Pharmaceutical composition for treating chronic atrophic gastritis and precancerous lesions and application thereof

Abstract

The invention relates to a pharmaceutical composition for treating chronic atrophic gastritis and precancerous lesions and application thereof, the pharmaceutical composition is a Xiansheng stomach tonifying formula and comprises herba epimedii, codonopsis pilosula, fructus alpiniae oxyphyllae, poria cocos, roasted rhizoma atractylodis macrocephalae, caulis perllae, vinegar-processed rhizoma cyperi, galangal, rhizoma nardostachyos, vinegar-processed rhizoma sparganii, vinegar-processed curcuma zedoary, dark plum and honey-fried licorice root. The formula is scientific and reasonable, clinical research proves that the Xiansheng stomach tonifying formula has a good curative effect on clinical symptoms of patients suffering from chronic atrophic gastritis and precancerous lesions, has the effect of preventing the precancerous lesions of gastric cancer from being converted into gastric cancer, and has the effects of recovering and improving the gastric mucosa state under a gastroscope, improving the gastric mucosa quality and improving the gastric mucosa quality. The curative effect of reversing pathological changes such as atrophy, intestinal metaplasia and atypical hyperplasia and precancerous lesions is achieved; animal experiments prove that the traditional Chinese medicine composition can improve the pathological state of glandular gastric mucosa of a CAG mouse model, delay glandular gastric mucosa tissue cell senescence of the CAG mouse model and prevent gastric precancerous lesions from being converted into gastric cancer, and also has the effect of resisting gastric senescence.

Description

Technical Field

[0001] The invention relates to the field of traditional Chinese medicine, and in particular to a pharmaceutical composition for treating chronic atrophic gastritis and precancerous lesions and an application thereof. Background Art

[0002] Chronic atrophic gastritis (CAG) refers to a chronic gastric disease in which the intrinsic gastric glands atrophy and decrease in number due to long-term damaging stimulation of the gastric mucosal epithelium, which may be accompanied by intestinal gland metaplasia and (or) pseudopyloric gland metaplasia. It is a common and difficult disease of the digestive system. CAG is an important link in the development of gastric cancer. The development model of intestinal gastric cancer proposed by Correa (normal gastric mucosa → non-atrophic gastritis → CAG → intestinal metaplasia → dysplasia → intestinal gastric cancer) has been widely recognized. CAG is often accompanied by intestinal metaplasia (IM). A large number of studies have shown that the risk of CAG cancer is positively correlated with the scope and degree of gastric mucosal atrophy and intestinal metaplasia. CAG is accompanied by extensive IM involving the gastric antrum and gastric body, which is a late stage of CAG, and its risk of cancer is significantly increased.

[0003] At present, Western medicine has no effective drugs for the pathological changes of gastric mucosal atrophy, intestinal metaplasia, dysplasia, etc. in the above diseases. Generally, symptomatic treatment is adopted. However, the effect of traditional Chinese medicine on chronic atrophic gastritis with extensive intestinal metaplasia is becoming increasingly prominent. Traditional Chinese medicine has been used in clinical practice for many years to treat CAG. There are several Chinese patent medicines in China that can be used for CAG patients, such as Wenweishu, Yangweishu, Weifuchun, Moluodan, etc. The above Chinese patent medicines can relieve clinical symptoms to varying degrees and partially improve the pathological conditions of gastric mucosa. There is a huge gap between the efficacy of the currently marketed Chinese patent medicines for the treatment of CAG and the patient's expectations. The current Chinese patent medicines used for CAG are relatively old. For example, Wei Fuchun was launched in 1982 and Moluodan was launched in 1985, both of which are nearly 40 years ago. The age, gender and syndrome pattern of CAG patients today are significantly different from the clinical epidemiological characteristics of the 1980s. Clinically, there is an urgent need for dosage forms that are consistent with the current clinical epidemiological laws, TCM syndrome characteristics, and social living conditions, and that are novel and have excellent efficacy, especially for the pathological manifestations of CAG, such as atrophy, intestinal metaplasia, and intraepithelial neoplasia (dysplasia), which have good clinical efficacy, and can prevent CAG from becoming cancerous, and have unique clinical efficacy. New Chinese herbal compound drugs for the treatment of chronic atrophic gastritis Summary of the invention

[0004] 1. Technical issues to be resolved

[0005] The present invention provides a pharmaceutical composition for treating chronic atrophic gastritis and precancerous lesions and its use, the purpose of which is to solve the problem that the existing drugs used for CAG patients are different from the current clinical epidemiological laws, TCM syndrome characteristics, social living conditions, poor clinical efficacy, especially poor pathological efficacy, etc.

[0006] (II) Technical solution

[0007] The first aspect of the present invention provides a pharmaceutical composition for treating chronic atrophic gastritis and precancerous lesions, comprising: Herba Epimedii, Codonopsis pilosula, Semen Alpiniae oxyphyllae, Poria cocos, stir-fried Atractylodes macrocephala, Sophora flavescens, vinegar-cured Cyperus rotundus, Alpinia officinalis, Nardostachys grandiflora, vinegar-cured Trillium, vinegar-cured Curcuma, Prunus mume and roasted Licorice root.

[0008] The present invention adopts the treatment principle of "warming the kidney and strengthening the spleen, regulating qi, warming the middle and unblocking the collaterals, transforming yin and harmonizing the stomach", and finally determines the components of the pharmaceutical composition through the addition and subtraction experiment. The compatibility principle of each component is as follows:

[0009] The main medicines are Epimedium and Codonopsis.

[0010] Xianlingpi, pungent, sweet, warm, belongs to the liver and kidney meridians; functions and indications: tonifying kidney yang, strengthening tendons and bones, and removing rheumatism; used for kidney yang deficiency, impotence and spermatorrhea, tendon and bone weakness, rheumatic pain, numbness and cramps, and menopausal dizziness. Codonopsis, sweet, neutral, belongs to the spleen and lung meridians; functions and indications: tonifying the spleen and lungs, nourishing blood and producing body fluid; used for spleen and lung qi deficiency, loss of appetite and fatigue, cough and asthma, qi and blood deficiency, sallow complexion, palpitations and shortness of breath, thirst due to loss of body fluid, and internal heat and thirst. The two medicines are used together to warm the kidney and strengthen the spleen, warm and tonify the kidney yang, and put the spleen yang root in the kidney yang, warm and tonify the spleen qi, tonify qi and strengthen the spleen, so that the innate kidney qi is infinite and the acquired spleen qi is endless.

[0011] The assistant medicines are Alpinia oxyphylla, Poria cocos and stir-fried Atractylodes macrocepha

[0012] Alpinia oxyphylla, pungent, warm, enters the spleen and kidney meridians, warms the spleen and stops diarrhea, controls saliva, spleen cold diarrhea, cold pain in the abdomen, and excessive saliva in the mouth. Poria, sweet, light, flat, enters the heart, lung, spleen, and kidney meridians, functions and indications: diuresis and dampness, spleen and mind, used for spleen deficiency, poor appetite, loose stools and diarrhea, edema and oliguria, phlegm and fluid, palpitations, restlessness, palpitations and insomnia; stir-fried Atractylodes macrocephala, bitter, sweet, warm, enters the spleen and stomach meridians, functions and indications: spleen and qi, dry dampness and diuresis, stop sweating, and stabilize pregnancy, used for spleen deficiency, poor appetite, abdominal distension and diarrhea, phlegm and fluid, palpitations, edema, and spontaneous sweating. The three medicines are used together to assist the main medicine in warming and tonifying the kidney and spleen, strengthening the spleen and qi, and removing dampness and stopping diarrhea.

[0013] It is supplemented with Su Geng, Vinegar Cyperus rotundus, Nardostachys grandiflora, Alpinia officinarum, Vinegar Trillium and Vinegar Curcuma.

[0014] Among them, Sugeng, pungent, warm, enters the lung and spleen meridians; functions and indications: regulating qi, relieving fullness, relieving pain, and stabilizing pregnancy; used for chest and diaphragm fullness, stomach pain, belching and vomiting. Vinegar Cyperus, pungent, slightly bitter, slightly sweet, flat, enters the liver, spleen, and triple burner meridians; functions and indications: soothing the liver and relieving depression, regulating qi, relieving fullness, regulating menstruation and relieving pain. Used for liver depression and qi stagnation, chest and flank distension and pain, spleen and stomach qi stagnation, fullness and pain in the abdomen. Gansong, pungent, sweet, warm, enters the spleen and stomach meridians, functions and indications: regulating qi and relieving pain, relieving depression and invigorating the spleen; used for fullness in the abdomen, loss of appetite, and vomiting. Gaoliangjiang, pungent, hot, enters the spleen and stomach meridians, functions and indications: warming the stomach and stopping vomiting, dispersing cold and relieving pain; used for cold pain in the abdomen, vomiting due to stomach cold, belching and acid regurgitation. The combination of Sugeng, Vinegar Cyperus, Gansong, and Liangjiang can achieve the effects of regulating qi, warming the middle, and harmonizing the stomach and relieving pain.

[0015] Vinegar-striped rhizome, pungent, bitter, neutral, enters the liver and spleen meridians; functions and indications: promotes blood circulation and qi circulation, eliminates stagnation and relieves pain, used for food stagnation and pain, chest pain and heart pain, and lumps and masses. Vinegar-striped rhizome, pungent, bitter, warm, enters the liver and spleen meridians; functions and indications: promotes qi circulation and blood circulation, eliminates stagnation and relieves pain, used for food stagnation and pain, chest pain and heart pain, and lumps and masses. Vinegar-striped rhizome and vinegar-striped rhizome are used together to digest food, eliminate stagnation and relieve pain, and clear the stagnation of collaterals. It is made with vinegar, and the acid can astringe, preventing the disadvantage of dissipating qi and blood.

