WO2015030293A1

WO2015030293A1 - Composition containing composite extract of grape and schisandra chinensis for preventing or treating metabolic syndrome-related diseases

Info

Publication number: WO2015030293A1
Application number: PCT/KR2013/009339
Authority: WO
Inventors: 김혜진; 심재석; 박석준; 신동주; 최명숙; 조수정
Original assignee: 씨제이제일제당 (주)
Priority date: 2013-08-30
Filing date: 2013-10-18
Publication date: 2015-03-05
Also published as: WO2015030336A1; KR20150027676A; KR101610466B1

Abstract

The present invention relates to a composition containing, as an active ingredient, a composite extract of grape and Schisandra chinensis, for preventing or treating metabolic syndrome-related diseases, a method for preventing or treating metabolic syndrome-related diseases using the composition, a food composition, a feed additive or a composition for feed, and a medicinal composition containing a composite extract of grape and Schisandra chinensis for preventing or alleviating metabolic syndrome-related diseases. According to the present invention, the composite extract of grape and Schisandra chinensis has been confirmed to reduce the weight of body fat, and specifically, the weight of white adipose tissue thereby reducing the amount of overall weight gain, and to control various biomarkers and adipokines related to metabolic syndrome, and thus to be effective in preventing and treating metabolic syndrome including hyperlipemia, diabetes, and liver diseases. Therefore, the present invention has the advantage of providing the composition containing, as an active ingredient, the composite extract of grape and Schisandra chinensis, for preventing or treating metabolic syndrome-related diseases. The present invention also can be applied to the food composition, livestock feed, or to a feed additive for preventing or alleviating metabolic syndrome-related diseases.

Description

Composition for the prevention or treatment of metabolic syndrome-related diseases, including grape and Schisandra chinensis extract

The present invention relates to a composition for the prevention or treatment of metabolic syndrome-related diseases comprising grape and Schisandra chinensis extract as an active ingredient, a method for preventing or treating metabolic syndrome-related diseases using the composition, metabolic syndrome comprising a grape and Schisandra chinensis extract It relates to a food composition, feed additive or feed composition and quasi-drug composition for the prevention or improvement of diseases.

Recently, the development of metabolic syndrome-related diseases including various diseases such as obesity, hyperlipidemia, hypertension, arteriosclerosis, hyperinsulinemia, diabetes, or liver disease are rapidly increasing according to economic development and changes in eating habits. Although these diseases occur individually, they are usually closely related to each other and often accompanied by various symptoms.

Obesity is known to cause chronic diseases such as fatty liver, high blood pressure, diabetes, and cardiovascular disease. According to the 2007 National Health and Nutrition Survey of the Ministry of Health, Welfare and Family Affairs, 31.7% of Korean adults are obese. In addition, 1.7 billion people, or 25% of the world's population, are currently overweight (BMI> 25), and more than 300 million people in the Western region, including 120 million in major countries such as the United States, Europe and Japan, are obese (BMI). 30). In China, 70 million people are known to be obese. In the world, 1 in 5 children are obese and are rapidly increasing, so childhood obesity is a serious social problem. Generic drugs that are sold at home and abroad are orlistat, which is approved by the US FDA. Xenical, which inhibits lipase action, has gastrointestinal side effects such as fatty stool, gas production, and decreased absorption of fat-soluble vitamins.

Hyperlipidemia leads to increased blood lipids such as cholesterol in the blood, which leads to poor blood flow, and the attachment of lipid components to arterial walls causes chronic inflammatory reactions. The blood clots generated from this block the coronary artery and the cerebral blood vessels, causing myocardial infarction, stroke or cerebral infarction. Currently, antilipidemic drugs are used in the statin class of drugs that inhibit HMG-CoA reductase, which plays an important role in the synthesis of cholesterol in the liver. It is known to have side effects such as muscle toxicity.

Hypertension is a condition in which the arterial blood pressure is chronically high, and systolic blood pressure is 140 mmHg or more or diastolic blood pressure is 90 mmHg or more in adults over 18 years old, and may be caused by obesity. At present, anti-hypertensive drugs have been developed, such as renin inhibitor drugs, angiotensin converting enzyme activity inhibitory drugs, and drugs that inhibit binding between angiotensin and angiotensin receptors, but there is still a need to develop more effective therapeutic agents.

Atherosclerosis is a condition in which fatty substances (plaque) containing cholesterol, phospholipids, and calcium accumulate in the vascular lining, which causes the arteries to become hard and lose elasticity and narrow, resulting in impaired blood supply or high pressure, resulting in arterial rupture and detachment. . Currently, various statins, such as HMG-CoA reductase inhibitors, have been developed as arteriosclerosis agents, but there is still a need for development of more effective therapeutic agents.

Hyperinsulinemia is a condition with high insulin levels in the blood and is associated with obesity or diabetes, such as promoting sympathetic hyperactivity or the absorption of sodium in the kidneys, and has fewer side effects and does not cause weight gain. There is an urgent need for the development of therapeutic agents that can lower insulin levels.

Diabetes is a type of disease in which carbohydrate metabolism is caused by lack of insulin or lack of insulin sensitivity. Type I is insulin-dependent diabetes mellitus (IDDM), formerly known as juvenile diabetes, and requires insulin injections. This is because insulin is not secreted from the pancreas, so insulin must be supplied by injection. Type II is a type of non-insulin-dependent diabetes mellitus (NIDDM) called adult diabetes, which can be controlled by diet. It is caused by poor insulin secretion of the pancreas or tissue rejection of insulin, which is exacerbated by subtle changes in beta cells secreting insulin. The two types of diabetes were previously classified as juvenile diabetes and adult diabetes, but both can occur at any age. However, insulin-independent diabetes is much more common, accounting for 90% of all diabetics. Insulin-dependent diabetes mellitus, namely type 1 (type I) diabetes, is currently the most common method of insulin injection. Meanwhile, PPAR-γ activators, GLP-1 derivatives, DPP-IV inhibitors, PTP1B inhibitors, and the like have been developed as substances for treating insulin-independent diabetes, that is, type 2 (type II) diabetes, as the main antidiabetic agents. Drugs have side effects due to their mechanisms. For example, the symptoms of weight gain along with toxicity to the liver, kidneys, muscles and heart are typical side effects. Therefore, there is an urgent need for the development of a diabetes treatment agent capable of effectively treating or preventing diabetes while at the same time having fewer side effects and causing weight gain.

Liver is the organ that plays a central role in nutrient metabolism. Normal human liver weighs about 1,500 g and abnormal liver function causes problems in nutrient metabolism in the body, making glucose into glycogen or protein in albumin. Abnormalities in liver function, such as switching to or dissolving unnecessary ones and delivering them to the bile. In case of mental rest, hepatic cells can be restored in the case of minor liver damage, but liver disease is aggravated because busy modern society cannot afford to rest. In general, hepatitis, which causes inflammation of the liver, accounts for most of liver diseases, and according to aspects, it can be divided into acute hepatitis, chronic hepatitis, and viral hepatitis, alcoholic hepatitis, and drug hepatitis depending on the cause. Liver diseases caused by these abnormalities include fatty liver, hepatitis, cirrhosis, liver cancer. Healing liver disease in combination with exercise, alcoholism, diet, and drug treatment, but fundamentally difficult to completely heal the development of effective and improved liver disease treatment or protection is needed.

