Traditional Chinese medicine composition and traditional Chinese medicine granules for treating liver-stomach disharmony type reflux esophagitis

Abstract

The invention belongs to the field of traditional Chinese medicine compositions, and relates to a traditional Chinese medicine composition and traditional Chinese medicine granules for treating liver-stomach disharmony type reflux esophagitis, and the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 6-12 parts of pericarpium citri reticulatae viride, 6-12 parts of pericarpium citri reticulatae, 6-12 parts of moutan bark, 5-10 parts of cortex magnoliae officinalis and 6-12 parts of cortex fraxini. The traditional Chinese medicine is prepared from 5-10 parts of calcined concha arcae, 5-10 parts of cuttle bone, 3-9 parts of ginger, 5-10 parts of sandalwood, 8-15 parts of salvia miltiorrhiza, 8-15 parts of calcined oyster, 5-10 parts of immature bitter orange, 5-9 parts of oven earth and 8-15 parts of concha meretricis seu cyclinae. The traditional Chinese medicine composition takes green tangerine peel, immature bitter orange, calcined concha arcae and cuttle bone as monarch drugs; pericarpium citri reticulatae, cortex magnoliae officinalis, calcined oyster shell, concha meretricis seu cyclinae, sandalwood, cortex moutan and cortex fraxini are taken as Salvia miltiorrhiza, oven earth and ginger are used as adjuvant drugs. The traditional Chinese medicine composition treats reflux by soothing liver-qi stagnation and regulating qi and harmonizing stomach to regulate qi activity and calming adverse-rising energy and controlling acid, is assisted by clearing heat and dispersing blood stasis to remove heat stasis and blood stasis, can warm middle and harmonize stomach and protect mucous membrane, can achieve a good treatment effect by single medication, and has the advantages of quick response, stable curative effect, high total effective rate, low recurrence rate and the like.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine compositions, and more particularly to a traditional Chinese medicine composition and traditional Chinese medicine granules for treating liver-stomach disharmony type reflux esophagitis. Background Art

[0002] Reflux esophagitis (RE), also known as gastroesophageal reflux disease (GERD), is caused by damage to the esophageal mucosa due to factors such as decreased esophageal anti-reflux function, reduced esophageal clearance, and a weakened esophageal mucosal barrier. This disease is often accompanied by abnormalities of the lower esophageal sphincter and structural changes at the gastroesophageal junction, such as hiatal hernia. These weaken the anti-reflux mechanism, making it easier for gastric contents to reflux. Common symptoms include reflux and heartburn, chest pain, upper abdominal pain, burning sensation, and belching. Some patients also experience symptoms of indigestion.

[0003] The incidence of reflux esophagitis (RE) in China has been increasing annually. Among the general population, the prevalence is approximately 10%-20%. The incidence is higher in urban areas than in rural areas due to factors such as high work pressure, irregular diet, and prolonged sitting. Reflux esophagitis is categorized in Traditional Chinese Medicine as liver-stomach heat stagnation syndrome, liver-stomach disharmony syndrome, spleen deficiency and stomach heat syndrome, spleen deficiency and qi stagnation syndrome, and qi deficiency and blood stasis syndrome. Liver-stomach disharmony syndrome is the most common symptom among reflux esophagitis patients, especially in those aged 20-50.

[0004] Commonly used medications for reflux esophagitis include omeprazole, pantoprazole, cimetidine, nizatidine, and domperidone. However, these medications are primarily symptomatic, with low overall efficacy rates, high recurrence rates, and significant side effects. Traditional Chinese medicine prescriptions such as Zuojin Wan (Zuojin Wan) are known to clear the liver and relieve heat, reduce adverse reactions, and relieve vomiting. They are used to treat symptoms of liver-fire attacking the stomach, characterized by flank pain, vomiting, bitter taste in the mouth, and noisy, acid-regurgitating stomach. Currently, they are primarily used for acute and chronic gastritis, gastric ulcers, and other conditions characterized by liver-fire attacking the stomach. Modified Zuojin Wan (Jiawei Zuojin Wan) adds Chuandongzi (Chuandongzi) to regulate qi and relieve pain, Cyperus rotundus to soothe the liver and regulate qi, Pinellia ternata to reduce adverse reactions and relieve vomiting, Tangerine peel to regulate qi and strengthen the spleen, ginger to warm the middle and stop vomiting, Poria cocos to strengthen the spleen and harmonize the stomach, White Peony Root to soften the liver and nourish liver blood, and Licorice root to strengthen the spleen and stomach and alleviate liver urgency, thus harmonizing the various herbs. The entire prescription works together to clear the liver and harmonize the stomach, clearing liver fire and reducing stomach qi. Jiawei Zuojin Wan, combined with rabeprazole sodium enteric-coated capsules and domperidone tablets, has shown excellent efficacy in treating reflux esophagitis, with an overall efficacy rate of 95.5%. However, Jiawei Zuojin Wan is bitter and cold, and prolonged use can damage the spleen and stomach's yang energy. Rabeprazole can also cause gastrointestinal discomfort with long-term use, and the three-drug combination requires frequent and high doses. Therefore, there is a need for a traditional Chinese medicine combination that is effective in treating reflux esophagitis characterized by liver-stomach disharmony without the need for combined Western medication. Summary of the Invention

[0005] In view of the shortcomings and deficiencies of the prior art, the present invention aims to provide a Chinese medicine composition for treating reflux esophagitis of the liver-stomach disharmony type. This Chinese medicine composition contains qinpi and moutan bark, which clear away heat without causing excessive cold, and zaoxintu, combined with ginger, can improve the dull pain in the stomach and loose stools caused by long-term use of bitter and cold medicines. The combined use of calcined corrugated seeds, cuttlefish bone, calcined oyster shell, and sea clam shell has a calcium carbonate content of over 60%, neutralizing gastric acid 2-3 times that of a single drug. Furthermore, the amino acid components of cuttlefish bone and calcined oyster shell can promote the secretion of epidermal growth factor and accelerate mucosal healing, making it more suitable for long-term use. Based on years of clinical experience, this Chinese medicine composition has been shown to achieve good therapeutic effects when used alone. It has the advantages of rapid onset, stable efficacy, high total efficacy, and low recurrence rate in the treatment of reflux esophagitis of the liver-stomach disharmony type.

[0006] To achieve the above object, the present invention adopts the following technical solutions: A traditional Chinese medicine composition for treating reflux esophagitis of liver-stomach disharmony type is prepared from the following raw materials in parts by weight: 6-12 parts of green peel, 6-12 parts of dried tangerine peel, 6-12 parts of moutan bark, 5-10 parts of magnolia bark, 6-12 parts of qinpi, 5-10 parts of calcined citrus fruit, 5-10 parts of cuttlefish bone, 3-9 parts of ginger, 5-10 parts of sandalwood, 8-15 parts of salvia miltiorrhiza, 8-15 parts of calcined oyster shell, 5-10 parts of immature bitter orange, 5-9 parts of stove core soil, and 8-15 parts of sea clam shell.

[0007] As a preferred embodiment of the present invention, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 6-12 parts of green peel, 10-12 parts of dried tangerine peel, 8-12 parts of moutan bark, 7-10 parts of magnolia bark, 10-12 parts of qinpi, 6-10 parts of calcined corrugated fruit, 8-10 parts of cuttlefish bone, 5-9 parts of ginger, 6-10 parts of sandalwood, 10-15 parts of salvia miltiorrhiza, 10-15 parts of calcined oyster shell, 6-10 parts of citrus aurantium, 7-9 parts of stove core soil, and 10-15 parts of sea clam shell.

[0008] As a preferred embodiment of the present invention, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 10-12 parts of green peel, 10-12 parts of dried tangerine peel, 8-10 parts of moutan bark, 7-8 parts of magnolia bark, 10-12 parts of qinpi, 8-10 parts of calcined corrugated paper, 8-10 parts of cuttlefish bone, 8-9 parts of ginger, 8-10 parts of sandalwood, 10-15 parts of salvia miltiorrhiza, 12-15 parts of calcined oyster shell, 6-10 parts of citrus aurantium, 8-9 parts of stove core soil, and 12-15 parts of sea clam shell.

