Composition for maintaining or improving liver function

Abstract

In order to provide a composition that is suitable for maintaining or improving liver function and exceptional in terms of mitigating or improving hangovers or feelings of sickness caused by drinking, provided is a composition for maintaining or improving liver function containing β-caryophyllene in an effective amount. Also provided are a composition for mitigating or improving discomfort after drinking, a composition for mitigating or improving hangovers or feelings of sickness caused by drinking, and a composition for improving at least one liver function enzyme value selected from the group consisting of γ-GTP, AST, and ALT, each of these compositions containing the aforementioned component.

Description

Composition for maintaining or improving liver function

[0001] The present invention relates to a composition for maintaining or improving liver function, a composition for alleviating or improving discomfort after drinking alcohol, a composition for alleviating or improving hangovers or bad hangovers, 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.

[0002] Consumption of alcoholic beverages affects physiological and psychological states, and even small amounts can be expected to improve mood and shorten 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 hangovers or a bad hangover.

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

[0006] The use of Garcinia indica has been proposed for treating hangovers and hangover symptoms (Patent Document 1).

[0007] Japanese Patent Application Laid-Open No. 2021-123578

[0008] An object of the present invention is to provide a composition that is suitable for maintaining or improving liver function and is excellent in reducing or improving hangovers or hangover symptoms.

[0009] In order to solve the above problems, the present inventors conducted extensive research and found 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, and thus completed the present invention.

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

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

[0012] [2] The composition according to [1], which is for reducing or improving discomfort after drinking alcohol.

[0013] [3] The composition according to [1], which is for alleviating or improving a hangover or a hangover.

[0014] [4] The composition according to [1], which is used to improve 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 of 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.

[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 sickness.

[0019] Fig. 1 is a graph showing the evaluation results of the effect of β-caryophyllene on alcohol consumption in Test Example 1. Fig. 2 is a graph showing the evaluation results of the effect of β-caryophyllene on alcohol consumption in Test Example 1.

[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 belonging to the Myrtaceae family, and is used as a flavoring agent that can also be used in foods.

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

[0023]

[0024] β-caryophyllene includes the following isomers, and is not particularly limited, 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-methylene-bicyclo[7.2.0]undec-4-ene

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

[0027] β-Caryophyllene may be in a free form or in the form of a pharmaceutically acceptable salt or ester.

[0028] Pharmaceutically acceptable salts of β-caryophyllene include, for example, 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 organic bases 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 a methyl group in β-caryophyllene with a carboxylic acid, such as 14-acetoxy-β-caryophyllene formed by esterifying a methyl group with a carboxylic acid.

[0030] The plants containing 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 it produces the effects of the present invention, and may be the whole plant or any necessary part (flower, inflorescence, flower bud, flower spike, 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 achieves the effects of the present invention, and known methods such as continuous extraction, immersion extraction, countercurrent extraction, etc. can be used, as well as conventional extraction methods, purification methods, concentration methods, synthesis methods, dry powdering methods, etc. 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 may be an extract obtained by immersing clove stems or flowers in water and / or an organic solvent and filtering the residue; a product obtained by removing the solvent from this extract; or a fine powder of these; or a product obtained by dissolving, dispersing, or diluting the extract or the product obtained by removing the solvent using an appropriate solvent; or a commercially available product may also be used.

[0034] In the present specification, when using a plant extract, more specifically, the extraction solvent may be water (including hot water), alcohols such as methanol, ethanol, isopropanol, ethylene glycol, 1,3-butylene glycol, and glycerin, 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, and cyclohexane, aromatic hydrocarbons such as toluene, halogenated hydrocarbons such as dichloromethane and chloroform, and organic solvents such as dimethylformamide and dimethyl sulfoxide (which may all contain water), or a mixture of any two or more of these solvents. Of these solvents, water, ethanol, 1,3-butylene glycol, or a mixture thereof is preferred. The extracts described herein are available from various raw material suppliers and are often sold in a form containing excipients, but are not limited thereto.

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

[0036] The content of β-caryophyllene is not particularly limited, and 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, or 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, or 1% by mass or less, relative to the total amount of the composition. The content is 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.

[0037] [Uses] The composition of the present invention is suitable for maintaining or improving liver function. Although not limited thereto, the effect of maintaining or improving liver function can promote alcohol metabolism and reduce or improve discomfort after drinking alcohol. In the examples (test examples) described below, when the composition of the present invention was administered to humans, it was confirmed that it reduced or improved discomfort after drinking alcohol.

[0038] The discomfort felt after drinking alcohol is not particularly limited as long as it is a discomfort felt in association with drinking alcohol, but examples include headache, nausea, nausea (upset stomach, heavy stomach feeling, 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 can reduce or improve the discomfort felt after drinking alcohol, and therefore can be suitably used to reduce or improve hangovers or sickness.

