KR101691605B1 - Pharmaceutical composition and fuctional food composition for prevention or treatment of hyperlipidemia comprising the tsaoko fructus extract - Google Patents

Abstract

The present invention relates to a natural extract effective for the prevention or treatment of hyperlipidemia comprising an over-extract as an active ingredient, and is useful as a pharmaceutical composition for preventing or treating hyperlipidemia as well as a health functional food.

Description

TECHNICAL FIELD The present invention relates to a pharmaceutical composition and a functional food composition for prevention or treatment of hyperlipidemia comprising an over-extract as an active ingredient, and a pharmaceutical composition and a functional food composition for treating hyperlipidemia comprising the tsaoko fructus extract,

The present invention relates to a pharmaceutical composition and a health functional food composition for preventing or treating hyperlipidemia comprising an over-extract as an active ingredient.

In modern society, the obesity population is rapidly increasing due to the convenient living environment due to rapid automation, the excessive nutrition consumption due to the increase of processed food and eating out, and the decrease of the physical activity, and accordingly, the insulin resistance, dyslipidemia, hypertension, Metabolic diseases such as arteriosclerosis and hyperlipidemia are increasing.

Hyperlipidemia refers to a state in which abnormal amounts of lipids such as free cholesterol, cholesterol ester, phospholipid, and triglyceride are increased in the blood. Hyperlipidemia is not usually symptomatic in itself, but if there is a lot of fat in the blood, it sticks to the wall of the blood vessel and causes atherosclerosis, which can cause coronary heart disease, cerebrovascular disease, peripheral vascular occlusion (E. Falk et al., Circulation 92, 657-671, 1995). In addition, the excessive fat component as described above accumulates in the liver tissue, which may cause fatty liver. In the above, the proportion of fat in the liver exceeds 5% by weight of the liver, and can be induced not only by excessive fat intake but also by alcohol consumption.

On the other hand, as a method for decreasing the blood lipid concentration, it is recommended that diet, exercise, and medication to suppress the intake of foods containing a lot of cholesterol or saturated fatty acid and to reduce caloric intake. However, diet and exercise therapy are difficult to manage and implement strictly, and there are many limitations in its effectiveness. The lipid concentration reduction agents developed so far include bile acid binding agents, agents that lower cholesterol levels such as HMG-CoA Reductase Inhibitors, Neomycin, and Probucol, and fibrin acid derivatives, Drugs that lower the triglyceride content such as nicotinic acid and fish oil have been developed and used as therapeutic agents. However, these drugs have side effects such as hepatotoxicity, gastrointestinal disorders and carcinogenicity.

Accordingly, studies on natural products that can prevent or treat hyperlipidemia, arteriosclerosis and fatty liver by reducing the excess lipid concentration in the blood even though they are safe to the human body and have no side effects are underway. For example, methanol extracts from cultured wild ginseng have been reported to lower total cholesterol and LDL-cholesterol levels and elevate HDL-cholesterol levels in hyperlipidemic rats induced by high fat diet (EJ Lee et al. , Kor J. Pharmaceon, 34: 179-184, 2003). In addition, it has been reported that the petroleum ether extract of Panax ginseng and the panaxydol contained in the extract have an activity of inhibiting cholesterol absorption (HCHyun et al., J. Ginseng Res., 25, 166, 2001), cholesterol-lowering effects of oyster, manure, and oyster mushroom powder have been reported (BK Kim et al., J. Korean Soc. Food Sci., Nutr., 30, 510-515, 2001).

Under the above circumstances, the inventors of the present invention have been studying natural medicines for preventing or treating diseases caused by hyperlipidemia such as hypertriglyceridemia, hypercholesterolemia or arteriosclerosis, and found that excess extract regulates blood cholesterol Thereby effectively lowering the cardiovascular risk index and arteriosclerosis index, thereby completing the present invention.

It is an object of the present invention to provide a pharmaceutical composition or a health functional food composition comprising, as an active ingredient, an over-extract capable of preventing or treating hyperlipemia.

In order to solve the above problems, the present invention provides a pharmaceutical composition for preventing or treating hyperlipidemia comprising an over-extract as an active ingredient.

As used herein, the term " overgrown "refers to dried excess fruit belonging to the ginger family, and is referred to as excess, nose or excess phosphorus, , Nausea, vomiting and diarrhea.

