KR20100031848A - Composition comprising the dried powder of polymnia sonchifolia or the extract therefrom for preventing and treating hyperlipidemia and atherosclerotic-vascular diseases - Google Patents

Abstract

PURPOSE: A composition for preventing and treating hyperlipidemia and atherosclerotic vascular diseases is provided to reduce lipid content in blood and suppress the formation of atheroma. CONSTITUTION: A pharmaceutical composition for preventing and treating hyperlipidemia and atherosclerotic vascular diseases contains dried powder and extract of Polymnia sonchifoia. The dried powder and extract of Polymnia sonchifoia is obtained from leaves, stems, and tuber of the Polymnia sonchifoia. The dried powder of Polymnia sonchifoia is produced through natural dry, freeze dry, and hot air dry. The extract of Polymnia sonchifoia is crude extract, soluble extract of polar solvent or soluble extract of non-polar solvent.

Description

Composition comprising the dried powder of Polymnia sonchifolia or the extract therefrom for preventing and treating hyperlipidemia and atherosclerotic-vascular diseases}

The present invention relates to a composition for the prevention and treatment of hyperlipidemia and atherosclerotic vascular disease, containing yacon dry powder or its extract as an active ingredient.

[Document 1] Statistics of probability of death by cause of death in 2006, Statistics Korea

2 Nature , 362 , p. 801, 1993

[Reference 3] Circulation Res ., 67 , p. 651, 1990

Document 4 Am . Heart J. , 117 , p. 777, 1989

N. Engl ., J. Med ., 318 , p. 1714, 1988

Document 6 Biomed . Environ Sci ., 21 , pp. 91-97, 2008

[Document 7] Asia Pac . J. Clin . Nutr . , 17 , pp.284-287, 2008

8 J. Cell . Biochem . , 104 , pp.1-14, 2008

Document 9 Planta Med . , 73 , pp.1163-1168, 2007

Document 10 Br . J. Nutr . , 97 , pp.776-785, 2007

11 J. Agric . Food Chem . , 54 , pp.1347-1352, 2006

Document 12 Anal . Biochem . , 142 , pp.347-350, 1984

13 Clin . Chem . , 21 , pp.437-441, 1975

Clin . Chem . , 18 , pp.499-502, 1972

15. J. Pharmacol . Exp . Ther . , 317 , pp.627-634, 2006

In general, diseases are expressed in various forms as social, economic, cultural and environmental factors change. Recently, the rapid economic development and the improvement of living standards have led to the diversification of lifestyles, including the diet, which has led to the reduction of past infection-oriented diseases and the increase of chronic degenerative diseases of advanced countries. According to the 2006 mortality statistics by the cause of death in Korea, for men and women over 40 years old, cerebrovascular disease (13.44%), hypertensive disease (2.53%), heart disease (8.97%) and circulatory disease (25.54%) The mortality rate is 50.48%, and the mortality rate from cerebral cardiovascular diseases such as hypertension, arteriosclerosis, ischemic heart disease, cerebral infarction, cerebral hemorrhage and stroke is increasing rapidly. Probability Statistics, Statistics Office].

The cerebral cardiovascular diseases are closely related to blood as the main cause of the increase of blood cholesterol, the change of blood components according to the change of lipid composition and excessive mental tension. Under normal conditions, blood does not aggregate in blood vessels, but when bleeding occurs, one of the body's defenses is blood clotting. However, thrombosis, which is created when blood vessels are damaged due to changes in blood components or when the internal diameter of blood vessels is narrowed due to arteriosclerosis, causes blood flow to the heart through coronary arteries or fine cerebral blood vessels. When blocked, cerebral cardiovascular disease develops. Also, due to the progress of the disease, the risk of recurrence is high, so most cases require lifelong treatment.

Vascular smooth muscle cells, a major cause of atherosclerotic vascular disease, are present in the aorta, alimentary canal, and lung of the aorta in vivo. Excessive proliferation of vascular smooth muscle cells leads to several diseases, such as atherosclerosis, restenosis after angioplasty and lumenal stenosis after vascular transplantation.

Atherosclerosis is a generic term for localized arterial lesions that indicate thickening, remodeling, stiffness, and deterioration of the arterial wall. Are classified. Among these, atherosclerosis is the most important clinical problem for ischemic heart disease, stroke and cerebral infarction.

According to Russelroth's "Injury to Response" [ Nature , 362 , p.801, 1993], a well-known mechanism for the development of atherosclerosis, endothelial cells of blood vessels are injured or stimulate stimulation such as hyperlipidemia, viral infection, and high blood pressure. Upon receipt, various growth factors that promote the proliferation of vascular smooth muscle cells are generated. As a result, vascular smooth muscle cells excessively proliferate to cause thickening of the lining.

As a medical treatment for such cerebral cardiovascular diseases, hyperlipidemia, blood pressure, administration of antioxidants, antiplatelets, vasodilators, anticoagulants, and the like have been administered, but have not been clinically sufficient.

On the other hand, for angina and myocardial infarction caused by atherosclerosis, surgical methods such as percuaneous transluminal coronary angioplast (PTCA), atherosclerosis, laser resection, stent implantation, etc. It has been tried and has had some success.

However, these surgical treatments have a problem in which restenosis occurs in 25 to 49% of patients 3 to 5 months after the surgery. When restenosis occurs as described above, reoperation is required, and thus, the burden on the patient's life and the pressure of insurance finance are very serious problems. Therefore, although various drug administrations are performed for the purpose of suppressing restenosis, these do not show sufficient effect.

Review for the onset, where (機序) of such restenosis step albeit, the proliferation of the intima of the vascular smooth muscle cells has been suggested to be a cause of the recent research in [Circulation Res ., 67 , p. 651, 1990]. In short, restenosis is presumed to have been caused by a balloon catheter or the like, which is caused by excessive progression of the proliferative response of vascular smooth muscle cells started to repair the physically destroyed vascular wall structure. Accordingly, attempts have been made to treat restenosis by inhibiting proliferation of vascular smooth muscle cells in the stenosis. As a specific example, clinical trials with heparin [ Am . Heart J. , 117 , p. 777, 1989; Clinical trials using aspirin and Zipyridamole in combination [ N. Engl ., J. Med ., 318 , p. 1714, 1988], etc., but none effectively suppress the restenosis.

In addition, in the coronary artery that causes excessive stenosis or occlusion that is a cause of ischemic heart disease, in addition to coronary angioplasty, surgery to implant blood vessels (internal thoracic artery, gastric retinal artery, large saphenous vein, etc.) other than one's own coronary artery bypass Reconstruction of blood circulation by (by-pass) surgery is also used clinically.

In such coronary artery bypass surgery, the endothelial thickening of the transplanted blood vessel often occurs, and the blood circulation is hindered by the narrowing of the lumen of the transplanted blood vessel. In the formation of the double membrane thickening, it is known that the proliferation of smooth muscle cells and the generation of extracellular matrix due to it play a central role [ Nippon]. Rinsho , 52 , p 1010, 1994].

