KR101461588B1 - Pharmaceutical composition for preventing or treating arteriosclerosis - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for the prevention or treatment of arteriosclerosis including cinnamon, pine needle, corn and licorice, a composition for suppressing obesity, a functional food for preventing or improving arteriosclerosis comprising the above components, Prevention or amelioration. The composition of the present invention exhibits a weight loss, a decrease in fat tissue weight, a decrease in blood glucose level, a decrease in blood triglyceride level, a decrease in blood cholesterol level, an increase in blood insulin level, an anti-arteriosclerosis and an anti-platelet aggregation effect, The present invention can be widely applied to the development of a pharmaceutical composition or health functional food for prevention and treatment.

Description

[0001] The present invention relates to a pharmaceutical composition for preventing or treating arteriosclerosis,

The present invention relates to a pharmaceutical composition for the prevention or treatment of arteriosclerosis, and more particularly to a pharmaceutical composition for preventing or treating arteriosclerosis including cinnamon, pine needle, And a functional food for preventing or ameliorating obesity including the above-mentioned components.

Due to the recent abundance and diverse changes in diet and lifestyle, nutritional intake is likely to be in an unbalanced state, and mechanized modern life has resulted in lack of exercise. As a result, the morbidity of chronic diseases such as hypertension is increasing, and the form of disease is changing to advanced countries. There are various factors such as age, sex, smoking, obesity, lack of exercise, stress, dietary and related diseases besides genetic predisposition as a risk factor and inducer of arteriosclerosis which is a main cause of ischemic heart disease. Changes in lipid composition are the most important causes.

In particular, elevated serum total cholesterol and low-density lipoprotein (LDL) cholesterol and decreased HDL cholesterol are known to be the major causes, and oxidized LDL (oxidized LDL) is known to be an important cause of coronary artery disease. It has been studied so far that oxidized LDL penetrates rapidly through the scavenger receptors and binds to the phagocytic cells, and this process is not regulated by existing blood lipid levels and is not able to migrate back into the blood The concentration of oxidized LDL in the inner membrane rapidly increases. The foam cells formed during this process produce atherosclerotic lesions through stages of fatty streaks, fibrous plaques, and complicated lesions leading to macrovascular complications, , Diabetes mellitus patients, and high mortality rates.

High-density lipoprotein (HDL) plays a role in transferring and storing cholesterol in the liver to the liver. HDL concentration in the blood is closely related to heart disease, atherosclerosis, and coronary artery disease. Low-density lipoprotein (LDL) plays a role in supplying liver stored cholesterol to blood vessels and tissues and interacting with HDL. Low HDL and high LDL levels in the blood increase the risk of heart disease, atherosclerosis, coronary artery disease, and the like. Therefore, these two levels of blood concentration can be an important strategy for prevention or treatment of the various diseases mentioned above.

These blood cholesterol concentrations are controlled by the amount of cholesterol that is controlled by biosynthesis, but excessive amounts of it may lead to various metabolic diseases. Excessive intake of high fat leads to hyperlipemia, leading to various cardiovascular diseases such as atherosclerosis. The hyperlipidemia is an abnormally increased concentration of cholesterol, triglyceride, phospholipid and free fatty acid in the blood. The most directly influencing factors are blood cholesterol and low density lipoprotein (LDL) -cholesterol, and various Among cardiovascular diseases, it is known to cause atherosclerosis and other atherosclerosis.

The above-mentioned atherosclerosis is a clinically important problem because it accumulates thick lipid along the blood vessel wall to reduce blood flow and cause ischemic heart disease, angina pectoris and myocardial infarction. Hypertension, hyperlipidemia, and smoking are the three major risk factors that promote the development of atherosclerosis. In addition, the incidence of hypertension, diabetes, obesity, stress, and so on . Atherosclerosis does not interfere with activity, but arteriosclerosis causes coronary artery disease to become atherosclerotic if it is narrowed or clogged by more than 50 to 70% of coronary tissue. Arterial sclerosis is a major cause of arterial rupture, which is a major cause of various circulatory diseases such as hypertension, angina pectoris, cerebrovascular disease (stroke).

