Traditional Chinese medicine composition for treating precancerous lesions of gastric cancer and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for treating gastric precancerous lesions. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 10-30 parts of astragalus membranaceus, 10-30 parts of radix pseudostellariae, 2-8 parts of pseudo-ginseng, 10-30 parts of oldenlandia diffusa, 5-20 parts of hericium erinaceus, 6-12 parts of bighead atractylodes rhizome, 10-15 parts of poria cocos and 6-9 parts of curcuma zedoary. And no gecko is included. The traditional Chinese medicine composition is reasonable in compatibility, can effectively treat atrophic gastritis, gastric mucosa intestinal metaplasia and gastric mucosa dysplasia, can prevent and treat gastric precancerous lesions, inhibits the transformation of gastritis to gastric cancer, and can effectively delay / block the process of transforming gastric precancerous lesions to gastric cancer vicious. In addition, the traditional Chinese medicine composition is higher in safety, more suitable for being taken for a long time, lower in cost and more beneficial to clinical popularization, and has a very good application value.

Description

Technical Field

[0001] The present invention belongs to the technical field of Chinese medicine compositions, and more specifically, relates to a Chinese medicine composition for treating gastric precancerous lesions and its application. Background Art

[0002] Gastric cancer, as a malignant tumor, has the characteristics of high morbidity, high mortality, and low early diagnosis rate, which seriously affects people's health level. Therefore, finding an effective strategy for the prevention and treatment of gastric cancer has become an important issue that needs to be solved urgently. According to the Correa classic cascade reaction, the pathological process of gastric cancer development goes through non-atrophic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → gastric cancer. The risk of canceration in the three stages of atrophic gastritis, intestinal metaplasia, and dysplasia is high, so they are collectively referred to as gastric precancerous lesions (GPL). Blocking or delaying the progression of gastric precancerous lesions to gastric cancer and inhibiting gastritis-cancer transformation have become effective measures to prevent and treat gastric cancer.

[0003] According to ancient medical records and modern TCM scholars' research on TCM, TCM has certain advantages in the understanding and treatment of gastric precancerous lesions. TCM believes that gastric precancerous lesions belong to the category of "stomach distension", which is mostly a mixed syndrome of deficiency and excess. Spleen deficiency and blood stasis are the key pathogenesis of this disease. In the process of gastric precancerous lesions, spleen and stomach weakness runs through the whole process of disease occurrence and development; the abundance of evil qi is an important condition for gastric precancerous lesions, and the inflammatory microenvironment formed by evil qi such as blood stasis and toxic stasis provides good conditions for the occurrence, development and metastasis of tumors. Therefore, spleen deficiency is the basic pathogenesis of gastric precancerous lesions, stasis is the central pathological link of gastric precancerous lesions, and toxicity is the final pathological product of gastric precancerous lesions. The overall pathogenesis is "deficiency, stasis and toxicity". For example, the research "Discussion on the pathogenesis of deficiency, stasis and toxicity in chronic atrophic gastritis and intervention of strengthening spleen, transforming blood and detoxification, Chinese Journal of Traditional Chinese Medicine, Pan Huafeng, 2012", "Discussion on gastric precancerous lesions from the perspective of cancer toxicity, Chinese Journal of Traditional Chinese Medicine, Li Haiwen, 2014" and so on.

[0004] The inventor team has developed a Chinese medicine composition for treating chronic atrophic gastritis (China authorized patent CN104888118B), the active ingredients of which are prepared from the following raw materials in parts by weight: 10-30 parts of Astragalus, 5-20 parts of Radix Pseudostellariae, 5-20 parts of Atractylodes macrocephalae, 5-20 parts of Poria cocos, 5-20 parts of Curcuma zedoariae, 2-10 parts of Gekko, 10-25 parts of Hedyotis diffusa, 10-25 parts of Monarda edodes, and 3-10 parts of Panax notoginseng. The Chinese medicine composition has a good effect in treating chronic atrophic gastritis, and therefore has a positive significance for preventing and treating gastric precancerous lesions, with a clinical effective rate of 86.7%. However, the cost of this prescription is relatively high, and the most notable one is the gecko (Chinese medicine name, also called palace guard), gecko (Gecko family, Gekko genus animal), and the cost of artificially breeding geckos is also relatively high; and geckos have certain toxicity. If used in excess, they may have certain effects on the nervous system and respiratory system, and are not suitable for long-term medication, and are not convenient for clinical promotion. However, the core mechanism of the Chinese medicine composition to prevent and treat chronic atrophic gastric precancerous lesions is to strengthen the spleen and replenish qi, detoxify and disperse knots, among which the key effect of gecko on detoxification and dispersing knots is the most critical, and it is crucial for the Chinese medicine composition to prevent and treat chronic atrophic gastric precancerous lesions. Existing research has also made it clear that geckos have the effects of dispelling wind, activating collaterals, dispersing knots, and detoxifying, and are commonly used for stroke paralysis, rheumatic joint pain, osteomyelitis, lymph node tuberculosis, esophageal cancer, lung cancer, primary liver cancer, intestinal cancer, etc. There are also studies showing that geckos are also commonly used in gastric cancer treatment "Research Progress of Gecko Treatment of Tumors, Yang Jinxia, ​​World Chinese Digestion Journal, 2006".

