WO2008002019A1

WO2008002019A1 - Anti-hangover composition

Info

Publication number: WO2008002019A1
Application number: PCT/KR2007/002571
Authority: WO
Inventors: Il Hwan Cho; Chul Kyu Lee; Jang Sik Shin; Byung Soo Kim
Original assignee: Il Hwan Cho; Chul Kyu Lee; Jang Sik Shin; Byung Soo Kim
Priority date: 2006-06-28
Filing date: 2007-05-28
Publication date: 2008-01-03
Also published as: KR100626167B1

Abstract

Disclosed herein is an anti-hangover composition. The anti-hangover composition for preventing and treating hangovers comprises a freeze-dried earthworm powder or an earthworm-extracted supernatant, both of which contain lumbrokinase as an active ingredient, wherein the earthworm-extracted supernatant is prepared by wet-grinding living earthworms and centrifuging the grinded earthworms and the freeze-dried earthworm powder is prepared by filtering the supernatant and freeze-drying the filtrate. The anti-hangover composition is efficacious for preventing and relieving hangovers, and protecting gastrointestines against alcohol.

Description

[invention Title] ANTI-HANGOVER COMPOSITION

[Technical Field] The present invention relates to an anti-hangover composition. More specifically, the present invention relates to an anti-hangover composition effective for preventing and treating hangovers, comprising a freeze-dried earthworm powder or an earthworm-extracted supernatant, both of which contain lumbrokinase as an active ingredient, wherein the earthworm-extracted supernatant is prepared by wet-grinding living earthworms and centrifuging the grinded earthworms, and the freeze-dried earthworm powder is obtained by filtering the supernatant and freeze-drying the filtrate.

[Background Art]

As the prior arts related to the present invention, there may be mentioned Korean Patent Publication Nos . 1999- 0046190 (Reference 1; Patent Application No. 1998-0040476) and 2001-0097318 (Reference 2; Patent Application No. 2000- 0021296). The Reference 1 discloses an anti-hangover beverage containing Hovenia dulcis Thunb and a method for preparing the same. The Reference 2 discloses a functional beverage containing an arrowroot extract and a method for preparing the same.

A dried earthworm powder has been used for antihyperlipemic, antidiabetic, blood pressure-controlling and antithrombosis preparations, which is based on medical efficacy thereof recorded in Oriental Medicine Literatures

(Shinnongbonchogyeong, etc).

The afore-mentioned Hovenia dulcis Thunb and the arrowroot extract are efficacious for treating hangovers, but are insufficient to obtain a desired effect. For this reason, the prior arts have problems in that these ingredients must be used in a larger amount. Accordingly, there was a need for a novel anti-hangovor composition. The present inventors have conducted this research, taking into consideration the facts that dried earthworm powders contains lumbrokinase, one of the proteases, as an active ingredient, and that stomach damage caused by alcohol is closely associated with the corresponding protease activated receptor (PAR) reacted with a protease.

[Disclosure] [Technical Problem]

The present invention has been made to solve the foregoing problems of the prior art and it is one aspect of the present invention to provide an anti-hangover composition for preventing and treating hangover by containment of : a freeze-dried earthworm powder, which is prepared by wet- grinding living earthworms, centrifuging the grinded earthworms, filtering the collected supernatant and freeze- drying the filtrate and contains lumbrokinase as an active ingredient; or the supernatant.

[Technical Solution] In accordance with an aspect of the present invention for achieving the above aspect, there is provided an anti- hangover composition efficacious for preventing and treating hangovers, comprising a freeze-dried earthworm powder or an earthworm-extracted supernatant, both of which contain lumbrokinase as an active ingredient, wherein the earthworm- extracted supernatant is prepared by wet-grinding living earthworms and centrifuging the grinded earthworms, and freeze-dried earthworm powder is prepared by filtering the supernatant and freeze-drying the filtrate. The anti-hangover composition is effective for preventing and treating hangovers, and furthermore, for protecting the stomach and intestines from alcohol.

[Advantageous Effects] The anti-hangover composition of the present invention is efficacious for preventing and relieving hangovers, and protecting gastrointestines against alcohol.

