Traditional Chinese medicine composition for treating non-erosive gastroesophageal reflux as well as preparation method and application thereof

Abstract

The invention provides a traditional Chinese medicine composition for treating non-erosive gastroesophageal reflux as well as a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. On one hand, the invention provides a traditional Chinese medicine composition formula for treating non-erosive gastroesophageal reflux; secondly, the invention provides a traditional Chinese medicine composition for treating non-erosive gastroesophageal reflux. Thirdly, the invention provides a preparation method of the traditional Chinese medicine composition for treating non-erosive gastroesophageal reflux. In the fourth aspect, the invention further provides application of the traditional Chinese medicine composition in preparation of medicine for treating non-erosive gastroesophageal reflux.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition for treating non-erosive gastroesophageal reflux, and a preparation method and application thereof. Background Art

[0002] Gastroesophageal reflux disease (GERD) refers to chronic symptoms or mucosal damage caused by abnormal reflux of gastric contents into the esophagus. Its typical symptoms are reflux and heartburn, which may be accompanied by (or not accompanied by) extraesophageal symptoms. GERD can be divided into non-erosive gastroesophageal reflux disease (NERD), reflux esophagitis, and Barrett's esophagus according to the endoscopic mucosal condition. Among them, NERD is the most common. According to the "2020 Chinese Gastroesophageal Reflux Disease Expert Consensus", non-erosive gastroesophageal reflux disease is defined as: having typical symptoms such as heartburn, reflux, etc., or atypical symptoms such as chest pain, belching, etc., and endoscopic examination has excluded positive conditions such as esophageal mucosal damage and Barrett's esophagus, and a clear diagnosis of NERD is made.

[0003] At present, the global incidence of GERD is 2.5% to 51.2%, and the incidence in my country is 5% to 10%, which is increasing year by year, while NERD accounts for about 70% of GERD. Epidemiological surveys show that when the interval between the occurrence of heartburn or reflux symptoms within one week is used as the clinical diagnostic standard, the global incidence is 13.3%. The prevalence of GERD in community residents in the UK is 21%; in the United States, a national random telephone survey on GERD showed that the incidence of GERD in the United States is 14%, of which the night incidence is 10%; the prevalence of GERD in urban residents in Brazil is 7.3%. Among Asian countries, the incidence of GERD in Japan is 17.9%, and the prevalence of erosive esophagitis and NERD is 8.6% and 10.9% respectively; the incidence in Tehran, northern Iran, is 6.8%. In my country, the incidence of GERD in different cities is significantly different, with 1.7% in Guangzhou, 5.1% in Wuhan, and 6.4% in Shanghai; the prevalence in the community population is 7.7%, and the prevalence in men is significantly higher than that in women, and the prevalence in the northwest is significantly higher than that in the east China. Due to factors such as population aging, smoking, and obesity, the incidence of GERD is increasing year by year. As the incidence increases, medical costs are also gradually increasing. Studies show that the average monthly medical expenses for Japanese GERD patients aged 20 to 59 in 2014 were US$266, which is 2.4 times the average medical expenses in Japan during the same period.

[0004] Western medicine theory believes that lower esophageal sphincter (LES) dysfunction is an important cause of non-erosive gastroesophageal reflux disease. Proton pump inhibitors (PPIs) are the first choice of drugs. They are relatively safe for short-term use, but long-term use will lead to many side effects, such as: osteoporosis and increased risk of brittle fractures; decreased cognitive ability and increased risk of Alzheimer's disease; affected the absorption of clopidogrel; increased risk of chronic kidney disease, etc. In addition, H2 receptor antagonists (H2RA), potassium ion competitive acid blockers (P-CAB), mucosal protectants, antacids, and prokinetic drugs are often used in combination. Endoscopic treatment or surgical treatment can be used for refractory patients. Due to the uncertainty and complexity of the pathogenesis of this disease, the efficacy of Western medicine in treating this disease is unstable, and it is difficult to achieve the purpose of radical cure. Symptoms are prone to recurrence after drug withdrawal.

[0005] Traditional Chinese medicine has a history of thousands of years in preventing and treating NERD. Although there is no relevant record of the name of "non-erosive gastroesophageal reflux disease" in ancient Chinese medical books, according to its clinical symptoms and pathological characteristics, this disease can be classified into the category of "regurgitation of acid", "swallowing acid", "esophageal reflux" and other diseases in traditional Chinese medicine. It is mainly caused by pathological factors such as invasion of exogenous evil, improper diet, emotional disorder, and spleen deficiency. The key pathogenesis is that the stomach fails to descend and the stomach qi goes up. "Lingshu·Jingmai" says: "The stomach foot yangming pulse goes along the throat and enters the supraclavicular pelvis, the spleen foot taiyin pulse goes along the throat and connects to the root of the tongue... The liver foot jueyin pulse goes along the throat and enters the forehead." This shows that this disease is closely related to the liver, stomach, and spleen in the esophagus. In addition, "Suwen" says "sour is the taste of liver wood. Because fire wins and controls metal, it cannot calm wood, so the liver wood is too strong, so it is sour", which discusses the failure of lung qi to descend, metal to control wood, and stomach qi going up, which causes acid and water to rise. All diseases originate from Qi. The Jingyue Complete Works: Heart and Abdominal Pain also discusses this: “Stomach disease symptoms are mostly caused by food, cold, or Qi stagnation. However, food and cold are also related to Qi. If food is not eaten, Qi will stagnate, and if cold is retained, Qi will stagnate. Therefore, the key to treating pain is to observe whether it is caused by real evil, and the main treatment should be to regulate Qi.

[0006] Many prescriptions for treating such diseases are recorded in Treatise on Febrile Diseases and Synopsis of the Golden Chamber. These prescriptions can be used flexibly and appropriately according to the specific symptoms of the patient, so as to achieve the therapeutic purposes of harmonizing yin and yang, regulating qi, resolving phlegm and fluid, and clearing dampness and turbidity. For example, Gardenia Licorice and Chi Decoction and Rhubarb and Coptis Decoction for Purging the Heart can reduce esophageal mucosal damage in rats with reflux esophagitis and inhibit inflammation; Wumei Pills can not only effectively improve the symptoms of GERD, but also enhance the tension of the lower esophageal sphincter and the clearance ability of the esophagus; Danzhi Xiaoyao Powder combined with Zuojin Pills has high safety and efficacy in treating GERD and can improve gastrointestinal hormone levels.

