WO2017213437A1 - Composition comprising sicyos angulatus extract or fraction thereof as effective ingredient for preventing or treating metabolic disease - Google Patents

Abstract

The present invention relates to a composition comprising a Sicyos angulatus extract or a fraction thereof as an effective ingredient for preventing, relieving, or treating a metabolic disease, and a method for preventing or treating a metabolic disease, comprising a step of administering the composition into a subject suspected of having a metabolic disease.

Description

A composition for the prevention or treatment of metabolic diseases comprising the extract of spiny gourd or fractions thereof as an active ingredient

The present invention comprises a composition for the prevention, improvement or treatment of metabolic diseases, including the extract of Sicyos angulatus or fractions thereof as an active ingredient, and administering the composition to a subject suspected of metabolic diseases, the prevention of metabolic diseases Or to a method of treatment.

In modern society, the obesity population is rapidly increasing due to the convenient living environment, rapid food intake, and the reduction of physical activity due to the increase of processed food and eating out, and accordingly, dyslipidemia and hypertension, hyperglycemia, diabetes, artery Metabolic diseases such as sclerosis, myocardial infarction and dyslipidemia-related diseases such as stroke are increasing.

Obesity is widely known to cause chronic diseases such as fatty liver, high blood pressure, high blood sugar, diabetes, and cardiovascular diseases. 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. Appeared. 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 patients (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. The domestic and overseas anti-obesity drugs are called Zenical, which is based on orlistat, which is approved by the US FDA. In the case of Zenical, which inhibits lipase action, gastrointestinal system such as fatty stool, gas production, and fat-soluble vitamin absorption absorption There are side effects.

Dyslipidemia is a condition in which high levels of total cholesterol, triglycerides, LDL-cholesterol or low HDL-cholesterol levels are found in the blood. In general, LDL-cholesterol is known to be bad cholesterol because it has a property to be deposited on the blood vessel wall, on the contrary, HDL-cholesterol is a good cholesterol because it functions to inhibit the deposition of fat components on the blood vessel wall. Therefore, if the lipid components such as LDL-cholesterol or triglyceride in the blood increases, blood flow is not smooth and lipid components adhere to the arterial wall, causing chronic inflammatory reactions and narrowing of the arterial wall. (arteriosclerosis) is caused. In the long run, clots generated from these clots may cause coronary or cerebral blood vessels, causing myocardial infarction, stroke or cerebral infarction (E. Falk et al., Circulation 92, 657-671, 1995). Currently, drugs for treating hypercholesterolemia are used in the statin class of drugs that have an inhibitory activity of 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 toxicity. In addition, when high LDL-cholesterol or hypertriglyceridemia is generally administered fibric acid derivatives (fibric acid derivatives) is often accompanied by digestive disorders may cause side effects such as myopathy.

On the other hand, while research on natural products that can prevent or treat diseases related to obesity, dyslipidemia or dyslipidemia without any side effects while being safe for the human body (Korea Patent No. 0345040), the development of more effective treatments Necessity is emerging.

The present inventors have made diligent efforts to discover natural substances for preventing or treating metabolic diseases such as obesity, dyslipidemia and dyslipidemia-related diseases without side effects. The present invention was completed by confirming that there is an increase inhibitory effect, triglyceride reduction and increase inhibitory effect, HDL-cholesterol increase, hypoglycemia lowering blood glucose and improving glucose tolerance, and inhibiting the formation of arterial wall adhesion.

One object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of metabolic diseases comprising Sicyos angulatus extract or fractions thereof as an active ingredient.

Still another object of the present invention is to provide a food composition for preventing or improving metabolic diseases, including Sicyos angulatus extract or a fraction thereof as an active ingredient.

Another object of the present invention to provide a feed composition for the prevention or improvement of metabolic diseases, including Sicyos angulatus extract or a fraction thereof as an active ingredient.

Another object of the present invention is to provide a method for preventing or treating metabolic disease, comprising administering the composition to a subject suspected of metabolic disease.

It is another object of the present invention to provide a use of Sicyos angulatus extract or fractions thereof for the manufacture of a medicament for the prevention or treatment of metabolic diseases.

The present invention not only reduces the body weight and body fat, but also lowers the triglyceride in the blood, increases HDL-cholesterol, improves blood sugar lowering and glucose tolerance of hyperglycemia, and inhibits the formation of the adhesion of artery walls. It was confirmed that there is an excellent effect in the prevention and treatment of metabolic diseases such as obesity, dyslipidemia or dyslipidemia-related diseases. In addition, the thorn gourd extract or a fraction thereof may be applied to drugs, food compositions and feed compositions for the prevention or improvement of metabolic diseases such as obesity, dyslipidemia or dyslipidemia-related diseases.

