Application of Wanshi insecticidal and food retention-removing pill in preparation of medicine

Abstract

The invention belongs to the technical field of traditional Chinese medicine, and relates to application of Wanshi insecticidal and food retention-removing pills in medicine preparation. The change of a model mouse before and after administration is researched to prove that the Wanshi insecticidal and food retention removing pill can remarkably improve functional dyspepsia, reduce triglyceride and low-density lipoprotein in a body and reduce the level of proinflammatory factors in the body; the safety evaluation of repeated administration proves that no obvious toxic reaction occurs after long-term use of the Wanshi insecticidal and food retention-removing pill. The invention provides a new application of the Wanshi insecticidal and food retention removing pill, is applied to preparation of medicines for treating functional dyspepsia, reducing triglyceride and low-density lipoprotein and / or resisting inflammation, and has important clinical value.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology and relates to the application of Wanshi Killing Insect and Eliminating Accumulation Pills in the preparation of medicines. Background Technology

[0002] Infantile malnutrition is a pediatric disease centered on spleen and stomach dysfunction. Its pathological process begins with spleen and stomach dysfunction, leading to impaired nutrient absorption and depletion of bodily resources. This process shows a high degree of similarity to functional dyspepsia (FD) in modern medicine, both involving gastrointestinal motility and digestive dysfunction as key links, manifesting as impaired digestion and food stagnation in the middle jiao (middle burner). While current Western medicines can alleviate symptoms, they have side effects on the nervous system and burden the liver and kidneys. Furthermore, children's blood-brain barrier is not fully developed, making them prone to adverse central nervous system reactions.

[0003] Low-density lipoprotein cholesterol (LDL) is a lipoprotein particle that carries cholesterol into peripheral tissue cells. When its level is too high, it easily deposits on the arterial walls, forming atherosclerotic plaques, which can lead to serious cardiovascular and cerebrovascular diseases such as coronary heart disease and stroke. Currently, clinical practice mainly uses chemically synthesized Western medicines such as statins to lower LDL. Although the efficacy is definite, there are potential adverse reactions such as liver damage and muscle toxicity, and long-term use can lead to drug resistance. Existing traditional Chinese medicine lipid-lowering preparations are mostly made from single herbs such as hawthorn, salvia miltiorrhiza, and cassia seed, or conventional compound preparations (such as Xuezhikang capsules and Dantian lipid-lowering pills). Their treatment methods are mostly based on resolving phlegm and removing blood stasis, without taking into account strengthening the spleen and harmonizing the stomach, regulating the function of the internal organs, and making it difficult to synergistically regulate lipid metabolism pathways, thus failing to achieve a comprehensive treatment. Summary of the Invention

[0004] In view of this, the purpose of this invention is to provide the application of Wanshi Killing Intestinal and Digestive Pills in the preparation of medicines, to solve the problems of side effects and metabolic disorders on organs and / or systems such as the nervous system, liver and kidneys in the prior art, and to provide new ideas for improving functional dyspepsia, reducing triglycerides and low-density lipoprotein in the body, and reducing the level of pro-inflammatory factors in the body, which has important clinical value.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0006] In a first aspect, the present invention provides the application of Wanshi Kill Insect and Eliminate Accumulation Pills in the preparation of medicines.

[0007] Preferably, the drug is selected from at least one of the following (A)-(B):

[0008] (A) Medications for functional dyspepsia;

[0009] (B) Drugs that lower low-density lipoprotein;

[0010] (C) Triglyceride-lowering drugs;

[0011] (D) Anti-inflammatory drugs.

[0012] Preferably, the drug further includes pharmaceutically acceptable excipients.

