KR101814257B1 - Composition for Anti-obesity Using an Extract of Arisaema ringens - Google Patents

Abstract

The present invention discloses an anti-obesity composition using a large artificial extract having the activity of inhibiting the differentiation of precursor adipocytes into adipocytes.

Description

TECHNICAL FIELD The present invention relates to a composition for an anti-obesity using an extract of Araliaceae,

The present invention is based on the invention of the Arisaema ringens extract of the present invention.

Due to changes in Westernized eating habits and lifestyle habits, the population of obesity is rapidly increasing. According to the National Health and Nutrition Examination Survey (NHRC) in 2013, the prevalence of obesity (age 19 and over, standardization) was 31.8%, and 3 out of 10 Korean adults were obese (Knhanes, Health Behavior and Chronic Disease Statistics, 2013). The World Health Organization (WHO) has also classified obesity as a disease that is not a symptom or symptom, and it has been reported that by 2015 the global obesity population will increase to 1.5 billion people and become a major health problem (Ann Epidemiol. 2005. 15: 87-97; J Life Sci., 2013. 23: 69-78).

Obesity is caused not by a single cause, but by a combination of various causes such as dietary habits, high calorie diet, lack of exercise due to a busy social environment, endocrine abnormalities, and genetic and environmental influences and changes in eating habits (Am J Clin Nutr 1998: 67: 563S-572S, Nutr Res 1997. 55: 150-156).

Obesity is a phenomenon in which excessive consumption of body fat accumulates in the body, which is caused by an imbalance between energy intake and consumption, which causes excessive metabolism of various metabolic syndrome diseases such as hyperlipidemia, hypertension, diabetes, stroke, arteriosclerosis Increase incidence (Cell 104: 531-543, 2011) and increase the incidence of diseases such as joint disease, respiratory disease and cancer (Endocrinol Metab. 2010. 25 (4): 301-304). In addition, due to the increased interest in appearance and changes in the perception of body shape, it also causes mental illness such as loss of self-confidence and depression.

The energy in the body is stored in the form of triglyceride in the fat cells. When the energy source in the body is exhausted, the stored fat is decomposed into free fatty acid and glycerol and used as an energy source. However, And increases the amount of stored fat in the body, which is a direct cause of obesity.

Fat cells are the cells that accumulate the energy needed by the body. They play an important role in lipid metabolism by synthesizing, storing or decomposing energy in the form of triglycerides when necessary. In order to maintain such energy homeostasis, various transcription factors and various genes and enzymes are involved in induction of adipocyte differentiation, lipogenesis and lipolysis. In the differentiation stage of adipocytes, PPARγ (peroxisome proliferator-activated receptor γ), C / EBP family (CCAAT / enhancer binding proteins; C / EBRα, C / EBRβ and C / EBRδ), ADD1 / SREBP1c (adipocyte determination differentiation factor 1) / (sterol regulatory element binding protein 1c) are induced in different stages of the adipocytes undergoing differentiation, and the expression of various adipocyte-specific genes is regulated through the interaction of the respective factors ( Genes De 2000, 14 (11) 1293-1307) ( Physiol Rev 1998, 78 (3): 783-809; Annu Rev Biochem 2008, 77: 289-312; Genes Dev 1996, 10: 1096-1107). The fatty acid synthase (FAS), acetyl-CoA carboxylase (SCA), stearoyl-CoAdesaturase (SCD), and ACS are the enzymes involved in triglyceride biosynthesis. (acyl-CoA synthetase), and DGAT (diacylglycerol acyltransferase) (Trends Endocrinol. Metab., 23, 56-64, 2011; Biochem. Biophys. Res. Commun., 420, 805-810. The triglycerides synthesized by the action of these enzymes are used as an energy source. Lipid degradation is controlled by catecholamines and insulin depending on nutritional status. The enzymes involved in lipolysis include ATGL (adipose triglyceride lipase), HSL (hormone sensitive lipase) and MGL (monoacyl glycerol lipase). When the enzyme triggers hydrolysis of one molecule of triglyceride, (Trends Endocrinol. Metab., 23, 56-64, 2011; Biochem. Biophys. Res. Commun., 420, 805-810, 2012). Fatty acids produced by hydrolysis are oxidized in mitochondria, consumed as energy, or esterified and synthesized as triglycerides and stored in cells.

3T3-L1, a lipogenic precursor cell, is the most widely used model currently used to study adipocytes for molecular biology, and is widely used for searching for anti-obesity material (Cell 92: 437-440, 1998; Crit Rev Biochem Mol Biol 40: 229-242, 2005).

The mechanism of pharmacological action for the development of obesity therapy has been divided into three categories: the mechanism of interfering with the absorption of fat in the small intestine, the mechanism of suppressing the appetite and the excess energy entering the body into fat And promote the metabolism of energy in the body and release it into heat.

