A pharmaceutical composition for functional dyspepsia, and a preparation method and application thereof

Abstract

The application provides a pharmaceutical composition for functional dyspepsia and a preparation method and application thereof, and belongs to the technical field of medicines, and the pharmaceutical composition comprises the following components: Aucklandia, Atractylodes, Mentha, Agastache, Citrus aurantium, Uncaria, Tribulus terrestris, Guangdong Shenqu, Chrysanthemum, Poria cocos, Radix Trichosanthis, Coix seed, Magnolol, Imperatorin, Isoimperatorin, Oxypeucedanin, Ferulic acid, Vanillic acid, p-Coumaric acid and Puerarin. The pharmaceutical composition comprises traditional Chinese medicine components and compounds, the components interact with each other, the effect of the pharmaceutical composition on improving functional dyspepsia can be improved, and meanwhile, the pharmaceutical composition has excellent stability.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology and relates to a pharmaceutical composition for functional dyspepsia, and in particular to a pharmaceutical composition for functional dyspepsia and a preparation method and application thereof. Background Art

[0002] Functional dyspepsia (FD) is one of the most common functional gastrointestinal diseases in clinical practice. Its main symptoms include upper abdominal pain, upper abdominal distension, early satiety, belching, loss of appetite, nausea, vomiting, etc. It is a group of clinical syndromes after excluding organic diseases.

[0003] The pathogenesis of functional dyspepsia remains unclear. Studies have shown that factors such as impaired gastric fundus relaxation after eating, antral and duodenal motility coordination disorders, visceral hypersensitivity, gastric acid irritation, altered gastrointestinal motility rhythms, psychological and psychiatric stress, poor dietary habits, Helicobacter pylori infection, and genetics are associated with FD. Therefore, the selection of therapeutic agents and combination therapy should be individualized. When using combination therapy, drug interactions should be considered to avoid adverse reactions or compromised efficacy.

[0004] The drugs currently used to treat FD are mainly divided into the following categories:

[0005] (1) Prokinetic drugs: Prokinetic drugs can help relieve meal-related upper abdominal symptoms such as upper abdominal distension and early satiety in patients with FD. They can be used as the first choice for empirical treatment of FD, especially postprandial distress syndrome (PDS). The most commonly used prokinetic drugs in China are mosapride and itopride.

[0006] (2) Acid suppressants: Acid suppressants are mainly divided into two categories, namely H2 receptor antagonists (H2RA) and proton pump inhibitors (PPIs), which can be used as empirical treatment for FD, especially epigastric pain syndrome (EPS), such as ranitidine, famotidine, omeprazole and rabeprazole.

[0007] (3) Digestive enzymes: Digestive enzymes can be used as an auxiliary medicine to treat indigestion, improving symptoms such as abdominal distension and loss of appetite related to meals, such as compound digestive enzyme capsules.

[0008] (4) Drugs for eradicating Helicobacter pylori: For patients with FD infected with Helicobacter pylori, eradication of Helicobacter pylori can improve the symptoms of FD and reduce the risk of peptic ulcer, gastric cancer and gastric lymphoma, such as amoxicillin, clarithromycin and other drugs.

[0009] (5) Anti-anxiety and anti-depressant drugs: For patients with FD caused by psychological and mental adverse stress, anti-depressant and anxiolytic drugs play a certain role in the treatment of FD.

[0010] As can be seen, the optimal treatment for FD varies depending on the cause. Due to FD's high recurrence rate, its primary prevalence in young children, and its difficulty in curing, long-term use of Western medications can easily lead to drug resistance and significant side effects. Therefore, Traditional Chinese Medicine (TCM) has demonstrated unique advantages and is increasingly being used in the treatment of FD. However, these treatments often suffer from issues such as slow efficacy, unclear active ingredients, and high dosages.

[0011] The invention patent with publication number CN105232609A discloses a Chinese medicine composition for treating functional dyspepsia, which is prepared from the following raw materials in parts by weight: 15-25 parts of chicken gizzard lining, 15-25 parts of white atractylodes, 10-20 parts of codonopsis pilosula, 10-25 parts of loofah, 10-15 parts of magnolia bark, 10-15 parts of yanhusuo, 10-15 parts of citron, 10-15 parts of radish seeds, The Chinese medicine composition comprises 5-10 parts of chrysanthemum, 10-25 parts of bamboo leaves, 10-25 parts of pulsatilla, 10-30 parts of notoginseng, 10-20 parts of scutellaria, 10-30 parts of cinnamon bark, 10-30 parts of uncaria, 5-10 parts of polygala, 5-10 parts of lobelia, 5-10 parts of patrinia herb, 5-10 parts of ginger, 15-30 parts of sterculia lychnophora, 15-30 parts of toosendan fruits, and 5-15 parts of gentiana. The Chinese medicine composition has the effects of invigorating the spleen and stomach, digesting food and eliminating stagnation, regulating qi and relieving pain, and tonifying the middle and replenishing qi. It is used to treat functional dyspepsia, has no toxic side effects, and has good therapeutic effect. However, the Chinese medicine composition is used to treat dyspepsia in adults and is not easy to preserve.

[0012] Patent publication number CN106540162A discloses a drug for treating chronic dyspepsia. The drug's ingredients include: Atractylodes macrocephala, Poria cocos, Atractylodes lancea, Magnolia officinalis, Tangerine peel, Cyperus rotundus, Panax ginseng, Cardamomum villosum, Aucklandia lappa, Amomum villosum, Licorice root, and Jujube. The drug is prepared and taken once daily, warm. Ginseng can be decocted separately and taken simultaneously, with Cyperus rotundus added to the decocted later. This drug addresses the problems of existing drugs for treating chronic dyspepsia, such as significant side effects, long duration of use, high relapse rates after discontinuation, and inability to cure the disease. While suitable for treating chronic dyspepsia, it suffers from a prolonged duration of efficacy, requiring more than 10 days to manifest, and poor long-term storage.

[0013] A journal article (Zhang Qunxiao, Observation on the efficacy of Baoji Pills in treating 60 cases of functional dyspepsia. 2005) disclosed a Baoji Pill composed of 16 Chinese herbal medicines: Uncaria rhynchophylla, chrysanthemum, Magnolia officinalis, Atractylodes macrocephala, Patchouli grandiflora, Poria cocos, Citrus aurantium, Angelica dahurica, Coix seed, Malus domestica, Aucklandia lappa, Trichosanthes root, Guangdong Shenqu, Pueraria root, and Menthol. It was used to treat 73 patients with clinical manifestations of postprandial abdominal distension and belching, 85 patients with anorexia, nausea, vomiting, and regurgitation, and 55 patients with heartburn and retrosternal pain. After 10 courses of treatment, the total effective rate was 91.7%, and the efficacy lasted for a long time. Moreover, the cause of the disease in patients with FD was not distinguished.

[0014] Due to the above shortcomings, it is urgent to develop a pharmaceutical composition with better efficacy and high stability that can be used for functional dyspepsia. Therefore, the present invention provides a pharmaceutical composition for functional dyspepsia. Summary of the Invention

[0015] The present invention addresses the problems of the prior art and provides a pharmaceutical composition for functional dyspepsia, its preparation method, and its use. The pharmaceutical composition comprises traditional Chinese medicine components and compounds, and the interactions between the components enhance the effectiveness of the pharmaceutical composition in improving functional dyspepsia. Furthermore, the pharmaceutical composition exhibits excellent stability, and the active ingredients exhibit high stability.

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

[0017] In a first aspect, the present invention provides a pharmaceutical composition for functional dyspepsia, comprising: costus root, atractylodes lancea, mint, patchouli, tangerine peel, Uncaria rhynchophylla, Tribulus terrestris, Guangdong Shenqu, chrysanthemum, Poria cocos, radix trichosanthis, coix seed, magnolol, imperatorin, isoimperatorin, oxidized imperatorin, ferulic acid, vanillic acid, p-coumaric acid and puerarin.

[0018] Preferably, the pharmaceutical composition comprises the following components in parts by mass: 13.0-14.5 parts of costus root, 13.0-14.5 parts of atractylodes, 5.5-9 parts of mint, 13.0-14.5 parts of patchouli, 6.0-7.8 parts of tangerine peel, 3.0-4.0 parts of Uncaria rhynchophylla, 3.0-4.0 parts of tribulus terrestris, 13.0-14.5 parts of Guangdong Shenqu, 6.0-7.5 parts of chrysanthemum, 2 parts of Poria cocos, 13.0-14.5 parts of chrysanthemum, 6.0-7.5 parts of chrysanthemum, 2 parts of chrysanthemum and 13.0-14.5 parts of chrysanthemum. 5-30 parts, Radix Trichosanthis 9.5-11.0 parts, Semen Coicis 16-18 parts, Magnolia officinalis 0.25-0.40 parts, Imperatorin 0.2-1.1 parts, Isoperibolin 0.2-1.1 parts, Oxidized Imperatorin 0.2-1.1 parts, Ferulic acid 0.01-0.1 parts, Vanillic acid 0.01-0.1 parts, p-Coumaric acid 0.01-0.1 parts and Puerarin 0.1-1.5 parts.

