Application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and treatment of gastritis

Abstract

This invention discloses the application of a traditional Chinese medicine composition in the preparation of drugs for the prevention and treatment of gastritis. The composition comprises the following ingredients: Astragalus membranaceus, ginseng, Atractylodes macrocephala, fermented Cordyceps militaris powder, Lycium barbarum, Hedyotis diffusa, Fagopyrum dibotrys, Bistorta officinalis, Panax notoginseng, and Caesalpinia sappan. This invention is the first to discover and confirm that this traditional Chinese medicine composition can be used to prevent or treat chronic gastritis, especially chronic atrophic gastritis. Experiments have verified that it can significantly prevent or improve the pathological state of the gastric mucosa in rats with chronic atrophic gastritis. Specifically, it can significantly increase the serum pepsinogen I / II ratio, decrease gastrin-17 levels, reverse gastric gland atrophy, and repair the morphological structure of the gastric mucosa, achieving a systematic repair of the function and structure of the CAG gastric mucosa. Furthermore, the ingredients in this traditional Chinese medicine composition are rationally combined, and no obvious toxic side effects were observed under experimental conditions, demonstrating good safety and potential for long-term use.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to the application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and treatment of gastritis. Background Technology

[0002] Gastritis is one of the most common digestive system diseases in clinical practice, referring to inflammatory lesions of the gastric mucosa caused by various etiologies. Based on the course and pathological characteristics, it can be divided into two main categories: acute gastritis and chronic gastritis. The prevalence of chronic gastritis increases significantly with age, becoming a significant public health issue affecting national health. Chronic gastritis is further subdivided into chronic non-atrophic gastritis (formerly known as superficial gastritis) and chronic atrophic gastritis based on the characteristics of the gastric mucosal lesions. Chronic atrophic gastritis (CAG) is a chronic, progressive gastric mucosal lesion characterized by a reduction or disappearance of the intrinsic glands of the gastric mucosa. Its main pathological mechanism involves connective tissue hyperplasia caused by chronic inflammation (non-metaplastic atrophy), or the replacement of normal gastric glands by abnormal epithelium such as intestinal metaplasia (metaplastic atrophy). Clinically, CAG patients may be asymptomatic or present with discomfort such as stomach pain, epigastric fullness, and belching. The occurrence and development of this disease are related to multiple etiologies, including Helicobacter pylori infection, dietary habits, and genetic factors.

[0003] Currently, modern medical treatment for chronic atrophic gastritis (CAG) primarily focuses on acid suppression, gastric mucosal protection, and Helicobacter pylori eradication. While these methods can alleviate clinical symptoms to some extent, they still have limitations, such as the potential for adverse reactions from long-term use and the inability to completely halt disease progression. Traditional Chinese medicine (TCM) possesses unique theoretical advantages and clinical value in the prevention and treatment of CAG. Based on the principles of "holistic view" and "syndrome differentiation and treatment," the core pathogenesis of CAG in TCM is largely characterized by "deficiency of the root and excess of the branch," with "spleen and stomach weakness" as the root cause and "qi stagnation, damp-heat, and blood stasis" as the branch causes. TCM treatment emphasizes "strengthening the body's resistance and eliminating pathogenic factors, treating both the root and the branch," and through the comprehensive effects of multiple components and targets, it aims to reduce inflammatory responses, improve gastric mucosal microcirculation, promote mucosal repair, and regulate overall bodily functions, thereby reducing the risk of disease progression. However, currently, there are relatively few TCM preparations approved for the treatment of CAG in China (such as Weifuchun capsules / tablets), which falls far short of meeting actual clinical needs, resulting in a significant market gap.

[0004] Although some traditional Chinese medicine formulas for treating gastritis have been documented in related studies, their efficacy in reversing gastric mucosal atrophy and improving serum gastric function indicators in chronic gastritis (CAG) is limited, and systematic experimental verification is lacking. Therefore, developing a traditional Chinese medicine preparation capable of multi-target repair of gastric mucosal function and structure remains a pressing technical problem to be solved in clinical practice. Summary of the Invention

[0005] The present invention aims to at least solve one of the technical problems existing in the prior art. To this end, the present invention proposes the application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and treatment of gastritis.

[0006] According to one aspect of the present invention, an application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and treatment of gastritis is proposed, the traditional Chinese medicine composition comprising the following raw materials: Astragalus membranaceus, ginseng, Atractylodes macrocephala, fermented Cordyceps militaris powder, Lycium barbarum, Hedyotis diffusa, Fagopyrum diffusa, Bistorta officinalis, Panax notoginseng and Caesalpinia sappan.

