fructus Immaturus according to the formula, and decoct twice with water. For the first time, add 10 times the amount of water and decoct for 2 hours, collect the volatile oil, and include it with 8 times the amount of beta - cyclodextrin to obtain a beta - cyclodextrin inclusion complex for standby; filter the decoction liquid through a 100 - mesh sieve. For the second time, add 8 times the amount of water and decoct for 1 hour, and filter the decoction liquid through a 100 - mesh sieve. Combine the filtrates, concentrate under reduced pressure at 65°C to obtain an extract with a relative density of 1.1 (60°C), filter through a 120 - mesh sieve, vacuum - dry at 65°C, then add the beta - cyclodextrin inclusion complex, pulverize, add appropriate excipients, mix evenly, and prepare into a granule drug according to the conventional preparation method.

[0046] Example 2

[0047] This example provides a traditional Chinese medicine composition for treating chronic gastritis. The active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 30 parts of Microcos paniculata leaves, 25 parts of Ilex rotunda, 15 parts of Pogostemon cablin, 10 parts of Coptis chinensis, 15 parts of Magnolia officinalis, 30 parts of Poria cocos, 15 parts of Amomum kravanh, 10 parts of Pinellia ternata, and 15 parts of Aurantii Fructus Immaturus.

[0048] The preparation method of the traditional Chinese medicine composition comprises the following steps: Weigh Microcos paniculata L., Ilex rotunda Thunb., Pogostemon cablin (Blanco) Benth., Coptis chinensis Franch., Magnolia officinalis Rehd. et Wils., Poria cocos (Schw.) Wolf., Amomum kravanh Pierre ex Gagnep., Pinellia ternata (Thunb.) Breit. and Aurantii Fructus Immaturus according to the formula, and decoct with water three times. For the first time, add 15 times the amount of water and decoct for 3 hours, collect the volatile oil, and include it with 10 times the amount of beta-cyclodextrin to obtain the beta-cyclodextrin inclusion compound for standby; filter the decoction liquid through a 100-mesh sieve. For the second time, add 10 times the amount of water and decoct for 1 hour, and filter the decoction liquid through a 100-mesh sieve. For the third time, add 10 times the amount of water and decoct for 1 hour, and filter the decoction liquid through a 100-mesh sieve. Combine the filtrates, concentrate under reduced pressure at 60 °C to obtain an extract with a relative density of 1.2 (60 °C), filter through a 120-mesh sieve, dry under vacuum at 68 °C, then add the above-mentioned beta-cyclodextrin inclusion compound, pulverize, add an appropriate amount of auxiliary materials, mix evenly, and prepare into tablets according to the conventional preparation method of preparations.

[0049] Example 3

[0050] This example provides a traditional Chinese medicine composition for treating chronic gastritis. The active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 45 parts of Microcos paniculata L., 15 parts of Ilex rotunda Thunb., 25 parts of Pogostemon cablin (Blanco) Benth., 15 parts of Coptis chinensis Franch., 25 parts of Magnolia officinalis Rehd. et Wils., 45 parts of Poria cocos (Schw.) Wolf., 10 parts of Amomum kravanh Pierre ex Gagnep., 15 parts of Pinellia ternata (Thunb.) Breit., and 25 parts of Aurantii Fructus Immaturus.

[0051] The preparation method of the traditional Chinese medicine composition comprises the following steps: Weigh Microcos paniculata L., Ilex rotunda Thunb., Pogostemon cablin (Blanco) Benth., Coptis chinensis Franch., Magnolia officinalis Rehd. et Wils., Poria cocos (Schw.) Wolf., Amomum kravanh Pierre ex Gagnep., Pinellia ternata (Thunb.) Breit. and Aurantii Fructus Immaturus according to the formula, and decoct with water twice. For the first time, add 5 times the amount of water and decoct for 1 hour, collect the volatile oil, and include it with 5 times the amount of beta-cyclodextrin to obtain the beta-cyclodextrin inclusion compound for standby; filter the decoction liquid through a 100-mesh sieve. For the second time, add 15 times the amount of water and decoct for 2 hours, and filter the decoction liquid through a 100-mesh sieve. Combine the filtrates, concentrate under reduced pressure at 70 °C to obtain an extract with a relative density of 1.25 (60 °C), filter through a 120-mesh sieve, dry under vacuum at 70 °C, then add the above-mentioned beta-cyclodextrin inclusion compound, pulverize, add an appropriate amount of auxiliary materials, mix evenly, and prepare into capsules according to the conventional preparation method of preparations.

[0052] Example 4

[0053] This example provides a traditional Chinese medicine composition for treating chronic gastritis. The active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 10 parts of Microcos paniculata L., 10 parts of Ilex rotunda Thunb., 5 parts of Pogostemon cablin (Blanco) Benth., 4 parts of Coptis chinensis Franch., 6 parts of Magnolia officinalis Rehd. et Wils., 10 parts of Poria cocos (Schw.) Wolf., 4 parts of Amomum kravanh Pierre ex Gagnep., 3 parts of Pinellia ternata (Thunb.) Breit., and 8 parts of Aurantii Fructus Immaturus.