[0009] The above-mentioned traditional Chinese medicine composition provided by the present invention has been demonstrated through clinical trials to have a good therapeutic effect on different grades of liver-stomach disharmony type reflux esophagitis, with a total effective rate of up to 95%; it also has a good repair effect on damaged esophageal mucosa, especially for grade A and B reflux esophagitis, with a total effective rate of 91.7%. Therefore, the traditional Chinese medicine composition can be used in the preparation of drugs for treating liver-stomach disharmony type reflux esophagitis.

[0010] The dosage form of the drug for treating hepato-gastric disharmony type reflux esophagitis of the present invention is an oral preparation, and the oral preparation is selected from any one of granules, tablets, capsules, powders, oral liquids or pills.

[0011] The present invention also provides a traditional Chinese medicine granule for treating reflux esophagitis of liver-stomach disharmony type, which comprises the following raw materials by weight: 6-12 grams of green peel, 6-12 grams of dried tangerine peel, 6-12 grams of peony bark, 5-10 grams of magnolia bark, 6-12 grams of qinpi, 5-10 grams of calcined walnut seeds, 5-10 grams of cuttlefish bone, 3-9 grams of ginger, 5-10 grams of sandalwood, 8-15 grams of salvia miltiorrhiza, 8-15 grams of calcined oyster shell, 5-10 grams of immature bitter orange, 5-9 grams of stove core soil, and 8-15 grams of sea clam shell; The preparation method of the Chinese medicine granules comprises the following steps: Step 1. Process the green peel and the tangerine peel together, grind them into coarse powder, sieve them, mix the coarse powder with enzyme solution for enzymolysis, then add water for decoction, filter and extract the juice, dry, grind and sieve them to obtain dry extract powder for later use; Step 2. Slice the cortex qinpi and the cortex moutan, soak them, extract them at 80°C, filter them while keeping them warm, concentrate them under reduced pressure, freeze them to form a brittle solid, and grind them with air flow to obtain a dry extract powder for later use; Step 3. Crush the Magnolia officinalis to a coarse powder and sieve; crush the Citrus aurantium immaturus shell; mix the two, add 50% ethanol, and perform ultrasonic-microwave synergistic extraction at room temperature; slice the Salvia miltiorrhiza, add 50% ethanol, and perform ultrasonic-microwave synergistic extraction at 60°C. After cooling, filter the extract, combine it with the Magnolia officinalis and Citrus aurantium immaturus extracts, and concentrate under reduced pressure to obtain an extract. After that, add microcrystalline cellulose, spray dry, and obtain a powder for later use; Step 4. Calcined corrugated paper is quenched with 20% rice vinegar, air-dried, air-pulverized, and ball-milled to 300-500 nm. Calcined oysters are quenched with 20% rice vinegar until crisp, air-dried, air-pulverized, separated by a classifier, and passed through a 325-mesh sieve for later use. Cuttlefish bones are boiled in a 2% NaOH solution at 80°C for 1 hour, washed with water until neutral, soaked in 5% acetic acid for 1 hour, washed with water to a pH of 6.5-7.0, air-dried, and air-pulverized to a D50 of 5 μm. Sea clam shells are softened and calcined at 150°C, added to 20% rice vinegar, stirred until free of bubbles, filtered, passed through a 200-mesh sieve, added to a PVP-K30 aqueous solution, stirred in a 60°C water bath, vacuum-filtered, and ball-milled to a D90 of ≤400 nm. Hearth soil is boiled in 10% hydrochloric acid, washed with water to a pH of 6.0, calcined at 750°C for 4 hours, and air-pulverized to a D90 of ≤2 μm. The above five ultrafine powders are mixed and set aside. Step 5. Slice ginger, extract with supercritical CO2, and collect ginger volatile oil; crush sandalwood to obtain coarse powder, sieve, extract with supercritical CO2, and collect sandalwood volatile oil; combine ginger volatile oil and sandalwood volatile oil, then include them in a ratio of oil:β-cyclodextrin = 1:6, stir, and spray dry to obtain inclusion compound powder; Step 6. Mix the powders obtained in step 1, step 2, step 3 and step 5, spray with 8% ethanol to moisten, add the mixed powder obtained in step 4, add starch and dextrin, mix well, roll and form granules by dry method.

[0012] As a preferred embodiment of the present invention, the enzyme in the enzyme solution in step 1 is cellulase.

[0013] As a preferred embodiment of the present invention, in step 3, 15% of the amount of microcrystalline cellulose extract is added and spray-dried at 135°C.

[0014] As a preferred embodiment of the present invention, in step 5, the ginger is sliced ​​and then subjected to supercritical CO2 extraction at 35°C and 20MPa; the sandalwood is crushed into coarse powder and passed through a 20-mesh sieve, and then subjected to supercritical CO2 extraction at 40°C and 25MPa.

[0015] As a preferred embodiment of the present invention, in step 6, 40% of the main drug amount of starch and dextrin is added at a ratio of 1:1.

[0016] In the traditional Chinese medicine composition provided by the present invention, the peel of green tea is bitter, pungent, and warming; it enters the liver, gallbladder, and stomach meridians, soothes the liver, breaks up qi, and eliminates stagnation. Liver-stomach disharmony is centered around liver depression and qi stagnation. Green tea peel has a pungent, dispersing, and bitter, purging properties, specifically entering the liver meridian, effectively breaking up qi stagnation caused by liver depression, unblocking qi flow, and relieving chest and flank pain, as well as epigastric distension and fullness. Its entry into the stomach meridian can eliminate stagnation, aid in the descent of stomach qi, and is effective for treating epigastric distension and frequent belching caused by qi stagnation in reflux esophagitis. Furthermore, green tea peel contains limonene volatile oil, flavonoids (hesperidin), and alkaloids. The volatile oil can promote gastrointestinal motility, relax smooth muscle, and relieve spasms; the flavonoids have anti-inflammatory and gastrointestinal motility-regulating effects.

[0017] Tangerine peel: Pungent, bitter, and warm; it enters the spleen and lung meridians; it regulates qi and strengthens the spleen, dries dampness and resolves phlegm. Used in conjunction with tangerine peel, tangerine peel is particularly effective in regulating spleen and stomach qi, drying dampness and resolving phlegm, and relieving epigastric fullness, nausea, and acid reflux caused by spleen deficiency and dampness. Its warm, yet not dry, nature helps regulate qi flow while soothing the stomach and relieving reflux symptoms of reflux esophagitis, characterized by stagnation of spleen and stomach qi and phlegm-dampness. Tangerine peel's main components include hesperidin, hesperidin, limonene, and vitamin C. Hesperidin protects the gastric mucosa and inhibits excessive gastric acid secretion; its volatile oils promote digestive juice secretion, enhance gastrointestinal motility, and regulate gastrointestinal function.

[0018] Peony bark: bitter, pungent, slightly cold; enters the heart, liver, and kidney meridians; clears heat and cools blood, promotes blood circulation and removes blood stasis, and reduces deficiency fever; long-term liver-stomach disharmony can easily turn into heat, burn the stomach meridians, and cause heartburn, burning pain in the stomach and other heat symptoms; Peony bark is bitter and cold and clears heat, clears stagnant heat in the blood, and relieves acid reflux and heartburn caused by stomach heat; its blood circulation and blood stasis function can improve esophageal mucosal congestion and edema, and promote damage repair; Peony bark contains paeonol, paeonol, paeoniflorin, etc.; paeonol has anti-inflammatory, analgesic, and anti-ulcer effects, can inhibit gastric acid secretion, and reduce gastric mucosal inflammation; the blood circulation and blood stasis-removing ingredients can improve local blood circulation and promote tissue repair.

[0019] Magnolia officinalis: bitter, pungent, and warm; enters the spleen, stomach, lung, and large intestine meridians; dries dampness and eliminates phlegm, and relieves gas and fullness; for those with liver-stomach disharmony and dampness and turbidity blocking the middle part of the body, Magnolia officinalis is bitter and warm, dries dampness, and pungent and warm to promote qi circulation. It can not only transform dampness and turbidity in the spleen and stomach, but also promote the downward movement of gastrointestinal qi, relieve symptoms such as abdominal distension, nausea, vomiting, and constipation; its ability to relieve gastric qi and fullness can help stomach qi descend and reduce gastric acid reflux; Magnolia officinalis contains magnolol, honokiol, volatile oil, etc.; magnolol has anti-ulcer, anti-inflammatory, and antibacterial effects, can inhibit Helicobacter pylori, regulate gastrointestinal smooth muscle tension, promote gastrointestinal emptying, and reduce reflux.

