CN1036155C - 诊断和识别胸痛早期发作的诊断盒 - Google Patents
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Abstract
本发明公布的诊断用诊验盒是为了评价在患者胸痛发作初期究竟胸痛是否源于心脏,以及将变异性心绞痛和心脏梗塞区别开。该试验盒是由一个为接受和保留患者血液和血清样品的接受器和悬浮于载体上的至少三个单克隆和多克隆抗体。每个抗体与一不同的蛋白相互补,该蛋白是在心肌梗塞早期从心肌中释放的,每个抗体有相应的试剂,后者对每个抗体与相应蛋白反应时作出独立的应答。对试剂作出应答的综合提示了患者诊断时的状况。
Description
本发明涉及新的药板形式的一步诊断试验法,用来作为一种精确、简便、迅速和便携的诊断方法,以判断患者的胸痛是否源于心脏,并在患者胸痛的早期发作时区别出是易变性心绞痛还是心肌梗塞(“MI”)。特别是本药板用酶免疫试验夹层干化学形式同时测定了心脏受损伤时或损伤后血清或血浆中出现的三种不同的物质或标示物的水平。在本发明的优选的实施例中,这三个标示物是肌酸激酶(CK),肌红蛋白和肌浆球蛋白轻链(MLC)。
心肌梗塞的紧急诊断取决于内科长征的敏锐性和对患者症状的评估,例如胸痛或胸压迫感,显可能放射到下到臂部,上到颈部,疲劳,要死的感觉,呼吸短促,苍白,皮肤冷湿,外周发绀或数丝状脉。
大多数北美的胸痛患者在发作6小时内报告给医生或急诊室。因此,在MI早期阶段进行有效的诊断试验是至关重要的。
有数种心脏检查方法用于诊察MI。这些检查方法包括ECG,SGOT/AST,LDH,CK-MB免疫试验和NA乳液肌红蛋白颗粒增强试验。然而还没有用单一酶心脏检查法能使急诊室医生确定胸痛是来自心脏或不是来自心脏的原因。而且只有在确证了是心肌梗塞后,才开始溶解血栓的治疗。这种治疗开始得越早,患者完全康复的可能性就越大或至少使心脏损伤只在最低程度。因此,内科先生确定这种疼痛是心脏性的还是非心脏性的,是至关重要的。
心电图(ECG)可用来诊察MI。然而只有心脏受到严重损伤时心电图才能诊断出。ECG的诊断特异性对开始阶段的胸痛只有51%。因此,ECG不适宜用于MI的早期诊察。
血清谷氨酸草酰乙酸转氨酶/天门冬氨酸转氨酶(SGOT/AST)在心肌中有高浓度,是占优势的酶。血清试验测定SGOT水平可用来诊断心肌梗塞。然而,SGOT只在胸痛发作后的大约8-10小时后才开始升高,在24-36小时内达到峰值,5-7天后恢复正常。患者在胸痛早期和紧急处置时SGOT在诊断心肌梗塞上是没有特殊帮助的。SGOT对心肌也不是特异的。已发现许多包含骨骼肌的组织,如肝和肾脏,由于肌肉注射,休克,肝脏病和肝充血时,SGOT被释放,因此这在诊察特异的心脏组织损害上价值不大。
乳酸脱氢酶(LDH)在许多组织中浓度很高,这些组织包括心脏,骨骼肌和肝脏,检查血清中LDH的存在的试验被用来诊断心肌梗塞。在五种普通的同型中心脏主要含有LDH1和LDH2。胸痛发作24-36小时后LDH水平开始增高,48-72小时后达峰值,4-8天后回复正常。因此,患者在胸痛早期不能用LDH作为MI的指标。此外对心脏损伤LDH不是特异的,在肺栓塞、溶血,肝充血,肾脏病和骨骼肌损伤时LDH会出现。这种特异性的缺乏降低了LDH作为诊断手段的应用。
肌酸激酶(CK)是肌肉组织中的一种酶。CK催化肌酸和三磷酸腺苷(ATP)转变为磷酸肌酸和二磷酸腺苷(ADP)的反应。CK的数个同功酶中的CK-MB在心脏组织中。CK-MB对诊查心肌梗塞是个灵敏的标示物,因为它在心肌组织受损伤时释放出。故而CK-MB存在于受损伤患者的血清之中,图1说明了患者血清中CK浓度与时间的关系(文献Lee T.H.等(1986)Ann.Intern.Med.105,221-233)。
CK-MB免疫试验是诊断心肌梗塞的标准检查法。美国专利No 4900662公布了CK-MB的应用方法,题目是“CK-MM心肌梗塞免疫试验”。
