Traditional Chinese medicine composition for treating stomachache caused by liver-qi attacking stomach and preparation method of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicine compositions, in particular to a traditional Chinese medicine composition for treating stomachache caused by liver-qi attacking stomach and a preparation method thereof, and the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 8-12 parts of radix bupleuri, 12-18 parts of radix paeoniae alba, 10-15 parts of bighead atractylodes rhizome, 12-18 parts of poria cocos, 10-15 parts of angelica sinensis, 3-6 parts of mint, 6-10 parts of turmeric, 10-15 parts of corydalis tuber, 4-6 parts of liquorice, 8-12 parts of fingered citron, 8-12 parts of rhizoma cyperi, 8-12 parts of rhizoma bletillae and 15-25 parts of cuttlebone. The traditional Chinese medicine composition has the effects of soothing the liver, regulating qi, harmonizing the stomach, calming adverse-rising energy, relieving hyperacidity and relieving pain through the combination of the medicines, so that the liver qi is smooth, the stomach qi is reduced, the qi and blood are smooth, and no pain is caused if the qi and blood are smooth.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, and in particular to a traditional Chinese medicine composition for treating stomach pain caused by liver qi invading the stomach and its preparation method. Background Technology

[0002] Stomach pain due to liver qi invading the stomach is a very common syndrome type in traditional Chinese medicine (TCM) clinical diagnosis and treatment. It mainly refers to a type of stomach pain caused by liver qi stagnation due to emotional imbalance, which then invades the stomach. Its core pathogenesis lies in the dysfunction of the liver's function of regulating qi flow: when the body is in a state of prolonged emotional fluctuation such as anger, depression, or excessive thinking, it is most likely to lead to stagnation of liver qi. Since the liver meridian runs along the hypochondria and borders the stomach, stagnant liver qi easily invades the stomach, causing stagnation of stomach qi and impaired descending function. This results in a series of symptoms, typically manifested as distending pain in the stomach radiating to the hypochondria, stabbing pain, frequent belching, and pain that worsens with emotional fluctuations. Based on the holistic view of "seeing liver disease, one knows that the liver transmits to the spleen," TCM has always emphasized that this type of syndrome requires diagnosis and treatment based on the physiological and pathological relationship between the liver and stomach. In clinical practice, the treatment of this syndrome is based on the principle of addressing the root cause by soothing the liver, regulating qi, and relieving depression, while simultaneously addressing the symptoms by harmonizing the stomach, relieving nausea, and alleviating pain. Classic formulas such as Chaihu Shugan San and Xiaoyao San remain important bases for modifications. With the accelerated pace of modern life and increased social pressure, the incidence of gastrointestinal diseases caused by emotional factors is showing a significant upward trend.

[0003] However, current techniques often rely heavily on piling up liver-soothing and qi-regulating herbs. While modifications based on classic formulas like Chaihu Shugan San or Xiaoyao San are effective, many formulas excessively depend on aromatic and drying qi-regulating herbs such as Xiangfu, Muxiang, and Chenpi. Although these herbs can quickly relieve qi stagnation, prolonged use or improper combinations can easily deplete liver yin and stomach fluids. For patients with a long course of illness and mixed deficiency and excess (i.e., prolonged qi stagnation accompanied by yin deficiency), simply using aromatic and drying herbs to regulate qi often aggravates yin deficiency symptoms such as dry mouth, constipation, or stomach upset, leading to a prolonged and difficult-to-cure condition. In clinical practice, liver qi stagnation not only attacks the stomach but also easily transforms into fire (liver and stomach heat stagnation) or obstructs blood circulation (qi stagnation and blood stasis). Many conventional prescriptions contain heat-clearing drugs, but lack in-depth consideration of "releasing stagnant heat," making it difficult for the stagnant heat to dissipate. At the same time, the timing and dosage of blood-activating drugs are also relatively vague. For patients with long-term qi stagnation and stomach meridian obstruction, the effect is often slow and it is difficult to relieve pain quickly. Summary of the Invention

[0004] In order to solve the problems mentioned in the background art, the present invention provides a traditional Chinese medicine composition for treating stomach pain of the liver qi invading the stomach type and its preparation method.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides a traditional Chinese medicine composition for treating stomach pain caused by liver qi invading the stomach. The composition is made from specific weight parts of raw materials, and the weight parts range of each raw material are as follows: Bupleurum chinense 8-12 parts, Paeonia lactiflora 12-18 parts, Atractylodes macrocephala 10-15 parts, Poria cocos 12-18 parts, Angelica sinensis 10-15 parts, Mentha haplocalyx 3-6 parts, Curcuma longa 6-10 parts, Corydalis yanhusuo 10-15 parts, Glycyrrhiza uralensis 4-6 parts, Citrus medica 8-12 parts, Cyperus rotundus 8-12 parts, Bletilla striata 8-12 parts, and Sepia esculenta 15-25 parts.