1 is a graph showing that the weight gain rate of animals treated with ethyl acetate fraction of spiny gourd extract was significantly decreased in the mouse model induced obesity and dyslipidemia due to high fat diet (Student's t-test, * p < 0.05 vs control).

Figure 2 is a graph showing that the body weight of the animals administered the ethyl acetate fraction of spiny gourd extract significantly decreased in the mouse model induced obesity and dyslipidemia due to high fat diet (Student's t-test, * p <0.05 vs control).

3 is a graph showing that the body fat of the animals administered the ethyl acetate fraction of spiny gourd extract was significantly reduced in the mouse model inducing obesity and dyslipidemia due to high fat diet (Student's t-test, * p <0.05 vs control).

4 is a graph showing that the triglyceride levels in the animals administered with the ethyl acetate fraction of spiny gourd extract were significantly decreased in the mouse model induced obesity and dyslipidemia due to high fat diet (Student's t-test, * p <0.05 vs control).

FIG. 5 is a graph showing a significant increase in blood HDL-cholesterol in animals administered with ethyl acetate fraction of spiny gourd extract in a mouse model induced obesity and dyslipidemia due to high fat diet (Student's t-test, * * p <0.01 vs control).

FIG. 6 is a graph showing a significant decrease in blood glucose of animals treated with ethyl acetate fraction of spiny gourd extract in a mouse model inducing hyperglycemia due to high fat diet (Student's t-test, * p <0.01 vs control).

7 is a graph showing the improvement of glucose tolerance in animals administered with ethyl acetate fraction of spiny gourd extract in a high fat diet-induced hyperglycemia mouse model (A: blood glucose change by measurement time, B: area under curve (AUA, area under curve)) (Student's t-test, * p <0.01 vs control).

FIG. 8 is a photograph and a graph showing that significantly reduced the formation of arterial wall adhesion in the arteries treated with ethyl acetate fraction of spiny gourd extract in a mouse model deficient in apolipoprotein E (ApoE) to induce atherosclerosis. (Student's t-test, ** p <0.01 vs control).

One embodiment of the present invention provides a composition for the prevention or treatment of metabolic diseases comprising Sicyos angulatus extract or a fraction thereof as an active ingredient.

In the present invention, the thorn extract or fractions thereof, the weight loss and increase inhibitory effect, body fat decrease and increase inhibitory effect, triglyceride reduction and increase inhibitory effect, and HDL-cholesterol increase, hyperglycemia lowering blood sugar and improving glucose tolerance effect and arterial wall It has been confirmed that it can be used for the prevention or treatment of metabolic diseases such as obesity, dyslipidemia, or dyslipidemia-related diseases, as it has an inhibitory effect on the formation of liposomes.

In the present invention, the term "Sicyos angulatus" is a perennial vine plant belonging to the fruit family, herbicidal activity and antimicrobial activity is known, such as thorn gourd extract is related to obesity, dyslipidemia or dyslipidemia It has not been disclosed that there is a prophylactic or therapeutic effect of metabolic diseases such as diseases, and was first identified by the present inventors. In the present invention, the spiny gourd may be purchased commercially, or may be used collected or grown in nature.

In the present invention, the term "extract" refers to an extract, such as an extract obtained by an extraction process of spiny gourd, a diluent or concentrate of the extract, a dried product obtained by drying the extract, a modifier or purified product of the extract, or a mixture thereof. And extracts of all formulations that can be formed using extracts.

In the present invention, the thorn gourd extract is pulverized after washing and drying the thorn gourd; And extracting the pulverized spiny gourd with a solvent selected from the group consisting of water, C1 to C6 alcohols, and mixed solvents thereof. The thorn extract may be specifically extracted with methanol, ethanol, propanol, butanol, pentanol or hexanol, more specifically may be extracted with ethanol, but is not limited thereto.

The extraction method is not particularly limited and may be extracted at room temperature or warmed under conditions where the active ingredient is not destroyed or minimized. More specifically, the method for obtaining a thorn gourd extract in the present invention is as follows. The dried spiny foil is a polar solvent of C1 to C6 alcohols such as water, methanol, ethanol, propanol, butanol, pentanol and hexanol in volumes of about 2 to 20 times, specifically about 3 to 5 times the weight, or A mixed solvent having a mixing ratio of about 1: 0.1 to 1:10 can be used as the elution solvent, but is not limited thereto. The extraction temperature may be 1 to 100, specifically 25, the extraction period may be about 1 hour to 10 days, specifically 2 to 50 hours, the extraction method is shaking extraction, hot water extraction, cold extraction, reflux cooling Extraction, ultrasonic extraction, or a combination thereof, but is not limited thereto. In a specific embodiment of the present invention, the process of soaking with 70% ethanol for 2 hours and then standing at room temperature for 1 hour was repeated three times a day, followed by extraction, filtration and concentration, and freeze-dried to obtain the spinach extract.

