Traditional Chinese medicine composition for treating chronic atrophic gastritis and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating chronic atrophic gastritis. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 10 to 20 parts of radix codonopsis, 10 to 20 parts of rhizoma atractylodis macrocephalae, 10 to 15 parts of poria cocos, 10 to 12 parts of pericarpium citri reticulatae, 6 to 10 parts of rhizoma pinellinae praeparata, 10 to 12 parts of radix aucklandiae, 10 to 12 parts of rhizoma corydalis, 3 to 6 parts of radix notoginseng, 10 to 12 parts of fructus aurantii immaturus, 10 to 20 parts of radix ginseng rubra, 15 to 30 parts of herba hedyotidis diffusae, 15 to 30 parts of semen coicis, 10 to 15 parts of rhizoma curcumae, 10 to 20 parts of radix salviae miltiorrhizae, 10 to 20 parts of radix astragali seu hedysari and 3 to 6 parts of liquorice root. The invention further discloses a preparation method of the traditional Chinese medicine composition. The traditional Chinese medicine composition aims at chronic atrophic gastritis with pathological characteristics of gastric mucosa dysplasia and intestinal metaplasia, and is remarkable in curative effect and small in side effect through reasonable medicine compatibility.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine preparation, in particular to a traditional Chinese medicine composition for treating chronic atrophic gastritis with pathological characteristics of gastric mucosa heterotypic hyperplasia and intestinal epithelial metaplasia and a preparation method thereof. BACKGROUND

[0002] Chronic atrophic gastritis (CAG) is a chronic digestive system disease characterized by progressive atrophy of gastric mucosa epithelium and glands, reduction of gland number, and thinning of gastric mucosa with thickening of mucosal muscle layer. Intestinal metaplasia (IM), as a key pathological change of CAG, is considered as an important precancerous lesion of gastric cancer. Epidemiological data shows that the global incidence of this disease is on the rise.

[0003] In terms of treatment, modern medicine mainly adopts symptomatic treatment strategies such as acid suppressants (e.g. proton pump inhibitors), gastric mucosa protectants, prokinetics, and Helicobacter pylori (HP) eradication therapy. However, existing treatment methods are still difficult to achieve pathological disease progression blocking or histological reversal. It is worth noting that in recent years, traditional Chinese medicine has shown unique advantages in the field of intervention of precancerous lesions of gastric cancer. Multiple clinical studies have confirmed that it can effectively reverse precancerous lesions such as gastric mucosa heterotypic hyperplasia and intestinal epithelial metaplasia through multi-target and multi-pathway mechanisms.

[0004] After searching the patent database, it is found that: 1) Patent document CN202311716040.1 discloses a traditional Chinese medicine composition for treating chronic atrophic gastritis and its application, which is made from the following raw materials in parts by weight: Dangshen 8-15 parts, Baizhu 8-15 parts, Fuling 8-15 parts, Sanleng 8-12 parts, Wuzipiaoxie 25-35 parts, Banzhi 10-20 parts, Shanyao 25-35 parts, Shihu 8-15 parts, Fabanxia 6-10 parts, Chaihu 8-15 parts, Yujin 8-15 parts, Gancao 4-10 parts. The traditional Chinese medicine composition has a definite therapeutic effect on chronic atrophic gastritis, providing a new drug option for treating chronic atrophic gastritis. The traditional Chinese medicine composition is a pure traditional Chinese medicine prescription with good clinical efficacy, small side effects, and is suitable for clinical popularization and application. 2) Patent document CN202110892098.6 discloses a traditional Chinese medicine composition for treating chronic atrophic gastritis, a preparation method and application, which is made from the following raw materials in parts by weight: Shudihuang 14-16 parts, Haipiaoxie 18-22 parts, Shashen 7-11 parts, Maidong 14-16 parts, Shanzhu 8-10 parts, Baishao 14-16 parts, Dangshen 7-11 parts, Baizhu 10-14 parts, Huomaren 28-32 parts, Baizi 18-22 parts, Suanzaoren 14-16 parts, Yuzhu 8-10 parts, Zhigancao 4-8 parts, Sanqi 7-11 parts, Guiban 8-12 parts, and Zhimu 4-6 parts. The application also discloses a preparation method and application of the traditional Chinese medicine composition for treating chronic atrophic gastritis. The traditional Chinese medicine composition for treating chronic atrophic gastritis has the effects of invigorating the spleen and tonifying qi, removing blood stasis and detoxifying, nourishing the stomach and the stomach, and can be used for treating atrophic gastritis.

[0005] However, the existing traditional Chinese medicine composition technical solution does not target patients with chronic atrophic gastritis with gastric mucosa heterotypic hyperplasia and intestinal epithelial metaplasia pathological characteristics. The existing technology targets all patients with chronic atrophic gastritis, who may have various clinical symptoms.

[0006] Therefore, for patients with chronic atrophic gastritis with gastric mucosa heterotypic hyperplasia and intestinal epithelial metaplasia pathological characteristics, the symptomatic treatment effect will be more definite; the traditional Chinese medicine formula design of the technical solution will also be more targeted. It has important clinical significance to develop a safe and effective traditional Chinese medicine composition for treating patients with chronic atrophic gastritis with gastric mucosa heterotypic hyperplasia and intestinal epithelial metaplasia pathological characteristics. SUMMARY

[0007] In order to solve the technical problems existing in the prior art, the present application provides a traditional Chinese medicine composition for treating chronic atrophic gastritis with gastric mucosa heterotypic hyperplasia and intestinal epithelial metaplasia pathological characteristics and a preparation method thereof.

