Use of ergothioneine in accelerating alcohol metabolism and / or preventing or alleviating hangover

Abstract

A method and composition for accelerating alcohol metabolism and / or preventing or alleviating a hangover, and a related use thereof in the preparation of foods, beverages, nutritional supplements, and animal feeds for accelerating alcohol metabolism. The composition comprises an effective amount of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analogue or derivative thereof, and can also optionally comprise an effective amount of paraxanthine or 1-methylxanthine.

Description

Ergothioneine for hangover relief and / or prevention or amelioration of after-hangover TECHNICAL FIELD

[0001] The present invention belongs to the technical field of dietary or nutritional supplements, in particular to a method and composition for hangover relief and / or prevention or amelioration of after-hangover and its related application in the preparation of food, beverage, nutritional supplement, animal feed for hangover relief and / or prevention or amelioration of after-hangover. BACKGROUND

[0002] In today's society, drinking is an important behavior in human life, people usually think that a small amount of alcohol can relieve anxiety and make people feel comfortable. However, long-term or excessive drinking can cause great harm to the human body. Many people will have after-hangover due to frequent drinking and over-drinking, and affect the normal life of the next day, and even many people will damage their health due to long-term bad drinking habits.

[0003] Alcohol hangover (hereinafter also referred to as "hangover") refers to various unpleasant physiological and psychological effects after drinking ethanol such as found in wine, beer, distilled spirits. Hangover symptoms usually appear a few hours after the intoxicating effects of alcohol begin to subside, for example, after waking up from sleep after heavy drinking. Symptoms of hangover can include headache, diarrhea, anorexia, nausea, vomiting, thirst, dry mouth, dizziness, fatigue, muscle cramps, decreased cognitive ability, poor visual-spatial coordination, pain, hallucinations, chills, tremors and sweating, cold sweats. Objective symptoms of hangover also include cognitive fog, decreased motor ability, hematological changes, and hormonal changes. The causes of hangover are known to be dehydration, toxicity of alcohol and alcohol metabolites (acetaldehyde, formaldehyde, acetone, etc.), and deficiency of nutrients (deficiency of blood sugar, vitamins, and minerals) caused by absorption disorders.

[0004] Wine is mainly metabolized and detoxified by the liver, and after entering the human body, it will increase the burden of the liver, affect the normal function of the liver, and cause liver damage; in addition, alcohol has a strong stimulating effect on the heart, brain, and blood vessels, and has an adverse effect on the nervous system of the human body, so long-term or excessive drinking can greatly increase the probability of cardiovascular and cerebrovascular diseases. After drinking, the emotional state of a person will also change, including many negative emotions, including the production of depression and depression after drinking, and the mechanism of its occurrence is not clear.

[0005] In view of the social background of drinking culture, the demand for hangover relief and alleviation products is increasing. Ergothioneine (EGT) is a safe natural compound with excellent anti-inflammatory and antioxidant properties. It is essential to study the relationship between ergothioneine (EGT) and compositions containing it and hangover relief, prevention or amelioration of after-hangover, or treatment, alleviation or amelioration of symptoms associated with hangover. SUMMARY

[0006] To achieve the above object, in one aspect, the present application provides a method for alcoholism relief and / or prevention or improvement of hangover, the method comprising administering to a mammal a composition comprising an effective amount of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof. In some embodiments, the composition can further comprise a pharmaceutically acceptable carrier.

[0007] In some embodiments, the alcoholism relief and / or prevention or improvement of hangover comprises increasing the tolerance of a subject to alcohol, reducing the alcohol intoxication effect in a subject who has consumed alcohol, sobering up a subject who has consumed alcohol, promoting the degradation of alcohol and acetaldehyde in a subject, activating alcohol metabolism in liver tissue of a subject, improving or restoring alcohol-induced liver damage, improving alcohol-induced movement disorder, preventing, ameliorating or alleviating adverse effects from alcohol hangover or symptoms associated with hangover.

[0008] In some embodiments, the adverse effects from alcohol hangover or symptoms associated with hangover are selected from one or more of the following: dizziness, headache, dehydration, hyperemia, stomach pain, anorexia, nausea, vomiting, diarrhea, tremor, sweating, fatigue, pain, muscle spasm, cognitive decline, poor visual-spatial coordination, hallucination, negative emotions or depression, acute alcohol-induced liver damage, cognitive fog.

[0009] In some embodiments, the alcoholism relief and / or prevention or improvement of hangover is achieved by increasing the activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reducing the oxidative stress on the liver from metabolizing alcohol.

[0010] In some embodiments, the composition further comprises an effective amount of para- xanthine or 1-methylxanthine. In some embodiments, the para-xanthine is natural or synthetic.

[0011] In some embodiments, the weight ratio of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof to para-xanthine or 1-methylxanthine is 1:50 to 20:1. In some embodiments, the weight ratio of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof to para-xanthine or 1-methylxanthine is 1:80 to 50:1, 1:60 to 30:1, 1:45 to 18:1, 1:40 to 15:1, 1:35 to 12:1, 1:30 to 10:1, 1:25 to 8:1, 1:20 to 6:1, 1:16 to 5:1, 1:10 to 3:1, 1:5 to 2:1, 1:1.

[0012] In some embodiments, the paraxanthine or 1-methylxanthine is formulated to be administered in an amount of 2-800 mg per day. In some embodiments, the paraxanthine or 1-methylxanthine can be formulated to be administered in an amount of 5-800 mg, 10-700 mg, 15-600 mg, 20-550 mg, 25-500 mg, 30-400 mg, 20-400 mg per day.

[0013] In some embodiments, the composition is administered before, during, or after drinking. In some embodiments, the composition can be used as a mood enhancer or relaxant for a subject experiencing a hangover.

