WO2008088174A1

WO2008088174A1 - The composition comprising swellfish extracts using protease, and a manufacturing method thereof

Info

Publication number: WO2008088174A1
Application number: PCT/KR2008/000296
Authority: WO
Inventors: Sang Gil Lee
Original assignee: Individual
Current assignee: Individual
Priority date: 2007-01-19
Filing date: 2008-01-17
Publication date: 2008-07-24
Anticipated expiration: 2009-07-19

Abstract

The present invention relates to a swellfish extract prepared by using protease, a manufacturing method thereof and a composition for treating hangover which comprises the swellfish extract as an active ingredient. Particularly, the swellfish extract of the present invention prepared by using protease has more active ingredients than other swellfish extracts prepared by hot-water and alcohol. The swellfish extract containing artichoke (Cynara scolymus) has significant synergy effect for treating hangover, compared with the individual swellfish extract or artichoke extract, so that it can be effectively used as a composition for treating hangover.

Description

[DESCRIPTION]

[invention Title]

THE COMPOSITION COMPRISING SWELLFISH EXTRACTS USING PROTEASE, AND A MANUFACTURING METHOD THEREOF

[Technical Field]

The present invention relates to a swellfish extract prepared by using protease, a manufacturing method thereof and a composition for treating hangover which comprises the swellfish extract as an active ingredient.

[Background Art]

It is generally known that hangover observed in human body after drinking is more likely induced by acetaldehyde, the first metabolite of alcohol than by the toxicity of alcohol itself.

[0 ] [0 ]

CH₃CH₂OH » CH₃CH=O + CH₃COOH

(EtOH) I ♦ ((AAcceettaallddeehhyyddee)) f f (Acetacid)

EtOH dehydrogenase Acetaldehyde dehydrogenase

That is, alcohol is decomposed by alcohol dehydrogenases to be converted into acetaldehyde which is decomposed to acetic acid. Acetaldehyde, the high concentrated active compound, can induce sweating, rapid pulse, skin flushing, nausea and vomiting. Thus, most researchers thought that acetaldehyde, the metabolite of alcohol, would be the reason of hangover.

A proper amount of alcohol does not cause malfunctions or bad phenomenon in human body owing to the oxidation system working smoothly. However, alcohol overdose destroys the balance of metabolic system, resulting in fail in maintaining homeostasis in cells. The most easily affected organ by alcohol overdose is the liver. That is, excessive alcohol drinking causes liver function disorder in the long term, for example fatty liver, liver cirrhosis, etc, and causes headache, heavy headness, lack of concentration, heartburn and indigestion in the short term.

To treat hangover, foods prepared with dried pollack, bean sprouts and swellfish as a main ingredient have been widely used. In particular, swellfish has been a favorite for habitual drinkers since it was considered as a food efficient especially for hangover in China.

Swellfish contains plenty of proteins along with various amino acids, minerals and vitamins and activates alcohol dehydrogenase in human body to enhance liver detoxication and is effective in preventing alcoholism and in treating hangover. In addition, swellfish has the effect of reducing cholesterol and lowering high blood pressure, resulting in prevention of adult disease. So, it is the favored food for dietary treatment for such patients before or after surgery or with diabetes or kidney disease. It is described in ^ΛDongeuebogam' that swellfish warms up the body, invigorates, reduces edema, is effective in treatment of waist and leg pain, has treatment effect on hemorrhoid, and has insecticidal effect.

As a hangover treating food, artichoke (scientific name: Cynara scolymus) has been used in Europe. Artichoke has been known to have hangover treating effect in addition to the preventive and treatment effect on indigestion and adult disease including coronary artery disease and high blood sugar. European countries and Japan have been in the center of the study on artichoke, especially concerning various biological functions of artichoke and its components .