[0008] The application provides a traditional Chinese medicine composition for treating chronic atrophic gastritis, which is composed of the following raw materials in parts by weight: Radix Codonopsis 10-20 parts, Rhizoma Atractylodis Macrocephalae 10-20 parts, Poria 10-15 parts, Pericarpium Citri Reticulatae 10-12 parts, Rhizoma Pinelliae Praeparatum 6-10 parts, Radix Aucklandiae 10-12 parts, Rhizoma Corydalis 10-12 parts, Panax Notoginseng 3-6 parts, Fructus Aurantii Immaturus 10-12 parts, Red Ginseng 10-20 parts, Oldenlandia 15-30 parts, Coix 15-30 parts, Curcuma 10-15 parts, Salvia Miltiorrhiza 10-20 parts, Astragalus 10-20 parts, and Glycyrrhiza 3-6 parts.

[0009] In a preferred embodiment of the traditional Chinese medicine composition for treating chronic atrophic gastritis provided by the application, the chronic atrophic gastritis is chronic atrophic gastritis with gastric mucosa heterotypic hyperplasia and intestinal epithelial metaplasia pathological characteristics.

[0010] In a preferred embodiment of the traditional Chinese medicine composition for treating chronic atrophic gastritis provided by the application, the parts by weight of the raw materials are as follows: Radix Codonopsis 15 parts, Rhizoma Atractylodis Macrocephalae 15 parts, Poria 12 parts, Pericarpium Citri Reticulatae 10 parts, Rhizoma Pinelliae Praeparatum 8 parts, Radix Aucklandiae 10 parts, Rhizoma Corydalis 10 parts, Panax Notoginseng 5 parts, Fructus Aurantii Immaturus 10 parts, Red Ginseng 15 parts, Oldenlandia 20 parts, Coix 20 parts, Curcuma 12 parts, Salvia Miltiorrhiza 15 parts, Astragalus 15 parts, and Glycyrrhiza 5 parts.

[0011] The application further provides a preparation method of the traditional Chinese medicine composition for treating chronic atrophic gastritis, which comprises the following steps: Step one, raw material pretreatment: The raw materials are weighed according to the weight parts, cleaned and impurities are removed, and then dried for standby use; wherein, the Red Ginseng and Panax Notoginseng are crushed into fine powder (passing through an 80-100 mesh sieve), and the rest of the raw materials are respectively broken or sliced appropriately to facilitate the extraction of effective components; Step two, decoction and extraction: Radix Codonopsis, Rhizoma Atractylodis Macrocephalae, Poria, Pericarpium Citri Reticulatae, Rhizoma Pinelliae Praeparatum, Radix Aucklandiae, Rhizoma Corydalis, Fructus Aurantii Immaturus, Oldenlandia, Coix, Curcuma, Salvia Miltiorrhiza, Astragalus, and Glycyrrhiza are soaked in water for 30-60 minutes, and the water amount is 8-12 times of the total weight of the raw materials; Decoction is heated twice, the first time for 1-2 hours and the second time for 0.5-1 hour, the decoction of the two times is combined, filtered, and the extraction liquid is obtained; The extraction liquid is concentrated under reduced pressure to a thick paste with a relative density of 1.10-1.20 (measured at 60℃); Step three, mixing and drying: The Red Ginseng powder and Panax Notoginseng powder are mixed uniformly with the above thick paste; The spray drying or vacuum drying method is adopted to prepare dry extract powder, and the water content is controlled to be less than or equal to 5%; Step four, preparation of preparation: Mix the dry extract powder with a proper amount of pharmaceutical excipients (such as starch, microcrystalline cellulose, etc.), and according to the needs, make granules, capsules, tablets or pills.

[0012] In the preferred embodiment of the preparation method of the traditional Chinese medicine composition for treating chronic atrophic gastritis provided by the application, the raw materials in step one need to be accurately weighed to ensure the exertion of the drug efficacy, i.e., the weight parts of the raw materials are as follows: radix codonopsis 15 parts, atractylodes 15 parts, poria cocos 12 parts, dried tangerine or orange peel 10 parts, radix pinelliae 8 parts, saussurea 10 parts, corydalis 10 parts, panax notoginseng 5 parts, immature bitter orange fruit 10 parts, red ginseng 15 parts, oldenlandia 20 parts, coix seed 20 parts, curcuma zedoary 12 parts, salvia miltiorrhiza 15 parts, radix astragali 15 parts, and liquorice 5 parts.

[0013] In the preferred embodiment of the preparation method of the traditional Chinese medicine composition for treating chronic atrophic gastritis provided by the application, the extract liquid in step two can be further purified by using macroporous adsorption resin or alcohol precipitation method to remove impurities and improve the content of effective components.

