KR20170024700A

KR20170024700A - Composition for treatment, improvement or prevention of obesity, Diabetes or nonalcoholic fatty liver disease comprising extract of fruit of Sorbus commixta as an effective component

Info

Publication number: KR20170024700A
Application number: KR1020150120029A
Authority: KR
Inventors: 나천수; 나대승; 김진범
Original assignee: 주식회사 큐어싸이언스; 농업회사법인 주식회사 생명의나무
Priority date: 2015-08-26
Filing date: 2015-08-26
Publication date: 2017-03-08
Also published as: KR101811210B1

Abstract

The present invention relates to a composition for treating, improving or preventing obesity, diabetes or non-alcoholic fatty liver diseases, comprising an extract of Sorbus commixta fruit as active ingredients. More specifically, the extract of Sorbus commixta fruit exhibits effects related to inhibiting diabetes such as neutral fat-decomposition ability, a fat tissue weight reduction, blood component control ability, fat cell differentiation gene control ability, and is capable of regulating ALT, AST, and TG values in the liver. The present invention relates to the composition for treating, improving or preventing obesity, diabetes or nonalcoholic fatty liver diseases, comprising the extract of Sorbus commixta fruit as the active ingredients.

Description

TECHNICAL FIELD The present invention relates to a composition for treating, ameliorating or preventing obesity, diabetic or non-alcoholic fatty liver disease, which comprises extracts of R. acidophilus as an active ingredient. component}

The present invention relates to a pharmaceutical composition for treating or preventing obesity, diabetes or non-alcoholic fatty liver disease, or a health functional food composition for improving or preventing obesity or non-alcoholic fatty liver disease.

Obesity is a chronic disease that increases the morbidity and mortality of various diseases due to excessive accumulation of adipose tissue due to abnormality of energy balance control function or overeating. Obesity can act as a cause of diseases such as hypertension, hyperlipemia and cardiovascular disease or diabetes as well as problems with obesity itself, and about 80% of obese patients have the same diseases (Mantzoros et < RTI ID = 0.0 > al ., J Clin Endocrinol Metab 2000; 85: 4000-2), and about 300,000 deaths annually from obesity have been reported (Allison et < RTI ID = al ., JAMA 1999; 282: 1530-8). An increase of 1 kg in weight increases the risk of cardiovascular disease by 3.1%, the risk of diabetes by 4.5-9%, and the decrease of about 11% in body weight is known to reduce the mortality rate by 25% (Arbeeny et < RTI ID = 0.0 > al . , Obes Res 2004; 12: 1191-6).

In 1893, thyroid hormones were used to treat obesity, using the adrenergic and adrenaline-accelerated thyroid hormones, but these drugs accelerated the loss of lean tissue mass rather than reducing fat tissue It causes negative nitriogen balance and causes side effects such as cardiac toxicity. Therefore, it is used only when hypothyroidism is present. In the 1930s, amphetamine, which has mainly an appetite suppressing effect, was used. However, since it is drug dependent, it is not allowed to be administered for a long time, and phentermine, diethylpropion and fenfluramine It has been used in obese patients, but most treatments have been banned for heart disease and mental illnesses such as hypertension, arrhythmia, pemphigus hypertension, memory impairment.

Currently, development strategies for obesity drugs include appetite suppressants that stimulate central adrenergic receptors, inhibit serotonin reuptake, adrenergic beta 3 agonists, heat metabolism accelerators, digestion inhibitors that inhibit the activity of lipases, and leptin ), And hormone modulators such as PYY (Dunstan et al . , Nature reviews drug discovery 2006; 5: 919-931). Orlistat, a dual lipase inhibitor, and sibutramine, which inhibits serotonin reuptake and cause appetite suppression, are prescribed by the Food and Drug Administration (FDA), but have adverse effects such as fat, headache, and elevated blood pressure , It is still not easy to develop drugs that have both stability and efficacy.

On the other hand, various plant extracts have been utilized to develop a therapeutic agent for obesity, and they are actively under investigation. Therefore, interest in the treatment of obesity using plant extracts, which have not been developed until now, is increasing.

