JP2015502954A - A composition for preventing or treating dyslipidemia, comprising an aqueous extract of Aguitake as an active ingredient - Google Patents

Abstract

  The present invention relates to a composition for the prevention or treatment of dyslipidemia containing a water extract of Agaricus as an active ingredient and a health functional food containing the composition, and the water extract of Agaricus has a cholesterol esterase activity and a medium. There is an effect that the ability to inhibit the absorption of fatty fat is excellent compared to ethanol extract.

Description

  The present invention relates to a pharmaceutical composition and a health supplement composition containing a water extract of Agaricus that can be used for the purpose of preventing or treating dyslipidemia.

  Dyslipidemia refers to a state where the fat component is high in the blood. Generally, when total cholesterol exceeds 240 mg / dl or neutral fat is 200 mg / dl or more, it is called dyslipidemia. Dyslipidemia is known as the main cause of cholesterol blockage blocking blood vessels and inhibiting blood circulation, leading to hypertension, myocardial infarction and stroke. The number of dyslipidemic patients in Korea is also steadily increasing, and the number of dyslipidemic patients is increasing rapidly worldwide, and more dyslipidemic patients are expected to increase. Therefore, many reports on the treatment and prevention methods and treatment methods for dyslipidemia have been presented.

  The cause of dyslipidemia is metabolic disorders due to genetic factors, but it is also caused by accumulation of cholesterol in the blood from other causes such as high calorie diet and obesity triggered by lack of exercise (Bray) GA, Popkin BM .: Dietary fat intact dose effect obesity.Am. J Clin.Nutr 68: 1157-1173 (1998)). In particular, increased intake of high-fat diets due to Westernized diets is considered to be the main reason for dyslipidemia. Currently, development of candidate efficacy substances such as cholesterol absorption inhibitors for the prevention or treatment of dyslipidemia is being actively carried out around the world. It is growing.

  Currently, statins are widely used as therapeutic drugs for dyslipidemia. This series of drugs is an HMG-CoA reductase inhibitor and has the effect of suppressing cholesterol synthesis and lowering blood LDL-cholesterol. In addition, ezetimibe, niacin, and fibrate preparations are mainly used, but rarely during the administration of drugs, muscle pain, constipation, digestive disorders and liver dysfunction Side effects such as occurrence may occur.

  On the other hand, about 10,000 kinds of mushrooms have been reported all over the world, and many researches have been conducted in developed countries such as Europe, the United States and Japan in order to secure edible and medicinal value as useful microorganism resources. Has been done. In particular, bioactive substances produced by mushrooms are safe in terms of toxicity with few side effects, and many research results show that they have various functions such as regulation of immune system functions, anticancer effects, and regulation of metabolism in the human body. Has been reported.

  The inventors of the present invention started the present invention by conducting research on natural substances that have almost no side effects in the body and inhibit the absorption of cholesterol in the body and have an effect of improving dyslipidemia.

  The Aguitake (Pleurotus eryngii var. Ferulea (Pf.)) Is a variant of Elingi, the English name is Ferula Oyster Mushroom (Ferula Oyster Mushroom), and in other words, it is the oyster mushroom of the Agi tree. It grows wild in the Xinjiang region of Xinjiang, a dry region of China, and is suitable for cultivation in the spring and autumn of Korea at an intermediate temperature of 8-20 ° C.

  Agittake, which grows naturally in China and Central Asia, is known as a medicinal plant that relieves clogged areas, eliminates coughing and inflammation, and is effective against gastrointestinal diseases. It is a highly functional mushroom that has been introduced to relieve inflammation and is effective for obstetrics and gynecological diseases.

  The inventors of the present invention have researched on inhibitors that suppress cholesterol and neutral fat reabsorption or reduce blood cholesterol in the small intestine, a natural substance that can replace drugs such as statins. As a result, it was confirmed that the extract of Agittake, especially the water extract of Agittake, effectively inhibited the absorption of blood cholesterol and neutral fat, and the present invention was completed.

  Therefore, the present invention provides a composition containing water for inhibiting absorption of cholesterol and neutral fat in the body, and a medical composition for prevention or treatment containing the same as an active ingredient, with few side effects in the body appearing. And providing health functional foods.

  The above-mentioned object of the present invention was achieved by obtaining an aqueous extract of Agaricus and using this as a test material to verify and evaluate the improvement effect of dyslipidemia.

  The composition comprising the water extract of the present invention as an active ingredient has an excellent effect that can be usefully used for the prevention or treatment of dyslipidemia by inhibiting absorption of cholesterol and neutral fat in the body. is there.

