Application of combination of ligustrazine and inosine in preparation of medicine for dispelling effects of alcohol and protecting liver

Abstract

The invention discloses application of combination of ligustrazine and inosine in preparation of a medicine for dispelling effects of alcohol and protecting liver, and belongs to the technical field of medicine research and development. The ligustrazine and inosine are combined for intervention, so that behavioral characteristic data and serum metabolism indexes of mice suffering from acute alcoholism after drinking can be improved, the oxidative stress level in the bodies of the mice suffering from alcoholic liver injury can be reduced, the conditions of inflammatory response, fat accumulation and the like can be relieved, and dose correlation is achieved. The combined use of ligustrazine and inosine can enhance the phosphorylation level of PI3K and AKT proteins by activating an ESR1 / PI3K / AKT signal channel and an Nrf2 / HO-1 signal channel, reverse the low expression of inflammatory factors IL-10 and the high expression of TNF-alpha and IL-6, and relieve the damage of alcohol to the liver of a mouse. Based on the discovery, the combination of ligustrazine and inosine has the effects of dispelling the effects of alcohol and protecting the liver, and a new choice is provided for research, development and preparation of the medicines for dispelling the effects of alcohol and protecting the liver.

Description

Technical Field

[0001] This invention belongs to the field of drug development technology, specifically involving the application of ligustrazine combined with inosine in the preparation of hangover relief and liver protection drugs. Background Technology

[0002] Ligusticum chuanxiong, a plant belonging to the genus Artemisia in the family Apiaceae, is a common traditional Chinese medicine. Due to its excellent antioxidant capacity, it has been used for centuries to treat cardiovascular and cerebrovascular diseases. Isolation of Ligusticum chuanxiong yields numerous components, including alkaloid monomers, volatile oils, polysaccharides, lactones, and organic acids. Among these, ligustrazine, an alkaloid, has been widely used.

[0003] Inosine, also known as hypoxanthine inosine, is a common nutrient found in meat products such as livestock and poultry, as well as food additives such as chicken essence and monosodium glutamate. It is a nucleoside compound formed by the combination of hypoxanthine and ribose. Inosine is commonly used clinically as a hepatoprotective drug, assisting in the treatment of acute and chronic hepatitis, cirrhosis, and hepatic encephalopathy.

[0004] Alcohol is an important part of human life and culture. Alcohol abuse is a widespread public health problem globally, causing significant economic burdens in many countries. Therefore, the development of drugs for relieving hangovers and protecting the liver is particularly important. Currently, the application of tetramethylpyrazine and inosine is mostly focused on single-agent research, with few drugs combining the two. Therefore, this invention proposes the application of tetramethylpyrazine combined with inosine in the preparation of drugs for relieving hangovers and protecting the liver, providing a new option for the research and development of such drugs. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide the application of ligustrazine combined with inosine in the preparation of hangover remedies and liver-protecting drugs, thus solving the problems in existing technologies.

[0006] The objective of this invention can be achieved through the following technical solutions: Application of tetramethylpyrazine combined with inosine in the preparation of hangover remedies.

[0007] Application of tetramethylpyrazine combined with inosine in the preparation of drugs for treating alcoholic liver injury.

[0008] Furthermore, the mass ratio of tetramethylpyrazine to inosine is 1:1.5.

[0009] Furthermore, the medication is to be taken orally before and / or after drinking alcohol.

[0010] Furthermore, the dosage of the drug includes: 100-200 mg / kg of tetramethylpyrazine and 150-300 mg / kg of inosine.

[0011] A drug comprising tetramethylpyrazine and inosine.

[0012] Furthermore, the mass ratio of tetramethylpyrazine to inosine is 1:1.5.

[0013] Furthermore, the drug is in the form of powder, tablet, granule, capsule, solution, emulsion, suspension or injection.

[0014] Furthermore, the drug also includes adjuvants, which include one or more of fillers, binders, humectants, disintegrants, and flavoring agents.

[0015] A method for establishing an acute alcohol poisoning mouse model includes: administering 50% alcohol by gavage at a dose of 0.15 ml / 10 g.

[0016] The beneficial effects of this invention are: 1. In this invention, tetramethylpyrazine is an amide alkaloid, and inosine is a common nutrient that is readily available and has no toxic side effects or dependence on the human body.