[0014] In some embodiments, the composition is in a solid formulation or a liquid formulation. In some embodiments, the composition is in a solid oral dosage form.

[0015] In some embodiments, the composition is formulated in the form of a suppository, tablet, pill, granule, powder, film, injection, capsule, aerosol, spirit, tincture, tonic, solution, liquid suspension, or syrup.

[0016] In some embodiments, the composition is prepared as a food, beverage, nutritional supplement, animal feed.

[0017] In some embodiments, the composition is administered orally, intravenously, intramuscularly, intraperitoneally, or sublingually.

[0018] In some embodiments, the ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof is formulated to be administered in an amount of 1-1500 mg per day. In some embodiments, the ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof can be formulated to be administered in an amount of 1-1000 mg, 2-500 mg, 3-200 mg, 4-100 mg, 5-50 mg, 10-30 mg per day.

[0019] In another aspect, the present application provides a composition comprising ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof for use in alcohol abstinence and / or prevention or amelioration of a hangover. In some embodiments, the composition can further comprise a pharmaceutically acceptable carrier.

[0020] In some embodiments, alcohol abstinence and / or prevention or amelioration of a hangover comprises increasing the tolerance of a subject to alcohol, reducing the alcohol intoxication effect in a subject who has consumed alcohol, sobering up a subject who has consumed alcohol, promoting the degradation of alcohol and acetaldehyde in a subject, activating alcohol metabolism in liver tissue of a subject, improving or restoring alcohol-induced liver damage, improving alcohol-induced movement disorders, preventing, ameliorating, or alleviating adverse effects or symptoms associated with a hangover or acute alcohol poisoning.

[0021] In some embodiments, the adverse effects from alcohol hangover or acute alcohol poisoning or symptoms associated with hangover are selected from one or more of the following: dizziness, headache, dehydration, hyperemia, stomach pain, anorexia, nausea, vomiting, diarrhea, tremors, sweating, fatigue, pain, muscle cramps, cognitive decline, poor visual-spatial coordination, hallucinations, negative emotions or depression, acute alcoholic liver injury, cognitive fog.

[0022] In some embodiments, the alcohol hangover and / or prevention or amelioration of hangover is achieved by increasing the activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reducing oxidative stress on the liver from metabolizing alcohol.

[0023] In some embodiments, the composition further comprises an effective amount of para- xanthine or 1-methylxanthine. In some embodiments, the para-xanthine is natural or synthetic.

[0024] In some embodiments, the weight ratio of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof to para-xanthine or 1-methylxanthine is 1:50 to 20:1. In some embodiments, the weight ratio of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof to para-xanthine or 1-methylxanthine is 1:80 to 50:1, 1:60 to 30:1, 1:45 to 18:1, 1:40 to 15:1, 1:35 to 12:1, 1:30 to 10:1, 1:25 to 8:1, 1:20 to 6:1, 1:16 to 5:1, 1:10 to 3:1, 1:5 to 2:1, 1:1.

[0025] In some embodiments, the para-xanthine or 1-methylxanthine is formulated to be administered in an amount of 2-800 mg per day. In some embodiments, the para-xanthine or 1-methylxanthine can be formulated to be administered in an amount of 5-800 mg, 10-700 mg, 15-600 mg, 20-550 mg, 25-500 mg, 30-400 mg, 20-400 mg per day.

[0026] In some embodiments, the composition is administered before, during, or after alcohol consumption. In some embodiments, the composition can be used as a mood enhancer or relaxant for a subject experiencing a hangover.

[0027] In some embodiments, the composition is in a solid formulation or a liquid formulation. In some embodiments, the composition is in a solid oral dosage form.

[0028] In some embodiments, the composition is formulated in the form of a suppository, tablet, pill, granule, powder, film, injection, capsule, aerosol, spirit, tincture, tonic, solution, liquid suspension, or syrup.

[0029] In some embodiments, the composition is prepared as a food, beverage, nutritional supplement, animal feed.

[0030] In some embodiments, the ergothioneine or pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof is formulated to be administered in an amount of 1-1500 mg per day. In some embodiments, the ergothioneine or pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof can be formulated to be administered in an amount of 1-1000 mg, 2-500 mg, 3-200 mg, 4-100 mg, 5-50 mg, 10-30 mg per day.

[0031] In another aspect, the present application provides use of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof in the preparation of a composition for alcohol abstinence and / or prevention or amelioration of hangover.

[0032] In some embodiments, alcohol abstinence and / or prevention or amelioration of hangover comprises increasing tolerance to alcohol in a subject, reducing alcohol intoxication in a subject who has consumed alcohol, sobering up a subject who has consumed alcohol, promoting alcohol and acetaldehyde degradation in a subject, activating alcohol metabolism in liver tissue of a subject, improving or restoring alcohol-induced liver damage, improving alcohol-induced motor impairment, preventing, ameliorating, or alleviating adverse effects from alcohol hangover or symptoms associated with hangover.

[0033] In some embodiments, the adverse effects from alcohol hangover or symptoms associated with hangover are selected from one or more of the following: dizziness, headache, dehydration, hyperemia, stomach pain, anorexia, nausea, vomiting, diarrhea, tremors, sweating, fatigue, pain, muscle cramps, cognitive decline, poor visual-spatial coordination, hallucinations, negative emotions or depression, acute alcohol-induced liver damage, cognitive fog.

[0034] In some embodiments, alcohol abstinence and / or prevention or amelioration of hangover is achieved by increasing activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reducing oxidative stress on the liver from metabolizing alcohol.

