WO2015108332A1 - Composition for preventing and treating cardiovascular disease - Google Patents

Abstract

The present invention relates to a composition containing a Quercus salicina extract for preventing and treating cardiovascular disease. Specifically, the Quercus salicina extract strongly activates endothelial type nitric oxide synthetase, which is a main factor of vascular protection together with antioxidative efficacy, and controls contraction and relaxation of vascular smooth muscle, thereby exhibiting a strong vascular relaxation effect, resulting in regulating blood pressure and improving vascular endothelial dysfunction, and thus the composition containing the same as an active ingredient can be favorably used as a pharmaceutical composition or functional health food for preventing and treating cardiovascular disease including endothelial dysfunction.

Description

Composition for prevention and treatment of cardiovascular disease

The present invention relates to a pharmaceutical composition for the prevention and treatment of cardiovascular diseases and health functional foods, including the extract from the participating Si, specifically inhibits oxidative stress and at the same time activates vascular endothelial nitric oxide synthase The present invention relates to a composition comprising the extract of the leaves as an active ingredient against participating trees having the effect of treating and preventing vascular endothelial dysfunction and related cardiovascular diseases by controlling the contraction and relaxation of the vascular endothelial dysfunction.

According to the statistics of the World Health Organization (WHO), in 2011, the global mortality rate of cardiovascular disease is more than 30%, and the number one disease in the world, especially in Asia such as Japan and Korea. This may be due to an increase in risk factors for coronary artery disease due to changes in aging society and dietary habits.

Endothelial dysfunction has been associated with hypertension, arteriosclerosis, and the like since non-ideal vascular relaxation was found in patients with hypertension in 1990 (Panza JA et al. , New England Journal of Medecine, 323: 22-27, 1990). It is a major dysfunctional disorder that further augments very comprehensive cardiovascular diseases such as hyperlipidemia, diabetes and obesity. (Brunner H. et al. , J. Hypertens, 2005, 23: 233-246). Vascular endothelial cells are epithelial cells lining the cavity of the heart, blood vessels and lymphatic vessels. The main function is to produce vasodilator and vasoconstrictor mediators to regulate both vascular tone and structure.

Cardiovascular diseases, including certain symptoms, including vascular endothelial dysfunction, have conventionally caused abnormalities of the heart and vascular system, arteriosclerosis, hypertension, hyperlipidemia, coronary artery disease (heart failure), cerebrovascular diseases (stroke, dementia) Names of abnormalities in the heart and blood vessels, including but not limited to, peripheral vascular disease, arrhythmia, heart failure, congestive heart disease, myocardial disease, and the like.

Genetic factors, lifestyle, and complications of diabetes mellitus are widely known as major factors in cardiovascular disease expression, but from the viewpoint of modern medicine, endothelial type Nitric Oxide Synthase (eNOS) activity is caused by decreased activity. It is known to be due to an increase in vascular oxidative stress due to a decrease in nitric oxide and an increase in reactive oxygen species (ROS). Nitric oxide, produced by endothelial nitric oxide synthase, is a potent vasorelaxant and inhibits platelet aggregation, vascular muscle cell proliferation, monocyte deposition, and atherosclerosis-related protein expression, thereby regulating the overall cardiovascular homeostasis. Plays an important role (Forstermann et al. , Circulation, 113: 1708-1714, 2006). However, the production of nitric oxide decreases due to increased activity of various enzymes responsible for the generation of free radical species in blood vessels due to various factors [Gryglewski et al. , Nature, 320: 454-456, 1986; Paravicini et al. , Circulation Research, 91: 54-61, 2002; Dusting et al. , Clinical and Experimental Pharmacology and Physiology, 25: S 34-41, 1998], In addition, the produced reactive oxygen species regulate the expression of adhesion molecules [Lo et al. , Am. J. Physiol., 264: L406-412, 1993], stimulation of proliferation and migration of vascular smooth muscle cells [Vriendling and Ushio-Fukai, J. Lab. Clin. Med., 132: 9-15, 1998], causing oxidative lipoprotein regulation, resulting in cardiovascular disease (Lynch and Frei, J. Lipid Res., 34: 1745-1753, 1993). In addition, increased production of reactive oxygen species in blood vessels is associated with clinical risk factors of atherosclerosis and the nitric oxide (NO) function of damaged vascular endothelial cells in patients with coronary artery disease. Causes contraction [Guzik et al. , Cir. Res., 86: E85-90, 2000].

