Traditional Chinese medicine composition for treating non-erosive reflux disease and application

Abstract

The invention discloses a traditional Chinese medicine composition for treating non-erosive reflux disease and application, and belongs to the field of biological medicine. The traditional Chinese medicine composition (a formula for clearing heat and calming adverse-rising energy) provided by the invention comprises the following components: persimmon calyx, clove, immature bitter orange, raw bighead atractylodes rhizome, radix bupleuri, codonopsis pilosula, ginger processed pinellia, scutellaria baicalensis, honey-fried licorice root, eupatorium, fried cassia seed and calcined concha arcae. Clinical experiment results show that the traditional Chinese medicine composition provided by the invention improves the clinical symptoms of reflux, heartburn and the like of a patient by clearing heat, eliminating dampness, harmonizing the stomach, calming adverse-rising energy, promoting qi circulation and relaxing bowels, improves the motion function of the esophagus, changes the ultrastructure of esophageal nerve fiber synaptic vesicles of the patient, reduces the number of SP and CGRP positive nerve fibers, changes the average optical density value of the positive nerve fibers, and improves the curative effect of the esophageal nerve fiber synaptic vesicles. Compared with traditional western medicines, the traditional Chinese medicine composition is small in side effect and safe to use. The invention provides a special prescription which is clear in mechanism and outstanding in curative effect for patients suffering from spleen and stomach damp-heat type non-erosive reflux disease.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, and in particular to a traditional Chinese medicine composition and its application for treating non-erosive reflux disease. Background Technology

[0002] Nonerosive reflux disease (NERD) is a common subtype of gastroesophageal reflux disease (GERD). It is a chronic disease caused by multiple factors, with a long course and high recurrence rate; its incidence is reported to be 57%-90%. This disease is closely related to psychological state, causing significant suffering for patients. Although it rarely poses a life-threatening risk, it severely impacts patients' quality of life. Clinical diagnosis is relatively difficult due to the absence of endoscopic esophageal mucosal damage. The main clinical treatment involves long-term use of proton pump inhibitors (PPIs) and prokinetic drugs to relieve symptoms. Many NERD patients experience anxiety and depression, leading to unsatisfactory treatment responses to PPIs; furthermore, anxiety and depression exacerbate reflux symptoms. The annual medical costs for NERD treatment are substantial. Therefore, finding a scientific and effective treatment method and studying its mechanism of action is of significant medical and social importance.

[0003] Existing research indicates that the pathogenesis of NERD is closely related to visceral hypersensitivity mechanisms, which may be associated with overexpression of substance P (SP) and calcitonin gene-related peptide (CGRP). Furthermore, knockout of the transient receptor potential vanilloid (TRPV1) gene has been found to significantly inhibit mechanosensitivity of gastrointestinal afferent nerves induced by distending stimulation. Activated TRPV1 promotes the release of excitatory neurotransmitters CGRP and SP, leading to enhanced gastrointestinal visceral sensitivity. Protein kinase A (PKA) can directly activate TRPV1 and is its upstream regulator.

[0004] In recent years, Traditional Chinese Medicine (TCM) has achieved satisfactory clinical results in treating NERD by applying the theory of syndrome differentiation and treatment, particularly in improving symptoms and reducing recurrence rates. However, it is undeniable that TCM treatment for NERD still has many shortcomings. For example, while TCM has achieved definite clinical efficacy, its specific mechanisms of action remain poorly understood, and standardized TCM compound preparations for clinical application are lacking. In clinical practice, there is a lack of a specific formula and drug with a clear mechanism and definite efficacy for NERD patients with spleen and stomach damp-heat type. Therefore, developing a TCM compound preparation based on TCM theory, capable of clearly targeting modern medical mechanisms, and effective in treating spleen and stomach damp-heat type NERD has significant clinical and social value. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine composition and its application for treating non-erosive reflux disease (NERD), thereby solving the problems existing in the prior art. This invention provides a traditional Chinese medicine compound preparation, "Qingre Jiangni Fang," which clarifies its mechanism of action by regulating the PKA / TRPV1 signaling pathway to affect the visceral hypersensitivity of NERD. At the same time, it improves the ultrastructure of esophageal nerve fiber synaptic vesicles, reduces the number of SP and CGRP positive nerve fibers, and achieves a scientific and effective treatment for spleen and stomach damp-heat type NERD. This makes up for the shortcomings of simple Western medicine treatment, reduces treatment costs and adverse reactions, and provides a new scientific treatment plan for clinical practice.

