Traditional Chinese medicine dill stomach-regulating powder for treating chronic atrophic gastritis

Abstract

The invention discloses a traditional Chinese medicine prescription for treating chronic atrophic gastritis, which is obtained by combining modern network pharmacology technology and traditional Chinese medicine experience, and comprises lotus leaf, buckeye, fried bighead atractylodes rhizome, radix astragali preparata, common yam rhizome, combined spicebush root, lysimachia christinae hance, calcined concha arcae and dandelion. The traditional Chinese medicine composition is used for treating chronic atrophic gastritis inflammation, reversal of gastric mucosal lesion, inhibition of intestinal metaplasia, prevention of gastritis cancer transformation and the like. The traditional Chinese medicine composition has the treatment effects of invigorating spleen to eliminate dampness, clearing heat and removing stasis, and is mainly used for treating chronic atrophic gastric inflammation such as gastral cavity fullness, gastral cavity scorching heat and pain, poor appetite, weakness and limb fatigue, noisy and acid regurgitation and the like.

Description

Technical Field

[0001] The present invention relates to a traditional Chinese medicine for treating chronic atrophic gastritis, belonging to the technical field of traditional Chinese medicine. Background Art

[0002] Chronic atrophic gastritis refers to a chronic gastric disease in which the gastric mucosa epithelium suffers repeated damage resulting in the reduction of intrinsic glands, with or without intestinal metaplasia and / or pseudopyloric gland metaplasia, and is also a common and frequently-occurring disease in the digestive medicine department. [1,2] . The clinical manifestations of patients with chronic atrophic gastritis are non-specific. They may have no obvious symptoms, or may show non-specific dyspeptic symptoms such as upper abdominal discomfort, fullness, pain, etc. Some patients may also have gastroesophageal reflux disease at the same time, manifested as acid reflux, heartburn, etc. Some patients may have manifestations of bile reflux, such as bitter taste in the mouth, noisy feeling, belching. However, the correlation between different endoscopic manifestations and the severity of their pathology and symptoms is not obvious. Gastric diseases seriously affect the physical health and quality of life of patients. The incidence of chronic gastritis in China shows an upward trend. [3] . The prevalence of chronic gastritis, especially chronic atrophic gastritis, generally increases with age. [4] . In recent years, studies have found that the occurrence of chronic gastritis, especially chronic atrophic gastritis, is closely related to Helicobacter pylori (HP) infection. [5-9] .

[0003] "Consensus on Chronic Gastritis in China (Shanghai, 2017)" points out that based on the etiology, chronic gastritis can be divided into HP gastritis and non-HP gastritis. The treatment of chronic gastritis should be as targeted at the etiology as possible and follow the principle of individualization. The purpose of treatment is to remove the etiology, relieve symptoms and improve the inflammatory reaction of the gastric mucosa [7]. The current Western medicine treatment mainly adopts the elimination of etiology and drug treatment. Since HP is an important etiology causing chronic gastritis, Western medicine treatment often combines anti-HP drugs. The ideal eradication regimen for HP should have a high HP eradication rate, be economical, simple, have no drug resistance, and no adverse reactions. However, there is currently no completely ideal regimen. [1,8,10] . Currently, the drugs for treating HP infection mainly include H2 receptor blockers, proton pump inhibitors (PPI), antibiotics (such as amoxicillin, clarithromycin, metronidazole, etc.) and bismuth agents (such as bismuth potassium citrate granules). The appropriate treatment should be selected according to factors such as the patient's condition, compliance and economic ability.

[11] . Clinically, a triple therapy based on PPI or bismuth agent is mostly adopted, and two of metronidazole, clarithromycin, amoxicillin are added, as well as the bismuth quadruple HP eradication regimen recommended by the Fifth Chinese Consensus on the Management of Helicobacter pylori Infection, that is, proton pump inhibitor (PPI) + bismuth agent + two antibacterial drugs. One month of Western medicine treatment is one course of treatment (when antibiotics are used in combination, antibiotics are usually used for 2 weeks and then discontinued), and the drug is discontinued or the course of treatment is extended as appropriate according to the patient's clinical symptoms and gastroscopy reexamination results.[8,11,12] However, relying solely on Western medicine for treatment cannot completely suppress the condition. Moreover, with the widespread use of antibiotics, the incidence of HP-resistant strains is continuously increasing, leading to higher treatment failure rates and recurrence rates after drug withdrawal. Therefore, it is urgent to explore a more effective treatment plan. [13,14] .