Therefore, it is important to treat cerebral cardiovascular disease, which is the leading cause of death worldwide, through various treatment methods as described above, but it is difficult to treat once it occurs and the risk of recurrence is high. It is more important.

Recently, studies on natural products having excellent blood lipid lowering and vascular smooth muscle cell proliferation inhibitory activity have been actively conducted for the prevention and treatment of hyperlipidemia and atherosclerotic vascular disease. In particular, bioactive functions such as maintaining biological defense and homeostasis by food ingredients, preventing disease and fast healing are recognized as a good coping method for diseases related to diet, and are being actively researched and developed.

For example, it has been reported that ingesting kale juice may improve the onset of coronary artery disease in patients with hyperlipidemia [ Biomed . Environ Sci ., 21 , pp.91-97, 2008], The flavonoids of cocoa are known to reduce the incidence of cardiovascular disease [ Asia Pac . J. Clin . Nutr . , 17 , pp. 284-287, 2008]. In addition, hesperetin, a type of flavonoid contained in citrus peel, regulates DNA synthesis and cell cycle at 100 μΜ or less in vascular smooth muscle cell proliferation, an important factor in the development of atherosclerosis. It is known to inhibit effectively by inhibiting protein expression [ J. Cell . Biochem . , 104 , pp.1-14, 2008], cudraflavanone, a flavonoid component of Cudrania tricuspidata, inhibits vascular smooth muscle cell proliferation by inhibiting the Akt pathway, a cell proliferation regulating protein. It is known to suppress strongly [ Planta Med . , 73 , pp. 1163-1168, 2007].

Yacon (Polymnia sonchifolia) is a dicotyledonous perennial tuberous plant belonging to the Asteraceae family, native to Bolivia and Peru, the Andean region of South America, and about 20 species in the tropical climate of South America. Call. The shape of the tuber is similar to dahlia or sweet potato, and the ground part is similar to the pig potato, and the height is about 1.5 ~ 3m. Stems green-purple, hairy, cylindrical or somewhat angled, hollow at maturity. Words are numbered from 15 to 20 branches from the main stem and caused a lot of adventitious roots arise from the rhizome of the eye surface [Br. J. Nutr . , 97 , pp. 776-785, 2007]. The tuber contains several types of carbohydrates, including glucose, monosaccharides such as fructose, disaccharides such as sugar, and oligosaccharides of 3-10 sugars, and contains some starch and inulin. The sweetener is fructo -oligosaccharides) are the main constituent [ Br . J. Nutr . , 97 , pp. 776-785, 2007; J. Agric . Food Chem. , 54 , pp. 1347-1352, 2006]. Yacon is known to have excellent antidiabetic activity and is used to improve diabetic disease. However, studies on physiological activities other than antidiabetic or antioxidant effects on yacon are very poor. As a result, only a small amount of primary products and simple processed products are consumed. Yacon is an unlimited crop resource with new bioactive activity and high-value-added products.

Therefore, the present inventors have continuously studied the effect of yacon dry powder or its extract to improve hyperlipidemia, inhibit vascular smooth muscle cell proliferation, prevent and treat atherosclerotic cardiovascular disease, and then, the blood lipid concentration of hyperlipidemic rabbits ingested with yacon dry powder And experiments in which the formation of intraarterial wall atherosclerosis, that is, in vivo, confirmed the hyperlipidemia improvement and atherosclerosis inhibiting activity of yacon dry powder, and vascular smooth muscle cells isolated from rat arterial vessels. Inhibition of cell proliferation activity using a), ie, in vitro experiment (in vitro) confirmed the arterial smooth muscle cell proliferation inhibitory activity of yacon extract to complete the present invention.

In order to carry out the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of hyperlipidemia and atherosclerotic vascular disease containing yacon dry powder or its extract as an active ingredient.

In addition, the present invention provides a health functional food for the prevention and improvement of hyperlipidemia and atherosclerotic vascular disease containing yacon dry powder or its extract as an active ingredient.

Yacon dry powder or extracts thereof as defined herein are characterized in that they are obtained from leaves, stems or tubers of yacon, preferably tubers.

The dry powder as defined herein is characterized in that yacon is naturally dried, lyophilized or hot air dried, preferably lyophilized.

The extract defined herein is characterized in that the crude extract of yacon, polar solvent soluble extract or nonpolar solvent soluble extract.

The crude extract as defined herein includes water, including purified water, C ₁ to C ₄ lower alcohols or mixtures thereof, preferably extracts soluble in methanol or ethanol.

The polar solvent soluble extract as defined herein includes extracts soluble in water, methanol, ethanol, butanol or a solvent selected from them, preferably methanol or ethanol.

The nonpolar solvent soluble extract as defined herein includes extracts soluble in hexane, chloroform, methylene chloride, ethyl acetate, glycerin or butylene glycol, preferably hexane, chloroform or ethyl acetate.

Hyperlipidemia and atherosclerotic vascular diseases as defined herein include, in particular, cardiac diseases such as general hyperlipidemia, arteriosclerosis, heart failure, hypertensive heart disease, arrhythmia, congenital heart disease, myocardial infarction, angina pectoris and the like; As diseases including vascular diseases such as stroke and peripheral vascular diseases, there are preferably ischemic cardiovascular diseases, more preferably hyperlipidemia and arteriosclerosis.

Hereinafter, the method for obtaining the dry powder of the present invention and its extract will be described in detail.

The dry powder of the present invention is washed with water and washed with a power cutter after yacon tubers grown in Uljin, Gyeongbuk, and then -70 to -40 ℃ using a deep freezer (deep freezer, MDF-U32V, Sanyo, Japan), preferably After freezing at -60 to -50 ℃ for 12 to 36 hours, preferably 18 to 30 hours, using a freeze dryer (PVTFD500R, Ilsin Lab, Korea) 3.5 × 10 ^-1 bar, -70 to -40 ℃ , Freeze-dried so that the moisture content is about 5% for 24 to 48 hours, preferably 30 to 42 hours at -60 to -50 ℃, and then saw through a manufacturing process to grind it into 60 mesh (mesh) The dry powder of the invention can be obtained.

The crude extract of the present invention is pulverized dry powder obtained above, water, C ₁ to C ₄ lower alcohol or a mixed solvent thereof, preferably methanol or ethanol, about 0.3 to 2 times the sample weight, preferably as an extraction solvent. Preferably 0.5 to 0.8 times (w / v), and cold extraction, hot water extraction, ultrasonic extraction for 1 to 20 days, preferably 5 to 10 days at 5 to 70 ℃, preferably 10 to 50 ℃ , Reflux cooling extraction, heating extraction, and the like, preferably extracted by cold extraction method, followed by filtration and concentration of the filtrate under reduced pressure at a temperature of 30 ℃ or less to obtain the crude extract of the present invention.