The term "extract" as used in the present invention means a specific component extracted from a liquid solvent in excess. As the solvent, water, methanol, ethanol, or a mixture thereof may be used. It is preferable to extract with ethanol to efficiently extract the active ingredient. The concentration of ethanol is preferably 10% to 90%, but is not limited thereto.

The over-extract of the present invention may be any one selected from the group consisting of cold extraction, ultrasonic extraction, room temperature extraction, hot water extraction, reflux cooling extraction, and steam extraction.

The term "hyperlipidemia" as used herein means hypertriglyceridemia or hypercholesterolemia.

As used herein, the term "prevention" refers to any act that inhibits or delays disease by administration of a composition comprising the over-extract. The term "treatment ", as used herein, refers to any action that improves or alleviates symptoms of hyperlipemia upon administration of a composition comprising the over-extract.

The composition of the present invention may contain, for administration, a pharmaceutically acceptable carrier, excipient or diluent in addition to the above-described effective ingredients. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The composition of the present invention may be formulated in the form of oral, granule, tablet, capsule, suspension, emulsion, syrup, aerosol or the like oral preparation, external preparation, suppository or sterilized injection solution according to a conventional method. In detail, when formulating, it can be prepared by using diluents or excipients such as fillers, weighing agents, wetting agents, disintegrating agents, surfactants and the like which are usually used. Solid formulations for oral administration include, but are not limited to, tablets, pills, powders, granules, capsules, and the like. Such solid preparations can be prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc., in the over-extract. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration, liquid paraffin, and various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and tasks. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. As a base for suppositories, it is possible to use witepsol, macrosole, tween 61, cacao paper, laurin, glycerogelatin and the like.

The composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the desired method, and the dose may be determined depending on the condition and weight of the patient, The mode of administration, the route of administration, and the time, but may be suitably selected by those skilled in the art. The daily dose of the over-extract is preferably 1 mg / kg to 500 mg / kg, and may be administered once to several times per day, if necessary.

The present invention also provides a health functional food composition for preventing or ameliorating hyperlipidemia comprising an over-extract as an active ingredient.

The health functional food may contain flavoring agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and thickening agents (cheese, chocolate etc.), pectic acid and its salts, alginic acid and its salts, Organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. It can also contain natural fruit juices and pulp for the production of fruit juices and vegetable drinks. These components may be used independently or in combination. The health functional food may be in the form of any one of meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, .

In addition, the health functional food may further include food additives, and the suitability of the food functional food as a "food additive" is not limited to the corresponding items in general rules and general test methods approved by the Food and Drug Administration It is judged according to the standards and standards.

Examples of the products that have been used in the above-mentioned "food additives" include natural products such as ketones, chemical products such as glycine, potassium citrate, nicotinic acid and cinnamic acid, sensory coloring matter, licorice extract, crystalline cellulose, high- - Mixed preparations such as a sodium glutamate preparation, a noodle-added alkaline agent, a preservative preparation, a tar coloring agent and the like.

The excess extract according to the present invention, which is added to a food containing beverages in the process of manufacturing a health functional food, can suitably increase or decrease its content, if necessary, and is preferably 1 to 15% by weight %. ≪ / RTI >

The present invention is a natural extract effective for the prevention or treatment of hyperlipidemia, and can be used not only as a pharmaceutical composition for preventing or treating hyperlipidemia but also as a health functional food.

Figure 1 is a graph showing the relationship between serum total cholesterol (T.CHO, mg / dL), triglyceride (TG, mg / dL), HDL (mg / dL) And (D) LDL (mg / dL) analysis results.
FIG. 2 is a graph showing the (a) cardiovascular risk index (AI) and (a) arteriosclerosis index (CRF) calculated through blood analysis results (Table 1) according to an embodiment of the present invention.
FIG. 3 shows the result of glucose tolerance test of an experimental animal having a high carbohydrate diet according to an embodiment of the present invention.
FIG. 4 is a graph showing the results of measurement of blood insulin levels in experimental animals in which a high carbohydrate diet is controlled according to an embodiment of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples. However, the following examples and experimental examples are provided for illustrating the present invention, and the scope of the present invention is not limited thereto.

