JP2002029995A - Pharmacological composition having vasodepressor activity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pharmaceutical composition containing a vasodepressor activity- exhibiting component obtainable from fruit bodies of Mycoleptodonoides aitchisonii, which is safe and less expensive, further stably obtainable all over the year by artificial culturing, and stable in quality, and useful for preventing hypertension attributable to angiotensin I conversion enzyme and the like and/or improving its symptom; and to provide foods and beverages such as functional beverages containing the pharmaceutical composition, and having vasodepressor activity and excellent palatability. SOLUTION: A pharmaceutical composition containing a vasodepressor activity- exhibiting component obtainable from fruit bodies of Mycoleptodonoides aitchisonii, preferably from fruit bodies of Mycoleptodonoides aitchisonii of artificial culture, especially of mushroom bed culture, for example, a pharmaceutical composition containing a hot water-extraction solution or a hot water-extraction product of the fruit body as an active ingredient, and useful for preventing hypertension and/or improving its symptom. Foods and beverages are prepared by using the pharmaceutical composition. Especially, when beverages are prepared, the flock formation and browning during storage can be suppressed by subjecting them to a purification treatment such as a bentonite treatment or an alcohol treatment after a hot water extraction.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a pharmacological composition containing a component exhibiting a blood pressure lowering effect obtained from a fruit body of B. aeruginosa, in particular, an extract or extract having a blood pressure lowering effect obtained from a fruit body of B. aeruginosa as an active ingredient. The present invention relates to a pharmacological composition containing a substance, and a food or drink containing such a pharmacological composition for preventing and / or improving symptoms of hypertension.

[0002]

2. Description of the Related Art Mushrooms (basidiomycetes) have long been known to have various medicinal effects, and as one of such medicinal effects, a blood pressure lowering effect is also known. For example, in Lingzhi fruit bodies, the hot water extract has a blood pressure lowering effect, and the active ingredient is considered to be a polymer compound containing an amino acid having a molecular weight of 100,000 or more. In addition, administration of shiitake or maitake-containing feed has been shown to suppress blood pressure elevation and reduce blood pressure, and although no active ingredient has been pursued, this effect is thought to be the result of affecting lipid metabolism. . Furthermore, it has been reported that in Tsuga sarcophagus, a substance which is considered to be a mixed component of polysaccharide or proteoglycan having a molecular weight of 600,000 or more exhibited a blood pressure lowering action, although the mechanism of action is unknown. Udenone, a tyrosine hydroxylase inhibitory component in Tsutake mushroom, and osponol, a dopamine β-hydroxylase inhibitory component in Pleurotus ostreatus, have hypotensive effects, but their mechanism of action is based on β-receptor stimulation by inhibiting catecholamine biosynthesis. (Taku Mizuno, Masayoshi Kawai, "Mushroom Chemistry and Biochemistry", Japan Society of Press, 49-51, 199
2).

[0003] It has also been reported that extracts of various foods have angiotensin I converting enzyme (ACE) inhibitory activity (Shunro Kawagishi, "Biochemical Experiment 38, Research on Biological Function Regulators in Foods"). Law "Society Press Center, 1
16-119, 1996). ACE cleaves the C-terminal His-Leu of inactive angiotensin I, and has a strong blood pressure increasing action such as vasoconstriction.
On the other hand, is a pressor system enzyme that acts to degrade bradykinin, which has a strong vasodilator action.
It is possible to treat hypertension by inhibiting this ACE. Also, attempts have been made to make functional drinks using extracts or extracts having pharmacological action obtained from mushrooms. For example, JP-B-59-29221 discloses a maitake extract-containing health drink, JP-A-7-25774 discloses a deer mushroom extract-containing drink, and JP-A-8-23938 discloses an agaricus extract beverage. ing. As can be seen from these prior arts, methods for efficiently extracting the active ingredients of mushrooms are variously different depending on the type of raw material mushrooms, the physical properties of the active ingredients, the purpose of extraction, and the like. In particular, when processing into a beverage containing an extract or the like, it is necessary to effectively prevent the occurrence of floc or browning during storage, and the extract of mushrooms has a unique flavor, so it is used. There is also a problem that the palatability is impaired depending on other raw materials, and various efforts have been made to prepare the extract for beverages.

On the other hand, beech agaric (Mycoleptodonoides)
aitchisonii) (local name Kamiharatake) is naturally grown in September-November, overlapping beech trees, fallen oak trees, and dead trees. The umbrella diameter is 3-10 cm, semicircular, white, and later yellowish. It is white, needle-like and, like the surface, later yellowish, the meat is white, soft and water-absorbing, and is known to have a unique aroma.This mushroom has a rich body and is also a very delicious mushroom Are known. And, as an artificial cultivation method of Beech agaric, "Nagano Prefectural Forest Research Report" No. 3, pp. 32-37 (1987).
And “Fukushima Prefectural Forest Research Report” No. 23, 81-101 (1
990), a report on a study on cultivation using raw wood such as beech and cherry blossoms is given in "Food Distribution Technology" Vol. 18, N
o. 1, 17-21 (1989) report a study on log cultivation and cultivation methods using sawdust. According to these reports, although log cultivation can grow to fruiting bodies, many logs can be grown. In addition, there is a problem that it is difficult to cultivate seed pieces with wood chips due to the strong decay power of mycelia, on the other hand, there are many malformations in container cultivation using sawdust, and In bag cultivation, it is difficult to grow fruit bodies, and in any case, it is said that bacterial bed cultivation is impossible with the current technology.

[0005] In addition, although there is a report that a methanol extract of naturally occurring B. agaricus has an anti-inflammatory effect (Esthetic Science. VOL. 40, NO. 5, P368-374, 1999), the fruit body of B. agaricus has been reported. It has not been known that there is a component exhibiting an ACE inhibitory activity and a blood pressure lowering effect, and that an extract or an extract exhibiting an ACE inhibitory activity and a blood pressure lowering effect can be obtained from the fruit body of B. aeruginosa. Furthermore, artificial cultivation,
In particular, it has not been known that a pharmacological composition exhibiting a blood pressure effect can be stably obtained by using a fruit body of a fungus grown on a fungus bed.

