Paraxanthine for dispelling effects of alcohol and / or preventing or ameliorating hangover

Abstract

The invention discloses application of paraxanthine in preparation of a composition for dispelling the effects of alcohol and / or preventing or improving hangover. The methods and compositions of the present invention can increase the tolerance of a subject to alcohol, alleviate the alcohol-induced drunkenness of a drunken subject, wake up the drunken subject, promote the degradation of alcohol and acetaldehyde in the body of the subject, activate the alcohol metabolism in the liver tissue of the subject, improve or recover alcoholic liver injury, improve alcohol-induced dyskinesia, and improve alcohol-induced dyskinesia. And adverse reactions or symptoms related to hangover caused by hangover or acute alcoholism can be prevented, improved or relieved.

Description

Technical Field

[0001] The present invention belongs to the technical field of dietary or nutritional supplements, and particularly relates to methods and compositions for relieving hangover and / or preventing or improving hangover, as well as their related applications in preparing foods, beverages, nutritional supplements, and animal feeds for relieving hangover and / or preventing or improving hangover. Background Art

[0002] In today's society, drinking is an important behavior in human life. People generally believe that a small amount of alcohol can relieve anxiety and make people feel comfortable. However, long-term or excessive drinking at one time can cause great harm to the human body. Many people will experience hangover due to frequent and excessive drinking, which will affect their normal life the next day. There are even many cases where health is damaged due to long-term bad drinking habits.

[0003] Alcohol hangover (also referred to as "hangover" hereinafter) refers to various unpleasant physiological and psychological effects after drinking ethanol as seen in wine, beer, and distilled spirits. Hangover symptoms usually appear several hours after the intoxicating effect of alcohol begins to subside, such as after waking up from sleep after heavy drinking. The symptoms of hangover may 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 also include cognitive blurring, reduced motor ability, hematological changes, and hormonal changes. The accumulation of acetaldehyde, changes in glucose metabolism, dehydration, metabolic acidosis, disordered prostaglandin synthesis, increased cardiac output, vasodilation, sleep deprivation, and malnutrition are considered factors causing hangover symptoms, although the exact causes have not been fully elucidated.

[0004] Hangover can lead to absenteeism from work or school, weaken work ability, result in poor work performance, decreased productivity, and poor academic performance of students. Hangover may also pose safety problems because the symptoms of hangover may weaken an individual's ability to safely operate a vehicle, heavy equipment, or potentially dangerous tools.

[0005] Alcohol is mainly metabolized and detoxified by the liver. After entering the human body, it will increase the burden on 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 of humans, and has an adverse effect on the human nervous system. Therefore, long-term or excessive drinking will greatly increase the probability of cardiovascular and cerebrovascular diseases. Drinking alcohol can also cause changes in a person's emotional state, including many negative emotions, including the depressed and depressive mental state after drinking, and the mechanism of its occurrence is not clear.

[0006] Given the social context of the drinking culture, the demand for products that relieve alcohol intoxication and alleviate hangover is increasing. Paraxanthine (also known as 1,7-dimethylxanthine) is a dimethyl derivative of xanthine. Paraxanthine has been observed in nature as a metabolite of caffeine in animals and humans. Caffeine is by far the most studied and widely used stimulant present in coffee and tea products; although their chemical structures are very similar, paraxanthine has improved effects compared to caffeine and does not have the adverse side effects of caffeine. 1-Methylxanthine is also known as 1-methyl-3H-purine-2,6-dione. There is currently no relevant research or report on the relationship between paraxanthine or 1-methylxanthine and relieving alcohol intoxication, preventing or improving hangover, or treating, alleviating or improving symptoms related to hangover. Summary of the Invention

[0007] To achieve the above object, in one aspect, the present invention provides a method for relieving alcohol intoxication and / or preventing or improving hangover, the method comprising administering to a mammal a composition comprising an effective amount of paraxanthine or 1-methylxanthine. In some embodiments, the composition may further comprise a pharmaceutically acceptable carrier. In some embodiments, paraxanthine is natural or synthetic.

[0008] In some embodiments, relieving alcohol intoxication and / or preventing or improving hangover includes increasing the tolerance of a subject to alcohol, reducing the intoxicating effect of alcohol in a drinking subject, sobering up a subject who has consumed alcohol, promoting the degradation of alcohol and acetaldehyde in a subject, activating alcohol metabolism in the liver tissue of a subject, improving or restoring alcohol-induced liver injury, improving alcohol-induced movement disorders, preventing, improving or alleviating adverse reactions or symptoms related to hangover or acute alcohol intoxication.

