KR100686362B1 - A composition comprising an extract of zizyphus jujuba mill. var. inermis rehder for treating and preventing obesity - Google Patents

Abstract

A composition for treating and preventing obesity comprising the extract of Zizyphus jujuba Mill. var. inermis Rehder is provided to inhibit body weight increase, reduce neutral lipid concentration and cholesterol concentration, and increase high density cholesterol concentration. The composition for treating and preventing obesity comprises the extract of Zizyphus jujuba Mill. var. inermis Rehder as an effective ingredient, wherein the Zizyphus jujuba Mill. var. inermis Rehder extract is prepared with a solvent selected from water, ethanol and methanol; the amount of the Zizyphus jujuba Mill. var. inermis Rehder extract is 0.1-50 wt.%; the daily dosage of Zizyphus jujuba Mill. var. inermis Rehder extract is 0.0001 to 100 mg/kg; and the composition is a health food composition.

Description

A composition comprising an extract of Zizyphus jujuba Mill. var. inermis Rehder for treating and preventing obesity}

1 is a diagram showing the weight change measurement results by the extract of blue jujube in diet-induced obesity model rats,

Figure 2 is a diagram showing the results of measuring the change in the concentration of triglycerides in blood by the extract of blue jujube in diet-induced obesity model rats.

Figure 3 is a diagram showing the results of measuring the change in blood cholesterol concentration by the extract of blue jujube in diet-induced obesity model rats

Figure 4 is a diagram showing the results of measuring the weight change of the posterior cavity fat by the blue jujube extract in diet-induced obesity model rats.

The present invention relates to a composition for the prevention and treatment of obesity, comprising blue extract.

In recent years, as the eating habits have been westernized and the culture level has been improved, simple obesity has increased significantly. Obesity has been a cause of involvement or exacerbation of various diseases such as hypertension, arteriosclerosis, fatty liver and diabetes. Therefore, it is better to prevent obesity in advance, and in case of obesity, it is very important for the prevention and health of various diseases to control body metabolism smoothly by reducing body fat.

Until now, in China and Japan, Gambia tea, which has a long history of drinking, has been used for reducing obesity, but this is not a product that is very inconvenient and easy to drink. The demand for drinks is increasing.

There are various types of diet products on the market, such as dietary fiber products, products using milk proteins, and granular products using herbal ingredients. In addition, diet drinks have also been developed and marketed, but these drinks are not scientifically analyzed for the analysis of active ingredients and the mechanism of expression of efficacy. In some cases, it is only.

Blue jujube is a mature fruit of Zizyphus jujuba Mill. It is native to southeastern Europe and southeastern Asia, and is cultivated in the vicinity of Korean villages. Trees have thorns and bunches of thorns on nodes. The leaves are alternate, egg-shaped or long egg-shaped, with three leaf veins clearly visible. The upper side of the leaf is light green and slightly polished, and there are fine teeth on the edge of the leaf. A petiole has thorn leaves on petioles. Pale yellow-green flowers bloom in June, forming a short inflorescence in the axilla. Calyxes, petals, and stamens are 5 in number and pistil is 1 in number. Fruits are nucleus, oval, reddish brown, glossy. Surgical blood is thin, sticky and sponge-like. The inner skin is hard and has seeds in it and ripens in September. Jujube, which is a fruit, is eaten raw or used for cooking rice cakes, medicines, etc., and dried jujube in September. The herbal medicine has nourishment, tonic, Jinhae, analgesic, and detoxification. Used for drug addiction. Jujube contains alkaloids, proteins, sugars, organic acids, mucus, vitamins A, B2, C, trace amounts of calcium, phosphorus, iron, etc. (Herbal Medicine, Committee for Compiling Teaching Materials, Younglimsa, P558, 2004).

However, nothing has been taught or described in the literature regarding the use of jujube extract in relation to the obesity treatment and prophylactic effect.

Therefore, the present inventors ingested the blue jujube extract of the present invention in obese model rats induced by a high fat, high cholesterol diet, the weight gain inhibitory effect, lowering the concentration of triglycerides and cholesterol in the body, the concentration of high density cholesterol Has completed the present invention by confirming the effect of increasing fat metabolism and inhibiting fat accumulation.

An object of the present invention is to provide a pharmaceutical composition and health functional food for the prevention and treatment of obesity containing blue jujube extract.

In order to achieve the above object, the present invention provides a composition for the prevention and treatment of obesity containing the blue jujube extract.

The extract includes water, ethanol, lower alcohols such as methanol or mixed solvents thereof, preferably water or ethanol soluble extract, more preferably 10 to 95% of the soluble extract in ethanol.

Hereinafter, the present invention will be described in detail.

Blue jujube extract of the present invention can be obtained as follows.