To overcome these cardiovascular diseases, various therapeutic agents have been developed and some have been commercialized. However, since the various therapeutic agents developed so far have been reported to have side effects, although there are differences in the degree of the research, researches are being continued to develop therapeutic agents derived from natural products without side effects.

For example, Japanese Patent Laid-Open Publication No. 1995-53393 discloses an arteriosclerosis inhibitor comprising extract of licorice root. Japanese Patent Application Laid-Open No. 2004-60098 discloses a method of treating arthritis, which comprises extracting garlic, pine needle, Discloses a composition for preventing or treating obesity and atherosclerosis contained as a component, and Japanese Patent No. 294091 discloses a composition for preventing and treating arteriosclerosis, Discloses a pharmaceutical composition for the treatment and prevention of arteriosclerosis and hypertension containing Curcuma aromatica Salisb. Extract. However, there is a disadvantage that a composition showing the effects of prevention, improvement and alleviation of arteriosclerosis arising from these natural substances is not excellent in the therapeutic effect instead of securing safety, and studies for overcoming such disadvantages are continuing have.

Under these circumstances, the present inventors have intensively studied to develop a therapeutic agent derived from a natural product, which exhibits safety but has a therapeutic effect on atherosclerosis. As a result, it has been found that a composition containing an extract of cinnamon, pine needle, It was confirmed that not only the therapeutic effect of arteriosclerosis but also the effect of suppressing obesity are exhibited, and the present invention has been completed.

One object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of arteriosclerosis, which comprises cinnamon, pine needle, corn, licorice.

It is another object of the present invention to provide a composition for suppressing obesity, which comprises cinnamon, pine needle, gilt, and licorice.

Another object of the present invention is to provide a functional food for preventing or improving arteriosclerosis, which comprises cinnamon, pine needles, lupine and licorice.

It is still another object of the present invention to provide a functional food for preventing or improving obesity, which comprises cinnamon, pine needle,

As one embodiment for achieving the above object, the present invention provides a pharmaceutical composition for preventing or treating arteriosclerosis including cinnamon, pine needles, lupine and licorice.

The term "arteriosclerosis" of the present invention refers to a disease that causes decrease of elasticity of blood vessel wall, increase of resistance to blood flow, increase of blood pressure and hypertrophy of left ventricle due to thickening of inner wall of artery , Stroke, myocardial infarction, angina pectoris, coronary atherosclerosis, and atherosclerosis. For the purpose of the present invention, the arteriosclerosis is used as an objective disease that can be prevented, alleviated, ameliorated or treated by administration of the composition of the present invention, but is not particularly limited thereto.

The term "prevention" of the present invention means any action that inhibits or slows the onset of arteriosclerosis by administration of the composition. For the purpose of the present invention, the prevention can be understood as an action to inhibit or delay the onset of arteriosclerosis using the composition of the present invention, but is not particularly limited thereto.

The term "treatment" of the present invention means any action that improves or alleviates symptoms due to arteriosclerosis by administration of the composition. For the purpose of the present invention, the treatment may be understood to mean an action of improving symptoms of arteriosclerosis or alleviating pathological symptoms using the composition of the present invention, but the present invention is not limited thereto.

The composition of the present invention includes cinnamon, pine needles, lupine and licorice, preferably cinnamon, pine needles, lupine, licorice or their extracts, more preferably solvent extracts of cinnamon, pine needles, do. The content of cinnamon, pine needles, licorice and licorice contained in the composition is not particularly limited but may be 1 to 20 parts by weight, respectively. The solvent is not particularly limited, but water, a lower alcohol having 1 to 4 carbon atoms , Acetone, hexane, chloroform, ethyl acetate, butylene glycol and the like can be used.

In addition, the extraction method for obtaining the above extract is not limited. However, the method of extracting the above-mentioned cinnamon, pine needles, wool, licorice, etc. separately or by adding them to the solvent may be used. In order to remove solid particles after extraction, Or a filtration method using a freezing filtration method may be further used. Further, a conventional purification process may be further used. The conventional purification process is not particularly limited, but a constant molecular weight cut-off value may be used Separation using an ultrafiltration membrane having a specific surface area, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), vacuum distillation, freeze drying, spray drying and the like.

