JP2006137697A - Platelet aggregation prevention composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a platelet aggregation prevention composition usable for wide foods and drinks and to obtain foods, drinks, quasi medicines and medicines containing the same. <P>SOLUTION: This platelet aggregation prevention composition contains fruits, fruit juice or leaves of Hibiscus or their extracts. Preferably, the extracts of fruits, fruit juice or leaves of Hibiscus are extracted from fruits, fruit juice or leaves of Hibiscus 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

  TECHNICAL FIELD The present invention relates to a platelet aggregation preventing composition containing hibiscus fruit, fruit juice, leaf or an extract thereof, and a food and drink, a quasi-drug and a pharmaceutical containing the same.

The thrombus progresses to platelet thrombus due to adhesion and aggregation of platelets activated by various causes such as plaque rupture to the intima, and then to fibrin thrombus involving various coagulation factors such as fibrinogen. 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.

Serious thrombi that cause these heart diseases, cerebrovascular diseases, etc. differ from the fibrin thrombus formed under the blood flow band in terms of mechanism, and are formed in the presence of abundant blood flow such as arteries. It is thought that. In the bloodstream, even if the coagulation factor is activated, it is diluted by the bloodstream and thus does not lead to thrombus formation. However, platelets, a component that adheres to the damaged vessel wall and aggregates to increase local concentration, play an important role in the formation of thrombus.
When vascular endothelial cells are damaged and detached, collagen in vascular endothelial subcellular tissue is exposed, and von Willebrand factor (vWF: Factor VII) synthesized in vascular endothelial cells causes collagen and vWF receptor (GpIb) to be separated. Crosslinks are formed (adhered) on Furthermore, platelets are activated by agonists such as thrombin, and are bound to other platelets via fibrinogen by fibrinogen receptor (GpIIb-IIIa), causing platelet aggregation and forming platelet thrombus. Therefore, whether fibrinogen and other serum proteins can inhibit the binding of GpIIb-IIIa is one important requirement for preventing thrombus formation.
Agonosine released from vascular platelets and damaged blood cells, endothelium or tissues by various substances such as collagen and thrombin as agonists that promote binding with other platelets via fibrinogen by this GpIIb-IIIa There is diphosphate (ADENOSINE 5 'DIPHOSPHAPE SODIUM: ADP).

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 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, but 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 an antiplatelet therapeutic agent for preventing diseases such as myocardial infarction, but aspirin has no effect on platelet aggregation induced by ADP, and thus has an effect on platelet aggregation. However, there are side effects such as gastrointestinal disorders. Therefore, in the field of foods and pharmaceuticals, there is a demand for antiplatelet therapy drugs that are highly safe, inexpensive and highly practical.
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 platelet aggregation 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 research for the purpose of searching for anticoagulant components using various natural plants, the present inventors have found that hibiscus fruits, fruit juices, leaves or extracts thereof have excellent antiplatelet aggregation activity. The present invention was completed.

The composition for preventing platelet aggregation containing the hibiscus fruit, fruit juice, leaf or extract thereof obtained by the present invention is an agonist that induces platelet aggregation by causing a binding stage with other platelets via fibrinogen by GpIIb-IIIa From the results measured by the so-called ADP-induced platelet aggregation test when the ADP was added, the platelet aggregation preventing composition showed that GpIIb-IIIa suppresses the binding stage with other platelets via fibrinogen. It was found that the effect of suppressing the formation of aggregated thrombus is high.
The present invention uses a composition for preventing platelet aggregation containing hibiscus or an extract thereof in various foods and beverages, pharmaceuticals, and the like, and suppresses thrombus formation due to platelet aggregation, thereby causing stroke, cerebral hemorrhage, cerebral infarction, heart failure, myocardium Cardiovascular diseases such as infarction and heart failure can be prevented.

