A traditional Chinese medicine composition for treating precancerous lesions of atrophic gastritis and a preparation method thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating precancerous lesions of atrophic gastritis and a preparation method thereof. Raw material medicines of the traditional Chinese medicine composition are as follows: Astragalus membranaceus, Fructus Mume, Cinnamomum cassia, Curcuma zedoary, raw chicken gizzard, Coptis chinensis and honey-fried licorice. The traditional Chinese medicine composition has remarkable curative effect, has advantages in improving gastric mucosa pathology, endoscopic score, clinical symptoms and syndrome compared with Weifuchun Capsules, a Chinese patent drug commonly used for treating precancerous lesions of atrophic gastritis, and has no obvious adverse reactions and good safety.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology. Specifically, this invention relates to a traditional Chinese medicine composition for treating atrophic gastritis and precancerous lesions, and its preparation method. Background Technology

[0002] Precancerous lesions of atrophic gastritis encompass four pathological stages: chronic atrophic gastritis (CAG), intestinal metaplasia (IM), low-grade intraepithelial neoplasia (LGD), and high-grade intraepithelial neoplasia (HGD). It is a serious disease that severely endangers public health and significantly impacts patients' quality of life. Currently, risk factors for precancerous lesions of atrophic gastritis are considered to primarily include Helicobacter pylori (Hp) infection, bile reflux, age, family history of gastric cancer, high-salt diet, and smoking. Modern medicine believes that for HGD where the extent of the lesion can be clearly defined endoscopically, aggressive endoscopic treatment or further surgical intervention is necessary, while other stages are primarily treated with medical intervention. Treatment options mainly include dietary and lifestyle adjustments, *H. pylori* eradication, folic acid supplementation, and symptomatic treatment (such as prokinetic drugs, digestive enzyme preparations, and acid-suppressing drugs). After *H. pylori* eradication therapy, gastric mucosal atrophy and intraepithelial neoplasia (IM) can be alleviated to some extent in confirmed *H. pylori*-positive patients, but IM cannot be reversed, nor does it inhibit or reverse dysplasia.

[0003] In the field of traditional Chinese medicine (TCM) treatment, although proprietary Chinese medicines for treating atrophic gastritis and precancerous lesions have gained a certain market share, the vast majority of these medicines are based on ancient prescriptions with modifications or are modern physicians' empirical formulas. Therefore, there are numerous types of proprietary Chinese medicines, and treatment often focuses on improving certain specific symptoms and syndromes. While the commercially available proprietary Chinese medicines for treating atrophic gastritis and precancerous lesions have relatively good safety profiles, their effectiveness in improving atrophic gastritis and precancerous lesions, improving endoscopic scores, and reversing atrophic gastritis, intestinal metaplasia, and dysplasia is limited, and their efficacy urgently needs further improvement. Summary of the Invention

[0004] To overcome the shortcomings of existing technologies, the purpose of this invention is to provide a traditional Chinese medicine composition for treating atrophic gastritis and precancerous lesions that is highly effective, inexpensive, and has few side effects.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] The first aspect of this invention provides a traditional Chinese medicine composition for treating atrophic gastritis and precancerous lesions.

[0007] Furthermore, the raw materials of the traditional Chinese medicine composition are: Astragalus membranaceus, Prunus mume, Cinnamomum cassia, Curcuma zedoaria, raw chicken gizzard lining, Coptis chinensis, and prepared licorice root.

[0008] Furthermore, the traditional Chinese medicine composition consists of the following raw materials in parts by weight: Astragalus membranaceus 15-45 parts, Prunus mume 6-18 parts, Cinnamomum cassia 3-9 parts, Curcuma zedoaria 9-15 parts, raw chicken gizzard lining 6-30 parts, Coptis chinensis 3-12 parts, and Glycyrrhiza uralensis (processed) 6-12 parts.

[0009] Preferably, the traditional Chinese medicine composition consists of the following raw materials in parts by weight: Astragalus membranaceus 15-30 parts, Prunus mume 6-15 parts, Cinnamomum cassia 3-9 parts, Curcuma zedoaria 9-15 parts, raw chicken gizzard lining 10-20 parts, Coptis chinensis 6-10 parts, and Glycyrrhiza uralensis (processed) 6-10 parts.

[0010] More preferably, the traditional Chinese medicine composition consists of the following raw materials in parts by weight: 20 parts Astragalus membranaceus, 10 parts Prunus mume, 6 parts Cinnamomum cassia, 12 parts Curcuma zedoaria, 15 parts raw chicken gizzard lining, 8 parts Coptis chinensis, and 8 parts processed Glycyrrhiza uralensis.

[0011] Furthermore, the types of raw materials include dried medicinal materials, fresh medicinal materials, raw medicinal materials, processed medicinal materials, whole plant of medicinal materials, effective parts of whole plant of medicinal materials, or combinations thereof.

[0012] The rationale for the active pharmaceutical ingredient used in this invention is as follows:

[0013] Astragalus is the principal herb in this formula, tonifying the middle energizer, replenishing qi, and promoting tissue regeneration. Ume (dried plum), cinnamon, and prepared licorice are the assistant herbs. Ume is sour and astringent, and promotes the production of body fluids; the *Shennong Bencao Jing* records that ume is effective in "lowering qi...dead tissue, removing bluish-black moles, and malignant diseases." Cinnamon tonifies primordial yang, warms the spleen and stomach, and unblocks blood vessels. Prepared licorice harmonizes the middle energizer and relieves spasms; the *Shennong Bencao Jing* states that it "treats cold and heat evil qi in the five viscera and six bowels, strengthens tendons and bones, and promotes muscle growth." The balance of qi and yin is reflected in the use of astragalus, ume, and licorice together for "sour and sweet transforming yin," and cinnamon and licorice together for "pungent and sweet transforming yang," following the principle in the *Shanghan Lun*: "When yin and yang are in harmony, qi can circulate." Curcuma zedoaria and raw chicken gizzard digest stagnation, while Coptis chinensis clears heat, drains fire, detoxifies, and dries dampness; all are used as adjuvant herbs. Prepared licorice is also used as the guiding herb to harmonize the other herbs.