[0016] The guiding drugs are black plum and roasted licorice. Black plum, nature and flavor and meridians: sour, astringent, flat, enter the liver, spleen, lung, large intestine meridians; functions and indications: astringent to the lungs, astringent to the intestines, promoting the production of body fluids, and calming ascaris; used for chronic cough due to lung deficiency, chronic diarrhea and dysentery, thirst due to deficiency heat, vomiting and abdominal pain due to ascaris. Roasted licorice, nature and flavor and meridians: sweet, flat, enter the heart, lung, spleen, stomach meridians; functions and indications: tonifying the spleen and stomach, replenishing qi and restoring the pulse; used for spleen and stomach weakness, fatigue, palpitations, and intermittent pulse. Roasted licorice has the effect of harmonizing various drugs. Black plum and roasted licorice are combined, acid and sweet transform yin, promote digestion, and can tonify the yin of the spleen and stomach without the disadvantage of nourishing yin and hindering the stomach; at the same time, it can resist the heat of warming and tonic drugs and prevent the disadvantage of warming and tonic causing internal heat.

[0017] All the medicines in the prescription are used together to tonify both the acquired and acquired constitutions, and they tonify without stagnation, warm without dryness; they regulate Qi and blood, and treat blood stasis in the collaterals; it plays the role of warming the kidney and strengthening the spleen, regulating Qi, warming the middle and unblocking the collaterals, transforming Yin and harmonizing the stomach, which fits the fundamental pathogenesis of chronic atrophic gastritis with kidney and spleen Yang deficiency, Qi stagnation, cold stagnation and collateral obstruction, and stomach Yin damage.

[0018] Preferably, the components are included, by weight: 1-300 parts of Epimedium, 1-300 parts of Codonopsis, 1-250 parts of Alpinia oxyphylla, 1-250 parts of Poria, 1-250 parts of stir-fried Atractylodes, 1-200 parts of Sophora flavescens, 1-200 parts of vinegar-soaked Cyperus rotundus, 1-150 parts of Alpinia officinalis, 1-150 parts of Nardostachys grandiflora, 1-120 parts of vinegar-soaked Trillium, 1-120 parts of vinegar-soaked Curcuma, 1-240 parts of Prunus mume and 1-120 parts of roasted Licorice root. Preferably, the components are included, by weight: 5-30 parts of Epimedium, 5-30 parts of Codonopsis, 4-20 parts of Alpinia oxyphylla, 4-20 parts of Poria, 4-20 parts of stir-fried Atractylodes, 4-20 parts of Sophora flavescens, 5-25 parts of vinegar-cured Cyperus rotundus, 3-15 parts of Alpinia officinalis, 3-15 parts of Nardostachys grandiflora, 3-10 parts of vinegar-cured Trillium, 3-10 parts of vinegar-cured Curcuma, 5-20 parts of Prunus mume and 3-10 parts of roasted Licorice root.

[0019] Furthermore, the pharmaceutical composition also includes Fritillaria thunbergii and cuttlefish bone; or roasted ginger and yam; or stir-fried immature bitter orange and stir-fried radish seed; or Pueraria root and roasted Astragalus membranaceus; or stir-fried hawthorn and chicken gizzard lining; or stir-fried Shenqu and stir-fried malt; or processed Polygala tenuifolia and stir-fried Ziziphus jujuba seeds; or Ganoderma lucidum.

[0020] Furthermore, in parts by weight, the Fritillaria thunbergii is 1-200 parts, and the cuttlefish bone is 1-300 parts; the roasted ginger is 1-200 parts, and the yam is 1-300 parts; the stir-fried immature bitter orange is 1-200 parts, and the stir-fried radish seeds are 1-300 parts; the Pueraria root is 1-300 parts, and the roasted Astragalus membranaceus is 1-300 parts; the stir-fried hawthorn is 1-200 parts, and the chicken gizzard lining is 1-200 parts; the stir-fried Shenqu is 1-250 parts, and the stir-fried malt is 1-200 parts; the processed Polygala tenuifolia is 1-200 parts, and the stir-fried Ziziphus jujuba seeds are 1-300 parts; and the Ganoderma lucidum is 1-250 parts. Preferably, in parts by weight, the Fritillaria thunbergii is 5-20 parts, and the cuttlefish bone is 10-30 parts; the roasted ginger is 5-20 parts, and the yam is 10-30 parts; the stir-fried immature bitter orange is 5-20 parts, and the stir-fried radish seeds are 10-30 parts; the Pueraria root is 15-30 parts, and the roasted Astragalus membranaceus is 15-30 parts; the stir-fried hawthorn is 5-20 parts, and the chicken gizzard lining is 5-20 parts; the stir-fried Shenqu is 10-30 parts, and the stir-fried malt is 10-30 parts; the processed Polygala tenuifolia is 5-15 parts, and the stir-fried Ziziphus jujuba seeds are 15-45 parts; and the Ganoderma lucidum is 10-30 parts.

[0021] The second aspect of the present invention provides the use of the pharmaceutical composition in the preparation of drugs for treating chronic atrophic gastritis and precancerous lesions.

[0022] Furthermore, the pharmaceutical composition treats chronic atrophic gastritis and precancerous lesions by improving clinical symptoms and resisting aging.

[0023] Furthermore, the improvement of clinical symptoms includes curing and alleviating endoscopic gastric mucosal lesions, and reversing and improving atrophy, intestinal metaplasia, dysplasia and other pathologies.

[0024] Furthermore, the anti-aging is to prevent the transformation of gastric precancerous lesions into gastric cancer, and to prevent or treat chronic atrophic gastritis and precancerous lesions by inhibiting the classic anti-aging signaling pathway of CXCR2 / p38 / p53 / p21.

[0025] The third aspect of the present invention provides a pharmaceutical composition preparation for treating chronic atrophic gastritis and precancerous lesions, wherein the pharmaceutical composition preparation comprises the pharmaceutical composition and / or added pharmaceutical excipients, and / or added food additives.

[0026] Furthermore, the pharmaceutical composition preparation is a decoction, pill, powder, granule, ointment, pill, wine, syrup, extract, lozenge, lotion, gel, tea, suppository, koji, paste, cake, lotion, oil, thread, strip, roasting agent, smoke agent, tablet, granule, bag, oral liquid, capsule, soft capsule, pill, mixture, tincture, aerosol, enema, film or injection.

[0027] (III) Beneficial effects

[0028] The present invention provides a pharmaceutical composition for treating chronic atrophic gastritis and precancerous lesions and its application, and the formula is scientific and reasonable. Based on the treatment principle of "warming the kidney and strengthening the spleen, regulating qi, warming the middle and unblocking the collaterals, transforming yin and harmonizing the stomach", the main drugs are radix scutellariae and codonopsis pilosula; the auxiliary drugs are radix oxyphyllae, tuckahoe and stir-fried atractylodes; the auxiliary drugs are radix sophorae flavescentis, vinegar cyperus, rhizoma galangae, vinegar trillium and vinegar curcuma; the auxiliary drugs are ebony and roasted liquorice.

[0029] The present invention has conducted clinical trials on patients with extensive atrophy and intestinal metaplasia of the entire stomach in the gastric antrum, gastric angle, and gastric body, indicating that the pharmaceutical composition of the present invention has a definite therapeutic effect and is safe and reliable in treating CAG, can cure and significantly reduce and improve endoscopic gastric mucosal pathological changes, and can reverse and reduce atrophy, intestinal metaplasia, dysplasia (intraepithelial neoplasia) and other pathological changes and precancerous lesions in the gastric antrum, gastric angle, and gastric body of the patient. It has shown a more significant advantage in improving gastric angle lesions, has a more prominent therapeutic effect, and has the effect of preventing gastric precancerous lesions from turning into gastric cancer.

[0030] On this basis, the present invention clarifies from the animal experiment level that the pharmaceutical composition of the present invention can improve the pathological state of the gastric mucosa in the glandular area of ​​the CAG mouse model, and is effective in treating the CAG mouse model. The pharmaceutical composition of the present invention can delay the senescence of the gastric mucosal tissue cells in the glandular area of ​​the CAG mouse model and inhibit the CXCR2 / p38 / p53 / p21 signaling pathway. The pharmaceutical composition of the present invention has an anti-aging effect, and can treat chronic atrophic gastritis by preventing and treating the aging of the stomach, and prevent the transformation of gastric precancerous lesions to gastric cancer.

[0031] In summary, the present invention can effectively treat the clinical symptoms of patients with chronic atrophic gastritis and precancerous lesions, reverse and improve the endoscopic manifestations and pathological changes of the gastric mucosa, prevent the transformation of gastric precancerous lesions into gastric cancer, and treat chronic atrophic gastritis by preventing and treating gastric aging. It also has an anti-aging effect and is a safe and efficient Chinese medicine compound preparation that should be promoted. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 The SA-β-gal staining of the gastric mucosal tissue in the glandular area of ​​each group of mice; A is the blank control group; B is the H. pylori infection single factor group; C is the blank model group; D is the Xianshen Yiwei Fang low-dose group; E is the Xianshen Yiwei Fang medium-dose group; F is the Xianshen Yiwei Fang high-dose group; G is the CXCR2 inhibitor group; the scale bars in Figures AG are 100μm;

[0033] Figure 2 Protein electrophoresis of CXCR2, p38, p53, and p21 in the glandular gastric mucosal tissue of each group of mice; the BC group was the blank control group; the HP group was the H. pylori infection single factor group; the BM group was the H. pylori infection combined with MNNG mutagenesis dual factor group, or called the blank model group; the GL group was the Xianshen Yiwei Fang low-dose group; the GM group was the Xianshen Yiwei Fang medium-dose group; the GH group was the Xianshen Yiwei Fang high-dose group; and the CI group was the CXCR2 inhibitor group. DETAILED DESCRIPTION

[0034] To further illustrate the technical means and effects of the present invention, the present invention is further described below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention, rather than to limit the present invention.

