A pharmaceutical composition for preventing or treating metabolic-related fatty liver disease

Abstract

The present application discloses a pharmaceutical composition for preventing or treating metabolic-related fatty liver disease, and relates to the use of smilax china saponin in the preparation of an anti-metabolism-related fatty liver disease synergist. Smilax china saponin can form a synergistic anti-metabolism-related fatty liver disease effect with a compound, and has a synergistic effect on the anti-metabolism-related fatty liver disease effect of dihydromyricetin. The present application also discloses a pharmaceutical composition for preventing or treating metabolic-related fatty liver disease, comprising dihydromyricetin and smilax china saponin, which can be used as an active ingredient for preventing or treating metabolic-related fatty liver disease and has a wide range of uses.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to a pharmaceutical composition for preventing or treating metabolism-related fatty liver disease, an application of smilax china saponin in the preparation of an anti-metabolism-related fatty liver disease synergist, and the use of smilax china saponin as an anti-metabolism-related fatty liver disease synergist in combination with an anti-metabolism-related fatty liver disease drug to form a synergistic anti-metabolism-related fatty liver disease effect. Background Art

[0002] Metabolic fatty liver disease (MAFLD) is rapidly increasing worldwide and is the most common liver disease. Obesity, type 2 diabetes, hyperlipidemia, and hypertension are highly prevalent in patients with MAFLD, and thus the risk factors for MAFLD are almost identical to those constituting metabolic syndrome. MAFLD is a complex spectrum of liver disease, ranging from benign, usually asymptomatic steatosis to more aggressive necroinflammatory forms, further progressing to fibrosis, cirrhosis, and even MAFL-related hepatocellular carcinoma and end-stage liver disease. However, to date, no drug has been approved for the treatment of MAFLD, and due to the slow progress in treatment, MAFLD is classified as a medical condition with unmet treatment needs.

[0003] At present, a large number of studies have been conducted on the effects of botanicals on metabolic-related fatty liver disease, proving that a variety of botanicals have significant effects on metabolic-related fatty liver disease in vitro and animal experiments. Clinical observations have also yielded promising results, demonstrating the great potential of natural medicines for the treatment of metabolic-related fatty liver disease.

[0004] Dihydromyricetin (DMY, C 15 H 12 O8) is the flavonoid with the highest content in the plant Grapevine, which is used to make vine tea. It has antioxidant stress, anti-inflammatory, anti-apoptotic and anti-cancer activities and can be effectively used to treat heart disease, diabetes, cerebral ischemia and various cancers. Modern pharmacological studies have shown that dihydromyricetin also has a strong liver protective effect.

[0005] The document Steroidal saponins from the roots of Smilax sp.: Structure and bioactivity. (Victoria L. Challinor et al. Steroids. 77 (2012) 504-511) reported that sarsaponins were extracted and purified from plants of the genus Smilax, and their anti-tumor cell activity was studied. Currently, there is no report on the prevention or treatment of metabolic-related fatty liver disease by sarsaponins, nor is there a report on the combination of sarsaponins and other active ingredients to prevent or treat metabolic-related fatty liver disease. Summary of the invention

[0006] Technical issues solved:

[0007] The present application aims at the deficiencies of the prior art and solves the technical problems that there is currently no drug approved for the treatment of metabolism-related fatty liver disease, etc., and provides a pharmaceutical composition for preventing or treating metabolism-related fatty liver disease, and the use of smilax china saponin in the preparation of an anti-metabolism-related fatty liver disease enhancer. Furthermore, dihydromyricetin and smilax china saponin are formed into a pharmaceutical composition for the preparation of an efficient drug for preventing or treating metabolism-related fatty liver disease.

[0008] Technical solution:

[0009] To achieve the above objectives, this application is implemented through the following technical solutions:

[0010] Application of sarsaparilla saponins in the preparation of synergists against metabolic-related fatty liver disease.

[0011] Furthermore, sarsaponin is used as an anti-metabolism-related fatty liver disease synergist in combination with an active compound for anti-metabolism-related fatty liver disease to form a pharmaceutical composition for synergistic anti-metabolism-related fatty liver disease.

[0012] Furthermore, the active compound against metabolism-related fatty liver disease is dihydromyricetin.

[0013] Another object of the present invention is to provide a pharmaceutical composition for preventing or treating metabolism-related fatty liver disease, comprising dihydromyricetin and sarsaponin.

