KR101461591B1 - Pharmaceutical composition and functional food for prevention or treatment of thrombosis - Google Patents

Abstract

The present invention relates to a pharmaceutical composition or health functional food composition for preventing or treating thrombosis, which comprises a compound represented by the following general formula (1), which can be separated from a patient, or a pharmaceutically acceptable salt thereof as an active ingredient. Accordingly, the composition effectively inhibits platelet aggregation, and thus has an excellent effect for preventing or treating thrombosis.
[Chemical Formula]

Description

[0001] The present invention relates to a pharmaceutical composition and a functional food composition for preventing or treating thrombosis,

The present invention relates to a pharmaceutical composition or a health functional food composition for preventing or treating thrombosis comprising, as an active ingredient, a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof,

Thrombus is a phenomenon that occurs due to inadequate occurrence of normal blood coagulation function, that is, the thrombus formation system mainly composed of fibrin is overcome the activity of thrombolytic system acting on fibrin removal. As a result, various types of diseases appear. Among them, stroke and cardiovascular diseases are the most common diseases. These are the three diseases that we often encounter with cancer. Cardiovascular disease is a disease that involves heart-related diseases (myocardial infarction, hypertension, heart failure, arrhythmia, arteriosclerosis) and vascular disease (stroke, peripheral vascular disease). According to statistics of the World Health Organization (WHO) Despite the remarkable progress, it has been reported that the incidence and prevalence increased steadily over the past 30 years, and it is a kind of fatal disease that accounts for a very high rate of mortality due to cardiovascular system diseases in Korea and worldwide, accounting for about 30% .

These cardiovascular diseases are most closely related to blood cholesterol, changes in blood components due to changes in lipid composition, and excessive mental tension, which are closely related to blood. Under normal conditions, the blood does not coagulate in the blood vessels, but when bleeding occurs, blood coagulation occurs as one of the body defense functions. However, when blood vessels are damaged due to changes in blood components, or if the blood flow is not smooth due to narrowing of the inner diameter of the blood vessels due to atherosclerosis, thrombus is formed to prevent the coronary artery or fine blood vessels supplying blood to the heart through the bloodstream Resulting in brain or cardiovascular disease. In addition, since the risk of recurrence is high in view of disease progression, lifelong treatment is often required.

Platelets, which play an important role in thrombus formation, are blood cells involved in hemostasis. They are made from bone marrow, have no nucleus, and have a disk shape with a radius of 3 ㎛ to 4 ㎛. When the blood vessels are damaged, the platelets adhere to the basement membrane and the collagen. At this time, platelets are said to be 'activated' and secrete substances that directly or indirectly induce platelet aggregation. Through this step, thrombin is produced with activation of endogenous coagulation cascade, thrombin converts fibrinogen to fibrin, and fibrin is stabilized by thrombin-activated coagulation factor. Under normal conditions, the thrombus produced by this fibrin is dissolved and restored to normal blood vessels, but in abnormal conditions, it causes thrombosis.

Thrombosis may be caused by atherothrombotic diseases, phlebothbombosis, hepatic protal vein thrombitis, pulmonary thromboembolism, chronic limbischemia, varicose vein, deep vein thrombosis deep vein thrombosis diseases, anginapectoris, cerebral infarction, cerebral hemorrhage, and also causes infection or vascular injury, postoperative complications, and coagulative diseases.

On the other hand, arteriosclerosis is a disease in which hypertrophy or tissue degeneration arises in the arterial wall and hardens (hardens). As the inner diameter of the artery becomes thicker and the inner diameter becomes narrower, the coronary artery supplying oxygen and various nutrients, , Which causes blood flow disorder, which is one of the major diseases associated with aging. Atherosclerosis is atherosclerosis, which is caused by fibrosis around the atheroma caused by excessive cell proliferation in the inner lining of the artery, and the vessel becomes harder. The term atherosclerosis is sometimes called arteriosclerosis.