[0014] In this invention, "raw material" is synonymous with "active pharmaceutical ingredient," referring to the traditional Chinese medicinal materials that enable the invention to exert its active function. These materials include various forms, specifically dried, fresh, raw, processed, or prepared medicinal materials, the whole plant of the medicinal material, the effective parts of the whole plant of the medicinal material, or combinations thereof, but are not limited thereto. In some embodiments, the raw material further comprises the main active ingredients extracted from the raw material, all of which are components proven in the prior art.

[0015] In some embodiments, the traditional Chinese medicine composition further includes the active ingredients of Astragalus membranaceus, Prunus mume, Cinnamomum cassia, Curcuma zedoaria, raw chicken gizzard lining, Coptis chinensis, and processed licorice root, or medicinal salts of the active ingredients.

[0016] In some embodiments, the pharmaceutically acceptable salt includes acid addition salts and alkali addition salts.

[0017] The term "medicinal salt" as used herein includes ammonium phosphates, metal salts, salts formed with amino acids, salts formed with amines, and salts formed with other bases such as piperidine or morpholine. The term "medicinal salt" includes monosalts or disalts. Specific embodiments include ammonium, sodium, calcium, magnesium, cesium, lithium, potassium, barium, zinc, aluminum, lysine, arginine, histidine, methylamine, ethylamine, tert-butylamine, cyclohexylamine, and N. Methylglucosamine, ethylenediamine, glycine, procaine, benzathine, diethanolamine, triethanolamine, piperidine, and morpholine.

[0018] In some embodiments, the term "medicinal salt" may also include hydrates of the pharmaceutical salts containing the active ingredient of the present invention. Examples of salts include, but are not limited to, sulfates, citrates, acetates, oxalates, chlorides, hydrochlorides, bromides, hydrobromides, iodides, nitrates, hydrogen sulfates, phosphates, acid phosphates, isonicotinate, lactate, salicylates, acid citrates, tartrates, oleates, tannates, pantothenates, hydrogen tartrates, ascorbic acid salts, gentisinates, gluconates, glucuronides, glycosides, formates, benzoates, glutamates, methanesulfonates, ethanesulfonates, benzenesulfonates, p-toluenesulfonates, camphorsulfonates, naphthalenesulfonates, propionates, succinates, fumarates, maleates, malonates, mandelates, malates, palmitates, aspartate salts, phthalates, and pyrates.

[0019] In this invention, part by weight refers to any unit of weight, such as gram (g), kilogram (kg), etc.

[0020] In the above composition, the weight of the medicine is calculated based on the raw medicinal materials, and the proportions are based on weight parts. During production, the proportions can be increased or decreased proportionally. For example, large-scale production can be measured in kilograms or tons, while small-scale production can be measured in grams or milligrams. The weight can be increased or decreased, but the weight ratio of the raw medicinal materials among the components remains unchanged. The above weight ratios are obtained through scientific screening. For special patients, such as those with severe or mild illnesses, or obese or underweight patients, the proportions of the components can be adjusted accordingly, with increases or decreases not exceeding 100%, without changing the efficacy.

[0021] Furthermore, the dosage forms of the traditional Chinese medicine composition include ointments, powders, decoctions, tinctures, films, and oils.

[0022] Preferably, the dosage form of the traditional Chinese medicine composition is a powder.

[0023] In this invention, the traditional Chinese medicine composition may also be called Qiwu Weikang Powder (QWWK).

[0024] A second aspect of the present invention provides a pharmaceutical preparation.

[0025] Furthermore, the active ingredient of the pharmaceutical preparation is the traditional Chinese medicine composition described in the first aspect of this invention.

[0026] Furthermore, the pharmaceutical formulation also includes pharmaceutically acceptable buffer solutions, carriers, and / or excipients.

[0027] Furthermore, the buffer solution includes phosphate, carbonate, acetate, citrate, glycolate, lactate, borate, tartrate, or carboxylate.

[0028] Furthermore, the buffer also includes Trizma, Bicine, Tricine, MOPS, MOPSO, MOBS, Tris, Hepes, HEPBS, MES, ACES, ADA, AMP, AMPD, AMPSO, BES, CABS, CHES, DIPSO, EPPS, ethanolamine, glycine, HEPPSO, imidazole, imidazole lactate, PIPES, SSC, SSPE, POPSO, TAPS, TABS, TAPSO, and TES.

[0029] Furthermore, the carrier includes an isotonic agent, antioxidant, suspending agent, dispersant, emulsifier, chelating agent, thickener, or solubilizer.

[0030] Furthermore, the excipients include carbohydrates, polymers, lipids, or minerals.

[0031] Furthermore, the dosage forms of the pharmaceutical preparations include granules, tablets, pills, capsules, injections, oral liquids, tinctures, suppositories, mixtures, powders, lotions, films, or drops.

[0032] Furthermore, the pharmaceutically acceptable buffers, carriers, and / or excipients are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995). These substances are used as needed to aid in the stability of the drug or to help enhance the activity of the active ingredient in the drug. The active ingredient that can be used in such a pharmaceutical composition may be in the form of its original compound itself or optionally in other pharmaceutically acceptable forms. The pharmaceutical composition thus formulated may be administered in any appropriate manner known to those skilled in the art as needed.

[0033] Furthermore, pharmaceutically acceptable buffers, carriers, and / or excipients may additionally contain liquids such as water, physiological saline, glycerol, and ethanol. Additionally, auxiliary substances such as wetting agents, emulsifiers, or pH buffers may be present in the pharmaceutical composition. These carriers enable the pharmaceutical composition to be formulated into dosage forms such as granules, tablets, pills, capsules, injections, oral liquids, tinctures, mixtures, powders, lotions, films, and drops for patient ingestion.

