A Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, preparation method and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, belonging to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 8-15 parts of ginseng, 15-45 parts of quinquefolius, 10-30 parts of acanthopanax senticosus, 5-15 parts of fructus aurantii, 10-30 parts of trigonosciadium japonicum, 10-20 parts of zedoaria, 5-15 parts of parsley, 3-6 parts of scorpion, 3-5 parts of centipede, 10-30 parts of smilax china and 5-15 parts of roasted liquorice. The traditional Chinese medicine composition of the present invention uses ginseng, Acanthopanax senticosus and Tripterygium wilfordii as main medicines, uses Eleutherodactyla quinquefolia, Curcuma zedoaria, Paris polyphylla, Rhizoma scutellariae, Scorpio and Scolopendra subspinipes as assistant medicines, uses Fructus aurantii and Radix Glycyrrhizae Radix et Rhizoma as adjuvant medicines, and can improve the general state, body weight, gastric mucosal lesions, gastric digestive function, and expression of gastric "inflammation-cancer" transformation markers of mice with chronic atrophic gastritis and gastric precancerous lesions models, has significant therapeutic effects on chronic atrophic gastritis and gastric precancerous lesions, and has no liver and kidney toxicity.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicines, and in particular relates to a traditional Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, a preparation method and application thereof. Background Art

[0002] Chronic atrophic gastritis (CAG) with or without intestinal metaplasia (IM), dysplasia (Dys) / intraepithelial neoplasia (IN) is an important precancerous disease of the stomach, which is closely related to the occurrence of gastric cancer (GC) and is also a key stage for drug intervention. Precancerous lesions of gastric cancer (PLGC) is a pathological concept, which refers to pathological changes that are more likely to transform into cancerous tissues. The broad range includes atrophy, intestinal metaplasia, and dysplasia. Data show that the annual canceration rate of atrophy is 0.1% to 0.25%, intestinal metaplasia is 0.25%, and dysplasia is 1.36%; the 5-year cumulative incidence of gastric cancer in patients with atrophy is 0.7% to 10%, and the 5-year cumulative incidence of gastric cancer in patients with intestinal metaplasia is 5.3% to 9.8%. It can be seen that the risk of PLGC becoming cancerous increases significantly with the pathological progression, and it is prone to malignant transformation. It is a key entry point for GC prevention and control. Blocking the malignant transformation of PLGC is of great significance for the early prevention and treatment of GC.

[0003] The development of PLGC is a chronic process, with repeated illness and difficulty in radical cure. At present, the most widely used treatments for PLGC in clinical practice are drug therapy and endoscopic therapy, the overall goal of which is to remove the cause and risk factors, alleviate patient symptoms, improve the physiological function of the gastric mucosa, and reduce or delay the occurrence of gastric cancer. Eradication of Hp (Helicobacter pylori infection) is currently the main drug treatment method to block the progression of PLGC. Domestic and foreign consensus clearly recommends eradication therapy for PLGC patients infected with Hp. However, clinical studies have shown that even if Hp is eradicated, the risk of developing gastric cancer cannot be reduced in patients with PLGC in stage III / IV of the gastritis assessment system. Yu Jun et al. found that other gastric microorganisms related to persistent gastric inflammation, gastric atrophy and intestinal metaplasia still exist after Hp is eradicated. Endoscopic mucosal resection is recommended as the first choice for high-grade dysplasia of the gastric mucosa, while for low-grade dysplasia, many academic clinical guidelines recommend that patients undergo endoscopic tissue biopsy follow-up within 1 year, and endoscopic treatment should be performed when pathological changes occur in low-grade dysplasia. However, some scholars believe that low-grade dysplasia will still progress after endoscopic resection, and even postoperative anti-Helicobacter pylori treatment cannot reduce the progression rate of low-grade dysplasia. At the same time, due to factors such as medical resources, regional development, and public awareness, endoscopic technology is currently not a sufficient and effective diagnosis and treatment method. Summary of the invention

[0004] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, a preparation method and application thereof.

[0005] "All diseases are caused by spleen deficiency", spleen and stomach weakness is the initiating factor of PLGC, which runs through the disease. Due to the invasion of external evils, improper diet, or long-term illness, old age and other factors, the spleen and stomach are weak. On the basis of spleen and stomach deficiency, or due to the invasion of liver qi, the qi movement is abnormal, resulting in the spleen and stomach dysfunction, water and moisture are not transported, or stagnation and accumulation into phlegm, or internal heat, or long-term disease and stomach collateral blood stasis, qi and blood stagnation, accumulation into poison, stasis and poison are intertwined, resulting in complex and lingering disease. The transformation of gastric "inflammation-cancer" is a progressive pathological process, among which chronic non-atrophic gastritis is the beginning of the disease, the disease is in the qi, and the main pathogenesis is the stagnation of gastric qi; the "inflammation-cancer" transformation process is the development of the disease, from qi into blood, long-term disease into collaterals, from deficiency to excess, with gastric collateral stasis as the main pathogenesis, which is "the initial qi is stagnant in the meridians, and the blood is injured and enters the collaterals after a long time". The Golden Chamber states: "No evil is without poison. Heat is transformed from poison, change is caused by poison, and stasis is caused by poison." Stagnation and stasis can be transformed into poison over time. On the contrary, poison damages the blood vessels and causes blood stasis, or poison stagnates the qi and causes blood stasis, or poison consumes yin and damages yin and causes blood stasis. Stagnation is the norm, and poison is the change. Stagnation turns into poison over time, and long-term poison causes blood stasis. Stagnation and toxicity are both pathological products and new pathogenic factors. If they are not eliminated for a long time, they will promote atrophy of gastric mucosal glands, intestinal metaplasia, dysplasia, and even cancer.

[0006] The first object of the present invention is to provide a Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, wherein the Chinese medicine composition is composed of the following raw materials in parts by weight:

[0007] 8-15 parts of ginseng, 15-45 parts of quinquefolius, 10-30 parts of Acanthopanax senticosus, 5-15 parts of Citrus aurantium, 10-30 parts of Trillium, 10-20 parts of Curcuma, 5-15 parts of Paris polyphylla, 3-6 parts of scorpion, 3-5 parts of centipede, 10-30 parts of Rhizoma Cynomorii and 5-15 parts of Radix Glycyrrhizae Preparata.

[0008] Preferably, the Chinese medicine composition is composed of the following raw materials in parts by weight:

[0009] 10 parts of ginseng, 30 parts of quinquefolius, 20 parts of Acanthopanax senticosus, 10 parts of Fructus Aurantii Immaturus, 15 parts of Rhizoma Tripterygii, 15 parts of Rhizoma Curcumae, 9 parts of Rhizoma Paris, 5 parts of Scorpio, 3 parts of Scolopendra, 20 parts of Rhizoma Lophatheri and 10 parts of Radix Glycyrrhizae Preparata.