[Description of Drawings]

The above and other aspects, 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: FIGs. 1 to 3 are photographs showing the gastrointestines of a control group according to one embodiment of the present invention;

FIGs. 4 to 6 are photographs showing the gastrointestines of a comparative group according to another embodiment of the present invention;

FIGs 7 to 9 are photographs showing the gastrointestines of Preparation Example 4 according to another embodiment of the present invention;

FIG. 10 is a photograph showing the gastrointestines of Preparation Example 1 according to another embodiment of the present invention;

FIG. 11 is a photograph showing the gastrointestines of Preparation Example 2 according to another embodiment of the present invention; FIG. 12 is a photograph showing the gastrointestines of Preparation Example 3 according to another embodiment of the present invention;

FIG. 13 is a photograph showing the gastrointestines of Preparation Example 5 according to another embodiment of the present invention; and

FIG. 14 is a photograph showing the gastrointestines of Preparation Example 6 according to yet another embodiment of the present invention.

[Best Mode]

The present invention will now be described with reference to the accompanying drawings in greater detail. The anti-hangover composition according to the present invention comprises a freeze-dried earthworm powder or a supernatant extracted from earthworms (hereinafter, referred to simply as "earthworm supernatant") .

Preferably, the anti-hangover composition further comprises at least one of a Hovenia dulcis Thunb extract and an arrowroot extract.

Preferably, the freeze-dried earthworm powder or earthworm supernatant, the Hovenia dulcis Thunb extract, and the arrowroot extract are used in a weight ratio of 1 : 1-20 : 1-20. Preferably, the anti-hangover composition further comprises at least one selected from taurin, a pear juice, an apple juice, high fructose, honey, citric acid, malic acid, sodium citrate, sodium benzoate, sorbitol, vitamin Bi, vitamin B₂, vitamin B₆, vitamin C, royal jelly and a lemon essence, and the selected ingredient is added in an amount of 0.1-325 fold, with respect to the weight of the freeze-dried earthworm powder or the earthworm supernatant. Preferably, the anti-hangover composition further comprises distilled water in an amount of 100-2,000 folds, with respect to the weight of the freeze-dried earthworm powder or the earthworm supernatant .

Lumbrokinase contained in the freeze-dried earthworm powder or the earthworm supernatant is known to be a serine-based protease, is stable against heat or pH, and exhibits a specific activity for fibrin, one of constituent components of thrombus. Lumbrokinase is believed to exert stable efficacy in the stomach, despite its protein-like biochemical properties. Korea is one of the highest alcohol consuming nations, in particular, is ranked fourth in all nations, in terms of consumption level of strong liquor e.g. soju or whiskey. The high alcohol consumption is attributed to a general increase in liquor consumption level, however, is proven to be greatly affected by an increase in liquor consumption of females and young people. The total alcohol consumption level per person is 6.7 L, which reaches the top twenty or so. But, the consumption level in high-alcoholicity distilled liquors per person is 4.5 L, which reaches the top fourth. Incidence of hangovers, side effects caused by an excessive intake of strong liquors is on the rise. About 10% of the alcohol absorbed in the body via drinking is discharged through respiration or urination to the outside and the remaining alcohol is mostly metabolized in the gastric mucous membrane and the liver. About 90 to 95% of the metabolized alcohol is oxidized and decomposed in the liver. Alcohol is oxidized through three metabolic pathways. Specifically, the alcohol is decomposed into CO₂ and H₂O through the following three pathways: the action of alcohol dehydrogenase (ADH) present in the gastric mucous membrane and the liver; the action of a microsomal ethanol oxidizing system (MEOS) present in the endoplasmic reticulum; and the action of catalase in the peroxisome. An adequate amount of alcohol consumed is naturally oxidized by the afore-mentioned metabolism. On the other hand, excessive alcohol intake upsets the balance between metabolic systems, making it impossible to maintain intracellular homeostasis, thereby causing diseases such as liver diseases, gastritis, pancreatitis, hypertension, paralysis, esophagitis, diabetes and heart diseases (Korean Institute for Health and Social Affairs). A hangover is defined as a phenomenon in which unpleasant feelings or symptoms (e.g. headache, stomachache or lack of concentration) after awaking from sleep following heavy drunkenness last for one to two days. The causes of this phenomenon are not clearly ascertained to late. It was reported by Leiber CC, Gastroenterol 1994; 106, 1085-1105 that the hangover is attributed to acetaldehyde, the primary metabolic product of alcohol, rather than inherent toxicity of alcohol. That is, excessively consumed alcohol cannot be rapidly decomposed into acetic acid and be metabolized, and exists as acetaldehyde in the body, thus causing damage to hepatocytes and brain cells and inducing symptoms such as sweat, rapid pulse, skin flushing, nausea and vomiting. Several remedies effective for hangovers are known, for example, there may be mentioned: an alcohol ingredient is removed from the body; when sensing feelings of vomiting, attempts are made to thoroughly vomit; vitamin B₁ or moisture is taken to promote the decomposition of alcohol; and foods with diuretic effects such as coffee, teas, fruit juices are taken. A great deal of protease activated receptors (PARs) present in the stomach and intestines are reported to contribute to protection of the stomach and intestines. Accordingly, the present inventors ascertained through repeated activity tests freeze-dried earthworm powders and earthworm supernatant are efficacious for preventing and treating hangovers, taking into account the fact that hangovers can be prevented or treated by suitably controlling these receptors, thereby completing the present invention.