[0034] As a non-limiting example, the dosage form of the pharmaceutical preparation is prepared as follows:

[0035] Granules: Using the traditional Chinese medicine composition described in the first aspect of the present invention as the active ingredient, pharmaceutical excipients are added, mixed, granulated, dried, and packaged to obtain traditional Chinese medicine granules containing the traditional Chinese medicine composition described in the first aspect of the present invention.

[0036] Tablets: Using the traditional Chinese medicine composition described in the first aspect of the present invention as the active ingredient, the ingredients are dried, pharmaceutical excipients are added, mixed, granulated, dried, compressed, and coated to obtain traditional Chinese medicine tablets containing the traditional Chinese medicine composition described in the first aspect of the present invention. The tablets can be plain tablets or coated tablets, such as sugar-coated, gastric-coated, or enteric-coated tablets.

[0037] Capsules: Using the traditional Chinese medicine composition described in the first aspect of the present invention as the active ingredient, the ingredients are dried, then pharmaceutical excipients are added, mixed, granulated, dried, and encapsulated to obtain a traditional Chinese medicine capsule containing the traditional Chinese medicine composition described in the first aspect of the present invention. The capsule can be a hard capsule or a soft capsule.

[0038] Oral liquid: Using the traditional Chinese medicine composition described in the first aspect of the present invention as the active ingredient, water is added and stirred until homogeneous, then pharmaceutical excipients are added, stirred until homogeneous, filtered, filled, sterilized, and packaged to obtain a traditional Chinese medicine oral liquid containing the traditional Chinese medicine composition described in the first aspect of the present invention.

[0039] Pills: Using the traditional Chinese medicine composition described in the first aspect of the present invention as the active ingredient, after drying and pulverizing, pharmaceutical excipients are added, the mixture is placed in a sugar coating pan, a polar solvent is added while rotating the sugar coating machine, the mixture is stirred, formed into pills, dried, coated, and packaged to obtain traditional Chinese medicine pills containing the traditional Chinese medicine composition described in the first aspect of the present invention.

[0040] Droplets: Using the traditional Chinese medicine composition described in the first aspect of this invention as the active ingredient, after drying and pulverizing, pharmaceutical excipients are added, mixed evenly, heated and melted, stirred evenly, made into pills, washed, dried, and packaged to obtain traditional Chinese medicine droplets containing the traditional Chinese medicine composition described in the first aspect of this invention.

[0041] The third aspect of the present invention provides a method for preparing the traditional Chinese medicine composition described in the first aspect of the present invention.

[0042] Furthermore, the method includes: weighing the raw materials according to the above-mentioned proportions of Chinese herbal medicine raw materials, pulverizing the raw materials and sieving them to obtain the final product.

[0043] Furthermore, the raw material is pulverized and then sieved through a 300-mesh sieve.

[0044] The fourth aspect of the present invention provides a method for preparing the pharmaceutical preparation described in the second aspect of the present invention.

[0045] Furthermore, the preparation method includes the following steps: extracting or processing the raw materials of the traditional Chinese medicine composition described in the first aspect of the present invention to obtain its effective components, and then using the effective components as raw materials, adding pharmaceutically acceptable buffer solutions, carriers and / or excipients as needed, and preparing the required dosage form according to conventional pharmaceutical techniques.

[0046] The fifth aspect of this invention provides the use of the traditional Chinese medicine composition described in the first aspect of this invention in the preparation of a medicament for the prevention and / or treatment of atrophic gastritis, precancerous lesions, and / or their complications.

[0047] Furthermore, the atrophic gastritis precancerous lesions include chronic atrophic gastritis and gastric precancerous lesions.

[0048] Furthermore, the precancerous lesions of the stomach include intestinal metaplasia and dysplasia.

[0049] Furthermore, the atypical hyperplasia includes low-grade atypical hyperplasia and high-grade atypical hyperplasia.

[0050] Furthermore, the complications include peptic ulcers, anemia, anxiety, depression, and malnutrition.

[0051] The sixth aspect of the present invention provides the use of the pharmaceutical preparation described in the second aspect of the present invention in the preparation of a medicament for the prevention and / or treatment of atrophic gastritis, precancerous lesions, and / or their complications.

[0052] Furthermore, the atrophic gastritis precancerous lesions include chronic atrophic gastritis and gastric precancerous lesions.

[0053] Furthermore, the precancerous lesions of the stomach include intestinal metaplasia and dysplasia.

[0054] Furthermore, the atypical hyperplasia includes low-grade atypical hyperplasia and high-grade atypical hyperplasia.

[0055] Furthermore, the complications include peptic ulcers, anemia, anxiety, depression, and malnutrition.

[0056] Advantages and beneficial effects of the present invention:

[0057] The traditional Chinese medicine composition provided by this invention has significant therapeutic effects. Compared with Weifuchun capsules, a traditional Chinese medicine commonly used in clinical practice to treat atrophic gastritis and precancerous lesions, it has advantages in improving gastric mucosal pathology, endoscopic scores, clinical symptoms and syndromes. Moreover, no obvious adverse reactions have been observed, and it has good safety and low cost. Attached Figure Description

[0058] Figure 1 This is the technical roadmap for this research. Detailed Implementation

[0059] To make the objectives, technical solutions, and beneficial effects of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments used, where the manufacturer is not specified, are all conventional products that can be purchased commercially.

[0060] Example 1: Preparation of Traditional Chinese Medicine Composition

[0061] Experimental group medication: The experimental group medication used was the traditional Chinese medicine composition of this invention—Qiwu Weikang Powder. The prescription information is as follows: Astragalus membranaceus 20g, Prunus mume 10g, Cinnamomum cassia 6g, Curcuma zedoaria 12g, raw chicken gizzard lining 15g, Coptis chinensis 8g, and prepared licorice root 8g. The raw materials were weighed according to the prescription weight ratio, pulverized into a fine powder, passed through a 300-mesh sieve, and packaged in 6g bags. Usage: 6g twice daily. The procurement and production of the powder raw materials were entrusted to Beijing Chunfeng Pharmaceutical Co., Ltd.