[0010] The second object of the present invention is to provide a method for preparing the above-mentioned Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, comprising the following steps:

[0011] S1. Weigh 8-15 parts of ginseng, 15-45 parts of quinquefolius, 10-30 parts of Acanthopanax senticosus, 5-15 parts of Citrus aurantium, 10-30 parts of Tripterygium wilfordii, 10-20 parts of Curcuma zedoaria, 5-15 parts of Paris polyphylla, 3-6 parts of Scorpio, 3-5 parts of Scolopendra subspinipes, 10-30 parts of Rhizoma Cynomorii and 5-15 parts of Radix Glycyrrhizae Preparata respectively, and set aside;

[0012] S2, mixing and crushing the ginseng, quinquefolius, Acanthopanax, Fructus Aurantii Immaturus, Rhizoma Curcumae, Rhizoma Paris, Rhizoma Cyperi and Radix Glycyrrhizae Preparata weighed in step S1 to obtain crushed drugs, and sieving to obtain coarse drug powder;

[0013] S3, soaking the crude drug powder obtained in step S2 in water for 1-2 hours, boiling over high heat, then decocting over low heat for 1-2 hours, filtering and separating to obtain a filter residue and a primary filtrate;

[0014] S4, adding water to the filter residue obtained in step S3, boiling for 1 to 2 hours, filtering and separating to obtain a secondary filtrate, combining the secondary filtrate with the primary filtrate to obtain a water extract;

[0015] S5, extracting the scorpion and centipede weighed in step S1 with ethanol to obtain an ethanol extract;

[0016] S6. Mix the water extract and the alcohol extract, concentrate under reduced pressure at 60-65° C. to obtain concentrated medicine, and then freeze-dry in a vacuum to obtain freeze-dried powder, i.e., the Chinese medicine composition.

[0017] Preferably, in step S2, the particle size of the crushed medicine is 2 mm, and the mesh size of the sieved mesh is 10 meshes.

[0018] Preferably, in step S3, the volume ratio of the drug powder to water is 1:10-12.

[0019] Preferably, in step S4, the volume ratio of the filter residue to water is 1:10-12.

[0020] Preferably, step S5 specifically comprises the following steps:

[0021] Add ethanol to the scorpion and centipede weighed in step S1 for reflux extraction, perform reflux extraction three times in total, each time for 0.5 h, combine the three extracts, centrifuge, take the supernatant and condense it by suspension evaporation until the ethanol is completely volatilized, and obtain an alcohol extract.

[0022] Preferably, the weight ratio of the total weight of the scorpion and centipede to the amount of ethanol added is 1:4-6.

[0023] Preferably, in step S6, the concentration of the concentrated drug is 1 to 2 g / L, the freezing temperature is -80°C or -20°C, the freezing time is 4 to 6 h or 12 to 24 h, the vacuum drying temperature is -60 to 70°C, and the vacuum drying time is 24 to 48 h.

[0024] The third object of the present invention is to provide an application of the above-mentioned Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions in the preparation of medicines for treating chronic atrophic gastritis and gastric precancerous lesions.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The traditional Chinese medicine composition provided by the invention consists of ginseng, acanthopanax, trillium, quinquefolius chinensis, zedoaria, parsley, scorpion, centipede, fructus aurantii and roasted liquorice. Ginseng is sweet and warm, is an essential medicine for all kinds of asthenia, and can greatly invigorate the spleen and lung vital energy; the acanthopanax acanthopanax can invigorate qi and strengthen the spleen, invigorate the kidney and calm the mind; the trillium can invigorate blood circulation, promote qi circulation, eliminate accumulation and disperse knots. These three medicines are the main medicines, and they are used for both attack and invigoration, and qi and blood are coordinated, and the key points of the pathogenesis of "spleen deficiency and stomach collateral stasis and toxicity" are targeted to achieve the function of strengthening the body and removing blood stasis. Five-fingered ginseng is mild in nature, replenishes qi without raising qi, replenishes qi without generating fire, supports the body without hindering evil, and strengthens the spleen without generating dryness; Curcuma zedoaria promotes qi and resolves blood, eliminates accumulation and resolves knots, and cooperates with the main drug Tripterygium wilfordii to strengthen the effect of activating blood circulation; Paris polyphylla and Rhizoma scutellariae are bitter in taste and cold in nature, and enter the liver and stomach meridians respectively, and have the functions of clearing heat and detoxifying, eliminating carbuncle and relieving pain. When used with sweet and warm tonic drugs, their warm nature can be restrained to prevent "excess qi from becoming fire"; Scorpion and Centipede are warm in nature, and have the effects of dredging meridians and relieving pain, attacking toxins and resolving knots. The above six drugs are both hard and soft, cold and warm, and support the body's deficiency and strengthen the spleen and stomach. They are all minister drugs and are used together. Citrus aurantium and licorice root are both adjuvant drugs. Citrus aurantium promotes qi and relieves distension. When qi moves, blood vessels are unobstructed, and they assist the main drug and minister drugs to strengthen the therapeutic effect. Licorice root invigorates qi and strengthens the spleen, protects the middle state, and can also harmonize the drugs.

[0027] Modern pharmacological studies have shown that ginsenoside Rg can effectively inhibit GC cell proliferation, invasion, migration and VM formation; Acanthopanax has a significant improvement on the blood rheology of blood stasis syndrome. In addition, it can also increase the secretion of peripheral blood cells CD3, CD4, and Th1 cytokines, improve the immune status of tumor patients, and has anti-fatigue, anti-inflammatory and analgesic effects, and improves the ability to tolerate hypoxia. It is suitable for a variety of chronic wasting diseases. Five-fingered hair peach, also known as five-clawed dragon, has the effects of strengthening the spleen and lungs, promoting qi and removing dampness, replenishing qi without causing fire, replenishing qi without raising qi, and supporting the body without leaving evil. It is adapted to the hot and humid climate of Lingnan, so it is called "Southern Qi". Li Dongyuan said: "When the spleen and stomach are weak, all kinds of diseases will arise." The above three herbs are sweet and warm to help yang, support the deficiency of the body and strengthen the spleen and stomach, realize the function of "the soil is in the center to irrigate the four sides", and can also provide the original yang to nourish the acquired foundation, so as to achieve the effect of strengthening the foundation and consolidating the original, taking into account the late stage of spleen deficiency involving kidney yang and patients with insufficient endowment and family history of GC.