[0009] In some embodiments, the adverse reactions or symptoms related to hangover or acute alcohol intoxication are selected from one or more of the following: dizziness, headache, dehydration, congestion, stomachache, anorexia, nausea, vomiting, diarrhea, tremor, sweating, fatigue, pain, muscle spasm, cognitive decline, poor visual-spatial coordination, hallucination, negative mood or depression, acute alcohol-induced liver injury, cognitive blurring.

[0010] In some embodiments, relieving alcohol intoxication and / or preventing or improving hangover is achieved by increasing the activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reducing the oxidative stress on the liver caused by metabolizing alcohol.

[0011] In some embodiments, the composition can be used as a mild mood enhancer or relaxant for a subject experiencing hangover.

[0012] In some embodiments, the composition is administered before, during or after drinking alcohol.

[0013] In some embodiments, the composition is formulated in the form of suppositories, tablets, pills, granules, powders, films, injections, capsules, aerosols, spirits, tinctures, tonics, solutions, liquid suspensions or syrups.

[0014] In some embodiments, the composition is prepared as a food, beverage, nutritional supplement, or animal feed.

[0015] In some embodiments, the composition is administered orally, intravenously, intramuscularly, intraperitoneally, or sublingually. In some embodiments, the composition is in a solid or liquid formulation, preferably in a solid oral dosage form.

[0016] In some embodiments, paraxanthine or 1-methylxanthine is formulated to be administered in an amount of 2 - 800 mg per day. In some embodiments, 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.

[0017] In another aspect, the present invention provides a composition comprising paraxanthine or 1-methylxanthine, which composition is for relieving alcohol intoxication and / or preventing or ameliorating a hangover. In some embodiments, the composition may further comprise a pharmaceutically acceptable carrier. In some embodiments, paraxanthine is natural or synthetic.

[0018] In some embodiments, relieving alcohol intoxication and / or preventing or ameliorating a hangover includes increasing the alcohol tolerance of a subject, reducing the alcohol intoxication effect of a drinking subject, sobering up a subject who has consumed alcohol, promoting the degradation of alcohol and acetaldehyde in the subject's body, activating alcohol metabolism in the subject's liver tissue, improving or restoring alcohol-induced liver injury, improving alcohol-induced movement disorders, preventing, ameliorating or alleviating adverse reactions or hangover-related symptoms caused by a hangover or acute alcohol intoxication.

[0019] In some embodiments, the adverse reactions caused by a hangover or acute alcohol intoxication or the hangover-related symptoms are selected from one or more of the following: dizziness, headache, dehydration, congestion, stomachache, anorexia, nausea, vomiting, diarrhea, tremors, sweating, fatigue, pain, muscle spasms, cognitive decline, poor visuospatial coordination, hallucinations, negative mood or depression, acute alcohol-induced liver injury, mental confusion.

[0020] In some embodiments, relieving alcohol intoxication and / or preventing or ameliorating a hangover is achieved by increasing the activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reducing the oxidative stress on the liver caused by alcohol metabolism.

[0021] In some embodiments, the composition can be used as a mild mood enhancer or relaxant for subjects experiencing a hangover.

[0022] In some embodiments, the composition is administered before, during, or after alcohol consumption.

[0023] 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.

[0024] In some embodiments, the composition is in a solid preparation or a liquid preparation, preferably in a solid oral dosage form.

[0025] In some embodiments, the composition is prepared as a food, beverage, nutritional supplement, or animal feed.

[0026] In some embodiments, paraxanthine or 1-methylxanthine is formulated to be administered in an amount of 2 - 800 mg per day. In some embodiments, 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.

[0027] In another aspect, the present invention provides the use of paraxanthine or 1-methylxanthine in the preparation of a composition for relieving alcohol intoxication and / or preventing or improving a hangover. In some embodiments, paraxanthine is natural or synthetic.

[0028] In some embodiments, relieving alcohol intoxication and / or preventing or improving a hangover includes increasing the alcohol tolerance of a subject, reducing the alcohol intoxication effect of a drinking subject, sobering up a subject who has consumed alcohol, promoting the degradation of alcohol and acetaldehyde in a subject's body, activating alcohol metabolism in a subject's liver tissue, improving or restoring alcohol-induced liver injury, improving alcohol-induced movement disorders, preventing, improving, or alleviating adverse reactions or hangover-related symptoms caused by a hangover or acute alcohol poisoning.

[0029] In some embodiments, the adverse reactions or hangover-related symptoms caused by a hangover or acute alcohol poisoning are selected from one or more of the following: dizziness, headache, dehydration, congestion, stomachache, anorexia, nausea, vomiting, diarrhea, tremor, sweating, fatigue, pain, muscle spasm, cognitive decline, poor visual-spatial coordination, hallucination, negative mood or depression, acute alcohol-induced liver injury, cognitive blurring.

