KR101055337B1 - Blood circulation improvement composition containing five extracts or fractions thereof as an active ingredient - Google Patents

Abstract

The present invention relates to a blood circulation improving composition containing an ume extract or a fraction thereof as an active ingredient, and more particularly, to a pharmaceutical composition for preventing and treating thrombosis disease due to blood circulation improvement containing an ume extract as an active ingredient. . The mae extract or fractions thereof according to the present invention are excellent in inhibiting whole blood platelet aggregation and blood flow adhesion induced by hematopoietic stress induced by collagen in vitro, such as atherosclerosis, cerebral hemorrhage, stroke, cerebral infarction, etc. It can be usefully used for the prevention and treatment of diseases associated with blood circulation disorders.

Ume, extract, blood circulation, thrombosis

Description

Composition for enhancing blood circulation containing the extract or fraction of Prunus Mume as an active ingredient}

The present invention relates to a blood circulation improving composition containing a mae extract or a fraction thereof as an active ingredient.

Recently, circulatory diseases such as arteriosclerosis, cerebral hemorrhage, hypertension, heart disease, stroke and cerebral infarction are the leading causes of death in Korea as well as developed countries. As the adult disease develops into a modern society, it frequently occurs in middle-aged and middle-aged people due to changes in dietary habits and internal and external environmental stresses. Vascular blockage may occur due to various causes, such as cardiovascular blockage, myocardial infarction may occur, and when blood vessels in the brain are blocked, cerebral infarction may occur. In cerebral infarction, the disease can continue and cause strokes that can lead to death. In the United States, stroke is the third leading cause of death among adults and is known to be the biggest contributor to mobility. The main cause of these diseases is known as thrombus, which is recognized as a pathology mediated by excessive platelet aggregation. In addition, this also causes a disorder of blood circulation.

Hemostasis is a mechanism to prevent bleeding from blood vessels whose original shape has been destroyed, through the complex process of platelet activation, adhesion of platelets and vascular components, and the associated coagulation factors [Harlan and Harker, Med. Clin. North. Am ., 65: 855, 1981. On the other hand, platelets are activated by stimulation of various agglomerates such as collagen, arachidonic acid, and aDP (adenosine diphosphate) during blood vessel damage, thereby adhering to adhesion and secretion. And aggregate aggregation. These reactions are associated with haemostasis and are known to be involved in the development of circulatory diseases, including thrombosis and the like.

Platelets have a characteristic discoid form at rest, but when activated, they lose their intrinsic shape and undergo an irregular shape with fictitious shapes, and polymerize cytoskeletons. , Results of phosphorylation and thus interactions (Nachmias et al., Nature , 313: 70, 1985).

Antiplatelet agents developed to date include theopylline, molsidomin, verapamil and nifedipine. They are known to inhibit the mobilization of Ca ²⁺ by promoting the production of cAMP and cGMP. Nonsteroidal compounds such as aspirin, imidazole, and indomethacin are also known as drugs having antiplatelet action by inhibiting the production of thromboxane A ₂ . However, drugs made of the chemicals have a problem of causing various side effects such as excessive hemostasis suppression, infertility, digestive disorders in the human body. Accordingly, in order to find a substance having the same effect while reducing side effects of the drug made of the chemical substance, a lot of researches on substances that improve blood circulation from natural products or herbal prescriptions have been conducted.

Catechin is mentioned as such a natural substance. Catechin, which is included in green tea, is a type of antioxidant that is known to be effective in lowering bad cholesterol and preventing blood clots. It has also been reported to improve blood vessel function after 30 minutes of drinking green tea. [European cardiovascular prevention and society Reversion Journal July 2008]. However, there is still a constant demand for improved blood circulation improvers using food and herbal extracts.

On the other hand, Prunus Mume (Pumeus Mume) is the raw fruit of plum tree, which is covered in a jar, covered with a lid, and then sutured with mud and heated until it is black. It is said to be good to use when your heart is stuffy and indigestible due to nervousness. In addition, the ume has been known to have an immune function, antibacterial action, hypoglycemic effect, the conventional research on the efficacy of maeja the inhibitory effect of the urase activity of Helicobacter Philo including mae extract (Korean Patent Publication No. 2006-0040254) And analgesic action of beta sitosterol-OD-glucose isolated from buckwheat extract (Korean Patent Publication No. 1998-0043925). However, there have been no studies on the blood circulation improvement effect of ume extract.

