A traditional Chinese medicine preparation for treating functional dyspepsia and its preparation method

Abstract

This invention relates to a traditional Chinese medicine preparation for treating functional dyspepsia and its preparation method. The traditional Chinese medicine preparation is made from the following raw materials in parts by weight: Pinellia ternata 200-781 parts, Coptis chinensis 50-365 parts, Scutellaria baicalensis 100-521 parts, Zingiber officinale 150-625 parts, Panax ginseng 50-313 parts, Glycyrrhiza uralensis 100-417 parts, Ziziphus jujuba 150-625 parts, and Citrus aurantium 150-521 parts. The traditional Chinese medicine preparation of this invention has a good therapeutic effect on functional dyspepsia, and the preparation method of this traditional Chinese medicine preparation is simple and suitable for large-scale production and promotion.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine and relates to a traditional Chinese medicine preparation for treating functional dyspepsia and its preparation method. Background Technology

[0002] Functional dyspepsia (FD) is a common functional gastrointestinal disorder with a global incidence of 7%–45%. Symptoms include upper abdominal pain, early satiety, belching, nausea, vomiting, postprandial fullness and discomfort, and upper abdominal burning sensation. The development of FD symptoms is often related to gastrointestinal motility disorders, visceral hypersensitivity, alterations in gastrointestinal mucosa and immune function, changes in gut microbiota, and psychological factors. These various pathophysiological mechanisms are not entirely independent but rather interact and influence each other. Abnormal gut-brain interaction caused by multiple factors is a crucial mechanism in the occurrence and development of FD.

[0003] FD is a typical disease under the biopsychosocial medical model. Abnormal central regulation is involved in overactive visceral sensation and gastrointestinal motility disorders. Patients often have psychological disorders such as anxiety, depression, and somatization disorder.

[0004] Postprandial discomfort syndrome (PMS) is a clinical subtype of functional dyspepsia, characterized by a cluster of dyspeptic symptoms such as postprandial fullness and early satiety, often accompanied by nausea and belching. It accounts for approximately 90% of patients with functional dyspepsia and is the main syndrome type of functional dyspepsia.

[0005] Febrile dyspepsia (FD) falls under the categories of "abdominal distension" and "stomachache" in Traditional Chinese Medicine (TCM), and is one of the diseases where TCM has a strong advantage in treatment. In recent years, significant progress has been made in both basic research and clinical practice regarding TCM treatment of FD. The principles of strengthening the spleen and stomach, regulating qi and relieving stagnation, and warming the middle jiao and dispelling cold have provided more options for the treatment of FD with certain decoctions (such as Xiangsha Liujunzi Decoction and Chaihu Shugan Powder). Currently, Western medicine mainly treats FD with drugs that increase gastric motility, inhibit gastric acid, and have antidepressant and anti-Helicobacter pylori effects.

[0006] Therefore, it is necessary to find traditional Chinese medicines that have mild effects, multiple components, multiple targets, and multiple pathways to treat functional dyspepsia. Summary of the Invention

[0007] To address the aforementioned problems and deficiencies, this invention provides a traditional Chinese medicine preparation. This preparation is made from the following traditional Chinese medicine raw materials: Pinellia ternata, Coptis chinensis, Scutellaria baicalensis, dried ginger, ginseng, licorice, jujube, and Citrus aurantium. It has a good therapeutic effect on functional dyspepsia and postprandial discomfort syndrome.

[0008] This invention relates to a traditional Chinese medicine preparation, with Pinellia ternata as the principal ingredient to harmonize the stomach, relieve nausea and vomiting, and Scutellaria baicalensis and Coptis chinensis as the bitter and cold herbs to purge heat, and Zingiber officinale as the pungent and warm herbs to dispel cold and expel pathogenic factors stagnating in the stomach, serving as the assistant ingredients. Ginseng, Citrus aurantium, Ziziphus jujuba, and Glycyrrhiza uralensis are added to warm the middle jiao, strengthen the spleen, regulate qi, relieve bloating, and dispel masses and accumulations, while also counteracting the bitter and cold nature of Scutellaria baicalensis and Coptis chinensis. The entire formula works synergistically to open up the stomach, regulate qi, harmonize the stomach, relieve nausea and vomiting, and eliminate fullness and distension. It is suitable for functional dyspepsia causing abdominal distension and a mixture of cold and heat symptoms, including abdominal distension, stomach pain, nausea, vomiting, poor appetite, belching, constipation or diarrhea with borborygmus, a red or pale tongue, a white or yellow coating, and a wiry or slippery pulse. The combined effects of these herbs have a synergistic effect.

[0009] To overcome the above-mentioned deficiencies of the prior art, the present invention provides a traditional Chinese medicine preparation for treating functional dyspepsia, which is made from the following traditional Chinese medicine raw materials in parts by weight: 200-781 parts of Pinellia ternata, 50-400 parts of Coptis chinensis, 100-521 parts of Scutellaria baicalensis, 150-625 parts of Zingiber officinale, 50-313 parts of Panax ginseng, 100-417 parts of Glycyrrhiza uralensis, 150-625 parts of Ziziphus jujuba, and 150-521 parts of Citrus aurantium.

[0010] According to one embodiment of the present invention, the traditional Chinese medicine preparation of the present invention is made from the following traditional Chinese medicine raw materials in parts by weight: 200-600 parts of Pinellia ternata, 50-365 parts of Coptis chinensis, 100-400 parts of Scutellaria baicalensis, 150-550 parts of dried ginger, 50-300 parts of ginseng, 100-350 parts of licorice, 150-450 parts of jujube, and 150-450 parts of Citrus aurantium.

[0011] Preferably, the components of the traditional Chinese medicine preparation of the present invention are: 250-500 parts of Pinellia ternata, 100-300 parts of Coptis chinensis, 200-350 parts of Scutellaria baicalensis, 250-400 parts of Zingiber officinale, 100-200 parts of Panax ginseng, 150-300 parts of Glycyrrhiza uralensis, 250-400 parts of Ziziphus jujuba, and 200-350 parts of Citrus aurantium;

[0012] More preferably, the components of the traditional Chinese medicine preparation of the present invention are: 300-450 parts of Pinellia ternata, 200-300 parts of Coptis chinensis, 200-300 parts of Scutellaria baicalensis, 300-400 parts of Zingiber officinale, 150-200 parts of Panax ginseng, 150-250 parts of Glycyrrhiza uralensis, 300-400 parts of Ziziphus jujuba, and 250-350 parts of Citrus aurantium.

[0013] Most preferably, the traditional Chinese medicine preparation of the present invention is made from the following traditional Chinese medicine raw materials in parts by weight:

[0014] 446 parts of Pinellia ternata, 209 parts of Coptis chinensis, 298 parts of Scutellaria baicalensis, 357 parts of dried ginger, 179 parts of ginseng, 238 parts of licorice, 357 parts of jujube, and 298 parts of Citrus aurantium.

[0015] According to one embodiment of the present invention, the traditional Chinese medicine preparation of the present invention is a traditional Chinese medicine preparation type, and the traditional Chinese medicine preparation may also include pharmaceutical excipients as needed.

[0016] According to one embodiment of the present invention, the traditional Chinese medicine preparation is granules.

[0017] According to one embodiment of the present invention, the pharmaceutical excipient is selected from one, two or three of dextrin, maltodextrin or sucralose.

[0018] This invention further provides a method for preparing the aforementioned traditional Chinese medicine preparation, comprising the following steps:

[0019] The formula uses eight Chinese medicinal herbs: Pinellia ternata, Coptis chinensis, Scutellaria baicalensis, dried ginger, ginseng, licorice, jujube, and Citrus aurantium.

[0020] Preparation steps of Coptis chinensis: Coptis chinensis is extracted by reflux with ethanol, and the extract is concentrated under reduced pressure;

[0021] Ginseng preparation steps: Ginseng is added to ethanol for reflux extraction, and the extract is concentrated under reduced pressure;

[0022] Water extraction steps: Boil the remaining six Chinese medicinal herbs in water, centrifuge the extract, concentrate it, and obtain the concentrated water extract.

[0023] The Coptis chinensis concentrate, ginseng concentrate and water extract concentrate are combined to prepare a traditional Chinese medicine preparation.

[0024] According to a further embodiment, the remaining six Chinese medicinal materials are first added to the dregs of the ginseng and berberine extracted with alcohol, then water is added and decocted, the extract is centrifuged and concentrated to obtain a concentrated water extract.

