Spleen-tonifying and stomach-reinforcing prescription for treating precancerous lesions of gastric cancer as well as preparation method and application thereof

Abstract

The invention mainly relates to a spleen-tonifying and stomach-reinforcing prescription for treating precancerous lesions of gastric cancer as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The spleen-tonifying and stomach-benefiting formula is a traditional Chinese medicine composition, and the traditional Chinese medicine composition comprises ginseng, roasted rhizoma atractylodis macrocephalae, astragalus membranaceus, pseudo-ginseng, rhizoma zingiberis, pericarpium citri reticulatae, ginger processed pinellia, poria with hostwood, oldenlandia diffusa, vinegar-processed curcuma zedoary, lucid ganoderma and liquorice. The raw materials are subjected to water extraction to obtain the traditional Chinese medicine composition. The traditional Chinese medicine composition disclosed by the invention can relieve the stomach distension symptom and related pathological changes of precancerous lesions of gastric cancer; the overexpression of malignant progression markers DMBT1, WFDC2, CFTR, AQP5 and CLU of precancerous lesions of gastric cancer is inhibited; the phenomena of atrophy of antral antrum and gastric horn and intestinal metaplasia are relieved, precancerous lesions of gastric cancer are effectively treated, and the occurrence of gastric cancer is avoided.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and in particular relates to a spleen-strengthening and stomach-benefiting prescription for treating gastric precancerous lesions, and a preparation method and application thereof. Background Art

[0002] Gastric cancer is one of the common malignant tumors, which seriously endangers human health. Gastric precancerous lesions are an important pathological concept in the progression of gastric cancer, which refers to certain pathological changes in the gastric mucosa, which are more likely to turn into gastric cancer. Gastric mucosal cancer does not directly transform from normal cells into cancer cells, but needs to go through a multi-step process of canceration, namely chronic superficial gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → gastric cancer. The lesions that appear during this period are called precancerous lesions. Its etiology and pathogenesis have not yet been fully elucidated. It is now clear that Helicobacter pylori infection is the main cause of chronic gastritis, but other physical, chemical and biological harmful factors that act repeatedly on susceptible humans for a long time can also cause the disease. Common clinical manifestations include stomach bloating, stomach pain, indigestion and other symptoms. Gastric bleeding may also occur. Sometimes, due to the destruction of intrinsic gastric factors, vitamin B 12 Malabsorption can cause anemia. At present, gastric precancerous lesions are mainly treated with drugs, which require regular follow-up. However, drugs often have poor control effects, require surgical treatment, are difficult to completely cure, and can persist for a long time. Therefore, there is an urgent need for a drug that can effectively treat gastric precancerous lesions and improve the treatment and control effects of gastric precancerous lesions. Summary of the invention

[0003] In view of this, the object of the present invention is to provide a traditional Chinese medicine composition for treating gastric precancerous lesions. The traditional Chinese medicine composition is named Jianpi Yiwei Recipe, which can improve the bloating symptoms of gastric precancerous lesions, alleviate the pathological changes of gastric precancerous lesions, inhibit the overexpression of malignant progression markers of gastric precancerous lesions, and avoid the occurrence of gastric cancer.

[0004] The invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions. The composition comprises the following raw materials in parts by weight: 85-95 parts of ginseng, 115-125 parts of stir-fried atractylodes macrocephala, 145-155 parts of astragalus, 25-35 parts of notoginseng, 95-105 parts of dried ginger, 95-105 parts of tangerine peel, 85-95 parts of ginger pinellia, 145-155 parts of poria, 95-105 parts of oldenlandia diffusa, 85-95 parts of vinegared zedoaria, 115-125 parts of ganoderma lucidum and 95-105 parts of liquorice.

[0005] Preferably, the Chinese medicine composition comprises the following raw materials in parts by weight: 88-92 parts of ginseng, 118-122 parts of stir-fried Atractylodes macrocephala, 148-152 parts of Astragalus membranaceus, 28-32 parts of Panax notoginseng, 98-102 parts of dried ginger, 98-102 parts of tangerine peel, 88-92 parts of ginger Pinellia, 148-152 parts of Poria, 98-102 parts of Hedyotis diffusa, 88-92 parts of vinegar-curcuma, 118-122 parts of Ganoderma lucidum and 98-102 parts of licorice.

[0006] The present invention provides a method for preparing the Chinese medicine composition, comprising the following steps: Ginseng, stir-fried Atractylodes macrocephala, Astragalus membranaceus, dried ginger, tangerine peel, ginger pinellia, Poria, Hedyotis diffusa, Curcuma zedoaria, Ganoderma lucidum and licorice are mixed to obtain a mixture, the mixture is mixed with water, soaked, boiled and extracted to obtain extract 1; The Panax notoginseng was crushed and mixed with water for soaking, and then boiled and extracted to obtain extract 2; The extract 1 and the extract 2 are mixed to obtain the traditional Chinese medicine composition.

[0007] Preferably, the mass volume ratio of the mixture to water is 1 g: (8-12) mL; the mass volume ratio of Panax notoginseng to water is 1 g: (15-18) mL.

[0008] Preferably, the soaking time is 55 to 65 minutes.

[0009] Preferably, when extract 1 is obtained, the number of decoction extractions is ≥ 2 times.

[0010] Preferably, the decoction extraction is: heating to boiling and then decocting for 35 to 45 minutes.

