Traditional Chinese medicine compound for treating liver-stomach stagnated heat syndrome of gastroesophageal reflux disease as well as preparation method and application of traditional Chinese medicine compound

Abstract

The invention discloses a traditional Chinese medicine compound for treating liver-stomach stagnated heat syndrome of gastroesophageal reflux disease as well as a preparation method and application of the traditional Chinese medicine compound. The traditional Chinese medicine compound is prepared from the following raw materials in parts by weight: 8 to 12 parts of herba inulae, 10 to 30 parts of ruddle, 2 to 10 parts of rhizoma coptidis, 3 to 10 parts of radix scutellariae, 3 to 10 parts of rhizoma zingiberis, 10 to 15 parts of spica prunellae, 3 to 10 parts of fructus citri sarcodactylis, 10 to 30 parts of cuttlebone, 5 to 10 parts of rhizoma pinelliae, 10 to 30 parts of radix pseudostellariae, 10 to 15 parts of radix glehniae and 2 to 10 parts of liquorice root.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine compound for treating gastroesophageal reflux disease liver-stomach stagnation heat syndrome and its preparation method and application Background Art

[0002] Gastroesophageal Reflux Disease (GERD) is one of the common diseases in gastroenterology. Its clinical symptoms include esophageal manifestations such as acid reflux, heartburn, and pain behind the sternum, and extraesophageal manifestations such as choking, throat discomfort, dental erosion, and asthma. It has attracted much attention due to its diverse clinical symptoms, poor effect of Western medicine treatment, and easy recurrence after drug withdrawal. At present, Western medicine treatment methods mainly inhibit gastric acid secretion, and proton pump inhibitors (PPI) or potassium-competitive acid blockers (P-CABs) are the first choice. Studies have found that nearly 1 / 3 of patients cannot alleviate reflux symptoms after double-dose acid suppression therapy (see reference 1), which is called refractory gastroesophageal reflux disease. The reason may be that acid suppression therapy cannot effectively solve the relaxation of the patient's lower esophageal sphincter and cannot solve non-acid reflux. In recent years, the safety of long-term use of such drugs has been questioned. Many studies have reported that long-term use of such drugs is associated with an increased risk of acute and chronic kidney disease, rhabdomyolysis, and kidney stones (see References 2, 3, and 4), which has limited their application. Therefore, seeking a more effective treatment method to improve the clinical symptoms of GERD patients, reduce the recurrence of clinical symptoms, and have fewer adverse reactions is an urgent problem to be solved in clinical practice.

[0003] In recent years, traditional Chinese medicine has achieved good clinical efficacy in the treatment of GERD. Modern doctors mostly classify it as "esophageal reflux" and "acid vomiting". The advantage of traditional Chinese medicine treatment is to treat patients according to syndrome differentiation and give patients individualized treatment. The effect of traditional Chinese medicine treatment depends on the accuracy of syndrome differentiation. The 2023 consensus opinion of experts on the diagnosis and treatment of gastroesophageal reflux disease in traditional Chinese medicine (see reference 5) divides this disease into 7 syndromes: liver-stomach stagnation and heat syndrome, gallbladder fire upward syndrome, qi stagnation and phlegm obstruction syndrome, chest yang deficiency syndrome, middle deficiency and qi reversal syndrome, spleen deficiency and damp-heat syndrome, and stomach yin deficiency syndrome. Among them, liver-stomach stagnation and heat syndrome must meet the following 2 main symptoms (heartburn, acid reflux), 2 secondary symptoms (burning pain behind the sternum, burning pain in the stomach, hunger, irritability, belching or regurgitation, abdominal distension), tongue (red tongue, yellow tongue coating), and pulse (stringy pulse) before diagnosis.

[0004] Reference List:

[0005] Document 1: EI-Serag H, Becher A, Jones R. Systematic review: persistent refluxsymptoms on proton pump inhibitor therapy in primary care and communities studies [J]. Aliment Pharmacol Ther, 2010, 32: 720-737.

[0006] Document 2: Emily Hart, Terry Dunn, Steven Feuerstein, et al. Proton PumpInhibitors and Risk of Acute and Chronic Kidney Disease: A RetrospectiveCohort Study[J].Pharmacotherapy.2019,39(4):443-453.

[0007] Document 3: Scott J Duncan, Colin W Howden. Proton Pump Inhibitors and Risk of Rhabdomyolysis[J]. Drug Saf, 2017, 40(1):61-64.

