Application of traditional Chinese medicine composition in preparation of medicine for treating gastroesophageal reflux disease

Abstract

The invention discloses application of a traditional Chinese medicine composition in preparation of a medicine for treating gastroesophageal reflux disease, and belongs to the technical field of biological medicine. The traditional Chinese medicine composition is applied as a main active component, and experiments prove that the traditional Chinese medicine composition can improve rat hair and irritation states to a certain extent, increase the pH value of the joint of gastroesophagus, reduce the levels of inflammatory factors IL-6 and IL-1beta, improve esophageal tissue pathological damage, reduce the number of mast cells and improve the curative effect of the rat. The traditional Chinese medicine composition has an excellent treatment effect on the gastroesophageal reflux disease of rats. The medicine for treating the gastroesophageal reflux disease is definite in medicinal curative effect and low in side effect, and has wide medical application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and specifically relates to an application of a traditional Chinese medicine composition in preparing a medicine for treating gastroesophageal reflux disease. Background Art

[0002] Gastroesophageal reflux disease is a common clinical disease, which refers to a disease in which the contents of the stomach and duodenum reflux into the esophagus or above, reflux into the esophagus, mouth (including throat) or lungs, causing uncomfortable symptoms and / or complications such as heartburn, acid reflux, chest pain, etc.

[0003] However, gastroesophageal reflux usually leads to a decrease in the pH of the esophageal-gastric junction and gastric juice, causing symptoms such as squamous epithelial hyperplasia and certain inflammatory reactions.

[0004] The pyloric ligation combined with cardia muscle incision or tearing rat model is a commonly used model of gastric acid reflux disease. The starting point of pyloric ligation is to limit the emptying of gastric contents, increase the intragastric pressure, and thus make the gastric contents reflux into the esophagus and cause esophageal lesions. The purpose of cardia muscle tearing is to relax the cardia and lack muscle tension. The cardia is the cardia at the lower end of the esophagus. If the cardia is not closed tightly, the acidic solution in the stomach will reflux into the esophagus.

[0005] At present, gastroesophageal reflux disease seriously affects the quality of life of patients. Currently, the first choice of Western medicine treatment is acid suppression therapy with proton pump inhibitors (PPI) and potassium ion competitive acid blockers (P-CAB), as well as H2 receptor antagonists, gastrointestinal prokinetic drugs and other drugs. However, the above Western medicine treatment has poor effects, easy recurrence after discontinuation of medication, poor patient compliance, and adverse reactions, which affect the quality of life of patients. Summary of the invention

[0006] The purpose of the present invention is to provide an application of a traditional Chinese medicine composition in the preparation of a drug for treating gastroesophageal reflux disease. The traditional Chinese medicine composition is used as a main active ingredient. Experiments have shown that the traditional Chinese medicine composition can improve the hair and irritability of rats to a certain extent, increase the pH value at the gastroesophageal junction, reduce the levels of inflammatory factors IL-6 and IL-1β, improve esophageal tissue pathological damage, reduce the number of mast cells, and can play an excellent therapeutic role in gastroesophageal reflux disease in rats.

[0007] The present invention is achieved through the following technical solutions:

[0008] A use of a Chinese medicine composition in preparing a drug for treating gastroesophageal reflux disease, wherein the Chinese medicine preparation is prepared from bupleurum, white peony root, bran-fried immature bitter orange, ginger pinellia, cuttlebone, bletilla striata, kudzu root, notoginseng and liquorice;

[0009] The preparation method is:

[0010] Bupleurum, white peony root, bran-fried immature bitter orange, ginger pinellia, cuttlebone, bletilla striata, kudzu root, notoginseng and liquorice are selected and mixed according to corresponding weight parts, and after water extraction, the Chinese medicine stock solution is filtered to obtain the Chinese medicine stock solution, and spray drying is adopted to obtain the Chinese medicine composition;

[0011] Or, selecting radix bupleuri, white peony root, stir-fried immature bitter orange, radix puerariae and notoginseng according to corresponding weight parts, mixing them, and extracting them with alcohol at a weight fraction of 30-70% to obtain an alcohol extract and alcohol-extracted medicinal residues;

[0012] Selecting Pinellia ternata, Cuttlebone, Licorice, Bletilla striata and the alcohol-extracted drug residues according to corresponding weight parts, mixing them, and extracting with water to obtain a water extract;

[0013] After the alcohol extract and the water extract are mixed, spray drying is adopted to obtain a traditional Chinese medicine composition.