[0011] The present invention also provides application of the Chinese medicine composition or the preparation method in preparing medicine for treating gastric precancerous lesions.

[0012] Preferably, the gastric precancerous lesions include spasmolytic polypeptide-expressing metaplasia.

[0013] Preferably, the gastric precancerous lesions include chronic atrophic gastritis.

[0014] Beneficial effects of the present invention: The invention provides a spleen-strengthening and stomach-benefiting prescription for treating gastric precancerous lesions. The spleen-strengthening and stomach-benefiting prescription is a traditional Chinese medicine composition. In the traditional Chinese medicine composition, ginseng greatly replenishes vital energy, strengthens the spleen and nourishes the stomach, astragalus is sweet and warm, replenishes qi and strengthens the spleen, and stir-fried atractylodes is sweet, bitter and warm in nature, strengthens the spleen and dries dampness to help transportation and transformation. The three are monarch drugs; tangerine peel and ginger pinellia are for regulating qi and harmonizing the stomach, relieving the middle and eliminating abdominal distension, panax notoginseng and vinegar curcuma are for promoting blood circulation and removing blood stasis, eliminating accumulation and relieving pain, and oldenlandia diffusa is for clearing away heat and detoxification, which are minister drugs; dried ginger warms the middle and dispels cold, poria strengthens the spleen and eliminates dampness and calms the mind, and ganoderma lucidum replenishes qi and nourishes the mind, which are adjuvant drugs; licorice strengthens the spleen and harmonizes the middle and harmonizes various drugs, which is a guiding drug; the whole prescription is for both tonification and purgation, cold and warming, and treating both the symptoms and the root causes, and the compatibility is rigorous, so as to play the functions of strengthening the spleen and replenishing qi, promoting blood circulation and benefiting the stomach. It is used to treat gastric precancerous lesions, can significantly reduce the bloating symptoms and related pathological changes of gastric precancerous lesions, restore chief cell-like characteristics, and significantly reduce the level of inflammatory cell infiltration; inhibit the overexpression of DMBT1, WFDC2, CFTR, AQP5 and CLU, markers of malignant progression of gastric precancerous lesions; reduce atrophy and intestinal metaplasia of the gastric antrum and gastric angle, effectively treat gastric precancerous lesions, and avoid the occurrence of gastric cancer. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 is the extracted ion current diagram of the components to be tested; wherein A is the reference substance, and B is the freeze-dried powder prepared in Example 1; wherein the blue numbers respectively represent: 1 is deacylated arginine, 2 is liquiritin, 3 is hesperidin, 4 is notoginsenoside R1, 5 is ginsenoside Re, 6 is ginsenoside Rg1, 7 is ginsenoside Rb1, 8 is ganoderic acid A, 9 is glycyrrhizic acid, 10 is astragaloside IV, 11 is 6-gingerol, 12 is atractylodes lactone II, and 13 is atractylodes lactone I.

[0016] Figure 2 The figure is a pathological diagram of the effect of the Chinese medicine composition (Jianpi Yiwei Recipe) of the present invention on preventing and treating tamoxifen-induced SPEM gastric precancerous lesions in mice; wherein, C is the control group, M is the model group, Y is the positive drug group, GL is the Jianpi Yiwei Recipe low-dose group, GM is the Jianpi Yiwei Recipe medium-dose group, and GH is the Jianpi Yiwei Recipe high-dose group.

[0017] Figure 3 Graph showing the effect of the Chinese medicine composition of the present invention on the expression of genes related to the malignant progression of SPEM gastric precancerous lesions; wherein, # indicates that compared with C, P<0.05, ## indicates that compared with C, P<0.01, * indicates that compared with M, P<0.05, ** indicates that compared with M, P<0.01; n=8, data are presented in express.

[0018] Figure 4 These are the results of gastroscopy and pathological examination of Case 1 in March 2024; from top to bottom, they are the results of gastric antral gastroscopy examination and the results of gastric antral pathological examination.

[0019] Figure 5 These are the results of gastroscopy and pathological examination of Case 1 in November 2024; from top to bottom, they are the results of gastric antral gastroscopy examination and the results of gastric antral pathological examination.

[0020] Figure 6 These are the results of gastroscopy and pathological examination of Case 2 in July 2024; from top to bottom they are: gastroscopy results of the gastric angle, pathological examination results of the gastric angle, gastroscopy results of the gastric antrum, and pathological examination results of the gastric antrum.

[0021] Figure 7 These are the results of gastroscopy and pathological examination of Case 2 in December 2024; from top to bottom they are: gastroscopy results of the gastric angle, pathological examination results of the gastric angle, gastroscopy results of the gastric antrum, and pathological examination results of the gastric antrum.

[0022] Figure 8 These are the results of gastroscopy and pathological examination of Case 3 in June 2023; from top to bottom they are: gastroscopy results of the gastric angle, pathological examination results of the gastric angle, gastroscopy results of the gastric antrum, and pathological examination results of the gastric antrum.