Overall, induction of vascular endothelial cell type nitric oxide synthase and direct reduction of free radical species and inhibition of downstream generation of reactive oxygen species have been recognized as important targets in the prevention and treatment of cardiovascular diseases [Forstermann et al. . , Circulation, 113: 1708-1714, 2006].

To date, nitrorusside and nitroglycerine are present as nitric oxide regulators, but they are used only in emergencies such as heart attack due to resistance and toxicity in clinical use. In addition, many antioxidants such as vitamin C are known and used for various purposes, but the antioxidant effect alone is difficult to improve vascular endothelial dysfunction and related cardiovascular treatments.

Quercus salicina , on the other hand, is an evergreen oak tree that does not fall off during the winter. The leaves are alternate, lanceolate or long oval lanceolate, 10 to 14 cm in length, with sharp tips and sharp teeth on the upper edge. The hairs are on both sides of the leaf but gradually disappear, the back side is white, and the petiole is 1 cm long. In Korea, it grows in the islands and beaches of the south, including Jeju Island, Ulleungdo, Wando, Geoje Island, and warm places in Japan and China, and is common on the Mediterranean coast in Europe. Since thorn trees were rare in Korea, they were rarely used as medicine in traditional Chinese medicine. In the southern islands of Korea, diarrhea was stopped or bleeding blood, and boils and swelling medicines were used in the private sector. It is a tree that has been used as a folk remedy to remove stones in the body in Shikoku region of Japan. In China and Japan, it is a special medicine that stops diarrhea, stops bleeding, removes inflammation, strengthens the kidneys and bladder, and dissolves and removes various stones such as gallbladder stones and kidney stones. I have been writing stems. Particularly, Nippon Shinyaku (Japan) has succeeded in commercializing the participating tree leaf extract as UROCALUN ^® , and is currently in clinical use as a treatment for gallstones and urolithiasis, and its stability has been proven. In Korea, Ilsung New Drug Co., Ltd. has been importing from Japan New Drug since 1974.

Studies on the constituents of the participating tree include mainly tannins, gallic acid, ellagic acid, redroside 6 "-O-gallate, salidroside 3" -O-gallate, salidroside 4 ', 6 "-di-O-gallate, salidroside 4", 6 "-di-O-gallate, salidroside 3", 4 ", 6" -tri-O-gallate) and the like (Nonaka, G) et al .: Chem. Pharm. Bull, 30 (6), 2061; Nishimara, H. er al .: Chem. Pharm. Bull, 32 (5), 1735, 1741, 1750; Nishimara, H. er al. Chem. Pharm. Bull, 34 (8), 3223). The efficacy of each isolated component has been reported to remove gallbladder stones and kidney stones, inhibit hyaluroronidase, anti-allergy, atopic dermatitis, diabetic improvement, and anti-obesity (Japanese Patent Application No. 1970-24109, Japanese Patent Laid-Open No. 06-239757, Japanese Patent Laid-Open No. 2004-000164, Japanese Patent Laid-Open No. 09-227398).

However, none of the above documents discloses or teaches direct vascular endothelial cell type nitric oxide synthase activity enhancement, vascular oxidative stress inhibition, vascular relaxation effect, and blood pressure regulating effect on the bark extract.

<Preceding technical literature>

(Patent Document 1) Japanese Patent Application No. 1970-24109

(Patent Document 2) Japanese Patent Application Laid-Open No. 06-239757

(Patent Document 3) Japanese Patent Application Laid-Open No. 2004-000164

(Patent Document 4) Japanese Patent Application Laid-Open No. 09-227398

(Non-Patent Document 1) Forstermann et al. , Circulation, 113: 1708-1714, 2006

The inventors of the present invention, while searching for antioxidant and vascular relaxation effects on a number of plant extracts, have a strong antioxidant effect, and at the same time, direct vascular endothelial cell type nitric oxide synthase activity enhancement, vascular relaxation and blood pressure control. It confirmed that there was an effect and completed this invention.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for the prevention and treatment of cardiovascular diseases, which is conceived in order to solve the above-mentioned problems, containing the extract of the participating tree as an active ingredient.