[0014] Preferably, the Chinese medicine preparation is composed of the following raw materials in parts by weight:

[0015] 1-15 parts of bupleurum, 2-20 parts of white peony root, 1-15 parts of stir-fried aurantium immature with bran, 1-12 parts of pinellia ternata, 2-15 parts of cuttlebone, 2-20 parts of bletilla striata, 2-19 parts of kudzu root, 1-12 parts of panax notoginseng, and 1-15 parts of liquorice.

[0016] Preferably, the drug is used to increase body weight, improve coat gloss, improve irritability, increase gastric juice pH, increase gastroesophageal junction pH, reduce levels of inflammatory factors IL-6 and IL-1β, improve esophageal tissue pathological damage, and reduce the number of mast cells.

[0017] Preferably, the pathological damage refers to esophageal mucosal epithelial hyperplasia, mucosal lamina propria papillary protrusions and inflammatory cell infiltration.

[0018] A medicine for treating gastroesophageal reflux disease, wherein the medicine uses the traditional Chinese medicine composition prepared by the preparation method as an active ingredient.

[0019] Preferably, the drug also contains pharmaceutically acceptable excipients to prepare a pharmaceutically corresponding dosage form.

[0020] Preferably, the auxiliary material includes any one of dextrin, mannitol, medicinal starch and microcrystalline cellulose.

[0021] Preferably, the dextrin is maltodextrin.

[0022] Preferably, the dosage form includes any one of a liquid dosage form, a solid dosage form and a semisolid dosage form.

[0023] Preferably, the liquid dosage form includes solutions and / or injections; the solid dosage form includes powders, tablets or granular preparations; and the semisolid dosage form includes suppositories and / or pastes.

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

[0025] The present invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for treating gastroesophageal reflux disease. The traditional Chinese medicine composition is applied as a main active ingredient, and experiments have verified that the traditional Chinese medicine composition can improve the hair and irritability state of rats to a certain extent, increase the pH value at the gastroesophageal junction, reduce the levels of inflammatory factors IL-6 and IL-1β, improve esophageal tissue pathological damage, reduce the number of mast cells, and can play an excellent therapeutic effect on gastroesophageal reflux disease in rats.

[0026] The drug for treating gastroesophageal reflux disease has definite medicinal efficacy, low side effects and has broad medical application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Schematic diagram of HE staining of esophageal tissue; Notes in the figure: green arrows point to the infiltration of inflammatory cells, yellow arrows point to the papillary protrusions of the mucosal lamina propria, and blue arrows point to the proliferation of basal cells;

[0028] Figure 2 Schematic diagram of mast cell staining in esophageal tissue; Note: red arrows point to mast cells. DETAILED DESCRIPTION

[0029] The embodiments of the present invention will be described in detail below in conjunction with examples. However, those skilled in the art will understand 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. The specific conditions not specified in the examples are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially.

[0030] Example:

[0031] Weigh each raw material of the Chinese medicine composition, add ethanol solution or water as shown in the table below, extract (decoction, filtration) to obtain the medicine juice to obtain the Chinese medicine composition, spray dry to obtain medicine powder.

[0032] A traditional Chinese medicine composition for treating gastroesophageal reflux disease is prepared from 300g of bupleurum, 300g of white peony root, 300g of stir-fried immature bitter orange, 300g of ginger pinellia, 300g of kudzu root, 100g of notoginseng, 300g of bletilla striata, 100g of cuttlebone and 200g of liquorice.

[0033] Table 1 Extraction and preparation process of Chinese medicine composition

[0034]

[0035]

[0036] The above-mentioned water extraction and alcohol extraction processes are carried out according to conventional extraction procedures.

[0037] Test example:

[0038] 1. Test materials

[0039] 1.1 Test substances

[0040] The medicinal powders of the five embodiments in the above-mentioned embodiments are as follows: the crude drug content of Example 1 is 10.906 g of crude drug / g; the crude drug content of Example 2 is 13.289 g of crude drug / g; the crude drug content of Example 3 is 12.164 g of crude drug / g; the crude drug content of Example 4 is 17.687 g of crude drug / g, and the crude drug content of Example 5 is 14.126 g of crude drug / g.

[0041] Comparative example: Omeprazole enteric-coated capsules, content 20 mg / capsule, Jinan Mingxin Pharmaceutical, batch number 22091012.