[0013] It should be noted that the drugs described in this invention can be prepared into suitable drug types by adding different types of pharmaceutically acceptable excipients. These drug types include, but are not limited to, the following: oral tablets (including but not limited to coated tablets), oral granules, oral powders, and injections (including but not limited to lyophilized powders for injection or emulsions for injection). These pharmaceutically acceptable excipients include, but are not limited to, diluents, wetting agents, binders, lubricants, solvents, solubilizers, cosolvents, emulsifiers, antioxidants, preservatives, local analgesics, pH adjusters, isotonic and / or isotonic regulators, etc. Further, the diluent is selected from starch, sucrose, and / or cellulose, etc.; the wetting agent is selected from water and / or ethanol, etc.; the binder is selected from starch paste, sugar, cellulose, and / or povidone, etc.; the lubricant is selected from talc, magnesium stearate, magnesium dodecyl sulfate, and / or micronized silica, etc.; the solvent is selected from water, ethanol, glycerol, propylene glycol, fatty oil, and / or ethyl acetate, etc.; the emulsifier is selected from glycerol fatty acid esters, higher fatty acid salts, sulfates, phospholipids, gelatin, pectin, agar, sodium alginate, and / or bentonite, etc.; the antioxidant is selected from sulfites, metabisulfites, and / or ascorbic acid, etc.; and the preservative is selected from parabens, sodium benzoate, quaternary ammonium compounds, alcohols, and / or phenols, etc.

[0014] More preferably, the dosage form of the drug is an oral dosage form or an injectable dosage form.

[0015] Compared with the prior art, the present invention has the following advantages:

[0016] The application of Wanshi Killing and Digestion-Eliminating Pills provided by this invention in the preparation of medicines shows that Wanshi Killing and Digestion-Eliminating Pills can significantly improve gastrointestinal motility disorders and synergistically alleviate the core symptoms of functional dyspepsia by bidirectionally regulating gastrointestinal hormones and optimizing intestinal flora, thus solving the problems of side effects on the nervous system and burden on the liver and kidneys in the prior art. Wanshi Killing and Digestion-Eliminating Pills can reduce the levels of triglycerides, low-density lipoprotein and pro-inflammatory factors and slow down weight gain, thus overcoming the limitations of incomplete treatment methods in the prior art of traditional Chinese medicine preparations, achieving both symptomatic and root cause treatment, and having good safety with long-term use, which has important clinical value. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 This is a graph showing the results of fecal condition in each group during a general observation experiment.

[0019] Figure 2 The graphs show the results of different hormone levels in each group during the gastrointestinal hormone level regulation experiment; Figure A shows the statistical analysis of motilin levels in serum samples; Figure B shows the statistical analysis of gastrin levels in serum samples; Figure C shows the statistical analysis of vasoactive peptide levels in serum samples; and Figure D shows the statistical analysis of cholecystokinin levels in serum samples.

[0020] Figure 3 The figures show the results of each group in the carbon residue retention rate and small intestinal propulsion rate test; Figure A is the statistical analysis chart of carbon residue retention rate; Figure B is the statistical analysis chart of small intestinal propulsion rate; Figure C is a photograph of the separated intestine.

[0021] Figure 4 Figure 1 shows the results of LEfSe analysis in the 16S rRNA sequencing analysis of cecal contents. Figure 2 shows the statistical analysis between the blank group and the model group; Figure 3 shows the statistical analysis between the domperidone group and the model group; Figure 4 shows the statistical analysis between the medium-dose group and the model group of Wanshi Insecticide and Digestive Pills; Figure 5 shows the statistical analysis between the high-dose group and the model group of Wanshi Insecticide and Digestive Pills.

[0022] Figure 5 Figure 1 shows the results of PCoA and NMDS analysis in the 16S rRNA sequencing analysis of cecal contents. Figure 2 shows the NMDS analysis of gut microbiota structure; Figure 3 shows the PCoA analysis of differences among gut microbiota groups; Figure 4 shows the relative abundance statistics of the top 10 dominant bacterial genera; and Figure 5 shows the comparison results of α diversity index.

[0023] Figure 6 This is a statistical graph showing the changes in body weight of mice in each group during the drug safety trial.

[0024] Figure 7The charts show the results of drug safety trials. Figure A shows the statistical analysis of changes in alanine aminotransferase (ALT) in serum samples; Figure B shows the statistical analysis of changes in aspartate aminotransferase (AST) in serum samples; Figure C shows the statistical analysis of changes in total bilirubin in serum samples; Figure D shows the statistical analysis of changes in direct bilirubin in serum samples; Figure E shows the statistical analysis of changes in the ratio of direct bilirubin to total bilirubin in serum samples; Figure F shows the statistical analysis of changes in urea in serum samples; Figure G shows the statistical analysis of changes in creatinine in serum samples; Figure H shows the statistical analysis of changes in triglycerides in serum samples; Figure I shows the statistical analysis of changes in total cholesterol in serum samples; Figure J shows the statistical analysis of changes in high-density lipoprotein (HDL) in serum samples; and Figure K shows the statistical analysis of changes in low-density lipoprotein (LDL) in serum samples.