[0008] Document 4: Wilson Sui, Nicole Miller, Edward R Gould, et al. Proton pumpinhibitors use and risk of incident nephrolithiasis[J]. Urolithiasis, 2022, 50(4): 401-409.

[0009] Reference 5: Chinese Association of Traditional Chinese Medicine Spleen and Stomach Disease Branch. Expert consensus on TCM diagnosis and treatment of gastroesophageal reflux disease (2023). Journal of Traditional Chinese Medicine [J], 2023, 64(18): 1935-1944. Summary of the invention

[0010] In view of the shortcomings of the prior art described above, the purpose of the present invention is to provide an oral Chinese medicine compound for treating gastroesophageal reflux disease with liver and stomach heat syndrome, so as to solve the problem in the prior art of lack of an oral Chinese medicine compound with effective therapeutic effect for improving clinical symptoms and reducing the recurrence of clinical symptoms.

[0011] In order to achieve the above-mentioned object and other related objects, the present invention provides the following technical solutions:

[0012] The first aspect of the present invention provides a Chinese medicinal compound for treating gastroesophageal reflux disease with liver-stomach stagnation and heat syndrome, comprising the following raw materials in weight ratio:

[0013] Inula Britannica L.var chinensis (Rupr.) Reg, 8-12 copies

[0014] Ochre, Haematitum, 10-30 parts

[0015] Coptis chinensis Franch, 2-10 parts

[0016] Scutellaria baicalensis Georgi, 3-10 parts

[0017] Dried ginger, Zingiber officinale Rosc, 3-10 parts

[0018] Prunella vulgaris L, 10-15 parts

[0019] Buddha's hand, Citrus medica L.var.sarcodactylis Swingle, 3-10 servings

[0020] Cuttlebone, Sepiella maindroni de Rochebrune, 10-30 portions

[0021] Pinellia ternate (Thunb.) Breit., 5-10 portions

[0022] Pseudostellaria heterophylla (Miq.) Pax ex Pax et Hoffm., 10-30 parts

[0023] Glehnia littoralis F.Schmidt ex Miq., 10-15g serving

[0024] Licorice, Glycyrrhiza uralensis Fisch., 2-10 parts.

[0025] Among them, Jinfeicao is the above-ground part of the perennial herbaceous plant Inula rutaecarpa of the Asteraceae family, which is salty, slightly bitter, warm, and enters the lung, spleen, stomach, and large intestine meridians, and has the effects of descending qi, resolving phlegm and relieving cough. Daizheshi is an ore of hematite of the oxide mineral corundum family, which is bitter and cold in nature and enters the liver and pericardium meridians, and has the effects of descending qi, stopping vomiting and relieving asthma, cooling blood and stopping bleeding, and calming liver yang. Coptis chinensis is the rhizome, root hair and leaf of the perennial herb Coptis chinensis of the Ranunculaceae family, which is bitter and cold in nature and enters the heart, liver, stomach, and large intestine meridians, and has the effects of clearing heat and drying dampness, purging fire and detoxifying. Scutellaria baicalensis is the root of the perennial herb Scutellaria baicalensis of the Lamiaceae family, which is bitter and cold in nature and enters the lung, gallbladder, stomach, and large intestine meridians, and has the effects of clearing heat and drying dampness, purging fire and detoxifying, stopping bleeding, and calming the fetus. Dried ginger is the dried rhizome of ginger, a perennial herb of the ginger family. It is pungent and hot in nature and enters the spleen, stomach, heart and lung meridians. It has the functions of warming the middle, restoring yang, warming the lungs and eliminating phlegm. Prunella vulgaris is the fruit spike with flowers of the perennial plant Prunella vulgaris of the Lamiaceae family. It is bitter, pungent and cold in nature and enters the liver and gallbladder meridians. It has the functions of clearing liver fire and dispersing depression. Citron is the fruit of Citron, an evergreen small tree or shrub of the Rutaceae family. It is pungent, bitter and warm in nature and enters the liver, spleen, stomach and lung meridians. It has the functions of soothing the liver and regulating qi, harmonizing the middle and eliminating phlegm. Cuttlebone is the inner shell of the needleless mullet of the mullet family. It is salty, astringent and slightly warm in nature and enters the liver and kidney meridians. It has the functions of relieving acid and relieving pain, astringing and stopping bleeding, consolidating essence and stopping leukorrhea, and collecting moisture and healing sores. Pinellia ternata is the tuber of the perennial herbaceous plant Pinellia ternata of the Araceae family. It is pungent and warm in nature and enters the spleen, stomach and lung meridians. It has the effects of drying dampness and resolving phlegm, relieving adverse reactions and stopping vomiting, and eliminating lumps and dispersing nodules. Pseudostellaria heterophylla is the tuber of the perennial herbaceous plant Pseudostomia heterophylla of the Caryophyllaceae family. It is sweet, slightly bitter and flat in nature and enters the spleen and lung meridians. It has the effects of replenishing qi and promoting body fluid. Glehnia littoralis is the root of the perennial herbaceous plant Coralleaf of the Umbelliferae family. It is sweet and slightly cold in nature and enters the lung and stomach meridians. It has the effects of clearing the lungs and nourishing yin, benefiting the stomach and promoting body fluid. Licorice is the root and rhizome of the perennial herbaceous plant Licorice of the Leguminosae family. It is sweet and flat in nature and enters the heart, lung, spleen and stomach meridians. It has the effects of replenishing spleen and qi, moistening lungs and relieving cough, relieving acute pain and alleviating medicinal properties.

