WO2006091010A1 - Composition comprising coenzyme q10 as effective ingredient - Google Patents

Composition comprising coenzyme q10 as effective ingredient Download PDF

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Publication number
WO2006091010A1
WO2006091010A1 PCT/KR2006/000605 KR2006000605W WO2006091010A1 WO 2006091010 A1 WO2006091010 A1 WO 2006091010A1 KR 2006000605 W KR2006000605 W KR 2006000605W WO 2006091010 A1 WO2006091010 A1 WO 2006091010A1
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WIPO (PCT)
Prior art keywords
alcohol
coenzyme qlo
eliminating
pharmaceutical composition
related disorders
Prior art date
Application number
PCT/KR2006/000605
Other languages
French (fr)
Inventor
Sang Mo Kang
Original Assignee
Eotech Co., Ltd
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Publication date
Priority claimed from KR1020060016560A external-priority patent/KR20060094875A/en
Application filed by Eotech Co., Ltd filed Critical Eotech Co., Ltd
Publication of WO2006091010A1 publication Critical patent/WO2006091010A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to a composition comprising coenzyme QlO as an effective ingredient. More particularly, the present invention relates to a pharmaceutical composition for eliminating and alleviating alcohol-related disorders comprising coenzyme QlO as an effective ingredient, a method of administering the composition, and a functional food using the composition.
  • Acetaldehyde is the major metabolite of alcohol, which is highly reactive and toxic. Since such acetaldehyde acts directly on the nervous system, resulting in the onset of various side effects, it is known to be responsible for most hangover symptoms (Sherif, S., Wahlstrom, G., Oreland, L.
  • acetaldehyde In addition to acetaldehyde, other toxic molecules are generated during alcohol metabolism, such toxic molecules being highly reactive oxygen-containing compounds known as "reactive oxygen species".
  • the reactive oxygen species which appear after alcohol consumption, release arachidonic acid from cells and induce cyclooxygenase-2 (hereinafter, referred to simply as "COX-2"), which is an enzyme synthesizing prostaglandins (hereinafter, referred to simply as "PG”) , resulting in the synthesis of prostaglandin E 2 (PGE 2 ) , causing pain.
  • COX-2 cyclooxygenase-2
  • PGE 2 prostaglandin E 2
  • hangover People suffer from effects after drinking alcohol collectively known as a "hangover" .
  • the main hangover symptoms are dizziness, headaches, and stomachaches (stomach irritation) , and other symptoms include fatigue, irritability, nausea, diarrhea, thirst, sleep disturbance, and chills
  • Coenzyme QlO which is a strong antioxidant, is known as Ubiquinone, and also as coenzyme Q, helping the activity of some enzymes. Also, this substance is a benzoquinone derivative having a CH 3 O group at positions 2 and 3, and is distributed ubiquitously in biological systems and contained in a large amount in the mitochondria of cells. Coenzyme QlO acts to accept electrons from flavin enzymes and non-heme-iron proteins and to transfer them to cytochrome b. The present inventors found that reactive oxygen species generated during the breakdown of alcohol and acetaldehyde induce COX-2 expression at a high level, which in turn produces PGE 2 , leading to hangover symptoms accompanied by pain.
  • coenzyme QlO which displays a strong antioxidant activity in the cytosol while reducing the leakage of electrons by acting on the mitochondrial electron transport chain, to be excellent in eliminating hangover symptoms .
  • the finding also includes the observ -:ion that when coenzyme QlO is taken in an effective amount of LO rag to 20 g before, during, after, or the day following alcohol consumption, it has excellent therapeutic effect s against alcohol-related disorders, thereby leading to the present invention.
  • the present invention aims to provide a pharmaceutical composition for eliminating and alleviating alcohol-related disorders comprising coenzyme QlO as an effective ingredient, a method of administering the composition, and a functional food using the composition.
  • the present invention provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders comprising coenzyme QlO as an effective ingredient.
  • the present invention also provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders comprising, in addition to coenzyme QlO, one or more selected from the group consist ing of squalene, vitamin E, peptides, gurume, which indicate low molecular weight molecules extracted from a fermented concentrate of fruits and vegetables, Hovenia dulcis T ; L:nb extract, Alnus japonica extract, and Pueraria Root extrac.
  • the present invention fur er provides a pharmaceutical composition for eliminating ai> ⁇ ⁇ > alleviating alcohol-related disorders comprising, in addition to coenzyme QlO, a cyclooxygenase-2 (COX-2) inhibitor, preferably one or more selected from the group consisting of non-steroidal antiinflammatory drugs (NSAIDs) , aspirin, acetaminophen, ibuprofen, naproxen, phenacetin, mefenamic acid and indomethacin, celecoxib, diclofenac, etodolac, fenoprofen, ketoprofen, ketoralac, oxaprozin, nabumetone, sulindac, tolmetin, and rofecoxib.
  • NSAIDs non-steroidal antiinflammatory drugs
  • the present invention further provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders, comprising coenzyme QlO in an effective amount of 10 mg to 20 g, preferably 50 mg to 1 g, the composition being taken before, during, after, or the day after alcohol consumption.
  • the present invention further provides a functional food comprising the pharmaceutical composition for eliminating and alleviating alcohol-related disorders, the food being taken as a side dish during alcohol consumption.
  • the present invention further provides a functional food comprising coenzyme QlO in an effective amount of 10 mg to 20 g, the food being taken as a side dish during alcohol consumption and preferably being taken before, during, after, or the day after alcohol consumption.
  • the present invention further provides a treatment method for eliminating and alleviating alcohol-related disorders including hangover symptoms and flushing, comprising taking the pharmaceutical composition comprising coenzyme QlO in an effective amount of 10 mg to 20 g before, during, after, or the day after alcohol consumption.
