Traditional Chinese medicine composition for treating gastric precancerous state as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention provides a traditional Chinese medicine composition for treating a gastric precancerous state as well as a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 25-35 parts of fried malt, 25-35 parts of fried rice-grain sprout, 10-20 parts of endothelium corneum gigeriae galli, 15-25 parts of bran-fried bighead atractylodes rhizome, 6-15 parts of bran-fried immature bitter orange, 2-10 parts of agilawood, 10-20 parts of eclipta, 6-15 parts of dendrobe, 6-15 parts of curcuma zedoary, 10-20 parts of perilla stem and 2-10 parts of liquorice. The traditional Chinese medicine composition can obviously improve clinical symptoms such as gastral cavity fullness or dull pain, early satiety, putrid belching and acid swallowing, inappetence, fatigue and weakness, borborygmus and belching and the like after a patient eats food, reverses gastric mucosa atrophy and intestinal metaplasia, reduces the onset risk of gastric cancer, and has the effect of treating the pregastric state.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for treating gastric precancerous state, and a preparation method and application thereof. Background Art

[0002] Gastric precancerous state refers to the most common gastric mucosal state that progresses to gastric adenocarcinoma, including gastric mucosal atrophy and intestinal metaplasia, collectively referred to as chronic atrophic gastritis. The prevalence of gastric precancerous state in my country has gradually increased and tends to be younger. Taking South China as an example, the prevalence of gastric precancerous state increased from 18.78% between 2011 and 2015 to 22.30% between 2016 and 2020. Early detection, early diagnosis, and early treatment of gastric precancerous state, especially in patients with high risk of canceration, are important contents for achieving secondary prevention of gastric cancer in my country. Since modern medicine has not yet clarified the pathogenesis of gastric precancerous state and there are many inducing factors, chemical drugs such as folic acid often find it difficult to achieve satisfactory therapeutic effects, and most of them have no high-quality evidence to support their exact efficacy. In recent years, more and more attention has been paid to traditional drugs in the research and development of drugs for the treatment of gastric precancerous state at home and abroad, making traditional Chinese medicine occupy a very important position in the treatment of this disease.

[0003] Although there are prescriptions for different TCM syndromes of gastric precancerous conditions, some compound prescriptions have added anti-cancer and detoxifying Chinese medicines such as Hedyotis diffusa, Scutellaria barbata, Scorpio, and Gecko. Most of these Chinese medicines are bitter and cold, and they can easily damage the body's vital energy if they are too aggressive. Some insect medicines are also toxic, and there are risks in long-term use. In addition, the treatment cycle of gastric precancerous conditions is long, and detoxifying Chinese medicines often have a bad smell. Adding them to the prescription can easily make the taste worse, and patients are unwilling to take them, and it is difficult to persist, affecting the efficacy. Therefore, there is an urgent need for a Chinese medicine compound with a good taste, small toxic side effects, and high efficiency for gastric precancerous conditions to be applied in clinical practice. Summary of the invention

[0004] In view of the deficiencies in the prior art, the purpose of the present invention is to provide a

[0005] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0006] In the first aspect, the present invention provides a traditional Chinese medicine composition for treating gastric precancerous condition, comprising the following raw materials in parts by weight: 25-35 parts of fried malt, 25-35 parts of fried rice sprouts, 10-20 parts of chicken gizzard lining, 15-25 parts of fried Atractylodes macrocephala with bran, 6-15 parts of fried Citrus aurantium with bran, 2-10 parts of agarwood, 10-20 parts of Eclipta prostrata, 6-15 parts of Dendrobium officinale, 6-15 parts of Curcuma zedoaria, 10-20 parts of Perilla stem, and 2-10 parts of licorice.

[0007] Preferably, in the traditional Chinese medicine composition for treating gastric precancerous condition, the weight ratio of the fried malt, fried rice sprouts and chicken's gizzard lining is 2:2:1.

[0008] Preferably, in the traditional Chinese medicine composition for treating gastric precancerous condition, the weight ratio of the stir-fried Atractylodes macrocephala, stir-fried Citrus aurantium, and Aquilaria sinensis is 4:2:1.

[0009] Preferably, in the traditional Chinese medicine composition for treating gastric precancerous condition, the weight ratio of Eclipta prostrata, Dendrobium officinale, Curcuma zedoaria and Perilla stem is 1.5:1:1:1.5.

[0010] Preferably, the Chinese medicine composition for treating gastric precancerous condition further comprises pharmaceutically acceptable excipients, and the excipients include at least one of fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and bases.

[0011] Preferably, the filler comprises at least one of starch, pregelatinized starch, lactose, mannitol, chitosan, microcrystalline cellulose and sucrose.

[0012] Preferably, the disintegrant comprises at least one of starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, and cross-linked sodium carboxymethyl cellulose.

[0013] Preferably, the lubricant comprises at least one of magnesium stearate, sodium lauryl sulfate, talc and silicon dioxide.

[0014] Preferably, the suspending agent comprises at least one of polyvinyl pyrrolidone, microcrystalline cellulose, sucrose, agar, and hydroxypropyl methylcellulose.

[0015] Preferably, the adhesive comprises at least one of starch slurry, polyvinyl pyrrolidone and hydroxypropyl methylcellulose.

[0016] Preferably, the sweetener comprises at least one of aspartame, xylitol, mannitol, sorbitol and sucrose.

[0017] Preferably, the preservative comprises: at least one of sorbic acid, benzoic acid, sodium benzoate, and parabens.

[0018] Preferably, the matrix includes: at least one of an oil-soluble matrix, an emulsion matrix, a water-soluble matrix, and an external ointment.

[0019] In a second aspect, the present invention provides an oral dosage form for treating gastric precancerous condition, wherein the oral dosage form comprises the traditional Chinese medicine composition for treating gastric precancerous condition.

[0020] Preferably, the oral dosage form includes at least one of tablets, capsules, granules, pills, powders, and oral liquids.

[0021] The third aspect is the use of the traditional Chinese medicine composition in the preparation of medicines for treating precancerous conditions of the stomach.

[0022] In a fourth aspect, the present invention provides a method for preparing the Chinese medicine composition for treating gastric precancerous condition or preparing the oral dosage form medicine for treating gastric precancerous condition, comprising the following steps:

[0023] S1. crushing the raw materials of the traditional Chinese medicine composition for treating gastric precancerous condition respectively, and mixing them into a composition according to the required weight parts;

[0024] S2 extracting the composition of step S1 according to a conventional extraction method to obtain an extract;

[0025] S3: the extract of step S2 is subjected to a refining and purification process to obtain an effective fraction, and the extract and the effective fraction are mixed to obtain the Chinese medicine composition for treating gastric precancerous condition;

[0026] S4: further preparing the Chinese medicine composition of step S3 according to conventional preparation process to obtain a conventional oral dosage form.

[0027] Preferably, the conventional extraction method includes at least one of maceration extraction, decoction extraction, reflux extraction, percolation extraction, ultrasonic extraction and microwave extraction.

[0028] Preferably, the extraction solvent comprises water or a conventional organic solvent, such as ethanol, methanol, ethyl acetate, petroleum ether, isopropanol.