[0006] The above-mentioned raw materials are all Chinese medicinal materials that meet the standards of Part I of the Pharmacopoeia of the People's Republic of China. Among them, Bupleurum is the dried root of Bupleurum chinense or Bupleurum stenoptera, which are plants of the genus Bupleurum in the family Apiaceae; Paeonia lactiflora is the dried root of Paeonia suffruticosa, which is plant of the genus Paeonia in the family Ranunculaceae, which is processed; and Atractylodes macrocephala is the dried rhizome of Atractylodes macrocephala, which is plant of the genus Atractylodes in the family Asteraceae.

[0007] As a preferred embodiment of the traditional Chinese medicine composition of the present invention, the specific weight parts of each raw material are as follows: Bupleurum chinense 10 parts, Paeonia lactiflora 15 parts, Atractylodes macrocephala 12 parts, Poria cocos 15 parts, Angelica sinensis 12 parts, Mentha haplocalyx 5 parts, Curcuma longa 8 parts, Corydalis yanhusuo 12 parts, Glycyrrhiza uralensis 5 parts, Citrus medica 10 parts, Bletilla striata 10 parts, Cyperus rotundus 10 parts, and Cuttlebone 20 parts.

[0008] Furthermore, the licorice in the above-mentioned traditional Chinese medicine composition is roasted licorice, which is made by mixing licorice slices with honey, stir-frying until the surface is dark yellow and slightly shiny, and no longer sticky, and then removing it and letting it cool. The amount of honey used is 20 to 30 parts by weight of licorice.

[0009] This invention also provides a method for preparing the above-mentioned traditional Chinese medicine composition, the method comprising the following steps: (1) Weigh each raw material according to the above ratio and soak it in water; wherein, the amount of water added is 5 to 8 times the total weight of the raw materials, the soaking temperature is 20 to 30°C, the soaking time is 20 to 40 minutes, preferably 30 minutes, and the water is stirred once every 10 minutes during the soaking process.

[0010] (2) Boil the soaked raw materials over high heat, then simmer over low heat, and filter the liquid. The high heat is 100-110℃ and the boiling time is 5-10 minutes. The simmering time is 25-35 minutes, preferably 30 minutes. During the simmering process, keep the liquid at a gentle boil to avoid overflow. When filtering the liquid, use a 100-120 mesh filter.

[0011] (3) Add water to the dregs and decoct again, then combine the two decoctions to obtain the final product; the amount of water added during the second decoction is 3 to 5 times the weight of the dregs, and the second decoction is carried out over a low flame for 20 to 30 minutes. The combined decoction can be concentrated under reduced pressure to a relative density of 1.05 to 1.10 (25°C).

[0012] The traditional Chinese medicine composition of the present invention can be prepared into various dosage forms, specifically including decoctions, powders, pills, capsules, or granules. Specifically, decoctions are prepared by directly dispensing the combined medicinal liquids; powders are prepared by pulverizing each raw material, passing it through an 80-100 mesh sieve, and then mixing them evenly; pills are prepared by adding refined honey or water to the powder to form pills, with a pill weight of 0.5-1g / pill; capsules are prepared by filling the powder into empty capsules, with each capsule containing 0.3-0.5g; and granules are prepared by concentrating and drying the combined medicinal liquids to form granules with a particle size of 10-20 mesh.

[0013] For powders, pills, capsules, or granules, the dosage per administration is 8-12 grams based on the amount of raw medicinal material, administered 2-3 times daily. For powders, the dosage is 2-3 grams per administration; for pills, the dosage is 6-9 grams per administration; for capsules, the dosage is 2-3 capsules per administration; and for granules, the dosage is 1 packet per administration (each packet contains 8-12 grams of raw medicinal material).

