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18 条记录 (耗时 0.018 秒)

    SELF-CALIBRATED ASSAY FOR DETERMINING PROTEOLYTIC ENZYME GENERATION, DEDICATED MEANS AND USES THEREOF
    2.
    发明公开
    SELF-CALIBRATED ASSAY FOR DETERMINING PROTEOLYTIC ENZYME GENERATION, DEDICATED MEANS AND USES THEREOF 审中-公开

    公开(公告)号：EP3363912A1

    公开(公告)日：2018-08-22

    申请号：EP17156656.5

    申请日：2017-02-17

    申请人： Synapse B.V.

    发明人： HEMKER, Hendrik Coenraad

    IPC分类号： C12Q1/56 ,  G01N33/86

    摘要： A method is described to measure the course of enzyme activity when a proteolytic enzyme is generated in a sample of blood or plasma.
    The activity, like in previous art, is monitored through its action on a substrate that upon action of the enzyme releases a fluorescent product.
    Contrary to previous art a small fluorescent moiety is made to be present at zero time, either because the substrate itself has native fluorescence or because a small amount of fluorescent product (0.1 - 10 mole % of the concentration of substrate) is added before the reaction starts, giving rise to a small initial signal (Fo). Also, the maximal signal ( F max ), occurring when all substrate has been converted into product is determined. The experimental fluorescent signal ( F exp .t ) is converted into the normalized ratio of the signal ( R t ) according to the formula R t =(F exp.t -F 0 )/(F max - F 0 ).
    It is demonstrated that the course of enzyme activity ( E t ) can be obtained from: E t = dR t / dt . S 0 + K m / 1 − R t / k cat .
    The use of this method has the following advantages:
    • Strong reduction of experimental noise
    • No external calibration is required, i.e. no second sample with known enzymatic activity has to be used.
    • No correction for substrate consumption is required.
    • Thrombin or plasmin generation curves obtained with macromolecular substrates can be calibrated despite the fact that such substrates are insensitive to the action of α2macroglobulin-thrombin complexes.

    Compounds and methods for inhibition of binding of ICAM-4 to platelet integrin alphaIIbbeta3
    3.
    发明公开
    Compounds and methods for inhibition of binding of ICAM-4 to platelet integrin alphaIIbbeta3 审中-公开
    用于抑制ICAM-4的结合Plättchenintegrin-AlphaIIbbeta3化合物和方法

    公开(公告)号：EP2789631A1

    公开(公告)日：2014-10-15

    申请号：EP13305468.4

    申请日：2013-04-10

    申请人： Synapse B.V.

    发明人： De Laat, Henricus Bastiaan ,  Du, Xiaoyan ,  Ruggeri, Zaverio M.

    IPC分类号： C07K16/28 ,  C07K7/08 ,  C07K11/00 ,  A61K38/10

    CPC分类号： C07K16/2848 ,  A61K38/1774 ,  A61K2039/505 ,  C07K7/08 ,  C07K14/70525 ,  C07K14/70546 ,  C07K16/2821 ,  G01N33/5044 ,  G01N2500/02

    摘要： The present invention relates to compounds and methods for inhibition of binding of ICAM-4 to platelet integrin α IIb β 3 .
    The present invention also relates to a screening method and to a kit to detect or monitor in vitro the effect of a substance, drug or pharmaceutical agent on the ICAM-4/α IIb β 3 interaction in a biological sample, while simulating blood flow conditions existing in vivo.
    It concerns in particular an anti-ICAM-4 antibody or a fragment thereof capable of blocking ICAM-4 binding to platelet integrin α IIb β 3 , or an ICAM-4 mimetic peptide blocking ICAM-4 binding to platelet integrin α IIb β 3 , or an anti-CD61 antibody or a fragment thereof capable of blocking ICAM-4 binding to platelet integrin α IIb β 3 , for use in the treatment of a thrombotic disease, and for the preparation of pharmaceutical compositions for such treatment.