[0005] Therefore, how to solve the problem that the gecko in the above-mentioned traditional Chinese medicine composition plays a key role but has high cost and certain toxicity is of great significance for the treatment of gastritis patients and the prevention of gastric precancerous lesions. Summary of the invention

[0006] The present invention aims to further optimize the prescription in the Chinese authorized patent CN104888118B, solve the problem that the key ingredient gecko in the prescription is high in cost and has certain toxicity, and provide an optimized, cost-reduced, and safer traditional Chinese medicine composition for treating gastric precancerous lesions.

[0007] The first object of the present invention is to provide a Chinese medicine composition for preventing and treating gastric precancerous lesions.

[0008] The second object of the present invention is to provide pharmaceutical applications of the above-mentioned Chinese medicine composition.

[0009] The third object of the present invention is to provide a medicine for preventing and treating gastric precancerous lesions.

[0010] The above-mentioned purpose of the present invention is achieved through the following technical solutions:

[0011] After extensive exploration and research, the present invention deleted the gecko, and based on the key pathogenesis of "interaction of blood stasis and toxicity in the middle burner" of gastric precancerous lesions, the dosage ratio of other components was adjusted, including increasing the dosage of Pseudostellaria baicalensis and Poria cocos, and reducing the dosage of Panax notoginseng and Hericium erinaceus, so as to enhance the qi-invigorating effect of the prescription and improve the effectiveness of the prescription. The optimized prescription is safer and the cost is significantly reduced. Compared with the original prescription, it has greater application value and better market prospects.

[0012] Therefore, the present invention claims the following solutions:

[0013] The invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 10-30 parts of astragalus, 10-30 parts of pseudoginseng, 2-8 parts of notoginseng, 10-30 parts of oldenlandia diffusa, 5-20 parts of hericium erinaceus, 6-12 parts of atractylodes, 10-15 parts of tuckahoe, and 6-9 parts of zedoaria; and does not include geckos.

[0014] As a specific preferred embodiment, the traditional Chinese medicine composition for treating gastric precancerous lesions is composed of the following raw materials in parts by weight: 10-30 parts of Astragalus, 10-30 parts of Pseudostellaria, 2-8 parts of Panax notoginseng, 10-30 parts of Oldenlandia diffusa, 5-20 parts of Hericium erinaceus, 6-12 parts of Atractylodes macrocephala, 10-15 parts of Poria, and 6-9 parts of Curcuma.

[0015] More preferably, the Chinese medicine composition for treating gastric precancerous lesions is composed of the following raw materials in parts by weight: 20 parts of Astragalus, 15 parts of Radix Pseudostellariae, 3 parts of Panax Notoginseng, 15 parts of Hedyotis diffusa, 10 parts of Hericium erinaceus, 10 parts of Atractylodes macrocephala, 12 parts of Poria, and 9 parts of Curcuma. Based on a profound understanding of the pathological process of the disease and the theory of traditional Chinese medicine, the present invention emphasizes that in the treatment of gastric precancerous lesions during the pathological period, it is necessary not only to pay attention to the protection of the spleen, but also to pay attention to the important position of removing blood stasis and removing blood stasis in the treatment. The prescription of the Chinese medicine composition of the present invention is explained as follows:

[0016] Astragalus: A perennial herbaceous plant of the genus Astragalus in the Leguminosae family. The root of Astragalus is used as medicine, which is sweet and slightly warm in nature. It has the effects of replenishing qi and strengthening the exterior, resisting bacteria, expelling toxins, draining pus, and promoting tissue regeneration.

[0017] Pseudostellaria heterophylla: It is the dried root of Pseudostellaria heterophylla (Miq.) Pax ex Paxet Hoffm. of Caryophyllaceae. It is sweet, slightly bitter and flat in nature. Pseudostellaria heterophylla contains amino acids, polysaccharides, saponins, flavonoids and triterpenoids, and has the effects of invigorating qi and strengthening spleen, promoting body fluid and moistening lungs.

[0018] Panax notoginseng: The dried root of Panax notoginseng (Burk.) FHChen of the Araliaceae family. It has the effects of removing blood stasis and stopping bleeding, promoting blood circulation and relieving pain. It is mainly used to treat bleeding, traumatic injuries, and blood stasis and swelling.

[0019] Hedyotis diffusa: Rubiaceae, Hedyotis diffusa, annual loose herb. Bitter, light, cold in nature, with the functions of clearing away heat and detoxifying, relieving pain and dispersing stagnation, and promoting diuresis and removing dampness.

[0020] Hericium erinaceus: A fungus of the family Odontaceae and the genus Hericium. It is sweet and mild in nature, beneficial to the five internal organs and aids digestion. Network pharmacology studies have found that Hericium erinaceus has the effects of enhancing immune function, inhibiting tumors, and resisting ulcers.

[0021] Atractylodes: The dried rhizome of Atractylodes macrocephala (scientific name: Atractylodes macrocephala Koidz.) of the Asteraceae family. It tastes sweet and slightly spicy, and has the functions of strengthening the spleen and replenishing qi, drying dampness and promoting diuresis.

[0022] Poria cocos: It is the dried sclerotium of the Polyporaceae fungus Poria cocos (Schw.) Wolf. It tastes sweet and light, and is neutral in nature. It has the functions of promoting diuresis and eliminating dampness, strengthening the spleen and calming the mind.

