KR20160064683A - Composition for preventing or improving metabolic syndrome containing Acetic acid 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester - Google Patents

Abstract

The present invention relates to a composition comprising Acetic acid 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester, for preventing or alleviating metabolic syndrome and, more specifically, to a pharmaceutical composition comprising the ingredient for providing effects in treating or preventing diabetes, high blood pressure, hyperlipidemia, and the like, or to a health food composition. The composition of the present invention can provide effects in preventing or alleviating metabolic syndrome. In addition, the composition can be variously used in food and pharmaceutical fields.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing or improving metabolic syndrome containing 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid. , 17-diene-12,14-diynyl ester}

The present invention relates to a process for the preparation of 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester, comprising 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid The present invention relates to a composition for preventing or ameliorating metabolic syndrome and, more particularly, to a composition for preventing or ameliorating diabetes, hypertension and hyperlipemia by containing 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid. ≪ / RTI > or a pharmaceutically acceptable salt thereof.

Due to changes in lifestyle and westernization of dietary habits, the problem of adult diseases arising from accumulation of body fat such as hyperlipemia, hypertension and atherosclerosis is serious, and obesity is mainly caused by overeating high fat and high protein foods.

The energy accumulated due to excessive intake of high-fat foods is stored in the form of triglycerides in adipose tissue. When the amount of surplus energy to be stored is not covered by fat tissue alone, energy is supplied to other tissues such as muscles and liver There are lipid dysregulation and lipotoxicity that are stored. In addition, fat stored in each tissue is transformed into free fatty acid through lipolysis, and it is known that this free fatty acid induces disabling of the insulin signal transduction system through signal transduction mechanisms such as JNK and PKC .

Inhibition of the insulin signaling system inevitably leads to insulin resistance, which in turn increases insulin secretion by compensating for nonfunctioning insulin. Over-secreted insulin increases the body's salinity, moisture and fat and stimulates the sympathetic nerves, resulting in increased heart rate and constriction of blood vessels, leading to obesity, elevated blood pressure, elevated blood pressure, and elevated blood lipid levels (low HDL cholesterol, high triglycerides) And also causes metabolic syndrome like diabetes.

In order to prevent the accumulation of lipids in the body, which is the cause of metabolic syndrome, it is necessary to regulate diet, but it is also true that it is difficult to practice it in real life. In addition, even if a slight weight loss, the risk of increasing the weight again due to the yo-yo phenomenon is high. Therefore, in order to maintain or reduce weight, it is necessary to make efforts and care for a long time.

For weight control, gauging therapy is needed to treat the disease through proper medication and physical exercise. The cost is the diet or diet control for weight loss or weight loss for the beauty of a man who wants to bloom or who wants to make his body slim. However, in many cases, in order to see the effect of weight loss in a short period of time, it is often seen that side effects are caused by taking a surgical treatment to inhale the fat of the body-specific region or taking a herbal medicine or a medicament.

Most of the obese patients are treated after the cause, so they are often after complications caused by obesity. In addition, since the treatment effect according to the symptom varies according to sex, age, socioeconomic status, or individual, it is more urgent for today's modern man to develop a cost-saving agent that combines prevention and treatment.

In recent years, attention has been focused on components extracted from ginseng, especially polyyne, as a component isolated from natural materials. Among them, paracinol, paraxidol, paraxyltriol and the like as polyacetylene components have cytotoxicity against cancer cells and thus have anticancer effects. However, studies on the polyacetylenic component are still insignificant, and remarkable research results have not been reported on the efficacy associated with the metabolic syndrome such as diabetes, hypertension, and hyperlipidemia in addition to the anticancer effect.

Accordingly, the present inventors have made intensive efforts to find a component capable of decomposing fat in the body and improving the overall health state of the body. As a result, it has been found that 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid Has been found to be effective in the prevention or treatment of metabolic diseases by decomposing triglyceride when the differentiated adipocytes are treated with differentiated fat cells, thus completing the present invention.

The present invention aims to provide a pharmaceutical composition and a health functional food composition capable of providing a preventive or ameliorative effect of metabolic syndrome such as diabetes, cardiovascular disease, obesity and hyperlipidemia.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or improving metabolic syndrome containing 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid as an active ingredient .

