KR101565964B1 - Composition Comprising Water Extracts from Pleurotus eryngii var. ferulea (Pf.). for Treating or Preventing hyperlipidemia - Google Patents

Abstract

The present invention relates to a composition for preventing or treating hyperlipidemia, which comprises water extract of Astragalus mushroom as an active ingredient, and a health functional food containing the same, wherein the water extract of Astragalus mushroom has an activity of raising cholesterol ester and an ability of neutral fat absorption, It has an excellent effect over the extract.

Description

(Composition Comprising Water Extracts from Pleurotus eryngii var. ferulea (Pf.). for Treating or Preventing hyperlipidemia}

The present invention relates to a pharmaceutical composition comprising a water extract of Astragalus mushroom, which can be used for prevention or treatment of hyperlipidemia, and a health supplement food composition.

Hyperlipidemia refers to a state of high fat in blood. Generally, hyperlipidemia is defined as total cholesterol greater than 240 mg / dl or triglycerides greater than 200 mg / dl. Hyperlipidemia is known to be a major cause of hypertension, myocardial infarction and stroke due to cholesterol cholesterol blocking blood vessels and inhibiting blood circulation. The number of patients with hyperlipidemia has also been increasing steadily, and the number of patients with hyperlipidemia is increasing rapidly, which is expected to lead to an increase in the number of patients with hyperlipidemia. There are many reports on the treatment and prevention of hyperlipidemia and prescription methods.

The cause of hyperlipidemia is due to genetic factors and metabolic disturbances, but colostrums accumulate in the blood even in other causes such as excessive calorie meals and obesity triggered by lack of exercise (Bray GA, Popkin BM .: Dietary fat intake dose affect obesity. Am. J Clin. Nutr 68: 1157-1173 (1998)). In particular, increased intake of high-fat diets due to westernized diets is believed to be the main reason for hyperlipemia. At present, there are active development of candidate efficacies such as cholesterol absorption inhibitors for the prevention or treatment of hyperlipidemia worldwide, and accordingly, there is a growing interest in an evaluation model of antihyperlipidemic efficacy.

Currently, statin drugs are widely used for the treatment of hyperlipidemia. This class of drugs is an HMG-CoA reductase inhibitor that has the effect of inhibiting cholesterol synthesis and lowering blood LDL-cholesterol. In addition, ezetimibe, niacin and bibrate preparations are mainly used. However, there is a possibility that side effects such as myalgia, constipation or digestive disorder and hepatic dysfunction are rarely observed when the drug is administered.

On the other hand, about 10,000 kinds of mushrooms are reported all over the world, and many studies have been conducted in developed countries such as Europe, America, and Japan in order to secure useful resources for microorganisms because of high value of edible and medicinal products. In particular, many studies have reported that physiologically active substances produced by mushrooms have various side effects such as toxicity, safe function of the immune system in the human body, anti-cancer effect, and metabolic regulation.

The present inventors have undertaken the present invention by repeatedly studying natural substances having little or no in vivo side effects and inhibiting the absorption of cholesterol in the body and having an effect of improving hyperlipemia.

The scientific name of the above mushroom is Pleurotus eryngii var. ferulea (Pf: P.ferulea) is a variant of the mushroom. The English name is Ferula Oyster Mushroom, which is interpreted as a mushroom of Aiuchi. In China, Baekryeong side (白 霊 side ears) is called. It is wild in the arid tree of Xinjiang province, which is a dry region of China. It is suitable for growing in spring and autumn in Korea because it is medium temperature of 8 ~ 20 degrees.

It is known as a medicinal plant which is effective in gastrointestinal diseases, it releases coughs and inflammation, releases toxins in human body medicine books, stops coughing, relieves inflammation, It is a highly functional mushroom that has been shown to be effective in systemic diseases.

