A traditional Chinese medicine composition for treating chronic atrophic gastritis with low-grade intraepithelial neoplasia, and a preparation method and application thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating chronic atrophic gastritis with low-grade intra-epithelial neoplasia and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from raw materials including radix astragali 10-15 parts, rhizoma atractylodis macrocephalae 8-10 parts, poria cocos 10-15 parts, pericarpium citri reticulatae 8-10 parts, rhizoma pinelliae 5-8 parts, cyperus rotundus 12-15 parts, panax notoginseng 3-5 parts, radix curcumae 10-12 parts, root of actinidia 15-20 parts, herba hedyotis diffusae 15-20 parts and herba scorpiuridis 10-15 parts. The traditional Chinese medicine composition has good effects of improving gastric mucosa atrophy and low-grade intra-epithelial neoplasia, and has important application prospects for development of drugs for simple chronic atrophic gastritis and chronic atrophic gastritis combined with low-grade intra-epithelial neoplasia.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for treating chronic atrophic gastritis with low-grade intraepithelial neoplasia, its preparation method, and its application. Background Technology

[0002] Chronic atrophic gastritis is the most common precancerous lesion of the stomach. Recent clinical observations have found that severe gastric mucosal atrophy remains closely associated with gastric cancer even after Helicobacter pylori eradication. Multivariate analysis based on large samples also indicates that high-grade gastric mucosal lesions are an independent risk factor for gastric cancer. Chronic atrophic gastritis with low-grade intraepithelial neoplasia (LSIN) is a key pathological stage in the progression of chronic atrophic gastritis to gastric cancer. This stage refers to mild structural and cytological atypia of the gastric mucosal epithelial cells, which have not yet breached the basement membrane. It is a precancerous lesion of the stomach and has become one of the major chronic diseases threatening the health and quality of life of the Chinese population. Therefore, patients with chronic atrophic gastritis, especially those with metaplastic atrophy or higher-grade pathological changes (such as LSIN), are important targets for clinical monitoring and medical treatment. Modern medicine lacks effective methods for the recovery of gastric mucosal lesions in patients with chronic atrophic gastritis and low-grade intraepithelial neoplasia (H. pylori). Treatment often relies on the long process of self-repair of the gastric mucosa. Main treatments include eliminating causative factors, such as eradicating Helicobacter pylori, anti-bile reflux, and endoscopic therapy. However, these methods present challenges such as invasive procedures, recurrence, and patient anxiety. Therefore, there is an urgent need to find more effective drugs for patients with chronic atrophic gastritis and H. pylori. Digestive system diseases are areas where traditional Chinese medicine (TCM) excels, especially in understanding the pathogenesis of chronic atrophic gastritis and H. pylori. Personalized, dynamically followed TCM treatment can improve the level and rate of gastric mucosal repair, promoting improvement in the mucosal pathology of these patients. This would undoubtedly provide an effective and unique treatment approach for the population in my country with high rates of both H. pylori infection and gastric cancer, supplementing the treatment options for chronic atrophic gastritis and H. pylori, and holding significant importance for the prevention and treatment of gastric cancer. There is still much room for further research and development of traditional Chinese medicine compound formulas for the specific critical pathological stage of chronic atrophic gastritis with low-grade intraepithelial neoplasia. Summary of the Invention

[0003] The purpose of this invention is to provide a traditional Chinese medicine composition for treating chronic atrophic gastritis with low-grade intraepithelial neoplasia, its preparation method and application, which can be used for the treatment of chronic atrophic gastritis with low-grade intraepithelial neoplasia.

[0004] In a first aspect, the present invention provides a traditional Chinese medicine composition, made from raw materials comprising the following parts by weight:

[0005] Astragalus membranaceus 10-15 parts, Atractylodes macrocephala 8-10 parts, Poria cocos 10-15 parts, Citrus reticulata 8-10 parts, Pinellia ternata 5-8 parts, Cyperus rotundus 12-15 parts, Panax notoginseng 3-5 parts, Curcuma longa 10-12 parts, Actinidia chinensis root 15-20 parts, Scutellaria barbata 15-20 parts, Hedyotis diffusa 10-15 parts.

