Traditional Chinese medicine composition for treating functional dyspepsia combined with anxiety and depression and preparation method thereof

Abstract

The invention relates to a traditional Chinese medicine composition for treating functional dyspepsia combined with anxiety and depression and a preparation method thereof. The traditional Chinese medicine composition is prepared from the following traditional Chinese medicine raw materials in parts by weight: 200-781 parts of rhizoma pinellinae praeparata, 50-365 parts of coptis chinensis, 100-521 parts of scutellaria baicalensis, 150-625 parts of rhizoma zingiberis, 50-313 parts of ginseng, 100-417 parts of liquorice, 150-625 parts of Chinese dates and 150-521 parts of immature bitter orange. The traditional Chinese medicine composition has a good effect of treating functional dyspepsia combined with anxiety and depression, and the preparation method of the traditional Chinese medicine composition is simple and suitable for large-scale production and popularization.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of traditional Chinese medicine, and relates to a traditional Chinese medicine composition for treating functional dyspepsia combined with anxiety and depression and a preparation method thereof. BACKGROUND

[0002] Functional dyspepsia (FD) is a common functional gastrointestinal disease in the digestive system, with a global incidence of 7% to 45%. It is characterized by symptoms such as upper abdominal pain, early satiety, halitosis, nausea, vomiting, postprandial fullness, and upper abdominal burning. The symptoms of FD patients are often related to gastrointestinal motility disorders, visceral hypersensitivity, changes in gastrointestinal mucosa and immune function, changes in intestinal flora, and psychosocial factors. The various pathophysiological mechanisms are not completely independent, but interact with each other, and the abnormal intestinal-brain interaction caused by multiple factors is an important mechanism for the occurrence and development of FD.

[0003] FD is a typical disease under the biological-psychological-social medical model, and central regulation abnormalities are involved in overactive visceral sensation and gastrointestinal motility disorders. Patients often have psychological disorders such as anxiety, depression, and somatization disorder. Studies have found that the frontal cortex, somatosensory cortex, insular cortex, anterior cingulate cortex, thalamus, hippocampus, and amygdala in FD patients can have activity changes, which are related to dyspepsia symptoms, anxiety, and depression. A prospective study in Australia involving 1900 randomly selected people found that non-FD patients with more severe anxiety and depression at baseline had a higher incidence of FD after 1 year of follow-up, and FD patients with less severe anxiety and depression at baseline had significantly more severe anxiety and depression after 1 year of follow-up, suggesting that abnormal intestinal-brain interaction plays an important role in the occurrence and development of FD. A 12-year prospective cohort study also found the same phenomenon. A study in China showed that 72.4% of FD patients had anxiety, 47% had depression, and the lifetime comorbidity rate of FD and major depressive disorder was 39.1%. The coexistence of mental disorders is one of the main reasons for the ineffectiveness of conventional treatment for FD patients.

[0004] Both double-blind RCTs and retrospective studies have shown that neuromodulators can effectively treat refractory FD or FD combined with depression and anxiety. Currently, the commonly used antidepressants in clinical practice include amitriptyline, a 5-hydroxytryptamine reuptake inhibitor, escitalopram, norepinephrine, and the specific 5-hydroxytryptamine antidepressant drug mirtazapine. However, many antidepressants have problems such as long treatment period, low treatment efficiency, large side effects, the possibility of causing other psychological symptoms with long-term use, and easy recurrence, and single-targeted treatment is difficult to improve the symptoms and quality of life of patients.

[0005] FD belongs to the category of 'Pi Man' and 'Weifen Tong' in traditional Chinese medicine, and is one of the dominant diseases in traditional Chinese medicine treatment. In recent years, new progress has been made in the basic research and clinical treatment of FD by traditional Chinese medicine. The principles of invigorating the spleen and stomach, regulating qi and relieving depression, warming the middle and dispelling cold, etc. make some decoctions (such as Xiangsha Liujunzi Decoction and Chaihu Shugan Powder) provide more choices for the treatment of FD. At present, western medicine mainly treats FD by increasing gastric motility, inhibiting gastric acid, anti-depression and anti-helicobacter pylori drugs, among which the treatment of anxiety and depression is mainly through antidepressants, the first choice of which is selective 5-HT reuptake inhibitors and tricyclic antidepressants, including fluoxetine, paroxetine, venlafaxine, amitriptyline and doxepin, etc. However, such drugs have certain adverse reactions such as gastrointestinal, central nervous system and insomnia, and long-term use may cause other psychological symptoms, so the compliance is poor. At present, there is no report on the improvement of anxiety and depression in the treatment of FD by traditional Chinese medicine, so it is necessary to find traditional Chinese medicine with less toxicity, mild effect, multi-component, multi-target and multi-pathway to treat FD combined with depression. SUMMARY

[0006] In view of the above problems and deficiencies, the present application provides a traditional Chinese medicine composition, which is made of the following traditional Chinese medicine raw materials: Fashanxia, Huanglian, Huangqin, Ganjiang, Renshen, Gancao, Dazao and Zhishi, and has good treatment function for functional dyspepsia combined with anxiety and depression.

[0007] The traditional Chinese medicine composition of the present application takes Fashanxia and Weifen Tongye as the monarch, Huangqin and Huanglian as the minister, Ganjiang as the assistant, and Renshen, Zhishi, Dazao and Gancao as the adjuvant. The monarch and the minister have the effects of clearing heat and removing stagnation, and the assistant has the effect of dispersing cold. The adjuvant has the effects of warming the middle, invigorating the spleen, regulating qi, reducing swelling, dispersing mass and removing stagnation. The whole prescription has the effects of dispersing cold and clearing heat, regulating qi and stomach, reducing swelling and removing mass, and is suitable for functional dyspepsia caused by the syndrome of cold and heat mixed with fullness and distention, stomachache, nausea, vomiting, poor appetite, belching, unsmooth defecation or diarrhea, red or pale tongue, white or yellow fur, and wiry or slippery pulse.

[0008] In order to overcome the above-mentioned defects of the prior art, the present application provides a traditional Chinese medicine composition for treating functional dyspepsia combined with anxiety and depression, which is made of the following traditional Chinese medicine raw materials in the following weight parts: Fashanxia 200-781 parts, Huanglian 50-365 parts, Huangqin 100-521 parts, Ganjiang 150-625 parts, Renshen 50-313 parts, Gancao 100-417 parts, Dazao 150-625 parts and Zhishi 150-521 parts.

[0009] According to one embodiment of the present application, the Chinese medicine composition of the present application is prepared from the following Chinese medicine raw materials in the following weight parts: Baijiangxi 200-600 parts, Huanglian 50-400 parts, Huangqin 100-400 parts, Ganjiang 150-550 parts, Renshen 50-300 parts, Gancao 100-350 parts, Dazao 150-450 parts, Zhishi 150-450 parts.

[0010] Preferably, the components of the Chinese medicine composition of the present application are: Baijiangxi 250-500 parts, Huanglian 100-300 parts, Huangqin 200-350 parts, Ganjiang 250-400 parts, Renshen 100-200 parts, Gancao 150-300 parts, Dazao 250-400 parts, Zhishi 200-350 parts.

[0011] More preferably, the components of the Chinese medicine composition of the present application are: Baijiangxi 300-450 parts, Huanglian 200-300 parts, Huangqin 200-300 parts, Ganjiang 300-400 parts, Renshen 150-200 parts, Gancao 150-250 parts, Dazao 300-400 parts, Zhishi 250-350 parts.

[0012] Most preferably, the Chinese medicine composition of the present application is prepared from the following Chinese medicine raw materials in the following weight parts:

[0013] Baijiangxi 446 parts, Huanglian 209 parts, Huangqin 298 parts, Ganjiang 357 parts, Renshen 179 parts, Gancao 238 parts, Dazao 357 parts, Zhishi 298 parts.

[0014] According to one embodiment of the present application, the Chinese medicine composition of the present application is in the form of a pharmaceutical preparation, and the pharmaceutical preparation can further include a pharmaceutical excipient as needed.

