Use of compound zml1 in the preparation of a medicament for the treatment of acute drug-induced liver injury

Abstract

The application discloses application of a compound ZML1 in preparation of a medicine for treating acute drug-induced liver injury. Through in-vivo and in-vitro experiments, it is found that ZML1 can reverse acute liver injury only by acting for several hours, for example, restoring normal morphology of hepatocytes, reducing lipid deposition, rapidly improving damage performance of various transaminases and the like. The treatment effect of the compound ZML1 of the application on various liver injury indexes is superior to that of existing liver-protecting medicines, especially in improving lipid deposition of hepatocytes, and the compound ZML1 shows more excellent curative effect. Therefore, ZML1 has excellent drug property in treating acute drug-induced liver injury and protecting liver, and thus has a wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of natural medicine technology, and in particular relates to the application of compound ZML1 in the preparation of a drug for treating acute drug-induced liver injury. Background Technology

[0002] Diagnostic criteria for 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 gamma-glutamyl transferase or after excluding primary skeletal pathological changes); ALT ≥ 3 × ULN and total bilirubin (TB) > 2 × ULN. In addition, improvement in liver function indicators after drug discontinuation; rapid induction of liver injury upon occasional re-administration; and liver function tests are important clues for diagnosing DILI.

[0003] The basic principles of DILI treatment include timely discontinuation of suspected hepatotoxic drugs and avoiding re-use of suspected or similar drugs as much as possible; a thorough weighing of the risks of disease progression due to drug discontinuation versus the risk of further liver damage due to continued use; selection of appropriate drug therapy based on the clinical type of DILI; and emergency liver transplantation may be considered for critically ill patients such as those with acute / subacute liver failure.

[0004] Currently, for severe cases, early acute liver failure, and intrinsic liver injury (DILI) caused by acetaminophen, N-acetylcysteine ​​can be used for treatment; for acute hepatocellular injury-type or mixed DILI, magnesium isoglycyrrhizinate can be used; for patients with significant hypersensitivity or autoimmune signs, and whose biochemical indicators do not improve significantly or continue to worsen after discontinuation of hepatotoxic drugs, glucocorticoids can be used; for cholestatic DILI, ursodeoxycholic acid and S-adenosylmethionine can be used; for mild to moderate hepatocellular injury-type and mixed DILI, silymarin can be used for milder inflammation, while bicyclol and glycyrrhizic acid preparations can be used for more severe inflammation. However, current treatments with these drugs are mainly symptomatic, have a slow onset of action, are not very effective in treating lipid deposition in the liver, and are difficult to reverse liver tissue and cell damage. Therefore, there is an urgent need to develop a drug that can effectively improve lipid deposition in the liver and reverse liver tissue and cell damage. Summary of the Invention

[0005] To address at least some of the technical problems in the prior art, the present invention provides the use of compound ZML1 in the preparation of a medicament for treating acute drug-induced liver injury. Specifically, the present invention includes the following.

[0006] A first aspect of the present invention provides the use of compound ZML1 in the preparation of a medicament for the prevention or treatment of acute drug-induced liver injury, wherein said compound ZML1 has the structure shown in Formula I:

[0007]

[0008] In some embodiments, the use of compound ZML1 according to the present invention in the preparation of a medicament for the prevention or treatment of 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 agents, natural medicines, health products and / or excipients.

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

[0010] (1) Reduce or restore serum alanine aminotransferase levels;

[0011] (2) Reduce or restore serum aspartate aminotransferase levels;

[0012] (3) Increase or restore the total amount of superoxide dismutase in liver tissue;

[0013] (4) Reduces liver tissue swelling and inflammation;

[0014] (5) Reduce liver parenchymal lesions;

[0015] (6) Reduces lipid deposition;

[0016] (7) Promotes liver damage repair;

[0017] (8) To restore or protect the morphology or function of hepatocytes;

[0018] (9) Restore or protect liver function.

[0019] In some embodiments, the use of compound ZML1 according to the present invention in the preparation of a medicament for the prevention or treatment of acute drug-induced liver injury is described, wherein the prevention or treatment is achieved by administering a therapeutically effective amount of compound ZML1 to a subject.

[0020] In some embodiments, the use of compound ZML1 according to the present invention in the preparation of a medicament for the prevention or treatment of acute drug-induced liver injury, wherein the effective amount is 1-1000 mg / kg.

