KR101672274B1 - Compositions comprising a Viola Herba extract, or an extract of Viola Herba, Persicae Semen, Cinnamomi Ramulus, and Glycyrrhiza spp. for the prevention or treatment of lipid-related cardiovascular diseases and obesity - Google Patents

Abstract

The present invention relates to a method for the prevention or treatment of lipid-related cardiovascular diseases or obesity, including a Viola Herba extract, or a combination extract of Persicae Semen, Cinnamomi Ramulus, and Glycyrrhiza spp. A pharmaceutical composition for food addition, and a method for treating lipid-related cardiovascular diseases or obesity comprising the step of administering the pharmaceutical composition to an individual in need thereof.
INDUSTRIAL APPLICABILITY The extract of the magnetism designation or the magnetization designation of the present invention is effective for the prevention or treatment of lipid-related cardiovascular diseases or obesity due to the effects of weight loss, reduction of body fat content, lowering of total cholesterol and blood pressure, Can be used.
In addition, the magnetization designation extract reduced the incidence of atherosclerotic lesions in atherosclerotic model mice; And lipid accumulation inhibitory effect in liver tissue and blood, it can be effectively used for preventing or treating arteriosclerosis.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for preventing or treating lipid-related cardiovascular diseases and obesity, which comprises a magnetized design extract, a magnetization designation, a donor, an adhesive, and a licorice complex extract , and Glycyrrhiza spp. for the prevention or treatment of lipid-related cardiovascular diseases and obesity}

The present invention relates to a pharmaceutical composition for prevention or treatment of lipid-related cardiovascular diseases or obesity comprising a magnetized design extract, or a combination extract of a magnetization designator, a donor, an adhesive, and licorice; And a method of treating lipid-related cardiovascular disease or obesity comprising the step of administering the composition to a subject in need thereof.

The present invention also relates to a composition for the addition of a food for preventing or ameliorating lipid-related cardiovascular diseases or obesity comprising the above extract or a complex extract.

Dietary fat intake in Korean adults has steadily increased over the past decade. According to the Korean National Health and Nutrition Examination Survey, the prevalence of obesity based on the BMI in 2010 was 36.3% for men and 24.8% for women, especially for men, which has steadily increased over the past decade. According to the 2005 survey results, the rate of calorie intake from the province in Korea exceeds 20%. In particular, the increase in the intake of animal food is prominent, and the total fat intake and the saturated fatty acid intake are increasing, indicating that intake of dietary fat, type, and fatty acid intake level are important determinants of blood lipid levels. These changes in eating habits are known to be associated with an increased risk of cardiovascular disease. In addition, the National Statistical Office (NSO) data released in September 2012 showed that cancer was the leading cause of death in Korea, followed by cerebrovascular disease in the second, cardiovascular disease in the third, circulatory diseases such as arteriosclerosis, myocardial infarction and stroke It is known to be more affected by diet than other chronic diseases. Cholesterol, triglyceride, hypertension, smoking, thrombosis, diabetes and obesity are known as risk factors. Among them, blood cholesterol and hypertension are major risk factors of arteriosclerosis and myocardial infarction. Maintaining the blood cholesterol concentration to be normal can be said to be important in preventing the onset of the diseases.

On the other hand, when cholesterol is appropriately controlled in the body, cholesterol accumulation does not occur in plasma and tissues. However, when the level of cholesterol in the body is increased, hypercholesterolemia occurs, abnormalities in the regulation of cholesterol metabolism occur, (LDL-cholesterol), and high-density lipoprotein-cholesterol (HDL-cholesterol). In particular, low-density lipoprotein-cholesterol (LDL-cholesterol) is known to be a risk factor for cardiovascular disease. The increase in blood triglyceride concentration decreases the concentration of high-density lipoprotein-cholesterol (HDL-cholesterol) (Chylomicron), a lipoprotein particle composed mainly of Triglyceride, is known to be a major cause of coronary artery disease. In addition, blood lipids are more likely to pass through endothelial cells than other lipids, leading to atherosclerosis, and the rapid rise of postprandial triglycerides is known to be closely related to the occurrence of stroke. On the other hand, HDL-cholesterol (HDL-cholesterol) is known to be a preventive factor for cardiovascular diseases because it acts to remove cholesterol from blood vessel walls. Therefore, in order to prevent or treat various diseases caused by lipid metabolism abnormality, it is desirable that the blood lipid composition comprising triglyceride, cholesterol, phospholipids, and free fatty acid It is important to keep the components at their normal concentrations.

Currently, dietary fiber, saponin, vitamin C, vitamin E, and essential fatty acids are used for the prevention and treatment of lipid metabolic diseases. And essential amino acids. Dietary therapy, however, is accompanied by mental illness due to dietary restrictions, making it difficult to continue for a long period of time. In addition to the above-mentioned dietary therapy, drug therapy has been used for the treatment of lipid metabolism diseases. Such lipid-lowering drugs have to be administered for a lifetime, and there is a risk of complications such as elevated liver function and myocardial disease, There is a problem that medicines are difficult to treat when they are increased more than three times. Therefore, there is a need for useful active ingredients that can treat lipid-related cardiovascular diseases and obesity among natural ingredients.

