A Chinese medicine composition for treating functional dyspepsia and its preparation method and use

Abstract

The present invention relates to a Chinese medicine composition for treating functional dyspepsia, which is prepared from the following Chinese medicine raw materials: pinellia, scutellaria, coptis, dried ginger, codonopsis, amomum, rhubarb, curcuma, magnolia bark, white peony root, corydalis, liquorice, jujube. The preparation method is to decoct in water for multiple times, filter, collect the filtrate, and prepare the corresponding preparation. The preferred preparation is a granule. The Chinese medicine composition has excellent clinical effects in treating functional dyspepsia, especially for patients showing symptoms of cold and heat, liver and stomach disharmony, spleen deficiency and qi stagnation, epigastric fullness or distending pain, poor appetite, dry throat, intestinal rumbling and loose stools, pale tongue with yellow or greasy fur, and stringy and thin pulse, and can also improve mental symptoms such as anxiety and depression related to functional dyspepsia.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine for treating functional dyspepsia. Background Art

[0002] Functional dyspepsia (FD) mainly refers to a group of clinical syndromes in which patients suffer from upper abdominal pain, burning sensation, postprandial fullness, and early satiety, which may be accompanied by indigestion symptoms such as loss of appetite, belching, nausea and vomiting, excluding organic diseases that cause the above symptoms. The onset of symptoms lasts for more than 3 months and the course of the disease is more than 6 months. Studies have found that the prevalence of FD is related to gender, age, race, living environment, family cultural background, and economic situation. Genetic susceptibility, food and drugs, personality traits, and Helicobacter pylori, which is currently receiving more attention, also have a certain impact on it. The global prevalence of dyspepsia is 7% to 45%; the prevalence of FD in Asia is 8% to 23%, and with the accelerated pace of life and the increase in mental stress, the incidence of FD has a tendency to gradually increase.

[0003] The causes of functional dyspepsia mainly include psychological factors, food and abnormal eating behavior, Helicobacter pylori infection (Hp), genetic factors, etc. Its pathogenesis involves multiple mechanisms such as gastric capacity restriction disorder, gastric motility disorder, visceral hypersensitivity, and neuro-endocrine regulation disorder.

[0004] Patients with functional dyspepsia have an inflammatory reaction in the local gastrointestinal mucosa, patients with Hp infection have increased gastric acid secretion, patients with FD have delayed gastric emptying, limited postprandial relaxation of the gastric fundus, and increased sensitivity to gastric distension. Psychological stress, especially anxiety, is significantly associated with FD, and gastrointestinal symptoms appear before anxiety, suggesting that there may be gastrointestinal-driven brain dysfunction. 40% of FD patients have duodenitis, especially duodenal eosinophilia, and some patients may have excessive eosinophil clusters and eosinophil degranulation near nerves. A high-fat diet can affect the pathophysiology of the gastroduodenum by changing the response of gastrointestinal hormones, such as increased levels of multiple hormones including cholecystokinin.

[0005] FD has no characteristic clinical manifestations, mainly including upper abdominal pain, upper abdominal distension, early satiety, heat, loss of appetite, nausea, vomiting, etc. Symptoms may appear alone or in a group. Early satiety refers to a feeling of fullness soon after eating, resulting in a significant reduction in food intake. Upper abdominal distension often occurs after a meal, or worsens after a meal. Early satiety and upper abdominal distension are often accompanied by heat. Nausea and vomiting are not common, and often occur in patients with significantly delayed gastric emptying, and vomiting is mostly the stomach contents of the meal. Many patients also have mental symptoms such as insomnia, anxiety, depression, headache, and inattention. These symptoms are related to the "cancer fear" mentality in some patients. Symptoms may also change during the course of the disease, with a slow onset, persistence or recurrence over the years, and many patients have dietary, mental and other inducing factors.

[0006] Functional dyspepsia should be differentiated from secondary dyspepsia: Secondary dyspepsia refers to patients with clear organic or metabolic diseases caused by dyspepsia symptoms, which can be confirmed by traditional diagnostic methods. The symptoms of secondary dyspepsia will improve as the primary disease improves or is controlled (such as after the elimination of Hp infection, the healing of ulcers, etc.).

[0007] There is still no specific gold standard for the treatment of FD. Although FD is not life-threatening, it plagues patients for a long time, seriously affects people's quality of life, wastes medical resources, and brings heavy economic and mental burdens to society and families. Therefore, continued efforts are needed for the treatment of FD. Currently, the commonly used treatment methods are: 1) Change lifestyle, general methods such as eating small meals, avoiding coffee, ethanol, non-steroidal anti-inflammatory drugs, greasy or spicy foods, and eating regularly. Although there is not enough evidence to prove that these have a therapeutic effect on FD, they have an auxiliary effect on the treatment of FD. In addition, music ultrasound therapy can be performed at ordinary times to improve the physical and mental environment and facilitate recovery. 2) Anti-Hp treatment, Hp infection is related to the symptoms of FD to a certain extent, and some patients can obtain symptom relief through anti-Hp treatment. 3) Gastrointestinal prokinetic drugs are commonly used in clinical practice for upper abdominal discomfort, such as mosapride and itopride. 4) Acid suppressants. Commonly used drugs include H2 receptor antagonists and proton pump inhibitors. They reduce gastric acid secretion and reduce gastrointestinal sensitivity by inhibiting gastric acid secretion, which has a certain effect on alleviating upper abdominal pain and burning sensation in FD patients. 5) Psychological therapy. Psychological therapy can be used as a remedial treatment for FD patients with severe symptoms and ineffective drug treatment. 6) Traditional Chinese medicine, syndrome differentiation and treatment, and acupuncture are effective in treating FD.

[0008] According to relevant clinical reports, Western medicine has good short-term effects in treating functional dyspepsia, but poor long-term effects. Therefore, the use of traditional Chinese medicine to treat functional dyspepsia has a good application prospect, and clinical verification shows that traditional Chinese medicine is effective in treating functional dyspepsia. However, traditional Chinese medicine usually needs to be differentiated according to the specific symptoms of the patient, so as to use specialized medicine. There is a lack of traditional Chinese medicine prescriptions that can be widely used in various patients to treat functional dyspepsia.

[0009] Functional dyspepsia belongs to the category of "fullness" and "epigastric pain" in traditional Chinese medicine. Its basic pathogenesis is the blockage of the middle-jiao qi and the abnormal ascending and descending of qi. Traditional Chinese medicine believes that the main causes of functional dyspepsia are invasion of exogenous pathogens, weak spleen and stomach, emotional distress, and eating disorders.

[0010] The inventor of this application has conducted long-term and extensive research on the treatment of functional dyspepsia based on Banxia Xiexin Decoction for many years, and proposed that the treatment method can be adopted by using pungent and bitter, tonifying and purging, etc. Banxia Xiexin Decoction is considered to be a representative prescription for treating gastrointestinal diseases and pungent and bitter. Banxia Xiexin Decoction originated from Treatise on Febrile and Miscellaneous Diseases, and it uses both cold and hot, tonifying and purging, and is cleverly matched. Banxia Xiexin Decoction appears once in "Treatise on Febrile Diseases" and "Golden Chamber". Article 149 of "Treatise on Febrile Diseases" reads: "If a patient has fever for five or six days and has all the symptoms of Bupleurum, but other medicines are used to treat it...but the patient feels full but not painful, it is called abdominal distension, and Bupleurum is not suitable for it. Banxia Xiexin Decoction is suitable." "Golden Chamber" states: "If the patient has vomiting, intestinal rumbling, and abdominal distension, Banxia Xiexin Decoction is the main treatment." Scutellaria baicalensis and Coptis chinensis descend the stomach qi upward; dried ginger and Pinellia ternata are pungent drugs that can disperse the spleen's cold. Combined with the sweet and warm drugs, white ginseng and licorice, they nourish the middle and replenish qi, harmonize the spleen and stomach, and replenish the middle qi. The ancients summarized it as "the method of pungent to open, bitter to descend, and sweet to regulate". Although it is a painful disease, the dialectical approach is proper and the therapeutic effect is remarkable.

[0011] In 2013, the inventor team published the article "Clinical Observation on 60 Cases of Functional Dyspepsia Treated with Banxia Xiexin Decoction" (Li Xin, Chinese Journal of Traditional Chinese Medicine, April 2013), in which the treatment group was treated with Banxia Xiexin Decoction, with specific prescriptions: 10g each of Pinellia, Dry Ginger, and Scutellaria, 8g of Coptis, 12g of Codonopsis, 6g of Roasted Licorice, and 12g of Jujube. Additions and subtractions: For abdominal distension and belching, add Citrus aurantium and Magnolia officinalis; for depression, add Curcuma and Albizzia; for constipation, add Rhubarb, Cannabis Seed, and Prunus mume; for abdominal pain, add stir-fried White Peony Root and Vinegar Corydalis; for thick and greasy tongue coating, add Amomum villosum and Atractylodes macrocephala. Decoction in water, 1 dose per day, decocted twice, a total of 300mL of juice, taken twice before breakfast and before bedtime.

[0012] On the basis of the above clinical practice disclosed by the inventor team, other researchers in this field have carried out a lot of imitation and clinical use. For example, prior art 1 "Observation on the efficacy of Banxia Xiexin Decoction in the treatment of functional dyspepsia" (Deng Xiajie, Clinical Medical Research and Practice, 2016) discloses the use of Banxia Xiexin Decoction for the treatment of functional dyspepsia. The selected patients all meet the Rome II functional dyspepsia diagnostic criteria; no gastric motility and antidepressant drugs have been used in the past two weeks. Basic prescription: 12g of Scutellaria baicalensis, 9g of Pinellia ternata, 12g of Codonopsis pilosula, 4 pieces of jujube, 10g of dried ginger, 5g of roasted licorice, and 12g of Coptis chinensis. And the drugs can be increased according to the main symptoms of the patient: patients with constipation can add 9g of rhubarb, 12g of Prunus mume, and 12g of hemp seed; patients with abdominal pain can add 12g of vinegar-corydalis and 12g of stir-fried white peony root; patients with abdominal distension can add 12g of immature bitter orange and 12g of Magnolia officinalis; patients with emotional depression can add 12g of Albizzia julibrissin and 15g of Curcuma; patients with thick and greasy tongue coating can add 15g of Atractylodes macrocephala and 12g of Amomum villosum. The above drugs are decocted in water, 1 dose / d, taken in the morning and evening.

