Traditional Chinese medicine compositions and granules for treating reflux esophagitis due to liver-stomach disharmony

Abstract

This invention belongs to the field of traditional Chinese medicine compositions, and relates to a traditional Chinese medicine composition and granules for treating reflux esophagitis of the liver-stomach disharmony type. The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 6-12 parts green tangerine peel, 6-12 parts dried tangerine peel, 6-12 parts peony bark, 5-10 parts magnolia bark, 6-12 parts fraxinus bark, 5-10 parts calcined oyster shell, 5-10 parts cuttlebone, 3-9 parts fresh ginger, 5-10 parts sandalwood, 8-15 parts salvia miltiorrhiza, 8-15 parts calcined oyster shell, 5-10 parts immature bitter orange, 5-9 parts hearth soil, and 8-15 parts clam shell. This traditional Chinese medicine composition uses green tangerine peel, immature bitter orange, calcined oyster shell, and cuttlebone as the principal herbs; tangerine peel, magnolia bark, calcined oyster shell, clam shell, sandalwood, peony bark, and fraxinus bark as the assistant herbs; and salvia miltiorrhiza, calcined clay, and ginger as adjuvant herbs. The entire formula works by soothing the liver and relieving depression, regulating qi and harmonizing the stomach to regulate the fundamental qi mechanism, reducing reflux and neutralizing acid to treat the symptoms of reflux, and supplementing with heat-clearing and blood-stasis-removing to eliminate the transformation of stagnant heat and blood stasis. At the same time, it also takes into account warming the middle and harmonizing the stomach and protecting the mucosa. It can achieve good therapeutic effects when used alone, and has the advantages of rapid onset of action, stable efficacy, high total effective rate, and low recurrence rate.

Description

Technical Field

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

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

[0003] The incidence of reflux esophagitis (RE) in China is showing an increasing trend year by year, with a prevalence of approximately 10%-20% in the general population. The incidence is higher in urban areas than in rural areas due to factors such as high work pressure, irregular eating habits, and sedentary lifestyles. Traditional Chinese medicine classifies reflux esophagitis into four types: liver-stomach stagnation with heat, liver-stomach disharmony, spleen deficiency with stomach heat, spleen deficiency with qi stagnation, and qi deficiency with blood stasis. Among these, liver-stomach disharmony accounts for a relatively high proportion of reflux esophagitis patients, especially those aged 20-50.

[0004] Commonly used medications for treating reflux esophagitis include omeprazole, pantoprazole, cimetidine, nizatidine, and domperidone. However, these medications primarily treat the symptoms, have low overall efficacy, are prone to recurrence, and have significant side effects. Traditional Chinese medicine formulas such as Zuojin Wan have the effects of clearing liver fire, relieving nausea and vomiting, and treating liver fire invading the stomach syndrome, characterized by symptoms such as hypochondriac pain, vomiting, bitter taste in the mouth, heartburn, and acid reflux. Currently, it is mainly used for acute and chronic gastritis, gastric ulcers, and other conditions where liver fire invading the stomach is present. The modified Zuojin Wan formula adds Chuandongzi to the original formula to regulate qi and relieve pain, Xiangfu to soothe the liver and regulate qi, Banxia to relieve nausea and vomiting, Chenpi to regulate qi and strengthen the spleen, Shengjiang to warm the middle jiao and stop vomiting, Fuling to strengthen the spleen and harmonize the middle jiao, Baishao to soften the liver and nourish liver blood, and Gancao to strengthen the spleen and stomach, relieve liver tension, and harmonize the other herbs. The entire formula works together to clear liver fire and harmonize the stomach, allowing liver fire to be cleared and stomach qi to be lowered. The combination of Jiawei Zuojin Pills with rabeprazole sodium enteric-coated capsules and domperidone tablets has a good therapeutic effect on reflux esophagitis, with a total effective rate as high as 95.5%. However, Jiawei Zuojin Pills are bitter and cold in nature, and long-term use can easily damage the spleen and stomach's yang energy. Rabeprazole, when used long-term, can easily cause gastrointestinal discomfort. Furthermore, the combined use of these three drugs requires frequent and high-dose administration. Therefore, it is necessary to provide a traditional Chinese medicine composition that does not require combination with Western medicine and has a good therapeutic effect on reflux esophagitis caused by liver-stomach disharmony. Summary of the Invention

[0005] In view of the shortcomings and deficiencies of existing technologies, the purpose of this invention is to provide a traditional Chinese medicine composition for treating reflux esophagitis of the liver-stomach disharmony type. This composition contains *Fraxinus chinensis* bark and *Paeonia suffruticosa* bark, which clear heat without being overly cold; calcined clay combined with ginger can improve stomach pain and loose stools caused by long-term use of bitter and cold medicines; and calcined oyster shell, cuttlebone, calcined oyster shell, and clam shell, used together, have a calcium carbonate content of over 60%, which neutralizes stomach acid 2-3 times more efficiently than any single herb. Furthermore, the amino acid components of cuttlebone 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 traditional Chinese medicine composition has been shown to achieve good therapeutic effects when used alone, and it has advantages such as rapid onset of action, stable efficacy, high overall effective rate, and low recurrence rate in treating reflux esophagitis of the liver-stomach disharmony type.

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

[0007] A traditional Chinese medicine composition for treating reflux esophagitis of the liver-stomach disharmony type, the composition comprising the following raw materials in parts by weight: 6-12 parts green tangerine peel, 6-12 parts dried tangerine peel, 6-12 parts peony bark, 5-10 parts magnolia bark, 6-12 parts fraxinus bark, 5-10 parts calcined oyster shell, 5-10 parts cuttlebone, 3-9 parts fresh ginger, 5-10 parts sandalwood, 8-15 parts salvia miltiorrhiza, 8-15 parts calcined oyster shell, 5-10 parts immature bitter orange, 5-9 parts hearth soil, and 8-15 parts clam shell.

[0008] As a preferred embodiment of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 6-12 parts green tangerine peel, 10-12 parts dried tangerine peel, 8-12 parts peony bark, 7-10 parts magnolia bark, 10-12 parts fraxinus bark, 6-10 parts calcined oyster shell, 8-10 parts cuttlebone, 5-9 parts fresh ginger, 6-10 parts sandalwood, 10-15 parts salvia miltiorrhiza, 10-15 parts calcined oyster shell, 6-10 parts immature bitter orange, 7-9 parts hearth soil, and 10-15 parts clam shell.

[0009] As a preferred embodiment of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 10-12 parts green tangerine peel, 10-12 parts dried tangerine peel, 8-10 parts peony bark, 7-8 parts magnolia bark, 10-12 parts fraxinus bark, 8-10 parts calcined oyster shell, 8-10 parts cuttlebone, 8-9 parts fresh ginger, 8-10 parts sandalwood, 10-15 parts salvia miltiorrhiza, 12-15 parts calcined oyster shell, 6-10 parts immature bitter orange, 8-9 parts hearth soil, and 12-15 parts clam shell.

[0010] The traditional Chinese medicine composition provided by this invention has been proven through clinical trials to have good therapeutic effects on different grades of reflux esophagitis caused by liver-stomach disharmony, with a total effective rate of up to 95%. Moreover, it 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, this traditional Chinese medicine composition can be used in the preparation of drugs for treating reflux esophagitis caused by liver-stomach disharmony.

[0011] The dosage form of the drug for treating reflux esophagitis of the liver-stomach disharmony type according to the present invention is an oral preparation, which is selected from any one of granules, tablets, capsules, powders, oral liquids or pills.