According to one embodiment of the present invention, the composition of the present invention (KIOM-18) was prepared by immersing a mixture of cinnamon, pine needle, ganoderma lucidum and licorice in distilled water and then extracting it by filtration and freeze-drying. As a result of analyzing the components contained in the above-mentioned composition, it was found that Liquiritin exhibiting anti-inflammatory effect, ferulic acid exhibiting antioxidative effect, hypoglycemic effect and cholesterol-lowering effect, Liquiritigenin, Cinnamic acid, UV inhibitory effect, Glycyrrhizin, which shows tumor suppression effect, cholesterol reduction effect and liver protective effect, antitumor effect, antioxidative effect, anti-inflammatory effect etc. (Curcumin), etc., which are shown in Fig. 1 (Fig. 1).

The composition of the present invention can be used to prevent or treat atherosclerosis by administering to a subject who is or may be at risk of arteriosclerosis.

The term "individual" of the present invention means all animals, including humans, who have developed or are capable of developing arteriosclerosis.

At this time, the administration route of the composition can be administered through any ordinary route as long as it can reach the target tissue. The composition of the present invention may be administered intraperitoneally, intravenously, intramuscularly, subcutaneously, intradermally, orally, intranasally, intrapulmonarily, or rectally, though it is not intended to be limited thereto. In addition, the composition may be administered by any device capable of transferring the active agent to the target cell.

The inventors of the present invention have found that, in order to develop a therapeutic agent having a therapeutic effect on arteriosclerosis, which is derived from a natural product and exhibits safety, it can be used as a medicament for the treatment of atherosclerosis, A variety of traditional medicinal herbs such as Suseoboyuan, Bonchogujin, Jinmokokgangsan, Sunoltongsan, and others. , It was expected that cinnamon, pine needle, ugum and licorice could be safely used as a constituent component of a composition having a therapeutic effect for arteriosclerosis.

First, in the case of cinnamon, it is stated that it comes from the characteristic aspect of the spirits, the sweet, the large heat, the spleen, the heart and the liver. , There is the effect of the effect in terms of the Bo Yuan (补 元 阳), 비 胃 (胃 胃), 積 積 cold, It has the effect of accelerating blood circulation, and it healing warms the inside of the body, makes the blood circulation well, smoothes the liver and lungs, and rats and the blood coagulate ≪ / RTI >

Next, it is described that in the case of the pine needle, it returns to the pine, warm, nontoxic, heart, and plexus in terms of characteristics, (祛风濕 药), which has the efficacy belonging to the 风风濕 药 (祛风濕 药), which treats the sickness which is caused by the deceit of the custom by removing the customs of the 絡 絡 絡, The enemy is to heal the boils of the customs, to heal the hair, to make the five oars, to not hunger, to live long, to treat hypertension, limb disturbance due to peripheral blood circulation disorder, insomnia, paralysis and nervous breakdown .

Secondly, it is described that in the case of Ulgum, it is called "Shin", "Suffer", "Cold", "Liver", "Suffer" and "Heart" , There is a pharmacological effect that lowers the blood lipid (blood lipid), and the blood circulation in the effect side. It is said to cure the blood (blood product), to lower the flounder, to heal the hemorrhoids and the pus, to get injured in the metal, and to treat the heartache (heartache).

Finally, in the case of licorice, in terms of characteristics, sex is flat, beauty is sweet, and heart, lung, spleen, stomach (stomach) It is said that it is effective in terms of effect in terms of the effect of the pharmacokinetics, the warming, the detoxification, the harmonious pharmacology, and the therapeutic effect. It is said that there is a scent of 热 热 (寒热 邪气) in the five-pitched meat, and it is said that it passes through the 9 九 하고 (九 竅) and makes all blood circulation well.