[0019] More preferably, the pharmaceutical composition comprises the following components in parts by mass: 13.2-14.0 parts of costus root, 13.2-14.0 parts of atractylodes, 6.0-7.5 parts of mint, 13.2-14.0 parts of patchouli, 6.0-7.0 parts of tangerine peel, 3.1-3.7 parts of Uncaria rhynchophylla, 3.1-3.7 parts of tribulus terrestris, 13.2-14.0 parts of Guangdong Shenqu, 6.5-7.0 parts of chrysanthemum, 26 parts of tuckahoe, 13.2-14.0 parts of chrysanthemum, 6.5-7.0 parts of tuckahoe, 26 parts of chrysanthemum and 13.2-14.0 parts of chrysanthemum. -28 parts, Radix Trichosanthis 10.0-10.5 parts, Semen Coicis 17.0-17.5 parts, Magnolia officinalis 0.25-0.40 parts, Imperatorin 0.2-1.1 parts, Isoperibolin 0.2-1.1 parts, Oxidized Imperatorin 0.2-1.1 parts, Ferulic acid 0.01-0.1 parts, Vanillic acid 0.01-0.1 parts, p-Coumaric acid 0.01-0.1 parts and Puerarin 0.1-1.5 parts.

[0020] Preferably, the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition is 1-3:1-10:1-3:0.5-5, preferably 1-3:1-6:1-3:0.5-5, more preferably 1-2:1-3:1-2:0.5-5.

[0021] Preferably, in the pharmaceutical composition, the mass ratio of magnolol, atractylodes, patches of galangal and red orange peel is 1-2:30-80:30-80:15-50, preferably 1-2:30-60:30-60:15-30, and more preferably 1:30-60:30-60:15-30.

[0022] Preferably, in the pharmaceutical composition, Patchouli is Patchouli.

[0023] Preferably, the drug may also be used in combination with a pharmaceutically acceptable carrier.

[0024] 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.

[0025] In the present invention, the type and manufacturer of the pharmaceutically acceptable carrier have no significant impact on the technical effect of the drug.

[0026] 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 flavor.

[0027] In one embodiment, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, and the pharmaceutically acceptable carrier is selected from sucrose and polysorbate.

[0028] In a second aspect, the present invention provides a method for preparing the pharmaceutical composition, comprising the following steps:

[0029] 1) distilling costus root, atractylodes lancea, mint, patches of tangerine peel, and red orange peel to collect volatile oil and residual substances, decocting the residual substances in water, concentrating the decoction, adding ethanol, collecting and concentrating the filtrate 1 to obtain an extract 1;

[0030] 2) decoct Uncaria rhynchophylla, Tribulus terrestris, Guangdong Shenqu (Chinese Herbal Medicine) and chrysanthemum in water, concentrate the decoction, add ethanol, collect and concentrate the filtrate 2 to obtain extract 2;

[0031] 3) decocting coix seeds in water, concentrating the decoction, adding ethanol, collecting and concentrating the filtrate 3 to obtain extract 3;

[0032] 4) Decoction of Poria cocos and Radix Trichosanthis was concentrated, ethanol was added, and filtrate 4 was collected and concentrated to obtain extract 4;

[0033] 5) Evenly mix extract 1, extract 2, extract 3, extract 4, magnolol, imperatorin, isoimperatorin, oxyimperatorin, ferulic acid, vanillic acid, p-coumaric acid, and puerarin, then add volatile oil and mix evenly to obtain a pharmaceutical composition.

[0034] The step 1) specifically comprises: distilling costus root, atractylodes lancea, mint, patchouli and red orange peel for 1-3 hours, preferably 2-3 hours; collecting volatile oil and residual substances, decocting the residual substances in water for 1-3 times, with the decoction time of each decoction not limited, preferably 1-3 hours; concentrating the decoction, adding ethanol, and standing for preferably 12-48 hours, then collecting filtrate 1, wherein the volume fraction of ethanol in filtrate 1 is 40-50%, preferably 45-50%; and concentrating filtrate 1 to obtain extract 1.

[0035] The step 2) is specifically as follows: decocting Uncaria rhynchophylla, Tribulus terrestris, Guangdong Shenqu and chrysanthemum in water for 1-3 times, with the decoction time for each time not limited, preferably 1-3 hours; concentrating the decoction, adding ethanol, and standing for preferably 12-48 hours, then collecting filtrate 2, wherein the volume fraction of ethanol in filtrate 2 is 40-60%; and concentrating filtrate 2 to obtain extract 2.

[0036] The step 3) is specifically as follows: decocting the coix seeds in water for 1-3 times, with the decoction time for each time not limited, preferably 1-3 hours; concentrating the decoction, adding ethanol, and allowing the decoction to stand for preferably 12-48 hours, then collecting filtrate 3, wherein the volume fraction of ethanol in filtrate 3 is 40-60%; and concentrating filtrate 3 to obtain extract 3.

[0037] The step 4) is specifically: water decocting the poria cocos and the trichosanthes kirilowii, the number of times of water decocting is 1-3 times, the time of each water decocting is not limited, preferably 1-3 hours; concentrating the decoction, adding ethanol, standing, the standing time is preferably 12-48 hours, then collecting the filtrate 4, the volume fraction of ethanol in the filtrate 4 is 40-60%; concentrating the filtrate 4 to obtain the extract 4.

[0038] The step 5) is specifically: mixing the extract 1, the extract 2, the extract 3, the extract 4, the magnolol, the imperatorin, the isoimperatorin, the oxypeucedanin, the ferulic acid, the vanillic acid, the p-coumaric acid and the puerarin, fully stirring until mixed uniformly, then adding the volatile oil drop by drop while stirring, mixing and stirring uniformly to obtain the pharmaceutical composition. In the stirring process, the temperature of the system is preferably controlled in the range of 25-30 DEG C to avoid the volatile oil volatilizing due to the temperature rising.

[0039] In a third aspect, the present application further provides a use of the pharmaceutical composition prepared by the above technical scheme or the preparation method in the preparation of a drug for treating functional dyspepsia.

[0040] Preferably, in the use, the administration mode of the drug includes oral, sublingual, oral mucosa, intravenous, intramuscular, intraperitoneal, subcutaneous, transdermal, nasal and rectal routes.

[0041] In the present application, in the use, the dosage form of the drug can be solid, liquid or gas.

[0042] The pharmaceutical composition can be prepared into different dosage forms, including but not limited to powder, tablet, granule, pill, hard capsule, soft capsule, cream, ointment, plaster, gel, paste, powder, patch, solution, suspension, injection, syrup, liniment, emulsion, tincture, elixir, aerosol or spray.

[0043] Compared with the prior art, the present application has the following beneficial effects:

[0044] Firstly, the present application uses traditional Chinese medicine components and compounds in combination, the components interact with each other, which can improve the effect of the pharmaceutical composition on functional dyspepsia, and the pharmaceutical composition has excellent stability and high stability of active ingredients.

[0045] Secondly, in the present application, under the condition that the mass ratio of the imperatorin, the isoimperatorin, the oxypeucedanin and the puerarin is 1-3:1-10:1-3:0.5-5, the three coumarin compounds and the puerarin interact with each other, which can improve functional dyspepsia.

[0046] Thirdly, the magnolol in the present invention cooperates with atractylodes, patches of patches and red orange peel in a mass ratio of 1-2:30-80:30-80:15-50 to improve the effect of treating functional dyspepsia. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 This is the flow chart of animal experiments for the cisplatin-induced functional dyspepsia model in mice;

[0048] Figure 2 The weight of mice after five days of drug administration is shown in Table 1. Compared with the normal group, ### P<0.001; compared with the model control group, * P<0.05, ** P < 0.01, *** P < 0.001; compared with the middle dose group (D6) in comparative example 6, + P<0.05, +++ P < 0.001;

[0049] Figure 3 The results of gastric emptying rate of mice after five days of drug administration; compared with the normal group, ### P<0.001; compared with the model control group, * P<0.05, ** P < 0.01, *** P < 0.001; compared with the middle dose group (D6) in comparative example 6, +++ P < 0.001;

[0050] Figure 4 The results of the intestinal propulsion rate of mice after five days of administration; compared with the normal group, ### P<0.001; compared with the model control group, ** P < 0.01, *** P < 0.001; compared with the middle dose group (D6) in comparative example 6, + P<0.05, ++ P < 0.01;

[0051] Figure 5 is the gastrin (GAS) level of mice after five days of administration; compared with the normal group, ### P<0.001; compared with the model control group, * P<0.05, ** P < 0.01, *** P < 0.001; compared with the middle dose group (D6) in comparative example 6, + P<0.05, ++ P < 0.01, +++ P < 0.001;

[0052] Figure 6 is the level of motilin (MTL) in mice after five days of administration; compared with the normal group, ### P<0.001; compared with the model control group, * P<0.05, ** P < 0.01, *** P < 0.001; compared with the middle dose group (D6) in comparative example 6, + P<0.05, ++ P < 0.01, +++ P < 0.001;

[0053] Figure 7 The interleukin-4 (IL-4) level of mice after five days of administration; compared with the normal group, ### P<0.001; compared with the model control group, * P<0.05, ** P < 0.01, *** P < 0.001; compared with the middle dose group (D6) in comparative example 6, + P<0.05, ++ P < 0.01;

[0054] Figure 8 is the interleukin (IL-1β) level of mice after five days of administration; compared with the normal group, ### P<0.001; compared with the model control group, * P<0.05, ** P < 0.01; compared with the middle dose group (D6) in comparative example 6, + P<0.05, ++ P < 0.01;

[0055] Figure 9 The figure shows the loss rate of puerarin in the pharmaceutical composition over 48 months; different letters between a and c indicate significant differences, and the significance level is α=0.05. DETAILED DESCRIPTION

[0056] It is worth noting that, unless otherwise specified, the raw materials used in the present invention are all common commercially available products, and their sources are not specifically limited.