The present invention also provides a health functional food composition for preventing or improving metabolic syndrome containing 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid as an active ingredient.

The composition of the present invention can provide a preventive or ameliorative effect of metabolic syndrome by containing 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid as an active ingredient, Can be used in various fields.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a graph showing the results of measuring lipid-degrading activity of 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid.
2 is a graph showing changes in body weight following administration of 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid.
Figure 3 is a graph showing the effect of 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid on lipolysis promotion.
FIG. 4 is a graph showing the effect of increasing the expression of CPT-1 in liver tissues upon administration of 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is well known and commonly used in the art.

The present invention relates to a composition for preventing or improving metabolic syndrome comprising 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid represented by the following formula 1 as an active ingredient.

[Chemical Formula 1]

In the present invention, the active ingredient may be characterized by decomposing triglycerides and preventing or ameliorating the metabolic syndrome such as diabetes, cardiovascular disease, obesity, or hyperlipidemia.

The composition for preventing or improving metabolic syndrome of the present invention is useful as a preventive or ameliorating agent for metabolic syndrome such as diabetes mellitus, obesity, hyperlipidemia such as hypertension, arteriosclerosis, stroke, cerebral hemorrhage, angina pectoris and myocardial infarction, And is also effective in improving the immune system.

In addition, the composition for preventing or improving metabolic syndrome of the present invention is effective for prevention of platelet aggregation, prevention of thrombus formation, inhibition of vasoconstriction and / or inhibition of cholesterol, thereby alleviating or treating vascular diseases. Specifically, the composition of the present invention can be used for improving blood circulation due to antithrombotic effect, and is effective for prevention of vascular diseases including obesity, diabetes and hyperlipemia, relieving symptoms or treating. Such vascular diseases include, for example, obesity, diabetes, stroke, cerebral hemorrhage, arteriosclerosis, angina pectoris, myocardial infarction, hypertension, anemia, migraine or hyperlipemia.

In addition, the composition for preventing or ameliorating metabolic syndrome of the present invention has an effect to enhance immunity, can help to relieve fatigue, and has an excellent effect for mental fatigue recovery or physical fatigue recovery. It can also help improve learning ability by improving memory, concentration or cognitive ability.

In the present invention, the active ingredient may be contained in an amount of 0.001 to 50% by weight, preferably 0.01 to 30% by weight, more preferably 0.1 to 10% by weight, By weight. If the content of the 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid is less than 0.001% by weight, Or there is a problem of the shape.

The composition of the present invention is not particularly limited in its formulation, but may be, for example, a pharmaceutical composition or a health functional food composition.

In the present invention, when the composition is a pharmaceutical composition, it may be characterized by comprising at least one pharmaceutically acceptable carrier or excipient.

The pharmaceutical composition according to the present invention may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, and the like, and includes 16-hydroxy-octadeca- , 14-dienyl ester acetic acid as an active ingredient may be added to form an oral or parenteral preparation in the form of solid, semi-solid or liquid.

When the pharmaceutical composition according to the present invention is orally administered, it may be administered orally in the form of powders, granules, tablets, pills, capsules, fine granules, powders, pellets, suspensions, emulsions, And can be used as formulations. When the composition of the present invention is administered parenterally, it may be formulated into injections, drops, ointments, lotions, sprays, suspensions, emulsions, suppositories, and the like. The active ingredient of the present invention can be easily formulated according to a conventional method, and a surfactant, an excipient, a coloring agent, a spice, a preservative, a stabilizer, a buffer, a suspending agent and other auxiliaries to be used can be suitably used.