[0013] Prior art 2 "Study on the efficacy of modified Banxia Xiexin Decoction in the treatment of functional dyspepsia" (Wang Dong, Capital Food and Medicine, 2017) discloses a method for treating functional dyspepsia, namely, modified Banxia Xiexin Decoction for treatment. The formula of Banxia Xiexin Decoction: 12.0g Codonopsis pilosula, 12.0g jujube, 10.0g dried ginger, 10.0g Pinellia, 10.0g Scutellaria, and 6.0g roasted Licorice. Add or subtract: If the patient has abdominal distension and belching during the treatment, increase 10.0g of Citrus aurantium and 10.0g of Magnolia officinalis. For patients with depression, add 10.0g of Curcuma aromatica and 10.0g of Albizzia julibrissin. For patients with constipation, add 10.0g of Rhubarb, 10.0g of Cannabis sativa seed, and 10.0g of Prunus mume. If the patient has abdominal pain, add 15.0g of stir-fried White Peony Root and 10.0g of Vinegar-corylifolia. For patients with thick and greasy tongue coating, add 10.0g of Amomum villosum and 10.0g of Atractylodes macrocephala. Decoction with water, take one dose twice a day, decoct 300ml, take before breakfast and before bedtime, and treat for a total of four weeks.

[0014] Prior art 3 "Clinical efficacy of Banxia Xiexin Decoction for the treatment of functional dyspepsia" (Tian Lingzhen, Great Doctor, 2018) Banxia Xiexin Decoction is used to treat functional dyspepsia, and the prescription is: 10g each of Pinellia, dried ginger and Scutellaria; 8g Coptis and 12g Codonopsis; 6g roasted licorice and 12g jujube. Additions and subtractions: For patients with abdominal distension and belching, add Zhishi and Magnolia officinalis; for patients with more depressed mood, add Curcuma and Albizzia; for patients with constipation, add Rhubarb, Cannabis and Prunus mume; for patients with abdominal pain, add stir-fried white peony and vinegar Corydalis; for patients with thick and greasy tongue coating, add Amomum and Atractylodes, etc. Decoction in water, 1 dose / d, decoct twice, take twice, 150mL / time, warm before breakfast and before bedtime.

[0015] Although the above-mentioned prior art notes the use of Banxia Xiexin Decoction to treat functional dyspepsia, it can be seen from the content of the above-mentioned prior art that they have not yet formed a fixed prescription for treating functional dyspepsia, but are only a clinical treatment plan that requires symptom identification and application. For example, when encountering patients with thick and greasy tongue coating, it is necessary to add Atractylodes macrocephala and Amomum villosum, but if there is no symptom of thick and greasy tongue coating, there is no need to use Atractylodes macrocephala and Amomum villosum. In other words, these prior arts all need to choose to use different drugs according to the specific patients, and have not formed a fixed prescription suitable for various types of functional dyspepsia. Moreover, in the process of clinical verification, the inventor found that the raw material compatibility and dosage ratio of the above-mentioned prescription were not reasonable, and the effect of Banxia Xiexin Decoction could not be fully exerted, and the effect of treating functional dyspepsia was not satisfactory.

[0016] In fact, the inventor of this application has carried out long-term and extensive research on the treatment of related diseases based on Banxia Xiexin Decoction for 35 years. In 1994, the inventor published the article "Clinical Study on the Treatment of Non-ulcer Dyspepsia with Weikangning" (Chinese Medicine Research, Issue 2, 1994), which disclosed that Weikangning Capsules are decocted, extracted, filtered, concentrated into paste and dried by scutellaria, dried ginger, coptis, white peony root, rhubarb, etc., and dried and powdered by ginger pinellia, coptis, and amomum villosum, and passed through an 80-mesh sieve, mixed and filled into capsules, 0.5 grams per capsule. The use of Weikangning Capsules for non-ulcer dyspepsia has achieved good therapeutic effects. Subsequently, the inventor and the inventor's team conducted long-term research and improvement on the formulation raw materials and dosage ratio of Weikangning.

[0017] The inventor team published "The effect of pungent opening and bitter descending method on gastric contraction and relaxation activity in rats with functional dyspepsia" (Wang Yi, Journal of Traditional Chinese Medicine, May 2010) and "Experimental study on the effect of pungent opening and bitter descending method on plasma NO, gastric body NOS ICC and SMC in FD rats" (Wang Yi, Liaoning Journal of Traditional Chinese Medicine, 2009) also disclosed that Weikangning Capsules are decocted, extracted, filtered, concentrated into paste, dried, ginger pinellia, coptis root, and amomum villosum in equal amounts, dried and powdered, passed through an 80-mesh sieve, mixed and packed into capsules, 0.5g / capsule. This technical solution further adds bupleurum, licorice and jujube on the basis of the 1994 solution.

[0018] The inventor team published "Effect and safety evaluation of the method of pungent opening and bitter descending in the treatment of functional dyspepsia" (Wang Bei, China Medical Guide, September 2016) and "Observation on the psychological efficacy of Weikangning in the treatment of patients with functional dyspepsia with mixed cold and heat syndrome" (Yang Guigui, Chinese Journal of Integrated Traditional and Western Medicine, May 2017), which also disclosed the representative prescription of the method of pungent opening and bitter descending, Weikangning, with the specific drug composition of: 9g of ginger pinellia, 5g of coptis root, 6g of amomum, 9g of scutellaria, 9g of dried ginger, 15g of codonopsis, 9g of curcuma, 9g of magnolia bark, 15g of white peony root, 10g of vinegar corydalis, 9g of bupleurum, 6g of rhubarb, 9g of stir-fried almonds, 9g of roasted licorice, and 4 jujubes. This technical solution further adds bupleurum, stir-fried almonds, roasted licorice and jujube.

[0019] Patent CN201810938207.1 applied by the inventor team discloses a Chinese medicine composition for treating indigestion, which is made of the following raw materials: 4-25 parts by weight of Pinellia, 2-20 parts by weight of Coptis, 3-22 parts by weight of Scutellaria, 3-22 parts by weight of Dry Ginger, 8-30 parts by weight of Codonopsis, 4-25 parts by weight of Magnolia, 3-22 parts by weight of Bupleurum, 9-35 parts by weight of Curcuma, 8-30 parts by weight of White Peony, 4-25 parts by weight of Corydalis, 3-22 parts by weight of Licorice, and 1-7 parts by weight of Jujube. This technical solution adds Bupleurum and simplifies Amomum and Rhubarb.

[0020] The paper “Exploring “Brain-Gut Synchrony” to Treat Common Functional Gastrointestinal Disorders” (Mao Xinyong, Chinese Journal of Integrated Traditional and Western Medicine, May 2020) published by the inventor team disclosed the representative prescription of the acrid-opening and bitter-downward-regulating pivot method, Weikangning (Ginger Pinellia, Coptis chinensis, Amomum villosum, Scutellaria baicalensis, Dry Ginger, Codonopsis pilosula, Curcuma aromatica, Magnolia officinalis, White Peony Root, Vinegar-corylifolia, Bupleurum chinense, Rhubarb, Stir-fried Apricot Kernel, and Roasted Licorice). This technical solution once again added Amomum villosum and Rhubarb, while simplifying the jujube.

[0021] The inventor team published "Application of Brain-Intestine Coordination Therapy in Digestive Psychosomatic Diseases" (Zhang Tao, Chinese Journal of Integrated Traditional and Western Medicine, 2022, https: / / kns.cnki.net / kcms / detail / 11.2787.R.20221111.1331.002.html) which disclosed that the drug composition of Weikangning Recipe includes: Pinellia ternata, Coptis chinensis, Amomum villosum, Scutellaria baicalensis, Dry ginger, Codonopsis pilosula, Curcuma aromatica, Magnolia officinalis, White Peony Root, Vinegar Corydalis, Bupleurum, Rhubarb, Roasted Licorice, and Jujube. This scheme adds jujube again, while streamlining bitter almonds.

[0022] It can be seen that technical personnel including the team of inventors of this application have conducted extensive and in-depth research on the use of Banxia Xiexin Decoction to treat functional dyspepsia, and have been looking for a technical solution with optimal raw material composition and weight compatibility in the treatment of functional dyspepsia. It is based on such technical pursuits that the inventors completed the technical solution of this application. Summary of the invention

[0023] In order to solve the problem in the prior art that the composition and dosage compatibility of raw materials are still imperfect when using Banxia Xiexin Decoction to treat functional dyspepsia, based on the many years of research by the inventors of this application as described in the background technology, the purpose of the present invention is to provide a Chinese medicine composition for treating functional dyspepsia, which has the advantages of simplified formula, reasonable selection of raw materials, comprehensive efficacy, etc., and the effect of treating functional dyspepsia is greatly improved.

[0024] In order to achieve the above object, the technical solution of the present invention is as follows:

[0025] A Chinese medicine composition for treating functional dyspepsia is prepared from the following Chinese medicine raw materials in parts by weight:

[0026] 6-11 parts of ginger pinellia, 6-11 parts of wine scutellaria, 3-7 parts of wine coptis, 6-11 parts of dried ginger, 6-11 parts of codonopsis pilosula, 3-8 parts of amomum, 2-6 parts of raw rhubarb, 3-11 parts of curcuma, 7-11 parts of magnolia bark, 6-11 parts of stir-fried white peony root, 8-12 parts of vinegar corydalis, 4-9 parts of roasted licorice, and 4-9 parts of jujube.

[0027] Preferably, the Chinese medicine composition for treating functional dyspepsia is prepared from the following Chinese medicine raw materials in parts by weight:

[0028] 7-11 parts of ginger pinellia, 7-11 parts of wine scutellaria, 3-7 parts of wine coptis, 7-11 parts of dried ginger, 7-11 parts of codonopsis pilosula, 4-8 parts of amomum, 2-4 parts of raw rhubarb, 7-11 parts of turmeric, 7-11 parts of magnolia bark, 7-11 parts of stir-fried white peony root, 8-12 parts of vinegar corydalis, 4-8 parts of roasted licorice, and 4-8 parts of jujube.

[0029] More preferably, the Chinese medicine composition for treating functional dyspepsia is prepared from the following Chinese medicine raw materials in parts by weight:

[0030] 9 parts of ginger pinellia, 9 parts of wine scutellaria, 5 parts of wine coptis, 9 parts of dried ginger, 9 parts of codonopsis, 6 parts of amomum, 3 parts of raw rhubarb, 9 parts of curcuma, 9 parts of magnolia bark, 9 parts of stir-fried white peony root, 10 parts of vinegar corydalis, 6 parts of roasted liquorice, and 6 parts of jujube.

[0031] Further preferably, the Chinese medicine raw materials of the present invention are conventional raw materials in the art, and their corresponding plant sources and medicinal parts are known and commonly used. Where necessary, if the processing specifications are not specified in the prescription, they are used as raw products.