[0030] In some embodiments, relieving alcohol intoxication and / or preventing or improving a hangover is achieved by increasing the activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reducing the oxidative stress on the liver caused by alcohol metabolism.

[0031] In some embodiments, the composition can be used as a mild mood enhancer or relaxant for a subject experiencing a hangover.

[0032] In some embodiments, the composition is administered before, during, or after alcohol consumption.

[0033] 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.

[0034] In some embodiments, the composition is in a solid or liquid formulation, preferably in a solid oral dosage form.

[0035] In some embodiments, the composition is prepared as a food, beverage, nutritional supplement, or animal feed.

[0036] In some embodiments, paraxanthine or 1-methylxanthine is formulated to be administered in an amount of 2 - 800 mg per day. In some embodiments, 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.

[0037] In some embodiments, paraxanthine or 1-methylxanthine accounts for 30%, 40%, 50%, 60% by weight of the composition, or even less.

[0038] The Summary of the Invention is provided to introduce a selection of concepts in a simplified form that will be further described in the Detailed Description below. The Summary of the Invention 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. Brief Description of the Drawings

[0039] Figure 1 is the number of movements of each group of mice 2 h after alcohol consumption.

[0040] Figure 2 is the moving distance of each group of mice 2 h after alcohol consumption.

[0041] Figure 3 is the moving time of each group of mice 2 h after alcohol consumption.

[0042] Figure 4 is the average moving speed of each group of mice 2 h after alcohol consumption.

[0043] Figure 5 is the number of stops of each group of mice 2 h after alcohol consumption.

[0044] Figure 6 It is the stagnation time of each group of mice 2 hours after drinking alcohol.

[0045] Figure 7 It is the plasma ethanol concentration of each group of mice 2 hours after drinking alcohol.

[0046] Figure 8 It is the plasma acetaldehyde concentration of each group of mice 2 hours after drinking alcohol.

[0047] Figure 9 It is the plasma ALT concentration of each group of mice 2 hours after drinking alcohol.

[0048] Figure 10 It is the plasma AST concentration of each group of mice 2 hours after drinking alcohol.

[0049] Figure 11 It is the plasma ADH enzyme activity of each group of mice 2 hours after drinking alcohol.

[0050] Figure 12 It is the plasma ALDH enzyme activity of each group of mice 2 hours after drinking alcohol.

[0051] Figure 13 It is the MDA level of each group of mice.

[0052] Figure 14 It is the GSH level of each group of mice.

[0053] Figure 15 It is the SOD level of each group of mice.

[0054] Figure 16 It is the TNF-α level of each group of mice.

[0055] Figure 17 It is the IL-6 level of each group of mice. Detailed Embodiments

[0056] Reference will now be made in detail to the preferred embodiments of the present invention, and further examples thereof will be described. Although the present invention will be described in connection with the preferred embodiments, it should be understood that they are not intended to limit the present invention to these embodiments. On the contrary, the present invention is intended to cover alternatives, modifications, and equivalents, which may be included within the spirit and scope of the present invention as defined by the claims.

[0057] As used herein, the term "or" is intended to include "and" and "or". In other words, the term "or" may also be replaced by "and / or".

[0058] As used herein, unless the context clearly indicates otherwise, the singular forms "a / an" and "the" are intended to also include the plural forms.

[0059] As used herein, the term "comprising" or "including" or variations thereof refers to the case where the term is used in its non-limiting sense, meaning including the items following the word, but not excluding items not specifically mentioned. It also includes the more restrictive verbs 'consisting essentially of' and 'consisting of'.

[0060] 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 may be suffering from an ailment or other disease, but the animal does not need to be sick 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 invention are equally applicable to veterinary medicine, for example, for treating domesticated species such as canines, felines, murine, and various other pets; farm animals such as cows, horses, sheep, goats, pigs, etc.; and wild animals such as non-human primates in the wild or in zoos.

[0061] As used herein, the term "administer" refers to the process of delivering the disclosed composition or active ingredient to a subject. The compositions of the present invention are preferably administered by routes such as oral, intravenous, intramuscular, intraperitoneal, or sublingual administration, but can also be administered by other conventional routes to achieve the desired effect. The compositions of the present invention can be administered before, during, and / or after alcohol consumption.

