Use of baoji oral liquid composition in the preparation of functional dyspepsia drugs

Abstract

The application provides application of a Baoji oral liquid composition in preparation of a functional dyspepsia medicine, and relates to the technical field of medicines. The application is based on the Baoji oral liquid, and it is found that the Baoji oral liquid has a remarkable effect on treating functional dyspepsia, especially cisplatin-induced functional dyspepsia. Specifically, the Baoji oral liquid can rapidly restore body weight, significantly improve body weight gain, steadily promote food intake, significantly improve gastric emptying rate and intestinal propulsion rate, protect the gastric mucosa layer, reduce inflammatory cell infiltration, repair the mucosa layer and muscle layer, improve the expression of serum gastrin and motilin, and improve the expression level of IL-4 in the gastric tissue and reduce the expression level of IL-1beta. The Baoji oral liquid has remarkable efficacy when applied in preparation of a functional dyspepsia medicine.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the application of Baoji oral liquid composition in the preparation of functional dyspepsia drugs. Background Technology

[0002] Functional dyspepsia (FD) is a specific type of disease with main symptoms such as upper abdominal pain, upper abdominal distension, early satiety, belching, loss of appetite, nausea, and vomiting. It is a group of clinical syndromes after ruling out organic diseases and is one of the common functional gastrointestinal disorders in clinical practice.

[0003] Functional dyspepsia is significantly different from "indigestion," and the main distinctions are as follows:

[0004] 1. Different definitions:

[0005] Indigestion: refers to a group of clinical syndromes characterized by symptoms such as upper abdominal pain, burning sensation, postprandial fullness, and early satiety, which can be caused by a variety of reasons. Functional dyspepsia: is a group of clinical syndromes characterized by upper abdominal pain, upper abdominal distension, early satiety, belching, loss of appetite, nausea, and vomiting, after ruling out organic diseases. It is one of the most common functional gastrointestinal disorders in clinical practice.

[0006] 2. Different causes:

[0007] Etiology of indigestion: (1) Organic causes: including gastrointestinal diseases (peptic ulcer, chronic gastritis, gastroesophageal reflux disease, gastrointestinal tumors), hepatobiliary and pancreatic diseases (hepatitis, cholecystitis, pancreatitis), and systemic diseases (diabetes, hypothyroidism). (2) Functional causes: gastrointestinal motility disorders, visceral hypersensitivity, and psychological factors, but not meeting the diagnostic criteria for functional dyspepsia.

[0008] Etiology of functional dyspepsia: The pathogenesis is not yet fully understood. Studies have shown that it is related to gastrointestinal motility disorders, such as delayed gastric emptying and abnormal gastroduodenal coordination; visceral hypersensitivity; psychological factors, such as anxiety, depression, and stress; Helicobacter pylori infection; and genetic factors.

[0009] 3. Different diagnostic criteria:

[0010] Diagnosis of dyspepsia requires examination of medical history, physical examination, laboratory tests, and imaging studies (such as gastroscopy and abdominal ultrasound) to determine the presence of organic lesions. In Western medicine, the diagnostic criteria for functional dyspepsia include: persistent or recurrent upper abdominal pain, burning sensation in the upper abdomen, postprandial bloating, early satiety, belching, nausea, vomiting, and acid reflux; symptoms are not relieved after defecation or are unrelated to changes in defecation frequency or stool consistency; and the symptoms cannot be explained by other diseases upon evaluation. In Traditional Chinese Medicine (TCM), the diagnostic criteria for functional dyspepsia manifest in the following patterns: food stagnation, spleen deficiency with food stagnation, damp-heat in the spleen and stomach, disharmony between the liver and stomach, mixed cold and heat patterns, and spleen and stomach deficiency with cold.

[0011] Currently, the drugs and methods for treating functional dyspepsia (FD) can be broadly categorized into acid-suppressing and antacids, prokinetic drugs, cyproheptadine, psychological intervention, traditional Chinese medicine (TCM) treatment, and probiotics. FD is prone to relapse, primarily affects young children, is difficult to cure, and long-term use of Western medicine can easily lead to drug resistance and significant side effects. Therefore, TCM treatment has shown unique advantages. The Clinical Application Guidelines for the Treatment of Functional Dyspepsia with Traditional Chinese Medicine (2021) indicate that four TCM preparations (Zhishu Kuanzhong Capsules, Qizhi Weitong Granules, Biling Weitong Granules, and Jinghua Weikang Capsules) have strong evidence supporting their effectiveness in treating FD. However, because the pathological mechanism of functional dyspepsia is unclear, and different drugs have varying therapeutic effects on functional dyspepsia with different pathogenesis mechanisms, further in-depth research is needed on drugs treating functional dyspepsia with different pathogenesis mechanisms.

[0012] In addition, Chinese invention patent CN117357616A discloses a traditional Chinese medicine composition for pediatric functional dyspepsia, its preparation method, and its application. By weight, the composition comprises: 8-54 parts of Dioscorea opposita, 5-36 parts of Poria cocos, 5-36 parts of Citrus reticulata peel, 5-36 parts of Atractylodes macrocephala, 5-36 parts of Crataegus pinnatifida (roasted), 5-36 parts of Radish seed (roasted), 5-36 parts of Malt (roasted), and 4-18 parts of Glycyrrhiza uralensis. This composition has therapeutic effects on functional dyspepsia induced by rhubarb-induced spleen deficiency, functional dyspepsia in mice induced by irregular eating habits combined with L-arginine, and functional dyspepsia in rats induced by iodoacetamide combined with the small platform standing test. It can be used to treat functional dyspepsia in children caused by spleen and stomach weakness.

[0013] Chinese invention patent CN102240369A discloses a traditional Chinese medicine preparation for treating functional dyspepsia. It selects Chinese herbs with the functions of strengthening the spleen and consolidating the foundation, nourishing the earth and replenishing qi, and harmonizing the stomach and promoting downward flow: red peony root, white atractylodes rhizome, cimicifuga rhizome, stir-fried germinated barley, poria cocos, astragalus root, cinnamon twig, chrysanthemum, fennel, costus root, immature bitter orange, areca nut, magnolia bark, angelica root, and radish seed to decoct into a soup for patients to take.

[0014] Baoji Oral Liquid is composed of 16 medicinal herbs, including Uncaria rhynchophylla. Its effects include relieving exterior syndromes, dispelling dampness, and harmonizing the stomach. It is used to treat abdominal pain, vomiting, diarrhea, indigestion, acid reflux, nausea, vomiting, gastrointestinal discomfort, indigestion, motion sickness, seasonal colds, fever, and headache. Although there are many existing studies on traditional Chinese medicine preparations for treating functional dyspepsia, there is currently no research or application regarding the use of Baoji Oral Liquid in the preparation of drugs for treating cisplatin-induced functional dyspepsia. Summary of the Invention

[0015] This invention addresses the problems existing in the prior art by providing the application of Baoji oral liquid composition in the preparation of drugs for functional dyspepsia. Based on the components and preparation method of Baoji oral liquid, the obtained Baoji oral liquid has a significant therapeutic effect on functional dyspepsia, especially cisplatin-induced functional dyspepsia, providing a new approach for the selection of drugs for the treatment of functional dyspepsia.

[0016] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0017] On the one hand, the present invention provides the use of the Baoji oral liquid composition in the preparation of a medicament for treating functional dyspepsia.

[0018] Preferably, the treatment of functional dyspepsia includes rapid weight recovery and significant improvement in weight gain.

