Application of compound ZML1 in preparation of medicine for treating acute drug-induced liver injury

Abstract

The invention discloses an application of a compound ZML1 in preparation of drugs for treating acute drug-induced liver injury. In-vivo and in-vitro experiments show that the ZML1 can reverse acute liver injury after acting for several hours, for example, the ZML1 can recover the normal form of liver cells, reduce lipid deposition, quickly improve the injury performance of various transaminases and the like. The treatment effect of the compound ZML1 on various liver injury indexes is superior to that of the existing liver protection medicine, and particularly, the compound ZML1 has a more excellent curative effect in the aspect of improving liver cell lipid deposition. Therefore, the ZML1 has excellent druggability in the aspects of treating acute drug-induced liver injury, protecting liver and the like, and further has a wide application prospect.

Description

Technical Field

[0001] The invention belongs to the technical field of natural medicines, and particularly relates to application of a compound ZML1 in preparing a medicine for treating acute drug-induced liver injury. Background Art

[0002] Diagnostic indicators of drug-induced liver injury (DILI) include: serum alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (ULN); alkaline phosphatase (ALP) ≥ 2 × ULN (especially when accompanied by elevated γ-glutamyl transpeptidase or when primary bone pathology is excluded); ALT ≥ 3 × ULN and total bilirubin (TB) > 2 × ULN. In addition, after drug withdrawal, liver function indicators improve; occasional re-administration of the drug rapidly stimulates liver damage; liver function tests are important clues for diagnosing DILI.

[0003] The basic treatment principles of DILI include timely discontinuation of suspected liver-injury drugs and avoiding the re-use of suspected or similar drugs as much as possible; fully weighing the risks of progression of the primary disease caused by discontinuation of the drug and worsening liver damage caused by continued use of the drug; selecting appropriate drug treatment according to the clinical type of DILI; and considering emergency liver transplantation for severe patients with acute liver failure / subacute liver failure when necessary.

[0004] At present, N-acetylcysteine ​​can be used for treatment of severe patients, early acute liver failure, and intrinsic DILI caused by acetaminophen; magnesium isoglycyrrhizinate can be used for treatment of acute hepatocellular injury or mixed DILI; glucocorticoids can be used for treatment of patients with obvious signs of hypersensitivity or autoimmunity, and whose biochemical indicators do not improve significantly or continue to deteriorate after discontinuation of liver injury drugs; ursodeoxycholic acid and adenosine methionine can be used for treatment of cholestatic DILI; silymarin can be used for treatment of mild to moderate hepatocellular injury and mixed DILI, and bicyclol and glycyrrhizic acid preparations can be used for treatment of patients with mild inflammation. However, the current treatment of these drugs is mainly symptomatic treatment, which is slow to take effect, has poor therapeutic effect on lipid deposition in the liver, and is difficult to reverse damage to liver tissue and cells. Therefore, it is urgent to develop a drug that can effectively improve lipid deposition in the liver and reverse damage to liver tissue and cells. Summary of the invention

[0005] In order to solve at least some of the technical problems in the above-mentioned prior art, the present invention provides the use of compound ZML1 in preparing a drug for treating acute drug-induced liver injury. Specifically, the present invention includes the following contents.

[0006] In a first aspect of the present invention, there is provided a use of a compound ZML1 in the preparation of a drug for preventing or treating acute drug-induced liver injury, wherein the compound ZML1 has a structure shown in Formula I:

[0007]

[0008] In certain embodiments, the compound ZML1 according to the present invention is used in the preparation of a drug for preventing or treating acute drug-induced liver injury, wherein the acute drug-induced liver injury includes liver injury caused by prescription or over-the-counter chemical drugs, biological preparations, natural medicines, health products and / or excipients.