[0054] The preparation method of the traditional Chinese medicine composition comprises the following steps: Weigh leaves of Microcos paniculata, bark of Ironwood Tree, Pogostemon cablin, Coptis chinensis, Magnolia officinalis, Poria cocos, Amomum kravanh, Pinellia ternata processed with Rhizoma Zingiberis Recens and Fructus Aurantii Immaturus according to the formula, and decoct with water three times. For the first time, add 10 times the amount of water and decoct for 2 hours, collect the volatile oil, and include it with 12 times the amount of beta-cyclodextrin to obtain a beta-cyclodextrin inclusion compound for standby; filter the decoction liquid through a 100-mesh sieve. For the second time, add 5 times the amount of water and decoct for 0.5 hour, and filter the decoction liquid through a 100-mesh sieve. For the third time, add 5 times the amount of water and decoct for 0.5 hour, and filter the decoction liquid through a 100-mesh sieve. Combine the filtrates, concentrate under reduced pressure at 62 °C to obtain an extract with a relative density of 1.05 (60 °C), filter through a 120-mesh sieve, add the above-mentioned beta-cyclodextrin inclusion compound after vacuum drying at 60 °C, pulverize, then add appropriate excipients, mix evenly, and prepare into pills according to the conventional preparation method of preparations.

[0055] Example 5

[0056] This example provides a traditional Chinese medicine composition for treating chronic gastritis. The active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 8 parts of leaves of Microcos paniculata, 5 parts of bark of Ironwood Tree, 6 parts of Pogostemon cablin, 3 parts of Coptis chinensis, 5 parts of Magnolia officinalis, 8 parts of Poria cocos, 3 parts of Amomum kravanh, 4 parts of Pinellia ternata processed with Rhizoma Zingiberis Recens, and 5 parts of Fructus Aurantii Immaturus.

[0057] The preparation method of the traditional Chinese medicine composition comprises the following steps: Weigh leaves of Microcos paniculata, bark of Ironwood Tree, Pogostemon cablin, Coptis chinensis, Magnolia officinalis, Poria cocos, Amomum kravanh, Pinellia ternata processed with Rhizoma Zingiberis Recens and Fructus Aurantii Immaturus according to the formula, and decoct with water twice. For the first time, add 20 times the amount of water and decoct for 4 hours, collect the volatile oil, and include it with 10 times the amount of beta-cyclodextrin to obtain a beta-cyclodextrin inclusion compound for standby; filter the decoction liquid through a 100-mesh sieve. For the second time, add 10 times the amount of water and decoct for 1.5 hours, and filter the decoction liquid through a 100-mesh sieve. Combine the filtrates, concentrate under reduced pressure at 62 °C to obtain an extract with a relative density of 1.2 (60 °C), filter through a 120-mesh sieve, add the above-mentioned beta-cyclodextrin inclusion compound after vacuum drying at 65 °C, pulverize, then add appropriate excipients, mix evenly, and prepare into syrup according to the conventional preparation method of preparations.

[0058] Example 6

[0059] This example is the clinical study of the drug of the present invention for treating chronic gastritis.

[0060] 1. Research object

[0061] 1.1 Case source

[0062] Collect patients who visited the outpatient department of Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2018 to July 2022 and were diagnosed with chronic gastritis and belonged to the syndrome of dampness-heat in spleen and stomach according to traditional Chinese medicine syndrome differentiation.

[0063] 1.2 Diagnostic criteria

[0064] 1.2.1 Western medicine diagnostic criteria

[0065] Referring to the diagnostic criteria of the "Consensus Opinion on Chronic Gastritis in China" (Shanghai, 2017), the "Consensus Opinion on the Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Chronic Non-Atrophic Gastritis" (2017), and the "Consensus Opinion on the Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Chronic Atrophic Gastritis" (2017), the diagnosis of chronic gastritis mainly relies on endoscopic and pathological histological examination results. Based on these, it can be diagnosed into two basic types: chronic non-atrophic gastritis and chronic atrophic gastritis. Endoscopic examination allows direct visualization of mucosal color, texture, submucosal blood vessels, fold morphology, and the presence of inflammatory or erosive changes such as congestion, edema, and damage. Pathological diagnosis includes five histological changes and four grades. When dysplasia is present, it is also classified as mild, moderate, and severe, or described as low-grade / high-grade intraepithelial neoplasia. See Table 1 for details.

[0066] Table 1. Pathological diagnostic criteria for chronic gastritis

[0067]

[0068]

[0069] 1.2.2 Traditional Chinese Medicine Diagnostic Criteria

[0070] This was formulated with reference to the "Expert Consensus Opinion on the Diagnosis and Treatment of Chronic Gastritis with Traditional Chinese Medicine" (2017), the "Consensus Opinion on the Diagnosis and Treatment of Chronic Non-Atrophic Gastritis with Integrated Traditional Chinese and Western Medicine" (2017), and the "Consensus Opinion on the Diagnosis and Treatment of Chronic Atrophic Gastritis with Integrated Traditional Chinese and Western Medicine" (2017), as well as the diagnostic criteria for damp-heat syndrome of the spleen and stomach, and in combination with clinical practice.

