KR20040059173A - Composition for preventing cardiovascular diseases - Google Patents

Abstract

PURPOSE: Provided is a composition for prevention of cardiovascular diseases, which composition characteristically contains extracts of Curcuma Longa L., green tea, black tea, ginkgo leaf and grape seed. It has anti-thrombosis and anti-hyperlipemia activities. CONSTITUTION: A composition for prevention of cardiovascular diseases characteristically contains 5-40 wt.% of Curcuma Longa L. extract, 1-10 wt.% of green tea extract, 1-10 wt.% of black tea extract, 0.1-1 wt.% of ginkgo leaf extract and 0.5-5 wt.% of grape seed extract. It further contains fish oil, preferably DHA or EPA.

Description

Composition for preventing cardiovascular diseases

The present invention is an invention for a cardiovascular disease prevention composition comprising turmeric extract, green tea extract, black tea extract, ginkgo biloba extract and grape seed extract.

Recently, cardiovascular disease, which is represented by myocardial infarction or stroke, has the highest mortality rate than malignant tumors. It is widely reported that the causes of diet include westernization of diet, genetic factors, smoking, drinking, high blood pressure, diabetes, obesity, lack of exercise, and excessive stress.

In vivo, blood is always balanced by a complex and sophisticated control system so that flow is not interrupted by bleeding or blood clots under normal conditions. However, if this equilibrium is broken due to various factors, blood vessel flow is not smooth and cardiovascular disease occurs. Atherosclerosis is the most representative of cardiovascular diseases, and is a very dangerous disease causing myocardial infarction or cerebral infarction by causing ischemic conditions in important organs such as the heart and brain.

When atherosclerosis occurs, vascular endothelial damage and dysfunction occur. When vascular endothelial cells are degraded or damaged, high cell adhesion molecules are expressed, resulting in adhesion of monocytes, T-lymphocytes, and platelets. Invading into the vascular wall between the endovascular cells. Monocytes that enter the walls of the blood vessels are transformed into macrophages by phagocytosis of lipoproteins, proliferation and activation of smooth muscle cells in the walls of the blood vessels to produce an extra celluar matrix, which further accumulates fat and causes atherosclerosis. When arteriosclerosis occurs, blood vessels are weakened and their flexibility decreases, and they can easily be ruptured by weak stimuli.In this case, when extracellular matrix such as collagen in the inner wall of blood vessels is exposed, platelets in the blood adhere, activate, aggregate, and The clotting system is activated to form a rapid blood clot. This phenomenon is often observed in case of sudden death due to myocardial infarction. If the coronary artery of the deceased patient is examined under a microscope, the narrowing of blood vessels due to atherosclerosis and the clot of blood vessels can be seen. As a result, the blood supply to the heart is momentarily blocked, causing tissue necrosis through the ischemic state. Therefore, in order to effectively prevent cardiovascular diseases, it is required to lower blood cholesterol, inhibit platelet activity and coagulation activity, inhibit the proliferation of vascular smooth muscle cells causing vascular restenosis.

Due to the high incidence and mortality of vascular diseases, research is being actively conducted with much medical attention. For the prevention and treatment of thrombotic diseases, thrombolytics, antiplatelets, and anticoagulants are commonly used (Jung Kwang Hoe. Research and development of new antithrombotic agents. Korean Hemostatic Society 1996; 3: 1-12. ). Thrombolytic agents such as urokinase and t-PA are used as effective treatments to help the blood flow by dissolving the formed clots. Aspirin, an antiplatelet agent, has excellent effects, but side effects such as gastrointestinal disorders have been reported (Miwa K, Kambara). H, Kawai C. Effect of aspirin in large doses on attacks of variant angina.Am Heart J. 1983; 105: 262-273. ), The anticoagulant coumadine is a long-term primary, with side effects of bleeding due to too strong activity. There is a limit to use as a prophylactic agent. The administration of such effective drugs is a prescription for secondary prevention for patients who have already developed cardiovascular disease to the last, and the primary preventive drug for the prevention has not been developed in the world. In this study, we attempted to develop materials from natural products with the aim of developing an effective primary preventive agent that can reduce the incidence rate before cardiovascular disease.