[0028] PLGC has a lingering course of disease, and Qi deficiency lasts for a long time, and the inability to push the Qi will cause Qi stagnation, which in turn causes blood stasis. Therefore, PLGC is a process in which blood stasis gradually worsens, and there is a possibility of malignant transformation as the pathology is upgraded. However, blood must be circulated by Qi, and blood circulates when Qi moves. Therefore, the present invention uses Citrus aurantium, Trigonosciadium japonicum, and Curcuma zedoaria to break blood and promote Qi circulation, eliminate stagnation and relieve pain, and treat abdominal distension and discomfort caused by Qi stagnation. The water extract of Fructus Aurantii Immaturus can increase the expression level of 5-HT in the gastric antrum, duodenal mucosa, and jejunal mucosa, and enhance the effect of promoting gastrointestinal motility; many indicators of CAG patients, such as whole blood viscosity, plasma viscosity, red blood cell electrophoresis time, whole blood reduction viscosity, fibrinogen, and erythrocyte sedimentation equation K value, are significantly higher than those of normal patients. Curcuma Atractylodes Rhizoma can improve microcirculation, increase blood flow, resist platelet aggregation and thrombosis, improve local ischemia and hypoxia, promote inflammation absorption, ulcer healing, recovery of atrophic glands, regression of intestinal metaplasia and dysplasia, and also have a certain degree of inhibitory effect on cancer cells.

[0029] Paris polyphylla can induce GC cell autophagy and inhibit its EMT, leading to tumor cell apoptosis; Rhizoma Dioscoreae can inhibit the secretion of TGF-β1 and IL6 by GC-related fibroblasts, reverse their carcinogenic effects and reduce the proliferation, migration and invasion of AGS cells. Compendium of Materia Medica says Rhizoma Dioscoreae: "It can relieve heat and toxicity, treat carbuncle, and is used for scrofula and sores." Hp is a damp-heat external toxin that colonizes the gastric mucosa. Damp-heat and blood stasis are burning inside, and the spleen and stomach are weak and unable to heal sores and regenerate muscles. Then, rotten flesh is soaked, and blood stasis attacks the inside. Under gastroscopy, congestion, erosion and ulceration of the gastric mucosa can be seen, which is similar to the redness, swelling, heat and pain of "carbuncle". Therefore, it is a new treatment entry point to treat PLGC with heat-clearing, detoxifying and carbuncle-eliminating products from the perspective of carbuncle.

[0030] In the late stage of PLGC, dampness and turbidity accumulate and turn into heat, which enters the blood and becomes poison. The poisonous evil hurts people, is fierce and changeable, and the disease is difficult to resolve and easily turns into malignant transformation. Therefore, toxic insect drugs are often used to attack poison and dissipate knots, break blood stasis and eliminate hardness, and relieve pain. Professor Lao Shaoxian, a famous spleen and stomach disease expert in my country, is good at using blood-activating and blood-breaking products such as scorpions and leeches to treat moderate and severe dysplasia of gastric mucosa. "Medical Zhongzhong Canxi Lu" says: "Scorpions, although poisonous in nature, are good at detoxification and eliminate all sores. They are combined with centipedes as medicines, and their strengths complement each other." Scorpions and centipedes are often used as medicine pairs to attack poison, inhibit tumors and relieve pain, and are clinical broad-spectrum anticancer drugs. Therefore, the present invention uses a turbidity-clearing and detoxification prescription with scorpions and centipedes as the basic medicine to treat PLGC patients with turbidity and toxicity syndrome, which can reduce the expression of HIF-1α and VEGF in the gastric mucosa to resist angiogenesis, and promote gastric mucosal repair and absorption of vitamin B12 to improve anemia.

[0031] The Chinese medicine composition of the present invention fully considers the physiological characteristics of the spleen and stomach and the pathological characteristics of PLGC, follows the principle of "treating the middle jiao like a balance, it cannot be lifted unless it is balanced", takes both deficiency and excess into consideration, combines hardness and softness, and adjusts the cold and heat, and regulates qi and blood, and targets the pathogenesis of spleen deficiency and stomach collateral stasis and toxicity, so as to achieve the functions of strengthening the body and replenishing qi, removing blood stasis and unblocking collaterals, and detoxifying and eliminating accumulation. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is a graph showing the changes in mouse body weight from 1 to 14 weeks of drug administration;

[0033] in, Figure 1 A is a graph showing the weight change trend of mice from 1 to 14 weeks after administration; Figure 1 B is the weight changes of mice in each group; Figure 1 C is a comparison of the body weight of mice in each group at 14 weeks (compared with the model control group, ** P<0.01, *** P < 0.001, **** P<0.0001);

[0034] Figure 2 This is a comparison of the gastric mucosal morphology of mice in each group after 14 weeks of administration;

[0035] Figure 3 HE staining and AB-PAS staining of mice after 14 weeks of drug administration;

[0036] Figure 4 The expression levels of serum gastric digestive enzyme PGⅠ and PGⅡ and their ratio PGR and G-17 in each group of mice after 14 weeks of administration;

[0037] in, Figure 4 A is the expression level of serum gastric digestive zymogen PGⅠ in mice of each group; Figure 4 B is the expression level of serum gastric digestive zymogen PGⅡ in mice of each group; Figure 4 C is the PGR ratio of mice in each group; Figure 4 D is the expression of G-17 in each group of mice (compared with the model control group, * P<0.05, ** P<0.01, *** P < 0.001, **** P<0.0001, n=4);

[0038] Figure 5 is the expression level of MTL and PGE2 in the serum of each group of mice after 14 weeks of administration;

[0039] in, Figure 5 A is the serum MTL expression level of mice in each group; Figure 5 B is the expression level of serum PGE2 in each group of mice (compared with the model control group, * P<0.05, ** P<0.01, *** P < 0.001, **** P<0.0001, n=4);

[0040] Figure 6 is the expression level of IL-6, IL-1β, and TNF-α in the serum of each group of mice after 14 weeks of administration;

[0041] in, Figure 6 A is the expression level of serum IL-6 in each group of mice; Figure 6 B is the expression level of serum IL-1β in each group of mice; Figure 6 C is the expression level of TNF-α in the serum of each group of mice (compared with the model control group, ** P<0.01, *** P < 0.001, **** P<0.0001, n=4);

[0042] Figure 7 is the relative mRNA expression level of CDX2, MUC2, KLF4, and Villin1 in the gastric mucosa of mice after 14 weeks of administration;

[0043] in, Figure 7 A is the relative expression level of CDX2 mRNA in mouse gastric mucosa; Figure 7 B is the relative expression level of MUC2 mRNA in mouse gastric mucosa; Figure 7 C is the relative expression level of KLF4 mRNA in mouse gastric mucosa; Figure 7 D is the relative expression level of Villin1 mRNA in gastric mucosa of mice (compared with the model control group, * P<0.05, ** P<0.01, *** P < 0.001, ****P<0.0001, n=6);

[0044] Figure 8 The protein expression levels of MUC2 and Villin1 in the gastric mucosa of mice after 14 weeks of administration;

[0045] In the figure, protein expression of MUC2 and Villin1 in gastric mucosal tissue of mice in each group (immunohistochemistry, 100×, scale bar 100 μm);