[0071] Main symptom: abdominal distension or pain.

[0072] Secondary symptoms: ① poor appetite; ② bitter taste in the mouth and bad breath; ③ heaviness and fatigue in the body; ④ sticky or loose stools.

[0073] Tongue and pulse: The tongue is red with a yellow, greasy coating; the pulse is slippery or rapid.

[0074] Diagnosis based on syndrome differentiation: The patient presents with two symptoms, including the primary symptom and two secondary symptoms, and the diagnosis is made with reference to the tongue and pulse.

[0075] 1.2.3 Quantitative Standards for Symptom Grading in Traditional Chinese Medicine

[0076] Based on the above expert consensus and the "Traditional Chinese Medicine Symptom Scoring Table for Gastrointestinal Diseases" (2010), a quantitative scoring table for TCM symptom grading is proposed, as detailed in Table 2.

[0077] Table 2 Quantitative Standards for Symptom Grading in Traditional Chinese Medicine

[0078]

[0079]

[0080] 1.2.4 Inclusion Criteria

[0081] (1) Meets the Western medicine diagnostic criteria for chronic gastritis;

[0082] (2) It meets the diagnostic criteria for damp-heat syndrome of spleen and stomach in traditional Chinese medicine;

[0083] (3) Age between 18 and 85 years old;

[0084] (4) Subjects who are willing and able to participate in the trial.

[0085] 1.2.5 Exclusion Criteria

[0086] (1) Those who do not meet the diagnostic criteria;

[0087] (2) Those with serious heart, brain, liver, kidney, or lung diseases;

[0088] (3) Patients with other serious digestive system diseases that affect the diagnosis of this disease;

[0089] (4) Individuals with concurrent mental or neurological disorders or impaired consciousness;

[0090] (5) Pregnant or lactating women;

[0091] (6) Those who are under 18 years of age or over 85 years of age;

[0092] (7) Individuals with allergic constitutions or a history of adverse reactions to the test drug or its components;

[0093] (8) Those who cannot cooperate with the research and whose treatment efficacy cannot be judged;

[0094] (9) Those with poor compliance or who cannot be followed up on schedule for some reason.

[0095] 1.2.6 Exclusion Criteria

[0096] (1) Individuals who were mistakenly included in the trial but did not meet the inclusion criteria;

[0097] (2) Those who meet any of the exclusion criteria;

[0098] (3) Those who have not used medication since enrollment;

[0099] (4) Those with no follow-up visit records;

[0100] (5) Subjects who violate the protocol by changing medications or adding medications outside the prescribed range during the trial, especially those who use medications that may affect the evaluation of the investigational drug, thus affecting the judgment of efficacy and safety.

[0101] 1.2.7 Exit Criteria

[0102] (1) During the clinical trial, the subject developed certain comorbidities, complications or special physiological changes that made it unsuitable for the subject to continue the trial;

[0103] (2) Situations where serious adverse events or important adverse events occur, making it unsuitable to continue the trial;

[0104] (3) Subjects voluntarily withdraw from the trial midway, or subjects are lost to follow-up due to no longer receiving the investigational drug.

[0105] 2. Research Methods

[0106] 2.1 Treatment Plan

[0107] 2.1.1 Drugs

[0108] Using the traditional Chinese medicine composition of Example 1 of this invention as the therapeutic drug, the daily dosage of the herbal composition for adults is 85g (15g of Buzhaye, 10g of Jiubiying, 10g of Guanghuoxiang, 5g of Huanglian, 10g of Houpo, 15g of Fuling, 5g of Doukou, 5g of Fabanxia, ​​and 10g of Zhike). Granules of the herbal composition are prepared according to the method of Example 1 of this invention, with each bag containing 10g of granules (equivalent to 42.5g of the herbal composition per bag).

[0109] 2.1.2 Method of administration

[0110] Adults take one packet of granules with warm water one hour after a meal, twice a day.

[0111] 2.1.3 Treatment course: 4 weeks.

[0112] 2.1.4 Combined medication:

[0113] Discontinue any other medications related to the treatment of this disease during the treatment period.

[0114] 2.2 Observation Indicators

[0115] 2.2.1 General Information

[0116] General information about the case includes gender, age, region, course of disease, course of treatment, personal history, precipitating factors, comorbidities, and season of onset.

[0117] 2.2.2 Therapeutic Indicators

[0118] The efficacy was evaluated by assessing the improvement of TCM syndromes and individual symptoms after treatment. All symptoms were graded into four levels: none, mild, moderate, and severe. The primary symptom was scored as 0, 2, 4, and 6 points respectively, and the secondary symptom was scored as 0, 1, 2, and 3 points respectively.

[0119] 2.2.3 Safety Indicators

[0120] This mainly includes the occurrence of adverse reaction symptoms during the treatment of each case, as well as the data of liver function, kidney function, blood routine, urine routine, electrocardiogram and other indicators before and after treatment, based on which a safety evaluation is made.