[0006]

In Japan, about half of those over the age of 60 are said to be hypertensive or hypertensive reserves, and there is a need for a hypotensive substance as a safe and inexpensive food material. An object of the present invention is to provide a pharmacological composition containing a component exhibiting a blood pressure lowering effect obtained from a fruit body of B. aeruginosa, in particular, a pharmacological composition containing an extract or extract having a blood pressure lowering effect obtained from a fruit body of B. aeruginosa as an active ingredient. Composition, and safe and inexpensive, can be obtained year-round stably by artificial cultivation, and the above-mentioned pharmacological composition obtained from the fruiting body of Bunakaritake with stable quality, and containing these pharmacological compositions It is an object of the present invention to provide a food or drink for preventing and / or improving symptoms of hypertension, for example, a functional drink having a blood pressure lowering effect and excellent palatability.

[0007]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, among the fruit bodies of B. aeruginosa, healthy model animals do not show a hypotensive effect, and It has been found that a component having a strong blood pressure lowering effect is present. In addition, it was confirmed that a beverage capable of suppressing the occurrence of floc, browning and the like can be produced using the above-mentioned extract or extract while maintaining the blood pressure lowering activity. The present invention has been completed based on these findings.

[0008] That is, the present invention provides a pharmacological composition (Claim 1) characterized in that it contains a component exhibiting a blood pressure lowering effect obtained from the fruit body of B. aeruginosa, and exhibits a blood pressure lowering effect obtained from the fruit body of B. aeruginosa. The pharmacological composition according to claim 1, wherein the pharmacological composition containing the component contains an extract or extract having a blood pressure lowering effect obtained from the fruit body of B. aeruginosa as an active ingredient. ) Or the extract or extract is a extract or extract obtained by hot water extraction of the fruiting body, wherein the pharmacological composition according to claim 2 (claim 3) or a fruiting body is used. 3. Use of a dried fruit body.
Or the pharmacological composition according to claim 3 (claim 4) or the extract or extract is an extract or extract subjected to purification treatment after hot water extraction. The pharmacological composition according to claim 5, wherein the refining treatment is a bentonite treatment and / or an alcohol treatment (claim 6),
The pharmacological composition (Claim 7) according to any one of claims 1 to 6, wherein the fruit body of the fungus is a fungus bed cultivation obtained by artificial cultivation. The pharmacological composition (claim 8) according to claim 7, characterized in that the bacterial bed cultivation mixed water with a cultivation nutrient including at least one of a water retention body, dried okara and beer lees. A sterilization step of sterilizing the medium, an inoculation step of inoculating the sterilized medium with a seed of B. aeruginosa, a pre-culturing step of culturing the medium inoculated with the seed of B. aeruginosa, and obtaining a bacterial bed on which the mycelia grew in the medium; A medium culture step of culturing the bacterial bed to obtain a P. agaricus primordium that is not exposed to a physical space capable of growing the fruiting body; Primordium selected from beech Claim cultured under conditions that are exposed to physical space that can be grown in Ritake original Motogako entity, characterized by comprising the culturing step after obtaining Bunaharitake fruit body 8
The pharmacological composition (Claim 9) or the blood pressure lowering effect according to
The pharmaceutical composition (Claim 10) according to any one of claims 1 to 9, wherein at least a part thereof has a blood pressure lowering effect due to angiotensin I converting enzyme inhibitory activity.

Further, the present invention provides a food or drink for preventing and / or improving symptoms of hypertension, which comprises the pharmacological composition according to any one of claims 1 to 10 (claim 11).
And, the food and beverage, tea-based beverages, nutritional drinks, fruit and vegetable-based beverages, carbonated beverages, low-calorie beverages, beverages selected from alcoholic beverages, prevention and prevention of hypertension according to claim 11, wherein And / or a food or beverage for improving symptoms (claim 12).

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The fruit body of B. aeruginosa used in the present invention may be either a natural fruit body naturally growing in nature or an artificially cultivated fruit body. Pruned beetles are preferred. In the case of natural beech agaric fruiting bodies that grow naturally in the natural world, the component content etc. fluctuates depending on the habitat and climate, and the harvest cannot be performed stably throughout the year. It can be harvested stably throughout the year without being affected by weather and climate. Further, the artificial cultivation method is not particularly limited, but fungal bed cultivation, which can inexpensively and stably harvest beech agaric with stable quality such as component content, is more preferable than log cultivation. Here, the fungal bed cultivation refers to a method of inoculating a seed material into a material composed of a water retention body and a nutrient source without using a log, and cultivating the material in an environment in which temperature, humidity, illuminance and the like are controlled.

In a preferred embodiment of such fungal bed cultivation,
A water retaining body, a culture source for cultivation containing a nutrient source including at least one of dried okara and beer lees, and a sterilization step of sterilizing a medium mixed with water, and inoculating the sterilized medium with a seed of B. agaricus Inoculation step, culturing the medium inoculated with the seed fungus of B. aeruginosa, and pre-culturing step to obtain a bacterial bed in which mycelia grew in the medium, and exposing the bacterial bed to a physical space capable of growing into fruiting bodies A medium culturing step to obtain an undisturbed P. agaricus primordium, and a primordia selected from among the P. aeruginosa primordia not exposed to a physical space capable of growing the fruiting body, the B. agaricus primordium can grow into a fruiting body A specific example of artificial cultivation comprising a post-culturing step of culturing under conditions exposed to a physical space to obtain a fruit body of B. aeruginosa is obtained. Here, the physical space that can grow into a fruiting body is
It means a space in which fruiting bodies grow outward from the culture medium. For example, when the culture medium is sealed with a plastic bag or the like, it means the space outside the sealed container.