[0014] Furthermore, the weight ratio of the dihydromyricetin to smilaxonin is 1:0.5-2.

[0015] Furthermore, the weight ratio of dihydromyricetin to smilaxonin is 1:1.

[0016] Furthermore, the metabolism-related fatty liver disease is metabolism-related fatty liver hepatitis.

[0017] Furthermore, the pharmaceutical composition also contains pharmaceutically acceptable excipients.

[0018] Furthermore, the pharmaceutical composition is administered orally or parenterally.

[0019] Furthermore, the oral or non-oral administration is specifically by subcutaneous injection, intramuscular injection, intravenous injection, oral administration, rectal administration, vaginal administration, nasal administration or transdermal administration.

[0020] Beneficial effects:

[0021] The present application provides a pharmaceutical composition for preventing or treating metabolic-related fatty liver disease, which, compared with the prior art, has the following

[0022] Beneficial effects:

[0023] 1. The present study shows that the combined use of sarsaponin and dihydromyricetin to treat LDLr - / - Mice were fed a high-fat diet for 12 weeks to establish a metabolic-associated fatty liver disease model. At a lower dose, smilax china saponins showed a significant synergistic effect on the protective effect of dihydromyricetin on metabolic-associated fatty liver disease.

[0024] 2. The combination of dihydromyricetin and sarsaponin has a significant improvement effect on serum metabolic parameters, and the metabolic parameter values ​​are significantly lower than those of the single dihydromyricetin drug group at the same dose.

[0025] 3. The combination of dihydromyricetin and smilax china saponin significantly reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), markers of liver damage, in serum. The levels of ALT and AST were significantly lower than those of the single dihydromyricetin drug group at the same dose.

[0026] 4. The combination of dihydromyricetin and sarsaponin significantly reduced the levels of triglyceride (TG) and cholesterol (TC) in the liver. The levels of TC and TG were significantly lower than those of the single dihydromyricetin drug group at the same dose.

[0027] 5. The combination of dihydromyricetin and sarsaponin significantly reduced the levels of inflammatory factors tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in the liver. The levels of TNF-α and IL-6 were significantly lower than those of the single dihydromyricetin drug group at the same dose.

[0028] 6. The combination of dihydromyricetin and sarsaparilla saponin significantly reduced the content of hydroxyproline, a marker of liver collagen deposition, and the hydroxyproline content was significantly lower than that of the single dihydromyricetin drug group at the same dose. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is the structural formula of sarsaparilla saponin of this application. DETAILED DESCRIPTION

[0030] The specific steps of the present invention are described below by way of examples, but are not limited to the examples.

[0031] The terms used in the present invention, unless otherwise specified, generally have the meanings commonly understood by those of ordinary skill in the art.

[0032] The present invention will be further described in detail below in conjunction with specific examples and with reference to data. It should be understood that these examples are only intended to illustrate the present invention and are not intended to limit the scope of the present invention in any way.

[0033] In the following examples, various processes and methods not described in detail are conventional methods well known in the art.

[0034] In this embodiment, smilax saponin was extracted and purified according to the method disclosed in the literature Steroidal saponins from the roots of Smilax sp.: Structure and bioactivity. (Victoria L. Challinor et al. Steroids. 77 (2012) 504-511).

[0035] Dihydromyricetin was purchased from Nanjing Dierge Pharmaceutical Technology Co., Ltd.

[0036] Healthy male LDLr - / - Mice were purchased from the Model Animal Research Institute of Nanjing University and the model was established at 12 months of age. The breeding environment was light and dark alternating every 12 hours.

[0037] Triglyceride (TG) (Product No. A110-1-1), cholesterol (TC) (Product No. A111-1-1), alanine aminotransferase (ALT) (Product No. C009-2-1) and aspartate aminotransferase (AST) (Product No. C010-2-1), hydroxyproline (HYP) (Product No. A030-2-1) test kits: purchased from Nanjing Jiancheng Biotechnology Co., Ltd.

[0038] Mouse insulin Elisa kit: purchased from Millipore, USA.

[0039] Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) Elisa kits: purchased from Jiangsu Haimen Biyuntian Biotechnology Research Institute.

[0040] Detection of lipid content in serum and liver: Take the serum samples that have been stored in aliquots, and detect the TG and TC content in serum and the TG and TC content in liver according to the instructions of the kit. Convert the absorbance into the respective content.

