JP2009024027A - Physiologically active composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a physiologically active composition comprising a plurality of components originating from herbal medicines, and exhibiting various physiological activity. <P>SOLUTION: The composition consists of β-glucan and one or two or more kind of amino acids selected from the group consisting of arginine, leucine, valine, alanine, glycine, proline, glutamic acid, serine, threonin and aspartic acid. The composition further comprises a protein having 24,000 Da-29,000 Da molecular weight by SDS polyacrylamide gel slab electrophoresis. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention has antitumor activity, antihyperlipidemic activity, blood pressure lowering activity, blood glucose level lowering activity and the like, has a low risk of side effects, and contributes to the maintenance and improvement of QOL (Quoality of life). A bioactive composition is provided. In particular, the present invention relates to a composition that can be used as a therapeutic or prophylactic agent for hypercholesterolemia, etc. in addition to an antitumor composition, and in particular, a composition having a lowering action such as total cholesterol and / or LDL cholesterol. About. The present invention also relates to a composition effective as a drug for treating or preventing hyperlipidemia in diabetic patients. Furthermore, the present invention relates to a composition having a health promoting action.

  Various herbal medicines such as fruit bodies of fungi belonging to the basidiomycete Sarnococcidae and medicinal carrots have been used for a long time. However, the relationship between these ingredients and medicinal properties is still unclear. In addition, in these crude drugs, it is estimated that multiple ingredients contained in the crude drug act synergistically, but since many ingredients are contained in the crude drug, such multiple ingredients are identified. It was difficult to do.

  Therefore, an object of the present invention is to provide a physiologically active composition containing a plurality of components derived from herbal medicines and capable of exhibiting various physiological activities.

The present inventor has found that anti-tumor activity, anti-hyperlipidemic activity, blood pressure lowering activity, blood glucose level lowering activity and the like synergistically increase when a plurality of herbal medicines are blended. Moreover, when using a specific kind of crude drug, it discovered that various high physiological activity was shown. And paying attention to these common components, the present invention was completed. That is, according to the present invention, the following means are provided.
(1) containing one or more amino acids selected from the group consisting of arginine, leucine, valine, alanine, glycine, proline, glutamic acid, serine, threonine, and aspartic acid, and β-glucan, Bioactive composition.
(2) The composition according to (1), wherein the amino acids are arginine, alanine, glutamic acid, and aspartic acid.
(3) The composition according to (1) or (2), further comprising a protein having a molecular weight of 2,4000 Da to 2,9000 Da as determined by SDS polyacrylamide gel slab electrophoresis.
(4) The composition according to any one of (1) to (3), further containing ergosterol.
(5) The composition according to any one of (1) to (4), further comprising one or more metals selected from the group consisting of potassium, magnesium, zinc, and manganese.
(6) A physiologically active composition containing one or more amino acids selected from the group consisting of arginine, lysine, histidine, phenylalanine, alanine, and glutamine.
(7) The composition according to (6), further comprising a protein having a molecular weight of 2,4000 Da to 2,9000 Da by SDS polyacrylamide gel slab electrophoresis.
(8) The composition according to (6) or (7), further comprising one or more metals selected from the group consisting of potassium, magnesium, zinc, and manganese.

  Hereinafter, embodiments of the present invention will be described in detail. The first composition of the present invention comprises one or more amino acids selected from the group consisting of arginine, leucine, valine, alanine, glycine, proline, glutamic acid, serine, threonine, and aspartic acid, and β- Glucan. And have. In addition, the second composition of the present invention contains one or more amino acids selected from the group consisting of arginine, lysine, histidine, phenylalanine, alanine, and glutamic acid.

  The composition of this invention is specified based on the component extracted from the component contained in the extract from one or more types of basidiomycete belonging to the basidiomycete family Sarnosidaceae and the roots of the plant belonging to the family Argiaceae. Moreover, the other composition of this invention is specified based on the component extracted from the component contained in the extract from only the root of the plant which belongs to the family Argiaceae. Therefore, a part or the whole of the present composition is obtained by adopting basidiomycetes and roots of Argiaceae as raw materials of these compositions and obtaining an extract obtained by extracting them with an appropriate extraction solvent. It is possible to obtain However, the acquisition method of this composition is not limited to this, The compound which can be obtained commercially also corresponding to each of these components can also be mix | blended. In addition, it is preferable to employ β-glucan and ergosterol from these extracts, including proteins.

  Although the form of this composition is not specifically limited, Preferably it is the form of a solution. The solvent is water and / or alcohol. In the case of a water / alcohol mixed solution, the alcohol content is preferably 35 vol% or less, more preferably 20 vol% or less, still more preferably 10 vol% or less, and most preferably 5 vol% or less. Further, it does not exclude the inclusion of components other than those specified in the composition of the present invention, carbohydrates (including monosaccharides, disaccharides, oligosaccharides and polysaccharides), lipids and plant fibers. Absent. These components can be contained within a range that does not substantially affect the action of the composition of the present invention. Moreover, when eating and drinking as a dietary supplement and a nutritional supplement, it is preferable to contain a sugar or lipid having an appropriate energy imparting property.

  Hereinafter, each component will be described. In addition, although the density | concentration of each component is shown with the quantity per 100 g of solution, the ratio of the density | concentration of each of these components can be employ | adopted as a composition ratio of a component as it is.

  The first composition contains one or more amino acids selected from the group consisting of arginine, leucine, valine, alanine, glycine, proline, glutamic acid, serine, threonine, and aspartic acid. However, it is preferable that at least arginine, glutamic acid and aspartic acid are included. More preferably, in addition to these three types, further contains alanine. Most preferably, it contains all. Arginine is preferably 3 to 30 mg, alanine is preferably 1 to 5 mg (preferably 2 mg or more), glutamic acid is preferably 3 to 15 mg, and aspartic acid is 3 to 15 mg. Preferably there is. Such an amino acid composition is preferably obtained by extracting the fruiting bodies of basidiomycetes belonging to the family Basidiomycetes and the roots of the family Argiaceae with water and / or alcohol. A specific extraction method will be described later.

  The second composition has one or more amino acids selected from the group consisting of arginine, lysine, histidine, phenylalanine, alanine and glutamic acid, preferably arginine, lysine, Has histidine and glutamic acid. More preferably, in addition, phenylalanine and glutamic acid are contained. Arginine is preferably 10 to 100 mg, lysine is preferably 1 to 5 mg, histidine is preferably 1 to 5 mg, and glutamic acid is preferably 5 to 20 mg. Such an amino acid composition is preferably obtained by extracting the roots of Araceae plants with water and / or alcohol. A specific extraction method will be described later.

In addition, the various amino acids in the said composition can be measured by a conventionally well-known method. For example, the content can be measured by an amino acid automatic analysis method generally used for food analysis.

  Both the first and second compositions can contain a protein having a molecular weight of 2,4000 Da to 2,9000 Da as determined by SDS polyacrylamide gel slab electrophoresis. This protein can be confirmed, for example, by the following operation. That is, 1 l of water was added to 30 g of chiketsu carrot, heated and extracted for 90 minutes, and 1 l of a 35 v / v% alcohol solution was added to 30 g of chikutsu carrot, and 30 ° C. at 30 ° C. After 100 hours of heating, 100 ml of a solution, which was finally adjusted to 1 liter with water, was added to a sample preparation buffer solution [0.002%] after removing low molecular components by dialysis and then lyophilized. Bromophenol blue, 2% SDS, 50 mmol Tris-HCl buffer (pH 6.5) containing 2% SDS, 5% mercaptoethanol and 10% glycerol] so that the concentration is 5%. Use a sample for electrophoresis. SDS polyacrylamide gel slab electrophoresis is performed on a molecular weight region of 14 to 55 kDa, and protein components can be confirmed by Coomassie brilliant blue staining. As a comparative protein, MW-SDS-70L (Sigma Chemical Co.) can be used.

  The protein is preferably obtained by extracting with water and / or alcohol a root of the family Argiaceae, or a mixture of the root of the family Argiaceae and the fruiting body of a basidiomycete belonging to the family Basidiomycetes Sarnococcidae. . A specific extraction method will be described later. In particular, proteins extracted from medicinal carrots, particularly chixet carrots, with water and / or alcohol are preferred.