[0012] This invention also provides a traditional Chinese medicine granule for treating reflux esophagitis of the liver-stomach disharmony type, the traditional Chinese medicine granule comprising the following raw materials by weight: green tangerine peel 6-12, dried tangerine peel 6-12, peony bark 6-12, magnolia bark 5-10, fraxinus bark 6-12, calcined oyster shell 5-10, cuttlebone 5-10, fresh ginger 3-9, sandalwood 5-10, salvia miltiorrhiza 8-15, calcined oyster shell 8-15, immature bitter orange 5-10, hearth soil 5-9, and clam shell 8-15;

[0013] The preparation method of the traditional Chinese medicine granules includes the following steps:

[0014] Step 1. Process green tangerine peel and dried tangerine peel together, mix and grind into coarse powder, sieve, mix coarse powder with enzyme solution for enzymatic hydrolysis, then add water and decoct, press and filter to extract juice, dry, grind, sieve, and obtain dry extract powder for later use.

[0015] Step 2. Slice the bark of Qinpi and the bark of Mudanpi, soak them, extract them at 80℃, filter them while keeping them warm, concentrate them under reduced pressure, freeze the resulting extract to form a brittle solid, pulverize them with airflow to obtain a dry extract powder for later use.

[0016] Step 3. Crush Magnolia officinalis into coarse powder and sieve; crush Citrus aurantium into powder; mix the two together and add 50% ethanol for ultrasonic-microwave co-extraction at room temperature; slice Salvia miltiorrhiza, add 50% ethanol for ultrasonic-microwave co-extraction at 60℃, cool and filter finely, combine with the extract of Magnolia officinalis and Citrus aurantium, concentrate under reduced pressure, add microcrystalline cellulose, spray dry to obtain powder for later use;

[0017] Step 4. Calcined corrugated iron was quenched with 20% rice vinegar, dried by forced air, pulverized by air jet milling, and ball milled to 300-500 nm. Calcined oyster shell was quenched with 20% rice vinegar until brittle, dried by forced air, pulverized by air jet milling, separated by a classifier wheel, and passed through a 325-mesh sieve for later use. Cuttlebone was boiled in 2% NaOH solution at 80℃ for 1 hour, washed with water until neutral, soaked in 5% acetic acid for 1 hour, washed with water until pH 6.5-7.0, dried by forced air, and pulverized by air jet milling to D50=5μm. Clam shells were softened and calcined at 150℃, added to 20% rice vinegar, stirred until no bubbles were observed, filtered, passed through a 200-mesh sieve, added to PVP-K30 aqueous solution, stirred in a water bath at 60℃, vacuum filtered, and ball milled to D90≤400nm. Hearth soil was boiled in 10% hydrochloric acid, washed with water until pH 6.0, calcined at 750℃ for 4 hours, and pulverized by air jet milling to D90≤2μm. The above five ultrafine powders were mixed and set aside.

[0018] Step 5. Slice ginger, extract with supercritical CO2, and collect ginger volatile oil; crush sandalwood into coarse powder, sieve, extract with supercritical CO2, and collect sandalwood volatile oil; combine ginger volatile oil and sandalwood volatile oil, then incorporate them at an oil:β-cyclodextrin ratio of 1:6, stir, and spray dry to obtain incorporation powder;

[0019] Step 6. Mix the powders obtained in Steps 1, 2, 3 and 5, wet with 8% ethanol, add the mixed powder obtained in Step 4, add starch and dextrin, mix well, roll and dry to form granules.

[0020] As a preferred embodiment of the present invention, the enzyme in the enzyme solution in step 1 is cellulase.

[0021] As a preferred embodiment of the present invention, in step 3, 15% microcrystalline cellulose is added and spray-dried at 135°C.

[0022] As a preferred embodiment of the present invention, in step 5, the ginger slices are extracted using supercritical CO2 at 35°C and 20MPa; the sandalwood is crushed into coarse powder and passed through a 20-mesh sieve, then extracted using supercritical CO2 at 40°C and 25MPa.

[0023] As a preferred embodiment of the present invention, in step 6, starch and dextrin are added at a ratio of 1:1, with 40% of the amount of the main drug.

[0024] The traditional Chinese medicine composition provided by this invention contains: Green tangerine peel (Citrus reticulata peel): bitter, pungent, and warm; it enters the liver, gallbladder, and stomach meridians, soothing the liver, dispersing qi stagnation, and resolving stagnation. Liver-stomach disharmony is primarily characterized by liver qi stagnation. Green tangerine peel, being pungent and bitter, specifically enters the liver meridian, effectively breaking up liver qi stagnation, smoothing qi flow, and relieving chest and rib pain and epigastric fullness. Entering the stomach meridian, it can resolve stagnation, assist stomach qi in descending rebellious qi, and is effective for epigastric fullness and frequent belching caused by qi stagnation in reflux esophagitis. Furthermore, green tangerine peel contains limonene volatile oil, flavonoids (hesperidin), alkaloids, etc. The volatile oil can promote gastrointestinal motility, relax smooth muscle, and relieve spasms; the flavonoids have anti-inflammatory and gastrointestinal motility-regulating effects.

[0025] Dried tangerine peel: pungent, bitter, and warm in nature; it enters the spleen and lung meridians; it regulates qi and strengthens the spleen, dries dampness and resolves phlegm; when used in combination with green tangerine peel, dried tangerine peel is more effective in regulating the qi of the spleen and stomach, drying dampness and resolving phlegm, relieving epigastric fullness, nausea, and acid reflux caused by spleen deficiency and dampness; it is warm but not drying, able to both regulate qi and harmonize the stomach and relieve nausea, targeting the symptoms of spleen and stomach qi stagnation and phlegm-dampness obstruction in reflux esophagitis. The main components of dried tangerine peel are hesperidin, hesperidin oil, limonene, and vitamin C; hesperidin can protect the gastric mucosa and inhibit excessive gastric acid secretion; volatile oils can promote the secretion of digestive juices, enhance gastrointestinal motility, and regulate gastrointestinal function.

[0026] Moutan bark: bitter, pungent, slightly cold; enters the heart, liver, and kidney meridians; clears heat and cools the blood, invigorates blood circulation and removes blood stasis, reduces deficiency heat; prolonged disharmony between the liver and stomach easily generates heat, scorching the stomach collaterals, resulting in heat symptoms such as heartburn and burning pain in the stomach; Moutan bark, being bitter and cold, clears heat, clears stagnant heat in the blood, and relieves acid reflux and heartburn caused by stomach heat; its blood-invigorating and blood-stasis-removing effects can improve esophageal mucosal congestion and edema, and promote damage repair; Moutan bark contains paeonol, paeonoside, paeoniflorin, etc.; paeonol has anti-inflammatory, analgesic, and anti-ulcer effects, can inhibit gastric acid secretion, and reduce gastric mucosal inflammation; the blood-invigorating and blood-stasis-removing components can improve local blood circulation and promote tissue repair.

[0027] Magnolia officinalis: bitter, pungent, and warm; enters the spleen, stomach, lung, and large intestine meridians; dries dampness and eliminates phlegm, lowers qi and relieves fullness; for those with liver and stomach disharmony accompanied by dampness and turbidity obstructing the middle jiao, Magnolia officinalis, being bitter and warm, dries dampness, and pungent and warm, promotes qi circulation. It can both resolve dampness and turbidity in the spleen and stomach and regulate the qi of the stomach and intestines, relieving symptoms such as abdominal distension, nausea, vomiting, and constipation; its function of lowering qi and relieving fullness can help the stomach qi descend and reduce acid reflux; Magnolia officinalis contains honokiol, magnolol, volatile oils, etc.; honokiol has anti-ulcer, anti-inflammatory, and antibacterial effects, can inhibit Helicobacter pylori, regulate the tone of gastrointestinal smooth muscle, promote gastric emptying, and reduce reflux.