[0121] 2.3 Criteria for Evaluating Therapeutic Effect

[0122] 2.3.1 Main therapeutic indicators

[0123] Using the overall efficacy of TCM syndromes as the main indicator of efficacy, the degree of improvement of various symptoms and signs after treatment was analyzed, along with a quantitative scoring table for TCM symptom grading. The total effective rate was calculated as: Total Effective Rate = (Number of cured cases + Number of cases with significant improvement + Number of cases with improvement) / Total Number of cases, and was divided into the following four levels:

[0124] (1) Clinical cure: The clinical symptoms and signs of TCM disappear or basically disappear, and the efficacy index is ≥95%.

[0125] (2) Significant effect: Clinical symptoms and signs in TCM are significantly improved, with 70% ≤ efficacy index < 95%.

[0126] (3) Effective: Clinical symptoms and signs in TCM patients all improved, with 30% ≤ efficacy index < 70%.

[0127] (4) Ineffective: The clinical symptoms and signs of TCM do not improve or even worsen, and the efficacy index is <30%.

[0128] 2.3.2 Secondary efficacy indicators

[0129] Using symptom-based efficacy as a secondary efficacy indicator, the degree of improvement of each individual symptom after treatment and the quantitative scoring table of TCM symptom grading were analyzed to calculate the total effective rate. The total effective rate = (number of cured cases + number of effective cases) / total number of cases, and was divided into the following four levels:

[0130] (1) Recovery: Symptoms disappear;

[0131] (2) Effective: ≥50% symptom improvement rate;

[0132] (3) Ineffective: symptom improvement percentage <50%;

[0133] (4) Worsening: The percentage of symptom improvement was negative.

[0134] The efficacy index / symptom improvement percentage = [(total score before treatment - total score after treatment) ÷ total score before treatment] × 100%.

[0135] 2.4 Safety Evaluation

[0136] The occurrence of adverse reaction symptoms during the treatment of each case was recorded. At the same time, the liver function, kidney function, blood routine, urine routine, electrocardiogram and other indicators before and after treatment of each case were recorded and compared to evaluate the safety of the drug of the present invention.

[0137] 2.5 Statistical Methods

[0138] A database was created using Excel 2016. SPSS 26.0 statistical software was used for data analysis. Quantitative data were expressed as mean ± standard deviation. Or the median and quartiles, i.e., [M(P 25 P 75 Data for count and ordinal data are expressed as frequency or proportion. For continuous data, paired t-tests or Wilcoxon signed-rank tests are used, with the Shapiro-Wilk test used to test for normality. For ordinal data, nonparametric rank-sum tests are used. A p-value < 0.05 indicates a statistically significant difference.

[0139] 3. Research Results

[0140] 3.1 General Information

[0141] 3.1.1 Gender Distribution

[0142] This study included a total of 220 cases, of which 127 were male (57.73%) and 93 were female (42.27%), with a male-to-female ratio of approximately 1.37:1.

[0143] 3.1.2 Age Distribution

[0144] Of the 220 patients included in this study, the age ranged from 21 to 83 years, with a mean age of 52.05 ± 12.73 years. The oldest male was 81 years old, the youngest was 21 years old, and the mean age was 50.36 ± 12.50 years; the oldest female was 83 years old, the youngest was 21 years old, and the mean age was 54.37 ± 12.74 years. The age distribution of patients was predominantly in the 41-50 age group (approximately 28.18%), followed by the 51-60 age group (24.55%) and the 61-70 age group (21.82%). See Table 3 for details.

[0145] Table 3. Age distribution of patients

[0146]

[0147] 3.1.3 Geographical Distribution

[0148] Of the 220 patients with chronic gastritis of the spleen and stomach damp-heat type included in this study, 137 (62.27%) were from Guangzhou and 83 (37.73%) were from outside the city.

[0149] 3.1.4 Disease course distribution

[0150] Of the 220 patients with chronic gastritis of the spleen and stomach damp-heat type included in this study, 206 had detailed disease courses recorded. The shortest course of disease was 0.1 months, the longest was 480 months, the median was 12 months, and the (P25, P75) ranged from (6, 48) months.

[0151] 3.1.5 Personal history, precipitating factors, and comorbidities

[0152] Among the 220 patients, 45 (20.45%) had a history of smoking, drinking alcohol, or drinking tea, as well as dietary preferences such as a preference for fatty, sweet, spicy, fried, or stimulating foods; 53 (24.09%) had obvious predisposing factors (poor diet, emotional imbalance, fatigue, high stress, or improper lifestyle) before the onset of the disease; 38 (17.27%) had Helicobacter pylori infection; 74 (33.64%) had gastrointestinal polyps; 23 (10.45%) had peptic ulcers; and 39 (17.73%) had gastroesophageal reflux disease.

[0153] 3.1.6 Seasonal Distribution of Disease Onset

[0154] Among the 220 patients with spleen and stomach damp-heat type chronic gastritis included, 69 cases (31.36%) developed the disease in spring (from the beginning of spring to the Grain Rain), 68 cases (30.91%) developed the disease in summer (from the beginning of summer to the Great Heat), 39 cases (17.73%) developed the disease in autumn (from the beginning of autumn to the Frost's Descent), and 44 cases (20.00%) developed the disease in winter (from the beginning of winter to the Great Cold). The majority of cases developed the disease in spring and summer.