[0032] Particularly preferably, the processed products selected in the present invention are obtained through a large amount of clinical practice and / or pharmacodynamic experiments, and are the best among various processed products of similar Chinese herbal medicines, and can exert the best therapeutic effect on functional dyspepsia.

[0033] The Chinese medicine composition has the effects of pungent and bitter, promoting descending, soothing the liver and strengthening the spleen, regulating qi and harmonizing the stomach. It is used for cold and heat syndrome, liver and stomach disharmony, spleen deficiency and qi stagnation, stomach fullness or distension and pain, poor appetite, fatigue, bitter mouth and dry throat, intestinal rumbling and loose stools, pale tongue with yellow or greasy coating, and stringy and thin pulse; functional dyspepsia with the above symptoms.

[0034] In order to facilitate the explanation of the selection of raw materials and compatibility principles of the Chinese medicine composition, the Chinese medicine composition of the present application is at least based on the following TCM monarch-minister-assistant-adjuvant matching theory when formulating and compatibility: Pinellia ternata is pungent and warm to disperse, Coptis chinensis is bitter and cold to purge heat, and the two are pungent and pungent to clear and descend and eliminate abdominal distension as the monarch medicine. Scutellaria baicalensis is bitter and cold to dry dampness, and dried ginger is pungent and hot to warm the middle as the minister. Codonopsis pilosula nourishes the spleen and lungs; Amomum villosum promotes qi and regulates the middle; Magnolia officinalis and Rhubarb clear the bowels and eliminate accumulation, and promote the movement of qi; Curcuma zedoaria promotes qi and blood circulation, clears the heart and relieves depression; Vinegar and Corydalis enter the liver and nourish blood, and are used together with white peony root to relieve pain and regulate qi and blood; roasted licorice harmonizes all the medicines; ginger and jujube are used together to protect the spleen and stomach and warm and nourish the middle jiao. The combination of all the medicines can not only lift the floating and lighten the body, but also clear the body and descend the adverse, and play the role of pungent and pungent to clear and descend, balance cold and heat, and regulate qi and regulate the middle. It is understandable that in addition to the above-mentioned theory of traditional Chinese medicine formula, the inventors of the present application also conducted a large amount of modern pharmacology and clinical practice research, thereby obtaining the traditional Chinese medicine composition for treating functional dyspepsia described in the present application with the optimal raw material composition and weight ratio.

[0035] Another object of the present invention is to provide a pharmaceutical preparation for treating functional dyspepsia based on the above-mentioned Chinese medicine composition, which can be conveniently used in clinical practice, can ensure the safety of the medicine, is quality-controlled, and can fully exert its therapeutic effect.

[0036] In order to achieve the above object, the technical solution of the present invention is as follows:

[0037] A Chinese medicine preparation for treating functional dyspepsia, which is composed of Chinese medicine ingredients and pharmaceutically acceptable excipients, wherein the Chinese medicine ingredients are prepared from the following Chinese medicine raw materials in parts by weight:

[0038] 6-11 parts of ginger pinellia, 6-11 parts of wine scutellaria, 3-7 parts of wine coptis, 6-11 parts of dried ginger, 6-11 parts of codonopsis pilosula, 3-8 parts of amomum, 2-6 parts of raw rhubarb, 3-11 parts of curcuma, 7-11 parts of magnolia bark, 6-11 parts of stir-fried white peony root, 8-12 parts of vinegar corydalis, 4-9 parts of roasted licorice, and 4-9 parts of jujube.

[0039] In this article, the pharmaceutically acceptable excipients may include any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye / colorant, flavor enhancer, flavoring agent, disintegrant, lubricant, binder, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonic agent, solvent or emulsifier, etc.

[0040] Preferably, the Chinese medicine preparation can be formulated into a solid, semisolid, liquid or gaseous preparation, such as tablets, capsules, powders, granules, ointments, oral liquid preparations, suppositories, injections, inhalants, gels, microspheres and aerosols. Typical routes of administering such medicines or health care compositions include oral, topical, transdermal, inhalation, parenteral, sublingual, oral, rectal, vaginal or intranasal.

[0041] Preferably, the Chinese medicine preparation is an oral preparation, more preferably an oral solid, semisolid or liquid preparation, such as tablets, capsules, powders, granules, oral liquid preparations, gels.

[0042] For the above-mentioned oral preparations, one or more of the following substances may be present: a binder such as carboxymethyl cellulose, ethyl cellulose, cyclodextrin, microcrystalline cellulose, tragacanth gum or gelatin; an excipient such as starch, lactose or dextrin; a disintegrant such as alginic acid, sodium alginate, corn starch, etc.; a lubricant such as magnesium stearate; a glidant such as colloidal silicon dioxide; a sweetener such as sucrose or saccharin; a flavoring such as mint, methyl salicylate or orange flavoring; and a coloring agent, etc.

[0043] In some cases, the Chinese medicine preparation may also be an injection so as to achieve a faster therapeutic effect, or it may be suitable for patients who are not convenient to take the medicine orally.

[0044] Most preferably, the Chinese medicine preparation is a granule, which has the characteristics of long shelf life, high patient acceptance, easy use, and rapid efficacy. In particular, the Chinese medicine preparation is a granule, which can produce better therapeutic effects than other conventional oral solid preparations such as tablets, pills, and capsules due to the characteristics of less auxiliary materials required for the preparation and easier to work in the stomach under the same dosage. In addition, the Chinese medicine granule preparation has a better shelf life and lower auxiliary materials than oral liquid preparations. In other words, it is optimal for the Chinese medicine preparation of the present invention to be selected as a granule.

[0045] Preferably, the excipient of the granules is one or more of lactose, dextrin or soluble starch.

[0046] More preferably, the excipient is dextrin. Preferably, the drug-excipient ratio of the traditional Chinese medicine component to the excipient is 1:1-3:1, preferably 2:1.

[0047] Preferably, when preparing the granules, the wetting agent is ethanol with a concentration of 85-95%, preferably 95%.

[0048] Another object of the present invention is to provide a method for preparing the Chinese medicine preparation, which can effectively enrich the active ingredients in the Chinese medicine raw materials and has the characteristics of simple process, low cost, non-toxicity, and convenient industrial production.

[0049] In order to achieve the above object, the technical solution of the present invention is as follows:

[0050] A method for preparing a traditional Chinese medicine preparation for treating functional dyspepsia comprises the following steps:

[0051] The medicinal materials are weighed according to the weight ratio, extracted, filtered, the filtrates are combined, concentrated, and auxiliary materials are added to prepare the traditional Chinese medicine preparation.

[0052] Preferably, the preparation method comprises the following steps:

[0053] The medicinal materials are weighed according to the weight ratio, decocted in water for extraction, filtered, the filtrates are combined, and concentrated under reduced pressure to obtain a thick paste, the thick paste is dried to obtain a dry paste, and auxiliary materials are added to prepare a traditional Chinese medicine preparation.

[0054] Preferably, the preparation method comprises the following steps:

[0055] Medicinal materials are weighed according to weight ratio, decocted with water for extraction, filtered, the filtrates are combined, and concentrated under reduced pressure to obtain a thick paste, the thick paste is dried to obtain a dry paste, and auxiliary materials are added to prepare a traditional Chinese medicine preparation; wherein the water for decoction is 5-10 times of water, and the extraction is performed 2-4 times, each time for 0.5-2 hours, the medicinal materials are soaked for 0.5-4 hours before extraction, and rhubarb and magnolia bark are added 5-20 minutes before the end of the first extraction; the concentration temperature is controlled at no more than 90°C, and the drying temperature is controlled at no more than 80°C.

[0056] Most preferably, the preparation method comprises the following steps:

[0057] The water used for decoction is 6 times the amount of water, and the extraction is performed twice, each time for 1 hour. The medicinal materials are soaked for half an hour before extraction, and rhubarb and magnolia bark are added 10 minutes before the end of the first extraction. The concentration temperature is controlled at no more than 80°C, and the drying temperature is controlled at no more than 60°C.

[0058] Another object of the present invention is to provide the use of the Chinese medicine composition in the preparation of medicines, which can effectively exert the therapeutic effect of the Chinese medicine composition and has good therapeutic effects on various types of functional dyspepsia.

[0059] In order to achieve the above object, the technical solution of the present invention is as follows:

[0060] A use of a traditional Chinese medicine composition for treating functional dyspepsia in preparing a medicine for treating functional dyspepsia.

[0061] Preferably, the Chinese medicine composition can also be used to prepare a medicine for treating epigastric distension, distending pain, poor appetite, bitter mouth and dry throat, and / or intestinal rumbling and loose stools caused by cold and heat syndrome, liver-stomach disharmony, and / or spleen deficiency and qi stagnation.

[0062] More preferably, the inventors of the present application have unexpectedly found that the Chinese medicine composition can also improve psychiatric symptoms such as anxiety and depression associated with functional dyspepsia. That is, the present invention also provides the use of the Chinese medicine composition for preparing a drug for treating psychiatric symptoms associated with functional dyspepsia. Further, the psychiatric symptom is anxiety or depression associated with functional dyspepsia.

[0063] Therefore, compared with the prior art, the advantages of the present invention are:

[0064] 1. Compared with the basic recipe of Banxia Xiexin Decoction, the present invention can better treat functional dyspepsia by adding targeted Chinese medicinal raw materials, and the therapeutic effect is significantly increased.

[0065] 2. Compared with the Weikangning prescription published by the inventor in 1994, namely, scutellaria baicalensis, dried ginger, codonopsis pilosula, vinegar-corydalis, curcuma aromatica, magnolia bark, white peony root, rhubarb, ginger pinellia, coptis chinensis, and amomum villosum, the present invention further optimizes the processed varieties of scutellaria baicalensis, coptis chinensis, rhubarb and white peony root, adds roasted licorice and jujube, and adjusts and determines the weight ratio of Chinese medicinal raw materials, and has achieved remarkable technical progress through years of exploration and research. The technical progress specifically relates to improved efficacy, reduced side effects, and increased patient compliance.