[0021] In some embodiments, the use of compound ZML1 according to the present invention in the preparation of a medicament for the prevention or treatment of acute drug-induced liver injury, wherein the subject includes mammals.

[0022] In a second aspect, the present invention provides a pharmaceutical composition for the prevention or treatment of acute drug-induced liver injury, comprising compound ZML1 and a pharmaceutically acceptable carrier.

[0023] In some embodiments, the pharmaceutical composition according to the present invention includes, wherein the pharmaceutically acceptable carrier comprises at least one of a diluent, filler, absorbent, wetting agent, binder, disintegrant, lubricant, sweetener, preservative, and antioxidant.

[0024] A third aspect of the invention provides the use of compound ZML1 in the preparation of a medicament for the treatment of acute drug-induced liver injury in combination with other drugs.

[0025] In some embodiments, the use of compound ZML1 according to the present invention in the preparation of a medicament 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, S-adenosylmethionine, silymarin, bicyclol, glycyrrhizic acid preparations, cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, tauroursodeoxycholic acid, porcine deoxycholic acid, taurocholic acid, glycocholic acid, and arbidol hydrochloride.

[0026] This invention, through in vivo and in vitro experiments, demonstrates that ZML1 can reverse acute liver injury within just a few hours, such as restoring normal hepatocyte morphology, reducing lipid deposition, and rapidly improving the damaged manifestations of various transaminases. In a mouse model of acute liver injury, the use of ZML1 resulted in liver indicators returning to near-normal levels compared to the injured group. Both in vitro and in vivo experimental results of ZML1 were compared with those of ursodeoxycholic acid, the current "gold standard" hepatoprotective drug. ZML1 showed superior therapeutic effects on various injury indicators compared to ursodeoxycholic acid, particularly demonstrating superior efficacy in improving hepatocyte lipid deposition. Therefore, ZML1 possesses excellent drug-like properties for treating acute drug-induced liver injury and protecting the liver, thus showing broad application prospects. Attached Figure Description

[0027] Figure 1 The results show that ZML1 can restore functional impairment caused by acute drug-induced liver injury in vitro. Specifically, A shows that ZML1 can restore the decrease in aspartate aminotransferase (AST) in L-02 hepatocytes caused by acute drug-induced liver injury; B shows that ZML1 can restore the decrease in alanine aminotransferase (ALT) in L-02 hepatocytes caused by acute drug-induced liver injury; and C shows that ZML1 can restore the decrease in total superoxide dismutase (T-SOD) in L-02 hepatocytes caused by acute drug-induced liver injury.

[0028] Figure 2The therapeutic effects of ZML1 and ursodeoxycholic acid on acute drug-induced liver injury were shown. In A, it was shown that both ZML1 and ursodeoxycholic acid could treat acute drug-induced liver injury caused by alcohol, restore the increased liver weight ratio, and reduce liver swelling. In B, it was shown that both ZML1 and ursodeoxycholic acid could reduce the elevation of serum AST. In C, it was shown that both ZML1 and ursodeoxycholic acid could reduce the elevation of serum ALT.

[0029] Figure 3 The therapeutic effects of ZML1 and ursodeoxycholic acid on acute drug-induced liver injury are shown. A and B illustrate alcohol-induced hepatocyte vacuolation, neutrophil aggregation, and partial necrosis. C and D show that both ZML1 and ursodeoxycholic acid can improve tissue swelling and inflammation, with ZML1 showing significantly better efficacy than ursodeoxycholic acid. E and F illustrate alcohol-induced hepatic lipid metabolism disorders. G and H show that ZML1 can improve hepatic lipid deposition and promote lipid droplet excretion, while ursodeoxycholic acid has no significant effect. Detailed Implementation

[0030] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0031] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that the upper and lower limits of the range and each intermediate value between them are specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0032] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0033] application

[0034] In one aspect, the present invention provides the use of compound ZML1 in the preparation of a medicament for the prevention or treatment of acute drug-induced liver injury, wherein compound ZML1 has the structure shown in Formula I:

[0035]

[0036] In this invention, compound ZML1 is α-terpineol, CAS number: 10482-56-1, molecular weight: 154.249, molecular formula: C 10 H 18 O.

[0037] In this invention, acute drug-induced liver injury includes liver injury caused by prescription or over-the-counter chemical drugs, biological agents, natural medicines, health products, and / or excipients. The determination of acute drug-induced liver injury can be performed using methods known in the art, such as detecting the levels of alanine aminotransferase, aspartate aminotransferase, etc., in serum.