Recently, many studies have been conducted to clarify the antithrombotic and anti-arteriosclerosis activity of foods ingested on a daily basis, based on the high correlation between the incidence of cardiovascular disease and diet. This effort aims to anticipate the primary preventive and therapeutic effects on these diseases by identifying and ingesting effective components related to the cardiovascular system from food materials that are safe for humans.

The present invention has been made by the necessity as described above, an object of the present invention to provide a composition for preventing cardiovascular disease mainly made of natural materials.

1 is a diagram showing the effect of a composition of the present invention on total cholesterol and cholesterol ester amounts.

Figure 2 shows the effect of the composition of the present invention on HDL-cholesterol (a) and LDL-cholesterol (b) concentrations .

Figure 3 shows the HDL / LDL-cholesterol ratio (a) and arteriosclerosis index (b) after administration of the composition of the present invention.

4 shows the effect of the composition of the present invention on platelet aggregation activity.

In order to achieve the above object, the present invention provides a composition for preventing cardiovascular diseases, including turmeric extract, green tea extract, black tea extract, ginkgo biloba extract, grape seed extract.

When the composition of the present invention is less than the effective amount of each component, the present invention does not exhibit the effect intended, and when the effective amount is exceeded, there is a fear of side effects and rather a tendency to decrease the effect, as shown in Table 1 below. It is desirable to have an effective amount of each component.

In addition, the composition of the present invention most preferably has the optimum composition of Table 1 below.

TABLE 1 Optimum composition, effective amount and range of each component of the composition of the present invention

Ingredient Name Optimum composition (% by weight) Effective use (% by weight) shape Curcuma longa 18 5-40 powder Black Tea (Theae sinensis) 6.5 1-10 powder Green tea (Camelliae sinensis) 5.0 1-10 powder Grape seed (Vitis vinifera) 1.5 0.5-5 powder Gingko folium 0.5 0.1-1 powder Fish oil (DHA / EPA) 60 30-80 oil Remainder 8.5 2-20 powder all 100 100

Hereinafter, the present invention will be described in more detail with reference to non-limiting examples and experimental examples.

Example: Preparation of Composition

The machinery used for manufacturing was sterilized, disinfected or washed to prevent foreign substances from being mixed or contaminated with heterologous microorganisms, and the raw materials processed by appropriate methods were supplied from Byoverd Co., Ltd. to ensure good quality and freshness. Refined fish oil (600g), turmeric extract powder (180g), grape seed extract (150g), green tea extract (50g), ginkgo leaf extract (5g), and other vitamins (85g) are accurately weighed and put into a mixer at 80 degrees for 3 hours. While homogeneously blended to produce a composition of the present invention.

Experimental Example

The turmeric extract, green tea extract, black tea extract, ginkgo biloba extract, grape seed extract and DHA (docasahexaenoic acid), EPA (eicosapentaenoic acid) used as a natural plant material used in the present invention were supplied and used by Bioverd.

Collagen used for the measurement of platelet aggregation activity was Chrono-Log Co. The anticoagulant activity was measured by BioMerieux (France), and the human fibrinogen and thrombin, which were used for thrombolytic activity, by Green Cross (Korea). Meanwhile, curcumin, the main experimental material, and aspirin used as a positive control drug were Sigma Co. It was purchased from (USA), and the kit used for measuring lipid profile related items such as cholesterol and triglyceride was used as Asan Pharmaceutical Co., Ltd. (Korea). Other necessary reagents used express reagents as much as possible.

The hypercholesterol model experimental animals were 3 weeks old Sprague Dawley male rats (about 70g, Daehan Biolink Co., Ltd.). Each experimental animal was divided into 8 normal groups and 24 hyperlipidemic groups (hyperlipidemic induction and administration) after being fed to rats for 5 days. Normal rats were fed powdered rat chow, and hyperlipidemic groups were fed high fat and high cholesterol diets and their respective administrations for 7 weeks.

