JP2005162684A - Antithrombotic composition - Google Patents
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本発明は、抗血栓組成物及びそれを含有する飲食品に関する。 The present invention relates to an antithrombotic composition and a food or drink containing the same.
血栓は、フィブリノーゲンというタンパク質が活性化され、フィブリンに転換されながら、血小板、白血球等と共に、不溶性の重合体となって血管の内壁に固まってできる。身体が正常なときには、この血栓のもととなるフィブリンを溶かす働きをする線溶酵素が血栓予防をして、線溶酵素が不足するとフィブリンを溶解できなくなり、血栓ができるようになる。
形成された血栓は血管に沈着し、血管の断面積を減少させ、血液の循環を阻害し、その結果、血液が細胞及び組職で栄養分と酸素を正常に供給することができず、また、細胞及び組織の老廃物を排出できなくなり、毒性が蓄積される等の問題点が発生するようになる。
血管の中で、血栓といわれる血液の固まりが引き起こす症状を広義の血栓症（以下、単に「血栓症」と記載した場合は、広義の血栓症をいう）と呼び、血栓が原因になって起こる病態は狭義の血栓症と塞栓症に分けられる。狭義の血栓症は血栓が形成個所で血流を部分的にあるいは完全に閉塞することによる症状で、塞栓症は血栓が形成個所から剥がれて血流によって移動し、他の個所で血流を部分的にあるいは完全に閉塞することによって起こる病態のことを指す。
このような血栓症は血栓が生じた血管の部位によって多様な疾病を誘発するようになる。その中でも特に脳血管や心臓血管に生じた場合には脳卒中、脳出血、脳梗塞、心不全症、心筋梗塞、心臓麻痺等深刻な症状が発生し、半身不随を引き起こし、ひどい場合には死亡することもある。
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.
現在、血栓症を解決するために、血栓の生成を抑制する抗血栓剤及び血栓形成予防剤と、生成された血栓を溶解させる血栓溶解剤の研究開発が主に行われている。
抗血栓剤又は血栓形成予防剤としては、血管壁への血小板の付着を阻害することで血液の凝固を阻害するアスピリンと、体内の内因性血液凝固経路を遮断するヘパリン（Ｈｅｐａｒｉｎ）、クマリン（Ｃｏｕｍａｒｉｎ）等が現在臨床で使われている。また最近はエイコサペンタエン酸（ＥＰＡ）、プロスタサイクリン（Ｐｒｏｓｔａｃｙｃｌｉｎｅ；ＰＧ１２）誘導体等が商品化されている。しかし、これら薬剤は特異性がないため、生体内においては血栓以外の部分にも影響を及ぼし、生体内に残存した場合、出血等を引き起こす可能性がある。その他に、ヒルジン（ｈｉｒｕｄｉｎ）、合成抗トロンビン（ｓｙｎｔｈｅｔｉｃ ａｎｔｉｔｈｒｏｍｂｉｎ）、チクロピジン（Ｔｉｃｌｏｐｉｄｉｎ）等の抗血栓活性についても報告されているが、まだ実用化には至っていない。
血栓溶解剤としては、ストレプトキナーゼ（ｓｔｒｅｐｔｏｋｉｎａｓｅ）、ウロキナーゼ（ｕｒｏｋｉｎａｓｅ）のようなプラスミノゲンアクチベーター（ｐｌａｓｍｉｎｏｇｅｎ ａｃｔｉｖａｔｏｒ）を血栓が生成された患者に静脈注射して、体内の血栓溶解系を活性化する治療法が一般的に使われている。これらが血栓を溶解させる効果は、幾多の臨床実験で立証されたが、抗血栓剤又は血栓形成予防剤と同様、血栓に対する特異性が無く、血栓を治療する間に全身出血する等の副作用がある。また組職型プラスミノゲンアクチベーター（ｔｉｓｓｕｅ−ｔｙｐｅ ｐｌａｓｍｉｎｏｇｅｎ ａｃｔｉｖａｔｏｒ，ｔＰＡ）は血栓に対する選択性が高く、理想的な血栓溶解剤と考えられたが、実際に臨床治療に適用した結果、程度の差はあるが相変らず全身出血等の副作用があった。また血液内での半減期が非常に短く、薬効の持続時間が短いため、体内で薬効を維持するためには投与量が多くなければならず、そのため治療費用が従来の血栓溶解剤に比べ非常に高いという問題点がある。
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.
