JP6047545B2 - A pharmaceutical composition for preventing or treating obesity, comprising a combined extract of Sangpaxo, Kyo-Oh and Onji - Google Patents

Description

  The present invention relates to a composition for preventing or treating obesity, comprising a combined extract of saxophone, kyoto and onji. More specifically, the present invention relates to a pharmaceutical composition for preventing or treating obesity, a food composition, and the above-mentioned composite, comprising a combined extract of Sangpaxo, Kyouyou and Onji, or a combined extract of Sangpaxo, Kyoujo, Onji, and Sekisho. The present invention relates to a method for producing an extract.

  Obesity generally means that there is an excess of adipose tissue in the body, and energy taken from food cannot balance with energy consumed by physical activity, etc., and excess energy accumulates as body fat It is a phenomenon. When body fat becomes abnormally high due to long-term energy imbalance, various metabolic diseases and lifestyle-related diseases such as diabetes, hyperlipidemia, heart disease, stroke, arteriosclerosis, fatty liver are induced, This has emerged as a serious social problem not only in Western Europe but also in Korea.

  Obesity occurs due to various causes such as genetic factors, environmental factors due to westernized diet, psychological factors due to stress, and abnormalities in energy metabolism. The types are classified into simple obesity due to overeating and lack of exercise depending on the cause, and symptomatic obesity due to endocrine, hypothalamic, hereditary, metabolic, and the like.

  There are a method for measuring body weight and a method for measuring the thickness of skin wrinkles. Generally, an obesity index of 25 or more is defined as obesity. The body mass index (BMI) is the weight (kg) divided by the square of the height (m), which is 30 or more for Westerners. In Korea, more than 25 are evaluated as obese.

Multilateral research is underway worldwide for the development of anti-obesity agents. Drugs for the treatment of obesity are broadly divided into emotion regulation mechanisms related to fat absorption suppression, lipolysis and fever promotion, appetite and satiety, protein metabolism inhibition, and food intake. Representative obesity therapeutics, and orlistat inhibit fat absorption and (orlistat) as a starting material Xenical ^{TM (Xenical TM),} sibutramine and (sibutramine) as a main raw material, suppress the appetite and stimulates the sympathetic nervous system Reductil ^TM (Reductil ^TM ). However, in the Xenical ^TM, fatty stools, abdominal pain, vomiting, itching, and side effects such as liver damage have been reported, in the Reductil ^TM, headache, loss of appetite, insomnia, as well as side effects such as Bin泌, serious In recent years, controversies such as the strengthening of usage standards have arisen because it causes various cardiovascular side effects.

  In addition to drug therapy using such anti-obesity agents, methods for preventing and treating obesity include dietary therapy that limits food intake, exercise therapy that increases energy consumption, psychotherapy, behavioral therapy, and surgery. Therapies are also performed.

As a preferred method for treating obesity, the combination of promotion of energy consumption by exercise and a drug for treating obesity with few side effects has been proposed as the safest and most effective method. However, in the drugs for treating obesity, serious side effects have been reported as in the case of the above-described Xenical ^TM and Reductil ^TM , and there is no clear confidence in safety. Accordingly, there is a demand for the development of a substance that exhibits an excellent anti-obesity effect and ensures safety in the human body.

  Under these circumstances, the present inventors have made intensive efforts to find a substance having an excellent effect of treating obesity without causing side effects on the human body. As a result, the combined extract of Sangpaxo, Kyoukou and Onji is not toxic to cells. It was confirmed that the prevention and treatment effects on obesity were shown in the range, and the present invention was completed.

  An object of the present invention is to provide a method for preventing or treating obesity, which comprises the step of administering a combined extract of Sangakuso, Kyouyou and Onji or a fraction thereof to an individual in need thereof in an effective amount. .

  The present invention also provides a method for preventing or treating obesity, comprising the step of administering a combined extract of Sangpaxo, Kyo-Oh, Onji, and Sekisho or a fraction thereof to an individual in need thereof in an effective amount. With the goal.

  Furthermore, the present invention includes a step of extracting a sample containing sanpaxo, kyoto and onji with water, a C1-C4 alcohol or a mixed solvent thereof to obtain an extract, and the combined extract of sanpaxo, kyoto and onji. An object is to provide a manufacturing method.

  Furthermore, the present invention includes a step of extracting a sample containing Sangakuso, Kyojo, Onji, and Sekisho with water, a C1-C4 alcohol, or a mixed solvent thereof to obtain an extract. It aims at providing the manufacturing method of a composite extract.

  Furthermore, an object of the present invention is to provide a composition comprising a combined extract of sanpaxo, kyoto and onji or a fraction thereof.

  Furthermore, an object of the present invention is to provide a composition containing a combined extract of Sangpaxo, Kyo-Oh, Onji, and Sekisho, or a fraction thereof.

  To achieve the above object, one embodiment of the present invention is to prevent or treat obesity comprising a combined extract of Sangpaxo, Kyoukou and Onji, a combined extract of Sangpaxo, Kyoukou, Onji and Sekisho, or a fraction thereof. A pharmaceutical composition is provided.

  The term “Saururus chinensis Baill.” In the present invention means a perennial herb belonging to the family Plepidoptera, which has been used as a medicinal material for traditional Chinese medicine. The saxophone has a bitter taste, is spicy, and has white flowers and roots. When the flower blooms, 2 to 3 leaves of the upper part turn white. It is known.

  The saxophone in the present invention may be used as an active ingredient of a pharmaceutical composition for preventing or treating obesity, and the site used may be a leaf, a stem, a root, or a whole plant site.

  In the present invention, “Curcumae Longae Rhizoma” means a perennial herb of the ginger family ginger that has been used as a medicinal material for traditional Chinese medicine. Kyo-o is tasteful and bitter, the surface of the rhizome is light yellow, the inside is vermilion, it has a camphor-like scent, and the ears are attached to the leaves before the leaves. Is known to bloom.

  The above-mentioned Kyou-o in the present invention may be used as an active ingredient of a pharmaceutical composition for preventing or treating obesity, and in this case, the site to be used may be a stem or a root part.

  In the present invention, “Polygalae Radix” means a perennial herb belonging to the order of Leguminosae, which has been used as a medicinal material for traditional Chinese medicine. The Onji is spicy, bitter, thick, long, streaked, has almost no hair except the slightly bent hair at the top, and blooms red-purple flowers from July to August. It is known that it is a fruit that is divided into bunches and contains many seeds.

  The onji in the present invention may be used as an active ingredient of a pharmaceutical composition for preventing or treating obesity, and in this case, the site used may be a root part.

  “Acori Gramineri Rhizoma” in the present invention means a perennial herb of the taro family Araceae that has been used as a medicinal material for traditional Chinese medicine. The petals have rhizomes that extend sideways and have beard roots from nodes, and the internodes are long in the ground, but the ones that appear on the ground are short in internodes and are green overall, with a stamen in one flower. It is an amphibious flower with both pistil, yellow flowers bloom from June to July, and it is known that it is divided into several bunches and contains many seeds.

  The said pepper in this invention may be used as an active ingredient of the pharmaceutical composition for prevention or treatment of obesity, and the site | part used may be a site | part of a stem and a root.

  The “composite extract” in the present invention is a composite extract obtained by extracting a sample containing the above-mentioned Sangpaxo, Kyoujou and Onji, or obtained by extracting a sample containing the above-mentioned Sangpaxo, Kyoujou, Onji and Sekisho. Means composite extract. In plants, the presence or absence of activity of each extract or its fraction, the degree of activity, and the specific components contained therein may differ depending on the extraction site. The present inventors have found that a whole extract of a saxophone plant, a stalk and root part of Syrian butterfly and a root part of Onji root, or a whole Santakuxan plant, a stalk and root part of Syria, a root part of Onji and Sekisho. It was first elucidated that the combined extract of the stem and root parts of the plant shows the effect of preventing or treating obesity.

  The composite extract in the present invention may be used as an active ingredient of a pharmaceutical composition for the prevention or treatment of obesity, and the content of saxophone, leopard and onji contained in the sample for obtaining the composite extract is obesity. Although it will not specifically limit if it is used for manufacture of the composition which shows the preventive or therapeutic effect of this, The mixing ratio of the saxophone, the Kyodo, and Onji contained in the said sample is 1: 0.2-1. : 0.2-1 (w / w / w) is preferable, and the mixing ratio is more preferably 1: 0.4-1: 0.4-1 (w / w / w), Most preferably, the mixing ratio is 1: 0.6: 1 (w / w / w).

  In addition, when a composite extract is obtained from a sample containing the above-mentioned Sangpaxo, Kyo-Oh, Onji, and Sekisho, the content of Sangpaxo, Kyou-Oh, Onji, and Seki contained in the sample is a composition that exhibits an effect of preventing or treating obesity. Although it is not particularly limited as long as it is used for production, the mixing ratio of saxophone, leopard, onji, and ginger contained in the sample is 1: 0.2 to 1: 0.2 to 1: The mixing ratio is preferably 0.2 to 1 (w / w / w / w), and the mixing ratio is 1: 0.4 to 1: 0.4 to 1: 0.4 to 1 (w / w / w / More preferably, the mixing ratio is 1: 0.6: 1: 0.4 (w / w / w / w). In addition, the above-mentioned sanpaxo, kyoto, onji, and ginger may be purchased and used commercially, or those collected or cultivated from nature may be used.