  The hibiscus used in the present invention is called the scientific name: Hibiscus, and the Japanese name is called Bussouge (French Mulberry). Hibiscus is an evergreen shrub belonging to the genus Fuyo, and its origin is derived from the ancient Egyptian beauty goddess Hibisu. The place of origin is southern China southern China, eastern India, the South Pacific Islands, and tropical Africa. Hibiscus has a refreshing acidity, and recently it has been used as a source for French and Italian cuisine. The edible hibiscus used as herbs is the scientific name Hibiscus Sabdarifa / (UK) Roselle, (USA) Florida Cranberry It has been cultivated in countries such as Jamaica, Sudan, Egypt, Thailand, China, Suriname, and Malaysia.

In the present invention, fruits, fruit juices, leaves or extracts thereof are used as the hibiscus site, and preferably the fruit petals or leaf portions derived from strawberries and flowers are used. The form is not particularly limited, and any of fresh fruits, dried fruits, fruit powders, fresh leaves, dried leaves, dried leaf powders and the like may be used.
In the case of fruit juice or fruit juice powder, it can be used as it is, but since it contains water-insoluble components such as fresh fruits, dried fruits, fresh leaves or dried leaves, it is preferable that the water-insoluble components are removed by extraction.
In the case of using fresh fruits, dried fruits, fresh leaves, or dried leaves during extraction, it is preferable to use those that have been crushed and homogenized by a mixer or the like in order to increase the extraction efficiency.
In the case of using dried fruits or dried leaves, 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 acids can be used, but one or both of hydrochloric acid and sulfuric acid selected from the viewpoint of availability and operability are used. Use in combination is preferred.
The base is not particularly limited, and most of the bases can be used, but one kind selected from sodium hydroxide and potassium hydroxide or a combination of both is preferable.
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, and varies depending on the strength of the acid or base. From the viewpoint of efficiency, it is preferable to use a concentration of 0.01 to 0.5 mol.

In the above extraction, enzymes such as pectinase, protease, tannase, or cellulase can be used alone or in combination of two or more.
Further, in the above extraction, it is preferable to repeat the extraction step once or more for the extraction residue, because the extraction efficiency is improved and the yield is improved. The solvent used for extraction in this case may be the same, or another solvent may be used.

The above extract can be used as it is, but it is preferable because the antiplatelet aggregation effect is enhanced and the application range is widened by removing insoluble substances and solvent by filtration, centrifugation and fractional distillation.
After removing the insoluble substances and the solvent, the fruit juice or the extract is directly or after concentration, and then distributed using an organic solvent to obtain each solvent-soluble fraction. These solvent-soluble fractions are preferred because the antiplatelet aggregation effect 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, distribution with other hydrophobic solvents can be combined, but ethyl alcohol is preferred. 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 and 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, antiplatelet aggregation means suppression of platelet aggregation, and is also simply called antiplatelet (Antiplatelet). The anti-platelet aggregation activity is an agonist that causes platelet aggregation by causing a binding stage with other platelets via fibrinogen by GpIIb-IIIa in the collected blood using, for example, a whole blood platelet aggregation measuring device (Agregometer). This can be confirmed by a method of measuring the platelet aggregation rate when a certain ADP is added.

The platelet aggregation 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 or drink in the present invention is not particularly limited as long as it is in a form that can be taken orally, such as a solution, suspension, powder, 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 amount of the composition for preventing platelet aggregation of the present invention as a food or drink should be adjusted according to the disease state of the present invention, the weight, age, constitution, physical condition, etc. of the sick person. The preventive composition 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 one to several times a day depending on the state of the disease and the form of food.

In this invention, when processing into a platelet aggregation prevention composition or food-drinks containing it, various nutrient components can be strengthened.
Nutritional ingredients that can be strengthened include vitamins such as vitamin A, vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, vitamin D, vitamin E, niacin (nicotinic acid), pantothenic acid, folic acid, Essential amino acids such as lysine, threonine and tryptophan, 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 ethyl alcohol. Including. 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 ethyl alcohol, 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 platelet aggregation preventing composition of the present invention as a pharmaceutical is appropriately determined according to individual cases in consideration of the administration route, disease symptoms, age of the administration subject, sex, etc. The active ingredient per person is about 40 mg to 3 g / day, preferably 100 to 500 mg / day.