[0040] The composition of the present invention can exert an effect of improving the level of at least one liver function enzyme selected from the group consisting of γ-GTP, AST, and ALT by maintaining or improving liver function.

[0041] As used herein, hangover refers to one or more of the above-mentioned discomforts felt the day after drinking alcohol, including, but not limited to, discomfort that appears approximately 8 to 14 hours after drinking alcohol.

[0042] Furthermore, hangover refers to the sensation of one or more of the above-mentioned discomforts felt within a short period of time after drinking alcohol, for example, but not limited to, discomfort that appears approximately 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, it may be ingested, for example, before drinking alcohol, after drinking alcohol, or the day after drinking alcohol.

[0044] Ingesting the composition of the present invention before drinking alcohol or on a daily basis is suitable for purposes such as maintaining or improving liver function. Examples of such methods include, but are not limited to, ingesting the composition of the present invention once or twice a day starting several days before an event that involves drinking alcohol, ingesting it once or twice the day before the event, ingesting it immediately before the event, ingesting it within two hours of drinking alcohol, ingesting it within one hour of drinking alcohol, or ingesting it within 30 minutes of drinking alcohol. Ingesting the composition of the present invention in this manner can maintain or improve liver function, leading to a reduction or amelioration of discomfort after drinking alcohol, or reducing anxiety about discomfort after drinking alcohol.

[0045] Taking the composition of the present invention during an event where alcohol is consumed or immediately after drinking alcohol is also suitable for the purpose of maintaining or improving 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 early alleviation or improvement of the discomfort.

[0046] Taking the composition of the present invention the day after drinking alcohol is also suitable for the purpose of maintaining or improving 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 early alleviation 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, it can be used, for example, as a beverage or food as is. It can be used, but is not limited to, as a food or beverage that explicitly or implicitly claims to maintain or improve liver function, reduce or improve discomfort after drinking, reduce or improve hangovers or bad hangovers, etc., i.e., 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 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 drinking parties," "supplement for heavy drinkers," "supplement for toasting," "drinking too much," "drinking fatigue," "supplement for people who are concerned about their liver values," "for people who want to feel good the day after a drinking party," and similar claims.

[0049] Furthermore, even if the above-mentioned functional claims are not explicitly or implicitly indicated, they can be used as so-called doctor's supplements provided by doctors at hospitals and / or clinics, for example, supplements that can be suggested, prescribed, or selected by a person who has been examined for liver function at an internal medicine department or pharmacy.

[0050] The composition of the present invention can be used, for example, orally, via the lungs, via the nose, sublingually, or transdermally. In the examples described below, it was confirmed that the composition of the present invention, when orally ingested by humans, reduced or improved post-alcohol discomfort. Because β-caryophyllene contained in the composition of the present invention is a volatile component, the effects of the present invention can be achieved not only by oral ingestion but also by nasal or pulmonary absorption. Furthermore, the effects of the present invention can also be achieved by retaining β-caryophyllene contained in the composition of the present invention in the oral cavity and then sublingually absorbing it using known methods, such as sublingual tablets, orally disintegrating tablets, chewable tablets, or candy.

[0051] The composition of the present invention can be used in various dosage forms, such as solid preparations (tablets, orally disintegrating tablets, sublingual tablets, granules, fine granules, powders, capsules, chewable tablets, candy, 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 the active ingredient with a carrier such as an excipient acceptable for pharmaceuticals or foods, and then producing it using conventional means. The dosage form is not limited, but from the viewpoint of significantly exhibiting the effects of the present invention, tablets, orally disintegrating tablets, chewable tablets, candy, granules, powders, sprays, or liquid preparations are preferred.

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

[0053] Powdered granules such as granules may be prepared by various granulation methods (extrusion granulation, pulverization granulation, dry compaction granulation, fluidized bed granulation, tumbling granulation, high-speed stirring granulation, etc.), 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 powder (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.) as a carrier component, filtering or sterilizing the resulting mixture as necessary, filling the resulting mixture into a predetermined container, and sterilizing the resulting 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 liquid preparation be, 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 are preferred by users because they have a smooth surface and are easy to swallow. Common methods for manufacturing soft capsules include the flat 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 material and forms a capsule shape along the holes of a rotating cylindrical mold. On the other hand, in the seamless method (dropping method), the capsule shell composition and the filling material 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 may be starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinated gelatin, etc., 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.

[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, and preservatives.