[0025] Figure 8 Figure 1 shows the results of the cell experiment of Wanshi Kill Insect and Eliminate Accumulation Pills. Figure 2 shows the statistical analysis of triglyceride content in cell supernatant samples; Figure 3 shows the statistical analysis of TNF-α content in cell supernatant samples; Figure 4 shows the statistical analysis of IL-6 content in cell supernatant samples; Figure 5 shows the statistical analysis of IL-1β content in cell supernatant samples; Figure 6 shows the statistical analysis of Oil Red O staining area in cells; and Figure 7 shows the results of Oil Red O lipid staining. Detailed Implementation

[0026] The technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0027] It should be noted that the order of description of the following embodiments is not intended to limit the preferred order of embodiments. Furthermore, in the description of this invention, the term "comprising" means "including but not limited to". Various embodiments of the invention may exist in the form of a range; it should be understood that the description in the form of a range is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of the invention; therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and single numerical values ​​within that range. For example, it should be considered that the range description from 1 to 6 has specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and single digits within the range, such as 1, 2, 3, 4, 5, and 6, regardless of the range. Additionally, whenever a numerical range is indicated herein, it means including any referenced number (fraction or integer) within the indicated range.

[0028] The following specific embodiments further illustrate the application of the present invention, Wanshi Killing and Accumulating Pills, in the preparation of medicines. This section further illustrates the content of the present invention in conjunction with specific embodiments, but should not be construed as limiting the present invention. Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art, such as the conditions described in *Molecular Cloning: A Laboratory Manual (Fourth Edition)* published by Cold Spring Harbor Laboratory or the conditions recommended by the manufacturer. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in the art.

[0029] In the following examples, the L-arginine modeling method was described in reference ([1] Wu Yang, Ma Xueqin, Wang Yang, et al. Effects of Weiyuanning on gastrointestinal motility and gastrointestinal hormone secretion in mice with functional dyspepsia [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2014, 20(24): 185-189.).

[0030] In the following embodiments, the formulas for calculating the carbon residue retention rate and the small intestinal propulsion rate are as follows:

[0031] ;

[0032] .

[0033] In the following embodiments, the CTAB method was described in reference ([2] Wu Minna, Wu Yaqi, Qu Yan, et al. Comparison of four methods for extracting DNA from mouse intestinal microorganisms [J]. Journal of Ecology, 2015, 34(04):1183-1188.DOI:10.13292 / j.1000-4890.20150311.036.).

[0034] In the following examples, all data are expressed as mean ± standard deviation (Mean ± SD); statistical analysis was performed using GraphPad Prism 8 software (GraphPad Software, LLC., USA); one-way ANOVA was used for comparisons among multiple groups, and Tukey's post-hoc test was used for pairwise comparisons if significant differences were found; P < 0.05 indicated statistical significance. "Indicates a significant difference (P < 0.05)" "Indicates a highly significant difference (P < 0.01)" "" indicates a highly significant difference (P < 0.001).

[0035] Example

[0036] 1. Mouse animal modeling and grouping

[0037] Sixty male mice (KM Mice, Beijing Vital River Laboratory Animal Technology Co., Ltd., strain number: 202) were randomly divided into four groups: control group, model group, low-dose Wanshi Xiaoji Pill group (M-WSXP-L group), medium-dose Wanshi Xiaoji Pill group (M-WSXP-M group), high-dose Wanshi Xiaoji Pill group (M-WSXP-H group), and domperidone group (positive control group, M-Domperidone group), with 10 mice in each group.