According to one embodiment of the present invention, extracts were obtained from the four selected natural products, and the effect of the composition containing these extracts was evaluated. Specifically, when the composition (KIOM-18) was administered to a model of Ldlr - / - arteriosclerosis disease, the body weight of the control was significantly reduced (FIG. 2) (Table 1), the weight of adipose tissue was significantly decreased (FIG. 3), and the blood glucose level was significantly decreased (FIG. 4) compared to the control group, and the blood triglyceride level was significantly lower than that of the control group (FIG. 5), the level of LDL-cholesterol in the blood was slightly reduced (FIG. 6), the blood insulin level was significantly decreased (FIG. 7), and the intimal thickness was remarkably thinner than that of the control (Fig. 8).

In order to confirm the effect of KIOM-18 on platelet aggregation, the effect of each component constituting KIOM-18 and KIOM-18 in platelet aggregation induced samples by collagen treatment was examined. As a result, KIOM-18 Showed the most excellent platelet aggregation inhibitory effect and cinnamon showed excellent platelet aggregation inhibitory effect among the above components (Fig. 9). On the other hand, as a result of confirming whether each component constituting KIOM-18 and KIOM-18 induces platelet aggregation by itself, it was confirmed that cinnamon itself can induce platelet aggregation, but the KIOM- 18 did not exhibit any effect of effective platelet aggregation (Fig. 10).

The composition of the present invention may further comprise a pharmaceutically acceptable diluent, excipient or carrier. The composition comprising a pharmaceutically acceptable carrier can be of various oral or parenteral formulations. 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 tablet pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose ), Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are also 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 may be any one selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, nonaqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories It can have a formulation.

The term "pharmaceutically effective amount" of the present invention means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, meaning that the composition of the present invention can be administered in a pharmaceutically effective amount. The effective dose level is determined by the type and severity of the subject, the age, sex, activity of the drug, sensitivity to the drug, time of administration, route and rate of excretion, duration of treatment, Can be determined according to the element. 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 administer an amount that will achieve the maximum effect in the least amount without side effects.

In addition, the composition of the present invention can be used alone or in combination with methods using surgery, hormone therapy, drug therapy and biological response modifiers for the prevention or treatment of cardiovascular diseases.

As another embodiment for achieving the above object, the present invention provides a composition for suppressing obesity, which comprises cinnamon, pine needle, corn and licorice.

The term "obesity" of the present invention is generally referred to as " obesity " when an excess amount of adipose tissue is present in the body or when the body mass index (body mass index, body weight index divided by the square of height . In individuals with obesity symptoms, the fatty acids and glucose that enter the adipocytes from plasma are usually esterified and accumulate in the form of triglycerides. For the purpose of the present invention, the obesity symptom is used as a target disease which can be prevented, alleviated, ameliorated or treated by administration of the composition of the present invention, but is not particularly limited thereto.

In addition, the definition, manufacturing method, content, etc. of each component constituting the composition are the same as those of the pharmaceutical composition for preventing or treating arteriosclerosis.

The composition of the present invention may be used for the prevention of obesity by the possibility that obesity symptoms are likely to occur or by administration to an individual who has developed it.

The term "individual" of the present invention means all animals, including humans, who have developed or are capable of developing obesity symptoms.

At this time, the administration route of the composition can be administered through any ordinary route as long as it can reach the target tissue. The composition of the present invention may be administered intraperitoneally, intravenously, intramuscularly, subcutaneously, intradermally, orally, intranasally, intrapulmonarily, or rectally, though it is not intended to be limited thereto. In addition, the composition may be administered by any device capable of transferring the active agent to the target cell.

According to one embodiment of the present invention, extracts were obtained from the four selected natural products, and the effect of the composition containing these extracts was evaluated. Specifically, when the composition (KIOM-18) was administered to a model of Ldlr - / - arteriosclerosis disease, the body weight of the control was significantly reduced (FIG. 2) (Table 1), the weight of adipose tissue was significantly decreased (FIG. 3), and the blood glucose level was significantly decreased (FIG. 4) compared to the control group, and the blood triglyceride level was significantly lower than that of the control group (FIG. 5), and the blood LDL-cholesterol level was slightly lower than that of the control group (FIG. 6), and the blood insulin level was significantly decreased as compared with the control group (FIG. 7).

The composition of the present invention may further comprise a pharmaceutically acceptable diluent, excipient or carrier, and the formulations, formulation methods, and additional ingredients used herein may be used in combination with the pharmaceutical compositions for the prevention or treatment of arteriosclerosis described above, It is the same without.