[0015] According to one embodiment of the present application, the pharmaceutical preparation is at least one selected from the following forms: tablets, capsules, buccal tablets, granules, pills, powders, pills, suspensions, solutions, injections, suppositories, sprays, drops, dripping pills, patches, preferably granules or capsules.

[0016] The present application further provides a preparation method of the Chinese medicine composition, comprising the following steps:

[0017] taking Baijiangxi, Huanglian, Huangqin, Ganjiang, Renshen, Gancao, Dazao and Zhishi as eight kinds of Chinese medicinal materials,

[0018] Huanglian preparation step: Huanglian is added with ethanol for reflux extraction, and the extract is concentrated under reduced pressure;

[0019] Renshen preparation step: Renshen is added with ethanol for reflux extraction, and the extract is concentrated under reduced pressure;

[0020] Water extraction step: the remaining six Chinese herbal medicines are decocted with water, the extract is centrifuged and concentrated to obtain a water extraction concentrate;

[0021] The Huanglian concentrate, the Renshen concentrate and the water extraction concentrate are combined to prepare a traditional Chinese medicine composition.

[0022] According to a further embodiment, the remaining six Chinese herbal medicines are first added to the residues after alcohol extraction of Renshen and Huanglian, and then decocted with water, the extract is centrifuged and concentrated to obtain a water extraction concentrate;

[0023] In a preferred embodiment, in the Huanglian preparation step of the preparation method, 1-20 times of ethanol is added, the ethanol concentration is 1-80%, and the extraction is performed by heating and refluxing for 1-3 times, each time for 0.5-6 h, and the extract is concentrated to a relative density of 1.05-1.18; in the Renshen preparation step, 1-20 times of ethanol is added, the ethanol concentration is 1-80%, and the extraction is performed by heating and refluxing for 1-3 times, each time for 0.5-6 h, and the extract is concentrated to a relative density of 1.05-1.18; in the water extraction step, 1-20 times of water is added, and the decoction is performed for 1-3 times, each time for 0.5-6 h, and the extract is concentrated to a relative density of 1.05-1.18;

[0024] More preferably, in the Huanglian preparation step, 8 times of 70% ethanol is added to Huanglian, and the extraction is performed by heating and refluxing for 3 times, each time for 1 h, the extract is filtered, and the extract is concentrated under reduced pressure to a relative density of 1.05-1.18; in the Renshen preparation step, 8 times of 50% ethanol is added to Renshen, and the extraction is performed by heating and refluxing for 3 times, each time for 1 h, the extract is filtered, and the extract is concentrated under reduced pressure to a relative density of 1.05-1.18; in the water extraction step, Fabanxia, Ganjiang, Huangqi, Dazao, Gancao, Zhishi or the residues after alcohol extraction of Renshen and Huanglian are added, 8 times of water is added, and the decoction is performed for 3 times, each time for 1 h, the extract is centrifuged and concentrated to a relative density of 1.05-1.18; the Huanglian concentrate, the Renshen concentrate and the water extraction concentrate are combined to prepare a traditional Chinese medicine composition.

[0025] According to an embodiment of the present application, the traditional Chinese medicine composition of the present application is a granule, and the preparation method of the granule comprises the following steps:

[0026] (1) Huanglian is added with 1-16 times of 10-80% ethanol, and the extraction is performed by heating and refluxing for 1-3 times, each time for 1-3 hours, the extract is filtered, the ethanol in the filtrate is recovered under reduced pressure, and the extract is concentrated to a relative density of 1.05-1.18;

[0027] (2) Renshen is added with 1-16 times of 10-70% ethanol, and the extraction is performed by heating and refluxing for 1-3 times, each time for 1-3 hours, the extract is filtered, the ethanol in the filtrate is recovered under reduced pressure, and the extract is concentrated to a relative density of 1.05-1.18;

[0028] (3) combine the concentrated liquid of Coptis chinensis and Panax ginseng, and spray dry to obtain Coptis chinensis and Panax ginseng spray dry powder;

[0029] (4) Pinellia ternata, Zingiber officinale, Scrophularia ningpoensis, Fructus Jujubae, Glycyrrhiza uralensis, and Citrus aurantium are added with 1-20 times of water, decocted 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 1.05-1.18, and the concentrated liquid is spray dried to obtain six-ingredient spray dry powder;

[0030] (5) Coptis chinensis and Panax ginseng spray dry powder and six-ingredient spray dry powder are mixed with appropriate amount of dextrin and sucralose to granulate to obtain granules.

[0031] According to one embodiment, in the above step (4), the residues of Coptis chinensis and Panax ginseng after alcohol extraction are added to Pinellia ternata, Zingiber officinale, Scrophularia ningpoensis, Fructus Jujubae, Glycyrrhiza uralensis, and Citrus aurantium, and 1-20 times of water is added, decocted 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 1.05-1.18, and the concentrated liquid is spray dried to obtain six-ingredient spray dry powder.

[0032] Preferably, in the above step (1), Coptis chinensis is added with 8 times of 70% ethanol, heated to reflux and extracted for 3 times, each time for 1 hour, filtered, the ethanol in the filtrate is recovered under reduced pressure, and the concentrated liquid is concentrated to a relative density of 1.05-1.18.

[0033] Preferably, in the above step (2), Panax ginseng is added with 8 times of 50% ethanol, heated to reflux and extracted for 3 times, each time for 1 hour, filtered, the ethanol in the filtrate is recovered under reduced pressure, and the concentrated liquid is concentrated to a relative density of 1.05-1.18.

[0034] Preferably, in the above step (3), the concentrated liquid of Coptis chinensis and Panax ginseng is combined and spray dried.

[0035] Preferably, in the above step (4), Pinellia ternata, Zingiber officinale, Scrophularia ningpoensis, Fructus Jujubae, Glycyrrhiza uralensis, and Citrus aurantium are added with 8 times of water, decocted for 3 times, each time for 1 hour, the extract is centrifuged, the centrifugal liquid is concentrated under reduced pressure to a relative density of 1.05-1.18, and the concentrated liquid is spray dried.

[0036] Preferably, in the above step (5), Coptis chinensis and Panax ginseng spray dry powder and six-ingredient spray dry powder are mixed with appropriate amount of dextrin and sucralose to granulate to obtain granules.

[0037] The application further provides use of the traditional Chinese medicine composition in preparation of functional dyspepsia, depression, anxiety, functional dyspepsia combined with anxiety and depression, promotion of gastrointestinal motility, gastric emptying, gastroparesis, gastric ulcer, anti-inflammatory, or analgesic drugs.

[0038] The following is the explanation and description of the nomenclature of the present application: The raw materials involved in the traditional Chinese medicine composition for treating functional dyspepsia, depression, anxiety, functional dyspepsia combined with anxiety and depression, promoting gastrointestinal motility, gastric emptying, gastroparesis, gastric ulcer, anti-inflammatory or analgesia in the present application are as follows:

[0039] Fahai is the dry tuber of Pinellia ternata (Thunb.) Breit. of Araceae. It is pungent and warm, and belongs to spleen, stomach and lung channels. It is used for phlegm cough and asthma, phlegm-dampness dizziness, wind-phlegm dizziness, phlegm cold headache.

[0040] Huanglian is the dry rhizome of Coptis chinensis Franch. of Ranunculaceae. It is bitter and cold, and belongs to heart, spleen, stomach, liver, gallbladder and large intestine channels. It is used for damp-heat distention, vomiting and acid regurgitation, diarrhea, jaundice, high fever with coma, heart fire, restlessness, insomnia, palpitation, blood heat, hematemesis, eye redness, toothache, diabetes, carbuncle and sore.

[0041] Huangqin is the dry root of Scutellaria baicalensis Georgi of Labiatae. It is bitter and cold, and belongs to lung, gallbladder, spleen, large intestine and small intestine channels. It is used for damp-warm, summer dampness, chest stuffiness and vomiting, damp-heat distention, diarrhea, jaundice, lung heat cough, high fever with thirst, blood heat hematemesis, carbuncle and sore, and unstable fetus.