Artichoke is native to Mediterranean and is a perennial plant in shape of a thistle flower, only a few times bigger than that. Artichoke grows to 2 meters in height and spreads wide to 1 meter in square. Flower bud of artichoke is soft and tastes plain and is nutritious, particularly it has plenty of proteins, vitamin A, vitamin C, calcium, iron, phosphate, saccharides and inulin. Particularly, it contains saccharides functioning like insulin in patients with diabetes, making it as an important medicine. Cynarin component contained in leaves or roots accelerates bile secretion and is effective in the treatment of impaired liver function and gastrointestinal disorder and in regulation of blood cholesterol, so that Lt has been used as a therapeutic agent for arteriosclerosis in Europe. It is also used for the treatment of liver disease and kidney disease, especially effective when protein level in urine is high, owing to its diuretic effect and blood cleaning effect. The various functions of artichoke are resulted from the strong anti-oxidation activity of its extract. This strong anti-oxidation activity, particularly, enhances the functions of promoting bile secretion and protecting liver cells. In addition, artichoke has been proved to have a great lipid absorption inhibitory effect. Artichoke has been proved to be a safe material and classified as GRAS (generally recognized as safe) by FDA, USA.

Thus, the present inventors continued to study to develop a method for preparing a composition for treating hangover with improved health enhancing effect along with excellent hangover treating effect but without side effects. And as a result, the present inventors found out the fact that swellfish extract prepared by using protease had effective ingredients more than that prepared by hot water or alcohol extraction had. And further, the present inventors completed this invention by confirming that swellfish extract containing artichoke as an additional ingredient had superior hangover treating effect triggered by synergy effect, compared with each individual swellfish extract and artichoke extract.

[Disclosure] [Technical Problem] It is an object of the present invention to provide a swellfish extract prepared by using protease, a manufacturing method thereof and a composition for treating hangover which comprises the swellfish extract as an active ingredient .

[Technical Solution]

To achieve the above object, the present invention provides a manufacturing method of a swellfish extract using protease. The present invention also provides a swellfish extract prepared by the method of the above.

The present invention further provides a pharmaceutical composition for treating hangover which comprises the swellfish extract as an active ingredient. The present invention also provides a method for treating hangover comprising the step of administering pharmaceutically effective dose of the swellfish extract to a subject.

The present invention also provides a use of the swellfish extract for the production of the pharmaceutical composition for treating hangover.

The present invention also provides a health food for treating hangover which comprises the swellfish extract as an active ingredient. In addition, the present invention provides a use of the swellfish extract for the production of the health food for treating hangover.

[Advantageous Effect] The swellfish extract prepared by protease of the present invention includes more effective ingredients than the swellfish extract prepared by hot water or alcohol does. The swellfish extract additionally containing artichoke has better hangover treating effect than independent swellfish extract or artichoke, and has liver function enhancing effect. In addition, the swellfish extract of the present invention is a safe natural food without side effects, has excellent hangover treating effect and excellent health enhancing effect.

[Description of Drawings]

The application of the preferred embodiments of the present invention is best understood with reference to the accompanying drawings, wherein:

Fig. 1 is a graph illustrating the time dependent blood ethanol concentrations after treating the swellfish protease extract containing artichoke.

Fig. 2 is a graph illustrating the time dependent blood acetaldehyde concentrations after treating the swellfish protease extract containing artichoke.

[Best Mode]

Hereinafter, the present invention is described in detail.

In this invention, ^λhangover' indicates the general symptoms shown after alcohol drinking, for example headache, diarrhea, lack of appetite, nausea, vomiting, etc, which generally accompanies the decrease of recognition and locomotion, hematological and hormonal changes. In this invention, ^Λenzyme reaction product' indicates the swellfish extract containing active ingredients of swellfish which are extracted from swellfish flesh by using protease.

The present invention provides a manufacturing method of a swellfish extract comprising the following steps:

1) separating swellfish flesh from swellfish: 2) reacting the swellfish flesh of step 1) with enzyme: and

3) obtaining distillate by distillation with the enzyme reaction product of step 2).

In the above method, the swellfish of step 1) can be torafugu (Takifugu rubripes) or shirosabafugu (Lagocephalus wheeleri Abe) , which can be captured from the nature or by breeding. Swellfish is a deadly poisonous fish, so that it can be dangerous unless treated properly. So, only the cook qualified and specialized in swellfish cooking is allowed to cook it. Particularly poisonous intestines have to be eliminated together with head and skin. Only swellfish flesh is preferably used as a material for preparing the swellfish extract.

