JPS6323819A - Inhibitor of blood platelet aggregation - Google Patents
Inhibitor of blood platelet aggregationInfo
- Publication number
- JPS6323819A JPS6323819A JP16754086A JP16754086A JPS6323819A JP S6323819 A JPS6323819 A JP S6323819A JP 16754086 A JP16754086 A JP 16754086A JP 16754086 A JP16754086 A JP 16754086A JP S6323819 A JPS6323819 A JP S6323819A
- Authority
- JP
- Japan
- Prior art keywords
- extract
- krill
- platelet aggregation
- organic solvent
- inhibitor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 208000010110 spontaneous platelet aggregation Diseases 0.000 title abstract description 12
- 239000003112 inhibitor Substances 0.000 title abstract 4
- 210000001772 blood platelet Anatomy 0.000 title abstract 2
- 239000000284 extract Substances 0.000 claims abstract description 28
- 241000239366 Euphausiacea Species 0.000 claims abstract description 24
- 150000003904 phospholipids Chemical class 0.000 claims abstract description 20
- 239000003960 organic solvent Substances 0.000 claims abstract description 19
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- 229940127218 antiplatelet drug Drugs 0.000 claims description 13
- 239000000106 platelet aggregation inhibitor Substances 0.000 claims description 13
- 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 claims description 12
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 claims description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract description 6
- 238000003756 stirring Methods 0.000 abstract description 5
- 238000001914 filtration Methods 0.000 abstract description 2
- 208000024891 symptom Diseases 0.000 abstract description 2
- 208000007536 Thrombosis Diseases 0.000 description 6
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 239000002026 chloroform extract Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000239368 Euphausia Species 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000012503 blood component Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
- 229960005135 eicosapentaenoic acid Drugs 0.000 description 2
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 2
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 241001454420 Recurva Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000324401 Superba Species 0.000 description 1
- 239000004784 Superba Substances 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- -1 phenylbutacin Chemical compound 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は血小板凝集抑制剤に関し、更に詳細にはオキア
ミヲ有機溶剤で抽出することにより得られる副作用が少
なく安定性の高い血小板凝集抑制剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a platelet aggregation inhibitor, and more particularly to a platelet aggregation inhibitor with few side effects and high stability obtained by extracting krill with an organic solvent.
血管内に血栓が形成されると血流が著しく阻害され、組
織に重大な障害をもたらすことが知られている。この血
栓形成による疾患、すなわち、血栓症の病態生理におい
て、血栓形成因子として血管壁の性状、血流速度及び血
液成分の三つの因子が挙げられ、これらは互いに影響し
あい重要な役割を果していることが知られている。この
うち、血液成分の１つである血小板の役割は非常に重要
であり、血小板の凝集亢進により血栓症の誘発の可能性
が実験的に、また疫学的に証明されている。It is known that the formation of a thrombus within a blood vessel significantly impedes blood flow and causes serious damage to tissues. In the pathophysiology of this disease caused by thrombus formation, that is, thrombosis, there are three factors that can be cited as thrombus forming factors: the properties of the blood vessel wall, blood flow velocity, and blood components, and these factors interact with each other and play important roles. It has been known. Among these, the role of platelets, which are one of the blood components, is very important, and it has been experimentally and epidemiologically proven that thrombosis may be induced by enhanced aggregation of platelets.
さらに最近、動脈硬化症の発症メカニズムの解明に従い
、動脈硬化症の発症第一段階が損傷血管内皮細胞への血
小板凝集であることが明らかとなってきた。そこで近年
血栓症の治療・予防のため、抗血小板凝集剤であるアス
ピリン、インドメサシン、フェニルブタシン、クロフィ
ブレート、デキストランサルフェート１．Ｑ、Ｑベリン
、へ、Ｑリン等の薬剤、あるいはエイコサペンタエン酸
等の高度不飽和脂肪酸の、経口的もしくは静脈注射によ
る投与がおこなわれている。Furthermore, as the mechanism of onset of arteriosclerosis has recently been elucidated, it has become clear that the first step in the onset of arteriosclerosis is platelet aggregation on damaged vascular endothelial cells. Therefore, in recent years, anti-platelet aggregation agents such as aspirin, indomethacin, phenylbutacin, clofibrate, and dextran sulfate have been used to treat and prevent thrombosis. Drugs such as Q, Qberin, He, Qlin, and polyunsaturated fatty acids such as eicosapentaenoic acid are administered orally or by intravenous injection.