[0062] Control group medication: The control group received Weifuchun capsules (Hangzhou Huqingyutang Pharmaceutical Co., Ltd.). The dosage was 4 capsules each time, 3 times a day, orally, for a course of 12 weeks. Weifuchun capsules are hard capsules containing brown to dark brown powder and fine granules. The drug ingredients are red ginseng, fragrant tea vegetable, and fried immature bitter orange peel. Each capsule contains 0.35g.

[0063] Example 2: Clinical observation trial on the efficacy of the traditional Chinese medicine composition of the present invention in treating atrophic gastritis and precancerous lesions.

[0064] The following evaluation focuses on the clinical efficacy of the traditional Chinese medicine composition of this invention in treating atrophic gastritis and precancerous lesions. The specific composition ratios used should not be construed as limiting the weight composition ratios of the drugs in this invention. In conjunction with the claims, the specification, and general knowledge in the field, those skilled in the art can make any modifications or changes based on the following embodiments without departing from the spirit and scope of this invention, and such modifications are also included within the scope of this invention.

[0065] I. Research Methods and Plan

[0066] 1. Research Design

[0067] This study was a prospective, randomized, non-inferiority controlled trial. Subjects meeting the inclusion and exclusion criteria were randomized using a computer-generated random number table to produce 1-110 random numbers, which were then ranked and binned into two groups (bin 1 and bin 2) based on their numerical values. Subjects in bin 1 were assigned to the experimental group (n=55), and those in bin 2 were assigned to the control group (n=55). The experimental group received 6g of Qiwu Weikang powder orally twice daily; the control group received 4 capsules of Weifuchun orally three times daily.

[0068] Before administering the first dose of the study drug or control drug, patients underwent physical examination, trial-related laboratory assessments, completion of gastroscopy and biopsy pathology reports, TCM syndrome scores, GSRS, FDSD, HADS scores, and TCM tongue examination. Patients then entered a 12-week treatment period, during which two follow-up visits (weeks 4 and 8) were conducted, with repeated physical examinations, TCM syndrome scores, GSRS scores, and TCM tongue examinations. At week 12, the study drug was discontinued, and follow-up was conducted with repeated physical examinations, trial-related laboratory assessments, TCM syndrome scores, GSRS, FDSD, HADS scores, and TCM tongue examinations. Follow-up continued until week 24, at which point a final face-to-face follow-up was conducted, and gastroscopy and biopsy pathology reports were completed to assess pathological lesion response rate, incidence of high-grade dysplasia and gastric cancer, and safety events. Additional laboratory samples were collected, and TCM syndrome scores, GSRS, FDSD, HADS scores, and TCM tongue examinations were performed.

[0069] 2. Research Subjects

[0070] (1) Selection criteria:

[0071] ① Age 18 to 75 years old;

[0072] ②Diagnose atrophic gastritis and gastric precancerous lesions according to the "Consensus Opinion on Chronic Gastritis in China (2022, Shanghai)" and the "Expert Consensus on the Management Strategy of Precancerous State and Precancerous Lesions of Gastric Mucosa in China (2020)";

[0073] ③ The C13 breath test confirmed the absence of symptomatic Hp infection.

[0074] (2) Exclusion criteria:

[0075] ① High-grade gastric dysplasia, gastric cancer or other malignant tumors, type A gastritis, acute erosive gastritis, upper gastrointestinal bleeding, peptic ulcer, history of gastric surgery;

[0076] ② Patients with evidence of organic gastrointestinal lesions, such as pancreatitis and cirrhosis, or patients with diseases that can lead to gastrointestinal motility disorders, including hyperthyroidism, mental illness, or neurological disorders;

[0077] ③ Patients with severe systemic diseases (significant damage to the cardiovascular, cerebrovascular, liver, kidney, blood, and hematopoietic systems, as well as those with tumors);

[0078] ④ Patients who continue to use any medications that may affect gastrointestinal function, including antacids, H2 receptor antagonists, proton pump inhibitors, gastrin receptor antagonists, or traditional Chinese medicine therapies with similar effects;

[0079] ⑤ Take nonsteroidal anti-inflammatory drugs (NSAIDs);

[0080] ⑥ Women who are trying to conceive, pregnant, or breastfeeding;

[0081] ⑦ Patients who cannot undergo endoscopic follow-up after treatment;

[0082] ⑧ Patients known to have an allergic reaction to any of the drug components used in this study;

[0083] ⑨ Patients currently participating in other clinical trials.

[0084] (3) Shedding criteria:

[0085] ① Patients who develop complications or liver and kidney damage or other unforeseen emergencies that make them unsuitable to continue the trial;

[0086] ② The patient was unwilling to continue the trial during the medication process and did not complete the treatment;

[0087] ③ Cases of patients who withdrew from the trial before the course of treatment was completed, were lost to follow-up, or died for various other reasons.

[0088] A case is considered a dropout if it meets any of the criteria. If a subject drops out, the investigator should make every effort to record the reason for stopping the trial treatment and complete the Permanent Termination of Trial Visit (PTDV) on the case report form.

[0089] 3. Observation indicators and follow-up plan

[0090] (1) Observation indicators:

[0091] ① Clinical data: including basic information, clinical manifestations, signs, comorbidities, etc.;

[0092] ② Routine laboratory tests: including complete blood count, liver and kidney function tests, etc.;

[0093] ③ Biopsy pathology report: pathological histological score, pathological lesion remission rate;

[0094] ④ Endoscopic image scoring: Kimura Takemoto classification and Kyoto classification scoring were used;

[0095] ⑤ Assessment of quality of life: The TCM syndrome score, the Gastrointestinal Symptom Self-Rating Scale (GSRS), the Indigestion Symptom Diary (FDSD), and the Hospital Anxiety and Depression Scale (HADS) were used to quantify the patients' quality of life.

