KR20100060123A - Pharmaceutical composition for preventing or treating parkinson's diseases comprising a ginger extract or shogaol - Google Patents

Abstract

PURPOSE: A composition containing ginger extract or shogaol is provided to prevent or treat Parkinson's disease. CONSTITUTION: A pharmaceutical composition for preventing or treating Parkinson's disease contains ginger extract or shogaol and a pharmaceutically acceptable carrier. The composition is used in the form of a powder, granule, tablet, capsule, suspension, emulsion, or syrup. A method for extracting ginger extract comprises: a step of extracting ginger with C1-C4 alcohol; a step of adding water and n-hexane to the extract; and a step of adding ethyl acetate to an aqueous layer to extract and to separate ethyl acetate layer.

Description

Pharmaceutical composition for preventing or treating Parkinson's diseases comprising a ginger extract or shogaol}

The present invention is a ginger extract or shogaol; And a pharmaceutically acceptable carrier, the present invention relates to a pharmaceutical composition for preventing or treating Parkinson's disease.

Parkinson's disease is a chronic progressive neurological disease and one of the representative refractory diseases. Parkinson's disease is caused by the sudden degeneration or a significant decrease in the number of cells that produce the neurotransmitter dopamine in the substantia nigra area of the midbrain. The cause is not yet known in detail, but it is known that metabolism due to arteriosclerosis of the brain, carbon monoxide poisoning, drugs, hypoparathyroidism, trauma encephalitis, etc. are involved. Decreased dopamine in neurotransmitters disrupts the balance of the entire neurotransmitter system, resulting in tremor, stiffness, bradykinesia, and postural instability. Back symptoms appear.

Drugs for the treatment of Parkinson's disease include l-dopa preparations, dopamine receptor agonists, anticholinergic drugs, and eldepryl (delpyl). Most of these drugs control symptoms rather than cause treatment. It requires a constant and continuous medication. However, long-term administration of these drugs causes problems with drug side effects. For example, anticholinergic drugs may show autonomic nervous system abnormalities or mental dysfunctions, and thus are limited to continuous administration to older patients. In addition, in the case of the L-dopa formulation, the effect gradually decreases according to the long-term administration, and the side effects such as twisting the body and abnormal movements of the hands or feet are generated.

In addition, a surgical treatment such as high frequency nerve stimulation, that is, high frequency destruction or deep brain stimulation is also performed, but there is a problem that requires invasive surgery and also requires a lot of cost.

The present inventors conducted various searches for the prophylactic and / or therapeutic activity of Parkinson's disease on compounds derived from natural products, which have secured safety. As a result, it has been found that ginger extract has an excellent prophylactic and / or therapeutic activity of Parkinson's disease, and also shogaol, one of the pungent ingredients known to be contained in ginger, prevents Parkinson's disease and And / or have therapeutic activity.

Thus, the present invention is a ginger extract or shogaol; And it aims to provide a pharmaceutical composition for the prevention or treatment of Parkinson's disease, comprising a pharmaceutically acceptable carrier.

According to one aspect of the invention, ginger extract or shogaol; And a pharmaceutically acceptable carrier, a pharmaceutical composition for preventing or treating Parkinson's disease is provided.

Preferred dosage forms of the pharmaceutical composition may be oral formulations selected from the group consisting of powders, granules, tablets, capsules, suspensions, emulsions, and syrups.

It has been found by the present invention that ginger extract or shogaol has prophylactic and / or therapeutic activity for Parkinson's disease. Therefore, the pharmaceutical composition comprising shogaol as an active ingredient can be usefully applied for the prevention or treatment of Parkinson's disease.

By the present invention, it has been newly discovered that ginger extract or shogaol can prevent or treat Parkinson's disease. Protection of dopamine neurons after inducing dopamine neurocytotoxicity with 1-methyl-4-phenylpyridinium (MPP +) and 6-hydroxydopammine (6-OHDA) As a result of the activity test, Shogaol showed a dopamine cell protective activity. In addition, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)) causes Parkinson's disease in mice. , Pole test and dopaminergic neuron protective activity tests were performed to restore bradykinesia caused by MPTP when ginger extract or shogaol was administered, and also striatum. It showed excellent protective activity of dopaminergic neuron in and substantia nigra.

Accordingly, the present invention includes a pharmaceutical composition for preventing or treating Parkinson's disease, comprising ginger extract or shogaol and a pharmaceutically acceptable carrier.