[0066] 3. The present invention is relative to the Weikangning prescription published by the inventor in 2010, i.e., 9g of Scutellaria baicalensis, 9g of dried ginger, 15g of Codonopsis pilosula, 18g of Curcuma aromatica, 10g of Magnolia officinalis, 15g of White Peony Root, 10g of Corydalis yanhusuo, 9g of Bupleurum chinense, 6g of Rhubarb, 9g of Radix Glycyrrhizae Preparata, 4 pieces of jujube are decocted, extracted, filtered, concentrated into paste, dried, and equal amounts of Pinellia ternata, Coptis chinensis, and Fructus Amomi are dried and powdered, sieved through an 80-mesh sieve, and mixed and packed into capsules. After further clinical practice research, the present invention further optimizes the processed varieties of Scutellaria baicalensis, Coptis chinensis, Rhubarb, and White Peony Root, simplifies Bupleurum chinense, clarifies the dosage of Pinellia ternata, Coptis chinensis, and Fructus Amomi, and reduces the dosage of Codonopsis pilosula, Curcuma aromatica, Magnolia officinalis, White Peony Root, Rhubarb, and Licorice, so that the prescription is streamlined as a whole, and a better effect of treating functional dyspepsia can be achieved with less crude drug dosage.

[0067] 4. The present invention has found the optimal weight ratio based on clinical practice, so that the compatibility of the main, secondary, adjuvant and guiding ingredients in the entire prescription is reasonable and the optimal therapeutic effect is achieved.

[0068] 5. Through pharmaceutical research, the present invention has found the most suitable preparation type and preparation method for the present invention, which can maximize the therapeutic effect of the Chinese medicine composition of the present invention and meet production needs. BRIEF DESCRIPTION OF THE DRAWINGS

[0069] Figure 1The effect of the Chinese medicine composition of the present invention on gastric sensitivity of FD rats. Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001; compared with the model group, #P<0.05, ##P<0.01, ###P<0.001.

[0070] Figure 2 The effect of the Chinese medicine composition of the present invention on gastric emptying of FD model rats. Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001; compared with the model group, #P<0.05, ##P<0.01, ###P<0.001.

[0071] Figure 3 The effect of the Chinese medicine composition of the present invention on the depressive behavior of FD model rats. Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001; compared with the model group, #P<0.05, ##P<0.01, ###P<0.001.

[0072] Figure 4 The effect of the Chinese medicine composition of the present invention on CCK and MTL in gastric tissue of FD model rats, wherein Figure 4-1 The impact on CCK, Figure 4-2 It is the impact on MTL.

[0073] Figure 5 This is the chromatogram of baicalin. A: reference solution; B: test solution; C: negative test solution; the chromatographic peak 1 in the figure is baicalin.

[0074] Figure 6 This is a graph showing the results of the linear relationship investigation of baicalin.

[0075] Figure 7 It is the moisture absorption percentage curve. DETAILED DESCRIPTION

[0076] The present invention is further described below by specific examples, and the present invention is not limited to the following examples. Within the scope of the present invention or without departing from the content, spirit and scope of the present invention, the changes, combinations or substitutions made to the present invention are obvious to those skilled in the art and are included in the scope of the present invention.

[0077] Embodiment 1:

[0078] A Chinese medicine composition for treating functional dyspepsia is prepared from the following Chinese medicine raw materials in parts by weight:

[0079] Ginger Pinellia 9g, wine Scutellaria 9g, wine Coptis chinensis 5g, dried ginger 9g, Codonopsis pilosula 9g, Amomum villosum 6g, raw rhubarb 3g, Curcuma 9g, Magnolia officinalis 9g, stir-fried white peony root 9g, vinegar Corydalis 10g, roasted licorice root 6g, and jujube 6g.

[0080] Embodiment 2:

[0081] A Chinese medicine composition for treating functional dyspepsia is prepared from the following Chinese medicine raw materials in parts by weight:

[0082] 11g of Pinellia ternata with ginger, 11g of Scutellaria baicalensis with wine, 7g of Coptis chinensis with wine, 11g of dried ginger, 11g of Codonopsis pilosula, 4g of Amomum villosum, 2g of raw rhubarb, 7g of Curcuma aromatica, 7g of Magnolia officinalis, 7g of stir-fried white peony root, 8g of Corydalis yanhusuo with vinegar, 4g of roasted licorice root, and 4g of jujube.

[0083] Embodiment 3:

[0084] A Chinese medicine composition for treating functional dyspepsia is prepared from the following Chinese medicine raw materials in parts by weight:

[0085] Ginger Pinellia 7g, wine Scutellaria 7g, wine Coptis chinensis 3g, dried ginger 7g, Codonopsis pilosula 7g, Amomum villosum 8g, raw rhubarb 4g, Curcuma 11g, Magnolia officinalis 11g, stir-fried white peony root 11g, vinegar Corydalis 12g, roasted liquorice root 8g, jujube 8g.

[0086] Embodiment 4:

[0087] A Chinese medicine composition for treating functional dyspepsia is prepared from the following Chinese medicine raw materials in parts by weight:

[0088] 11g of Pinellia ternata with ginger, 11g of Scutellaria baicalensis with wine, 7g of Coptis chinensis with wine, 11g of dried ginger, 6g of Codonopsis pilosula, 3g of Amomum villosum, 2g of raw rhubarb, 3g of Curcuma aromatica, 7g of Magnolia officinalis, 11g of stir-fried white peony root, 8g of Corydalis yanhusuo with vinegar, 4g of roasted licorice root, and 4g of jujube.

[0089] Embodiment 5:

[0090] A Chinese medicine composition for treating functional dyspepsia is prepared from the following Chinese medicine raw materials in parts by weight:

[0091] Ginger Pinellia 6g, wine Scutellaria 6g, wine Coptis chinensis 3g, dried ginger 6g, Codonopsis pilosula 11g, Amomum villosum 8g, raw rhubarb 6g, Curcuma 11g, Magnolia officinalis 11g, stir-fried white peony root 6g, vinegar Corydalis 12g, roasted liquorice root 9g, jujube 9g.

[0092] Embodiment 6:

[0093] The medicinal materials were weighed according to the weight ratio of Example 1, and decocted in water for extraction. The decoction condition was 6 times of water. The extraction was performed twice, each time for 1 hour. The medicinal materials were soaked for 0.5 hour before extraction. Rhubarb and Magnolia officinalis were added 10 minutes before the end of the first extraction. After each extraction, the filtrates were combined and concentrated under reduced pressure at no more than 80°C to obtain a thick paste. The thick paste was dried at a temperature of no more than 60°C to obtain a dry paste. The dry paste was crushed, dextrin was added according to the drug-excipient ratio of 2:1 based on the amount of the dry paste, and 95% ethanol was used as a wetting agent to prepare granules.

[0094] Embodiment 7:

[0095] The medicinal materials were weighed according to the weight ratio of Example 1, and decocted in water for extraction. The decoction condition was 5 times the amount of water, and the extraction was performed 4 times, each time for 0.5 hour. The medicinal materials were refrigerated for 4 and a half hours before extraction. Rhubarb and Magnolia officinalis were added 20 minutes before the end of the first extraction. After each extraction, the filtrates were combined and concentrated under reduced pressure at a temperature not higher than 90°C to obtain a thick paste. The thick paste was spray-dried at a temperature not higher than 80°C to obtain a dry paste powder, dextrin was added, and lactose was added according to the drug-excipient ratio of 3:1 based on the amount of dry paste. 85% ethanol was used as a wetting agent to prepare granules, which were loaded into capsules to prepare capsules.

[0096] Embodiment 8:

[0097] The medicinal materials were weighed according to the weight ratio of Example 1, and decocted in water for extraction. The decoction condition was 10 times the water. The extraction was performed 3 times, each time for 2 hours. The medicinal materials were pre-fermented for 1.5 hours before extraction. Rhubarb and Magnolia officinalis were added 5 minutes before the end of the first extraction. After each extraction, the filtrates were combined and concentrated under reduced pressure at a temperature not higher than 85°C to obtain a thick paste. The thick paste was dried at a temperature not higher than 70°C to obtain a dry paste. The dry paste was crushed, and soluble starch was added according to a drug-excipient ratio of 1:1 based on the amount of the dry paste. 90% ethanol was used as a wetting agent to prepare granules. Magnesium stearate and microcrystalline cellulose were added and tablets were prepared.

[0098] Example 9

[0099] The medicinal materials were weighed according to the weight ratio of Example 2, and ethanol was refluxed for extraction. The decoction condition was 10 times the solvent, and the extraction was performed twice, each time for 1 hour. The medicinal materials were soaked for 0.5 hour before extraction, and rhubarb and magnolia bark were added 10 minutes before the end of the first extraction; after each extraction, the filtrates were combined and concentrated under reduced pressure at no more than 80°C to obtain a thick paste, the thick paste was dried at a temperature of no more than 60°C to obtain a dry paste, the dry paste was crushed, and dextrin was added according to the drug-excipient ratio of 2:1 based on the amount of the dry paste to prepare granules.

[0100] Example 10

[0101] The medicinal materials were weighed according to the weight ratio of Example 2, and ethanol was refluxed for extraction. The decoction condition was 10 times the solvent, and the extraction was performed twice, each time for 1 hour. The medicinal materials were soaked for 0.5 hour before extraction, and rhubarb and magnolia bark were added 10 minutes before the end of the first extraction; after each extraction, the filtrates were combined and concentrated under reduced pressure at no more than 80° C. to obtain a thick paste, the thick paste was dried at a temperature no more than 60° C. to obtain a dry paste, and the dry paste was crushed to prepare an orally disintegrating tablet.

[0102] Embodiment 11

[0103] The medicinal materials were weighed according to the weight ratio of Example 2, extracted with 50% ethanol under reflux, the decoction condition was 8 times the solvent, extracted 3 times, each time for 1.5 hours, the medicinal materials were soaked for 0.5 hours before extraction, and rhubarb and magnolia bark were added 10 minutes before the end of the first extraction; after each extraction, the filtrates were combined, and concentrated under reduced pressure at no more than 80° C. to obtain a fluid extract, and a flavoring agent was added to prepare an oral liquid preparation.

[0104] Example 12 (Pharmacodynamics Experiment)

[0105] The FD rat model was constructed using the classic iodoacetamide modeling method (see "1.6 Iodoacetamide Modeling Method" recorded in "Fan Mingming, Zhang Jiayu, et al. Review of Functional Dyspepsia Modeling Methods [J]. World Traditional Chinese Medicine, 2020, 15(07): 1080-1083"). The study found that the Chinese medicine composition of the present invention (ie, Example 1) can significantly reduce gastric hypersensitivity in FD model rats, increase gastric emptying, and significantly improve the depressive state. It has a significant regulatory effect on the brain gut peptides CCK and MTL involved in regulating appetite and gastric motility in the gastric tissue of FD model rats. Through the results of cytotoxicity experiments and HPLC analysis, molecular experimental studies were carried out using crude Chinese medicine extracts with stable components. The results showed that the Chinese medicine composition of the present invention can induce the expression of GSTP1 and SOD2 through the Nrf2 / ARE pathway in gastric epithelial cells (GSE-1), thereby exerting a protective effect on gastric mucosal epithelial cells. Furthermore, through in vivo experiments on FD animals, it was found that the Chinese medicine composition of the present invention has a significant reducing effect on the lipid peroxide product MDA, confirming the antioxidant effect of the Chinese medicine composition of the present invention. Through metabolomics, it was found that the Chinese medicine composition of the present invention may regulate metabolic disorders by affecting multiple metabolic pathways such as energy metabolism, stress-related metabolism and intestinal flora, thereby playing a therapeutic role in FD. Through brain functional nuclear magnetic resonance detection technology, it was found that the Chinese medicine composition of the present invention has a regulatory effect on the basolateral nucleus, anterior cingulate gyrus, prefrontal lobe and other brain areas related to pain and emotion. The preliminary clinical and basic data provide strong support for the treatment of FD with the Chinese medicine composition of the present invention.