[Mode for Invention]

The present invention will be better understood from the following examples. These examples are not to be construed as limiting the scope of the invention.

EXAMPLES

Example 1; Preparation of freeze-dried earthworm powder

Of earthworms belonging to the Phylum Annelida, Subclass Oligochaeta, red worms (Lumbricus rubellus), tiger worms (Eisenia fetida), large reddish worms (Lumbricus terrestris), or red tiger worms (Eisenia andrei) were purchased from a farm breeding earthworms for feeds and fishing bait. 10 Kg of raw worms were thoroughly washed with distilled water to remove foreign materials and subjected to wet-grinding. The resulting worms were centrifuged at 3,000 *g for 30 min to obtain a supernatant (8.5 kg). The supernatant was filtered through diatomaceous silica to separate water-insoluble materials therefrom. The resilting residue was freeze-dried to prepare a freeze-dried earthworm powder. The weight of the freeze-dried earthworm powder obtained from the raw earthworms (10 Kg) was 1.2 Kg and a titer of a casein digestion was 870 units /g.

Example 2 : Preparation of anti-hangovor beverage containing freeze-dried earthworm powder

There is no traditional Korean medical literature in which Hovenia dulcis Thunb is mentioned. However, several traditional Chinese medical literatures (Bonchokangmok, Bonchoseupyou, Dangboncho, Sunghaebang, etc.) teach that Hovenia dulcis Thunb is the best hangover medicine. The Sunghaebang reads as "alcohol is severely toxic. Thus, insufficient removal of alcoholic toxicity prevailed in the body following alcohol drinking causes considerably unbearable suffering. If you wish to treat alcoholism resulting from excessive alcohol intakes, decoct one nyang (ca. 35 gram) of Hovenia dulcis Thunb stem slices in a bowl of water until the water reduces to half, remove remnants from the decoction and drink the resulting Hovenia dulcis Thunb extract. Thereafter, treatment efficacy can be got as rapid as lightning". In addition, Donguibogam reads as "An arrowroot is mild (also called "cool" as an Oriental medical term), tastes sweet and has no toxicity. Arrowroot is efficacious for treating headache caused by common cold, rendering sweat pores to open and relieving hangovers".

Accordingly, the Hovenia dulcis Thunb and arrowroot extracts known to effectively relieve hangovers were added as reinforcing agents of the freeze-dried earthworm powder. That is, according to the composition as set forth in Table 1, the freeze-dried earthworm powder prepared in Example 1 as a main ingredient and the Hovenia dulcis Thunb and arrowroot extracts obtained by a common extraction method as reinforcing agents were fed into a mixing tank. The temperature was elevated to 50 ^°C and the mixture was completely dissolved with thoroughly stirring. After completion of the mixing, the reaction mixture was subjected to low-temperature centrifugation at 3,000*g for 10 min and filtration through a filter to remove precipitate or flotage therefrom. Taurin, a pear juice, high fructose and other ingredients were added according to the composition as set forth in Table 1 to prepare anti-hangovor beverages of Preparation Examples 1 to 6.

Table 1: Preparation Examples of anti-hangover beverages from freeze-dried earthworm powder

Example 3; Effects of gastrointestinal protection in alcohol-injury model

5 week-old SD white male rats weighting 200 to 250 g were used as subjects. The rats were fasted for 24 hours or more and bred in a wire cage to prevent the rats from ingesting their excrements during the fasting. Anti- hangover beverages of Preparation Examples 1 to 6 prepared in Example 2 were administered to the rats at 30 min prior to alcohol-induced gastrointestinal injury. The gastrointestinal injury was induced by oral-administrating 1 mL of anhydrous alcohol to each subject.