[0155] 3.2 Distribution of clinical symptoms before treatment

[0156] In this study of 220 patients with chronic gastritis of the spleen and stomach damp-heat type, a total of 27 clinical symptoms were observed before treatment. Among them, bloating, belching, and stomach pain were the most frequent, occurring in 166 cases (75.45%), 152 cases (69.09%), and 120 cases (54.55%), respectively. See [link / reference]. Figure 1 .

[0157] 3.3 Results of therapeutic efficacy indicators

[0158] 3.3.1 Overall therapeutic effect after treatment

[0159] 3.3.1.1 Total TCM syndrome score before and after treatment

[0160] Among the 220 patients included, the total TCM syndrome score before treatment was 1907, and the total TCM syndrome score after treatment was 749. The difference in scores before and after treatment did not conform to a normal distribution. A Wilcoxon signed-rank test was used, and the results showed: Z = -12.548, P = 0.000 < 0.01. The decrease in the total TCM syndrome score before and after treatment was statistically significant, indicating that the TCM syndrome condition improved significantly after treatment. See Table 4.

[0161] Table 4 Comparison of total TCM syndrome scores before and after treatment

[0162]

[0163] 3.3.1.2 Overall therapeutic effect after treatment

[0164] A statistical analysis of the overall efficacy of treatment was conducted on 220 patients. Among them, 43 cases were cured, 53 cases showed significant improvement, 96 cases showed improvement, and 28 cases showed no improvement. The overall effective rate was 87.27%, and the cure rate was 19.55% (Table 5). The efficacy between different genders is shown in Table 6. Using the non-parametric Mann-Whitney U test, the results showed Z = -1.815, P = 0.070 > 0.05, indicating no significant difference in efficacy between genders. The efficacy between different age groups is shown in Table 7. Using the non-parametric Kruskal-Wallis H test, the results showed H = 3.799, P = 0.579 > 0.05, indicating no difference in efficacy between different age groups. The efficacy of different gastritis subtypes is shown in Table 8. Using the non-parametric Mann-Whitney U test, the results showed Z = -0.124, P = 0.901 > 0.05, indicating no difference in efficacy between different gastritis subtypes.

[0165] Table 5 Overall efficacy after treatment

[0166]

[0167] Table 6. Treatment efficacy for different genders

[0168]

[0169] Note: The nonparametric Mann-Whitney U test yielded P = 0.070.

[0170] Table 7. Therapeutic effects at different age groups

[0171]

[0172]

[0173] Note: According to the nonparametric Kruskal-Wallis H test, P = 0.579.

[0174] Table 8. Treatment efficacy for different types of gastritis

[0175]

[0176] Note: The nonparametric Mann-Whitney U test yielded P = 0.901.

[0177] 3.3.2 Treatment efficacy of each individual symptom after treatment

[0178] 3.3.2.1 Scores of each individual symptom before and after treatment

[0179] After treatment, the scores of all individual symptoms decreased compared to before treatment. Wilcoxon's signed-rank test and paired t-test both showed P < 0.01, indicating a statistically significant difference in the scores of each individual symptom after treatment compared to before treatment. This demonstrates that the condition of each individual symptom improved significantly after treatment. See Table 9.

[0180] Table 9. Scores of individual symptoms before and after treatment.

[0181]

[0182] Note: * P < 0.01 according to Wilcoxon signed-rank test; △ P < 0.01 according to paired t-test.

[0183] 3.3.2.2 Efficacy of individual symptoms after treatment

[0184] A statistical analysis of the efficacy of individual symptoms was conducted on 220 patients. The overall effective rate was 79.17% for stomach pain, 77.11% for bloating, and 69.59% for abnormal bowel movements. The overall effective rate for each individual symptom was over 60%. (See Table 10.)

[0185] Table 10. Treatment efficacy for each individual symptom after treatment.

[0186]

[0187]

[0188] 3.4 Security Analysis

[0189] Of the 220 patients, 32 underwent transaminase testing before and after treatment, 29 underwent alkaline phosphatase testing, 28 underwent gamma-glutamyl transferase testing, 27 underwent total bilirubin testing, 34 underwent renal function testing, 47 underwent complete blood count testing, 10 underwent urinalysis, and 41 underwent electrocardiogram (ECG) testing (see Table 11 for details). For cases where post-treatment indicators were clinically significant or not, a comparative analysis was performed before and after treatment for each patient, and the clinical significance of the indicators remained the same as before treatment. Two patients had ECGs indicating rapid atrial fibrillation and premature atrial contractions, respectively, before treatment; the clinical significance of their ECGs after treatment remained the same as before treatment, with no new changes observed.

[0190] Table 11 Safety indicators before and after treatment

[0191]

[0192]

[0193] 4. Conclusion

[0194] The traditional Chinese medicine composition of this invention can significantly improve the TCM syndrome and clinical symptoms of patients with chronic gastritis of the spleen and stomach damp-heat type, and has no adverse reactions and good safety.