In addition, one or more of the following additives may be added to the composition, if necessary, in combination. As the additive, for example, grape juice such as grapefruit, apple, orange, lemon, pineapple, banana, and pear (may be concentrated juice, powdered juice, etc.); Vitamins such as palmitic acid retinol, riboflavin, pyridoxine, cyanocobalamine, sodium ascorbate, nicotinamide, calcium pantothenate, folic acid, biotin, cholecalciferol, - water-soluble and fat-soluble vitamins such as carotene); Spices (such as lemon flavor, orange flavor, strawberry flavor, grapefruit flavor or vanilla essence); Amino acids, nucleic acids and salts thereof (glutamic acid, sodium glutamate, glycine, alanine, aspartic acid, sodium aspartate, inosine, etc.); Vegetable fibers (polydextrose, pectin, xanthan gum, glucomannan or alginic acid and the like); Or minerals such as sodium chloride, sodium acetate, magnesium sulfate, potassium chloride, magnesium chloride, magnesium carbonate, calcium chloride, dipotassium phosphate, sodium phosphate, calcium glycerophosphate, sodium ferrous citrate, iron citrate, Copper sulfate, sodium iodide, potassium sorbate, zinc, manganese, copper, iodine or cobalt), and the like.

The composition may further contain a preservative, a stabilizer, a wetting agent or an emulsifying accelerator, a pharmaceutical adjuvant such as a salt and / or a buffer for controlling osmotic pressure, and other therapeutically useful substances, . ≪ / RTI >

Examples of formulations for oral administration include tablets, pills, hard and soft capsules, liquids, suspensions, emulsions, syrups, granules and the like. These formulations may contain a whitening agent (e.g., lactose, dextrose, Sucrose, mannitol, sorbitol, cellulose and glycine), lubricants (such as silica, talc, stearic acid and magnesium or calcium salts thereof and polyethylene glycols). The tablets may further contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally mixed with starch, agar, alginic acid or its sodium salt Such as disintegrants, absorbents, coloring agents, flavoring agents, and sweetening agents. Tablets can be prepared by conventional mixing, granulating or coating methods.

Further, in the present invention, when the composition is a health functional food composition, it may be further characterized as comprising a pharmaceutical acceptable excipient in the form of a food or an edible beverage.

For example, it can be formulated into various foods, beverages, gums, tea vitamin complexes, health functional foods, and various food additives. Since the 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid used in the present invention has little toxicity and side effects, it can be safely used for prolonged use even for prophylactic purposes.

The health functional food composition of the present invention has no particular limitation on other ingredients other than those containing 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid as an essential ingredient in the indicated ratios, And may contain various flavors or natural carbohydrates as an additional ingredient. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. As natural flavors other than those described above, natural flavors (such as tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin)) and synthetic flavors (saccharin, aspartame, etc.) have. The ratio of the natural carbohydrate is not limited thereto, but 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, the health functional food composition of the present invention may contain other components or the like which can give synergy to the main effect within a range not impairing the intended main effect of the present invention. For example, additives such as perfume, coloring agent, bactericide, antioxidant, preservative, moisturizing agent, thickening agent, inorganic salt, emulsifier and synthetic polymer substance may be further added for improvement of physical properties. In addition, it may further contain auxiliary components such as water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymeric polysaccharides and seaweed extract. The above components may be mixed and selected without difficulty by those skilled in the art depending on the purpose of formulation or use, and the amount thereof may be selected within a range that does not impair the objects and effects of the present invention. For example, the addition amount of the above components may be in the range of 0.01 to 5% by weight, more specifically 0.01 to 3% by weight based on the total weight of the composition.

In addition to the above, the health functional food composition of the present invention can be used as a nutritional supplement, a vitamin, a mineral (electrolyte), a flavoring agent such as a synthetic flavoring agent and a natural flavoring agent, a coloring agent and a thickening agent (cheese, chocolate, Alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, carbonating agents used in alcohol or carbonated drinks, and the like. In addition, the health functional food composition of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so important, but is generally selected in the range of 0 to 20% by weight based on the total weight of the composition of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for illustrating the present invention and that the scope of the present invention is not construed as being limited by these embodiments. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

[ Reference example  One]

The 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid used to test the efficacy of the composition of the present invention was purchased from COSVISION (Korea).

[ Test Example  1] Toxicity experiment

≪ Oral administration >

ICR mouse and Sprague Dawley (Daegu Hyochang Science) were divided into two groups of 10 mice each, and in one group, 16-hydroxy-octadec-9,17-dien-12,14- Dienyl ester acetic acid was orally administered at a dose of 200 mg / kg, and the other group was not administered with 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid. After 2 weeks of toxicity, no deaths occurred in both groups, and no symptoms were observed except for the control group.