  The extraction method is not limited to these, but it is preferable to use a method such as hot water extraction, hot water extraction, cold immersion extraction, reflux cooling extraction, or ultrasonic extraction.

  The said extract can be manufactured by extracting with an extraction solvent or adding an fractionation solvent to the extract manufactured by extracting with an extraction solvent, and fractionating. The extraction solvent is not limited to these, but water, an organic solvent, or a mixed solvent thereof can be used. Examples of the organic solvent include alcohols having 1 to 4 carbon atoms, ethyl acetate, and acetone. Or a non-polar solvent of hexane or dichloromethane, or a mixed solvent thereof. Moreover, it is preferable to use water, a C1-C4 alcohol, or those mixed solvents, and it is more preferable to use ethanol. In one embodiment of the present invention, an extract was prepared using 25% ethanol (EtOH) as the solvent.

  Each of the extracts may be included in an amount of 0.001 to 100% by weight, more preferably 0.1 to 80% by weight, based on the total weight of the pharmaceutical composition.

  The “fraction of composite extract” in the present invention means a result obtained by a fractionation method for separating a specific component or a specific group from each composite extract.

  The fraction in the present invention can be obtained by applying various fractionation methods to the composite extract, but the fractionation method is not particularly limited to these, but various Fractionation by treating different solvents, ultrafiltration fractionation by passing through an ultrafiltration membrane with a constant molecular weight cut-off, various chromatographies (size, charge, hydrophobicity or affinity) Chromatographic fractionation method, etc.) for the separation by In particular, the solvent used in the solvent fractionation method is not particularly limited, but a polar solvent or a nonpolar solvent can be used, and a nonpolar solvent is preferably used. The solvent fractionation method can be used as a method for fractionating the composite extract in order from a solvent having a high nonpolar level to a solvent having a low non-polar level. For example, the composite extract can be used in order using hexane or ethyl acetate. A method of fractionation can be used.

  Each of the fractions may be contained in an amount of 0.001 to 100% by weight, more preferably 0.1 to 80% by weight, based on the total weight of the pharmaceutical composition.

  The “pharmaceutical composition” in the present invention means a product produced for the purpose of preventing or treating a disease, and can be used in various forms by usual methods. For example, it can be formulated into oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, etc., and in the form of external preparations, suppositories, and sterile injectable solutions Can be

  The term “obesity” in the present invention refers to an unhealthy state due to an increase in body weight, and energy intake is more than energy consumption, and excess energy remaining without being consumed is in the form of various lipids. It means a state where it is accumulated as fat or the lipid content in blood is high. When the obesity occurs, various metabolic diseases such as diabetes, hyperlipidemia, heart disease, stroke, arteriosclerosis, fatty liver and lifestyle-related diseases can be induced.

  The composition provided in the present invention can not only treat obesity by inhibiting adipogenesis, but also obesity-related diseases derived from obesity such as diabetes, hyperlipidemia, heart disease, stroke, arteriosclerosis, fatty liver Various metabolic diseases such as can be improved, prevented or treated.

  In the present invention, “prevention” means any action that suppresses or delays the occurrence of the obesity or obesity-related diseases by administering the composition of the present invention.

  “Treatment” in the present invention means any action that improves or suitably changes the symptoms of the obesity or obesity-related diseases by administering the composition of the present invention.

  According to one embodiment of the present invention, a hot water extract (composite extract or individual extract), a hot water extract (composite extraction) of a sample containing Sangaku, Kyo-Oh, Onji, and Sekisho or a sample containing each of the above components individually Product or individual extract) or ethanol extract (complex extract or individual extract), respectively (Table 1), and each of the extracts was treated with 3T3-L1 cells at various concentrations (Table 2) in As a result of verifying the anti-obesity effect in vitro, among the hot water extract (FIGS. 1a to 1c), the hot water extract (FIGS. 2a to 2c), or the ethanol extract (FIGS. 3a to 3c), a composite extract And Onji extract showed a fat content reducing effect and a cell number reducing effect, and it was confirmed that Sangpax extract, Kyoyou extract and Japanese pepper extract had no fat content reducing effect and cell number reducing effect. Moreover, it was confirmed that among the hot water extract, hot water extract, and ethanol extract, the ethanol extract is most excellent in fat content reduction effect and safety. Furthermore, each extract was administered to mice fed with a high-fat diet at various contents (Table 3), and the in vivo anti-obesity effect of each extract was verified. As a result, Onji extract and complex extract (ethanol The most effective weight loss effect was shown in mice administered the extract), of which the Onji extract showed serious toxicity, whereas the complex extract (ethanol extract) was confirmed to be less toxic ( Fig. 4); As a result of measuring the fat weight, the ingredient that has the greatest influence on the fat increase inhibitory effect is Onji, the next is Kyo-Oh, and it is analyzed that the pepper contributes the least to the fat increase inhibitory effect ( In Fig. 6), liver tissue (Fig. 7) and kidney tissue (Fig. 8), it was confirmed that the composite extract (ethanol extract) showed higher safety than Onji extract.

  According to another embodiment of the present invention, among the components contained in the composite extract, the remaining extract of Sampaku, Kyo-o and Onji, except for the red pepper analyzed to have the least contribution to the effect of suppressing the increase in fat. In order to confirm the obesity-suppressing effect, each ethanol extract was obtained for a sample that always contained sanpaxo, kyou-o, and onji, and that selectively contained ginger and clover (Table 4). Each ethanol extract obtained in the previous period was administered to mice at various doses to obtain each experimental animal (Table 5). The experimental animal obtained as described above was subjected to body weight (FIG. 9), food intake ( FIG. 10), fat weight (FIGS. 11a-11d), ghrelin levels (FIGS. 12a-12c), leptin levels (FIG. 13) and blood component levels (FIGS. 14a-14k) were evaluated. As a result, it was confirmed that not only the combined extract of Sangpaxo, Kyo-Oh, and Onji but also the combined extract containing ginger showed an improved anti-obesity effect compared to the control group.

  Accordingly, it has been found that the composite extract contained in the anti-obesity composition of the present invention is obtained from a sample that always contains saxophone, leopard, and onji, or in addition, additionally contains a pepper.

  The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable diluent, excipient or carrier. The composition comprising a pharmaceutically acceptable carrier can be in various dosage forms, oral or parenteral. In the case of formulating, it is prepared using a diluent or excipient such as a filler, a bulking agent, a binder, a wetting agent, a disintegrant, and a surfactant that are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and these solid preparations contain at least one excipient such as starch, It is prepared by mixing calcium, sucrose or lactose, gelatin and the like. In addition to ordinary excipients, lubricants such as magnesium stearate and talc are also used. Examples of liquid preparations for oral administration include suspensions, internal solutions, emulsions, syrups, and the like, and various excipients such as water and liquid paraffin, which are commonly used diluents, Wetting agents, sweeteners, fragrances, preservatives and the like may be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilizers, suppositories. Examples of non-aqueous solvents and suspending agents include vegetable oils such as propylene glycol, polyethylene glycol, olive oil, and injectable esters such as ethyl oleate. As a suppository base, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycero gelatin and the like are used.

  The pharmaceutical composition is a group consisting of tablets, pills, powders, granules, capsules, suspensions, liquids for internal use, emulsions, syrups, sterile aqueous solutions, non-aqueous solvents, freeze-dried agents, and suppositories. It can have any one dosage form selected from

  In order to achieve the above object, according to another embodiment of the present invention, there is a possibility that obesity may occur in a pharmaceutical composition for preventing or treating obesity comprising the composite extract or a fraction thereof as an active ingredient. Or a method of preventing or treating obesity comprising administering to an individual who has developed. At this time, each active ingredient contained in the composite extract is the same as described above.

  The “individual” in the present invention means any animal including a human who has developed or is likely to develop obesity.

  “Administration” in the present invention means an act of introducing the pharmaceutical composition of the present invention into an individual by any appropriate method.

  Administration of the pharmaceutical composition in the present invention can be performed via any common route as long as it can reach the target tissue. The pharmaceutical composition of the present invention is orally administered, buccal administration, rectal administration, topical administration, intraperitoneal administration, intravenous administration, intraarterial administration, intramuscular administration, nasal administration, subcutaneous administration, depending on the purpose. It can be administered by methods such as intradermal administration, transdermal administration, intranasal administration, pulmonary administration, rectal administration, and ocular administration, but is not limited thereto. The pharmaceutical composition can also be administered by any device that allows the active substance to migrate to the target cells.

  A pharmaceutical composition according to an embodiment of the present invention includes the complex extract. Although the content of the complex extract contained in the composition is not particularly limited, it can be contained at 0.1 to 50% by weight based on the total weight of the pharmaceutical composition.

  The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount, and the “pharmaceutically effective amount” in the present invention means a reasonable benefit / risk applicable to medical treatment. Means the amount sufficient to treat the disease, the effective dose level is the individual type and severity, age, gender, drug activity, drug sensitivity, administration time, route of administration and excretion rate, treatment The period is determined by factors including drugs used at the same time and other factors known in the medical field. The pharmaceutical composition of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents. Single or multiple doses can be administered. It is important to administer all the above factors in such an amount that the maximum effect is obtained with the minimum amount without side effects.

