Composition for maintaining or improving liver function

Abstract

To provide a composition that is suitable for maintaining or improving a liver function and excellent in reducing or mitigating hangovers or sickness caused by drinking.SOLUTION: The invention provides a composition for maintaining or improving a liver function containing β-caryophyllene in an effective amount. Also there are provided a composition for reducing or mitigating discomfort after drinking, a composition for reducing or mitigating hangovers or sickness caused by drinking, and a composition for improving at least one liver function enzyme value selected from a group consisting of γ-GTP, AST and ALT, where the compositions each contain the composition for maintaining or improving the liver function as a component.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a composition for maintaining or improving liver function, a composition for reducing or improving discomfort after drinking alcohol, a composition for reducing or improving hangovers or bad drunkenness, and a composition for improving the level of at least one liver function enzyme selected from the group consisting of γ-GTP, AST, and ALT. [Background technology]

[0002] Drinking alcoholic beverages affects physiological and psychological states, and even small amounts can be expected to have effects such as improving mood and shortening the time it takes to fall asleep.

[0003] On the other hand, excessive alcohol consumption can cause hangovers and other symptoms such as nausea, vomiting, headaches, and dizziness.

[0004] Alcohol is metabolized in the body via acetaldehyde to acetic acid by aldehyde dehydrogenase 2, and then broken down into carbon dioxide and water. If acetaldehyde is not metabolized sufficiently, its toxicity can cause a hangover or a bad hangover.

[0005] People who genetically lack aldehyde dehydrogenase 2 or have low enzyme activity are prone to experiencing hangovers or severe intoxication even after consuming small amounts of alcohol.

[0006] It has been proposed to use Garcinia indica to treat hangovers and other symptoms of intoxication (Patent Document 1). [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Patent Publication No. 2021-123578 Summary of the Invention [Problem to be solved by the invention]

[0008] An object of the present invention is to provide a composition which is suitable for maintaining or improving liver function and is excellent in reducing or improving hangovers or bad hangovers. [Means for solving the problem]

[0009] In order to solve the above problems, the inventors conducted intensive research and discovered that β-caryophyllene, a natural component contained in essential oils of plants such as spices and herbs, has the effect of maintaining or improving liver function, thereby completing the present invention.

[0010] That is, the present invention provides the compositions described below.

[0011] [1] A composition for maintaining or improving liver function, comprising an effective amount of β-caryophyllene.

[0012] [2] The composition described in [1] is for reducing or improving discomfort after drinking alcohol.

[0013] [3] The composition described in [1] is for relieving or improving a hangover or a hangover.

[0014] [4] The composition described in [1], which is for improving the level of at least one liver function enzyme selected from the group consisting of γ-GTP, AST, and ALT.

[0015] [5] The composition according to any one of [1] to [4], wherein the daily intake amount of the β-caryophyllene is 5 to 300 mg.

[0016] [6] The composition according to any one of [1] to [4], which is taken before drinking alcohol, after drinking alcohol, or the day after drinking alcohol.

[0017] [7] The composition according to any one of [1] to [4], which is for oral, pulmonary, nasal, sublingual, or transdermal administration. Effect of the Invention

[0018] According to the present invention, by using β-caryophyllene, a natural ingredient, it is possible to provide a composition that is suitable for maintaining or improving liver function and is excellent in reducing or improving hangovers or bad hangovers. [Brief description of the drawings]

[0019] [Figure 1] FIG. 1 is a graph showing the evaluation results of the effect of β-caryophyllene on alcohol drinking in Test Example 1. [Diagram 2] FIG. 2 is a graph showing the evaluation results of the effect of β-caryophyllene on alcohol drinking in Test Example 1. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] [Composition for maintaining or improving liver function] In one embodiment, the composition for maintaining or improving liver function of the present invention contains β-caryophyllene.

[0021] (β-caryophyllene) β-Caryophyllene is a natural volatile component contained in essential oils obtained from cloves and other plants of the Myrtaceae family, and is used as a flavoring agent that can also be used in food.

[0022] β-caryophyllene is a compound represented by the following formula 1.

[0023] [ka]

[0024] β-caryophyllene includes the following isomers, and is not limited thereto, but is preferably (-)-β-caryophyllene.