[0026] According to the theory that "the esophagus is dominated by stomach qi", although the disease occurs in the esophagus, the basic pathogenesis is closely related to the stomach qi and the dysfunction of descending. Therefore, the treatment principle of GERD is still to promote descending and harmonize the stomach and restore the descending function of the stomach. The spleen and stomach function is closely related to the dredging of liver qi. Liver depression turns into heat, which goes against the stomach, and stomach qi carries heat upward, so heartburn, acid reflux and other discomforts occur. The treatment is to soothe the liver, regulate qi and purge heat, descend the adverse and harmonize the stomach, and thus formulate this prescription.

[0027] Formula design principle: Jinfeicao and Daizheshi in the formula are good at descending qi, especially descending stomach qi that goes up, and the two are combined as the main medicine. Coptis chinensis and Scutellaria baicalensis clear the stomach heat in the middle jiao, and Prunella vulgaris clears the liver fire that is stagnant, and they are the assistant medicines. Ganjiang is pungent and hot, warms the stomach and dispels cold, and assists the bitter and cold nature of Coptis chinensis and Scutellaria baicalensis; Pinellia ternata has the effect of descending adverse qi and stopping vomiting, and assists the main medicine in descending adverse qi and harmonizing the stomach; Cuttlebone restrains acid and harmonizes the stomach; Buddha's hand soothes the liver and regulates qi, and restores the function of liver qi and qi; Pseudostellaria chinensis replenishes qi and strengthens the spleen, and the spleen is naturally healthy and the liver does not offend the earth, which embodies the idea of ​​treating diseases before they occur "seeing liver diseases, knowing that the liver transmits to the spleen, and strengthening the spleen first"; Northern Adenophora nourishes yin and nourishes the stomach to prevent liver and stomach heat from consuming stomach yin, and the above are all adjuvants; Licorice harmonizes all the medicines, and is the guiding medicine. All the medicines are used together to play the effects of harmonizing the stomach, descending adverse qi, soothing the liver and purging heat.

[0028] Preferably, the Chinese medicine compound comprises the following raw materials in weight ratio:

[0029] Inula Britannica L.var chinensis (Rupr.) Reg, 8-12 copies

[0030] Ochre, Haematitum, 10-20 parts

[0031] Coptis chinensis Franch, 3-6 parts

[0032] Scutellaria baicalensis Georgi, 6-10 parts

[0033] Dried ginger, Zingiber officinale Rosc, 3-6 parts

[0034] Prunella vulgaris L, 10-15 parts

[0035] Buddha's hand, Citrus medica L.var.sarcodactylis Swingle, 6-10 servings

[0036] Cuttlebone, Sepiella maindroni de Rochebrune, 10-20 portions

[0037] Pinellia ternate (Thunb.) Breit., 6-10 portions

[0038] Pseudostellaria heterophylla (Miq.) Pax ex Pax et Hoffm., 10-20 parts Glehnia littoralis F. Schmidt ex Miq., 10-15 parts

[0039] Licorice, Glycyrrhiza uralensis Fisch., 3-6 parts.

[0040] Furthermore, the Chinese medicine compound is prepared from the extract of the raw materials as the active ingredient, and pharmaceutically acceptable excipients or auxiliary ingredients are added to form a commonly used pharmaceutical preparation.