[0038] In this invention, the prevention or treatment includes at least one of the following:

[0039] (1) Reduce or restore serum alanine aminotransferase levels;

[0040] (2) Reduce or restore serum aspartate aminotransferase levels;

[0041] (3) Increase or restore the total amount of superoxide dismutase in liver tissue;

[0042] (4) Reduces liver tissue swelling and inflammation;

[0043] (5) Reduce liver parenchymal lesions;

[0044] (6) Reduces lipid deposition;

[0045] (7) Promotes liver damage repair;

[0046] (8) To restore or protect the morphology or function of hepatocytes;

[0047] (9) Restore or protect liver function.

[0048] In this invention, the term "prevention or treatment" refers to therapeutic treatments and preventive or therapeutic measures aimed at preventing or mitigating (reducing) undesirable physiological changes or disturbances, such as elevated levels of liver injury markers. Beneficial or desired clinical outcomes include, but are not limited to, the following, whether detectable or undetectable: symptom relief, reduction in disease severity, stabilization of the disease state (i.e., no worsening), delay or slowing of disease progression, improvement or mitigation of the disease state, and reduction (whether partial or complete). Those requiring treatment include individuals who already have acute drug-induced liver injury or liver injury-related conditions, or those who require prevention or improvement of acute drug-induced liver injury or liver injury-related conditions.

[0049] In this invention, the prevention or treatment is achieved by administering a therapeutically effective amount of the compound ZML1 to a subject. As used herein, the term "effective amount" refers to the amount of a drug or agent that elicits a biological or pharmaceutical response in a tissue, system, animal, or human, as sought by, for example, an investigator or clinician. Furthermore, the term "therapeuticly effective amount" refers to the amount that causes improved treatment, cure, prevention, or reduction of disease, symptom, or side effects, or reduces the rate of progression of the disease or condition, compared to a corresponding subject who did not receive that amount. The term also includes, within its scope, amounts that effectively enhance normal physiological function. Generally, the effective amount as used herein varies depending on various factors, such as the given drug or compound, pharmaceutical formulation, route of administration, type of disease or symptom, subject being treated, etc., but can still be conventionally determined by those skilled in the art. The effective amount of the compound ZML1 of this invention can be readily determined by those skilled in the art using conventional methods known in the art.

[0050] In this invention, the daily dosage of compound ZML1 is typically 1-1000 mg / kg, preferably 1-900 mg / kg, even more 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, and even 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, and 100 mg / kg. It can be administered as a single daily dose, divided into multiple daily doses, or used at intervals.

[0051] In this invention, the subjects include mammals, including mice, rabbits, cats, dogs, cattle, sheep, pigs, humans, etc.

[0052] There are no particular limitations on the administration method of the drug of this invention. Representative administration methods include, but are not limited to, intravenous injection, intraperitoneal injection, intramuscular injection, intravenous drip, oral administration, enema, and spray. Accordingly, the drug of this invention can be formulated into various clinically acceptable dosage forms, including oral dosage forms, injectable dosage forms, topical dosage forms, or external dosage forms.

[0053] Pharmaceutical Composition

[0054] In one aspect, the present invention provides a pharmaceutical composition for the prevention or treatment of acute drug-induced liver injury, comprising compound ZML1 and a pharmaceutically acceptable carrier.

[0055] In this invention, the pharmaceutically acceptable carrier includes at least one of diluents, fillers, absorbents, wetting agents, binders, disintegrants, lubricants, sweeteners, preservatives, and antioxidants. Some non-limiting examples of materials that can serve 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 carboxymethyl cellulose, methyl cellulose, ethyl cellulose, microcrystalline cellulose, and cellulose acetate; (4) tragacanth gum powder; (5) malt; (6) gelatin; (7) lubricants, such as magnesium stearate, sodium lauryl sulfate, and talc; (8) cocoa butter and sulphurine; (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... (12) Glycerin, sorbitol, mannitol, and polyethylene glycol (PEG); (13) Esters, such as ethyl oleate and ethyl laurate; (14) Agar; (15) Buffers, such as magnesium hydroxide and aluminum hydroxide; (16) Alginate; (17) Atherless water; (18) Isotonic saline; (19) Ringer's solution; (20) Ethanol; (21) pH buffer solution; (22) Polyesters, polycarbonates, and / or polyanhydrides; (23) Fillers, such as peptides and amino acids; (24) Serum components, such as serum albumin, HDL, and LDL; (25) C2-C12 alcohols, such as ethanol; and (26) Other non-toxic and compatible substances used in pharmaceutical formulations. Terms such as “excipient,” “carrier,” and “pharmaceutically acceptable carrier” are used interchangeably herein.