[0007] According to numerous research reports on the treatment of GERD with traditional Chinese medicine prescriptions, it can be seen that traditional Chinese medicine prescriptions have disadvantages such as low efficacy and high recurrence rate.

[0008] In addition, the rough preparation process of traditional Chinese medicine for non-erosive gastroesophageal reflux restricts the efficacy of the medicine.

[0009] In view of this, the present invention provides a traditional Chinese medicine composition for treating non-erosive gastroesophageal reflux and a preparation method and application thereof. Summary of the invention

[0010] The technology of the present invention comes from the clinical experience of Lu Fang, a master of traditional Chinese medicine. It is rooted in the classical theory of traditional Chinese medicine and combined with the changes in people's lifestyles and mental psychology in the modern context. It is believed that the pathogenesis of this disease is closely related to the liver, and "depression" and "heat" are the key to the pathogenesis of this disease. Stagnation of liver qi, which turns into heat over time, and evil heat invades the stomach, then liver and stomach stagnation and heat. Stagnation of liver qi, stagnation of heat in the gallbladder, then gallbladder heat invades the stomach. Weak spleen and stomach, and imbalance of ascending and descending, then stomach qi goes up. The treatment should focus on soothing the liver and relieving depression, harmonizing the stomach and reducing adverse reactions, and promoting qi and dispersing stagnation.

[0011] According to the basic etiology and pathogenesis of NERD, this prescription treats NERD mainly by soothing the liver and relieving depression, harmonizing the stomach and relieving adverse reactions. The bupleurum in the prescription is bitter and slightly cold, and mainly enters the liver and gallbladder meridians. "Compendium of Materia Medica 100 Records" states: "Bupleurum is a medicine for the intestines and stomach. ... With its light and clear smell, it can dredge stagnant qi in stubborn soil." Wood depression should be relieved by soothing the liver and relieving depression, regulating qi and harmonizing the stomach. As the main medicine, warm turmeric and white peony root can promote qi and relieve depression, nourish blood and soften the liver, and can clear the heat of the liver and gallbladder. As the assistant medicine, walnut is salty in taste. The nature is neutral, the oyster tastes salty and is slightly cold, it can eliminate phlegm, soften hard masses, dissipate blood stasis and resolve nodules, reduce acid and relieve pain, Coptis chinensis is good at clearing heart fire, reducing liver fire, and clearing stomach fire, liver fire will not go against the stomach if it is cleared, and the stomach qi will no longer go against the stomach; Pinellia ternata and Magnolia officinalis promote qi and resolve nodules, reduce adverse reactions and resolve phlegm, Citrus aurantium enters the liver and gallbladder meridians, soothes the liver and breaks up qi, eliminates accumulation and resolves stagnation, and is good at treating liver qi stagnation syndrome, Citrus aurantium regulates qi and relieves fullness, removes stagnation and resolves bloating, Chuanlianzi soothes the liver and releases heat, promotes qi and relieves pain, and the whole prescription has the effects of soothing the liver and relieving depression, harmonizing the stomach and reducing adverse reactions, and promoting qi and resolving nodules. It is used for liver qi stagnation, which turns into heat over time, and evil heat invades the stomach, with symptoms of liver and stomach heat stagnation syndrome; chest yang is not strong, ascending and descending are perverse, clear qi does not rise, turbid yin goes against the flow, phlegm and qi block the chest and diaphragm, and symptoms of qi stagnation and phlegm blockage syndrome.

[0012] The purpose of the present invention is to provide a Chinese medicine composition for treating non-erosive gastroesophageal reflux and a preparation method and application thereof.

[0013] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are particularly adopted:

[0014] In a first aspect, the present invention provides a Chinese medicine composition formula for treating non-erosive gastroesophageal reflux, which is composed of the following components: 2-10 parts of bupleurum, 2-10 parts of curcuma zedoaria, 2-15 parts of white peony root, 2-20 parts of Arcainflata Reeve (shell of Arcainflata Reeve, an animal of the family Arcaidae), 2-20 parts of oyster, 1-10 parts of coptis root, 1-10 parts of pinellia tuber, 2-15 parts of green peel, 2-15 parts of fructus aurantii, 2-10 parts of toosendan fruit, and 2-10 parts of magnolia bark.

[0015] Furthermore, the formula of the Chinese medicine composition consists of the following components in parts by weight: 5 parts of bupleurum, 5 parts of curcuma, 6 parts of white peony root, 8 parts of corrugated stone, 8 parts of oyster, 2 parts of coptis root, 2 parts of pinellia, 6 parts of green peel, 6 parts of aurantium, 5 parts of toosendan fruit, and 5 parts of magnolia bark.

[0016] In a second aspect, the present invention provides a traditional Chinese medicine composition for treating non-erosive gastroesophageal reflux, which is composed of the following components: water extract of bupleurum, white peony root, fructus cordata, coptis chinensis, pinellia ternata, citrus aurantium, fructus ligusticum, magnolia officinalis, zedoaria officinalis, alcohol extract of zedoaria, zedoaria residue and enzymatic extract of oyster.

[0017] Furthermore, the Chinese medicine composition is obtained from the following raw materials in parts by weight: 2-10 parts of bupleurum, 2-10 parts of curcuma, 2-15 parts of white peony root, 2-20 parts of corrugated paper, 2-20 parts of oyster, 1-10 parts of coptis root, 1-10 parts of pinellia tuber, 2-15 parts of green peel, 2-15 parts of fructus aurantii, 2-10 parts of toosendan fruit, and 2-10 parts of magnolia bark.

[0018] Furthermore, the Chinese medicine composition is obtained from the following raw materials in parts by weight: 5 parts of bupleurum, 5 parts of curcuma, 6 parts of white peony root, 8 parts of corrugated stone, 8 parts of oyster, 2 parts of coptis root, 2 parts of pinellia, 6 parts of green peel, 6 parts of aurantium, 5 parts of toosendan fruit, and 5 parts of magnolia bark.