[0042] Ganjiang is the dry rhizome of Zingiber officinale Rosc. of Zingiberaceae. It is pungent and hot, and belongs to spleen, stomach, kidney, heart and lung channels. It is used for cold pain in the abdomen, vomiting and diarrhea, cold limbs and weak pulse, cold-dampness and cough.

[0043] Renshen is the dry root and rhizome of Panax ginseng C.A.Mey. of Araliaceae. It is sweet and bitter, and slightly warm. It belongs to spleen, lung, heart and kidney channels. It is used for body weakness, cold limbs and weak pulse, spleen deficiency with poor appetite, lung deficiency with cough, fluid deficiency with thirst, internal heat with diabetes, deficiency of qi and blood, long-term illness with emaciation, palpitation and insomnia, impotence and cold uterus.

[0044] Gancao is the dry root and rhizome of Glycyrrhiza uralensis Fisch. of Leguminosae. It is sweet and neutral. It belongs to heart, lung, spleen and stomach channels. It is used for spleen and stomach weakness, lethargy, palpitation and shortness of breath, cough with much phlegm, abdominal and limb pain, carbuncle and sore, and relieving drug toxicity and virulence.

[0045] Dazao is the dry mature fruit of Ziziphus jujuba Mill. of Rhamnaceae. It is sweet and warm, and belongs to spleen, stomach and heart channels. It is used for spleen deficiency with poor appetite, lethargy, diarrhea, and women with restlessness.

[0046] Citrus aurantium L. and its cultivated varieties. Bitter, pungent, sour, and slightly cold. It belongs to the spleen and stomach meridians. It is used for accumulation and stagnation, distention and pain, diarrhea, constipation, phlegm, chest pain, and organ prolapse.

[0047] The traditional Chinese medicine composition / traditional Chinese medicine preparation of the present application is preferably in the form of a unit dose pharmaceutical preparation. The oral preparation is selected from one of a capsule, a tablet, a dripping pill, a granule, a concentrated pill, an oral liquid, and a mixture. The injection is selected from one of an injection liquid, a freeze-dried powder injection, and an aqueous injection.

[0048] The pharmaceutical composition of the present application can contain common excipients such as binders, fillers, diluents, tabletting agents, lubricants, disintegrants, colorants, flavorings, and wetting agents in the preparation for oral administration, and the tablets can be coated if necessary.

[0049] Suitable fillers include cellulose, mannitol, lactose, and other similar fillers. Suitable disintegrants include starch, polyvinylpyrrolidone, and starch derivatives such as sodium starch glycolate. Suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium dodecyl sulfate.

[0050] The pharmaceutical composition of the present application can be prepared into a solid oral composition by mixing, filling, tabletting, and the like common methods. Repeated mixing can be performed to distribute the active substance throughout those compositions using a large amount of fillers.

[0051] The form of the oral liquid preparation can be, for example, an aqueous or oily suspension, a solution, an emulsion, a syrup, or an elixir, or can be a dry product that can be reconstituted with water or other suitable carriers before use. Such a liquid preparation can contain conventional additives such as suspending agents, for example, sorbitol, syrup, methyl cellulose, gelatin, hydroxyethyl cellulose, carboxymethyl cellulose, aluminum stearate gel, or hydrogenated edible fat; emulsifying agents, for example, lecithin, sorbitan monooleate, or acacia; non-aqueous carriers (which can include edible oils) such as almond oil, fractionated coconut oil, oily esters of esters such as glycerol, propylene glycol, or ethanol; preservatives such as p-hydroxybenzoic acid esters or propyl p-hydroxybenzoate or sorbic acid, and if necessary, conventional flavorings or colorings.

[0052] For injection, the prepared liquid unit dosage form contains the active substance of the present application and a sterile carrier. Depending on the carrier and the concentration, the compound can be suspended or dissolved. The preparation of the solution is usually by dissolving the active substance in a carrier, sterilizing by filtration before filling into a suitable vial or ampoule, and then sealing. Excipients such as a local anesthetic, a preservative and a buffer can also be dissolved in the carrier. In order to improve its stability, the composition can be frozen after filling into a vial, and water is removed under vacuum.

[0053] The pharmaceutical composition of the present application, when prepared into a medicament, can optionally add a suitable pharmaceutically acceptable carrier selected from the group consisting of mannitol, sorbitol, sodium pyrosulfite, sodium bisulfite, sodium thiosulfate, cysteine hydrochloride, mercaptoacetic acid, methionine, vitamin C, disodium EDTA, calcium sodium EDTA, monovalent alkali metal carbonate, acetate, phosphate or aqueous solution thereof, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acid, 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, Tween 80, agar, calcium carbonate, calcium bicarbonate, surfactants, polyethylene glycol, dextrin, cyclodextrin, beta-cyclodextrin, phospholipid material, kaolin, talc, calcium stearate, magnesium stearate, etc.

[0054] The flavoring agent is to improve the taste of the granules, and the sweetener is usually sweetener, aspartame, sucralose, etc.

[0055] Obviously, according to the above content of the present application, according to the ordinary technical knowledge and common practice in the art, other various forms of modification, replacement or change can be made without departing from the above basic technical idea of the present application.

[0056] The beneficial technical effects of the present application are:

[0057] 1. The traditional Chinese medicine composition in the present application is composed of eight medicines of Fashi Xia, Huanglian, Huangqi, Ganjiang, Renshen, Gancao, Dazao and Zhishi. Through pharmacological research, it is found that the traditional Chinese medicine composition mainly plays an intervention role on FD through three modules of NOS, 5-HT and immunity / inflammation, and can improve anxiety and depression. Furthermore, through FD animal model research, it is found that the traditional Chinese medicine composition can restore the abnormally secreted brain-gut peptide to normal level.

[0058] 2. The present application verifies that the traditional Chinese medicine composition has the effect of treating functional dyspepsia combined with anxiety and depression.

[0059] 3. Animal experiments of this invention verify that the herbal composition 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 composition 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 composition 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.

[0060] 4. The experimental results of this invention show that the traditional Chinese medicine composition 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, and has analgesic and anti-inflammatory effects. Attached Figure Description

[0061] Figure 1 : Figure 1 A represents the MTL content in rats of each group after drug administration. n = 6); Figure 1 B represents the GAS content in rats of each group after drug administration. n = 6);

[0062] Figure 2 : Figure 2 A represents the serum VIP content of rats in each group after drug administration. n = 6); Figure 2 B represents the serum CGRP content of rats in each group after drug administration. n = 6);

[0063] Figure 3 : Figure 3 A represents the expression of 5-HT in rat gastric antrum tissue. n = 6); Figure 3 B represents the expression of 5-HT in rat hypothalamic tissue. n = 6);

[0064] Figure 4 The effects of the herbal composition of this invention on 5-HT staining of the gastric antrum and hypothalamus of rats in various groups;

[0065] Figure 5 AMS content in rats of each group after drug administration ( n = 6);

[0066] Figure 6 NOS activity in rats of different groups after drug administration ( n = 6);

[0067] Figure 7 Western blot was used to detect the expression of Akt and p-Akt proteins in the gastric tissue of rats in each group.

[0068] Figure 8 Figure 8 A is the influence of the expression of Akt protein in the stomach tissue of rats in each group after administration; Figure 8 B is the influence of the expression of p-Akt protein in the stomach tissue of rats in each group after administration. DETAILED DESCRIPTION

[0069] The present application is further illustrated by the following examples, but is not limited to the following examples.