At one hour following the alcohol administration, the rats were anesthetized with ketamine, blood was collected from abdominal aortic aneurysm and the liver and stomach were enucleated. After allowed to stand at a low temperature for 2 hours, the collected blood was centrifuged for 10 min at 700*g to separate serum therefrom. A 10-fold amount of 2% trichloroacetic acid was added to the serum and centrifuged to obtain analytical serum. About 3 mL of kit reagent for alcohol assay was added to lOμJt of the analytical serum and the mixture was then thoroughly stirred. The mixture was allowed to react at 37 ^°C for 5 min. The absorbance at 340 nm of the reaction mixture was measured for the fractions, in contrast with an alcohol standard solution, to assay alcohol concentrations in blood. The liver and intestines thus enucleated were divided into mitochondria, microsome and cytosol fractions according to a method of Choi et al . (2000) and alcohol and aldehyde dehydrogenase activities were evaluated. Alcohol dehydrogenase (ADH) activity was assessed by calculating the amount of alcohol converted to acetaldehyde per one minute. More specifically, 1.3 ml of 50 mM sodium pyrophosphate buffer (pH 8.8) was put into each test tube, 0.1 ml of 95% ethanol, 1.5 ml of 10 mM β-NAD and 0.1 ml of the cytosol fraction were then added thereto and homogeneously stirred. Immediately, the absorbance of the mixture was measured at 340 nm for 5 min with a spectrophotometer. Meanwhile, acetaldehyde dehydrogenase (ALDH) activity was assessed by calculating the amount of acetaldehyde oxidized to acetic acid per one minute. More specifically, 2.32 ml of distilled water, 0.3 ml of 1. OM Tris-HCl buffer (pH 8.0), 0.1 ml of 20 mM β-NAD, 0.05 ml of a 100 mM acetaldehyde solution, 0.1 ml of 3M KCl, and 0.03 ml of IM 2- mercaptoethanol were added to each test tube and 0.1 mL of the mitochondria fraction was then added thereto, following by homogeneously stirring. Immediately, the absorbance of the mixture was measured at 340 nm for 5 min with a spectrophotometer. The mole number of acetaldehyde decomposed per minute was calculated to evaluate the aldehyde dehydrogenase (ALDH) activity.

The pylorus of the stomach enucleated was ligated, 3mL of a 2% formalin solution was injected through the cardiac orifice and the specimen was fixed for 10 min. After completion of the fixation, the greater curvature of the stomach was excised and washed with physiological saline. The resulting greater curvature was thoroughly stretched, fixed on a fixing plate and taken as a photograph. The photographs were shown in FIGs. 1 to 9. Specifically, FIGs. 1 to 3 are photographs showing the gastrointestines of a control group; FIGs. 4 to 6 are photographs showing the gastrointestines of a comparative group; FIGs. 7 to 9 are photographs showing the gastrointestines according to Preparation Example 4; FIG. 10 is a photograph showing the gastrointestines according to Preparation Example 1; FIG. 11 is a photograph showing the gastrointestines according to Preparation Example 2; FIG. 12 is a photograph showing the gastrointestines according to Preparation Example 3; FIG. 13 is a photograph showing the gastrointestines according to Preparation Example 5; and FIG. 14 is a photograph showing the gastrointestines according to Preparation Example 6. The area of injured gastrointestine in the photographs was measured with a bio-imaging analyzer system. The results were shown in Table 2. The control group was an experimental group to which only distilled water was administered. The comparative group was an experimental group to which "C" product available from CJ Corporation, having the highest market share in the field of hangover beverages was administered. All of the freeze-dried earthworm powder-containing beverages prepared in Preparation Examples exhibited a decrease in alcohol concentration in blood, an increase in alcohol and aldehyde dehydrogenase activities and statistically significant inhibition against gastrointestinal injury. Table 2: Anti-hangover effects in animal subjects

^ All values indicate average ± standard error.

*: statistical significance at 95% confidence level, in contrast with control group

**: statistical significance at 99% confidence level, in contrast with control group

Example 4; Tests for hangover prevention and relief effects in human subjects 151 adult males who frequently drink and suffer from serious hangovers participated in these tests for ascertaining hangover prevention and relief efficacies of the freeze-dried earthworm powder. First, questionnaire research was conducted to ascertain the level of usual hangovers . The anti-hangover beverage of Preparation Example 4 prepared in Example 2 was allowed to administer to the subjects at one hour prior to drinking. In the following day, questionnaire research was conducted to ascertain the level of hangover relief.