The ginger extract is carried out an extraction process comprising the step of extracting ginger with an extraction solvent selected from the group consisting of C _{1 ~} C ₄ alcohols, n-hexane, ethyl acetate, n-butanol, chloroform, and a mixed solvent thereof Can be obtained. More preferably, the ginger extract may be an ethanol-extract obtained by extracting ginger with ethanol. The amount of the extractant used is not particularly limited, and for example, the extractant may be used in a ratio of about 1 to 10 times by volume, preferably about 1 to 5 times by volume, based on 1 weight of ginger powder sample. In addition, the extraction may be performed by extraction methods such as cold needle extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction for about 7 to 20 days, preferably about 7 to 10 days. Preferably, the extraction may be performed by cold extraction method at room temperature (about 25 ℃), and the extraction process may be performed once or multiple times, preferably about three times. The obtained extract can be concentrated under reduced pressure or dried under reduced pressure at a conventional method, for example, at about 20 to 100 ° C., preferably at about 30 to 70 ° C., to obtain a ginger extract in liquid or powder form.

The ginger extract may be obtained by performing an additional extraction process to increase the content of the active ingredient. That is, (a) extracting ginger with C _{1 ~} C ₄ alcohol; And (b) extracting by adding water and n-hexane to the extract obtained in step (a) and separating the obtained n-hexane layer (and further chromatographic fractionation if necessary). By this, a ginger extract having a high content of the active ingredient can be obtained. Also optionally (a) extracting ginger with an alcohol of C ₁ -C ₄ ; (b ') adding water and n-hexane to the extract obtained in step (a) to extract and separating the aqueous layer obtained; And (c) extracting by adding ethyl acetate to the aqueous layer obtained in step (b '), and separating the obtained ethyl acetate layer (and further chromatographic fractionation if necessary); Or (a) extracting ginger with an alcohol of C ₁ -C ₄ ; (b ') adding water and n-hexane to the extract obtained in step (a) to extract and separating the aqueous layer obtained; (c ') extracting by adding ethyl acetate to the aqueous layer obtained in step (b'), and separating the aqueous layer obtained; And (d) extracting n-butanol by adding n-butanol to the aqueous layer obtained in step (c '), and separating the resulting n-butanol layer or aqueous layer (and further chromatographic fractionation if necessary). By doing this, a ginger extract having a high content of the active ingredient can be obtained. Preferably, an extraction process comprising separating the ethyl acetate layer as described above, that is, the ethyl acetate fraction may be used.

The further extraction process (ie steps (b), (b '), (c), (c'), and (d)) may be carried out by cold extraction method at room temperature (about 25 ° C.), and also The extraction process may be performed once or plural times, preferably about three times. The obtained extract can be concentrated under reduced pressure at a conventional method, for example, at about 20 to 100 ° C., preferably at about 30 to 70 ° C., or lyophilized as necessary to obtain a ginger extract in liquid or powder form. have.

In addition, after performing the above additional extraction process, it is also possible to perform a fractionation process using silica gel column chromatography, if necessary. The fraction was prepared by increasing the polarity of the mixed solvent of hexane and ethyl acetate (Hexane: EtOAc = 30: 1 →→ 1: 11) and the mixed solvent of ethyl acetate and methanol (EtOAc: MeOH = 25: 1 →→ 1: 2). It may also be carried out by repeating the process of eluting with a thin eluting solvent system several times.

The ginger extract can also be obtained using supercritical extraction. Supercritical extraction is carried out at a pressure of 60 to 350 bar, more preferably at about 300 bar, for 5 minutes to 24 hours, more preferably at about 6 hours, at 30 to 80 ° C., more preferably at about 50 ° C. Can be performed. In addition, the flow rate of the carbon dioxide can be maintained at 10 to 50 g / min, more preferably about 30 g / min, but is not particularly limited. The supercritical extraction may be performed once or multiple times (for example, 2 to 4 times). The carbon dioxide containing the ginger extract is introduced in the middle of the separator and the pressure drops to about 50-60 bar, so that the solubility drops sharply. It is wrapped by the extract at the bottom and separated into liquid carbon dioxide and gaseous carbon dioxide at the top. The gaseous carbon dioxide at the top is liquefied by a cooler across a filter such as a charcoal filter and circulated back to the extractor through a pump.