[0004] Chronic atrophic gastritis belongs to the category of "epigastric pain" in traditional Chinese medicine. The stomach functions smoothly in a descending manner physiologically and becomes diseased due to stagnation pathologically. According to traditional Chinese medicine theory, "the spleen and stomach are the foundation of the body, and qi and blood are the source of hematopoiesis. The spleen and stomach are exterior-interiorly related." In daily life, weakness of the spleen and stomach and improper diet are likely to cause chronic gastritis. At the same time, factors such as emotional disorders, drugs, and exogenous pathogens (Helicobacter pylori infection) are also important causes of chronic gastritis. These factors damage the spleen and stomach, resulting in disordered transportation and transformation, abnormal ascending and descending, and the occurrence of qi stagnation, damp obstruction, cold congelation, fire stagnation, blood stasis, etc., thus manifesting symptoms such as stomach pain and distension. Through long-term clinical practice, traditional Chinese medicine has formed certain advantages in the treatment of chronic gastritis. [15,16] .

[0005] Hesuo Tiaowei Powder is developed by the inventor using the "network target" method and the UNIQ patent system [17-20] Through analysis, by collecting the components and their chemical information contained in each traditional Chinese medicine, using the patent method drugCIPHER proposed by the inventor to predict the target list of each traditional Chinese medicine component; further, selecting the biological processes and biological pathways related to chronic atrophic gastritis, and constructing a chronic atrophic gastritis biomolecular network using the biomolecules and protein interactions in the above biological processes and pathways; using a statistical model to measure the importance of traditional Chinese medicine component targets in the efficacy of traditional Chinese medicine, and then calculating the overall target list of each traditional Chinese medicine. Conduct a biological function enrichment analysis on the overall target list of each traditional Chinese medicine, use Fisher's exact test to calculate the enrichment significance of each traditional Chinese medicine in each biological process and pathway in the network (P<0.05 is considered significant), and comprehensively rank the regulatory effects of traditional Chinese medicines on chronic atrophic gastritis as alternative traditional Chinese medicines. Then, combined with the rich clinical experience of the national master of traditional Chinese medicine, Mr. Li Jiren, and his academic successor, Li Yan (i.e., the inventor), screen the alternative traditional Chinese medicines according to traditional Chinese medicine theory to obtain the prescription. Summary of the Invention

[0006] According to one aspect of the present invention, there is provided a traditional Chinese medicine for treating chronic atrophic gastritis, which is characterized in that it is prepared from the following raw traditional Chinese medicines by weight: 12g of lotus leaf, 9g of Chinese sweetgum fruit, 15g of stir-fried Atractylodes macrocephala, 15g of roasted Astragalus membranaceus, 10g of Chinese yam, 12g of Lindera aggregata, 15g of Lysimachia christinae, 12g of calcined Concha Arcae, 15g of dandelion. Brief Description of the Drawings

[0007] Figure 1This is a schematic diagram of the staging and grading method of the operative link ongastritis assessment (OLGA) and the operative link for gastric intestinal metaplasia assessment (OLGIM) in the New Sydney system for chronic gastritis used in the pathological scoring of traditional Chinese medicine for treating chronic atrophic gastritis according to the present invention.

[0008] Figure 2 1 is a five-point histopathological result obtained according to the New Sydney System for chronic gastritis, showing the histopathological results of OLGA and OLGIM evaluation stages IV and IV at baseline, respectively, in one embodiment of the present invention.

[0009] Figure 3 The five-point histopathological results show that the patient was stage I and I respectively in OLGA and OLGIM evaluation stages after taking this Chinese medicine prescription for 6 months. DETAILED DESCRIPTION

[0010] The purpose of the present invention is to provide a traditional Chinese medicine prescription for treating chronic atrophic gastritis. The traditional Chinese medicine prescription has specific therapeutic effects in improving symptoms such as bloating, stomach pain, poor appetite, fatigue, noisy discomfort, etc. in patients with chronic atrophic gastritis, inhibiting Helicobacter pylori, reversing gastric mucosal damage, alleviating intestinal metaplasia or dysplasia, and preventing inflammation-cancer transformation.

