A pharmaceutical composition and its use in the preparation of a medicament for treating acute liver injury

Abstract

The application discloses a kind of pharmaceutical composition and its application in preparation treatment acute liver injury drug, it is related to natural medicine and biomedical technical field.The pharmaceutical composition of the application includes the mass ratio of 3~7:1~5:0.5~3.5 compound A, compound B and compound C, and the CAS of compound A, compound B and compound C is 2199455-72-4, 21074-63-5 and 453518-30-4 respectively;The application also provides the application of the pharmaceutical composition in preparation treatment acute liver injury drug.The application is screened by natural active ingredient in Pseuderugia fortunei Maxim, and it is found that the pharmaceutical composition of compound A, compound B and compound C derived from Pseuderugia fortunei extract can significantly improve acute liver injury, reduce liver tissue inflammatory response and improve animal survival rate, and has higher safety, is suitable for development as natural medicine for treating acute liver injury.

Description

Technical Field

[0001] This invention relates to the fields of natural medicines and biomedicine, specifically to a pharmaceutical composition and its application in the preparation of a drug for treating acute liver injury. Background Technology

[0002] Acute liver injury (ALI) is a serious liver disease induced by various factors such as drugs, viral infections, alcohol, toxins, and immune abnormalities. Its main characteristics include hepatocellular necrosis, the release of large amounts of inflammatory factors, and a rapid decline in liver function. In severe cases, it can further develop into acute liver failure, with a high mortality rate. Currently, the types of drugs available for the clinical treatment of ALI are limited, and they suffer from unstable efficacy and significant side effects. Therefore, the development of safe and effective novel drugs for treating acute liver injury is of great importance.

[0003] Natural medicines have gained widespread attention in the treatment of liver diseases due to their multi-target effects, low toxicity, and good biocompatibility. One such medicine is *Corydalis fulva*, a plant in the Asteraceae family. Soroseris hookeriana It contains abundant sesquiterpene lactones, flavonoids, and phenolic acids, which possess anti-inflammatory, antioxidant, and immunomodulatory biological activities. However, systematic research on the combined use of multiple components derived from *Cressella fuciformis* for the treatment of acute liver injury is currently lacking. Summary of the Invention

[0004] The purpose of this invention is to at least solve one of the technical problems existing in the prior art, and to provide a pharmaceutical composition and its application in the preparation of a drug for treating acute liver injury. The pharmaceutical composition is derived from *Senna tora* extract and has the effect of significantly reducing liver tissue inflammation and damage, improving liver function and increasing survival rate.

[0005] This invention, through screening natural active ingredients in *Sedum curvatureum*, discovered that the combined use of compounds A (CAS No.: 2199455-72-4), B (CAS No.: 21074-63-5), and C (CAS No.: 453518-30-4) derived from *Sedum curvatureum* extract significantly alleviated LPS / D-GalN-induced acute liver injury in mice. It significantly improved acute liver injury, reduced liver tissue inflammation, and increased animal survival rates, exhibiting a synergistic therapeutic effect significantly superior to that of a single component, thus completing this invention.

[0006] The technical solution of the present invention is as follows: In a first aspect, the present invention provides a pharmaceutical composition comprising compound A, compound B and compound C; The compound A is named Prionidipene A, with CAS number 2199455-72-4 and molecular formula C. 21 H 26 O3, structural formula is ; The compound B is named dihydropiperine, with CAS number 21074-63-5 and molecular formula C. 14 H 14 O3, structural formula is ; The Chinese name of compound C is (9AS)-7,8,9,9A-tetrahydro-9A-hydroxy-6-methyl-9-(1-methylvinyl)-2-(1-methylethyl)-1H-naphthalene-1-one, CAS number is 453518-30-4, and molecular formula is C 20 H 24 O2, structural formula is ; The mass ratio of compound A, compound B and compound C is 3~7:1~5:0.5~3.5.