The inventors of the present invention have intensively studied the inhibitors that inhibit the reabsorption of cholesterol and triglyceride in the small intestine or reduce the cholesterol in the blood while substituting drugs such as statin, , Especially the water extract of Astragalus mushroom, effectively inhibited the absorption of cholesterol and triglyceride in the blood and completed the present invention.

Accordingly, it is an object of the present invention to provide a composition containing a substance for inhibiting cholesterol and triglyceride absorption in the body, which hardly shows any side effects in vivo, and a medical composition and a health functional food containing the active ingredient as a preventive or therapeutic composition.

The above object of the present invention is attained by obtaining water extract of Astragalus mushroom and using it as a test material to verify and evaluate the effect of improving hyperlipemia.

The composition comprising the water extract of Astaxantha mushroom as an active ingredient of the present invention has an excellent effect that can be effectively used for preventing or treating hyperlipemia by inhibiting the absorption of cholesterol and triglyceride in the body.

FIG. 1 is a graph comparing the CEL activity inhibitory effects of the extract of Astragalus mushroom of the examples of the present invention and the comparative example.
FIG. 2 is a graph comparing CEL activities according to the concentration of the water extract of P. japonicus according to an embodiment of the present invention. FIG.
FIG. 3 is a graph showing a comparison of TGL activity according to the concentration of the water extract of avi mushroom according to an embodiment of the present invention.
FIG. 4 is a graph comparing the amounts of cholesterol absorption from blood of a digestive tract of orlistat, a water extract of Astragalus mushroom and a conventional fat inhibitor, according to an embodiment of the present invention.

The water extract of Astragalus mushroom may be one prepared by a conventional method for producing a plant extract. Most preferably, the above dried mushroom is cooled and dried at a temperature of 15 캜, followed by pulverization. Then, the residue is removed, and 0.1 to 20 g of the pulverized product per 100 ml of water is added. Most preferably, 1 to 5 g of pulverized product per 100 ml of the extraction solvent And then extracted. Hot air drying at 40 占 폚 or higher was not preferred. In addition, when the content of crushed mulberry crumbs is too small compared to the extraction solvent, the cholesterol absorption effect of mugwort mushroom is not sufficient, and when the amount of the crushed mulberry crumbs is excessively large relative to the amount of the extraction solvent, The cost is increased, which is not preferable from the viewpoint of productivity.

The extracting conditions of the mushroom are preferably mixed with water as an extracting solvent and then heated at a temperature of 20 to 60 DEG C for 12 to 36 hours, most preferably at a temperature of 30 to 40 DEG C for 20 to 24 hours .

When extracting at a low temperature of 20 ° C or less, a long time is required for extracting the effective extract components. When extracting at a high temperature of 60 ° C or higher, the activity is poor and it is not preferable. In particular, water extracts extracted with heat at 100 ° C for 15 minutes or more were not available because of no activity.

When the extraction time is shortened to 12 hours or less, the concentration of the effective ingredient to be extracted is low, and when the extraction is performed for a long time longer than 36 hours, the increase in concentration of the extraction effective ingredient with increasing extraction time is insufficient, I did.

The water extract of the sea tangle mushroom extracted by the above method is preferably filtered using a filter or the like, and then the filtrate is centrifuged to remove the precipitate and then concentrated or concentrated under reduced pressure, followed by lyophilization.

On the other hand, the content of the water extract of avium mushroom as an active ingredient in the above-mentioned embodiment of the composition for treating or preventing hyperlipidemia is preferably 0.01 to 30% by weight. When the content of the water extract of the active ingredient, mugwort, is less than 0.01% by weight, the effect of inhibiting cholesterol absorption in the body is insignificant. When the content is more than 30% by weight, the effect of increasing the inhibitory activity is insufficient. Preferably, the content of the water extract of sea urchin mushroom in the composition is 0.001 to 50% by weight, most preferably 0.1 to 30% by weight.