[0056] In this invention, pharmaceutically acceptable carriers are used to transport or deliver drugs from one organ or part of the body to another organ or part of the body. Each carrier is "acceptable" meaning that it is compatible with other components of the formulation (e.g., compound ZML1) and does not harm the patient.

[0057] In this 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, frequency of administration, and therapeutic purpose. Therefore, the therapeutic dosage of the pharmaceutical composition of this invention can vary widely. The suitable daily dosage range of the pharmaceutical composition of this invention is preferably 0.01-1000 mg / kg body weight, more preferably 0.01-200 mg / kg body weight. The above dosage can be administered in a single dose or divided into several doses, such as two, three, or four doses. The administered dosage is within the predictable range of clinicians or laboratory personnel, and can be appropriately adjusted through efficacy and safety testing to obtain the optimal dosage.

[0058] Combined applications

[0059] In one aspect, the present invention provides the use of compound ZML1 in the preparation of a medicament for the treatment of acute drug-induced liver injury in combination with other drugs.

[0060] In this 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, S-adenosylmethionine, silymarin, bicyclol, glycyrrhizic acid preparations, cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, tauroursodeoxycholic acid, porcine deoxycholic acid, taurocholic acid, glycocholic acid, arbidol hydrochloride, etc.

[0061] Example 1

[0062] The following demonstrates the therapeutic effect of ZML1 on acute drug-induced liver injury at the cellular level.

[0063] 1. Experimental Methods

[0064] 1.1 Cell Culture and Treatment

[0065] Human normal hepatocytes (L02 cells) were cultured in DMEM supplemented with 10% fetal bovine serum (FBS) at 37°C in a 5% CO2 incubator. When the cells reached 90% confluence, they were randomly divided into a control (WT) group, an ethanol-damaged (EtOH) group, and an ethanol-damaged group treated with ZML1 (ZML1) group. The control group was treated with phosphate-buffered saline (PBS); the EtOH group was incubated with 1000 mM EtOH solution for 24 h; and the ZML1 group was incubated with 1000 mM EtOH solution for 6 h, followed by incubation with 100 nM ZML1 for another 24 h.

[0066] 1.2 Detection of AST, ALT, and SOD activities in cells

[0067] Each group of cells was washed with ice-cold PBS and resuspended. Cells were homogenized at 4000 rpm / min on ice until fully lysed. Cell lysis buffer was analyzed according to the kit instructions for alanine aminotransferase, aspartate aminotransferase, and total superoxide dismutase, with each sample tested in triplicate.

[0068] 2. Experimental Results

[0069] 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.

[0070] Example 2

[0071] The following demonstrates the therapeutic effect of ZML1 on acute drug-induced liver injury in animals.

[0072] 1. Experimental Methods

[0073] 1.1 Animal grouping and treatment

[0074] Eight-week-old male C57BL / 6J mice were acclimatized for three days under conditions of 20-25°C, 50%-55% relative humidity, 12-hour light / 12-hour dark alternation, and free access to food and water. They were then randomly assigned to four groups: a control (WT) group, an ethanol-induced toxicity (EtOH) group, an ethanol-induced toxicity group treated with ZML1 (ZML1), and an ethanol-induced toxicity group treated with ursodeoxycholic acid (ursodeoxycholic acid), with three mice in each group. All animal experiments were conducted in accordance with the National Institutes of Health's Guidelines for the Care and Use of Laboratory Animals. This animal study was reviewed and approved by the Laboratory Animal Welfare and Ethics Committee of Peking University.

[0075] After the adaptation period, mice in the EtOH, ZML1, and ursodeoxycholic acid groups were administered ethanol solution by gavage at a dose of 6 g / kg body weight twice, with an interval of 12 hours. The WT group was administered an equal volume of physiological saline by gavage. Six hours after the last gavage, mice in the ZML1 and ursodeoxycholic acid groups were treated with intraperitoneal injection of the corresponding drug solution (composed of the drug and corn oil) at a dose of 100 mg / kg body weight. The WT and EtOH groups were treated with intraperitoneal injection of an equal volume of corn oil. All mice were kept in a suitable living environment with free access to food and water.