[0029] Preferably, the refining and purification process includes at least one of extraction, column chromatography separation, and high performance liquid chromatography separation.

[0030] Preferably, the oral dosage form includes at least one of tablets, capsules, granules, pills, powders, and oral liquids.

[0031] The beneficial effects of the present invention are as follows: the Chinese medicine composition for treating gastric precancerous state of the present invention is a pure Chinese medicine prescription, has good clinical efficacy, and combines disease differentiation and medication to prevent canceration on the basis of the effects of digestion, strengthening stomach, descending qi and regulating spleen in traditional Chinese medicine. Clinical studies have shown that the use of the Chinese medicine preparation of the present invention can significantly improve the clinical symptoms such as fullness or dull pain in the stomach after eating, early satiety, belching, loss of appetite, fatigue, intestinal borborygmus, etc., reverse gastric mucosal atrophy and intestinal metaplasia, and reduce the risk of gastric cancer. In addition, it has a wide source of medicine, low cost, and small toxic and side effects, which is of great significance to further improve the clinical efficacy of traditional Chinese medicine in treating gastric precancerous state and reduce the incidence of gastric cancer, and is suitable for clinical promotion and application.

[0032] The results of the experiment showed that the atrophy pathology score (P<0.05), the intestinal metaplasia pathology score (P<0.05), the operable gastritis staging scoring system (OL atrophy) score (P<0.05), the TCM syndrome score (P<0.01) and the endoscopic mucosal manifestation score (P<0.05) of the experimental group and the control group after treatment with the Chinese medicine composition of the present invention were significantly reduced compared with those before treatment. After treatment, the TCM syndrome score (P<0.01) and the endoscopic mucosal manifestation score (P<0.05) of the experimental group were significantly lower than those of the control group, and the difference before and after treatment was significantly higher than that of the control group. After treatment, the proportion of OL atrophy and operable intestinal metaplasia staging scoring system (OLG intestinal metaplasia) stages in the experimental group that were reduced to low-risk stages were higher than those in the control group, and the proportion of those that were upgraded to high-risk stages were lower than those in the control group.

[0033] Animal experiments verified the therapeutic effect of Xiaoshi Lipi Fang on the rat model of gastric precancerous state. After 8 weeks of administration, the gross morphology and pathological histology of the stomach of rats in the Xiaoshi Lipi Fang intervention group were improved, among which the improvement was most significant in the medium-dose group. In terms of gastric function, the serum PGⅠ, PGR, and G-17 levels of rats in the model group were significantly lower than those in the normal group (P<0.01), and those in the Xiaoshi Lipi Fang intervention group were significantly higher than those in the model group (P<0.01); the serum MTL level of rats in the model group was significantly lower than that in the normal group (P<0.01), and those in the Xiaoshi Lipi Fang intervention group were significantly higher than those in the model group (P<0.05); the serum PGⅡ level of rats in the model group was significantly higher than that in the normal group (P<0.01), and those in the medium-dose Xiaoshi Lipi Fang group were significantly lower than those in the model group (P<0.01). In terms of inflammation, the levels of serum IL-1β, IL-6, and TNF-α in the model group were significantly higher than those in the normal group (P<0.01), the levels of IL-1β in the low-dose and medium-dose groups of Xiaoshi Lipi Fang were significantly lower than those in the model group (P<0.05), and the levels of IL-6 and TNF-α in the Xiaoshi Lipi Fang intervention group were significantly lower than those in the model group (P<0.05). In terms of oxidative stress, the levels of serum SOD, GSH, and GSH-Px (P<0.01) in the model group were significantly lower, and the level of MDA was significantly higher (P<0.01). Compared with the model group, the levels of SOD, GSH-Px, and GSH in the medium-dose group of Xiaoshi Lipi Fang were significantly higher (P<0.05), and the level of MDA was significantly lower (P<0.05). BRIEF DESCRIPTION OF THE DRAWINGS

[0034] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation of the present invention. In the accompanying drawings:

[0035] Figure 1The stomach morphology of rats in each group is observed (Control is the normal group, Model is the model group, FA is the folic acid group, XSLP-L is the low-dose group of Xiaoshi Lipi Fang, XSLP-M is the medium-dose group of Xiaoshi Lipi Fang, and XSLP-H is the high-dose group of Xiaoshi Lipi Fang);

[0036] Figure 2 Schematic diagram of pathological changes in gastric mucosal tissues of rats in each group (Control is the normal group, Model is the model group, FA is the folic acid group, XSLP-L is the low-dose group of Xiaoshi Lipi Fang, XSLP-M is the medium-dose group of Xiaoshi Lipi Fang, and XSLP-H is the high-dose group of Xiaoshi Lipi Fang; AHE staining (×200), B AB-PAS staining (×100);

[0037] Figure 3 Schematic diagram of comparison of serum PGⅠ, PGⅡ, PGR, G-17 and MTL levels in rats of each group (Control is the normal group, Model is the model group, FA is the folic acid group, XSLP-L is the low-dose group of Xiaoshi Lipi Fang, XSLP-M is the medium-dose group of Xiaoshi Lipi Fang, and XSLP-H is the high-dose group of Xiaoshi Lipi Fang; compared with the normal group, ## indicates P < 0.01; compared with the model group, ** indicates P < 0.01, and * indicates P < 0.05);

[0038] Figure 4 Schematic diagram of comparison of serum IL-1β, IL-6 and TNF-α levels in rats of each group (Control is the normal group, Model is the model group, FA is the folic acid group, XSLP-L is the low-dose group of Xiaoshi Lipi Fang, XSLP-M is the medium-dose group of Xiaoshi Lipi Fang, and XSLP-H is the high-dose group of Xiaoshi Lipi Fang; compared with the normal group, ## indicates P < 0.01; compared with the model group, ** indicates P < 0.01, and * indicates P < 0.05);

[0039] Figure 5 Schematic diagram of the comparison results of serum SOD, GSH, GSH-Px and MDA levels in each group of rats (Control is the normal group, Model is the model group, FA is the folic acid group, XSLP-L is the low-dose group of Xiaoshi Lipi Fang, XSLP-M is the medium-dose group of Xiaoshi Lipi Fang, and XSLP-H is the high-dose group of Xiaoshi Lipi Fang; compared with the normal group, ## indicates P < 0.01, # indicates P < 0.05; compared with the model group, ** indicates P < 0.01, * indicates P < 0.05). DETAILED DESCRIPTION

[0040] The scheme of the present invention will be explained below in conjunction with the embodiments. It will be appreciated by those skilled in the art that the following embodiments are only used to illustrate the present invention and should not be considered as limiting the scope of the present invention. Where specific techniques or conditions are not indicated in the embodiments, the techniques or conditions described in the literature in this area or the product specifications are used. The reagents or instruments used are not indicated by the manufacturer and are all conventional products that can be obtained commercially.

[0041] This embodiment provides a traditional Chinese medicine composition for treating gastric precancerous conditions, the composition comprises the following traditional Chinese medicine raw materials in parts by weight:

[0042] 25-35 parts of roasted malt, further, the weight parts of the roasted malt in the present invention can be any value of 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or 35 or the range value therebetween.