In addition, the polar solvent or non-polar solvent soluble extract of the present invention is 1 to 5 times the weight, preferably 2 to 4 times the volume (v / v) of the crude extract obtained above, preferably the methanol or ethanol crude extract of yacon tuber ), And then, hexane, chloroform, ethyl acetate and butanol are sequentially added in the same volume with water, and fractionated 1 to 5 times, preferably 2 to 4 times, in a nonpolar solvent such as hexane, chloroform, ethyl acetate, and the like. Soluble nonpolar solvent soluble extract; And polar solvent soluble extracts soluble in polar solvents such as butanol and water.

The present invention provides a pharmaceutical composition for the prevention and treatment of hyperlipidemia and atherosclerotic vascular disease, comprising yacon dry powder obtained by the above production method or an extract thereof as an active ingredient.

The pharmaceutical composition containing the dry powder or extract thereof of the present invention comprises 0.1 to 50% by weight of the dry powder or extract thereof based on the total weight of the composition.

However, the composition as described above is not necessarily limited thereto, and may vary according to the condition of the patient and the type and extent of the disease.

Dry powder of the present invention or the extract itself is almost no toxicity and side effects, so it is a drug that can be used with confidence even for long-term administration for the purpose of prevention.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

The composition of the present invention can be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral formulations, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. Carriers, excipients and diluents that may be included in the composition comprising extracts include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, 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, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the composition of the present invention is preferably administered at 0.5 g / kg to 5 g / kg, preferably 1 g / kg to 3 g / kg per day. The administration may be carried out once a day or divided into several doses. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.

The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

In addition, the present invention is yacon obtained by the above production method Provided is a health functional food for preventing and improving hyperlipidemia and atherosclerotic vascular disease, comprising a dry powder or an extract thereof as an active ingredient.

The composition comprising the dry powder of the present invention or extract thereof may be used in various applications, such as drugs, foods and beverages for the prevention and improvement of hyperlipidemia and atherosclerotic vascular disease. Examples of the food to which the dry powder or extract thereof may be added include various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, and are powders, granules, tablets, capsules or beverages. Available in form.

The amount of the dry powder or extract thereof in the food or beverage of the present invention is generally added to the health food composition of the present invention to 1 to 5% by weight of the total food weight, the health beverage composition is 0.02 to 100 ml based on 100 ml 10 g, preferably 0.3 to 1 g.

The health beverage composition of the present invention contains the dry powder or extract thereof of the yacon as an essential ingredient in the indicated ratio, and there are no particular limitations on the liquid component, and additional ingredients such as various flavors or natural carbohydrates, such as ordinary beverages, are included. It may contain as. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. have. The proportion of said natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g, per 100 mL of the composition of the present invention.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

Yacon dry powder of the present invention or extracts thereof has been found to have a blood lipid-lowering activity, an arterial wall atherosclerosis inhibitory activity and vascular smooth muscle cell proliferation inhibitory effect, useful pharmaceutical composition for the prevention and treatment of hyperlipidemia and atherosclerotic vascular disease And health functional foods.

Hereinafter, the present invention will be described in detail by reference examples, examples and experimental examples.

However, the following Reference Examples, Examples, and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Reference Examples, Examples, and Experimental Examples.

Example  One. Yacon  Preparation of Dry Powder

Yacon tubers grown in Uljin, Gyeongbuk, Korea, were purchased. 1 kg of yacon tubers were washed with water, chopped using a power cutter (M-102, Mirae Enterprise, Korea), and lyophilized. Freeze-drying was frozen for 24 hours at -55 ° C using a deep freezer (deep freezer, MDF-U32V, Sanyo, Japan), and then 3.5 × 10 ^-1 bar using a freeze-dryer (PVTFD500R, Ilsin Lab, Korea). , And dried at -55 ° C. for 36 hours to obtain a water content of about 5%. From this, 100 g of yacon dried product was obtained to obtain a yield of 10%, which was pulverized to 60 mesh to obtain a yacon dry powder, which was used as a sample of the following experimental example (hereinafter referred to as 'YC').

Example  2. Yacon Crude extract  Produce

2 kg of yacon dry powder of Example 1 was ground and put into 1.5L of methanol, and extracted at 22 ° C. for 6 days while shaking with a shaker (DS-300L, Dasol Science, Korea). After 6 days, the filtrate was concentrated under reduced pressure at a temperature of 30 ° C. or lower to obtain 75.9 g of a crude methanol extract, which was used as a sample of the following experimental example (hereinafter referred to as 'YC-M').

Example  3. Yacon Nonpolar Solvent  Preparation of Soluble Extracts

3-1. Yacon Hexane  Preparation of Extract

After 200 g of the crude extract of yacon of Example 2 was suspended in 500 mL of distilled water, poured into 2000 mL of fraction funnel, and then added with the same amount of hexane to shake well to separate the water and hexane layers. Repeat twice. Concentration, drying and drying under reduced pressure yielded 9.3 g of hexane extract of yacon (hereinafter referred to as 'YC-HE') and 65.2 g of a water-soluble fraction, which were used as samples in the following experimental example.

3-2. Yacon  Preparation of Chloroform Extract

The same procedure as in Example 3-1 was carried out except that 500 mL of the water-soluble fraction of Example 3-1 was added twice with 500 mL of chloroform to extract 14.5 g of chloroform extract of yacon (hereinafter, 'YC- C) and 50.3 g of a water-soluble fraction were obtained and used as a sample of the following experimental example.

3-3. Yacon  Preparation of ethyl acetate extract

The same process as in Example 3-1 was carried out except that 500 mL of ethyl acetate was added to 500 mL of the water-soluble fraction of Example 3-2, and extracted twice. 16.7 g of ethyl acetate extract of yacon (hereinafter, ' YC-E ') and 33.2 g of water-soluble fractions were obtained and used as samples in the following experimental example.

Example  4. Yacon  Preparation of Polar Solvent Soluble Extract

The same process as in Example 3-1 was carried out except that 500 mL of butanol was added twice to 500 mL of the water-soluble fraction of Example 3-3 to extract 19.2.g of yacon butanol (hereinafter, 'YC -B ') and 12.5 g of water-soluble fractions (hereinafter referred to as' YC-W') were obtained and used as samples in the following experimental example.

Reference Example  1. Preparation of experimental animals

1-1. Experimental animal

Experimental animals were allowed to adapt 50 New Zealand white rabbit males (Samtako, Korea) weighing 2 kg to the environment for two weeks, and then kept at a temperature of 23 ± 2 ℃ and a humidity of 55 to 60%. Was measured once a week at a certain time, and feed intake and drinking capacity were measured at the same time each day and calculated as daily intake by subtracting the remaining amount from the previous day's supply.