[0014] Compared with the prior art, the application has the following beneficial effects: (1) Multi-target synergistic effect, comprehensive improvement of pathological state of gastric mucosa The traditional Chinese medicine composition tonifies qi and invigorates the spleen with radix codonopsis, radix astragali and red ginseng, invigorates the spleen and removes dampness with atractylodes and poria cocos, removes stagnation with dried tangerine or orange peel, saussurea, and immature bitter orange fruit, reduces adverse flow and regulates the stomach with radix pinelliae, promotes blood circulation and removes blood stasis with corydalis, panax notoginseng, salvia miltiorrhiza, curcuma zedoary, oldenlandia, coix seed, and liquorice. The combination of the drugs can regulate the function of the spleen and stomach, improve the microcirculation of the gastric mucosa, and promote the repair of the glands, thereby effectively reversing the atrophy of the gastric mucosa and the intestinal epithelial metaplasia, and blocking the progression of precancerous lesions of gastric cancer.

[0015] (2) Significant inhibition of inflammatory response and reduction of gastric mucosal damage Oldenlandia, salvia miltiorrhiza, and curcuma zedoary in the traditional Chinese medicine composition have anti-inflammatory and antioxidant effects, can reduce the expression of inflammatory factors (such as TNF-α, IL-6, and NF-κB) of the gastric mucosa, reduce the oxidative stress damage of the gastric mucosa, and thereby delay or even reverse the pathological process of chronic atrophic gastritis.

[0016] (3) Promotion of gastric mucosal repair and regeneration The components such as panax notoginseng, salvia miltiorrhiza, and radix astragali in the traditional Chinese medicine composition can enhance the blood supply of the gastric mucosa, promote the proliferation of epithelial cells, improve the barrier function of the gastric mucosa, accelerate the recovery of atrophic glands, and reduce the thinning and fibrosis of the gastric mucosa.

[0017] (4) Regulation of gastrointestinal motility and improvement of clinical symptoms The costus root, immature bitter orange, corydalis yanhusuo and other herbs in this Chinese medicine composition have the effects of regulating qi and relieving pain, and promoting gastrointestinal motility. They can effectively relieve the symptoms of abdominal distension, abdominal pain, belching, indigestion and the like in patients with chronic atrophic gastritis, and improve the quality of life of patients.

[0018] (5) Inhibit Helicobacter pylori (Hp) infection and reduce the risk of cancer The herbs in the traditional Chinese medicine composition of this scheme, such as Hedyotis diffusa, Curcuma zedoaria, and Coptis chinensis (if used in combination), have antibacterial activity, can assist in inhibiting the growth of Hp, and reduce the risk of Hp-related gastritis canceration.

[0019] (6) Safe and effective, reducing adverse reactions to Western medicine Compared with the side effects such as hypochlorhydria and intestinal flora imbalance that may be caused by long-term use of proton pump inhibitors (PPIs), this Chinese medicine composition is based on holistic conditioning, has fewer adverse reactions, is suitable for long-term use, and improves patient compliance. DETAILED DESCRIPTION

[0020] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0021] Example 1: Preparation of Chinese medicine composition

[0022] 1) The mechanism of action of the Chinese medicine composition: 1 / Analysis of medicinal taste: Nature and flavor combination for chronic atrophic gastritis (with gastric mucosal dysplasia and intestinal metaplasia) This Chinese medicine composition targets the core pathogenesis of chronic atrophic gastritis (CAG) accompanied by gastric mucosal dysplasia and intestinal metaplasia (spleen and stomach deficiency, qi stagnation and blood stasis, and internal accumulation of dampness and heat), and achieves multi-target synergistic treatment of strengthening the spleen and replenishing qi, promoting blood circulation and removing blood stasis, clearing away heat and removing dampness, and regulating qi and relieving pain through the combination of properties and flavors.

[0023] This Chinese medicine composition is composed of 16 Chinese herbs, covering four categories: tonifying qi and strengthening the spleen, promoting blood circulation and removing blood stasis, clearing away heat and dampness, and regulating qi and relieving pain: Qi-tonifying and spleen-strengthening herbs (6 ingredients): Codonopsis pilosula, red ginseng, astragalus, white atractylodes, poria, and liquorice; Blood-activating and stasis-removing herbs (4 ingredients): Panax notoginseng, Salvia miltiorrhiza, Curcuma zedoaria, and Corydalis yanhusuo; Heat-clearing and dampness-removing herbs (3 ingredients): Hedyotis diffusa, Coix seed, and Pinellia ternata; Qi-regulating and analgesic drugs (3 ingredients): dried tangerine peel, costus root, and immature bitter orange.

[0024] a. Codonopsis pilosula (primary herb) Flavor: sweet, flat; spleen, lung.

[0025] Effect: greatly replenish the spleen and stomach, enhance the repair capacity of the gastric mucosa; improve the body's immunity, inhibit the progression of gastric mucosal atrophy.

[0026] Compatibility: For the core pathogenesis of spleen and stomach weakness, it is the basis of the whole prescription for tonifying qi and invigorating the spleen.

[0027] b. Red ginseng (monarch drug) Flavor: sweet, bitter, warm; spleen, lung, heart.

[0028] Effect: warm and tonify the primordial qi, promote the regeneration of gastric mucosal glands; enhance the qi-tonifying effect of radix codonopsis, and improve insufficient gastric motility.

