A pharmaceutical composition for treating chronic atrophic gastritis, and its preparation method and use

Abstract

The invention relates to a Chinese medicine composition, and discloses a medicine composition for treating chronic atrophic gastritis, a preparation method thereof and a use thereof. The medicine composition is prepared from effective ingredients and pharmaceutically acceptable auxiliary materials, wherein the effective ingredients are prepared from raw materials in the following weight ratio: 4-8g of red ginseng, 12-18g of white atractylodes, 4-8g of notoginseng, 4-6g of angelica, 8-12g of curcuma, 12-18g of coix seed, 12-18g of fritillaria thunbergii, 8-12g of dendrobium, 12-18g of falanghai, and 8-12g of salacia. Red ginseng and notoginseng are extracted by ethanol refluxing to obtain red ginseng and notoginseng extracts; red ginseng, notoginseng residues and the remaining eight raw materials are boiled and extracted with water, and the filtrate is concentrated and then added with the red ginseng and notoginseng extracts to prepare the preparation. This combination warms the spleen and replenishes qi, removes dampness and resolves blood stasis. It is used for chronic atrophic gastritis caused by spleen and stomach yang deficiency, internal obstruction of dampness and blood stasis, or accompanied by intestinal metaplasia and intraepithelial neoplasia. Symptoms include fullness in the epigastric region, noisy or dull pain in the stomach, decreased appetite, etc. It has a significant therapeutic effect on spleen and stomach yang deficiency, internal obstruction of dampness and blood stasis, etc.

Description

Technical Field

[0001] The present invention relates to a Chinese medicinal composition, and more particularly to a medicinal composition for treating chronic atrophic gastritis, and a preparation method and use thereof. Background Art

[0002] Chronic gastritis (CG) is a common and frequently occurring disease of the digestive system. It is a chronic inflammation of the gastric mucosa caused by various causes such as Helicobacter pylori infection. The clinical symptoms lack specificity and are mainly manifested as upper abdominal pain, distension, belching, loss of appetite, etc. Based on endoscopy and pathological histology, it is divided into chronic non-atrophic gastritis (CNAG) and chronic atrophic gastritis (CAG). Patients with intestinal metaplasia and dysplasia (intraepithelial neoplasia) have an increased risk of gastric cancer and are important targets for secondary prevention of gastric cancer. Chronic atrophic gastritis (CAG) is a common digestive system disease in which the intrinsic glands of the mucosa are atrophied due to repeated damage to the gastric mucosal epithelium by multiple pathogenic factors. The disease is often accompanied by intestinal metaplasia, and a few severe patients even develop dysplasia and develop into gastric cancer. It is reported that CAG is significantly correlated with the incidence of gastric cancer. The canceration rate of this disease is as high as 10% to 14%, with a poor prognosis, which seriously affects the quality of life and work of patients. At present, many studies have shown that "normal gastric mucosa-superficial gastritis-atrophic gastritis-intestinal metaplasia-dysplasia-gastric cancer" is the formation process of gastric cancer. It is believed that CAG is the precancerous lesion stage of gastric cancer. Therefore, timely and effective drug blocking can prevent the disease from developing into gastric cancer or effectively reverse the process of pathological changes. At present, modern medicine mostly uses antibacterial, eradication of Helicobacter pylori infection, proton pump inhibitors, inhibition of gastric acid secretion and other combined application methods of multiple antibiotics. Although it has the advantages of significant efficacy and rapid relief of symptoms, long-term medication is prone to adverse reactions, easy recurrence of the disease, and drug resistance, which greatly limits its clinical application. In recent years, TCM has achieved remarkable results in the treatment of CAG. It can not only effectively improve the patient's related clinical symptoms and delay the progression of gastric mucosal atrophy, but also achieve the effect of prevention and treatment by improving the body's own immunity. In addition, it has the advantages of being simple and easy to operate, having definite clinical efficacy and few adverse reactions. It has been widely used in the treatment of this disease.