[0076] 1.2 Body weight determination

[0077] From the start of the mouse adaptation period to the end of treatment, the mice's condition was continuously observed. Six hours after the end of treatment, the mice's body weight was weighed and recorded.

[0078] 1.3 Serum Biochemical Analysis

[0079] Six hours after treatment, mice were anesthetized, and blood samples were obtained through the posterior orbital sinus (mouse eye socket). The collected blood was allowed to stand overnight at 4°C, then centrifuged at 3500 rpm / min to separate the serum, which was stored at -80°C for further analysis.

[0080] Serum AST and ALT were detected using corresponding detection kits and according to the manufacturer's instructions.

[0081] 1.4 Determination of Liver Organ Index

[0082] After blood was collected from the eyeballs, the mice were euthanized by cervical dislocation, dissected, and the livers were removed and weighed. The organ index was calculated using the following formula: Organ Index = Liver weight (g) / Mouse body weight (g).

[0083] 1.5 Liver Histological Analysis

[0084] Liver tissue from the same location in each mouse was embedded in paraffin and OCT, and stained with hematoxylin and eosin (H&E) and Oil Red O, respectively. Details are as follows:

[0085] For H&E staining, fresh liver tissue was fixed with 4% paraformaldehyde, dehydrated, embedded in paraffin, and cut into 5 μm sections. The sections underwent a series of treatments, including ethanol fixation, hematoxylin staining, hydrochloric acid-ethanol destaining, eosin staining, alcohol gradient treatment, and xylene treatment, and were then sealed with neutral glue and observed under an optical microscope.

[0086] For Oil Red O staining, fresh liver tissue was fixed with 4% paraformaldehyde and frozen in OCT. Sections were then 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 the lipid accumulation in hepatocytes was observed under a light microscope. Oil Red O staining was analyzed using software.

[0087] 1.6 Data Statistics and Processing

[0088] This embodiment uses software to perform statistical analysis of experimental data, and the results are expressed as mean ± standard error (Mean ± SEM). Significance analysis among multiple groups of data was performed using ANOVA one-way ANOVA, with significance expressed as *p<0.05, **p<0.01, and ***p<0.001.

[0089] 2. Experimental Results

[0090] The results showed that both ZML1 and ursodeoxycholic acid could treat alcohol-induced acute drug-induced liver injury, restore the increased liver weight-to-body weight ratio, reduce liver swelling, and lower serum AST and ALT levels. Furthermore, both ZML1 and ursodeoxycholic acid could treat parenchymal liver lesions caused by alcohol-induced acute liver injury, improve tissue swelling and inflammation, and alleviate alcohol-induced hepatic lipid metabolism disorders. Moreover, the efficacy of ZML1 was significantly superior to that of ursodeoxycholic acid.

[0091] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. These modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. The use of compound ZML1 in the preparation of drugs for the prevention or treatment of alcoholic liver injury, characterized in that, The compound ZML1 has the structure shown in Formula I: Equation I.

2. The use of compound ZML1 according to claim 1 in the preparation of a medicament for the prevention or treatment of alcoholic liver injury, characterized in that, The prevention or treatment includes at least one of the following: (1) Reduce or restore serum alanine aminotransferase levels; (2) Reduce or restore serum aspartate aminotransferase levels; (3) Increase or restore the total amount of superoxide dismutase in liver tissue; (4) Reduces liver tissue swelling and inflammation; (5) Reduce liver parenchymal lesions; (6) Reduce lipid deposition; (7) Promotes liver damage repair; (8) To restore or protect the morphology or function of hepatocytes; (9) Restore or protect liver function.

3. The use of compound ZML1 according to claim 1 in the preparation of a medicament for the prevention or treatment of alcoholic liver injury, characterized in that, The prevention or treatment is achieved by administering a therapeutically effective amount of the compound ZML1 to the subject.

4. The use of compound ZML1 according to claim 3 in the preparation of a medicament for the prevention or treatment of alcoholic liver injury, characterized in that, The effective amount is 1-1000 mg / kg.

5. The use of compound ZML1 according to claim 3 in the preparation of a medicament for the prevention or treatment of alcoholic liver injury, characterized in that, The subjects included mammals.

6. The use of compound ZML1 according to claim 1 in the preparation of a medicament for the prevention or treatment of alcoholic liver injury, characterized in that, The drug further includes a pharmaceutically acceptable carrier.

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