KR101536211B1 - Composition for prevention or treatment of thrombotic diseases comprising extracts or fractions of Playtcodon grandiflorum - Google Patents

Abstract

The present invention relates to a pharmaceutical composition or food composition for the prevention, treatment or amelioration of a thrombotic disease comprising Ganoderma lucidum extract or a fraction thereof as an active ingredient.

Description

TECHNICAL FIELD The present invention relates to a composition for prevention or treatment of a thrombotic disease comprising extracts of Gakyunggye or fractions thereof,

The present invention relates to a pharmaceutical composition or food composition for the prevention, treatment or amelioration of a thrombotic disease comprising Ganoderma lucidum extract or a fraction thereof as an active ingredient.

Cardiovascular and cerebrovascular diseases are the most common adult diseases that are the second or third cause of death. Especially, cardiovascular diseases include heart diseases, central blood vessels and peripheral blood vessel diseases, and there are mutual interactions among the various diseases, and they may develop into other disease groups according to the progress of the disease. Drug therapy and surgical treatment are used simultaneously for the treatment of cardiovascular diseases, but drugs are the main treatment methods for heart failure, hypertension, hyperlipidemia, coronary artery disease, arrhythmia or thrombosis. According to IMS Health, the market for cardiovascular disease drugs accounted for about one-fifth of the market for all types of drugs in 2002. With the aging society, the cardiovascular disease drug market is expected to grow steadily.

Because thrombus plays a central role in the development and progression of circulatory disease, prevention of thrombus formation and effective removal of the generated thrombus are important in the treatment of vascular disease. Thrombosis is a pathological response to a normal haemostasis, which can occur when platelet aggregation and plasma coagulation are over activated. Prevention and treatment of thrombotic diseases Drugs are largely classified as thrombolytic agents, anticoagulants and antiplatelet agents. Anticoagulants such as heparin and coumarin, which inhibit blood clotting by inhibiting blood clotting, and thrombolytic agents that dissolve fibrin, which is a major constituent of thrombus, to dissolve thrombus already formed are used for the first aid treatment of thrombotic diseases. However, It is not suitable for long-term treatment because of side effects such as hemorrhage at the site or systemic hemorrhage.

It is known that antiplatelet agents are effective for prevention of double thrombosis. The platelets are discotic hemocyte cells with a diameter of about 2 to 4 ㎛. The platelets are hematopoietic cells, hemostasis, blood clotting, and coagulation by blood coagulation factors during the breakage of blood vessels. And a biological defibrillator for preventing the body. However, adhesion, aggregation and release of platelets by platelet activation in the occluded blood vessels cause thrombus formation and cause various thrombotic diseases. It has also been shown that micro-thromboses generated by the abnormal activation of platelets are involved not only in various thrombotic diseases but also in the expression of adult diseases such as arteriosclerosis, hypertension and diabetes, and by thrombosis released by platelet-releasing reaction, serotonin It is followed by swelling or inflammation. Therefore, anti-platelet substances having a platelet aggregation-inhibiting action have application value to prevent recurrence of serious thrombosis such as myocardial infarction and stroke, and to treat and prevent various thrombotic diseases.

Antiplatelet agents currently in use include nonsteroidal antiinflammatory drugs such as aspirin and indomethacin, which inhibit prostaglandin metabolism and reduce the production of thromboxane and reduce the amount of cAMP in platelets. In particular, aspirin is a drug that inhibits the synthesis of thromboxane A2 by irreversibly acetylating cyclooxygenase, which synthesizes prostaglandins, a platelet aggregation inducer, from arachidonic acid in cell membranes. Since the platelets do not have the ability to synthesize proteins, the platelet aggregation inhibition effect is retained until the new platelets have appeared, and the period of time is about 10 days. In fact, hospital prescriptions for the prevention of thrombosis, aspirin 100 mg per day and blood clotting preventive agent to take 2 mg of warfarin. However, in most clinical trials, aspirin therapy is associated with gastrointestinal side effects. In patients receiving aspirin, 5.2 to 40% showed symptoms such as heartburn, indigestion, nausea or vomiting, and 0.7 to 34% in the control group. In addition, the incidence of gastric ulcers in aspirin-treated groups was more than two-fold higher, affecting renal toxicity and hemorrhagic stroke, and also interacting with angiotensin-converting enzyme inhibitors The development of antiplatelet agents derived from natural materials that can replace the side effects of aspirin is of paramount importance (Alan D. Michelson, MD, Platelets, Academic Press, Elsevier Science, USA, 2002).

