JPH11269088A - Blood lipid-reducing agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject reducing agent, such as a cholesterol-reducing agent, having an action for reducing the content of lipids in blood by including Hericium erinaceum and/or its preparation as an active ingredient. SOLUTION: This blood lipid-reducing agent contains a kind of mushroom, Hericium erinaceum, and/or its preparation, preferably the residue of the ethanol extract of the Hericium erinaceum, as an active ingredient. The preparation of the Hericium erinaceum is obtained, for example, by finely cutting the fruit bodies of the Hericium erinaceum, extracting the finely cut product with an extraction solvent such as ethanol at 10-40 deg.C for 12-36 hr, if necessary, with stirring, subjecting the obtained treatment product to a filtration or centrifugal treatment to remove the extraction solvent, and subsequently taking out the insoluble contents.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a blood lipid lowering agent, and more particularly, to a blood lipid lowering agent excellent in blood lipid lowering effect which contains Yamabushitake and / or a preparation thereof as an active ingredient.

[0002]

2. Description of the Related Art Heretofore, there have been several reports on compounds contained in mushroom cultures and fruiting bodies and their drug effects. Among them, Yamabushitake, a mushroom belonging to the family Agaricaceae, showed that the octadecenoic acid derivative, isoindolinone derivative, and phthalide derivative contained in the fruit body had a cell killing effect on cervical cancer cells.
No. 157347, JP-A-3-15767, and JP-A-3-157379.

[0003] Similarly, fruit bodies, cultured mycelia of Yamabushitake,
Reports that polysaccharides contained in a culture solution have high antitumor activity (JP-A-5-117303, JP-A-5-117303)
-117304 publication). The benzyl alcohol derivative and chroman derivative in the fruiting body are PGE
Its use as a ₂ (prostaglandin E ₂ ) production inhibitor and NGF (nerve growth factor) production inducer is reported in Japanese Patent Publication No. 7-72157, Japanese Patent Publication No. 8-26010 and the like.

Furthermore, it has been disclosed in Japanese Patent Application Laid-Open Nos. Hei 6-256352, Hei 6-256378 and Hei 7 that the cyanate derivative in cultured mycelium can be used as an NGF (nerve growth factor) production inducer or antibacterial agent. -69961, JP-A-7-70133, JP-A-7-701
No. 68, JP-A-8-73486 and the like.

However, there has been no report on the other drug effects of Yamabushitake other than those described above, and research on new drug effects of Yamabushitake and the development of new uses of Yamabushitake therefrom have been expected.

[0006]

SUMMARY OF THE INVENTION The present invention has been made in view of the above, and an object of the present invention is to provide a novel use of Yamabushitake.

[0007]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, it has been found that Yamabushitake and / or its preparation, in particular, the ethanol extraction residue of Yamabushitake has a high lipid content in blood. Have been found to have the effect of lowering the pressure, and the present invention has been completed.

[0008] That is, the present invention relates to Yamabushitake and / or
Or a blood lipid lowering agent containing the preparation as an active ingredient. As a preparation of Yamabushitake used as an active ingredient in the blood lipid-lowering agent of the present invention, specifically,
Examples of the extract include Yamabushitake ethanol extraction residue obtained as an insoluble solid content separately from the extract when Yamabushitake is extracted with ethanol.

[0009] Specific examples of the blood lipid lowering agent of the present invention include a cholesterol lowering agent. Here, in the present specification, "having a blood lipid lowering effect"
The term is used to mean that it has one or both of an action of lowering the blood lipid level and an action of suppressing an increase in the blood lipid level.

[0010]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.
First, Yamabushitake and / or a preparation thereof containing the blood lipid-lowering agent of the present invention will be described.

(1) Yamabushitake and / or preparation thereof used in the present invention The blood lipid lowering agent of the present invention contains Yamabushitake and / or a preparation thereof. The term “Yamabushitake” used in the present invention refers to the family Agaricaceae (Hydnaceae), the genus Coral agaricus (H
ericium, which is a kind of mushroom belonging to Heliciumerinaceum. In addition, the Yamabushitake used in the present invention includes a fruit body of Yamabushitake and the like.