[0029] Compatibility: synergize with radix codonopsis to strengthen the spleen and invigorate qi.

[0030] c. Huangqi (monarch drug) Flavor: sweet, slightly warm; spleen, lung.

[0031] Effect: tonifying qi and raising yang, improving gastric mucosal microcirculation; promoting ulcer healing.

[0032] Compatibility: auxiliary monarch drug to enhance the qi-tonifying effect, and also can promote blood circulation and promote tissue regeneration.

[0033] d. Baizhu (monarch drug) Flavor: bitter, sweet, warm; spleen, stomach.

[0034] Effect: invigorating the spleen and drying dampness, improving gastric mucosal edema; enhancing gastrointestinal peristalsis and relieving abdominal distension.

[0035] Compatibility: combined with Fuling to strengthen the spleen and dry dampness.

[0036] e. Fuling (monarch drug) Flavor: sweet, mild, flat; heart, lung, spleen, kidney.

[0037] Effect: diuresis and dampness, invigorating the spleen and calming the heart; improve the edema state of the gastric mucosa and regulate gastrointestinal function.

[0038] Compatibility: synergize with Baizhu to enhance the spleen and dry dampness, while soothing the mind and helping sleep.

[0039] f. Sanqi (ministerial drug) Flavor: sweet, bitter, warm; liver, stomach.

[0040] Effect: promoting blood circulation and stopping bleeding, improving gastric mucosal microcirculation; inhibiting fibrosis and reversing intestinal epithelial metaplasia.

[0041] Compatibility: for the blood stasis pathogenesis, prevent further atrophy of the gastric mucosa.

[0042] g. Salvia miltiorrhiza (ministerial medicine) Nature and taste: bitter, slightly cold; return to the heart, liver meridian.

[0043] Effect: Activating blood and removing blood stasis, unblocking channels and relieving pain; improving microcirculation, resisting oxidative damage.

[0044] Compatibility: Synergistic effect with Sanqi to enhance blood circulation, protect gastric mucosa.

[0045] h. Rhizoma Curcumae (ministerial medicine) Nature and taste: pungent, bitter, warm; return to the liver, spleen meridian.

[0046] Effect: Breaking blood and promoting qi, eliminating accumulation and relieving pain; improving microcirculation, inhibiting tissue hyperplasia.

[0047] Compatibility: Synergistic effect with Danshen to enhance blood circulation and remove blood stasis, reverse intestinal epithelial metaplasia.

[0048] i. Oldenlandia diffusa (ministerial medicine) Nature and taste: bitter, sweet, cold; return to the stomach, large intestine, small intestine meridian.

[0049] Effect: Clearing heat and resolving toxins, inhibiting Helicobacter pylori (Hp); anti-inflammatory and antioxidant, reducing gastric mucosal damage.

[0050] Compatibility: Aimed at internal damp-heat to prevent canceration.

[0051] j. Coix lachryma-jobi (ministerial medicine) Nature and taste: sweet, light, cool; return to the spleen, stomach, lung meridian.

[0052] Effect: Diuresis and dampness, spleen and diarrhea; anti-inflammatory and antioxidant, regulating immunity.

[0053] Compatibility: Synergistic effect with Oldenlandia diffusa to enhance heat-clearing and dampness-removing effect.

[0054] k. Pericarpium Citri Reticulatae (adjuvant) Nature and taste: bitter, pungent, warm; return to the spleen, lung meridian.

[0055] Effect: Regulating qi and invigorating the spleen, drying dampness and reducing sputum; promoting gastric juice secretion, improving digestive function.

[0056] Compatibility: Synergistic effect with Aucklandia to enhance qi-regulating effect, prevent dampness and hinder the stomach.

[0057] l. Aucklandia (adjuvant) Nature and taste: pungent, bitter, warm; return to the spleen, stomach, large intestine meridian.

[0058] Effect: Qi-regulating and pain-relieving, spleen-strengthening and food-digesting; regulating gastrointestinal peristalsis, relieving distension and pain.

[0059] Compatibility: Synergistic effect with Fructus Aurantii to enhance qi-regulating effect and improve gastric motility disorders.

[0060] m. Citrus aurantium (adjuvant) Nature and flavor: bitter, pungent, slightly cold; returns to the spleen and stomach meridians.

[0061] Effect: Breaks qi and eliminates accumulation, relieves epigastric fullness; leads the drug downward, enhancing the targeting nature of the overall prescription.

[0062] Compatibility significance: Harmonizes various drugs to avoid stagnation of tonifying drugs.

[0063] n. Pinellia ternata (adjuvant) Nature and flavor: pungent, warm; returns to the spleen, stomach, and lung meridians.

[0064] Effect: Dries dampness and resolves phlegm, descending adverse qi and stopping vomiting; inhibits excessive gastric acid secretion and protects the gastric mucosa.

[0065] Compatibility significance: Targets the pathogenesis of phlegm and dampness obstruction, improving symptoms of nausea and vomiting.

[0066] o. Corydalis (adjuvant) Nature and flavor: pungent and bitter, warm; returns to the liver and spleen meridians.

[0067] Effect: Activates blood and moves qi, stopping pain; inhibits gastric acid secretion and protects the gastric mucosa.