[0006] Although ancient Chinese medical texts do not record specific cases of chronic atrophic gastritis with low-grade intraepithelial neoplasia (LSIN), symptoms such as epigastric pain, heartburn, belching, and acid reflux fall under the categories of "stomach pain" and "abdominal distension" in traditional Chinese medicine. The pathogenesis of chronic atrophic gastritis is often a complex mixture of deficiency and excess, with spleen and stomach weakness as the root cause. Later stages progress to intestinal metaplasia and LSIN, often accompanied by phlegm, blood stasis, and toxins. The Six Gentlemen Decoction (Liu Jun Zi Tang), originating from *Medical Orthodox Transmission*, is composed of the Four Gentlemen Decoction (Si Jun Zi Tang) plus Pinellia ternata and Citrus reticulata peel. It has the effects of tonifying qi and strengthening the spleen, drying dampness and resolving phlegm, addressing both the root cause and the symptoms, and is a commonly used basic formula for treating chronic atrophic gastritis. For the stage of chronic atrophic gastritis with LSIN, the inventor, based on traditional Chinese medicine theory and long-term clinical experience, modified the Six Gentlemen Decoction to develop a Chinese herbal composition for treating chronic atrophic gastritis with LSIN, primarily using the principle of "strengthening the body's resistance and attacking toxins." This traditional Chinese medicine composition uses raw Astragalus membranaceus as the chief ingredient, replacing ginseng which has warming and drying properties, to achieve the effect of invigorating qi and promoting tissue regeneration. Atractylodes macrocephala and Poria cocos can dry dampness and eliminate turbidity, tonify the spleen and stomach. When combined with Astragalus membranaceus, they work together to strengthen the spleen and invigorate qi, nourishing the foundation of acquired constitution, and are thus the assistant ingredients. Tangerine peel is bitter and warm in nature, entering the spleen, stomach, and lung meridians. It has the functions of promoting qi circulation, relieving bloating, and drying dampness. Pinellia ternata is an essential medicine for drying dampness and resolving phlegm. When the two are used together, qi flows smoothly and phlegm is eliminated. Cyperus rotundus, Curcuma longa, and Panax notoginseng regulate qi, invigorate blood, and remove blood stasis. Scutellaria barbata, Actinidia chinensis root, and Hedyotis diffusa clear heat, resolve dampness, and detoxify, and are thus the adjuvant ingredients. The whole formula is used together to treat chronic atrophic gastritis with low-grade intraepithelial neoplasia with "phlegm," "blood stasis," and "toxins." It combines elimination and tonification, and treats both qi and blood, achieving the effect of "invigorating qi and strengthening the spleen, relieving stagnation and removing blood stasis." Long-term clinical practice and observation have found that this traditional Chinese medicine compound can significantly alleviate the clinical symptoms of patients with chronic atrophic gastritis accompanied by low-grade intraepithelial neoplasia, improve gastric mucosal atrophy, intestinal metaplasia, and low-grade intraepithelial neoplasia lesions, improve the quality of life of patients, and has good safety.

[0007] According to the present invention, the formulation of the traditional Chinese medicine composition can be adjusted according to the patient's TCM syndrome type and symptoms. Further, the traditional Chinese medicine composition is any one of the following: A1) The Chinese herbal composition also includes 6-10 parts of vinegar-processed Bupleurum chinense, 8-12 parts of Scutellaria baicalensis, and 12-18 parts of Curcuma zedoaria; specifically, this formula can be used when the patient is diagnosed with spleen and stomach deficiency syndrome and is accompanied by liver fire and blood stasis. A2) The Chinese medicine composition also includes 15-30 parts of calcined oyster shell and 10-20 parts of prunella vulgaris; specifically, when the patient has a bitter taste in the mouth, dry throat, occasional acid reflux, cough with yellow sticky phlegm, and the phlegm is easy to cough up, calcined oyster shell can be added to eliminate phlegm and remove blood stasis, neutralize acid and relieve pain, while prunella vulgaris clears liver fire, disperses nodules and removes blood stasis. A3) The Chinese medicine composition also includes 6-10 parts Platycodon grandiflorus and 6-10 parts Saposhnikovia divaricata; specifically, when the patient occasionally has a dry cough without phlegm and sleep is normal, Platycodon grandiflorus can be added to promote lung function and soothe the throat, and Saposhnikovia divaricata can be added to dispel wind and relieve pain. A4) The traditional Chinese medicine composition also includes 15-25 parts of coix seed and 10-15 parts of salvia miltiorrhiza; specifically, when the patient's tongue coating is white and slightly greasy and the pulse is still thin, coix seed can be added to enhance the spleen-strengthening and dampness-removing effects, so as to further improve the spleen and stomach's digestive function; salvia miltiorrhiza is added to strengthen the blood-activating and stasis-removing power, promote the circulation of qi and blood, and improve the state of blood stasis in the body; A5) The traditional Chinese medicine composition also includes 10-15 parts of prepared Polygala tenuifolia, 20-40 parts of Chaenomeles speciosa, 5-8 parts of Pheretima aspergillum, 8-12 parts of Cinnamomum cassia, 8-12 parts of Terminalia chebula and 20-40 parts of raw dragon bone; when the patient occasionally experiences weakness and discomfort in both lower limbs, which worsens on rainy days and affects sleep, and occasionally experiences dry mouth and throat, this composition can be further adjusted.

[0008] In one embodiment of the present invention, the traditional Chinese medicine composition is made from raw materials comprising the following parts by weight: Astragalus membranaceus 15 parts, Atractylodes macrocephala 10 parts, Poria cocos 10 parts, Citrus reticulata 10 parts, Pinellia ternata 5 parts, Cyperus rotundus 15 parts, Panax notoginseng 3 parts, Curcuma longa 12 parts, Actinidia chinensis root 15 parts, Scutellaria barbata 15 parts, Hedyotis diffusa 15 parts.

[0009] In one embodiment of the present invention, the traditional Chinese medicine composition is any one or a combination of the following: B1) The traditional Chinese medicine composition also includes 8 parts of vinegar-processed Bupleurum chinense, 10 parts of Scutellaria baicalensis tablets, and 15 parts of Curcuma zedoaria; B2) The traditional Chinese medicine composition also includes 20 parts of calcined oyster shell and 15 parts of prunella vulgaris; B3) The traditional Chinese medicine composition also includes 8 parts Platycodon grandiflorus and 8 parts Saposhnikovia divaricata; B4) The traditional Chinese medicine composition also includes 20 parts of coix seed and 15 parts of salvia miltiorrhiza; B5) The traditional Chinese medicine composition also includes 12 parts of prepared Polygala tenuifolia, 30 parts of Chaenomeles speciosa, 6 parts of Pheretima aspergillum, 10 parts of Cinnamomum cassia, 10 parts of Terminalia chebula and 30 parts of raw dragon bone.