[0020] Qinpi: bitter, astringent, and cold; enters the liver, gallbladder, and large intestine meridians; clears heat and dries dampness, astringes and stops dysentery, and improves eyesight; in reflux esophagitis, Qinpi is bitter, cold, and heat-clearing, and is good at clearing damp heat from the liver, gallbladder, and large intestine, and is effective in treating bitter taste in the mouth, acid reflux, and burning pain in the stomach caused by liver and stomach heat; its astringency can astringe the mucosa and relieve the burning sensation after esophageal mucosal damage, similar to the effect of "clearing heat and healing sores"; Qinpi contains coumarin ingredients such as aesculin, aesculetin, esculin, esculetin, and other coumarin ingredients; these ingredients have anti-inflammatory, antibacterial, and antioxidant effects, can reduce esophageal mucosal inflammation, and promote ulcer healing.

[0021] Calcined cornstarch: salty, neutral; enters the lung, stomach, and liver meridians; eliminates phlegm, softens hard masses, reduces acidity and relieves pain; calcined cornstarch is salty and cold and enters the stomach, is good at controlling stomach acid, and is a commonly used medicine for treating acid reflux and heartburn; its texture is hard and can neutralize stomach acid after calcination, relieve the irritation of stomach acid on the esophageal mucosa, and enter the liver meridian at the same time, and can also soothe the liver and regulate qi, and is suitable for those with liver-stomach disharmony and excessive stomach acid; the main components of calcined cornstarch are calcium carbonate, trace elements iron, zinc, etc.; calcium carbonate can neutralize stomach acid, increase the pH value in the stomach, and relieve reflux symptoms; the trace elements it contains may be involved in mucosal repair.

[0022] Cuttlefish bone: salty, astringent, and warm; enters the spleen, stomach, and kidney meridians; astringent and hemostatic, astringent and leukorrhea-stopping, antacid and analgesic, and can heal sores and regenerate tissue; cuttlefish bone has significant antacid and analgesic effects, which can not only neutralize stomach acid, but also astringent and protect the esophagus and gastric mucosa, and promote ulcer healing; its astringent taste can astringe dissipated qi, and combined with liver-soothing and qi-regulating drugs, it can enhance the effect of harmonizing the stomach and relieving reverse flow, and is suitable for those with acid reflux, epigastric pain, and mucosal damage; the main components of cuttlefish bone are calcium carbonate, chitin, amino acids, etc.; calcium carbonate neutralizes stomach acid, chitin can form a protective film on the mucosal surface, and amino acids promote tissue repair. At the same time, the gelatin components it contains can protect the esophageal mucosa.

[0023] Ginger: pungent, warm; enters the lung, spleen, and stomach meridians; relieves exterior symptoms and dispels cold, warms the middle and stops vomiting, resolves phlegm and relieves cough; ginger is known as the "holy medicine for vomiting", warms the stomach and dispels cold, harmonizes the middle and reduces adverse reactions, and is effective for nausea, vomiting, and watery stomach caused by stomach cold in liver-stomach disharmony; its pungent and warm nature can restrain the cooling effects of bitter and cold medicines, harmonize various medicines, and enhance the spleen and stomach's transportation and transformation functions; ginger contains gingerol, gingerol, shogaol, gingerol volatile oil, zingiberene, etc.; gingerol can promote gastrointestinal motility, inhibit excessive gastric acid secretion, and relieve nausea and vomiting; volatile oil has anti-inflammatory and analgesic effects, and improves gastric mucosal blood circulation.

[0024] Sandalwood: pungent, warm; enters the spleen, stomach, and lung meridians; promotes qi circulation and warms the middle, stimulates appetite and relieves pain; sandalwood is pungent, warm, and fragrant, and is good at regulating spleen and stomach qi stagnation, warming the middle and promoting qi circulation, relieving cold pain, bloating, and discomfort in the epigastric region, and is especially suitable for those with liver and stomach disharmony and cold stomach; it promotes qi circulation without consuming qi, warms the body without being dry and intense, and can enhance the qi-regulating function of tangerine peel and green peel, while also stimulating appetite and relieving pain; sandalwood contains volatile oil components such as santalol, santalene, and sandalwood oil; santalol can regulate gastrointestinal nerve function, relieve smooth muscle spasms, and alleviate epigastric pain; volatile oils can promote the secretion of digestive juices and enhance gastrointestinal motility.

[0025] Danshen: bitter, slightly cold; enters the heart and liver meridians; promotes blood circulation and removes blood stasis, regulates menstruation and relieves pain, clears the heart and relieves restlessness, cools blood and eliminates carbuncle; long-term reflux esophagitis can easily lead to qi and blood stasis, congestion, edema and even erosion of the esophageal mucosa, Danshen promotes blood circulation and removes blood stasis, improves local blood circulation in the esophagus, and promotes mucosal repair; its slightly cold nature can clear away stagnant heat in the blood, and when combined with peony bark, it enhances the effects of clearing heat, cooling blood, dispersing blood stasis and relieving pain; Danshen contains tanshinone IIA, danshensu, and salvianolic acid B; tanshinone IIA can be anti-inflammatory, anti-ulcer, and improve microcirculation; salvianolic acid B has antioxidant effects, protects the gastric mucosa, and promotes the repair of damaged tissues.

[0026] Calcined oyster: salty, slightly cold; enters the liver and kidney meridians; suppresses yang and replenishes yin, calms the mind, softens and disperses lumps, astringes and solidifies, antagonizes acid and relieves pain; calcined oyster is salty, cold and heavy in nature, has strong antacid and analgesic power, can neutralize stomach acid, relieve heartburn and acid reflux; its astringent and solidifying function can protect the esophageal mucosa, reduce the irritation of gastric acid reflux on the mucosa, and is suitable for those with excessive gastric acid and mucosal damage; in addition, its sedative nature can reduce the upward stomach qi and help the qi to move downward; the main components of calcined oyster are calcium carbonate, calcium phosphate, amino acids, etc.; calcium carbonate neutralizes stomach acid, amino acids promote mucosal repair, and the trace elements it contains (such as zinc and copper) participate in enzyme synthesis, enhancing tissue repair ability.

[0027] Citrus aurantium: bitter, pungent, sour, slightly cold; enters the spleen and stomach meridians; breaks up qi and eliminates stagnation, resolves phlegm and relieves abdominal distension; Citrus aurantium is pungent and dispersing, and bitter and laxative, with strong power to break up qi and eliminate stagnation, can clear and descend gastrointestinal qi, promote gastrointestinal motility, eliminate abdominal distension, accelerate gastric emptying, and reduce gastric acid reflux; when used with Citrus aurantium and Citrus reticulata, it enhances the function of soothing the liver and regulating qi, harmonizing the stomach and relieving adverse reactions, and is targeted at fullness, belching, and reflux caused by liver-stomach disharmony; Citrus aurantium contains volatile oils (such as limonene), flavonoids (such as hesperidin), synephrine, etc.; synephrine can excite α receptors, enhance gastrointestinal smooth muscle contractility, and promote gastric emptying; flavonoids regulate gastrointestinal motility, have anti-inflammatory effects, and protect the gastric mucosa.

[0028] Stove Heart Earth: pungent, warm; enters the spleen and stomach meridians; warms the middle to stop bleeding, vomiting, and diarrhea; Stove Heart Earth is pungent and warm and enters the spleen and stomach, good at warming the middle and harmonizing the stomach, relieving nausea and vomiting, and is effective for those with liver-stomach disharmony and spleen and stomach deficiency and coldness, relieving symptoms such as vomiting of clear water, dull pain in the stomach, and loose stools; its adsorption effect can reduce the irritation of gastric acid on the mucosa, and at the same time astringe and stop bleeding, and is suitable for those with reflux esophagitis combined with mucosal bleeding; Stove Heart Earth is mainly composed of minerals such as silicate, calcium, iron, aluminum, and organic matter; minerals can neutralize gastric acid and adsorb harmful substances in the stomach, and organic matter has the function of protecting gastric mucosa and promoting ulcer healing.

