Application of a Chinese medicine composition in preparing a medicine for treating liver-stomach stagnation heat type reflux esophagitis

Abstract

The invention discloses a kind of application of Chinese medicine composition in the preparation of treatment liver and stomach stagnation heat type reflux esophagitis medicine, belongs to the field of medical technology, by weight, the above-mentioned Chinese medicine composition includes the following components: 150-350 parts of gallnut, 800-1200 parts of Sophora japonica, 800-1200 parts of white mulberry, 800-1200 parts of Selaginella, 800-1200 parts of Sanguisorba officinalis, 15-35 parts of cholic acid, and the whole prescription is reasonable. Animal experiment research finds that the Chinese medicine composition can significantly repair esophageal tissue mucosal damage, inhibit mucosal inflammatory reaction, and has significant anti-reflux esophagitis effect. Further clinical studies show that the Chinese medicine composition of the present invention can improve the clinical symptoms of patients with liver and stomach stagnation heat type reflux esophagitis, and the total clinical effective rate reaches 96.0%, with broad application prospects.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and particularly relates to an application of a traditional Chinese medicine composition in preparing a medicine for treating liver-stomach stagnation heat type reflux esophagitis. Background Art

[0002] Reflux esophagitis refers to an inflammatory reaction of the esophagus caused by the reflux of gastric contents and gastric acid into the esophagus. The patients often present with acid reflux, heartburn and chest pain. In severe cases, complications such as esophageal bleeding and ulcers may occur, posing a threat to the patient's health. According to its clinical manifestations, Chinese medicine classifies it into categories such as acid vomiting, acid swallowing, noisy stomach, vomiting, chest fullness, and esophageal congestion. The "Expert Consensus on Diagnosis and Treatment of Gastroesophageal Reflux Disease in Traditional Chinese Medicine (2017)" issued by the Digestive Diseases Committee of the Chinese Association of Integrated Traditional Chinese and Western Medicine divides reflux esophagitis into the following six syndromes: liver and stomach heat syndrome, gallbladder heat attacking the stomach syndrome, qi stagnation and phlegm obstruction syndrome, blood stasis obstruction syndrome, middle deficiency qi reversal syndrome, and spleen deficiency damp-heat syndrome.

[0003] Epidemiological surveys show that the incidence of reflux esophagitis is highest in the United States, with about 20% of adults suffering from reflux esophagitis. The incidence in Europe is about 10%, and the incidence in China is about 5-10%. With the change in dietary structure and the accelerated pace of life, the prevalence of reflux esophagitis in China is also increasing year by year. The symptoms of reflux esophagitis due to liver and stomach heat, such as acid reflux, heartburn, bitter taste in the mouth, and burning behind the sternum, will have an impact on the patient's life and psychology. In severe cases, it increases the risk of transformation to Barrett's esophagus and esophageal adenocarcinoma, and will also have a great impact on the patient's mental state and economic situation.

[0004] At present, the treatment methods for reflux esophagitis include drug therapy (PPI, potassium ion competitive inhibitors), endoscopic surgery (peroral incisionless fundoplication, radiofrequency ablation under the inner diameter), and traditional Chinese medicine treatment. Studies have shown that long-term use of PPIs can lead to side effects such as diarrhea, abdominal distension, malignancy, infection, etc., which will cause more gastrointestinal damage to patients, and up to 30% of patients have poor efficacy. These patients with refractory reflux esophagitis have a protracted and repeated course of disease, which not only affects the quality of life, but also requires repeated visits to the doctor, consuming a lot of medical resources. Traditional Chinese medicine treatment is based on the "holistic concept" and "differentiation and treatment", and has certain advantages in the treatment of reflux esophagitis. Through syndrome differentiation and treatment, traditional Chinese medicine not only has significant efficacy and low adverse reactions, but also can significantly reduce its recurrence rate. Summary of the invention

[0005] In view of the deficiencies in the prior art, the purpose of the present invention is to propose an application of a Chinese medicine composition in the preparation of a drug for treating liver-stomach heat type reflux esophagitis, which can fundamentally improve the clinical symptoms of patients with liver-stomach heat type reflux esophagitis, with an effective rate of up to 96.0%.

[0006] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] The invention provides an application of a traditional Chinese medicine composition in preparing a medicine for treating liver-stomach stagnation heat type reflux esophagitis. The traditional Chinese medicine composition comprises the following components in parts by weight: 150-350 parts of gallnut, 800-1200 parts of sophora japonica, 800-1200 parts of white ampelopsis, 800-1200 parts of selaginella, 800-1200 parts of sanguisorba officinalis and 15-35 parts of cholic acid.

