KR20130066535A - Composition comprising water extracts from pleurotus eryngii var. ferulea (pf.). for treating or preventing hyperlipidemia - Google Patents

Abstract

PURPOSE: A composition containing a water extract of Pleurotus eryngii var. ferulea (Pf.) as an active ingredient is provided to suppress absorption of cholesterol and neutral fat in body, and to prevent or treat hyperlipidemia. CONSTITUTION: A composition for preventing or treating hyperlipidemia contains a water extract of Pleurotus eryngii var. ferulea (Pf.) as an active ingredient. The water extract is prepared by extracting Pleurotus eryngii var. ferulea (Pf.) at 20-60 deg. C for 12-36 hours. The extract is prepared from 1-5g of Pleurotus eryngii var. ferulea (Pf.) powder with 50 mL of water. A pharmaceutical composition for preventing or treating hyperlipidemia contains the water extract as an active ingredient. A health functional health food supplement composition for treating hyperlipidemia contains the water extract as an active ingredient. [Reference numerals] (AA) Cholesterol esterase activity

Description

Composition for the prevention or treatment of hyperlipidemia, containing water extract of agaric mushroom as active ingredient {Composition Comprising Water Extracts from Pleurotus eryngii var. ferulea (Pf.). for Treating or Preventing hyperlipidemia}

The present invention relates to a pharmaceutical composition and a dietary supplement composition comprising a water extract of Awi mushroom, which can be used for the purpose of preventing or treating hyperlipidemia.

Hyperlipidemia refers to a condition in which fat is high in blood. In general, it is called hyperlipidemia when total cholesterol exceeds 240mg / dl or triglyceride more than 200mg / dl. Hyperlipidemia is known to be a major cause of high blood pressure, myocardial infarction and stroke by clotting cholesterol and blocking blood circulation. The number of hyperlipidemia patients in Korea is also increasing steadily, and the increase of hyperlipidemia patients in the world is expected to lead to more hyperlipidemia patients. Many reports on the treatment, prevention and prescription of hyperlipidemia have been presented.

The cause of hyperlipidemia is a metabolic disorder caused by genetic factors, but it is also caused by the accumulation of cholesterol in the blood (Bray GA, Popkin BM .: Dietary fat intake) in other causes, such as obesity triggered by excessive calories and lack of exercise. dose affect obesity.Am. J Clin.Nutr 68: 1157-1173 (1998). In particular, the increased intake of high fat diets due to westernized diets is considered the main reason for hyperlipidemia. Currently, the development of candidate agonists such as cholesterol absorption inhibitors for the prevention or treatment of hyperlipidemia is being actively conducted worldwide, and accordingly, interest in the antihyperlipidemic efficacy evaluation model is increasing.

Currently, drugs for treating hyperlipidemia are widely used in statins. This class of drugs is an HMG-CoA reductase inhibitor that inhibits cholesterol synthesis and lowers blood LDL-cholesterol. In addition, ezetimibe, niacin, and fibrate are mainly used, but there are concerns that side effects such as muscle pain, constipation or digestive disorders and liver dysfunction may occur rarely when the drug is administered.

On the other hand, about 10,000 species of mushrooms are reported around the world, and because of their high edible and medicinal value, many studies have been conducted in developed countries such as Europe, the United States, and Japan in order to secure them as useful resources for microorganisms. In particular, many studies have reported that physiologically active substances produced by mushrooms are safe in terms of toxicity due to less side effects and have various functions such as regulation of immune system function, anticancer effect and metabolism in human body.

The inventors of the present invention have repeatedly studied the natural substance having almost no side effects in vivo and inhibiting cholesterol absorption in the body and improving hyperlipidemia.

It is a variant of Pleurotus eryngii var. It grows wild in Awi tree of Xinjiang province, which is the dry area of China.

Awi mushrooms, native to China and Central Asia, are known as medicinal plants that can relieve clogging, relieve coughs and inflammation, and are effective against gastrointestinal diseases.They release toxins, cough, relieve inflammation, and obstetrics and gynecology. It is a highly functional mushroom that has been shown to be effective against systemic diseases.