[0017] 2. This invention innovatively combines tetramethylpyrazine and inosine in the preparation of a hangover-relieving and liver-protecting drug, providing a new option for the development of hangover-relieving and liver-protecting drugs and a new treatment strategy for alcoholic liver injury.

[0018] 3. Through experiments, this invention has found that the combined use of tetramethylpyrazine and inosine can enhance the phosphorylation level of PI3K and AKT proteins by activating the ESR1 / PI3K / AKT signaling pathway and the Nrf2 / HO-1 signaling pathway, reverse the low expression of inflammatory factors IL-10 and the high expression of TNF-α and IL-6, and alleviate the damage of alcohol to the liver in mice. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, for those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 This is a graph showing the behavioral indicators of mice in an experiment investigating the detoxification effect of ligustrazine combined with inosine on mice with acute alcohol poisoning. Figure 2 This is a graph showing the effect of ligustrazine combined with inosine on serum metabolic indicators in mice during an experiment investigating the detoxification effect of acute alcohol poisoning in mice. Figure 3 This is a graph showing the liver index and serum transaminase levels in mice; Figure 4 This is a graph showing the levels of TC and TG in mouse serum; Figure 5 This is a graph showing serum cholesterol levels in mice; Figure 6 This is a graph showing the activity levels of GSH-Px, SOD, and ALDH enzymes in mouse liver. Figure 7 This is a graph showing the gene expression levels of three inflammatory factors in mouse liver tissue; Figure 8 This is a diagram showing the expression levels of major genes in the ESR1 / PI3K / AKT and Nrf2 / HO-1 signaling pathways in mouse liver tissue. Figure 9 This is a graph showing the expression levels of major proteins in the ESR1 / PI3K / AKT and Nrf2 / HO-1 signaling pathways in mouse liver tissue. Figure 10 This is a graph showing the expression levels of major proteins in the ESR1 / PI3K / AKT and Nrf2 / HO-1 signaling pathways in mouse liver tissue. Figure 11 This is a diagram illustrating the mechanism of action of ligustrazine combined with inosine in alcohol detoxification and liver protection. Detailed Implementation

[0021] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] The grouping of the figures in this invention is explained as follows: 1) Blank control group (CG group); 2) Low-dose tetramethylpyrazine gavage group (TMPL group); 3) High-dose tetramethylpyrazine gavage group (TMPH group); 4) Low-dose inosine gavage group (ISL group); 5) High-dose inosine gavage group (high-dose ISH gavage group); 6) Ligustrazine combined with low-dose inosine via gavage (CL group); 7) Group receiving high-dose oral gavage of tetramethylpyrazine combined with inosine (CH group); 8) Silymarin positive control group (PC group).

[0023] In addition, the symbols in all the attached figures are explained as follows: 1) P<0.05 vs CG group; 2) P<0.01 vs CG group; 3) P<0.001 vs CG group; 4) # P<0.05 vs MG group; 5) ## P<0.01 vs MG group; 6) ### P<0.001 vs MG group.

[0024] The tetramethylpyrazine used in the examples has the molecular formula C8H12N2, and its structural formula is as follows: The molecular formula of inosine is C10H12N4O5, and the structural formula of inosine is as follows: Example 1 In this embodiment, the detoxifying effect of tetramethylpyrazine combined with inosine on mice with acute alcohol poisoning was verified.

[0025] 1. Laboratory animals SPF-grade healthy male ICR mice (15-19g) were selected and provided by Jiangsu Qinglongshan Biotechnology Co., Ltd. The experimental animals were housed in an SPF animal laboratory at a temperature of 20℃-26℃ and a relative humidity of 40%-70%. The rearing cycle was repeated every 12 hours, with 4-5 mice per cage. All mice had free access to water and food.

[0026] 2. Experimental Methods All 80 mice were fed a standard experimental maintenance diet. After one week of acclimatization, the mice were randomly divided into 8 groups: blank control group (CG group), low-dose tetramethylpyrazine gavage group (TMPL group), high-dose tetramethylpyrazine gavage group (TMPH group), low-dose inosine gavage group (ISL group), high-dose inosine gavage group (ISH high-dose inosine gavage group), tetramethylpyrazine combined with low-dose inosine gavage group (CL group), tetramethylpyrazine combined with high-dose inosine gavage group (CH group), and silymarin positive control group (PC group), with 10 mice in each group. The mice were first given a 14-day prophylactic gavage treatment, with the gavage dosage and grouping settings shown in Table 1.