[0010] In one embodiment of the present invention, the traditional Chinese medicine composition is a decoction.

[0011] Secondly, the present invention provides a method for preparing the traditional Chinese medicine composition, comprising the following steps: adding water to the raw materials for decoction, filtering, and obtaining the traditional Chinese medicine composition; preferably, the decoction is performed 2 to 3 times, and the decoctions are combined; the amount of water used for each decoction is 5 to 10 times the total mass of the raw materials; and the decoction time is 1 to 1.5 hours each time.

[0012] Thirdly, the present invention provides the use of the traditional Chinese medicine composition described in any one of the above-mentioned items or the traditional Chinese medicine composition prepared by the method described therein in any one of the following: C1) Prepare drugs for the prevention and / or treatment of chronic atrophic gastritis; C2) Prepare drugs for the prevention and / or treatment of precancerous lesions of the stomach; C3) Prepare drugs for the prevention and / or treatment of chronic atrophic gastritis with low-grade intraepithelial neoplasia; C4) Prepare a drug to improve gastric mucosal lesions, wherein the gastric mucosal lesions include one or more of the following: inflammation, atrophy, intestinal metaplasia, and low-grade intraepithelial neoplasia; C5) Prepare drugs for the prevention of gastric cancer.

[0013] In the above applications, the chronic atrophic gastritis refers to Helicobacter pylori-negative chronic atrophic gastritis, or gastric precancerous lesions such as low-grade intraepithelial neoplasia.

[0014] In the above applications, the drug is used to prevent or treat diseases diagnosed by Traditional Chinese Medicine (TCM) as spleen and stomach deficiency with phlegm and blood stasis; or, the drug is used to prevent or treat diseases diagnosed by TCM as spleen deficiency and blood stasis. These diseases include, but are not limited to, chronic atrophic gastritis, precancerous lesions of the stomach, chronic atrophic gastritis with low-grade intraepithelial neoplasia, or stomach cancer.

[0015] Fourthly, the present invention provides a medicine having any of the following functions, comprising the traditional Chinese medicine composition described in any of the above descriptions or the traditional Chinese medicine composition prepared by the method described above, and pharmaceutically acceptable excipients thereof; D1) Prevention and / or treatment of chronic atrophic gastritis; D2) Prevention and / or treatment of precancerous lesions of the stomach; D3) Prevention and / or treatment of chronic atrophic gastritis with low-grade intraepithelial neoplasia; D4) Prepare a drug to improve gastric mucosal lesions, wherein the gastric mucosal lesions include one or more of the following: inflammation, atrophy, intestinal metaplasia, and low-grade intraepithelial neoplasia; D5) Prevents stomach cancer.

[0016] The dosage forms of the aforementioned drugs include, but are not limited to, granules, oral liquids, tablets, capsules, and powders.

[0017] The present invention has the following beneficial effects: Clinical studies have found that the total effective rate of the herbal composition of this invention in treating gastric mucosal lesions is 82.29%, and the disappearance rate of low-grade intraepithelial neoplasia is 64.46%. It can significantly relieve symptoms such as abdominal distension / pain, preference for warmth / pressure in the stomach, constipation, heartburn, acid reflux, and bitter taste in the mouth, with a total effective rate of 86.46% in symptom improvement. The drug showed good safety during use.

[0018] The results of this invention show that the traditional Chinese medicine composition has a good effect on improving gastric mucosal atrophy and low-grade intraepithelial neoplasia. This indicates that the traditional Chinese medicine composition is a drug with great development potential for both simple chronic atrophic gastritis and chronic atrophic gastritis complicated with low-grade intraepithelial neoplasia. It can be directly used for the treatment of the corresponding diseases and the preparation of related drugs. Attached Figure Description

[0019] Figure 1 This is a gastroscopy photograph taken before treatment in Embodiment 3 of the present invention.

[0020] Figure 2 This is a gastroscopy image taken after treatment in Embodiment 3 of the present invention. Detailed Implementation

[0021] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0022] Unless otherwise specified, the methods used in the following embodiments are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following embodiments are commercially available.

[0023] The raw materials used in the following examples, namely Astragalus membranaceus, Atractylodes macrocephala, Poria cocos, Citrus reticulata peel, Pinellia ternata, Cyperus rotundus, Panax notoginseng, Curcuma longa, Actinidia chinensis root, Scutellaria barbata, and Hedyotis diffusa, are all medicinal materials listed in the Chinese Pharmacopoeia or the Chinese Medicine Processing Standards. After identification, all indicators meet the requirements.

[0024] Example 1: Preparation of a traditional Chinese medicine composition (decoction) The following herbal ingredients are prepared in the following proportions by weight: Astragalus membranaceus 15g, Atractylodes macrocephala 10g, Poria cocos 10g, Citrus reticulata peel 10g, Pinellia ternata 5g, Cyperus rotundus 15g, Panax notoginseng 3g, Curcuma longa 12g, Actinidia chinensis root 15g, Scutellaria barbata 15g, and Hedyotis diffusa 15g. These herbs are decocted twice with water, each time using 10 times the weight of the herbs. The first decoction is for 1.5 hours, and the second for 1 hour. The decoctions are combined, filtered, and the total volume of the two decoctions is 400ml. The concentration is equivalent to 0.30g / ml of the raw herbs (measured at 20℃). The dosage and administration are as follows: Oral administration, 200ml twice daily.

