Traditional Chinese medicine composition for gastroesophageal reflux disease, preparation, preparation method and application

Abstract

The invention relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for gastroesophageal reflux disease, a preparation, a preparation method and application. The traditional Chinese medicine composition is prepared from the following raw medicinal materials in parts by weight: 20 to 30 parts of radix bupleuri, 20 to 30 parts of rhizoma polygoni cuspidati, 10 to 15 parts of caulis bambusae in taeniam, 20 to 25 parts of ginger processed pinellia, 15 to 20 parts of fructus evodiae, 20 to 25 parts of rhizoma atractylodis macrocephalae, 15 to 20 parts of poria cocos, 10 to 20 parts of rhizoma cyperi, 10 to 15 parts of spica prunellae, 10 to 15 parts of venenum bufonis, 10 to 20 parts of wine-processed radix paeoniae alba, 10 to 15 parts of caragana sinica rehd, 10 to 15 parts of fructus chebulae and 10 to 15 parts of dens draconis. The preparation method comprises the following steps: weighing the traditional Chinese medicine composition according to the formula dosage, and then adding water for decoction to obtain a traditional Chinese medicine decoction; combining the traditional Chinese medicine decoction, filtering and concentrating to obtain traditional Chinese medicine extract; and adding auxiliary materials into the traditional Chinese medicine extract, and preparing by adopting a conventional preparation mode. All the monarch, minister, assistant and guide medicines are combined to well treat the gastroesophageal reflux disease.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and in particular relates to a traditional Chinese medicine composition, preparation, preparation method and application for gastroesophageal reflux disease. Background Art

[0002] Gastroesophageal reflux disease (GERD) is a common gastrointestinal motility disorder caused by excessive contact of the esophageal lumen with gastric juice, leading to clinical GERD and esophageal mucosal damage. Patients primarily present with symptoms such as acid reflux, heartburn, and retrosternal pain. The disease is very common in Western countries. With my country's rapid economic development, improved living standards, a shift toward Westernized lifestyles and diets, and an aging population, the prevalence of GERD has steadily increased, and recurrence is highly common. The goals of GERD treatment are to relieve symptoms, repair mucosal damage, improve quality of life, and prevent recurrence and complications.

[0003] Proton pump inhibitors (PPIs) are the preferred treatment for GERD. Severe and refractory GERD can be treated with endoscopic or surgical approaches. Current GERD treatments have the following main drawbacks: long treatment duration, high recurrence rate, the need for maintenance therapy, adverse reactions from long-term acid suppression, and refractory GERD that is ineffective with acid suppression. Traditional Chinese medicine formulas can alleviate these shortcomings of current Western medicine combined with surgical treatment. However, existing traditional Chinese medicine formulas often treat a single pathogenesis, neglecting the root causes of GERD and the causes of refractory GERD caused by multiple pathologies. Summary of the Invention

[0004] In view of the deficiencies in the prior art, the present invention provides a traditional Chinese medicine composition, preparation, preparation method and application for gastroesophageal reflux disease.

[0005] Specifically, the first aspect of the present invention provides a traditional Chinese medicine composition for gastroesophageal reflux disease, which is composed of the following medicinal materials: bupleurum, polygonum cuspidatum, bamboo shavings, pinellia ternata, evodia rutaecarpa, atractylodes macrocephala, poria, cyperus rotundus, selfheal, toad venom, white peony root with wine, gentian root, terminalia chebula fruit, and dragon tooth.

[0006] As a further illustration of the present invention, the traditional Chinese medicine composition is composed of the following medicinal materials in parts by weight: 20-30 parts of bupleurum, 20-30 parts of polygonum cuspidatum, 10-15 parts of bamboo shavings, 20-25 parts of pinellia ternata, 15-20 parts of evodia rutaecarpa, 20-25 parts of atractylodes macrocephala, 15-20 parts of poria, 10-20 parts of cyperus rotundus, 10-15 parts of selfheal, 10-15 parts of toad venom, 10-20 parts of white peony root with wine, 10-15 parts of gentian root, 10-15 parts of terminalia chebula, and 10-15 parts of dragon's tooth.

[0007] As a further illustration of the present invention, the traditional Chinese medicine composition is composed of the following medicinal materials in parts by weight: 25 parts of bupleurum, 25 parts of polygonum cuspidatum, 13 parts of bamboo shavings, 22 parts of pinellia ternata, 17 parts of evodia rutaecarpa, 23 parts of atractylodes macrocephala, 18 parts of poria, 15 parts of cyperus rotundus, 12 parts of selfheal, 12 parts of toad venom, 15 parts of white peony root with wine, 13 parts of gentian root, 13 parts of terminalia chebula, and 12 parts of dragon's tooth.

[0008] The second aspect of the present invention provides use of the above-mentioned traditional Chinese medicine composition in the preparation of a medicament for treating gastroesophageal reflux disease.

[0009] As a further illustration of the present invention, the dosage form of the drug for treating gastroesophageal reflux disease is an oral preparation, and the oral preparation is selected from any one of granules, tablets, capsules, powders, decoctions or pills.

[0010] A third aspect of the present invention provides a method for preparing a preparation for treating gastroesophageal reflux disease, comprising the following steps: S1. Weigh the above-mentioned Chinese medicine composition according to the dosage of the formula, then add 5-20 times the total weight of the above-mentioned Chinese medicine composition of water and boil it several times to obtain a Chinese medicine decoction; S2. The Chinese medicine decoctions obtained by multiple decoctions in step S1 are combined, filtered, and concentrated to a relative density of 1-1.2 to obtain a Chinese medicine extract; S3. Add clinically acceptable excipients to the traditional Chinese medicine extract obtained in step S2, and prepare it using a conventional preparation method to prepare a clinically acceptable traditional Chinese medicine preparation.