[0007] In a preferred embodiment of the present invention, the mass ratio of compound A, compound B and compound C is 4~7:2~4:1~3.

[0008] In a preferred embodiment of the present invention, the mass ratio of compound A, compound B and compound C is 5:3:2 or 7:3:2 or 5:5:2.

[0009] In a preferred embodiment of the present invention, the pharmaceutical composition may be prepared into a pharmaceutically acceptable dosage form, including but not limited to injections, tablets, capsules, granules, lyophilized powder for injection, or oral liquid.

[0010] Secondly, the present invention provides the use of the pharmaceutical composition described herein in the preparation of a medicament for treating acute liver injury.

[0011] In a preferred embodiment of the present invention, the acute liver injury is at least one of a drug for treating drug-induced liver injury, a drug for treating viral hepatitis, a drug for treating ischemic liver injury, and a drug for treating autoimmune hepatitis.

[0012] In a preferred embodiment of the present invention, an LPS / D-GalN-induced inflammatory liver injury model is used to simulate acute liver failure.

[0013] In a preferred embodiment of the present invention, the drug is a drug that inhibits the expression of inflammatory factors in liver tissue and / or improves liver function damage.

[0014] In a preferred embodiment of the present invention, the drug inhibits the expression of inflammatory factors in liver tissue by reducing TNF-α and / or IL-1β levels.

[0015] In a preferred embodiment of the present invention, the drug improves liver function impairment by reducing AST and / or ALT levels.

[0016] Thirdly, the present invention provides a medicament for treating acute liver injury, comprising the aforementioned pharmaceutical composition and a pharmaceutically acceptable carrier.

[0017] In a preferred embodiment of the present invention, the dosage of the pharmaceutical composition is 10 mg / kg to 20 mg / kg.

[0018] In a preferred embodiment of the present invention, the pharmaceutically acceptable carrier includes at least one of a solvent, a dispersion medium, an isotonicity modifier, and an adjuvant.

[0019] In a preferred embodiment of the present invention, the solvent is water, glycerol, or ethanol.

[0020] In a preferred embodiment of the present invention, the dispersion medium is water, ethanol or sugar.

[0021] In a preferred embodiment of the present invention, the isotonic regulator is distilled water, glucose, polyol or sodium chloride.

[0022] In a preferred embodiment of the present invention, the additive is an emulsifier, preservative, solubilizer, or stabilizer.

[0023] This invention has at least one of the following beneficial effects: 1. The pharmaceutical composition of the present invention can significantly improve the survival rate of mice with acute liver injury; 2. The pharmaceutical composition of the present invention can significantly reduce liver tissue necrosis and inflammatory infiltration; 3. The pharmaceutical composition of the present invention can significantly reduce serum ALT and AST levels; 4. The pharmaceutical composition of the present invention can inhibit the release of inflammatory factors TNF-α and IL-1β; Therefore, the pharmaceutical composition of the present invention can be used to prepare a drug for treating acute liver injury. Moreover, compared with a single compound, the combined use of the three natural compounds in the present invention has a significant synergistic effect, high safety, and is suitable for development into a natural drug for treating acute liver injury. Attached Figure Description

[0024] Figure 1 The figure shows the effect of each group in Test Example 1 on the survival rate of mice with LPS / D-GalN-induced acute liver injury. Figure 2The images show the pathological results of H&E staining of liver tissue from each group of mice in Test Example 2. Figure 3 The figure shows the results of the effects of test example 2 on inflammatory factors and liver function indicators in mice with acute liver injury. Detailed Implementation

[0025] To make the technical problems solved, the technical solutions, and the beneficial effects of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0026] Compound A was purchased from MedChemExpress, catalog number HY-N13755.

[0027] Compound B was purchased from MedChemExpress, catalog number HY-N19680.

[0028] Compound C was purchased from MedChemExpress, catalog number HY-N1316.

