Application of ribavirin and / or zanamivir in preparation of medicine for dispelling effects of alcohol and / or preventing drunkenness

Abstract

The invention relates to the technical field of medicine, in particular to application of ribavirin and / or zanamivir in preparation of a medicine for dispelling the effects of alcohol and / or preventing drunkenness, ribavirin and zanamivir can remarkably prolong the time needed by righting reflex disappearance of a mouse and shorten the time needed by righting reflex recovery of the mouse at a lower administration dosage, and the effect of ribavirin and zanamivir on dispelling the effects of alcohol and / or preventing drunkenness is achieved. The effect of inhibiting lethal of alcohol, which is the same as that of a positive control group RU21 Annaopu composite tablet, is achieved with a lower administration dosage, which indicates that the ribavirin and the zanamivir have the effects of preventing drunkenness, accelerating sobering and inhibiting lethal of alcohol.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to the use of ribavirin and / or zanamivir in preparing a drug for treating hangover and / or preventing drunkenness. Background Art

[0002] Alcohol consumption is closely linked to various types of cancer, cardiovascular disease, cirrhosis, dementia, infectious diseases (such as tuberculosis and pneumonia), and other illnesses. Alcohol consumption can lead to emotional instability, confusion, decreased control and memory, abnormal behavior, and sensitivity to external stimuli. Excessive drinking at one time can cause the drinker to fall into a coma, making it difficult to regain consciousness or control their speech and behavior within a short period of time. This can put the safety of life and property at risk, and can also cause coma or even death due to profound central nervous system depression.

[0003] Currently, most hangover remedies in my country are based on natural medicines or traditional Chinese medicine compositions. For example, invention patent CN115299614A discloses a hangover remedy composition comprising the following components by weight: 1-8 parts corn oligopeptides, 0.5-2.5 parts Amomum villosum, 0.5-2.5 parts Tremella fuciformis polysaccharide, 0.1-1 parts taurine, 0.1-1 parts Lablab dalbergiae, 0.1-0.8 parts Phyllanthus emblica extract, 0.05-0.5 parts Camellia sinensis extract, 0.05-0.5 parts gamma-aminobutyric acid, and 0.05-0.5 parts Ampelopsis glauca leaf extract. Invention patent CN106492110B discloses a hangover remedy composition comprising the following components: maca extract, kudzu root extract, turmeric extract, and Hovenia dulcis fruit extract. Invention patent CN115429790B discloses the use of isoflavone compounds in the preparation of a drug for preventing or treating alcoholic liver damage or for alcohol detoxification and liver protection. However, the composition disclosed in the aforementioned patent is still in the research and development stage and needs to undergo clinical trial approval before it can enter the market. As is well known to those skilled in the art, clinical trial approval for drugs can take a long time and cannot be put into use immediately.

[0004] Repurposing old drugs for new uses is a current research hotspot. If a new clinical drug use is discovered, it can be put into clinical trials quickly, significantly reducing R&D costs and time. Ribavirin is a nucleotide analog and a broad-spectrum nucleoside antiviral drug with inhibitory effects against a variety of RNA and DNA viruses. It is widely used clinically to treat diseases such as influenza, measles, hepatitis A, hemorrhagic fever, herpes zoster, and viral encephalitis. Zanamivir is a purine derivative that inhibits viral protein synthesis, thereby preventing viral replication and infection. It is clinically used to treat viral infections such as hepatitis B virus, hepatitis C virus, and HIV.

[0005] During the experiment, the inventor accidentally discovered that ribavirin and zanamivir have the function of preventing alcohol intolerance, alcohol intoxication, alcohol poisoning and accelerating sobering up, which provides new uses for ribavirin and zanamivir. Summary of the Invention

[0006] In view of the above problems, the primary purpose of the present invention is to provide the use of ribavirin and its pharmaceutically acceptable salts in the preparation of a drug for treating alcohol detoxification.

[0007] The second object of the present invention is to provide the use of zanamivir and its pharmaceutically acceptable salts in the preparation of a drug for treating hangover.

[0008] The third object of the present invention is to provide the use of ribavirin and its pharmaceutically acceptable salts in the preparation of drugs for preventing drunkenness.