  • a treatment method for eliminating and alleviating alcohol-related disorders including hangover symptoms and flushing comprising taking the pharmaceutical composition comprising coenzyme QlO in an effective amount of 10 mg to 20 g before, during, after, or the day after alcohol consumption.
  • lipid peroxides are produced when cells are dosed with alcohol or acetaldehyde. This is due to the generation of reactive oxygen species upon acetaldehyde decomposition (Olin, K.L., Cherr, G.N., Rifkin, E., Keen, CL. Toxicology, 17:110 (1-3) ; 1-8, 1996).
  • the intracellular formation of reactive oxygen species may mediate, in addition to lipid peroxidation, COX-2 induction, resulting in the conversion of arachidonic acid into prostaglandin E 2 (PGE 2 ) , and the increased PGE 2 levels may cause pain associated with hangovers.
  • the present invention provides the use of coenzyme QlO as a hangover-eliminating substance, based on the aforementioned hangover mechanism.
  • the present invention provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders, comprising coenzyme QlO as an effective ingredient.
  • the present invention also provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders comprising, in addition to coenzyme QlO, another antioxidant.
  • Preferred antioxidants include squalene, vitamin E, and peptides, which may be used singly or in combination.
  • the pharmaceutical composition may further include a substance which is known to be effective in alleviating hangover symptoms by lowering acetaldehyde concentrations in the body. Examples of such substances include gurume, Hovenia dulcis Thurib extract, Alnus japonica extract, and Pueraria Root extract, which may be used singly or in combination.
  • the present invention further provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders further comprising an inhibitor against COX-2 induced by reactive oxygen species.
  • the COX-2 inhibitor is a non-steroidal anti-inflammatory drug (NSAID) .
  • NSAID non-steroidal anti-inflammatory drug
  • More preferred examples of COX-2 inhibitors include aspirin, acetaminophen, naproxen, ibuprofen, phenacetin, mefenamic acid and indomethacin, celecoxib, diclofenac, etodolac, fenoprofen, ketoprofen, ketoralac, oxaprozin, nabumetone, sulindac, tolmetin, and rofecoxib.
  • the pharmaceutical composition for eliminating and alleviating alcohol-related disorders comprises coenzyme QlO in an effective amount of 10 mg to 20 g, and preferably 50 mg to 1 g.
  • the composition is preferably taken before, during, after, or the day after alcohol consumption.
  • the present invention further provides the use of coenzyme QlO in the removal of reactive oxygen species before and after alcohol consumption.
  • the present invention further provides a treatment method for eliminating and alleviating alcohol-related disorders, comprising taking the coenzyme QlO.
  • coenzyme QlO is preferably taken along with another antioxidant, and is more preferably taken along with squalene, vitamin E, and peptides, which may be used singly or in combination. It is also preferable to take, in addition to the coenzyme QlO and antioxidant, substances known to be effective in alleviating hangover symptoms by lowering acetaldehyde concentrations in the body, that is, gurume, Hovenia dulcis Thunb extract, Alnus japonica extract and Pueraria Root extract, and the like, which may be used singly or in combination.
  • COX-2 inhibitor is preferably a non-steroidal anti-inflammatory drug (NSAID) .
  • COX-2 inhibitors including aspirin, acetaminophen, naproxen, ibuprofen, phenacetin, mefenamic acid and indomethacin, celecoxib, diclofenac, etodolac, fenoprofen, ketoprofen, ketoralac, oxaprozin, nabumetone, sulindac, tolmetin, and rofecoxib, are used singly or in combination.
  • the COX-2 inhibitors are more preferably taken during or before and after alcohol consumption, rather than being taken the day after alcohol consumption, at the time that hangover symptoms occur.
  • a supplement such as chitosan, vitamin complexes comprising vitamin Bl, B2, C, etc., or the like.
  • the coenzyme QlO is preferably taken before, during, after, or the day after alcohol consumption in a form contained in a pharmaceutical composition in an effective amount of 10 mg to 20 g.
  • the present invention further provides a functional food supplemented with the pharmaceutical composition for eliminating and alleviating alcohol-related disorders, the food being used as a side dish upon alcohol consumption.
  • the pharmaceutical composition for eliminating and alleviating alcohol-related disorders according to the present invention may be used independently or as a drug additive along with a pharmaceutically acceptable carrier or excipient.
  • carriers to be included in the pharmaceutical composition of the present invention are sufficiently known in the art, and may include thickeners, high fiber additives, capsulating agents, and lipids.
  • the pharmaceutical composition for eliminating and alleviating alcohol-related disorders according to the present invention may be administered by varying the dosage depending on the severity of the illness, the patient's age, sex, physical state, weight and diet, duration and mode of administration, rates of excretion of active agents, and the like.
  • the coenzyme QlO contained in the pharmaceutical composition of the present invention may be administered in a dosage of 0.1 mg to 0.2 g per kg of body weight via oral or parenteral routes.
  • FIGS. 1 and 2 are graphs showing that coenzyme QlO according to the present invention has an effect of inhibiting the production of lipid peroxides.
  • FIG. 3 is a graph showing the changes in plasma prostaglandin E 2 levels upon administration of alcohol alone.
  • FIG. 4 is a graph showing the changes in plasma prostaglandin E 2 levels upon administration of alcohol plus coenzyme QlO according to the present invention.
  • FIGS. 5 and 6 are photographs showing that coenzyme QlO according to the present invention has the effect of inhibiting flushing upon alcohol consumption.
  • FIGS. 7 and 8 are photographs showing that coenzyme QlO according to the present invention has the effect of inhibiting flushing upon alcohol consumption.
  • EXAMPLE 1 Measurement of in vivo lipid peroxide levels after coenzyme QlO administration
  • FIG. 1 shows the plasma levels of lipid peroxides (LPO) , wherein an open square indicates ethanol administration, and an open circle indicates ethanol plus coenzyme QlO administration.