[0029] Example 1 A pharmaceutical composition comprising compound A (CAS No.: 2199455-72-4), compound B (CAS No.: 21074-63-5) and compound C (CAS No.: 453518-30-4), wherein the mass ratio of compound A, compound B and compound C is 5:3:2.

[0030] Comparative Example 1 The difference from Example 1 is that it does not include compounds C and B, but only includes compound A.

[0031] Comparative Example 2 The difference from Example 1 is that it does not include compounds C and A, but only includes compound B.

[0032] Comparative Example 3 The difference from Example 1 is that it does not include compounds A and B, but only includes compound C.

[0033] Comparative Example 4 The difference from Example 1 is that it does not include compound C, but only includes compound A and compound B, with the same mass ratio as in Example 1.

[0034] Comparative Example 5 The difference from Example 1 is that it does not include compound B, but only includes compound A and compound C, with the same mass ratio as in Example 1.

[0035] Comparative Example 6 The difference from Example 1 is that it does not include compound A, but only includes compounds B and C, with the same mass ratio as in Example 1.

[0036] Comparative Example 7 The difference from Example 1 is that NAC (N-acetyl-L-cysteine) is used as the positive therapeutic agent.

[0037] Example 2 The difference from Example 1 is that the amount of compound A is reduced, that is, the mass ratio of compound A, compound B and compound C is 3:3:2.

[0038] Example 3 The difference from Example 1 is that the amount of compound A is increased, that is, the mass ratio of compound A, compound B and compound C is 7:3:2.

[0039] Example 4 The difference from Example 1 is that the amount of compound B is reduced, that is, the mass ratio of compound A, compound B and compound C is 5:1:2.

[0040] Example 5 The difference from Example 1 is that the amount of compound B is increased, that is, the mass ratio of compound A, compound B and compound C is 5:5:2.

[0041] Example 6 The difference from Example 1 is that the amount of compound C is reduced, that is, the mass ratio of compound A, compound B and compound C is 5:3:0.5.

[0042] Example 7 The difference from Example 1 is that the amount of compound C is increased, that is, the mass ratio of compound A, compound B and compound C is 5:3:3.5.

[0043] Test Example 1: Effect of the drug composition on the survival rate of mice with acute liver injury The pharmaceutical compositions prepared in Examples 1-7 and the drugs in Comparative Examples 1-7 were used to feed mice with acute liver injury to demonstrate the effect of the above drugs on the survival rate of mice with acute liver injury. The specific methods are as follows: 1. Laboratory animals Male BALB / c mice were selected and used in the experiment after one week of acclimatization.

[0044] 2. Reagent Preparation LPS (lipopolysaccharide) was prepared into a 2 mg / mL stock solution using physiological saline; D-GalN (D-galactosamine) was prepared into a 200 mg / mL stock solution using physiological saline; compounds A, B, and C were each prepared into a 5 mg / mL stock solution using physiological saline, or into a 10 mg / mL stock solution using physiological saline at a mass ratio of 5:3:2; NAC was prepared into a 50 mg / mL stock solution using physiological saline.