[0070] Example 1

[0071] Method: Pinellia 446g, Coptis 209g, Scutellaria 298g, Dried Ginger 357g, Ginseng 179g, Licorice 238g, Jujube 357g, Citrus aurantium 298g

[0072] According to the above weight, respectively take Pinellia, Coptis, Scutellaria, Dried Ginger, Ginseng, Licorice, Jujube, and Citrus aurantium, 8 kinds of traditional Chinese medicinal materials, add 8 times the amount of 70% ethanol to Coptis, heat reflux extraction for 3 times, 1h each time, and reduce pressure concentration of the extract, and concentrate to relative density 1.05-1.18; add 8 times the amount of 50% ethanol to Ginseng, heat reflux extraction for 3 times, 1h each time, and reduce pressure concentration of the extract, and concentrate to relative density 1.05-1.18, and add 8 times the amount of water to the residue of Ginseng and Coptis after alcohol extraction and the remaining six kinds, decoct for 3 times, 1h each time, and centrifugal and concentrate the extract, and concentrate to relative density 1.05-1.18; combine the concentrated solution of Coptis, the concentrated solution of Ginseng, and the water extraction concentrated solution, and the traditional Chinese medicinal composition is obtained.

[0073] Example 2

[0074] Method: Pinellia 200g, Coptis 50g, Scutellaria 100g, Dried Ginger 150g, Ginseng 50g, Licorice 100g, Jujube 150g, Citrus aurantium 150g

[0075] According to the above weight, respectively take Pinellia, Coptis, Scutellaria, Dried Ginger, Ginseng, Licorice, Jujube, and Citrus aurantium, 8 kinds of traditional Chinese medicinal materials, add 8 times the amount of 70% ethanol to Coptis, heat reflux extraction for 3 times, 1h each time, and reduce pressure concentration of the extract, and concentrate to relative density 1.05-1.18; add 8 times the amount of 50% ethanol to Ginseng, heat reflux extraction for 3 times, 1h each time, and reduce pressure concentration of the extract, and concentrate to relative density 1.05-1.18, and add 8 times the amount of water to the residue of Ginseng and Coptis after alcohol extraction and the remaining six kinds, decoct for 3 times, 1h each time, and centrifugal and concentrate the extract, and concentrate to relative density 1.05-1.18; combine the concentrated solution of Coptis, the concentrated solution of Ginseng, and the water extraction concentrated solution, and the traditional Chinese medicinal composition is obtained.

[0076] Example 3

[0077] ​Rhizoma pinelliae 600g, Rhizoma coptidis 400g, Radix scophulariae 400g, Radix zingiberis 550g, Radix ginseng 300g, Radix glycyrrhizae 350g, Fructus jujubae 450g, Fructus aurantii immaturus 450g

[0078] Rhizoma pinelliae, Rhizoma coptidis, Radix scophulariae, Radix zingiberis, Radix ginseng, Radix glycyrrhizae, Fructus jujubae, Fructus aurantii immaturus were taken according to the above weight, Rhizoma coptidis was added with 12 times of 80% ethanol, heated to reflux and extracted for 3 times, each for 3h, the extract was concentrated under reduced pressure to relative density 1.05-1.18; Radix ginseng was added with 12 times of 75% ethanol, heated to reflux and extracted for 3 times, each for 1h, the extract was concentrated under reduced pressure to relative density 1.05-1.18, the residues of Radix ginseng and Rhizoma coptidis after alcohol extraction and the remaining six were added with 12 times of water, decocted for 3 times, each for 1h, the extract was centrifuged and concentrated to relative density 1.05-1.18; the concentrated solution of Rhizoma coptidis, Radix ginseng and water extraction were combined, to obtain the traditional Chinese medicine composition.

[0079] Example 4

[0080] Rhizoma pinelliae 250g, Rhizoma coptidis 100g, Radix scophulariae 200g, Radix zingiberis 250g, Radix ginseng 100g, Radix glycyrrhizae 150g, Fructus jujubae 250g, Fructus aurantii immaturus 200g;

[0081] Rhizoma pinelliae, Rhizoma coptidis, Radix scophulariae, Radix zingiberis, Radix ginseng, Radix glycyrrhizae, Fructus jujubae, Fructus aurantii immaturus were taken according to the above weight, Rhizoma coptidis was added with 10 times of 70% ethanol, heated to reflux and extracted for 2 times, each for 1h, the extract was concentrated under reduced pressure to relative density 1.05-1.18; Radix ginseng was added with 10 times of 50% ethanol, heated to reflux and extracted for 2 times, each for 1h, the extract was concentrated under reduced pressure to relative density 1.05-1.18, the residues of Radix ginseng and Rhizoma coptidis after alcohol extraction and the remaining six were added with 10 times of water, decocted for 2 times, each for 1h, the extract was centrifuged and concentrated to relative density 1.05-1.18; the concentrated solution of Rhizoma coptidis, Radix ginseng and water extraction were combined, to obtain the traditional Chinese medicine composition.

[0082] Example 5

[0083] Rhizoma pinelliae 500g, Rhizoma coptidis 300g, Radix scophulariae 350g, Radix zingiberis 400g, Radix ginseng 200g, Radix glycyrrhizae 300g, Fructus jujubae 400g, Fructus aurantii immaturus 350g;

[0084] The following eight kinds of Chinese medicinal materials, i.e., Pinelliae Rhizoma Praeparatum, Coptidis Rhizoma, Scutellariae Radix, Zingiberis Rhizoma, Ginseng Radix et Rhizoma, Glycyrrhizae Radix, Jujubae Fructus, and Aurantii Fructus Immaturus, are taken according to the above-mentioned weights, respectively. Coptidis Rhizoma is added with 6 times of 40% ethanol, and heated to reflux for extraction for 1 time, each time for 3 hours. The extract is reduced in pressure and concentrated to a relative density of 1.05-1.18. Ginseng Radix et Rhizoma is added with 6 times of 40% ethanol, and heated to reflux for extraction for 1 time, each time for 3 hours. The extract is reduced in pressure and concentrated to a relative density of 1.05-1.18. The residues of Ginseng Radix et Rhizoma and Coptidis Rhizoma after alcohol extraction and the remaining six kinds of Chinese medicinal materials are added with 8 times of water, and decocted for 1 time, each time for 3 hours. The extract is centrifuged and concentrated to a relative density of 1.05-1.18. The concentrated solution of Coptidis Rhizoma, the concentrated solution of Ginseng Radix et Rhizoma and the water-extracted concentrated solution are combined, thereby obtaining the Chinese medicinal composition.

[0085] Example 6: Capsule

[0086] Pinelliae Rhizoma Praeparatum 781g, Coptidis Rhizoma 365g, Scutellariae Radix 521g, Zingiberis Rhizoma 625g, Ginseng Radix et Rhizoma 313g, Glycyrrhizae Radix 417g, Jujubae Fructus 625g, Aurantii Fructus Immaturus 521g

[0087] 1000 capsules are prepared. (1) Coptidis Rhizoma: 8 times of 70% ethanol is added, heated to reflux for extraction for 3 times, each time for 1 hour, filtered, the filtrates are combined, ethanol is recovered under reduced pressure, and the concentrated solution is spray-dried into fine powder, which is reserved for later use. (2) Ginseng Radix et Rhizoma: 8 times of 50% ethanol is added, heated to reflux for extraction for 3 times, each time for 2 hours, filtered, the filtrates are combined, ethanol is recovered under reduced pressure, and the concentrated solution is spray-dried into fine powder, which is reserved for later use. (3) Pinelliae Rhizoma Praeparatum, Zingiberis Rhizoma, Scutellariae Radix, Jujubae Fructus, Glycyrrhizae Radix, Aurantii Fructus Immaturus and the residues of Ginseng Radix et Rhizoma and Coptidis Rhizoma after alcohol extraction are added with 8 times of water, decocted for 3 times, each time for 1 hour, and left to settle for 24 hours. The filtrates are combined, concentrated under reduced pressure to a relative density of 1.05-1.18, and the concentrated solution is spray-dried into fine powder, which is reserved for later use. The dry fine powders of (1), (2) and (3) are combined, mixed, granulated with 50% ethanol, dried at 60°C, and granulated, and then filled into 0.5g / capsule, thereby obtaining the product.