[0012] The fruit body of Yamabushitake is obtained by cultivating Yamabushitake by a usual method. In the present invention, it is also possible to use wild products of the fruit bodies of Yamabushitake. Furthermore, since the fruiting body of Yamabushitake is sold in Japan and abroad, it can be used in the present invention.

The fruit body of Yamabushitake thus obtained contains a substance having an action of lowering the amount of blood lipid, and the fruit body may be used as it is in the present invention. It is preferable that these are treated by an appropriate method to form a preparation containing the substance having a blood lipid-lowering effect, which is then incorporated into the blood lipid-lowering agent of the present invention. Specific examples of the preparation include preparations obtained by combining one or more of general processes such as crushing, pulverization, grinding, squeezing, extraction, fractionation, concentration, and drying.

Preferably, the preparation used in the present invention is an alcohol of Yamabushitake obtained as an insoluble solid content separately from the extract when Yamabushitake is extracted with an alcohol-based extraction solvent such as ethanol, methanol or propanol. System solvent extraction residue and the like can be mentioned. Among the alcohol-based extraction solvents used for obtaining the extraction residue of Yamabushitake, ethanol is preferably used in the present invention.

The extraction process of Yamabushitake with the alcohol-based extraction solvent can be performed by a continuous method, a batch method, or the like, and by a general method, by immersion or cold soaking for an arbitrary time. For example, after shredding the fruiting body of the above-mentioned Yamabushitake, the extraction solvent is added at 10 to 40 ° C.
For example, a method of performing an extraction treatment with stirring for up to 36 hours as needed. The alcohol-based solvent extraction residue of Yamabushitake used in the present invention is obtained by removing the extract from the treated product obtained by the above-mentioned extraction treatment by filtration or centrifugation, and taking out the insoluble solids. The obtained insoluble solid content can be used as it is in the present invention as an extraction residue, but it is also possible to remove the extraction solvent from the insoluble solid content under reduced pressure or the like to dry it, or to completely remove water by freeze-drying. Or a treatment obtained by combining these drying treatments, may be pulverized as necessary and used as an extraction residue.

Next, the blood lipid lowering agent of the present invention containing the above-mentioned Yamabushitake and / or its preparation will be described.

(2) Blood lipid lowering agent of the present invention The blood lipid lowering agent of the present invention comprises the above-mentioned Yamabushitake and / or
Or the preparation is contained as an active ingredient. The blood lipid-lowering agent of the present invention contains the above-mentioned Yamabushitake and / or its preparation, and thereby has an effect of lowering the amount of lipids in blood, specifically, the amount of cholesterol, triglyceride, phospholipid, and the like. Have. Also, the effect of the blood lipid lowering agent of the present invention can be expected to be particularly effective in lowering the blood cholesterol level.

The blood lipid-lowering agent of the present invention may be composed only of the active ingredient Yamabushitake and / or a preparation thereof, or may contain various carriers as constituents in consideration of the dosage form and the like. . Here, the dosage form of the blood lipid lowering agent of the present invention is not particularly limited.

Further, the blood lipid-lowering agent of the present invention is further combined with various optional components within a range that does not impair the effects of the present invention in accordance with various uses, and has a composition, for example, a blood lipid-lowering effect. It can be a pharmaceutical composition, a food composition, or the like. In addition, in these compositions, a pharmaceutically active ingredient having a hypolipidemic effect other than the hypolipidemic agent of the present invention can be blended together with the hypolipidemic agent of the present invention.

When a pharmaceutical composition is prepared using the blood lipid-lowering agent of the present invention, the above-mentioned optional components are generally one of a pharmaceutically acceptable inorganic or organic compound, or several kinds of vehicles, carriers, and additives. Excipients, disintegrants, binders, lubricants, preservatives, stabilizers, wetting agents, emulsifying / solubilizing / dispersing agents, pH adjusters, isotonic agents, sweetening agents, fragrances, coloring agents, etc. Can be. The dosage form of the pharmaceutical composition is not particularly limited, but the composition is determined by the administration route, administration schedule, etc., for example, powders, granules, tablets, capsules, suspensions, emulsions,
It can be formulated into various dosage forms that are usually used, such as liquid preparations, using conventionally known techniques. Examples of the administration form include oral administration and the like.