The prickly pear extract can be extracted from natural, hybrid, mutant plants, and can be extracted from plant tissue culture.

The term "fraction" in the present invention means the result obtained by performing the fractionation to separate a specific component or a specific component group from a mixture comprising various various components.

In the present invention, the fractionation method for obtaining the fraction is not particularly limited, and may be performed according to a method commonly used in the art. As a non-limiting example of the fractionation method, an extract obtained by extracting spiny gourd may be treated with a predetermined solvent to obtain a fraction from the extract.

The kind of the fractionation solvent used to obtain the fraction in the present invention is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the fractionation solvents include polar solvents such as water and alcohols; And nonpolar solvents such as hexane, ethylacetate, acetone, and chloroform. These may be used alone or in combination of two or more thereof. In addition, it is also possible to use a method of extracting the thorn foil to pass through the ion exchange resin to fractionate the extract, the ion exchange resin used to fractionate the thorn foil in the present invention in more detail as an aromatic unsubstituted resin ( Diaion HP-20, SP825, AXT204, XAD1600T, MN200). In a specific embodiment of the present invention, the barley extract was extracted with 70% ethanol and concentrated to obtain a fraction obtained by solvent fractionation with ethyl acetate.

In the present invention, the term "prevention" means any action that inhibits or delays the development of metabolic diseases such as obesity, dyslipidemia or dyslipidemia related diseases by administration of the thorn gourd extract, fractions thereof, or the composition according to the present invention. Say. The term treatment in the present invention refers to any action in which the symptoms of the disease are improved or beneficially altered by administration of the thorn extract, fractions thereof or the composition according to the present invention.

As used herein, the term “metabolic disease” refers to a disease caused by metabolic disorders in vivo, and may specifically include obesity, dyslipidemia or dyslipidemia related diseases, but is not limited thereto. Does not. In the present invention it was confirmed that the thorn gourd extract is effective in the prevention or treatment of metabolic diseases.

In the present invention, the term "obesity" refers to a state in which body fat is excessively accumulated. Criteria for obesity may be described as obesity if the body fat is 25% or more of body weight, women more than 30-35%, body mass general measurement methods as is shown by the weight (kg) / height (m) ² index (BMI; Body Mass Index) is widely used. Western body mass index of over 30kg / m ² is defined as obesity, 25 ~ 30kg / m ² is defined as overweight, in the case of Asians more than 28kg / m ² , obesity, 23 ~ 28kg / m ² Is overweight. In addition, obesity may be defined on the basis of a waist to hip ratio (WHR) or abdominal fat mass, and the present invention includes all cases of obesity defined by a general standard other than the above-mentioned criteria. do. In the present invention, using the thorn gourd extract confirmed the weight and body fat reduction and increase inhibitory effect.

In a specific embodiment of the present invention, to investigate the effect of the thorn gourd extract and fractions on the inhibition of body absorption of obesity and triglycerides, orally administered each of the thorn gourd extract and fractions for 14 hours, 30 minutes After ingesting corn oil (corn oil) and then 2 hours after the mouse blood was collected to measure the concentration of triglycerides in the blood, as a result, the administration of thorn extract (SA extract) and fraction (SA fraction) compared to the control group It was found to be significantly reduced in the group (Table 1). In addition, it was found that the administration of the thorn gourd extract (ethyl acetate fraction of the thorn gourd extract) is more effective than the thorn gourd extract, so that the ethyl acetate fraction of the thorn gourd extract was administered in the remaining experiments. In addition, the weight change according to the administration of ethyl acetate fraction of the thorn gourd extract was measured in the mice fed the high-fat diet for 8 weeks, and as a result, the weight gain rate was decreased in the group administered the ethyl acetate fraction of the thorn gourd extract compared to the control group. 1 and 2, and after 8 weeks from the start of the administration, the mouse was subjected to autopsy to measure the weight of the subcutaneous fat, the body fat was significantly reduced in the group administered the ethyl acetate fraction of thorn gourd extract compared to the control group It was confirmed that there was (Fig. 3).