1-2. Experimental diet

Ten rabbits each prepared in Reference Example 1-1 (hereinafter referred to as 'NCD'), a high-cholesterol diet intake group (hereinafter referred to as 'HCD'), and a yacon low-dose ingestion group (hereinafter referred to as 'NCD') , The group called 'YC-L', the yacon high dose group (hereinafter referred to as 'YC-H') and the lovastatin group (positive control, hereinafter referred to as 'LVS'). Configured.

The rabbits of the other groups except the NCD group were fed cholesterol-containing high cholesterol diet for 4 weeks at 150 g weight per head per head for 4 weeks, causing hyperlipidemia of 920 to 955 mg / dL. The hyperlipidemia-induced rabbits were fed yacon low dose (0.5 g / kg / day), yacon high dose (2.5 g / kg / day) and lovastatin (0.002 g / kg / day) for 8 weeks.

Hereinafter, the dietary composition of the experimental diet for each experimental group will be described.

The NCD group was a comparative experiment group of the negative control group HCD and supplied the rabbit diet of Purina Co., Ltd. (Korea) as a basic diet. The nutritional value of the basic diet consists of 15.0% by weight crude protein, 2.0% by weight crude fat, 15.0% by weight crude fiber, 10.0% by weight ash, 1.2% by weight calcium, 0.5% by weight phosphorus. In contrast, the HCD group was ingested a high-cholesterol feed supplemented with 2% by weight of corn oil and 0.5% by weight of cholesterol as a negative control for 4 weeks. YC-L experimental group was ingested yacon dry powder of Example 1 for 8 weeks at a dose of 0.5 g / kg / day in the dietary composition of the HCD group, YC-H experimental group in the dietary composition of the HCD group Yacon dry powder of 1 was ingested for 8 weeks at a dose of 2.5 g / kg / day. Statin-based drugs are now widely used as drugs for treating hyperlipidemia. Therefore, the LVS group, the lovastatin intake group, was composed of the positive control group, and the LVS group was ingested lovastatin for 8 weeks at 0.002 g / kg / day, which is a general clinical use dose, in the dietary composition of the HCD experimental group.

Experimental Example  One. Rabbit  Blood Lipid Level Measurement

In order to confirm the blood lipid concentration lowering activity in vivo, that is, the experimental animal of the yacon dry powder prepared in Example 1, blood biochemical tests were performed.

Rabbits composed of the general diet intake group (NCD), high cholesterol diet intake group (HCD), yacon dry powder intake group (YC-L, YC-H) and lovastatin intake group (LVS) prepared in Reference Example 1-2. The ear arterial vessels were expanded with 70% ethanol and then bleeded so that the ratio of 3.8% sodium citrate and blood was 1: 6 from the ear artery using a 20 gauge syringe. The collected blood was centrifuged at 2500 rpm for 10 minutes (MF-300, Hanil, Co, LTD, Daejeon, Korea) to separate the plasma and stored at -20 ℃ until measured. Total cholesterol concentration, LDL (LDL) Concentration, echidiel (HDL) concentration and triglyceride concentration (triglyceride) concentration measurement was used.

1-1. Total Cholesterol Concentration

Total cholesterol concentration in the plasma by an enzymatic method using a cholesterol solution AM-202-K for measurement (Asan Pharmaceutical Co., Ltd., South Korea) [Anal. Biochem . , 142 , pp. 347-350, 1984].

 Plasma, reagent blanks, 20 μl each of the standard solution and 3 mL of the enzyme solution were mixed well and allowed to stand at 37 ° C. for 5 minutes, and then the absorbance was measured at a wavelength of 500 nm within 60 minutes. The total cholesterol content was obtained by multiplying the ratio of the sample absorbance to the standard solution absorbance by the standard solution concentration (300 mg / dL).

As shown in Table 1 and FIG. 1A, the total cholesterol concentration (936.25 ± 188.33 mg / dL) induced by 4 weeks of 0.5% high cholesterol diet was 1507.50 ± 332.02 mg / day by 8 weeks of sustained high cholesterol diet. The increase in dL blood total cholesterol concentration was shown. The total cholesterol level increased by this high cholesterol diet was reduced to 814.63 ± 198.55 and 516.25 ± 173.90 mg / dL level by 8 weeks of 0.5 and 2.5 g / kg / day intake of yacon dry powder, respectively. Decreased to 549.17 ± 171.06 mg / dL. Therefore, in the low-dose yacon dry powder intake group (YC-L), the increase in total cholesterol in blood was suppressed by 8 weeks of continuous high-cholesterol diet intake, and in the high-dose yacon dry powder intake group (YC-H) It was confirmed that blood cholesterol lowering activity similar to or better than lovastatin, which is widely known as a drug for treating hyperlipidemia.

Experimental group Total cholesterol in blood (mg / dL) 0 weeks 2 weeks 4 weeks 6 Weeks 8 Weeks General Dietary Group (NCD) 33.56 ± 3.51 34.33 ± 2.90 32.67 ± 3.84 32.35 ± 1.33 32.66 ± 2.33 Cholesterol Dietary Group (HCD) 936.25 ± 188.33 1008.75 ± 126.08 1143.75 ± 210.09 1310.00 ± 234.74 1507.50 ± 332.02 Cholesterol diet + low dose yacon intake group (0.5 g / kg / day) 951.35 ± 198.16 921.00 ± 111.24 834.52 ± 207.93 837.32 ± 194.72 814.63 ± 198.55 Cholesterol diet + high dose yacon intake group (2.5 g / kg / day) 926.54 ± 197.42 894.35 ± 170.12 730.35 ± 196.86 638.56 ± 134.09 * 516.25 ± 173.90 ** Cholesterol diet + lovastatin intake group (2 mg / kg / day) 943.25 ± 165.48 854.19 ± 168.98 712.37 ± 125.07 650.92 ± 129.12 * 549.17 ± 171.06 ** ** The total cholesterol concentration (mg / dL) result was expressed as the mean ± standard error value for 10 samples in each group, and the significance test was performed by ONE WAY ANOVA Dunnett's Test for each experimental group for the cholesterol diet group. * P <0.05 and ** P <0.01.

1-2. Triglyceride  Concentration measurement

Triglyceride concentration in blood plasma is the enzyme used for the Asan set triglyceride measurement solution AM 157S-K (Asan Pharmaceutical Co., Ltd., South Korea) methods [Clin. Chem . , 21 , pp. 437-441, 1975.

20 μl of plasma, reagent blank, standard solution, and 3 mL of enzyme solution were mixed well and left at 37 ° C. for 10 minutes, and then the absorbance was measured at a wavelength of 550 nm within 60 minutes in contrast to the reagent blank. The triglyceride concentration was obtained by multiplying the ratio of the sample absorbance to the standard solution absorbance by the standard solution concentration (300 mg / dL).