[0041] As an example, the preparation is an oral preparation.

[0042] For example, the oral preparation is a tablet, capsule, pill, granule, oral liquid or decoction.

[0043] The second aspect of the present invention provides a method for preparing the Chinese medicine compound described in the first aspect, comprising: taking various raw materials according to a ratio, adding water and boiling to obtain the Chinese medicine compound.

[0044] Furthermore, after decocting with water, pharmaceutically acceptable excipients or auxiliary ingredients are added to prepare a commonly used pharmaceutical preparation.

[0045] For example, when decocting, 1500ml-4000ml of water is added to every 150g of total raw materials, and decocted into 200-400ml of liquid to obtain the Chinese herbal compound.

[0046] The third aspect of the present invention provides use of the Chinese herbal compound described in the first aspect in a drug for treating liver-stomach stagnation and heat syndrome of gastroesophageal reflux disease.

[0047] Compared with the prior art, the present invention has the following advantages:

[0048] The Chinese medicine compound for treating gastroesophageal reflux disease liver-stomach stagnation heat syndrome provided by the present invention can effectively improve clinical efficacy, alleviate the clinical symptoms of patients with gastroesophageal reflux disease liver-stomach stagnation heat syndrome, reduce gastroesophageal reflux disease questionnaire score (GerdQ score), promote endoscopic esophageal mucosal healing, reduce clinical recurrence of patients with gastroesophageal reflux disease liver-stomach stagnation heat syndrome, and prolong recurrence time. At the same time, the oral medication prepared by the Chinese medicine compound has a simple preparation method, small drug side effects, high safety, and improved patient compliance in terms of taking. Therefore, the present invention effectively overcomes various shortcomings in the prior art and has a high industrial utilization value. DETAILED DESCRIPTION

[0049] The present invention is further described below in conjunction with the examples. It should be understood that the examples are only used to further illustrate and explain the invention and are not used to limit the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present invention.

[0050] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0051] The compatibility of the present invention complies with the "monarch, minister, assistant and envoy" principle of traditional Chinese medicine. The following traditional Chinese medicines used in the present invention are compatible with each other and can exert their synergistic therapeutic effects. The various components of the traditional Chinese medicine raw materials used have mutually intertwined, mutually promoted and coordinated efficacy.

[0052] The raw materials (or medicinal materials) used in the present invention can be purchased from ordinary medical stores or Chinese medicinal materials sales companies, and their specifications meet the national medical standards or meet the relevant provisions of the Chinese Pharmacopoeia, etc. Unless otherwise specified, the medicinal materials used are all Chinese medicinal materials slices, which can also be obtained and processed.

[0053] The term "patient" as used herein refers to a person, wild animal, or domestic animal suffering from a disease. Wild animals are animals that are not artificially domesticated in their natural state. Domestic animals are animals that are artificially raised to provide a source of food, such as monkeys, apes, dogs, mice, hamsters, pigs, rabbits, horses, cows, buffaloes, bulls, sheep, and goats. The "patient" to be diagnosed is preferably a mammal, especially a human.

[0054] Example 1

[0055] Take 10g of Jinfeicao, 15g of Daizheshi, 3g of Coptis chinensis, 10g of Scutellaria baicalensis, 3g of Dry Ginger, 15g of Prunella vulgaris, 10g of Citron, 20g of Cuttlebone, 10g of Pinellia, 10g of Pseudostellaria pseudoginseng, 10g of Adenophora australis, and 5g of Licorice, mix them together, add to 3000ml of water, put into a decoction vessel, boil into 200ml liquid and bag it to obtain the desired drug preparation sample 1#.

[0056] Example 2

[0057] Take 10g of Jinfeicao, 15g of Daizheshi, 3g of Coptis chinensis, 10g of Scutellaria baicalensis, 3g of Dry Ginger, 15g of Prunella vulgaris, 10g of Citron, 20g of Cuttlebone, 10g of Pinellia, 10g of Pseudostellaria pseudoginseng, 10g of Adenophora australis, and 5g of Licorice, mix them together, add to 3000ml of water, put into a decoction vessel, boil into 300ml liquid and bag it to obtain the required drug preparation sample 2#.