[0035] In some embodiments, the composition further comprises an effective amount of para- xanthine or 1-methyl xanthine. In some embodiments, the para-xanthine is natural or synthetic.

[0036] In some embodiments, the ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof is formulated in a weight ratio of 1:50 to 20:1 with the paraxanthine or 1-methylxanthine. In some embodiments, the ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof is formulated in a weight ratio of 1:80 to 50:1, 1:60 to 30:1, 1:45 to 18:1, 1:40 to 15:1, 1:35 to 12:1, 1:30 to 10:1, 1:25 to 8:1, 1:20 to 6:1, 1:16 to 5:1, 1:10 to 3:1, 1:5 to 2:1, 1:1 with the paraxanthine or 1-methylxanthine.

[0037] In some embodiments, the paraxanthine or 1-methylxanthine is formulated to be administered in an amount of 2-800 mg per day. In some embodiments, the paraxanthine or 1-methylxanthine can be formulated to be administered in an amount of 5-800 mg, 10-700 mg, 15-600 mg, 20-550 mg, 25-500 mg, 30-400 mg, 20-400 mg per day.

[0038] In some embodiments, the composition is administered prior to, during, or after alcohol consumption. In some embodiments, the composition can be used as a mood enhancer or relaxant for a subject experiencing a hangover.

[0039] In some embodiments, the composition is in a solid formulation or a liquid formulation. In some embodiments, the composition is in a solid oral dosage form.

[0040] In some embodiments, the composition is formulated in the form of a suppository, tablet, pill, granule, powder, film, injection, capsule, aerosol, spirit, tincture, tonic, solution, liquid suspension, or syrup.

[0041] In some embodiments, the composition is prepared as a food, beverage, nutritional supplement, animal feed.

[0042] In some embodiments, the ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof is formulated to be administered in an amount of 1-1500 mg per day. In some embodiments, the ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof can be formulated to be administered in an amount of 1-1000 mg, 2-500 mg, 3-200 mg, 4-100 mg, 5-50 mg, 10-30 mg per day.

[0043] The summary is provided to introduce a selection of concepts that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter. Attached Figure Description

[0044] Figure 1 shows the number of times mice moved 2 hours after drinking alcohol in each group.

[0045] Figure 2 shows the distance traveled by mice in each group 2 hours after drinking alcohol.

[0046] Figure 3 shows the movement time of mice in each group 2 hours after drinking alcohol.

[0047] Figure 4 shows the average movement speed of mice in each group 2 hours after drinking alcohol.

[0048] Figure 5 shows the number of pauses in each group of mice 2 hours after drinking alcohol.

[0049] Figure 6 shows the time 2 hours after alcohol consumption in each group of mice.

[0050] Figure 7 shows the plasma ethanol concentration of mice in each group 2 hours after drinking alcohol.

[0051] Figure 8 shows the plasma acetaldehyde concentration in mice 2 hours after drinking alcohol.

[0052] Figure 9 shows the plasma ALT concentration of mice in each group 2 hours after drinking alcohol.

[0053] Figure 10 shows the plasma AST concentration of mice in each group 2 hours after drinking alcohol.

[0054] Figure 11 shows the plasma ADH enzyme activity of mice in each group 2 hours after drinking alcohol.

[0055] Figure 12 shows the plasma ALDH enzyme activity of mice in each group 2 hours after drinking alcohol.

[0056] Figure 13 shows the MDA levels of mice in each group.

[0057] Figure 14 shows the GSH levels of mice in each group.

[0058] Figure 15 shows the SOD levels of mice in each group.

[0059] Figure 16 shows the TNF-α levels in each group of mice.

[0060] Figure 17 shows the IL-6 levels in each group of mice. Detailed Implementation

[0061] The present invention will now be further described with reference to preferred embodiments thereof. While the invention will be described in conjunction with preferred embodiments, it should be understood that they are not intended to limit the invention to these embodiments. Rather, the invention is intended to cover alternatives, modifications, and equivalents that may be included within the spirit and scope of the invention as defined in the claims.

[0062] As used herein, the term “or” is intended to mean “and” and “or.” In other words, the term “or” shall be construed in the same manner as the term “and / or”.

[0063] As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0064] As used herein, the terms “comprising” or “including,” or variations thereof, means that the terms are used in their non-limiting sense and shall be construed to mean “including but not limited to,” unless otherwise indicated.

[0065] As used herein, the terms “mammal” or “subject” are used interchangeably to refer to any animal to which the methods and compositions of the present disclosure can be applied or administered. The animal can be suffering from an ailment or other disease, but the animal need not be ill in order to benefit from the methods and compositions of the present disclosure. Thus, any animal can utilize the disclosed compositions or be the recipient of the disclosed methods. Although the animal subject is preferably a human, the methods and compositions of the present disclosure are equally applicable to veterinary medicine, for example, for treating domesticated species such as canines, felines, murines, and various other pets; farm animals, such as cattle, horses, sheep, goats, swine, and the like; and wild animals, such as non-human primates in the wild or in zoos, and the like.

[0066] As used herein, the term “administering” refers to the process of delivering the disclosed compositions or active ingredients to a subject. The compositions of the present disclosure are preferably administered by oral, intravenous, intramuscular, intraperitoneal, or sublingual administration, and the like, but can also be administered by other conventional routes to exert the desired effect. The compositions of the present disclosure can be administered prior to, during, and / or after alcohol consumption.