[0025] Example 2: The therapeutic effect of a traditional Chinese medicine composition on chronic atrophic gastritis with low-grade intraepithelial neoplasia. This study investigated patients with chronic atrophic gastritis (CAG) and low-grade intraepithelial neoplasia (LGIN) using a multicenter, prospective, randomized parallel controlled design. Evidence-based traditional Chinese medicine was used as a positive control. The LGIN regression rate was the primary efficacy endpoint, while gastric mucosal pathology score and clinical symptom score were secondary efficacy endpoints. The study evaluated the efficacy and safety of the traditional Chinese medicine composition and established a nationwide multicenter LGIN cohort. This provides scientific evidence for the translation and application of this compound and offers a reliable treatment plan for CAG.

[0026] I. Research Plan 1. Treatment subjects This study included patients with CAG combined with LGIN diagnosed since April 2022 at various centers (Peking University First Hospital, Dongfang Hospital of Beijing University of Chinese Medicine, and Shanxi Provincial Hospital of Traditional Chinese Medicine).

[0027] 2. Discharge Standards (1) Inclusion criteria ① Diagnosed with LGIN by endoscopy and gastric mucosal biopsy (refer to the Consensus Opinion on Chronic Gastritis in China (2017, Shanghai)); ② Negative carbon-13 or carbon-14 urea breath test; ③ Age 18-70 years, gender not limited; ④ Traditional Chinese medicine diagnosis of spleen and stomach deficiency and phlegm-blood stasis syndrome (refer to the Consensus Opinion on the Diagnosis and Treatment of Chronic Atrophic Gastritis by Integrated Traditional Chinese and Western Medicine (2017) of the Digestive System Diseases Professional Committee of the Chinese Association of Integrative Medicine).

[0028] Western medicine diagnostic criteria: Based on the "Chinese Consensus Opinion on Chronic Gastritis", the diagnosis is confirmed by gastroscopy and pathological biopsy as chronic atrophic gastritis with low-grade intraepithelial neoplasia.

[0029] Traditional Chinese Medicine (TCM) diagnostic criteria: Based on the "Consensus Opinion on the Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Chronic Atrophic Gastritis (2017)" and the guidelines for the management of precancerous lesions of the stomach, the syndrome is diagnosed as spleen and stomach deficiency with phlegm and blood stasis. Primary symptoms: ① epigastric fullness or dull pain; ② pale, thin, or granular nodular gastric mucosa. Secondary symptoms: ① poor appetite; ② fatigue; ③ purplish-dark tongue or petechiae, and a choppy pulse. A diagnosis can be made if two primary symptoms and two secondary symptoms are present.

[0030] (2) Exclusion criteria: ① History of gastric surgery or endoscopic treatment; ② Comorbid malignant tumor; ③ Acute exacerbation or worsening of chronic disease, or history of mental illness; ④ History of allergy to the research drug component; ⑤ Planning pregnancy, pregnant or breastfeeding woman.

[0031] 3. Intervention measures (1) Traditional Chinese medicine composition group: The traditional Chinese medicine composition of Example 1, 200ml twice a day.

[0032] The decoction was prepared by the research unit according to a standardized procedure.

[0033] (2) Moluodan Group: Moluodan 9g / bag (manufacturer: Handan Pharmaceutical Co., Ltd., specification: 1.84g per 16 pills), 16 pills (1 bag) each time, 3 times a day. Its drug composition is: lily bulb, poria cocos, scrophularia ningpoensis, lindera strychnifolia, alisma plantago-aquatica, ophiopogon japonicus, angelica sinensis, artemisia capillaris, corydalis yanhusuo (vinegar-processed), white peony root, dendrobium nobile, acorus tatarinowii, chuanxiong rhizome, chicken gizzard lining, notoginseng, atractylodes macrocephala (wheat bran-fried), sanguisorba officinalis, cattail pollen), 1 bag each time, 3 times a day, for 6 consecutive months.

[0034] Concomitant medication guidelines: During the intervention period, patients should not take any traditional Chinese medicine decoctions, proprietary Chinese medicines, endogenous mucosal protectants, or vitamin preparations for the treatment of CAG other than those specified in the study protocol. If dyspepsia symptoms that cannot be controlled by the study drugs occur during the intervention period, exogenous mucosal protectants, prokinetic agents, or acid suppressants may be used for a short period (not exceeding 2 consecutive weeks) under the guidance of researchers.

[0035] 4. Therapeutic Indicators (1) Main therapeutic indicators LGIN regression rate: Gastroscopy and gastric mucosal tissue pathological examination were performed within 3 months after the end of drug intervention to calculate the LGIN regression rate.

[0036] The definition of LGIN regression is: no LGIN was found in any of the biopsy tissue samples.

[0037] LGIN regression rate = (Number of patients whose LGIN regressed from baseline at enrollment / Number of patients treated) × 100%.

[0038] In this study, pathological tissue samples were obtained under narrow-band imaging high-definition magnification gastroscopy, and the samples should include at least three tissues: the gastric antrum, gastric body, and gastric angle. All pathological slides were sent to the lead unit and interpreted by gastroenterology pathologists in a blinded state.

