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    Hirudin analogs, methods of manufacture thereof and anticoagulant compositions having these as active ingredients
    1.
    发明授权
    Hirudin analogs, methods of manufacture thereof and anticoagulant compositions having these as active ingredients 失效
    水蛭素类似物，其制造方法和具有这些作为活性成分的抗凝血剂组合物

    公开(公告)号：US5972648A

    公开(公告)日：1999-10-26

    申请号：US861459

    申请日：1997-05-22

    申请人： Akiko Sukesada ,  Satoru Misawa ,  Hitoshi Matsuda

    发明人： Akiko Sukesada ,  Satoru Misawa ,  Hitoshi Matsuda

    IPC分类号： A61K38/00 ,  C07K14/815 ,  C12N15/12 ,  C07H21/04 ,  C07K14/00 ,  C12N15/63

    CPC分类号： C07K14/815 ,  A61K38/00

    摘要： Disclosed are hirudin analogs, a method of manufacture thereof, and anticoagulant compositions containing the same. Sequences Asp.sup.33 -Gly.sup.34 or Asp.sup.62 -Ala.sup.63 of naturally-occurring hirudins or their analogs were substituted as disclosed to suppress the formation of succinimide- or beta- forms, thereby yielding hirudin analogs with high stability, high anti-thrombin activity, and therapeutic potential as anticoagulants. Hirudin analogs having Val.sup.1 -Val.sup.2 of naturally-occurring hirudin substituted with Ile.sup.1 -Ile.sup.2 are preferred for their high antithrombiin activity. The invention also provides DNAs encoding the amino acid sequence of hirudin analogs, expression vectors, recombinant microogranisms, and a method of manufacturing hirudin analogs using recombinant microorganisms.

    摘要翻译： 公开了水蛭素类似物，其制造方法和含有该水溶液的抗凝剂组合物。 天然存在的水蛭素或其类似物的序列Asp33-Gly34或Asp62-Ala63被公开地取代以抑制琥珀酰亚胺或β-形成，由此产生具有高稳定性，高抗凝血酶活性和治疗潜力的水蛭素类似物 抗凝剂 由于其抗血小板活性高，因此优选具有被Ile1-Ile2取代的天然水蛭素的Val1-Val2的水蛭素类似物。 本发明还提供编码水蛭素类似物，表达载体，重组微粒体的氨基酸序列的DNA，以及使用重组微生物制备水蛭素类似物的方法。

    Anticoagulant hirudin variants and methods for their production
    2.
    发明授权
    Anticoagulant hirudin variants and methods for their production 失效
    抗凝血水蛭素变体及其生产方法

    公开(公告)号：US5767235A

    公开(公告)日：1998-06-16

    申请号：US367758

    申请日：1995-01-03

    申请人： Eriko Nukui ,  Koichi Wada ,  Masaharu Nakano ,  Tadanori Morikawa ,  Kyoichi Kobashi ,  Ryo Muramatsu ,  Akiko Sukesada ,  Satoru Misawa

    发明人： Eriko Nukui ,  Koichi Wada ,  Masaharu Nakano ,  Tadanori Morikawa ,  Kyoichi Kobashi ,  Ryo Muramatsu ,  Akiko Sukesada ,  Satoru Misawa

    IPC分类号： A61K38/00 ,  C07K14/815 ,  A61K38/08

    CPC分类号： C07K14/815 ,  A61K38/00

    摘要： The present invention relates to hirudin variants having high anti-thrombin and anti-platelet activity, methods for producing them, and anti-coagulants having said variants as active ingredients. Hirudin variants shown in formula (I) having tyrosine residues or having their hydroxyl group sulfated. Methods for producing hirudin variants by sulfating hydroxyl group of said tyrosine residues, and anti-coagulants having hirudin variants shown in formula (I) as active ingredients. Phe-Glu-A-Ile-Pro-B-Tyr(R)-Tyr(R) (I) �In the formula, A represents Glu or Pro, B represents Glu, Tyr (R), Glu-Asp or Glu-Tyr(R), and (R) represents the hydroxy group or its sulfated ester (--O--SO.sub.3 H) of tyrosine residue.!

    摘要翻译： 本发明涉及具有高抗凝血酶和抗血小板活性的水蛭素变体，其制备方法和具有所述变体作为活性成分的抗凝血剂。 具有酪氨酸残基或其羟基硫酸化的式（I）所示的水蛭素变体。 通过将所述酪氨酸残基的羟基硫酸化制备水蛭变体的方法和具有式（I）所示水蛭素变体的抗凝血剂作为活性成分。Phe-Glu-A-Ile-Pro-B-Tyr（R）-Tyr R）（I）[式中，A表示Glu或Pro，B表示Glu，Tyr（R），Glu-Asp或Glu-Tyr（R），（R）表示羟基或其硫酸酯（ - O-SO3H）酪氨酸残基。

    Anticoagulant hirudin variants and methods for their production
    3.
    发明授权
    Anticoagulant hirudin variants and methods for their production 失效
    抗凝血水蛭素变体及其生产方法

    公开(公告)号：US5880258A

    公开(公告)日：1999-03-09

    申请号：US909735

    申请日：1997-08-12

    申请人： Ryo Muramatsu ,  Akiko Sukesada ,  Satoru Misawa ,  Eriko Nukui ,  Koichi Wada ,  Masaharu Nakano ,  Tadanori Morikawa ,  Kyoichi Kobashi

    发明人： Ryo Muramatsu ,  Akiko Sukesada ,  Satoru Misawa ,  Eriko Nukui ,  Koichi Wada ,  Masaharu Nakano ,  Tadanori Morikawa ,  Kyoichi Kobashi

    IPC分类号： A61K38/00 ,  C07K14/815 ,  C07K14/00

    CPC分类号： C07K14/815 ,  A61K38/00

    摘要： The present invention relates to hirudin variants having high anti-thrombin and anti-platelet activity, methods for producing them, and anti-coagulants having said variants as active ingredients.Hirudin variants shown in formula (I) having tyrosine residues or having their hydroxyl group sulfated.Methods for producing hirudin variants by sulfating hydroxyl group of said tyrosine residues, and anti-coagulants having hirudin variants shown in formula (I) as active ingredients.Phe-Glu-A-Ile-Pro-D-Tyr(R) Tyr(R) (I)�In the formula, A represents Glu or Pro, R represents Glu, Tyr (R), Glu-Asp or Glu-Tyr(R), and (R) represents the hydroxy group or its sulfated ester (--O--SO.sub.3 H) of tyrosine residue.!

    摘要翻译： 本发明涉及具有高抗凝血酶和抗血小板活性的水蛭素变体，其制备方法和具有所述变体作为活性成分的抗凝血剂。 具有酪氨酸残基或其羟基硫酸化的式（I）所示的水蛭素变体。 通过硫酸化所述酪氨酸残基的羟基来生产水蛭变异体的方法和具有式（I）所示的水蛭素变体的抗凝血剂作为活性成分。Phe-Glu-A-Ile-Pro-D-Tyr（R）Tyr ）（I）[式中，A表示Glu或Pro，R表示Glu，Tyr（R），Glu-Asp或Glu-Tyr（R），（R）表示羟基或其硫酸酯 -SO3H）酪氨酸残基。