[0011] According to one aspect of the present invention, a traditional Chinese medicine prescription for treating chronic atrophic gastritis is provided, which is prepared from the following raw materials, and the dosage of the medicine refers to the dosage specified in the "Chinese Pharmacopoeia", for example: 12g of lotus leaf, 9g of sarophora seed, 15g of stir-fried Atractylodes macrocephala, 15g of roasted Astragalus root, 10g of Chinese yam, 12g of Linderae scutellariae, 15g of Lysimachia scabra, 12g of calcined Corrugated Iron Fructus, and 15g of Taraxacum mongolicum. The above traditional Chinese medicine is taken in the form of a decoction, one dose per day, taken twice a day in the morning and evening, for a course of 6 months.

[0012] The main functions and mechanism of action of this Chinese medicine prescription:

[0013] Function: Strengthens the spleen and eliminates dampness, clears heat and disperses stagnation. Indications: Chronic atrophic gastritis with epigastric distension, epigastric pain, poor appetite, fatigue, limb tiredness, noisy and acid reflux.

[0014] Mechanism and Characteristics: Chronic atrophic gastritis, also known as "epigastric pain" in Traditional Chinese Medicine (TCM), is a condition characterized by physiological harmony and descending function. Pathologically, the stomach is affected by stagnation. Traditional Chinese Medicine (TCM) theory posits that the spleen and stomach are the foundation of the body, with qi and blood as the source of biochemical processes, and the spleen and stomach functioning as the exterior and interior of each other. Spleen and stomach deficiency and dietary irregularities in daily life can contribute to chronic gastritis. Emotional imbalance, medications, and exogenous pathogens (such as Helicobacter pylori infection) are also significant contributors. These factors damage the spleen and stomach, leading to dysfunctional transport and transformation, and abnormal ascending and descending functions, resulting in dampness obstruction, fire stagnation, qi stagnation, cold coagulation, and blood stasis, manifesting as stomach pain and bloating. The "Expert Consensus on the Diagnosis and Treatment of Chronic Gastritis in Traditional Chinese Medicine (2017)" states that the pathogenesis of chronic gastritis can be divided into two aspects: underlying deficiency and superficial excess. The underlying deficiency manifests primarily as spleen qi (yang) deficiency and stomach yin deficiency, while the superficial excess manifests primarily as damp-heat, qi stagnation, and blood stasis. Chronic atrophic gastritis is characterized by a long course of illness, with progressive deficiency of vital energy, internal generation of phlegm and dampness from spleen deficiency, which transforms into heat over time. This internal dampness and heat, combined with blood stasis, leads to pathological changes. This traditional Chinese medicine prescription, with stir-fried Atractylodes macrocephala, lotus leaf, and Salacia chinensis as the main ingredients, enhances the spleen-tonifying, damp-resolving, heat-clearing, and stagnation-dispersing properties.

[0015] Pharmacological efficacy and pharmacology of the raw materials of this Chinese medicine prescription:

[0016] This prescription uses lotus leaf and salvia officinalis seeds as the main herbs, with white atractylodes and astragalus as the auxiliary herbs. They coordinate their ascending and descending properties, balancing cold and heat, and collectively strengthen the spleen and stomach, regulating qi and dispersing stagnation. Compendium of Materia Medica and New Compendium of Materia Medica note that lotus leaf has the traditional effects of "benefiting the spleen and stomach, promoting vital energy, quenching thirst, promoting salivation, and relieving internal heat." Lotus leaf is widely used in functional foods, health foods, and solid beverages. Modern research suggests that lotus leaf has new therapeutic effects in treating chronic atrophic gastritis with intestinal metaplasia or dysplasia. Salvia officinalis seeds have the functions of relieving fullness and regulating qi, killing insects, dispelling cold and relieving pain. "Compendium of Materia Medica" states: "It relieves fullness and lowers qi, treats epigastric, liver, and diaphragmatic distension, malnutrition, dysentery, hematemesis, fatigue, and soothes the stomach and dredges the meridians." The auxiliary herb, stir-fried Atractylodes macrocephala, tonifies qi and strengthens the spleen, eliminates dampness and promotes diuresis; roasted Astragalus root enters the spleen and lung meridians, strengthening the spleen and replenishing the middle; Chinese yam enters the spleen, lung, and kidney meridians, nourishing the kidneys and strengthening the spleen. These three herbs enhance the main herb's function of strengthening the foundation and nourishing the vital energy. Centella asiatica and dandelion enter the liver, stomach, and gallbladder meridians, clearing heat and dampness, detoxifying and reducing swelling; Linderae scutellariae promotes qi and relieves pain, warming the kidneys and dispelling cold. Modern pharmacological research shows that Centella asiatica and dandelion have inhibitory effects on Helicobacter pylori. Scutellaria baicalensis seeds resolve phlegm, soften hard masses, and relieve acid and pain. Modern research indicates that patients with chronic atrophic gastritis experience glandular atrophy. Calcined Scutellaria baicalensis seeds can be used as a counter-acting acid suppressant, promoting gastric acid secretion and inhibiting further glandular atrophy. This prescription is properly combined to strengthen the spleen and eliminate dampness, clear away heat and disperse nodules.

