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WO2015030293A1 - Composition contenant un extrait composite de raisin et de schisandra chinensis pour la prévention ou le traitement de maladies associées au syndrome métabolique - Google Patents

Composition contenant un extrait composite de raisin et de schisandra chinensis pour la prévention ou le traitement de maladies associées au syndrome métabolique Download PDF

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WO2015030293A1
WO2015030293A1 PCT/KR2013/009339 KR2013009339W WO2015030293A1 WO 2015030293 A1 WO2015030293 A1 WO 2015030293A1 KR 2013009339 W KR2013009339 W KR 2013009339W WO 2015030293 A1 WO2015030293 A1 WO 2015030293A1
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grape
composition
extract
liver
metabolic syndrome
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Korean (ko)
Inventor
김혜진
심재석
박석준
신동주
최명숙
조수정
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CJ CheilJedang Corp
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/79—Schisandraceae (Schisandra family)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • 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.
  • 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.
  • 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.
  • 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. .
  • 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.
  • Type I insulin-dependent diabetes mellitus
  • IDDM insulin-dependent diabetes mellitus
  • 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.
  • NIDDM non-insulin-dependent diabetes mellitus
  • 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
  • type 1 diabetes is currently the most common method of insulin injection.
  • PPAR- ⁇ 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.
  • 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.
  • 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.
  • fatty liver 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.
  • the present inventors have no side effects on metabolic syndrome-related diseases including hyperlipidemia, diabetes mellitus, liver disease, and the like.
  • metabolic syndrome-related diseases including hyperlipidemia, diabetes mellitus, liver disease, and the like.
  • 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.
  • 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.
  • white adipose tissue epidermal fat, periphery fat, posterior cavity fat, mesenteric fat, subcutaneous fat, scapular fat
  • 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.
  • FIG. 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.
  • adipose tissue 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.
  • HGO high grape and omija extract
  • LGO low grape and omija extract
  • FIG. 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.
  • FIG. 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.
  • 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.
  • grapes can be purchased commercially, or can be used collected or grown in nature.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • dry grape pulverized product prepared by cutting the grape skin and stem of grape juice by-products and dried to within 10% moisture content.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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
  • the gene associated with inflammatory may be NF- ⁇ B, TNF ⁇ , IL-6 or MCP-1, but is not limited thereto.
  • liver tissue 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.
  • the fatty acid oxidation related gene may be a ⁇ -oxidaion related gene.
  • composition of the present invention may be a composition comprising any one or more of the following features a) to g).
  • 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) - ⁇ , 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.
  • 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. .
  • 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.
  • composition of the present invention can treat or prevent liver disease through reduced expression of inflammatory genes in adipose tissue or liver tissue.
  • 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.
  • hypolipidemia 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.
  • 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.
  • 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.
  • hypoinsulinemia 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.
  • 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.
  • diabetes 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.
  • 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).
  • 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.
  • HGO high grape and omija extract
  • grape extract LGO low grape and omija extract
  • 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.
  • 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.
  • 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.
  • non-viral refers to an illness caused by alcoholic, non-alcoholic (obesity, diabetes, hyperlipidemia) or other (toxic, pollution, drug, neurological, overworked) causes.
  • 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.
  • 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.
  • 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.
  • ADH alcohol dehydrogenase
  • MEOS microsomal ethanol oxidizing system
  • ALLDH dehydrogenase
  • acetaldehyde may be toxic and damage liver cells.
  • superoxide (O) in the process of alcohol metabolism is activated by cytochrome P450-2E1 (CYP2E1; cytochrome P450 2E1).
  • ROS reactive oxygen species
  • H 2 O 2 hydrogen peroxide
  • peroxynitrite peroxynitrite
  • 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.
  • chronic liver disease includes chronic hepatitis, cirrhosis, and liver cancer
  • cirrhosis also called cirrhosis
  • 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.
  • 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.
  • 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.
  • AFP alpha-fetoprotein
  • liver diseases may vary from patient to patient, but if the disease becomes chronic, the disease progresses gradually to hepatitis, cirrhosis, liver cancer.
  • 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.
  • 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.
  • 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.
  • treatment refers to any action by which administration of a composition according to the invention improves or advantageously alters the symptoms of the diseases.
  • the composition of the invention is a pharmaceutical composition.
  • the composition may comprise a pharmaceutically acceptable carrier.
  • composition comprising a pharmaceutically acceptable carrier may be in a variety of oral or parenteral formulations.
  • 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.
  • 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.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • 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.
  • composition of the present invention is administered in a pharmaceutically effective amount.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the quasi-drugs include external skin preparations and personal hygiene products.
  • the grape and Schisandra chinensis extract of the present invention When 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the grape and Schisandra chinensis extract When 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).
  • 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.
  • the amount may be used below the above range.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the extraction conditions were optimized using only the ethanol content as the extraction solvent condition.
  • 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.
  • the concentrate was powdered by lyophilization or spray drying.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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 TNF ⁇ , 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.
  • 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. .
  • mRNA expression levels of the transcriptional factor PPAR ⁇ peroxisome proliferator activated receptor ⁇
  • FAS fatty acid synthase
  • ME malic enzyme
  • LPL lipoprotein lipase
  • 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.
  • animal experiments were conducted using a db / db mouse model, which is an animal model for the study of type 2 diabetes and complications.
  • mice 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.
  • 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.
  • Example 6 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).
  • fatty acid metabolism-related enzyme activity in the liver tissue obtained in the animal experiments performed in Example 6 was measured.
  • 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 ⁇ -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.

