Application of Baoji oral liquid composition in preparation of medicines for treating functional dyspepsia

Abstract

The invention provides application of a Baoji oral liquid composition in preparation of a medicine for treating functional dyspepsia, and relates to the technical field of medicines. Based on the Baoji oral liquid, it is found that the Baoji oral liquid has a remarkable effect on treating functional dyspepsia, especially cis-platinum induced functional dyspepsia; specifically, the body weight can be quickly recovered, and the body weight increase is remarkably improved; stable recovery of food intake can be promoted; the gastric emptying rate can be obviously improved, and the intestinal tract propulsion rate is improved; the gastric mucosa layer is protected, inflammatory cell infiltration is reduced, and the mucosa layer and the muscular layer are repaired; the expression of gastrin and motilin in serum can be improved; the expression level of IL-4 in stomach tissues is improved; and the expression level of IL-1beta is reduced. The Baoji oral liquid is applied to preparation of the medicine for treating the functional dyspepsia, and the effect is remarkable.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and specifically relates to the application of a Baoji oral liquid composition in the preparation of a functional dyspepsia drug. Background Art

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

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

[0004] 1. Different definitions:

[0005] Dyspepsia: refers to a group of clinical syndromes with symptoms such as upper abdominal pain, burning sensation, fullness after meals and early satiety, which can be caused by a variety of reasons. Functional dyspepsia: refers to a group of clinical syndromes with upper abdominal pain, upper abdominal fullness, early satiety, belching, loss of appetite, nausea, vomiting, etc. as the main symptoms, after excluding organic diseases. It is one of the common functional gastrointestinal diseases in clinical practice.

[0006] 2. Different causes:

[0007] Causes of dyspepsia: (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 do not meet the diagnostic criteria for functional dyspepsia.

[0008] Causes of functional dyspepsia: The pathogenesis is still not very clear. Studies have shown that it is related to gastrointestinal motility disorders, such as delayed gastric emptying and abnormal gastroduodenal coordinated motility; visceral hypersensitivity; psychological factors, such as anxiety, depression, stress and other emotional factors; Helicobacter pylori infection; genetic factors and other factors.

[0009] 3. Different diagnostic criteria:

[0010] Diagnosis of indigestion: It is necessary to check whether there is organic lesion through medical history inquiry, physical examination, laboratory examination, and imaging examination (such as gastroscopy, abdominal ultrasound, etc.). The diagnostic criteria of functional dyspepsia in Western medicine are: persistent or recurrent upper abdominal pain, upper abdominal burning sensation, postprandial abdominal distension, early satiety, belching, nausea, vomiting, acid reflux, etc.; symptoms cannot be relieved after defecation or the onset of symptoms is not related to changes in defecation frequency and stool characteristics; after evaluation, the symptoms cannot be explained by other diseases. The diagnostic criteria of functional dyspepsia in traditional Chinese medicine include: food stagnation, spleen deficiency and food stagnation, spleen and stomach dampness and heat, liver and stomach disharmony, mixed cold and heat, and spleen and stomach deficiency and cold.

[0011] At present, the drugs and methods for the treatment of FD are roughly divided into acid suppression and antacids, prokinetic drugs, cyproheptadine, psychological intervention, traditional Chinese medicine treatment and microecological preparations. FD is prone to relapse, the main incidence group is young children, and it is not easy to cure. Long-term use of Western medicine is prone to drug resistance and has obvious side effects. Therefore, Chinese medicine treatment has shown unique advantages. The Guidelines for the Clinical Application of Chinese Patent Medicines for the Treatment of Functional Dyspepsia (2021) pointed out that 4 Chinese patent medicines with strong evidence support (Zhizhu Kuanzhong Capsules, Qizhi Weitong Granules, Biling Weitong Granules, Jinghua Weikang Capsules) have the effect of treating FD. However, because the pathological mechanism of functional dyspepsia is unclear, and different drugs have different therapeutic effects on functional dyspepsia with different pathogenesis, more in-depth research is needed on the therapeutic drugs for functional dyspepsia with different pathogenesis.

[0012] In addition, Chinese invention patent CN117357616A discloses a Chinese medicine composition for functional dyspepsia in children, its preparation method and application, wherein the Chinese medicine composition comprises, by weight: 8-54 parts of yam, 5-36 parts of tuckahoe, 5-36 parts of dried orange peel, 5-36 parts of atractylodes macrocephala, 5-36 parts of charred hawthorn, 5-36 parts of stir-fried radish seeds, 5-36 parts of stir-fried malt and 4-18 parts of liquorice. The Chinese medicine composition has a therapeutic effect on functional dyspepsia caused by spleen deficiency induced by rhubarb, functional dyspepsia caused by irregular diet combined with L-arginine in mice, and functional dyspepsia caused by iodoacetamide combined with small platform standing method in rats, and can be used to treat functional dyspepsia in children caused by spleen and stomach weakness in children.

[0013] Chinese invention patent CN102240369A discloses a traditional Chinese medicine preparation for treating functional dyspepsia, which selects Chinese herbal medicines that have the functions of strengthening the spleen and consolidating the foundation, nourishing the earth and replenishing qi, and harmonizing the stomach and promoting descending: red peony root, white atractylodes, cimicifuga, stir-fried barley sprouts, Poria, astragalus, cinnamon twig, chrysanthemum, fennel, costus root, immature bitter orange, areca nut, prickly ash, angelica and radish seeds, which are decocted into a decoction for patients to take.