Specifically, when a solid preparation is produced, a binder such as corn starch and gelatin, an excipient such as calcium carbonate and microcrystalline cellulose, a starch, Dispersing agents such as sodium carboxymethylcellulose, lubricants such as talc, lactose, powdered tablets by dispensing sweeteners such as sucrose, etc.,
Granules, tablets and capsules can be prepared. Also,
In the case of liquid preparations such as emulsions, suspensions, and liquid preparations, generally used inert diluents such as water and vegetable oil can be used as carriers. Liquid preparations include, in addition to the above inert diluents, wetting agents, emulsifying / solubilizing / dispersing agents,
H adjusters, isotonic agents, sweeteners, coloring agents, preservatives, stabilizers and the like may be added. Further, such a liquid preparation can be formulated by containing it in a capsule made of an absorbable substance such as gelatin.

When a food composition is prepared using the blood lipid-lowering agent of the present invention, the blood lipid-lowering agent of the present invention comprises
It can be blended with various foods together with optional ingredients commonly used in foods. Examples of such food compositions include confectionery such as crackers, cakes, cookies, and jellies, juices, vegetable drinks, drinks such as alcoholic beverages, staple foods such as bread, sauces, seasonings such as ketchup, and the like. Can be

The above-mentioned food composition also includes various forms usually used as health foods and health drinks, for example, powders, granules, tablets, capsules, liquids and the like. Is used together with the blood lipid-lowering agent of the present invention, such as various excipients, binders, disintegrants, lubricants, flavoring agents, bulking agents, coating agents, etc., and is usually used for formulating health foods and health drinks. It is possible to mix the desired components in any amount, and they are manufactured by the same manufacturing method as that for manufacturing the above-mentioned preparations generally except that the blood lipid lowering agent of the present invention is added as an active ingredient. be able to.

The blood lipid-lowering agent of the present invention or a composition containing the same, such as a pharmaceutical composition or a food composition, is produced by the action of the active ingredient Yamabushitake and / or its preparation. Since it has the effect of lowering the amount of lipids in the blood, particularly the amount of cholesterol, various diseases known to be induced by the presence of excess lipids in the blood, such as prevention of arteriosclerosis and the like It can be used for treatment.

[0025]

Embodiments of the present invention will be described below.

[0026]

Example 1 Production of Blood Lipid-Lowering Agent 20 kg of viable fruiting bodies of Yamabushitake was roughly crushed using a food processor. Next, the obtained crude crushed product was immersed in 40 L of ethanol, and subjected to an extraction treatment at 20 ° C. for 24 hours.
The mixture was separated into an extract and an extraction residue by filtration. The obtained extraction residue was subjected to an evaporator to remove residual ethanol, and then lyophilized to completely remove water. This dried residue was crushed and powdered using a mill mixer. The obtained powder was directly used as a blood lipid lowering agent.

[0027]

Example 2 Evaluation of Blood Lipid-Lowering Agent The change in the amount of lipid in the blood of the experimental animal when the feed containing the blood lipid-lowering agent obtained in Example 1 above was ingested by the experimental animal was described below. The blood lipid-lowering agent of the present invention was evaluated by examining the method according to the above method.

(1) Preparation of Feed As a control feed, a feed having a composition shown in the control feed column of Table 1 was used. As a test feed, a corn starch of the control feed having a composition shown in the test feed column of Table 1 was prepared. A feed partially replaced with the blood lipid lowering agent obtained in Example 1 above,
Each was prepared and used for the experiment.

[0029]

[Table 1] In Table 1, the mineral mixture (AIN-76) and the vitamin mixture (AIN-76) are a mineral composition and a vitamin composition, respectively, manufactured by Oriental Yeast Co., Ltd.