It is the graph which showed by comparison the CEL activity inhibitory effect of the extract of Agaricus of the Example and comparative example of this invention. 3 is a graph showing a comparison of CEL activity according to the concentration of a water extract of Aguitake according to an embodiment of the present invention. 5 is a graph showing a comparison of TGL activity according to the concentration of a water extract of Aguitake according to an embodiment of the present invention. 3 is a graph showing a comparison of cholesterol absorption from the gastrointestinal tract of blood of Aguitake according to an embodiment of the present invention and orlistat, a conventional fat inhibitor.

  The water extract of Aguitake may be produced by a normal method for producing a plant extract. Most preferably, the agaric is dried at a temperature of 15 ° C. and then pulverized, then the residue is removed, and 0.1 to 20 g of the pulverized product is added per 100 mL of water, most preferably 1 to 5 g of pulverized product is added per 100 mL of extraction solvent And extract. Drying with hot air at 40 ° C. or higher was not preferable. In addition, when the content of the agaric pulverized product is too small with respect to the extraction solvent, the cholesterol absorption effect of Aitake is not sufficiently exhibited, and when the content is excessive with respect to the amount of the extraction solvent, the effect accompanying the increase in content is increased. However, it is not preferable from the viewpoint of productivity because the production cost increases.

  As for the extraction conditions of Agittake, preferably Agittake is mixed with water as an extraction solvent and then extracted at a temperature of 20 to 60 ° C. for 12 to 36 hours, most preferably at a temperature of 30 to 40 ° C. for 20 to 24 hours. There must be.

  When extracting under a low temperature condition of 20 ° C. or lower, a long time is required to extract the effective extraction component, and when extracting under a high temperature condition of 60 ° C. or higher, the activity is unfavorable. In particular, a water extract extracted with hot water at 100 ° C. for 15 minutes or more could not be used because of its lack of activity.

  When the extraction time is shortened to 12 hours or less, the concentration of the extracted active ingredient is low, and when extracting for a long time of 36 hours or longer, the concentration of the extracted active ingredient increases slightly as the extraction time increases. This is not preferable from the viewpoint of productivity.

  Furthermore, the water extract of Aguitake extracted by the above method is filtered through a filter cloth, etc., and the filtrate is centrifuged to remove the precipitate, and then concentrated under reduced pressure or concentrated, and then freeze-dried. It was preferable to use it.

  On the other hand, the content of the water extract of Aguitake which is an active ingredient in the composition for treating or preventing dyslipidemia of the above-mentioned embodiment is preferably 0.01 to 30% by weight. When the content of the water extract of Aguitake, which is an active ingredient, is less than 0.01% by weight, the effect of inhibiting the absorption of cholesterol in the body is negligible, and when it exceeds 30% by weight, the inhibitory activity associated with the increase in the content is reduced. The increase effect is negligible and not economical. Preferably the content of the water extract of Agaricus in the composition was 0.001 to 50% by weight, most preferably 0.1 to 30% by weight.

  The present invention provides a pharmaceutical product for preventing or treating dyslipidemia comprising an aqueous extract of Agaricus contained in the composition as an active ingredient according to an embodiment. Such a pharmaceutical product containing the water extract of Agaricus as an active ingredient can further contain appropriate carriers, excipients and diluents usually used in the production thereof.

  Carriers, excipients, and diluents that can be included in a pharmaceutical product containing the water extract of Agittake of the present invention as an active ingredient include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum And alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

  The pharmaceuticals containing the water extract of the present invention as an active ingredient can be used as oral dosage forms such as powders, granules, tablets, suspensions, emulsions, and syrups, respectively, by a conventional method.

  The oral dosage form is meant to include solid preparations and liquid preparations for oral administration, and solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like. Such a solid preparation can be prepared by mixing the extract with at least one excipient such as starch, calcium carbonate, sucrose, or lactose, gelatin, and the like. can do.

  In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. As liquid preparations for oral use, suspensions, liquids for internal use, oils, syrups, etc. are applicable, but various excipients other than water, liquid paraffin, which are commonly used simple diluents, For example, wetting agents, sweeteners, fragrances, preservatives and the like can be included.

  The preferred dosage of the pharmaceutical composition containing the water extract of the present invention is different depending on the condition and body weight, the degree of disease, the drug form, the administration route and the period, but can be appropriately selected by those skilled in the art. Preferably, the pharmaceutical product containing the water extract of Agittake of the present invention as an active ingredient is more effective at an adult standard (60 kg body weight) 0.0001 to 100 mg / kg per day based on the amount of the water extract of Aguitake. Specifically, it is preferably administered at 0.01 to 10 mg / kg. The number of administrations can be administered once a day, or can be divided into several times. The dose and the number of doses do not limit the scope of the present invention in any way.