このような医薬品が血栓の生成予防に使用されてはいるものの、血栓除去にあまり著しい効果を現わすことが無く、深刻な副作用を誘発するため、最近では、医薬品による治療よりは食生活を通じて病気を予防し、体質を調節又は活性化させる機能を持った成分又は食品成分に対する研究も注目されるようになってきている。
食品成分としては、ナットウキナーゼや多価不飽和脂肪酸、グルコサミン、タマネギの薄皮（例えば、特許文献１参照。）等の素材が知られているが、風味や性状等に問題があり、幅広く食品に応用できなかった。
また、最近では、キウイフルーツ抽出物（例えば、特許文献２参照。）についての特許が公開されたが、中性域での活性が弱いという欠点がある。
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.
本発明の課題は、幅広い飲食品に使用可能な抗血栓組成物及びそれを含有する飲食品を提供することにある。 An object of the present invention is to provide an antithrombotic composition that can be used for a wide variety of foods and drinks and foods and drinks containing the same.
本発明者らは様々な天然植物を利用して抗血栓成分を捜す目的で、多角的に研究検討した結果アムラーの果実、果汁及びそれらの抽出物に優れた抗血栓効果があることを見出し、本発明を完成させた。 The present inventors have found that there is an excellent antithrombotic effect in Amler's fruits, fruit juices and their extracts as a result of diversified research studies for the purpose of searching for antithrombogenic components using various natural plants, The present invention has been completed.
本発明で得られたアムラーの果実、果汁又はそれらの抽出物を含有する抗血栓組成物は、活性化部分トロンボプラスチン時間（Ａｃｔｉｖａｔｅｄ Ｐａｒｔｉａｌ Ｔｈｒｏｍｂｏｐｌａｓｔｉｎ Ｔｉｍｅ；ＡＰＴＴ）を測定した結果から、内因性経路に関与する因子を不活性化して、フィブリン形成を阻害し、血管内の血栓生成を抑制する効果が高いことがわかった。
特にアムラーは、昔から人間が日常食生活に使用してきた天然植物由来なので、従来使用していた薬剤とは違い、体内で出血を起こす副作用が無く安全である。
本発明はアムラーの果実、果汁又はそれらの抽出物を含有する抗血栓組成物を各種飲食品及び医薬品等に利用して、血栓の生成を抑制することで脳出血、脳梗塞、心筋梗塞、動脈硬化及び冠状動脈症のような心血関係疾患を予防することができる。
The antithrombotic composition containing Amler fruits, fruit juices or extracts thereof obtained in the present invention is involved in the intrinsic pathway from the result of measuring the activated partial thromboplastin time (APTT). It was found that the effect of inhibiting the formation of the factor, inhibiting fibrin formation, and suppressing thrombus formation in the blood vessel is high.
In particular, Amler is safe because it is derived from natural plants that humans have been using for a long time, because it has no side effects that cause bleeding in the body, unlike conventional drugs.
The present invention uses an antithrombotic composition containing Amler fruit, fruit juice or an extract thereof for various foods and beverages, pharmaceuticals, and the like, and suppresses thrombus formation, thereby causing cerebral hemorrhage, cerebral infarction, myocardial infarction, arteriosclerosis And cardiovascular diseases such as coronary artery disease can be prevented.
本願発明に用いるアムラーとは、学名：エンビリカ・オフィシナル（Ｅｍｂｌｉｃａ ｏｆｆｉｃｉｎａｌｅ）又は、フィランサス・エンブリカ（Ｐｈｙｌｌａｎｔｈｕｓ ｅｍｂｉｌｉｃａ）といい、トウダイグサ科コミカンソウ属に属する落葉の亜高木であり、インドからマレーシア地域及び中国南部にかけて分布しており、インドが原産地と考えられている。また、各地方又は言語により、各々固有の名称があり、余柑子、油甘、奄摩勒、エンブリック・ミロバラン、アーマラキー、マラッカノキ、マラッカツリー、インディアングーズベリー、アロンラ、アミラ、アミラキ、アミラキャトラ、ネリカイ、ネルリ、タシャ、カユラカ、ケムラカ、ナックホンポン等とも称されている。 Amler used in the present invention is a scientific name: Emblica officinale or Philanthus embrica, which is a sub-tree of deciduous leaves belonging to the genus Euphorbiaceae, from the Indian region to southern Malaysia and China. It is distributed over the country, and India is considered the origin. In addition, each region or language has its own unique name, such as citrus, oil sweets, Satsuma mushrooms, Emblic Mirobaran, Armala Key, Melaka tree, Malacca tree, Indian Gooseberry, Aronra, Amira, Amiraki, Amira Cattra, Nerikai, It is also called Neruri, Tasha, Kayuraka, Kemuraka, Nakhon Pong and others.