[0106] 1) Evaluation of intervention effects on gastric sensitivity, gastric emptying and behavior in FD model rats

[0107] Gastric sensitivity: Studies have shown that the Chinese medicine composition of the present invention can significantly alleviate gastric hypersensitivity in FD model rats. Under pressures of 40 mmHg, 60 mmHg, and 80 mmHg, the root mean square change rate of electromyogram (EMG) in the Chinese medicine composition group was significantly reduced compared with the model group (P < 0.05, P < 0.05, P < 0.001). Figure 1 .

[0108] Gastric emptying rate: After intervention, the gastric emptying rate of the Chinese medicine composition group and the mosapride group increased compared with the model group, and the difference was statistically significant (all P < 0.05), and the effect of the Chinese medicine composition group of the present invention was equivalent to that of the mosapride group (P > 0.05). Figure 2 .

[0109] Behavioral effects: The Chinese medicine composition of the present invention can significantly improve the depressive-like behavior of FD model rats. The results of the forced swimming test showed that the immobility time of the Chinese medicine composition group was reduced compared with the model group, and the difference was statistically significant (P < 0.05). Figure 3 .

[0110] Effect of the Chinese medicine composition of the present invention on brain gut peptide CCK and MTL in FD model rats: After intervention, compared with the model group, the gastric tissue CCK of the medium-dose and high-dose groups of the Chinese medicine composition of the present invention was significantly reduced, and the MTL was significantly increased, and the differences were statistically significant (all P < 0.05), indicating that the Chinese medicine composition of the present invention has a certain effect of regulating appetite and promoting gastric motility. Figure 4 .

[0111] Effect of the Chinese medicine composition of the present invention on the metabolomics of FD model rats. During the replication of the stress FD model, the disturbance of endogenous metabolic information mainly affects the metabolic pathways involved: phenylalanine, tyrosine and tryptophan biosynthesis, citric acid cycle, phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, glyoxylate and dicarboxylic acid metabolism and tyrosine metabolism. During the intervention of the Chinese medicine composition of the present invention in FD, the metabolic pathways involved in the changes in the endogenous metabolic information network are: glyoxylate and dicarboxylic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glycine, serine and threonine metabolism, phenylalanine metabolism, valine, leucine and isoleucine biosynthesis and glyceride metabolism. The results show that the Chinese medicine composition of the present invention may regulate metabolic disorders by affecting multiple metabolic pathways such as energy metabolism, stress-related metabolism and intestinal flora, thereby playing a therapeutic role in FD.

[0112] Example 13 (Clinical Experiment)

[0113] The team of Professor Wei Wei, the inventor of the present application, has formed a fixed prescription for treating FD - the Chinese medicine composition of the present invention in 35 years of clinical practice, and has conducted relevant research on the clinical efficacy and drug mechanism of the Chinese medicine composition of the present invention in treating FD.

[0114] A randomized, double-blind, placebo-controlled clinical trial method was used to observe the clinical efficacy and safety of the Chinese medicine composition of the present invention in treating FD patients from the aspects of clinical symptoms, psychological evaluation, gastrointestinal motility and safety examination, and objectively evaluate the clinical efficacy and safety of the Chinese medicine composition of the present invention in treating FD. The results showed that after the FD patients were treated with the Chinese medicine composition of the present invention, the treatment group was better than the control group in the evaluation of the efficacy of Chinese medicine syndrome and the evaluation of the efficacy of Western medicine symptoms, and no adverse reactions occurred in the two groups in the safety evaluation. The treatment group used the granules of Example 6, and the control group used mosapride.

[0115] (1) Comparison of TCM symptom effectiveness

[0116] Table 1 Comparison of the effectiveness of TCM symptoms after 4 weeks of treatment

[0117] Group Number of cases Significant effect efficient invalid Effectiveness% Treatment Group 70 10 56 4 94.3 Control group 32 8 14 10 62.5

[0118] Compared with the control group, P<0.05.

[0119] The sample rates of the two groups were compared using the χ2 test. Compared with the control group, the treatment group had a higher effective rate, P=0.01 (P<0.05), which was statistically significant, that is, after 4 weeks of treatment, the effective rate of TCM symptoms in the treatment group was better than that in the placebo control group.

[0120] (2) Comparison of the effectiveness of Western medicine symptoms

[0121] Table 2 Comparison of the effectiveness of Western medicine symptoms after 4 weeks of treatment

[0122] Group Number of cases Significant effect efficient invalid Effectiveness% Treatment Group 70 29 37 4 94.3 Control group 32 3 19 10 68.7

[0123] Compared with the control group, P<0.05.

[0124] The sample rates of the two groups were compared using the χ2 test. Compared with the control group, the treatment group had a higher effective rate, P=0.00 (P<0.05). The difference was statistically significant, that is, after 4 weeks of treatment, the effective rate of Western medicine symptoms in the treatment group was better than that in the placebo control group.

[0125] (3) Comparison of gastric emptying rate

[0126] Table 3 Comparison of gastric emptying in the treatment groups before and after treatment

[0127]

[0128] The data of the two groups were in accordance with normal distribution and homogeneity of variance. Paired t-test was used, t=-10.9, p=0.00 (P<0.05). The gastric emptying rate of the treatment group after treatment was higher than that before treatment, and the difference was statistically significant.

[0129] Table 4 Comparison of gastric emptying in the control group before and after treatment

[0130]

[0131] The data of the two groups were in accordance with normal distribution and homogeneity of variance. Paired t-test was used, t=4.23, p=0.00 (P<0.05). The gastric emptying rate of the control group after treatment was higher than that before treatment, and the difference was significant.

[0132] Table 5 Comparison of the difference in gastric emptying rate between the treatment group and the control group before and after treatment

[0133]

[0134] The differences in gastric emptying rates before and after treatment were compared between the treatment group and the control group. The data of the two groups were normal and had homogeneous variances. The t-test was used, T=1.37, P=0.18 (P>0.05), indicating that there was no statistically significant difference in the difference in gastric emptying rates before and after treatment between the treatment group and the control group.

[0135] Correlation analysis of gastric emptying rate

[0136] A correlation analysis was performed between the gastric emptying rate before treatment and height, weight, age, gender, total score of TCM symptoms, total score of Western medicine symptoms, and single TCM symptom score and single Western medicine symptom score. It was found that the gastric emptying rate before treatment was not correlated with height, weight, age, gender, or the total score of TCM symptoms, but was positively correlated with the TCM epigastric or abdominal distension symptom score (r=0.209, P=0.03) and the acid reflux symptom score (r=0.192, P=0.05). Gastric emptying was positively correlated with the total score of Western medicine symptoms (r=0.176, P=0.03) and the "postprandial fullness" symptom score (r=0.237, P=0.02).

[0137] (4) Improvement in mental and psychological status

[0138] Comparison of SAS, SDS scores, TCM syndrome scores, and Western medicine symptom scores between the two groups before and after treatment

[0139] After treatment, the anxiety, depression scores and clinical symptom scores of 102 FD patients in both groups decreased. The P value was <0.01, which was significantly different; the P value was <0.05, which was statistically different. The comparison showed that both the therapeutic drug and the placebo could improve the patients' mental and psychological state and clinical symptoms, and the therapeutic effect of the treatment group was more significant.

[0140] Table 6 Comparison of SAS, SDS scores, TCM syndrome scores, and Western medicine symptom scores between the two groups before and after treatment

[0141]

[0142]

[0143] Correlation analysis between clinical symptoms and mental status in 102 patients with FD

[0144] ①Correlation analysis between TCM syndrome scores, Western medicine symptom scores and SAS scores in 102 FD patients

[0145] After testing, the P values ​​were 0.0004 and 0.0003 < 0.01, and the correlation coefficients r were 0.453 and 0.472, respectively, indicating that the clinical symptoms of FD patients were positively correlated with the anxiety scores, that is, the more obvious the clinical symptoms, the more severe the anxiety level.

[0146] ②Correlation analysis between TCM syndrome scores, Western medicine symptom scores and SDS scores in 102 FD patients

[0147] After testing, the P values ​​were 0.0002 and 0.0004<0.01, and the correlation coefficients r were 0.467 and 0.489, respectively, indicating that the clinical symptoms of FD patients were positively correlated with the depression scores, that is, the more obvious the clinical symptoms, the more severe the depression.

[0148] Table 7 Correlation analysis between TCM and Western medicine symptom scores and SAS and SDS scores in 102 FD patients

[0149] Correlation coefficient r P-value SAS score and TCM syndrome score 0.453 0.000 SAS score and Western medicine symptom score 0.472 0.000 SDS score and TCM syndrome score 0.467 0.000 SDS score and Western medicine symptom score 0.489 0.000

[0150] (5) Safety evaluation

[0151] No obvious adverse reactions occurred in the two groups of patients during the entire intervention process. The 102 patients who completed clinical observation had no abnormalities in blood routine, urine routine, stool routine plus occult blood, erythrocyte sedimentation rate, liver function (ALT, AST), renal function (BUN, CRE) and electrocardiogram before treatment and 4 weeks after treatment.

[0152] Experimental Example 1: Drug substance composition and ratio screening experiment

[0153] The rat animal experiment is adopted to prove that the raw material drug combination and ratio of the present application are optimal. Similar animal experiments in the above-mentioned pharmacodynamic experiments can be adopted.