  According to another embodiment of the present invention, there is provided a functional health food for improving dyslipidemia comprising an aqueous extract of Agaritake as an active ingredient. As used herein, “healthy functional food” means a natural product or processed product containing one or more nutrients, and preferably means a state that can be eaten directly after a certain degree of processing. To do.

  Examples of the health functional food to which the water extract of the agaric of the present invention can be added include various foods, beverages, gums, teas, and vitamin complex agents. Furthermore, the foods according to the present invention include special nutritional foods (eg, prepared milk, infant food, etc.), processed meat products, fish products, tofu, mucous, noodles (eg, ramen, udon), health supplements. , Seasoned foods (eg, soy sauce, miso, gochujang, mixed soy), sauces, confectionery (eg, snacks), dairy products (eg, fermented milk, cheese), other processed foods, kimchi, pickles ( Various kimchi, pickles, etc.), beverages (eg, fruits, vegetable beverages, soy milk, fermented beverages, etc.), natural seasonings (eg, ramen soup, etc.), but are not limited thereto. The food, beverage or food additive can be produced by a normal production method.

  In this specification, functional food means a group of foods that have been given added value so that the function of the food is acted on and expressed for a specific purpose using physical, biochemical, or biotechnological techniques. Or food that has been designed and processed so that the body's body regulation functions relating to biological defense rhythm adjustment, disease prevention and recovery, etc. possessed by the composition of the food are fully expressed in the living body. The functional food may include food supplements that are pharmaceutically acceptable, and may further include appropriate carriers, excipients, and diluents commonly used in the production of functional foods. .

  In this specification, a drink means the generic name of the drink for eliminating thirst and enjoying a taste, and intends to include a functional drink. There are no particular restrictions on the other ingredients except that the beverage contains the water extract of Agittake as an essential ingredient in an instructed proportion, and there are various flavoring agents or natural ingredients like ordinary beverages. Carbohydrates can be included as additional ingredients. Examples of the natural carbohydrate include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as normal sugars such as dextrin and cyclodextrin, and xylitol, sorbitol and erythritol. Such as sugar alcohol. Natural flavors (thaumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavoring agents other than those described above. May generally be about 1-20 g, preferably 5-12 g, per 100 mL of the composition of the present invention, otherwise the composition of the present invention produces natural fruit juices, fruit juice drinks, vegetable drinks. It can further contain pulp to make it.

  In addition to the above, the health functional food of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers (cheese, chocolate, etc.), pectic acid And salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, water, carbonates used in carbonated beverages, and the like. . Such components can be used alone or in combination. The ratio of such additives is not so important, but can be selected in the range of 0 to 20 parts by weight per 100 parts by weight of the water extract of the present invention.

  In this specification, the functional beverage is a group of beverages that are given added value so that the function of the beverage is acted and expressed for a specific purpose using physical, biochemical, biotechnological techniques, etc. Or a beverage designed and processed so that the body regulation functions relating to biological defense rhythm adjustment, disease prevention and recovery, etc. possessed by the composition of the beverage are sufficiently expressed to the living body.

  The functional beverage is not particularly limited as long as it contains the water extract of Agittake of the present invention as an essential component at the indicated ratio, and various flavoring agents or natural ingredients such as ordinary beverages are not limited. Carbohydrates and the like can be included as additional components. Examples of the natural carbohydrate include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as normal sugars such as dextrin and cyclodextrin, and xylitol, sorbitol and erythritol. Such as sugar alcohol. Natural flavors (thaumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavoring agents other than those described above. Is generally about 1-20 g, preferably 5-12 g, per 100 mL of the composition of the present invention.

  In addition, in the health functional food for the purpose of improving or preventing dyslipidemia, the amount of the extract may be included at 0.01 to 15% by weight of the total food weight, and the beverage composition is based on 100 mL. It can be contained at a ratio of 0.02 to 5 g, preferably 0.3 to 1 g.

  Meanwhile, the present invention provides a method for manufacturing the water extract of Aguitake as described above according to another embodiment.

  According to an embodiment of the present invention, there is provided a method for preparing an aqueous extract of agaric mushroom comprising: preparing agaric powder; mixing the agaric powder with water; and mixing the mixture at a temperature of 20-60 ° C. Time, including the stage of extraction.

  Hereinafter, the configuration and effects of the present invention will be described in more detail through specific embodiments of the present invention. However, the following examples are only for understanding the invention more clearly, and the scope of the invention is not limited to the following examples.