In the above method, the enzyme of step 2) is protease. In this invention, swellfish is not boiled or decocted. Instead, protease that is an enzyme to decompose proteins is used to decompose swellfish flesh to extract every effective ingredient of swellfish. That is, effective ingredients included in swellfish flesh are extracted by using protease as many as possible. To do so, swellfish flesh is put in a reactor equipped with temperature regulator, to which the same weight of water is added. Protease (enzyme content: 0.1-0.2%) is preferably added thereto, but the amounts of water and enzyme are not limited thereto. The preferable enzyme reaction temperature is approximately 25-50 ^°C and particularly 37 ^°C is more preferred because the reaction speed of protease is fastest at that temperature, but not always limited thereto. The preferably enzyme reaction time is approximately 12-36 hours, but not always limited thereto.

In the above method, the distillation of step 3) is preferably performed at 65-100^°C. If the temperature for distillation is higher than 100^°C, heat-denaturation of enzyme reaction product might be caused. Therefore, the temperature for distillation is preferably at low temperature which is lower than 100^°C. The distillation preferably continued until the volume of enzyme reaction product becomes 1/3-1/2, but not always limited thereto. In this invention, swellfish is not boiled or decocted but distilled. And, only distillate except the solid material remained after distillation is used. Thus, poisonous materials are automatically excluded and only effective ingredients of swellfish remain in swellfish concentrate. At this time, fish smell can also be eliminated.

Preferably, artichoke powder is additionally added to the swellfish extract obtained by the method above, followed by filtration and aging. The preferable content of artichoke powder in the swellfish extract is 2 ~ 8 q/t, but not always limited thereto. It is preferred to filter the swellfish extract 1 ~ 3 hours after the addition of artichoke powder using 1000 ~ 1400 mesh net. It is preferred to age the swellfish extract 5 - 20 hours at 40 ~ 60 ^°C, but not always limited thereto.

The present invention also provides a swellfish extract prepared by the method of the present invention.

The present invention further provides a pharmaceutical composition for treating hangover which comprises the swellfish extract as an active ingredient.

In this invention, the present inventors investigated through animal tests how differently the swellfish extract prepared by protease could reduce blood alcohol and acetaldehyde, compared with the swellfish extract prepared by hot-water or alcohol. Distilled water, swellfish protease extract, swellfish hot-water extract and swellfish ethanol extract were orally administered to rats respectively, then, alcohol was orally administered to the rats. Blood samples were taken every hour and ethanol and acetaldehyde concentrations in blood were measured by using a kit. As a result, the swellfish extracts exhibited no statistically significant reducing effect on blood alcohol but still could lower the blood alcohol, compared with the control. In the meantime, the swellfish extracts exhibited statistically significant reducing effect on blood acetaldehyde compared with the control. The swellfish protease extract was confirmed to have statistically significant reducing effect on both blood alcohol and acetaldehyde, compared with other swellfish extracts prepared by hot-water or ethanol. Therefore, the swellfish extract prepared by protease of the present invention was proved to have more effective ingredients for treating hangover than others. In this invention, the present inventors also investigated whether the sweLlfish protease extract additionally containing artichoke had better hangover treating effect than individual swellfish extract or artichoke extract. 15% diluted and undiluted solutions of each swellfish protease extract not containing artichoke, artichoke extract and swellfish protease extract containing artichoke were orally administered to rats, and then, alcohol was orally administered to the rats. Blood samples were taken every hour and ethanol and acetaldehyde concentrations in blood were measured by using a kit. As a result, the blood alcohol and blood acetaldehyde reducing effect of 15% diluted solution and 100% undiluted solution of swellfish extract containing artichoke was statistically significant, compared with that of the swellfish extract undiluted solution not containing artichoke or artichoke extract undiluted solution. Therefore, it was confirmed that the swellfish extract containing artichoke additionally had more excellent hangover treating effect than swellfish extract not containing artichoke or artichoke extract.

The present invention also provides a method for treating hangover comprising the step of administering pharmaceutically effective dose of the swellfish extract to a subject.