[0041] Elisa method to detect fasting insulin content, the steps are:

[0042] Step 1: Take out the 96-well plate and add 10 μl Assay buffer to the NSB well and sample well;

[0043] Step 2: Add 10 μl of Matrix Solution to the Standard, control and NSB wells;

[0044] Step 3: Add 10 μl insulin standard to the preset wells;

[0045] Step 4: Add 10 μl QC1 and QC2 to the preset wells;

[0046] Step 5: Add 10 μl of sample to the remaining wells;

[0047] Step 6: Add 80 μl of antibody to all wells, seal the wells, and incubate at room temperature for 2 hours;

[0048] Step 7: Pour the solution in the 96-well plate, tap to remove the remaining liquid, and wash 3 times with TBST;

[0049] Step 8: Add 100 μl of streptavidin-horseradish peroxidase conjugate solution to each well and incubate at room temperature for 30 minutes;

[0050] Step 9: Pour the solution in the 96-well plate, tap to remove the remaining liquid, and wash 6 times with TBST;

[0051] Step 10: Add 100 μl of 3,3',5,5'-tetramethylbenzidine solution to each well and incubate at room temperature for 15 minutes;

[0052] Step 11: Add 100 μl 0.3 M HCL stop solution to each well and read the light absorption value at 450 nm and 590 nm using a microplate reader;

[0053] Step 12: Calculate the insulin concentration in each well based on the absorbance value.

[0054] Fasting blood glucose determination: Fasting blood glucose was determined using an automatic biochemical analyzer.

[0055] Detection of ALT and AST content in serum: The levels of ALT and AST in serum were detected by the Reitman method according to the kit instructions.

[0056] Liver TNFα and IL-6 detection, steps are:

[0057] Step 1: Add 100 μl of sample per well, mix the 96-well plate thoroughly and incubate at 37°C for 40 minutes;

[0058] Step 2: Wash 4-6 times with TBST;

[0059] Step 3: Add distilled water and 100 μl of TNFα or IL-6 biotinylated antibody to each well;

[0060] Step 4: Mix the 96-well plate thoroughly and incubate at 37°C for 20 minutes;

[0061] Step 5: Wash the reaction plate 4-6 times with TBST;

[0062] Step 6: Add 100 μl of horseradish peroxidase-labeled Streptavidin to each well and place in the dark at 37°C for 20 minutes;

[0063] Step 7: Add 100 μl / well of TMB solution and incubate at room temperature in the dark for 20 minutes;

[0064] Step 8: Add 50 μl 2M H2SO4 stop solution to each well. Measure the absorbance at 450 nm using an ELISA reader and calculate the content.

[0065] Hydroxyproline content determination, steps are:

[0066] Step 1: Weigh 30 mg of liver tissue, add 1 mL of hydrolysis solution, mix well, and hydrolyze in a boiling water bath for 20 minutes;

[0067] Step 2: After cooling, add 10 μl of indicator to each EP tube and shake well;

[0068] Step 3: Accurately add 1.0 mL of the pH adjustment kit's own solution A to each ep tube and mix well;

[0069] Step 4: Take the pH adjustment solution provided by the kit and carefully add the pH adjustment solution drop by drop to each ep tube. Mix well after adding drop by drop until the color of the indicator in the liquid turns yellow-green. At this time, the pH value is between 6.0 and 6.8.

[0070] Step 5: Add double distilled water to 10 mL and mix well;

[0071] Step 6: Take 3-4 mL of the diluted hydrolyzate and add 25 mg of activated carbon, mix well, centrifuge at 3500 rpm for 10 minutes, and carefully take 1 mL of the supernatant for detection;

[0072] Step 7: Add 0.5mL of reagents 1, 2, and 3 in the kit in sequence according to the kit operation table;

[0073] Step 8: Mix well, place in a water bath at 60 degrees for 15 minutes, cool, and centrifuge at 3500 rpm for 10 minutes;

[0074] Step 9: Take the supernatant and detect the absorbance of each tube at a wavelength of 550nm, and calculate the content according to the instructions.

[0075] Embodiment 1:

[0076] This application investigates the single protective effects of dihydromyricetin and smilax glabra saponin on metabolism-related fatty liver disease.

[0077] Establishment of animal model of metabolic-related fatty liver disease: 12-month-old male low-density lipoprotein receptor knockout (LDLr - / - ) mice were fed a high-fat diet (HFD, containing 21% fat and 0.21% cholesterol) for 12 weeks to establish a mouse model of metabolic-related fatty liver disease.