[0023] Fig. 9 These are the results of gastroscopy and pathological examination of Case 3 in August 2024; from top to bottom, they are the gastroscopy results of the gastric angle (left) and gastric antrum (right), and the pathological examination results of the gastric antrum. DETAILED DESCRIPTION

[0024] The invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, comprising the following raw materials in parts by weight: 85-95 parts of ginseng, 115-125 parts of stir-fried atractylodes macrocephala, 145-155 parts of astragalus, 25-35 parts of notoginseng, 95-105 parts of dried ginger, 95-105 parts of tangerine peel, 85-95 parts of ginger pinellia, 145-155 parts of poria, 95-105 parts of oldenlandia diffusa, 85-95 parts of vinegared zedoaria, 115-125 parts of ganoderma lucidum and 95-105 parts of liquorice; preferably comprising the following raw materials in parts by weight: 88-92 parts of ginseng, 118-122 parts of stir-fried atractylodes macrocephala, 148-155 parts of astragalus, 25-35 parts of notoginseng, 95-105 parts of dried ginger, 95-105 parts of dried orange peel, 85-95 parts of ginger pinellia, 145-155 parts of poria, 95-105 parts of oldenlandia diffusa, 85-95 parts of vinegared zedoaria, 115-125 parts of ganoderma lucidum and 95-105 parts of liquorice. 152 parts, 28-32 parts of Panax notoginseng, 98-102 parts of dried ginger, 98-102 parts of dried tangerine peel, 88-92 parts of ginger pinellia, 148-152 parts of Poria, 98-102 parts of white flower oldenlandia diffusa, 88-92 parts of vinegared Curcuma, 118-122 parts of Ganoderma lucidum and 98-102 parts of licorice; more preferably, the following raw materials in parts by weight: 90 parts of ginseng, 120 parts of stir-fried Atractylodes macrocephala, 150 parts of Astragalus, 30 parts of Panax notoginseng, 100 parts of dried ginger, 100 parts of dried tangerine peel, 90 parts of ginger pinellia, 150 parts of Poria, 100 parts of white flower oldenlandia diffusa, 90 parts of vinegared Curcuma, 120 parts of Ganoderma lucidum and 100 parts of licorice.

[0025] The present invention has no special limitation on the sources of the ginseng, stir-fried atractylodes, astragalus, notoginseng, dried ginger, tangerine peel, ginger pinellia, poria, oldenlandia diffusa, vinegared zedoaria, ganoderma and licorice, and conventional commercial products in the art can be used.

[0026] In the present invention, ginseng greatly replenishes vital energy, strengthens the spleen and nourishes the stomach; astragalus is sweet and warm, replenishes qi and replenishes the spleen; stir-fried white atractylodes is sweet, bitter and warm in nature, strengthens the spleen and dries dampness to help transportation and transformation; tangerine peel, ginger and pinellia regulate qi and harmonize the stomach, relieve the middle and eliminate abdominal distension; Panax notoginseng and vinegar-curcuma promote blood circulation, remove blood stasis, eliminate accumulation and relieve pain; oldenlandia diffusa clears away heat and detoxifies; dried ginger warms the middle and dispels cold; poria strengthens the spleen and eliminates dampness and calms the mind; ganoderma lucidum replenishes qi and nourishes the mind; licorice strengthens the spleen and harmonizes the middle, and harmonizes all the medicines.

[0027] The invention uses ginseng, astragalus and stir-fried atractylodes as main drugs, tangerine peel, ginger pinellia, Panax notoginseng, vinegar curcuma and oldenlandia diffusa as assistant drugs, dried ginger, poria and ganoderma lucidum as adjuvant drugs, and liquorice as a guiding drug; the whole prescription is used for both tonifying and purging, cold and warming, treating both the symptoms and the root causes, and the compatibility is rigorous, which can play the role of strengthening the spleen and replenishing qi, promoting blood circulation and benefiting the stomach. It can effectively treat gastric precancerous lesions, especially chronic atrophic gastritis.

[0028] The present invention also provides a method for preparing the Chinese medicine composition, comprising the following steps: First, mix ginseng, stir-fried atractylodes, astragalus, dried ginger, tangerine peel, ginger pinellia, poria, oldenlandia diffusa, vinegared zedoaria, ganoderma lucidum and licorice to obtain a mixture, mix the mixture with water, soak it, and boil it to extract to obtain extract 1; In the present invention, the mass volume ratio of the mixture to water is preferably 1g: (8-12) mL. In one embodiment, 1g: 8 mL, 1g: 9 mL, 1g: 10 mL, 1g: 11 mL or 1g: 12 mL can be selected. After the mixture is mixed with water, it is soaked. The soaking time is preferably 55-65 min. In one embodiment, it can be soaked for 55 min, 58 min, 60 min, 63 min or 65 min. After the mixture is soaked, it is boiled and extracted. The number of times of decoction extraction is preferably ≥ 2 times. In one embodiment, it can be boiled and extracted 2 times, 3 times or 4 times. The decoction extraction is preferably: decocted for 35-45 min after heating to boiling. In one embodiment, it can be decocted for 35 min, 38 min, 40 min, 42 min or 45 min after heating to boiling; the state of decoction after boiling is preferably a slightly boiling state. In the present invention, the decoction is poured out after each decoction and extraction, and water is added to the residue for the next decoction. After the decoction is completed, the decoctions are combined, filtered, and the filtrate is collected to obtain extract 1. The present invention does not specifically limit the filtering method, and conventional filtering methods in the art can be used.