[0017] This Chinese medicine prescription is modified and applied:

[0018] For patients with long-term illness and insufficient qi and blood, symptoms include shortness of breath, fatigue, lack of breath, laziness to speak, and pale complexion. Add Codonopsis pilosula and Chinese angelica to replenish qi and nourish blood.

[0019] The determination process of the Chinese medicine prescription of the present invention includes (but is not limited to) the following tasks:

[0020] 1) Information such as the components, chemical structures, and CID numbers of each traditional Chinese medicine were manually collected from the literature (source: PubChem database), and the "network target" theory and method pioneered by the inventor were used [17，18] to analyze the mechanism of action of traditional Chinese medicine prescriptions on gastric diseases;

[0021] 2) Use the patented method based on network targets proposed by the inventor [19-20] drugCIPHER to predict the target list of each traditional Chinese medicine component;

[0022] 3) Select biological processes and pathways related to chronic atrophic gastritis; construct a biomolecular network similar to chronic gastritis using biomolecules and protein interactions in the above biological processes and pathways;

[0023] 4) Use a statistical model to measure the importance of traditional Chinese medicine component targets in the efficacy of traditional Chinese medicine, and then calculate the overall target list of each traditional Chinese medicine;

[0024] 5) Conduct a biological function enrichment analysis on the overall target list of each traditional Chinese medicine, use Fisher's exact test to calculate the enrichment significance of each traditional Chinese medicine in each biological process and pathway in the network (P<0.05 is considered significant), and comprehensively rank the regulatory effects of traditional Chinese medicine on chronic atrophic gastritis as alternative traditional Chinese medicines.

[0025] 6) Combine the clinical experience of Master Li Jiren of traditional Chinese medicine and his academic heir Li Yan (the inventor), and screen the alternative traditional Chinese medicines according to the theory of traditional Chinese medicine to obtain an optimized prescription;

[0026] 7) Apply the optimized prescription for clinical experimental observation and verification.

[0027] Comparison of this traditional Chinese medicine prescription with traditional Chinese patent medicines for treating chronic atrophic gastritis:

[0028] The main features of this traditional Chinese medicine prescription compared with traditional Chinese patent medicines for treating chronic atrophic gastritis are as follows:

[0029] It is used to treat chronic atrophic gastritis by targeting the inflammatory response, inhibiting Helicobacter pylori, reversing gastric mucosal lesions, and preventing the transformation of inflammation to cancer. By inhibiting further atrophy of glands and improving or reversing gastric mucosal lesions, the purpose of improving symptoms and treating diseases is achieved.

[0030] This traditional Chinese medicine prescription applies the "network target" technology method, targets the "pathways related to chronic atrophic gastritis", predicts effective drugs for treatment, and is guided by the idea of syndrome differentiation and treatment in traditional Chinese medicine. Combining the clinical experience of Master Li Jiren of traditional Chinese medicine, an optimized prescription is obtained. Its drug components treat this disease from multiple aspects such as inhibiting inflammatory responses, inhibiting Helicobacter pylori, improving gastric mucosal lesions, and inhibiting intestinal metaplasia or dysplasia of the stomach.