[0014] The traditional Chinese medicine composition of the present invention can be used to prepare a drug for treating stomach pain of the liver qi invading the stomach type. The drug can be used alone or in combination with conventional Western medicine for treating stomach pain of the liver qi invading the stomach type. When used in combination, the dosage of Western medicine can be reduced.

[0015] In the above application, the stomach pain caused by liver qi invading the stomach includes one or more of the following symptoms: epigastric distension and pain, pain radiating to the hypochondria, belching, acid reflux, irritability, frequent sighing, chest tightness during menstruation, and excessive menstruation. These symptoms meet the diagnostic criteria for stomach pain caused by liver qi invading the stomach in the "Standards for Diagnosis and Efficacy of Traditional Chinese Medicine Diseases". Among them, epigastric distension and pain radiating to the hypochondria are typical symptoms, while the others are accompanying symptoms.

[0016] The beneficial effects of this invention are: 1. Principal Herbs (Core): Bupleurum: Soothes the liver and relieves depression, regulates Qi, and is the main herb for treating liver stagnation. Cyperus: Regulates Qi, relieves depression, and alleviates pain, specifically soothes stagnation of liver and stomach Qi.

[0017] Assistant herbs (supporting the main treatment): White peony root: nourishes blood and softens the liver, relieves spasms and pain, prevents excessive pungent and dispersing herbs from damaging yin. Angelica sinensis: nourishes blood and invigorates blood circulation, replenishes the liver's essence to assist its function. Corydalis yanhusuo: promotes qi and invigorates blood circulation, effectively relieves pain. Buddha's hand: soothes the liver and regulates qi, strengthens the spleen and stomach, promotes qi circulation and relieves pain.

[0018] Adjuvant herbs (for both treatment, antacids, stomach protection, and blood circulation): Atractylodes macrocephala: strengthens the spleen and replenishes qi, supports earth element and suppresses wood element, prevents liver wood from overacting on the spleen. Poria cocos: sweet, bland, neutral, enters the heart, spleen, and kidney meridians, promotes diuresis and eliminates dampness, strengthens the spleen, and expels dampness from the spleen and stomach through urination. Mentha haplocalyx: lightly clears and soothes the liver, disperses stagnant heat. Curcuma longa: invigorates blood and qi, unblocks meridians and relieves pain. Bletilla striata: astringent and hemostatic, protects the gastric mucosa. Cuttlebone: antacid, relieves pain, astringent and protective of the gastric mucosa.

[0019] Adjuvant (harmonizing): Prepared licorice root: tonifies qi and strengthens the middle jiao, relieves spasms and pain, harmonizes the effects of other herbs. Usage (standard) 2. From the perspective of modern pharmacology, this composition exerts its therapeutic effect through synergistic action at multiple targets and via multiple pathways. The specific mechanism is as follows: The saikosaponins in Bupleurum, the volatile oils in Cyperus rotundus, and the limonene in Citrus reticulata can bidirectionally regulate the function of gastrointestinal smooth muscle. They can relieve gastrointestinal smooth muscle spasms, reduce symptoms such as epigastric distension and pain radiating to the hypochondria, and promote gastrointestinal motility, improve discomfort such as epigastric fullness and belching caused by qi stagnation, and restore normal gastrointestinal motility. Paeoniflorin in Paeonia lactiflora and corydalis yanhusuo have significant analgesic and anti-inflammatory activities. They can reduce the hypersensitivity of gastrointestinal viscera by inhibiting the release of inflammatory mediators such as prostaglandins and interleukins, thereby relieving stomach pain from the root and reducing gastric mucosal inflammation.

[0020] The calcium carbonate and calcium phosphate in cuttlebone can neutralize excess stomach acid and relieve symptoms such as acid reflux, heartburn, and other discomforts. The gum in Bletilla striata can form a protective film on the gastric mucosa, reducing the stimulation of the gastric mucosa by stomach acid and pepsin, promoting the repair of damaged gastric mucosa, enhancing the gastric mucosal barrier function, and preventing recurrent stomach pain. Curcumin in turmeric and ferulic acid in angelica can improve gastrointestinal blood circulation and promote blood circulation, which can relieve gastrointestinal mucosal microcirculation disorders, reduce blood stasis, and promote the resolution of inflammation.