  • FIG. 2 shows blood alcohol concentrations, wherein an open square indicates ethanol administration, and an open circle indicates ethanol plus coenzyme QlO administration.
  • LPO lipid peroxides
  • Blood PGE 2 levels were evaluated after alcohol ingestion, as follows. Rats weighing about 300 g were fasted for 12 hrs, and 3 g/kg of alcohol was then administered orally to the fasted rats. Blood samples were collected from the tail vein of rats at given time points, and blood PGE 2 levels were determined using a commercially available kit for PGE 2 measurement . Blood levels of alcohol and acetaldehyde were measured according to the same procedure as in Example 1.
  • FIG. 3 An open circle indicates blood PGE 2 concentrations, an open triangle indicates blood alcohol concentrations, and an open square indicates blood acetaldehyde concentrations .
  • PGE 2 levels started to increase immediately after alcohol ingestion, and the elevated PGE 2 levels were maintained even after 8 hrs, in which alcohol was not detected in the blood. It is clear from these results why hangover symptoms remain even 20 hrs after alcohol consumption.
  • coenzyme QlO was administered at a dosage of 1 g/kg. One third of the dosage was administered 1 hr before alcohol administration, and the remaining amount was administered in the form of being dissolved in alcohol.
  • the results are given in FIG. 4.
  • the coenzyme QlO administration was found to reduce blood PGE2 levels compared to the administration of alcohol alone, indicating that coenzyme QlO greatly inhibited PGE 2 production.
  • the blood levels of alcohol and acetaldehyde were slightly lower than those shown in FIG. 3, indicating that the ingested coenzyme QlO also quickly reduced the blood levels of alcohol and acetaldehyde.
  • hangover symptoms were evaluated in sixteen college students who experienced a hangover feeling every time they ingested a Korean traditional distilled alcohol liquor, "Soju", five times or more (amount of alcohol ingested: 80-120 ml). The subjects ingested approximately l ⁇ 0.5 bottles of Soju, giving a hangover feeling to them, and then took coenzyme QlO after alcohol ingestion in divided doses over 2 hrs at intervals of 30 min. A survey was performed the next day.
  • the alcohol-induced hangover symptoms were graded on a scale of zero to ten, in which a score of 0 indicates a state in which no hangover is present, and a score of 10 indicates a severe hangover state.
  • the non-administration group ingested a placebo, wheat flour mixed with 1% beta-carotene.
  • coenzyme QlO was found to relieve hangover symptoms in dosages of 10 mg or greater. In particular, flushing and vomiting were greatly alleviated.
  • the maximal dosage of coenzyme QlO may not be limited, but a dosage of 20 g is preferred because it could eliminate most of the hangover symptoms. A dosage of 50 mg to 1 g is more preferred.
  • the other supplements along with the coenzyme QlO included the following: 1 g of squalene, 1000 IU of vitamin E, 2 g of silk peptides, 3 g of gurume, which indicate low molecular weight molecules extracted from a fermented concentrate of fruits and vegetables, 500 mg of aspirin, 500 mg of acetaminophen, 5 g of Hovenia dulcis Thunb extract, 5 g of Alnus japonica extract, and 5 g of Pueraria Root extract.
  • a placebo group was allowed to drink jasmine tea, which was turned dark by mixing caramel therein.
  • coenzyme QlO coenzyme QlO
  • total dosage 600 mg
  • Soju was ingested in amounts of 108 ml initially, 72 ml after 30 min, 90 ml after 45 min, and 90 ml after 1 hr. Thereafter, the faces of the subjects were observed for 3 hrs .
  • Coenzyme QlO was also found to inhibit flushing when taken after alcohol flushing had occurred. In this case, flushing was eliminated more than 30 min after coenzyme QlO intake, or was reduced to half its level compared to the case in which coenzyme QlO was not taken. Of course, these results were dependent on the amount of alcohol ingested and the dosage of coenzyme QlO.
  • coenzyme QlO is able to remarkably eliminate hangover symptoms when taken before, during or after alcohol consumption, or the next day hangover symptoms occur.
  • coenzyme QlO may be used as a means of eliminating or alleviating alcohol-related disorders, thereby greatly reducing the social side effects of alcohol.

Abstract

Disclosed is a pharmaceutical composition for eliminating and alleviating alcohol -related disorders. The pharmaceutical composition for eliminating and alleviating alcohol -related disorders including hangover symptoms or flushing comprises coenzyme Q10, which removes reactive oxygen species considered to be a cause of hangovers, as an effective ingredient. Also disclosed is a treatment method of alleviating alcohol-related disorders by taking the pharmaceutical composition before, during, after, or the day after alcohol consumption. Further disclosed is a functional food supplemented with the pharmaceutical composition, the food being taken as a side dish. The practical use of the pharmaceutical composition may greatly reduce the social side effects of alcohol consumption.

Description

[DESCRIPTION]
[invention Title]
COMPOSITION COMPRISING COENZYME QlO AS EFFECTIVE INGREDIENT
[Technical Field]
The present invention relates to a composition comprising coenzyme QlO as an effective ingredient. More particularly, the present invention relates to a pharmaceutical composition for eliminating and alleviating alcohol-related disorders comprising coenzyme QlO as an effective ingredient, a method of administering the composition, and a functional food using the composition.
[Background Art]
Efforts to find substances reducing blood concentrations of alcohol and acetaldehyde have been made so far mainly in order to develop substances for eliminating or alleviating alcohol-related disorders. This is because the exact mechanism of hangovers is still not fully understood.
Acetaldehyde is the major metabolite of alcohol, which is highly reactive and toxic. Since such acetaldehyde acts directly on the nervous system, resulting in the onset of various side effects, it is known to be responsible for most hangover symptoms (Sherif, S., Wahlstrom, G., Oreland, L.