[0019] In a third aspect, the present invention provides a method for preparing a Chinese medicine composition for treating non-erosive gastroesophageal reflux, the preparation method comprising the following steps:

[0020] Bupleurum, white peony root, walnut fruit, coptis root, qingbanxia, ​​qingpi, zhifructus aurantii, chuanlianzi, magnolia officinalis, add water to extract, dry the liquid to obtain bupleurum, white peony root, walnut fruit, coptis root, qingbanxia, ​​qingpi, zhifructus aurantii, chuanlianzi, magnolia officinalis water extract; Wenyujin extract by reflux, dry the liquid to obtain Wenyujin alcohol extract; Wenyujin residue and oyster powder are hydrolyzed by adding water, then boiled for extraction, dry the liquid to obtain Wenyujin residue and oyster enzymatic extract;

[0021] The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit and magnolia bark, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition.

[0022] Furthermore, the specific steps of the preparation method of the Chinese medicine composition are:

[0023] Add 8-12 times the amount of water to the pieces of bupleurum, white peony root, walnut fruit, coptis root, qingbanxia, ​​qingpi, zhizi, chuanlianzi, and magnolia bark, boil for 50-70 minutes, filter, add 6-10 times the amount of water to the residue, boil for 20-40 minutes, filter, concentrate the combined liquid and dry, grind the dry paste and pass through a 60-mesh sieve to obtain bupleurum, white peony root, walnut fruit, coptis root, qingbanxia, ​​qingpi, zhizi, chuanlianzi, and magnolia bark water extract;

[0024] The crude powder of Curcuma aromatica slices was extracted by reflux twice, 7 to 9 times the amount of 85 to 95% ethanol was added for the first time, and the extraction was performed for 50 to 70 minutes, and the extraction was filtered; 6 to 8 times the amount of 85 to 95% ethanol was added for the second time, and the extraction was performed for 50 to 70 minutes, and the extraction was performed. The combined medicinal liquid was concentrated under reduced pressure at 60°C and dried, and the dry paste was crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica alcohol extract;

[0025] The turmeric dregs and oyster powder are extracted with water twice, the first time the amount is 8 to 12 times, the pH value is adjusted to 5.8 to 6.2, 600 to 1000 U of polygalacturonase and 1200 to 1800 U of papain are added per kilogram of the decoction piece, enzymolysis is performed at 38 to 42° C. for 5 to 7 hours, then boiled and extracted for 50 to 70 minutes, centrifuged, the second time the amount is 6 to 10 times, the pH value is adjusted to 5.8 to 6.2, boiled and extracted for 50 to 70 minutes, centrifuged, the combined medicinal solution is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the turmeric dregs and oyster enzymolysis extract is obtained;

[0026] The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit and magnolia bark, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition.

[0027] Furthermore, in a preferred embodiment of the present invention, the preparation method of the Chinese medicine composition comprises the following specific steps:

[0028] Add 10 times the amount of water to the pieces of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae, decoction pieces, and boil for 60 minutes, filter, add 8 times the amount of water to the residue, boil for 30 minutes, filter, concentrate and dry the combined medicinal liquid, grind the dry paste and pass through a 60-mesh sieve to obtain the water extract of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae;

[0029] The coarse powder of Curcuma aromatica slices was refluxed and extracted twice. For the first time, 8 times the amount of 90% ethanol was added, and the extraction was carried out for 60 minutes, and the extraction was filtered. For the second time, 7 times the amount of 90% ethanol was added, and the extraction was carried out for 60 minutes, and the extraction was filtered. The combined medicinal solution was concentrated under reduced pressure at 60°C and dried. The dry paste was crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica alcohol extract.

[0030] The turmeric dregs and oyster powder are extracted with water twice, the first time the amount is 10 times, the pH value is adjusted to 6.0, 800U of polygalacturonase and 1500U of papain are added per kilogram of the slices, enzymolysis is carried out at 40°C for 6 hours, then boiled and extracted for 60 minutes, centrifuged, the second time the amount is 8 times, the pH value is adjusted to 6.0, boiled and extracted for 60 minutes, centrifuged, the combined liquid is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the turmeric dregs and oyster enzymolysis extract are obtained;

[0031] The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit, magnolia officinalis, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition; the auxiliary material dextrin is added to the composition to granulate, dry, granulate and bag to obtain granules.

[0032] In a fourth aspect, the present invention also provides a use of the above-mentioned composition in the preparation of a drug for treating non-erosive gastroesophageal reflux.

[0033] Compared with the prior art, the beneficial effects of the present invention include at least:

[0034] 1. It can select appropriate medicinal ingredients and proportions according to different syndromes of NERD and accurately locate the disease.

[0035] Second, it can regulate gastrointestinal function and blood circulation from multiple levels and pathways to achieve comprehensive and integrated treatment. It can effectively improve symptoms, reduce recurrence, and improve the quality of life.

[0036] 3. No obvious toxic side effects and good safety.

[0037] Fourth, the production method is simple and can be made into pharmaceutically acceptable dosage forms, such as tablets, capsules, granules, etc. Granules are convenient for clinical use, have a large drug loading capacity, and are easy to store and carry.