[0035] Example 1

[0036] Xianshen Yiwei Fang: Xianlingpi 12g, Codonopsis pilosula 12g, Alpinia oxyphylla 10g, Poria 10g, stir-fried Atractylodes macrocephala 10g, Sophora japonica 10g, vinegar Cyperus rotundus 15g, Alpinia officinalis 6g, Nardostachys grandiflora 5g, vinegar Trillium 6g, vinegar Curcuma 6g, Plum 12g and Radix Glycyrrhizae Preparata 6g. This embodiment is decocted according to the traditional Chinese medicine decoction. First, soak all the medicines in clear water for 60 minutes, boil the first decoction over high heat and cook for 5 minutes, then decoct over low heat for 30 minutes, pour out the juice and decoct the second decoction according to the above method, mix the two decoctions, take them twice, take 250ml once, take twice a day, and take them 60 minutes after breakfast and dinner. In practical applications, the preparation methods are not limited to the above methods. According to actual needs, the preparation methods can be prepared into pills, powders, granules, ointments, pills, wines, syrups, extracts, lozenges, dews, gels, teas, suppositories, kojis, pastes, cakes, lotions, oils, threads, strips, roasting agents, smoke agents, tablets, granules, bags, oral liquids, capsules, soft capsules, pills, mixtures, tinctures, aerosols, enemas, films or injections, etc.

[0037] Example 2

[0038] Xianshen Yiwei Recipe: Xianlingpi 24g, Codonopsis pilosula 24g, Alpinia oxyphylla 20g, Poria 20g, stir-fried Atractylodes macrocephala 20g, Sophora japonica 20g, vinegar-cured Cyperus rotundus 30g, Alpinia officinalis 12g, Nardostachys grandiflora 10g, vinegar-cured Trillium 12g, vinegar-cured Curcuma 12g, Plum ebony 24g and roasted Licorice root 12g. The preparation method is the same as that of Example 1.

[0039] Example 3

[0040] Xianshen Yiwei Recipe: Xianlingpi 6g, Codonopsis pilosula 6g, Alpinia oxyphylla 5g, Poria 5g, stir-fried Atractylodes macrocephala 5g, Sophora japonica 5g, vinegar-cured Cyperus rotundus 8g, Alpinia officinalis 3g, Nardostachys grandiflora 3g, vinegar-cured Trillium 3g, vinegar-cured Curcuma 3g, Prunus mume 6g and roasted Licorice root 3g. The preparation method is the same as that of Example 1.

[0041] Example 4

[0042] Xianshen Yiwei Fang: the composition of Example 1 is added with 12g of Fritillaria thunbergii and 20g of cuttlefish bone; the preparation method is the same as that of Example 1. It is suitable for chronic atrophic gastritis accompanied by symptoms of heartburn and acid reflux.

[0043] Example 5

[0044] Xianshen Yiwei Fang: add 12g of roasted ginger and 15g of yam to the composition of Example 1; the preparation method is the same as that of Example 1. It is suitable for treating chronic atrophic gastritis with symptoms of loose stools and diarrhea.

[0045] Example 6

[0046] Xianshen Yiwei Recipe: Add 12g of stir-fried Citrus aurantium and 15g of stir-fried Radish Seed to the composition of Example 1; the preparation method is the same as that of Example 1. It is suitable for treating chronic atrophic gastritis with symptoms of abdominal distension and constipation.

[0047] Example 7

[0048] Xianshen Yiwei Fang: The composition of Example 1 is added with 20g of Pueraria root and 20g of roasted Astragalus; the preparation method is the same as that of Example 1. It is suitable for chronic atrophic gastritis accompanied by symptoms of dry mouth and fatigue.

[0049] Example 8

[0050] Xianshen Yiwei Fang: add wine scutellaria baicalensis 12g and artemisia annua 15g to the composition of Example 1; the preparation method is the same as that of Example 1. It is suitable for chronic atrophic gastritis with symptoms of bitter taste in the mouth in the morning.

[0051] Example 9

[0052] Xianshen Yiwei Fang: The composition of Example 1 is added with 12g of fried hawthorn and 12g of chicken gizzard lining; the preparation method is the same as that of Example 1. It is suitable for chronic atrophic gastritis caused by indigestion of gastric distension after eating meat.

[0053] Example 10

[0054] Xianshen Yiwei Fang: The composition of Example 1 is added with 15g of stir-fried Shenqu and 15g of stir-fried malt; the preparation method is the same as that of Example 1. It is suitable for chronic atrophic gastritis accompanied by symptoms of poor appetite and weight loss.

[0055] Embodiment 11

[0056] Xianshen Yiwei Recipe: Add 10g of processed Polygala tenuifolia and 30g of stir-fried Ziziphus jujuba seeds to the composition of Example 1; add 20g of Ganoderma lucidum for early awakening in the middle of the night; the preparation method is the same as that of Example 1. It is suitable for the symptoms of chronic atrophic gastritis accompanied by insomnia.

[0057] The TCM pathogenesis of CAG is "kidney yang deficiency, spleen deficiency, qi stagnation, cold stagnation, and spleen and stomach yin deficiency", and the incidence of CAG increases with age. The current prevalence of CAG is gradually increasing, and it is showing a trend of younger age. Guben Tongluo Fang is a pharmaceutical composition for the early treatment of chronic atrophic gastritis by the applicant, and has achieved very good therapeutic effects. This application is further innovative on the basis of Guben Tongluo Fang, based on the correlation between CAG and aging, and the TCM concept of "wei tiannian", but according to the inventor's in-depth understanding of the TCM pathogenesis, TCM treatment principles, functional composition, and anti-aging mechanism of the disease, the pharmaceutical composition of the present invention, Xianshen Yiwei Fang, is proposed. The present invention uses all the medicines in the whole prescription together, and supplements both the acquired and acquired, and supplements without stagnation, warms without dryness; regulates qi and blood, and treats blood stasis at the same time, and obtains the treatment principle of "warming the kidney and spleen, regulating qi, warming the middle and unblocking the collaterals, and transforming yin and harmonizing the stomach".

[0058] The beneficial effects of the present invention are demonstrated as follows:

[0059] Part I: Clinical Trials

[0060] 1. Research Methods

[0061] The patients included in this study were all diagnosed with chronic atrophic gastritis with extensive intestinal metaplasia in the outpatient clinic of the Department of Spleen and Stomach of Guang'anmen Hospital, China Academy of Chinese Medical Sciences and the Endoscopy Center. The TCM syndrome type standards of the 2009 Consensus on the Diagnosis and Treatment of Chronic Atrophic Gastritis, the endoscopic standards of the 2004 Trial Opinions on Endoscopic Classification and Treatment of Chronic Gastritis, and the endoscopic and pathological diagnosis and treatment standards of the Consensus on Chronic Gastritis in China (2012, Shanghai) were used as reference.

[0062] Inclusion criteria: ① meet the diagnostic criteria of chronic atrophic gastritis with extensive intestinal metaplasia; ② TCM syndrome type belongs to spleen and stomach deficiency syndrome; ③ gastroscopy and pathology reports should be within 1 month before inclusion in the study; ④ age 18 to 80 years old; ⑤ no other treatment related to this disease within 1 week.

[0063] Exclusion criteria: ① Patients with autoimmune gastritis; ② Patients with combined peptic ulcer or suspected malignant transformation by pathological diagnosis; ③ Patients with other primary diseases of the heart, brain, liver, kidney and hematopoietic system, or serious diseases that affect their survival, such as malignant tumors, AIDS, etc.; ④ Patients with mental illness, patients without autonomy and without full civil capacity; ⑤ Patients with a history of gastric surgery; ⑥ Women who are pregnant or preparing for pregnancy or breastfeeding; ⑦ Patients participating in other clinical trials.

[0064] This study set up two cohort groups. Patients who met the diagnosis and inclusion criteria were divided into different groups according to the random numbers generated by statistical software.

[0065] 1. Treatment Methods

[0066] The two groups were given different Chinese medicines orally. Patients treated with Xianshen Yiwei Fang were included in the Xianshen Yiwei Fang group, referred to as Group A; patients treated with Guben Tongluo Fang were included in the Guben Tongluo Fang group, referred to as Group B.

[0067] The Chinese medicine of Group A (Xian Shen Yi Wei Fang Group) comprises: the same as that of Example 1.

[0068] The Chinese medicine in Group B (Guben Tongluo prescription group) includes: Codonopsis pilosula 15g, Poria 20g, stir-fried Atractylodes macrocephala 15g, French Pinellia 9g, Amomum villosum (added later) 6g, Epimedium 6g, Curculigo orchioides 3g, Cnidium monnieri 3g, Phellodendron chinense 15g, Anemarrhena asphodeloides 10g, Vinegar Bupleurum 10g, Vinegar Cyperus rotundus 15g, stir-fried White Peony 20g, Angelica sinensis root 20g, Vinegar Curcuma 9g, Salvia miltiorrhiza 20g, Raw Coix seeds 30g, and Liuyi powder (wrapped) 20g.

[0069] 2. Treatment

[0070] Patients were asked to return for follow-up visits and fill in the symptom scale at weeks 0, 2, 4, 6, 8, 10, and 12. 12 weeks was a course of treatment. After a course of treatment, medication was stopped, gastroscopy and pathology were reviewed, and data were collected for analysis and evaluation.