<Peritoneal administration>

10 mice of the ICR mice (25 ± 5 g) and Sprague Dawley (Daegu Hyochang Science) were divided into two groups of 16-hydroxy-octadeca-9,17-dien-12, 14-dienyl ester acetic acid was administered intraperitoneally at a dose of 20 mg / kg. After 24 hours of toxicity, no deaths occurred in all of the 2 groups. No apparent symptoms were observed in the control group. From the above results, it was confirmed that the extract of the present invention had almost no acute toxicity.

[ Test Example  2] Neutral fat resolution at the treatment of differentiated adipocytes

1. Adipocyte culture and induction of differentiation

In the medium supplemented with 10% calf serum (bovine calf serum, Gibco co. USA) in DMEM (Dulbecco's modified Eagle's Medium, Lonza, 12-604F, USA), 3T3- L1 adipocyte, purchased from ATCC) were cultured. The medium was exchanged every other day, and cultured in a 37 ° C 5% CO ₂ incubator until 80% fusion. Then, 10% fetal bovine serum (Gibco co. USA), 0.5 mM 3-isobutyl-1-methyxanthine, Sigma co. USA, 1 μM dexamethasone, Sigma USA), and 167 nM insulin (Sigma co. USA) for 48 hours. The medium was then replaced with DMEM medium containing 10% fetal bovine serum and 167 nM insulin, Time was cultured. Finally, differentiated adipocytes were obtained by further culturing in a medium containing only 10% fetal bovine serum for 48 hours.

2. Drug treatment of differentiated adipocytes

After the complete differentiation, the culture medium was separated from the adipocytes and washed with PBS. Then, 2% free fatty acid bovine serum albumin (Sigma Co., USA) was added to low glucose glucose DMEM (With 1000 mg / L D -glucose, without L-glutamine, without phenol-red, LM001-04, Welgene, Korea) and cultured in a 10% CO ₂ incubator for 24 hours. (70%, PFI co. Japan) for positive control, normal green tea hot water extract (BTC, Korea) for negative control, 16-hydroxy-octadeca-9,17-diene -12,14-dienyl ester acetic acid were each treated at 10 占 퐂 / ml and cultured in a 37 占 폚 5% CO ₂ incubator.

3. Measurement of fat resolution after drug treatment on fully differentiated adipocytes

The culture medium of the cells cultured in the above step 2 was collected and each 50 μl each was dispensed into a microplate. The reaction mixture A of the free fatty acid measurement kit (Roche, Cat #. 1-383-175, Germany) 50 ㎕ of the same amount as the sample was dispensed into each cell and reacted at 25 캜 for 10 minutes. 5 ㎕ of N-ethyl-maleinimide solution was dispensed into each cell and initial absorbance was measured at 546 nm Respectively. Reaction mixture B was dispensed into each well in an amount of 5 쨉 l each well. Then, after reacting at 25 DEG C for 15 minutes, the final absorbance was measured. The final value was determined by subtracting the initial value from the absorbance of the blank, and the limit value was determined as the final free acid concentration in the difference value of each sample. The results are shown in Fig.

1 shows that 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid used in the present invention exhibits excellent fat resolution, It can be seen that it shows higher lipolytic ability compared to tea catechin.

[ Test Example  3] DIO ( Diet - Induced Obesity ) Serum chemistry in the model

1. Sample Preparation

The tea catechin (70%, Pharmafood Inc. Japan) 200 mpk, used as a control in animal experiments, was dissolved in HPLC grade H ₂ O (Sigma co. USA) before oral daily administration and the 16-hydroxy- Octadeca-9,17-diene-12,14-dienyl ester acetic acid was prepared by dissolving in HPLC grade H ₂ O prior to oral administration at a concentration of 20 mg / kg.