[0025] In a preferred embodiment, in the preparation step of Coptis chinensis, 1-20 times the amount of ethanol is added, with an ethanol concentration of 1-80%, and the mixture is heated under reflux for 1-3 times, each time for 0.5-6 hours, and concentrated to a relative density of 1.05-1.16; in the preparation step of ginseng, 1-20 times the amount of ethanol is added, with an ethanol concentration of 1-80%, and the mixture is heated under reflux for 1-3 times, each time for 0.5-6 hours, and concentrated to a relative density of 1.05-1.16; in the water extraction step, 1-20 times the amount of water is added, and the mixture is decocted in water for 1-3 times, each time for 0.5-6 hours, and concentrated to a relative density of 1.05-1.16;

[0026] More preferably, in the preparation step of Coptis chinensis, Coptis chinensis is extracted three times with 8 times the amount of 70% ethanol, heated and refluxed for 1 hour each time, filtered, and the extract is concentrated under reduced pressure to a relative density of 1.05-1.16; in the preparation step of ginseng, ginseng is extracted three times with 8 times the amount of 50% ethanol, heated and refluxed for 2 hours each time, filtered, and the extract is concentrated under reduced pressure to a relative density of 1.05-1.16; in the water extraction step, Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, Citrus aurantium, or the residue after ethanol extraction of ginseng and Coptis chinensis, is decocted three times with 8 times the amount of water, each time for 1 hour, the extract is centrifuged, concentrated, and concentrated to a relative density of 1.05-1.16; the Coptis chinensis concentrate, ginseng concentrate, and water extract concentrate are combined to prepare a traditional Chinese medicine preparation.

[0027] According to one embodiment of the present invention, the traditional Chinese medicine preparation of the present invention is a granule, and the preparation method of the granule includes the following steps:

[0028] (1) Add 1-16 times the amount of 10-80% ethanol to Coptis chinensis, heat and reflux to extract 1-3 times, each time for 1-3 hours, filter, recover ethanol from the filtrate under reduced pressure, and concentrate to a relative density of 1.05-1.16;

[0029] (2) Add 1-16 times the amount of 10-70% ethanol to ginseng, heat and reflux to extract 1-3 times, 1-3 hours each time, filter, recover ethanol from the filtrate under reduced pressure, and concentrate to a relative density of 1.05-1.16;

[0030] (3) Combine Coptis chinensis and ginseng concentrate, spray dry to obtain Coptis chinensis and ginseng spray-dried powder;

[0031] (4) Prepared Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and immature bitter orange are decocted with 1-20 times the amount of water for 1-3 times, each time for 1-3 hours. The extract is centrifuged or left to stand for 4-12 hours, filtered, and the filtrate is concentrated under reduced pressure to a relative density of 1.05-1.16. The concentrate is spray-dried to obtain a six-ingredient spray-dried powder of prepared Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and immature bitter orange.

[0032] (5) Mix the sprayed powder of Coptis chinensis and ginseng, the sprayed powder of Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and Citrus aurantium with an appropriate amount of dextrin or maltodextrin and sucralose, and granulate to obtain granules.

[0033] According to one embodiment, in step (4) above, ginseng and the residue of cyperus rotundus extracted with alcohol are first added to Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and immature bitter orange. Then, 1-20 times the amount of water is added, and the mixture is decocted 1-3 times, each time for 1-3 hours. The extract is centrifuged or left to stand for 4-12 hours, filtered, and the filtrate is concentrated under reduced pressure to a relative density of 1.05-1.16. The concentrate is spray-dried to obtain a six-ingredient spray-dried powder of Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and immature bitter orange.

[0034] Preferably, in step (1) above, Coptis chinensis is added with 8 times the amount of 70% ethanol, heated and refluxed three times for 1 hour each time, filtered, and the ethanol is recovered from the filtrate under reduced pressure and concentrated to a relative density of 1.05~1.16.

[0035] Preferably, in step (2) above, ginseng is added to 8 times the amount of 50% ethanol, heated and refluxed three times for 2 hours each time, filtered, and the ethanol is recovered from the filtrate under reduced pressure and concentrated to a relative density of 1.05~1.16.

[0036] Preferably, in step (3) above, Coptis chinensis and ginseng concentrate are combined and spray-dried.

[0037] Preferably, in step (4) above, Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, Citrus aurantium and / or the residue after ginseng and Coptis chinensis alcohol extraction are added, and 8 times the amount of water is added. The mixture is decocted 3 times, 1 hour each time. The extract is centrifuged, and the centrifuged liquid is concentrated under reduced pressure to a relative density of 1.05-1.16. The concentrate is then spray-dried.

[0038] Preferably, in step (5) above, the spray-dried powder of Coptis chinensis and ginseng, the spray-dried powder of Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and Citrus aurantium are mixed with an appropriate amount of dextrin or maltodextrin and sucralose, and then granulated to obtain granules.

[0039] This invention further provides the application of the aforementioned traditional Chinese medicine preparation in the preparation of drugs for functional dyspepsia, postprandial discomfort syndrome (mixed cold and heat syndrome), gastrointestinal motility promotion, gastric emptying, gastroparesis, gastric ulcer, anti-inflammatory or analgesic purposes.

[0040] The following are explanations and descriptions of the terms used in this invention: The raw materials involved in the traditional Chinese medicine preparations / formulations for treating functional dyspepsia, postprandial discomfort syndrome (mixed cold and heat syndrome), promoting gastrointestinal motility, gastric emptying, gastroparesis, gastric ulcers, and for anti-inflammatory or analgesic purposes in this invention are as follows:

[0041] Pinellia ternata (Thunb.) Breit., a plant in the Araceae family, is a dried tuber. It is pungent and warm in nature. It enters the spleen, stomach, and lung meridians. It is used for cough and asthma with excessive phlegm, dizziness and palpitations due to phlegm retention, vertigo due to wind-phlegm, and headache due to phlegm syncope.

[0042] Coptis chinensis is the dried rhizome of the Ranunculaceae plant Coptis chinensis Franch. It is bitter and cold in nature. It enters the heart, spleen, stomach, liver, gallbladder, and large intestine meridians. It is used for damp-heat stagnation, vomiting and acid regurgitation, diarrhea, jaundice, high fever with delirium, excessive heart fire, restlessness and insomnia, palpitations, hematemesis due to blood heat, red eyes, toothache, diabetes, carbuncles and boils; externally, it is used to treat eczema, damp sores, and ear discharge.

[0043] Scutellaria baicalensis is the dried root of the plant Scutellaria baicalensis Georgi, belonging to the Lamiaceae family. It is bitter and cold in nature. It enters the Lung, Gallbladder, Spleen, Large Intestine, and Small Intestine meridians. It is used for damp-heat syndrome, summer-heat syndrome, chest tightness and nausea, damp-heat abdominal distension, diarrhea, jaundice, cough due to lung heat, high fever and thirst, hematemesis due to blood heat, carbuncles and boils, and threatened abortion.

[0044] Dried ginger is the dried rhizome of *Zingiber officinale* Rosc., a plant in the ginger family (Zingiberaceae). It is pungent and hot in nature. It enters the spleen, stomach, kidney, heart, and lung meridians. It is used for cold pain in the epigastrium and abdomen, vomiting and diarrhea, cold limbs and weak pulse, and cough with wheezing due to cold phlegm.

[0045] Ginseng is the dried root and rhizome of Panax ginseng CA Mey., a plant belonging to the Araliaceae family. It is sweet, slightly bitter, and slightly warm in nature. It enters the spleen, lung, heart, and kidney meridians. It is used for weakness and exhaustion, cold limbs and weak pulse, poor appetite due to spleen deficiency, cough and asthma due to lung deficiency, thirst due to fluid depletion, internal heat and thirst, deficiency of qi and blood, chronic illness and emaciation, palpitations and insomnia, impotence and cold uterus.

[0046] Licorice is the dried root and rhizome of *Glycyrrhiza uralensis* Fisch., a plant in the legume family. It is sweet and neutral in nature. It enters the heart, lung, spleen, and stomach meridians. It is used for spleen and stomach weakness, fatigue, palpitations, shortness of breath, cough with excessive phlegm, abdominal pain, spasms and pain in the limbs, carbuncles and boils, and to alleviate the toxicity and harshness of other medications.

[0047] Jujube is the dried, ripe fruit of the plant *Ziziphus jujuba* Mill., belonging to the Rhamnaceae family. It is sweet and warm in nature. It enters the spleen, stomach, and heart meridians. It is used for spleen deficiency with poor appetite, fatigue, loose stools, and hysteria in women.

[0048] Citrus aurantium L., a plant of the Rutaceae family, is the dried young fruit of Citrus aurantium L. and its cultivated varieties. It is bitter, pungent, sour, and slightly cold in nature. It enters the spleen and stomach meridians. It is used for food stagnation, abdominal distension and pain, tenesmus after diarrhea, constipation, phlegm obstruction, chest pain, chest tightness, and organ prolapse.

[0049] The traditional Chinese medicine preparation of the present invention is preferably in the form of a unit dose. The oral preparation is selected from one of capsules, tablets, drop pills, granules, concentrated pills, oral liquids, and compound preparations. The injectable preparation is selected from one of injection solutions, lyophilized powder injections, and aqueous injections.