[0071] 3. Observation indicators

[0072] 3.1 TCM Syndrome Score

[0073] The symptom classification and quantitative standards were formulated with reference to the 2009 Consensus on TCM Diagnosis and Treatment of Chronic Atrophic Gastritis and the July 2009 edition of the Guiding Principles for Clinical Research on New Chinese Medicines for the Treatment of Atrophic Gastritis. The main symptoms include fullness and dull pain in the stomach, and preference for pressing and warmth, which are assigned 0, 3, 6, and 9 points according to the degree of absence, mild, moderate, and severe; the secondary symptoms include loose stools, abdominal distension after eating, fatigue, acid reflux, reduced appetite, noisy stomach, shortness of breath and laziness to speak, and vomiting of clear water, which are assigned 0, 1, 2, and 3 points according to the degree of absence, mild, moderate, and severe.

[0074] 3.2 Gastroscopy pathology score

[0075] Refer to the endoscopic and pathological diagnosis and treatment standards of the Consensus on Chronic Gastritis in China (Shanghai, 2012). According to the presence and severity of atrophy, intestinal metaplasia and dysplasia, they were scored as 0, 3, 6 and 9 points respectively.

[0076] 3.3OLGA and OLGIM staging

[0077] Refer to the gastritis staging criteria (LGA) proposed by the International Atrophy Study Group in 2005 and the intestinal metaplasia staging criteria (OLGIM) proposed by Capelle LG et al. in 2010, see Table 1.

[0078] Table 1 OLGA / OLGIM grading and staging system

[0079]

[0080] 4. Efficacy evaluation

[0081] 4.1 TCM syndrome efficacy evaluation

[0082] ①Clinical cure: symptoms and signs disappear or basically disappear, efficacy index ≥ 95%; ②Clinical marked effect: main symptoms and signs are significantly improved, 70% ≤ efficacy index < 95%; ③Clinical effectiveness: main symptoms and signs are improved, 30% ≤ efficacy index < 70%; ④Clinical ineffectiveness: main symptoms and signs are not significantly improved, or even aggravated, efficacy index < 30%. The calculation formula adopts the nimodipine method, efficacy index (%) = [(pre-treatment score - post-treatment score) / pre-treatment score × 100%].

[0083] 4.2 Pathological efficacy evaluation

[0084] ① Cured: glandular atrophy, IM, and dysplasia return to normal or disappear; ② Significantly effective: glandular atrophy, IM, and dysplasia are alleviated by 2 levels; ③ Effective: glandular atrophy, IM, and dysplasia are alleviated by 1 level; ④ Ineffective: glandular atrophy, IM, and dysplasia are not improved, or may even worsen.

[0085] 4.3 Risk Assessment of OLGA and OLGIM Grading and Staging Systems

[0086] ① Clinical cure: OLGA / OLGIM stage 0; ② Clinical marked effect: OLGA / OLGIM stage decreased by at least 2 stages; ③ Clinical effectiveness: OLGA / OLGIM stage decreased by 1 stage; ④ Clinical ineffectiveness: OLGA / OLGIM stage did not decrease, or even increased. The scores of each part (gastric antrum, gastric angle, gastric body) before treatment and the scores of each part (gastric antrum, gastric angle, gastric body) after treatment were statistically analyzed, and the significant difference was considered effective.

[0087] 5. Statistical methods

[0088] All completed questionnaires, symptom scales, and risk assessment forms were sorted out and statistically analyzed using SPSS26.0 software. F test and t test were used for measurement data that conformed to normal distribution, non-parametric test was used for measurement data that were not normally distributed, chi-square test was used for count data, and rank sum test was used for rank data. P<0.05 was considered statistically significant.

[0089] 2. Results Analysis

[0090] 1. Patient inclusion

[0091] A total of 126 patients were included in this study, including 78 patients in group A. The patient dropout rate during the clinical trial was 4.76%, which met the requirement of less than 20%. Finally, a total of 120 patients were included in this study, including 75 patients in group A and 45 patients in group B.

[0092] 2. Baseline characteristics

[0093] 2.1 Demographic baseline characteristics

[0094] The demographic baseline characteristics of the two groups of patients were compared. The age and BMI of the two groups of patients met the normality test and variance homogeneity test, and the two independent sample t test was used; the chi-square test was used for gender. After testing, there was no significant difference in the distribution of age, gender and BMI between the two groups of patients. The specific results are shown in Table 2.

[0095] Table 2 Demographic baseline information of the two groups of patients

[0096]

[0097] 2.2 Baseline characteristics of the disease

[0098] The baseline characteristics of the two groups of patients were compared. The TCM syndrome scores of the two groups of patients were in accordance with the normality test and variance homogeneity test, and the two independent sample t test was used; the gastric antral atrophy score, gastric angle atrophy score, gastric body atrophy score, gastric antral intestinal metaplasia score, gastric angle intestinal metaplasia score, gastric body intestinal metaplasia score, OLGA score, and OLGIM score of the two groups of patients did not conform to the normal distribution, and the Mann-Whitney U test was used for each test. After the test, there was no significant difference in the scores of the two groups of patients before treatment. The specific results are shown in Table 3.

[0099] Table 3 Baseline characteristics of the two groups of patients

[0100]

[0101] 3. Outcome indicators and conclusions

[0102] 3.1 Changes in TCM syndrome scores before and after treatment

[0103] After taking Chinese medicine for 2, 4, 6, 8, 10, and 12 weeks, the average TCM syndrome scores of the two groups of patients showed a downward trend overall, and there was a significant difference between the 12th week of treatment and the pre-treatment (P<0.001). Among them, the TCM syndrome scores of group A patients decreased by an average of 20.36 after 12 weeks of treatment, and the average decrease of group B was 15.49, and there was a significant difference between the two groups (P=0.001). The specific results are shown in Table 4.

[0104] Table 4 Changes in TCM syndrome score treatment ( n=120)

[0105]

[0106] Note: Compared with before treatment, #P<0.001

[0107] After 12 weeks of treatment, the overall effective rate of group A was 94.67%, of which 20 patients were cured, accounting for 26.67%; 22 patients were significantly effective, accounting for 29.33%; 29 patients were effective, accounting for 38.67%; and 4 patients were ineffective, accounting for 5.33%. The overall effective rate of group B was 91.10%, of which 1 patient was cured, accounting for 2.20%; 11 patients were significantly effective, accounting for 24.40%; 29 patients were effective, accounting for 64.50%; and 4 patients were ineffective, accounting for 8.90%. According to the chi-square test, there was no significant difference in the total effective rate between the two groups. The specific results are shown in Table 5.

[0108] Table 5 Evaluation of the efficacy of TCM syndromes in 12-week treatment

[0109]

[0110] In summary, the TCM syndrome scores of the two groups of patients were similar and comparable before treatment. The average TCM syndrome score of group A patients before treatment was 28.80. After 2 weeks of treatment, the average syndrome score of patients decreased significantly, about 33.02%, and 47.95% after 4 weeks of treatment. Then, with the extension of treatment time, the syndrome score of patients gradually decreased. After 12 weeks of treatment, the average syndrome score of patients decreased by 70.69% compared with that before treatment. The syndrome score of each stage was statistically significant compared with that before treatment (P<0.001); the average TCM syndrome score of group B patients before treatment was 28.47. After 2 weeks of treatment, the average syndrome score decreased by 16.09%, 35.62% after 4 weeks of treatment, and 54.41% after the end of the treatment. In general, the decline in TCM syndrome score of group A patients after treatment was significantly greater than that of group B. From the beginning of treatment to the end of the 12 weeks of treatment, the decline in the score of group A was always higher than that of group B. This shows that compared with Chinese medicine B, the treatment effect of Chinese medicine A is more significant and lasting. Treatment with Chinese medicine A can effectively improve the patient's symptom score, relieve the patient's clinical symptoms, and significantly improve the patient's quality of life.

[0111] 3.2 Pathological changes of gastric mucosa before and after treatment

[0112] 3.2.1 Changes in gastric antral pathological scores before and after treatment and evaluation of therapeutic efficacy

[0113] After 12 weeks of treatment, the scores of gastric antral atrophy and intestinal metaplasia in both groups were lower than those before treatment, which was statistically significant after rank sum test (P<0.001). The comparison between groups A and B showed that the average gastric antral atrophy score of group A decreased by 3.68, and the average score of group B decreased by 3.07; the average score of gastric antral intestinal metaplasia of group A decreased by 1.88, and the average score of group B decreased by 1.86. There was no significant difference between the two groups after test. The specific results are shown in Tables 6 and 7.

[0114] Table 6 Changes in the pathological score of gastric antral atrophy during treatment ( n=120)

[0115]

[0116] Note: Compared with before treatment, #P<0.001

[0117] Table 7 Changes in pathological scores of gastric antral intestinal metaplasia during treatment ( n=120)

[0118]

[0119] Note: Compared with before treatment, #P<0.001

[0120] After one course of treatment, the cure rate of gastric antral atrophy in group A was 56.0%, the marked efficacy rate was 8.00%, the effective rate was 17.33%, the ineffective rate was 18.67%, and the total effective rate was 81.33%; the cure rate of gastric antral intestinal metaplasia was 13.33%, the marked efficacy rate was 6.67%, the effective rate was 33.33%, the ineffective rate was 46.67%, and the total effective rate was 53.33%. After treatment, the cure rate of gastric antral atrophy in group B was 57.80%, the marked efficacy rate was 2.20%, the effective rate was 15.60%, the ineffective rate was 24.40%, and the total effective rate was 75.60%; the cure rate of gastric antral intestinal metaplasia was 17.90%, the marked efficacy rate was 4.40%, the effective rate was 33.30%, the ineffective rate was 44.40%, and the total effective rate was 55.60%. According to the chi-square test, there was no significant difference in the effective rate of the two groups of patients. The specific results are shown in Table 8.