[0019] Preferably, the treatment of functional dyspepsia includes promoting a steady recovery of food intake.

[0020] Preferably, the treatment of functional dyspepsia includes significantly increasing gastric emptying rate.

[0021] Preferably, the treatment of functional dyspepsia includes significantly increasing intestinal propulsion rate.

[0022] Preferably, the treatment of functional dyspepsia includes protecting the gastric mucosa, reducing inflammatory cell infiltration, and repairing the mucosal layer.

[0023] Preferably, the treatment of functional dyspepsia includes significantly increasing the expression of gastrin and motilin in serum.

[0024] Preferably, the treatment of functional dyspepsia includes significantly increasing the expression levels of IL-4 and decreasing the expression levels of IL-1β in gastric tissue.

[0025] More preferably, the treatment of functional dyspepsia is treatment of cisplatin-induced functional dyspepsia.

[0026] Preferably, in the application, the drug comprises components of the Baoji oral liquid composition, or may be administered in combination with one or more other therapeutic agents.

[0027] More preferably, in the application, the drug may also be administered in combination with a pharmaceutically acceptable carrier.

[0028] In this invention, the pharmaceutically acceptable carrier refers to all pharmaceutically acceptable carriers, including but not limited to diluents, binders, absorbents, disintegrants, dispersants, humectants, solubilizers, buffers, and surfactants.

[0029] In this invention, the type and manufacturer of the pharmaceutically acceptable carrier do not significantly affect the technical efficacy of the drug.

[0030] In this invention, the pharmaceutically acceptable carrier may be starch, dextrin, sucrose, milk powder, sweetener, mannitol, lactose, cellulose and its derivatives, calcium carbonate, cyclodextrin, β-cyclodextrin, phospholipids, magnesium stearate, talc, or flavoring.

[0031] Preferably, in the application, the drug is administered via oral, sublingual, oral mucosal, intravenous, intramuscular, intraperitoneal, subcutaneous, transdermal, nasal, and rectal routes.

[0032] In this invention, the dosage form of the drug can be solid, liquid, or gas.

[0033] Preferably, in the application, the dosage form of the drug includes powder, tablet, granule, pill, hard capsule or soft capsule, cream, ointment, plaster, gel, paste, powder, patch, solution, suspension, injection, syrup, liniment, emulsion, tincture, elixir, aerosol and spray.

[0034] On the other hand, the present invention provides a medicine for treating functional dyspepsia, the components of which include the components of the Baoji oral liquid composition; the components of the Baoji oral liquid composition include: Uncaria rhynchophylla, Mentha haplocalyx, Tribulus terrestris, Angelica dahurica, Aucklandia lappa, Guangdong Shenqu (medicated leaven), Chrysanthemum morifolium, Pogostemon cablin, Atractylodes lancea, Poria cocos, Magnolia officinalis, Citrus reticulata peel, Trichosanthes kirilowii, Coix lacryma-jobi, Pueraria lobata, and Oryza sativa sprout.

[0035] Preferably, the dosage of the Baoji oral liquid composition in the drug is 365 mg crude drug / kg / d to 1460 mg crude drug / kg / d.

[0036] More preferably, the dosage of the Baoji oral liquid composition in the drug is 730 mg crude drug / kg / d to 1460 mg crude drug / kg / d.

[0037] In this invention, the raw materials of the Baoji oral liquid composition include: Uncaria rhynchophylla, Mentha haplocalyx, Tribulus terrestris, Angelica dahurica, Aucklandia lappa, Guangdong Shenqu (a type of fermented medicinal herb), Chrysanthemum morifolium, Pogostemon cablin, Atractylodes lancea, Poria cocos, Magnolia officinalis, Citrus reticulata peel, Trichosanthes kirilowii, Coix lacryma-jobi, Pueraria lobata, and rice sprouts.

[0038] Alternatively, the Baoji oral liquid composition may be a product prepared according to the components, proportions, and preparation methods described in prior patent CN100998782A, or a product prepared according to the components, proportions, and preparation methods described in the 2020 edition of the Chinese Pharmacopoeia.

[0039] Preferably, the raw materials of the Baoji oral liquid composition, by weight, include the following components: 2.5-4.5 parts Uncaria rhynchophylla, 4-8 parts Mentha haplocalyx, 2.5-4.5 parts Tribulus terrestris, 10-16 parts Angelica dahurica, 10-16 parts Aucklandia lappa, 10-16 parts Guangdong Shenqu (medicated leaven), 5-8 parts Chrysanthemum morifolium, 10-16 parts Pogostemon cablin, 10-16 parts Atractylodes lancea, 22-36.8 parts Poria cocos, 10-16 parts Magnolia officinalis, 5-8 parts Citrus reticulata peel, 7-14 parts Trichosanthes kirilowii, 14-20.2 parts Coix lacryma-jobi, 10-16 parts Pueraria lobata, and 8-12 parts Oryza sativa sprouts.

[0040] In this embodiment of the invention, the Baoji oral liquid composition used is Baoji oral liquid extract. Its raw medicinal materials, by weight, are: 3.4 parts Uncaria rhynchophylla, 6.8 parts Mentha haplocalyx, 3.4 parts Tribulus terrestris, 13.6 parts Angelica dahurica, 13.6 parts Aucklandia lappa, 13.6 parts Guangdong Shenqu (medicated leaven), 6.8 parts Chrysanthemum morifolium, 13.6 parts Pogostemon cablin, 13.6 parts Atractylodes lancea, 27.3 parts Poria cocos, 13.6 parts Magnolia officinalis, 6.8 parts Citrus reticulata peel, 10.2 parts Trichosanthes kirilowii, 17.1 parts Coix lacryma-jobi, 13.6 parts Pueraria lobata, and 10.2 parts Oryza sativa sprouts;

[0041] The preparation method is as follows: The above sixteen herbs, including Aucklandia lappa, Atractylodes lancea, Mentha haplocalyx, Pogostemon cablin, and Citrus reticulata, are steam distilled for 2 hours, and the volatile oil is collected and stored separately. The dregs and the aqueous solution after oil extraction are decocted twice with water, 1.5 hours each time. The decoctions are filtered, the filtrates are combined, and concentrated to a relative density of 1.08-1.12 (60℃). After cooling, ethanol is added to make the alcohol content reach 45% (volume concentration). The mixture is allowed to stand overnight, filtered, the ethanol is recovered, and concentrated into extract one for later use. The herbs, including Uncaria rhynchophylla, Tribulus terrestris, Chrysanthemum morifolium, Magnolia officinalis, and Guangdong Shenqu, are decocted twice with water, the first time for 2 hours and the second time for 1.5 hours. The decoctions are combined, filtered, and the filtrates are concentrated to a relative density of 1.02-1.05 (60℃). After cooling, ethanol is added to make the alcohol content reach 40% (volume concentration). (Volume concentration), let stand overnight, filter, recover ethanol and concentrate to extract two, for later use; take coix seed and rice sprout, decoct twice with water, one hour each time, combine the decoctions, filter, concentrate the filtrate to a relative density of 1.02-1.05 (60℃), cool, add ethanol to make the alcohol content 45% (volume concentration), let stand overnight, filter, recover ethanol and concentrate to extract three, for later use; take poria cocos, trichosanthes root, angelica dahurica and kudzu root, decoct twice with water, the first time for 2 hours, the second time for 1 hour, combine the decoctions, filter, concentrate the filtrate to a relative density of 1.02-1.05 (60℃), cool, add ethanol to make the alcohol content 60% (volume concentration), let stand overnight, filter, recover ethanol and concentrate to extract four, for later use. All the above extracts are stirred evenly, sterilized, and the Baoji oral liquid composition (extract) is obtained.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] 1. The Baoji oral liquid composition of the present invention is used in the preparation of a drug for treating functional dyspepsia. It can rapidly restore the weight of mice with functional dyspepsia induced by cisplatin injection, and significantly improve weight gain; it can significantly improve gastric emptying rate and intestinal propulsion rate, protect the gastric antral mucosa, reduce inflammatory cell infiltration, and repair the mucosa.