As another embodiment for achieving the above object, the present invention provides a health functional food for preventing or ameliorating arteriosclerosis comprising the composition or a health functional food for preventing or improving obesity.

According to one embodiment of the present invention, the effect of the composition of the present invention is analyzed using an atherosclerotic model mouse, and as a result, the composition exhibits an anti-arteriosclerotic effect (FIG. 8) The health functional food may be added to the food for the purpose of preventing or improving the health functional food. The health functional food is not particularly limited, but may be a health functional food, a nutritional supplement, a nutritional agent, a pharmafood, It can be any type of food such as nutraceutical, designer food, food additive and the like, preferably meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gum, , Various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes. At this time, the method of adding is appropriately used according to a conventional method, and the amount to be added can be suitably determined according to the intended use (prevention, health or therapeutic treatment).

The health functional food of the present invention may further include various components other than the above-mentioned composition. These various components are not particularly limited, but preferably include various nutrients, vitamins, electrolytes, flavors, colorants, Alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, they may contain flesh for the production of natural fruit juice, fruit juice beverage and vegetable beverages to add palatability and / or functionality, and these ingredients may be used independently or in combination.

The composition of the present invention exhibits a weight loss, a decrease in fat tissue weight, a decrease in blood glucose level, a decrease in blood triglyceride level, a decrease in blood cholesterol level, an increase in blood insulin level, an anti-arteriosclerosis and an anti-platelet aggregation effect, The present invention can be widely applied to the development of a pharmaceutical composition or health functional food for prevention and treatment.

BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a diagram showing the result of analysis of herbal medicine extract KIOM-18 of the present invention by HPLC. FIG.
FIG. 2 is a graph showing changes in body weight over time while administering western type diets and KIOM-18 to LDLr k / o mice for 20 weeks.
FIG. 3 is a graph showing changes in weight of adipose tissue following administration of KIOM-18 after administration of Western diet to LDLr k / o mice for 14 weeks.
Figure 4 is a graph showing the effect of KIOM-18 on blood glucose levels.
Figure 5 is a graph showing the effect of KIOM-18 on serum triglyceride levels.
Figure 6 is a graph showing the effect of KIOM-18 on blood LDL-cholesterol levels.
Figure 7 is a graph showing the effect of KIOM-18 on blood insulin levels.
Figure 8 is a micrograph showing whether KIOM-18 causes histopathological changes.
FIG. 9 is a graph showing the effect of KIOM-18 or various starches on collagen-induced platelet aggregation.
FIG. 10 is a graph showing the platelet aggregation ability of KIOM-18 or various endosymbionts.

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example  1: Preparation of KIOM-18 candidate for blood circulation improvement

The blood circulation improving candidate substance was prepared by extracting cinnamon, pine needles, licorice and licorice, and the mixture was mixed with 260 g of cinnamon, 260 g of pine needles, 280 g of curd and 200 g of licorice, and the mixture was immersed in 20 L of distilled water for 1 hour. (500 ml) and 150 ㎛ (standard testing sieve, Aperture 500 ㎛ and 150 ㎛), and the filtrate was lyophilized to obtain a blood circulation improving candidate substance KIOM-18 was prepared.

Example  2: Component analysis of KIOM-18

The HPLC system was composed of L-2130 pump, L-2200 auto-sampler, L-2350 column oven and L-2455 diode array UV / VIS detector using an Elite Lachrom HPLC system (Hitachi Co., OptimaPak C18 (5 m, 100 A, 4.6 mm x 250 mm, RStech Co., Korea) was used, and the column oven was maintained at 30 ° C. The mobile phase was a gradient solvent system (5 to 100% acetonitrile mixed solvent, time: 60 min, flow rate: 1 ml / min) in which the ratio of the mixed solvent of water for HPLC and acetonitrile was changed. KIOM-18 and standard products Dissolved in methanol and adjusted to a concentration of 100 mg / mL, filtered through a 0.45 μm filter, and injected with 10 μl (FIG. 1). At this time, the UV wavelength of the DAD detector was selected to be 237 nm in which all the peaks of the KIOM-18 were evenly distributed. 1 is a graph showing the results of analysis of the blood circulation improving candidate substance KIOM-18 by HPLC. As shown in FIG. 1, the blood circulation improving candidate substance KIOM-18 is a combination of Liquiritin which exhibits an anti-inflammatory effect, ferulic acid which exhibits antioxidative, hypoglycemic and cholesterol-lowering effects, (Liquiritigenin), Cinnamic acid which shows ultraviolet blocking effect, Glycyrrhizin which shows tumor suppression effect, cholesterol reduction effect and liver protective effect, antitumor effect, antioxidative effect, anti-inflammatory effect (Curcumin).