[0154] 1. Animals

[0155] 5-day-old suckling rats were adaptively fed for 5 days, and 7 rats were randomly selected as the blank group. The other rats were prepared with the classic iodoacetamide gavage method to prepare the FD model (see "1.6 iodoacetamide modeling method" recorded in "Fan Mingming, Zhang Jiayu, et al. Review of functional dyspepsia modeling methods [J]. World Chinese Medicine, 2020, 15(07): 1080-1083"), that is, from the 10th day of age, 0.2 ml of a mixture of 0.1% iodoacetamide and 2% sucrose was gavaged once a day for 6 days, and then fed normally (the normal group was given 0.2 ml of 2% sucrose solution by gavage once a day for 6 days, and the other feeding conditions were the same). The model was completed at the 8th week of rats.

[0156] 2. Drugs and groups

[0157] In addition to the blank group and the model group, the following animal groups were also set up:

[0158] 1) Example 1 group;

[0159] 2) Example 2 group;

[0160] 3) Example 3 group;

[0161] 4) The different processed product groups of Example 1, i.e., scutellaria baicalensis, coptis chinensis, and white peony root are raw products, and rhubarb is wine rhubarb;

[0162] 5) Basic prescription group: Pinellia tuber, dried ginger, scutellaria baicalensis 10g each, coptis root 8g, codonopsis pilosula 12g, roasted liquorice root 6g, jujube 12g;

[0163] 6) Prior art group 1, i.e., multi-Bupleurum group (experimental study on the effect of pungent opening and bitter descending method on plasma NO, gastric body NOS ICC and SMC in FD rats); i.e., 9g of Scutellaria baicalensis, 9g of dried ginger, 15g of Codonopsis pilosula, 18g of Curcuma aromatica, 10g of Magnolia officinalis, 15g of White Peony Root, 10g of Corydalis yanhusuo, 9g of Bupleurum chinense, 6g of Sichuan Rhubarb, 9g of Roasted Licorice Root, 4 pieces of jujube were decocted, extracted, filtered, concentrated into paste, and dried, 9g of Pinellia ternata, 5g of Coptis chinensis, and 6g of Amomum villosum;

[0164] 7) Prior art group 2, i.e., a group lacking licorice and jujube (according to the proportions of Example 1, but without licorice and jujube);

[0165] 8) 3 groups of prior art, i.e. CN201810938207 group: Pinellia 10g, Coptis chinensis 8g, Scutellaria baicalensis 9g, Dry ginger 9g, Codonopsis pilosula 15g, Magnolia officinalis 10g, Bupleurum 9g, Curcuma 18g, White Peony 15g, Vinegar Corydalis 10g, Roasted Licorice 9g, Jujube 4g;

[0166] 9) Four prior art groups, i.e., more Bupleurum and Apricot Kernel group (Evaluation of the effect and safety of the method of pungent opening and bitter descending in the treatment of functional dyspepsia): 9g of Pinellia ternata, 5g of Coptis chinensis, 6g of Amomum villosum, 9g of Scutellaria baicalensis, 9g of Dry Ginger, 15g of Codonopsis pilosula, 9g of Curcuma aromatica, 9g of Magnolia officinalis, 15g of White Peony Root, 10g of Vinegar Corydalis, 9g of Bupleurum chinense, 6g of Rhubarb, 9g of Stir-fried Apricot Kernel, 9g of Roasted Licorice Root, and 4 pieces of Jujube;

[0167] 10) Group 1 with different weight ratios: 9g of ginger pinellia, 9g of wine scutellaria, 15g of wine coptis, 9g of dried ginger, 20g of codonopsis pilosula, 6g of amomum, 10g of raw rhubarb, 15g of curcuma, 20g of magnolia bark, 20g of stir-fried white peony root, 10g of vinegar corydalis, 18g of roasted liquorice, and 9g of jujube.

[0168] 11) Group 2 with different weight ratios: 20g of ginger pinellia, 20g of wine scutellaria, 5g of wine coptis, 9g of dried ginger, 5g of codonopsis pilosula, 9g of amomum, 1g of raw rhubarb, 9g of turmeric, 4g of magnolia bark, 5g of stir-fried white peony root, 5g of vinegar corydalis, 3g of roasted liquorice, and 3g of jujube.

[0169] The raw materials of the above groups were prepared into granules according to the method of Example 6, and formulated into suspensions with distilled water.

[0170] 3. Drug administration and testing

[0171] 1) The daily gavage volume of Chinese medicine decoction was calculated by multiplying the human dose by the conversion factor of 0.018 between humans and mice. A blank group and a model group were set up, with 7 mice in the blank group and 7 mice in the model group. The normal group and the model group were gavaged with 0.5ml / 100g of distilled water for 14 days, twice a day.

[0172] 2) Gastric emptying test

[0173] After 14 days of intervention, rats in each group were fasted but not watered for 24 hours. After the fasting period, each rat was housed in a single cage and given 2 g of dry feed to be eaten within 10 minutes. The rat was killed after 90 minutes of timing, the entire stomach tissue was removed, and the tissue was cut open along the lesser curvature of the stomach. The stomach contents were placed on clean filter paper as much as possible. Each filter paper was weighed in advance. The stomach contents on the filter paper were weighed after they were completely dried, and then the gastric emptying rate was calculated. Gastric emptying rate (%) = (2 g - dry stomach content weight) / 2 g × 100%.

[0174] 4. Results

[0175] The gastric emptying rate of the model group rats was lower than that of the blank group, and the difference was statistically significant (P < 0.01). Compared with the model group, the gastric emptying of FD rats was significantly improved after Chinese medicine intervention (all P < 0.01), and group 1 > group 2 and group 3 > group 4 > group 6 > group 9 > group 10 and group 11 > group 7 > group 8 > group 5 (Table 8).

[0176] Table 8 Comparison of gastric emptying rate of rats in each group after intervention

[0177] Grouping n Gastric emptying rate (%) Normal group 7 75.71±15.01 Model Group 7 <![CDATA[39.33±14.32 ** ]]> 1 group 7 <![CDATA[74.57±19.47 ## ]]> 2 groups 7 <![CDATA[71.36±20.68 ## ]]> 3 groups 7 <![CDATA[71.48±17.72 ## ]]> 4 groups 7 <![CDATA[69.15±16.18 ## <!-- 13 -->]]> 5 groups 7 <![CDATA[57.32±17.63 ## ]]> 6 groups 7 <![CDATA[68.79±16.35 ## ]]> 7 groups 7 <![CDATA[62.24±16.93 ## ]]> 8 groups 7 <![CDATA[61.06±16.25 ## ]]> 9 groups 7 <![CDATA[67.97±17.49 ## ]]> 10 groups 7 <![CDATA[65.80±16.61 ## ]]> 11 groups 7 <![CDATA[66.39±18.20 ## ]]>

[0178] Note: Compared with the normal group, ** P<0.01; compared with the model group, ## P<0.01.

[0179] The results of the above experiments illustrate that: 1) From the results that group 1-3 is better than group 5, it can be seen that the technical solution of the present invention is significantly better than the basic recipe of Banxia Xiexin, and the present application has achieved significant technical progress after increasing the raw materials and challenging the dosage configuration; 2) From the results that group 1-3 is better than group 4, it can be seen that the selection of the processed products of the present application has improved the efficacy to a certain extent, and the relevant processed products are more suitable for the treatment of functional dyspepsia; 3) From the results that group 1-3 is better than group 10-11, it can be seen that the weight configuration of the present application is preferred, which is better than the technical solution with the same raw materials but different weight configurations; 4) From the results that group 1-3 is better than group 6-9, it can be seen that the raw material combination of the present application has achieved the most reasonable formula and the highest efficacy, which is better than the technical solutions already disclosed in the prior art; 5) From the results that group 1 is better than group 2-3, it can be seen that the weight ratio of Example 1 is the best, in fact, the most preferred technical solution.

[0180] Experimental Example 2: Preparation Process Screening Experiment Based on the previous comparative study of different dosage forms such as granules, tablets, and capsules, the inventors found that granules are the preferred dosage form, which is better than tablets and capsules. Similarly, water extraction is the preferred extraction process, which is better than ethanol extraction and direct crushing for medicine.

[0181] 1. Investigation of water extraction process

[0182] (1) Instruments and reagents

[0183] ① Medicinal materials and medicines

[0184] Pinellia tuber with ginger (batch number 21051703; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), Scutellaria baicalensis with wine (batch number 19092102; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), Coptis chinensis with wine (batch number 19062602; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), dried ginger (batch number 21031502; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), Codonopsis pilosula (batch number 21052101; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), stir-fried Amomum villosum (batch number 20122401; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), Rhubarb (batch number 20121804; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), ; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), Curcuma (Batch No. 21032001; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), Magnolia officinalis (Batch No. 21062201; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), Stir-fried White Peony Root (Batch No. 20111403; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), Vinegar Corydalis (Batch No. 21041501; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), Roasted Licorice (Batch No. 20112402; Beijing Sifang Chinese Medicine Pieces Co., Ltd.), Jujube (Batch No. 20120801; Beijing Sifang Chinese Medicine Pieces Co., Ltd.)

[0185] Baicalin (batch number 110715-202122; content 94.2%; China Food and Drug Inspection Institute), epiberberine (batch number 10198; content 99.1%; Shanghai Stand Standard Technical Services Co., Ltd.), coptisine hydrochloride (batch number 112026-201802; content 94.0%; China Food and Drug Inspection Institute), palmatine hydrochloride (batch number 110732-201913; content 85.7%; China Food and Drug Inspection Institute), berberine hydrochloride (batch number 110713-202015; content 85.9%; China Food and Drug Inspection Institute)

[0186] ②Reagents

[0187] Acetonitrile (chromatographic grade, Fisher); methanol (chromatographic grade, Fisher); phosphoric acid (batch number: 20180605, Beijing Chemical Plant); Wahaha purified water; deionized water; ethanol (95%) (Tianjin Zhiyuan Chemical Reagent Co., Ltd.).

[0188] ③Instrument

[0189] High performance liquid chromatography (LC-20AT, Shimadzu Corporation, Japan);

[0190] 0.01 mg electronic balance (MS105DU, Mettler-Toledo GmbH);

[0191] 0.01 g electronic balance (YP5002, Shanghai Youke Instrument Co., Ltd.);

[0192] Temperature-adjustable electric heating mantle (ZDHM type, Beijing Zhongxing Weiye Instrument Co., Ltd.);

[0193] Ultrasonic cleaner (SB-5200, Ningbo Xinzhi Technology Co., Ltd.);

[0194] Electric constant temperature water bath (HH-S8, Beijing Kewei Yongxing Instrument Co., Ltd.);

[0195] Blast drying oven (DHG-9145A, Shanghai Yiheng Scientific Instrument Co., Ltd.);

[0196] High-speed universal pulverizer (Model FW-200, Beijing Kewei Yongxing Instrument Co., Ltd.).