[0044] 2. The Baoji oral liquid composition of the present invention has a significant therapeutic effect on functional dyspepsia compared with other similar formulations; it can significantly promote the rapid recovery of body weight and rapid restoration of food intake in mice with functional dyspepsia induced by cisplatin; and it can significantly improve the gastric emptying rate and intestinal propulsion rate in mice with functional dyspepsia induced by cisplatin.

[0045] 3. The Baoji oral liquid composition of the present invention can significantly increase the expression of gastrin and motilin in the serum of mice with functional dyspepsia; it can significantly increase the expression level of IL-4 in the gastric tissue of mice with functional dyspepsia and decrease the expression level of IL-1β. Attached Figure Description

[0046] Figure 1This is an animal experiment flowchart for a cisplatin-induced functional dyspepsia model in mice.

[0047] Figure 2 This is a comparison chart of weight changes in different groups of mice in a cisplatin-induced functional dyspepsia model.

[0048] Figure 3 This is a comparison chart of the changes in average daily food intake among different groups of mice in a cisplatin-induced functional dyspepsia mouse model.

[0049] Figure 4 This is a comparison of gastric emptying rates among different groups of mice in a cisplatin-induced functional dyspepsia model.

[0050] Figure 5 This is a comparative chart of intestinal propulsion rates in different groups of mice in a cisplatin-induced functional dyspepsia model.

[0051] Figure 6 This is a comparison of HE staining of sinus tissue in mice from different groups of a cisplatin-induced functional dyspepsia model, magnified 100 times.

[0052] Figure 7 This is a comparison chart of serum gastrin levels in different groups of mice in a cisplatin-induced functional dyspepsia model.

[0053] Figure 8 This is a comparison chart of serum motilin levels in different groups of mice in a cisplatin-induced functional dyspepsia model.

[0054] Figure 9 This is a comparison of interleukin-4 levels in the gastric tissue of mice in different groups of a cisplatin-induced functional dyspepsia model.

[0055] Figure 10 This is a comparison of interleukin-1β levels in the gastric tissue of mice in different groups of a cisplatin-induced functional dyspepsia model.

[0056] Figure 11 This is a comparison of gastric emptying rates among different groups of mice in a loperamide-induced functional dyspepsia mouse model.

[0057] Figure 12 This is a comparative chart of intestinal propulsion rates in different groups of mice in a loperamide-induced functional dyspepsia mouse model.

[0058] Figure 13 This is a comparison of serum gastrin levels in different groups of mice in a loperamide-induced functional dyspepsia model.

[0059] Figure 14 This is a comparison of serum motilin levels in different groups of mice in a loperamide-induced functional dyspepsia model.

[0060] Figure 15 This is a comparison of interleukin-4 levels in the gastric tissue of mice in different groups of a loperamide-induced functional dyspepsia model.

[0061] Figure 16 This is a comparison of interleukin-1β levels in gastric tissue of mice in different groups of a loperamide-induced functional dyspepsia model. Detailed Implementation

[0062] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0063] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0064] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all chemical reagents used in the embodiments of the present invention are obtained through conventional commercial channels. Products from different manufacturers do not have a significant impact on the effectiveness.

[0065] In the following examples, “part” and “g” have the same meaning, that is, 1 part = 1g.

[0066] Basic Implementation

[0067] The Baoji oral liquid composition is prepared from the following raw medicinal materials: 2.5-4.5 parts Uncaria rhynchophylla, 4-8 parts Mentha haplocalyx, 2.5-4.5 parts Tribulus terrestris, 10-16 parts Angelica dahurica, 10-16 parts Aucklandia lappa, 10-16 parts Guangdong Shenqu (medicated leaven), 5-8 parts Chrysanthemum morifolium, 10-16 parts Pogostemon cablin, 10-16 parts Atractylodes lancea, 22-36.8 parts Poria cocos, 10-16 parts Magnolia officinalis, 5-8 parts Citrus reticulata peel, 7-14 parts Trichosanthes kirilowii, 14-20.2 parts Coix lacryma-jobi, 10-16 parts Pueraria lobata, and 8-12 parts Oryza sativa sprouts.

[0068] The preparation method of Baoji Oral Liquid Extract (Baoji Oral Liquid Composition) is as follows:

[0069] Take the above-mentioned five medicinal materials: costus root, atractylodes rhizome, peppermint, patchouli, and tangerine peel, combine them, soak them in 0.5-2 times the amount of water for 0.5-2 hours, then steam distill for 1-3 hours, collect the volatile oil and store it separately; decoct the dregs with water 1-3 times, each time for 1-2 hours, combine the decoctions, filter, concentrate the filtrate to a relative density of 1.04-1.20 at 45℃-75℃, cool, add ethanol to make the alcohol content reach 40%-55% (volume concentration), let stand for 4-36 hours, filter, recover the ethanol; concentrate to a relative density of 1.25-1.45 at 45℃-75℃ to obtain extract one, for use;

[0070] Take the above-mentioned five medicinal materials: Uncaria rhynchophylla, Tribulus terrestris, Chrysanthemum morifolium, Magnolia officinalis, and Guangdong Shenqu (medicated leaven). Combine them, add water and decoct 1-3 times, each time for 1-3 hours. Combine the decoctions, filter, and concentrate the filtrate to a relative density of 1.02-1.05 at 45℃-75℃. Cool, add ethanol to make the alcohol content reach 30%-50% (volume concentration), let stand for 4-36 hours, filter, and recover the ethanol. Concentrate to a relative density of 1.05-1.10 at 45℃-75℃ to obtain extract II, for later use.

[0071] Take the above-mentioned coix seed and rice sprout, combine them, add water and decoct 1-3 times, each time for 0.5-2 hours, combine the decoctions, filter, concentrate the filtrate to a relative density of 1.02-1.05 at 45℃-75℃, cool, add ethanol to make the alcohol content reach 35%-55% (volume concentration), let stand for 4-36 hours, filter, recover the ethanol; concentrate to a relative density of 1.05-1.10 at 45℃-75℃ to obtain extract 3, for use;

[0072] Take the above-mentioned four medicinal materials, Poria cocos, Trichosanthes kirilowii, Angelica dahurica, and Pueraria lobata, and decoct them 1-3 times with water, each time for 0.5-3 hours. Combine the decoctions, filter, and concentrate the filtrate to a relative density of 1.01-1.15 at 45℃-75℃. Cool, add ethanol to make the alcohol content reach 50%-70% (volume concentration), let stand for 4-36 hours, filter, and recover the ethanol; concentrate to a relative density of 1.02-1.20 at 45℃-75℃ to obtain extract IV, for later use.

[0073] The above extracts were mixed evenly and sterilized to obtain Baoji Oral Liquid Extract.