[0025] (-)-β-Caryophyllene: (1R,1β,4E,9α)-4,11,11-trimethyl-8-methylene-bicyclo[7.2.0]undec-4-ene (+)-β-Caryophyllene: (1S,4E,9R)-4,11,11-trimethyl-8-methylenebicyclo[7.2.0]undec-4-ene

[0026] β-caryophyllene may be obtained by extraction and / or purification from plants, may be obtained by synthesis, or may be a commercially available product, such as those manufactured by Takasago International Corporation, Tokyo Chemical Industry Co., Ltd., and Wako Pure Chemical Industries, Ltd.

[0027] β-caryophyllene may be in a free form or in the form of a pharma- ceutically acceptable salt or ester.

[0028] Examples of pharma- ceutically acceptable salts of β-caryophyllene include salts with inorganic or organic bases, or salts with basic amino acids. Examples of inorganic bases include alkali metal salts such as sodium and potassium; alkaline earth metal salts such as calcium and magnesium; ammonium salts; and aluminum salts. Examples of the organic base include primary amines such as ethanolamine; secondary amines such as diethylamine, diethanolamine, dicyclohexylamine, and N,N'-dibenzylethylenediamine; and tertiary amines such as trimethylamine, triethylamine, triethanolamine, pyridine, and picoline. Examples of basic amino acids include lysine, arginine, and ornithine.

[0029] Examples of β-caryophyllene esters include β-caryophyllene esters formed by esterifying the methyl group in β-caryophyllene with a carboxylic acid, such as 14-acetoxy-β-caryophyllene formed by esterifying the methyl group with a carboxylic acid.

[0030] Plants containing the above-mentioned β-caryophyllene are not particularly limited, but examples thereof include cloves (Syzygium aromaticum), hemp (Cannabis sativa), rosemary (Salvia rosmarinus), and hops (Humulus lupulus).

[0031] The part to be extracted is not particularly limited as long as the effects of the present invention are achieved, and may be any of the whole plant or a necessary part (flower, inflorescence, flower bud, bud, inflorescence, leaf, branch, branch and leaf, rhizome, root bark, root, bark, fruit, pericarp, legume, seed, etc.). The part to be extracted may be, for example, at least one selected from the group consisting of root, stem, leaf, and flower, preferably at least one selected from the group consisting of stem, leaf, and flower, and more preferably at least one selected from the group consisting of stem and flower.

[0032] The extraction method is not particularly limited as long as it can produce the effects of the present invention, and known methods such as continuous extraction, immersion extraction, countercurrent extraction, etc. can be used, and conventional extraction methods, purification methods, concentration methods, synthesis methods, dry powdering methods, etc. are employed. The extract may be a crude extract as it is, or may be a crude extract that has been further purified or concentrated.

[0033] As an example, the clove extract can be an extract obtained by immersing and extracting the stems or flowers of cloves in water and / or an organic solvent and filtering the residue, or the extract from which the solvent has been removed, or a fine powder of these, or the extract or the solvent-removed product dissolved, dispersed or diluted with an appropriate solvent, or a commercially available product can be used.

[0034] In the present specification, when using a plant extract, more specifically, as the extraction solvent, water (including hot water), alcohols such as methanol, ethanol, isopropanol, ethylene glycol, 1,3-butylene glycol, glycerin, etc., esters such as ethyl acetate, ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile, ethers such as diethyl ether and tetrahydrofuran, saturated hydrocarbons such as pentane, hexane, cyclopentane, cyclohexane, aromatic hydrocarbons such as toluene, halogenated hydrocarbons such as dichloromethane and chloroform, and other organic solvents such as dimethylformamide and dimethyl sulfoxide (which may all contain water) can be appropriately used, and may be any mixture of one or two of them. Among these solvents, water, ethanol, 1,3-butylene glycol, or a mixture thereof is preferred. The extracts described in the present specification can be obtained from various raw material companies, and are usually sold in a form including excipients, but are not limited thereto.

[0035] As an example, the extraction solvent for the clove extract is not limited as long as the effects of the present invention are achieved, but is preferably water, ethanol, or aqueous ethanol, and more preferably aqueous ethanol.