[0023] Curcuma: A perennial herbaceous plant of the genus Curcuma in the ginger family. It tastes bitter and pungent, is warm in nature, and has the functions of promoting qi and removing blood, eliminating accumulation and relieving pain. Modern network pharmacology research has found that Curcuma has anti-tumor, anti-inflammatory, antiviral, and antibacterial pharmacological effects.

[0024] The results of animal experiments and clinical experiments of the present invention show that the Chinese medicine composition can be used to treat atrophic gastritis, gastric mucosal intestinal metaplasia, gastric mucosal dysplasia, prevent and treat gastric precancerous lesions, inhibit the transformation of gastritis to gastric cancer, and effectively delay / block the process of malignant transformation of gastric precancerous lesions to gastric cancer. Therefore, the present invention also claims the following application schemes:

[0025] Application of the above Chinese medicine composition in preparing medicine for preventing or treating atrophic gastritis.

[0026] Use of the above-mentioned Chinese medicine composition in preparing a drug for preventing or treating gastric mucosal intestinal metaplasia.

[0027] Use of the above-mentioned Chinese medicine composition in preparing a medicine for preventing or treating gastric mucosal dysplasia.

[0028] Application of the above-mentioned Chinese medicine composition in the preparation of a drug for preventing or treating gastric precancerous lesions.

[0029] Application of the above Chinese medicine composition in preparing medicine for inhibiting transformation of gastritis to gastric cancer.

[0030] The use of the above-mentioned Chinese medicine composition in the preparation of a drug for blocking and / or reversing the pathological process of gastric cancer; the pathological process of gastric cancer includes the transformation of chronic atrophic gastritis to gastric precancerous lesions and / or the transformation of gastric precancerous lesions to gastric cancer.

[0031] The present invention provides a medicine, which contains the above-mentioned Chinese medicine composition and pharmaceutically acceptable auxiliary materials.

[0032] The present invention has the following beneficial effects:

[0033] The formula of the Chinese medicine composition of the present invention is the most reasonable formula obtained after a lot of exploration and animal experimental research, as well as repeated clinical application and practice. Various drugs cooperate with each other in terms of efficacy, maximize the effect of treating gastric precancerous lesions, strengthen the spleen and replenish qi, remove blood stasis and detoxify, and are highly consistent with the inherent pathogenesis of gastric precancerous lesions. The clinical effective rate is 93.33%.

[0034] The present invention starts from the toxicology of the formula of the Chinese medicine composition. Gastric precancerous lesions are a common chronic disease in clinical practice, and the medication cycle is long. However, the gecko contained in the composition previously applied for by this research team has certain toxicity, and according to clinical studies, most patients with gastric precancerous lesions have weak constitutions, so it is not suitable for long-term use. The present invention re-explores and optimizes the formula, which no longer requires the gecko as a medicinal material, is more in line with clinical practice, and is suitable for patients to take for a long time.

[0035] The present invention starts from the cost of the formula of the Chinese medicine composition. Gastric precancerous lesions are a common chronic disease in clinical practice, and the medication cycle is long. The unit price of the gecko contained in the composition previously applied for by this research team is relatively high, which is easy to cause economic burden on patients and affect clinical promotion. The present invention not only affects the clinical efficacy but also improves the efficacy to a certain extent. It deletes the gecko as a medicinal material, reduces the cost of the composition formula, reduces the economic burden on patients, and is more conducive to clinical promotion.

[0036] The formula of the Chinese medicine composition of the present invention can effectively improve the clinical symptoms of patients with gastric precancerous lesions and delay / block the pathological process of gastric precancerous lesions. It has higher safety, is more suitable for long-term use, has lower cost, and has good application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 Figure 2 shows the HE staining results of gastric tissues of mice in each group.

[0038] Figure 2 The AB-PAS staining results of gastric tissues of mice in each group.

[0039] Figure 3 Figure 2 shows the PCR detection results of molecular markers of gastric precancerous lesions in gastric tissues of mice in each group (Figure a shows the qPCR detection results of AMACR gene; Figure b shows the qPCR detection results of MUC2 gene; Figure c shows the qPCR detection results of Ki67 gene).

[0040] Figure 4 This is the total score of TCM symptoms of patients at different periods.

[0041] Figure 5 This is the gastroscopy diagnosis result of Case 1.

[0042] Figure 6 These are the results of gastroscopy for patient 2.

[0043] Figure 7 These are the pathological examination results of case 2. DETAILED DESCRIPTION

[0044] The present invention is further described below in conjunction with the accompanying drawings and specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0045] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0046] In the following examples, mice were SPF-grade male C57BL / 6J mice with an initial body weight of 16-18 g and 5 weeks of age, purchased from Guangdong Medical Experimental Animal Center and raised in the SPF-grade Experimental Animal Center of Sanyuanli Campus of Guangzhou University of Chinese Medicine.

[0047] Methylnitrosourea (MNU), CAS No. 684-93-5, structural formula: Purchased from MacLean Reagent Company, catalog number N837326.

[0048] Vimesu tablets were purchased from Yilong Pharmaceutical Co., Ltd., with the national drug approval number: H41024769.

[0049] The methods of HE staining and AB-PAS staining in the following examples are based on the reference "Liu Wei. Study on the molecular mechanism of Weibiling regulating mTOR / HIF-1α / SIRT6 signaling pathway to mediate aerobic glycolysis in gastric precancerous lesions [D]. Guangzhou University of Chinese Medicine, 2019."

