JPH11152230A - Composition containing mushroom or its extract - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a mushroom treatment product which gives sufficient and fixed effects even in the oral administration and can be utilized as a medicine or a health food capable of inexpensively producing. SOLUTION: This mushroom treatment product comprises at least two kinds of dry substances of mushrooms selected from the group consisting of Lentinus edodes, Pleurotus ostreatus, Pholiota nameko, Grifola frondosa, Flammulina velutipes and Tricholoma shimeji or their extracts extracted with water or a lower alcohol.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an effective use of edible mushrooms among basidiomycetes, and more particularly, to Lenti mushrooms.
nus edodes (Berk.) Sing.], Oyster mushroom [Pleurotus ostr
eatus (Jacq. exFr.) Quel.], Nameko [Pholiota nameko
(T.Ito) S.Ito et Imai], Maitake [Grifola frondos
a], Enokitake [Flammulina velutipes (Curt. ex Fr.)
Sing.] And Bunashimeji [Hypsizigus marmoreus], comprising a dried product of mushrooms or a mixture of extracts thereof, which can be used as a pharmaceutical or health food. .

[0002]

2. Description of the Related Art The research by the present inventors started,
It has become known that mushrooms have various physiological functions, for example, an immunopotentiating action, a blood pressure and blood sugar lowering action, an antioxidant action, etc., as it is or as an extract, as a drug for adult diseases or a health food. Widely used.

[0003] Although the physiologically active components of these mushrooms are shown to be polysaccharide glucans, purified pure glucans are not absorbed by oral administration, and exhibit their effects only by injection. Therefore, for oral administration, purified glucan was not used, and it was necessary to take the drug in the form of a glycoprotein in which a peptide was bound to glucan.

However, when these glycoproteins are taken orally, the peptides are decomposed in the stomach to produce glucan, and the amount of glycoprotein absorbed in the intestine is reduced. In addition, since the composition of mushroom glycoproteins currently taken differs depending on the type of raw material mushrooms and the method of collecting the mushrooms, the obtained effects are not only uniform, but the effects may be difficult to appear. The effect of the administration was not always satisfactory.

[0005] The present inventors have studied for a long time an efficient oral ingestion method of mushroom components. As a result, by formulating a conventionally used oral mushroom extract into enteric-coated tablets, glycoproteins in the stomach can be obtained. It was found that it can prevent the decomposition of sulphate and increase the absorption in the intestine. However, making enteric coated tablets is not a costly and economic method.

[0006]

Accordingly, there has been a demand for the development of a mushroom-treated product which can provide a sufficient and constant effect even by oral administration and can be produced at low cost. This is the subject of the present invention.

[0007]

Means for Solving the Problems The inventors of the present invention have conducted continuous studies to increase the absorption of glycoproteins derived from mushrooms by a simpler method. As a result, several types of dried mushrooms or their water or lower alcohols were obtained. It has been found that the use of an extract in a mixed manner results in a synergistic increase in absorption by oral ingestion, leading to the completion of the present invention.

That is, the present invention provides a composition comprising at least two types of dried mushrooms selected from the group consisting of shiitake mushrooms, oyster mushrooms, nameko, maitake, enokitake mushrooms and bunashimeji, or a water or lower alcohol extract thereof. About things.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The mushrooms used in the present invention, that is, shiitake mushroom, oyster mushroom, nameko mushroom, maitake mushroom, enokitake mushroom, and bunashimeji are all distributed in large quantities as edible mushrooms on the market. Although artificial mushroom cultivation methods have been established for these mushrooms, the present invention is not limited to natural mushrooms, and commercially available artificial cultivation products can be suitably used. Since artificially cultivated products have constant quality and specifications, the content and type of glycoprotein as an active ingredient are stable, and can be used more advantageously than natural mushrooms from the viewpoint of availability and economy. .