[0009] In certain embodiments, the use of the compound ZML1 according to the present invention in the preparation of a drug for preventing or treating acute drug-induced liver injury, wherein the prevention or treatment comprises at least one of the following:

[0011] (1) Reduce or restore the amount of serum alanine aminotransferase;

[0012] (2) reduce or restore the amount of serum aspartate aminotransferase;

[0013] (3) Increase or restore the amount of total superoxide dismutase in liver tissue;

[0014] (4) Reduce swelling and inflammation of liver tissue;

[0015] (5) Reduce liver parenchymal lesions;

[0016] (6) Reduce lipid deposition;

[0017] (7) Promote liver damage repair;

[0018] (8) restore or protect liver cell morphology or function;

[0019] (9) Restore or protect liver function.

[0020] In certain embodiments, the compound ZML1 according to the present invention is used in the preparation of a drug for preventing or treating acute drug-induced liver injury, wherein the prevention or treatment is achieved by administering a therapeutically effective amount of the compound ZML1 to a subject.

[0021] In certain embodiments, according to the use of the compound ZML1 according to the present invention in the preparation of a medicament for preventing or treating acute drug-induced liver injury, wherein the effective amount is 1-1000 mg / kg.

[0022] In certain embodiments, according to the use of the compound ZML1 according to the present invention in the preparation of a medicament for preventing or treating acute drug-induced liver injury, the subject comprises a mammal.

[0023] The second aspect of the present invention provides a pharmaceutical composition for preventing or treating acute drug-induced liver injury, comprising compound ZML1 and a pharmaceutically acceptable carrier.

[0024] In certain embodiments, according to the pharmaceutical composition of the present invention, the pharmaceutically acceptable carrier comprises at least one of a diluent, a filler, an absorbent, a wetting agent, a binder, a disintegrant, a lubricant, a sweetener, a preservative and an antioxidant.

[0025] The third aspect of the present invention provides the use of the compound ZML1 in the preparation of a drug for treating acute drug-induced liver injury in combination with other drugs.

[0026] In certain embodiments, the compound ZML1 according to the present invention is used in the preparation of a drug for the combined treatment of acute drug-induced liver injury with other drugs, wherein the other drugs include at least one of ursodeoxycholic acid, N-acetylcysteine, magnesium isoglycyrrhizinate, glucocorticoids, adenosine methionine, silymarin, bicyclol, glycyrrhizic acid preparations, cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, tauroursodeoxycholic acid, hyodeoxycholic acid, taurocholic acid, glycocholic acid and arbidol hydrochloride.

[0027] The present invention has found through in vivo and in vitro experiments that ZML1 can reverse acute liver damage in just a few hours, such as restoring the normal morphology of liver cells, reducing lipid deposition, and rapidly improving the damage manifestations of various transaminases. After using ZML1 in an acute liver injury mouse model, various liver indicators were restored to near-normal levels compared with the injury group. The in vitro and in vivo experimental results of ZML1 were compared with the current "gold standard liver protection drug" ursodeoxycholic acid. The therapeutic effects of various damage indicators were better than ursodeoxycholic acid, especially in improving lipid deposition in liver cells. It showed a more excellent therapeutic effect. Therefore, ZML1 has excellent drugability in the treatment of acute drug-induced liver injury, protecting the liver, and so on, and thus has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It was shown that ZML1 can restore the functional impairment caused by acute drug-induced liver injury in vitro, wherein A showed that ZML1 can restore the decrease of aspartate aminotransferase (AST) in L-02 hepatocytes caused by acute drug-induced liver injury; B showed that ZML1 can restore the decrease of alanine aminotransferase (ALT) in L-02 hepatocytes caused by acute drug-induced liver injury; C showed that ZML1 can restore the decrease of total superoxide dismutase (T-SOD) in L-02 hepatocytes caused by acute drug-induced liver injury.

[0029] Figure 2The therapeutic effects of ZML1 and ursodeoxycholic acid on acute drug-induced liver injury are shown, wherein A shows that both ZML1 and ursodeoxycholic acid can treat acute drug-induced liver injury caused by alcohol, restore the increase in the proportion of liver in body weight, and reduce liver swelling; B shows that ZML1 and ursodeoxycholic acid can reduce the increase in serum AST; C shows that both ZML1 and ursodeoxycholic acid can reduce the increase in serum ALT.