[0050] The traditional Chinese medicine preparations of the present invention, when administered orally, may contain commonly used excipients such as binders, fillers, diluents, tableting agents, lubricants, disintegrants, colorants, flavoring agents, and humectants. If necessary, the tablets may be coated.

[0051] Suitable fillers include cellulose, mannitol, lactose, and other similar fillers. Suitable disintegrants include starch, polyvinylpyrrolidone, and starch derivatives such as sodium glycolate starch. Suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulfate.

[0052] The traditional Chinese medicine preparations of this invention can be prepared into solid oral traditional Chinese medicine preparations using common methods such as mixing, filling, and tableting. Repeated mixing allows the active substances to be distributed throughout those traditional Chinese medicine preparations that use a large amount of filler.

[0053] Oral liquid formulations may take the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs, or may be a dried product that can be reconstituted with water or other suitable carriers before use. Such liquid formulations may contain conventional additives such as suspending agents, for example sorbitol, syrups, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel, or hydrogenated edible fats; emulsifiers, such as lecithin, dehydrated sorbitan monooleate, or gum arabic; non-aqueous carriers (which may include edible oils such as almond oil, fractionated coconut oil), oily esters such as glycerol, propylene glycol, or ethanol; preservatives, such as methylparaben or propylparaben or sorbic acid; and, if desired, conventional flavorings or colorings.

[0054] For injectable formulations, the prepared liquid dosage form contains the active ingredient of this invention and a sterile carrier. Depending on the carrier and concentration, this compound can be suspended or dissolved. Solution preparation typically involves dissolving the active ingredient in a carrier, filtering and sterilizing it before filling it into a suitable vial or ampoule, and then sealing it. Excipients such as a local anesthetic, preservatives, and buffers can also be dissolved in this carrier. To improve its stability, this herbal preparation can be frozen after filling into the vial, and water can be removed under vacuum.

[0055] The traditional Chinese medicine preparation of the present invention may selectively incorporate a suitable drug-acceptable carrier during preparation. The drug-acceptable carrier is selected from: mannitol, sorbitol, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, cysteine ​​hydrochloride, thioglycolic acid, methionine, vitamin C, disodium EDTA, calcium sodium EDTA, carbonates of monovalent alkali metals, acetates, phosphates or aqueous solutions thereof, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acids, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivatives, cellulose and its derivatives, alginate, gelatin, polyvinylpyrrolidone, glycerol, Twenty-80, agar, calcium carbonate, calcium bicarbonate, surfactants, polyethylene glycol, dextrin, maltodextrin, cyclodextrin, β-cyclodextrin, phospholipids, kaolin, talc, calcium stearate, magnesium stearate, etc.

[0056] Flavoring agents are used to improve the taste of granules. Common sweeteners include stevia, aspartame, and sucralose.

[0057] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions, or alterations can be made without departing from the basic technical concept of the present invention.

[0058] Beneficial technical effects of the present invention:

[0059] 1. The traditional Chinese medicine preparation of this invention is composed of eight herbs: Pinellia ternata, Coptis chinensis, Scutellaria baicalensis, Zingiber officinale, Panax ginseng, Glycyrrhiza uralensis, Ziziphus jujuba, and Citrus aurantium. Pharmacological studies have found that the traditional Chinese medicine group of this invention mainly intervenes in FD through three modules: NOS, 5-HT, and immunity / inflammation. It may play a role in improving anxiety and depression. Furthermore, animal model studies of FD have shown that the traditional Chinese medicine preparation of this invention can restore abnormally secreted brain-gut peptides to normal levels.

[0060] 2. This invention verifies that the traditional Chinese medicine preparation of this invention has the effect of treating functional dyspepsia and postprandial discomfort syndrome.

[0061] 3. Animal experiments of this invention verify that the herbal preparation of this invention can promote the secretion of MTL and GAS in FD rats, inhibit the secretion of VIP and CGRP, and increase the expression of 5-HT in the gastric antrum and hypothalamic tissues of rats. The herbal preparation of this invention may exert its therapeutic effect on FD by adjusting the normal levels of brain-gut peptides. At the protein level, it is verified that the herbal preparation of this invention inhibits the expression of Akt and p-Akt proteins in gastric tissue along the PI3K-Akt / NOS signaling pathway, thereby inhibiting NOS expression and further reducing the release of the inhibitory neurotransmitter NO, thus exerting its therapeutic effect.

[0062] 4. The experimental results of this invention show that the traditional Chinese medicine preparation of this invention can inhibit ulcers, promote gastric emptying, increase small intestinal propulsion, and has no significant effect on gastric juice secretion, acidity and gastric enzyme activity. It has analgesic and anti-inflammatory effects. Attached Figure Description

[0063] Figure 1 : Figure 1 A indicates that the contents of the capsule dosage form have clumps. Figure 1 B indicates a darker capsule shell color for the capsule dosage form.

[0064] Figure 2 : Figure 2 A represents the MTL content in rats of each group after drug administration. ±s, n=6); Figure 2 B represents the GAS content (±s, n=6) in rats of each group after drug administration.

[0065] Figure 3 : Figure 3 A represents the serum VIP content of rats in each group after drug administration. ±s, n=6); Figure 3 B represents the serum CGRP content (±s, n=6) of rats in each group after drug administration;

[0066] Figure 4 : Figure 4 A represents the expression of 5-HT in rat gastric antrum tissue. ±s, n=6); Figure 4 B represents the expression of 5-HT in rat hypothalamic tissue (±s, n=6).

[0067] Figure 5 The effects of the traditional Chinese medicine preparation of this invention on 5-HT staining of the gastric antrum and hypothalamus of rats in various groups;

[0068] Figure 6 AMS content in rats of each group after drug administration ( ±s, n=6);

[0069] Figure 7 NOS activity in rats of different groups after drug administration ( ±s, n=6);

[0070] Figure 8 Western blot was used to detect the expression of Akt and p-Akt proteins in the gastric tissue of rats in each group.

[0071] Figure 9 : Figure 9 A represents the effect of drug administration on Akt protein expression in the gastric tissue of rats in each group; Figure 9 B represents the effect of drug administration on the expression of p-Akt protein in the gastric tissue of rats in each group. Detailed Implementation

[0072] The present invention is further illustrated by the following examples, but these are not intended to limit the invention. Example 1

[0073] Pinellia ternata 446g, Coptis chinensis 209g, Scutellaria baicalensis 298g, Zingiber officinale 357g, Panax ginseng 179g, Glycyrrhiza uralensis 238g, Ziziphus jujuba 357g, Citrus aurantium 298g

[0074] Take the following eight Chinese medicinal herbs according to the above weights: Pinellia ternata, Coptis chinensis, Scutellaria baicalensis, dried ginger, ginseng, licorice, jujube, and Citrus aurantium. Extract Coptis chinensis with 8 times the amount of 70% ethanol by heating and reflux three times, 1 hour each time. Concentrate the extract under reduced pressure to a relative density of 1.05-1.16. Extract Ginseng with 8 times the amount of 50% ethanol by heating and reflux three times, 2 hours each time. Concentrate the extract under reduced pressure to a relative density of 1.05-1.16. Add 8 times the amount of water to the residue of ginseng and Coptis chinensis, and decoct the remaining six herbs three times, 1 hour each time. Centrifuge and concentrate the extract to a relative density of 1.05-1.16. Combine the concentrated Coptis chinensis extract, concentrated ginseng extract, and concentrated water extract to obtain the Chinese medicine preparation. Example 2

[0075] 200g of prepared Pinellia ternata, 50g of Coptis chinensis, 100g of Scutellaria baicalensis, 150g of dried ginger, 50g of ginseng, 100g of licorice root, 150g of jujube, and 150g of immature bitter orange.

[0076] Take the following eight Chinese medicinal herbs according to the above weights: Pinellia ternata, Coptis chinensis, Scutellaria baicalensis, Zingiber officinale, Panax ginseng, Glycyrrhiza uralensis, Ziziphus jujuba, and Citrus aurantium. Extract Coptis chinensis with 6 times the amount of 40% ethanol by heating and reflux three times, 1 hour each time. Concentrate the extract under reduced pressure to a relative density of 1.05-1.16. Extract Panax ginseng with 6 times the amount of 40% ethanol by heating and reflux three times, 2 hours each time. Concentrate the extract under reduced pressure to a relative density of 1.05-1.16. Add 8 times the amount of water to the residue of Panax ginseng and Coptis chinensis, and decoct three times, 1 hour each time. Centrifuge and concentrate the extract to a relative density of 1.05-1.16. Combine the concentrated Coptis chinensis extract, concentrated Panax ginseng extract, and concentrated water extract to obtain the Chinese medicine preparation. Example 3

[0077] 600g of prepared Pinellia ternata, 400g of Coptis chinensis, 400g of Scutellaria baicalensis, 550g of dried ginger, 300g of ginseng, 350g of licorice root, 450g of jujube, and 450g of immature bitter orange.