[0003] The research team has been committed to the clinical and basic research of TCM prevention and treatment of CAG for more than 20 years. The Yiwei Xiaoyu Recipe (granules) is an empirical prescription summarized on the basis of inheriting the experience of Bayu School. In 2007, the research team published an article entitled "30 cases of chronic atrophic gastritis treated with Yiwei Xiaoyu granules" (Wu Lijia et al., Chinese Journal of Integrated Traditional and Western Medicine for Digestion, 2007, 15(1): 57-58), reporting that the Yiwei Xiaoyu Recipe (granules) is composed of red ginseng, hericium erinaceus, Panax notoginseng, fleabane, coix seed, dendrobium, ganoderma lucidum, and galangal. The experimental results suggest that the prescription has the effect of blocking and reversing atrophy, intestinal metaplasia and dysplasia in patients. The prescription of Yiwei Xiaoyu Granule was adjusted to red ginseng, Panax notoginseng, Sauerkraut seeds, Atractylodes macrocephala, Angelica sinensis, Coix seeds, Fritillaria thunbergii, Curcuma zedoaria, Faroe sea, and Dendrobium candidum (Liu Xia et al., Chinese Journal of Traditional Chinese Medicine, 2018, 33(4): 1605-1607). Among them, red ginseng replenishes qi and strengthens the spleen, Panax notoginseng promotes blood circulation and removes blood stasis as the main medicine, Sauerkraut seeds soothe the liver and regulate qi, harmonize the stomach and relieve pain, and Angelica sinensis replenishes blood and promotes blood circulation, and nourishes the stomach and yin as the auxiliary medicine. This prescription is used for chronic superficial gastritis with insufficient spleen yang and stomach yin, qi stagnation and blood stasis, and atrophic gastritis with intestinal metaplasia and dysplasia. The relevant syndromes and functions of conventional Chinese patent medicines for the treatment of chronic gastritis are shown in Table 1.

[0004] Table 1 Chinese patent medicines related to the treatment of chronic gastritis

[0005]

[0006] Most of the drugs listed in Table 1 are mainly used to treat chronic non-atrophic gastritis, chronic superficial gastritis, functional dyspepsia, reflux esophagitis, or chronic atrophic gastritis with the above symptoms. Currently, there are few Chinese patent medicines that are clinically positioned for chronic atrophic gastritis and have been marketed. The early drug clinical positioning of this project team was to treat chronic superficial gastritis and atrophic gastritis with spleen yang and stomach yin deficiency, qi stagnation and blood stasis syndrome. In recent years, based on clinical experience, the etiology and pathogenesis have been explored and it has been found that chronic atrophic gastritis has a complex syndrome of spleen and stomach yang deficiency and dampness and blood stasis, that is, chronic atrophic gastritis caused by spleen and stomach yang deficiency and dampness and blood stasis; although the two have the same name in Western medicine, the syndromes in Chinese medicine are different. In summary, there is currently a lack of therapeutic drugs for chronic atrophic gastritis in clinical practice, and there is a major clinical need that has not been met. Therefore, it is very necessary to develop new Chinese medicines for the treatment of chronic atrophic gastritis caused by spleen and stomach yang deficiency and dampness and blood stasis syndrome, which has a huge market demand. Summary of the invention

[0007] The purpose of the present invention is to provide a pharmaceutical composition with definite efficacy for treating chronic atrophic gastritis caused by spleen and stomach yang deficiency, dampness and blood stasis, etc. Based on the early research of this subject team, according to precise clinical positioning, it is determined to treat chronic atrophic gastritis caused by spleen and stomach yang deficiency, dampness and blood stasis, and further optimize the prescription to obtain the pharmaceutical composition of the present invention. Another purpose of the present invention is to provide a preparation method and use of the pharmaceutical composition.

[0008] The pharmaceutical composition for treating chronic atrophic gastritis of the present invention is a preparation prepared from active ingredients and pharmaceutically acceptable excipients, wherein the active ingredients are prepared from raw materials in the following weight ratio:

[0009] Red ginseng 4-8g, Atractylodes macrocephala 12-18g, Panax notoginseng 4-8g, Angelica sinensis 4-6g, Curcuma 8-12g, Coix seed 12-18g, Fritillaria thunbergii 12-18g, Dendrobium candidum 8-12g, Fa Luo Hai 12-18g, Sago seed 8-12g.

[0010] Preferably, it is prepared from the following bulk drug in the following weight ratio:

[0011] Red ginseng 6g, Atractylodes macrocephala 15g, Panax notoginseng 6g, Angelica sinensis 5g, Curcuma 10g, Coix seed 15g, Fritillaria thunbergii 15g, Dendrobium candidum 10g, Fa Luo Hai 15g, and Sago seed 10g.

[0012] Among them, in the pharmaceutical composition described in the present invention, Faluohai is a variety included in the 2015 edition of "Sichuan Province Traditional Chinese Medicine Preparation Specifications", and other raw materials are varieties included in the 2020 edition of "Chinese Pharmacopoeia", all of which comply with the relevant regulations. The preparation is an oral drug preparation absorbed through the gastrointestinal tract.