  The dosage of the obesity prevention or treatment pharmaceutical composition of the present invention is determined in consideration of the purpose of use, the severity of the disease, the age, weight, sex, medical history, or type of substance used as an active ingredient. A person skilled in the art can decide. As an example, the pharmaceutical composition of the present invention can be administered at a dosage of about 1 μg / kg / day to 100 mg / kg / day, preferably 20-30 mg / kg / day per adult. The frequency of administration of the pharmaceutical composition is not particularly limited, but it may be administered once a day or may be administered in several divided doses.

  In order to achieve the above object, still another embodiment of the present invention provides a food composition for preventing or improving obesity comprising the composite extract or a fraction thereof.

  Sampaku, Kyo-Oh, Onji and Sekisho contained in the composite extract have been used as a Chinese herbal medicine for a long period of time, and their safety has been proven, so they can be eaten regularly, and prevention or improvement of obesity It can be manufactured and ingested as a form of food that can be achieved. At this time, the content of the composite extract or a fraction thereof contained in the food is not particularly limited, but is 0.01 to 100% by weight based on the total weight of the food composition. Preferably it may be contained at 1 to 80% by weight. When food is a beverage, it can be contained in a proportion of 1 to 30 g, preferably 3 to 20 g based on 100 ml. In addition, the composition may include additional components that are commonly used in food compositions to improve aroma, taste, vision, and the like. For example, vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid and the like may be included. Moreover, minerals, such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), can be included. In addition, amino acids such as lysine, tryptophan, cysteine, and valine can be included. In addition, preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), bactericides (such as salicy powder and advanced salicy powder, sodium hypochlorite), antioxidants (butylhydroxyanisole (BHA), Butylhydroxytoluene (BHT), colorants (tar pigments, etc.), color formers (sodium nitrite, etc.), bleaches (sodium sulfite), seasonings (sodium glutamate (MSG), etc.), sweeteners (zultin, tichro) , Saccharin, sodium, etc.), fragrances (vanillin, lactones, etc.), swelling agents (alum, D-potassium hydrogen tartrate, etc.), tougheners, emulsifiers, thickeners (glue), coating agents, gum bases, foam inhibitors Food additives such as solvents, improvers, etc. can be added. The additive is selected according to the type of food and used in an appropriate amount.

  On the other hand, a functional food for preventing or improving obesity can be produced using a food composition containing the composite extract or a fraction thereof.

  As a specific example, a processed food that can prevent or improve obesity can be produced using the food composition. Such processed foods include, for example, confectionery, beverages, alcoholic beverages, fermented foods, canned foods, processed milk products, processed meat products, and noodles. The confectionery includes biscuits, pies, cakes, breads, candy, jelly, gum, cereals (including meal substitutes such as cereal flakes) and the like. Beverages include drinking water, carbonated beverages, functional ion beverages, juices (for example, apples, pears, grapes, aloe, mandarin oranges, peaches, carrots, tomato juices, etc.), shikke (food meals) and the like. Sake includes sake, whiskey, shochu, beer, western liquor, fruit liquor and the like. Fermented foods include soy sauce, miso, and gochujang. Canned products include canned marine products (for example, canned tuna, mackerel, saury, turban shell, etc.), canned livestock (such as canned beef, pork, chicken, turkey), and canned agricultural products (canned corn, peach, pineapple, etc.). Processed milk products include cheese, butter, yogurt and the like. Processed meat products include tonkatsu, beef cutlet, chicken cutlet, sausage, sweet and sour pork, nuggets, and nobiani. Noodles include hermetically sealed raw noodles. In addition to these, the composition can be used for retort foods, soups and the like.

  The term “functional food” in the present invention is synonymous with food for special health use (FoSHU), and is processed so that a biological regulation function can be efficiently expressed in addition to nutrition supply. It means foods with high medical and medical effects, and these foods are manufactured in various forms such as tablets, capsules, powders, granules, liquids, pills, etc. in order to obtain useful effects for the prevention or improvement of bone diseases can do.

  In order to achieve the above object, still another embodiment of the present invention includes a step of extracting a sample containing saxophone, leopard, and onji with water, a C1-C4 alcohol, or a mixed solvent thereof to obtain an extract. A method for producing the composite extract containing the present invention is provided.

  In the method for producing the composite extract, a normal extraction method in the industry such as a hot water extraction method, a hot water extraction method, an ethanol extraction method, an ultrasonic extraction method, a filtration method, and a reflux extraction method can be used. The extract may further comprise filtering, concentrating or lyophilizing the extract.

  In order to achieve the above object, still another embodiment of the present invention includes a step of extracting a sample containing saxophone, leopard, and onji with water, a C1-C4 alcohol, or a mixed solvent thereof to obtain an extract. A method for producing a combined extract of sanpaxo, kyou-o and onji is provided. At this time, each active ingredient contained in the composite extract is the same as described above.

  The sample may contain saxophone, kyoto and onji at a ratio of 1: 0.2 to 1: 0.2 to 1 (w / w / w).

  In order to achieve the above object, according to another embodiment of the present invention, an extract is obtained by extracting a sample containing saxophone, leopard, onji, and ginger with water, a C1-C4 alcohol, or a mixed solvent thereof. Provided is a method for producing a combined extract of saxophone, leopard, onji and lichen comprising steps. At this time, each active ingredient contained in the composite extract is the same as described above.

  The sample may include Sangpaxo, Kyo-Oh, Onji, and Sekisho at a ratio of 1: 0.2 to 1: 0.2 to 1: 0.2 to 1 (w / w / w / w). .

  In order to achieve the above object, still another embodiment of the present invention provides a composition comprising a combined extract of Sangpax, Kyouyou and Onji, or a fraction thereof. At this time, each active ingredient contained in the composite extract is the same as described above.

  The composition may be for the treatment of obesity.

  The composite extract may be an extract of a sample in which saxophone, kyoto, and onji are mixed at a ratio of 1: 0.2 to 1: 0.2 to 1 (w / w / w).

  The composite extract may be obtained using 25% ethanol (EtOH).

  In order to achieve the above object, still another embodiment of the present invention provides a composition comprising a combined extract of Sangpaxo, Kyoyou, Onji, and Sekisho or fractions thereof. At this time, each active ingredient contained in the composite extract is the same as described above.

  The composition may be for the treatment of obesity.

  The composite extract is extracted from a sample in which saxophone, kyoto, onji, and ginger are mixed at a ratio of 1: 0.2 to 1: 0.2 to 1: 0.2 to 1 (w / w / w / w). It may be a thing.

  The composite extract may be obtained using 25% ethanol (EtOH).

  Since the composition containing the composite extract of the present invention has no cytotoxic side effects and can inhibit adipogenesis, it can be widely used for the prevention, improvement or treatment of obesity or obesity-related diseases.