The inventors of the present invention as a natural substance that can replace a drug such as statin, while studying the inhibitor for inhibiting the reabsorption of cholesterol and triglycerides or reducing blood cholesterol in the small intestine, the extract of Awi mushroom In particular, it was confirmed that the water extract of Awi mushroom effectively inhibits the absorption of cholesterol and triglycerides in the blood and completed the present invention.

Accordingly, the present invention is to provide a composition comprising a water for inhibiting the absorption of cholesterol and triglycerides in the body almost without in vivo, and a prophylactic or therapeutic medical composition and a health functional food containing the same as an active ingredient.

The above object of the present invention was achieved by verifying and evaluating the effect of improving hyperlipidemia by obtaining a water extract of Awi mushroom and using it as a test material.

The composition comprising the water extract of Awi mushroom of the present invention as an active ingredient has an excellent effect that can be usefully used for the prevention or treatment of hyperlipidemia by inhibiting absorption of cholesterol and triglyceride in the body.

1 is a graph showing a comparison of the inhibitory effect of CEL activity of the extract of Awi mushrooms of Examples and Comparative Examples of the present invention.
Figure 2 is a graph showing a comparison of CEL activity according to the concentration of Awi mushroom water extract according to an embodiment of the present invention.
Figure 3 is a graph showing a comparison of TGL activity according to the concentration of Awi mushroom water extract according to an embodiment of the present invention.
Figure 4 is a graph showing a comparison of the amount of cholesterol absorption from the digestive tract of the water extract of Awi mushrooms according to an embodiment of the present invention and the conventional fat inhibitor orlistat from the digestive tract.

The water extract of Awi mushroom may be prepared according to the conventional method for producing a plant extract. Most preferably, the above-mentioned mushrooms are pulverized after cold and dry at 15 ° C., and then the residues are removed, and 0.1 to 20 g of the crushed powder is added per 100 mL of water, and most preferably 1 to 5 g of pulverized powder per 100 mL of the extraction solvent. Extract by adding. Hot air drying of 40 degreeC or more was not preferable. In addition, if the content of the crushed awi mushroom is too small compared to the extraction solvent, the cholesterol absorption effect of the awi mushroom is not sufficient, and if it is too large compared to the amount of the extraction solvent, the effect of increasing the content is not large. As the cost increases, it is not preferable in terms of productivity.

Extraction conditions of the above-mentioned mushrooms is preferably 20 to 24 hours at a temperature of 20 to 60 ℃, 12 to 36 hours, most preferably at a temperature of 30 to 40 ℃ after mixing the mushroom with water as the extraction solvent Should be extracted.

When the extraction is performed at a low temperature of 20 ° C. or less, a long time is required for the extraction of the effective extraction component, and when the extraction is performed at a high temperature of 60 ° C. or more, the activity is not preferable because of the extraction. In particular, the water extract obtained by hot water extraction for 15 minutes or more at 100 ℃ could not be used.

When the extraction time is shortened to 12 hours or less, the concentration of the active ingredient to be extracted is low, and when extracted for a long time of 36 hours or more, the increase in the concentration of the extraction active ingredient with the increase of the extraction time is insignificant, which is undesirable in terms of productivity. Did.

In addition, the water extract of Awi mushrooms extracted in the above manner was filtered through a filter cloth, etc., the filtrate was centrifuged to remove the precipitate, and then concentrated or concentrated under reduced pressure, and then preferably used by freeze drying.

On the other hand, the content of the water extract of Awi mushroom as an active ingredient in the treatment or prevention composition for hyperlipidemia of the above-described embodiment is preferably 0.01 to 30% by weight. When the content of the water extract of Awi mushroom as an active ingredient is less than 0.01% by weight, the effect of inhibiting cholesterol absorption in the body is insignificant, and when it exceeds 30% by weight, the effect of increasing the inhibitory activity by increasing the content is not economical. Preferably, the content of the water extract of Awi mushroom in the composition is 0.001 to 50% by weight, most preferably 0.1 to 30% by weight.

The present invention provides a pharmaceutical for the prevention or treatment of hyperlipidemia, comprising the water extract of Awi mushroom contained in the composition as an active ingredient. Medicines containing such a water extract of Awi mushroom as an active ingredient may further comprise suitable carriers, excipients and diluents commonly used in the preparation thereof.