The dried product of the mushrooms used in the present invention is obtained by drying the mushrooms by a conventional method such as sun drying or hot air drying, and pulverizing and pulverizing the mushrooms as necessary. In addition, water or lower alcohol extract of mushrooms (hereinafter simply referred to as "extract")
Can also be prepared by a commonly used method. For example,
Add an appropriate amount of water or lower alcohol to the mushroom or its dried product, heat it as necessary, extract it under non-reflux or under reflux, separate the extract from the solid, and distill off the extraction solvent under reduced pressure. The extract may be removed and removed. In the case of water, the extraction temperature is preferably 90 ° C. or more, particularly preferably about 95 ° C. The lower alcohol used for the extraction means an alcohol having 1 to 4 carbon atoms, specifically, methanol, ethanol,
Examples are propanol and butanol. The extract may be in the form of an extract, but is preferably in a dry state from the viewpoint of storage stability and the like.

[0011] The composition of the present invention is prepared by using shiitake mushroom, oyster mushroom,
It is carried out by mixing at least two types of dried or extracted mushrooms selected from the group consisting of nameko, maitake, enokitake and bunashimeji. The extract is usually prepared for each type of mushroom, but two or more types of mushrooms or a dried product thereof are mixed at a predetermined ratio in advance, and the mixture is extracted and extracted with the above-mentioned solvent. It may be an inventive composition.

In the present invention, the combination of dried mushrooms and extracts is, for example, a combination of two kinds of mushrooms, such as shiitake mushroom and oyster mushroom, and a combination of three kinds of mushrooms such as shiitake mushroom, oyster mushroom and nameko. Or a combination of four to five mushrooms, a combination of all six mushrooms, and the like.

The mixing ratio of these dried products or extracts is not particularly limited, and can be selected according to the type and purpose of the mushroom. For example, in the case of a combination of two mushrooms, the weight ratio of the dried product or extract is preferably in the range of 7: 3 to 3: 7, more preferably in the range of 4: 6 to 6: 4. Desirably, the blending amount of each is around 50%, that is, the weight ratio is around 1: 1. In the case of a combination of three or more types of mushrooms, the mixing ratio can be appropriately determined according to the purpose. However, in the case of four combinations of enokitake, bunashimeji, shiitake, and maitake, the weight ratio of each is 4:
The ratio is preferably about 4: 1: 1 or 3: 3: 3: 1.

Among the combinations of mushrooms in the present invention, the most preferable combination is, for example, a composition comprising a combination of enokitake and bunashimeji, enokitake and shiitake, or bunashimeji and shiitake mushroom in a weight ratio of 1: 1. The synergistic effect is remarkable as shown in Examples below.

In the present invention, a dried or extracted mushroom treated with a suitable enzyme, for example, a glycolytic enzyme such as amylase or glucanase, may be used.

The composition of the present invention may be used as a powder in the form of the above-mentioned dried product or extract as it is. For example, it is used after processing into tablets, capsules, granules, liquids, and other commonly manufactured preparations. In addition, commonly used additives such as excipients can be used for the formulation thereof. Particularly in the case of tablets, the most desirable dosage form as a mushroom preparation can be obtained by film coating for the purpose of preventing moisture absorption. The tablet film coating can be performed according to a conventional method (for example, “Latest Pharmaceutical Science”, page 211, Hirokawa Shoten; and “Recent Formulation Technology and Its Application II”, page 91, Pharmaceutical Journal Co., Ltd.). Ed., Etc.).

Further, when formulating the composition of the present invention,
As long as the effects of the present invention are not impaired, synthetic or natural additives such as sweeteners, coloring agents, flavors, and the like may be blended, and Ganoderma licidum (Ganoderma licidum (F
r.) Krast.], Phellinus linteus (Berk. e
t Curt) Aoshima], and other mushroom-derived components such as dry powder or extract of mushrooms of the family Sarcodonaceae.

In order to exert the intended effect of the present invention, the oral intake varies depending on the age, weight, purpose, etc. of a person.
There is no particular limitation. However, it is considered appropriate to take the mushroom extract in the range of 200 mg to 5000 mg, preferably 1000 mg to 3000 mg per day for adults in several divided doses.

[0019]

As described above, simple glucan, which is an edible mushroom component, does not show its effect by oral administration, and must be injected. In order to obtain a sufficient effect by oral administration, it is better to use mushroom water or a lower alcohol extract as it is, and it is clarified that the active ingredient in this case is a glycoprotein in which a peptide is bound to glucan. Have been. When these glycoproteins are taken orally, peptides are decomposed in the stomach to produce glucan, and the amount of glycoprotein absorbed in the intestine decreases. In addition, the amount of absorption during oral administration differs depending on the type of mushroom and its extract used, and it is considered that the effect is not constant.