Table 3 shows stomachache of subjects before drug administration. 89% of the subjects said that they had suffered from hangover symptoms such as stomachache after drinking. On the other hand, the remaining 11% subjects said that they had felt no hangover symptom. The anti- hangover beverage containing the freeze-dried earthworm powder as an active ingredient was administered to the subjects. In the following day, the subjects participated in questionnaire survey associated with hangover symptoms. The results were shown in Tables 4 and 5. Similar to the results shown in Table 3, 86% of the respondents said the beverage is slightly or more efficacious, in particular, 36% of them said the beverage has a significant efficacy. On the other hand, respondents who consented to "ineffectiveness" were only 14% in total. 92% of the subjects said that they got positive effects against other hangovers e.g. headache and vomiting.

Table 3: Stomachache level of subjects after drinking (before drug administration)

Table 4: Relief level in stomachache of subjects after drinking (after drug administration)

Table 5: Relief level in other hangover symptoms (e.g. headache and vomiting) of subjects after drinking (after drug administration)

Example 5 ; Preparation of supernatant extracted from earthworm

Of earthworms belonging to the Phylum Annelida, Subclass Oligochaeta, red worms (Lumbricus rubellus), tiger worms (Eisenia fetida), large reddish worms

(Lumbricus terrestris ) , or red tiger worms (Eisenia andrei) were purchased from a farm breeding earthworms for feeds and fishing bait. 10 Kg of raw worms were thoroughly washed with distilled water to remove foreign materials and subjected to wet-grinding. The resulting worms were centrifuged at 3,000*g for 30 min to obtain a supernatant.

The water-insoluble materials were filtered off through diatomaceous silica to prepare a desired earthworm-extracted supernatant (8.5 kg).

The weight of the earthworm-extracted supernatant was about seven times that of the freeze-dried earthworm powder.

Example 6; Preparation of earthworm supernatant- containing anti-hangover beverage

An anti-hangover beverage was prepared in the same manner as in Example 2 except that about 7-fold weight of the earthworm-extracted supernatant was used instead of the freeze-dried earthworm powder. Example 7 ; Effects of gastrointestinal protection in alcohol-injury model

The tests were conducted in the same manner as in Example 3 except that the anti-hangover beverage prepared in Example 6 was used instead of the anti-hangover beverage prepared in Example 2.

Example 8; Tests for hangover prevention and relief effects in human subjects

The tests were conducted in the same manner as in

Example 4 except that the anti-hangover beverage of

Preparation Example 4 prepared in Example 6 was used instead of the anti-hangover beverage prepared in preparation example 4 of Example 2.

The results obtained from Examples 6 to 8 were the same as those of Examples 2 to 4.

[industrial Applicability] As apparent from the foregoing, the anti-hangover composition of the present invention is efficacious for preventing and relieving hangovers, and furthermore, protecting gastrointestines against alcohol, thus being industrially applicable.

Claims

[CLAIMS]

[Claim l] An anti-hangover composition comprising a freeze-dried earthworm powder or an earthworm-extracted supernatant .

[Claim 2]

The anti-hangover composition according to claim 1, further comprising at least one of a Hovenia dulcis Thunb extract and an arrowroot extract.

[Claim 3]

The anti-hangover composition according to claim 2, wherein the freeze-dried earthworm powder or earthworm supernatant, the Hovenia dulcis Thunb extract, and the arrowroot extract are used in a weight ratio of 1 : 1-20 : 1-20.

[Claim 4] The anti-hangover composition according to claim 3, wherein the composition further comprises at least one selected from taurin, a pear juice, an apple juice, high fructose, honey, citric acid, malic acid, sodium citrate, sodium benzoate, sorbitol, vitamin Bi, vitamin B₂, vitamin B₆, vitamin C, royal jelly and a lemon essence, and the weight of the selected ingredient is 0.1 to 325 folds of the weight of the freeze-dried earthworm powder or the earthworm supernatant.

[Claim 5]

The anti-hangover composition according to any one of claims 1 to 4, wherein the composition further comprises distilled water in an amount of 100 to 2- ,000 folds, with respect to the weight of the freeze-dried earthworm powder or the earthworm supernatant.