[0007] This invention relates to a traditional Chinese medicine composition derived from an empirical formula developed by Professor Sun Guizhi of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, based on traditional Chinese medicine theory and long-term clinical practice. The entire formula is grounded in the TCM principle of "strengthening the body's resistance and nourishing its foundation," with a core focus on invigorating the spleen and replenishing qi. The combination of herbs is meticulously balanced, addressing both the symptoms and the root cause. Experiments have demonstrated that this composition can simultaneously improve serum gastric function indicators, reverse gastric gland atrophy, and repair the morphological structure of the gastric mucosa in CAG model rats through multiple targets and pathways, achieving a systematic repair of gastric mucosal function and structure.

[0008] According to some embodiments of the present invention, the drug for preventing and treating gastritis includes drugs for preventing and treating chronic gastritis.

[0009] According to some embodiments of the present invention, the drug for preventing and treating gastritis includes a drug for preventing and treating chronic atrophic gastritis.

[0010] According to some embodiments of the present invention, the raw materials of the traditional Chinese medicine composition are composed of the following components: Astragalus membranaceus, ginseng, Atractylodes macrocephala, fermented Cordyceps militaris powder, Lycium barbarum, Hedyotis diffusa, Fagopyrum cymosum, Bistorta officinalis, Panax notoginseng and Caesalpinia sappan.

[0011] According to some embodiments of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 5-20 parts of Astragalus membranaceus, 2-10 parts of Ginseng, 5-20 parts of Atractylodes macrocephala, 1-10 parts of fermented Cordyceps sinensis powder, 5-20 parts of Lycium barbarum, 10-25 parts of Hedyotis diffusa, 8-25 parts of Fagopyrum esculenta, 5-20 parts of Bistorta officinalis, 1-10 parts of Panax notoginseng, and 1-20 parts of Caesalpinia sappan.

[0012] According to some embodiments of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 5-20 parts of Astragalus membranaceus, 5-10 parts of Ginseng, 5-20 parts of Atractylodes macrocephala, 3-10 parts of fermented Cordyceps sinensis powder, 5-20 parts of Lycium barbarum, 10-25 parts of Hedyotis diffusa, 10-25 parts of Fagopyrum esculenta, 5-15 parts of Bistorta officinalis, 3-10 parts of Panax notoginseng, and 3-10 parts of Caesalpinia sappan.

[0013] According to some embodiments of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 12-18 parts of Astragalus membranaceus, 3-7 parts of Ginseng, 7-11 parts of Atractylodes macrocephala, 2-4 parts of fermented Cordyceps sinensis powder, 7-11 parts of Lycium barbarum, 12-18 parts of Hedyotis diffusa, 10-15 parts of Fagopyrum diffusa, 10-15 parts of Bistorta officinalis, 2-4 parts of Panax notoginseng, and 2-4 parts of Caesalpinia sappan.

[0014] According to some embodiments of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 15 parts Astragalus membranaceus, 5 parts Ginseng, 9 parts Atractylodes macrocephala, 3 parts fermented Cordyceps militaris powder, 9 parts Lycium barbarum, 15 parts Hedyotis diffusa, 12 parts Fagopyrum diffusa, 12 parts Bistorta officinalis, 3 parts Panax notoginseng, and 3 parts Caesalpinia sappan.

[0015] According to some embodiments of the present invention, the raw materials of the traditional Chinese medicine composition are composed of the following components in parts by weight: Astragalus membranaceus 5-20 parts, Ginseng 2-10 parts, Atractylodes macrocephala 5-20 parts, fermented Cordyceps sinensis powder 1-10 parts, Lycium barbarum 5-20 parts, Hedyotis diffusa 10-25 parts, Fagopyrum esculenta 8-25 parts, Bistorta officinalis 5-20 parts, Panax notoginseng 1-10 parts, and Caesalpinia sappan 1-20 parts.

[0016] According to some embodiments of the present invention, the raw materials of the traditional Chinese medicine composition are composed of the following components in parts by weight: Astragalus membranaceus 5-20 parts, Ginseng 5-10 parts, Atractylodes macrocephala 5-20 parts, fermented Cordyceps sinensis powder 3-10 parts, Lycium barbarum 5-20 parts, Hedyotis diffusa 10-25 parts, Fagopyrum esculenta 10-25 parts, Bistorta officinalis 5-15 parts, Panax notoginseng 3-10 parts, and Caesalpinia sappan 3-10 parts.

[0017] According to some embodiments of the present invention, the raw materials of the traditional Chinese medicine composition are composed of the following components in parts by weight: Astragalus membranaceus 12-18 parts, Ginseng 3-7 parts, Atractylodes macrocephala 7-11 parts, fermented Cordyceps sinensis powder 2-4 parts, Lycium barbarum 7-11 parts, Hedyotis diffusa 12-18 parts, Fagopyrum cymosum 10-15 parts, Bistorta officinalis 10-15 parts, Panax notoginseng 2-4 parts, and Caesalpinia sappan 2-4 parts.