[0057] Magnolia officinalis: purity ≥98% (HPLC), purchased from Maclean, product number M813634;

[0058] Imperatorin: purity ≥98% (HPLC), purchased from Chengdu Gelipu Biotechnology Co., Ltd., product number JOT-10460;

[0059] Isoimperatorin: purity 98%, purchased from FUORAIN / Fuyu, product number NP01139;

[0060] Oxypeucedanum: purity ≥98%, purchased from Topo Biotechnology, product number TOP0067;

[0061] Ferulic acid: purity 98%, purchased from source leaves, product number S30464;

[0062] Vanillic acid: purity 98%, purchased from source leaves, product number S31038;

[0063] p-Coumaric acid: purity 98%, purchased from Le Yan, product number 1033825;

[0064] Puerarin: Purity 98%, purchased from Maclean, product number P816259.

[0065] Examples 1-8 and Comparative Examples 1-6

[0066] The pharmaceutical composition was prepared according to the formula in Table 1.

[0067] Table 1 Pharmaceutical composition formula of Examples 1-8 and Comparative Examples 1-6

[0068]

[0069]

[0070] The preparation steps of the pharmaceutical compositions of Examples 1-8 are as follows:

[0071] 1) steam distilling costus root, atractylodes lancea, mint, patches of galangal, and red orange peel for 2 hours, collecting volatile oil and residual material, decocting the residual material twice for 2 hours each time, filtering and combining the two decoctions, and concentrating the decoction to a relative density of 1.08-1.12 (60° C.), cooling, adding ethanol to an alcohol content (volume fraction of ethanol) of 45%, and standing overnight. The filtrate was collected and concentrated to obtain extract 1;

[0072] 2) Decoction of Uncaria rhynchophylla, Tribulus terrestris, Guangdong Shenqu (Chinese Herbal Medicine) and chrysanthemum twice for 2 hours each time, filtering and combining the two decoctions, and concentrating the decoction to a relative density of 1.02-1.05 (at 60° C.). Ethanol was added to adjust the alcohol content to 40%, and the filtrate was collected and concentrated to obtain extract 2;

[0073] 3) Decoctioning coix seeds twice, each for 1.5 hours, filtering and combining the two decoctions, and concentrating the decoction to a relative density of 1.02-1.05 (60° C.). Adding ethanol to a concentration of 50% alcohol, collecting and concentrating the filtrate to obtain extract 3;

[0074] 4) Poria cocos and Radix Trichosanthis were subjected to 2 times of water decoction, each for 2 hours, the decoction liquid of the two times was filtered and combined, and then the decoction liquid was concentrated to a relative density of 1.02-1.05 (60°C), cooled, ethanol was added to make the alcohol content 60%, the filtrate was collected and concentrated to obtain extract 4;

[0075] 5) The extract 1, the extract 2, the extract 3, the extract 4, magnolol, imperatorin, isoimperatorin, oxypeucedanin, ferulic acid, vanillic acid, p-coumaric acid and puerarin were mixed at room temperature, fully stirred until mixed uniformly, then the volatile oil was added dropwise while stirring, mixed uniformly to obtain a pharmaceutical composition with a relative density of 1.3 (25°C), and the obtained pharmaceutical composition was stored in a sealed manner.

[0076] The difference between Comparative Example 1 and Example 1 is that “ferulic acid 0.04 g, vanillic acid 0.08 g, p-coumaric acid 0.04 g” is replaced by “ferulic acid 0.16 g”, and the others are the same as Example 1 to prepare a pharmaceutical composition.

[0077] The difference between Comparative Example 2 and Example 1 is that “ferulic acid 0.04 g, vanillic acid 0.08 g, p-coumaric acid 0.04 g” is replaced by “ferulic acid 0.12 g, p-coumaric acid 0.04 g”, and the others are the same as Example 1 to prepare a pharmaceutical composition.

[0078] The difference between Comparative Example 3 and Example 1 is that “imperatorin 0.3 g, isoimperatorin 0.9 g and oxypeucedanin 0.3 g” is replaced by “imperatorin 1.1 g, oxypeucedanin 0.4 g”, and the others are the same as Example 1 to prepare a pharmaceutical composition.

[0079] The difference between Comparative Example 4 and Example 1 is that “imperatorin 0.3 g, isoimperatorin 0.9 g, oxypeucedanin 0.3 g and puerarin 1.5 g” is replaced by “imperatorin 1.2 g, isoimperatorin 0.1 g, oxypeucedanin 0.1 g and puerarin 1.6 g”, and the others are the same as Example 1 to prepare a pharmaceutical composition.

[0080] The difference between Comparative Example 5 and Example 1 is that “magnolol 0.3 g, rhizoma atractylodis 13.6 g, pachystachys uribescens 13.6 g, fructus aurantii 6.8 g” is replaced by “magnolol 2.3 g, rhizoma atractylodis 11 g, pachystachys uribescens 16 g, fructus aurantii 5 g”, and the others are the same as Example 1 to prepare a pharmaceutical composition.

[0081] The difference between Comparative Example 6 and Example 1 is that "magnolia bark 0.3g, imperatorin 0.3g, isoimperatorin 0.9g, oxidized imperatorin 0.3g, ferulic acid 0.04g, vanillic acid 0.08g, p-coumaric acid 0.04g and puerarin 1.5g" are replaced with "Magnolia bark 15g, Angelica dahurica 15g, rice sprout 10g, Pueraria root 15g"; the preparation steps of the pharmaceutical composition are as follows:

[0082] 1) steam distilling costus root, atractylodes lancea, mint, patches of galangal, and red orange peel for 2 hours, collecting volatile oil and residual material, decocting the residual material twice for 2 hours each time, filtering and combining the two decoctions, and concentrating the decoction to a relative density of 1.08-1.12 (60° C.), cooling, adding ethanol to a 45% alcohol content, and standing overnight. The filtrate was collected and concentrated to obtain extract 1;

[0083] 2) Decoction of Uncaria rhynchophylla, Tribulus terrestris, Guangdong Shenqu, Chrysanthemum Flos, and Magnolia officinalis was performed twice, each time for 2 hours. The two decoctions were filtered and combined, and then the decoction was concentrated to a relative density of 1.02-1.05 (60° C.). Ethanol was added to adjust the alcohol content to 40%. The filtrate was collected and concentrated to obtain Extract 2;

[0084] 3) decocting coix seeds and rice sprouts twice, each time for 1.5 hours, filtering and combining the two decoctions, and concentrating the decoction to a relative density of 1.02-1.05 (60° C.), adding ethanol to a concentration of 50% alcohol, collecting and concentrating the filtrate to obtain extract 3;

[0085] 4) Decoct Poria cocos, Radix Trichosanthis, Angelica dahurica, and Radix Puerariae twice for 2 hours each time. Filter and combine the two decoctions, then concentrate the decoction to a relative density of 1.02-1.05 (60°C). Cool, add ethanol to a concentration of 60% alcohol, and collect the filtrate and concentrate to obtain Extract 4.

[0086] 5) At room temperature, extract 1, extract 2, extract 3, and extract 4 are mixed and stirred thoroughly until the mixture is uniformly mixed. Then, volatile oil is added dropwise while stirring and mixed uniformly to obtain a pharmaceutical composition with a relative density of 1.3 (25° C.). The obtained pharmaceutical composition is sealed and stored.

[0087] Test Example 1

[0088] Cisplatin-induced functional dyspepsia experiment in mice

[0089] A functional dyspepsia model in mice was induced by cisplatin. The drug composition of different concentrations was administered by gavage. The changes in mouse body weight were observed, and the gastric emptying rate, small intestinal propulsion rate, and expression levels of mouse serum and tissue biochemical indicators were measured to investigate the effect of the drug composition on the functional dyspepsia model in young mice.

[0090] 1. Experimental Materials

[0091] 1.1 Experimental Animals

[0092] 3-4 week old male ICR mice weighing 13-15 g were purchased (Experimental Animal License Number: SCXK(粤)2022-0002). After purchase, the mice were housed ad libitum for three days at a temperature of 25±0.5°C, a relative humidity of 55±5%, and alternating light conditions (12-h light-dark cycle). During this study, all experiments were conducted in strict accordance with the requirements of laboratory animal care and ethical standards. The animal experimental protocol was approved by the Laboratory Animal Welfare and Ethics Committee (No.: 20231226007).

[0093] 1.2 Experimental Reagents

[0094] The main experimental reagents for the pharmacological effects on the mouse functional dyspepsia model are shown in Table 2.

