WO2005049052A1

WO2005049052A1 - Composition for prevention and relief of alcoholic hangover, and alcoholic liquors containing magnesium compound and/or magnesium salt

Info

Publication number: WO2005049052A1
Application number: PCT/KR2004/003015
Authority: WO
Inventors: Yong-Geun Kwak; Hyung Sub Kang; Jae-Soon Eun; June-No So; In-Choul Park
Original assignee: WON GENESIS Corp
Current assignee: WON GENESIS Corp
Priority date: 2003-11-20
Filing date: 2004-11-19
Publication date: 2005-06-02
Anticipated expiration: 2006-05-20
Also published as: KR20050049416A

Abstract

The present invention relates to a composition for preventing and relieving hangover, and functional liquor containing one or more ingredients selected form the group consisting of magnesium compounds and magnesium salts. The above-mentioned composition for preventing and relieving hangover can activates alcohol and acetaldehyde metabolism. And protect hepatocytes and gastric parietal cell, thus minimizing side effects of alcohol. And the functional liquor minimizes hangover when taken.

Description

COMPOSITION FOR PREVENTION AND RELIEF OF ALCOHOLIC HANGOVER, AND ALCOHOLIC LIQUORS CONTAINING MAGNESIUM COMPOUND AND/OR MAGNESIUM SALT

Technical Field The present invention relates to a composition for preventing and relieving hangovers, and functional liquor containing one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts.

Background Art Alcohols have been used by humans throughout recorded time, and have beneficial aspects such as facilitating harmony and relationships, relieving stress, promoting sleep and promoting metabolism. But continuous excessive drinking causes fatal liver diseases and an excessive amount of alcohol is not sufficiently absorbed and degraded in vivo, thus resulting in headaches and gastrointestinal irritation. Excessive alcohol intake is known not only to cause gastrointestinal disorders (Mach, T. Protective effect of alkalies on ethyl alcohol-damaged gastric mucosa. Folia Med. Cracov. 30(3-4): 93-101,1989), but also to promote excretion of magnesium in vivo thus decreasing a magnesium concentration in blood leading to various diseases including cardiovascular diseases (Chakraborti et al. Protective role of magnesium in cardiovascular diseases: a review. Mol Cell Biochem. Sep; 238 (1-2): 163-79, 2002), kidney diseases (Vamvakas et al. Alcohol abuse: potential role in electrolyte disturbances and kidney diseases. Clin Nephrol. Apr: 49(4) 205-13, 1998) and nervous system-^* diseases (Thomson. Mechanisms of vitamin deficiency in chronic alcohol misusers and the development of the Wernicke-Korsakoff syndrome. Alcohol. 2000). The main ingredient of liquors is ethanol. After ingested, ethanol is metabolized and converted to acetaldehyde by alcohol dehydrogenase mainly in the liver, and as metabolism progresses further, the resulting acetaldehyde is degraded into CO₂ and H₂O by acetaldehyde dehydrogenase. Usually, moderate drinking causes these enzymes to function smoothly, reducing side effects. But heavy drinking causes acetaldehyde to accumulate, bringing about side effects such as vomiting and headache. Some habitual drinkers worry about side effects of drinking and take a variety of beverages and medicines to avoid such side effects, but it is not sufficient to essentially relieve hangovers. A large number of hangover-cure-preparations developed hitherto have mainly focused on decreasing only blood alcohol concentration and thus there remains a need in the art for developing a preparation capable of effectively alleviating and relieving hangover due to acetaldehyde that is the main cause of side effects when ingesting a large amount of alcohol. Further, various kinds of functional liquors have been developed in which a variety of extracts, herbal medicines and additives having various characteristics were mixed, but they still do not have noticeable effects on hangovers, headaches and electrolyte loss. For examples of such products, alcohol concentration of Soju (a traditional Korean distilled liquor) is lowered for gentle and mild drinking, or Soju was mixed with green tea known as having a certain degree of efficacy to relieve hangovers. Such a product has been gaining popularity among commercially available Soju liquors because habitual drinkers prefer liquors that cause a reduced hangover and are mild for drinking. But it has room to further improve problems associated with hangover, headache and electrolyte loss. Disclosure of the Invention Technical Problem Therefore, the present inventors found that magnesium compounds and/or magnesium salts not only simultaneously decrease acetaldehyde and blood alcohol concentrations, but also have protective effects for hepatocyte and gastroparietal cell, and thereby made the present invention based on this fact.

Technical Solution The present invention relates to a composition for preventing and relieving hangover, and a functional alcohol containing one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts.