[0045] 2. Modeling and Drug Delivery The mice were divided into 17 groups of 10 mice each, as follows: 1. Control group: Intraperitoneal injection and gavage administration of an equal volume of physiological saline; 2. LPS / D-GalN group (model group): intraperitoneal injection of 1.5 mg / kg LPS and 800 mg / kg D-GalN; 3. LPS / D-GalN + low-dose group (Example 1): 1.5 mg / kg LPS and 800 mg / kg D-GalN were administered intraperitoneally, while 10 mg / kg of the composition in Example 1 was administered by gavage. 4. LPS / D-GalN + high-dose group (Example 1): 1.5 mg / kg LPS and 800 mg / kg D-GalN were injected intraperitoneally, while 20 mg / kg of the composition in Example 1 was administered by gavage. 5. LPS / D-GalN + Compound A group (Comparative Example 1): 1.5 mg / kg LPS and 800 mg / kg D-GalN were administered intraperitoneally, while 10 mg / kg compound A was administered by gavage. 6. LPS / D-GalN+compound B group (comparative example 2): 1.5 mg / kg LPS and 800 mg / kg D-GalN were administered intraperitoneally, while 6 mg / kg compound B was administered by gavage. 7. LPS / D-GalN + Compound C group (Comparative Example 3): 1.5 mg / kg LPS and 800 mg / kg D-GalN were administered intraperitoneally, while 4 mg / kg compound C was administered by gavage. 8. LPS / D-GalN+compound A+B group (comparative example 4): 1.5 mg / kg LPS and 800 mg / kg D-GalN were administered intraperitoneally, while 10 mg / kg compound A and 6 mg / kg compound B were administered by gavage. 9. LPS / D-GalN+compound A+C group (comparative example 5): 1.5 mg / kg LPS and 800 mg / kg D-GalN were administered intraperitoneally, while 10 mg / kg compound A and 4 mg / kg compound C were administered by gavage. 10. LPS / D-GalN+compound B+C group (comparative example 6): 1.5 mg / kg LPS and 800 mg / kg D-GalN were administered intraperitoneally, while 6 mg / kg compound B and 4 mg / kg compound C were administered by gavage. 11. LPS / D-GalN + Compound A (low) + B + C group (Example 2): 1.5 mg / kg LPS and 800 mg / kg D-GalN were injected intraperitoneally, while 6 mg / kg compound A, 6 mg / kg compound B and 4 mg / kg compound C were administered by gavage. 12. LPS / D-GalN + Compound A (high) + B + C group (Example 3): 1.5 mg / kg LPS and 800 mg / kg D-GalN were injected intraperitoneally, while 14 mg / kg compound A, 6 mg / kg compound B and 4 mg / kg compound C were administered by gavage. 13. LPS / D-GalN + Compound A + B (low) + C group (Example 4): 1.5 mg / kg LPS and 800 mg / kg D-GalN were injected intraperitoneally, while 10 mg / kg compound A, 2 mg / kg compound B and 4 mg / kg compound C were administered by gavage. 14. LPS / D-GalN + Compound A + B (high) + C group (Example 5): 1.5 mg / kg LPS and 800 mg / kg D-GalN were injected intraperitoneally, while 10 mg / kg compound A, 10 mg / kg compound B and 4 mg / kg compound C were administered by gavage. 15. LPS / D-GalN+compound A+B+C (low) group (Example 6): 1.5 mg / kg LPS and 800 mg / kg D-GalN were injected intraperitoneally, while 10 mg / kg compound A, 6 mg / kg compound B and 1 mg / kg compound C were administered by gavage. 16. LPS / D-GalN+compound A+B+C (high) group (Example 7): 1.5 mg / kg LPS and 800 mg / kg D-GalN were injected intraperitoneally, while 6 mg / kg compound A, 6 mg / kg compound B and 7 mg / kg compound C were administered by gavage. 17. LPS / D-GalN+NAC group (Comparative Example 7): Intraperitoneal injection of 1.5 mg / kg LPS and 800 mg / kg D-GalN, and intraperitoneal injection of 100 mg / kg NAC.

[0046] The number of dead mice was counted every 3 hours, and the survival rate of the mice was monitored until 24 hours after LPS / D-GalN injection.