[0030] Figure 3 The therapeutic effects of ZML1 and ursodeoxycholic acid on acute drug-induced liver injury are shown; A and B show that alcohol causes vacuoles in liver cells, neutrophil aggregation and partial necrosis; C and D show that ZML1 and ursodeoxycholic acid can improve tissue swelling and inflammation, and the therapeutic effect of ZML1 is significantly better than that of ursodeoxycholic acid; E and F show liver lipid metabolism disorders caused by alcohol; G and H show that ZML1 can improve liver lipid deposition and promote the excretion of liver fat droplets, while ursodeoxycholic acid has no obvious therapeutic effect. DETAILED DESCRIPTION

[0031] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0032] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that the upper and lower limits of the scope and each intermediate value therebetween are specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0033] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art to which the invention belongs. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0034] application

[0035] In one aspect of the present invention, there is provided a use of compound ZML1 in the preparation of a drug for preventing or treating acute drug-induced liver injury, wherein the compound ZML1 has a structure shown in formula I:

[0036]

[0037] In the present invention, compound ZML1 is α-terpineol, CAS No.: 10482-56-1, molecular weight: 154.249, molecular formula: C 10 H 18 O.

[0038] In the present invention, the acute drug-induced liver injury includes liver injury caused by prescription or over-the-counter chemical drugs, biological preparations, natural medicines, health products and / or excipients. The determination of the acute drug-induced liver injury can be carried out by methods known in the art, such as detecting the amount of alanine aminotransferase, aspartate aminotransferase, etc. in serum.

[0039] In the present invention, the prevention or treatment includes at least one of the following:

[0040] (1) Reduce or restore the amount of serum alanine aminotransferase;

[0041] (2) reduce or restore the amount of serum aspartate aminotransferase;

[0042] (3) Increase or restore the amount of total superoxide dismutase in liver tissue;

[0043] (4) Reduce swelling and inflammation of liver tissue;

[0044] (5) Reduce liver parenchymal lesions;

[0045] (6) Reduce lipid deposition;

[0046] (7) Promote liver damage repair;

[0047] (8) restore or protect liver cell morphology or function;

[0048] (9) Restore or protect liver function.

[0049] In the present invention, the term "prevention or treatment" refers to therapeutic treatment and preventive or prophylactic measures, the purpose of which is to prevent or slow down (reduce) undesirable physiological changes or disorders, such as increases in liver damage indicators. Beneficial or desired clinical results include, but are not limited to, the following results, whether detectable or undetectable, including relief of symptoms, reduction in disease severity, stabilization of the disease state (i.e., no worsening), delay or slowing of disease progression, improvement or alleviation of the disease state, and relief (whether partial or complete). Those in need of treatment include those who already have acute drug-induced liver injury or liver injury-related diseases or those who need to prevent or improve acute drug-induced liver injury or liver injury-related diseases.

[0050] In the present invention, the prevention or treatment is achieved by administering a therapeutically effective amount of the compound ZML1 to the subject. The term "effective amount" as used herein means the amount of a drug or medicament that causes a biological or pharmaceutical response of a tissue, system, animal or human being, such as that pursued by a researcher or clinician. In addition, the term "therapeutically effective amount" means that, compared with a corresponding subject that has not received the amount, the amount of improved treatment, cure, prevention or alleviation of a disease, disorder or side effect, or the amount that reduces the rate of progression of a disease or condition. The term also includes within its scope the amount that effectively enhances normal physiological function. Generally, the effective amount herein varies according to various factors, such as a given drug or compound, a pharmaceutical preparation, a route of administration, the type of disease or disorder, the subject being treated, etc., but can still be routinely determined by a person skilled in the art. The effective amount of the compound ZML1 of the present invention can be easily determined by a person skilled in the art by conventional methods known in the art.

[0051] In the present invention, the daily dosage of compound ZML1 is usually 1-1000 mg / kg, preferably 1-900 mg / kg, also preferably 1-800 mg / kg, further preferably 1-700 mg / kg, more preferably 1-600 mg / kg, more preferably 1-500 mg / kg, more preferably 1-400 mg / kg, more preferably 1-300 mg / kg, more preferably 1-200 mg / kg, more preferably 1-100 mg / kg, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 mg / kg. It can be administered once a day in a single dose, can be administered multiple times a day, or can be used at intervals.