[0062] As used herein, the term "effective amount" refers to the amount required to achieve the effects taught herein. The effective amounts herein include, but are not limited to, the amount necessary for relieving alcohol intoxication and / or preventing or improving a hangover, and / or increasing tolerance to alcohol, sobering a subject who has consumed alcohol, promoting the degradation of alcohol and acetaldehyde in the body, activating alcohol metabolism in liver tissue, improving or restoring liver function, improving alcohol-induced dyskinesia, preventing or alleviating the adverse reactions caused by a hangover or acute alcohol intoxication, preventing or alleviating the injuries or symptoms caused by chronic alcoholism, and / or increasing the activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reducing the oxidative stress on the liver caused by alcohol metabolism. According to the present disclosure, a suitable single-dose size is a dose that can achieve the above effects when administered one or more times within a suitable time period.

[0063] As used herein, the term "pharmaceutically acceptable" means pharmaceutically, physiologically, nutritionally, and dietetically acceptable, and refers to those compositions or reagents, materials or combinations of compositions and / or their dosage forms within the scope of reasonable medical judgment, which are suitable for contact with the tissues of humans and animals, are compatible with the other components of the composition, have no excessive toxicity, irritation, allergic reaction or other problems or complications, and are commensurate with a reasonable benefit / risk ratio.

[0064] As used herein, the term "alcohol hangover" or "hangover" refers to an unpleasant physical condition manifested by the ingestion of alcoholic beverages, which may be accompanied by symptoms such as nausea, vomiting, headache, dizziness, tremors, fatigue, muscle cramps, cognitive decline, poor visuospatial coordination, pain, hallucinations, shakiness, and / or sweating. It is generally understood that alcohol sickness is mainly caused by acetaldehyde produced during the metabolism of ethanol after the ingestion of alcoholic beverages. For example, a hangover can refer to the above-mentioned condition that occurs within 24 hours after 10 hours of starting the ingestion of alcoholic beverages.

[0065] Paraxanthine or 1-methylxanthine and / or compositions containing the same are disclosed and their use for attenuating the effects of ethanol (or alcohol). Paraxanthine or 1-methylxanthine can be synthesized, or can be isolated from natural sources or by fermentation. Paraxanthine or 1-methylxanthine isolated from these sources can be purified to a purity of 95% or higher. Optionally, less purification can be used such that paraxanthine or 1-methylxanthine accounts for 50% of the substance, or even less. In some embodiments, it may be preferred to utilize paraxanthine or 1-methylxanthine isolated from natural sources, which may include other homologues, analogues, or derivatives of paraxanthine commonly found in paraxanthine or 1-methylxanthine sources. Paraxanthine analogues may include, but are not limited to, caffeine, methylcaffeine, theobromine, theophylline, liberine, and methylliberine, as well as variants thereof.

[0066] In certain embodiments, paraxanthine or 1-methylxanthine can be combined with one or more other compounds (e.g., other active ingredients) to provide a variety of beneficial effects in an individual. By varying the dose of paraxanthine or 1-methylxanthine and / or the compounds combined therewith, various physiological effects can be selected. The composition can primarily provide a single benefit or can provide multiple benefits simultaneously. In certain embodiments, paraxanthine or 1-methylxanthine is combined with one or more additional active ingredients selected from: gallic acid, (+)-catechin (C), (-)-epicatechin (EC), (+)-gallocatechin (GC), (-)-epigallocatechin (EGC), (-)-catechin gallate (CG), (-)-gallocatechin gallate (GCG), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG), glycerides, propylene glycol, lauroyl polyethylene glycol, lauroyl polyethylene glycol derivatives, bioperine co-crystallization products, piperine, black pepper, bergamottin, dihydroxybergamottin (CYP3A4), flavonoids (naringin, hesperidin, nobiletin, tangeretin, quercetin), pterostilbene, luteolin, phytosome, salicin, fish oil, oxylipins, tart cherry, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (avocado-soybean unsaponifiables), cetyl myristoleate, Dolichos falcate, triterpenoids, Acacia catechu, Andrographis paniculata, Scutalleria baicalensis, agmatine sulfate, Stinging Nettle, Sea Buckthorn, curcumin, Cissus quadrilateral, Boswellia serrata, Wasabia japonica (Wasabi extract for tea tree essential oil), Emu Oil, Arnica, Mangifera indica L.)(Anacardiaceae), Lagenaria breviflora, Zingiber officinale (ginger & gingerols / shogaols), hoodia gordonii, caffeine, yohimbine, synephrine, sinapine, theobromine, flavenoids, tocopherols, theophylline, alpha-yohimbine, conjugated linoleic acid (CLA), octopamine, evodiamine, passionflower, red pepper, chili pepper, raspberry ketone, Commiphora mukul, green tea, guarana, kola nut, beta-phenethylamines, Acacia rigidula, forskolin (Coleus forskohlli), theophylline, synephrine, yohimbine, rhodiola, Withania somnifera, ginseng, ginkgo biloba, Siberian ginseng, Astragalus membranaceus, Glycyrrhiza glabra, green tea, Ganoderma lucidum, dehydroepiandrosterone (DHEA), pregnenolone, tyrosine, N-acetyl-tyrosine, glucuronolactone, taurine, acetyl-L-carnitine, 5-hydroxytryptophan, tryptophan, phenethylamines, Sceletium tortuosum (and mesembrine alkaloids), Dendrobium sp., Acacia rigidula, PQQ (pyrroloquinoline quinone), ubiquinone (01), nicotinamide riboside, picamilon, huperzine A (Huperzia serrata) or Huperzia serrata, levodopa, Mucuna pruriens, and forskolin (Coleus forskohlli), 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, and combinations thereof.