    摘要翻译： 本发明涉及的化合物和方法用于抑制整联IIB±ICAM-4结合到血小板²第三 因此，本发明涉及的筛选方法和试剂盒，以检测或监测体外的物质，药物或药剂的对ICAM-4 /±IIB²3的生物样品中的相互作用的效果，同时模拟血液的流动条件 现有的体内。 它尤其涉及到抗ICAM-4抗体或能够阻断ICAM-4结合到血小板整体的片段±IIB²3，或ICAM-4模拟肽阻断ICAM-4结合到血小板整±IIB²3， 或抗CD61抗体或能够阻断ICAM-4结合到血小板整IIB±²3，用于血栓性疾病的治疗中使用的其片段，以及用于制备药物组合物用于寻求治疗的。

    DETERMINATION OF BIOLOGICALLY ACTIVE FORMS OF PROTEOLYTIC ENZYMES
    5.
    发明公开
    DETERMINATION OF BIOLOGICALLY ACTIVE FORMS OF PROTEOLYTIC ENZYMES 有权
    测定蛋白水解酶的生物活性形式的

    公开(公告)号：EP1159448A1

    公开(公告)日：2001-12-05

    申请号：EP00914107.8

    申请日：2000-03-03

    申请人： Synapse B.V.

    发明人： HEMKER, Hendrik, Coenraad ,  WAGENVOORD, Robert, Jan ,  RAMJEE, Manoj

    IPC分类号： C12Q1/56 ,  G01N33/86 ,  C12Q1/37

    CPC分类号： C12Q1/37 ,  C12Q1/56 ,  C12Q2337/12 ,  C12Q2337/22 ,  G01N33/86 ,  G01N2333/77 ,  G01N2333/811 ,  G01N2333/974

    摘要： A process is provided for the assessment of an active proteolytic enzyme in a blood or another biological fluid sample possibly comprising a complex of said proteolytic enzyme and α2-macroglobulin, wherein said sample is contacted with a substrate comprising a molecule of sufficient size coupled to a signal-substrate, said signal-substrate comprising a detectable leaving group, wherein said substrate is hydrolysed by said proteolytic enzyme but not by said complex. The proteolytic enzyme is preferably selected from the group consisting of thrombin, activated clotting factor, activated fibrinolytic factor, and activated component of the complement system. Of these, thrombin is most preferred. The molecules of sufficient size are preferably water soluble and selected from the group consisting of inert protein, preferably ovalbumin, polysaccharide, and synthetic polymer. The size of these molecules is such that they will not fit into the cavity of the α2M molecules.

    Measuring thrombin activity in whole blood
    8.
    发明公开
    Measuring thrombin activity in whole blood 审中-公开
    Volblut的Bestimmung derThrombinaktivität

    公开(公告)号：EP1717588A1

    公开(公告)日：2006-11-02

    申请号：EP05290952.0

    申请日：2005-04-29

    申请人： Synapse B.V.

    发明人： Hemker, Hendrik Coenraad ,  Al-Dieri, Raed ,  Nijhuis, Sebastiaan ,  Beguin, Suzette ,  Wagenvoord, Robert ,  Giesen, Peter

    IPC分类号： G01N33/86

    CPC分类号： C12Q1/56 ,  G01N2333/974

    摘要： The invention relates to a method for in vitro determining thrombin activity in a sample wherein the sample is a blood sample and thrombin generation is measured by the steps of:
    - contacting a layer of said sample with a fluorogenic substrate of thrombin, wherein said layer has a thickness within a range of 0.05 to 5 mm and a surface within a range of 10 to 500 mm 2 ;
    - allowing thrombin to generate in said sample;
    - measuring the fluorescence emitted from the surface of the layer, by the fluorescent group released from the fluorogenic substrate as a result of enzymatic action of generated thrombin on said fluorogenic substrate.

    摘要翻译： 本发明涉及一种用于体外测定样品中凝血酶活性的方法，其中所述样品是血液样品，并且通过以下步骤测量凝血酶产生： - 使所述样品层与凝血酶的荧光底物接触，其中所述层具有 厚度在0.05〜5mm的范围内，表面在10〜500mm 2的范围内; - 允许凝血酶在所述样品中产生; 由荧光基质释放的荧光基团，由于所产生的凝血酶在所述荧光底物上的酶促作用而测量从该表面发射的荧光。

    A METHOD AND ASSEMBLY FOR MEASURING THROMBIN GENERATION IN PLASMA
    9.
    发明公开
    A METHOD AND ASSEMBLY FOR MEASURING THROMBIN GENERATION IN PLASMA 有权
    用于等离子体测量凝血酶的产生方法和设备

    公开(公告)号：EP2313785A1

    公开(公告)日：2011-04-27

    申请号：EP09805216.0

    申请日：2009-08-05

    申请人： Synapse B.V.