As a breeding environment, the temperature was maintained at 22 ± 2.0C˚ humidity 55 ± 5.0% and the lighting cycle was adjusted to 12 hours. The diet was fed with water between 10 am and 11 am daily, and the amount of diet was measured every time the diet was fed.

The animals were fasted 12 hours before sacrifice, anesthetized with diethyl ether, and fresh blood was collected from the abdominal aorta and used for the analysis of platelet aggregation ability. The anticoagulant used was sodium citrate. Whole blood was collected and the remaining blood was centrifuged at 4,500 rpm for 10 minutes to obtain plasma and used as a sample for the rest of the experiment.

Investigation of Changes in Risk Factors for Hyperlipidemia in Laboratory Animals

Body weight change and feed efficiency were measured by fasting 12 hours every week for the first day of the experiment and measuring the weight change of the animals until the end of the experiment. The feed efficiency ratio (weight gain g / feed intake g) was calculated from the feed intake and body weight gain during the entire experiment.

Total triglycerides in serum obtained by centrifugation were measured by the change of absorbance at 550 nm using enzyme kit (Asan Pharmaceuticals) according to Bucolo method, and total cholesterol in blood was measured by 500 nm using kit (Asan Pharmaceuticals) by enzyme method. Absorbance was measured at and colorimetric determination. HDL-cholesterol was measured by precipitating and removing cholesterol except for HDL-cholesterol in serum, and measuring the supernatant in the same manner as the total cholesterol in blood. LDL-cholesterol was measured in the same manner as total cholesterol by precipitating only LDL-cholesterol in serum as a separate solution. Blood free cholesterol, cholesterol esters and blood phospholipids were measured by colorimetric measurement using an enzyme kit (Asan Pharmaceuticals).

The experimental results were as follows.

Hyperlipidemia experiments were performed to determine the changes in total cholesterol and Cholesterol ester concentrations in normal, control, turmeric and composition groups. In the case of total cholesterol concentration, the cholesterol level of the control group was 212 mg / dl, which was 2.9 times higher than that of the normal group after 6 weeks of hyperlipidemia. In comparison, the total group of cholesterol was decreased in the administration group of each group, and the composition group was reduced by about 29% compared to the control group. The turmeric group showed about 24% lower level than the control group (see FIG. 1).

In the case of cholesterol ester and free cholesterol concentrations, it was observed that their concentration was significantly increased in the control group. In detail, the amount of cholesterol ester was 29% less in the composition group and 14.6% less in the turmeric group.

Changes in LDL-cholesterol concentration associated with atherosclerosis were measured and compared with changes in HDL-cholesterol concentration. In the case of plasma HDL-cholesterol concentration, each group was administered with a hyperlipidemic diet for 6 weeks, and the control group showed a significant decrease in HDL-cholesterol content compared to the normal group. The amount of HDL-cholesterol was small in the decrease with respect to the normal group concentration. The HDL-cholesterol concentrations in the turmeric extract group and the mixture group were decreased by 43.8% and 41.9%, respectively, compared to the control group, which showed 46.6% and 51.5% of HDL-cholesterol levels, respectively, compared to the control group. It can be seen that there is a synergistic effect (see FIG. 2A). In the case of LDL-cholesterol, the amount of the control group was increased by about 5.59 times compared to the normal group, showing the characteristics of hyperlipidemic animals, and the administration group of each group showed a change in the suppression of hyperlipidemia with a lower concentration than the control group. In general, hyperlipidemic animals are characterized by significantly higher total cholesterol levels than normal, and when viewed in detail, higher cholesterol LDL-cholesterol is observed than good cholesterol HDL-cholesterol. This not only interferes with the smooth flow of blood, but also increases the frequency of arteriosclerosis, which causes various cardiovascular diseases. On the other hand, the composition group was found to reduce the amount of LDL-cholesterol by about 32% compared to the control group, and the turmeric group also showed a reduction effect of about 27% (see Fig. 2b).