[0096] A. Traditional Chinese Medicine Syndrome Score: This is a peer-rating scale used by doctors to assess a patient's current syndrome type and symptom severity through symptoms. It consists of 17 questions, including primary and secondary symptoms, with each question having four levels of severity scores. The lower the score, the milder the symptom. Finally, the changes in the total symptom score and the scores of each symptom are compared.

[0097] B. Gastrointestinal Symptom Self-Rating Scale (GSRS): This is a patient symptom self-rating scale containing 15 questions, used by patients to self-evaluate gastrointestinal related symptoms. It is divided into seven levels from 0 to 6, with lower scores indicating better health.

[0098] C. Dyspepsia Symptom Diary (FDSD): This is a self-rating scale for patients' symptoms. It is divided into 8 symptoms according to the Rome IV diagnostic criteria for functional dyspepsia, and includes a self-rating score that summarizes all symptoms. The lower the score, the better the health condition.

[0099] D. Hospital Anxiety and Depression Scale (HADS): This is a patient self-rating scale that includes two parts: anxiety and depression. It is used to assess a patient's anxiety and depression status. Each part has 7 questions, divided into four levels from 0 to 3. The scoring rules vary depending on the questions, with a tendency for higher anxiety / depression scores.

[0100] ⑥ Traditional Chinese Medicine Tongue Diagnosis Instrument Report: Using the Daosheng Tongue Surface Imaging Instrument (DS01-B Tongue Surface Diagnosis and Information Acquisition System), the patient's tongue appearance is completely based on the objective evaluation results of the tongue diagnosis instrument, including 12 items such as tongue color and local characteristics (red edges and tips, ecchymosis and petechiae), coating color, coating texture (thickness, greasiness, decay, peeling), and tongue shape (thickness, teeth marks, prickles, cracks).

[0101] (2) Follow-up plan

[0102] After completing enrollment screening, collecting baseline data, and administering the first dose of medication or control medication, patients entered a 12-week treatment period. During this period, two follow-up visits were conducted (weeks 4 and 8), during which physical examinations, TCM syndrome scores, GSRS scores, and TCM tongue diagnosis were repeated. At week 12, medication was discontinued, and follow-up physical examinations were repeated, including complete blood counts, liver and kidney function assessments, TCM syndrome scores, GSRS, FDSD, HADS scores, and TCM tongue diagnosis. Follow-up continued until week 24, at which point a final face-to-face follow-up was conducted to complete gastroscopy and biopsy pathology reports to assess pathological lesion remission rates, the incidence of high-grade dysplasia and gastric cancer, and safety events. Additional laboratory samples were collected, and TCM syndrome scores, GSRS, FDSD, HADS scores, and TCM tongue diagnosis were performed.

[0103] Follow-up window periods: The window periods at weeks 4, 8, and 12 are 3 days. To prevent patients from discontinuing medication due to failure to attend follow-up appointments within the window period, 31 days' worth of medication will be administered at week 4 upon enrollment, and the remaining medication will be administered at week 8. The window period at week 24 is 7 days.

[0104] 4. Observe the endpoint

[0105] (1) Primary endpoint: pathological remission rate by week 24.

[0106] (2) Secondary endpoint:

[0107] ① The degree of decrease in endoscopic score by week 24;

[0108] ② Changes in TCM syndrome scores, GSRS, FDSD, and HADS scores at 12 and 24 weeks;

[0109] The efficacy grade index = [(TCM syndrome score before treatment - TCM syndrome score after treatment)] / TCM syndrome score before treatment * 100%. The clinical efficacy criteria are as follows:

[0110] A. Cured: Clinical symptoms and signs disappear or basically disappear, and the efficacy grade index decreases by ≥95%;

[0111] B. Marked effect: Clinical symptoms and signs are significantly improved, and the efficacy grade index decreases by >70%;

[0112] C. Effective: Clinical symptoms and signs improved, and the efficacy grade index decreased by >30%;

[0113] D. Ineffective: Clinical symptoms and signs show no significant improvement, or even worsen, with the efficacy grade index decreasing by less than 30%;

[0114] Overall effective rate = (cured + significantly effective + effective) / number of cases * 100%;

[0115] ③ Changes in tongue appearance according to Traditional Chinese Medicine at 12 and 24 weeks.

[0116] (3) Exploratory endpoints: pathological histological score at week 24; high dysplasia and incidence of gastric malignancy.

[0117] (4) Safety endpoint: Incidence of hepatic and renal insufficiency at week 12.

[0118] 5. Basis for determining sample size

[0119] Sample size estimation was performed using PASS software (v15.0), employing a non-inferiority test design. Based on previous studies, the pathological lesion remission rate after 12 weeks of treatment with Weifuchun was estimated at 55.0%, while the preliminary experiment estimated the remission rate after 12 weeks with Qiwu Weikangsan at approximately 70.0%. The Type I error α was set at 0.05, the power (1-β) at 80%, and the non-inferiority margin δ at 10%. The sample size ratio between the experimental and control groups was 1:1, resulting in a sample size of 46 patients in each group according to the sample size calculation formula. Considering a 15% dropout rate at 24 weeks, it was estimated that 55 patients needed to be included in each group, for a total of 110 patients.

[0120] 6. Statistical Analysis Methods

[0121] Normally distributed continuous variables were expressed as mean ± standard deviation (Mean ± SD), and t-tests were used for comparisons between two groups. Non-normally distributed continuous variables were expressed as medians (lower quartile, higher quartile) [M (P25, P75)], and nonparametric rank-sum tests were used for comparisons between two groups. Categorical variables were expressed as frequencies and relative frequencies (%), and χ² tests or Fisher's exact tests were used for comparisons between two groups. All primary and secondary endpoints were assessed using intention-to-treat analysis, survival analysis was performed using the Kaplan-Meier method, and log-rank tests were used for comparisons between groups. Cox proportional hazards regression models were used to assess the efficacy of different treatments and influencing factors. Two-tailed tests were used, and p < 0.05 was considered statistically significant.