As shown in Table 2 and FIG. 1B, blood triglyceride concentrations (82.60 ± 12.05 mg / dL) induced with a 0.5% high cholesterol diet for 4 weeks were 145.68 ± 8.15 mg / dL for a subsequent 8 weeks sustained high cholesterol diet. An increase in triglyceride concentration in blood was shown. The triglyceride concentration increased by high cholesterol diet decreased to 68.95 ± 9.33 and 32.15 ± 6.32 mg / dL levels by yacon dry powder 0.5 and 2.5 g / kg / day intake for 8 weeks, respectively. Decreased to 34.54 ± 5.26 mg / dL. Therefore, in the low-dose yacon dry powder intake group (YC-L), the increase in blood triglycerides caused by 8 weeks of continuous high-cholesterol diet intake was suppressed, and in the high-dose yacon dry powder intake group (YC-H) The blood triglyceride concentration lowering activity similar to lovastatin, widely known as a drug for treating hyperlipidemia, was confirmed.

Experimental group Blood Triglycerides (mg / dL) 0 weeks 2 weeks 4 weeks 6 Weeks 8 Weeks General Dietary Group (NCD) 24.65 ± 4.13 22.35 ± 3.44 23.65 ± 3.40 25.62 ± 2.17 24.32 ± 1.55 Cholesterol Dietary Group (HCD) 82.60 ± 12.05 94.56 ± 3.44 125.62 ± 5.63 130.59 ± 9.20 145.68 ± 8.15 Cholesterol diet + low dose yacon intake group (0.5 g / kg / day) 78.65 ± 6.32 84.56 ± 7.51 85.62 ± 5.65 ** 78.65 ± 8.56 ** 68.95 ± 9.33 ** Cholesterol diet + high dose yacon intake group (2.5 g / kg / day) 83.00 ± 6.34 72.03 ± 6.58 * 54.32 ± 5.61 ** 34.12 ± 7.85 ** 32.15 ± 6.32 ** Cholesterol diet + lovastatin intake group (2 mg / kg / day) 78.62 ± 11.32 65.12 ± 6.44 ** 43.16 ± 4.56 ** 38.15 ± 6.32 ** 34.54 ± 5.26 ** Serum triglyceride concentration (mg / dL) result was expressed as mean ± standard error value for 10 samples in each group, and significance evaluation was obtained by performing ONE WAY ANOVA Dunnett's Test for each experimental group on cholesterol diet group. P <0.05 and ** P <0.01.

1-3. Equdiel  And ELDEL  Concentration measurement

The concentration of Echidiel (HDL) in the plasma was precipitated β-lipoprotein (LDL, VLDL) by using Echidiel Colletase AM 203-K (Asan Pharmaceutical Co., Ltd.), and then the cholesterol of HDL in the supernatant was tested. It calculated | required by the enzymatic method as an example. The plasma and 0.2 mL of the separation solution were mixed well and left at room temperature for 10 minutes, followed by centrifugation at 3000 rpm for 10 minutes. 3 mL of enzyme solution was mixed well with each 0.1 mL of the supernatant, reagent blank, and standard solution, which was allowed to stand at 37 ° C. for 5 minutes. The absorbance was measured at 500 nm with the reagent blank as a control. The HDL concentration was obtained by multiplying the ratio of the sample absorbance to the absorbance of the standard solution by the standard solution concentration (50 mg / dL) and the dilution factor 2. The concentration of LDL (LDL) was calculated by Equation 1 [ Clin . Chem . , 18 , pp. 499-502, 1972.

LDL = Total Plasma Cholesterol-HDL-Triglycerides / 5

HDL transports and removes unnecessary cholesterol. As shown in Table 3 and Figure 3, the high cholesterol diet group slightly increased the HDL concentration in the blood compared to the normal diet group, which is considered to be a defense effect in vivo by the high cholesterol diet, showing a positive effect only Was not observed and gradually decreased at 8 weeks.

As shown in Table 3 and FIG. 1C, blood HDL concentrations were increased to 32.62 ± 5.02 and 36.48 ± 3.41 mg / dL levels by 8 weeks of yacon dry powder 0.5 and 2.5 g / kg / day intake, respectively. The lovastatin group increased to 40.12 ± 3.39 mg / dL. Increased HDL levels than high cholesterol diets indicate that yacon dry powder may lower blood cholesterol levels.

As shown in Table 4 and FIG. 1D, the blood LDL concentration (378.41 ± 81.21 mg / dL) induced by the 4 weeks of 0.5% high cholesterol diet was 483.19 ± 116.73 mg / dL by the subsequent 8 weeks of continuous high cholesterol diet. Increased in blood LDL concentrations. The increased LDL concentration in these high cholesterol diets was reduced to 313.65 ± 60.24 and 178.65 ± 48.65 mg / dL levels by 8 weeks of ingestion of 0.5 and 2.5 g / kg / day of yacon dry powder, respectively. Decreased to ± 57.17 mg / dL. Therefore, in the low-dose yacon dry powder intake group (YC-L), the increase in blood LDL caused by 8 weeks of continuous high-cholesterol diet intake was suppressed. It was confirmed that blood LDL concentration lowering activity was similar or better than that of lovastatin, which is widely known as a therapeutic drug. Since LDL is a modified form of LDL cholesterol, which easily sticks to the walls of blood vessels and causes atherosclerosis, a decrease in LDL means a decrease in the deposition of cholesterol in the blood.

Experimental group Blood Equedel (mg / dL) 0 weeks 2 weeks 4 weeks 6 Weeks 8 Weeks General Dietary Group (NCD) 21.00 ± 3.18 21.25 ± 3.75 20.75 ± 3.92 22.00 ± 3.08 21.75 ± 4.21 Cholesterol Dietary Group (HCD) 21.60 ± 2.44 27.00 ± 4.01 28.40 ± 5.93 31.65 ± 5.65 29.87 ± 4.71 Cholesterol diet + low dose yacon intake group (0.5 g / kg / day) 22.14 ± 2.54 26.81 ± 3.14 27.81 ± 2.97 29.65 ± 3.41 32.62 ± 5.02 Cholesterol diet + high dose yacon intake group (2.5 g / kg / day) 24.02 ± 3.59 25.64 ± 3.61 29.84 ± 2.68 32.40 ± 3.94 36.48 ± 3.41 Cholesterol diet + lovastatin intake group (2 mg / kg / day) 23.61 ± 3.59 33.80 ± 5.29 35.61 ± 4.83 37.84 ± 4.29 40.12 ± 3.39 The results of blood Echidiel concentration (mg / dL) were expressed as the mean ± standard error value of 10 samples in each group, and the significance evaluation was obtained by performing the ONE WAY ANOVA Dunnett's Test for each experimental group for the cholesterol diet group. P <0.05 and ** P <0.01.