[0038] 5. Low cost and easy for patients to accept. DETAILED DESCRIPTION

[0039] The embodiments of the present invention will be described in detail below in conjunction with the examples, but it will be appreciated by those skilled in the art that the following examples are only used to illustrate the present invention and should not be construed as limiting the scope of the present invention. If specific conditions are not specified in the examples, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0040] The features and properties of the present invention are further described in detail below in conjunction with the embodiments:

[0041] 1. Composition and preparation method thereof Examples and comparative examples

[0042] Example 1

[0043] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0044] Add 8 times the amount of water to the pieces of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Chuanlian, and Rhizoma Magnoliae, decoction for 70 minutes, filter, add 6 times the amount of water to the residue, decoct for 40 minutes, filter, concentrate and dry the combined medicinal liquid, grind the dry paste and pass through a 60-mesh sieve to obtain the water extract of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Chuanlian, and Rhizoma Magnoliae;

[0045] The crude powder of Curcuma aromatica slices was extracted by reflux twice, 7 times the amount of 95% ethanol was added for the first time, and the extraction was carried out for 50 minutes, and the extraction was filtered; 8 times the amount of 85% ethanol was added for the second time, and the extraction was carried out for 70 minutes, and the extraction was filtered; the combined medicinal solution was concentrated under reduced pressure at 60°C and dried, and the dry paste was crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica alcohol extract;

[0046] The turmeric dregs and oyster powder are extracted with water twice, the first time the amount is 8 times, the pH value is adjusted to 6.2, 600U of polygalacturonase and 1800U of papain are added per kilogram of the slices, enzymolysis is performed at 38°C for 7 hours, then boiled and extracted for 50 minutes, centrifuged, the second time the amount is 10 times, the pH value is adjusted to 5.8, boiled and extracted for 70 minutes, centrifuged, the combined liquid is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the turmeric dregs and oyster enzymolysis extract are obtained;

[0047] The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit, magnolia officinalis, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition; the auxiliary material dextrin is added to the composition to granulate, dry, granulate and bag to obtain granules.

[0048] Example 2

[0049] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0050] Add 12 times the amount of water to the pieces of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae, decoction pieces, and boil for 50 minutes, filter, add 10 times the amount of water to the residue, boil for 20 minutes, filter, concentrate the combined liquid, dry, grind the dry paste and pass through a 60-mesh sieve to obtain the water extract of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae;

[0051] The crude powder of Curcuma aromatica slices was extracted by reflux twice, 9 times the amount of 85% ethanol was added for the first time, and the extraction was performed for 70 minutes, and the extraction was filtered; 6 times the amount of 95% ethanol was added for the second time, and the extraction was performed for 50 minutes, and the extraction was filtered; the combined medicinal solution was concentrated under reduced pressure at 60°C and dried, and the dry paste was crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica alcohol extract;

[0052] The turmeric dregs and oyster powder are extracted with water twice, the first time the amount is 12 times, the pH value is adjusted to 5.8, 1000U of polygalacturonase and 1200U of papain are added per kilogram of the slices, enzymolysis is carried out at 42°C for 5 hours, then boiled and extracted for 70 minutes, centrifuged, the second time the amount is 6 times, the pH value is adjusted to 6.2, boiled and extracted for 50 minutes, centrifuged, the combined liquid is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the turmeric dregs and oyster enzymatic extract are obtained;

[0053] The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit, magnolia officinalis, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition; the auxiliary material dextrin is added to the composition to granulate, dry, granulate and bag to obtain granules.

[0054] Example 3

[0055] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0056] Add 10 times the amount of water to the pieces of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae, decoction pieces, and boil for 60 minutes, filter, add 8 times the amount of water to the residue, boil for 30 minutes, filter, concentrate and dry the combined medicinal liquid, grind the dry paste and pass through a 60-mesh sieve to obtain the water extract of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae;

[0057] The crude powder of Curcuma aromatica slices was extracted by reflux twice, and 8 times the amount of 90% ethanol was added for the first time, and the extraction was carried out for 60 minutes, and the extraction was filtered. The second time, 7 times the amount of 90% ethanol was added, and the extraction was carried out for 60 minutes, and the extraction was filtered. The combined medicinal liquid was concentrated under reduced pressure at 60°C and dried, and the dry paste was crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica alcohol extract;

[0058] The turmeric dregs and oyster powder are extracted with water twice, the first time the amount is 10 times, the pH value is adjusted to 6.0, 800U of polygalacturonase and 1500U of papain are added per kilogram of the slices, enzymolysis is carried out at 40°C for 6 hours, then boiled and extracted for 60 minutes, centrifuged, the second time the amount is 8 times, the pH value is adjusted to 6.0, boiled and extracted for 60 minutes, centrifuged, the combined liquid is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the turmeric dregs and oyster enzymolysis extract are obtained;

[0059] The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit, magnolia officinalis, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition; the auxiliary material dextrin is added to the composition to granulate, dry, granulate and bag to obtain granules.

[0060] Comparative Example 1

[0061] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0062] Take the above-mentioned pieces, add 10 times the amount of water, boil for 60 minutes, filter, add 8 times the amount of water to the residue and boil for 30 minutes, filter, concentrate and dry the combined medicinal liquid, crush the dry paste and pass through a 60-mesh sieve to obtain a water extract;

[0063] The above water extract is added with auxiliary material dextrin for granulation, dried, granulated and bagged to obtain granules.

[0064] Comparative Example 2

[0065] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0066] Take the above-mentioned crude powder of the decoction pieces, reflux extract twice, add 8 times the amount of 90% ethanol for the first time, extract for 60 minutes, filter, add 7 times the amount of 90% ethanol for the second time, extract for 60 minutes, filter, the combined medicinal solution is concentrated under reduced pressure at 60°C and dried, the dry paste is crushed and passed through a 60-mesh sieve to obtain an alcohol extract;

[0067] The above alcohol extract is added with auxiliary material dextrin for granulation, dried, granulated and bagged to obtain granules.

[0068] Comparative Example 3

[0069] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0070] Add 10 times the amount of water to the pieces of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae, decoction pieces, and boil for 60 minutes, filter, add 8 times the amount of water to the residue, boil for 30 minutes, filter, concentrate and dry the combined medicinal liquid, grind the dry paste and pass through a 60-mesh sieve to obtain the water extract of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae;

[0071] Oyster powder, reflux extraction twice, the first time adding 8 times the amount of 90% ethanol, extracting for 60 minutes, filtering, the second time adding 7 times the amount of 90% ethanol, extracting for 60 minutes, filtering, the combined liquid was concentrated under reduced pressure at 60°C and dried, the dry paste was crushed and passed through a 60-mesh sieve to obtain oyster alcohol extract;

[0072] The oyster residue and the coarse powder of Curcuma aromatica slices were extracted with water twice, the first time the amount was 10 times, the pH value was adjusted to 6.0, 800U of polygalacturonase and 1500U of papain were added per kilogram of the slices, and the mixture was hydrolyzed at 40°C for 6 hours, then boiled and extracted for 60 minutes, centrifuged, the second time the amount was 8 times, the pH value was adjusted to 6.0, boiled and extracted for 60 minutes, centrifuged, the combined liquid was concentrated under reduced pressure and dried, the dry paste was crushed and passed through a 60-mesh sieve, and the enzymatic hydrolysis extract of oyster residue and Curcuma aromatica was obtained;

[0073] The above-mentioned water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit, magnolia officinalis, oyster alcohol extract, oyster residue and zedoaria enzymatic extract are mixed to obtain a composition; the auxiliary material dextrin is added to the composition to granulate, dry, granulate and bag to obtain granules.