It is a figure which shows the inhibitory effect of the KIOM-2012Ob (1) hot water extract with respect to the accumulation of neutral fat in the fat cell differentiated from 3T3-L1 by oil red O staining. When inducing differentiation from 3T3-L1, it was treated with KIOM-2012Ob and its composition crude drug hot water extract, and oil red O staining was performed 8 days later. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (1), and the sampaxo, kyoto, onji, and gypsum composing KIOM-2012Ob (1) were treated according to the composition content. * Indicates significance (P <0.05) for reduced triglyceride accumulation compared to control group (0 μg / mL). It is a figure which shows the inhibitory effect of the KIOM-2012Ob (2) hot water extract with respect to the accumulation of neutral fat in the fat cell differentiated from 3T3-L1 by oil red O staining. When inducing differentiation from 3T3-L1, it was treated with KIOM-2012Ob and its composition crude drug hot water extract, and oil red O staining was performed 8 days later. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (2), and Sangpaxo, Kyoujo, Onji, and Sekisho constituting KIOM-2012Ob (2) were treated according to the composition content. * Indicates significance (P <0.05) for reduced triglyceride accumulation compared to control group (0 μg / mL). It is a figure which shows the inhibitory effect of the KIOM-2012Ob (3) hot water extract with respect to the accumulation of neutral fat in the fat cell differentiated from 3T3-L1 by oil red O staining. When inducing differentiation from 3T3-L1, it was treated with KIOM-2012Ob and its composition crude drug hot water extract, and oil red O staining was performed 8 days later. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (3), and Sangpaxo, Kyoujo, Onji, and Sekisho constituting KIOM-2012Ob (3) were treated according to the composition content. * Indicates significance (P <0.05) for reduced triglyceride accumulation compared to control group (0 μg / mL). It is a figure which shows the influence of the KIOM-2012Ob (1) hot water extract on the survival rate of the cell differentiated from 3T3-L1. The survival rate of the cell differentiated from 3T3-L1 is shown by measuring by the WST method. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (1), and the sampaxo, kyoto, onji, and gypsum composing KIOM-2012Ob (1) were treated according to the composition content. The $ symbol indicates significance (P <0.05) for the decrease in cell viability compared to the control group (0 μg / mL). It is a figure which shows the influence of the KIOM-2012Ob (2) hot water extract on the survival rate of the cell differentiated from 3T3-L1. The survival rate of the cell differentiated from 3T3-L1 is shown by measuring by the WST method. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (2), and Sangpaxo, Kyoujo, Onji, and Sekisho constituting KIOM-2012Ob (2) were treated according to the composition content. The $ symbol indicates significance (P <0.05) for the decrease in cell viability compared to the control group (0 μg / mL). It is a figure which shows the influence of the KIOM-2012Ob (3) hot water extract on the survival rate of the cell differentiated from 3T3-L1. The survival rate of the cell differentiated from 3T3-L1 is shown by measuring by the WST method. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (3), and Sangpaxo, Kyoujo, Onji, and Sekisho constituting KIOM-2012Ob (3) were treated according to the composition content. The $ symbol indicates significance (P <0.05) for the decrease in cell viability compared to the control group (0 μg / mL). It is a figure which shows the inhibitory effect of the KIOM-2012Ob (1) DW extract (distilled water extract) with respect to the accumulation | storage of the neutral fat in the fat cell differentiated from 3T3-L1 by oil red O dyeing | staining. When inducing differentiation from 3T3-L1, it was treated with KIOM-2012Ob and its composition crude drug hot water extract, and oil red O staining was performed 8 days later. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (1), and the sampaxo, kyoto, onji, and gypsum composing KIOM-2012Ob (1) were treated according to the composition content. * Indicates significance (P <0.05) for reduced triglyceride accumulation compared to control group (0 μg / mL). It is a figure which shows the inhibitory effect of the KIOM-2012Ob (2) DW extract (distilled water extract) with respect to the accumulation of neutral fat in the fat cell differentiated from 3T3-L1 by oil red O staining. When inducing differentiation from 3T3-L1, it was treated with KIOM-2012Ob and its composition crude drug hot water extract, and oil red O staining was performed 8 days later. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (2), and Sangpaxo, Kyoujo, Onji, and Sekisho constituting KIOM-2012Ob (2) were treated according to the composition content. * Indicates significance (P <0.05) for reduced triglyceride accumulation compared to control group (0 μg / mL). It is a figure which shows the inhibitory effect of the KIOM-2012Ob (3) DW extract (distilled water extract) with respect to the accumulation of neutral fat in the fat cell differentiated from 3T3-L1 by oil red O staining. When inducing differentiation from 3T3-L1, it was treated with KIOM-2012Ob and its composition crude drug hot water extract, and oil red O staining was performed 8 days later. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (3), and Sangpaxo, Kyoujo, Onji, and Sekisho constituting KIOM-2012Ob (3) were treated according to the composition content. * Indicates significance (P <0.05) for reduced triglyceride accumulation compared to control group (0 μg / mL). It is a figure which shows the influence of KIOM-2012Ob (1) DW extract (distilled water extract) on the survival rate of the cell differentiated from 3T3-L1. The survival rate of the cell differentiated from 3T3-L1 is shown by measuring by the WST method. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (1), and the sampaxo, kyoto, onji, and gypsum composing KIOM-2012Ob (1) were treated according to the composition content. The $ symbol indicates significance (P <0.05) for the decrease in cell viability compared to the control group (0 μg / mL). It is a figure which shows the influence of KIOM-2012Ob (2) DW extract (distilled water extract) on the survival rate of the cell differentiated from 3T3-L1. The survival rate of the cell differentiated from 3T3-L1 is shown by measuring by the WST method. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (2), and Sangpaxo, Kyoujo, Onji, and Sekisho constituting KIOM-2012Ob (2) were treated according to the composition content. The $ symbol indicates significance (P <0.05) for the decrease in cell viability compared to the control group (0 μg / mL). It is a figure which shows the influence of KIOM-2012Ob (3) DW extract (distilled water extract) on the survival rate of the cell differentiated from 3T3-L1. The survival rate of the cell differentiated from 3T3-L1 is shown by measuring by the WST method. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (3), and Sangpaxo, Kyoujo, Onji, and Sekisho constituting KIOM-2012Ob (3) were treated according to the composition content. The $ symbol indicates significance (P <0.05) for the decrease in cell viability compared to the control group (0 μg / mL). The $$ mark indicates significance (P <0.01) for the decrease in cell viability compared to the control group (0 μg / mL). It is a figure which shows the inhibitory effect of the KIOM-2012Ob (1) 25% EtOH extract with respect to the accumulation of neutral fat in the fat cells differentiated from 3T3-L1 by oil red O staining. When inducing differentiation from 3T3-L1, it was treated with KIOM-2012Ob and its composition crude drug hot water extract, and oil red O staining was performed 8 days later. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (1), and the sampaxo, kyoto, onji, and gypsum composing KIOM-2012Ob (1) were treated according to the composition content. * Indicates significance (P <0.05) for reduced triglyceride accumulation compared to control group (0 μg / mL). It is a figure which shows the inhibitory effect of the KIOM-2012Ob (2) 25% EtOH extract with respect to the accumulation of neutral fat in the fat cells differentiated from 3T3-L1 by oil red O staining. When inducing differentiation from 3T3-L1, it was treated with KIOM-2012Ob and its composition crude drug hot water extract, and oil red O staining was performed 8 days later. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (2), and Sangpaxo, Kyoujo, Onji, and Sekisho constituting KIOM-2012Ob (2) were treated according to the composition content. * Indicates significance (P <0.05) for reduced triglyceride accumulation compared to control group (0 μg / mL). It is a figure which shows the inhibitory effect of the KIOM-2012Ob (3) 25% EtOH extract with respect to the accumulation of neutral fat in the fat cells differentiated from 3T3-L1 by oil red O staining. When inducing differentiation from 3T3-L1, it was treated with KIOM-2012Ob and its composition crude drug hot water extract, and oil red O staining was performed 8 days later. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (3), and Sangpaxo, Kyoujo, Onji, and Sekisho constituting KIOM-2012Ob (3) were treated according to the composition content. * Indicates significance (P <0.05) for reduced triglyceride accumulation compared to control group (0 μg / mL). It is a figure which shows the influence of KIOM-2012Ob (1) 25% EtOH extract on the survival rate of the cell differentiated from 3T3-L1. The survival rate of the cell differentiated from 3T3-L1 is shown by measuring by the WST method. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob, and Sangpaxo, Kyoujo, Onji, and Sekisho, which constitute KIOM-2012Ob (1), were treated according to the composition content. The $ symbol indicates significance (P <0.05) for the decrease in cell viability compared to the control group (0 μg / mL). The $$ mark indicates significance (P <0.01) for the decrease in cell viability compared to the control group (0 μg / mL). It is a figure which shows the influence of KIOM-2012Ob (2) 25% EtOH extract on the survival rate of the cell differentiated from 3T3-L1. The survival rate of the cell differentiated from 3T3-L1 is shown by measuring by the WST method. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob, and Sangpaxo, Kyoujo, Onji, and Sekisho, which constitute KIOM-2012Ob (2), were treated according to the composition content. The $ symbol indicates significance (P <0.05) for the decrease in cell viability compared to the control group (0 μg / mL). * Indicates significance (P <0.05) for improving cell viability of KIOM-2012Ob (2) EtOH extract compared to cell viability of Onji 25% EtOH extract. It is a figure which shows the influence of the KIOM-2012Ob (3) 25% EtOH extract on the survival rate of the cell differentiated from 3T3-L1. The survival rate of the cell differentiated from 3T3-L1 is shown by measuring by the WST method. The treatment concentration in the graph indicates the concentration of KIOM-2012Ob (3), and Sangpaxo, Kyoujo, Onji, and Sekisho constituting KIOM-2012Ob (3) were treated according to the composition content. The $ symbol indicates significance (P <0.05) for the decrease in cell viability compared to the control group (0 μg / mL). The $$ mark indicates significance (P <0.01) for the decrease in cell viability compared to the control group (0 μg / mL). * Indicates the significance (P <0.05) for improving cell viability of KIOM-2012Ob (3) EtOH extract compared to cell viability of Onji 25% EtOH extract. It is a figure which shows the weight loss effect in the obesity animal model of a KIOM-2012Ob 25% EtOH extract. Normal control group given only 10% high fat diet, negative control group given only 60% high fat diet, positive (Xenical, 62.5 mg / kg) + 60% high fat diet positive ( positive) A control group was used. In the extract treatment group, 1X is an extract dose based on a decoction taken by an adult male per day, and 4X is a dose 4 times the dose. The KIOM-2012Ob-4X group shows significant weight loss. It is a figure which shows the food intake of the mouse | mouth which gave the KIOM-2012Ob 25% EtOH extract. * Indicates significance (P <0.05) for a decrease in food intake of mice given KIOM-2012Ob (3) EtOH extract compared to food intake of 60% HFD mice. It is a figure which shows the fat accumulation inhibitory effect of KIOM-2012Ob 25% EtOH extract. Normal control group given only 10% high fat diet, negative (HFD, negative) control group given only 60% high fat diet, Xenical (62.5 mg / kg) + 60% high fat diet A positive control group was used. Mouse adipose tissue was weighed for abdominal and subcutaneous fat. ** indicates significance (P <0.05) for the reduction in the weight of abdominal fat in mice given KIOM-2012Ob (3) EtOH extract compared to the weight of abdominal fat in 60% HFD mice. It is a figure which shows the influence which it has on the liver of a KIOM-2012Ob 25% EtOH extract. The liver tissue was fixed with formalin, and H & E tissue staining and pathological findings were requested. A shows an increase in microvesicular lipoma in the liver tissue, indicating that the increase in microvesicular lipoma was suppressed in the KIOM-2012Ob treatment group. B shows an increase in chronic inflammation in the liver. It shows that the treatment group of KIOM-2012Ob is significantly (P <0.05, P <0.01) less than the other herbal extract treatment groups, particularly the Onji extract treatment group. The $$ mark indicates the significance (P <0.01) for the increase in microvesicular lipoma compared to the normal control group. The $ mark indicates significance (P <0.05) for the increase in microvesicular lipoma compared to the normal control group. ** indicates the significance (P <0.01) for the reduction of chronic inflammation in the KIOM-2012Ob treated group compared to the Onji extract-4X treated group. * Indicates significance (P <0.05) for reduction of chronic inflammation in the KIOM-2012Ob treated group compared to Onji extract-4X treated group. ## indicates a significance (P <0.01) for an increase in chronic inflammation compared to the negative control group (Negative control). The # symbol indicates significance (P <0.05) for an increase in chronic inflammation compared to the negative control group (Negative control). It is a figure which shows the influence which it has on the kidney of KIOM-2012Ob 25% EtOH extract. Kidney tissue was fixed in formalin and H & E tissue staining and pathological findings were requested. It shows an increase in chronic inflammation in the kidney. In the treatment group of KIOM-2012Ob, it was shown that it decreased significantly (P <0.05, P <0.01) from the other crude drug extract treatment groups, particularly from the Onji extract treatment group. ** indicates the significance (P <0.01) for the reduction of chronic inflammation in the KIOM-2012Ob treated group compared to the Onji extract-4X treated group. * Indicates significance (P <0.05) for reduction of chronic inflammation in the KIOM-2012Ob treated group compared to Onji extract-4X treated group. ## indicates a significance (P <0.001) for an increase in chronic inflammation compared to the negative control group (Negative control). ## indicates a significance (P <0.01) for an increase in chronic inflammation compared to the negative control group (Negative control). The # symbol indicates significance (P <0.05) for an increase in chronic inflammation compared to the negative control group (Negative control). It is a graph which shows the result of having compared the body weight of the animal model by the treatment dose of the extract which contains a saxophone, a leopard, and Onji, and selectively contains a pepper or a clover. It is a graph which shows the result of having compared the food intake of the animal model by the processing dose of the extract which contains a saxophone, Kyo-Oh, and Onji, and which selectively contains a pepper or a clover. It is a graph which shows the result of having compared the weight of the abdominal genital fat of the animal model by the treatment dose of the extract which contains a saxophone, a leopard, and Onji, and which selectively contains a pepper or a clover. It is a graph which shows the result of having compared the weight of the mesentery fat of the animal model by the treatment dose of the extract which contains a saxophone, a Kyou-Oh, and Onji, and which selectively contains a pepper or a clover. It is a graph which shows the result of having compared the weight of the subcutaneous fat of the animal model by the treatment dose of the extract which contains a saxophone, a kyoto, and Onji, and which selectively contains a pepper or a clover. It is a graph which shows the result of having compared the weight of the total fat of the animal model by the processing dose of the extract which contains a saxophone, a leopard and an onji, and which selectively contains a pepper or a clover. It is a graph which shows the result of having compared the level of the active form ghrelin of the animal model by the treatment dose of the extract which contains a saxophone, a leopard, and Onji, and which selectively contains a pepper or a clover. FIG. 7 is a graph showing the results of comparing the activated desacyl ghrelin levels of the animal model with treatment doses of extracts containing sampaxos, leopards, and onjis, and selectively including buffalo or clover. It is a graph which shows the result of having compared the active type ghrelin ratio level of the animal model by the treatment dose of the extract which contains a saxophone, a leopard, and Onji, and selectively contains a pepper or a clover. It is a graph which shows the result of having compared the leptin level in the plasma of the animal model by the treatment dose of the extract which contains a saxophone, a leopard and an onji, and selectively contains a pepper or a clover. It is a graph which shows the result of having compared the blood triglyceride level of the animal model by the treatment dose of the extract which contains a saxophone, a leopard and an onji, and selectively contains a pepper or a clover. It is a graph which shows the result of having compared the total cholesterol level in the blood of the animal model by the treatment dose of the extract which contains a saxophone, a Kyou-o-Oh, and Onji, and which selectively contains a pepper or a clover. It is a graph which shows the result of having compared the blood LDL cholesterol level of the animal model by the treatment dose of the extract which contains a saxophone, a leopard and an onji, and which selectively contains a pepper or a clover. It is a graph which shows the result of having compared the blood HDL cholesterol level of the animal model by the treatment dose of the extract which contains a saxophone, a leopard, and Onji, and selectively contains a pepper or a clover. It is a graph which shows the result of having compared the blood glucose level of the animal model by the treatment dose of the extract which contains a saxophone, a Kyou-Oh, and Onji, and selectively contains a pepper or a clover. It is a graph which shows the result of having compared the blood creatinine level of the animal model by the treatment dose of the extract which contains a saxophone, a leopard and an onji, and selectively contains a pepper or a clover. It is a graph which shows the result of having compared the blood urea level of the animal model by the treatment dose of the extract which contains a saxophone, a leopard and an onji, and selectively contains a pepper or a clover. It is a graph which shows the result of having compared the LDH level in the blood of the animal model by the treatment dose of the extract which contains a saxophone, a leopard and an onji, and selectively contains a pepper or a clover. It is a graph which shows the result of having compared the blood ALP level of the animal model by the treatment dose of the extract which contains a saxophone, a leopard and an onji, and which selectively contains a pepper or a clover. It is a graph which shows the result of having compared the blood GPT level of the animal model by the treatment dose of the extract which contains a saxophone, a leopard and an onji, and selectively contains a pepper or a clover. It is a graph which shows the result of having compared the blood GOT level of the animal model by the treatment dose of the extract which contains a saxophone, a leopard and an onji, and selectively contains a pepper or a clover.