[0021] Bupleurum, white peony root, and peppermint, among other liver-soothing and mood-regulating herbs, can regulate the hypothalamic-pituitary-adrenal axis, affecting the secretion of monoamine neurotransmitters such as serotonin and dopamine, thus exerting anti-anxiety and antidepressant effects. They can also block the impact of emotional fluctuations on gastrointestinal function, preventing and alleviating the onset of stomach pain caused by liver qi invading the stomach from the root cause. The polysaccharide components in Atractylodes macrocephala and Poria cocos can regulate the balance of intestinal flora, enhance the spleen and stomach's digestive function, improve the body's immunity, and reduce the risk of recurrence of gastrointestinal diseases. The diammonium glycyrrhizate in prepared licorice root has anti-inflammatory and gastric mucosal protective effects, while also enhancing the analgesic effect of the entire formula, harmonizing the effects of various drug components, and improving the overall therapeutic efficacy. Detailed Implementation

[0022] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0023] Example 1 This embodiment provides a traditional Chinese medicine composition for treating stomach pain caused by liver qi invading the stomach. The raw materials are weighed in the following proportions: Bupleurum chinense 8 parts, Paeonia lactiflora 12 parts, Atractylodes macrocephala 10 parts, Poria cocos 12 parts, Angelica sinensis 10 parts, Mentha haplocalyx 3 parts, Curcuma longa 6 parts, Corydalis yanhusuo 10 parts, Glycyrrhiza uralensis (processed) 4 parts, Citrus medica 8 parts, Cyperus rotundus 8 parts, Bletilla striata 8 parts, and Sepia esculenta 15 parts.

[0024] Preparation method: Weigh each raw material (all conforming to the standards of Part I of the Pharmacopoeia of the People's Republic of China) according to the above proportions, add 5 times the total weight of the raw materials with water, soak at 20℃ for 20 minutes, stirring once every 10 minutes during the soaking process; place the soaked raw materials in a decoction pot, bring to a boil over high heat (100℃) for 5 minutes, then reduce to low heat (keeping the liquid at a gentle boil) and decoct for 25 minutes, filter the liquid through a 100-mesh filter; add 3 times the weight of the dregs with water to the dregs, decoct again over low heat for 20 minutes, filter the liquid, combine the two liquids, concentrate under reduced pressure to a relative density of 1.05 (25℃), prepare a decoction, and package it.

[0025] This decoction is taken in doses of 200ml (containing 8 grams of raw herbs) twice daily. It can be used to relieve symptoms such as abdominal distension and frequent sighing caused by stomach pain due to liver qi invading the stomach.

[0026] Example 2 This embodiment provides a traditional Chinese medicine composition for treating stomach pain caused by liver qi invading the stomach. The raw materials are weighed in the following proportions: Bupleurum chinense 10 parts, Paeonia lactiflora 15 parts, Atractylodes macrocephala 12 parts, Poria cocos 15 parts, Angelica sinensis 12 parts, Mentha haplocalyx 5 parts, Curcuma longa 8 parts, Corydalis yanhusuo 12 parts, Glycyrrhiza uralensis (processed) 5 parts, Citrus medica 10 parts, Cyperus rotundus 10 parts, Bletilla striata 10 parts, and Cuttlebone 20 parts.

[0027] Preparation method: Weigh each raw material (all conforming to the standards of Part I of the Pharmacopoeia of the People's Republic of China) according to the above proportions, add 6.5 times the total weight of the raw materials with water, soak at 25℃ for 30 minutes, stirring once every 10 minutes during the soaking process; place the soaked raw materials in a decoction pot, bring to a boil over high heat (105℃) for 8 minutes, then reduce to low heat (keeping the liquid at a gentle boil) and decoct for 30 minutes, filter the liquid through a 110-mesh filter; add 4 times the weight of the dregs with water to the dregs, decoct again over low heat for 25 minutes, filter the liquid, combine the two liquids, concentrate under reduced pressure to a relative density of 1.08 (25℃), spray dry to make granules (particle size 15 mesh), and package into bags containing 10 grams of raw materials each.

[0028] This granule is taken 1 sachet each time, 3 times a day, and can be used to relieve various symptoms such as stomach bloating and pain, acid reflux, heartburn, irritability and restlessness caused by liver qi invading the stomach.