Therefore, while the present inventors are studying blood circulation improving agents using food and herbal extracts, the ume extract or acetate fraction and active fraction thereof have superior efficacy to inhibiting whole blood coagulation, and platelet induced by blood cell deformation stress (shear stress). The present invention has been found to be excellent in inhibiting adhesion ability.

It is an object of the present invention to provide a composition for the prevention and treatment of thrombotic diseases caused by blood circulation improvement, containing an ume extract or a fraction thereof as an active ingredient.

Another object of the present invention to provide a health functional food composition for blood circulation improvement containing the mae extract or fractions thereof as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of thrombotic diseases by blood circulation improvement containing the mae extract or fractions thereof as an active ingredient.

In addition, the present invention provides a health functional food composition for improving blood circulation, containing a mae extract or a fraction thereof as an active ingredient.

The mae extract or fractions thereof according to the present invention are excellent in inhibiting whole blood platelet aggregation and blood flow adhesion induced by hematopoietic stress induced by collagen in vitro, such as atherosclerosis, cerebral hemorrhage, stroke, cerebral infarction, etc. It can be usefully used for the prevention and treatment of diseases associated with blood circulation disorders.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.

The present invention provides a pharmaceutical composition for the prevention and treatment of thrombotic diseases caused by blood circulation improvement containing the mae extract as an active ingredient.

The ume extract is preferably obtained by extracting from the ume, which is heated, until it is black by sealing it with a lid after putting the unripe fruit of the plum tree in a jar, and cultivating it or commercially available. It can be used without limitation.

The method of preparing the mae extract may be used in the conventional extraction methods in the art, such as ultrasonic extraction, filtration and reflux extraction. Preferably, the mae may be an extract extracted with water, C ₁ ~ C ₄ alcohol or a mixed solvent thereof, more preferably may be an extract extracted by immersion in water, methanol, ethanol or a mixed solvent thereof. For example, after drying the dried umeol in an extraction container and put a lower alcohol of C ₁ ~ C ₄ or a mixed solvent thereof, preferably methanol or ethanol and leave at room temperature for a certain period of time, and then filtered to obtain an alcohol extract. have. At this time, the extraction is preferably left for 1 week at room temperature, after which it may be further subjected to a method such as concentration or lyophilization.

The present invention also provides a pharmaceutical composition for the prevention and treatment of thrombotic diseases caused by blood circulation improvement containing ethyl acetate fraction of ume as an active ingredient.

Preferably, the mae fraction may be obtained by suspending the mae extract in water and then sequentially fractionated with dichloromethane and ethyl acetate.

As an example, as shown in Figure 1 , the ethyl acetate fraction of the ume suspending the ethanol extract of the ume in water, shake the same amount of dichloromethane and fractionated three times, separated into a dichloromethane layer and a water layer, Ethyl acetate was added to the separated water layer, shaken, and fractionated three times to obtain an ethyl acetate layer and a water layer.

Furthermore, the present invention provides a pharmaceutical composition for the prevention and treatment of thrombotic diseases caused by blood circulation improvement containing the active fraction of ume as an active ingredient.

The active fraction can be obtained by performing silica gel column chromatography using ethyl acetate fraction of five solvents as a mobile phase using a mixed solvent of ethyl acetate and hexane. In this case, the silica gel column chromatography is ethyl acetate solvent concentration of 0% (ethyl acetate: hexane = 0: 100), 15% (ethyl acetate: hexane = 15: 85), 30% (ethyl acetate: hexane = 30: 70), 45% (ethyl acetate: hexane = 45: 55), 60% (ethyl acetate: hexane = 60: 40), 75% (ethyl acetate: hexane = 75: 25), 90% (ethyl acetate: hexane = 90:10) and 100% (ethyl acetate: hexane = 100: 0) using a mixed solvent of ethyl acetate and hexane to perform sufficient column chromatography on each of the eight different concentrations of the mixed solvent to obtain fractions 1 to 8 Eight fractions of were obtained, of which active fractions can be obtained from fractions 2, 3, 7 and 8.