[0036] The content of β-caryophyllene is not particularly limited, but may be, for example, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.3% by mass or more, 0.5% by mass or more, 1% by mass or more, 3% by mass or more, 5% by mass or more, 10% by mass or more, 20% by mass or more, or 90% by mass or less, 50% by mass or less, 25% by mass or less, 10% by mass or less, 5% by mass or less, 3% by mass or less, 1% by mass or less, preferably 0.01 to 95% by mass, more preferably 0.05 to 70% by mass, even more preferably 0.1 to 50% by mass, and particularly preferably 0.5 to 30% by mass, based on the total amount of the composition.

[0037] [Application] The composition of the present invention is preferably used for maintaining or improving liver function. Although not limited thereto, the effect of maintaining or improving liver function can promote the metabolism of alcohol and reduce or improve discomfort after drinking. In the examples (test examples) described later, it has been confirmed that the composition of the present invention has a reducing or improving effect on discomfort after drinking when ingested by humans.

[0038] The discomfort felt after drinking alcohol is not particularly limited as long as it is a discomfort felt along with drinking alcohol, but examples include headache, nausea, nausea (upset stomach, heavy stomach, heartburn, etc.), palpitations, drowsiness, feeling unwell, fatigue, weakness, lethargy, diarrhea, loss of appetite, trembling, dry mouth, joint pain, etc.

[0039] As described above, the composition of the present invention is capable of reducing or ameliorating the discomfort felt after drinking alcohol, and therefore can be suitably used for reducing or ameliorating a hangover or a bad hangover.

[0040] The composition of the present invention can maintain or improve liver function, thereby improving the level of at least one liver function enzyme selected from the group consisting of γ-GTP, AST, and ALT.

[0041] In the present specification, hangover refers to a feeling of one or more of the above-mentioned discomforts the day after drinking alcohol. For example, but not limited to, hangover refers to discomfort that appears about 8 to 14 hours after drinking alcohol.

[0042] In addition, drunkenness refers to the feeling of one or more of the above-mentioned discomforts within a short period of time after drinking alcohol. For example, but not limited to, it refers to discomfort that appears about 2 to 6 hours after drinking alcohol.

[0043] The timing of ingestion of the composition of the present invention is not particularly limited, but from the viewpoint of achieving the effects of the present invention, examples include ingestion before drinking alcohol, after drinking alcohol, or the day after drinking alcohol.

[0044] Ingestion of the composition of the present invention before drinking alcohol or on a daily basis is suitable for the purpose of maintaining or improving liver function. Examples of the composition of the present invention include, but are not limited to, ingesting the composition of the present invention once or twice a day from several days before an event in which alcohol is consumed, ingesting once or twice a day the day before the event, ingesting immediately before the event, ingesting within 2 hours of drinking alcohol, ingesting within 1 hour of drinking alcohol, or ingesting within 30 minutes of drinking alcohol. Ingestion of the composition of the present invention in this way can maintain or improve liver function, leading to the reduction or improvement of discomfort after drinking alcohol. Alternatively, anxiety about the occurrence of discomfort after drinking alcohol can be reduced.

[0045] It is also suitable to take the composition of the present invention during an event where alcohol is consumed or immediately after drinking alcohol in order to maintain or improve liver function, etc. Although not limited thereto, when one or more of the above-mentioned discomforts are felt after drinking alcohol, taking the composition of the present invention can lead to an early reduction or improvement of the discomfort.

[0046] It is also preferable to take the composition of the present invention the day after drinking alcohol in order to maintain or improve liver function, etc. Although not limited thereto, when one or more of the above-mentioned discomforts are felt the day after drinking alcohol, taking the composition of the present invention can lead to an early reduction or improvement of the discomfort.

[0047] The composition of the present invention can be used, for example, by adding to or mixing with food, beverage, feed, or pet food. Alternatively, for example, it can be used as a beverage or food as it is. It can be used, but is not limited to, as a food or beverage that clearly or implicitly indicates that it maintains or improves liver function, reduces or improves discomfort after drinking alcohol, reduces or improves hangovers or bad drunkenness, etc., that is, as a health food, a functional food, a food for the sick, or a food for specified health uses.