[0029] Example 3 This embodiment provides a traditional Chinese medicine composition for treating stomach pain caused by liver qi invading the stomach. The raw materials are weighed in the following proportions: Bupleurum chinense 12 parts, Paeonia lactiflora 18 parts, Atractylodes macrocephala 15 parts, Poria cocos 18 parts, Angelica sinensis 15 parts, Mentha haplocalyx 6 parts, Curcuma longa 10 parts, Corydalis yanhusuo 15 parts, Glycyrrhiza uralensis (processed) 6 parts, Citrus medica 12 parts, Cyperus rotundus 12 parts, Bletilla striata 12 parts, and Cuttlebone 25 parts.

[0030] Preparation method: Weigh each raw material (all conforming to the standards of Part I of the Pharmacopoeia of the People's Republic of China) according to the above proportions, add 8 times the total weight of the raw materials with water, soak at 30℃ for 40 minutes, stirring once every 10 minutes during the soaking process; place the soaked raw materials in a decoction pot, bring to a boil over high heat (110℃) for 10 minutes, then reduce to low heat (keeping the liquid at a gentle boil) and decoct for 35 minutes, filter the liquid through a 120-mesh filter; add 5 times the weight of the dregs with water to the dregs, decoct again over low heat for 30 minutes, filter the liquid, combine the two liquids, concentrate under reduced pressure to a relative density of 1.10 (25℃), dry, pulverize and pass through a 90-mesh sieve to make a powder, which is then obtained.

[0031] This powder is taken at a dose of 2.5g (containing 12g of raw herbs) twice daily. It can be used to relieve symptoms such as abdominal distension and pain, pain radiating to the hypochondria, and chest tightness during menstruation caused by liver qi invading the stomach.

[0032] To evaluate the therapeutic effects of the traditional Chinese medicine compositions and different dosage forms of Examples 1-3 on stomach pain caused by liver qi invading the stomach, the following animal experiments were conducted. All steps followed the relevant ethical guidelines for the use of experimental animals and the requirements of pharmacological experimental methodologies.

[0033] One hundred and twenty SPF-grade SD rats (half male and half female), weighing between 200 ± 20 grams, were purchased from a laboratory animal production center. All rats underwent a seven-day acclimatization period upon arrival at the laboratory. The rearing environment was strictly controlled, with a temperature of 22 ± 2℃, relative humidity of 55 ± 5%, and a circadian rhythm of 12 hours of light and 12 hours of darkness. Rats were housed in separate cages, with no more than five rats per cage, ensuring sufficient space for movement. They were allowed free access to standard maintenance feed and purified water to mitigate the stress caused by transportation and environmental changes.

[0034] After the adaptive feeding period, the model of stomach pain due to liver qi stagnation was established. Except for the pre-defined blank control group, all other rats received combined modeling stimulation. The modeling method used restraint stress combined with anhydrous ethanol gavage. The specific procedure was as follows: From 9:00 AM to 11:00 AM daily, rats were gently placed in a self-made restraint device (which restricted the rats' physical activity without causing harm) for 2 hours to simulate emotional distress and liver qi stagnation. This process was repeated for 14 days. Starting from the 8th day of modeling, every afternoon (one hour after the restraint ended), the modeling rats (including the subsequent model control group, positive control group, and all test drug groups) were administered anhydrous ethanol by gavage at a dose of 0.8 ml per 100 grams of body weight for 7 consecutive days to simulate the direct damage to the gastric mucosa caused by factors such as dietary indiscretion. The blank control group rats were administered an equal volume of purified water during the same period.

[0035] On day 14 of model establishment, the success of the model construction needs to be verified. By observing the overall condition of the model rats, if they exhibit lethargy, huddling together, dry fur, significantly reduced food intake, slow activity, and sluggish response to mild stimuli, 2-3 rats are randomly selected from each group for pre-euthanasia, and gastric tissue is collected for observation. If obvious congestion, edema, or even punctate erosion of the gastric mucosa is visible to the naked eye and under a microscope, and the serum motilin and gastrin levels are significantly lower than those in the control group (statistical analysis P<0.05), then the model is considered to have been successfully established.

[0036] After successful modeling, 100 stable rats were selected from the remaining successfully modeled rats and the blank control group for inclusion in the formal experiment. These 100 rats were randomly divided into 6 groups using a random number table method, ensuring that each group had half males and half females. Specifically, the groups were: blank control group, model control group, positive drug control group, test drug group 1 (decoction group of Example 1), test drug group 2 (granule group of Example 2), and test drug group 3 (capsule group of Example 3), with 20 rats in each group.