[0121] Table 8 Evaluation of therapeutic effect of gastric antral atrophy and intestinal metaplasia

[0122]

[0123]

[0124] 3.2.2 Changes in gastric angle pathological scores before and after treatment and evaluation of therapeutic efficacy

[0125] After 12 weeks of treatment, the average scores of gastric angle atrophy and intestinal metaplasia in both groups were lower than those before treatment, which was statistically significant after rank sum test (P<0.01). The comparison between groups A and B showed that the average score of gastric angle atrophy in group A decreased by 3.88, and that in group B decreased by 1.53. The Mann-Whitney U test showed that the decrease in group A was significantly greater than that in group B (P=0.002); the average score of gastric angle intestinal metaplasia in group A decreased by 4.52, and that in group B decreased by 1.40. The Mann-Whitney U test showed that the decrease in group A was significantly greater than that in group B (P<0.001). The specific results are shown in Tables 9 and 10.

[0126] Table 9 Changes in pathological score of gastric angle atrophy during treatment ( n=120)

[0127]

[0128] Note: Compared with before treatment, *P<0.001, #P=0.001

[0129] Table 10 Changes in pathological scores of gastric horn metaplasia during treatment ( n=120)

[0130]

[0131] Note: Compared with before treatment, #P<0.001, *P<0.01

[0132] After one course of treatment, the cure rate of gastric angle atrophy in group A was 58.67%, the marked efficacy rate was 5.33%, the effective rate was 24.00%, the ineffective rate was 12.00%, and the total effective rate was 88.00%; the cure rate of gastric angle intestinal metaplasia was 52.00%, the marked efficacy rate was 6.67%, the effective rate was 32.00%, the ineffective rate was 9.33%, and the total effective rate was 90.67%. After treatment, the cure rate of gastric angle atrophy in group B was 42.20%, the marked efficacy rate was 0%, the effective rate was 13.40%, the ineffective rate was 44.40%, and the total effective rate was 55.60%; the cure rate of gastric angle intestinal metaplasia was 13.30%, the marked efficacy rate was 0%, the effective rate was 33.40%, the ineffective rate was 53.30%, and the total effective rate was 46.70%. According to the chi-square test, the effective rate of gastric angle atrophy and intestinal metaplasia in group A was significantly higher than that in group B (P<0.001). The specific results are shown in Table 11.

[0133] Table 11 Evaluation of therapeutic effect of gastric angle atrophy and intestinal metaplasia

[0134]

[0135] 3.2.3 Changes in gastric body pathological scores before and after treatment and evaluation of therapeutic efficacy

[0136] After 12 weeks of treatment, the average scores of gastric body atrophy and intestinal metaplasia in both groups were lower than those before treatment, which was statistically significant after rank sum test (P<0.001). The comparison between groups A and B showed that the average score of gastric body atrophy in group A decreased by 3.92, and that in group B decreased by 4.00. After the test, there was no significant difference between the two groups; the average score of gastric body intestinal metaplasia in group A decreased by 4.64, and that in group B decreased by 2.80. After Mann-Whitney U test, the decrease in group A was significantly greater than that in group B (P=0.001). The specific results are shown in Tables 12 and 13.

[0137] Table 12 Changes in gastric body atrophy pathological score during treatment ( n=120)

[0138]

[0139] Note: Compared with before treatment, #P<0.001

[0140] Table 13 Changes in gastric body intestinal metaplasia pathological score during treatment ( n=120)

[0141]

[0142] Note: Compared with before treatment, #P<0.001

[0143] After one course of treatment, the cure rate of gastric body atrophy in group A was 64.00%, the marked efficacy rate was 5.33%, the effective rate was 25.34%, the ineffective rate was 5.33%, and the total effective rate was 94.67%; the cure rate of gastric body intestinal metaplasia was 60.00%, the marked efficacy rate was 6.67%, the effective rate was 22.67%, the ineffective rate was 10.66%, and the total effective rate was 89.34%. After treatment, the cure rate of gastric body atrophy in group B was 62.20%, the marked efficacy rate was 0%, the effective rate was 17.80%, the ineffective rate was 20.00%, and the total effective rate was 80.00%; the cure rate of gastric body intestinal metaplasia was 31.10%, the marked efficacy rate was 8.90%, the effective rate was 26.70%, the ineffective rate was 33.30%, and the total effective rate was 66.70%. The chi-square test showed that the effective rate of gastric body atrophy in group A was significantly higher than that in group B (P=0.017), and the effective rate of gastric body intestinal metaplasia in group A was significantly higher than that in group B (P=0.002). The specific results are shown in Table 14.

[0144] Table 14 Evaluation of therapeutic effect of gastric atrophy and intestinal metaplasia

[0145]

[0146] In summary, the pathological scores of each part of the two groups were similar and comparable before treatment. After 12 weeks of treatment, the average gastric antral atrophy score of group A decreased by 69.70%, the gastric antral intestinal metaplasia score decreased by 32.64%, the gastric angle atrophy score decreased by 72.39%, the gastric angle intestinal metaplasia score decreased by 75.33%, the gastric body atrophy score decreased by 77.78%, and the gastric body intestinal metaplasia score decreased by 79.45%, and the pathological scores of each part were statistically significant compared with those before treatment (P<0.001); after treatment, the average gastric antral atrophy score of group B decreased by 63.04%, the gastric antral intestinal metaplasia score decreased by 33.63%, the gastric angle atrophy score decreased by 32.35%, the gastric angle intestinal metaplasia score decreased by 25.00%, the gastric body atrophy score decreased by 66.67%, and the gastric body intestinal metaplasia score decreased by 47.22%, and the pathological scores of each part were statistically significant compared with those before treatment (P≤0.001). Previous studies have shown that the lesions in the gastric angle of CAG patients are less likely to improve than those in the gastric antrum and gastric body. This may be due to the poor sensitivity of the gastric angle to drugs. Therefore, severe gastric angle lesions often remain after treatment, which seriously affects the quality of life of patients. This study found that after treatment, the pathological scores of each part of group A patients decreased significantly, and compared with group B, the decrease in the gastric angle atrophy score, gastric angle intestinal metaplasia score, and gastric body intestinal metaplasia score of group A patients after treatment was more obvious. This shows that the use of group A Chinese medicine to treat CAG has a definite effect, which can significantly reduce, improve, or even reverse the pathological conditions such as atrophy and intestinal metaplasia in the gastric antrum, gastric angle, and gastric body of patients. In addition, compared with group B Chinese medicine, group A Chinese medicine showed more significant advantages in improving gastric angle lesions, and its efficacy was more prominent, bringing better treatment effects to patients. All of the above can illustrate the unique advantages of group A Chinese medicine in the treatment of CAG.

[0147] 3.3 Changes in OLGA and OLGIM grading and staging scores before and after treatment

[0148] 3.3.1 Average scores of OLGA and OLGIM grading and staging systems

[0149] After one course of treatment, the average scores of OLGA and OLGIM grading and staging systems of both groups decreased, which was statistically significant (P<0.001). The average OLGA score of group A decreased by 1.99, and that of group B decreased by 1.88. After testing, there was no significant difference in the change of OLGA scores between the two groups; the average OLGIM score of group A decreased by 2.11, and that of group B decreased by 1.40. The decrease in OLGIM score of group A was significantly greater than that of group B (P=0.036). The specific results are shown in Tables 15 and 16.

[0150] Table 15 Changes in OLGA score during treatment ( n=120)

[0151]

[0152] Note: Compared with before treatment, #P<0.001

[0153] Table 16 Changes in OLGIM score during treatment ( n=120)

[0154]

[0155] Note: Compared with before treatment, #P<0.001

[0156] In summary, the OLGA / OLGIM scores of the two groups of patients before treatment were similar and comparable. After 12 weeks of treatment, the average OLGA score of group A patients decreased by 53.07%, and the average OLGIM score decreased by 50.72%; the average OLGA score of group B patients decreased by 48.96%, and the average OLGIM score decreased by 34.83%. The OLGA / OLGIM scores of both groups of patients decreased significantly compared with those before treatment (P<0.001). Compared with group B, the decrease in OLGIM scores of group A patients after treatment was more obvious, which fully demonstrates that the traditional Chinese medicine in group A has unique advantages in preventing the risk of early gastric cancer in CAG patients. 3.3.2 Changes in OLGA and OLGIM stage treatment

[0157] After one course of treatment, the OLGA grading and staging system of group A showed that the proportions of stage IV before and after treatment were 26.67% and 2.67%, stage III before and after treatment were 45.33% and 16.00%, stage II before and after treatment were 26.67% and 42.67%, stage I before and after treatment were 1.33% and 13.33%, and stage 0 before and after treatment were 0% and 25.33%. After 12 weeks of treatment, the proportions of stage III and IV decreased from 72.00% to 18.67%, and the proportions of stage 0, stage I, and stage II increased from 28.00% to 81.33%. After treatment, the OLGA grading and staging system of group B showed that the proportions of stage IV before and after treatment were 22.20% and 4.40%, stage III before and after treatment were 51.10% and 13.30%, stage II before and after treatment were 26.70% and 46.70%, stage I before and after treatment were 0% and 17.80%, and stage 0 before and after treatment were 0% and 17.80%. The proportions of stage III and IV decreased from 73.30% to 17.70%, and the proportions of stage 0, stage I, and stage II increased from 26.70% to 82.30%. The distribution of the OLGA grading and staging system before and after treatment in the two groups was statistically significant by rank sum test (P<0.001), as shown in Table 17.