The pharmaceutical composition can include, in addition to swellfish extract, one or more effective ingredients having the same or similar function to swellfish extract.

The pharmaceutical composition of the present invention can be administered orally or parenterally and be used in general forms of pharmaceutical formulation. The composition of the present invention can be prepared for oral or parenteral administration by mixing with generally used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactant. Solid formulations for oral administration are tablets, pills, powders, granules and capsules. These solid formulations are prepared by mixing the pharmaceutical composition of the present invention with one or more suitable excipients such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, such lubricants as magnesium stearate and talc can be used. Liquid formulations for oral administrations are suspensions, solutions, emulsions and syrups, and the above-mentioned formulations can contain various excipients such as wetting agents, sweeteners, aromatics and preservatives in addition to generally used simple diluents such as water and liquid paraffin. Formulations for parenteral administration are sterilized aqueous solutions, water-insoluble excipients, suspensions, emulsions, lyophilized preparations and suppositories. Water insoluble excipients and suspensions can contain, in addition to the active compound or compounds, propylene glycol, polyethylene glycol, vegetable oil like olive oil, injectable ester like ethylolate, etc. Suppositories can contain, in addition to the active compound or compounds, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol, gelatin, etc. The therapeutic agent of the present invention can be administered by hypodermic injection, intravenous injection or intramuscular injection.

The present invention also provides a health food for treating hangover which comprises the swellfish extract as an active ingredient.

In addition, the present invention provides a use of the swellfish extract for the production of the health food for treating hangover.

The swellfish extract of the present invention can be used as a food additive. In that case, the swellfish extract can be added as it is or as mixed with other food components according to the conventional method. The mixing ratio of active ingredients can be regulated according to the purpose of use (prevention, health enhancement or treatment) . In general, to produce health food or beverages, the pharmaceutical composition of the present invention is added preferably by up to 15 weight part and more preferably by up to 10 weight part. However, if long term administration is required for health and hygiene or regulating health condition, the content can be lower than the above but higher content can be accepted as well since the swellfish extract has been proved to be very safe .

The food herein is not limited. For example, the swellfish extract can be added to meats, sausages, breads, chocolates, candies, snacks, cookies, pizza, ramyuns, flour products, gums, dairy products including ice cream, soups, beverages, tea, drinks, alcohol drinks and vitamin complex, etc, and in wide sense, almost every food applicable in the production of health food can be included.

The composition for health beverages of the present invention can additionally include various flavors or natural carbohydrates, etc, like other beverages. The natural carbohydrates above can be one of monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xilytole, sorbitol, and erythritol. Besides, natural sweetening agents such as thaumatin and stevia extract, and synthetic sweetening agents such as saccharin and aspartame can be included as a sweetening agent.

In addition to the ingredients mentioned above, the swellfish extract of the present invention can include in variety of nutrients, vitamins, minerals, flavors, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acid, protective colloidal viscosifiers, pH regulators, stabilizers, antiseptics, glycerin, alcohols, carbonators which used to be added to soda, etc. The swellfish extract of the present invention can also include natural fruit juice, fruit beverages and/or fruit flesh addable to vegetable beverages. All the mentioned ingredients can be added independently or together.

[Mode for Invention] Practical and presently preferred embodiments of the present invention are illustrative as shown in the following Examples.

However, it will be appreciated that those skilled in the art, on consideration of this disclosure, may make modifications and improvements within the spirit and scope of the present invention.

Example 1: Preparation of swellfish extract <!-!> Swellfish extract prepared by protease Approximately 5 kg of flesh was separated from cleaned torafugu (Takifugu rubripes) or shirosabafugu

(Lagocephalus wheeleri Abe) . Then, the swellfish flesh was put in a reactor, to which 5 t of purified water and 7 g of protease (subtilisin produced by Bacillus subtilis (titer: 16,000 u/g) were added. Temperature of the reactor was maintained at 37^°C for 24 hours, followed by enzyme reaction with stirring to prepare swellfish solution. Upon completion of the enzyme reaction, temperature of the reactor was adjusted to 97^°C. The swellfish solution was distilled for about 8 hours until the volume of the swellfish solution was down to 1/2 with stirring, during which the lid of the reactor was opened to release vapor. After distillation, the reactor was turned off and left until the temperature was lowered to room temperature. Swellfish extract (5 t) was obtained from the distillate.