The extract or fraction obtained through the extraction and separation method may then be concentrated, dried. The concentration method may be concentrated by a conventional method in the art, preferably concentrated under reduced pressure using a rotary vacuum concentrator. The method for preparing the powder is not particularly limited, but after adding water to the concentrated extract and freezing it, it may be dried using a lyophilizer to prepare a powder.

As a result of investigating the inhibition of whole blood aggregation using the ume extract, ethyl acetate fraction or active fraction thereof according to the present invention, it was confirmed that the whole blood aggregation inhibition rate was equal to or higher than that of the comparison group catechin (see Table 1).

In addition, in the platelet adhesion inhibitory effect experiment, it was confirmed that the blood cell adhesion is greatly reduced by administering the mae extract according to the present invention can effectively inhibit the aggregation of platelets (see Fig. 2 ).

Through this, the ume extract, ethyl acetate fraction or active fraction thereof of the present invention not only has an excellent inhibitory effect on whole blood aggregation, but also has an excellent inhibitory effect on blood cell adhesion induced by hemocytosis stress, thereby preventing thrombosis due to blood circulation improvement. And it can be usefully used as a therapeutic pharmaceutical composition.

In this case, the thrombosis disease is not particularly limited as long as it can be caused by blood clots or blood circulation problems, and may be usefully used in diseases such as arteriosclerosis, cerebral hemorrhage, cerebral hemorrhage, and cerebral infarction. .

The compositions according to the invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of diseases involving thrombus formation.

The composition according to the present invention may be prepared by including one or more pharmaceutically acceptable carriers in addition to the above-described active ingredients for administration. Pharmaceutically acceptable carriers may be used in combination with saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, if necessary, as antioxidants, buffers And other conventional additives such as bacteriostatic agents can be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Furthermore, it may be preferably formulated according to each disease or component by an appropriate method in the art or using a method disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA.

The composition according to the invention can be administered orally or parenterally (eg, applied intravenously, subcutaneously, intraperitoneally or topically) according to the desired method, and the dosage is based on the weight, age, sex, health of the patient. The range varies depending on the condition, diet, time of administration, method of administration, rate of excretion and the severity of the disease. The daily dose of the mixed extract according to the present invention is 500 ± 200 mg / kg, preferably 400 ± 100 mg / kg, preferably administered once to three times a day.

In addition, the present invention provides a dietary supplement comprising the five extract, ethyl acetate fraction or active fraction thereof.

The mae extract, ethyl acetate fraction or active fraction thereof according to the present invention can be added to a health food for the purpose of improving diseases caused by blood circulation disorders, when the extract or fraction of the present invention is used as a food additive, The mixture may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method. The blending amount of the active ingredient may be suitably determined according to the purpose of use (prevention, health or therapeutic treatment). In general, the omega of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less based on the raw material in the manufacture of food or beverage. However, in the case of long-term intake for health and hygiene purposes or health control purposes, the amount may be below the above range, and since there is no problem in terms of stability, the active ingredient may be used in an amount above the above range.

There is no particular limitation on the kind of food. Examples of foods to which the substance may be added include beverages, teas, drinks and vitamin complexes, and include all of the health functional foods in the conventional sense.

The food supplement additive of the present invention may use various flavors or natural carbohydrates. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 parts by weight, preferably 0.02 to 0.03 parts by weight per 100 parts by weight of the composition according to the present invention.

In addition to the above, the extract or fraction according to the present invention can be used in various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal concentrates, pH adjusting agents, stabilizers, preservatives, Glycerol, alcohols, carbonation agents used in carbonated drinks, and the like. In addition, the composition according to the present invention may contain fruit flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components can be used independently or in combination, and the proportion of the additive is not critical, but is usually selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition according to the present invention.

Hereinafter, the present invention will be described in more detail by the following examples and experimental examples. However, the following Examples and Experimental Examples are only illustrative of the contents of the present invention and the scope of the invention is not limited by the Examples and Experimental Examples.

Example 1 Preparation of a Plum Extract

The omae used in this experiment was purchased from the Chinese herbal medicine market (Daejeon) and used by the Korean Institute of Oriental Medicine quality test team after comparing and verifying the external form.

Dried o medium (4 kg) was added to a flask, and 95% ethanol was added thereto, followed by extraction for leaching at room temperature for 7 days. The extraction process was repeated twice, and the extract was filtered with filter paper, centrifuged at 450 × g, and the supernatant was concentrated under reduced pressure with a rotary vacuum concentrator to prepare a mae extract (yield 21%).