Shah在USP 4900662中公布了在患者心肌梗塞后测定血清中初始增高的CK-MM-a(CK-MM的异型)浓度和同时测定CK-MM-a和CK-MM-b的方法。用这个方法可提供一种对梗塞的时间的精确估计。该方法包括测定血清中CK-MM-a和CK-MM-b的总浓度和CK-MM-a的浓度,以确定心肌梗塞急性期的时间。公布的试剂包括有CK-MM-a的多克隆抗体和单克隆抗体,这类抗体并不明显地与CK-MB,CK-MM-b或CK-MM-c结合,有抗CK-MM-b抗体,它不会明显地与CK-MB,CK-MM-a或CK-MM-c结合,有抗CK-MM-a+b抗体,它可与CK-MM-a和CK-MM-b结合,但不能明显地与CK-MB或CK-MM-c结合,还包括这些抗体的标记的衍生物,固着这些抗体的不溶性的支持物,以及含有一种或多种这些试剂的药盒。酶标记的和放射性标记的CK试剂特别有用。
单独使用CK-MB作为诊断标示物是有些困难的。首先,心肌梗塞发作后只有在6-8小时后CK-MB的血清浓度才增高,而且12小时后才达峰,造成早期紧急诊断和治疗的困难。
第二,CK-MB试验必须在实验室中由训练有素的技术质进行。在非城区不易进行这样的试验,结果也不能迅速得的解析,致使延误了诊断,因此,就患者等侯诊断的住院费而言,增加了保证机构的负担。
第三,CK-MB处于正常骨骼肌组织中,因此,使该试验结果对心脏不够特异,诊断不够肯定。
肌红蛋白是位于骨骼肌或心肌细胞膜的邻近的另一种蛋白质。细胞膜的通透性一旦变得异常,例如心脏缺血时的一个可逆状态,肌红蛋白立即被细胞排出。在胸痛发作1.5小时内,在血清中即可检查出肌红蛋白。医学研究团体认为,心肌坏死释放肌红蛋白,因此它是心肌损伤的一个有用的早期标示物。图2说明了血清中肌红蛋白浓度与时间的关系(文献:Grenadier E.等(1981)Am.Heart J.105,408-416;Seguin J.等(1988)J.Thorac Car-diovasc Surg.95,294-297)。
胸痛发作后2-3小时内若未检查出血清肌红蛋白水平增高,则在确定疼痛原因时可排除急性心肌梗塞。
“NA乳液肌红蛋白颗粒增强测定”是检查肌红蛋白的市场有售的药盒。这种检查试验是基于人体体液中存在的抗原与共价链偶联于聚苯乙烯颗粒上的抗肌红蛋白抗体间的反应。把样品、N肌红蛋白试剂、一种除掉非特异性反应的溶液和N反应缓冲液自动地移液到比包池内,温孵12分钟后用浊度法测定光散射,同标准曲线计算肌红蛋白的浓度。
放射免疫试验也可测定肌红蛋白,但还有一种无酶联结的免疫吸附剂检验(ELISA)装置也能采用。
单用肌红蛋白指标诊断心肌梗塞具有困难性。肌红蛋白不能指出心肌操作的特殊类型,例如心肌梗塞,在像休克、肾脏病,横纹肌溶解和肌病等各样不同的情况下,也可有肌红蛋白存在。此外,血清和血浆中肌红蛋白的浓度通常随年令与性别而变,健康的正常人浓度变化范围很宽,血清浓度高达90ug/l时通常认为是健康人群的高限。因此,对此人可能是正常水平的浓度,对其它人就可能是严重问题的指征,做诊断时要比预料的准确度略差。
肌浆球蛋白轻链(MLC)是肌浆球蛋白肌原纤维的整体部分,但其功能尚不清楚,MLC存在于快、慢、心房和心室肌肉之中,已知MLC对心脏缺血非常敏感。心肌坏死后血清中迅速出现MLC,提高的浓度可维持长达10天,图3说明了患者血清中MLC浓度与时间的关系(文献:Wang J.等(1989)Clin.Chimica Acta 181,325-336;Jackowski G.,Symmes J.等(1989)Circulation Suppl 11,80,355)。
MLC确定溶血栓治疗是否成功也有预后的价值。MLC的浓度越高,预后越差,也表明梗塞越严重。在数天内浓度下降表示患者趋于康复,而高高低低或平台样曲线表明有梗塞趋势需做手术。