[0027] Table 1. Grouping of mice in the experiment investigating the detoxifying effect of tetramethylpyrazine combined with inosine on mice with acute alcohol poisoning. Establishing an acute alcohol poisoning mouse model requires a single large dose of alcohol administered via gavage. This experiment used 50% alcohol at a dose of 0.15 ml / 10 g to construct the mouse model. On day 15, all eight groups of mice underwent their first single large-dose gavage of 50% (v / v) alcohol at 0.15 ml / 10 g. Data on intoxication time, sobering-up time, and attachment time were collected from different gavage groups. After a 48-hour washout period, mice were given a prophylactic gavage for 7 days at the same dose and grouping. On day 26, all eight groups of mice underwent another single acute alcohol gavage at the same dose as on day 15. Blood was then collected from the mice, and serum metabolic indicators were analyzed to determine the antidote effects of tetramethylpyrazine and inosine alone and in combination on acute alcohol poisoning in mice.

[0028] 3. Experimental Results (1) Effects of prophylactic gavage administration of tetramethylpyrazine and inosine on the post-alcohol state and behavior of mice Effects of tetramethylpyrazine combined with inosine on the post-alcohol state and behavior of mice, such as Figure 1 As shown, Figure 1 (A) in the figure reflects the time of intoxication in mice after gavage; Figure 1 (B) in the figure reflects the sobering time of mice after gavage; Figure 1 (C) in the figure reflects the attachment time of mice after gavage.

[0029] The results showed that prophylactic gavage administration of tetramethylpyrazine or inosine alone had no significant effect on the behavioral changes of mice after alcohol consumption. However, combined prophylactic gavage administration of tetramethylpyrazine and inosine had some effect on the duration of intoxication, sobering-up time, and climbing time in mice. Specifically, it significantly increased the duration of intoxication, decreased the sobering-up time, and increased the climbing time in mice.

[0030] Regarding the duration of intoxication, the duration of intoxication was significantly longer in the CL and CH groups compared to the CG group, indicating that the combined use of tetramethylpyrazine and inosine can delay the onset of alcohol poisoning. Regarding sobering-up time, the sobering-up time was significantly shorter in both the low-dose and high-dose groups of the tetramethylpyrazine and inosine combination, indicating that it can alleviate the sedative effect of alcohol. Regarding adhesion time, the adhesion time was also significantly shorter in both the low-dose and high-dose groups of the tetramethylpyrazine and inosine mixture. These experimental results demonstrate that the combined use of tetramethylpyrazine and inosine does indeed have certain potential efficacy in relieving alcohol intoxication.

[0031] (2) Effects of prophylactic gavage administration of tetramethylpyrazine and inosine on serum metabolic indicators in mice after alcohol consumption Effects of prophylactic gavage administration of tetramethylpyrazine and inosine on serum metabolic parameters in mice after alcohol consumption, such as Figure 2 As shown, Figure 2 (A) in the figure reflects the blood ethanol level; Figure 2(B) in the figure reflects serum ADH levels; Figure 2 (C) in the figure reflects serum ALDH levels; Figure 2 (D) in the figure reflects serum 5-HT levels.

[0032] The results showed that the serum ethanol (EtOH) levels in the intervention group were lower than those in the CG group. However, only the high-dose and low-dose groups of tetramethylpyrazine and inosine showed statistically significant differences from the CG group. The high-dose group of tetramethylpyrazine and inosine showed the most significant decrease, indicating the best alcohol metabolism function, even better than the effect of silymarin in the positive control group.

[0033] The high-dose group of tetramethylpyrazine and inosine combination therapy showed a significant increase in alcohol dehydrogenase (ADH), with a statistically significant difference compared to the CG group and essentially the same as the positive control group. Both the high-dose group of tetramethylpyrazine and inosine monotherapy and the combination therapy group showed significant increases in aldehyde dehydrogenase (ALDH), with statistically significant differences compared to the CG group and essentially the same as the positive control group. Furthermore, the high-dose combination therapy group showed the best efficacy.

[0034] The degree of liver damage can be indirectly reflected by comparing the levels of serotonin (5-HT) in the blood of mice. In this experiment, the combined administration of tetramethylpyrazine and inosine showed a more significant increase in 5-HT compared to the CG group, while the positive control group showed the best results.

[0035] Example 2 In this embodiment, the alleviating effect of tetramethylpyrazine combined with inosine on alcoholic liver injury in mice was verified.