[0052] In the present invention, the subject includes mammals, including mice, rabbits, cats, dogs, cows, sheep, pigs, humans, etc.

[0053] There is no particular limitation on the administration method of the drug of the present invention, and representative administration methods include, but are not limited to, intravenous injection, intraperitoneal injection, intramuscular injection, intravenous drip, oral administration, enema, spray, etc. Accordingly, the drug of the present invention can be prepared into various clinically acceptable dosage forms, including oral dosage forms, injection dosage forms, local administration dosage forms or external dosage forms, etc.

[0054] Pharmaceutical composition

[0055] One aspect of the present invention provides a pharmaceutical composition for preventing or treating acute drug-induced liver injury, comprising compound ZML1 and a pharmaceutically acceptable carrier.

[0056] In the present invention, the pharmaceutically acceptable carrier includes at least one of a diluent, a filler, an absorbent, a wetting agent, a binder, a disintegrant, a lubricant, a sweetener, a preservative and an antioxidant. Some non-limiting examples of materials that can be used as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, methylcellulose, ethylcellulose, microcrystalline cellulose and cellulose acetate; (4) tragacanth powder; (5) malt; (6) gelatin; (7) lubricants, such as magnesium stearate, sodium lauryl sulfate and talc; (8) cocoa butter and suppository wax; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as Glycerol, sorbitol, mannitol and polyethylene glycol (PEG); (12) esters such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) pH buffered solutions; (21) polyesters, polycarbonates and / or polyanhydrides; (22) fillers such as polypeptides and amino acids; (23) serum components such as serum albumin, HDL and LDL; (24) C2-C12 alcohols such as ethanol; and (25) other non-toxic compatible substances used in pharmaceutical formulations. Terms such as "excipient", "carrier", "pharmaceutically acceptable carrier" and the like are used interchangeably herein.

[0057] In the present invention, a pharmaceutically acceptable carrier is involved in carrying or delivering a drug from one organ or part of the body to another organ or part of the body. Each carrier is "acceptable" if it is compatible with the other ingredients of the formulation (eg, compound ZML1) and does not harm the patient.

[0058] In the present invention, the dosage of the pharmaceutical composition depends on many factors, such as the nature and severity of the disease to be prevented or treated, the sex, age, weight, personality and individual response of the patient or animal, the route of administration, the number of administrations, and the purpose of treatment, so the therapeutic dose of the pharmaceutical composition of the present invention can vary widely. The suitable dosage range of the pharmaceutical composition of the present invention is preferably 0.01-1000 mg / kg body weight per day, more preferably 0.01-200 mg / kg body weight. The above dosage can be administered in a single dosage form or divided into several, such as two, three or four dosage forms. And the dosage applied is within the predictable range of the clinician or laboratory personnel, for example, by effectiveness and safety testing, the dosage can be appropriately adjusted to obtain the optimal dosage.

[0059] Joint Application

[0060] One aspect of the present invention provides the use of the compound ZML1 in the preparation of a drug for treating acute drug-induced liver injury in combination with other drugs.

[0061] In the present invention, the other drugs include any drugs that can be used to treat acute drug-induced liver injury, examples of which include but are not limited to ursodeoxycholic acid, N-acetylcysteine, magnesium isoglycyrrhizinate, glucocorticoids, adenosine methionine, silymarin, bicyclol, glycyrrhizic acid preparations, bile acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, tauroursodeoxycholic acid, hyodeoxycholic acid, taurocholic acid, glycocholic acid, arbidol hydrochloride, etc.

[0062] Example 1

[0063] The following shows the therapeutic effect of ZML1 on acute drug-induced liver injury at the cellular level.