On the other hand, Platycodon grandiflorum is a medicinal substance made by removing the roots or juniors of Platycodon grandiflorum A. De Candolle, and its name is Gakgye because its root is hard and straight. Gyungyung works on the lungs to treat symptoms with a lot of seawater and sputum, uncomfortable breathing, clearing the lungs, releasing the stiff chest, releasing cold air in the stomach, stopping the cough and removing the wall. Also, it is used for the cases of sore throat, cold cough, sputum, nasal congestion, asthma, bronchial inflammation, pleurisy, headache, chills and tonsillitis. Studies have been carried out on phagocytosis, hypoglycemic action and improving bacteria inhibition by pharmacological action, but no studies have been reported on the prevention, treatment or improvement of thrombotic diseases of Gakyung Extract or its fractions.

Accordingly, the present inventors have made intensive efforts to develop therapeutic agents for thrombotic diseases derived from natural products, and as a result, it has been found that Gakyung extract or its fractions have an activity of inhibiting platelet aggregation, and thus can be useful for prevention or treatment of thrombotic diseases And completed the present invention.

One object of the present invention is to provide a method, graniflorum extract or fractions thereof as an active ingredient for the prevention or treatment of thrombotic diseases.

Another object of the present invention is to provide a food composition for prevention or amelioration of a thrombotic disease which contains Ganoderma lucidum extract or a fraction thereof as an active ingredient.

In order to achieve the above object, the present invention gilgyeong (Playtcodon graniflorum extract or a fraction thereof as an active ingredient. The present invention also provides a pharmaceutical composition for preventing or treating a thrombotic disease.

The term " Playtcodon " grandiflorum "is a species of Platycodon grandiflorum A. De Candolle). Although it has been known that the above-mentioned ginseng has pharmacological activity, it has a germane action, a hypoglycemic action, an action to inhibit the improvement of gynecological condition, etc. However, the therapeutic use of Gyungyang Extract or its fraction for treating thrombotic diseases is not known, It was first identified. In the present invention, Gakyung can be purchased commercially, sold or cultivated in nature.

The term "ginseng extract" used in the present invention means an extract obtained by extracting ginseng. Specifically, the extract of Ganoderma lucidum may be extracted with water, C _{1 -4} alcohol or a mixed solvent thereof, preferably extract of Ganoderma lucidum with ethanol. That is, the pulverized product is pulverized to a volume of about 2 to 20 times, preferably about 3 to 5 times the dry weight of water, a polar solvent of C _{1 -4} alcohol such as methanol, ethanol, and butanol, 0.1 to 1: 10 as an elution solvent, and the extraction temperature is 20 to 100 DEG C, preferably room temperature, and the extraction period is about 1 to 4 days. Extraction, or ultrasonic extraction. However, any method can be used without limitation as long as it is a method for extracting a substance having a prophylactic or therapeutic activity for a thrombotic disease. Preferably, the extract is continuously extracted one to five times by cold extraction, filtered under reduced pressure, and the filtrate is concentrated under reduced pressure at 20 to 100 ° C, preferably room temperature, in a vacuum rotary condenser to obtain water, C _{1 -4} alcohol But the present invention is not limited thereto. The diluent, concentrate or extract of the extract, the extract, or the extract may be dried , Or a preparation or a purified product thereof. The ginseng extract can be extracted from various organs of natural, hybrid, and variant plants and extracted from plant tissue cultures as well as roots, shoots, stems, and leaves. In one embodiment of the present invention, the milled product of gypsum diameter was immersed in ethanol for 1 hour and then extracted for 3 hours using a reflux condenser equipped with a condenser (Example 1-2).