[0029] The Panax notoginseng was crushed and mixed with water for soaking, and then boiled and extracted to obtain extract 2; In the present invention, the Panax notoginseng is preferably crushed into powder, and the powder is preferably ultrafine powder, which means that the powder can all pass through the No. 8 sieve and contains no less than 95% of the powder that can pass through the No. 9 sieve; the present invention has no special limitation on the crushing method, and the conventional crushing method in the field can be used. In one embodiment, the grinding crushing method can be selected. The crushed Panax notoginseng is mixed and soaked with water, and the mass volume ratio of Panax notoginseng to water is preferably 1g: (15~18) mL. In one embodiment, 1g: 15mL, 1g: 15.5mL, 1g: 16mL, 1g: 16.7mL, 1g: 17mL or 1g: 18mL can be selected. The soaking time is preferably 55~65min. In one embodiment, 55min, 58min, 60min, 63min or 65min can be selected. After soaking, the notoginseng is boiled and extracted. The decoction extraction is preferably: heating to boiling and then boiling for 35 to 45 minutes. In one embodiment, the boiling and then boiling can be selected to be 35 minutes, 38 minutes, 40 minutes, 42 minutes or 45 minutes; the state of the boiling and then boiling is preferably a slightly boiling state. The obtained decoction does not need to be filtered, that is, extract 2.

[0030] The extract 1 and extract 2 obtained above are mixed to obtain the Chinese medicine composition. In the present invention, after the extract 1 and extract 2 are mixed, preferably a concentration step is further included. The present invention does not specifically limit the concentration method, and a conventional concentration method in the art can be used. In one embodiment, a reduced pressure concentration method can be selected. After concentration, a thick extract is obtained, and the thick extract is preferably dried. The present invention does not specifically limit the drying method, and a conventional drying method in the art can be used. In one embodiment, a freeze-drying method can be selected to obtain a dry powder after drying.

[0031] The present invention also provides the use of the Chinese medicine composition or the preparation method in preparing a drug for treating gastric precancerous lesions. The gastric precancerous lesions preferably include spasmolytic polypeptide-expressing metaplasia.

[0032] The gastric precancerous lesions preferably also include chronic atrophic gastritis, and the chronic atrophic gastritis syndrome is characterized by spleen and stomach weakness, blood stasis blocking the collaterals, and symptoms include epigastric pain, fullness or distension, poor appetite, fatigue, etc.

[0033] The Chinese medicine composition of the present invention is used to treat gastric precancerous lesions, can significantly alleviate the bloating symptoms and pathological changes of gastric precancerous lesions, restore the characteristics of chief cells, and significantly reduce the level of inflammatory cell infiltration; inhibit the overexpression of DMBT1, WFDC2, CFTR, AQP5 and CLU, which are markers of malignant progression of gastric precancerous lesions; alleviate the atrophy and intestinal metaplasia of the gastric angle and gastric antrum, effectively treat gastric precancerous lesions, and avoid the occurrence of gastric cancer.

[0034] In the pharmaceutical application of the present invention, the drug preferably also includes pharmaceutically acceptable excipients.

[0035] In the pharmaceutical application described in the present invention, the dosage of each raw material of the Chinese medicine composition does not exceed the provisions of the pharmacopoeia standards; and the Chinese medicine composition of the present invention does not contain the 18 anti-compatibility and 19 fear incompatibility taboos, and does not contain medicinal materials marked as toxic in the legal standards and proven to be toxic by modern toxicology.

[0036] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0037] In the following embodiments, unless otherwise specified, all of them are conventional methods.

[0038] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0039] Example 1 Take 90g of ginseng, 120g of stir-fried Atractylodes macrocephala, 150g of Astragalus membranaceus, 100g of dried ginger, 100g of dried tangerine peel, 90g of ginger Pinellia tuber, 150g of Poria, 100g of Hedyotis diffusa, 90g of vinegar Curcuma, 120g of Ganoderma lucidum, and 100g of licorice, and mix the above materials to obtain a mixture.

[0040] The mixture was decocted in a Chinese medicine decoction bag, 10 times the amount of water (1 g mixture: 10 mL water) was added, and the mixture was soaked for 60 min. The mixture was heated to boiling and kept slightly boiling. After 40 min, the decoction was poured out, and 10 times the amount of water (1 g mixture: 10 mL water) was added to the residue. The mixture was heated to boiling and kept slightly boiling for 40 min. The decoction was poured out, the two decoctions were combined, filtered, and the filtrate was collected.

[0041] Weigh 30 g of Panax notoginseng, crush it into powder, add 16.7 times (500 mL) of water, soak for 60 minutes, heat to boiling and keep it slightly boiling, and mix it with the above filtrate after 40 minutes to obtain a mixed solution.

[0042] The mixed solution is concentrated under reduced pressure to a thick extract, and then freeze-dried to obtain a freeze-dried powder.

[0043] Example 2 Take 85g of ginseng, 125g of stir-fried Atractylodes macrocephala, 145g of Astragalus membranaceus, 95g of dried ginger, 105g of dried tangerine peel, 85g of ginger Pinellia tuber, 145g of Poria, 105g of Hedyotis diffusa, 85g of vinegar-curdled zedoaria, 115g of Ganoderma lucidum, and 95g of licorice, and mix the above pieces evenly to obtain a mixture.

[0044] The mixture was decocted in a Chinese medicine decoction bag, 8 times the amount of water was added, soaked for 55 minutes, heated to boiling and kept slightly boiling, the decoction liquid was poured out after 35 minutes, 11 times the amount of water was added to the residue, heated to boiling and kept slightly boiling for 42 minutes, the decoction liquid was poured out, 10 times the amount of water was added to the residue, heated to boiling and kept slightly boiling for 44 minutes, the decoction liquid was poured out. The three decoctions were combined, filtered, and the filtrate was collected.