  The first and second compositions preferably contain one or more metals selected from the group consisting of sodium, phosphorus, calcium, potassium, magnesium, zinc, and manganese. More preferably, 2 types or 3 types or more are contained among these. In particular, it is preferable to contain at least one of potassium, magnesium, zinc, and manganese. It is preferable to contain manganese or zinc in addition to this, and more preferably all of potassium, magnesium, zinc, and manganese. Sodium is preferably 0.5 to 2.0 mg, phosphorus is preferably 2.6 to 20 mg (more preferably 3 to 15 mg), and calcium is 1.0 to 5. It is preferably 0 mg (more preferably 3.0 mg or less), potassium is preferably 10 to 40 mg (more preferably 30 mg or less), and magnesium is 0.5 to 5.0 mg (more preferably 3 mg). 0.0 mg or less), zinc is preferably contained in an amount of 5 μg to 50 μg, more preferably 5 to 25 μg, and manganese is preferably 10 μg to 250 μg, more preferably 150 μg or less. And / or 25 μg or more. These metals can be measured by various conventionally known methods. For example, the content can be measured by an atomic absorption method generally used for food analysis. The above metal composition is preferably obtained by extracting the fruit body of a basidiomycete belonging to the family Basidiomycetes and / or the roots of the family Araceae with water and / or alcohol. A specific extraction method will be described later.

  The first composition may further contain ergosterol. Ergosterol is preferably contained in an amount of 0.05 mg or more. More preferably, it contains 0.10 mg or more. The upper limit is not particularly limited, but is 1 mg or 0.4 mg. Ergosterol can be measured by a conventionally known method. For example, the content can be measured by a liquid chromatography method generally used for food analysis. Ergosterol is preferably obtained by extracting the fruiting body of a basidiomycete belonging to the family Basidiomycetes, or in addition to this, the roots of the family Argiaceae with water and / or alcohol. A specific extraction method will be described later.

  The first composition can also contain β-glucans. It is preferable to contain 0.01 g or more of β-glucans. More preferably, it is 0.05 g or more. Moreover, although an upper limit is not specifically limited, It can be 5 g or less. Moreover, Preferably it is 3 g or less, More preferably, it is 2 g or less. β-glucan can be measured by a conventionally known method. For example, the content can be measured by an enzyme method generally used for food analysis. The β-glucan is preferably obtained by extracting the fruiting body of a basidiomycete belonging to the family Basidiomycetes and / or the roots of the family Argiaceae with water and / or alcohol. A specific extraction method will be described later.

  The first and second compositions can also be produced by blending the above-described components. For example, some or all of the components may be a part of the basidiomycete Sarnococcidae. And a fruit body and / or mycelium culture of a basidiomycete belonging to Kawaratake, and a root of the family Argiaceae can be obtained by extraction with water and / or alcohol, respectively.

(Basidiomycetes-derived active ingredient)
As basidiomycetes, it is preferable to use at least Mannentake and Kawaratake. Particularly preferably, only Mannentake and Kawaratake are used. In the present specification, the taxonomic identification of basidiomycetes used is based on “Primary Color Japanese Fungi Encyclopedia” (Nuryosha Co., Ltd.) co-authored by Rokuya Imazeki and Tsuguo Hongo. The basidiomycetes may be naturally occurring, may be artificially cultivated, or may be cell culture, and are not particularly limited. Preferably, it is naturally occurring.

  The basidiomycete belonging to the mannentake is not particularly limited. Various kinds of mannambo can be used alone or in combination of two or more. Reishi Fungus (Ganoderma Lucidum) can be exemplified as a preferred mushroom. Although this fungus naturally thrives on trees, it is rare. Artificial cultivation is also possible. This bacterium has a glossy, wax-like bulk portion and a shaft portion, and the length of the shaft reaches about 15 cm. The fruit body colors are red, blue, yellow, white, purple, and black. This fungus grows on stumps and near the base of trees that are weakened by disease, forming white filaments. Furthermore, Ganoderma pheifferi and Ganoderma lipsiense can be used as other preferred mushrooms. Either one or both can be used. It can also be used in combination with litchi.

  Moreover, it is not specifically limited as Kawaratake. Various kinds of Kawaratake can be used alone or in combination of two or more. An example of a preferable bamboo shoot is Coriolus Versicolor. This fungus grows naturally in the western part of Japan, especially in the Shinshu region (especially Nagano Prefecture), Shikoku region, and Kyushu region. This fungus is naturally a good fungus, and particularly prefers hardwood. As another preferred Kawaratake, Trametes hirsutus can be used.

  The form of these fungi used in the present invention may be fruit bodies and / or cell cultures, but is preferably fruit bodies. The fruit body is preferably air-dried by avoiding light at room temperature. In particular, it is preferable to use a natural and mature black fruit body in the garlic mushroom. In the case of Kawaratake, it is preferably a native fruit body collected in summer, and more preferably air-dried avoiding light at room temperature. In addition, the fruiting body can be processed into a dried solid substance, an alcohol immersion liquid, a paste or an extract, in addition to those not particularly processed after collection, and can be obtained in these forms.

  In the composition of this invention, it is preferable to use 1 type (s) and 2 or more types among the above-mentioned specific types of Mannentake and Kawaratake. For example, it is preferable to use litchi as garlic mushroom and Coriolus Versicolor as kawaratake.

  A part of the components of the composition of the present invention can be obtained as an extraction component obtained by extracting the fruiting bodies of the above basidiomycetes or their cultures using water and / or alcohol.

(Acquisition method of active ingredient derived from basidiomycetes)
At the time of extraction, it is preferable to pulverize the fruiting bodies of basidiomycetes to form powders or strips. More preferably, it is in the form of fragments of about 7 mm square or less, and more preferably in the form of strips of about 4 mm to about 6 mm square. Most preferably, it is in the form of a strip of about 5 mm. A strip shape of 0.5 mm to 2 mm square may be preferable. When using mycelium cells as a raw material, it is preferable to use a dry powder.

  The basidiomycete-derived component is preferably extracted from the basidiomycete-derived raw material by a water: alcohol mixture in addition to water. When extracting with water, the water to be used is not particularly limited, but it is preferable to heat the extraction. Preferably, it is about 80-100 degreeC, More preferably, it is about 90-95 degreeC. Further, the amount of water relative to the extraction raw material is not particularly limited, but is about 5 to about 25 parts by weight of the dried raw material (more preferably about 10 to about 20 parts by weight, more preferably about 12 to about 15 parts by weight). Part), the amount of water for extraction is preferably set so that the amount of water after extraction is about 200 to 800 parts by weight (preferably about 500 to 700 parts by weight). This is because when the final extract is prepared in this concentration range, it is a concentration preferable for oral administration as it is, and effective extraction is performed.

  When the heat extraction operation is performed in a state that allows a reduction due to the evaporation of moisture, the initial amount of extraction water is set assuming a reduction in moisture during that time. For example, the amount of water is extracted by increasing it by about 50 to 60% with respect to the desired final amount of water. On the other hand, when the heat extraction operation is performed in a state where a reduction due to evaporation of moisture is not allowed, the extraction water amount to be finally obtained may be added to the raw material from the beginning and heated. Preferably, a reflux condenser is used.

  For the heating extraction operation, an open-air container or a reflux condenser can be used. In particular, in order to inhibit the extraction of the active ingredient and maintain the effectiveness of the extracted ingredient, it is preferable to use a material obtained by painting or processing a metal part with a corrosion-resistant coating, in addition to glass, enamel, or ceramic.

  Although the extraction time is not particularly limited, it is preferably at least 1 hour, more preferably 1.5 hours or more, and further preferably 2.5 hours or more. The upper limit is 3 to 4 hours.

  The following operation can be mentioned as a typical example in the case of extracting a basidiomycete raw material with water. Add about 800 g of hot water to about 20 g of the dried basidiomycetous raw material (preferably fruit bodies, preferably in the form of strips), and maintain the extract residue while maintaining at 90-95 ° C. Decoct to a volume of about 200 to about 700 ml. Preferably, the heating adjustment is performed so that the amount becomes about 200 ml to about 700 ml in about 1.5 to 3 hours. Alternatively, about 200 ml to about 700 ml of water is added to about 20 g and boiled for about 2 hours using a reflux condenser. The extract obtained by such an operation becomes a liquid having a concentration suitable for oral administration as it is.

  In the case of extracting with alcohol, it is preferable that the alcohol to be used is a drinkable alcohol in consideration of the case where it may be drunk as it is. That is, it is preferable to use ethanol. When extracting using alcohol, you may extract only with alcohol, However, It is preferable to mix with water and to extract with a liquid mixture. The alcohol concentration is preferably 50 v / v%, more preferably about 35 v / v%. The alcohol-containing extract is not particularly limited, but is preferably heated during extraction. Preferably, it is 50-80 degreeC, More preferably, it is 75 degreeC or less, More preferably, it is 70 degreeC or less. Although the extraction time is not particularly limited, it is preferably 10 hours or longer, more preferably 20 hours or longer, and most preferably about 30 hours or longer. It should be noted that the alcohol concentration is preferably about 20 v / v% or less at the final oral administration. Therefore, when extracted with an alcohol solution having a concentration exceeding 20 v / v%, it is preferable to dilute with water after extraction so as to be 20 v / v% or less. Further, the amount of the extraction liquid with respect to the extraction raw material is not particularly limited, but is finally about 50 to 250 parts by weight of the raw material, more preferably 100 to 200 parts by weight, and further preferably about 120 to 150 parts by weight. It is preferable to use 1000 parts by weight of the extract. The extract obtained by such an operation becomes a liquid having a concentration suitable for oral administration as it is. It is preferable to use the same container as that used for extraction with water alone. The extraction operation is preferably performed using a reflux condenser.