[0011] As a further illustration of the present invention, the Chinese medicine preparation is any one of granules, tablets, capsules, powders, decoctions or pills.

[0012] Bupleurum: Bitter and slightly cold in nature and flavor, it enters the Liver, Gallbladder, and Triple Burner meridians. It possesses properties that clear away heat and relieve exterior symptoms, soothe the liver and regulate qi, promote bile secretion and alleviate jaundice, and harmonize qi. It has a wide range of clinical applications, including for symptoms of exogenous infections, damp-heat in the liver and gallbladder, and qi stagnation and blood stasis. Understanding the nature, flavor, and meridian patterns of Bupleurum is key to understanding its medicinal properties. A thorough understanding of its bitter and slightly cold nature and flavor, as well as its meridian patterns, facilitates the correct selection of prescriptions and medications in clinical practice, maximizing the therapeutic effects of Bupleurum.

[0013] Polygonum cuspidatum: Bitter, sour, and slightly cold in nature. It enters the liver, gallbladder, and lung meridians. It has the effects of dispelling dampness and jaundice, clearing heat and detoxifying, dispersing blood stasis and relieving pain, and relieving cough and phlegm. It can remove jaundice caused by damp heat, treat amenorrhea, dissipate blood stasis in gynecological masses, and treat adnexitis and uterine fibroids. Polygonum cuspidatum can also be used to treat injuries from falls, coughs, and excessive phlegm, relieving coughs and reducing phlegm. However, it should be used with caution by pregnant women.

[0014] Bamboo Shavings: Sweet and slightly cold. It enters the Lung and Stomach meridians. It clears heat and resolves phlegm, relieves restlessness, and stops vomiting. It is suitable for treating hiccups and vomiting caused by stomach heat, stomach deficiency with heat, or the combined effects of phlegm and heat, stomach disharmony, and upward qi reflux. Roasting with ginger juice weakens its cooling properties and enhances its stomach-soothing and anti-vomiting effects. It is suitable for treating nausea and vomiting during pregnancy and fetal restlessness.

[0015] Ginger Pinellia: This is a processed product of raw Pinellia, with a pungent and warming nature. It enters the spleen, stomach, and lung meridians. It can relieve nausea and vomiting, warm the middle and resolve phlegm, and is used to treat phlegm and vomiting, and epigastric distension. Ginger Pinellia has pharmacological effects such as expectorant and antiemetic.

[0016] Atractylodes macrocephala: warm in nature, sweet and bitter in taste; enters the spleen and stomach meridians; effects: tonifies qi and strengthens the spleen, dries dampness and promotes diuresis, consolidates the exterior and stops sweating, and calms the fetus; used to treat symptoms such as spleen deficiency, fatigue, loss of appetite, and loose stools; eliminates edema, phlegm and other symptoms; treats spontaneous sweating due to exterior deficiency.

[0017] Evodia rutaecarpa: It has a bitter and hot nature and enters the liver, spleen, stomach, and kidney meridians. It dispels cold and relieves pain, relieves nausea and vomiting, and aids yang and relieves diarrhea, warming and unblocking the meridians.

[0018] Poria cocos: Sweet, mild, and neutral in nature; it enters the heart, lung, spleen, and kidney meridians. It can improve symptoms such as loss of appetite, abdominal distension, and loose stools caused by spleen deficiency and dampness, and is often used in combination with Atractylodes macrocephala and Chinese yam. It is particularly suitable for treating diarrhea and phlegm caused by spleen deficiency and dampness retention. For diarrhea caused by spleen deficiency, it is often combined with herbs such as Codonopsis pilosula, Atractylodes macrocephala, and Chinese yam to tonify the spleen and eliminate dampness. For dampness caused by spleen deficiency and phlegm retention, it is often combined with herbs such as Tangerine peel and Atractylodes macrocephala to tonify, strengthen the spleen, and eliminate dampness and resolve phlegm.

[0019] Cyperus rotundus: Pungent, slightly bitter, slightly sweet, and neutral in nature, it enters the Liver, Spleen, and Triple Burner meridians. Its benefits include soothing the liver and relieving depression, regulating qi and alleviating fullness, regulating menstruation, and relieving pain. It can be used to treat chest and flank pain, abdominal pain, and hernia pain caused by liver qi stagnation; it can also treat abdominal distension, fullness, and pain caused by spleen and stomach qi stagnation.

[0020] Prunella vulgaris: It is cold in nature, bitter and pungent in flavor, and enters the liver and gallbladder meridians. It clears liver fire and relieves stagnation. It is suitable for treating symptoms such as red and swollen eyes, eye pain, headaches, and dizziness caused by liver fire. It is also used to treat scrofula, phlegm nodules, goiters, and other conditions caused by stagnation of phlegm and fire. Modern research shows that Prunella vulgaris has antihypertensive, anti-tumor, anti-inflammatory, and immunosuppressive effects.

[0021] Toad venom: Pungent in flavor and cooling in nature, it enters the Liver and Spleen meridians. It has the effects of removing dead tissue, promoting tissue regeneration, and relieving toxins and pain. Because it is bitter and laxative, it can dredge the meridians, is suitable for both internal and external use, and is non-toxic, making it a common adjuvant in various traditional Chinese medicines. It can also be ground directly into a powder and applied to wounds to achieve detoxification and analgesic effects.