[0013] The present invention also provides a method for preparing the above-mentioned pharmaceutical composition, which comprises the following steps:

[0014] (1) Weigh the API according to the weight ratio;

[0015] (2) extracting red ginseng and Panax notoginseng by refluxing with 50% to 80% ethanol by volume, filtering, and recovering ethanol by decompressing the filtrate to obtain red ginseng and Panax notoginseng extracts for later use;

[0016] (3) boiling and extracting the red ginseng, Panax notoginseng residues and the other eight raw materials with water, filtering, concentrating the filtrate, adding the red ginseng and Panax notoginseng extracts obtained in step (2), drying, and adding auxiliary materials to prepare a preparation.

[0017] Optionally, the ethanol reflux extraction in step (2) is performed at least twice, each time adding 50%-80% ethanol in an amount of 7-10 times the total weight of red ginseng and Panax notoginseng, and each time refluxes for 1-2 hours.

[0018] Optionally, the water decoction extraction in step (3) is performed at least twice, each time adding water in an amount of 8-12 times the total weight of red ginseng, Panax notoginseng residues and the other eight raw materials, and each time decocting for 1-2 hours.

[0019] The pharmaceutically acceptable excipients described in the present invention include, but are not limited to, fillers: one or more of soluble starch, dextrin, lactose, mannitol, sorbitol, sucrose, etc. according to the needs of the pharmaceutical industry; disintegrants: one or more of sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose, etc.; suspending agents: one or more of carbomer, xanthan gum, tragacanth gum, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, carrageenan, PVP, etc.; lubricants / glidants: one or more of micro-powdered silica gel, talc, magnesium stearate, etc.; flavoring agents: one or more of sucralose, stevioside, aspartame, peach flavor, strawberry flavor, lemon flavor, etc.; wetting agents: one or more of poloxamer, sodium lauryl sulfate, polyethylene glycol, etc.; coloring agents: caramel pigment, etc.; thickeners: pectin, etc.

[0020] The preparation is an oral drug preparation, and the oral drug preparation is preferably made into a granule. In the early research of this team, the drug was directly crushed into fine powder by red ginseng and Panax notoginseng, and the dosage of the preparation was large (15g each time, 4 times a day), the taste was poor, and the compliance was poor. The present invention greatly reduces the dosage of the preparation after extracting red ginseng and Panax notoginseng by the above method, and significantly improves the taste and compliance of the drug.

[0021] The present invention is based on the knowledge of chronic atrophic gastritis and the etiology and pathogenesis of spleen and stomach yang deficiency, dampness and blood stasis internal obstruction syndrome, etc., and can relieve clinical discomfort symptoms by warming spleen yang, invigorating qi and relieving pain, and can also transport and transform water and dampness, remove blood stasis and dissipate stagnation, and improve spleen and stomach function. In the prescription, red ginseng invigorates qi and produces body fluid, white atractylodes invigorates spleen and invigorates qi and eliminates dampness, angelica, curcuma, and Panax notoginseng nourish blood and promote blood circulation, dissipate blood stasis and relieve pain, coix seed and thungbean bulb invigorate spleen and eliminate dampness, eliminate phlegm and dissipate stagnation, dendrobium invigorates stomach and produces body fluid, nourishes yin and clears heat, and saro seeds and farrow sea soothe the liver and promote qi, harmonize the stomach and eliminate stagnation. The whole prescription warms the spleen and stomach, invigorates qi, invigorates blood circulation and resolves phlegm, and is used to treat spleen and stomach yang deficiency, phlegm and dampness stasis and mutual obstruction of the syndrome. It is clinically used to treat chronic atrophic gastritis caused by deficiency of spleen and stomach yang qi, internal obstruction of dampness and blood stasis, or accompanied by intestinal metaplasia and intraepithelial neoplasia, with symptoms such as epigastric fullness, stomach noise or dull pain, decreased appetite, etc. It has a definite effect and can be used in the preparation of medicines for preventing and treating chronic atrophic gastritis caused by deficiency of spleen and stomach yang qi, internal obstruction of dampness and blood stasis, etc., especially for deficiency of spleen and stomach yang qi, internal obstruction of dampness and blood stasis.