[0046] Fig. 9 The mRNA expression levels of VEGF, E-cad, Vimentin, and N-cad in the gastric mucosa of mice after 14 weeks of administration;

[0047] in, Fig. 9 A is the mRNA expression level of VEGF in mouse gastric mucosa; Fig. 9 B is the relative level of E-cad mRNA in mouse gastric mucosa; Fig. 9 C is the mRNA expression level of Vimentin in mouse gastric mucosa; Fig. 9 D is the mRNA expression level of N-cad in gastric mucosa of mice (compared with the model control group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, n=6);

[0048] Fig.10 The protein expression levels of VEGF, E-cad, and N-cad in the gastric mucosa of mice after 14 weeks of administration;

[0049] In the figure, the protein expressions of VEGF, E-cad, and N-cad in the gastric mucosal tissues of mice in each group (immunohistochemistry, 100×, scale bar 100 μm);

[0050] Fig.11 is the relative mRNA expression level of HER2, TP53, and Ki67 in the gastric mucosa of mice after 14 weeks of administration;

[0051] in, Fig.11 A is the relative expression level of HER2 mRNA in mouse gastric mucosa; Fig.11 B is the relative expression level of TP53 mRNA in mouse gastric mucosa; Fig.11 C is the relative expression level of Ki67 mRNA in mouse gastric mucosa (compared with the model control group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, n=6);

[0052] Fig.12 The expression levels of serum AST, ALT, CRE, and Urea in each group of mice after 14 weeks of administration;

[0053] in, Fig.12 A is the AST level of body weight of mice in each group; Fig.12 B is the ALT level of body weight of mice in each group; Fig.12 C is the CRE level of the body weight of mice in each group; Fig.12 D is the Urea level of body weight of mice in each group (compared with the model control group, **P<0.01, ***P<0.001, ****P<0.0001, n-6). DETAILED DESCRIPTION

[0054] The following is a description of the embodiments of the present invention. Figures 1 to 12 , the technical solutions in the embodiments of the present invention are clearly and completely described. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0055] Example 1

[0056] The embodiment of the present invention provides a traditional Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, wherein the traditional Chinese medicine composition is composed of the following raw materials in parts by weight:

[0057] 10 parts of ginseng, 30 parts of quinquefolius, 20 parts of Acanthopanax senticosus, 10 parts of Fructus Aurantii Immaturus, 15 parts of Rhizoma Tripterygii, 15 parts of Rhizoma Curcumae, 9 parts of Rhizoma Paris, 5 parts of Scorpio, 3 parts of Scolopendra, 20 parts of Rhizoma Lophatheri and 10 parts of Radix Glycyrrhizae Preparata.

[0058] The present invention also provides a method for preparing the above-mentioned Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, which specifically comprises the following steps:

[0059] S1. Weigh 10 parts of ginseng, 30 parts of quinquefolius, 20 parts of Acanthopanax senticosus, 10 parts of Citrus aurantium, 15 parts of Tripterygium wilfordii, 15 parts of Curcuma zedoaria, 9 parts of Paris polyphylla, 5 parts of Scorpio, 3 parts of Scolopendra subspinipes, 20 parts of Rhizoma Cynomorii and 10 parts of Radix Glycyrrhizae Preparata respectively and set aside;

[0060] S2, mixing and grinding the ginseng, quinquefolius, Acanthopanax, Fructus Aurantii Immaturus, Rhizoma Curcumae, Rhizoma Paris, Rhizoma Cyperi and Radix Glycyrrhizae Preparata weighed in step S1 to a diameter of 2 mm, and then filtering through a 10-mesh sieve to obtain a coarse drug powder;

[0061] S3, soaking the crude drug powder obtained in step S2 in water for 1 hour, boiling over high heat, then decocting over low heat for 1 hour, filtering and separating to obtain a filter residue and a primary filtrate;

[0062] The volume ratio of the drug powder to water is 1:10;

[0063] S4, adding water to the filter residue obtained in step S3, boiling for 1 hour, filtering and separating to obtain a secondary filtrate, combining the secondary filtrate with the primary filtrate to obtain a water extract;

[0064] The volume ratio of the filter residue to water is 1:10;

[0065] S5, extracting the scorpion and centipede weighed in step S1 by ethanol to obtain an alcohol extract, specifically comprising the following steps:

[0066] Add 60% ethanol to the scorpion and centipede weighed in step S1 for reflux extraction, perform reflux extraction three times in total, each reflux extraction for 0.5 h, combine the three extracts, centrifuge, and take the supernatant for suspension evaporation and concentration until the ethanol is completely volatilized to obtain an alcohol extract;

[0067] The weight ratio of the total weight of the scorpion and the centipede to the amount of ethanol added is 1:4;

[0068] S6. Mix the water extract and the alcohol extract, concentrate under reduced pressure at 60°C to 1 g / L, freeze at -20°C overnight, and then vacuum dry at -60°C for 48 hours to obtain a freeze-dried powder, i.e., the Chinese medicine composition.

[0069] Example 2

[0070] The embodiment of the present invention provides a traditional Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, wherein the traditional Chinese medicine composition is composed of the following raw materials in parts by weight:

[0071] 8 parts of ginseng, 45 parts of quinquefolius, 10 parts of Acanthopanax senticosus, 15 parts of Fructus Aurantii Immaturus, 10 parts of Rhizoma Tripterygii, 20 parts of Rhizoma Curcumae, 5 parts of Rhizoma Paris, 6 parts of Scorpio, 3 parts of Scolopendra, 30 parts of Rhizoma Lophatheri and 5 parts of Radix Glycyrrhizae Preparata.

[0072] The present invention also provides a method for preparing the above-mentioned Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, which specifically comprises the following steps:

[0073] S1. Weigh 8 parts of ginseng, 45 parts of quinquefolius, 10 parts of Acanthopanax senticosus, 15 parts of Citrus aurantium, 10 parts of Tripterygium wilfordii, 20 parts of Curcuma zedoaria, 5 parts of Paris polyphylla, 6 parts of Scorpio, 3 parts of Scolopendra subspinipes, 30 parts of Rhizoma Cynomorii and 5 parts of Radix Glycyrrhizae Preparata respectively and set aside;

[0074] S2, mixing and grinding the ginseng, quinquefolius, Acanthopanax, Fructus Aurantii Immaturus, Rhizoma Curcumae, Rhizoma Paris, Rhizoma Cyperi and Radix Glycyrrhizae Preparata weighed in step S1 to a diameter of 2 mm, and then filtering through a 10-mesh sieve to obtain a coarse drug powder;

[0075] S3, soaking the crude drug powder obtained in step S2 in water for 2 hours, boiling over high heat, then decocting over low heat for 2 hours, filtering and separating to obtain a filter residue and a primary filtrate;

[0076] The volume ratio of the drug powder to water is 1:12;

