A traditional Chinese medicine composition for treating chronic atrophic gastritis and a preparation method thereof

Abstract

The present application relates to a kind of traditional Chinese medicine composition for treating chronic atrophic gastritis and its preparation method, the traditional Chinese medicine composition contains the following mass parts of raw materials: 9-30 parts of Huangqi, 6-9 parts of vinegar Eupolyphaga, 10-15 parts of dandelion, 5-10 parts of Pu Huang, 6-12 parts of dendrobium, 5-10 parts of earth peony, 6-30 parts of white flower snake tongue grass, 9-30 parts of oyster, 3-10 parts of fried chicken inner gold, 3-10 parts of Magnolia officinalis.The effect is investigated by the gastric precancerous lesion cell model constructed by MNNG, and the results show that the traditional Chinese medicine composition has certain therapeutic effect on chronic atrophic gastritis, and the specific performance is to promote the apoptosis of abnormal proliferation, improve cell stemness and epithelial-mesenchymal transition and other malignant changes.

Description

Technical Field

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

[0002] Stomach cancer is the fifth most common malignant tumor and the third most deadly tumor in my country. According to data from the National Cancer Center in 2024, there were 358,700 new cases of stomach cancer and more than 260,000 deaths annually in my country, seriously threatening the health and lives of the Chinese people. How to reduce the incidence of stomach cancer is one of the public health issues that urgently need to be addressed.

[0003] 50-80% of gastric cancers are intestinal-type gastric cancers, which evolve through multiple stages of pathological changes: "normal gastric mucosa → chronic non-atrophic gastritis → chronic atrophic gastritis → intestinal metaplasia → dysplasia → gastric cancer".

[0004] At present, the treatment of chronic gastritis-cancer transformation mainly focuses on symptomatic treatment, regular endoscopic follow-up, and endoscopic treatment. There is still a lack of drugs that can effectively reverse the pathological state of the gastric mucosa. Although Helicobacter pylori eradication has a positive effect on atrophic gastritis, its efficacy is limited for those that have progressed to the precancerous stage. Single-target inhibitors (such as COX-2 inhibitors) are difficult to block its malignant transformation due to compensatory drug resistance.

[0005] Therefore, there is an urgent need to find drugs that can effectively block the transformation of chronic gastritis into cancer in order to achieve the goal of reducing the incidence of gastric cancer.

[0006] Chronic atrophic gastritis (CAG) is listed by the World Health Organization as a precancerous condition for gastric cancer. Long-term inflammation of the gastric mucosa leads to pathological changes such as glandular atrophy, intestinal metaplasia, and dysplasia, which are important foundations for the development of gastric cancer.

[0007] Chronic atrophic gastritis is a chronic digestive system disease characterized by atrophy of the gastric mucosal epithelium and glands, a decrease in their number, thinning of the gastric mucosa, thickening of the muscularis mucosae, or intestinal metaplasia or dysplasia. It often manifests as dull pain, bloating, belching, loss of appetite, or weight loss and anemia, and is nonspecific.

[0008] Applying the concept of "prevention before disease" in traditional Chinese medicine, and carrying out comprehensive management and prevention, is an effective strategy for preventing and treating the transformation of chronic gastritis into cancer. Developing effective drugs that can effectively prevent and treat the transformation of chronic gastritis into cancer is an urgent clinical need.

[0009] Combining the concept of preventive treatment in traditional Chinese medicine with modern biological techniques and shifting the focus of diagnosis and treatment earlier can potentially prevent the transformation of chronic gastritis into cancer, thereby ultimately reducing the incidence of gastric cancer. This has significant clinical and social value.

[0010] The concept of "prevention is better than cure" is of great significance in reducing the incidence of gastric cancer. It shifts the focus from "treatment-oriented to prevention-oriented" to proactive intervention, further moving the treatment focus to prevention, and has significant social value and meaning. Under the guidance of the concept of preventing disease progression, Academician Wang Qi, a master of traditional Chinese medicine, developed a representative formula that can block the transformation of chronic gastritis into cancer, based on key pathogenesis and key symptoms. This formula has achieved good clinical efficacy, providing a new and effective treatment for further achieving "early treatment" on top of the current "early diagnosis" and "early screening," thereby reducing the incidence of gastric cancer.