[0028] Fraxinus bark: bitter, astringent, and cold; enters the liver, gallbladder, and large intestine meridians; clears heat and dries dampness, astringes and stops diarrhea, and improves eyesight; in reflux esophagitis, the bitter and cold nature of Fraxinus bark clears heat, effectively clearing damp-heat in the liver, gallbladder, and large intestine, targeting bitter taste, acid reflux, and burning pain in the stomach caused by liver and stomach heat stagnation; its astringent taste can astringe the mucosa and relieve the burning sensation after esophageal mucosal damage, similar to the effect of "clearing heat and astringing sores"; Fraxinus bark contains fraxin A, fraxin B, aescin, aescin lactone, and other coumarin components; these components have anti-inflammatory, antibacterial, and antioxidant effects, which can reduce esophageal mucosal inflammation and promote ulcer healing.

[0029] Calcined oyster shell: Salty, neutral; enters the lung, stomach, and liver meridians; resolves phlegm and softens hard masses, neutralizes acid and relieves pain; calcined oyster shell, being salty and cold, enters the stomach and is good at neutralizing stomach acid, making it a commonly used medicine for treating acid reflux and heartburn; its hard texture, after calcination, can neutralize stomach acid and relieve the irritation of stomach acid on the esophageal mucosa, while also entering the liver meridian, it can soothe the liver and regulate qi, making it suitable for those with liver and stomach disharmony combined with excessive stomach acid; the main components of calcined oyster shell are calcium carbonate, trace elements such as iron and zinc; calcium carbonate can neutralize stomach acid, increase the pH value in the stomach, and reduce reflux symptoms; its trace elements may participate in mucosal repair.

[0030] Cuttlebone: Salty, astringent, and warm; enters the spleen, stomach, and kidney meridians; astringes and stops bleeding, stops seminal emission and leukorrhea, neutralizes acid and relieves pain, promotes wound healing and tissue regeneration; cuttlebone has significant acid-neutralizing and analgesic effects, neutralizing stomach acid and astringing and protecting the esophageal and gastric mucosa, promoting ulcer healing; its astringent taste can astringe dissipated qi, and when combined with liver-soothing and qi-regulating drugs, it enhances the effect of harmonizing the stomach and suppressing nausea, making it suitable for those with acid reflux, epigastric pain, and mucosal damage; the main components of cuttlebone are calcium carbonate, chitin, amino acids, etc.; calcium carbonate neutralizes stomach acid, chitin can form a protective film on the mucosal surface, amino acids promote tissue repair, and its gelatinous components can protect the esophageal mucosa.

[0031] Ginger: pungent and warm; enters the lung, spleen, and stomach meridians; relieves exterior syndromes and dispels cold, warms the middle jiao and stops vomiting, resolves phlegm and stops coughing; ginger is a "holy medicine for vomiting," warms the stomach and dispels cold, harmonizes the middle jiao and relieves nausea, vomiting, and watery reflux caused by disharmony between the liver and stomach and stomach cold; its pungent and warm nature can counteract the cooling and suppressing effects of bitter and cold medicines, harmonize various medicines, and enhance the digestive function of the spleen and stomach; ginger contains gingerol, gingerol, gingerene, gingerol volatile oil, gingerene, 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 blood circulation in the gastric mucosa.

[0032] Sandalwood: pungent, warm; enters the spleen, stomach, and lung meridians; promotes qi circulation, warms the middle jiao, and relieves stomach pain; sandalwood is pungent, warm, and aromatic, and is good at regulating qi stagnation in the spleen and stomach, warming the middle jiao and promoting qi circulation, relieving cold pain and bloating in the stomach, especially suitable for those with liver-stomach disharmony and stomach cold; it promotes qi circulation without depleting qi, and warms without being drying, which can enhance the qi-regulating effects of tangerine peel and green tangerine peel, while relieving stomach pain and improving appetite; sandalwood contains volatile oil components such as santalol, santalene, and sandalwood oil; santalol can regulate gastrointestinal nerve function, relieve smooth muscle spasms, and reduce stomach pain; volatile oils can promote the secretion of digestive juices and enhance gastrointestinal motility.

[0033] Danshen (Salvia miltiorrhiza): Bitter, slightly cold; enters the heart and liver meridians; invigorates blood circulation and removes blood stasis, unblocks meridians and relieves pain, clears the heart and relieves irritability, cools the blood and eliminates carbuncles; chronic reflux esophagitis easily leads to blood stasis, esophageal mucosal congestion, edema and even erosion. Danshen invigorates blood circulation and removes blood stasis, improves local blood circulation in the esophagus and promotes mucosal repair; its slightly cold nature can clear heat stagnation 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, tanshinone, salvianolic acid B, etc.; tanshinone IIA can resist inflammation and ulcers and improve microcirculation; salvianolic acid B has antioxidant effects, protects the gastric mucosa and promotes the repair of damaged tissues.

[0034] Calcined oyster shell: Salty, slightly cold; enters the liver and kidney meridians; it subdues yang and nourishes yin, calms the mind, softens and disperses nodules, astringes and consolidates, neutralizes acid and relieves pain; calcined oyster shell is salty, cold and heavy, with strong acid-neutralizing and analgesic effects, which can neutralize stomach acid and relieve heartburn and acid reflux; its astringent and consolidating effects can protect the esophageal mucosa and reduce the stimulation of the mucosa by gastric acid reflux, making it suitable for those with excessive stomach acid and mucosal damage; in addition, its strong calming properties can lower the upward rebellious stomach qi and help the qi to descend; the main components of calcined oyster shell are calcium carbonate, calcium phosphate, amino acids, etc.; calcium carbonate neutralizes stomach acid, amino acids promote mucosal repair, and its trace elements (such as zinc and copper) participate in enzyme synthesis and enhance tissue repair ability.

[0035] Fructus Aurantii Immaturus (Zhi Shi): Bitter, pungent, sour, slightly cold; enters the spleen and stomach meridians; breaks up qi stagnation, resolves phlegm and dissipates lumps; Fructus Aurantii Immaturus is pungent and bitter, with a strong ability to break up qi stagnation and dissipate lumps. It can regulate the qi of the stomach and intestines, promote gastrointestinal motility, eliminate abdominal distension, accelerate gastric emptying, and reduce gastric acid reflux; when combined with Pericarpium Citri Reticulatae (Qing Pi) and Pericarpium Citri Reticulatae (Chen Pi), it enhances the effects of soothing the liver and regulating qi, harmonizing the stomach and suppressing rebellious qi, and is effective for lumps, belching, and reflux caused by liver and stomach disharmony; Fructus Aurantii Immaturus contains volatile oils (such as limonene), flavonoids (such as hesperidin), synephrine, etc.; synephrine can stimulate α receptors, enhance the contractility of gastrointestinal smooth muscle, and promote gastric emptying; flavonoids regulate gastrointestinal motility, have anti-inflammatory effects, and protect the gastric mucosa.

[0036] Stove core soil: pungent and warm; enters the spleen and stomach meridians; warms the middle jiao to stop bleeding, stops vomiting, and stops diarrhea; pungent and warm, stove core soil enters the spleen and stomach, effectively warming the middle jiao and harmonizing the stomach, suppressing nausea and vomiting, and is suitable for those with liver and stomach disharmony and spleen and stomach deficiency and cold, relieving symptoms such as vomiting clear water, dull stomach pain, and loose stools; its adsorption effect can reduce the stimulation of gastric acid on the mucosa, while astringing and stopping bleeding, making it suitable for those with reflux esophagitis complicated by mucosal bleeding; stove core soil is mainly composed of silicates, calcium, iron, aluminum and other minerals, as well as organic matter; minerals can neutralize gastric acid and adsorb harmful substances in the stomach, while organic matter has the effect of protecting the gastric mucosa and promoting ulcer healing.

