CN115517243B - 一种血浆保存液、凝血质控品及其应用 - Google Patents
一种血浆保存液、凝血质控品及其应用 Download PDFInfo
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- CN115517243B CN115517243B CN202211211394.6A CN202211211394A CN115517243B CN 115517243 B CN115517243 B CN 115517243B CN 202211211394 A CN202211211394 A CN 202211211394A CN 115517243 B CN115517243 B CN 115517243B
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- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims abstract description 24
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- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 claims abstract description 12
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Classifications
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0205—Chemical aspects
- A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
- A01N1/0226—Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
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- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Environmental Sciences (AREA)
- Dentistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- Physiology (AREA)
- Medicinal Chemistry (AREA)
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- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
本发明涉及生物技术领域,尤其涉及一种血浆保存液、凝血质控品及其应用。该血浆保存液由烟酰胺、三羟甲基氨基甲烷、蔗糖、抑肽酶、氯化镁、氯化锰、防腐剂、消泡剂和pH调节剂组成,采用该血浆保存液制备的液凝血质控品不存在基质效应,稳定性高,PT、APTT、TT、FIB、AT‑III五项凝血检验的值在正常人凝血指标内,满足PT、APTT、TT、FIB、AT‑III五项凝血检验的质量控制需求。
Description
技术领域
本发明涉及生物技术领域,尤其涉及一种血浆保存液、凝血质控品及其应用。
背景技术
人体内抗凝系统及纤溶系统共同构成机体内两个重要的防御系统,与凝血系统形成既对立又统一的功能系统,保持动态平衡,使机体可在出血时有效地止血,又可防止血块堵塞血流,从而使血液保持液态。目前,凝血系统检测应用最广泛的是凝血系统筛选试验中的PT、APTT、TT。抗凝系统中的抗凝物质使得血液不会发生凝固,抗凝系统包括细胞抗凝系统和体液抗凝系统,体液抗凝系统中的主要抗凝物质为抗血酶(AT III)。纤维蛋白溶解系统的主要功能是使纤维蛋白凝块溶解,保证血流通畅,另外也参与组织的修复和血管的再生。
目前,国内应用的凝血质控品多为国外进口产品,通常只包括PT,APTT项目,相对较少厂家包含五个检测项目,且稳定性较短,价格昂贵,产品不易获得。
发明内容
有鉴于此,本发明提供了一种凝血质控品及其应用。该凝血质控品不存在基质效应,稳定性高,PT、APTT、TT、FIB、AT-III五项凝血检验的值在正常人凝血指标内,满足PT、APTT、TT、FIB、AT-III五项凝血检验的质量控制需求。
为了实现上述发明目的,本发明提供以下技术方案:
一种血浆保存液,包括:烟酰胺、三羟甲基氨基甲烷、蔗糖、抑肽酶、氯化镁、氯化锰、防腐剂、消泡剂、pH调节剂和水。
一些实施方案中,血浆保存液中各组分含量为:
烟酰胺122.14~244.24g/L、三羟甲基氨基甲烷100~300mM/L、蔗糖100~300g/L、抑肽酶10000~100000KIU/L、氯化镁0.5~5mM、氯化锰0.5~5mM、防腐剂2.5~5.0g/L、消泡剂5~15g/L,采用pH调节剂调节pH至7.0~7.9。
一些实施方案中,血浆保存液中各组分含量为:
烟酰胺244.24g/L、三羟甲基氨基甲烷200mM/L、蔗糖200g/L、抑肽酶80000KIU/L、氯化镁1~4mM、氯化锰1~4mM、防腐剂4g/L、消泡剂10g/L,采用pH调节剂调节pH至7.0~7.9。
一些具体实施例中,血浆保存液中各组分含量为:
烟酰胺244.24g/L、三羟甲基氨基甲烷200mM/L、蔗糖200g/L、抑肽酶80000KIU/L、氯化镁2mM、氯化锰3mM、防腐剂4g/L、消泡剂10g/L,采用pH调节剂调节pH至7.8。
本发明提供的血浆保存液中:所述消泡剂为B-400水性消泡剂、T-2318中的至少一种;所述防腐剂为所述防腐剂为叠氮钠、吡硫钠、庆大霉素中的至少一种;所述pH调节剂为盐酸、甘氨酸中的至少一种。
本发明还提供一种凝血质控品,由所述的血浆保存液和血浆组成。
所述凝血质控品的PT、APTT、TT、FIB、AT-III值均在正常人凝血指标内。
一些实施方案中,所述血浆保存液和血浆的体积比为(0.05~0.15):(0.85~0.95)。
一些实施方案中,所述血浆制备方法如下:将血液与抗凝剂混合,2000~2500离心30min,收集上清液,获得血浆。
一些实施方案中,所述血液和抗凝剂的体积比为1:9;所述抗凝剂为2~5wt%柠檬酸三钠水溶液。
本发明还提供了所述凝血质控品的制备方法,包括:
将烟酰胺、三羟甲基氨基甲烷、蔗糖、抑肽酶、氯化镁、氯化锰、防腐剂、消泡剂混合,加入pH调节剂调节pH至7.0~7.9,然后加入血浆,获得凝血质控品。
本发明还提供了所述凝血质控品在制备凝血检测试剂中的应用。
其中,所述凝血检测的指标包括PT、APTT、TT、FIB、AT-III中至少一种。
本发明提供一种血浆保存液、凝血质控品及其应用。所述血浆保存液由烟酰胺、三羟甲基氨基甲烷、蔗糖、抑肽酶、氯化镁、氯化锰、防腐剂、消泡剂和pH调节剂组成,采用该血浆保存液制备的凝血质控品不存在基质效应,稳定性高,PT、APTT、TT、FIB、AT-III五项凝血检验的值在正常人凝血指标内,满足PT、APTT、TT、FIB、AT-III五项凝血检验的质量控制需求。
具体实施方式
本发明提供了一种血浆保存液、凝血质控品及其应用。本领域技术人员可以借鉴本文内容,适当改进工艺参数实现。特别需要指出的是,所有类似的替换和改动对本领域技术人员来说是显而易见的,它们都被视为包括在本发明。本发明的方法及应用已经通过较佳实施例进行了描述,相关人员明显能在不脱离本发明内容、精神和范围内对本文的方法和应用进行改动或适当变更与组合,来实现和应用本发明技术。
凝血:哺乳动物血液凝固是一个复杂的生理生化代谢过程,其实质是通过一系列酶促反应,使血浆中呈液态的纤维蛋白原转变成固态的交联纤维蛋白,简称凝血。各链锁反应的多种物质称凝血因子,它们的化学本质,除钙离子外,绝大多数为蛋白质。凝血过程可分为凝血酶原激活物的形成、凝血酶原的激活和纤维蛋白的生成三个基本步骤。根据凝血酶原激活物形成的途径的不同,血液凝固可分为内源性凝血和外源性凝血。不同的哺乳动物有相同种类的凝血因子并且有高度的同源性,但不同动物的凝血因子含量不同,导致凝血系统功能的检验项目的值有不同。
PT:凝血酶原时间(PT)测定,用于筛查外源性和共同凝血途径的凝血因子(I、II、V、VII、X)的缺乏,同时也是口服华法林治疗的首选监测指标。
APTT:活化部分凝血活酶时间(APTT)测定,用于筛查内源性和共同凝血途径的凝血因子(I、II、V、VIII、IX、X、XI、XII)的缺乏,还可用于凝血因子抑制物的检测(如狼疮抗凝物)以及监测肝素抗凝治疗、血友病患者的凝血因子替代治疗。
TT:凝血酶时间(TT)测定,TT测定结果用来反映FIB减少的指标。
FIB:纤维蛋白原(FIB)含量测定,可用于弥散性血管内凝血和原发性纤溶症、重症肝炎以及低(无)纤维蛋白原血症的筛查。
AT-III:抗凝血酶III的测定,AT-III(AntithrombinIII)又称抗凝血酶(antithrombin,AT),是血浆生理性凝血抑制物中最重要的抗凝物质之一。
本发明采用的试材皆为普通市售品,皆可于市场购得。
下面结合实施例,进一步阐述本发明:
实施例1本发明冻干保护液及质控品的配制
本发明冻干保护液配方:
表1
质控品的配制:
1.分离获得血浆:正常人静脉采集的血液,将血液按与抗凝剂9:1的比例加入抗凝剂(3.8wt%柠檬酸三钠水溶液)。将加入抗凝剂的血液离心30分钟,相对离心力为2000g,小心分离吸取上层血浆,-20℃以下冷冻备用。
2.制备质控品:37℃水浴溶解一定量的冰冻血浆放置于塑料烧杯中,按照保护液:血浆为1:9的体积比添加表1保护液。