[0036] 1. Laboratory animals SPF-grade healthy male ICR mice (15-19g) were selected and provided by Hangzhou Medical College. The experimental animals were housed in an SPF animal laboratory at a temperature of 20℃-26℃ and a relative humidity of 40%-70%. The rearing cycle was repeated every 12 hours, with 4-5 mice per cage. All mice had free access to water and food.

[0037] 2. Experimental Methods This experiment used a liquid alcohol diet to establish a mouse model of alcoholic liver injury to compare the alleviating effects of single and combined gavage administration of tetramethylpyrazine and inosine on mice with alcoholic liver injury. The liquid alcohol diet was purchased from Jiangsu Xietong Pharmaceutical Biotechnology Co., Ltd. The liquid alcohol diet was changed daily during the treatment period to ensure sufficient food intake for the mice. Since the diet was liquid alcohol, no additional water was required for the mice.

[0038] Ninety mice were acclimatized to a standard diet for one week. The mice were then randomly divided into nine groups: a blank control group (CG group), a model control group (MG group), a low-dose tetramethylpyrazine gavage group (TMPL group), a high-dose tetramethylpyrazine gavage group (TMPH group), a low-dose inosine gavage group (ISL group), a high-dose inosine gavage group (ISH high-dose inosine gavage group), a tetramethylpyrazine combined with low-dose inosine gavage group (CL group), a tetramethylpyrazine combined with high-dose inosine gavage group (CH group), and a silymarin positive control group (PC group). Each group consisted of 10 mice. The mice were administered the gavage daily, and the grouping and dosage settings are shown in Table 2. Table 2. Grouping of mice in the experiment investigating the alleviating effect of tetramethylpyrazine combined with inosine on alcoholic liver injury in mice. 3. Experimental Results (1) Effects of tetramethylpyrazine combined with inosine on liver index and serum transaminase levels in mice with alcoholic liver injury; The liver index, which is the ratio of a mouse's liver weight to its body weight, can be used to assess liver health. Figure 3 As shown, the liver index of the model group mice was significantly higher than that of the normal control group. Compared with the model group, the high-dose gavage group of tetramethylpyrazine combined with inosine could significantly reduce the increase in liver index of mice caused by alcoholic liquid diet and narrow the difference with the blank control group.

[0039] The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum of experimental mice were measured, and the results are as follows: Figure 3 As shown, Figure 3 (A) in the chart reflects the liver index; Figure 3 (B) in the table reflects serum ALT levels; Figure 3 (C) in the figure reflects serum AST levels. It can be seen that the ALT and AST enzyme activities in the model group MG mice were higher than those in the blank control group, and the difference was statistically significant. ALT and AST are clinically sensitive indicators of liver damage, indicating that the liver of mice was damaged after being fed an alcoholic liquid diet, thus establishing an alcoholic liver injury (ALI) model. Furthermore, after administering tetramethylpyrazine and inosine to mice via gavage, both ALT and AST transaminases decreased to varying degrees, with the group receiving tetramethylpyrazine combined with inosine showing the most significant effect.

[0040] (2) Effects of tetramethylpyrazine combined with inosine on blood lipid levels in mice with alcoholic liver injury; The accumulation of total cholesterol (TC) and triglycerides (TG) typically occurs in the early stages of liver disease and can induce fatty liver. In this experiment, the results were as follows: Figure 4 As shown, Figure 4 (A) in the table reflects serum TC levels.Figure 4 (B) reflects serum TG levels. It can be seen that alcohol intake significantly increased serum TC and TG levels in mice. Single administration of tetramethylpyrazine and inosine, as well as combined administration of tetramethylpyrazine and inosine, can reduce blood lipid levels in ALI mice to some extent, and the degree of lipid reduction is dose-dependent with respect to the intervention. This indicates that at appropriate concentrations, tetramethylpyrazine and inosine can alleviate liver damage in mice by reducing blood lipids.

[0041] (3) Effects of tetramethylpyrazine combined with inosine on serum cholesterol levels in mice with alcoholic liver injury; High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are important indicators of serum cholesterol levels, and their levels are closely related to the severity of liver disease. In this experiment, the cholesterol levels of mice after intervention were as follows: Figure 5 As shown, Figure 5 (A) in the figure reflects serum HDL-C levels; Figure 5 (B) in the figure reflects serum LDL-C levels. It can be seen that the HDL-C level in the model group (MG group) was significantly lower than that in the blank control group (CG), while the LDL-C level was significantly higher, indicating that alcohol intake can also lead to disordered serum cholesterol levels in mice. Intervention with tetramethylpyrazine and inosine can alleviate the decrease in HDL-C and the increase in LDL-C in ALI mice, and the combined gavage group showed better results than the single gavage group. This demonstrates that administering tetramethylpyrazine and inosine to mice via gavage can regulate their serum cholesterol levels, thereby alleviating alcohol-induced liver damage.