  Hereinafter, the present invention will be described in more detail through examples. These examples are for explaining the present invention more specifically, and the scope of the present invention is not limited to these examples.

Manufacture of individual extract and composite extract of Sangpaxo, Kyo-Oh, Onji and Sekisho Each of Sangpaxo, Kyou-Oh, Onji and Sekisho was mixed at the ratio shown in Table 1 to obtain 30 g of the mixture, and the mixture was heated with hot water. Each applicable extract was obtained by applying to extraction, hot water extraction and ethanol extraction methods. Each extract obtained in the previous period was filtered to obtain a liquid component, and the obtained liquid component was freeze-dried to obtain a powdery extract (hot water extract, hot water extract and ethanol extract). The powdery extract was dissolved in distilled water at a concentration of 100 mg / mL and used as a sample in subsequent experiments. At this time, the hot water extraction is performed by adding 1 liter of fresh water to the mixture and heating it to 100 mL, and the hot water extraction is performed by adding 300 mL of distilled water to the mixture and maintaining at 38 ° C. for 24 hours. The ethanol extraction was performed by adding 300 mL of 25% ethanol to the mixture and extracting the mixture for 24 hours while maintaining at 38 ° C.

  In addition, 30 g of each pulverized product of Sangpaxo, Kyooh, Onji, and Sekisho was applied to the same method as described above to produce individual extracts of each component (hot water extract, hot water extract, and ethanol extract). .

In vitro anti-obesity effect of separate extracts and combined extracts of Sangpaxo, Kyo-Oh, Onji and Sekisho 3T3-L1 cells obtained from ATCC, USA, 10% bovine serum (Bovine Serum, BS, Gibco) and 1% penicillin-streptomycin Was inoculated into DMEM (Dulbcco's Modified Eagle's Medium, Lonza) medium, and cultured at 37 ° C. and 5% CO ₂ , and then subcultured at intervals of 3 to 4 days to obtain adipose precursor cells.

The preadipocytes obtained as described above are collected and titrated at a concentration of 1 × 10 ⁴ cells / mL, and then dispensed into a 96-well plate in an amount of 100 μL / well, at 37 ° C. and 5% The cells were cultured for 4 days until saturated under CO ₂ conditions. Next, adipocyte differentiation-inducing medium (DMEM, 0.25 μM dexamethasone, 0.5 mM 3-isobutyl-1-methylxanthine) containing each individual extract or composite extract produced in Example 1 in the cultured cells. 10 μg / mL insulin and FBS (Fetal Bovine Serum)) were added and further cultured for 2 days. At this time, the concentration of the individual extract or the composite extract contained in the adipocyte differentiation induction medium is as shown in Table 2 below.

  Next, the medium was removed, and a DMEM medium containing only 10 μg / mL insulin was added, followed by culturing for 2 days. Thereafter, culturing was performed for 8 days while changing the DMEM medium containing only FBS at intervals of 2 days.

  After completion of the culture, the cells were collected, washed with PBS, and then fixed with 10% formalin. The fixed cells were stained with Oil Red O and washed with 70% isopropyl alcohol. The washed cells were dried, and Oil Red O, which was stained with 100% isopropyl alcohol, was dissolved. Absorbance was measured at 490 nm, and the content of fat accumulated in the cells was calculated using the measured absorbance value. At this time, the fat content was expressed as a percentage of the average absorbance value of the control group.

  On the other hand, using the WST (Water-soluble tetrazolium, the sodium salt of 4- [3- (4iodophenyl) -2- (4-nitrophenyl) -2H-5-tetrazolio] -1,3-benzene disulfonate) measurement method, The viability of the differentiated cells was measured and the cytotoxicity of each composite extract and individual extract was evaluated. In general, cells that have been cultured are treated with a WST solution (10 μL / 100 μL), further cultured for 1 hour, and then the amount of formazan released into the culture is calculated by absorbance (520 nm) to survive. Levels were measured and expressed as a percentage of the control value.