[0018] According to some embodiments of the present invention, the raw materials of the traditional Chinese medicine composition are composed of the following components in parts by weight: 15 parts of Astragalus membranaceus, 5 parts of Ginseng, 9 parts of Atractylodes macrocephala, 3 parts of fermented Cordyceps militaris powder, 9 parts of Lycium barbarum, 15 parts of Hedyotis diffusa, 12 parts of Fagopyrum diffusa, 12 parts of Bistorta officinalis, 3 parts of Panax notoginseng, and 3 parts of Caesalpinia sappan.

[0019] According to some embodiments of the present invention, the raw material is in powder form.

[0020] According to some embodiments of the present invention, the traditional Chinese medicine composition includes an extract of the raw material.

[0021] According to some embodiments of the present invention, the extraction solvent of the extract includes at least one of water or an organic solvent (such as alcohol).

[0022] According to some embodiments of the present invention, the extraction method of the extract includes the following steps: take the raw material, add 6-20 times the amount of water, decoct 2-3 times, each time for 1-2 hours, separate the solid and liquid phases, collect the liquid phases and combine them to obtain the extract.

[0023] According to some embodiments of the present invention, the extraction method of the extract further includes concentrating the collected liquid phase to a relative density of 1.05-1.30 and drying it to obtain the extract.

[0024] According to some embodiments of the present invention, the temperature of the concentration process is 60-70°C.

[0025] According to some embodiments of the present invention, the drying is performed by spray drying.

[0026] According to some embodiments of the present invention, the traditional Chinese medicine composition serves as the active ingredient in a drug for the prevention and treatment of gastritis.

[0027] According to some embodiments of the present invention, the traditional Chinese medicine composition is the sole active ingredient in a drug for the prevention and treatment of gastritis.

[0028] According to some embodiments of the present invention, the administration method of the drug for preventing and treating gastritis includes at least one of oral, gavage, or injection (such as intravenous injection, subcutaneous injection, intramuscular injection, etc.).

[0029] According to some embodiments of the present invention, the dosage of the drug for preventing and treating gastritis is 100-5000 mg / kg, wherein the dosage is based on the solid mass of the traditional Chinese medicine composition.

[0030] According to some embodiments of the present invention, the dosage of the drug for preventing and treating gastritis is 1000-4800 mg / kg, wherein the dosage is based on the solid mass of the traditional Chinese medicine composition.

[0031] According to some embodiments of the present invention, the administration cycle of the drug for preventing and treating gastritis is 1-5 times per day.

[0032] According to some embodiments of the present invention, the administration cycle of the drug for preventing and treating gastritis is 1-3 times per day.

[0033] According to some embodiments of the present invention, the raw materials for preparing the drug further include pharmaceutically acceptable excipients. The above-mentioned traditional Chinese medicine composition can be prepared into conventional oral dosage forms such as granules, capsules, tablets, pills, ointments, oral liquids, or syrups, or into injections or oral boluses.

[0034] According to some embodiments of the present invention, the excipients include at least one of excipients, emulsifiers, stabilizers, binders, preservatives, diluents, buffers, pH adjusters, or flavoring agents.

[0035] According to some embodiments of the present invention, the excipient is selected from at least one of microcrystalline cellulose, lactose, pregelatinized starch, cyclodextrin, carboxymethyl cellulose, mannitol, magnesium stearate, starch, calcium phosphate, ethyl cellulose, methyl cellulose, alginate, gelatin, gum arabic, glyceryl monostearate, sodium glycolate starch, guar gum, glycerol, or propylene glycol.

[0036] According to some embodiments of the present invention, the emulsifier is selected from at least one of magnesium stearate, zinc stearate, calcium stearate, glyceryl stearate, sorbitan isostearate, sorbitan oleate, glyceryl oleate, or polyglycerol-3 polyricinoleate.

[0037] According to some embodiments of the present invention, the stabilizer is selected from at least one of acacia gum, agar, alginate, cellulose ether or carboxymethyl chitosan.

[0038] According to some embodiments of the present invention, the adhesive is selected from at least one of ethanol, starch paste, pregelatinized starch, dextrin, syrup, hydroxypropyl methylcellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyvinyl alcohol, polyethylene glycol, sodium alginate, polyvinylpyrrolidone, gum arabic, gelatin, or alginic acid.

[0039] According to some embodiments of the present invention, the preservative is selected from at least one of methylparaben, propylparaben, methylparaben, ethylparaben, propylparaben, chlorobutanol, phenoxyethanol, chlorhexidine, benzoic acid, sodium benzoate, chlorocresol, benzalkonium bromide, or ethylparaben.

[0040] According to some embodiments of the present invention, the diluent is selected from at least one of erythritol, mannitol, sorbitol, xylitol, lactose, sucrose, corn starch, potato starch, calcium phosphate, calcium citrate, or crystalline cellulose.

[0041] According to some embodiments of the present invention, the buffer is selected from at least one of sodium dihydrogen phosphate, sodium bicarbonate, ammonium bicarbonate, sodium acetate, citrate, histidine, or succinate.