[0045] Weigh another 25 g of Panax notoginseng, grind it into powder, add 18 times (450 mL) of water, soak for 55 min, heat to boiling and keep it slightly boiling, and mix it with the above filtrate after 35 min to obtain a mixed solution.

[0046] The mixed solution is concentrated under reduced pressure to a thick extract, and then freeze-dried to obtain a freeze-dried powder.

[0047] Example 3 Take 95g of ginseng, 115g of stir-fried Atractylodes macrocephala, 155g of Astragalus membranaceus, 105g of dried ginger, 95g of tangerine peel, 95g of ginger Pinellia tuber, 155g of Poria, 95g of Hedyotis diffusa, 95g of vinegar-curdled Atractylodes, 125g of Ganoderma lucidum, and 105g of licorice, and mix the above pieces evenly to obtain a mixture.

[0048] The mixture was decocted in a Chinese medicine decoction bag, 12 times the amount of water was added, soaked for 65 minutes, heated to boiling and kept slightly boiling, the decoction was poured out after 45 minutes, 9 times the amount of water was added to the residue, heated to boiling and kept slightly boiling for 37 minutes, the decoction was poured out, 10 times the amount of water was added to the residue, heated to boiling and kept slightly boiling for 38 minutes, the decoction was poured out, 12 times the amount of water was added to the residue, heated to boiling and kept slightly boiling for 43 minutes, the decoction was poured out. The four decoctions were combined, filtered, and the filtrate was collected.

[0049] Weigh another 35 g of Panax notoginseng, grind it into powder, add 15 times (525 mL) of water, soak for 65 minutes, heat to boiling and keep it slightly boiling, and mix it with the above filtrate after 45 minutes to obtain a mixed solution.

[0050] The mixed solution is concentrated under reduced pressure to a thick extract, and then freeze-dried to obtain a freeze-dried powder.

[0051] Test Example 1 Identification of ingredients of the Chinese medicine composition of the present invention (referred to as the spleen-strengthening and stomach-benefiting prescription) 1. Methods 1.1 Preparation of test solution and reference solution 353 g of freeze-dried powder was obtained in Example 1 of the present invention, and the yield was 28.5%. 0.1 g of freeze-dried powder prepared in Example 1 (recorded as Jianpi Yiwei Fang freeze-dried powder) was accurately weighed, 40 mL of methanol was added, the mass was weighed, ultrasonic treatment was performed for 30 min, cooled to room temperature, and the difference was made up. The supernatant was centrifuged at 10000 r / min for 15 min to obtain the test solution.

[0052] Accurately pipette appropriate amounts of deacetylcaryophylle acid, glycyrrhizin, hesperidin, notoginsenoside R1, ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, ganoderic acid A, glycyrrhizic acid, astragaloside I, 6-gingerol, atractylodes lactone II, atractylodes lactone I, germacone, dehydropachymic acid, and pachymic acid reference substances, and use chromatographic methanol to prepare single reference substance stock solutions with mass concentrations of 1.24 mg / mL, 1.13 mg / mL, 0.57 mg / mL, 1.14 mg / mL, 1.64 mg / mL, 1.72 mg / mL, 2.04 mg / mL, 2.24 mg / mL, 1.80 mg / mL, 1.15 mg / mL, 2.00 mg / mL, 1.10 mg / mL, 1.11 mg / mL, 1.08 mg / mL, 1.44 mg / mL, and 1.02 mg / mL, respectively. Accurately pipette an appropriate amount of each single reference substance stock solution to prepare a mixed reference substance solution with a mass concentration of 10 μg / mL.

[0053] 1.2 Chromatographic and mass spectrometry conditions Waters Acauity UPLC BEH C 18 Chromatographic column (100 mm × 2.1 mm, 1.7 μm); positive ion mode: 0.1% formic acid acetonitrile (A)-0.1% formic acid water (B) gradient elution; negative ion mode: 0.01% formic acid acetonitrile (A)-0.01% formic acid water (B) gradient elution. The gradient elution program for quantitative analysis is: 0-4.5 min, 8%-30% A; 4.5-9.5 min, 30%-70% A; 9.5-12.5 min, 70%-100% A; 12.5-14.0 min, 100% A. The gradient elution program for component analysis was: 0-2.5 min, 3% A; 2.5-18.0 min, 3%-48% A; 18.0-25.0 min, 48%-70% A; 25.0-28.0 min, 70%-100% A; 28.0-31.0 min, 100% A. The column temperature was 50 °C, the flow rate was 0.4 mL / min, and the injection volume was 5 μL.

[0054] Waters Xevo G2 Q-Tof mass spectrometer, ESI ion source, data acquisition in positive and negative ion modes, capillary voltage 3.0 kV (-3.0 kV), cone voltage 40 V (-40 V), ion source temperature 120 °C, desolvation temperature 550 °C, desolvation flow rate 900 L / h, scan range m / z 50~1200.