[0037] Clam shells: Salty and cold in nature; enters the lung and stomach meridians; clears heat and resolves phlegm, softens and disperses nodules, neutralizes acid and relieves pain; the salty and cold nature of clam shells enters the stomach, clearing stomach heat and resolving heat phlegm, targeting heartburn, bitter taste in the mouth, and sticky phlegm caused by liver and stomach heat; it can also neutralize acid and relieve pain, neutralize stomach acid, and alleviate acid reflux symptoms; its ability to soften and disperse nodules can improve tissue hyperplasia or adhesions after esophageal mucosal inflammation, and is suitable for reflux esophagitis with obvious heat symptoms; the main components of clam shells are calcium carbonate, chitin, amino acids, etc.; calcium carbonate neutralizes stomach acid, chitin protects the mucosa, and its cold components can inhibit stomach heat and relieve burning sensation.

[0038] This formula uses green tangerine peel, immature bitter orange, calcined oyster shell, and cuttlebone as the principal herbs. Green tangerine peel is potent and specifically targets the liver and gallbladder, breaking up stagnation and soothing the liver, eliminating stagnation and relieving pain. It powerfully breaks up stagnation of qi in the liver meridian and relieves distending pain in the hypochondrium. Immature bitter orange is strong and enters the spleen and stomach meridians, breaking up stagnation and eliminating phlegm, dispersing lumps, lowering qi and relieving fullness, and guiding stomach qi downward. Calcined oyster shell and cuttlebone neutralize stomach acid and relieve pain, protect the mucosa. The two are often used together to enhance the acid-neutralizing effect, directly targeting the core pathogenesis of liver qi stagnation, rebellious invasion of the stomach, stomach disharmony, and qi rebellion with acid attacking the esophagus. The accompanying herbs, tangerine peel, regulate qi and strengthen the spleen, dry dampness and resolve phlegm, regulate spleen and stomach qi stagnation, promote digestion and prevent qi stagnation from generating phlegm and dampness; magnolia bark dries dampness and eliminates phlegm, lowers qi and relieves fullness, and suppresses rebellious qi; calcined oyster shell also has the effect of calming yang, and clam shell is cold in nature and can also clear heat, together enhancing the effects of neutralizing acid and relieving pain; sandalwood promotes qi and relieves pain, dispels cold and regulates the middle jiao, and clears the diaphragm and chest; peony bark clears heat and cools blood, invigorates blood and removes blood stasis, and fraxinus bark clears heat and dries dampness, assisting the principal herbs in clearing heat and blood stasis, and preventing heat evil from damaging yin and causing bleeding. Salvia miltiorrhiza is added to invigorate blood and remove blood stasis, unblock meridians and relieve pain, cool blood and relieve irritability; calcined clay and ginger work together to warm the middle jiao and stop bleeding, and suppress rebellious qi and stop vomiting, restraining the cold nature of fraxinus bark, peony bark, salvia miltiorrhiza, clam shell and other herbs in the formula, preventing excessive cold from damaging the stomach, and also protecting the astringent properties, thus protecting the mucous membrane. Ginger, because it warms the middle jiao and harmonizes the stomach, guides the medicinal power to the middle jiao spleen and stomach, and also has the function of guiding the medicine to the meridians. The formula works by soothing the liver and relieving depression, regulating qi and harmonizing the stomach to regulate the fundamental qi mechanism, reducing reflux and neutralizing acid to treat the symptoms of reflux, and supplementing with clearing heat and removing blood stasis to eliminate the transformation of stagnant heat and blood stasis. At the same time, it also takes into account warming the middle and harmonizing the stomach and protecting the mucous membrane. The formula is rigorous, layered, and highly targeted, reflecting the TCM ideas of "differentiation of syndromes and treatment" and "treating both the root cause and the symptoms".

[0039] Advantages and beneficial effects of the present invention:

[0040] (1) The traditional Chinese medicine composition provided by this invention contains Qinpi and Mudanpi, which clear heat without being too cold. The combination of hearth soil and ginger can improve the stomach pain and loose stools caused by long-term use of bitter and cold medicines. The four medicines, calcined oyster shell, cuttlebone, calcined oyster shell, and clam shell, have a calcium carbonate content of more than 60%, which is 2-3 times more effective in neutralizing gastric acid than the single medicine. Moreover, the amino acid components of cuttlebone 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 this traditional Chinese medicine composition can achieve good therapeutic effects when used alone. It has the advantages of rapid onset, stable efficacy, and high total effective rate in the treatment of reflux esophagitis of the liver-stomach disharmony type.

[0041] (2) The Chinese medicine granules provided by the present invention have the advantages of being highly pure, safe and effective, advanced in process, convenient to take and carry, and highly bioavailable, and are extremely competitive in the market. The granules are prepared using ultra-micro pulverization technology, with a volatile oil retention rate of 98%. Ultrasonic-microwave synergistic extraction results in a cell wall breakage rate of 95%. β-cyclodextrin inclusion and microencapsulation sustained release increase the solubility of poorly soluble components by 12 times and improve bioavailability by 2.5 times, significantly enhancing the therapeutic effect.

[0042] (3) The traditional Chinese medicine composition provided by the present invention regulates the fundamental function of Qi by soothing the liver and relieving depression, regulating Qi and harmonizing the stomach, treats the symptoms of reflux by reducing adverse reactions and neutralizing acid, and is supplemented by clearing heat and removing blood stasis to eliminate the changes of stagnation, heat and blood stasis. At the same time, it also takes into account warming the middle and harmonizing the stomach and protecting the mucosa. The formula is rigorous, layered, and highly targeted, reflecting the TCM ideas of "differentiation of syndromes and treatment" and "treating both the root cause and the symptoms". This formula does not need to be used with Western medicine. It has a good therapeutic effect on different grades of liver and stomach disharmony type reflux esophagitis, with a total effective rate of up to 95%.

[0043] (4) The traditional Chinese medicine composition provided by the present invention 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%. 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 esophageal mucosa to its normal barrier function, effectively block the erosion of gastric acid, pepsin and other refluxed substances, reduce the possibility of the esophagus being damaged again, and thus reduce the recurrence rate of reflux esophagitis. Detailed Implementation

[0044] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be described in further detail below. This description is only for explaining the invention and is not intended to limit the invention.

[0045] This invention discloses a traditional Chinese medicine composition, granules, and preparation method for treating reflux esophagitis of the liver-stomach disharmony type. Those skilled in the art can refer to the content of this document and appropriately modify the component parameters or process parameters to achieve the desired result. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included within the scope of protection of this invention.

[0046] Example 1:

[0047] This embodiment provides a traditional Chinese medicine composition for treating reflux esophagitis of the liver-stomach disharmony type. The traditional Chinese medicine composition is composed of the following raw materials by weight: 12 parts of green tangerine peel, 10 parts of dried tangerine peel, 10 parts of peony bark, 8 parts of magnolia bark, 12 parts of fraxinus bark, 8 parts of calcined oyster shell, 10 parts of cuttlebone, 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 hearth soil, and 12 parts of clam shell.

[0048] Example 2:

[0049] This embodiment provides a traditional Chinese medicine granule for treating reflux esophagitis of the liver-stomach disharmony type. The traditional Chinese medicine granule comprises the following raw materials by weight: 12 parts of green tangerine peel, 10 parts of dried tangerine peel, 10 parts of peony bark, 8 parts of magnolia bark, 12 parts of fraxinus bark, 8 parts of calcined oyster shell, 10 parts of cuttlebone, 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 hearth soil, and 12 parts of clam shell.

[0050] The preparation method of the traditional Chinese medicine granules includes the following steps:

[0051] Step 1. Process the green tangerine peel and dried tangerine peel together, mix and grind them into coarse powder, pass through a 10-mesh sieve, mix the coarse powder with enzyme solution at a material-to-liquid ratio of 1:10 (g / mL), adjust the pH of the system to 4.5 with 1 mol / L hydrochloric acid, place in a constant temperature water bath, and enzymatically hydrolyze for 1 hour at 50℃ with magnetic stirring (200 r / min); then add 10 times the amount of water and decoct, simmer for 1 hour, filter by pressure to obtain the juice, dry at -0.09 MPa and 60℃ in a vacuum belt dryer, then grind and pass through an 80-mesh sieve to obtain dried extract powder for later use;

[0052] 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 bio-enzyme first achieves gentle cell wall disruption, increasing the component extraction rate by 30%-40% while retaining more volatile active ingredients.