[0022] White Peony Root (Liquorice) has a bitter, sour, and sweet flavor and is slightly cold in nature. It enters the Liver and Spleen meridians. It has the effects of nourishing blood and regulating menstruation, calming the liver and relieving pain, warming the stomach and dispelling cold, consolidating yin and stopping sweating, promoting blood circulation and removing blood stasis, dredging the meridians, and calming liver yang. It also has anti-inflammatory properties, protects the digestive system, protects the cardiovascular system, enhances tolerance to hypoxia, provides antioxidant protection, prevents aging, relieves fatigue, boosts immunity, regulates the endocrine system, and has antibacterial and antiviral properties.

[0023] Terminalia chebula (Terminalia) fruit: Its properties are neutral, bitter, sour, and astringent. It enters the lung and large intestine meridians. It has lung-tonifying, cough-relieving, and diarrhea-relieving properties, and can be used to treat chronic diarrhea, dysentery, and lung deficiency-induced cough and asthma. It can be used in combination with herbs such as pomegranate peel and Poria cocos for the treatment of chronic diarrhea and dysentery.

[0024] Golden Sparrow Root: Pungent, bitter, and neutral in nature. It enters the Lung and Spleen meridians. It has the effects of clearing the lungs and tonifying the spleen, promoting blood circulation and unblocking the meridians, clearing away heat and detoxifying, reducing swelling and relieving pain, and promoting blood circulation and removing blood stasis. It is commonly used to treat conditions caused by heat, toxicity, and blood stasis. Golden Sparrow Root has excellent swelling and pain relief effects, and also has kidney-tonifying and yang-strengthening properties, making it suitable for treating symptoms such as soreness of the waist and knees, impotence, and spermatorrhea caused by kidney deficiency.

[0025] Dragon Teeth: Its properties are astringent, sweet, and cooling, primarily acting on the Heart and Liver meridians. Its primary benefits include calming the nerves, clearing heat and relieving restlessness, calming the liver and suppressing yang, and astringing and strengthening. Therefore, it can be used to treat symptoms such as mouth and tongue sores caused by excessive heart fire. It can be combined with coptis root and lotus seed heart to enhance its effects. Dragon Teeth also has yang-suppressing and astringent properties, as its calming properties help lower heart rate and promote a calm state of mind.

[0026] Traditional Chinese medicine doesn't have the term "gastroesophageal reflux disease." Medical texts throughout the ages have categorized and described the condition by symptoms. For example, Danxi's Heart Method states that food stagnation turning into heat can cause acid regurgitation: "Burping and acid regurgitation are caused by food stagnation and heat." Damp-heat stagnation in the liver can also cause acid regurgitation: "Acid regurgitation is caused by damp-heat accumulating in the liver and then escaping, lurking between the lungs and stomach." Suwen's Xuanjiyuanbingshi Liuqiweibing Acid Regurgitation states that "excessive fire suppresses metal and cannot pacify wood, resulting in excessive liver wood and acid regurgitation." The Yilin Shengmo Daquan states: "Acid regurgitation is caused by acid in the stomach attacking the upper body, causing it to overflow into the throat. The patient swallows it before being able to spit it out, and the sour taste pierces the heart, resembling acid regurgitation." "Jing Yue Quan Shu" records: "If the spleen and stomach are cold and weak, the middle qi is not healthy, and the three burners are bloated, it is qi deficiency and fullness in the middle. Its symptoms must be swallowing acid and belching, aversion to food and cold, or frequent loose stools, and there are no other signs of fire and fire pulses, it must be due to cold in the internal organs." It believes that cold and weak spleen and stomach can cause swallowing acid.

[0027] Modern physicians have different understandings of the pathogenesis of gastroesophageal reflux disease. The pathogenesis includes improper diet, emotional distress, and other factors that damage the liver and gallbladder, leading to imbalances in the liver and gallbladder's ability to regulate qi, dysfunction of the ascending and descending function of gastric qi, and upward flow of gastric qi to the esophagus and even the throat. Therefore, the above pathogenesis should be considered when conducting syndrome differentiation and treatment of gastroesophageal reflux disease. The present invention, while considering the imbalance in the liver and gallbladder's ability to regulate qi, also considers the root cause of the upward flow of gastric qi and the causes of emotional distress. This approach not only alleviates liver and gallbladder dysfunction, but also achieves the goal of treating all internal organs by clearing the lungs and relieving the heart. In the prescription, bupleurum, polygonum cuspidatum and bamboo shavings are the main drugs. Bupleurum and polygonum cuspidatum can soothe the liver and resolve blood stasis, dispel pathogenic qi and regulate qi. In addition, bamboo shavings can warm and nourish the gallbladder qi, harmonize the stomach and relieve restlessness, and can relieve the liver and gallbladder dysfunction and the gallbladder evil qi invading the spleen and stomach, which causes the stomach qi to go up; ginger pinellia, rutaecarpa, atractylodes macrocephala and poria are the assistant drugs. ginger pinellia and rutaecarpa can be used together to reduce adverse reactions and stop vomiting, boost yang and stop diarrhea. In addition, atractylodes macrocephala and poria can replenish qi and strengthen the spleen, remove dampness and resolve phlegm. The four drugs can be used together to regulate qi and regulate the pivot, regulate the spleen and harmonize the stomach; cyperus rotundus, herba scutellariae, toad venom and white peony root with wine are the adjuvant drugs. Cyperus rotundus and herba scutellariae can clear heat and dissipate blood stasis, and relieve pain. In addition, toad venom and white peony root with wine can calm the liver, soothe the meridians, relieve pain and improve chest pain and fullness. The four drugs can be used together to relieve the burning pain behind the sternum caused by liver qi stagnation; genus chinensis, terminalia chebula and dragon tooth are the guiding drugs. Goldenrod root and Terminalia chebula fruit clear the lungs and relieve cough, promote blood circulation and unclog the meridians, while dragon teeth clear away heat and relieve restlessness, calm the heart fire, ultimately achieving the effect of clearing the lungs and relieving the heart.