[0029] Sea clam shell: salty, cold; enters the lung and stomach meridians; clears heat and resolves phlegm, softens and disperses lumps, and reduces acidity and relieves pain; the salty and cold nature of sea clam shell enters the stomach, which can not only clear stomach heat and resolve hot phlegm, but also treat heartburn, bitter taste in the mouth, and sticky phlegm caused by liver and stomach heat; it can also reduce acidity and relieve pain, neutralize stomach acid, and relieve acid reflux symptoms; its softening and dispersing lumps function can improve tissue hyperplasia or adhesions after inflammation of the esophageal mucosa, and is suitable for reflux esophagitis with obvious heat signs; the main components of sea clam shell are calcium carbonate, chitin, amino acids, etc.; calcium carbonate neutralizes stomach acid, chitin protects the mucosa, and its cold components can suppress stomach heat and relieve burning sensation.

[0030] This prescription uses Citrus aurantium, Citrus aurantium immaturum, calcined Corrugated Bark Fruit, and Cuttlefish Bone as the main ingredients; Citrus aurantium is powerful and specifically enters the liver and gallbladder, breaking up Qi and soothing the liver, eliminating accumulation and relieving pain, and strongly breaks up and disperses Qi stagnation in the liver meridian, relieving distension and pain in the ribs; Citrus aurantium is strong and enters the spleen and stomach meridians, breaking up Qi and eliminating accumulation, resolving phlegm and dispersing abdominal distension, descending Qi and eliminating fullness, and guiding stomach Qi downward; calcined Corrugated Bark Fruit and Cuttlefish Bone antacid and relieve pain, neutralize stomach acid, and protect the mucosa. The two are often used together to enhance the antacid effect, directly attacking the core pathogenesis of liver Qi stagnation, horizontal reversal invading the stomach, stomach disharmony and descending, and Qi reversal and acid attacking the esophagus. The auxiliary herb, tangerine peel, regulates qi and strengthens the spleen, dries dampness and resolves phlegm, regulates qi stagnation in the spleen and stomach, promotes transportation and transformation, and prevents qi stagnation from generating phlegm and dampness. Magnolia bark dries dampness and eliminates phlegm, relieves qi distension, and calms upward qi. Calcined oyster shells also suppress yang, while sea clam shells are cold and clear heat, enhancing their antacid and analgesic effects. Sandalwood promotes qi and relieves pain, dispels cold and regulates the middle, and relieves diaphragm and chest tightness. Paeony bark clears heat and cools blood, promoting blood circulation and removing blood stasis, while qinpi clears heat and dries dampness, assisting the main herb in clearing both heat and blood stasis, preventing heat-induced damage to yin and blood circulation. Salvia miltiorrhiza is added as an adjuvant to promote blood circulation and remove blood stasis, dredge menstruation, relieve pain, and cool blood to relieve restlessness. Stove heart soil and ginger work together to warm the middle, arrest bleeding, and relieve nausea, counteracting the cold properties of qinpi, paeony bark, salvia miltiorrhiza, and sea clam shells, preventing excessive stomach damage. They also have a astringent effect, protecting the mucosa. Ginger, with its warming and stomach-regulating properties, directs the medicinal effects to the middle jiao spleen and stomach, acting as a guiding agent. The whole prescription regulates the Qi mechanism by soothing the liver and relieving depression, regulating Qi and harmonizing the stomach, reducing adverse reactions and reducing acidity to treat the symptoms of reflux, and assisting with clearing away heat and removing blood stasis to eliminate the changes of stagnant heat and blood stasis. At the same time, it takes into account warming the middle and harmonizing the stomach, and protecting the mucosa. The prescription is rigorous, well-structured, and highly targeted, reflecting the TCM philosophy of "differential diagnosis and treatment" and "treating both the symptoms and the root cause."

[0031] Advantages and beneficial effects of the present invention: (1) The Chinese medicine composition provided by the present invention contains qinpi and moutan bark that clear away heat without causing excessive cold, and the combination of stove heart soil and ginger can improve the dull pain in the stomach and loose stools caused by long-term use of bitter and cold medicines. The combined use of calcined corrugated seeds, cuttlefish bone, calcined oyster shell, and sea clam shell has a calcium carbonate content of over 60%, and its gastric acid neutralization efficiency is 2-3 times that of a single drug. The amino acid components of cuttlefish bone and calcined oyster shell can promote the secretion of epidermal growth factor and accelerate mucosal healing, making it more suitable for long-term use. Based on many years of clinical experience, it has been proven that the Chinese medicine composition can achieve good therapeutic effects when used alone, and has the advantages of rapid onset, stable efficacy, and high total efficacy in the treatment of reflux esophagitis caused by liver-stomach disharmony.

[0032] (2) The Chinese medicine granules provided by the present invention have the advantages of pure combination, safety and effectiveness, advanced technology, easy to take and carry, and high bioavailability, and are extremely competitive in the market. Ultrafine grinding technology is adopted in the preparation of granules, and the volatile oil retention rate reaches 98%. Ultrasonic-microwave synergistic extraction achieves a cell wall rupture rate of 95%. β-cyclodextrin inclusion and microcapsule sustained release increase the solubility of insoluble components by 12 times and the bioavailability by 2.5 times, significantly enhancing the therapeutic effect.

[0033] (3) The Chinese medicine composition provided by the present invention regulates the fundamental function of Qi by relieving liver depression, regulating Qi and harmonizing the stomach, treating the symptoms of reflux by reducing adverse reactions and reducing acidity, and assisting with clearing away heat and removing blood stasis to eliminate the changes of stagnant heat and blood stasis. At the same time, it takes into account warming the middle and harmonizing the stomach, and protecting the mucosa. The prescription is rigorous, well-organized, and highly targeted, reflecting the Chinese medicine idea of ​​"differentiation of symptoms and treatment" and "treating both the symptoms and the root cause". The prescription does not need to be used in conjunction with Western medicine. It has a good therapeutic effect on different grades of liver-stomach disharmony type reflux esophagitis, with a total effective rate of up to 95%.

[0034] (4) The Chinese medicine composition provided by the present invention has a good repair effect on damaged esophageal mucosa, especially for patients with grade A and B reflux esophagitis, with a total effective rate of 91.7%. It also has a good therapeutic effect on patients with grade C and D reflux esophagitis, with a total effective rate of 85%. The good repair effect can restore the normal barrier function of the esophageal mucosa, effectively block the erosion of reflux substances such as gastric acid and pepsin, reduce the possibility of the esophagus being damaged again, and thus reduce the recurrence rate of reflux esophagitis. DETAILED DESCRIPTION

[0035] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below. The description herein is only used to explain the present invention and is not intended to limit the present invention.

[0036] The present invention discloses a traditional Chinese medicine composition, a traditional Chinese medicine granule, and a preparation method for treating reflux esophagitis caused by liver-stomach disharmony. Those skilled in the art may refer to the present disclosure and appropriately modify the component parameters or process parameters to achieve the desired effect. It should be noted that all similar substitutions and modifications obvious to those skilled in the art are considered to be within the scope of protection of the present invention.

[0037] Example 1:

[0038] This embodiment provides a traditional Chinese medicine composition for treating reflux esophagitis of liver-stomach disharmony type, which is composed of the following raw materials by weight: 12 parts of green peel, 10 parts of dried tangerine peel, 10 parts of peony bark, 8 parts of magnolia bark, 12 parts of qinpi, 8 parts of calcined corrugated fruit, 10 parts of cuttlefish bone, 8 parts of ginger, 9 parts of sandalwood, 10 parts of salvia miltiorrhiza, 12 parts of calcined oyster shell, 6 parts of immature bitter orange, 8 parts of stove core soil, and 12 parts of sea clam shell.