しかしながら、上記薬剤はいずれも副作用、薬効、安定
性のいずれかの面において十分に満足し得るものでなく
、これらに代る、副作用がなく、薬効、安定性の面でも
優れた血小板凝集抑制剤の開発が望まれていた。また、
日常的に投与可能とするために、当該血小板凝集抑制剤
は経口投与できるものであることが望まれていた。However, none of the above drugs is fully satisfactory in terms of side effects, efficacy, or stability, and there are no alternative platelet aggregation inhibitors that have no side effects and are excellent in efficacy and stability. development was desired. Also,
It has been desired that the platelet aggregation inhibitor can be administered orally in order to be able to be administered on a daily basis.
このような実情に鑑み、本発明者らは上記要望を満足す
る血小板凝集抑制剤を得べく鋭意研究をおこなった結果
、オキアミの有機溶剤抽出物は優れた血小板凝集抑制作
用を有すること及びこのものは副作用が少なく、安定性
も優れ、しかも経口投与できることを見出し、本発明を
完成した。In view of these circumstances, the present inventors conducted intensive research to obtain a platelet aggregation inhibitor that satisfies the above requirements, and as a result, it was found that an organic solvent extract of krill has an excellent platelet aggregation inhibitory effect and that this product has an excellent platelet aggregation inhibitory effect. The present invention was completed based on the discovery that the compound has few side effects, excellent stability, and can be administered orally.
したがって本発明はオキアミの有機溶剤抽出物を有効成
分として含有する血小板凝集抑制剤を提供するものであ
る。Therefore, the present invention provides a platelet aggregation inhibitor containing an organic solvent extract of krill as an active ingredient.
本発明で使用するオキアミとしては、例えば１ス、ｅ−
パ（５ｕｐｅｒｂａ ）、クリスｐ ｏ ｏ ７ イア
ス（ｃｒｙｓｔａｌｌｏ ｒｏｐｈｉａｓ ）、フリシ
ダ（ｆｒｉｇｉｄａ）、トリアカメサ（ｔｒｉａｃａｎ
ｔｈａ ）％ ベランテイニ（Ｖｅｌｌａｎｔｉｎｉ
）、ｏ−ゾロストリス（ｌｏｕｇｉｒｏｓｔｒｉｓ）、
ルーセンス（１ｕｃｅｎｓ ）、シミリス（５１ｍ１
ｌ ｉｓ ）、スビニフエラ（５ｐｉｎｉｆｅｒａ ）
、レクルバ（ｒｅｃｕｒｖａ ）等のオイファウシア（
Ｅｕｐｈａｕｓｉａ ）属、マカルーラ（ｍａｃａｒｕ
ｒａ ） ｓビシナ（Ｖｉｃｉｎａ）、ブレグリア（ｇ
ｒｅｇａｒｉａ ）等のシサノエシサ（Ｔｈｙｓａｎｏ
ｅｓｓａ ）属等のいずれでも使用可能であって、特別
な種類に限定でれない。Examples of krill used in the present invention include 1st, e-
5uperba, crystallo rophias, frigida, triacan
tha )% Bellantini
), o-zorostris,
Lucens (1ucens), Similis (51m1
l is ), Subinifera (5pinifera)
, Oifausia (recurva) etc.
Euphausia ) genus, macaru
ra) s Vicina, Breglia (g
regaria) etc.
Any of the genus essa ) can be used, and it is not limited to a particular type.
なお、原料であるこのオキアミは全世界の海洋に分布し
、特に南極周辺に多く、生息量は数億トン〜２０億トン
といわれており、現在の全世界漁獲量に匹敵する５００
０〜７０００万トン／年の漁獲も可能と考えられている
もので、原料供給の面でも安定供給が可能である０
このオキアミの有機溶剤による抽出は常法によりおこな
われる。例えばオキアミ若しくはその粉砕物をクロロホ
ルム、ベンゼン、ブタノール、エーテル等の非極性溶剤
又はクロロホルム−メタノール、エーテル−エタノール
、ブタノール−水等の非極性溶剤と極性溶剤の混液等の
有機溶剤中に投入し、好ましくは１５〜６０℃で２〜２
４時間攪拌し、濾過することによりおこなわれる。有機
溶剤のうち、特に好ましいものとしては、クロロホルム
、クロロホルム−メタノール及びブタノール−水が挙げ
られる。The raw material, krill, is distributed throughout the world's oceans, and is particularly abundant around Antarctica, with an estimated population of hundreds of millions to 2 billion tons, which is equivalent to the current global catch of 500 million tons.