[0028] Compared with the prior art, the present invention has the following beneficial technical effects: In the prescription of the present invention, bupleurum, polygonum cuspidatum and bamboo shavings are the main drugs. Bupleurum and polygonum cuspidatum can soothe the liver and resolve blood stasis, dispel pathogenic qi and regulate qi. In addition, bamboo shavings can warm and nourish the gallbladder qi, harmonize the stomach and relieve restlessness, and can relieve the liver and gallbladder dysfunction and the stomach qi reflux caused by the gallbladder qi attacking the spleen and stomach; pinellia tuber, rutaecarpa, atractylodes macrocephala and poria are the assistant drugs. Pinellia tuber and rutaecarpa can be used together to reduce adverse reactions and stop vomiting, boost yang and stop diarrhea. In addition, atractylodes macrocephala and poria can replenish qi and strengthen the spleen, remove dampness and resolve phlegm. The four drugs can be used together to regulate qi and regulate the pivot, regulate the spleen and harmonize the stomach; cyperus rotundus, herba scutellariae, toad venom and white peony root with wine are the adjuvant drugs. Cyperus rotundus and herba scutellariae can clear heat and dissipate blood stasis, and relieve pain. In addition, toad venom and white peony root with wine can soothe the liver, dredge the meridians, relieve pain and improve chest pain and fullness. The four drugs can be used together to relieve the burning pain behind the sternum caused by liver qi stagnation; genus chinensis, terminalia chebula and dragon tooth are the guiding drugs. Goldenrod root and Terminalia chebula fruit clear the lungs and relieve cough, promote blood circulation and unclog the meridians, while dragon teeth clear away heat and relieve restlessness, calm the heart fire, ultimately achieving the effect of clearing the lungs and relieving the heart. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 These are HE staining images of esophageal tissues of rats in each group provided by the present invention, wherein (a) is the staining result of rats in the sham operation group, (b) is the staining result of rats in the model group, (c) is the staining result of rats in the positive group, (d) is the staining result of rats in the low-dose group of Example 1, (e) is the staining result of rats in the medium-dose group of Example 1, and (f) is the staining result of rats in the high-dose group of Example 1. DETAILED DESCRIPTION

[0030] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0031] Example 1 A traditional Chinese medicine composition for gastroesophageal reflux disease is composed of the following medicinal materials in parts by weight: 25 parts of bupleurum, 25 parts of polygonum cuspidatum, 13 parts of bamboo shavings, 22 parts of pinellia tuber, 17 parts of evodia rutaecarpa, 23 parts of atractylodes, 18 parts of poria, 15 parts of cyperus rotundus, 12 parts of selfheal, 12 parts of toad venom, 15 parts of white peony root with wine, 13 parts of gentian root, 13 parts of terminalia chebula fruit, and 12 parts of dragon's tooth.

[0032] Example 2 A traditional Chinese medicine composition for gastroesophageal reflux disease is composed of the following raw medicinal materials in parts by weight: 20 parts of bupleurum, 20 parts of polygonum cuspidatum, 10 parts of bamboo shavings, 20 parts of pinellia tuber, 15 parts of evodia rutaecarpa, 20 parts of atractylodes macrocephala, 15 parts of poria, 10 parts of cyperus rotundus, 10 parts of selfheal, 10 parts of toad venom, 10 parts of white peony root with wine, 10 parts of gentian root, 10 parts of terminalia chebula fruit, and 10 parts of dragon's tooth.

[0033] Example 3 A traditional Chinese medicine composition for gastroesophageal reflux disease is composed of the following raw medicinal materials in parts by weight: 30 parts of bupleurum, 30 parts of polygonum cuspidatum, 15 parts of bamboo shavings, 25 parts of pinellia tuber, 20 parts of evodia rutaecarpa, 25 parts of atractylodes macrocephala, 20 parts of poria, 20 parts of cyperus rotundus, 15 parts of selfheal, 15 parts of toad venom, 20 parts of white peony root with wine, 15 parts of gentian root, 15 parts of terminalia chebula fruit, and 15 parts of dragon's tooth.

[0034] Example 4 A traditional Chinese medicine composition for gastroesophageal reflux disease comprises 22 parts of bupleurum, 27 parts of polygonum cuspidatum, 12 parts of bamboo shavings, 23 parts of pinellia tuber, 18 parts of rutaecarpa, 22 parts of atractylodes, 17 parts of poria, 12 parts of cyperus rotundus, 13 parts of selfheal, 13 parts of toad venom, 17 parts of white peony root prepared with wine, 12 parts of gentian root, 12 parts of terminalia chebula fruit, and 13 parts of dragon's tooth.

[0035] Comparative Examples 1-6 all provide a traditional Chinese medicine composition, and the specific medicinal material composition and dosage of the traditional Chinese medicine composition of Comparative Examples 1-6 are detailed in Table 1 below.

[0036]

[0037] In the table, the names of Chinese medicines in brackets in the comparative examples respectively indicate that the Chinese medicine components are replaced with the same amount of the medicinal materials in brackets. For example, 25 （黄芪） It means that 25 parts of Polygonum cuspidatum are replaced by 25 parts of Astragalus membranaceus, and “—” means that the corresponding Chinese medicine component is not added to the Chinese medicine composition.