Experimental group LDL in the blood (mg / dL) 0 weeks 2 weeks 4 weeks 6 Weeks 8 Weeks General Dietary Group (NCD)  13.51 ± 3.45 14.00 ± 3.67 15.50 ± 3.96 14.56 ± 2.10 15.34 ± 2.54 Cholesterol Dietary Group (HCD) 378.41 ± 81.21 403.62 ± 68.00 409.20 ± 93.40 448.34 ± 83.13 483.19 ± 116.73 Cholesterol diet + low dose yacon intake group (0.5 g / kg / day) 368.56 ± 62.1 384.61 ± 79.03 375.21 ± 46.58 321.61 ± 51.23 313.65 ± 60.24 Cholesterol diet + high dose yacon intake group (2.5 g / kg / day) 349.65 ± 58.62 312.35 ± 61.23 236.95 ± 49.65 195.63 ± 51.25 ** 178.65 ± 48.65 ** Cholesterol diet + lovastatin intake group (2 mg / kg / day) 335.64 ± 66.83 331.91 ± 63.19 280.17 ± 50.42 220.64 ± 46.90 * 210.36 ± 57.17 * Blood Elield concentration (mg / dL) results were expressed as mean ± standard error value for 10 samples in each group, and significance evaluation was obtained by ONE WAY ANOVA Dunnett's Test for each experimental group for cholesterol diet group. P <0.05 and ** P <0.01.

Experimental Example  2. Rabbit Of the aortic wall Atheromatous formation  observe

In order to confirm the aortic wall atherosclerosis (lipid deposition) lowering activity in vivo of the yacon dry powder prepared in Example 1, ie, experimental animals, fat staining was performed by applying the method disclosed in the literature as follows. (Gordon et al., 1988, Kim et al., 2000, Kobayashi et al., 2004).

Rabbits composed of the general diet intake group (NCD), high cholesterol diet intake group (HCD), yacon dry powder intake group (YC-L, YC-H) and lovastatin intake group (LVS) prepared in Reference Example 1-2. The rats were fasted 1 day after the last feeding of the test mixture mixed with the test substance, and an autopsy was performed the next day. Autopsy during sol retil ^{(zoletil ®; 50, Virbac,} France) to anesthetized by injection into the ear vein, and harvesting the aorta, including the arterial arch out from the heart by about 8 cm to form the width of the atheroma (atheroma) formed in the aortic wall Unfolded and fixed for measurement. In the fixed aorta, 5 cm or less at the base of the aortic arch, which can confirm the formation and relaxation of the atherosclerosis by cholesterol diet and test substance administration, was observed and compared after staining fat with a Sudan IV solution.

As shown in Table 5 and FIG. 2, quantitative comparison of atheromatous formations (FIG. 2A) and atheromatous formation rate (FIG. 2B) observed at the inner wall of the aorta about 5 cm long below the base of the aortic arch extracted at necropsy (FIG. 2B). In the high-cholesterol diet group, more than 60% of the atherosclerosis was formed in the inner wall, and the lovastatin-administered group was about 40%, and the inhibition of atherosclerosis was observed. A weak inhibitory effect of about 17% was observed in the 0.5 g / kg / day yacon dry powder intake group (YC-L), but about 35% in the 2.5 g / kg / day yacon dry powder intake group (YC-H). Inhibitory effect of atherosclerosis was similar to that of the lovastatin intake group, indicating that the formation of intraaortic atherosclerosis was significantly superior to the high cholesterol diet group.

Experimental group Intraaortic Atheromatous Formation Atheromatous formation rate (% area) Inhibition Rate (%) General Dietary Group (NCD) 1.07 ± 0.60 - Cholesterol Dietary Group (HCD) 61.62 ± 5.52 - Cholesterol diet + low dose yacon intake group (0.5 g / kg / day) 50.77 ± 4.88 17.61 ± 2.08 ** Cholesterol diet + high dose yacon intake group (2.5 g / kg / day) 39.85 ± 2.19 35.32 ± 1.95 ** Cholesterol diet + lovastatin intake group (2 mg / kg / day) 37.18 ± 4.05 39.66 ± 3.09 ** Intra-aortic atherosclerosis (% area) was expressed as mean ± standard error values for 10 samples per group, and inhibition was expressed as percent inhibition of each experimental group relative to the cholesterol diet. Significance evaluation was obtained by performing the ONE WAY ANOVA Dunnett's Test for each experimental group for the cholesterol diet group, and marked ** P <0.01.

Through the results of Experimental Examples 1 and 2, yacon freeze-dried powder is known to be a major factor in atherosclerotic vascular disease, and the improvement of hyperlipidemia and the formation of arterial wall atherosclerosis are achieved through lowering lipid concentration and inhibiting lipid deposition in the aorta. The inhibitory activity effect could be confirmed.

Experimental Example  3. Yacon  Rat of extract Arterial smooth muscle cell  Proliferation inhibitory activity measurement

In order to confirm the cell proliferation inhibitory activity of the yacon extract obtained in Examples 2 to 4 in vitro, vascular smooth muscle cells isolated from rat arteries, J. Pharmacol . Exp . Ther . , 317 , pp. 627-634, 2006, using the method described in the following.

The inhibition of cell proliferation of yacon crude extracts and fractions on rat arterial smooth muscle cell proliferation was measured by the number of smooth muscle cells and the incorporation rate of [ ³ H] thymidine in DNA.

3-1. Cell count measurement

For cell counting, rat arterial smooth muscle cells were seeded at 1 × 10 ⁵ cells / mL in a 12-well culture plate and had 10% bovine serum (FBS, fetal bovine serum, Gibco-BRL, USA). Incubated in DM culture medium (Dulbecco's modified Eagle's medium, Gibco-BRL, USA) for 24 hours at 37 ℃ in cell culture (MCO-18M, Sanyo, Japan) under 5% carbon dioxide conditions. The cells were then extracted with yacon methanol crude extract (YC-M), hexane extract (YC-HE), chloroform extract (YC-C), ethyl acetate extract (YC-E), butanol extract (YC-B) and water soluble fraction. (YC-W) was incubated with serum free medium (Gibco, BRL, USA) containing 0, 25, 50 and 100 μg / mL, respectively.

After 24 hours, cells were stimulated with 50 ng / mL platelet derived growth factor-BB (PDGF-BB, R & D System, USA), and after 24 hours of incubation, hemocytometer (Superior, MARIENFELD) , Germany). The cell number results are shown in Table 6 and FIG. 3. In FIG. 3, PDGF-BB was not treated as “PDGF-BB (−)” and treated as “PDGF-BB (+)”.