Carriers, excipients, and diluents that may be included in a medicament comprising the water extract of Awi mushroom of the present invention as an active ingredient 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.

Medicines containing the water extract of Awi mushroom of the present invention as an active ingredient may be used in oral formulations such as powders, granules, tablets, suspensions, emulsions, syrups, etc. according to conventional methods.

The oral formulation is meant to include a solid preparation and a liquid preparation for oral administration, the solid preparation for oral administration may include tablets, pills, powders, granules, capsules, etc., such solid preparation is the extract At least one excipient, for example, may be prepared by mixing starch, calcium carbonate, sucrose or lactose, gelatin and the like.

In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral use include suspensions, solvents, emulsions, and serums.In addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. have.

Preferred dosages of the pharmaceutical compositions containing the water extracts of the above-mentioned mushrooms of the present invention vary depending on the condition and body weight, 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. Preferably, the drug containing the water extract of Awi mushroom of the present invention as an active ingredient is 0.0001 to 100 mg / kg per adult day (60 kg body weight) based on the amount of water extract of Awi mushroom, in order to be more effective 0.01 to Administration at 10 mg / kg is preferred. The number of administrations may be administered once per day or may be divided several times. The dosage and frequency of administration are not intended to limit the scope of the invention in any aspect.

According to another embodiment of the present invention, there is provided a health functional food for improving hyperlipidemia comprising water extract of Awi mushroom as an active ingredient. As used herein, the term "health functional food" means a natural product or a processed product containing one or more nutrients, and preferably means a state in which it can be directly eaten through some processing process.

Examples of health functional foods to which the water extract of Awi mushroom of the present invention can be added include various foods, beverages, gums, teas, vitamin complexes, and the like. In addition, the food in the present invention includes special nutritional products (e.g., prepared oils, infants, baby food, etc.), processed meat products, fish products, tofu, jelly, noodles (e.g. ramen, noodles, etc.), health supplements, seasoned foods ( For example, soy sauce, miso, red pepper paste, mixed soy sauce, sauces, confectionery (eg snacks), dairy products (eg fermented milk, cheese, etc.), other processed foods, kimchi, pickles (various kimchi, pickles, etc.), beverages ( Examples include, but are not limited to, fruits, vegetable drinks, soy milk, fermented beverages, and the like, and natural seasonings (eg, ramen soup). The food, beverage or food additive may be prepared by a conventional production method.

In the present specification, the functional food is a biological defense rhythm control, disease prevention and the like having a food group or food composition that has added value to the food by using physical, biochemical, biotechnological techniques, etc. to function and express the function of the food for a specific purpose. It means a food that is designed and processed to fully express the gymnastics function on recovery. The functional food may include food acceptable food additives, and may further include appropriate carriers, excipients and diluents commonly used in the manufacture of functional foods.

In the present specification, the beverage is a generic term for drinking to quench thirst or to enjoy a taste and is intended to include a functional beverage. The drink contains water extract of the above-mentioned mushroom as an active ingredient in the ratio indicated as an active ingredient, and there are no special limitations to the other ingredients, and it may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Can be. Examples of such natural carbohydrates include monosaccharides such as glucose, fructose and other disaccharides such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like, 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 ratio of the natural carbohydrate may generally be about 1 to 20 g, preferably 5 to 12 g per 100 mL of the composition of the present invention, in addition to the composition of the present invention for the production of natural fruit juices, fruit juice drinks, vegetable drinks It may further contain pulp.

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, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid And salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, water, carbonation agents used in carbonated beverages, and the like. These components can be used independently or in combination. The proportion of such additives is not so critical, but may be selected in the range of 0 to 20 parts by weight per 100 parts by weight of the water extract of the above mushroom.

In the present specification, the functional beverage refers to a biological defense rhythm control, disease prevention, and the like having a beverage group or a beverage composition which has added value to the beverage by using physical, biochemical, or biotechnological techniques to act and express the function of the beverage to a specific purpose. Means a beverage that is designed and processed to fully express the gymnastics function related to recovery.