The blue jujube extract of the present invention is chopped and dried blue jujube, and then a mixed solvent of water and ethanol 1 to 50 times, preferably 10 to 30 times the volume of 10 to 50 ℃, preferably at room temperature as an extraction solvent 1 hour to 5 days, preferably 1 to 4 days extraction method such as cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, preferably by cold extraction, or distilled water with an extraction solvent 1 to 40 Pear, preferably 5 to 20 times the volume amount of 0.5 to 10 hours, preferably 1 to 5 hours at an extraction temperature of 30 to 150 ℃, preferably 60 to 120 ℃, cold extraction, hot water extraction, ultrasonic Extraction method such as extraction, reflux cooling extraction, and the like, preferably after reflux cooling extraction, the extract is centrifuged, filtered and concentrated to obtain the extract of the present invention.

In addition, conventional fractionation processes can also be carried out (Harborne JB Phytochemical methods: A guide to modern techniques of plant analysis, 3rd Ed. , Pp 6-7, 1998).

The blue jujube extract obtained by the above method was ingested in a high-fat, high-cholesterol-induced obesity model rat, resulting in weight loss inhibitory effect, lowering the concentration of triglycerides and cholesterol in the body, and increasing the concentration of high density cholesterol. It was confirmed that the effect of promoting fat metabolism and inhibiting fat accumulation was excellent.

The present invention provides a pharmaceutical composition for the prevention and treatment of obesity containing the blue jujube extract obtained by the production method as an active ingredient.

The pharmaceutical composition for preventing and treating obesity of the present invention comprises 0.1 to 50% by weight of the extract based on the total weight of the composition.

Pharmaceutical compositions comprising the extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

Pharmaceutical compositions comprising extracts according to the invention, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Can be formulated and used. Carriers, excipients and diluents that may be included in the composition comprising the extract or compound include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, Calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. Or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the extract of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 20 to 40 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.

The extract of the present invention can be administered to mammals such as mice, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

The present invention provides a dietary supplement comprising the above-mentioned blue jujube extract and a foodstuff acceptable food supplement additive exhibiting the effect of preventing and treating obesity. Examples of the food to which the extract can be added include various foods, beverages, gums, teas, vitamin complexes, health functional foods, powders, granules, tablets, capsules or beverages.

It may also be added to food or beverages for the purpose of preventing and treating obesity. At this time, the amount of the extract in the food or beverage can be added in 0.01 to 15% by weight of the total food weight, the health beverage composition is added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 ml Can be.

The health functional beverage composition of the present invention is not particularly limited to other ingredients except the above-mentioned blue jujube extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. have. 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 conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.

In addition to the above, the blue jujube extract of the present invention is a variety of nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, such as flavoring agents, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid And salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the extract of the present invention may contain natural fruit juice and fruit flesh for the production of fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is usually selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

Hereinafter, the present invention will be described in detail by the following Examples and Experimental Examples.

However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.

Example 1 Preparation of Blue Jujube Extract

1-1. Preparation of Blue Jujube Water Extract

500 g of blue jujube harvested directly on the farm was washed with clean water, and then 6L of secondary distilled water was added, extracted with an electric bath for 3 hours, filtered, concentrated in a vacuum rotary concentrator, and freeze-dried in a freeze dryer. 25 g of jujube water extract was obtained (yield 5%).

1-2. Preparation of Blue Jujube Ethanol Extract

500g of directly harvested blue jujube was washed with clean water, dried naturally and powdered. After adding 10% of 70% ethanol and extracting it twice at room temperature for about 72 hours, it was filtered and dried under reduced pressure. 20 g of extract were obtained (yield 4%).

Reference Example 1. Experimental Animal

Animals were purchased from male mice (C57BL / 6J, 5 weeks old) (Hyochang Science), and were fed high fat and high cholesterol diets containing 30% fat and 1% cholesterol for 17 weeks (High-fat & high). -cholesterol diet therapy induced obesity. High breeding environment was maintained at a constant temperature of 25 ± 2 ℃, constant humidity 50 ± 5%, 12-hour dark-light cycle (dark-light cycle).

Experimental Example 1. Measurement of weight gain

The following experiment was performed to determine the effect of the blue jujube extract of the present invention on the weight change of the animal model.

The obese rats induced by the method of Reference Example 1 were added orally with 0.5% of blue jujube extract to the feed for 4 weeks and orally administered daily. In order to confirm the weight change of obese rats, body weights were measured each week after the administration of the blue jujube extract. In order to measure the weight of the rat, a box containing the rat was placed on the scale and the zero point was adjusted, and then the value when the rat's behavior stopped.

As a result of the experiment, as shown in Figure 1, it was confirmed that when the addition of 0.5% of blue jujube extract to the feed for 4 weeks, compared to the control group did not administer 15% excellent weight gain inhibitory effect up to 4 weeks .