[0095] Table 2 Main experimental reagents for pharmacological effects on the functional dyspepsia model in mice

[0096]

[0097]

[0098] 1.3 Experimental instruments

[0099] The main experimental instruments for the pharmacological effects on the functional dyspepsia model in mice are shown in Table 3.

[0100] Table 3 Main experimental instruments for the pharmacological effects on the functional dyspepsia model in mice

[0101]

[0102] 2. Experimental methods

[0103] 2.1 Preparation of drug solution

[0104] The dose of cisplatin is 2 mg / kg. Accurately weigh 2 mg and add 1 mL of normal saline to prepare a 2 mg / mL stock solution. Then dilute it with normal saline to 0.2 mg / mL and administer it by gavage once at a dose of 0.1 mL / 10 g.

[0105] The dosage of mosapride citrate tablets is 20 mg / kg. Accurately weigh 20 mg of mosapride and add 1 mL of normal saline to prepare a 20 mg / mL stock solution. Then dilute it with normal saline to 2 mg / mL and administer a single oral dose of 0.1 mL / 10 g.

[0106] The specification of the pharmaceutical composition is that each 1mL is equivalent to 0.187g of the decoction piece, and the dosage is oral, 10mL at a time, 3 times a day. According to modern pharmacological research and routine clinical dosage, the clinical dosage of the pharmaceutical composition is 0.187g / mL×10mL×3 times / 70kg=0.08g / kg. According to the body surface area conversion coefficient of humans and mice, that is, 0.08g / kg×9.1=0.728g / kg / d. In order to explore the optimal dose of the pharmaceutical composition for treating the functional dyspepsia model in mice and observe whether its pharmacological effect is dose-dependent, this experiment set up a low-dose group (0.365g / d), a medium-dose group (0.73g / d), and a high-dose group (1.46g / d) of the pharmaceutical composition with the clinical equivalent dose of the pharmaceutical composition as a reference.

[0107] High-dose group: Accurately measure 730 mg of the drug composition and add 5 mL of normal saline to a final solution of 146 mg / mL. Medium-dose group: Dilute the high-dose group solution in half to a final solution of 73 mg / mL. Low-dose group: Dilute the medium-dose group solution in half to a final solution of 36.5 mg / mL. Administer each of the above different doses of the drug solution by single oral gavage at a dose of 0.1 mL / 10 g.

[0108] Semisolid paste (300 mL) was prepared with 10 g sodium carboxymethylcellulose (CMC-Na), 16 g milk powder, 8 g edible corn starch, 8 g white sugar, 3 g activated carbon, and 2 mL ink, and was administered orally at a dose of 0.4 mL (g) per animal.

[0109] The solvent for preparing the medicine solution is normal saline, which should be prepared before use and stored temporarily at 4°C for future use.

[0110] 2.2 Animal grouping, medication and sampling

[0111] 2.2.1 Animal grouping and drug intervention

[0112] Figure 1 This is the animal experiment flow chart of the cisplatin-induced functional dyspepsia model in mice, specifically:

[0113] Mice were quarantined, weighed, and then caged and adaptively reared for three days. They were randomly divided into 19 groups of 8 mice each. The specific groups were as follows: normal control group (N), model control group (FD), positive control group (mosapride citrate tablets, Mosa), low-dose group (S1-1) of Example 1, medium-dose group (S1-2) of Example 1, high-dose group (S1-3) of Example 1, medium-dose groups (S2-S8) of Examples 2-8, and medium-dose groups (D1-D6) of Comparative Examples 1-6.

[0114] All mice except the normal control group received intraperitoneal injections of cisplatin (2 mg / kg / day) for 4 days. The normal control group received an equal volume of saline. All mice were fed a standard diet and had free access to water.

[0115] Four days after modeling, starting on day 5, the drug-treated groups were gavaged with different doses of the following: positive control group: 20 mg / kg / day of mosapride citrate tablets; low-dose group of Example 1: 365 mg / kg / day; medium-dose group of Example 1: 730 mg / kg / day; high-dose group of Example 1: 1460 mg / kg / day; medium-dose groups of Examples 2-8 and Comparative Examples 1-6: 730 mg / kg / day. The control and model groups were gavaged with an equal volume of normal saline once daily for five consecutive days. All mice were fed a standard diet and had free access to water. After the final gavage, the mice were fasted for 24 hours and had free access to water. The mice were weighed.

[0116] 2.3 Gastric emptying and small intestinal propulsion experiments

[0117] Mice were fasted for 24 hours and then given 0.4 mL (g) of semisolid nutrient paste. Twenty minutes later, the mice were euthanized and the cardia and pylorus were ligated. The total and net weights of the stomach were weighed, and the total length of the small intestine and the distance from the front of the semisolid paste to the pylorus were recorded. Gastric emptying rate and small intestinal propulsion rate were calculated.

[0118] 2.4 Collection of serum and tissue samples

[0119] Blood was collected from the eyeballs and allowed to stand at room temperature for 1 hour before centrifugation (3000 rpm, 10 min). The upper serum layer was separated and stored in a -80°C freezer until further use. Mouse stomach tissue was excised, placed in a cryovial, and stored in a -80°C freezer until further use.

[0120] 2.5 Detection of biochemical index levels in mouse serum and tissues

[0121] Using enzyme-linked immunosorbent assay (ELISA), reconstitute the serum and tissue samples stored in "2.4 Serum and Tissue Sample Collection." Remove the kit from the refrigerator in advance and allow it to equilibrate to room temperature. Following the kit instructions, assay 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.

[0122] 3. Experimental results:

[0123] 3.1 Effects of the pharmaceutical composition on functional dyspepsia in young mice

[0124] 3.1.1 Effect of the drug composition on the body weight of young mice with dyspepsia

[0125] The weight of mice after five days of administration was as follows Figure 2The results are as follows:

[0126] (1) Compared with the normal group, the body weight of mice in the model control group (FD) was significantly reduced ( ### P<0.001).

[0127] The results showed that compared with the normal group, the weight gain of young mice after modeling was significantly slowed down due to indigestion.

[0128] (2) Compared with the model control group, the body weight of mice in the positive control group (Mosa), the low-dose group (S1-1) of Example 1, the medium-dose group (S1-2) of Example 1, the high-dose group (S1-3) of Example 1, the medium-dose group (S2-S8) of Examples 2-8, and the medium-dose group (D1-D6) of Comparative Examples 1-6 were significantly increased ( * P<0.05, ** P < 0.01, *** P < 0.001). Among them, the body weights of mice in the medium-dose groups (D1-D6) of Comparative Examples 1-6 were all lower than those in the medium-dose group (S1-2) of Example 1, the high-dose group (S1-3) of Example 1, and the medium-dose groups (S2-S8) of Examples 2-8.

[0129] The results showed that the pharmaceutical compositions of Examples 1-8 and Comparative Examples 1-6 of the present invention can regulate the body weight of functional dyspepsia model mice and significantly increase the body weight of the mice. Among them, the pharmaceutical composition of Example 1 has a better effect.

[0130] (3) Furthermore, the effects of the pharmaceutical compositions of Comparative Examples 1-6 on the body weight of mice were compared, and it was found that the pharmaceutical composition of Comparative Example 6 was more effective. Therefore, Comparative Example 6 was compared with the compositions of Examples 1-8.

[0131] Compared with the medium dose group (D6) in comparative example 6, the body weight of mice in the medium dose group (S1-2) in example 1, the high dose group (S1-3) in example 1, and the medium dose groups (S2-S8) in examples 2-8 were significantly increased ( + P<0.05, +++ P<0.001).

[0132] The results showed that the body weight of mice in the medium-dose groups of Examples 1-8 and the high-dose group of Example 1 was significantly increased compared to the optimal group in the comparative example (i.e., Comparative Example 6). Therefore, compared to the medium-dose groups (D1-D5) of Comparative Examples 1-5, which were slightly worse than the medium-dose group (D6) of Comparative Example 6, the body weight of mice in the medium-dose group (S1-2) of Example 1 was significantly increased.

[0133] The pharmaceutical compositions of the dose groups (D1-D2) in Comparative Examples 1-2 used one or two of ferulic acid, vanillic acid, and p-coumaric acid. Compared with the dose groups (D1-D2) in Comparative Examples 1-2, the body weight of mice in the dose group (S1-2) in Example 1 was significantly increased. This indicates that the pharmaceutical compositions of the examples using ferulic acid, vanillic acid, and p-coumaric acid interact with other components to significantly increase the body weight of mice.

[0134] The pharmaceutical composition of the dosage group (D3) in Comparative Example 3 uses two of imperatorin, isoimperatorin and oxidized imperatorin. Compared with the dosage group (D3) in Comparative Example 3, the body weight of mice in the dosage group (S1-2) in Example 1 was significantly increased. This shows that the pharmaceutical composition in the example uses imperatorin, isoimperatorin and oxidized imperatorin in combination with other components to significantly increase the body weight of mice.

[0135] Furthermore, compared with the dosage group (D4) in Comparative Example 4, the body weight of mice in the dosage group (S1-2) in Example 1 was significantly increased. This indicates that the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition of the embodiment can more effectively increase the body weight of mice in the range of 1-3:1-10:1-3:0.5-5.