[0058] Example 3

[0059] Take 10g of Jinfeicao, 15g of Daizheshi, 3g of Coptis chinensis, 10g of Scutellaria baicalensis, 3g of Dry Ginger, 15g of Prunella vulgaris, 10g of Citron, 20g of Cuttlebone, 10g of Pinellia, 10g of Pseudostellaria pseudoginseng, 10g of Adenophora australis, and 5g of Licorice, mix them together, add to 3000ml of water, put into a decoction vessel, boil into 400ml liquid and bag it to obtain the required drug preparation sample 3#.

[0060] Example 4

[0061] Take 8g of Jinfeicao, 10g of Daizheshi, 2g of Coptis chinensis, 3g of Scutellaria baicalensis, 3g of Dry Ginger, 10g of Prunella vulgaris, 3g of Citron, 10g of Cuttlebone, 5g of Pinellia, 10g of Pseudostellaria pseudoginseng, 10g of Adenophora australis, and 2g of Licorice, mix them together, add to 3000ml of water, put into a decoction vessel, boil into 200ml liquid and bag it to obtain the required drug preparation sample 4#.

[0062] Example 5

[0063] Take 12g of Jinfeicao, 30g of Daizheshi, 10g of Coptis chinensis, 10g of Scutellaria baicalensis, 10g of Dry Ginger, 15g of Prunella vulgaris, 10g of Citron, 30g of Cuttlebone, 10g of Pinellia, 30g of Pseudostellaria pseudoginseng, 15g of Adenophora australis, and 10g of Licorice, mix them together, add to 3000ml of water, put into a decoction vessel, boil into 200ml liquid and bag it to obtain the required drug preparation sample 5#.

[0064] Test 1

[0065] 60 patients were selected as the observation group and compared with the patients who were treated with oral rabeprazole enteric-coated tablets as the control group. The treatment course was 8 weeks. The observation group took the drug preparation sample 1# described in Example 1. The specific research methods and statistical results are as follows:

[0066] 1. Research Methods

[0067] 1.1 Source of cases: All cases were patients with gastroesophageal reflux disease in the Department of Gastroenterology and the Esophagitis Clinic of our hospital from January 2021 to March 2024.

[0068] 1.2 The Western medicine diagnostic criteria were formulated based on the consensus opinion on gastroesophageal reflux disease in China (Chinese Society of Gastroenterology. 2020 Chinese Expert Consensus on Gastroesophageal Reflux Disease [J]. Chinese Journal of Digestion, 2020, 40(10): 649-663.).

[0069] 1.2.1 Clinical symptoms

[0070] (1) Typical gastroesophageal reflux symptoms, including heartburn and regurgitation;

[0071] (2) Atypical symptoms of gastroesophageal reflux disease, including chest pain, upper abdominal pain, upper abdominal burning sensation, belching, etc.;

[0072] (3) Extraesophageal symptoms include cough, throat symptoms, asthma, tooth erosion, etc.

[0073] 1.2.2 Endoscopic examination confirmed the presence of esophageal mucosal inflammation. The esophageal inflammation grading standard was developed according to the Los Angeles classification (LA classification) of the 1994 World Congress of Gastroenterology (Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut, 1999, 45(2): 172-80.).

[0074] 1.3 TCM syndrome diagnosis criteria: Referring to the 2023 consensus of TCM diagnosis and treatment experts on gastroesophageal reflux disease, the liver-stomach stagnation and heat syndrome is manifested as: Main symptoms: ① heartburn; ② acid reflux. Secondary symptoms: ① burning pain behind the sternum; ② burning pain in the stomach; ③ abdominal distension; ④ belching or regurgitation; ⑤ irritability; ⑥ hunger. Tongue and pulse: ① red tongue with yellow fur; ② stringy pulse. The above two main symptoms plus two secondary symptoms, with reference to the tongue and pulse, can be used to diagnose the syndrome.

[0075] 1.4. Inclusion criteria

[0076] (1) Meet the Western medical diagnostic criteria for reflux esophagitis;

[0077] (2) Meet the TCM syndrome diagnostic criteria for reflux esophagitis with liver-stomach stagnation and heat syndrome;

[0078] (3) patients aged 18 to 60 years;

[0079] (4) Patients with first diagnosis;

[0080] (5) Sign the informed consent form.

[0081] 1.5 Exclusion criteria

[0082] (1) Patients with any of the following diseases: peptic ulcer, history of gastroesophageal and duodenal surgery, Zollinger-Ellison syndrome, primary esophageal motility disorders (such as achalasia, scleroderma, primary esophageal spasm), upper gastrointestinal malignant lesions, coronary heart disease, diabetes, drug-induced esophagitis and mental illness.