[0042] According to some embodiments of the present invention, the pH adjuster is selected from at least one of citric acid, fumaric acid, succinic acid, tartaric acid, malic acid, or ascorbic acid.

[0043] According to some embodiments of the present invention, the flavoring agent is selected from at least one of sweet orange flavoring, vanilla flavoring, strawberry flavoring, milk flavoring, banana flavoring, or cherry flavoring.

[0044] According to some embodiments of the present invention, the dosage form of the drug for preventing and treating gastritis is an oral preparation.

[0045] According to some embodiments of the present invention, the dosage form of the drug for preventing and treating gastritis is granules. The traditional Chinese medicine composition of the present invention is based on the TCM treatment principle of "strengthening the body's resistance and nourishing its foundation," and is developed targeting the core pathogenesis of CAG (congenital atrophic gastritis) characterized by deficiency of the root cause and excess of the symptoms. Its granule dosage form facilitates long-term use and management by patients, and is suitable for medical settings such as hospitals at all levels, community health service centers, and home self-medication. The present invention provides another effective traditional Chinese medicine preparation for the drug treatment of CAG.

[0046] According to some embodiments of the present invention, the preparation steps of the granules are as follows: the composition is mixed with excipients, stirred and granulated, or dried and then subjected to fluidized bed granulation and granulation to obtain the granules.

[0047] According to some embodiments of the present invention, the stirring granulation process includes the following parameters: stirring speed 380-420 rpm, and chopping speed 600-650 rpm.

[0048] According to some embodiments of the present invention, the drying is carried out by spray drying, which includes the following parameters: air inlet temperature 90-150°C; air outlet temperature 60-90°C.

[0049] According to some embodiments of the present invention, the fluidized bed granulation includes the following parameters: inlet air temperature 60-90°C, outlet air temperature 30-50°C.

[0050] According to some embodiments of the present invention, the drug for preventing and treating gastritis can improve the morphology and pathological structure of the gastric mucosa. The drug for preventing and treating gastritis can improve the macroscopic morphology and pathological structure of the gastric mucosa.

[0051] According to some embodiments of the present invention, the drug for preventing and treating gastritis can delay or improve gastric gland atrophy.

[0052] According to some embodiments of the present invention, the drug for preventing and treating gastritis can delay or improve the degree of gastric mucosal lesions.

[0053] According to some embodiments of the present invention, the drug for preventing and treating gastritis can regulate the levels of biomarkers related to gastric mucosal function.

[0054] According to some embodiments of the present invention, the gastric mucosal function-related biomarkers include serum gastric function indicator biomarkers.

[0055] According to some embodiments of the present invention, the serum gastric function biomarkers include at least one of pepsinogen I (PG I), pepsinogen II (PG II), and gastrin-17 (G-17). For example, increasing PG I levels optimizes the PG I / PG II ratio while decreasing G-17 levels.

[0056] According to some embodiments of the present invention, the biomarker content that can regulate gastric mucosal function includes at least one of the following indicators: 1) increasing serum pepsinogen I / II ratio; 2) decreasing serum gastrin-17 level.

[0057] According to some embodiments of the present invention, the drug for preventing and treating gastritis can simultaneously improve the macroscopic morphology and pathological structure of the gastric mucosa, delay or improve gastric gland atrophy and the degree of gastric mucosal lesions, and regulate the content of gastric mucosal function-related biomarkers.

[0058] According to some embodiments of the present invention, the fungal species to which the fermented Cordyceps powder belongs may be Paecilomyces hepiali or Trichoderma hepiali.

[0059] The present invention has the following beneficial effects: 1. It produced an unexpected, specific repair effect on the gastric mucosa. This invention, through a CAG model rat experiment (5.5 months of continuous composite modeling), demonstrates for the first time that the traditional Chinese medicine composition can produce the following three gastric mucosal repair effects, which are neither disclosed in the anti-tumor use of the prior art nor reasonably expected: (1) Repairing gastric mucosal secretory function: In a rat model of chronic atrophic gastritis (CAG), the YWKL administration group significantly increased PGI and significantly decreased PGII, thereby significantly increasing PGR value; at the same time, it significantly reduced the abnormally elevated G-17 level. This indicates that the composition can effectively correct the disorder of CAG-related serum biomarkers, suggesting that it has a positive regulatory effect on gastric mucosal secretory function.

[0060] (2) Reversal of gastric gland atrophy: The average score of gastric gland atrophy in each YWKL administration group was lower than that in the model group, with the reversal rate of the low and medium dose groups being as high as 83.3% and 75.0%, respectively. This indicates that the composition can effectively reverse the characteristic glandular atrophy lesions of CAG.

[0061] (3) Repairing the morphological structure of the gastric mucosa: In the model group, the gastric mucosa was thinner, the number of glands was significantly reduced, and the arrangement was disordered; in the YWKL administration group, the gastric glands were atrophied and the structure was more intact, with mild inflammatory infiltration.