Example 2 Preparation of Ethyl Acetate Fraction of Plum Extract

      The ume extract (840 g) prepared in Example 1 was suspended in 3 L of distilled water, and the same amount of dichloromethane (MC) was added thereto, shaken and separated three times. The dichloromethane layer and the water layer were separated. Ethyl acetate was added to the separated water layer and the mixture was shaken and fractionated three times. The mixture was separated into an ethyl acetate layer and a water layer. Butanol was added to the separated water layer and the mixture was shaken and fractionated three times to separate the butanol layer and the water layer. From this, a dichloromethane layer fraction (54g), an ethyl acetate layer fraction (170g), butanol layer fraction (440g) and a water fraction (194g) were prepared. As a result of whole blood aggregation inhibition test, the ethyl acetate layer of the fraction showed an excellent whole blood aggregation inhibitory effect.

Example 3 Preparation of Active Fraction from Ethyl Acetate Fraction of Ome

In the ethyl acetate fraction (170 g) of Example 2, the concentration of ethyl acetate solvent was 0% (ethyl acetate: hexane = 0: 100), 15% (ethyl acetate: hexane = 15: 85), 30% (ethyl acetate: Hexane = 30: 70), 45% (ethyl acetate: hexane = 45: 55), 60% (ethyl acetate: hexane = 60: 40), 75% (ethyl acetate: hexane = 75: 25), 90% (ethyl Silica gel column chromatography (70-70) was carried out for each of eight kinds of mixed solvents using a mixed solvent of ethyl acetate and hexane, which were acetate: hexane = 90: 10) and 100% (ethyl acetate: hexane = 100: 0). 230 mesh, Merck) was used to separate into eight fractions (fractions 1-8). Among them, fraction 2 (1.1 g), fraction 3 (3.8 g), fraction 7 (1.6 g) and fraction 8 (31.5 g) showed excellent anticoagulant activity.

Experimental Example 1 Measurement of Inhibitory Effect on Whole Blood Coagulation In vitro )

In order to determine the inhibitory effect of whole blood coagulation of the mae extract of the present invention, the following experiment was performed.

Eight adults (eight women) between the ages of 20 and 30 were randomly selected and were not given aspirin or nonsteroidal anti-inflammatory drugs a week before the blood was drawn. At a given time, blood was drawn with a 5 ml disposable plastic syringe and then dispensed into a vacuum tube (vaccutainer, Becton Dickinson, USA) containing 3.2% sodium citrate anticoagulant to prevent coagulation. Then, whole blood coagulation inhibitory activity was measured using an aggregate coagulation analyzer (aggregometer, Chrono Log, USA). After diluting with physiological saline so that the platelet count of whole blood becomes 4 × 10 ⁸ cells / ml, and incubating for 10 minutes at 37 ° C., the sample suspension in which the ume extract or fractions prepared in Examples 1 to 3 was suspended in physiological saline solution was prepared. 50 µl was added and allowed to react for 5 minutes. Saline was used as a negative control group, and green tea catechin (Wako, Japan) was used as a comparative group. Subsequently, the platelet aggregation inducing agent collagen (2 μg / ml, Chrono Log, USA) was added in a certain amount and reacted at 37 ° C. while stirring at 1,000 rpm to determine the degree of whole blood aggregation as a change in impedance. At this time, the whole blood coagulation inhibitory ability to obtain the inhibition rate according to the concentration by analyzing the impedance of the whole blood aggregation, using this to obtain the concentration of the extract corresponding to the inhibition rate 50%.