Arteriosclerosis begins around the age of 10 years, and blood flow disorder occurs in the late 40s. In some cases, the fibrous membrane ruptures, resulting in blood clots in the blood vessels. Hemorrhage occurs in the atheroma and the blood vessel diameter rapidly narrows and causes various diseases. Atherosclerosis is apt to occur in the cerebral artery or coronary artery. In the case of cerebral artery sclerosis, it causes headache, dizziness, mental disorder and causes the cerebral palsy. In the case of coronary atherosclerosis, it causes pain and arrhythmia in the heart part and causes angina and myocardial infarction Is known to be. In addition, this causes heart disease, cerebral hemorrhage, and the like, and diseases caused by arteriosclerosis are becoming a major cause of death in modern society. In addition, arteriosclerosis is closely related to the development and progression of diseases such as obesity (overweight), thrombosis, hypercoagulability and thrombotic conditions (arterial and venous), metabolic syndrome such as obesity, Causes or aggravates chronic complications.

Arteries are divided into aorta, middle artery, and small artery, and are composed of three layers of intima, middle membrane and outer membrane. Especially, atherosclerosis is mainly developed in elasticity and muscular artery. Vascular smooth muscle cells that contract vasoconstriction and enlargement can migrate to the inner membrane after stimulation and have receptors for LDL. Under normal conditions, the proliferation is regulated by a very strict mechanism, but abnormally hyperplasia may cause vascular disease. In addition, vascular smooth muscle cells induce vascular restenosis in the treatment of ischemic heart disease represented by angina pectoris and myocardial infarction. In order to prevent this, anti-hypertrophy agents, Etc. have been administered, but they have not shown sufficient clinical effects.

Thrombosis therapy is classified into prevention of platelet aggregation, prevention of blood clotting, and dissolution of thrombus, and anticoagulation is the most effective method for prevention of double thrombosis.

Among the drugs that inhibit platelet coagulation function are non-steroidal anti-inflammatory drugs such as aspirin and indomethacin, which inhibit the metabolism of prostaglandin and reduce the generation of thromboxane or reduce the amount of cAMP in platelets . In particular, aspirin inhibits the synthesis of thromboxane A ₂ by irreversibly acetylating cyclooxygenase, which synthesizes prostaglandins, a platelet aggregation inducer, from arachidonic acid in cell membranes, Since there is no synthetic ability, the platelet aggregation inhibition effect is maintained until the platelets having a new enzyme appear, and the period of time is about 10 days.

However, nonsteroidal antiinflammatory drugs such as aspirin have excellent effects but have low selectivity and increase the risk of hemorrhage due to frequent gastrointestinal disorders, fatal side effects such as gastric perforation, agranulocytosis and aplastic anemia in the blood system, liver toxicity induction, There are disadvantages that cause side effects. To solve these problems, attempts have been made to develop medicines to interfere with gastric absorption, to administer medicines using injections, and to develop prodrugs that are metabolized and then activated in the liver. But did not have a significant effect on reducing the incidence of side effects.

Therefore, studies have been actively made to obtain platelet aggregation inhibiting components having excellent effects, which have no side effects as described above, from natural materials. Until now, antiplatelet clotting effect has been reported in natural products such as catechin, garlic, ginger, ginkgo extract, and ginseng of green tea. However, there is no antiplatelet clotting material showing good commercialization level. Therefore, it is necessary to study for the better detection of antiplatelet clotting material from natural products.

Under the circumstances described above, the present inventors studied a safe substance which is not harmful to the human body, which can be effectively used for prevention or treatment of thrombosis by inhibiting the platelet aggregation phenomenon. The compound represented by the formula (1) And exhibits an excellent inhibitory effect on platelet aggregation, thereby completing the present invention.

It is an object of the present invention to provide a pharmaceutical composition or a health functional food composition having an excellent effect for the prevention or treatment of thrombosis which comprises the compound represented by the formula (1) isolated from a crowd or a pharmaceutically acceptable salt thereof as an active ingredient will be.

In order to solve the above problems, the present invention provides a pharmaceutical composition for preventing or treating thrombosis, which comprises a compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Chemical Formula 1]

The compound represented by Formula 1 is preferably extracted from the spectra.

The extraction can be carried out through conventional methods known in the art. In one embodiment of the present invention, the compound represented by the above formula (1) was obtained from the spectra through the following method.