The functional beverage is not particularly limited in addition to the water extract of the awi mushroom of the present invention 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 such natural carbohydrates include monosaccharides such as glucose, fructose and other disaccharides such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like, and xylitol Sugar alcohols such as 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 natural carbohydrates 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 hyperlipidemia, the amount of the extract may include 0.01 to 15% by weight of the total food weight, the beverage composition is 0.02 to 5 g, preferably based on 100 mL Preferably it may be included in a ratio of 0.3 to 1g.

On the other hand, the present invention provides a method for producing a water extract of the above mushroom according to another embodiment.

Method for producing a water extract of agaric mushroom according to an embodiment of the present invention comprises the steps of preparing a powder of agaric mushroom; Mixing the above mushroom powder with water; And extracting the mixture at a temperature of 20 to 60 ° C. for 12 to 36 hours.

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

However, the powder of the above-mentioned Awi mushrooms, for example, the present inventors concentrated and repeated experiments, as there is no inhibitory effect on cholesterol esterase activity will not belong to the scope of the present invention.

[ Example ] Awi mushroom  Water extract preparation

After purchasing dried dried Pleurotus eryngii var.ferulea (Pf.), Coarse powder into a gauze bag and mixing 50mL of water per 1g of powder with extraction solvent, and then at 37 ℃ for 24 hours The supernatant of the shaker was centrifuged at 2500 rpm for 10 minutes, and the filtered supernatant was collected and used as a test material.

[ Comparative example ] Awi mushroom  Water extract preparation

Exposed ethanol reflux extract of Awi mushrooms at 65 ° C. or higher in the same manner as in the above example, except that 70% of ethanol (99.9% (v / v)) and 100% of 100% were used instead of 50 mL of water as the extraction solvent. Prepared with the material.

< Experimental Example 1 > The present invention Avi mushroom  Pancreatic Cholesterol by Extracts Ester raise  Active measurement

Pancreatic cholesterol esterase is responsible for separating acyl chain by non-specific recognition of substrates with acyl chain. In order to measure pancreatic cholesterol esterase activity by Awi mushroom extracts of Examples and Comparative Examples, posin pancreatic cholesterol esterase prepared from Sigma Chemical was used as an enzyme.

Pancreatic cholesterol esterase was used to decompose the chromo-genic substrate (p-nirophenylbutyrate). The inhibitory effect of enzyme was measured by the change in absorbance of 405nm using a microplate reader, and calculated based on the 405nm absorbance of the extract untreated group and expressed as%.

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

On the other hand, the 70% and 100% ethanol extract samples of the comparative example showed little effect of inhibiting the activity of pancreatic cholesterol esterase. The experimental results are briefly shown in comparison with FIG. 1.

< Experimental Example 2 > Avi mushroom  Pancreatic Cholesterol According to the Concentration of Water Extracts Ester raise  Active measurement

On the other hand, pancreatic cholesterol esterase activity was measured according to the concentration of the water extract of Awi mushrooms of Examples. The amount of Awi mushroom water extract treated in the pancreatic cholesterol esterase is 1/5 times 1/10 times and 1/50 times dilution based on the initial awi mushroom powder concentration. Cholesterol esterase activity inhibitory effect was compared, and the results are shown in comparison with FIG.

< Experimental Example 3 > Avi mushroom  Measurement of Pancreatic Lipase Activity According to Concentration of Water Extract

Pancreatic lipase is responsible for separating acyl chain by non-specific recognition of substrates with acyl chain. Example In order to measure pancreatic lipase activity according to the concentration of Awi mushroom water extract, pocin pancreatic lipase prepared from Sigma Chemical was used as an enzyme.

Pancreatic lipase decomposed chromo-genic substrates (p-nirophenylbutyrate) to determine the changes in the activity of enzyme through color reaction. The inhibitory effect of enzyme was measured by the change in absorbance of 405nm using a microplate reader, and calculated based on the 405nm absorbance of the extract untreated group and expressed as%.

It was measured how the activity of the enzyme depends on the concentration of the extract of the water extract of Example, and as a result, it was confirmed that the activity of the pancreatic lipase significantly reduced the activity of the extract of the extract of Example. The results are briefly shown in FIG.