[0038] The medicinal materials in the above embodiments and comparative examples are all commercially available Chinese herbal medicine slices.

[0039] The Chinese medicine compositions provided in the above embodiments and comparative examples can be made into oral Chinese medicine preparations to verify their specific therapeutic effects on gastroesophageal reflux disease. The prepared drug dosage forms are oral preparations, such as granules, tablets, capsules, powders, decoctions or pills.

[0040] The oral preparation used in the following animal experiments is a granular preparation, and its specific preparation process is as follows: S1. Weigh the Chinese medicine composition provided in the above embodiments and comparative examples according to the dosage of the formula, then add 15 times the total weight of water of the above Chinese medicine composition and boil four times to obtain a Chinese medicine decoction.

[0041] S2. The Chinese medicine decoctions obtained by decocting the four times in step S1 are combined, filtered and concentrated to a relative density of 1.1 (60° C.) to obtain a Chinese medicine extract.

[0042] S3. Add dextrin (10% by weight of the total weight of the Chinese medicine composition) to the Chinese medicine extract obtained in step S2, and spray-dry to obtain a spray-dried powder.

[0043] S4. Add dextrin (20% by weight of the total weight of the granular preparation to be prepared) to the dry powder obtained in step S3 and mix well to prepare the final granular preparation.

[0044] Experimental example: 1. Animal experiments: 1.1 Experimental drugs and animals: Medicine: Omeprazole enteric-coated tablets, Harbin Pharmaceutical Group; granular preparation made from the traditional Chinese medicine formula provided in Example 1 and Comparative Examples 1-6 above.

[0045] Experimental animals: 120 SPF male rats (weight: 180-220 g) were purchased from the Experimental Animal Center of Heilongjiang University of Chinese Medicine. After purchase, the rats were placed under SPF conditions for 3 days for adaptation before the experiment.

[0046] 1.2 Drug administration and modeling: Grouping: 120 SPF male rats were randomly divided into the low-dose group of Example 1, the medium-dose group of Example 1, the high-dose group of Example 1, the high-dose groups of Comparative Examples 1-6, a positive control group, a sham-operated group, and a model group.

[0047] Modeling: All the rats were fasted for 12 hours before surgery and anesthetized by intraperitoneal injection of sodium pentobarbital at a dose of 40 mg / kg rat body weight, and then the hair around the upper abdomen of the rats was removed.

[0048] Rats in the sham-operated group were secured to the operating table. The surgical area was disinfected after hair removal, and the stomach was removed through laparotomy. The surrounding ligaments and fascia of the gastric body were dissected, and the left gastric artery was ligated. After a 3-minute rest, the stomach was returned to the abdominal cavity. Penicillin sodium was injected intraperitoneally, and the abdominal viscera were moistened with sodium chloride. The abdomen was then closed. For 24 hours after surgery, the rats were deprived of food but not water. Subsequently, small amounts of feed were gradually introduced daily. Each rat was intraperitoneally injected with 40,000 units of penicillin sodium per day. After one to two weeks of observation and normalization, the treatment was discontinued.

[0049] Rats in all groups except the sham-operated group were secured to the operating table. The surgical area was disinfected after hair removal, and the abdomen was opened. A hemiduodenal ligation combined with a cardia muscle tear was performed. The stomach was then removed, the surrounding ligaments and fascia of the gastric body were dissected, and the branches of the left gastric artery crossing the cardia muscle were ligated, avoiding the vagus nerve in the anterior esophagus. Blunt dissection was performed longitudinally above the cardia, leaving a separation of approximately 1 cm and completely exposing the white mucosal layer to enhance reflux of gastric digestive fluid into the esophagus. The viscera were repositioned, and penicillin sodium was injected intraperitoneally. The abdominal organs were moistened with sodium chloride, and the abdomen was closed. Food and water were withheld for 24 hours after surgery. Feed was then gradually increased daily in small amounts. Each rat was intraperitoneally injected with 40,000 units of penicillin sodium daily. After one to two weeks of observation and normalization, the treatment was discontinued.

[0050] Administration: After the rats in each group were normalized, oral administration was initiated once daily for 14 consecutive days. The doses administered to each group were as follows: Example 1 low-dose group: 0.25 g / kg of Example 1 Chinese herbal granules dissolved in 0.4 mL of normal saline; Example 1 medium-dose group: 0.5 g / kg of Example 1 Chinese herbal granules dissolved in 0.4 mL of normal saline; Example 1 high-dose group: 1 g / kg of Example 1 Chinese herbal granules dissolved in 0.4 mL of normal saline. Comparative Examples 1-6 high-dose groups: 10 g / kg of Example 1-6 Chinese herbal granules dissolved in 0.4 mL of normal saline. Positive control group: 5 mg / kg of omeprazole enteric-coated tablets dissolved in 0.4 mL of normal saline. Sham and model groups: 0.4 mL of normal saline.

[0051] 1.3 Observation indicators: Detection of pH value of the lower esophagus: After anesthetizing the rats, a pH electrode was inserted into the lower esophagus to detect the pH value of the lower esophagus.

[0052] Serum indicators: Blood was collected from the abdominal artery and centrifuged to prepare serum. The levels of TNF-α, IL-6 and 5-HT in serum were detected by ELISA.