[0006] To achieve the above objectives, the present invention provides the following solution:

[0007] This invention provides a traditional Chinese medicine composition comprising the following components: persimmon calyx, clove, immature bitter orange, raw atractylodes macrocephala, bupleurum, codonopsis, ginger-processed pinellia, scutellaria baicalensis, prepared licorice root, eupatorium fortunei, stir-fried cassia seed, and calcined oyster shell.

[0008] Further, by weight, it includes the following components: 10 parts persimmon calyx, 5 parts clove, 15 parts immature bitter orange, 20 parts raw atractylodes macrocephala, 9 parts bupleurum, 10 parts codonopsis, 9 parts ginger-processed pinellia, 9 parts scutellaria, 6 parts prepared licorice, 12 parts eupatorium, 30 parts stir-fried cassia seed and 20 parts calcined oyster shell.

[0009] The present invention also provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of a drug for treating gastroesophageal reflux disease.

[0010] Furthermore, the gastroesophageal reflux disease is non-erosive reflux disease.

[0011] Furthermore, the non-erosive reflux disease is a spleen and stomach damp-heat type non-erosive reflux disease.

[0012] The present invention also provides a medicine for treating non-erosive reflux disease, wherein the medicine uses the above-mentioned traditional Chinese medicine composition as the active ingredient.

[0013] Furthermore, it also includes pharmaceutically acceptable excipients.

[0014] The present invention also provides a method for preparing the above-mentioned drug, comprising the following steps:

[0015] Weigh the above-mentioned Chinese herbal medicine composition, mix it with water, soak it, heat it to boiling, decoct it, filter it, collect the filtrate, concentrate it, and the medicine is obtained.

[0016] Furthermore, the mass-to-volume ratio of the traditional Chinese medicine composition to the water is 1 g: 4 mL.

[0017] Furthermore, the soaking time is 1 hour; the decocting time is 2 hours.

[0018] The present invention discloses the following technical effects:

[0019] 1. Significant clinical efficacy: Clinical studies have shown that the traditional Chinese medicine composition (Qingre Jiangni Fang) provided by this invention has a total effective rate of 96.67% and a cure rate of 86.67% in treating patients with spleen and stomach damp-heat type NERD, which is significantly better than the control group (total effective rate 86.67%, cure rate 23.33%). It can effectively improve patients' clinical symptoms and 24-hour dynamic pH value of the esophagus, and improve patients' quality of life and mental health (such as relieving depression and anxiety).

[0020] 2. Clear Mechanism of Action: This invention fills the research gap in the mechanism of action of traditional Chinese medicine in treating NERD, and reveals the modern pharmacological mechanism of "Qingre Jiangni Fang" in treating NERD. That is, by regulating the PKA / TRPV1 signaling pathway, it reduces the number of SP and CGRP positive nerve fibers that are closely related to visceral hypersensitivity and changes their expression intensity, thereby reducing esophageal visceral hypersensitivity. It elucidates the scientific connotation of its traditional Chinese medicine treatment method of "clearing heat and dampness, harmonizing the stomach and relieving nausea, and promoting qi circulation and bowel movement" at the molecular level.