[0011] Existing reports on the treatment of gastritis with traditional Chinese medicine: A combination of Astragalus membranaceus, Curcuma zedoaria, Typha pollen, and Taraxacum mongolicum for the treatment of gastritis: CN104825997A (application number 201510197464.0) discloses a traditional Chinese medicine for treating chronic atrophic gastritis, the weight parts of the raw materials are as follows: Astragalus membranaceus 10-15, Curcuma zedoaria 5-6, Lilium brownii 2-4, Amomum villosum 6-8, Typha pollen 4-5, Dracaena cochinchinensis 2-4, Sargentodoxa cuneata 1-3, Taraxacum mongolicum 5-7, Scutellaria barbata 4-5, Angelica sinensis 7-8, Ligusticum chuanxiong 4-5, Corydalis yanhusuo 2-4, Lindera strychnifolia 6-10, Arctium lappa 3-5, Pinellia ternata 2-4, Polygonum multiflorum 5-7, Amomum villosum 5-6, Polygonatum sibiricum 2-4, Alpinia oxyphylla 10-15, Atractylodes macrocephala 5-8, Smilax china vine 2-4, and Aristolochia debilis 1-3. While this publicly disclosed patent prescription also involves herbs such as Astragalus membranaceus, Curcuma zedoaria, Typha pollen, and Taraxacum mongolicum, its overall formula consists of 22 herbs, a large number that is detrimental to the quality control of the finished drug. Its efficacy focuses on strengthening the spleen and replenishing qi, harmonizing the liver and spleen, regulating qi and resolving dampness, and promoting blood circulation and relieving pain, primarily targeting symptoms such as abdominal distension, pain, and heartburn. The aforementioned publicly disclosed patent prescription contains a large number of herbs, and its technical focus leans towards symptomatic qi regulation, pain relief, and spleen strengthening and dampness resolution, lacking sufficient coverage of key pathological processes in the inflammatory-cancer transformation process, such as gastric mucosal atrophy, intestinal metaplasia, and dysplasia. A combination of Magnolia officinalis, Curcuma zedoaria, chicken gizzard lining, dandelion, Hedyotis diffusa, and Astragalus membranaceus for the treatment of chronic gastritis: CN104288745A (application number 201410598022.2) discloses a traditional Chinese medicine for treating chronic gastritis, the composition of which is: Magnolia officinalis 5-15g, Poria cocos 5-15g, Sparganium stoloniferum 5-15g, Curcuma zedoaria 5-15g, Trogopterus xanthipes 5-15g, Scutellaria baicalensis 5-15g, Gardenia jasminoides 5-15g, Curcuma longa 5-15g, etc. The prescription includes: 5-15g of abdominal peel, 5-15g of Amomum villosum, 5-15g of chicken gizzard lining, 5-15g of Aucklandia lappa, 10-20g of Pinellia ternata, 10-20g of Codonopsis pilosula, 10-20g of Taraxacum mongolicum, 10-20g of Paeonia lactiflora, 10-20g of Trichosanthes kirilowii, 10-20g of Citrus aurantium, 10-20g of Cyperus rotundus, 10-20g of Corydalis yanhusuo, 10-20g of Angelica sinensis, 10-20g of Hedyotis diffusa, 15-25g of Astragalus membranaceus, 3-6g of Citrus medica, and 3-6 slices of fresh ginger. This prescription is indicated for general chronic gastritis. The instructions state that the main effects are improvement of symptoms such as upper abdominal distension, belching, acid reflux, loss of appetite, and stomach pain. However, it lacks sufficient description of the pathological changes associated with chronic atrophic gastritis, such as glandular atrophy, intestinal metaplasia, and dysplasia.

[0012] A combination of Astragalus membranaceus, Curcuma zedoaria, Hedyotis diffusa, and oyster shell for the treatment of gastritis: CN107184917A (application number 201710629345.7) discloses a traditional Chinese medicine composition for treating chronic atrophic gastritis and its application. The composition of the traditional Chinese medicine is as follows: 6-12 parts of raw Astragalus membranaceus, 6-12 parts of stir-fried Atractylodes macrocephala, 6-12 parts of Poria cocos, 6-12 parts of processed Pinellia ternata, 3-9 parts of Bupleurum chinense, 6-12 parts of Curcuma zedoaria, 9-15 parts of Curcuma longa, 6-12 parts of processed hedgehog skin, 10-20 parts of Lysimachia christinae, 9-15 parts of stir-fried Paeonia lactiflora, 1-5 parts of Coptis chinensis, 0.5-2 parts of Evodia rutaecarpa, 20-40 parts of Hedyotis diffusa, and 10-20 parts of raw oyster shell. The pathogenesis of this prescription is mainly based on "phlegm, deficiency, and blood stasis". The treatment focuses on strengthening the spleen and eliminating phlegm, promoting qi circulation and removing blood stasis, and regulating both cold and heat. The indication is limited to spleen deficiency with phlegm and blood stasis.

[0013] A combination of Astragalus membranaceus, Dendrobium nobile, Curcuma zedoaria, and Taraxacum mongolicum for the treatment of gastritis: CN108743878A (application number 201810931884.0) A traditional Chinese medicine pill for treating chronic atrophic gastritis, made from the following raw materials in parts by weight: Astragalus membranaceus 295-305, Codonopsis pilosula 195-205, Rehmannia glutinosa 95-105, Dendrobium nobile 95-105, Prunus mume 95-105, Schisandra chinensis 55-65, Panax notoginseng 55-65, Curcuma zedoaria 45 -55, Salvia miltiorrhiza 95-105, Scutellaria barbata 95-105, Taraxacum mongolicum 95-105, Bupleurum chinense 95-105, Perilla frutescens 145-155, Coix lacryma-jobi 195-205, Amomum villosum 95-105, Magnolia officinalis 95-105, Pinellia ternata 95-105, Poria cocos 145-155, Hordeum vulgare 145-155, Crataegus pinnatifida 145-155, Massa fermentata 145-155, Mica 295-305, Glycyrrhiza uralensis 95-105. The clinical evaluation of this prescription involved symptom scores, gastroscopy improvement, and overall effective rate. However, this prescription contains many ingredients, addressing multiple aspects such as tonifying qi and nourishing yin, promoting blood circulation and removing blood stasis, clearing heat and detoxifying, soothing the liver and regulating qi, and resolving dampness and promoting digestion. The prescription has a wide coverage, and the technical focus is relatively dispersed.

[0014] A combination of Astragalus membranaceus and Fritillaria cirrhosa for the treatment of gastritis: CN1189366A (application number 97108419.X) discloses a gastritis pill containing the following ingredients: Astragalus membranaceus 20-30g, Codonopsis pilosula 7-15g, stir-fried Paeonia lactiflora 20-30g, Glycyrrhiza uralensis 5-7g, Taraxacum mongolicum 15-20g, vinegar-fried Corydalis yanhusuo 7-10g, Aucklandia lappa 5-7g, stir-fried Melia toosendan 7-15g, Amomum villosum 7-10g, Coptis chinensis 5-7g, Fritillaria cirrhosa 7-10g, stir-fried Scutellaria baicalensis 7-10g, ginger-processed Pinellia ternata 5-7g, Salvia miltiorrhiza 10-15g, Crataegus pinnatifida 20-30g, Zingiber officinale 5-7g, Polygonatum odoratum 7-10g, and Dendrobium nobile 7-10g. This prescription is designed to treat gastritis and peptic ulcers. Its scope of application covers diseases such as gastritis, gastric and duodenal ulcers. The overall treatment method focuses on strengthening the spleen and replenishing qi, clearing heat and detoxifying, regulating qi and relieving pain, and promoting digestion and harmonizing the stomach. It is mainly used to control symptoms such as stomach pain, bloating, belching, and acid reflux. The focus is not on the pathological reversal of precancerous lesions in chronic atrophic gastritis.