[0053] HE staining of esophageal tissue: about 2 cm long esophageal tissue was cut from the cardia to the oral cavity to prepare paraffin sections. The prepared paraffin sections of esophageal tissue were washed in xylene solution, ethanol and pure water in sequence, and then stained in hematoxylin solution for 8 minutes to wash away the floating color. Then, they were differentiated with color separation solution, stained with anti-blue solution and dehydrated by ethanol immersion, and then stained with eosin staining solution for 2 minutes. The sections were placed in anhydrous ethanol for dehydration and cleaning. After soaking in xylene solution, neutral gum was added to the center of the section. After the xylene evaporated, coverslips were added to seal the sections.

[0054] Pathological scoring: The above-mentioned hematoxylin-eosin staining was followed by neutral gum sealing and observation under an optical microscope for analysis and reading. The comprehensive pathological damage of the esophagus of rats in each group was evaluated according to the following criteria: squamous epithelial hyperplasia: none - 0 point, mild - 1 point, moderate - 2 points, severe - 3 points; keratinization and thickening: none - 0 point, mild - 1 point, moderate - 2 points, severe - 3 points; papillary extension of the lamina propria mucosa: none - 0 point, mild - 1 point, moderate - 2 points, severe - 3 points; inflammatory cell infiltration in the epithelial layer: none - 0 point, mild - 1 point, moderate - 2 points, severe - 3 points.

[0055] 1.4 Statistical methods: The measurement data were tested with t test, and the enumeration data were tested with χ test. 2 All measurement data were tested using ( ) indicated that SPSS 17.0 statistical software was used for data processing.

[0056] 1.5 Experimental Results 1.5.1 Comparison of pH levels in the lower esophagus of rats in each group.

[0057]

[0058] Note: Compared with the sham operation group, # P<0.05, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01; compared with the high-dose group in Example 1, ∆ P<0.05, ∆∆ P<0.01(n=10).

[0059] It can be seen from Table 2 that, relative to the sham-operated rats, the pH value of the lower esophagus of the model group rats was significantly reduced and acidic; relative to the model group rats, the pH value of the lower esophagus of the positive group, the low-dose group, the medium-dose group and the high-dose group of Example 1 was significantly increased, and the pH level of the rats in the high-dose group of Example 1 was close to that of the rats in the sham-operated rats, indicating that the Chinese medicine composition provided by the present invention can significantly improve the gastroesophageal acid reflux problem in rats. In addition, compared with the high-dose group of comparative examples 1-6, the increase in the pH value of the lower esophagus of the rats in the high-dose group of Example 1 of the present application was more obvious, and the difference was statistically significant, indicating that the Chinese medicine preparation provided by the present application has a better effect on improving the gastroesophageal acid reflux problem in rats than the Chinese medicine preparation provided by comparative examples 1-6, and also indicating that the monarch, minister, assistant and guiding medicines in the Chinese medicine composition provided by the present invention each perform their duties, cooperate with each other and are indispensable.

[0060] 1.5.2 Comparison of serum index levels among rat groups.

[0061]

[0062] Note: Compared with the sham operation group, # P<0.05, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01; compared with the high-dose group in Example 1, ∆ P<0.05, ∆∆ P<0.01(n=10).

[0063] As can be seen from Table 3, compared with the rats in the model group, the levels of TNF-α, IL-6 and 5-HT in the serum of the rats in the positive group, the low-dose group, the medium-dose group and the high-dose group of Example 1 were significantly reduced, indicating that the Chinese medicine composition provided by the present invention can effectively improve the levels of TNF-α, IL-6 and 5-HT in the serum of rats. The levels of TNF-α and IL-6 can indicate that the Chinese medicine preparation provided by the present invention has a good effect on improving inflammation, and the level of 5-HT can indicate that the Chinese medicine preparation provided by the present invention has a good effect on improving the central nervous system, that is, the Chinese medicine preparation provided by the present invention can regulate the emotions of rats to a certain extent. In addition, compared with the high-dose groups of comparative examples 1-6, the levels of TNF-α, IL-6 and 5-HT in the serum of rats in the high-dose group of Example 1 of the present application were more significantly reduced, and the improvement effects of the high-dose groups of comparative examples 1-6 were compared with those of the high-dose group of Example 1 of the present application. The difference was statistically significant, indicating that the Chinese medicine preparation provided by the present application is better than the Chinese medicine preparation provided by comparative examples 1-6 in improving the levels of TNF-α, IL-6 and 5-HT in rat serum, and also indicates that the monarch, minister, adjuvant and guiding medicines in the Chinese medicine composition provided by the present invention each perform their respective functions, cooperate with each other, and are indispensable.

[0064] 1.5.3 Comparison of pathological tissues of rats in each group.

[0065] Figure 1 HE staining of esophageal tissues of rats in the sham-operated group, model group, positive group, and low, medium, and high-dose groups of Example 1 is shown. As can be seen from the figure, the esophageal tissue structure of rats in the sham-operated group is basically intact, the mucosal epithelial cell morphology is basically normal, the structure is clear, and there is basically no inflammatory cell infiltration. Esophageal squamous cell hyperplasia is visible in the esophageal tissue of rats in the model group, papillary protrusions are present in the mucosal lamina propria, and some inflammatory cell infiltration is visible. Compared with the rats in the model group, the esophageal squamous cell hyperplasia of rats in the positive group and low, medium, and high-dose groups of Example 1 is reduced, the papillary protrusions in the mucosal lamina propria are reduced, and the inflammatory cell infiltration is significantly alleviated.

[0066]

[0067] Note: Compared with the sham operation group, # P<0.05, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01; compared with the high-dose group in Example 1, ∆ P<0.05, ∆∆ P<0.01(n=10).