It is thought that it is possible to catch 0 to 70 million tons per year, and a stable supply of raw materials is possible.0 This extraction of krill with an organic solvent is carried out by a conventional method. For example, krill or its pulverized product is placed in a non-polar solvent such as chloroform, benzene, butanol, or ether, or an organic solvent such as a mixture of a non-polar solvent and a polar solvent such as chloroform-methanol, ether-ethanol, or butanol-water, Preferably 2 to 2 at 15 to 60°C
This is done by stirring for 4 hours and filtering. Particularly preferred organic solvents include chloroform, chloroform-methanol, and butanol-water.
このようにして得られたオキアミの有機溶剤抽出物は、
これをそのまま、あるいは濃縮若しくは乾燥して血小板
凝集抑制剤として用いることもできるが、更に該抽出物
からリン脂質画分を取り出し、用いることもできる。The organic solvent extract of krill obtained in this way is
This can be used as it is or after being concentrated or dried as a platelet aggregation inhibitor, but it is also possible to take out the phospholipid fraction from the extract and use it.
リン脂質画分を取り出す方法としては、例えば上記抽出
物を濃縮した後、大量の冷アセトン中に小量ずつ滴下し
てリン脂質画分を沈澱させる方法及び薄層クロマトグラ
フィー等により分離・採取する方法が例示される。The phospholipid fraction can be extracted by, for example, concentrating the above extract and then dropping it into a large amount of cold acetone to precipitate the phospholipid fraction, or separating and collecting it by thin layer chromatography, etc. A method is illustrated.
本発明の血小板凝集抑制剤は、叙上の如くして得られた
オキアミの有機溶剤抽出物又はこれから得られたリン脂
質画分を必要に応じて公知の医薬用担体と配合すること
により製造される。なお、オキアミの有機溶剤抽出物を
用いる場合、抽出物中の有機溶剤は水と置換させ、除去
することが好ましい。The platelet aggregation inhibitor of the present invention is produced by blending the organic solvent extract of krill obtained as described above or the phospholipid fraction obtained therefrom with a known pharmaceutical carrier as necessary. Ru. In addition, when using an organic solvent extract of krill, it is preferable to replace the organic solvent in the extract with water and remove it.
斯くして得られた本発明の血小板凝集抑制剤は、成人男
子に対し、抽出物もしくはリン脂質画分中のリン脂質量
として１〜２０ｒ／日程度経口投与することが好ましい
が、症状の程度によっては更に投与量？増やすことも可
能である。The thus obtained platelet aggregation inhibitor of the present invention is preferably orally administered to adult males in an amount of phospholipids in the extract or phospholipid fraction of about 1 to 20 r/day, but depending on the severity of symptoms. Depending on the dosage? It is also possible to increase it.
なお、本発明の血小板凝集抑制剤の有効成分である抽出
物及びリン脂質画分は、これらに含まれるリン脂質のラ
ットに対するＬＤｓ。Note that the extract and phospholipid fraction, which are the active ingredients of the platelet aggregation inhibitor of the present invention, have LDs for rats of the phospholipids contained therein.
（経口）が２５５’／ＫＰであることかられかるように
極めて安全性の高いものである。(oral) is 255'/KP, so it is extremely safe.
〔作用〕
本発明のオキアミ有機溶剤抽出物の血小板凝集抑制作用
の機作は詳細には解明でれていないがオキアミ有機溶剤
抽出物に含有されるエイコサペンタエン酸等の高度不飽
和脂肪酸を多量に有するリン脂質に由来するものと考え
られる。[Effect] Although the mechanism of the platelet aggregation inhibiting effect of the organic solvent extract of krill of the present invention has not been elucidated in detail, the organic solvent extract of krill contains a large amount of highly unsaturated fatty acids such as eicosapentaenoic acid. It is thought that it originates from the phospholipid that it has.