[0043] 25-35 parts of fried rice sprouts, further the weight parts of the fried rice sprouts in the present invention can be 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or 35 any value or the range value therebetween.

[0044] 10-20 parts of chicken's gizzard lining, further the weight parts of the chicken's gizzard lining in the present invention can be 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 2 any number or the range value 0 therebetween.

[0045] 15-25 parts of bran-fried Atractylodes macrocephala, further, the weight parts of the bran-fried Atractylodes macrocephala in the present invention can be 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 any number or a range therebetween.

[0046] 6-15 parts of stir-fried Citrus aurantium with bran, and further the weight parts of the stir-fried Citrus aurantium with bran in the present invention can be any value of 6, 7, 8, 9, 10, 11, 12, 13, 14 or 1 or a range value of 5 therebetween.

[0047] 2-10 parts of agarwood. Further, the weight of the agarwood in the present invention can be any number of 2, 3, 4, 5, 6, 7, 8, 9 or 10 or a range therebetween.

[0048] 10-20 parts of Eclipta prostrata, further, the weight parts of Eclipta prostrata in the present invention can be any value of 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 or the range therebetween.

[0049] 6-15 parts of Dendrobium, further, the weight parts of Dendrobium in the present invention can be 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 or any value or a range therebetween.

[0050] 6-15 parts of Curcuma zedoaria, further, the weight parts of Curcuma zedoaria in the present invention can be 6, 7, 8, 9, 10, 11, 12, 13, 14 or 1 or any value in the range of 5 therebetween.

[0051] 10-20 parts of perilla stems, further, the weight parts of the perilla stems in the present invention can be 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 or any value or a range therebetween.

[0052] 2-10 parts of licorice, further, the weight parts of licorice in the present invention can be any value of 2, 3, 4, 5, 6, 7, 8, 9 or 10 or a range therebetween.

[0053] The prescription and treatment method and compatibility characteristics of the present invention are as follows:

[0054] The prescription of the Chinese medicine composition of the present invention is named as the prescription for digestion and spleen regulation, and the main treatment methods are digestion and stomach strengthening, descending qi and regulating spleen. The prescription follows the principle of "monarch, minister, assistant and messenger" of Chinese medicine prescription, and stir-fried rice sprouts, stir-fried malt and chicken gizzard lining are used as monarch drugs to digestion, stomach strengthening and digestion; stir-fried agarwood, stir-fried bitter orange and stir-fried white atractylodes are used as minister drugs, and stir-fried agarwood and stir-fried bitter orange are used as key drugs for qi, and play the role of promoting qi and relieving bloating, descending qi and descending adverse qi, and stir-fried white atractylodes is used to regulate spleen qi and help descend stomach qi; Eclipta prostrata, Dendrobium officinale, Curcuma zedoaria and Perilla stem are used as adjuvant drugs, among which Eclipta prostrata is used to restrain liver yin, Dendrobium officinale is used to clear stomach heat and nourish stomach yin, Curcuma zedoaria is used to remove blood stasis and detoxify, relieve pain and soothe the stomach, and can also stimulate appetite, digestion and relieve the stagnation of tonic drugs, and Perilla stem is used to smooth qi and harmonize the stomach, and can also raise the spleen qi; Licorice is used as a messenger drug to harmonize various drugs.

[0055] Fried malt and rice sprouts can eliminate the food accumulation of staple food such as rice, flour, potato and taro. Modern people eat more refined rice and flour. Malt and rice sprouts contain rich enzymes to help digestion. At the same time, the various vitamins and amino acids they contain can also supplement the trace elements lacking in refined rice and flour.

[0056] Chicken's gizzard lining is rich in nutritional value, high in protein, and contains pepsin to help gastrointestinal digestion. In patients with precancerous gastric cancer and intestinal metaplasia, mucosal granules or nodules can be seen under endoscopy, which falls into the category of "accumulation". Therefore, using chicken's gizzard lining can also improve intestinal metaplasia.

[0057] The combination of agarwood, stir-fried immature bitter orange and stir-fried white atractylodes can invigorate the spleen qi on the basis of lowering stomach qi, treat the spleen and stomach together, and regulate both rising and falling.

[0058] Mechanism of action of Eclipta prostrata, Dendrobium officinale, Curcuma zedoaria, and Perilla stem: Eclipta prostrata has multiple pharmacological activities such as lowering blood lipids, anti-oxidation, anti-inflammatory, and immunomodulatory; Dendrobium officinale can clear stomach heat and nourish stomach yin, Curcuma zedoaria can remove blood stasis and detoxify, relieve pain and soothe the stomach, and Perilla stem can smooth the qi and harmonize the stomach, and can also clear the spleen.

[0059] Licorice's mechanism of action: Licorice is used to harmonize various medicines.

[0060] It should be noted that, according to the compatibility characteristics of the raw materials of the above-mentioned composition, the weight portions of the above-mentioned raw materials can be arbitrarily selected within a limited range, as long as the compatibility formula of using fried rice sprouts, fried malt, and chicken's gizzard lining as the main medicine, using agarwood, fried immature bitter orange, and fried white atractylodes as the ministerial medicine, using Eclipta prostrata, Dendrobium officinale, Curcuma zedoaria, and Perilla stem as adjuvants, and using licorice as the guiding medicine, can achieve the purpose of the present invention.

[0061] According to the roles and effects of the above-mentioned various raw materials in the present invention, the Chinese medicine composition of the present invention can also be composed of the following pharmaceutical composition formula:

[0062] Further preferably, the Chinese medicine composition includes the following raw materials in parts by weight: 28-32 parts of roasted malt, 28-32 parts of roasted rice sprouts, 14-16 parts of chicken's gizzard lining, 18-22 parts of roasted Atractylodes macrocephala with bran, 8-12 parts of roasted Citrus aurantium with bran, 4-6 parts of agarwood, 14-16 parts of Eclipta prostrata, 8-12 parts of Dendrobium officinale, 8-12 parts of Curcuma zedoaria, 14-16 parts of Perilla stem, and 4-6 parts of licorice.

[0063] Further preferably, the Chinese medicine composition is composed of the following raw materials in parts by weight: 25 parts of fried malt, 25 parts of fried rice sprouts, 12.5 parts of chicken gizzard lining, 25 parts of fried Atractylodes macrocephala with bran, 12.5 parts of fried Citrus aurantium with bran, 6.25 parts of agarwood, 20 parts of Eclipta prostrata, 13 parts of Dendrobium officinale, 13 parts of Curcuma zedoaria, 20 parts of Perilla stems, and 2 parts of licorice.

[0064] Through a large number of experimental studies, the invention finds that when the weight ratio of fried malt, fried rice sprouts and chicken gizzard lining in the main medicine is 2:2:1, the weight ratio of fried white atractylodes macrocephala, fried immature bitter orange and agarwood in the auxiliary medicine is 4:2:1, and the weight ratio of Eclipta prostrata, Dendrobium officinale, Curcuma zedoaria and Perilla stem in the adjuvant medicine is 1.5:1:1:1.5, the therapeutic effect of the prescription for digestion and regulating the spleen of the invention is best.