  In addition, when extracting using alcohol, the component which is not extracted only with water will be extracted. The ethanol-containing extract of basidiomycetes contains triterpenoids, nucleosides (adenosine, guanosine), and polysaccharides such as hetero-β-glucan, xylo-β-glucan, and manno-β-glucan.

  The following operation can be mentioned as a typical example in the case of extracting a basidiomycetous raw material with a water / alcohol mixture. To about 120-200 g of basidiomycetous raw material (preferably fruit body, preferably in the form of strips) crushed into pieces, 35 ml / v% ethanol solution is added to make 1000 ml. Maintain and brew for about 30 hours. After 30 hours, hot water (or water) is added so that the total amount becomes 1000 ml. It is preferable that the alcohol concentration finally be about 20 v / v% or less.

  The obtained various extracts are filtered or the like as necessary. The extract may be used as an active ingredient as it is. Moreover, it can also concentrate and concentrate as needed, and this can also be made into an active ingredient. Further, by evaporating the water, an extraction component as a solid content can be obtained, and further, a desired dry extraction component can be obtained by drying or the like as necessary. In addition, when using 2 or more types of extraction components as a basidiomycete, it can also extract separately, respectively, and can also extract 2 or more types simultaneously. Furthermore, in consideration of the dosage form and dosage form of the present composition, an additive for stabilizing the formulation or the extraction component can be added when the extract is concentrated or dried. The basidiomycetous raw material water and / or alcohol extract particularly contains many of the active ingredients of the first composition.

(Active ingredient derived from roots of Argiaceae)
The composition of the present invention may contain components extracted from the roots of Argiaceae plants. The Araceae plant is not particularly limited. Various Araceae plants can be used alone or in combination of two or more. A preferred Araceae plant is bamboo ginseng (Panthus ginseng, P. japonicus CA Meyer or Japanese Panaxginseng). In addition, ginseng (Panax ginseng CA Meyer), American ginseng (P. quinquefolium L.), and ginseng (Tanachi ginseng, P. notogingseng) can also be used as medicinal carrots for arginaceae plants. . In order to obtain the components of the composition of the present invention, plant roots selected from Panax ginseng and its related species (hereinafter referred to as roots of Panax ginseng) and plants selected from chixet ginseng and its related species It is preferable to use roots of the roots (hereinafter referred to as roots of chixet carrot, etc.). These carrot roots are usually available in a dry state, including ginseng and chixet carrots and the roots of these closely related plants. Alternatively, it can also be obtained as an alcohol immersion liquid, paste, or extract.

  The roots of the Argiaceae plant may be so-called plant roots, or may be cultured cells. In the case of cultured cells, root-derived cultured cells are preferred. In addition, if the raw material derived from the root of a plant body is included, the raw material containing other parts other than the root of a plant body can also be used.

(Acquisition method of active ingredients from the roots of Araceae plants)
Moreover, when acquiring the active ingredient in this composition, it is preferable to grind | pulverize the root of the carrot of a plant body, and to make it into a powder form and a strip form. More preferably, it is a piece of about 7 mm square or less, more preferably about 4 mm to about 6 mm, and most preferably about 5 mm. A strip shape of 0.5 mm to 2 mm square may be preferable. When using cultured cells as a raw material, it is preferable to use a dry powder.

  When extracting with water, the water to be used is not particularly limited, but it is preferable to heat the extraction. Preferably, it is about 80-about 100 degreeC, More preferably, it is about 90-about 95 degreeC. Further, the amount of water relative to the extraction raw material is not particularly limited, but is about 3 to about 25 parts by weight, preferably about 5 to about 20 parts by weight, more preferably about 20 parts by weight after extraction. The amount of water for extraction is preferably set so that the amount of water is about 200 to about 800 parts by weight (preferably about 500 to 700 parts by weight). This is because when the final extract is prepared in this concentration range, it is a concentration preferable for oral administration as it is, and effective extraction is performed.

  When the heat extraction operation is performed in a state that allows a reduction due to the evaporation of moisture, the initial amount of extraction water is set assuming a reduction in moisture during that time. For example, the extraction is performed by increasing the amount of water by about 50 to 60% with respect to the desired final amount of water. On the other hand, when the heat extraction operation is performed in a state where a reduction due to evaporation of moisture is not allowed, the extraction water amount to be finally obtained may be added to the raw material from the beginning and heated. Preferably, a reflux condenser is used.

  For the heating extraction operation, an open-air container or a reflux condenser can be used. In particular, in order to inhibit the extraction of the active ingredient and maintain the effectiveness of the extracted ingredient, it is preferable to use a material obtained by painting or processing a metal part with a corrosion-resistant coating, in addition to glass, enamel, or ceramic. Although the extraction time is not particularly limited, it is preferably at least 1 hour, more preferably 1.5 hours or more, and further preferably 2.5 hours or more. The upper limit is 3 to 4 hours.

  The following operation can be mentioned as a typical example in the case of extracting the roots of the Argiaceae plant which is a plant body with water. Hot water (800 ml to 1000 ml) is added to about 3 to 20 g of dried carrot roots crushed into small pieces, and decocted so that the remaining amount of the extract is about 200 ml to about 700 ml within the heating range described above. Preferably, the heating temperature is adjusted to about 200 ml to about 700 ml in about 1.5 to 3 hours while maintaining the extract temperature at 90 to 95 ° C. In particular, it is preferable to carry out boiling extraction for about 2 hours using a reflux condenser with about 200 ml to about 700 ml of water for the same amount of carrot raw material. The extract obtained by such an operation becomes a liquid having a concentration suitable for oral administration as it is.

  In the case of extracting with alcohol, it is preferable that the alcohol to be used is a drinkable alcohol in consideration of the case where it may be drunk as it is. That is, it is preferable to use ethanol. When extracting using alcohol, you may extract only with alcohol, However, It is preferable to mix with water and to extract with a liquid mixture. The alcohol concentration is preferably 50 v / v%, more preferably about 35 v / v%. The alcohol-containing extract is not particularly limited, but is preferably heated during extraction. Preferably, it is 50-80 degreeC, More preferably, it is 75 degreeC or less, More preferably, it is 70 degreeC or less. Although the extraction time is not particularly limited, it is preferably 10 hours or longer, more preferably 20 hours or longer, and most preferably about 30 hours or longer. It should be noted that the alcohol concentration is preferably about 20 v / v% at the final oral administration. For example, when extraction is performed with an alcohol solution having a concentration exceeding 20 v / v%, it is preferable to dilute with water after extraction so that the concentration is 20 v / v% or less. Preferably, it is 10 v / v% or less, More preferably, it is 5 v / v% or less. Further, the amount of the extraction liquid with respect to the extraction raw material (carrot root) is not particularly limited, but it is preferably set to 1000 ml of the extraction liquid with respect to about 30 to 200 g of the raw material. It is preferable to use the same container as that used for extraction with water alone. The extraction operation is preferably performed using a reflux condenser.

  The following operation can be mentioned as a typical example in the case of extracting the roots of Araceae plants with a water / alcohol mixture. To about 200 g of dried roots of Araceae plant crushed into small pieces, a 35 v / v% ethanol solution is added to make 1000 ml, and this solution is maintained at about 70 ° C. and decocted for about 30 hours. After 30 hours, hot water (or water) is added so that the total amount becomes 1000 ml. It is preferable that the alcohol concentration finally becomes about 20 v / v%. The extract obtained by such an operation becomes a liquid having a concentration suitable for oral administration as it is.

  The obtained extract is filtered or the like as necessary. The extract may be used as an active ingredient as it is. Moreover, if necessary, it can be concentrated to give a concentrate, which can be used as an active ingredient. Further, by evaporating the water, an extraction component as a solid content can be obtained, and further, a desired dry extraction component can be obtained by drying or the like as necessary. In addition, the root of Araceae plant can use not only one type but two or more types. In that case, an extract may be prepared for each type, or an extract in any combination of two or more types. May be prepared. Furthermore, in consideration of the dosage form and dosage form of the present composition, an additive for stabilizing the formulation or the extraction component can be added when the extract is concentrated or dried. The water and / or alcohol extract of the root family of Araceae contains, in particular, the whole or many of the active ingredients of the second composition, and also contains a part of the active ingredients of the first composition. is doing.