[0050] Example 1 A compound Chinese medicine for treating gastric precancerous lesions and inhibiting gastritis-cancer transformation

[0051] A compound Chinese medicine for treating gastric precancerous lesions, comprising the following ingredients by weight: 20 grams of astragalus, 15 grams of pseudoginseng, 3 grams of notoginseng, 15 grams of oldenlandia diffusa, 10 grams of atractylodes, 12 grams of tuckahoe, 9 grams of zedoaria, and 10 grams of hericium erinaceus.

[0052] Example 2 A compound Chinese medicine for treating gastric precancerous lesions and inhibiting gastritis-cancer transformation

[0053] A compound Chinese medicine for treating gastric precancerous lesions, comprising the following ingredients by weight: 20 grams of astragalus, 20 grams of pseudoginseng, 3 grams of notoginseng, 15 grams of oldenlandia diffusa, 10 grams of atractylodes, 12 grams of poria, 9 grams of zedoaria, and 10 grams of hericium erinaceus.

[0054] Example 3 A compound Chinese medicine for treating gastric precancerous lesions and inhibiting gastritis-cancer transformation

[0055] A compound Chinese medicine for treating gastric precancerous lesions, comprising the following ingredients by weight: 30 grams of Astragalus, 15 grams of Radix Pseudostellariae, 3 grams of Panax Notoginseng, 15 grams of Hedyotis diffusa, 10 grams of Atractylodes macrocephala, 12 grams of Poria, 9 grams of Curcuma, and 10 grams of Hericium erinaceus.

[0056] Example 4 Animal Experimental Study on the Compound Chinese Medicine for Treating Gastric Precancerous Lesions and Inhibiting Gastritis-Cancer Transformation

[0057] 1. Experimental Materials

[0058] 66 SPF male C57BL / 6J mice, with an initial body weight of 16-18 g and 5 weeks of age, were purchased from the Guangdong Medical Experimental Animal Center and raised in the SPF Experimental Animal Center of the Sanyuanli Campus of Guangzhou University of Chinese Medicine. This experiment passed the ethics review of the Ethics Committee of Guangzhou University of Chinese Medicine (approval number: 20230208008).

[0059] Chinese medicinal materials: Astragalus, Pseudostellaria heterophylla, Panax notoginseng, Hedyotis diffusa, Hericium erinaceus, Atractylodes macrocephala, Poria cocos, Curcuma zedoaria, all of which were purchased from Kangmei Pharmaceutical.

[0060] 2. Experimental Methods

[0061] 1. Establishment of a mouse model of gastric precancerous lesions

[0062] After one week of adaptive feeding, 66 mice were divided into a blank group (n=6) and a modeling group (n=60) by random number table method. The mice in the modeling group drank 120μg / mL MNU freely, and the modeling was carried out for 12 weeks. Two mice in the modeling group were randomly selected at week 12, and the stomach tissue was immediately removed after being killed for routine HE staining. Under the light microscope, the intrinsic glands were reduced, the arrangement was disordered, the inflammatory cells were infiltrated, and the nuclear-cytoplasmic ratio was increased, which confirmed that the modeling was successful.

[0063] 2. Preparation of Chinese medicine compound freeze-dried powder

[0064] According to the components and proportions of the compound Chinese medicine in Example 1, add the Chinese medicine to a 200L tilting reaction pot, add 10 times the amount of water, soak for 30min-1h, start heating, start timing after the water boils, and after 1h, serve the liquid medicine, filter it through a 100-mesh filter, and set it aside; add 8 times the amount of water, continue heating, and after 1h, serve the liquid medicine, filter it through a 100-mesh filter, and discard the residue. Combine the liquid medicine obtained from the first and second extractions, and use a rotary evaporator to concentrate the extract to obtain a Chinese medicine concentrate. The concentrate is placed in a 4°C environment overnight. Subsequently, the concentrate is placed in a freeze dryer for freeze-drying. After it is completely dried, it is powdered in a dry environment, and the powder is sieved through a 100-mesh sieve to obtain the compound Chinese medicine freeze-dried powder of Example 1.

[0065] 3. Intragastric administration of Chinese medicine compound to each group of mice

[0066] The mice with successful modeling were randomly divided into a model group (Model), a Vit group (Vit), a high-dose group of the compound Chinese medicine of Example 1 (JP-H), a medium-dose group of the compound Chinese medicine of Example 1 (JP-M), and a low-dose group of the compound Chinese medicine of Example 1 (JP-L), with 12 mice in each group, and continuous gavage administration. The Vit group was gavaged at 0.2 g / kg (1 times the clinical equivalent dose), and the high, medium, and low-dose groups of the compound Chinese medicine of Example 1 were gavaged at 15, 7.5, and 3.75 g / kg (1, 0.5, and 0.25 times the clinical equivalent dose), respectively. The blank group and the model group were gavaged with an equal volume of distilled water, once a day, for 10 consecutive weeks. Fasting was started 24 hours before the end of the experiment, but water was not allowed. The mice were killed, and the whole stomach was taken out by laparotomy. Gastric mucosa at the junction of the lesser curvature and antrum was obtained. Part of it was fixed and routinely paraffin-sectioned for HE and AB-PAS staining; the other part was stored at -80℃ awaiting RNA extraction and qPCR detection of molecular marker genes for gastric precancerous lesions (AMACR, MUC2, Ki67).