[0065] Another embodiment of the present invention provides a method for preparing the Chinese medicine composition of the present invention, and the specific method is as follows:

[0066] A composition obtained by pulverizing the raw materials of the traditional Chinese medicine composition for treating precancerous conditions of the stomach separately and then mixing them; or, the raw materials are mixed and extracted according to a conventional extraction method to obtain an extract, the extract is further subjected to a refining and purification process to obtain an effective fraction, and the extract and effective fraction are further prepared according to a conventional preparation process to obtain a conventional oral dosage form.

[0067] The above-mentioned conventional extraction methods include immersion extraction, decoction extraction, reflux extraction, percolation extraction, ultrasonic extraction, microwave extraction, etc.; the extraction solvent includes water or conventional organic solvents, such as ethanol, methanol, ethyl acetate, petroleum ether, isopropanol, etc.; the refining and purification process includes extraction, column chromatography separation, high performance liquid chromatography separation, etc.

[0068] The above conventional oral dosage forms include tablets, capsules, granules, pills, powders, and oral liquids. The preparation of the above dosage forms requires the addition of commonly used pharmaceutically acceptable excipients, including fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, bases, etc. Fillers include starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, etc.; disintegrants include starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, etc.; lubricants include magnesium stearate, sodium lauryl sulfate, talc, silicon dioxide, etc.; suspending agents include polyvinyl pyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, etc.; binders include starch slurry, polyvinyl pyrrolidone, hydroxypropyl methylcellulose, etc.

[0069] During use, the Chinese medicine composition of the present application can be fed in the form of raw materials, as well as in the form of extracts of a certain proportion or in the form of granules. The extract can be a water extract of each raw material, or an organic solvent extract, or a refined product obtained by further refining and purification of the water extract / organic solvent extract, or further made into a formula granule. The organic solvent is selected from one or more of methanol, 20-95% ethanol solution, and acetone; the extraction method used to prepare the above extract includes any one of reflux extraction, immersion extraction, ultrasonic extraction or percolation extraction, or a combination of different extraction methods.

[0070] Example 1

[0071] A Chinese medicine composition for treating gastric precancerous condition is composed of the following raw materials in parts by weight:

[0072] 35 parts of stir-fried malt, 25 parts of stir-fried rice sprouts, 10 parts of chicken's gizzard lining, 15 parts of stir-fried atractylodes macrocephala with bran, 6 parts of stir-fried immature bitter orange with bran, 2 parts of agarwood, 10 parts of Eclipta prostrata, 15 parts of dendrobiums, 6 parts of zedoaria, 10 parts of perilla stems, and 2 parts of liquorice.

[0073] Preparation method: Soak all the herbs in clean water for 30 minutes. The best amount of water should be enough to cover the herbs by three to five centimeters. Boil over high heat first, then simmer over low heat. Boil the remaining herbs except agarwood for 40 minutes. Add agarwood 10 minutes before the end of the first decoction and boil for 30 minutes for the second decoction. Filter out the two medicinal liquids, mix them together, shake well, and take warm twice a day, morning and evening.

[0074] Functions and indications: helps digestion and strengthens the stomach, descends qi and regulates the spleen. It is used for abdominal distension or dull pain after eating, early satiety, belching, loss of appetite, fatigue, borborygmus, pale tongue, greasy white fur, and slippery or deep pulse caused by long-term irregular diet or partiality; patients with the above symptoms in the precancerous state of stomach cancer.

[0075] Example 2

[0076] A Chinese medicine composition for treating gastric precancerous condition is composed of the following raw materials in parts by weight:

[0077] 25 parts of stir-fried malt, 35 parts of stir-fried rice sprouts, 20 parts of chicken's gizzard lining, 25 parts of stir-fried atractylodes macrocephala with bran, 15 parts of stir-fried immature bitter orange with bran, 10 parts of agarwood, 20 parts of Eclipta prostrata, 6 parts of dendrobiums, 15 parts of zedoaria, 20 parts of perilla stems, and 10 parts of liquorice.

[0078] The preparation method and functions are the same as those in Example 1.

[0079] Example 3

[0080] A Chinese medicine composition for treating gastric precancerous condition is composed of the following raw materials in parts by weight:

[0081] 30 parts of stir-fried malt, 30 parts of stir-fried rice sprouts, 15 parts of chicken's gizzard lining, 15 parts of stir-fried atractylodes macrocephala with bran, 7.5 parts of stir-fried immature bitter orange with bran, 3.7 parts of agarwood, 15 parts of Eclipta prostrata, 10 parts of dendrobiums, 10 parts of zedoaria, 15 parts of perilla stems, and 5 parts of liquorice.

[0082] The preparation method and functions are the same as those in Example 1.

[0083] Example 4

[0084] A Chinese medicine composition for treating gastric precancerous condition is composed of the following raw materials in parts by weight:

[0085] 25 parts of stir-fried malt, 25 parts of stir-fried rice sprouts, 12.5 parts of chicken's gizzard lining, 25 parts of stir-fried atractylodes macrocephala with bran, 12.5 parts of stir-fried immature bitter orange with bran, 6.25 parts of agarwood, 20 parts of Eclipta prostrata, 13 parts of dendrobiums, 13 parts of zedoariae, 20 parts of perilla stems, and 2 parts of liquorice.

[0086] The preparation method and functions are the same as those in Example 1.

[0087] Comparative Example 1

[0088] The difference between Comparative Example 1 and Example 4 is that there is no fried malt, and the composition of Comparative Example 1 is specifically as follows: 50 parts of fried rice sprouts, 12.5 parts of chicken gizzard lining, 25 parts of bran-fried Atractylodes macrocephala, 12.5 parts of bran-fried Citrus aurantium, 6.25 parts of Aquilaria sinensis, 20 parts of Eclipta prostrata, 13 parts of Dendrobium officinale, 13 parts of Curcuma zedoariae, 20 parts of Perilla stems, and 2 parts of Licorice. The preparation method is the same as that of Example 4.

[0089] Comparative Example 2

[0090] The difference between Comparative Example 2 and Example 4 is that there is a lack of chicken gizzard lining, and the composition of Comparative Example 3 is specifically: 28 parts of fried malt, 28 parts of fried rice sprouts, 25 parts of bran-fried Atractylodes macrocephala, 12.5 parts of bran-fried Citrus aurantium, 6.25 parts of Aquilaria, 20 parts of Eclipta prostrata, 13 parts of Dendrobium, 13 parts of Curcuma, 20 parts of Perilla stems, and 2 parts of Licorice. The preparation method is the same as that of Example 4.

[0091] Comparative Example 3

[0092] The difference between Comparative Example 3 and Example 4 is that bran-fried Citrus aurantium is lacking, and the composition of Comparative Example 3 is specifically as follows: 25 parts of fried malt, 25 parts of fried rice sprouts, 12.5 parts of chicken gizzard lining, 31 parts of bran-fried Atractylodes macrocephala, 12 parts of Aquilaria sinensis, 20 parts of Eclipta prostrata, 13 parts of Dendrobium officinale, 13 parts of Curcuma zedoariae, 20 parts of Perilla stems, and 2 parts of Licorice. The preparation method is the same as that of Example 4.