[0136] Compared with the dose group (D5) in Comparative Example 5, the body weight of mice in the dose group (S1-2) in Example 1 was significantly increased. This indicates that the mass ratio of magnolol, atractylodes, patchouli, and tangerine peel in the pharmaceutical composition of the example can be more effectively increased in the range of 1-2:30-80:30-80:15-50.

[0137] In the pharmaceutical composition of the dose group (D6) in Comparative Example 6, magnolol, imperatorin, isoimperatorin, oxidized imperatorin, ferulic acid, vanillic acid, p-coumaric acid, and puerarin were replaced with the traditional Chinese medicine components magnolia bark, angelica dahurica, rice sprout, and kudzu root. Compared with the dose group (D6) in Comparative Example 6, the body weight of mice in the dose group (S1-2) in Example 1 was significantly increased. This shows that the components in the pharmaceutical composition of the example interact with each other and can more effectively increase the body weight of mice.

[0138] The above results show that the components of the pharmaceutical composition of the embodiment interact with each other and can significantly alleviate the slowdown in weight gain caused by indigestion. Furthermore, the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition is in the range of 1-3:1-10:1-3:0.5-5, which can more effectively increase the weight of mice. The mass ratio of magnolol, atractylodes, patchouli and tangerine peel in the pharmaceutical composition is in the range of 1-2:30-80:30-80:15-50, which can also more effectively increase the weight of mice.

[0139] 3.1.2 Effect of the drug composition on gastric emptying rate in young mice with dyspepsia

[0140] The gastric emptying rate of mice after five days of administration is as follows Figure 3 The results are as follows:

[0141] (1) Compared with the normal group, the gastric emptying rate of mice in the model control group (FD) was significantly decreased ( ### P<0.001).

[0142] The results showed that compared with the normal group, the gastric emptying rate of young mice was significantly reduced after modeling.

[0143] (2) Compared with the model control group, the gastric emptying rates of mice in the positive control group (Mosa), the low-dose group of Example 1 (S1-1), the medium-dose group of Example 1 (S1-2), the high-dose group of Example 1 (S1-3), the medium-dose groups of Examples 2-8 (S2-S8), and the medium-dose groups of Comparative Examples 1-6 (D1-D6) were significantly increased ( * P<0.05, ** P < 0.01, *** P < 0.001). Among them, the gastric emptying rates of mice in the medium-dose groups (D1-D6) of Comparative Examples 1-6 were lower than those in the low-dose group (S1-1) of Example 1, the medium-dose group (S1-2) of Example 1, the high-dose group (S1-3) of Example 1, and the medium-dose groups (S2-S8) of Examples 2-8.

[0144] The results showed that the pharmaceutical compositions of Examples 1-8 and Comparative Examples 1-6 of the present invention could alleviate the symptoms of delayed gastric emptying in the model group mice and significantly improve the gastric emptying rate of the mice. Among them, the pharmaceutical composition of Example 1 had the better effect.

[0145] (3) Further, the effects of the pharmaceutical compositions of Comparative Examples 1-6 on the emptying rate of mice were compared, and it was found that the pharmaceutical composition of Comparative Example 6 had a more excellent effect. Therefore, Comparative Example 6 was compared with the compositions of Examples 1-8.

[0146] Compared with the medium dose group (D6) of Comparative Example 6, the gastric emptying rates of mice in the low dose group (S1-1) of Example 1, the medium dose group (S1-2) of Example 1, the high dose group (S1-3) of Example 1, and the medium dose groups (S2-S8) of Examples 2-8 were significantly increased ( +++ P<0.001).

[0147] The results showed that the gastric emptying rate of mice in the medium-dose groups of Examples 1-8, the low-dose group of Example 1, and the high-dose group of Example 1 was significantly improved compared to the optimal group in the comparative example (i.e., Comparative Example 6). Therefore, compared to the medium-dose groups (D1-D5) of Comparative Examples 1-5, which were slightly worse than the medium-dose group (D6) of Comparative Example 6, the gastric emptying rate of mice in the medium-dose group (S1-2) of Example 1 was significantly improved.

[0148] Compared with the medium-dose groups (D1-D2) in Comparative Examples 1-2, the gastric emptying rate of mice in the medium-dose group (S1-2) in Example 1 was significantly improved. This indicates that the pharmaceutical composition of the example, using ferulic acid, vanillic acid, p-coumaric acid and other components, can significantly improve the gastric emptying rate of mice.

[0149] Compared with the dose group (D3) in comparative example 3, the gastric emptying rate of mice in the dose group (S1-2) in Example 1 was significantly improved. This shows that the pharmaceutical composition of the example uses imperatorin, isoimperatorin and oxidized imperatorin, which interact with other components to improve the gastric emptying rate of mice.

[0150] Compared with the dosage group (D4) in comparative example 4, the gastric emptying rate of mice in the dosage group (S1-2) in example 1 was significantly improved, which indicates that the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition of the example can more effectively improve the gastric emptying rate of mice in the range of 1-3:1-10:1-3:0.5-5.

[0151] Compared with the dose group (D5) in comparative example 5, the gastric emptying rate of mice in the dose group (S1-2) in Example 1 was significantly improved, which indicates that the mass ratio of magnolia officinalis, atractylodes, patchouli and tangerine peel in the pharmaceutical composition of the embodiment can more effectively improve the gastric emptying rate of mice in the range of 1-2:30-80:30-80:15-50.

[0152] Compared with the dose group (D6) in Comparative Example 6, the gastric emptying rate of mice in the dose group (S1-2) in Example 1 was significantly improved. This shows that the components of the pharmaceutical composition of the example interact with each other to more effectively improve the gastric emptying rate of mice and alleviate the symptoms of delayed gastric emptying in mice.

[0153] The above results show that the components of the pharmaceutical composition of the embodiment interact with each other and can significantly alleviate the reduced gastric emptying rate caused by indigestion. Furthermore, the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition is in the range of 1-3:1-10:1-3:0.5-5, which can more effectively improve the gastric emptying rate of mice. The mass ratio of magnolol, atractylodes, patchouli and tangerine peel in the pharmaceutical composition is in the range of 1-2:30-80:30-80:15-50, which can also more effectively improve the gastric emptying rate of mice.

[0154] 3.1.3 Effect of the drug composition on intestinal propulsion rate in young mice with dyspepsia

[0155] The intestinal propulsion rate of mice after five days of administration is as follows Figure 4 The results are as follows:

[0156] (1) Compared with the normal group, the intestinal propulsion rate of mice in the model control group (FD) was significantly reduced ( ### P<0.001).

[0157] The results showed that compared with the normal group, the intestinal propulsion rate of young mice was significantly reduced after modeling.

[0158] (2) Compared with the model control group, the intestinal propulsion rate of mice in the positive control group (Mosa), the low-dose group of Example 1 (S1-1), the medium-dose group of Example 1 (S1-2), the high-dose group of Example 1 (S1-3), the medium-dose group of Example 2-8 (S2-S8), and the medium-dose group of Comparative Example 1-6 (D1-D6) were significantly increased ( ** P < 0.01, *** P < 0.001). Among them, the intestinal propulsion rates of mice in the medium-dose groups (D1-D6) of Comparative Examples 1-6 were all lower than those in the low-dose group (S1-1) of Example 1, the medium-dose group (S1-2) of Example 1, the high-dose group (S1-3) of Example 1, and the medium-dose groups (S2-S8) of Examples 2-8.

[0159] The results showed that the pharmaceutical compositions of Examples 1-8 and Comparative Examples 1-6 of the present invention could alleviate the low intestinal propulsion rate of the model mice and significantly improve the intestinal propulsion rate of the mice. Among them, the pharmaceutical composition of Example 1 had the better effect.

[0160] (3) Further, the effects of the pharmaceutical compositions of Comparative Examples 1-6 on the intestinal propulsion rate of mice were compared, and it was found that the pharmaceutical composition of Comparative Example 6 had a more excellent effect. Therefore, the compositions of Comparative Example 6 were compared with those of Examples 1-8.

[0161] It was found that compared with the medium dose group (D6) of comparative example 6, the gastrointestinal propulsion rate of mice in the low dose group (S1-1) of example 1, the medium dose group (S1-2) of example 1, the high dose group (S1-3) of example 1, and the medium dose groups (S2-S8) of examples 2-8 were significantly increased ( + P<0.05, ++ P<0.01).

[0162] The results showed that the intestinal propulsion rate of mice in the medium-dose groups of Examples 1-8, the low-dose group of Example 1, and the high-dose group of Example 1 was significantly improved compared to the optimal group in the comparative example (i.e., Comparative Example 6). Therefore, compared with the medium-dose groups (D1-D5) of Comparative Examples 1-5, which were slightly worse than the medium-dose group (D6) of Comparative Example 6, the intestinal propulsion rate of mice in the medium-dose group (S1-2) of Example 1 was significantly improved.

[0163] Compared to the medium-dose groups (D1-D2) in Comparative Examples 1-2, the intestinal propulsion rate of mice in the medium-dose group (S1-2) in Example 1 was significantly improved. This indicates that the pharmaceutical composition of the Example, using ferulic acid, vanillic acid, and p-coumaric acid, interacts with other components to significantly improve the intestinal propulsion rate of mice.