(2) Breeding experiments As test animals, 18 Wistar rats (4 weeks old, male, Japan SLC, Inc.) were used. Said 1
Eight rats were preliminarily reared for 4 to 5 days using a preliminarily reared feed in which all of the sucrose in the control feed was replaced with corn starch as a feed, and then these were randomly fed to a control feed administered group 10 And the test feed administration group was divided into 8 groups.

After the completion of the preliminary breeding, the feed was switched to the two types of feed obtained in the above (1), that is, the control feed was administered to the control feed, and the test feed was administered to the test feed. The animals were bred for 2 weeks. In addition,
In the entire breeding period including the preliminary breeding period, all the experimental animals had a temperature of 24 ± 1 ° C., a humidity of 50 to 60%,
Lighting / dark cycle; 1 hour in an environment set for 12 hours
They were bred at a rate of one per gauge. In addition, water and feed intake was free during the entire breeding period.

During the above two-week breeding period,
Body weight and food intake were measured for each rat. Body weight after preliminary breeding / before main breeding start, body weight after main breeding end (two weeks after main breeding start), weight gain in two week main breeding,
Table 2 shows the feed intake for two weeks of this rearing as the average value of each group together with the standard deviation.

[0033]

[Table 2]

From the above results, it was confirmed that there was no difference between the control feed administration group and the test feed administration group with respect to the feed intake and the increase in body weight.

(3) Evaluation of Blood Lipid-Lowering Effect On the 14th day from the start of the main breeding, the breeding was terminated and blood was collected from each rat. That is, from the cut part obtained by beating the rat with a cutting scissors after beating and fainting,
Blood was collected in a centrifuge to which 50 units of heparin had been added in advance. The collected blood was collected at 3000 rpm for 20 minutes.
The mixture was centrifuged at 5 ° C for 5 minutes to obtain plasma as a supernatant. The obtained plasma was stored at −20 ° C. until subjected to the following lipid amount measurement.

The amount of lipid contained in plasma obtained as described above was determined using a commercially available measurement kit. That is, the total cholesterol amount was determined using a cholesterol test C-Wako (manufactured by Wako Pure Chemical Industries, Ltd.). ) For the amount of triglyceride, triglyceride G-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.), and for the amount of phospholipid,
Phospholipid C-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.)
HDL-cholesterol-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.)
Was measured using each. Also, VLDL-LD
L cholesterol is calculated from total cholesterol in HDL
It was determined by subtracting the cholesterol level. The results are shown in Table 3 as the average value of each group together with the standard deviation. The unit of each lipid amount is mg / 100 ml.

Further, a significant difference test of the lipid amount of the test feed administration group with respect to the lipid amount of the control feed administration group was carried out. Analysis (ANOVA) was performed and the results were determined using the modified Tukey's method as a post-hoc test. The results of the significant difference test are shown by an asterisk superscript on the right side of the lipid amount of the test feed administration group in Table 3. Asterisk 2
Individual ( ^** ) means that a significant difference is recognized at p <0.01.

[0038]

[Table 3]

From these results, the amount of lipids in the plasma of the test feed-administered group bred by ingesting the test feed containing the blood lipid-lowering agent obtained in Example 1 was determined by the blood lipid-lowering agent of the present invention. There was a tendency for all the lipids measured above to be lower than the amount of lipid in the plasma of the control diet-administered group bred by ingesting the control diet containing no. In particular, it is clear that the amount of cholesterol and the amount of phospholipid are significantly less in the test feed group than in the control feed group.

[0040]

The present invention provides, as a novel use of Yamabushitake, a blood lipid-lowering agent containing the same, and the blood lipid-lowering agent reduces the amount of lipids in blood, especially cholesterol. Has the effect of lowering.

Claims (3)

[Claims] 1. A blood lipid-lowering agent containing Yamabushitake and / or a preparation thereof as an active ingredient. 2. The blood lipid lowering agent according to claim 1, wherein the preparation of Yamabushitake is an ethanol extraction residue of Yamabushitake. 3. The blood lipid lowering agent according to claim 1, wherein the blood lipid is cholesterol.