[0093] Comparative Example 4

[0094] The difference between Comparative Example 4 and Example 4 is that there is no agarwood, and the composition of Comparative Example 4 is specifically: 25 parts of fried malt, 25 parts of fried rice sprouts, 12.5 parts of chicken gizzard lining, 28 parts of bran-fried Atractylodes macrocephala, 15 parts of bran-fried Citrus aurantium, 20 parts of Eclipta prostrata, 13 parts of Dendrobium, 13 parts of Curcuma, 20 parts of Perilla stems, and 2 parts of Licorice. The preparation method is the same as that of Example 4.

[0095] Comparative Example 5

[0096] The difference between Comparative Example 5 and Example 4 is that there is no Eclipta prostrata, and the composition of Comparative Example 5 is specifically: 25 parts of fried malt, 25 parts of fried rice sprouts, 12.5 parts of chicken gizzard lining, 25 parts of bran-fried Atractylodes macrocephala, 12.5 parts of bran-fried Citrus aurantium, 6.25 parts of Aquilaria sinensis, 19 parts of Dendrobium officinale, 19 parts of Curcuma zedoariae, 26 parts of Perilla stems, and 2 parts of Licorice. The preparation method is the same as that of Example 4.

[0097] Comparative Example 6

[0098] The difference between Comparative Example 6 and Example 4 is that there is no Curcuma zedoaria, and the composition of Comparative Example 6 is specifically: 25 parts of fried malt, 25 parts of fried rice sprouts, 12.5 parts of chicken gizzard lining, 25 parts of bran-fried Atractylodes macrocephala, 12.5 parts of bran-fried Citrus aurantium, 6.25 parts of Aquilaria sinensis, 24 parts of Eclipta prostrata, 17 parts of Dendrobium officinale, 24 parts of Perilla stems, and 2 parts of Licorice. The preparation method is the same as that of Example 4.

[0099] Comparative Example 7

[0100] The difference between Comparative Example 7 and Example 4 is that there is no licorice, and the composition of Comparative Example 7 is specifically: 25 parts of fried malt, 25 parts of fried rice sprouts, 12.5 parts of chicken gizzard, 25 parts of bran-fried Atractylodes macrocephala, 12.5 parts of bran-fried Citrus aurantium, 6.25 parts of Aquilaria sinensis, 20 parts of Eclipta prostrata, 13 parts of Dendrobium officinale, 13 parts of Curcuma zedoariae, and 20 parts of Perilla stem. The preparation method is the same as that of Example 4.

[0101] Comparative Example 8

[0102] The difference between Comparative Example 8 and Example 4 is that the monarch drug and the minister drug are reversed, and the composition of Comparative Example 8 is specifically as follows: 25 parts of bran-fried Atractylodes macrocephala, 25 parts of bran-fried Citrus aurantium, 12.5 parts of agarwood, 25 parts of fried malt, 12.5 parts of fried rice sprouts, 6.25 parts of chicken gizzard lining, 20 parts of Eclipta prostrata, 13 parts of Dendrobium officinale, 13 parts of Curcuma zedoariae, 20 parts of Perilla stem, and 2 parts of Licorice. The preparation method is the same as that of Example 4.

[0103] Comparative Example 9

[0104] The difference between Comparative Example 9 and Example 4 is that the adjuvant and the ministerial drug are reversed, and the composition of Comparative Example 9 is specifically as follows: 25 parts of fried malt, 25 parts of fried rice sprouts, 12.5 parts of chicken gizzard lining, 25 parts of Eclipta prostrata, 12.5 parts of Dendrobium officinale, 3.12 parts of Curcuma zedoariae, 3.12 parts of Perilla stem, 40 parts of bran-fried Atractylodes macrocephalae, 13 parts of bran-fried Citrus aurantium, 13 parts of Aquilaria sinensis, and 2 parts of Licorice. The preparation method is the same as that of Example 4.

[0105] Comparative Example 10

[0106] The difference between Comparative Example 10 and Example 4 is that the main drug and the adjuvant are reversed, and the composition of Comparative Example 10 is specifically: 25 parts of Eclipta prostrata, 12.5 parts of Dendrobium officinale, 12.5 parts of Curcuma zedoariae, 12.5 parts of Perilla stems, 25 parts of bran-fried Atractylodes macrocephala, 12.5 parts of bran-fried Citrus aurantium, 6.25 parts of Aquilaria sinensis, 40 parts of fried malt, 13 parts of fried rice sprouts, 13 parts of chicken gizzard lining, and 2 parts of liquorice. The preparation method is the same as that of Example 4.

[0107] Comparative Example 11

[0108] The difference between Comparative Example 11 and Example 4 is that Licorice is replaced by Fritillaria cirrhosae, and the rest is the same as that of Example 4. The preparation method is the same as that of Example 4.

[0109] Comparative Example 12

[0110] The difference between Comparative Example 12 and Example 4 is that Licorice is replaced with Saposhnikovia divaricata, and the rest is the same as that of Example 4. The preparation method is the same as that of Example 4.

[0111] Comparative Example 13

[0112] The difference between Comparative Example 13 and Example 4 is that the weight ratio of the roasted malt, the roasted rice sprouts and the chicken's gizzard lining is 1:2:3, and the rest is the same as that of the Example. The preparation method is the same as that of Example 4.

[0113] Comparative Example 14

[0114] The difference between Comparative Example 14 and Example 4 is that there are 6.25 parts of bran-fried Atractylodes macrocephala, 12.5 parts of bran-fried Citrus aurantium, and 25 parts of Aquilaria sinensis, and the weight ratio of bran-fried Atractylodes macrocephala, bran-fried Citrus aurantium and Aquilaria sinensis is 1:2:4, and the rest is the same as the example. The preparation method is the same as that of Example 4.

[0115] Comparative Example 15

[0116] The difference between Comparative Example 15 and Example 4 is that 13 parts of Eclipta prostrata, 20 parts of Dendrobium officinale, 20 parts of Curcuma zedoaria, and 13 parts of Perilla stem are used, and the weight ratio of Eclipta prostrata, Dendrobium officinale, Curcuma zedoaria and Perilla stem is 1:1.5:1.5:1, and the rest is the same as the example. The preparation method is the same as that of Example 4.

[0117] Experimental Example 1

[0118] Observation on the therapeutic effect of the compound Chinese medicine composition of the present invention on the precancerous state of stomach cancer caused by spleen and stomach weakness and food accumulation and qi stagnation:

[0119] 1Case Source

[0120] Patients with gastric precancerous conditions who were admitted to the outpatient or inpatient department of the Department of Gastroenterology, Guangzhou University of Chinese Medicine Dongguan Hospital from June 2022 to September 2023 were included, and the cases were collected and enrolled in strict accordance with the inclusion and exclusion criteria. This study has been approved by the Medical Ethics Committee of Guangzhou University of Chinese Medicine Dongguan Hospital, and all subjects were informed of this study and signed the informed consent.