[0078] The modeling mice were randomly divided into 4 groups: model group (HFD group), low-dose dihydromyricetin group (100 mg / kg / dayDMY), medium-dose group (200 mg / kg / dayDMY), high-dose group (400 mg / kg / dayDMY), low-dose sarsaponin group (100 mg / kg / day Par), medium-dose group (200 mg / kg / dayPar), and high-dose group (400 mg / kg / dayPar).

[0079] The drug intervention group was fed with high-fat diet and given corresponding drugs. At the same time, a normal control group was set up, which was 12-month-old male LDLr - / - Mice. 8 mice in each group. After 12 weeks, the serum glucose and insulin levels, serum total cholesterol (TC) content, triglyceride (TG) content, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of mice were detected; the TC and TG content in the liver was detected; the inflammatory factors TNF-α and IL-6 content in the liver was detected; and the hydroxyproline content in the liver was detected.

[0080] Table 1 Effects of dihydromyricetin and smilaxonin on metabolic parameters (mean±SD).

[0081]

[0082]

[0083] **Compared with the control group, P<0.01; #Compared with the HFD model group, P<0.05; ##Compared with the HFD model group, P<0.01; P<0.05 means there is a significant difference, and P<0.01 means there is a very significant difference.

[0084] The results are shown in Table 1. Dihydromyricetin alone had a significant improvement on serum metabolic parameters, and the improvement increased with the dose of dihydromyricetin. Smilax china saponin alone had no significant effect on serum metabolic parameters, and there was no significant difference compared with the model group.

[0085] Table 2 Effects of dihydromyricetin and sarsaponin on liver damage (mean ± SD):

[0086] Grouping AST(U / L) ALT (U / mL) Normal control group 37.38±4.11 51.58±9.79 HFD group <![CDATA[145.63±26.23 ** ]]> <![CDATA[171.08±21.14 ** ]]> HFD+100mg / kg / day DMY group <![CDATA[105.22±17.50 # ]]> <![CDATA[124.8±17.86 # ]]> HFD+200mg / kg / day DMY group <![CDATA[75.73±14.02 # ]]> <![CDATA[107.95±19.45 # ]]> HFD+400mg / kg / day DMY group <![CDATA[50.21±13.53 ## ]]> <![CDATA[60.26±14.8 ## ]]> HFD+100mg / kg / day Par group 141.84±25.54 168..66±18.35 HFD+200mg / kg / day Par group 139.5±21.75 160.5±19.32 HFD+400mg / kg / day Par group 135.95±20.88 154.25±23.57

[0087] **P<0.01 compared with the control group; #P<0.05 compared with the HFD model group; ##P<0.01 compared with the HFD model group. P<0.05 means there is a significant difference, and P<0.01 means there is a very significant difference.

[0088] The results are shown in Table 2. Dihydromyricetin alone can reduce the levels of ALT and AST, the liver damage markers in serum. With the increase of dihydromyricetin dose, the levels of serum ALT and AST decreased significantly. The single use of sarsaparilla saponin had no obvious effect on the levels of serum ALT and AST, and there was no significant difference compared with the model group.

[0089] Table 3 Effects of dihydromyricetin and sarsaponin on liver fatty degeneration (mean ± SD)

[0090]

[0091]

[0092] **P<0.01 compared with the control group; #P<0.05 compared with the HFD model group; ##P<0.01 compared with the HFD model group. P<0.05 means there is a significant difference, and P<0.01 means there is a very significant difference.

[0093] The results are shown in Table 3. Dihydromyricetin alone can reduce the content of TC and TG in the liver. With the increase of dihydromyricetin dose, the content of TC and TG in the liver decreased significantly. Smilax glabra saponin alone had no obvious effect on the content of TC and TG in the liver, and there was no significant difference compared with the model group.

[0094] Table 4 Effects of dihydromyricetin and sarsaponin on liver inflammation (mean ± SD)

[0095] Grouping TNF-α(pg / mg) IL-6 (pg / mg) Normal control group 515±109.90 967±147.69 HFD group <![CDATA[1172.25±185.32 ** ]]> <![CDATA[1929.13±222.70 ** ]]> HFD+100mg / kg / day DMY group 989.63±152.94 1777.38±292.88 HFD+200mg / kg / day DMY group <![CDATA[879.5±155.10 # ]]> <![CDATA[1459±270.67 # ]]> HFD+400mg / kg / day DMY group <![CDATA[603.75±135.76 ## ]]> <![CDATA[1262±255.74 ## ]]> HFD+100mg / kg / day Par group 1126.13±207.61 1886.75±311.88 HFD+200mg / kg / day Par group 1082±221.98 1802.88±368.87 HFD+400mg / kg / day Par group 1031.63±202.03 1765.63±390.02

[0096] **P<0.01 compared with the control group; #P<0.05 compared with the HFD model group; ##P<0.01 compared with the HFD model group. P<0.05 means there is a significant difference, and P<0.01 means there is a very significant difference.