[0067] As used herein, the term “effective amount” refers to the amount necessary to achieve an effect as taught herein. Effective amounts herein include, but are not limited to, amounts necessary to sober up and / or prevent or ameliorate a hangover, and / or increase tolerance to alcohol, sober up a subject who has consumed alcohol, promote the degradation of alcohol and acetaldehyde in the body, activate alcohol metabolism in liver tissue, improve or restore liver function, improve alcohol-induced motor impairment, prevent or alleviate adverse effects from a hangover or acute alcohol poisoning, prevent or alleviate damage or symptoms from chronic alcohol poisoning, and / or increase the activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reduce oxidative stress on the liver from metabolizing alcohol. In accordance with the present disclosure, a suitable single dose size is a dose that is capable of achieving the above effects when administered one or more times over a suitable period of time.

[0068] As used herein, the term "pharmaceutically acceptable" means pharmacologically, physiologically, nutritionally, dietetically acceptable, and refers to those which are within the scope of sound medical judgment of those compositions or agents, materials or compositions and / or their dosage forms, which are suitable for use in contact with the tissues of human beings and animals, compatible with the other ingredients of the composition, not unreasonably toxic, irritating, allergenic or otherwise inappropriate, and commensurate in risk with the potential benefit.

[0069] As used herein, the term "alcohol hangover" or "hangover" refers to an unpleasant physical condition exhibited by the ingestion of alcoholic beverages, which can be accompanied by symptoms such as nausea, vomiting, headache, dizziness, tremors, fatigue, muscle cramps, cognitive impairment, poor visual-spatial coordination, pain, hallucinations, shakiness, and / or sweating. It is generally understood that alcohol sickness is primarily caused by symptoms resulting from acetaldehyde produced during the metabolism of ethanol after the ingestion of alcoholic beverages. For example, a hangover can refer to the above conditions occurring within 24 hours after the onset of the ingestion of alcoholic beverages.

[0070] In certain embodiments, the composition is administered to the subject prior to alcohol ingestion. In exemplary embodiments, the subject has a history of experiencing a hangover after alcohol ingestion. In other embodiments, the composition is administered to the subject during alcohol ingestion. In further embodiments, the composition is administered to the subject at the onset of hangover symptoms. Hangover symptoms include those described above in connection with a hangover.

[0071] According to certain embodiments, the composition is administered in conjunction with one or more treatments or therapies. In exemplary embodiments, the one or more treatments or therapies are selected from the group consisting of: fluids, electrolytes, caffeine, and / or non-opioid analgesics.

[0072] In some embodiments, the ergothioneine or pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof of the present application and / or compositions comprising the same can be prepared with a dietetically or pharmaceutically acceptable carrier as a composition. Such carriers include those normally used in health food and dietary supplement and pharmaceutical preparations, such as sugars, starches, cellulose and its derivatives, powdered tragacanth, malt, gelatin, talc, oils, diols, polyols, esters, agar, alginic acid, pyrogen-free water, isotonic saline, and the like.

[0073] In some embodiments, the ergothioneine or pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof of the present application and / or compositions comprising the same can be administered with other supplements, such as vitamins, minerals, nootropics, and other supplements known in the art.

[0074] The methods of the present application include administration of at least 1 mg, typically 1-1500 mg, 1-2300 mg, preferably 1-1000 mg, 2-500 mg, 3-200 mg, 4-100 mg, 5-50 mg, 10-30 mg of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof or a composition comprising the same per day, depending on the particular formulation and form. The amount to be administered can also vary depending on factors such as the sensitivity, age, sex and weight of the subject, idiosyncratic reactions, etc. One or more doses can be administered one or more times per day or at suitable frequencies over any time period. For example, an effective dose can be administered daily for one day, several days, many days, or indefinitely.

[0075] The following examples are illustrative of selected embodiments of the application, and are not meant to limit the scope of the application. Example 1

[0076] Take 1 part (by weight) of ergothioneine, mix with 1 part (by weight) of para- xanthine in a three-dimensional mixer, and mix uniformly to obtain the composition described in Example 1. Examples 2-10

[0077] Examples 2-10 are prepared in the same way as Example 1. The weight parts of para-xanthine and ergothioneine are shown in the following table: Example 11

[0078] This example studies the effect of ergothioneine and compositions comprising the same on hangover after drinking by using a mouse acute alcohol withdrawal model. 1. Experimental animals

[0079] Forty 6-8 week old C57BL / 6J wild type mice, weighing 20±2 g, were raised in a constant temperature and humidity animal room, with a temperature of 22℃±2℃ and a humidity of 50±5%, under a 12 hour light-dark cycle. The animals were acclimated for one week before the experiment, during which water and feed were freely taken. One week later, they were randomly divided into a control group, a model group, an experimental group 1 (ergothioneine, 35 mg / kg), an experimental group 2 (Example 7, 35 mg / kg), and an experimental group 3 (Example 9, 35 mg / kg), with 8 animals in each group.

[0080] The animals were ready for the experiment after pre-rearing. The control group was administered distilled water (0.6 g / kg), and the model group and the experimental groups were administered absolute alcohol (0.6 g / kg) and the vehicle or the corresponding supplement, respectively, by gavage.

[0081] The vehicle or the supplement was administered to each experimental group 30 minutes before the administration of alcohol, and the observation experiment was performed 2 hours after the administration of alcohol.

[0082] The spontaneous exploration ability and behavior of mice in a new environment were observed using the Open-field method. A single mouse was observed in a separate opaque container (40 cm*70 cm*40 cm), and the real-time activity of the mouse was recorded by video. The behavior was analyzed by ANY-maze software, including the number of movements, movement distance, movement time, average movement speed, number of stops, and stop time.