[0074] All technical solutions within the scope of the above-described basic embodiments can achieve the technical effects described in this invention, and achieve a significant therapeutic effect on cisplatin-induced functional dyspepsia in mice.

[0075] Example 1

[0076] The raw materials of Baoji Oral Liquid Extract, by weight, are: 3.4 parts Uncaria rhynchophylla, 6.8 parts Mentha haplocalyx, 3.4 parts Tribulus terrestris, 13.6 parts Angelica dahurica, 13.6 parts Aucklandia lappa, 13.6 parts Guangdong Shenqu (medicated leaven), 6.8 parts Chrysanthemum morifolium, 13.6 parts Pogostemon cablin, 13.6 parts Atractylodes lancea, 27.3 parts Poria cocos, 13.6 parts Magnolia officinalis, 6.8 parts Citrus reticulata peel, 10.2 parts Trichosanthes kirilowii, 17.1 parts Coix lacryma-jobi, 13.6 parts Pueraria lobata, and 10.2 parts Oryza sativa sprouts;

[0077] The preparation method is as follows: The above sixteen herbs, including Aucklandia lappa, Atractylodes lancea, Mentha haplocalyx, Pogostemon cablin, and Citrus reticulata, are steam distilled for 2 hours, and the volatile oil is collected and stored separately. The dregs and the aqueous solution after oil extraction are decocted twice with water, 1.5 hours each time. The decoctions are filtered, the filtrates are combined, and concentrated to a relative density of 1.08-1.12 (60℃). After cooling, ethanol is added to make the alcohol content reach 45% (volume concentration). The mixture is allowed to stand overnight, filtered, the ethanol is recovered, and concentrated into extract one for later use. The herbs, including Uncaria rhynchophylla, Tribulus terrestris, Chrysanthemum morifolium, Magnolia officinalis, and Guangdong Shenqu, are decocted twice with water, the first time for 2 hours and the second time for 1.5 hours. The decoctions are combined, filtered, and the filtrates are concentrated to a relative density of 1.02-1.05 (60℃). After cooling, ethanol is added to make the alcohol content reach 40% (volume concentration). (Volume concentration), let stand overnight, filter, recover ethanol and concentrate to extract two, for later use; take coix seed and rice sprout, decoct twice with water, one hour each time, combine the decoctions, filter, concentrate the filtrate to a relative density of 1.02-1.05 (60℃), cool, add ethanol to make the alcohol content 45% (volume concentration), let stand overnight, filter, recover ethanol and concentrate to extract three, for later use; take poria cocos, trichosanthes root, angelica dahurica and kudzu root, decoct twice with water, the first time for 2 hours, the second time for 1 hour, combine the decoctions, filter, concentrate the filtrate to a relative density of 1.02-1.05 (60℃), cool, add ethanol to make the alcohol content 60% (volume concentration), let stand overnight, filter, recover ethanol and concentrate to extract four, for later use. All the above extracts are stirred evenly, sterilized, and the Baoji oral liquid composition (extract) is obtained.

[0078] Example 2

[0079] Baoji Oral Liquid Extract contains the following raw materials by weight: 2.5 parts Uncaria rhynchophylla, 4 parts Mentha haplocalyx, 2.5 parts Tribulus terrestris, 10 parts Angelica dahurica, 10 parts Aucklandia lappa, 10 parts Guangdong Shenqu (medicated leaven), 5 parts Chrysanthemum morifolium, 10 parts Pogostemon cablin, 10 parts Atractylodes lancea, 22 parts Poria cocos, 10 parts Magnolia officinalis, 5 parts Citrus reticulata peel, 7 parts Trichosanthes kirilowii, 14 parts Coix lacryma-jobi, 10 parts Pueraria lobata, and 8 parts Oryza sativa sprouts.

[0080] The preparation method of the above-mentioned Baoji oral liquid extract is the same as that in Example 1.

[0081] Example 3

[0082] Baoji Oral Liquid Extract contains the following raw materials by weight: 4.5 parts Uncaria rhynchophylla, 8 parts Mentha haplocalyx, 4.5 parts Tribulus terrestris, 16 parts Angelica dahurica, 16 parts Aucklandia lappa, 16 parts Guangdong Shenqu (medicated leaven), 8 parts Chrysanthemum morifolium, 16 parts Pogostemon cablin, 16 parts Atractylodes lancea, 36.8 parts Poria cocos, 16 parts Magnolia officinalis, 8 parts Citrus reticulata peel, 14 parts Trichosanthes kirilowii, 20.2 parts Coix lacryma-jobi, 16 parts Pueraria lobata, and 12 parts Oryza sativa sprouts.

[0083] The preparation method of the above-mentioned Baoji oral liquid extract is the same as that in Example 1.

[0084] Comparative Example 1

[0085] The Western medicine, Mosapride Citrate Tablets, is manufactured by Yabao Pharmaceutical Group Co., Ltd., and its batch number is National Drug Approval Number H20090158.

[0086] Comparative Example 2

[0087] The traditional Chinese medicine Huoxiang Zhengqi Capsules are manufactured by Tianjin Darentang Group Co., Ltd., and the batch number is National Medicine Approval Number Z10890019.

[0088] Comparative Example 3

[0089] The components of the traditional Chinese medicine composition, by weight, are: Uncaria rhynchophylla, Mentha haplocalyx, Tribulus terrestris, Aucklandia lappa, Chrysanthemum morifolium, Poria cocos, Magnolia officinalis, and Oryza sativa sprouts.

[0090] In the traditional Chinese medicine composition, the raw materials of the raw materials, by weight, are: 3.4 parts Uncaria rhynchophylla, 6.8 parts Mentha haplocalyx, 3.4 parts Tribulus terrestris, 13.6 parts Aucklandia lappa, 6.8 parts Chrysanthemum morifolium, 27.3 parts Poria cocos, 13.6 parts Magnolia officinalis, and 10.2 parts Oryza sativa sprouts.

[0091] The preparation method of the drug is the same as that of the extract in Example 1.

[0092] Comparative Example 4

[0093] The components of the traditional Chinese medicine composition, by weight, are: Angelica dahurica, Guangdong Shenqu (medicated leaven), Chrysanthemum, Patchouli, Atractylodes lancea, Citrus reticulata peel, Trichosanthes kirilowii, Coix lacryma-jobi, and Pueraria lobata.

[0094] In the traditional Chinese medicine composition, the raw materials of the raw materials, by weight, are: 13.6 parts Angelica dahurica, 13.6 parts Guangdong Shenqu (a type of fermented wheat), 6.8 parts Chrysanthemum, 13.6 parts Pogostemon cablin, 13.6 parts Atractylodes lancea, 6.8 parts Citrus reticulata peel, 10.2 parts Trichosanthes kirilowii, 17.1 parts Coix lacryma-jobi, and 13.6 parts Pueraria lobata.

[0095] The preparation method of the drug is the same as that of the extract in Example 1.

[0096] Experiment 1: Cisplatin-induced functional dyspepsia in mice

[0097] A cisplatin-induced functional dyspepsia model in mice was used. Different concentrations of the extract of Baoji Koufuye, the positive control drugs mosapride and Huoxiang Zhengqi Capsule were administered by gavage, and the changes in body weight and food intake of mice were observed. The gastric emptying rate, intestinal propulsion rate, and the expression levels of serum and tissue biochemical indexes in mice were measured to investigate the effect of the Baoji Koufuye composition on the functional dyspepsia model in young mice.