[0008] In the Chinese medicine composition for preparing a medicine for treating reflux esophagitis of liver-stomach stagnation heat type, the Chinese gallnut reduces fire, astringes the intestines and absorbs dampness; the flower of Sophora japonica clears the liver, purges fire, cools blood and stops bleeding, and the two are used as the main drug. The white mulberry clears heat and detoxifies, and is the assistant drug. The selaginella and sanguisorba officinalis are used as auxiliary drugs to cool blood, stop bleeding and detoxify. Bile acid harmonizes the drugs. The whole prescription has reasonable compatibility, plays the role of clearing heat and harmonizing the stomach, soothing the liver and relieving depression, and has a significant clinical effect on reflux esophagitis of liver-stomach stagnation heat type.

[0009] Preferably, the Chinese medicine composition comprises the following components in parts by weight: 200-300 parts of Galla chinensis, 900-1100 parts of Sophora japonica, 900-1100 parts of Bletilla striata, 900-1100 parts of Selaginella truncatula, 900-1100 parts of Sanguisorba officinalis, and 20-30 parts of cholic acid.

[0010] More preferably, the Chinese medicine composition comprises the following components in parts by weight: 250 parts of Galla chinensis, 1000 parts of Sophora japonica, 1000 parts of Bletilla striata, 1000 parts of Selaginella truncatula, 1000 parts of Sanguisorba officinalis, and 25 parts of cholic acid.

[0011] Preferably, the drug for treating liver-stomach heat stagnation type reflux esophagitis is a drug that improves mucosal damage and inflammatory response in the esophageal tissue area.

[0012] Preferably, the reflux esophagitis drug further comprises a medically acceptable excipient.

[0013] More preferably, the medically acceptable excipients include fillers, surfactants, binders, antioxidants, preservatives, flavoring agents, lubricants, coating agents or coloring agents.

[0014] Preferably, the reflux esophagitis drug is an oral preparation or an injectable preparation.

[0015] More preferably, the oral preparation is a tablet, capsule, granule, powder, mixture, emulsion, decoction or suspension.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] Experiments have confirmed that the medicine for treating reflux esophagitis of liver and stomach stagnation heat type prepared by the Chinese medicine composition provided by the present invention can significantly repair esophageal tissue mucosal damage, inhibit mucosal inflammatory response, have anti-reflux esophagitis effects, and can fundamentally improve the clinical symptoms of patients with reflux esophagitis of liver and stomach stagnation heat type, with an effective rate of 96.0%. The whole prescription is reasonably compatible, and it can play the role of clearing heat and harmonizing the stomach, soothing the liver and relieving depression, and has a significant clinical effect on reflux esophagitis of liver and stomach stagnation heat type. DETAILED DESCRIPTION

[0018] The present invention is further described in detail below. The embodiments described are exemplary and intended to explain the present invention, but should not be construed as limiting the present invention.

[0019] Example 1 Evaluation of the pharmacological effects of Chinese medicine compositions with different proportions on rats with reflux esophagitis

[0020] 1. Research Methods

[0021] 1. Preparation of Chinese medicine compositions with different proportions

[0022] Recipe 1: Take 250 parts of Galla chinensis, 1000 parts of Sophora japonica, 1000 parts of Bletilla striata, 1000 parts of Selaginella truncatula, 1000 parts of Sanguisorba officinalis, and 25 parts of cholic acid. Soak the herbs in water for 30 minutes, then boil them three times, adding 7 times, 5 times, and 5 times the amount of water respectively, boiling for 30 minutes each time, and combine the three medicinal solutions for later use.

[0023] Recipe 2: Take 150 parts of Galla chinensis, 800 parts of Sophora japonica, 800 parts of Bletilla striata, 800 parts of Selaginella truncatula, 800 parts of Sanguisorba officinalis, and 15 parts of cholic acid. Soak the herbs in water for 30 minutes, then boil them three times, adding 7 times, 5 times, and 5 times the amount of water respectively, boiling for 30 minutes each time, and combine the three medicinal solutions for later use.

[0024] Recipe 3: Take 350 parts of Galla chinensis, 1200 parts of Sophora japonica, 1200 parts of Bletilla striata, 1200 parts of Selaginella truncatula, 1200 parts of Sanguisorba officinalis, and 35 parts of cholic acid. Soak the herbs in water for 30 minutes, then boil them three times, adding 7 times, 5 times, and 5 times the amount of water respectively, boiling for 30 minutes each time, and combine the three medicinal solutions for later use.