[0042] (4) Effects of tetramethylpyrazine combined with inosine on the activity levels of related enzymes in the liver tissue of mice with alcoholic liver injury; GSH-Px is a crucial peroxidase in the body, while SOD is an indispensable antioxidant metalloenzyme; both are important indicators of the body's resistance to peroxidation. ALDH plays a vital role in the metabolism of ethanol, metabolizing it in mice and thus mitigating the harmful effects of ethanol on them. The results of this experiment are as follows... Figure 6 As shown, Figure 6 (A) reflects the level of GSH-Px in liver tissue; Figure 6 (B) reflects the SOD level in liver tissue; Figure 6(C) in the figure reflects the ALDH level in liver tissue. It can be seen that the activities of GSH-Px, SOD, and ALDH enzymes in the model group (MG group) were significantly reduced compared to the blank control group (CG group). Gavage administration of tetramethylpyrazine and inosine to mice increased the activities of these three enzymes in a dose-dependent manner. The combined gavage administration of tetramethylpyrazine and inosine showed a more significant effect than that of either alone, indicating that tetramethylpyrazine and inosine can alleviate the liver damage caused by alcohol intake in mice by increasing the activity of antioxidant enzymes in liver tissue.

[0043] Example 3 In this embodiment, the mechanism by which ligustrazine combined with inosine alleviates alcoholic liver injury in mice in Example 2 is analyzed.

[0044] (1) Effects of tetramethylpyrazine combined with inosine on inflammatory factors in liver tissue of mice with alcoholic liver injury; The gene expression of three inflammatory factors, TNF-α, IL-6, and IL-10, in mouse liver tissue is as follows: Figure 7 As shown, Figure 7 (A) in the figure reflects the expression level of the TNF-α gene; Figure 7 (B) in the figure reflects the expression level of the IL-6 gene; Figure 7 (C) in the figure reflects the expression level of the IL-10 gene. It can be seen that compared with the CG group mice, the levels of inflammatory factors TNF-α and IL-6 in the liver tissue of mice modeled with alcoholic liquid diet were significantly increased, while the level of inflammatory factor IL-10 was significantly decreased, and the differences were statistically significant. The levels of TNF-α and IL-6 in each intervention group treated with different doses of tetramethylpyrazine and inosine were decreased, with the combined gavage group showing a greater decrease in these two indicators than the single intervention group, and the differences were statistically significant compared with the MG group. Similarly, the increase in the level of inflammatory factor IL-10 relative to the model group was also better in the combined gavage group than in the single gavage group. In summary, combined intervention with a certain dose of tetramethylpyrazine and inosine can significantly reduce the levels of TNF-α and IL-6 in the liver tissue of alcohol-induced ALI mice and increase the level of IL-10, thereby alleviating the damage caused by the inflammatory response.

[0045] (2) Effects of tetramethylpyrazine combined with inosine on the expression of major genes in the ESR1 / PI3K / AKT signaling pathway and Nrf2 / HO-1 signaling pathway in liver tissue of mice with alcoholic liver injury; The expression of major genes in the PI3K / AKT signaling pathway and the Nrf2 / HO-1 signaling pathway in mouse liver tissue is as follows: Figure 8 As shown, Figure 8 (A) in the figure reflects the expression level of the ESR1 gene; Figure 8 (B) in the figure reflects the expression level of the AKT gene;Figure 8 (C) in the figure reflects the expression level of the PI3K gene; Figure 8 (D) in the figure reflects the expression level of the Nrf2 gene; Figure 8 (E) in the figure reflects the expression level of the OH-1 gene. It can be seen that compared to the CG group mice, the mRNA expression levels of ESR1, AKT, PI3K, Nrf2, and OH-1 in the liver tissue of the MG group mice were significantly decreased. However, after intervention with tetramethylpyrazine and inosine, the mRNA expression levels of ESR1, AKT, PI3K, Nrf2, and OH-1 in the liver tissue of mice in both the single-dose and combined-dose groups increased. It is noteworthy that the single-dose groups were less effective than the combined-dose groups. Furthermore, except for the low-dose inosine gavage group, which showed better results than the high-dose group, the low-dose single-dose groups in all groups did not show a significant increase in the mRNA expression of ESR1, AKT, PI3K, Nrf2, and OH-1 compared to the high-dose gavage group, and there was no significant difference compared to the MG group. Therefore, it can be inferred that within a certain dosage range, the intervention effects of tetramethylpyrazine and inosine are dose-related, which is basically consistent with the results of the mouse serum and liver tissue indicators mentioned above.