[0009] The fourth object of the present invention is to provide the use of zanamivir and its pharmaceutically acceptable salts in the preparation of drugs for preventing drunkenness.

[0010] A fifth object of the present invention is to provide the use of ribavirin and / or zanamivir and pharmaceutically acceptable salts thereof in the preparation of a medicament for treating and / or preventing alcohol poisoning, alcohol-induced death or complications of drinking.

[0011] Preferably, the drug further comprises a pharmaceutically acceptable carrier.

[0012] Preferably, the drug is added with pharmaceutically acceptable excipients to be prepared into powders, tablets, granules, capsules, solutions, emulsions, suspensions, and injections.

[0013] Preferably, the medicine is taken before and / or after drinking alcohol.

[0014] The beneficial effects of the present invention are as follows: the present invention provides a new use of ribavirin and zanamivir in the preparation of a drug with the effects of preventing drunkenness and sobering up; the ribavirin and zanamivir can significantly prolong the time required for the disappearance of the righting reflex in mice and shorten the time required for the recovery of the righting reflex in mice at a lower dosage; and the same effect of inhibiting alcohol-induced lethality as that of the positive control group, RU21 Antipol compound tablets, is achieved at a lower dosage, indicating that ribavirin and zanamivir have the effects of preventing drunkenness, accelerating sobering up, and inhibiting alcohol-induced lethality. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The present invention provides a histogram of the time required for the righting reflex to disappear in each drug-treated group of mice;

[0016] Note: "Control" refers to the blank control group without alcohol intervention; "Model" refers to the model control group after a single alcohol overdose intervention; "RU21" refers to the positive control group receiving RU21 Antipu combined tablets; and "Ribavirin" refers to the ribavirin group. Compared with the model group receiving a single alcohol overdose intervention, p > 0.05; compared with the positive control group receiving RU21 Antipu combined tablets, p > 0.05. Control group: n = 6; Model group: n = 9; RU21 group: n = 12; Ribavirin group: n = 12; the dose was 90 mg / kg. All data were analyzed using one-way analysis of variance.

[0017] Figure 2 The present invention provides a bar graph of the time required for the righting reflex to recover in each drug-treated group of mice;

[0018] Note: "Control" refers to the group not receiving alcohol treatment, "Model" refers to the control group for the single-dose alcohol overdose model, "RU21" refers to the positive control group receiving RU21 Antipu combined tablets, and "Ribavirin" refers to the ribavirin group. *p < 0.05 compared with the single-dose alcohol overdose model group; p > 0.05 compared with the positive control group receiving RU21 Antipu combined tablets. Control group: n = 6; Model group: n = 7; RU21 group: n = 8; Ribavirin group: n = 10; the dose was 90 mg / kg. All data were analyzed using one-way analysis of variance.

[0019] Figure 3 The present invention provides a histogram of the survival rate of mice in each drug administration group 24 hours after drinking;

[0020] Note: "Control" refers to the group without alcohol intervention, "Model" refers to the control group for the single-dose alcohol intervention model, "RU21" refers to the positive control group receiving RU21 Antipu compound tablets, and "Ribavirin" refers to the ribavirin group. Control group: n = 6; Model group: n = 12; RU21 group: n = 12; Ribavirin group: n = 12, with a dose of 90 mg / kg. All data were analyzed using one-way analysis of variance.

[0021] Figure 4 The present invention provides a histogram of the time required for the righting reflex to disappear in each drug-treated group of mice;

[0022] Note: "Control" represents the blank control group without alcohol intervention; "Model" represents the model control group after a single alcohol overdose intervention; "RU21" represents the positive control group receiving RU21 antamid combined tablets; and "Zanamivir" represents the zanamivir group. **p < 0.01 compared with the model group receiving a single alcohol overdose intervention; *p < 0.05 compared with the positive control group receiving RU21 antamid combined tablets. Control group: n = 3; Model group: n = 3; RU21 group: n = 3; Zanamivir group: n = 4; dose was 8 mg / kg. All data were analyzed using one-way analysis of variance.