[0021] 3. Outstanding comprehensive therapeutic effect: This formula not only effectively relieves clinical symptoms but also improves esophageal motility, resists esophageal reflux, and has an ideal acid-suppressing effect, achieving a comprehensive approach that addresses both the symptoms and the root cause, targeting multiple points. Furthermore, it has high safety, with few and mild adverse reactions during clinical application, mainly mild diarrhea, which can be relieved without special treatment. Its safety profile is superior to some Western medicines.

[0022] 4. High application value: This invention can be widely applied in clinical practice, overcoming the shortcomings of using proton pump inhibitors and other Western medicines alone to treat NERD, such as insufficient efficacy, high cost, and high relapse rate. It provides a new strategy for integrated traditional Chinese and Western medicine treatment. In the future, it can be developed into a standardized traditional Chinese medicine, possessing significant clinical promotion and economic value. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 The graph shows the statistical results of SP, CGRP positive fiber count, and mean optical density (OD) values ​​in the negative control group and the treatment group before drug administration.

[0025] Figure 2 The images show the optical microscopic results of SP positive fibers; where A represents the negative control group; B represents the treatment group before drug administration; and C represents the treatment group after drug administration.

[0026] Figure 3 The images show the optical microscopic results of CGRP-positive fibers; where A represents the negative control group; B represents the treatment group before drug administration; and C represents the treatment group after drug administration.

[0027] Figure 4 Electron microscopy results of the ultrastructural changes of synaptic vesicles in nerve fibers of mucosal cells in the lower esophagus; where A is the negative control group; B is the treatment group before drug administration; and C is the treatment group after drug administration. Detailed Implementation

[0028] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0029] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0030] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0031] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0032] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0033] Example 1

[0034] 1. Drug composition

[0035] A traditional Chinese medicine compound for treating non-erosive reflux disease, "Qingre Jiangni Fang", consists of 10g persimmon calyx, 5g clove, 15g immature bitter orange, 20g raw atractylodes macrocephala, 9g bupleurum, 10g codonopsis, 9g ginger pinellia, 9g scutellaria, 6g prepared licorice, 12g eupatorium, 30g stir-fried cassia seed and 20g calcined oyster shell.

[0036] In this invention, persimmon calyx and clove are used synergistically, forming a classic herbal pair for relieving nausea and vomiting, directly addressing the core symptoms of acid reflux and belching. Calcined oyster shell is salty and neutral, capable of softening and dispersing nodules to relieve esophageal mucosal stagnation, as well as neutralizing acid and relieving pain, reducing the irritation of gastric acid on the mucosa. Fructus Aurantii Immaturus breaks up qi stagnation, eliminates phlegm and removes lumps, while Radix Bupleuri soothes the liver, relieves depression, and regulates qi. The two herbs, one ascending and one descending, regulate the qi mechanism of the liver and stomach. Rhizoma Atractylodis Macrocephalae strengthens the spleen, replenishes qi, dries dampness, and promotes diuresis, while Radix Codonopsis pilosula tonifies the middle jiao and replenishes qi. The combination of these two herbs strengthens the spleen and eliminates dampness to eradicate the source of phlegm and dampness. Ginger-processed Pinellia ternata dries dampness, resolves phlegm, and relieves nausea and vomiting, thus enhancing the nausea-reducing effect of the principal herb. Scutellaria baicalensis, combined with Pinellia ternata, clears damp-heat in the stomach through its pungent and bitter properties. Eupatorium fortunei aromatically resolves dampness, invigorates the spleen and stomach, and improves abdominal distension caused by dampness obstructing the middle burner. Fried Cassia tora clears the liver, improves vision, and moistens the intestines to relieve constipation. It not only moderates the warming and drying properties of cloves and Pinellia ternata but also clears the bowels to reduce stomach qi, achieving the principle of "when the bowel qi is unobstructed, the stomach qi descends." Prepared licorice root tonifies the middle burner and replenishes qi, harmonizes the other herbs, moderates the strong effects of Citrus aurantium and Scutellaria baicalensis in the formula, and protects the qi of the spleen and stomach.