[0064] 1. Experimental Methods

[0065] 1.1 Cell culture and treatment

[0066] Normal human hepatocytes (L02 cells) were cultured in a 37°C, 5% CO2 incubator using DMEM supplemented with 10% fetal bovine serum (FBS). When the cells reached 90% confluence, they were randomly divided into a control (WT) group, an ethanol injury (EtOH) group, and an ethanol injury plus ZML1 treatment (ZML1) group, wherein the control group was treated with phosphate buffered saline (PBS); the EtOH group was added with 1000mM EtOH solution and cultured for 24h; the ZML1 group was added with 1000mM EtOH solution, incubated for 6h, and then 100nM ZML1 was added and cultured for 24h.

[0067] 1.2 Detection of cellular AST, ALT, and SOD activity

[0068] Each group of cells was washed with ice PBS and suspended, and homogenized at 4000 rpm / min in an ice bath until the cells were fully broken. The cell lysate was tested according to the instructions of the alanine aminotransferase, aspartate aminotransferase, and total superoxide dismutase kits, and each sample was repeated 3 times.

[0069] 2. Experimental results

[0070] The results showed that ZML1 could increase or restore the levels of AST, ALT and SOD in hepatocytes caused by acute drug-induced liver injury.

[0071] Example 2

[0072] The following shows the therapeutic effect of ZML1 on acute drug-induced liver injury at the animal level.

[0073] 1. Experimental Methods

[0074] 1.1 Animal grouping and treatment

[0075] Eight-week-old C57BL / 6J male mice were adapted for 3 days at a temperature of 20-25°C, relative humidity of 50%-55%, 12h light / 12h dark alternation, free food and water. Then they were randomly divided into a control (WT) group, an ethanol injury (EtOH) group, an ethanol injury and ZML1 treatment (ZML1) group, and an ethanol injury and ursodeoxycholic treatment (Ursodeoxycholic) group, with 3 mice in each group. All animal experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The animal study was reviewed and approved by the Laboratory Animal Welfare and Ethics Committee of Peking University.

[0076] After the adaptation period, mice in the EtOH, ZML1, and ursodeoxycholic acid groups were gavaged with ethanol solution at a dose of 6 g / kg body weight for two consecutive times with an interval of 12 hours, and the WT group was gavaged with an equal volume of normal saline. 6 hours after the last gavage, mice in the ZML1 and ursodeoxycholic acid groups were intraperitoneally injected with the corresponding drug solution (the drug solution consisted of drug and corn oil) for treatment at a dose of 100 mg / kg body weight, and the WT and EtOH groups were intraperitoneally injected with an equal volume of corn oil. All mice were in a suitable living environment and had free access to food and water.

[0077] 1.2 Body mass determination

[0078] The mice's condition was continuously observed from the beginning of the adaptation period to the end of treatment, and their body weight was weighed and recorded 6 hours after the end of treatment.

[0079] 1.3 Serum biochemical analysis

[0080] After 6 hours of treatment, the mice were anesthetized and blood samples were obtained through the retro-orbital sinus (mouse eye socket). The collected blood was allowed to stand overnight at 4°C and then centrifuged at 3500 rpm / min to separate serum and stored at -80°C for further analysis.

[0081] AST and ALT in serum were detected using corresponding detection kits according to the manufacturer's instructions.

[0082] 1.4 Determination of liver tissue organ index

[0083] After the eyeball blood was collected, the mice were killed by cervical dislocation, dissected, and the liver was removed and weighed. The organ index was calculated according to the following formula: organ index = liver weight (g) / mouse body weight (g).

[0084] 1.5 Liver histological analysis

[0085] The liver tissues from the same position of each mouse were embedded in paraffin and OCT, and stained with hematoxylin & eosin (H&E) and oil red O, respectively. The details are as follows:

[0086] For H&E staining, fresh liver tissues were fixed with 4% paraformaldehyde, embedded in paraffin after dehydration, and cut into 5 μm sections. The sections underwent a series of treatments, including ethanol fixation, hematoxylin staining, hydrochloric acid ethanol decolorization, eosin staining, alcohol gradient treatment, and xylene treatment, and then observed under an optical microscope after sealing with neutral glue.