[0025] 2. Experimental animals and groups

[0026] A total of 120 SD male rats (SPF grade, weight (250±20) g) were randomly divided into a normal group, a model group, low-dose, medium-dose, and high-dose groups of Recipe 1, Recipe 2, and Recipe 3, and a positive drug group, with 10 rats in each group.

[0027] 3. Construction of Reflux Esophagitis Rat Model and Drug Administration

[0028] The rats were anesthetized with isoflurane inhalation. The normal group underwent abdominal incision, while the other groups underwent modified partial cardia myotomy + externalized partial pyloric ligation to establish the reflux esophagitis rat model.

[0029] After 7 days of modeling, restraint stress was continuously applied for 14 days. At the same time, the rats in the low, medium and high dose groups of Prescription 1, Prescription 2 and Prescription 3 were given corresponding doses by gavage, the rats in the positive drug group were given omeprazole by gavage, and the control group and the model group were given an equal volume of normal saline by gavage, 2 times / day, for 14 consecutive days. The dosage of the low, medium and high dose groups of Prescription 1, Prescription 2, Prescription 3 and the positive drug group is shown in Table 1. After 2 weeks of gavage, the rats were killed and the esophageal tissue was removed.

[0030] Table 1 Dosage of each group of animals

[0031]

[0032] 4. Determination of reflux esophagitis related indicators

[0033] (1) Pathological changes and scoring of esophageal mucosal tissue

[0034] The lower end of rat esophagus tissue was embedded in paraffin and sectioned, and the pathological changes of esophageal tissue were observed by hematoxylin-eosin staining, and pathological grading scores were performed. The grading standards refer to Table 2 "Guidelines for the diagnosis and treatment of reflux esophagitis (2003)".

[0035] Table 2 Pathological grading of reflux esophagitis

[0036]

[0037] (2) Determination of inflammatory factor levels

[0038] After 2 weeks of drug intervention, the serum of rats in each group was collected and centrifuged, and the levels of IL-1β, TNF-α, and IL-8 in the serum of each group were detected according to the instructions of the enzyme-linked immunosorbent assay (ELISA) kit.

[0039] (3) Statistical methods

[0040] Statistical analysis was performed using Prism 10 software, and the results were analyzed by t-test for inter-group testing. Data are expressed as mean ± standard deviation. P A value of <0.05 was considered significant.

[0041] (II) Experimental results

[0042] 1. Pathological changes of esophageal tissues in rats of each group

[0043] The esophageal mucosa of rats in the normal group was intact, and inflammatory cells and vacuoles were occasionally seen in the epithelial cell layer. The esophageal tissue of the model group showed inflammatory changes, with varying degrees of hyperplasia of the squamous epithelium and basal layer, disordered cell arrangement, extension of papillae in the mucosal lamina propria, and infiltration of varying numbers of inflammatory cells, scattered inflammatory cells; after drug intervention, the pathological manifestations of the esophageal tissue of rats in the low, medium, and high dose groups of Prescription 1, Prescription 2, Prescription 3, and the positive drug group were significantly improved, with mild hyperplasia of the squamous epithelium and a small number of inflammatory cells in the mucosal lamina propria. The pathological changes of the esophageal tissue of rats in each group after 14 days of drug intervention are shown in Table 3 below. It can be seen from the results in the table that the pathological grading of the esophageal tissue of rats in the low, medium, and high dose groups of Prescription 1, Prescription 2, and Prescription 3 was better than that of the positive drug group and the model group.

[0044] Table 3 Pathological changes in esophageal tissues of rats in each group after 14 days of drug intervention (%)

[0045]

[0046] 2. Levels of inflammatory factors

[0047] As shown in Table 4 below, compared with the control group, the levels of serum inflammatory factors IL-1β, TNF-α, and IL-8 in the model group were significantly increased ( P <0.05); compared with the model group, the serum IL-1β, TNF-α, and IL-8 levels of rats in the medium- and high-dose groups of Prescription 1, Prescription 2, and Prescription 3 and the positive drug group were significantly reduced ( P <0.05, and the Chinese medicine composition inhibited the level of inflammatory factors in a concentration-dependent manner. The difference was statistically significant ( P <0.05).

[0048] Table 4 Serum inflammatory factor levels in rats in each group (μg / L)

[0049]

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

[0051] 3. Conclusion

[0052] Chinese medicine compositions with different proportions can significantly improve the mucosal damage and inflammatory response in the esophageal tissue of rats with reflux esophagitis model, and have anti-reflux esophagitis effects.

[0053] Example 2 Evaluation of the clinical efficacy of a Chinese medicine composition on reflux esophagitis of the liver and stomach heat type

[0054] 1. Research Methods

[0055] 1. Experimental Grouping

[0056] One hundred male and female patients with liver-stomach stagnation heat type reflux esophagitis were selected and divided into a control group and an experimental group.