[0083] (2) Pregnant or lactating women.

[0084] (3) People with language barriers.

[0085] 1.6 Exclusion criteria and handling of dropout cases

[0086] 1.6.1 Elimination criteria

[0087] (1) Cases that do not meet the inclusion criteria.

[0088] (2) Those who have poor compliance during the research process and cannot follow the treatment plan for clinical research;

[0089] 1.6.2 Handling of dropout cases

[0090] 1.6.2.1 Cases that meet the inclusion criteria but fail to complete the study for some reason are considered dropout cases. Dropout cases include cases where the subject withdraws on his / her own or where the doctor determines that the subject has withdrawn:

[0091] (1) Cases with serious adverse events, complications, and special physiological changes that make it unsuitable to continue the study;

[0092] (2) Cases where the subjects voluntarily withdrew;

[0093] (3) Cases not treated as specified in the study protocol;

[0094] (4) Cases where the patient is missing for more than 3 consecutive days.

[0095] 1.6.2.2 If adverse reactions occur, they should be included in the adverse reaction statistics; those who drop out of the treatment due to ineffectiveness should be included in the efficacy analysis.

[0096] 1.7 Case Grouping

[0097] The formula rand() in EXCEL software was used to generate a random permutation table, and the random numbers generated in the table were sorted to generate random numbers. Setting: Random numbers 1 to 60 are the observation group; random numbers 61-120: the control group.

[0098] 1.8 Treatment

[0099] Observation group: The patients with gastroesophageal reflux disease and liver-stomach stagnation heat syndrome in the observation group took the pharmaceutical preparation sample 1# obtained in Example 1, twice a day, half an hour after a meal, 200 ml each time, for a course of 8 weeks. During the medication period, the diet should be light, and strong tea, coffee, milk tea, chocolate, fruit, spicy stimulation, and raw and cold food should be avoided.

[0100] Control group: the drug used in comparative example 1, rabeprazole enteric-coated tablets, is taken orally as in comparative example 1. At present, proton pump inhibitors are the first choice for gastroesophageal reflux disease patients. The control group of gastroesophageal reflux disease patients with liver and stomach stagnation heat syndrome, take rabeprazole enteric-coated tablets twice a day, half an hour before meals, 40 mg each time, for a course of 8 weeks. During the medication period, the diet should be light, and strong tea, coffee, milk tea, chocolate, fruit, spicy stimulation, and raw and cold food should be avoided.

[0101] 1.9 Observation indicators and efficacy assessment

[0102] 1.9.1 Observation indicators

[0103] 1.9.1.1 Clinical symptom scoring: According to the "Guidelines for Clinical Research of New Chinese Medicines" (Zheng Xiaoyu (chief editor). Guidelines for Clinical Research of New Chinese Medicines (Trial). China Medical Science and Technology Press [M], 2002: 134-35.), the patient's symptoms are divided into four levels: none, mild, moderate, and severe, and the severity of the symptoms is recorded as 0, 1, 2, and 3 points respectively. The scores are recorded by a dedicated person. 0 points: no symptoms; 1 point: the patient can only recall the symptoms after being reminded; 2 points: there are symptoms but they do not affect daily life; 3 points: symptoms affect daily life. The frequency of symptom occurrence is calculated based on the number of days in 1 week. The score of each symptom in a week is equal to the product of the symptom severity score and the symptom frequency. The total symptom score in a week is equal to the sum of the scores of each symptom. After the treatment, the efficacy before treatment, the 4th week, and the 8th week was evaluated.

[0104] 1.9.1.2 Gastroesophageal Reflux Disease Questionnaire Score (GerdQ score): Record each item before and after treatment and when relapse occurs, and calculate the GerdQ score.

[0105] 1.9.1.3 Relapse time and relapse rate: Follow-up for half a year after the 8-week treatment. For those who relapse within half a year, the relapse time and relapse rate will be recorded.

[0106] 1.9.1.4 Endoscopic esophageal mucosal inflammation: Repeat gastroscopy 2 months after the end of treatment.

[0107] 1.9.2 Efficacy determination

[0108] 1.9.2.1 Clinical efficacy assessment criteria: formulated with reference to the “Guiding Principles for Clinical Research of New Chinese Medicines”.