As used herein, the term "dyslipidemia" refers to a state in which lipid components such as triglycerides, LDL cholesterol, phospholipids and free fatty acids are increased or HDL-cholesterol is decreased in blood. The dyslipidemias include hyperlipidemia, high LDL-cholesterolemia, low HDL-cholesterolemia and hypertriglyceridemia. In the present invention, the ethyl acetate fraction of the spiny gourd extract was used to confirm the effect of inhibiting triglyceride in blood and increasing the blood HDL-cholesterol.

As used herein, the term "dyslipidemia related disease" refers to various diseases caused by dyslipidemia, and the diseases that can be treated or prevented by the pharmaceutical composition of the present invention include, but are not limited to, arteriosclerosis, myocardial infarction. , Stroke, cerebral infarction, hypertension, hyperglycemia, diabetes, tangier disease, ischemic heart disease and ischemic brain disease.

In a specific embodiment of the present invention, blood triglyceride and HDL-cholesterol levels were measured in accordance with the administration of ethyl acetate fraction of spiny gourd extract in a mouse model inducing obesity and dyslipidemia due to high fat diet. In comparison, the triglyceride fraction was significantly decreased in blood triglyceride (FIG. 4), and significantly increased in HDL-cholesterol (FIG. 5). In addition, in the mouse model inducing hyperglycemia due to high fat diet intake, blood glucose was measured according to the administration of ethyl acetate fraction of the thorn gourd extract. As a result, the blood glucose was significantly reduced in the group administered the thorn gourd fraction compared to the control group (FIG. 6). ), It was confirmed that glucose tolerance was significantly suppressed by improving glucose tolerance (FIG. 7). In addition, in the apolipoprotein E (ApoE) deficient mouse model, the rate of formation of the adherence of arterial wall in the artery wall according to the administration of the ethyl acetate fraction of the thorn extract was measured. This was found to be significantly reduced (FIG. 8).

Through the above results, it was confirmed that the composition comprising the thorn gourd extract of the present invention or a fraction thereof has an excellent effect for the prevention or treatment of metabolic diseases such as obesity, dyslipidemia or dyslipidemia-related diseases.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier.

The pharmaceutical compositions of the invention may be prepared in pharmaceutical formulations using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. In the preparation of the formulation, it is preferred that the active ingredient is mixed or diluted with the carrier or enclosed in a carrier in the form of a container.

Accordingly, the pharmaceutical compositions of the present invention can be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral formulations, external preparations, suppositories, and sterile injectable solutions according to conventional methods. And may further comprise suitable carriers, excipients and diluents conventionally used in the preparation of the composition.

For example, carriers that may be included in the pharmaceutical compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.

Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which include at least one excipient such as starch, calcium carbonate, sucrose in the compound. Or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.

Oral liquid preparations include suspensions, solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. have.

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

As used herein, the term "administration" means introducing the pharmaceutical composition of the present invention to a patient in any suitable manner.

The mode of administration of the pharmaceutical composition according to the present invention is not particularly limited, and may be in accordance with methods commonly used in the art. The mode of administration is not limited as long as it can reach the target tissue, but may be intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, intranasal administration. The pharmaceutical compositions according to the invention may be prepared in various formulations depending on the desired mode of administration.

The pharmaceutical composition of the present invention may be administered in a pharmaceutically effective amount.

The "pharmaceutically effective amount" means an amount sufficient to treat the disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type of subject and its severity, age, sex, type of virus infected, drug Activity, sensitivity to drug, time of administration, route of administration and rate of release, duration of treatment, factors including concurrent use of drugs, and other factors well known in the medical arts.

A typical daily dosage of a pharmaceutical composition according to the invention may be administered such that the spiny gourd extract or fractions thereof is administered at 10 to 1,000 mg / kg, specifically 10 to 600 mg / kg, divided once or in several portions. May be administered.

According to a specific embodiment of the present invention, the ethyl acetate fraction of spiny gourd extract is administered orally once a day at a concentration of 300 mg / kg, thereby effectively treating a mouse model of obesity and dyslipidemia induced by high fat diet. It was confirmed.

The composition of the present invention may be administered daily or intermittently, and the number of administrations per day may be administered once or divided into two or three times. In addition, the composition of the present invention can be used alone or in combination with other drug treatment for the prevention or treatment of obesity, dyslipidemia or dyslipidemia related 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.