[0023] Figure 5 The present invention provides a bar graph of the time required for the righting reflex to recover in each drug-treated group of mice;

[0024] Note: "Control" refers to the group not receiving alcohol intervention, "Model" refers to the control group for the single-dose alcohol intervention model, "RU21" refers to the positive control group receiving RU21 Activin combination tablets, and "Zanamivir" refers to the zanamivir group. Compared with the positive control group receiving RU21 Activin combination tablets, p>0.05. Control group: n=3; Model group: n=3; RU21 group: n=2; Zanamivir group: n=4; dose was 8 mg / kg. All data were analyzed using one-way analysis of variance.

[0025] Figure 6 The present invention provides a histogram of the mortality rate of mice in each drug administration group 24 hours after drinking;

[0026] Note: "Control" refers to the group not receiving alcohol treatment, "Model" refers to the control group for the single-dose alcohol overdose model, "RU21" refers to the positive control group receiving RU21 Activin combination tablets, and "Zanamivir" refers to the zanamivir group. Control group: n = 3; Model group: n = 3; RU21 group: n = 3; Zanamivir group: n = 4; the dose was 8 mg / kg. All data were analyzed using one-way analysis of variance. DETAILED DESCRIPTION

[0027] The following will provide a clear and complete description of the technical solutions in the examples of the present invention, in conjunction with the accompanying drawings. It is clear that the described embodiments are only a portion of the embodiments of the present invention, not all of them. The invention also protects the therapeutic effects of ribavirin and zanamivir on all symptoms following alcohol intervention, including different dosage forms and dosages. Based on the embodiments of the present invention, all other embodiments derived by persons of ordinary skill in the art without inventive effort are intended to fall within the scope of protection of the present invention.

[0028] It should be understood that the above summary and the following detailed description are exemplary and explanatory only and do not limit the subject matter of the present invention in any way. In this application, it must be noted that unless otherwise clearly indicated, the singular forms used in this specification and claims include the plural forms of the referents. It should also be noted that unless otherwise indicated, the use of "or" and "or" means "and / or". In addition, the use of the term "including" and other forms, such as "comprising", "including" and "containing" are not limiting.

[0029] The "RU21 Antipu Composite Tablets" described in the present invention are produced by Spirit Sciences of the United States and are now a well-known hangover relieving product in the world.

[0030] Example 1: Study on the Effect of Ribavirin in Preventing Drunkenness, Accelerating Sobering and Inhibiting Alcohol-Induced Death

[0031] 1. Experimental Animals

[0032] Clean-grade female Kunming mice weighing 22 ± 2 g were used. They were provided by the Laboratory Animal Facility of Lanzhou University. They did not receive any medication prior to the experiment. The animals were acclimated for one week in an environment with a temperature of 20–25°C and a 12-hour day / night cycle. They were provided with free access to food and water before being divided into groups for the experiment.

[0033] 2. Drugs and reagents

[0034] Ribavirin tablets were purchased from Shandong Qidu Pharmaceutical Co., Ltd., batch number: 1D2307013, molecular weight: 244.21;

[0035] RU21 Antipro compound tablets were purchased from Spirit Science USA, lot number: 90045;

[0036] Anhydrous ethanol was purchased from Tianjin Fuyu Fine Chemical Co., Ltd., batch number: May 8, 2023.

[0037] 3. Experimental Grouping and Oral Administration Dosage

[0038] Forty-two female Kunming mice were randomly divided into four groups: blank control group (Control), model control group (Model), positive control group (RU21), and ribavirin group (Ribavirin). Except for the blank control group which contained 6 mice, the other groups each contained 12 mice.

[0039] 4. Experimental Methods

[0040] Forty-two Kunming mice were grouped as described above. After a 12-hour fast before the experiment, the blank control group (Control) and the model group (Model) were gavaged with an equal volume of normal saline. The positive control group (RU21) was gavaged with RU21 Aspirin tablets at a dose of 500 mg / kg, and the ribavirin group (Ribavirin) was gavaged with 90 mg / kg of ribavirin. Thirty minutes after gavage, except for the blank control group, which was gavaged with an equal volume of double-distilled water, the other three groups were gavaged with 60% alcohol at a dose of 0.18 mL / 10 g. Immediately, a timer was started, and the time required for the righting reflex to disappear and the time required for the righting reflex to recover, as well as the survival rate of each group within 24 hours after alcohol administration, were recorded and calculated.