    发明人： HEMKER, Hendrik, Coenraad ,  APITZ-CASTRO, Rafael, Jesus ,  NIJHUIS, Sebastiaan

    IPC分类号： G01N33/86

    CPC分类号： G01N33/86

    摘要： Disclosed is a method for measuring thrombin generation in a whole blood sample. The whole blood sample may be applied forthwith, without prior processing. The blood cells and blood plasma in the whole blood sample are separated by (lateral) flow migration. Also disclosed is an assembly of a sample support and a device dedicated to measure thrombin generation in a whole blood sample. Advantageously, the sample support comprises a separator medium allowing separation of whole blood into blood cells and blood plasma by means of (lateral) flow migration.

    Time-course measurement of enzymatic activity corrected for impacts of disturbances relating to the reaction of the enzyme with a substrate
    10.
    发明公开
    Time-course measurement of enzymatic activity corrected for impacts of disturbances relating to the reaction of the enzyme with a substrate 有权
    为了研究在该反应的底物的酶的酶活性的时间过程中的任何干扰校正的测量的影响

    公开(公告)号：EP2088435A1

    公开(公告)日：2009-08-12

    申请号：EP08151181.8

    申请日：2008-02-07

    申请人： Synapse B.V.

    发明人： Hemker, Hendrik Coenraad ,  Hemker, Pieter Wilhelm

    IPC分类号： G01N33/86 ,  C12Q1/37 ,  C12Q1/56

    CPC分类号： C12Q1/56 ,  C12Q1/37 ,  G01N2333/974

    摘要： The invention relates to time-course measurement of enzymatic activity corrected for impacts of disturbances relating to the reaction of the enzyme with a substrate.
    The in vitro method of the invention is especially intended for the measurement of clotting or the fibrinolysis activity in vitro .
    The invention enables to measure the exact time course of an enzymatic activity that develops and/or disappears in a reaction mixture, especially in a blood sample.
    The invention thus relates to a method of determination of the course of an enzyme activity that is variable in time, wherein said activity is probed by conversion of a substrate of the enzyme, comprising, in a selected test set up and for a determined substrate of the enzyme, the determination of the velocity of signal production (dF diag /dt) resulting from a time curve of the signal (F diao =f(A)) obtained from splitting said substrate when it is contacted with a determined initially fixed concentration of the enzyme (E) and providing a "diagnostic plot" with the values of (dF diag /dt) against the signal (F diag ) and determining whether said diagnostic plot is either a straight line or a parabola and in the same test conditions, for a given test sample, the determination of the signal production (F exp ) resulting from splitting the substrate by the enzyme generating in and/or disappearing from the sample and providing the time curve of signal F exp =f(t); and transforming the obtained experimental value of the signal (F exp ) into an ideal value (F transf )

    摘要翻译： 本发明涉及一种用于干扰涉及所述酶的与底物反应的影响校正酶活性的时间过程的测量。 本发明的体外方法的目的是尤其是对凝血的测量或体外纤维蛋白溶解活性的爱。 本发明能够测量的酶活性的确切时间进程没有开发出和/或消失在反应混合物中，爱尤其是血液样品。 因此，本发明涉及确定的酶活性的过程的方法所做的是在时间上可变的，worin所述活性是通过设置了酶，其包括，在所选择的测试的底物的转化率和对的确定性开采衬底探测 酶，信号生成（DF DIAG / dt）的速度的确定从分束而获得的信号（F刁= F（A））的一个时间曲线得到的所述基板当它与的确定性开采INITIALLY固定浓度接触 酶（e）和提供“诊断图”与针对信号（F DIAG）的值（DF DIAG / DT）和确定性采矿是否所述诊断图可以是一个直线或抛物线，并在相同的试验条件， 对于给定的测试样品中，信号生成（F EXP）从由酶产生中和/或从样品中消失，并提供信号F EXP = F（t）的时间曲线分割衬底得到的测定; 和将所述信号（F EXP）的所获得的实验值成理想值（F TRANSF）