[0083] After the observation experiment was completed, the animals were bled (about 0.5 mL), and the collected blood samples were stored in EP tubes containing NaF to prevent alcohol degradation. If necessary, the samples were stored at -80°C. The blood samples were centrifuged at 4°C and 3000 rpm for 10 min, and the supernatant was collected for the detection of ethanol, acetaldehyde concentration, ALT, and AST. After blood collection, CO2 euthanasia was performed, and the liver was dissected. Equal amounts of liver tissue were homogenized with PBS at a mass ratio of 1:9. The specimen was lysed, centrifuged at 4°C and 10000 rpm for 10 min, and the supernatant was detected for ADH and ALDH activity.

[0084] Graphpad 10.0 software was used for data analysis, and the results were expressed as standard deviation (x ± s). Two-way ANOVA test was used for significance analysis.

[0085] In the embodiments of the present application, ergothioneine administered to mice can improve alcohol-induced movement disorders, increase alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity, promote the degradation of alcohol and acetaldehyde in the body, and have a certain positive effect on relieving alcohol hangover.

[0086] Figure 1 is the number of movements of mice in each group 2 hours after drinking. As shown in Figure 1, the number of movements of mice in the model group 2 hours after drinking decreased by 36.4% compared with the control group. The number of movements of each drinking mouse in experimental group 1, experimental group 2, and experimental group 3, which were administered with ergothioneine or a combination of ergothioneine and para-xanthine, increased by 9.1%, decreased by only 18.2%, and increased by 22.7%, respectively, compared with the control group. The administration of ergothioneine or a combination of ergothioneine and para-xanthine can improve the number of movements of mice after drinking.

[0087] Figure 2 is the movement distance of mice in each group 2 hours after drinking. As shown in Figure 2, the movement distance of mice in the model group 2 hours after drinking decreased by 44.6% compared with the control group. The movement distance of each drinking mouse in experimental group 1, experimental group 2, and experimental group 3, which were administered with ergothioneine or a combination of ergothioneine and para-xanthine, increased by only 1.4%, 3.4%, and 6.9%, respectively, compared with the control group. The administration of ergothioneine or a combination of ergothioneine and para-xanthine can improve the movement distance of mice after drinking.

[0088] Figure 3 is the moving time of each group of mice 2 hours after drinking. As shown in Figure 3, the moving time of the model group mice 2 hours after drinking decreased by 27.6% compared with the control group; while the moving time of each drinking mouse of experimental group 1, experimental group 2 and experimental group 3, which were administered ergothioneine or ergothioneine and para-xanthine composition, increased, and decreased by 6.9%, 3.5% and 12.1% respectively compared with the control group. Ergothioneine or ergothioneine and para-xanthine composition can improve the moving time of mice after drinking.

[0089] Figure 4 is the moving average speed of each group of mice 2 hours after drinking. As shown in Figure 4, the moving average speed of the model group mice 2 hours after drinking decreased by 23.5% compared with the control group; while the moving average speed of each drinking mouse of experimental group 1, experimental group 2 and experimental group 3, which were administered ergothioneine or ergothioneine and para-xanthine composition, increased by 5.9%, the same as the control group and 5.9% respectively. Ergothioneine or ergothioneine and para-xanthine composition can improve the moving average speed of mice after drinking.

[0090] Figure 5 is the number of stops of each group of mice 2 hours after drinking. As shown in Figure 5, the number of stops of the model group mice 2 hours after drinking increased by 66.6% compared with the control group; while the number of stops of each drinking mouse of experimental group 1, experimental group 2 and experimental group 3, which were administered ergothioneine or ergothioneine and para-xanthine composition, decreased by 16.7% and 16.7% respectively and the same as the control group. Ergothioneine or ergothioneine and para-xanthine composition can improve the number of stops of mice after drinking.

[0091] Figure 6 is the stop time of each group of mice 2 hours after drinking. As shown in Figure 6, the stop time of the model group mice 2 hours after drinking increased by 800% compared with the control group; while the stop time of each drinking mouse of experimental group 1, experimental group 2 and experimental group 3, which were administered ergothioneine or ergothioneine and para-xanthine composition, decreased by 200%, 100% and 350% respectively compared with the control group. Ergothioneine or ergothioneine and para-xanthine composition can improve the stop time of mice after drinking.

[0092] Figure 7 is the plasma ethanol concentration of each group of mice 2 hours after drinking. As shown in Figure 7, the ethanol concentration in the plasma of the model group mice 2 hours after drinking reached 0.46%; while the plasma ethanol concentration of each drinking mouse of experimental group 1, experimental group 2 and experimental group 3, which were administered ergothioneine or ergothioneine and para-xanthine composition, decreased by 10.9%, 15.2% and 17.4% respectively compared with the model group. Ergothioneine or ergothioneine and para-xanthine composition can improve the plasma ethanol concentration of mice after drinking and accelerate the metabolism of ethanol.

[0093] Figure 8 is the plasma acetaldehyde concentration of each group of mice 2h after alcohol consumption. As shown in Figure 8, the plasma acetaldehyde concentration of the model group mice 2h after alcohol consumption reached 116 nmol / L; while the plasma acetaldehyde concentration of each of the alcohol-consuming mice of experimental group 1, experimental group 2, and experimental group 3, which were administered ergothioneine or ergothioneine and a para-xanthine composition, decreased, and decreased by 41.2%, 47.4%, and 44.8% respectively, compared to the model group. Ergothioneine or ergothioneine and a para-xanthine composition can improve the plasma acetaldehyde concentration of mice after alcohol consumption.

[0094] Figure 9 is the plasma ALT concentration of each group of mice 2h after alcohol consumption. As shown in Figure 9, the plasma ALT concentration of the model group mice 2h after alcohol consumption increased to 154 U / L; while the plasma ALT concentration of each of the alcohol-consuming mice of experimental group 1, experimental group 2, and experimental group 3, which were administered ergothioneine or ergothioneine and a para-xanthine composition, decreased, and decreased by 43.5%, 35.7%, and 56.5% respectively, compared to the model group. Ergothioneine or ergothioneine and a para-xanthine composition can improve the plasma ALT concentration of mice after alcohol consumption.