[0074] Comparative Example 4

[0075] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0076] Add 10 times the amount of water to the pieces of Curcuma wenyujin, White Peony Root, Fructus Aurantii, Coptis chinensis, Pinellia ternata, Pericarpium Citri Reticulatae, Fructus Toosendan, and Magnolia officinalis, decoct for 60 minutes, filter, add 8 times the amount of water to the residue, decoct for 30 minutes, filter, concentrate and dry the combined medicinal liquid, grind the dry paste and pass through a 60-mesh sieve to obtain the water extract of Curcuma wenyujin, White Peony Root, Fructus Aurantii, Coptis chinensis, Pinellia ternatae, Pericarpium Citri Reticulatae, Fructus Toosendan, and Magnolia officinalis;

[0077] The crude powder of Bupleurum slices was refluxed and extracted twice, and 8 times the amount of 90% ethanol was added for the first time, and the extraction was carried out for 60 minutes, and the extraction was filtered. The second time, 7 times the amount of 90% ethanol was added, and the extraction was carried out for 60 minutes, and the extraction was filtered. The combined medicinal solution was concentrated under reduced pressure at 60°C and dried, and the dry paste was crushed and passed through a 60-mesh sieve to obtain Bupleurum alcohol extract;

[0078] The bupleurum residue and oyster powder are extracted with water twice, the first time the amount is 10 times, the pH value is adjusted to 6.0, 800U of polygalacturonase and 1500U of papain are added per kilogram of the slices, enzymolysis is carried out at 40°C for 6 hours, then boiled and extracted for 60 minutes, centrifuged, the second time the amount is 8 times, the pH value is adjusted to 6.0, boiled and extracted for 60 minutes, centrifuged, the combined liquid is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the bupleurum residue and oyster enzymolysis extract is obtained;

[0079] The above-mentioned water extracts of Curcuma aromatica, white peony root, Cortex citri calcaryi, Rhizoma Coptidis, Rhizoma Pinelliae, Pericarpium Citri Reticulatae, Fructus Aurantii Immaturus, Fructus Toosendan, Magnolia officinalis, alcohol extract of Bupleurum chinense, Bupleurum chinense residue and enzymatic extract of Concha Ostreae are mixed to obtain a composition; the auxiliary material dextrin is added to the composition to granulate, dry, granulate and bag to obtain granules.

[0080] Comparative Example 5

[0081] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0082] Add 10 times the amount of water to the pieces of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae, decoction pieces, and boil for 60 minutes, filter, add 8 times the amount of water to the residue, boil for 30 minutes, filter, concentrate and dry the combined medicinal liquid, grind the dry paste and pass through a 60-mesh sieve to obtain the water extract of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae;

[0083] The coarse powder of Curcuma aromatica slices and oyster powder were refluxed and extracted twice, and 8 times the amount of 90% ethanol was added for the first time, and the extraction was carried out for 60 minutes, and the extraction was filtered. The second time, 7 times the amount of 90% ethanol was added, and the extraction was carried out for 60 minutes, and the extraction was filtered. The combined medicinal solution was concentrated under reduced pressure at 60°C and dried, and the dry paste was crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica and oyster alcohol extract;

[0084] The turmeric and oyster residues were extracted with water twice, the first time the amount was 10 times the amount, the pH value was adjusted to 6.0, 800U of polygalacturonase and 1500U of papain were added per kilogram of the slices, and the mixture was hydrolyzed at 40°C for 6 hours, then boiled and extracted for 60 minutes, and centrifuged. The second time the amount was 8 times the amount, the pH value was adjusted to 6.0, the mixture was boiled and extracted for 60 minutes, and centrifuged. The combined medicinal solution was concentrated under reduced pressure and dried, and the dry paste was crushed and passed through a 60-mesh sieve to obtain the enzymatic extract of turmeric and oyster residues;

[0085] The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit, and magnolia officinalis, the alcohol extracts of zedoaria and oyster, and the enzymatic extracts of zedoaria and oyster residues are mixed to obtain a composition; the auxiliary material dextrin is added to the composition to granulate, dry, granulate, and bag to obtain granules.

[0086] Comparative Example 6

[0087] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0088] Add 10 times the amount of water to the pieces of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae, decoction pieces, and boil for 60 minutes, filter, add 8 times the amount of water to the residue, boil for 30 minutes, filter, concentrate and dry the combined medicinal liquid, grind the dry paste and pass through a 60-mesh sieve to obtain the water extract of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae;

[0089] The crude powder of Curcuma aromatica slices was extracted by reflux twice, and 8 times the amount of 90% ethanol was added for the first time, and the extraction was carried out for 60 minutes, and the extraction was filtered. The second time, 7 times the amount of 90% ethanol was added, and the extraction was carried out for 60 minutes, and the extraction was filtered. The combined medicinal liquid was concentrated under reduced pressure at 60°C and dried, and the dry paste was crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica alcohol extract;

[0090] The turmeric dregs and oyster powder are extracted with water twice, the first time the amount is 10 times, the pH value is adjusted to 6.0, 800U of polygalacturonase is added per kilogram of the slices, enzymolysis is performed at 40°C for 6 hours, then boiled and extracted for 60 minutes, centrifuged, the second time the amount is 8 times, the pH value is adjusted to 6.0, boiled and extracted for 60 minutes, centrifuged, the combined liquid is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the turmeric dregs and oyster enzymolysis extract is obtained;

[0091] The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit, magnolia officinalis, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition; the auxiliary material dextrin is added to the composition to granulate, dry, granulate and bag to obtain granules.