[0014] Baoji oral liquid is composed of 16 medicinal materials such as Uncaria rhynchophylla. The product has the functions of dispelling exterior pathogens, removing dampness, and harmonizing the middle. It is used to treat abdominal pain, vomiting, diarrhea, choking, belching, nausea and vomiting, gastrointestinal discomfort, indigestion, seasickness, colds of all seasons, fever and headache. Although there are many studies on Chinese medicine preparations for the treatment of functional dyspepsia in the prior art, there is no relevant research and application on the use of Baoji oral liquid in the preparation of drugs for the treatment of cisplatin-induced functional dyspepsia. Summary of the invention

[0015] In view of the problems existing in the prior art, the present invention provides an application of a Baoji oral liquid composition in the preparation of a functional dyspepsia drug; based on the components and preparation method of the Baoji oral liquid, the obtained Baoji oral liquid has a significant therapeutic effect on the treatment of functional dyspepsia, especially cisplatin-induced functional dyspepsia, and provides a new approach for the selection of drugs for the treatment of functional dyspepsia.

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

[0017] In one aspect, 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 restoration of body weight and significant improvement in body weight gain.

[0019] Preferably, said treating functional dyspepsia comprises promoting steady recovery of food intake.

[0020] Preferably, said treating functional dyspepsia comprises significantly increasing the gastric emptying rate.

[0021] Preferably, said treating functional dyspepsia comprises significantly increasing the 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 comprises significantly increasing the expression levels of IL-4 and decreasing IL-1β in gastric tissue.

[0025] Further preferably, the treatment of functional dyspepsia is the treatment of functional dyspepsia induced by cisplatin.

[0026] Preferably, in the application, the drug includes the components in the Baoji Oral Liquid composition, or can be administered in combination with one or more other therapeutic agents.

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

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

[0029] In the present invention, the type and manufacturer of the pharmaceutically acceptable carrier have no significant impact on the technical effect of the drug.

[0030] In the present invention, the pharmaceutically acceptable carrier can be starch, dextrin, sucrose, milk powder, sweetener, mannitol, lactose, cellulose and its derivatives, calcium carbonate, cyclodextrin, β-cyclodextrin, phospholipid materials, magnesium stearate, talc, and flavors.

[0031] Preferably, in the application, the administration of the drug includes oral, sublingual, oral mucosal, intravenous, intramuscular, intraperitoneal, subcutaneous, transdermal, nasal and rectal routes.

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

[0033] Preferably, in the application, the dosage form of the drug includes powders, tablets, granules, pills, hard capsules or soft capsules, creams, ointments, plasters, gels, pastes, powders, patches, solutions, suspensions, injections, syrups, liniments, emulsions, tinctures, elixirs, aerosols and sprays.

[0034] On the other hand, the present invention provides a medicine for treating functional dyspepsia, the components of which include the components in the Baoji oral liquid composition; the components in the Baoji oral liquid composition include: Uncaria rhynchophylla, mint, tribulus terrestris, angelica dahurica, costus root, Guangdong Shenqu, chrysanthemum, patchouli, atractylodes, poria, magnolia bark, tangerine peel, root of trichosanthes, coix seed, kudzu root and rice sprouts.

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

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

[0037] In the present invention, the raw materials of the Baoji oral liquid composition include components: Uncaria rhynchophylla, mint, tribulus terrestris, angelica dahurica, costusroot, Guangdong Shenqu, chrysanthemum, patchouli, atractylodes, tuckahoe, magnolia bark, tangerine peel, radix trichosanthis, coix seed, kudzu root and rice sprout.

[0038] Or the Baoji oral liquid composition is a product prepared by the components, proportions and preparation methods recorded in the prior patent CN100998782A, or a product prepared by the components, proportions and preparation methods recorded in the 2020 edition of the "Chinese Pharmacopoeia".

[0039] Preferably, the raw materials of the Baoji oral liquid composition include the following components, measured by weight: 2.5-4.5 parts of Uncaria rhynchophylla, 4-8 parts of Mentha arvense, 2.5-4.5 parts of Tribulus terrestris, 10-16 parts of Angelica dahurica, 10-16 parts of Costusroot rhizome, 10-16 parts of Guangdong Shenqu, 5-8 parts of Chrysanthemum, 10-16 parts of Patchouli, 10-16 parts of Atractylodes lancea, 22-36.8 parts of Poria, 10-16 parts of Magnolia officinalis, 5-8 parts of Citrus aurantium, 7-14 parts of Radix Trichosanthis, 14-20.2 parts of Coix seeds, 10-16 parts of Pueraria root and 8-12 parts of Rice sprouts.

[0040] In the embodiment of the present invention, the Baoji oral liquid composition used is the Baoji oral liquid extract. The raw materials thereof, in terms of weight, are as follows: 3.4 parts of Uncaria rhynchophylla, 6.8 parts of Mentha arvense, 3.4 parts of Tribulus terrestris, 13.6 parts of Angelica dahurica, 13.6 parts of Aucklandia lappa, 13.6 parts of Guangdong Shenqu, 6.8 parts of Chrysanthemum, 13.6 parts of Patchouli, 13.6 parts of Atractylodes lancea, 27.3 parts of Poria, 13.6 parts of Magnolia officinalis, 6.8 parts of Citrus aurantium, 10.2 parts of Radix Trichosanthis, 17.1 parts of Coix seeds, 13.6 parts of Pueraria root and 10.2 parts of Rice sprouts;

[0041] The preparation method is as follows: the above 16 herbs, costusroot, atractylodes, mint, patchouli, and red tangerine peel are steam distilled for 2 hours, and the volatile oil is collected and stored in another container; the residues and the aqueous solution after oil extraction are decocted twice with water, each time for 1.5 hours, the decoction is filtered, the filtrate is combined, and concentrated to a relative density of 1.08-1.12 (60°C), cooled, ethanol is added to make the alcohol content reach 45% (volume concentration), let stand overnight, filter, recover ethanol, and concentrate into an extract for standby use; Uncaria rhynchophylla, Tribulus terrestris, chrysanthemum, 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 decoction is combined, filtered, and the filtrate is concentrated to a relative density of 1.02-1.05 (60°C), cooled, ethanol is added to make the alcohol content reach 40% (volume concentration) Volume concentration), let stand overnight, filter, recover ethanol and concentrate into extract II for standby use; take coix seed and rice sprout, add water and boil twice, each time for 1 hour, combine the decoction, filter, concentrate the filtrate to a relative density of 1.02-1.05 (60°C), let cool, add ethanol to make the alcohol content reach 45% (volume concentration), let stand overnight, filter, recover ethanol, and concentrate into extract III for standby use; take Poria, Radix Trichosanthis, Angelica dahurica, and Radix Puerariae, add water and boil twice, the first time for 2 hours, the second time for 1 hour, combine the decoction, filter, concentrate the filtrate to a relative density of 1.02-1.05 (60°C), let cool: add ethanol to make the alcohol content reach 60% (volume concentration), let stand overnight, filter, recover ethanol, and concentrate into extract IV for standby use. The above extracts are stirred evenly and sterilized to obtain the Baoji oral liquid composition (extract).