The present invention provides a medicament for preventing or treating hyperlipidemia, which comprises, as an active ingredient, a water extract of Astragalus mushroom contained in the composition according to an embodiment. Such a medicament containing the water extract of Astragalus mushroom as an active ingredient may further contain suitable carriers, excipients and diluents conventionally used in the production thereof.

Examples of carriers, excipients, and diluents that can be included in the medicament containing the water extract of the present invention as an active ingredient of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, , Gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The medicinal product containing the water extract of Astaxantha mushroom of the present invention as an active ingredient can be used as oral formulations such as powders, granules, tablets, suspensions, emulsions and syrups according to a conventional method.

The oral formulations are meant to include solid and liquid formulations for oral administration and solid formulations for oral administration may include tablets, pills, powders, granules, capsules and the like, For example, starch, calcium carbonate, sucrose or lactose, gelatin and the like in combination with at least one excipient.

In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of liquid formulations for oral use include suspensions, solutions, emulsions, and syrups. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweetening agents, have.

The preferred dosage of the pharmaceutical composition containing the water extract of Astragalus membranes of the present invention varies depending on the condition and body weight, degree of disease, drug form, route of administration, and duration, but can be appropriately selected by those skilled in the art. Preferably, the medicinal product containing the water extract of Astragalus membranaceus of the present invention as an active ingredient is administered at a daily adult standard (60 kg body weight) of 0.0001 to 100 mg / kg on the basis of the amount of water extract of Astragalus mushroom, 10 mg / kg. The number of administrations may be administered once a day or divided into several administrations. The dose and the number of administrations do not limit the scope of the present invention in any aspect.

According to another embodiment of the present invention, there is provided a health functional food for improving hyperlipidemia comprising an aqueous extract of Astragalus mushroom as an active ingredient. In the present specification, the term 'health functional food' means a natural product or a processed product containing one or more nutrients, preferably a state of being able to be directly eaten through a certain processing step.

Examples of the health functional food to which the water extract of the present invention can be added include various foods, beverages, gums, tea, vitamin complex, and the like. In addition, in the present invention, the food may contain special nutritional foods (e.g., crude oil, spirits, infant food, etc.), meat products, fish products, tofu, jelly, noodles (Such as soy sauce, soybean paste, hot pepper paste, mixed sauce), sauces, confectionery (eg snacks), dairy products (eg fermented milk, cheese), other processed foods, kimchi, pickled foods But are not limited to, fruits, vegetables, beverages, fermented beverages, etc.), natural seasonings (e.g., ramen soup, etc.). The food, beverage or food additive may be prepared by a conventional production method.

In the present specification, the functional food refers to a food group which is imparted with added value to function and express the function of the food by using physical, biochemical, biotechnological techniques, etc., Means a food which is processed and designed so that the body control function related to restoration and the like is sufficiently expressed to the living body. The functional food may include a food-acceptable food-aid additive, and may further comprise suitable carriers, excipients and diluents conventionally used in the production of functional foods.

In the present specification, beverage means a generic term for drinking or enjoying a taste and is intended to include a functional beverage. The beverage is not limited to any particular ingredient except that it contains the water extract of the mussel as an active ingredient as an essential ingredient at the indicated ratio and may contain various flavors or natural carbohydrates as an additional ingredient . Examples of such natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrins, cyclodextrins and the like, and Xylitol, sorbitol, and erythritol. Natural flavors (tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate may be generally about 1 to 20 g, preferably 5 to 12 g, per 100 mL of the composition of the present invention. In addition, the composition of the present invention may be used for the production of natural fruit juice, fruit juice drink, And may further contain flesh.

In addition to the above, the health functional food of the present invention may contain various kinds of nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate etc.), pectic acid and its salts, And salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, water, carbonating agents used in carbonated drinks, 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 present invention.

In the present specification, functional beverages are used to control the bio-defense rhythm of the beverage group or beverage composition to which the added value is imparted so that the function of the beverage functions for a specific purpose by using physical, biochemical, biotechnological techniques, Means a beverage which has been designed so that the body control function related to restoration and the like is sufficiently expressed in the living body.