[0068] As can be seen from Table 4, compared with the sham-operated rats, the esophageal tissue pathology scores of the model group rats were significantly higher, and compared with the model group rats, the esophageal tissue pathology scores of the rats in the positive group, the low-dose group, the medium-dose group and the high-dose group of Example 1 were significantly reduced, indicating that the Chinese medicine composition provided by the present invention can effectively improve the esophageal tissue of rats and has a significant improvement effect on the esophageal tissue lesions caused by gastroesophageal reflux. In addition, compared with the high-dose group of comparative examples 1-6, the esophageal tissue pathology scores of the rats in the high-dose group of Example 1 of the present application were more significantly reduced, and the difference was statistically significant, indicating that the Chinese medicine preparation provided by the present application is better than the Chinese medicine preparation provided by comparative examples 1-6 in improving the esophageal tissue lesions in rats, and also indicating that the monarch, minister, assistant and envoy medicines in the Chinese medicine composition provided by the present invention each perform their duties, cooperate with each other and are indispensable.

[0069] From the above analysis, compared with comparative examples 1-6, whether replacing or removing the two components of Polygonum cuspidatum and Rhizoma Anemarrhenae in the monarch medicine of this application will significantly reduce the effect of the Chinese medicine composition. In addition, removing some of the synergistic ministerial medicines, adjuvant medicines or guiding medicines will also reduce the effect of the Chinese medicine composition. It can be seen that the monarch, ministerial, adjuvant and guiding medicines in this application complement each other and are an indispensable part of the Chinese medicine formula. The lack or replacement of part of the Chinese medicine formula cannot achieve the best effect in treating gastroesophageal reflux disease in rats.

[0070] 2. Clinical trials 2.1 Case Source Eighty patients diagnosed with gastroesophageal reflux disease (GERD) were enrolled from outpatient and inpatient settings at the First Affiliated Hospital of Heilongjiang University of Chinese Medicine between June 1, 2024, and December 31, 2024. They were randomly assigned to a treatment group (25 males and 15 females) in a 1:1 ratio using a stratified randomization method. The treatment group consisted of 40 patients (25 males and 15 females, with a mean age of (55.2±6.4) years). The control group consisted of 40 patients (26 males and 14 females, with a mean age of (53.6±5.7) years). Statistical analysis showed no significant differences in the distribution of general information between the two groups (P>0.05), indicating comparability between the two groups.

[0071] 2.2 Diagnostic criteria The following Western medical diagnostic criteria were developed with reference to the "Chinese Expert Consensus on Gastroesophageal Reflux Disease (2014)": ① Reflux and heartburn are typical symptoms, with atypical symptoms such as chest pain, upper abdominal pain, upper abdominal burning, and belching; other symptoms caused by gastroesophageal reflux, such as dysphagia, sore throat, and bitter taste in the mouth, may also be present; ② Gastroscopy: presence of esophagitis (the severity of esophagitis is graded using the Los Angeles classification), or no microscopic esophageal inflammation, but pathological acid reflux is confirmed by 24-hour pH-impedance testing.

[0072] With reference to the "Consensus on the Diagnosis and Treatment of Gastroesophageal Reflux Disease in Traditional Chinese Medicine (2009)," the following TCM symptom diagnostic criteria have been established: Primary symptoms: bitter taste in the mouth and dry throat; heartburn. Secondary symptoms: burning pain behind the sternum; chest and back pain; acid reflux; belching; irritability; frequent nausea and vomiting; red tongue with a yellow, greasy coating and a wiry, slippery pulse. Syndrome determination criteria: The primary symptom is essential; the addition of two or more secondary symptoms confirms the diagnosis.

[0073] Inclusion criteria: ① Age between 18 and 70 years old. ② Meet the above-mentioned Western and Traditional Chinese Medicine diagnostic criteria. ③ Voluntarily and actively cooperate with the trial and sign the informed consent form.

[0074] Exclusion criteria: ① Pregnant or lactating women and disabled patients; ② Patients with a history of severe organic and mental illness, such as cardiovascular and cerebrovascular diseases, liver and kidney diseases, blood-related diseases, and mental illness; ③ Patients with other digestive system diseases other than gastroesophageal reflux disease, such as hiatal hernia, peptic ulcer, intestinal obstruction, etc.; ④ Patients who are allergic or may be allergic to the components of this trial drug.

[0075] 2.3 Treatment methods The Chinese medicine composition formula provided in Example 1 was used. Referring to the Chinese Pharmacopoeia (2020 edition) method for preparing Chinese medicine granules, the pharmaceutical factory of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine prepared bagged Chinese medicine granules. Each bag contained 10 g of the crude drug, which constituted the Chinese medicine granules for the treatment group. The control group received omeprazole enteric-coated tablets. Both groups took the drug twice daily, with the treatment group receiving one bag (containing 10 g of the crude drug) and the control group receiving 20 mg each time, for 8 consecutive weeks.

[0076] 2.4 Efficacy evaluation criteria 2.4.1 TCM symptom efficacy evaluation criteria: Symptom Grading: Referring to the efficacy assessment criteria in the 2017 "Consensus on the Diagnosis and Treatment of Gastroesophageal Reflux Disease with Integrated Traditional Chinese and Western Medicine," all symptoms are categorized into four levels: none, mild, moderate, and severe. Primary and secondary symptoms are scored as 0 (no symptoms), 1 (mild symptoms with no impact on daily life), 2 (moderate symptoms with some impact on daily life), and 3 (severe symptoms with significant impact on daily life). Primary symptoms include acid reflux and heartburn. Secondary symptoms include loss of appetite, fatigue, loose bowel movements, and cold hands and feet. Symptom efficacy is evaluated using the percentage of symptom improvement, calculated as [(pre-treatment score - post-treatment score) / pre-treatment score] × 100%.