[0037] 2. Preparation method

[0038] Weigh each of the drugs in the "Heat-Clearing and Anti-emetic Formula" of this invention, add 620 mL of water, soak for 1 h, heat to boiling, maintain a gentle boil for 2 h, cool to room temperature, filter and collect the filtrate, and concentrate the filtrate to 310 mL.

[0039] Example 2: Clinical observation of the efficacy of Qingre Jiangni Decoction in treating NERD of spleen and stomach damp-heat type.

[0040] 1. Inclusion and exclusion criteria for patients with non-erosive gastroesophageal reflux disease (NERD) of the spleen and stomach damp-heat type

[0041] 1.1 Inclusion Criteria

[0042] Patients must meet all of the following criteria to be eligible for inclusion:

[0043] Western medicine diagnosis: Meets the diagnostic criteria for non-erosive gastroesophageal reflux disease (NERD).

[0044] Typical symptoms: Clear heartburn and / or reflux symptoms, with a course of illness ≥3 months.

[0045] Endoscopic diagnosis: Gastroscopy confirmed that there was no damage to the esophageal mucosa (Los Angeles grade A or normal), and no organic lesions such as Barrett's esophagus, esophageal ulcers, or strictures were found.

[0046] Traditional Chinese Medicine (TCM) diagnosis: It meets the TCM diagnostic criteria for damp-heat syndrome of the spleen and stomach.

[0047] Main symptoms: ① Heartburn, acid reflux; ② Abdominal fullness or bloating; ③ Sticky or bitter taste in the mouth.

[0048] Secondary symptoms: ① poor appetite and reduced food intake; ② heaviness in the body; ③ sticky or loose stools; ④ short and yellow urine.

[0049] Tongue and pulse: The tongue is red with a yellow and greasy coating; the pulse is slippery and rapid or soft and rapid.

[0050] Diagnostic requirements: at least 2 primary symptoms + 2 secondary symptoms, combined with typical tongue and pulse findings.

[0051] Symptoms and treatment history:

[0052] Within the past two weeks, the reflux disease questionnaire (RDQ) score or the gastroesophageal reflux disease questionnaire (GerdQ) score has reached a moderate or higher level.

[0053] Candidates must not have regularly taken proton pump inhibitors, H2 receptor antagonists, prokinetic drugs, or traditional Chinese medicine / decoctions with heat-clearing and dampness-resolving effects within one week prior to screening.

[0054] 1.2 Exclusion Criteria

[0055] Applicants meeting any of the following criteria will be excluded:

[0056] Disease-related exclusions:

[0057] Other esophageal diseases: erosive esophagitis (Los Angeles Class B or above) found on gastroscopy, Barrett's esophagus, hiatal hernia (diameter >3cm), esophageal cancer or suspected cancer, esophageal varices, confirmed eosinophilic esophagitis, etc.

[0058] Other upper gastrointestinal diseases: diagnosed peptic ulcer (active phase), gastroduodenal tumor, gastric cancer, and history of gastroesophageal surgery.

[0059] Overlapping symptoms: Diseases that may cause confusion with each other's symptoms, such as functional dyspepsia, irritable bowel syndrome, coronary heart disease, bronchial asthma, etc.

[0060] Serious systemic diseases: serious primary diseases of the heart, liver, kidneys, hematopoietic system, endocrine system, etc., or mental illnesses.

[0061] Other infections or inflammations: active hepatitis, tuberculosis, and other systemic infectious diseases.

[0062] Exclusion of specific groups and special circumstances:

[0063] Pregnant or breastfeeding women, or those planning to become pregnant within the next 6 months.

[0064] Individuals allergic to any known component of the drug used in the research.

[0065] History of alcohol or drug abuse.

[0066] Patients who have used medications that may affect gastrointestinal motility or gastric acid secretion for an extended period of the first 4 weeks (such as calcium channel blockers, anticholinergics, theophylline, bisphosphonates, nonsteroidal anti-inflammatory drugs, etc.) and are unable to discontinue use during the trial.