Especially, it is known that the leaves of the fallen leaves that are native to Ulleungdo, Jeju Island, and Gangwon Province in Korea are rich in vitamin C, flavonoids, catechins, carotene, sugars and amino acids in their fruits. However, However, most of them are not harvested without being processed, and they are left in the mountains and are only responsible for breeding seeds by nature. However, there is a problem that they are not actively applied industrially.

Korea Patent Publication No. 2014-0032645 Korean Patent No. 0973195

The present invention has been made in view of the above-mentioned problems, and an object of the present invention is to provide a pharmaceutical composition for treating or preventing obesity, diabetes or non-alcoholic fatty liver disease using Rake extract.

Another object of the present invention is to provide a health functional food composition for improving or preventing obesity, diabetic or non-alcoholic fatty liver by using the extract of R. melanogaster.

One aspect of the present invention relates to a pharmaceutical composition for treating or preventing obesity, diabetic or non-alcoholic fatty liver disease, which comprises extracts of Raspberry Fruit as an active ingredient.

Another aspect of the present invention relates to a health functional food composition for improving or preventing obesity, diabetic or non-alcoholic fatty liver disease, which comprises an extract of Aspergillus oryzae as an active ingredient.

According to the present invention, it is possible to provide a method for preventing or treating obesity, treatment, improvement or prevention of obesity, which is useful in the fields of pharmacy and food for the prevention of obesity, treatment, improvement, or prevention because of its excellent ability to control triglyceride resolution, weight loss of fat tissue, have. In addition, the extracts of R. acidophilus can control the levels of ALT, AST and TG in the liver, and thus can be usefully used in the field of pharmacy and food for the treatment, improvement or prevention of nonalcoholic fatty liver disease.

FIG. 1 is a graph showing the effect of resolving triglyceride fat in adipocytes according to a sample, including Raspberry Extract and Raspberry Extract.
FIG. 2 is a graph showing an evaluation of the obesity-inhibiting effect induced by the high-fat diet of Raspberry fruit.
FIG. 3 is a graph showing the effect of hydrothermal extract of R. melanogaster on control of adipocyte differentiation regulation gene.
FIG. 4 is a graph showing a change in body weight of a manganese fruit juice extract obtained from a high fat diet-induced obesity-induced mouse.
FIG. 5 is a graph showing the effect of inhibiting the accumulation of abdominal fat in the obese-induced mice by the high-fat diet method.
FIG. 6 is a graph showing changes in the concentration of adiponectin and leptin in the blood by the extract of Rana cinctice.
Fig. 7 shows the result of histological analysis of adipocytes in high fat diet-induced obesity-induced mice by the extract of R. melanogaster.
FIG. 8 is a graph showing ALT and AST changes in the blood of a high fat diet-induced obesity-induced mouse caused by the Raspberry fruit extract.
FIG. 9 is a graph showing triglyceride (TG) changes in the blood of a high fat diet-induced obesity-induced mouse caused by R. melanogaster extract.
FIG. 10 is a graph showing antidiabetic activity of the Raspberry extract.

Hereinafter, the present invention will be described in more detail with reference to the drawings.

According to one embodiment, the Rectum fruit extract may be an extract of water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof.

According to another embodiment, the extract may be ethyl acetate, hexane or toluene fractions of water, an alcohol having 1 to 4 carbon atoms or an extract of a mixed solvent thereof.

As used herein, the term " comprising as an active ingredient " is meant to include an amount sufficient to treat or prevent obesity, diabetes or non-alcoholic fatty liver disease. The pharmaceutical composition for treating or preventing obesity, diabetes mellitus or non-alcoholic fatty liver disease according to the present invention is preferably, but not limited to, 0.1 to 50% by weight of an extract of Momordica officinalis based on the total weight of the composition.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of medicaments.

The composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., oral preparations, suppositories and sterilized injection solutions according to a conventional method have. Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may be formulated into the compositions of the present invention with at least one excipient such as starch, calcium carbonate, (sucrose), lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As a suppository base, witepsol, macrogol, tween 61, cacao paper, laurin, glycerol gelatin and the like can be used.

The composition of the present invention may be administered orally or parenterally, and any parenteral administration method may be used, and systemic administration or topical administration is possible, but systemic administration is more preferable, and intravenous administration is most preferable.

The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the composition of the present invention is preferably administered at 0.0001 to 0.03 g / kg per day, preferably 0.001 to 8 mg / kg per day. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.