Another aspect of the present invention provides a method for preventing or treating a metabolic disease, comprising administering the pharmaceutical composition to a subject suspected of metabolic disease. Specifically, the metabolic disease may include obesity, dyslipidemia or dyslipidemia related diseases, but is not limited thereto. In one embodiment, the method provides a method for preventing or treating a metabolic disease, comprising administering the composition to a subject suspected of metabolic disease.

Prickly pear extracts, fractions, metabolic diseases are as described above.

As used herein, the term "individual" means all animals, including humans, who have or are likely to develop metabolic diseases. The animal may be a mammal such as, but not limited to, a human, a cow, a horse, a sheep, a pig, a goat, a camel, a antelope, a dog, a cat, and the like, which require treatment of similar symptoms.

The method of preventing or treating the present invention specifically includes administering the composition in a pharmaceutically effective amount to a subject having or at risk of developing a metabolic disease such as obesity, dyslipidemia or dyslipidemia related diseases. It may include.

Yet another aspect of the present invention provides a food composition for preventing or improving metabolic diseases, including thorn gourd extract or a fraction thereof as an active ingredient. Specifically, the metabolic disease may include obesity, dyslipidemia or dyslipidemia related diseases, but is not limited thereto.

Prickly pear extracts, fractions, metabolic diseases are as described above.

Since the food composition of the present invention can be consumed on a daily basis, it is very useful because it can be expected to prevent or improve metabolic diseases such as obesity, dyslipidemia or dyslipidemia-related diseases.

As used herein, the term "improvement" means any action that at least reduces the parameters associated with a condition, e.g., the degree of symptoms, that are treated by administration of a composition comprising a spiny gourd extract or fractions thereof.

The food composition for preventing or improving metabolic diseases of the present invention includes the form of pills, powders, granules, acupuncture, tablets, capsules or liquids, and the like to which the composition of the present invention can be added, for example, Various foods, for example, drinks, chewing gum, tea, vitamin complexes, dietary supplements and the like.

There is no particular limitation on the other ingredients except for containing the thorn gourd extract or a fraction thereof as an essential ingredient that may be included in the food composition of the present invention, and various herbal extracts, food supplement additives or natural carbohydrates, and the like, as in general foods, are additional ingredients. It may contain as.

In addition, the food supplement additives include food supplement additives conventional in the art, such as flavoring agents, flavoring agents, coloring agents, fillers, stabilizers and the like.

Examples of such natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. In addition to those mentioned above, natural flavoring agents (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used as flavoring agents.

In addition to the above, the food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. Others may contain pulp for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components can be used independently or in combination.

The health supplement food in the present invention includes a health functional food and health food.

The functional food (functional food) is the same term as a food for special health use (Food for special health use, FoSHU), in addition to the nutritional supply, the processed food, so that the bioregulatory function appears efficiently, high medical effect Means food. Here, the term "functionality" means obtaining useful effects for health purposes such as nutrient control or physiological action on the structure and function of the human body. The food of the present invention may be prepared by a method commonly used in the art, and the preparation may be performed by adding raw materials and ingredients commonly added in the art. In addition, the formulation of the food may also be prepared without limitation as long as the formulation is recognized as a food. Food composition of the present invention can be prepared in various forms of formulation, unlike the general medicine has the advantage that there is no side effect that can occur when taking a long-term use of the drug as a food raw material, excellent portability, Food can be taken as an adjuvant for enhancing the effect of preventing or improving metabolic diseases such as obesity, dyslipidemia or dyslipidemia related diseases.

Another aspect of the present invention, the present invention provides a feed composition for the prevention or improvement of metabolic diseases comprising a thorn gourd extract or a fraction thereof as an active ingredient. Specifically, the metabolic disease may include obesity, dyslipidemia or dyslipidemia related diseases, but is not limited thereto.

Spiny bark extract, fractions, metabolic diseases, prevention and improvement are as described above.

The feed composition may include a feed additive. The feed additive of the present invention corresponds to a feed supplement in the Feed Control Act.

As used herein, the term "feed" may refer to any natural or artificial diet, one meal, or the like, or a component of the one meal, for the animal to eat, ingest, and digest.

The kind of the feed is not particularly limited, and may be used a feed commonly used in the art. Non-limiting examples of the feed include, but are not limited to, vegetable feeds such as cereals, fruits, food processing by-products, algae, fibres, pharmaceutical by-products, oils, starches, gourds or grain by-products; And animal feeds such as proteins, minerals, fats and oils, minerals, fats and oils, single cell proteins, zooplankton or foods. These may be used alone or in combination of two or more thereof.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only intended to illustrate the invention and are not to be construed as limiting the scope of the invention by these examples.