In addition, due to the recent improvement in the standard of living due to economic development, the hygienic environment is improved and the calorie intake is rapidly increased due to the improvement of diet, while the lack of exercise and the amount of calories consumed are low, resulting in excessive accumulation of nutrients in the body. The incidence of various adult diseases is increasing. Among these diseases, especially fatty liver is caused by the accumulation of fat in the liver due to excessive fat or alcohol intake, increased liver fat synthesis, reduced triglycerides and burning, etc. In general, fatty liver has a fat percentage of 5% or more. Is defined.

Most of the fat accumulated in fatty liver is triglyceride, and fatty liver can be divided into alcoholic fatty liver due to excessive drinking and non-alcoholic fatty liver due to obesity, diabetes, hyperlipidemia or drugs. Alcoholic fatty liver is caused by excessive intake of alcohol, which promotes fat synthesis in the liver and does not undergo normal energy metabolism. Some people think that fatty liver is simply the accumulation of fat in the liver, but considering that 50% of patients who have been diagnosed as alcoholic fatty liver and 30% of patients who are identified as nonalcoholic fatty liver develop liver cirrhosis, fatty liver is very serious. It should be considered one of the liver diseases. At present, there are few drugs that are useful for pharmacological treatment of fatty liver, and only exercise and diet are recommended, but in reality, the treatment efficiency of fatty liver by such a method is very low, and an effective therapeutic agent is required. It has been reported that some hypoglycemic agents, such as metformin, are effective in treating fatty liver, although fatty liver has been found to be associated with insulin resistance in cells observed in diabetes and obesity, but the drug has side effects such as liver toxicity or lactic acidosis. There is a problem that causes. In addition, alternative drugs, such as betaine, glucuronate, methionine, choline and lipotrophic agents, may be used as supplements, It is not fully proven. Therefore, the development of a safe fatty liver treatment that does not cause side effects with excellent effects is urgently needed.

In view of the problems with various metabolic diseases, the present inventors have no side effects on metabolic syndrome-related diseases including hyperlipidemia, diabetes mellitus, liver disease, and the like. In particular, it is possible to reduce the weight of white adipose tissue, thereby reducing the overall weight gain, and to control various metabolic syndrome-related biomarkers and adipocaine to prevent, ameliorate and treat diseases related to metabolic syndrome. The present invention has been completed by confirming that it can be represented.

An object of the present invention to provide a pharmaceutical composition for the prevention or treatment of metabolic syndrome-related diseases comprising grape and Schisandra chinensis extract as an active ingredient.

Another object of the present invention is to provide a method for treating metabolic syndrome-related diseases, comprising administering to the subject in need thereof a pharmaceutical composition for preventing or treating the metabolic syndrome-related diseases.

Another object of the present invention to provide a quasi-drug composition for the prevention or improvement of metabolic syndrome-related diseases comprising grape and Schizandra complex extract as an active ingredient.

Another object of the present invention to provide a feed additive or feed composition for the prevention or improvement of metabolic syndrome-related diseases, including grape and Schizandra complex extract as an active ingredient.

Another object of the present invention to provide a food composition for the prevention or improvement of metabolic syndrome-related diseases comprising grape and Schizandra complex extract as an active ingredient.

The present invention, grape and Schisandra chinensis extract can reduce the body fat weight, in particular, the weight of white adipose tissue, thereby reducing the overall weight gain, by controlling various metabolic syndrome related biomarkers and adipocaine hyperlipidemia, By confirming that diabetes and liver disease is effective in preventing and treating metabolic syndrome, such as, there is an effect that can provide a composition for the prevention or treatment of metabolic syndrome-related diseases comprising grape and Schizandra complex extract as an active ingredient. It may also be applied to food compositions, animal feed or feed additives for the prevention or improvement of metabolic syndrome-related diseases.

Figure 1 is a diagram showing the weight gain compared to the control group in the animal experiments fed grape extract (grape single group), Schizandra extract (Schisandra chinensis), or grape and Schizandra extract (grape Schizandra complex group).

Figure 2 is extracted from a single group of grapes, Schisandra chinensis, grape schisandra complex group, and the control group of white adipose tissue (epidermal fat, periphery fat, posterior cavity fat, mesenteric fat, subcutaneous fat, scapular fat) Figures comparing fat weights.

Figure 3 is a diagram comparing the size of the cells by measuring the image of the adipocytes in the grape single group, Schizandra single group, grape Schizandra complex group and the control group. It can be seen that the fat cells of the grape schizandra complex group are the smallest.

Figure 4 is a diagram measuring the expression level of adipocaine, adipose gene, and inflammatory gene by separating the plasma from the blood collected from the grape single group, grape Schizandra complex group and control group.

Figure 5 is a comparison of the expression of inflammatory genes and fat synthesis genes in the adipose tissue of grape single group, grape Schizandra complex group and control group.

Figure 6 is a comparison of the measurement of lipid composition, especially free fatty acid, triglyceride, and cholesterol concentrations in liver tissue of grape single group, grape Schizandra complex group and control group.

Figure 7 is a diagram comparing the liver tissue of the grape single group, grape Schizandra complex group and the control group.

Figure 8 is a comparison of the expression of lipid metabolism-related genes in liver tissue in the grape single group, grape Schizandra complex group and the control group.

9 is a diagram comparing the expression of inflammatory genes in liver tissue in the grape single group, grape Schizandra complex group and the control group.

10 is a total of six sites of white adipose tissue (didymicular fat) in an animal test fed HGO (high grape and omija extract) containing grape extract and LGO (low grape and omija extract) containing low ratio , Renal peritoneal fat, posterior cavity fat, mesenteric fat, subcutaneous fat, scapula fat) were extracted and compared with the control group.

11 is a diagram showing the results of comparing the total adipose tissue weight in the HGO treatment group, LGO treatment group and control group.

12 is a diagram comparing H & E staining of liver tissues of HGO treated group, LGO treated group and control group.

Figure 13 is a diagram showing the results of comparing the fatty acid synthesis-related genes and fatty acid oxidase activity of the liver operation in the HGO treatment group, LGO treatment group and the control group.

As one aspect for achieving the above object, the present invention provides a composition for the prevention or treatment of metabolic syndrome-related diseases comprising grape and Schizandra complex extract as an active ingredient.

The term "grape" in the present invention means a plant belonging to Vitis sp. ( Vitis sp. ), Including its fruit, which may include both grape fruit and vine, in particular the bark of grape fruit And stems of vines. The bark of the fruit is reddish brown and split long and long. It is largely divided into European species, American species, and hybrid species. In Korea, we plant American species and hybrid species that are resistant to cold and pests. Most of them are grown. The most cultivated varieties in Korea are campbell purple-black, medium in size and mature at the end of summer. It is known to have a lot of sugars, which are good for fatigue recovery, and are rich in vitamins, which are known to facilitate metabolism. Other minerals include calcium, phosphorus, iron, sodium and magnesium. It is known to act on blood and hematopoiesis, and it is known to have antiviral effect and anticancer component including resveratrol component. In the present invention, grapes can be purchased commercially, or can be used collected or grown in nature.

As used herein, the term “ Schisandra chinensis ” refers to a dark red fruit with a diameter of about 1 cm. It contains 1 to 2 seeds of red juice and reddish brown seeds. Types include North Schisandra chinensis, South Schisandra chinensis, and Black Schisandra chinensis. It is known that it can be used as a tonic because it contains ingredients such as cyxanthrin, gomisin, citric acid, malic acid, and citric acid, which strengthens the heart, lowers blood pressure, and boosts immunity. In the present invention, Schisandra chinensis can be purchased commercially, or may be used collected or grown in nature.