The term "fraction " as used herein refers to the product obtained by a fractionation method for separating a specific component or a specific group from a mixture containing various constituents. Specifically, the gingivalfumarate fraction can be obtained by fractionating the ethanol extract of Gamgyeong using water, hexane, ethyl acetate, or a mixed solvent thereof. Preferably, the ethanol extract of Gamgyeong is fractionated with ethyl acetate. That is, in the case of the ginseng fractions of the present invention, the ginseng extract is suspended in water and then fractionated using a solvent such as hexane or ethyl acetate to obtain a polar solvent fraction and a non-polar solvent fraction, respectively. Specifically, the ethanol extract of Gamgyeong is suspended in distilled water, and a nonpolar solvent such as hexane or ethyl acetate at about 1 to 10 times, preferably about 1 to 5 times the volume of the suspension is added to the suspension for 1 to 10 times Can be obtained by extracting and separating the non-polar solvent soluble layer two to five times. Further, a conventional fractionation process may be performed (Harborne JB Plant Pathology, 1998, 3rd Ed. P6-7). More specifically, after suspending the ethanol extract of gilmania in water, ethyl acetate may be added to obtain an ethyl acetate-soluble fraction and a water-soluble fraction. In one embodiment of the present invention, the Ganoderma ethanol extract was suspended in water to obtain an ethyl acetate fraction, and then the butanol fraction was obtained by adding butanol to the remaining water-soluble fraction (Examples 1-3 and 1-4).

The extract of Ganoderma lucidum or its fractions of the present invention can be effectively used for the prevention or treatment of thrombotic diseases.

The term " thrombotic disease " used in the present invention means all diseases caused by thrombosis, and in particular, refers to any disease caused by clogging of blood vessels due to thrombosis. As the cause of the disease, it is known that factors such as slow blood flow, excessive coagulation, vascular damage, etc. act alone or in combination, but it is not limited thereto. The thrombotic diseases include thrombosis, hypertension, stroke, cerebral infarction, angina pectoris, myocardial infarction, arteriosclerosis, peripheral arterial occlusion, renal vein occlusion, central retinal vein occlusion, pulmonary thrombosis, deep vein thrombosis, portal vein thrombosis, cerebral sinus thrombosis, Atherosclerosis, ischemic heart disease, or ischemic heart disease caused by thrombosis and platelet aggregation, preferably from the group consisting of hypertension, hypertension, stroke, cerebral infarction, angina pectoris, myocardial infarction, arteriosclerosis or ischemic heart disease. But is not limited thereto.

The term "prophylactic " as used in the present invention means any action that inhibits or delays the thrombotic disease by the platelet aggregation inhibiting activity in the composition. As used herein, the term "treatment" refers to any action that alleviates or alleviates symptoms due to thrombotic diseases due to platelet aggregation inhibitory activity in the composition.

The pharmaceutical composition comprising the extract of Ganoderma lucidum or a fraction thereof of the present invention may further comprise an appropriate carrier, adduct or diluent conventionally used in the production of a pharmaceutical composition. At this time, the content of Ganoderma lucidum extract or its fraction contained in the composition is not particularly limited, but it may include 0.001 wt% to 20 wt%, preferably 0.01 wt% to 10 wt%, based on the total weight of the composition .

The pharmaceutical composition may be in the form of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, And may be oral or parenteral formulations of various types. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

The composition of the present invention may be administered in a pharmaceutically effective amount.