[0012] As the Bunaharitake strains used in the present invention, any strains including the strain resulting hypotensive effect from commercially available strains and nature as long as a strain belonging to Bunaharitake containing the ingredients shown from the fruiting bodies of the Bunaharitake However, it is particularly preferable to use B. aeruginosa BNH-3, which is excellent in hyphal growth and primordium formation. The Buna-haritake BNH-3 strain was purely isolated by the present inventor from a fruiting body that had grown naturally on a dead tree in the mountains of Minami-Akita-gun, Akita Prefecture. The culture on a potato dextrose agar slant medium was about 4 ° C. It can be stored at a temperature, and it is desirable that the stored strain be inherited in about 3 to 6 months. The morphological characteristics of the fruiting bodies, hyphae and spores of this strain are as follows. Fruiting bodies are clusters, umbrellas are fan-shaped to spatula-shaped, 3-8 x 3-10 cm. The surface is hairless and smooth, white to slightly yellowish. The meat is white, 2-5 mm thick. The edges are thin and slightly tooth-like. The hypha composition is a thick-film hypha with a width of 4 to 10 μm,
Two hyphae of 3.5 to 5 µm width, thin mycelia with swelling and twist. Spores are intestinal, colorless, 2-2.5 x 5-
6.5 μm.

[0013] Based on the above morphological characteristics, the bacterium was identified by Rikuya Imazeki and Tsuguo Hongo, "Primary Color Japanese New Fungi Illustration Book II" (published first edition on May 31, 1989 by Hoikusha). It is clear that it belongs to Under the Budapest Treaty on the International Recognition of the Deposit of Microorganisms in Patent Procedures, the bacterium was found on April 7, 1999, at 1-3-1 Higashi, Tsukuba City, Ibaraki Prefecture, Japan. Deposited at the Engineering Research Institute as FERM BP-6697.

In the fungus bed cultivation of the fungus bed of Beech agaric, water-retaining bodies used in the culture medium include sawdust derived from conifers such as cedar, hinoki and pine, sawdust derived from broadleaf trees such as beech, oak and oak, and mushroom cultivation in recent years. In addition to corn cob (corn-shaft crushed product) used as a sawdust substitute, commercially available bacterial bed materials and the like can be exemplified, and these materials may be used alone or 2
A mixture of two or more species can be used.

[0015] In addition, in the fungus bed cultivation of Beech agaric,
As a nutrient for cultivation used in the medium, an essential nutrient of either beer lees or dried okara and a nutrient other than the selected essential nutrient are used in combination. Examples of other nutrient sources include rice bran, general bran, dedicated bran, corn bran, and the like, which are usually used for cultivation of mushrooms. When a nutrient for cultivation that does not contain both beer meal and dried okara is used in the culture medium, not only the growth of mycelia is slow, but also it becomes difficult to obtain fruit bodies excellent in size and shape.

The mixing ratio of the water retaining body and the nutrient for cultivation is preferably in the range of 10: 0.7 to 10: 4 in terms of fresh weight ratio, and particularly preferably in the range of 10: 2 to 3. The water content may be adjusted to 60 to 70% per final medium,
More preferably, it is about 65%. Furthermore, soybean hulls, dried yeast, pH adjusters, etc., which are usually used in mushroom cultivation, can also be added as medium components.

As described above, the fungal bed cultivation of B. agarita consists of a pre-culture step, a middle-culture step, and a post-culture step, in which the mycelia of B. agaricus are sufficiently grown in a medium under specific culture conditions to form fruiting bodies. A culturing step for obtaining a bacterial bed for the cultivation, a medium culturing step for culturing the bacterial bed under the specific culturing conditions to form a primordial bamboo shoot, And a post-culturing step of growing the fruit body to a fruit body, whereby a fruit body of B. agaricus having a stable quality such as the content component can be obtained.

In the pre-culturing step, a medium containing a water retaining body, a nutrient for cultivation and water is sterilized by pressure, and then a fungus of Bunaku mushroom is inoculated, and the temperature is 15 to 35 ° C, preferably 21 to 27 ° C.
This is a step of culturing under a dark condition at a humidity of 40 to 80%, preferably about 60 to 70%, spreading mycelia in the medium, and accumulating nutrients for generating fruit bodies in the mycelium. The number of days of culture ripening, that is, the number of days required for mycelia to spread throughout the medium and the number of days required for accumulating nutrients in the mycelium are preferably 25 to 90 days when a 1.2 kg bag is used, and usually 25 to 90 days. The fruiting body does not occur in less than days, or it takes a considerable number of days in the subsequent middle culture step. At this time, it goes without saying that the number of days required for the preculture step varies depending on the size of the culture vessel used and the amount of the inoculum inoculated.

The medium culturing step is, as described above, a step for forming a fungus bed after completion of the pre-culturing step, to form a fungus bed.
22 ° C, preferably 12-16 ° C, humidity 80-100
%, Preferably 85 to 95%, illuminance of 50 lux or more,
When culturing is preferably continued at 50 to 500 lux for 25 to 60 days, for example, a P. aeruginosa primordium that is not exposed to a physical space that can grow into fruiting bodies, such as between a bacterial bed and an inner surface of a container, is formed.

The post-culturing step is a step for growing, as described above, a P. aeruginosa primordium that has not been exposed to a physical space capable of growing into a fruit body after the completion of the medium culture step, into a fruit body. A beech agaric primordium that is not exposed to a physical space capable of growing on the fruiting body obtained in the culturing step is formed.
22 ° C, preferably 12-16 ° C, humidity 80-100
%, Preferably 85 to 95%, illuminance of 50 lux or more,
If cultivation is continued for 5 to 20 days, preferably at 50 to 500 lux, and under the condition of being exposed to a physical space in which the fungus can grow into a fruit body, the fungus can grow into a fruit body.

For the cultivation of Bunakaritake, a cultivation container is usually used because of the simplicity of sterilization of the culture medium, and the cultivation container includes a cultivation bag and the like. As shown in FIG.
It is preferable that the container is made of a transparent or translucent material so that the formed beech agaric primordium 2 can be visually observed from the outside of the container. In addition, a single B. agaricus primordium having a diameter of about 3 cm selected from a B. agaricus primordium, which is formed between the fungal bed 3 and the inner surface of the cultivation container 1 and is not exposed to a physical space capable of growing fruit bodies. It is preferable to culture 2a in order to obtain a fruiting body 4 larger than naturally occurring beech mushroom. Further, the cultivation container 1 having a rectangular cross section or the like is laid on its side, and the peripheral portion 5 of the cultivation container in which the bunari mushroom primordium is formed is cut off so that the bunari mushroom primordium 2a faces upward. It is preferable to harvest the large fruiting body 4 of uniform shape by cultivating the fungus primordia 2a under the condition of being exposed to a physical space in which the body can grow.