In the present invention, the term "extract" refers to the grape, Schisandra chinensis extract or a combination extract thereof. The grape and Schisandra chinensis extract may be prepared by grinding the pulverized powder of each component with about 5 to 30 times the dry weight, preferably about 10 to 20 times the volume of water, methanol, ethanol, etc. 1 (C1) to 4 (C4) It is possible to elute a polar solvent such as a lower alcohol of or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, and the extraction temperature is 20 to 100 ℃, preferably 60 to 100 ℃, extraction The period may be an extract extracted by using an extraction method such as hot water extraction, cold needle extraction, reflux cooling extraction or ultrasonic extraction for about 1 hour to 4 days, but the extract may exhibit a therapeutic effect of the metabolic syndrome-related diseases of the present invention. However, the present invention includes, but is not limited to, an extract, a diluent or concentrate of the extract, a dried product obtained by drying the extract, or all of these modifiers or purified products. The grape extract, Schisandra chinensis extract can be extracted from various organs of natural, hybrid, varieties, for example, roots, ground, stems, leaves, flowers, the trunk of the fruit, the bark of the fruit as well as plant tissue culture It is possible.

In the present invention, the grape extract may be obtained from one or more selected from the group consisting of a skin of grapes (aka juice gourd), grape seeds, and grape stems, and may be particularly obtained from a mixture of peel and stem. Thus, the grape extract may be obtained from a mixture of the skin and stem of the grapes in a 0.5 to 4: 1 weight ratio, in particular obtained from a mixture of the skin and stem of the grapes in a weight ratio of 2: 3 to 4: 1 It may be.

In one embodiment of the present invention was used dry grape pulverized product prepared by cutting the grape skin and stem of grape juice by-products and dried to within 10% moisture content. 200 g each of well-pulverized grapes (shell: stem = 80 g: 120 g) was added 4000 ml of an aqueous 80% ethanol solution, extracted at 80 ° C. for 2 hours, and concentrated under reduced pressure at 50 ° C. In addition, after purchasing and grinding Mungyeong dried Schizandra chinensis powder, 4000 ml of an aqueous 50% ethanol solution was added to 200 g of Schizandra chinensis, and extracted at 80 ° C for 2 hours, and then concentrated under reduced pressure at 50 ° C. The concentrate was lyophilized to finally obtain 60 g and 116 g of grape extract and Schisandra chinensis extract, respectively. Each extract was mixed and used in a set ratio to prepare the complex.

In the present invention, the grape and Schisandra chinensis extract may include grape extract and Schisandra chinensis extract in a weight ratio of 3 to 15: 1, and in particular, may comprise 4 to 12: 1 in weight ratio.

In one embodiment of the present invention, the grape extract and Schisandra chinensis extract were mixed at a weight ratio of 1: 1, 6: 1 or 10: 1, respectively, to determine the polyphenol ratio thereof. According to this, when the ratio of grapes was increased and the ratio of Schizandra was lowered compared to when mixed in a 1: 1 weight ratio, the total amount of polyphenols extracted, flavonoids and anthocyanin% by weight were mixed when mixed in a 6: 1 and 10: 1 weight ratio. It was confirmed that the increase of about 1.5 times (Table 7).

Accordingly, based on the content of the polyphenols, flavonoids and anthocyanins, the mixing ratio of the grape extract and the Schizandra chinensis extract is 6: 1 to 10: 1 by weight based on the criteria of 10% or more of polyphenols, 6% or more of flavonoids, and 1% or more of anthocyanins. Set to, verify the effect through animal experiments.

The composition of the present invention can reduce the body fat weight, in particular can reduce the weight of the white adipose tissue, thereby reducing the overall weight gain. It can also reduce the size of adipose tissue cells. In addition, it can reduce the expression of metabolic syndrome-related adipocaine and adipogenic genes, as well as reduce the expression of genes associated with inflammatory properties in adipose tissue. The adipocaine may be Leptin, the adipogenic gene may be PAI-1 or Resistin, and the gene associated with inflammatory may be NF-κB, TNFα, IL-6 or MCP-1, but is not limited thereto. In addition, it may have a characteristic of inhibiting lipid accumulation in liver tissue, specifically, may lower the concentration of free fatty acids, triglycerides and cholesterol in liver tissue. It is possible to reduce the expression levels of genes related to fatty acid influx or fatty acid synthesis and cholesterol regulatory genes and inflammatory genes in liver tissues that affect lipid accumulation in liver tissues, while increasing the expression levels of genes related to fatty acid oxidation. have. The gene involved in fatty acid influx or fatty acid synthesis may be CD36, FAS, ACC1, SCD1, ME or LPL, the cholesterol regulatory gene may be HMGR or ACAT, and the inflammatory gene may be as described above. Also, the fatty acid oxidation related gene may be a β-oxidaion related gene.

In particular, the composition of the present invention may be a composition comprising any one or more of the following features a) to g).

a) inhibiting adipocaine expression or secretion;

b) inhibiting fat biosynthetic gene expression;

c) inhibiting adipocyte-forming gene expression;

d) inhibiting inflammatory gene expression;

e) inhibition of gene expression associated with fatty acid influx;

f) inhibition of fatty acid biosynthetic gene expression; And

g) inhibition of cholesterol regulatory gene expression.

As used herein, the term "adipokine" generally refers to substances secreted from adipocytes, which are derived from cytokines which refer to substances secreted from cells and affect the function of oneself or other cells. It is a word that means cytokine secreted by fat cells, it is also used as adipocytokine. Representative adipocaines include leptin, tumor necrosis factor (TNF) -α, interleukin-6, lasminogen activator inhibitor-1, adiponectin and resistin. Recently, new adipocaines such as visfatin and retinol binding protein 4 (RBP4) It is known all the time. A common feature of adipocaine is that their secretion responds to changes in long-term homeostasis—weight changes, insulin sensitivity, rather than abrupt environmental changes. If it is possible to control the concentration of adipocaine, it is possible to improve, prevent or treat various metabolic syndrome-related diseases.

Through various actions in the adipose tissue and liver tissue as described above, the composition of the present invention can prevent or treat diseases related to metabolic syndrome such as obesity, hyperlipidemia, hypertension, arteriosclerosis, hyperinsulinemia, diabetes, or liver disease. .

The composition of the present invention can prevent or treat metabolic syndrome accompanied by the above symptoms by the effect of reducing adipose tissue, inhibiting lipid accumulation of liver tissue, promoting fatty acid oxidation and the like.

The composition of the present invention can treat or prevent liver disease through reduced expression of inflammatory genes in adipose tissue or liver tissue.

As used herein, the term "metabolic syndrome related disease" refers to various diseases that occur due to metabolic problems, and the disease capable of treating or preventing the grape schizandra complex extract of the present invention as an active ingredient includes, without limitation, For example, it may be one or more diseases selected from the group consisting of obesity, hyperlipidemia, hypertension, arteriosclerosis, hyperinsulinemia, diabetes and liver disease.

In the present invention, the term "hyperlipidemia" refers to a disease caused by a large amount of fat in the blood due to poor metabolism of triglycerides and cholesterol. Specifically, high cholesterol and hypertriglyceridemia are included as an increase in lipid components such as triglycerides, LDL cholesterol, phospholipids and free fatty acids in the blood.

In the present invention, the term "hypertension" is a state in which the arterial blood pressure is chronically high, and refers to a case where the systolic blood pressure is 140 mmHg or more or the diastolic blood pressure is 90 mmHg or more in an adult 18 years or older, and may be caused by obesity or the like.