[0038] The body weight (kg) of each mouse was measured. Except for the control group, FD model mice were established using the L-arginine modeling method. Gavage administration began the day after model establishment and continued for 7 days, with the specific administration regimen as follows:

[0039] (1) The blank group and the model group were given the same amount of distilled water;

[0040] (2) Based on the body weight of the mice in each Wanshi Insecticide and Digestive Pill administration group, Wanshi Insecticide and Digestive Pill (Wanmizhai Hospital, Luotian County, Huanggang City, Hubei Province, production date: 202504002) was administered in proportion to the clinical equivalent dose (M-WSXP-L group, 3g / kg), the clinical double dose (M-WSXP-M group, 6g / kg) and the clinical quadruple dose (M-WSXP-H group, 12g / kg);

[0041] (3) The positive drug group was given domperidone (5mg / kg, Shanxi Baotai Pharmaceutical Co., Ltd., batch number 20250101).

[0042] 2. Drug efficacy testing

[0043] 2.1 General State Observation

[0044] The general condition of mice in each group was observed, including hair and fecal condition, and evaluated and scored. The scoring scale for general condition is shown in Table 1. Before drug administration, all groups except the control group were scored out of 10. After drug administration, the scores for each mouse were accumulated, and the average score within each group was taken.

[0045] Table 1: Mouse General Condition Rating Scale

[0046]

[0047] Figure 1The results of fecal condition in each group during the general condition observation test are shown in the figure. Table 2 shows the body weight and general condition score of each group during the general condition observation test. The results show that, compared with the model group, the mental state of mice in the three groups of Wanshi Kill Insect and Accumulate-Eliminating Pills and the Domperidone group gradually recovered, some of their fur became dull, their weight gain trend stabilized (Table 2), and their fecal volume was normal and formed into pellets. Figure 1 The perianal area is clean.

[0048] Table 2: Weight and General Condition Scores for Each Group

[0049]

[0050] 2.2 Regulation of gastrointestinal hormone levels

[0051] Blood samples were collected from mice in each group, centrifuged, and serum samples were obtained. The levels of motilin (MTL), gastrin (GAS), cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) in the serum samples were detected using the following kits: Mouse Motilin ELISA Kit (Wuhan Beinlai Biotechnology Co., Ltd., catalog number: MU30329), Mouse Gastrin ELISA Kit (Wuhan Beinlai Biotechnology Co., Ltd., catalog number: MU30444), Mouse Cholecystokinin ELISA Kit (Wuhan Beinlai Biotechnology Co., Ltd., catalog number: MU30355), and Mouse Vasoactive Intestinal Peptide ELISA Kit (Wuhan Beinlai Biotechnology Co., Ltd., catalog number: MU30064).

[0052] Figure 2 The results of different hormone levels in each group during the gastrointestinal hormone level regulation experiment are shown in the following graphs: Graph A shows the statistical analysis of motilin levels in serum samples; Graph B shows the statistical analysis of gastrin levels in serum samples; Graph C shows the statistical analysis of vasoactive peptide levels in serum samples; and Graph D shows the statistical analysis of cholecystokinin levels in serum samples. The results show that, compared with the control group, the model group mice had significantly higher levels of MTL (motilin) ​​in their serum. Figure 2 (Figure A in the diagram) and GAS ( Figure 2 The levels of VIP (Figure B) decreased significantly by 47.4% and 38.7% (P < 0.01), while VIP (Figure B) Figure 2 (C diagram in the image) and CCK ( Figure 2 The levels of MTL and GAS in the D-plot were significantly increased by 68.9% and 65.2% respectively (P < 0.001); compared with the model group, all drug-treated groups significantly increased the levels of MTL and GAS, and significantly decreased the levels of VIP and CCK. Figure 2The results showed that Wanshi Kill Insect and Eliminate Indigestion Pills have a positive effect on gastric acid secretion and promote gastric emptying.

[0053] 2.3 Detection of carbon residue retention rate and small intestinal propulsion rate

[0054] Following the method described in the literature ([1] Wu Yang, Ma Xueqin, Wang Yang, et al. Effects of Weiyuanning on gastrointestinal motility and gastrointestinal hormone secretion in mice with functional dyspepsia [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2014, 20(24): 185-189.), mice in each group were administered gavage, the stomach and small intestine were separated, the total weight and net weight of the stomach were weighed, and the distance of small intestine and carbon particles movement (distance from the pylorus to the front end of the carbon particles) were measured. The carbon particle retention rate (%) and small intestinal propulsion rate (%) were calculated. The separated intestine (from the pylorus to the ileocecal junction) was laid flat on a measuring plate for photographic recording. The total length of the small intestine and the distance of carbon particles movement were measured using ImageJ software (https: / / imagej.net / ).