The experimental results are shown in Table 1.

sample Concentration (µg / ml) Impedance % Inhibition IC ₅₀ (μg / ml) Negative Control
(Physiological saline) - 16.6 ± 4.2 - Comparison
(Green Tea Catechin) 500 6.7 ± 2.6 64.3 ± 14.7 384 250 10.9 ± 3.7 43.5 ± 15.9 125 14.0 ± 2.8 26.7 ± 9.4 Ethanol extract 2500 0.0 ± 0.0 100.0 ± 0.0 515 1250 0.5 ± 0.7 96.7 ± 4.7 500 5.6 ± 2.3 61.2 ± 29.4 250 9.5 ± 4.9 22.9 ± 12.2 Ethyl acetate layer
Fraction 2500 0.0 ± 0.0 100.0 ± 0.0 214 1250 1.0 ± 1.2 94.7 ± 6.1 500 3.6 ± 2.1 80.0 ± 12.2 250 5.0 ± 1.2 62.6 ± 14.3 125 14.0 ± 4.7 25.4 ± 6.5 Butanol layer
Fraction 2500 0.0 ± 0.0 100.0 ± 0.0 684 1250 4.3 ± 3.6 78.6 ± 18.7 500 8.8 ± 2.3 45.8 ± 14.5 125 13.0 ± 2.4 31.4 ± 14.3 50 18.0 ± 4.9 5.6 ± 1.5 Water layer 2500 0.0 ± 0.0 100.0 ± 0.0 506 1250 0.8 ± 1.5 94.6 ± 10.7 500 6.8 ± 3.6 62.6 ± 17.5 125 14.0 ± 0.6 33.5 ± 5.0 62.5 15.0 ± 6.6 24.7 ± 25.1 50 18.0 ± 4.9 10.9 ± 20.1 Fraction 1 500 15.5 ± 2.12 13.9 ± 11.8 - Fraction 2 500 1.6 ± 1.0 92.3 ± 3.7 101 250 3.7 ± 2.6 79.2 ± 14.5 125 5.0 ± 0.0 73.9 ± 4.7 50 12.3 ± 6.4 37.6 ± 17.9 Fraction 3 500 2.0 ± 2.8 90.0 ± 12.0 162 250 5.7 ± 1.2 70.2 ± 6.1 125 10.0 ± 0.0 39.3 ± 2.6 Fraction 4 500 4.8 ± 2.3 65.8 ± 20.3 - Fraction 7 500 0.6 ± 0.6 96.2 ± 3.5 303 250 10.0 ± 1.41 37.5 ± 8.8 Fraction 8 500 1.0 ± 1.1 94.3 ± 5.4 201 250 6.7 ± 2.3 62.3 ± 14.3 125 7.5 ± 2.1 35.2 ± 14.5

As shown in Table 1, the whole blood aggregation inhibition rate of the ume extract according to the present invention represented 61.2 ± 29.4% at 500 μg / ml of ethanol extract, thereby inhibiting 64.3 ± 14.7% of the green tea catechin at 500 μg / ml. Inhibition of whole blood aggregation equivalent to). In addition, the ethyl acetate layer fraction exhibited a concentration (IC ₅₀ ) value of 214 mg / ml that inhibits human whole blood aggregation ( ₅₀ mg), which was lower than that of the comparative group (384 mg / ml). Furthermore, fractions 2, 3, 7, and 8 separated from the ethyl acetate layer showed IC ₅₀ values of 101-303 mg / ml, indicating a lower inhibitory concentration than the comparative group (384 mg / ml), especially In the case of IC ₅₀ value of 101 mg / ㎖ showed that the inhibition rate of whole human blood aggregation than the green tea catechin of the comparison group. Therefore, the mae extract or fraction according to the present invention can effectively inhibit whole blood aggregation even at low concentrations and can be usefully used for improving blood circulation.

Experimental Example 2 Measurement of Platelet Adhesion Inhibition In vitro )

In order to determine the inhibitory effect of platelet adhesion induced by hemocytosis stress of the mae extract according to the present invention, the following experiment was performed.

In order to measure platelet adhesion induced by hemodynamic stress, a blood flow chamber (live cell, Chamlide SC, Shear stress chamber) and a syringe pump (syringe pump, Harvard, KGS-101) were used. A focus microscope (Confocal laser scanning microscope, Leica, TCSSP2) was used. Only physiological saline was added to 2 ml of human whole blood as a control, and the final concentration of catechin was added to be 2.5 mg / ml as a comparative group, and the final concentration of the ethanol extract of maemae prepared from Example 1 was added to 2.5 mg / ml. It was made to react at room temperature for 5 minutes. The mixture was connected to a blood flow chamber tube containing a collagen coated slide and then the flow rate of the syringe pump was adjusted to 0.428 ml / min to allow 6 minutes to pass. This resulted in a blood cell strain stress rate of 1300 s ⁻¹ for whole blood passing through the blood flow chamber tube. After the reaction was completed, blood cells remaining on the collagen coated slides were washed by passing the thyroid buffer at the same flow rate. Images of the cells attached to the collagen-coated slides in the blood flow chamber were photographed with a CCD camera to visually determine the degree of inhibition of platelet adhesion induced by hemocytosis stress. The result is shown in Fig.