Obesity, or obesity, is a term that refers to the excess weight of a person's body weight. In a pathologic sense, it refers to a body mass index (BMI) of 30 or more as defined by the World Health Organization (WHO) If it is 25 or more, it is diagnosed as obesity. In most cases, weight means more than normal, but even if you do not have a lot of weight, the proportion of fat in your body is high. Obesity is an accumulation of excess fat in the body, which increases the number of adipocytes in the adipose tissue or increases the size of the adipocyte. Obesity may not be a problem in itself, but it has serious social problems and secondary complications caused by excessive fat. For example, obesity is becoming more and more important as it causes major diseases such as hypertension, hyperlipidemia, heart disease, diabetes, arteriosclerosis, fatty liver, joint disorders, arthritis, sexual dysfunction and cancer. If the body weight is 20% higher than normal weight, the likelihood of developing diabetes increases to 10 times that of normal people. In addition, cardiovascular and pulmonary function may be impaired and life expectancy may be shortened. Complex factors such as hypertension, diabetes, hypercholesterolemia, and atherosclerosis may put pressure on the heart function and lead to heart failure and sudden death. In women, the incidence of endometrial cancer is increased, and cholelithiasis is more likely to occur. Men are more likely to develop colon cancer and prostate cancer. In addition, as the weight increases, people can not help but be conscious of the gaze that they are looking at, and if the obsession about it becomes worse, the symptoms of avoiding people and living alone are generated. In addition, the inferiority feeling that comes from the body affects the self by losing confidence in his life.

In order to prevent obesity and maintain a healthy weight, balanced diet and regular exercise should be maintained throughout the lifetime. In particular, fat cells can be reduced in size once they are made, but it is impossible to remove them naturally and it is left permanently in the human body, so it is important to prevent obesity from beginning. Therefore, weight loss can be reduced primarily by reducing the amount of calories consumed and increasing activity and exercise.

However, as described above, since the fat cells once formed can not be removed, there are cases where a drug such as diet intake and fat absorption reduction are taken. However, such diet drugs can cause side effects such as cardiovascular disease and stroke, such as hypertension, and frequently increase in weight again when stopped. In the case of severe obesity, surgical treatment can be performed. Such surgery is performed by surgery to remove fat or gastroplasty or gastric banding to limit the amount of food that can be digested by the body.

Current therapeutic agents for obesity include appetite suppressants, heat metabolism promoters, digestion inhibitors, and hormone regulators that reduce food intake, control body metabolism, and increase body heat response. There are adrenergic, serotonergic, and adrenaline-serotonin drugs in the appetite suppressant, but serotonin drugs have been banned due to the side effects of heart valves. The thermodynamic stimulants include the ephedrine-caffeine complex and the adipocyte 3 receptor agonist, and digestion inhibitors include lipase inhibitors typified by Xenical and low-fat food additives called Olestra. Many of the medications used to date have been reported to cause side effects such as yo-yo phenomenon, anorexia, headache, hypertension, diabetes, diarrhea, abdominal distension and abdominal pain. It is interpreted as a result of unverified products. Therefore, the development of new natural materials using herbal medicine resources, which have proven to be safe and have less side effects, is an ongoing challenge in the current era.

Under these circumstances, the present inventors have made efforts to find natural products with low side effects while having an effect of preventing or treating lipid-related cardiovascular diseases or obesity. As a result, it has been found that the extracts of Magnetization Designation, Magnetization Designation, (LDL-cholesterol), increased HDL-cholesterol (HDL-cholesterol), increased fat-soluble protein (HDL-cholesterol), decreased triglyceride Induced adiponectin mRNA expression, UCP-2 (mitochondrial uncoupling protein-2) mRNA expression, and blood pressure-lowering effect, and completed the present invention.

It is an object of the present invention to provide a pharmaceutical composition for prevention or treatment of lipid-related cardiovascular diseases or obesity comprising a magnetization-designated extract or a magnetization designation, flavor, anchovy, and licorice complex extract.

Another object of the present invention is to provide a method for producing a magnetized design extract, Or a composition for the prevention or amelioration of lipid-related cardiovascular diseases or obesity comprising a combination of a magnetization designation, a donor, an agate, and a licorice complex.

It is another object of the present invention to provide a method for treating lipid-related cardiovascular diseases or obesity comprising the step of administering the pharmaceutical composition to a subject in need thereof.

In one embodiment for achieving the above object, the present invention relates to a method for producing an extract of Viola Herba or an extract of Persicae Semen, Cinnamomi Ramulus, and Glycyrrhiza and a pharmaceutical composition for the prophylaxis or treatment of lipid-related cardiovascular diseases or obesity.

The inventors of the present invention conducted studies on various natural products in order to find a natural product having a side effect of preventing or treating lipid-related cardiovascular diseases or obesity while having a few side effects. In the study of Vitala Herba extract or Persicae Semen, , Cinnamomi Ramulus, and licorice ( Glycyrrhiza spp.) complex extracts.

And extracting the mixture of the magnetization designation, the magnetization designation, the magnetorization designation, the donor, the binding agent and the licorice composition with water to prepare the magnetization designation extract or the magnetization designation, As a result of the test for the prevention or treatment of cardiovascular disease or obesity of the combined extracts, the above-mentioned Magnetized Designed Extract or Magnetization Designated, Dietary, Gastric, and Licorice Composite Extracts showed effects of inhibiting weight gain, suppressing dietary intake, Decreased triglyceride, decreased LDL-cholesterol, increased HDL-cholesterol, increased expression of adiponectin mRNA in adipose tissue, expression of UCP-2 mRNA And decreased blood pressure, respectively.

In addition, when the effect of preventing or treating arteriosclerosis of the magnetically fixed extract was tested using a mouse model of atherosclerotic disease model in which the apolipoprotein E (ApoE) gene was deficient, the above magnetized designated extract inhibited weight gain; Inhibiting liver weight gain; Decreased fat cell size and lipid deposition in liver tissue; Reduced incidence of atherosclerotic lesions; Total cholesterol, LDL-cholesterol, Triglyceride and Glucose levels decreased; Increased AMPK activity; And inhibited the expression of FAS and SREBP-1 protein.

Therefore, it has been found that the magnetized design extract, the magnetization designation agent, the gherkin and the licorice complex extract can be used for prevention, treatment or improvement of lipid-related cardiovascular diseases or obesity.

The term "lipid-related cardiovascular disease" in the present invention means a vascular disease, a cardiac disease or a cerebrovascular disease of the circulatory system, and specifically refers to a disease caused by atherosclerosis, hypertension, myocardial infarction, stroke, hyperlipidemia, But is not limited to, one or more selected from the group consisting of cardiac arrhythmia, heart failure, angina pectoris, endocarditis, heart valve disorders, conduction disorders, and ischemic cerebrovascular disease.