[0022] Furthermore, the medicine for preventing and treating chronic atrophic gastritis caused by deficiency of spleen and stomach yang qi, dampness and blood stasis syndrome, etc., is composed of 6g of red ginseng, 15g of white atractylodes, 6g of panax notoginseng, 5g of angelica, 10g of curcuma, 15g of coix seed, 15g of fritillaria thunbergii, 10g of dendrobium, 15g of falanghai, and 10g of sauerkraut seeds, wherein red ginseng and panax notoginseng are extracted by reflux with 50-80% ethanol, filtered, and the filtrate is decompressed to recover ethanol to obtain red ginseng and panax notoginseng extracts for later use; red ginseng, panax notoginseng residues and the other eight flavors are decocted with water for extraction, filtered, the filtrate is concentrated, the above-mentioned red ginseng and panax notoginseng extracts are added, and oral pharmaceutical preparations such as granules, pills, etc. are prepared according to conventional methods.

[0023] In recent years, based on the results of previous clinical trials and after further accumulating clinical experience, the project team explored the etiology and pathogenesis, accurately positioned the clinical situation based on TCM syndrome differentiation and clinical efficacy, adjusted the dosage and compatibility, and finally optimized the prescription to: 6g red ginseng, 15g white atractylodes, 6g Panax notoginseng, 5g angelica, 10g Curcuma, 15g Coix seeds, 15g Fritillaria thunbergii, 10g Dendrobium, 15g Fa Luo Hai, 10g Salaciae seeds, made into granules, in which red ginseng and white atractylodes are reused to warm and nourish the spleen (the dosage of red ginseng is increased from 5g in the original formula to 6g, and that of white atractylodes is increased from 10g to 15g) , red ginseng to replenish qi and produce body fluid, white macrocephala to strengthen the spleen, invigorate qi and dry dampness are the main ingredients, Panax notoginseng, Angelica sinensis, and Curcuma zedoaria to promote blood circulation, unblock collaterals and relieve pain are the ministers (Panax notoginseng is increased from 3g in the original formula to 6g, Angelica sinensis is reduced from 10g to 5g, and Curcuma zedoaria is increased from 6g to 10g), Coix seed and Fritillaria thunbergii to strengthen the spleen and eliminate dampness, eliminate phlegm and disperse nodules, Dendrobium to benefit the stomach, produce body fluid, nourish yin and clear away heat are the auxiliary ingredients (Coix seed is reduced from 30g in the original formula to 15g, Fritillaria thunbergii is increased from 10g to 15g, and Dendrobium 15g is reduced from 15g to 10g), Faroe sea and Sauerkraut are used to promote qi and relieve bloating (Faroe sea 10g is increased to 15g, and Sauerkraut 15g is reduced to 10g).

[0024] Compared with the prior art, the present invention has at least the following beneficial effects:

[0025] This combination warms the spleen and replenishes qi, removes dampness and resolves blood stasis. It is used for chronic atrophic gastritis caused by spleen and stomach yang deficiency and internal obstruction of dampness and blood stasis, or accompanied by intestinal metaplasia and intraepithelial neoplasia. Symptoms include epigastric fullness, stomach noise or dull pain, decreased appetite, etc. Due to the precise clinical positioning (spleen and stomach yang deficiency and internal obstruction of dampness and blood stasis syndrome), the prescription corresponds to the syndrome, and the clinical efficacy is significantly improved (the total effective rate of treatment of glandular atrophy, intestinal metaplasia IM and atypical hyperplasia Dys is increased by about 10% compared with before). DETAILED DESCRIPTION

[0026] The content of the invention of the present invention is further described in detail below through specific implementation methods. However, this should not be understood as the scope of protection of the present invention being limited to the following examples. Without departing from the above technical ideas of the present invention, various substitutions or changes made according to common technical knowledge and customary means in the art should be included in the scope of the present invention.

[0027] Example 1

[0028] Take 6kg of red ginseng, 15kg of Atractylodes macrocephala, 6kg of Panax notoginseng, 5kg of Angelica sinensis, 10kg of Curcuma zedoaria, 15kg of Coix seeds, 15kg of Fritillaria thunbergii, 10kg of Dendrobium candidum, 15kg of Sea of ​​​​Falonia ovata, and 10kg of Sauerkraut seeds. Among them, the Panax notoginseng is crushed and refluxed with 60% ethanol for two times with red ginseng, the first time is increased by 8 times, the second time is increased by 7 times, each time is refluxed for 1.5 hours, filtered, the filtrate is decompressed to recover ethanol, and concentrated to obtain red ginseng and Panax notoginseng extracts for standby use; the Sauerkraut seeds are crushed, boiled and extracted three times with red ginseng, Panax notoginseng residues and the remaining seven raw materials, the first time is increased by 12 times, the second and third times are increased by 10 times respectively, each time is boiled for 1.5 hours, filtered, the filtrate is concentrated, the above-mentioned red ginseng and Panax notoginseng extracts are added, dried, an appropriate amount of dextrin is added according to a conventional method, mixed, and made into granules.