[0015] In summary, most of the existing publicly available prescriptions either have broad indications, contain many ingredients, have a diversified formulation, or primarily focus on symptom improvement.

[0016] Chronic gastritis is primarily characterized by chronic inflammation of the gastric mucosa, with the glandular structure usually remaining intact. Clinically, it often manifests as upper abdominal pain, bloating, acid reflux, and belching. Traditional Chinese medicine commonly identifies patterns such as liver-stomach disharmony, spleen-stomach damp-heat, and spleen-stomach weakness. Treatment focuses on regulating qi and harmonizing the stomach, soothing the liver and strengthening the spleen, and clearing heat and dampness, with an emphasis on controlling inflammation and improving symptoms. Chronic atrophic gastritis, on the other hand, is characterized by a reduction in the intrinsic glands of the gastric mucosa and thinning of the mucosa. It may be accompanied by precancerous lesions such as intestinal metaplasia and dysplasia. The pathogenesis is often a case of deficiency in the root and excess in the branch, with spleen-stomach weakness and stomach yin deficiency as the underlying cause, accompanied by factors such as qi stagnation, blood stasis, phlegm accumulation, and toxin accumulation. The treatment goal is not only to relieve symptoms but also to improve or delay pathological changes such as atrophy, intestinal metaplasia, and dysplasia.

[0017] Existing traditional Chinese medicine formulas for treating gastritis or chronic atrophic gastritis mostly focus on symptom improvement, or primarily employ methods such as strengthening the spleen and stomach, regulating qi and relieving pain, promoting digestion and resolving stagnation, clearing heat and detoxifying, and promoting blood circulation and removing blood stasis. Even when nodule-dispersing drugs are involved, they are mostly used as auxiliary ingredients, and rarely involve systematic formulations addressing the mutual accumulation of blood stasis and toxins and malnourishment of the gastric collaterals in the precancerous stage of gastric disease. This invention does not follow the general approach of strengthening the spleen and regulating qi, clearing heat and resolving dampness, or promoting blood circulation and relieving pain for gastritis. Instead, it targets the inflammation-cancer transformation process of chronic atrophic gastritis, using "deficiency, damage, blood stasis, and toxins" as the core pathogenesis, and constructs a compound formulation system that regulates qi and blood circulation, detoxifies and disperses nodules. Summary of the Invention

[0018] The purpose of this invention is to provide a traditional Chinese medicine composition for treating chronic atrophic gastritis and its preparation method.

[0019] To achieve the above objectives, the present invention provides the following solution: In a first aspect, the present invention provides a traditional Chinese medicine composition for treating chronic atrophic gastritis, comprising the following raw materials in parts by weight: Astragalus membranaceus 9-30 parts, Curcuma zedoaria (processed with vinegar) 6-9 parts, Taraxacum mongolicum 10-15 parts, Typha pollen 5-10 parts, Dendrobium nobile 6-12 parts, Fritillaria cirrhosa 5-10 parts, Hedyotis diffusa 6-30 parts, Ostrea gigas 9-30 parts, stir-fried chicken gizzard lining 3-10 parts, and Magnolia officinalis 3-10 parts.

[0020] As the preferred embodiment, the traditional Chinese medicine composition contains the following raw materials in parts by weight: 15 parts Astragalus membranaceus, 9 parts Curcuma zedoaria (processed with vinegar), 15 parts Taraxacum mongolicum, 10 parts Typha pollen, 9 parts Dendrobium nobile, 6 parts Fritillaria cirrhosa, 20 parts Hedyotis diffusa, 20 parts Ostrea gigas, 9 parts stir-fried chicken gizzard lining, and 9 parts Magnolia officinalis.

[0021] Furthermore, the traditional Chinese medicine composition may be a decoction or granules. It is understood that any dosage form of the traditional Chinese medicine composition made from the above-mentioned raw materials is within the scope of protection of this invention.

[0022] Secondly, the present invention provides a method for preparing the traditional Chinese medicine composition for treating chronic atrophic gastritis as described in any of the above claims, by water extraction or decoction.

[0023] The specific steps include the following: weigh each ingredient according to the ratio, soak it in water and then decoct it for 20 to 30 minutes. Decoction is repeated 2 to 3 times to obtain the final product. Alternatively, the following steps may be included: weigh each ingredient according to the formula, add 5 to 15 times the amount of water and decoct for 0.5 to 1.5 hours, collect the decoction, filter, and concentrate until dry.

[0024] A third object of the present invention is to provide the use of the above composition in the preparation of a medicament for the prevention and treatment of chronic atrophic gastritis.

[0025] The drug is composed of a traditional Chinese medicine composition and a pharmaceutically acceptable carrier.

[0026] The drug is a conventional preparation, such as a tablet, capsule, or granule.

[0027] The pharmaceutically acceptable carrier is one or more of the following: diluent, binder, disintegrant, lubricant, or glidant.

[0028] Compared with the prior art, the present invention has the following beneficial effects: 1. Solution of the formula: 1) Using Astragalus membranaceus and Curcuma zedoaria (processed with vinegar) as the principal herbs: Astragalus has a sweet taste and slightly warm properties. It tonifies qi and raises yang, and is especially good at tonifying the qi of the spleen and stomach. It can also help to expel toxins and pus. Vinegar-processed turmeric has a pungent and bitter taste, and is warm in nature. It can break up blood stasis, promote qi circulation, eliminate stagnation, and relieve pain.

[0029] When used together, Astragalus membranaceus (Huangqi) can enhance the blood-activating power of Curcuma zedoaria (Ezhu) while preventing Curcuma zedoaria from depleting the body's vital energy, ensuring that the attack does not harm the body's vital energy and the tonification does not cause stagnation. In addition, Astragalus membranaceus is sweet and warm, with a gentle lifting effect, while Curcuma zedoaria is pungent and dispersing, with a strong effect. The combination of the two can also achieve a balance between strength and gentleness, allowing the ascending and descending functions to complement each other and the elimination and tonification to be orderly.