In addition, in one embodiment of the present invention, there is provided a pharmaceutical composition comprising shogaol as an active ingredient. The shogaol is also called 6-shogaol, and its chemical name is ( E ) -1- (4-hydroxy-3-methoxyphenyl) dec-4-en-3-one [( E )- 1- (4-hydroxy-3-methoxyphenyl) dec-4-en-3-one], which has the structure of Formula 1 below.

The shogaol may be separated from ginger, and various synthetic methods are known, including, for example, EP EP696958.

The pharmaceutical compositions according to the invention can be in various forms, including pharmaceutically acceptable carriers, for example oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injections. It may be formulated in the form of a solution. Especially preferably, it may be formulated in an oral dosage form.

The pharmaceutically acceptable carrier is lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like. Also included are diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, and the like. Oral solid preparations include tablets, pills, powders, granules, capsules and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose or lactose. ), Gelatin, and the like, and may include a lubricant such as magnesium stearate, talc, and the like. Oral liquid preparations include suspensions, solvents, emulsions, syrups, and the like, and may include water, diluents such as liquid paraffin, wetting agents, sweeteners, fragrances, preservatives, and the like. Parenteral preparations include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, and non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and ethyl. Injectable esters such as oleate and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The dosage of the ginger extract or shogaol contained in the pharmaceutical composition of the present invention depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. For example, the shogaol may be administered at a dose of 0.01 to 500 mg / kg, preferably 10 to 100 mg / kg per day, and the administration may be administered once or several times a day. In addition, ginger extract may be administered in a dose of 0.01 to 500 mg / kg, preferably 10 to 100 mg / kg per day, the administration may be administered once or several times a day. In addition, the pharmaceutical composition of the present invention may comprise 0.001 to 50% by weight of the shogaol or ginger extract based on the total weight of the composition.

Hereinafter, the present invention will be described in more detail through Examples and Test Examples. However, these Examples and Test Examples are for illustrating the present invention, and the scope of the present invention is not limited to these Examples and Test Examples.

Example 1 Preparation of Ginger Extract

1 kg of ginger was ground, 5 liters of ethanol was added, and ultrasonic extraction was performed for 1 hour, followed by filtration to separate the filtrate. The solid obtained by the filtration was put back into ethanol and the ultrasonic extraction was performed for 1 hour, and the filtrate was separated again by filtration. The process was repeated two more times. The obtained filtrates were combined and concentrated under reduced pressure to remove the solvent, followed by lyophilization to completely remove moisture to obtain 200 g of ginger extract.

200 g of the ethanol-extract obtained above was added to 1000 ml of distilled water, and then uniformly well suspended. Then, 1000 ml of n-hexane was added thereto, and the n-hexane layer was separated through a fractionation process. The resulting n-hexane layer was concentrated under reduced pressure to remove hexane and dried through lyophilization. This process was repeated three times to obtain 60 g of hexane fraction. In addition, 1000 ml of ethyl acetate was added to the remaining aqueous layer to separate the ethyl acetate layer. The ethyl acetate layer was concentrated under reduced pressure to remove the solvent, and then completely freed of water through lyophilization. This process was repeated three times to obtain 50 g of an ethyl acetate fraction. In addition, n-butanol layer was separated by adding 1000 ml of n-butanol to the remaining aqueous layer. The obtained n-butanol layer was concentrated under reduced pressure to remove the solvent, and then completely dried by lyophilization. This process was repeated three times to obtain 18 g of n-butanol fraction. In addition, the remaining aqueous layer was concentrated under reduced pressure to remove the solvent and then lyophilized to obtain 43 g of a water fraction.

Example 2. Preparation of Ginger Extract

Ginger extract was prepared using a supercritical extraction method. Ginger was ground, 200 g of the dried sample was filled into a supercritical extractor, and extracted twice for 6 hours at 300 bar and 50 ° C. At this time, the flow rate of carbon dioxide was maintained at 30 g / min, the pressure in the middle of the separator was set to 50-60 bar, the temperature of the heating jacket at the top was set to 40 ℃, the temperature of the cooling jacket at the bottom of 5 ℃ or less Set to. The gaseous carbon dioxide at the top of the separator was liquefied by the cooler across the charcoal filter and circulated back through the pump to the extractor. Supercritical extraction was performed as above to obtain 4.32 g of ginger extract.