[0067] Those currently participating in other clinical trials.

[0068] 2. Administration method

[0069] Sixty patients with NERD of spleen and stomach damp-heat type were randomly divided into a treatment group and a control group, with 30 patients in each group. The treatment group was given the heat-clearing and rebellious-reducing formula of this invention, 200 mL of water decoction, one dose in the morning and one in the evening, taken warm half an hour after meals, combined with esomeprazole magnesium enteric-coated tablets 40 mg, once a day, taken orally in the morning; the control group was given conventional Western medicine esomeprazole magnesium enteric-coated tablets 40 mg, once a day, taken orally in the morning. The treatment course was 8 weeks.

[0070] 3. Observation Indicators

[0071] This includes pre- and post-treatment clinical symptom scores (RDQ score) and 24-hour esophageal pH monitoring values ​​(DeMeester score). The efficacy evaluation criteria were based on the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines".

[0072] 4. Results

[0073] 4.1 RDQ Integrals

[0074] As shown in Table 1, the scores of all symptoms in the treatment group decreased significantly after treatment compared with those before treatment (P<0.01), and the differences in RDQ scores of all symptoms between the groups after treatment were statistically significant (P<0.01).

[0075] Table 1 Comparison of RDQ scores before and after treatment in each group

[0076]

[0077] Note: ▲ This indicates that compared with the group before treatment, P<0.05; ※ This indicates that compared with the control group, P<0.05.

[0078] The results of the comparison of the total effective rate after RDQ treatment are shown in Table 2. The rank-sum test showed that the difference in efficacy between the treatment group and the control group was statistically significant (P<0.01), and the total effective rate of the treatment group was higher than that of the control group.

[0079] Table 2 Overall effective rate after RDQ treatment

[0080]

[0081] 4.2 DeMeester rating

[0082] The results of the DeMeester scores obtained from the 24-hour dynamic pH measurement of the esophagus before and after treatment in the two groups are shown in Table 3. The DeMeester scores of both groups decreased before and after treatment (P<0.05). After treatment, the acid suppression effect of the treatment group was better than that of the control group.

[0083] Table 3 Comparison of DeMeester scores before and after treatment in each group

[0084]

[0085] 4.3 Clinical efficacy

[0086] As shown in Table 4, the total effective rate in the treatment group was 96.67%, and the cure rate was 86.67%; the total effective rate in the control group was 86.67%, and the cure rate was 23.33%. The treatment group was significantly better than the control group in both aspects.

[0087] Table 4. Clinical syndrome cure rate

[0088]

[0089] In summary, both groups of patients showed significant improvement in RDQ scores, but the treatment group showed greater improvement than the control group. The total effective rate of TCM syndrome differentiation in the group using Qingre Jiangni Fang combined with esomeprazole sodium enteric-coated tablets was 96.67%, while the total effective rate in the esomeprazole sodium enteric-coated tablets group was 86.67%, indicating that Qingre Jiangni Fang combined with esomeprazole sodium enteric-coated tablets was superior to the control group in improving TCM syndrome differentiation in NERD patients. The treatment group was more effective in reducing DeMeester scores (acid suppression). No abnormalities were found in liver and kidney function tests before and after the trial, and no gastrointestinal allergic reactions occurred, indicating that Qingre Jiangni Fang is safe for clinical use.

[0090] Example 3: Effects of Qingre Jiangni Decoction on CGRP and SP in esophageal tissue of NERD patients with visceral hypersensitivity and damp-heat in the spleen and stomach.