[0088] Example 7: Granules

[0089] Pinelliae Rhizoma Praeparatum 446g, Coptidis Rhizoma 209g, Scutellariae Radix 298g, Zingiberis Rhizoma 357g, Ginseng Radix et Rhizoma 179g, Glycyrrhizae Radix 238g, Jujubae Fructus 357g, Aurantii Fructus Immaturus 298g

[0090] Rhizoma Coptidis was extracted with 8 times of 70% ethanol by heating reflux for 3 times, 1 hour each time, and filtered. The filtrate was concentrated by reducing pressure to recover ethanol, and concentrated to a relative density of 1.05-1.18. The concentrated solution was prepared for use. Ginseng was extracted with 8 times of 50% ethanol by heating reflux for 3 times, 1 hour each time, and filtered. The filtrate was concentrated by reducing pressure to recover ethanol, and concentrated to a relative density of 1.05-1.18. The concentrated solution was prepared for use. The concentrated solutions of Rhizoma Coptidis and Ginseng were combined and spray dried. Pinelliae, Zingiberis, Scrophulariae, Radicis Paeoniae, Glycyrrhizae, Citri Sarcodocchi, or the residues after ethanol extraction of Rhizoma Coptidis and Ginseng were added with 8 times of water, and decocted for 3 times, 1 hour each time. The extract was centrifuged, filtered, and concentrated by reducing pressure to a relative density of 1.05-1.18. The concentrated solution was spray dried and prepared for use.

[0091] Rhizoma Coptidis and Ginseng were mixed with a suitable amount of dextrin and a suitable amount of sucralose to prepare 1000 g of granules.

[0092] Example 8: Selection of spray drying process

[0093] A comparative study was conducted on the spray drying of Rhizoma Coptidis and Ginseng alone and the spray drying of Rhizoma Coptidis and Ginseng mixture to determine the optimal experimental process of the spray drying of Rhizoma Coptidis and Ginseng mixture. The test data are shown in Table 1 below.

[0094] Table 1: Experimental data of spray drying of Rhizoma Coptidis and Ginseng alone and mixture

[0095]

[0096]

[0097] As can be seen from Table 1, there are certain differences in the powder yield and the transfer rate of berberine hydrochloride between the spray drying of Rhizoma Coptidis and Ginseng alone and the spray drying of Rhizoma Coptidis and Ginseng mixture. The powder yield of the spray drying of Rhizoma Coptidis and Ginseng alone is between 16.71% and 16.92%, and the transfer rate of berberine hydrochloride is between 65.38% and 65.51%.

[0098] The powder yield of the spray drying of Rhizoma Coptidis and Ginseng mixture is between 17.12% and 17.58%, and the transfer rate of berberine hydrochloride is between 68.69% and 68.27%. Moreover, the spray drying of Rhizoma Coptidis and Ginseng mixture is simpler than the spray drying of Rhizoma Coptidis and Ginseng alone, and the process is simplified. Therefore, the spray drying process of the concentrated solution of Rhizoma Coptidis and Ginseng mixture is the most reasonable, and thus, the spray drying of the mixture in Example 7 is the most reasonable.

[0099] Example 9: Selection of types of excipients

[0100] The intermediate powder of the product is extremely easy to absorb moisture, and in combination with the commonly used excipients in the literature, two kinds of excipients, dextrin and starch, are selected in the screening of excipients, and are evaluated from the aspects of granule solubility and granule yield. The ratio of drug powder and excipient is 1:1 in the screening process, so as to observe and evaluate the influence of excipients on the granules of the product. The specific test results are shown in Table 2 below.

[0101] Table 2 Analysis table of excipient type screening

[0102]

[0103] Dextrin is a white amorphous powder, odorless, slightly sweet, easily soluble in boiling water, slowly soluble in cold water, safe and non-toxic, low price, easy to get, relatively stable in high temperature and high humidity environment. As can be seen from Table 2, dextrin as a filler of the product has good adhesion, and the granule yield and granule solubility are better than starch, so dextrin is selected as the filler of the product.

[0104] Effect example E1

[0105] Experimental method: 10-day-old suckling rats were randomly divided into two groups, normal group (8) and model group (14). The normal group was given 2% sucrose solution by gavage at 9:00 am every day, 0.2 mL per mouse, for 6 consecutive days. The model group was given 0.1% iodoacetamide 2% sucrose solution by gavage at 9:00 am every day, 0.2 mL per mouse, for 6 consecutive days. Then they were normally raised, and the feeding conditions were unchanged. The rats were raised to 3 weeks old, weaned (stop breastfeeding), and the mother rats were removed. The rats were divided into cages, 3 rats per cage, and fed with conventional feed. The rats were raised to 6 weeks old, and the normal group was normally raised; the model group rats ate every other day for 14 consecutive days. The second day after the modeling was completed, the modeling rats were randomly divided into model group and administration group, and gavage administration was performed at 9:00 am. The administration group was prepared with 0.9 g / kg dose of the traditional Chinese medicine composition solution in example 1 of the present application for gavage, and the normal group and the model group were given the same volume of normal saline by gavage, and the administration was continued for 4 weeks. During the administration period, the rats in each group were fed with ordinary feed and free drinking of pure water, and the body weight of the rats was measured once a day, and the gavage administration amount was adjusted according to the change of body weight. After the last administration, the rats were fasted for 24 h, anesthetized by intraperitoneal injection of 3% sodium pentobarbital (100 mg / kg), and blood was taken from the abdominal aorta, and after standing for 30 min, centrifugation was performed at 4°C and 4500 rpm for 10 min, and the supernatant was collected and stored in a-80°C refrigerator. The rats were sacrificed by cervical dislocation, the cardia and pylorus of the stomach were ligated on the clean bench, the whole stomach was taken out, cut open along the greater curvature, and the stomach contents were washed with distilled water, and the volume was adjusted to 20 mL, and stored in a-80°C refrigerator for use. The antral circular muscle strip 0.5 cm away from the pylorus was taken out, the rat brain was cut, the rat cranial cavity was opened on ice, the hippocampus and hypothalamus tissues were taken out, and fixed in 4% paraformaldehyde solution.

[0106] 1. Determination of rat serum motilin (MTL) and gastrin (GAS) contents

[0107] The results of rat serum motilin (MTL) content are shown in Table 3 and Figure 1 The results of gastrin (GAS) content are shown in Table 3 and Figure 1 B. After administration of the solution of the pharmaceutical composition of Example 1 of the present application, the contents of MTL and GAS in the serum of the rats of the administration group were higher than those of the model group, and there were significant differences (P < 0.01). Compared with the normal group, the content of GAS in the serum of the rats of the model group was significantly reduced, and there was a significant difference (P < 0.01).

[0108] Table 3 Comparison of rat serum MTL and GAS contents n = 6

[0109]

[0110] Note: Compared with the normal group, ** : P < 0.01. Compared with the model group, # : P < 0.05.

[0111] 2. Determination of rat serum vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) contents

[0112] The results of rat serum vasoactive intestinal peptide (VIP) content are shown in Table 4 and Figure 2 A. The results of calcitonin gene-related peptide (CGRP) content are shown in Table 4 and Figure 2 B. VIP and CGRP are the main inhibitory neurotransmitters of the gastrointestinal tract. VIP has the effects of inhibiting contraction of digestive tract smooth muscle, slowing gastric emptying, inhibiting small intestinal movement and secretion of water and electrolytes, and inhibiting contraction of the gallbladder to regulate intragastric pressure. Serum CGRP is an effective peptide vasodilator and can play a role in the transmission of pain. Abnormal increase of CGRP in the body of FD patients can increase pain-related nociceptive transmission, thereby causing visceral hypersensitivity. As can be seen from Figure 2 A and Figure 2 B, the contents of VIP and CGRP in the serum of the rats of the model group were higher than those of the normal group and the administration group, and there were significant differences (P < 0.05).

[0113] Table 4 Comparison of rat serum VIP and CGRP contents n = 6

[0114]

[0115] Note: Compared with the normal group, * : P < 0.05; Compared with the model group, # : P < 0.05.