According to one embodiment, the Rectum fruit extract may be an extract of water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof. Again, the above extract may be a hot-water extract.

In the health functional food composition, the kind of the food is not particularly limited. Examples of foods to which the above substances can be added include dairy products including dairy products, meat, sausage, bread, biscuits, rice cakes, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, Beverages, alcoholic beverages and vitamin complexes, dairy products, and dairy products, all of which include health functional foods in a conventional sense.

The Rectum fruit extract of the present invention can be added directly to food or used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (for prevention or improvement). Generally, the amount of the compound in the health food may be 0.1 to 90 parts by weight of the total food. However, in the case of long-term intake intended for health and hygiene purposes or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

In the case of producing a beverage, there is no particular limitation on other ingredients other than the above-mentioned Aspergillus oryzae extract as an essential ingredient at the indicated ratio, and it may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 of the composition of the present invention.

In addition to the above, the Raspberry fruit extract can be used as a flavoring agent such as a variety of nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate etc.), pectic acid and its salts, , Organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, Raspberry fruit extract may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks.

These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the Raspberry fruit extract.

Example

Hereinafter, the present invention will be described in more detail with reference to Examples and the like, but the scope and content of the present invention can not be construed to be limited or limited by the following Examples. In addition, it is apparent that, based on the teachings of the present invention including the following examples, those skilled in the art can easily carry out the present invention in which experimental results are not specifically shown.

Production Example 1: Preparation of ethanol extract of green tea

33.2 kg of Rowanberry fruit was extracted with ethanol for 3 days at room temperature, and the extract was concentrated under reduced pressure to obtain a solid content of 266.668 g.

Production Example 2: Preparation of hot water extract

After adding 996 kg of water to 33.2 kg of Raspberries, the mixture was subjected to hot extraction at 100 ° C. for 3 hours. The filtrate was concentrated under reduced pressure to 60 mmHg to obtain Raspberry extract.

Production Examples 3 to 5: Preparation of fractions of Fusarium exudate extract

241.03 g of the Fusarium exarqueum extract of Preparation Example 1 was fractionated successively using ethyl acetate, hexane and toluene. Each fraction was concentrated under reduced pressure to obtain 30.653 g of the ethyl acetate fraction (Preparation Example 3), 51.663 g of the hexane fraction (Preparation Example 4), and 51.663 g of the toluene fraction (Preparation Example 5).

Experimental Example 1: Selection of anti-obesity functional materials

The selected efficacy of anti - obesity functional materials was investigated in order to select the extracts which can be used as anti - obesity functional materials among 31 forest plant resource extracts.

Anti-obesity efficacy screening was carried out on 31T3-L1 adipocytes differentiated for anti-obesity study through 31 forest plant resource extracts.

When 3 kinds of extracts of 3T3-L1 differentiated into adipocytes were treated for 24 hours (50 ~ 500 ug / ml), each extract induced the degradation of accumulated triglycerides or the glycerol release The results are shown in Table 1. The cultures were incubated with DMEM (glucose 1 g / liter Wel GENE Inc.) containing 20% fetal bovine serum (Wel GENE Inc., Korea) and 0.5% antibiotic (streptomycin / penicillin) , 5% CO ₂ for 24 hours.

Table 1 shows the results of selection efficacy evaluation of functional ingredients of anti-obesity functional materials of 31 kinds of forest plant resources. It was shown that the mungbean fruits among 31 extracts decompose triglyceride from adipocytes and increase the amount of glycerol produced as a culture medium. These results were similar to those of forskolin, which was used as a positive control.

Experimental Example 2: Evaluation of neutral lipid degradation ability of adipocyte fractions in adipocytes

Free Glycerol was evaluated from the adipocyte supernatant treated with fractions in the following manner in order to evaluate the neutral lipid resolving ability of adipocyte fractions in adipocytes.

The adipocytes (3T3-L1 adipocyte) differentiated for 8 days were cultured. The cultures were incubated with DMEM (glucose 1 g / liter Wel GENE Inc.) containing 20% fetal bovine serum (Wel GENE Inc., Korea) and 0.5% antibiotic (streptomycin / penicillin) , 5% CO ₂ for 24 hours. After culturing, the culture solution was removed and washed once with PBS (Phosphate buffer saline).