[0029] Example 2

[0030] Take 4kg of red ginseng, 18kg of Atractylodes macrocephala, 4kg of Panax notoginseng, 6kg of Angelica sinensis, 8kg of Curcuma zedoaria, 12kg of Coix seeds, 18kg of Fritillaria thunbergii, 8kg of Dendrobium officinale, 12kg of Sea of ​​​​Falonia ovata, and 12kg of Sauerkraut seeds. Among them, the Panax notoginseng is crushed and refluxed with 80% ethanol for two times with the red ginseng, the first time it is added 10 times, the second time it is added 8 times, each time it is refluxed for 2 hours, filtered, the filtrate is decompressed to recover ethanol, and concentrated to obtain red ginseng and Panax notoginseng extracts for standby use; the Sauerkraut seeds are crushed, and the red ginseng, Panax notoginseng residues and the remaining seven raw materials are boiled and extracted three times with water, the first time it is added 10 times, the second and third times are added 8 times respectively, each time it is boiled for 2 hours, filtered, the filtrate is concentrated, the above-mentioned red ginseng and Panax notoginseng extracts are added, dried, and an appropriate amount of dextrin is added according to a conventional method. Mix well to make granules.

[0031] Example 3

[0032] Take 8kg of red ginseng, 12kg of Atractylodes macrocephala, 8kg of Panax notoginseng, 4kg of Angelica sinensis, 12kg of Curcuma zedoaria, 18kg of Coix seeds, 12kg of Fritillaria thunbergii, 12kg of Dendrobium candidum, 18kg of Sea of ​​​​Falonia ovata, and 8kg of Sauerkraut seeds. Among them, the Panax notoginseng is crushed and refluxed with 50% ethanol for extraction three times with the red ginseng, the first time adding 8 times, the second and third times adding 7 times, each time reflux for 1 hour, filtered, the filtrate is decompressed to recover ethanol, and concentrated to obtain red ginseng and Panax notoginseng extracts for standby use; the Sauerkraut seeds are crushed, boiled and extracted twice with red ginseng, Panax notoginseng residues and the remaining seven raw materials, the first time adding 12 times, the second time adding 10 times, each time boiling for 2 hours, filtered, the filtrate is concentrated, the above-mentioned red ginseng and Panax notoginseng extracts are added, dried, and an appropriate amount of dextrin is added according to a conventional method. Mix well to make granules.

[0033] Example 4

[0034] Take 7kg of red ginseng, 14kg of Atractylodes macrocephala, 5kg of Panax notoginseng, 6kg of Angelica sinensis, 9kg of Curcuma zedoaria, 14kg of Coix seeds, 14kg of Fritillaria thunbergii, 9kg of Dendrobium officinale, 12kg of Sea of ​​​​Falonia ovata, and 9kg of Sauerkraut seeds. Among them, Sauerkraut slices, and reflux extracts with 70% ethanol twice with red ginseng, the first time adding 9 times, the second time adding 8 times, each time reflux 2 hours, filter, decompress the filtrate to recover ethanol, concentrate to obtain red ginseng and Panax notoginseng extracts, and set aside; Sauerkraut seeds are crushed, boiled and extracted three times with red ginseng, Panax notoginseng residues and the remaining seven raw materials, the first time adding 10 times, the second and third times adding 8 times respectively, each time boiling for 1.5 hours, filter, concentrate the filtrate, add the above red ginseng and Panax notoginseng extracts, add dextrin, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and cross-linked polyvinylpyrrolidone according to the conventional method, mix well, and make pills.

[0035] The main clinical symptoms of chronic atrophic gastritis include fullness and pain in the epigastric region, heartburn and indigestion, abnormal stool, weight loss, anemia, etc. The drug composition of this prescription is precise and the clinical efficacy shows that it has a significant effect in treating chronic atrophic gastritis (deficiency of spleen and stomach yang qi, dampness and blood stasis, etc.).

[0036] Further pharmacodynamic study results show that the pharmaceutical composition of the present invention has a definite therapeutic effect in treating chronic atrophic gastritis and has good clinical value and market prospects.