[0053] Step 2. Cut the fraxinus bark and peony bark into 1 mm slices; soak in cold water for 2 hours; combine the two and extract twice at 80℃, 1.5 hours each time; filter while maintaining the temperature to prevent the precipitation of components such as fraxin A from decreasing in solubility due to temperature drop below 60℃; concentrate under reduced pressure at 65℃ to a relative density of 1.25-1.30, and freeze the extract at -20℃ for 4 hours to form a brittle solid. Then, pulverize the extract at -20℃ with a low-temperature airflow with D90≤45μm to obtain a dried extract powder for later use.

[0054] Step 3. Crush Magnolia officinalis into coarse powder and pass it through a 30-mesh sieve; crush Citrus aurantium into powder; mix the two together and add 50% ethanol at a material-to-liquid ratio of 1:8. Set the microwave-ultrasound co-extraction instrument to 400W microwave + 40kHz and extract with ultrasound-microwave co-extraction for 30 minutes at room temperature; cut Salvia miltiorrhiza into 2mm slices, add 50% ethanol and extract with ultrasound-microwave co-extraction at 60℃ for 30 minutes (400W microwave + 40kHz), cool and filter finely, combine with the extracts of Magnolia officinalis and Citrus aurantium, concentrate under reduced pressure at 40℃ to a relative density of 1.25-1.30 extract, add 15% microcrystalline cellulose by weight of the extract, spray dry at 135℃ to obtain powder for later use;

[0055] Step 4. The calcined corrugated iron oxide is quenched three times with 20% rice vinegar (analytical grade) at a liquid-to-solid ratio of 1:1 (g / mL) to promote the release of trace elements such as magnesium, iron, and zinc from the mineral lattice, thereby increasing the bioavailability by about 1.5 times. Each time, the mixture is stirred for 30 minutes until no bubbles are present and the pH is adjusted to 8.0, which is close to the human body fluid environment, reducing irritation while retaining the ability to neutralize stomach acid. The mixture is then dried at 105℃ with forced air for 1 hour, with the moisture content controlled to ≤1.5%. After quenching, the fragments are air-jet pulverized to D90≤10μm and then ball-milled to 300-500nm. The powder is then collected.

[0056] Calcined oyster shells were quenched with 20% rice vinegar at a liquid-to-solid ratio of 1:1.5 (g / mL) until crisp, stirred for 30 minutes until no bubbles were present, and the pH was lowered to 8.0-8.5. They were then dried at 105℃ for 1 hour, pulverized by three cycles of airflow under a pressure of 0.5MPa, separated by a classifying wheel at 2800rpm, and passed through a 325-mesh sieve for later use.

[0057] Cuttlebone was boiled in 2% NaOH solution at 80℃ for 1 hour, achieving an organic matter removal rate of 92% and a calcium carbonate retention rate of ≥90%, with a pH value of 12.0-12.5. It was 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 in a forced-air dryer at 105℃ for 2 hours, and pulverized with supersonic airflow at -40℃ to a D50 of 5μm, and the powder was collected.

[0058] Clam shells were softened and calcined at 150℃ for 30 minutes to retain more than 95% calcium carbonate. 20% rice vinegar (analytical grade) was added at a ratio of 1:1 (g / mL), and stirred until no bubbles were observed (about 30 minutes). The pH was controlled at 9.0-9.5. After filtration, the mixture was passed through a 200-mesh sieve. 10% PVP-K30 (polyvinylpyrrolidone) aqueous solution was slowly added at a ratio of 2% (based on precipitated calcium carbonate). The mixture was stirred in a water bath at 60℃ for 2 hours, vacuum filtered, and then ground in a ball mill for 3 hours at a speed of 600 r / min. The particle size was measured to be D90≤400nm. The powder was then collected.

[0059] Boil the core soil in 10% hydrochloric acid for 30 minutes, wash with water until pH 6.0, calcine at 750℃ for 4 hours, and then pulverize it with airflow to D90≤2μm. Collect the powder, mix the above five ultrafine powders, and set aside for later use.

[0060] Step 5. Slice ginger and extract it using supercritical CO2 at 35℃ and 20MPa to collect the ginger volatile oil. The ginger volatile oil contains relatively stable amounts of gingerols, which are the main components of ginger that have the effect of dispelling cold and relieving nausea. Sandalwood is crushed into coarse powder and passed through a 20-mesh sieve. It is extracted using supercritical CO2 at 40℃ and 25MPa to collect the sandalwood volatile oil. The sandalwood volatile oil contains 60%-70% α-santalol, which has a central nervous system depressant and sedative effect. The ginger volatile oil and sandalwood volatile oil are combined and incorporated at an oil:β-cyclodextrin ratio of 1:6. The mixture is stirred at 40℃ for 2 hours and then spray-dried to obtain the incorporation powder.

[0061] Step 6. Mix the dried extract powders of green tangerine peel and dried tangerine peel from Step 1, the dried extract powders of peony bark and fraxinus bark from Step 2, the powders of magnolia bark, immature bitter orange, and salvia miltiorrhiza from Step 3, and the powders of ginger and sandalwood from Step 5 using a three-dimensional mixer. Spray with 8% ethanol to moisten. Add the ultrafine powders of calcined oyster shell, cuttlebone, calcined oyster shell, hearth soil, and clam shell from Step 4. Add 40% of the main drug amount of starch and dextrin at a 1:1 ratio and mix well. Roll press at 8MPa and dry process to make granules using a 16-mesh method.

[0062] Example 3:

[0063] The difference from Example 2 is that the Chinese herbal granules include the following raw materials by weight: 12 parts of green tangerine peel, 12 parts of dried tangerine peel, 8 parts of peony bark, 7 parts of magnolia bark, 10 parts of fraxinus bark, 10 parts of calcined oyster shell, 10 parts of cuttlebone, 9 parts of ginger, 10 parts of sandalwood, 15 parts of salvia miltiorrhiza, 15 parts of calcined oyster shell, 10 parts of immature bitter orange, 9 parts of hearth soil, and 15 parts of clam shell.

[0064] Example 4:

[0065] The difference from Example 2 is that the Chinese herbal granules include the following raw materials by weight: 6 parts of green tangerine peel, 6 parts of dried tangerine peel, 6 parts of peony bark, 5 parts of magnolia bark, 6 parts of fraxinus bark, 5 parts of calcined oyster shell, 5 parts of cuttlebone, 3 parts of ginger, 5 parts of sandalwood, 8 parts of salvia miltiorrhiza, 8 parts of calcined oyster shell, 5 parts of immature bitter orange, 5 parts of hearth soil, and 8 parts of clam shell.

[0066] Example 5:

[0067] The difference from Example 2 is that the Chinese herbal granules include the following raw materials by weight: 12 parts of green tangerine peel, 6 parts of dried tangerine peel, 10 parts of peony bark, 6 parts of magnolia bark, 8 parts of fraxinus bark, 6 parts of calcined oyster shell, 8 parts of cuttlebone, 5 parts of ginger, 6 parts of sandalwood, 10 parts of salvia miltiorrhiza, 10 parts of calcined oyster shell, 6 parts of immature bitter orange, 7 parts of hearth soil, and 10 parts of clam shell.