As shown in Figure 2 , the sample treated with the extract of Example 1 was found to significantly reduce blood cell adhesion than the comparison group. Therefore, the extract according to the present invention can effectively inhibit the aggregation of platelets and can be usefully used for improving blood circulation.

On the other hand, the mae extract or fractions according to the invention can be formulated in various forms according to the purpose. The following are some examples of formulation methods containing the mae extract or fraction according to the present invention as an active ingredient, but the present invention is not limited thereto.

Preparation Example 1 Preparation of Pharmaceutical Formulation

1. Preparation of powder

2 g of ume extract or ethyl acetate fraction thereof

2 g lactose

1 part by weight of starch

After mixing the above components, the airtight cloth was filled to prepare a powder.

2. Preparation of Tablets

100 mg of ume extract or ethyl acetate fraction thereof

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the usual ingredients, tablets were prepared by tableting according to a conventional method for producing tablets.

3. Preparation of Capsule

100 mg of ume extract or ethyl acetate fraction thereof

100 mg corn starch

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.

Preparation Example 2 Preparation of Beverage

1. Preparation of Carbonated Drinks

5 to 10 parts by weight of sugar, 0.05 to 0.3 part by weight of citric acid, 0.005 to 0.02 part by weight of caramel, and 0.1 to 1 part by weight of vitamin C are mixed, and the mae extract according to the present invention or the ethyl acetate fraction thereof 79 to 94 weight Mix the parts to make a syrup, sterilize the syrup for 20 to 180 seconds at 85 ~ 98 ℃ mixed with cooling water in a ratio of 1: 4 and then inject 0.5 ~ 0.82 parts by weight of carbon dioxide gas containing a carbonated beverage containing the composition of the present invention Was prepared.

2. Manufacture of health drinks

Substances such as liquid fructose (0.5 parts by weight), oligosaccharides (2 parts by weight), sugar (2 parts by weight), salt (0.5 parts by weight), water (75 parts by weight) and omega extracts according to the present invention or ethyl acetate fractions thereof 79-90 parts by weight of the homogeneous formulation was instantaneous sterilization and then packaged in a small packaging container such as glass bottles, plastic bottles to prepare a healthy beverage.

1 is a view showing a process for separating the mae extract or fractions thereof according to the present invention.

Figure 2 is a photograph showing the platelet adhesion inhibitory effect of the mae extract according to an embodiment of the present invention.

Claims (9)

delete delete The oil extract obtained by suspending the oil extract with water, methanol, ethanol, or a mixed solvent thereof in water, and then sequentially dividing with dichloromethane and ethyl acetate was used as a mobile solvent. A pharmaceutical composition for the prevention and treatment of thrombotic diseases caused by blood circulation improvement, which contains an active fraction of five medium obtained by silica gel column chromatography as an active ingredient, wherein the silica gel column chromatography has a concentration of 15% ethyl acetate solvent ( Ethyl acetate: hexane = 15: 85) pharmaceutical composition for the prevention and treatment of thrombotic diseases caused by improved blood circulation, characterized in that it is carried out using a mixed solvent of ethyl acetate and hexane. delete The pharmaceutical composition for preventing and treating thrombosis disease according to claim 3, wherein the thrombosis disease is selected from the group consisting of atherosclerosis, cerebral hemorrhage, stroke and cerebral infarction. delete delete The oil extract obtained by suspending the oil extract with water, methanol, ethanol, or a mixed solvent thereof in water, and then sequentially dividing with dichloromethane and ethyl acetate was used as a mobile solvent. A health functional food composition for improving blood circulation, which contains an active fraction of a ume obtained by silica gel column chromatography as an active ingredient, wherein the silica gel column chromatography has a concentration of 15% ethyl acetate (ethyl acetate: hexane = 15: 85) is a blood circulation improving health functional food composition, characterized in that it is carried out using a mixed solvent of ethyl acetate and hexane. delete

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