[0031] This prescription inherits the academic thought of strengthening the root and cultivating the primordial qi of the Xin'an medical school, with lotus leaf and Chinese sweetgum fruit as the monarch drugs. It is recorded in Compendium of Materia Medica and New Compendium of Materia Medica that lotus leaf has the traditional effects of "benefiting the spleen and stomach, promoting the growth of primordial qi, quenching thirst and generating body fluid, and relieving fire heat". Modern pharmacological research suggests that lotus leaf extract and nuciferine can effectively block the proliferation of gastric cancer-transformed cells, reverse gastric mucosal lesions, and protect gastric mucosal damage.

[24] Chinese sweetgum fruit is a traditional Chinese medicine included in the Chinese Pharmacopoeia. According to traditional Chinese medicine theory, this product is warm in nature, sweet in taste, and belongs to the liver and stomach meridians, with the effects of regulating qi and relieving distension, and killing insects. Clinically, it is mostly used for the treatment of chest and abdominal distension, epigastric pain and other symptoms. Modern pharmacological research has confirmed that the main active ingredient of this product, aescin, has the effects of promoting gastric emptying, inhibiting gastric acid secretion, down-regulating inflammatory injury factors, and protecting the gastric mucosa. [21-23] 。

[0032] The following further details this traditional Chinese medicine prescription in combination with examples.

[0033] Test method: A traditional Chinese medicine prescription for treating chronic atrophic gastritis is prepared from the following raw traditional Chinese medicines: 12 g of lotus leaf, 9 g of Chinese sweetgum fruit, 15 g of stir-fried Atractylodes macrocephala, 15 g of roasted Astragalus membranaceus, 10 g of Chinese yam, 12 g of Lindera aggregata, 15 g of Lysimachia christinae, 12 g of calcined Concha Arcae, and 15 g of Taraxacum mongolicum. The above traditional Chinese medicines are uniformly provided with relevant medicinal materials by the traditional Chinese medicine pharmacy of Yijishan Hospital of Wannan Medical College. One dose is taken daily, divided into two times in the morning and evening, and one course of treatment is for 6 months. Observe one course of treatment. Evaluate the scores of traditional Chinese medicine symptoms and signs, and the gastroscopy pathological scores, and make a comparison before and after treatment.

[0034] Efficacy evaluation criteria: Refer to the Guidelines for Clinical Research of New Traditional Chinese Medicines to judge the patients. Recovery: After treatment, the clinical symptoms and signs of traditional Chinese medicine of the patients basically disappear, and the syndrome score decreases by ≥ 95%; Marked effect: After treatment, the clinical symptoms and signs of traditional Chinese medicine of the patients are significantly improved, and the syndrome score decreases by ≥ 70%; Effective: After treatment, the clinical symptoms and signs of traditional Chinese medicine of the patients are partially improved, and the traditional Chinese medicine syndrome score decreases by ≥ 30%; Ineffective: After treatment, the clinical symptoms and signs of traditional Chinese medicine of the patients have no improvement, or even worsen, and the syndrome score decreases by < 30%. Therefore, 30% is taken as the effective change index in the subjective scoring index. Pathological scoring criteria [25，26] : Refer to the operative link on gastritis assessment (OLGA) and the operative link for gastric intestinal metaplasia assessment (OLGIM) staging and grading methods in the new Sydney system of chronic gastritis (as Figure 1 shown).

[0035] Pathological scoring results: As shown in the following table, by comparing the data of 30 patients before and after treatment, both the OLGA score and the OLGIM score were significantly lower than those before treatment (P < 0.001), indicating that Hesuo Tiaowei Powder can effectively reverse the lesions of chronic atrophic gastritis.

[0036]

[0037] Example: The relevant medicinal materials of Hesuo Tiaowei Powder were provided by the Chinese medicine pharmacy of Yijishan Hospital, Wannan Medical College. One dose was taken daily, divided into two times, morning and evening, and one course of treatment was for 6 months.

[0038] Typical case:

[0039] Case: Mr. Xie, male, 38 years old, native place: Wuhu, Anhui. First diagnosis on April 11, 2022. The gastroscopy diagnosis was "chronic atrophic gastritis". The initial enrollment time was: May 1, 2022. It met the diagnostic criteria of chronic atrophic gastritis. No other drugs were taken except this Chinese medicine prescription during the observation period.