[0068] Comparative Example 1:

[0069] The difference from Example 2 lies in the preparation method of the traditional Chinese medicine granules, as detailed below:

[0070] Step 1. Remove impurities from green tangerine peel, dried tangerine peel, peony bark, magnolia bark, fraxinus bark, immature bitter orange, and salvia miltiorrhiza, wash them, dry them at 60℃, pulverize them into coarse powder and pass them through a 20-mesh sieve, mix them, add 10 times the amount of water and decoct twice, 30 minutes each time, filter, combine the filtrates, concentrate to a relative density of 1.10~1.20, add ethanol to make the alcohol content reach 60%, let stand for 24 hours, filter, recover the ethanol, concentrate to a thick paste with a relative density of 1.30~1.35, dry it in an oven at 70℃, pulverize it into extract powder and pass it through an 80-mesh sieve for later use;

[0071] Step 2. Wash the ginger and cut it into 2-3mm thick slices. Crush the sandalwood into coarse powder and pass it through a 20-mesh sieve. Mix the two according to the prescription amount, add 10 times the amount of water, soak for 30 minutes, connect the volatile oil extractor, heat and distill for 6-8 hours, collect the volatile oil, dehydrate it with anhydrous sodium sulfate, dissolve the volatile oil in ethanol, slowly add it dropwise to 8 times the amount of β-CD saturated aqueous solution, stir at 50℃ for 2 hours, refrigerate for 24 hours, filter, dry, pulverize and pass through an 80-mesh sieve to make the inclusion complex powder for later use.

[0072] Step 3. Calcinate oyster shells, oyster shells, and clam shells at 200℃ for 30 minutes until they are red-hot. Immediately quench them in a 40% concentration of rice vinegar solution (50% of the weight of the medicinal materials). Remove them, dry them, and pulverize them through a 100-mesh sieve for later use.

[0073] After the cuttlebone is washed and dried, it is directly crushed and passed through a 100-mesh sieve to retain the activity of calcium carbonate, and then set aside.

[0074] Sieve the hearth soil through a 100-mesh sieve to remove sand and gravel impurities, then stir-fry it in a pan over low heat until slightly charred to enhance its adsorption properties. Set aside.

[0075] Step 4. Mix the extract powder of green tangerine peel from Step 1 with the ginger and sandalwood inclusion compound powder from Step 2, spray with 15% of the total amount of the main drug in 8% ethanol to moisten, and at the same time add calcined oyster shell, cuttlebone, clam shell, calcined oyster shell, and hearth soil powder. Add 50% of the main drug weight of starch and dextrin in a 1:1 ratio (starch and dextrin are added in a 1:1 ratio), mix until the material is uniform and loose, and dry granulate to obtain the final product.

[0076] The method of using the traditional Chinese medicine granules for treating reflux esophagitis of the liver-stomach disharmony type in this embodiment is as follows: 1 bag each time (1 bag is 10g), 2 times / day, 7 days is 1 course of treatment, and 1 to 6 courses of treatment are used.

[0077] It should be noted that the traditional Chinese medicine composition provided in this embodiment can be adjusted according to the severity of the patient's symptoms and the duration of the illness during clinical use. For example, for patients with severe liver and stomach heat stagnation, the dosage of peony bark and fraxinus bark can be increased to 12 parts, and the dosage of clam shell can be increased to 15 parts; for patients with mild spleen and stomach deficiency and cold, the dosage of ginger can be reduced to 3 parts; for patients with qi stagnation and blood stasis syndrome, the dosage of salvia miltiorrhiza can be increased to 15 parts, and the dosage of sandalwood can be increased to 10 parts. Of course, the dosage of each raw material in the above traditional Chinese medicine composition must be controlled within the following range, regardless of any adjustments:

[0078] Green tangerine peel 6-12, dried tangerine peel 6-12, peony bark 6-12, magnolia bark 5-10, fraxinus bark 6-12, calcined oyster shell 5-10, cuttlebone 5-10, fresh ginger 3-9, sandalwood 5-10, salvia miltiorrhiza 8-15, calcined oyster shell 8-15, immature bitter orange 5-10, hearth soil 5-9, clam shell 8-15.

[0079] The traditional Chinese medicine composition provided in this embodiment uses green tangerine peel, immature bitter orange, calcined oyster shell, and cuttlebone as the principal herbs; tangerine peel, magnolia bark, calcined oyster shell, clam shell, sandalwood, peony bark, and fraxinus bark as the assistant herbs; and salvia miltiorrhiza, calcined clay, and ginger as adjuvant herbs. Ginger, due to its warming and stomach-harmonizing properties, guides the medicinal effects to the spleen and stomach in the middle jiao, and also serves as a guide for the medicine to the meridians. The entire formula works by soothing the liver and relieving stagnation, regulating qi and harmonizing the stomach to regulate the fundamental qi mechanism, reducing reflux and neutralizing acid to treat the symptoms of reflux, and is supplemented by clearing heat and removing blood stasis to eliminate the transformation of stagnant heat and blood stasis. At the same time, it also takes into account warming the middle jiao and harmonizing the stomach, and protecting the mucosa. The formula is rigorous, layered, and highly targeted, reflecting the TCM ideas of "differentiation of syndromes and treatment" and "treating both the root cause and the symptoms." This formula has been used for many years at the Third Affiliated Hospital of Changchun University of Traditional Chinese Medicine and Ying's TCM Clinic, and has shown good therapeutic effects on patients with reflux esophagitis of the liver-stomach disharmony type. The following clinical data illustrates the therapeutic effects of the herbal composition of the present invention. Patients with reflux esophagitis of the liver-stomach disharmony type were treated with the herbal granules prepared in Examples 2 and 3, respectively, and are designated as Herbal Granules of Example 2 and Herbal Granules of Example 3. Specific details are as follows:

[0080] 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. Clinical symptoms included acid reflux, heartburn, and chest pain. According to the "Consensus Opinion on the Diagnosis and Treatment of Gastroesophageal Reflux Disease with Traditional Chinese Medicine (2017)", the main symptoms of liver-stomach disharmony type are "heartburn or reflux, epigastric distension and pain, frequent belching, which worsens with emotional distress, and are diagnosed as liver-stomach disharmony type in traditional Chinese medicine." These patients also met the Western medicine diagnosis of reflux esophagitis and had esophageal mucosal damage (confirmed by electronic gastroscopy). According to the Los Angeles classification of reflux esophagitis (RE), RE can be divided into four grades: A, B, C, and D. The classification criteria are as follows: Grade A: damage to one or more esophageal mucosa, with a damage length ≤ 5 mm; Grade B: damage to one or more esophageal mucosa, with a damage length > 5 mm. Grade A refers to mucosal lesions without fusion; Grade B refers to at least two esophageal mucosal lesions that have fused together, with the fusion area less than 75% of the total esophageal circumference; Grade C refers to mucosal lesions that have fused together, with the fusion area greater than or equal to 75% of the total esophageal circumference, a course of disease greater than or equal to 3 months, and no use of acid-suppressing drugs, gastric mucosal protectants, or other medications that affect efficacy in the past 2 weeks. Patients with serious organic diseases, pregnant or lactating women, those allergic to ethanol or Chinese medicine components, and those diagnosed with other syndrome types according to Chinese medicine were excluded. They were randomly divided into 4 groups of 80 patients each for clinical observation.

[0081] 2. Treatment methods:

[0082] Three groups of patients with reflux esophagitis were selected to use the traditional Chinese medicine granules of Example 2, Example 3, and Comparative Example 1, respectively. The dosage was 1 sachet (10g / sachet) twice a day for 7 days as one course of treatment, and 4 courses of treatment were used. The remaining control group used omeprazole enteric-coated capsules (Liweike), produced by Yuekang Pharmaceutical Group Co., Ltd., with a specification of 20 mg / capsule, 2 capsules twice a day, in combination with Zuojin Pills, produced by Hubei Ruihua Pharmaceutical Co., Ltd., with a specification of 18g / bottle / box, 3g twice a day, for 7 days as one course of treatment, and 4 courses of treatment were used.

[0083] 3. Evaluation of therapeutic effect:

[0084] The efficacy evaluation of syndromes is recommended in accordance with the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial Implementation)" and is calculated using the nimodipine method: Efficacy Index = [(Pre-treatment score - Post-treatment score) / Pre-treatment score] × 100%, and is divided into four levels: clinical cure, significant effect, effective, and ineffective.