[0039] Example 2:

[0040] The present embodiment provides a traditional Chinese medicine granule for treating reflux esophagitis of liver-stomach disharmony type, comprising the following raw materials by weight: 12 parts of green peel, 10 parts of dried tangerine peel, 10 parts of peony bark, 8 parts of magnolia bark, 12 parts of qinpi, 8 parts of calcined walnut seeds, 10 parts of cuttlefish bone, 8 parts of ginger, 9 parts of sandalwood, 10 parts of salvia miltiorrhiza, 12 parts of calcined oyster shell, 6 parts of immature bitter orange, 8 parts of stove core soil, and 12 parts of sea clam shell; The preparation method of the Chinese medicine granules comprises the following steps: Step 1. Green peel and tangerine peel are co-processed, mixed and ground into coarse powder, and passed through a 10-mesh sieve. The coarse powder is mixed with enzyme solution at a material-liquid ratio of 1:10 (g / mL). The pH of the system is adjusted to 4.5 with 1 mol / L hydrochloric acid. The mixture is placed in a constant temperature water bath and enzymatically hydrolyzed at 50°C with magnetic stirring (200 rpm) for 1 hour. Then, 10 times the amount of water is added and boiled, and the mixture is gently boiled for 1 hour. The juice is filtered to obtain the juice, dried in a vacuum belt dryer at -0.09 MPa and 60°C, and then ground and passed through an 80-mesh sieve to obtain a dry extract powder for later use. Specifically, the enzyme solution is prepared by adding 0.5 g of cellulase to 1000 mL of water. In this embodiment, the precise catalysis of the biological enzymes first achieves gentle cell wall breaking, increasing the extraction rate by 30%-40% and retaining more volatile active ingredients.

[0041] Step 2. Cut the cortex fraxini and the cortex moutan into 1 mm slices; soak them in cold water for 2 hours; combine the two and extract them twice at 80°C for 1.5 hours each time; keep warm and filter to prevent the solubility of components such as aesculin from decreasing due to the temperature dropping below 60°C and precipitation; concentrate under reduced pressure at 65°C to a relative density of 1.25-1.30 to obtain an extract, freeze it in a -20°C refrigerator for 4 hours to form a brittle solid, and grind it in a low-temperature airflow at -20°C with a D90 of ≤45 μm to obtain a dry extract powder for later use; Step 3. Crush the Magnolia officinalis to coarse powder and pass it through a 30-mesh sieve; crush the Citrus aurantium immaturus shell; after mixing the two, add 50% ethanol at a solid-liquid ratio of 1:8, set the microwave ultrasonic synergistic extraction instrument to 400W microwave + 40kHz, and perform ultrasonic-microwave synergistic extraction at room temperature for 30 minutes; cut Salvia miltiorrhiza into 2mm slices, add 50% ethanol, and perform ultrasonic-microwave synergistic extraction at 60°C for 30 minutes (400W microwave + 40kHz). After cooling, fine filtration is performed, and the extract is combined with the Magnolia officinalis and Citrus aurantium immaturus extracts, and concentrated under reduced pressure at 40°C to a relative density of 1.25-1.30. Microcrystalline cellulose is added at 15% of the extract volume, and the extract is spray-dried at 135°C to obtain a powder for later use; Step 4. The calcined corrugated paper was quenched three times with 20% rice vinegar (analytical grade) at a liquid-to-solid ratio of 1:1 (g / mL) to release trace elements such as magnesium, iron, and zinc from the mineral lattice, thereby increasing bioavailability by approximately 1.5 times. The paper was stirred for 30 minutes each time until no bubbles were present and the pH was adjusted to 8.0, which is close to the human body fluid environment, reducing irritation while retaining the ability to neutralize gastric acid. The paper was then air-dried at 105°C for 1 hour, with the moisture content controlled to ≤1.5%. The quenched fragments were then air-milled to a D90 of ≤10 μm and high-energy ball milled to a particle size of 300-500 nm to obtain a powder. Calcined oyster shells were quenched with 20% rice vinegar at a liquid-to-solid ratio of 1:1.5 (g / mL) until crispy, stirred for 30 minutes until no bubbles appeared and the pH dropped to 8.0-8.5, dried at 105°C for 1 hour, pulverized by three cycles of airflow at 0.5 MPa, separated by a classifying wheel at 2800 rpm, and passed through a 325-mesh sieve for later use. Cuttlefish bones were boiled in 2% NaOH solution at 80°C for 1 hour, with an organic matter removal rate of 92% and a calcium carbonate retention rate of ≥90% at a pH of 12.0-12.5. They were then washed with water until neutral, soaked in 5% acetic acid for 1 hour (pH 4.0-4.5), washed with water until pH 6.5-7.0, dried at 105°C for 2 hours, and pulverized with supersonic airflow at -40°C to a D50 of 5 μm. The sea clam shells were softened and calcined at 150°C for 30 minutes to retain more than 95% of the calcium carbonate. 20% rice vinegar (analytical grade) was added at a ratio of 1:1 (g / mL) and stirred until there were no bubbles (approximately 30 minutes). The pH was controlled at 9.0-9.5. After filtration, the shells were passed through a 200-mesh sieve. A 10% aqueous solution of PVP-K30 (polyvinyl pyrrolidone) was slowly added at a ratio of 2% (calculated as precipitated calcium carbonate). The shells were stirred in a 60°C water bath for 2 hours, vacuum filtered, and ground in a ball mill for 3 hours at a speed of 600 r / min. The particle size was tested to be D90 ≤ 400 nm, and the powder was collected. Stove core soil, boiled in 10% hydrochloric acid for 30 minutes, washed with water to pH 6.0, calcined at 750℃ for 4 hours, air flow crushed to D90 ≤ 2μm, and the above five kinds of ultrafine powders were mixed and set aside; Step 5. Slice ginger and extract it with supercritical CO2 at 35°C and 20 MPa to collect ginger volatile oil. The content of gingerol components, which mainly play an anti-cold and anti-emetic role, in the ginger volatile oil is relatively stable. Sandalwood is crushed into coarse powder and passed through a 20-mesh sieve. Supercritical CO2 extraction is performed at 40°C and 25 MPa to collect sandalwood volatile oil. α-santalol accounts for 60%-70% of the sandalwood volatile oil, which has a central nervous system inhibitory and sedative effect. The ginger volatile oil and the sandalwood volatile oil are combined and then included in a mixture of oil:β-cyclodextrin at a ratio of 1:6, stirred at 40°C for 2 hours, and spray-dried to obtain an inclusion complex powder. Step 6. The dried extract powder of green peel and tangerine peel in step 1, the dried extract powder of peony bark and qinpi in step 2, the magnolia bark, immature bitter orange, and salvia miltiorrhiza powder in step 3, and the ginger and sandalwood inclusion compound powder in step 5 are mixed by a three-dimensional mixer, sprayed with 8% ethanol to moisten, and the calcined corrugated paper, cuttlefish bone, calcined oyster, stove core soil, and sea clam shell ultrafine powder in step 4 are added, and 40% of the main drug amount of starch and dextrin are added in a ratio of 1:1 (starch and dextrin are added in a ratio of 1:1), rolled at 8MPa, and granulated by a 16-mesh dry method.

[0042] Example 3:

[0043] The difference from Example 2 is that the Chinese medicine granules include the following raw materials by weight: 12 parts of green peel, 12 parts of dried tangerine peel, 8 parts of peony bark, 7 parts of Magnolia officinalis, 10 parts of Qinpi, 10 parts of calcined corrugated paper, 10 parts of cuttlefish bone, 9 parts of ginger, 10 parts of sandalwood, 15 parts of Salvia miltiorrhiza, 15 parts of calcined oyster, 10 parts of Citrus aurantium, 9 parts of stove core soil, and 15 parts of sea clam shell.

[0044] Example 4:

[0045] The difference from Example 2 is that the Chinese medicine granules include the following raw materials by weight: 6 parts of green peel, 6 parts of dried tangerine peel, 6 parts of peony bark, 5 parts of Magnolia officinalis, 6 parts of Qinpi, 5 parts of calcined corrugated paper, 5 parts of cuttlefish bone, 3 parts of ginger, 5 parts of sandalwood, 8 parts of Salvia miltiorrhiza, 8 parts of calcined oyster, 5 parts of Citrus aurantium, 5 parts of stove core soil, and 8 parts of sea clam shell.

[0046] Example 5:

[0047] The difference from Example 2 is that the Chinese medicine granules include the following raw materials by weight: 12 parts of green peel, 6 parts of dried tangerine peel, 10 parts of peony bark, 6 parts of Magnolia officinalis, 8 parts of Qinpi, 6 parts of calcined corrugated fruit, 8 parts of cuttlefish bone, 5 parts of ginger, 6 parts of sandalwood, 10 parts of Salvia miltiorrhiza, 10 parts of calcined oyster, 6 parts of Citrus aurantium, 7 parts of stove core soil, and 10 parts of sea clam shell.