[0158] Table 17 Changes in OLGA staging treatment

[0159]

[0160] After one course of treatment, the OLGIM grading and staging system of group A showed that the proportions of stage IV before and after treatment were 36.00% and 2.67%, stage III before and after treatment were 41.33% and 16.00%, stage II before and after treatment were 22.67% and 42.66%, stage I before and after treatment were 0% and 16.00%, and stage 0 before and after treatment were 0% and 22.67%. After 12 weeks of treatment, the proportion of stage III and stage IV decreased from 77.33% to 18.67%, and the proportion of stage 0, stage I, and stage II increased from 22.67% to 81.33%. After treatment, the proportions of stage IV in group B were 28.90% and 6.70% before and after treatment, 46.70% and 17.80% before and after treatment, 24.40% and 55.50% before and after treatment, 0% and 15.60% before and after treatment, and 0% and 4.40% before and after treatment, respectively. The proportions of stage III and IV decreased from 75.60% to 24.50%, and the proportions of stage 0, stage I, and stage II increased from 24.40% to 75.50%. The distribution of the OLGIM grading and staging system before and after treatment in the two groups was statistically significant by rank sum test (P<0.001), as shown in Table 18.

[0161] Table 18 Changes in OLGIM staging and treatment

[0162]

[0163]

[0164] In summary, after 12 weeks of treatment, the proportion of patients in group A who were in the OLGA high-risk group for gastric cancer decreased from 72.00% to 18.67%, and the proportion of patients in the OLGIM high-risk group for gastric cancer decreased from 77.33% to 18.67%; the proportion of patients in the OLGA low-risk group for gastric cancer increased from 28.00% to 81.33%, and the proportion of patients in the OLGIM low-risk group for gastric cancer increased from 22.67% to 81.33%. After treatment, the proportion of patients in group B who were in the OLGA high-risk group for gastric cancer decreased from 73.3% to 17.7%, the proportion of patients in the low-risk group increased from 26.7% to 82.3%, the proportion of patients in the OLGIM high-risk group decreased from 75.6% to 24.5%, and the proportion of patients in the low-risk group increased from 24.4% to 75.5%. Compared with before treatment, the OLGA and OLGIM high-risk groups of both groups decreased significantly (P<0.001), but there was no significant difference between the two groups.

[0165] 3.3.3 Efficacy evaluation of OLGA and OLGIM grading and staging

[0166] After 12 weeks of treatment, the cure rate of group A according to OLGA classification was 25.33%, the marked efficacy was 21.33%, the effective rate was 34.67%, the ineffective rate was 18.67%, and the total effective rate was 81.33%; the cure rate according to OLGIM classification was 22.67%, the marked efficacy was 21.33%, the effective rate was 37.33%, the ineffective rate was 18.67%, and the total effective rate was 81.33%. After treatment, the cure rate of group B according to OLGA grading and staging was 17.78%, the marked efficacy rate was 26.67%, the effective rate was 35.55%, the ineffective rate was 20.00%, and the total effective rate was 80.00%. After chi-square test, there was no significant difference in the OLGA effective rate between the two groups of patients; the cure rate of OLGIM grading and staging was 4.45%, the marked efficacy rate was 31.11%, the effective rate was 31.11%, the ineffective rate was 33.33%, and the total effective rate was 66.67%. After chi-square test, there was no significant difference in the OLGIM effective rate between the two groups of patients. The specific results are shown in Table 19.

[0167] Table 19 Evaluation of efficacy of OLGA / OLGIM grading and staging after 12 weeks of treatment

[0168]

[0169]

[0170] In summary, after 12 weeks of treatment, the total effective rate of OLGA staging in group A was 81.33%, and the total effective rate of OLGIM staging was 81.33%; the total effective rate of OLGA staging in group B was 80.00%, and the total effective rate of OLGIM staging was 66.67%. Although the total effective rates of OLGA / OLGIM in group A were higher than those in group B, there was no significant difference between the two groups.

[0171] The above results show that the use of group A Chinese medicine treatment can significantly reduce the OLGA and OLGIM scores and risk stratification of patients, and reduce the risk of gastric cancer in patients. In summary, timely use of group A Chinese medicine intervention can significantly reduce the risk of cancer in patients with chronic atrophic gastritis with extensive intestinal metaplasia, which is of great significance for preventing the occurrence of early gastric cancer and improving the public health level.

[0172] Part II: Animal Experiments

[0173] Based on the significant experimental results of the clinical trial of Chinese medicine A, the present invention further cuts in from the perspective of cell senescence among the twelve major aging markers, and clarifies that cell senescence induced by the inflammatory effect of H. pylori infection is involved in the occurrence and development of CAG. The efficacy of Xianshen Yiwei Fang in treating CAG mouse model is clarified from the animal experiment level, and the efficacy mechanism of Xianshen Yiwei Fang in treating CAG mouse model is explored based on the CXCR2 / p38 / p53 / p21 signaling pathway.

[0174] 1 Experimental Materials

[0175] 1.1 Experimental animals

[0176] There were 7 mice in the blank control group, 9 mice in the H. pylori infection single factor group, and 60 mice in the H. pylori infection combined with MNNG mutagenesis dual factor group.

[0177] 1.2 Experimental drugs

[0178] Examples 1 to 11 are all pharmaceutical compositions of the present invention, having similar pharmacological and pharmacodynamic effects. This experiment is conducted using the pharmaceutical composition of Example 1 as an example. During the experiment, the oral administration dose for mice was converted to the medium dose of Xianshen Yiwei Fang (Example 1) according to the equivalent dose conversion coefficient between adults and mice. The low dose was 0.5 times the medium dose, and the high dose was 2 times the medium dose.

[0179] 2 Experimental methods and results

[0180] 2.1 Experimental mouse grouping and intervention methods

[0181] Using the Rand function, 60 mice in the H.pylori infection combined with MNNG mutagenesis dual factor group were sorted in ascending order of weight, and every 5 mice were divided into a compatibility group according to the weight order, and then divided into 5 random groups, namely the blank model group (H.pylori infection combined with MNNG mutagenesis dual factor group), Xianshen Yiwei Fang low-dose group, Xianshen Yiwei Fang medium-dose group, Xianshen Yiwei Fang high-dose group, and CXCR2 inhibitor group, with 12 mice in each group. The mice in the Xianshen Yiwei Fang low-dose group, Xianshen Yiwei Fang medium-dose group, and Xianshen Yiwei Fang high-dose group were gavaged with low, medium, and high doses of the corresponding Chinese medicine once a day, and the gavage volume of each mouse was 20mL / kg. The mice in the CXCR2 inhibitor group were intraperitoneally injected with CXCR2 inhibitor (SB225002) (1 mg / kg / time), twice a week (Tuesday and Saturday), and the intraperitoneal injection volume was 0.1mL / 10g. The CXCR2 inhibitor was configured according to the configuration method of the Selleck official website. Mice in the blank control group, H.pylori infection single factor group, and blank model group were fed in a conventional manner. Mice in the above groups were killed after 8 weeks of intervention, and the gastric mucosal tissues of the glandular area of ​​the mice were cut, part of which was fixed in tissue fixative (10% neutral formalin solution), part of which was used for frozen sections, and part of which was stored in a -80°C refrigerator.

[0182] 2.2 Pathological grading and scoring of the gastric mucosal tissue in the glandular area of ​​mice

[0183] The fixed glandular gastric mucosal tissue was obtained, embedded in paraffin, sliced, and stained with hematoxylin-eosin (HE), and then submitted to a pathologist for grading. The pathological diagnosis grading standard referred to the "Guidelines for the Diagnosis and Treatment of Chronic Gastritis in China (2022, Shanghai)".

[0184] Atrophy: No reduction in the number of gastric glands is normal; mild is when the number of gastric glands reduced is less than 1 / 3 of the original glands; moderate is when the number of gastric glands reduced is between 1 / 3-2 / 3 of the original glands; severe is when the number of gastric glands reduced exceeds 2 / 3, with only a few glands left, or even completely disappeared.

[0185] Intestinal metaplasia: It is normal if there is no intestinal metaplasia in the gastric mucosa; it is mild if the intestinal metaplasia does not exceed 1 / 3 of the total area of ​​the glands and surface epithelium; it is moderate if the intestinal metaplasia is between 1 / 3-2 / 3 of the total area of ​​the glands and surface epithelium; it is severe if the intestinal metaplasia exceeds 2 / 3 of the total area of ​​the glands and surface epithelium.

[0186] Dysplasia: divided into low-grade and high-grade. The "Guidelines for the Diagnosis and Treatment of Chronic Gastritis in China (2022, Shanghai)" does not describe the morphological characteristics of dysplasia, and refers to the "Diagnostic Pathology by Liu Tonghua, 4th Edition" for supplementation. In low-grade dysplasia, the mucosal gland structure is mildly abnormal, the cell nuclei are long, crowded, located at the base, and the nuclear division is mild to moderate; in high-grade dysplasia, the nuclei are round or oval, the nuclear-cytoplasmic ratio is abnormal, the cell and glandular structure are obviously abnormal, the nuclear division is common, and the polarity disappears.

[0187] Atrophy and intestinal metaplasia: 0 points for absence, 3 points for mild, 6 points for moderate, and 9 points for severe; dysplasia: 0 points for absence, 3 points for low grade, and 9 points for high grade. The effects of each group on the pathological scores of the gastric mucosa in the glandular area of ​​mice are shown in Table 20.

