JP2006089383A - Thrombus preventing composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a thrombus preventing composition usable for a wide variety of foods and beverages, and a food and beverage, a quasi medicine and a medicine containing the same. <P>SOLUTION: This thrombus preventing composition comprises Hizikia fusiforme or its extract. The thrombus preventing composition comprises an extract of Hizikia fusiforme preferably extracted with at least one kind selected from the group consisting of water, a base, an acid, a hydrophilic solvent and acetone. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a thrombus-preventing composition containing hijiki or an extract thereof, and foods and drinks and pharmaceuticals containing the composition.

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 impeding blood circulation, so that the blood cannot normally supply nutrients and oxygen in cells and tissues, Problems such as the inability to discharge cell and tissue waste and accumulation of toxicity will occur.
In blood vessels, the symptoms caused by blood clots called blood clots are called thrombosis in a broad sense (hereinafter simply referred to as “thrombosis” in the broad sense) and are caused by blood clots. The pathological condition 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, aspirin that inhibits blood coagulation by inhibiting the adhesion of platelets to the blood vessel wall, heparin (Heparin), coumarin (Coumarin) that blocks the body's intrinsic blood coagulation pathway ) 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. Also, tissue-type plasminogen activator (tPA) is considered to be an ideal thrombolytic agent because of its high selectivity for thrombus, but there are some differences as a result of actual application to clinical treatment. However, there were side effects such as general 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 skin (for example, see Patent Document 1) are known, but there are problems with flavor and properties, and they are widely applied to foods. could not.
In addition, recently, a patent for a kiwifruit extract (for example, see Patent Document 2) has been published, but there is a drawback that the activity in the neutral range is weak.

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

  An object of the present invention is to provide a thrombus preventing composition that can be used for a wide variety of foods and drinks, and foods and drinks, quasi drugs, and pharmaceuticals containing the same.

  As a result of diversified studies for the purpose of searching for anticoagulant components using various natural plants, the present inventors have found that the enzyme-treated product of hijiki or its extract has an excellent anticoagulant effect, The present invention has been completed.

The thrombus prevention composition containing the hydrangea or an extract thereof obtained by the present invention inactivates a factor involved in the intrinsic pathway from the result of measuring the activated partial thromboplastin time (APTT). It was found that the effect of inhibiting fibrin formation and suppressing thrombus formation in blood vessels is high.
In particular, hijiki is derived from a natural plant that humans have been using for daily diets, and unlike conventional drugs, it is safe without side effects that cause bleeding in the body.
The present invention uses a thrombus or a thrombus-preventing composition containing an extract thereof for various foods and beverages, pharmaceuticals, etc., and suppresses the formation of thrombus, thereby preventing cerebral hemorrhage, cerebral infarction, myocardial infarction, arteriosclerosis and coronary artery disease. Such cardiovascular diseases can be prevented.

  The hijiki used in the present invention is a scientific name: Hijikia fusiforumis, and is a brown algae and a seaweed belonging to the genus Honda. It is a specialty of the sea near Japan, distributed along the Pacific coast in the south of Hidaka, Hokkaido, the Seto Inland Sea, the Sea of Japan side in the west of Hyogo Prefecture, and the coast of Kyushu. Dry matter is blackish brown, but it is yellowish brown when raw. Hijiki grows on the rocky open ocean reefs near the low tide. The body grows dark greenish brown, the roots are intertwined fibers, and grow on the rocks. The stem of the body is cartilaginous, cylindrical, 3-4 mm in thickness, 0.5-1 mm in length, flank elongated cylindrical leaves and twigs from the stem, and the leaves are succulent and flat in juveniles, in adults The leaves are linear and 3-10cm, many have sharp tips and firm inside, but often have a pin-like shape with bulging tips, or hollow and air bubbles, and thrive from spring to early summer. Dried hijiki is a lot of astringency that can't be eaten raw, but it can be removed by boiling in an iron kettle for several hours to remove the astringency and remove the pigment. Of the dried hijiki, a collection of only twigs is called “bud bud, rice hijiki or himehijiki”, and a long stem-like portion (main shaft portion) is called “long hijiki”. When the sprout is put back in the water, it will triple in bulk and about 6 times in weight. As another name, Hizuki is also called Nehi, Chosen Hijiki, Michihijiki, etc.

In the present invention, the portion of the elbow is not particularly limited, but a twig portion and a main shaft portion are used. The form is not particularly limited, and any of raw hijiki, dried hijiki, dried hijiki, hijiki powder and the like may be used.
In the case of hijiki powder, it can be used as it is, but since it contains a water-insoluble component, it is preferable that the water-insoluble component is removed by extraction.
In the case of using raw hijiki, dried hijiki, and dried hijiki during extraction, it is preferable to use one that has been crushed and homogenized by a mixer or the like in order to increase extraction efficiency.
When using dried hijiki or dried hijiki, it is preferably pulverized to a particle size of 40 mesh or less in order to increase extraction efficiency.

The extraction method is not particularly limited, such as extraction solvent and extraction temperature, and water, base, acid, hydrophilic solvent, and acetone can be used as the extraction solvent. The hydrophilic solvent is preferably one or more selected from the group of lower alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, and butyl alcohol from the viewpoint of operability and extraction efficiency. Particularly preferred is water, base, or acid.
When using an acid or a base 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. 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 more preferable to use water.
The acid used at this time is not particularly limited, and most of the acid can be used. However, it is preferable to use one kind or a combination of both selected from hydrochloric acid and sulfuric acid because of easy availability and operability. is there.
Further, the base is not particularly limited, and most of the bases can be used, but preferably one kind selected from sodium hydroxide and potassium hydroxide or a combination of both.
The concentration of the acid or base used for the extraction is not particularly limited and varies depending on the strength of the acid or base. However, from the viewpoint of operability and extraction efficiency, a concentration of 0.01 to 0.5 mol is used. It is preferable to use it.

The above extract can be used as it is, but it is preferable because removal of insoluble substances and solvent by filtration, centrifugation and fractionation increases the effect of preventing thrombus and widens the application range.
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 preventing thrombus is further enhanced. As an organic solvent, methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, lower alcohol such as butyl alcohol, ethyl acetate, butyl acetate, diethyl ether, methyl ether, methyl isobutyl ketone, hexane, acetone or chloroform can be used. In order to increase the purity of the soluble fraction, partitioning with other hydrophobic solvents can be combined. The concentration of these solvents is not particularly limited, but the final concentration is preferably 20 to 80% and more preferably 20 to 60% from the viewpoint of yield and effect.
In order to further increase the purity, it is also possible to use a hydrophobic resin based on phenol, styrene, acrylic acid, epoxyamine, pyridine, methacryl or the like. In that case, as an eluent after resin adsorption, lower alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, and 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, the effect of preventing thrombus can be confirmed, for example, by measuring activated partial thromboplastin time (APTT), which is a method of measuring anticoagulant activity against an endogenous blood coagulation system.

The thrombus preventing composition of the present invention can be applied to foods and drinks, pharmaceuticals, feeds, and the like, and preferably foods and drinks or pharmaceuticals that can be easily consumed by humans.
The food and drink in the present invention is not particularly limited as long as it is a form that can be taken orally, such as a solution, suspension, powder, or solid molded product. More specifically, 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 drinks, tea drinks Beverages such as powdered beverages, concentrated beverages, nutritional beverages, alcoholic beverages, bread, pasta, noodles, cake mixes, flour products such as fried flour, bread crumbs, rice cakes, caramel, chewing gum, chocolate, cookies, biscuits, cakes, Pastries such as pies, snacks, crackers, Japanese confectionery, dessert confectionery, sauces, processed tomato seasonings, flavor seasonings, cooking mixes, sauces, dressings, soups, curry and stew ingredients, processed oils and fats , Butter, margarine, mayonnaise, etc., milk drinks, yogurt, lactic acid bacteria drinks, ice creams, cream Dairy products such as dairy products, frozen foods, processed fish products such as fish meat ham and sausage, fish paste products, livestock processed products such as livestock ham and sausages, agricultural canned products, jams and marmalades, pickles, boiled beans, cereals, etc. Examples thereof include nutritional foods, tablets, capsules and the like.

  The intake of the thrombus prevention composition of the present invention as a food or drink should be adjusted according to the disease state of the present invention, the body weight, age, constitution, physical condition, etc. of the sick person. The product can be appropriately selected in the range of 0.05 g to 20 g, preferably 0.1 g to 5 g. This can be taken once or several times a day depending on the state of the disease or the form of food.

In the present invention, various nutritional components can be strengthened when processed into a thrombus preventing composition or a food or drink containing the same.
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, minerals such as calcium, magnesium, iron, zinc and 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 one or more useful substances approved as other foods and food additives Can be used.

The quasi drugs and pharmaceuticals in the present invention can be prepared as oral preparations or injections according to conventional methods using excipients and other additives suitable for oral or parenteral administration. Preferred is an oral preparation, and most preferred is an oral solid preparation that can be easily taken and is easy to store and carry.
As oral solid preparations, tablets, powders, fine granules, granules, capsules, pills, sustained-release preparations and the like are used. In such solid preparations, appropriate pharmacologically acceptable carriers, excipients (eg starch, lactose, sucrose, calcium carbonate, calcium phosphate etc.), binders (eg starch, gum arabic, carboxymethylcellulose, Hydroxypropylcellulose, crystalline cellulose, alginic acid, gelatin, polyvinylpyrrolidone, etc.), lubricant (eg, stearic acid, magnesium stearate, calcium stearate, etc.), disintegrant (eg, carboxymethylcellulose, talc, etc.), etc. Tablets, powders, fine granules, granules, capsules, pills, sustained release agents, etc. can be prepared by the method. Oral liquid preparations include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs, etc., and generally used inert diluents such as purified water and ethanol. . In addition to the inert diluent, the composition may contain adjuvants such as wetting agents and suspending agents, sweeteners, flavors, fragrances and preservatives.
Examples of injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. 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 ethanol, polysorbate 80, and the like. Such compositions may further contain adjuvants such as preservatives, wetting agents, emulsifiers, dispersants, stabilizers (eg lactose), solubilizers (eg glutamic acid, aspartic acid). These are sterilized by, for example, 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 thrombus-preventing composition of the present invention as a pharmaceutical agent is appropriately determined according to the individual case in consideration of the administration route, disease symptoms, age of the administration subject, sex, etc. It is 1 mg to 40 mg / day, preferably 2 mg to 10 mg / day per kg body weight.

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

Example 1 Preparation 1 of Thrombus Prevention Composition
The dried hijiki was pulverized to 40 mesh or less, 3 L of distilled water was added to 100 g of the powder, and the mixture was extracted at 100 ° C. for 3 hours. Then, it centrifuged (8500 rpm, 10 minutes), the supernatant was filtered, and the extract and the residue were isolate | separated. The filtrate was concentrated under reduced pressure and then freeze-dried to obtain 23.8 g of a thrombus preventing composition A of the present invention. The yield was 23.8%.

(Test Example 1) Confirmation of thrombus prevention effect The blood coagulation meter (Coagulometer) using platelet poor plasma (Platelet Poor Plasma, PPP) obtained by separating the thrombus prevention effect of the thrombus prevention composition A of the present invention from human blood. The APTT was measured and evaluated.
To the reaction cuvette, 10 μL of a sample adjusted to 0.075, 0.15, 0.3, 0.5 mg / mL and 40 μL of PPP were added at 37 ° C. with the concentration of the thrombus preventing composition A of the present invention as the solid content concentration. The reaction was allowed for 1 minute. Thereafter, 50 μL of APTT reagent was added, and the mixture was further reacted at 37 ° C. for 2 minutes. Then, 50 μL of 25 mM calcium chloride was added, and the time until plasma was coagulated was measured to obtain APTT.
The results are shown in Table 1 below.
At this time, APTT was measured by the same method using heparin adjusted to 0.05, 0.1, 0.2 and 0.3 U / mL as a sample as a control. The following formula for calculating the heparin-like activity value (U / mg) is obtained from the relationship between the concentration of heparin and the APTT of heparin, and the heparin-like activity value with respect to heparin (1 U / mL) at each sample concentration is applied to the formula. Asked.
The results are shown in Table 2 below.

Heparin-like activity value (U / mg) = (0.1648 × Log (APTT of sample)) / sample concentration (mg / mL)

  According to the results in Table 2, in the thrombus preventing composition A of the present invention, the APTT increases with the increase in the concentration of the thrombus preventing composition, and the heparin-like activity value converted to heparin used as an anticoagulant is 0 on average. It was confirmed that the anticoagulant effect was as high as .36 U / mg.

Example 2 Preparation 2 of Thrombus Prevention Composition
The dried hijiki was pulverized to 40 mesh or less, 6 L of distilled water was added to 200 g of the powder, and the mixture was extracted at 100 ° C. for 3 hours. Centrifugation (8500 rpm, 10 minutes), the supernatant was filtered, and the extract and the residue were separated. Thereafter, 6 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 400 mL. Ethanol was added to this concentrated solution to prepare 500 mL (final ethanol concentration 20%), and then allowed to stand at room temperature for 24 hours to precipitate insoluble components. The precipitate was separated by centrifugation (8500 rpm, 10 minutes), 1 L of distilled water was added to the precipitate and redissolved, and the precipitate was filtered to remove insoluble components. The filtrate was concentrated under reduced pressure and freeze-dried to obtain 16.4 g of a thrombus preventing composition B of the present invention. Further, ethanol was added to the concentrate obtained in the same manner to precipitate insoluble components when the final ethanol concentration was 60% and 80%, and the same operation was performed to perform 21.4 g of the thrombus preventing composition C of the present invention and D25.2g was obtained. Further, ethanol was added to the supernatant having a final ethanol concentration of 60% to precipitate the ethanol to a final concentration of 80%, and the same operation was performed to obtain 2.8 g of the thrombus preventing composition E of the present invention.
Example 3 Preparation 3 of Thrombus Prevention Composition
The dried hijiki was pulverized to 40 mesh or less, 3 L of 50% ethanol water was added to 100 g of the powder, and the mixture was allowed to stand at room temperature for 3 days for extraction. Then, it centrifuged (8500 rpm, 10 minutes), the supernatant was filtered, and the extract and the residue were isolate | separated. The filtrate was concentrated under reduced pressure, and then freeze-dried to obtain 21.1 g of a thrombus preventing composition F of the present invention. The yield was 21.1%.

(Test Example 2) Confirmation of Thrombus Prevention Effect Thrombus Prevention Composition A Obtained in Example 1, Thrombus Prevention Composition B, D, E Obtained in Example 2 and Thrombus Prevention Composition Obtained in Example 3 APTT was measured at a concentration of 0.2 mg / mL as a solid content concentration for the product F. And it applied to the calculation formula of the heparin-like activity value (U / mg) of the test example 1, and the heparin-like activity value of each thrombus prevention composition was calculated | required. In addition, the sample was similarly prepared for the supernatant fraction with 80% ethanol in Example 2, and the heparin-like activity value was determined. The results are shown in Table 3.

  From Table 2, it was confirmed that the ethanol precipitation component obtained in Example 2 showed a high heparin-like activity value, and it was found that the excellent anticoagulant effect was included in the ethanol-precipitated portion of the water extract.

(Example 4) Preparation of thrombus preventing composition-containing food (tablet confectionery) Thrombus preventing composition A 5 g, lactose 30 g obtained in Example 1, DHA-containing powdered oil (Suncoat DY-5; manufactured by Taiyo Chemical Co., Ltd.) 12 g, 4 g of sucrose fatty acid ester and 4 g of yoghurt flavor are mixed, and this mixture is pressure-molded using a rotary tableting machine, and one tablet is 300 mg containing the thrombus prevention composition-containing food or beverage of the present invention (tablet confectionery) Got.

(Example 5) Preparation of beverage containing thrombus prevention composition 5 g of thrombus prevention composition B obtained in Example 2, 2.1 g of 1/5 concentrated grapefruit transparent juice, 30 g of erythritol, 2.5 g of citric acid crystals, citric acid Trisodium 0.5g, L-ascorbic acid 0.5g, calcium lactate 1.93g, CCP 0.15g, grapefruit flavor 1.0 are mixed and dissolved in water to make a total volume of 1000mL, and it is filled into a 100mL bottle. After sealing with a cap, the mixture was sterilized by heating at 90 ° C. for 30 minutes to obtain a thrombus preventing composition-containing food or drink according to the present invention.

(Example 6) Preparation of thrombus preventing composition-containing beverage (vegetable juice mixed drink) Thrombus preventing composition A 0.2 g obtained in Example 2 and guar gum degradation product (Sunfiber R; manufactured by Taiyo Chemical Co., Ltd.) 3 g Was added to, mixed and dissolved in 100 mL of a commercially available vegetable juice mixed beverage to obtain a thrombus preventing composition-containing food or beverage (vegetable juice mixed beverage) of the present invention.

(Example 7) Preparation of thromboprophylaxis composition-containing cookie After putting 4 g of the thromboprophylaxis composition D obtained in Example 2 and 200 g of commercially available cake mix powder into a container, add 35 g of butter and mix with wooden coconut. It was. 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. A thrombus prevention composition-containing cookie was obtained.

(Example 8) Preparation of thrombus-preventing composition-containing yogurt Thrombus-preventing composition C 10 g obtained in Example 2, commercially available skim milk (manufactured by Meiji Dairies Co., Ltd., protein content 34%) 0.95 kg, and commercially available salt-free 0.35 kg of butter (manufactured by Snow Brand Milk Products Co., Ltd.) was dissolved in 8 L of warm water, homogenized, and the total amount was adjusted to 10 L. Next, it is sterilized by heating at 90 ° C. for 15 minutes, cooled, inoculated with 0.03 kg of commercially available lactic acid bacteria starter (manufactured by Hansen) (0.02 kg of Streptococcus thermophilus and 0.01 kg of Lactobacillus bulgaricus), and mixed uniformly. Into a 100 mL container, filled, sealed, fermented at 37 ° C. for 20 hours, and then cooled to obtain a thrombus-preventing composition-containing yogurt of the present invention.

(Example 9) Preparation of oral liquid food containing thrombus preventing composition 100 mg sodium caseinate (manufactured by DMV), 85 g egg white enzyme degradation product (manufactured by Taiyo Kagaku Co., Ltd.), 200 g dextrin (manufactured by Matsutani Chemical Co., Ltd.) An aqueous phase was prepared in the tank. Separately, 90 g of MCT (manufactured by Kao Corporation), 35 g of palm oil (manufactured by Fuji Oil Co., Ltd.), 35 g of safflower oil (manufactured by Taiyo Oil & Fats Co., Ltd.), 1.4 g of lecithin (manufactured by Taiyo Chemical Co., Ltd.), antifoaming agent ( 2 g of Taiyo Kagaku 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, concentrated and spray-dried to prepare about 510 g of an intermediate product powder. To 500 g of this intermediate product powder, 10 g of the thrombus prevention composition B obtained in Example 2, 390 g of dextrin (manufactured by Matsutani Chemical Co., Ltd.), 45 g of guar gum degradation product (Sunfiber R; manufactured by Taiyo Chemical Co., Ltd.), a small amount of vitamins and minerals and Powdered flavor was added and mixed uniformly to obtain about 950 g of an oral liquid food containing a thrombus preventing composition.

(Example 10) Preparation of tablet containing thrombus prevention composition Thrombus prevention composition F10g obtained in Example 3, 5 g of crystalline cellulose, 13.8 g of corn starch, 32.5 g of lactose, and 3.3 g of hydroxypropylcellulose were mixed. Granulated. To this granulated product, 1.0 g of magnesium stearate is added and mixed uniformly, and the mixture is pressure-molded using a rotary tableting machine to obtain a tablet containing the thrombus prevention composition of the present invention having 130 mg per tablet. It was.

The embodiment of the present invention and the target product are as follows.
(1) A thrombus preventing composition comprising hijiki or an extract thereof.
(2) The thrombus prevention composition according to (1) above, wherein the extract of hijiki is extracted from water of hijiki with water, a base, an acid, and a hydrophilic solvent.
(3) The thrombus prevention composition according to (1) or (2) above, wherein the hijiki extract is extracted from the hijiki with water.
(4) Said (1) or (2), wherein 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 Thrombus prevention composition.
(5) The thrombus prevention composition as described in any one of (1) to (4) above, wherein the composition is fractionated from one or two or more organic solvents from a hijiki extract.
(6) The organic solvent is at least selected from the group consisting of methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, butyl alcohol, ethyl acetate, butyl acetate, diethyl ether, methyl ether, methyl isobutyl ketone, hexane, or chloroform. The thrombus prevention composition according to (4), wherein the composition is one type.
(7) The thrombus prevention composition according to any one of (1) to (4), wherein the hijiki or an extract thereof is fractionated with ethanol.
(8) The thrombus prevention composition according to any one of (1) to (4) above, wherein hijiki or an extract thereof is fractionated as a precipitation component with ethanol.
(9) The thrombus prevention composition according to the above (8), wherein the hijiki or the extract thereof has a concentration of 20 to 80% when fractionated with ethanol and is a precipitated fraction.
(10) The thrombus prevention composition according to the above (8), wherein the hijiki or an extract thereof is an ethanol concentration of 20 to 60% when fractionated with ethanol, and is a precipitated fraction thereof.
(11) The thrombus prevention composition according to any one of (1) to (10) above, wherein the purity of hijiki or an extract thereof is increased by chromatography or a column using a hydrophobic resin.
(12) The thrombus prevention composition according to the above (13), wherein the hydrophobic resin is a matrix such as phenol, styrene, acrylic acid, epoxyamine, pyridine, or methacryl.
(13) A food or drink comprising the thrombus prevention composition according to any one of (1) to (12).
(14) A pharmaceutical comprising the thrombus preventing composition according to any one of (1) to (12).
(15) A pharmaceutical comprising the thrombus preventing composition according to any one of (1) to (12).
(16) A feed comprising the thrombus preventing composition according to any one of (1) to (12).

  The thrombus prevention composition containing the hijiki extract obtained in the present invention inhibits the formation of fibrin, which is a number of factors involved in the intrinsic pathway of the blood coagulation system or the final stage, and suppresses the formation of thrombus. It is highly effective in preventing blood clots, and it can be used in various foods and beverages and pharmaceuticals to prevent cardiovascular diseases such as cerebral hemorrhage, cerebral infarction, myocardial infarction, arteriosclerosis and coronary arteropathy by suppressing the formation of thrombus. it can.

Claims (6)

A thrombus preventing composition comprising hijiki or an extract thereof. 2. The thrombus prevention composition according to claim 1, wherein the extract of hijiki is extracted from at least one selected from the group consisting of water, base, acid, hydrophilic solvent, and acetone. The organic solvent is at least one selected from the group consisting of methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, butyl alcohol, ethyl acetate, butyl acetate, diethyl ether, methyl ether, methyl isobutyl ketone, hexane, or chloroform. The thrombus preventing composition according to claim 2, wherein A food or drink comprising the thrombus prevention composition according to any one of claims 1 to 3. A quasi-drug containing the thrombus prevention composition according to any one of claims 1 to 3. A pharmaceutical comprising the thrombus preventing composition according to any one of claims 1 to 3.