Example  3: LDL  Receptor deficiency Ldlr - / -) Evaluation of Efficacy of KIOM-18 as a candidate for blood circulation improvement in atherosclerotic mouse model

Example  3-1: Ldlr - / - Preparation of atherosclerotic mice

Experimental animals were obtained from male Jackson LDLr k / o mouse, an animal model of arteriosclerosis. The experimental animals were housed in a 10-week-old mouse with good health (25 ± 2 ° C), humidity (50 ± 5%), ) And 12 hour light period (light on 07: 00 ~ 19: 00). Animals were divided into four groups and fed diets and drinking water freely.

Example  3-2: Ldlr - / - weight and weight of atherosclerotic mice Dietary efficiency  Measure

LDLr k / o mice were adapted with a basic diet (AIN-76A diet) for 2 weeks and then fed a Western diet containing 0.15% cholesterol and 21% neutral fat and no cholate at 10 weeks of age Together, KIOM-18 was administered for 20 weeks in parallel. The LDLr k / o mouse is a mouse (Ldlr - / -) deficient in LDL receptor derived from C57BL / 6 mouse, and has an LDL + VLDL cholesterol increase without changing the HDL cholesterol level and a total cholesterol level more than twice . However, when the Western diet is administered for 3 months, the lesion does not occur in the C57BL / 6 mouse, and the atherosclerosis can be induced in the LDLr k / o mouse. Therefore, .

The food efficiency ratio (FER), which is the amount of food intake and weight gain, was calculated as the ratio of the total weight gain to the total food intake (FIG. 2 and Table 1). At this time, LDLr k / o mice in which only Western type feed was administered for 20 weeks as a control group were used, and the LDL r k / o mice were administered with a normal diet as a reference value and measured in an animal model (WT) (Li sun, Cardiovascular Research, 82: 371-381, 2009).

FIG. 2 is a graph showing changes in body weight over time while administering western type diets and KIOM-18 to LDLr k / o mice for 20 weeks. As shown in FIG. 2, the body weight of the control (Negative Control) was increased by 98.3% (18.2 g) compared to the initial body weight, and the body weight of KIOM-18 (1.0 g / kg) And the body weight of the KIOM-18 treated group was significantly decreased at the end of the experiment as compared with that of the control group.

Experimental group Dietary intake (g / day) Weight gain (g / day) FER (%) Control group 2.38 0.202 + - 0.01 8.47 ± 0.53 KIOM-18 1.0 g / kg 2.05 0.061 ± 0.00 2.98 ± 0.12

Table 1 shows the measured dietary intake, body weight gain and FER (%) after administration of western diet to LDL rk / o mice for 14 weeks. The FER of the control group was increased by 70.1% (FER, 8.47 ± 0.53%) more than the WT without FER (2.53 ± 0.24%) and the FER of the KIOM-18 ,%) Were significantly decreased compared to the control group.

From the above results, it was found that the dietary intake of KIOM-18 was 2.05 g / day, which was slightly lower than that of the control group (2.38 g / day), but the amount of body weight gain relative to the dietary intake was remarkably decreased.

Example  3-3: Ldlr - / - Measurement of fat tissue in atherosclerotic mice

LDLr k / o mice were adapted to the basic diet (AIN-76A diet) for 2 weeks, followed by 14 weeks of Western diet and KIOM-18 administration at 10 weeks of age. Then, each experimental animal was divided into abdominal, epididymal, and inguinal adipose tissues to measure the total weight of adipose tissues, and the adipose tissues per unit weight (kg) (Fig. 3). At this time, as a control group, LDLr k / o mice in which Western type feed was administered for 20 weeks were used.