[0195] Through long-term clinical application, the inventors have discovered that the following dosage ranges of raw materials in the herbal composition of this invention yield good results: 5-45 parts of *Broussonetia papyrifera* leaf, 5-30 parts of *Impatiens balsamina*, 5-30 parts of *Pogostemon cablin*, 3-15 parts of *Coptis chinensis*, 5-30 parts of *Magnolia officinalis*, 5-45 parts of *Poria cocos*, 3-15 parts of *Amomum villosum*, 3-15 parts of *Pinellia ternata*, and 5-30 parts of *Citrus aurantium*. For example, the dosage of *Broussonetia papyrifera* leaf can be 5, 10, 15, 30, or 40 parts; the dosage of *Impatiens balsamina* can be 5, 10, 15, or 30 parts; the dosage of *Coptis chinensis* can be 3, 5, 10, or 15 parts, etc. Other herbal compositions within the scope of this invention, such as the herbal compositions in Examples 2-5, also achieve good results for patients with chronic gastritis of the spleen and stomach damp-heat type.

[0196] Example 7

[0197] This embodiment is a pharmacodynamic study of the traditional Chinese medicine composition of the present invention on a rat model of chronic gastritis.

[0198] 1. Materials

[0199] 1.1 Laboratory Animals

[0200] 60 SPF male SD rats, weighing 180 - 220 g, were caged separately and fed. The room temperature was controlled at 22°C ± 2°C, and the humidity was 30 - 70%. The light / dark cycle was 12 h / 12 h. All rats were fed adaptively for 7 days before the experiment, with free access to food and water. The license number of the experimental SD rats was: SCXK(Xiang)2022 - 0011, and all animal experiments were approved by the Animal Ethics Committee (Animal Experiment Approval Number: LL202311011307).

[0201] 1.2 Reagents and Drugs

[0202] The traditional Chinese medicine composition was prepared according to the formula and method described in Example 1. After concentration, drying and pulverization, dry extract powder was obtained. Without adding other excipients, the dry extract powder was directly used in the experiment. The daily dosage of the traditional Chinese medicine composition tablets for adults is 85 g. According to the formula, the equivalent dose for rats was calculated to be 8.9 g / kg of the daily dosage, and the daily dosage for 250 g rats was 2.2 g / kg.

[0203] ELISA kits for rat tumor necrosis factor (tumor necrosis factor-α, TNF-α), interleukin-1β (Interleukin-1β, IL-1β), interleukin-10 (Interleukin-10, IL-10), and goat anti-rabbit IgG (purchased from Elabscience Biotechnology Co., Ltd., batch numbers were: E-EL-R2856c, E-EL-R0012c, E-EL-R0016c, E-AB-1034). p-JNK, JNK, p-ERK, ERK, p-P38, P38, β-actin, GAPDH (purchased from Wuhan Sanying Biotechnology Co., Ltd., batch numbers were: 80024-1-RR, 17572-1-AP, 28733-1-AP, 11257-1-AP, 28796-1-AP, 14064-1-AP, 20536-1-AP, 10494-1-AP). Pepsin activity detection kit (purchased from Solarbio Science & Technology Co., Ltd., batch number: BC2320).

[0204] 1.3 Instruments

[0205] Chemiluminescence analyzer, microplate reader, tissue homogenizer, refrigerated centrifuge

[0206] 2. Methods

[0207] 2.1 Animal Grouping, Modeling and Administration

[0208] Grouping: Sixty SD rats were randomly divided into six groups using a random number table: blank control group (control), model control group (Model), low-dose (HPXLD-L), medium-dose (HPXLD-M), high-dose (HPXLD-H) groups of the herbal composition of this invention, and omeprazole group (positive control group), with 10 rats in each group.

[0209] Modeling: Except for the blank control group, rats in all other groups were administered 56% ethanol solution by gavage to induce chronic gastritis. The gavage volume was 8 ml / kg, and water was withheld for 1 hour before each gavage. The intervention was carried out twice a week at a fixed time for a total of 4 weeks. The blank control group was given an equal volume of purified water at the same time point in the same manner.

[0210] Administration: After modeling, rats in the low, medium, and high dose groups of the herbal composition of this invention were administered 1, 2, and 4 times the clinical equivalent dose of the herbal composition of this invention via gavage, once daily at a volume of 2 ml / kg. The intervention duration was 14 days based on the preliminary experimental results. The positive control group was administered omeprazole 20 mg / kg via gavage at a volume of 2 ml / kg. The blank control group and the model control group were administered an equal volume of purified water. During the administration period, the model group, the omeprazole group, and the low, medium, and high dose groups of the herbal composition of this invention were simultaneously treated with 56% ethanol solution for modeling.

[0211] 2.2 Sample Collection and Processing

[0212] After the drug intervention, all rats in each group were fasted but allowed free access to water for 24 hours. Rats were anesthetized by intraperitoneal injection of 1.5% sodium pentobarbital solution at a dose of 0.2 mL / 100 g. Blood was collected from the abdominal aorta, incubated overnight at 4°C, and then centrifuged at 3000 rpm for 10 min to obtain serum. After blood collection, the entire stomach of the rat was removed and cut open along the greater curvature. The stomach contents were rinsed with physiological saline and blotted dry with filter paper. A portion of the stomach tissue was fixed in 4% paraformaldehyde for pathological examination, while another portion was used for molecular marker detection. The tissues were aliquoted and stored at -80°C.