[0055] Figure 3 The results of the carbon residue retention rate and small intestinal propulsion rate tests for each group are shown in the figure. Figure A shows the statistical analysis of carbon residue retention rate; Figure B shows the statistical analysis of small intestinal propulsion rate; and Figure C shows a photograph of the separated intestine. The results showed that compared with the control group, the carbon residue retention rate in the model group increased significantly by 43.8% (P<0.01). Figure 3 (Figure A in the diagram) Small intestinal motility decreased by 15% (P<0.01). Figure 3 Figure B in the figure shows that the FD model mice obtained in this embodiment are reliable; compared with the model group, the small intestinal propulsion rate of the low, medium and high dose groups of Wanshi Killing and Accumulating Pills and the domperidone group were significantly increased by 17.5%, 26.3%, 28.1% and 15.8% respectively (P<0.001, Figure 3 (Figure B in the figure) The carbon residue rates in the high-dose group of Wanshi Insecticide and Digestive Pill and the domperidone group were significantly reduced by 31.7% and 23%, respectively (P<0.05). Figure 3 (See Figure A in the table). The results showed that after intervention with Wanshi Kill Insect and Eliminate Indigestion Pills, the above-mentioned gastrointestinal dysfunctions were improved to varying degrees, and the high-dose group had the most significant effect, which was comparable to that of the domperidone group.

[0056] 2.4 16S rRNA sequencing analysis of cecal contents

[0057] Mice were euthanized under anesthesia, and the contents of the ileocecal intestinal tract were collected. Genomic DNA was extracted from the samples using the CTAB method, and DNA samples that passed purity and concentration tests were used for subsequent experiments. Based on the characteristics of the 16S region, a small fragment library was constructed using a 16S (V3V4) bacterial amplicon library construction kit (Shanghai Yisheng Biotechnology Co., Ltd., catalog number: 12983ES96). Based on the constructed small fragment library, paired-end sequencing was performed using the Illumina NovaSeq sequencing platform (Illumina, Inc., model: NovaSeq6000). LEfSe analysis was used to assess the changes in cecal contents microbiota in different groups; PCoA and NMDS analyses were used to assess the β-diversity of cecal contents microbiota in different groups.

[0058] Figure 4 The results of the 16S rRNA sequencing analysis of cecal contents based on LEfSe analysis are shown in the figure. Figure A shows the statistical analysis between the blank group and the model group; Figure B shows the statistical analysis between the domperidone group and the model group; Figure C shows the statistical analysis between the medium-dose group and the model group of Wanshi Xiaoji Pills; Figure D shows the statistical analysis between the high-dose group and the model group of Wanshi Xiaoji Pills. "LDA SCORE" in the figures indicates the magnitude of the linear discriminant analysis effect; a higher value indicates a greater influence of the marker on the differences between groups. The results show that both medium and high-dose intervention with Wanshi Xiaoji Pills specifically enriched the probiotic Akkermansia muciniphila, showing a significant increase across the entire taxonomic unit from the phylum level (p_Verrucomicrobiota) to the genus level (g_Akkermansia). Figure 4 The results showed that Wanshi Kill Insect and Eliminate Accumulation Pills improved FD-related dysbiosis by specifically promoting the growth of this key beneficial bacteria with mucosal repair function.

[0059] Figure 5 The results of PCoA and NMDS analysis in the 16S rRNA sequencing analysis of cecal contents are shown. Figure A shows the NMDS analysis of gut microbiota structure; Figure B shows the PCoA analysis of differences among gut microbiota groups; Figure C shows the relative abundance statistical analysis of the top 10 dominant bacterial genera, where "Relative abundance" indicates relative abundance; Figure D shows the comparison results of the α diversity index; in the figures, "M_B" represents the low-dose group of Wanshi Xiaoji Wan, "M_C" represents the high-dose group, and "M_P" represents the domperidone group. The results show that the sample points in the model group were significantly separated from the control group. Figure 5 Figure A in the middle~ Figure 5Figure B in the figure shows that the FD model significantly altered the overall gut microbiota structure; regarding α-diversity, compared to the control group, the model group showed significantly higher species richness indices (ACE and Chao1) and comprehensive diversity indices (Shannon and Simpson). Figure 5 (Figure D in the diagram); phylum-level compositional analysis showed that, compared with the control group, the relative abundance of several gut health-related phyla (e.g., Verrucomicrobiota, associated with the intestinal barrier, Actinobacteriota, containing probiotics) was reduced in the model group. Figure 5 (Figure C in the diagram).