As shown in Table 6 and FIG. 3, when mouse arterial smooth muscle cell proliferation was induced with 50 ng / mL PDGF-BB, the number of cells in the general control group not treated with PDGF-BB (5.49 × 10 ⁴ cells / mL) The number of cells increased by 3 times (16.29 × 10 ⁴ cells / mL). The increase in cell number induced by PDGF-BB was inhibited at 3.15, 15.46 and 19.44% inhibition by yacon methanol crude extract (YC-M) concentrations of 25, 50 and 100 μg / mL, respectively. Hexane extract (YC-HE) 25, 50 and 100 [mu] g / mL concentration treatment inhibited at 3.42, 17.31 and 38.98% inhibition, respectively. Chloroform extract (YC-C) was inhibited with inhibition rates of 45.09, 78.24 and 92.59% by 25, 50 and 100 μg / mL concentration treatment, respectively. Ethyl acetate extracts (YC-E) were inhibited with inhibition rates of 38.88, 53.98 and 83.24%, respectively. Butanol extract (YC-B) was inhibited at concentrations of 4.62, 26.94 and 52.50% by treatment at 25, 50 and 100 μg / mL concentrations, respectively. Water soluble fractions (YC-W) were inhibited with inhibition rates of 2.87, 5.61 and 10.61% by 25, 50 and 100 μg / mL concentration treatments, respectively.

Therefore, it was confirmed that PDGF-BB induced rat arterial smooth muscle cell number was effectively inhibited by yacon crude extract and solvent fraction, and especially arterial smooth muscle cell having excellent chloroform extract (YC-C) and ethyl acetate extract (YC-E). It could be confirmed that the number increase inhibition effect.

sample Concentration (㎍ / mL) Cell count (× 10 ⁴ cell / mL) Inhibition Rate (%) Untreated control (0.1% DMSO)  5.49 ± 0.56 - PDGF-BB treatment group (50 ng / mL) 16.29 ± 1.05 - PDGF-BB + YC-M treatment group 25 50 100 15.96 ± 0.68 14.62 ± 1.09 14.19 ± 0.84  3.15 ± 1.64 ** 15.46 ± 1.56 ** 19.44 ± 1.95 ** PDGF-BB + YC-HE Treatment Group 25 50 100 15.92 ± 1.31 14.42 ± 0.85 12.08 ± 0.91  3.42 ± 1.91 ** 17.31 ± 2.09 ** 38.98 ± 0.95 ** PDGF-BB + YC-C treatment group 25 50 100 11.42 ± 1.04 7.84 ± 0.68 6.29 ± 0.74 45.09 ± 1.36 ** 78.24 ± 1.81 ** 92.59 ± 0.86 ** PDGF-BB + YC-E Treatment Group 25 50 100 12.09 ± 0.96 10.46 ± 0.68 7.30 ± 0.49 38.88 ± 2.09 ** 53.98 ± 1.81 ** 83.24 ± 2.10 ** PDGF-BB + YC-B treatment group 25 50 100 15.79 ± 1.10 13.38 ± 0.69 10.62 ± 0.75  4.62 ± 2.31 ** 26.94 ± 1.38 ** 52.50 ± 1.98 ** PDGF-BB + YC-W treatment group 25 50 100 15.98 ± 0.98 15.36 ± 0.85 14.28 ± 0.68  2.87 ± 0.84 ** 5.61 ± 1.32 ** 10.61 ± 2.14 ** Rat arterial smooth muscle cell count was expressed as mean ± standard error value for 6 samples in each group, and cell proliferation inhibition rate was expressed as% inhibition of each experimental group for PDGF-BB (50 ng / mL) treatment group. Significance evaluation was obtained by performing ONE WAY ANOVA Dunnett's Test for each experimental group for PDGF-BB treatment group and indicated as * P <0.05 and ** P <0.01.

3-2. Intracellular DNA  Synthetic Analysis

Intracellular DNA synthesis was determined by measuring the incorporation rate of [ ³ H] thymidine into intracellular DNA.

DM art with 10% bovine serum (FBS, fetal bovine serum, Gibco-BRL, USA) by receiving rat arterial smooth muscle cells under the same conditions as in the case of measuring the cell number of Experiment 3-1 in a 24-well culture plate The cultures (Dulbecco's modified Eagle's medium, Gibco-BRL, USA) were incubated at 37 ° C. for 24 hours in a cell incubator (MCO-18M, Sanyo, Japan) under 5% carbon dioxide conditions. The cells were then extracted with yacon methanol crude extract (YC-M), hexane extract (YC-HE), chloroform extract (YC-C), ethyl acetate extract (YC-E), butanol extract (YC-B) and water soluble fraction. (YC-W) was incubated with serum free medium containing 0, 25, 50 and 100 μg / mL, respectively.

After 24 hours cells were stimulated with 50 ng / mL PDGF-BB and treated with 2 μCi / mL of [ ³ H] thymidine. After 4 hours, the medium was aspirated to terminate the labeling reaction, and the culture medium was phosphate-buffered saline (PBS) containing 10% trichloroacetic acid and ethanol / ether (1: 1 by volume). ). Acid insoluble [ ³ H] thymidine is extracted with 300 μl of 0.5 M sodium hydroxide (NaOH) solution per well, and the solution is mixed with 3 mL of scintillation cocktail (Ultimagold, Packard Bioscience, USA) to provide a liquid scintillation counter (Scintillation). model LS3801, Beckman, Germany). The incorporation rate of [ ³ H] thymidine into cellular DNA is shown in Table 7 and FIG. 4. In FIG. 4, PDGF-BB was not treated as “PDGF-BB (−)” and treated as “PDGF-BB (+)”.

Table 7 and when induced rat arterial smooth muscle cell proliferation with 50 ng / mL PDGF-BB as shown in Figure 4, ^[3 H] of the normal control group not treated with PDGF-BB thymidine DNA mixing ratio (3292.52 cpm / 7.5 times higher [ ³ H] thymidine DNA incorporation (24850.56 cpm / well). This increase in PDGF-BB-induced [ ³ H] thymidine DNA incorporation was inhibited by inhibition of 0.74, 7.35 and 19.56% by yacon methanol crude extract (YC-M) concentrations of 25, 50 and 100 μg / mL, respectively. It became. Hexane extract (YC-HE) was inhibited at concentrations of 5.45, 9.25 and 24.39% by treatment at 25, 50 and 100 μg / mL concentrations, respectively. Chloroform extract (YC-C) was inhibited at concentrations of 40.76, 74.14 and 99.46% by treatment at 25, 50 and 100 μg / mL concentrations, respectively. Ethyl acetate extract (YC-E) was inhibited at 28.85, 51.94 and 82.74% by treatment at 25, 50 and 100 μg / mL concentrations, respectively. Butanol extract (YC-B) was inhibited with inhibition rates of 8.12, 33.48 and 57.74% by treatment at 25, 50 and 100 μg / mL concentrations, respectively. Water soluble fractions (YC-W) were inhibited at concentrations of 3.32, 4.01 and 10.16% by treatment of 25, 50 and 100 μg / mL concentrations, respectively.

Therefore, it was confirmed that DNA synthesis of PDGF-BB-induced rat arterial smooth muscle cells was effectively inhibited by crude extracts of Yacon and solvent fractions. Especially, chloroform extract (YC-C) and ethyl acetate extract (YC-E) were excellent arteries. It was confirmed that it exhibits an inhibitory effect on the increase of smooth muscle cell DNA synthesis.