It is another object of the present invention to provide a dietary supplement for the prevention of cardiovascular diseases, which contains the extract of Siengsi as an active ingredient.

The pharmaceutical composition for the prevention and treatment of cardiovascular diseases of the present invention is characterized in that it contains the extract of the participating tree as an active ingredient in order to achieve the object as described above.

In addition, the participation tree extract can be extracted from the leaves.

In addition, the participation tree extract can be extracted with an aqueous ethanol solution of 30 to 95% by weight.

In addition, the participating tree extract may have an effect of increasing the activity of vascular endothelial cell type nitric oxide synthase.

In addition, the participating tree extract may have a vasorelaxant effect.

In addition, the participating tree extract may have antioxidant efficacy.

In addition, the cardiovascular disease may be selected from the group consisting of vascular endothelial dysfunction, congestive heart disease, coronary artery disease, hyperlipidemia, hypotension, arrhythmia, heart failure, vascular restenosis, cerebrovascular disease, peripheral vascular disease and metabolic disease have.

On the other hand, the health functional food for the prevention of cardiovascular diseases of the present invention is characterized by containing the tree extract as an active ingredient.

As described above, the extract of the participating tree of the present invention regulates the contraction and relaxation of vascular smooth muscle while activating vascular endothelial cell type nitric oxide synthase, which is a major factor of vascular protection with antioxidant efficacy. It can be used as a pharmaceutical composition or health functional food for the prevention and treatment of vascular endothelial dysfunction and related cardiovascular diseases because it exhibits a strong vascular relaxation and blood pressure control effect.

1 and 2 are diagrams measuring the vasorelaxant activity and contraction inhibitory effect of the bark extract on porcine coronary artery, respectively.

Figure 3 is a measure of the degree of activity of endothelial cell type nitric oxide synthase (eNOS) by the extract from participating trees.

Figure 4 is a measure of the cytotoxicity of the tree extract when participating.

Hereinafter, preferred embodiments of the present invention will be described in detail. In addition, many specific details such as specific components are described in the following description, which is provided to help a more general understanding of the present invention, and the present invention may be practiced without these specific details. It is self-evident to those who have knowledge of the world. In describing the present invention, when it is determined that a detailed description of a related known function or configuration may unnecessarily obscure the subject matter of the present invention, the detailed description thereof will be omitted.

Participating tree extract of the present invention can be obtained as follows.

Above ground part of the participating tree, more specifically, the leaves can be used without limitation, such as harvested, cultured or commercially available, the solvent for extraction is made of water, lower alcohol of C ₁ to C ₅ and mixtures thereof Selected from the group. The present inventors washed the leaves of the tree with water to remove foreign substances and salts and dried, and then dried at about 5 to 50 times the weight of the tree, and 30 to 95% by weight of ethanol aqueous solution at 50 to 95 ℃ for 1 hour to 7 Extraction during the day may be repeated 2 to 5 times, preferably 3 times, and then concentrated under reduced pressure and / or lyophilized to obtain the extract from participating trees (Harborne. JB, Phytochemical medthods: A guide to modern techniques of plant analysis, 3rd Ed., pp. 6-7, 1998).

The present invention provides a pharmaceutical composition for the prevention and treatment of cardiovascular diseases, containing as an active ingredient, the extract of the participating tree obtained by the above method.

The pharmaceutical composition for preventing and treating cardiovascular diseases according to the present invention comprises 0.1 to 99% by weight of the extract based on the total weight of the composition.

The pharmaceutical composition comprising the extract from the participating tree of the present invention may further include appropriate carriers, excipients and diluents commonly used in the preparation of the composition.

Pharmaceutical dosage forms of the extracts of the present invention may be used in the form of their pharmaceutically acceptable salts, or may be used alone or in combination with other pharmaceutically active compounds, as well as in a suitable collection.

Pharmaceutical compositions comprising extracts according to the invention, respectively, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, external preparations, suppositories and sterile injectable solutions according to conventional methods. Can be formulated and used.

Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may comprise at least one excipient in the extract, for example starch, calcium carbonate, sucrose. Or lactose, gelatin, or the like is mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.

Liquid preparations for oral administration include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. have.

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the water-insoluble and suspending agents, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween, cacao butter, laurin butter, glycerogelatin and the like may be used.

Preferred dosages of the extracts of the present invention vary depending 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. However, for the preferred effect, the extract of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.

The present invention provides a health functional food comprising the extract and a food acceptable food supplement additive exhibiting a prophylactic effect of a cardiovascular disease.

Health functional foods to which the tree extract can be added include, for example, various general foods, beverages, gums, teas, vitamin complexes, and the like.

In addition, the participating tree extract may be added to food or beverage for the purpose of preventing cardiovascular diseases. At this time, the amount of the extract in the food or beverage may be added to 0.01 to 15% by weight of the total food weight, the health beverage composition may be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 g. have.

The health functional beverage composition of the present invention is not particularly limited to other ingredients in addition to containing the extract as an essential ingredient in the indicated ratio, and may contain additional ingredients such as various flavoring agents or natural carbohydrates as in general beverages. . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a flavoring agent other than the above-mentioned, a natural flavoring agent, taumartin, a stevia extract, for example, rebaudioside A, glycyrrhizin, etc .; And synthetic flavoring agents such as saccharin, aspartame and the like. The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 g of the composition of the present invention.

In addition to the above, the extract of the present invention has various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, coloring and neutralizing agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective properties Colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the extracts of the present invention may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components can be used independently or in combination. At this time, the ratio of the additive is not very important but is generally selected in the range of 0.01 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

EMBODIMENT OF THE INVENTION Hereinafter, the Example of this invention is described.

Example

Example: Preparation of Participating Tree Extract

After collecting the collected leaves of the tree with water, removing foreign matters and salts, dried and crushed, and adding 25 g of the leaves of the tree and 500 ml of 70% by weight of ethanol aqueous solution to the extracting container, and reflux-cooled for 3 hours at 3 ℃. Repeated heating and extracting several times, and then filtered through a filter paper, the filtrate was concentrated under reduced pressure and lyophilized in a water bath of 40 ℃ 7.0 participating tree leaf extract 7.0 g was obtained.

Test Example 1: Determination of Antioxidant Activity of Participating Tree Extracts

Antioxidant activity was measured by DPPH (1,1-diphenyl-2-pycryl-hydrazyl) method to determine the antioxidant activity (Taco, T. et al., Biosci. Biotech. Biochem., 1994, 58,1780). -1783; Na, MK et al., Nat. Prod. Sci., 2002, 8, 26-29). DPPH is a relatively stable free radical, which exhibits maximum absorbance at 517 nm when it is in radical state, and loses absorbance when it is eliminated. Specifically, take the extract of the leaves of the participating trees, diluted with 3.125, 6.25, 12.25, 25 and 50 ㎍ / ㎖ using DMSO (Sigma, USA), and then put 10 ㎕ each of the solution in a 96 well plate 2 190 μl of a DPPH (Sigma, USA) solution of 10 × ⁴ M / ml ethanol concentration was added thereto, and the mixture was left at room temperature for 30 minutes, and then absorbance was measured at 517 nm. As a control, DMSO was added instead of the sample to investigate the degree of absorbance reduction of the sample. DPPH radical scavenging activity was calculated according to the following equation. As a result, the antioxidant activity increased as the concentration of wood extract increased, and it was confirmed that the substance had a very high antioxidant effect.

Equation 1

A _control : Absorbance of control group without sample

A _sample : Absorbance of reaction group to which sample is added

Table 1

DPPH radical scavenging activity (%)
1 μg / ml	3 μg / ml	10 μg / ml	30 μg / ml	100 μg / ml
9.5	17.2	35.5	78.9	92.3

Test Example 2: Measurement of Vascular Relaxation and Vasoconstriction Inhibitory Effect of Tree Extracts (Cortex Artery)

In order to confirm the vasorelaxant effect of the tree extract prepared by the above example, the relaxation effect of the coronary artery of the pig heart was compared, and the results are shown in FIGS. 1 and 2. Coronary arteries were harvested from the slaughterhouse immediately after the slaughtered pig heart, and then extracted with 18 mM NaCl, 4.7 mM KCl, 1.1 mM MgSO ₄ , 1.2 mM KH ₂ PO ₄ , 1.5 mM CaCl ₂ , 25 mM NaHCO ₃ , and 10 mM glucose. It was placed in the containing Krebs solution (pH 7.4) to remove connective tissue and fat, and made into sections of about 3 mm in length.