[0041] 5. Experimental Results

[0042] (1) The time required for the mouse's righting reflex to disappear

[0043] like Figure 1 As shown, compared with the blank control group, the time required for the righting reflex to disappear in the model group mice was shorter, which is consistent with the model of drunkenness after a single excessive drinking, indicating that the model was successfully established. Compared with the positive control group, the time required for the righting reflex to disappear in the ribavirin group was prolonged by ribavirin, which was not significantly different from the positive control RU21 Antipu compound tablet group (p>0.05), indicating that ribavirin and the positive control RU21 Antipu compound tablets have the same effect in preventing drunkenness. However, in this experiment, the positive control group was administered at a dose of 500 mg / kg, while the ribavirin group was administered at a dose of 90 mg / kg, which was 18% of the dose of the positive control group. In other words, ribavirin achieved the same effect in preventing drunkenness as the positive control RU21 Antipu compound tablet at a lower dose.

[0044] (2) Time required for mice to recover their righting reflex

[0045] like Figure 2 As shown, compared with the positive control group, ribavirin shortened the time required for the recovery of the righting reflex in mice, which was not significantly different from the positive control RU21 Antipu compound tablet group (p>0.05), indicating that ribavirin and the positive control RU21 Antipu compound tablet have the same effect of accelerating sobering up. In this experiment, the positive control group was administered at a dose of 500 mg / kg, and the ribavirin group was administered at a dose of 90 mg / kg, which was 18% of the dose of the positive control group. In other words, ribavirin achieved the same effect of accelerating sobering up as the positive control RU21 Antipu compound tablet at a lower dose.

[0046] (3) Survival rate of mice in each group within 24 hours after drinking

[0047] like Figure 3As shown, compared with the model group, ribavirin has an inhibitory effect on alcohol-induced lethality within 24 hours after drinking. Compared with the positive control group, the survival rate of mice in the ribavirin group within 24 hours after drinking was 83.33%, while the survival rate of mice in the positive control group was 66.67%. However, in this experiment, the positive control group was administered a dose of 500 mg / kg, while the ribavirin group was administered a dose of 90 mg / kg, which is 18% of the positive control group's dose. In other words, ribavirin achieved the same inhibitory effect on alcohol-induced lethality as the positive control RU21 Antipro combination tablets at a lower dose.

[0048] Example 2: Study on the Effect of Zanamivir on Preventing Drunkenness, Accelerating Sobering and Inhibiting Alcohol-Induced Death

[0049] 1. Experimental Animals

[0050] Clean-grade female Kunming mice weighing 20 ± 2 g were used. They were provided by the Laboratory Animal Facility of Lanzhou University. They did not receive any medication prior to the experiment. The animals were acclimated for one week in an environment with a temperature of 20–25°C and a 12-hour day / night cycle. They were provided with free access to food and water before being divided into groups for the experiment.

[0051] 2. Drugs and reagents

[0052] Zanamivir was purchased from Shanghai Myrel Biochemical Technology Co., Ltd., batch number: 139110808, molecular weight: 332.31;

[0053] RU21 Antipro compound tablets were purchased from Spirit Science USA, batch number: 90274;

[0054] Anhydrous ethanol was purchased from Tianjin Fuyu Fine Chemical Co., Ltd., batch number: May 8, 2023.

[0055] 3. Experimental Grouping and Oral Administration Dosage

[0056] Thirteen female Kunming mice were randomly divided into four groups: blank control group (Control), model control group (Model), positive control group (RU21), and zanamivir group (Zanamivir). Except for the zanamivir group which had four mice, the other groups each contained three mice.