[0062] Furthermore, when the composition of the present invention is prepared primarily for sublingual absorption, a form that is retained in the oral cavity for a long time is preferred, and the form may be a food product such as a troche, chewing gum, tableted candy, gummy candy, or caramel, or an oral hygiene product 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, a form that has a long residence time in the air is preferred, and this may include a method in which an inhalable liquid is administered using a nebulizer, a method in which an inhalable aerosol is sprayed using a nebulizer, or a method in which an inhalable powder is inhaled using an inhaler.

[0064] Although not limited thereto, when the composition of the present invention is prepared primarily for pulmonary absorption, it is preferable to aerosolize the composition. As used herein, aerosol refers to a mixture of minute liquid or solid particles suspended in gas and the surrounding gas. The method for converting the composition into an aerosol is not particularly limited, and the composition can be aerosolized using, for example, a nebulizer, a sprayer, or an inhaler.

[0065] When the composition of the present invention is prepared primarily for pulmonary absorption, it is preferably aerosolized using, for example, a nebulizer. The type of nebulizer is not particularly limited, and for example, jet, ultrasonic, compressor, or mesh nebulizers can be used. When the composition of the present invention is a liquid, for example, a soft mist inhaler may be used for aerosolization. Furthermore, when the composition is a solid, such as a powder, it is preferably aerosolized and administered using, for example, a nebulizer or inhaler. The composition may be processed into a dosage form appropriate for the nebulizer or inhaler to be used. Examples include aerosol formulations, dry powder formulations, and inhalation suspensions.

[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 primarily for transdermal absorption, it can be used by applying it to the site where discomfort occurs after drinking alcohol, for example, in the form of a known liquid such as a cream, gel, or ointment. Examples of such application include, but are not limited to, applying the liquid to the temples or forehead when drinking causes headache, and applying the liquid to the joints when drinking causes joint pain.

[0068] The daily intake amount of β-caryophyllene for an adult can be determined appropriately depending on the individual's condition, body weight, sex, age, activity of the material, intake or administration route, intake or administration schedule, formulation form, and other factors. The intake amount 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 amount 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, a liquid formulation is preferably ingested at a rate of 1 mL to 10 mL / min over 3 to 20 minutes, and a solid formulation is preferably ingested at a dose of 1 to 2000 μg per administration using a nebulizer, inhaler, or the like.

[0070] The oral intake or dosage for an adult per day 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 capsules, the dosage 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 taken or administered once to several times a day, typically 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.

[0072] Next, the present invention will be specifically explained by way of 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 β-caryophyllene was ingested by humans, and the effect on discomfort after drinking alcohol was evaluated.

[0074] Example 1 Preparation of a β-caryophyllene-containing sample A β-caryophyllene-containing sample was 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 equipped with a dropper and used as a β-caryophyllene-containing sample.

[0075] (Test Example 1: Test to confirm the effect of β-caryophyllene on alcohol consumption) 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 determined in advance. On a separate day, each subject ingested the above-mentioned β-caryophyllene-containing sample at a daily intake of approximately 100 mg of β-caryophyllene before drinking, consumed the amount of alcohol consumed that would cause a hangover for each subject, and completed a questionnaire the following morning. The β-caryophyllene-containing sample was ingested sublingually. In this ingestion method, in addition to being absorbed sublingually, it was also ingested orally with saliva, and because β-caryophyllene is a volatile component, nasal and pulmonary ingestion could also be performed simultaneously.

[0076] The effect on hangovers was evaluated using a rating system according to the following criteria. The standard was the occurrence of a hangover without taking the β-caryophyllene-containing sample. <Evaluation criteria> 1 point: No effect at all 2 points: Little effect 3 points: Unclear 4 points: Effect felt 5 points: Very effective The results are shown in Figure 1.

[0077] Furthermore, the subjects answered a questionnaire about the effects they felt. The results are shown in Figure 2. The effects they felt were divided into the following seven categories, and they answered by checking the appropriate effect. ・Reduced stomach upset ・Reduced stomach upset ・Reduced headache ・No more nausea ・Calmed intense urges ・Reduced fatigue and weakness ・Other (free response)

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

[0079] Furthermore, as shown in Figure 2, it was confirmed that ingestion of β-caryophyllene can reduce discomfort after drinking alcohol, such as heavy stomach upset, heartburn, headache, nausea, palpitations, fatigue, weakness, and lethargy. Although not limited to this, favorable effects were confirmed in 40% or more of the subjects with respect to heavy stomach upset, headache, and nausea. It was also confirmed that the reduction or improvement of such discomfort after drinking alcohol can result in the reduction or improvement of 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, for reducing or improving discomfort after drinking alcohol.

3. The composition according to claim 1, for use in alleviating 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. The composition of claim 1, wherein the daily intake of β-caryophyllene is 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.

Images