[0046] (3) Effects of tetramethylpyrazine combined with inosine on the expression of major proteins in the ESR1 / PI3K / AKT signaling pathway and Nrf2 / HO-1 signaling pathway in liver tissue of mice with alcoholic liver injury; The expression of major proteins in the ESR1 / PI3K / AKT signaling pathway and the Nrf2 / HO-1 signaling pathway in mouse liver are as follows: Figure 9 and Figure 10 As shown; where, Figure 10 (A) in the figure reflects the expression level of PI3K protein; Figure 10 (B) in the figure reflects the expression level of Nrf2 protein; Figure 10 (C) in the figure reflects the expression level of AKT protein; Figure 10 (D) in the figure reflects the expression level of ESR1 protein; Figure 10 (E) in the figure reflects the expression level of OH-1 protein. Considering the overall modeling effect, the expression levels of PI3K, Nrf2, AKT, ESR1, and HO-1 proteins in the MG group all decreased significantly, with meaningful differences, consistent with their gene expression levels. After intervention with tetramethylpyrazine and inosine, the protein levels in both the single gavage group and the combined gavage group increased. The overall trend of protein expression levels was basically the same as that of gene expression, except for minor differences.

[0047] In summary, this invention evaluated the effects of tetramethylpyrazine combined with inosine administration on post-alcohol status, behavior, and metabolic indicators using a single excessive alcohol intake animal model. It also evaluated the effects of tetramethylpyrazine combined with inosine administration on liver index, blood lipid levels, serum cholesterol levels, serum transaminase levels, and liver-related enzyme activity in mice using a liquid alcohol diet model of alcoholic liver injury. These findings confirm that tetramethylpyrazine combined with inosine has a detoxifying and liver-protective effect. Figure 11 As shown, mechanistic studies revealed that the combined use of tetramethylpyrazine and inosine can enhance the activity of hepatic SOD, GSH-Px, and ALDH enzymes, increase antioxidant capacity, and regulate lipid metabolism by modulating the expression of genes and proteins in the ESR1, PI3K / AKT, and Nrf2 / HO-1 signaling pathways, thereby improving fat accumulation, reducing the levels of pro-inflammatory factors such as TNF-α and IL-6, increasing the level of the anti-inflammatory factor IL-10, and alleviating symptoms of alcoholic liver injury in mice. The combined administration was more effective than the single-drug group, and showed a dose-related relationship when the interventions were the same.

[0048] In the description of this specification, references to terms such as "an embodiment," "example," "specific example," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0049] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the claimed invention.

Claims

1. Application of tetramethylpyrazine combined with inosine in the preparation of hangover remedies.

2. Application of tetramethylpyrazine combined with inosine in the preparation of drugs for treating alcoholic liver injury.

3. The application according to claim 1 or 2, characterized in that, The mass ratio of tetramethylpyrazine to inosine is 1:1.

5.

4. The application according to claim 1 or 2, characterized in that, The medication is to be taken orally before and / or after drinking alcohol.

5. The application according to claim 4, characterized in that, The dosage of the drug includes: 100-200 mg / kg of ligustrazine and 150-300 mg / kg of inosine.

6. A drug, characterized in that, Including tetramethylpyrazine and inosine.

7. The drug according to claim 6, characterized in that, The mass ratio of tetramethylpyrazine to inosine is 1:1.

5.

8. The drug according to claim 6, characterized in that, The drug is in the form of powder, tablet, granule, capsule, solution, emulsion, suspension or injection.

9. The drug according to claim 6, characterized in that, The drug also includes adjuvants, which include one or more of fillers, binders, disintegrants, lubricants, and flavoring agents.

10. A method for constructing a mouse model of acute alcohol poisoning, characterized in that, The method includes: administering 50% alcohol by gavage at a dose of 0.15 ml / 10 g.

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