本発明において、アムラーの部位としては、果実を用いることができる。その形態は、特に限定するものではなく、未熟果実、完熟果実、乾燥果実、果汁、果汁粉末等のいずれでも良い。
果汁又は果汁粉末を用いる場合は、そのままでも使用できるが、生果実又は乾燥果実等、水不溶性成分を含む物を使用する場合は、抽出により、水不溶性成分が除去されていることが好ましい。
抽出の際、生果実を使用する場合は、種子を除去した後、水を添加又は無添加で、抽出効率を高めるためにミキサー等により破砕、均質化したものを用いることが好ましい。
乾燥果実を使用する場合は、抽出効率を高めるために４０メッシュ以下の粒度になるように粉砕されていることが好ましい。
In the present invention, fruit can be used as the Amler site. The form is not particularly limited, and any of immature fruit, ripe fruit, dried fruit, fruit juice, fruit juice powder, and the like may be used.
When using fruit juice or fruit juice powder, it can be used as it is, but when using a product containing a water-insoluble component such as fresh fruit or dried fruit, the water-insoluble component is preferably removed by extraction.
At the time of extraction, when using fresh fruits, it is preferable to use seeds that have been crushed and homogenized with a mixer or the like in order to increase extraction efficiency, with or without the addition of water.
When using a dried fruit, it is preferable to grind | pulverize so that it may become a particle size of 40 mesh or less, in order to improve extraction efficiency.
抽出方法は、抽出溶媒、抽出温度等、特に限定されるものではなく、抽出溶媒としては、水、塩基、酸、その他食塩水等の非有機溶媒を使うことができ、好ましくは、水、塩基、酸のいずれかである。
酸又は塩基を抽出溶媒で使う場合、抽出物を中和させることが好ましい。中和反応によって生成された塩は、透析法やゲル濾過等、公知の方法により、取り除くことができる。水を抽出溶媒として用いた場合には、上記のような中和反応は必要なく、生成された塩を取り除く必要もないため、水を用いることが更に好ましい。
この時使用する酸としては、特に限定するものではなく、大部分の酸を使うことができるが、好ましくは、塩酸、硫酸より選ばれる１種又は両者の併用である。
また、塩基としては、特に限定するものではなく、大部分の塩基を使うことができるが、好ましくは、水酸化ナトリウム、水酸化カリウムより選ばれる１種又は両者の併用である。
抽出に使用される酸又は塩基の濃度は、特に限定するものではなく、酸又は塩基の強さによって変化するが、０．０１〜０．５モルの濃度を使用することが好ましい。
The extraction method is not particularly limited, such as extraction solvent and extraction temperature. As the extraction solvent, water, base, acid, and other non-organic solvents such as saline can be used, preferably water, base , One of the acids.
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. 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 acids can be used, but one kind selected from hydrochloric acid and sulfuric acid or a combination of both is preferred.
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 extraction is not particularly limited, and varies depending on the strength of the acid or base, but it is preferable to use a concentration of 0.01 to 0.5 mol.
上記の抽出において、本願出願人が先に出願した特願２００３−２０９５４２で示したペクチナーゼの他、セルラーゼ等の酵素を併用することも可能である。
更に、上記の抽出において、抽出残渣に対して再度抽出工程を１回又はそれ以上繰り返すことで、抽出率が向上し、収率が向上するので、好ましい。この場合の抽出に用いる溶媒は、同じでも良いし、別の溶媒を用いても良い。
In the above extraction, an enzyme such as cellulase can be used in combination with the pectinase shown in Japanese Patent Application No. 2003-209542 previously filed by the applicant of the present application.
Further, in the above extraction, it is preferable to repeat the extraction step once or more for the extraction residue, since the extraction rate 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.