The term "vascular disease of the circulatory system" in the present invention means a general case of a disease occurring in various circulatory organs including the heart involved in blood circulation and the small circulatory system.

In the present invention, the term "heart disease" refers to a heart-related disease that is responsible for blood supply to the human body, and refers to ischemic heart disease, cardiac arrhythmia, heart failure and the like collectively. Ischemic heart disease typically refers to angina or myocardial infarction, which is an acute or chronic cardiac disorder caused by reduced or stopped blood supply to the myocardium as the disease progresses. Other cardiac diseases include endocarditis, heart valve disorders, conduction disturbances, cardiac arrhythmia, or heart failure. In particular, heart failure means that the heart can not rescue the blood that returns to the heart through the venous system.

The term "cerebral vascular disease" in the present invention means a disease caused by sudden onset of cerebral vasculature resulting in cerebral dysfunction, and in some cases, hemorrhagic and vascular But is not limited to, ischemic cerebrovascular disease, in which the blood flow is deteriorated or clogged.

The term "obesity " in the present invention means an excess of body fat, which means that the body mass index is clinically 25 in Korea and 30 or more according to the World Health Organization (WHO). Generally, it means that the body weight is higher than the normal value. However, when the body fat percentage of the body composition is high, even if the body weight does not go out, it is diagnosed as obesity.

In the present invention, the term "anti-obesity " is used to mean prevention, treatment, or improvement of obesity.

The term "magnetization designation ( Viola Herba "is a viola of Violaceae ( Viola mandshurica ) or Violaceae ( Viola yezoensis ) of the whole plant (outpost). The magnetization design has a slight peculiar odor and irritation, and the taste is very high and the quality is low. In addition, there is the efficacy of detoxifying cyanobacterium which acts on the bloodstream to lower the heat and detoxify the poison. Ingredients include saponin, flavonoid compounds, cerotic acid, and unsaturated fatty acids. However, there is no information on the effect of the magnetically labeled extract on lipid-related cardiovascular disease or anti-obesity effect.

The term "degree (Persicae Semen)" of the present invention peach tree of the rose family (Prunus persica), or acid copies (Prunus davidiana ) seeds or seeds and branches. There is almost no smell, it is like oil, the taste is worn, and the quality is the same as it is not shifted to one side. It is applied to lower abdominal pain, menstrual irregularity, bruise abscess, lung abscess and appendicitis. It is effective for constipation because it is rich in fat and lubricates the intestine. It is effective for skin itching, dryness, spots and freckles It is used. It relieves sudden heartburn pain.

The term " Cinnamomi Ramulus "of the present invention refers to a branch of a tree belonging to the genus Cinnamomum, It means tree bark. Specifically, a camphor tree ( Cinnamomum cassia or Cinnamomum loureirii ) or bark, but is not limited thereto. It is known that the pharmacological action is to suppress the development of Escherichia coli, Bacillus thuringiensis, Staphylococcus aureus, Staphylococcus aureus and pneumococcal strains, suppress the influenza virus, and diuretic action.

The term "licorice" of the present invention means perennial herbaceous plants belonging to the genus Glycyrrhiza . Specifically, the licorice is Glycyrrhiza glabra , Glycyrrhiza uralensis), glycyrrhizin Liza inflation rata (Glycyrrhiza inflata), glycyrrhizin Lisa Farley di Flora (Glycyrrhiza pallidiflora , Glycyrrhiza squamulosa , Glycyrrhiza echinata , and the like. In the present invention, the roots or stem parts of licorice root can be used with their husks attached or peeled off.

The term "extract" in the present invention means an extract obtained by extracting a herbal medicine with an appropriate extraction solvent, and is not limited thereto. Examples thereof include an extract obtained by extraction treatment, a diluted solution or concentrate of the extract, Lt; RTI ID = 0.0 > refined < / RTI >

In the present invention, the extract may be prepared by extracting with an extraction solvent or extracting with an extraction solvent, followed by fractionation with a fraction solvent. The extraction solvent may be, but is not limited to, water, an organic solvent or a mixed solvent thereof. The organic solvent may be an alcohol having 1 to 4 carbon atoms, a polar solvent such as ethyl acetate or acetone, hexane or dichloromethane Non-polar solvents or mixed solvents thereof may be used. Further, water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof may be preferably used. In one embodiment of the present invention, an extract was prepared using water as the solvent.

In the present invention, the term " complex extract " Refers to an extract obtained by mixing a mixture of doenjang, guinea, and licorice at a weight ratio of 1: 1 to 1: 5 and extracting with an extraction solvent. The mixing ratio is preferably 1: 2 to 1: 4, and most preferably 1: 3, but is not limited thereto. In addition, the mixture of the above-described mannitol, ghatti, and licorice may be mixed in a weight ratio of 1: 1: 1 to 6: 2: 1, specifically, 3: 2: 2 But is not limited thereto.

The magnetization designation extract, magnetization designation, flavor, binding agent, and licorice complex extract may be produced by a common extraction method, separation and purification method known in the art. The extraction method may be, but not limited to, hot water extraction, hot water extraction, cold extraction, reflux cooling extraction, or ultrasonic extraction.

In the present invention, the whole plant excluding the whole plant excluding the bark of the broiler tree and the licorice bark is extracted from the whole plant designated as the magnetized design extract, , Although other parts may also be used.