The functional beverage is not particularly limited to the other ingredients except that it contains the water extract of the present invention as an essential ingredient in the indicated ratios and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary drinks have. Examples of such natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrins, cyclodextrins and the like, and xylitol , Sorbitol, and erythritol. Natural flavors (tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably 5 to 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 be 0.01 to 15% by weight of the total food, and the beverage composition may contain 0.02 to 5 g May be contained in a proportion of 0.3 to 1 g.

According to another embodiment of the present invention, there is provided a method for preparing the above water extract of Astragalus mushroom.

According to an embodiment of the present invention, there is provided a method for preparing a water extract of Acanthopanax senticosus, comprising: preparing powder of Acanthopanax senticosus; Mixing the avid mushroom powder with water; And extracting the mixture at a temperature of 20 to 60 DEG C for 12 to 36 hours.

Hereinafter, the structure and effects of the present invention will be described in more detail with reference to specific examples of the present invention. However, the following examples are only for the purpose of clarifying the invention, and the scope of the invention is not limited to the following examples.

However, for example, powder of Astragalus mushroom, which is devoid of the present invention, as a result of intensive and repeated experiments conducted by the present inventors, does not have an effect of inhibiting cholesterol ester raising activity, and thus does not fall within the scope of the present invention.

[ Example ] Mushroom  Water extract preparation

Dried mushroom (Pleurotus eryngii var. Ferulea (Pf.) Was purchased from the market and coarsely pulverized and put into a bag made of gauze. After mixing 50 ml of water with 1 g of powder as an extraction solvent, The supernatant of the shaking incubator was centrifuged at 2500 rpm for 10 minutes, and the supernatant was collected and used as a labeling material.

[ Comparative Example ] Mushroom  Water extract preparation

The ethanol reflux extract of the mushroom was disclosed 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 mL of 100% Materials were prepared.

< Experimental Example 1 > Invention Avi mushroom  Pancreatic cholesterol by extract Esther Reyes  Active measurement

Pancreatic cholesetester esterase plays a role in recognizing acyl chain - bearing substrates as non - specific and isolating acyl chains. In order to measure the pancreatic cholesterol ester raising activity by the extracts of Opuntia ficus-indica in the examples and the comparative examples, a poison flinic acid cholesterol ester raise made in a sigma chemical as an enzyme was used.

Pancreatic cholesterol esterase cleaved the chromo-genic substrate (p-nirophenylbutyrate) and the activity of the enzyme was confirmed by color reaction. The inhibitory effect of the enzyme was measured using a microplate reader at 405 nm and calculated as% based on the absorbance at 405 nm of the extract-untreated group.

The activity of the enzyme was measured by the extracts of Examples and Comparative Examples. As a result, it was confirmed that the water extract of the Example significantly reduced the activity of the pancreatic cholesterol ester raise.

On the other hand, in the 70% and 100% ethanol extract samples of the comparative example, the effect of inhibiting the activity of pancreatic cholesterol ester raise was hardly observed. The experimental results are briefly shown in comparison with FIG.

< Experimental Example 2 > Avi mushroom  Pancreatic cholesterol levels according to the concentration of water extract Esther Reyes  Active measurement

On the other hand, the pancreatic cholesterol ester raising activity was measured according to the concentration of water extract of Astaxanthana mushroom in the examples. When diluted with 1/5, 1 / 10th, and 1/50 of the initial concentration of avidin mushroom powder (1%) when extracting the amount of water-extracted mushroom water from pancreatic cholesterol esterase, The cholesterol esterase inhibitory activity was compared, and the results were shown in comparison with FIG.

< Experimental Example 3 > Avi mushroom  Measurement of pancreatic lipase activity by water extract concentration

Pancreatic lipase plays a role in recognizing acyl chain-bearing substrates nonspecifically and isolating acyl chains. Example To measure the activity of pancreatic lipase according to the concentration of water extract of avipura mushroom, poisin plate crytopic lipase prepared from Sigma chemical was used as an enzyme.