FIG. 3 is a graph showing changes in weight of adipose tissue following administration of KIOM-18 after administration of Western diet to LDLr k / o mice for 14 weeks. As shown in FIG. 3, the weight (g) of the adipose tissue of the control (Negative Control) was 6.45 ± 0.43 (g), and the weight of the adipose tissue of the KIOM-18 administration group was significantly decreased as compared with the control.

Example  3-4: Ldlr - / - atherosclerotic mice In plasma  Glucose, insulin and biochemical analysis

LDLr k / o mice were adapted to the basic diet (AIN-76A diet) for 2 weeks, and KIOM-18 was administered in parallel for 12 weeks with western diet from 10 weeks of age. Blood was collected every 30 days from the oropharyngeal vein using a capillary tube and then EDTA was used to prevent coagulation. In order to perform a blood biochemical test, centrifugation was carried out for 30 minutes at 3,000 rpm and 4 ° C for 15 minutes And separated to obtain plasma. The content of blood glucose, triglyceride, low-density lipoprotein (LDL) cholesterol and insulin in the obtained plasma was measured using a biochemical automatic analyzer (Hitachi-720, Hitachi Medical, Japan) 6 and 7). At this time, LDLr k / o mice in which only Western type feed was administered for 20 weeks as a control group were used, and the LDL r k / o mice were administered with a normal diet as a reference value and measured in an animal model (WT) Known blood glucose, triglyceride, LDL cholesterol and insulin levels were used (Li sun, Cardiovascular Research, 82: 371-381, 2009).

Figure 4 is a graph showing the effect of KIOM-18 on blood glucose levels. As shown in FIG. 4, the blood glucose level was increased in the control group (Negative Control) and increased by 98.9% (275.0 ± 20.1 mg / dL) or more compared to the reference value WT (138.2 ± 63.1 mg / dL) When administered, the blood glucose level was significantly reduced as compared with the control group.

Figure 5 is a graph showing the effect of KIOM-18 on serum triglyceride levels. As shown in FIG. 5, in the control group, the blood triglyceride level was increased by 6.6 times (1062.7 ± 95.5 mg / dL) compared with the reference value of WT (139.0 ± 49.0 mg / dL) , The blood triglyceride level was significantly decreased as compared with the control group.

Figure 6 is a graph showing the effect of KIOM-18 on blood LDL-cholesterol levels. As shown in FIG. 6, the blood LDL-cholesterol level was increased in the control group by 9.2 times (412.7 ± 13.2 mg / dL) compared to the reference value of WT (40.2 ± 5.2 mg / dL) The level of LDL-cholesterol in the blood was somewhat lower than that of the control group, but it was not decreased to a significant level.

Figure 7 is a graph showing the effect of KIOM-18 on blood insulin levels. As shown in FIG. 7, the insulin resistance of the control group increased by 8.4 times (6.62 ± 1.68 ng / ml) compared with the reference value of WT (0.7 ± 0.14 ng / ml) . The above IR occurs due to insulin function which lowers blood glucose and prevents cells from burning glucose efficiently. When the IR is high, excessive insulin production leads to an increase in blood insulin level, and an increase in blood insulin level leads to hypertension, Hyperlipemia, type 2 diabetes, and the like. However, when KIOM-18 was administered in combination, blood insulin levels were significantly reduced as compared with the control group.

Example  3-5: lesion size histopathology analysis of aortic arch caused by anti-arteriosclerotic effect

In order to perform histopathological observation on major aortic arch organs, adipose tissue, liver, heart, and aorta were cut and fixed with 10% neutral buffered formalin for 24 hours, (H & E) and oil-red O staining were performed on a 4 μm-thick tissue slice using a microtome, and the tissue or organ was stained with an optical microscope The presence or absence of a specific lesion was observed (Fig. 8).