[0098] Figure 1 It is the flow chart of the animal experiment for the cisplatin-induced functional dyspepsia model in mice.

[0099] 1. Experimental materials

[0100] 1.1 Experimental animals

[0101]

[0102] 1.2 Experimental reagents

[0103] The main experimental reagents for the pharmacological effects of the functional dyspepsia model in mice are shown in Table 1.

[0104] Table 1 Main experimental reagents for the pharmacological effects of the functional dyspepsia model in mice

[0105]

[0106]

[0107] 1.3 Experimental instruments

[0108] The main experimental instruments for the pharmacological effects of the functional dyspepsia model in mice are shown in Table 2.

[0109] Table 2 Main experimental instruments for the pharmacological effects of the functional dyspepsia model in mice

[0110]

[0111] 2. Experimental methods

[0112] 2.1 Preparation of drug solutions

[0113] ​The cisplatin dose is 2 mg / kg. Accurately weigh 2 mg, add 1 mL of normal saline to prepare a 2 mg / mL stock solution, and then dilute with normal saline to 0.2 mg / mL. Administer a single dose of 0.1 mL / 10 g by gavage.

[0114] The dosage of mosapride citrate tablets is 20 mg / kg. Accurately weigh 20 mg of mosapride, add 1 mL of physiological saline to prepare a 20 mg / mL stock solution, and then dilute with physiological saline to 2 mg / mL. Administer a single dose of 0.1 mL / 10 g by gavage.

[0115] The specification of Huoxiang Zhengqi Capsules is 0.45g per capsule. The dosage is oral, 2-4 capsules each time, 1-2 times daily. Based on modern pharmacological research and routine clinical dosage, the clinical dosage of Huoxiang Zhengqi Capsules is 0.45g × 3 capsules × 1.5 times / 70kg = 0.029g / kg. The dosage used in this experiment is based on the commonly used clinical dosage, converted according to the body surface area conversion factor for humans and mice, i.e., 0.029g / kg × 9.1 = 0.264g / kg. Accurately weigh 0.45g of the contents of Huoxiang Zhengqi Capsules and add...

[0116] Prepare a stock solution of 264 mg / mL using 1.7 mL of physiological saline, then dilute it with physiological saline to 26.4 mg / mL. Administer the solution via gavage at a dose of 0.1 mL / 10 g.

[0117] The specification of Baoji oral liquid extract is that each 1mL is equivalent to 0.187g of medicinal slices. The dosage is 10mL orally, three times a day. According to modern pharmacological research and routine clinical dosage, the clinical dosage of Baoji oral liquid extract is 0.187g / mL × 10mL × 3 times / 70kg = 0.08g / kg. Converted using the body surface area conversion factor for humans and mice, this is 0.08g / kg × 9.1 = 0.728g / kg / day. To explore the optimal dosage of Baoji oral liquid extract in treating a mouse model of functional dyspepsia and to observe whether its pharmacological effects are dose-dependent, this experiment used the clinically equivalent dose of Baoji oral liquid extract as a reference and set up a low-dose group (0.365g crude drug / kg / day), a medium-dose group (0.73g crude drug / kg / day), and a high-dose group (1.46g crude drug / kg / day).

[0118] High-dose group of Baoji oral liquid extract: Accurately measure 1 mL of Baoji extract (density 1.2 g / mL, crude drug content 4.8 g / mL), add 3.3 mL of physiological saline to prepare a 1.46 g / mL solution, and then dilute with physiological saline to 146 mg / mL; Medium-dose group of Baoji oral liquid extract: Take 50 mL of the high-dose group solution and add 50 mL of physiological saline to prepare a 73 mg / mL solution; Low-dose group of Baoji oral liquid extract: Take the medium-dose group solution and dilute it in half to prepare a 36.5 mg / mL solution. All the above different doses of the drug solution were administered by single gavage at a dose of 0.1 mL / 10 g.

[0119] The solvent for preparing the medicine solution is physiological saline. It should be prepared fresh each time it is needed and temporarily stored at 4°C for later use.

[0120] 2.2 Animal grouping, administration, and tissue sampling

[0121] 2.2.1 Animal grouping and drug intervention

[0122] Mice were quarantined, weighed, and then caged, and acclimatized for three days. They were randomly divided into 11 groups, with 8 mice in each group. The specific groups are as follows: normal group, model group, positive control mosapride citrate tablets (comparative example 1) group, positive control Huoxiang Zhengqi capsules (comparative example 2) group, low-dose Baoji oral liquid extract group (Example 1), medium-dose Baoji oral liquid extract group (Example 1), high-dose Baoji oral liquid extract group (Example 1), medium-dose group of Example 2, medium-dose group of Example 3, medium-dose group of Comparative example 3, and medium-dose group of Comparative example 4.

[0123] Except for the normal group, all other groups were intraperitoneally injected with cisplatin for 4 days (2 mg / kg / day) to establish the model. A significant decrease in food intake starting on day 3 indicated successful modeling. The normal group received an equal volume of physiological saline intraperitoneally. All mice were fed standard diets and had free access to water.

[0124] Four days after modeling, starting on day 5, the treatment groups were administered different doses of the drug solution by gavage: Mosapride citrate tablets: 20 mg / kg / day; Huoxiang Zhengqi capsules: 264 mg / kg / day; Low-dose group of Baoji oral liquid extract (Example 1): 365 mg crude drug / kg / day; Medium-dose group of Baoji oral liquid extract (Example 1): 730 mg crude drug / kg / day; High-dose group of Baoji oral liquid extract (Example 1): 1460 mg crude drug / kg / day; Medium-dose groups of Examples 2-3 and Comparative Examples 3-4: 730 mg crude drug / kg / day. The control group and model group were administered an equal volume of physiological saline by gavage once a day for five consecutive days. All mice were fed standard feed and had free access to water. After the last gavage, the mice were fasted for 24 hours but had free access to water.

[0125] 2.2.2 Gastric emptying and intestinal propulsion experiment

[0126] Mice were given 0.4 mL (g) of semi-solid nutritional paste after fasting for 24 hours. Twenty minutes later, the mice were euthanized and the cardia and pylorus were ligated. The total and net weight of the stomach were measured, and the total length of the small intestine and the distance from the front of the solid paste to the pylorus were recorded. The gastric emptying rate and intestinal propulsion rate were calculated.

[0127] 2.2.3 Collection of serum and tissue samples

[0128] Blood was collected from the mice by enucleation of the eyeballs. After standing at room temperature for 1 hour, the blood was centrifuged (centrifuge parameters 3000 rpm, 10 min). The supernatant serum was separated and stored at -80°C for later use. Stomach tissue from the mice was cut and placed into cryovials and stored at -80°C for later use.

[0129] 2.3 Hematoxylin and eosin staining analysis of gastric antrum tissue

[0130] Tissue samples were taken from the same location in the gastric antrum of mice in each group, fixed with 4% paraformaldehyde, prepared into paraffin sections, stained with hematoxylin and eosin as usual, and observed under a microscope (×100) to observe the histopathological condition of the gastric antrum.

[0131] 2.4 Detection of serum and tissue biochemical markers in mice

[0132] Enzyme-linked immunosorbent assay (ELISA) was used to re-thaw the serum and tissue samples stored in "2.2.3 Collection of Serum and Tissue Samples". The kit was removed from the refrigerator beforehand and allowed to equilibrate to room temperature. The expression levels of gastrin (GAS) and motilin (MTL) in mouse serum and interleukin-4 (IL-4) and interleukin-1β (IL-1β) in mouse gastric tissue were detected according to the kit's instructions.