Xenical ™ (Roche Pharmaceuticals, Switzerland) is a representative treatment for obesity using a pharmacological mechanism to inhibit fat digestion and absorption, and Reductil ™ (Abbott Laboratories, Inc.) is a representative treatment for obesity using a pharmacological mechanism to suppress appetite. , USA). Exorise (Exorise ™, Acopama, France) is a representative treatment for obesity using a pharmacological mechanism for promoting energy metabolism in the body.

Most of the currently used treatments for obesity have adverse effects such as abdominal pain, nausea, vomiting, headache, insomnia, gastrointestinal disorders, and elevated blood pressure. Reducetil (sibutramine) has already been withdrawn from the market in 2010 due to controversy over cardiovascular side effects. Therefore, efforts are being actively made to develop new drugs from natural products with relatively few side effects (J Korean Med Obes Res 2013, 13 (2): 74-75).

It is a perennial herb that is distributed in Korea, Japan, China, Taiwan, etc., and the bulb has been used as a medicinal material in geomorphic, giant wind, gyeonggyeong (Jeong Yeon-ok, etc., wild flower book, 2010; ).

The present invention discloses an anti-obesity use of a large artificial extract based on lipid precursor differentiation inhibitory activity and the like of lipid precursor cells.

It is an object of the present invention to provide a composition for anti-obesity using a large artificial extract.

Other and further objects of the present invention will be described below.

The present invention inhibits the differentiation of 3T3-L1 mouse precursor adipocytes into adipocytes in a concentration-dependent manner, as shown in Examples and Experimental Examples below, in which a large aqueous solution of artificial ethanol (80% (v / v) . Here, 3T3-L1 cells are lipogenic precursor cells derived from mouse embryos, which are widely used as an in vitro model of obesity research.

In view of the above-mentioned experimental results, the composition for anti-obesity of the present invention is characterized by containing a large-sized alien extract as an active ingredient thereof.

In the present specification, the term "large-sized alien extract" refers to a large alien stem, leaf, fruit, flower, roots, mixture thereof and the like to be extracted with water, a lower alcohol having 1 to 4 carbon atoms such as methanol, ethanol, and butanol, (DMF), dimethylsulfoxide (DMSO), 1,3-butylene glycol, propylene glycol, or a mixed solvent thereof is used as the organic solvent, for example, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate Extracts obtained by extracting with supercritical extraction solvents such as carbon dioxide and pentane or fractions obtained by fractionating the extracts, and the extraction method refers to a method of extracting the extracts obtained by extracting the extracts using a method of extracting the extracts using a method of extracting , Heating, ultrasonic irradiation, supercritical extraction, and the like can be applied. In the case of the fractionated extract, the fraction is suspended in a specific solvent and then mixed with a solvent having a different polarity. The extract is adsorbed on a column packed with silica gel or the like, and then a hydrophobic solvent, a hydrophilic solvent, Quot; means fractions obtained as a mobile phase. Also, the meaning of the extract includes a concentrated liquid extract or a solid extract in which the extraction solvent is removed by a method such as freeze drying, vacuum drying, hot air drying, spray drying and the like. Preferably an extract obtained by using water, ethanol or a mixed solvent thereof as an extraction solvent, and more preferably an extract obtained by using a mixed solvent of water and ethanol as an extraction solvent.

In the present specification, the term " active ingredient "alone means an ingredient which exhibits the desired activity or which can exhibit activity together with a carrier which is not itself active.

In the present specification, "anti-obesity" means a decrease in body fat and / or a decrease in body weight. Thus, it includes the prevention of obesity and the treatment of obesity, and further includes the reduction of weight / body fat for beauty or health purposes (aka diet) although the weight is not classified as obesity or overweight.

In the present specification, the term "obesity" means an abnormally increased state of adipose tissue, whether it is obesity due to genetic factors or obesity due to environmental factors. When the body mass index (BMI) It is meant to include obesity (for BMI> 30.0), obesity (for BMI 25-30), and overweight (for BMI between 23 and 25).

The anti-obesity composition of the present invention may contain the active ingredient in any amount (effective amount) as long as it can exhibit anti-obesity activity, depending on the purpose of use, formulation, compounding purpose, etc. A typical effective amount is based on the total weight of the composition To < RTI ID = 0.0 > 99.999% < / RTI > by weight. Here, "effective amount" refers to the amount of active ingredient capable of inducing an anti-obesity effect. Such effective amounts can be determined experimentally within the ordinary skill of those skilled in the art.

The subject to which the composition of the present invention can be applied (prescription) is preferably a mammal and a person, particularly a human.