[0037] After grouping, the drug administration intervention phase began. All drugs were freshly prepared before administration. Test drug 1 (Decoction of Example 1) was prepared according to the method of Patent Example 1 and finally concentrated to a solution containing 1.38 g of crude drug per milliliter; test drug 2 (Particles of Example 2) was ground into a fine powder and then prepared into a suspension containing 1.29 g of crude drug per milliliter with purified water; test drug 3 (Capsules of Example 3) was prepared by taking the contents and preparing into a suspension containing 1.38 g of crude drug per milliliter with purified water. The positive control drug was commercially available Qizhi Weitong Granules, which were also prepared into a suspension containing 0.5 g of crude drug per milliliter with purified water. The dosage was converted to the equivalent dose for rats based on the body surface area of ​​the adult clinical dosage. Rats in each group were administered the drug by gavage from 14:00 to 15:00 every day, with a uniform gavage volume of 1 ml per 100 g of body weight to ensure uniformity of administration. The blank control group and the model control group were given the same volume of purified water. The rats were given the drug continuously for 7 days. During this period, all rats had free access to food and water. The rats were observed and recorded daily in detail for their mental state, fur color, activity level, food intake, water intake, and defecation. Attention was paid to any abnormal reactions or deaths.

[0038] After the last administration, all rats were fasted for 12 hours but allowed free access to water, followed by sample collection and index testing.

[0039] The first step was behavioral assessment. In a quiet environment, two researchers unfamiliar with the grouping process independently observed and scored each rat. The scoring criteria were based on the "Experimental Methodology of Traditional Chinese Medicine Pharmacology," quantifying the results across four dimensions: 1. Mental state: 0 points for being listless and curled up; 1 point for being in poor spirits and preferring quiet and inactivity; 2 points for being in fair spirits and moving freely; 3 points for being energetic and quick to react.

[0040] 2. Food intake: 0 points for a reduction of more than 60% compared to the control group; 1 point for a reduction of 40%-60%; 2 points for a reduction of 20%-40%; 3 points for being basically the same as or slightly less than the control group.

[0041] 3. Activity level: Almost no activity, lying still is 0 points; significantly reduced activity, occasional walking is 1 point; normal activity, free exploration is 2 points; active and frequent climbing is 3 points.

[0042] 4. Stimulus response: No response to light touch or sound is 0 points; sluggish response and slow avoidance is 1 point; normal response and rapid avoidance is 2 points; sensitive response and strong avoidance is 3 points. Add up the scores of the four items. The higher the total score, the better the overall condition of the rat and the milder the stomach pain symptoms.

[0043] After behavioral assessment, serum samples were collected. Approximately 5 ml of whole blood was collected from each rat using the orbital venous plexus method and placed in a standard centrifuge tube without anticoagulant. After allowing the blood to clot naturally at room temperature for 30 minutes, the tubes were centrifuged at 3000 rpm for 15 minutes. The supernatant pale yellow serum was carefully aspirated, aliquoted into sterile EP tubes, labeled, and stored at -20°C for subsequent standardized testing.

[0044] Serum markers were detected using enzyme-linked immunosorbent assay (ELISA). The specific procedures were strictly followed according to the instructions of each kit. Before testing, serum samples and kits were equilibrated to room temperature. Standard and sample wells were prepared, and different concentrations of standards or test serum were added sequentially. Then, biotin-labeled anti-rat motilin, gastrin, serotonin, or tumor necrosis factor-α antibody was added. The plate was sealed and incubated at 37°C for 60 minutes. After incubation, the liquid was discarded, the plate was dried, and each well was filled with washing buffer. After standing for 30 seconds, the buffer was discarded. This washing process was repeated 5 times, and the wells were then patted dry. Except for the blank wells, horseradish peroxidase-labeled streptavidin working solution was added to each well, and the plate was incubated at 37°C for 30 minutes. After washing 5 more times, substrate solution (e.g., TMB) was added to each well, and the plate was incubated at 37°C for 15 minutes in the dark. Finally, stop solution was added, and the absorbance of each well was measured at 450 nm using a microplate reader. A standard curve is plotted based on the concentration of the standard and the corresponding absorbance value. Then, the actual concentrations of motilin, gastrin, 5-hydroxytryptamine, and tumor necrosis factor-α in serum are calculated based on the absorbance value of the sample.