[0122] The technical approach of this research is as follows: Figure 1 As shown.

[0123] II. Test Results

[0124] 1. Research Completion Status

[0125] This study enrolled 103 patients with pathologically confirmed precancerous lesions of the stomach from the Department of Gastroenterology at the China-Japan Friendship Hospital between April 2024 and August 2025. Patients were randomly assigned 1:1 using a random number table to receive either the Qiwu Weikang Powder group (QWWK, n=50) or the Weifuchun Capsule group (WFC, n=53). During the study period, 15 subjects dropped out: 10 in the Qiwu Weikang group and 5 in the Weifuchun group. Currently, 96 subjects have completed the 4-week follow-up, 94 have completed the 8-week follow-up, 92 have completed the 12-week follow-up, and 75 have completed the 24-week follow-up.

[0126] 2. Baseline Status Evaluation

[0127] 2.1 The baseline general information distribution of the two groups of subjects is shown in Table 1.

[0128] Table 1. Baseline general information distribution of the two groups of subjects

[0129]

[0130] 2.1.1 Distribution of Basic Information

[0131] As shown in Table 1, among the 103 subjects, 60 were male (58%) and 43 were female (42%). The male-to-female ratio in the observation group was 1.63:1, while in the control group it was 1.21:1. There was no significant difference in gender composition between the two groups (P < 0.05). The age distribution was comparable between the groups (p < 0.05). Among the 103 participants, the youngest was 31 years old, the oldest was 75 years old, and the mean age was (56.34 ± 10.49) years. The mean age in the Qiwu Weikang group was (57.04 ± 10.75) years, and the mean age in the Weifuchun group was (55.68 ± 10.29) years. There was no significant difference in age composition between the two groups (P < 0.05). The baseline age was 0.05, indicating that the baseline ages between the two groups were comparable. There was no significant difference in marital status between the two groups (P < 0.05). 0.05). 85.1% of the enrolled participants had a high school education or higher, with no significant difference between groups (P < 0.05). (0.05), baseline educational levels are comparable.

[0132] 2.1.2 History of Helicobacter pylori infection

[0133] All participants enrolled in the study had no history of Helicobacter pylori infection or had successfully eradicated the infection. Nine patients (18%) in the Qiwu Weikang group and eleven patients (21%) in the Weifuchun group had no history of H. pylori infection. Among those who had been infected and eradicated, the mean eradication time was 2.89 ± 3.42 years in the Qiwu Weikang group and 3.49 ± 4.32 years in the Weifuchun group. There were no statistically significant differences between the two groups in terms of H. pylori infection, eradication time, and infection status within family members (P < 0.05). 0.05).

[0134] 2.1.3 History of chronic diseases

[0135] As shown in Table 1, the distribution of past chronic disease history was similar between the two groups. There were no statistically significant differences between the groups in the incidence and onset time of diabetes, hyperlipidemia, coronary heart disease, chronic kidney disease, respiratory diseases, and thyroid-related diseases (P < 0.05). 0.05). This indicates that the two groups are comparable in terms of baseline health conditions.

[0136] 2.1.4 Personal smoking and drinking history

[0137] Regarding smoking, 15 subjects (30%) in the Qiwu Weikang group had a history of smoking, with an average annual cigarette consumption of 119.36 ± 235.68; 14 subjects (26%) in the Weifuchun group had a history of smoking, with an average annual cigarette consumption of 110.09 ± 227.57. There was no statistically significant difference between the groups in terms of smoking history or amount of smoking (P < 0.05). 0.05). In the Qiwu Weikang group, 16 subjects (32%) had a history of alcohol consumption, and in the Weifuchun group, 16 subjects (31%) had a history of alcohol consumption. There was no statistically significant difference between the groups (P < 0.05). 0.05). This indicates that the two groups have similar past smoking and drinking habits, making them comparable.

[0138] 2.1.6 Family history of related cancers

[0139] As shown in Table 1, 16 subjects (32%) in the Qiwu Weikang group had a family history of gastric cancer, of which 8 (16%) had a first-degree family history of gastric cancer; in the Weifuchun group, 23 subjects (43%) had a family history of gastric cancer, of which 9 (17%) had a first-degree family history of gastric cancer. Family history of colon cancer was relatively less common, with 6 (12%) and 2 (4%) cases respectively. There was no statistically significant difference between the two groups in terms of family history of gastric and colon cancer (P < 0.05). 0.05).

[0140] 2.2 Baseline vital signs, complete blood count, and liver and kidney function levels

[0141] As shown in Table 2, there were no statistically significant differences in vital signs such as baseline heart rate, blood pressure, height and weight between the two groups of subjects, and in blood routine indexes such as white blood cells and hemoglobin, and in liver and kidney function indexes such as ALT, AST, and creatinine between the groups (P > 0.05), and they were comparable.

[0142] Table 2 Baseline vital characteristics and blood picture distribution of two groups of subjects

[0143]

[0144] Note: WBC: total white blood cell count; HGB: hemoglobin; PLT: platelet count; ALT: alanine aminotransferase; AST: aspartate aminotransferase; eGFR: estimated glomerular filtration rate; CR: creatinine; BUN: urea; GLU: glucose.