Each sample was prepared at a concentration as shown in Table 2, and the adipocyte was cultured in DMEM supplemented with 20% fetal bovine serum (Wel GENE Inc., Korea) and 0.5% antibiotic (streptomycin / penicillin) 1 g / liter Wel GENE Inc.) for 24 hours at 37 ° C and 5% CO ₂ . Thereafter, the supernatant was obtained, the pellet was removed by centrifugation, 0.1 ml of the culture solution and 0.1 ml of the glycerol reaction product were added, and the mixture was reacted at room temperature for 10 minutes.

sample Concentration (占 퐉 / ml) Sc- (fruit) - - 10 - 50 100 500 Sc- (bark) - - 10 - 50 100 500 Sc-Hex - - - 20 50 100 - Sc-Tol - - - 20 50 100 - Sc-EA - - - 20 50 100 - Sc-Res - - - - 50 100 500 Garcinia cambogia bark extract - - 10 - 50 100 500 Forskolin 4 8 - - - - -

O.D. Absorbance was measured at 570 nm and a standard curve was drawn with a standard glycerol solution, and the amount of free glycerol was quantified by substituting the absorbance of the test group.

FIG. 1 is a graph showing the effect of the decomposition of triglyceride fat in adipocytes according to the samples including the extracts of Rana corn fruit and Rana bark extract, Scarlet fruit (Sc- (fruit)); Raspberry extract (Sc- (bark)); Hexane fraction (Sc-Hex) of Raspberry Extract; Toluene fraction (Sc-Tol) of Raspberry Extract; Ethyl acetate fraction (Sc-EA) of Raspberry Extract; Residues of Raspberry Extract (Sc-Res); Garcinia cambogia bark extract (Garcinia cambogia); (3T3-L1 adipocyte) with various concentrations as shown in Table 2 above. The Garcinia cambogia bark extract (Garcinia cambogia); And forskolin were used as positive control.

1, it can be seen that the glycerol secretion is significantly increased in the ethyl acetate fraction (Sc-EA), the hexane fraction (Sc-Hex) and the toluene fraction (Sc-Tol) of the Rumex fruit extract, , The ethyl acetate fraction (Sc-EA), the hexane fraction (Sc-Hex) and the toluene fraction (Sc-Tol).

Experimental Example 4: Animal experiment

Seven week old male ICR mice were obtained from Central Lab. Animal Inc., Korea and selected as an experimental animal. Experiments were carried out using the hot-water extract of R. melanogaster prepared in Preparation Example 2.

The mice were obese by the high fat diet and the high fat diet was 60% kcal, containing 34% fat.

4-1: Weight change of adipose tissue by hot water extract

Seven-week-old male ICR mice were fed a high fat diet (High Fat Diet, HFD, 60% kcal, containing 34% fat) for 1 week and then administered orally once daily for 4 weeks. The samples used were ND (Normal Chow Diet), HFD (High Fat Diet), samples (Sc200, Sc500) and HCA (Hydroxycitric acid) At this time, the 60% high fat diet means that the calories (kcal) are 60% higher than the ND.

From the mice, subcutaneous aipose tissue (Sc AT), epididymal adipose tissue (Ep AT), mesenteric adipose tissue (Me AT) and retroperitoneal adipose tissue Re AT) were weighed and the weight of each adipose tissue was compared according to the sample.

As a result, as shown in FIG. 2, when the hydrothermal extract of R. bryozoa was administered, the weight of each adipose tissue was decreased.

4-2: Analysis of blood component changes by hot water extract

As shown in Table 3, the levels of TCHO, LDL-C, ALT, AST and Glucose were lower than those of obese mice, and TG and HDL-C did not change. It is shown that the extract of fruit juice extract has an effect of inhibiting obesity.