[0078] Take the following eight Chinese medicinal herbs according to the above weights: Pinellia ternata, Coptis chinensis, Scutellaria baicalensis, dried ginger, ginseng, licorice, jujube, and Citrus aurantium. Extract Coptis chinensis with 12 times the amount of 80% ethanol by heating and reflux three times, 3 hours each time. Concentrate the extract under reduced pressure to a relative density of 1.05-1.16. Extract Ginseng with 12 times the amount of 75% ethanol by heating and reflux three times, 2 hours each time. Concentrate the extract under reduced pressure to a relative density of 1.05-1.16. Add 12 times the amount of water to the residue of ginseng and Coptis chinensis, and decoct the remaining six herbs three times, 1 hour each time. Centrifuge and concentrate the extract to a relative density of 1.05-1.16. Combine the concentrated Coptis chinensis extract, concentrated ginseng extract, and concentrated water extract to obtain the Chinese medicine preparation. Example 4

[0079] 250g of prepared Pinellia ternata, 100g of Coptis chinensis, 200g of Scutellaria baicalensis, 250g of dried ginger, 100g of ginseng, 150g of licorice root, 250g of jujube, and 200g of immature bitter orange.

[0080] Take the following eight Chinese medicinal herbs according to the above weights: Pinellia ternata, Coptis chinensis, Scutellaria baicalensis, Zingiber officinale, Panax ginseng, Glycyrrhiza uralensis, Ziziphus jujuba, and Citrus aurantium. Extract Coptis chinensis twice with 10 times the amount of 70% ethanol, heating and refluxing for 1 hour each time. Concentrate the extract under reduced pressure to a relative density of 1.05-1.16. Extract Panax ginseng twice with 10 times the amount of 50% ethanol, heating and refluxing for 2 hours each time. Concentrate the extract under reduced pressure to a relative density of 1.05-1.16. Add 10 times the amount of water to the residue of Panax ginseng and Coptis chinensis, and the remaining six herbs, decoct twice with 10 times the amount of water, each time for 1 hour. Centrifuge and concentrate the extract to a relative density of 1.05-1.16. Combine the concentrated Coptis chinensis extract, concentrated Panax ginseng extract, and concentrated water extract to obtain the Chinese medicine preparation. Example 5

[0081] 500g of prepared Pinellia ternata, 300g of Coptis chinensis, 350g of Scutellaria baicalensis, 400g of dried ginger, 200g of ginseng, 300g of licorice root, 400g of jujube, and 350g of immature bitter orange.

[0082] Take the following eight Chinese medicinal herbs according to the above weights: Pinellia ternata, Coptis chinensis, Scutellaria baicalensis, Zingiber officinale, Panax ginseng, Glycyrrhiza uralensis, Ziziphus jujuba, and Citrus aurantium. Extract Coptis chinensis once with 6 times the amount of 40% ethanol, heating and refluxing for 3 hours each time. Concentrate the extract under reduced pressure to a relative density of 1.05-1.16. Extract Panax ginseng once with 6 times the amount of 40% ethanol, heating and refluxing for 3 hours each time. Concentrate the extract under reduced pressure to a relative density of 1.05-1.16. Add 8 times the amount of water to the residue of Panax ginseng and Coptis chinensis, and the remaining six herbs, decoct once with 8 times the amount of water, each time for 3 hours. Centrifuge and concentrate the extract to a relative density of 1.05-1.16. Combine the concentrated Coptis chinensis extract, concentrated Panax ginseng extract, and concentrated water extract to obtain the Chinese medicine preparation.

[0083] Example 6: Capsules

[0084] Pinellia ternata 781g, Coptis chinensis 365g, Scutellaria baicalensis 521g, Zingiber officinale 625g, Panax ginseng 313g, Glycyrrhiza uralensis 417g, Ziziphus jujuba 625g, Citrus aurantium 521g

[0085] Prepare 1000 capsules. (1) Coptis chinensis: Add 8 times the amount of 70% ethanol, heat and reflux to extract 3 times, 1 hour each time, filter, combine the filtrates, recover the ethanol under reduced pressure, spray dry the concentrated liquid into fine powder, and set aside for later use; (2) Ginseng: Add 8 times the amount of 50% ethanol, heat and reflux to extract 3 times, 2 hours each time, filter, combine the filtrates, recover the ethanol under reduced pressure, spray dry the concentrated liquid into fine powder, and set aside for later use; (3) Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, Citrus aurantium and ginseng and Coptis chinensis residue after alcohol extraction, add 8 times the amount of water, decoct 3 times, 1 hour each time, let stand for 24 hours to settle, filter, combine the filtrates, concentrate under reduced pressure to 1.05-1.16, spray dry the concentrated liquid into fine powder, and set aside for later use. Combine the dried fine powders of (1), (2) and (3), mix, granulate with 50% ethanol, dry at 60℃, granulate, and fill into 0.5g / capsule capsules to obtain the product.

[0086] Example 7: Granules

[0087] Pinellia ternata 446g, Coptis chinensis 209g, Scutellaria baicalensis 298g, Zingiber officinale 357g, Panax ginseng 179g, Glycyrrhiza uralensis 238g, Ziziphus jujuba 357g, Citrus aurantium 298g

[0088] Coptis chinensis was extracted three times with 8 times the amount of 70% ethanol under reflux for 1 hour each time. The extract was filtered, and the ethanol was recovered from the filtrate under reduced pressure. The extract was then concentrated to a relative density of 1.05-1.16 and set aside. Ginseng was extracted three times with 8 times the amount of 50% ethanol under reflux for 2 hours each time. The extract was filtered, and the ethanol was recovered from the filtrate under reduced pressure. The extract was then concentrated to a relative density of 1.05-1.16 and set aside. The Coptis chinensis and ginseng concentrates were combined and spray-dried. Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and Citrus aurantium, or the residue after ethanol extraction with ginseng and Coptis chinensis, were decocted three times with 8 times the amount of water for 1 hour each time. The extract was centrifuged, filtered, and the filtrate was concentrated under reduced pressure to a relative density of 1.05-1.16. The concentrate was then spray-dried and set aside.

[0089] Mix the spray-dried powders of Coptis chinensis, ginseng, and Pinellia ternata with appropriate amounts of dextrin and sucralose to make 1000g of granules.

[0090] Example 8: Granules

[0091] Pinellia ternata 446g, Coptis chinensis 209g, Scutellaria baicalensis 298g, Zingiber officinale 357g, Panax ginseng 179g, Glycyrrhiza uralensis 238g, Ziziphus jujuba 357g, Citrus aurantium 298g

[0092] Coptis chinensis was extracted three times with 8 times the amount of 70% ethanol under reflux for 1 hour each time. The extract was filtered, and the ethanol was recovered from the filtrate under reduced pressure. The extract was then concentrated to a relative density of 1.05-1.16 and set aside. Ginseng was extracted three times with 8 times the amount of 50% ethanol under reflux for 2 hours each time. The extract was filtered, and the ethanol was recovered from the filtrate under reduced pressure. The extract was then concentrated to a relative density of 1.05-1.16 and set aside. The Coptis chinensis and ginseng concentrates were combined and spray-dried. Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and Citrus aurantium, or the residue after ethanol extraction with ginseng and Coptis chinensis, were decocted three times with 8 times the amount of water for 1 hour each time. The extract was centrifuged, filtered, and the filtrate was concentrated under reduced pressure to a relative density of 1.05-1.16. The concentrate was then spray-dried and set aside.

[0093] Mix the spray-dried powders of Coptis chinensis, ginseng, and Pinellia ternata with an appropriate amount of maltodextrin and sucralose to make 1000g of granules.

[0094] Example 9: Screening of Spray Drying Process

[0095] A comparative study was conducted on the spraying and drying of Coptis chinensis and ginseng alone and mixed Coptis chinensis and ginseng in the preparation of granules, so as to determine the optimal experimental process for spraying and drying Coptis chinensis and ginseng together. The experimental data are shown in Table 1 below.

[0096] Table 1. Data from separate spray-drying experiments with Coptis chinensis and ginseng.

[0097]

[0098] As can be seen from Table 1, there are certain differences in the powder yield and the transfer rate of the indicative component berberine hydrochloride between spray-drying Coptis chinensis and ginseng alone and spray-drying together. The powder yield of Coptis chinensis and ginseng spray-drying alone and then combined is between 16.71% and 16.92%, and the transfer rate of berberine hydrochloride is between 65.38% and 65.51%.