On the other hand, although the mechanism of action of the present invention, that is, the reason that various physiological effects inherent in mushrooms are synergistically exerted by mixing two or more mushrooms, is not yet clear, It is presumed that the absorption is improved by the interaction of various glycoproteins contained in more than one species of mushrooms, or the synergistic effect is exhibited between several types of glycoproteins, although the absorption itself does not change .

[0021]

The present invention will be described below by way of examples with reference to the antitumor properties of mushroom extracts, but the present invention is not limited to these examples. That is, it is clear that the effects of the present invention are not limited to antitumor properties, but can be said for all physiological uses of the mushrooms described above.
The present invention is not limited to the mushroom extract, and even if a mixture of the mushroom itself is used, it is clear that the object of the present invention can be achieved, although the amount used is increased. Therefore, the present invention also includes a dry mixture of the mushroom itself,
The result of our research.

Example 1 2 L of purified water was added to 1 kg of Enokitake mushroom fruit body, and the mixture was extracted while heating under reflux for 2 hours to obtain an extract. This operation was repeated twice more, the extracts were combined, the solvent was distilled off under reduced pressure, and the obtained extract was freeze-dried to obtain 170 g of Enokitake mushroom extract, which was pulverized.

Similarly, 2 kg of purified water was added to 1 kg of the fruit body of Bunashimeji and extracted while heating and refluxing for 2 hours.
The extract was separated and concentrated. Repeat this three times in total,
They were combined and concentrated to a small amount under reduced pressure, and then lyophilized to obtain 150 g of Bunashimeji extract, which was pulverized.

Each of the resulting fine powder extracts was
Each g was mixed thoroughly and 200 g of the extracted mixture was obtained. This extract mixture (200 mg) was mixed well with lactose (140 mg), corn starch (60 mg), low-substituted hydroxypropylcellulose (15 mg) and magnesium stearate (3 mg) as excipients, and tableted.
It was immersed in keratin solution under cocoa butter, dried and film-coated to make tablets.

Example 2 2 L of water was added to 1 kg of Shiitake mushroom, and the mixture was heated and extracted. The extracted extract was separated.
g, and after fine pulverization, an equal amount of the fine powder of the mixed and extracted mixture obtained in Example 1 was added thereto and mixed well to obtain a mixed extract of three types. To this was added excipients as shown in Example 1,
Tablets were prepared by film coating using Eudragit (manufactured by Rohm and Haas).

Example 3 A dried substance of Enokitake mushroom body and a fine powder of dried substance of Bunashimeji body were mixed in the same amount, respectively, and 50 g thereof was suspended in 300 mL of a phosphate buffer to prepare Sample 1. Amylase (2500 units) was added to Sample 1 and reacted at 37 ° C. for 24 hours to prepare Sample 2. The anticancer test was performed on the samples 1 and 2 thus adjusted.

Eighteen ICR female mice of 5 weeks of age were subcutaneously implanted with 1 × 10 ⁶ to 10 ⁷ sarcoma ascites tumors / mouse subcutaneously in the flank. From the day after transplantation, the control group was treated with purified water, and the treated group was treated with the above sample 1 or 2 for 1500 m each.
The dose was orally administered once a day for 20 days at a dose of g / kg. Five weeks after the cancer transplantation, solid cancer was excised and its average weight was measured. In the group treated with the above sample, the sample 1 exhibited 51% inhibition of tumor growth, and the sample 2 exhibited 63% inhibition.

Example 4 Using the enokitake mushroom extract, Bunashimeji extract and a mixture thereof obtained in Example 1, the following anticancer test was carried out. As a group of 6 5-week-old ICR female mice, a control group and a treatment group were divided into approximately 1 × 1 ascitic tumor of sarcoma 180.
0 porting ⁶ cells / mouse in the flank subcutaneously in all mice. From the day after transplantation, the control group received physiological saline 10 times a day.
The test group was intraperitoneally administered for one day, and each of the treatment groups was suspended in physiological saline at a rate of 10, 30, and 100 mg / kg, respectively, for the enokitake mushroom extract, Bunashimeji extract and a mixture thereof.
It was administered once a day for 10 days. After 5 weeks, the solid cancer was excised and the average weight of the treated group was compared with that of the control group. The results are shown in Table 1.