[0164] Compared with the dose group (D3) in comparative example 3, the intestinal propulsion rate of mice in the dose group (S1-2) in Example 1 was significantly improved. This shows that the pharmaceutical composition of the example uses imperatorin, isoimperatorin and oxidized imperatorin, which interact with other components to significantly improve the intestinal propulsion rate of mice.

[0165] Compared with the dosage group (D4) in comparative example 4, the intestinal propulsion rate of mice in the dosage group (S1-2) in Example 1 was significantly improved, which indicates that the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition of the example can more effectively improve the intestinal propulsion rate of mice in the range of 1-3:1-10:1-3:0.5-5.

[0166] Compared with the dose group (D5) in comparative example 5, the intestinal propulsion rate of mice in the dose group (S1-2) in Example 1 was significantly improved, which indicates that the mass ratio of magnolia officinalis, atractylodes, patchouli and tangerine peel in the pharmaceutical composition of the embodiment can more effectively improve the intestinal propulsion rate of mice in the range of 1-2:30-80:30-80:15-50.

[0167] Compared with the dose group (D6) in comparative example 6, the intestinal propulsion rate of mice in the dose group (S1-2) in Example 1 was significantly improved, which indicates that the components in the pharmaceutical composition of the example interact with each other and can more effectively improve the intestinal propulsion rate of mice.

[0168] The above results show that the components of the pharmaceutical composition of the embodiment interact with each other and can significantly alleviate the reduced intestinal propulsion rate caused by indigestion. Furthermore, the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition in the range of 1-3:1-10:1-3:0.5-5 can more effectively improve the intestinal propulsion rate of mice. The mass ratio of magnolol, atractylodes, patchouli and tangerine peel in the pharmaceutical composition in the range of 1-2:30-80:30-80:15-50 can also more effectively improve the intestinal propulsion rate of mice.

[0169] 3.2 Effects of the drug combination on the expression of biomarkers in serum and gastric tissue of mice with functional dyspepsia

[0170] 3.2.1 Gastrin (GAS)

[0171] After five days of administration, the gastrin (GAS) levels of mice were Figure 5 The results are as follows:

[0172] (1) Compared with the normal group, the gastrin level of mice in the model control group (FD) was significantly decreased ( ### P<0.001).

[0173] The results showed that compared with the normal group, the gastrin level of young mice was significantly reduced after modeling.

[0174] (2) Compared with the model control group, the gastrin levels of mice in the positive control group (Mosa), the low-dose group of Example 1 (S1-1), the medium-dose group of Example 1 (S1-2), the high-dose group of Example 1 (S1-3), the medium-dose groups of Examples 2-8 (S2-S8), and the medium-dose groups of Comparative Examples 1-6 (D1-D6) were significantly increased ( * P<0.05, ** P < 0.01, *** P < 0.001). Among them, the gastrin levels of mice in the medium-dose groups (D1-D6) of Comparative Examples 1-6 were lower than those in the low-dose group (S1-1) of Example 1, the medium-dose group (S1-2) of Example 1, the high-dose group (S1-3) of Example 1, and the medium-dose groups (S2-S8) of Examples 2-8.

[0175] The results showed that the pharmaceutical compositions of Examples 1-8 and Comparative Examples 1-6 of the present invention could regulate and improve the gastrin secretion levels of the model group mice, and significantly increased the gastrin secretion of the mice. Among them, the pharmaceutical composition of Example 1 had the better effect.

[0176] (3) Further, the effects of the pharmaceutical compositions of Comparative Examples 1-6 on gastrin secretion in mice were compared, and it was found that the pharmaceutical composition of Comparative Example 6 had a more excellent effect. Therefore, the compositions of Comparative Example 6 were compared with those of Examples 1-8.

[0177] Compared with the medium dose group (D6) of Comparative Example 6, the gastrin levels of mice in the low dose group (S1-1) of Example 1, the medium dose group (S1-2) of Example 1, the high dose group (S1-3) of Example 1, and the medium dose groups (S2-S8) of Examples 2-8 were significantly increased ( + P<0.05, ++ P < 0.01, +++ P<0.001).

[0178] The results showed that the gastrin levels of mice in the medium-dose groups of Examples 1-8, the low-dose group of Example 1, and the high-dose group of Example 1 were significantly increased compared to the optimal group in the comparative example (i.e., Comparative Example 6). Therefore, compared to the medium-dose groups (D1-D5) of Comparative Examples 1-5, which were slightly worse than the medium-dose group (D6) of Comparative Example 6, the gastrin levels of mice in the medium-dose group (S1-2) of Example 1 were significantly increased.

[0179] Compared with the dose groups (D1-D2) in comparative examples 1-2, the gastrin level of mice in the dose group (S1-2) in Example 1 was significantly increased, indicating that the pharmaceutical composition of the example uses ferulic acid, vanillic acid, p-coumaric acid and other components to cooperate with each other, which can significantly promote gastrin secretion in mice.

[0180] Compared with the dose group (D3) in comparative example 3, the gastrin level of mice in the dose group (S1-2) in Example 1 was significantly increased, which indicates that the pharmaceutical composition of the example uses imperatorin, isoimperatorin and oxidized imperatorin, and the three interact with other components to significantly increase the gastrin secretion level of mice.

[0181] Compared with the dosage group (D4) in comparative example 4, the gastrin level of mice in the dosage group (S1-2) in Example 1 was significantly increased, which indicates that the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition of the example can more effectively promote gastrin secretion in mice in the range of 1-3:1-10:1-3:0.5-5.

[0182] Compared with the dose group (D5) in comparative example 5, the gastrin level of mice in the dose group (S1-2) in Example 1 was significantly increased, which indicates that the mass ratio of magnolol, atractylodes, patchouli and tangerine peel in the pharmaceutical composition of the embodiment can more effectively promote gastrin secretion in mice in the range of 1-2:30-80:30-80:15-50.

[0183] Compared with the dose group (D6) in comparative example 6, the gastrin level of mice in the dose group (S1-2) in example 1 was significantly increased, which indicates that the components in the pharmaceutical composition of the example interact with each other and can more effectively increase the gastrin secretion level of mice.

[0184] The above results show that the components of the pharmaceutical composition of the embodiment interact with each other and can significantly alleviate the reduced gastrin secretion caused by indigestion. Further, the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition is in the range of 1-3:1-10:1-3:0.5-5, which can more effectively improve the gastrin secretion level of mice. The mass ratio of magnolol, atractylodes, patchouli and tangerine peel in the pharmaceutical composition is in the range of 1-2:30-80:30-80:15-50, which can also more effectively improve the gastrin secretion level of mice.

[0185] 3.2.2 Motilin (MTL)

[0186] After five days of administration, the levels of motilin (MTL) in mice were as follows: Figure 6 The results are as follows:

[0187] (1) Compared with the normal group, the MTL level of mice in the model control group (FD) was significantly decreased ( ### P<0.001).

[0188] The results showed that compared with the normal group, the MTL level in young mice was significantly reduced after modeling.

[0189] (2) Compared with the model control group, the MTL levels of mice in the positive control group (Mosa), the low-dose group of Example 1 (S1-1), the medium-dose group of Example 1 (S1-2), the high-dose group of Example 1 (S1-3), the medium-dose groups of Examples 2-8 (S2-S8), and the medium-dose groups of Comparative Examples 1-6 (D1-D6) were significantly increased ( * P<0.05, ** P < 0.01, *** P < 0.001). Among them, the MTL levels of mice in the medium-dose groups (D1-D6) of Comparative Examples 1-6 were lower than those in the low-dose group (S1-1) of Example 1, the medium-dose group (S1-2) of Example 1, the high-dose group (S1-3) of Example 1, and the medium-dose groups (S2-S8) of Examples 2-8.

[0190] The results showed that the pharmaceutical compositions of Examples 1-8 and Comparative Examples 1-6 of the present invention could regulate and improve the MTL levels of model mice, significantly increasing the MTL levels of mice. Among them, the pharmaceutical composition of Example 1 had the better effect.

[0191] (3) Further, the effects of the pharmaceutical compositions of Comparative Examples 1-6 on the expression level of MTL in mice were compared, and it was found that the pharmaceutical composition of Comparative Example 6 had a more excellent effect.

[0192] Next, compared with the dosage group (D6) in Comparative Example 6, the MTL levels of the mice in the low dosage group (S1-1), the middle dosage group (S1-2), the high dosage group (S1-3) of Example 1, and the dosage groups (S2-S8) of Examples 2-8 were significantly increased + P < 0.05, ++ P < 0.01, +++ P < 0.001.

[0193] The results show that the MTL levels of the mice in the dosage groups of Examples 1-8, the low dosage group of Example 1, and the high dosage group of Example 1 are significantly improved compared with the optimal group (i.e., Comparative Example 6). Therefore, compared with the dosage groups (D1-D5) of Comparative Examples 1-5, which are slightly worse than the dosage group (D6) of Comparative Example 6, the MTL level of the mice in the middle dosage group (S1-2) of Example 1 is significantly improved.