  However, it can be said that, for example, agaric powder, which is outside the scope of the present invention, does not belong to the scope of the present invention because it has no inhibitory effect on cholesterol esterase activity as a result of repeated experiments by the present inventors.

[Example] Preparation of water extract of agaric mushroom A dried mushroom (Pleurotus eringii var. Ferulea (Pf.)) Was purchased in the market, coarsely pulverized, placed in a bag made of gauze, and extracted solvent per gram of powder. After mixing with 50 mL of water, the mixture was extracted into a shaking incubator for 24 hours at 37 ° C. The supernatant of the shaking incubator was centrifuged at 2500 rpm for 10 minutes, and the filtered supernatant was collected and used as a test material. did.

[Comparative Example] Preparation of water extract of Agaricus The above-mentioned implementation was performed except that ethanol (99.9% (v / v)) 70% and 100% 100 mL each were used instead of 50 mL water as an extraction solvent. In the same manner as in the examples, an ethanol reflux extract of Aguitake was prepared as a test material at 65 ° C. or higher.

<Experimental Example 1> Measurement of Pancreatic Cholesterol Esterase Activity Using Agaric Extract of the Present Invention Pancreatic cholesterol esterase plays a role of non-specifically recognizing each component having an acyl chain and separating the acyl chain. . In order to measure pancreatic cholesterol esterase activity by the extract of Aitake of Examples and Comparative Examples, cholesterol esterase derived from porcine pancreas produced by Sigma Chemical was used as an enzyme.

  Using the property that pancreatic cholesterol esterase decomposes a chromogenic substance (chromo-genetic substrate (p-nitrophenylbutyrate)), the activity change of enzyme was confirmed by a chromogenic reaction. The enzyme activity inhibition effect was measured by a change in absorbance at 405 nm using a microplate reader, calculated based on the 405 nm absorbance of the extract-untreated group, and expressed in%.

  It was confirmed how the activity of the enzyme was changed by the extracts of Examples and Comparative Examples, and as a result, it was confirmed that the water extract of the Example significantly reduced the activity of pancreatic cholesterol esterase.

  On the other hand, the 70% and 100% ethanol extract samples of the comparative example showed almost no effect of inhibiting pancreatic cholesterol esterase activity. The experimental results are shown in comparison with FIG.

<Experimental Example 2> Measurement of pancreatic cholesterol esterase activity according to the concentration of Aguitake water extract On the other hand, pancreatic cholesterol esterase activity according to the concentration of the water extract of Aguitake in Example was measured. The amount of agaric water extract to be treated with pancreatic cholesterol esterase is diluted to 1/5, 1/10, and 1/50 times based on the initial concentration of Agaritake powder at the time of extraction (1%). The inhibitory effects of pancreatic cholesterol esterase activity were compared, and the results are shown in FIG.

<Experimental Example 3> Measurement of pancreatic lipase activity based on the concentration of agaricus water extract Pancreatic lipase recognizes each substrate having an acyl chain in a non-specific manner and separates the acyl chain. In order to measure the pancreatic lipase activity according to the concentration of the water extract of Example, the lipase derived from porcine pancreas produced by Sigma Chemical was used as an enzyme.

  Using the property that pancreatic lipase decomposes a chromogenic substance (chromo-genetic substrate (p-nitrophenylbutyrate)), the activity change of enzyme was confirmed by a chromogenic reaction. The enzyme activity inhibition effect was measured by a change in absorbance at 405 nm using a microplate reader, calculated based on the 405 nm absorbance of the extract-untreated group, and expressed in%.

  It was measured how the activity of the enzyme changed depending on the concentration of the water extract of Example Aguitake, and as a result, the water extract of Example Agittake significantly reduced the activity of pancreatic lipase in a concentration-dependent manner. confirmed. The results are shown briefly in FIG.

<Experimental Example 4> Measurement of Cholesterol Absorption by Aguitake Water Extract of the Present Invention In order to confirm whether or not the water extract of Example Agittake which showed an inhibitory effect on cholesterol esterase activity was effective even at the individual level Cholesterol absorption was measured.

1% (w / v) sodium carboxymethylcellulose (CMC-Na), 1% (v / v) Tween 80 (cholesteroleate, Amersham, 100 μCi / ml) labeled with an isotope ( ³ H) Tween 80), and mixed with unlabeled cholesterol oleate, 0.1 mL was forcibly administered to the mouse via an oral sonde so that 1 μCi per individual was contained.

  At this time, control group mice (Balb / c male, 8 weeks old, body weight ˜25 g) were treated with orlistat 400 μg (20 mg / kg) for inhibiting cholesterol absorption, and experimental group mice (Balb / c male). , 8 weeks old, body weight ˜25 g), 20 mL of the water extract (10 mg / mL) of Aguitake in Example was concentrated and 0.1 mL was orally administered.