Pancreatic lipase degrades the chromo-genic substrate (p-nirophenylbutyrate) and the activity of the enzyme was confirmed by the color reaction. The inhibitory effect of the enzyme was measured using a microplate reader at 405 nm and calculated as% based on the absorbance at 405 nm of the extract-untreated group.

As a result, it was confirmed that the water extract of A. manganica extract of the Example significantly decreased the activity of pancreatic lipase in a concentration-dependent manner. The results are briefly shown in Fig.

< Experimental Example 4 > Invention Avi mushroom  Measurement of cholesterol absorption by water extract

Cholesterol absorption in the gastrointestinal tract was measured in order to determine whether the water extract of Astragalus membranaceus in the examples showing inhibition of cholesterol esterase activity was also effective at the individual level.

Cholesterol oleate labeled with isotope ( ³ H) (Amersham, 100 μCi / ml) was dissolved in 1% (w / v) sodium carboxymethyl cellulose (CMC-Na), 1% 80 (Tween 80), unlabeled cholesterol oleate, and 0.1 mL of the solution was orally administered to mice in an amount of 1 μCi per mouse.

At this time, 400 μg of Orlistat (20 mg / kg) of cholesterol absorption inhibitory effect was administered to the control mice (Balb / c male, 8 weeks old and weighing ~ 25 g) ), 20 mL of the water extract of Adi-mushroom (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 and centrifuged 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 is a group in which nothing is administered as a cholesterol absorption inhibitor. The dose of the control group was set to 1 and the dose of each experimental group was divided by the dose of the control group.

The water extract of P. falciparum according to the present invention showed remarkable fat absorption inhibitory effect like the olistat used as the control group. The results are shown in comparison with FIG. For reference, in FIG. 4, control is a blood sampling result of a mouse in which nothing is administered as a cholesterol absorption inhibitor.

Examples of various formulations containing the water extract of Astaxantha mushroom of the present invention as an active ingredient are described below, but the formulations of the present invention are not limited thereto.

Manufacturing example  One. Sanje  Produce

Artichoke 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

Ai 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

Ai 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

Artichoke mushroom water extract powder 20 mg

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added to purified water according to the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and then purified water was added thereto. The entirety was adjusted to 100 mL by adding purified water, To prepare a liquid agent.

Manufacturing example  5.  Injection preparation

Water extract of Ai mushroom 10mg

180 mg mannitol

Sterile sterilized water for injection 3000 mg

Na ₂ HPO ₄ , 12H ₂ O 25 mg

(2 mL) per ampoule according to the usual injection method,

It is prepared with the above ingredient contents.

Manufacturing example  6.  Manufacture of health food

1000 ㎎ of water extract powder of avi mushroom

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)

delete delete delete delete 1 ~ 5g of dried mushroom (Pleurotus eryngii var. Ferulea) which is dried and pulverized at 40 ° C or less is mixed with 100mL of water and the filtrate of the supernatant of water extract extracted at 20 ~ 60 ° C for 12 ~ 36 hours or its powder is contained as an active ingredient Or a pharmaceutically acceptable salt thereof. The pharmaceutical composition for preventing and treating hyperlipidemia according to claim 5, wherein the composition is any one selected from powders, granules, tablets, suspensions, emulsions, injections or syrups. 1 ~ 5g of dried mushroom (Pleurotus eryngii var. Ferulea) which is dried and pulverized at 40 ° C or less is mixed with 100mL of water and the filtrate of the supernatant of water extract extracted at 20 ~ 60 ° C for 12 ~ 36 hours or its powder is contained as an active ingredient Which is a functional food composition for preventing and improving hyperlipidemia. The composition according to claim 7, wherein the composition is a food, a food additive or a beverage.

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