[0045] After blood collection, the rats were immediately euthanized by overdose anesthesia or cervical dislocation. The abdominal cavity was quickly opened, and the cardia and pylorus were ligated before the entire stomach was removed. The stomach cavity was cut along the greater curvature, and the contents were gently rinsed with pre-cooled physiological saline to remove them. The stomach was then laid flat on filter paper on an ice tray to observe the general condition of the gastric mucosa. Then, a tissue block of approximately 1.0 cm × 0.5 cm was cut from the antrum of each rat and immediately fixed in 4% paraformaldehyde solution for more than 24 hours.

[0046] Fixed gastric tissue underwent routine paraffin embedding and sectioning: after dehydration with a gradient of ethanol (70%, 80%, 90%, 95%, 100%), clearing with xylene, paraffin embedding, and then cutting into continuous sections with a thickness of 5 micrometers using a paraffin microtome. After spreading and mounting, the sections were baked in a 60℃ incubator for 2 hours. Subsequently, hematoxylin-eosin staining was performed: sections were routinely dewaxed to water (xylene dewaxing, gradient ethanol hydration), stained with hematoxylin for 5-10 minutes, rinsed with tap water to regain blue color, differentiated with 1% hydrochloric acid ethanol for a few seconds, rinsed with water, counterstained with eosin for 2-3 minutes, rinsed with water, dehydrated with gradient ethanol, cleared with xylene, and mounted with neutral resin. The morphological structure of the gastric mucosa tissue was observed under an optical microscope after staining.

[0047] The degree of gastric mucosal damage was semi-quantitatively analyzed using pathological scoring. The scoring was based on the following four aspects: 1. Congestion: No congestion is 0 points; mild congestion with a small amount of vasodilation is 1 point; moderate congestion with obvious vasodilation is 2 points; severe congestion with severe vasodilation is 3 points.

[0048] 2. Edema: No edema is 0 points; mild edema of the submucosal layer and widening of the interstitial space is 1 point; moderate edema of the submucosal layer and loose structure is 2 points; severe edema of the submucosal layer and severely loose structure is 3 points.

[0049] 3. Erosion: No erosion is 0 points; mild damage to the epithelial surface is 1 point; partial loss of the mucosal layer is 2 points; extensive loss of the mucosal layer is 3 points.

[0050] 4. Bleeding: No bleeding is 0 points; a small amount of red blood cell exudation is 1 point; visible obvious bleeding foci are 2 points; large area or diffuse bleeding is 3 points. Add up the four scores, the higher the total score, the more severe the gastric mucosal damage.

[0051] All experimental data were analyzed using statistical software. Quantitative data are expressed as mean ± standard deviation. One-way ANOVA was used for comparisons among multiple groups, and the minimum significance test was used for pairwise comparisons between groups. A p-value < 0.05 was considered statistically significant. Results are shown in Table 1. Table 1. Comparison of behavioral scores, serum indicators, and gastric mucosal pathological scores of rats in each group (n=20)

[0052] As shown in Table 1, compared with the blank control group, the behavioral scores of rats in the model control group were significantly lower (P<0.05), the serum motilin and gastrin levels were significantly decreased, the levels of 5-hydroxytryptamine and tumor necrosis factor-α were significantly increased, and the gastric mucosal pathological scores were significantly increased (P<0.05). This indicates that the liver qi invading the stomach type of gastric pain model was successfully established, and the rats showed gastric motility disorders, pain sensitivity, inflammatory response and gastric mucosal damage.

[0053] Compared with the model control group, the behavioral scores of rats in the positive control group and each tested drug group were significantly increased (P<0.05), serum motilin and gastrin levels significantly increased (P<0.05), 5-hydroxytryptamine and tumor necrosis factor-α levels significantly decreased (P<0.05), and gastric mucosal pathological scores significantly decreased (P<0.05). This indicates that the positive drug Qizhi Weitong Granules and the various dosage forms of the traditional Chinese medicine composition of this invention have significant therapeutic effects on liver qi invading the stomach type of gastric pain, and can improve rat behavioral abnormalities, regulate gastrointestinal hormone secretion, relieve pain and inflammation, and repair gastric mucosal damage.