[0197] (2) Content determination method

[0198] ① Determination method of content of index components

[0199] Taking baicalin as the indicator ingredient, a content determination method was established with reference to Volume 1 of the 2020 edition of the Chinese Pharmacopoeia.

[0200] Preparation of reference solution:

[0201] Baicalin: Take an appropriate amount of baicalin reference substance, weigh it accurately, and add methanol to prepare a reference substance solution with a baicalin concentration of 609.66 μg / mL.

[0202] Preparation of water extract test solution: Take the prescribed amount of medicinal materials, heat and reflux extraction according to the decoction method of the prescription, and combine the filtrate for detection. The result of the determination of baicalin content in the Radix Scutellariae used in this experiment is: 142.4121 mg·g -1 .

[0203] Chromatographic conditions:

[0204] Baicalin: Agilent Zorbax SB-C18 (5 μm, 4.6×250 nm), the instrument was Shimadzu LC-20AT high performance liquid chromatograph, the mobile phase was methanol-0.1% phosphoric acid aqueous solution (40:60), the column temperature was 40°C, the detection wavelength was 280 nm, the flow rate was 1.0 mL / min, and the injection volume was 10 μL.

[0205] a. Exclusivity

[0206] The chromatograms of the aqueous extract sample solution of the Chinese medicine composition of the present invention, the baicalin reference solution, and the scutellaria negative test sample were prepared respectively. The results are shown in Figure 5 .

[0207] Results: The specificity of the determination method for baicalin and the four alkaloids was good and met the determination requirements.

[0208] b. Linear relationship

[0209] Investigation on the linear relationship of baicalin

[0210] Accurately weigh an appropriate amount of baicalin standard, dissolve it in methanol, and make up to volume. Dilute it in multiples to obtain a series of mixed solutions, and inject it for determination. Perform linear regression with the injected mass concentration as the horizontal axis (X, mg / mL) and the peak area as the vertical axis (Y). The results are shown in Figure 6 .

[0211] Results: The linear relationship of baicalin in the range of 0.18908 to 0.94539 mg / mL met the determination requirements well.

[0212] c. Precision

[0213] The baicalin standard solution was prepared, and the determination was repeated 6 times continuously to calculate the peak area RSD value. The results are shown in Table 9.

[0214] Table 9 Precision investigation results

[0215] Baicalin 1 24778815 2 24736928 3 24712575 4 24735028 5 24804597 6 24759306 RSD(%) 0.13

[0216] Results: The peak area RSD values ​​of the index components were all less than 3%, indicating that the instrument had good precision.

[0217] d. Repeatability

[0218] The aqueous extract of the Chinese medicine composition of the present application was prepared, and the measurement was repeated 6 times continuously to calculate the RSD value of the peak area. The results are shown in Table 10.

[0219] Table 10 Repeatability test results

[0220]

[0221]

[0222] Results: The RSD values ​​of the peak areas of the index components were all less than 3%, indicating that the method had good repeatability.

[0223] e. Stability

[0224] The aqueous extract solution of the Chinese medicine composition of the present application was prepared, and the samples were injected and measured at 0, 2, 4, 6, 12, and 24 hours respectively. The peak area RSD values ​​of the three index components in the Sichen granule test sample within 24 hours were calculated. The results are shown in Table 11.

[0225] Table 11 Stability test results

[0226] Time (h) Baicalin 0 48.39 2 48.27 4 48.41 6 48.22 12 48.08 24 48.19 RSD(%) 0.24

[0227] Results: The peak area RSD values ​​of the index components were all less than 3% within 24 hours, indicating that the samples were stable within 24 hours and met the determination requirements.

[0228] (3) Extraction process investigation

[0229] The extraction rate of baicalin extracted from the drug solution by the prescription method was used as the investigation index, and the paste yield and alcohol extract were used as reference indicators. The relevant indicators of the drug solution prepared by the prescription method were compared. The amount of water added (A), extraction time (B), and extraction times (C) were used as influencing factors. The L9(3 4 ) Orthogonal test to optimize the extraction process. The factor level table is shown in Table 12.

[0230] Table 12 Orthogonal factor level table

[0231]

[0232]

[0233] (4) Orthogonal experimental results and variance analysis

[0234] Weigh 9 portions of medicinal materials according to the prescription ratio, add water for reflux extraction according to the orthogonal test table, filter, combine the filtrate, dilute to an appropriate volume, shake well, filter and sample for testing. Record the peak area of ​​baicalin, calculate the extraction amount, and calculate the extraction rate of baicalin according to formula (1).

[0235] Take 400 or 500 ml of the water extract obtained in the orthogonal experiment, concentrate under reduced pressure at 60°C, pour into a weighed, dry and clean evaporating dish, dry under vacuum at 60°C, weigh again and calculate the paste rate according to formula (2).

[0236] The dry ointment obtained by taking out the ointment rate was tested according to the extract determination method in General Chapter 2201 of the 2020 edition of the Chinese Pharmacopoeia.

[0237] Each group of experiments was carried out twice in parallel, and the mean of the two experimental results was calculated. The data were processed using SPSS software to screen out the best extraction process.

[0238] The results of the prescription method analysis, orthogonal test and variance analysis are shown in Tables 13-15.

[0239]

[0240]

[0241] Table 13 Preparation results of prescription method

[0242] Baicalin extraction rate (%) Cream yield (%) Alcohol extract (%) 1 41.36 25.86 45.88 2 42.89 26.45 46.86 3 35.55 27.04 47.87 average value 39.94 26.54 46.87

[0243] Table 14 Orthogonal experiment intuitive analysis table (with baicalin extraction rate as an indicator, n = 2)

[0244]

[0245]

[0246] Table 15 Orthogonal analysis table

[0247]

[0248] In order to optimize the best index, the K value in the intuitive analysis table is closer to the level of prescription-related data. From the intuitive analysis table, it can be seen that the best extraction process with baicalin extraction rate as the index is A2B2C2. From the variance analysis table, it can be seen that the C factor, that is, the number of extractions, is statistically significant (p<0.05), and the A and B factors are not statistically significant (P>0.05). From the orthogonal intuitive result table, the two extraction processes of A2B2C2 and A3B2C3 are optimized. In the experiment, since the A factor was not statistically significant, in order to be close to the clinical prescription usage, the A factor in the second extraction process was optimized to level 2. Next, the two selected extraction processes will be further compared and verified.

[0249] (5) Optimization of water extraction process

[0250] According to the prescription ratio, 6 portions of medicinal materials were weighed and the extraction process was optimized. The verification results are shown in Tables 16-17.

[0251] Table 16 Process optimization verification experiment (A2B2C3)

[0252] Serial number Baicalin extraction rate (%) Cream yield (%) Alcohol extract (%) 1 53.34 32.56 44.79 2 52.11 32.90 43.89 3 57.55 32.59 45.92 average value 54.33 32.68 44.87 Difference 14.39 6.14 -2

[0253] Table 17 Process optimization verification experiment (A2B2C2)

[0254] Serial number Baicalin extraction rate (%) Cream yield (%) Alcohol extract (%) 1 46.62 28.02 47.85 2 51.29 28.36 47.91 3 41.13 28.23 48.96 average value 46.34 28.20 48.24 Difference 6.4 1.66 -1.37

[0255] Through direct comparison of the data, it was found that the extraction rate of baicalin in the A2B2C2 process was closer to that in the prescription method; the paste yield and alcohol extract of the A2B2C2 process were closer to the liquid prepared by the prescription method. Based on the extraction of all the above index components, the paste yield and alcohol extract, A2B2C2 was selected, i.e., adding 6 times of water, extracting for 1 hour each time, and extracting twice as much as the optimal water extraction process.

[0256] (6) Water extraction process verification

[0257] Three portions of medicinal materials were weighed at 3 times the amount in the prescription, and extraction verification experiments were carried out according to the optimal process to examine the stability of the extraction method. The results are shown in Table 18.

[0258] Table 18 Water extraction process verification test verification

[0259]

[0260] The results show that this method has good repeatability, is stable and feasible. The prescription extraction method is determined to be to add six times the amount of water to soak the medicinal materials for half an hour, and then extract them twice with six times the amount of water, each time for one hour. This method will be used in subsequent experiments.

[0261] 2. Investigation of concentration and drying process

[0262] In order to investigate the effects of temperature and concentrated density on baicalin during the concentration and drying process, the concentration temperature, thick paste density and drying temperature of the water extract were optimized by single factor experiment with their transfer rate as the investigation index.

[0263] (1) Investigation of the concentration temperature and density of water extract

[0264] Weigh 3 times the amount of medicinal materials according to the prescription ratio, obtain water extract according to the optimal extraction process and dilute to 5000mL. Accurately measure 12 portions of water extract, 400mL each, and concentrate under reduced pressure at 60℃, 70℃, and 80℃ to thick pastes with relative densities of 1.05-1.10 (60℃), and under reduced pressure at 70℃ to thick pastes with relative densities of 1.00-1.05 (60℃) and 1.10-1.15 (60℃). Two portions of water extract for each condition, and the remaining two portions of water extract as blank controls, cool to room temperature, dilute with water and make up to 500mL, shake well, filter and test. Record the peak area of ​​baicalin, and calculate its retention rate according to formula (3). The results are shown in Tables 19-20.

[0265]

[0266] Table 19 Investigation of water extract concentration temperature (n=2)

[0267] Temperature(℃) Baicalin transfer rate (%) 60 98.95 70 97.94 80 97.94

[0268] Table 20 Density of concentrated thick paste of water extract (n=2)

[0269] <![CDATA[Density (g / cm 3 )]]> Baicalin transfer rate (%) 1.00-1.05(60℃) 97.55 1.05-1.10(60℃) 97.94 1.10-1.15(60℃) 97.32

[0270] The test results show that when baicalin and four alkaloids were concentrated under reduced pressure at 60℃, 70℃ and 80℃, the retention rate of baicalin was above 90% and the loss was small, indicating that the concentration temperature has little effect on the index components and the concentration temperature of the extract can be controlled below 80℃.

[0271] When the extract is concentrated under reduced pressure to a relative density of 1.00-1.05 (60°C), 1.05-1.10 (60°C), and 1.10-1.15 (60°C), the retention rate of baicalin is above 90%, with less loss. The relative density of the concentrated extract can be controlled at 1.00-1.15 (60°C).