[0057] 2. Treatment methods

[0058] The decoction was prepared according to the drug ratio and preparation method of Part 1 in Example 1. The decoction was given to the patients in the experimental group three times a day, 150 ml each time.

[0059] The control group was given omeprazole enteric-coated capsules orally, 20 mg each time, twice a day.

[0060] One course of treatment was 4 weeks, and both groups received treatment for 4 weeks.

[0061] 3. Diagnostic criteria

[0062] Western medicine diagnostic criteria: Patients with reflux esophagitis are diagnosed through endoscopic examination. The diagnostic criteria refer to the "Consensus on the Diagnosis and Treatment of Gastroesophageal Reflux Disease with Integrated Traditional Chinese and Western Medicine (2017)" issued by the Digestive System Disease Professional Committee of the Chinese Association of Integrated Traditional Chinese and Western Medicine.

[0063] TCM diagnostic criteria: Refer to the TCM syndrome differentiation of liver and stomach heat stagnation in the "Expert Consensus on TCM Diagnosis and Treatment of Gastroesophageal Reflux Disease (2017)" issued by the Digestive Diseases Committee of the Chinese Association of Integrated Traditional Chinese and Western Medicine. Main symptoms: ① acid reflux; ② burning pain behind the sternum; ③ noisy. Secondary symptoms: ① irritability; ② fullness in the ribs; ③ dry mouth and bitter taste; ④ constipation. Tongue and pulse: red tongue, yellow tongue coating, and stringy and slippery pulse. Syndrome determination: If the patient has 2 main symptoms and 1 or 2 secondary symptoms, the diagnosis can be confirmed by referring to the tongue and pulse.

[0064] 4. Efficacy evaluation criteria

[0065] (1) Symptom severity classification and scoring criteria

[0066] Level 0 (0 points): no discomfort; Level I (1 point): symptoms are not obvious and are discovered under the doctor's suggestion; Level II (2 points): symptoms are between Level I and Level III; Level III (3 points): symptoms are obvious, affecting daily life, and occasional medication is required; Level IV (4 points): symptoms are between Level III and Level V; Level V (5 points): symptoms are very obvious, affecting daily life, and long-term medication is required.

[0067] (2) Scoring criteria for symptom frequency

[0068] Asymptomatic: 0 point; symptoms <1 day per week, 1 day, 2-3 days, 4-5 days, and almost every day are scored as 1-5 points respectively.

[0069] (3) Score for each symptom

[0070] Each symptom was scored plus the frequency of each symptom, with the maximum score for each symptom being 10 points; the total symptom score for each patient was the sum of the scores for each symptom.

[0071] (4) Symptom efficacy evaluation criteria

[0072] Markedly effective: clinical symptom score decreased by >80%; effective: clinical symptom score decreased; ineffective: clinical symptom score did not change.

[0073] 5. Statistical methods

[0074] Prism 10 software was used for statistical analysis. Symptom score results were analyzed by t-test for inter-group test. Data were expressed as mean ± standard deviation. P <0.05 was considered significant. 2 test.

[0075] (II) Test results

[0076] The clinical efficacy of the Chinese medicine composition in treating reflux esophagitis of liver and stomach stagnation type is shown in Tables 5 and 6. As can be seen from Table 5, after 4 weeks of treatment with the Chinese medicine composition tablets, the symptom score of the experimental group was significantly lower than that of the control group, and the difference was statistically significant ( P <0.05).

[0077] As can be seen from Table 6, the Chinese medicine composition can significantly improve the clinical symptoms of patients with liver and stomach stagnation type reflux esophagitis, with a total clinical effective rate of 96.0%, and the total effective rate is significantly higher than that of the Western medicine control group. All patients participating in the study had no adverse reactions and toxic side effects.

[0078] Table 5 Symptom scores before and after treatment

[0079]

[0080] Note: Compared with before treatment, * P <0.05, ** P <0.01; compared with the control group, # P <0.05, ## P <0.01

[0081] Table 6 Clinical efficacy after treatment

[0082]

[0083] Note: Compared with the control group, * P <0.05, **P <0.01

[0084] 3. Conclusion

[0085] It can be seen from the above experiments that the Chinese medicine composition has a reasonable formulation, can significantly repair esophageal tissue mucosal damage and inhibit mucosal inflammatory response. Clinical studies have confirmed that it can fundamentally improve the clinical symptoms of patients with liver and stomach heat type reflux esophagitis, with an effective rate of 96.0%.