[0040] After 6 months of taking the medicine, in the evaluation of traditional Chinese medicine syndrome evaluation indicators, the main symptoms of epigastric fullness and epigastric pain basically disappeared, and the secondary symptoms of poor appetite, fatigue, and discomfort of stomach upset were significantly improved compared with those before treatment. The total score of traditional Chinese medicine clinical symptoms was significantly lower than that before treatment; rechecking gastroscopy, both the OLGA score and the OLGIM score were significantly lower than those before treatment.

[0041] Before taking the medicine, at the baseline, the OLGA and OLGIM stages were IV and IV respectively. The pathological histological results were as Figure 2 shown, which was moderate chronic atrophic gastritis with glandular intestinal metaplasia, partial disappearance of the proper glands, and a large number of lymphocytes infiltrated in the stroma. Among them, "the greater curvature of the gastric antrum" showed moderate chronic atrophic gastritis with intestinal metaplasia; "the lesser curvature of the gastric antrum" showed chronic mucosal inflammation with intestinal metaplasia, and no mucosal muscle was seen; "the gastric angle" showed moderate chronic atrophic gastritis with intestinal metaplasia and lymphoid follicle formation; "the greater curvature of the gastric body" showed chronic mucosal inflammation, and no mucosal muscle was seen; "the lesser curvature of the gastric body" showed severe chronic atrophic gastritis with intestinal metaplasia.

[0042] After taking the Chinese medicine prescription of Hesuo Tiaowei Powder for 6 months, the OLGA and OLGIM stages were reduced to I and I respectively. The pathological histological results were as Figure 3 shown, which was the improvement of chronic superficial gastritis. There were more proper glands in the mucosal layer, the glandular intestinal metaplasia was significantly reduced, the number of inflammatory cells in the stroma decreased, mild edema, and hyperplasia of thin-walled small blood vessels. Among them, "the greater curvature of the gastric antrum" showed chronic mucosal inflammation, and no mucosal muscle was seen; "the lesser curvature of the gastric antrum" showed mild chronic atrophic gastritis with intestinal metaplasia; "the gastric angle" showed chronic mucosal inflammation with intestinal metaplasia, and no mucosal muscle was seen; "the greater curvature of the gastric body" showed moderate chronic superficial gastritis; "the lesser curvature of the gastric body" showed mild chronic atrophic gastritis with intestinal metaplasia.

[0043] No obvious adverse reaction events occurred during the observation process.

Claims

1. A traditional Chinese medicine for treating chronic atrophic gastritis, characterized in that It is prepared from the following traditional Chinese medicine raw materials: Lotus leaf, Chinese sweetgum fruit, stir-fried Atractylodes macrocephala, roasted Astragalus membranaceus, Chinese yam, Lindera aggregata, Lysimachia christinae, calcined Armored Squama, dandelion Among them, the dosage of each medicine is within the dosage range specified in the Chinese Pharmacopoeia, and the drug composition can be increased or decreased within the above drug range.

2. The traditional Chinese medicine according to claim 1, wherein It is prepared from the following traditional Chinese medicine raw materials by weight: 12 g of lotus leaf, 9 g of Chinese sweetgum fruit, 15 g of stir-fried Atractylodes macrocephala, 15 g of roasted Astragalus membranaceus, 10 g of Chinese yam, 12 g of Lindera aggregata, 15 g of Lysimachia christinae, 12 g of calcined Armored Squama, 15 g of dandelion.

3. The traditional Chinese medicine according to claim 1 or 2, characterized in that The traditional Chinese medicine is a prescription prepared from lotus leaf, Chinese sweetgum fruit, stir-fried Atractylodes macrocephala, roasted Astragalus membranaceus, Chinese yam, Lindera aggregata, Lysimachia christinae, calcined Armored Squama, dandelion, and is used for treating chronic atrophic gastritis.

4. The traditional Chinese medicine according to claim 1 or 2, wherein The traditional Chinese medicine is a prescription prepared from lotus leaf, Chinese sweetgum fruit, stir-fried Atractylodes macrocephala, roasted Astragalus membranaceus, Chinese yam, Lindera aggregata, Lysimachia christinae, calcined Armored Squama, dandelion, and is used for treating epigastric pain of spleen deficiency and damp-heat type.

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