< Experimental Example 4 > The present invention Avi mushroom  Determination of Cholesterol Absorption by Water Extracts

Cholesterol uptake in the digestive tract was measured to determine whether the Awi mushroom water extract of the example showed the effect of inhibiting cholesterol esterase activity.

Isotope ( ³ H) labeled cholesterol oleate (Cholesterol oleate, Amersham, 100 μCi / ml) in 1% (w / v) carboxymethylcellulose sodium (CMC-Na), 1% (v / v) twin Twenty-eighty (Tween 80) mixed with unlabeled cholesterol oleate was forced to dose 0.1 mL via oral maximal administration to mice to contain 1 μCi per subject.

At this time, control mice (Balb / c male, 8 weeks old, weight ~ 25g) to 400 μg (20mg / kg) of Orlistat of cholesterol absorption inhibitory effect, experimental mice (Balb / c male, 8 weeks old, weight ~ 25g) ), 20 mL of the Awi mushroom water extract (10 mg / mL) of the example was concentrated and 0.1 mL was orally administered.

After 6 hours, the blood of the mice was collected, the plasma was obtained by centrifugation at 14000 rpm for 10 minutes at 4 ° C, and the dose was measured using a liquid scintillator (Beta counter, Beckman LS1801). The control group was administered with no cholesterol absorption inhibitors. The dose of the control group was set to 1, and the fat absorption amount was determined as a relative value when the dose of each experimental group was divided by the dose of the control group.

The water extract of Awi mushrooms according to the present invention showed a significant fat absorption inhibitory effect like the olistat used as a control. The results are shown in comparison with FIG. 4. For reference, in FIG. 4, the control is the blood sampling result of the mice not administered with the cholesterol absorption inhibitor.

Hereinafter, examples of various formulations using the water extract of Awi mushroom of the present invention as an active ingredient are described, but the formulation of the present invention is not limited thereto.

Manufacturing example  One. Sanje  Produce

Agaric Mushroom Water Extract Powder 20 mg

Lactose 100 mg

Talc 10 mg

The above ingredients were mixed and filled in an airtight container to prepare powders.

Manufacturing example  2. Manufacture of tablets

A. Mushroom Water Extract Powder 10 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

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

Manufacturing example  3.  Preparation of capsules

A. Mushroom Water Extract Powder 10 mg

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

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

Manufacturing example  4. Liquid  Produce

Agaric Mushroom Water Extract Powder 20 mg

10 g per isomer

5 g mannitol

Purified water quantity

According to the conventional method of preparing a liquid solution, each component is added to the purified water to dissolve, the lemon flavor is added appropriately, the above components are mixed, purified water is added, the whole is adjusted to 100 mL by adding purified water, and then filled into a brown bottle and sterilized. To prepare a liquid formulation.

Manufacturing example  5.  Injection preparation

Awi Mushroom Water Extract 10mg

Mannitol 180mg

3000mg sterile distilled water for injection

Na ₂ HPO ₄ , 12H ₂ O 25 mg

Per ampoule (2 mL) according to the usual method of preparation of injectables

It is prepared by the above ingredient content.

Manufacturing example  6.  Manufacture of health food

Agaric Mushroom Water Extract Powder 1000mg

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.

Claims (8)

A composition for the prevention or treatment of hyperlipidemia, characterized in that the content of water extract of Awi mushroom as an active ingredient. The method of claim 1,
The water extract is a composition characterized in that the extract of Awi mushrooms in water of 20 to 60 ℃ temperature, for 12 to 36 hours. The method of claim 1,
The water extract is a composition that is extracted by mixing 1 to 5g of awi mushroom powder per 50mL of water. The method of claim 1,
Water extract of the above mushroom composition comprising 0.01 to 30% by weight. A pharmaceutical composition for the prevention or treatment of hyperlipidemia, containing water extract of Awi mushroom as an active ingredient. 6. The pharmaceutical product according to claim 5, wherein the pharmaceutical composition is any one of a powder, a granule, a tablet, a suspension, an emulsion, an injection, or a syrup. A functional health supplement food composition for improving hyperlipidemia containing water extract of Awi mushroom as an active ingredient. 8. The improved functional dietary supplement for hyperlipidemia according to claim 7, wherein the dietary supplement composition is any one of food, food additive or beverage.

Images