<l-2> Swellfish extract containing artichoke

Artichoke powder sold on the market was added into the swellfish extract obtained in Example <1-1> by 0.2%. The mixture was put in a reactor and well mixed, followed by filtering with 1,000 mesh net. Temperature of the filtered swellfish extract was adjusted to 45-50^°C, followed by aging for 12 hours. As a result, 5 I of swellfish hot-water extract was obtained. <l-3> Swellfish hot-water extract

5 kg of the separated swellfish flesh was homogenized, which was put in a reactor. 5 I of purified water was added thereto, followed by hot-water extraction at 90 - 100^°C twice for 4 hours each. As a result, 5 I of swellfish hot-water extract was obtained.

<l-4> Swellfish ethanol aqueous solution extract

5 kg of the separated swellfish flesh was homogenized. The homogenized swellfish and 5 t of 95% ethanol aqueous solution were added in an extraction vessel, followed by reflux condensing (water temperature of water bath: 80^°C).

As a result, 5 i of swellfish ethanol extract was obtained.

<l-5> Artichoke extract

5 kg of dried artichoke was pulverized, to which 5 ( of purified water was added. The artichoke solution was heated at 90 - 100^°C for 2 hours, and then cooled down to room temperature, followed by filter pressing. The filtered solution was concentrated under reduced pressure, followed by hot-air drying. As a result, 5 i of artichoke extract was obtained.

Experimental Example 1: Hangover treating effect of swellfish protease extract 40 Sprague-Dawley rats were grouped by 10, followed by animal tests examining hangover treating effect. Control group rats were treated with 10 ml/kg of distilled water. Experimental group rats were treated with 10 ml/kg of 100% swellfish extract prepared in Example <1-1>, 10 ml/kg of 100% swellfish extract prepared in Example <l-3> or 10 ml/kg of 100% swellfish extract prepared in Example <l-4>.

Sprague-Dawley rats (males) were allowed to take solid feed and tap water freely and adapted for 4 days. After 18 hours of fasting, the rats were treated with test samples. 30 minutes later, alcohol was orally administered to the rats (3 g/kg) . Blood samples were taken after 1 and 3 hours from the orbits and after 5 hours from the hearts. The blood samples were centrifuged at 3000 rpm for 20 minutes to separate serum. Then, ethanol and acetaldehyde concentrations were measured by using a kit (Roche) . Blood ethanol and blood acetaldehyde measured thereby were presented by w/v% and mg% . The concentrations were changed over the time and the statistic analysis was performed by student t-test (paired, independent) . The experiment was confirmed to be successfully done by observing that the blood alcohol level in the control group not treated with the sample of the present invention was reduced over the time as normally as expected from one hour after alcohol intake (3 g/kg) .

* Mean ± standard deviation

As shown in Table 1, the above results indicate that blood alcohol and blood acetaldehyde were reduced over the time more significantly by the swellfish protease extract than by the swellfish hot-water extract or swellfish ethanol aqueous solution extract.

Therefore, the swellfish protease extract of the present invention was proved to have better hangover treating effect than swellfish hot-water extract and swellfish ethanol extract. Experimental Example 2: Hangover treating effect of the swellfish protease extract containing artichoke

To investigate hangover treating effect of the swellfish protease extract containing artichoke, animal tests were performed by the same manner as described in Experimental Example 1.

40 Sprague-Dawley rats were grouped by 10, followed by animal tests examining hangover treating effect. Samples used for the test were 100% swellfish extract (10 mg/kg) of Example <1-1>, 100% artichoke extract (10 mg/kg) of Example <l-5>, 15% swellfish extract (10 mg/kg) of Example <l-2> and 100% swellfish extract (10 mg/kg) of Example <l-2> (6.7 times the 15% extract).