[0062] 2. It has a different mechanism of action than its anti-tumor uses. In the therapeutic use of the traditional Chinese medicine composition of the present invention for CAG, the spleen-tonifying and qi-boosting drugs such as Astragalus membranaceus, ginseng, Atractylodes macrocephala, and fermented Cordyceps sinensis powder play a leading role, and the composition works by repairing the gastric mucosal barrier and regulating gastric secretion function.

[0063] 3. Good security No obvious toxic side effects were observed under experimental conditions, indicating its potential for long-term use.

[0064] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0065] Figure 1 This is a comparison chart of changes in serum gastric function indicators in rats before and after intervention with the traditional Chinese medicine composition. AD represents the comparison of PGI, PGII, PGR, and G-17 levels. Data are expressed as mean ± SEM. NC, n=12; Model, yu-YWKL-M, n=6; yu-WFC, n=7; yu-YWKL-M, yu-YWKL-H, n=8; YWKL-L, YWKL-M, n=10; YWKL-H, n=11; WFC, n=9. P<0.01, P < 0.001, P < 0.0001, compared with the model group.

[0066] Figure 2 This is a representative image of the histopathological morphology (HE staining) of the gastric body mucosa in each group of rats during tissue sample analysis. Yellow arrows indicate mucosal epithelial cell shedding; orange arrows indicate gastric gland atrophy; brown arrows indicate connective tissue hyperplasia; blue arrows indicate lymphocyte and granulocyte infiltration; focal edema in the submucosa; purple arrows indicate loose connective tissue arrangement; and blue arrows indicate gastric gland dilatation. The normal control group (NC) showed a thick mucosa with densely packed and neatly arranged gastric glands, without atrophy or inflammation.

[0067] Figure 3This figure shows the results of the analysis of the improvement and reversal rate of gastric mucosal atrophy and overall lesion severity in CAG rats in each group. A: Comparison of average scores for gastric gland atrophy in each group; B: Effective reversal rate based on atrophy score; C: Comparison of average scores for overall gastric mucosal lesion severity in each group; D: Effective reversal rate based on lesion score. Data are expressed as mean ± SEM: NC, n=12; Model, n=7; yu-YWKL-L, n=6; yu-YWKL-M, n=8; yu-YWKL-H, n=8; yu-WFC, n=7; YWKL-L, n=9; YWKL-M, n=10; YWKL-H, n=11; WFC, n=7. P<0.05, P<0.01, P < 0.001, P < 0.0001, compared with the model group. Detailed Implementation

[0068] The following will clearly and completely describe the concept and technical effects of the present invention in conjunction with embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention. Unless otherwise specified, the experimental methods used in the embodiments are conventional methods; the materials and reagents used, unless otherwise specified, are commercially available. Unless otherwise specified, the same parameter value is the same in all embodiments. The embodiments described below are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0069] In the description of this invention, references to terms such as "some embodiments" indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0070] The term "prevention and control" as used in this invention refers to measures for prevention and / or treatment, including treatment of diseases that have already occurred and preventive treatment of diseases that have not yet occurred.

[0071] All the animal experiments described below were approved by the Ethics Committee of Jiangzhong Pharmaceutical Co., Ltd. (License No.: 20250225) and strictly followed the ARRIVE guidelines. Mice were housed under standard environmental conditions (temperature 23±2℃, humidity 50±10%, 12h / 12h light-dark cycle) and had free access to standard rodent feed and water.

[0072] The experimental results in the following examples were verified using 400 SPF-grade SD rats, half male and half female, weighing 180-220g. After one week of acclimatization, the rats were randomly divided into groups.

[0073] In the following examples, the raw materials used as raw materials, including Astragalus membranaceus, ginseng, Atractylodes macrocephala, fermented Cordyceps militaris powder, Lycium barbarum, Hedyotis diffusa, Fagopyrum dibotrys, Bistorta officinalis, Panax notoginseng, and Caesalpinia sappan, were all commercially available Chinese medicinal herbs. The fermented Cordyceps militaris powder was specifically fermented Cordyceps militaris powder CS-4.

[0074] Example This example provides the application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and treatment of gastritis. The composition is obtained by water extraction from the following raw materials: Astragalus membranaceus, ginseng, Atractylodes macrocephala, fermented Cordyceps militaris powder, Lycium barbarum, Hedyotis diffusa, Fagopyrum diffusa, Bistorta officinalis, Panax notoginseng, and Caesalpinia sappan. Specifically, the preparation process is as follows: Take 15g of Astragalus membranaceus, 5g of ginseng, 9g of Atractylodes macrocephala, 9g of Lycium barbarum, 3g of fermented Cordyceps militaris powder, 12g of Bistorta officinalis, 12g of Fagopyrum diffusa, 15g of Hedyotis diffusa, 3g of Panax notoginseng, and 3g of Caesalpinia sappan. Add water and decoct twice, each time adding water at a rate of 6 times the total mass of the medicinal herbs. Each decoction lasts for 1 hour. After decoction, filter, combine the water extracts, concentrate under reduced pressure to a relative density of 1.12 (temperature controlled at 65℃), and spray dry to obtain the final product.