[0030] 2) Dandelion, cattail pollen, dendrobium, fritillaria cirrhosa, and oldenlandia diffusa are used as auxiliary herbs: Dandelion is bitter and sweet in taste, and cold in nature. It clears heat and detoxifies, reduces swelling and dissipates nodules. Fritillaria cirrhosa is bitter in taste, and slightly cold in nature. It detoxifies, resolves phlegm, reduces swelling and dissipates nodules. Hedyotis diffusa is bitter and sweet in taste, and cool in nature. It mainly detoxifies, reduces carbuncles, and dissipates nodules. The three herbs work together to detoxify and dissipate nodules, while also resolving phlegm. Combined with the principal herb Astragalus membranaceus, they work synergistically, with one clearing and one tonifying, one attacking and one defending, complementing each other.

[0031] Cattail pollen, sweet in taste and neutral in nature, can promote blood circulation and remove blood stasis. When used together with Fritillaria cirrhosa, it can help the principal herb Curcuma zedoaria to break up blood stasis, so that blood vessels can be unblocked and stasis can be eliminated.

[0032] Dendrobium is sweet in taste and slightly cold in nature. It benefits the stomach and promotes the production of body fluids, nourishes yin and clears heat. When combined with Astragalus membranaceus, the two herbs, one yang and one yin, one warm and one cold, help to transform body fluids and attach qi, resulting in remarkable effects of replenishing qi and promoting the production of body fluids.

[0033] In addition, oyster shell, stir-fried chicken gizzard lining, and magnolia bark are used as adjuvant herbs. Oyster shell is salty and slightly cold in nature, nourishing yin and softening hardness and dissipating nodules. When combined with other herbs, it enhances the detoxifying and nodule-dissipating effects. Magnolia bark and stir-fried chicken gizzard lining both enter the spleen and stomach meridians, resolving phlegm, regulating qi, strengthening the spleen, and eliminating stagnation. As an adjuvant, astragalus root helps to regulate the ascending and descending of qi in the spleen and stomach, thus regulating qi and providing an outlet for pathogenic factors.

[0034] The formula harmonizes Qi and blood, combining tonification and purgation, thus promoting the balance of Qi and blood, supporting the body's resistance and eliminating pathogens, achieving the combined effects of regulating Qi and blood, detoxifying and dispersing stagnation.

[0035] 2. This invention addresses the pathogenesis of chronic atrophic gastritis in its precancerous stage, characterized by the coexistence of "deficiency, damage, stasis, and toxicity." Specifically, it combines Typha pollen, Dendrobium nobile, and Fritillaria cirrhosa for intervention at this stage. Typha pollen invigorates blood circulation, removes blood stasis, and unblocks stomach collaterals, addressing the effects of prolonged illness affecting the collaterals and causing blood stasis. Dendrobium nobile nourishes the stomach, generates fluids, and repairs yin, addressing stomach yin deficiency, glandular atrophy, and mucosal malnutrition. Fritillaria cirrhosa detoxifies, resolves phlegm, and disperses nodules, addressing the accumulation of phlegm and toxins, the mutual binding of blood stasis and toxins, and the risk of disease progression. The combined use of these three herbs forms a complex intervention pathway of "invigorating blood—nourishing yin—dispersing nodules," ensuring their combined effects target the pathological changes.

[0036] Furthermore, the combination of Fritillaria cirrhosa and oyster shell for dispersing nodules has been more commonly used in diseases such as tumors and breast nodules. Although there are nodule-dispersing drugs in existing prescriptions related to gastritis, it is rare to see the complete combination of the two for the intervention of precancerous lesions of the stomach. This invention further combines Fritillaria cirrhosa, oyster shell, Curcuma zedoaria (processed with vinegar), and Magnolia officinalis. The combination of oyster shell and Fritillaria cirrhosa can enhance the effects of resolving phlegm, dispersing nodules, softening hard masses, and eliminating masses; the combination of Curcuma zedoaria (processed with vinegar) and Typha pollen can enhance the effects of promoting blood circulation, clearing the meridians, removing blood stasis, and eliminating accumulations; the combination of Magnolia officinalis and Dendrobium nobile can nourish and regulate the flow of qi, addressing both stomach yin deficiency, mucosal malnourishment, qi stagnation, and stomach disharmony.

[0037] The above-mentioned formulation distinguishes this invention from gastritis prescriptions that mainly target symptom relief or general inflammation control, demonstrating the advantages of the formulation in actively intervening from the precancerous stage of gastric disease and preventing the transformation of chronic atrophic gastritis into cancer.

[0038] 3. In terms of effectiveness: (1) The effects of the present invention were investigated by constructing a precancerous cell model of gastric cancer induced by MNNG. The results showed that the traditional Chinese medicine composition of the present invention has a certain therapeutic effect on chronic atrophic gastritis, specifically by promoting apoptosis of abnormally proliferating cells and improving malignant changes such as cell stemness and epithelial-mesenchymal transition.

[0039] (2) The traditional Chinese medicine composition of the present invention can effectively improve the pathological changes of gastric mucosa and gastrointestinal symptoms in patients with chronic atrophic gastritis, prevent the decline rate of gastric mucosal pathological score in patients with chronic atrophic gastritis by 79.17%, and improve symptoms by 71.79%. Attached Figure Description

[0040] Figure 1 The endoscopic findings and pathological findings of the gastric mucosa before (top row) and after (bottom row) treatment in a typical clinical case in Example 1 of this invention. Detailed Implementation

[0041] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification.

[0042] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0043] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0044] Composition of Example 1, Comparative Example 1, and Comparative Example 2: See Table 1 Table 1: Drug composition of examples and comparative examples (unit: g)

[0045] Preparation Example 1: Preparation of a Traditional Chinese Medicine Composition for Treating Chronic Atrophic Gastritis According to the formula of Example 1, weigh and mix the above raw materials, add 10 times the amount of water by weight, extract for 1 hour, repeat the above decoction process twice, extract a total of 3 times, filter, mix the obtained medicinal juice to obtain the traditional Chinese medicine composition (which can be taken directly).