[0029]

[Table 1] 率 Tumor growth inhibition rate ─────── ───────────────────────── Dose (mg / kg) 10 30 100 ─────────────── ───────────────── (Sample) Enokitake mushroom extract 63% 89% 100% Bunashimeji extract 65% 90% 100% Extract mixture 76% 100% 100% ─── ─────────────────────────────

Example 5 Using the same sample as in Example 4, a 5-week-old ICR female mouse was
A sarcoma 180 solid tumor was similarly transplanted, and samples were 500 mg / kg and 300 mg / kg, respectively, from the day after transplantation.
Each of them was orally administered once a day for 10 days, and after 5 weeks, a solid tumor was excised, and the average weight was compared with that of a control group. Table 2 shows the obtained results.

[0031]

[Table 2] 率 Tumor growth inhibition rate ─────────── ──────────────────── Dose (mg / kg) 300 500 ───────────────────── ────────── (Sample) Enokitake mushroom extract 17% 25% Bunashimeji extract 20% 23% Extract mixture 27% 32% ──────────────── ───────────────

Example 6 An extract obtained by mixing the enokitake mushroom extract obtained in Example 1 and the Shiitake mushroom extract obtained in Example 2 at a ratio of 1: 1 was subjected to an anticancer test in the same manner as in Example 4. Was done. Table 3 shows the results.

[0033]

[Table 3] 率 Tumor growth inhibition rate ──────── ─────────────────────── Dose (mg / kg) 10 30 100 ───────────────── ────────────── (Sample) Shiitake mushroom extract 60% 87% 100% Enokitake mushroom extract 63% 89% 100% Extract mixture 73% 94% 100% ────── ─────────────────────────

Example 7 1 kg of Oyster mushroom was immersed in 2 L of purified water, heated and extracted for 2 hours, and treated in the same manner as in Example 1 to obtain Oyster mushroom extract 1
55 g were obtained. The Oyster mushroom extract obtained here and the Bunashimeji extract obtained in Example 1 were mixed at a ratio of 1: 1 to prepare an extraction mixture. Example 1 was added to the obtained extraction mixture.
Was added to prepare a film-coated tablet.

Example 8 The extracted mixture of Oyster mushroom and Bunashimejiji obtained in Example 7 was subjected to an anticancer test in the same manner as in Example 4. Table 4 shows the results.

[0036]

[Table 4] 率 Tumor growth inhibition rate ──────── ─────────────────────── Dose (mg / kg) 10 30 100 ─────────────────試 (Sample) Bunashimeji extract 65% 90% 100% Oyster mushroom extract 55% 80% 97% Extract mixture 70% 93% 100% ────────────── ─────────────────────────

Example 9 2 L of purified water was added to 1 kg of Maitake, and the mixture was heated and extracted for 2 hours, and treated in the same manner as in Example 1 to obtain 135 g of Maitake extract. The mushroom extract was prepared by mixing the Enokitake mushroom extract, Bunashimeji extract obtained in Example 1 and Shiitake mushroom extract obtained in Example 2 with the mixture. The weight ratio is Enokitake 35, Bunashimeji 35, Shiitake 15,
The ratio of Maitake 15 was used. The excipient shown in Example 1 was added to the obtained extract mixture, and the mixture was filled in a capsule to prepare a capsule. Similarly, an excipient was added to the extracted mixture, and the mixture was tableted and coated with a film to protect from moisture to prepare tablets.

Example 10 The mushroom extract prepared in Example 9 was subjected to an anticancer test in the same manner as in Example 4. Table 5 shows the results.