[0037] The beneficial effects of the pharmaceutical composition of the present invention are illustrated below through specific pharmacodynamic study results.

[0038] Preparation of test drugs: According to the preparation method of Example 1, 0.6 kg of red ginseng, 1.5 kg of white atractylodes, 0.6 kg of Panax notoginseng, 0.5 kg of angelica, 1.0 kg of Curcuma, 1.5 kg of Coix seeds, 1.5 kg of Fritillaria thunbergii, 1.0 kg of Dendrobium officinale, 1.5 kg of Fa Luo Hai, and 1.0 kg of Salacia strychnifolia were weighed, among which Panax notoginseng was crushed and refluxed with 60% ethanol for two times with red ginseng, the first time adding 8 times and the second time adding 7 times, each time refluxed for 1.5 hours, filtered , the filtrate is decompressed to recover ethanol, and concentrated to obtain red ginseng and Panax notoginseng extracts for later use; crush the seeds of Sauerkraut, add water to red ginseng, Panax notoginseng residues and the remaining seven herbs, and boil and extract three times. The first time, add 12 times, and the second and third times, respectively, add 10 times. Each time, boil for 1.5 hours, filter, concentrate the filtrate, add the above-mentioned red ginseng and Panax notoginseng extracts, mix evenly, that is, the experimental drug (YWXY) of the present invention, use purified water to make the required concentration for oral administration, and the dosage is calculated according to the original drug (unit: g / kg). 1. Experimental study on the effect of treating chronic atrophic gastritis

[0039] 1.1 Effects of MNNG on the rat model of chronic atrophic gastritis induced by multiple factors

[0040] The SD rats (all males) that passed the quarantine were given MNNG gavage and free drinking, combined with hunger and satiety disorder to establish a chronic atrophic gastritis rat model for 7 months. Fifty rats with successful modeling were randomly divided into 5 groups, namely the model group (purified water), high-, medium- and low-dose groups of the experimental drug (11, 5.5, and 2.75 g of crude drug / kg / d), and the Wei Fuchun capsule group (0.45 g of content / kg / d), with 10 rats in each group. Another 10 untreated rats were taken as the solvent control group. The drug was administered by gavage once a day for 3 consecutive months. 24 hours after the last administration, the rats were anesthetized and blood and stomach were taken to detect serum enzyme indicators and gastric-related indicators. SPSS13.0 for windows was used for data statistical analysis, and the numerical values ​​were used. The results were tested with t' test, and P < 0.05 was considered statistically significant (Table 1).

[0041] Table 1 Effects of the drugs of the present invention on serum enzyme indexes in rats with chronic atrophic gastritis caused by MNNG combined with multiple factors

[0042]

[0043] Note: Compared with the model group: *P<0.05, **P<0.01

[0044] As can be seen from Table 1, the high-dose and medium-dose groups of the experimental drug can significantly increase the serum PGR of CAG model rats and reduce the levels of IL-1β and TNF-α, which is statistically significant compared with the model group; the low-dose group of the experimental drug has a trend of increasing the serum PGR of CAG model rats and reducing the levels of IL-1β and TNF-α.

[0045] Pathological results showed that high and medium doses of the test drug had a significant improvement and repair effect on gastric mucosal atrophy caused by modeling.

[0046] 1.2 Effects on the rat chronic atrophic gastritis model induced by the combined method (sodium deoxycholate + ethanol)

[0047] The SD rats (half male and half female) that passed the quarantine were fed with sodium deoxycholate and ethanol alternately for 5 months to establish a rat model of chronic atrophic gastritis. Fifty rats with successful modeling were randomly divided into 5 groups, namely the model group (purified water), high-, medium- and low-dose groups of the experimental drug (11, 5.5, and 2.75 g / kg / d), and the Weifuchun capsule group (0.45 g content / kg / d), with 10 rats in each group. Another 10 untreated rats were taken as the solvent control group. The drug was administered by gavage once a day for 3 consecutive months. 24 hours after the last administration, the rats were anesthetized and blood was collected and the stomach was removed to detect serum enzyme indicators and gastric-related indicators. SPSS13.0 for windows was used for data statistical analysis, and the numerical values ​​were used. The results were tested with t' test, and P < 0.05 was considered statistically significant (Table 2).