In the present invention, the term "arteriosclerosis" means that arteriosclerosis is a fatty substance (plaque) containing cholesterol, phospholipids, calcium, etc. accumulate in the vascular lining, so that the arteries become hard and lose elasticity, which narrows the blood supply or increases the pressure. It refers to a state where rupture or peeling occurs.

In the present invention, the term "hyperinsulinemia" is a condition associated with obesity or diabetes, such as a state of high insulin level in blood, promoting hypersympathetic activity, sodium absorption in the kidney, and the like.

In the present invention, the term "diabetes" refers to a disease that occurs when insulin secretion is insufficient or when insulin does not sufficiently function and function, and when this disease occurs, glucose in the liver or blood due to excessive decomposition of glycogen, protein and fat An abnormal increase in concentration causes diabetes and ketoneuria, resulting in pathological conditions such as circulatory disorders and kidney disorders along with blood concentration due to electrolyte loss due to abnormality of water and electrolyte metabolism. Insulin is secreted from the beta cells of the island of Langerhans in the pancreas, secreted when blood glucose concentration increases, and when decreased, secretion is inhibited to regulate proper activity of energy sources. The disease is divided into insulin dependent diabetes mellitus (type I) and insulin independent diabetes mellitus (type II). Diagnosis of diabetes is generally possible through measurement of blood glucose levels, which differ according to criteria. In humans, diabetes is usually diagnosed when glucose in the blood is at least 200 mg / dl and fasting at 140 mg / dl. Therefore, lowering the glucose concentration in the blood or in the liver can treat or prevent diabetes.

In the embodiment of the present invention, when a diet containing a composition containing grape and Schisandra chinensis extract in an animal model inducing hyperlipidemia with a high-fat diet, the body fat weight reduction, in particular, the weight of white adipose tissue is reduced As a result, the weight was confirmed to decrease (FIGS. 1 and 2). Plasma adipocaine and gene expression were also measured to confirm that the complex extract of the present invention inhibited adipocaine expression or secretion, adipogenic gene expression, and also inhibited the expression of inflammatory genes in adipose tissue (FIG. 4 and FIG. 5).

In an embodiment of the present invention, metabolic syndrome model animal (db / db-) dietary supplement with the grape and Schisandra chinensis extract, or containing a high percentage of HGO (high grape and omija extract) containing a high percentage of grape extract LGO (low grape and omija extract) was fed diet. As a result, it was confirmed that the complex composition caused a change in lipid concentration in liver tissue (FIGS. 6 and 7), and in this regard, expression of fatty acid influx and synthesis related genes was suppressed (FIG. 8), and expression of cholesterol regulatory genes. In addition, it was confirmed that the gene involved in fatty acid oxidation is overexpressed (FIG. 13). In addition, it was confirmed that also inhibit the expression of inflammatory genes in liver tissue (Fig. 9). In particular, in FIGS. 11 to 13, when the LGO composition containing the grape extract at a low rate was administered, the degree of decrease in total adipose tissue weight than HGO was significantly increased, but fatty acid oxidation efficiency was slightly increased. there was.

In the embodiment of the present invention, for the metabolic syndrome including various factors such as hyperlipidemia and diabetes, metabolic syndrome-related symptoms in metabolic syndrome model animals as well as inhibiting hyperlipidemia induced by high fat diet Effective in the treatment, it was confirmed that the grape and Schisandra chinensis extract have a useful activity in the treatment and prevention of metabolic syndrome encompassing these various symptoms.

As used herein, the term "liver disease" includes without limitation liver diseases that can be treated by the composition of the present invention, for example, non-alcoholic fatty liver, alcoholic fatty liver, non-viral chronic hepatitis, cirrhosis, chronic liver disease, Liver cancer and the like.

As used herein, the term "non-viral" refers to an illness caused by alcoholic, non-alcoholic (obesity, diabetes, hyperlipidemia) or other (toxic, pollution, drug, neurological, overworked) causes.

As used herein, the term “fatty liver” refers to a phenomenon in which triglycerides appear abnormally deposited in liver cells, unlike normal cases. About 5% of normal liver is composed of fatty tissue, and triglycerides, fatty acids, phospholipids, cholesterol, and cholesterol esters are the main components of fat, but once fatty liver occurs, most of the components are replaced by triglycerides. If more than 5% of the liver weight is diagnosed as fatty liver. Fatty liver is caused by a fat metabolism disorder in liver cells or a defect in the process of carrying excess fat, and is mainly caused by a fat metabolism disorder in the liver. Most of the fat accumulated in the fatty liver is triglyceride, and fatty liver can be divided into non-alcoholic fatty liver due to obesity, diabetes, hyperlipidemia, drugs, and alcoholic fatty liver due to excessive drinking. The non-alcoholic fatty liver alcohol intake history refers to a case with fatty liver without history, and is known to be associated with metabolic diseases such as obesity, diabetes, hyperlipidemia. These nonalcoholic fatty livers include not only fats accumulated in the liver, but also non-alcoholic steatohepatitis or terminal fibrotic liver disease. Alcoholic fatty liver is due to the consumption of alcohol to promote the synthesis of fat in the liver and occurs due to the lack of normal energy metabolism. Alcohol is not stored in the body and is completely eliminated by oxidation in the liver. Specifically, alcohol in the liver is largely alcohol dehydrogenase (ADH) pathway, microsomal ethanol oxidizing system (MEOS). It is metabolized and converted into acetaldehyde by three pathways, a) and a catalase pathway, which are in turn metabolized to acetitis by dehydrogenase (ALLDH). At this time, acetaldehyde may be toxic and damage liver cells. In addition, in the microsomal alcohol oxidative pathway, superoxide (O) in the process of alcohol metabolism is activated by cytochrome P450-2E1 (CYP2E1; cytochrome P450 2E1). ₂ ), reactive oxygen species (ROS) such as hydrogen peroxide (H ₂ O ₂ ) and peroxynitrite are formed to cause oxidative stress and cause liver damage. In addition, as a result of the metabolism of alcohol, fatty acids are made up to accumulate fat in the liver. Fatty liver accumulated in the liver due to the above causes is called alcoholic fatty liver.

Fatty liver is mostly associated with obesity, but it can also occur in people who are dry or normal. This may be supported by reports that 40% (32/81) of patients with fatty liver had a normal body mass index (Nucl. Med. Mol. Imaging., 40, 243-248 (2006)). In particular, triglycerides were reported to be a major factor in non-obese groups (J. Clin. Gastroenterol., 40, 745 ~ 752 (2006)). Is statistically significant, indicating that there is a high association between fatty liver and triglyceride in non-obesity cases.

As used herein, the term "chronic liver disease" includes chronic hepatitis, cirrhosis, and liver cancer, and cirrhosis, also called cirrhosis, refers to all forms of liver disease characterized by loss of a significant amount of liver cells, proliferation of fibrous tissue, and regenerative nodules. Say. The main causes of cirrhosis are hepatitis virus and alcohol, respectively, treated with antiviral therapy or alcohol / nutrition therapy. Complications can lead to death, including ascites (bleeding in the belly), varicose veins bleeding, and hepatic coma.

In the present invention, the term "liver cancer" refers to a disease resulting from patients with chronic liver disease caused by cirrhosis transducer, alcohol and the like. If you have a typical liver mass or if your blood test shows an increase in alpha-fetoprotein (AFP), you can diagnose it as a liver cancer.