[0042] 1.2 Experimental animals

[0043] SPF SD rats, weighing 180-220 g, half male and half female, certificate number: 110322230100445562. Provided by Beijing Huafukang Biotechnology Co., Ltd., animal license number: SCXK (Beijing) 2019-0008.

[0044] 1.3 Experimental reagents

[0045] Rat IL-6 ELISA kit (cat#88-50625-22; Invitrogen, Carlsbad, CA), rat IL-1β ELISA kit (cat#88-6010-22; Invitrogen, Carlsbad, CA), 2,2,2-tribromoethanol (CAS: 75-80-9, TCI), tert-amyl alcohol (CAS: 75-85-4, MACKLIN)

[0046] 1.4 Experimental equipment

[0047] Freezing centrifuge (micro21R, Thermo Fisher, USA), pH meter (Ohmega, MMS, Netherlands), microplate reader (SPARK, TECAN, Switzerland), electronic balance (MS205DU, Mettler Toledo Co., Ltd., China), electronic balance (JJ323BF, Shuangjie Testing Instrument Factory, Changshu, China), tissue grinder (KZ-5F-3D, Wuhan Sewell Biotechnology Co., Ltd.), pathology section scanner (Pannoramic MIDI, 3DHISTECHLTD, Hungary), pathology section machine (R2235, Leica Instrument Co., Ltd.), embedding machine (EG1150H, Leica, Germany).

[0048] 2. Experimental Methods

[0049] 2.1 Preparation of animal model and drug administration

[0050] The modeling method of pyloric semi-ligation combined with cardia muscle tear was used to replicate the surgical model of gastroesophageal reflux disease. The rats were fasted but not watered for 24 hours before the operation. After anesthesia, the rats were cut longitudinally along the midline of the abdomen, the hepatogastric ligament and the fascia around the stomach were cut, and the stomach was completely lifted out to fully expose the stomach and pylorus. A metal rod with a diameter of 4 mm was placed outside the pylorus of the stomach. The metal rod and the pylorus were ligated together with 4-0 nylon thread, avoiding blood vessels. After the ligation, the metal rod was pulled out 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. The left gastric artery was ligated to prevent bleeding caused by damage to the blood vessels. Blunt separation was performed upward from the esophageal-gastric junction, with a length of about 1 cm, to avoid damage to the esophageal lining. The abdominal cavity was moistened with antibiotics and saline to prevent adhesion. The abdomen was closed after the operation.

[0051] The rats were kept in solitary cages after surgery and were fasted but not deprived of water for 24 hours. A small amount of food was given one day after surgery. After 2-3 days of observation, if there was no abdominal bleeding or mental depression, the model rats were combined into six per cage and fed a normal diet.

[0052] The model rats were randomly divided into 8 groups according to their body weight, namely, sham operation group, model group, omeprazole group, Example 1, Example 2, Example 3, Example 4 and Example 5 groups of the present composition, with 10 rats in each group, half of which were male and half were female. 1 ml was administered per 100 g of rat body weight, and the administration was carried out by gavage for 28 days. Rats in the sham operation group and the model group were gavaged with normal saline, and the drug dosage of the other groups was converted to its equivalent dose with reference to the intended clinical dosage.

[0053] 2.2 General physiological condition and weight observation

[0054] Observe the general physiological conditions of the rats (hair, behavioral status, feces characteristics, etc.), compare the differences between the model group and the normal control group, and the improvement effect after drug treatment. Record the body weight of the rats before and after drug administration.

[0055] 2.3 Monitoring of the esophageal gastric junction and gastric pH

[0056] The rats were anesthetized after fasting for 12 hours, and a pH meter was used to place a detection catheter at the gastroesophageal junction of the rats to detect the pH value about 1 cm above the esophageal-gastric junction. The catheter was then passed through the narrow part of the junction and moved down about 3 cm into the stomach to detect the intragastric pH value.

[0057] 2.4ELISA to detect IL-1β and IL-6 expression levels in tissues

[0058] 2.4.1 Preparation of rat esophageal tissue homogenate

[0059] Rats were dissected, blood was collected from the abdominal aorta, and the stomach and the upper esophagus were removed, rinsed with saline, and excess water was absorbed with filter paper. The esophagus was cut from 1 cm above the gastroesophageal junction, and 20 mg (0.020 g) of esophageal tissue was accurately weighed, 180 μL of 0.9% saline was added, the tissue was chopped and added with grinding magnetic beads, and ground with a tissue grinder. The prepared tissue homogenate was centrifuged at 2500 rpm / min for 10 min, and the supernatant was taken for detection.