The term " pharmaceutically effective amount " as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and the effective dose level will vary depending on the species and severity, age, The type of disease, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art. The preferred dosage of the composition of the present invention depends on the condition and the weight of the patient, the degree of the disease, the type of the drug, the administration route and the period, and the administration may be carried out once a day or divided into several times. The composition is not particularly limited as long as it is an object for the treatment of a thrombotic disease, and any composition can be applied. For example, any non-human animal such as a monkey, a dog, a cat, a rabbit, a guinea pig, a rat, a mouse, a cattle, a sheep, a pig or a goat can be used. Including, without limitation, methods. For example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.

In one embodiment of the present invention, it was confirmed that the ethanol extract inhibits the platelet aggregation inhibition activity much more than the hot water extract of Gilbang (Fig. 1). In addition, it was confirmed that the ethyl acetate fraction of the ethanol extract had a greater platelet aggregation activity than the butanol fraction containing a large amount of saponin (FIG. 2). Therefore, the extract of Ganoderma lucidum or a fraction thereof of the present invention can be usefully used for the prevention or treatment of thrombotic diseases.

The present invention also provides a food composition for preventing or ameliorating a thrombotic disease comprising Ganoderma lucidum extract or a fraction thereof as an active ingredient.

The above extracts, fractions, and thrombotic diseases are as described above.

As used herein, the term "improvement" refers to the use of a composition comprising an extract of Ganoderma lucidum or a fraction thereof as an active ingredient to improve suspicion of thrombotic diseases prevented or treated by platelet aggregation inhibitory activity, All activities that

Specifically, the extract of the present invention or a fraction thereof may be incorporated into a food composition for the purpose of preventing or improving a thrombotic disease.

The kind of the food of the present invention is not particularly limited. Examples of the food to which the ginseng extract or its fractions can be added include meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen noodle, other noodles, dairy products including gums, ice cream, Tea, a drink, an alcoholic beverage, and a vitamin complex, and can include foods in a conventional sense, and foods used as feed for animals.

In addition to the above, the food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, , A carbonating agent used in carbonated drinks, and the like. It may also contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. The food may also be prepared in the form of tablets, granules, powders, capsules, solutions in liquid form, and the like according to known production methods. In addition, various conventional flavors or natural carbohydrates may be included as additional components.

When the extract or its fractions of the present invention are used as a food additive, the extract or the fraction thereof may be used as it is or may be used together with other foods or ingredients, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use. The food additives are intended to improve the appearance, flavor, texture, or shelf life and are intended to be added intentionally to food. The quality of the food is improved to improve preservability or palatability, It is meant to be used for the purpose of promoting value. This may be a substance used in food production, processing, or preservation, as defined in Article 2 (2) of the Food Sanitation Act, by addition to food, mixing, infiltration, or other methods.

Since the extract of Ganoderma lucidum or its fractions of the present invention is derived from a natural product that has been used for a long time as a natural medicinal material and has no side effects and has platelet aggregation inhibiting activity, the composition of the present invention comprising the extract of Ganoderma lucidum or a fraction thereof, Prevention, treatment, or amelioration.

FIG. 1 is a graph showing the results of (A) inhibitory effect on platelet aggregation induced by collagen of hydrothermal / ethanol extract of Gil-Kyung and (B) analysis of inhibitory effect on platelet aggregation according to concentration of ethanol extract of Gil-Kyunggi.
FIG. 2 is a graph showing the results of analysis of (A) inhibitory effect of platelet aggregation induced by platelet aggregation of collagen and arachidonic acid in (B) Gilchyung ethyl acetate fraction.
FIG. 3 is a graph showing the results of the inhibitory effect of phosphorylation activity of PLCγ2, AKT and p47 increased by collagen of the ethyl acetate fraction of Gil-Kyung.

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.