[0075] The above-mentioned traditional Chinese medicine composition (referred to as "YWKL") was used to prevent or treat chronic atrophic gastritis in rats.

[0076] The effects of the preventive administration (pre-administration) and therapeutic administration (simultaneous administration) of the present invention were investigated separately. Ten groups were designed as follows, with 40 animals (half male and half female) in each group. The group numbers, names and treatment descriptions are shown in Table 1 below.

[0077] Table 1

[0078] 1. Modeling Specifically, a composite molding method is used, as detailed below: Except for the NC group, the other groups used the following combined method for modeling, which lasted for about 6 months: Feed: Feed containing 0.03 wt% ranitidine.

[0079] Drinking water: Free access to a mixture of 100 μg / mL MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) solution and 0.1 vol% ammonia water.

[0080] Eating rhythm: Alternate between two days of heavy eating and two days of fasting.

[0081] Periodic gavage modeling: On each "day 2 of full feeding and day 2 of fasting", a mixed solution of 2wt% sodium salicylate and 300 μg / mL MNNG was administered by gavage, with a gavage volume calculated at 10 mL / kg body weight. The treatment group did not receive any medication on the day of gavage modeling, but received the corresponding dose of drug solution via gavage daily at other times.

[0082] 2. Dosage The dosage is as follows: High, medium, and low doses (denoted as "YWKL-H / M / L"): Low dose (denoted as "YWKL-L"): 0.115 g / mL.

[0083] Medium dose (denoted as "YWKL-M"): 0.229 g / mL.

[0084] High dose (denoted as "YWKL-H"): 0.459 g / mL.

[0085] Positive control drug: Weifuchun capsules (referred to as "WFC") (Hangzhou Huqingyutang Pharmaceutical Co., Ltd., batch number: 24111164).

[0086] Dosage: 43.40 mg / mL.

[0087] All of the above were administered via gavage in volumes of 100 g body weight / mL.

[0088] 3. Sample collection: Animals were euthanized in batches at the end of the 2nd, 4th, 5th and 6th months after modeling and drug administration, with 6-8 animals taken from each group each time.

[0089] 1) Blood sample: Blood was drawn from the abdominal aorta, and serum was separated for the detection of gastric function indicators.

[0090] The specific details of serum gastric function index testing (non-invasive assessment "serum gastroscopy") are as follows: Serum pepsinogen (PG) and gastrin-17 (G-17) testing, clinically known as "serum gastroscopy," is a mature method recommended in the "Chinese Consensus on Chronic Gastritis" and the "Technical Guidelines for Clinical Efficacy Evaluation of New Traditional Chinese Medicine Drugs for Chronic Gastritis (Trial Implementation)" for gastric cancer screening and non-invasive assessment of gastric mucosal status (especially atrophy). These guidelines explicitly state that for drugs aimed at improving gastric mucosal atrophy, these indicators can be considered as efficacy assessment indicators.

[0091] PGI (pepsinogen I): mainly secreted by the chief cells of the gastric body (fundus glands). A sign of functional atrophy: a decrease reflects atrophy of the gastric fundus / body mucosal glands and a reduction in the number of chief cells.

[0092] PGII (pepsinogen II): It is related to the overall gastric mucosal condition and is a broad-spectrum indicator of mucosal condition. It may be elevated during periods of inflammation and infection, and may also be elevated under inflammatory conditions such as Helicobacter pylori infection.

[0093] PGR (PGI / PGII): A sensitive and specific core indicator for diagnosing gastric mucosal atrophy. A decrease in the ratio is a key marker of model success, while its recovery directly reflects the functional reversal of atrophic lesions.

[0094] Gastrin-17 (G-17): Secreted by G cells in the gastric antrum. When the gastric antrum atrophies, the number of G cells decreases, and its level drops; when atrophy is predominant in the gastric body, it may increase due to negative feedback. Gastric antrum function and atrophy localization landmarks: Help determine the location of atrophy.

[0095] Serum gastric function index detection method: The concentrations of PGI, PGII and G-17 in rat serum were detected by ELISA method strictly in accordance with the kit instructions, and the PGR value was calculated. The calculation method is consistent with that in clinical practice.