[0087] For Oil Red O staining, fresh liver tissue was fixed with 4% paraformaldehyde and frozen in OCT, and cut into 10 μm sections using a cryostat. After rinsing with distilled water and 60% isopropanol, the sections were treated with 60% Oil Red O staining solution, rinsed again with distilled water, restained with hematoxylin, and then lipid accumulation in hepatocytes was observed under a light microscope. Oil Red O staining was analyzed using software.

[0088] 1.6 Data Statistics and Processing

[0089] This example uses software to perform statistics and analysis of experimental data, and the results are expressed in the form of mean ± standard error (Mean ± SEM). A single-factor ANOVA analysis of variance was used for significant analysis between multiple groups of data, and significance was expressed as *p<0.05, **p<0.01, ***p<0.001.

[0090] 2. Experimental results

[0091] The results showed that both ZML1 and ursodeoxycholic acid can treat acute drug-induced liver injury caused by alcohol, restore the increase in the proportion of liver in body weight, reduce liver swelling and reduce serum AST and ALT levels. In addition, both ZML1 and ursodeoxycholic acid can treat liver parenchymal lesions of acute liver injury caused by alcohol, improve tissue swelling and inflammation, and alleviate liver lipid metabolism disorders caused by alcohol, and the efficacy of ZML1 is significantly better than that of ursodeoxycholic acid.

[0092] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some of the technical features therein by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. Use of compound ZML1 in the preparation of a drug for preventing or treating acute drug-induced liver injury, characterized in that: The compound ZML1 has a structure shown in Formula I:

2. The use of the compound ZML1 according to claim 1 in the preparation of a drug for preventing or treating acute drug-induced liver injury, characterized in that: The acute drug-induced liver injury includes liver injury caused by prescription or over-the-counter chemical drugs, biological preparations, natural medicines, health products and / or excipients.

3. Use of the compound ZML1 according to claim 1 in the preparation of a drug for preventing or treating acute drug-induced liver injury, characterized in that: The prevention or treatment comprises at least one of the following: (1) Reduce or restore the amount of serum alanine aminotransferase; (2) reduce or restore the amount of serum aspartate aminotransferase; (3) Increase or restore the amount of total superoxide dismutase in liver tissue; (4) Reduce swelling and inflammation of liver tissue; (5) Reduce liver parenchymal lesions; (6) Reduce lipid deposition; (7) Promote liver damage repair; (8) restore or protect liver cell morphology or function; (9) Restore or protect liver function.

4. Use of the compound ZML1 according to claim 1 in the preparation of a drug for preventing or treating acute drug-induced liver injury, characterized in that: The prevention or treatment is achieved by administering a therapeutically effective amount of the compound ZML1 to the subject.

5. Use of the compound ZML1 according to claim 4 in the preparation of a drug for preventing or treating acute drug-induced liver injury, characterized in that: The effective amount is 1-1000 mg / kg.

6. Use of the compound ZML1 according to claim 4 in the preparation of a drug for preventing or treating acute drug-induced liver injury, characterized in that: The subject includes a mammal.

7. A pharmaceutical composition for preventing or treating acute drug-induced liver injury, characterized in that: The pharmaceutical composition comprises compound ZML1 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, characterized in that The pharmaceutically acceptable carrier includes at least one of a diluent, a filler, an absorbent, a wetting agent, a binder, a disintegrant, a lubricant, a sweetener, a preservative and an antioxidant.

9. Use of compound ZML1 in the preparation of drugs for treating acute drug-induced liver injury in combination with other drugs.

10. Use of the compound ZML1 according to claim 9 in the preparation of a drug for treating acute drug-induced liver injury in combination with other drugs, characterized in that: The other drugs include at least one of ursodeoxycholic acid, N-acetylcysteine, magnesium isoglycyrrhizinate, glucocorticoids, adenosylmethionine, silymarin, bicyclol, glycyrrhizic acid preparations, cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, tauroursodeoxycholic acid, hyodeoxycholic acid, taurocholic acid, glycocholic acid and arbidol hydrochloride.

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