[0099] The combined powder yield of Coptis chinensis and ginseng through spray drying is between 17.12% and 17.58%, and the berberine hydrochloride transfer rate is between 68.69% and 68.27%. Furthermore, the combined spray drying process is simpler than the individual spray drying processes, reducing the cleaning steps and simplifying the procedure. Therefore, selecting the combined spray drying process of the Coptis chinensis and ginseng concentrate is the most reasonable approach. Consequently, the combined spray drying process used in the granules of Example 7 is the most appropriate choice.

[0100] Example 10: Screening of excipient types

[0101] The intermediate powder of this product is highly hygroscopic. Based on the excipients commonly used in granules reported in the literature, dextrin and starch were selected as excipients for screening. Evaluation was conducted on two aspects: granule solubility and granule yield. A 1:1 ratio of drug powder to excipient was chosen during the screening process to facilitate observation and evaluation of the excipient's effect on the granules. Specific test results are shown in Table 2 below.

[0102] Table 2. Screening and Analysis of Auxiliary Material Types

[0103]

[0104] Dextrin is a white amorphous powder, odorless, with a slightly sweet taste. It is easily soluble in boiling water and slowly dissolves in cold water. It is safe, non-toxic, inexpensive, and readily available. It is relatively stable in high temperature and high humidity environments. As can be seen from Table 2, dextrin, as a filler for this product, has good adhesion, and the yield and solubility of granules are better than those of starch. Therefore, dextrin was chosen as the filler for this product.

[0105] Comparative Example 1: Dosage Form Screening

[0106] The study will include four different dosage forms, focusing on aspects such as drug loading, patient compliance, and formulation stability.

[0107] Dosage form: concentrated pills; excipients: conventional excipients; drug loading range: 40-60%; daily dose: 10g.

[0108] Dosage form: disintegrating tablets; excipients: xylitol, etc.; drug loading range: 40-60%; daily dose: 10g.

[0109] Dosage form: Capsules; Excipients: None; Daily dose: 12 capsules (4 capsules / time, 3 times / day).

[0110] Dosage form: granules; excipients: sucralose, etc.; drug loading range: 60-90%; daily dosage: 7.5g.

[0111] The results showed that the concentrated pill form had too low a drug loading, resulting in excessive dosage and very poor patient compliance; the disintegrating tablet form was unstable during storage and would soften.

[0112] The capsule shell cannot completely isolate moisture, and the shell itself is also hygroscopic. Combined with the hygroscopic nature of the medicinal ingredients, this leads to severe moisture absorption during accelerated stabilization, resulting in unstable quality of the capsule dosage form. After one month under accelerated stabilization conditions, the capsule color darkened, and the contents clumped (see...). Figure 1 The moisture content of the capsules was 10.3%, exceeding the limit (the Chinese Pharmacopoeia stipulates that the moisture content of capsules should not exceed 9.0%). In addition, the No. 0 capsules were too large, making it difficult for patients to swallow. After taking the capsules, patients experienced a feeling of fullness and poor compliance.

[0113] However, granules are convenient to carry and use, and the addition of sucralose improves the taste, greatly enhancing patient tolerance. Increasing the excipients by 30%–40% facilitates material dispersion, significantly improving granule stability. Taking granules last improves patient compliance. Furthermore, granules offer better stability than other dosage forms, ensuring product quality stability for 24 months. Stability data for granules are shown in Table 3 below.

[0114] Table 3. Experimental data on the stability of granules

[0115]

[0116] Example of Effect E1

[0117] Experimental Methods: Ten-day-old suckling rats were randomly divided into two groups: a normal group (n=8) and a model group (n=14). The normal group received 0.2 mL / rat via gavage at 9:00 AM daily for 6 consecutive days with a 2% sucrose solution. The model group received 0.2 mL / rat via gavage at 9:00 AM daily with a 0.1% iodoacetamide 2% sucrose solution for 6 consecutive days. Afterward, normal feeding conditions remained unchanged. Rats were raised to 3 weeks of age, weaned (cessation of breastfeeding), and the mother rats were removed. The rats were then separated into three cages and fed with conventional feed. Rats were raised to 6 weeks of age; the normal group received normal feeding, while the model group received feed every other day for 14 consecutive days. Starting the day after modeling, the model rats were randomly divided into a model group and a treatment group. Each group received the treatment via gavage at 9:00 AM. The treatment group received a 0.9 g / kg dose of the traditional Chinese medicine preparation solution from Example 1 of this invention via gavage, while the normal and model groups received the same volume of physiological saline via gavage. This treatment was continued for 4 weeks. During the administration period, rats in all groups were fed a normal diet and had free access to purified water. Rats were weighed once daily, and the daily dose administered via gavage was adjusted according to weight changes. After the last administration, rats were fasted for 24 hours and anesthetized with an intraperitoneal injection of 3% sodium pentobarbital (100 mg / kg). Blood was collected from the abdominal aorta, allowed to stand for 30 minutes, and then centrifuged at 4500 rpm for 10 minutes at 4°C. The supernatant was collected and stored at -80°C. Rats were euthanized by cervical dislocation. The gastric cardia and pylorus were ligated on a clean bench, and the entire stomach was removed. The stomach was cut along the greater curvature, and the contents were rinsed with distilled water to a final volume of 20 mL. The stomach was then stored at -80°C for later use. A ring-shaped muscle strip from the gastric antrum 0.5 cm from the pylorus was removed. The rat brain was excised, and the rat cranial cavity was opened on ice. Hippocampal and hypothalamic tissues were collected and fixed in 4% paraformaldehyde solution.

[0118] 1. Determination of serum motilin (MTL) and gastrin (GAS) levels in rats

[0119] The results of rat serum motilin (MTL) levels are shown in Table 4 and Figure 2 As stated in A, the results of gastrin (GAS) content are shown in Table 4 and Figure 2 As shown in B. After administration of the herbal preparation solution of Example 1 of the present invention, the serum MTL and GAS levels in the treated rats were significantly higher than those in the model group (P<0.01). Compared with the normal group, the GAS level in the model group was significantly lower (P<0.01).

[0120] Table 4 Comparison of serum MTL and GAS levels in rats ( ±s, n=6)

[0121]

[0122] Note: Compared with the normal group, **: P < 0.01. Compared with the model group, #: P < 0.05.

[0123] 2. Determination of serum vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) levels in rats.

[0124] The results of rat serum vasoactive intestinal peptide (VIP) levels are shown in Table 5 below. Figure 3 As shown in Figure A; the results of calcitonin gene-related peptide (CGRP) content are shown in Table 5 below. Figure 3 As shown in Figure B. VIP and CGRP are the main inhibitory neurotransmitters in the gastrointestinal tract. VIP inhibits smooth muscle contraction in the digestive tract, slows gastric emptying, inhibits small intestinal motility and electrolyte secretion, and regulates gallbladder pressure by inhibiting gallbladder contraction. Serum CGRP is a potent peptide vasodilator that plays a role in pain transmission; it is abnormally elevated in patients with functional dysplasia (FD). Increased CGRP secretion can increase nociceptive transmission related to pain, leading to visceral hypersensitivity. Figure 3 A and Figure 3 B shows that the levels of VIP and CGRP in the model group rats were significantly higher than those in the normal group and the drug-treated group (P<0.05).

[0125] Table 5 Comparison of serum VIP and CGRP levels in rats of different groups ±s, n=6)

[0126]

[0127] Note: *: P < 0.05 compared with the normal group; #: P < 0.05 compared with the model group.

[0128] 3. Expression of 5-HT in rat hypothalamus and gastric antrum tissue

[0129] The expression of 5-HT in the gastric antrum tissue of rats in each group was detected by IHC method, and the results are expressed as the percentage of positive cells. See Table 6 below for the results. Figure 4 As shown in Figure A, the IHC staining results are as follows: Figure 5 The expression of 5-HT in the hypothalamus tissue of rats in each group was detected by IHC method, and the results are expressed as the percentage of positive cells. See Table 6 below for the results. Figure 4 As shown in B, the IHC staining results are as follows: Figure 5As shown in Table 6, the expression levels of 5-HT in the gastric antrum tissue and hypothalamus of rats in the treatment group (0.9 g / kg of the herbal preparation in Example 1 of this invention) were increased to varying degrees. In particular, the expression level of 5-HT in the hypothalamus was significantly different from that in the model group (P<0.01); the expression level in the gastric antrum tissue was significantly different from that in the model group (P<0.05), while there was no significant difference in expression between the model group and the normal group.

[0130] Table 6. 5-HT expression in gastric antrum and hypothalamic tissue of rats in each group ( ±s, n=6)

[0131]

[0132] Note: Compared with the model group, #: P<0.05, ##: P<0.01.