[0039] (2) Secondary therapeutic indicators ① Gastric mucosal pathological score: According to the Sydney classification system for gastric mucosal lesions in the "Chinese Consensus Opinion on Chronic Gastritis" (2017) (Table 1), chronic inflammation, atrophy, intestinal metaplasia, and low-grade intraepithelial neoplasia were scored according to different degrees of severity, with 0, 1, 2, and 3 points respectively for none, mild, moderate, and severe. The overall gastric mucosal lesion score and the scores of each pathological condition were calculated.

[0040] ② Evaluation of treatment efficacy in gastric mucosal pathology Pathological efficacy evaluation criteria: Cured: Low-grade intraepithelial neoplasia disappears; Significantly effective: Low-grade intraepithelial neoplasia, intestinal metaplasia, or atrophy is reduced by 2 grades; Effective: Low-grade intraepithelial neoplasia, intestinal metaplasia, or atrophy is reduced by 1 grade; Ineffective: The above effective criteria are not met.

[0041] ③ Evaluation of the efficacy of TCM syndromes The TCM syndrome scores of patients before and after treatment were observed. The TCM syndrome score assessment was based on the "Consensus Opinion on the Diagnosis and Treatment of Chronic Atrophic Gastritis with Integrated Traditional Chinese and Western Medicine (2017)". The patients were scored on 2 main symptoms and 13 secondary symptoms. The main and secondary symptoms were divided into four levels: none, mild, moderate and severe. The main symptoms were scored as 0, 2, 4 and 6 points, and the secondary symptoms were scored as 0, 1, 2 and 3 points. See Table 1 for details.

[0042] Table 1. Traditional Chinese Medicine Syndrome Score Assessment Standards

[0043] ④ Criteria for Judging the Therapeutic Effect of Traditional Chinese Medicine Syndromes The efficacy of TCM syndromes was evaluated using the nimodipine method. The efficacy index = [(pre-treatment score)] [Post-treatment score / Pre-treatment score] × 100%. Cure: Symptoms and signs disappear or basically disappear, efficacy index ≥ 95%; Significant effect: Symptoms and signs significantly improve, 70% ≤ efficacy index < 95%; Effective: Symptoms and signs improve, 30% ≤ efficacy index < 70%; Ineffective: Symptoms and signs do not significantly improve, or even worsen, efficacy index < 30%.

[0044] (3) Safety indicators Adverse reaction incidence: Number of drug-related adverse reactions during the intervention period / Population analyzed for safety × = 100%.

[0045] Expected adverse drug reactions include: bitter taste in the mouth, nausea, diarrhea, loss of appetite, and other gastrointestinal discomfort.

[0046] 5. Standards for shedding and rejection (1) Dropout criteria: ① Loss to follow-up; ② Unbearable adverse drug reactions; ③ Serious adverse events; ④ Subjects voluntarily withdraw their informed consent; ⑤ Disease progression during the intervention, with the development of high-grade intraepithelial neoplasia or early gastric cancer; ⑥ Other circumstances determined by the investigator that affect the assessment of efficacy during the intervention.

[0047] The definition of serious adverse events: events that occur to subjects during the study, such as requiring hospitalization, prolonged hospitalization, disability, impact on work ability, life-threatening or death, or congenital malformation.

[0048] (2) Exclusion criteria: ① Medication adherence <80% or >120%; ② Violation of regulations on combined medication use.

[0049] 6. Randomization and Blinding (1) Randomization method: A central block randomization method was used, with medical statisticians generating random sequences using SAS software. Random numbers and corresponding subgroups were placed in opaque envelopes. After participants signed informed consent and were successfully screened, they opened the envelopes to obtain their subgrouping results and received the appropriate intervention.

[0050] (2) Blinding: The intervention protocol in this study was not blinded; patients and researchers administering the drug intervention were informed of the grouping results. Efficacy assessment was blinded, with the endoscopy operators and pathologists blinded. The relevant procedures were performed by researchers unaware of the patient's intervention method, and all pathological interpretations were conducted by pathologists from the lead institution under blinded conditions.

[0051] II. Results A total of 168 patients were included, of whom 112 received treatment with a decoction of a traditional Chinese medicine composition (TCM composition group) and 56 received treatment with Moluodan (control group). In the TCM composition group, 16 patients dropped out, 96 patients completed 6 months of treatment, and 96 patients completed endoscopic follow-up. In the control group, 8 patients were lost to follow-up, 48 patients completed 6 months of treatment, and 48 patients completed endoscopic follow-up.

[0052] 1. Basic information of patients who completed 6 months of treatment Ninety-six patients in the traditional Chinese medicine combination group completed six months of treatment, while 48 patients in the control group completed six months of treatment. There were no statistically significant differences between the two groups in terms of gender, disease duration, age, family history of gastric cancer, and history of smoking and alcohol consumption (P > 0.05), as shown in Table 2.

[0053] Table 2 Comparison of general situations between the two groups

[0054] 2. Comparison of LGIN fading rates The disappearance rate of low-grade intraepithelial neoplasia after treatment with the traditional Chinese medicine composition was 64.46%, which was higher than that of the control group (31.25%). The difference between the two groups was statistically significant (see Table 3).