The pharmacological composition of the present invention may be any composition containing a component exhibiting a blood pressure lowering effect obtained from the fruit body of B. aeruginosa.
In addition to the extract or extract exhibiting a blood pressure lowering effect obtained from the fruit body of B. agaricus, or a composition containing such an extract or extract as an active ingredient, the body of B. agaricus as such or air-dried, hot-air dried or freeze-dried, and then pulverized. Pulverized products and granulated, encapsulated, and tableted products of the pulverized products by a conventional method can be used.

The extract or extract having a blood pressure lowering effect according to the present invention can be obtained by extracting the fruit body of B. agaricus with normal temperature water, hot water, an alcohol-containing aqueous solvent, etc., preferably hot water extraction. The fruiting body may be extracted as it is or may be dried to be preserved, but dried matter is preferred in terms of extraction efficiency, ease of handling, and the like. The fruiting body may be extracted as it is, or may be extracted by pulverizing in advance. The temperature at the time of extraction is 2
The range of 0 to 135 ° C. is preferred, and the extraction time is 5 to 240 ° C.
Minutes are preferred. Then, after an extraction treatment such as hot water extraction, the extract obtained by removing the insoluble residue can be concentrated and dried to obtain a Bunakaritake extract, but when producing a beverage, the insoluble residue is removed. Thereafter, it is preferable to perform a purification treatment. The concentration of the extract is not particularly limited as long as it is a known concentration method. Can be exemplified. Regarding drying after concentration, any method may be used as long as it is a known method, and specific examples thereof include an air drying method, a heat drying method, a spray drying method, and a freeze drying method.

The pharmacological composition of the present invention has a blood pressure lowering effect at least in part due to a strong ACE inhibitory activity, and exhibits a blood pressure lowering effect by oral administration to SHR (spontaneously hypertensive rat). Since oral administration to healthy rats did not show a blood pressure lowering effect, it can be expected that the effect will be exerted only to those with a predisposition to hypertension. Therefore, the pharmacological composition of the present invention can be used as an agent for preventing and / or improving symptoms of hypertension and as an active ingredient of a food or drink for preventing and / or improving symptoms of hypertension. And the pharmacological composition containing the component having a blood pressure lowering effect of the present invention,
Usually, the intake of 100 mg to 20 g / kg body weight / day in terms of dry fruit body produces a blood pressure lowering effect, but the intake can be appropriately adjusted according to the symptoms, sex, age and the like. When used as an agent for preventing and / or improving symptoms of hypertension, for example, it can be used as an orally administered drug by mixing with, for example, excipients generally used in pharmaceutical applications.

The food or drink for prevention and / or symptom improvement of hypertension of the present invention, which comprises the above-mentioned pharmacological composition of the present invention, comprises the pharmacological composition as a part of the raw material of the food or drink. It can be obtained by using, or by adding or blending in the manufacturing process or after the manufacturing. Such foods and drinks include, for example, yogurt, drink yogurt,
Juices, milk, soy milk, alcoholic beverages, coffee, tea, sencha, oolong tea, sports drinks and other drinks, cookies, bread, cakes, baked sweets such as crackers, Japanese sweets such as yokan, pudding, jelly, Frozen desserts such as ice creams, sweets such as chewing gum and candy, snacks such as crackers and chips, noodles such as udon and buckwheat, fish paste products such as kamaboko, ham, fish sausage, miso, soy sauce, dressing ,
Seasonings such as mayonnaise and sweeteners, tofu, konjac,
In addition, various side dishes such as tsukudani, gyoza, croquettes, salads, soups, stews and the like can be specifically exemplified.

Hereinafter, various beverages containing the pharmacological composition of the present invention will be described more specifically. A pharmacological composition suitable for a beverage from the fruit body of B. agaricus is extracted by extracting the body of B. agaricus with hot water at 60 ° C. or more, preferably at 90 ° C. or more for 30 minutes or more, preferably about 60 minutes. It can be obtained as a liquid. The hot water extraction can be performed at a temperature of 100 ° C. or more under pressure, but can also be performed at around 100 ° C. under normal pressure.
The amount of the extract at the time of extraction is not particularly limited, but it is preferable to use 10 to 20 times the amount of hot water with respect to the weight of the dried mushroom in terms of cost, extraction efficiency, and the like.
A solvent such as ethanol can be appropriately added as an extract, but it is preferable to extract only with water from the viewpoint of cost and ease of handling at a manufacturing site. In addition, enzymes such as cellulases and peptidases can be used to improve the recovery rate during extraction.

The fruiting body may be extracted as it is, but it is preferable to extract the fruiting body from dried and storable fruiting body in order to obtain an extract having excellent quality. The drying method is not particularly limited as long as it is a known drying method such as a hot air drying method and a freeze drying method, but a drying method using a hot air dryer is economically excellent. The drying temperature in such a hot air drying method is preferably about 60 to 70 ° C., and by drying in this temperature range, generation of a burning smell and a decrease in blood pressure lowering activity due to the action of an enzyme contained in fresh mushrooms are suppressed. be able to. After drying, the fruiting bodies are preferably crushed and then extracted, since the extraction rate is improved. After extracting the mushrooms or the pulverized mushrooms with or without stirring, centrifugation, solid-liquid separation is performed singly or in combination with solid-liquid separation operations such as filtration, and then concentrated using the above-described concentration method as necessary. By doing so, an extract can be prepared. Further, the extraction operation can be performed a plurality of times to improve the extraction efficiency.

Although the obtained extract can be added to the beverage as it is, it is particularly preferable to carry out a purification treatment for effectively suppressing the occurrence of floc and browning during storage. Such a purification treatment is not particularly limited as long as it is a post-extraction treatment that can maintain the quality of the container-containing beverage such as floc during storage, generation of browning and the like,
Specific examples of the treatment include bentonite treatment, alcohol treatment, and activated carbon treatment. Bentonite treatment, alcohol treatment, and the like, which do not cause a decrease in the blood pressure lowering effect of B. agaricus, are preferred.