The cause of all these liver diseases may vary from patient to patient, but if the disease becomes chronic, the disease progresses gradually to hepatitis, cirrhosis, liver cancer. Thus, the composition comprising the extract of grape and Schisandra chinensis extract as a result of the present invention is determined in the liver. It suggests that the expression of inflammation-related genes can be suppressed to treat or prevent liver disease.

Specifically, it was confirmed in the embodiment of the present invention that the expression of inflammatory genes in liver tissues was significantly lowered in the grape and Schisandra chinensis extracts in the feeding group compared to the grape extract single group or the control group in the animal experiment (FIG. 9). Accordingly, it was confirmed that the complex extract of the present invention may have a therapeutic effect on liver disease related to inflammation.

As used herein, the term "prevention" refers to any action that inhibits or delays the development of metabolic syndrome related diseases such as obesity, hyperlipidemia, hypertension, arteriosclerosis, hyperinsulinemia, diabetes, liver disease, etc. by administration of the composition according to the present invention. Say. As used herein, the term "treatment" refers to any action by which administration of a composition according to the invention improves or advantageously alters the symptoms of the diseases.

In a preferred embodiment of the invention, the composition of the invention is a pharmaceutical composition. When the composition of the invention is a pharmaceutical composition, the composition may comprise a pharmaceutically acceptable carrier.

The composition comprising a pharmaceutically acceptable carrier may be in a variety of oral or parenteral formulations. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin. In addition to simple excipients, lubricants such as magnesium stearate, talc and the like are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.

The pharmaceutical composition is any one selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, liquid solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories. It can have one formulation.

The composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level refers to the type and severity of the subject, the severity, age, sex and activity of the drug. , Drug sensitivity, time of administration, route of administration and rate of release, duration of treatment, factors including concurrently used drugs, and other factors well known in the medical arts.

A typical daily dosage of a composition comprising a grape and Schisandra chinensis extract according to the present invention as an active ingredient may range from 10 to 4,000 mg / day, preferably 200 to 2500 mg / day, based on an adult weight of 60 kg. It can be administered once or divided into several times.

In one embodiment of the invention, the effect is verified at a dose of 400 to 2000 mg / day based on 60 kg body weight adult.

The prophylactic or therapeutic agent for metabolic syndrome-related diseases such as obesity, hyperlipidemia, hypertension, arteriosclerosis, hyperinsulinemia, diabetes mellitus, liver disease, etc. may be administered daily or intermittently, and the number of administrations per day is one or two. It is possible to divide and administer 3 times. The frequency of administration in the case where the two active ingredients are single drugs may be the same or different times. In addition, the composition of the present invention can be used alone or in combination with other drug treatments for the prevention or treatment of liver disease diseases. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, and can be easily determined by those skilled in the art.

As another aspect, the present invention provides a method of treating metabolic syndrome-related diseases comprising administering a combination extract of grape and Schizandra chinensis to a subject in need thereof.

As used herein, the term "individual" means all animals including humans who have already developed or may develop metabolic syndrome-related diseases, and by administering to the individual a composition comprising grape and Schizandra chinensis extract as an active ingredient, It can be effectively prevented and treated. The subject means an entire mammal including a dog, cow, horse, rabbit, mouse, rat, chicken or human, but the mammal of the present invention is not limited to the above examples.

The optimal amount and dosage interval of the individual doses of the composition of the present invention will be determined by the nature and extent of the disease being treated, the dosage form, the route and site, and the age and health of the particular patient being treated and ultimately used by the physician. It will be appreciated by those skilled in the art that the appropriate dosage will be determined. Such dosing can be repeated as often as appropriate. If side effects occur, the dosage and frequency can be altered or reduced in accordance with normal clinical practice.

The route of administration of the composition may be administered via any general route as long as it can reach the desired tissue. The composition of the present invention may be administered as desired, but is not limited to intraperitoneal administration, intravenous administration, subcutaneous administration, intradermal administration, oral administration. The composition may also be administered by any device in which the active agent may migrate to the target cell.

As a preferred embodiment of the present invention, the composition of the present invention is a quasi-drug composition.

The grape and Schisandra chinensis extract is as described above. More specifically, the composition of the present invention can be added to the quasi-drug composition for the purpose of preventing or improving metabolic syndrome-related diseases.

As used herein, the term " improvement " refers to an effect of alleviating the symptoms of metabolic syndrome-related diseases such as hyperlipidemia and diabetes by applying the quasi-drug composition including the grape and Schisandra chinensis extract of the present invention.

As used herein, the term "quasi drug" refers to a fiber, rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a human or animal, has a weak action on the human body or does not directly act on the human body, Or non-machinery and the like, or any of the agents used for sterilization, insecticide and similar uses for the purpose of preventing infection, for the purpose of diagnosing, treating, alleviating, treating or preventing human or animal diseases. Means the goods used are not instruments, machines or devices, and the items used for the purpose of pharmacologically affecting the structure and function of humans or animals except those which are not devices, machines or devices. In addition, the quasi-drugs include external skin preparations and personal hygiene products.

When the grape and Schisandra chinensis extract of the present invention is used as an quasi-drug additive, the extract may be added as it is, or may be used together with other quasi-drugs or quasi-drug components, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined depending on the intended use.

The external preparation for skin is not particularly limited thereto, but may be preferably used in the form of an ointment, lotion, spray, patch, cream, powder, suspension, gel or gel. The personal hygiene products are not particularly limited, but preferably soap, cosmetics, wet wipes, tissue paper, shampoo, skin cream, face cream, toothpaste, lipstick, perfume, make-up, foundation, ball touch, mascara, eye shadow, Sunscreen lotions, hair care products, air freshener gels or cleaning gels. In addition, another example of the quasi-drug composition of the present invention is a disinfectant cleaner, shower foam, gagreen, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.

As another aspect, the present invention provides a feed additive or feed composition for the prevention or improvement of metabolic syndrome-related diseases, including grape and Schisandra chinensis extract as an active ingredient.

The grape and Schisandra chinensis extract, metabolic syndrome-related diseases are as described above.

Specifically, the grape and Schisandra chinensis extract of the present invention may be added to a feed additive or a feed composition comprising the feed additive for the purpose of preventing or improving metabolic syndrome-related diseases.

In the present invention, the term "feed additive" is a substance added to the feed for the purpose of various effects, such as supplementation of nutrients and weight loss prevention, improving the digestive availability of the fiber in the feed, improving the quality, prevention of reproduction disorders and improving conception, prevention of high temperature stress in summer Means. The feed additive of the present invention corresponds to a feed supplement under the Feed Control Act, and includes mineral preparations such as sodium bicarbonate, bentonite, magnesium oxide, and composite minerals, mineral preparations such as trace minerals such as zinc, copper, cobalt, and selenium, and kerosene. Vitamins such as vitamin E, vitamins A, D, E, nicotinic acid and vitamin B complex, protective amino acids such as methionine and lyric acid, protective fatty acids such as fatty acid calcium salt, probiotics (lactic acid bacteria), yeast culture, mold Probiotics such as fermented products, yeasts and the like may be further included.

As used herein, the term "feed" means any natural or artificial diet, one meal, or the like or any ingredient of the one meal for the animal to eat, ingest, and digest. Specifically, the feed comprising the composition for the prevention or treatment of metabolic syndrome-related diseases according to the present invention as an active ingredient can be prepared in a variety of forms known in the art, preferably rich feed, forage and / or special Feed may be included.