[0133] 4. Determination of serum amylase (AMS) levels in rats

[0134] Serum amylase (AMS) levels in rats of each group were measured before and after drug administration using a kit. Data analysis showed that the AMS level in the model group decreased significantly after the model was established (P < 0.01), indicating successful model establishment. After drug administration, there was no significant difference in AMS levels between the normal group and the model group, possibly because the rats in the model group recovered spontaneously during the one-month drug administration period, hence the lack of significant difference. Compared with the normal group, the AMS level in the drug administration group (0.9 g / kg of the herbal preparation in Example 1 of this invention) was significantly increased (P < 0.05); compared with the model group, the AMS level in the drug administration group was significantly increased (P < 0.01), showing a significant difference. The comparison of AMS levels in each group of rats before and after drug administration is shown in Table 7 below. Figure 6 As shown.

[0135] Table 7 Comparison of serum AMS levels in rats of different groups ( ±s, n=6)

[0136]

[0137] 5. Assay of nitric oxide synthase (NOS) activity in rat gastric tissue

[0138] Rat stomach tissue was homogenized and prepared into a 10% homogenate solution using physiological saline. The activity of nitric oxide synthase (NOS) in rat stomach tissue was then determined using a chemical method. The results are shown in Table 8 below. Figure 7 As shown in the figure. The results showed that, compared with the model group, the NOS activity in the gastric tissue of rats in the normal group and the drug-treated group (the traditional Chinese medicine preparation (0.9 g / kg) in Example 1 of this invention) was significantly different (P<0.05). NOS catalyzes the formation of NO from L-Arg. The current mainstream view is that increased NO will inhibit gastrointestinal motility, so NOS has a negative regulatory effect.

[0139] Table 8 Comparison of NOS activity in gastric tissue of rats in different groups ( ±s, n=6)

[0140]

[0141] Note: * indicates that compared with the normal group, *: P<0.05; # indicates that compared with the model group, #: P<0.05.

[0142] 6. Determine the expression levels of Akt and p-Akt in gastric tissue of FD rats.

[0143] The expression levels of Akt and p-Akt in gastric tissue of FD rats were determined using Western blotting. The results are as follows: Figure 8 and Figure 9 A and Figure 9 As shown in Figure B, Western blotting results indicated that the average Akt grayscale ratios in the normal group, model group, and drug-treated group were 0.66, 0.73, and 0.66, respectively, while the average p-Akt grayscale ratios were 0.79, 0.92, and 0.73, respectively. The p-Akt expression level was higher in the model group compared to the drug-treated group, and the Akt expression level was also higher. Figure 8 and Figure 9 A and Figure 9 B shows that the protein bands of Akt and p-Akt in the model group are wider and darker than those in the normal group and the drug-treated group.

[0144] The therapeutic effect of the traditional Chinese medicine preparation in Example 1 of this invention on FD may be related to the PI3K-Akt / NOS signaling pathway. By inhibiting the expression of Akt and p-Akt in this pathway, the expression of NOS is inhibited, thereby reducing the release of the inhibitory neurotransmitter NO. NO plays an important role in stimulating gastrointestinal secretion and relaxing gastrointestinal smooth muscle, thus achieving the purpose of treating FD. At the same time, the traditional Chinese medicine preparation of this invention can promote the secretion of AMS, thereby improving the digestive and metabolic function of FD rats, thus playing a certain therapeutic role in FD.

[0145] Example E2: Anti-gastric ulcer effect of the traditional Chinese medicine preparation of the present invention on rats.

[0146] Test animals: Wistar rats: provided by the Animal Breeding Farm of the Chinese Academy of Medical Sciences, certificate number: Medical Animal No. 01-3008; KM mice: provided by the Animal Breeding Farm of the Chinese Academy of Medical Sciences, certificate number: Medical Animal No. 01-3001.

[0147] Dosage: (1) Control group: equal volume of physiological saline.

[0148] (2) Positive control group: each ml contains 4 mg of cimetidine (80 mg / kg);

[0149] (3) Low-dose group: each ml contains 0.25g of raw drug (5g / kg);

[0150] (4) Medium dose group: each ml contains 0.5g of raw drug (10g / kg);

[0151] (5) High-dose group: each ml contains 1g of raw drug (20g / kg);

[0152] 1. Anti-gastric ulcer effect: Effect on water immersion stress ulcers in rats

[0153] Methods: Rats weighing 150-180 grams (both male and female) were used. After fasting (but not water), they were randomly divided into 5 groups. The treatment groups were administered high, medium, and low doses of the traditional Chinese medicine preparation from Example 1 of this invention via gavage. The control group was administered an equal volume of physiological saline via gavage. The positive control group was administered cimetidine via gavage. Thirty minutes after administration, the rats were lightly anesthetized with ether, fixed in a supine position on a test tube rack, and then immersed upright in a constant temperature water bath at 23°C, with the water level at the xiphoid process. After 18 hours, the rats were sacrificed, their abdomens opened, and the pylorus and cardia were ligated. 5 ml of 1% formalin was injected through the proventriculus. The stomach was removed and fixed in a 1% formalin solution for 10 minutes. The stomach was then cut along the greater curvature, and the contents were flushed to examine for ulceration. The total length of the ulcers in millimeters was used as the ulcer index for statistical analysis. The percentage of ulcer inhibition was calculated to evaluate the drug's effect.

[0154]

[0155] Results: The traditional Chinese medicine preparation in Example 1 of this invention can significantly inhibit water immersion stress-induced gastric ulcers, showing a significant difference compared with the control group. The results are shown in Table 9 below.

[0156] Table 9. Effects on water immersion stress-induced gastric ulcers in rats.

[0157]

[0158] Compared with the negative control group: **: P < 0.01, ***: P < 0.001.

[0159] 2. Anti-gastric ulcer effect: Effect on acetic acid-induced gastric ulcers.

[0160] Methods: Rats weighing 150-180g (both male and female) were used and fasted for 12 hours. They were randomly divided into 5 groups: a negative control group, a positive control group (cimetidine), and high, medium, and low dose groups of the traditional Chinese medicine preparation from Example 1 of this invention. The animals were anesthetized with ether in a semi-fasting state and then fixed in a supine position on the operating table. Abdominal hair was trimmed, and routine disinfection was performed. A 2-2.5cm incision was made in the midline of the abdomen below the xiphoid process. The proventriculus was gently pulled outwards, and 0.05ml of 100% glacial acetic acid was dripped into the abdomen through a special glass tube, contacting the serosal surface for 1 minute. The stomach was wiped clean with a dry cotton ball, gently returned to its original position, and the skin was sutured in layers. The animals were then fed routinely. From the day after surgery, the animals were randomly assigned to groups. The treatment groups were administered the high, medium, and low doses of the traditional Chinese medicine preparation from Example 1 by gavage; the control group was administered an equal volume of physiological saline by gavage; and the positive control group was administered cimetidine by gavage. After 11 days of continuous treatment, the patient was euthanized on the 12th day. The abdomen was opened, the pylorus and cardia were ligated, and the stomach was removed and immersed in 1% formalin solution for 10 minutes. The stomach was then cut along the greater curvature, its contents were flushed, and the ulcers were examined. The ulcer index was expressed as the mean of the longest and shortest diameters of the ulcers, and statistical analysis was performed to calculate the ulcer healing percentage and assess the drug's effect on ulcer healing.

[0161] Results: The traditional Chinese medicine preparation of this invention can significantly inhibit acetic acid-induced gastric ulcers, showing a significant difference compared with the control group. The results are shown in Table 10.

[0162] Table 10 Effects on acetic acid-induced gastric ulcers in rats

[0163]

[0164] Compared with the negative control group: *:P<0.05,***P<0.001.

[0165] Example E3: Effect of the herbal preparation of the present invention on gastric emptying in mice

[0166] Dosage: (1) Negative control group: equal volume of physiological saline

[0167] (2) Positive control group: each ml contained 0.06 mg of domperidone (1.2 mg / kg);

[0168] (3) Low-dose group: each ml contains 0.16g of crude drug (3.2g / kg);

[0169] (4) Medium-dose group: Each ml contains 0.32g of raw drug (6.4g / kg);

[0170] (5) High-dose group: Each ml contains 0.64g of raw drug (12.8g / kg);

[0171] Methods: Mice weighing 20-22g (both male and female) were used. They were fasted for 12 hours before the experiment but allowed free access to water. They were randomly divided into 5 groups: a negative control group, a positive control group (Domperidone), and high, medium, and low dose groups of the traditional Chinese medicine preparation from Example 1. To avoid interference from the color of the traditional Chinese medicine itself, subcutaneous administration was used. 30 minutes after administration, 0.2ml of 0.1% methyl orange solution was administered by gavage. The mice were euthanized by dislocation 20 minutes later. The stomach was removed by abdominal dissection and placed in a small beaker. 10ml of distilled water was added. The stomach was cut open along the greater curvature, and the stomach contents were thoroughly washed into distilled water. The pH was adjusted to 6.0-6.5 with 5% sodium bicarbonate solution. The mixture was centrifuged at 2000rpm for 10 minutes. The supernatant was measured at 420nm. The instrument was zeroed with distilled water. 0.2ml of 0.1% methyl orange was added to 10ml of distilled water to determine the baseline methyl orange optical density.