  First, as a result of analyzing the fat accumulation inhibitory effect of the hot water extract, as shown in FIGS. 1a to 1c, each composite extract (KIOM-2012Ob (1), KIOM-2012Ob (2), KIOM-2012Ob (3 )), The fat content decreased in a concentration-dependent manner when treated at concentrations of 50 and 100 μg / mL, and only Onji extract of each individual extract showed the same fat content reducing effect as the composite extract. In addition, it was confirmed that the extract of sanpaxo, kyoto, and pepe does not show a fat content reducing effect in particular regardless of the treatment concentration. Moreover, the fat reduction rate when each composite extract (KIOM-2012Ob (1), KIOM-2012Ob (2), KIOM-2012Ob (3)) was treated at a concentration of 50 μg / mL was 10, 13 and 17, respectively. It was confirmed that the fat reduction rate when treated at a concentration of 100 μg / mL was 25, 28 and 26%, respectively.

  Moreover, as a result of analyzing the cytotoxicity of the hot water extract, as shown in FIG. 1d to FIG. 1f, each composite extract (KIOM-2012Ob (1), KIOM-2012Ob (2), KIOM-2012Ob (3)) Treated with concentrations of 50 and 100 μg / mL, the number of cells decreased in a concentration-dependent manner, and the number of cells decreased significantly when treated with Onji extract among each individual extract. It was confirmed that the number of cells did not decrease regardless of the treatment concentration.

  Next, as a result of analyzing the fat accumulation inhibitory effect of the hot water extract, as shown in FIGS. 2a to 2c, each composite extract (KIOM-2012Ob (1), KIOM-2012Ob (2), KIOM-2012Ob (3 )), The fat content decreased in a concentration-dependent manner when treated at concentrations of 50 and 100 μg / mL, and only Onji extract of each individual extract showed the same fat content reducing effect as the composite extract. In addition, it was confirmed that the extract of sanpaxo, kyoto, and pepe does not particularly show a fat content reducing effect regardless of the treatment concentration.

  Moreover, as a result of analyzing the cytotoxicity of the hot water extract, as shown in FIG. 2d to FIG. 2f, each composite extract (KIOM-2012Ob (1), KIOM-2012Ob (2), KIOM-2012Ob (3)) When treated with concentrations of 50 and 100 μg / mL, the number of cells decreased in a concentration-dependent manner, and when treated with Onji extract among individual extracts, the number of cells was greatly reduced. It was confirmed that the number of cells did not decrease regardless of the treatment concentration.

  Finally, as a result of analyzing the fat accumulation inhibitory effect of the ethanol extract, as shown in FIGS. 3 a to 3 c, each composite extract (KIOM-2012Ob (1), KIOM-2012Ob (2), KIOM-2012Ob (3 )) Reduced the fat content in a concentration-dependent manner when treated at concentrations of 10, 50 and 100 μg / mL, and only the Onji extract of each individual extract showed the same fat content reduction effect as the composite extract. As a result, it was confirmed that the extract of Sangaku, Kyou-o and Sekisho did not show a fat content reducing effect regardless of the treatment concentration.

  Moreover, as a result of analyzing the cytotoxicity of the hot water extract, as shown in FIGS. 3d to 3f, each composite extract (KIOM-2012Ob (1), KIOM-2012Ob (2), KIOM-2012Ob (3)) When treated at a concentration of 100 μg / mL, the number of cells decreased, and when the Onji extract of each individual extract was treated at concentrations of 50 and 100 μg / mL, the number of cells was greatly reduced. When treated with the extract, it was confirmed that the number of cells did not decrease regardless of the treatment concentration.

  When the results of each of the above-mentioned composite extracts (hot water extract, hot water extract and ethanol extract) were combined, it was found that the ethanol extract was most excellent in terms of fat accumulation inhibitory effect and cell safety.

In vivo anti-obesity effect of individual extracts and composite extracts of Sangpaxo, Kyo-Oh, Onji, and Sekisho From the results of Example 2, the results of Example 2 show that Sampaki, Kyo-Oh, Onji, and Sekisho have the effect of suppressing fat accumulation and cell safety in vitro. Since it was confirmed that the ethanol extract showed an excellent effect, it was confirmed whether or not the ethanol extract was effective even under in vivo conditions. For this purpose, the individual extract and the composite extract obtained by the ethanol extraction method were bred while feeding the mice, and the body weight, food intake and fat weight of the bred mice were measured, and liver tissue and kidney tissue were measured. Comparative analysis was performed.

Example 3-1: Acquisition of mice raised according to each condition 170 5-week-old male C57BL / 6N mice were purchased and allowed to acclimate for 1 week, and then 60% high fat diet (HFD) for 5 weeks. The fed mice were reared, then the reared mice were divided into 17 groups of 10 mice, and were fed with feeds of different conditions containing different test substances, and further reared for 6 weeks (Table 3). At this time, the positive control group was a group to which Xenical which is a known anti-obesity agent was administered, and the composite extract was divided into a normal diet group (1X) and an excess diet group (4X). The breeding room temperature is maintained at 22 ± 1 ° C., the humidity is maintained at 50 ± 5%, light and dark are adjusted at 12 hour intervals, and 10% high fat diet and 60% high fat diet are Purchased from and gave.

Example 3-2: Body weight evaluation The body weights of the 17 types of experimental group mice reared in Example 3-1 were measured and subjected to comparative analysis (FIG. 4). As shown in FIG. 4, it was confirmed that the experimental group in which the body weight decreased at the level closest to the normal control group was the experimental group 9 (Onji-4X group), and the experimental group in which the body weight was subsequently decreased was the experimental group. 15 (KIOM-2012Ob (2) -4X group) and 17 (KIOM-2012Ob (3) -4X group). It was found that the mice of the other experimental groups also showed lower levels than the negative control group and generally showed a weight loss effect.

  However, in experimental group 9 (Onji-4X group), 4 out of 10 animals died in 6 weeks, and 1 person was in a very deteriorated state of health, confirming the serious damage caused by toxicity. It was. In contrast, experimental group 15 (KIOM-2012Ob (2) -4X group) and 17 (KIOM-2012Ob (3) -4X group) showed no damage due to toxicity.

Example 3-3: Evaluation of food intake The food intake of 17 kinds of experimental group mice reared in Example 3-1 was measured and subjected to comparative analysis (FIG. 5). As shown in FIG. 5, although there was some difference in food intake for each experimental group, there was no significant difference except for experimental group 9 (Onji-4X group).

Example 3-4: Fat Weight Evaluation The 17 experimental group mice raised in Example 3-1 were fasted for 5 hours and induced to digest all the food ingested by the mice, and each mouse was cervical dislocation method. And then abdominal fat and subcutaneous fat were removed from each mouse. Abdominal fat and subcutaneous fat extracted as described above were washed with physiological saline, water was removed through filter paper, and then the total weight of these fats was measured for comparative analysis (FIG. 6). As shown in FIG. 6, it was confirmed that the fat weight was significantly reduced in the experimental group 9 (Onji-4X group) and the experimental group 15 (KIOM-2012Ob (2) -4X group) compared to the negative control group. . In addition, experimental group 12 (KIOM-2012Ob (1) -1X group), experimental group 14 (KIOM-2012Ob (2) -1X group) and experimental group 16 (KIOM-2012Ob (3 ) -1X group), fat weight increases in the order of experimental groups 14, 16 and 12, and experimental group 13 (KIOM-2012Ob (1) -4X group), experimental group 15 (KIOM-2012Ob (2)- 4X group) and experimental group 17 (KIOM-2012Ob (3) -4X group) were compared, it was confirmed that the fat weight increased in the order of experimental groups 15, 17 and 13. Therefore, in view of the contents of Sangaku, Kyo-Oh, Onji, and Seki-sho contained in each of the above-mentioned composite extracts, the ingredient that has the greatest influence on the fat increase inhibitory effect of the composite extract is Onji, followed by Kyo-o. In other words, it was analyzed that Japanese pepper has the least contribution to the effect of suppressing fat increase.

Example 3-5: Pathological Analysis of Liver Tissue The liver tissue was excised from the mouse sacrificed in Example 3-4, fixed with formalin for pathological analysis, and microscopically contained in the liver tissue. The bullous lipoma level and the chronic inflammation level were comparatively analyzed (FIG. 7). As shown in FIG. 7A, the minute bullous lipoma contained in the liver tissue contains Onji extract (experimental groups 8 and 9) and composite extract (experimental groups 12 to 17) compared to the negative control group. When administered, both values were low, confirming that the level of microvesicular lipoma contained in the liver tissue was significantly reduced.

  Further, as shown in FIG. 7B, the chronic inflammation level of the liver tissue is higher than that of the negative control group in all the experimental groups, and among them, the mice administered with Onji extract (experimental groups 8 and 9). Is the highest level. In contrast, mice administered with the composite extract (experimental groups 12 to 17) showed lower levels than mice administered with Onji extract.

Example 3-6: Pathological analysis of kidney tissue After removing the kidney tissue from the mouse sacrificed in Example 3-4 and fixing it with formalin, a pathological analysis is performed and it is contained in the kidney tissue. Chronic inflammation levels were compared and analyzed (Figure 8). As shown in FIG. 8, the chronic inflammation level of kidney tissue is higher in all experimental groups than in the negative control group as well as the normal control group, and among them, the mice administered with Onji extract (experimental group 9) It is a relatively high level. In contrast, mice administered with the composite extract (experimental groups 12 to 17) showed the same or lower levels as mice administered with the Onji extract.