[0067] In some embodiments, paraxanthine or 1-methylxanthine can be used at lower dosage levels and / or in combination with a compound that modulates or antagonizes its activity.

[0068] When administered to a subject experiencing hangover symptoms, the paraxanthine or 1-methylxanthine of the present invention and / or a composition comprising the same results in the alleviation of at least one of the following symptoms: dizziness, headache, dehydration, congestion, stomach ache, anorexia, nausea, vomiting, diarrhea, shakiness, sweating, fatigue, pain, muscle cramps, cognitive decline, poor visuospatial coordination, hallucinations, negative mood or depression, acute alcoholic liver injury, mental fogginess.

[0069] In certain embodiments, the composition is administered to a subject before alcohol intake. In an exemplary embodiment, the subject has a history of experiencing a hangover after alcohol intake. In other embodiments, the composition is administered to the subject during alcohol intake. In additional embodiments, the composition is administered to the subject at the onset of hangover symptoms. Hangover symptoms include those associated with a hangover as described above.

[0070] According to certain embodiments, the composition is administered in combination with one or more treatments or therapies. In an exemplary embodiment, the one or more treatments or therapies are selected from: fluids, electrolytes, caffeine, and / or non-opioid analgesics.

[0071] In some embodiments, the paraxanthine or 1-methylxanthine of the present invention and / or a composition comprising the same can be formulated into a composition together with a dietarily or pharmaceutically acceptable carrier. The above carriers include those non-toxic compatible substances commonly used in health foods, dietary supplements, 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, etc.

[0072] In some embodiments, the paraxanthine or 1-methylxanthine of the present invention and / or a composition comprising the same can be administered together with other supplements, such as vitamins, minerals, nootropics, and other supplements known in the art.

[0073] The method of the present invention comprises administering at least 1 mg, typically 2 - 800 mg, 5 - 800 mg, preferably 10 - 700 mg, 15 - 600 mg, 20 - 550 mg, 25 - 500 mg, 30 - 400 mg, 20 - 400 mg of paraxanthine or 1-methylxanthine per day, depending on the specific formulation and form. The amount to be administered can also vary according to factors such as the sensitivity of the subject, age, gender, and body weight, idiosyncratic reactions, etc. One or more doses can be administered once or multiple times per day within any time period or at a suitable frequency. For example, an effective dose can be administered daily for one day, several days, multiple days, or indefinitely.

[0074] The following examples illustrate selected embodiments of the present invention and are not meant to limit the scope of the present invention. Example 1

[0075] In this example, the effect of paraxanthine on hangover after drinking was studied using a mouse acute alcohol withdrawal model.

[0076] Experimental animals: Twenty-four 6-8-week-old C57BL / 6J wild-type mice weighing 20 ± 2 g were selected. The mice were housed in a temperature- and humidity-controlled animal room at an environmental temperature of 22°C ± 2°C and a humidity of 50 ± 5%, with a 12-hour light-dark cycle. Before the experiment, the mice were allowed to acclimatize to the environment for one week, during which they had free access to water and food. After one week, the mice were randomly divided into a control group, a model group, and an experimental group (paraxanthine, 50 mg / kg), with 8 mice in each group.

[0077] Animal intervention: The experiment was carried out after the pre-breeding period. The control group of mice was administered distilled water (0.6 g / kg), and the model group and the experimental group of mice were respectively administered absolute ethanol (0.6 g / kg) and the corresponding dose of paraxanthine by gavage. The paraxanthine was administered 30 minutes before the administration of ethanol in each experimental group, and the observation experiment was carried out 2 hours after the administration of ethanol.

[0078] Animal observation: The Open-field method was used to observe the spontaneous exploration ability and behavior of mice in a new environment. A single mouse was placed in a separate opaque container (40 cm * 70 cm * 40 cm), and its real-time activities were recorded by video. Behavioral analysis was performed using ANY-maze software, and the measured indicators included the number of movements, movement distance, movement time, average movement speed, number of stops, and stop time.