[0048] Comparative Example 1: The difference from Example 2 is that the preparation method of the Chinese medicine granules is different, as follows: Step 1. Remove impurities from green peel, dried tangerine peel, peony bark, Magnolia officinalis, Fraxinus chinensis, immature bitter orange, and salvia miltiorrhiza, wash them, dry them at 60°C, grind them into coarse powder and pass through a 20-mesh sieve, mix them, add 10 times the amount of water and decoct them twice, each time for 30 minutes, filter, combine the filtrates, concentrate them to a relative density of 1.10-1.20, add ethanol to make the alcohol content reach 60%, let it stand for 24 hours, filter, recover ethanol, concentrate them into a thick paste with a relative density of 1.30-1.35, dry them in an oven at 70°C, grind them into extract powder and pass through an 80-mesh sieve for later use; Step 2. Wash ginger and cut into 2-3 mm thick slices. Crush sandalwood into coarse powder and pass through a 20-mesh sieve. Mix the two according to the prescribed amount, add 10 times the amount of water, soak for 30 minutes, connect to a volatile oil extractor, heat and distill for 6-8 hours, collect the volatile oil, dehydrate with anhydrous sodium sulfate, dissolve the volatile oil in ethanol, slowly add dropwise to 8 times the amount of saturated β-CD aqueous solution, stir at 50°C for 2 hours, refrigerate for 24 hours, filter, dry, and grind through an 80-mesh sieve to prepare inclusion compound powder for later use; Step 3. Calcine the corrugated shells, oyster shells, and clam shells at 200°C for 30 minutes until they are red hot. Immediately place them in 40% rice vinegar (50% by weight of the herbs) to quench them. Remove and dry them, then grind them through a 100-mesh sieve and set aside. Wash and dry the cuttlefish bones, then grind them directly through a 100-mesh sieve to retain the activity of calcium carbonate and set aside. Sieve the stove core soil through a 100-mesh sieve to remove sand and gravel impurities, then fry it in a pot over low heat until it is slightly charred to enhance its adsorption capacity. Set aside. Step 4. Mix the extract powder of the green peel and other ingredients in step 1 with the ginger and sandalwood inclusion compound powder in step 2, spray 15% of the total amount of the main drug with 8% concentration ethanol to moisten it, and at the same time add calcined corrugated paper, cuttlefish bone, sea clam shell, calcined oyster, and stove core soil powder, add 50% of the weight of the main drug in a ratio of 1:1 starch and dextrin (starch and dextrin are added in a ratio of 1:1), mix until the material is uniform and loose, and dry granulate to obtain the product.

[0049] The method of using the Chinese medicine granules for treating reflux esophagitis of liver-stomach disharmony type of this embodiment is: 1 bag each time (1 bag is 10g), 2 times / day, 7 days as a course of treatment, and 1 to 6 courses of treatment are used.

[0050] It should be noted that the Chinese medicine composition provided in this embodiment can be appropriately added or subtracted according to the severity of the patient's symptoms and the length of the course of the disease during clinical use. For example, for patients with severe liver and stomach heat, the amount of peony bark and qinpi can be increased to 12 parts, and the amount of sea clam shell can be increased to 15 parts; for patients with mild spleen and stomach cold, the amount of ginger can be reduced to 3 parts; for patients with qi stagnation and blood stasis, the amount of salvia miltiorrhiza can be increased to 15 parts, and the amount of santalin can be increased to 10 parts; of course, the amount of each raw material of the above-mentioned Chinese medicine composition needs to be controlled within the following range no matter how it is added or subtracted: Green peel 6-12, dried tangerine peel 6-12, peony bark 6-12, Magnolia officinalis 5-10, Qinpi 6-12, calcined cortex 5-10, cuttlefish bone 5-10, ginger 3-9, sandalwood 5-10, salvia miltiorrhiza 8-15, calcined oyster 8-15, Citrus aurantium 5-10, stove core soil 5-9, sea clam shell 8-15.

[0051] The Chinese medicine composition provided in this embodiment uses Citrus aurantium, Citrus aurantium immaturus, calcined Corrugated Fructus, and Cuttlefish Bone as the main ingredients; Citrus aurantium, Magnolia officinalis, calcined Oyster Shell, Sea Clam Shell, Santalum album, Paeonia suffruticosa, and Fraxinus chinensis as the secondary ingredients; Salvia miltiorrhiza, Stovetopelta, and Zingiber officinale as the adjuvant ingredients; Ginger, because it warms the middle and harmonizes the stomach, directs the medicinal power to the middle jiao spleen and stomach, and has the effect of guiding the medicine to the meridians. The entire formula works by soothing the liver and relieving depression, regulating qi and harmonizing the stomach to regulate the fundamental qi mechanism, lowering adverse qi and suppressing acid to treat reflux symptoms, and supplemented by clearing heat and removing blood stasis to eliminate the changes caused by stagnant heat and blood stasis, while also taking into account warming the middle and harmonizing the stomach and protecting the mucosa. The formula is rigorous, well-organized, and highly targeted, embodying the TCM philosophy of "differentiation of symptoms and treatment" and "treating both the symptoms and the root cause." This recipe has been used for many years at the Third Clinical Affiliated Hospital of Changchun University of Chinese Medicine and Ying's TCM Clinic, and has shown good therapeutic effects for patients with reflux esophagitis characterized by liver-stomach disharmony. The therapeutic effect of the Chinese medicine composition of the present invention is illustrated below by clinical data. The Chinese medicine granules prepared in Example 2 and Example 3 are used to treat patients with liver-stomach disharmony type reflux esophagitis, and they are respectively recorded as Example 2 Chinese medicine granules and Example 3 Chinese medicine granules. The specific situation is as follows: 1. Case selection: As a traditional Chinese medicine granule for the treatment of reflux esophagitis, 320 patients with confirmed liver-stomach disharmony type reflux esophagitis were selected, aged 20-70 years, regardless of gender, with clinical symptoms of acid reflux, heartburn, and chest pain. According to the "Consensus on the Diagnosis and Treatment of Gastroesophageal Reflux Disease in Traditional Chinese Medicine (2017)": The main symptoms of liver-stomach disharmony type are "heartburn or reflux, epigastric distension and pain, frequent belching, and aggravated by emotional distress. The traditional Chinese medicine syndrome differentiation is liver-stomach disharmony type; it meets the diagnosis of reflux esophagitis in Western medicine and is accompanied by esophageal mucosal damage (determined by electronic gastroscopy results). According to the Los Angeles classification system of RE (reflux esophagitis), RE can be divided into four grades: A, B, C, and D. The grading standards are as follows: Grade A refers to one or more esophageal mucosal damage, with a damaged length of ≤5 mm; Grade B refers to one or more esophageal mucosal damage, with a damaged length of >5 mm. Grade C refers to at least two esophageal mucosal ruptures with fusion covering <75% of the esophageal circumference; and Grade D refers to mucosal ruptures with fusion covering ≥75% of the esophageal circumference, with a duration of ≥3 months and no use of acid suppressants, gastric mucosal protective agents, or other medications that could affect efficacy in the past 2 weeks. Patients with concurrent severe organic diseases, pregnant or lactating women, allergies to ethanol or traditional Chinese medicine ingredients, and those with other syndromes identified by Traditional Chinese Medicine (TCM) were excluded. The patients were randomly divided into four groups, each with 80 patients, and clinical observation was performed.

[0052] 2. Treatment methods: Among the four groups of patients with reflux esophagitis, three groups were selected to use the Chinese medicine granules of Example 2, Example 3 and Comparative Example 1, respectively, 1 bag each time, 10 g / bag, 2 times / d, 7 days as a course of treatment, and 4 courses of treatment. The remaining control sample group used omeprazole enteric-coated capsules (Levik), produced by Yuekang Pharmaceutical Group Co., Ltd., with a specification of 20 mg / capsule, 2 capsules each time, 2 times / d, combined with Zuojin Pills, produced by Hubei Ruihua Pharmaceutical Co., Ltd., with a specification of 18 g / bottle / box, 3 g each time, 2 times / d, 7 days as a course of treatment, and 4 courses of treatment.