[0067] 2. Experimental Results

[0068] HE staining results of gastric tissues of mice in each group are shown in Figure 1 As shown, the results showed that the gastric mucosa of the blank group mice was in normal morphology; the gastric mucosal lamina propria glands of the model group (Model) mice were atrophied, the cells were disordered, the shapes and sizes were different, the nuclei were darkly stained, and the nuclear-cytoplasmic ratio was increased; after treatment with the compound Chinese medicine in Example 1, the gastric mucosal glands of the JP-H group, JP-M group and JP-L group mice were arranged relatively neatly, the glands were of moderate thickness, the shapes were regular, the degree of gastric mucosal atrophy was reduced, the staining was uniform, and the effect was gradually obvious with the increase of the dose; while the gastric mucosal arrangement and cell morphology of the vit group (Vit) mice were improved, but the degree of improvement was not as good as that of the JP-H group, JP-M group and JP-L group.

[0069] The results of AB-PAS staining of gastric tissues of mice in each group are shown in Figure 2As shown, the results show that AB-PAS staining can show intestinal metaplasia. The gastric mucosa of mice in the blank group was stained red, and no blue-stained area appeared, indicating that the mice had no intestinal metaplasia; the gastric mucosa of mice in the model group had obvious blue-stained areas and the staining was darker, indicating that the model group mice had intestinal metaplasia; after treatment with the compound Chinese medicine in Example 1, the blue-stained areas of mice in the JP-H group, JP-M group and JP-L group were reduced, and with the increase of the dose, the reduction of some blue-stained areas was gradually obvious; while the blue-stained areas of the gastric mucosa of mice in the vitase group were reduced, but the reduction effect was not as good as that of the JP-H group, JP-M group and JP-L group.

[0070] The results of qPCR detection of gastric precancerous lesion molecular markers in gastric tissues of mice in each group are as follows Figure 3 As shown, the results showed that compared with the normal group mice, the gene expression levels of molecular markers of gastric precancerous lesions such as AMACR, MUC2, and Ki67 in the model group mice were increased; compared with the model group mice, the expression of the above genes in the JP-H group, JP-M group, JP-L group and vitaminosis group mice were decreased, and the effect in the JP-H group was the most obvious.

[0071] Experimental Example 5 Clinical Experimental Study on Compound Chinese Medicine for Treating Gastric Precancerous Lesions and Inhibiting Gastritis-Cancer Transformation

[0072] 1. Clinical Data

[0073] The cases selected for this study were 15 outpatients who visited the First Affiliated Hospital of Guangzhou University of Chinese Medicine from March to September 2024 and were diagnosed with chronic atrophic gastritis (including chronic atrophic gastritis with intestinal metaplasia and chronic atrophic gastritis with dysplasia) by Western medicine and were diagnosed with spleen deficiency and dampness syndrome by TCM.

[0074] 2. Diagnostic Criteria

[0075] 1. Western medicine diagnostic criteria

[0076] Refer to the "Chinese Integrated Clinical Management Guidelines for Gastric Precancerous Lesions", "Consensus on the Diagnosis and Treatment of Chronic Atrophic Gastritis with Integrated Traditional Chinese and Western Medicine" (2017) and the CAG diagnostic criteria (trial) of the "Guidelines for Clinical Research of New Chinese Medicines".

[0077] Based on serological, endoscopic Kimura-Takemoto classification, and OLGA / OLGIM risk assessment, TCM syndromes can be incorporated to carry out risk monitoring and management of gastric precancerous lesions combining traditional Chinese and Western medicine.

[0078] (1) Gastroscopy diagnostic criteria:

[0079] ① Changes in mucosal color: During atrophy, the mucosal color is grayish white, grayish yellow, or gray; there is inconsistency in the depth of the mucosa in the same area, and the areas with strong red color also have grayish white. Generally, there may be slightly raised small red dots or erythema in the grayish yellow or grayish white areas; the range of atrophy may be diffuse, local, or focal, the mucosa becomes thinner and sunken, and the boundary is often not obvious.

[0080] ② Vascular visibility: Small blood vessels can be seen in the mucosa in the early stage of atrophy. In severe cases, dark red branch-like large blood vessels can be seen. The blood vessels at the gastric fundus and cardia can also be seen under normal circumstances.

[0081] ③ After atrophy, the glandular crypts may proliferate and elongate or undergo intestinal metaplasia, showing signs of overgrowth. The mucosal layer becomes thicker, and the blood vessels under the mucosa cannot be seen. The mucosal surface is rough and uneven, with granular or nodular stiffness.

[0082] Sufficient number, depth, and size of high-quality biopsies are important conditions for the accurate diagnosis and evaluation of gastric precancerous lesions.

[0083] (2) Pathological diagnostic criteria:

[0084] ① Atrophy of the intrinsic glands;

[0085] ②Thickening of the muscularis mucosa;

[0086] ③Intestinal metaplasia or pseudopyloric gland metaplasia;

[0087] ④Membrane propria inflammation;

[0088] ⑤ Lymph follicle formation.