[0046] Preparation Example 2: Preparation of Traditional Chinese Medicine Composition Granules for Treating Chronic Atrophic Gastritis According to the formula of Example 1, each raw material was weighed and subjected to water extraction, that is, by weight, 10 times the amount of water was used for extraction for 1 hour, the extraction was repeated 3 times, filtered, and concentrated under reduced pressure at 60°C to a density of 1.12~1.13 to a thick paste, and then the dry extract was prepared. Then, each component was converted to the weight of raw materials according to the extract and mixed according to the proportions in Example 1.

[0047] Preparation Example 3: Preparation of granules of a traditional Chinese medicine composition for treating chronic atrophic gastritis According to the formula of Example 1, the above raw materials were weighed and mixed, and extracted with 10 times the amount of water by weight for 1 hour. The extraction was repeated 3 times. The mixture was filtered and concentrated under reduced pressure at 60°C to a density of 1.12~1.13 to form a thick paste. The mixture was then prepared into a dry extract and mixed with dextrin at a ratio of 1:1~3. Ethanol (concentration ≥85%) was then used as a wetting agent, granulated, and sieved to obtain granules.

[0048] Experiment Example 1: Investigating the efficacy of a traditional Chinese medicine composition in treating chronic atrophic gastritis. 1. Research Methods (1) Preparation of drug-containing serum Forty-two male Wistar rats were selected and housed in a standardized clean animal facility, fed with standard feed, and given free access to water. After one week of acclimatization, the rats were randomly divided into seven groups using a random number table method. Blank serum, low-dose drug-containing serum (Example 1), medium-dose drug-containing serum (Example 1), high-dose drug-containing serum (Example 1), drug-containing serum (Comparative Example 1), drug-containing serum (Comparative Example 2), and folic acid-containing serum were prepared. The drug solution was prepared according to the "Equivalent Dose Ratio Table Based on Human and Animal Body Surface Area." Using an adult body weight of 60 kg and a conversion factor of 6.3 between rat and human body surface area, the gavage volume was 0.5 ml / 100 g. Specific gavage dosages are shown in Table 2. Gavage was performed continuously for 7 days.

[0049] One hour after the last administration, blood was collected from the abdominal aorta under isoflurane anesthesia in negative pressure blood collection tubes. After standing for 1 hour, the serum was separated by centrifugation at 3000 rpm for 10 minutes. The serum was inactivated by water bath at 56 ℃ for 30 minutes, filtered through a 0.22 μm filter, and aliquoted into sterile 1.5 ml EP tubes and stored at -80 ℃ for later use.

[0050] Table 2: Relationship between cell experiment grouping and serum preparation

[0051] (2) Cell model construction and processing GES-1 cells in the logarithmic growth phase were harvested, digested, centrifuged, and counted. 2 × 10⁶ cells were collected. 5 Cells were seeded in 10cm culture dishes, and 8mL of DMEM complete medium was added. The dishes were incubated overnight at 37℃ with 5% CO2. The next day, the original culture medium was discarded, and 8mL of DMEM complete medium containing 20μM, 40μM, and 80μM MNNG were added respectively. After 24 hours of incubation in the dark, the DMEM complete medium was replaced again. After approximately 8 days, a large number of cells were observed to float and die. When the remaining cells reached 80% confluence in about 2 weeks, they were routinely digested and passaged. The cells were divided into 8 groups: normal group, model group, low-dose group (Example 1), medium-dose group (Example 1), high-dose group (Example 1), comparative example 1, comparative example 2, and positive control group. Serum diluted with DMEM complete medium at a volume fraction of 10% was added to the cells in the logarithmic growth phase (see Table 2 for details). Cells were extracted after 12 and 24 hours for analysis.

[0052] (3) Observation indicators Cell viability, expression levels of apoptosis-related proteins, expression levels of stem cell-related proteins, and expression levels of epithelial-mesenchymal transition-related proteins.

[0053] (4) Statistical methods Statistical analysis was performed using SPSS 23.0 software. Experimental data are expressed as mean ± standard deviation. For comparisons among multiple samples, data conforming to normal distribution and homogeneity of variance were analyzed using ANOVA, and pairwise comparisons were performed using Tukey's post-hoc test. P <0.05 indicates a statistically significant difference.

[0054] 2. Research Results (1) Changes in cell viability: As shown in Table 3, compared with the model group, Example 1 reduced cell viability in a dose-dependent manner, suggesting that the herbal composition of this invention can significantly inhibit the abnormal proliferation of precancerous gastric cells. The medium-dose and high-dose groups in Example 1 were more effective than Comparative Examples 1 and 2 and the folic acid control group, indicating that the complete formulation of this invention is superior to the folic acid control group in inhibiting the abnormal proliferation of precancerous gastric cells. The absence of oyster shell or turmeric weakened the inhibitory effect of the prescription on the proliferation of precancerous gastric cells. The herbal composition of this invention can effectively reduce the viability of precancerous gastric cells, and its complete formulation has a good overall intervention advantage.

[0055] Table 3: Changes in cell viability

[0056] Note: Compared to the model group, ** P <0.01, *** P <0.001; compared with the dosage group in Example 1, # P <0.05, ### P <0.001; compared with the high-dose group in Example 1, △△△ P <0.001.

[0057] (2) Changes in the expression of proteins associated with malignant cell phenotypes As shown in Table 4, 24 hours after serum intervention, compared with the model group, Example 1 showed increased expression of the pro-apoptotic protein BAX and decreased expression of the anti-apoptotic protein Bcl-2 in a dose-dependent manner, suggesting that the herbal composition of this invention can promote apoptosis of precancerous gastric cells. Comparative Examples 1 and 2, while having some regulatory effect on BAX and Bcl-2 expression, were less effective than the medium-dose group and high-dose group of Example 1, suggesting that the prescription's effect on promoting apoptosis of abnormally proliferating cells was weakened after surgery without oyster or turmeric. The folic acid control group also improved the expression of apoptosis-related proteins, but overall it was not superior to the high-dose group of Example 1. The complete formulation of the herbal composition of this invention has a good pro-apoptotic effect.