[0272] (2) Drying temperature investigation

[0273] Weigh 2 portions of 3 times the amount of the medicinal material according to the prescription ratio, extract according to the preferred process, filter, combine the filtrate, and concentrate the water extract at 80°C under reduced pressure to a thick paste with a relative density of 1.00-1.15 (60°C). Weigh 8 portions of 30g of thick paste in a clean evaporating dish, 6 of which are dried under reduced pressure at 60°C, 70°C, and 80°C to obtain dry paste, and the other two portions of thick paste are used as blank controls. The dry paste and the thick paste are completely dissolved in water and the water is collected in a 500mL volumetric flask. After shaking, the baicalin content is detected. The transfer rate of baicalin dried at different temperatures is calculated according to formula (4). The results are shown in Table 21.

[0274]

[0275] Table 21 Thick paste drying temperature investigation (n=2)

[0276]

[0277]

[0278] The test results show that when the drying temperature is greater than 60°C, the baicalin retention rate is less than 90%, and the loss is large, so the drying temperature should not be greater than 60°C.

[0279] summary

[0280] The above test results show that the optimal preparation process is 6 times water, 2 extractions, 1 hour each time, soaking the medicinal materials for half an hour before extraction, and adding rhubarb and magnolia bark 10 minutes before the end of the first extraction. The concentration temperature is controlled at no more than 80°C, and the drying temperature is controlled at no more than 60°C.

[0281] 3. Molding process research

[0282] This prescription has long been used in clinical practice in the form of a decoction. In order to facilitate patients to carry and use it for a long time, this prescription is made into granules with a large drug loading capacity.

[0283] Instruments and reagents

[0284] (1) Medicinal materials and medicines

[0285] Extract powder (20220511, homemade); dextrin; soluble starch; lactose; ethanol (95%); Wahaha purified water

[0286] (2) Instruments

[0287] 0.01 mg electronic balance (MS105DU, Mettler-Toledo GmbH);

[0288] 0.01 g electronic balance (YP5002, Shanghai Youke Instrument Co., Ltd.);

[0289] Blast drying oven (DHG-9145A, Shanghai Yiheng Scientific Instrument Co., Ltd.);

[0290] High-speed universal pulverizer (FW-200, Beijing Kewei Yongxing Instrument Co., Ltd.)

[0291] Performance inspection of dry paste powder

[0292] (1) Determination of moisture absorption percentage of dry paste powder

[0293] The moisture absorption rate of dry paste powder and dry paste powder mixed with different excipients was investigated to provide a reference for the subsequent selection of excipients. Common excipients dextrin, soluble starch and lactose were selected for investigation. The powder was mixed evenly with dextrin, lactose and soluble starch in a ratio of 1:1 and set aside. Take an appropriate amount of the above materials and place them in a dry and clean weighing bottle. Immediately weigh the total weight of the weighing bottle and the materials accurately. Place it in a glass desiccator with a supersaturated NaCl solution (relative humidity of 75%) at the bottom without covering it. Place it indoors and weigh the total weight regularly. Calculate the moisture absorption percentage according to formula (5). The results are shown in Table 1.

[0294] Table 22, plotting the moisture absorption percentage curve Figure 7 .

[0295]

[0296] Table 22 Moisture absorption percentage

[0297]

[0298]

[0299] Results: The moisture absorption percentage of the dry paste powder reached 12% after 24 hours of placement, and exceeded 20% after 7 days of placement, indicating that the dry paste powder has strong hygroscopicity. After adding auxiliary materials, the moisture absorption percentage of the dry paste powder decreased, and the hygroscopicity was significantly improved. Among them, dextrin and soluble starch had similar effects on improving the hygroscopicity of the dry paste powder, and lactose was slightly better than these two auxiliary materials. These three auxiliary materials can be used as auxiliary materials to improve the hygroscopicity of the dry paste powder.

[0300] Wet granulation investigation

[0301] Take dry paste powder, use dextrin, soluble starch, lactose and other excipients, take granule properties and granule qualified rate as inspection indicators, inspect the drug-excipient ratio, excipient types and wetting agent, and select the best preparation molding process and parameters.

[0302] (1) Selection of wetting agent

[0303] Ethanol is commonly used as a wetting agent in wet granulation, so ethanol is selected as the wetting agent.

[0304] (2) Investigation of auxiliary materials

[0305] From the results of the hygroscopicity investigation, it can be seen that the three excipients, dextrin, soluble starch and lactose, can reduce the hygroscopicity of dry paste powder. Therefore, the granulation condition is used as the investigation index to further optimize the excipients. The drug-excipient ratio is fixed at 2:1, the wetting agent concentration is 95%, and the soft material properties, granulation difficulty, and molding rate are used as evaluation indicators. The results are shown in Table 23.

[0306] The evaluation criteria are as follows:

[0307] ① Soft material property standard: can be squeezed into a ball by hand and will fall apart when pressed lightly.

[0308] ② Difficulty of granulation: easy to sieve, less lumps, small lumps are easy to twist apart, auxiliary materials and extract powder are mixed evenly and not easy to separate.

[0309] ③ Calculation method of particle forming rate:

[0310]

[0311] Note: Qualified particles: particles that can pass through the No. 1 sieve but cannot pass through the No. 5 sieve.

[0312] Table 23 Investigation of auxiliary materials

[0313]

[0314] Both dextrin and lactose can be used as excipients for granulation. After adding soluble starch, there is more fine powder and it is not easy to form. When lactose is used as an excipient, the drug and the excipient are easy to separate and difficult to mix evenly, and the dextrin forming rate is higher, so dextrin is selected as the granulation excipient.

[0315] (3) Investigation of drug-excipient ratio and wetting agent

[0316] The experiment was carried out according to the conventional drug-excipient ratio of 2:1, 3:2, and 1:1. Appropriate amounts of dry paste powder and dextrin were evenly mixed in the ratio of 2:1, 3:2, and 1:1, respectively, and granulated using 95% and 90% ethanol concentrations, respectively. The results are shown in Table 24.

[0317] Table 24 Granule molding process optimization test results

[0318]

[0319]

[0320] When the wetting agent concentration is 95%, the molding rate is high. When the wetting agent concentration is reduced to 90% or below, granulation is difficult and the molding rate is low. Therefore, 95% ethanol is selected as the wetting agent. The molding rates of the three drug-excipient ratios are not much different. In order to minimize the dosage, 2:1 is selected as the drug-excipient ratio. According to the results of the previous tests, the daily prescription amount of medicinal materials can obtain about 28g of dry paste. Granulation with a drug-excipient ratio of 2:1 can use 42g of granules per day, and each 1g is equivalent to 2.36g of decoction pieces.

[0321] Process test inspection

[0322] Take 3 times the daily prescription amount of medicinal materials, each about 297g, extract using the optimal process, concentrate under reduced pressure at 80℃, vacuum dry at 60℃, take the daily prescription amount of dry paste powder and add dextrin to 42g, and granulate with 95% ethanol. Add appropriate amount of granules to appropriate amount of water to dissolve, and determine the content of baicalin and four alkaloids. Investigate the process stability, the results are shown in Table 25.

[0323] Table 25 Small test results

[0324]

[0325] Results: There was no significant difference in the baicalin content among the daily prescriptions, and the above extraction, concentration, drying and molding processes were stable and feasible.

[0326] The above are only preferred embodiments of the present application. It should be noted that the above preferred embodiments should not be regarded as limiting the present application, and the protection scope of the present application should be based on the scope defined by the claims. For ordinary technicians in this technical field, several improvements and modifications can be made without departing from the spirit and scope of the present application, and these improvements and modifications should also be regarded as the protection scope of the present application.

Claims

1. A Chinese medicine composition for treating functional dyspepsia, characterized in that: The Chinese medicine composition is prepared from the following Chinese medicine raw materials in parts by weight: 7-11 parts of ginger pinellia, 7-11 parts of wine scutellaria, 3-7 parts of wine coptis, 7-11 parts of dried ginger, 7-11 parts of codonopsis pilosula, 4-8 parts of amomum, 2-4 parts of raw rhubarb, 7-11 parts of turmeric, 7-11 parts of magnolia bark, 7-11 parts of stir-fried white peony root, 8-12 parts of vinegar corydalis, 4-8 parts of roasted licorice, and 4-8 parts of jujube.

2. The Chinese medicine composition for treating functional dyspepsia according to claim 1, characterized in that: The Chinese medicine composition is prepared from the following Chinese medicine raw materials in parts by weight: 9 parts of ginger pinellia, 9 parts of wine scutellaria, 5 parts of wine coptis, 9 parts of dried ginger, 9 parts of codonopsis, 6 parts of amomum, 3 parts of raw rhubarb, 9 parts of curcuma, 9 parts of magnolia bark, 9 parts of stir-fried white peony root, 10 parts of vinegar corydalis, 6 parts of roasted liquorice, and 6 parts of jujube.

3. A Chinese medicine preparation for treating functional dyspepsia, characterized in that: The traditional Chinese medicine preparation is composed of traditional Chinese medicine ingredients and pharmaceutically acceptable excipients, and the traditional Chinese medicine ingredients are prepared from the traditional Chinese medicine composition described in any one of claims 1-2.

4. The Chinese medicine preparation according to claim 3, characterized in that: The traditional Chinese medicine preparation is a granule, and the excipient of the granule is one or more of lactose, dextrin or soluble starch.

5. The Chinese medicine preparation according to claim 4, characterized in that: The excipient is dextrin, and the drug-excipient ratio of the traditional Chinese medicine component to the excipient is 1:1-3:

1.

6. A method for preparing the Chinese medicine preparation for treating functional dyspepsia as claimed in claim 5, characterized in that: The method comprises the following steps: The Chinese medicine raw materials are weighed according to weight ratio, extracted, filtered, the filtrates are combined, concentrated, and auxiliary materials are added to prepare Chinese medicine preparations.

7. The preparation method according to claim 6, characterized in that: The method comprises the following steps: The Chinese medicine raw materials are weighed according to the weight ratio, decocted with water for extraction, filtered, the filtrates are combined, and concentrated under reduced pressure to obtain a thick paste, the thick paste is dried to obtain a dry paste, and auxiliary materials are added to prepare a Chinese medicine preparation; wherein the water decoction is 5-10 times of water, and the extraction is performed 2-4 times, each time for 0.5-2 hours, the medicinal materials are soaked for 0.5-4 hours before extraction, and rhubarb and magnolia bark are added 5-20 minutes before the end of the first extraction; the concentration temperature is controlled at no more than 90°C, and the drying temperature is controlled at no more than 80°C.

8. Use of the traditional Chinese medicine composition according to claim 1 in preparing a drug for treating functional dyspepsia.

9. Use of the Chinese medicine composition according to claim 1 in the preparation of a medicament for treating psychiatric symptoms associated with functional dyspepsia, wherein the psychiatric symptoms are anxiety or depression associated with functional dyspepsia.

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