[0055] The specific quantitative ion information of quantitative analysis is: acetyl cypermethrin (negative ion mode, MH, t R =0.79min, m / z 389.1084), liquiritin (negative ion mode, MH, t R =3.02min, m / z 417.1186), hesperidin (negative ion mode, MH, t R =3.86min, m / z 609.1819), Panax notoginseng saponin R1 (negative ion mode, M+HCOO, t R =4.45min, m / z 977.5321), ginsenoside Re (negative ion mode, M+HCOO, t R =4.71min, m / z 991.5478), ginsenoside Rg1 (negative ion mode, M+HCOO, t R =4.74min, m / z 845.4899), ginsenoside Rb1 (negative ion mode, M+HCOO, t R =6.29min, m / z 1153.6006), ganoderic acid A (negative ion mode, MH, t R =6.72min, m / z 515.3009), glycyrrhizic acid (negative ion mode, MH, t R =6.84min, m / z 821.3960), astragaloside IV (negative ion mode, M+HCOO, t R =6.89min, m / z 829.4586), 6-gingerol (negative ion mode, MH, t R =7.47min, m / z 293.1753), Atractylodes lactone II (positive ion mode, M+H, t R =8.93min, m / z 233.1542), Atractylodes lactone I (positive ion mode, M+H, t R =9.65min, m / z 231.1385), Germacron (positive ion mode, M+H, t R =10.02min, m / z 219.1749), dehydropachymic acid (negative ion mode, MH, t R =11.20min, m / z 525.3580), Pachymic acid (negative ion mode, MH, t R =11.38min, m / z 527.3736).

[0056] 2. Results 2.1 Quantitative analysis system adaptability Take the mixed reference solution and test solution, and inject and measure according to the conditions of "1.2". The extracted ion chromatograms of the components to be measured in positive and negative ion modes are shown in Figure 1 The results showed that there was no obvious interference in the determination and the method had good specificity.

[0057] 2.2 Quantitative analysis results The test solution was prepared according to the method under "1.1" and 2 replicates were prepared. The samples were injected and measured under the conditions under "1.2" and the content was calculated. The results showed that the contents of the index components deacetylcaryophyllein, liquiritin, hesperidin, notoginsenoside R1, ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, ganoderic acid A, glycyrrhizic acid, astragaloside I, 6-gingerol, atractylodes lactone II and atractylodes lactone I in the freeze-dried powder of Jianpi Yiwei recipe were 0.006%, 0.323%, 1.889%, 0.112%, 0.064%, 0.619%, 0.436%, 0.032%, 0.871%, 0.024%, 0.315%, 0.002% and 0.009%, respectively.

[0058] The agreed quantitative components, germacrone, dehydropachymic acid and pachymic acid, were not detected in the lyophilized powder.

[0059] Test Example 2 The therapeutic effect of the Chinese medicine composition of the present invention on gastric precancerous lesions: Animal drug administration modeling scheme: 48 male C57BL / 6J mice were randomly divided into 6 groups: control group (C), model group (M), positive drug group (folic acid, 1.95 mg / kg, Y), Jianpi Yiwei recipe low (1.15 g / kg, GL), medium (2.3 g / kg, GM) and high dose (4.6 g / kg, GH) groups. Among them, Jianpi Yiwei recipe is the freeze-dried powder prepared in Example 1 of the present invention. Except for the control and model group mice, which were gavaged with distilled water at 0.1 mL / 10 g, the other groups were gavaged at each dose for a total of 8 days, and tamoxifen (4 g / 20 g) was injected intraperitoneally for 3 consecutive days starting from the 3rd day. High-dose tamoxifen can cause a gastric precancerous lesion model in mice with spasmolytic polypeptide-expressing metaplasia (SPEM) as the main phenotype.

[0060] On the 9th day, the mice were killed, and part of the gastric tissue was taken for pathological section observation. RNA was extracted from the other part to detect changes in the expression levels of DMBT1, GPX2, WFDC2, CFTR, AQP5 and CLU, markers of SPEM malignant progression.

[0061] Experimental results: Pathological observation results of gastric body tissue: such as HE staining of mouse gastric body pathology ( Figure 2 ), in the tamoxifen-induced mouse SPEM gastric precancerous lesion model group (M), gastric epithelial cells shed and died, and the characteristics of the chief cells at the bottom of the gastric glands disappeared, accompanied by infiltration of inflammatory cells; in the positive drug folic acid group, the infiltration of inflammatory cells was weakened, but a large number of gastric epithelial cells were still observed to die, and the characteristics of the chief cells were not restored; the high-dose group of the Jianpi Yiwei prescription could partially restore the characteristics of the chief cells and significantly reduce the level of inflammatory cell infiltration.

[0062] SPEM malignant progression marker test results: Figure 3 As shown in the results, Jianpi Yiwei recipe can effectively reduce the overexpression of DMBT1, WFDC2, CFTR, AQP5 and CLU, the malignant progression markers of SPEM gastric precancerous lesions induced by tamoxifen.

[0063] Test Example 3 Clinical trials 1. No adverse reactions have been reported in the clinical application of the Chinese medicine composition of the present invention. During the clinical application, 27 patients with gastric precancerous lesions who visited the "Shenzhen Traditional Chinese Medicine Hospital" were collected and treated with the Jianpi Yiwei Recipe for 3 months (taking the mixed solution prepared in Example 1, with a daily dose of 1 / 10 of the mixed solution in Example 1, taken twice), and the gastric bloating before and after treatment was scored, and the standards were as follows: 0: no symptoms, 1: occasional symptoms or obvious improvement, 2: symptom relief, 3: severe symptoms, and a paired rank sum test (Wilcoxon test) was performed before and after medication.