According to one specific production example of the present invention (Production Example 1), the magnetically-designated extract of the present invention was extracted by adding 5 to 20 times the solvent to the specified dry weight of magnetization. The extracts of doenjang, mackerel, and licorice were mixed and extracted with hot water at a ratio of 3, 2, and 2. The water extracts were prepared by adding a mixture of 3, 5, and 75% by weight of the mixture extract of licorice, licorice, licorice,

According to one embodiment of the present invention (Embodiment 2), when the extract designated as the high-fat diet method is administered, the body weight decreases from 11 weeks of age when compared to the high fat diet, and the mixed extract of the mandarin- (Fig. 1 and Table 1). ≪ tb >< TABLE >

According to another embodiment of the present invention (Example 3), it was confirmed that the magnetically-designated extract had an effect of suppressing body weight loss and dietary intake, and the combined extracts of magnetization designation, And dietary intake (Table 2).

According to another embodiment of the present invention (Example 4), the effects of the designated magnetization designation, magnetization designation, physician, licorice and licorice complex extract on blood lipid were examined. As a result, , The concentration of total cholesterol and low - density lipoprotein - cholesterol decreased and the concentration of high - density lipoprotein - cholesterol increased. (Table 3). In addition, the concentration of glucose, total cholesterol, triglyceride, low density lipoprotein - cholesterol and high density lipoprotein -

According to another embodiment of the present invention (Example 5), adiponectin mRNA expression, which is involved in glucose metabolism and lipolysis, was markedly increased when a high-fat diet, licorice extract and licorice extract were administered , And the expression of adiponectin mRNA was also increased when the high-fat diet was administered with the combination of the magnetization designation, doenjang, ginseng and licorice (Fig. 2).

In addition, UCP-2 mRNA expression was increased when the high-fat diet extract was used or the mixed extract of Phellinus linteus, licorice and licorice was used. In the case of UCP-2 mRNA expression, (Fig. 3).

According to another embodiment of the present invention (Example 6), when the combination extract of Magnetization Designation and Magnetization Designed guinea pig, stomach and licorice were administered, the blood pressure was lowered in the high fat diet than in the control fat, (Fig. 4).

According to yet another embodiment of the present invention, the extract of Magnetization Design is administered to a mouse of atherosclerotic disease model deficient in apolipoprotein E gene while taking a high fat diet. In addition, the atorvastatin drug was administered as a normal control (control) and as a normal feed (positive control) (statin) (Example 7-1).

As a result, inhibition of weight gain was observed when the extract designated as the magnetization was administered; Inhibiting liver weight gain; Decreased fat cell size and lipid deposition in liver tissue; Reduced incidence of atherosclerotic lesions; Total cholesterol, low density lipoprotein - cholesterol, triglyceride and glucose levels; Increased AMPK activity; And inhibitory effect on FAS and SREBP-1 protein expression (Examples 7-2 to 7-7).

In the present invention, the term "prevention" means any action which inhibits or delays the lipid-related cardiovascular disease or obesity onset by administration of the pharmaceutical composition according to the present invention, and "treatment" Lipid-related cardiovascular disease, or suspected obesity, and all the behaviors that alleviate or ameliorate the symptoms of the onset.

The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable" of the present invention means that it exhibits properties that are not toxic to the cells or humans exposed to the composition. Such carriers may be used without limitation as long as they are known in the art such as buffers, preservatives, wetting agents, solubilizers, isotonic agents, stabilizers, bases, excipients and lubricants. In addition, the pharmaceutical composition of the present invention can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, oral formulations, external preparations, suppositories, . Furthermore, it can be used in the form of an ointment, a lotion, a spray, a patch, a cream, a powder, a suspension, a gel or a skin external preparation. Examples of carriers, excipients and diluents that can be contained in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used.

Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may contain at least one excipient, for example, at least one excipient in the Magnetized Design Extract or Magnetization Designator, , Starch, calcium carbonate, sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use may include various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. in addition to water and liquid paraffin, which are simple diluents commonly used in suspension, liquid solutions, emulsions and syrups have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of suppositories include macrogol, Tween 61, cacao butter, laurin, glycerogelatin and the like.

The content of the magnetization designation extract, the magnetization designation, the flavor enhancer, and the licorice complex extract contained in the pharmaceutical composition according to an embodiment of the present invention is not particularly limited but may be 0.01 to 100% by weight, More preferably from 1 to 100% by weight.

Meanwhile, the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The term "administering" of the present invention means introducing a predetermined substance into an individual by an appropriate method, and the administration route of the composition can be administered through any conventional route so long as it can reach the target tissue. But are not limited to, intraperitoneal, intravenous, intramuscular, subcutaneous, intradermal, oral, topical, intranasal, intrapulmonary, rectal.

The term "individual" refers to all animals, including rats, mice, livestock, and the like, including humans who have developed or are capable of developing lipid-related cardiovascular disease or obesity. Preferably, it may be a mammal, including a human.

The term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and not causing side effects, and the effective dose level is determined by the patient's sex, Including, but not limited to, medicaments and other medical fields that are used in combination, or in combination with, or in combination with, a pharmaceutically acceptable carrier, excipient, Can be readily determined by those skilled in the art according to known factors. Preferably, the pharmaceutical composition comprising the magnetically-designated extract or the magnetization designation agent, the agent, and the licorice complex extract is administered at a daily dose of 0.0001 to 1000 mg / kg body weight, preferably 0.001 to 500 mg / kg body weight can do. The administration may be such that the recommended dose is administered once a day or divided into several times.

The magnetization designation extract, magnetization designation, guinea pig, lichen and licorice complex extract of the present invention can be safely used because natural herbal medicines are used as raw materials, so that side effects are less than general synthetic compounds.

As another embodiment for achieving the above object, the present invention provides a composition for the prevention or amelioration of lipid-related cardiovascular diseases or obesity comprising as an active ingredient an extract of Magnetization Designation, Magnetization Designation, .

The magnetization designations, donors, warts, licorice extracts, lipid-related cardiovascular diseases, obesity, and prevention are as described above.

The term "improvement" in the present invention means any action in which administration of the composition alters or alleviates the symptoms of lipid-related cardiovascular disease or obesity.