Alcohol. Clin. Exp. Res. 17 (6) :1313-1318, 1993). However, hangover symptoms occur even 20 hours after alcohol consumption, at which time alcohol and acetaldehyde have been almost completely removed from the blood. Also, disulfiram, which is an aldehyde dehydrogenase inhibitor used in the treatment of alcohol-dependent patients and which accumulates acetaldehyde in the body, creating great discomfort in people who drink alcohol while taking the drug, aggravates symptoms caused by alcohol consumption, such as flushing and vomiting, but these symptoms do not represent all hangover symptoms. That is, hangovers are not caused only by acetaldehyde. Acetaldehyde has nevertheless been recognized as a major substance causing hangovers so that a lot of effort has been focused on the identification of substances inducing the rapid breakdown of alcohol and consequent acetaldehyde buildup in the body.
In addition to acetaldehyde, other toxic molecules are generated during alcohol metabolism, such toxic molecules being highly reactive oxygen-containing compounds known as "reactive oxygen species". The reactive oxygen species, which appear after alcohol consumption, release arachidonic acid from cells and induce cyclooxygenase-2 (hereinafter, referred to simply as "COX-2"), which is an enzyme synthesizing prostaglandins (hereinafter, referred to simply as "PG") , resulting in the synthesis of prostaglandin E2 (PGE2) , causing pain. Thus, hangover symptoms are present even when acetaldehyde is not present in the body.
People suffer from effects after drinking alcohol collectively known as a "hangover" . The main hangover symptoms are dizziness, headaches, and stomachaches (stomach irritation) , and other symptoms include fatigue, irritability, nausea, diarrhea, thirst, sleep disturbance, and chills
(Cephalagia, 3(1), 31-36 (1983)). During or immediately after alcohol consumption, flushing or vomiting as alcohol-related disorders may occur. In particular, flushing was found in the present invention to appear due to reactive oxygen species.
Coenzyme QlO, which is a strong antioxidant, is known as Ubiquinone, and also as coenzyme Q, helping the activity of some enzymes. Also, this substance is a benzoquinone derivative having a CH3O group at positions 2 and 3, and is distributed ubiquitously in biological systems and contained in a large amount in the mitochondria of cells. Coenzyme QlO acts to accept electrons from flavin enzymes and non-heme-iron proteins and to transfer them to cytochrome b. The present inventors found that reactive oxygen species generated during the breakdown of alcohol and acetaldehyde induce COX-2 expression at a high level, which in turn produces PGE2, leading to hangover symptoms accompanied by pain. Also, based on the fact that when a lot of heat is generated during alcohol breakdown, accompanied by the production of a number of reactive oxygen species in the cellular mitochondria, the present inventors considered coenzyme QlO, which displays a strong antioxidant activity in the cytosol while reducing the leakage of electrons by acting on the mitochondrial electron transport chain, to be excellent in eliminating hangover symptoms .
In this regard, the present inventors made many efforts to develop a method of treating alcohol-related disorders caused by alcohol consumption. As a result, a pharmaceutical composition/ comprising coenzyme QlO, removing reactive oxygen species leading to PGE2 production, as a major ingredient in order to inhibit the production of PGE2, known as a cause of hangover symptoms, and optionally another antioxidant, a substance reducing acetaldehyde concentrations in the body, and a COX-2 inhibitor, eliminates or alleviates alcohol-related disorders, including hangover symptoms and flushing. The finding also includes the observ -:ion that when coenzyme QlO is taken in an effective amount of LO rag to 20 g before, during, after, or the day following alcohol consumption, it has excellent therapeutic effect s against alcohol-related disorders, thereby leading to the present invention.
[Disclosure] [Technical Problem]
Accordingly, the present invention aims to provide a pharmaceutical composition for eliminating and alleviating alcohol-related disorders comprising coenzyme QlO as an effective ingredient, a method of administering the composition, and a functional food using the composition.
[Technical Solution] In order to accomplish the above objects, the present invention provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders comprising coenzyme QlO as an effective ingredient.
The present invention also provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders comprising, in addition to coenzyme QlO, one or more selected from the group consist ing of squalene, vitamin E, peptides, gurume, which indicate low molecular weight molecules extracted from a fermented concentrate of fruits and vegetables, Hovenia dulcis T;L:nb extract, Alnus japonica extract, and Pueraria Root extrac.
The present invention fur er provides a pharmaceutical composition for eliminating ai><~> alleviating alcohol-related disorders comprising, in addition to coenzyme QlO, a cyclooxygenase-2 (COX-2) inhibitor, preferably one or more selected from the group consisting of non-steroidal antiinflammatory drugs (NSAIDs) , aspirin, acetaminophen, ibuprofen, naproxen, phenacetin, mefenamic acid and indomethacin, celecoxib, diclofenac, etodolac, fenoprofen, ketoprofen, ketoralac, oxaprozin, nabumetone, sulindac, tolmetin, and rofecoxib.
The present invention further provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders, comprising coenzyme QlO in an effective amount of 10 mg to 20 g, preferably 50 mg to 1 g, the composition being taken before, during, after, or the day after alcohol consumption. The present invention further provides a functional food comprising the pharmaceutical composition for eliminating and alleviating alcohol-related disorders, the food being taken as a side dish during alcohol consumption.
The present invention further provides a functional food comprising coenzyme QlO in an effective amount of 10 mg to 20 g, the food being taken as a side dish during alcohol consumption and preferably being taken before, during, after, or the day after alcohol consumption.
The present invention further provides a treatment method for eliminating and alleviating alcohol-related disorders including hangover symptoms and flushing, comprising taking the pharmaceutical composition comprising coenzyme QlO in an effective amount of 10 mg to 20 g before, during, after, or the day after alcohol consumption. Hereinafter, the present invention will be described in detail .
Although acetaldehyde has been considered as the major cause of alcohol-related disorders including hangover symptoms, the exact mechanism of such disorders is still unknown. Thus, many efforts to screen substances eliminating hangover symptoms have focused on the reduction of alcohol and acetaldehyde concentrations in the blood.