[0116] 3. Expression of 5-HT in hypothalamus and antrum of rats

[0117] The expression of 5-HT in the antrum of rats in each group was detected by IHC method, and the results are shown in Table 5 and Figure 3 A, and the IHC staining is shown in Figure 4 The expression of 5-HT in the hypothalamus of rats in each group was detected by IHC method, and the results are shown in Table 5 and Figure 3 B, and the IHC staining is shown in Figure 4 It can be seen from Table 5 that the expression of 5-HT in the antrum and hypothalamus of rats in the administration group (0.9 g / kg of the composition of Example 1 of the present application) was increased to different degrees, especially the expression of 5-HT in the hypothalamus had a significant difference (P<0.01) compared with the model group, and the expression in the antrum had a significant difference (P<0.05) compared with the model group, and the expression in the model group had no significant difference compared with the normal group.

[0118] Table 5 Expression of 5-HT in the antrum and hypothalamus of rats in each group n=6

[0119]

[0120] Note: compared with the model group, # : P<0.05, ## : P<0.01.

[0121] 4. Determination of the content of serum amylase (AMS) of rats

[0122] The content of serum amylase (AMS) of rats in each group before and after administration was determined by using a kit, and after data analysis, it was found that the content of AMS in the model group was significantly decreased (P<0.01) after the model was established, indicating that the model was successfully established. After administration, there was no significant difference in the content of AMS between the normal group and the model group, which might be due to the self-healing of the rats in the model group during the one-month administration, so there was no significant difference. Compared with the normal group, the content of AMS in the administration group (0.9 g / kg of the composition of Example 1 of the present application) was significantly increased (P<0.05); compared with the model group, the content of AMS in the administration group was significantly increased (P<0.01), which had a significant difference. The comparison of the content of AMS of rats in each group before and after administration is shown in Table 6 and Figure 5 .

[0123] Table 6 Comparison of the content of serum AMS of rats in each group n=6

[0124]

[0125]

[0126] 5. Determination of the activity of nitric oxide synthase (NOS) in the stomach tissue of rats

[0127] The stomach tissue of rats was taken for tissue homogenate, which was prepared into 10% stomach tissue homogenate solution with normal saline. The activity of nitric oxide synthase (NOS) in the stomach tissue of rats was determined by chemical method. The determination results are shown in Table 7 and Figure 6 . The results show that, compared with the model group, the NOS activity in the stomach tissue of rats in the normal group and the administration group (the traditional Chinese medicine composition (0.9 g / kg) in Example 1 of the present application) has a significant difference (P < 0.05). NOS catalyzes L-Arg to form NO. At present, the mainstream view considers that the increase of NO will inhibit the gastrointestinal motility, so NOS is a negative regulation.

[0128] Table 7 Comparison of the NOS activity in the stomach tissue of rats in each group n = 6

[0129]

[0130] Note: * compared with the normal group, * : P < 0.05; # compared with the model group, # : P < 0.05.

[0131] 6. Determination of the expression level of Akt and p-Akt in the stomach tissue of FD rats

[0132] The expression level of Akt and p-Akt in the stomach tissue of FD rats was determined by Western Blot detection method, and the results are shown in Figure 7 and Figure 8 A and Figure 8 B. The Western Blot detection results show that the average Akt gray ratio values of the normal group, the model group and the administration group are 0.66, 0.73 and 0.66 respectively, and the average p-Akt gray ratio values are 0.79, 0.92 and 0.73 respectively. The expression amount of p-Akt in the model group is higher than that in the administration group, and the expression amount of Akt is also increased. As shown in Figure 7 and Figure 8 A and Figure 8 B, the protein bands of Akt and p-Akt in the model group are wider and darker than those in the normal group and the administration group.

[0133] The therapeutic effect of the traditional Chinese medicine composition in Example 1 of the present application on FD can be related to the PI3K-Akt / NOS signal pathway, the expression of Akt and p-Akt on the pathway is inhibited, thereby the expression of NOS is inhibited, the amount of inhibitory neurotransmitter NO is reduced, and NO plays an important role in stimulating gastrointestinal secretion and relaxing gastrointestinal smooth muscle, thereby the purpose of treating FD is achieved. Meanwhile, the traditional Chinese medicine composition can promote the secretion of AMS, thereby the digestive and metabolic function of the FD rat is improved, and the therapeutic effect on FD is achieved.

[0134] Effect Example E2 Anti-gastric ulcer effect of the traditional Chinese medicine composition of the present application on rats

[0135] Test animals: Wistar rats: provided by the Animal Breeding Farm of the Chinese Academy of Medical Sciences, qualification certificate number: medical movement word No. 01-3008; KM mice: provided by the Animal Breeding Farm of the Chinese Academy of Medical Sciences, qualification certificate number: medical movement word No. 01-3001.

[0136] Dose: (1) Control group: equal volume of normal saline.

[0137] (2) Positive control group: 4 mg (80 mg / kg) of cimetidine per ml;

[0138] (3) Low-dose group: 0.25 g (5 g / kg) of crude drug per ml;

[0139] (4) Medium-dose group: 0.5 g (10 g / kg) of crude drug per ml;

[0140] (5) High-dose group: 1 g (20 g / kg) of crude drug per ml;

[0141] 1. Anti-gastric ulcer effect: effect on water immersion stress ulcer in rats

[0142] Method: Take rats weighing 150-180 g, male and female, fast (without water) for 24 hours, and then randomly divide them into 5 groups. The administration groups are given high, medium and low doses of the traditional Chinese medicine composition of Example 1 of the present application by gavage, the control group is given equal volume of normal saline by gavage, and the positive drug group is given cimetidine by gavage. 30 minutes after administration, ether is used to lightly anesthetize the rats, which are then fixed in an upright position on a test tube holder, and then the fixed rats are vertically immersed in a constant temperature water tank at 23℃, with the water surface reaching the xiphoid process. 18 hours later, the rats are sacrificed, the abdomen is opened, the pylorus and cardia are ligated, and then 5 ml of 1% formalin is injected from the glandular stomach, the stomach is placed in 1% formalin solution for 10 minutes, the stomach is cut along the greater curvature, the contents are washed out, and the ulcer lesions are examined. The millimeter sum of the ulcer length is taken as the ulcer index, statistical processing is performed, the ulcer inhibition percentage is calculated, and the effect of the drug is evaluated.

[0143]

[0144] Results: The medicinal composition of Example 1 of the present application can significantly inhibit water immersion stress-induced gastric ulcer, and has a significant difference compared with the control group, and the results are shown in Table 8 below.

[0145] Table 8 Effects on water immersion stress-induced gastric ulcer in rats

[0146]

[0147] Compared with the negative control group: **: P < 0.01, ***: P < 0.001.

[0148] 2. Anti-gastric ulcer effect: effect on acetic acid damage-induced gastric ulcer

[0149] Method: Take rats weighing 150-180 g, male and female, fast for 12 hours, and randomly divide into 5 groups: negative control group, positive control group (cimetidine), high, medium and low dose groups of the medicinal composition of Example 1 of the present application. In a semi-fasting state, the animals are anesthetized with ether, then fixed in a supine position on the operating table. The abdominal wall hair is cut, and the abdomen is routinely disinfected. A 2-2.5 cm incision is made in the middle of the abdomen under the xiphoid process, and the glandular stomach is gently pulled out of the abdomen. 100% glacial acetic acid 0.05 ml is dropped into the specially designed glass tube to contact the serosal surface for 1 minute, and the cotton ball is wiped off. The stomach is gently returned, and the skin is sutured in layers. The rats are routinely fed. From the next day of the operation, the rats are randomly divided into groups. The rats in the drug groups are given high, medium and low doses of the medicinal composition of Example 1 by gavage, and the rats in the control groups are given the same volume of normal saline by gavage, and the rats in the positive drug group are given cimetidine by gavage. Continuous treatment for 11 days, on the 12th day, the rats are sacrificed, the pylorus and cardia are ligated, and the stomach is immersed in 1% formalin solution for 10 minutes. The stomach is cut along the greater curvature, the contents are washed, and the ulcer is examined. The mean of the longest diameter and the shortest diameter of the ulcer is used to represent the ulcer index, and statistical processing is performed to calculate the ulcer healing percentage and evaluate the promoting effect of the drug on ulcer healing.