The magnetized design extract of the present invention or the magnetization designation, flavor agent, adhesive, and licorice complex extract not only exhibit the preventive or therapeutic effect of lipid-related cardiovascular disease or obesity, but also have been proved to be safe derived from natural materials, And can be used for the production of a health functional food for preventing or improving obesity.

When used as a food additive, the magnetically designated extract or the magnetization designation, flavor, sweetener, and licorice complex extract may be directly added or used together with other food or food ingredients, and may be appropriately used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment), and may further include a food-acceptable food-aid additive. The content of the magnetically-designated extract or the magnetization designation, flavor, sweetener, licorice complex extract derived from natural materials is not particularly limited in terms of safety, so that the content added to the food additive composition is not particularly limited, Is contained in an amount of 0.001 to 100% by weight, more preferably 0.01 to 80% by weight. In addition, the composition may contain additional ingredients which are commonly used in food compositions and which can improve odor, taste, vision and the like. For example, vitamins A, C, D, E, B1, B2, B6, B12, Niacin, Biotin, Folate, Panthotenic acid and the like. In addition, it may include minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn) and copper (Cu) It may also include amino acids such as lysine, tryptophan, cysteine, valine, and the like. In addition, it is also possible to use antiseptics (such as potassium sorbate, sodium benzoate, salicylic acid, and sodium dehydroacetate), disinfectants (such as bleaching powder and highly bleached white powder, sodium hypochlorite), antioxidants (butylhydroxyanilide (BHA), butylhydroxytoluene BHT), coloring agent (tar color), coloring agent (sodium nitrite, sodium nitrate), bleaching agent (sodium sulfite), seasoning (MSG, sodium glutamate, etc.), sweetener (dicentric acid, cyclamate, saccharin, ), Food additives such as flavorings (vanillin, lactones, etc.), swelling agents (alum, potassium hydrogen D-tartrate), emulsifiers, emulsifiers, thickeners, encapsulating agents, gum bases, foam inhibitors, additives may be added. The additives are selected according to the type of food and used in an appropriate amount.

The food additive composition of the present invention can be used as an additive in the production of a typical food and can be used in the production of a food having an effect of preventing or improving lipid-related cardiovascular diseases or obesity. Functional foods, health functional foods, and the like.

The term "functional food" in the present invention means a food prepared and processed by using a raw material or ingredient having functionality useful to the human body according to Law No. 6727 on health functional foods, and " And function of the nutrient for the purpose of obtaining a beneficial effect in health use such as controlling the nutrient or physiological action.

The term "health functional food" of the present invention refers to a food prepared by processing a specific ingredient as a raw material for the purpose of health assisting or by extracting, concentrating, refining, mixing, or the like a specific ingredient contained in a food raw material, Refers to foods that are designed and processed so as to be capable of sufficiently exhibiting biological control functions such as bio-defense, regulation of biorhythm, prevention and recovery of disease, and the like.

There is no limitation on the kind of food in which the composition of the present invention can be used. Examples of foods that can be added include special nutritional foods such as prepared foods and infant formulas, meat products, fish products, tofu, jelly, noodles such as ramen, noodles, (Such as soy sauce, miso, kochujang, mixed berries, etc.), sauces, confectionery (eg snacks), dairy products (eg fermented milk, cheese), other processed foods, kimchi, pickled foods : Fruits, vegetables, beverages, fermented beverages, etc.), natural seasonings (eg, ramen soup, etc.).

In another aspect of the present invention, the present invention provides a method for treating lipid-related cardiovascular diseases or obesity comprising the step of administering the pharmaceutical composition to a subject in need thereof.

The subject, administration, lipid-related cardiovascular disease, obesity and treatment are as described above.

INDUSTRIAL APPLICABILITY The extract of the magnetism designation or the magnetization designation of the present invention is effective for the prevention or treatment of lipid-related cardiovascular diseases or obesity due to the effects of weight loss, reduction of body fat content, lowering of total cholesterol and blood pressure, Can be used.

In addition, the magnetization designation extract reduced the incidence of atherosclerotic lesions in atherosclerotic model mice; And lipid accumulation inhibitory effect in liver tissue and blood, and thus can be effectively used for preventing or treating arteriosclerosis.

FIG. 1 is a graph showing the results of a comparison between the normal diet group (normal group), the high fat diet (HFD) control group and the high fat diet group of the magnetized design extract or the magnetization designation, The results of the analysis of body weight according to the ages of the group administered with the extract of the magnetized designation, the method of the highland method, the composition of the edible gourd, the mixture of the extract of the licorice and the highland method,
2 is a graph showing the expression of adiponectin mRNA in the control group of the present invention and adipocytes of each experimental group.
FIG. 3 is a graph showing the expression of UCP-2 mRNA in the control group of the present invention and adipocytes of each experimental group.
4 is a graph showing the blood pressure of the control group and each experimental group of the present invention.
FIG. 5 is a graph showing an effect of inhibiting weight gain of a magnetically-designated extract in atherosclerotic model mice.
FIG. 6 is a graph showing the effect of reducing the adipocyte size and lipid deposition of hepatic tissue of the magnetically-designated extract in atherosclerotic model mice.
Fig. 7 is a graph showing the effect of inhibiting liver weight increase of the magnetically-designated extract in the arteriosclerosis model mice.
Fig. 8 is a graph showing the effect of reducing the occurrence of arteriosclerotic lesions of the magnetization-designated extract in the arteriosclerosis model mice (A: photograph showing fat staining in sections of arterial tissue, and B: graph showing atherosclerotic lesion).
Figure 9 shows an increase in AMPK activity of the magnetization-designated extract in atherosclerotic model mice; And suppression of FAS and SREBP-1 protein expression.

Hereinafter, the constitution and effects of the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and the scope of the present invention is not limited by these examples.