[0188] Table 20 Pathological scores of gastric mucosal tissue in the glandular area of ​​mice in each group [M (P 25 , P 75 )]

[0189]

[0190]

[0191] As shown in Table 20, the gastric mucosal pathological scores of the H.pylori infection single factor group and the H.pylori infection combined with MNNG mutagenesis dual factor group were higher than those of the blank control group; the gastric mucosal pathological scores of the H.pylori infection combined with MNNG mutagenesis dual factor group were higher than those of the H.pylori infection single factor group. Conventionally fed mice can show CAG gastric mucosal pathological manifestations, and this CAG is a "semi-physiological" phenomenon; compared with conventional feeding methods, the single factor of H.pylori infection and the dual factor of H.pylori infection combined with MNNG mutagenesis can aggravate the degree of CAG gastric mucosal lesions in mice, and the degree of gastric mucosal lesions of H.pylori infection combined with MNNG mutagenesis dual factor is more severe, and this CAG is a pathological change. The experimental results show that there is cell senescence in the glandular gastric mucosa of the CAG mouse model, that is, the cell senescence of the twelve aging markers is correlated with CAG, and the cell senescence induced by the inflammatory effect of H.pylori infection may be involved in the occurrence and development of CAG. Xianshen Yiwei prescription has a certain dose-effect relationship in improving the pathological state of gastric mucosal tissue in the glandular area of ​​CAG mouse model.

[0192] The pathological scores of gastric mucosa tissues were as follows: the high-dose Xiancan Yiwei Formula group < the medium-dose group < the low-dose group < the CXCR2 inhibitor group < the blank model group; compared with the blank model group, the pathological scores of the glandular area gastric mucosa tissues of mice in the low-dose Xiancan Yiwei Formula group, the medium-dose Xiancan Yiwei Formula group, and the high-dose Xiancan Yiwei Formula group all decreased; compared with the blank model group, the pathological scores of the glandular area gastric mucosa tissues of mice in the medium-dose Xiancan Yiwei Formula group and the high-dose Xiancan Yiwei Formula group both decreased, and the differences were statistically significant (P = 0.011 < 0.05; P = 0.003 < 0.01), that is, both the medium-dose and high-dose Xiancan Yiwei Formula can improve the pathological state of the glandular area gastric mucosa tissues in the CAG mouse model.

[0193] 2.3 Determination of the senescent cell rate of glandular area gastric mucosa tissues in mice by SA-β-gal staining technique

[0194] Take fresh gastric mucosa tissues of mice, fix them with OCT embedding agent, prepare 4-μm frozen sections with a cryostat, and store them in a -20°C refrigerator; thaw the β-galactosidase staining kit stored in a -20°C refrigerator at room temperature, and prepare the β-galactosidase staining working solution according to the instructions of the Beyotime cell senescence β-galactosidase staining kit; let the frozen sections warm up at room temperature for 5 minutes; soak and wash the tissues with PBS buffer 3 times; add an appropriate volume of β-galactosidase staining fixative to fully cover the tissues, and fix at room temperature for no less than 15 minutes; soak and wash the tissues with PBS buffer 3 times; aspirate the PBS buffer, and add an appropriate amount of β-galactosidase staining working solution; place the sections in a wet box and incubate overnight in a 37°C incubator (without CO2); remove the staining solution on the sections and wash the tissues with PBS; then observe, mount the slides and analyze. Use Fiji ImageJ software to count the cell senescence rate in the tissues. The cell senescence rate (%) = the area of the cell senescent region in the section / the area of the tissue region in the section × 100%. The results are shown in Table 21 and Figure 1 .

[0195] Table 21 Cell senescence rate of glandular area gastric mucosa tissues in mice of each group [M(P 25 , P 75 )]

[0196]

[0197] Note: Compared with the blank model group, **P < 0.01.

[0198] From Table 21 and Figure 1It can be seen that Xianshen Yiwei Fang has a certain dose-effect relationship in delaying the senescence of gastric mucosal tissue cells in the glandular area of ​​CAG mouse model. Compared with the blank model group and the CXCR2 inhibitor group, the low-dose group, the medium-dose group and the high-dose group of Xianshen Yiwei Fang can reduce the senescence rate of gastric mucosal tissue cells in the glandular area of ​​mice; compared with the blank model group, the senescence rate of gastric mucosal tissue cells in the medium-dose group and the high-dose group of Xianshen Yiwei Fang was reduced, and the differences were statistically significant (P=0.003<0.01; P=0.003<0.01), that is, the medium-dose and high-dose Xianshen Yiwei Fang can delay the senescence of gastric mucosal tissue cells in the glandular area of ​​CAG mouse model.

[0199] 2.4 Western Blot analysis of CXCR2, p38, p53, and p21 protein expression in the gastric mucosa of the mouse glandular region

[0200] Prepare protein supernatant from the gastric mucosal tissue of the glandular region of mice, and use the prepared protein supernatant for protein immunoblotting experiments. The gastric tissue protein supernatant is balanced with lysis buffer according to the protein concentration, added to the loading buffer, and heated at 100°C for 10 minutes to denature the protein. In each lane of the gel, the total protein amount is 20-40μg, and the loading volume is between 5μL-15μL. Electrophoresis is performed at a voltage of 200V. When the bromophenol blue solution just runs out of the bottom of the gel, the electrophoresis is stopped and the membrane transfer is started. Cut the PVDF membrane into a suitable size, activate it with methanol for more than 30s, remove the gel from the glass plate, carefully cut off the excess gel at the edge, and put it into the electrotransfer clip in the order of three layers of filter paper-gel-PVDF membrane-three layers of filter paper, following the principle of "black gel and white film". Prepare the electrotransfer solution, put the electrotransfer clip into the electrotransfer box, insert the electrotransfer tank, fill the entire electrotransfer tank with the electrotransfer solution, and electrotransfer for 75 minutes at 100V. The specific time is adjusted according to the size of the target protein. After electrotransfer, the PVDF membrane was blocked with 5% skim milk powder prepared in TBST to prevent nonspecific binding. The corresponding primary antibodies CXCR2 (1:1000), p38 (1:1000), p53 (1:1000), and p21 (1:1000) were diluted with 5% skim milk powder and incubated overnight at 4°C. The primary antibody was removed the next day, and the membrane was washed three times with TBST solution for 10 minutes each time. The appropriate enzyme-labeled secondary antibody was selected according to the experimental needs, with a dilution concentration of 1:1000. The membrane was incubated on a shaker at room temperature for 1 hour, the secondary antibody was removed, and the membrane was washed three times with TBST solution for 10 minutes each time. Finally, fresh TBST was added to keep the membrane moist. ECL luminescent solution was prepared and used immediately. Automatic exposure was performed under the imaging system. If no bands appeared, try different exposure times from 5s to 2min. The expression of CXCR2, p38, p53, and p21 proteins in the glandular gastric mucosal tissue of mice was obtained, as shown in Tables 22 and Figure 2 .

[0201] Table 22 Expression of CXCR2, p38, p53 and p21 proteins in the glandular gastric mucosa of mice in each group [M(P 25 , P 75 )]

[0202]

[0203] Note: Compared with the CXCR2 inhibitor group, *P<0.05, **P<0.01.

[0204] As can be seen from Table 22, the inhibitory effect of Xianshen Yiwei Fang on the expression of CXCR2, p38, p53, and p21 proteins in the CXCR2 / p38 / p53 / p21 signaling pathway has a certain dose-effect relationship. Compared with the blank model group and the CXCR2 inhibitor group, different doses of Xianshen Yiwei Fang Chinese medicine groups can reduce the expression of CXCR2, p38, p53, and p21 proteins in the CXCR2 / p38 / p53 / p21 signaling pathway to varying degrees; compared with the blank model group and the CXCR2 inhibitor group, the expression of p53 and p21 proteins in the Xianshen Yiwei Fang Chinese medicine group were reduced, and the differences were statistically significant, that is, at the protein level, Xianshen Yiwei Fang can inhibit the CXCR2 / p38 / p53 / p21 signaling pathway by inhibiting the expression of p53 and p21 proteins. Figure 2 It can be seen that compared with the blank model group, different doses of Xianshen Yiwei prescription had different degrees of inhibitory effects on the expression of CXCR2, p38, p53, and p21 proteins in the CXCR2 / p38 / p53 / p21 signaling pathway.

[0205] In summary, it is shown that the pharmaceutical composition of the present invention has an anti-aging effect, can treat chronic atrophic gastritis by preventing and treating gastric aging, and prevent gastric precancerous lesions from transforming into gastric cancer.

[0206] 2.5 Determination of CXCR2, p38, p53, and p21 mRNA expression in the gastric mucosa of the glandular region of mice by real-time fluorescence quantitative PCR

[0207] Refer to the instructions of TaKaRa MiniBEST Universal RNA Extraction Kit for RNA extraction from mouse glandular gastric mucosa. Refer to the instructions of Rever Tra Ace qPCR RT Master Mix Kit for RNA reverse transcription. Green Realtime PCR Master Mix Kit Instructions Applied Biosystems QuantStudio 1Plus real-time fluorescence quantitative PCR system was used for PCR reaction. Mouse CXCR2, p38, p53, and p21 primer sequences (Order NO. B661302) were designed on the official website of Shanghai Bioengineering Co., Ltd. and transferred online. The PCR cycle conditions were: 95°C 60s; 40 PCR cycles (95°C 15s, 60°C 15s, 72°C 45s); melting curve analysis. Real-time fluorescence quantitative PCR reaction was performed for each sample target gene and internal reference. The real-time fluorescence quantitative PCR reaction map showed that the amplification curves of CXCR2, p38, p53, p21 genes and internal reference ACTB gene in the glandular gastric mucosa tissue of mice were smooth, and the melting curve showed a sharp single peak, indicating that the gene amplification and melting effects of the glandular gastric mucosa of mice were good. The data were obtained using 2 -△△Ct The results are shown in Table 23.