MLC主要有两种,称作MLC1和MLC2,存在于心肌细胞胞浆的可溶性库中,也可完整的存在于肌浆球蛋白肌原纤维中,心室肌细胞中的MLC2,或许还有MLC1与慢骨骼肌细胞中的同型是一样的。心脏疼痛患者的MLC1水平提高80-85%。MLC1对易变性心绞痛和冠心病是非常灵敏的指征。
其它类的心脏标示物,如低分子量的心肌蛋白(LMWCP)可作为心脏的标示物。这类标示物的实例包括收缩器官的成分,即肌钙蛋白,肌钙蛋白-T,肌钙蛋白-I和肌钙蛋白C,线粒体酶,如三糖P异构酶,易自心脏释放出的低分子量多肽,以及局部缺血发作后早期就释放的肌纤维膜蛋白或蛋白片数,特别是分子量为15kd的肌纤维膜蛋白和100kd的复合糖蛋白对心脏是特异的。
该心脏肌钙蛋白-I同型可抑制心肌收缩间静止期的肌纤蛋白和肌浆球蛋白分子间的相互作用。在MI后4-6小时内患者血清内出现肌钙蛋白I,并且这种增高的水平持续7-8天。图4说明了肌钙蛋白-I浓度与时间的关系。(文献:CumminsB.,Auckland M.L.和Cummins P.(1987)Am.Heart J.113,1333-1344)。肌钙蛋白-I对心脏是特异的标示物,在诊查是心肌损伤还是骨骼肌损伤时,比其它标示物更灵敏。
肌钙蛋白-T是薄丝状的肌钙蛋白-原肌球蛋白的复合物的构成成份,联结原肌球蛋白骨架和肌钙蛋白-I肌钙蛋白C复合物,肌钙蛋白-T是个碱性蛋白质,在心脏和快、慢骨骼肌中具有同型。MI发作后3小时内血清中即出现并且增高的水平至少持续10天。图5说明了肌钙蛋白-T的浓度与时间的关系(文献:Katus H.A.等(1989)J.Mol.CellCardiol.21,1349-1453)。肌钙蛋白-T的释放按双相的样式,对心脏是特异的,并且对MI非常灵敏。
肌浆球蛋白重链(MHC)和原肌球蛋白是分子量较大的蛋白质,也可作为心脏的标示物。MHC是肌肉主要收缩蛋白的构成部分。在心肌细胞坏死和随后的膜的不可逆损伤后,MHC的片断就会由心室中释放到血清中。虽然在心肌细胞坏死后,MHC片断不会迅速出现于血清中,但在MI后MHC增高的浓度至少持续10天,并且在MI后第4天可观测到MHC的峰值。图6说明了MHC浓度与时间的关系(文献:Leger J.O.C.等(1985)Eur.J.of Clin.Invet.15,422-429;Sequin J.R.等(1989)J.Thorac.Cardiovase Surga,98,397-401)。MHC释放曲线下面积与心肌细胞损伤程度有非常好的相关性。然而在MI的急性期MHC水平对临床价值不大。
原肌球蛋白是由两个多肽形成的二聚体,是肌肉收缩的调节系统的构成部分。在心肌梗塞发作后大约7-8小时,可检测出血清中的原肌球蛋白。如同CK-MB-样,它对心肌梗塞非常敏感。图7说明了原肌球蛋白浓度与时间的关系(文献:CumminsP.等(1981)Clin.Sci.60,251-259)然而,骨骼肌损伤时,原肌球蛋白的浓度也会增高,因此它不是心脏特异性的。
现用的心肌梗塞的标准诊断方法都有局限性。在胸痛发作后,没有一种方法能立即提供非常灵敏、特异迅速和简便的诊断检查,例如在急救车或医生办公室中。
本发明是在胸痛发作的早期测定患者血液或血清中因心脏损伤存在的至少三种不同的标示物,并将它们综合在一起,以提供一种心肌梗塞诊断的改良方法,用于易变性心绞痛或MI的早期诊断。
以前的诊断方法的缺陷可用一种准确、快速和便携的一步式诊断板加以克服,以用于急诊处置中检测心脏受损伤的患者血清中存在的至少三种标示物。试验结果将确定患者是患了易变性心绞痛还是心肌梗塞。MI的早期诊断仍能在早期开始进行溶血栓治疗。因而心脏损伤会降到最低水平,从而增加了患者的生存机会。即使在疼痛发作数天之后,本诊断板的试验结果也可以区分易变性心绞痛和心肌梗塞。该诊断板是利用酶免疫试验夹层干化学型板。用这种板进行系列的短暂的测定,可为内科医生提供关于心脏损伤的程度和溶血栓处置的预后的信息。本发明的优越实施例中,这三个标示物是肌酸激酶(CK),肌红蛋白和肌原纤维轻链(MLC)。