Blood component
(mg / dl) ND HFD Sc200 Sc500 HCA TCHO (mg / dl) 178.1 ± 14.76 237.2 ± 45.8 485.8 ± 24.5 184.2 ± 19.4 219.6 ± 36.3 TG (mg / dl) 152 ± 25.3 135.1 ± 27.4 153.8 ± 34.9 117.7 ± 24.8 112.7 ± 33.5 LDL-C (mg / dl) 38.8 ± 15.4 99.5 + 49.9 53.4 ± 20.6 51 ± 19.9 80.5 ± 31.7 HDL-C (mg / dl) 108.9 ± 1.52 108.8 ± 3.79 110 ± 0 109.6 ± 1 108.3 ± 5.38 ALT (U / L) 25.2 ± 5.1 39.6 ± 16.7 18.6 ± 3.4 19.5 ± 5.8 22.6 ± 6.9 AST (U / L) 72.7 ± 12 121 ± 42.5 83.6 ± 19.2 77.7 ± 28.7 118.8 ± 42.7 Glucose (mg / dl) 161.6 ± 44.2 269.2 ± 40 212.3 ± 31.9 215.8 ± 22.6 253 ± 22.4

TCHO: Total cholesterol

TG: Triglyceride

LDL-C: low density lipoprotein cholesterol

HDL-C: high density lipoprotein cholesterol

ALT: alanine transaminase (SGPT)

AST: aspartate tansaminase (SGOT)

4-3: Assessment of regulatory ability of adipocyte differentiation regulator of hot-water extract

Differentiation was induced by treating the cells with 50 μg / ml of Rice bran extract (Sc 50) during a series of steps to differentiate preadipocytes into adipocytes. At this time, Garcinia cambogia bark extract and phoscholine were used as positive control groups. The Garcinia cambogia bark extract was used at a concentration of 50 μg / ml and 100 μg / ml (Garcinia cambogia 50, Garcinia cambogia 100) and the phoscholine was used at a concentration of 4 μg / ml and 8 μg / ml (Forskolin 4, Forskolin 8).

RNA was extracted from mature adipocytes and total mRNA was quantified to synthesize cDNA. The gene expression of PPARγ (Peroxisome proliferator-activated receptor gamma) was confirmed by real-time PCR.

FIG. 3 is a graph showing the effect of hydrothermal extract of R. melanogaster on control of adipocyte differentiation regulation gene.

As shown in FIG. 3, the expression of PPARγ increases as pre-adipocytes differentiate into adipocytes, and 50 μg / ml of Scutellaria baicalensis extract (Sc 50) Lt; RTI ID = 0.0 > PPARs < / RTI > at early stages of adipogenic differentiation.

From these results, it can be seen that the extract of R. cornifolia can be used as a functional substance capable of inhibiting lipid synthesis and fat accumulation by controlling adipocyte differentiation.

4-4: Weight change of mouse by Fruit extract

Test wands were set up as shown in Table 4 for 7-week-old male ICR mice.

Test section sample Group 1 Normal Normal diet + PBS treatment Group 2 HFD 60% high fat diet + PBS treatment Group 3 HFD + Sc 500 60% highland method + rice bran fruit hot water extract 500mg / kg Group 4 HFD + fenofibrate 60% high fat diet + fenofibrate (positive control)

The number of individuals in each test group was 7, and the body weight was measured weekly while the high fat diet (60% kcal, containing 34% fat) was fed for 1 week and the samples of each test group were orally administered once a day for 4 weeks continuously.

FIG. 4 is a graph showing a change in body weight of a manganese fruit juice extract obtained from a high fat diet-induced obesity-induced mouse.

4, at the end of the experiment, the effect of suppressing weight gain by administering the hot water extract of Lycopersicon esculentum can be observed. In addition, since the effect of suppressing weight gain is observed from the first week after the oral administration is started, it can be seen that the effect of suppressing weight gain is relatively early.

As a result, it was possible to inhibit weight gain due to high fat diet and to inhibit from the early stage of diet by administering the extract of Araliaceae.

4-5: Suppression of abdominal fat festival by Raspberry Extract

Seven Lt. male ICR mice were fed diets for 5 weeks with normal diet, high fat diet (HFD), rice bran extract (Sc 500, 500 mg / kg) and Fenofibrate (positive control) (mesenteric adipose tissue) were measured.

FIG. 5 is a graph showing the effect of inhibiting the accumulation of abdominal fat in the obese-induced mice by the high-fat diet method.

Referring to FIG. 5, it can be seen that the group administered with Scutellaria fruit extract (Sc 500) showed an inhibitory effect on abdominal fat accumulation.