Manufacturing example  1. Preparation of extract

The magnetization designation was purchased from Omniherb Co. (Daegu, KOREA), and 10 times of water was added thereto for hot water extraction. The medicinal materials were purchased from Kwangmyong Dang Pharmaceutical (Ulsan, KOREA), and the dry weight of the medicinal materials was mixed with 3, 2, and 2 licorice. The water extracts were prepared by incorporating 1, 2, 3, 4, 5, 6, and 9% of the combined extracts,

Example  1. Production of animal model induced by high fat diet

Male C57bl / 6 mice were imported from Jackson Laboratories, USA (Bar Harbor, Maine, USA), and 10-week old mice with good health status were used for maintenance experiments in SPF (Specific pathogenic free) And drinking water were allowed to eat freely. High fat diets (Rodent diet D12492, Research Diets, New Brunswick, NJ, USA) were purchased from Central Laboratory Animals (Seoul, Korea) and consisted of 20% protein, 20% carbohydrate and 60% fat.

The animals were adapted to the basic diet (AIN-76A diet) for 2 weeks, followed by feeding for 7 weeks with ingestion of high fat diet and medication from 8 weeks of age with body weight of 24 g or more. The experimental group consisted of 6 groups, normal diet (normal diet), normal diet (normal diet), high fat diet (HFD), high fat diet, high fat diet, (15.6 ㎎ / ㎏) treated with high fat diet and 200 ㎎ / ㎏ treated with high fat diet (200 ㎎ / ㎏). All test materials were suspended in physiological saline and administered orally using mouse sonde at the same time every day.

Example  2. Magnetization designation extract or magnetization designation, Anchorage , Weight loss and inhibition of dietary intake of liquorice complex extract

The body weight and dietary intake of the experimental animals were measured by an electronic balance (GP5202, Sartorius, Germany) at the same time once a week. Feed efficiency was calculated by the ratio of body weight gain to feed intake.

(HFD-control group), the body weight decreased from 11 weeks of age when compared to the high fat diet group (HFD-control group), and the combined extract of doenjang, (P <0.05) (Fig. 1), which was significantly lower than that of the sole extract alone.

Group Food intakes (g / day) Body weight gain (g / day) Food efficiency ratio (FER,%) Normal group 3.52     0.161 + - 0.01     4.57 + - 0.30 High-fat diet (HFD-control) 3.14     0.441 0.03 ###    14.06 ± 0.83 ### HFD-Xenical 2.86     0.230 ± 0.01 ***     8.04 0.37 *** HFD - magnetization designation 2.89     0.239 ± 0.01 ***     8.27 ± 0.49 *** HFD-doin, clam, licorice 3.03     0.305 0.03 **    10.06 + - 0.99 * HFD - Designation of magnetization + (Doine, licorice, licorice) 2.99     0.227 ± 0.01 ***     7.59 ± 0.44 ***

###: p <0.001 compared with normal group

*: p <0.05 compared with HFD-control

**: p <0.01 compared with HFD-control group

***: p <0.001 compared with HFD-control group

As shown in Table 1, the body weight gain of the high fat diet group (HFD-control group) was significantly higher than that of the normal fat diet group (normal group), and the high fat diet group HFD-magnetization designation) weight gain was decreased to a significant level (p <0.05). In addition, weight gain was significantly decreased when HFD - magnetization designation + (doenjang, licorice, licorice) was administered with a combination of magnetization designation, doenjang, gill and licorice extract.

The feed efficiency ratio (FER) was significantly lowered in the high fat diet (HFD - magnetization designation) than in the high fat diet, and the combined extracts of doenjang, (HFD-magnetization designation + (pharmacokinetics, licorice, licorice)) (p <0.05) (Table 1).

The results showed that the extracts of Mizuhara designated extract had the effect of suppressing the weight loss and the dietary intake, and the combined extracts of Mizuhana designation, doenjang, mugwort and licorice showed a remarkable effect on the weight loss and the suppression of the dietary intake I could.

Example  3. Specified magnetization extract or magnetization designation, Anchorage , Reducing the Weight Loss of Body Fat of Licorice Complex Extract

As shown in the following Table 2, in the case of the high fat diet (HFD-control group), the subcutaneous fat around the epididymis and the fat around the epididymal fat Tissue, and liver tissues. The weight of subcutaneous, visceral adipose tissue, and liver tissue was significantly decreased in HFD - designated smear - administered group.

In addition, the weight of subcutaneous, visceral adipose tissue, and liver tissue was more effectively reduced in the administration group of the magnetization designation, the administration group of Ganoderma lucidum and licorice complex (HFD-magnetization designation + Respectively.

Group Tissue weight (g) Subcutaneous fat Visceral fat liver Normal group   0.286 ± 0.077   0.280 + 0.032     1.036 0.068 High-fat diet (HFD-control)   1.916 ± 0.120 ###   3.786 + - 0.273 ###     1.116 + 0.036 HFD-Xenical   1.567 + 0.115 *   2.837 ± 0.116 **     1.009 ± 0.043 * HFD - magnetization designation   1.548 + 0.084 *   3.108 0.304     0.922 + 0.031 *** HFD-doin, clam, licorice   1.318 + - 0.234 **   2.848 ± 0.097 **     0.900 0.037 *** HFD - Designation of magnetization + (Doine, licorice, licorice)   1.267 + 0.081 *   2.640 + 0.084 *     0.836 0.030 ***

###: p <0.001 compared with normal group

*: p <0.05 compared with HFD-control

**: p <0.01 compared with HFD-control group

***: p <0.001 compared with HFD-control group

Example  4. Specified magnetization extract or magnetization designation, Anchorage , Effects of Licorice Complex Extract on Blood Lipids

The blood collected from the mice was left at room temperature for 30 minutes and centrifuged at 3000 rpm for 15 minutes to obtain serum. The contents of glucose (glucose, glucose, total cholesterol, triglyceride, low density lipoprotein (LDL) and high density lipoprotein (HDL) were measured and analyzed in the serum using a blood biochemical analyzer 3).