本发明的一个内容是提供了一种诊断用试验盒,用以在患者胸痛的早期发作时检查出心肌梗塞。该试验盒包括一个可容纳和保留患者血液或血清样品的贮存部和一个与血样进行反应的检测装置。该检测装置的组成是,至少有三种悬浮于载体上的单克隆或多克隆抗体,每一种抗体与早期心肌梗塞时自心肌释放的不同的蛋白质相互补,以及独立地与应答 互补的蛋白进行反应的各个抗体的相应的试剂。与试剂反应的效果的综合,应提示诊断时患者心脏的状况。
本发明的实施例用图加以说明。
图1是血清中CK浓度与时间的关系作图;
图2是血清中肌红蛋白浓度与时间的作图;
图3是血清中MLC浓度与时间的作图;
图4是血清中肌钙蛋白-I浓度与时间的作图;
图5是血清中肌钙蛋白-T浓度与时间的作图;
图6是血清中MHC浓度与时间的作图;
图7是血清中原肌球蛋白浓度与时间的作图;
图8是优选的实施例的平面观;
图9是图8实例的分解透视图;
图10是图18的实例中膜的偏斜图;
图11是膜的第二个实例的偏斜图。
本发总的用图8加以说明。本发明的优选实例是一块如1所示的板。
所用板的样式是已知的,可以买到,该板的形状与现用的综合妊娠试验板相似,可以买到,商品名为BIOSIGN。
板是由聚丙烯片构成,分前板10和后板12。前板10有一显示窗口14,每一个心脏标示物对应一个口,还有一个样品口16,如图9所示。在前板10下面有一块暴露的干化学膜18,后者用适当的方法粘连在前板10的背面。后板12有个绕其一周的边20,以与前板10严格扣合。这样,把膜18封在前后板之间。
前板和后板的扣合如所述的那样,但还有许多其它的适宜的联结方法,对熟悉此类技艺的人来说这是明显的。
前板10也能提供一块区域13,上面可写上患者的姓名和身份,也可用来书写测定结果。
关于图10,膜18是单克隆和多克隆抗体的载体。在优选的实例中,将血液或血清按箭头方向由一端流向另一端。端点22与样品窗口16对在一起。固定不动的抗体26层压在或连到抗体结合物24上,后者针对抗原的不同的表位,而不会被抗体26识别。抗体24与肌浆球蛋白互补。同样,抗体30层压在相应的试剂28上。抗体30互补于CK-MB。同样,抗体34层压在试剂32上。抗体34与肌浆球蛋白轻链互补。抗体38与正常血液或血清中存在的任何蛋白互补。抗体38层压在试剂36上。
单克隆和多克隆抗体可用常规方法,由制备多克隆抗体的哺乳动物中制取。
在优选实例中用标记的试剂,该抗体试剂标记到或用化学方法键合于可被观测或测定的特定的部位,以便对血清或血液中存在的或干化学膜上分析物的存在加以验证或定量。可以与本发明的用作诊断工具的抗体相结合的配基和基团,包括有元素、化合物或生物物质,它们所具有的物理或化学特性可用来区别与它们链合的抗体与其它的抗体。
每个心脏标示物至少需要两种类型为单/多或兔/多,山羊/多的抗体。这些抗体对它们的心脏免疫原进行亲合性纯化,再用交叉吸附法对非相关种属的免疫原进一步纯化,以除去非特异性免疫球蛋白。
使用时诊断师例如内科医生、急救车护理或护士将三滴或低于100ul的患者血清或血液加到样品窗口16中。样品会由于毛细作用沿膜18移动并相继与抗体和试剂对(24和26,28和30,32和34以及36和38)相接触。
若血样中有特异的心脏标示物,则与固定在膜上的抗体相结合。相应的试剂也会与之反应并可由抗体被固定在膜上时颜色的改变而看出,这种颜色的变化与血样中标示物的浓度成比例。这样,若在一定时间间隔用此试验盒检查,可以确定标示物的浓度增高或降低,作为诊断工具。在3-5分钟内就能完成检查结果。
在优选的实例中,测定的样品中的各个心脏标示物均会出现一个蓝色色带。色带的深浅强度可用反射计定量,颜色的强度与特定的标示物的浓度相关。反射计可包括有微处理机,在板上被检测的每个心脏标示物的定量结果以浓度大小和患者的姓名或身份一起打印出来。