叙上の如く、本発明のオキアミ有機溶剤抽出物及び、特
にこれから導かれるリン脂質画分は経口投与にて優れた
血小板凝集抑制作用を示し、しかも毒性・副作用もない
ので極めて優れた血小板凝集抑制剤である。As mentioned above, the organic solvent extract of krill of the present invention, and especially the phospholipid fraction derived therefrom, exhibits excellent platelet aggregation inhibitory effects when administered orally, and has no toxicity or side effects, so it is an extremely excellent platelet aggregation inhibitor. It is a drug.
以下に実施例金あげて本発明？更に具体的に説明する。 Is this invention given below as an example? This will be explained more specifically.
実施例１゜
凍結乾燥されたオキアミ〔オイファウシア０スノ９−バ
（Ｅｕｐｈａｕｓｉａ ５ｕｐｅｒｂａ ） ’Ｊ ’
ｒ細かく砕き、この粉砕物５００２にブタノール−水（
６５：３５）混液シ０００−を加え、５０℃で２０時間
、攪拌させながら脂質全抽出し、戸別することによりブ
タノール−水抽出液を得た０
戸別したブタノール−水抽出液全減圧濃縮し、ブタノー
ルを除去後、きらにｄａＬ、てブタノール−水抽出液４
０２（水含量２８ｖ）を得た。Example 1 Freeze-dried krill (Euphausia 5uperba) 'J'
r Finely crushed, and this crushed material 5002 is mixed with butanol-water (
65:35) Add the mixed liquid Shi000-, and completely extract the lipids while stirring at 50°C for 20 hours, and separate the butanol-water extract to obtain a butanol-water extract. After removing butanol, use Kirani daL, butanol-water extract 4
02 (water content 28v) was obtained.
実施例２゜
（１） 凍結乾燥されたオキアミ〔オイファウシア・
スパーバ（Ｅｕｐｈａｕｓｉａ ５ｕｐｅｒｂａ ）
〕ｆ細かく砕き、この粉砕物５００２に１０００−のク
ロロホルムを加え、４０℃で２０時間、攪拌をせながら
脂質を抽出し、戸別することによりクロロホルム抽出液
を得た。Example 2゜(1) Freeze-dried krill [Oifausia
Superba (Euphausia 5upperba)
[f] The pulverized product 5002 was crushed with 1000 ml of chloroform, and the lipids were extracted with stirring at 40° C. for 20 hours, and the mixture was distributed from house to house to obtain a chloroform extract.
（ＩＩ） 戸別したクロロホルム抽出液を減圧濃縮し
、乾固した後、水−エタノール（１：１）溶液を５０−
添加し、乾固物質を溶解させ、再度減圧濃縮しエタノー
ルを除去し、オキアミクロロホルム抽出物３７２（水含
［２５ｔ）’を得た０
実施例３゜
実施例２．（１）と同様にして調製したクロロホルム抽
出液を約１０．／となるまで減圧濃縮した後、２０００
−のアセトンの中へ攪拌させながら滴下し、リン脂質画
分を沈澱させた。沈澱物を減圧濾過し採散じた後、水−
エタノールｌ：１の混合浴液３０１ｎｔに溶解し、減圧
濃ＭＫよりエタノールを除去した。オキアミのクロロホ
ルム抽出物のリン脂質画分２０？（水含量１５ｆ）が得
られた。(II) After concentrating the chloroform extracts from each household under reduced pressure and drying them, a water-ethanol (1:1) solution was diluted with 50-
Example 3 Example 2. The chloroform extract prepared in the same manner as in (1) was added for about 10 minutes. After concentrating under reduced pressure until /, 2000
- was added dropwise into acetone with stirring to precipitate the phospholipid fraction. After collecting the precipitate by vacuum filtration, water
It was dissolved in 301 nt of a mixed bath solution of 1:1 ethanol, and the ethanol was removed from concentrated MK under reduced pressure. Phospholipid fraction of krill chloroform extract 20? (Water content: 15 f) was obtained.