However, hangover symptoms mainly appear after acetaldehyde is decomposed, and at this time, a large amount of prostaglandin E2, known as a pain-producing substance, is generated. Since reactive oxygen species generated during the metabolism of ingested alcohol are able to induce prostaglandin
E2 production, they are deemed as the major cause of hangover symptoms .
In addition, lipid peroxides are produced when cells are dosed with alcohol or acetaldehyde. This is due to the generation of reactive oxygen species upon acetaldehyde decomposition (Olin, K.L., Cherr, G.N., Rifkin, E., Keen, CL. Toxicology, 17:110 (1-3) ; 1-8, 1996). The intracellular formation of reactive oxygen species may mediate, in addition to lipid peroxidation, COX-2 induction, resulting in the conversion of arachidonic acid into prostaglandin E2 (PGE2) , and the increased PGE2 levels may cause pain associated with hangovers.
The present invention provides the use of coenzyme QlO as a hangover-eliminating substance, based on the aforementioned hangover mechanism.
In detail, the present invention provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders, comprising coenzyme QlO as an effective ingredient.
The present invention also provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders comprising, in addition to coenzyme QlO, another antioxidant. Preferred antioxidants include squalene, vitamin E, and peptides, which may be used singly or in combination. More preferably, in addition to the antioxidants, the pharmaceutical composition may further include a substance which is known to be effective in alleviating hangover symptoms by lowering acetaldehyde concentrations in the body. Examples of such substances include gurume, Hovenia dulcis Thurib extract, Alnus japonica extract, and Pueraria Root extract, which may be used singly or in combination. The present invention further provides a pharmaceutical composition for eliminating and alleviating alcohol-related disorders further comprising an inhibitor against COX-2 induced by reactive oxygen species. Preferably, the COX-2 inhibitor is a non-steroidal anti-inflammatory drug (NSAID) . More preferred examples of COX-2 inhibitors, which may be used singly or in combination, include aspirin, acetaminophen, naproxen, ibuprofen, phenacetin, mefenamic acid and indomethacin, celecoxib, diclofenac, etodolac, fenoprofen, ketoprofen, ketoralac, oxaprozin, nabumetone, sulindac, tolmetin, and rofecoxib.
The pharmaceutical composition for eliminating and alleviating alcohol-related disorders according to the present invention comprises coenzyme QlO in an effective amount of 10 mg to 20 g, and preferably 50 mg to 1 g. The composition is preferably taken before, during, after, or the day after alcohol consumption.
The present invention further provides the use of coenzyme QlO in the removal of reactive oxygen species before and after alcohol consumption. The present invention further provides a treatment method for eliminating and alleviating alcohol-related disorders, comprising taking the coenzyme QlO.
In the method, coenzyme QlO is preferably taken along with another antioxidant, and is more preferably taken along with squalene, vitamin E, and peptides, which may be used singly or in combination. It is also preferable to take, in addition to the coenzyme QlO and antioxidant, substances known to be effective in alleviating hangover symptoms by lowering acetaldehyde concentrations in the body, that is, gurume, Hovenia dulcis Thunb extract, Alnus japonica extract and Pueraria Root extract, and the like, which may be used singly or in combination.
In addition to coenzyme QlO, antioxidants and substances lowering acetaldehyde concentrations in the body, it is also preferable to further include an inhibitor against COX-2 induced by reactive oxygen species. The COX-2 inhibitor is preferably a non-steroidal anti-inflammatory drug (NSAID) . More preferably, other COX-2 inhibitors, including aspirin, acetaminophen, naproxen, ibuprofen, phenacetin, mefenamic acid and indomethacin, celecoxib, diclofenac, etodolac, fenoprofen, ketoprofen, ketoralac, oxaprozin, nabumetone, sulindac, tolmetin, and rofecoxib, are used singly or in combination. The COX-2 inhibitors are more preferably taken during or before and after alcohol consumption, rather than being taken the day after alcohol consumption, at the time that hangover symptoms occur.
In addition to coenzyme QlO, antioxidants, substances lowering acetaldehyde concentrations in the body and inhibitors against COX-2 induced by reactive oxygen species, it is also preferable to further take a supplement, such as chitosan, vitamin complexes comprising vitamin Bl, B2, C, etc., or the like.
In addition, in the treatment method of eliminating and alleviating alcohol-related disorders according to the present invention, the coenzyme QlO is preferably taken before, during, after, or the day after alcohol consumption in a form contained in a pharmaceutical composition in an effective amount of 10 mg to 20 g.
The present invention further provides a functional food supplemented with the pharmaceutical composition for eliminating and alleviating alcohol-related disorders, the food being used as a side dish upon alcohol consumption.
The pharmaceutical composition for eliminating and alleviating alcohol-related disorders according to the present invention may be used independently or as a drug additive along with a pharmaceutically acceptable carrier or excipient. Examples of carriers to be included in the pharmaceutical composition of the present invention are sufficiently known in the art, and may include thickeners, high fiber additives, capsulating agents, and lipids.
The pharmaceutical composition for eliminating and alleviating alcohol-related disorders according to the present invention may be administered by varying the dosage depending on the severity of the illness, the patient's age, sex, physical state, weight and diet, duration and mode of administration, rates of excretion of active agents, and the like.
The coenzyme QlO contained in the pharmaceutical composition of the present invention may be administered in a dosage of 0.1 mg to 0.2 g per kg of body weight via oral or parenteral routes.
[Description of Drawings]
FIGS. 1 and 2 are graphs showing that coenzyme QlO according to the present invention has an effect of inhibiting the production of lipid peroxides.
FIG. 3 is a graph showing the changes in plasma prostaglandin E2 levels upon administration of alcohol alone.
FIG. 4 is a graph showing the changes in plasma prostaglandin E2 levels upon administration of alcohol plus coenzyme QlO according to the present invention.