[0047] 3. Experimental Results The results are as follows Figure 1 As shown, 24 hours after LPS / D-GalN injection, the survival rate was 100% in the control group, 10% in the LPS / D-GalN model group, 60% in the LPS / D-GalN + low-dose group, 90% in the LPS / D-GalN + high-dose group, 40% in the LPS / D-GalN + compound A group, 40% in the LPS / D-GalN + compound B group, 30% in the LPS / D-GalN + compound C group, 50% in the LPS / D-GalN + compound A + B group, and 50% in the LPS / D-GalN + compound A + C group. The survival rate of the LPS / D-GalN+ compound B+C group was 40%, the survival rate of the LPS / D-GalN+ compound A (low) + B+C group was 80%, the survival rate of the LPS / D-GalN+ compound A (high) + B+C group was 90%, the survival rate of the LPS / D-GalN+ compound A+B (low) + C group was 70%, the survival rate of the LPS / D-GalN+ compound A+B (high) + C group was 90%, the survival rate of the LPS / D-GalN+ compound A+B+C (low) group was 80%, the survival rate of the LPS / D-GalN+ compound A+B+C (high) group was 80%, and the survival rate of the LPS / D-GalN+NAC group was 50%.

[0048] As shown in Table 1, the Kaplan-Meier survival analysis results indicate that, compared with the LPS / D-GalN group, the survival rate of mice treated with the drug composition in Example 1 was significantly improved in both the low-dose LPS / D-GalN+ group and the high-dose LPS / D-GalN+ group. p <0.05); and the survival rate of mice in the high-dose group was significantly higher than that in the positive treatment drug NAC group ( p <0.05%, indicating that the pharmaceutical composition of the present invention can effectively improve the survival rate of mice with acute liver injury. Compared with Comparative Examples 1 to 6, the survival rate of mice treated with the pharmaceutical composition in Example 1 was significantly higher than that of mice fed alone with compound A, compound B, compound C, or compound A+B, compound A+C, or compound B+C.p <0.05), therefore, compared with a single compound or a combination of two compounds, the combined application of the three compounds in this invention has a significant synergistic effect. Compared with the LPS / D-GalN group, the survival rate of mice treated with the drug compositions in Examples 2 to 7 was significantly improved ( p The value <0.05 indicates that when compounds A, B, and C are in a mass ratio range of 3~7:1~5:0.5~3.5, the combination of compounds A, B, and C can effectively improve the survival rate of mice with acute liver injury.

[0049] Table 1. Kaplan-Meier survival analysis results of LPS / D-GalN-induced acute liver injury mice in each group. Test Example 2: Effect of the drug composition on pathological damage to liver tissue Mice with acute liver injury were fed with the pharmaceutical compositions prepared in Examples 1-7 and the drugs in Comparative Examples 1-7, and the pathological damage of the mouse liver tissue was detected. The specific methods are as follows: 1. Laboratory animals Male BALB / c mice were selected and used in the experiment after one week of acclimatization.

[0050] 2. Reagent Preparation LPS was prepared into a 1 mg / mL stock solution using physiological saline; D-GalN was prepared into a 200 mg / mL stock solution using physiological saline; and compounds A, B, and C were prepared into a 10 mg / mL stock solution using physiological saline in a mass ratio of 5:3:2.