[0213] 2.3 Observation of gastric tissue pathology and morphology

[0214] The fixed gastric tissue was embedded in paraffin, sectioned, dewaxed, stained with hematoxylin and eosin (HE), dehydrated and cleared with graded ethanol, and mounted with neutral resin. The pathological morphological changes of the gastric tissue in each group were observed using an optical microscope.

[0215] 2.4 Detection of serum TNF-α, IL-1β, and IL-6

[0216] Enzyme-linked immunosorbent assay (ELISA) was used for detection. Standards and sample diluent were added to the blank wells, and rat serum samples from each group (100 μL / well) were added to the remaining wells. The ELISA plate was covered and incubated at 37°C for 90 min. The liquid in the wells was discarded without washing, and 100 μL of biotinylated antibody working solution was added to each well. The ELISA plate was covered and incubated at 37°C for 60 min.

[0217] Wash the plate three times, add 100 μL of enzyme conjugation working solution to each well, cover the plate with a membrane, and incubate at 37°C for 30 min. Wash the plate five times, add 90 μL of substrate solution to each well, cover the plate with a membrane, and incubate at 37°C for 15 min. Add 50 μL of stop solution to each well to stop the reaction. After mixing, immediately measure the OD value of each well at 450 nm using a microplate reader.

[0218] 2.5 Assay of pepsin activity in gastric tissue

[0219] Take an appropriate amount of stomach tissue stored at -80℃, thaw at 4℃, and cut the stomach tissue into small pieces on ice. Add 9 times the volume of pre-cooled physiological saline, homogenize, centrifuge, and collect the supernatant. Use a BCA protein concentration assay kit to detect the protein concentration in the supernatant. Then, use the supernatant to detect the protein concentration in the stomach tissue according to the kit instructions.

[0220] 2.6 Detection of p-JNK / JNK, p-ERK / ERK, and p-P38 / P38 protein expression in gastric tissue

[0221] Take 20 mg of gastric tissue frozen at -80℃ (section 2.2), thaw at 4℃, add lysis buffer, grind and lyse the tissue on ice, centrifuge at 14000 r / min for 5 min, take the supernatant and determine the protein concentration using the BCA method, take 40 μg of protein for sample loading, electrophoresis, and membrane transfer reaction, add primary antibodies: p-JNK, JNK, p-ERK, ERK, p-P38, P38 (all diluted 1:1000), β-actin, and GAPDH internal control (1:5000), incubate overnight at 4℃, add goat anti-rabbit secondary antibody (1:5000), incubate at room temperature for 2 h, then develop color using enhanced chemiluminescence method, observe the bands and take pictures with a chemiluminescence analyzer, and analyze the relative expression level of each group of proteins (the ratio of the target protein to the internal control protein band) using Image-j software.

[0222] 2.7 Statistical Analysis

[0223] All data in this experiment are expressed as mean ± standard deviation. One-way ANOVA was performed using GraphPad Prism 8 statistical software. Data were analyzed at a significance level of α = 0.05, with P < 0.05 indicating statistical significance.

[0224] 3. Experimental Results

[0225] 3.1 Histopathological observation of the gastric mucosa of rats with chronic gastritis in low, medium and high dose groups of the traditional Chinese medicine composition of the present invention

[0226] according to Figure 2 As shown, the gastric mucosal epithelial structure of rats in the blank control group was clear, with normal number and morphology of glands, tightly and neatly arranged, and few inflammatory cell infiltrations. In the model group, the gastric mucosal epithelium of rats was significantly thinner, with a significant reduction in glands, which were loosely and randomly arranged, and many inflammatory cell infiltrations, indicating chronic inflammation of the gastric mucosa in the model group. In each drug intervention group, the gastric mucosal epithelium of rats thickened, glands increased, their morphology tended to be normal, their arrangement tended to be neat, and inflammatory cell infiltration decreased. Among these, the improvement effect of the traditional Chinese medicine composition of this invention on the pathological state of rat gastric mucosa was concentration-dependent, with the high-dose group showing the best effect, similar to the gastric mucosal state of the blank control group. This indicates that the positive control drug and the traditional Chinese medicine composition of this invention can improve chronic inflammation of the rat gastric mucosa, with the high-dose group showing the most significant effect.

[0227] 3.2 Effects of low, medium, and high dose groups of the herbal composition of the present invention on the expression levels of TNF-α, IL-1β, and IL-10 in the serum of rats with chronic gastritis

[0228] according to Figure 3 As shown, compared with the blank control group, the levels of TNF-α and IL-1β in the model control group were significantly increased (P<0.001), while the level of IL-10 in the model control group was significantly decreased (P<0.001). Compared with the model control group, the expression level of TNF-α was significantly decreased in the omeprazole group, the medium-dose group of the traditional Chinese medicine composition of the present invention, and the high-dose group (P<0.001), while there was no significant difference in the expression level of TNF-α in the low-dose group of the traditional Chinese medicine composition of the present invention (P>0.05). The expression level of IL-1β was significantly decreased in the omeprazole group and the medium-dose group of the traditional Chinese medicine composition of the present invention (P<0.001), while the expression level of IL-1β was significantly decreased in the low-dose group of the traditional Chinese medicine composition of the present invention (P<0.01). The expression level of IL-10 was significantly increased in the omeprazole group and the high-dose group of the traditional Chinese medicine composition of the present invention (P<0.001), the expression level of IL-10 was significantly increased in the medium-dose group of the traditional Chinese medicine composition of the present invention (P<0.01), and there was no significant difference in the expression level of IL-10 in the low-dose group of the traditional Chinese medicine composition of the present invention (P>0.05).