group
(Group) Glucose (mg / dL) Total cholesterol
(Mg / dL) Triglyceride
(Mg / dL) Low density lipoprotein (LDL)
(Mg / dL) High density lipoprotein (HDL)
(Mg / dL) Normal group 101.4 ± 7.3 158.0 ± 3.2 82.8 ± 19.6 42.2 ± 2.6 66.2 ± 3.9 High-fat diet (HFD-control) 157.2 ± 26.5 214.2 ± 7.2 ### 529.8 ± 31.7 ### 56.4 ± 1.9 ## 68.4 ± 3.7 HFD-Xenical 117.0 + - 11.0 173.8 ± 2.0 ** 483.6 + - 44.8 48.4 ± 2.7 84.3 ± 1.5 ** HFD - magnetization designation 93.4 ± 11.2 180.6 ± 7.1 * 454.0 + - 53.8 38.6 ± 2.5 *** 79.2 ± 2.1 * HFD-doin, clam, licorice 93.5 ± 11.8 176.8 ± 5.8 ** 477.0 + - 46.3 36.8 ± 1.5 *** 80.6 ± 2.5 * HFD - Designation of magnetization + (Doine, licorice, licorice) 88.4 8.3 * 171.8 ± 7.6 ** 330.3 ± 11.2 ** 35.4 ± 2.1 *** 78.3 ± 1.2 *

##: p <0.01 compared with normal group

###: p <0.001 compared with normal group

*: p <0.05 compared with HFD-control

**: p <0.01 compared with HFD-control group

***: p <0.001 compared with HFD-control group

As a result of analysis of hematological index, total cholesterol, LDL-cholesterol, triglyceride concentration in the high-fat diet group (HFD-control group) (LDL-cholesterol) and HDL-cholesterol (low-density lipoprotein-cholesterol) were decreased in the control group, (P < 0.05).

In addition, the concentration of glucose, total cholesterol, triglyceride, and LDL-cholesterol in blood was significantly (p <0.05) significantly higher HDL-cholesterol (HDL-cholesterol) concentration was increased (p <0.05).

Example  5. Magnetization Designation Extract or magnetization designation, Anchorage , In the adipose tissue of licorice complex extract Adiponectin ) And UCP -2( Mitochondrial uncoupling  protein-2) gene expression increase effect

The results of real time PCR analysis using visceral adipose tissue of high - fat diet - induced mouse showed that high - fat diet, mixed ginger and licorice extract (HFD - (Adiponectin) mRNA expression was significantly increased in the high-fat diet, and when the high-fat diet method was applied to the combined extracts of the hypothalamus, donor, stomach and licorice (HFD-magnetization designation + Adiponectin mRNA expression was increased (Fig. 2).

The expression of UCP-2 mRNA was increased in the high-fat diet extract (HFD-designated magnetization) or in the case of mixed extracts (HFD-dozen, licorice, licorice) , And UCP-2 mRNA expression was significantly increased (FIG. 3) in the case of administration of a complex extract of licorice (HFD-magnetization designation + (doenjang, licorice, licorice)).

Example  6. Magnetization Designated extract or magnetization designation, Anchorage , Reduction effect of blood pressure of licorice complex extract

Blood pressure was measured using a CODA non-invasive blood pressure system (Kent Scientific Co., Torrington, CT, USA) at the tail of the mouse. Blood pressure was measured 4 times and the systolic blood pressure and diastolic blood pressure And the mean blood pressure (mmHg) (Fig. 4). (HFD-magnetization designation + (doenjang, licorice, licorice)) were administered to the control group (HFD-control group) And decreased blood pressure.

Example  7. Atherosclerosis inhibitory effect of extract

Example  7-1. Production of an animal model of high-fat-induced atherosclerosis

     6-week-old mice deficient in the apolipoprotein E (ApoE) gene as a model of atherosclerotic disease of experimental animals were supplied from Jackson Laboratory (Bar Harbor, Maine, USA) 76A diet) and water were freely supplied. After the purification, high fat diets (Western diet, Research diets, New Brunswick, NJ) were purchased from Central Laboratory Animals (Seoul, Korea) and consist of 45% fat and 0.15% cholesterol.

Animals were fed with high fat diet and medication for 16 weeks from 8 weeks of age. The experimental group consisted of four control groups (Control), which were fed normal diet with normal diet, and high fat diet (HFD), which received saline solution while consuming high fat diets, and high fat diet (100 mg / kg) and a positive control group (statin, 10 mg / kg) receiving atovastatin while consuming high fat diets. All test materials were suspended in physiological saline and orally administered at the same time on a daily basis using a mouse mouse.

Example  7-2. Suppression of weight gain of designated extract

The weight of the experimental animals was analyzed by measuring the electronic scales once a week at the same time. In the high fat diet group, v. Mandshurica extract significantly inhibited body weight gain from 3 weeks compared to the high fat diet group (HFD), and the body weight gain was consistently suppressed more than the positive control group, atorvastatin treatment (P < 0.05) (Fig. 5).

Example  7-3. Suppression of hepatic weight gain of extract

For 16 weeks, mice treated with Magnetized Design Extract were autopsied and liver tissues were extracted and weighed. As a result, the liver weight of HFD was increased compared to the control group, but the weight of the liver tissue was higher than that of the control group (V. mandshurica extract) (P < 0.05) (Fig. 6). This suggests that the extracts of Magnetization Suppresses the increase of liver weight.

Example  7-4. Suppression of lipid deposition in hepatic tissues

Sixteen - week - old mice were sacrificed and the liver tissues were harvested and fixed to give 6 ㎛ - thick sections. Hematoxylin and eosin staining and lipid - specific staining were performed for 16 weeks. The presence of lipid deposits in liver tissue was observed using an oil red O staining method. As a result, lipid deposition in the liver tissue of the mice fed the high-fat diet was progressed compared with that in the normal group, and fat cell size and lipid deposition were reduced in the liver tissue of the medicated group treated with the V. mandshurica extract (P &lt; 0.05) (Fig. 7).