[0095] Figure 10 is the plasma AST concentration of each group of mice 2h after alcohol consumption. As shown in Figure 10, the plasma AST concentration of the model group mice 2h after alcohol consumption increased to 365 U / L; while the plasma AST concentration of each of the alcohol-consuming mice of experimental group 1, experimental group 2, and experimental group 3, which were administered ergothioneine or ergothioneine and a para-xanthine composition, decreased, and decreased by 49.7%, 57.3%, and 65.2% respectively, compared to the model group. Ergothioneine or ergothioneine and a para-xanthine composition can improve the plasma AST concentration of mice after alcohol consumption.

[0096] Figure 11 is the plasma ADH enzyme activity of each group of mice 2h after alcohol consumption. As shown in Figure 11, the plasma ADH of the model group mice 2h after alcohol consumption increased by 325% compared to the control group; while the ADH of each of the alcohol-consuming mice of experimental group 1, experimental group 2, and experimental group 3, which were administered ergothioneine or ergothioneine and a para-xanthine composition, further increased, and increased by 400%, 413%, and 450% respectively, compared to the control group. Ergothioneine or ergothioneine and a para-xanthine composition can further activate the ADH of mice after alcohol consumption, helping to metabolize ethanol.

[0097] Figure 12 is the plasma ALDH enzyme activity of each group of mice 2h after drinking. As can be seen from Figure 12, the ALDH in the plasma of the model group of mice 2h after drinking increased by 128% compared with the control group; while the ALDH of each of the experimental group 1, experimental group 2, and experimental group 3 of mice administered ergothioneine or ergothioneine and paraxanthine composition after drinking further increased, increased by 171%, 257%, and 214% respectively compared with the control group. The administration of ergothioneine or ergothioneine and paraxanthine composition can further activate the ALDH of mice after drinking, helping to metabolize acetaldehyde.

[0098] In this embodiment, the administration of ergothioneine and ergothioneine and paraxanthine composition to mice can improve the behavior of mice 2h after drinking, accelerate the metabolism of ethanol and acetaldehyde in the blood, reduce the concentration of ALT and AST in the blood, and increase the enzyme activity of ADH and ALDH in the liver, and has an improvement effect on alcohol metabolism and hangover behavior after drinking.

[0099] This embodiment studies the effect of ergothioneine and compositions containing the same on the oxidative stress of the liver caused by drinking through a chronic drinking mouse model. 1. Experimental animals

[0100] Forty 6-8 week old C57BL / 6J wild type mice, weighing 20±2g, were raised in a constant temperature and humidity animal room, with a temperature of 22℃±2℃ and a humidity of 50±5%, under a 12 hour light-dark cycle. One week before the experiment, the mice were adapted to the environment, during which they were allowed to freely take water and feed. One week later, the mice were randomly divided into a control group, a model group, and experimental groups 1 (ergothioneine, 3.5mg / kg), 2 (Example 3, 3.5mg / kg), and 3 (Example 8, 3.5mg / kg), with 8 mice in each group.

[0101] After the pre-cultured animals were completed, the experiment was performed. After the experiment began, the control group was raised under the same conditions, while the model group and the experimental groups were changed to freely drink a 5% alcohol water solution for 7 days. The model group and the experimental groups were additionally administered the vehicle or the supplement at a fixed time every day.

[0102] After the administration of ergothioneine for 2h on the 7th day, the mice were euthanized with CO2, and the liver and kidney were removed and weighed to calculate the organ coefficients. The same mass of liver tissue from the same part was used for index detection, and PBS was used for homogenization at a mass ratio of 1:9. If necessary, the sample specimens were stored using liquid nitrogen. After the cells were lysed, the supernatant was detected for malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), TNF-α, and IL-6 after centrifugation at 3000g for 15min at 4℃.

[0103] Data were analyzed using Graphpad 10.0 software, and the results were expressed as standard deviation (x ± s) and analyzed for significance using two-way ANOVA test.

[0104] Figure 13 is the MDA level of mice in each group. As can be seen from Figure 13, the MDA level in the liver of the model group mice increased significantly during continuous alcohol consumption, which was 13 times higher than that of the control group. The MDA level in the liver of each alcohol-consuming mouse in experimental group 1, experimental group 2, and experimental group 3, which were administered ergothioneine or ergothioneine and paraxanthine composition, was controlled to a certain extent, which was only 11.0 times, 10.0 times, and 8.3 times higher than that of the control group, respectively. The administration of ergothioneine or ergothioneine and paraxanthine composition can reduce the MDA level in the liver of mice after alcohol consumption, and reduce the oxidative stress of the liver caused by alcohol consumption.

[0105] Figure 14 is the GSH level of mice in each group. As can be seen from Figure 14, the GSH level in the liver of the model group mice decreased significantly during continuous alcohol consumption, which was 20.6% lower than that of the control group. The GSH level in the liver of each alcohol-consuming mouse in experimental group 1, experimental group 2, and experimental group 3, which were administered ergothioneine or ergothioneine and paraxanthine composition, increased to a certain extent, which was 2.9%, even 20.1%, and 23.5% higher than that of the control group, respectively. The administration of ergothioneine or ergothioneine and paraxanthine composition can increase the GSH level in the liver of mice after alcohol consumption, and improve the antioxidant capacity of the liver.