2. Experimental group  Establishment, weight loss and lipidation effect verification

For this experiment, 10 mice per 7 weeks old C57BL / 6J male rats were prepared. After 1 week of adaptation period, the mice were separated from each other and separated by 12 hours interval (6 ~ 18h) It was managed according to the night cycle. 2) high-fat diet group (control group), 3) high fat diet group, and 200-ck intake group of tea catechin (tea catechin), 4) high fat diet group and 16- Di-12,14-dienyl ester acetic acid (20mpk), which were divided into 4 groups, and were orally administered at a fixed time (10:00 am) for 8 weeks once a day. The control group, Were given the same amount of water.

Body weight was measured once a week (11 am). The final body weight of the experimental group and the control group was measured 8 weeks after the start of administration and the results are shown in FIG.

2, when 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid used in the present invention was administered, And the weight reduction effect is better than that of tea catechin, which is known to be effective for weight reduction.

In addition, the weight of epididymal fat of each population was measured after autopsy at 8th week. As a result, the control group was 2.89. + -. 0.58 g, but the epinephrine weight of the group ingested with 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid was found to be 1.65 ± 0.23 g on average. This result was calculated by converting the epididymis weight to the average body weight. The calculation results are shown in Table 1 below.

Reduction of epididymal fat weight by administration of 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid Experimental group Epididymis  Weight (g) Normal diet 1.23 + - 0.32 Highland method 2.89 ± 0.58 High fat / tea catechin 2.13 + - 0.46 High fat / 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid 1.65 ± 0.23

Table 1 shows that when 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid used in the present invention was administered, similar to the case of the normal diet , The weight loss of epididymal fat was reduced, and the weight reduction effect of epididymal fat was better than that of tea catechin.

3. Experimental group  And control serum

The long-term toxicity test was conducted by administering tea catechin and 16-hydroxy-octadeca-9,17-dien-12,14-dienyl ester acetic acid for 8 weeks to C57BL / 6J mice used for the tests such as prevention and treatment of obesity Respectively.

In order to investigate the effects on the organs (tissues) of the animals, experimental groups treated with tea catechin and 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid by concentration, After 8 weeks from the control animals, the blood was collected and the blood concentrations of GPT (glutamate-pyruvate transferase) and BUN (Blood Urea Nitrogen) were measured using Select E (Vital Scientific NV, Netherland) . The measurement results are shown in Table 2 below.

Serum GPT and BUN Concentration Experimental group GPT BUN Normal diet 62.13 + - 3.38 19.68 ± 1.05 Highland method 89.31 + - 7.21 22.48 ± 1.21 High fat / tea catechin 69.21 + - 6.78 20.56 ± 0.91 High fat / 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid 63.31 + - 2.58 19.45 ± 0.72

In Table 2, when 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid used in the present invention was administered, , And GPT and BUN concentrations were lower than those of tea catechins. The results are shown in Fig.

In addition, GPT is an index for confirming hepatotoxicity, and BUN is an index for confirming renal toxicity. BUN associated with hepatotoxicity-related GPT and renal toxicity did not show any significant difference compared to the control group. In addition, liver and kidney were extracted from each animal, and histological observation was performed with an optical microscope through a typical tissue section production process. No abnormal abnormalities were observed. Thus, the 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid according to the present invention will be considered to be without particular toxicity.

Glucose (glucose) indicators are related to blood sugar, and high levels may indicate diabetes. TG (triglyceride) is also a blood fat component that causes atherosclerosis with cholesterol. In addition, CHOL (cholesterol) is an index to help diagnose obesity, liver disease and diabetes. The measurement results of these values are shown in Table 3 below.

Changes in Blood Glucose and Lipid Concentration Following 16-Hydroxy-octadeca-9,17-Diene-12,14-Dinyl Ester Acetic Acid Administration Experimental group GLUC TG CHOL Normal diet 112.41 + - 5.56 78.24 + - 6.42 103.64 ± 6.33 Highland method 168.32 + - 4.18 121.24 ± 10.21 195.12 ± 21.68 High fat / tea catechin 144.54 + - 5.68 105.46 ± 8.11 156.51 ± 18.12 High fat / 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid 125.17 + - 4.32 98.12 ± 6.19 132.18 ± 16.22

In Table 3, both GLUC and CHOL were found to show lower values when treated with 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid compared to the control. Therefore, it can be seen that the composition according to the present invention is effective for the treatment and prevention of diabetes and obesity.