FIGS. 5 and 6 are photographs showing that coenzyme QlO according to the present invention has the effect of inhibiting flushing upon alcohol consumption.
FIGS. 7 and 8 are photographs showing that coenzyme QlO according to the present invention has the effect of inhibiting flushing upon alcohol consumption.
[Best Mode for Carrying Out the Invention]
A better understanding of the present invention may be obtained through the following examples which are set forth to illustrate, but are not to be construed as the limit of the present invention.
EXAMPLE 1 : Measurement of in vivo lipid peroxide levels after coenzyme QlO administration
In order to determine whether coenzyme QlO has an effect of inhibiting reactive oxygen species, ten rats weighing 450 g were divided into two groups : one group was dosed only with 3 ml of 50% ethanol, and another group was dosed with 3 ml of 50% ethanol and 0.08 g of coenzyme QlO dissolved in the ethanol.
Blood samples were collected at given time points, and lipid peroxidation was assessed by thiobarbuturic acid reaction
(Yagi, K. Biochem. Med. 15: 212-216, 1976). Blood alcohol concentrations were measured using headspace gas chromatography (J. Anal. Toxicol., 4(l):43-45, 1980). ■
The results are given in FIGS. 1 and 2. FIG. 1 shows the plasma levels of lipid peroxides (LPO) , wherein an open square indicates ethanol administration, and an open circle indicates ethanol plus coenzyme QlO administration. FIG. 2 shows blood alcohol concentrations, wherein an open square indicates ethanol administration, and an open circle indicates ethanol plus coenzyme QlO administration. As shown in FIGS. 1 and 2, when alcohol was administered along with coenzyme QlO, alcohol was rapidly decomposed, and the production of lipid peroxides decreased, compared to the administration of ethanol alone. These results indicate that the administration of coenzyme QlO along with alcohol was very effective in the removal of reactive oxygen species in the body.
EXAMPLE 2: Evaluation of the changes in blood PGE2 levels upon coenzyme QlO administration
Blood PGE2 levels were evaluated after alcohol ingestion, as follows. Rats weighing about 300 g were fasted for 12 hrs, and 3 g/kg of alcohol was then administered orally to the fasted rats. Blood samples were collected from the tail vein of rats at given time points, and blood PGE2 levels were determined using a commercially available kit for PGE2 measurement . Blood levels of alcohol and acetaldehyde were measured according to the same procedure as in Example 1.
The results are given FIG. 3. In FIG. 3, an open circle indicates blood PGE2 concentrations, an open triangle indicates blood alcohol concentrations, and an open square indicates blood acetaldehyde concentrations . As shown in FIG. 3 , PGE2 levels started to increase immediately after alcohol ingestion, and the elevated PGE2 levels were maintained even after 8 hrs, in which alcohol was not detected in the blood. It is clear from these results why hangover symptoms remain even 20 hrs after alcohol consumption.
In addition, coenzyme QlO was administered at a dosage of 1 g/kg. One third of the dosage was administered 1 hr before alcohol administration, and the remaining amount was administered in the form of being dissolved in alcohol. The results are given in FIG. 4. As shown in FIG. 4, the coenzyme QlO administration was found to reduce blood PGE2 levels compared to the administration of alcohol alone, indicating that coenzyme QlO greatly inhibited PGE2 production. Also, the blood levels of alcohol and acetaldehyde were slightly lower than those shown in FIG. 3, indicating that the ingested coenzyme QlO also quickly reduced the blood levels of alcohol and acetaldehyde.
EXAMPLE 3 : Evaluation of the inhibitory effects of coenzyme QlO on hangover symptoms
In order to investigate the changes in hangover symptoms according to coenzyme QlO, hangover symptoms were evaluated in sixteen college students who experienced a hangover feeling every time they ingested a Korean traditional distilled alcohol liquor, "Soju", five times or more (amount of alcohol ingested: 80-120 ml). The subjects ingested approximately l±0.5 bottles of Soju, giving a hangover feeling to them, and then took coenzyme QlO after alcohol ingestion in divided doses over 2 hrs at intervals of 30 min. A survey was performed the next day. The alcohol-induced hangover symptoms were graded on a scale of zero to ten, in which a score of 0 indicates a state in which no hangover is present, and a score of 10 indicates a severe hangover state. The non-administration group ingested a placebo, wheat flour mixed with 1% beta-carotene.
The results are given in Table 1, below. Individuals receiving coenzyme QlO developed almost no headaches, stomachaches, nausea and dizziness, showing high statistical significance. Flushing and heat in the face were also determined immediately after alcohol ingestion. As described in Table 1, flushing and heat in the face were greatly suppressed, showing high statistical significance. Furthermore, coenzyme QlO was found to have excellent effects of reducing other alcohol-induced symptoms, including fatigue, irritability, diarrhea, thirst, sleep disturbance, and chills. In this test, the administration of coenzyme QlO resulted in the incidence of almost no alcohol-related disorders. This was considered to result from the excellent ability of coenzyme QlO to scavenge reactive oxygen species . [TABLE 1]
The hangover-eliminating effects of coenzyme QlO upon alcohol ingestion
Figure imgf000016_0001
p<0.05 compared to the control
EXAMPLE 4 : Evaluation of the hangover-eliminating effects of coenzyme QlO over time
In order to investigate the hangover-eliminating effects of coenzyme QlO over time, two individuals who experienced a hangover feeling every time they ingested just a half bottle
(180 ml) of Soju (alcohol concentration: 22%) were divided into
Group 1 and Group 2, and two other individuals who experienced a hangover feeling when ingesting one bottle (360 ml) of Soju were divided into Group 1 and Group 2. Coenzyme QlO (500 mg) was administered before, during and after alcohol consumption, and the day hangover symptoms occurred. The degree of the hangovers was examined the next day. This test was performed repeatedly at intervals of two weeks. The same placebo as in Example 3 was administered, and a survey was also performed according to the scale described in Example 3. The survey asked questions not for each of the hangover symptoms as described in Table 1 but for the overall degree of hangover, and the subjects answered such questions. The results are given in Table 2, below. As shown in Table 2, when coenz- e QlO was administered before, during and after alcohol >nsumption, almost no hangover symptoms were observed the n <t day. When coenzyme QlO was administered the next day t ■ subjects experienced reduction of hangovers, nausea, fatigυ , and the like by more than 70% 30 min after administration, h ϊdaches reduced only by about 40%. These results indicate that coenzyme QlO is effective when taken at the time of a ' cohol consumption, and also largely relieves a hangover even .tfhen taken at the time the hangover occurs.