[0133] 3. Experimental Results

[0134] 3.1 Effects on functional dyspepsia in young mice

[0135] 3.1.1 Effects on body weight of young mice with functional dyspepsia

[0136] like Figure 2 As shown in Table 3, the weight gain of mice in the model group was slow during the modeling period (2-4 days). From day 3, the weight of mice in the model group was significantly reduced compared with the normal group (p<0.05). The weight of mice in the model group recovered and increased during days 5-9 of the experiment. The weight of mice in the model group was significantly different from that in the normal group (p<0.001).

[0137] During the drug administration period (days 5-9 of the experiment), mice in the mosapride citrate tablet group and the low, medium, and high dose groups of Baoji oral liquid extract recovered their weight more quickly. The weight of the model group mice was significantly different from that of the normal group (p < 0.001). During the drug administration period (days 5-9 of the experiment), mice in the mosapride citrate tablet group and the low, medium, and high dose groups of Baoji oral liquid extract recovered their weight more quickly, and the daily weight of these groups was statistically different from that of the model group from day 6 onwards (p < 0.05). The weight recovery of mice in the Huoxiang Zhengqi capsule group was slower, and there was no statistically significant difference in weight between this group and the model group.

[0138] Table 3. Mouse weight statistics

[0139]

[0140] Figure 2 And in Table 3, # P < 0.05 ## P < 0.01, ### P < 0.001, compared with the normal group; *P < 0.05, **P < 0.01, ***P < 0.001, compared with the model group.

[0141] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Low-dose Baoji oral liquid extract group (Example 1); BJM: Medium-dose Baoji oral liquid extract group (Example 1); BJH: High-dose Baoji oral liquid extract group (Example 1).

[0142] Compared with the model group, the Mosa group showed significant differences in mouse body weight on days 6, 7, 8, and 9 (p < 0.01, p < 0.05). The BJL group showed significant differences in mouse body weight compared with the model group on days 6, 7, and 8 (p < 0.05). The BJM group showed significant differences in mouse body weight compared with the model group on days 6, 7, 8, and 9 (p < 0.05). The BJH group showed statistically significant differences in mouse body weight compared with the model group on days 6, 7, 8, and 9 (p < 0.01, p < 0.05).

[0143] The experimental animals used in this invention are young mice, whose weight naturally increases rapidly during growth; however, during the continuous modeling process, weight gain slows down due to functional dyspepsia.

[0144] 3.1.2 Effect on food intake in young mice with functional dyspepsia

[0145] like Figure 3As shown, the Baoji oral liquid composition can promote a steady recovery in the food intake of young mice with functional dyspepsia, and by the third day of administration (day 7 of the experiment), the food intake can be restored to a level comparable to that of the normal group. Figure 3 In the bar chart, the food intake on day 5, day 6, and day 7 of the experiment is shown from bottom to top.

[0146] 3.1.3 Effect on gastric emptying rate in young mice with functional dyspepsia

[0147] like Figure 4 As shown, compared with the normal group, the gastric emptying rate of mice in the model group was significantly reduced (p < 0.001). Compared with the model group, the gastric emptying rate of mice in the mosapride citrate tablet group was significantly increased (p < 0.001); the gastric emptying rate of mice in the Huoxiang Zhengqi capsule group, the low, medium and high dose groups of Baoji oral liquid extract, the Example 2 group and the Example 3 group were significantly increased (p < 0.01); there was no statistically significant difference in the gastric emptying rate of mice in the Comparative Example 3 and Comparative Example 4 groups.

[0148] Figure 4 middle, ### P < 0.001, compared with the normal group; **P < 0.01, ***P < 0.001, compared with the model group.

[0149] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Low-dose Baoji oral liquid extract group (Example 1); BJM: Medium-dose Baoji oral liquid extract group (Example 1); BJH: High-dose Baoji oral liquid extract group (Example 1); S2: Medium-dose group of Example 2; S3: Medium-dose group of Example 3; D3: Medium-dose group of Comparative Example 3; D4: Medium-dose group of Comparative Example 4.

[0150] 3.1.4 Effect on intestinal propulsion rate in young mice with functional dyspepsia

[0151] like Figure 5 As shown, compared with the normal group, the intestinal propulsion rate of mice in the model group was significantly reduced (p < 0.01). Compared with the model group, the intestinal propulsion rate of mice in the mosapride citrate tablet group, the Huoxiang Zhengqi capsule group, the medium-dose group of Baoji oral liquid extract, the Example 2 group, and the Example 3 group was significantly increased (p < 0.05); the intestinal propulsion rate of mice in the high-dose group of Baoji oral liquid extract was significantly increased (p < 0.001); there was no statistically significant difference in the intestinal propulsion rate of mice in the low-dose group of Baoji oral liquid extract, the Comparative Example 3 group, and the Comparative Example 4 group.

[0152] Figure 5 middle, ##P < 0.01, compared with the normal group; *P < 0.05, ***P < 0.001, compared with the model group.

[0153] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Low-dose Baoji oral liquid extract group (Example 1); BJM: Medium-dose Baoji oral liquid extract group (Example 1); BJH: High-dose Baoji oral liquid extract group (Example 1); S2: Medium-dose group of Example 2; S3: Medium-dose group of Example 3; D3: Medium-dose group of Comparative Example 3; D4: Medium-dose group of Comparative Example 4.

[0154] 3.2 Analysis of hematoxylin and eosin staining results of gastric antrum tissue

[0155] like Figure 6 As shown, the normal group mice exhibited normal gastric antral tissue morphology, with clear mucosal and muscular layers, and tightly and orderly arranged glands, without inflammatory cells or obvious organic changes. In the model group mice, inflammatory cell infiltration was observed in the gastric antral mucosa, with significant edema in the submucosa and lamina propria, and loose connective tissue arrangement. In the drug-treated groups, only a small amount of inflammatory cell infiltration was observed in the gastric antral mucosa, with no other significant pathological damage.

[0156] Figure 6 In the group, N: normal group; FD: model group; Mosa: mosapride group; HX: Huoxiang Zhengqi capsule group; BJL: low-dose Baoji oral liquid extract group; BJM: medium-dose Baoji oral liquid extract group; BJH: high-dose Baoji oral liquid extract group.

[0157] 3.3 Effects on the expression of serum and gastric tissue biomarkers in mice with functional dyspepsia

[0158] To clarify the effect of the Baoji oral liquid composition on the expression of serum and gastric tissue biomarkers in young mice with functional dyspepsia, this experiment measured the expression levels of gastrin (GAS) and motilin (MTL) in mouse serum, and the expression levels of interleukin-4 (IL-4) and interleukin-1β (IL-1β) in mouse gastric tissue.

[0159] 3.3.1 Gastrin (GAS)

[0160] like Figure 7As shown, compared with the normal group, the expression level of gastrin in the serum of mice in the model group was significantly reduced (p<0.001); compared with the model group, the expression level of gastrin in the serum of mice in the mosapride citrate tablet group, the low, medium and high dose groups of Baoji oral liquid extract, the Example 2 group and the Example 3 group was significantly increased (p<0.01, p<0.05); there was no statistically significant difference in the expression level of gastrin in the serum of mice in the Huoxiang Zhengqi capsule group, the comparative example 3 group and the comparative example 4 group.