The crowned mass was immersed in water for 1 hour and then subjected to hot water extraction for 4 hours using a potter, followed by concentration under reduced pressure and lyophilization to obtain a spectral extract. The obtained extracts of the spectra were fractionated with dichloromethane and the mixture of dichloromethane fraction and methanol was subjected to silica gel column chromatography according to polarity to obtain small fractions of A1, A2, A3, A4, A5 and A6. A small fraction A2 of the above small fractions was further subjected to silica gel column chromatography (dichloromethane: methanol = 40: 1) to collect fractions having similar fluorescence according to the thin layer chromatography method, and three fractions of B1, B2, B3 and B4 . The B2 fraction was subjected to preparative thin layer chromatography (dichloromethane: methanol = 10: 1) to obtain compound fractions C1 and C2. Thereafter, the B3-old fraction and the compound fraction C1 were again subjected to preparative RP-HPLC to separate the compound represented by the above formula (1).

On the other hand, the term "Crassirhizomae Rhizoma" used in the present invention is a perennial herbaceous plant of the bracken, and mainly uses young leaves, and rootstock is used as a medicinal herb. The crowd is known to exhibit antiparasitic, antipyretic, detoxifying, cold virus inhibiting, antibacterial and anticancer activities, and moon water has an inhibitory action against skin fungi.

The compound represented by formula (1) of the present invention can be used in the form of a pharmaceutically acceptable salt. Examples of such salts include acid addition salts formed by pharmaceutically acceptable free acids or metal salts formed by a base . Examples of the inorganic acid include hydrochloric acid, sulfuric acid, bromic acid, sulfurous acid, and phosphoric acid. Examples of the organic acid include citric acid, acetic acid, maleic acid, fumaric acid, gluconic acid, methanesulfonic acid, Can be used. The metal salts include alkali metal salts or alkaline earth metal salts, and sodium, potassium or calcium salts are useful.

The term "thrombosis " used in the present invention refers to a disease caused by a lump (loose blood) in the blood vessel, which is also called a thromboembolism, in particular, a blood vessel clogged by a thrombus. When a blood vessel is injured, the blood vessel contracts, and platelets adhere to the collagen fiber exposed to the wound, thereby releasing the vasoconstrictive substance. This causes more platelets to stick together, leading to aggregation of platelets, leading to vasoconstriction. Thrombosis can be classified into arterial thrombosis and venous thrombosis. Arterial thrombosis has symptoms such as acute myocardial infarction, stroke, pulmonary thrombosis, deep vein thrombosis, and acute peripheral artery occlusion. In addition, venous thrombosis has symptoms such as deep vein thrombosis, portal vein thrombosis, acute renal vein occlusion, cerebral sinus thrombosis, central retinal vein occlusion. In addition, the thrombosis may include arteriosclerosis.

It is preferable that the composition has platelet aggregation inhibiting activity.

According to one embodiment of the present invention, platelet aggregation induced by collagen, arachidonic acid, or thrombin is treated with a composition comprising the compound of Formula 1 to significantly inhibit the platelet aggregation phenomenon as compared with the negative control (Fig. 2 to Fig. 3). In addition, it was confirmed that platelet aggregation was significantly inhibited as compared with aspirin, which is a positive control group.

The term "prophylactic " as used in the present invention means any action which inhibits or delays disease by the administration of a composition containing the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof. The term "treatment" used in the present invention means all the actions of improving or ameliorating symptoms of a disease by administration of a composition containing the compound represented by the above-mentioned formula (1) or a pharmaceutically acceptable salt thereof.

The composition of the present invention may contain, for administration, a pharmaceutically acceptable carrier, excipient or diluent in addition to the above-described effective ingredients. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose , Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

The composition of the present invention may be formulated in the form of oral, granule, tablet, capsule, suspension, emulsion, syrup, aerosol or the like oral preparation, external preparation, suppository or sterilized injection solution according to a conventional method. In detail, when formulating, it can be prepared by using diluents or excipients such as fillers, weighing agents, binders, humectants, disintegrants, surfactants and the like which are generally used. Solid formulations for oral administration include, but are not limited to, tablets, pills, powders, granules, capsules, and the like. Such a solid preparation can be prepared by mixing at least one or more excipients such as starch, calcium carbonate, sucrose, lactose, gelatin and the like in the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration, liquid paraffin, and various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and tasks. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. As a base for suppositories, it is possible to use witepsol, macrosole, tween 61, cacao paper, laurin, glycerogelatin and the like.

The composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the desired method, and the dose may be determined depending on the condition and weight of the patient, The mode of administration, the route of administration, and the time, but may be suitably selected by those skilled in the art. The daily dose of the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof is preferably 1 mg / kg to 500 mg / kg, and may be administered once or divided into several times, if necessary.

The present invention also provides a health functional food composition for preventing or ameliorating thrombosis, which comprises a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Chemical Formula 1]

The health functional food composition may contain various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate etc.), pectic acid and its salts, alginic acid and its salts , Organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. And may also contain flesh for the production of fruit juices and vegetable drinks such as natural fruit juices and synthetic fruit juices. These components may be used independently or in combination. The health functional food composition may be in the form of any one of meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, drink, alcohol and vitamin complex Lt; / RTI >

In addition, the health functional food may further include food additives, and the suitability of the food functional food as a "food additive" is not limited to the corresponding items in general rules and general test methods approved by the Food and Drug Administration Shall be determined according to the relevant standards and standards.

Examples of the products that have been used in the above-mentioned "food additives" include natural products such as ketones, chemical products such as glycine, potassium citrate, nicotinic acid and cinnamic acid, sensory coloring matter, licorice extract, crystalline cellulose, high- - Mixed preparations such as a sodium glutamate preparation, a noodle-added alkaline agent, a preservative preparation, a tar coloring agent and the like.

Herein, the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof according to the present invention, which is added to the food during the production of the health functional food composition, can be appropriately added or decreased as needed, By weight to 100% by weight to 1% by weight to 15% by weight.

The composition comprising the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof isolated from the crowns according to the present invention effectively inhibits platelet aggregation and thus has an excellent effect for preventing or treating thrombosis.

Therefore, the composition is useful for a pharmaceutical composition or a health functional food composition for preventing or treating thrombosis.

1 is a schematic view showing a process of separating a compound represented by the formula (1) from a hot water extract of a hot water according to an embodiment of the present invention.
FIG. 2 is a graph comparing platelet aggregation inhibition effects of collagen-induced platelet aggregation according to an embodiment of the present invention (a) Compound 1 (Compound 1) and (b) positive control (Aspirin) Fig.
FIG. 3 is a graph comparing platelet aggregation inhibitory effects of (a) compound 1 (Compound 1) and (b) positive control (aspirin) against platelet aggregation induced by arachidonic acid according to an embodiment of the present invention FIG.

Hereinafter, the present invention will be described in more detail with reference to the following examples and experimental examples. However, the following examples and experimental examples are provided for illustrating the present invention, and the scope of the present invention is not limited thereto.

Hereinafter, reagents and devices used in the experiments are as follows.

1100 + G1958 API LC / MS (Agilent Technologies, Inc., Germany) was used as a mass spectrometer for molecular weight determination and INONA 400 NB NMR (Varian Co., USA) of Varian Corporation was used as a nuclear magnetic resonance spectrometer . The high performance liquid chromatography used for component analysis and separation was an Elite lachrom HPLC / DAD system (Hitachi High-Technologies Co., Tokyo, Japan); We used semi-prep and analytical combination consisting of L-2130 pump, L-2200 auto-sampler, L-2350 column oven, L-2455 diode array UV / VIS detector and EZchrom Elite software (version 3.3.1a). GECTOR semi-prep-C13 (4.6 × 360 mm, 15 μm) and HECTOR C13 (4.6 × 250 mm, 5 μm) were used for the high performance liquid chromatography column. Kieselgel 60 (70-230 mesh, Merck) was used as a stationary phase for column chromatography used for separation of components, Kieselgel 60 F254 (Merck) was used for thin layer chromatography analysis, and 10% anisaldehyde sulfuric acid solution was used for color development . All of the organic solvents used in the extraction were purchased from Daejung Chemical as first-class reagents. Acetonitrile, methanol and water used as HPLC solvents were HPLC grade high purity solvents of J. T Baker.