[0060] 2.4.2 Detect the concentration of IL-1β and IL-6 in the sample according to the instructions of the ELISA test kit

[0061] The following kits were used for detection:

[0062] ① Prepare the standard sample according to the instructions, make a standard curve with 8 concentration points, and add 100 μL / well of each sample; ② Add 100 μL / well of Assay Buffer A (1X) or ELISA / ELISPOT Diluent (1X) to the blank wells. Add 50 μL / well Assay Buffer A (1X) and 50 μL / well sample to the sample wells, add 50 μL / well Detection Antibody (IL-6) or 100 μL / well sample (IL-1β) to all wells; ③ Seal the plate and incubate at room temperature for 2 hours; ④ Discard the liquid in the plate and wash with 400 μL / well Wash Buffer, allow soaking time (1 minute) in each washing step, and repeat the wash 6 times in total; ⑤ Add 100 μL / well diluted Detection Antibody (IL-1β) to all wells and incubate at room temperature for 1 hour, discard the liquid and wash 5 times (IL-1β); ⑥ Add 100 μL / well HRP to all wells, seal, and incubate at room temperature in the dark for 1 hour; ⑦ Discard the liquid and repeat the wash 6 times; ⑧ Add 100 μL / well 1X TMB. Seal and incubate at room temperature in the dark for 15 minutes; ⑨ Add 100 μL stop solution to each well; ⑩ Detect the absorbance at 450 nm and analyze the data.

[0063] 2.5 HE staining of esophageal tissue

[0064] ① Dewaxing: Take the prepared paraffin sections of esophageal tissue, soak them in xylene solution Ⅰ and Ⅱ for 10 minutes each under a fume hood, then soak them in 90% ethanol for 3 minutes, then put them in 75% and 50% ethanol for 3 minutes each, and soak them in pure water for 2 minutes; ② Hematoxylin staining: soak them in hematoxylin staining solution for 8 minutes, and wash the floating color with pure water; ③ Differentiation with color separation solution for 10 seconds, rinse with pure water for 1 minute; ④ Stain with anti-blue solution for 15 seconds, and rinse with running water for 2 minutes; ⑤ Dehydration: soak them in 85% ethanol for 3 minutes, and soak them in 95% ethanol for 3 minutes; ⑥ Eosin staining: soak them in eosin staining solution for 2 minutes; ⑦ Dehydration and sealing: The sections are placed in anhydrous ethanol Ⅰ, Ⅱ, and Ⅲ for 10 minutes respectively, and then soaked in xylene Ⅰ and Ⅱ in a fume hood for 5 minutes each. Neutral gum is added to the center of the section. After the xylene evaporates, slowly cover the section with a cover glass.

[0065] 2.6 Esophageal mast cell staining

[0066] ① Dewaxing: Take the prepared paraffin sections of esophageal tissue, soak them in xylene solutions Ⅰ and Ⅱ for 10 minutes each, then soak them in 90% ethanol for 3 minutes, then put them in 75% and 50% ethanol for 3 minutes each, and soak them in pure water for 2 minutes; ② Toluidine blue staining: soak them in toluidine blue dye solution for 8 minutes, and wash the floating color with pure water; ③ Differentiation with color separation solution: differentiate them in differentiation solution until mast cells appear blue-purple under light microscope, and stop differentiation by washing with running water; ④ Drying: Place the sections in a 60℃ oven for drying; ⑤ Transparent sealing: Soak them in xylene Ⅰ and Ⅱ in a fume hood for 5 minutes each, add neutral gum in the middle of the section, wait for the xylene to evaporate, and slowly cover the section with a coverslip; ⑥ Collect images for analysis.

[0067] 3. Experimental results

[0068] 3.1 General physiological condition and body weight of rats

[0069] Before surgery, the rats' appearance, weight, behavior and other general conditions were normal. After surgery, the model group rats' hair fell off easily, their fur became dull, and their spirits became apathetic. After the wounds recovered and they began to eat normally and receive drug intervention, the model group rats' fur became dull, their weight increased slowly, and they easily jumped out of their cages and became irritable.