[0161] Figure 7 middle, ### P < 0.001, compared with the normal group; *P < 0.05, **P < 0.01, compared with the model group.

[0162] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Low-dose Baoji oral liquid extract group (Example 1); BJM: Medium-dose Baoji oral liquid extract group (Example 1); BJH: High-dose Baoji oral liquid extract group (Example 1); S2: Medium-dose group of Example 2; S3: Medium-dose group of Example 3; D3: Medium-dose group of Comparative Example 3; D4: Medium-dose group of Comparative Example 4.

[0163] 3.3.2 Motilin (MTL)

[0164] like Figure 8 As shown, compared with the normal group, the motilin expression level in the serum of mice in the model group was significantly reduced (p<0.001); compared with the model group, the motilin expression levels in mice in the mosapride citrate tablet group and the low, medium and high dose groups of Baoji oral liquid extract were significantly increased (p<0.001, p<0.01, p<0.05), and the pharmacological effect of the Baoji oral liquid composition showed a dose-dependent relationship; the motilin expression levels in mice in Example 2 and Example 3 groups were significantly increased (p<0.01); there was no statistically significant difference in the motilin expression levels in mice in Comparative Example 3 and Comparative Example 4 groups.

[0165] Figure 8 middle, ### P < 0.001, compared with the normal group; *P < 0.05, **P < 0.01, ***P < 0.001, compared with the model group.

[0166] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Low-dose Baoji oral liquid extract group (Example 1); BJM: Medium-dose Baoji oral liquid extract group (Example 1); BJH: High-dose Baoji oral liquid extract group (Example 1); S2: Medium-dose group of Example 2; S3: Medium-dose group of Example 3; D3: Medium-dose group of Comparative Example 3; D4: Medium-dose group of Comparative Example 4.

[0167] 3.3.3 Interleukin-4 (IL-4)

[0168] like Figure 9 As shown, compared with the normal group, the expression level of IL-4 in the gastric tissue of mice in the model group was significantly reduced (p<0.01); compared with the model group, the expression level of IL-4 in the gastric tissue of mice in the Huoxiang Zhengqi Capsule group and the low-dose group of Baoji Oral Liquid Extract was significantly increased (p<0.05), and the expression level of IL-4 in the gastric tissue of mice in the medium-dose group of Baoji Oral Liquid Extract was extremely significantly increased (p<0.001); the expression level of IL-4 in the gastric tissue of mice in the medium-high dose group of Baoji Oral Liquid Extract, the Example 2 group and the Example 3 group was significantly increased (p<0.01); the expression level of IL-4 in the gastric tissue of mice in the Comparative Example 3 group and the Comparative Example 4 group was significantly increased (p<0.05).

[0169] Figure 9 middle, ## P < 0.01, compared with the normal group; *P < 0.05, **P < 0.01, ***P < 0.001, compared with the model group.

[0170] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Low-dose Baoji oral liquid extract group (Example 1); BJM: Medium-dose Baoji oral liquid extract group (Example 1); BJH: High-dose Baoji oral liquid extract group (Example 1); S2: Medium-dose group of Example 2; S3: Medium-dose group of Example 3; D3: Medium-dose group of Comparative Example 3; D4: Medium-dose group of Comparative Example 4.

[0171] 3.3.4 Interleukin (IL-1β)

[0172] like Figure 10As shown, compared with the normal group, the expression level of interleukin-1β in the gastric tissue of mice in the model group was extremely significantly increased (p<0.001); compared with the model group, the expression level of interleukin-1β in the mosapride citrate tablet group was significantly decreased (p<0.01). In the low, medium, and high dose groups of Baoji Koufuye extract, and in the groups of Example 2 and Example 3, there was a tendency for the expression level of interleukin-1β in the gastric tissue of mice to decrease, but there was no significant difference compared with the model group; compared with the model group, there was no significant difference in the expression level of interleukin-1β in the Huoxiang Zhengqi Capsule group, the groups of Comparative Example 3 and Comparative Example 4 in the gastric tissue of mice.

[0173] Figure 10 in ### P<0.001, compared with the normal group; **P<0.01, compared with the model group.

[0174] N: normal group; FD: model group; Mosa: mosapride citrate tablet group (Comparative Example 1); HX: Huoxiang Zhengqi Capsule group (Comparative Example 2); BJL: low dose group of Baoji Koufuye extract (Example 1); BJM: medium dose group of Baoji Koufuye extract (Example 1); BJH: high dose group of Baoji Koufuye extract (Example 1); S2: medium dose group of Example 2; S3: medium dose group of Example 3; D3: medium dose group of Comparative Example 3; D4: medium dose group of Comparative Example 4.

[0175] Experiment 2: Experiment on inducing functional dyspepsia in ICR mice with loperamide

[0176] A mouse model of functional dyspepsia was induced by loperamide, and different concentrations of Baoji Koufuye composition (extract) and the positive drug mosapride citrate tablets were administered by gavage. The gastric emptying rate, intestinal propulsion rate, and the expression levels of serum and tissue biochemical indexes of mice were measured. The effect of Baoji Koufuye on the mouse model of loperamide-induced functional dyspepsia was investigated. The experimental results showed that the therapeutic effect of Baoji Koufuye on mice with loperamide-induced functional dyspepsia was general, and there was no significant difference compared with the model group.

[0177] 1. Experimental materials

[0178] 1.1 Experimental animals

[0179] Male ICR mice, 3 - 4 weeks old, weighing 12 - 15 g, license number: SCXK(Guangdong)2022 - 0002. The animals were fed freely and adaptively raised for three days under the conditions of a temperature of 25±0.5℃, a relative humidity of 55±5%, and alternating light (12h light-dark cycle). During the process of this study, the experiments were carried out strictly in accordance with the requirements of experimental animal protection and ethics.

[0180] 1.2 Experimental reagents

[0181] Same as Experiment 1, cisplatin-induced functional dyspepsia in mice.

[0182] 1.3 Experimental Apparatus

[0183] Same as Experiment 1, cisplatin-induced functional dyspepsia in mice.

[0184] 2. Experimental Methods

[0185] 2.1 Preparation of drug solution

[0186] Same as Experiment 1, cisplatin-induced functional dyspepsia in mice.

[0187] 2.2 Animal grouping, administration, and tissue sampling

[0188] 2.2.1 Animal grouping and drug intervention

[0189] Mice were quarantined, weighed, and then caged, and acclimatized for 7 days. They were randomly divided into 5 groups of 8 mice each. The specific groups are as follows: normal group, model group, positive control mosapride citrate tablets (comparative example 1) group, medium-dose Baoji oral liquid extract group (Example 1), and high-dose Baoji oral liquid extract group (Example 1).

[0190] From day 1 to day 7, normal mice were administered 0.2 mL of sterile saline by gavage daily, while other groups were administered loperamide (10 mg / kg, 0.2 mL) by gavage to establish a functional dyspepsia mouse model. From day 8 to day 12, the normal group was administered 0.2 mL of sterile saline by gavage, while the other groups were administered loperamide (10 mg / kg, 0.2 mL) by gavage. One hour after gavage, the positive control group was administered mosapride citrate tablets 20 mg / kg / day, the model group was administered sterile saline 0.2 mL, the medium-dose group of Baoji oral liquid extract was administered 730 mg crude drug / kg / day of Baoji oral liquid extract (Example 1), and the high-dose group of Baoji oral liquid extract (Example 1) was administered 1460 mg crude drug / kg / day of Baoji oral liquid extract (Example 1). On day 21, after administration of the corresponding drugs by gavage, gastric emptying rate, intestinal propulsion rate, and serum and tissue biochemical index levels were measured.