[0079] Sample collection and processing: After the observation experiment, blood (about 0.5 mL) was collected from the mice, and the blood samples were stored in EP tubes containing NaF to prevent alcohol degradation and stored at -80°C if necessary. The blood samples were centrifuged at 4°C and 3000 rpm for 10 minutes, and the upper serum was collected for detecting the concentrations of ethanol, acetaldehyde, as well as ALT and AST. After blood collection, the mice were euthanized with CO2, the liver was dissected, equal masses of liver tissue were taken, and homogenized with PBS at a mass ratio of 1:9. The specimens were lysed, centrifuged at 4°C and 10,000 rpm for 10 minutes, and the activities of ADH and ALDH in the supernatant were detected.

[0080] Statistical analysis: Graphpad 10.0 software was used for data analysis, and the result data were expressed as standard deviation (x ± s). Two-way ANOVA test was used for significant analysis. Experimental results:

[0081] Figure 1 It is the number of movements of each group of mice 2 hours after drinking alcohol. From Figure 1 It can be seen that the number of movements of the model group mice 2 hours after drinking alcohol decreased by 52.2% compared with the control group; while the number of movements of the experimental group that was administered paraxanthine to the alcohol-drinking mice recovered, and only decreased by 13.0% compared with the control group. Administering paraxanthine can improve the number of movements of mice after drinking alcohol.

[0082] Figure 2is the moving distance of each group of mice 2 hours after drinking. As can be seen from Figure 2 it that, for the model group of mice 2 hours after drinking, the moving distance decreased by 45.8% compared with the control group; while for the experimental group that administered paraxanthine to the drinking mice, the moving distance recovered, and only decreased by 3.6% compared with the control group. Administering paraxanthine can improve the moving distance of mice after drinking.

[0083] Figure 3 is the moving time of each group of mice 2 hours after drinking. As can be seen from Figure 3 it that, for the model group of mice 2 hours after drinking, the moving time decreased by 30.4% compared with the control group; while for the experimental group that administered paraxanthine to the drinking mice, the moving time recovered, and only decreased by 5.4% compared with the control group. Administering paraxanthine can improve the moving time of mice after drinking.

[0084] Figure 4 is the average moving speed of each group of mice 2 hours after drinking. As can be seen from Figure 4 it that, for the model group of mice 2 hours after drinking, the average moving speed decreased by 22.2% compared with the control group; while for the experimental group that administered paraxanthine to the drinking mice, the average moving speed recovered and was the same as the control group. Administering paraxanthine can improve the average moving speed of mice after drinking.

[0085] Figure 5 is the number of times of staying still of each group of mice 2 hours after drinking. As can be seen from Figure 5 it that, for the model group of mice 2 hours after drinking, the number of times of staying still increased by 100% compared with the control group; while for the experimental group that administered paraxanthine to the drinking mice, the number of times of staying still decreased, and even decreased by 16.7% compared with the control group. Administering paraxanthine can improve the number of times of staying still of mice after drinking.

[0086] Figure 6 is the staying still time of each group of mice 2 hours after drinking. As can be seen from Figure 6 it that, for the model group of mice 2 hours after drinking, the staying still time increased by 325% compared with the control group; while for the experimental group that administered paraxanthine to the drinking mice, the staying still time decreased and was only slightly higher than the control group. Administering paraxanthine can improve the staying still time of mice after drinking.

[0087] Figure 7 is the plasma ethanol concentration of each group of mice 2 hours after drinking. As can be seen from Figure 7 it that, for the model group of mice 2 hours after drinking, the ethanol concentration in the plasma reached 0.49%; while for the experimental group that administered paraxanthine to the drinking mice, the plasma ethanol concentration at the same time decreased, and decreased by 18.4% compared with the model group. Administering paraxanthine can improve the plasma ethanol concentration of mice after drinking and accelerate the metabolism of ethanol.

[0088] Figure 8 is the plasma acetaldehyde concentration of each group of mice 2 hours after drinking. As can be seen from Figure 8It can be seen that in the model group of mice 2 hours after drinking, the acetaldehyde concentration in the plasma reached 119 nmol / L; while in the experimental group where paraxanthine was administered to the drinking mice, the plasma acetaldehyde concentration at the same time decreased, and it decreased by 44.5% compared to the model group. Administering paraxanthine can improve the plasma acetaldehyde concentration in mice after drinking.

[0089] Figure 9 It is the plasma ALT concentration of each group of mice 2 hours after drinking. From Figure 9 It can be seen that in the model group of mice 2 hours after drinking, the ALT concentration in the plasma increased to 167 U / L; while in the experimental group where paraxanthine was administered to the drinking mice, the plasma ALT concentration at the same time decreased, and it decreased by 52.1% compared to the model group. Administering paraxanthine can improve the plasma ALT concentration in mice after drinking.