In addition, when using 2 or more types of basidiomycetes as a basidiomycete raw material, an extract can be prepared separately for each type, but can also be extracted simultaneously. The same is true for Argiaceae plants. Furthermore, the basidiomycete raw material and the root raw material of the family Argiaceae can be extracted independently, but the raw material composition containing both can be extracted with the same extraction medium and extracted simultaneously. Preferably, simultaneous extraction is performed. Even in the case of simultaneous extraction, the extraction conditions for the above-mentioned basidiomycete raw materials or root raw materials of Argiaceae plants can be employed. Note that there are two types of basidiomycetous materials and rootstocks of Argiaceae plants: a water extract and a water / alcohol mixed extract, respectively. Therefore, these can be combined in various ways. That is, the following combinations are possible.
Basidiomycetes: Root extracts of Araceae plants Water: Water types Water: Water / alcohol
Water / alcohol: water
Water / alcohol: Water / alcohol

  A typical example of simultaneous extraction is shown below. The fruit body of a specific species of Mannentake crushed into a strip of 7 mm square or less, preferably about 5 mm, the fruiting body of a specific species of Agaricus crushed into a strip, and the root of the Argiaceae plant (preferably Chikusetu) Carrot root), about 6 g each (or 10 g, 5 g, 3 g, or 5 g, 10 g, 3 g) in the order of Mannambo fruit fruit body, Kawaratake fruit fruit body, and Argiaceae root, respectively, add 1000 ml of hot water, Roast so that the remaining amount of the extract is 700 ml within the heating range. For example, the heating adjustment is performed so as to be 700 ml in about 90 minutes. In addition, a raw material mixture having the same form and composition (however, 60 g of fruit body of Amanita bamboo, 60 g of fruit body of Kawaratake, 60 g of root of Araceae plant, or 100 g, 50 g, 30 g, or 50 g, 100 g, 30 g) 35 ml / v% ethanol solution is added to make 1000 ml, and this solution is kept at about 70 ° C. and decocted for about 30 hours. After 30 hours, hot water (or water) is added so that the total amount becomes 1000 ml. It is preferable that the alcohol concentration finally becomes about 20 v / v%. Since these two kinds of extracts each contain the raw material-derived component of the present invention, they can be provided alone as the present composition, but preferably only the water extract or the water extract Is used relatively much. On the other hand, two kinds of extracts can be mixed in advance to make this composition as one composition, or two kinds of products that are mixed at the time of administration, or they are administered separately but simultaneously. Are offered as a set of products.

  The mixing ratio of these two kinds of extracts can be determined as appropriate. For example, a water extract and a water / alcohol extract can be mixed at a volume ratio of about 2: 1 to 4: 1. As described above, in the final administration or eating and drinking stage, if the basidiomycete-derived active ingredient and the root-derived active ingredient are contained, the present composition is composed of only one kind of product. Not only the case but also the composition can be constituted by a combination of two or more products.

  By providing such a composition, the present composition can express various physiological activities. That is, antitumor activity, antihyperlipidemic activity, blood pressure lowering activity, blood glucose level lowering activity and the like can be expressed. At the same time, the patient's QOL can be maintained and improved and health can be improved. Therefore, this composition can be used as a therapeutic or prophylactic agent for tumors, a therapeutic or prophylactic agent for hyperlipidemia, a therapeutic or prophylactic agent for hypertension, and a therapeutic or prophylactic agent for diabetes. It can also be used as a health enhancer or nutritional supplement.

  The antitumor activity expressed by the composition of the present invention has activity particularly against leukemia, lymphoma, cervical cancer, lung cancer, ovarian cancer, breast cancer (metastasis), skin cancer (metastasis), breast cancer, skin cancer. is doing. Examples of leukemia include erythroblastic leukemia. The composition is preferably used as a therapeutic or prophylactic agent for the indication of leukemia or lymphoma.

  The antihyperlipidemic activity expressed by the composition of the present invention has an effect of lowering total cholesterol in blood of mammals including humans. In humans, particularly, it has an action of lowering a relatively large amount of LDL cholesterol relative to HDL cholesterol. It also has the effect of increasing HDL cholesterol. In addition, in humans, it has a triglyceride-lowering effect represented by blood triglyceride concentration.

  In particular, the action of lowering total cholesterol, lowering LDL cholesterol, increasing HDL cholesterol, etc. in humans has a normal blood sugar level (typically a fasting blood sugar level of 120 mg / dl or less) to a border region (for example, fasting blood sugar level). The value is more than 120 mg / dl and less than 140 mg / dl), and the total cholesterol amount is effectively exhibited in patients with normal to hyperlipidemia. For these patients, the blood triglyceride content is also reduced. That is, the composition of the present invention can effectively act on hyperlipidemia as a complication in diabetes, particularly in insulin-independent diabetic patients, and can lower total cholesterol and / or LDL cholesterol. Therefore, the composition of the present invention can be used as a therapeutic agent for hyperlipidemia as a complication in diabetes. The composition of the present invention also has an insulin-like action. That is, when administered to a diabetic patient, a decrease in blood glucose level and blood concentration of C-peptide has been observed. Therefore, the present composition can also be used as a composition for preventing or treating diabetes.

The composition of the present invention can be used in combination with other diabetes therapeutic agents for non-insulin dependent diabetes patients. That is, this composition exhibits a total cholesterol lowering action and an LDL cholesterol lowering action even when used in combination with other agents for treating diabetes. The composition hardly exhibits side effects due to administration of the composition itself, and can reduce side effects caused by other therapeutic agents for diabetes due to an immune activation action or the like.

  In the composition of the present invention, no side effects are observed, or only minor side effects are observed. In other words, side effects commonly observed when antihyperlipidemic agents are administered: numbness of limbs, weakness of limbs, dullness, muscle pain, swelling, decreased urine output, fever, cough, constipation Abdominal pain, chest pain, tiredness, nosebleed, poor complexion, loss of appetite, headache, etc. are not found, conversely, after starting administration, numbness of limbs, feeling body strength, body pain relief, Phenomena such as fatigue, improved complexion, and increased appetite are observed.

  The active ingredient in the present invention is mixed with a pharmaceutically acceptable carrier or additive and used as a composition in a form suitable for administration. The form of the composition is not particularly limited, but liquids, syrups, suspensions, powders, granules, tablets, pills, capsules, emulsions, troches, chewables, suppositories, eye drops, injections, aerosols It can be formulated into elixirs and the like. Moreover, it is also preferable to use a solid (powder) agent that can recover the liquid material by adding water during use.

  Moreover, the composition of this invention can be administered orally or parenterally. Preferably, it is administered orally. The general dosage for oral administration is shown below. The dose is appropriately set according to symptoms, individual physical strength, and the like. As a general dose (ordinary dose), for example, 2 g to 120 g / day / patient (body weight 60 kg as the dry weight of basidiomycetous fruit bodies (preferably ganentake and kawaratake) used as an extraction raw material. .) In particular, in the development of an antitumor effect, the dose can be 12 g to 120 g / day / patient. Moreover, it can be set as 2g-10g / day / patient for expression of effects other than anti-tumor effects, such as a blood glucose level lowering effect, a cholesterol lowering effect, and a neutral fat lowering effect. As a general dose (ordinary dose), for example, 2 g to 60 g / day / patient (body weight 60 kg as the dry root weight of chixetsuninjin etc. (preferably chixetsuninjin) used as an extraction raw material. The same applies hereinafter. ). In particular, in the development of an anti-tumor effect, it can be 6 g to 60 g / day / patient. Moreover, it can be set as 2g-5g / day / patient for expression of effects other than antitumor effects, such as a blood glucose level lowering effect, a cholesterol lowering effect, and a neutral fat lowering effect. More preferably, it is 2.5 g to 3.0 g / day / patient.

  For example, in the combined administration of a typical water extract and an ethanol / water mixture extract, the water extract is 180 to 220 ml (preferably 200 ml) / day / patient and the ethanol / water mixture extract is 45 to 55 ml ( 50 ml) / day / patient, and these are preferably administered twice a day.

  In addition, since the composition of the present invention has extremely low toxicity and does not cause serious side effects, it can be safely administered even at high doses depending on the symptoms. A preferred dosage form for oral administration is a solution or syrup.

  The composition of the present invention has the above-described lowering action such as cholesterol and the lowering action such as blood glucose level, while having little or no side effects. In addition, this composition also has a health promoting effect. Therefore, this composition is not only used as a pharmaceutical composition for preventing or preventing hyperlipidemia and diabetes, but also as a health promoting composition or nutritional supplement. Can be used as a composition. That is, by taking the composition of the present invention by eating and drinking or tube feeding, it is possible to provide a healthy life and improvement of the quality of life. The intake is not particularly limited, but can be lower than the above-mentioned dose for treatment or prevention.