Example : Manufacture of excess extract

To 5 kg of excess dryness, 25 L of 80% fermentation ethanol was added and the mixture was extracted by cold extraction twice for 24 hours, and then concentrated under reduced pressure to obtain an ethanol extract (G47).

Experimental Example : In - vivo  analysis

1) Experimental animal and sample administration

Six-week-old C57BL / 6 mice were arranged in descending order of weight, and 10 mice were separated per group so that the mean and standard deviation between the groups were uniform. A sample (the excess extract prepared in the Example) was administered once a day together with a high carbohydrate diet for 8 weeks. Samples were orally administered at a dose of 100 mg / kg to 400 mg / kg per day and doses of 10 mg / ml to 40 mg / ml were administered daily at 3:00 pm in consideration of physiological conditions and dietary habits of the experimental animals . The vehicle was administered PBS, vehicle was administered in the normal group, and omega - 3 was administered in the positive control group. Each group is shown in Table 1 below.

division sample Dose Normal group PBS 200 μl to 300 μl Negative control group PBS 200 μl to 300 μl Positive control group Omega-3 660 mg / kg G47 100 Excess extract 100 mg / kg G47 200 Excess extract 200 mg / kg G47 400 Excess extract 400 mg / kg

2) Analysis of weight change

The body weight was measured twice a week by administering the sample for 8 weeks according to the method of Experimental Example 1 above. The measurement results are shown in Table 2 below.

division Day 1 Weight (g) Day 8 Weight (g) Weight change on the last day of experiment (g) Normal group 21.43 + - 0.4 32.45 ± 1.3 11.41 Negative control group 22.14 ± 0.5 34.32 ± 3.1 12.18 Positive control group 21.45 ± 0.2 32.32 ± 2.1 10.87 G47 100 21.63 ± 0.3 33.47 ± 2.1 11.84 G47 200 21.73 ± 0.3 34.22 ± 2.2 12.49 G47 400 21.34 ± 0.3 33.76 ± 1.9 12.42

3) Blood biochemical analysis

After the 8-week sample administration period of Experimental Example 1), the animals were anesthetized with isoflurane / oxygen to collect blood from the abdominal cavity and analyzed for blood. GOT, GPT, CREA (Creatinine), BUN, γ-GT, and ALP were used as an automatic analyzer (7020, HITACHI, Japan) after centrifugation at 3,000 rpm using a centrifuge (Centrifuge 5415R, eppendorf) LDL, HDL, TG (Triglyceride), T. CHO (total cholesterol) and TP (total ptotein) analysis were performed. The atherogenic indices (AI) and the cardiac risk factor (CRF) used to determine the risk of cardiovascular disease were calculated by the following equation. The results are shown in Table 3, Fig. 1 and Fig.