  Summarizing the results of Examples 3-2 to 3-6, the Onji extract and the combined extract exhibit obesity-suppressing effects in vivo, and are excellent in obesity-suppressing effects, but are seriously toxic to animals. Compared to the above, it was found that the composite extract exhibits improved safety with a relatively excellent obesity-suppressing effect.

The obesity-suppressing effect of the compound extract derived from Sangpaxo, Kyo-Oh, and Onji From the results of Example 3-4, it was analyzed that the component contributing to the fat increase-inhibiting effect was the smallest among the components contained in the compound extract. It was confirmed whether the composite extract extracted from the sample which consists only of Sangpaxo, Kyo-Oh, and Onji shows an obesity suppression effect.

Example 4-1 Obtaining a natural extract Obtain a mixture that necessarily contains ground sampaxo, leopard, and onzi, and selectively include pebbles and clover (Table 4), add 300 mL of 25% ethanol to the mixture, 38 Each composite extract was obtained by extracting for 24 hours while maintaining at 0 ° C. Each extract obtained as described above was filtered to obtain a liquid component, and the obtained liquid component was freeze-dried to obtain a powdery extract. The powdery extract was dissolved in distilled water at a concentration of 100 mg / mL and used as a sample in later experiments.

  Moreover, the green tea extract used as a comparison group was obtained by the same method.

Example 4-2: Acquisition of Mice Breeding under Each Condition 126 5-week-old male C57BL / 6N mice were purchased and allowed to acclimate for 1 week, after which the mice were divided into 14 groups of 9 mice, 60% high fat Feeds of different conditions including test substances different from diet (HFD) were fed for 8 weeks (Table 5). At this time, the breeding room temperature was maintained at 22 ± 1 ° C., the humidity was maintained at 50 ± 5%, the light and dark were adjusted at 12-hour intervals, and physiological saline was used as an excipient.

Example 4-3: Body weight evaluation The body weights of the 14 types of experimental group mice raised in Example 4-2 were measured and subjected to comparative analysis (FIG. 9). As shown in FIG. 9, the weight of all the experimental groups (experimental groups 27 to 34) is lower than that of the negative control group, and the experimental group in which the weight is decreased at the level closest to the normal control group is the experimental group 34. (KSL), then experimental group 28 (K 300), experimental group 30 (KS 300), experimental group 33 (KCL), experimental group 29 (KS 150), experimental group 27 (K 150), experimental group 31 ( It was confirmed that the order was KC 150) and experimental group 32 (KC 300).

  From the above results, it was found that a composite extract extracted from a sample consisting of Sangpaxo, Kyo-Oh and Onji also showed a body weight suppression effect.

Example 4-4: Evaluation of food intake The food intake of 14 types of experimental group mice reared in Example 4-2 was measured and subjected to comparative analysis (FIG. 10). As shown in FIG. 10, there was some difference in food intake for each experimental group, but there was no significant difference.

Example 4-5: Fat Weight Evaluation The 14 types of experimental group mice reared in Example 4-2 were fasted for 5 hours, induced to digest all the food ingested by the mice, and each mouse was cervical dislocation method. And abdominal genital fat, mesenteric fat and subcutaneous fat were removed from each mouse. Abdominal genital fat, mesenteric fat and subcutaneous fat extracted as described above were washed with physiological saline, water was removed through filter paper, and then each weight and total weight of these fats were measured for comparative analysis ( Figures 11a-11d).

  As shown in FIG. 11a, in the abdominal genital fat, all the experimental groups (experimental groups 27 to 34) have lower levels than the negative control group, and the experimental group in which the fat weight decreases at the level closest to the normal control group is Experiment group 28 (K 300), then experiment group 34 (KSL), experiment group 30 (KS 300), experiment group 33 (KCL), experiment group 27 (K 150), experiment group 32 (KC 300), experiment It was confirmed that the order was group 29 (KS 150) and experimental group 31 (KC 150).

  As shown in FIG. 11b, in the mesenteric fat, all experimental groups (experimental groups 27 to 34) have a level lower than that of the negative control group, and the experimental group in which the fat weight decreases at a level closest to the normal control group. Are experimental group 30 (KS 300), then experimental group 34 (KSL), experimental group 28 (K 300), experimental group 33 (KCL), experimental group 32 (KC 300), experimental group 29 (KS 150), It was confirmed that the order was the experimental group 27 (K 150) and the experimental group 31 (KC 150).

  As shown in FIG. 11c, in the subcutaneous fat, the experimental group in which all the experimental groups (experimental groups 27 to 34) had a lower level than the negative control group and the fat weight decreased at the level closest to the normal control group was the experiment. Group 28 (K 300), then experiment group 34 (KSL), experiment group 30 (KS 300), experiment group 33 (KCL), experiment group 29 (KS 150), experiment group 27 (K 150), experiment group It was confirmed that the order was 32 (KC 300) and the experimental group 31 (KC 150).

  As shown in FIG. 11d, in the total fat, the experimental group in which all the experimental groups (experimental groups 27 to 34) had a lower level than the negative control group and the fat weight decreased at the level closest to the normal control group was the experiment. Group 28 (K 300), then experiment group 34 (KSL), experiment group 30 (KS 300), experiment group 33 (KCL), experiment group 27 (K 150), experiment group 29 (KS 150), experiment group It was confirmed that the order was 32 (KC 300) and the experimental group 31 (KC 150).

  When the results of FIGS. 11a to 11d were combined, it was found that the composite extract extracted from the sample consisting of Sangakuso, Kyoukou and Onji showed a fat accumulation inhibitory effect.

Example 4-6: Evaluation of Ghrelin Levels Ghrelin levels secreted from the stomach and known as hunger hormones were used in the 14 experimental groups of mice reared in Example 4-2. The evaluation was performed by subdividing into activated ghrelin, desacyl-ghrelin and ghrelin ratio.

  First, the active ghrelin level present in plasma was measured using a ghrelin assay kit (Active Ghrelin ELISA kit, SCETI, Japan). In general, blood from each experimental group of mice was mixed in a tube containing EDTA and aprotinin and then centrifuged to obtain plasma. A sample was prepared by adding 1 mol / L HCL corresponding to 10% of the plasma volume to the plasma. The sample was added to the ghrelin measurement kit for reaction, the absorbance at 450 nm was measured, and the activated ghrelin level was calculated from the measured absorbance value (FIG. 12a).

  As shown in FIG. 12a, in active ghrelin, the experimental group having a level higher than that of the negative control group is the experimental group 32 (KC 300), and the experimental group having a value similar to the negative control group is the experimental group. Group 27 (K 150) and experiment group 34 (KSL), the experimental groups having a level lower than that of the negative control group are experimental group 29 (KS 150), experimental group 28 (K 300), and experimental group 33 (KCL). Experiment group 30 (KS 300) and Experiment group 31 (KC 150), and it was confirmed that the experiment group with the lowest level was experiment group 29 (KS 150).

  Next, for the desacyl ghrelin level in plasma, use the desacyl-Ghrelin ELISA kit (SCETI, Japan) instead of the ghrelin assay kit (Active Ghrelin ELISA kit, SCETI, Japan). Except for, the measurement was carried out by the same method as described above (FIG. 12b).

  As shown in FIG. 12b, in desacyl ghrelin, the experimental group whose level is lower than the value of the negative control group is the experimental group 32 (KC 300), and the experimental group having the same value as that of the negative control group is the experimental group. Group 29 (KS 150) and experiment group 34 (KSL), and the experimental groups with higher levels than the negative control group were experimental group 27 (K 150), experimental group 28 (K 300), experimental group 33 (KCL) The experimental group 30 (KS 300) and the experimental group 31 (KC 150), and the experimental group having the highest level was confirmed to be the experimental group 33 (KCL).

  Finally, the ghrelin ratio was calculated as a percentage of the active ghrelin level relative to the measured desacyl ghrelin level (FIG. 12c).

  As shown in FIG. 12c, in the ghrelin ratio, the experimental group having a level higher than the value of the negative control group is the experimental group 32 (KC 300), and the experimental group having the same value as that of the negative control group is the experimental group. Experimental group 34 (K150), experimental group 29 (KS 150), experimental group 28 (K 300), experimental group 33 (KCL), which is group 27 (K 150) and has a level lower than that of the negative control group Experimental group 30 (KS 300) and Experimental group 31 (KC 150), and it was confirmed that the experimental group with the lowest level was experimental group 33 (KCL).

  Combining the results of FIGS. 12a-12c, the combined extract extracted from the sample consisting of Sangaku, Kyo-Oh and Onji has a ratio of active ghrelin, desacyl ghrelin and ghrelin at a level similar to or lower than that of the negative control group. As shown, it was found that the obesity-suppressing effect of the composite extract does not appear due to suppression of appetite.

Example 4-7: Leptin Level Evaluation The leptin level in plasma was evaluated for the 14 experimental mice raised in Example 4-2.

  Specifically, leptin present in plasma was measured using a leptin measurement kit (Mouse and Rat Leptin ELISA kit, mediagnost, Germany). In general, blood obtained from mice in each experimental group was mixed in a tube containing EDTA and aprotinin, and then centrifuged to obtain plasma. The plasma is diluted by adding the dilution buffer contained in the kit, then the diluted solution is added to the leptin measurement kit and reacted, the absorbance at 450 nm is measured, and the leptin level is determined from the measured absorbance value. Was calculated (FIG. 13).