[0048] Table 2 Effects of the drugs of the present invention on serum enzyme indexes in rats with chronic atrophic gastritis induced by sodium deoxycholate + ethanol

[0049]

[0050] Note: Compared with the model group: *P<0.05, **P<0.01

[0051] As can be seen from Table 2, the high-dose group of the experimental drug can significantly increase the serum PGR content of CAG model rats, and reduce the levels of IL-1β and TNF-α, which is statistically significant compared with the model group; the medium-dose group can significantly increase the serum PGR content of CAG model rats, and there is a trend of reducing the levels of IL-1β and TNF-α, which is statistically significant compared with the model group; the low-dose group of the experimental drug has a trend of increasing the serum PGR of CAG model rats and reducing the levels of IL-1β and TNF-α.

[0052] Pathological results showed that high and medium doses of the test drug had a significant improvement and repair effect on gastric mucosal atrophy caused by modeling.

[0053] 2. Experimental study on gastric motility

[0054] 2.1 Effects on gastric emptying in mice

[0055] 60 mice that passed the quarantine were randomly divided into 6 groups, namely, vehicle control group, model control group, high-, medium- and low-dose groups of the experimental drug (22, 11, and 5.5 g crude drug / kg), and Weifuchun capsule group (0.9 g content / kg), with 10 mice in each group, half of which were male and half were female. The drugs were administered continuously for 5 days. One hour after the last administration, except for the vehicle control group, the other groups were intraperitoneally injected with 0.5 mg / kg of atropine sulfate. Ten minutes later, they were gavaged with 0.8 ml of semisolid paste each. Twenty minutes after gavage with semisolid paste, the animals were killed, the stomach weight was weighed, and the stomach residual rate was calculated according to the following formula: stomach residual rate (%) = (total stomach weight - stomach net weight) / semisolid paste weight × 100%. SPSS13.0 for windows was used for data statistical analysis, and the numerical values ​​were adopted The results were tested with t' test, and P < 0.05 was considered statistically significant (Table 6).

[0056] Table 6 Effect of the drugs of the present invention on gastric emptying in mice

[0057]

[0058]

[0059] Note: Compared with the model group: *P<0.05, **P<0.01

[0060] As shown in Table 6, the high and medium dose groups of the experimental drug can significantly reduce the gastric residual rate and promote gastric motility, which is statistically significant compared with the model group; the low dose group of the experimental drug has a tendency to reduce the gastric residual rate, indicating that the experimental drug has the effect of promoting gastric emptying in mice.

[0061] In summary, the results of pharmacodynamic studies show that the pharmaceutical composition of the present invention can significantly reduce the gastric tissue pathological scores of rats with chronic atrophic gastritis models, significantly reduce the levels of IL-1β and TNF-α in their serum, increase PGR activity, and improve abnormal pathological changes in gastric tissue; it significantly increases the gastric emptying rate of experimental animals, indicating that the composition of the present invention has the effects of treating chronic atrophic gastritis and promoting gastrointestinal motility. Further clinical practice and application have shown that the composition of the present invention (granules) has significant clinical efficacy in treating chronic atrophic gastritis caused by spleen and stomach yang deficiency, dampness and blood stasis, etc., and can significantly improve symptoms such as fullness, pain, heartburn and indigestion in the epigastric region, significantly improve TCM syndromes, and have no obvious adverse reactions; it shows that the composition of the present invention has the effects of warming the spleen and replenishing qi, removing dampness and removing blood stasis, and has a definite effect in treating chronic atrophic gastritis caused by spleen and stomach yang deficiency, dampness and blood stasis, and has good The invention has good clinical application value and market prospect; compared with the original prescription (5g of red ginseng, 3g of Panax notoginseng, 15g of Semen Sinensis, 10g of Atractylodes macrocephala, 10g of Angelica sinensis, 30g of Coix seeds, 10g of Fritillaria thunbergii, 6g of Curcuma zedoaria, 10g of Herba Faereirae, 15g of Dendrobium), the composition of the invention is used to treat chronic atrophic gastritis caused by deficiency of spleen and stomach yang qi and internal obstruction of dampness and blood stasis, and the total effective rate of the main therapeutic indexes of glandular atrophy, intestinal metaplasia IM and atypical hyperplasia Dys is increased by about 10% compared with the original prescription.

[0062] Although the present invention is described herein with reference to the illustrative embodiments of the present invention, it should be understood that those skilled in the art can design many other modifications and implementations, which will fall within the scope and spirit of the principles disclosed in the present application. More specifically, within the scope disclosed in the present application, multiple variations and improvements can be made to the components and / or layout of the subject combination layout. In addition to the variations and improvements made to the components and / or layout, other uses will also be apparent to those skilled in the art.