[0058] Table 4: Expression levels of apoptosis-related proteins

[0059] Note: Compared to the model group, *** P <0.001; compared with the dosage group in Example 1, ### P <0.001; compared with the high-dose group in Example 1, △△△ P <0.001.

[0060] As shown in Table 5, compared with the model group, Example 1 reduced the expression of CD44 and OCT4 in a dose-dependent manner, suggesting that the herbal composition of the present invention can inhibit the abnormal expression of stem-related proteins in precancerous gastric lesions. Although Comparative Examples 1 and 2 showed some regulatory effect on CD44 and OCT4 expression, their overall effect was weaker than that of the medium-dose group and the high-dose group of Example 1, suggesting that the inhibitory effect on cell stemness was weakened after surgery without oyster or turmeric. The positive control group also reduced the expression of CD44 and OCT4, but its overall effect was not superior to that of the high-dose group of Example 1. The complete formulation of the herbal composition of the present invention has the advantage of effectively improving the abnormal expression of stem-related proteins in precancerous gastric lesions.

[0061] Table 5: Expression levels of cell stem-related proteins

[0062] Note: Compared to the model group, ** P <0.01, *** P <0.001; compared with the dosage group in Example 1, # P <0.05, ### P <0.001; compared with the high-dose group in Example 1, △△△ P <0.001.

[0063] As shown in Table 6, compared with the model group, Example 1 reduced N-Cadherin expression and increased E-Cadherin expression in a dose-dependent manner, suggesting that the herbal composition of this invention can improve the abnormal expression of proteins related to epithelial-mesenchymal transition (EMT) in precancerous gastric cells. Comparative Examples 1 and 2 also showed some regulatory effects, but were generally weaker than the medium-dose group and high-dose group of Example 1, suggesting that the lack of oyster or curcuma zedoaria after surgery weakens the effect of the prescription in improving EMT. The positive control group also improved the above indicators, but was not superior to the high-dose group of Example 1 overall. The herbal composition of this invention can effectively improve the abnormal expression of EMT-related proteins in precancerous gastric cells, and its complete formulation has a good overall intervention advantage.

[0064] Table 6: Expression levels of proteins related to epithelial-mesenchymal transition

[0065] Note: Compared to the model group, ** P <0.01, *** P <0.001; compared with the dosage group in Example 1,# P <0.05, ### P <0.001; compared with the high-dose group in Example 1, △ P <0.05, △△△ P <0.001.

[0066] The above results suggest that the herbal composition of the present invention can promote apoptosis of abnormally proliferating precancerous gastric cells, regulate cell stemness, improve epithelial-mesenchymal transition, and inhibit their malignant transformation.

[0067] Explanation: For chronic atrophic gastritis, especially those complicated with intestinal metaplasia or dysplasia, there is currently a lack of universally accepted specific drugs that can stably reverse the pathological changes in the gastric mucosa. Folic acid is often used clinically as an adjunct therapy for patients with chronic atrophic gastritis and precancerous lesions of the stomach. Previous relevant guidelines, expert consensus, and clinical studies also support the clinical application of folic acid, and several studies have used folic acid as a positive control drug. Therefore, this experiment selected folic acid as a positive control drug to evaluate the intervention effect of the herbal composition of this invention.

[0068] Experimental Example 2: Investigating the clinical efficacy of the herbal composition of the present invention in treating chronic atrophic gastritis. 1. Materials and Methods This prospective analysis investigated the efficacy of the herbal composition of this invention for 24 weeks in patients diagnosed with chronic atrophic gastritis with precancerous gastric mucosal conditions and lesions who visited three hospitals—the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine, and Dongfang Hospital of Beijing University of Traditional Chinese Medicine—between April and December 2024. This study was approved by the Ethics Committee of the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine (Approval No.: 2023-zj-33).

[0069] (1) Diagnostic criteria Patients diagnosed with precancerous mucosal conditions and precancerous lesions according to the criteria in the "Expert Consensus on Management Strategies for Precancerous Conditions and Precancerous Lesions of Gastric Mucosa in China (2020)".

[0070] (2) Inclusion criteria Enrolled patients must meet the diagnostic criteria for precancerous gastric conditions or precancerous lesions, be aged 18–70 years, regardless of gender, and have a negative Helicobacter pylori test (requiring at least one C13 or C14 breath test), voluntarily participate in this clinical trial, and provide informed consent by signing an informed consent form.

[0071] (3) Exclusion criteria Patients with concurrent peptic ulcers, pathologically confirmed high-grade intraepithelial neoplasia or suspected malignancy; those with severe digestive system diseases or a history of abdominal surgery; pregnant or lactating women; those with severe heart, lung, hematopoietic system, malignant tumors, or other serious systemic diseases; legally defined disabled patients; those with a history of long-term NSAID use or alcoholism; those with allergies or a history of allergies to multiple drugs; those who have participated in other drug clinical trials within the past 4 weeks, or used preparations such as Weifuchun or folic acid within the past 2 weeks; and those who are likely to be lost to follow-up.

[0072] (4) Intervention Program Patients meeting the inclusion criteria were enrolled sequentially according to their consultation order and treatment preferences. Treatment involved the use of granules of the herbal composition from Example 2, administered orally twice daily (morning and evening) with water for six consecutive months. During the study period, patients were prohibited from long-term concurrent use of any medications or external treatments that might have therapeutic effects on the disease.