Example  One: Barbed  Extracts and Its Fraction  Produce

After drying the thorn (1,500g) and pulverized, 70% ethanol (10L) was added as a solvent, and the extraction solution was repeated three times a day after sonication at room temperature for 2 hours and left at room temperature for 1 hour. The solution was filtered, concentrated under reduced pressure, the sample was frozen in a deep freezer and dried using a lyophilizer. In addition, in order to prepare a fraction of thorn foil, after obtaining the thorn foil soft extract (165g) by the same method as described above, added 5-10 times the amount of purified water, dissolved and suspended, and then normal hexane (n- hexane), ethyl acetate (EtOAc), butanol (BuOH) was used stepwise to fractionate the active material. Thereafter, the obtained ethyl acetate solvent was concentrated under a reduced pressure concentrator, followed by further freezing the sample in a deep freezer and drying using a freeze dryer (dry extract (20.55 g)). Thus prepared thorn gourd extract and its ethyl acetate fraction was dissolved in 0.5% CMC (carboxy methylcellulose) solution for the experiment of mice fed high fat diet and mice fed corn fat.

Example  2: acute with corn fat intake Triglyceridemia  In induced mouse model Barbed  Extracts and Its Fraction  Changes in Triglyceride Levels in Blood with Administration

After fasting for 14 hours in 9-week-old male C57BL / 6 mice, the thorn gourd extract prepared in Example 1 and its ethyl acetate fraction were administered once daily at a concentration of 300 mg / kg, 30 minutes later, Corn oil (Corn oil, Sigma, USA), which is mostly triglycerides, was orally administered to each group of mice at a concentration of 9 g / kg. After 2 hours, blood was collected from a heparin-treated capillary tube from the retro-orbital sinus of each animal, and centrifuged at 10,000 rpm for 10 minutes. The upper plasma was obtained and analyzed directly using an automatic blood analyzer (Hitachi 7150, Japan).

As a result, the triglyceride and the level of blood in the control group were 223 ± 6mg / dl, whereas the group treated with spinach extract (SA extract) and its ethyl acetate fraction (SA fraction) were 197 ± 13mg / dl and 190 ±, respectively. 2 mg / dl was found to be significantly reduced (Student's t-test, * p <0.05) (Table 1). From these results, it was confirmed that the thorn gourd extract and fractions thereof have an effect of preventing hypertriglyceridemia or obesity by inhibiting the absorption of lipid components such as triglycerides from the outside through the diet.

division	Triglycerides in the blood (mg / dl)
Control	223 ± 6
SA extract	197 ± 13
SA fraction	190 ± 2

Example  3: high fat Diet  In the mouse model Barbed  Analysis of the effects of administration

Example  3-1: high fat diet ingested mice and Prickly  Oral administration condition

Eight-week-old male C57BL / 6 mice were fed a high-fat diet (Research diets # 12492) containing 60% of dietary fat for eight weeks. Ethyl acetate fraction of spiny gourd extract was orally administered once a day for 8 weeks at a concentration of 300 mg / kg while eating a high fat diet. In addition, the control group was orally administered once daily with 0.5% CMC, a solvent in which the spiny gourd fraction was dissolved while taking the same high fat diet. Feed intake was limited during the experiment and water was free for all animals. The breeding conditions of the animal room were carried out while maintaining in a specific pathogen-free (SPF) environment controlled by the temperature 22 ± 2, humidity 55 ± 10%, and lighting 12 hours cycle contrast.

Example  3-2: high fat Diet  In ingested mouse model Barbed  Weight change with administration

Eighty-week-old male C57BL / 6 mice were fed with ethyl acetate fraction of the spiny gourd extract prepared in Example 1 at a concentration of 300 mg / kg once a day while eating a high fat diet. Measured weekly. As a result, the weight of the mice administered the ethyl acetate fraction of the thorn extract was 27 ± 0.6 g at 2 weeks of administration, compared to 30 ± 0.8 g in the control group, and the weight gain was significantly inhibited. Lasting to 8 weeks, the weight of the control group was 41 ± 0.5g, compared to 35 ± 0.4g in the bakbak group. As a result of the average weight gain, the group administered with the ethyl acetate fraction of the spiny gourd extract was found to have a 20% lower weight gain than the control group (FIGS. 1 and 2). That is, it was found that the thorn gourd extract and its fractions are very excellent in weight loss and weight increase inhibitory effect.