[0097] The results are shown in Table 4. Dihydromyricetin alone can reduce the levels of inflammatory factors tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in the liver. With the increase of dihydromyricetin dose, the levels of TNF-α and IL-6 in the liver decreased significantly. The single use of sarsaponin had no obvious effect on the levels of TNF-α and IL-6 in the liver, and there was no significant difference compared with the model group.

[0098] Table 5 Effects of dihydromyricetin and sarsaponin on liver fibrosis (mean ± SD)

[0099]

[0100]

[0101] **P<0.01 compared with the control group; #P<0.05 compared with the HFD model group; ##P<0.01 compared with the HFD model group. P<0.05 means there is a significant difference, and P<0.01 means there is a very significant difference.

[0102] The results are shown in Table 5. Dihydromyricetin alone can reduce the content of hydroxyproline, a marker of collagen deposition in the liver. With the increase of dihydromyricetin dose, the content of hydroxyproline in the liver decreased significantly. The effect of sarsaparilla saponin alone on the content of hydroxyproline in the liver was not obvious, and there was no significant difference compared with the model group.

[0103] Embodiment 2:

[0104] The present application investigates the protective effect of a combination of dihydromyricetin and smilax china saponin on metabolism-related fatty liver disease.

[0105] The mice were divided into a normal control group, a model group (HFD group), a low-dose group (100 mg / kg / day DMY+50 mg / kg / dayPar), a medium-dose group (100 mg / kg / dayDMY+100 mg / kg / dayPar) and a high-dose group (100 mg / kg / dayDMY+200 mg / kg / dayPar) of the combination of dihydromyricetin and sarsaponin. The drug intervention group was given corresponding drugs while being fed with a high-fat diet. There were 8 mice in each group. After 12 weeks, the serum glucose and insulin levels, serum total cholesterol (TC) content, triglyceride (TG) content, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of the mice were detected; the TC and TG contents in the liver were detected; the inflammatory factors tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) contents in the liver were detected; and the hydroxyproline content in the liver was detected.

[0106] Table 6 Effects of dihydromyricetin combined with sarsaponin on metabolic parameters (mean ± SD)

[0107]

[0108]

[0109] **P<0.01 compared with the control group; #P<0.05 compared with the HFD model group; ##P<0.01 compared with the HFD model group. P<0.05 means there is a significant difference, and P<0.01 means there is a very significant difference.

[0110] The results are shown in Table 6. The combination of dihydromyricetin and sarsaponin has a significant improvement effect on serum metabolic parameters, and the metabolic parameter values ​​are significantly lower than those of the single dihydromyricetin drug group at the same dose (100 mg / kg / dayDMY). This shows that sarsaponin has a significant synergistic effect on the improvement of serum metabolic parameters of dihydromyricetin, and the synergistic effect gradually increases with the increase in the amount of sarsaponin used.

[0111] Table 7 Effects of dihydromyricetin combined with sarsaponin on liver damage (mean±SD)

[0112]

[0113] **P<0.01 compared with the control group; #P<0.05 compared with the HFD model group; ##P<0.01 compared with the HFD model group. P<0.05 means there is a significant difference, and P<0.01 means there is a very significant difference.

[0114] The results are shown in Table 7. The combination of dihydromyricetin and sarsaponin significantly reduced the levels of ALT and AST, the liver injury markers in serum, and the levels of ALT and AST were significantly lower than those of the single dihydromyricetin drug group at the same dose (100 mg / kg / dayDMY). This shows that sarsaponin has a significant synergistic effect on dihydromyricetin in inhibiting liver injury, and the synergistic effect gradually increases with the increase in the amount of sarsaponin used.

[0115] Table 8 Effects of dihydromyricetin combined with sarsaponin on liver fatty degeneration (mean ± SD)

[0116]

[0117]

[0118] **P<0.01 compared with the control group; #P<0.05 compared with the HFD model group; ##P<0.01 compared with the HFD model group. P<0.05 means there is a significant difference, and P<0.01 means there is a very significant difference.