[0051] 3. Modeling and Drug Delivery The mice were divided into 17 groups, with 6 mice in each group. The experimental groups are as follows: 1. Control group: Intraperitoneal injection and gavage administration of an equal volume of physiological saline; 2. LPS / D-GalN group (model group): intraperitoneal injection of 0.1 mg / kg LPS and 400 mg / kg D-GalN; 3. LPS / D-GalN + low-dose group (Example 1): 0.1 mg / kg LPS and 400 mg / kg D-GalN were administered intraperitoneally, while 10 mg / kg of the composition in Example 1 was administered by gavage. 4. LPS / D-GalN + high-dose group (Example 1): 0.1 mg / kg LPS and 400 mg / kg D-GalN were administered intraperitoneally, while 20 mg / kg of the composition in Example 1 was administered by gavage. 5. LPS / D-GalN + Compound A group (Comparative Example 1): 0.1 mg / kg LPS and 400 mg / kg D-GalN were administered intraperitoneally, while 10 mg / kg compound A was administered by gavage. 6. LPS / D-GalN+compound B group (comparative example 2): 0.1 mg / kg LPS and 400 mg / kg D-GalN were administered intraperitoneally, while 6 mg / kg compound B was administered by gavage. 7. LPS / D-GalN+compound C group (comparative example 3): 0.1 mg / kg LPS and 400 mg / kg D-GalN were administered intraperitoneally, while 4 mg / kg compound C was administered by gavage. 8. LPS / D-GalN + Compound A + B group (Comparative Example 4): 0.1 mg / kg LPS and 400 mg / kg D-GalN were administered intraperitoneally, while 10 mg / kg compound A and 6 mg / kg compound B were administered by gavage. 9. LPS / D-GalN+compound A+C group (comparative example 5): 0.1 mg / kg LPS and 400 mg / kg D-GalN were administered intraperitoneally, while 10 mg / kg compound A and 4 mg / kg compound C were administered by gavage. 10. LPS / D-GalN+compound B+C group (comparative example 6): 0.1 mg / kg LPS and 400 mg / kg D-GalN were administered intraperitoneally, while 6 mg / kg compound B and 4 mg / kg compound C were administered by gavage. 11. LPS / D-GalN+compound A (low) + B+C group (Example 2): 0.1 mg / kg LPS and 400 mg / kg LPS were administered intraperitoneally, while 6 mg / kg compound A, 6 mg / kg compound B and 4 mg / kg compound C were administered by gavage. 12. LPS / D-GalN+ compound A (high) + B+C group (Example 3): 0.1 mg / kg LPS and 400 mg / kg LPS were administered intraperitoneally, while compound A (14 mg / kg), compound B (6 mg / kg), and compound C (4 mg / kg) were administered by gavage. 13. LPS / D-GalN+ compound A+B (low)+C group (Example 4): 0.1 mg / kg LPS and 400 mg / kg LPS were administered intraperitoneally, while 10 mg / kg compound A, 2 mg / kg compound B and 4 mg / kg compound C were administered by gavage. 14. LPS / D-GalN+ compound A+B (high)+C group (Example 5): 0.1 mg / kg LPS and 400 mg / kg LPS were administered intraperitoneally, while 10 mg / kg compound A, 10 mg / kg compound B and 4 mg / kg compound C were administered by gavage. 15. LPS / D-GalN+compound A+B+C (low) group (Example 6): 0.1 mg / kg LPS and 400 mg / kg D-GalN were administered intraperitoneally, while 10 mg / kg compound A, 6 mg / kg compound B and 1 mg / kg compound C were administered by gavage. 16. LPS / D-GalN+ compound A+B+C (high) group (Example 7): 0.1 mg / kg LPS and 400 mg / kg LPS were administered intraperitoneally, while 6 mg / kg compound A, 6 mg / kg compound B and 7 mg / kg compound C were administered by gavage. 17. LPS / D-GalN+NAC group (Comparative Example 7): 0.1 mg / kg LPS and 400 mg / kg D-GalN were administered intraperitoneally, along with 100 mg / kg NAC administered intraperitoneally.

[0052] Twelve hours after drug administration, all mice were sacrificed and liver tissue was collected. The liver tissue was fixed in 4% paraformaldehyde and embedded in paraffin. The tissue was cut into 5 μm thick sections, and sections were stained with H&E to assess histopathological changes in the liver tissue. The results are as follows Figure 2 As shown, the liver tissue structure of the control group was intact; the LPS / D-GalN group showed obvious sinusoidal congestion, focal necrosis, inflammatory cell infiltration, and tissue structure destruction. Compared with the LPS / D-GalN group, treatment with the drug compositions prepared in Examples 1 to 7 significantly reduced liver tissue damage, with the LPS / D-GalN + high-dose group showing the most significant improvement. Treatment with the drugs in Comparative Examples 1 to 7 also reduced liver tissue damage to some extent, but the degree of reduction was not as great as in Examples 1 to 7. Furthermore, compared with the positive therapeutic drug N-acetyl-L-cysteine, the drug compositions prepared in Examples 1 to 7 showed better liver tissue damage reduction.