[0068] Compatibility significance: Synergizes with Sanqi to enhance blood-activating and pain-stopping effects, targeting stomach pain.

[0069] p. Glycyrrhiza (adjuvant) Nature and flavor: sweet, neutral; returns to the heart, lung, spleen, and stomach meridians.

[0070] Effect: Tonifies the spleen and replenishes qi, clearing heat and resolving toxins; harmonizes various drugs, alleviating acute and relieving pain.

[0071] Compatibility significance: Harmonizes the overall prescription, enhancing the protective effect on the gastric mucosa.

[0072] 2 / Prescription structure: hierarchical division based on the "monarch - minister - adjuvant - assistant" principle a. Monarch drug (core therapeutic effect) Dangshen, Hongshen, and Huangqi: greatly tonify the spleen and stomach qi, enhance the body's immune function, and promote gastric mucosa repair.

[0073] Baizhu and Fuling: tonify the spleen and eliminate dampness, restore the spleen and stomach transportation function, and improve gastric mucosa edema and atrophy.

[0074] b. Minister drug (auxiliary monarch, enhance efficacy) Sanqi, Danshen, and E Zhi: activate blood and resolve stasis, improve gastric mucosa microcirculation, inhibit fibrosis, and reverse intestinal epithelial metaplasia.

[0075] Baihua Sheche and Yiyiren: clear heat and resolve toxins, remove dampness and turbidity, and inhibit Helicobacter pylori (Hp) and inflammatory reactions.

[0076] c. Adjuvant (synergistic conditioning, reduce symptoms) Chenpi, Muxiang, Jisheng: regulating qi and relieving distension, promoting gastrointestinal peristalsis, relieving abdominal distension, belching and other symptoms.

[0077] Fabanxia: descending adverse stomach, stopping vomiting and reducing phlegm, targeting nausea, acid reflux and other stomach qi uprush symptoms.

[0078] Yansu: regulating qi and relieving pain, specifically treating stomach pain.

[0079] d. Messenger (harmonize drug properties, lead to the messenger) Gancao: harmonizing various drugs, relieving pain, protecting gastric mucosa.

[0080] 3 / Compatibility characteristics and innovation points 1) Compatibility characteristics: a. Supplement and reduce, treat both symptoms and root causes Supplementing qi (Dangshen, Hongshen) and promoting blood circulation (Sanqi, Danshen) together, both supporting the body and removing blood stasis; Spleen-boosting herbs (Baizhu, Fuling) and qi-regulating herbs (Jisheng, Muxiang) are combined to supplement without stagnation.

[0081] b. Cold and warm together, dynamic balance Hongshen (warm and tonifying) and Baishuaxiecao (cold and cooling) are combined to avoid damaging yin by warm and dry or damaging stomach by cold and cooling.

[0082] c. Regulating qi and blood, considering inflammation and atrophy Blood-activating herbs (Ezhu, Sanqi) improve microcirculation, and heat-clearing herbs (Baishuaxiecao) resist inflammation, blocking the "atrophy-hyperplasia-carcinoma" process.

[0083] 2) Innovation points: a. Multiple targets reverse precancerous lesions of gastric cancer On the basis of traditional spleen-boosting formula, Ezhu and Baishuaxiecao are added to specifically intervene in intestinal epithelial metaplasia.

[0084] b. Mechanism of traditional Chinese and Western medicine combination is clear Danshengtong (Danshen) and Sanqizhaosan (Sanqi) can inhibit the NF-κB pathway and reduce gastric mucosal inflammation.

[0085] c. Optimize the dosage ratio Baishuaxiecao (15-30 parts) and Yiyiren (15-30 parts) are used together to enhance the anti-Hp effect; Gancao (3-6 parts) is used in low dose to harmonize drug properties without dampness.

[0086] d. Summary: The traditional Chinese medicine composition breaks through the simple symptomatic treatment mode through the synergistic effect of "invigorating the spleen, activating blood, clearing heat and regulating qi", and provides an innovative scheme of pathological reversal and symptom improvement for chronic atrophic gastritis and precancerous lesions.

[0087] 2) The preparation process of the traditional Chinese medicine composition: Step one, raw material pretreatment:

[0088] 1) Wash the 16 kinds of medicinal materials of dangshen, baizhu, fuling, chenpi, fabanxia, muxiang, yanhuosuo, sanqi, zhishi, red ginseng, baihuasheshecao, yiyiren, e zhu, danshen, huangqi and gancao with clean water, and remove impurities such as mud; 2) Dry the washed medicinal materials in a cool and ventilated place or low-temperature drying (temperature not more than 50℃); 3) Accurately weigh each medicinal material according to the formula, and separately crush red ginseng and sanqi to 80-100 mesh for use; 4) Prepare the decoction equipment, concentration equipment and preparation mold, etc.

[0089] Specifically, the raw material formula needs to be accurately weighed to ensure the play of the medicinal effect, that is, the weight parts of the raw materials are: dangshen 10-20g, baizhu 10-20g, fuling 10-15g, chenpi 10-12g, fabanxia 6-10g, muxiang 10-12g, yanhuosuo 10-12g, sanqi 3-6g, zhishi 10-12g, red ginseng 10-20g, baihuasheshecao 15-30g, yiyiren 15-30g, e zhu 10-15g, danshen 10-20g, huangqi 10-20g, and gancao 3-6g.

