KR20130098028A - A composition comprising the extract of diospyros kaki as an active ingredient showing anti-obesity and anti-hyperlipidemia activity - Google Patents

Abstract

PURPOSE: A composition for preventing and treating hyperlipidemia or obesity is provided to significantly reduce body weight of an experimental animal which takes in high fat feed, the weight of fat around epididymis, and lipid content in blood using a Diospyros kaki extract, thereby producing a pharmaceutical composition or a health food for preventing and treating hyperlipidemia or obesity. CONSTITUTION: A pharmaceutical composition for preventing and treating hyperlipidemia or obesity contains a Diospyros kaki extract as an active ingredient. The extract is prepared using a solvent among water, C1-C4 alcohol, or a mixture thereof. The extract is solubilized in water or a mixture solvent of water and ethanol. The extract is a fermented extract which is prepared by crushing immature Diospyros kaki, dipping the crushed Diospyros kaki in the solvent at 0-70°C for 2-30 days, and filtering.

Description

A composition comprising the extract of Diospyros Kaki as an active ingredient showing anti-obesity and anti-hyperlipidemia activity}

It relates to a composition for the treatment and prevention of hyperlipidemia or obesity containing the Sicily extract of the present invention as an active ingredient.

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12. Public information, Dohae Yakdae Dictionary, Yeonglimsa, p915-918, 1998

The present invention relates to a composition for the treatment and prophylaxis of hyperlipidemia or obesity containing a syrup extract as an active ingredient.

In addition to economic development, our lifestyle has developed into Western developed countries, and as dietary changes and physical activities decrease, obesity increases due to increased body fat and metabolic imbalances, resulting in diabetes, hyperlipidemia, and blood clots. The incidence of metabolic syndrome, which is a complex of cardiovascular diseases such as disorders, continues to increase. Obesity is not a disease caused by one cause but is a complex syndrome caused by genetic, environmental, and social factors. It is caused by accumulation of triglycerides in fat tissue, which is not consumed by metabolic activity after excessive intake of energy. [3]. In addition, increased fatty acid levels and abdominal obesity seen in obesity are common symptoms of hyperlipidemia and type 2 diabetes. Increased free fatty acids cause ventricular hypertrophy [4], and abdominal fat accumulation causes insulin resistance. A close association was reported with [5]. As a result, it causes a lifestyle disease such as hypertension, arteriosclerosis, diabetes, and hyperlipidemia, or it is a factor deteriorating health.

Although it is important to prevent health problems caused by obesity, patients need long-term and effective obesity management and treatment. Current methods for treating obesity include lifestyle corrections such as diet therapy, exercise therapy and behavioral therapy, and drug and surgical treatments [6]. In general, lifestyle correction alone has limited limitations on obesity treatment. In many cases, medication is required along with lifestyle correction. The use of drugs for the treatment of obesity has been tried for a long time, but the obesity drugs currently approved by the US FDA for long-term use due to a number of serious side effects are sibutramine, pancreatic and digestive system that inhibit the reabsorption of norepinephrine and serotonin. There is an orlistat that works by inhibiting lipase secreted from [7.8]. However, none of these drugs are widely used due to some limitations due to side effects [9,10]. In order to solve this problem, the development and research of obesity treatments continue, but the synthetic anti-obesity drugs have not yet developed a complete treatment with no side effects. Therefore, researches are being actively conducted to develop functional materials that are effective for the most control and have fewer side effects in natural products and develop them into medicines or health functional foods according to their anti-obesity mechanism [11].

Sicily used in this study was a glutinous fruit obtained by processing the immature fruit of Diospyros Kaki grown in sub-Gyeonggi province of Ebenaceae. Pour and stir several times, mix well, and leave it for 20 days, then squeeze the residue to leave the colorless gelatinous liquid, known ingredients such as shibutol (tan), choline (choline), acetyl choline (acetyl choline), etc. It is known to contain. (Interpretation of Information, Dohae Yakdae Dictionary, Yeonglimsa, p915-918, 1998).

However, none of the above documents discloses or teaches the therapeutic effect of hyperlipidemia or obesity, which contains a syrup extract as an active ingredient.