[0091] 1. Test Methods

[0092] Sixty patients with typical gastroesophageal reflux disease (NERD) symptoms, diagnosed as spleen and stomach damp-heat type, were selected (inclusion and exclusion criteria were the same as in Example 2). A negative control group of 10 healthy individuals was also selected and did not receive medication. Based on the esophageal sensitivity to sac dilation stimulation and acid stimulation, and using the initial perception threshold of normal individuals ± 1.96 as the standard, visceral hypersensitivity modeling was performed on the 60 patients meeting the inclusion criteria. They were then randomly divided into two groups: an experimental group (n=30) and a model control group (n=30). The experimental group received a heat-clearing and reversing formula, taken twice daily, half an hour after meals. The model control group received a placebo of high-quality Chinese herbal granules, taken once daily, dissolved in 200 mL of water, half an hour after meals.

[0093] 2. Monitoring Indicators

[0094] The study compared the TCM syndrome scores before and after treatment in both groups, as well as the number of SP and CGRP positive fibers, the average optical density (OD) value, and the ultrastructural changes of synaptic vesicles in nerve fibers. The efficacy evaluation criteria were based on the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines" (Trial) and the "Consensus Opinions on the Diagnosis and Treatment of Gastroesophageal Reflux Disease with Traditional Chinese Medicine".

[0095] 3. Results

[0096] 3.1 Traditional Chinese Medicine Syndrome Scoring

[0097] As shown in Tables 5 and 6, after treatment, the total TCM syndrome score and the TCM single syndrome score of both groups of patients were significantly lower than before treatment. Moreover, the treatment group was significantly better than the model control group in terms of improving the total TCM syndrome score and the single syndrome score after treatment.

[0098] Table 5 Comparison of total TCM syndrome scores before and after treatment in each group ([M(P25,P75)])

[0099]

[0100] Table 6 Comparison of TCM symptom scores before and after treatment in each group ([M(P25,P75)])

[0101]

[0102] 3.2 SP positive fiber count, CGRP positive fiber count, and average optical density (OD) value

[0103] like Figures 1-3As shown, the number of SP and CGRP-positive nerve fibers in the treatment group before drug administration was significantly higher than that in the negative control group (P < 0.05), and the mean optical density (OD) value in the treatment group before drug administration was significantly higher than that in the negative control group (P < 0.05). This indicates that the number of SP and CGRP-positive nerve fibers in the lower esophageal cells of patients with visceral hypersensitivity NERD is significantly higher than that in normal individuals.

[0104] As shown in Table 7, the number of SP positive fibers in the treatment group was significantly lower than that before treatment after treatment (P<0.05), while the number of SP positive fibers in the model control group did not change significantly before and after treatment (P>0.05), and the number of SP positive fibers in the treatment group was significantly lower than that in the model control group after treatment (P<0.05).

[0105] Table 7 Comparison of SP-positive fiber counts before and after treatment in each group of patients

[0106]

[0107] Note: ▲ This indicates that compared with the group before treatment, P<0.05; ※ This indicates that compared with the model control group, P < 0.05.

[0108] As shown in Table 8, the number of CGRP-positive fibers in the treatment group was significantly lower than that before treatment after treatment (P<0.05), while the number of CGRP-positive fibers in the model control group did not change significantly before and after treatment (P>0.05), and the number of CGRP-positive fibers in the treatment group was significantly lower than that in the model control group after treatment (P<0.05).

[0109] Table 8 Comparison of the number of CGRP-positive fibers before and after treatment in each group of patients

[0110]

[0111] Note: ▲ This indicates that compared with the group before treatment, P<0.05; ※ This indicates that compared with the model control group, P < 0.05.

[0112] As shown in Table 9, the average optical density value of the patients in the treatment group was significantly lower than that before treatment after treatment (P<0.05), while the average optical density value of the model control group did not change significantly before and after treatment (P>0.05), and the average optical density value of the treatment group was significantly lower than that of the model control group after treatment (P<0.05).

[0113] Table 9 Comparison of mean optical density (OD) values ​​before and after treatment in each group of patients

[0114]

[0115] Note: ▲ This indicates that compared with the group before treatment, P<0.05; ※ This indicates that compared with the model control group, P < 0.05.