[0085] 1) Clinical cure: The main symptoms and signs have disappeared or basically disappeared, and the efficacy index is ≥95%;

[0086] 2) Significantly effective: Major symptoms and signs show significant improvement, with 70% ≤ efficacy index < 95%;

[0087] 3) Effective: Major symptoms and signs show significant improvement, with 30% ≤ efficacy index < 70%;

[0088] 4) Ineffective: The main symptoms and signs do not improve significantly, or even worsen, and the efficacy index is <30%.

[0089] 4. Treatment Results

[0090] Table 1: Treatment outcomes of patients with reflux esophagitis using traditional Chinese medicine granules and a control sample (omeprazole)

[0091] Total number of patients / cases Cured / case Significant effect / example Valid / Example Invalid / Example efficiency Control sample (omeprazole combined with Zuojin Pill) 80 22 18 17 23 71.25% Example 2: Traditional Chinese Medicine Granules 80 32 25 19 4 95.00% Example 3: Traditional Chinese Medicine Granules 80 30 26 18 6 92.50% Comparative Example 1: Traditional Chinese Medicine Granules 80 26 21 20 13 83.75%

[0092] The above results show that the efficacy of the traditional Chinese medicine granules used in this invention is significantly higher than that of the control sample group; and the traditional Chinese medicine granules of Example 2 and Example 3 of this invention have better therapeutic effects on patients with liver-stomach disharmony type reflux esophagitis than the traditional Chinese medicine granules of Comparative Example 1. The improvement of the granule preparation process has improved the bioavailability of the drug, thereby achieving better therapeutic effects.

[0093] In addition, this invention also separately investigated the repair effect of traditional Chinese medicine granules on damaged esophageal mucosa, as shown in Table 2:

[0094] Table 2: Endoscopic findings of patients with reflux esophagitis using the traditional Chinese medicine granules from Example 2 and the control sample.

[0095]

[0096] The above results show that the traditional Chinese medicine granules provided by this invention have a good repair effect on damaged esophageal mucosa, especially for grade A and B reflux esophagitis. In the control group, the number of cured + significantly effective + effective cases was 44, with a total effective rate of 44 / 60 × 100% = 73.3%; in the treatment group (traditional Chinese medicine granules of Example 2), the number of cured + significantly effective + effective cases was 55, with a total effective rate of 55 / 60 × 100% = 91.7%. Therefore, this invention has a higher total effective rate and more significant effect on patients with grade A and B reflux esophagitis. Furthermore... This invention also shows good therapeutic effects on patients with grade C and D reflux esophagitis. In the control group, the number of cured, significantly effective, and effective cases was 10, with a total effective rate of 10 / 20 × 100% = 50%. In the treatment group, the number of cured, significantly effective, and effective cases was 17, with a total effective rate of 17 / 20 × 100% = 85%, which is significantly better than the control group. The good repair effect can restore the esophageal mucosa to its normal barrier function, effectively blocking the erosion of refluxed substances such as gastric acid and pepsin, reducing the possibility of the esophagus being damaged again, thereby reducing the recurrence rate of reflux esophagitis.

[0097] The traditional Chinese medicine granules provided by this invention determine the course of treatment based on the patient's condition, typically requiring 1 to 6 courses. These granules demonstrate consistently good therapeutic effects for patients with different grades of reflux esophagitis, and recurrence is less likely after treatment. Typical case examples illustrate this below:

[0098] (1) Mr. Li, born in 1982, is from Shenyang City, Liaoning Province. He is a sales manager and visited Ying's Traditional Chinese Medicine Clinic in Nanguan District, Changchun City in May 2023. For the past two years, the patient has experienced recurrent acid reflux and heartburn, especially after meals and when emotionally stressed. He also experienced abdominal distension, frequent belching, and occasional distending sensation in the hypochondriac region. He usually experiences high work pressure and is easily irritable. His tongue is reddish with a thin white-yellow coating and a wiry pulse. He was diagnosed with reflux esophagitis by examination, and an electronic gastroscopy confirmed that his RE grade was A. Traditional Chinese Medicine diagnosis: Liver-stomach disharmony syndrome. He was given the Chinese medicine granules of Example 2 of this invention orally, 10g each time, twice a day. After 2 weeks of treatment, the frequency of acid reflux and heartburn decreased, and the belching and hypochondriac distension decreased. He continued treatment until the 6th week, when the abdominal distension basically disappeared, and acid reflux and heartburn only occurred occasionally when he was careless with his diet or when he was extremely anxious. Follow-up until July 2024 showed that the condition was stable and there was no significant recurrence. Electronic gastroscopy showed no mucosal damage.

[0099] (2) Ms. Zhang, born in 1975, is from Harbin, Heilongjiang Province, and is a middle school teacher. She visited Ying's Traditional Chinese Medicine Clinic in Nanguan District, Changchun City in September 2022. One and a half years ago, after an argument over trivial family matters, she began to experience burning pain behind the sternum, acid reflux, and a foreign body sensation in her throat. These symptoms were often triggered or aggravated by emotional fluctuations or eating too much. She also had a poor appetite, frequent sighing, a pale red tongue with a thin white coating, and a wiry and thready pulse. After examination, she was diagnosed with reflux esophagitis, and an electronic gastroscopy confirmed that her RE grade was B. Traditional Chinese Medicine diagnosis: Liver-Stomach Disharmony Syndrome. The patient took 10g of the Chinese herbal granules from Example 2 of this invention orally, twice a day. After 3 weeks of treatment, the burning pain behind the sternum was reduced, the frequency of acid reflux decreased, the foreign body sensation in the throat and belching improved, and the mood was slightly better. After 5 courses of treatment, the main symptoms basically disappeared and the appetite was restored. During the follow-up until March 2024, the patient occasionally experienced mild acid reflux due to fatigue or anger, but the degree was mild and the duration was short, and it did not affect the life. The electronic gastroscopy examination was grade A.

[0100] (3) Mr. Chen, born in 1968, is from Jilin City, Jilin Province, and is a self-employed individual. He visited Ying's Traditional Chinese Medicine Clinic in Nanguan District, Changchun City in January 2024. Three years ago, the patient began experiencing acid reflux and heartburn after meals and at night, accompanied by discomfort in the epigastric region and occasional bloating and pain radiating to both hypochondria. He is usually irritable and often gets angry over trivial matters. He had previously taken Western antacids, which were effective initially, but the symptoms easily recurred after stopping the medication. His tongue was slightly red with a thin yellow coating, and his pulse was wiry and rapid. He was diagnosed with reflux esophagitis after examination, and an electronic gastroscopy confirmed that his RE grade was B. Traditional Chinese Medicine diagnosis: Liver-Stomach Disharmony Syndrome. The herbal granules of Example 2 of this invention were administered orally, 10g each time, twice a day. After 2 weeks of treatment, acid reflux, heartburn, and a feeling of discomfort were reduced, rib pain was relieved, and mood was slightly stable. After 4 courses of treatment, nocturnal reflux was basically controlled, and stomach discomfort was significantly reduced. After a total of 6 courses of treatment, clinical symptoms disappeared, and mood was stable. Follow-up until May 2025 showed no recurrence, and electronic gastroscopy showed no damage.

[0101] (4) Ms. Liu, born in 1990, is a designer from Hohhot, Inner Mongolia Autonomous Region. She visited Ying's Traditional Chinese Medicine Clinic in Nanguan District, Changchun in July 2023. Six months postpartum, the patient began experiencing frequent belching, acid reflux, a feeling of blockage in the throat, and significant abdominal distension after eating due to anxiety about childbirth; accompanied by breast tenderness and poor sleep; her tongue was pale red with a thin white coating, and her pulse was wiry and thready; she was diagnosed with reflux esophagitis after examination. Traditional Chinese Medicine diagnosis: Liver-stomach disharmony syndrome. She took the Chinese medicine granules of Example 2 of this invention orally, 10g each time, twice a day; after one week of treatment, belching and abdominal distension were significantly reduced, acid reflux decreased, sleep improved, and breast tenderness was relieved; after one month of treatment, the feeling of blockage in the throat disappeared, her mood improved, and the main symptoms were basically controlled; she was followed up until December 2024, and her condition was stable, with occasional mild belching and no other discomfort.