[0077] S4, adding water to the filter residue obtained in step S3, boiling for 2 hours, filtering and separating to obtain a secondary filtrate, combining the secondary filtrate with the primary filtrate to obtain a water extract;

[0078] The volume ratio of the filter residue to water is 1:12;

[0079] S5, extracting the scorpion and centipede weighed in step S1 by ethanol to obtain an alcohol extract, specifically comprising the following steps:

[0080] Add 60% ethanol to the scorpion and centipede weighed in step S1 for reflux extraction, perform reflux extraction three times in total, each reflux extraction for 0.5 h, combine the three extracts, centrifuge, and take the supernatant for suspension evaporation and concentration until the ethanol is completely volatilized to obtain an alcohol extract;

[0081] The weight ratio of the total weight of the scorpion and the centipede to the amount of ethanol added is 1:6;

[0082] S6. Mix the water extract and the alcohol extract, concentrate under reduced pressure at 65°C to 2 g / L, then freeze at -80°C for 4 hours, and then vacuum dry at 70°C for 24 hours to obtain a freeze-dried powder, i.e., the Chinese medicine composition.

[0083] Example 3

[0084] The embodiment of the present invention provides a traditional Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, wherein the traditional Chinese medicine composition is composed of the following raw materials in parts by weight:

[0085] 15 parts of ginseng, 15 parts of quinquefolius, 30 parts of Acanthopanax senticosus, 5 parts of Fructus Aurantii Immaturus, 30 parts of Rhizoma Tripterygii, 10 parts of Rhizoma Curcumae, 15 parts of Rhizoma Paris, 3 parts of Scorpio, 5 parts of Scolopendra, 10 parts of Rhizoma Lycopodiellae and 15 parts of Radix Glycyrrhizae Preparata.

[0086] The present invention also provides a method for preparing the above-mentioned Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, which specifically comprises the following steps:

[0087] S1. Weigh 15 parts of ginseng, 15 parts of quinquefolius, 30 parts of Acanthopanax senticosus, 5 parts of Citrus aurantium, 30 parts of Tripterygium wilfordii, 10 parts of Curcuma zedoaria, 15 parts of Paris polyphylla, 3 parts of Scorpio, 5 parts of Scolopendra subspinipes, 10 parts of Rhizoma Cynomorii and 15 parts of Radix Glycyrrhizae Preparata respectively and set aside;

[0088] S2, mixing and grinding the ginseng, quinquefolius, Acanthopanax, Fructus Aurantii Immaturus, Rhizoma Curcumae, Rhizoma Paris, Rhizoma Cyperi and Radix Glycyrrhizae Preparata weighed in step S1 to a diameter of 2 mm, and then filtering through a 10-mesh sieve to obtain a coarse drug powder;

[0089] S3, soaking the crude drug powder obtained in step S2 in water for 2 hours, boiling over high heat, then decocting over low heat for 2 hours, filtering and separating to obtain a filter residue and a primary filtrate;

[0090] The volume ratio of the drug powder to water is 1:11;

[0091] S4, adding water to the filter residue obtained in step S3, boiling for 2 hours, filtering and separating to obtain a secondary filtrate, combining the secondary filtrate with the primary filtrate to obtain a water extract;

[0092] The volume ratio of the filter residue to water is 1:11;

[0093] S5, extracting the scorpion and centipede weighed in step S1 by ethanol to obtain an alcohol extract, specifically comprising the following steps:

[0094] Add 60% ethanol to the scorpion and centipede weighed in step S1 for reflux extraction, perform reflux extraction three times in total, each reflux extraction for 0.5 h, combine the three extracts, centrifuge, and take the supernatant for suspension evaporation and concentration until the ethanol is completely volatilized to obtain an alcohol extract;

[0095] The weight ratio of the total weight of the scorpion and the centipede to the amount of ethanol added is 1:5;

[0096] S6. Mix the water extract and the alcohol extract, concentrate under reduced pressure at 60°C to 1.5 g / L, then freeze at -80°C for 6 hours, and then vacuum dry at 25°C for 30 hours to obtain a freeze-dried powder, i.e., the Chinese medicine composition.

[0097] Since the effects of the Chinese medicine compositions for treating chronic atrophic gastritis and gastric precancerous lesions provided in Examples 1 to 3 of the present invention are basically the same, only the efficacy of the Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions provided in Example 1 of the present invention is analyzed and verified below.

[0098] 1. Establishment of PLGC mouse model and experimental design

[0099] The PLGC mouse model was established by free drinking combined with hunger and satiety disorder method using N-methyl-N-nitrosourea (MNU) method. The male C57BL / 6 mice were judged to be successful in modeling by observing the whole body state, weight changes and gastric mucosal pathology. After the modeling was successful, 50 model group mice at this pathological stage and 8 blank group mice of the corresponding age were randomly selected for efficacy study. The blank group mice were the blank control group (Control); the model group mice were randomly divided into 5 groups: model control group (Model), positive control group (FA), low-dose Chinese medicine group (FTJE-L), medium-dose Chinese medicine group (FTJE-M), and high-dose Chinese medicine group (FTJE-H), with 10 mice in each group. The specific design of each group of mice is as follows:

[0100] Blank control group (Control): Blank mice continued to drink normal drinking water and were given normal saline by gavage once a day for 14 weeks;

[0101] Model control group (Model): The mice in the model group continued to drink 150 μg / mL MNU modeling solution and were given normal saline by gavage once a day for 14 weeks;

[0102] Positive control group (FA): The mice in the model group continued to drink 150 μg / mL MNU modeling solution and were given folic acid 1.95 mg / kg·d by gavage once a day for 14 weeks;

[0103] Low-dose Chinese medicine group (FTJE-L): The mice in the model group continued to drink 150 μg / mL of MNU modeling solution, and were given 9.56 g / kg·d of the Chinese medicine composition of Example 1 of the present invention by gavage, once a day, for a total of 14 weeks;

[0104] Medium dose group of traditional Chinese medicine (FTJE-M): The mice in the model group continued to drink 150 μg / mL of MNU modeling solution, and were given 19.11 g / kg·d of the traditional Chinese medicine composition of Example 1 of the present invention by oral gavage, once a day, for a total of 14 weeks;

[0105] Traditional Chinese medicine high-dose group (FTJE-H): The mice in the model group continued to drink 150 μg / mL of MNU modeling solution, and were given 38.22 g / kg·d of the traditional Chinese medicine composition of Example 1 of the present invention by gavage, once a day, for a total of 14 weeks;

[0106] After 14 weeks of treatment, the general state and weight changes of the mice in each group were observed. The pathological changes of gastric mucosal tissue of the mice were evaluated by HE staining and AB-PAS staining. The expression levels of PG I, PGII, Gas-17, PGE2, MTL, TNF-α, IL-1β, and IL-6 in the serum of the mice were detected by ELISA. The expression levels of intestinal metaplasia, dysplasia, and tumor markers were detected by qPCR and / or immunohistochemistry. The therapeutic effect of FTJF on the MNU-induced PLGC mouse model was evaluated in many aspects. The expression levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE), and urea (Urea) in the serum samples of each group of mice were detected by an automatic biochemical analyzer to clarify the effect of FTJF on the liver and kidney function of the PLGC mouse model.