From these results, it can be seen that the extracts of R. melanogaster are effective in reducing the abdominal fat rather than the abdominal cavity.

4-6: Changes of adiponectin and leptin in the blood by the extract of Rana Ficus

The concentration of adiponectin and leptin in the blood is an important measure of obesity. Adiponectin (adiponectin) is a gonadotropin-releasing protein that is specifically secreted in adipocytes. Leptin (leptin) is a hormone that keeps the body fat that is secreted from adipose tissue constant, and the blood concentration increases with obesity.

Seven week old male ICR mice were fed a high fat diet (60 kcal, containing 34% fat) for 1 week and then administered orally once daily for 4 weeks. The samples used were ND (Normal Chow Diet), HFD (High Fat Diet), samples (Sc200, Sc500) and HCA (Hydroxycitric acid)

FIG. 6 is a graph showing changes in the concentration of adiponectin and leptin in the blood by the extract of Rana cinctice.

Referring to FIG. 6, it can be seen that the extract of Lycopersicon esculentum increases the concentration of adiponectin in the blood and decreases the concentration of leptin, which is effective for suppressing obesity.

4-7: Morphological changes of adipocyte by Fruit extract

Seven week old male ICR mice were fed a high fat diet (60 kcal, containing 34% fat) for 1 week and then administered orally once daily for 4 weeks. The samples used were ND (Normal Chow Diet), HFD (High Fat Diet), samples in which the extracts of Scutellaria baicalensis (Sc200, Sc500, Sc1000) and HCA (Hydroxycitric acid)

Histological analysis was performed on the subcutaneous aipose tissue (Sc AT) and epididymal adipose tissue (Ep AT) of the mouse to observe adipocytes.

Fig. 7 shows the result of histological analysis of adipocytes in a high fat diet-induced obesity-induced mouse by the extract of R. melanogaster.

Referring to Fig. 7, when the adipocyte is enlarged due to the finishing fruit extract Can be prevented.

4-8: Changes in ALT, AST and TG in blood caused by Fruit extract

Seven week old male ICR mice were fed a high fat diet (60 kcal, containing 34% fat) for 1 week and then administered orally once daily for 4 weeks. The samples used were ND (Normal Chow Diet), HFD (High Fat Diet), Scanned samples (Sc200, Sc500) and HCA (Hydroxycitric acid) control group.

The blood of the mouse was analyzed to analyze the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride (TG).

FIG. 8 is a graph showing ALT and AST changes in the blood of a high fat diet-induced obesity-induced mouse caused by the Raspberry fruit extract.

Referring to FIG. 8, it can be seen that, in the case of mice fed the extract of Araliaceae, the levels of ALT and AST in the blood are reduced, and thus it is effective in improving non-alcoholic fatty liver.

FIG. 9 is a graph showing triglyceride (TG) changes in the blood of a high fat diet-induced obesity-induced mouse caused by R. melanogaster extract.

Referring to FIG. 9, it can be seen that mice having a diet of Fusarium oxysporum are effective in reducing obesity by decreasing the level of TG in the blood.

Experimental Example 5: Animal Experiment - Observation of blood glucose (glucose)

5-1: Changes in blood glucose level after administration of Fusarium oxysporum

Seven week old male ICR mice were obtained from Central Lab. Were purchased from Animal Inc., Korea and selected as experimental animals.

(NONE), Alloxan (Alloxan), which is a diabetic induction model inducing diabetes by Alloxan, Alloxan, and Alloxan were administered to the experimental group (Example 1) and the Alloxan administration group Blood glucose was measured on the day of Alloxan administration (0day), 3 days, 6 days and 9 days, respectively, and the results are shown in FIG. 10, using the test group administered with the hot water extract of Lycopersicon esculentum of Preparation Example 2 .

Experimental group sample Normal control group NONE Normal diet + PBS treatment Alloxan administration group Alloxan 60% high fat diet + PBS treatment Experimental group of hot water extract rowan The extract of Rana bovis extract of Preparation Example 2 Experimental group of ethanol extract of Rana bovis Rowan EA The extract of Rana bovis ethanol extract of Preparation Example 1

As a result, as shown in FIG. 10, it was confirmed that all of the extracts of R. melanogaster and R. melanogaster prepared in Preparation Example 1 and Preparation Example 2 exhibited antidiabetic activity against the test group of Alloxan, The antidiabetic activity of the ethanol extract of Rana bovis from Preparation Example 1 was higher.