[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 drugs for treating functional dyspepsia, which can quickly restore the body weight of mice with functional dyspepsia caused by cisplatin injection, and significantly increase body weight gain; significantly improve gastric emptying rate and intestinal propulsion rate, protect the gastric antral mucosal layer, reduce inflammatory cell infiltration, and repair the mucosal layer.

[0044] 2. The Baoji oral liquid composition of the present invention has a significant effect in treating functional dyspepsia compared to other prescriptions with similar components; it can significantly promote the rapid recovery of body weight and food intake of mice with functional dyspepsia induced by cisplatin; it can significantly improve the gastric emptying rate and intestinal propulsion rate of 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 reduce the expression level of IL-1β. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1This is the animal experiment flow chart of the cisplatin-induced functional dyspepsia model in mice.

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

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

[0049] Figure 4 This is a comparison chart of gastric emptying rates of mice in each group of the cisplatin-induced functional dyspepsia model in mice.

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

[0051] Figure 6 This is a comparison of HE staining of sinus tissues of mice in each group of the cisplatin-induced functional dyspepsia model in mice, with a magnification of 100 times.

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

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

[0054] Fig. 9 This is a comparison chart of interleukin-4 levels in gastric tissue of mice in each group of the cisplatin-induced functional dyspepsia model in mice.

[0055] Fig.10 This is a comparison chart of interleukin-1β levels in gastric tissue of mice in each group of the cisplatin-induced functional dyspepsia model in mice.

[0056] Fig.11 This is a comparison chart of the gastric emptying rates of mice in each group of the loperamide-induced functional dyspepsia model in mice.

[0057] Fig.12 This is a comparative chart of the intestinal propulsion rates of mice in each group of the loperamide-induced functional dyspepsia model in mice.

[0058] Fig.13 This is a comparison chart of serum gastrin levels in each group of mice in the loperamide-induced functional dyspepsia model in mice.

[0059] Fig.14 This is a comparison chart of serum motilin levels in each group of mice in the loperamide-induced functional dyspepsia model in mice.

[0060] Fig.15 This is a comparison chart of interleukin-4 levels in gastric tissue of mice in each group of the loperamide-induced functional dyspepsia model in mice.

[0061] Fig.16 This is a comparison of interleukin-1β levels in gastric tissue of mice in each group of the loperamide-induced functional dyspepsia model in mice. DETAILED DESCRIPTION

[0062] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is merely an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of the present invention.

[0063] When the embodiments give numerical ranges, it should be understood that, unless otherwise specified in the present invention, both endpoints of each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used in the present invention have the same meanings as those generally understood by those of ordinary skill in the art to which the present invention belongs.

[0064] The present invention is further described below by way of specific examples. The various chemical reagents used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified. Products from different manufacturers have no significant effect on the effects.

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

[0066] Basic Example

[0067] The Baoji oral liquid composition is prepared from the following raw materials: 2.5-4.5 parts of Uncaria rhynchophylla, 4-8 parts of Mentha arvense, 2.5-4.5 parts of Tribulus terrestris, 10-16 parts of Angelica dahurica, 10-16 parts of Costusroot rhizome, 10-16 parts of Guangdong Shenqu, 5-8 parts of Chrysanthemum, 10-16 parts of Patchouli, 10-16 parts of Atractylodes lancea, 22-36.8 parts of Poria, 10-16 parts of Magnolia officinalis, 5-8 parts of Citrus aurantium, 7-14 parts of Radix Trichosanthis, 14-20.2 parts of Coix seeds, 10-16 parts of Pueraria root and 8-12 parts of Rice sprouts.

[0068] The preparation method of Baoji oral liquid extract (Baoji oral liquid composition) is as follows:

[0069] The above-mentioned five medicinal materials of costusroot, atractylodes, mint, patchouli and red tangerine peel are combined, soaked in 0.5-2 times water for 0.5-2 hours, steam distilled for 1-3 hours, and volatile oil is collected and stored in another container; the medicinal residues are decocted with water for 1-3 times, each decocting for 1-2 hours, the decoction is combined, filtered, and the filtrate is concentrated to a relative density of 1.04-1.20 at 45° C.-75° C., cooled, ethanol is added to make the alcohol content reach 40%-55% (volume concentration), allowed to stand for 4-36 hours, filtered, and ethanol is recovered; concentrated to a relative density of 1.25-1.45 at 45° C.-75° C. to obtain an extract, which is reserved;

[0070] Combine the above five medicinal materials of Uncaria rhynchophylla, Tribulus terrestris, Chrysanthemum, Magnolia officinalis and Guangdong Shenqu, add water and boil for 1-3 times, each time boiling for 1-3 hours, combine the decoctions, filter, concentrate the filtrate to a relative density of 1.02-1.05 at 45° C.-75° C., cool, add ethanol to make the alcohol content reach 30%-50% (volume concentration), let stand for 4-36 hours, filter, recover ethanol; concentrate to a relative density of 1.05-1.10 at 45° C.-75° C., obtain extract II, and set aside;

[0071] Combine the above coix seeds and rice sprouts, add water and boil for 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°C-75°C, cool, add ethanol to make the alcohol content reach 35%-55% (volume concentration), let stand for 4-36 hours, filter, recover ethanol; concentrate to a relative density of 1.05-1.10 at 45°C-75°C, obtain extract III, and set aside;

[0072] Combine the above four medicinal materials of Poria cocos, Radix Trichosanthis, Radix Angelicae Dahuricae and Radix Puerariae, add water and boil for 1-3 times, each time boiling for 0.5-3 hours, combine the decoctions, filter, concentrate the filtrate to a relative density of 1.01-1.15 at 45°C-75°C, cool, add ethanol to make the alcohol content reach 50%-70% (volume concentration), let stand for 4-36 hours, filter, recover ethanol; concentrate to a relative density of 1.02-1.20 at 45°C-75°C, obtain extract IV, and set aside;

[0073] The above extracts are stirred evenly and sterilized to obtain the Baoji oral liquid extract.