Example  One: Gakyung  Extract and its Fraction  Produce

Example  1-1: Gakyung Of hot-water extract  Produce

Fifty grams of the Gyungyang pulverized product was immersed in 1 liter of water for 1 hour and then subjected to hot water extraction for 4 hours using Daewoong Extractor (DWP-5000M, Incheon, Korea). After hot water extraction, it was concentrated under reduced pressure and lyophilized to obtain 100 g of Gakyung hot-water extract.

Example  1-2: Gakyung  Preparation of ethanol extract

50 g of the ground powder was added to 1 L of ethanol and immersed for 1 hour, followed by extraction using a reflux condenser equipped with a condenser for 3 hours. The mixture was extracted with ethanol, concentrated under reduced pressure, and lyophilized to obtain 100 g of an ethanol extract of Guryeong.

Example  1-3: Gakyung  The ethyl acetate of the extract ( EtOAc ) Fraction  Produce

100 g of the Ganoderma lucidum ethanol extract prepared according to Example 1-2 was suspended in 2 L of water and then 2 L of ethyl acetate (EtOAc) was mixed to separate the ethyl acetate dissolution layer. This procedure was repeated 5 times and then concentrated under reduced pressure to obtain 10.4 g of ethyl acetate fraction.

Example  1-4: Gakyung  Extract Butanol ( BuOH ) Fraction  Produce

After the fractionation of Example 1-3, the remaining water layer was mixed with 2 L of n-butanol (normal butanol) to separate the n-butanol dissolving layer. The above procedure was repeated five times and then concentrated under reduced pressure to obtain 10.7 g of n-butanol fraction (BuOH).

Experimental Example  One: Gakyung  The extract and Fraction  Platelet cell Cohesion  Analysis of inhibition effect

Platelets were collected from an animal model and analyzed by the turbidimetry method (Born GV, Cross MJ., Aggregation of blood platelets, J) to determine the effect of Ganoderma lucidum extract and its fractions prepared in the above examples on thrombosis. (Chrono-Log Co., Havortown, Pa., USA) was used to analyze the inhibitory effect of platelet aggregation on platelet aggregation according to the method described in J. Physiol 168: 178-95, 1963. E20-ethanol (ethanol extract), E20-BuOH (butanol fraction) and E20-EA (ethylacetate fraction) were named as G20 extracts or fractions.

First, platelets were collected from animal models. Male rabbits (New Zealand white rabbit: Sam-Tako Animal Co., Osan, Korea) were fed at a temperature of 24 ° C and relative humidity of 55% to feed water and feed freely. 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% (v / v) w / v)). 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 . Precipitated platelets were incubated in Hepes buffer (137 mM NaCl (pH 7.4)) containing 0.35% SA and 0.4 mM EGTA (ethylene glycol bis (? - aminoethyl ether) -N, N, N ', N' (N ') - tetraacetic acid) , it was washed with _{2.7 mM KCl, 1 mM MgCl 2} , 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 ⁸ cells / ml, and used in the experiment.

The washed platelet rich plasma was incubated at 37 ° C with stirring at 1,000 rpm on a flocculation scale. (E20-EA and E20-BuOH) of the extracts of Gil-Gyung hot-water extract (W20), Gakgyeong ethanol extract (E20) and Gakgyeong ethanol extract prepared in the above examples were respectively administered at 50 μg / ml, 100 μg / Ml or 500 [mu] g / ml, to the platelet culture solution. As a control, distilled water or dimethyl sulfoxide (DMSO) was added in the same volume as the extract. Thereafter, the cells were incubated for 3 minutes with stirring at 1,000 rpm at 37 DEG C, and platelet aggregation was induced by adding collagen (5 mu g / ml) or arachidonic acid (100 mu M) as platelet aggregation inducers. The extent of aggregation of the platelets was measured using an aggregometer (Chrono-Log Co., USA), and the results are shown in FIGS. 1 and 2.