[0229] 3.3 Effects of low, medium, and high dose groups of the herbal composition of the present invention on pepsin activity in gastric tissue of rats with chronic gastritis

[0230] according to Figure 4As shown, compared with the blank control group, the pepsin activity in the model control group was significantly increased (P<0.001). Compared with the model control group, the pepsin activity in the omeprazole group and the high-dose group of the traditional Chinese medicine composition of the present invention was significantly decreased (P<0.001). The pepsin activity in the medium-dose group of the traditional Chinese medicine composition of the present invention was significantly decreased (P<0.01). There was no significant difference in IL-10 expression level in the low-dose group of the traditional Chinese medicine composition of the present invention (P>0.05).

[0231] 4. Conclusion

[0232] Studies have shown that the herbal composition of this invention can improve chronic inflammation of the gastric mucosa in rats with chronic gastritis, reduce the expression of TNF-α and IL-1β in serum, increase the expression of IL-10 in serum, and inhibit the activity of pepsin in gastric tissue, thereby exerting anti-inflammatory and gastric mucosal protective effects, and thus improving chronic gastritis.

[0233] In summary, the traditional Chinese medicine composition of the present invention can significantly improve the TCM syndrome and clinical symptoms of patients with chronic gastritis of the spleen and stomach damp-heat type, and has no adverse reactions and good safety.

[0234] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments 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.

[0235] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A traditional Chinese medicine composition for treating chronic gastritis due to damp-heat in the spleen and stomach, characterized in that, The active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 5-30 parts of Buzha leaf, 5-20 parts of Jiubiying, 5-20 parts of Guanghuoxiang, 3-10 parts of Huanglian, 5-20 parts of Houpo, 5-30 parts of Fuling, 3-10 parts of Doukou, 3-10 parts of Fabanxia, ​​and 5-20 parts of Zhike.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, The active ingredients of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 10-20 parts of Buzha leaf, 5-15 parts of Jiubiying, 5-15 parts of Guanghuoxiang, 5-10 parts of Huanglian, 5-15 parts of Houpo, 10-20 parts of Fuling, 5-10 parts of Doukou, 5-10 parts of Fabanxia, ​​and 5-15 parts of Zhike.

3. The method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 2, characterized in that, The preparation method includes the following steps: weighing the raw materials according to the formula, adding the extraction solvent, extracting, and collecting the extract.

4. The preparation method according to claim 3, characterized in that, The extraction includes decoction extraction, reflux extraction, maceration extraction, percolation extraction, distillation extraction, supercritical fluid extraction, ultrasonic extraction, and microwave extraction; and / or, the extraction solvent is water or an organic solvent.

5. The preparation method according to claim 4, characterized in that, The extraction is a decoction extraction, comprising the following steps: weighing the raw materials according to the formula, adding water and decocting 1 to 3 times; for the first decoction, adding 5 to 20 times the amount of water and decocting for 0.5 to 5 hours, collecting the volatile oil, and encapsulating it with 5 to 15 times the amount of beta-cyclodextrin to obtain a beta-cyclodextrin inclusion complex; filtering the decoction through an 80 to 200 mesh filter; adding 3 to 15 times the amount of water for the second and third decoctions respectively and decocting for 0.5 to 2 hours, and filtering the decoction through an 80 to 200 mesh filter; combining the filtrates, concentrating under reduced pressure at 60 to 70°C to obtain an extract with a relative density of 1.05 to 1.25, filtering through an 80 to 200 mesh filter, drying under vacuum at 60 to 70°C, and then adding the beta-cyclodextrin inclusion complex.

6. The use of the traditional Chinese medicine composition according to any one of claims 1 to 2 or the traditional Chinese medicine composition prepared by the preparation method according to any one of claims 3 to 5 in the preparation of a drug for treating chronic gastritis with damp-heat syndrome of spleen and stomach.

7. A medicine for treating chronic gastritis due to damp-heat in the spleen and stomach, characterized in that, The drug comprises a traditional Chinese medicine composition as described in any one of claims 1 to 2 or a traditional Chinese medicine composition prepared by any one of claims 3 to 5, and a pharmaceutically acceptable carrier.

8. The drug as described in claim 7, characterized in that, The dosage forms of the drugs include tablets, capsules, granules, pills, powders, syrups, creams, pills, oral liquids, tinctures, mixtures, lozenges, decoctions, medicated wines, teas, and extracts.

9. The drug as described in claim 7, characterized in that, The preparation method of the drug includes the following steps: adding the pharmaceutically acceptable carrier to the traditional Chinese medicine composition, mixing, and preparing the drug.

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