The representative examples of magnesium compounds in according to the present invention are magnesium oxide, magnesium hydroxide and the like. In addition, the representative examples of magnesium salts in according to the present invention are magnesium chloride, magnesium sulfate, magnesium citrate, magnesium lactate, magnesium stearate and magnesium gluconate and the like. In particular, magnesium oxide and magnesium gluconate are more preferable. The term "a composition for preventing and relieving hangover" as used herein encompasses pharmaceutical compositions, food products, beverages and food additives for such use, i.e., preventing and relieving hangover. The composition for preventing and relieving hangover in accordance with the present invention may be administered, usually 1 to 3 times per day, 1 to 2400 mg each time, preferably 10 to 1000 mg each time, based on the magnesium content from the magnesium compounds and/or magnesium salts contained in the composition. The composition for preventing and relieving hangover in accordance with the present invention may contain one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts in an amount of 0.01 to 95% by weight based on the magnesium content. The present inventors have found through experiments that before or after alcohol intake, ingestion of an appropriate amount of one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts activates enzymes such as alcohol dehydrogenase and acetaldehyde dehydrogenase involved in alcohol metabolism in vivo (Thomasson et al. Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism. Behavior Genetics. 23(2): 131-136, 1993), and has supplementary effects for loss of magnesium in blood due to alcohol, thereby exhibiting excellent effects for preventing and relieving hangover. Among compositions for preventing and relieving hangover in accordance with the present invention, a pharmaceutical preparation for this purpose can be formulated in various forms that contain pharmaceutically acceptable carriers, excipients and/or additives. That is, the composition according to the present invention can be formulated in the form of a conventional formulation, for example oral formulations such as tablets, capsules, solutions and powders, and parenteral formulations such as injectable preparations and transdermal preparations. Among compositions for preventing and relieving hangover in accordance with the present invention, a food composition for this purpose is applicable to various food products. For example, mention may be made of beverages, teas, soups and broths, and health supplement and the like. The composition for preventing and relieving hangover in accordance with the present invention may also be used in the form of a food additive for such use. For example, the composition of the present invention may be prepared in the form of an additive, adding to various food products. As another aspect of the present invention, a functional liquor composition refers to a composition containing one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts in an amount of 0.01 to 100 g/L, and preferably 0.1 to 50 g/L in the liquor, based on the magnesium content. The magnesium content may be suitably regulated according to alcohol concentration of the liquor. The above-mentioned liquor includes general liquors such as beer, Soju, whisky and the like, and preferably refers to liquors of which the alcohol concentration is 4 to 50%(v/v).

Brief Explanation of Drawings The above and other objects, features and other advantages of the present invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which: Fig. 1 shows blood alcohol concentration profile over time after a mixture of magnesium gluconate and alcohol was administered orally to rats; Fig. 2 shows acetaldehyde concentration in blood profile over time after a mixture of magnesium gluconate and alcohol was administered orally to rats; Fig. 3 shows blood concentration profile over time after the mixture of magnesium gluconate and alcohol was administered orally to human beings; Fig. 4 is photographs of stomachs observed with the naked-eye after distilled water (control), magnesium gluconate, ethanol, and ethanol+magnesium gluconate for 7 days were administered to male rats in control and experimental groups, followed by autopsy; Fig. 5 is a bar graph showing feed intake of male rats administered with distilled water (control), magnesium gluconate, ethanol, and ethanol+magnesium gluconate; Fig. 6 is a bar graph showing drinking water intake of male rats administered with distilled water (control), magnesium gluconate, ethanol, and ethanol+magnesium gluconate; and Fig. 7 is a bar graph showing changes in body weight of male rats administered with distilled water (control), magnesium gluconate, ethanol, and ethanol+magnesium gluconate.

Best Mode for Carrying Out the Invention Now, the present invention will be described in more detail with reference to the following Examples and Experimental Examples. These examples are provided only for illustrating the present invention and should not be construed as limiting the scope and sprit of the present invention.

EXAMPLES

Example 1 : Preparation of solution for preventing and relieving hangover Single syrup was mixed in 500 mg of magnesium gluconate and 0.3 ml of diluted hydrochloric acid to be 100 ml so as to prepare a solution for preventing and relieving hangover. Example 2 : Preparation of solution for preventing and relieving hangover Single syrup was mixed in 500 mg of magnesium oxide and 0.3 ml of dilute hydrochloric acid to be 100 ml so as to prepare a solution for preventing and relieving hangover.

Example 3 : Preparation of other preparations A pill, granule, tablet and capsule each comprising 700 mg of magnesium gluconate were prepared according to conventional methods.

Example 4 : Preparation of liquor containing magnesium salts 60 g of magnesium gluconate was dissolved in 1,000 ml of sterile distilled water and then the solution was mixed with 40% ethanol in the ratio of 1 : 1 to prepare 20%(v/v) ethanol.