[0060] 3. Drug safety

[0061] Following the grouping method described in Chapter 1, male Kunming mice were randomly divided into three groups: a control group, a low-dose group (WSXP-L group), and a medium-dose group (WSXP-M group), with 10 mice in each group. The mice were administered the drugs according to the dosages described in Chapter 1 and the methods outlined in the literature (Technical Guidelines for Repeated-Dose Toxicity Studies of Drugs [EB / OL]. 2014-05-13) for one month, during which time changes in mouse body weight were monitored. Serum samples were collected according to the method described in Section 2 of Chapter 2. Liver function indicators (ALT, AST, TBIL, DBIL, DBIL / TBIL), kidney function indicators (UREA, CREA), and blood lipid indicators (TG, T-CHO, HDL, LDL) were measured using a fully automated biochemical analyzer (Shenzhen Leidu Life Science Co., Ltd., model: Chemray 240).

[0062] Figure 6 The chart shows the weight changes of mice in each group during the drug safety test. The results show that the weight of mice in all groups increased during the test, but the weight of the WSXP-L group and the WSXP-M group decreased by 5.6% and 3.3% respectively after 30 days of administration compared with the average weight of the control group, indicating that Wanshi Killing Insect and Eliminating Accumulation Pills can slow down the weight gain of mice.

[0063] Figure 7The results of the drug safety test are shown in the following graphs: Graph A shows the statistical analysis of changes in alanine aminotransferase (ALT) in serum samples; Graph B shows the statistical analysis of changes in aspartate aminotransferase (AST) in serum samples; Graph C shows the statistical analysis of changes in total bilirubin in serum samples; Graph D shows the statistical analysis of changes in direct bilirubin in serum samples; Graph E shows the statistical analysis of changes in the ratio of direct bilirubin to total bilirubin in serum samples; Graph F shows the statistical analysis of changes in urea in serum samples; Graph G shows the statistical analysis of changes in creatinine in serum samples; Graph H shows the statistical analysis of changes in triglycerides in serum samples; Graph I shows the statistical analysis of changes in total cholesterol in serum samples; Graph J shows the statistical analysis of changes in high-density lipoprotein (HDL) in serum samples; and Graph K shows the statistical analysis of changes in low-density lipoprotein (LDL) in serum samples. The results showed that, compared with the control group, the liver function indicators ( Figure 7 Figure A in the middle~ Figure 7 Figure E in the diagram), renal function indicators ( Figure 7 F diagram in the middle~ Figure 7 (G diagram in the image) and some blood lipid indicators ( Figure 7 H diagram in the middle~ Figure 7 The J-figure in the figure showed no significant changes, indicating that Wanshi Kill Insect and Eliminate Accumulation Pills had no significant effect on the health of mice. Furthermore, compared with the blank group, the triglyceride (TG) levels in both the WSXP-L and WSXP-M groups decreased in a dose-dependent manner. Figure 7 (H-plot in the image), and the LDL level in the WSXP-M group was significantly lower (P<0.05, Figure 7 (See K diagram). The results show that Wanshi Insecticide and Digestive Pills have a certain effect on reducing TG and can specifically reduce LDL in serum.