The rich feed includes seed fruits containing grains such as wheat, oats and corn, and by-products obtained by refining grains, bran, beans, fluids, sesame seeds, linseed, coco, etc., including rice bran, bran and barley bran. Fish soluble, which is a concentrate of fresh liquids obtained from fish residues, fish residues, and fish residues such as by-products such as seaweed, sweet potatoes, and potatoes, which are the remaining components of starch residue. soluble), meat meal, blood meal, milk powder, skim milk powder, milk from cheese, and whey, the balance of manufacturing casein from skim milk, dried foods such as dried whey, yeast, chlorella, and seaweed. This is not restrictive.

Forage, raw vegetables such as grasses, grasses, and green grass, fodder turnips, fodder beets, and root vegetables such as Lutherbearger, a type of turnip, raw grass, green grass crops, and grains Silage (silage), grasses, grasses, and dried hay, straws of breeders, and leaves of legumes, which are filled and fermented by lactic acid fermentation, are not limited thereto. Special feeds are supplemented with mineral feeds such as oyster shells and rock salts, urea feeds such as urea and its derivatives, diureide isobutane, and natural feed ingredients. Feed additives and dietary supplements, which are substances added in small amounts, are not limited thereto.

Feed composition comprising a composition for the prevention or treatment of the metabolic syndrome-related diseases according to the present invention can be prepared by adding a grape and Schisandra chinensis extract in a suitable effective concentration range according to various feed preparation methods known in the art.

The feed composition according to the present invention is not particularly limited as long as it is an individual for the purpose of preventing or treating metabolic syndrome disease, and any one may be applied. For example, it can be applied to any individual such as non-human animals such as monkeys, dogs, cats, rabbits, marmots, rats, mice, cows, sheep, pigs, goats, birds and fish.

As another aspect, the present invention provides a food composition for the prevention or improvement of metabolic syndrome-related diseases comprising grape and Schisandra chinensis extract as an active ingredient.

That is, the grape and Schisandra chinensis extract may be added to food compositions for the purpose of preventing or improving diseases related to metabolic syndrome, such as obesity, hyperlipidemia, hypertension, arteriosclerosis, hyperinsulinemia, diabetes, liver disease, and the like.

The food composition may comprise a food acceptable carrier.

Food compositions of the present invention include all forms of functional foods, nutritional supplements, health foods and food additives, and the like. It may be prepared in various forms according to known conventional methods.

When the grape and Schisandra chinensis extract is used as a food additive, the grape and Schisandra chinensis extract can be added as it is or used together with other food or food ingredients, and can be suitably used according to a conventional method. The mixed amount of the active ingredient can be determined suitably according to the purpose of use (prevention, health or therapeutic treatment). In general, the grape and Schisandra chinensis extract is added in an amount of 0.0001 to 1% by weight, preferably 0.001 to 0.1% by weight in the raw material composition in the manufacture of food or beverage. However, in the case of prolonged ingestion for health and hygiene purposes or for health control purposes, the amount may be used below the above range.

There is no particular limitation on the kind of food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates, etc. as additional components, as in the general beverage. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g, per 100 compositions of the present invention.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, And a carbonation agent used for the carbonated beverage. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention. In addition, the composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. The proportion of such pulp is not critical, but is generally selected in the range of 0.01 to 10 parts by weight per 100 parts by weight of the composition of the present invention. These components can be used independently or in combination.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention more specifically, but the scope of the present invention is not limited by these examples.

실시예 1: 포도 및 오미자 복합 추출물의 제조Example 1: Preparation of Grape and Schizandra Complex Extracts

1-1. Optimization of Grape Extract Extraction Conditions

In order to optimize the extraction conditions for the grape raw material, the conditions were first set using Campbell species processing by-products (juice packs). As a result of comparing and analyzing the yield and resveratrol content by extraction time and extraction temperature using ethanol as the extraction solvent, the highest yield and resveratrol content were obtained when extracted at 90 ° C for 2 hours using 80% ethanol. It was confirmed.

Based on the extraction conditions, the extraction yield and resveratrol content of each part (shell, seed, stem) of Campbell species and MBA species, which are the main varieties of Sangju and Yeongcheon, Gyeongbuk, were analyzed. The results are as shown in Tables 1 to 4 below.

Table 1

Comparison of Component Contents by Extraction Solvents of Grape By-Products at Room Temperature

Room temperature extraction / 24 hours	Yield (%)	Resveratrol Content
Room temperature extraction / 24 hours	Yield (%)	(%)	(mg / 100g)
40% EtOH	9.5	-	-
60% EtOH	11.9	0.002	2
80% EtOH	10.4	0.002	2
100% EtOH	10.5	0.003	3

TABLE 2

Comparison of Components by Extraction Solvents of Grape By-Products at 50 ℃

50 ℃ extraction / 24 hours	Yield (%)	Resveratrol Content
50 ℃ extraction / 24 hours	Yield (%)	(%)	(mg / 100g)
40% EtOH	11.6	0.001	One
60% EtOH	10.8	0.002	2
80% EtOH	11.1	0.003	3
100% EtOH	12.7	0.002	2

TABLE 3

Comparison of Components by Extraction Solvents of Grape By-products at 90 ℃

90 ℃ extraction / 24 hours	Yield (%)	Resveratrol content
90 ℃ extraction / 24 hours	Yield (%)	(%)	(mg / 100g)
40% EtOH	11.3	0.002	2
60% EtOH	14.4	0.003	3
80% EtOH	12.4	0.004	4
100% EtOH	11.5	0.003	3

Table 4

Comparison of Component Contents by Type and Region of Grape By-products

		Yield (%) (80% EtOH extraction)	Resveratrol Content
		Yield (%) (80% EtOH extraction)	(%)	(mg / 100 g)
MBA	skin	55	0.004	4
	strain	7	0.002	2
	stem	30	0.04	40
Campbell	skin	39	0.003	3
	strain	6	0.002	2
	stem	32	0.02	20

As can be seen in Table 1, both MBA and Campbell species were found to have high yields of peels and juices and resveratrol content. Therefore, according to the conditions set above, the extraction of Campbell or MBA grape skin and stem using 80% ethanol for 2 hours at 90 ℃ was set as the basic conditions of grape extract preparation.

Next, by varying the mixing ratio of the grape skin and stem used as the raw material of the grape extract, the content of Yield or Resveratrol was analyzed. The results are shown in Table 5 below.

Table 5

Setting the Optimal Mixing Ratio of MBA Species Raw Juice Extract and Stem

Juice Jelly: Stem	Yield (%)	Resveratrol Content
Juice Jelly: Stem	Yield (%)	(%)	(mg / 100 g)
1: 9	47.1	0.033	33
3: 7	38.6	0.030	30
4: 6	33.9	0.025	25
5: 5	31.6	0.023	23
7: 3	29.1	0.022	22

In consideration of the above analysis result and the amount of by-products generated after processing, the amount of the stem is relatively smaller than that of the juice gourd, so that the amount of the by-products is reduced, thereby considering the extraction yield and the resveratrol content. The mixing ratio of titration stems with utilization was determined. As a result, it was confirmed that the most economical and remarkable effect when the grape skin and grape stems are mixed in a 3: 1 to 4: 6 weight ratio.

1-2. Optimization of Extraction Conditions of Schizandra chinensis Extract

Schisandra chinensis was selected by using Schisandra chinensis from three major regions in Korea (Mungyeong, Jangsu, Inje). Considering the economics in terms of productive and productive conditions, experiments were conducted to set the conditions as similar as possible to the extraction conditions of grapes.