[0172]

[0173] Results: Subcutaneous injection of the traditional Chinese medicine preparation of the present invention for 3 days can reduce the gastric residual rate of methyl orange, which is significantly different from the control group; the results are shown in Table 11.

[0174] Table 11 Effects on gastric emptying in mice (X±SD)

[0175]

[0176] Compared with the negative control group: **: P < 0.01, ***: P < 0.001

[0177] Example E4: Effect of the herbal preparation of the present invention on small intestinal propulsion in mice.

[0178] Dosage: (1) Negative control group: equal volume of physiological saline;

[0179] (2) Positive control group: each ml contained 0.06 mg of domperidone (1.2 mg / kg);

[0180] (3) Low-dose group: each ml contains 0.16g of raw drug (3.2g / kg);

[0181] (4) Medium-dose group: each ml contains 0.32g of raw drug (6.4g / kg);

[0182] (5) High-dose group: each ml contains 0.64g of raw drug (12.8g / kg);

[0183] Methods: Adult mice, fasted for 24 hours, were randomly divided into 5 groups (half male and half female): a negative control group, a positive control group (Domperidone), and high, medium, and low dose groups of the traditional Chinese medicine preparation from Example 1 of this invention. Mice were administered a solution containing 50% ink via gavage. Twenty minutes after administration, the mice were euthanized by cervical dislocation. The abdominal cavity was opened, the mesentery was separated, and a section of the intestine extending from the pylorus to the ileocecal junction was cut. This section was placed on cellophane, and the small intestine was gently stretched into a straight line. The length of this section was measured as the total length of the small intestine, and the distance from the pylorus to the leading edge of the ink sac was taken as the "distance the ink traveled in the intestine."

[0184]

[0185] Results: The traditional Chinese medicine preparation in Example 1 of this invention significantly increased small intestinal propulsion, showing a significant difference compared with the control group, but had no significant effect on small intestinal volume. The results are shown in Table 12.

[0186] Table 12 Effects on small intestinal propulsion in mice (X±SD)

[0187]

[0188] Compared with the negative control group: *: P < 0.05, **: P < 0.01.

[0189] Example E5: Effect of the herbal preparation of the present invention on the composition of gastric juice in rats

[0190] Dosage: (1) Negative control group: equal volume of physiological saline

[0191] (2) Positive control group: Each ml contains 24mg of Jiebai capsules (0.48g / kg)

[0192] (3) Low-dose group: Each ml contains 0.16g of crude drug (3.2g / kg)

[0193] (4) Medium dose group: Each ml contains 0.32g of crude drug (6.4g / kg)

[0194] (5) High-dose group: Each ml contains 0.64g of crude drug (12.8g / kg)

[0195] Methods: Rats weighing 180-200g were fasted for 24 hours but given free access to water. They were randomly divided into 5 groups: a negative control group, a positive control group (using Jiebai capsules), and high, medium, and low dose groups of the traditional Chinese medicine preparation from Example 1. Rats were lightly anesthetized with ether, their abdominal hair was clipped, and routine disinfection was performed. A 2.5cm incision was made below the xiphoid process along the linea alba. The stomach was carefully lifted, and the junction of the pylorus and duodenum was ligated with sutures. The test drug was immediately injected into the duodenum. After suturing the wound, the rats were returned to their cages. They were kept fasted and deprived of water post-surgery. Three hours later, the rats were euthanized by cervical dislocation. The stomach was removed, and gastric juice was collected in graduated centrifuge tubes. The tubes were centrifuged at 3000 rpm for 15 minutes, and the supernatant was collected to calculate the gastric juice volume and perform gastric juice analysis.

[0196] 1. Gastric acid determination: The pH value of the supernatant is determined by a pH meter to measure the free acid content. Take 1.0 ml of gastric juice and place it in a small beaker, add one drop of phenolphthalein indicator, and titrate with 0.01 mol / L sodium hydroxide until a pink endpoint is reached.

[0197] Total acidity (mmol / L) = (number of mL of sodium hydroxide) × 10

[0198] Total acid output (umol / L) = Total acidity × Gastric fluid volume per hour

[0199] 2. Pepsin Activity Assay: After thoroughly beating the egg white, filter it through gauze. Fill a 1mm inner diameter capillary tube with egg white and place it in 85℃ hot water to coagulate the protein. Store it in a refrigerator for later use. Take 1ml of gastric juice and put it into an Erlenmeyer flask. Add 15ml of 0.05mol / L hydrochloric acid solution and shake well. Place two protein tubes in the flask, seal the mouth of the flask, and incubate in a constant temperature water bath at 37℃ for 24h. Take out the protein tubes and measure the length (mm) of the transparent part at both ends of the protein tube with a ruler. Calculate the average value of the four values.

[0200] Pepsin activity units = average value² × 16

[0201] Results: The traditional Chinese medicine preparation of the present invention had no significant effect on gastric juice secretion, acidity and gastric enzyme activity. The results are shown in Table 13.

[0202] Table 13 Results of pepsin activity assay in rat gastric juice (X±SD)

[0203]

[0204] Compared with the negative control group: *: P<0.05.

[0205] Example E6: Anti-inflammatory and analgesic effects of the traditional Chinese medicine preparation of this invention.

[0206] 1. Anti-inflammatory effect

[0207] Dosage: (1) Negative control group: equal volume of physiological saline

[0208] (2) Positive control group: each ml contains 1.2 mg of ibuprofen (24 mg / kg)

[0209] (3) Low-dose group: Each ml contains 0.25g of crude drug (5g / kg)

[0210] (4) Medium dose group: Each ml contains 0.5g of raw drug (10g / kg)

[0211] (5) High-dose group: Each ml contains 1.0g of crude drug (20g / kg)

[0212] Methods: Male rats weighing 120-150g were randomly divided into 5 groups: a negative control group, a positive control group, and high, medium, and low dose groups of the traditional Chinese medicine preparation from Example 1. The rats were anesthetized by intraperitoneal injection of sodium pentobarbital (30mg / kg). The left and right groins of each rat were disinfected with iodine, and after removing the iodine with 75% alcohol cotton balls, a 1cm incision was made in each groin. A 40mg autoclaved cotton ball (soaked in 0.2ml of a mixture of penicillin and streptomycin, then dried) was inserted subcutaneously through the incision using forceps, and the skin was immediately sutured. From the day of surgery, the rats were administered physiological saline and the traditional Chinese medicine preparation from Example 1 of this invention via gavage for 6 consecutive days. On the 7th day, the original incision was opened, and the cotton ball along with the surrounding connective tissue was removed. The cotton ball and adipose tissue were removed, and the rats were dried in an oven at 70℃ and weighed.

[0213] Results: The traditional Chinese medicine preparation of the present invention has a significant inhibitory effect on cotton pellet granuloma in rats, and there is a significant difference compared with the control group, indicating that the traditional Chinese medicine preparation of the present invention has a significant anti-inflammatory effect. The results are shown in Table 14.

[0214] Table 14 Effects on cotton pellet granuloma formation in rats (X±SD)

[0215]

[0216] Compared with the negative control group: *: P<0.05, ***P<0.001.

[0217] 2. Analgesic effect

[0218] Dosage: (1) Negative control group: equal volume of physiological saline

[0219] (2) Positive control group: Each ml contains 1.2 mg of ibuprofen (24 mg / kg)

[0220] (3) Low-dose group: each ml contains 0.25g of crude drug (5g / kg)

[0221] (4) Medium dose group: each ml contains 0.5g of raw drug (10g / kg)

[0222] (5) High-dose group: Each ml contains 1.0g of crude drug (20g / kg)

[0223] 18-22g mice were selected. 0.5h after administration, each mouse was injected with 0.1ml / 10g of 0.6% acetic acid via intraperitoneal injection. The time of writhing and the number of writhing episodes in each mouse within 10min and 30min were recorded. Differences between groups were compared and the analgesic percentage was calculated.

[0224] Results: After oral administration of the herbal preparation of the present invention, the time for the first writhing in mice was prolonged, which was significantly different from that in the saline group (P<0.01). The number of writhing episodes within 10 min and 30 min decreased, which was significantly different from that in the saline group. This indicates that the herbal preparation of Example 1 of the present invention has a clear analgesic effect. The results are shown in Table 15.

[0225] Table 15 Analgesic Effects

[0226]

[0227] Compared with the negative control group**: P<0.01.