In the change of triglyceride concentration, the control group increased 1.8 times compared to the normal group, and the triglyceride concentrations in the turmeric extract and mixture treatment groups decreased by 15% and 31%, respectively. Seemed.

After 6 weeks of hyperlipidemia, the ratio of HDL / LDL-cholesterol in the control group showed a change of about 10-fold, resulting in a significant decrease in the amount of good cholesterol HDL-cholesterol compared to the normal group. Comparing the administration of each group, the HDL / LDL-cholesterol ratio of the composition group was about 1.7 times higher than the control group (see Fig. 3a).

After 6 weeks of hyperlipidemia, the atherosclerosis index, which was calculated based on the amount of total cholesterol and HDL-cholesterol, a good cholesterol, was found to be significantly increased in the control group compared to the normal group. When the administration of each group was examined, the composition group was about 56% lower than the control group, and the turmeric group was observed to be reduced by about 48% (see FIG. 3B).

Platelet aggregation inhibitory activity (Ex vivo test)

Platelet aggregation activity was measured using a platelet aggegometer (Chrono-log Co., USA), using the electrical conductivity measurement method (impedance method) using whole blood. Fresh blood was carefully collected from the abdominal aorta of a total of 40 experimental animals, and collagen-induced platelet aggregation activity was performed. Platelet aggregation activity was warmed at 37 to 3 minutes after the preheated silicon-coated coagulated cuvette was mixed well with 0.45ml physiological saline with the stirrer bar. After addition of collagen (1mg / ml), platelet aggregation inhibition was measured by impedance method using platelet aggregometer.

The results were as follows.

The change of platelet aggregation ability in normal and hyperlipidemic animals was investigated by measuring the electrical conductivity using whole blood. For changes in platelet aggregation capacity in high cholesterol models. The control group, which is a high cholesterol group compared to the normal group, increased by 1.75 times in platelet aggregation, which showed a sensitive change in platelet aggregation. This is a result showing that high cholesterol concentration in the blood is likely to form a blood clot, and when turmeric and the composition group were administered, platelet aggregation was reduced by 21.1% and 29.1%, respectively, to observe the inhibitory effect of platelet aggregation. (See Figure 4)

As a result of examining platelet aggregation after two weeks of administration in normal animals rather than platelet aggregation in hyperlipidemic animals, the administration groups of each group showed improved changes in platelet aggregation compared to the normal group that consumed only normal diet. In the case of turmeric and composition group, aspirin, a typical drug commonly used as an antiplatelet agent, was improved by 26% compared to the normal group.

In the animal experiments of orally administering the composition of the present invention (100 mg / day) for one week, the platelet aggregation rate was suppressed by about 29% compared to the normal group to which nothing was administered. This corresponds to almost the same inhibition pattern as the control group administered aspirin (100 mg / kg). In addition, in the animal experiments in which hyperlipidemic diets were administered for 6 weeks, the composition of the present invention was combined with the total cholesterol of about 29%, cholesterol ester of about 29%, and LDL-cholesterol of about 10.0% compared to the control group that ingested only of hyperlipidemia. It was found to reduce 32%. In particular, it was observed that the arteriosclerosis index of the composition-administered group of the present invention was significantly reduced by at least 56% compared to the control group.

These results can be used as a preventive agent of cardiovascular diseases having the effective antithrombotic and antihyperlipidemic activity of the composition of the present invention, and because it is a food material can greatly reduce the side effects of existing drugs.

Claims (4)

A composition for preventing cardiovascular diseases, including turmeric extract, green tea extract, black tea extract, ginkgo biloba extract, and grape seed extract. The method of claim 1, The composition is characterized by comprising 5-40% by weight turmeric extract, 1-10% by weight green tea extract, 1-10% by weight black tea extract, 0.1-1% by weight ginkgo leaf extract and 0.5-5% by weight grape seed extract. To prevent cardiovascular disease composition. The method of claim 1, The composition of the cardiovascular disease prevention composition, characterized in that it further comprises fish oil. The method of claim 3, wherein The fish oil is a composition for preventing cardiovascular disease, characterized in that DHA or EPA.