Thus, in case of having a difference in temperature, duration, etc. in the process, the economic efficiency of the process management is significantly lowered. Therefore, the extraction conditions were optimized using only the ethanol content as the extraction solvent condition.

Table 6

Comparison of Extraction Yield and Component Contents of Schizandra chinensis Extraction Conditions

		Yield (%)	Schizandrin content
		Yield (%)	(%)	(mg / 100 g)
Schisandra	Hydrothermal / 90 ℃ / 2 hours	49	0.5	494
	50% EtOH / 90 ℃ / 2 hours	45.2	0.8	805
	80% EtOH / 90 ℃ / 2 hours	43	0.9	870
	100% EtOH / 90 ℃ / 2 hours	42.4	0.9	850

In the remaining conditions except for hot water extraction, sizandrin content showed almost similar results, and extraction of Schizandra chinensis extract at 90 ° C. for 2 hours using 50% ethanol, the highest extraction yield condition, was performed under three conditions of ethanol content. It was set as the basic condition of.

1-3. Grape, Schisandra chinensis extract and complex extract preparation

Reflecting the optimized conditions, grape, Schisandra chinensis extract and complex extract were prepared.

Specifically, MBA grapes grown in Yeongcheon, Gyeongbuk, or grape juice and by-products of Campbell (Campbell) grapes grown in Sangju or Gimcheon, Gyeongbuk are purchased and cut and dried within 10% moisture content. The dried vineyards were ground and used for extract preparation. 200 g of each crushed grapes (shell: stem = 4 (80 g): 6 (120 g)) were taken, and 4000 mL of an 80% aqueous ethanol solution was added to each of the grapes, and extracted at 90 ° C. for 2 hours, and then concentrated under reduced pressure at 50 ° C. The concentrate was powdered by lyophilization or spray drying.

In addition, after purchasing and grinding Mungyeong dried Schizandra chinensis, 50 mL of 50% ethanol aqueous solution was added to 200 g of Schizandra chinensis, and extracted at 80 ° C. for 2 hours, and then concentrated under reduced pressure at 50 ° C.

The concentrate was lyophilized to finally obtain 60 g of grape extract and 116 g of Schisandra chinensis extract, respectively. Each extract was mixed and used in a set ratio to prepare the complex.

In order to set an appropriate ratio of grape extract and Schizandra chinensis extract, the amount of polyphenols was analyzed according to the ratio. Specifically, the grape extract and Schisandra chinensis extract were mixed in a weight ratio of 1: 1, 6: 1 or 10: 1, respectively, to determine the amount of polyphenols thereof. The results of the analysis are shown in Table 7 below.

TABLE 7

Determination of Polyphenols According to Weight Ratio of Grape Extract and Schisandra chinensis Extract

Grape: Schisandra chinensis (weight ratio)	Total Polyphenols (wt%)	Flavonoids (wt%)	Anthocyanin (% by weight)
1: 1	6.69	3.88	0.80
6: 1	10.22	6.15	1.13
10: 1	10.73	6.48	1.18

As can be seen in Table 7, the ratio of grapes was increased and the ratio of Schizandra was lowered compared to the case of mixing in a weight ratio of 1: 1, and when mixed in a ratio of 6: 1 and 10: 1 weight, the total amount of polyphenols extracted, Flavonoids and anthocyanin weight% was found to increase about 1.5 times.

1-4. Powdering through Spray-Drying of Grape and Schisandra chinensis Extracts

In order to powder the high sugar (Brix) grapes, Schisandra chinensis extract requires a spray drying process by mixing with excipients. The solid content of the concentrate prepared in Example 1-3 was measured, and maltodextrin (Samyang Corp. Genex) of the same amount as the solid content was added, and sprayed at 14,000 rpm, inlet temperature 130 ° C. and outlet temperature 80-90 ° C. Dried. After spray drying about 10 L of the excipient mixture, about 5 kg and 8 kg of grape and Schizandra chinensis powders were obtained, respectively.

실시예 2: C57BL/6 마우스를 이용한 포도 및 오미자 복합 추출물 식이급여Example 2: Dietary Supplementation of Grape and Schisandra chinensis Extract Using C57BL / 6 Mice

In order to measure the metabolic syndrome improvement effect of the grape and Schisandra chinensis extract and complex extract obtained in Example 1, the experiment was carried out as follows.

The experimental animal model was stabilized for 1 week while providing Lab-chow diet for 4 weeks old male C57BL / 6 mice, and randomly assigned 10 experimental animals per diet group. All experimental groups were based on a high-fat diet (Rad 17%, corn oil 3%, cholesterol 1%, wt / wt) and the extract treatment group added the grape and / or schizandra extracts prepared above to the diet.

The whole experimental group received the experimental diet under the conditions shown in Table 8 below for 12 weeks.

Table 8

	Diet	Salary Dietary Conditions
Control	Negative control (High-fat diet, HFD)	HFD
Experimental group	Grape single treatment group	HFD + Grape Extract 0.5% (wt / wt)
	Schisandra monotherapy group	HFD + Schisandra extract 0.05% (wt / wt)
	Grape Schizandra Complex Treatment Group	HFD + Grape Extract 0.5% (wt / wt) + Schizandrae Extract 0.05% (wt / wt)

The animals were kept in a controlled life cycle with a 12-hour light intensity illumination from 6 to 18 hours under constant temperature (25 ° C) and constant humidity (50%), and were housed in individual stainless cages. , Diet and drinking water were supplied as ad libitum. The body weight and dietary intake were measured weekly. After 12 weeks of fasting for 12 hours, blood was collected from the abdominal inferior vena cava and organ tissues were collected.

실시예 3 : 체중, 체지방 중량 및 지방조직 세포 크기 측정Example 3 Measurement of Body Weight, Body Fat Weight and Adipose Tissue Cell Size

The weight of body fat tissue collected in the animal experiment conducted in Example 2 was compared for each experimental group. As a result, the weight increase of the grape Schizandra complex group was significantly (p <0.05) compared to the control and Schizandra single group (FIG. 1).

In addition, a total of 6 areas of white adipose tissue (epidermis fat, peripartum fat, posterior abdominal fat, mesenteric fat, subcutaneous fat, scapula fat) were extracted and measured. p <0.05) it was confirmed that the weight is reduced (Fig. 2).

In addition, it was confirmed that the size of the adipose tissue cells of the epididymal fat was the smallest in the grape Schizandra complex group, and the size of the fat cells in the control group was the largest (FIG. 3).

On the other hand, there was no significant difference between the experimental groups in terms of dietary intake.

실시예 4 : 대사증후군 관련 아디포카인 농도 및 유전자 발현도 측정Example 4 Measurement of Adipocaine Concentration and Gene Expression of Metabolic Syndrome

Plasma was separated from the blood collected in the animal experiment conducted in Example 2 to measure the expression level of adipocaine and adipose gene.

As a result, the level of adipocaine present in the plasma was consistent with the weight gain or body fat weight loss confirmed in Example 3, and significantly decreased Leptin and PAI-1 concentrations in the grape Schizandra complex treatment group compared to the control group. Confirmed. In addition, it was confirmed that the levels of plasma TNFα, IL-6, MCP-1 were also reduced in the grape schizandra complex treatment group (FIG. 4). Resistin was not found to be statistically significant, but it was found to be 24% lower than that of the control group.