The anti-obesity composition of the present invention may further comprise, in addition to the active ingredient, any compound or natural extract which is already known to have safety and has anti-obesity activity for the purpose of raising or supplementing the anti-obesity effect. Specific examples of such compounds or extracts include Garcinia cambogia bark extract, conjugated linolenic acid (free fatty acid), conjugated linolenic acid (triglyceride) in the Health Functional Foods Act ), Green tea extract, chitosan, Lactobacillus gasseri BNR17, L-carnitine tartrate, green matte extract, green coffee bean extract, sesame leaf extract, soybean Extracts of ginseng extract, Extracts of Extracted Extract of Stone, Lactoferrin (Milk refining protein), Lemon balm extract powder, Mate Extract of hot water, Extract of marine extracts (Janseten), Fermented vinegar pomegranate complex, Boi tea extract, Soybean) peptide complex, vegetable oil diglyceride, wild mango seed extract, heavy chain And the like acids (MCFA) containing oil, Collet mouse force coli extract, chitooligosaccharide, finger root extract powder, combined extracts, such as hibiscus. Such compounds or natural extracts may be included in the anti-obesity composition of the present invention in combination with one or more thereof.

The anti-obesity composition of the present invention, in a specific aspect, can be identified as a food composition.

The food composition of the present invention can be prepared in any form and can be used in various forms such as beverages such as tea, juice, carbonated drink, ionic drink, processed milk such as milk and request route, gum, rice cake, Korean confectionery, Such as foods, tablets, capsules, rings, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars and the like. In addition, the food composition of the present invention may be classified into any product category as long as it meets the laws and regulations on the time of manufacture and distribution in the legal and functional category. For example, it may be a health functional food according to the Act on Health Functional Foods, or a food functional food according to the Food Sanitation Act (standards for food additives, food standards and specifications), confectionery, pulses, bean oil, fermented beverages, Particularly food preparations for weight control).

The food composition of the present invention may contain food additives in addition to the active ingredients thereof. Food additives are generally understood to be substances which are added to foods and mixed or infiltrated into food in the manufacture, processing or preservation of food, and their safety must be ensured since they are taken with food daily and for a long time. Food additives according to the Food Hygiene Act (food additives notification, food additive standards and standards) are limited by the classification of safe synthetic food additives as chemical synthetic products, natural additives and mixed preparations.

These functional food additives can be classified into sweeteners, flavors, preservatives, emulsifiers, acidifiers, and thickeners.

A sweetener is used to impart a sweet taste suitable for foods, and natural or synthetic sweeteners can be used. Preferably, natural sweeteners are used. Examples of natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose and maltose.

Flavors may be used to enhance taste or flavor, both natural and synthetic. Preferably, a natural one is used. When using natural ones, the purpose of nutritional fortification can be performed in addition to the flavor. Examples of natural flavoring agents include those obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or those obtained from green tea leaves, Asiatica, Daegu, Cinnamon, Chrysanthemum leaves and Jasmine. Also, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, banks and the like can be used. The natural flavoring agent may be a liquid concentrate or a solid form of extract. Synthetic flavors may be used depending on the case, and synthetic flavors such as esters, alcohols, aldehydes, terpenes and the like may be used.

As the preservative, calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate and EDTA (ethylenediaminetetraacetic acid) can be used. As the emulsifier, acacia gum, carboxymethyl cellulose, Pectin and the like. As the acidulant, math, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid and the like can be used. The acidulant may be added so that the food composition has a proper acidity for the purpose of inhibiting the growth of microorganisms other than the purpose of enhancing the taste.

Examples of the thickening agent include suspending agents, sedimentation agents, gel-forming agents, bulking agents and the like.

The food composition of the present invention may contain physiologically active substances or minerals which are known in the art and which are stable as a food additive in addition to the above-mentioned food additives in order to supplement and supplement functional and nutritional properties.

Examples of such physiologically active substances include catechins contained in green tea and the like, vitamins such as vitamin B1, vitamin C, vitamin E and vitamin B12, tocopherol, dibenzoyl thiamine, etc. Examples of minerals include calcium preparations such as calcium citrate, magnesium stearate , Iron preparations such as iron citrate, chromium chloride, potassium iodide, selenium, germanium, vanadium, zinc and the like.

The food composition of the present invention may contain an appropriate amount of the above-mentioned food additives according to the product type so as to achieve the purpose of addition thereof.

With regard to other food additives that can be included in the food composition of the present invention, reference may be made to the Food Code or the Food Additive Code.

In another specific embodiment, the composition of the present invention can be identified as a pharmaceutical composition.

The pharmaceutical composition of the present invention may be prepared into oral formulations or parenteral formulations according to the route of administration by conventional methods known in the art, including pharmaceutically acceptable carriers in addition to the active ingredient. The term "pharmaceutically acceptable" as used herein means that the application (prescribing) subject does not have the above-mentioned toxicity that is adaptable without inhibiting the activity of the active ingredient.