[0089] (3) Disease classification standards

[0090] ① Grading standard for gastric mucosa endoscopic observation

[0091] Mild: Red and white, with white as the main color, and the vascular network is visible, often focal.

[0092] Moderate: Red and white, mainly white, with a clearly visible vascular network. Often diffuse, with flattened and shallow mucosal folds. Type B atrophy ranges from the antrum to the angle of the stomach.

[0093] Severe: In addition to the above manifestations, the mucosa is also granular or nodular. Type B atrophy extends to the middle and upper part of the stomach.

[0094] ② Pathological histological grading standard of glandular atrophy

[0095] Mild: The intrinsic glands are reduced by less than 1 / 3;

[0096] Moderate: The intrinsic glands are reduced by 1 / 3 to 2 / 3;

[0097] Severe: The intrinsic glands are reduced by more than 2 / 3.

[0098] ③ Histopathological grading standard of intestinal metaplasia

[0099] Mild: Intestinal surface epithelium and / or glands account for less than 1 / 3 of the total length of the mucosa;

[0100] Moderate: Intestinal surface epithelium and / or glands occupy 1 / 3 to 2 / 3 of the total length of the mucosa;

[0101] Severe: The intestinal surface epithelium and / or glands occupy more than 2 / 3 of the total length of the mucosa.

[0102] ④ Pathological histological grading standard of dysplasia (atypical hyperplasia)

[0103] Mild: The nucleus is slightly larger, darker, round, oval or columnar, densely arranged, and located at the base of the cell. In the case of gastric type, the epithelial cells are columnar and the mucus secretion is reduced; in the case of intestinal type, the goblet cells are reduced and Paneth cells are rare. The glandular ducts are slightly proliferative, the lumen is slightly irregular, the arrangement is slightly disordered and the density is uneven.

[0104] Moderate: Cell atypia is more obvious. The nuclei are enlarged, oval or rod-shaped, of varying sizes, densely stained, arranged in a disordered and uneven manner, with a pseudostratified structure, and frequent nuclear divisions. The epithelial cells are columnar, mucus secretion is significantly reduced, goblet cells are rare, and Paneth cells are not seen. The glandular ducts are densely arranged, with tortuous branches, irregular luminal structures, and varying shapes and sizes.

[0105] Severe: Cell atypia is very obvious, sometimes difficult to distinguish from well-differentiated mucosal endothelial carcinoma. Epithelial cells are tall columnar (intestinal type), goblet cells and Paneth cells are absent; or they are cuboidal and amorphous (gastric type), and the mucus secretion function disappears. The cell nuclei are significantly enlarged, with different sizes and shapes, disordered and uneven arrangement, increased nuclear / cell ratio, dark staining or loose reticular, obvious nucleoli, and common mitotic figures. The glandular duct structure is obviously disordered, with extremely irregular shape, size and arrangement, and common budding, branching, papillae, common walls and back-to-back phenomena.

[0106] 2. TCM diagnostic criteria

[0107] Refer to the diagnostic criteria for spleen and stomach qi deficiency syndrome in the "Expert Consensus on Traditional Chinese Medicine Diagnosis and Treatment of Chronic Gastritis (2023)".

[0108] (1) Main evidence

[0109] ① Distension or dull stomach pain;

[0110] ② Worsened after meals;

[0111] ③ Tiredness and weakness.

[0112] (2) Secondary Certificate

[0113] ① Poor appetite;

[0114] ② Tiredness of limbs;

[0115] ③Loose stool.

[0116] (3) Tongue and pulse

[0117] ① Pale tongue or with tooth marks, thin white fur;

[0118] ②Weak pulse.

[0119] Syndrome diagnosis: With 2 main symptoms and 2 secondary symptoms, the diagnosis can be made by referring to the tongue and pulse.

[0120] 3. Auxiliary examination

[0121] The four items of gastric function refer to the four scoring standards for gastric function in gastric cancer screening patients in the "Development and validation of a prediction rule forestimating gastric cancer risk in the Chinese high-risk population: anationwide multicentre study".

[0122] The hospital established a regression model based on factors significantly correlated with the risk of gastric cancer, such as the patient's age, gender, serum pepsinogen I / II (PG I / II) ratio, gastrin-17 (Gastrin-17), Helicobacter pylori urease antibody (Hp-Ab), and calculated four gastric function scores with a total score range of 0-25 points.

[0123] In this scoring system, the prevalence of gastric cancer was 1.2% in the low-risk (0-11 points) group, 4.4% in the medium-risk (12-16 points) group, and 12.3% in the high-risk (17-25 points) group, indicating that the higher the score, the greater the risk of gastric cancer.

[0124] 3. Inclusion and exclusion criteria for clinical cases:

[0125] 1. Inclusion criteria

[0126] (1) Aged between 18 and 72 (inclusive);

[0127] (2) Patients diagnosed with chronic atrophic gastritis (CAG) by gastroscopy and pathologically confirmed to have chronic atrophic gastritis with intestinal metaplasia (IM) and / or dysplasia (Dys);

[0128] (3) The patient provides informed consent, has good compliance, and cooperates voluntarily.