[0055] Table 3. Evaluation indicators of treatment efficacy [n(%)]

[0056] 3. Comparison of pathological changes in the gastric mucosa 3.1 Comparison of gastric mucosal pathological scores before and after treatment in the two groups After treatment with the traditional Chinese medicine combination, the patients' gastric mucosal inflammation and intestinal metaplasia pathology scores were lower than before treatment. P >0.05), gastric mucosal atrophy, low-grade intraepithelial neoplasia, and total pathological score were all significantly lower than before treatment. P <0.05; In the control group, the scores for gastric mucosal inflammation, atrophy, intestinal metaplasia, low-grade intraepithelial neoplasia, and total pathological score were lower than before treatment, but the difference was not statistically significant. P >0.05). There was no statistically significant difference in gastric mucosal pathological scores between the two groups before treatment. P >0.05), after treatment, the differences between the two groups in gastric mucosal atrophy, low-grade intraepithelial neoplasia, and total pathological score were statistically significant. P <0.05), see Table 4.

[0057] Table 42 Comparison of gastric mucosal pathological scores before and after treatment in two groups (points, ±s)

[0058] Note: Compared to baseline, P <0.05 3.2 Comparison of the overall effective rate of improvement in gastric mucosal lesions between the two groups after treatment The total effective rate of the traditional Chinese medicine composition in improving gastric mucosal lesions was 82.29%, while the total effective rate of the control group was 43.75%. The difference between the two groups was statistically significant. P <0.05), see Table 5.

[0059] Table 5. Comparison of the overall effective rate of improvement in gastric mucosal lesions after treatment in 52 groups [n(%)]

[0060] Note: Compared with the Molodan group. P <0.05 4. Comparison of clinical symptom improvement 4.1 Comparison of TCM symptom scores before and after treatment in the two groups After treatment with the traditional Chinese medicine combination group, the scores of symptoms such as abdominal distension / dull pain, preference for warmth / pressure in the stomach, constipation, heartburn and acid reflux, and bitter taste in the mouth all decreased significantly compared with those before treatment (P<0.01). The scores of other symptoms did not decrease significantly compared with those before treatment. P >0.05); In the control group, the scores of defecation difficulties decreased significantly compared with those before treatment (P<0.01), while the scores of other symptoms did not decrease significantly compared with those before treatment (P>0.05). P >0.05). There was no statistically significant difference in symptom scores between the two groups before treatment. P >0.05), the scores of symptoms such as abdominal distension / dull pain, preference for warmth / pressure in the stomach, shortness of breath, stomach discomfort, heartburn and acid reflux were significantly improved after treatment with the traditional Chinese medicine combination compared to the control group. P <0.05), see Table 6.

[0061] Table 62 Comparison of symptom scores before and after treatment in two groups (points, ±s)

[0062] Note: Compared to baseline, P <0.05 4.2 Comparison of the overall effective rate of symptom relief between the two groups of traditional Chinese medicine The total effective rate of symptoms in the traditional Chinese medicine combination group was 86.46%, while the total effective rate in the control group was 47.92%, and the difference between the two groups was statistically significant. P <0.05), see Table 7.

[0063] Table 7. Comparison of the overall effective rate of symptom relief between the two groups using Traditional Chinese Medicine [n(%)]

[0064] Note: Compared with the Molodan group. P <0.05 5. Safety indicators No significant abnormalities were found in the liver and kidney function of the patients who underwent gastroscopy, and no adverse reactions were observed.

[0065] 6. Conclusion The traditional Chinese medicine composition effectively alleviates the clinical symptoms of patients with chronic atrophic gastritis accompanied by low-grade intraepithelial neoplasia (LDN), providing some relief for atrophy, intestinal metaplasia, and LDN lesions, with good safety. Its efficacy on gastric mucosal lesions is higher than that of the traditional Chinese medicine preparation Moluodan. This suggests that the traditional Chinese medicine composition is a feasible treatment option for chronic atrophic gastritis with LDN and is a drug with great development potential.

[0066] Example 3: A typical case of treating chronic atrophic gastritis with low-grade intraepithelial neoplasia using a traditional Chinese medicine composition. The patient is a 62-year-old male who first visited the hospital on October 17, 2023.

[0067] Chief complaint: Upper abdominal discomfort for 2 years, worsening in the past week. Two years ago, the patient developed upper abdominal discomfort without any obvious cause, including postprandial abdominal distension and occasional dull pain. One week ago, the symptoms worsened after eating ice cream, with significant dry mouth and bitter taste. Poor appetite, loose stools once a day, and normal sleep. Dark red tongue with teeth marks on the edges, tortuous sublingual veins, white and greasy tongue coating, and a thready and wiry pulse.

[0068] Past medical history: Diabetes for 22 years, currently managed with regular oral administration of dapagliflozin 10mg once daily (qd) to control blood sugar, which is well controlled; Hypertension for 2 years, currently managed with regular oral administration of amlodipine besylate 10mg once daily (qd) to control blood pressure, which fluctuates between 110-120 / 70-80 mmHg. Denies any other chronic illnesses or medication history, and denies any history of smoking or alcohol consumption.

[0069] Auxiliary examinations: Gastroscopy performed at Peking University First Hospital on August 11, 2023, showed chronic gastritis with erosion; pathological examination showed: (gastric angle) mild chronic gastritis, moderate intestinal metaplasia, moderate atrophy, and focal mild atypical hyperplasia of glands; (gastric body) mild chronic gastritis, activity level 1, moderate intestinal metaplasia, moderate atrophy, and focal mild to moderate atypical hyperplasia of glands (e.g., Figure 1 ).