Example  7-5. Inhibition of atherosclerotic lesions of designated extracts

For 16 weeks, mice with the high-fat diet and extracts of Mizuhara designated extracts were autopsied and arterial tissues were extracted and fixed with rapid cooling to prepare 6 μm-thick sections to be stained with oil red O staining And atherosclerotic lesions in the blood vessels were observed. As a result, lipid deposition in the arterial blood vessels was progressed in the mice fed the high fat diet, compared with the normal group, and in the medicated group treated with the V. mandshurica extract, (P < 0.05) (Fig. 8). These results indicate that the magnetically labeled extract has the effect of reducing the incidence of atherosclerotic lesions.

Example  7-6. Blood lipid improvement effect of extracts

     The blood collected from the mice was left at room temperature for 30 minutes and centrifuged at 3000 rpm for 15 minutes to obtain serum. The contents of glucose (glucose, glucose, total cholesterol, triglyceride, low density lipoprotein (LDL) and high density lipoprotein (HDL) were measured and analyzed in the serum using a blood biochemical analyzer 4).

group
(Group) Glucose (mg / dL) Total cholesterol
(mg / dL) Triglyceride
(mg / dL) Low density lipoprotein (LDL)
(mg / dL) High density lipoprotein (HDL)
(mg / dL) Normal group
(Control) 160.43 ±
7.59 462.29 + - 25.80 56.86 + - 6.40 60.00 ± 2.26 17.00 + 2.06 It's a highland system.
(HFD) 402.00
26.55 ###  1381.57 ± 58.18 ### 178.00 ± 17.49 ### 377.86 ± 17.73 ## 9.00 ± 1.15 ## Magnetization designation
Extract (V. mandshurica) 114.67 ±
19.17 ***  864.17 ± 42.74 *** 68.17 ± 11.90 *** 227.67 ± 24.38 *** 11.67 + 1.43 Positive control group
(statin) 275.67 ±
20.12 ***  1184.00 ± 62.00 * 77.33 + - 7.50 *** 262.00 ± 21.14 *** 14.33 ± 1.56 **

##: p <0.01 compared with normal group

###: p <0.001 compared with normal group

*: p <0.05 Comparison with high-fat diet group

**: p <0.01 compared with high-fat diet group

***: p <0.001 Comparison with high-fat diet group

As a result of analysis of hematological index, total cholesterol, low-density lipoprotein-cholesterol, triglyceride, glucose (Glucose), and glucose (high glucose) ), And the concentration of high-density lipoprotein-cholesterol (HDL-cholesterol) decreased. Total cholesterol, LDL-cholesterol, Triglyceride, and Glucose concentrations were decreased when the extracts were administered (p <0.05). From these results, it was confirmed that the extract of Namhae designated to inhibit arteriosclerosis by improving lipid.

Example  7-7. Inhibitory Effect of Fatty Acid-Induced Factor Extract on Hepatic Tissue Synthesis Factors

AMP-activated protein kinase (AMPK), which plays a major role in glucose and lipid metabolism, and expression levels of lipogenic factors were measured by immunohistochemical staining. As a result, the mice fed high-fat diet showed decreased AMPK activity, increased FAS (Fatty acid synthase) and SREBP-1 (Sterol regulatory element-binding protein) mandshurica) inhibited the expression of FAS and SREBP-1 as well as AMPK activity in liver tissues and inhibited arteriosclerosis (FIG. 9).

From the above description, it will be understood by those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. In this regard, it should be understood that the above-described embodiments are to be considered in all respects as illustrative and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention without departing from the scope of the present invention as defined by the appended claims.

Claims (14)

A pharmaceutical composition for prevention or treatment of atherosclerosis or obesity comprising a magnetized design extract, or a combination extract of a magnetization designator, a donor, an agate, and licorice,
Wherein said composition is not due to lipase inhibition and is to prevent or treat obesity by inhibiting or reducing the increase in body weight, body fat or blood triglyceride.
The method according to claim 1,
Wherein the extract is obtained by extracting with a solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, ethyl acetate, acetone, hexane, dichloromethane and a mixed solvent thereof.
The method according to claim 1,
Wherein the extract is obtained by extracting with water as a solvent.
The method according to claim 1,
Wherein the extract is a hot-water extract.
The method according to claim 1,
Wherein the complex extract is extracted by mixing a magnetization designation, an isotope, an adhesive, and a licorice mixture in a weight ratio of 1: 1 to 1: 5.
6. The method of claim 5,
Wherein the complex extract is extracted by mixing a magnetization designation, an isotope, an adhesive, and a licorice mixture in a weight ratio of 1: 3.
The method according to claim 1,
The extract inhibits the body weight gain and body fat increase due to high fat diet (HFD), lowers the blood triglyceride, total cholesterol, LDL-cholesterol, and high density Wherein the composition improves obesity symptoms by increasing HDL-cholesterol.
delete A composition for food additive for improving atherosclerosis or obesity comprising a magnetized design extract or a magnetized designation,
Wherein the composition is not due to lipase inhibition but improves obesity by inhibiting or reducing the increase in body weight, body fat or blood triglyceride.
10. The method of claim 9,
Wherein the extract is obtained by extracting with a solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, ethyl acetate, acetone, hexane, dichloromethane and a mixed solvent thereof.
10. The method of claim 9,
Wherein the extract is a hot-water extract.
10. The method of claim 9,
Wherein the complex extract is extracted by mixing a magnetization designation, an isotope, an adhesive, and a licorice mixture in a weight ratio of 1: 1 to 1: 5.
13. The method of claim 12,
Wherein the complex extract is extracted by mixing a magnetization designation, an isotope, an adhesive, and a licorice mixture in a weight ratio of 1: 3.
A functional food comprising the composition for food addition according to claim 9.

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