JP4986413B2 - Composition for improving blood circulation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a blood circulation-improving composition having excellent blood circulation-improving effect and further having high safety and practicality and being widely useable for beverages and foods, feed, quasi-drugs, medicines, etc. <P>SOLUTION: The blood circulation-improving composition comprises ellagitannin as an active ingredient. The blood circulation-improving composition comprises at least one selected from a group consisting of elaeocarpusin, chebulagic acid, geraniin and corilagin as ellagitannin as an active ingredient. These ingredients are derived from natural plants having actual results taken in human bodies over a long period, e.g, amla and are free from fear inducing strong adverse action even if they are taken in human bodies in large amounts and have high safety. Therefore, the composition has high practicality and can widely be used for beverages and foods, feed, quasi-drugs, medicines, etc. <P>COPYRIGHT: (C)2007,JPO&amp;INPIT

Description

  The present invention relates to a composition for improving blood circulation containing ellagitannin as an active ingredient, and a food, beverage, feed, quasi-drug, or pharmaceutical product containing the same. Furthermore, the composition for improving blood circulation, wherein ellagitannin is at least one selected from the group consisting of Elaeocarpusin, Keblagic acid, Geraniin, and Corilagin, and It relates to foods, drinks, feeds, quasi-drugs, and pharmaceuticals.

  In recent years, aging, westernization of eating habits, lack of exercise, excessive stress, etc. are major causes of increasing cardiovascular diseases such as arteriosclerosis and cerebral infarction. In such circulatory system diseases, a decrease in blood flow in microvessels has been observed, and it has been pointed out in recent years that this may have various adverse effects on living bodies. Further, in familiar places, the relationship between itching of the skin, fatigue, high blood pressure and the like and blood flow has been pointed out.

  In the human body, blood circulation plays an important role in supplying oxygen and nutrients, and removing carbon dioxide and other metabolic waste products. These two functions are indispensable for the activity and survival of tissue cells. In addition, biological defense functions and immune functions are functions that depend on this blood circulation. Thus, blood circulation is involved in many important biological functions. It has long been recognized that healthy blood circulation is essential for human health. There have also been many reports on the effects of food taken with daily meals on the heart and vascular system.

  As described above, a great deal of attention has been directed to the effects of food on blood circulation and the heart / vascular system, while the importance of blood fluidity has often been overlooked. The reason for this is that, firstly, blood is a “liquid” and it has been assumed that it has “high fluidity”. Second, it is difficult to measure blood fluidity unexpectedly. It was difficult. However, plasma, the “liquid” component of blood, is only about half of the blood component (volume), and the other half is cellular components (red blood cells, white blood cells, platelets; red blood cells mostly). Considering this, it is understood that blood is not always fluid.

  This blood fluidity loses balance due to various factors such as smoking, hypertension, hyperlipidemia, and diabetes. When the symptom progresses, a significant peripheral blood circulation disorder occurs and the tissue becomes abnormal. This also makes it easy to understand that maintaining blood fluidity is essential for health.

  The fact that blood whose half volume is a cellular component can move as if it is “liquid-like” is due to blood viscosity, leukocyte deformability and adhesion, platelet adhesion, and red blood cell deformability. In particular, it is largely due to the deformability of red blood cells. The definition of erythrocyte deformability is not necessarily unified, but it is understood that it is the resistance to erythrocyte shape change, or the mechanical adaptation that erythrocytes exhibit to take on new forms (blood rheology). Recent progress, Medical Review, Inc., 14-56, 1992).

  The effect of red blood cell deformability on blood fluidity is more directly important when the blood vessel is a capillary vessel. The diameter of the capillary is about 5 μm on average, although it varies depending on the tissue. On the other hand, the diameter of red blood cells (biconcave disk) is about 8 μm for humans. Therefore, it is clear that erythrocytes cannot pass through capillaries unless they are deformed. Therefore, the deformability of erythrocytes is the most important factor that affects the blood flow velocity or blood flow of capillaries, and it can be said that it is the basic mechanism of blood fluidity.

Attention is now being focused on the mechanism by which red blood cell deformability is maintained and how it is affected by environmental factors such as diet. Therefore, ingestion of foods and food ingredients that have an effect of improving blood flow is considered to be effective in preventing blood flow reduction, which is considered to be one of the causes of various diseases including cardiovascular diseases. It is thought that it can contribute to prevention and health promotion. In addition, many foods and food ingredients that have the potential to improve blood flow have been reported so far, and specific examples thereof include umeboshi, plum extract (see, for example, Patent Document 1), black vinegar ( For example, refer to Patent Document 1) and Tartary soba.
However, all of these compositions have problems in flavor and properties, and could not be widely applied to foods.

  In addition to blood fluidity, a major risk factor that inhibits blood circulation is the formation of a thrombus, and the main factors for forming a thrombus include platelet aggregation and blood coagulation.

  A thrombus can be formed into an insoluble polymer together with platelets, leukocytes and the like and solidified on the inner wall of a blood vessel while a protein called fibrinogen is activated and converted into fibrin. When the body is normal, the fibrinolytic enzyme that works to dissolve fibrin, which is the source of the thrombus, prevents thrombus. If the fibrinolytic enzyme is insufficient, fibrin cannot be dissolved and a thrombus can be formed.

  The formed thrombus is deposited in the blood vessels, reducing the cross-sectional area of the blood vessels and inhibiting blood circulation, so that the blood cannot normally supply nutrients and oxygen in the cells and tissues, and the cells In addition, the waste of tissues cannot be discharged, and problems such as accumulation of toxicity will occur.

  In blood vessels, the symptom caused by a blood component mass called thrombus is called thrombosis in a broad sense (hereinafter simply referred to as “thrombosis” in a broad sense). The pathology that occurs is divided into thrombosis and embolism in a narrow sense. In the narrow sense, thrombosis is a symptom caused by partial or complete blockage of blood flow at the site where the thrombus is formed, and embolism is caused by removal of the thrombus from the formation site and movement by the blood flow. It refers to a pathological condition caused by physical or complete occlusion.

  Such thrombosis induces various diseases depending on the site of the blood vessel where the thrombus has occurred. In particular, serious symptoms such as stroke, cerebral hemorrhage, cerebral infarction, heart failure, myocardial infarction, heart palsy occur when it occurs in the cerebral blood vessel or cardiovascular, causing half-body involuntary and death in severe cases is there.

  Currently, in order to solve thrombosis, research and development of antithrombotic agents and thrombus formation preventive agents that suppress the formation of thrombus and thrombolytic agents that dissolve the generated thrombus are mainly conducted.

  As an antithrombotic agent or an agent for preventing thrombus formation, there are aspirin that inhibits blood coagulation by inhibiting adhesion of platelets to the blood vessel wall and aggregation of platelets, and heparin (Heparin) that blocks the endogenous blood coagulation pathway in the body. ), Coumarin, etc. are currently used in clinical practice. Recently, eicosapentaenoic acid (EPA), prostacycline (PG12) derivatives and the like have been commercialized. However, since these drugs have no specificity, they may affect parts other than the thrombus in the living body, and may cause bleeding or the like when remaining in the living body. In addition, antithrombotic activities such as hirudin, synthetic antithrombin, and ticlopidin have been reported, but have not yet been put into practical use.

  As a thrombolytic agent, a plasminogen activator (plasminogen activator) such as streptokinase or urokinase is intravenously injected into a patient in which a thrombus has been generated to activate the thrombolytic system in the body. Is commonly used. The effect of dissolving thrombus has been proved in many clinical experiments, but, like antithrombotic agents or antithrombotic agents, it has no specificity for thrombus and has side effects such as general bleeding during the treatment of thrombus. is there. Tissue-type plasminogen activator (tPA) is considered to be an ideal thrombolytic agent because of its high selectivity for thrombus. However, as a result of actual application to clinical treatment, There were still side effects such as systemic bleeding. In addition, since the half-life in the blood is very short and the duration of the drug is short, the dose must be large in order to maintain the drug in the body, so the treatment cost is much higher than that of conventional thrombolytic agents. There is a problem that it is expensive.

  Although these medicines are used to prevent the formation of blood clots, they do not show a significant effect on thrombus removal and induce serious side effects. Research on ingredients or food ingredients having a function of preventing or regulating or activating the constitution has also attracted attention.

  As food ingredients, materials such as nattokinase, polyunsaturated fatty acids, glucosamine, and onion thin skin (see, for example, Patent Document 2) are known, but there are problems with flavor and properties, and they are widely applied to food. could not.

  Moreover, although the patent about kiwifruit extract (for example, refer patent document 3) was published, there exists a fault that the activity in a neutral region is weak.

  On the other hand, in recent years when people who live with pets tend to increase, there are many cases where pets are kept indoors, and it is inevitably in an environment where it is difficult to do free exercise. In addition, it is said that the environment for animal medicine has improved and the aging of society has progressed. Furthermore, it is said that the stress is on the pets as well as modern people. Moreover, in livestock called industrial animals, overcrowded breeding in a narrow space is indispensable due to the pursuit of efficiency for cost reduction. Under such circumstances, there are concerns about deterioration of blood circulation and various diseases caused by excessive stress load, and there is a growing social demand for feed that can maintain animal health and prevent diseases. .

JP-A-11-228561 JP 2002-171934 A JP 2003-171294 A

  By the way, even if a food / food ingredient that can be expected to have an effect of improving blood flow and antithrombotic (inhibition of platelet aggregation and blood coagulation) is found, if there are difficulties in flavor and properties, it will eventually be widely used in foods, etc. It cannot be applied to. Therefore, from the viewpoint of practicality, it is desirable that the flavor, properties, etc. have few difficulties. Furthermore, from the viewpoint of safety, it is desirable that there is no risk of inducing strong side effects even if a large amount is ingested.

  The present invention has been made in view of the above problems, and its purpose is that it has excellent blood circulation improvement effect, and since it has high safety and practicality, food and drink, feed, quasi drug, An object of the present invention is to provide a composition for improving blood circulation that can be widely used in medicines and the like. Another object of the present invention is to provide foods and drinks, feeds, quasi-drugs, and pharmaceuticals containing the above-described excellent blood circulation improving composition.

  Therefore, the inventors of the present invention have studied and studied from various perspectives for the purpose of searching for blood circulation improving components from various substances. As a result, the blood flow improving effect, platelet aggregation inhibiting effect and blood coagulation inhibiting effect superior to ellagitannin are found. I discovered something new. Furthermore, it was newly found that elaeocalpsin, keblagic acid, geraniin and corilagin have a significant blood flow improvement effect, a platelet aggregation inhibitory effect and a blood coagulation inhibitory effect. Accordingly, the inventors of the present application have further developed this new knowledge and completed the following invention.

  That is, the gist of the present invention is a composition for improving blood circulation comprising ellagitannin as an active ingredient. Furthermore, the gist thereof is a composition for improving blood circulation, which contains at least one selected from the group consisting of elaeocalpsin, keblagic acid, geraniin and corilagin as an active ingredient. Since this composition has an excellent effect of improving blood fluidity and suppressing platelet aggregation and blood coagulation, it can prevent the occurrence of blood circulation disorder and blood coagulation. Moreover, this composition is derived from a natural plant that has been ingested by humans over a long period of time, and even if it is ingested in large quantities, there is no risk of inducing strong side effects and it is highly safe. Therefore, the composition is highly practical and can be widely used in foods and drinks, feeds, quasi drugs, pharmaceuticals, and the like.

  Furthermore, the gist thereof includes foods and drinks, feeds, quasi-drugs, and pharmaceuticals characterized by containing the composition for improving blood circulation.

  The “blood flow improving effect” in the composition for improving blood circulation of the present invention can be evaluated by, for example, a technique using a blood vessel model as described below. That is, the composition for improving blood flow of the present invention is added to the collected blood, and this is used as test blood. On the other hand, the additive-free blood is used as control blood.

  These two kinds of blood are flowed at a difference of 20 cm in water column using MC-FAN (both manufactured by Hitachi Haramachi Electronics Co., Ltd.) in Bloody 6-7, which is a finely processed flow path of a blood vessel model. And, the time for each blood to pass through the flow path is obtained as a blood flow passage time, and the blood flow improvement can be evaluated by comparing the blood flow passage time of the test blood and the blood flow passage time of the control blood. it can. In this comparison, if the blood flow passage time of the test blood is shorter than the blood flow passage time of the control blood, it can be determined that blood flow improvement has been observed.

  In addition, by setting a test in which a substance that induces thrombus, such as lipopolysaccharide, is added to the test blood and the target blood, and measuring these, the blood flow improving effect on the substance that worsens the blood flow is evaluated. be able to.

  Alternatively, blood flow improvement can be evaluated by determining and comparing the speed (blood flow speed) at which each blood passes through the flow path. In this comparison, if the blood flow velocity of the test blood is higher than the blood flow velocity of the control blood, it can be determined that blood flow improvement has been observed.

  The “platelet aggregation inhibitory activity” in the composition for improving blood circulation of the present invention can be evaluated by a technique such as a platelet aggregation test. That is, using a platelet aggregometer, after adding a sample to the blood of a healthy person, adding a substance that induces aggregation, and measuring the platelet aggregation rate after a certain time, the platelet aggregation rate of the test blood By comparing the platelet aggregation rate of the control blood with that of the control blood, the activity can be evaluated. In this comparison, if the platelet aggregation rate of the test blood is smaller than the platelet aggregation rate of the control blood, it can be determined that the platelet aggregation inhibitory activity was observed.

  The “blood coagulation inhibiting effect” in the composition for improving blood circulation of the present invention can be evaluated by, for example, the following method. That is, from the result of measuring the activated partial thromboplastin time (APTT), by comparing the blood clotting time of the test blood with the blood clotting time of the control blood, the factors involved in the intrinsic pathway are determined. It can be activated to evaluate the effect of inhibiting fibrin formation and suppressing thrombus formation in blood vessels. In this comparison, if the blood coagulation time of the test blood is longer than the blood coagulation time of the control blood, it can be determined that the blood coagulation inhibitory effect has been recognized.

  Therefore, according to the present invention, in addition to having an excellent blood circulation improvement effect, the composition for improving blood circulation can be widely used for food and drink, feed, quasi-drugs, pharmaceuticals, etc. because of its high safety and practicality. Things can be provided.

  Moreover, food / beverage products, feed, quasi-drugs, and pharmaceuticals containing the above-described excellent blood circulation improving composition can be provided. For this reason, it is possible to alleviate, ameliorate, or prevent a blood circulation disorder by improving blood circulation, and it is possible to alleviate, ameliorate, or prevent a circulatory system disease caused by the blood circulation disorder.

  Hereinafter, the composition for improving blood circulation according to an embodiment of the present invention, and foods and drinks, feeds, quasi drugs, and pharmaceuticals containing the same will be described in detail.

  The ellagitannins of the present invention are hydrolyzed to polyhydric phenol acids and polyhydric alcohols (such as sugars) by alkalis and enzymes, and the distribution is localized in dicotyledonous flowering plants. And ellagic acid, a dimer thereof, has a chemically bonded structure, and is classified as a hydrolyzable tannin. Specific examples of the compound are known as geraniin, elaeocarpsin, keblagic acid, corilagin, embricanin, punygluconin, peduncuragine, etc., and preferred ones are geraniin, elaeocarpsin, keblagic acid, corilagin. is there.

  All of these compounds can be chemically synthesized, but they are substances contained in natural plants, and those extracted from natural plants that have been ingested by humans over a long period of time are preferred from the viewpoint of safety.

  Examples of plants that have been reported to contain ellagitannins include Amera of Euphorbiaceae, Akamegashiwa, Chankapiedra, Ganoderma of Owlaceae, Momotamana of Chikunushi, Mochicha of Rosaceae, Sanshuyu of Mizukiaceae, walrus of Azalea , Maple family megsurinoki, urushiaceae quintuplet, misogi family banaba, rose family walnut mushroom, pomegranate family pomegranate, but the knowledge of the physiological effects of these plants is diarrhea prevention, kidney stone prevention, anti-allergy Although it has been reported that the increase in blood glucose level is suppressed, the effect of improving blood circulation has not been reported.

  The origin of Elaeocarpusin is not particularly limited, but Amler (Scientific name: Phyllanthus embilica, Euphorbiaceae), Megusurinoki (scientific name: Acer nicoense Maximiwicz, including moss) It is known that any plant can be used as an extraction raw material.

The origin of chebulagic acid is not particularly limited, but it may be contained in plants such as Amler (scientific name: Phyllanthus embilica) and Momotana (scientific name: Terminaria catappa, Cykundeidae). Any plant can be used as an extraction raw material.
The origin of geraniin is not particularly limited, but Amler (scientific name: Phyllanthus embilica, Euphorbiaceae), Akamegasiwa (scientific name: Mallatus japonica, eusaceae) Family) and Gennoshouko (scientific name: Geranium nepalense var. Thumbergii, Owlaceae) and the like, and any plant can be used as an extraction raw material.
The origin of corilagin is not particularly limited, but Amler (scientific name: Phyllanthus embilica, Euphorbiaceae), Momotamana (scientific name: Terminata catappa), walrus (scientific name: aphtos (scientific name: aphtos) It is known to be contained in plants such as Azalea), and any plant can be used as an extraction raw material.

  The natural plant used as an extraction raw material for the composition for improving blood circulation of the present invention is not particularly limited as long as it is a plant containing the compound as described above, but Amler containing all the components is preferable.

  Amler is a deciduous sub-tree that belongs to the genus Euphorbiaceae, and is distributed from India to the Malaysian region and southern China, and India is considered the origin. In addition, Amler has a unique name for each region or language, such as citrus, oil sweets, Satsuma mushrooms, Emblic Mirobaran, Armaraki, Malacca, Malacca Tree, Indian Gooseberry, Aronra, Amira. , Amiraki, Amira Cattra, Nerikai, Neruri, Tasha, Kayuraka, Kemuraka, Nakhon Pong and others.

  Although it has been known that ellagitannin, ellaeocarpsin, keblagic acid, geraniin and corilagin exist in the above plants, there has never been a specific report regarding the fact that they have an effect of improving blood circulation. Was newly discovered after extensive research.

  Here, ellagitannin can be used as it is, or an extract such as a water extract or an alcohol extract, or an enzyme treated with these extracts.

  In order to extract and prepare the compound from natural plants, conventional means used for separation and purification of natural polyphenols containing glycosides are appropriately employed. Common means include, for example, extraction, concentration, filtration, liquid separation, fractional precipitation, crystallization, honey, vacuum drying, freeze drying, adsorption chromatography, reverse phase chromatography, hydrophobic chromatography, gel filtration chromatography. , Ion exchange chromatography, thin layer chromatography and the like. Fractions obtained by fractionating the source extract of the compound by an appropriate method selected from the conventional methods as described above are selected and combined, and if necessary, further appropriate methods are used. By repeating the operations of fractionation, selection and combination, the compound purified to a desired level can be obtained. The compound thus obtained can be used in the form of a composition by mixing with other appropriate components, if necessary, and can be used in an appropriate degree of purification and form depending on the purpose. A preparation of the compound may be used.

  In the extraction of the compound from a natural plant, it is preferable to use an enzyme treatment together, and this treatment can improve the yield and flavor, and can obtain a component having a high blood circulation improvement effect. The enzyme treatment may be performed before extraction or at the time of extraction. The pH at which the enzyme treatment is performed can be appropriately set using the optimum pH and pH stability of the enzyme used as an index. Also, the temperature at which the enzyme treatment is performed can be appropriately set using the optimum temperature and temperature stability of the enzyme to be used as an index.

  The enzyme used for the enzyme treatment of the present invention is not particularly limited, but is preferably a hydrolase frequently used in the food industry. This is because this type of enzyme has been used and is preferable from the viewpoint of safety and the like. Specific examples of the enzyme include hydrolytic enzymes such as pectinase, amylase, protease, lipase, tannase, dextranase, cellulase, hemicellulase, trypsin, and papain. Among these, it is preferable to use one type selected from pectinase, protease, tannase and cellulase, or to use two or more types in combination. According to this, the extraction efficiency can be further improved.

  Extracts and fractions from plants can be used as they are, but they can also be used after being dried and powdered by means such as spray drying or freeze drying, if necessary.

  The content ratio of elaeocarpsin, keblagic acid, geraniin and corilagin in the active ingredient ellagitannin is 5-80% by weight and 5-80% by weight of ellaeocarpsin in terms of blood flow improving effect. %, Geraniin 5-80%, corilagin 5-80%, respectively, preferably 10-40% elaeocarpsin, 10-40% quebramic acid, 10-40% geraniin It is more preferable to contain 10 to 40% of corilagin, respectively, 15 to 35% of elaeocalpsin, 15 to 35% of keblagic acid, 15 to 35% of geraniin, and 15 to 35% of corilagin It is most preferable that each be contained in the range of.

  The composition for improving blood circulation in the present invention can be used for the purpose of alleviating, improving or preventing blood circulation disorders. Examples of symptoms or diseases related to the blood circulation disorder include Raynaud's phenomenon, Raynaud's disease, Raynaud's syndrome, itching of the skin, fatigue, malaise, hyperlipidemia, arteriosclerosis, myocardial infarction, cerebral infarction, hyperemia, congestion. , Bleeding, anemia, dark redness around the skin, mucous membranes, nails, lips, eyes, etc., itchy skin, bleeding tendency, easy bruising, dizziness, hot flashes, bloody blood (nosebleed), hemoptysis, vomiting, melena, Examples thereof include hematuria, muscle pain, nausea, gastric sensation, and blood flow disorder observed in insomnia. It has been clarified that blood flow reduction is observed in the symptoms or diseases listed here, and a desired effect can be expected by improving the blood flow with the composition for improving blood circulation of the present invention. Specific examples of fatigue include stiff shoulders and low back pain, and coldness is also included as one aspect thereof.

  The composition for improving blood circulation of the present invention can be widely applied to foods and drinks, feeds, quasi-drugs, pharmaceuticals, etc., but is particularly preferably applied to foods and drinks that can be easily consumed by humans.

  The food / beverage products in the present invention are not particularly limited as long as they can be taken orally, such as solutions, suspensions, powders, solid moldings and the like. Specific examples of food and drink include, for example, instant noodles, retort foods, canned foods, microwave foods, instant soups and miso soups, freeze-dried foods, soft drinks, fruit juice drinks, vegetable drinks, soy milk drinks, coffee Beverages, tea beverages, powdered beverages, beverages such as concentrated beverages, nutritional beverages, alcoholic beverages, bread products such as bread, pasta, noodles, cake mix, fried flour, bread crumbs, rice cakes, caramel, chewing gum, chocolate, cookies, Seasonings such as biscuits, cakes, pies, snacks, crackers, Japanese confectionery, dessert confectionery, sauces, tomato processed seasonings, flavor seasonings, cooking mixes, sauces, dressings, soups, curry stew , Processed fats and oils, butter, margarine, mayonnaise and other fats, milk beverages, yogurts, lactic acid bacteria beverages, ice cream Milk products, creams and other dairy products, frozen foods, fish ham and sausages, fishery processed products such as fish paste products, livestock processed products such as livestock ham and sausages, canned agricultural products, jams and marmalades, pickles, boiled beans, cereals And other processed agricultural products, nutritional foods, tablets, capsules and the like.

  The intake amount of the composition for improving blood circulation of the present invention as a food or drink is not particularly limited, but should be adjusted according to the disease state of the present invention, the body weight, age, constitution, physical condition, etc. of the sick, The composition for improving blood circulation per day can be appropriately set within the range of 10 mg to 10 g, preferably 40 mg to 5 g. The above-mentioned food and drink can be taken in one to several times a day depending on the state of illness or food.

  The feed in the present invention refers to food for feeding to organisms other than humans, and the form thereof is not particularly limited. The organism to which the feed can be applied is not particularly limited, and examples thereof include farm animals and pet animals. Examples of farmed animals include domestic animals such as horses, cows, bras, sheep, goats, camels and llamas, laboratory animals such as mice, rats, guinea pigs and rabbits, and poultry such as chickens, ducks, turkeys and ostriches. is there. Examples of pet animals include dogs and cats.

  The quasi-drugs and pharmaceuticals in the present invention refer to those prepared as oral preparations or injections according to conventional methods using excipients and other additives suitable for oral or parenteral administration. Preferred quasi-drug and pharmaceutical embodiments are oral formulations, most preferred are oral solid formulations. This is because oral solid preparations can be easily taken and are convenient to store and carry.

  Examples of oral solid preparations include tablets, powders, fine granules, granules, capsules, pills, sustained release agents and the like. The oral solid preparation of the present invention comprises an appropriate pharmacologically acceptable carrier, excipient (eg starch, lactose, sucrose, calcium carbonate, calcium phosphate etc.), binder (eg starch, gum arabic, carboxymethylcellulose, Hydroxypropylcellulose, crystalline cellulose, alginic acid, gelatin, polyvinylpyrrolidone, etc.), lubricants (eg, stearic acid, magnesium stearate, calcium stearate, etc.), disintegrating agents (eg, carboxymethylcellulose, talc, etc.), etc. for improving blood flow It is obtained by mixing with a composition and solidifying.

  In addition, oral liquid preparations include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs, etc., and generally used inert diluents such as purified water, The thing containing ethyl alcohol. The oral liquid preparation of the present invention further contains adjuvants such as wetting agents and suspending agents, sweeteners, flavors, fragrances, preservatives and the like in addition to the blood circulation improving composition and diluent. May be.

  In this invention, when processing into the blood circulation improvement composition or the food-drinks containing it, various nutrient components can be strengthened.

Nutritional ingredients that can be strengthened include vitamins such as vitamin A, vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, vitamin D, vitamin E, niacin (nicotinic acid), pantothenic acid, folic acid, Essential amino acids such as lysine, threonine and tryptophan, peptides such as L-theanine, soybean peptide, and egg-derived peptide, minerals such as calcium, magnesium, iron, zinc and copper, and, for example, α-linolenic acid, EPA, Substances that contribute to human health such as DHA, evening primrose oil, octacosanol, casein phosphopeptide (CPP), casein calcium peptide (CCP), water-soluble dietary fiber, insoluble dietary fiber, oligosaccharides, and other foods and food additives One or more of the useful substances approved as .

  The dose of the composition for improving blood circulation of the present invention as a pharmaceutical is appropriately determined according to individual cases in consideration of the administration route, disease symptoms, age of the administration subject, sex, etc. The active ingredient per person is about 10 mg / day to 10 g / day, preferably 40 mg / day to 5 g / day.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, a following example does not limit the scope of the present invention.

[Example 1] Preparation of composition for improving blood circulation 1
The dried Amler fruit was crushed and sieved to 40 mesh or less, 2 L of distilled water was added to 100 g of the powder, 0.1 g of pectinase and 0.1 g of tannase were added, and extraction was performed at 55 ° C. for 2 hours. Thereafter, the enzyme was inactivated at 90 ° C. for 30 minutes. Thereafter, the enzyme-treated solution is centrifuged (3000 rpm, 10 minutes), the supernatant is filtered, the filtrate is further spray-dried, and the Amler enzyme extract (Composition A for improving blood circulation A containing 29% ellagitannin) is obtained. ) 45 g was obtained.

[Example 2] Preparation of composition for improving blood circulation 2
Amler juice was obtained from Amler fruit. The production method is not particularly limited. For example, Amler fruit juice (Composition B for improving blood circulation (solid content 10%)) can be obtained by squeezing Amler fruit with a squeezing machine. . The solid content of the composition B for improving blood circulation contained 27% of ellagitannin.

[Example 3] Preparation of composition for improving blood circulation 3
After pulverizing the dried leaves of Gennosho and dried tea leaves, they were sieved to 40 mesh or less, 2 L of distilled water was added to 100 g of each powder, and extraction was performed at 55 ° C. for 3 hours. Thereafter, the extract is centrifuged (3000 rpm, 10 minutes), the supernatant is filtered, the filtrate is freeze-dried, 26.8 g of Genokosho extract (blood circulation improving composition C), and tea extract (blood Circulation improvement composition D) 22.3 g was obtained. The composition C for improving blood circulation and the composition D for improving blood circulation contained 25% and 18% of ellagitannin, respectively.

[Test Example 1] Confirmation of blood flow improvement effect 1
In order to confirm the blood flow improvement effect of the composition for improving blood circulation of the present invention, the change in blood flow rate (μL / sec) when the composition for improving blood circulation was added to human blood was investigated.

  Using a vacuum blood collection tube (manufactured by Terumo Corp .: treated with heparin sodium), blood was collected from the mesenteric vein of a healthy subject in a sitting position at rest. The obtained blood (test blood) was dispensed 1 mL at a time, and the composition A for improving blood circulation, the composition B for improving blood circulation, and the composition C for improving blood circulation obtained in Examples 1, 2, and 3. Then, 4 μL of each solution prepared by adjusting the blood circulation improving composition D with a physiological saline solvent so as to have a final concentration of 1 μg / mL was added to the measurement. On the other hand, as a control blood (control), a solution to which 4 μL of physiological saline as a solvent was added was prepared and subjected to measurement in the same manner.

  In addition, a test group in which 4 μg / mL of lipopolysaccharide (hereinafter referred to as LPS) that induces thrombus was added to the test blood and a test group in which the same amount of LPS was added to the control blood were set, and these were also measured. It was used for.

  The blood flow velocity was measured using MC-FAN (manufactured by Hitachi Haramachi Electronics Co., Ltd.). In addition, as a microfabricated flow path of a blood vessel model for allowing blood to pass, 8736 parallel grooves forming a fine groove having a flow path depth of 4.5 μm, a flow path width of 7 μm at the center of the depth, and a flow path length of 30 μm A silicon single crystal substrate on which a microchannel array is arranged (Bloody 6-7; manufactured by Hitachi Haramachi Electronics Co., Ltd.) was used. And 100 microliters of blood was poured by 20 cm water column difference, and the whole blood passage time was measured as blood flow passage time. At the same time, the state of blood flow was recorded with a microscope-video camera system. As the measurement values, the average value of all three measurements was used. The obtained blood flow passage time was corrected by setting the time required for 100 μL of physiological saline to pass through to 12 seconds. Based on this correction value, the blood flow velocity (μL / second) was obtained by calculation. The results are shown in Table 1.

[Test Example 2] Confirmation of blood flow improvement effect 2
Furthermore, in order to confirm the blood flow improving effect of elaeocalpsin, ketebraic acid, geraniin and corilagin, changes in blood flow velocity (μL / sec) when they were added to human blood were investigated.

  Measurement was performed in the same manner as in Test Example 1 using a sample prepared by adjusting elaeocalpsin, keblagic acid, geraniin, and corilagin with a physiological saline solvent to a final concentration of 0.1 μg / mL. The results are shown in Table 2.

  In the control in which the composition for improving blood circulation of the present invention was not added, the blood flow rate was 1.55 μL / second, whereas in the test group to which the elaeocalpsin of the present invention was added, the blood flow rate was 2 .53 μL / sec. In other words, since the blood flow velocity was increased by the addition of the elaeocalpsin of the present invention, the existence of a blood flow improvement effect was demonstrated. Moreover, in the two test groups to which LPS for inducing thrombus was added, the blood flow velocity was slower than that of the control. However, in the test group to which the elaeocalpsin of the present invention was added, the blood flow velocity was about 10 times faster than the test group that was not. This means that the elaeocalpsin of the present invention has an effect of improving blood flow in a state where thrombi are easily formed. By the way, the same result was obtained when the same test was performed using ketebraic acid, geraniin, and corilagin.

[Example 4] Preparation of composition for improving blood circulation 4
The dried Amler fruit was crushed and sieved to 40 mesh or less, 2 L of distilled water was added to 80 g of the powder, and extraction was performed at 55 ° C. for 3 hours. Thereafter, the extract was centrifuged (3000 rpm, 10 minutes), the supernatant was filtered, and the extract and the residue were separated. Distilled water (2 L) was added to the residue and extraction was repeated once more under the same conditions. The extracts were combined and then lyophilized to obtain 35.0 g of Amler extract powder containing about 30% ellagitannin.

  Acetone extract obtained by adding 60% acetone to the obtained Amler extract powder and performing extraction at 25 ° C. for 3 hours was subjected to column chromatography such as Toyopearl HW-40, MCL gel CHP 20P, Sephadex LH-20, Chromatorex ODS and the like. The blood flow improving compositions E, F, G and H of the present invention were obtained.

  The obtained compositions E, F, G, and H were examined in accordance with conventional methods such as NMR, GC-MS, and IR spectrum, and as a result, each of them contained elaeocalpsin, keblagic acid, geraniin, and corilagin as main components. found. Moreover, the content was 95%, 96%, 96%, and 94%, respectively.

[Test Example 3] Confirmation of blood flow improvement effect 3
In order to confirm the blood flow improvement effect of the compositions E to H for improving blood circulation of the present invention obtained in Example 4, measurement was performed in the same manner as in Test Example 1.

  Table 3 shows the results obtained by measuring the blood circulation improving compositions E to H of the present invention obtained in Example 4 with distilled water and adjusting them to 0.1 μg / ml as samples. It was.

  In the control in which the composition for improving blood circulation according to the present invention was not added, the blood flow velocity was 1.55 μL / sec, whereas the composition for improving blood circulation according to the present invention E (Elaeo Calpsin) was added. In the test group, the blood flow velocity was 2.43 μL / second. That is, the blood flow velocity was increased by the addition of the composition for improving blood circulation E (Eraeocalpsin) of the present invention, so the existence of the blood flow improving effect was demonstrated. Moreover, in the two test groups to which LPS for inducing thrombus was added, the blood flow velocity was slower than that of the control. However, the blood flow velocity of the test group to which the composition E for improving blood circulation of the present invention was added was about 10 times faster than the test group that was not. This means that the composition for improving blood circulation E (Elaeocalpsin) of the present invention has an effect of improving blood flow in a state where thrombi are easily formed. By the way, when the same test was performed using the composition F (keblagic acid), G (geraniin), and H (collagin) for improving blood circulation, similar results were obtained.

[Test Example 4] Confirmation of blood flow improvement effect 4
Furthermore, in order to confirm the blood flow improving effect of the composition for improving blood circulation according to the present invention at a low concentration, the concentration of the composition for improving blood circulation is changed to change the blood flow velocity (μL / second) in the same manner. investigated.

  The test was conducted in the same manner as in Test Example 1, except that the final concentrations of the blood circulation improving compositions E to H of Example 4 added to the test blood were 20 ng / mL, 40 ng / mL, and 100 ng / mL. It was. The results are shown in Table 4.

  In the control in which the composition for improving blood circulation of the present invention was not added, the blood flow rate was 1.58 μL / second, whereas in the test group to which the composition for improving blood circulation of the present invention E was added, the blood flow rate was The speeds were 1.85 μL / sec, 2.12 μL / sec, 2.41 μL / sec, respectively. In other words, the addition of the composition E for improving blood circulation according to the present invention increases the blood flow velocity in a concentration-dependent manner, demonstrating the existence of a blood flow improving effect. Similarly, the addition of the blood circulation improving compositions F to H of the present invention increases the blood flow velocity in a concentration-dependent manner, demonstrating the existence of a blood flow improving effect.

[Comparative Example 1] Comparison of blood flow improvement effect Here, in order to compare the blood flow improvement effect of the composition for improving blood circulation of the present invention, the composition A for improving blood circulation and other comparative foods were ingested by rats. The blood flow velocity (μL / sec) after 4 hours was compared.

  A composition for improving blood circulation of the present invention and a comparative food are administered to Wistar rats (n = 5) at 50 mg / kg using an oral sonde, respectively, and a vacuum blood collection tube (manufactured by Terumo Corporation: heparin sodium treatment) ) Was used to collect blood. The obtained blood (test blood) was immediately used for measurement of blood flow velocity. For the control of the intake test, blood was also collected from the group of rats ingested with water, and the measurement was performed in the same manner as in Test Example 1. The measurement results of blood flow velocity are shown in Table 5.

  Compared with Control, there was a tendency for blood flow velocity to be improved by ingesting other foods that could improve blood flow. However, the composition A for improving blood circulation of the present invention, and further, It was confirmed that the blood flow velocity was remarkably increased in ingestion.

[Test Example 5] Confirmation of blood flow improvement effect 5
In order to confirm the effect of improving blood flow when the mixing ratio of elaeocarpsin, keblagic acid, geraniin and corilagin was changed as shown in Table 6, the mixing ratio of elaeocarpsin, keblagic acid, geraniin and corilagin was included in Table 6. To prepare compositions I to O for improving blood circulation. As in the test of Test Example 1, the final concentration was 0.1 μg / mL, and the change in blood flow rate (μL / sec) was investigated. The results are shown in Table 7.

  In the test group to which only LPS for inducing thrombus was added, the blood flow velocity was slower than that of the control. The blood flow velocity was improved in the test group in which the keblagic acid of the present invention was added to LPS. Furthermore, as a result of evaluating the compositions I to O for improving blood circulation, it was improved as compared to the effect of ketebraic acid alone, and significant improvements were observed in the compositions I, J, and K for improving blood circulation. For composition J, the blood flow velocity of control not loaded with LPS was improved to the same level.

[Test Example 6] Confirmation of platelet aggregation inhibitory activity 1
The platelet aggregation inhibitory activity of ellaeocalpsin, ketebraic acid, geraniin and corilagin was added to 200 μl of a healthy human platelet suspension using a platelet aggregometer (Aggregometer). Thereafter, 10 μl of ADP (1 mg / ml solution) was added as a substance causing aggregation, and the platelet aggregation rate after 5 minutes was measured.

  Separately, water (sample concentration 0 mg / ml) was added as a control, and the platelet aggregation rate was measured by the same method. From the measured platelet aggregation rate, the platelet aggregation inhibitory activity (%) relative to the control was calculated according to the following formula.

  Platelet aggregation inhibition activity (%) = (control platelet aggregation rate−platelet aggregation rate at the time of sample addition) / control platelet aggregation rate × 100

  Table 8 shows the results of measurement using samples prepared by diluting elaeocalpsin, keblagic acid, geraniin, and corilagin with distilled water to 0.125, 0.25, and 0.5 mg / ml, respectively. .

  From the results shown in Table 8 above, it was confirmed that in the platelet aggregation test, elaeocalpsin, keblagic acid, geraniin and corilagin showed high platelet aggregation inhibitory activity. It was also confirmed that the platelet aggregation inhibitory activity was increased by increasing the concentration of the composition for improving blood circulation.

[Test Example 7] Confirmation of platelet aggregation inhibitory activity 2
The platelet aggregation inhibitory activity of the compositions E to H for improving blood circulation of the present invention obtained in Example 4 was measured by the same method as in Test Example 6.

  Table 9 shows the results obtained by measuring the blood circulation improving compositions E to H of the present invention obtained in Example 4 as diluted with 0.25 mg / ml by diluting with distilled water. It was.

  From the results of Table 9 above, it was confirmed that the composition for improving blood circulation of the present invention showed high platelet aggregation inhibitory activity in the platelet aggregation test. It was also confirmed that the platelet aggregation inhibitory activity was increased by increasing the concentration of the composition for improving blood circulation.

[Test Example 8] Confirmation of platelet aggregation inhibitory activity 3
The platelet aggregation inhibitory activity of the compositions E to H for improving blood circulation of the present invention obtained in Example 4 was determined using a whole blood platelet aggregation ability measuring apparatus (WBA-Neo: manufactured by ASK Corporation). After adding 10 μl of sample to 200 μl of blood, 10 μl of ristocetine sulfate (American biochemical: 100 mg / vial) adjusted to a final concentration of 10 μM was added as a substance causing aggregation, and inhibition of platelet aggregation after 5 minutes Activity was measured.

  Separately, water (sample concentration 0 mg / ml) was added as a control, and platelet aggregation inhibitory activity was measured by the same method.

From the measured platelet aggregation rate, the platelet aggregation inhibitory activity (%) relative to the control was calculated according to the following formula.
Platelet aggregation inhibition activity (%) = (control platelet aggregation rate−platelet aggregation rate at the time of sample addition) / control platelet aggregation rate × 100

  As samples, the blood circulation improving compositions E to H of the present invention obtained in Example 4 were diluted with distilled water and adjusted to 0.125, 0.25, and 0.5 mg / ml, respectively. The results are shown in Table 10.

  From the results of Table 10 above, it was confirmed that in the platelet aggregation test, the composition for improving blood circulation of the present invention exhibits a platelet aggregation inhibitory effect on inhibiting the formation of a cross-link between collagen and GpIb by vWF. It was also confirmed that the platelet aggregation inhibitory activity was increased by increasing the concentration of the composition for improving blood circulation.

[Test Example 9] Confirmation of platelet aggregation inhibitory activity 4
The platelet aggregation inhibitory activity of the compositions E to H for improving blood circulation of the present invention obtained in Example 4 was determined using a whole blood platelet aggregation ability measuring apparatus (WBA-Neo: manufactured by ASK Corporation). After adding 10 μl of sample to 200 μl of blood, 10 μl of thrombin (Wako Pure Chemical Industries, Ltd .: 100 mg / vial) adjusted to a final concentration of 5 μM was added as a substance causing aggregation. Platelet aggregation rate was measured.

  Separately, water (sample concentration 0 mg / ml) was added as a control, and the platelet aggregation rate was measured by the same method. From the measured platelet aggregation rate, the platelet aggregation inhibitory activity (%) relative to the control was calculated according to the following formula.

Platelet aggregation inhibition activity (%) = (control platelet aggregation rate−platelet aggregation rate at the time of sample addition) / control platelet aggregation rate × 100
As samples, the blood circulation improving compositions E to H of the present invention obtained in Example 4 were diluted with distilled water and adjusted to 0.125, 0.25, and 0.5 mg / ml, respectively. The results are shown in Table 11.

From the results shown in Table 11 above, it was confirmed that the blood circulation improving composition of the present invention has an effect of suppressing platelet aggregation induced by thrombin in the platelet aggregation test. It was also confirmed that the platelet aggregation inhibitory activity was increased by increasing the concentration of the composition for improving blood circulation.

[Test Example 10] Confirmation 1 of blood coagulation inhibitory effect
The blood coagulation-inhibiting activity of elaeocalpsin, keblagic acid, geraniin and corilagin was measured with a coagulometer using platelet poor plasma (Platelet Poor Plasma, PPP) separated from human blood.

  5 microliters of sample and 45 microliters of PPP are put in a reaction cuvette and reacted at 37 ° C. for 1 minute, and then 50 microliters of APTT reagent is placed and reacted at 37 ° C. for 2 minutes. Finally, 50 microliters of a 25 mM calcium chloride solution was added and allowed to clot, and the time until the plasma was clotted was measured and designated APTT.

  Table 12 shows the results of measurement using samples prepared by diluting elaeocalpsin, keblagic acid, geraniin, and corilagin with distilled water to 250, 125, and 62.5 μg / ml, respectively.

  From the results of Table 12 above, it was confirmed that the composition for improving blood circulation of the present invention exhibits high blood coagulation inhibitory activity. It was also confirmed that blood coagulation inhibitory activity was increased by increasing the concentration of the extract.

[Test Example 11] Confirmation 2 of blood coagulation inhibitory effect
The blood coagulation inhibitory activity of the compositions E to H for improving blood circulation of the present invention obtained in Example 4 was measured by the same method as in Test Example 10.

  Table 13 shows the results of measurement using the samples E to H for improving blood circulation of the present invention obtained in Example 4 diluted with distilled water and adjusted to 125 μg / ml.

  From the results of Table 13 above, it was confirmed that the composition for improving blood circulation of the present invention showed high blood coagulation inhibitory activity. It was also confirmed that blood coagulation inhibitory activity was increased by increasing the concentration of the extract.

[Test Example 12] Confirmation of blood coagulation inhibitory effect 3
Regarding the blood coagulation inhibitory activity of the blood circulation improving compositions E to H of the present invention obtained in Example 4, “APTT reagent 50 microliters and 25 mM calcium chloride solution 50 microliters of Test Example 10” were used as blood coagulation reagents. ”Was used instead of“ 100 microliters of PT reagent ”.

  That is, 5 microliters of sample and 45 microliters of PPP are put in a reaction cuvette and reacted at 37 ° C. for 3 minutes, and then 100 microliters of PT reagent is placed and coagulated at 37 ° C. to coagulate plasma. Was measured as PT.

  In order to confirm the relationship between the concentration of the composition E to H for improving blood circulation of the present invention and the blood coagulation inhibitory activity, the present application has a solid content concentration of 0 (control), 250, 125, 62.5 μg / ml. The inventive blood circulation improving composition was used to measure its activity. The results are shown in Table 14 below.

[Reference Example 1] Preparation of blood circulation improving composition-containing food (tablet confectionery) Blood circulation improving composition E obtained in Example 4, 0.5 g, lactose 30 g, DHA-containing powdered oil (Suncoat DY- 5; manufactured by Taiyo Kagaku Co., Ltd.) 12 g, sucrose fatty acid ester 4 g, and yoghurt flavor 4 g are mixed, and this mixture is pressure-molded using a rotary tableting machine to improve the blood circulation of the present invention with one tablet of 300 mg. Composition-containing food or drink (tablet confectionery) was obtained.

  Further, a blood circulation improving composition-containing food or drink (tablets) was obtained in the same manner except that the blood circulation improving compositions F to H were used instead of the blood circulation improving composition E. In addition, as a comparative example for this, food and drink (tablets) containing other components such as lactose were obtained by the same method, while not containing only the composition for improving blood circulation.

  And about these 5 types of tablet confectionery, as a result of having conducted the sensory test by five panelists, the difference in any of a color, an odor, and taste was not recognized. In addition, when these two types of tablet confectionery were stored at room temperature for a long time (1 month, 3 months, 6 months), no noticeable changes in color, odor and taste were observed, and none of them was preserved. It was excellent.

[Reference Example 2] Preparation of a beverage containing a composition for improving blood circulation Composition B for improving blood circulation obtained in Example 4, 0.5 g, 2.1 g of 1/5 concentrated grapefruit transparent fruit juice, 30 g of erythritol, citric acid Crystals 2.5 g, trisodium citrate 0.5 g, L-ascorbic acid 0.5 g, calcium lactate 1.93 g, CCP 0.15 g, and grapefruit flavor 1.0 were mixed and dissolved in water to make a total volume of 1000 mL. After filling it into a 100 mL bottle and sealing with a cap, it was sterilized by heating at 90 ° C. for 30 minutes to obtain a food / beverage product (beverage) containing the composition for improving blood circulation of the present invention. Further, a blood circulation improving composition-containing food or drink (beverage) was obtained in the same manner except that the blood circulation improving compositions F to H were used instead of the blood circulation improving composition E. Moreover, as a comparative example to this, although not containing only the composition for blood circulation improvement, the food-drinks (beverage) containing another component were obtained by the same method.

  And about these 5 types of drinks, as a result of having performed the sensory test by five panelists, the difference in any of a color, an odor, and taste was not recognized. In addition, when these two types of beverages were stored in a refrigerator for a long period (1 month, 3 months, 6 months), no noticeable changes in color, smell and taste were observed, and all of them were preserved. It was excellent.

[Reference Example 3] Preparation of composition containing beverage for improving blood circulation (vegetable juice mixed drink) Composition E for improving blood circulation obtained in Example 4, 0.05 g, guar gum degradation product (Sunfiber R; Taiyo Kagaku) 3 g) was added to, mixed and dissolved in 100 mL of a commercially available vegetable fruit juice mixed drink, to obtain a blood circulation improving composition-containing food or drink (vegetable fruit juice mixed drink) of the present invention. Furthermore, in place of the composition E for improving blood circulation, the composition-containing food and drink (vegetable juice mixed drink) for improving blood circulation was obtained in the same manner except that the compositions F to H for improving blood circulation were used. Moreover, the food / beverage products (vegetable juice mixed drink) which do not contain the composition for blood circulation improvement but contain a guar gum decomposition product as a comparative example with respect to this were obtained by the same method.

  And as a result of having conducted the sensory test by five panelists about these 5 types of vegetable juice mixed drinks, the difference in any of a color, an odor, and taste was not recognized. Moreover, when these five kinds of beverages were stored in a refrigerator for one month, no noticeable changes were observed in color, smell and taste, and all of them were excellent in storage stability.

[Reference Example 4] Preparation of cookie containing composition for improving blood circulation After putting 0.4 g of composition E for blood circulation obtained in Example 4 and 200 g of commercially available cake mix powder into a container, 35 g of butter was added. And mixed with a wooden cocoon. 25g of beaten egg was added to it and kneaded well until it became a smooth dough. The dough is taken out on a table on which the flour has been shaken, and the flour is further shaken and stretched to a thickness of 5 mm with a rolling pin, extracted with a round shape, and baked in an oven at 170 ° C. for 10 minutes, and about 5 g of this invention. Obtained a cookie containing a composition for improving blood circulation. Furthermore, a composition-containing cookie for improving blood circulation was obtained in the same manner except that the compositions F to H for improving blood circulation were used instead of the composition E for improving blood circulation.

Reference Example 5 Preparation of Yogurt Containing Composition for Improving Blood Circulation Composition E for blood circulation obtained in Example 4, 0.1 g, 95 g of commercially available skim milk (manufactured by Meiji Dairies, protein content 34%) And 35 g of commercially available unsalted butter (manufactured by Snow Brand Milk Products Co., Ltd.) was dissolved in 0.8 L of warm water, homogenized, and the total amount was adjusted to 1 L. Next, this was heat sterilized at 90 ° C. for 15 minutes, cooled, and inoculated with 3 g of commercially available lactic acid bacteria starter (manufactured by Hansen) (2 g of Streptococcus thermophilus and 1 g of Lactobacillus bulgaricus). Furthermore, after mixing this uniformly, dispensing and filling into a 100 mL container, sealing, fermenting at 37 ° C. for 20 hours, and then cooling to obtain the yogurt containing the composition for improving blood circulation of the present invention. Obtained. Furthermore, a yogurt containing a composition for improving blood circulation was obtained in the same manner except that the compositions for improving blood circulation F to H were used instead of the composition E for improving blood circulation.

[Reference Example 6] Preparation of oral liquid food containing composition for improving blood circulation 50 g sodium caseinate (DMV), 42.5 g egg white enzyme degradation product (Taiyo Kagaku), 100 g dextrin (Matsuya Chemical) Dissolved in 1 L, the aqueous phase was prepared in a tank. Separately, 45 g of MCT (manufactured by Kao Corporation), 17.5 g of palm oil (manufactured by Fuji Oil Co., Ltd.), 35 g of safflower oil (manufactured by Taiyo Oil & Fats Co., Ltd.), 0.7 g of lecithin (manufactured by Taiyo Kagaku Co., Ltd.), defoaming 1 g of an agent (manufactured by Taiyo Chemical Co., Ltd.) was mixed and dissolved to prepare an oil phase. The oil phase was added to the aqueous phase in the tank, stirred and mixed, then heated to 70 ° C., and further homogenized with a homogenizer at a pressure of 14.7 MPa. Next, the mixture was sterilized at 90 ° C. for 10 minutes, then concentrated and spray-dried to prepare about 260 g of an intermediate product powder. 200 g of this intermediate product powder, 0.4 g of the blood circulation improving composition E obtained in Example 4, 159 g of dextrin (manufactured by Matsutani Chemical Co., Ltd.), 18 g of guar gum decomposition product (Sunfiber R; manufactured by Taiyo Chemical Co., Ltd.) A small amount of vitamin / mineral and powdered flavor were added and mixed uniformly to obtain about 380 g of an oral liquid food containing the composition E for improving blood circulation. Furthermore, an oral liquid food containing a composition for improving blood circulation was obtained in the same manner except that the compositions F to H for improving blood circulation were used instead of the composition E for improving blood circulation.

[Example 5] Preparation of tablets containing composition for improving blood circulation E, 1 g of blood circulation improving composition obtained in Example 4, 5 g of crystalline cellulose, 13.8 g of corn starch, 32.5 g of lactose, hydroxypropylcellulose 3.3 g was mixed and granulated. 1.0 g of magnesium stearate is added to the granulated product, mixed uniformly, and this mixture is pressure-molded with a rotary tableting machine, whereby a tablet containing 130 mg of the composition for improving blood circulation according to the invention of the present invention is obtained. Got. Further, a composition-containing tablet for improving blood circulation was obtained in the same manner except that the compositions for improving blood circulation F to H were used instead of the composition E for improving blood circulation.

[Example 6] Preparation of drink containing composition for improving blood circulation Into the blood circulation improving composition E obtained in Example 4, 5.5 g, glucose 528 g, fructose 85.4 g, powdered citric acid 15.8 g 11.2 g of sodium citrate, 1.3 g of calcium lactate, 1.3 g of magnesium chloride, 13.2 g of powdered natural flavor, vitamin C were added, and water was added to make 11 liters. This liquid was filled in a dry heat sterilized 110 ml brown bottle, sealed with an aluminum cap, and then sterilized at 120 ° C. for 30 minutes to obtain 100 drinks. Furthermore, a composition-containing drink for improving blood circulation was obtained in the same manner except that the compositions F to H for improving blood circulation were used instead of the composition E for improving blood circulation.

Example 7 Preparation of Capsules Containing Composition for Improving Blood Circulation After adding 50 g of copper chlorophyllin sodium to 50 g of the composition E for improving blood circulation obtained in Example 4 and heat sterilizing it, the Japanese Pharmacy Capsules (# 1) were filled with 0.4 g per capsule to obtain 100 capsules. Furthermore, the composition-containing capsule for improving blood circulation was obtained in the same manner except that the blood circulation improving compositions F to H were used instead of the blood circulation improving composition E.

[Reference Example 7] Preparation of feed for breeding swine containing a composition for improving blood circulation 44.5 parts by weight of corn and 28 parts of milo for 0.5 parts by weight of composition F for improving blood circulation obtained in Example 4 0.0 parts by weight, soybean oil residue 11.0 parts, bran 6.0 parts by weight, fish meal 5.0 parts by weight, animal fats and oils 2.0 parts by weight, vitamins and minerals 3.0 parts by weight Then, 20 kg of pig breeding feed was prepared. Furthermore, a composition for improving blood circulation containing pig breeding feed was obtained in the same manner except that the blood circulation improving compositions F to H were used instead of the blood circulation improving composition E.

Examples of the present invention and the target product are as follows.
(1) A composition for improving blood circulation, comprising ellagitannin as an active ingredient.
(2) The composition for improving blood circulation according to (1) above, wherein ellagitannin as an active ingredient is extracted from a natural plant.
(3) The composition for improving blood circulation according to (1) above, wherein ellagitannin as an active ingredient is extracted from Amler.
(4) The composition for improving blood circulation as described in (1) above, wherein ellagitannin, which is an active ingredient, is extracted from Genokosho.
(5) The composition for improving blood circulation as described in (1) above, wherein ellagitannin as an active ingredient is extracted from strawberry tea.
(6) The composition for improving blood circulation according to (1) above, wherein ellagitannin as an active ingredient is extracted from momotana.
(7) The composition for improving blood circulation as described in (1) above, wherein ellagitannin, which is an active ingredient, is extracted from Akamega wrinkles.
(8) The composition for improving blood circulation as described in (1) above, wherein ellagitannin, which is an active ingredient, is extracted from Megurinoki.
(9) The composition for improving blood circulation as described in (1) above, wherein ellagitannin, which is an active ingredient, is extracted from a wallworm.
(10) The composition for improving blood circulation according to (1) above, wherein ellagitannin as an active ingredient is extracted from Chancapiedra.
(11) The composition for improving blood circulation according to the above (1), wherein ellagitannin as an active ingredient is extracted from sunshuyu.
(12) The composition for improving blood circulation according to the above (1), wherein ellagitannin as an active ingredient is extracted from a pentaploid.
(13) The composition for improving blood circulation according to (1) above, wherein ellagitannin as an active ingredient is extracted from banaba.
(14) The composition for improving blood circulation according to the above (1), which contains at least one selected from the group consisting of ellaeocarpsin, keblagic acid, geraniin and corilagin as an active ingredient as ellagitannin. .
(15) The composition for improving blood circulation as described in (1) above, wherein the active ingredients elaeocalpsin, keblagic acid, geraniin and corilagin are extracted from natural plants.
(16) The composition for improving blood circulation as described in (1) above, wherein the active ingredients elaeocalpsin, keblagic acid, geraniin and corilagin are extracted from Amler.
(17) The composition for improving blood circulation according to the above (1), wherein geraniin and corilagin as active ingredients are extracted from Genokosho.
(18) The composition for improving blood circulation according to the above (1), wherein the active ingredients ketebraic acid and corilagin are extracted from momotana.
(19) The composition for improving blood circulation according to the above (1), wherein geraniin, which is an active ingredient, is extracted from red mulberry wrinkles.
(20) The composition for improving blood circulation as described in (1) above, wherein the active ingredients elaeocarpsin and geraniin are extracted from Megurinoki.
(21) The composition for improving blood circulation according to the above (1), wherein corilagin as an active ingredient is extracted from a wallworm.
(22) A fraction obtained by purifying a product obtained by treating and decomposing a plant with at least one enzyme selected from the group consisting of pectinase, protease, tannase and cellulase in (2) to (21) As a composition for improving blood circulation.
(23) In the above (1) to (22), the content ratio of the mixture comprising elaeocarpsin, keblagic acid, geraniin and corilagin as active ingredients is 5% by weight, and elaeocalpsin is 5 to 80%, keblagic acid. 5 to 80%, geraniin 5 to 80%, and corilagin 5 to 80%, respectively.
(24) In the above (1) to (22), the content ratio of the mixture comprising elaeocalpsin, keblagic acid, geraniin and corilagin, which are active ingredients, is 10% by weight and 10-40% elaeocarpsin, 10 to 40%, geraniin 10 to 40% and corilagin 10 to 40%, respectively.
(25) A food or drink comprising the composition for improving blood circulation according to any one of (1) to (24) above.
(26) A feed comprising the composition for improving blood circulation according to any one of (1) to (24) above.
(27) A quasi-drug containing the composition for improving blood circulation according to any one of (1) to (24) above.
(28) A pharmaceutical comprising the composition for improving blood circulation according to any one of (1) to (24) above.
(29) A blood circulation improving method for improving blood circulation using the composition for improving blood circulation according to any one of (1) to (24) above.
(30) A blood circulation improving method for improving blood circulation in vivo using the blood circulation improving composition according to any one of (1) to (24).
(31) A blood circulation improving method in which a living organism is ingested with the composition for improving blood circulation according to any one of (1) to (24), and blood circulation is improved in the living body.
(32) The method for improving blood circulation according to the above (31), wherein the organism is an organism excluding humans.
(33) The composition of (1) to (32) wherein the blood circulation improvement is blood flow improvement (34) The food and drink of (1) to (32) wherein the blood circulation improvement is blood flow improvement (35) Blood circulation improvement (1) to (32) feed (36) Blood circulation improvement is blood flow improvement (1) to (32) Quasi-drug (37) Blood circulation improvement is blood flow improvement A certain pharmaceutical (1) to (32).
(38) The composition of (1) to (32) wherein blood circulation improvement is inhibition of platelet aggregation (39) The food and drink of (1) to (32) wherein improvement of blood circulation is inhibition of platelet aggregation (40) Improvement of blood circulation (1) to (32) feed (41) Blood circulation improvement is platelet aggregation inhibition (1) to (32) Quasi-drug (42) Blood circulation improvement is platelet aggregation inhibition Certain (1) to (32) pharmaceuticals (43) The composition of (1) to (32) wherein blood circulation improvement is suppression of blood coagulation (44) The blood circulation improvement is suppression of blood coagulation (1) to (32 (45) Feed of (1) to (32) whose blood circulation improvement is suppression of blood coagulation (46) Quasi-drug of (1) to (32) where improvement of blood circulation is suppression of blood coagulation 47) The pharmaceutical product according to (1) to (32), wherein blood circulation improvement is suppression of blood coagulation.

Claims (1)

  A pharmaceutical composition for improving blood circulation, comprising any one selected from the group consisting of elaeocarpusin, chebulagic acid and geraniin.