TG (triglyceride) is also a blood fat component that causes atherosclerosis with cholesterol. In Table 3, the TG levels were significantly lower in the experimental group to which 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid was administered compared to the control group.

Therefore, the composition according to the present invention has an effect of lowering both CHOL and TG levels, and thus it has been found to be effective in the treatment and prevention of hyperlipemia, hypertension, arteriosclerosis, angina pectoris and myocardial infarction.

[ Test Example  4] Male SD Rat Adipocyte  Evaluation of Triglyceride Decomposition Promotion Efficiency

Experiments were carried out using isolated epididymal adipocytes to evaluate the effect of promoting triglyceride degradation in adipocytes in male SD rats.

First, epididymal adipose tissue was isolated by the following method. The epididymal adipose tissue of SD male rats was cut off with scissors and 0.1% collagenase (in DMEM without phenol red) was added. Then, the cells were incubated at 37 ° C for 2 hours and then filtered to obtain adipocytes.

Colorless DMEM (Dulbecco-modified eagles medium) containing 0.5% bovine serum albumin (BAS) without fatty acids was added to adipocytes and used for the experiments. The amount of glycerol was quantified by the color reaction using a GPO-trinder kit purchased from Sigma (St. Louis, Mo., USA) and absorbance was measured at 540 nm using an ELISA reader.

As a control, a test substance or a test substance was used, and 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid was used as a test substance. , Caffeine was used, and these substances were added in an amount of 50 μg / ml each. As the fat is hydrolyzed, it is decomposed into fatty acid and glycerol. Therefore, the degree of fat decomposition was determined by measuring the concentration of glycerol liberated from the adipocyte into the culture medium. The result was converted to other values when the control group was set to 1 Respectively. The results are shown in Fig.

As shown in FIG. 3, when treated with 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid, the fatty acid decomposing effect was at least 2 times higher and 3 times higher than that of the control group .

[ Test Example  5] Effect on Lipid Metabolism of Animal

To investigate the effect of the composition of the present invention on lipid metabolism in obese animals induced by high fat diet, male SD white rats were selected as a model.

To investigate how 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid affects obesity induced by high fat diet, 6-week old rats were adapted for one week, Ten animals were randomly assigned. The experimental group was divided into two groups: normal fat diet group, high fat diet group, high fat diet group + 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid 1%

Experimental diets were fed for 8 weeks. Experimental diets were prepared as shown in Table 4 below. At this time, the experimental diets were prepared on the basis of AIN-93G refined feed and high fat diet (18% in diet) in which the fat was adjusted to 36% of the total calories, so that fat was 17% (7% in the diet).

Feed ratio of each experimental group Experimental group Jeongsangsik ¹⁾ Highland method When the high-order system is a combination of + 16-hydroxy-octadeca-9,17-dien-12,14-
Dienyl ester acetic acid Corn starch 529.486 419.486 409.486 Casein 200.0 200.0 200.0 Sucrose 100.0 100.0 100.0 Soybean oil 70.0 180.0 180.0 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester Acetic acid - - 10 Fiber 50.0 50.0 50.0 Mineral mixture ^{2 )} 35.0 35.0 35.0 Vitamin mixture ^{3 )} 10.0 10.0 10.0 L-cystine 3.0 3.0 3.0 Choline bitartrate 2.5 2.5 2.5 Tert-butyl hydrogen peroxide 0.014 0.014 0.014 Energy Total (Kcal) 3498 4502 4496

1) Normal diet: AIN-93G diet

2) Mineral mixture: AIN-93G mineral mixture (g / kg mix)

3) Vitamin mixture: AIN-93G vitamin mixture (g / kg mix)

Dietary intake and body weight were measured once a week in the empirical formula during the pay period, and the empirical formula was finally measured at the end of the pay period. The results of body weight changes according to the experimental diet are shown in Tables 5 and 6 below.