[0106] Figure 15 is the SOD level of mice in each group. As can be seen from Figure 15, the SOD level in the liver of the model group mice decreased significantly during continuous alcohol consumption, which was 47.1% lower than that of the control group. The SOD level in the liver of each alcohol-consuming mouse in experimental group 1, experimental group 2, and experimental group 3, which were administered ergothioneine or ergothioneine and paraxanthine composition, increased to a certain extent, which was only 18.8%, 10.3%, and 5.4% lower than that of the control group, respectively. The administration of ergothioneine or ergothioneine and paraxanthine composition can increase the SOD level in the liver of mice after alcohol consumption, and improve the antioxidant capacity of the liver.

[0107] Figure 16 is the TNF-a level of each group of mice. As can be seen from Figure 16, the TNF-a level in the liver of the model group mice increased significantly during continuous alcohol consumption, which was increased by 107.0% compared with the control group; while the liver TNF-a level of each alcohol-consuming mouse of the experimental group 1, the experimental group 2, and the experimental group 3 administered ergothioneine or the combination of ergothioneine and paraxanthine composition was inhibited to a certain extent, which was only increased by 18.8%, decreased by 16.3%, and increased by 9.3% compared with the control group, respectively. The administration of ergothioneine or the combination of ergothioneine and paraxanthine composition can inhibit the TNF-a level in the liver of the mice after alcohol consumption, indicating that the liver inflammation level is lighter. The combination of ergothioneine and paraxanthine has a better combination effect.

[0108] Figure 17 is the IL-6 level of each group of mice. As can be seen from Figure 17, the IL-6 level in the liver of the model group mice increased significantly during continuous alcohol consumption, which was increased by 53.3% compared with the control group; while the liver IL-6 level of each alcohol-consuming mouse of the experimental group 1, the experimental group 2, and the experimental group 3 administered ergothioneine or the combination of ergothioneine and paraxanthine composition was inhibited to a certain extent, which was only increased by 22.8%, 6.5%, and 13.0% compared with the control group, respectively. The administration of ergothioneine or the combination of ergothioneine and paraxanthine composition can inhibit the IL-6 level in the liver of the mice after alcohol consumption, indicating that the liver inflammation level is lighter. The combination of ergothioneine and paraxanthine has a better combination effect.

[0109] In this embodiment, the administration of ergothioneine or the combination of ergothioneine and paraxanthine to the alcohol-consuming mice can reduce the oxidative stress of the liver due to the metabolism of alcohol, improve the antioxidant capacity of the liver, reduce the increased inflammation level of the liver due to alcohol damage, and improve liver function.

[0110] The present inventors found that the composition comprising EGT of the present application and the method of the present application have a positive regulatory effect on alcoholism and / or prevention or improvement of hangover, can increase the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), promote the degradation of alcohol and acetaldehyde in the body, reduce the oxidative stress and inflammation level of the liver due to the metabolism of alcohol, and reduce the harm of alcohol consumption.

[0111] Although specific embodiments and examples of the present application have been described herein, those skilled in the art will understand that any modifications and variations can be made without departing from the principles of the present application. The above examples and descriptions are not intended to limit the scope of the present application. Any combination of the embodiments of the present application, as well as any obvious extension or analogue thereof, is within the scope of the present application. In addition, the present application encompasses any arrangement intended to achieve the same purpose, as well as all such variations and modifications falling within the scope of the appended claims.

Claims

1. A method for alleviating alcohol hangover and / or preventing or ameliorating alcohol intoxication, characterized by, The method comprises administering to a subject in need thereof a composition comprising an effective amount of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof.

2. The method of claim 1, wherein, The alcoholism and / or prevention or improvement of hangover comprises increasing the subject's tolerance to alcohol, reducing the alcohol intoxication effect in a subject who has consumed alcohol, sobering up a subject who has consumed alcohol, promoting the degradation of alcohol and acetaldehyde in a subject, activating alcohol metabolism in a subject's liver tissue, improving or restoring alcoholic liver damage, improving alcohol-induced movement disorders, preventing, improving or alleviating adverse reactions from alcohol hangover or symptoms associated with hangover.

3. The method of claim 2, wherein, The adverse reactions from alcohol hangover or symptoms associated with hangover are selected from one or more of the following: dizziness, headache, dehydration, hyperemia, stomach pain, anorexia, nausea, vomiting, diarrhea, tremor, sweating, fatigue, pain, muscle spasm, cognitive decline, poor visual-spatial coordination, hallucinations, negative emotions or depression, acute alcoholic liver damage, cognitive fog.

4. The method according to any one of claims 1 to 3, characterized in that, The alcoholism and / or prevention or improvement of hangover is achieved by increasing the activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reducing the oxidative stress on the liver from metabolizing alcohol.

5. The method according to any one of claims 1 to 4, characterized in that, The composition further comprises an effective amount of para- xanthine or 1-methyl xanthine.

6. The method of claim 5, wherein, The weight ratio of the ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof to the para- xanthine or 1-methyl xanthine is 1:50 to 20:

1.

7. The method according to claim 5 or 6, characterized in that, The para- xanthine or 1-methyl xanthine is formulated to be administered in an amount of 2-800 mg per day.

8. The method according to any one of claims 1 to 7, characterized in that, The composition is administered before, during or after alcohol consumption.

9. The method according to any one of claims 1 to 8, characterized in that, The composition is in a solid or liquid formulation.

10. The method according to any one of claims 1 to 9, characterized in that, The composition is formulated in the form of a suppository, tablet, pill, granule, powder, film, injection, capsule, aerosol, spirit, tincture, tonic, solution, liquid suspension or syrup.

11. The method according to any one of claims 1 to 10, characterized in that, The composition is prepared as a food, beverage, nutritional supplement, animal feed.