* Mean ± standard deviation

As a result, the group treated with 15% swellfish extract containing artichoke did not exhibit statistically significant hangover treating effect, but blood alcohoL level was reduced over the time compared with those of the groups treated with swellfish extract not containing artichoke and artichoke extract, for example blood alcohol level after one hour of the administration was 0.203±0.026 w/v%, blood alcohol level after 3 hours of the administration was 0.06±0.012 w/v%, and blood alcohol level after 5 hours of the administration was 0.045±0.015 w/v% . The group treated with 100% swellfish extract containing artichoke did not exhibit statistically significant effect, either, but blood alcohol level was reduced compared with those of the groups treated with swellfish extract not containing artichoke and artichoke extract, for example blood alcohol level after one hour of the administration was 0.220+0.023 w/v%, blood alcohol level after 3 hours of the administration was 0.071±0.014 w/v%, and blood alcohol level after 5 hours of the administration was 0.074±0.022 w/v%, which was though lower than the levels shown in the group treated with 15% swellfish extract (see Table 2 and Fig. 1) . Blood acetaldehyde level was also investigated in each group. In the group treated with 15% swellfish extract containing artichoke, blood acetaldehyde level after one hour from the administration was 0.534+0.084 w/v%, blood acetaldehyde level after 3 hours of the administration was 0.24910.050 w/v% and blood acetaldehyde level after 5 hours of the administration was 0.154+0.026 w/v%, which were more significant down-regulation than those in the groups treated with swellfish extract not containing artichoke and artichoke extract. In the group treated with 100% swellfish extract containing artichoke, blood acetaldehyde level after one hour from the administration was 0.275±0.014 w/v%, blood acetaldehyde level after 3 hours of the administration was 0.158±0.039 w/v% and blood acetaldehyde level after 5 hours of the administration was 0.128±0.024 w/v%, which were more significant reducing effect than those in the groups treated with swellfish extract not containing artichoke and artichoke extract (see Table 2 and Fig. 2).

Therefore, the swellfish protease extract containing artichoke of the present invention was confirmed to have approximately 50% hangover treating effect after 1 and 3 hours of the alcohol administration in the group treated with the 100% extract.

The Manufacturing Examples of the composition containing the swellfish extract of the present invention as an active ingredient are described hereinafter.

Manufacturing Example 1: Preparation of pharmaceutical formulations

<!-!> Preparation of powders

Extract of Example <l-2> 2 g

Lactose 1 g

Powders were prepared by mixing all the above components, which were filled in airtight packs according to the conventional method for preparing powders.

<l-2> preparation of tablets

Extract of Example <l-2> 100 mg Corn starch 100 rag

Lactose 100 mg

Magnesium stearate 2 mg Tablets were prepared by mixing all the above components by the conventional method for preparing tablets.

<l-3> Preparation of capsules

Extract of Example <l-2> 100 mg

Corn starch 100 mg

Lactose 100 mg Magnesium stearate 2 mg Capsules were prepared by mixing all the above components, which were filled in gelatin capsules according to the conventional method for preparing capsules.

<l-4> Preparation of pills

Extract of Example <l-2> 1 g

Lactose 1.5 g

Glycerin 1 g

Xylitol 0.5 g Pills were prepared by mixing all the above components according to the conventional method for preparing pills. Each pill contained 4 g of the mixture.

<l-5> Preparation of granules Extract of Example <l-2> 150 mg

Soybean extract 50 rag

Glucose 200 mg

Starch 600 mg

All the above components were mixed, to which 100 mg of 30% ethanol was added. The mixture was dried at 60 "C and the prepared granules were filled in packs.

Manufacturing Example 2: Preparation of foods

Foods containing the swellfish extract of the present invention were prepared as follows. <2-l> Preparation of seasonings

Health enhancing seasonings were prepared by mixing 20-95 weight part of the swellfish extract of Example <1- 1> with seasonings according to the conventional method.

<2-2> Preparation of flour food

0.5 ~ 5.0 weight part of the swellfish extract of

Example <1-1> was added to flour. Health enhancing foods such as bread, cake, cookies, crackers and noodles were prepared with the flour mixture according to the conventional method.