Example : Separation of the compound represented by the formula (1)

The compound 1- (2,4,6-trihydroxy-3-methylphenyl) butan-1-one represented by the formula (1) was isolated from the hot water extract of the pigments by organic solvent fractionation, silica gel column chromatography and high performance liquid chromatography And a schematic diagram of the separation process is shown in FIG.

1) Preparation of spectral extracts

50 g of the pulverized product was immersed in 1 L of water for 1 hour and then subjected to hot water extraction for 4 hours using a Daewoong extruder (DWP-5000M, Incheon, Korea). After extracting with hot water, it was concentrated under reduced pressure and lyophilized to obtain 100 g of a tube extract.

2) Fractionation of dichloromethane (CH ₂ Cl ₂ ) fractions of spectral extracts

100 g of the hot water extract prepared in Example 1-1) was suspended in 6 L of water and mixed with 6 L of dichloromethane to separate the dichloromethane-soluble layer. The above procedure was repeated five times and then concentrated under reduced pressure to obtain 1.2 g of a dichloromethane fraction (CH ₂ Cl ₂ ).

3) Isolation and structure identification of the compound represented by the formula (1)

The remaining water layer in Example 1-2) was mixed with 6 L of ethyl acetate to separate the ethyl acetate dissolved layer. This process was repeated 5 times and then concentrated under reduced pressure to obtain 3.9 g of ethyl acetate fraction (EtOAc).

4) Production of butanol fraction (BuOH) of the spectral extract

The remaining water layer in Example 1-3) was mixed with 6 L of n-butanol (normal butanol) to separate the n-butanol dissolving layer. The above procedure was repeated 5 times and then concentrated under reduced pressure to obtain 15.0 g of n-butanol fraction (BuOH).

5) Isolation and structure identification of the compound represented by the formula (1)

Silica gel column chromatography according to the polarity was carried out using 1.1 g of the dichloromethane fraction (CH ₂ Cl ₂ ) prepared in Example 2 and methanol, and 6 fractions A1 (185.9 mg) , A2 (235.4 mg), A3 (229.8 mg), A4 (256.6 mg), A5 (125.4 mg) and A6 (140.1 mg). It was confirmed by HPLC and TLC that the A2 fraction contained the active ingredient. Thus, fraction A2 (235.4 mg) was subjected to silica gel column chromatography (CH ₂ Cl ₂ : MeOH = 40: 1) (35.8 mg), B2 (115.0 mg), B3 (36.7 mg) and B4 (22.1 mg) were obtained by fractionation of fractions having similar fluorescence according to the method described in Example 1. Fraction B2 (115.0 mg) (CH ₂ Cl ₂ : MeOH = 10: 1) to obtain 76.1 mg of compound fraction C1 and 34.6 mg of C2. The fraction B3 (36.7 mg) and C1 (76.1 mg) were subjected to preparative RP-HPLC (HwO: ACN = 30: 70) to give 44.3 mg of a red amorphous solid .

[Chemical Formula 1]

API-MS: m / z = 209.2 [MH] ^- ;

¹ H NMR (400 MHz, MeOD)? 5.87 (1H, s, H-5), 1.90 (3H, s, H-7), 3.01 (2H, t, J = 7.6 Hz, 2H, m, H-10), 0.96 (3H, t, J = 7.6 Hz, H-11);

^{13 C NMR (100 MHz, MeOD} ) δ 103.6 (C-1), 161.4 (C-2), 105.2 (C-3), 162.7 (C-4), 94.8 (C-5), 165.1 (C-6 ), 7.4 (C-7), 207.4 (C-8), 46.9 (C-9), 19.6 (C-10), 14.4 (C-11).

The compound of the present invention represented by the above formula (1) was a red amorphous solid compound having an m / z = 209.2 [MH] ^- peak in API-MS, and the molecular formula was C ₁₁ H ₁₄ O ₄ . Two methyl groups were identified through a peak of delta 1.90 (3H, s), 0.96 (3H, t) in the ¹ H NMR spectrum and two methylene groups were detected through the delta 3.01 (2H, t) Respectively. A total of 11 carbons were identified in the ¹³ C NMR spectrum. One benzene ring was identified at δ 164.9, 163.7, 161.4, 105.2, 103.6 and 94.8 peaks and one carbonyl group at δ 207.4 peak was identified as δ 14.4, Two methyl groups were identified at the 7.4 peak. Thus, it was confirmed that the compound represented by Formula 1 was 1- (2,4,6-trihydroxy-3-methylphenyl) butan-1-one.

