JP2011162444A - Composition for suppressing vascular disease marker - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition for suppressing a vascular disease marker, which can be widely used as food and drink, feed, quasi drugs, pharmaceutical products, etc., because it is highly safe, highly practical and is excellent in action of protecting vascular endothelial cells. <P>SOLUTION: The composition for suppressing a vascular disease marker comprises at least one chosen from the group consisting of Indian gooseberry fruit, Indian gooseberry juice, Indian gooseberry fruit extract and Indian gooseberry juice extract as an active ingredient. Indian gooseberry refers to a plant native to India with a scientific name of Emblica officinale or Phyllanthus emblica. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a composition for adjusting the amount of a marker protein that changes quantitatively with vascular endothelial injury, and to foods, drinks, feeds, quasi drugs, and pharmaceuticals containing the same.

In recent years, according to statistics by Japanese cause of death, the total number of deaths of patients with cardiovascular and cerebrovascular disorders, which are atherosclerotic thromboembolism, exceeds the number of malignant tumor patients with the first cause of death. . It is difficult to maintain QOL of thrombotic patients who have once developed, and this has contributed to the deterioration of the medical economy. To prevent this, it is most important to prevent and prevent the onset of thrombosis.
A thrombus is a blood clot that forms in a blood vessel. Thrombus is known to progress from platelet thrombus to fibrin thrombus. Platelet thrombus is caused by adhesion and aggregation of platelets activated by various causes such as plaque rupture to the intima. Fibrin thrombus is caused by the involvement of various coagulation factors such as fibrinogen. When the body is normal, the fibrinolytic enzyme dissolves the fibrin that is the source of the thrombus, thereby preventing the thrombus. However, when the fibrinolytic enzyme is insufficient, fibrin cannot be dissolved and a thrombus is formed.

The formed thrombus is deposited in the blood vessel to reduce the cross-sectional area of the blood vessel and inhibit blood circulation. Then, blood cannot normally supply nutrients and oxygen to cells and tissues, and blood cannot discharge waste products from cells and tissues. Therefore, problems such as accumulation of waste products occur.
Symptoms caused by blood clots in blood vessels are called thrombosis in a broad sense (hereinafter simply referred to as thrombosis in a broad sense when simply described as “thrombosis”). In addition, pathological conditions caused by blood clots can be divided into thrombosis in a narrow sense and embolism. In the narrow sense, thrombosis refers to a pathological condition caused by partial or complete blockage of blood flow at a site where a thrombus is formed. Embolism refers to a pathological condition that occurs when a blood clot is peeled off from a site where it is formed and moved by blood flow, and the blood flow is partially or completely occluded at other sites.

Such thrombosis induces various diseases depending on the site of the blood vessel in which the thrombus has occurred. In particular, when a thrombus occurs in a cerebral blood vessel or a cardiovascular blood vessel, serious symptoms such as stroke, cerebral hemorrhage, cerebral infarction, heart failure, myocardial infarction, heart palsy and the like are brought about. In this case, it may cause involuntary half-life and even death.
Serious thrombi that cause diseases such as heart disease and cerebrovascular disease differ from the fibrin thrombus formed under the bloodstream congestive zone in terms of mechanism, and in the presence of a relatively fast and abundant blood flow such as an artery. It is thought that it is formed by. In the presence of blood flow, clotting factors are diluted by blood even when activated, and thus do not lead to thrombus formation. However, platelets, a component that increases the local concentration by adhering and aggregating to the damaged vessel wall, play a more important role in the formation of thrombus.

When vascular endothelial cells are damaged and detached, collagen in the vascular endothelial subcellular tissue is exposed. Then, von Willebrand factor (von Willebrand factor: vWF: Factor VII) synthesized in vascular endothelial cells acts to form (adhere) a bridge between collagen and the vWF receptor (GpIb). In addition, platelets are activated by agonists such as thrombin and bind to other platelets via fibrinogen by the fibrinogen receptor (GpIIb-IIIa). As a result, platelet aggregation is caused and a platelet thrombus is formed. Therefore, the formation of a cross-link between collagen and GpIb by vWF or whether fibrinogen and other serum proteins can suppress the binding of GpIIb-IIIa is one important requirement for preventing thrombus formation.
vWF is a plasma glycoprotein that plays an important role in the formation of blood clots in damaged blood vessel walls and has two important hemostatic functions. One adheres the platelets under the damaged vascular endothelial cells as a ligand on the platelets, causing the first step of platelet thrombus. The other binds to blood coagulation factor VIII, stabilizes factor 8 as a carrier protein, and has a coagulation thrombus-inducing action on the platelet thrombus site. In addition, vWF is examined as an index of vascular endothelial injury and dysfunction, and it has been shown that an increase in antigen amount is increased in diseases such as cerebral infarction and myocardial infarction, and is a risk factor for cardiovascular events. ing.

In recent years, a glycoprotein called thrombomodulin (TM) having a strong affinity for thrombin has been discovered as an antithrombotic factor expressed on the membrane surface of vascular endothelial cells. TM not only functions antithrombotic, but also inhibits fibrinolysis and acts to stabilize fibrin, and the physiological role of TM is important to regulate both blood coagulation and fibrinolysis It is being positioned as an important factor. In addition, since it is secreted into blood due to endothelial cell damage, it has become a dysfunctional marker for endothelial cells.
Currently, in order to solve thrombosis, research and development of antithrombotic agents and thrombus formation preventives that suppress the formation of thrombus and research and development of thrombolytic agents that dissolve the generated thrombus are mainly conducted. Yes.