  When the composition of the present invention is used for health promotion or nutritional supplementation, it may be liquid or solid, and can be appropriately formulated into tablets, capsules, chewable agents and the like. Moreover, it is also preferable to use a solid (powder) agent that can recover the liquid material by adding water during use. Furthermore, it may be in a form that can be ingested by tube feeding or via the intestinal tract. Selection of such forms and formulation according to the selection are well-known matters for those skilled in the art.

Example 1
Hereinafter, the present invention will be described with specific examples. However, the present invention is not construed as being limited to these examples.
(Example of preparation of composition)
(Sample 1)
To 1 liter of water, 6 g of dried product of litchi fruiting body, 6 g of dried product of Kawaratake fruit body, and 6 g of dried product of chikutsunin ginseng root were added, capped and extracted by boiling for 90 minutes. The remaining amount of the solution after 90 minutes extraction was approximately 700 ml. Separately, 60 g of dried ganoderma fruit body, 60 g of dried cranberry fruit body, and 60 g of dried ginseng fruit body were added with 35 v / v% ethanol solution to make 1000 ml, and this liquid was maintained at about 70 ° C. For about 30 hours. After 30 hours, hot water was added so that the total amount became 1000 ml. This water / ethanol extract was added to the filtrate of the water extract so that the volume ratio of water extract: water / ethanol extract was 4: 1 and mixed to obtain the composition of Sample 1. .

(Sample 2)
To 1 liter, 5 g of dried litchi fruit bodies, 10 g of dried bamboo shoots, and 3 g of dried roots of chikutsuninjin were added with a lid, and boiled for 90 minutes. The remaining amount of the solution after 90 minutes extraction was approximately 700 ml. Separately, 50 g of dried product of litchi fruiting bodies, 100 g of dried product of Kawaratake fruiting bodies, and 30 g of dried product of chikutsuninjin fruiting body were added to a volume of 1000 ml, and this solution was maintained at about 70 ° C. For about 30 hours. After 30 hours, hot water was added so that the total amount became 1000 ml. This water / ethanol extract was added to the filtrate of the water extract and mixed so that the volume ratio of water extract: water / ethanol extract was 4: 1 to obtain a composition of Sample 2.

(Sample 3)
To 1 liter of water, 10 g of dried ganoderma fruit body, 5 g of dried cranberry fruit body, and 3 g of dried ginseng root were added and boiled for about 120 minutes. The remaining amount was about 170 ml. This solution was used as the composition of Sample 3.

(Sample 4)
To 1 liter of water, 5 g of dried ganoderma fruit bodies, 10 g of dried cranberry fruit bodies, and 3 g of dried chrysanthemum roots were added and boiled for about 120 minutes. The remaining amount was about 170 ml. This solution was used as the composition of Sample 4.

(Sample 5)
To 1 liter of water, 30 g of dried dried carrot root was added, capped, and boiled for about 90 minutes. The volume after extraction was about 700 ml. Separately, a 35 v / v% ethanol solution was added to 30 g of the dried chixet carrot fruit body to make 1000 ml, and this solution was maintained at about 70 ° C. and decocted for about 30 hours. After 30 hours, hot water was added so that the total amount became 1000 ml. The water / ethanol extract was added to the filtrate of the water extract and mixed so that the volume ratio of water extract: water / ethanol extract was 4: 1 to obtain a composition of Sample 5.

(Sample 6)
To 1 liter of water, 30 g of dried dried carrot root was added, capped, and boiled for about 90 minutes. The volume after extraction was about 700 ml. This filtrate was used as the composition of Sample 6. In any sample preparation, the roots of the litchi fruit bodies, the bamboo shoot fruit bodies, and the roots of chikutsuninjin were all crushed into strips of about 0.5 to 2 mm square and used for extraction.

(Measurement of components) The components of the compositions of Samples 1 to 6 were analyzed. The results are shown in Tables 1 and 2. Table 1 shows each component by the content per 100 g of the composition, and Table 2 shows each component by the content per 10 g of the raw material.

  Further, for each 100 ml of sample 5 and sample 6, low molecular components were removed by dialysis and then lyophilized, and this was added to a sample preparation buffer [0.002% bromophenol blue, 2% SDS, 5% In a 50 mmol Tris-HCl buffer (pH 6.5) containing mercaptoethanol and 10% glycerol], it is dissolved to 5%, heated and allowed to cool at 95 ° C. for 5 minutes, and used as an electrophoresis sample. SDS polyacrylamide gel slab electrophoresis was performed on the molecular weight region. Detection was performed by Coomassie brilliant blue staining. As a result, it contained a protein having a molecular weight of 2,4000 Da to 2,9000 Da. As a result, a single band was detected between Trypsinogen (24 kDa), which is a comparative protein, and Carbon Anhydrase (29 kDa).

(Example 2)
(Anti-tumor activity)
Hereinafter, the present invention will be described with specific examples. However, the present invention is not construed as being limited to these examples.
(Preparation of composition) The fruit body of Ganoderma Lucidum, the fruit body of Kawaritake (Coriolous Versicolor), and the root of Chikutsunenjin (P. japonicus CA Meyer) were used as raw materials. Mannentake used was a natural, mature black fruit body collected in a forest in northern China in summer and air-dried at room temperature, avoiding light. Kawaratake was a natural fruit body collected in Japan in the summer and air-dried at room temperature avoiding light. Prickly ginseng used the roots of mature bodies collected in Japan in the summer and air-dried at room temperature avoiding light. 6 g of Mannentake, 6 g of Kawaratake and 6 g of Chikutsunenjin were weighed, and these mixtures were made into small pieces of about 5 mm square. To this mixture, 500 ml of (ion-exchanged water, purity 1 μS / cm or less) was added and boiled for 2 hours while refluxing using a reflux condenser. Then, it filtered and it was set as the composition of the present Example. In addition, per 1 ml of the present composition contains an extract component equivalent to about 0.012 g of garlic bamboo, an extract component equivalent to about 0.012 g of bamboo shoot, and an extract component equivalent to about 0.012 g of chikutsuninjin. This composition was further diluted to 1/4, 1/8, 1/16, 1/32, 1/64, 1/128, 1/256 using the ion-exchanged water.

(Example 3)
A composition of Example 3 was prepared in the same manner as in Example 1 except that 6 g of garlic mushroom, 6 g of Kawaratake, and 6 g of chikutsuninjin were weighed and the mixture was powdered. Moreover, it diluted similarly to Example 2.

Example 4
Confirmation of anti-tumor activity: Growth inhibitory effect of K562 cell line which is human leukocyte cancer cells 150 μl and 20 × 10 ³ culture solutions of K562 cell line were added to the recesses of the microtiter plate. The stock solutions of the compositions of Examples 1 to 3 and 50 μl of the diluted composition were added and cultured at 37 ° C. The cells were cultured for 24 hours, 48 hours, 72 hours, and 96 hours, and cell proliferation was evaluated by the SRB method. The SRB method was performed as follows. 50 μl of 80% TCA (trichloroacetic acid) is added to each recess of the microtiter plate to immobilize the cells for 1 hour. Thereafter, it was washed 4 times and sufficiently dried. 200 μl of 4% SRB (sulfohodamine B) was added to each recess and the cells were stained for 30 minutes, then washed 4 times and dried. 10 mM unbuffered Tris base was added to each recess and stirred for 5 minutes. Then, the light absorbency in wavelength 490nm was measured about each liquid in a recessed part. The ratio of the initial number of cells to the number of cells after culturing for a predetermined time obtained from this result was defined as the growth inhibition rate (%). The result about the composition of each Example of Examples 2-3 is shown to Tables 3-4.

  As shown in Tables 3 and 4, the composition of Example 1 showed a remarkable K562 cell line growth inhibitory effect in the stock solution to 16-fold dilution. Moreover, the composition of Example 2 showed a remarkable K562 growth inhibitory effect in the stock solution to the 8-fold diluted solution. From these, it was shown that these compositions have antitumor activity. It was also shown that anti-tumor activity was high by extracting as strips.

(Example 5)
Clinical administration for tumor patients By the same operation as in Example 1, a stock solution of the composition of the present invention was obtained. This stock solution was administered to 26 patients with various severe tumors, 150 ml at a time, three times a day, continuously for 35 days. As a result, all administered patients were aware of or observed relief of physical pain, increased appetite, improvement of skin condition, reduction of stress, comfortable sleep, improvement of various functional disorders of the body, and the like. In addition, reduction of complications and healing were observed. Table 5 shows examples of lesion degeneration and complete cure, Table 6 shows blood test results, and Table 7 shows immunological test results.