[0107] II. Intervention effect of the Chinese medicine composition provided in Example 1 of the present invention on the PLGC mouse model

[0108] 1. Observation of the whole body condition

[0109] During the intervention period, naked eye observation showed that the mice in the blank control group were in good mental state, agile, with smooth and shiny hair, white teeth, normal and light pink nails, auricles and limbs, moderate body shape, strong appetite, scrambled for food when fed, and drank water continuously during feeding; the mice in the modeling control group were listless, slow to react, slow to move, with gray and fluffy hair, yellow teeth, white nails, auricles and limbs, thin body shape, reduced appetite, and dislike of drinking water; the general condition of mice in each dose group of Chinese medicine and the positive control group was improved.

[0110] 2. Body weight changes of mice in each group

[0111] like Figure 1 As shown in A and Table 1 below, during the 14-week drug intervention, the weight of mice in the blank control group continued to increase, the weight of mice in the model control group gradually decreased, and the weight of mice in each dose group of Chinese medicine and the positive control group slowly decreased and then gradually increased. Figure 1 B is the difference in weight change of mice in each group. Figure 1 B analysis showed that body weight increased after drug intervention, and the Chinese medicine dose groups were better than the folic acid group. Figure 1 C is the weight change result of the 14th week of administration compared with the 1st week of administration. Figure 1 C The results showed that body weight increased after drug intervention, and the Chinese medicine dose groups were better than the folic acid group.

[0112] Table 1 Body weight and body weight changes of mice after administration for 1-14 weeks (x±s)

[0113]

[0114] 3. Comparison of gastric mucosal morphology of mice in each group

[0115] like Figure 2 As shown in the figure, it can be seen by naked eye that the gastric mucosa of the glandular stomach of the blank control group mice is dark red, the mucosa is smooth and shiny, and the mucosal folds are regularly arranged. The gastric mucosa of the forestomach is thinner, light pink, smooth, and the folds are neatly arranged. The ratio of the anterior and posterior stomach is about 1:2. In the gastric mucosa of the model control group mice, the gastric mucosa of the glandular stomach is light pink, the local mucosa is whitish, the glossiness is poor, the mucosal folds are reduced, the gastric mucosa of the forestomach is thickened, grayish white, accompanied by bile yellow staining, the surface is rough, there are granular protrusions, the mucosal folds disappear, the ratio of the anterior and posterior stomach is about 2:1, and the edges are unclear. The color, glossiness, and fold arrangement of the gastric mucosa of the mice in each drug group and the positive control group were improved, and the improvement of the gastric mucosa of the mice in the high-dose Chinese medicine group was the most obvious.

[0116] 4. Pathological changes of gastric mucosa in mice of each group

[0117] like Figure 3As shown in the figure, under HE staining, the pathological sections of the gastric mucosa of mice in the blank control group showed uniform thickness of each layer of the mucosa, neat cell structure, clear layers, regular shape, regular and tight arrangement of epithelial cells, intact polarity of cells and nuclei, and no capillary dilation. The pathological sections of the gastric mucosa of mice in the model control group showed disordered glandular hierarchy, obvious thickening of the basement membrane, visible inflammatory cell infiltration, obvious vacuolar changes of cells, mucus lakes of varying sizes formed in the glandular cavity, showing moderate to severe intestinal metaplasia, part of the mucosa was serrated or U-shaped, and two or more single-layer epithelial cells in the glandular cavity became multi-layer irregularly arranged cell clusters without luminal structure, showing tissue atypia. Compared with the model control group, the positive control group and each dose group of Chinese medicine had a milder degree of lesions.

[0118] pass Figure 3 It can be seen that under AB-PAS staining, at 22 weeks, the pathological sections of the gastric mucosa of the mice in the blank group showed red staining of the mucosal layer, and no obvious blue staining foci were observed, which were glands that secreted neutral mucus. The glands in the pathological sections of the gastric mucosa of the mice in the model control group were stained dark blue, indicating that there were intestinal metaplastic glands that secreted acidic mucus, which was consistent with the intestinal metaplasia of PLGC. After intervention in the positive drug group, the intestinal metaplasia of the gastric mucosa of the mice did not improve significantly. After FTJF intervention, the intestinal metaplasia of the gastric mucosa of the mice in each dose group of Chinese medicine was improved, among which the improvement in the high dose group was the most obvious.

[0119] 5. Expression of serum gastric digestive enzyme PGⅠ, PGⅡ and G-17 in each group of mice

[0120] The expression levels of serum gastric digestive enzymes PGⅠ and PGⅡ in each group of mice were detected by ELISA, and the PGR (PGⅠ / PGⅡ) of mice was calculated. At the same time, the expression of gastrin 17 (G-17) was also detected to evaluate the atrophy of each group of mice. Figure 4 AD shows that compared with the blank control group, the serum PGⅠ level of mice in the model control group decreased, the PGⅡ level increased, the ratio PGR decreased, and the G-17 level increased. The results were statistically significant. Figure 3The HE staining results indicate that the PLGC pathological model mice constructed by the MNU modeling agent combined with the hunger and satiety disorder method have atrophic lesions. At the same time, it can be seen from the results of Table 2 that after the intervention of the Chinese medicine composition of Example 1 of the present invention, compared with the model control group, the serum PGⅠ level of the mice in the positive control group and each dose group of Chinese medicine recovered, and the difference was not statistically significant; the PGⅡ level of the positive control group and each dose group of Chinese medicine decreased compared with the model control group, and the PGR ratio was also reduced, and the results were statistically different; and the G-17 level of the positive control group and each dose group of Chinese medicine decreased compared with the model control group, and the results of the other groups except the low-dose group of Chinese medicine were statistically different, indicating that the Chinese medicine composition of Example 1 of the present invention can play a role in treating and improving atrophic pathological changes by downregulating the PGⅡ and G-17 levels in the serum of PLGC mice and restoring normal PGR and G-17 levels.

[0121] Table 2 Expression of serum gastric digestive enzyme PGⅠ, PGⅡ, G-17 in mice of each group [x±s or M(P 25 ,M 75 )]

[0122]

[0123]

[0124] 6. Expression levels of serum motilin and prostaglandin E2 in each group of mice

[0125] The expression levels of serum motilin (MTL) and prostaglandin E2 (PGE2) in each group of mice were detected by ELISA to evaluate the gastric function of each group of mice. Figure 5 As shown in Table 3 below, Figure 5 As can be seen from Table 3 below, compared with the blank control group, the expression level of serum PGE2 in the model control group mice was increased, and the expression level of MTL was decreased, and the results were statistically significant. After the intervention of the Chinese medicine composition of Example 1 of the present invention, compared with the model control group, the expression level of serum PGE2 in the positive control group and each dose group of Chinese medicine mice was decreased, and the expression level of MTL was increased, indicating that the Chinese medicine composition of Example 1 of the present invention may affect the hormone level in mice through certain pathways, thereby improving gastric function.