  As shown in FIG. 13, the leptin level in plasma is lower than the negative control group in all experimental groups (experimental groups 27 to 34), and the leptin level in plasma decreases at the level closest to the normal control group. The experimental group to be performed is the experimental group 28 (K 300), followed by the experimental group 33 (KCL), the experimental group 34 (KSL), the experimental group 30 (KS 300), the experimental group 29 (KS 150), and the experimental group 27 (K 150), experiment group 32 (KC 300), and experiment group 31 (KC 150).

  In general, it is known that in laboratory animals in which obesity has been induced, the leptin level in blood increases as leptin resistance increases. It was confirmed that the experimental group 28 (K 300) administered with the composite extract extracted from the sample of Sangaku, Kyou-o and Onji provided by the present invention had the lowest leptin level, which is the most resistant to leptin. Since it means a low level, it was found that the composite extract has an effect of effectively suppressing the occurrence of obesity.

Example 4-8: Evaluation of blood component levels Blood neutral fat, total cholesterol, LDL cholesterol, HDL cholesterol, blood glucose according to a known method for the 14 types of experimental group mice reared in Example 4-2 The levels of blood components such as creatinine, urea, LDH, ALP, GPT, GOT were evaluated (FIGS. 14a to 14k).

  As shown in FIG. 14a, in blood triglyceride, only the experimental group 34 (KSL) is at a level lower than the value of the negative control group, and the other experimental groups have the same level as that of the negative control group. Alternatively, it was confirmed that the experimental group having the highest level was the experimental group 32 (KC 300).

  As shown in FIG. 14b, in the total cholesterol in blood, the experimental groups whose level is lower than the value of the negative control group are the experimental group 27 (K 150) and the experimental group 34 (KSL), and the negative control group Experimental groups 28 (K 300) and 30 (KS 300) have values similar to the values of the experimental group 29, the experimental group 29 (KS 150) and the experimental group having a level higher than that of the negative control group. Group 33 (KCL), experiment group 32 (KC 300), and experiment group 31 (KC 150), and it was confirmed that the experiment group with the highest level was experiment group 33 (KCL).

  As shown in FIG. 14c, in the blood LDL cholesterol, the experimental groups whose levels are higher than the value of the negative control group are the experimental group 31 (KC 150), the experimental group 32 (KC 300), and the experimental group 33 (KCL). Experimental groups 29 (KS 150) and 30 (KS 300) have the same value as that of the negative control group, and the experimental group 27 (K) has a lower level than that of the negative control group. 150), experimental group 28 (K300) and experimental group 34 (KSL), and it was confirmed that the lowest experimental group was experimental group 34 (KSL).

  As shown in FIG. 14d, in the blood HDL cholesterol, only the experimental group 28 (K300) has a level lower than the value of the negative control group, and the other experimental groups have the same level as or higher than the value of the negative control group. The highest experimental group was confirmed to be experimental group 31 (KC 150).

  As shown in FIG. 14e, in glucose, the experimental groups whose levels are lower than the values of the negative control group are the experimental group 28 (K 300) and the experimental group 29 (KS 150). The experimental group having the same value is the experimental group 34 (KSL), and the experimental group having a level higher than that of the negative control group is the experimental group 27 (K 150), the experimental group 31 (KC 150), and the experimental group 32 (KC). 300), experiment group 33 (KCL) and experiment group 30 (KS 300), and it was confirmed that the experiment group with the highest level was experiment group 32 (KC 300).

  As shown in FIG. 14f, in blood creatinine, all experimental groups (experimental groups 27 to 34) are at the same level or higher than the negative control group, but at the same level as the negative control group. The experimental groups are experimental group 29 (KS 150) and experimental group 31 (KC 150), all other experimental groups are at a level higher than the value of the negative control group, and the highest level experimental group is experimental group 34 ( KSL).

  As shown in FIG. 14g, in the blood urea (urea), all the experimental groups (experimental groups 27 to 34) had a level higher than that of the negative control group, but the urea level increased to the highest level. The group is experimental group 33 (KCL), followed by experimental group 30 (KS 300), experimental group 34 (KSL), experimental group 27 (K 150), experimental group 31 (KC 150), experimental group 28 (K 300). It was confirmed that the experimental group 29 (KS 150) and the experimental group 32 (KC 300) were in this order.

  As shown in FIG. 14h, in blood LDH (lactate dehydrogenase), all the experimental groups (experimental groups 27 to 34) have the same or higher level as the negative control group, but the same level as the negative control group. The experimental groups are experimental group 30 (KS 300) and experimental group 34 (KSL), and all other experimental groups are at a level higher than the value of the negative control group, and the experimental group with the highest level is experimental group 32 ( KC 300).

  As shown in FIG. 14i, in blood ALP (alkaline phosphatase), only the experimental group 29 (KS 150) has a higher level than the value of the negative control group, and the other experimental groups have the same level as that of the negative control group. Alternatively, it was confirmed that the experiment group 31 (KC 150) was the lowest level.

  As shown in FIG. 14j, in the blood GPT (glutamic-pyruvic transaminase), all the experimental groups (experimental groups 27 to 34) are at the same level or higher than the negative control group, but at the same level as the negative control group. The experimental groups at the level of are the experimental group 27 (K 150), the experimental group 28 (K 300) and the experimental group 30 (KS 300), and the other experimental groups are all higher than the value of the negative control group, The highest level experimental group was identified as experimental group 31 (KC 150).

  As shown in FIG. 14k, in blood GOT (glutamic-oxaloacetic transaminase), all the experimental groups (experimental groups 27 to 34) are at the same level or higher than the negative control group, but at the same level as the negative control group. The experimental group of the level is experimental group 29 (KS 150) and experimental group 34 (KSL), all other experimental groups are higher than the value of the negative control group, the highest level experimental group is the experiment It was confirmed to be Group 31 (KC 150).

  As shown in FIGS. 14i to 14k, the blood ALP, GPT and GOT levels of the experimental group administered with the composite extract extracted from the sample of Sangakuso, Kyoukou and Onji provided by the present invention are generally compared with those of the control group. The composite extract is analyzed as not exhibiting hepatotoxicity.

Claims (14)

A pharmaceutical composition for the prevention or treatment of obesity comprising a combined extract of sanpaxo, kyou-o and onji or a fraction thereof , wherein the combined extract uses a C1-C4 alcohol or a mixed solvent of the alcohol and water A pharmaceutical composition which is an extract .   2. The pharmaceutical according to claim 1, wherein the composite extract is an extract of a sample in which saxophone, kyoto, and onji are mixed at a ratio of 1: 0.2 to 1: 0.2 to 1 (w / w / w). Composition. Prevention or prevention of obesity comprising a composite extract of a sample in which sampaxo, kyou-oh, onji, and ginger are mixed at a ratio of 10: 4 to 6: 10: 4 to 6 (w / w / w / w) or a fraction thereof A pharmaceutical composition for treatment , wherein the composite extract is an extract using a C1-C4 alcohol or a mixed solvent of the alcohol and water . The combined extracts are pharmaceutical composition according to claim 1 or 3 is obtained by extracting with 25% ethanol (EtOH) It said fraction has the combined extracts solvent fractionation method, ultrafiltration fractionation, fractionation product was fractionated by applying a method selected from the group consisting of chromatographic fractionation, and combinations thereof The pharmaceutical composition according to claim 1 or 3. A food composition for prevention or amelioration of obesity comprising a combined extract of sanpaxo, kyou-o and onji or a fraction thereof , wherein the combined extract uses a C1-C4 alcohol or a mixed solvent of the alcohol and water. A food composition that is an extract .   The composite extract is an extract of a sample obtained by mixing Sampaki, Kyo-o and Onji at a ratio of 1: 0.2 to 1: 0.2 to 1 (w / w / w). Composition. Prevention or prevention of obesity comprising a composite extract of a sample in which sampaxo, kyou-oh, onji, and ginger are mixed at a ratio of 10: 4 to 6: 10: 4 to 6 (w / w / w / w) or a fraction thereof A food composition for improvement , wherein the composite extract is an extract using a C1-C4 alcohol or a mixed solvent of the alcohol and water . The combined extracts are food composition according to claim 6 or 8 is obtained by extracting with 25% ethanol (EtOH). It said fraction has the combined extracts solvent fractionation method, ultrafiltration fractionation, fractionation product was fractionated by applying a method selected from the group consisting of chromatographic fractionation, and combinations thereof The food composition according to claim 6 or 8. The manufacturing method of the composition of Claim 1 or 6 including the step which acquires the sample by extracting the sample containing a saxophone, Kyo-Oh, and Onji with C1- C4 alcohol or the mixed solvent of the alcohol and water .   The manufacturing method according to claim 11, wherein the sample contains Sangpaxo, Kyo-Oh and Onji at a ratio of 1: 0.2 to 1: 0.2 to 1 (w / w / w). A sample containing Sangpaxo, Kyo-Oh, Onji, and Sekisho at a ratio of 10: 4 to 6: 10: 4 to 6 (w / w / w / w) is a C1- C4 alcohol or a mixed solvent of the alcohol and water. The manufacturing method of the composition of Claim 3 or 8 including the step which extracts and acquires an extract.   A method for treating obesity, comprising the step of administering the pharmaceutical composition according to any one of claims 1 to 5 to an individual other than a human.