[0074] The technical solutions within the scope of the above basic embodiments can all achieve the technical effects described in the present invention and achieve significant therapeutic effects on cisplatin-induced functional dyspepsia in mice.

[0075] Example 1

[0076] The raw materials of Baoji oral liquid extract are as follows: 3.4 parts of Uncaria rhynchophylla, 6.8 parts of Mentha arvense, 3.4 parts of Tribulus terrestris, 13.6 parts of Angelica dahurica, 13.6 parts of Aucklandia lappa, 13.6 parts of Guangdong Shenqu, 6.8 parts of Chrysanthemum, 13.6 parts of Patchouli, 13.6 parts of Atractylodes lancea, 27.3 parts of Poria, 13.6 parts of Magnolia officinalis, 6.8 parts of Citrus aurantium, 10.2 parts of Radix Trichosanthis, 17.1 parts of Coix seeds, 13.6 parts of Pueraria root and 10.2 parts of Rice sprouts;

[0077] The preparation method is as follows: the above 16 herbs, costusroot, atractylodes, mint, patchouli, and red tangerine peel are steam distilled for 2 hours, and the volatile oil is collected and stored in another container; the residues and the aqueous solution after oil extraction are decocted twice with water, each time for 1.5 hours, the decoction is filtered, the filtrate is combined, and concentrated to a relative density of 1.08-1.12 (60°C), cooled, ethanol is added to make the alcohol content reach 45% (volume concentration), let stand overnight, filter, recover ethanol, and concentrate into an extract for standby use; Uncaria rhynchophylla, Tribulus terrestris, chrysanthemum, 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 decoction is combined, filtered, and the filtrate is concentrated to a relative density of 1.02-1.05 (60°C), cooled, ethanol is added to make the alcohol content reach 40% (volume concentration) Volume concentration), let stand overnight, filter, recover ethanol and concentrate into extract II for standby use; take coix seed and rice sprout, add water and boil twice, each time for 1 hour, combine the decoction, filter, concentrate the filtrate to a relative density of 1.02-1.05 (60°C), let cool, add ethanol to make the alcohol content reach 45% (volume concentration), let stand overnight, filter, recover ethanol, and concentrate into extract III for standby use; take Poria, Radix Trichosanthis, Angelica dahurica, and Radix Puerariae, add water and boil twice, the first time for 2 hours, the second time for 1 hour, combine the decoction, filter, concentrate the filtrate to a relative density of 1.02-1.05 (60°C), let cool: add ethanol to make the alcohol content reach 60% (volume concentration), let stand overnight, filter, recover ethanol, and concentrate into extract IV for standby use. The above extracts are stirred evenly and sterilized to obtain the Baoji oral liquid composition (extract).

[0078] Example 2

[0079] The raw materials of Baoji oral liquid extract are composed of the following components by weight: 2.5 parts of Uncaria rhynchophylla, 4 parts of peppermint, 2.5 parts of tribulus terrestris, 10 parts of angelica dahurica, 10 parts of costusroot, 10 parts of Guangdong Shenqu, 5 parts of chrysanthemum, 10 parts of patchouli, 10 parts of atractylodes, 22 parts of poria, 10 parts of magnolia bark, 5 parts of citrus aurantium, 7 parts of root of trichosanthes, 14 parts of coix seed, 10 parts of kudzu root and 8 parts of rice 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] The raw materials of Baoji oral liquid extract are composed of the following components by weight: 4.5 parts of Uncaria rhynchophylla, 8 parts of Mentha arvense, 4.5 parts of Tribulus terrestris, 16 parts of Angelica dahurica, 16 parts of Costusroot rhizome, 16 parts of Guangdong Shenqu, 8 parts of Chrysanthemum, 16 parts of Patchouli, 16 parts of Atractylodes lancea, 36.8 parts of Poria, 16 parts of Magnolia officinalis, 8 parts of Citrus aurantium, 14 parts of Radix Trichosanthis, 20.2 parts of Coix seeds, 16 parts of Pueraria root and 12 parts of Rice 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 produced by Yabao Pharmaceutical Group Co., Ltd. and its approval number is National Medicine Standard H20090158.

[0086] Comparative Example 2

[0087] The Chinese patent medicine Huoxiang Zhengqi Capsule is produced by Tianjin Pharmaceutical Darentang Group Co., Ltd. and its batch number is National Medicine Standard Z10890019.

[0088] Comparative Example 3

[0089] The Chinese medicine composition medicine, the raw materials of which are calculated by weight as follows: Uncaria rhynchophylla, mint, tribulus terrestris, costusroot, chrysanthemum, tuckahoe, magnolia bark and rice sprout.

[0090] The raw materials of the Chinese medicine composition are composed of 3.4 parts of Uncaria rhynchophylla, 6.8 parts of Mentha arvense, 3.4 parts of Tribulus terrestris, 13.6 parts of Aucklandia lappa, 6.8 parts of Chrysanthemum, 27.3 parts of Poria, 13.6 parts of Magnolia officinalis and 10.2 parts of Rice sprouts in parts by weight.