As an agent for preventing platelet aggregation and thrombus formation, aspirin, ticlopidine, hirudin (thrombin inhibitor), thromboxane A2 synthase inhibitor and the like have been commercialized.
Thrombin causes platelet aggregation almost independently of other pathways. However, if platelets have not been previously activated by other mechanisms, there will be no substantially effective amount of thrombin. Hirudin is a very effective antithrombotic agent. However, thrombin inhibitors function as both antiplatelet and anticoagulants and can still cause excessive bleeding.

Aspirin and the like are widely used as antiplatelet therapeutic agents for preventing diseases such as myocardial infarction. However, aspirin is ineffective against platelet aggregation induced by ADP (adenosine diphosphate) and causes side effects such as gastrointestinal disorders. Therefore, in the fields of foods, quasi drugs, pharmaceuticals, etc., there is a demand for antiplatelet agglutination therapy drugs that are highly safe, inexpensive, and highly practical. Under such circumstances, recently, research on ingredients having a function of preventing diseases, improving constitution or activating the body through diet rather than treatment with pharmaceuticals has been attracting attention. And the component which can satisfy | fill such conditions probably exists in the natural product (for example, natural plant) which man used in the conventional diet.
Conventionally, components derived from natural products that can improve thrombosis include, for example, onion skin (for example, see Patent Document 1), kiwifruit extract (for example, see Patent Document 2), nattokinase (for example, Patent Document 3). Etc.) are known. In addition, other components such as polyunsaturated fatty acids and glucosamine are also known.

JP 2002-171934 A (2nd page) JP 2003-171294 A (pages 2-5) JP 2004-65047 A (page 3)

Onion thin skin, nattokinase, polyunsaturated fatty acid, and glucosamine have problems in terms of flavor and properties, and have a drawback that they cannot be widely applied to foods and the like, and thus have problems from the viewpoint of practicality. Nattokinase also has vitamin K that contributes to the production of coagulation factors, although it has a thrombolytic effect. In addition, kiwifruit extract has a problem from the viewpoint of practicality because of its weak activity in the neutral range.
The present invention has been made in view of the above-mentioned problems, and its purpose is that it has excellent safety and practicality in addition to having an excellent protective effect on vascular endothelial cells. An object of the present invention is to provide a composition for suppressing a vascular disorder marker that can be widely used in products, pharmaceuticals 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 vascular disorder marker-suppressing composition.

  Therefore, the inventors of the present invention have conducted diversified studies and studies for the purpose of searching for anticoagulant components from various natural plants. As a result, the quantitative change of the marker protein in the fruit and juice of a plant called “Amra” is reduced. It has been newly found that there is an action to do. Accordingly, the inventors of the present application have further developed this new knowledge and completed the following invention.

That is, the invention described in claim 1 is characterized by containing as an active ingredient at least one selected from the group consisting of Amla fruit, Amla fruit juice, Amla fruit extract and Amla fruit extract. The gist is to reduce the quantitative change of the vascular disorder marker. This composition exhibits a high protective effect on vascular endothelial cells and can prevent thrombus formation on the damaged blood vessel wall. 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. Amla has a sour taste, but unlike ingredients derived from onions, natto, etc., there are few difficulties with respect to flavor, and there are also few difficulties with respect to properties. Therefore, the composition is highly practical and can be widely used in foods and drinks, feeds, quasi drugs, pharmaceuticals, and the like.
The gist of the invention described in claim 2 is that, in claim 1, the extract is obtained by extracting at least one selected from the group consisting of Amla fruit and Amla fruit juice with a non-organic solvent. To do.
The gist of the invention described in claim 3 is that, in claim 1 or 2, a fraction obtained by using an organic solvent of the extract is contained as the active ingredient.
Invention of Claim 4 contains the fraction obtained by refine | purifying what decomposed | disassembled and processed the said extract with the enzyme in any one of Claim 1 thru | or 3 as said active ingredient This is the gist.
The gist of the invention described in claim 5 is that, in claim 4, the enzyme is a hydrolase.
The gist of the invention described in claim 6 is a food or drink comprising the vascular disorder marker suppressing composition according to any one of claims 1 to 5.
The gist of the invention described in claim 7 is a feed comprising the composition for suppressing a vascular disorder marker according to any one of claims 1 to 5.
The gist of the invention described in claim 8 is a quasi-drug containing the composition for suppressing a vascular disorder marker described in any one of claims 1 to 5.
The gist of the invention described in claim 9 is a pharmaceutical comprising the composition for suppressing a vascular disorder marker according to any one of claims 1 to 5.

Therefore, according to the invention described in claims 1 to 5, in addition to excellent protective action of vascular endothelial cells, it is widely used for food and drink, feed, quasi-drugs and pharmaceuticals because of its high safety and practicality. A vasopathic marker suppression composition that can be used can be provided.
Moreover, according to invention of Claim 6 thru | or 9, the food / beverage products, feed, quasi-drug, and pharmaceutical containing said outstanding vascular disorder marker suppression composition can be provided, respectively. For this reason, it becomes possible to suppress the generation of blood clots by protecting the vascular endothelial cells and prevent cardiovascular diseases such as stroke, cerebral hemorrhage, cerebral infarction, heart failure, myocardial infarction, heart palsy and the like.

The graph which shows the result of the vWF expression suppression effect in LPS stimulation HUVEC. The graph which shows the result of the vWF expression suppression effect in LPS stimulation HUVEC. The graph which shows the result of the vWF expression suppression effect in LPS stimulation HUVEC. The graph which shows the result of the vWF expression suppression effect in LPS stimulation HUVEC. The graph which shows the result of the vWF expression suppression effect in LPS stimulation HUVEC. The graph which shows the result of the vWF expression suppression effect in LPS stimulation HUVEC. The graph which shows the result of the vWF expression suppression effect in LPS stimulation HUVEC. The graph which shows the result of the vWF expression suppression effect in LPS stimulation HUVEC. The graph which shows the result of LDL cholesterol of a vascular disorder marker suppression composition administration. The graph which shows the inhibitory effect of TM of vascular disorder marker suppression composition A administration. The graph which shows the inhibitory effect of vWF of the vascular disorder marker suppression composition A administration.