上記の果汁又は抽出物は、そのままでも使用できるが、濾過や遠心分離により、不溶性物質を取り除くことにより、抗血栓効果が高くなり、応用範囲も広がるので好ましい。
不溶性物質を取り除いた後、果汁又は抽出液をそのまま又は濃縮した後にエタノールを加えて得られる沈殿物を回収したものは、更に抗血栓効果が高くなるので好ましい。エタノールの濃度としては、特に限定するものではないが、収率及び効果の点より、エタノール濃度として６０〜９５％が好ましく、７０〜９０％が更に好ましい。
抽出物はそのままでの使用も可能だが、必要であれば噴霧乾燥や凍結乾燥等の手段により乾燥粉末化させて使用することも可能である。
The above-mentioned fruit juice or extract can be used as it is, but it is preferable because the antithrombotic effect is enhanced and the application range is widened by removing insoluble substances by filtration or centrifugation.
It is preferable to recover the precipitate obtained by adding ethanol after removing the insoluble substance as it is or after concentrating the fruit juice or extract, since the antithrombotic effect is further enhanced. Although it does not specifically limit as a density | concentration of ethanol, From the point of a yield and an effect, 60 to 95% is preferable as a ethanol concentration, and 70 to 90% is still more preferable.
The extract can be used as it is, but if necessary, it can also be used as a dry powder by means such as spray drying or freeze drying.
本願発明における抗血栓とは、特に限定されるものではないが、好ましくは、血栓の生成を抑制する作用（抗凝固作用）のことである。
本願発明において抗血栓効果は、例えば、内因性血液凝固システムに対する、抗凝固活性を測定する方法である、活性化部分トロンボプラスチン時間（ＡＰＴＴ）を測定することにより確認することができる。
The antithrombosis in the present invention is not particularly limited, but is preferably an action (anticoagulation action) that suppresses the formation of a thrombus.
In the present invention, the antithrombotic effect can be confirmed, for example, by measuring the activated partial thromboplastin time (APTT), which is a method for measuring the anticoagulant activity against the endogenous blood coagulation system.
本願発明の抗血栓組成物は、飲食品、医薬品、飼料等に応用でき、好ましくは、人が手軽に摂食できる飲食品が好ましい。
本願発明における飲食品とは溶液、懸濁物、粉末、固体成形物等経口摂取可能な形態であれば良く特に限定するものではない。より具体的には、即席麺、レトルト食品、缶詰、電子レンジ食品、即席スープ・みそ汁類、フリーズドライ食品等の即席食品類、清涼飲料、果汁飲料、野菜飲料、豆乳飲料、コーヒー飲料、茶飲料、粉末飲料、濃縮飲料、栄養飲料、アルコール飲料等の飲料類、パン、パスタ、麺、ケーキミックス、から揚げ粉、パン粉等の小麦粉製品、飴、キャラメル、チューイングガム、チョコレート、クッキー、ビスケット、ケーキ、パイ、スナック、クラッカー、和菓子、デザート菓子等の菓子類、ソース、トマト加工調味料、風味調味料、調理ミックス、たれ類、ドレッシング類、つゆ類、カレー・シチューの素類等の調味料、加工油脂、バター、マーガリン、マヨネーズ等の油脂類、乳飲料、ヨーグルト類、乳酸菌飲料、アイスクリーム類、クリーム類等の乳製品、冷凍食品、魚肉ハム・ソーセージ、水産練り製品等の水産加工品、畜肉ハム・ソーセージ等の畜産加工品、農産缶詰、ジャム・マーマレード類、漬け物、煮豆、シリアル等の農産加工品、栄養食品、錠剤、カプセル等が例示される。
The antithrombotic composition of the present invention can be applied to foods and drinks, pharmaceuticals, feeds, and the like, and preferably foods and drinks 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, Sweets such as pies, snacks, crackers, Japanese sweets, desserts, sauces, processed tomato seasonings, flavor seasonings, cooking mixes, sauces, dressings, soups, curry and stew seasonings, processing Fats and oils such as butter, margarine and mayonnaise, milk beverages, yogurts, lactic acid bacteria beverages, ice creams, chestnuts Agricultural processing such as dairy products such as mussels, frozen foods, processed fishery products such as fish meat ham and sausage, fish paste products, livestock processed products such as livestock ham and sausage, canned agricultural products, jams and marmalades, pickles, boiled beans and cereals Products, nutritional foods, tablets, capsules and the like.