Experimental Example : Platelet cell Cohesion  Analysis of inhibition effect

In order to confirm the effect of Compound 1- (2,4,6-trihydroxy-3-methylphenyl) butan-1-one (Compound 1) isolated in Example 3 above on thrombosis, platelets were collected from an animal model, (Chrono-Log Co., Havortown, Pa., USA) according to the turbidimetry method (Born GV, Cross MJ. Aggregation of blood platelets, J. Physiol 168: 178-95, Was used to analyze the inhibitory effect of platelet aggregation.

First, platelets were collected from animal models. Male rabbits (Newzealand white rabbit: Sam-Tako Animal Co., Osan, Korea) were bred sufficiently to be able to ingest water and feed at 24 ° C and 55% relative humidity. Blood was collected from the ear artery of the rabbit and an anticoagulant citrate dextrose (citric acid 0.8%, trisodium citrate 2.2%, dextrose 2% (w / v) / v)) containing the above-obtained blood. The platelet rich plasma (PRP) was then centrifuged at 230 × g for 10 minutes to centrifugate the platelet rich plasma (PRP) at 800 × g for 15 minutes to precipitate the platelets . The precipitated platelets 0.35% SA and 0.4 mM EGTA (ethylene glycol bis (β- aminoethyl ether) - N, N, N ' , N' (N ') - tetraacetic acid) Hepes buffer (137 mM NaCl containing , 2.7 mM KCl, 1 mM MgCl2, 5.6 mM glucose and 3.8 mM Hepes, pH 6.5). The washed platelets were suspended again in Hepes buffer (pH 7.4), adjusted to 4 x 10 ³ cells / ml and used in the experiment.

The washed platelet rich plasma was incubated at 37 ° C with stirring at 1,000 rpm in a flocculation scale. The compound 1- (2,4,6-trihydroxy-3-methylphenyl) butan-1-one (Compound 1) isolated in Example 5 above was dissolved in each of 0 μM, 10 μM, 30 μM, 50 μM or 100 μM To the culture medium. As a negative control, DMSO (dimethyl sulfoxide) was added in the same volume as the extract. As a positive control, aspirin was added to the platelet culture solution at a concentration of 0 μM, 10 μM, 30 μM, 50 μM or 100 μM, Respectively. Then, collagen (5 / / ml), arachidonic acid (100 M), or thrombin (0.1 U / ml) was added as a platelet aggregation inducing substance to the platelets Induced aggregation. The extent of aggregation of the platelets was measured using a platelet aggregation tester (Chrono-Log Co., USA), and the results are shown in FIG. 2 to FIG.

2 to 3, the compound 1- (2,4,6-trihydroxy-3-methylphenyl) butan-1-one (Comppound 1) of the present invention isolated in Example 3 above was inoculated with collagen and arachidonic acid (Fig. 2). As a result, it was confirmed that the compounds of the present invention were more effective at 50 [mu] M and 100 [mu] M than platelet aggregation caused by collagen even when compared with aspirin, . Also, in the aggregation phenomenon of platelet caused by arachidonic acid, the positive control group was compared with aspirin, and it was found that 1- (2,4,6-trihydroxy-3-methylphenyl) butan-1-one (Fig. 3).

Claims (8)

A pharmaceutical composition for preventing or treating thrombosis, which comprises a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

2. The pharmaceutical composition according to claim 1, wherein the compound represented by the formula (1) is extracted from a crowd.
The pharmaceutical composition according to claim 1, wherein the composition has platelet aggregation inhibitory activity.
2. The pharmaceutical composition according to claim 1, wherein said thrombosis comprises arteriosclerosis.
A health functional food composition for preventing or ameliorating thrombosis comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

The health functional food composition according to claim 5, wherein the compound represented by the formula (1) is extracted from the spectra.
The health functional food composition according to claim 5, wherein the composition has platelet aggregation inhibitory activity.
6. The health functional food composition according to claim 5, wherein the thrombosis comprises arteriosclerosis.

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