[0090] The weight parts of the three raw materials are preferably matched as follows: 1) Dangshen 10g, baizhu 10g, fuling 10g, chenpi 10g, fabanxia 6g, muxiang 10g, yanhuosuo 10g, sanqi 3g, zhishi 10g, red ginseng 10g, baihuasheshecao 15g, yiyiren 15g, e zhu 10g, danshen 10g, huangqi 10g, and gancao 3g.

[0091] 2) Dangshen 15g, baizhu 15g, fuling 12g, chenpi 10g, fabanxia 8g, muxiang 10g, yanhuosuo 10g, sanqi 5g, zhishi 10g, red ginseng 15g, baihuasheshecao 20g, yiyiren 20g, e zhu 12g, danshen 15g, huangqi 15g, and gancao 5g (preferred embodiment).

[0092] 3) Dangshen 20g, Baizhu 20g, Fuling 15g, Chenpi 12g, Fabanxia 10g, Muxiang 12g, Yuhuoso 12g, Sanqi 6g, Jizhi 12g, Hongshen 20g, Baihuasheshecao 30g, Yiyiren 30g, E'zhu 15g, Danshen 20g, Huangqi 20g, Gancao 6g.

[0093] Raw material handling considerations: 1) The medicinal materials should meet the standards of Chinese Pharmacopoeia, and ensure no mildew, insect damage; 2) Medicinal materials containing volatile oil components such as Muxiang and Chenpi should be stored separately; 3) Precious medicinal materials such as Hongshen and Sanqi should be identified for authenticity; 4) The weighing error should be controlled within ±2%.

[0094] Step two, decoction and extraction:

[0095] 1) Dangshen, Baizhu, Fuling, Chenpi, Fabanxia, Muxiang, Yuhuoso, Jizhi, Baihuasheshecao, Yiyiren, E'zhu, Danshen, Huangqi, and Gancao are soaked in water for 30-60 minutes, and the amount of water added is 8-12 times the total weight of the medicinal materials; 2) Heat and decoct twice, the first time for 1-2 hours and the second time for 0.5-1 hour, combine the two decoctions, filter, and obtain the extract; 3) Reduce the pressure and concentrate the extract to a thick paste with a relative density of 1.10-1.20 (measured at 60°C).

[0096] Specifically: 1) Mix the 14 medicinal materials except Hongshen and Sanqi, and soak them in 8 times the amount of water for 40 minutes; 2) First decoction for 1.5 hours, filter and collect the medicinal liquid; 3) Add 6 times the amount of water to the medicinal residue, and second decoction for 1 hour, filter; 4) Combine the two decoctions and filter through a 200-mesh sieve; 5) Reduce the pressure and concentrate the filtrate to a thick paste with a relative density of 1.15 at 60°C.

[0097] Preparation process considerations: 1) Maintain a slight boiling state during decoction to avoid vigorous boiling; 2) Add medicinal materials containing volatile oil such as Muxiang 15 minutes before the end of decoction; 3) Control the concentration temperature at 60°C or below; 4) Control the water content of the thick paste to 25%-30%.

[0098] Step three, mixing and drying:

[0099] 1) Mix the Hongshen powder, Sanqi powder, and the above thick paste evenly; 2) Spray-drying or vacuum-drying method is used to make dry extract powder, with moisture content controlled at ≤5%.

[0100] Step four, preparation of the preparation:

[0101] The dry extract powder is mixed with appropriate amount of pharmaceutical excipients (such as starch, microcrystalline cellulose, etc.), and granules, capsules, tablets or pills are prepared according to the needs.

[0102] Specifically, an appropriate amount of starch dextrin (20% of the weight of the extract) is added as an excipient. The dry extract powder is sieved through an 80-mesh sieve and then loaded into capsules (0.3 g per capsule) or compressed into tablets (0.5 g per tablet).

[0103] Quality control considerations: 1) The dry extract powder needs to be assayed (tanshinone II A ≥ 0.5 mg / g); 2) The capsule loading difference is controlled within ±7%; 3) The tablet hardness is controlled at 4-6 kg / cm²; 4) The finished product needs to be subjected to microbial limit test.

[0104] 3) Usage method and precautions of traditional Chinese medicine composition: 1 / Usage method: 1) Oral administration, 3 times a day; 2) Capsules: 4 capsules each time, taken with warm water 30 minutes before meals; tablets: 3 tablets each time, taken with warm water 30 minutes before meals; 3) Continuous use for 4 weeks as a course of treatment; 4) Continuous use for 2-3 courses is required.

[0105] 2 / Precautions: 1) Avoid eating cold, greasy, spicy and irritating foods during medication; 2) Avoid taking with strong tea and coffee; 3) Pregnant women should use with caution, and lactating women are prohibited; 4) If stomach discomfort occurs after taking the medicine, it can be taken after meals; 5) Regular re-examination of gastroscope should be performed during treatment (every 3 months); 6) Those who are allergic to any of the ingredients are prohibited.

[0106] 3 / Special population medication: 1) Use with caution in patients with abnormal liver function; 2) Those with allergic constitution are advised to do skin test first; 3) The safety of children has not been established, and use is not recommended.