Example  3-3: high fat Diet  In ingested mouse model Barbed  Body fat change with administration

Eighty-week-old male C57BL / 6 mice were administered once daily with ethyl acetate fraction of the spiny gourd extract prepared in Example 1 at a concentration of 300 mg / kg while ingesting a high fat diet. After 8 weeks, an autopsy was performed to separate the subcutaneous fat, inguinal (I) fat, visceral fat, gonadal (G) fat and retroperitoneal fat, retro-peritoneal (R) fat. Analyzed.

As a result, I fat was 66 ± 9%, G fat was 75 ± 11%, and R fat was 81 ± 11% in mice treated with ethyl acetate fraction of thorn extract compared to the control group. (Student's t-test, * p <0.05) (Fig. 3). From these results, it was found that the thorn gourd extract and fractions thereof have a very good effect of reducing body fat and increasing body fat.

Example  3-4: high fat Diet  In ingested mouse model Barbed  Changes in Triglyceride and HDL-Cholesterol Levels in Blood Following Administration

Eighty-week-old male C57BL / 6 mice were fed an ethyl acetate fraction of thorn gourd extract prepared in Example 1 for 8 weeks in a mouse model ingesting a high fat diet and inducing obesity and dyslipidemia. Blood was collected using a capillary tube treated with heparin from a retro-orbital sinus. The collected blood was centrifuged at 10,000 rpm for 10 minutes to obtain plasma in the upper layer, and analyzed directly using an automatic blood analyzer (Hitachi 7150, Japan).

As a result, the blood triglycerides and levels in the control group were 271 ± 63mg / dl, while the ethyl acetate fraction of thorn extract was significantly reduced to 129 ± 11mg / dl (Fig. 4). In the case of HDL-cholesterol, the control group was 85 ± 8 mg / dl, whereas the group treated with ethyl acetate fraction of thorn extract was significantly increased to 132 ± 10 mg / dl (FIG. 5). From these results, it was confirmed that the thorn gourd extract and its fractions lower the triglyceride in the blood and increase the HDL-cholesterol to effectively inhibit and improve dyslipidemia.

Example  3-5: high fat Diet  In ingested mouse model Barbed  Changes in blood sugar levels with administration

Eighty-week-old male C57BL / 6 mice were fed a high fat diet to induce hyperglycemia in a mouse model for 8 weeks, the ethyl acetate fraction of the thorny bark extract prepared in Example 1 at a concentration of 300 mg / kg 1 day 1 Oral administration was performed and blood glucose changes were measured at two week intervals.

As a result, the blood glucose level was significantly decreased in the group administered with ethyl acetate fraction of thorn bark extract from 2 weeks after administration, and at 8 weeks of administration, the control group showed 227 ± 6 mg / dL at the start of administration. The blood sugar level was increased by 16% compared to 196 ± 6 mg / dL, whereas the group treated with ethyl acetate fraction of thorn extract showed 163 ± mg / dL, 21% higher than 206 ± 4 mg / dL at the start of administration. It was confirmed that the degree was significantly reduced (Fig. 6). These results indicate that the administration of spiny gourd maintained the hyperglycemia induced by high-fat diet for 8 weeks at about 37% lower than that of the control group. It was.

Example  3-6: high fat Diet  In ingested mouse model Barbed  According to administration Glucose tolerance  change

In an eight-week-old male C57BL / 6 mouse, a high-fat diet-induced hyperglycemic mouse model induces hyperglycemia. In the experimental group, ethyl acetate fraction of spiny gourd extract was administered once daily at a concentration of 300 mg / kg. At the 6th week of administration, mice in the control and experimental groups were tested for glucose tolerance test. In the glucose tolerance test, all the mice were fasted for 16 hours, intraperitoneally injected with glucose adjusted to a concentration of 2 g / kg, and blood was collected at 0, 30, 60, 90 and 120 minutes to measure blood glucose. The measured blood glucose was shown in a line graph, and the area under the curve of the control group and the experimental group shown in the graph of the blood glucose change line and the X-axis of the graph was calculated and compared.

As a result, 16 hours fasting glucose measured at 0 minutes of administration of glucose showed 91 ± 2.9 mg / dL in the group treated with ethyl acetate fraction of spiny gourd, and the control group showed 122 ± 5.5 mg / dL. The blood sugar level of was significantly lower, and also in the experimental group administered with thorn gourd at all the blood glucose measurement time, such as 30, 60 and 120 minutes after the glucose administration significantly lower than the blood sugar of the control group (Fig. 7A). On the other hand, the area under the curve calculated on the line graph (Comparative results), even in the group administered the ethyl acetate fraction of thorn extract showed that the area under the curve was significantly lower than the control group (Fig. 7 B) . From these results, it was confirmed that the thorn gourd extract exhibits excellent antidiabetic activity by improving glucose tolerance and suppressing blood glucose increase.