[0194] Compared with the dosage groups (D1-D2) of Comparative Examples 1-2, the MTL level of the mice in the middle dosage group (S1-2) of Example 1 is significantly improved, which indicates that the pharmaceutical composition of the example, which uses ferulic acid, vanillic acid, and p-coumaric acid to interact with other components, can significantly improve the MTL level of mice.

[0195] Compared with the dosage group (D3) of Comparative Example 3, the MTL level of the mice in the middle dosage group (S1-2) of Example 1 is significantly improved, which indicates that the pharmaceutical composition of the example, which uses imperatorin, isoimperatorin, and oxymatrine, and the three interact with other components, can significantly improve the MTL level of mice.

[0196] Compared with the dosage group (D4) of Comparative Example 4, the MTL level of the mice in the middle dosage group (S1-2) of Example 1 is significantly improved, which indicates that the mass ratio of imperatorin, isoimperatorin, oxymatrine, and puerarin in the pharmaceutical composition of the example in the range of 1-3:1-10:1-3:0.5-5 can more effectively improve the MTL level of mice.

[0197] Compared with the dosage group (D5) of Comparative Example 5, the MTL level of the mice in the middle dosage group (S1-2) of Example 1 is significantly improved, which indicates that the mass ratio of magnolol, atractylodes, pachystachys, and citrus grandis in the pharmaceutical composition of the example in the range of 1-2:30-80:30-80:15-50 can more effectively improve the MTL level of mice.

[0198] Compared with the dosage group (D6) of Comparative Example 6, the MTL level of the mice in the middle dosage group (S1-2) of Example 1 is significantly improved, which indicates that the interaction of the components in the pharmaceutical composition of the example can more effectively improve the MTL level of mice.

[0199] The above results show that the components of the pharmaceutical composition of the embodiment interact with each other to significantly alleviate the reduction of MTL levels caused by indigestion. Furthermore, the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin, and puerarin in the pharmaceutical composition within the range of 1-3:1-10:1-3:0.5-5 can more effectively increase the MTL level of mice. The mass ratio of magnolol, atractylodes, patchouli, and tangerine peel in the pharmaceutical composition within the range of 1-2:30-80:30-80:15-50 can also more effectively increase the MTL level of mice.

[0200] 3.2.3 Interleukin-4 (IL-4)

[0201] After five days of administration, the levels of interleukin-4 (IL-4) in mice were as follows: Figure 7 The results are as follows:

[0202] (1) Compared with the normal group, the IL-4 level of mice in the model control group (FD) was significantly decreased ( ### P<0.001).

[0203] The results showed that compared with the normal group, the IL-4 level in young mice was significantly decreased after modeling.

[0204] (2) Compared with the model control group, the IL-4 levels of mice in the positive control group (Mosa), the low-dose group of Example 1 (S1-1), the medium-dose group of Example 1 (S1-2), the high-dose group of Example 1 (S1-3), the medium-dose group of Examples 2-8 (S2-S8), and the medium-dose group of Comparative Examples 1-4 (D1-D6) were significantly increased ( * P<0.05, ** P < 0.01, *** P < 0.01). Among them, the IL-4 levels of mice in the medium-dose groups (D1-D6) of Comparative Examples 1-6 were lower than those in the low-dose group (S1-1) of Example 1, the medium-dose group (S1-2) of Example 1, the high-dose group (S1-3) of Example 1, and the medium-dose groups (S2-S8) of Examples 2-8.

[0205] The results showed that the pharmaceutical compositions of Examples 1-8 and Comparative Examples 1-6 of the present invention could regulate and improve the IL-4 expression levels of the model group mice, significantly increasing the IL-4 levels of the mice. Among them, the pharmaceutical composition of Example 1 had the better effect.

[0206] (3) Further, the effects of the pharmaceutical compositions of Comparative Examples 1-6 on the expression level of IL-4 in mice were compared, and it was found that the pharmaceutical composition of Comparative Example 6 had a better effect.

[0207] Then, compared with the medium dose group (D6) in Comparative Example 6, the IL-4 levels of mice in the low dose group (S1-1) of Example 1, the medium dose group (S1-2) of Example 1, the high dose group (S1-3) of Example 1, and the medium dose groups (S2-S8) of Examples 2-8 were significantly increased ( + P<0.05, ++ P<0.01).

[0208] The results showed that the pharmaceutical compositions of Examples 1-8 all significantly increased IL-4 expression levels in mice compared to the optimal group in the comparative example (i.e., Comparative Example 6). Therefore, compared to the dose groups (D1-D5) in Comparative Examples 1-5, which were slightly inferior to the dose group (D6) in Comparative Example 6, the IL-4 levels in mice in the dose group (S1-2) in Example 1 were significantly increased.

[0209] Compared with the dose groups (D1-D2) in comparative examples 1-2, the IL-4 level of mice in the dose group (S1-2) in Example 1 was significantly increased, indicating that the pharmaceutical composition of the example uses ferulic acid, vanillic acid, p-coumaric acid and other components to cooperate with each other, which can significantly increase the IL-4 level of mice.

[0210] Compared with the dosage group (D3) in comparative example 3, the IL-4 level of mice in the dosage group (S1-2) in Example 1 was significantly increased, which indicates that the pharmaceutical composition of the example uses imperatorin, isoimperatorin and oxidized imperatorin, and the three interact with other components to significantly increase the IL-4 level of mice.

[0211] Compared with the dosage group (D4) in comparative example 4, the IL-4 level of mice in the dosage group (S1-2) in Example 1 was significantly increased, indicating that the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition of the example can more effectively increase the IL-4 level of mice in the range of 1-3:1-10:1-3:0.5-5.

[0212] Compared with the dose group (D5) in comparative example 5, the IL-4 level of mice in the dose group (S1-2) in Example 1 was significantly increased, indicating that the mass ratio of magnolol, atractylodes, patchouli and tangerine peel in the pharmaceutical composition of the embodiment can more effectively increase the IL-4 level of mice in the range of 1-2:30-80:30-80:15-50.

[0213] Compared with the dosage group (D6) in comparative example 6, the IL-4 level of mice in the dosage group (S1-2) in Example 1 was significantly increased, which indicates that the components in the pharmaceutical composition of the example interact with each other and can more effectively increase the IL-4 level of mice.

[0214] The above results show that the components of the pharmaceutical composition of the embodiment interact with each other and can significantly alleviate the decrease in IL-4 levels caused by indigestion. Furthermore, the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition is in the range of 1-3:1-10:1-3:0.5-5, which can more effectively increase the IL-4 level of mice. The mass ratio of magnolol, atractylodes, patchouli and tangerine peel in the pharmaceutical composition is in the range of 1-2:30-80:30-80:15-50, which can also more effectively increase the IL-4 level of mice.

[0215] 3.2.4 Interleukin (IL-1β) index

[0216] After five days of administration, the levels of interleukin (IL-1β) in mice were as follows: Figure 8 The results are as follows:

[0217] (1) Compared with the normal group, the IL-1β level of mice in the model control group (FD) was significantly increased ( ### P<0.001).

[0218] The results showed that compared with the normal group, the IL-1β level in young mice increased significantly after modeling.

[0219] (2) Compared with the model control group, the IL-1β levels of mice in the positive control group (Mosa), the low-dose group of Example 1 (S1-1), the medium-dose group of Example 1 (S1-2), the high-dose group of Example 1 (S1-3), the medium-dose groups of Examples 2-8 (S2-S8), and the medium-dose groups of Comparative Examples 1-6 (D1-D6) were significantly reduced ( * P<0.05, ** P < 0.01). Among them, the IL-1β levels of mice in the medium-dose groups (D1-D6) of Comparative Examples 1-6 were higher than those in the low-dose group (S1-1) of Example 1, the medium-dose group (S1-2) of Example 1, the high-dose group (S1-3) of Example 1, and the medium-dose groups (S2-S8) of Examples 2-8.

[0220] The results showed that the pharmaceutical compositions of Examples 1-8 and Comparative Examples 1-6 of the present invention could regulate the expression level of IL-1β in the model group mice and significantly reduce the secretion of IL-1β in the mice. Among them, the pharmaceutical composition of Example 1 had the better effect.

[0221] (3) Comparing the effects of the pharmaceutical compositions of Comparative Examples 1-6 on the expression level of IL-1β in mice, it was found that the pharmaceutical composition of Comparative Example 6 had the best effect. Then, Comparative Example 6 was compared with the pharmaceutical compositions of Examples 1-8.

[0222] It was found that compared with the medium dose group (D6) in comparative example 6, the IL-1β levels of mice in the low dose group (S1-1) of Example 1, the medium dose group (S1-2) of Example 1, the high dose group (S1-3) of Example 1, and the medium dose groups (S2-S8) of Examples 2-8 were significantly reduced ( + P<0.05, ++ P<0.01).

[0223] The results showed that the pharmaceutical compositions of Examples 1-8 all significantly reduced the IL-1β expression levels in mice compared to the optimal group in the comparative example (i.e., Comparative Example 6). Therefore, compared to the dose groups (D1-D5) in Comparative Examples 1-5, which were slightly worse than the dose group (D6) in Comparative Example 6, the IL-1β expression levels in mice in the dose group (S1-2) in Example 1 were significantly reduced.