[0126] Table 3 Expression levels of serum MTL and PGE2 in mice of each group (x±s or M (P 25 ,M 75 ))

[0127]

[0128] 7. Expression levels of IL-6, IL-1β, and TNF-α in the serum of mice in each group

[0129] The expression levels of serum interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α) in each group of rats were detected by ELISA to evaluate the inflammatory conditions of each group of mice. The test results are shown in Figure 6 As shown in Table 4 below, Figure 6 As can be seen from Table 4 below, compared with the blank control group, the expression levels of IL-1β, IL-6, and TNF-α in the serum of the mice in the model control group were significantly increased, while the expression levels of IL-1β, IL-6, and TNF-α in the serum of the mice in the positive control group and the mice intervened with the Chinese medicine composition of Example 1 of the present invention were reduced, indicating that folic acid and the Chinese medicine composition of Example 1 of the present invention can reduce the gastric mucosal inflammatory response of the PLGC mouse model by down-regulating the expression levels of inflammatory factors IL-1β, IL-6 and TNF-α in the serum, and the effect of the Chinese medicine composition of Example 1 of the present invention on reducing the expression levels of IL-6 and TNF-α in the serum of the model mice is better than folic acid, and is dose-dependent.

[0130] Table 4 Expression levels of IL-6, IL-1β and TNF-α in the serum of mice in each group

[0131]

[0132] 7. Expression levels of CDX2, MUC2, KLF4, and Villin1, the gastric mucosal intestinal metaplasia markers in each group of mice

[0133] The mRNA expression levels of CDX2, MUC2, KLF4, and Villin1 in the gastric mucosa of each group of mice were detected by RT-qPCR. The test results are shown in Figure 7 As shown in Table 5 below, Figure 7 As can be seen from Table 5 below, the mRNA levels of CDX2, KLF4, MUC2, and Villi1n1 in the gastric mucosa of mice in the model control group were all increased, while the above intestinal metaplasia markers in the gastric mucosa of mice intervened by the Chinese medicine composition of Example 1 of the present invention were significantly lower than those in the model control group.

[0134] Table 5 mRNA expression levels of CDX2, KLF4, MUC2, and VILLIN in mouse gastric mucosa (x±s)

[0135]

[0136] At the same time, immunohistochemistry was used to detect the protein expression of MUC2 and Villin in the gastric mucosa of each group of mice. Figure 8 As shown, through Figure 8 It can be seen that the gastric mucosa of the blank group mice of the two groups of proteins was uniformly light yellow, without obvious brown-yellow particles; the model group was significantly darker than the blank group, and the protein positive expression appeared as brown-yellow particles, mainly yellow cytoplasm, some of which were darker, mostly located in the IM area; the positive control group had no significant change in color compared with the model group; the protein positive expression of each Chinese medicine treatment group decreased, and the expression reduction became more obvious with the increase of dose.

[0137] The experimental results indicate that the Chinese medicine composition of Example 1 of the present invention can improve the pathological condition of intestinal metaplasia by down-regulating the intestinal metaplasia markers of the gastric mucosa of PLGC model mice.

[0138] 9. Expression levels of gastric mucosal dysplasia markers VEGF, Vimentin, E-cad, and N-cad in each group of mice

[0139] The mRNA expression levels of VEGF, Vimentin, E-cad, and N-cad in the gastric mucosa of each group of mice were detected by RT-qPCR technology. The test results are as follows Fig. 9 As shown in Table 6 below, Fig. 9 As can be seen from the results in Table 6 below, at the mRNA expression level, the expression levels of gastric mucosal dysplasia markers VEGF, Vimentin, and N-cad in the model control group mice were all increased, while the expression level of E-cad was reduced. After the intervention of the Chinese medicine composition of Example 1 of the present invention, the expression levels of gastric mucosal dysplasia markers VEGF, Vimentin, and N-cad in the mice in each treatment group of the Chinese medicine were reduced, while the expression level of E-cad was increased, and the results were statistically significant.

[0140] Table 6 mRNA expression levels of VEGF, E-cad, N-cad and Vimentin in mouse gastric mucosa

[0141]

[0142] At the same time, immunohistochemistry was used to detect the protein expression of VEGF, E-cad, and N-cad in the gastric mucosa of each group of mice. Fig.10 As shown, through Fig.10The results show that, in terms of protein expression level, the protein expression levels of gastric mucosal dysplasia markers VEGF and N-cad in the model control group were significantly higher than those in the blank control group, showing brown-yellow granular coloration, and the cytoplasm was darker. After positive drug treatment, the positive area of ​​gastric mucosal dysplasia marker VEGF protein in mice decreased, but the N-cad protein level showed an increased expression. After intervention with each dose group of the Chinese medicine composition of Example 1 of the present invention, the protein positive area and staining intensity of gastric mucosal dysplasia markers VEGF and N-cad in mice were reduced, and the medium and high dose groups were more obvious. The expression of E-cad protein in the gastric mucosa of mice in the model control group was significantly lower than that in the blank control group, with reduced brown-yellow granular coloration and insignificant cytoplasmic coloration. After intervention with positive drugs and each dose group of Chinese medicine, the positive area of ​​E-cad protein increased, and each dose group of Chinese medicine was superior to the positive drug group, and up-regulated the expression of E-cad protein in a dose-dependent manner.

[0143] The above results indicate that the Chinese medicine composition of Example 1 of the present invention can improve the pathological condition of dysplasia by regulating the dysplasia markers of the gastric mucosa of PLGC model mice.

[0144] 10. Expression levels of gastric mucosal tumor markers HER2, TP53, and Ki67 in each group of mice

[0145] The mRNA expression levels of HER2, TP53, and Ki67 in the gastric mucosa of each group of mice were detected by RT-qPCR. The test results are shown in Tables 7 and Fig.11 As shown in Table 7 and Fig.11 The results of A show that compared with the model control group, the HER2 mRNA expression level in the blank control group was lower and there was a statistical difference. The HER2 mRNA expression levels in the other groups showed a downward trend, but there was no statistical difference. Fig.11 The results of B show that, for the mRNA expression level of TP53 in gastric mucosa, compared with the model control group, after drug intervention, the expression levels of the positive drug group and each dose group of Chinese medicine increased, and there was a statistical difference; as shown in Table 7 and Fig.11 The results of C show that, for the mRNA expression level of gastric mucosal Ki67, compared with the model control group, after drug intervention, the expression levels of the positive drug group and each dose group of Chinese medicine showed a downward trend, but except for the high-dose Chinese medicine group, there was no statistical difference among other groups.