Weight difference and food intake in each group Experimental group Dietary intake Weight before start of experiment (g) Food intake (g / day) One (C) 178.6 ± 10.1 27.2 ± 3.5 2 Highlander (HF) 176.9 ± 14.2 26.5 ± 5.4 3 High-level method (HF) +
16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester Acetic acid 1.0% 181.5 ± 10.3 25.4 ± 3.6

As shown in Table 5, there was no difference in body weight between the experimental groups before the start of the experiment and there was no significant difference in the dietary intake among the groups. However, as shown in Table 6 below, the change in body weight after feeding was 408.2 ± 20.1 in the case of the normal diet group and 557.2 ± 17.5 in the control group, the weight group was higher than that of the normal diet group. The body weight of 1.0% of the 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid dihydrate group was 438.4 ± 15.7 to 486.3 ± 19.2g and the weight of the 16-hydroxy-octadeca- Diene-12,14-dienyl ester acetic acid diet group showed significantly lower body weight gain (P <0.05).

Weight change after each experiment Experimental group Dietary intake Weight after experiment (g) Weight change (g) One It's normal. 408.2 ± 20.1 229.6 ± 15.6 2 It's a highland system. 557.2 ± 17.5 380.3 ± 46.3 3 High-grade system / 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester Acetic acid 467.6 + 14.3 286.1 ± 31.5

The results in Table 6 show that 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid is effective in preventing weight gain and can help prevent and improve obesity have.

[ Test Example  6] Epididymis  Measurement of weight

The experimental groups 1 to 12 of Test Example 5 were sacrificed after 8 weeks of dieting and the epididymal fat was extracted. The extracted epididymal fat was washed with physiological saline, lightly removed from the filter paper and weighed. The results are shown in Table 7 below.

Epididymal fat weight for each group Experimental group County Epididymal fat weight (g) One It's normal. 18.9 ± 2.6 2 It's a highland system. 47.8 ± 6.9 3 High-grade system / 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester Acetic acid 35.2 ± 7.1

The results of Table 7 show that 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid is superior in suppressing the increase in body fat mass.

[ Test Example  7] CPT -1

The experimental groups 1 to 3 of Test Example 5 were sacrificed after 8 weeks of dieting and the liver was extracted. The extracted liver tissues were homogenized and RNA was extracted using TRIZOL (Life Technologies, grand Island, NYU, USA), which was a mixed solution of phenol and guanidine isothiocyanate. The degree of expression of CPT-1 mRNA from the total RNA thus obtained was measured by Q-PCR, and quantified and shown in FIG.

As can be seen in Fig. 4, CPT-1 expression was increased in the dietary group fed with 16-hydroxy-octadeca-9,17-diene-12,14-dienyl ester acetic acid compared to the high fat diet group have.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. something to do. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (10)

Octadeca-9,17-diene-12,14-diynyl ester represented by the following general formula (1): ???????? 16-hydroxy-octadeca- As an active ingredient for preventing or ameliorating the metabolic syndrome.
[Chemical Formula 1]

The pharmaceutical composition according to claim 1, wherein the metabolic syndrome is selected from the group consisting of diabetes, cardiovascular disease, obesity, and hyperlipidemia. The pharmaceutical composition for preventing or improving metabolic syndrome according to claim 1, wherein the active ingredient degrades triglycerides. The pharmaceutical composition for preventing or improving metabolic syndrome according to any one of claims 1 to 3, wherein the active ingredient is contained in an amount of 0.001 to 50% by weight based on the total weight of the composition. 4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the pharmaceutical composition comprises at least one pharmaceutically acceptable carrier or excipient. Octadeca-9,17-diene-12,14-diynyl ester represented by the following general formula (1): ???????? 16-hydroxy-octadeca- As an active ingredient for preventing or ameliorating the metabolic syndrome.
[Chemical Formula 1]

[Claim 7] The composition of claim 6, wherein the metabolic syndrome is selected from the group consisting of diabetes, cardiovascular disease, obesity, and hyperlipidemia. The health functional food composition according to claim 6, wherein the active ingredient degrades triglycerides. 9. The health functional food composition according to any one of claims 6 to 8, wherein the active ingredient is contained in an amount of 0.001 to 50% by weight based on the total weight of the composition. 9. A health functional food for preventing or improving metabolic syndrome according to any one of claims 6 to 8, characterized in that the health food composition further comprises a pharmaceutically acceptable excipient in the form of a food or an edible drink Composition.

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