[0107] Example 2: Clinical effect of traditional Chinese medicine composition

[0108] I. Purpose of the test The purpose of this clinical trial is to scientifically evaluate the effectiveness and safety of the traditional Chinese medicine composition in treating chronic atrophic gastritis (with gastric mucosal atrophy and intestinal metaplasia). Through a multi-center, randomized, double-blind, placebo-controlled study design, the focus is on verifying its effectiveness in reversing gastric mucosal pathological changes (including improvement of atrophy degree and reversal rate of intestinal metaplasia), relieving clinical symptoms (such as upper abdominal pain, abdominal distension, etc.), and improving patients' quality of life. At the same time, adverse drug reactions are observed to provide high-level evidence-based medical evidence for clinical application and explore its possible mechanism of action.

[0109] II. Test design 1. Grouping method: Randomized controlled trial design. 265 subjects who meet the diagnostic criteria from Hunan University of Chinese Medicine First Affiliated Hospital, Hunan University of Chinese Medicine Second Affiliated Hospital, and Hunan University of Chinese Medicine Affiliated Changde Hospital were randomly divided into test and control groups by random number table method, with 135 in the test group and 130 in the control group. The grouping process was handled by a dedicated person to ensure the randomness and confidentiality of the grouping, and after grouping, both patients and researchers were treated with blind method to reduce the influence of subjective factors on the test results.

[0110] Subject selection criteria: A. Inclusion criteria: 1) Age 18-70 years old; 2) Diagnosed by gastroscope and pathology as chronic atrophic gastritis with intestinal metaplasia; 3) H. pylori negative or eradicated; 4) Spleen and stomach deficiency syndrome in TCM differentiation.

[0111] B. Exclusion criteria: 1) Combined with serious organic diseases such as peptic ulcer, gastric cancer, etc.; 2) Pregnant or lactating women; 3) Allergic to test drug ingredients.

[0112] 2. Treatment plan: Test group: This traditional Chinese medicine composition tablet treatment (3 times a day, 3 tablets each time, taken with warm water 30 minutes before meals); Control group: placebo treatment with the same appearance (3 times a day, 3 tablets each time, taken with warm water 30 minutes before meals).

[0113] Both groups are treated for 4 weeks as a course of treatment, with a total of 6 courses of continuous treatment. During the treatment period, patients are required to maintain normal daily routines and eating habits, avoid excessive fatigue and mental stimulation.

[0114] III. Observation indicators 1. Primary endpoint: 1) Gastric mucosa histopathological improvement (Sydney system score); 2) Reversal rate of intestinal epithelial metaplasia.

[0115] 2. Secondary endpoints: 1) Clinical symptom score (abdominal distension, pain, etc. VAS score); 2) Pepsinogen I / II ratio; 3) Quality of life scale (SF-36).

[0116] 3. Safety indicators: 1) Liver and kidney function, blood routine; 2) Adverse event records.

[0117] Four, statistical analysis 1. Data set definition: 1) FAS (full analysis set): all randomized subjects; 2) PPS (per-protocol set): subjects who completed all treatment; 3) SS (safety set): subjects who received at least one treatment.

[0118] 2. Statistical methods: 1) Measurement data: t-test or Mann-Whitney U test; 2) Count data: chi-square test or Fisher's exact test; 3) Rank data: Wilcoxon rank-sum test; 4) Repeated measurement data: mixed effect model; 5) Survival analysis: Kaplan-Meier method; all tests two-sided α = 0.05.

[0119] 3. Analysis of trial results: Evaluation index Test group (n=135) Control group (n=130) Statistical value P value Pathological improvement rate 68.9% 42.3% χ²=19.32 <0.001 Intestinal metaplasia reversal rate 52.6% 28.5% OR=2.81 (1.72-4.59) <0.001 Symptom relief rate 82.2% 58.5% RR=1.41 (1.19-1.66) 0.002 PGⅠ / Ⅱ ratio 5.2±1.8 3.6±1.5 t=7.65 <0.001 Adverse events 8.1% 6.9% χ²=0.15 0.698 a. Survival analysis results: Median time of pathological improvement: 18 weeks in the test group vs. not reached in the control group (Log-rank χ²=24.17, P<0.001).

[0120] b. Multivariate analysis: This traditional Chinese medicine treatment is an independent predictor of pathological improvement (OR = 3.12, 95% CI: 1.85-5.26) Five, trial conclusion In this trial, the Chinese medicine composition showed significant efficacy and good safety in treating chronic atrophic gastritis (with gastric mucosa metaplasia and intestinal metaplasia). The main results showed that the treatment group was significantly better than the control group in terms of gastric mucosa pathological improvement rate (68.9% vs 42.3%, P<0.001) and intestinal metaplasia reversal rate (52.6% vs 28.5%, P<0.001); the clinical symptom remission rate (82.2% vs 58.5%, P=0.002) and life quality score improvement (SF-36 total score increased by 15.6±4.2 vs 8.3±3.7, P<0.001) were also significantly better than the placebo group. Safety analysis showed that there was no statistical difference in the incidence of adverse events between the two groups (8.1% vs 6.9%, P=0.698), and both were mild adverse reactions. Based on the above results, the Chinese medicine composition can effectively reverse the pathological changes of chronic atrophic gastritis, improve clinical symptoms, and has good safety, providing a new effective choice for the clinical treatment of precancerous lesions of gastric cancer.