[0208] Table 23 Expression of CXCR2, p38, p53, and p21 mRNA in the glandular gastric mucosa of mice in each group [M(P 25 , P 75 )]

[0209]

[0210] Note: Compared with the blank model group, *P<0.05; compared with the CXCR2 inhibitor group, # P<0.05, ## P<0.01.

[0211] As shown in Table 23, the inhibitory effect of Xianshen Yiwei Fang on the expression of CXCR2, p38, p53, and p21 mRNA in the CXCR2 / p38 / p53 / p21 signaling pathway has a certain dose-effect relationship. Compared with the blank model group and the CXCR2 inhibitor group, the different doses of Xianshen Yiwei Fang Chinese medicine groups can reduce the expression of CXCR2, p38, p53, and p21 mRNA in the CXCR2 / p38 / p53 / p21 signaling pathway respectively; compared with the blank model group, the expression of CXCR2 mRNA in the low-dose Xianshen Yiwei Fang group, the medium-dose Xianshen Yiwei Fang group, and the high-dose Xianshen Yiwei Fang group was reduced, and the differences were statistically significant (P=0.000<0.01; P=0.004<0.01; P=0.003<0.01). 01), that is, at the gene level, Xianshen Yiwei Fang low dose, Xianshen Yiwei Fang medium dose and Xianshen Yiwei Fang high dose can inhibit CXCR2 / p38 / p53 / p21 signaling pathway by inhibiting CXCR2 mRNA expression; compared with the blank model group, the p38 mRNA expression of Xianshen Yiwei Fang low dose group and Xianshen Yiwei Fang medium dose group was decreased, and the difference was statistically significant (P=0.003<0.01; P=0.003<0.01), that is, at the gene level, Xianshen Yiwei Fang low dose and Xianshen Yiwei Fang medium ... The medium dose can inhibit the CXCR2 / p38 / p53 / p21 signaling pathway by inhibiting the expression of p38mRNA; compared with the blank model group, the p53mRNA expression of the low-dose, medium-dose and high-dose Xianshen Yiwei Fang groups was reduced, and the differences were statistically significant (P=0.001<0.01; P=0.003<0.01; P=0.048<0.05), that is, at the gene level, the low-dose, medium-dose and high-dose Xianshen Yiwei Fang groups can inhibit the CXCR2 / p38 / p53 / p21 signaling pathway by inhibiting the expression of p38mRNA. By inhibiting the expression of p53mRNA, the CXCR2 / p38 / p53 / p21 signaling pathway is inhibited; compared with the blank model group, the p21mRNA expression of the low-dose group and the medium-dose group of Xianshen Yiwei Fang was reduced, and the differences were statistically significant (P=0.003<0.01; P=0.021<0.05), that is, at the gene level, the low-dose and medium-dose Xianshen Yiwei Fang can inhibit the expression of p21mRNA, thereby inhibiting the CXCR2 / p38 / p53 / p21 signaling pathway. Therefore, the Xianshen Yiwei Fang of the present invention can prevent and treat chronic atrophic gastritis by preventing and treating gastric aging, prevent the transformation of gastric precancerous lesions to gastric cancer, and has an anti-aging effect.

[0212] In summary, the pharmaceutical composition and its application for treating chronic atrophic gastritis and precancerous lesions proposed by the present invention are scientifically and reasonably formulated. Clinical trials have shown that the pharmaceutical composition of the present invention has a definite therapeutic effect and is safe and reliable in treating CAG, can cure and significantly reduce and improve the pathological changes of gastric mucosa under gastroscopy, and can reverse and reduce the atrophy, intestinal metaplasia, dysplasia (intraepithelial neoplasia) and other pathological changes and precancerous lesions in the gastric antrum, gastric angle and gastric body of the patient. Animal experiments have made it clear that CAG is an aging-related disease, and the role of pathological factors can aggravate the cellular senescence of the glandular gastric mucosal tissue and the pathological changes of the glandular gastric mucosal tissue in the CAG mouse model; there is cellular senescence in the glandular gastric mucosal tissue of the CAG mouse model, that is, the cellular senescence of the twelve major aging markers is correlated with CAG; H. pylori infection initiates inflammatory effects-induced cellular senescence and participates in the occurrence and development of CAG; Xianshen Yiwei prescription can improve the pathological state of the glandular gastric mucosal tissue in the CAG mouse model, and Xianshen Yiwei prescription is effective in treating the CAG mouse model; Xianshen Yiwei prescription can delay the cellular senescence of the glandular gastric mucosal tissue in the CAG mouse model; Xianshen Yiwei prescription inhibits the cellular senescence-related CXCR2 / p38 / p53 / p21 signaling pathway by inhibiting the expression of p53 and p21 proteins and mRNA, thereby improving the pathological state of the CAG gastric mucosa. The pharmaceutical composition of the present invention has the effect of resisting gastric aging, can treat chronic atrophic gastritis by preventing and treating gastric aging, and prevents the transformation of gastric precancerous lesions into gastric cancer. It is a safe and efficient Chinese medicine compound preparation, which can be used in the preparation of drugs for treating chronic atrophic gastritis and precancerous lesions, and is conducive to promotion.

[0213] In summary, the Xianshen Yiwei Fang intervention of the pharmaceutical composition of the present invention can significantly reduce the risk of cancer in patients with chronic atrophic gastritis with extensive intestinal metaplasia, can prevent and treat gastric aging, prevent the transformation of gastric precancerous lesions to gastric cancer, and has an anti-aging effect. Timely use of traditional Chinese medicine intervention is of great significance for preventing the occurrence of early gastric cancer and improving the public health level.

Claims

1. A pharmaceutical composition for treating chronic atrophic gastritis and precancerous lesions, characterized in that: Including ingredients: Epimedium, Codonopsis, Alpinia oxyphylla, Poria, stir-fried Atractylodes, Sophora flavescens, vinegar-soaked Cyperus rotundus, Alpinia officinalis, Nardostachys grandiflora, vinegar-soaked Trillium, vinegar-soaked Curcuma, Prunus mume and roasted Licorice root.

2. The pharmaceutical composition for treating chronic atrophic gastritis and precancerous lesions according to claim 1, characterized in that: The invention comprises the following components in parts by weight: 1-300 parts of Epimedium, 1-300 parts of Codonopsis pilosula, 1-250 parts of Alpinia oxyphylla, 1-250 parts of Poria, 1-250 parts of stir-fried Atractylodes macrocephala, 1-200 parts of Sophora flavescens, 1-200 parts of vinegar-cured Cyperus rotundus, 1-150 parts of Alpinia officinalis, 1-150 parts of Nardostachys grandiflora, 1-120 parts of vinegar-cured Trillium, 1-120 parts of vinegar-cured Curcuma, 1-240 parts of Prunus mume and 1-120 parts of roasted Licorice root.

3. A pharmaceutical composition according to claim 1 or 2, characterized in that: The pharmaceutical composition also includes Fritillaria thunbergii and cuttlefish bone; or roasted ginger and yam; or stir-fried immature bitter orange and stir-fried radish seed; or kudzu root and roasted astragalus; or stir-fried hawthorn and chicken gizzard lining; or stir-fried Shenqu and stir-fried malt; or processed Polygala tenuifolia and stir-fried Ziziphus jujuba seeds; or Ganoderma lucidum.

4. The pharmaceutical composition according to claim 3, characterized in that According to weight, the fritillaria thunbergii 1-200 parts, cuttlefish bone 1-300 parts; the roasted ginger 1-200 parts, yam 1-300 parts; the stir-fried immature aurantium 1-200 parts, stir-fried radish seeds 1-300 parts; the kudzu root 1-300 parts, roasted astragalus 1-300 parts; the stir-fried hawthorn 1-200 parts, chicken gizzard 1-200 parts; The stir-fried Shenqu comprises 1-250 parts, stir-fried malt comprises 1-250 parts, processed Polygala tenuifolia comprises 1-200 parts, stir-fried Ziziphus jujuba seeds comprises 1-300 parts, and ganoderma lucidum comprises 1-250 parts.

5. Use of the pharmaceutical composition according to any one of claims 1 to 4 in the preparation of drugs for treating chronic atrophic gastritis and precancerous lesions.

6. The use according to claim 5, characterized in that: The pharmaceutical composition treats chronic atrophic gastritis and precancerous lesions by improving clinical symptoms, preventing the transformation of precancerous lesions into gastric cancer, and resisting aging.

7. The use according to claim 6, characterized in that: The improvement of clinical symptoms includes curing and alleviating the endoscopic gastric mucosal lesions, and reversing and improving the pathological changes of atrophy, intestinal metaplasia, and dysplasia.

8. The use according to claim 6, characterized in that: The anti-aging method is to prevent or treat chronic atrophic gastritis and precancerous lesions by inhibiting the classic anti-aging signaling pathway of CXCR2 / p38 / p53 / p21.

9. A pharmaceutical composition preparation for treating chronic atrophic gastritis and precancerous lesions, characterized in that: The pharmaceutical composition preparation comprises the pharmaceutical composition according to any one of claims 1 to 4 and / or added pharmaceutical excipients and / or added food additives.

10. A pharmaceutical composition preparation for treating chronic atrophic gastritis and precancerous lesions according to claim 9, characterized in that: The pharmaceutical composition preparation is a decoction, pill, powder, granule, ointment, pill, wine, syrup, extract, lozenge, lotion, gel, tea, suppository, koji, paste, cake, lotion, oil, thread, strip, roasting agent, smoke agent, tablet, granule, bag, oral liquid, capsule, soft capsule, pill, mixture, tincture, aerosol, enema, film or injection.

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