As a result, Gwangyang Ethanol extract showed better platelet inhibitory activity and concentration-dependent inhibitory effect than hot-water extract (Fig. 1), while Gwangyang butanol fraction containing a large amount of saponin showed platelet aggregation inducing effect, while ethyl saponin- Acetate fraction exhibited an excellent inhibitory effect on platelet aggregation induced by collagen and arachidonic acid in a concentration-dependent manner (Fig. 2).

Experimental Example  2: Western Blot  analysis

In order to test the antiplatelet activity of the Gakyung ethyl acetate fraction, the inhibitory activity of PLCγ2, AKT and p47 on phosphorylation was measured. The phosphorylation inhibiting activity of PLCγ2, AKT or p47 as a kind of mechanism of antiplatelet action is well known in the art.

Protein extraction buffer (50 mM Tris-HCl pH 8.0, 5 mM EDTA, 150 mM NaCl, 1% NP-40, 0.1% SDS, 1 mM PMSF and one protease inhibitor cocktail tablet (Roche, Germany) The protein extracts were obtained by centrifugation (10,000 × g, 15 min, 4 ° C.) after extracting the proteins in the cells. Protein concentrations were quantified using a BCA protein assay kit (Pierce, Ill.). 10 μg protein samples were mixed with sample buffer for SDS-PAGE (100 mM Tris-HCl, 2% SDS, 1% 2-mercaptoethanol, 2% glycerol, 0.01% Bromophenol Blue, pH 7.6) Deg.] C for 5 minutes), and electrophoresed on a 10% polyacrylamide gel. Mini-protean 3 Cell (Bio-Rad, CA) was used for electrophoresis. The separated proteins in the gel were transferred to a nitrocellulose membrane (Whatman, Germany), and protein transfer and the amount of protein were determined by Ponceau S staining. After this, the nitrocellulose membrane was blocked with blocking buffer (10 mM Tris-HCl, pH 7.5, 150 mM NaCl, 0.1% Tween 20, 3% nonfat dry milk) and incubated for 2 hours with primary antibody (dilution, 1: 1000; Cell Signaling Technology, Inc., MA). At this time, the primary antibody used was an antibody (Cell Signaling Technology, Inc., MA) specifically binding to PLCγ2, AKT, and p47, which is activated by collagen and known to participate in platelet activation signal. The membrane reacted with the primary antibody was washed with blocking buffer 3 times for 10 minutes and incubated with the secondary antibody (1: 2000) for 1 hour. After washing for 10 minutes with blocking buffer, the cells were developed with SuperSignal West Femto Maximum Sensitivity Substrate (Pierce, IL). The fluorescence signal was detected using a LAS-3000 luminescence image analyzer (Fuji Photo Film Co., Japan) and the band density was measured using Multi Gauge software version 3.0 (Fuji Photo Film Co.).

As a result, the phosphorylation activity of PLCγ2, AKT and p47 was increased by the collagen in the control group not treated with the Gakyung ethyl acetate fraction. On the other hand, when Gakyung's ethyl acetate fraction was treated, the phosphorylation activity of PLCγ2, AKT and p47 was significantly decreased depending on the concentration of the fraction (FIG. 3). This suggests that Gakyung's ethyl acetate fraction has anti-platelet (platelet aggregation inhibiting) activity.

Claims (12)

Prevention or treatment of thrombotic diseases selected from the group consisting of hypertension, angina pectoris, thrombosis, myocardial infarction, and arteriosclerosis, containing the ethyl acetate fraction obtained by fractionating the ethanol extract of Playtcodon grandiflorum with ethyl acetate as an active ingredient A pharmaceutical composition.
delete delete delete delete delete A food composition for preventing or ameliorating a thrombotic disease selected from the group consisting of hypertension, angina pectoris, thrombosis, myocardial infarction, and arteriosclerosis, which comprises the ethyl acetate fraction obtained by fractionating the Ganoderma lucidum ethanol extract as an active ingredient. delete delete delete delete delete

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