[0070] Compared with the model group, the fur color and luster of the rats in the omeprazole treatment group were obvious, and the irritability was improved; the hair loss phenomenon of the rats in the different embodiment groups of the present composition still existed, and the fur color and irritability were improved to a certain extent. As time went on, the weight of the rats in each group increased, but the increase degree was not statistically significant compared with the model group.

[0071] Table 2 Body weight of rats on days 1, 7, 14 and 28 ( n=10)

[0072]

[0073] 3.2 Esophagogastric junction and gastric pH

[0074] The gastric pH value of rats in each group was detected. Compared with the sham operation group, the gastric pH value of rats in the model group (p<0.05) and the omeprazole treatment group (p<0.01) increased. The gastric pH value of the group treated with Example 1 of the present composition increased significantly (p<0.01), and the gastric pH of Examples 2, 3, and 5 also increased (p<0.05). No significant change was observed in Example 4, as shown in Table 3.

[0075] The pH value of the gastroesophageal junction of each group of rats was detected. After statistics, it was found that compared with the sham operation group, the pH value of the gastroesophageal junction of the rats in the model group was significantly decreased (p<0.05). After treatment with omeprazole, the pH value of the gastroesophageal junction of the rats was significantly increased (p<0.01). After treatment with the five examples of the drug of the present composition, the pH value of the gastroesophageal junction of the rats in each group was significantly increased and the effect was similar (p<0.01), as shown in Table 3.

[0076] Table 3 Rat gastric pH and gastroesophageal junction pH ( n=10)

[0077] Group Gastric pH Gastroesophageal junction pH Sham operation group 4.08±0.58 6.73±0.31 Model Group <![CDATA[3.42±0.54 * ]]> <![CDATA[6.38±0.23 ** ]]> Example 1 Group <![CDATA[4.83±0.50 ## ]]> <![CDATA[7.21±0.24 ## ]]> Example 2 Group <![CDATA[3.97±0.49 # ]]> <![CDATA[7.18±0.25 ## ]]> Example 3 Group <![CDATA[3.96±0.35 # ]]> <![CDATA[6.98±0.23 ## ]]> Example 4 Group 3.34±0.40 <![CDATA[7.20±0.20 ## ]]> Example 5 Group <![CDATA[4.02±0.40 # ]]> <![CDATA[7.06±0.17 ## ]]> Omeprazole group <![CDATA[4.33±0.63 ## ]]> <![CDATA[6.70±0.14 # ]]>

[0078] Note: Compared with sham operation * p<0.05, ** p<0.01, compared with the model group # p<0.05, ## p<0.01.

[0079] 3.3 Expression levels of IL-1β and IL-6 in tissues

[0080] 3.3.1 IL-1β expression level in esophageal tissue

[0081] The expression level of IL-1β in the esophagus of rats in each group was detected. Compared with the sham operation group, the expression of IL-1β in the model group rats was significantly increased (p<0.01). Compared with the model group, the expression level of IL-1β was significantly reduced after omeprazole treatment (p<0.01); the five embodiments of the composition had different degrees of influence on the expression level of IL-1β, among which, embodiment 1, embodiment 4 and embodiment 5 could significantly reduce the expression level of IL-1β (p<0.01), and embodiment 2 and embodiment 3 also had the same effect (p<0.05), but the therapeutic effect was weaker than that of embodiment 1, embodiment 4 and embodiment 5, as shown in Table 4.

[0082] 3.3.2 IL-6 expression level in esophageal tissue

[0083] The IL-6 expression level in the esophageal homogenate of each group of rats was detected. After statistics, it was found that compared with the sham operation group, the IL-6 expression level in the stomach of the model group rats was significantly increased (p<0.01). After drug treatment, the IL-6 expression level in the omeprazole group, Example 1 of the present composition, and Example 4 groups was significantly decreased (p<0.05). The Example 2, Example 3 and Example 5 treatment groups of the present composition were also able to reduce the IL-6 expression level, but the data did not show significance (p>0.05), as shown in Table 5.

[0084] The results in Table 5 and Table 6 show that the composition can reduce the expression levels of IL-6 and IL-1β in the esophagus of rats with non-erosive gastroesophageal reflux, thereby exerting a therapeutic effect, among which Example 1 and Example 4 are better than Example 2, Example 3, and Example 5.