[0090] Figure 10 It is the plasma AST concentration of each group of mice 2 hours after drinking. From Figure 10 It can be seen that in the model group of mice 2 hours after drinking, the AST concentration in the plasma increased to 343 U / L; while in the experimental group where paraxanthine was administered to the drinking mice, the plasma AST concentration at the same time decreased, and it decreased by 56.9% compared to the model group. Administering paraxanthine can improve the plasma AST concentration in mice after drinking.

[0091] Figure 11 It is the plasma ADH enzyme activity of each group of mice 2 hours after drinking. From Figure 11 It can be seen that in the model group of mice 2 hours after drinking, the ADH in the plasma increased by 270% compared to the control group; while in the experimental group where paraxanthine was administered to the drinking mice, the ADH further increased, and it increased by 330% compared to the control group. Administering paraxanthine can further activate ADH in mice after drinking and help with ethanol metabolism.

[0092] Figure 12 It is the plasma ALDH enzyme activity of each group of mice 2 hours after drinking. From Figure 12 It can be seen that in the model group of mice 2 hours after drinking, the ALDH in the plasma increased by 133.3% compared to the control group; while in the experimental group where paraxanthine was administered to the drinking mice, the ALDH was the same as the control group. Administering paraxanthine can maintain the ALDH enzyme activity in mice after drinking at a certain level and help with acetaldehyde metabolism.

[0093] In the embodiments of the present invention, administering paraxanthine to mice can improve alcohol-induced motor disorders, increase the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), promote the degradation of alcohol and acetaldehyde in the body, and have a certain positive effect on relieving hangover after drinking. Example 2

[0094] In this example, through a chronic alcohol-drinking mouse model, the effect of paraxanthine on the liver oxidative stress caused by drinking was studied.

[0095] Experimental animals: Twenty-four 6-8-week-old C57BL / 6J wild-type mice weighing 20 ± 2 g were selected. They were housed in a temperature- and humidity-controlled animal room at 22°C ± 2°C and 50 ± 5% humidity, with a 12-hour light-dark cycle. The mice were allowed to acclimatize to the environment for one week before the experiment and had free access to water and food. After one week, they were randomly divided into a control group, a model group, and an experimental group (paraxanthine, 5 mg / kg), with 8 mice in each group.

[0096] Animal intervention: The experiment started after the pre-breeding was completed. During the experiment, the feeding conditions of the control group remained unchanged, while the model group and the experimental group were changed to freely drink a 5% aqueous alcohol solution for 7 days. The model group and the experimental group were respectively intragastrically administered the corresponding doses of the solvent and paraxanthine at a fixed time every day.

[0097] Sample collection and processing: Two hours after the administration of paraxanthine on the 7th day, the mice were euthanized with CO2, and the liver and kidneys were removed and weighed to calculate the liver / kidney organ coefficients. Liver tissue of the same mass and the same part was taken for index detection, homogenized with PBS at a mass ratio of 1:9, and the samples were stored in liquid nitrogen if necessary. The specimens were lysed to lyse cells, centrifuged at 4°C and 3000 g for 15 minutes, and malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), TNF-α, and IL-6 in the supernatant were detected.

[0098] Statistical analysis: Graphpad 10.0 software was used for data analysis. The result data was expressed as the standard deviation (x ± s), and two-way ANOVA test was used for significant analysis. Experimental results:

[0099] Figure 13 This is the MDA level of each group of mice. As Figure 13 can be seen, during the continuous alcohol consumption of the model group mice, the MDA level in the liver increased significantly, increasing by 10.25 times compared to the control group; while in the experimental group of mice administered paraxanthine while drinking alcohol, the increase in the liver MDA level of each drinking mouse was somewhat controlled, increasing by only 6.75 times compared to the control group. Administering paraxanthine can reduce the MDA level in the liver of mice after drinking alcohol and alleviate the liver oxidative stress caused by drinking.

[0100] Figure 14 This is the GSH level of each group of mice. As Figure 14 can be seen, during the continuous alcohol consumption of the model group mice, the GSH level in the liver decreased significantly, decreasing by 31.0% compared to the control group; while in the experimental group of mice administered paraxanthine while drinking alcohol, the GSH level in the liver increased somewhat, increasing by 11.3% compared to the control group. Administering paraxanthine can increase the GSH level in the liver of mice after drinking alcohol and improve the liver antioxidant capacity.

