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    New anticoagulant hirudin-polyvinyl lactam conjugates - for treating e.g. myocardial infarction, peripheral arterial occlusion disorders, deep venous thrombosis and pulmonary embolism
    11.
    发明专利
    New anticoagulant hirudin-polyvinyl lactam conjugates - for treating e.g. myocardial infarction, peripheral arterial occlusion disorders, deep venous thrombosis and pulmonary embolism 未知

    公开(公告)号：DE4011375A1

    公开(公告)日：1991-10-10

    申请号：DE4011375

    申请日：1990-04-07

    Applicant: BASF AG

    Inventor： KURFUERST MANFRED DR ,  SCHMIED BERNHARD DR ,  RUEBSAMEN KLAUS DR ,  BLANKENBURG RAINER DR

    IPC: A61K38/00 ,  C07K14/815

    Abstract: Conjugates of formula (I), made from polyvinyl lactams and hirudin, desulphatohirudin or coagulation-inhibiting hirudin muteins are new. A = H, OH or CH3. n = 2-4; m = 50-500. B = -CO-, -CH=, -CH2-, -CH2-X-CO-, -CH2-X-Z-CO-, -CH2-X-CO-NH-Z-NH-CO-, -CH2-X-CH2-(1,4-Ph)-N2-, -CH2-X-CH2-CH(OH)-CH2-(1,4-Ph)-N2-, -CH2-X-CO-CH2-CH2-CO or -CH2-X-(4-W-(1,3,5-triazin-2,6-yl)). X = -S-, -O-, -NH-, -N(CH3)- or -N(C2H5)-. Z = 1-6C alkylene or p-phenylene. W = H, Cl or OH. Hir = the hirudin, desulphatohirudin or hirudin mutein, which is bound to B via the serine, threonine or lysine side chain(s). USE/ADVANTAGE - For the treatment and prevention of thromboembolic disorders (e.g. myocardial infarction), peripheral arterial occlusion disorders, deep venous thrombosis and pulmonary embolism. (I) can be used to prevent reocclusion after re-opening of arterial blood vessels by mechanical methods of lysis. Administration is i.v. or i.m. (I) have longer in vivo half life (1-100 hours) than hirudin alone (50 minutes) or even than hirudin-dextran conjugates (7 hours).

    New hirudin-poly:alkylene glycol conjugate(s) - used as anticoagulants for treatment and prophylaxis of myocardial infarct, arterial occlusion, venous thrombosis and pulmonary embolism
    18.
    发明专利
    New hirudin-poly:alkylene glycol conjugate(s) - used as anticoagulants for treatment and prophylaxis of myocardial infarct, arterial occlusion, venous thrombosis and pulmonary embolism 未知

    公开(公告)号：DE4014260A1

    公开(公告)日：1991-06-06

    申请号：DE4014260

    申请日：1990-05-04

    Applicant: BASF AG

    Inventor： KURFUERST MANFRED DR ,  RUEBSAMEN KLAUS DR ,  SCHMIED BERNHARD DR

    IPC: A61K38/00 ,  A61K47/48 ,  C07K14/815

    Abstract: Hirudin-polyalkylene glycol conjugates (I) (A-(CH2)n-(O-(CH2)n)m-B-)pHir are new. In (I): A=OH, NH2, CH3CONH, COOH, COOR or OR; R = 1-4C alkyl; B = direct bond or a linker; Hir = hirudin, desulphatohirudin or hirudin mutein gp. linked via serine, threonine or lysine chain(s); m = 100-1000; n = 2-5; p = 1-4. Pref. the linker is (a) -O-(CH2)n-1-CH= or -O-(CH2)n-1-CO-; or (b) -X-CO-, -X-CO-NH-Z-NH-CO-, -X-CH2-p-Ph-N2-, -X-CH2-CH(OH)-CH2-p-Ph-N2-, -X-CO-CH2-CH2-CO-, -X-CH2-CO- or gp. of formula (i); R1 = H, Cl or OH; X = -S-, -O-, -N(H, CH3 or C2H5)-; and Z = 2-6C alkylene or p-phenylene. USE/ADVANTAGE - (I) are anticoagulants in human and veterinary medicine to treat and prevent e.g. myocardial infarct, peripheral arterial occlusions, deep vein thrombosis and pulmonary embolism. They are administered i.v. or i.m. (I) have a half-life of 1-100 hours, compared with 50 mins. for hirudin itself and 7 hours for hirudin-dextran. Further, (I) have high activity with only very slight antigenicity.

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