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

[0092] Comparative Example 4

[0093] The Chinese medicine composition medicine, the raw material components by weight are: Angelica dahurica, Guangdong Shenqu, chrysanthemum, patchouli, atractylodes, tangerine peel, trichosanthes, coix seed and kudzu root.

[0094] The raw materials of the Chinese medicine composition are composed of 13.6 parts of Angelica dahurica, 13.6 parts of Guangdong Shenqu, 6.8 parts of Chrysanthemum, 13.6 parts of Patchouli, 13.6 parts of Atractylodes, 6.8 parts of Citrus aurantium, 10.2 parts of Radix Trichosanthis, 17.1 parts of Coix seeds and 13.6 parts of Pueraria.

[0095] The preparation method of the drug is the same as the preparation method 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 established. Different concentrations of Baoji oral liquid extract and positive control drugs Mosapride and Huoxiang Zhengqi capsules were given by gavage. The weight changes and food intake of mice were observed, and the gastric emptying rate, intestinal propulsion rate, and expression levels of serum and tissue biochemical indexes of mice were measured to investigate the effect of the Baoji oral liquid composition on the functional dyspepsia model in young mice.

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

[0099] 1. Experimental Materials

[0100] 1.1 Experimental animals

[0101] 3-4 week old male ICR mice, weighing 12-15g, license number: SCXK (Guangdong) 2022-0002. After the mice were purchased, the animals were fed freely and were adaptively raised for three days at a temperature of 25±0.5℃, relative humidity of 55±5%, and alternating light conditions (12h light-dark cycle). During this study, the experiments were conducted in strict accordance with the requirements of experimental animal protection and ethics. Approved by the Experimental Animal Welfare Ethics Committee (No.: 20231226007).

[0102] 1.2 Experimental Reagents

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

[0104] Table 1 Main experimental reagents for pharmacological effects on the mouse functional dyspepsia model

[0105]

[0106]

[0107] 1.3 Experimental instruments

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

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

[0110]

[0111] 2. Experimental methods

[0112] 2.1 Preparation of drug solution

[0113] The dose of cisplatin was 2 mg / kg. 2 mg was accurately weighed and added to 1 mL of normal saline to prepare a 2 mg / mL stock solution. The solution was then diluted to 0.2 mg / mL with normal saline and administered intragastrically at a dose of 0.1 mL / 10 g.

[0114] The dosage of Mosapride Citrate Tablets is 20 mg / kg. Accurately weigh 20 mg of Mosapride, add 1 mL of normal saline to make a 20 mg / mL stock solution, then dilute it to 2 mg / mL with normal saline, and gavage once at a dose of 0.1 mL / 10 g.

[0115] The specification of Huoxiang Zhengqi Capsule is 0.45g per capsule, and the dosage is oral, 2-4 capsules at a time, 1-2 times a day. According to modern pharmacology research and routine clinical dosage, the clinical dosage of Huoxiang Zhengqi Capsule 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 and converted according to the body surface area conversion coefficient of humans and mice, that is, 0.029g / kg × 9.1 = 0.264g / kg. When preparing, accurately weigh 0.45g of the contents of Huoxiang Zhengqi Capsule and add

[0116] 1.7 mL of normal saline was used to prepare a 264 mg / mL stock solution, which was then diluted to 26.4 mg / mL with normal saline and administered intragastrically 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 decoction pieces, and the dosage is oral, 10mL at a time, 3 times a day. According to modern pharmacological research and clinical routine dosage, the clinical dosage of Baoji oral liquid extract is 0.187g / mL×10mL×3 times / 70kg=0.08g / kg. According to the body surface area conversion coefficient of humans and mice, 0.08g / kg×9.1=0.728g / kg / d. In order to explore the optimal dose of Baoji oral liquid extract for the treatment of functional dyspepsia in mice and observe whether its pharmacological effect is dose-dependent, this experiment used the clinical equivalent dose of Baoji oral liquid extract as a reference to set up a low-dose group of Baoji oral liquid extract (0.365g crude drug / kg / d), a medium-dose group of Baoji oral liquid extract (0.73g crude drug / kg / d), and a high-dose group of Baoji oral liquid extract (1.46g crude drug / kg / d).

[0118] Baoji oral liquid extract high-dose group: accurately measure 1mL of Baoji extract (density 1.2g / mL, crude drug content 4.8g / mL), add 3.3mL of normal saline to make a 1.46g / mL solution, and then dilute with normal saline to 146mg / mL; Baoji oral liquid extract medium-dose group: take 50mL of high-dose group solution, add 50mL of normal saline to make a 73mg / mL solution; Baoji oral liquid extract low-dose group: take the medium-dose group solution and dilute it in half to make a 36.5mg / mL solution. The above different doses of liquid were gavaged once at a dose of 0.1mL / 10g.

[0119] The solvent for preparing the medicine solution is physiological saline, which should be prepared before use and stored temporarily at 4°C for future use.

[0120] 2.2 Animal grouping, medication and sampling

[0121] 2.2.1 Animal grouping and drug intervention

[0122] The mice were weighed and then separated into cages for three days of adaptive feeding. They were randomly divided into 11 groups, 8 mice in each group. The specific groups were as follows: normal group, model group, positive control Mosapride Citrate Tablets (Comparative Example 1) group, positive control Huoxiang Zhengqi Capsule (Comparative Example 2) group, Baoji Oral Liquid Extract Low-dose Group (Example 1), Baoji Oral Liquid Extract Medium-dose Group (Example 1), Baoji Oral Liquid Extract High-dose Group (Example 1), Example 2 Medium-dose Group, Example 3 Medium-dose Group, Comparative Example 3 Medium-dose Group, Comparative Example 4 Medium-dose Group.

[0123] Except for the normal group, the rest of the groups were injected with cisplatin for 4 days (2 mg / kg / d). The food intake of mice decreased significantly from the third day, indicating that the model was successful. The normal group was injected with an equal volume of saline. All mice were fed with standard feed and had free access to water.