[0101] Figure 15are the SOD levels of each group of mice. As can be seen from Figure 15 it, during the continuous alcohol consumption of the mice in the model group, the SOD level in the liver decreased significantly, by 39.05% compared to the control group; while in the experimental group where paraxanthine was administered to the alcohol-consuming mice, the liver SOD level increased to a certain extent, and it decreased by 19.34% compared to the control group. Administering paraxanthine can increase the SOD level in the liver of alcohol-consuming mice and improve the antioxidant capacity of the liver.

[0102] Figure 16 are the TNF-α levels of each group of mice. As can be seen from Figure 16 it, during the continuous alcohol consumption of the mice in the model group, the TNF-α level in the liver increased significantly, by 106.67% compared to the control group; while in the experimental group where paraxanthine was administered to the alcohol-consuming mice, the increase in the liver TNF-α level was inhibited to a certain extent, and it only increased by 26.67% compared to the control group. Administering paraxanthine can inhibit the TNF-α level in the liver of alcohol-consuming mice, indicating a relatively low level of liver inflammation.

[0103] Figure 17 are the IL-6 levels of each group of mice. As can be seen from Figure 17 it, during the continuous alcohol consumption of the mice in the model group, the IL-6 level in the liver increased significantly, by 39.4% compared to the control group; while in the experimental group where paraxanthine was administered to the alcohol-consuming mice, the increase in the liver IL-6 level was inhibited to a certain extent, and it only increased by 8.1% compared to the control group. Administering paraxanthine can inhibit the IL-6 level in the liver of alcohol-consuming mice, indicating a relatively low level of liver inflammation.

[0104] In this embodiment, administering paraxanthine to alcohol-consuming mice can reduce the oxidative stress brought about by alcohol metabolism in the liver, improve the antioxidant capacity of the liver, reduce the increased inflammation level due to alcohol damage to the liver, and improve liver function.

[0105] The present inventor has found that the composition containing paraxanthine of the present invention and the method of the present invention have a positive regulatory effect on relieving alcohol intoxication and / or preventing or improving a hangover, can increase the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), promote the degradation of alcohol and acetaldehyde in the body, reduce the oxidative stress brought about by alcohol metabolism in the liver, and reduce the harm of alcohol consumption.

[0106] Although specific embodiments and examples of the present invention have been described herein, those skilled in the art will understand that any modifications and changes can be made without departing from the principles of the present invention. The above embodiments and descriptions do not limit the scope of the present invention. Any combination of the embodiments of the present invention, as well as any obvious extensions or analogues thereof, are within the scope of the present invention. In addition, the present invention covers any arrangement aimed at achieving the same purpose, as well as all such changes and modifications that fall within the scope of the appended claims.

Claims

1. Use of paraxanthine or 1-methylxanthine in the preparation of a composition for relieving alcohol intoxication and / or preventing or improving hangover.

2. The use according to claim 1, wherein The relieving of alcohol intoxication and / or preventing or improving hangover includes increasing the alcohol tolerance of a subject, reducing the alcohol intoxication effect of a drinking subject, sobering up a subject who has consumed alcohol, promoting the degradation of alcohol and acetaldehyde in the subject's body, activating alcohol metabolism in the subject's liver tissue, improving or restoring alcohol-induced liver injury, improving alcohol-induced movement disorders, preventing, improving or alleviating the adverse reactions or hangover-related symptoms caused by hangover or acute alcohol intoxication.

3. The use according to claim 2, characterized in that, The adverse reactions caused by hangover or acute alcohol intoxication or the hangover-related symptoms are selected from one or more of the following: dizziness, headache, dehydration, congestion, stomachache, anorexia, nausea, vomiting, diarrhea, tremor, sweating, fatigue, pain, muscle spasm, cognitive decline, poor visual-spatial coordination, hallucination, negative emotion or depression, acute alcohol-induced liver injury, cognitive blurring.

4. The use according to any one of claims 1 to 3, characterized in that, The relieving of alcohol intoxication and / or preventing or improving hangover is achieved by increasing the activity of alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) and / or reducing the oxidative stress on the liver caused by alcohol metabolism.

5. The use according to any one of claims 1 to 3, characterized in that, The composition is administered before, during or after drinking.

6. The use according to any one of claims 1 to 3, 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.

7. The use according to any one of claims 1 to 3, characterized in that, The composition is in a solid preparation or a liquid preparation.

8. The use according to any one of claims 1 to 3, characterized in that, The paraxanthine or 1-methylxanthine is formulated to be administered in an amount of 2 - 800 mg per day.

9. Use according to any one of claims 1 to 3, characterized in that, The composition is administered orally, intravenously, intramuscularly, intraperitoneally or sublingually.

10. The use according to any one of claims 1 to 3, characterized in that, The paraxanthine is natural or synthetic.

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