Test Example 1. Evaluation of protective effect of Shogaol and Ginger extracts in rat fetal brain brain cells by neurotoxicity of MPP + (1-methyl-4-phenylpyridinium) and 6-OHDA (6-hydroxy-dopamine)

Female Sprague-Dawley rats (2 weeks old) were distributed and used, and Shogaol was purchased from WAKO (Japan).

Midbrain tissue from Sprague-Dawley rat (2 week old) fetuses was detached and mechanically dissociated using forceps. Trypsin treatment was used to count cells and seed them on coverslips pre-coated with poly-L-Lysine (PLL), then in a 37 ° C incubator with 5% CO ₂ and 95% air. Proliferation for 5 days. Diluted with Shogaol 0.01μM, 0.1μM in medium without fetal bovine serum (FBS) or ginger extract (ethanol extract, hexane fraction, ethyl acetate fraction, butanol fraction, water obtained in Example 1) Fractions) were treated by dilution, MPP + was treated with 10 μM for 23 hours after 1 hour of shogaol treatment and 10 μM for 6 hours after 6 hours of Shogaol treatment. Fixed with 4% paraformaldehyde (PFA) and washed with phosphate buffered saline (PBS).

(1) Evaluation of Protective Activity of Shogaol-Immunohistochemistry

The cells fixed with 4% PFA were washed with PBS and dehydrated with 1% hydrogen peroxide for 15 minutes, followed by Tyrosine hydroxylase (TH, millipore, rabbit origin 1 :) containing PBS, 3% Triton X-100, and normal goat serum. 2000) were reacted with the cells overnight. After a certain period of time, the biotinylated anti-rabbit (vector, goat origin) was reacted with a secondary antibody, and then developed using a diaminobenzidine (DAB) through an ABC reaction (ABC kit, vector). After removing the cover slip on the slide was mounted using a gel mount and the number of cells was measured. The result is the same as that of FIGS. 1A and 1B.

1a shows the dopaminergic protective effect of shogaol on neurotoxicity by MPP +. In the MPP + group, the number of dopamine-positive cells was 44.25 ± 7.61% compared to the control group, which significantly reduced the number of dopamine cells (p <0.01), and when treated with shogaol, the concentration was 91.50 ± 3.38% at 0.01 μM. The dopamine cell protection effect was significant (p <0.05).

Figure 1b shows the dopaminergic protective effect of Shogaol on neurotoxicity by 6-OHDA. 6-OHDA group showed 34.00 ± 5.77% dopamine-positive cell counts compared to the control group, which significantly reduced the number of dopamine cells (p <0.001). The Shogaol-treated group was 57.25 ± 0.01 μM. The number of dopamine positive cells was increased by 5.65% compared to 6-OHDA group.

(2) Evaluation of Protective Activity of Ginger Extract-Immunohistochemistry

After the color development by immunohistochemistry in the same manner as in (1), the result of measuring the number of cells is as shown in Figs. 2a and 2b.

Figure 2a shows the dopamine cell protective effect of ginger extract on neurotoxicity by MPP +. In the MPP + group, the number of dopamine-positive cells was 44.25 ± 7.61% compared to the control group, which significantly decreased the number of dopamine cells (p <0.01), ginger extract (ethanol extract), hexane fraction, ethyl acetate fraction, butanol When the fractions and water fractions were treated at 100 ug / ml, the dopamine-positive cell count was increased to 65.20 ± 3.45%, 71.41 ± 6.32%, 76.60 ± 6.15%, 58.32 ± 7.22%, 57.17 ± 5.33%, respectively, compared to the MPP + group. Indicated.

Figure 2b shows the dopaminergic protection effect of ginger fraction on neurotoxicity by 6-OHDA. 6-OHDA group showed 34.00 ± 5.77% dopamine-positive cell count compared to the control group, which significantly reduced the number of dopamine cells (p <0.001). Ginger extract (ethanol extract), hexane fraction, ethyl acetate fraction , Butanol fraction and water fraction were treated with 100 ug / ml, respectively, with 54.20 ± 4.31%, 62.50 ± 6.94%, 64.54 ± 4.67%, 49.61 ± 5.64%, and 45.11 ± 5.21%, respectively. It showed a tendency to increase.