[0124] After 4 days of modeling, starting from the 5th day, the drug administration group was gavaged with different doses of liquid medicine: Mosapride citrate tablets: 20 mg / kg / d; Huoxiang Zhengqi capsules: 264 mg / kg / d; Baoji oral liquid extract low dose group (Example 1): 365 mg crude drug / kg / d; Baoji oral liquid extract medium dose group (Example 1): 730 mg crude drug / kg / d; Baoji oral liquid extract high dose group (Example 1): 1460 mg crude drug / kg / d; Example 2-Example 3 and Comparative Example 3-Comparative Example 4 medium dose group: 730 mg crude drug / kg / d. The control group and the model group were gavaged with an equal volume of physiological saline once a day for five consecutive days. All mice were fed with standard feed and had free access to water. After the last gavage, the mice were fasted for 24 hours and had free access to water.

[0125] 2.2.2 Gastric emptying and intestinal propulsion experiments

[0126] After fasting for 24 hours, mice were given 0.4 mL (g) of semisolid nutrient paste. After 20 minutes, the mice were euthanized and the cardia and pylorus were ligated. The total weight and net weight of the stomach were weighed, the total length of the small intestine and the distance from the front end of the solid paste to the pylorus were recorded, and the gastric emptying rate and intestinal propulsion rate were calculated.

[0127] 2.2.3 Collection of serum and tissue samples

[0128] Eyeballs were removed to collect blood, and mouse blood was collected and centrifuged at room temperature for 1 hour (centrifuge parameters: 3000 rpm, 10 min), and the upper serum was separated and stored in a -80°C refrigerator for later use. Mouse stomach tissue was cut and placed in a cryopreservation tube, and frozen in a -80°C refrigerator for later use.

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

[0130] The gastric antrum tissues of the mice in each group were cut out from the same position, fixed with 4% paraformaldehyde, and made into paraffin sections. The sections were stained with hematoxylin and eosin and the histopathological conditions of the gastric antrum were observed under a microscope (×100).

[0131] 2.4 Detection of biochemical index levels in mouse serum and tissues

[0132] Using enzyme-linked immunosorbent assay, reconstitute the serum and tissue samples stored in "2.2.3 Collection of serum and tissue samples", take the kit out of the refrigerator in advance, and wait for the temperature to equilibrate to room temperature. According to the instructions of the kit, detect 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.

[0133] 3. Experimental results

[0134] 3.1 Effects on functional dyspepsia in young mice

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

[0136] like Figure 2 As shown in Table 3, during the modeling period (2-4 days), the weight gain of mice in the model group was slow. From the 3rd day, the weight of mice in the model group was significantly reduced compared with that in the normal group (p < 0.05). From the 5th to the 9th day of the experiment, the weight of mice in the model group resumed growth, and there was a very significant difference in the weight of mice in the model group compared with that in the normal group (p < 0.001).

[0137] During the administration period (5th to 9th day of the experiment), the weight of mice in the Mosapride Citrate Tablets group and the low, medium and high dose groups of Baoji Oral Extract recovered faster. The weight of mice in the model group was significantly different from that in the normal group (p < 0.001); during the administration period (5th to 9th day of the experiment), the weight of mice in the Mosapride Citrate Tablets group and the low, medium and high dose groups of Baoji Oral Extract recovered faster, and the weight of the above groups was statistically different from that of the model group every day from the 6th day (p < 0.05). The weight of mice in the Huoxiang Zhengqi Capsule group recovered slowly, and there was no statistical difference in weight between this group and the model group.

[0138] Table 3 Mouse weight statistics

[0139]

[0140] Figure 2 and 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 tablets group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Baoji oral liquid extract low-dose group (Example 1); BJM: Baoji oral liquid extract medium-dose group (Example 1); BJH: Baoji oral liquid extract high-dose group (Example 1).

[0142] Compared with the model group, the body weight of mice in the Mosa group on the 6th, 7th, 8th and 9th days was significantly different (p < 0.01, p < 0.05). Compared with the model group, the body weight of mice in the BJL group on the 6th, 7th and 8th days was significantly different (p < 0.05). Compared with the model group, the body weight of mice in the BJM group on the 6th, 7th, 8th and 9th days was significantly different (p < 0.05). Compared with the model group, the body weight of mice in the BJH group on the 6th, 7th, 8th and 9th days was significantly different (p < 0.01, p < 0.05).

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

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

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

[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 extremely significantly reduced (p < 0.001). Compared with the model group, the gastric emptying rate of mice in the mosapride citrate tablets group was extremely significantly increased (p < 0.001); the gastric emptying rates of mice in the Huoxiang Zhengqi capsule group, the low, medium and high dose groups of Baoji oral liquid extract, and the Example 2 and Example 3 groups were significantly improved (p < 0.01); there was no statistical difference in the gastric emptying rates 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 tablets group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Baoji oral liquid extract low-dose group (Example 1); BJM: Baoji oral liquid extract medium-dose group (Example 1); BJH: Baoji oral liquid extract high-dose group (Example 1); S2: Example 2 medium-dose group; S3: Example 3 medium-dose group; D3: Comparative Example 3 medium-dose group; D4: Comparative Example 4 medium-dose group.

[0150] 3.1.4 Effects 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 tablets, Huoxiangzhengqi capsule group, Baoji oral liquid extract medium dose group, Example 2 group and Example 3 group was significantly increased (p < 0.05); the intestinal propulsion rate of mice in the Baoji oral liquid extract high dose group was extremely significantly increased (p < 0.001); there was no statistical difference in the intestinal propulsion rate of mice in the Baoji oral liquid extract low dose group, comparative example 3 group and 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 tablets group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Baoji oral liquid extract low-dose group (Example 1); BJM: Baoji oral liquid extract medium-dose group (Example 1); BJH: Baoji oral liquid extract high-dose group (Example 1); S2: Example 2 medium-dose group; S3: Example 3 medium-dose group; D3: Comparative Example 3 medium-dose group; D4: Comparative Example 4 medium-dose group.