[0073] (5) Observation indicators Clinical observation indicators include gastric mucosal pathological changes, endoscopic findings, and improvement in clinical symptoms. Specific methods are as follows: The endoscopist determines the extent of gastric mucosal dysplasia based on endoscopic findings, taking samples from the lesions. An evaluation method combining regional (location) and severity is used to assess gastric mucosal dysplasia. Samples from each site are placed in separate specimen boxes and sent for independent testing. Regions (locations): ① Antrum (lesser curvature, greater curvature); ② Angle; ③ Lesser curvature of body (upper, lower); ④ Pylorus; ⑤ Body (excluding the lesser curvature, upper, lower); ⑥ Fundus. The severity of the lesions is assessed according to the "Pathological Diagnostic Criteria for Chronic Gastritis," using a "visual simulation scoring method," categorized into four levels: none, mild, moderate, and severe (0, 1, 2, 3 points). A comprehensive evaluation of gastric mucosal atrophy, intestinal metaplasia, and dysplasia (intraepithelial neoplasia) in each region (location) is conducted. The score for each region is the sum of the severity of the areas contained within that region. Changes in the scores of each lesion and the total score before and after medication are evaluated. The formula is as follows: Total integral = Sum of actual regional integrals / Theoretical score range of actual region × 100.

[0074] The internationally recognized Patient-Reported Symptom Scale (MYMOP) was used to evaluate patients' clinical symptoms, and the changes in symptom scores before and after treatment were compared. A 50% improvement was defined as effective.

[0075] (6) Statistical analysis methods Statistical analysis was performed using SPSS 19.0 software. Quantitative data were described using minimum, maximum, median, mean, and standard deviation, and methods such as t-tests and rank-sum tests were employed. All statistical tests were two-tailed, and p < 0.05 was considered statistically significant.

[0076] 2. Research Results (1) Evaluation of pathological changes in gastric mucosa after treatment Clinical efficacy was evaluated based on the improvement of gastric mucosal pathological scores. After 24 weeks of treatment, the pathological score reduction rate was 79.17% for patients with chronic atrophic gastritis, 73.63% for patients with chronic atrophic gastritis and intestinal metaplasia, and 100% for patients with chronic atrophic gastritis and low-grade intraepithelial neoplasia.

[0077] (2) Evaluation of patient symptoms after treatment: see Tables 7 and 8 After treatment, the patient's symptoms such as abdominal distension, abdominal pain, and early satiety significantly improved, and symptoms such as acid reflux and belching also showed an improving trend. The improvement of clinical symptoms was evaluated using the MYMOP scale. The average score before treatment was 8.52±2.63 points, and the average score after 3 months of treatment was 6.35±2.16 points, a statistically significant difference. t =5.77, P <0.001); after 6 months of treatment, the average score was 4.42±1.52 points, with an effective rate of 71.79%, and the difference was statistically significant. t =12.20, P <0.001).

[0078] Table 7: MYMOP scores before and after treatment

[0079] Note: Compared with before treatment a P <0.001.

[0080] Table 8: Symptom scores before and after treatment

[0081] Note: Compared with before treatment a P <0.05, b P <0.001.

[0082] (3) Adverse reactions Safety indicators include: ① Physical examination: body temperature, respiration, pulse, blood pressure, etc.; ② Complete blood count, urinalysis, stool routine + OB, liver function, kidney function, electrocardiogram, urine HCG (female); ③ Adverse events: recorded promptly. No serious adverse reactions occurred in any patient treated with the herbal composition of this invention.

[0083] Experiment Example 3, Typical Case Analysis 1. The composition of this invention: Mr. Cao, male, 53 years old, presented with "intermittent abdominal pain, bloating, and decreased appetite for more than 5 years." Five years prior, the patient developed persistent, fixed-location upper abdominal pain without any obvious cause, which was more pronounced after meals and when experiencing emotional distress, accompanied by epigastric bloating, belching, and a gradual decrease in appetite. He intermittently took omeprazole and domperidone, with symptoms fluctuating in severity. On April 11, 2024, an electronic gastroscopy revealed active chronic atrophic gastritis, and the pathological diagnosis was moderate chronic atrophic gastritis with severe intestinal metaplasia, with a pathological score of atrophy 50 and intestinal metaplasia 75. His MYMOP score was 8. The patient was treated with the traditional Chinese medicine composition of this invention, with a fixed prescription, one dose per day, twice daily, orally, for 24 consecutive weeks. A follow-up electronic gastroscopy on October 31, 2024, revealed chronic atrophic gastritis. The pathological diagnosis was mild chronic atrophic gastritis with mild intestinal metaplasia. The pathological scores were atrophy 25 points (a decrease of 50% from before treatment) and intestinal metaplasia 16.67 points (a decrease of 78% from before treatment) (see...). Figure 1 The patient's MYMOP score was 2, a 67% decrease from pre-treatment levels. No adverse reactions were reported during treatment.

[0084] 2. Comparative Case 1: Mr. Shi, male, 63 years old, presented with "abdominal distension and abdominal pain for 3 years." Three years prior, he developed upper abdominal pain without any obvious cause, accompanied by abdominal distension and chest tightness. In May 2020, a gastroscopy revealed chronic atrophic gastritis with antral erosion and intestinal metaplasia. He usually ate quickly and had a good appetite. His tongue was pale red with a slightly yellow coating and teeth marks on the edges; his pulse was slightly slippery. Treatment focused on tonifying Qi, clearing heat, and eliminating carbuncles. He was given Comparative Case 1 treatment, one dose twice daily, orally, for two consecutive months. After treatment, the patient's upper abdominal pain and bloating improved, with no significant acid reflux or heartburn, and his appetite returned to normal. A follow-up gastroscopy in December 2022 revealed chronic atrophic gastritis with mild intestinal metaplasia.

[0085] The results suggest that the prescription in Comparative Example 1 has a certain effect on improving clinical symptoms such as epigastric pain and bloating, as well as gastric mucosal erosion. However, its prescription is not the complete formula of this invention and lacks some key ingredients. Its systemic intervention effect on pathological changes such as gastric mucosal atrophy and intestinal metaplasia is relatively limited.