[0096] The test results of the pre-drug group and the drug-dosed group are as follows: Figure 1 As shown. From Figure 1 As can be seen, compared with the NC group, the Model group (Model) showed significantly lower PGI and PGR, and significantly higher PGII and G-17. P < 0.0001. YWKL intervention showed a significant dose-dependent improvement: compared to the model group, both the pre-administration and administration groups of YWKL significantly increased PGI and significantly decreased PGII, thereby significantly improving PGR values ​​(P < 0.0001). P < 0.0001. Meanwhile, YWKL significantly reduced abnormally elevated G-17 levels (P < 0.0001). P<0.01, (P < 0.001). The results show that the herbal composition of the present invention can effectively correct the disorder of serum biomarkers related to CAG, suggesting that it has a positive regulatory effect on gastric mucosal secretion function and internal environment homeostasis.

[0097] 2) Tissue samples: The stomach tissue was completely removed, cut along the greater curvature of the stomach, rinsed with physiological saline, flattened for observation, and fixed for pathological examination.

[0098] The pathological "gold standard" of evaluation, combining gastroscopy with mucosal biopsy, was used. The specific steps are as follows: ① Sample preparation and staining: Rat stomach tissue was taken, cut along the greater curvature of the stomach, rinsed with physiological saline, and flattened. It was fixed in 4% paraformaldehyde, routinely embedded in paraffin, and sectioned to a thickness of 4 μm. After dewaxing and hydration, the sections were stained with hematoxylin and eosin (HE) and mounted with neutral resin. ② Pathological observation and semi-quantitative analysis: Independent scoring was conducted by a third-party pathologist, and observation was performed independently under an optical microscope. Histological changes in the gastric mucosa were semi-quantitatively assessed using a recognized pathological scoring system for chronic gastritis (such as the Sydney system or its modified version). Key observation indicators included: degree of chronic inflammation, inflammatory activity, gastric glandular atrophy, intestinal metaplasia, and dysplasia. Each indicator was graded from 0 to 3 (0 for none, 3 for the most severe). As a preferred scoring method, the specific histological characteristics corresponding to each grade can be defined as follows: 0 points (None): Histological findings are normal, with no corresponding pathological features; 1 point (mild): The lesion is localized, scattered or focal, and the range is less than 1 / 3 of the observation area; 2 points (moderate): The lesion is diffuse or obvious, and its range is between 1 / 3 and 2 / 3 of the observed area; 3 points (severe): The lesions are extensive, diffuse or significant, covering more than 2 / 3 of the observed area, or accompanied by severe structural damage.

[0099] To comprehensively assess the effectiveness of gastric mucosal repair, a Total Severity of Disease (THS) score is calculated using the following formula: THS = (Chronic Inflammation Severity Score + Inflammation Activity Score + Gastric Glandular Atrophy Score + Intestinal Metaplasia Score). Based on the THS score range, the overall lesion is categorized as follows: 0-2: None / Very Mild; 3-5: Mild; 6-8: Moderate; 9-12: Severe.

[0100] from Figure 2As can be seen, in the model group (Model): the mucosa is thinner, the number of glands is significantly reduced (atrophy), the arrangement is disordered, and inflammatory cell infiltration is observed in the lamina propria. In the positive control group (WFC): glandular atrophy and inflammatory infiltration are reduced compared to the model group. In the group treated with the herbal composition of this invention (YWKL): glandular atrophy is improved, the structure is more intact, and inflammatory infiltration is mild. Histopathological observation directly confirms the success of the model and the efficacy of the herbal composition of this invention. Therefore, the herbal composition of this invention can significantly promote the repair of atrophic gastric glands, increase glandular density and structural integrity, and reduce inflammatory cell infiltration in the mucosal layer through prevention and treatment, morphologically demonstrating its potential to reverse the core pathological changes of CAG.

[0101] 3) Reversal rate analysis: To quantify the proportion of individuals with clear pathological improvement, the following criteria were set for determining the reversal rate: Effective reversal of gastric gland atrophy: GA score ≤ 1. This threshold is based on the mean atrophy score of the model group (1.88), representing a reversal from the model's average "mild to moderate atrophy" state to "no / mild atrophy" (score reduction ≥ 0.88 points, i.e., ≥ 1 grade). Effective reversal of overall lesions: THS score ≤ 3. This threshold is based on the mean lesion score of the model group (4.75), representing a reversal from "mild lesions" to "no / very mild lesions" (score reduction ≥ 1.75 points, i.e., ≥ 2 grades). Reversal rate calculation formula: (Number of animals with effective reversal in the group / Total number of animals in the group) × 100%.

[0102] Analysis results as follows Figure 3 As shown, the pathological scoring results further clarified the efficacy of the herbal composition in this invention. The figure shows that, regarding gastric mucosal atrophy, the average scores of all YWKL administration groups were lower than the model group (A), with the lowest scores in the pre-administered low and medium dose groups. Regarding atrophy reversal rates, the reversal rates of the YWKL low, medium, and high dose groups in the pre-administered groups (83.3%, 75.0%, 75.0%) were significantly higher than those of the positive control drug Weifuchun group (42.9%); simultaneously, the reversal rates of the YWKL low and medium dose groups (55.6%, 60.0%) were comparable to or better than those of the positive control drug (57.1%) (B). In terms of overall lesion severity, the trends were similar (C), with the lesion reversal rate in the YWKL pre-administered low dose group reaching as high as 83.3%. All doses showed stable efficacy in both prevention and treatment modes, with reversal rates ranging from 54.5% to 83.3% (D). This indicates that the herbal composition of the present invention can effectively reduce the gastric mucosal atrophy lesion score, effectively reverse the pathological state in most individuals, and has a clear advantage over Weifuchun.