对比例1对照质控品配制
对照质控品的保护液配方见表2:
表2
对照质控品配制方法同实施例1。
试验例1稳定性检测。
1.复溶稳定性检测:将实施例1中制备的质控品、对比例1的对照质控品(保护液配方中不含:烟酰胺、氯化镁、氯化锰和蔗糖)和市售质控品以标示体积准确复溶在室温(20~28℃)条件下保存,每4小时取样一次,检测PT、APTT、TT、FIB、AT-III值。检测结果如表3~5所示。结果显示本发明制备的质控品复溶后在室温储存条件下较稳定。
表3本发明质控品复溶稳定性检测结果
表4对照质控品复溶稳定性检测结果
表5市售质控品复溶稳定性检测结果
对检测数据进行线性回归,并对斜率b与0的显著性差异进行双侧t检验,查表可知α=0.05,ν=8,tα(ν)=2.306,P值大于0.05,表明本发明制备的凝血质控品复溶后在室温下储存32小时,PT、APTT、TT、FIB、AT-III检测值的基本不变。而对照质控开瓶复溶后室温储存32小时PT、APTT检测值变化较大不能稳定,说明缺少稳定组分,稳定效果不佳,同时检测市售的来源于人的质控血浆开瓶复溶后室温下32小时PT、APTT、TT、FIB检测值变化较大,这充分证明本发明质控品较稳定。
由此可见,本发明制备的质控品与市售产品相比,具有更好的复溶稳定性,对于医院临床检验科,特别是业务量较小的基层医院,在PT、APTT、TT、FIB、AT-III检测项目的质控工作中,质控品开瓶后保存更长时间,可以减少试剂浪费,降低检测成本,给工作带来方便。
2.长期稳定性检测:将实施例1中制备的质控品冻干品和市售的质控品在2~8℃条件下保存,每3个月取出一瓶准确复溶,检测PT、APTT、TT、FIB、AT-III的值。检测结果如表6~8所示。结果显示本发明制备的质控品冻干品在36个月后仍较稳定,有利于商品化生产。
表6本发明质控品长期稳定性检测结果
表7对照质控品长期稳定性检测结果
表8市售质控品长期稳定性检测结果
对检测数据进行线性回归,并对斜率b与0的显著性差异进行双侧t检验,查表可知α=0.05,ν=11,tα(ν)=2.20,本发明质控品PT、APTT、TT、FIB、AT-III检测结果计算P值均大于0.05,表明本发明制备的质控品在+2~+8℃条件保存36个月基本稳定,长期稳定性较好,有利于商品化生产。
对照质控品在+2~+8℃条件保存36个月PT、APTT、TT检测值变化较大不能稳定,说明缺少稳定组分,稳定效果不佳。
市售质控品在+2~+8℃条件保存36个月,PT、APTT、TT、FIB检测结果出现明显的变化说明不能稳定储存36个月。
以上仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (9)
1.一种血浆保存液,其特征在于,包括:烟酰胺、三羟甲基氨基甲烷、蔗糖、抑肽酶、氯化镁、氯化锰、防腐剂、消泡剂、pH调节剂和水;
各组分含量为:
烟酰胺122.14~244.24g/L、三羟甲基氨基甲烷100~300 mM/L、蔗糖100~ 300g/L、抑肽酶10000~100000KIU/L、氯化镁0.5~5mM、氯化锰0.5~5mM、防腐剂2.5~5.0g/L、消泡剂5~15g/L,采用pH调节剂调节pH至7.0~7.9。
2.根据权利要求1所述的血浆保存液,其特征在于,各组分含量为:
烟酰胺244.24g/L、三羟甲基氨基甲烷200 mM/L、蔗糖200g/L、抑肽酶80000KIU/L、氯化镁1~4mM、氯化锰1~4mM、防腐剂4g/L、消泡剂10g/L,采用pH调节剂调节pH至7.0~7.9。
3.根据权利要求1所述的血浆保存液,其特征在于,所述消泡剂为B-400水性消泡剂、T-2318中的至少一种。
4.根据权利要求1所述的血浆保存液,其特征在于,所述防腐剂为叠氮钠、吡硫钠、庆大霉素中的至少一种。
5.根据权利要求1所述的血浆保存液,其特征在于,所述pH调节剂为盐酸和/或甘氨酸。
6.一种凝血质控品,其特征在于,由权利要求1~5任一项所述的血浆保存液和血浆组成。
7.根据权利要求6所述的凝血质控品,其特征在于,所述血浆保存液和血浆的体积比为(0.05~0.15):(0.85~0.95);所述凝血质控品的PT、APTT、TT、FIB、AT-III值均在正常人凝血指标内。
8.权利要求6或7所述凝血质控品的制备方法,其特征在于,包括:将烟酰胺、三羟甲基氨基甲烷、蔗糖、抑肽酶、氯化镁、氯化锰、防腐剂、消泡剂混合,加入pH调节剂调节pH至7.0~7.9,然后加入血浆,获得凝血质控品。
9.权利要求6或7所述的凝血质控品或权利要求8所述的制备方法制得的凝血质控品,在制备凝血检测试剂中的应用;所述凝血检测的指标包括PT、APTT、TT、FIB、AT-III中至少一种。
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