[0086] 3. Comparative Case 2: Mr. Zhang, male, 48 years old, presented with a history of chronic atrophic gastritis discovered during a physical examination two years prior. In July 2022, a gastroscopy during a physical examination revealed chronic atrophic gastritis with moderate intestinal metaplasia, accompanied by postprandial epigastric fullness, abdominal distension, and recurring symptoms. He also experienced poor sleep and early awakening. His tongue was red at the edges, with a thin yellow coating, and his pulse was wiry. He was treated with Comparative Case 2, one dose twice daily, orally, for two consecutive months. After treatment, the patient's symptoms improved, abdominal distension lessened, and he experienced no abdominal pain or acid reflux. His appetite returned to normal. A follow-up gastroscopy in March 2024 confirmed chronic atrophic gastritis with moderate intestinal metaplasia.

[0087] The results suggest that the prescription in Comparative Example 2 focuses on clearing heat, nourishing yin, and regulating qi, which can improve symptoms related to qi stagnation such as abdominal distension and a feeling of blockage in the stomach. However, its ability to promote blood circulation, remove blood stasis, regulate qi, eliminate stagnation, and resolve masses is relatively insufficient. The degree of intestinal metaplasia was not significantly reversed after treatment, and its pathological improvement effect on chronic atrophic gastritis was limited.

[0088] 4. Conclusion: Both Comparative Example 1 and Comparative Example 2 can improve clinical symptoms such as epigastric pain, abdominal distension, and acid reflux in patients with chronic atrophic gastritis to some extent, but their effect on improving pathological changes such as intestinal metaplasia is limited.

[0089] Comparative Example 1 used *Sargentodoxa cuneata* instead of oyster shell, which has a stronger effect of clearing heat and detoxifying, promoting blood circulation and removing blood stasis, and relieving pain and swelling. It is suitable for improving inflammation and erosion, and therefore the clinical symptoms improved after treatment. However, the precancerous stage of chronic atrophic gastritis is characterized by the coexistence of "deficiency, damage, blood stasis, and toxins," and also involves pathological bases such as glandular atrophy, stomach yin deficiency, and phlegm-blood stasis. Example 1 uses oyster shell, combined with *Fritillaria cirrhosa* and *Dendrobium nobile*, which can enhance the effects of softening and dispersing nodules, nourishing yin and repairing. Cell experiments and typical case results both show that Example 1 has a better intervention effect than Comparative Example 1.

[0090] Comparative Example 2, which did not contain vinegar-processed Curcuma zedoaria, focused more on regulating qi and harmonizing the stomach, and could improve symptoms such as abdominal distension and a feeling of blockage in the stomach, but its ability to invigorate blood circulation, remove blood stasis, promote qi circulation, eliminate stagnation, and resolve masses was insufficient. Example 1, which retained vinegar-processed Curcuma zedoaria, could synergistically enhance the effects of invigorating blood circulation, removing blood stasis, and eliminating masses with Typha pollen, and could also form a combined attacking and tonifying effect with Astragalus membranaceus. At the same time, compared with Curcuma zedoaria alone, vinegar-processed Curcuma zedoaria was more conducive to regulating qi and blood circulation, removing blood stasis, and resolving masses, and its medicinal properties were relatively mild, with reduced pungent and dispersing properties, resulting in less gastrointestinal irritation. Cell experiments and typical case results further showed that Example 1 had a better overall effect than Comparative Example 2 in inhibiting the malignant changes of precancerous lesions of the stomach and improving the pathological state of the gastric mucosa.

[0091] In summary, the prescription of this invention, through its complete combination of invigorating qi and strengthening the body, promoting blood circulation and unblocking collaterals, nourishing yin and repairing, and detoxifying and dispersing nodules, can not only improve symptoms such as dull stomach pain and bloating, but also further target pathological changes such as atrophy, intestinal metaplasia, and dysplasia. The complete formulation of this invention better reflects the overall advantages of preventing and treating the inflammation-cancer transformation of chronic atrophic gastritis.

[0092] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions claimed by the present invention.

Claims

1. A traditional Chinese medicine composition for treating chronic atrophic gastritis, comprising the following raw materials in parts by weight: Astragalus membranaceus 9-30 parts, Curcuma zedoaria (processed with vinegar) 6-9 parts, Taraxacum mongolicum 10-15 parts, Typha pollen 5-10 parts, Dendrobium nobile 6-12 parts, Fritillaria cirrhosa 5-10 parts, Hedyotis diffusa 6-30 parts, Ostrea gigas 9-30 parts, stir-fried chicken gizzard lining 3-10 parts, and Magnolia officinalis 3-10 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition contains the following raw materials in parts by weight: 15 parts Astragalus membranaceus, 9 parts Curcuma zedoaria (processed with vinegar), 15 parts Taraxacum mongolicum, 10 parts Typha pollen, 9 parts Dendrobium nobile, 6 parts Fritillaria cirrhosa, 20 parts Hedyotis diffusa, 20 parts Ostrea gigas, 9 parts stir-fried chicken gizzard lining, and 9 parts Magnolia officinalis.

3. The method for preparing the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The preparation method is water extraction or water decoction.

4. The preparation method according to claim 3, characterized in that, The preparation method involves weighing each ingredient according to the proportion, soaking it in water, and then decocting it for 20-30 minutes, repeating the decoction 2-3 times.

5. The preparation method according to claim 3, characterized in that, The preparation method is as follows: weigh each component according to the ratio, add 5 to 15 times the amount of water and decoct for 0.5 to 1.5 hours, collect the decoction, filter, and concentrate until dry.

6. The use of the traditional Chinese medicine composition according to claim 1 or 2 in the preparation of a medicament for the prevention and treatment of chronic atrophic gastritis.

7. The application according to claim 6, characterized in that, The drug is composed of a traditional Chinese medicine composition and a pharmaceutically acceptable carrier.

8. The application according to claim 7, characterized in that, The drug is a conventional preparation.

9. The application according to claim 8, characterized in that, The drug is in the form of tablets, capsules, or granules.

10. The application according to claim 6, characterized in that, The application is intended to improve the pathological changes in the gastric mucosa of patients with chronic atrophic gastritis and reduce the risk of gastritis-cancer transformation.

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