Test Example 2 Protection of Ginger Extract and Shogaol in C57BL / 6 Mice Induced Parkinson's Disease by Administration of MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) Effect evaluation

Seven-week-old C57BL / 6 male mice (19-22 g) were fed and reared for more than a week in the animal breeding room of the Graduate School of East-West Medical Science, Kyung Hee University. The water and feed were freely ingested. 2 ° C.), humidity (53 ± 3%) and contrast cycle (12 hours) were automatically adjusted. Shogaol was purchased from WAKO (Japan).

(1) Protective Effects of Shogaol in Parkinson's Disease Model by MPTP Administration

Mice were divided into 3 groups, 6 of each group. Group 1 (control) and group 2 (MPTP) received 10% dimethyl sulfoxide orally once daily for 5 days at 5 mL / kg of mouse, and group 3 (shogaol group) received 10% dimethyl sulfoxide. Shogaol dissolved in the side was administered orally once a day for 5 days in an amount of 10 mg / kg. Two hours after oral administration, the first group (control group) was intraperitoneally administered saline solution at 5 mL per kg body weight for 5 days, and the second and third groups were dissolved in saline solution at a concentration of 30 mg / kg MPTP for 5 days. Intraperitoneal administration.

(1-1) pole test

On the day after the end of the five-day administration, a pole test was performed on a rod of 50 cm in height and 1 cm in diameter. The C57bl / 6 mouse was placed on the rod with the head facing up and the time taken for the mouse to turn 180 ° around the top until the four legs touched the ground. Each experiment was performed three times, and then this experiment was performed five times, and the results are shown in FIG. 3.

As can be seen in Figure 3, when administered Shogaol T-la [% of control] is 99.10 ± 8.11 seconds, similar to the control level without MPTP administration, Ol could restore almost normal levels of bradykinesia caused by MPTP. (p <0.05)

(1-2) Evaluation of Protective Activity of Dopamine Cells

After the mice of each group who completed the pole test were killed, brain tissues (striatum and substantia nigra) were separated. Dehydrated brain tissue was dehydrated with hydrogen peroxide, followed by overnight reaction with Tyrosine hydroxylase (TH, millipore, rabbit origin 1: 2000) as a primary antibody, and then biotinylated anti-rabbit (vector, goat origin) as a secondary antibody. After the ABC reaction (ABC kit, vector) was developed using Diaminobenzidine (Diaminobenzidine). Dopamine cell protection was determined by measuring the optical density in the striatum and the number of TH positive cells in the black matter. The results are the same as in Figs. 4a and 4b.

As can be seen from Figure 4a and Figure 4b, when the shogaol administered in the striatum optical density was 80.11 ± 1.97% compared to the control, it can be seen that the protective activity of the dopamine cells significantly more than the MPTP administration group The percentage of TH-positive cells in the vaginal group was 70.30 ± 4.86 compared to the control group, which significantly increased the number of TH-positive cells compared to the MPTP group (p <0.05). As a result, shogaol can be seen to show excellent protective activity of dopamine cells in the striatum and substantia nigra.

(2) Protective Effect of Ginger Extract in Parkinson's Disease Model by MPTP Administration

Mice were divided into 3 groups, 10 of each group. Group 1 (control) and group 2 (MPTP) received 10% dimethyl sulfoxide orally once daily for 5 days at 5 mL / kg of mouse, and group 3 (shogaol group) received 10% dimethyl sulfoxide. Ginger extract dissolved in the side (extract prepared in Example 2) was administered orally once a day for 5 days in an amount of 50 mg / kg. Two hours after oral administration, the first group (control group) was intraperitoneally administered saline solution at 5 mL per kg body weight for 5 days, and the second and third groups were dissolved in saline solution at a concentration of 30 mg / kg MPTP for 5 days. Intraperitoneal administration.

(2-1) pole test

The day after the end of the five-day administration, the behavior test was performed in the same manner as in (1-1), and the results are shown in FIG.

As can be seen in Figure 5, T-la is 107.48 ± 7.32 seconds when the ginger extract is administered, it can be seen that the ginger extract restores bradykinesia caused by MPTP.

(2-2) Evaluation of Protective Activity of Dopamine Cells

After the mice of each group who completed the pole test were killed, brain tissues (striatum and substantia nigra) were separated. The activity of the isolated brain tissues was evaluated in the same manner as in (1-2), and the results are shown in FIGS. 6A and 6B.