本願発明において、抗血栓組成物又は、飲食品等に加工する際に、各種栄養成分を強化することができる。
強化できる栄養成分としては、ビタミンＡ、ビタミンＢ１、ビタミンＢ２、ビタミンＢ６、ビタミンＢ１２、ビタミンＣ、ビタミンＤ、ビタミンＥ、ナイアシン（ニコチン酸）、パントテン酸、葉酸等のビタミン類、リジン、スレオニン、トリプトファン等の必須アミノ酸類や、カルシウム、マグネシウム、鉄、亜鉛、銅等のミネラル類及び、例えば、α−リノレン酸、ＥＰＡ、ＤＨＡ、月見草油、オクタコサノール、カゼインホスホペプチド（ＣＰＰ）、カゼインカルシウムペプチド（ＣＣＰ）、水溶性食物繊維、不溶性食物繊維、オリゴ糖等の人の健康に寄与する物質類、その他の食品や食品添加物として認可されている有用物質の１種又は２種以上が使用できる。
In this invention, when processing into an antithrombotic composition or food-drinks etc., various nutrient components can be strengthened.
Nutritional ingredients that can be enhanced 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.
以下本発明を、実施例にて詳細に説明するが、次の実施例は、本発明の範囲を限定するものではない。 EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, the following Example does not limit the scope of the present invention.
（実施例１）抗血栓組成物の調製１
アムラー乾燥果実を４０メッシュ以下に粉砕し、その粉末８０グラムに、蒸溜水２リットルを入れ、５５℃で３時間抽出した。その後、遠心分離し、その上清を濾過し、抽出物と残渣を分離した。その残渣に蒸溜水２リットルを入れ、同条件でもう１回繰り返し抽出し、それぞれの抽出液をあわせて、本願発明の抗血栓組成物Ａを得た。
なお、得られた抽出液は固形分として７０．８ｇであり、収率は８８．５％であった。
Example 1 Preparation 1 of an antithrombotic composition
Amla dried fruits were crushed to 40 mesh or less, 2 liters of distilled water was added to 80 grams of the powder, and extracted at 55 ° C. for 3 hours. Then, it centrifuged and the supernatant was filtered and the extract and the residue were isolate | separated. 2 liters of distilled water was added to the residue, and extraction was repeated once again under the same conditions. The extracts were combined to obtain the antithrombotic composition A of the present invention.
In addition, the obtained extract was 70.8 g as solid content, and the yield was 88.5%.
（試験例１）抗血栓効果の確認
本願発明の抗血栓組成物の抗凝固活性を、人間の血液から分離した乏血小板血漿（Ｐｌａｔｅｌｅｔ Ｐｏｏｒ Ｐｌａｓｍａ，ＰＰＰ）を利用して凝固計（Ｃｏａｇｕｌｏｍｅｔｅｒ）で測定した。
反応キュベットに、試料１０マイクロリットル、ＡＰＴＴ試薬２５マイクロリットル、１０％セファリン２５マイクロリットルを入れて、３７℃で３分間反応させた後、ＰＰＰ５０マイクロリットルを入れて、２分間反応させた。最後に、２５ミリモル塩化カルシウム５０マイクロリットルを入れて、凝固させて、血漿が凝固されるまでの時間を測定し、ＡＰＴＴとした。
この時、対照に水を入れ、同じ方法でＡＰＴＴを測定した。測定された試料のＡＰＴＴから、下記の数式によって、対照に対する抗凝固活性（％）を計算した。
抗凝固活性（％）＝（（試料のＡＰＴＴ−対照のＡＰＴＴ）／対照のＡＰＴＴ）×１００
本願発明の抗血栓組成物Ａの濃度と、抗凝固活性との関係を確認するために、固形分濃度として、０（コントロール）、１、３、５ｍｇ／ｍｌの本願発明の抗血栓組成物を使用して、その活性を測定した。その結果を、下記表１に示す。
(Test Example 1) Confirmation of antithrombotic effect The anticoagulant activity of the antithrombotic composition of the present invention was measured with a coagulometer using platelet poor plasma (Platelet Poor Plasma, PPP) separated from human blood. did.
In a reaction cuvette, 10 microliters of sample, 25 microliters of APTT reagent, and 25 microliters of 10% Sephaline were added and reacted at 37 ° C. for 3 minutes, and then 50 microliters of PPP was added and reacted for 2 minutes. Finally, 50 microliters of 25 mM calcium chloride was added and allowed to clot, and the time until the plasma was clotted was measured and designated APTT.
At this time, water was added to the control and APTT was measured by the same method. The anticoagulant activity (%) relative to the control was calculated from the measured APTT of the sample by the following formula.