用三滴或低于100ul的血清或血浆测定时,标示物的浓度为0.5ng/ml-25ng/ml最为敏感,每次测定和数次测定之间的精确度,变异系数低于15%。
在测定中所用的心脏标示物将取决于那些标示物的性质。优选实例用的板有肌红蛋白、MLC和CK-MB,如图8所示。
肌红蛋白从心肌细胞中释放非常早,它不是心脏所特异的,对心肌梗塞和坏死有非常高的灵敏性,在无坏死情况下的缺氧损伤是不会释放出的。MLC是心脏特异性的,用以区别心脏性的和非心脏性的疼痛,它的释放也快但不像肌红蛋白那样快。CK-MB可将心绞痛和心肌梗塞区分开,但只有在胸痛发作6小时后才能检测出,因此不能单独用于急诊诊断。
如果所用的心脏的三个标示物是CK-MB,肌红蛋白和MLC,参考图1,2,和3,其结果对诊断可用如下的解析。
若诊断板显示阳性的MLC和阴性的肌红蛋白和CK-MB,则提示患者的胸痛是心脏性的,原因是易变性心绞痛。
若肌红蛋白和MLC是阳性结果,CK-MB是阴性的,提示为早期心肌梗塞,可开始干预治疗。
若三种都是阳性结果,提示为心肌梗塞。
若MLC和CK-MB是阳性,肌红蛋白为阴性,则提示为心肌梗塞。
若肌红蛋白和CK-MB为阳性而MLC为阴性,则患者可能有骨骼肌损伤(假阳性)或是心肌梗塞中期。
在这种情况下该试验不能区分假阳性和“小”的心肌梗塞,因为MLC释放曲线在数个间隔中稍许下沉,病人可能有轻度心内膜下梗塞,并且在“下沉”时刻测定。当梗塞很小时,这种“下沉”几乎达到正常水平,因而测定的患者MLC为阴性。阳性诊断要依赖于CK-MB的存在。
心肌梗塞大的患者,MLC的“下沉”并不大到与正常水平一样,因此MLC仍可检测出。
其它实例的试验板是用同样的格式,抗体有不同的组合,这样来评估心脏的不同的标出物。
为了保证在患者胸痛的早期能用这种试验板检测出心肌组织的损伤,必须用至少一种相应于在心脏损伤的初期有大量的存在的标示物的抗体,即例如CK,肌浆球蛋白轻链或肌球蛋白。具有CK、肌浆球蛋白轻链或肌球蛋白特征和性质的低分子量心脏蛋白也可用在药盒中,
适宜的蛋白和酶可选自:肌钙蛋白,肌钙蛋白-I,肌钙蛋白C,肌钙蛋白-T和肌纤维膜蛋白,三糖磷酸异构酶或者具有肌酸激酶、肌浆蛋白轻链或肌球蛋白特征和性质的各种重分子量心脏蛋白。
其它蛋白质例如原肌球蛋白和肌浆球蛋白重链也可加到诊断盒中。如果患者前来求诊是在胸痛发作许多小时后而且患者的MI处于较晚阶段,则该试验盒可检测MI。
第二个实例是膜18上可有一层被捕获的抗体126及相应的试剂124。同样为了检测其它各个标示物,要有成对的相应的抗体和试剂,即128和130,132和134以及对照组对136和138。使用时,把血样滴到每对试药上,用上述相同的方式读出结果。
干化学膜118可用吸收性物质120支持。吸收性物质120可增加血清向膜内的透入力。
另一个试验盒的实例是用血样品管,这种管通常用来从患者身上抽取血样,管的内壁作为单克隆和多克隆抗体及试剂的载体。从患者身上抽取血样后,使用者只要振摇样品管,抗体就会与血液反应。如果血液中存在心脏蛋白,就会发生如前所述的颜色变化。
本发明书虽然对优选实例作了阐述和说明,但不要认为本发明只局限于这些持定的实例。对本技术熟悉的会作许多变换和改进。本发明的界定可参见权利要求。
Claims (18)
1.一种对患者进行易变性心绞痛和心肌梗塞鉴别诊断的诊断盒,它包括:
(I)一个可接受和保留患者血液或血清样品的贮存部;和
(ii)一个与贮存部相连的检测装置,它包括:
a)彼此以一定的距离单独固定在一固定载体上的三种或多种单克隆或多克隆抗体,每一抗体与一种在心脏损伤过程中由心肌释放出的不同标示物蛋白互补,并且每一抗体可与样品接触,其中至少一种抗体与心绞痛特异性标示物蛋白互补,且至少另一种抗体与MI特异性标示物蛋白互补,和
b)独自对所形成的每种抗体/蛋白结合物作出反应并且共同为患者是否患有易变性心绞痛或MI作出反应的必要试剂。
2.根据权利要求1的诊断盒,其中所述试剂在每一抗体与其互补蛋白反应时所提供的应答是可见的颜色变化.