<2-3> Preparation of dairy products 5 - 10 weight part of the swellfish extract of Example <1-1> was added to milk. Health enhancing dairy products such as butter and ice cream were prepared with the milk mixture according to the conventional method.

<2-4> Preparation of Sun-Sik

Brown rice, barley, glutinous rice and Yulmu (Job's tears) were gelatinized according to the conventional method, dried and pulverized to obtain 60-mesh powders.

Black soybean, black sesame and wild sesame were steamed and dried according to the conventional method and pulverized to obtain 60-mesh powders.

The swellfish extract of Example <1-1> was concentrated under reduced pressure, spray-dried and pulverized to obtain 60-mesh dry powders. Sun-Sik was prepared by mixing the dry powders of the grains, seeds and the swellfish extract of Example <1-1> according to the below ratio.

Grains (brown rice: 30 weight part, Yulmu: 15 weight part, barley: 20 weight part) , Seeds (wild sesame: 7 weight part, black soybean: 8 weight part, black sesame: 7 weight part),

Dry powders of the swellfish extract of Example <1- 1> (3 weight part),

Ganoderma lucidum (0.5 weight part), Rehmannia glutinosa (0.5 weight part)

Manufacturing Example 3: Preparation of beverages <3-l> Preparation of health beverages

Extract of Example <l-2> 1000 rag Citric acid 1000 mg

Oligosaccharide 100 g

Purified water up to 900 mi

The above constituents were mixed according to the conventional method for preparing health beverages. The mixture was heated at 85°C for 1 hour with stirring and then filtered. The filtrate was loaded in 2 liter sterilized containers, which were sealed and sterilized again, stored in a refrigerator until they would be used for the preparation of a composition for health beverages. The constituents appropriate for favorite beverages were mixed according to the preferred mixing ratio but the composition ratio can be adjusted according to regional and national preferences, etc.

Those skilled in the art will appreciate that the conceptions and specific embodiments disclosed in the foregoing description may be readily utilized as a basis for modifying or designing other embodiments for carrying out the same purposes of the present invention. Those skilled in the art will also appreciate that such equivalent embodiments do not depart from the spirit and scope of the invention as set forth in the appended claims .

Claims

[CLAIMS]

[Claim l]

A manufacturing method of a swellfish extract comprising the following steps:

1) separating swellfish flesh from swellfish:

2) reacting the swellfish flesh of step 1) with enzyme: and

3) obtaining distillate by distillation with the enzyme reaction product of step 2) .

[Claim 2]

The manufacturing method according to claim 1, wherein the enzyme of step 2) is protease.

[Claim 3]

The manufacturing method according to claim 2, wherein the protease content is 0.1-0.2%, reaction temperature is 25-50^°C and reaction time is 12-36 hours.

[Claim 4]

The manufacturing method according to claim 1, wherein the temperature for distillation in step 3) is up to 100^°C and the distillation continues until the volume of enzyme reaction product becomes 1/3-1/2. [Claim 5]

The manufacturing method according to claim 1, wherein the step of aging the filtrate after adding artichoke powder to the distillate of step 3) and filtering the distillate is additionally included.

[Claim β]

The manufacturing method according to claim 5, wherein the filtering was performed by using 1,000 - 1,400 mesh net.

[Claim 7]

The manufacturing method according to claim 5, wherein the artichoke powder is added by 2 ~ 8 q/ i .

[Claim 8]

The manufacturing method according to claim 5, wherein the temperature for aging is 40 ~ 60 °C and time for aging is 5 ~ 20 hours.

[Claim 9]

A swellfish extract prepared by the method of claim 1.

[Claim 10] A pharmaceutical composition for treating hangover, comprising the swellfish extract of claim 9 as an active ingredient.

[Claim ll] A method for treating hangover containing the step of administering the pharmaceutically effective dose of the swellfish extract of claim 9 to a subject.

[Claim 12] A use of the swellfish extract of claim 9 for the preparation of a pharmaceutical composition for treating hangover.

[Claim 13] A health food for treating hangover containing the swellfish extract of claim 9 as an active ingredient.

[Claim 14]

A use of the swellfish extract of claim 9 for the preparation of health food for treating hangover.