[0119] The results are shown in Table 8. The combination of dihydromyricetin and sarsaponin significantly reduced the TC and TG contents in the liver, and the TC and TG contents were significantly lower than those of the single dihydromyricetin drug group at the same dose (100 mg / kg / dayDMY). This shows that sarsaponin has a significant synergistic effect on the inhibitory effect of dihydromyricetin on liver fatty degeneration, and the synergistic effect gradually increases with the increase in the dosage of sarsaponin.

[0120] Table 9 Effects of dihydromyricetin combined with sarsaponin on liver inflammation (mean ± SD)

[0121]

[0122] **P<0.01 compared with the control group; #P<0.05 compared with the HFD model group; ##P<0.01 compared with the HFD model group. P<0.05 means there is a significant difference, and P<0.01 means there is a very significant difference.

[0123] The results are shown in Table 9. The combination of dihydromyricetin and sarsaponin significantly reduced the levels of inflammatory factors tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in the liver, and the levels of TNF-α and IL-6 were significantly lower than those of the single dihydromyricetin drug group at the same dose (100 mg / kg / dayDMY). This shows that sarsaponin has a significant synergistic effect on the inhibition of liver inflammation by dihydromyricetin, and the synergistic effect gradually increases with the increase in the amount of sarsaponin used.

[0124] Table 10 Effects of dihydromyricetin combined with sarsaponin on liver fibrosis (mean ± SD)

[0125] Grouping Hydroxyproline (μg / mg) Normal control group 0.165±0.029 HFD group <![CDATA[0.541±0.087 ** ]]> HFD+100mg / kg / day DMY+50mg / kg / day Par group 0.405±0.062 HFD+100mg / kg / day DMY+100mg / kg / day Par group <![CDATA[0.332±0.076 # ]]> HFD+100mg / kg / day DMY+200mg / kg / day Par group <![CDATA[0.234±0.042 ## ]]>

[0126] **P<0.01 compared with the control group; #P<0.05 compared with the HFD model group; ##P<0.01 compared with the HFD model group. P<0.05 means there is a significant difference, and P<0.01 means there is a very significant difference.

[0127] The results are shown in Table 10. The combination of dihydromyricetin and sarsaponin significantly reduced the content of hydroxyproline, a marker of liver collagen deposition, and the hydroxyproline content was significantly lower than that of the single dihydromyricetin drug group at the same dose (100 mg / kg / day DMY). This shows that sarsaponin has a significant synergistic effect on the inhibitory effect of dihydromyricetin on liver fibrosis, and the synergistic effect gradually increases with the increase in the amount of sarsaponin used.

[0128] The above is only a preferred specific implementation manner of the present invention, and the protection scope of the present invention is not limited thereto. Any simple change or equivalent replacement of the technical solution that can be obviously obtained by any technician familiar with the technical field within the technical scope disclosed in the present invention falls within the protection scope of the present invention.

Claims

1. The use of sarsaparilla saponin in the preparation of a synergist for dihydromyricetin against metabolic-related fatty liver disease, characterized in that: Smilax china saponin is used as a synergist against metabolic-related fatty liver disease and is used in combination with dihydromyricetin to form a pharmaceutical composition for synergistically resisting metabolic-related fatty liver disease. The structural formula of the smilax china saponin is 。 2. A pharmaceutical composition for preventing or treating metabolic-related fatty liver disease, characterized in that: The active ingredients of the pharmaceutical composition are composed of dihydromyricetin and smilaxonin, the weight ratio of dihydromyricetin to smilaxonin is 1:0.5-2, and the structural formula of smilaxonin is 。 3. The pharmaceutical composition according to claim 2, characterized in that: The weight ratio of the dihydromyricetin to smilaxonin is 1:

1.

4. The pharmaceutical composition according to claim 2, characterized in that: The metabolism-related fatty liver disease is metabolism-related fatty liver hepatitis.

5. The pharmaceutical composition according to claim 2, characterized in that: The pharmaceutical composition also contains pharmaceutically acceptable excipients.

6. The pharmaceutical composition according to claim 2, characterized in that: The pharmaceutical composition is administered orally or parenterally.

7. The pharmaceutical composition according to claim 6, characterized in that: The oral or non-oral administration is specifically by subcutaneous injection, intramuscular injection, intravenous injection, oral administration, rectal administration or nasal administration.

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