[0053] 3. Efficacy assessment: The evaluation of syndrome efficacy is recommended to be based on the "Guiding Principles for Clinical Research of New Chinese Medicines (Trial)" and calculated using the nimodipine method: efficacy index = [(pre-treatment score - post-treatment score) / pre-treatment score] × 100%, which is divided into 4 levels: clinical cure, marked effect, effective, and ineffective.

[0054] 1) Clinical recovery: major symptoms and signs disappear or almost disappear, with efficacy index ≥95%; 2) Markedly effective: major symptoms and signs were significantly improved, with efficacy index of 70% ≤ < 95%; 3) Effective: Major symptoms and signs improved significantly, with efficacy index of 30% ≤ < 70%; 4) Ineffective: There is no significant improvement in the main symptoms and signs, or they may even worsen, and the efficacy index is less than 30%.

[0055] 4. Treatment results Table 1: Treatment of reflux esophagitis patients using Chinese herbal granules and control sample (omeprazole) Total number of patients / cases Recovered / case Significantly effective / case Effective / Example Invalid / Example Efficiency Control sample (omeprazole combined with Zuojin Pills) 80 22 18 17 23 71.25% Example 2 Chinese medicine granules 80 32 25 19 4 95.00% Example 3 Chinese medicine granules 80 30 26 18 6 92.50% Comparative Example 1 Chinese medicine granules 80 26 21 20 13 83.75% The above results show that the efficacy of the Chinese medicine granules of the present invention is significantly higher than that of the control sample group; and the Chinese medicine granules of Example 2 and Example 3 of the present invention have better therapeutic effects on patients with liver-stomach disharmony type reflux esophagitis than the Chinese medicine granules of Comparative Example 1. The improvement of the granule preparation process improves the bioavailability of the drug, thereby achieving better therapeutic effects.

[0056] In addition, the present invention also separately investigated the repair effect of Chinese medicine granules on damaged esophageal mucosa, as shown in Table 2: Table 2: Endoscopic findings in patients with reflux esophagitis using the Chinese medicine granules of Example 2 and control samples

[0057] The above results show that the Chinese medicine granules provided by the present invention have a good repair effect on the damaged esophageal mucosa, especially for grade A and B reflux esophagitis. The control sample group: the number of cured + markedly effective + effective cases is 44, and the total effective rate = 44 / 60×100% = 73.3%; the treatment group (Chinese medicine granules of Example 2): the number of cured + markedly effective + effective cases is 55, and the total effective rate = 55 / 60×100% = 91.7%; It can be seen that the present invention has a higher total effective rate for patients with grade A and B reflux esophagitis and a significant effect; in addition, The present invention also has a good therapeutic effect on patients with grade C and D reflux esophagitis. In the control sample group, the number of cured + markedly effective + effective cases was 10, and the total effective rate was 10 / 20×100%=50%; in the treatment group, the number of cured + markedly effective + effective cases was 17, and the total effective rate was 17 / 20×100%=85%, which was significantly better than the control group. The good repair effect can restore the normal barrier function of the esophageal mucosa, effectively block the erosion of reflux substances such as gastric acid and pepsin, reduce the possibility of the esophagus being damaged again, and thus reduce the recurrence rate of reflux esophagitis.

[0058] The Chinese medicine granules provided by the present invention determine the course of treatment based on the patient's condition, usually 1 to 6 courses. The Chinese medicine granules have a uniform and good therapeutic effect on patients with different levels of reflux esophagitis and are not prone to recurrence after treatment. The following is an example of a typical case: (1) Mr. Li, born in 1982, is a sales manager from Shenyang, Liaoning Province. He visited Yingshi TCM Clinic in Nanguan District, Changchun City in May 2023. The patient had repeated acid reflux and heartburn for 2 years, especially after meals and when he was nervous. He also had epigastric distension, frequent belching, and a feeling of fullness in the ribs. He was under great work pressure and easily irritable. His tongue was reddish, with a thin white and slightly yellow fur and a stringy pulse. He was diagnosed with reflux esophagitis after examination, and the RE grade was determined to be A by electronic gastroscopy. TCM diagnosis: liver-stomach disharmony. He was orally administered the Chinese medicine granules of Example 2 of the present invention, 10 g each time, 2 times / d. After 2 weeks of treatment, the frequency of acid reflux and heartburn was reduced, and the belching and rib distension were reduced. After continuing the treatment for 6 weeks, the epigastric distension was basically gone, and the acid reflux and heartburn only occurred slightly when he was eating carelessly or was extremely anxious. Follow-up until July 2024 showed that the condition was stable, with no obvious recurrence, and electronic gastroscopy examination showed no mucosal damage.

[0059] (2) Ms. Zhang, born in 1975, is a middle school teacher from Harbin, Heilongjiang Province. She visited Yingshi TCM Clinic in Nanguan District, Changchun City in September 2022. One and a half years ago, she began to experience burning pain behind the sternum, acid regurgitation, and a foreign body sensation in the throat after a quarrel over trivial matters at home. These symptoms were often triggered or aggravated by mood swings or eating a slightly full meal. She also had loss of appetite, sighing, a pale red tongue, a thin white fur, and a stringy and thin pulse. She was diagnosed with reflux esophagitis after examination, and the RE grade was determined to be B by electronic gastroscopy. TCM diagnosis: liver-stomach disharmony syndrome. Oral administration of the Chinese medicine granules of Example 2 of the present invention, 10 g each time, 2 times / d; after 3 weeks of treatment, the burning pain behind the sternum was relieved, the frequency of acid reflux was reduced, the foreign body sensation in the throat and belching were improved, and the mood was slightly relieved; after 5 courses of treatment, the main symptoms basically disappeared, and the appetite was restored; follow-up to March 2024, occasional mild acid reflux due to fatigue or anger, but the degree was mild and the time was short, and it did not affect life, and the electronic gastroscopy examination was grade A.

[0060] (3) Mr. Chen, born in 1968, is a self-employed person from Jilin City, Jilin Province. He visited Yingshi TCM Clinic in Nanguan District, Changchun City in January 2024. Three years ago, he began to experience acid reflux and heartburn after meals and at night, accompanied by noisy discomfort in the epigastric area, and sometimes bloating and pain extending to the flanks. He was irritable and often lost his temper over trivial matters. He had taken Western medicine acid suppressants, which were effective in the early stages but recurred easily after discontinuation of the medication. His tongue was slightly red, with a thin yellow fur and a stringy and rapid pulse. He was diagnosed with reflux esophagitis after examination, and the electronic gastroscopy confirmed that the RE grade was B. TCM diagnosis: liver-stomach disharmony syndrome. The Chinese medicine granules of Example 2 of the present invention were taken orally, 10 g each time, 2 times / d; after 2 weeks of treatment, acid reflux, heartburn and noisy feeling were alleviated, flank pain was relieved, and the mood was slightly stable; after 4 courses of treatment, nocturnal reflux was basically controlled, and epigastric discomfort was significantly alleviated; a total of 6 courses of treatment were given, the clinical symptoms disappeared, and the mood was stable; follow-up to May 2025 showed no recurrence, and no damage was found during electronic gastroscopy.

[0061] (4) Ms. Liu, born in 1990, is a designer from Hohhot, Inner Mongolia Autonomous Region. She visited Yingshi TCM Clinic in Nanguan District, Changchun City in July 2023. Six months after giving birth, the patient began to experience frequent belching, acid reflux, pharyngeal obstruction due to childcare anxiety. She also experienced obvious epigastric distension after eating. She also experienced breast pain and poor sleep. Her tongue was pale red, with a thin white fur and a stringy pulse. She was diagnosed with reflux esophagitis after examination. TCM diagnosis: liver-stomach disharmony syndrome. She was orally administered the Chinese medicine granules of Example 2 of the present invention, 10 g each time, twice a day. After one week of treatment, her belching and bloating were significantly relieved, her acid reflux was reduced, her sleep improved, and her breast pain was relieved. After one month of treatment, her pharyngeal obstruction disappeared, her mood improved, and her main symptoms were basically under control. She was followed up until December 2024 and her condition was stable, with occasional mild belching and no other discomfort.