After the prepared coronary sections were fixed in a solution of Krebs at 37 ° C. saturated with 95% O ₂ and 5% CO ₂ gas, an isometric tension was applied by a force-displacement transducer (HougSachs, Germany). Measurement was performed using a mounted physiometer (Grass physiograph, HugoSachs, Germany). Coronary artery was first contracted with 80% of vascular maximal contraction with thromboxane derivative U46619 (1-60 nM), and after 10 minutes, it was relaxed with 300 nM Bradykinin to measure the safety of vascular endothelial cells. Next, it was washed three times with Krebs solution and the experiment was performed. Vasorelaxant effect change measurements were first contracted to U46619, followed by a concentration dependent test of the relaxation response by participating tree extract. In addition, U46619 was dose-dependently treated 30 minutes prior to the contraction of the bark extract, and then U46619 was dose-dependently treated to confirm the contraction inhibition effect by the bark extract.

This test was repeated with blood vessels extracted from 4 to 5 different individuals, and the ED 50 value indicates the concentration of the sample (μg / ml) in which the contracted vessel showed 50% vascular relaxation by sample treatment.

TABLE 2 Relaxation Effect of Tree Extracts from Porcine Coronary Artery

	ED50 (μg / ml)
Participating tree extract	23.7

As a result of the test, as shown in FIG. 1, the extract of participating trees of the present invention began to relax significantly in a concentration-dependent manner, and at 102 μg / ml, 102 ± 4% of relaxation was performed. As shown in Table 2, the participating tree extract has a very good degree of relaxation of blood vessels in the coronary artery. In addition, as shown in Figure 2 it was confirmed that having a dual effect of suppressing the contraction of blood vessels by vascular contraction factors such as U46619.

Test Example 3: Endothelial cell type nitric oxide synthase activity test

Effects of vascular endothelial nitric oxide synthase (eNOS) of calf vascular endothelial cells As a serine residue phosphorylation degree 1177 was compared, the results are shown in FIG.

First, vascular endothelial cells were mixed with DMEM (Dubleco's minimum essential medium) and 10% FBS (Fetal bovine serum) solution, followed by incubation for 24 hours in a culture medium without FBS. After the cells stabilized, the samples were treated at each concentration and allowed to react for 30 minutes. The protein was then extracted, centrifuged and the supernatant removed to remove debris from the cells. The extracted protein was electrophoresed on SDS-polyacrylamide gel and blot the protein of the gel with a nitrocellulose membrane. After blocking for 1 hour with 3% BSA, phospho-eNOS and phospho-Akt antibodies (Cell Signaling, USA) were incubated at 4 ° C. overnight at a ratio of 1: 1000. Next, the secondary antibody diluted at a ratio of 1: 2000 was treated, incubated at room temperature for 1 hour, and then developed by chemiluminescence.

As a result, as shown in Figure 3, the participating tree extract can be seen that the increase in the activation of vascular endothelial cell type nitric oxide synthase (phospho-eNOS) that produces nitric oxide is large.

Test Example 4: Cytotoxicity test of participating tree extract

The degree of cytotoxicity of the tree extracts obtained by the examples was compared and the results are shown in FIG. 4.

The arterial blood vessel smooth muscle cells were mixed with MEM (minimum essential medium) and (Fetal bovine serum) solution, 10% FBS and cultured for 24 hours under the conditions of 5% CO _2/37 ℃. After the cells were stabilized, the extracts of the participating trees obtained in the above example were treated and shaken to react for 24 hours. Then, MTS solution (cellTiter 96 Aqueous One Solution, Promega, USA) was added and incubated for 1 hour, and then absorbance was measured at 490 nm.