Experimental Example 1 : Effects of magnesium gluconate on alcohol and acetaldehyde concentrations in blood of rats

(1) Experimental Method Six male Sprague-Dawley rats, weighing 200 to 250 g, were assigned to each group and used for experiments. Experimental animal groups consisted of the control group in which alcohol were administered to rats, and the group in which alcohol with magnesium gluconate were administered to rats. The rats in the alcohol-administered group were orally administered with 40% ethanol (2g/kg). Whereas, the rats of alcohol with magnesium gluconate-administered group were administered orally with a mixture of 2g/kg of 40% ethanol and 10 mg/kg (based on the magnesium content) of magnesium gluconate. Two hours after administration, animals were suffocated with CO gas, bloods were collected and blood concentrations of alcohol and acetaldehyde were measured. Blood alcohol concentration was measured by gas chromatography and acetaldehyde concentration was measured by HPLC. Measurement of acetaldehyde concentration in blood was performed as follows. One ml of 0.01 M dinitrophenylhydrazine (DNPH) that had been dissolved in 3.6 M HCl, was added to 1 ml of blood. The solution was mixed well at room temperature for 30 min, added 20 ml of pentane and mixed. Then, the resulting mixture was centrifuged at 3,500 rpm for 20 min. The pentane layer thus obtained was washed with 10 ml of distilled water three times, centrifuged again. A small amount of anhydrous sodium sulfate (Na₂SO₄ anhydrous) was added to and mixed with the pentane layer. The layer was centrifuged to separate the pentane layer, which was then concentrated by an evaporator. The concentrate thus obtained was analyzed quantitatively by HPLC using a mixed solvent of 0.5 ml acetonitrile and distilled water. Novapak C18 (Waters Co.) was used as the column for HPLC, and a mixture of acetonitrile and distilled water (in the ratio of 1:1) was used as the eluent. The retention time of acetaldehyde was 4.95 min.

(2) Experimental Results As shown in Fig. 1, there was no significant difference between the blood alcohol concentration of the magnesium gluconate-administered group and that of alcohol-administered control group, up to 1 hour after administration. But the blood alcohol concentration of the magnesium gluconate-administered group was remarkably decreased 2 hours after administration. In addition, as you can be seen from Fig. 2, the same results were also observed for acetaldehyde concentration in blood. Experimental Example 2: Effects of magnesium gluconate on blood alcohol concentration of the human body

(1) Experimental Method Six healthy men without any particular gastrointestinal disease (average age: 25.6+2.5) participated in this study in a double-blind fashion. That is, the experiments were performed such that neither the subjects nor the experimental field supervisor knew which samples were given to the subjects. Further, in order to reduce differences between individuals, the subjects in the alcohol- administered control group and the other subjects in the alcohol with magnesium gluconate-administered group were tested again with the reversed treatment 2 weeks after the first experiment. The men in control group drank 700 ml of 21% alcohol per person for 1 hour and the men in the alcohol with magnesium gluconate-administered group drank 700 ml of 21% alcohol containing 1.4 g of magnesium gluconate dissolved therein per person. Blood alcohol concentration was measured according to the same method as Experimental Experiment 1.

(2) Experimental Results As shown in Fig. 3, blood alcohol concentration of the men in the group in the alcohol with magnesium gluconate-administered group started to significantly decrease 2 hour after administration.

Experimental Example 3: Effects of administration of ethanol with magnesium gluconate on rats (1) Experimental Method Each of test samples was administered orally to male rats (weighing about 250 g) with the interval of 12 hours, twice a day in an amount of 1 ml each time, tor 7 days. One ml of distilled water, the magnesium gluconate solution (30 g of the magnesium gluconate in 1,000 ml of distilled water), 20% ethanol, or the liquor prepared in Example 4 was administered orally to each of rats in control group, in the magnesium gluconate-administered group, in the ethanol-administered group, or in the ethanol with magnesium gluconate-administered group, respectively.