3.根据权利要求1或2的诊断盒,其中所说的贮存部和检测装置形成一个整体结构,其中含有干化学品形式的所说抗体和所说试剂。
4.根据权利要求3的诊断盒,它呈卡片状,包括一个前板、一个后板和一个用于将前后板及夹在其中的检测装置固定在一起以形成所说的整体单位的密封装置,其中前板包括一个用于接受样品的样品窗和一个用于显示试剂的显示窗。
5.根据权利要求4的诊断盒,其中抗体的载体是干化学膜。
6.根据权利要求5的诊断盒,其中所说的膜是被吸收性物质支持,以增强样品向检测装置渗入。
7.根据权利要求6的诊断盒,其中所说的膜通过样品窗一直延伸到显示窗,且抗体与相应的试剂在从样品窗到显示窗呈间隔关系。
8.根据权利要求4至7任一项的诊断盒,其中所说的前板被标记以鉴定蛋白质抗体反应的定位。
9.根据权利要求8的诊断盒,其中所说的前板还连接一反射计,以定量分析样品中蛋白的浓度。
10.根据权利要求3的诊断盒,其中所说的贮存部是一个可密封的清洁容器,且所说的检测装置位于该容器的侧壁。
11.根据权利要求1的诊断盒,其中所说的检测装置包括a)三种或多种固定在固体载体上不同位置的第一抗体,且每一抗体与一种在心肌梗塞过程中从心肌释放出的不同标示物蛋白互补,和b)相应的三种或多种第二抗体,每一第二抗体携带了一可检测标记且每一抗体与所述标示物蛋白上的不同抗原决定基互补从而能够与结合的标示物蛋白结合,并通过其相应的标记证明结合蛋白的存在。
12.根据权利要求11的诊断盒,其中所说的被标记的第二抗体是抗体一酶结合物,携带了活性酶作为可检测标记,且检测装置包括合适的酶底物以及用于检测酶在其底物存在下的活性的装置。
13.根据权利要求12的诊断盒,其中所说的抗体与下列蛋白质或酶的至少三种互补:肌酸激酶、肌红蛋白、肌浆蛋白轻链、肌浆蛋白重链、原肌球蛋白,肌钙蛋白、肌钙蛋白-I、肌钙蛋白-C、肌钙蛋白-T、肌纤维膜蛋白、三糖P异构酶或具有肌酸激酶、肌红蛋白或肌浆蛋白轻链的特征和性质的低分子量心脏蛋白,其中一种抗体与肌红蛋白互补,另一种抗体与肌浆球蛋白轻链互补。
14.根据权利要求13的诊断盒,其中三种抗体分别与肌酸激酶、肌红蛋白和肌浆球蛋白轻链互补。
15.根据权利要求14的诊断盒,其中所说的检测装置也包括与在正常情况下在血清中所发现的蛋白互补的对照抗体以及对对照抗体与互补蛋白反应作出应答的相应试剂,从而该应答能够证明检测是否有效。
16.根据权利要求15的诊断盒,其中所说的对照抗体与相应蛋白位于载体上距离样品窗最远处,以证明试验完全完成。
17.根据权利要求16的诊断盒,它在用少于100μl样品时对0.5ng/ml-25ng/ml的标示物浓度是灵敏的,每次测定和数次测定的准确度变异系数低于15%。
18.一种用于对患者进行易变性心绞痛和心肌梗塞的鉴别诊断的诊断盒,该盒包括:
一前板,它包括一样品窗和显示窗,样品窗接受该患者的血清或血浆样品,
一后板,
一位于前板和后板之间的干化学膜附加物,其位置至少在显示窗显示,
其中,所说膜包括:
一样品区和对照区,该样品区用于接受来自样品窗的样品;和
至少三个抗体对,它们以分离方式沿该膜分布在样品区和对照区之间,每一该抗体对包括一抗体试剂成分和一固定的捕获抗体成分,第一捕获抗体成分被固定在该膜上比相应抗体试剂成分更靠近对照区的地方,每一抗体对真有被每一抗体对的抗体试剂成分标记或化学结合的可测或可观察的部分,
该抗体对为单克隆或多克隆的,包括:
特异性结合肌红蛋白的第一抗体对,
特异性结合肌浆球蛋白轻链的第二抗体对,和
特异性结合选自CK-MB、肌钙蛋白-I和肌钙蛋白T的至少一种蛋白质的第三抗体对,
因此,在样品被加到样品窗后,存在于样品中且与抗体对互补的分析物将向对照区移动,与互补于分析物的抗体对结合,产生与分析物浓度成比例的颜色变化。
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DE (1) | DE4122886C2 (zh) |
ES (1) | ES2070658B1 (zh) |
FR (1) | FR2667944B1 (zh) |
GB (1) | GB2248688B (zh) |
IT (1) | IT1251682B (zh) |
MX (1) | MX9101550A (zh) |
NZ (1) | NZ239938A (zh) |
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-
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- 1990-10-12 CA CA002027434A patent/CA2027434C/en not_active Expired - Lifetime
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1991
- 1991-05-03 US US07/695,381 patent/US5290678A/en not_active Expired - Lifetime
- 1991-06-04 GB GB9111965A patent/GB2248688B/en not_active Expired - Lifetime
- 1991-07-11 DE DE4122886A patent/DE4122886C2/de not_active Expired - Lifetime
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- 1991-09-25 NZ NZ239938A patent/NZ239938A/en not_active IP Right Cessation
- 1991-09-30 ES ES09102146A patent/ES2070658B1/es not_active Expired - Fee Related
- 1991-10-03 AR AR91320837A patent/AR247634A1/es active
- 1991-10-09 JP JP3262301A patent/JP2628421B2/ja not_active Expired - Lifetime
- 1991-10-10 IT ITMI912687A patent/IT1251682B/it active IP Right Grant
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- 1991-10-11 FR FR9112584A patent/FR2667944B1/fr not_active Expired - Lifetime
- 1991-10-11 CN CN91109633A patent/CN1036155C/zh not_active Expired - Fee Related
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Also Published As
Publication number | Publication date |
---|---|
AU654672B2 (en) | 1994-11-17 |
JPH04258765A (ja) | 1992-09-14 |
US5290678A (en) | 1994-03-01 |
KR0167564B1 (ko) | 1999-03-30 |
ES2070658B1 (es) | 1995-12-16 |
CA2027434A1 (en) | 1992-04-13 |
CN1060533A (zh) | 1992-04-22 |
AR247634A1 (es) | 1995-01-31 |
GB2248688B (en) | 1995-07-12 |
DE4122886C2 (de) | 2000-03-02 |
AU8475791A (en) | 1992-04-16 |
ITMI912687A1 (it) | 1993-04-10 |
IT1251682B (it) | 1995-05-19 |
DE4122886A1 (de) | 1992-04-16 |
BR9104431A (pt) | 1992-06-09 |
BE1004994A5 (fr) | 1993-03-16 |
ITMI912687A0 (it) | 1991-10-10 |
KR920008491A (ko) | 1992-05-28 |
CA2027434C (en) | 1999-01-05 |
JP2628421B2 (ja) | 1997-07-09 |
NZ239938A (en) | 1994-03-25 |
GB9111965D0 (en) | 1991-07-24 |
FR2667944A1 (fr) | 1992-04-17 |
MX9101550A (es) | 1992-07-08 |
ES2070658A1 (es) | 1995-06-01 |
FR2667944B1 (fr) | 1993-07-30 |
GB2248688A (en) | 1992-04-15 |
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