実施例４４
実施例１．実施例２．及び実施例３．で得たオキアミ抽
出物及びそのリン脂質画分について、それらの血小板凝
集抑制作用を試験した。すなわち％ １群１０匹のウィ
スター系雄ラット（体重２００ｆ）にゾンデを用いオキ
アミ抽出物及びリン脂質画分をそれぞれ０．５−ずつ２
週間毎日胃内投与した。実験最終日にネンプタール麻酔
下腹部大動脈より３．８％のクエン酸ナトリウム液をｌ
／ＩＯ量加え採血した。採血した血液は５ｏａｒ、２２
℃で６分間遠心して上清をＰＲＰ（Ｐｌａｔｅｌｅｔ
Ｒｉｃｈ ｐｌａｓｍａ ） とした。Example 44 Example 1. Example 2. and Example 3. The obtained krill extract and its phospholipid fraction were tested for their platelet aggregation inhibitory effects. In other words, % krill extract and phospholipid fraction were added to each group of 10 male Wistar rats (body weight 200 f) using a sonde at a rate of 0.5-2.
It was administered intragastrically every day for a week. On the final day of the experiment, 3.8% sodium citrate solution was administered from the abdominal aorta under Nemptal anesthesia.
/IO amount was added and blood was collected. The collected blood was 5 oar, 22
Centrifuge at ℃ for 6 minutes and transfer the supernatant to PRP (Platelet).
Rich plasma).
残りの血液を１０００ｆ、２２℃で１５分間遠心して上
溝を乏血小板血漿（Ｐｌａｔｅｌｅｔ Ｐｏｏｒｐｌａ
ｓｍａ 、 ＰＰＰ）とした。血小板凝集能はエルマ社
製アグリテツクＴＥ−５００ｔ−用いて測定し、最大凝
集率及び最大凝集時間で示し次。なお、血小板凝集能は
血小板数がＰＲＰ ２００μＥ中５〜７ Ｘ １０’個
となるようにＰＰＰで稀釈し、凝集惹起物質としてＡＤ
Ｐ ２０μｍｏｌ生理食塩水溶液２０μＡ′を添加した
。また、対照群としては、水のみ投与したラットを用い
た。この結果を第１表に示す。The remaining blood was centrifuged at 1000f and 22°C for 15 minutes, and the upper groove was collected with platelet poor plasma (Platelet Poor Plasma).
sma, PPP). Platelet aggregation ability was measured using Agritech TE-500t manufactured by Elma, and was expressed as the maximum aggregation rate and maximum aggregation time. In addition, platelet aggregation ability was determined by diluting platelets with PPP so that the number of platelets was 5 to 7 x 10' in 200 μE of PRP, and using AD as an aggregation-inducing substance.
20 μA' of a 20 μmol P saline solution was added. In addition, as a control group, rats to which only water was administered were used. The results are shown in Table 1.
以上の結果からオキアミ有機溶媒抽出物特にそのリン脂
質画分は血小板凝集抑制作用を有することが明らかとな
った。From the above results, it has become clear that the organic solvent extract of krill, particularly its phospholipid fraction, has an inhibitory effect on platelet aggregation.
裂剤例
組成：
■オ♀アミリン脂質’ １００哩
■乳 ｍ ＺＯＯ押
■ケイ酸アル電ニウム ５０１１？
■ステアリン酸マグネシウム ５１１ｇ＊完全に
抽出溶剤を除去した粉末物（実施例２．〕製法：
■〜■を混合し、打錠する。Composition of cleaving agent example: ■O♀Amyphospholipid' 100 m ■Milk ZOOpress■Alelectronium silicate 5011? (2) Magnesium stearate 511 g *Powder from which extraction solvent has been completely removed (Example 2.) Manufacturing method: (1) to (2) are mixed and tableted.
以上that's all
Claims (1)
る血小板凝集抑制剤。 ２、オキアミの有機溶剤抽出物がリン脂質画分である特
許請求の範囲第１項記載の血小板凝集抑制剤。[Scope of Claims] 1. A platelet aggregation inhibitor containing an organic solvent extract of krill as an active ingredient. 2. The platelet aggregation inhibitor according to claim 1, wherein the organic solvent extract of krill is a phospholipid fraction.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16754086A JPS6323819A (en) | 1986-07-16 | 1986-07-16 | Inhibitor of blood platelet aggregation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16754086A JPS6323819A (en) | 1986-07-16 | 1986-07-16 | Inhibitor of blood platelet aggregation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6323819A true JPS6323819A (en) | 1988-02-01 |
Family
ID=15851595
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16754086A Pending JPS6323819A (en) | 1986-07-16 | 1986-07-16 | Inhibitor of blood platelet aggregation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6323819A (en) |
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|---|---|---|---|---|
| WO2007080515A1 (en) * | 2006-01-13 | 2007-07-19 | Aker Biomarine Asa | Thrombosis preventing krill extract |
| JP2008239500A (en) * | 2007-03-25 | 2008-10-09 | Nippon Suisan Kaisha Ltd | Leptin secretion promoter |
| US8586567B2 (en) | 2009-10-29 | 2013-11-19 | Acasti Pharma, Inc. | Concentrated therapeutic phospholipid compositions |
| US8680080B2 (en) | 2001-07-27 | 2014-03-25 | Neptune Technologies & Bioressources, Inc. | Natural marine source phospholipids comprising polyunsaturated fatty acids and their applications |
| WO2014207571A3 (en) * | 2013-06-14 | 2015-04-30 | Aker Biomarine Antarctic As | Lipid extraction processes |
| US9320765B2 (en) | 2007-03-28 | 2016-04-26 | Aker Biomarine Antarctic As | Bioeffective krill oil compositions |
-
1986
- 1986-07-16 JP JP16754086A patent/JPS6323819A/en active Pending
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8680080B2 (en) | 2001-07-27 | 2014-03-25 | Neptune Technologies & Bioressources, Inc. | Natural marine source phospholipids comprising polyunsaturated fatty acids and their applications |
| WO2007080515A1 (en) * | 2006-01-13 | 2007-07-19 | Aker Biomarine Asa | Thrombosis preventing krill extract |
| JP2008239500A (en) * | 2007-03-25 | 2008-10-09 | Nippon Suisan Kaisha Ltd | Leptin secretion promoter |
| US10543237B2 (en) | 2007-03-28 | 2020-01-28 | Aker Biomarine Antarctic As | Bioeffective krill oil compositions |
| US10010567B2 (en) | 2007-03-28 | 2018-07-03 | Aker Biomarine Antarctic As | Bioeffective krill oil compositions |
| US9320765B2 (en) | 2007-03-28 | 2016-04-26 | Aker Biomarine Antarctic As | Bioeffective krill oil compositions |
| US9375453B2 (en) | 2007-03-28 | 2016-06-28 | Aker Biomarine Antarctic As | Methods for producing bioeffective krill oil compositions |
| US11865143B2 (en) | 2007-03-28 | 2024-01-09 | Aker Biomarine Antarctic As | Bioeffective krill oil compositions |
| US9816046B2 (en) | 2007-03-28 | 2017-11-14 | Aker Biomarine Antarctic As | Bioeffective krill oil compositions |
| US9889163B2 (en) | 2007-03-28 | 2018-02-13 | Aker Biomarine Antarctic As | Bioeffective krill oil compositions |
| US9475830B2 (en) | 2009-10-29 | 2016-10-25 | Acasti Pharma Inc. | Concentrated therapeutic phospholipid compositions |
| US10130644B2 (en) | 2009-10-29 | 2018-11-20 | Acasti Pharma Inc. | Concentrated therapeutic phospholipid compositions |
| US8586567B2 (en) | 2009-10-29 | 2013-11-19 | Acasti Pharma, Inc. | Concentrated therapeutic phospholipid compositions |
| US10617702B2 (en) | 2009-10-29 | 2020-04-14 | Acasti Pharma Inc. | Concentrated therapeutic phospholipid compositions |
| US10704011B2 (en) | 2013-06-14 | 2020-07-07 | Aker Biomarine Antarctic As | Lipid extraction processes |
| US11578289B2 (en) | 2013-06-14 | 2023-02-14 | Aker Biomarine Antarctic As | Lipid extraction processes |
| WO2014207571A3 (en) * | 2013-06-14 | 2015-04-30 | Aker Biomarine Antarctic As | Lipid extraction processes |
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