Example  4: Apolipoprotein  E ( ApoE Deficiency induced by atherosclerosis in mouse model Artery wall Policy  change

8 week old male ApoE deficient mice were ingested atherosclerosis diet (Dyets # 102571, USA) containing 1.25% cholesterol for 8 weeks. Mice were divided into two groups, and both groups were fed orally with an atherosclerosis diet, and the oral solution was treated with 0.5% CMC solution in the control group and 0.5% CMC suspension in ethyl acetate fraction of 500mg / kg once daily. Administered directly. During the experiment, feed intake and water were freely available to all animals, and the breeding conditions of the animal room were maintained in a SPF environment controlled by a temperature of 22 ± 2 ° C, 55 ± 10% humidity, and a 12 hour light cycle. The experiment was performed. Eight weeks later, the experiment was terminated and necropsy was performed to separate the arterial site from the aortic arch start to the abdominal aortic distal end, followed by fixation with 10% neutral formalin for at least 24 hours, after which fat was deposited. Oil-red O staining was performed to color the area (atherosclerosis) in red color and analyzed by visual and image analysis program.

As a result of the analysis, the group of barbed gourd fractions administered at a concentration of 500 mg / kg showed that the degree of red coloration in the arterial wall was reduced visually. In addition, as a result of analyzing the ratio of the area stained red by oil-red O to the total area of the artery wall through the image analysis program, the control group showed 32.3 ± 2.7%, 18.5 ± 4.0%. In terms of the control group again, the spinach fraction administered group was found to be very low as 57 ± 4% of the adherence ratio of the control group (100 ± 3%) of the lichen planar (atherosclerosis) rate of the inner artery wall. (Student's t-test, * p <0.01) (FIG. 8).

Through this, it was found that the thorn gourd extract and its fractions can effectively prevent and treat atherosclerosis.

Example  5: statistical analysis

All values are expressed as mean ± standard error (SEM). The significance level was set to 0.01 or 0.05 for significance between the mean values, and statistical methods used for analysis were analyzed by Student's t-test.

Taken together, the thorn extract or fractions thereof have weight loss and increase inhibition effect, body fat reduction and increase inhibition effect, triglyceride reduction and increase inhibition effect, HDL-cholesterol increase, hyperglycemia lowering blood sugar and improving glucose tolerance and artery It was found that there is an inhibitory effect on the formation of the paper fibers in the inner wall. This suggests that the thorn gourd extract of the present invention or a fraction thereof has a very good effect on the prevention, improvement and treatment of metabolic diseases such as obesity, dyslipidemia or dyslipidemia related diseases.

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

Claims (11)

1. Pharmaceutical composition for the prevention or treatment of metabolic diseases, including Sicyos angulatus extract or a fraction thereof as an active ingredient.
2. The method of claim 1,

   The extract is a pharmaceutical composition that is extracted with a solvent selected from the group consisting of water, C1 ~ C6 alcohol and mixed solvents thereof.
3. The method of claim 2,

   Wherein the alcohol solvent is selected from the group consisting of methanol, ethanol, propanol, butanol, pentanol and hexanol.
4. The method of claim 1,

   Wherein the fraction is obtained by fractionating the thorn gourd extract with a solvent selected from the group consisting of water, alcohol, hexane, ethyl acetate, acetone, chloroform and a mixed solvent thereof.
5. The method of claim 1,

   The metabolic disease comprises obesity, dyslipidemia or dyslipidemia related disease, pharmaceutical composition
6. The method of claim 5,

   The dyslipidemia is at least one disease selected from the group consisting of hyperlipidemia, hyper-LDL-cholesterolemia, hypertriglyceridemia and hypo-HDL-cholesterolemia, pharmaceutical composition.
7. The method of claim 5,

   The dyslipidemia is at least one disease selected from the group consisting of hyperlipidemia, hyper-LDL-cholesterolemia, hypertriglyceridemia and hypo-HDL-cholesterolemia, pharmaceutical composition.
8. The method of claim 1,

   The pharmaceutical composition will further comprise a pharmaceutically acceptable carrier.
9. Food composition for the prevention or improvement of metabolic diseases, including Sicyos angulatus extract or fractions thereof as an active ingredient.
10. Feed composition for the prevention or improvement of metabolic diseases, including Sicyos angulatus extract or fractions thereof as an active ingredient.
11. A method of preventing or treating metabolic disease, comprising administering the composition of any one of claims 1 to 8 to a subject suspected of metabolic disease.

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