Hereinafter, the vascular disorder marker suppression composition of one Embodiment which actualized this invention, and the food / beverage, feed, quasi-drug, and pharmaceutical which contain it are demonstrated in detail.
“Amula” used in the composition for suppressing a vascular injury marker of the present invention is a plant having the scientific name of Emblica officinalis or Philanthus embrica. Amla is a deciduous sub-tree that belongs to the Euphorbiaceae family, and is distributed from India to the Malaysian region and southern China, and is considered to be the country of origin. In addition, Amla has a unique name depending on each region or language, for example, citrus, oil sweets, Satsuma mushrooms, Emblic Mirobaran, Armaraki, Melaka tree, Malacca tree, Indian gooseberry, Aronra, Amira. , Amiraki, Amira Cattra, Nerikai, Neruri, Tasha, Kayuraka, Kemuraka, Nakhon Pong and others.
In the traditional Indian medicine “Ayurveda”, Amla is listed as one of the best results for all diseases. However, there has never been a specific report regarding the fact that Amla has an inhibitory effect on vascular disorder markers, and the present inventor has newly discovered this time after earnest research.

  Although it does not specifically limit as a site | part of Amla used for a vascular disorder marker suppression composition, A fruit is used preferably. The form of Amla fruit is not particularly limited, and any of immature fruit, fully ripe fruit, dried fruit and the like may be used. The use of fruit juice obtained by squeezing the fruit is also preferable. The form of the fruit juice is not particularly limited, and may be either liquid or powder. The merit of using fruit juice is that it can be used as it is because the content of the water-insoluble component is small, and the step of removing the component can be omitted.

  When using a product containing a water-insoluble component, such as fresh fruit or dried fruit, it is preferable to remove the water-insoluble component by extraction in order to enhance the vascular disorder marker inhibitory action.

  When using fresh fruits, after removing the seeds in advance, extraction is performed after adding water as necessary. In addition, in order to improve extraction efficiency, it is preferable to use what was crushed and homogenized with a mixer etc. as an extraction raw material. The same can be said basically for the case of using dried fruits, but in order to increase the extraction efficiency, it is preferable to grind the particles so as to have a particle size of 40 mesh or less. Fruit juice is also preferably used as an extraction raw material.

  The solvent and temperature conditions used for extraction are not particularly limited, and can be arbitrarily selected and set. As the extraction solvent, a non-organic solvent such as water, a base, or an acid, or an organic solvent such as a hydrophilic solvent or acetone can be selected. As the hydrophilic solvent, at least one selected from the group of lower alcohols consisting of methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol and butyl alcohol is preferable from the viewpoint of operability and extraction efficiency. However, extraction with a non-organic solvent is preferable rather than extraction with an organic solvent, and it is particularly preferable to select one of water, a base and an acid.

  When an acid or base is used as the extraction solvent, it is preferable to neutralize the extract. The salt produced by the neutralization reaction can be removed by a known method such as dialysis or gel filtration. However, when water is used as the extraction solvent, the neutralization reaction as described above is not necessary, and it is not necessary to remove the generated salt. Therefore, it is most preferable to use water from the viewpoint of reducing man-hours and cost.

  The acid used at this time is not particularly limited, and most acids can be used. However, from the viewpoint of easy availability and operability, the use of hydrochloric acid or sulfuric acid, or the combined use of hydrochloric acid and sulfuric acid is preferred.

  In addition, the base is not particularly limited, and most bases can be used. However, the use of sodium hydroxide or potassium hydroxide or the combined use of sodium hydroxide and potassium hydroxide is preferred from the viewpoint of availability and operability.

  The concentration of the acid or base used for the extraction is not particularly limited before or after the extract is treated with the enzyme. Although it varies depending on the strength of the acid or base, from the viewpoint of operability and extraction efficiency, it is preferable to use 0.01 to 0.5 molar acid or base.

  In the above extraction, 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 protective action on vascular endothelial cells. 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 often 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. In addition, you may perform an enzyme process with respect to an amla fruit or an amla fruit juice.

  Further, in the above extraction, it is preferable to repeat the extraction step once or more for the extraction residue. According to this method, the extraction efficiency can be improved. The solvent used for extraction in this case may be the same or different.

  The above extract can be used as it is, but it is more preferable to remove the insoluble substances and the solvent by performing treatments such as filtration, centrifugation and fractional distillation. By performing such treatment, the effect of protecting the vascular endothelium is enhanced, and the application range is widened.

  After removing the insoluble substances and the solvent, the fruit juice or the extract is directly or concentrated and then distributed using an organic solvent to obtain each solvent-soluble fraction. These solvent-soluble fractions are preferable because the effect of protecting the vascular endothelium is further increased. Examples of the organic solvent include lower alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, and butyl alcohol, ethyl acetate, butyl acetate, diethyl ether, methyl ether, methyl isobutyl ketone, hexane, acetone, and chloroform. Can be used. Further, in order to increase the purity of the soluble fraction, partitioning with other hydrophobic solvents can be combined, but in this case, the use of ethyl alcohol is preferred. The concentration of these solvents is not particularly limited, but from the viewpoint of yield and effect, the final concentration is preferably 20% to 80% (v / v), and 20% to 60% (v / v). Further preferred.