Anticoagulant activity (%) = ((sample APTT−control APTT) / control APTT) × 100
In order to confirm the relationship between the concentration of the antithrombotic composition A of the present invention and the anticoagulant activity, 0 (control), 1, 3, 5 mg / ml of the antithrombotic composition of the present invention was used as the solid content concentration. Used to measure its activity. The results are shown in Table 1 below.
表１
上記表１の結果により、本願発明の抗血栓組成物が高い抗凝固活性を示すことが確認できた。また抽出物の濃度を増加させることによって比例的に抗凝固活性も増加することが確認できた。 From the results in Table 1 above, it was confirmed that the antithrombotic composition of the present invention exhibits high anticoagulant activity. It was also confirmed that the anticoagulant activity increased proportionally by increasing the extract concentration.
（実施例２）抗血栓組成物の調製２
アムラー乾燥果実を４０メッシュ以下に粉砕し、その粉末８０グラムに、蒸溜水２リットルを入れ、５５℃で３時間抽出した。その後、遠心分離し、その上清を濾過し、抽出物と残渣を分離した。その残渣に蒸溜水２リットルを入れ、同条件でもう１回繰り返し抽出し、それぞれの抽出液をあわせて、減圧濃縮し、２００ミリリットルとした。この濃縮液にエタノールを加え、１リットルになるように調製（最終エタノール濃度８０％）した後、室温で２４時間静置して、不溶性成分を沈殿させた。沈澱物を、遠心分離で分離し、減圧乾燥後、水１リットルに再溶解し、濾過して不溶性成分除去後、濾液を凍結乾燥して本願発明の抗血栓組成物Ｂ３０．８ｇ（収率３８．５％）を得た。
(Example 2) Preparation 2 of antithrombotic composition
Amla dried fruits were crushed to 40 mesh or less, 2 liters of distilled water was added to 80 grams of the powder, and extracted at 55 ° C. for 3 hours. Then, it centrifuged and the supernatant was filtered and the extract and the residue were isolate | separated. Distilled water (2 liters) was added to the residue and extracted again under the same conditions. The extracts were combined and concentrated under reduced pressure to 200 ml. Ethanol was added to this concentrated solution to prepare 1 liter (final ethanol concentration 80%), and then allowed to stand at room temperature for 24 hours to precipitate insoluble components. The precipitate was separated by centrifugation, dried under reduced pressure, redissolved in 1 liter of water, filtered to remove insoluble components, and the filtrate was freeze-dried to obtain 30.8 g (yield 38) of the antithrombotic composition B of the present invention. .5%).
（試験例２）抗血栓効果の確認
実施例２で得られた抗血栓組成物Ｂについて、５ｍｇ／ｍｌの濃度で、ＡＰＴＴを測定した。その結果、ＡＰＴＴは、８５．１ｓｅｃであり、抗凝固活性は、８９．１％と、水抽出のみの抗血栓組成物Ａに比べて高い抗凝固活性を示すことが確認できた。
なお、実施例２において、エタノール可溶性成分についても同様にしてＡＰＴＴを測定した結果、ＡＰＴＴは、４８．０ｓｅｃであり、抗凝固活性は、６．７％であり、抗血栓活性画分はエタノールによる沈殿画分に含まれることがわかった。
(Test Example 2) Confirmation of antithrombotic effect The antithrombotic composition B obtained in Example 2 was measured for APTT at a concentration of 5 mg / ml. As a result, the APTT was 85.1 sec, and the anticoagulant activity was 89.1%, confirming that the anticoagulant activity was higher than that of the antithrombotic composition A obtained only by water extraction.
In Example 2, the APTT was measured in the same manner for ethanol-soluble components. As a result, APTT was 48.0 sec, anticoagulant activity was 6.7%, and the antithrombotic activity fraction was ethanol. It was found to be contained in the precipitate fraction.
（実施例３）抗血栓組成物含有食品（錠菓）の調製
実施例２で得られた抗血栓組成物Ｂ ５０ｇ、乳糖３０ｇ、ＤＨＡ含有粉末油脂（サンコートＤＹ−５；太陽化学株式会社製）１２ｇ、ショ糖脂肪酸エステル４ｇ、ヨーグルト香料４ｇを混合し、１錠が３００ｍｇになるように打錠して、本願発明の抗血栓組成物含有飲食品（錠菓）を得た。
(Example 3) Preparation of antithrombotic composition-containing food (tablet confectionery) 50 g of antithrombotic composition B obtained in Example 2, 30 g of lactose, 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 yogurt flavor were mixed, and tableted so that 1 tablet would be 300 mg to obtain a food / beverage product (tablet cake) containing the antithrombotic composition of the present invention.