[0062] (5) Mr. Zhao, born in 1955, is from Dalian, Liaoning Province, and is retired. He went to Yingshi Traditional Chinese Medicine Clinic in Nanguan District, Changchun for treatment in November 2022. The patient had repeated acid reflux, heartburn, and dull pain behind the sternum for the past 4 years, which was often aggravated by quarrels with children or excessive thinking. He also had abdominal distension, poor appetite, and fatigue. He had a history of hypertension, which was well controlled. His tongue was pale with teeth marks on the edges, a thin white fur, and a weak and stringy pulse. After examination, he was diagnosed with reflux esophagitis, and an electronic gastroscopy determined that the RE grade was Class C. Traditional Chinese Medicine diagnosis: liver-stomach disharmony syndrome. He took the Chinese medicine granules of Example 2 of the present invention orally, 10 g each time, 2 times / d. After 10 days of treatment, the number of acid reflux and heartburn attacks decreased, chest pain was relieved, appetite was slightly improved, and his spirits improved. After 3 courses of treatment, the abdominal distension and fatigue were significantly relieved. After five courses of treatment, the patient's clinical symptoms essentially disappeared, his mood stabilized, and his physical strength recovered. Follow-up until October 2024 showed that his condition was stable with no recurrence, and electronic gastroscopy examination showed grade A.

[0063] The above description is a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating reflux esophagitis of liver-stomach disharmony type, characterized in that: The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 6-12 parts of green peel, 6-12 parts of dried tangerine peel, 6-12 parts of peony bark, 5-10 parts of magnolia bark, 6-12 parts of qinpi, 5-10 parts of calcined walnut seeds, 5-10 parts of cuttlefish bone, 3-9 parts of ginger, 5-10 parts of sandalwood, 8-15 parts of salvia miltiorrhiza, 8-15 parts of calcined oyster shell, 5-10 parts of bitter orange, 5-9 parts of stove core soil, and 8-15 parts of sea clam shell.

2. A Chinese medicine composition for treating reflux esophagitis of liver-stomach disharmony type according to claim 1, characterized in that: The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 6-12 parts of green peel, 10-12 parts of dried tangerine peel, 8-12 parts of moutan bark, 7-10 parts of magnolia bark, 10-12 parts of qinpi, 6-10 parts of calcined walnut seeds, 8-10 parts of cuttlefish bone, 5-9 parts of ginger, 6-10 parts of sandalwood, 10-15 parts of salvia miltiorrhiza, 10-15 parts of calcined oyster shell, 6-10 parts of bitter orange immature fruit, 7-9 parts of stove core soil, and 10-15 parts of sea clam shell.

3. A Chinese medicine composition for treating reflux esophagitis of liver-stomach disharmony type according to claim 2, characterized in that: The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 10-12 parts of green peel, 10-12 parts of dried tangerine peel, 8-10 parts of moutan bark, 7-8 parts of magnolia bark, 10-12 parts of qinpi, 8-10 parts of calcined citrus fruit, 8-10 parts of cuttlefish bone, 8-9 parts of ginger, 8-10 parts of sandalwood, 10-15 parts of salvia miltiorrhiza, 12-15 parts of calcined oyster shell, 6-10 parts of bitter orange, 8-9 parts of stove core soil, and 12-15 parts of sea clam shell.

4. Use of the traditional Chinese medicine composition for treating liver-stomach disharmony type reflux esophagitis according to any one of claims 1 to 3 in the preparation of a medicament for treating liver-stomach disharmony type reflux esophagitis.

5. The use according to claim 4, characterized in that The dosage form of the drug for treating liver-stomach disharmony type reflux esophagitis is an oral preparation, and the oral preparation is selected from any one of granules, tablets, capsules, powders, oral liquids or pills.

6. A Chinese medicine granule for treating reflux esophagitis of liver-stomach disharmony type, characterized in that: The Chinese medicine granules include the following raw materials by weight: 6-12 grams of green peel, 6-12 grams of dried tangerine peel, 6-12 grams of peony bark, 5-10 grams of magnolia bark, 6-12 grams of qinpi, 5-10 grams of calcined corrugated fruit, 5-10 grams of cuttlefish bone, 3-9 grams of ginger, 5-10 grams of sandalwood, 8-15 grams of salvia miltiorrhiza, 8-15 grams of calcined oyster shell, 5-10 grams of immature bitter orange, 5-9 grams of stove heart soil, and 8-15 grams of sea clam shell; The preparation method of the Chinese medicine granules comprises the following steps: Step 1. Process the green peel and the tangerine peel together, grind them into coarse powder, sieve them, mix the coarse powder with enzyme solution for enzymolysis, then add water for decoction, filter and extract the juice, dry, grind and sieve them to obtain dry extract powder for later use; Step 2. Slice the cortex qinpi and the cortex moutan, soak them, extract them at 80°C, filter them while keeping them warm, concentrate them under reduced pressure, freeze them to form a brittle solid, and grind them with air flow to obtain a dry extract powder for later use; Step 3. Crush the Magnolia officinalis to a coarse powder and sieve; crush the Citrus aurantium immaturus shell; mix the two, add 50% ethanol, and perform ultrasonic-microwave synergistic extraction at room temperature; slice the Salvia miltiorrhiza, add 50% ethanol, and perform ultrasonic-microwave synergistic extraction at 60°C. After cooling, filter the extract, combine it with the Magnolia officinalis and Citrus aurantium immaturus extracts, and concentrate under reduced pressure to obtain an extract. After that, add microcrystalline cellulose, spray dry, and obtain a powder for later use; Step 4. Calcined corrugated paper is quenched with 20% rice vinegar, air-dried, air-pulverized, and ball-milled to 300-500 nm. Calcined oysters are quenched with 20% rice vinegar until crisp, air-dried, air-pulverized, separated by a classifier, and passed through a 325-mesh sieve for later use. Cuttlefish bones are boiled in a 2% NaOH solution at 80°C for 1 hour, washed with water until neutral, soaked in 5% acetic acid for 1 hour, washed with water to a pH of 6.5-7.0, air-dried, and air-pulverized to a D50 of 5 μm. Sea clam shells are softened and calcined at 150°C, added to 20% rice vinegar, stirred until free of bubbles, filtered, passed through a 200-mesh sieve, added to a PVP-K30 aqueous solution, stirred in a 60°C water bath, vacuum-filtered, and ball-milled to a D90 of ≤400 nm. Hearth soil is boiled in 10% hydrochloric acid, washed with water to a pH of 6.0, calcined at 750°C for 4 hours, and air-pulverized to a D90 of ≤2 μm. The above five ultrafine powders are mixed and set aside. Step 5. Slice ginger, extract with supercritical CO2, and collect ginger volatile oil; crush sandalwood to obtain coarse powder, sieve, extract with supercritical CO2, and collect sandalwood volatile oil; combine ginger volatile oil and sandalwood volatile oil, then include them in a ratio of oil:β-cyclodextrin = 1:6, stir, and spray dry to obtain inclusion compound powder; Step 6. Mix the powders obtained in step 1, step 2, step 3 and step 5, spray with 8% ethanol to moisten, add the mixed powder obtained in step 4, add starch and dextrin, mix well, roll and form granules by dry method.

7. The Chinese medicine granules for treating reflux esophagitis of liver-stomach disharmony type according to claim 6, characterized in that: The enzyme in the enzyme solution in step 1 is cellulase.

8. The Chinese medicine granules for treating reflux esophagitis of liver-stomach disharmony type according to claim 6, characterized in that: In step 3, 15% of the amount of microcrystalline cellulose extract was added and the mixture was spray-dried at 135°C.

9. The Chinese medicine granules for treating reflux esophagitis of liver-stomach disharmony type according to claim 6, characterized in that: In step 5, the ginger is sliced ​​and then subjected to supercritical CO2 extraction at 35° C. and 20 MPa; the sandalwood is crushed into coarse powder and passed through a 20-mesh sieve, and then subjected to supercritical CO2 extraction at 40° C. and 25 MPa.

10. The Chinese medicine granules for treating reflux esophagitis of liver-stomach disharmony type according to claim 6, characterized in that: In step 6, 40% of the main drug amount of starch and dextrin is added in a ratio of 1:1.

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