[0228] The above experimental results show that the traditional Chinese medicine preparation of the present invention can significantly reduce the occurrence of water immersion stress and acetic acid burning-induced gastric ulcers in rats, significantly reduce the residual rate of methyl orange in the stomach of mice, and has no significant effect on gastric juice secretion, acidity and gastric enzyme activity. It promotes small intestinal emptying and reduces the weight of cotton pellet granulomas in rats. This proves that the traditional Chinese medicine preparation of the present invention has the effects of inhibiting ulcers, reducing the residual rate of methyl orange in the stomach of mice, having no significant effect on gastric juice secretion, acidity and gastric enzyme activity, promoting small intestinal emptying, reducing the weight of cotton pellet granulomas in rats, and having significant analgesic effects.

[0229] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A traditional Chinese medicine preparation for treating functional dyspepsia, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: Pinellia ternata 200-781 parts, Coptis chinensis 50-400 parts, Scutellaria baicalensis 100-521 parts, Zingiber officinale 150-625 parts, Panax ginseng 50-313 parts, Glycyrrhiza uralensis 100-417 parts, Ziziphus jujuba 150-625 parts, Citrus aurantium 150-521 parts; Traditional Chinese medicine preparations also include pharmaceutical excipients; The traditional Chinese medicine preparation is in granule form; The pharmaceutical excipient filler is selected from maltodextrin, and the flavoring agent is selected from sucralose.

2. The traditional Chinese medicine preparation according to claim 1, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: 200-600 parts of Pinellia ternata, 50-365 parts of Coptis chinensis, 100-400 parts of Scutellaria baicalensis, 150-550 parts of dried ginger, 50-300 parts of ginseng, 100-350 parts of licorice, 150-450 parts of jujube, and 150-450 parts of Citrus aurantium.

3. The traditional Chinese medicine preparation according to claim 1, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: 250-500 parts of Pinellia ternata, 100-300 parts of Coptis chinensis, 200-350 parts of Scutellaria baicalensis, 250-400 parts of dried ginger, 100-200 parts of ginseng, 150-300 parts of licorice, 250-400 parts of jujube, and 200-350 parts of Citrus aurantium.

4. The traditional Chinese medicine preparation according to claim 1, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: 300-450 parts of Pinellia ternata, 200-300 parts of Coptis chinensis, 200-300 parts of Scutellaria baicalensis, 300-400 parts of dried ginger, 150-200 parts of ginseng, 150-250 parts of licorice, 300-400 parts of jujube, and 250-350 parts of Citrus aurantium.

5. The traditional Chinese medicine preparation according to claim 1, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: 446 parts of Pinellia ternata, 209 parts of Coptis chinensis, 298 parts of Scutellaria baicalensis, 357 parts of dried ginger, 179 parts of ginseng, 238 parts of licorice, 357 parts of jujube, and 298 parts of Citrus aurantium.

6. The method for preparing the traditional Chinese medicine preparation according to any one of claims 1-5, characterized in that, Includes the following steps: Coptis chinensis extraction steps: Coptis chinensis is extracted by reflux with ethanol, and the extract is concentrated under reduced pressure to obtain Coptis chinensis concentrate; Ginseng extraction steps: Ginseng is added to ethanol and refluxed for extraction. The extract is concentrated under reduced pressure to obtain ginseng concentrate. Water extraction steps: Add water to the remaining six ingredients and decoct. Centrifuge the extract and concentrate it to obtain a concentrated water extract. The Coptis chinensis concentrate, ginseng concentrate, and water extract concentrate are combined to prepare the traditional Chinese medicine preparation.

7. The preparation method according to claim 6, characterized in that: The water extraction step can also be performed as follows: first add the remaining six ingredients to the residue after the ginseng and berberine alcohol extraction, then add water and decoct, centrifuge the extract, concentrate it, and obtain the concentrated water extract.

8. The preparation method according to any one of claims 6 or 7, characterized in that: In the Coptis chinensis extraction step, 1-20 times the amount of ethanol is added, with an ethanol concentration of 1-80%, and the mixture is heated and refluxed for 1-3 times, each time for 0.5-6 hours, and concentrated to a relative density of 1.05-1.

16. In the ginseng extraction step, 1-20 times the amount of ethanol is added, with an ethanol concentration of 1-80%, and the mixture is heated and refluxed for 1-3 times, each time for 0.5-6 hours, and concentrated to a relative density of 1.05-1.

16. In the water extraction step, add 1-20 times the amount of water, decoct 1-3 times, each time for 0.5-6 hours, and concentrate to a relative density of 1.05-1.

16.

9. The preparation method according to claim 8, characterized in that: In the extraction step of Coptis chinensis, 8 times the amount of 70% ethanol is added to Coptis chinensis, and the mixture is heated and refluxed three times for 1 hour each time. After filtration, the extract is concentrated under reduced pressure to a relative density of 1.05-1.

16. In the ginseng extraction step, ginseng is added to 8 times the amount of 50% ethanol, and extracted by heating and reflux three times, 2 hours each time. After filtration, the extract is concentrated under reduced pressure to a relative density of 1.05-1.

16. In the water extraction step, Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and Citrus aurantium are decocted three times with 8 times the amount of water, each time for 1 hour. The extract is centrifuged and concentrated to a relative density of 1.05-1.

16. The concentrated extracts of Coptis chinensis, ginseng, and water were combined to prepare a traditional Chinese medicine preparation.

10. The preparation method according to claim 6, characterized in that: In the extraction step of Coptis chinensis, 8 times the amount of 70% ethanol is added to Coptis chinensis, and the mixture is heated and refluxed three times for 1 hour each time. After filtration, the extract is concentrated under reduced pressure to a relative density of 1.05-1.

16. In the ginseng extraction step, ginseng is added to 8 times the amount of 50% ethanol, and extracted by heating and reflux three times, 1 hour each time. After filtration, the extract is concentrated under reduced pressure to a relative density of 1.05-1.

16. In the water extraction step, Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and Citrus aurantium are first added to the residue of the ginseng and Coptis chinensis after alcohol extraction, and then 8 times the amount of water is added to decoct 3 times, 1 hour each time. The extract is centrifuged and concentrated to a relative density of 1.05-1.

16. The concentrated extracts of Coptis chinensis, ginseng, and water were combined to prepare a traditional Chinese medicine preparation.

11. The preparation method according to any one of claims 6 or 7, characterized in that: The traditional Chinese medicine preparation is in the form of granules, and the preparation method of the granules includes the following steps: (1) Add 1-16 times the amount of 10-80% ethanol to Coptis chinensis, heat and reflux to extract 1-3 times, each time for 1-3 hours, filter, recover ethanol from the filtrate under reduced pressure, and concentrate to a relative density of 1.05-1.16; (2) Add 1-16 times the amount of 10-70% ethanol to ginseng, heat and reflux to extract 1-3 times, 1-3 hours each time, filter, recover ethanol from the filtrate under reduced pressure, and concentrate to a relative density of 1.05-1.16; (3) Combine Coptis chinensis and ginseng concentrate, spray dry to obtain Coptis chinensis and ginseng spray-dried powder; (4) Prepared Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, Citrus aurantium and / or ginseng and Coptis chinensis ethanol extract residue, add 1-20 times the amount of water, decoct 1-3 times, 1-3 hours each time, centrifuge or let stand for 4-12 hours, filter, concentrate the filtrate under reduced pressure to a relative density of 1.05-1.16, spray dry the concentrate to obtain six-ingredient spray-dried powder; (5) Mix the sprayed powders of Coptis chinensis and ginseng, Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and Citrus aurantium, and granulate them to obtain granules.

12. The preparation method according to claim 11, characterized in that: In step (5), the spray-dried powders of Coptis chinensis and ginseng, Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and Citrus aurantium are mixed with an appropriate amount of maltodextrin and sucralose, and then granulated to obtain granules.

13. The preparation method according to claim 11, characterized in that: In step (1), Coptis chinensis is added with 8 times the amount of 70% ethanol, heated and refluxed three times for 1 hour each time, filtered, and the ethanol is recovered from the filtrate under reduced pressure and concentrated to a relative density of 1.05~1.

16. In step (2), ginseng is refluxed with 8 times the amount of 50% ethanol for 3 extractions, each lasting 2 hours. The mixture is then filtered, and the ethanol is recovered from the filtrate under reduced pressure and concentrated to a relative density of 1.05 to 1.

16. In step (4), Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, Citrus aurantium and / or ginseng and Coptis chinensis ethanol-extracted residue are added, 8 times the amount of water is added, and the decoction is decocted 3 times, 1 hour each time. The extract is centrifuged, and the centrifuged liquid is concentrated under reduced pressure to a relative density of 1.05-1.

16. The concentrate is spray-dried. In step (5), the spray-dried powders of Coptis chinensis and ginseng, Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and Citrus aurantium are mixed with an appropriate amount of maltodextrin and sucralose, and then granulated to obtain granules.

14. The use of the traditional Chinese medicine preparation according to any one of claims 1-4 in the preparation of a drug for treating functional dyspepsia, postprandial discomfort syndrome, gastroparesis and / or gastric ulcer.

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