As shown in FIG. 4, the participating tree extract of the present invention does not have any effect on the survival of cells and can be seen as a very safe drug.

Test Example 5: Statistical Processing

The significance of the test results was determined to be a significant difference when the p was less than 0.05 through the Student's t-test and one-way ANOVA test.

The following describes an example of a pharmaceutical composition comprising the extract of the present invention and a dietary supplement, but this is not intended to limit the present invention only intended to be described in detail.

Formulation Example 1 Preparation of Powder

20 mg of tree extract powder

Lactose 100 mg

Talc 10 mg

The above ingredients were mixed and filled in airtight cloth to prepare a powder.

Formulation Example 2 Preparation of Tablet

10 mg of tree extract powder

100 mg corn starch

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components was prepared by tableting according to the conventional tablet manufacturing method.

Formulation Example 3 Preparation of Capsule

10 mg of tree extract powder

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 2mg

According to a conventional capsule preparation method, the above ingredients were mixed and filled into gelatin capsules to prepare capsules.

Formulation Example 4 Preparation of Injection

10 mg of tree extract powder

Mannitol 180 mg

Sterile distilled water for injection 2794 mg

Na ₂ HPO ₄ 12H ₂ O 26 mg

It was prepared in the above ingredient content per ampoule (2 mL) according to a conventional injection method.

Formulation Example 5 Preparation of Liquid

10 mg of tree extract powder

10 g of isomerized sugar

5 g of mannitol

Purified water

According to the conventional liquid preparation method, each component is added and dissolved in purified water, lemon flavor is added, then the above ingredients are mixed, purified water is added, the whole is adjusted to 100 ml and sterilized by filling in a brown bottle. It was.

Formulation Example 6 Preparation of Healthy Drink

10 mg of tree extract powder

15 g of vitamin C

100 g of vitamin E (powder)

Iron lactate 19.75 g

3.5 g of zinc oxide

Nicotinamide 3.5 g

0.2 g of vitamin A

0.25 g of vitamin B1

0.3 g of vitamin B2

Water

After mixing the above components according to a conventional healthy beverage production method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated and stored in the present invention Used to prepare a healthy beverage composition according to. Although the composition ratio is a composition suitable for a preferred beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

In the above description of the preferred embodiment of the present invention, the present invention is not limited to the specific embodiments described above, those skilled in the art various modifications without departing from the gist of the present invention Of course it is possible. Therefore, the scope of the present invention should not be construed as being limited to the above embodiments, but should be defined by the claims below and equivalents thereof.

The present invention can be used as a pharmaceutical composition for the prevention and treatment of cardiovascular diseases containing the extract of the participating tree as an active ingredient, comprising the extract and a food-acceptable food supplement additive exhibiting a preventive effect of cardiovascular diseases Available as a dietary supplement.

Claims (7)

1. A pharmaceutical composition for the prevention and treatment of cardiovascular diseases, containing the extract of the participating tree as an active ingredient.
2. The method according to claim 1,

   The participation tree extract is a pharmaceutical composition for the prevention and treatment of cardiovascular diseases, characterized in that the extract of participating tree leaves.
3. The method according to claim 1,

   The participating tree extract is a pharmaceutical composition for the prevention and treatment of cardiovascular diseases, characterized in that extracted with 30 to 95% by weight of ethanol aqueous solution.
4. The method according to claim 1,

   The participation tree extract is a pharmaceutical composition for the prevention and treatment of cardiovascular diseases, characterized in that it has an effect of increasing the activity of vascular endothelial cell type nitric oxide synthase.
5. The method according to claim 1,

   The participating tree extract is a pharmaceutical composition for the prevention and treatment of cardiovascular diseases, characterized in that it has a vascular relaxation effect.
6. The method according to any one of claims 1 to 5,

   The cardiovascular disease is selected from the group consisting of vascular endothelial dysfunction, congestive heart disease, coronary artery disease, hyperlipidemia, hypotension, arrhythmia, heart failure, vascular restenosis, cerebrovascular disease, peripheral vascular disease and metabolic disease Pharmaceutical composition for the prevention and treatment of cardiovascular diseases.
7. Health functional food for the prevention of cardiovascular disease, which contains tree extract as an active ingredient.

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