  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 a platelet aggregation preventing composition
Hibiscus dried buds and petals were crushed to 40 mesh or less, 3 L of distilled water was added to 150 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 29.8 g (yield 19.9%) of the platelet aggregation preventing composition A of the present invention.

(Example 2) Preparation 2 of a platelet aggregation preventing composition
The dried leaves of hibiscus were pulverized to 20 mesh or less, 2 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 13.4 g (yield 13.4%) of the platelet aggregation preventing composition B of the present invention.

(Test Example 1) Confirmation of antiplatelet aggregation activity 1
The anti-platelet aggregation activity of the anti-platelet aggregation composition of the present invention was measured after adding 5 μL of sample to 200 μL of healthy human blood using a whole blood platelet aggregation capacity measuring device (WBA-Neo: manufactured by AISK). Then, 22 μL of ADP (manufactured by Sigma: 100 mg / vial) adjusted to a final concentration of 10 μM was added as a substance causing aggregation, and the platelet aggregation rate after 5 minutes was measured.
Separately, water (sample concentration 0 mg / mL) was added as a control, and the platelet aggregation rate was measured by the same method. From the measured platelet aggregation rate, antiplatelet aggregation activity (%) relative to the control was calculated according to the following formula.
Antiplatelet aggregation activity (%) = (control platelet aggregation rate−platelet aggregation rate at the time of sample addition) / control platelet aggregation rate × 100
Table 1 shows the results of measurement using samples prepared by diluting the platelet aggregation preventing composition with distilled water to 1.25, 2.5, and 5.0 mg / mL.

  The results of Table 1 above suggest that the anti-platelet aggregation composition of the present invention has an anti-platelet aggregation effect by inhibiting the binding stage with other platelets via fibrinogen by GpIIb-IIIa related to ADP in platelet aggregation. It was. It was also confirmed that the antiplatelet aggregation activity was proportionally increased by increasing the concentration of the antiplatelet aggregation composition.

(Example 3) Preparation 3 of a platelet aggregation preventing composition
Hibiscus dried buds and petals were crushed to 40 mesh or less, 3 L of distilled water was added to 150 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 to 400 mL. Ethyl alcohol was added to this concentrated solution to prepare 500 mL (final ethyl alcohol 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), the supernatant was concentrated under reduced pressure, and 1 L of distilled water was added to redissolve. Then, the insoluble component was removed by filtration, and the filtrate was concentrated under reduced pressure and lyophilized to obtain 12.4 g (yield 8.3%) of the platelet aggregation preventing composition C of the present invention. In addition, ethyl alcohol is added to the concentrated solution obtained in the same manner to precipitate insoluble components when the final ethyl alcohol concentration is 60% and 80%, and the same operation is performed to each of the platelet aggregation preventing compositions of the present invention. D9.8g (yield 6.5%) and E6.7g (yield 4.5%) were obtained.

(Test Example 3) Confirmation 2 of antiplatelet aggregation activity
With regard to the platelet aggregation preventing compositions C, D and E obtained in Example 3, the platelet aggregation rate was measured at the concentration of 5.0 mg / mL by the same method as in Test Example 1, and the antiplatelet aggregation activity was calculated. As a result, it was confirmed that antiplatelet aggregation activity (%) showed higher antiplatelet aggregation effect by fractionating 79.2, 81.4 and 83.6 with ethyl alcohol, respectively.
In Example 3, the platelet aggregation rate was measured in the same manner for the precipitated component at a final ethyl alcohol concentration of 20% and the antiplatelet aggregation activity was calculated. As a result, the antiplatelet aggregation activity (%) was 11.9. It was found that antiplatelet aggregation was contained in the ethyl alcohol soluble fraction.

(Example 4) Preparation of platelet aggregation preventing composition-containing food (tablet confectionery) Platelet aggregation preventing composition A5g, lactose 30g, DHA-containing powdered oil obtained in Example 1 (Suncoat DY-5; Taiyo Kagaku Co., Ltd.) 12 g, 4 g of sucrose fatty acid ester, and 4 g of yoghurt flavor, and the mixture is pressure-molded using a rotary tableting machine, and 1 tablet is 300 mg of the present invention containing the platelet aggregation preventing composition of the present invention ( Tablet confectionery) was obtained.

(Example 5) Preparation of beverage containing platelet aggregation preventing composition B5g platelet aggregation preventing composition B obtained in Example 2, 2.1 g of 1/5 concentrated grapefruit transparent fruit juice, 30 g of erythritol, 2.5 g of citric acid crystals, Trisodium citrate 0.5g, L-ascorbic acid 0.5g, calcium lactate 1.93g, CCP 0.15g, grapefruit fragrance 1.0 are mixed and dissolved in water to make a total volume of 1000mL, and it is put into a 100mL bottle. After filling and sealing with a cap, it was sterilized by heating at 90 ° C. for 30 minutes to obtain a food and drink containing the platelet aggregation preventing composition of the present invention.

Example 6 Preparation of Platelet Aggregation Prevention Composition-Containing Beverage (Vegetable Fruit Juice Mixed Beverage) Platelet aggregation prevention 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 food and drink (vegetable juice mixed beverage) containing the platelet aggregation preventing composition of the present invention.

Example 7 Preparation of Cookies Containing Platelet Aggregation Prevention Composition Cookies After 4 g of platelet aggregation prevention composition B obtained in Example 2 and 200 g of commercially available cake mix powder were placed in a container, 35 g of butter was added and Mixed. 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. The platelet aggregation preventing composition-containing cookie was obtained.

Example 8 Preparation of Yogurt Containing Platelet Aggregation Prevention Composition 1 g of Platelet Aggregation Prevention Composition A obtained in Example 1, 95 g of commercially available skim milk (manufactured by Meiji Dairies Co., Ltd., protein content 34%), and commercially available unsalted salt 35 g of 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, the mixture is sterilized by heating at 90 ° C. for 15 minutes, cooled, 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), mixed uniformly, and divided into a 100 mL container. Note, filled, sealed, fermented at 37 ° C. for 20 hours and then cooled to obtain the platelet aggregation preventing composition-containing yogurt of the present invention.

(Example 9) Preparation of an oral liquid food containing a platelet aggregation preventing composition 50 mg sodium caseinate (DMV), 42.5 g egg white enzyme degradation product (Taiyo Kagaku), 100 g dextrin (Matsuya Chemical) in 1 liter of water Dissolved and 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, 4 g of the platelet aggregation preventing composition A obtained in Example 1, 156 g of dextrin (manufactured by Matsutani Chemical Co., Ltd.), 18 g of guar gum degradation product (Sunfiber R; manufactured by Taiyo Chemical Co., Ltd.), a small amount of vitamins and minerals And powdered fragrance were added and mixed uniformly to obtain about 380 g of an oral liquid food containing a platelet aggregation preventing composition.

Example 10 Preparation of Tablet Containing Platelet Aggregation Prevention Composition-Containing Tablet 10 mg of platelet aggregation prevention composition A obtained in Example 1, 5 g of crystalline cellulose, 13.8 g of corn starch, 32.5 g of lactose, and 3.3 g of hydroxypropylcellulose Mixed and granulated. To this granulated product, 1.0 g of magnesium stearate is added, mixed uniformly, and the mixture is pressure-molded using a rotary tableting machine to obtain a tablet containing the platelet aggregation preventing composition-containing tablet of the present invention having 130 mg each. Obtained.