[0116] After treatment, the number of SP and CGRP-positive fibers and the average optical density (OD) value in the treatment group were significantly lower than before treatment. Furthermore, the number of SP and CGRP-positive fibers and the average optical density (OD) value in the treatment group were significantly lower than those in the model control group after treatment. This indicates that the heat-clearing and counterflow-relieving formula of this invention can exert a therapeutic effect by reducing the number of SP and CGRP-positive fibers in the esophageal tissue of patients with visceral hypersensitivity NERD.

[0117] 3.3 Ultrastructural changes of synaptic vesicles in nerve fibers of mucosal cells in the lower esophagus

[0118] like Figure 4 As shown, transmission electron microscopy revealed that the terminal synaptic vesicles of esophageal mucosal cells in the blank control group were predominantly agranular vesicles. In the treatment group before medication, esophageal cells contained numerous synaptic vesicle-containing swellings and nerve terminals, with the synaptic vesicles being predominantly large granular vesicles. Compared to the treatment group before medication, the large granular vesicles within the nerve swellings of esophageal wall cells in the treatment group after 8 weeks of medication were significantly sparser. This clearly demonstrates the effect of the heat-clearing and reversing formula of this invention on improving the morphology and quantity of synaptic vesicles in esophageal nerve fibers, supporting its repair effect on the microstructure of esophageal nerve fibers.

[0119] In summary, after treatment, the total TCM syndrome score, TCM single syndrome score, number of SP and CGRP positive fibers, and mean optical density (OD) value of both groups of patients were significantly lower than before treatment. Moreover, after medication, the large granular vesicles in the esophageal parietal cell nerve swellings in the treatment group were significantly less numerous than before treatment and in the model control group. This indicates that the Qingre Jiangni formula can change the ultrastructure of synaptic vesicles in esophageal nerve fibers in patients with visceral hypersensitivity NERD, and at the same time, it can reduce the number of SP and CGRP positive nerve fibers closely related to visceral hypersensitivity and change their mean optical density (OD) value, thus playing a therapeutic role.

[0120] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A traditional Chinese medicine composition, characterized in that, It includes the following components: persimmon calyx, clove, immature bitter orange, raw atractylodes macrocephala, bupleurum, codonopsis, ginger-processed pinellia, scutellaria baicalensis, prepared licorice root, eupatorium fortunei, stir-fried cassia seed, and calcined oyster shell.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, By weight, it includes the following components: 10 parts persimmon calyx, 5 parts clove, 15 parts immature bitter orange, 20 parts raw atractylodes macrocephala, 9 parts bupleurum, 10 parts codonopsis, 9 parts ginger-processed pinellia, 9 parts scutellaria baicalensis, 6 parts prepared licorice, 12 parts eupatorium fortunei, 30 parts stir-fried cassia seed and 20 parts calcined oyster shell.

3. The use of the traditional Chinese medicine composition according to claim 1 or 2 in the preparation of a medicament for treating gastroesophageal reflux disease.

4. The application as described in claim 3, characterized in that, The gastroesophageal reflux disease mentioned is non-erosive reflux disease.

5. The application as described in claim 4, characterized in that, The non-erosive reflux disease is classified as spleen and stomach damp-heat type non-erosive reflux disease.

6. A drug for treating non-erosive reflux disease, characterized in that, The drug uses the traditional Chinese medicine composition as described in claim 1 or 2 as its active ingredient.

7. The drug as described in claim 6, characterized in that, It also includes pharmaceutically acceptable excipients.

8. A method for preparing the drug according to claim 6, characterized in that, Includes the following steps: Weigh out the traditional Chinese medicine composition according to claim 1 or 2, mix it with water, soak it, heat it to boiling, decoct it, filter it, collect the filtrate, concentrate it, and the medicine is obtained.

9. The preparation method according to claim 8, characterized in that, The mass-to-volume ratio of the traditional Chinese medicine composition to the water is 1 g: 4 mL.

10. The preparation method according to claim 8, characterized in that, The soaking time is 1 hour; the decocting time is 2 hours.

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