Accordingly, the present inventors conducted the present invention to find a natural product with excellent efficacy in obesity, the body weight of the experimental animal ingested high-fat feed through the in vivo experiments, the weight of the epididymal fat, blood Since the lipid content was significantly reduced, the composition was confirmed to be useful as a pharmaceutical composition or health functional food for preventing and treating hyperlipidemia or obesity, thereby completing the present invention.

In order to solve the above object, the present invention provides a pharmaceutical composition for the treatment and prevention of hyperlipidemia or obesity containing a syrup extract as an active ingredient.

In another aspect, the present invention provides a health functional food for the prevention and improvement of hyperlipidemia or obesity containing the syrup extract as an active ingredient.

Sicilian extracts as defined herein are water, C ₁ to C ₄ lower alcohols after mashed immature persimmon (Diospyros Kaki), preferably a young persimmon (showing blue in appearance) harvested 3 to 6 months after cultivation, or As these mixed solvents, preferably water or extracts soluble in water and ethanol mixed solvents, more preferably about 2 to 30 days at a temperature of about 10 to 80 ° C., preferably 20 to 50 ° C. in water, Preferably fermented blueish astringent persimmon fermentation extract prepared by immersion for about 3 to 20 days and then filtered.

Hereinafter will be described in more detail the method for obtaining a syrup extract of the present invention.

For example, the method of obtaining the syrup extract of the present invention comprises the first step; After mashed immature persimmon (Diospyros Kaki), preferably persimmon appearance blue, harvested 3 to 6 months after cultivation, about 1 to 100 times the sample weight, preferably about 1 to 50 times Pear (w / v) volume of water, C ₁ to C ₄ lower alcohols, or a mixed solvent thereof, preferably water or water and ethanol as the extraction solvent, about 3 to 70 ° C, preferably 10 to Performing a fermentation process soaking for about 2 to 30 days, preferably about 5 to 20 days, at a temperature of 30 ° C .; A third step of filtering and extracting the extract obtained in the above step under reduced pressure; It is possible to obtain a sile extract of the present invention through a step comprising the method of the fourth step of freeze drying the concentrated extract.

In another aspect, the present invention provides a pharmaceutical composition and health functional food for the treatment and prevention of hyperlipidemia or obesity containing the manufacturing method and the Sicilian extract prepared by the manufacturing method as an active ingredient.

Since the prepared Sicil extract significantly reduced the body weight, the weight of the epididymis fat, and the blood lipid content of the experimental animals ingested high fat feed in vivo, the composition prevented hyperlipidemia or obesity. And it was confirmed that it is useful as a therapeutic pharmaceutical composition or dietary supplement.

The composition of the present invention comprises 0.01 to 99% by weight of the silycitic extract relative to the total weight of the composition.

However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.

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

The composition containing the extract according to the present invention may be formulated in the form of powders, granules, tablets, capsules, oral preparations such as suspensions, emulsions, syrups and aerosols, external preparations, suppositories and sterilized injection solutions, Examples of carriers, excipients and diluents that can be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, 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 contain at least one excipient, such as starch, calcium carbonate, sucrose, Or lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate 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 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 is preferably administered at a dose of 0.01 mg / kg to 10 g / kg per day, preferably 1 mg / kg to 1 g / kg per day. The administration may be carried out once a day or divided into several doses. Therefore, the dose is not intended to limit the scope of the present invention in any aspect.

The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration can be expected, for example by oral and rectal or intravenous methods.

In another aspect, the present invention provides a health functional food for the improvement and prevention of hyperlipidemia and obesity containing the extract as an active ingredient.

The health functional food containing the extract of the present invention can be used variously for medicines, foods and beverages for prevention and improvement of obesity. Examples of the foods to which the extract of the present invention can be added include various foods, beverages, gums, tea, vitamin complex, leach tea, health supplement foods and the like, and they are in the form of powder, granule, tablet, capsule or beverage Can be used.

Therefore, the present invention also provides a food or food additive containing a syrup extract having an effect of preventing and improving hyperlipidemia and obesity as an active ingredient.

The food forms to which the extract of the present invention can be added include various foods of candy, beverages, gums, tea, vitamin complexes, or foods that are health supplement foods.