[0109] Recovery: clinical symptoms disappear, and symptom score decreases by ≥95%;

[0110] Markedly effective: clinical symptoms basically disappeared (although there were occasional symptoms, they disappeared quickly), and the symptom score decreased by 70% to 94%; Effective: clinical symptoms did not disappear, but were alleviated compared with before, and the symptom score decreased by 30% to 69%;

[0111] Ineffective: Clinical symptoms have not disappeared, the severity has not been alleviated, and the symptom score has decreased by <30%.

[0112] The calculation formula is: (score before treatment - score after treatment) / score before treatment × 100%

[0113] 1.9.2.2 Criteria for judging the efficacy of main symptoms: formulated with reference to the "Guidelines for Clinical Research of New Chinese Medicines". Clinical control: after the course of treatment, the symptoms disappear;

[0114] Markedly effective: After the treatment, the symptom grade is reduced by 2 levels;

[0115] Effective: After the treatment, the symptom grade is reduced by 1 level;

[0116] Invalid: Those who fail to meet the above standards.

[0117] 1.9.2.3 Criteria for determining the efficacy of endoscopic esophageal mucosal inflammation

[0118] Cured: Endoscopically, the esophageal mucosa was normal.

[0119] Markedly effective: Endoscopic esophageal mucosal inflammation did not disappear, and the difference in scores before and after treatment was 2 points.

[0120] Effective: Endoscopic esophageal mucosal inflammation did not disappear, and the difference in scores before and after treatment was 1 point.

[0121] Ineffective: Endoscopic esophageal mucosal inflammation did not disappear, and the score difference before and after treatment was 0 or negative.

[0122] 1.10 Statistical analysis

[0123] SPSS21.0 for Windows statistical software was used for statistical analysis. The measurement data in the statistical description were expressed as mean ± standard deviation. The independent sample t-test was used for those that met the normal distribution and variance homogeneity, and the non-parametric test was used for comparison if they did not meet the normal distribution and variance homogeneity. The chi-square test was used for the count data. All the tests were two-sided. The differences between the data were expressed as P values. P>0.05 indicated no statistical significance; P<0.05 indicated statistical significance.

[0124] 2. Statistical results

[0125] A total of 120 cases were included in this study, with 60 cases in each group. Their general conditions are shown in Table 1.

[0126] Dropout situation: patients with a treatment course of less than 2 weeks will be considered dropout cases, and dropout cases will not be included in the statistical results; patients with a treatment course of more than 2 weeks will be included in the statistical results. Among the cases observed in this study, the minimum treatment course was 3 weeks, so there were no dropout cases.

[0127] 2.1 Comparative analysis of general data

[0128] Table 1 Comparative analysis results of general data between the two groups

[0129]

[0130] Results: After statistical testing, there was no statistically significant difference in gender composition, age, and course of disease between the two groups (P>0.05), indicating that the general data of the treatment groups before treatment were comparable.

[0131] 2.2 Comparison of overall clinical efficacy between the two groups

[0132] Table 2 Comparison of overall clinical efficacy between the two groups (cases)

[0133]

[0134] Note: Compared with the control group, * P<0.05.

[0135] Results: The chi-square test showed that the clinical efficacy of the observation group was better than that of the control group, which was statistically significant (P<0.05).

[0136] 2.3 Comparison of efficacy of main and secondary symptoms between the two groups

[0137] Table 3 Comparison of efficacy of main symptoms and secondary symptoms between the two groups (cases)

[0138]

[0139]

[0140] Note: Compared with the control group, * P<0.05, ** P<0.01.

[0141] Results: The chi-square test showed that the observation group was significantly better than the control group in improving the main symptoms (acid reflux, heartburn, and retrosternal pain) and secondary symptoms (upper abdominal distension, belching, and upper abdominal pain) of gastroesophageal reflux disease (P<0.05).

[0142] 2.4 Comparison of Gastroesophageal Reflux Disease Questionnaire (GerdQ) scores between the two groups

[0143] Table 4 Comparison of GerdQ scores between the two groups

[0144]

[0145] Note: * Compared with before treatment, ** P < 0.01; # Compared with the control group, # P<0.05.

[0146] Results: According to nonparametric test, there was no statistically significant difference in GerdQ scores between the two groups before treatment (P>0.05). Compared with the control group, the observation group was superior to the control group in reducing GerdQ scores (P<0.05).

[0147] 2.5 Comparison of endoscopic efficacy between the two groups

[0148] Table 5 Comparison of improvement of esophageal mucosal inflammation in two groups of reflux esophagitis (cases)

[0149]

[0150] Note: * Compared with the control group, * P<0.05.