[0064] The results are shown in Table 1 below, which indicate that the Jianpi Yiwei prescription can effectively improve gastric distension in patients with gastric precancerous lesions.

[0065] 2. Typical Cases The spleen-strengthening and stomach-benefiting prescriptions used in the following cases are all mixed solutions prepared in Example 1 of the present invention, with 1 / 10 of the amount of the mixed solution prepared in Example 1 as one dose, and the method of taking is: one dose per day, divided into two doses.

[0066] Case 1: Patient Cheng, female, 33 years old, first diagnosed on March 26, 2024. Chief complaint: intermittent upper abdominal distension for more than 3 years. Gastroscopy at an external hospital 3 years ago showed: chronic atrophic gastritis, positive carbon 13 breath test, and negative reexamination after quadruple bactericidal therapy; Gastroscopy at an external hospital in 2022 showed: chronic atrophic gastritis, pathology showed: intestinal metaplasia (+), low-grade tumor-like lesions, local erosions; Gastroscopy on March 29, 2024 showed: chronic atrophic gastritis, pathology showed: chronic atrophic gastritis in the gastric antrum, mild dysplasia, inflammatory cells (2+), atrophy (2+), intestinal metaplasia (2+) in some glands, endoscopic and pathological results are shown in Figure 4 . Current symptoms: upper abdominal distension, occasional stomach pain, acid reflux, obvious after eating, nausea, good appetite, good sleep, normal bowel movements, pale red tongue, thin white fur with tooth marks, purple sublingual veins, and stringy and thin pulse. The patient has a history of "type 2 diabetes" for more than 5 years, with general blood sugar control, fasting blood sugar of 7.6mmol / L, denies other medical history, and denies family and genetic history. Western medicine diagnosis: chronic atrophic gastritis. Traditional Chinese medicine diagnosis: stomach distension, syndrome type: spleen and stomach deficiency and cold with blood stasis and depression. The treatment is to strengthen the spleen and replenish qi, activate blood circulation and benefit the stomach, supplemented by soothing the liver and regulating the spleen. Give a prescription for strengthening the spleen and benefiting the stomach. From April 2024, take the decoction of "Jianpi Yiwei Fang" for treatment, take it after breakfast and dinner, 1 dose per day. Advise the patient to keep a good mood, go out more and interact with people, eat regularly, avoid cold and raw foods, abstain from sour, sweet, and spicy foods, and avoid coffee, strong tea, alcohol, sweet potatoes, and honey; eat less soy products, beverages, and fruits, avoid barbecue, pickled products, tobacco, alcohol, and high-salt foods, avoid staying up late, and exercise appropriately. After 7 months, the patient's upper abdominal distension and acid reflux symptoms improved significantly. In October 2024, he went to the doctor and complained of no epigastric discomfort, no bloating, and no acid reflux. In November 2024, endoscopy showed: chronic atrophic gastritis, and pathology showed: chronic atrophic gastritis with erosion of the gastric antrum, mild dysplasia of local glands, inflammatory cells (2+), atrophy (1+), and intestinal metaplasia (1+). See the endoscopy and pathology results. Figure 5 The patient's antral atrophy and intestinal metaplasia were improved.

[0067] Case 2: Patient Liao, female, 46 years old, first diagnosed on August 30, 2024. Main complaint: intermittent episodes of epigastric discomfort for more than 1 year. Previous endoscopy on July 26, 2024 showed: superficial gastritis (refer to pathology, excluding atrophic gastritis C2), pathology showed: chronic atrophic gastritis in the gastric angle, mild dysplasia of local glands, inflammation (1+), atrophy (2+), intestinal metaplasia (1+); chronic atrophic gastritis in the gastric antrum, mild dysplasia of some glands (intestinal adenomatous dysplasia), inflammation (1+), atrophy (1+), intestinal metaplasia (2+), endoscopy and pathology results are shown in Figure 6. Current symptoms: epigastric discomfort, bloating, stomach pain, heartburn, hunger, no acid reflux and belching, normal appetite, good sleep, bowel movements once a day, difficult to defecate, sticky, usually emotionally unstable, normal menstruation, pale and dark tongue with tooth marks, slightly thick and greasy white fur, purple blood stasis under the tongue, and smooth pulse. Western medicine diagnosis: chronic atrophic gastritis. Chinese medicine diagnosis: epigastric pain, syndrome type: spleen and stomach deficiency, cold, blood stasis and dampness. Treatment is to strengthen the spleen and replenish qi, activate blood circulation and benefit the stomach, supplemented by soothing the liver and regulating the spleen. Give a prescription for strengthening the spleen and benefiting the stomach. From August 2024, take the decoction of "Jianpi Yiwei Fang" for treatment, take it after breakfast and dinner, 1 dose per day. Advise the patient to keep a good mood, eat regularly, avoid cold, raw, spicy, barbecued, pickled products, tobacco, alcohol, heavy salt and heavy oil foods, avoid staying up late, and exercise appropriately. Four months later, the patient's symptoms improved significantly, with no bloating, occasional epigastric discomfort, belching, acid reflux, and heartburn. On December 26, 2024, the gastroscopy showed atrophic gastritis C2 (reference pathology), and the pathology showed chronic atrophic gastritis in the gastric angle, mild reactive atypical hyperplasia of the focal glands, inflammation (1+), atrophy (1+), and intestinal metaplasia (1+), chronic atrophic gastritis in the gastric antrum, mild atypical hyperplasia of the focal glands, inflammation (1+), atrophy (1+), and intestinal metaplasia (1+). The results of gastroscopy and pathology are shown in Figure 7 The patient's gastric angle atrophy was improved, and the gastric antral intestinal metaplasia was improved.