[0129] 2. Exclusion criteria

[0130] (1) Patients with serious primary diseases of important organs such as heart, lung, brain, liver, and kidney;

[0131] (2) Patients with upper gastrointestinal bleeding;

[0132] (3) Those who take nonsteroidal anti-inflammatory drugs for a long time;

[0133] (4) Patients suspected of having malignant lesions;

[0134] (5) Patients with peptic ulcer, gastroesophageal reflux disease, and gastric surgery;

[0135] (6) Patients with serious diseases of cardiovascular, cerebrovascular, liver, kidney, endocrine, immune system and blood system;

[0136] (7) Patients with severe mental illness;

[0137] (8) Women who are pregnant, intending to become pregnant or breastfeeding;

[0138] (9) Those who do not clearly describe their symptoms or the investigation is not consistent, do not take medication according to the prescribed method, cannot judge the efficacy, have incomplete data, etc., which affects the judgment of the efficacy;

[0139] (10) Except for patients with severe dysplasia.

[0140] 3. Criteria for exclusion and dropout of cases

[0141] (1) The subject fails to comply with the medication, increases, decreases, or stops taking medication on his / her own, or takes medication that is prohibited in this study, which affects the determination of efficacy and safety;

[0142] (2) the subjects failed to adhere to regular follow-up;

[0143] (3) The subject voluntarily withdraws from the study.

[0144] 4. Case termination criteria

[0145] (1) During the trial, the subject's condition worsens and he is not suitable to continue the trial;

[0146] (2) The subject is no longer suitable for the trial due to comorbidities or complications or special physiological changes.

[0147] 5. Ethical Review

[0148] The entire study complies with the Declaration of Helsinki and has been reviewed by the Ethics Committee. All patients need to understand the research methods and related precautions before enrolling for treatment. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, with approval number: NO.K

[2020] 144.

[0149] IV. Efficacy Standards

[0150] Formulated with reference to the "Guidelines for Clinical Research of New Chinese Medicines" (Trial).

[0151] 1. TCM symptom efficacy evaluation criteria

[0152] ①Clinical recovery: symptoms and signs disappear or almost disappear, and symptom score decreases by ≥95%;

[0153] ② Significantly effective: symptoms and signs are significantly improved, and the symptom score is reduced by ≥70%;

[0154] ③Effective: symptoms and signs are improved, and the symptom score is reduced by ≥30%;

[0155] ④ Ineffective: There is no significant improvement in symptoms and signs, or even aggravation, and the symptom score is reduced by less than 30%.

[0156] Note: Calculation formula (Nimodipine method): [(pre-treatment score - post-treatment score) ÷ pre-treatment score] × 100%

[0157] Total effective rate = (cured + markedly effective + effective) ÷ total number of cases × 100%.

[0158] 2. Evaluation of the efficacy of TCM main symptoms

[0159] ①Clinical control: after the treatment, the symptoms disappear;

[0160] ② Significantly effective: after the treatment, the symptom grade is reduced by 2 levels;

[0161] ③ Effective: After the treatment, the symptom grade is reduced by 1 level;

[0162] ④Invalid: Those who fail to meet the above standards.

[0163] 5. Statistical Methods

[0164] All data were entered into Excel and processed using SPSS29.0. Normality tests were performed before processing. Chi-square test was used for count data, nonparametric rank sum test was used for rank data, and t test was used for measurement data if they were in accordance with normal distribution, and nonparametric rank sum test was used if they were not in accordance with normal distribution. If P < 0.05, the difference was statistically significant.

[0165] 6. Treatment plan

[0166] 1. Treatment methods

[0167] 15 patients with clinical spleen deficiency and dampness accumulation type gastric precancerous lesions that met the acceptance and elimination criteria took the compound Chinese medicine (the patients took the compound Chinese medicine of Example 1, Example 2 or Example 3) once a day for a course of four weeks, and clinical observation and data statistical analysis were performed.

[0168] 2. Observation of efficacy indicators

[0169] (1) Clinical symptoms

[0170] The main symptoms and signs were stomachache, fullness in the stomach, refusal to press stomachache, poor appetite, belching and acid reflux, dry mouth and bitter taste, nausea and vomiting, dark complexion, constipation, pale or light red tongue, greasy or thick tongue coating, stringy and slow pulse, etc. The data were recorded once before taking the medicine, at the second weekend of taking the medicine, and at the fourth weekend of taking the medicine, for a total of 3 times. The TCM symptom classification and quantification were carried out in accordance with the "Guidelines for Clinical Research of New Chinese Medicines" (Trial). According to the symptoms of no, mild, moderate, and severe, the main symptoms were recorded as 0 points, 2 points, 4 points, and 6 points, respectively, and the secondary symptoms were recorded as 0 points, 1 point, 2 points, and 3 points. The tongue and pulse conditions were not scored (see Table 1).

[0171] Table 1 TCM symptom score table

[0172]

[0173]

[0174]

[0175] VII. Treatment Outcomes

[0176] 1. Total effective rate of clinical symptoms

[0177] The total clinical effective rate of the patients after treatment is shown in Table 2. The results show that after taking the medicine for 4 weeks, 1 of the 15 patients was cured, 7 were significantly effective, 6 were effective, and 1 was ineffective, with an effective rate of 93.33%. All patients taking Examples 1, 2, and 3 had effective cases.

[0178] Table 2 Total clinical efficacy of patients after treatment

[0179]

[0180] 2. The scores of TCM symptoms before and after treatment

[0181] The TCM symptom scores of the patients are shown in Table 3. The total TCM symptom scores of the patients at different stages are shown in Table 3. Figure 4 As shown, the results showed that the TCM symptom scores of patients 2 weeks and 4 weeks after treatment were significantly lower than those before treatment.