[0121] Finally, it should be noted that: the above only for the preferred embodiments of the present application, and not for the limitation of the present application, although the foregoing detailed description of the present application is made with reference to the foregoing embodiments, for those skilled in the art, it still can be modified, or part of the technical features of the equivalent replacement, within the spirit and principles of the present application, any modification, equivalent replacement, improvement, etc., should be included in the scope of protection of the present application.

Claims

1. A Chinese medicine composition for treating chronic atrophic gastritis, characterized in that: The invention is composed of the following raw materials in parts by weight: 10-20 parts of Codonopsis pilosula, 10-20 parts of Atractylodes macrocephala, 10-15 parts of Poria cocos, 10-12 parts of dried tangerine peel, 6-10 parts of Pinellia ternata, 10-12 parts of costus root, 10-12 parts of Corydalis yanhusuo, 3-6 parts of Panax notoginseng, 10-12 parts of Citrus aurantium, 10-20 parts of red ginseng, 15-30 parts of Hedyotis diffusa, 15-30 parts of Coix seed, 10-15 parts of Curcuma zedoaria, 10-20 parts of Salvia miltiorrhiza, 10-20 parts of Astragalus membranaceus, and 3-6 parts of liquorice.

2. The Chinese medicine composition for treating chronic atrophic gastritis according to claim 1, characterized in that The chronic atrophic gastritis is a chronic atrophic gastritis with pathological characteristics of gastric mucosal dysplasia and intestinal metaplasia.

3. The Chinese medicine composition for treating chronic atrophic gastritis according to claim 2, characterized in that: The weight proportions of the raw materials are as follows: 15 parts of Codonopsis pilosula, 15 parts of Atractylodes macrocephala, 12 parts of Poria cocos, 10 parts of dried tangerine peel, 8 parts of Pinellia ternata, 10 parts of Aucklandia lappa, 10 parts of Corydalis yanhusuo, 5 parts of Panax notoginseng, 10 parts of Citrus aurantium, 15 parts of red ginseng, 20 parts of Hedyotis diffusa, 20 parts of Coix seed, 12 parts of Curcuma zedoaria, 15 parts of Salvia miltiorrhiza, 15 parts of Astragalus membranaceus, and 5 parts of Licorice.

4. A method for preparing a traditional Chinese medicine composition for treating chronic atrophic gastritis, characterized in that: The following steps are involved: Step 1: Raw material pretreatment: Weigh each medicinal material according to the weight portion, clean and remove impurities, and dry it for later use; among them, red ginseng and Panax notoginseng need to be crushed into fine powder (pass through an 80-100 mesh sieve), and the remaining medicinal materials are appropriately crushed or sliced ​​to facilitate the decoction of the active ingredients; Step 2: Decoction and extraction: Soak Codonopsis pilosula, Atractylodes macrocephala, Poria cocos, Tangerine peel, Pinellia ternata, Aucklandia lappa, Corydalis yanhusuo, Citrus aurantium, Hedyotis diffusa, Coix seed, Curcuma zedoaria, Salvia miltiorrhiza, Astragalus membranaceus, and Licorice root in water for 30-60 minutes, with the amount of water added being 8-12 times the total weight of the medicinal materials; Heat and decoct twice, the first decoction is 1-2 hours, the second decoction is 0.5-1 hour, the two decoctions are combined, filtered, and an extract is obtained; The extract is concentrated under reduced pressure to a thick paste having a relative density of 1.10-1.20 (measured at 60°C); Step 3: Mixing and drying: Mix red ginseng powder, Panax notoginseng powder and the above thick paste evenly; Use spray drying or vacuum drying to make dry extract powder, and control the moisture content to ≤5%; Step 4: Preparation of preparation: The dry extract powder is mixed with an appropriate amount of pharmaceutical excipients (such as starch, microcrystalline cellulose, etc.) and made into granules, capsules, tablets or pills as needed.

5. The method for preparing the Chinese medicine composition for treating chronic atrophic gastritis according to claim 4, wherein: The raw material formula in the step 1 needs to be accurately weighed to ensure the efficacy of the medicine, that is, the weight parts of the raw materials are: 15 parts of Codonopsis pilosula, 15 parts of Atractylodes macrocephala, 12 parts of Poria cocos, 10 parts of dried tangerine peel, 8 parts of Pinellia ternata, 10 parts of costus root, 10 parts of Corydalis yanhusuo, 5 parts of Panax notoginseng, 10 parts of Citrus aurantium, 15 parts of red ginseng, 20 parts of Hedyotis diffusa, 20 parts of Coix seed, 12 parts of Curcuma zedoaria, 15 parts of Salvia miltiorrhiza, 15 parts of Astragalus, and 5 parts of Licorice.

6. The method for preparing the Chinese medicine composition for treating chronic atrophic gastritis according to claim 5, characterized in that: The extract in step 2 can be further purified by using a macroporous adsorption resin or an alcohol precipitation method to remove impurities and increase the content of effective ingredients.