[0121] 2 Diagnostic criteria

[0122] Western medicine diagnostic standards: Refer to the "Expert Consensus on Treatment Strategies for Gastric Mucosal Precancerous Conditions and Precancerous Lesions in China (2020)". Gastric precancerous conditions include gastric mucosal atrophy and intestinal metaplasia. Gastric mucosal atrophy refers to the reduction of intrinsic glands in the gastric cavity, thinning of the gastric mucosa, and shallowing of the gastric pits; intestinal metaplasia refers to the replacement of gastric intrinsic glands by intestinal metaplastic glands or pseudopyloric metaplastic glands.

[0123] TCM diagnostic criteria: refer to the "TCM Clinical Diagnosis and Treatment Terminology Part 2: Syndromes" and "Expert Consensus on TCM Diagnosis and Treatment of Chronic Atrophic Gastritis in Lingnan Region (2022)" formulated by the National Technical Committee for Standardization of TCM, and the syndrome is spleen and stomach weakness with food accumulation and qi stagnation. Main symptoms: (1) fullness or dull pain in the stomach after eating; (2) early satiety. Secondary symptoms: (1) belching and acid regurgitation; (2) loss of appetite; (3) fatigue; (4) intestinal rumbling and flatulence. Tongue and pulse: pale tongue with greasy white fur; deep and slippery or deep and stringy pulse. If the main symptoms and two secondary symptoms are present, the diagnosis can be made by referring to the tongue and pulse.

[0124] 3 Inclusion criteria

[0125] (1) Those who meet the above-mentioned Western medical diagnostic criteria, have undergone gastroscopy within the past month, and whose pathological biopsy report indicates atrophy with intestinal metaplasia; (2) Those whose TCM syndrome differentiation is consistent with spleen and stomach weakness and food accumulation and qi stagnation; (3) Those aged 20 to 70 years old; (4) Those with a history of bad eating habits or dietary preferences; (5) Those who are negative for Helicobacter pylori as confirmed by urea breath test and gastroscopy pathological biopsy report, or whose positive eradication treatment has turned negative after one month of reexamination; (6) Those who have signed the informed consent form and voluntarily participated in this clinical trial.

[0126] 4 Exclusion criteria

[0127] (1) Patients with autoimmune gastritis; (2) Patients with intraepithelial neoplasia or gastric cancer as indicated by endoscopic biopsy reports; (3) Patients with organic lesions such as peptic ulcers, peptic ulcer polyps, digestive system tumors, peptic ulcer or abdominal surgery; (4) Patients with a history of gastric surgery; (5) Patients who have taken proton pump inhibitors, H2 receptor blockers, nonsteroidal drugs, gastric mucosal protective agents, traditional Chinese medicine, etc. in the past month; (6) Patients with primary diseases such as cardiovascular, cerebrovascular, liver, kidney, and hematopoietic system diseases; (7) Patients with mental illness and intellectual or language disorders; (8) Pregnant, pregnant or lactating women; (9) Patients with a history of allergy to the study drugs; (10) Patients who are participating in other clinical trials.

[0128] 5. Suspension, shedding and rejection criteria

[0129] (1) Serious or life-threatening adverse events; (2) The subject is unable to comply with the protocol requirements and complete the treatment; (3) The trial must be terminated based on the investigator's judgment and the subject's health; (4) The subject's request (the subject requests to terminate the treatment at any time for any reason); (5) The subject becomes pregnant or dies during the study.

[0130] 6 Treatments

[0131] 6.1 Treatment in the experimental group

[0132] The Chinese medicine compositions of Examples 1 to 4 and Comparative Examples 1 to 15 were used, and the course of treatment was 12 weeks.

[0133] 6.2 Treatment of the control group

[0134] According to the Expert Consensus on the Management Strategies of Gastric Mucosal Precancerous Conditions and Precancerous Lesions in China (2020), patients in the control group took folic acid tablets (Changzhou Pharmaceutical Factory Co., Ltd., batch number: National Medicine Standard H32023302) orally, 5 mg each time, 3 times a day, after meals. The course of treatment was 12 weeks.

[0135] 7. Evaluation indicators

[0136] 7.1 Primary outcome measures

[0137] The pathological scores of atrophy and intestinal metaplasia before and after treatment were compared between the two groups of patients. Referring to the pathological diagnosis and histological grading standards of atrophy and intestinal metaplasia in the "Guidelines for the Diagnosis and Treatment of Chronic Gastritis in China (2022, Shanghai)", the severity of atrophy and intestinal metaplasia was divided into four levels: none, mild, moderate, and severe, and scored 0, 1, 2, and 3 points respectively. The points were assigned according to the more severe level of lesions in the biopsy specimens. The differences before and after treatment of each group (30 people in each group) were compared. The larger the difference, the better the treatment effect. The difference = the average score of each group before treatment - the average score of each group after treatment. The results are shown in Table 1:

[0138] Table 1: Comparison of scores among groups

[0139]

[0140]

[0141] As shown in Table 1, the therapeutic effect of the embodiment group is better than that of the comparative example group, and the therapeutic effect of embodiment 4 is the best. This is because the ratio of each component in the monarch, minister, and adjuvant medicine is optimized in embodiment 4. It is found that when the weight ratio of fried malt, fried rice sprouts, and chicken gizzard lining in the monarch medicine is 2:2:1, the weight ratio of fried white atractylodes macrocephala, fried immature bitter orange, and agarwood in the minister medicine is 4:2:1, and the weight ratio of Eclipta prostrata, Dendrobium officinale, Curcuma zedoaria, and Perilla stem in the adjuvant medicine is 1.5:1:1:1.5, the therapeutic effect of the Xiaoshi Lipi prescription of the present invention is the best. It is found through comparative examples 1-7 that each component in the Xiaoshi Lipi prescription of the present invention also has a synergistic effect, and the therapeutic effect of the components of the present invention cannot be achieved due to the lack of one of the components in comparative examples 1-7. As can be seen from Comparative Examples 8-10, the specific compatibility of the prescription of the present invention has a specific therapeutic effect. In Comparative Examples 8-10, the meaning of the Chinese medicine prescription of "monarch, minister, assistant and messenger" of the present invention is changed, and the compatibility of monarch medicine, minister medicine and assistant medicine is adjusted. As a result, the therapeutic effects of Comparative Examples 8-10 are not as good as those of the embodiment group. As can be seen from Comparative Examples 11-12, the selection of the assistant medicine has a greater impact on the therapeutic effect of the Xiaoshi Lipi Fang of the present invention. Comparative Examples 11-12 respectively select other Chinese medicines, such as Fritillaria cirrhosa and Saposhnikovia divaricata, which also do not reach the therapeutic effect of the embodiment. It can be seen that the selection of licorice as the assistant medicine of the present invention can improve the therapeutic effect of the Xiaoshi Lipi Fang of the present invention. As can be seen from Comparative Examples 13-15, the ratio of each component in the monarch, minister and assistant medicine is also crucial. Therefore, the present invention optimizes the ratio of each component to achieve the best therapeutic effect.