[0145] 2.3 Baseline gastroscopy and pathological lesion conditions

[0146] 2.3.1 Gastroscopic manifestations

[0147] As shown in Table 3, the gastroscopic manifestations of the two groups of subjects were evaluated by combining the Kimura-Takemoto classification and the Kyoto classification score. According to the Kimura-Takemoto classification, the endoscopic manifestations of the two groups mainly focused on C0-C2. There were 41 cases (82%) in the Qiwu Weikang group and 43 cases (82%) in the Weifuchun group in this interval, and the overall was mainly mild to moderate atrophic gastritis, and a small number of subjects reached stage O1. From the perspective of the composition of the Kimura-Takemoto stage, there was no statistically significant difference between the two groups (P > 0.05). Specifically, referring to the Kyoto classification score for endoscopic manifestations, there were no statistically significant differences between the two groups in the four classifications of atrophy, intestinal metaplasia, fold swelling, and diffuse redness (P > 0.05); however, the score of multiple nodules in the Qiwu Weikang group was slightly higher than that in the Weifuchun group, and the total score was also slightly higher, and the difference was statistically significant (0.01 <P <0.05), but it lacked clinical practical significance. Considering comprehensively that the endoscopic manifestations of the two groups were close, they were comparable.

[0148] Table 3 Baseline gastroscopic manifestations of two groups of subjects

[0149]

[0150] 2.3.2 Distribution of pathological severity

[0151] The severity distribution of different pathological types is shown in Table 4. Among the 103 subjects included in this study, all had chronic gastric mucosal inflammation, predominantly mild to moderate (49 cases, 47.6%), moderate (48 cases, 46.6%), and severe (6 cases, 5.8%)). A small number of subjects showed active inflammation: 18 cases (17.5%) with mild active inflammation, 14 cases (13.6%) with moderate inflammation, and 1 case (1.0%) with severe active inflammation. Most subjects showed gastric mucosal atrophy, with 5 cases (4.9%) showing mild atrophy, 43 cases (41.8%) with moderate atrophy, and 4 cases (3.9%) with severe atrophy. Intestinal metaplasia was detected in 97 cases (94.1%), with mild intestinal metaplasia in 34 cases (33.0%), moderate intestinal metaplasia in 43 cases (41.8%), and severe intestinal metaplasia in 20 cases (19.4%). Nearly half of the subjects showed atypical hyperplasia, including 10 cases of focal glandular atypical hyperplasia (9.7%) and 31 cases of mild atypical hyperplasia (30.1%).

[0152] Although domestic and international guidelines have established standards for obtaining pathological samples from gastroscopy in patients with chronic gastritis, their widespread adoption in initial gastroscopy screening is still insufficient from a clinical perspective (economic factors, gastroscopy operation time, and subjects' acceptance of multiple pathological samples). In this study, most subjects only had pathological samples taken from the antrum or the antrum and suspected lesions observed endoscopically. Therefore, when assessing baseline pathological scores, the study refined the evaluation of scores for the antrum, gastric angle, and gastric body separately.

[0153] As shown in Table 5, there was no statistically significant difference in pathological scores at different sites between the two groups of subjects, and the baseline pathology was comparable.

[0154] Table 4 Baseline pathological composition of the two groups of subjects

[0155]

[0156] Table 5 Baseline pathology scores of the two groups of subjects

[0157]

[0158] 2.4 Baseline TCM syndromes, symptoms, and tongue appearance

[0159] As shown in Table 6, there were no statistically significant differences between the two groups in the scores of primary and secondary symptoms in Traditional Chinese Medicine, the FDSD rating scale, the GSRS rating scale, and the HADS anxiety and depression scale, indicating that the baseline symptoms of the two groups were comparable. Regarding tongue characteristics, as shown in Table 7, the tongue color was predominantly pale red, with a similar composition of white, yellow, and yellow-white coatings. The coating was mainly thick and greasy, and the tongue shape was swollen, with many teeth marks and cracks.

[0160] Table 6. TCM syndrome and symptom scale scores of the two groups of subjects

[0161]

[0162] Table 7 Tongue characteristics of the two groups of subjects

[0163]

[0164] 3. Results

[0165] 3.1 Improvement of primary endpoint

[0166] As shown in Table 8, the remission rate of the highest pathological score in the Qiwu Weikang group was 65.7%, and the remission rate of the average pathological score was 82.9%. The remission rates of pathological scores in the antrum, gastric angle, and gastric body were all above 60%. In the Weifuchun group, the remission rate of the highest pathological score was 55.0%, and the remission rate of the average pathological score was 60.0%. Intergroup comparisons showed that the remission rate of the Qiwu Weikang group in the antrum was not inferior to that in the Weifuchun group (P_NI>0.05), and the pathological remission rates in the gastric angle and gastric body were superior to those in the Weifuchun group (P_SUP<0.05). Specifically, the remission rates of chronic inflammation in the antrum, gastric angle, and gastric body of the Qiwu Weikang group were significantly better than those in the Weifuchun group (P_SUP<0.05), and the remission rates in atrophy, intestinal metaplasia, and dysplasia were not inferior to those in the Weifuchun group (P_NI>0.05).

[0167] Table 8. Pathological improvement rate in the two groups at 24 weeks

[0168]

[0169] Note: 1 P The NI value is the non-inferiority test value; 2 P The _SUP value is the superiority test value.

[0170] 3.2 Improvement of secondary endpoints

[0171] 3.2.1 Improved endoscopic score

[0172] As shown in Table 9, both groups showed improvement in Kyoto classification scores compared to baseline, with the improvement rate of Kyoto classification score in the Qiwu Weikang group being 62.9%. Specifically, the Qiwu Weikang group showed significantly better improvement in multiple nodules and total Kyoto classification score than the Weifuchun group (P_SUP<0.05), while the improvement in intestinal metaplasia, fold swelling, and diffuse redness was not inferior to that in the Weifuchun group (P_NI<0.05).

[0173] Table 9. Improvement rate of endoscopic scores in the two groups at 24 weeks.

[0174]

[0175] Note: 1P The NI value is the non-inferiority test value; 2 P The _SUP value is the superiority test value.