[0039]

[Table 5] Tumor growth inhibition rate ──────── ─────────────────────── Dose (mg / kg) 10 30 100 ───────────────── ────────────── (Sample) Shiitake extract 60% 87% 100% Maitake extract 55% 80% 100% Enokitake extract 63% 89% 100% Bunashimeji extract 65% 90% 100% Four kinds of mushrooms 86% 99% 100% Extract 剤

Example 11 Immunity Enhancing Action: Mouse leukemia cell L-1210 was added to 0.0
Treated with 13% glutaraldehyde-phosphate buffer solution
Thereafter, the cells are further treated with concanavalin A,
A-ConA-L-1210 cells were prepared. This cell
Mouse BDF₁1 × 10 for female ⁶Intraperitoneal injection of mice / mouse
Fired.

One week after the first injection, a second injection was given. The next day, the following mixtures A and B were prepared and administered using the enokitake mushroom extract, Bunashimeji extract and the mixed extract prepared in Example 1. That is, a mixture of 50% of Enokitake mushroom extract to 50% of Bunashimeji extract (A) and a mixture of 45% of Enokitake mushroom extract to 55% of Bunashimeji extract (B) were added to each group of mice for 500 minutes.
Oral administration was performed in mg / kg. Six days after the administration of the drug, 1 × 10 ² living cells of L-1210 / mouse were transplanted intraperitoneally into all the mice, and the immunostimulatory activity was measured by the average number of days of survival of the mice. The results are shown in Table 6.

[0042]

[Table 6] 用 Immunity boosting action 免試 料 Sample mean survival time Survival rate ─────────────────────────── Control group 13 days-Enokitake mushroom extract 15 days 15.4% Bunashimeji extraction Product 16 days 23.0% Extract mixture (A) 18 days 38.5% Extract mixture (B) 18 days 38.5% ──────

Example 12 2 L of ethanol was added to 10 kg of Enokitake mushroom fruit bodies, and the mixture was heated under reflux for 1 hour, and then the solvent was distilled off from the extract under reduced pressure. This extraction operation was repeated twice to obtain 12 g of Enokitake mushroom ethanol extract. On the other hand, 10 kg of Bunashimeji fruit extract was similarly extracted twice with ethanol to obtain 10 g of Bunashimeji ethanol extract. These two extracts were directly mixed and a tablet was prepared in the same manner as in Example 1.

Example 13 As in Example 11, vaccine for L-1210
Was administered intraperitoneally to BFD female mice. Twice a day
And administered one week apart. 1 × 10 cells ⁶Pieces / ma
Was used. And Enokitake mushroom ethanol extract 100
mg / kg, Bunashimeji ethanol extract 100 mg /
kg and each ethanol extract 1 to 1 (weight)
100mg / kg each of the extracted mixture
It was administered intraperitoneally. On day 6 after drug administration, L-121
0 live cells 1 × 10²Peritone / mouse to all mice
Transplanted into. Table 7 shows the average survival days at that time.

[0045]

[Table 7] 用 Immunity boosting action 免───── Sample survival days Survival rate ─────────────────────────────── Control group 12.5 days-Enokitake Ethanol extract 14 days 12% Bunashimeji ethanol extract 13.5 days 8% Extract mixture 15 days 20% ─────────────────────────── ────

Although the mechanism of action is not clear, the effect of the mixed extract according to the present invention clearly shows a synergistic effect as compared with the effect of the single extract as shown in the above Examples.

[0047]

The mushroom extract mixture according to the present invention exhibits a synergistic effect as compared with a single mushroom extract and enhances its effect.
It is useful for prevention and treatment of adult diseases such as hypertension, hyperlipidemia, angina pectoris, myocardial infarction, diabetes and allergic diseases and obesity, and is widely effective in preventing and treating lifestyle-related diseases. . that's all

Claims (6)

[Claims] 1. A composition comprising a dried product of at least two types of mushrooms selected from the group consisting of shiitake, oyster mushroom, nameko, maitake, enokitake, and bunashimeji, or a water or lower alcohol extract thereof. 2. The composition according to claim 1, wherein two mushrooms are used, and the weight ratio of the dried product or the water or lower alcohol extract is in the range of 3: 7 to 7: 3. 3. The composition according to claim 1, wherein the mushrooms are enokitake and bunashimeji. 4. The composition according to claim 1, which is for oral administration. 5. The composition according to claim 4, wherein the dosage form is a powder, tablet, capsule, granule or liquid. 6. The composition according to claim 5, wherein the tablet is a film-coated tablet.