[0054] In summary, this invention systematically evaluated the pharmacological effects of the involved traditional Chinese medicine composition by establishing a rat model of liver qi stagnation and stomach pain. Experimental results showed that, compared with the blank control group, the rats in the model control group exhibited significant behavioral abnormalities (decreased behavioral scores), gastrointestinal hormone disorders (decreased serum motilin and gastrin levels), elevated pain-related neurotransmitters (increased serotonin levels), increased release of inflammatory factors (increased tumor necrosis factor-α levels), and significant gastric mucosal pathological damage. This confirmed the successful establishment of the model and its effective simulation of the core pathogenesis of liver qi stagnation and stomach invasion in traditional Chinese medicine.

[0055] After drug intervention, compared with the model control group, the behavioral scores of rats in each drug group were significantly improved, serum motilin and gastrin levels rebounded, 5-hydroxytryptamine and tumor necrosis factor-α levels decreased, and gastric mucosal pathological damage was significantly reduced. This indicates that the traditional Chinese medicine composition of the present invention can effectively regulate gastrointestinal motility, alleviate visceral hypersensitivity, inhibit gastric mucosal inflammatory response, and promote damage repair. Intergroup comparisons showed that the decoction group of Example 1 was superior to the positive control drug (Qi Zhi Wei Tong Granules) in several core indicators, while the granule group of Example 2 and the capsule group of Example 3 also showed efficacy comparable to the positive control drug. Among the three dosage forms, the decoction has a slight advantage in efficacy, which may be related to its good dissolution and absorption characteristics; the granules and capsules also have definite therapeutic effects and are more convenient to store, carry, and take in clinical applications.

[0056] In the description of this specification, the reference to terms such as "embodiment," "various embodiments," etc., indicates that a specific feature, structure, material, or characteristic described in connection with that embodiment or preparation example is included in at least one embodiment of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments.

[0057] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating stomach pain due to liver qi invading the stomach, characterized in that, It is made from the following raw materials in parts by weight: Bupleurum chinense 8-12 parts, Paeonia lactiflora 12-18 parts, Atractylodes macrocephala 10-15 parts, Poria cocos 12-18 parts, Angelica sinensis 10-15 parts, Mentha haplocalyx 3-6 parts, Curcuma longa 6-10 parts, Corydalis yanhusuo 10-15 parts, Glycyrrhiza uralensis 4-6 parts, Citrus medica 8-12 parts, Cyperus rotundus 8-12 parts, Bletilla striata 8-12 parts, and Sepia esculenta 15-25 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The weight proportions of each raw material are as follows: Bupleurum 10 parts, White Peony Root 15 parts, Atractylodes Macrocephala 12 parts, Poria 15 parts, Angelica Sinensis 12 parts, Peppermint 5 parts, Curcuma Rhizome 8 parts, Corydalis Rhizome 12 parts, Licorice Root 5 parts, Citrus Citrus Fruit 10 parts, Bletilla Rhizome 10 parts, Cyperus Rhizome 10 parts, and Cuttlebone 20 parts.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The licorice mentioned is roasted licorice.

4. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, Includes the following steps: (1) Weigh each raw material according to the ratio and soak it in water; (2) Boil the soaked raw materials over high heat, then simmer over low heat, and filter the liquid. (3) Add water to the dregs and decoct again. Combine the decoctions from the two decoctions to obtain the final product.

5. The preparation method according to claim 4, characterized in that, The soaking time in step (1) is 20 to 40 minutes.

6. The preparation method according to claim 4, characterized in that, The simmering time in step (2) is 25 to 35 minutes.

7. The traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, The traditional Chinese medicine composition is in the form of decoction, powder, pill, capsule or granule.

8. The traditional Chinese medicine composition according to claim 7, characterized in that, The dosage of the powder, pill, capsule or granule is 8 to 12 grams per administration, based on the amount of raw medicinal material.

9. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for treating stomach pain of the liver-qi invading the stomach type.

10. The application according to claim 9, characterized in that, The stomach pain caused by liver qi invading the stomach includes one or more of the following symptoms: epigastric distension and pain, pain radiating to the hypochondria, belching, acid reflux and heartburn, irritability, frequent sighing, chest tightness during menstruation, and excessive menstruation.

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