  As shown in Tables 5 to 7, antitumor effects in humans were confirmed by administration of the present composition. That is, favorable treatment results were obtained for cervical cancer, lung cancer, ovarian cancer, breast cancer (metastasis), skin cancer (metastasis), breast cancer, and skin cancer.

(Example 6)
A stock solution of the composition of the present invention was obtained in the same manner as in Example 2 of clinical administration for diabetic patients. At the same time, Chixetsu carrot is made into a strip of about 5 mm square, and 500 parts by weight of 40% ethyl alcohol solution is added to 10 to 20 parts by weight of the strip. The mixture was extracted by heating until the evaporation of the mixture was almost completed to obtain a chikutsujinjin extract. The composition solution and the chixetsu carrot extract were mixed at a ratio of 2: 1, and this solution was mixed with 25 diabetic patients (12 men, 12 ml, 150 ml, twice a day for 25 days). (13 women). As a result, all patients who were treated were aware of or observed relief from physical pain, especially headaches and limb numbness, increased appetite, visual acuity, reduced stress, and comfortable sleep. It was. In addition, reduction of complications and healing were observed. Some patients recovered their sensation in the necrotic leg. Table 8 shows the clinical results.

  As shown in Table 8, hypoglycemia was confirmed in all patients by this clinical administration. According to the present composition, it has been found that there is a significant hypoglycemic effect as well as improvement of subjective symptoms without accompanying side effects.

(Example 7)
(Preparation of composition)
1. 800 ml of hot water is added to 3 g of dried roots of chixet carrot crushed in the form of 0.5-2 mm square pieces of water extraction composition, and the remaining amount of the extract becomes 500 ml in about 30 minutes. Decocted. This extract was directly used as a composition for oral administration.
2. Alcohol / water mixture extract composition Add 0.5% ethanol solution to 30g of dried root of chixet carrot broken into 0.5-2mm square pieces to make 1000ml. Maintained and decocted for about 30 hours. After 30 hours, hot water was added so that the total amount became 1000 ml. The final alcohol concentration was about 20 v / v%. This extract was directly used as a composition for oral administration.

(Example 8)
(Clinical administration example)
The two compositions obtained in Example 7 were used in combination and orally administered to five non-insulin dependent diabetes patients. For administration, these compositions were drunk as they were. The dosage was 200 ml / day for the water extract composition (100 ml each in the morning and evening) and 50 ml / day for the alcohol / water mixed extract composition (25 ml each in the morning and evening). Administration was carried out for 28 consecutive days. These patients were on a diet and no other drugs including a therapeutic agent for diabetes other than the present composition were administered during the administration period. It was not a plant allergy, neuropathy, gastroenteritis, liver dysfunction, or renal dysfunction.

Table 9 shows the results of blood collection for these patients before the start of administration and after the end of the administration period, and the concentrations of blood total cholesterol, LDL cholesterol, and C-peptide were measured.

  As shown in Table 9, blood concentrations of total cholesterol, LDL cholesterol, and C-peptide decreased in all patients. Total cholesterol averaged 75.85% before administration, LDL cholesterol was also 78.78%, and c-peptide was also 84.5%. In addition, it is thought that the blood concentration of C-peptide decreases because this composition exhibits an insulin-like action. In these 5 patients, no symptoms considered as side effects were observed during the administration period. On the other hand, during the administration period, conditions such as relief of body pain, difficulty in fatigue, feeling of body strength, improvement of complexion, and appetite increase were observed.

表１０に示すように、紅参は、総コレステロールおよびＬＤＬコレステロールの低下作用を有していたが、いずれも１０％未満の低下であった。 (Comparative example)
(Clinical administration example)
The blood concentration before and after administration of total cholesterol and LDL cholesterol in an example of administration of red ginseng (a kind of ginseng) powder to diabetic patients was measured. A total of 67 patients were administered. All patients had non-insulin dependent diabetes mellitus, were being treated with diet alone, and no drugs were combined. The dose was 2.7 g / day (divided into 3 times a day before 3 meals), continuous administration for 30 days, and oral administration. The results are shown in Table 10.

As shown in Table 10, red ginseng had a lowering effect on total cholesterol and LDL cholesterol, but both were lower than 10%.

Example 9
(Preparation of composition)
1. For a raw material mixture of 10 g of dried dried fruit bodies of natural garlic mushrooms, 5 g of dried fruit bodies of Kawaratake, and 3 g of dried roots of chiketsu carrot, which were crushed into strips of about 0.5 to 2 mm square, 800 ml of hot water was added and decocted so that the remaining amount of the extract became 500 ml in about 30 minutes. The temperature of the extract during roasting was approximately 90-95 ° C. This extract was directly used as a composition for oral administration.
2. Alcohol / water mixed extract composition A raw material mixture of 100 g of dried fruit bodies of natural garlic mushrooms, 50 g of dried fruit bodies of Kawaratake, and 30 g of dried roots of chiketsu carrot, which were crushed into 0.5 to 2 mm square pieces. A 35 v / v% ethanol solution was added to make 1000 ml, and this solution was kept at about 70 ° C. and decocted for about 30 hours. The temperature of the extract during roasting was approximately 70 ° C. After 30 hours, hot water was added so that the total amount became 1000 ml. The final alcohol concentration was about 20 v / v%. This extract was directly used as a composition for oral administration.

(Example 10)
(Clinical administration example 1)
The two types of compositions obtained in Example 1 were used in combination and were in the diet for one month before the administration, and other drugs including antidiabetic agents were administered during this diet therapy period. Orally administered to 5 patients without. In addition, as shown in Table 1, the patients have normal to borderline blood glucose levels before administration of the present composition, and all are high-risk patients with insulin-independent diabetes. For administration, these compositions were drunk as they were. The dosage was 200 ml / day for the water extraction composition (100 ml each in the morning and evening) and 50 ml / day for the alcohol / water mixture extraction composition (25 ml each in the morning and evening). The administration was carried out for 28 consecutive days, and dietary therapy was continued during this period. In addition, the patients had none of plant allergy, neuropathy, gastroenteritis, liver dysfunction, or renal dysfunction.

  For these patients, blood was collected before the start of administration and after the end of the administration period, and the results of measuring the concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride (TG), glucose, and C-peptide are shown in Table 11. . The total cholesterol, LDL, HDL and triglyceride were measured by the enzyme method, and the c-peptide was measured by the RIA method.

  As shown in Table 11, the total cholesterol and LDL cholesterol showed a tendency to decrease to the same extent or slightly after the end of the administration period. In contrast, HDL cholesterol tended to increase slightly. Triglyceride was reduced in all patients. As for cholesterol, it has been found that total cholesterol and LDL cholesterol tend to decrease, HDL cholesterol tends to increase, and TG also tends to decrease. On the other hand, blood glucose level and C-peptide were almost the same before and after administration. From the above, it was found that this composition can be used for the prevention or treatment of hyperlipidemia. In addition, it was found that patients with normal or boundary blood glucose levels can be used for the prevention or treatment of hyperlipidemia. It was found to be particularly effective for high-risk patients with non-insulin dependent diabetes.

(Example 11)
(Clinical administration example 2)
The two types of compositions obtained in Example 10 were used in combination and continued for 1 month prior to the administration, and other drugs including a therapeutic agent for diabetes were administered during this dietary period. Orally administered to 3 patients. In addition, as shown in Table 2, the patients have high blood glucose levels before administration of the present composition, and all are non-insulin dependent diabetes patients. For administration, these compositions were drunk as they were. The usage and dose were the same as in Example 2. The administration was carried out for 28 consecutive days, and dietary therapy was continued during this period. The patients were none of plant allergy, neuropathy, gastroenteritis, liver dysfunction, or renal dysfunction.

  For these patients, blood was collected before the start of administration and after the end of the administration period in the same manner as in Example 2, and the results of measuring the concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, glucose, and C-peptide were as follows. Table 12 shows.

  As shown in Table 12, total cholesterol was significantly reduced after the administration period (76-99%, average 88%). LDL cholesterol was also significantly reduced (62-94%, average 79%). In contrast, HDL cholesterol increased overall (94-115%, average 106%). As for cholesterol, it was found that, as a whole, total cholesterol and LDL cholesterol significantly decreased and HDL cholesterol tended to increase. On the other hand, the blood glucose level decreased (76 to 91%, average 83%) in all patients, and showed a remarkable blood glucose level lowering effect. About c-peptide, although it decreased remarkably in 2 persons (71%, 78%), 1 person increased (121%), but as a whole, it decreased (86%). That is, high effectiveness was shown also in the blood glucose level lowering action or the c-peptide lowering action. From the above, it was found that this composition can be used for the prevention or treatment of hyperlipidemia. It was also found that the present composition can be used for the prevention or treatment of hyperlipidemia in diabetic patients with high blood sugar levels. At the same time, it was found that it can be used for the prevention or treatment of diabetes.