Experimental Example 2 Measurement of Changes in Lipids in Blood

In order to determine whether there is an effect of reducing blood fat and cholesterol concentration in animal models using the extract of blue jujube of the present invention, the experiment was performed by the following procedure by applying the experimental method described in the existing literature (Van Heek et al., J. Clin. Invest. , 99 , 385-390, 1997).

The obese rats induced by the method of Reference Example 1 were added orally to the feed by 0.5% for 4 weeks, and divided into the experimental group and the control group by daily oral administration. Mice five weeks after oral administration of the blue jujube extract were fasted for 12 hours before sacrifice, and then fasted. Then, anesthesia was injected by intraperitoneal injection of 50 mg / kg sodium pentobarbital, and fasting blood was collected from the inferior venacava. The collected blood was centrifuged for 4-15 minutes at 3,000 rpm after treatment with anticoagulant to separate plasma.

 1.5 ml of neutral lipid measurement kit solution and 1.5 ml of cholesterol measurement kit solution were mixed 1: 1 in plasma and reacted at 37 ° C. for 5 minutes, and total cholesterol was 492 nm and neutral in a microplate reader. Fats were quantified in blood concentration [mg / dl] by measuring absorbance at 540 nm, respectively. Quantitative conversion of triglycerides and cholesterol was determined by using a standard concentration curve with the values obtained by measuring absorbance for each standard solution by concentration.

Experimental results As shown in Figures 2 and 3, it was confirmed that the concentration of triglycerides and cholesterol in the blood of the rats ingested the extract of blue jujube in the experimental group and the HDL in the blood was increased. This means that HDL, which plays a role in moving cholesterol to the liver, increases in blood and metabolizes cholesterol actively, and it was confirmed that blue jujube extract smoothed the metabolism of cholesterol in obese mice.

Experimental Example 3. Measurement of fat accumulation effect in the body

In order to determine the effect of the blue jujube extract of the present invention on the accumulation of fat in the body, the following experiment was performed.

Rats 5 weeks after oral administration of the blue jujube extract were fasted for 12 hours before sacrifice, and fasted, and anesthetized by intraperitoneal injection of 50 mg / kg sodium pentobarbital. After dissection, the fat was extracted from the abdominal cavity and weighed.

Experimental results As shown in Figure 4, it was confirmed that the experimental group administered with the blue jujube extract for 4 weeks in obese rats showed a 9% fat accumulation inhibitory effect compared to the control group.

Experimental Example 4. Acute Toxicity Test

Changes were observed by oral administration of 2 g / kg of the blue jujube extract of Example 1 to 10 mice, but no death was observed, and no significant abnormalities were found in weight gain and feed intake. Therefore, the extract of blue jujube of the present invention was confirmed to be a safe drug.

Examples of the formulation of the composition are given below, but the present invention is not intended to be limited thereto but merely to explain in detail.

Hereinafter, a preparation example of a composition containing an extract of the present invention will be described, but the present invention is not intended to be limited thereto but only to be described in detail.

Formulation Example 1 Preparation of Powder

Blue Date Extract 20 mg

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation Example 2 Preparation of Tablet

Blue Date Extract 10 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation Example 3 Preparation of Capsule

Blue Date Extract 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation Example 4 Preparation of Injection

Blue Date Extract 10 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO _4, 12H ₂ O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation Example 5 Preparation of Liquid

Blue Date Extract 20 mg

10 g of isomerized sugar

5 g of mannitol

Purified water

After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding lemon flavor appropriately, mixing the above components, adding purified water, adjusting the whole to 100 ml by adding purified water, and then filling into a brown bottle. The solution is prepared by sterilization.

Formulation Example 6 Preparation of Healthy Food

Blue Date Extract 1000 mg

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinic Acid 1.7 mg

Folate 50 ㎍

Calcium Pantothenate 0.5mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.

Formulation Example 7 Preparation of Healthy Drink

Blue Date Extract 1000 mg

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 ml of purified water

After mixing the above components according to a conventional healthy beverage production method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2L container, sealed sterilization and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.

Although the composition ratio is mixed with a relatively suitable component for a preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

 Cheongjuju extract of the present invention is a high fat, high cholesterol diet-induced fat metabolism-promoting effect and fat accumulation in obese model rats to lower the weight gain inhibitory effect, decrease the concentration of triglyceride and cholesterol in the body, increase the concentration of high density cholesterol Inhibitory effect fmf can be useful as a pharmaceutical composition and health functional food for the prevention and treatment of obesity.

Claims (4)

A pharmaceutical composition for the prevention and treatment of obesity, containing blue jujube extract as a main ingredient. The pharmaceutical composition according to claim 1, wherein the extract is an extract available in a solvent selected from water, ethanol, methanol or a mixed solvent thereof. Health functional food for obesity prevention and improvement containing blue jujube extract as an active ingredient. delete

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