[0150] Results: The medicinal composition of the present application can significantly inhibit acetic acid damage-induced gastric ulcer, and has a significant difference compared with the control group, and the results are shown in Table 9.

[0151] Table 9 Effects on acetic acid damage-induced gastric ulcer in rats

[0152]

[0153] Compared with the negative control group: **: P < 0.01, ***: P < 0.001.

[0154] Effect Example E3 Effect of the medicinal composition of the present application on gastric emptying in mice

[0155] Dose: (1) Negative control group: equal volume of normal saline

[0156] (2) Positive control group: 0.06 mg of domperidone (1.2 mg / kg) per ml;

[0157] (3) Low dose group: 0.16 g of crude drug (3.2 g / kg) per ml;

[0158] (4) Medium dose group: 0.32 g of crude drug (6.4 g / kg) per ml;

[0159] (5) High dose group: 0.64 g of crude drug (12.8 g / kg) per ml;

[0160] Method: 20-22 g mice were taken, both male and female were used, 12 hours of fasting before the experiment, free water, randomly divided into 5 groups: negative control group, positive control group (domperidone), high, medium and low dose groups of the traditional Chinese medicine composition in Example 1. In order to avoid the color interference of traditional Chinese medicine itself, subcutaneous administration was adopted, 0.2 ml of 0.1% methyl orange solution was given by gavage 30 minutes later, and the mice were sacrificed by dislocation 20 minutes later, the stomach was taken by laparotomy, placed in a small beaker, 10 ml of distilled water was added, the stomach was cut along the greater curvature, and the stomach contents were washed in distilled water, 5% sodium bicarbonate solution was used to adjust pH to 6.0-6.5, and centrifugation was carried out at 2000 rpm for 10 minutes, the supernatant was colorimetric at 420 nm, distilled water was used as zero, and 0.1% methyl orange 0.2 ml was added to 10 ml of distilled water as the base methyl orange optical density.

[0161]

[0162] Results: The subcutaneous injection of the traditional Chinese medicine composition in the application for 3 days can reduce the methyl orange residual rate in the stomach, and there is a significant difference compared with the control group; the results are shown in Table 10.

[0163] Table 10 Influence on gastric emptying of mice (X ± SD)

[0164]

[0165] Compared with the negative control group: **: P < 0.01, ***: P < 0.001

[0166] Effect Example E4 Influence of the traditional Chinese medicine composition in the application on the small intestine propulsion of mice

[0167] Dose: (1) Negative control group: equal volume of normal saline;

[0168] (2) Positive control group: 0.06 mg of domperidone (1.2 mg / kg) per ml;

[0169] (3) Low dose group: 0.16 g of crude drug (3.2 g / kg) per ml;

[0170] (4) Medium dose group: 0.32g (6.4g / kg) of crude drug per ml;

[0171] (5) High dose group: 0.64g (12.8g / kg) of crude drug per ml;

[0172] Method: Take adult mice that have fasted for 24 hours, half male and half female, and randomly divide them into 5 groups: negative control group, positive control group (domperidone), high, medium and low dose groups of the traditional Chinese medicine composition in Example 1. Gavage with a drug solution containing 50% ink, and 20 minutes after administration, cervical dislocation, open the abdominal cavity, isolate the mesentery, cut the intestinal canal from the upper end to the pylorus and from the lower end to the ileocecal junction, place it on glass paper, gently stretch the small intestine into a straight line, measure the length of the intestinal canal as the total length of the small intestine, and the distance from the pylorus to the ink front as the "ink propulsion distance in the intestine".

[0173]

[0174] Results: The traditional Chinese medicine composition in Example 1 significantly increases small intestinal propulsion movement, and has a significant difference compared with the control group, but has no obvious effect on small intestinal volume, and the results are shown in Table 11.

[0175] Table 11 Influence on small intestinal propulsion movement of mice (X ± SD)

[0176]

[0177] Compared with the negative control group: *P<0.05, **P<0.01.

[0178] Effect Example E5 Influence of the traditional Chinese medicine composition on the composition of rat gastric juice

[0179] Dose: (1) Negative control group: equal volume of normal saline

[0180] (2) Positive control group: 24mg (0.48g / kg) of white capsule per ml

[0181] (3) Low dose group: 0.16g (3.2g / kg) of crude drug per ml

[0182] (4) Medium dose group: 0.32g (6.4g / kg) of crude drug per ml

[0183] (5) High dose group: 0.64g (12.8g / kg) of crude drug per ml

[0184] Method: Take 180-200g rats, fasting for 24 hours, free water, randomly divided into 5 groups: negative control group, positive control group (Jiebai capsule), the high, medium and low dose groups of the traditional Chinese medicine composition in Example 1. Ether light anesthesia, cut off the abdominal hair, conventional disinfection, open a 2.5cm incision along the abdominal white line under the xiphoid, carefully lift the stomach, and ligate the junction of the pylorus and duodenum with a suture, immediately inject the test drug into the duodenum. After suture, send back to the cage, fasting and water deprivation after operation, 3 hours later, cervical dislocation, remove the stomach, collect the gastric juice in a calibrated centrifuge tube, centrifuge at 3000rpm for 15 minutes, and collect the supernatant to calculate the gastric juice volume and perform gastric juice analysis.

[0185] 1. Gastric acid determination: the supernatant is determined by pH value with acidity meter as free acid content. Take 1.0ml of gastric juice into a small beaker, add one drop of phenolphthalein indicator, and titrate with 0.01mol / L sodium hydroxide until pink color appears as the end point.

[0186] Total acidity (mmol / L) = sodium hydroxide milliliters x 10

[0187] Total acid output (umol / L) = total acidity x gastric juice volume per hour

[0188] 2. Pepsin activity determination: after the egg white is fully beaten, it is filtered with gauze, and the inner diameter 1mm capillary tube is filled with egg white, then placed in 85℃ hot water to make the protein coagulate, and stored in the refrigerator for standby. Take 1ml of gastric juice into a triangular flask, add 15ml of 0.05mol / L hydrochloric acid solution, shake well, put in two protein tubes, seal the bottle opening, and incubate in a 37℃ constant temperature water bath for 24h, take out the protein tube, measure the length (mm) of the transparent part at both ends of the protein tube, and take the average value of the four ends.

[0189] Pepsin activity unit = average value 2 x 16

[0190] Results: The traditional Chinese medicine composition has no obvious effect on gastric juice secretion, acidity and pepsin activity, and the results are shown in Table 12.

[0191] Table 12 Determination results of rat gastric juice pepsin activity (X±SD)

[0192]

[0193] Compared with the negative control group: *: P<0.05.

[0194] Effect Example E6 Anti-inflammatory and analgesic effect of the traditional Chinese medicine composition

[0195] 1. Anti-inflammatory effect

[0196] Dose: (1) Negative control group: equal volume of normal saline

[0197] (2) Positive control group: 1.2 mg of ibuprofen (24 mg / kg) per ml

[0198] (3) Low dose group: 0.25 g of crude drug (5 g / kg) per ml

[0199] (4) Medium dose group: 0.5 g of crude drug (10 g / kg) per ml

[0200] (5) High dose group: 1.0 g of crude drug (20 g / kg) per ml

[0201] Method: Male rats weighing 120-150 g were randomly divided into 5 groups, namely, negative control group, positive control group, and high, medium, and low dose groups of the traditional Chinese medicine composition in Example 1. Then, the rats were anesthetized by intraperitoneal injection of sodium pentobarbital 30 mg / kg, the left and right sides of each rat were disinfected with iodine, and after the iodine was removed with a 75% alcohol cotton ball, a 1 cm long incision was made, 40 mg of a high-pressure sterilized cotton ball (soaked in a penicillin and streptomycin mixture 0.2 ml and dried) was implanted subcutaneously from the incision with a forceps, and then the skin was sutured. From the day of the operation, the rats were orally administered with normal saline and the traditional Chinese medicine composition in Example 1, and the administration was continuously performed for 6 days. On the 7th day, the incision was opened, the cotton ball was taken out together with the surrounding connective tissue, the cotton ball and adipose tissue were removed, and then the sample was dried in an oven at 70°C and weighed.