[0151] Results: The chi-square test showed that the observation group was superior to the control group in improving endoscopic esophageal mucosal inflammation (P<0.05).

[0152] 2.6 Comparison of recurrence rate and recurrence time between the two groups

[0153] Table 6 Comparison of recurrence rate and recurrence time between the two groups (cases)

[0154]

[0155] Note: * Compared with the control group, * P < 0.05; ** P<0.01.

[0156] Results: According to statistical analysis, the recurrence rate in the observation group was significantly lower than that in the control group (P<0.05), and the recurrence time was longer than that in the control group (P<0.01).

[0157] It can be seen that the observation group is significantly better than the control group in improving the clinical symptoms of patients with liver and stomach stagnation and heat syndrome of gastroesophageal reflux disease, GerdQ scale score, and promoting the healing of esophageal mucosal inflammation, and can significantly reduce the recurrence rate of clinical symptoms and prolong the recurrence time of patients. In summary, a Chinese medicine compound for treating liver and stomach stagnation and heat syndrome of gastroesophageal reflux disease provided by the present invention has good drug absorption, can effectively improve clinical efficacy, alleviate the clinical symptoms of patients with liver and stomach stagnation and heat syndrome of gastroesophageal reflux disease, reduce the questionnaire score of gastroesophageal reflux disease (GerdQ score), promote endoscopic healing of esophageal mucosa, reduce the clinical recurrence of patients with liver and stomach stagnation and heat syndrome of gastroesophageal reflux disease, and prolong the recurrence time. At the same time, the drug has small side effects, high safety, and in terms of taking, it improves patient compliance. Therefore, the present invention effectively overcomes various shortcomings in the prior art and has a high industrial utilization value.

Claims

1. A Chinese medicinal compound for treating gastroesophageal reflux disease with liver-stomach heat syndrome, characterized in that: The invention comprises the following raw materials in weight proportion: 8-12 parts of golden feicui, 10-30 parts of magnetite, 2-10 parts of coptis root, 3-10 parts of scutellaria root, 3-10 parts of dried ginger, 10-15 parts of selfheal, 3-10 parts of citron, 10-30 parts of cuttlebone, 5-10 parts of pinellia, 10-30 parts of pseudostellaria, 10-15 parts of northern adenophora and 2-10 parts of liquorice.

2. The Chinese medicinal compound according to claim 1, characterized in that: The invention comprises the following raw materials in weight ratio: 8-12 parts of jinfeicao, 10-20 parts of daizheshi, 3-6 parts of coptis root, 6-10 parts of scutellaria baicalensis, 3-6 parts of dried ginger, 10-15 parts of selfheal, 6-10 parts of citron, 10-20 parts of cuttlebone, 6-10 parts of pinellia, 10-20 parts of pseudostellaria, 10-15 parts of northern adenophora and 3-6 parts of liquorice.

3. The Chinese medicinal compound according to claim 2, characterized in that: The invention comprises the following raw materials in weight proportion: 10 parts of golden feicao, 15 parts of magnetite, 3 parts of coptis root, 10 parts of scutellaria root, 3 parts of dried ginger, 15 parts of selfheal, 10 parts of citron, 20 parts of cuttlebone, 10 parts of pinellia, 10 parts of pseudostellaria, 10 parts of northern adenophora, and 5 parts of liquorice.

4. The Chinese medicinal composition according to any one of claims 1 to 3, characterized in that: The Chinese medicine compound is prepared from the extract of the raw materials as the active ingredient, and pharmaceutically acceptable excipients or auxiliary ingredients are added to form a commonly used pharmaceutical preparation.

5. The Chinese medicinal compound according to claim 4, characterized in that: The preparation is an oral preparation.

6. The Chinese medicinal compound according to claim 5, characterized in that: The oral preparation is tablet, capsule, pill, granule, oral liquid or decoction.

7. A method for preparing the Chinese medicinal compound according to any one of claims 1 to 3, characterized in that: include: The raw materials are taken according to the proportion, added with water and boiled to obtain the traditional Chinese medicine compound.

8. The preparation method according to claim 7, characterized in that: include: The raw materials are taken according to the proportion, boiled in water, and then pharmaceutically acceptable excipients or auxiliary ingredients are added to prepare a commonly used pharmaceutical preparation.

9. Use of the Chinese medicinal compound according to any one of claims 1 to 3 in treating liver-stomach heat syndrome of gastroesophageal reflux disease.

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