The above-mentioned bentonite treatment is carried out at about 0.1 to 5% by weight, preferably 1% by weight, based on the extract.
After adding about bentonite and stirring for about 10 minutes, the mixture is allowed to stand for 1 to several hours, and then sterilized after removing insoluble components by solid-liquid separation means such as filtration and centrifugation. At the time of solid-liquid separation, about 1 to 5% by weight of celite or the like can be used as a filter aid. Examples of the sterilization method include, for example, heat sterilization at 95 ° C. for about 60 minutes, or filtration sterilization using a membrane filter having a pore diameter of 0.45 μm that can prevent the transmission of contaminating microorganisms.

In the alcohol treatment, for example, about 25 to 200% by volume of ethanol is added to the extract, and the mixture is stirred and allowed to stand at room temperature for 1 hour or more to remove a polymer compound having low solubility in ethanol. Precipitating and precipitating the insoluble component, and then performing a solid-liquid separation treatment such as celite filtration in the same manner as the bentonite treatment, followed by concentration under reduced pressure to remove ethanol, followed by centrifugation and sterilization. .

The activated carbon treatment is not particularly limited as long as it is a treatment for sterilizing an activated carbon treatment liquid obtained by a known activated carbon treatment. Granular or powdery activated carbon may be used in the activated carbon treatment. Activated carbon processed into a plate shape can also be used. When filtering using activated carbon processed into a plate shape, there is no need for a subsequent solid-liquid separation operation.

Further, these purification treatments may be carried out by appropriately combining the above-mentioned bentonite treatment, alcohol treatment, activated carbon treatment and the like. For example, bentonite and activated carbon may be added to an extract to which ethanol has been added. Alternatively, ethanol may be added to the extract to which bentonite or activated carbon has been added. The extract obtained after the purification treatment thus obtained can be concentrated and used, but it is preferable to use it as a beverage raw material at the same concentration in terms of cost. At that time, ethanol can be added from the viewpoint of preservation and the like.

The amount of the extract used in preparing various beverages using the extract obtained by the above method as a raw material can be appropriately determined so as to give an excellent flavor. Because you expect
It is preferable to set so as to contain about 0.1 g to 2 g of an extract from Buna mushroom per dry weight of the beverage in the container. In the preparation of various beverages, any sugars, flavors, food additives and the like used in the normal formulation design of various beverages can be used. In addition, Panax ginseng extract, Eleuthero extract, Eucalyptus extract, Tochu tea It may be used in combination with other functional materials such as extracts. In addition, as for the production method of various beverages, an existing reference book, for example, “Revised new edition, soft drinks” (Korin Co., Ltd.) can be referred to, and representative beverages will be described below.

(Tea-based drink) The beech agaric extract is easy to match with any tea such as green tea, semi-fermented tea (oolong tea), and fermented tea (black tea). Among them, Chinese tea, especially golden katsura and jasmine tea When tea leaves are used, the mushroom-specific flavor is masked. In addition, the above tea leaves may be used alone, and also, Tochu tea, persimmon leaves, Kumasa tea,
It may be used in combination with tea leaves that can be expected to promote health, such as Gabalon tea, corn tea, hub tea, and chrysanthemum tea. The method for producing the tea leaf extract is not particularly limited, but it is desirable to use 0.6% by weight or more of tea leaves to mask the mushroom-specific flavor. And the extraction step of mushrooms and the extraction step of tea leaves are preferably separate steps from the viewpoint of efficient extraction of the blood pressure lowering active ingredient,
For example, it is preferable to add and mix a separately prepared beech agaric extract to the tea leaf extract.

(Energy drink) An energy drink can be produced by adding and blending a Buna agaric extract extract with or before or after a component usually used for the manufacture of an energy drink. The mushroom flavor is masked by the body feeling of sugar and the characteristic flavor of vitamin mix and healthy drink flavor.

(Fruit / vegetable drinks) Fruit / vegetable drinks are selected from fruit juices such as oranges, apples, grapes, peaches, strawberries, bananas and lemons, and vegetable juices such as tomatoes, carrots, cabbage and celery. One or two or more types can be produced by adding and blending a Buna agaricus extract, and such a fruit / vegetable beverage containing a Buna agarica extract has a mushroom flavor that matches well with fruit juice or vegetable juice. And very easy to drink.

(Carbonated beverage) A carbonated beverage can be produced by adding and blending a beech agaric extract with or before or after a component usually used for the production of a carbonated beverage. Carbon dioxide pressure of the same level (0.1 ~
0.4 Mpa). A carbonated beverage generally has a feature that the aftertaste is sharp, and the mushroom flavor can be masked by converting the flavor of the mushrooms having a feeling that the aftertaste remains to a carbonated beverage.

(Low-calorie beverages) High-sugar-concentration beverages have the image of causing obesity. To eliminate this image, high-sweetness sweeteners such as stevia, aspartame, and sucralose, and erythritol and maltitol are used. A low-calorie beverage is prepared by using a low-calorie sweetener such as a sugar alcohol. Addition and blending of the Buna mushroom extract can be performed in any step, and the mushroom odor can be masked by selecting a flavor. Preferable examples of such flavor include plum flavor and litchi flavor.

(Alcoholic Beverage) An alcoholic beverage can be produced by adding and blending Buna-harita mushroom or a Buna-harita mushroom extract to any step of the production of alcoholic beverages such as low-malt beer, whiskey and liqueurs. After brewing such alcoholic beverages such as low-malt beer and whiskey and liqueurs, it is preferable to produce the mixture by adding and blending an extract of Bunakaritake. Such an alcoholic beverage containing a Beech agaricus extract has a mushroom flavor and is easy to drink.