[0086] In actual clinical applications, the Chinese medicine composition can be provided to patients in the form of tablets, capsules, granules, powders, mixtures, emulsions, decoctions or suspensions according to actual needs. The amount can also be increased or decreased according to the basic dosage based on the patient's constitution. For example, a Chinese medicine composition is provided, comprising the following components in parts by weight: 250 parts of Galla chinensis, 1000 parts of Sophora japonica, 1000 parts of Bletilla striata, 1000 parts of Selaginella thunbergii, 1000 parts of Sanguisorba officinalis, and 25 parts of cholic acid, and the mixture is prepared according to the existing method.

[0087] Alternatively, a Chinese medicine composition is provided, comprising the following components, by weight: 250 parts of Galla chinensis, 1000 parts of Sophora japonica, 1000 parts of Bletilla striata, 1000 parts of Selaginella truncatula, 1000 parts of Sanguisorba officinalis, and 25 parts of cholic acid, and the composition is made into capsules according to the existing method.

[0088] Alternatively, a Chinese medicine composition is provided, comprising the following components, by weight: 250 parts of Galla chinensis, 1000 parts of Sophora japonica, 1000 parts of Bletilla striata, 1000 parts of Selaginella truncatula, 1000 parts of Sanguisorba officinalis, and 25 parts of cholic acid, and the composition is made into a powder according to an existing method.

[0089] Alternatively, a Chinese medicine composition is provided, comprising the following components, by weight: 250 parts of Galla chinensis, 1000 parts of Sophora japonica, 1000 parts of Bletilla striata, 1000 parts of Selaginella truncatula, 1000 parts of Sanguisorba officinalis, and 25 parts of cholic acid, and the composition is prepared into a suspension according to an existing method.

[0090] Alternatively, a Chinese medicine composition is provided, comprising the following components, by weight: 250 parts of Galla chinensis, 1000 parts of Sophora japonica, 1000 parts of Bletilla striata, 1000 parts of Selaginella truncatula, 1000 parts of Sanguisorba officinalis, and 25 parts of cholic acid, and the composition is made into granules according to an existing method.

[0091] The above are only some embodiments of the present invention. For those skilled in the art, several modifications and improvements can be made without departing from the creative concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. Use of a Chinese medicine composition in the preparation of a drug for treating reflux esophagitis of liver and stomach stagnation type, characterized in that: The traditional Chinese medicine composition consists of 150-350 parts of gallnut, 800-1200 parts of Sophora japonica, 800-1200 parts of Bletilla striata, 800-1200 parts of Selaginella, 800-1200 parts of Sanguisorba officinalis and 15-35 parts of cholic acid in parts by weight.

2. The use of the Chinese medicine composition according to claim 1 in the preparation of a drug for treating reflux esophagitis of liver and stomach stagnation type, characterized in that: The traditional Chinese medicine composition consists of 200-300 parts of gallnut, 900-1100 parts of Sophora japonica, 900-1100 parts of Bletilla striata, 900-1100 parts of Selaginella truncatula, 900-1100 parts of Sanguisorba officinalis and 20-30 parts of cholic acid in parts by weight.

3. The use of the Chinese medicine composition according to claim 2 in the preparation of a drug for treating reflux esophagitis of liver and stomach stagnation type, characterized in that: In parts by weight, the traditional Chinese medicine composition consists of 250 parts of gallnut, 1000 parts of Sophora japonica, 1000 parts of Bletilla striata, 1000 parts of Selaginella truncatula, 1000 parts of Sanguisorba officinalis, and 25 parts of cholic acid.

4. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a drug for treating reflux esophagitis of liver and stomach heat stagnation type, characterized in that: The drug for treating liver-stomach heat stagnation type reflux esophagitis is a drug for improving mucosal damage and inflammatory response in esophageal tissue.

5. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a drug for treating reflux esophagitis of liver and stomach heat stagnation type, characterized in that: The reflux esophagitis drug further comprises medically acceptable adjuvants.

6. Use of the Chinese medicine composition according to claim 5 in preparing a drug for treating reflux esophagitis of liver and stomach stagnation heat type, characterized in that: The medically acceptable excipients include fillers, surfactants, binders, antioxidants, preservatives, flavoring agents, lubricants, coating agents or coloring agents.

7. Use of the Chinese medicine composition according to claim 1 in preparing a drug for treating reflux esophagitis of liver and stomach stagnation heat type, characterized in that: The reflux esophagitis medicine is an oral preparation or an injection preparation.

8. Use of the Chinese medicine composition according to claim 7 in preparing a drug for treating reflux esophagitis of liver and stomach stagnation heat type, characterized in that: The oral preparation is a tablet, capsule, granule, powder, mixture, emulsion, decoction or suspension.

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