[0092] Comparative Example 7

[0093] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0094] Add 10 times the amount of water to the pieces of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae, decoction pieces, and boil for 60 minutes, filter, add 8 times the amount of water to the residue, boil for 30 minutes, filter, concentrate and dry the combined medicinal liquid, grind the dry paste and pass through a 60-mesh sieve to obtain the water extract of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae;

[0095] The crude powder of Curcuma aromatica slices was extracted by reflux twice, and 8 times the amount of 90% ethanol was added for the first time, and the extraction was carried out for 60 minutes, and the extraction was filtered. The second time, 7 times the amount of 90% ethanol was added, and the extraction was carried out for 60 minutes, and the extraction was filtered. The combined medicinal liquid was concentrated under reduced pressure at 60°C and dried, and the dry paste was crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica alcohol extract;

[0096] The turmeric dregs and oyster powder are extracted with water twice, the first time the amount is 10 times, the pH value is adjusted to 6.0, 1500U of papain is added per kilogram of the slices, enzymolysis is performed at 40°C for 6 hours, then boiled and extracted for 60 minutes, centrifuged, the second time the amount is 8 times, the pH value is adjusted to 6.0, boiled and extracted for 60 minutes, centrifuged, the combined liquid is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the turmeric dregs and oyster enzymolysis extract is obtained;

[0097] The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit, magnolia officinalis, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition; the auxiliary material dextrin is added to the composition to granulate, dry, granulate and bag to obtain granules.

[0098] Comparative Example 8

[0099] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0100] Add 10 times the amount of water to the pieces of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae, decoction pieces, and boil for 60 minutes, filter, add 8 times the amount of water to the residue, boil for 30 minutes, filter, concentrate and dry the combined medicinal liquid, grind the dry paste and pass through a 60-mesh sieve to obtain the water extract of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae;

[0101] The crude powder of Curcuma aromatica slices was extracted by reflux twice, and 8 times the amount of 90% ethanol was added for the first time, and the extraction was carried out for 60 minutes, and the extraction was filtered. The second time, 7 times the amount of 90% ethanol was added, and the extraction was carried out for 60 minutes, and the extraction was filtered. The combined medicinal liquid was concentrated under reduced pressure at 60°C and dried, and the dry paste was crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica alcohol extract;

[0102] The turmeric dregs and oyster powder are extracted with water twice, the first time the amount is 10 times, the pH value is adjusted to 6.0, 800U of cellulase and 1500U of papain are added per kilogram of the slices, enzymolysis is performed at 40°C for 6 hours, then boiled and extracted for 60 minutes, centrifuged, the second time the amount is 8 times, the pH value is adjusted to 6.0, boiled and extracted for 60 minutes, centrifuged, the combined liquid is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the turmeric dregs and oyster enzymolysis extract are obtained;

[0103] The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit, magnolia officinalis, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition; the auxiliary material dextrin is added to the composition to granulate, dry, granulate and bag to obtain granules.

[0104] Comparative Example 9

[0105] 50g of Bupleurum, 50g of Curcuma, 60g of White Peony, 80g of Corrugated Seed, 80g of Oyster, 20g of Coptis, 20g of Pinellia, 60g of Citrus aurantium, 60g of Citrus aurantium, 50g of Toosendan, 50g of Magnolia officinalis

[0106] Add 10 times the amount of water to the pieces of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae, decoction pieces, and boil for 60 minutes, filter, add 8 times the amount of water to the residue, boil for 30 minutes, filter, concentrate and dry the combined medicinal liquid, grind the dry paste and pass through a 60-mesh sieve to obtain the water extract of Radix Bupleuri, Radix Paeoniae Alba, Fructus Cordatae, Rhizoma Coptis, Rhizoma Pinelliae, Rhizoma Citri Reticulatae, Fructus Citri Reticulatae, Fructus Toosendan, and Rhizoma Magnoliae;

[0107] The crude powder of Curcuma aromatica slices was extracted by reflux twice, and 8 times the amount of 90% ethanol was added for the first time, and the extraction was carried out for 60 minutes, and the extraction was filtered. The second time, 7 times the amount of 90% ethanol was added, and the extraction was carried out for 60 minutes, and the extraction was filtered. The combined medicinal liquid was concentrated under reduced pressure at 60°C and dried, and the dry paste was crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica alcohol extract;

[0108] The turmeric dregs and oyster powder are extracted with water twice, the first time the amount is 10 times, the pH value is adjusted to 6.0, 800U of polygalacturonase and 1500U of trypsin are added per kilogram of the slices, enzymolysis is carried out at 40°C for 6 hours, then boiled and extracted for 60 minutes, centrifuged, the second time the amount is 8 times, the pH value is adjusted to 6.0, boiled and extracted for 60 minutes, centrifuged, the combined liquid is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the turmeric dregs and oyster enzymatic extract are obtained;

[0109] The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit, magnolia officinalis, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition; the auxiliary material dextrin is added to the composition to granulate, dry, granulate and bag to obtain granules.

[0110] Experimental Example 1

[0111] 1. Model establishment and drug administration

[0112] SPF male SD rats (the number of animals was increased according to the mortality rate of the combined surgical model) were selected, weighing 180-220g and aged 6-8 weeks. After adaptive feeding, 10 rats were randomly selected as the sham operation group according to their body weight. The rats in the sham operation group were sutured after laparotomy, and the rest of the rats were used to construct the combined surgical model. They were fasted for 24 hours before surgery but not water, and anesthetized with intraperitoneal injection of avertin (10mL / kg). The skin below the xiphoid process of the abdomen was prepared for surgery. The animals were placed on the operating table in a supine position, and the chest and abdomen were disinfected with iodine. After the midline incision of the upper abdomen, the cardia muscle was longitudinally incised 0.5cm at the junction of the esophagus and stomach, and separated to the mucosal layer, so that the cardia was relaxed and the pressure was reduced to strengthen gastric reflux. The pylorus was then half-ligated, that is, a glass rod with a diameter of 4mm was placed on the outside of the pylorus of the stomach, and the glass rod and the pylorus were ligated together, avoiding blood vessels. 3-0 non-absorbable sutures were used during suture to prevent the animal from absorbing the ligated part by itself. After ligation, the glass rod was withdrawn to ensure that the rats formed pyloric stenosis after the model was established, but it did not cause obstruction and the inner diameter of the pylorus was uniform. After injecting cefuroxime sodium for injection into the abdominal cavity, the abdomen was closed and the wound was disinfected with iodine. After surgery, the rats were fasted but not watered. The diet, feces and activity of the rats were observed. After 48 hours, they resumed normal diet. One week after surgery, 5% glucose water was added to the drinking water for support. If the rats had normal diet and activity one week after surgery, the model was successfully established.