(2) Experimental Results

i) Effects on morphology of stomach When observed the external appearance of stomach of rats after the administration of test samples for 7 days, there was vasodilation on the outer wall of the stomach of rats in the magnesium gluconate-administered group whereas there was the atrophy in outer wall of stomach of rats in the alcohol-administered group. However, such atrophy observed in the alcohol-administered group, wasn't observed in outer wall of stomach of rats the stomachs of rats in the ethanol with magnesium gluconate- administered group. Upon observing the inside of the stomach after dissection, there was no significant difference between the magnesium gluconate-administered group and control group. And demarcated ulcers and bleeding were observed in the alcohol- administered group, whereas such ulcers and bleedings were not observed in the ethanol with magnesium gluconate-administered group (Fig. 4). ii) Effects on drinking water intake, feed intake and changes in body weight The feed intakes of rats in control group and the magnesium gluconate- administered group were found to be 20.7+3.5 g/day and 21.1+3.2 g/day, respectively. No difference was observed between the two groups. But, that of rats in the ethanol- administered group was remarkably decreased to 10.4+2.3 g/day, and that of rats in the ethanol with magnesium gluconate-administered group was 19.3+3.3 g/day, representing significant increase as compared to the ethanol-administered group (Fig. 5). Meanwhile, the drinking water intakes of rats in control group and the magnesium gluconate-administered group were found to be 56.6+6.8 ml and 56.6+8.0 ml, respectively. No difference was observed between the groups. But, that of rats in the ethanol-administered group was remarkably decreased to 26.6+2.4 ml compared to the control group. And that of rats in the ethanol with magnesium gluconate-administered group was significant increased to 48.3+2.0 ml compared to the ethanol-administered group (Fig. 6). Body weights of rats in control group and the magnesium gluconate- administered group were found to be 16.0+2.1% and 18.3+3.5%, respectively. No difference was observed between the groups. But, body weight of rats in the ethanol- administered group was remarkably decreased -to -9.3+2.1% compared to the control group. Body weight of rats in the ethanol with magnesium gluconate-administered group was significantly increased to 9.4+2.1% compared to the ethanol-administered group (Fig. 7).

iii) Effects on changes in biochemical markers in blood As for biochemical markers in blood such as glucose, total cholesterol, blood urea nitrogen (BUN), total bilirubin, glutamate-oxalate-transaminase (GOT) and glutamate-pyruvate-transaminase (GPT) determined for each experimental group, there was no significant difference between the magnesium gluconate-administered group and control group. But, GOT and GPT markers were increased in the ethanol-administered group, compared to the control group, and decreased in the ethanol+magnesium gluconate-administered group as compared to the ethanol-administered group (Table 1).

Table 1

* represents significant difference between the ethanol-administered group and control group. * P < 0.05, ** P < 0.01, represents significant difference between the ethanol+magnesium gluconate- administered group and ethanol-administered group, P < 0.05 , ^$* P < 0.01

Taken together, significant decrease in feed intake, decrease in drinking water intake, loss of body weight, and increase in GOT and GPT markers among biochemical markers in blood, usually caused by the administration of ethanol, were disappeared by the administration of a mixture of magnesium gluconate and ethanol.

Industrial Applicability The present invention provides a composition for preventing and relieving hangover which is capable of promoting the metabolism of alcohol and acetaldehyde and protecting hepatocytes and gastric parietal cells, thus minimizing side effects of alcohol, and a functional liquor minimizing hangover when taken.

Claims

1. A composition for preventing and relieving hangover containing one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts.

2. The composition as set forth in claim 1, wherein the composition contains one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts in an amount of 0.01 to 95% by weight based on the magnesium content.

3. The composition as set forth in claim 1, wherein one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts contained in the composition is administered 1 to 3 times per day, 1 to 2400 mg each time, based on the magnesium content.

4. The composition as set forth in claim 1, wherein the magnesium compound is selected from the group consisting of magnesium oxide and magnesium hydroxide, and the magnesium salt is selected from the group consisting of magnesium chloride, magnesium sulfate, magnesium citrate, magnesium lactate, magnesium stearate and magnesium gluconate.

5. The composition as set forth in claim 1, wherein the composition is prepared in the form of a pharmaceutical preparation, food product, beverage or food additive.

6. The composition as set forth in claim 1, wherein the ingredient selected from the group consisting of magnesium compounds and magnesium salts is magnesium gluconate.

7. A functional liquor comprising one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts.

8. The functional liquor as set forth in claim 7, wherein the liquor contains one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts in an amount of 0.01 to 100 g/L, based on the magnesium content.

9. The functional liquor as set forth in claim 7, wherein the magnesium compound is selected from the group consisting of magnesium oxide and magnesium hydroxide, and the magnesium salt is selected from the group consisting of magnesium chloride, magnesium sulfate, magnesium citrate, magnesium lactate, magnesium stearate and magnesium gluconate.

10. The functional liquor as set forth in claim 7, wherein the ingredient selected from the group consisting of magnesium compounds and magnesium salts is magnesium gluconate.

11. The functional liquor as set forth in claim 7, wherein the alcohol concentration of the liquor is 4 to 50%(v/v).

12. A method for preventing and relieving hangover, comprising administering an effective amount of a composition as set forth in Claim 1 to a human.

13. Use for preventing and relieving hangover of a composition as set forth in claim 1.