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

[0155] like Figure 6 As shown in the figure, the gastric antrum tissue morphology of mice in the normal group was normal, the mucosal layer and muscle layer were clear, the glands were arranged tightly and orderly, and no inflammatory cells or obvious organic changes were observed. In the model group, inflammatory cell infiltration was observed in the gastric antrum mucosal layer of mice, the submucosal layer and the lamina propria were obviously edematous, and the connective tissue was loosely arranged. Only a small amount of inflammatory cell infiltration was observed in the gastric antrum mucosal layer of mice in the drug-treated groups, and no other obvious pathological damage was observed.

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

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

[0158] In order to clarify the effect of the composition of the Baoji oral liquid on the expression of biomarkers in serum and gastric tissue of young mice with functional dyspepsia, this experiment determined 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 the mice in the model group was extremely significantly reduced (p<0.001); compared with the model group, the expression levels of gastrin in the serum of the mice in the mosapride citrate tablets group, the low-, medium- and high-dose groups of Baoji oral liquid extract, and the Example 2 and Example 3 groups were significantly increased (p<0.01, p<0.05); there was no statistical difference in the expression levels of gastrin in the serum of the 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 tablets group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Baoji oral liquid extract low-dose group (Example 1); BJM: Baoji oral liquid extract medium-dose group (Example 1); BJH: Baoji oral liquid extract high-dose group (Example 1); S2: Example 2 medium-dose group; S3: Example 3 medium-dose group; D3: Comparative Example 3 medium-dose group; D4: Comparative Example 4 medium-dose group.

[0163] 3.3.2 Motilin (MTL)

[0164] like Figure 8 As shown, compared with the normal group, the expression level of motilin in the serum of the model group mice was extremely significantly reduced (p<0.001); compared with the model group, the expression levels of motilin in the mice in the mosapride citrate tablets group, 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 expression levels of motilin in the mice in Example 2 and Example 3 groups were significantly increased (p<0.01); there was no statistical difference in the expression levels of motilin in the 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 tablets group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Baoji oral liquid extract low-dose group (Example 1); BJM: Baoji oral liquid extract medium-dose group (Example 1); BJH: Baoji oral liquid extract high-dose group (Example 1); S2: Example 2 medium-dose group; S3: Example 3 medium-dose group; D3: Comparative Example 3 medium-dose group; D4: Comparative Example 4 medium-dose group.

[0167] 3.3.3 Interleukin 4 (IL-4)

[0168] like Fig. 9 As shown, compared with the normal group, the expression level of IL-4 in the gastric tissue of the mice in the model group was significantly decreased (p<0.01); compared with the model group, the expression level of IL-4 in the gastric tissue of the mice in the Huoxiang Zhengqi capsule group and the low-dose Baoji oral liquid extract group was significantly increased (p<0.05), and the expression level of IL-4 in the gastric tissue of the mice in the medium-dose Baoji oral liquid extract group was extremely significantly increased (p<0.001); the expression level of IL-4 in the gastric tissue of the mice in the medium-high-dose Baoji oral liquid extract group, Example 2 group and Example 3 group was significantly increased (p<0.01); the expression level of IL-4 in the gastric tissue of the mice in the comparison example 3 group and the comparison example 4 group was significantly increased (p<0.05).

[0169] Fig. 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 tablets group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Baoji oral liquid extract low-dose group (Example 1); BJM: Baoji oral liquid extract medium-dose group (Example 1); BJH: Baoji oral liquid extract high-dose group (Example 1); S2: Example 2 medium-dose group; S3: Example 3 medium-dose group; D3: Comparative Example 3 medium-dose group; D4: Comparative Example 4 medium-dose group.

[0171] 3.3.4 Interleukin (IL-1β)

[0172] like Fig.10As shown, compared with the normal group, the expression level of interleukin 1β in the gastric tissue of the model group mice was extremely significantly increased (p<0.001); compared with the model group, the expression level of interleukin 1β in the mosapride citrate tablets group was significantly reduced (p<0.01). The expression level of interleukin 1β in the gastric tissue of the mice in the low, medium and high dose groups of Baoji oral liquid extract, Example 2 and Example 3 groups showed a downward trend, 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 gastric tissue of the mice in the Huoxiang Zhengqi capsule group, Comparative Example 3 group and Comparative Example 4 group.

[0173] Fig.10 middle, ### 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 tablets group (Comparative Example 1); HX: Huoxiang Zhengqi capsule group (Comparative Example 2); BJL: Baoji oral liquid extract low-dose group (Example 1); BJM: Baoji oral liquid extract medium-dose group (Example 1); BJH: Baoji oral liquid extract high-dose group (Example 1); S2: Example 2 medium-dose group; S3: Example 3 medium-dose group; D3: Comparative Example 3 medium-dose group; D4: Comparative Example 4 medium-dose group.

[0175] Experiment 2: Loperamide-induced functional dyspepsia in ICR mice

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

[0177] 1. Experimental Materials

[0178] 1.1 Experimental animals

[0179] 3-4 week old male ICR mice, weighing 12-15 g, license number: SCXK (Guangdong) 2022-0002. The animals were fed ad libitum and were adapted to living for three days at a temperature of 25 ± 0.5 °C, relative humidity of 55 ± 5%, and alternating light conditions (12 h light-dark cycle). During this study, the experiments were conducted in strict accordance with the requirements of experimental animal protection and ethics.

[0180] 1.2 Experimental Reagents

[0181] The same experiment as experiment 1 was conducted with cisplatin to induce functional dyspepsia in mice.

[0182] 1.3 Experimental instruments

[0183] The same experiment as experiment 1 was conducted with cisplatin to induce functional dyspepsia in mice.

[0184] 2. Experimental methods

[0185] 2.1 Preparation of drug solution

[0186] The same experiment as experiment 1 was conducted with cisplatin to induce functional dyspepsia in mice.