[0146] Table 7 mRNA expression levels of HER2, TP53 and Ki67 in mouse gastric mucosa

[0147]

[0148] III. Effect of the Chinese medicine composition provided in Example 1 of the present invention on liver and kidney function of PLGC mouse model

[0149] Hitachi 7080 fully automatic biochemical analyzer was used to detect the expression levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE), and urea (Urea) in serum samples stored in a -80°C refrigerator to clarify the effect of the Chinese medicine composition provided in Example 1 on the liver and kidney function of the gastric precancerous lesion mouse model. The test results are shown in Tables 8 and Fig.12 shown.

[0150] Table 8 Serum AST, ALT, CRE, and Urea expression levels of mice in each group (M (P 25 ,M 75 ))

[0151]

[0152]

[0153] By the following table 8 and Fig.12 The results show that the expression levels of AST and ALT in the PLGC mice in the model control group were significantly higher than those in the blank control group (P<0.05), indicating that the MNU chemical carcinogenic inducer can affect the liver function of C57 mice and cause liver damage in mice. After 14 weeks of treatment with the positive control drug (folic acid tablets) and the low, medium and high doses of the Chinese medicine composition of Example 1 of the present invention, the AST and ALT levels of the PLGC mice decreased significantly. Compared with the model control group, the AST and ALT levels of the high-dose group (P<0.05) were statistically different, indicating that the Chinese medicine composition of Example 1 of the present invention had no damage to the liver function of the PLGC mice, and could reverse the liver damage caused by the MNU chemical carcinogenic inducer to a certain extent and prevent liver toxicity. At the same time, the CRE and Urea levels of PLGC mice in the model control group tended to be higher than those of normal mice in the blank control group, but the difference was not statistically significant (P≥0.05), indicating that the MNU chemical carcinogenic inducer can slightly affect the renal function of C57 mice; the CRE and Urea levels of PLGC mice were slightly reduced after intervention with various doses of Chinese medicine and the positive control drug, but there was no significant difference compared with the blank control group, indicating that the Chinese medicine composition of Example 1 of the present invention has no damage to the renal function of PLGC mice, and can improve the renal function effect caused by the MNU chemical carcinogenic inducer to a certain extent.

[0154] Although the embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the claims and their equivalents.

Claims

1. A Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions, characterized in that: The Chinese medicine composition is made of the following raw materials in parts by weight: 8-15 parts of ginseng, 15-45 parts of quinquefolius, 10-30 parts of Acanthopanax senticosus, 5-15 parts of Fructus Aurantii Immaturus, 10-30 parts of Rhizoma Tripterocarpis, 10-20 parts of Rhizoma Curcumae, 5-15 parts of Rhizoma Paris polyphyllae, 3-6 parts of Scorpio, 3-5 parts of Scolopendra subspinipes, 10-30 parts of Rhizoma Cynomorii and 5-15 parts of Radix Glycyrrhizae Preparata.

2. The Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions according to claim 1, characterized in that: The Chinese medicine composition is made of the following raw materials in parts by weight: 10 parts of ginseng, 30 parts of quinquefolius, 20 parts of Acanthopanax senticosus, 10 parts of Fructus Aurantii Immaturus, 15 parts of Rhizoma Tripterygii, 15 parts of Rhizoma Curcumae, 9 parts of Rhizoma Paris, 5 parts of Scorpio, 3 parts of Scolopendra, 20 parts of Rhizoma Lophatheri and 10 parts of Radix Glycyrrhizae Preparata.

3. A method for preparing a Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions according to claim 1 or 2, characterized in that: The following steps are involved: S1. Weigh 8-15 parts of ginseng, 15-45 parts of quinquefolius, 10-30 parts of Acanthopanax senticosus, 5-15 parts of Fructus Aurantii Immaturus, 10-30 parts of Rhizoma Tripterygii, 10-20 parts of Rhizoma Curcumae, 5-15 parts of Rhizoma Paris, 3-6 parts of Scorpio, 3-5 parts of Scolopendra, 10-30 parts of Rhizoma Cynomorii and 5-15 parts of Radix Glycyrrhizae Preparata respectively, and set aside; S2, mixing and crushing the ginseng, quinquefolius, Acanthopanax, Fructus Aurantii Immaturus, Rhizoma Curcumae, Rhizoma Paris, Rhizoma Cyperi and Radix Glycyrrhizae Preparata weighed in step S1 to obtain crushed drugs, and then sieving to obtain coarse drug powder; S3, soaking the crude drug powder obtained in step S2 in water for 1-2 hours, boiling over high heat, then decocting over low heat for 1-2 hours, filtering and separating to obtain a filter residue and a primary filtrate; S4, adding water to the filter residue obtained in step S3, boiling for 1-2 hours, filtering and separating to obtain a secondary filtrate, combining the secondary filtrate with the primary filtrate to obtain a water extract; S5, extracting the scorpion and centipede weighed in step S1 with ethanol to obtain an ethanol extract; S6. Mix the water extract and the alcohol extract, concentrate under reduced pressure at 60-65° C. to obtain concentrated medicine, and then freeze-dry in a vacuum to obtain freeze-dried powder, i.e., the Chinese medicine composition.

4. The method for preparing the Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions according to claim 3, characterized in that: In step S2, the particle size of the crushed medicine is 2 mm, and the mesh size of the sieved mesh is 10 meshes.

5. The method for preparing the Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions according to claim 3, characterized in that: In step S3, the volume ratio of the drug coarse powder to water is 1:10-12.

6. The method for preparing the Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions according to claim 3, characterized in that: In step S4, the volume ratio of the filter residue to water is 1:10-12.

7. The method for preparing the Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions according to claim 3, characterized in that: Step S5 specifically includes the following steps: Add ethanol to the scorpion and centipede weighed in step S1 for reflux extraction, perform reflux extraction three times in total, each time for 0.5 h, combine the three extracts, centrifuge, take the supernatant and condense it by suspension evaporation until the ethanol is completely volatilized, and obtain an alcohol extract.

8. The method for preparing the Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions according to claim 6, characterized in that: The weight ratio of the total weight of the scorpion and the centipede to the amount of ethanol added is 1:4-6.

9. The method for preparing the Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions according to claim 3, characterized in that: In step S6, the concentration of the concentrated drug is 1-2 g / L, the freezing temperature is -80°C or -20°C, the freezing time is 4-6 h or 12-24 h, the vacuum drying temperature is -60-70°C, and the vacuum drying time is 24-48 h.

10. Use of the Chinese medicine composition for treating chronic atrophic gastritis and gastric precancerous lesions according to claim 1 or 2 in preparing medicine for treating chronic atrophic gastritis and gastric precancerous lesions.

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