[0142] 7.2 Secondary Outcome Measures

[0143] (1) OL atrophy and OLG intestinal metaplasia staging and scoring

[0144] As can be seen from Table 1, Example 4 (i.e., the experimental group) is the best solution of the present invention. Therefore, Example 4 was selected for subsequent experiments: the OL atrophy and OLG intestinal metaplasia stages and scores of the two groups of patients before and after treatment were compared. Referring to the staging method of the "Expert Guidance on the Diagnosis and Treatment of Chronic Atrophic Gastritis and the Clinical Application of Vitamin B12 from Lamb Stomach Extract", stages 0, I, and II were defined as low-risk stages, stages III and IV were defined as high-risk stages, and stages 0 to IV were divided into 0, 1, 2, 3, and 4 points, respectively. According to the gastric antrum (or gastric angle) and gastric body, the biopsy specimens with more severe lesions were selected for staging and scoring, and the average score of each group was the score of each group. The results are shown in Tables 2 to 5. The larger the difference, the better the treatment effect.

[0145] Table 2 Comparison of OL atrophy scores between the two groups of patients before and after treatment (P25, P50, P75)]

[0146]

[0147] Table 3 Comparison of OL atrophy stage changes between the two groups of patients after treatment (f, R)

[0148]

[0149] Table 4 Comparison of OLG intestinal metaplasia scores between the two groups of patients before and after treatment (P25, P50, P75)]

[0150]

[0151] Table 5 Comparison of changes in OLG intestinal metaplasia stages between the two groups of patients after treatment

[0152]

[0153] (2) TCM syndrome score

[0154] The TCM syndrome scores of the two groups of patients were compared before and after treatment. According to the Expert Consensus on TCM Diagnosis and Treatment of Chronic Atrophic Gastritis in Lingnan Region (2022) and the Expert Consensus on Quantitative Standards for Spleen and Stomach Disease Symptoms (2017), the main symptoms include fullness or dull pain in the stomach after eating, and early satiety. The secondary symptoms include belching, loss of appetite, fatigue, intestinal borborygmus, and belching. The tongue and pulse include white and greasy tongue coating, and a deep and slippery or deep and stringy pulse. Each symptom is divided into four levels according to frequency and degree: none, mild, moderate, and severe. The main symptoms are scored as 0, 2, 4, and 6, respectively, and the secondary symptoms are scored as 0, 1, 2, and 3, respectively. The tongue and pulse are scored as 0 and 1 according to the presence or absence, and the sum of the average scores is the TCM syndrome score of this disease. The results are shown in Table 6. The larger the difference, the better the treatment effect.

[0155] Table 6 Comparison of TCM syndrome scores between the two groups of patients before and after treatment (P25, P50, P75)]

[0156]

[0157] (3) Endoscopic mucosal manifestation score

[0158] The scores of gastroscopic mucosal manifestations before and after treatment were compared between the two groups of patients. According to the "Trial Opinions on Endoscopic Classification and Treatment of Chronic Gastritis", the main pathological manifestations of gastric mucosa observed under gastroscopy include mucosal color, texture, vascular transparency, intestinal metaplasia nodules and erosions. Each manifestation is divided into 0, I, II, and III grades according to the severity, and is scored as 0, 1, 2, and 3 respectively. The average score of each group is the score of each group. The results are shown in Table 7. The larger the difference, the better the treatment effect.

[0159] Table 7 Comparison of gastroscopy mucosal manifestation scores between the two groups of patients before and after treatment (P25, P50, P75)]

[0160]

[0161] 8 Safety evaluation

[0162] There were no significant abnormalities in the vital signs, three routine tests, liver function, kidney function, electrocardiogram and other safety indicators of the two groups of patients before and after treatment, and no adverse reactions were observed in the patients in the experimental group.

[0163] Experimental Example 2

[0164] Pharmacodynamic study of the compound Chinese medicine composition of the present invention (Example 4) in treating rats with gastric precancerous state

[0165] 1 Materials and methods

[0166] 72 SPF SD rats were randomly divided into a normal group (Control), a model group (Model), a folic acid group (FA), a low-dose (XSLP-L), a medium-dose (XSLP-M), and a high-dose (XSLP-H) group, with 12 rats in each group. The rats in the normal group were given normal drinking water and normal diet, and 10 mL / kg of normal saline was gavaged. The rats in the other groups were freely drinking 180 μg / mL of N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG) solution + freely eating feed containing 0.03% ranitidine + hunger and satiety disorder method to establish the model for 16 weeks, and the drug was administered from the 9th week for 8 consecutive weeks. In the folic acid group, each rat was gavaged with a folic acid solution at a dose of 3 mg / kg starting from the 9th week of modeling, and the drug was administered for 8 consecutive weeks. The Xiaoshi Lipi prescription adopts the Chinese medicine composition ratio of Example 1, and the high, medium and low dose groups are respectively concentrated into a concentration of 1g crude drug / mL, 0.5g crude drug / mL, and 0.25g crude drug / mL for gavage, and the drug is continuously administered for 8 weeks. The stomach morphology of rats was observed with the naked eye, and the pathological histological changes of gastric mucosa of rats were observed by hematoxylin-eosin (HE) and alycian blue-periodic acid Schiff (AB-PAS) staining. The thickness ratio of gastric mucosa layer to mucosal muscular layer of rats in each group was measured and calculated, and the levels of gastrointestinal hormones such as serum PGⅠ, PGⅡ, G-17, MTL and serum inflammatory factors such as IL-1β, IL-6, TNF-α in rats were detected by enzyme-linked immunosorbent assay (ELISA), and the oxidative stress-related indicators such as serum SOD, GSH, GSH-Px, MDA in rats were detected by microplate method.

[0167] 2 Index evaluation

[0168] 2.1 Observation of stomach morphology of rats in each group

[0169] The stomach morphology of rats in each group was observed with the naked eye. The gastric mucosa of rats in the normal group was orange-red in color, with a smooth surface and no edema or congestion. The gastric mucosa of rats in the model group was grayish in color, thinned, with fewer folds, and a rough texture. Nodular protrusions and submucosal vascular branches were partially visible on the mucosal surface. Significant congestion, edema, and erosion foci were observed in the gastric mucosa of some rats. Compared with the model group, the gastric mucosa of rats in the folic acid group and the low-, medium-, and high-dose groups of the Xiaoshi Lifei Decoction was slightly reddish in color, with an increased number of mucosal folds, and a reduced number of nodular protrusions on the mucosal surface and submucosal vascular branches. The results are shown in Figure 1 .

[0170] 2.2 Histopathological changes of gastric mucosa in rats of each group

[0171] like Figure 2As shown in A, under the light microscope, the gastric mucosal epithelial cells of the normal group rats were arranged neatly, the glands were regular in shape and densely arranged, the cell cytoplasm was rich and the color was uniform, there was no reduction in glands and goblet cells, and there was no significant inflammatory cell infiltration. The gastric mucosal cells of the model group rats were arranged disorderly, the glands in the lamina propria were significantly reduced, the glands were loose, the spaces between the glands became larger, inflammatory cell infiltration was visible in the interstitium, the mucosal layer became thinner, and the mucosal muscular layer became thicker. Compared with the model group, the number of glands in the gastric mucosal lamina propria of rats in the folic acid group and the low-, medium-, and high-dose groups of the Xiaoshi Lipi Recipe increased, the mucosal layer became thicker, and the mucosal muscular layer became thinner. Among them, the improvement in the medium-dose group of the Xiaoshi Lipi Recipe was the most significant.