[0224] Compared with the dose groups (D1-D2) in comparative examples 1-2, the IL-1β level of mice in the dose group (S1-2) in Example 1 was significantly reduced, indicating that the pharmaceutical composition of the example uses ferulic acid, vanillic acid, p-coumaric acid and other components to cooperate with each other, which can significantly reduce the secretion of IL-1β in mice.

[0225] Compared with the dose group (D3) in comparative example 3, the IL-1β level of mice in the dose group (S1-2) in Example 1 was significantly reduced, which indicates that the pharmaceutical composition of the example uses imperatorin, isoimperatorin and oxidized imperatorin, and the three interact with other components to significantly reduce the IL-1β secretion of mice.

[0226] Compared with the dosage group (D4) in comparative example 4, the IL-1β level of mice in the dosage group (S1-2) in Example 1 was significantly reduced, indicating that the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition of the example can more effectively reduce the IL-1β level of mice in the range of 1-3:1-10:1-3:0.5-5.

[0227] Compared with the dose group (D5) in comparative example 5, the IL-1β level of mice in the dose group (S1-2) in Example 1 was significantly reduced, indicating that the mass ratio of magnolia officinalis, atractylodes, patchouli and tangerine peel in the pharmaceutical composition of the embodiment can more effectively reduce the IL-1β level of mice in the range of 1-2:30-80:30-80:15-50.

[0228] Compared with the dosage group (D6) in comparative example 6, the IL-1β level of mice in the dosage group (S1-2) in example 1 was significantly reduced, which indicates that the components in the pharmaceutical composition of the example interact with each other and can more effectively reduce the IL-1β level of mice.

[0229] The above results show that the components of the pharmaceutical composition of the embodiment interact with each other and can significantly alleviate the increase in IL-1β levels caused by indigestion. Furthermore, the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition is in the range of 1-3:1-10:1-3:0.5-5, which can more effectively reduce the IL-1β level in mice. The mass ratio of magnolol, atractylodes, patchouli and tangerine peel in the pharmaceutical composition is in the range of 1-2:30-80:30-80:15-50, which can also more effectively reduce the IL-1β level in mice.

[0230] In summary, the components of the pharmaceutical composition of the embodiment interact with each other and can significantly alleviate the effects of indigestion. Furthermore, the mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin in the pharmaceutical composition is in the range of 1-3:1-10:1-3:0.5-5, which can more effectively alleviate indigestion in mice. The mass ratio of magnolol, atractylodes, patchouli and tangerine peel in the pharmaceutical composition is in the range of 1-2:30-80:30-80:15-50, which can also more effectively alleviate indigestion in mice.

[0231] Test Example 2

[0232] Take the pharmaceutical compositions obtained in Example 1 and Comparative Examples 1-6 respectively, add an appropriate amount of water, stir evenly, add 90 g of sucrose, dissolve it, then add 50 g of sorbitol 80, add water to 1000 mL, mix well, encapsulate, sterilize by autoclaving at 121 ° C, and encapsulate to obtain an aqueous solution of the pharmaceutical composition.

[0233] The mixture was placed at 30±2°C and relative humidity of 65±5%, and samples were taken for observation and testing at 0, 3, 6, 12, 18, 24, 30, 36, 42, and 48 months. The changes in the content of puerarin in the aqueous solution of the pharmaceutical composition were detected by liquid chromatography with reference to the 2020 Chinese Pharmacopoeia. The results are shown in Tables 4 and Figure 9 .

[0234] The conditions for liquid chromatography detection of puerarin were as follows: chromatographic column Agilent ZORBAX SB-C18 (4.6 mm × 250 mm, 5 μm), mobile phase methanol-water (25:75), detection wavelength 250 nm, column temperature 40°C, flow rate 1.0 mL / min.

[0235] Figure 9 The figure shows the loss rate of puerarin in the pharmaceutical composition over 48 months, wherein different letters between a and c indicate significant differences, and the significance level is α=0.05.

[0236] Figure 9The results shown in Table 4 indicate that the pharmaceutical compositions of the Examples have excellent stability and can be stored for long periods of time. After 48 months of storage, the loss rate of puerarin in the pharmaceutical compositions of Comparative Examples 1-3 and Comparative Examples 5-6 was significantly increased compared to Example 1. There was no significant difference in the loss rate of puerarin between the pharmaceutical compositions of Example 1 and Comparative Example 4.

[0237] Compared with Example 1, the pharmaceutical compositions of Comparative Examples 1-3 had the same puerarin content but different components, and the puerarin loss rate was significantly increased and the stability was significantly reduced. The results showed that the components in Example 1 interacted with each other, which was beneficial to improving the stability of puerarin.

[0238] Compared with Example 1, the pharmaceutical composition of Comparative Example 5 had the same puerarin content, but different component ratios. The puerarin loss rate was significantly increased, and the stability was significantly decreased. The results indicate that the components in Example 1 interact with each other at certain ratios, which helps improve the stability of puerarin.

[0239] Table 4 Detection results of puerarin content in the pharmaceutical composition

[0240]

[0241]

[0242] 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. A pharmaceutical composition for functional dyspepsia, characterized in that: The invention is composed of the following components in parts by weight: 13.0-14.5 parts of costus root, 13.0-14.5 parts of atractylodes, 5.5-9 parts of mint, 13.0-14.5 parts of patchouli, 6.0-7.8 parts of tangerine peel, 3.0-4.0 parts of Uncaria rhynchophylla, 3.0-4.0 parts of tribulus terrestris, 13.0-14.5 parts of Guangdong Shenqu, 6.0-7.5 parts of chrysanthemum, and 25-30 parts of poria , Radix Trichosanthis 9.5-11.0 parts, Semen Coicis 16-18 parts, Magnolia officinalis 0.25-0.40 parts, Imperatorin 0.2-1.1 parts, Isoperibolin 0.2-1.1 parts, Oxyimperatorin 0.2-1.1 parts, Ferulic acid 0.01-0.1 parts, Vanillic acid 0.01-0.1 parts, P-coumaric acid 0.01-0.1 parts and Puerarin 0.1-1.5 parts; The mass ratio of imperatorin, isoimperatorin, oxidized imperatorin and puerarin is 1-3:1-10:1-3:0.5-5; The mass ratio of magnolol, atractylodes, patchouli and red tangerine peel is 1-2:30-80:30-80:15-50.

2. The pharmaceutical composition according to claim 1, characterized in that The invention is composed of the following components by weight: 13.2-14.0 parts of costus root, 13.2-14.0 parts of atractylodes, 6.0-7.5 parts of mint, 13.2-14.0 parts of patchouli, 6.0-7.0 parts of red tangerine peel, 3.1-3.7 parts of Uncaria rhynchophylla, 3.1-3.7 parts of tribulus terrestris, 13.2-14.0 parts of Guangdong Shenqu, 6.5-7.0 parts of chrysanthemum, 26-28 parts of poria, 13.2-14.0 parts of chrysanthemum, 26-28 parts of tuckahoe ... 10.0-10.5 parts of pollen, 17.0-17.5 parts of coix seed, 0.25-0.40 parts of magnolol, 0.2-1.1 parts of imperatorin, 0.2-1.1 parts of isoimperatorin, 0.2-1.1 parts of oxidized imperatorin, 0.01-0.1 parts of ferulic acid, 0.01-0.1 parts of vanillic acid, 0.01-0.1 parts of p-coumaric acid and 0.1-1.5 parts of puerarin.

3. The method for preparing the pharmaceutical composition according to any one of claims 1 to 2, characterized in that: The following steps are involved: 1) distilling costus root, atractylodes lancea, mint, patchouli, and red tangerine peel, collecting volatile oil and residual substances, decocting the residual substances in water, concentrating the decoction, adding ethanol, collecting and concentrating the filtrate 1, and obtaining an extract 1; 2) decoct Uncaria rhynchophylla, Tribulus terrestris, Guangdong Shenqu (Shenqu) and chrysanthemum in water, concentrate the decoction, add ethanol, collect and concentrate filtrate 2 to obtain extract 2; 3) decocting coix seeds in water, concentrating the decoction, adding ethanol, collecting and concentrating the filtrate 3 to obtain extract 3; 4) Decoction of Poria cocos and Radix Trichosanthis in water, concentrate the decoction, add ethanol, collect and concentrate the filtrate 4 to obtain extract 4; 5) Evenly mix extract 1, extract 2, extract 3, extract 4, magnolol, imperatorin, isoimperatorin, oxyimperatorin, ferulic acid, vanillic acid, p-coumaric acid, and puerarin, then add volatile oil and mix evenly to obtain a pharmaceutical composition.

4. The preparation method according to claim 3, characterized in that In the step 1), the distillation time is 1-3 hours, the number of water decoctions is 1-3 times, and the volume fraction of ethanol in the filtrate 1 is 40-50%.

5. The preparation method according to claim 3, characterized in that: In the filtrate 2-4, the volume fraction of ethanol is 40-60%.

6. Use of the pharmaceutical composition according to any one of claims 1 to 2 or the pharmaceutical composition prepared by the preparation method according to any one of claims 3 to 5 in the preparation of a medicament for treating functional dyspepsia.

Images