（実施例４）抗血栓組成物含有飲料（野菜果汁混合飲料）の調製
実施例２で得られた抗血栓組成物Ｂ １ｇ及び、グアーガム分解物（サンファイバーＲ；太陽化学株式会社製）３ｇを市販の野菜果汁混合飲料１００ｍｌに添加混合溶解して、本願発明の抗血栓組成物含有飲食品（野菜果汁混合飲料）を得た。
(Example 4) Preparation of antithrombotic composition-containing beverage (vegetable juice mixed beverage) 1 g of antithrombotic composition B obtained in Example 2 and 3 g of guar gum degradation product (Sunfiber R; manufactured by Taiyo Chemical Co., Ltd.) It added, mixed and dissolved in 100 ml of commercially available vegetable juice mixed drinks, and the antithrombotic composition containing food / beverage products (vegetable fruit juice mixed drink) of this invention were obtained.
本発明の実施態様ならびに目的生成物を挙げれば以下の通りである。
（１） アムラーの果実、果汁又はそれらの抽出物を含有することを特徴とする抗血栓組成物。
（２） アムラー果実又は果汁の抽出物が、アムラー果実又は果汁から水、塩基、酸のいずれかにより抽出されていることを特徴とする前記（１）記載の抗血栓組成物。
（３） アムラー果実又は果汁の抽出物が、アムラー果実又は果汁から水により抽出されていることを特徴とする前記（１）又は（２）記載の抗血栓組成物。
（４） アムラー果実又は果汁の抽出物、又は果汁から、エタノールにより分画されていることを特徴とする前記（１）〜（３）いずれか記載の抗血栓組成物。
（５） アムラー果実又は果汁の抽出物、又は果汁から、エタノールにより沈殿物として分画されていることを特徴とする前記（１）〜（４）いずれか記載の抗血栓組成物。
（６） エタノールで分画する際のエタノール濃度が、終濃度として６０〜９５％であり、その沈殿画分であることを特徴とする前記（５）記載の抗血栓組成物。
（７） エタノールで分画する際のエタノール濃度が、終濃度として７０〜９０％であり、その沈殿画分であることを特徴とする前記（５）又は（６）記載の抗血栓組成物。
（８） 前記（１）〜（７）いずれか記載の抗血栓組成物を含有することを特徴とする飲食品。
（９） 前記（１）〜（７）いずれか記載の抗血栓組成物を含有することを特徴とする医薬品。
（１０） 前記（１）〜（７）いずれか記載の抗血栓組成物を含有することを特徴とする飼料。
The embodiment of the present invention and the target product are as follows.
(1) An antithrombotic composition comprising Amlar fruit, fruit juice, or an extract thereof.
(2) The antithrombotic composition according to the above (1), wherein the extract of Amler fruit or fruit juice is extracted from Amlar fruit or fruit juice with any of water, base, and acid.
(3) The antithrombotic composition as described in (1) or (2) above, wherein the extract of Amler fruit or fruit juice is extracted from Amlar fruit or fruit juice with water.
(4) The antithrombotic composition according to any one of (1) to (3), wherein the composition is fractionated with ethanol from an extract of Amler fruit or fruit juice, or fruit juice.
(5) The antithrombotic composition according to any one of (1) to (4), wherein the composition is fractionated as a precipitate with ethanol from an extract of Amler fruit or fruit juice, or fruit juice.
(6) The antithrombotic composition according to (5) above, wherein the ethanol concentration when fractionated with ethanol is 60 to 95% as a final concentration, and is a precipitate fraction thereof.
(7) The antithrombotic composition according to (5) or (6) above, wherein the ethanol concentration at the time of fractionation with ethanol is 70 to 90% as a final concentration, and is a precipitate fraction thereof.
(8) Food / beverage products characterized by including the antithrombotic composition in any one of said (1)-(7).
(9) A pharmaceutical comprising the antithrombotic composition according to any one of (1) to (7).
(10) A feed comprising the antithrombotic composition according to any one of (1) to (7).