[0040]

EXAMPLES The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples. Example 1 [Bacterial bed cultivation of Bunagaritake] A total of 100 obtained by mixing 380 g of beech sawdust, 37.5 g of dried beer lees, 37.5 g of dried okara, and 545 g of tap water.
0 g was packed in a PP (polypropylene) bag for 1.2 kg to prepare a medium. Further, the bag was covered with a polypropylene cap sandwiched with a filter, sterilized under pressure at 121 ° C. for 50 minutes, and after cooling the sterilized medium, inoculated with a fungus of Bunakari mushroom, at a temperature of 23 to 25 ° C. in a dark place. Humidity 60
Preculture was performed for 40 days under the conditions of 〜80%, and then the process was shifted to a medium culture step. In the medium culturing step, the temperature is 13 to 15 ° C., the humidity is 80 to 95%, and the illuminance is 200 lux.
After culturing for a day, the primordial fungus was formed. One portion of the bag portion where the primordium having a diameter of about 3 cm was recognized in the bag was cut out, and then the process was shifted to a post-culture step. In the post-culture step, the temperature is 13 to 15 ° C., the humidity is 80 to 95%, and the illuminance is 20.
After culturing for 17 days under the condition of 0 lux, the strain grew into one strain of B. agaricus. The obtained beech agaric fruit body was 232.5 g, and the total number of days required for cultivation was 87 days.

Example 2 [Preparation of extract from fruit body of B. aeruginosa] 60 g of freeze-dried and crushed fruit body of B. aeruginosa was placed in a glass container, 1.5 L of distilled water was added, and heat extraction was performed at 100 ° C. for 60 minutes. Then, by removing the Bunakaritake residue, a brown Bunakaritake extract was obtained. The extract was freeze-dried to obtain 17.4 g of a brown extract. One example of the physicochemical properties of the extract is shown below. (A) Color and form: brown powder (b) Chemical composition: crude protein 40-45%, crude fat 0.1%
Hereinafter, crude fiber 0.1-0.2%, crude ash content 10-15%,
Soluble nitrogen-free 30-40% (c) Solubility: water soluble

Example 3 [ACE inhibitory activity of the extract] 50 mg of the Prunus agaricus extract of Example 2 was dissolved in 1 ml of distilled water, and the ACE inhibitory activity was measured. Distilled water was used as a control. The ACE inhibitory activity is determined by the method described in the literature (Shunro Kawagishi, "Biochemical Experiment Method 38, Research Methods for Biological Function Modulating Substances in Foods", Gakkai Shuppan Center, pages 119 to 121, 199
It was measured by the method described in 6). Table 1 shows the results. For comparison, various edible and medicinal mushrooms were treated in the same manner as in Example 2, and the ACE inhibitory activities of the obtained various extracts were measured in the same manner as described above. These results are also shown in Table 1. As can be seen from Table 1, beech agaric extract (5
(0 mg / ml) was 76.0%, showing the highest inhibitory activity among the mushrooms used as a comparison.

[0043]

[Table 1]

Example 4 [Hypertension lowering activity by SHR] 500 mg / kg of the Prunus agaricus extract of Example 2 was added to SH
R (spontaneously hypertensive rat) was orally administered, and the blood pressure lowering activity was measured. Distilled water was used as a control. Then, an experiment was conducted with 8 animals per group in each of the test group and the control group, and the blood pressure lowering activity was measured as follows. A 12-week-old SHR male was purchased from Charles River, and preliminarily reared for 1 week. After that, a sample or control at each concentration was orally administered intragastrically using a sonde. Non-invasive blood pressure measuring device (Softlon B
P-98). Table 2 shows the results. No change in blood pressure was observed in the control group, but 2 hours after administration in the test group.
Blood pressure began to decrease from time to time, and showed a maximum blood pressure lowering activity (a change in blood pressure of −22.4 mmHg) after 6 hours. In addition, blood pressure lowering activity was observed even after 24 hours.
Eight hours later, he returned to his original blood pressure.

[0045]

[Table 2]

Example 5 [Hypertensive activity in healthy rats] 500 mg / kg of the P. aeruginosa extract of Example 2 was added to Wi
Star rats were orally administered and the blood pressure lowering activity was measured. Distilled water was used as a control. The test area,
The control group was performed with 5 mice per group.
Blood pressure lowering activity was measured in the same manner as in Example 4 except that ar rats were used. Table 3 shows the results. No change in blood pressure was observed in both the test group and the control group. From this, it was confirmed that the administration of the Buna mushroom extract did not affect the blood pressure of healthy rats.

[0047]

[Table 3]

Example 6 [Production of a Beverage Agaricus Extract-Containing Beverage] (Examination of Extraction Temperature) The fruit body of B. agaricus obtained in Example 1 was dried at 65 ° C. using a hot-air dryer, and then pulverized with a mill. . Using 2 g of this dried and crushed beech pot,
40m of hot water with the temperature changed to 80 ℃, 100 ℃, 120 ℃
After extracting for 40 minutes in 1 l, the resulting extract was lyophilized and weighed, and the ACE inhibitory activity of each dried extract 30 mg / ml solution was measured in the same manner as in Example 3. Table 4 shows the results. Table 4 shows that it is preferable to extract at around 100 ° C.

[0049]

[Table 4]

(Examination of Extraction Time) The fruit body of Prunus agaricus obtained in Example 1 was dried at 65 ° C. using a hot air drier, and then pulverized by a mill. This dried pulverized beech agaric 2
g in 20 ml of hot water at 100 ° C.
Minutes, 40 minutes, 60 minutes after extraction, filtered through filter paper,
After the obtained extract was freeze-dried and weighed, the ACE inhibitory activity of each dried extract 30 mg / ml solution was measured in the same manner as in Example 3. Table 5 shows the results. From Table 5,
It can be seen that it is desirable to extract for 60 minutes or more.

[0051]

[Table 5]

(Purification Treatment of Extract) After extracting 300 g of the crushed dried beech mushroom in 4500 ml of boiling water for 60 minutes, the mixture was filtered with filter paper. The extraction residue is further extracted in 3000 ml of boiling water, filtered through filter paper,
The first filtrate and the second filtrate were combined to obtain an extract.
The extract was concentrated under reduced pressure until the liquid volume reached 300 ml to obtain a crude extract. 50 ml of the crude extract was heat-sterilized at 95 ± 5 ° C. for 60 minutes to obtain an extract.