[0202] Result: The traditional Chinese medicine composition has a significant inhibitory effect on the cotton ball granuloma of the rats, and there is a significant difference compared with the control group, which indicates that the traditional Chinese medicine composition has a significant anti-inflammatory effect, and the results are shown in Table 13.

[0203] Table 13 Influence on the formation of cotton ball granuloma in rats (X ± SD)

[0204]

[0205] Compared with the negative control group: *P <0.05, ***P <0.001.

[0206] 2. Analgesic effect

[0207] Dose: (1) Negative control group: equal volume of normal saline

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

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

[0210] (4) Medium dose group: 0.5 g of crude drug (10 g / kg) per ml

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

[0212] Select 18-22 g mice, 0.5 h after administration, ip 0.6% acetic acid 0.1 ml / 10 g per mouse, record the time of mouse writhing after injection of acetic acid and the number of writhing of each mouse within 10 min and 30 min, compare the differences between groups, and calculate the analgesia percentage.

[0213] Results: The first writhing time of mice after oral administration of the traditional Chinese medicine composition of the present application was prolonged, and there was a very significant difference (P<0.01) compared with the normal saline group. The number of writhing within 10 min and 30 min was decreased, and the difference was significant compared with the normal saline group, indicating that the traditional Chinese medicine composition of Example 1 of the present application has a clear analgesic effect. The results are shown in Table 14.

[0214] Table 14 Analgesic effect

[0215]

[0216] Compared with the negative control group**:P<0.01.

[0217] The above experimental results show that the traditional Chinese medicine composition of the present application can significantly reduce the occurrence of water immersion stress and acetic acid burn damage type gastric ulcer in rats, significantly reduce the residual rate of methyl orange in the stomach of mice, has no obvious effect on gastric juice secretion, acidity and gastric enzyme activity, promotes small intestine emptying, reduces the weight of cotton ball granuloma in rats, thereby proving that the traditional Chinese medicine composition of the present application has the effects of inhibiting ulcer, reducing the residual rate of methyl orange in the stomach of mice, having no obvious effect on gastric juice secretion, acidity and gastric enzyme activity, promoting small intestine emptying, reducing the weight of cotton ball granuloma in rats, and obvious analgesic effect.

[0218] The above is only the preferred specific embodiment of the present application, but the protection scope of the present application is not limited thereto, any change or replacement easily thought of by those skilled in the art within the technical range disclosed by the present application should be covered in the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. A traditional Chinese medicine composition for treating functional dyspepsia complicated with anxiety and depression, characterized in that, It is made from the following Chinese medicinal 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, Citrus aurantium 150-521 parts.

2. The traditional Chinese medicine composition 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, 50-400 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 composition 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 composition 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 composition according to claim 1, characterized in that, Made from the following parts by weight of traditional Chinese medicine raw materials: 446 portions of Pinellia ternata, 209 portions of Coptis chinensis, 298 portions of Scutellaria baicalensis, 357 portions of dried ginger, 179 portions of ginseng, 238 portions of licorice, 357 portions of jujube, and 298 portions of Citrus aurantium.

6. The traditional Chinese medicine composition according to any one of claims 1-5, characterized in that, The composition is a pharmaceutical preparation.

7. The traditional Chinese medicine composition according to claim 6, characterized in that, The pharmaceutical preparation also includes pharmaceutical excipients.

8. The traditional Chinese medicine composition according to claim 6, characterized in that, The pharmaceutical preparation includes at least one of the following forms: tablets, capsules, lozenges, granules, pills, powders, elixirs, suspensions, solutions, injections, suppositories, sprays, drops, drop pills, and patches.

9. A method for preparing the traditional Chinese medicine composition according to any one of claims 1-5, characterized in that... include: The formula uses eight Chinese medicinal herbs: Pinellia ternata, Coptis chinensis, Scutellaria baicalensis, dried ginger, ginseng, licorice, jujube, and Citrus aurantium. Preparation steps of Coptis chinensis: Coptis chinensis is extracted by reflux with ethanol, and the extract is concentrated under reduced pressure to obtain Coptis chinensis concentrate; Ginseng preparation steps: Ginseng is added to ethanol for reflux extraction, and the extract is concentrated under reduced pressure to obtain ginseng concentrate; Water extraction steps: Add water to the remaining six ingredients and decoct. Centrifuge and concentrate the extract to obtain a concentrated water extract. The Coptis chinensis concentrate, ginseng concentrate, and water extract concentrate are combined to prepare the traditional Chinese medicine composition.

10. The preparation method according to claim 9, characterized in that: The water extraction step can also be performed using the following steps: The remaining six ingredients 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 aqueous extract.

11. The preparation method according to claim 9 or 10, characterized in that: In the preparation steps of Coptis chinensis, 1-20 times the amount of ethanol is added, the ethanol concentration is 1-80%, and the mixture is heated and refluxed for extraction 1-3 times, each time for 0.5-6 hours, and concentrated to a relative density of 1.05-1.

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

18. 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.

18.

12. The preparation method according to claim 9, characterized in that: In the preparation steps of Coptis chinensis, Coptis chinensis is added with 8 times the amount of 70% ethanol, heated and refluxed for 3 times, 1 hour each time, filtered, and the extract is concentrated under reduced pressure to a relative density of 1.05-1.

18. In the ginseng preparation steps, 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.

18. 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 then centrifuged and concentrated to a relative density of 1.05-1.

18. A traditional Chinese medicine composition was prepared by combining concentrated extracts of Coptis chinensis, ginseng, and water.

13. The preparation method according to claim 10, characterized in that: In the preparation steps of Coptis chinensis, Coptis chinensis is added with 8 times the amount of 70% ethanol, heated and refluxed for 3 times, 1 hour each time, filtered, and the extract is concentrated under reduced pressure to a relative density of 1.05-1.

18. In the ginseng preparation steps, 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.

18. 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.

18. A traditional Chinese medicine composition was prepared by combining concentrated extracts of Coptis chinensis, ginseng, and water.

14. The preparation method according to claim 9 or 10, characterized in that, The traditional Chinese medicine composition 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.

18. (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.

18. (3) Combine the concentrated extracts of Coptis chinensis and ginseng, and spray dry them to obtain Coptis chinensis and ginseng spray-dried powder; (4) Add 1-20 times the amount of water to the dregs of Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, Citrus aurantium and / or ginseng and Coptis chinensis after alcohol extraction, 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 1.05-1.18, spray dry the concentrate to obtain the six-ingredient spray-dried powder; (5) Mix the spray-dried powders of Coptis chinensis, ginseng, and Pinellia ternata, and granulate them to obtain granules.

15. The preparation method according to claim 14, characterized in that: In step (5), the spray-dried powders of Coptis chinensis and ginseng, the spray-dried powders of Pinellia ternata and other six herbs are mixed with an appropriate amount of dextrin and sucralose, and then granulated to obtain granules.

16. The preparation method according to claim 14, 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 to 1.

18. In step (2), ginseng is added to 8 times the amount of 50% ethanol, heated and refluxed three times for 1 hour each time, filtered, and the ethanol in the filtrate is recovered under reduced pressure and concentrated to a relative density of 1.05 to 1.

18. In step (4), Pinellia ternata, dried ginger, Scutellaria baicalensis, jujube, licorice, and Citrus aurantium are decocted three times with 8 times the amount of water for 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.

18. The concentrate is then spray-dried. In step (5), the spray-dried powders of Coptis chinensis and ginseng, the spray-dried powders of Pinellia ternata and other six herbs are mixed with an appropriate amount of dextrin and sucralose, and then granulated to obtain granules.

17. The use of the traditional Chinese medicine composition according to any one of claims 1-8 in the preparation of drugs for functional dyspepsia, depression, anxiety, functional dyspepsia combined with anxiety and depression, gastrointestinal motility, gastric emptying, gastroparesis, gastric ulcer, anti-inflammatory and / or analgesic.

Images