  In order to further increase the purity, for example, purification by chromatography or column using a hydrophobic resin based on phenol, styrene, acrylic acid, epoxyamine, pyridine, methacryl or the like may be performed. . In that case, as an eluent after resin adsorption, for example, lower alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, butyl alcohol, and acetone can be used alone or as an aqueous solution.

The extract and fraction can be used as they are, but if necessary, they can be used after being dried and powdered by means such as spray drying or freeze drying.
In the present invention, “suppression of vascular injury marker” refers to suppression of expression of von Willebrand factor (von Willebrand factor: vWF) or thrombomodulin (TM) (in other words, protection of vascular endothelial cells). Say. Regarding the protective action of vascular endothelial cells, for example, vascular endothelial cells in the Amla-added group and Amla-free group were stimulated with lipopolysaccharide (hereinafter referred to as LPS) (1 μg / mL) to form thrombus formation on the damaged vascular wall. This can be confirmed by measuring the expression of vWF, which plays an important role in the process. Incidentally, the present inventor has newly found that Amla has a protective effect on vascular endothelial cells because the measured value is lower in the Amla-added group than in the Amla-free group.

The composition for suppressing a vascular disorder marker 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 suppressing a vascular disorder marker of the present invention as a food or drink should be adjusted depending on the disease state, the body weight, age, constitution, physical condition, etc. of the sick person. The inhibitory composition can be appropriately set in the range of 0.05 to 20 g, preferably 0.1 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.

In this invention, when processing into a vascular disorder marker suppression 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, tryptophan, minerals such as calcium, magnesium, iron, zinc, copper, and, for example, α-linolenic acid, EPA, DHA, evening primrose oil, octacosanol, casein phosphopeptide (CPP) , Casein calcium peptide (CCP), water-soluble dietary fiber, insoluble dietary fiber, substances that contribute to human health such as oligosaccharides, and other useful substances approved as foods and food additives The above can be used.

  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. It is obtained by mixing with the inhibitor 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 vascular disorder marker suppressing composition and diluent. It may be.

  Injections suitable for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, emulsions and the like. Examples of the aqueous solution and suspension diluent include distilled water for injection and physiological saline. Examples of diluents for water-insoluble solutions and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethyl alcohol, polysorbate 80, and the like. The injection may further contain adjuvants such as preservatives, wetting agents, emulsifiers, dispersants, stabilizers (for example, lactose), and solubilizing agents (for example, glutamic acid and aspartic acid). These are sterilized, for example, by filtration through a bacteria storage filter, blending with a bactericide or irradiation. These can also be used by producing a sterile solid composition and dissolving it in sterile water or a sterile solvent for injection before use.

  The dose of the vascular disorder marker-suppressing composition of the present invention as a pharmaceutical is appropriately determined according to each case in consideration of the administration route, disease symptoms, age of the administration subject, sex, etc. Amla extract per adult is about 40 mg / day to 3 g / day, preferably 100 mg / day to 500 mg / 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 1 of Vascular Disorder Marker Inhibitory Composition
The Amura 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. 2 L of distilled water 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 the vascular disorder marker inhibitor composition A of the present invention. It was. The yield was 43.8%.

Test Example 1 Confirmation of protective action of vascular endothelial cells 1
In this test, the activity of the vascular disorder marker inhibiting composition A was confirmed as follows. First, HUVEC which is a vascular endothelial cell was seed | inoculated to 24well plate, and the cell was fully cultured. The cultured cells were treated with angiogenic marker inhibitor composition A and LPS (1 μg / mL) diluted to a predetermined concentration (3, 10, 30, 100 μg / mL) for 4 hours. After treatment, the activity of vWF, which plays an important role in thrombus formation on the damaged vessel wall expressed on HUVEC, was quantified.

  Details of the experimental method regarding the effect of Amla on the expression of LPS-induced vWF using HUVEC are shown below.

1. After culturing until the cells become confluent, the culture solution is removed and washed with PBS (−). After washing, the angiopathy marker inhibitor composition A and LPS (1 μg / mL) diluted to 4 different concentrations were mixed with the culture solution and added to each well (culture reaction). Moreover, the section which added the mixture of distilled water and a culture solution to each well as control is provided.
2. Four hours after the addition, the culture solution was collected, treated with an ELISA plate on which an anti-vWF polyclonal antibody was immobilized, for 2 hours, and then added with an anti-vWF HRP antibody and allowed to react for 1 hour.
3. Further, the mixture was mixed with a substrate (3,3 ′, 5,5′-tetramethylbenzidine borate) and then measured with a spectrophotometer (measurement 450 nm).
The activity of vWF is calculated as a percentage (%) when the measured value of non-stimulated cells is 100%. The result is shown in the graph of FIG.

  As a result, it was confirmed that the composition for inhibiting vascular injury marker of the present invention suppresses LPS-induced expression of vWF in a concentration-dependent manner.

Example 2 Preparation 2 of Vascular Disorder Marker Inhibitory Composition 2
The dried Amla 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. 2 L of distilled water was added to the residue, and extraction was repeated once more under the same conditions. The extracts were combined and concentrated under reduced pressure to 200 mL. Ethyl alcohol was added to this concentrated solution to prepare 1 L (final ethyl alcohol concentration 80%), and then allowed to stand at 4 ° C. for 24 hours, and then insoluble components were precipitated. The precipitate was removed by centrifugation, the supernatant was concentrated under reduced pressure, and redissolved in 1 L of water. Further, this was filtered to remove insoluble components, and then the filtrate was lyophilized to obtain 12.5 g (yield 15.6%) of the vascular disorder marker inhibiting composition B of the present invention.

  Similarly, the final concentration of ethyl alcohol was set to 20% to obtain 13.6 g (yield 17.0%) of the vascular disorder marker inhibiting composition C of the present invention. The final concentration of ethyl alcohol was set to 40% to obtain 20.8 g of composition D (yield 26.0%), and the final concentration was set to 60% to give composition E 21.2 g ( Yield 26.5%).

Example 3 Preparation 3 of Vascular Disorder Marker Inhibitory Composition 3
The dried Amla 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 the mixture was repeatedly extracted under the same conditions. The extracts were combined and then lyophilized to obtain about 37.0 g of a dried product. 1 L of ethyl alcohol was added to 35 g of the dried product, and the mixture was allowed to stand at 4 ° C. for 24 hours to precipitate insoluble components. The precipitate was removed by centrifugation, the supernatant was concentrated under reduced pressure, and redissolved in 1 L of water. Furthermore, after filtering this and removing an insoluble component, the filtrate was lyophilized | freeze-dried and the vascular disorder marker suppression harm composition F of this invention 3.5g was obtained.

Example 4 Preparation 4 of Vascular Disorder Marker Inhibitory Composition
The dried Amla 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, the supernatant was filtered, and the extract and the residue were separated. 2 L of distilled water was added to the residue, and extraction was repeated once again under the same conditions. The extracts were combined and concentrated under reduced pressure to 200 mL. Ethyl acetate was added to this concentrated solution to prepare 500 mL (final ethyl acetate concentration 60%), and after stirring well, left at 4 ° C. for 24 hours. Thereafter, the ethyl acetate layer was separated and concentrated under reduced pressure, and the filtrate was lyophilized to obtain 12.5 g of a vascular disorder marker inhibiting composition G of the present invention.

Example 5 Preparation 5 of Vascular Disorder Marker Inhibitory Composition
The dried Amla 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 further 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 was centrifuged (3000 rpm, 10 minutes), the supernatant was filtered, and the filtrate was spray-dried to obtain 45 g of a vascular disorder marker inhibiting composition H of the present invention.

Test Example 2 Confirmation of protective action of vascular endothelial cells 2
Vasopathic marker suppression composition B, C, D, E obtained in Example 2, Vasopathic marker suppression composition F obtained in Example 3, Vasopathic marker suppression obtained in Example 4 About the composition G and the vascular disorder marker suppression composition H obtained in Example 5, the vascular disorder marker suppression action was calculated by the same method as in Test Example 1. The results are shown in the graphs of FIGS.
As shown in the graphs of FIGS. 2 to 8, any of the vascular disorder marker inhibitor compositions B to F exhibited a high vascular disorder marker inhibitory action.

Example 6 Preparation of Food (Tablets) Containing Vascular Disorder Marker Suppressing Composition As an example of an amla-containing vascular disorder marker suppressing composition, the ingredients shown in Table 1 are mixed and then encapsulated in a capsule, and the vascular disorder marker suppressing composition A food product-containing food was prepared.

Comparative Example 1 Production of Control Tablet As an example of the control tablet, the raw materials shown in Table 1 were mixed and encapsulated in a capsule to produce a tablet.

Test Example 3 Confirmation of vascular endothelial cell protective action 3
In this test, the activity of the vascular disorder marker inhibiting composition A was confirmed as follows.
Selection of subjects Subjects who do not meet the following exclusion rules are males and females aged 20-75 who have high blood triglyceride levels (103-250 mg / ml) or low HDL cholesterol levels (less than 54 mg / ml). A total of 16 people were selected and randomly assigned to two groups, and it was confirmed that there was no difference in age, height, weight, BMI, triglyceride, HDL cholesterol, and HbA1c between the groups. The test was conducted in accordance with the main points of the Declaration of Helsinki, after sufficiently explaining the purpose and test method of the test to the subjects and obtaining written consent. Table 2 shows the subject background on the intake start date.

Examiners were selected in consideration of the following 11 items as exclusion rules.
1. Those who have a history of allergies or allergic diseases (including atopy) 2. Persons with symptoms of cerebrovascular disorder. 3. Patients with heart failure and history of myocardial infarction 4. Patients with atrial fibrillation and severe arrhythmia Person with severe renal dysfunction (serum creatinine 4.0 mg / dL or more)
6). 6. Person with severe liver dysfunction Diabetes patients who are difficult to control 8. Person with severe anemia (hemoglobin amount less than 7 g / dL) 10. Pregnant women, lactating women and those who may be pregnant 10. Those who are taking any internal medicine regularly or who are taking supplements that affect blood fluidity. Any other person who is judged inappropriate by the study doctor

  The test period was 4 weeks. The test meal or placebo was ingested 4 capsules (250 mg × 4 capsules) a day, 2 capsules each after breakfast and dinner. After a 5-week washout period, the test meal or placebo was again ingested 4 capsules (250 mg × 4 capsules) daily for 2 weeks after breakfast and dinner. The test period was terminated with the measurement 3 weeks after the end of ingestion. During the period from the start date of the test to the end date of the test, instruction was given to avoid overeating and overeating and to make no other changes in daily life.

  Every day from 2 weeks before the start of intake to 3 weeks after the end of intake, the intake time of the test food and placebo, the dosage and intake of drugs and supplements, the content and time of meal (drinking), and the sleeping time were entered in a diary.

  Blood collection was performed by nurses, avoiding eating and drinking (excluding water) after 10:00 the night before, avoiding smoking and intense exercise on the day of the examination, fasting until the end of the examination. The number of blood collections was performed twice before and 4 hours after intake of the test food and placebo on the test day (2 weeks after intake of the test food and 4 weeks after intake and 2 weeks after intake of the placebo and 4 weeks after intake).

  Red blood cell count (RBC), hematocrit value (Ht), hemoglobin level (Hb), average red blood cell pigment content (MCH), average red blood cell volume (MCV), average red blood cell color concentration (MCHC), white blood cell count (WBC) The platelet count (Plt) was measured.

  GOT (AST), GPT (ALT), γ-GTP, total protein, albumin, A / G ratio, neutral fat (TG), total cholesterol (T-Cho), HDL cholesterol (HDL-Cho) ), LDL cholesterol (LDL-Cho), ALP, uric acid, glucose, HbA1c, total bilirubin, urea nitrogen (BUN), creatinine, Na, Cl, K, Ca and P were measured.

Blood passage speed, PT, APTT, platelet aggregation ability, TM, vWF, 80H-dG, TBARS, and adiponectin were measured as vascular disorder index tests.
Statistical analysis is based on a normal distribution of total cholesterol, HDL cholesterol, LDL cholesterol and vascular disorder index test values, and a two-way analysis of variance (ANOVA) is performed to analyze the ingestion period and the alternation between the test food and placebo groups did. In comparison with pre-intake values, Dunnett's multiple comparison test was performed if normal distribution was followed, and Bonferroni's multiple comparison was performed after Wilcoxon signed rank sum test. Height, weight, BMI, hematology test value, blood biochemical test value, and urine quantitative test value are tested between the test food and placebo. If the normal distribution is followed, t-test is used. Otherwise, Wilcoxon is used. After the rank sum test, a Bonferroni multiple comparison was performed. For urine qualitative test results, Bonferroni's multiple comparison is performed after the χ ² test. The statistical software uses SPSS Ver13.0 manufactured by SPSS Co., Ltd., and the significance level is set to 5% or less by the two-sided test.

  The subject background is shown in Table 2 as the subject of the subject. One person who could not take the capsule 2 weeks after the intake of Phase I during the test period, the study could not be continued due to moving after observation after Phase I 1 A total of 2 people were dropped.

  In comparison between the groups, there was no significant difference between the test food group and the placebo group for any of the items. In the transition within the group, the hemoglobin value of the placebo group significantly decreased after 4 weeks of intake compared to 2 weeks before intake. In MCH and MCHC, both the placebo group and the test food group significantly decreased after 2 weeks of intake, 4 weeks after intake, and 3 weeks after completion of intake compared to 2 weeks before intake. However, all were minor fluctuations, and none deviated from the standard values.

  In this test, LDL cholesterol was significantly lower than the placebo group 2 weeks after ingestion of the test food group as shown in FIG. Moreover, although there was no significant difference, the test food group showed a low value after 2 weeks after ingestion compared to before intake. As shown in FIG. 10, the vascular disorder index is TM as compared to 2 weeks before ingestion in the test food group as shown in FIG. 10, 4 weeks after ingestion and 3 weeks after the end of ingestion as shown in FIG. 11, and 2 weeks after ingestion of vWF. And 3 weeks after the end of intake, there was a significant decrease.

  In the test food group of this study, TM and vWF showed a significant decrease on the measurement day after ingestion compared to before ingestion, so that the amla combination vascular injury marker inhibitory composition has a protective effect on vascular endothelial cells. It has been suggested.

Example 7 Preparation of food containing vasopathic marker suppression composition (tablet confectionery) Vascular dysfunction marker suppressing composition A, 5 g obtained in Example 1, 30 g lactose, DHA-containing powdered oil (Suncoat DY-5; 12 g of Taiyo Kagaku Co., Ltd.), 4 g of sucrose fatty acid ester, and 4 g of yogurt flavor were mixed. And this mixture was pressure-molded with the rotary type tableting machine, and 1 tablet obtained the food-drinks (tablet confectionery) containing the vascular disorder marker suppression composition of this invention of 300 mg. In addition, as a comparative example for this, food and drink (tablet confectionery) containing other components such as lactose was obtained by the same method by substituting dextrin for the vascular disorder marker inhibiting composition A.

  And as a result of performing a sensory test by these five kinds of tablet confectionery by five panelists, no significant difference was recognized in both color, smell and taste. In addition, when these two types of tablet confectionery were stored at room temperature for a long time (1 month, 3 months, 6 months), neither of them showed any particularly noticeable changes in color, smell or taste, and both were stored. It was excellent in nature.

Example 8 Preparation of Beverage Marker Inhibiting Composition-Containing Beverage Vascular Disorder Marker Inhibiting Composition B obtained in Example 2, 5 g, 1/5 concentrated grapefruit transparent fruit juice 2.1 g, erythritol 30 g, citrate crystal 2 0.5 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 vascular disorder marker suppressing composition of the present invention. Moreover, as a comparative example against this, food and drink (beverages) containing other components were obtained by the same method, while not containing only the vascular disorder marker suppressing composition B.

  And as a result of performing a sensory test by these five kinds of beverages with respect to these two kinds of beverages, no significant difference was observed in any of color, smell and taste. In addition, when these two types of beverages were stored in a refrigerator for a long time (1 month, 3 months, 6 months), no significant changes were observed in color, smell, and taste in either of them, and all of them were preserved. It was excellent.

Example 9 Preparation of Beverage Marker Suppressing Composition-Containing Beverage (Vegetable Juice Mixed Beverage) Vascular Disorder Marker Suppression Composition C, 0.2 g obtained in Example 2, Guar Gum Decomposition (Sun Fiber 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 food / beverage product (vegetable fruit juice mixed drink) containing the vascular disorder marker-suppressing composition of the present invention. Moreover, the food / beverage products (vegetable juice mixed drink) which do not contain the vascular disorder marker suppression composition C 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 performing the sensory test by these five kinds of vegetable juice mixed drinks by five panelists, no significant difference was recognized in any of color, smell and taste. In addition, when these two types of beverages were stored in a refrigerator for one month, no noticeable changes in color, smell, and taste were observed in either of them, and all were excellent in storage stability.

Example 10 Preparation of Cookie Impairment Marker Suppressing Composition-Containing Cookie After putting vascular disorder marker suppression composition D, 4 g obtained in Example 2 and 200 g of commercially available cake mix powder into a container, put 35 g of butter, I mixed it with a wooden lion. 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 further, the flour is shaken and stretched to a thickness of 5 mm with a rolling pin, extracted in a round shape, and baked in an oven at 170 ° C. for 10 minutes. Obtained a cookie-inhibiting marker-suppressing composition-containing cookie.

Example 11 Preparation of Yogurt Containing Vascular Disorder Marker Inhibitory Composition Composition Vascular Disorder Marker Inhibiting Composition H obtained in Example 5, 1 g, 95 g of commercially available skim milk (manufactured by Meiji Dairies Co., Ltd., 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, the mixture is uniformly mixed, dispensed and filled into a 100 mL container, sealed, fermented at 37 ° C. for 20 hours, and then cooled, so that the yogurt containing the vascular disorder marker suppressing composition of the present invention is contained. Got.

Example 12 Preparation of Oral Liquid Food Containing Vascular Disorder Marker Suppressing Composition 50 g sodium caseinate (DMV), 42.5 g egg white enzyme degradation product (Taiyo Kagaku), 100 g dextrin (Matsuya Chemical) 1 L water 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, vascular disorder marker inhibitor composition C, 4 g obtained in Example 2, 156 g of dextrin (manufactured by Matsutani Chemical Co., Ltd.), 18 g of guar gum degradation product (Sunfiber R; manufactured by Taiyo Kagaku Co., Ltd.), A small amount of vitamins / minerals and powdered fragrance were added and mixed uniformly to obtain about 380 g of an oral liquid food containing a vascular disorder marker suppressing composition.

Example 13 Preparation of Tablet Containing Vascular Disorder Marker Inhibiting Composition Vascular Disorder Marker Inhibiting Composition F, 10 g obtained in Example 3, 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 this granulated product and mixed uniformly, and this mixture is pressure-molded with a rotary tableting machine, so that each tablet contains the composition for inhibiting vascular disorder marker of the present invention of 130 mg. Tablets were obtained.

Example 14 Preparation of Tablet Comprising Vascular Disorder Marker Inhibiting Composition Vascular Disorder Marker Inhibiting Composition F, 10 g obtained in Example 3, 5 g of crystalline cellulose, 13.8 g of corn starch, 32.5 g of lactose, hydroxypropylcellulose 3.3 g was mixed and granulated. To this granulated product, 1.0 g of magnesium stearate is added, mixed uniformly, and this mixture is pressure-molded using a rotary tableting machine, whereby one tablet is 130 mg of the vascular disorder marker suppression composition of the present invention. A product-containing tablet was obtained.

Example 15 Preparation of drink containing vascular dysfunction marker inhibitory composition Into the vascular dysfunction marker inhibitory composition G obtained in Example 4, 55 g, glucose 528 g, fructose 85.4 g, powdered citric acid 15.8 g, citrus Sodium 11.2 g, calcium lactate 1.3 g, magnesium chloride 1.3 g, powdered natural flavoring 13.2 g, 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.

Example 16 Preparation of Capsules Containing Vascular Disorder Marker Inhibiting Composition Addition of 1 g of copper chlorophyllate sodium to 50 g of vasculopathy marker suppressing composition G obtained in Example 4 was followed by heat sterilization. The pharmacy capsule (# 1) was filled with 0.4 g per capsule to obtain 100 capsules.

  Example 17 Preparation of feed for breeding pigs containing a composition for inhibiting vascular disorder markers

  40.0 parts by weight of corn, 28.0 parts by weight of milo, 11.0 parts by weight of soybean meal, 6.0 parts by weight of bran with respect to 5 parts by weight of the composition for inhibiting vascular injury marker B obtained in Example 2 Part by weight, 5.0 parts by weight of fish meal, 2.0 parts by weight of animal fats and oils, and 3.0 parts by weight of vitamins and minerals were prepared to prepare 20 kg of pig breeding feed.

Examples of the present invention and the target product are as follows.
(1) A composition for suppressing a vascular disorder marker, comprising as an active ingredient at least one selected from the group consisting of Amla fruit, Amla fruit juice, Amla fruit extract and Amla fruit extract.
(2) In the above (1), the extract is at least one selected from the group consisting of water, base, acid and hydrophilic solvent, at least one raw material selected from the group consisting of Amla fruit and Amla fruit juice. A composition for suppressing a vascular disorder marker, characterized in that it is extracted by one.
(3) In the above (1), the extract is obtained by extracting at least one raw material selected from the group consisting of Amla fruit and Amla fruit juice with water. object.
(4) In the above (2), the hydrophilic solvent is at least one lower alcohol selected from the group consisting of methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol and butyl alcohol. Vascular disorder marker inhibitor composition.
(5) In said (1), while containing the fraction by the organic solvent of the said extract as said active ingredient, the said organic solvent is methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, butyl alcohol, A composition for suppressing a vascular disorder marker, which is at least one selected from the group consisting of ethyl acetate, butyl acetate, diethyl ether, methyl ether, methyl isobutyl ketone, hexane and chloroform.
(6) A composition for suppressing a vascular injury marker according to the above (1), comprising a fraction of the extract with ethyl alcohol as the active ingredient.
(7) A composition for suppressing a vascular injury marker according to (1), wherein the extract contains an ethyl alcohol precipitation fraction component as the active ingredient.
(8) In the above (1), a composition for inhibiting a vascular injury marker comprising the soluble fraction obtained by fractionating the extract with 20% to 80% ethyl alcohol as the active ingredient object.
(9) In the above (1), a composition for suppressing a vascular injury marker comprising the soluble fraction obtained by fractionating the extract with 20% to 60% ethyl alcohol as the active ingredient object.
(10) A composition for suppressing a vascular disorder marker according to the above (1), which contains, as the active ingredient, a product obtained by purifying the extract by chromatography or column using a hydrophobic resin.

(11) In (10) above, the hydrophobic resin is based on at least one resin selected from the group consisting of phenolic, styrene, acrylic acid, epoxyamine, pyridine and methacrylic. A composition for suppressing a vascular disorder marker, comprising:
(12) In the above (1), a fraction obtained by purifying a product obtained by treating and decomposing the extract with at least one enzyme selected from the group consisting of pectinase, protease, tannase and cellulase, It contains as said active ingredient, The vascular disorder marker suppression composition characterized by the above-mentioned.
(13) A composition for suppressing a vascular disorder marker, comprising Amla as an active ingredient.
(14) A composition for suppressing a vascular disorder marker, comprising an edible part of Amla as an active ingredient.
(15) A composition for suppressing a vascular disorder marker, comprising an amla-derived substance as an active ingredient.
(16) A food or drink comprising the composition for suppressing a vascular disorder marker according to any one of (1) to (15) above.
(17) A feed comprising the composition for suppressing a vascular disorder marker according to any one of (1) to (15) above.
(18) A quasi-drug containing the vascular disorder marker-suppressing composition according to any one of (1) to (15) above.
(19) A pharmaceutical comprising the vascular disorder marker-suppressing composition according to any one of (1) to (15) above.
(20) An vascular endothelial cell using a vascular injury marker suppressing composition containing, as an active ingredient, at least one selected from the group consisting of Amla fruit, Amla fruit juice, Amla fruit extract and Amla fruit extract Protection method.

(21) A method for protecting vascular endothelial cells using a vascular disorder marker-suppressing composition containing amla as an active ingredient.
(22) A method for protecting vascular endothelial cells using a composition for suppressing vascular injury marker comprising an edible portion of Amla as an active ingredient.
(23) A method for protecting vascular endothelial cells using a composition for inhibiting vascular injury marker containing an amla-derived substance as an active ingredient.
(24) A vascular endothelial cell using a vascular injury marker suppressing composition containing, as an active ingredient, at least one selected from the group consisting of Amla fruit, Amla fruit juice, Amla fruit extract and Amla fruit extract Protection method.
(25) A method for inhibiting vascular endothelial cells using a composition for suppressing a vascular injury marker comprising, as an active ingredient, at least one selected from the group consisting of Amla fruit, Amla fruit juice, Amla fruit extract and Amla fruit extract. Protection method.
(26) A vascular endothelial cell using a vascular injury marker-suppressing composition containing, as an active ingredient, at least one selected from the group consisting of Amla fruit, Amla fruit juice, Amla fruit extract and Amla fruit extract Protection method.
(27) The method for protecting vascular endothelial cells according to the above (25) or (26), wherein the organism is an organism excluding humans.
(28) Use of an extract obtained by extracting at least one selected from the group consisting of Amla fruit and Amla juice, which is a method for producing a vascular disorder marker-suppressing composition containing amla as an active ingredient A method for producing a composition for suppressing a vascular disorder marker, comprising:
(29) A method for producing a vascular disorder marker-suppressing composition containing amla as an active ingredient, wherein at least one raw material selected from the group consisting of amla fruit and amla fruit juice is water, base, acid and hydrophilicity A method for producing a vascular disorder marker inhibiting composition, characterized by using at least one selected from the group consisting of a solvent and using the extract obtained thereby.
(30) A method for producing a vascular disorder marker-suppressing composition containing amla as an active ingredient, wherein at least one raw material selected from the group consisting of amla fruit and amla juice is extracted with water. A method for producing a vascular dysfunction marker-suppressing composition, comprising using a product.

  The composition for suppressing a vascular disorder marker of the present invention has a high effect of protecting vascular endothelial cells, and therefore it is used for food and drink, etc. to suppress the formation of a thrombus, thereby causing stroke, cerebral hemorrhage, cerebral infarction, heart failure, myocardium Cardiovascular diseases such as infarction and heart failure can be prevented.

Claims (9)

  A composition that regulates a quantitative change of a marker protein for dysfunction of endothelial cells secreted into blood by vascular endothelial cell injury, comprising Amla fruit, Amla juice, Amla fruit extract, and Amla A vasopathic marker inhibitor composition comprising at least one selected from the group consisting of fruit juice extracts as an active ingredient, wherein the marker protein is von Willebrand factor or thrombomodulin.   The extract according to claim 1, wherein at least one selected from the group consisting of Amla fruit and Amla juice is extracted with a non-organic solvent. Inhibiting composition.   The composition for inhibiting a vascular injury marker according to claim 1 or 2, comprising a fraction of the extract according to claim 1 in an organic solvent as the active ingredient.   The fraction obtained by purifying the Amla fruit, Amla juice, or extract thereof according to claim 1 purified with an enzyme is contained as the active ingredient. The composition for suppressing a vascular injury marker according to claim 1.   The composition according to claim 4, wherein the enzyme according to claim 4 is a hydrolase.   A food or drink comprising the vascular disorder marker suppressing composition according to any one of claims 1 to 5.   A feed comprising the vascular disorder marker-suppressing composition according to any one of claims 1 to 5.   A quasi-drug containing the composition for suppressing a vascular disorder marker according to any one of claims 1 to 5.   A pharmaceutical comprising the vascular disorder marker suppressing composition according to any one of claims 1 to 5.

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