[0070] Western medical diagnosis: 1. Low-grade gastric intraepithelial neoplasia; 2. Type 2 diabetes mellitus; 3. Hypertension. Traditional Chinese Medicine diagnosis: abdominal distension (spleen deficiency and blood stasis syndrome).

[0071] The initial diagnosis considered the patient's main symptoms to be spleen and stomach deficiency with blood stasis. Therefore, a combination of Chinese herbal medicines was prescribed: Astragalus membranaceus 15g, Atractylodes macrocephala 10g, Poria cocos 10g, Citrus reticulata peel 10g, Pinellia ternata 5g, Cyperus rotundus 15g, Panax notoginseng 3g, Curcuma longa 12g, Actinidia chinensis root 15g, Scutellaria barbata 15g, Hedyotis diffusa 15g, plus Bupleurum chinense (processed with vinegar) 8g, Scutellaria baicalensis slices 10g, and Curcuma zedoaria 15g. The decoction was prepared and taken twice a day, morning and evening, warm.

[0072] Since the initial consultation, the patient has intermittently visited the outpatient clinic to adjust the prescription. The main prescription of the Chinese herbal composition remains unchanged, but is modified according to the patient's symptoms.

[0073] On October 15, 2023, the patient returned for a follow-up visit, reporting that the dull pain in the upper abdomen had improved, but there was still a bitter taste in the mouth, dry throat, occasional acid reflux, and coughing up yellow sticky phlegm that was easy to expectorate. The prescription was adjusted to a combination of Chinese medicine ingredients with the addition of 20g of calcined oyster shell to eliminate phlegm, remove blood stasis, neutralize acid, and relieve pain, and 15g of Prunella vulgaris to clear liver fire, disperse nodules, and remove blood stasis. The prescription was decocted in water and taken twice a day, morning and evening, while warm.

[0074] On February 5, 2024, the patient's symptoms were significantly relieved after taking the medication. Recently, the patient has experienced occasional dry cough without phlegm. Bowel movements are once a day, formed, and sleep is normal. The prescription is a combination of traditional Chinese medicine herbs plus 8g of Platycodon grandiflorus to promote lung function and soothe the throat, and 8g of Saposhnikovia divaricata to dispel wind and relieve pain. The herbs are decocted in water and taken warm twice a day, morning and evening.

[0075] On March 8, 2024, the patient returned for a follow-up visit, reporting a significant reduction in cough after taking the previous prescription. The tongue was dark red with reduced teeth marks, the sublingual veins were slightly less tortuous, the tongue coating was white and slightly greasy, and the pulse remained thready. Overall, the condition had improved, but consolidation treatment was still necessary. The prescription consisted of a combination of traditional Chinese medicine herbs with the addition of 20g of Coix seed to enhance the spleen-strengthening and dampness-removing effects, further improving the spleen and stomach's digestive function; and 15g of Salvia miltiorrhiza was added to strengthen blood circulation and remove blood stasis, promoting the flow of qi and blood and improving the state of blood stasis in the body.

[0076] On April 13, 2024, the patient returned for a follow-up visit. The cough had disappeared, but occasional weakness and discomfort in both lower limbs remained, worsening on rainy days and affecting sleep. Occasional dry mouth and throat were also observed. Analysis of the pathogenesis revealed that the patient's vital energy had not fully recovered, and the circulation of qi and blood was still not smooth. Furthermore, spleen deficiency impaired the transformation and transportation of fluids, obstructing the meridians and affecting the nourishment of the lower limbs. Dampness trapped in the spleen prevented the upward flow of body fluids, resulting in dry mouth. The prescription was adjusted to a combination of herbs with the addition of 12g of prepared Polygala tenuifolia, 30g of Chaenomeles speciosa, 6g of Pheretima aspergillum, 10g of Cinnamomum cassia, 10g of Terminalia chebula, and 30g of raw dragon bone (decocted first). The patient was advised that since they had been taking the medication for 6 months, they could discontinue it and have a follow-up gastroscopy at a later date.

[0077] A follow-up visit on May 23, 2024, revealed no symptoms such as epigastric distension, pain, dry mouth, or bitter taste. A repeat gastroscopy performed at this hospital on May 11, 2024, showed chronic gastritis. Pathological examination revealed: (gastric angle) mild chronic inflammation of the superficial gastric mucosa with mild intestinal metaplasia; (gastric antrum) mild chronic inflammation of the superficial gastric mucosa with mild intestinal metaplasia (e.g., Figure 2 ).

[0078] After treatment with the traditional Chinese medicine composition, the patient with atrophic gastritis accompanied by moderate intestinal metaplasia and mild dysplasia experienced symptom relief, and the gastric mucosal intestinal metaplasia and mild dysplasia disappeared. This indicates that the traditional Chinese medicine composition can effectively reverse the intestinal metaplasia and dysplasia lesions in atrophic gastritis, making it a reliable drug for the treatment of such diseases and possessing potential for further development.

[0079] The present invention has been described in detail above. Those skilled in the art will recognize that the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope. While specific embodiments have been provided, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including modifications made using conventional techniques known in the art that depart from the scope disclosed herein.