[0057] 4. Experimental Methods

[0058] Thirteen Kunming mice were grouped as described above. After a 12-hour fast before the experiment, the blank control group (Control) and the model group (Model) were gavaged with an equal volume of normal saline. The positive control group (RU21) was gavaged with 500 mg / kg of RU21 Aspirin tablets, and the zanamivir group was gavaged with 8 mg / kg of zanamivir. Thirty minutes after gavage, except for the blank control group, which was gavaged with an equal volume of double-distilled water, the other three groups were gavaged with 0.10 mL / 10 g of 60% alcohol. Immediately, a timer was started, and the duration of loss and recovery of the righting reflex in each group was recorded.

[0059] 5. Experimental Results

[0060] (1) The time required for the mouse's righting reflex to disappear

[0061] like Figure 4 As shown, compared with the blank control group, the time required for the righting reflex to disappear in the model group was shorter, consistent with a model of intoxication after a single excessive alcohol intake, indicating that the model was successfully established. Compared with the model group, the zanamivir group significantly prolonged the time required for the righting reflex to disappear in the mice (**p < 0.01), indicating that zanamivir has a preventive effect on intoxication. Compared with the positive control RU21 Antipu compound tablet group, the zanamivir group significantly prolonged the time required for the righting reflex to disappear in the mice (*p < 0.05), indicating that zanamivir is more effective in preventing intoxication than the RU21 Antipu compound tablet.

[0062] (2) Time required for mice to recover their righting reflex

[0063] like Figure 5 As shown, compared with the positive control group, zanamivir shortened the time required for mice to recover their righting reflex, with no significant difference from the positive control RU21 ANTIPLE combination tablet group (p>0.05), indicating that ribavirin and the positive control RU21 ANTIPLE combination tablets have the same effect in accelerating hangover recovery. In this experiment, the positive control group was administered a dose of 500 mg / kg, while the zanamivir group was administered a dose of 8 mg / kg, which is 1.6% of the positive control group's dose. In other words, zanamivir achieved the same effect of accelerating hangover recovery as the positive control RU21 ANTIPLE combination tablet at a lower dose.

[0064] (3) Survival rate of mice in each group within 24 hours after drinking

[0065] like Figure 6As shown, compared with the model group, zanamivir had the effect of inhibiting alcohol-induced lethality within 24 hours after drinking; compared with the positive control RU21 Antipu compound tablet group, within 24 hours after drinking, the survival rate of mice in the zanamivir group was 100%, and the survival rate of mice in the positive control group was 66.67%.

[0066] In summary, the present invention provides a novel use of ribavirin and zanamivir in the preparation of a drug with the efficacy of preventing intoxication and sobering up. The ribavirin and zanamivir can significantly prolong the time required for the loss of the righting reflex in mice and shorten the time required for the recovery of the righting reflex in mice at a lower dosage. The same effect of inhibiting alcohol-induced mortality as the positive control group RU21 Antipol compound tablets is achieved at a lower dosage, indicating that ribavirin and zanamivir have the effects of preventing intoxication, accelerating sobering up, and inhibiting alcohol-induced mortality.

[0067] Any technical solutions obtained by technicians through logical analysis, inference and experimentation based on the existing technology in accordance with the ideas of the present invention shall fall within the scope of protection of the claims.

Claims

1. Use of ribavirin and its pharmaceutically acceptable salts in the preparation of a drug for treating hangover.

2. Use of zanamivir and its pharmaceutically acceptable salts in the preparation of drugs for treating hangover.

3. Use of ribavirin and its pharmaceutically acceptable salts in the preparation of drugs for preventing drunkenness.

4. Use of zanamivir and its pharmaceutically acceptable salts in the preparation of drugs for preventing drunkenness.

5. Use of ribavirin and / or zanamivir and pharmaceutically acceptable salts thereof in the preparation of a medicament for treating and / or preventing alcohol poisoning, alcohol-induced death or complications of drinking.

6. The use according to any one of claims 1 to 5, characterized in that The medicine also includes a pharmaceutically acceptable carrier.

7. The use according to claim 6, characterized in that The drug is added with pharmaceutically acceptable excipients to be prepared into powders, tablets, granules, capsules, solutions, emulsions, suspensions and injections.

8. The use according to any one of claims 1 to 5, characterized in that The medicine is taken before and / or after drinking alcohol.

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