  Six hours later, the blood of the mouse was collected and plasma was obtained by centrifugation at 14,000 rpm for 10 minutes at 4 ° C., and the dose was measured using a liquid scintillator (Beta counter, Beckman LS1801). The control group is a group to which nothing is administered as a cholesterol absorption inhibitor. The dose of the control group was determined as 1, and the fat absorption was determined as a relative value when the dose of each experimental group was divided by the dose of the control group.

  The agaric water extract according to the present invention showed a remarkable fat absorption inhibitory effect similar to orlistat used in the control group. The results are shown in comparison with FIG. For reference, the control group in FIG. 4 is a blood collection result of a mouse not administered with anything as a cholesterol absorption inhibitor.

  Although the example of the various dosage forms which used the water extract of the agaric of this invention as an active ingredient was described below, the formulation of this invention is not limited to this.

Production Example 1 Manufacture of powder Aguitake water extract powder 20mg
Lactose 100mg
Talc 10mg
The above components were mixed and filled into an airtight cloth to produce a powder.

Production Example 2 Manufacture of tablet Aguitake water extract powder 10mg
Cornstarch 100mg
Lactose 100mg
Magnesium stearate 2mg
After mixing each of the above components, tablets were produced by tableting by a conventional tablet production method.

Production Example 3 Manufacture of capsules Aguitake water extract powder 10mg
Crystalline cellulose 3mg
Lactose 14.8mg
Magnesium stearate 0.2mg
The above ingredients were mixed by a conventional capsule manufacturing method and filled into gelatin capsules to prepare capsules.

Production Example 4 Manufacture of liquid preparation Aguitake water extract powder 20mg
Isomerized sugar 10g
Mannitol 5g
Appropriate amount of purified water Add each component to the purified water and dissolve it using the usual method for producing liquids. Add the appropriate amount of lemon flavor, mix the above ingredients, add purified water and add purified water to the whole. After adjusting the whole to 100 mL, the solution was filled into a brown bottle and sterilized to produce a liquid preparation.

Production Example 5 Manufacture of injection Amount of water extract of Aguitake 10mg
Mannitol 180mg
Sterile distilled water for injection 3000mg
Na ₂ HPO ₄ , 12H ₂ O 25 mg
Per ampoule (2 mL) by normal injection manufacturing method
Manufactured with the above component contents.

Production Example 6 Manufacture of health foods Aguitake water extract powder 1000mg
Vitamin mixture appropriate amount Vitamin A acetate 70μg
Vitamin E 1.0mg
Vitamin B1 0.13mg
Vitamin B2 0.15mg
Vitamin B6 0.5mg
Vitamin B12 0.2μg
Vitamin C 10mg
Biotin 10 μg
Nicotinamide 1.7mg
50 μg of folic acid
Calcium pantothenate 0.5mg
Appropriate amount of inorganic mixture Ferrous sulfate 1.75mg
Zinc oxide 0.82mg
Magnesium carbonate 25.3mg
Monobasic potassium phosphate 15mg
Dicalcium phosphate 55mg
Potassium citrate 90mg
Calcium carbonate 100mg
Magnesium chloride 24.8mg

  The composition ratio of the above-mentioned vitamin and mineral mixture was a composition suitable for relatively healthy foods in a preferred embodiment, but the blending ratio may be arbitrarily changed, depending on the normal method for producing health foods. After mixing the above ingredients, granules can be produced and used in the production of health food compositions by conventional methods.

Claims (8)

  A composition for preventing or treating dyslipidemia characterized by containing an aqueous extract of Agaricus as an active ingredient.   The composition according to claim 1, wherein the water extract is Aguitake extracted with water having a temperature of 20 to 60 ° C. for 12 to 36 hours.   The said water extract is a composition of Claim 1 which mixes and extracts 1-5 g of Aitake powder per 50 mL of water.   The composition according to claim 1, wherein the water extract of Agaricus comprises 0.01 to 30% by weight.   A pharmaceutical composition for preventing or treating dyslipidemia, comprising an aqueous extract of Aguitake as an active ingredient.   The pharmaceutical product according to claim 5, wherein the pharmaceutical composition is any one of powder, granule, tablet, suspension, emulsion, injection, or syrup.   An improved health functional supplement composition for dyslipidemia comprising a water extract of Aguitake as an active ingredient.   The improved health functional supplement for dyslipidemia according to claim 7, wherein the health supplement composition is any one of a food, a food additive, and a beverage.

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