5-2: Toxicity experiment

The 7-week-old male ICR mice were treated with 1 mg / mouse of Wakoobu fruit extract and Wakamatsu berry extract prepared in Preparation Example 1 and 2, respectively, once a day for a total of 5 days, .

&Lt; Formulation Example 1 > Preparation of pharmaceutical preparation

1-1. Manufacture of Powder

500 mg of the ethyl acetate fraction of Preparation Example 3

Lactose 100 mg

10 mg of talc

The above components are mixed and filled in airtight bags to prepare powders.

1-2. Manufacture of tablets

500 mg of the ethyl acetate fraction of Preparation Example 3

Corn starch 100 mg

Lactose 100 mg

2 mg of magnesium stearate

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

1-3. Manufacture of capsules

500 mg of the ethyl acetate fraction of Preparation Example 3

Corn starch 100 mg

Lactose 100 mg

2 mg of magnesium stearate

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

1-4. Injection preparation

500 mg of the ethyl acetate fraction of Preparation Example 3

Sterile sterilized water for injection

pH adjuster

(2 ml) per ampoule in accordance with the usual injection method.

1-5. Manufacture of liquid agent

100 mg of the ethyl acetate fraction of Preparation Example 3

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, The liquid is prepared by sterilization.

&Lt; Formulation Example 2 > Preparation of health functional food (powder type)

1000 mg of the ethyl acetate fraction of Preparation Example 3

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

0.13 mg of vitamin

0.15 mg of vitamin B ₂

0.5 mg of vitamin B ₆

Vitamin B ₁₂ 0.2 g

10 mg vitamin C

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 mg of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

15 mg of potassium phosphate monobasic

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

100 mg of calcium carbonate

24.8 mg of magnesium chloride

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

&Lt; Formulation Example 3 > Preparation of health functional food (beverage type)

1000 mg of the ethyl acetate fraction of Preparation Example 3

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water was added to a total of 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 for about 1 hour. The resulting solution was filtered and sterilized in a sterilized 2 liter container, And used for manufacturing.

Although the composition ratio is relatively mixed with the ingredient suitable for the favorite drink, it is also possible to arbitrarily modify the blending ratio according to the regional or national preference such as the demand class, demand country, use purpose, and the like.

&Lt; Formulation Example 4 > Preparation of health functional food (chewing gum)

Gum base 20%

Sugar 76.36 ~ 76.76%

The ethyl acetate fraction of Preparation Example 3 was 0.24 to 0.64%

Fruit flavor 1%

Water 2%

Chewing gum was prepared using the above-mentioned composition and content by a conventional method.

&Lt; Formulation Example 5 > Production of health functional food (wheat flour food)

0.5 to 5 parts by weight of the ethyl acetate fraction of Preparation Example 3 was added to 100 parts by weight of wheat flour, and a bread, a cake, a cookie, a cracker and a noodle were prepared using this mixture to prepare a health improving food.

&Lt; Formulation Example 6 > Production of health functional foods (dairy products)

5 to 10 parts by weight of the ethyl acetate fraction of Preparation Example 3 was added to 100 parts by weight of milk, and various dairy products such as butter and ice cream were prepared using the milk.

Claims

A pharmaceutical composition for treating or preventing obesity, diabetic or non-alcoholic fatty liver disease, comprising an extract of Rana cunea as an active ingredient.

The pharmaceutical composition for treating or preventing obesity, diabetes or non-alcoholic fatty liver disease according to claim 1, wherein the extract is selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, an extract of a mixed solvent thereof, and a hot water extract.

The method for treating or preventing obesity, diabetic or non-alcoholic fatty liver disease according to claim 2, wherein the extract is from ethyl acetate, hexane or toluene fraction of water, an alcohol having from 1 to 4 carbon atoms or an extract of a mixed solvent thereof &Lt; / RTI >

A health functional food composition for improving or preventing obesity, diabetes, or nonalcoholic fatty liver diseases, which comprises an extract of Rumex Fruit as an active ingredient.

[Claim 5] The composition according to claim 4, wherein the extract is a water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof.