Blood flow improving agent

Abstract

To provide a blood flow improver that contains reishi mushroom treated with subcritical water.SOLUTION: It has been found out that reishi mushroom treated with subcritical water has great effects of improving a blood flow, improving vascular aging, promoting nitric oxide production, and improving a headache. It also has been found out that the reishi mushroom treated with subcritical water is combined with reishi mushroom not treated with subcritical water, exhibiting remarkable effects of improving a blood flow, improving vascular aging, and improving a headache.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a blood flow improving agent characterized by containing Ganoderma lucidum treated with subcritical water. More specifically, the present invention relates to a vascular aging improving agent, a nitric oxide production promoter, and a headache improving agent, each characterized by containing Ganoderma lucidum treated with subcritical water. The present invention further relates to a blood flow improving agent, a vascular aging improving agent, and a headache improving agent, each characterized by containing both subcritical water-treated Ganoderma lucidum and non-subcritical water-treated Ganoderma lucidum. [Background Art]

[0002] Blood consists of formed elements called blood cells including erythrocytes, leukocytes, and platelets, and plasma as the liquid component. Blood has the transport function of delivering oxygen, nutrients, hormones, and body heat to cells throughout the whole body and collecting carbon dioxide and metabolic wastes, the immune function of protecting the body from bacteria, viruses and other pathogens, and the hemostatic function responding to bleeding. Blood that plays such diverse roles is critical for maintaining human life.

[0003] In recent years, reduced blood flow has become a problem caused by various factors such as lack of exercise, stress, unbalanced diet, smoking, and external environment. Blood flow is regulated by autonomic nerves, hormones, and nitric oxide produced by vascular endothelial cells. Reduced blood flow is known to cause various symptoms including headache, stiff shoulder, low back pain, sensitivity to cold, edema, skin roughness, periodontal disease, and pulmonary thromboembolism. Therefore, preventing reduced blood flow and maintaining smooth blood flow is effective for preventing and improving various symptoms associated with reduced blood flow.

[0004] It is generally known that blood vessels lose elasticity and harden due to aging, lack of exercise, unbalanced diet and other factors. Hardening of blood vessels impairs smooth dilation and contraction of blood vessels, causing reduced blood flow. To prevent reduced blood flow, it is important to prevent vascular aging, that is, the hardening and embrittlement of blood vessels.

[0005] Blood vessels consist of the outer layer, media, and intima. The endothelial cells that make up the intima have the function of regulating blood flow. When nitric oxide is released from endothelial cells, it affects the vascular smooth muscle that makes up the media, relaxing the blood vessels and promoting blood flow. Therefore, to prevent a decrease in blood flow and to improve blood flow, it is important to increase the production of nitric oxide from endothelial cells.

[0006] Headaches are classified into primary and secondary headaches. Primary headaches include migraines, tension headaches, and cluster headaches, and are caused by abnormalities in the function of blood vessels, nerves, muscles, etc. Secondary headaches are headaches that occur as symptoms of diseases such as brain tumors and strokes. The mechanisms of headache onset are complex, but some of the factors involved include vasoconstriction and dysfunction of the pain inhibitory system of the nervous system in tension headaches, and circadian rhythm abnormalities under the control of the hypothalamus, neuropeptides, and blood flow stagnation in cluster headaches (Non-patent Literature 1). In particular, tension headaches are known to account for a large proportion of headaches, and it is thought that preventing vasoconstriction and decreased blood flow and maintaining smooth blood flow is effective in preventing and improving headaches that involve such vascular and other functional abnormalities.

[0007] Subcritical water treatment refers to bringing water in a subcritical state, where the temperature is between 100°C and 374°C and the pressure is above the saturated vapor pressure, into contact with the object to be treated (reishi mushroom in this invention). Subcritical water has excellent component extraction and hydrolysis properties due to its reduced dielectric constant and improved ion product. It has also been reported that subcritical water treatment significantly alters the contained components and properties, and that the changes in components differ depending on the temperature and pressure conditions. For example, it has been reported that subcritical water treatment of sake lees increases solubilized components and enhances radical scavenging activity (Non-Patent Literature 2), that the amount of protein and amino acids in green coffee beans treated with subcritical water increases at 160°C and decreases at higher temperatures (Non-Patent Literature 3), and that subcritical water extraction of green tea reduces astringency compared to hot water extraction (Non-Patent Literature 4). Therefore, it is difficult to predict what kind of component changes or changes in physiological activity will occur as a result of subcritical water treatment.

[0008] Reishi mushroom is a basidiomycete belonging to the genus Ganoderma in the family Ganodermataceae, and is used as a herbal medicine. Regarding the effects of reishi on blood flow, it has been reported that it improves cerebral blood flow in a mouse model of cerebral infarction (Non-Patent Document 5), and a Tie2 activator containing an extract of fermented reishi mushroom has been reported (Patent Document 1). However, this invention differs in that it uses reishi mushrooms treated with subcritical water.

[0009] Regarding the subcritical water treatment of Reishi mushrooms, agents for maintaining the undifferentiated state and promoting the proliferation of stem cells (Patent Document 2), agents for promoting the differentiation of hematopoietic stem cells (Patent Document 3), agents for promoting nutrient transport (Patent Document 4), and agents for activating the immune system (Patent Document 5) have been reported, but no information has been found regarding its effect on improving blood flow. [Prior art documents] [Patent Documents]

[0010] [Patent Document 1] Patent No. 6563827 [Patent Document 2] Patent No. 6535505 [Patent Document 3] Japanese Patent Publication No. 2021-13357 [Patent Document 4] Japanese Patent Publication No. 2021-38169 [Patent Document 5] Japanese Patent Publication No. 2021-38186 [Non-patent literature]

[0011] [Non-Patent Document 1] Katsutaka Hashizume, Psychosomatic Medicine 2016;56(8):833-838 [Non-Patent Document 2] Yoshihisa Wakita, J.Brew.Soc.Japan.2005;100(1):49-55 [Non-Patent Document 3] Masashi Yokota, Science and Technology Research 2014;3(2):121-126 [Non-Patent Document 4] Hideo Eto, Chemistry and Biology 2013;51(7):457-461 [Non-Patent Document 5] Michinori Kubo, Fragrance Journal 1988;88:48-52 [Overview of the project] [Problems that the invention aims to solve]

[0012] In view of the circumstances described above, the present invention aims to provide a material that is excellent in improving blood flow, improving vascular aging, promoting nitric oxide production, and improving headaches. [Means for solving the problem]

[0013] The inventors of this invention conducted extensive research to solve the above problems and discovered that Reishi mushrooms treated with subcritical water have excellent blood flow improving effects, vascular aging improving effects, nitric oxide production promoting effects, and headache relief effects. Furthermore, they found that combining Reishi mushrooms treated with subcritical water and Reishi mushrooms that were not treated with subcritical water showed remarkable blood flow improving effects, vascular aging improving effects, and headache relief effects, leading to the completion of this invention. [Effects of the Invention]

[0014] The present invention provides a blood flow improving agent, a vascular aging improving agent, a nitric oxide production promoting agent, and a headache improving agent characterized by containing subcritical water-treated Reishi mushrooms, which have blood flow improving effects, vascular aging improving effects, nitric oxide production promoting effects, and headache improving effects. Furthermore, the blood flow improving agent, vascular aging improving agent, and headache improving agent containing both subcritical water-treated Reishi mushrooms and non-subcritical water-treated Reishi mushrooms have extremely excellent blood flow improving effects, vascular aging improving effects, and headache improving effects. [Modes for carrying out the invention]

[0015] Ganoderma of the present invention is a basidiomycete belonging to the genus Ganoderma of the family Ganodermataceae, and is used as the crude drug "Reishi". According to ancient Chinese pharmaceutical books including Compendium of Materia Medica and Shennong's Classic of Materia Medica, there exist six types of Ganoderma: red Ganoderma (Chizhi), black Ganoderma (Heizhi), purple Ganoderma (Zizhi), blue Ganoderma (Qingzhi), yellow Ganoderma (Huangzhi) and white Ganoderma (Baizhi). Antler Ganoderma is also known as a type of red Ganoderma. The Ganoderma used in the present invention is not particularly limited as long as it is Ganoderma belonging to the genus Ganoderma of the family Ganodermataceae described above, but Ganoderma lucidum (red Ganoderma) and Ganoderma sinense (also called Ganoderma atrum, Ganoderma japonicum, black Ganoderma) are preferred. A single species or a combination of two or more species may be used, and a combination of red Ganoderma and black Ganoderma is particularly preferred.

[0016] For the Ganoderma of the present invention, those widely distributed in markets such as China and Japan can be used, and wild-grown products or cultivated products may also be used. For the Ganoderma of the present invention, any of fruiting bodies, mycelia, and spores may be used, with fruiting bodies being preferred. Furthermore, dried or pulverized forms of these can be used, or they can be used in fresh form. Extracts obtained by extracting these with a solvent may also be used.

[0017] The subcritical water treatment of the present invention refers to bringing water brought into a subcritical state under predetermined temperature and pressure conditions into contact with a treatment object (Ganoderma lucidum in the present invention). For example, when water is heated to a pressure of 22.1 MPa and a temperature of 374.2° C., it exhibits a state that is neither liquid nor gas. This point is referred to as the critical point of water, and hot water at a temperature and pressure lower than the critical point is referred to as subcritical water. This subcritical water has excellent component extraction effect and hydrolysis effect due to the decrease in dielectric constant and the increase in ion product. Note that the water supplied for subcritical water treatment can be used either in a liquid state or a gaseous state. That is, water vapor, water, or both may be supplied to the treatment tank for subcritical water treatment. In the reaction field during subcritical water treatment, the reaction proceeds more easily in a liquid state than in a gaseous state, so it is preferable to use water forcibly brought into a liquid state in a sealed container. More specifically, a subcritical water treated product can be obtained by placing Ganoderma lucidum, which is the treatment object, and water, which is the treatment agent, in a pressure-resistant container made of metal, ceramics, or the like, sealing the container, and bringing the two into contact with each other for not less than a certain period of time under the subcritical state of water (temperature: 100° C. or higher, pressure: saturated vapor pressure or higher).

[0018] The temperature for subcritical water treatment of Ganoderma lucidum is preferably between 100°C and 300°C, more preferably between 130°C and 200°C, still more preferably between 140°C and 180°C, and most preferably between 160°C and 180°C, for the reason that active ingredients contained in the Ganoderma lucidum treated by subcritical water or the extract thereof can be easily obtained efficiently.

[0019] The pressure for subcritical water treatment of Ganoderma lucidum only needs to be equal to or higher than the saturated vapor pressure at each temperature. For example, the pressure is preferably between 0.1 MPa and 3.0 MPa, more preferably between 0.2 MPa and 1.5 MPa, still more preferably between 0.37 MPa and 1.01 MPa, and most preferably between 0.63 MPa and 1.01 MPa. When the pressure is less than 0.1 MPa, the amount of active ingredients tends to decrease. In addition, excessive pressurization where the pressure of the subcritical water treatment greatly exceeds the saturated vapor pressure requires additional pressurization equipment and improved pressure resistance of the equipment, which deteriorates the economic efficiency of extraction.

[0020] The subcritical water treatment time for Reishi mushrooms is preferably between 5 and 90 minutes, and more preferably between 10 and 30 minutes. If the treatment time is less than 5 minutes, the amount of active ingredients tends to decrease. Also, if the subcritical water treatment time exceeds 90 minutes, it is more likely to cause excessive decomposition of the active ingredients.

[0021] In other words, the subcritical water treatment conditions for Reishi mushrooms are preferably a temperature of 100-300°C, a pressure of 0.1-3.0 MPa, and a duration of 5-90 minutes.

[0022] The subcritical water-treated reishi mushroom used in this invention can be used as is, or it can be used after being dried or pulverized. Alternatively, an extract obtained by adding a solvent to the treated reishi mushroom can be used. These can be concentrated, diluted, filtered, dried, or otherwise processed as needed.

[0023] The Reishi mushroom used in this invention is one that has not undergone subcritical water treatment in any process leading up to its use, and can be dried or pulverized. Furthermore, extracts obtained by adding a solvent can be used. These can be concentrated, diluted, filtered, dried, or otherwise processed as needed.

[0024] The extraction method for obtaining an extract of Reishi mushroom treated with subcritical water or not treated with subcritical water is not particularly limited. For example, it may be a heat extraction method, or a room temperature or cold temperature extraction method. Examples of solvents used for extraction include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (1,3-butylene glycol, propylene glycol, glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, etc.), and ethers (ethyl ether, tetrahydrofuran, propyl ether, etc.). Among these solvents, polar solvents such as water and lower alcohols are preferred, water and aqueous ethanol are more preferred, and water is the most preferred. These solvents may be used individually or in mixtures of two or more. In addition, a solvent whose pH has been adjusted by adding an acid or alkali to the above extraction solvent may be used.

[0025] In the extraction of subcritical water-treated or untreated Reishi mushrooms, the ratio of Reishi to solvent is, for example, 1 to 50% by weight, preferably 5 to 25% by weight, when converted to solid content. For example, by adding water to a dried product of subcritical water-treated or untreated Reishi mushrooms and performing hot water extraction at 95 to 100°C, an extract of subcritical water-treated or untreated Reishi mushrooms can be obtained. Alternatively, by adding a lower alcohol (e.g., ethanol) or a liquid polyhydric alcohol (e.g., propylene glycol, 1,3-butylene glycol) to a dried product of subcritical water-treated or untreated Reishi mushrooms and performing extraction at room temperature (e.g., 5 to 35°C), an extract of subcritical water-treated or untreated Reishi mushrooms can be obtained.

[0026] The subcritical water-treated or untreated Reishi mushrooms, or their extracts, may be used as is in their solution or solvent phase. However, if necessary, and to the extent that it does not affect the effect, the solution or solvent phase may be subjected to treatments such as concentration (concentration by vacuum, membrane concentration, etc.), dilution, filtration, drying (concentration to dryness, spray drying, freeze-drying, etc.), decolorization with activated carbon, deodorization, ethanol precipitation, etc., and the resulting product may be used. In particular, it is preferable to use it in the form of a dried product obtained through the drying treatment.

[0027] The blood flow improving agent of the present invention can be used as a pharmaceutical, quasi-drug, or food. It is preferably administered orally, and can be used in the form of soft capsules, hard capsules, beverages, tablets, candies, gummies, gums, or other food products, or in the form of pharmaceuticals such as powders, granules, tablets, sugar-coated tablets, capsules, syrups, pills, suspensions, liquids, or emulsions. It can also be used as a topical skin preparation, injection, suppository, etc.

[0028] The blood flow improving agent of the present invention may contain other components as needed, within a range that does not impair its effectiveness. It may also contain other medicinal components, such as herbs, vitamins, amino acids, minerals, excipients such as lactose, starch, cellulose, maltitol, and dextrin; surfactants such as glycerin fatty acid esters and sucrose fatty acid esters; film-forming agents such as gelatin, pullulan, shellac, and zein; oils and fats such as wheat germ oil, rice germ oil, and safflower oil; waxes such as beeswax, rice bran wax, and carnauba wax; sweeteners such as sucrose, glucose, fructose, stevia, saccharin, and sucralose; and acidulants such as citric acid, malic acid, and gluconic acid.

[0029] The amount of Reishi mushroom treated with subcritical water or not treated with subcritical water according to the present invention should be taken depending on the form of administration, intended use, age, body weight, etc. For adults, 1 to 20,000 mg, preferably 10 to 5,000 mg, based on the total weight of each dried Reishi mushroom, can be taken orally once to several times a day. In some cases, a smaller amount than the above range may be sufficient, while in other cases, it may be necessary to take more than the range. Regarding the method of adding the active ingredient in the formulation, it may be added beforehand or during manufacturing; the appropriate method should be chosen considering workability.

[0030] The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to these examples. The percentages of content shown in the examples are in weight percentages. [Examples]

[0031] Production Example 1: Hot water extract of red reishi mushroom treated with subcritical water (treatment condition 1). 45g of red reishi mushrooms were placed in a subcritical water treatment tank as the raw material, and subcritical water treatment was performed under treatment conditions 1 (treatment temperature: 140°C, treatment pressure: 0.37MPa, treatment time: 30 minutes). After the subcritical water treatment was completed, 43.8g of subcritical water treated material was obtained by freeze-drying the treated material in the treatment tank. 200mL of purified water was added to 10g of the obtained subcritical water treated material, and extraction was performed at 95-100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 0.6g of hot water extract of subcritical water treated red reishi mushrooms.

[0032] Production Example 2: Hot water extract of red reishi mushroom treated with subcritical water (treatment condition 2). 45g of red reishi mushrooms were placed in a subcritical water treatment tank as the raw material, and subcritical water treatment was performed under treatment conditions 2 (treatment temperature: 160°C, treatment pressure: 0.63 MPa, treatment time: 20 minutes). After the subcritical water treatment was completed, 45.4g of subcritical water treated material was obtained by freeze-drying the treated material in the treatment tank. 200mL of purified water was added to 10g of the obtained subcritical water treated material, and extraction was performed at 95-100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 0.8g of hot water extract of subcritical water treated red reishi mushrooms.

[0033] Production Example 3: Hot water extract of red reishi mushroom treated with subcritical water (treatment condition 3). 45g of red reishi mushrooms were placed in a subcritical water treatment tank as the raw material, and subcritical water treatment was performed under treatment conditions 3 (treatment temperature: 180°C, treatment pressure: 1.01 MPa, treatment time: 30 minutes). After the subcritical water treatment was completed, 39.8g of subcritical water treated material was obtained by freeze-drying the treated material in the treatment tank. 200mL of purified water was added to 10g of the obtained subcritical water treated material, and extraction was performed at 95-100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 2.6g of hot water extract of subcritical water treated red reishi mushrooms.

[0034] Production Example 4: Hot water extract of black reishi mushroom treated with subcritical water (treatment condition 1) 45g of black reishi mushrooms were placed in a subcritical water treatment tank as the raw material for reishi mushrooms, and subcritical water treatment was performed under treatment conditions 1 (treatment temperature: 140°C, treatment pressure: 0.37MPa, treatment time: 30 minutes). After the subcritical water treatment was completed, 41.7g of subcritical water treated material was obtained by freeze-drying the treated material in the treatment tank. 200mL of purified water was added to 10g of the obtained subcritical water treated material, and extraction was performed at 95-100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 0.6g of hot water extract of subcritical water treated black reishi mushrooms.

[0035] Production Example 5: Hot water extract of black reishi mushroom treated with subcritical water (treatment condition 2). 45g of black reishi mushrooms were placed in a subcritical water treatment tank as the raw material for reishi mushrooms, and subcritical water treatment was performed under treatment conditions 2 (treatment temperature: 160°C, treatment pressure: 0.63 MPa, treatment time: 20 minutes). After the subcritical water treatment was completed, 40.3g of the treated material in the treatment tank was freeze-dried to obtain 40.3g of subcritical water treated material. 200mL of purified water was added to 10g of the obtained subcritical water treated material, and extraction was performed at 95-100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 1.0g of a hot water extract of subcritical water treated black reishi mushrooms.

[0036] Production Example 6: Hot water extract of black reishi mushroom treated with subcritical water (treatment condition 3) 45g of black reishi mushroom was placed in a subcritical water treatment tank as the raw material for reishi mushroom treatment, and subcritical water treatment was performed under treatment conditions 3 (treatment temperature: 180°C, treatment pressure: 1.01 MPa, treatment time: 30 minutes). After the subcritical water treatment was completed, 34.2g of subcritical water treated material was obtained by freeze-drying the treated material in the treatment tank. 200mL of purified water was added to 10g of the obtained subcritical water treated material, and extraction was performed at 95-100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 2.4g of hot water extract of subcritical water treated black reishi mushroom.

[0037] Manufacturing Example 7: Mixture of hot water extract of subcritical water-treated red reishi mushroom and hot water extract of subcritical water-treated black reishi mushroom. Two g of the hot water extract of red reishi mushroom treated with subcritical water (treatment condition 3) according to Production Example 3 and two g of the hot water extract of black reishi mushroom treated with subcritical water (treatment condition 3) according to Production Example 6 were mixed uniformly to obtain 4 g of the mixture of the hot water extract of subcritical water-treated red reishi mushroom and the hot water extract of subcritical water-treated black reishi mushroom.

[0038] Manufacturing Example 8: A mixture of subcritical water-treated hot water extracts of red reishi mushroom, subcritical water-treated hot water extracts of black reishi mushroom, and hot water extracts of red reishi mushroom and black reishi mushroom. 1 g of hot water extract of red reishi mushroom treated with subcritical water (treatment condition 3) according to Production Example 3, 1 g of hot water extract of black reishi mushroom treated with subcritical water (treatment condition 3) according to Production Example 6, 1 g of hot water extract of red reishi mushroom from Comparative Production Example 1, and 1 g of hot water extract of black reishi mushroom from Comparative Production Example 2 were mixed uniformly to obtain 4 g of a mixture of hot water extracts of subcritical water-treated red reishi mushroom, subcritical water-treated black reishi mushroom, red reishi mushroom, and black reishi mushroom.

[0039] Production Example 9: 50% ethanol extract of red reishi mushroom treated with subcritical water (treatment condition 3). 45g of red reishi mushrooms were placed in a subcritical water treatment tank as the raw material, and subcritical water treatment was performed under treatment conditions 3 (treatment temperature: 180°C, treatment pressure: 1.01 MPa, treatment time: 30 minutes). After the subcritical water treatment was completed, 39.8g of subcritical water treated material was obtained by freeze-drying the treated material in the treatment tank. 200mL of 50% ethanol aqueous solution was added to 10g of the obtained subcritical water treated material, and extraction was carried out overnight. After filtration, the filtrate was concentrated under reduced pressure and freeze-dried to obtain 2.1g of a 50% ethanol extract of subcritical water treated red reishi mushrooms.

[0040] Production Example 10: 50% ethanol extract of black reishi mushroom treated with subcritical water (treatment condition 3). 45g of black reishi mushrooms were placed in a subcritical water treatment tank as the raw material for reishi mushrooms, and subcritical water treatment was performed under treatment conditions 3 (treatment temperature: 180°C, treatment pressure: 1.01 MPa, treatment time: 30 minutes). After the subcritical water treatment was completed, 34.2g of subcritical water treated material was obtained by freeze-drying the treated material in the treatment tank. 200mL of 50% ethanol aqueous solution was added to 10g of the obtained subcritical water treated material, and extraction was carried out overnight. After filtration, the filtrate was concentrated under reduced pressure and freeze-dried to obtain 1.8g of a 50% ethanol extract of subcritical water treated black reishi mushrooms.

[0041] Comparative Manufacturing Example 1: Hot Water Extract of Red Reishi Mushroom 100g of red reishi mushroom was added to 2L of purified water and extracted at 95-100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 4.4g of hot water extract of red reishi mushroom.

[0042] Comparative Production Example 2: Hot Water Extract of Black Reishi Mushroom 100g of black reishi mushroom was added to 2L of purified water and extracted at 95-100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 4.2g of hot water extract of black reishi mushroom.

[0043] Comparative Production Example 3: Mixture of Hot Water Extracts of Red Reishi Mushroom and Black Reishi Mushroom Two g of hot water extract of red reishi mushroom from comparative manufacturing example 1 and two g of hot water extract of black reishi mushroom from comparative manufacturing example 2 were mixed uniformly to obtain a mixture of red reishi and black reishi hot water extracts totaling four g. [Examples]

[0044] Prescription Example 1: Soft Capsules <Prescription> Component Content (%) 1. Hot water extract of red reishi mushroom treated with subcritical water (treatment condition 3) (production example 3) 10.0 2. Hot water extract of black reishi mushroom treated with subcritical water (treatment condition 3) (production example 6) 10.0 3.Rice germ oil 70.0 4. Beeswax 7.0 5. Vitamin E 3.0 <Manufacturing method> Mix ingredients 1-5, fill a coating made of gelatin, glycerin, and caramel coloring with 250 mg of the mixture, and after drying, obtain soft capsules. <Usage> Take 3 tablets per day.

[0045] Prescription Example 2: Hard Capsules <Prescription> Component Content (%) 1. Hot water extract of red reishi mushroom treated with subcritical water (treatment condition 1) (production example 1) 1.0 2. Hot water extract of black reishi mushroom treated with subcritical water (treatment condition 1) (production example 4) 1.0 3. Cornstarch 90.0 4. Sucrose fatty acid ester 8.0 <Manufacturing method> Mix ingredients 1-4 and fill 250 mg into No. 2 hard capsules to obtain hard capsules. <Usage> Take 4 tablets per day.

[0046] Prescription example 3: Granules <Prescription> Component Content (%) 1. Hot water extract of red reishi mushroom treated with subcritical water (treatment condition 2) (production example 2) 0.1 2. Hot water extract of black reishi mushroom treated with subcritical water (treatment condition 2) (production example 5) 0.1 3.Lactose 89.8 4. Cellulose 10.0 <Manufacturing method> Components 1-4 are granulated by a dry process to obtain granules. <Usage> Intake 1g per day.

[0047] Prescription Example 4: Beverages <Prescription> Component Content (%) 1. Hot water extract of red reishi mushroom treated with subcritical water (treatment condition 3) (production example 3) 1.0 2. Hot water extract of black reishi mushroom treated with subcritical water (treatment condition 3) (production example 6) 1.0 3. Citric acid 6.0 4. Sucrose 10.0 5.Fragrance 1.0 6.Wednesday 81.0 <Manufacturing method> Dissolve ingredients 1-5 in a portion of the water containing ingredient 6 by stirring. Then, add the remaining water containing ingredient 6 and mix. Sterilize the mixture and use it as a beverage. <Usage> Take 50 mL per day.

[0048] Prescription example 5: Tablets <Prescription> Component Content (%) 1. Hot water extract of red reishi mushroom treated with subcritical water (treatment condition 1) (production example 1) 0.1 2. Hot water extract of black reishi mushroom treated with subcritical water (treatment condition 1) (production example 4) 0.1 3.Lactose 70.8 4. Reduced maltose syrup 25.0 5. Sucrose fatty acid ester 4.0 <Manufacturing method> Ingredients 1-5 are mixed and compressed into tablets to obtain 0.5g tablets. <Usage> Take two tablets per day.

[0049] Prescription example 6: Soft capsules <Prescription> Component Content (%) 1. Hot water extract of subcritical water-treated red reishi mushroom, hot water extract of subcritical water-treated black reishi mushroom, and a mixture of hot water extracts of red reishi mushroom and black reishi mushroom (Production Example 8) 20.0 2.Rice germ oil 70.0 3. Beeswax 7.0 4. Vitamin E 3.0 <Manufacturing method> Mix ingredients 1-4, fill a coating made of gelatin, glycerin, and caramel coloring with 250 mg of the mixture, and dry to obtain soft capsules. <Usage> Take 3 tablets per day.

[0050] Comparative Example 1: Conventional soft capsule In the soft capsule formulation of Formulation Example 1, the hot water extract of red reishi mushroom treated with subcritical water (treatment condition 3) (Production Example 3) and the hot water extract of black reishi mushroom treated with subcritical water (treatment condition 3) (Production Example 6) were replaced with rice germ oil to form the conventional soft capsule formulation.

[0051] Comparative Example 2: Conventional soft capsules containing hot water extracts of red reishi mushroom and black reishi mushroom. In the soft capsule formulation of Formulation Example 1, the hot water extract of red reishi mushroom treated with subcritical water (treatment condition 3) (Production Example 3) was replaced with the hot water extract of red reishi mushroom (Comparative Production Example 1), and the hot water extract of black reishi mushroom treated with subcritical water (treatment condition 3) (Production Example 6) was replaced with the hot water extract of black reishi mushroom (Comparative Production Example 2). This resulted in a conventional soft capsule formulation containing hot water extracts of red reishi mushroom and black reishi mushroom. [Examples]

[0052] Test Example 1: Blood Flow Improvement Effect on Human Ingestion Forty men and women (ages 25-60) who regularly complained of coldness and swelling were divided into four groups of 10 each. Group 1 received soft capsules containing hot water extracts of subcritical water-treated red reishi mushroom and subcritical water-treated black reishi mushroom (Formulation Example 1). Group 2 received soft capsules containing a mixture of hot water extracts of subcritical water-treated red reishi mushroom, subcritical water-treated black reishi mushroom, red reishi mushroom, and black reishi mushroom (Formulation Example 6). Group 3 received conventional soft capsules containing hot water extracts of red reishi mushroom and black reishi mushroom (Comparative Example 2). Group 4 received conventional soft capsules (Comparative Example 1). All groups took three soft capsules per day, and blood flow videos were recorded using a blood flow scope before administration and three months after administration. Blood flow velocity was calculated from the obtained videos, and the ratio after ingestion was calculated for each subject, with the pre-ingestion value set at 100.

[0053] Table 1 shows the results of Test Example 1. Compared with Test Group 4 (Comparative Example 1), Test Group 1 (Formulation Example 1), Test Group 2 (Formulation Example 6), and Test Group 3 (Comparative Example 2) showed improved blood flow. Furthermore, Test Group 1 (Formulation Example 1) and Test Group 2 (Formulation Example 6) showed excellent improved blood flow. In particular, Test Group 2 (Formulation Example 6) showed extremely excellent improved blood flow. Therefore, the blood flow-improving effect of Reishi mushroom treated with subcritical water was demonstrated. Furthermore, extremely excellent improved blood flow was demonstrated by combining Reishi mushroom treated with subcritical water and Reishi mushroom that was not treated with subcritical water.

[0054] JPEG0007917900000001.jpg74170

[0055] Test Example 2: Effect of human ingestion on improving vascular aging Fifteen men and women (ages 25-60) were given three soft capsules daily containing a mixture of subcritical water-treated hot water extracts of red reishi mushroom, subcritical water-treated hot water extracts of black reishi mushroom, and hot water extracts of red and black reishi mushroom (Formulation Example 6). Vascular aging deviation scores and vascular age were measured using an acceleration pulse wave measurement system (manufactured by Yumedica Co., Ltd.) before ingestion and three months after ingestion.

[0056] The results of Test Example 2 are shown in Table 2. Higher values ​​for vascular aging deviation and vascular age indicate more advanced vascular aging. Compared to before ingestion, ingestion of the soft capsule formulation (Formulation Example 6) resulted in a decrease in both vascular aging deviation and vascular age. Therefore, the ingestion of a formulation combining subcritical water-treated and untreated Reishi mushrooms demonstrated excellent vascular aging improvement effects.

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[0058] Test Example 3: Headache relief effect on human consumption Forty men and women (ages 25-60) who regularly complained of headaches were divided into four groups of 10 each. Group 1 received soft capsules containing hot water extracts of subcritical water-treated red reishi mushroom and subcritical water-treated black reishi mushroom (Formulation Example 1). Group 2 received soft capsules containing a mixture of hot water extracts of subcritical water-treated red reishi mushroom, subcritical water-treated black reishi mushroom, red reishi mushroom, and black reishi mushroom (Formulation Example 6). Group 3 received conventional soft capsules containing hot water extracts of red reishi mushroom and black reishi mushroom (Comparative Example 2). Group 4 received conventional soft capsules (Comparative Example 1). All groups took three soft capsules per day, and a questionnaire regarding headaches was administered three months after taking the capsules. The questionnaire asked participants to rate the severity of their headaches on one of four scales compared to before taking the medication: "greatly improved," "improved," "slightly improved," or "no change or worsened."

[0059] Table 3 shows the results of Test Example 3. Compared to Test Group 4 (Comparative Example 1), Test Groups 1 (Prescription Example 1), 2 (Prescription Example 6), and 3 (Comparative Example 2) had a larger number of participants who answered "greatly improved," "improved," or "somewhat improved," indicating an improvement in subjective headache symptoms. Furthermore, Test Groups 1 (Prescription Example 1) and 2 (Prescription Example 6) showed excellent improvement in subjective headache symptoms. In particular, Test Group 2 (Prescription Example 6) showed extremely excellent improvement in subjective headache symptoms. Therefore, the headache-improving effect of subcritical water-treated Reishi mushroom was demonstrated, and furthermore, an extremely excellent headache-improving effect was demonstrated by combining subcritical water-treated Reishi mushroom with untreated Reishi mushroom.