[0048] Examples of claims relating to the functionality mentioned above include "measures for drinking parties," "drink before drinking," "drink after drinking," "supplement for drinkers," "supplement for drunkenness," "supplement for people who like alcohol," "supplement for people who want to enjoy themselves at a drinking party," "supplement for heavy drinkers," "supplement for toasting," "drinking too much," "drinking fatigue," "supplement for people concerned about their liver values," "for people who want to feel good the day after a drinking party," and similar claims.

[0049] In addition, even if the above-mentioned functional indication is not explicitly or implicitly indicated, it can be used as a so-called doctor's supplement provided by a doctor at a hospital and / or clinic. For example, it can be a supplement that can be suggested, prescribed, or selected by a person who has been examined for liver function at an internal medicine department or a pharmacy.

[0050] The composition of the present invention can be used, for example, orally, pulmonary, nasally, sublingually, or transdermally. In the examples described below, it has been confirmed that the composition of the present invention has an effect of reducing or improving discomfort after drinking alcohol when it is orally ingested by humans. Since β-caryophyllene contained in the composition of the present invention is a volatile component, the effect of the present invention can be achieved not only by oral ingestion, but also by nasal absorption or pulmonary absorption. In addition, the effect of the present invention can be achieved by retaining β-caryophyllene contained in the composition of the present invention in the oral cavity by a known method such as a sublingual tablet, an orally disintegrating tablet, a chewable tablet, or a candy, and absorbing it sublingually.

[0051] The composition of the present invention can be used in various formulation forms such as solid preparations (tablets, orally disintegrating tablets, sublingual tablets, granules, fine granules, powders, capsules, chewable tablets, candies, etc.), liquid preparations (syrups, suspensions, sprays, creams, gels, ointments), and liquid foods. When the composition of the present invention is prepared as a food composition, it can be produced in the same manner as known pharmaceutical preparations, for example, by mixing an active ingredient with a carrier such as an excipient acceptable for pharmaceuticals or foods, and then producing it using conventional means. The formulation form is not limited, but from the viewpoint of significantly exhibiting the effects of the present invention, it is preferable that it is a tablet, an orally disintegrating tablet, a chewable tablet, a candy, a granule, a powder, a spray, or a liquid.

[0052] For example, tablets can be prepared by mixing a powdered active ingredient with a pharma- ceutically acceptable carrier component (such as an excipient) and compressing the mixture, and confectionery tablets such as candy can be prepared by pouring the mixture into a mold. Tablets can also be sugar-coated to form sugar-coated tablets. Furthermore, tablets can be single-layer tablets or laminated tablets such as double-layer tablets.

[0053] Powdered granules such as granules may be prepared by various granulation methods (such as extrusion granulation, grinding granulation, dry compaction granulation, fluidized bed granulation, rolling granulation, and high-speed stirring granulation), and tablets can be prepared by an appropriate combination of the above-mentioned granulation methods and tableting methods (wet tableting, direct tableting), etc.

[0054] Capsules can be prepared by filling a capsule (soft or hard capsule) with a powdered agent (powder, granules, etc.) by a conventional method.

[0055] The liquid preparation can be prepared by dissolving or dispersing each component in an aqueous medium (purified water, purified water containing ethanol, etc.) which is a carrier component, filtering or sterilizing the mixture as necessary, filling the mixture into a predetermined container, and sterilizing the mixture. The carrier component in the liquid preparation is not particularly limited, but from the viewpoint of achieving the effects of the present invention, it is preferable that the carrier component is, for example, MCT oil (medium chain fatty acid oil).

[0056] The preferred dosage form of the solid preparation of the present invention is a capsule or a tablet, and a soft capsule is more preferred.

[0057] Soft capsules have a smooth surface and are easy to swallow, and are therefore preferred by users. Typical methods for producing soft capsules include the plate method, the rotary method, and the seamless method.

[0058] In the rotary method (punching method), a sheet-like capsule shell sandwiches the flowing filling contents and forms a capsule shape along the holes of a rotating cylindrical die. On the other hand, in the seamless method (dropping method), the capsule shell composition and contents are simultaneously discharged from multiple concentric nozzles to form a seamless capsule shape.

[0059] The base material for the soft capsule shell is not particularly limited, but starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinated gelatin, etc. can be used, with starch, gelatin, and succinated gelatin being preferred, and gelatin and succinated gelatin being more preferred. These may be used alone or in combination of two or more kinds.