[0102] (5) Mr. Zhao, born in 1955, is from Dalian City, Liaoning Province, and is retired. He visited Ying's Traditional Chinese Medicine Clinic in Nanguan District, Changchun City in November 2022. For the past four years, the patient has experienced recurrent acid reflux, heartburn, and retrosternal pain, which is often aggravated by arguments with his children or excessive worry. He also experiences epigastric discomfort, poor appetite, and fatigue. He has a history of hypertension, which is well controlled. His tongue is pale with teeth marks on the edges, and the coating is thin and white. His pulse is wiry, thready, and weak. He was diagnosed with reflux esophagitis, and an electronic gastroscopy confirmed that his RE grade was C. Traditional Chinese Medicine diagnosis: Liver-Stomach Disharmony Syndrome. He was given the Chinese medicine granules of Example 2 of this invention orally, 10g each time, twice a day. After 10 days of treatment, the frequency of acid reflux and heartburn decreased, chest pain lessened, appetite improved slightly, and his mental state improved. After three courses of treatment, epigastric discomfort and fatigue were significantly relieved. After five courses of treatment, the clinical symptoms basically disappeared, the patient's mood stabilized, and physical strength recovered. Follow-up until October 2024 showed that the condition was stable, with no recurrence, and the electronic gastroscopy examination was grade A.

[0103] 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 within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating reflux esophagitis of the liver-stomach disharmony type, characterized in that, The traditional Chinese medicine composition consists of the following raw materials in parts by weight: 6-12 parts green tangerine peel, 6-12 parts dried tangerine peel, 6-12 parts peony bark, 5-10 parts magnolia bark, 6-12 parts fraxinus bark, 5-10 parts calcined oyster shell, 5-10 parts cuttlebone, 3-9 parts fresh ginger, 5-10 parts sandalwood, 8-15 parts salvia miltiorrhiza, 8-15 parts calcined oyster shell, 5-10 parts immature bitter orange, 5-9 parts hearth soil, and 8-15 parts clam shell.

2. The traditional Chinese medicine composition for treating reflux esophagitis of the liver-stomach disharmony type according to claim 1, characterized in that, The traditional Chinese medicine composition consists of the following raw materials in parts by weight: 6-12 parts green tangerine peel, 10-12 parts dried tangerine peel, 8-12 parts peony bark, 7-10 parts magnolia bark, 10-12 parts fraxinus bark, 6-10 parts calcined oyster shell, 8-10 parts cuttlebone, 5-9 parts fresh ginger, 6-10 parts sandalwood, 10-15 parts salvia miltiorrhiza, 10-15 parts calcined oyster shell, 6-10 parts immature bitter orange, 7-9 parts hearth soil, and 10-15 parts clam shell.

3. The traditional Chinese medicine composition for treating reflux esophagitis of the liver-stomach disharmony type according to claim 2, characterized in that, The traditional Chinese medicine composition consists of the following raw materials in parts by weight: 10-12 parts green tangerine peel, 10-12 parts dried tangerine peel, 8-10 parts peony bark, 7-8 parts magnolia bark, 10-12 parts fraxinus bark, 8-10 parts calcined oyster shell, 8-10 parts cuttlebone, 8-9 parts fresh ginger, 8-10 parts sandalwood, 10-15 parts salvia miltiorrhiza, 12-15 parts calcined oyster shell, 6-10 parts immature bitter orange, 8-9 parts hearth soil, and 12-15 parts clam shell.

4. The traditional Chinese medicine composition for treating reflux esophagitis of the liver-stomach disharmony type as described in any one of claims 1 to 3 is used in the preparation of a medicament for treating reflux esophagitis of the liver-stomach disharmony type.

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

6. A traditional Chinese medicine granule for treating reflux esophagitis due to liver-stomach disharmony, characterized in that, The herbal granules comprise the following raw materials by weight: 6-12g of green tangerine peel, 6-12g of dried tangerine peel, 6-12g of peony bark, 5-10g of magnolia bark, 6-12g of fraxinus bark, 5-10g of calcined oyster shell, 5-10g of cuttlebone, 3-9g of ginger, 5-10g of sandalwood, 8-15g of salvia miltiorrhiza, 8-15g of calcined oyster shell, 5-10g of immature bitter orange, 5-9g of hearth soil, and 8-15g of clam shell; The preparation method of the traditional Chinese medicine granules includes the following steps: Step 1. Process green tangerine peel and dried tangerine peel together, mix and grind into coarse powder, sieve, mix coarse powder with enzyme solution for enzymatic hydrolysis, then add water and decoct, press and filter to extract juice, dry, grind, sieve, and obtain dry extract powder for later use. Step 2. Slice the bark of Qinpi and the bark of Mudanpi, soak them, extract them at 80℃, filter them while keeping them warm, concentrate them under reduced pressure, freeze the resulting extract to form a brittle solid, pulverize them with airflow to obtain a dry extract powder for later use. Step 3. Crush Magnolia officinalis into coarse powder and sieve; crush Citrus aurantium into powder; mix the two together and add 50% ethanol for ultrasonic-microwave co-extraction at room temperature; slice Salvia miltiorrhiza, add 50% ethanol for ultrasonic-microwave co-extraction at 60℃, cool and filter finely, combine with the extract of Magnolia officinalis and Citrus aurantium, concentrate under reduced pressure, add microcrystalline cellulose, spray dry to obtain powder for later use; Step 4. Calcined corrugated iron was quenched with 20% rice vinegar, dried by forced air, pulverized by air jet milling, and ball milled to 300-500 nm. Calcined oyster shell was quenched with 20% rice vinegar until brittle, dried by forced air, pulverized by air jet milling, separated by a classifier wheel, and passed through a 325-mesh sieve for later use. Cuttlebone was boiled in 2% NaOH solution at 80℃ for 1 hour, washed with water until neutral, soaked in 5% acetic acid for 1 hour, washed with water until pH 6.5-7.0, dried by forced air, and pulverized by air jet milling to D50=5μm. Clam shells were softened and calcined at 150℃, added to 20% rice vinegar, stirred until no bubbles were observed, filtered, passed through a 200-mesh sieve, added to PVP-K30 aqueous solution, stirred in a water bath at 60℃, vacuum filtered, and ball milled to D90≤400nm. Hearth soil was boiled in 10% hydrochloric acid, washed with water until pH 6.0, calcined at 750℃ for 4 hours, and pulverized by air jet milling to D90≤2μm. The above five ultrafine powders were mixed and set aside. Step 5. Slice ginger, extract with supercritical CO2, and collect ginger volatile oil; crush sandalwood into coarse powder, sieve, extract with supercritical CO2, and collect sandalwood volatile oil; combine ginger volatile oil and sandalwood volatile oil, then incorporate them at an oil:β-cyclodextrin ratio of 1:6, stir, and spray dry to obtain incorporation powder; Step 6. Mix the powders obtained in Steps 1, 2, 3 and 5, wet with 8% ethanol, add the mixed powder obtained in Step 4, add starch and dextrin, mix well, roll and dry to form granules.

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

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

9. A traditional Chinese medicine granule for treating reflux esophagitis of the liver-stomach disharmony type according to claim 6, characterized in that, In step 5, the ginger slices are extracted using supercritical CO2 at 35°C and 20MPa; the sandalwood is crushed into coarse powder, passed through a 20-mesh sieve, and then extracted using supercritical CO2 at 40°C and 25MPa.

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

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