The embodiment of the present invention and the target product are as follows.
(1) A platelet aggregation-preventing composition comprising hibiscus fruit, fruit juice, leaf or an extract thereof.
(2) The hibiscus fruit, fruit juice or leaf extract is extracted from water, base, acid or hydrophilic solvent from the hibiscus fruit, fruit juice or leaf. (1) The composition for preventing platelet aggregation according to (1).
(3) The platelet aggregation preventing composition according to (1) or (2) above, wherein the extract of hibiscus fruit, fruit juice, or leaf is extracted from the fruit, fruit juice, or leaf of hibiscus 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 A platelet aggregation preventing composition.
(5) The platelet aggregation according to any one of (1) to (4) above, wherein the platelet aggregation is fractionated from an extract of a hibiscus fruit, fruit juice or leaf by any one or more organic solvents. Prophylactic composition.
(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 composition for preventing platelet aggregation according to (5) above, wherein the composition is one type.
(7) The platelet aggregation preventing composition according to any one of (1) to (4) above, wherein the hibiscus fruit, fruit juice, leaf or extract thereof is fractionated with ethyl alcohol.
(8) The platelet aggregation preventing composition according to any one of (1) to (4) above, wherein the hibiscus fruit, fruit juice, leaf or extract thereof is fractionated as a precipitation component with ethyl alcohol.
(9) The hibiscus fruit, fruit juice, leaf or extract thereof has an ethyl alcohol concentration of 20 to 80% when fractionated with ethyl alcohol, and is an ethyl alcohol-soluble fraction. The composition for preventing platelet aggregation according to (8) above.
(10) The hibiscus fruit, fruit juice, leaf or extract thereof has an ethyl alcohol concentration of 20 to 60% when fractionated with ethyl alcohol, and is an ethyl alcohol-soluble fraction. The composition for preventing platelet aggregation according to (8) above.
(11) Prevention of platelet aggregation according to any one of (1) to (10) above, wherein the purity of the hibiscus fruit, fruit juice, leaf or extract thereof is enhanced by chromatography or a column using a hydrophobic resin. Composition.
(12) The platelet aggregation preventing composition according to (11) above, wherein the hydrophobic resin is based on phenol, styrene, acrylic acid, epoxyamine, pyridine, methacryl and the like.
(13) A food or drink comprising the platelet aggregation preventing composition according to any one of (1) to (12).
(14) A pharmaceutical comprising the platelet aggregation preventing composition according to any one of (1) to (12).
(15) A pharmaceutical product comprising the platelet aggregation preventing composition according to any one of (1) to (12).
(16) A feed comprising the platelet aggregation preventing composition according to any one of (1) to (12).

  The composition for preventing platelet aggregation comprising a hibiscus fruit, fruit juice, leaf or extract thereof obtained by the present invention is capable of binding to other platelets via fibrinogen by GpIIb-IIIa related to ADP in platelet aggregation. Anti-platelet aggregation effect by suppressing the stage is high, and it is used for various foods and beverages and pharmaceuticals, etc. By suppressing the formation of thrombus by the platelet aggregation preventing composition, stroke, cerebral hemorrhage, cerebral infarction, heart failure, myocardial infarction, heart Cardiovascular diseases such as paralysis can be prevented.

Claims (7)

A platelet aggregation-preventing composition comprising a hibiscus fruit, fruit juice, leaf, or an extract thereof. The hibiscus fruit, fruit juice or leaf extract is extracted from the hibiscus fruit, fruit juice or leaf with at least one selected from the group consisting of water, base, acid, hydrophilic solvent and acetone. The composition for preventing platelet aggregation according to claim 1. The composition for preventing platelet aggregation according to claim 1 or 2, comprising a fraction of an extract of hibiscus fruit, fruit juice or leaf with an organic solvent. 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 composition for preventing platelet aggregation according to claim 3, wherein A food or drink comprising the platelet aggregation preventing composition according to any one of claims 1 to 4. A quasi-drug comprising the platelet aggregation preventing composition according to any one of claims 1 to 4. A pharmaceutical comprising the platelet aggregation preventing composition according to any one of claims 1 to 4.