After 50 ml of the crude extract was centrifuged (3000 rpm, 5 min.), 95 ± 5
The extract was sterilized at 60 ° C. for 60 minutes to obtain an extract, and 50 ml of the crude extract was filtered through plate-like activated carbon.
Sterilize under the condition of 0 minutes to make an extract.
0.5 g of bentonite was added to the mixture, and the mixture was stirred for 10 minutes and allowed to stand for 1 hour. Then, filtration was performed under reduced pressure using filter paper (Toyo Filter Paper No. 2) packed with celite to a depth of about 5 mm. , And then centrifugation (3000 rpm)
m, 5 min. ) And sterilized at 95 ± 5 ° C for 60 minutes to obtain an extract. 50 ml of the crude extract was added with 50 ml of ethanol, stirred, and allowed to stand at room temperature for 1 hour. The solution was filtered under reduced pressure using filter paper (Toyo Filter Paper No. 2) spread to about 5 mm, concentrated under reduced pressure to 50 ml, centrifuged (3000 rpm, 5 min.), And subjected to 95 ± 5 ° C.
The extract was sterilized under the conditions for 60 minutes to obtain an extract, and treated exactly in the same manner except that the amount of ethanol to be added was 100 ml.

(Evaluation of Purification Treatment)
The ACE inhibitory activity, the amount of floc (origin) generated, the degree of coloring, the flavor, and the solid content were evaluated for each item. The ACE inhibitory activity was determined by diluting each extract 20-fold, and then measuring the inhibitory activity by the method described above. The amount of floc (origin) generated was determined by dissolving 2 ml of each extract in 180 ml of deionized water to prepare a neutral (non-adjusted) test solution and an acidic (adjusted to pH 3 with citric acid) test solution, and allowed to stand at room temperature for one week. The amount of floc generated after placing was measured visually, and the floc when the extract was acidic was evaluated as 3, and the floc not observed at all was evaluated as 0. After the neutral (unadjusted) test solution was allowed to stand at room temperature for one week,
The absorbance at 420 nm was measured. The flavor was comprehensively evaluated relative to the neutral (non-adjusted) test solution, and scored and evaluated on a five-point scale, with five points having good flavor and one point having bad flavor. The solid content was determined by measuring the weight of the solid content in 1 ml of the extract. Table 6 shows the results. Table 6
Therefore, it can be determined that the extracts are particularly excellent.

[0055]

[Table 6]

(Prescription of tea-based beverage) Using the extract of jasmine tea, golden katsura, black tea and green tea extracted with hot water, adjusted with deionized water so that the percentage of tea leaves used is 0.8% by weight. did. After adding the above-mentioned extract equivalent to 0.23% by weight, filling in a bottle and sterilizing according to a conventional method,
Samples 1 to 4 were used, respectively.

(Formulation of Energy Drink) A beverage prepared according to the following formulation was filled in a bottle, and then sterilized according to a conventional method to prepare Sample 5. Extract equivalent 4.0 g Fructose dextrose liquid sugar 117 g Galacto-oligosaccharide 2.0 g Citric acid 3.0 g Vitamin mix 2.6 g Nutritional drink flavor 2.0 g Deionized water Add 1 kg in total.

(Prescription of fruit juice beverage) A beverage prepared according to the following formulation was filled in a bottle, sterilized according to a conventional method, and a sample 6 was prepared.
And Extract equivalent 2.3 g Cloudy apple juice 900 g Apple flavor 1.0 g Deionized water Add to a total of 1 kg.

(Prescription of Mixed Vegetable Beverage) A beverage prepared according to the following formulation was filled in a bottle, and then sterilized according to a conventional method to obtain Sample 7. Extract equivalent 2.3 g Cloudy apple juice 850 g Celery juice 70 g Lemon juice 20 g Apple flavor 1.0 g Deionized water Add to a total of 1 kg.

(Prescription of Tomato Juice) After filling a beverage prepared according to the following prescription into a bottle, it is sterilized according to a conventional method.
Sample 8 was obtained. Extract equivalent 2.3 g Tomato juice 950 g Deionized water Add to 1 kg in total.

(Prescription of carbonated beverage) After filling a beverage prepared according to the following recipe into a bottle, it was sterilized according to a conventional method, and a sample 9 was prepared.
And Extract equivalent 2.3 g Fructose-glucose liquid sugar 114.7 g Citric acid 1.5 g Mixed fruit flavor 2.0 g Deionized water Add to a total of 1 kg. (Adjust CO2 gas pressure to 0.15Mpa)

(Prescription of Low Calorie Beverage) A beverage prepared according to the following formulation was filled in a bottle, and then sterilized according to a conventional method.
Sample 10 was obtained. Extract equivalent 2.3 g Erythritol 17.0 g Stevia 0.19 g Citric acid 0.60 g Ume flavor 1.5 g Deionized water Add to a total of 1 kg.

(Sensory Evaluation of Samples 1 to 10)
The taste was evaluated by 15 panelists who were skilled in No. 10. As a control, a control group was prepared by adding an extract equivalent to 0.23% by weight in deionized water, and 5 points were judged to be very unsatisfactory when they felt very delicious compared to the control group. The average of the scoring was determined by taking -5 points when felt. In all of the samples 1 to 10, the palatability was higher than in the control group. Table 7 shows the results.

[0064]

[Table 7]

(Animal Evaluation Experiment of Samples 1 to 10) Sample 2,
Samples 5 and 6 were tested using rats. 3 ml / kg for each of sample 2 and sample 6, and 1.67 ml / kg for sample 5
(Spontaneously hypertensive rats) were orally administered, and the blood pressure lowering activity was measured. Distilled water was used as a control. An experiment was conducted with 6 animals per group in each of the test group and the control group, and the blood pressure lowering activity was measured by the following method. That is, SHR 12-week-old males were purchased from Charles River and preliminarily reared for one week, and then each sample was orally administered intragastrically using a sonde. After 4 hours and 6 hours, the systolic blood pressure was measured by non-invasive blood pressure. It measured with the measuring device (BP-98 by Softron). The rats were kept at 38 ° C. for 10 minutes before the measurement. Table 8 shows the results. From Table 8, it was confirmed that the test group had a statistically significant blood pressure lowering effect than the control group. From the above results, in the case of a human weighing 60 kg, in Sample 2 and Sample 6, 1
It can be expected that the same effect can be obtained by ingesting 80 ml for sample 5 and 100 ml for sample 5, respectively.