[0182] Table 3 The scores of TCM symptoms before and after treatment

[0183]

[0184]

[0185] Note: Data are expressed as M (P25, P75).

[0186] 3. Conclusion

[0187] The compound Chinese medicine of the present invention can effectively improve the atrophy of gastric mucosal glands in mice at the tissue level, reduce the intestinal metaplasia area, and can effectively downregulate the expression of molecular markers of gastric precancerous lesions at the molecular level; it can effectively alleviate the clinical symptoms of patients with gastric precancerous lesions, and can effectively improve the clinical symptoms of gastric precancerous lesions such as stomach pain, fullness in the stomach, belching, acid reflux, dry mouth and bitter taste, inhibit the gastritis-gastric cancer transformation process, and play a therapeutic effect on gastric precancerous lesions.

[0188] Experimental Example 6 Typical Case

[0189] 1. Case 1

[0190] He XX, female, 54 years old, first visited the hospital on April 15, 2024. The patient underwent gastroscopy and pathological examination on March 27, 2024, which showed chronic atrophic gastritis with erosion, mainly in the gastric antrum, and mild intestinal metaplasia of the glands ( Figure 5 ). At the first visit, the patient complained of recurrent right abdominal pain, red tongue with white fur, stringy pulse, and a score of 8 on the TCM symptom score table. After TCM syndrome differentiation, the patient was treated with 20 grams of Astragalus, 15 grams of Pseudostellariae Radix, 3 grams of Panax Notoginseng, 15 grams of Hedyotis Diffusa, 10 grams of Atractylodes, 12 grams of Poria, 9 grams of Curcuma, and 10 grams of Hericium erinaceus as the main prescription for addition and subtraction. After treatment, there was no obvious discomfort. The patient was re-examined every half month, and the symptoms of right abdominal pain gradually improved. After taking the medicine for 4 weeks, the TCM symptom score table was 2 points, indicating that the patient's clinical symptoms were alleviated.

[0191] Case 2

[0192] Min XX, female, 61 years old, first visited the hospital on April 15, 2024. The patient underwent gastroscopy and pathological examination on March 30, 2024, which showed severe chronic atrophic gastritis (gastric angle and gastric antral mucosa) with glandular intestinal metaplasia ( Figure 6 and Figure 7 ). At the first visit, the patient complained of epigastric distension and discomfort, accompanied by mild abdominal pain, belching and acid reflux, dry mouth and bitter taste, poor appetite, pale tongue with white fur, and stringy pulse; the TCM symptom score was 17 points. After TCM syndrome differentiation, the patient was treated with 20 grams of Astragalus, 15 grams of Pseudostellariae Radix, 3 grams of Panax Notoginseng, 15 grams of Hedyotis Diffusa, 10 grams of Atractylodes, 12 grams of Poria, 9 grams of Curcuma, and 10 grams of Hericium erinaceus as the main prescription for addition and subtraction. After treatment, there was no obvious discomfort. The patient was re-examined every half month, and the symptoms such as abdominal pain, distension, and poor appetite were significantly improved. After taking the medicine for 4 weeks, the patient had no other discomfort except mild epigastric distension and discomfort. The TCM symptom score was 2 points, indicating that the patient's clinical symptoms were alleviated.

[0193] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A Chinese medicine composition, characterized in that: The invention comprises the following raw materials in parts by weight: 10-30 parts of astragalus, 10-30 parts of pseudoginseng, 2-8 parts of panax notoginseng, 10-30 parts of oldenlandia diffusa, 5-20 parts of hericium erinaceus, 6-12 parts of atractylodes, 10-15 parts of poria, and 6-9 parts of zedoaria; and does not include geckos.

2. The Chinese medicine composition according to claim 1, characterized in that: The invention is composed of the following raw materials in parts by weight: 10-30 parts of astragalus, 10-30 parts of pseudoginseng, 2-8 parts of panax notoginseng, 10-30 parts of oldenlandia diffusa, 5-20 parts of hericium erinaceus, 6-12 parts of atractylodes, 10-15 parts of tuckahoe and 6-9 parts of zedoaria.

3. The Chinese medicine composition according to claim 2, characterized in that: The invention is composed of the following raw materials in parts by weight: 20 parts of astragalus, 15 parts of pseudoginseng, 3 parts of panax notoginseng, 15 parts of oldenlandia diffusa, 10 parts of hericium erinaceus, 10 parts of atractylodes, 12 parts of tuckahoe and 9 parts of zedoaria.

4. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a drug for preventing or treating gastric precancerous lesions.

5. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for preventing or treating atrophic gastritis.

6. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for preventing or treating intestinal metaplasia of gastric mucosa.

7. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for preventing or treating gastric mucosal epithelial dysplasia.

8. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for inhibiting the transformation of gastritis to gastric cancer.

9. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a drug for blocking and / or reversing the pathological process of gastric cancer; the pathological process of gastric cancer includes the transformation of chronic atrophic gastritis to gastric precancerous lesions and / or the transformation of gastric precancerous lesions to gastric cancer.

10. A drug, characterized in that Contains the Chinese medicine composition according to any one of claims 1 to 3 and pharmaceutically acceptable excipients.

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