The above results show that grape Schizandra extract is effective in reducing fat mass. Therefore, in order to determine whether the grape Schizandra complex extract affects adipogenesis and, if so, the mechanism of adipocytes, the expression levels of fat synthesis-related genes and inflammatory genes in adipose tissues were identified. .

The mRNA expression levels of the transcriptional factor PPARγ (peroxisome proliferator activated receptor γ) and the major target genes for adipocyte formation, FAS (fatty acid synthase), ME (malic enzyme), and LPL (lipoprotein lipase), were expressed in the control group of grape Schizandra chinensis. Significantly lower than that. In addition, mRNA expression of NF-κB, inflammatory cytokine genes, TNFα, IL-6 and MCP-1, which are inflammatory factors in adipose tissue, was also significantly decreased in the group of grape Schizandra chinensis. It was confirmed (Fig. 5).

실시예 5 : 포도 및 오미자 복합 추출물의 간조직 지질축적 억제 효과Example 5 Hepatic Lipid Accumulation Inhibitory Effects of Grape and Schizandra Complex Extracts

Changes in lipid concentrations of liver tissue collected in the animal experiments performed in Example 2 were confirmed.

As a result of measuring free fatty acid, triglyceride, and cholesterol concentrations, no significant change was observed in the grape single intake group compared to the control group, but a significant decrease was observed in the experimental group in which the grape schizandra complex extract was ingested (FIG. 6 and FIG. 7).

On the other hand, the amount of expression of fatty acid synthesis and fatty acid oxidation related genes affecting the lipid accumulation of liver tissue was analyzed (Fig. 8). Expression of CD36, FAS, ACC1, SCD1, ME and LPL, which are genes related to fatty acid influx and fatty acid biosynthesis, was significantly reduced in the grape schizandra complex treated group.

In addition, the expression levels of HMGR and ACAT, cholesterol regulatory genes, as well as fatty acids were reduced. As in adipose tissue, it was confirmed that gene expression of inflammatory genes NF-κB, TNFα, IL-6 in liver tissues was significantly reduced in the grape schizandra complex treatment group (FIG. 9).

These results indicate that fatty acid influx, fatty acid and cholesterol biosynthesis reduction in liver tissue can improve the lipid accumulation and fat globule formation of liver tissues.

실시예 6 : 대사증후군 동물 모델을 이용한 포도 오미자 복합 추출물의 최적 비율 설정Example 6: Setting the Optimal Ratio of Grape Schizandra Complex Extract Using Metabolic Syndrome Animal Model

Through the above results, it was confirmed that the grape schizandra complex extract has an effect on metabolic syndrome, particularly fat accumulation and production, and to determine the optimal ratio of the grape extract and Schizandra extract constituting the complex extract. To this end, animal experiments were conducted using a db / db mouse model, which is an animal model for the study of type 2 diabetes and complications.

Specifically, four weeks-old male C57BL / KsJ- db / db mice were stabilized for one week while providing a Lab-chow diet, and ten experimental animals were randomly assigned to each group. All experimental groups were based on the normal diet (AIN-76 diet), and the extract treatment group added the grape schizandra complex extract prepared by mixing grape extract and Schizandra extract at different ratios.

The experimental group of animals was distinguished as shown in Table 9 below.

Table 9

	Diet	Salary Dietary Conditions
Control	Negative control (Normal diet, ND)	ND (5% corn)
Experimental group	HGO group (High Grape and Omija extract)	ND + Grape Extract 0.5% + Schizandra Extract 0.05%
Experimental group	LGO group (Low Grape and Omija extract)	ND + Grape Extract 0.3% + Schizandra Extract 0.05%

The experimental animals were kept in the life cycle from 6 to 18 o'clock under the conditions of constant temperature (25 ° C) and constant humidity (50%), and were housed in individual stainless cages. libitum). The diet was stored at 4 ° C. and weekly body weight and dietary intake were measured. After 7 weeks of fasting for 12 hours, blood was collected from the inferior vena cava and organ tissues were collected.

실시예 7 : 체지방 중량 및 지방산 대사 관련 효소 활성도 측정Example 7 Determination of Enzyme Activity Related to Body Fat Weight and Fatty Acid Metabolism

In the animal experiment conducted in Example 6, a total of 6 areas of white adipose tissue (epidermis fat, renal periphery fat, posterior cavity fat, mesenteric fat, subcutaneous fat, scapula fat) were extracted and measured, and the composite extract treatment group ( HGO and LGO), scapula fat, subcutaneous fat and mesenteric fat were significantly reduced compared to the control group. Accordingly, it was confirmed that the weight of the total white adipose tissue was also significantly reduced in the composite extract treatment group compared to the control (Figs. 10 and 11).

On the other hand, fatty acid metabolism-related enzyme activity in the liver tissue obtained in the animal experiments performed in Example 6 was measured. As a result, it was confirmed that the activity of fatty acid synthase FAS and G6PD in liver tissue of the composite extract treatment group was significantly decreased compared to the control, whereas the activity of β-oxidation related enzyme, fatty acid oxidase, was significantly lower than that of the control group. It was found that the increase was significantly (Fig. 13). Accordingly, as can be seen in Figure 12, it was confirmed that a large number of lipid droplets (lipid droplet) only in the liver tissue of the control group.

From the above description, those skilled in the art will appreciate that the present invention can be implemented in other specific forms without changing the technical spirit or essential features. In this regard, the embodiments described above are to be understood in all respects as illustrative and not restrictive. The scope of the present invention should be construed that all changes or modifications derived from the meaning and scope of the following claims and equivalent concepts rather than the detailed description are included in the scope of the present invention.

Claims

Composition for the prevention or treatment of metabolic syndrome-related diseases comprising grape and Schizandra complex extract as an active ingredient.
The composition of claim 1, wherein the extract is an extract extracted with a solvent selected from the group consisting of water, alcohols having 1 to 4 carbon atoms, and mixed solvents thereof.
The composition of claim 1, wherein the grape extract is obtained from a mixture of grape skin and grape stems.
The composition of claim 3, wherein the grape extract is obtained from a mixture of grape skins and grape stems in a 0.5 to 4: 1 weight ratio.
The composition of claim 1, wherein the complex extract comprises grape extract and Schisandra chinensis extract in a weight ratio of 3 to 15: 1.
The composition of claim 1, wherein the metabolic syndrome related disease is at least one disease selected from the group consisting of obesity, hyperlipidemia, hypertension, arteriosclerosis, hyperinsulinemia, diabetes and liver disease.
According to claim 6, wherein the liver disease is non-alcoholic fatty liver, alcoholic fatty liver, non-alcoholic steatohepatitis, terminal fibrotic liver disease, non-viral chronic hepatitis, cirrhosis and liver cancer is one or more diseases selected from the group consisting of, Composition.
The composition of claim 1, wherein the composition comprises any one or more of the following features:

a) inhibiting adipocaine expression or secretion;

b) inhibiting fat biosynthetic gene expression;

c) inhibiting adipocyte-forming gene expression;

d) inhibiting inflammatory gene expression;

e) inhibition of gene expression associated with fatty acid influx;

f) inhibition of fatty acid biosynthetic gene expression; And

g) inhibition of cholesterol regulatory gene expression.
The composition of claim 1, wherein the composition is characterized by weight loss of body fat.
The composition of claim 1, wherein the composition has a feature of inhibiting lipid accumulation in liver tissue.
A method of treating a metabolic syndrome related disease, comprising administering the composition of any one of claims 1 to 10 to a subject other than a human in need thereof.