[TABLE 2] The hangover-eliminating effects of coenzyme QlO over time
Administration time The degree of hangover (score)
Non-administration of coenzyme QlO 8
Before alcohol ingestion
During alcohol ingestion
Immediately after alcohol ingestion The time hangovers occur
EXAMPLE 5 : Evaluation of the hangovei eliminating effects of coenzyme QlO according to administration concentrations
In order to investigate the hang • ^er-eliminating effects of coenzyme QlO according to adminit- ration concentrations, four individuals who are poor drinkers, ^or example, developing flushing even when ingesting one smalj. glass (45 ml) of Soju
(alcohol concentration: 22%) , were d~' ided into two groups, each group consisting of two persons. he subjects were dosed with coenzyme QlO in amounts of 5 mg, "" ? mg, 20 mg, 50 mg, 100 mg, I g and 20 g, and the degree of hangover was examined. In detail, in each test, coenzyme QlO was not administered, or was administered in an amount of 5 mg. After two weeks, coenzyme QlO was administered in amounts of 10 mg and 20 mg. Two weeks thereafter, coenzyme QlO was administered in amounts of 50 mg and 100 mg. Two weeks thereafter, coenzyme QlO was administered in amounts of 1 g and 20 g. According to the same procedure as in Examples 3 and 4, a placebo was administered, and a survey was performed. The amount of wheat flour was adjusted to maintain the total administration amount at constant levels .
As shown in Table 3, below, coenzyme QlO was found to relieve hangover symptoms in dosages of 10 mg or greater. In particular, flushing and vomiting were greatly alleviated. The maximal dosage of coenzyme QlO may not be limited, but a dosage of 20 g is preferred because it could eliminate most of the hangover symptoms. A dosage of 50 mg to 1 g is more preferred.
[TABLE 3] The hangover-eliminating effects of coenzyme QlO according to administration concentrations
Figure imgf000018_0001
EXAMPLE 6 : Evaluation of the hangover-eliminating effects of coenzyme QlO according to combinatic \ thereof with other supplements
In order to investigate the hango /er-eliminating effects of coenzyme QlO when used in combination with other supplements, each of ten poor drinkers was allowed to drink a half bottle of Soju and coenzyme QlO along with other supplements for 2 hrs. A hangover test was carried out according to the same procedure as in Example 4. 200 mg of coenzyme QlO was ingested. The other supplements along with the coenzyme QlO included the following: 1 g of squalene, 1000 IU of vitamin E, 2 g of silk peptides, 3 g of gurume, which indicate low molecular weight molecules extracted from a fermented concentrate of fruits and vegetables, 500 mg of aspirin, 500 mg of acetaminophen, 5 g of Hovenia dulcis Thunb extract, 5 g of Alnus japonica extract, and 5 g of Pueraria Root extract. A placebo group was allowed to drink jasmine tea, which was turned dark by mixing caramel therein.
The results are given in Table 4, below. As shown in Table 4, the combination of coenzyme QlO with other supplements resulted in almost no incidence of hangover symptoms, such as dizziness, headaches, stomachaches (stomach irritation) and fatigue, and also resulted in almost no occurrence of flushing or nausea, which may occur during or aft^r alcohol consumption. Antioxidants or substances lowering acetaldehyde concentrations were found to be effective on flushing or nausea, and aspirin or acetaminophen were found not to be ■ -ffective in inhibiting these symptoms, but displayed excellent effects of eliminating hangover symptoms the day after ale hoi consumption. Of course, these supplements exhibited good effects when used in combination. Also, the administration of chitosan and vitamin B and C complexes (16 mg vitamin Bl, 10 mg vitamin B2, and 300 mg vitamin C) resulted in good effects.
[TABLE 4]
The hangover-eliminating effects of coenzyme QlO according to combination with other supplements
Figure imgf000020_0001
EXAMPLE 7 : Evaluation of the hangover-eliminating effects of coenzyme QlO taken in the form of a side dish
In order to investigate the hangover-eliminating effects of coenzyme QlO in the form of being contained in a side-dish food, a hangover test was performed according to the same procedure as in Example 4. In this test, coenzyme QlO was prepared in the form of capsules and mixed with a snack, and the mixture was provided as a side dish. A non-administration group was allowed to ingest a placebo, wheat flour mixed with 1% beta-carotene . As a result, the same results as shown in Table 2 were obtained. When coenzyme QlO was taken in the form of a side dish, it exhibited the same effects of eliminating or alleviating alcohol-related disorders. EXAMPLE 8 : Evaluation of the alleviation of flushing of coenzyme QlO when taken before alcohol consumption
In order to investigate the ability of coenzyme QlO to alleviate flushing, two individuals who always developed flushing ingested one glass (50 ml) of Soju (alcohol concentration: 22%) were selected. The subjects were allowed to drink Soju in amounts of 108 ml initially, 72 ml after 30 min, 90 ml after 45 min, and 90 ml after 1 hr. The subjects started to develop flushing about 15 min after the initial alcohol consumption. The results are given in FIGS. 5 and 7. The face of each subject was photographed before and 2 hrs after alcohol consumption. The photographs show that the face of both subjects turned severely red.