12. The method according to any one of claims 1 to 11, characterized in that, The composition is administered orally, intravenously, intramuscularly, intraperitoneally or sublingually.

13. The method according to any one of claims 1 to 12, characterized in that, The ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof is formulated to be administered in an amount of 1-1500 mg per day.

14. A composition comprising ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof, characterized in that, The composition is used for alcoholism and / or prevention or improvement of hangover.

15. The composition of claim 14, wherein, The alcoholism and / or prevention or improvement of hangover comprises increasing the subject's tolerance to alcohol, reducing the alcohol intoxication effect in a subject who has consumed alcohol, sobering up a subject who has consumed alcohol, promoting the degradation of alcohol and acetaldehyde in a subject, activating alcohol metabolism in a subject's liver tissue, improving or restoring alcoholic liver damage, improving alcohol-induced movement disorders, preventing, improving or alleviating adverse reactions from alcohol hangover or symptoms associated with hangover.

16. The composition of claim 15, wherein, The adverse effects from alcohol hangover or hangover-related symptoms associated with the hangover are selected from one or more of the following: dizziness, headache, dehydration, hyperemia, stomach pain, anorexia, nausea, vomiting, diarrhea, tremors, sweating, fatigue, pain, muscle cramps, cognitive decline, poor visual-spatial coordination, hallucinations, negative emotions or depression, acute alcoholic liver injury, cognitive fog.

17. The composition according to any one of claims 14 to 16, characterized in that, The alcohol hangover prevention or improvement is achieved by increasing the activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reducing oxidative stress on the liver from metabolizing alcohol.

18. The composition according to any one of claims 14 to 17, characterized in that, The composition further comprises an effective amount of para- xanthine or 1-methyl xanthine.

19. The composition of claim 18, wherein, The ergothioneine or pharmaceutically acceptable salt, acid, ester, analog or derivative thereof and the para-xanthine or 1-methyl xanthine are in a weight ratio of 1:50 to 20:

1.

20. The composition of claim 18 or 19, wherein, The para-xanthine or 1-methyl xanthine is formulated to be administered in an amount of 2-800 mg per day.

21. The composition according to any one of claims 14 to 20, characterized in that, The composition is administered before, during or after alcohol consumption.

22. The composition of any one of claims 14 to 21, wherein, The composition is in a solid formulation or a liquid formulation.

23. The composition of any one of claims 14 to 22, wherein, The composition is formulated in the form of a suppository, tablet, pill, granule, powder, film, injection, capsule, aerosol, spirit, tincture, tonic, solution, liquid suspension or syrup.

24. The composition of any one of claims 14 to 23, wherein, The composition is prepared as a food, beverage, nutritional supplement, animal feed.

25. The composition of any one of claims 14 to 24, wherein, The ergothioneine or pharmaceutically acceptable salt, acid, ester, analog or derivative thereof is formulated to be administered in an amount of 1-1500 mg per day.

26. Use of ergothioneine or pharmaceutically acceptable salt, acid, ester, analog or derivative thereof in the preparation of a composition for alcohol hangover prevention or improvement.

27. Use according to claim 26, characterized in that, The alcohol hangover prevention or improvement includes increasing the tolerance of a subject to alcohol, reducing the alcohol intoxication effect on a subject who consumes alcohol, sobering up a subject who has consumed alcohol, promoting the degradation of alcohol and acetaldehyde in a subject, activating alcohol metabolism in liver tissue of a subject, improving or restoring alcoholic liver injury, improving alcohol-induced movement disorder, preventing, improving or alleviating adverse effects from alcohol hangover or hangover-related symptoms associated with the hangover.

28. Use according to claim 27, characterized in that, The adverse effects from alcohol hangover or hangover-related symptoms associated with the hangover are selected from one or more of the following: dizziness, headache, dehydration, hyperemia, stomach pain, anorexia, nausea, vomiting, diarrhea, tremors, sweating, fatigue, pain, muscle cramps, cognitive decline, poor visual-spatial coordination, hallucinations, negative emotions or depression, acute alcoholic liver injury, cognitive fog.

29. Use according to any one of claims 26 to 28, characterized in that, The alcohol hangover prevention or improvement is achieved by increasing the activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reducing oxidative stress on the liver from metabolizing alcohol.

30. The use according to any one of claims 26 to 29, characterized in that, The composition further comprises an effective amount of para- xanthine or 1-methyl xanthine.

31. Use according to claim 30, characterized in that, The ergothioneine or pharmaceutically acceptable salt, acid, ester, analog or derivative thereof and the para-xanthine or 1-methyl xanthine are in a weight ratio of 1:50 to 20:

1.

32. Use according to claim 30 or 31, characterized in that, The para-xanthine or 1-methyl xanthine is formulated to be administered in an amount of 2-800 mg per day.

33. The use according to any one of claims 26 to 32, characterized in that, The composition is administered before, during or after drinking.

34. The use according to any one of claims 26 to 33, characterized in that, The composition is in a solid preparation or a liquid preparation.

35. The use according to any one of claims 26 to 34, characterized in that, The composition is formulated in the form of a suppository, a tablet, a pill, a granule, a powder, a film, an injection, a capsule, an aerosol, a spirit, a tincture, a tonic, a solution, a liquid suspension or a syrup.

36. The use according to any one of claims 26 to 35, characterized in that, The composition is prepared as a food, a beverage, a nutritional supplement, an animal feed.

37. The use according to any one of claims 26 to 36, characterized in that, The ergothioneine or a pharmaceutically acceptable salt, acid, ester, analogue or derivative thereof is formulated to be administered in an amount of 1-1500 mg per day.

Images