The extract of the present invention can be added to food or beverage for the purpose of prevention and improvement of obesity. At this time, the amount of the extract in the food or beverage is generally added to the health food composition of the present invention to 0.01 to 15% by weight of the total food weight, the health beverage composition is 0.02 to 10 g based on 100 ml, preferably Can be added at a ratio of 0.3 to 1 g.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient, such as ordinary beverages, in addition to containing a mixture of the above extract as an essential ingredient in the indicated ratios, have. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and 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 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

Sicily extract of the present invention significantly reduced the body weight, the weight of the surrounding epididymis, the blood lipid content of experimental animals ingested high fat feed through in vivo experiments, the composition prevents hyperlipidemia or obesity and Provides a therapeutic pharmaceutical composition or dietary supplement.

Hereinafter, the present invention will be described in detail with reference to the following Reference Examples and Experimental Examples.

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

Example  One. Sicily  Preparation of extract

The samples used in this experiment were crushed by young Diospyros Kaki (appearing blue in appearance) harvested from 3 months to 6 months (May to August of the year) after cultivation from the Qingdao producing farms. , 10 times (w / v) volume of the sample weight of the water as an extraction solvent, the fermentation process soaked for 10 days at a temperature of about 20 ℃, the extract obtained in the step is filtered and concentrated under reduced pressure A syrup water extract of the invention (hereinafter referred to as DKW) was prepared. Diluted in physiological saline to an appropriate concentration was used for animal experiments.

Experimental Example  One. Sicily  Confirm the effect of extract on obesity

In order to determine the effect on the obesity of the carcass extract obtained in Example 1, using a mouse experimental model induction of obesity in a high fat diet (inhibition efficacy of obesity and hyperlipidemia-induced rats of Taeum-jowitangagambang ethanol extract Park, Chul-hwan , Graduate School of East-West Medical Science, Kyung Hee University, [2007]; Lipid lowering and obesity inhibitory effects of water extracts.Jung-Hoon Shin, Graduate School of Daegu Haany University, [2008])

1. Experimental Animals and Diet

The experimental animals were purchased from Samtako (Osan, Gyeonggi-do) for 6 weeks of age and were adapted to general solid feed for 1 week in the animal breeding facility environment of Wonkwang University. Three were separated and reared. AIN-76A (Research Diets, Inc., D12451, Calorie Composition: 45% Fat, 35% Carbohydrate, 20% Protein) purchased from Central Experimental Animals (Seoul) in order to induce obesity It was used for induction experiments. Experimental group (1) Normal control (N-Con), (2) High fat diet control group (HF-Con), (3) High fat diet +200 mg / kg TA water extract administration group (HF + TAWE 100), (4) high-fat diet + 200 mg / kg TA ethanol extract administration group (HF + TAEE 200) and divided into free diet and water.

TA extracts were suspended in physiological saline so that 200 mg / kg of body weight per day was administered orally for 6 weeks at a certain time every day, and the normal diet and the high-fat diet group were orally administered only physiological saline by the same method. The animal cage was maintained at a temperature of 20 ± 2 ^o C and a relative humidity of 50 ± 10%, and adjusted to a light and dark cycle of 12 hours. All animal experiments were carried out by the Chonbuk National University Institutional Animal Care and Use Committee. It was performed in compliance with animal test ethics rules with approval.

2. weight and Dietary intake  Measure

Dietary intake was measured three times a week and body weight once a week. The weight gain rate of each experimental group was measured at regular intervals at one week intervals during the experimental period. The weight gain was calculated by subtracting the weight before the start of the experiment from the final weight and dividing it by the weight before the start of the experiment. It was divided and calculated.

As a result of testing the effects of carcass extracts on body weight and dietary intake, the extracts were investigated to investigate the effect of carcass water extract (DKW) on weight, dietary intake and energy intake in obese mouse model induced by high-fat diet. Mice were orally administered 200 mg / kg once a day for 5 weeks to measure the change. When the body water extract of the present invention is administered, it was confirmed that both significantly inhibit the weight gain caused by the high fat diet.

3. Serum and Tissue Sampling

The experimental animals were anesthetized with ether at the end of the test, and blood was collected from the heart using a syringe, and serum was separated by centrifugation at 1,900 × g for 20 minutes. Serum lipid content and enzyme activity were used as samples for measurement. The liver and adipose tissue were extracted, rinsed the remaining blood with 0.9% physiological saline, and the water was removed after filtration. The blood and tissue samples were rapidly frozen and stored at -70 ^o C deep freezer until use.