[0053] The results showed that the pharmaceutical composition of the present invention could significantly reduce the pathological damage caused by acute liver injury; and, compared with the use of a single compound or two compounds, the three compounds of the present invention were more effective in reducing acute liver injury, indicating that the combined use of the three natural compounds in the present invention had a significant synergistic effect; in addition, the therapeutic effect of the pharmaceutical composition of the present invention was better than that of the positive control drug N-acetyl-L-cysteine.

[0054] Test Example 3: Effects of the drug composition on inflammatory factors and liver function indicators Blood was collected from each group of mice in test example 2. Serum was collected by centrifugation at 3000 rpm for 10 minutes at 4℃. The levels of TNF-α, IL-1β, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were detected using a kit.

[0055] The results are as follows Figure 3 As shown, compared with the LPS / D-GalN model group, treatment with the drug compositions prepared in Examples 1 to 7 significantly reduced the levels of AST, ALT, IL-1β, and TNF-α, with the most significant decreases observed in the high-dose LPS / D-GalN+ group. Treatment with the drugs in Comparative Examples 1 to 7 also resulted in some reductions in AST, ALT, IL-1β, and TNF-α levels, but the reductions were not as pronounced as in Examples 1 to 7. Furthermore, compared with the positive control drug N-acetyl-L-cysteine, treatment with the drug compositions prepared in Examples 1 to 7 resulted in a greater decrease in AST, ALT, IL-1β, and TNF-α levels.

[0056] The above results demonstrate that the pharmaceutical composition of the present invention can effectively inhibit inflammatory responses and improve liver function damage. Furthermore, compared with the use of a single or two compounds, the three compounds of the present invention show better effects in reducing AST, ALT, IL-1β, and TNF-α, indicating that the combined application of the three natural compounds in the present invention has a significant synergistic effect. In addition, the improvement effects in Examples 1-7 are superior to the LPS / D-GalN+NAC group, meaning that the pharmaceutical composition of the present invention has better anti-inflammatory and liver function improvement effects than the positive control drug N-acetyl-L-cysteine.

[0057] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A pharmaceutical composition, characterized in that, The pharmaceutical composition includes compound A, compound B, and compound C; The CAS number of compound A is 2199455-72-4; The CAS number of compound B is 21074-63-5; The CAS number of compound C is 453518-30-4; The mass ratio of compound A, compound B and compound C is 3~7:1~5:0.5~3.

5.

2. The pharmaceutical composition according to claim 1, characterized in that, The mass ratio of compound A, compound B and compound C is 4~7:2~4:1~3.

3. The pharmaceutical composition according to claim 1, characterized in that, The mass ratio of compound A, compound B and compound C is 5:3:2 or 7:3:2 or 5:5:

2.

4. Use of the pharmaceutical composition according to any one of claims 1 to 3 in the preparation of a medicament for treating acute liver injury.

5. The application according to claim 4, characterized in that, The drug is at least one of the following: drugs for treating drug-induced liver injury, drugs for viral hepatitis, drugs for ischemic liver injury, and drugs for autoimmune hepatitis.

6. The application according to claim 4, characterized in that, The drug is one that inhibits the expression of inflammatory factors in liver tissue and / or improves liver function.

7. The application according to claim 6, characterized in that, The drug inhibits the expression of inflammatory factors in liver tissue by reducing TNF-α and / or IL-1β levels.

8. The application according to claim 6, characterized in that, The drug improves liver function by lowering AST and / or ALT levels.

9. A drug for treating acute liver injury, characterized in that, The medicament for treating acute liver injury includes the pharmaceutical composition according to any one of claims 1 to 3 and a pharmaceutically acceptable carrier.

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