[0068] Case 3: Patient Xu, female, 26 years old, first diagnosed on June 19, 2023. Main complaint: gastric distension for more than 2 years. Gastroscopy on June 5, 2023 showed: chronic atrophic gastritis (C2, refer to pathology) with bile reflux, pathology showed: chronic atrophic gastritis in the antrum, inflammatory cells (1+), atrophy (1+); chronic atrophic gastritis in the gastric angle, inflammatory cells (1+), atrophy (1+), gastroscopy and pathology results are shown in Figure 8 . Current symptoms: bloating, no stomach pain, belching, blood in stool, poor appetite, good sleep, no fear of cold, pale red tongue with tooth marks, thin white fur, slightly purple sublingual collaterals, thin pulse. Western medicine diagnosis: chronic atrophic gastritis. Chinese medicine diagnosis: stomach distension, syndrome type: spleen and stomach deficiency and cold with blood stasis and qi stagnation. Treatment is to strengthen the spleen and replenish qi, promote qi and activate blood circulation. Give Jianpi Yiwei Fang. From June 2023, take 35 doses of "Jianpi Yiwei Fang" decoction (about 1.5 months), take it after breakfast and dinner, 1 dose per day. Advise the patient to keep a good mood, eat regularly, avoid cold, raw, spicy, barbecue, pickled products, tobacco, alcohol, heavy salt and heavy oil food, avoid staying up late, and exercise appropriately. After more than a month, the patient's symptoms improved significantly. He reported no bloating, no stomach pain, occasional belching, no blood in the stool, good appetite, normal sleep, no fear of cold, pale red tongue with light tooth marks and thin white fur, slightly purple sublingual collaterals, and a thin pulse, so the medication was stopped. One year later, on August 3, 2024, a gastroscopy was repeated and showed: chronic atrophic gastritis (C1, refer to pathology). Pathology showed: chronic atrophic gastritis of the gastric antrum, inflammation (mild), atrophy (mild), intestinal metaplasia (mild), gastroscopy and pathology results are shown in Fig. 9 Since no obvious abnormality was found in the gastric angle, no pathology was taken in the gastric angle. The atrophy and intestinal metaplasia of the gastric angle and gastric antrum of the patient were significantly improved. The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating gastric precancerous lesions, characterized in that: The invention comprises the following raw materials in parts by weight: 85-95 parts of ginseng, 115-125 parts of stir-fried atractylodes, 145-155 parts of astragalus, 25-35 parts of notoginseng, 95-105 parts of dried ginger, 95-105 parts of tangerine peel, 85-95 parts of ginger pinellia, 145-155 parts of poria, 95-105 parts of oldenlandia diffusa, 85-95 parts of vinegar-soaked zedoaria, 115-125 parts of ganoderma lucidum and 95-105 parts of liquorice.

2. The Chinese medicine composition according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 88-92 parts of ginseng, 118-122 parts of stir-fried atractylodes, 148-152 parts of astragalus, 28-32 parts of notoginseng, 98-102 parts of dried ginger, 98-102 parts of tangerine peel, 88-92 parts of ginger pinellia, 148-152 parts of poria, 98-102 parts of oldenlandia diffusa, 88-92 parts of vinegar-soaked zedoaria, 118-122 parts of ganoderma lucidum and 98-102 parts of liquorice.

3. The method for preparing the Chinese medicine composition according to any one of claims 1 to 2, characterized in that: The following steps are involved: Ginseng, stir-fried Atractylodes macrocephala, Astragalus membranaceus, dried ginger, tangerine peel, ginger pinellia, Poria, Hedyotis diffusa, Curcuma zedoaria, Ganoderma lucidum and licorice are mixed to obtain a mixture, the mixture is mixed with water, soaked, boiled and extracted to obtain extract 1; The Panax notoginseng was crushed and mixed with water for soaking, and then boiled and extracted to obtain extract 2; The extract 1 and the extract 2 are mixed to obtain the traditional Chinese medicine composition.

4. The preparation method according to claim 3, characterized in that: The mass volume ratio of the mixture to water is 1 g: (8-12) mL, and the mass volume ratio of Panax notoginseng to water is 1 g: (15-18) mL.

5. The preparation method according to claim 3, characterized in that: The soaking time is 55 to 65 minutes.

6. The preparation method according to claim 3, characterized in that: When extract 1 is obtained, the number of decoction extractions is ≥ 2 times.

7. The preparation method according to claim 3, characterized in that: The decoction extraction comprises heating to boiling and then decocts for 35 to 45 minutes.

8. Use of the Chinese medicine composition according to any one of claims 1 to 2 or the preparation method according to any one of claims 3 to 7 in preparing a drug for treating gastric precancerous lesions.

9. The use according to claim 8, characterized in that: The gastric precancerous lesions include spasmolytic polypeptide-expressing metaplasia.

10. The use according to claim 8, characterized in that: The gastric precancerous lesions include chronic atrophic gastritis.

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