[0191] 2.2.2 Gastric emptying and intestinal propulsion experiment

[0192] Same as Experiment 1, cisplatin-induced functional dyspepsia in mice.

[0193] 2.2.3 Collection of serum and tissue samples

[0194] Same as Experiment 1, cisplatin-induced functional dyspepsia in mice.

[0195] 2.3 Detection of serum and tissue biochemical markers in mice

[0196] Same as Experiment 1, cisplatin-induced functional dyspepsia in mice.

[0197] 3. Experimental Results

[0198] 3.1 Effects on functional dyspepsia in young mice

[0199] 3.1.1 Effect on gastric emptying rate in young mice with functional dyspepsia

[0200] like Figure 11 As shown, compared with the normal group, the gastric emptying rate of mice in the model group was significantly reduced (p < 0.001). Compared with the model group, the gastric emptying rate of mice in the mosapride citrate tablet group was significantly increased (p < 0.01); the gastric emptying rate of the medium and high dose groups of Baoji oral liquid extract did not increase significantly.

[0201] Figure 11 middle, ### P < 0.001, compared with the normal group; **P < 0.01, compared with the model group.

[0202] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); BJM: Medium dose group of Baoji oral liquid extract (Example 1); BJH: High dose group of Baoji oral liquid extract (Example 1).

[0203] 3.1.2 Effect on intestinal propulsion rate in young mice with functional dyspepsia

[0204] like Figure 12 As shown, compared with the normal group, the intestinal propulsion rate of mice in the model group was significantly reduced (p < 0.001). Compared with the model group, the intestinal propulsion rate of mice treated with mosapride citrate tablets was significantly increased (p < 0.05), while the gastric emptying rate of mice in the medium and high dose groups of Baoji oral liquid extract was not significantly increased.

[0205] Figure 12 middle, ### P < 0.001, compared with the normal group; *P < 0.05, compared with the model group.

[0206] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); BJM: Medium dose group of Baoji oral liquid extract (Example 1); BJH: High dose group of Baoji oral liquid extract (Example 1).

[0207] 3.2 Effects on the expression of serum and gastric tissue biomarkers in mice with functional dyspepsia

[0208] 3.2.1 Gastrin (GAS)

[0209] like Figure 13As shown, compared with the normal group, the expression level of gastrin in the serum of mice in the model group was significantly reduced (p<0.001); compared with the model group, the expression level of gastrin in the serum of mice in the mosapride citrate tablet group was significantly increased (p<0.05), while the expression level of gastrin in mice in the Baoji oral liquid extract group did not change significantly.

[0210] Figure 13 middle, ### P < 0.001, compared with the normal group; *P < 0.05, compared with the model group.

[0211] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); BJM: Medium dose group of Baoji oral liquid extract (Example 1); BJH: High dose group of Baoji oral liquid extract (Example 1).

[0212] 3.2.2 Motilin (MTL)

[0213] like Figure 14 As shown, compared with the normal group, the motilin expression level in the serum of mice in the model group was significantly reduced (p<0.001); compared with the model group, the motilin expression level in mice in the mosapride citrate tablet group was significantly increased (p<0.05), while the motilin expression level in mice in the Baoji oral liquid extract group did not increase significantly.

[0214] Figure 14 middle, ### P < 0.001, compared with the normal group; *P < 0.05, compared with the model group.

[0215] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); BJM: Medium dose group of Baoji oral liquid extract (Example 1); BJH: High dose group of Baoji oral liquid extract (Example 1).

[0216] 3.2.3 Interleukin-4 (IL-4)

[0217] like Figure 15 As shown, compared with the normal group, the expression level of IL-4 in the gastric tissue of mice in the model group was significantly reduced (p<0.001); compared with the model group, there was no significant difference in the expression level of IL-4 in mice in the mosapride citrate tablet group, while the expression level of IL-4 in the gastric tissue of mice in the medium and high dose groups of Baoji oral liquid extract was significantly increased (p<0.05).

[0218] Figure 15 middle, ### P < 0.001, compared with the normal group; *P < 0.05, compared with the model group.

[0219] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); BJM: Medium dose group of Baoji oral liquid extract (Example 1); BJH: High dose group of Baoji oral liquid extract (Example 1).

[0220] 3.2.4 Interleukin (IL-1β)

[0221] like Figure 16 As shown, compared with the normal group, the expression level of interleukin 1β in the gastric tissue of mice in the model group was significantly increased (p<0.001); compared with the model group, the expression level of interleukin 1β in mice in the mosapride citrate tablet group was significantly decreased (p<0.01); the expression level of interleukin 1β in the Baoji oral liquid composition showed a decreasing trend, but there was no significant difference compared with the model group.

[0222] Figure 16 middle, ### P < 0.001, compared with the normal group; **P < 0.01, compared with the model group.

[0223] N: Normal group; FD: Model group; Mosa: Mosapride citrate tablet group (Comparative Example 1); BJM: Medium dose group of Baoji oral liquid extract (Example 1); BJH: High dose group of Baoji oral liquid extract (Example 1).

[0224] A mouse model of functional dyspepsia induced by loperamide was used. The Baoji oral liquid composition was administered by gavage. The results showed that the Baoji oral liquid composition had poor therapeutic effect on young mice with loperamide-induced functional dyspepsia, and even showed no significant difference compared to the model group. Therefore, the Baoji oral liquid of this invention has no effect on the treatment of loperamide-induced functional dyspepsia.

[0225] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. The application of the Baoji oral liquid composition in the preparation of a drug for treating cisplatin-induced functional dyspepsia; The treatment for cisplatin-induced functional dyspepsia includes: It can improve gastric emptying rate, intestinal propulsion rate, and serum gastrin and motilin expression levels. The Baoji oral liquid composition is made from the following raw materials in parts by weight: 2.5-4.5 parts Uncaria rhynchophylla, 4-8 parts Mentha haplocalyx, 2.5-4.5 parts Tribulus terrestris, 10-16 parts Angelica dahurica, 10-16 parts Aucklandia lappa, 10-16 parts Guangdong Shenqu (medicated leaven), 5-8 parts Chrysanthemum morifolium, 10-16 parts Pogostemon cablin, 10-16 parts Atractylodes lancea, 22-36.8 parts Poria cocos, 10-16 parts Magnolia officinalis, 5-8 parts Citrus reticulata peel, 7-14 parts Trichosanthes kirilowii, 14-20.2 parts Coix lacryma-jobi, 10-16 parts Pueraria lobata, and 8-12 parts Oryza sativa sprouts.

2. The application according to claim 1, characterized in that, The treatment for functional dyspepsia includes weight recovery and improved weight gain rate.

3. The application according to claim 1, characterized in that, The treatment of functional dyspepsia includes promoting the recovery of food intake.

4. The application according to claim 1, characterized in that, The treatment for functional dyspepsia includes protecting the gastric mucosa, reducing inflammatory cell infiltration, and repairing the mucosal and muscular layers.

5. The application according to claim 1, characterized in that, The treatment for functional dyspepsia includes increasing IL-4 levels and decreasing IL-1β expression levels in gastric tissue.

6. The application according to claim 1, characterized in that, The drug is administered in combination with one or more other therapeutic agents.

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