[0172] like Figure 2 As shown in B, AB-PAS staining showed large blue-stained foci in the gastric mucosal lamina propria of rats in the model group, and the epithelial layer showed purple staining. Compared with the model group, the blue-stained foci in the gastric mucosal lamina propria and the purple-stained epithelial layer of rats in the folic acid group and the low-, medium-, and high-dose groups of the Xiaoshi Lifei Formula decreased in size and became lighter in color. Among them, the most significant improvement was seen in the medium-dose group of the Xiaoshi Lifei Formula.

[0173] 2.3 Comparison of serum gastrointestinal hormone indexes in rats of each group

[0174] Results Figure 3 Compared with the model group, the low-dose, medium-dose and high-dose groups of Xiaoshi Lifei Formula increased the levels of serum PGⅠ, PGR, G-17 and MTL, and decreased the level of PGⅡ in rats.

[0175] 2.4 Comparison of serum inflammatory factor-related indicators in rats of each group

[0176] Results Figure 4 Compared with the model group, the low-dose, medium-dose and high-dose groups of Xiaoshi Lifei Formula all reduced the serum IL-1β, IL-6 and TNF-α levels in rats.

[0177] 2.5 Comparison of serum oxidative stress-related indicators in rats of each group

[0178] Results Figure 5 Compared with the model group, the low-dose, medium-dose and high-dose groups of Xiaoshi Lifei Formula increased the levels of serum SOD, GSH and GSH-Px, and decreased the level of MDA in rats.

[0179] Experimental Example 3 Typical Case

[0180] Cai, male, 65 years old, was diagnosed with "upper abdominal discomfort for more than 1 year" on September 27, 2022. The patient drank alcohol for a long time, ate spicy food, had a history of fatty liver disease, and had upper abdominal discomfort 1 year ago, burning at night, accompanied by belching, worse after eating, no nausea, vomiting, no hematemesis, black stools, and took Western medicine (unknown) on his own. The symptoms were relieved, but still recurred. On September 10, 2022, he went to Dongguan Hospital of Guangzhou University of Chinese Medicine for a gastroscopy to take a biopsy of the gastric antrum tissue. Pathology showed chronic inflammation (++), active inflammation (-), atrophy (+++), and intestinal metaplasia (+++). Current symptoms: upper abdominal distension and discomfort, noisy feeling, belching, poor appetite, fatigue, general sleep, and normal bowel movements. The tongue is pale with white greasy fur, and the pulse is stringy and slippery. The Chinese medicine composition of Example 1 is used for treatment, one dose per day, divided into morning and evening. Two weeks later, the patient's stomach was slightly bloated, the noise was relieved, the food tasted good, and the belching occurred occasionally. He continued to take this prescription. After taking it for 3 months, the patient's gastroscopy showed superficial gastritis, and there was no recurrence during follow-up until 2024.

[0181] The above results show that the Chinese medicine composition of the present invention has a therapeutic effect on patients with precancerous conditions of the stomach, and can significantly improve clinical symptoms such as fullness or dull pain in the stomach after eating, early satiety, belching, loss of appetite, fatigue, intestinal borborygmus, etc., reverse gastric mucosal atrophy and intestinal metaplasia, and reduce the risk of gastric cancer.

[0182] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. A Chinese medicine composition for treating gastric precancerous condition, characterized in that: The invention comprises the following raw materials in parts by weight: 25-35 parts of fried malt, 25-35 parts of fried rice sprouts, 10-20 parts of chicken's gizzard lining, 15-25 parts of fried atractylodes macrocephala with bran, 6-15 parts of fried immature bitter orange with bran, 2-10 parts of agarwood, 10-20 parts of Eclipta prostrata, 6-15 parts of dendrobium, 6-15 parts of zedoaria, 10-20 parts of perilla stem and 2-10 parts of liquorice.

2. The Chinese medicine composition according to claim 1, characterized in that The weight ratio of the fried malt, fried rice sprouts and chicken's gizzard lining is 2:2:

1.

3. The Chinese medicine composition according to claim 1, characterized in that: The weight ratio of the fried Atractylodes macrocephala, fried Citrus aurantium and Aquilaria sinensis is 4:2:

1.

4. The Chinese medicine composition according to claim 1, characterized in that: The weight ratio of the Eclipta prostrata, Dendrobium officinale, Curcuma zedoaria and Perilla stem is 1.5:1:1:1.

5.

5. The Chinese medicine composition according to any one of claims 1 to 4, characterized in that: The Chinese medicine composition also includes pharmaceutically acceptable excipients, which include at least one of fillers, disintegrants, lubricants, suspending agents, adhesives, sweeteners, preservatives, and bases.

6. The Chinese medicine composition according to claim 5, characterized in that: The filler comprises at least one of starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose and sucrose; The disintegrant comprises at least one of starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, and cross-linked sodium carboxymethyl cellulose; The lubricant comprises: at least one of magnesium stearate, sodium lauryl sulfate, talc, and silicon dioxide; The suspending agent comprises: at least one of polyvinyl pyrrolidone, microcrystalline cellulose, sucrose, agar, and hydroxypropyl methylcellulose; The adhesive comprises: at least one of starch slurry, polyvinyl pyrrolidone and hydroxypropyl methylcellulose; The sweetener comprises: at least one of aspartame, xylitol, mannitol, sorbitol and sucrose; The preservative includes: at least one of sorbic acid, benzoic acid, sodium benzoate, and parabens; The matrix includes at least one of an oil-soluble matrix, an emulsion matrix, a water-soluble matrix, and an external ointment.

7. An oral dosage form drug for treating gastric precancerous conditions, characterized in that: The oral dosage form medicine comprises the Chinese medicine composition for treating gastric precancerous condition according to any one of claims 1 to 6; Preferably, the oral dosage form drug includes at least one of tablets, capsules, granules, pills, powders, and oral liquids.

8. Use of the Chinese medicine composition according to any one of claims 1 to 6 in the preparation of a drug for treating precancerous conditions of the stomach.

9. A method for preparing the Chinese medicine composition for treating gastric precancerous condition according to any one of claims 1 to 6, characterized in that: The steps include: S1. crushing the raw materials of the traditional Chinese medicine composition for treating gastric precancerous condition according to any one of claims 1 to 6 respectively, and mixing them into a composition according to the required weight parts; S2 extracting the composition of step S1 according to a conventional extraction method to obtain an extract; S3: the extract of step S2 is subjected to a refining and purification process to obtain an effective fraction, and the extract and the effective fraction are mixed to obtain the Chinese medicine composition for treating gastric precancerous condition; S4: further preparing the Chinese medicine composition of step S3 according to conventional preparation process to obtain a conventional oral dosage form.

10. The preparation method according to claim 9, characterized in that: The conventional extraction method of step S2 includes at least one of immersion extraction, decoction extraction, reflux extraction, percolation extraction, ultrasonic extraction, and microwave extraction; the refining and purification process of step S3 includes at least one of extraction, column chromatography separation, and high performance liquid chromatography separation; Preferably, the oral dosage form in step S4 includes at least one of tablets, capsules, granules, pills, powders, and oral liquids.

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