[0060] The composition of the present invention can also be manufactured as liquid beverages such as soups, juices, fruit juice drinks, milk, dairy drinks, whey drinks, lactic acid bacteria drinks, tea drinks, alcoholic drinks, coffee drinks, carbonated drinks, soft drinks, water drinks, cocoa drinks, jelly drinks, sports drinks, and diet drinks; semi-solid foods such as pudding and yogurt; noodles, confectioneries, spreads, and the like.

[0061] When the composition of the present invention is prepared as a food composition, various food additives may be blended therein, such as antioxidants, colorants, flavorings, seasonings, sweeteners, acidulants, pH adjusters, quality stabilizers, preservatives, etc.

[0062] Furthermore, when the composition of the present invention is prepared primarily for sublingual absorption, a form that has a long retention time in the oral cavity is preferable, and the form may be a food formulation such as a troche, chewing gum, tablet candy, gummy candy, caramel, or the like, or an oral hygiene agent such as toothpaste (powder toothpaste, moisturizing toothpaste, toothpaste, water toothpaste, etc.) or mouthwash.

[0063] Furthermore, when the composition of the present invention is prepared primarily for pulmonary absorption, for example, a form that has a long residence time in the air is preferred, and this may include a method in which an inhalation liquid is administered using a nebulizer, a method in which an inhalation aerosol is sprayed using a nebulizer, or a method in which an inhalation powder is inhaled using an inhaler.

[0064] Although not limited, when the composition of the present invention is prepared mainly for pulmonary absorption, it is preferable to aerosolize the composition. In this specification, aerosol means a mixture of fine liquid or solid particles suspended in gas and the surrounding gas. The method of making the composition into an aerosol is not particularly limited, and the composition can be aerosolized by, for example, a nebulizer, a sprayer, or an inhaler.

[0065] When the composition of the present invention is prepared mainly for pulmonary absorption, it is preferable to aerosolize the composition using, for example, a nebulizer. The type of nebulizer is not particularly limited, and for example, jet type, ultrasonic type, compressor type, and mesh type nebulizers can be used. When the composition of the present invention is a liquid, for example, a soft mist inhaler may be used to aerosolize the composition. When the composition is a solid such as a powder, it is preferable to aerosolize the composition using, for example, a nebulizer or an inhaler and administer the composition. The composition may be processed into a dosage form suitable for the nebulizer or inhaler to be used. For example, an aerosol formulation, a dry powder formulation, and an inhalation suspension can be mentioned.

[0066] The particle size of the liquid or solid contained in the aerosol is not particularly limited, but is preferably 0.001 μm to 20 μm, more preferably 0.001 μm to 10 μm, and particularly preferably 0.001 μm to 5 μm.

[0067] When the composition of the present invention is prepared mainly for percutaneous absorption, it can be used by applying it to the site where discomfort occurs after drinking alcohol using a known liquid preparation such as a cream, gel, ointment, etc. Examples of such application include, but are not limited to, applying the liquid preparation to the temples or forehead when a headache occurs due to drinking alcohol, and applying the liquid preparation to the joints when joint pain occurs due to drinking alcohol.

[0068] The daily intake of β-caryophyllene for an adult can be appropriately determined depending on the individual's condition, body weight, sex, age, activity of the material, intake or administration route, intake or administration schedule, formulation form, or other factors. The intake of β-caryophyllene is, for example, preferably 5 mg or more, more preferably 10 mg or more, even more preferably 15 mg or more, and particularly preferably 20 mg or more. The intake of β-caryophyllene is, for example, preferably 300 mg or less, more preferably 250 mg or less, even more preferably 200 mg or less, and particularly preferably 150 mg or less. The intake amount of β-caryophyllene is preferably 5 to 300 mg, for example, 10 to 300 mg, 15 to 300 mg, 20 to 300 mg, 5 to 250 mg, 10 to 250 mg, 15 to 250 mg, 20 to 250 mg, 5 to 200 mg, 10 to 200 mg, 15 to 200 mg, 20 to 200 mg, 5 to 150 mg, 10 to 150 mg, 15 to 150 mg, and 20 to 150 mg.