本発明で得られたアムラー抽出物を含有するの抗血栓組成物は、血液凝固体系の内因性経路に関与する、多くの酵素と最終段階であるフィブリンを形成するトロンビンの活性を阻害し、血栓の生成を抑制する抗血栓効果が高く、各種飲食品及び医薬品等に利用して、血栓の生成を抑制することで脳出血、脳梗塞、心筋梗塞、動脈硬化及び冠状動脈症のような心血関係疾患を予防することができる。 The antithrombotic composition containing the Amler extract obtained in the present invention inhibits the activity of thrombin which forms fibrin which is the final stage with many enzymes involved in the intrinsic pathway of the blood coagulation system, and thrombus High anti-thrombotic effect that suppresses the formation of blood clots, and is used in various foods and medicines, etc. to suppress the formation of thrombus, thereby causing cardiovascular diseases such as cerebral hemorrhage, cerebral infarction, myocardial infarction, arteriosclerosis and coronary artery disease Can be prevented.
Claims (4)
Food-drinks characterized by including the antithrombotic composition in any one of Claims 1-3.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
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| JP2003405436A JP2005162684A (en) | 2003-12-04 | 2003-12-04 | Antithrombotic composition |
| CN 200480041388 CN1913909A (en) | 2003-12-04 | 2004-11-30 | Composition for inhibiting thrombosis |
| CA002547590A CA2547590A1 (en) | 2003-12-04 | 2004-11-30 | Composition for inhibiting thrombosis |
| EP04820510A EP1721533A4 (en) | 2003-12-04 | 2004-11-30 | Composition for inhibiting thrombosis |
| PCT/JP2004/017780 WO2005058339A1 (en) | 2003-12-04 | 2004-11-30 | Composition for inhibiting thrombosis |
| US10/581,287 US7914830B2 (en) | 2003-12-04 | 2004-11-30 | Composition for inhibiting thrombosis |
| TW093137554A TW200533365A (en) | 2003-12-04 | 2004-12-03 | Composition for inhibiting thrombosis |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003405436A JP2005162684A (en) | 2003-12-04 | 2003-12-04 | Antithrombotic composition |
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| JP2003405436A Pending JP2005162684A (en) | 2003-12-04 | 2003-12-04 | Antithrombotic composition |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005179250A (en) * | 2003-12-19 | 2005-07-07 | Taiyo Kagaku Co Ltd | Composition for inhibiting platelet aggregation |
| JP2006008529A (en) * | 2004-06-22 | 2006-01-12 | Taiyo Kagaku Co Ltd | Composition for inhibiting fibrin formation |
| WO2006106995A1 (en) * | 2005-03-31 | 2006-10-12 | Kobayashi Pharmaceutical Co., Ltd. | Matrix metalloproteinase inhibitor comprising ingredient extracted from amula |
| JP2007039386A (en) * | 2005-08-03 | 2007-02-15 | Taiyo Kagaku Co Ltd | Composition for regulating marker protein level, and food/drink, feed, quasi-drug and pharmaceutical each containing the composition |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101194725B (en) * | 2008-01-09 | 2011-04-06 | 北京市科威华食品工程技术有限公司 | Sargassum fusiforme nutrition health care beverage |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1278433A (en) * | 2000-04-26 | 2001-01-03 | 中国科学院昆明植物研究所 | Thrombolytic medicine and its preparation and use |
| US6290996B1 (en) * | 1999-02-17 | 2001-09-18 | Natreon Inc. | Method of inhibiting blood platelet aggregation |
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2003
- 2003-12-04 JP JP2003405436A patent/JP2005162684A/en active Pending
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6290996B1 (en) * | 1999-02-17 | 2001-09-18 | Natreon Inc. | Method of inhibiting blood platelet aggregation |
| CN1278433A (en) * | 2000-04-26 | 2001-01-03 | 中国科学院昆明植物研究所 | Thrombolytic medicine and its preparation and use |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005179250A (en) * | 2003-12-19 | 2005-07-07 | Taiyo Kagaku Co Ltd | Composition for inhibiting platelet aggregation |
| JP2006008529A (en) * | 2004-06-22 | 2006-01-12 | Taiyo Kagaku Co Ltd | Composition for inhibiting fibrin formation |
| WO2006106995A1 (en) * | 2005-03-31 | 2006-10-12 | Kobayashi Pharmaceutical Co., Ltd. | Matrix metalloproteinase inhibitor comprising ingredient extracted from amula |
| JP2007039386A (en) * | 2005-08-03 | 2007-02-15 | Taiyo Kagaku Co Ltd | Composition for regulating marker protein level, and food/drink, feed, quasi-drug and pharmaceutical each containing the composition |
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| CN1913909A (en) | 2007-02-14 |
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