Example 12
(Clinical administration example 3)
Patients using the two types of compositions obtained in Example 10 in combination for one month prior to the administration and being treated with only the therapeutic agent for diabetes during the diet therapy period Two people were orally administered. In addition, as shown in Table 3, the patients have high blood sugar levels before administration of the present composition, and all of them are non-insulin dependent diabetic patients. Moreover, the diabetes therapeutic agent which the patients were administering was sulfoneureeds, the dosage was 3 mg / day, and it was administered once a day. The usage and dose of this composition were the same as in Example 2. Administration was carried out for 28 consecutive days, and during this period, dietary therapy and administration of antidiabetic agents were continued at the same dosage as before administration. The patients were none of plant allergy, neuropathy, gastroenteritis, liver dysfunction, or renal dysfunction.

  For these patients, blood was collected before the start of administration and after the end of the administration period in the same manner as in Example 2, and the results of measuring the concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, glucose, and C-peptide were as follows. Table 13 shows.

  As shown in Table 13, total cholesterol decreased after the end of the administration period (96%, 89%, average 92%). LDL cholesterol was also significantly reduced (94%, 74%, average 83%). On the other hand, the blood glucose level decreased (86%, 84%, average 85%) in all patients. As for c-peptide, although one person decreased significantly (68%), one increased (107%), but as a whole, decreased (87%). From the above, even when a therapeutic agent for diabetes is used in combination, the present composition significantly exhibits a total cholesterol lowering effect and an LDL cholesterol lowering effect, and is preferably used in combination with a therapeutic agent for diabetes. It was found to be a preventive or therapeutic agent.

(Example 13)
Preparation of Various Composition Stock Solutions and Diluents Hereinafter, the present invention will be described with specific examples, but the present invention is not construed as being limited to these examples.
(Test 1: Antitumor activity)
(Preparation of various composition stock solutions) As raw materials, fruit bodies of Ganoderma Lucidum, fruit bodies of Coriolous Versicolor, and roots of P. japonicus CA Meyer were used. Mannentake used was a natural, mature black fruit body collected in a forest in northern China in summer and air-dried at room temperature, avoiding light. Kawaratake was a natural fruit body collected in Japan in the summer and air-dried at room temperature avoiding light. Prickly ginseng used the roots of mature bodies collected in Japan in the summer and air-dried at room temperature avoiding light.

Three types of composition stock solutions were prepared. Each composition undiluted solution is made from Mannentake, Kawaratake, Chikutsuninjin, but the blending ratio (dry weight ratio) is different.
[Type of composition stock solution and raw material composition]
Composition stock solution RKG1
Mannentake 1.0g, Kawaratake 0.5g, Chikutsutsuninjin 0.3g
Composition stock solution RKG2
Mannentake 0.5g, Kawaratake 1.0g, Chikutsutsuninjin 0.3g
Composition stock solution RKG3
Mannentake 0.6g, Kawaratake 0.6g, Chikutsutsuninjin 0.6g

  In any case, each raw material crushed into small pieces of about 5 mm square was weighed based on each of the above raw material compositions to prepare a mixture of these three types. To this mixture, 50 ml of water was added, and the mixture was boiled for 3 hours while refluxing using a reflux condenser. Then, it filtered and obtained 3 types of composition stock solutions. In addition, per 1 ml of each composition stock solution contains extraction components corresponding to the following raw material weights.

Composition stock solution RKG1
Mannentake 0.02g Kawaratake 0.01g Chikutsutsuninjin 0.006g
Composition stock solution RKG2
Mannentake 0.01g Kawaratake 0.02g Chikutsutsuninjin 0.006g
Composition stock solution RKG3
Mannentake 0.012g Kawaratake 0.012g Chikusetsunjin 0.012g

  Each of these composition stock solutions was further diluted to 1/8 with water to prepare diluted solutions RKG1, RKG2, and RKG3.

(Test Example 2)
Confirmation of antitumor activity A male of B6D2F1 ((C57B1 / 6JxDBA / 2) F1), a first generation hybrid mouse, was obtained from the breeding RAMS “Krjukovo”. On day 0, the mice were inoculated intraperitoneally (ip) with 5 × 10 ⁴ ascites cells of T lymphoma EL-4. To these mice, each stock solution and each diluted solution were orally administered at a rate of 0.1 ml / dose 3 times a day in the following cycles, and RKG1, RKG1 (1: 8), RKG2 , RKG2 (1: 8), RKG3, RKG3 (1: 8) groups (9 or 10 mice) were formed.
1.3 to 7 days 2. 10 to 14 days 3. 17 to 21 days 4. 24 to 28 days 5.31 and 32 days

Furthermore, an untreated group (10 mice) not subjected to any treatment, a CY-100 group (10 mice) to which cyclophosphamide (CY) 100 mg / kg ip was administered on the first day, and cyclophosphamide (CY) CY + RKG1, CY + RKG2, CY + RKG3 groups (10 mice each), and uninoculated (healthy) group (10 mice) in which each stock solution was further administered according to the above cycle to mice administered with 100 mg / kg ip on day 1. Formed respectively. For any group, the observation period was from day 0 to day 90. The rate of weight gain on a specific day, the average survival days and the survival days range, the number of days of life extension (%) relative to the untreated group, and the presence or absence of healing were evaluated. The results are shown in Table 14 and FIGS.

なお、表中、ΔBW₀→₁₃（％）及びΔBW₀→₁₈（％）は、それぞれ、第０日の体重に対する第１３日及び第１８日における体重増加量の割合で表した体重増加率（％）で表したものであり、延命率は、各処置群の平均生存日数から未処置群の平均生存日数をひいた日数を、未処置群の平均生存日数で除したものの割合(％)で表してある。また、表中、ａ，ｂ，ｃ、及びｄはそれぞれ以下の意味を捕捉するものである。
ａ：初期体重と著しい差がある、ｂ：同じ期間における未処置群のマウスの体重と著しい差がある、ｃ：CY-100群のマウスと著しい差がある、ｄ：対応する原液RKG群のマウスの体重と著しい差がある。

In the table, ΔBW ₀ → ₁₃ (%) and ΔBW ₀ → ₁₈ (%) are weight gain rates expressed as the ratio of the weight gain on day 13 and day 18 with respect to the weight on day 0, respectively ( The survival rate is expressed as a percentage of the number of days obtained by subtracting the average survival days of the untreated group from the average survival days of each treatment group minus the average survival days of the untreated group. It is represented. In the table, a, b, c, and d capture the following meanings.
a: Significantly different from initial body weight, b: Significantly different from the weight of untreated mice in the same period, c: Significantly different from mice in CY-100 group, d: Corresponding stock RKG group There is a significant difference with the weight of the mouse.

  (Life extension effect of the composition stock solution and the diluted solution) All three types of composition stock solutions acted to the same extent with respect to the survival rate of mice. That is, the RKG1, RKG2, and RKG3 groups were 4%, 4%, and 4%, respectively. Therefore, it was found that each of these composition stock solutions is not harmful to the degree of identification. Among the RKG1 (1: 8) group, the RKG1 (1: 8) group, the RKG2 (1: 8) group, the RKG3 (1: 8) group, the RKG1 (1: 8) group, and the RKG3 (1: 8) group Seemed to have no substantial effect on the survival rate of mice (life extension rate: -4%, 4%, respectively)). However, in the RKG2 (1: 8) group, the survival rate was 12%, and an effect on the survival rate was recognized.

  FIG. 1 is a graph in which the survival rate of mice in each of the RKG1 (1: 8) group, RKG2 (1: 8) group, and RKG3 (1: 8) group is plotted on the vertical axis and the observation days on the horizontal axis. Indicates. From FIG. 1, only the RKG2 (1: 8) group diluted 8-fold significantly increased the overall survival of mice (ρ = 0.021, Wilkoxon U criteria). In contrast, the RKG1 (1: 8) and RKG3 (1: 8) groups did not appear to have a reliable effect on the overall survival of mice with ascites lymphoma EL-4. It was.