When the pharmaceutical composition of the present invention is prepared into an oral formulation, it may be formulated into powder, granules, tablets, pills, sugar tablets, capsules, solutions, gels, syrups, suspensions, wafers And the like. Examples of suitable pharmaceutically acceptable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, xylitol, starch such as corn starch, potato starch and wheat starch, cellulose, methylcellulose, ethylcellulose, Cellulose derivatives such as sodium carboxymethyl cellulose and hydroxypropylmethyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, And the like. In case of formulation, a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and / or an excipient may be formulated according to need.

When the pharmaceutical composition of the present invention is prepared into a parenteral dosage form, it may be formulated in the form of an injection, transdermal drug delivery, nasal aspirate and suppository together with a suitable carrier according to methods known in the art. Examples of suitable carrier in the case of injection preparation include sterilized water, polyol such as ethanol, glycerol or propylene glycol, or a mixture thereof. Preferably, the carrier is selected from the group consisting of Ringer's solution, phosphate buffered saline containing triethanolamine, , 5% dextrose, and the like may be used. When formulated with a transdermal drug, it can be formulated in the form of an ointment, a cream, a lotion, a gel, a solution for external use, a pasta, a liniment, or an air-roll. The nasal inhalant may be formulated in the form of an aerosol spray using a suitable propellant such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc. The suppositories may be witepsol, polyethylene glycol, cacao butter, laurin, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, sorbitan fatty acid esters and the like can be used.

The formulation of pharmaceutical compositions is well known in the art, and more details can be found in Remington ' s Pharmaceutical Sciences (19th ed., 1995) and the like. This document is considered part of this specification.

The preferred dosage of the pharmaceutical composition of the present invention is 0.001 mg / kg to 10 g / kg per day, preferably 0.001 mg / kg to 1 g / day, depending on the patient's condition, body weight, sex, age, / kg < / RTI > The administration can be carried out once or several times a day. Such dosages are not to be construed as limiting the scope of the invention in any respect.

INDUSTRIAL APPLICABILITY As described above, the present invention can provide an anti-obesity composition using a large artificial extract. The composition for anti-obesity of the present invention can be commercialized as a functional food, medicine, or the like.

Fig. 1 is a graph showing the activity of inhibiting the differentiation of precursor adipocyte of fat-derived extracts from fat cells.

Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these examples and experimental examples.

< Example > Big  Preparation of extract

The dried Arisaema ringens (outpost) was dipped in 80% ethanol, extracted for 24 hours, and then filtered through a filter paper. The filtrate was concentrated under reduced pressure and then lyophilized to obtain a large scale artificial extract.

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< Experimental Example > Big  Experiments to improve obesity of extracts

3T3-L1 (ATCC CL-173), a mouse precursor adipocyte, was cultured in a 10% BCS DMEM medium at 37 ° C and 5% CO ₂ . 3T3-L1 precursor adipocytes were plated at a density of 5 × 10 ⁴ cells / well in a 24-well plate and maintained at 100% confluency for 2 days. The precursor adipocytes were cultured in 10% FBS DMEM medium containing 0.5 mM 3-isobutyl-1-methylxanthine (Calbiochem 410957), 1 uM dexamethasone (Calbiochem 265005) and 1 ug / ml insulin (Sigma I9278) Were induced for 2 days and cultured for 48 hours with 10% FBS DMEM containing 1 ug / ml insulin for two days. Subsequently, the cells were replaced with 10% FBS DMEM medium for 2 days every 4 days. During induction of adipocyte differentiation, the extracts of the examples were treated with 50, 100 ㎍ / ml of each culture medium, and the degree of adipocyte differentiation was observed on the 8th day when the differentiation was completed. The degree of adipocyte differentiation was firstly confirmed by microscopy through Oil Red O staining. The degree of adipocyte staining was measured at 510 nm absorbance using an ELISA reader (SPECTRAmax 340PC, Molecular Devices, USA) Respectively. The results were obtained by repeating the experiment twice.

The results of quantitative analysis of fat mass are shown in [Figure 1]. Referring to [Figure 1], it can be seen that the large-scale extract of Artemisia sinensis has an activity to inhibit fat accumulation in adipocytes in a concentration-dependent manner.

Claims (4)

A food composition for an anti-obesity, comprising as an active ingredient, a water-ethanol-solvent-extracted extract of a large artificial plant.
The method according to claim 1,
Wherein the extract is an 80% ethanol extract.
A pharmaceutical composition for anti-obesity comprising as an active ingredient a water-ethanol mixed solvent extract of a large artificial outpost.
The method of claim 3,
Wherein the extract is an 80% ethanol extract.

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