[0103] The embodiments of the present invention have been described in detail above, but the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention.

Claims

1. The application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and treatment of gastritis, characterized in that: The traditional Chinese medicine composition includes the following raw materials: Astragalus membranaceus, ginseng, Atractylodes macrocephala, fermented Cordyceps militaris powder, Lycium barbarum, Hedyotis diffusa, Fagopyrum dibotrys, Bistorta officinalis, Panax notoginseng, and Caesalpinia sappan; the drug for preventing and treating gastritis includes a drug for preventing and treating chronic atrophic gastritis; the traditional Chinese medicine composition includes the following raw materials in parts by weight: Astragalus membranaceus 5-20 parts, ginseng 2-10 parts, Atractylodes macrocephala 5-20 parts, fermented Cordyceps militaris powder 1-10 parts, Lycium barbarum 5-20 parts, Hedyotis diffusa 10-25 parts, Fagopyrum dibotrys 8-25 parts, Bistorta officinalis 5-20 parts, Panax notoginseng 1-10 parts, and Caesalpinia sappan 1-20 parts.

2. The application according to claim 1, characterized in that: The traditional Chinese medicine composition comprises the following raw materials in parts by weight: Astragalus membranaceus 5-20 parts, Ginseng 5-10 parts, Atractylodes macrocephala 5-20 parts, fermented Cordyceps sinensis powder 3-10 parts, Lycium barbarum 5-20 parts, Hedyotis diffusa 10-25 parts, Fagopyrum cymosum 10-25 parts, Bistorta officinalis 5-15 parts, Panax notoginseng 3-10 parts, and Caesalpinia sappan 3-10 parts.

3. The application according to claim 1, characterized in that: The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 15 parts Astragalus membranaceus, 5 parts Ginseng, 9 parts Atractylodes macrocephala, 3 parts Fermented Cordyceps sinensis powder, 9 parts Lycium barbarum, 15 parts Hedyotis diffusa, 12 parts Fagopyrum diffusa, 12 parts Bistorta officinalis, 3 parts Panax notoginseng, and 3 parts Caesalpinia sappan.

4. The application according to claim 1, characterized in that: The raw materials of the traditional Chinese medicine composition are composed of the following components in parts by weight: Astragalus membranaceus 5-20 parts, Ginseng 2-10 parts, Atractylodes macrocephala 5-20 parts, fermented Cordyceps sinensis powder 1-10 parts, Lycium barbarum 5-20 parts, Hedyotis diffusa 10-25 parts, Fagopyrum diffusa 8-25 parts, Bistorta officinalis 5-20 parts, Panax notoginseng 1-10 parts, and Caesalpinia sappan 1-20 parts.

5. The application according to claim 1, characterized in that: The raw materials of the traditional Chinese medicine composition are composed of the following ingredients in parts by weight: 15 parts Astragalus membranaceus, 5 parts Ginseng, 9 parts Atractylodes macrocephala, 3 parts Fermented Cordyceps sinensis powder, 9 parts Lycium barbarum, 15 parts Hedyotis diffusa, 12 parts Fagopyrum diffusa, 12 parts Bistorta officinalis, 3 parts Panax notoginseng, and 3 parts Caesalpinia sappan.

6. The application according to claim 1, characterized in that: The traditional Chinese medicine composition includes an extract of the raw material, and the extraction solvent of the extract includes at least one of water or an organic solvent.

7. The application according to claim 1, characterized in that: The administration method of the drug for preventing and treating gastritis includes at least one of oral, gavage, or injection; and / or, the dosage of the drug for preventing and treating gastritis is 100-5000 mg / kg, the dosage being based on the solid mass of the traditional Chinese medicine composition.

8. The application according to claim 1, characterized in that: The medication used to prevent and treat gastritis can improve the morphology and pathological structure of the gastric mucosa.

9. The application according to claim 1, characterized in that: The drug for the prevention and treatment of gastritis has at least one of the following functions: 1) it can delay or improve gastric gland atrophy; 2) it can delay or improve the degree of gastric mucosal lesions; 3) it can regulate the content of gastric mucosal function-related biomarkers.

10. The application according to claim 9, characterized in that: The levels of biomarkers that can regulate gastric mucosal function include at least one of the following indicators: 1) increased serum pepsinogen I / II ratio; 2) decreased serum gastrin-17 level.

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