[0085] Table 4 IL-1β and inhibition rate in esophageal tissue homogenate samples ( n=10)

[0086] Group IL-1β (pg / g) Inhibition rate (%) Sham operation group 1417.27±449.19 —— Model Group <![CDATA[1873.79±131.15 * ]]> —— Example 1 <![CDATA[1380.98±307.73 ## ]]> 26.30 Example 2 <![CDATA[1625.94±240.27 # ]]> 13.23 Example 3 <![CDATA[1654.92±277.14 # ]]> 11.68 Example 4 <![CDATA[1567.71±162.27 ## ]]> 16.33 Example 5 <![CDATA[1506.65±197.82 ## ]]> 19.59 Omeprazole group <![CDATA[1349.93±382.47 ## ]]> 27.96

[0087] Note: Compared with sham operation * p<0.05, compared with the model group # p<0.05, ## p<0.01.

[0088] Table 5 IL-6 and inhibition rate in esophageal tissue homogenate samples ( n=10)

[0089]

[0090]

[0091] Note: Compared with sham operation ** p<0.01, compared with the model group # p<0.05.

[0092] 3.4 HE staining of esophageal tissue

[0093] like Figure 1 Figure 1 shows the schematic diagram of HE staining of esophageal tissue. Notes in the figure: The green arrow points to the infiltration of inflammatory cells, the yellow arrow points to the papillary protrusions of the lamina propria of the mucosa, and the blue arrow points to the proliferation of basal cells.

[0094] through Figure 1 HE staining showed that there was no obvious inflammatory reaction in the esophageal tissue of the rats in the sham operation group, and a small number of inflammatory cells were occasionally seen in the epithelial cell layer. After drug administration, compared with the model group, the pathological damage such as squamous epithelial hyperplasia and inflammatory infiltration in the esophageal tissue of the rats in the omeprazole group was significantly alleviated, and the five embodiments of the composition were able to reduce the above pathological damage, among which the effects of reducing damage in embodiment 1, embodiment 4, and embodiment 5 were more obvious.

[0095] 3.5 Staining of mast cells in esophageal tissue

[0096] like Figure 2 Shown is a schematic diagram of mast cell staining in esophageal tissue. Note in the figure: the red arrow points to the mast cell.

[0097] Figure 2Combined with Table 6, it can be seen that compared with the sham operation group, the number of mast cells in the model group increased significantly (p<0.01). Compared with the model group, the number of mast cells decreased significantly after omeprazole treatment (p<0.01), and the number of mast cells in each example group decreased; the number of mast cells in Example 2 and Example 3 decreased (p<0.05), and the number of mast cells in Example 1, Example 4 and Example 5 decreased significantly (p<0.01).

[0098] Table 6 The number of mast cells in esophageal tissue and the rate of mast cell reduction

[0099]

[0100]

[0101] Note: Compared with sham operation ** p<0.01, compared with the model group # p<0.05, ## p<0.01.

[0102] 4 Test results:

[0103] 4.1 After the pyloric hemiligation and cardia muscle tearing surgery, the rats had dull fur color, large changes in weight, and were prone to jumping out of the cage and showing irritability; after treatment with omeprazole, the rats had obvious fur color luster, increased weight, and improved irritability. After treatment with different embodiments of the present composition, the hair loss phenomenon of the rats still existed, the fur color luster was improved to a certain extent, the irritability was improved to a certain extent, and the weight was increased.

[0104] 4.2 In addition, the composition can increase the pH value of the esophageal gastric junction and gastric juice in rats. The five example administration groups have similar effects on the pH value of the gastroesophageal junction, and for the pH in the stomach of rats, Example 1, Example 2, Example 3, and Example 5 can all increase the pH in the stomach (p < 0.05), among which Example 1 has a more significant effect on the pH in the stomach, while Example 2 and Example 3 are less than Example 1 and have similar effects.

[0105] 4.3 Examples 1, 4 and 5 of the present composition can significantly reduce the IL-6 level in the esophageal tissue of rats, and the five examples of the present composition can all reduce the IL-1β level in the esophageal tissue of rats, among which Examples 1 and 4 are significantly better than Examples 2, 3 and 5.

[0106] 4.4HE staining observation of tissue, model group showed obvious pathological damage such as squamous epithelial hyperplasia, inflammatory cell infiltration, etc., indicating that the model was successful. After drug treatment, compared with the model group, the pathological damage such as squamous epithelial hyperplasia and inflammatory infiltration of esophageal tissue in rats in the omeprazole group was significantly alleviated, and the five examples of the composition were able to reduce the above pathological damage, among which, the effect of reducing damage in Example 1, Example 4, and Example 5 was more obvious.