[0176] 3.2.2 Improvement in the syndrome symptom scale

[0177] As shown in Table 10, at 12 weeks, the overall effective rate of QWWK for FDSD scores was 83.3%, and the overall effective rate of Weifuchun was 66.7%, with no statistically significant difference. At 24 weeks, the overall effective rate of TCM syndrome scores of Qiwu Weikang was 87.9%, and that of Weifuchun was 71.1%, with no statistically significant difference between the two; the overall effective rate of GSRS score improvement of Qiwu Weikang was 82.4%, and that of Weifuchun was 66.7%, with no statistically significant difference between the two. Regarding HADS scores, the overall effective rate of Qiwu Weikang in improving anxiety scores was 94.7%, and that of Weifuchun was 87.0%, with no statistically significant difference between the two; the overall effective rate of Qiwu Weikang in improving depression scores was 85.2%, and that of Weifuchun was 60.7%, with Qiwu Weikang being superior to Weifuchun, and the difference was statistically significant.

[0178] Table 10 Improvement of the syndrome symptom scale in the two groups of subjects over 24 weeks

[0179]

[0180] Note: Improvement from baseline at 12 weeks on the FDSD scale.

[0181] 3.3 Safety Indicators

[0182] As shown in Table 11, there were no statistically significant differences in blood routine indicators such as white blood cell count and hemoglobin, and ALT, AST, and BUN levels between the two groups at 12 weeks (P>0.05). However, the CR was significantly decreased and eGFR was significantly increased in the Qiwu Weikang group, with statistically significant differences both within and between the groups (P<0.05). This suggests that Qiwu Weikang and Weifuchun have good safety in terms of blood routine, liver, and kidney function, and that the Qiwu Weikang formula has potential renal function protection.

[0183] Table 11 Changes in biochemical indicators in the two groups of subjects at 12 weeks

[0184]

[0185] Note: Mean difference is baseline value - 12-week follow-up value; WBC: White blood cell count; HGB: Hemoglobin; PLT: Platelet count; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; eGFR: Estimated glomerular filtration rate; CR: Creatinine; BUN: Urea; GLU: Glucose.

[0186] In summary, the traditional Chinese medicine composition provided by this invention can significantly improve the clinical symptoms of patients with atrophic gastritis and precancerous lesions. Compared with the traditional Chinese medicine Weifuchun capsules, which are commonly used in clinical practice to treat atrophic gastritis and precancerous lesions, it has advantages in improving gastric mucosal pathology, endoscopic scores, clinical symptoms and syndromes, and no obvious adverse reactions have been observed, indicating good safety.

[0187] The above description of the embodiments is only for understanding the method and core ideas of the present invention. It should be noted that those skilled in the art can make various modifications and changes to the present invention without departing from its principles, and these modifications and changes will also fall within the protection scope of the claims of the present invention.

Claims

1. A traditional Chinese medicine composition for treating atrophic gastritis and precancerous lesions, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: Astragalus membranaceus 15-45 parts, Prunus mume 6-18 parts, Cinnamomum cassia 3-9 parts, Curcuma zedoaria 9-15 parts, raw chicken gizzard 6-30 parts, Coptis chinensis 3-12 parts, and Glycyrrhiza uralensis 6-12 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: Astragalus membranaceus 15-30 parts, Prunus mume 6-15 parts, Cinnamomum cassia 3-9 parts, Curcuma zedoaria 9-15 parts, raw chicken gizzard lining 10-20 parts, Coptis chinensis 6-10 parts, and Glycyrrhiza uralensis 6-10 parts.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 20 parts Astragalus membranaceus, 10 parts Prunus mume, 6 parts Cinnamomum cassia, 12 parts Curcuma zedoaria, 15 parts raw chicken gizzard lining, 8 parts Coptis chinensis, and 8 parts prepared Glycyrrhiza uralensis.

4. The traditional Chinese medicine composition according to claim 1, characterized in that, The dosage forms of the traditional Chinese medicine composition include ointments, powders, and decoctions.

5. The traditional Chinese medicine composition according to claim 4, characterized in that, The dosage form of the traditional Chinese medicine composition is a powder.

6. A pharmaceutical preparation for treating atrophic gastritis and precancerous lesions, characterized in that, The active ingredient of the pharmaceutical preparation is the traditional Chinese medicine composition as described in any one of claims 1-5.

7. The pharmaceutical preparation according to claim 6, characterized in that, The pharmaceutical formulation also includes pharmaceutically acceptable buffer solutions, carriers, and / or excipients.

8. A method for preparing the traditional Chinese medicine composition according to any one of claims 1-5, characterized in that, The method includes: weighing the raw materials according to the above-mentioned proportions of Chinese herbal medicine raw materials, pulverizing the raw materials and sieving them to obtain the final product.

9. The method according to claim 8, characterized in that, The raw material is pulverized and then sieved through a 300-mesh sieve.

10. A method for preparing the pharmaceutical formulation according to any one of claims 6-7, characterized in that, The preparation method includes the following steps: extracting or processing the raw materials of the traditional Chinese medicine composition according to any one of claims 1-5 to obtain its effective components, and then using the effective components as raw materials, adding pharmaceutically acceptable buffer solutions, carriers and / or excipients as needed to prepare the desired dosage form.

11. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a medicament for the prevention and / or treatment of atrophic gastritis, precancerous lesions, and / or their complications.

12. Use of the pharmaceutical preparation according to any one of claims 6-7 in the preparation of a medicament for the prevention and / or treatment of atrophic gastritis, precancerous lesions, and / or complications thereof.

13. The application according to claim 11 or claim 12, characterized in that, The atrophic gastritis precancerous lesions include chronic atrophic gastritis and gastric precancerous lesions.

14. The application according to claim 13, characterized in that, The precancerous lesions of the stomach include intestinal metaplasia and dysplasia.

15. The application according to claim 14, characterized in that, The atypical hyperplasia includes low-grade atypical hyperplasia and high-grade atypical hyperplasia.

16. The application according to claim 11 or claim 12, characterized in that, The complications include anxiety and depression.

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