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Abstract

L'invention concerne une composition contenant, comme ingrédient actif, un extrait composite de raisin et de Schisandra chinensis, pour prévenir ou traiter des maladies associées au syndrome métabolique; une méthode de prévention ou de traitement de maladies associées au syndrome métabolique utilisant cette composition; une composition alimentaire; un additif pour l'alimentation animale ou une composition pour l'alimentation animale; et une composition médicinale contenant un extrait composite de raisin et de Schisandra chinensis pour prévenir ou soulager des maladies associées au syndrome métabolique. Selon l'invention, il a été confirmé que l'extrait composite de raisin et de Schisandra chinensis peut réduire la masse de graisse corporelle, et plus spécifiquement, la masse de tissu adipeux blanc, ce qui permet de réduire le gain de poids total et contrôler divers biomarqueurs et adipokines associés au syndrome métabolique, et d'être ainsi efficace dans la prévention et le traitement du syndrome métabolique, notamment l'hyperlipémie, le diabète et les maladies du foie. L'invention présente ainsi l'avantage de fournir cette composition qui contient, comme ingrédient actif, l'extrait composite de raisin et de Schisandra chinensis pour la prévention et le traitement de maladies associées au syndrome métabolique. L'invention peut également être appliquée à la composition alimentaire, à l'alimentation du bétail, ou à un additif alimentaire pour prévenir ou soulager des maladies associées au syndrome métabolique.
PCT/KR2013/009339 2013-08-30 2013-10-18 Composition contenant un extrait composite de raisin et de schisandra chinensis pour la prévention ou le traitement de maladies associées au syndrome métabolique Ceased WO2015030293A1 (fr)

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KR20220121287A (ko) 2021-02-24 2022-09-01 성이바이오(주) 가래 추출물 및 오미자 추출물의 복합물을 포함하는 체지방 감소 또는 피부 미백용 조성물
KR20230099719A (ko) 2021-12-27 2023-07-05 고려대학교 산학협력단 토마토케첩, 토마토 페이스트, 또는 이의 추출물을 유효성분으로 포함하는 대사증후군 관련 질환 예방 또는 치료용 조성물
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KR20240102057A (ko) 2022-12-23 2024-07-03 농업회사법인 현대에프엔비 주식회사 아이스플랜트 분말을 포함하는 대사증후군 개선용 조성물

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