In addition, after one week, according to the same method, the subjects were allowed to ingest commercially available coenzyme QlO (Co-QlO; total dosage: 600 mg) while drinking alcohol. The coenzyme QlO was taken in amounts of 200 mg 1 hr before alcohol ingestion, 200 mg 30 min before alcohol ingestion, 100 mg upon initial alcohol ingestion, and 100 mg 30 min after alcohol ingestion. According to the same procedure as in the above control test, Soju was ingested in amounts of 108 ml initially, 72 ml after 30 min, 90 ml after 45 min, and 90 ml after 1 hr. Thereafter, the faces of the subjects were observed for 3 hrs . No flushing occurred in the face of the subjects who ingested alcohol along with coenzyme QlO for the observation period of 3 hrs. The subjects had only a feeling of heat in their face. The face of each subject was photographed 1 hr after alcohol ingestion. The results are given in FIGS. 5 and 7. As shown in FIGS. 6 and 8, respectively, no flushing appeared when coenzyme QlO was taken before or during alcohol consumption.
Coenzyme QlO was also found to inhibit flushing when taken after alcohol flushing had occurred. In this case, flushing was eliminated more than 30 min after coenzyme QlO intake, or was reduced to half its level compared to the case in which coenzyme QlO was not taken. Of course, these results were dependent on the amount of alcohol ingested and the dosage of coenzyme QlO.
EXAMPLE 9 : Evaluation of the ability of coenzyme QlO to alleviate flushing when taken during and after alcohol consumption
The flushing-alleviating effect of coenzyme QlO was further examined, as follows . Four individuals who developed flushing upon alcohol consumption were allowed to drink 180 ml of Soju (alcohol concentration: 22%) over one hour. In this case, as expected, the faces of the subjects turned red. At this time, two of the subjects were dosed with coenzyme QlO. The flushing was relieved after 30 min, and almost eliminated after one hour. In contrast, the flushing remained in the faces of the two remaining subjects not taking coenzyme QlO.
[industrial Applicability]
As described hereinbefore, coenzyme QlO is able to remarkably eliminate hangover symptoms when taken before, during or after alcohol consumption, or the next day hangover symptoms occur. According to the present invention, coenzyme QlO may be used as a means of eliminating or alleviating alcohol-related disorders, thereby greatly reducing the social side effects of alcohol.

Claims

[CLAIMS]
[Claim l]
A pharmaceutical composition for eliminating and alleviating alcohol-related disorders, comprising coenzyme QlO as an effective ingredient.
[Claim 2]
The pharmaceutical composition for eliminating and alleviating alcohol-related disorders according to claim 1, further comprising one or more selected from the group consisting of squalene, vitamin E, peptides, gurume, Hovenia dulcis Thunb extract, Alnus japonica extract, and Pueraria Root extract .
[Claim 3]
The pharmaceutical composition for eliminating and alleviating alcohol-related disorders according to claim 1 or 2, further comprising one or more cyclooxygenase-2 inhibitors selected from the group consisting of non-steroidal antiinflammatory drugs (NSAIDs) , aspirin, acetaminophen, ibuprofen, naproxen, phenacetin, mefenamic acid and indomethacin, celecoxib, diclofenac, etodolac, fenoprofen, ketoprofen, ketoralac, oxaprozin, nabumetone, sulindac, tolmetin, and rofecoxib.
[Claim 4]
The pharmaceutical composition for eliminating and alleviating alcohol-related disorders according to any one of claims 1 to 3, wherein the coenzyme QlO is present in an effective amount of 10 mg to 20 g, the composition being taken before, during, after, or the day after alcohol consumption.
[Claim 5]
A functional food comprising the pharmaceutical composition for eliminating and alleviating alcohol-related disorders according to claim 1, the food being taken as a side dish during alcohol consumption.
[Claim 6]
The functional food according to claim 5, wherein the coenzyme QlO is present in an effective amount of 10 mg to 20 g, the food being taken before, during, after, or the day after alcohol consumption.
PCT/KR2006/000605 2005-02-26 2006-02-22 Composition comprising coenzyme q10 as effective ingredient WO2006091010A1 (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998007417A1 (en) * 1996-08-16 1998-02-26 Kaneka Corporation Pharmaceutical composition comprising coenzyme q¿10?
US20030113307A1 (en) * 2001-12-12 2003-06-19 Selzer Jonathan A. Co-enzyme Q10 dietary supplement

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998007417A1 (en) * 1996-08-16 1998-02-26 Kaneka Corporation Pharmaceutical composition comprising coenzyme q¿10?
US20030113307A1 (en) * 2001-12-12 2003-06-19 Selzer Jonathan A. Co-enzyme Q10 dietary supplement

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Title
BEYER R.E.: "Inhibition by coenzyme Q of ethanol-and carbon tetrachloride-stimulated lipid peroxidation in vivo and catalyzed by microsomal and mitochondrial systems", FRE RADIC. BIOL. MED., vol. 5, no. 5-6, 1988, pages 297 - 303, XP025577794, DOI: doi:10.1016/0891-5849(88)90100-1 *
HOBARA N. ET AL.: "Quinone derivatives lower blood and liver acetaldehyde but not ethanol concentrations following ethanol loading to rats", PHARMACOLOGY, vol. 37, no. 4, 1988, pages 264 - 267, XP000675950 *
JUNQUEIRA ET AL.: "Content of liver and brain ubiquinol-9 and ubiquinol-10 after chronic ethanol intake in rats subjected to two levels of dietary alpha-tocopherol", FREE RADIC. RES., vol. 33, no. 3, September 2000 (2000-09-01), pages 313 - 319 *
MANSOURI A. ET AL.: "Acute ethanol administration oxidatively damages and depletes mitochondrial DNA in mouse liver, brain, heart, and skeletal muscles: protective effects of antioxidants", J. PHARM. EXP. THER., vol. 298, no. 2, 2001, pages 737 - 743 *

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