4. Measurement of lipid content in blood

Triglycerides, total cholesterol, and HDL cholesterol content in blood were analyzed according to the provided protocol using enzyme analysis kits (AM203) purchased from Asan (Seoul, Korea). Fat was measured at 550 nm, total cholesterol at 550 nm, and HDL cholesterol at 500 nm. Blood LDL cholesterol content was calculated by Friedewald's equation (22 ).

As a result of testing the effect of wheatgrass extract on blood lipids , blood lipids are a component of various adipose tissues and are involved in the storage of bioenergy, and in obesity, neutral lipid and total cholesterol content are increased. On the other hand, HDL-cholesterol, which acts to remove cholesterol from the blood by transporting cholesterol from peripheral tissues to the liver, reduces the concentration and becomes a danger signal of atherosclerosis. Therefore, in order to investigate the effects of TAWE and TAEE administration on the blood content of neutral lipid, total cholesterol, HDL-cholesterol, LDL-cholesterol, the serum of each experimental group was separated and analyzed.

Sikil water extract (DKW) significantly decreased the blood triglyceride content due to the high fat diet and significantly decreased the total cholesterol content in the blood.

5. Liver tissue  And microscopic observation of adipose tissue

Fatty tissues of liver tissue, epididymal region adipose tissue and kidney region adipose tissue were extracted from the mice, weighed, fixed in 10% formalin solution for 12 hours, and washed with PBS. After preparing the paraffin block was cut into 5μm thickness using a slicer to prepare a tissue section. Tissue sections were deparaffinized with xylene to remove paraffin and stained nuclei and cytoplasm for 5 min with hematoxylin / eosin (Sigma) solution. Tissue morphology of each experimental group was observed under a light microscope (200x).

DKW significantly reduced the total lipid and triglyceride levels of liver tissue and epididymal adipose tissue in mice fed high fat diet.

6. Statistical Processing

The results obtained in the experiments were expressed as mean ± standard error per experimental group and statistically analyzed using Statistical Package for Social Science (SPSS). The statistical significance of the mean difference between groups was analyzed by one-way ANOVA and then verified by Duncan's multiple range test at p <0.05.

Hereinafter, formulation examples of the composition containing the extract of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.

Formulation example  One. Sanje  Produce

DKW 200 mg

Lactose 100 mg

Talc 10 mg

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

Formulation example  2. Preparation of tablets

DKW 200 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

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

Formulation example  3. Preparation of capsules

DKW 200 mg

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed in accordance with a conventional method for producing a capsule, and filled in a gelatin capsule to prepare a capsule.

Formulation example  4. Preparation of injections

DKW 200 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO _{4 ,} 12H ₂ O 26 mg

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

Formulation example  5. Liquid  Produce

DKW 200 mg

10 g per isomer

5 g mannitol

Purified water

Each component was added and dissolved in purified water according to the usual liquid preparation method, 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 added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

Formulation example  6. Manufacture of health food

DKW 1000 mg

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

0.13 mg vitamin B1

0.15 mg of vitamin B2

0.5 mg vitamin B6

0.2 [mu] g vitamin B12

10 mg vitamin C

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ 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.

Formulation example  7. Manufacture of health drinks

DKW 1000 mg

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 heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, &Lt; / RTI &gt;

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

Claims (7)

A pharmaceutical composition for the treatment and prevention of hyperlipidemia or obesity, containing a syrup extract as an active ingredient. The pharmaceutical composition of claim 1, wherein the extract is water, C ₁ to C ₄ lower alcohols, or a mixed solvent thereof. The pharmaceutical composition according to claim 2, wherein the extract is an extract available in water or a mixed solvent of water and ethanol. The method of claim 1, wherein the siil extract is immersed in water, C ₁ to C ₄ lower alcohol or a mixed solvent thereof for 2 to 30 days after crushing the diospyros Kaki A pharmaceutical composition, characterized in that the fermented extract prepared by the step of filtering after. Health functional food for the prevention and improvement of hyperlipidemia or obesity, containing the extract of Sicily as an active ingredient. The health functional food according to claim 5, wherein the health functional food form is in the form of a beverage, a gum, a tea, a vitamin complex, an oil-immersion tea, a health supplement, a powder, a granule, a tablet, a capsule or a drink. Food or food additive containing wheatgrass extract having an effect of preventing and improving obesity as an active ingredient.