[0113] After the model was successfully established, the model rats were randomly divided into a model group, an omeprazole enteric-coated capsule group (3.45 mg / kg), Example 1-3 groups and Comparative Example 1-9 groups according to body weight, with 10 rats in each group. The administration was continued by intragastric administration for 14 days, with the omeprazole enteric-coated capsule group receiving a dose of 3.45 mg / kg body weight, the Example 1-3 groups and Comparative Example 1-9 groups receiving a dose of 1000 mg / kg body weight (1 g of the composition granules corresponds to 3 g of the raw medicinal material), and the model group was given an equal amount of 0.5% CMC-Na, and the intragastric administration volume was 0.5 mL / 100 g body weight.

[0114] Before the last administration, rats in each group were fasted but not watered for 12 h. Rats were anesthetized by intraperitoneal injection of 20% urethane at 7 mL / kg body weight. Blood was collected through the abdominal aorta and centrifuged at 3500 r / min for 15 min. The supernatant was collected and stored at -80 °C for later use. 2 cm of esophageal tissue near the stomach end of the lower esophagus was obtained and cut longitudinally; the remaining tissue was stored in a -80 °C refrigerator for subsequent tissue homogenate index detection.

[0115] 2. Observation indicators

[0116] (1) General observation: The body weight, coat color, mental state, degree of oral regurgitation, activity, food intake, water intake, and stool characteristics of the rats in each group were observed.

[0117] (2) Elisa was used to detect the levels of motilin (MTL), substance P (SP), gastrin (GAS), vasoactive intestinal polypeptide (VIP), IL-8, IL-6 and TNF-α in serum and esophageal mucosal tissue homogenate.

[0118] 3. Results

[0119] (1) Effect of the Chinese medicine composition of the present application on the gas level in esophageal tissue and serum of rats in the combined surgical model

[0120] Table 1 Gas levels in esophageal tissue and serum of rats in each group (Mean±SD)

[0121]

[0122] (2) Effect of the Chinese medicine composition of the present application on the level of MTL in the esophageal tissue and serum of rats in the combined surgical model

[0123] Table 2 MTL levels in esophageal tissue and serum of rats in each group (Mean±SD)

[0124]

[0125] (3) Effect of the Chinese medicine composition of the present application on VIP levels in esophageal tissue and serum of rats in the combined surgical model

[0126] Table 3 VIP levels in esophageal tissue and serum of rats in each group (Mean±SD)

[0127]

[0128] (4) Effect of the Chinese medicine composition of the present application on the SP level in esophageal tissue and serum of rats in the combined surgical model

[0129] Table 4 SP levels in esophageal tissue and serum of rats in each group (Mean±SD)

[0130]

[0131] (5) Effect of the Chinese medicine composition of the present application on TNF-α levels in esophageal tissue and serum of rats with combined surgical model

[0132] Table 5 TNF-α levels in esophageal tissue and serum of rats in each group (Mean±SD)

[0133]

[0134] (6) Effect of the Chinese medicine composition of the present application on IL-6 levels in esophageal tissue and serum of rats in the combined surgical model

[0135] Table 6 IL-6 levels in esophageal tissue and serum of rats in each group (Mean±SD)

[0136]

[0137] (7) Effect of the Chinese medicine composition of the present application on IL-8 levels in esophageal tissue and serum of rats in the combined surgical model

[0138] Table 7 IL-8 levels in esophageal tissue and serum of rats in each group (Mean±SD)

[0139]

[0140] Based on the above results, we can draw the following conclusions:

[0141] The Chinese medicine composition of the present application has a therapeutic effect on rats with non-erosive gastroesophageal reflux disease induced by a composite surgical model.

[0142] The links not described in detail in the present invention are all common knowledge that can be selected by ordinary technicians in the field. Although the present invention has been described in detail above with general descriptions and specific implementation schemes, it is obvious to ordinary technicians in the field that some modifications or improvements can be made on the basis of the present invention. Therefore, these modifications or improvements made on the basis of not departing from the spirit of the present invention all belong to the scope of protection claimed by the present invention.

Claims

1. A Chinese medicine composition for treating non-erosive gastroesophageal reflux, characterized in that: The Chinese medicine composition is composed of the following components: 2-10 parts of bupleurum, 2-10 parts of zedoaria, 2-15 parts of white peony root, 2-20 parts of corrugated stone fruit, 2-20 parts of oyster, 1-10 parts of coptis root, 1-10 parts of pinellia tuber, 2-15 parts of green tangerine peel, 2-15 parts of fructus aurantii, 2-10 parts of toosendan fruit, and 2-10 parts of magnolia bark.

2. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition formula consists of the following components in parts by weight: 5 parts of Bupleurum, 5 parts of Curcuma aromatica, 6 parts of White Peony Root, 8 parts of Corrugated Iron Fragrance, 8 parts of Oyster, 2 parts of Coptis chinensis, 2 parts of Pinellia ternata, 6 parts of Citrus aurantium, 6 parts of Citrus aurantium, 5 parts of Toosendan Fruit, and 5 parts of Magnolia officinalis.

3. A Chinese medicine composition for treating non-erosive gastroesophageal reflux, characterized in that: The traditional Chinese medicine composition is composed of the following components: water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green tangerine peel, fructus aurantii, toosendan fruit, magnolia officinalis, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract.