[0066]

[Table 8]

(Formulation of alcoholic beverage) Malting malt less than 25% malt (alcohol concentration 5.5 v / v%) is brewed according to a conventional method, and the above-mentioned extract equivalent is 0.11% by weight.
, And filled in a bottle to prepare Sample 11. The sensory evaluation of this sample 11 was performed by nine skilled panelists. As a control, a control group was prepared by adding an extract equivalent to 0.23% by weight in deionized water. The palatability was higher than that of the control group. In addition, in comparison with a normal low-malt beer containing no extract equivalents, it was confirmed that the flavor was slightly sweet and that there was no incongruity in flavor.

(Animal Evaluation Experiment of Sample 11) A test was conducted on Sample 11 using males of SHR (spontaneously hypertensive rat), 26 weeks old. Sample 11 was orally administered at 5.83 ml / kg, and the blood pressure lowering activity was measured. As a control, distilled water and low-malt beer without the above extract were used. The experiment was performed with 6 animals per group in each of the test group and each control group, and the blood pressure lowering activity was measured. Each sample was orally administered intragastrically by sonde,
Six hours later, the systolic blood pressure was measured with a non-invasive blood pressure measuring device (BP-98, manufactured by Softron). The rats were kept at 38 ° C. for 10 minutes before the measurement. The results are shown in Table 9. From Table 9, it was confirmed that the test group had a statistically significant blood pressure lowering effect than the control group. From this result, weight 6
For a 0 kg human, the same effect can be expected if 350 ml of sample 11 is taken.

[0069]

[Table 9]

[0070]

Industrial Applicability The pharmacological composition containing a component exhibiting a blood pressure lowering effect obtained from the fruit body of B. aeruginosa according to the present invention comprises:
Since it shows a blood pressure lowering effect only in a hypertensive model animal and does not show a blood pressure lowering effect in a healthy model animal, it is useful as a safe blood pressure lowering active substance. In addition, by using the artificially cultivated product of the fruit body of Bunakaritake as a raw material,
Pharmaceutical compositions such as inexpensive and stable fruiting body extracts and extracts can be stably produced year-round. Moreover, the beverage produced using the pharmacological composition of the present invention can suppress the occurrence of floc, browning, etc. while maintaining the blood pressure lowering activity.

[Brief description of the drawings]

BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a diagram for explaining a method of cultivating a fungus bed of Beech agaricus which forms fruiting bodies using a translucent cultivation container.

[Explanation of symbols]

 DESCRIPTION OF REFERENCE NUMERALS 1 Bunakaritake cultivation container 2, 2a Bunakaritake primordium 3 Fungus bed 4 Bunakaritake fruit body

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A23L 2/52 A23L 2/38 H 2/38 A61P 9/12 A61P 9/12 43/00 111 43/00 111 C12G 3/00 C12G 3/00 A23L 2/00 F (72) Inventor Tomoe Kawazu 1620 Kurami, Samukawa-cho, Koza-gun, Kanagawa Prefecture Inside the Research Laboratory of Kirin Beverage Co., Ltd. (72) Tomohiko Hori Tsurumi, Yokohama-shi, Kanagawa Prefecture 1-17-1 Ward Wheat Kirin Brewery Co., Ltd. Brewing Laboratory F-term (reference) 2B011 AA07 BA06 BA08 BA13 GA04 GA12 MA11 PA01 4B017 LC03 LG19 LL09 4B018 MD82 ME04 MF01 MF06 MF13 4C088 AA04 AC17 BA09 CA06 CA13 MA52 ZA42 ZC17

Claims (12)

[Claims] 1. A pharmacological composition comprising a component exhibiting a blood pressure lowering effect obtained from a fruit body of B. agaricus. 2. A pharmacological composition containing a component exhibiting a blood pressure lowering effect obtained from a fruit body of B. aeruginosa, comprising, as an active ingredient, an extract or extract exhibiting blood pressure lowering effect obtained from a fruit body of B. aeruginosa. The pharmacological composition according to claim 1, characterized in that: 3. The pharmaceutical composition according to claim 2, wherein the extract or extract is an extract or extract obtained by hot water extraction of fruiting bodies. 4. The pharmacological composition according to claim 2, wherein a dried substance of the fruit body is used as the fruit body. 5. The pharmaceutical composition according to claim 2, wherein the extract or extract is an extract or extract that has been subjected to a purification treatment after hot water extraction. 6. The pharmaceutical composition according to claim 5, wherein the purification treatment is a bentonite treatment and / or an alcohol treatment. 7. The fruit body of B. agaricus as claimed in claim 1, wherein the fruit body of B. agaricus is obtained by artificial cultivation.
7. The pharmacological composition according to any one of items 6 to 6. 8. The pharmacological composition according to claim 7, wherein the artificial cultivation is bacterial bed cultivation. 9. A sterilization step of sterilizing a culture medium in which water is mixed with a nutrient for cultivation including at least one of a water retention body, dried okara and beer lees, and a seed bacterium of B. agaricus on the sterilized medium. And a pre-culturing step of culturing a medium inoculated with a fungus inoculated with B. aeruginosa to obtain a bacterial bed on which the mycelia have grown, and a physical space capable of culturing the bacterial bed and growing into fruiting bodies. A medium culture step of obtaining a Prunus versicolor primordium that has not been exposed to, and a primordia selected from among the Prunus primrose primordia that have not been exposed to the physical space in which the fruiting body can grow, 9. The pharmacological composition according to claim 8, comprising a post-culturing step of culturing under conditions exposed to a physical space in which it can grow to obtain a fruit body of B. agaricus. 10. The pharmacological composition according to claim 1, wherein the blood pressure lowering effect is at least partly a blood pressure lowering effect due to angiotensin I converting enzyme inhibitory activity. 11. A food or drink for preventing and / or improving symptoms of hypertension, which comprises the pharmacological composition according to any one of claims 1 to 10. 12. The hypertension according to claim 11, wherein the food or drink is a drink selected from tea-based drinks, nutritional drinks, fruit / vegetable drinks, carbonated drinks, low-calorie drinks, and alcoholic drinks. Food and drink for prevention of and / or improvement of symptoms.