As can be seen from Figure 6a and Figure 6b, when the ginger extract was administered, the optical density in the striatum was 84.21 ± 1.48% compared to the control, it was confirmed that the protective activity of the dopamine cells significantly more than the MPTP administration group. (p <0.01), the percentage of TH-positive cells in black matter was 62.20 ± 3.67% compared to the control group (p <0.05). As a result, the ginger extract can be seen to show the protective activity of dopamine cells in striatum and substantia nigra.

Figure 1a shows the results of measuring the protective effect of shogaol dopaminergic cells in rat fetal midbrain cells against neurotoxicity of MPP +.

Figure 1b shows the result of measuring the dopaminergic protective effect of shogaol in the rat fetal brain brain cells on the neurotoxicity of 6-OHDA.

Figure 2a shows the results of measuring the dopaminergic cell protective effect of ginger extract in rat fetal midbrain cells against neurotoxicity of MPP +.

Figure 2b shows the results of measuring the dopaminergic cell protective effect of the ginger extract in rat fetal midbrain cells against neurotoxicity of 6-OHDA.

FIG. 3 shows the results of Shogaol's pole test on C57BL / 6 mice induced with Parkinson's disease by MPTP administration.

Figure 4a shows the results of measuring the inhibitory activity of Shogaol against the optical density reduction of the striatum in C57BL / 6 mice induced Parkinson's disease by MPTP administration.

Figure 4b shows the results of measuring the inhibitory activity of shogaol against the reduction of tyrosine hydroxylase positive cells of substantia nigra in C57BL / 6 mice induced with Parkinson's disease by MPTP administration.

Figure 5 shows the results of a pole test of ginger extract on C57BL / 6 mice induced Parkinson's disease by MPTP administration.

Figure 6a shows the results of measuring the inhibitory activity of ginger extract against the optical density of the striatum in C57BL / 6 mice induced Parkinson's disease by MPTP administration.

Figure 6b shows the results of measuring the inhibitory activity of ginger extract against dopamine positive cell reduction of black matter in C57BL / 6 mice induced Parkinson's disease by MPTP administration.

Claims (9)

Ginger extract or shogaol; And a pharmaceutically acceptable carrier, wherein the pharmaceutical composition for preventing or treating Parkinson's disease. The pharmaceutical composition of claim 1, wherein the dosage form of the composition is an oral dosage form selected from the group consisting of powders, granules, tablets, capsules, suspensions, emulsions, and syrups. The extract according to claim 1 or 2, wherein the ginger extract is selected from the group consisting of C ₁ to C ₄ alcohols, n-hexane, ethyl acetate, n-butanol, chloroform, and a mixed solvent thereof. Pharmaceutical composition, characterized in that obtained by performing an extraction process comprising the step of extracting. The pharmaceutical composition according to claim 1 or 2, wherein the ginger extract is obtained by extracting ginger with ethanol. The method of claim 1 or 2, wherein the ginger extract (a) extracting ginger with an alcohol of C _{1 ~} C ₄ ; And (b) extracting by adding water and n-hexane to the extract obtained in step (a) and separating the obtained n-hexane layer. The method of claim 1 or 2, wherein the ginger extract (a) extracting ginger with an alcohol of C _{1 ~} C ₄ ; (b ') adding water and n-hexane to the extract obtained in step (a) to extract and separating the aqueous layer obtained; And (c) extracting by adding ethyl acetate to the aqueous layer obtained in step (b '), and separating the obtained ethyl acetate layer. The method of claim 1 or 2, wherein the ginger extract (a) extracting ginger with an alcohol of C _{1 ~} C ₄ ; (b ') adding water and n-hexane to the extract obtained in step (a) to extract and separating the aqueous layer obtained; (c ') extracting by adding ethyl acetate to the aqueous layer obtained in step (b'), and separating the aqueous layer obtained; And (d) extracting n-butanol by adding n-butanol to the aqueous layer obtained in step (c '), and separating the obtained n-butanol layer or aqueous layer. The pharmaceutical composition according to claim 1 or 2, wherein the ginger extract is obtained through supercritical extraction at 30 to 80 ° C. for 5 minutes to 24 hours at a pressure of 60 to 350 bar. The pharmaceutical composition according to claim 8, wherein the ginger extract is obtained by supercritical extraction 2 to 4 times at a pressure of about 300 bar and at about 50 ° C. for about 6 hours.

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