[0107] 4.5 Toluidine blue staining was used to observe mast cells in esophageal tissues. The model group had a larger number of mast cells. Compared with the model group, the omeprazole group and each example group of the present composition could significantly reduce the number of mast cells, among which the effects of Example 1, Example 4 and Example 5 were more significant.

[0108] In summary: There are certain differences in the therapeutic effects between different embodiment groups of the composition, but all of them can improve the hair and irritability state of rats to a certain extent, increase the pH value at the gastroesophageal junction, reduce the levels of inflammatory factors IL-6 and IL-1β, improve esophageal tissue pathological damage, and can play a therapeutic role in gastroesophageal reflux disease in rats.

[0109] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the protection scope of the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. Use of a Chinese medicine composition in preparing a drug for treating gastroesophageal reflux disease, characterized in that: The Chinese medicine preparation is prepared from bupleurum root, white peony root, bran-fried immature bitter orange, ginger pinellia, cuttlebone, bletilla striata, kudzu root, notoginseng and liquorice; The preparation method is: Bupleurum, white peony root, bran-fried immature bitter orange, ginger pinellia, cuttlebone, bletilla striata, kudzu root, notoginseng and liquorice are selected and mixed according to corresponding weight parts, and after water extraction, the Chinese medicine stock solution is filtered to obtain the Chinese medicine stock solution, and spray drying is adopted to obtain the Chinese medicine composition; Or, selecting radix bupleuri, white peony root, stir-fried immature bitter orange, radix puerariae and notoginseng according to corresponding weight parts, mixing them, and extracting them with alcohol at a weight fraction of 30-70% to obtain an alcohol extract and alcohol-extracted medicinal residues; Selecting Pinellia ternata, Cuttlebone, Licorice, Bletilla striata and the alcohol-extracted drug residues according to corresponding weight parts, mixing them, extracting with water, and obtaining a water extract; After the alcohol extract and the water extract are mixed, spray drying is adopted to obtain a traditional Chinese medicine composition.

2. Use of a Chinese medicine composition according to claim 1 in preparing a drug for treating gastroesophageal reflux disease, characterized in that: The Chinese medicine preparation is composed of the following raw materials in parts by weight: 1-15 parts of bupleurum, 2-20 parts of white peony root, 1-15 parts of stir-fried immature bitter orange, 1-12 parts of ginger pinellia, 2-15 parts of cuttlebone, 2-20 parts of bletilla, 2-19 parts of kudzu root, 1-12 parts of panax notoginseng, and 1-15 parts of liquorice.

3. Use of a Chinese medicine composition according to claim 1 in preparing a drug for treating gastroesophageal reflux disease, characterized in that: The drug is used in increasing body weight, improving coat gloss, improving irritability, increasing gastric juice pH, increasing gastroesophageal junction pH, reducing levels of inflammatory factors IL-6 and IL-1β, improving esophageal tissue pathological damage, and reducing the number of mast cells.

4. Use of a Chinese medicine composition according to claim 3 in preparing a drug for treating gastroesophageal reflux disease, characterized in that: The pathological damage refers to esophageal mucosal epithelial hyperplasia, mucosal lamina propria papillary protrusions and inflammatory cell infiltration.

5. A drug for treating gastroesophageal reflux disease, characterized in that: The medicine is a Chinese medicine composition prepared by the preparation method as claimed in claim 1 as an active ingredient.

6. A drug for treating gastroesophageal reflux disease according to claim 5, characterized in that: The medicine also contains pharmaceutically acceptable excipients to prepare pharmaceutically corresponding dosage forms.

7. A drug for treating gastroesophageal reflux disease according to claim 6, characterized in that: The auxiliary material includes any one of dextrin, mannitol, medicinal starch and microcrystalline cellulose.

8. The drug for treating gastroesophageal reflux disease according to claim 7, characterized in that: The dextrin is maltodextrin.

9. The drug for treating gastroesophageal reflux disease according to claim 6, characterized in that: The dosage form includes any one of a liquid dosage form, a solid dosage form and a semisolid dosage form.

10. The drug for treating gastroesophageal reflux disease according to claim 9, characterized in that: The liquid dosage forms include solutions and / or injections; the solid dosage forms include powders, tablets or granular preparations; and the semisolid dosage forms include suppositories and / or pastes.

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