Claims

1. A pharmaceutical composition for treating chronic atrophic gastritis, characterized in that: It is a preparation made from active ingredients and pharmaceutically acceptable excipients, wherein the active ingredients are prepared from raw materials in the following weight ratio: Red ginseng 4-8g, Atractylodes macrocephala 12-18g, Panax notoginseng 4-8g, Angelica sinensis 4-6g, Curcuma 8-12g, Coix seed 12-18g, Fritillaria thunbergii 12-18g, Dendrobium candidum 8-12g, Fa Luo Hai 12-18g, Sago seed 8-12g.

2. The pharmaceutical composition for treating chronic atrophic gastritis according to claim 1, characterized in that: The active ingredient is prepared from the following raw material medicine in the following weight ratio: Red ginseng 6g, Atractylodes macrocephala 15g, Panax notoginseng 6g, Angelica sinensis 5g, Curcuma 10g, Coix seed 15g, Fritillaria thunbergii 15g, Dendrobium candidum 10g, Fa Luo Hai 15g, Sago seed 10g.

3. The pharmaceutical composition for treating chronic atrophic gastritis according to claim 1 or 2, characterized in that: The preparation is an oral pharmaceutical preparation absorbed through the gastrointestinal tract.

4. The method for preparing the pharmaceutical composition for treating chronic atrophic gastritis according to claim 1 or 2, characterized in that: It includes the following steps: (1) Weigh the API according to the weight ratio; (2) extracting red ginseng and Panax notoginseng with 50% to 80% ethanol by volume, filtering, and recovering ethanol from the filtrate under reduced pressure to obtain red ginseng and Panax notoginseng extracts for later use; (3) The red ginseng, Panax notoginseng residues and the other eight raw materials are boiled in water for extraction, filtered, and the filtrate is concentrated. The red ginseng and Panax notoginseng extracts obtained in step (2) are added, dried, and prepared into a preparation.

5. The method for preparing the pharmaceutical composition for treating chronic atrophic gastritis according to claim 4, characterized in that: In step (2), the ethanol reflux extraction is performed at least twice, each time adding 50-80% ethanol in an amount of 7-10 times the total weight of red ginseng and Panax notoginseng, and each time reflux is performed for 1-2 hours.

6. The method for preparing the pharmaceutical composition for treating chronic atrophic gastritis according to claim 5, characterized in that: In step (3), the extraction is performed by decoction at least twice, each time adding water in an amount of 8-12 times the total weight of the red ginseng, Panax notoginseng residues and the other eight raw materials, and each time the decoction is performed for 1-2 hours.

7. The method for preparing the pharmaceutical composition for treating chronic atrophic gastritis according to claim 6, characterized in that: In step (3), excipients are added during the preparation of the preparation.

8. Use of the pharmaceutical composition according to claim 1 or 2 in the preparation of a medicament for preventing and treating chronic atrophic gastritis caused by deficiency of spleen and stomach yang qi and internal obstruction of dampness and blood stasis.

9. A pharmaceutical composition for treating chronic atrophic gastritis, characterized in that: As a medicine for preventing and treating chronic atrophic gastritis caused by deficiency of spleen and stomach yang qi and internal obstruction of dampness and blood stasis, the medicine is prepared from 6g of red ginseng, 15g of white atractylodes, 6g of panax notoginseng, 5g of angelica, 10g of curcuma, 15g of coix seeds, 15g of fritillaria thunbergii, 10g of dendrobium, 15g of falanghai and 10g of sauerkraut seeds, wherein red ginseng and panax notoginseng are extracted by reflux with ethanol with a volume fraction of 50%-80%, filtered, and the filtrate is decompressed to recover the ethanol to obtain red ginseng and panax notoginseng extracts for standby use; red ginseng, panax notoginseng residues and the other eight raw materials are decocted with water for extraction, filtered, the filtrate is concentrated, the red ginseng and panax notoginseng extracts are added, and then the extracts are prepared into oral pharmaceutical preparations.

10. The pharmaceutical composition for treating chronic atrophic gastritis according to claim 9, characterized in that: Ethanol reflux extraction is performed at least twice, each time adding 50-80% ethanol in an amount of 7-10 times the total weight of red ginseng and Panax notoginseng, and each time reflux is performed for 1-2 hours; water decoction extraction is performed at least twice, each time adding water in an amount of 8-12 times the total weight of red ginseng, Panax notoginseng residues and the other eight raw materials, and each time decoction is performed for 1-2 hours.

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