Through the results of Experimental Examples 3-1 and 3-2, yacon crude extract and solvent extract showed excellent proliferation through inhibiting cell number increase and DNA synthesis inhibitory activity against arterial smooth muscle cells known as major factors of atherosclerotic vascular disease. It was confirmed that it exhibits inhibitory activity.

sample Concentration (㎍ / mL) [ ³ H] thymidine incorporation (cpm / well) Inhibition Rate (%) Untreated control (0.1% DMSO)  3292.52 ± 128.62 - PDGF-BB treatment group (50 ng / mL) 24850.56 ± 745.65 - PDGF-BB + YC-M treatment group 25 50 100 24690.62 ± 462.32 23 265.84 ± 692.51 20632.96 ± 451.32  0.74 ± 1.09 ** 7.35 ± 2.31 ** 19.56 ± 1.09 ** PDGF-BB + YC-HE Treatment Group 25 50 100 23675.35 ± 512.82 22854.94 ± 462.91 19591.82 ± 463.25  5.45 ± 1.68 ** 9.25 ± 2.19 ** 24.39 ± 3.06 ** PDGF-BB + YC-C treatment group 25 50 100 16062.69 ± 497.62 8866.09 ± 525.61 3406.91 ± 416.32 40.76 ± 2.63 ** 74.14 ± 1.98 ** 99.46 ± 0.86 ** PDGF-BB + YC-E Treatment Group 25 50 100 18629.94 ± 512.08 13651.82 ± 463.08 7012.05 ± 398.08 28.85 ± 1.98 ** 51.94 ± 2.10 ** 82.74 ± 1.92 ** PDGF-BB + YC-B treatment group 25 50 100 23098.65 ± 623.09 17631.82 ± 398.69 12397.61 ± 432.08  8.12 ± 1.68 ** 33.48 ± 2.65 ** 57.74 ± 1.81 ** PDGF-BB + YC-W treatment group 25 50 100 24 132.95 ± 526.34 23985.94 ± 451.09 22 658.98 ± 663.02  3.32 ± 1.06 ** 4.01 ± 0.96 ** 10.16 ± 2.61 ** The murine smooth muscle cell diene [ ³ H] thymidine incorporation was expressed as the mean ± standard error value for 6 samples in each group, and the inhibition rate was% of each experimental group for PDGF-BB (50 ng / mL) treatment group. ). Significance evaluation was obtained by performing ONE WAY ANOVA Dunnett's Test for each experimental group for PDGF-BB treatment group and indicated as * P <0.05 and ** P <0.01.

Hereinafter, the preparation examples of the composition comprising the yacon dry powder or extract of the present invention will be described, but the present invention is not intended to be limited thereto, but is intended to be described in detail.

Formulation example  One. Powder  Produce

YC-M 20 mg

Lactose 100 mg

Talc 10 mg

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

Formulation example  2. Preparation of Tablets

YC-HE 10 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components and tableting according to the conventional tablet manufacturing method to prepare a tablet.

Formulation example  3. Manufacture of capsule

YC-C 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

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

Formulation example  4. Preparation of injections

YC-E 10 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na2HPO4,12H2O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation example  5. Liquid  Produce

YC-B 20 mg

10 g of isomerized sugar

5 g of mannitol

Purified water

After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding lemon flavor appropriately, mixing the above components, adding purified water, adjusting the whole to 100 ml by adding purified water, and then filling into a brown bottle. The solution is prepared by sterilization.

Formulation example  6. Manufacture of healthy food

YC-W 1000 mg

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinic Acid 1.7 mg

50 μg folic acid

Calcium Pantothenate 0.5mg

Mineral mixture quantity

Ferrous Sulfate 1.75 mg

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

15 mg of potassium phosphate monobasic

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

100 mg of calcium carbonate

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

Formulation example  7. Manufacture of health drinks

YC-W 1000 mg

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water was added to a total of 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, &Lt; / RTI &gt;

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

1 is a diagram showing the change in blood total cholesterol (A), triglycerides (B), echidiel (C) and ELD (D) concentration when yacon dry powder is ingested in hyperlipidemia-induced rabbit for 8 weeks,

Figure 2 is a diagram showing the visual observation (A) and quantitative quantitative comparison of the atherosclerosis rate (B) when ingested yacon dry powder in hyperlipidemia-induced rabbit for 8 weeks,

3 is a diagram showing the inhibitory activity of the yacon crude extract and solvent fractions on the increase in the number of rat arterial smooth muscle cells induced by platelet-derived growth factor-ratio (PDGF-BB) (YC-M: yacon methanol crude extract, YC -HE: yacon hexane extract, YC-C: yacon chloroform extract, YC-E: yacon ethyl acetate extract, YC-B: yacon butanol extract, YC-W: yacon water soluble fraction),

4 is a diagram showing the inhibitory activity of the yacon crude extract and the solvent fraction on the increase of DNA synthesis of rat arterial smooth muscle cells induced by platelet-derived growth factor-rB (PDGF-BB) (YC-M: yacon methanol crude extract , YC-HE: yacon hexane extract, YC-C: yacon chloroform extract, YC-E: yacon ethyl acetate extract, YC-B: yacon butanol extract, YC-W: yacon water soluble fraction).

Claims (10)

A pharmaceutical composition for preventing and treating hyperlipidemia and atherosclerotic vascular disease, comprising yacon dry powder or extract thereof as an active ingredient. The pharmaceutical composition according to claim 1, wherein the yacon dry powder or extract thereof is obtained from leaves, stems, or tubers of yacon. The pharmaceutical composition according to claim 1, wherein the dry powder is yacon dried, lyophilized or hot air dried. The pharmaceutical composition according to claim 1, wherein the extract is a crude extract of yacon, a polar solvent soluble extract, or a nonpolar solvent soluble extract. The pharmaceutical composition according to claim 4, wherein the crude extract is an extract available in a solvent selected from water including purified water, C ₁ to C ₄ lower alcohols, or a mixed solvent thereof. The pharmaceutical composition according to claim 4, wherein the polar solvent soluble extract is an extract soluble in a solvent selected from water, methanol, ethanol, butanol or a mixed solvent thereof. The pharmaceutical composition according to claim 4, wherein the nonpolar solvent soluble extract is an extract soluble in a solvent selected from hexane, chloroform, methylene chloride, ethyl acetate, glycerin or butylene glycol. According to claim 1, wherein the hyperlipidemic and atherosclerotic vascular disease is hyperlipidemia, arteriosclerosis, heart failure, hypertensive heart disease, arrhythmia, congenital heart disease, myocardial infarction, angina pectoris and the like; A pharmaceutical composition that is a vascular disease such as stroke or peripheral vascular disease. Health functional food for preventing and improving hyperlipidemia and atherosclerotic vascular disease, containing yacon dry powder or extract thereof as an active ingredient. 10. The dietary supplement of claim 9 which is a powder, granule, tablet, capsule or beverage.

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