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[0061] Test Example 4: Promotion of nitric oxide production in vascular endothelial cells Vascular endothelial cells were cultured in a 10% bovine serum-containing DMEM high-glucose medium at 37°C under 5% CO2 conditions. Then, hot water extracts of red reishi mushroom (Comparative Production Example 1), black reishi mushroom (Comparative Production Example 2), and a mixture of subcritical water-treated red reishi mushroom hot water extract and subcritical water-treated black reishi mushroom hot water extract (Production Example 7) were added to a final concentration of 0.1 mg / mL. After 24 hours of incubation, the supernatant was removed, and Diaminofluorescein-2, a fluorescent probe for nitric oxide detection, was added. The fluorescence intensity of the supernatant was measured, and the fluorescence intensity ratio was calculated with the fluorescence intensity without sample addition set to 100.

[0062] The results of Test Example 4 are shown in Table 4. Hot water extracts of red reishi mushroom (Comparative Production Example 1), hot water extracts of black reishi mushroom (Comparative Production Example 2), and a mixture of hot water extracts of subcritical water-treated red reishi mushroom and subcritical water-treated black reishi mushroom (Production Example 7) showed nitric oxide production promoting activity in vascular endothelial cells.

[0063] Furthermore, a mixture of hot water extracts of subcritical water-treated red reishi mushroom and subcritical water-treated black reishi mushroom (Production Example 7) was shown to have superior nitric oxide production promoting activity compared to hot water extracts of red reishi mushroom (Comparative Production Example 1) and black reishi mushroom (Comparative Production Example 2).

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[0065] Although Production Example 7 is a 1:1 mixture of Production Example 3 and Production Example 6, the nitric oxide production-promoting effect in vascular endothelial cells was also observed when the mixing ratio was set to any ratio within the range of 1:9 to 9:1. Furthermore, when similar tests were conducted on hot water extracts of red reishi mushroom treated with subcritical water (treatment condition 3) (Production Example 3), hot water extracts of black reishi mushroom treated with subcritical water (treatment condition 3) (Production Example 6), 50% ethanol extracts of red reishi mushroom treated with subcritical water (treatment condition 3) (Production Example 9), and 50% ethanol extracts of black reishi mushroom treated with subcritical water (treatment condition 3) (Production Example 10), the nitric oxide production-promoting effect in vascular endothelial cells was also observed. [Industrial applicability]

[0066] Based on the above, the present invention can be used as a blood flow improving agent, a vascular aging improving agent, a nitric oxide production promoting agent, and a headache improving agent containing subcritical water-treated Reishi mushroom. Furthermore, it can be used as a blood flow improving agent, a vascular aging improving agent, and a headache improving agent containing both subcritical water-treated Reishi mushroom and non-subcritical water-treated Reishi mushroom. It can also be used in foods, quasi-drugs, and pharmaceuticals containing these. Moreover, it can be used as an in vitro nitric oxide production promoting agent.

Claims

1. A blood flow improving agent characterized by containing a hot water extract of red reishi mushroom treated with subcritical water (water in a subcritical state at a temperature of 180°C and a pressure of 1.01 MPa) and a hot water extract of black reishi mushroom treated with subcritical water (water in a subcritical state at a temperature of 180°C and a pressure of 1.01 MPa).

2. A vascular aging improving agent characterized by containing a hot water extract of red reishi mushroom treated with subcritical water (water in a subcritical state at a temperature of 180°C and a pressure of 1.01 MPa) and a hot water extract of black reishi mushroom treated with subcritical water (water in a subcritical state at a temperature of 180°C and a pressure of 1.01 MPa).

3. A nitric oxide production enhancer characterized by containing a hot water extract of red reishi mushroom treated with subcritical water (water in a subcritical state at a temperature of 180°C and a pressure of 1.01 MPa) and a hot water extract of black reishi mushroom treated with subcritical water (water in a subcritical state at a temperature of 180°C and a pressure of 1.01 MPa).

4. A headache relief agent characterized by containing a hot water extract of red reishi mushroom treated with subcritical water (water in a subcritical state at a temperature of 180°C and a pressure of 1.01 MPa) and a hot water extract of black reishi mushroom treated with subcritical water (water in a subcritical state at a temperature of 180°C and a pressure of 1.01 MPa).

5. The blood flow improving agent according to claim 1, further containing Reishi mushrooms that have not been treated with subcritical water.

6. The vascular aging improving agent according to claim 2, further containing Reishi mushroom that has not been treated with subcritical water.

7. The headache relief agent according to claim 4, further containing reishi mushrooms that have not been treated with subcritical water.

8. A food composition for improving blood flow, improving vascular aging, promoting nitric oxide production, or improving headaches, containing the agent described in any one of claims 1 to 7.

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