[0069] In another embodiment, when the composition of the present invention is prepared mainly for pulmonary absorption, for example, in the case of a liquid formulation, it is preferable to ingest the composition at a rate of 1 mL to 10 mL / min for 3 to 20 minutes, and in the case of a solid formulation, it is preferable to ingest 1 to 2000 μg per administration using a nebulizer, inhaler, or the like.

[0070] The daily oral intake or dosage for an adult may be divided into 1 to 6 capsules, 1 to 4 capsules, 1 to 3 capsules, or 1 to 2 capsules depending on the dosage form. For example, if the formulation is a capsule, the dosage form may be divided into 1 to 6 tablets, 1 to 4 tablets, 1 to 3 tablets, or 1 to 2 tablets.

[0071] The composition of the present invention can be ingested or administered once or several times a day, usually 1 to 6 times a day, 1 to 3 times a day, 1 to 2 times a day, or at any period and interval, but once a day or once at the time of use is preferred. EXAMPLES

[0072] Next, the present invention will be specifically described with reference to examples, but the present invention is not limited to the following examples.

[0073] [Test Example 1. Evaluation of the effect of β-caryophyllene intake on drinking alcohol] Humans were administered β-caryophyllene and the effect it had on discomfort after drinking alcohol was evaluated.

[0074] Example 1. Preparation of a sample containing β-caryophyllene The β-caryophyllene-containing samples were prepared as follows. 10 mL of 80% pure β-caryophyllene and 10 mL of MCT oil were precisely weighed and mixed. The mixture was transferred to a glass container with a dropper and used as a β-caryophyllene-containing sample.

[0075] (Test Example 1. Confirmation test of the effect of β-caryophyllene on drinking alcohol) The specific test method is as follows. Twelve healthy adults were randomly selected as subjects, and the amount of alcohol consumed that would cause a hangover for each subject was confirmed in advance. On a separate day, each subject was given approximately 100 mg of the above-mentioned β-caryophyllene-containing sample before drinking, drank the amount of alcohol consumed that would cause a hangover for each subject, and completed a questionnaire the next morning. The β-caryophyllene-containing sample was taken sublingually. In this method of intake, the sample was absorbed sublingually and orally with saliva, and since β-caryophyllene is a volatile component, it could also be taken via the nose or lungs at the same time.

[0076] The effect on hangovers was evaluated using a rating system according to the following criteria: The occurrence of a hangover without taking the β-caryophyllene-containing sample was set as the standard. <Evaluation criteria> 1: No effect at all 2 points: Not very effective 3 points: I don't know 4 points: I felt the effect 5 points: Very effective The results are shown in Figure 1.

[0077] Furthermore, the subjects were asked to fill out a questionnaire about the effects they felt. The results are shown in Figure 2. The effects that were felt were the following seven items, and participants answered by checking the effect that applied to them. - Reduced stomach discomfort - Reduced stomach discomfort Reduced headaches No more nausea - Intense motivation subsided Reduced fatigue and weakness Other (free response)

[0078] As shown in Figure 1, taking β-caryophyllene was confirmed to have a positive effect on hangovers in more than 65% of subjects.

[0079] As shown in Figure 2, it was confirmed that ingesting β-caryophyllene can reduce unpleasant sensations such as heavy stomach, heartburn, headache, nausea, palpitations, fatigue, weakness, and lethargy after drinking alcohol. Although not limited to these, favorable effects were confirmed in more than 40% of subjects with heavy stomach, headache, and nausea. It was also confirmed that the reduction or improvement of such unpleasant sensations after drinking alcohol can reduce or improve hangovers or bad hangovers.

Claims

1. A composition for maintaining or improving liver function, comprising an effective amount of β-caryophyllene.

2. The composition according to claim 1, which is for reducing or ameliorating discomfort after drinking alcohol.

3. The composition according to claim 1, which is for relieving or ameliorating a hangover or a hangover.

4. The composition according to claim 1, which is used for improving the level of at least one liver function enzyme selected from the group consisting of γ-GTP, AST, and ALT.

5. 2. The composition of claim 1, wherein the daily intake of β-caryophyllene is from 5 to 300 mg.

6. The composition according to claim 1, which is taken before drinking alcohol, after drinking alcohol, or the day after drinking alcohol.

7. The composition of claim 1, which is for oral, pulmonary, nasal, sublingual or transdermal administration.

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