division TP (g / dL) ALB (g / dL) GOT (U / L) GTP (U / L) BUN (mg / dL) LDH (U / L) Normal group 4.91 ± 0.32 1.45 ± 0.11 131.0 + - 26.2 95.5 ± 22.4 24.6 ± 2.6 167.0 + - 66.8 Negative control group 5.05 + - 0.38 1.54 + 0.13 137.6 ± 31.4 97.4 ± 23.7 25.3 ± 3.6 182.7 ± 57.4 Positive control group 5.03 + - 0.41 1.50 + - 0.10 125.0 + - 22.5 90.5 ± 22.4 24.3 ± 2.9 161.3 ± 47.0 G47 100 5.10 + - 0.47 1.60 + 0.09 129.3 ± 21.6 94.3 ± 31.6 24.4 ± 4.5 167.5 ± 63.1 G47 200 5.29 ± 0.51 1.56 + 0.11 134.1 ± 19.5 95.7 ± 52.4 26.2 ± 1.6 172.5 ± 19.5 G47 400 4.88 ± 0.43 1.51 + 0.06 128.7 ± 13.5 95.8 ± 35.8 24.8 ± 1.8 165.7 ± 39.6 division T.CHO (mg / dL) GLU (mg / dL) TG (mg / dL) T-BIL (mg / dL) HDL (mg / dL) LDL (mg / dL) Normal group 52.3 ± 11.9 148.1 ± 27.3 53.5 ± 10.4 0.00 ± 0.01 37.9 ± 8.0 6.54 + - 0.74 Negative control group 173.7 ± 46.3 142.9 ± 19.4 131.9 ± 25.3 0.01 ± 0.01 69.0 ± 13.5 9.65 ± 0.79 Positive control group 89.8 ± 22.1 136.0 + - 23.5 87.0 + - 11.3 0.01 ± 0.00 44.5 ± 12.8 6.76 + - 0.72 G47 100 168.0 + - 39.3 144.2 + - 22.3 110.4 ± 16.4 0.02 ± 0.01 69.9 ± 10.9 8.65 ± 0.81 G47 200 176.1 ± 30.5 145.2 ± 19.3 109.9 ± 14.4 0.02 ± 0.01 67.0 + - 10.4 7.56 ± 1.09 G47 400 143.1 ± 37.2 132.7 ± 19.5 100.0 13.8 0.01 ± 0.00 69.4 ± 12.3 7.01 + - 0.67 division IP (mg / dL) CREA (mg / dL) γ-GT (U / L) AI CRF Normal group 5.07 ± 0.11 0.32 ± 0.01 0.34 ± 0.05 0.38 + 0.43 1.38 + - 0.43 Negative control group 5.37 + 0.18 0.34 + 0.03 0.38 ± 0.01 1.52 + - 0.51 2.52 + - 0.51 Positive control group 5.11 ± 0.96 0.31 + 0.03 0.39 + - 0.05 1.02 + - 0.48 2.02 ± 0.48 G47 100 5.03 + - 0.36 0.32 ± 0.01 0.38 + 0.04 1.40 0.51 2.40 ± 0.51 G47 200 5.20 ± 1.03 0.34 + 0.02 0.42 + 0.07 1.63 + - 0.50 2.63 ± 0.50 G47 400 5.25 ± 0.91 0.33 ± 0.01 0.37 + 0.08 1.06 + - 0.37 2.06 ± 0.37

4) glucose tolerance test and blood insulin concentration measurement

To investigate the occurrence of diabetes mellitus, which is a common complication of persistent high - carbohydrate diets, glucose intakes and blood insulin levels were analyzed.

First, glucose tolerance test was performed for the insulin function test in laboratory animals whose blood lipid and glucose levels were elevated by high carbohydrate diet. 2 g / kg of glucose was injected into the abdominal cavity of the experimental animals which were fasted for 12 hours after the end of the 8-week sample administration period of Experimental Example 1) at 0, 30, 60, 120 and 240 minutes The glucose level was measured by glucose oxidase method. The results are shown in Fig.

Next, biotin-conjugated anti-insulin (primary antibody) and plasma samples were reacted for 2 hours on an anti-insulin coated plate using a mouse insulin ELISA kit (SHIBAYAGI, Japan) After washing, HRP-conjugated streptavidin (second antibody) was added and reacted for 30 minutes. After stopping the reaction, the reaction was stopped by adding stop buffer to the chromoqenic substrate for 4 times. After the absorbance was measured at 450 nm using an ELISA reader (Molecular Devices, USA), the insulin standard curve (0, 0.156, 0.313, 0.625, 1.25, 2.5, 5, 10 ng / ml). The results are shown in Fig.

As shown in FIG. 3 and FIG. 4, it was confirmed that the over-extract of the above example did not affect blood glucose level and insulin concentration, but exerted selective action on only hyperlipemia.

Claims (8)

A pharmaceutical composition for the prevention or treatment of hyperlipidemia comprising an excess extract as an active ingredient.
The pharmaceutical composition according to claim 1, wherein the excess extract is prepared by extracting an excess thereof with water, ethanol or a mixed solvent thereof.
The pharmaceutical composition according to claim 2, wherein the extraction is an ultrasonic extraction, a room temperature extraction, a hot water extraction, a cold extraction, a reflux cooling extraction, or a steam extraction.
delete The present invention relates to a health functional food composition for preventing or ameliorating hyperlipidemia, which comprises an excessive extract as an active ingredient.
[Claim 6] The health functional food composition of claim 5, wherein the excess extract is prepared by extracting the excess extract with water, ethanol or a mixed solvent thereof.
The health functional food composition according to claim 6, wherein the extraction is ultrasonic extraction, room temperature extraction, hot water extraction, cold extraction, reflux cooling extraction, or steam extraction.
delete

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