Figure 8 is a micrograph showing whether KIOM-18 causes histopathological changes. Generally, LDLr k / o mice were treated with Western diet for 14 weeks in a control group (LDLr KO-CT), in which a fatty streak was formed at the onset of atherosclerosis and a necrotic core, cholesterol clefts, and calcification, and progress to lesions that progress to the intermediate stage of fibroproliferative lesions with thick fibrous cap, . As shown in FIG. 8, it was confirmed that intimal thickening (intima thickness, arrow portion) was thickened by inducing fibrotic lesion of the aortic arch wall in the control group (LDLr KO-CT), and KIOM-18 administration group (LDLr KO- 18), it was confirmed that the thickness of the endothelium was significantly thinner than that of the control group.

Example  3-6: KIOM-18's Anti-platelet  Coagulation effect

(Born, GVR and Cross, et al., Nature 194, 927-7), which is a conventional platelet aggregation detection method for measuring the difference in permeability due to platelet aggregation using an aggregometer, 929, 1962), the anti-platelet aggregation effect of KIOM-18 was evaluated.

First, blood was collected in a tube containing 3.8% sodium citrate as an anticoagulant so that the ratio of blood to sodium citrate was 9: 1 from rabbits with normal platelet function. To obtain platelet rich plasma (PRP), the cells were centrifuged at 160 × g (1,000 rpm) for 10 minutes and the platelet count was adjusted to 4 × 10 8 cells / ml using a Hepes buffer (HEPES buffer).

Next, the coagulation measuring instrument (AGGREGOMETER, Chrono-Log Co.) was fixed at 37 ° C and the number of revolutions of 1,000 rpm and corrected to platelet-poor plasma. A sample was added to the platelet-rich plasma, transferred to a measuring instrument, left for 3 to 5 minutes in advance, and collagen was added as a platelet aggregation promoting substance, followed by measurement of agglutination for 10 minutes. Various platelet aggregation agents (licorice, lupine, pine needle, cinnamon) and KIOM-18 were treated at a concentration of 1,000 μg / ml according to the above platelet aggregation test method and their effect on platelet aggregation ability was measured (FIG. At this time, aspirin was used as a positive control group.

FIG. 9 is a graph showing the effect of KIOM-18 or various starches on collagen-induced platelet aggregation. As shown in FIG. 9, in addition to the known aspirin, cinnamon and KIOM-18 effectively inhibited collagen-induced platelet aggregation, and KIOM-18 exhibited remarkably superior effects than cinnamon.

To determine whether the results were due to the lower treatment concentrations of each cinnamon and KIOM-18, various starches (licorice, lupine, pine leaf and cinnamon) and KIOM-18 were mixed at different concentrations (100, 500, 1,000, Ml), and collagen, which is an aggregation promoting substance, was not treated (Fig. 10). FIG. 10 is a graph showing the platelet aggregation ability of KIOM-18 or various endosymbionts. As shown in FIG. 10, it was confirmed that the cinnamon having a concentration of 500 μg / ml or more exhibited platelet aggregation ability as such.

Therefore, the inhibition of the platelet aggregation ability of the cinnamon shown in the results of Fig. 9 is a result of not reacting with the normal platelet aggregation ability but inducing the platelet activity before the collagen promoting substance collagen treatment, .

The results of Examples 3-1 to 3-6 described above show that the composition KIOM-18 of the present invention exhibits excellent blood circulation improving effect.

Claims (9)

A solvent extract of cinnamon, pine needle, lupine, and licorice, and exhibits a platelet aggregation inhibitory action.
The method according to claim 1,
Wherein said arteriosclerosis is a disease selected from the group consisting of stroke, myocardial infarction, angina, coronary atherosclerosis and atherosclerosis.
delete delete The method according to claim 1,
Wherein the solvent extract is an extract extracted with a solvent selected from the group consisting of water, lower alcohols having 1 to 4 carbon atoms, acetone, hexane, chloroform, ethyl acetate and butylene glycol.
delete The method according to claim 1,
Wherein the composition further comprises a pharmaceutically acceptable diluent, excipient or carrier.
A health-functional food for prevention or improvement of atherosclerosis, which comprises a solvent extract of cinnamon, pine needle, lupine and licorice and exhibits a platelet aggregation inhibitory action. delete

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