  (Effect of composition on ascites increase) A suitable parameter for assessing the direct anti-leukemic effect in a given model is the measurement of body weight changes up to day 13 and 18 of the experiment. The animal's weight gain during this period is explained by the accumulation of ascites (see Table 1, Figures 2 and 3). The RKG1 stock composition and diluent delayed ascites accumulation by day 13 and the stock solution was better delayed than the diluent. Moreover, in the case of CY co-administration, it exhibited a very good suppressive effect (same as or slightly suppressed from CY-100). Both the RKG2 stock solution composition and the diluted solution delayed the accumulation of ascites, and the diluted solution was better delayed than the stock solution. In the case of co-administration with CY, a good inhibitory effect was exhibited (same as or slightly suppressed as CY-100). The RKG3 stock solution composition and diluent delayed ascites accumulation by day 13 and the stock solution was better delayed than the diluent. Moreover, in the case of co-administration with CY, it exhibited a very good inhibitory effect (same as or slightly suppressed from CY-100).

  From the above, in each of these composition stock solutions, it is most preferably predicted that the antitumor activity of the RKG2 composition dilution solution will be high, followed by the RKG3 stock solution or dilution solution, and then the RKG1 stock solution or dilution solution. It is presumed that. The RKG1 stock solution has already been disclosed in Japanese Patent Application Laid-Open No. 11-292786. The compositions of the present invention, RKG2 and RKG3, were found to have higher antitumor activity than RKG1.

(Example 14)
(Preparation of composition)
1. 800 ml of hot water is added to 3 g of dried roots of chixet carrot crushed in the form of 0.5-2 mm square pieces of water extraction composition, and the remaining amount of the extract becomes 500 ml in about 30 minutes. Decocted. This extract was directly used as a composition for oral administration.
2. Alcohol / water mixture extract composition Add 0.5% ethanol solution to 30g of dried root of chixet carrot broken into 0.5-2mm square pieces to make 1000ml. Maintained and decocted for about 30 hours. After 30 hours, hot water was added so that the total amount became 1000 ml. The final alcohol concentration was about 20 v / v%. This extract was directly used as a composition for oral administration.

(Example 15)
(Clinical administration example)
The two types of compositions obtained in Example 1 were used in combination and orally administered to 9 non-insulin-dependent diabetic high-risk persons to 9 patients. Of the 9 subjects, 3 (G-I) were diabetic patients who were combined with diabetic drugs. In each case, only Sulfonureeds was administered, and patients G, H, and I were administered at 3 mg / day, 3.5 mg / day, and 3 mg / day, respectively. The subjects were allowed to drink each of these extracts as they were. The dosage was 200 ml / day for the water extract composition (100 ml each in the morning and evening) and 50 ml / day for the alcohol / water mixed extract composition (25 ml each in the morning and evening). Administration was carried out for 28 consecutive days. In addition, as for A-F, the other chemical | medical agent containing the therapeutic agent for diabetes other than this composition was not administered at all within the administration period. In addition, all subjects were neither plant allergic, neuropathy, gastroenteritis, liver dysfunction, or renal dysfunction.

  For these subjects, blood was collected before the start of administration and after the end of the administration period, and the results of measuring the concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride (TG), glucose, and C-peptide are shown in Table 15 and Table 16 shows.

  As shown in Table 15, the blood concentrations of total cholesterol, LDL cholesterol, triglyceride, and C-peptide decreased in patients A to F. On the other hand, HDL cholesterol increased and glucose was roughly maintained. Total cholesterol was on average 88.3% before administration, LDL cholesterol was also 78.3%, triglyceride was also 73.2%, and c-peptide was also 77.8%. It was. HDL cholesterol was also 103.5% and glucose was 99.6%. On the other hand, as shown in Table 16, in GH patients, LDL cholesterol and C-peptide tended to decrease, but total cholesterol, HDL cholesterol and triglyceride increased, and glucose was maintained.

  The reason why the blood concentration of the C-peptide of the present composition decreases is considered to be that the present composition exhibits an insulin-like action. In these 9 patients, no symptoms considered to be side effects were observed during the administration period. On the other hand, during the administration period, conditions such as relief of body pain, difficulty in fatigue, feeling of body strength, improvement of complexion, and appetite increase were observed.

  From the above, it was clear that this composition had a cholesterol lowering action. In particular, a subject who does not use a diabetic drug has a preferable cholesterol lowering action in that it can maintain or increase HDL cholesterol while reducing total cholesterol, LDL cholesterol and triglyceride. That is, it has the effect of reducing the LDL / HDL ratio. These effects are preferable effects when administered prophylactically. From these effects, it was clearly understood that the composition was effective for the prevention and treatment of hyperlipidemia.

  In addition, since the present composition expresses C-peptide at the same time as a lowering action, it is particularly effective for prophylactic and therapeutic agents against hyperlipidemia in high-risk individuals and patients with non-insulin-dependent diabetes. I found out that Furthermore, it was found that the present composition can be used for the prevention or treatment of diabetes from its blood glucose level and C-peptide lowering action.

(Example 16)
(Clinical administration example)
The two types of compositions obtained in Example 14 were used in combination and were orally administered to high-risk persons with non-insulin-dependent diabetes mellitus to 6 patients. Six subjects were A to F among the injured persons of Example 2, and after the test of Example 2, only the diet therapy that had been continued before and during the test of Example 2 was performed for 2 months. Immediately after being continuously performed, the test of this example was performed. Among subjects, C and D were administered with a water extraction composition at 200 ml / day (100 ml each in the morning and evening), and A, B, E, and F were 50 ml of an alcohol / water mixture extraction composition. / Day (25 ml each in the morning and evening). Administration continued for 28 days. Note that A to F are not plant allergies, neuropathy, gastroenteritis, liver dysfunction or renal dysfunction at the time of this test. Other than this composition, other therapeutic agents for diabetes are included during the test period. No drug was administered.

  For these subjects, blood was collected before the start of administration and after the end of the administration period, and the results of measuring the concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride (TG), glucose, and C-peptide are shown in Table 17 and Table 18 shows.

  As shown in Table 17, in C and D subjects, all items except HDL cholesterol decreased, but total cholesterol, LDL cholesterol, and triglyceride decreased in Example 15 (subject group not combined with diabetic drugs). It was not reached. On the other hand, in A, B, E, and F, total cholesterol and LDL cholesterol were roughly maintained, but HDL cholesterol was slightly increased. In these 6 patients, no symptom considered to be a side effect was observed during the administration period. On the other hand, during the administration period, conditions such as relief of body pain, difficulty in fatigue, feeling of body strength, improvement of complexion, and appetite increase were observed.

  From the above, the water extraction composition alone has a glucose, C-peptide, and triglyceride lowering action, but the cholesterol lowering action is small, and the water / alcohol extraction composition alone has a cholesterol lowering action and blood sugar level. The C-peptide lowering action was not clear, and HDL cholesterol was slightly decreased, but glucose, C-peptide and triglyceride were increased. That is, it was found that the mixed composition did not have a cholesterol and glyceride lowering action, a glucose etc. lowering action.

  From the above Examples and Comparative Examples, according to the mixed composition, the water extract or the water / alcohol extract composition, respectively, has a lower cholesterol (total cholesterol, especially LDL cholesterol) lowering effect than the effect of single administration. And an antihyperlipidemic composition having a lowering effect on cholesterol and the like than each composition alone. At the same time, it was found that the mixed composition was excellent in C-peptide lowering action and was an antihyperlipidemic composition excellent for high-risk diabetics or diabetic patients.

It is the graph which took the survival rate of the mouse | mouth of each group of the RKG1 (1: 8) group, RKG2 (1: 8) group, and RKG3 (1: 8) group in a test example, and took the observation days on the horizontal axis. . It is a figure which shows the increase in the ascites on the 13th day of each group. It is a figure which shows the increase in the ascites on the 18th day of each group.

Claims (8)

  A physiologically active composition containing one or more amino acids selected from the group consisting of arginine, leucine, valine, alanine, glycine, proline, glutamic acid, serine, threonine, and aspartic acid, and β-glucan object.   The composition of claim 1, wherein the amino acids are arginine, alanine, glutamic acid, and aspartic acid.   Furthermore, the composition of Claim 1 or 2 containing the protein whose molecular weight by SDS polyacrylamide gel slab electrophoresis is 2,4000 Da-2,9000 Da. Furthermore, the composition in any one of Claims 1-3 containing an ergosterol.   Furthermore, the composition in any one of Claims 1-4 containing the 1 type (s) or 2 or more types of metal selected from the group which consists of potassium, magnesium, zinc, and manganese.   A physiologically active composition comprising one or more amino acids selected from the group consisting of arginine, lysine, histidine, phenylalanine, alanine, and glutamine.   Furthermore, the composition of Claim 6 containing the protein whose molecular weight by SDS polyacrylamide gel slab electrophoresis exists in 2,4000 Da-2,9000 Da.   Furthermore, the composition of Claim 6 or 7 containing the 1 type, or 2 or more types of metal selected from the group which consists of potassium, magnesium, zinc, and manganese.

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