[0064] 4. The lipid-lowering and anti-inflammatory effects of Wanshi Killer and Digestive Pills (WSXP)

[0065] Based on the inhibitory effect of Wanshi Killing and Digestion-Eliminating Pills (WSXP) on serum triglycerides (TG) observed in Example 3, this example further explores the potential lipid-lowering and anti-inflammatory effects of Wanshi Killing and Digestion-Eliminating Pills at the cellular level. The specific methods are as follows: High-lipidemia model groups of HepG2 cells (Beijing Solarbio Science & Technology Co., Ltd., catalog number: C3461) were induced using a cell high-lipidemia induction kit (Beijing Solarbio Science & Technology Co., Ltd., catalog number: SCC-110211). A positive control group was set up, which was induced with high-lipidemia and then administered 10 μM atorvastatin. A negative control group was set up, which was not induced with high-lipidemia and did not receive any administration. Triglyceride Colorimetric Assay Kit (Wuhan Yilairuit Biotechnology Co., Ltd., catalog number: E-BC-K261-M), Human TNF-α ELISA Kit (Wuhan Yilairuit Biotechnology Co., Ltd., catalog number: E-EL-H0109), and Human IL-6 ELISA Kit were used. The levels of TG, TNF-α, IL-6, and IL-1β in each group of samples were measured using the Kit (Wuhan Elite Biotechnology Co., Ltd., catalog number: E-EL-H61) and the Human IL-1β ELISA Kit (Wuhan Elite Biotechnology Co., Ltd., catalog number: E-EL-H0149), respectively. Cell lipid staining was performed using the Oil Red O cell staining kit (Shanghai Beyotime Biotechnology Co., Ltd., catalog number: C0157S).

[0066] Figure 8The results of the cell experiments using Wanshi Insecticide and Digestive Pills are shown in the following figures: Figure A is a statistical analysis of the triglyceride content in the cell supernatant sample; Figure B is a statistical analysis of the TNF-α content in the cell supernatant sample; Figure C is a statistical analysis of the IL-6 content in the cell supernatant sample; Figure D is a statistical analysis of the IL-1β content in the cell supernatant sample; Figure E is a statistical analysis of the Oil Red O staining area of ​​the cells; Figure F is a result of Oil Red O lipid staining. In Figures A-E: "Sodium oleate" indicates sodium oleate induction treatment, "sodium palmitate" indicates sodium palmitate induction treatment, "Lipitor (10 μM)" indicates treatment with atorvastatin at a dose of 10 μM, "+" indicates the presence of this treatment, and "-" indicates the absence of this treatment. In Figure F: "Control" indicates the negative control group, "Model" indicates the model group, "WSXP" indicates different doses of Wanshi Insecticide and Digestive Pills treatment groups, and "Lipitor" indicates the positive control group. The results showed that after combined induction with sodium oleate and sodium palmitate, the levels of TG and pro-inflammatory factors (TNF-α, IL-6, IL-1β) in the cell supernatant samples of the model group were significantly increased; compared with the model group, all WSXP-treated groups effectively inhibited the accumulation of TG and the release of all pro-inflammatory factors in the cell supernatant samples, and this inhibitory effect showed a dose-dependent effect. Figure 8 Figure A in the middle - Figure 8 (Figure D in the diagram); Oil Red O lipid staining results showed that a large number of lipid droplets stained red were visible in the model group cells, while the accumulation of lipid droplets in the cells of each group treated with WSXP was significantly reduced (Figure D in the diagram). Figure 8 (Figure F in the figure); Among them, the WSXP treatment group with a dose of 1 mg / mL significantly reduced the intracellular Oil Red O staining positive area, and its effect was better than that of the positive control group (Figure F in the figure). Figure 8 (See Figure E in the original text). The results show that Wanshi Killing Insect and Accumulating Pills have a significant dual effect of reducing triglyceride accumulation and anti-inflammatory response in the cell model, which provides direct in vitro evidence for the lipid-lowering effect observed in the animal experiments in the aforementioned examples.

[0067] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. Use of Wan's Shicheng Xiaji Pill in the preparation of a medicament.

2. Use according to claim 1, wherein The medicament is selected from at least one of the following (A) - (B): (A) a functional dyspepsia medicament; (B) a low-density lipoprotein-lowering medicament; (C) a triglyceride-lowering medicament; (D) an anti-inflammatory medicament.

3. Use according to claim 1 or 2, characterized in that, The medicament further includes a pharmaceutically acceptable excipient.

4. The use according to claim 3, wherein the compound is ###0002### The medicament is in the form of an oral dosage form or an injectable dosage form.

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