[0077] Symptom efficacy assessment criteria: Refer to the "Consensus on the Diagnosis and Treatment of Gastroesophageal Reflux Disease by Traditional Chinese and Western Medicine" (2017): Cured: Symptoms essentially disappear (efficacy index above 95%). Markedly effective: Symptoms significantly improved (efficacy index 70%-95%). Effective: Symptoms significantly improved (efficacy index 30%-70%). Ineffective: No improvement or worsening of symptoms (efficacy index below 30%).

[0078] Total effective rate = cure rate + marked effective rate + effective rate.

[0079] 2.4.2 Western medicine efficacy evaluation standards: Endoscopic efficacy assessment criteria: Endoscopic LA grading is determined based on the degree of esophageal mucosal damage and improvement in inflammation observed before and after treatment during a re-endoscopic gastroscopy. The grading is based on four levels: cured, markedly effective, effective, and ineffective. Cured: The esophageal mucosa returns to normal. Markedly effective: The esophageal mucosal grading improves by two levels, with significant improvement in congestion and erosion. Effective: The esophageal mucosal grading improves by one level, with reduced congestion and erosion. Ineffective: The esophageal mucosal grading does not improve, with congestion and erosion remaining unchanged or even worsening.

[0080] 2.5 Statistical methods The measurement data were tested with t test, and the enumeration data were tested with χ test. 2 All measurement data were tested using ( ) indicated that SPSS 17.0 statistical software was used for data processing.

[0081] 2.6 Experimental Results

[0082] Note: Compared with the control group, * P<0.05.

[0083]

[0084] Note: Compared with the control group, * P<0.05.

[0085] It can be seen from Tables 5 and 6 that in the results of the TCM symptom efficacy evaluation, the total effective rate of the treatment group was 92.5%, and the total effective rate of the control group was 62.5%; in the results of the gastroscopy efficacy evaluation, the total effective rate of the treatment group was 92.5%, and the total effective rate of the control group was 75.0%; and regardless of the results of the TCM symptom efficacy evaluation or the Western medicine gastroscopy symptom efficacy evaluation, the clinical efficacy of the treatment group was significantly better than that of the control group, and the difference was statistically significant, indicating that the clinical efficacy of the Chinese medicine composition provided in this application is better than that of traditional Western medicine and has certain clinical advantages.

[0086] It should be noted that, in this document, terms such as "comprises", "includes" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or apparatus that includes a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements that are inherent to such process, method, article or apparatus.

[0087] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A Chinese medicine composition for gastroesophageal reflux disease, characterized in that: The traditional Chinese medicine composition is composed of the following medicinal materials: bupleurum, polygonum cuspidatum, bamboo shavings, pinellia tuber, evodia rutaecarpa, atractylodes macrocephala, tuckahoe, cyperus rotundus, selfheal, toad venom, white peony root with wine, genus bronchus, terminalia chebula fruit and dragon tooth.

2. The Chinese medicine composition for gastroesophageal reflux disease according to claim 1, characterized in that The traditional Chinese medicine composition is composed of the following medicinal materials in parts by weight: 20-30 parts of bupleurum, 20-30 parts of polygonum cuspidatum, 10-15 parts of bamboo shavings, 20-25 parts of pinellia tuber, 15-20 parts of evodia rutaecarpa, 20-25 parts of atractylodes macrocephala, 15-20 parts of poria, 10-20 parts of cyperus rotundus, 10-15 parts of selfheal, 10-15 parts of toad venom, 10-20 parts of white peony root with wine, 10-15 parts of gentian root, 10-15 parts of terminalia chebula fruit, and 10-15 parts of dragon's tooth.

3. The Chinese medicine composition for gastroesophageal reflux disease according to claim 1, characterized in that The traditional Chinese medicine composition is composed of the following medicinal materials in parts by weight: 25 parts of bupleurum, 25 parts of polygonum cuspidatum, 13 parts of bamboo shavings, 22 parts of pinellia tuber, 17 parts of evodia rutaecarpa, 23 parts of atractylodes, 18 parts of tuckahoe, 15 parts of cyperus rotundus, 12 parts of selfheal, 12 parts of toad venom, 15 parts of white peony root with wine, 13 parts of gentian root, 13 parts of terminalia chebula fruit and 12 parts of dragon's tooth.

4. Use of the traditional Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for treating gastroesophageal reflux disease.

5. The use according to claim 4, characterized in that The dosage form of the drug for treating gastroesophageal reflux disease is an oral preparation, and the oral preparation is selected from any one of granules, tablets, capsules, powders, decoctions or pills.

6. A method for preparing a traditional Chinese medicine composition for treating gastroesophageal reflux disease, characterized in that: The following steps are involved: S1. Weigh the Chinese medicine composition provided by claim 2 or 3 according to the dosage of the formula, then add 5-20 times the total weight of the Chinese medicine composition of water and boil it several times to obtain a Chinese medicine decoction; S2. The Chinese medicine decoctions obtained by multiple decoctions in step S1 are combined, filtered, and concentrated to a relative density of 1-1.2 to obtain a Chinese medicine extract; S3. Add clinically acceptable excipients to the traditional Chinese medicine extract obtained in step S2, and prepare it using a conventional preparation method to prepare a clinically acceptable traditional Chinese medicine preparation.

7. The method for preparing the preparation for treating gastroesophageal reflux disease according to claim 6, wherein: The Chinese medicine preparation is any one of granules, tablets, capsules, powders, decoctions or pills.

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