4. The Chinese medicine composition according to claim 3, characterized in that: The traditional Chinese medicine composition is obtained from the following raw materials in parts by weight: 2-10 parts of bupleurum, 2-10 parts of curcuma, 2-15 parts of white peony root, 2-20 parts of corrugated paper, 2-20 parts of oyster, 1-10 parts of coptis root, 1-10 parts of pinellia tuber, 2-15 parts of green peel, 2-15 parts of fructus aurantii, 2-10 parts of toosendan fruit, and 2-10 parts of magnolia bark.

5. The Chinese medicine composition according to claim 3, characterized in that: The Chinese medicine composition is obtained from the following raw materials in parts by weight: 5 parts of Bupleurum, 5 parts of Curcuma aromatica, 6 parts of White Peony Root, 8 parts of Corrugated Iron Fragrance, 8 parts of Oyster, 2 parts of Coptis chinensis, 2 parts of Pinellia ternata, 6 parts of Citrus aurantium, 6 parts of Citrus aurantium, 5 parts of Toosendan Fruit, and 5 parts of Magnolia officinalis.

6. A method for preparing a Chinese medicine composition for treating non-erosive gastroesophageal reflux, characterized in that: The preparation method comprises the following steps: Bupleurum, white peony root, walnut fruit, coptis root, qingbanxia, ​​qingpi, zhifructus aurantii, chuanlianzi, magnolia officinalis, add water to extract, dry the liquid to obtain bupleurum, white peony root, walnut fruit, coptis root, qingbanxia, ​​qingpi, zhifructus aurantii, chuanlianzi, magnolia officinalis water extract; Wenyujin extract by reflux, dry the liquid to obtain Wenyujin alcohol extract; Wenyujin residue and oyster powder are hydrolyzed by adding water, then boiled for extraction, dry the liquid to obtain Wenyujin residue and oyster enzymatic extract; The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit and magnolia bark, the zedoaria alcohol extract, the zedoaria residue and oyster enzymatic extract are mixed to obtain a composition.

7. The method for preparing the Chinese medicine composition according to claim 6, characterized in that: The specific steps of the preparation method are: Add 8 to 12 times the amount of water to the radix bupleuri, white peony root, walnut fruit, coptis root, walnut tuber, green peel, fructus aurantii, toosendan fruit, and magnolia bark slices, boil for 50 to 70 minutes, filter, add 6 to 10 times the amount of water to the residue, boil for 20 to 40 minutes, filter, concentrate and dry the combined medicinal liquid, grind the dry paste and pass through a 60-mesh sieve to obtain radix bupleuri, white peony root, walnut fruit, coptis root, walnut tuber, green peel, fructus aurantii, toosendan fruit, and magnolia bark water extract; The coarse powder of Curcuma aromatica slices is subjected to reflux extraction twice, and 7 to 9 times the amount of 85 to 95% ethanol is added for the first time, and the extraction is carried out for 50 to 70 minutes, and the extraction is filtered; 6 to 8 times the amount of 85 to 95% ethanol is added for the second time, and the extraction is carried out for 50 to 70 minutes, and the extraction is filtered; the combined medicinal liquid is concentrated under reduced pressure at 60° C. and dried, and the dry paste is crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica alcohol extract; The turmeric dregs and oyster powder are extracted with water twice, the first time the amount is 8 to 12 times, the pH value is adjusted to 5.8 to 6.2, 600 to 1000 U of polygalacturonase and 1200 to 1800 U of papain are added per kilogram of the slices, enzymolysis is performed at 38 to 42° C. for 5 to 7 hours, then boiled and extracted for 50 to 70 minutes, centrifuged, the second time the amount is 6 to 10 times, the pH value is adjusted to 5.8 to 6.2, boiled and extracted for 50 to 70 minutes, centrifuged, the combined medicinal solution is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the turmeric dregs and oyster enzymatic extract are obtained; The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit and magnolia bark, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition.

8. The method for preparing the Chinese medicine composition according to claim 7, characterized in that: The specific steps of the preparation method are: The radix bupleuri, white peony root, walnut fruit, coptis root, purpura tuber, tangerine peel, fructus aurantii, ligusticum chuanxiong, and magnolia bark slices are added with 10 times the amount of water, boiled for 60 minutes, filtered, the residue is added with 8 times the amount of water, boiled for 30 minutes, filtered, the combined medicinal liquid is concentrated and dried, the dry paste is crushed and passed through a 60-mesh sieve to obtain radix bupleuri, white peony root, walnut fruit, coptis root, purpura tuber, tangerine peel, fructus aurantii, ligusticum chuanxiong, and magnolia bark water extract; The coarse powder of Curcuma aromatica slices is subjected to reflux extraction twice, wherein 8 times the amount of 90% ethanol is added for the first extraction, the extraction takes place for 60 minutes, and the extraction is filtered; and 7 times the amount of 90% ethanol is added for the second extraction, the extraction takes place for 60 minutes, and the extraction is filtered; the combined medicinal solution is concentrated under reduced pressure at 60° C. and dried, and the dry paste is crushed and passed through a 60-mesh sieve to obtain the Curcuma aromatica alcohol extract.

9. The method for preparing the Chinese medicine composition according to claim 7, characterized in that: The specific steps of the preparation method are: The turmeric dregs and oyster powder are extracted with water twice, the first time the amount is 10 times, the pH value is adjusted to 6.0, 800U of polygalacturonase and 1500U of papain are added per kilogram of the slices, enzymolysis is performed at 40°C for 6 hours, then boiled and extracted for 60 minutes, centrifuged, the second time the amount is 8 times, the pH value is adjusted to 6.0, boiled and extracted for 60 minutes, centrifuged, the combined liquid is concentrated under reduced pressure and dried, the dry paste is crushed and passed through a 60-mesh sieve, and the turmeric dregs and oyster enzymolysis extract are obtained; The water extracts of bupleurum, white peony root, corrugated fruit, coptis root, pinellia tuber, green peel, fructus aurantii, toosendan fruit and magnolia bark, zedoaria alcohol extract, zedoaria residue and oyster enzymatic extract are mixed to obtain a composition.

10. Use of the composition according to any one of claims 3 to 5 in the preparation of a medicament for treating non-erosive gastroesophageal reflux.

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