Claims

1. A traditional Chinese medicine composition, characterized in that, Made from raw materials comprising the following parts by weight: Astragalus membranaceus 10-15 parts, Atractylodes macrocephala 8-10 parts, Poria cocos 10-15 parts, Citrus reticulata 8-10 parts, Pinellia ternata 5-8 parts, Cyperus rotundus 12-15 parts, Panax notoginseng 3-5 parts, Curcuma longa 10-12 parts, Actinidia chinensis root 15-20 parts, Scutellaria barbata 15-20 parts, Hedyotis diffusa 10-15 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is any one of the following: A1) The traditional Chinese medicine composition also includes 6-10 parts of vinegar-processed Bupleurum chinense, 8-12 parts of Scutellaria baicalensis, and 12-18 parts of Curcuma zedoaria; A2) The traditional Chinese medicine composition also includes 15-30 parts of calcined oyster shell and 10-20 parts of prunella vulgaris; A3) The traditional Chinese medicine composition further includes 6-10 parts of Platycodon grandiflorus and 6-10 parts of Saposhnikovia divaricata; A4) The traditional Chinese medicine composition further includes 15-25 parts of coix seed and 10-15 parts of salvia miltiorrhiza; The traditional Chinese medicine composition described in A5) further includes 10-15 parts of prepared Polygala tenuifolia, 20-40 parts of Chaenomeles speciosa, 5-8 parts of Pheretima aspergillum, 8-12 parts of Cinnamomum cassia, 8-12 parts of Terminalia chebula and 20-40 parts of raw dragon bone.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from raw materials comprising the following parts by weight: Astragalus membranaceus 15 parts, Atractylodes macrocephala 10 parts, Poria cocos 10 parts, Citrus reticulata 10 parts, Pinellia ternata 5 parts, Cyperus rotundus 15 parts, Panax notoginseng 3 parts, Curcuma longa 12 parts, Actinidia chinensis root 15 parts, Scutellaria barbata 15 parts, Hedyotis diffusa 15 parts.

4. The traditional Chinese medicine composition according to claim 3, characterized in that, The traditional Chinese medicine composition is any one or a combination of the following: B1) The traditional Chinese medicine composition also includes 8 parts of vinegar-processed Bupleurum chinense, 10 parts of Scutellaria baicalensis tablets, and 15 parts of Curcuma zedoaria; B2) The traditional Chinese medicine composition also includes 20 parts of calcined oyster shell and 15 parts of prunella vulgaris; B3) The traditional Chinese medicine composition also includes 8 parts Platycodon grandiflorus and 8 parts Saposhnikovia divaricata; B4) The traditional Chinese medicine composition also includes 20 parts of coix seed and 15 parts of salvia miltiorrhiza; B5) The traditional Chinese medicine composition also includes 12 parts of prepared Polygala tenuifolia, 30 parts of Chaenomeles speciosa, 6 parts of Pheretima aspergillum, 10 parts of Cinnamomum cassia, 10 parts of Terminalia chebula and 30 parts of raw dragon bone.

5. The traditional Chinese medicine composition according to any one of claims 1-4, characterized in that, The traditional Chinese medicine composition is a decoction.

6. The method for preparing the traditional Chinese medicine composition according to claim 5 includes the following steps: adding water to the raw materials for decoction, filtering, and obtaining the traditional Chinese medicine composition; preferably, the decoction is performed 2 to 3 times, and the decoctions are combined; the amount of water used for each decoction is 5 to 10 times the total mass of the raw materials; and the decoction time is 1 to 1.5 hours each time.

7. The use of the traditional Chinese medicine composition according to any one of claims 1-5 or the traditional Chinese medicine composition prepared by the method according to claim 6 in any of the following: C1) Prepare drugs for the prevention and / or treatment of chronic atrophic gastritis; C2) Prepare drugs for the prevention and / or treatment of precancerous lesions of the stomach; C3) Prepare drugs for the prevention and / or treatment of chronic atrophic gastritis with low-grade intraepithelial neoplasia; C4) Prepare a drug to improve gastric mucosal lesions, wherein the gastric mucosal lesions include one or more of the following: inflammation, atrophy, intestinal metaplasia, and low-grade intraepithelial neoplasia; C5) Prepare drugs for the prevention of gastric cancer.

8. The application according to claim 7, characterized in that, The chronic atrophic gastritis mentioned refers to chronic atrophic gastritis that is negative for Helicobacter pylori.

9. The application according to claim 7 or 8, characterized in that, The drug is used to prevent or treat diseases diagnosed in Traditional Chinese Medicine as spleen and stomach deficiency with phlegm and blood stasis; or, The drug is used to prevent or treat diseases diagnosed as spleen deficiency and blood stasis syndrome in traditional Chinese medicine.

10. A medicament having any one of the following functions, comprising the traditional Chinese medicine composition according to any one of claims 1-5 or the traditional Chinese medicine composition prepared by the method according to claim 6, and pharmaceutically acceptable excipients thereof; D1) Prevention and / or treatment of chronic atrophic gastritis; D2) Prevention and / or treatment of precancerous lesions of the stomach; D3) Prevention and / or treatment of chronic atrophic gastritis with low-grade intraepithelial neoplasia; D4) Prepare a drug to improve gastric mucosal lesions, wherein the gastric mucosal lesions include one or more of the following: inflammation, atrophy, intestinal metaplasia, and low-grade intraepithelial neoplasia; D5) Prevents stomach cancer.

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