[0187] 2.2 Animal grouping, medication and sampling

[0188] 2.2.1 Animal grouping and drug intervention

[0189] The mice were quarantined and weighed and then separated into cages for adaptive feeding for 7 days. They were randomly divided into 5 groups, 8 mice in each group. The specific groups were as follows: normal group, model group, positive control mosapride citrate tablets (Comparative Example 1) group, Baoji oral liquid extract medium dose group (Example 1), Baoji oral liquid extract high dose group (Example 1).

[0190] On days 1-7, mice in the normal group were gavaged with 0.2 mL of sterile saline daily, and mice in other groups were gavaged with loperamide (10 mg / kg, 0.2 mL) to construct a functional dyspepsia mouse model. On days 8-12, the normal group was gavaged with 0.2 mL of sterile saline, and the other groups were gavaged with loperamide (10 mg / kg, 0.2 mL). One hour after gavage, the positive control group was gavaged with 20 mg / kg / d of mosapride citrate tablets, the model group was gavaged with 0.2 mL of sterile saline, the medium-dose group of Baoji Oral Liquid Extract was gavaged with 730 mg of crude drug / kg / d of Baoji Oral Liquid Extract in Example 1, and the high-dose group of Baoji Oral Liquid Extract was gavaged with 1460 mg of crude drug / kg / d of Baoji Oral Liquid Extract in Example 1. After gavage with the corresponding drugs on day 21, gastric emptying rate, intestinal propulsion rate, serum and tissue biochemical index levels were detected.

[0191] 2.2.2 Gastric emptying and intestinal propulsion experiments

[0192] The same experiment as experiment 1 was conducted with cisplatin to induce functional dyspepsia in mice.

[0193] 2.2.3 Collection of serum and tissue samples

[0194] The same experiment as experiment 1 was conducted with cisplatin to induce functional dyspepsia in mice.

[0195] 2.3 Detection of biochemical indexes in mouse serum and tissues

[0196] The same experiment as experiment 1 was conducted with cisplatin to induce 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 Fig.11 As shown in the figure, compared with the normal group, the gastric emptying rate of mice in the model group was extremely significantly reduced (p < 0.001). Compared with the model group, the gastric emptying rate of mice in the mosapride citrate tablets group was significantly increased (p < 0.01); the gastric emptying rate of the Baoji oral liquid extract medium and high dose groups did not increase significantly.

[0201] Fig.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 tablets group (Comparative Example 1); BJM: Baoji oral liquid extract medium dose group (Example 1); BJH: Baoji oral liquid extract high dose group (Example 1).

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

[0204] like Fig.12 As shown in the figure, compared with the normal group, the intestinal propulsion rate of mice in the model group was extremely 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), and the gastric emptying rate of mice in the medium and high dose groups of Baoji Oral Liquid Extract was not significantly increased.

[0205] Fig.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 tablets group (Comparative Example 1); BJM: Baoji oral liquid extract medium dose group (Example 1); BJH: Baoji oral liquid extract high dose group (Example 1).

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

[0208] 3.2.1 Gastrin (GAS)

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

[0210] Fig.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 tablets group (Comparative Example 1); BJM: Baoji oral liquid extract medium dose group (Example 1); BJH: Baoji oral liquid extract high dose group (Example 1).

[0212] 3.2.2 Motilin (MTL)

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

[0214] Fig.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 tablets group (Comparative Example 1); BJM: Baoji oral liquid extract medium dose group (Example 1); BJH: Baoji oral liquid extract high dose group (Example 1).

[0216] 3.2.3 Interleukin 4 (IL-4)

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

[0218] Fig.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 tablets group (Comparative Example 1); BJM: Baoji oral liquid extract medium dose group (Example 1); BJH: Baoji oral liquid extract high dose group (Example 1).

[0220] 3.2.4 Interleukin (IL-1β)

[0221] like Fig.16 As shown, compared with the normal group, the expression level of interleukin-1β in 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 mice in the mosapride citrate tablets group was significantly decreased (p<0.01), and the expression level of interleukin-1β in the Baoji oral liquid composition tended to decrease, but there was no significant difference compared with the model group.

[0222] Fig.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 tablets group (Comparative Example 1); BJM: Baoji oral liquid extract medium dose group (Example 1); BJH: Baoji oral liquid extract high dose group (Example 1).

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

[0225] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. Application of Baoji oral liquid composition in the preparation of medicine for treating functional dyspepsia.

2. The use according to claim 1, characterized in that: The treatment of functional dyspepsia includes rapid restoration of body weight and significant improvement in weight gain.

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

4. The use according to claim 1, characterized in that: The treatment of functional dyspepsia includes significantly increasing the gastric emptying rate.

5. The use according to claim 1, characterized in that: The treatment of functional dyspepsia includes significantly increasing the intestinal propulsion rate.

6. The use according to claim 1, characterized in that: The treatment of functional dyspepsia includes protecting gastric mucosa, reducing inflammatory cell infiltration, and repairing the mucosal layer and the muscular layer.

7. The use according to claim 1, characterized in that: The treatment of functional dyspepsia includes significantly increasing the expression of gastrin and motilin in serum.

8. The use according to claim 1, characterized in that: The functional dyspepsia treatment comprises significantly increasing the expression level of IL-4 and reducing the expression level of IL-1β in gastric tissue.

9. The use according to claim 1, characterized in that: The treatment of functional dyspepsia includes the treatment of functional dyspepsia induced by cisplatin.

10. The use according to claim 1, characterized in that: The medicine includes the components in the Baoji oral liquid composition, or can be administered in combination with one or more other therapeutic agents; the components in the Baoji oral liquid composition include: Uncaria rhynchophylla, mint, tribulus terrestris, angelica dahurica, costus root, Guangdong Shenqu, chrysanthemum, patchouli, atractylodes, tuckahoe, magnolia bark, tangerine peel, radix trichosanthis, coix seed, kudzu root and rice sprouts.

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