CN116656661A - 一种稳定而准确的复合生化校准品及其制备方法 - Google Patents

一种稳定而准确的复合生化校准品及其制备方法 Download PDF

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CN116656661A
CN116656661A CN202310637942.XA CN202310637942A CN116656661A CN 116656661 A CN116656661 A CN 116656661A CN 202310637942 A CN202310637942 A CN 202310637942A CN 116656661 A CN116656661 A CN 116656661A
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李金英
张发勇
徐业朝
王丽
邹志良
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Hebei Aioulu Biotechnology Co ltd
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Abstract

本发明公开了一种稳定而准确的复合生化校准品及其制备方法，属于生化诊断医疗领域。本发明稳定而准确的复合生化校准品，包括：基本材料和添加物质，具备明确的目标浓度。校准品成分合理，不添加人源血清，解决了复合校准品中添加人源血清基质带来的传染病风险；具备长时间稳定性，解决了复合校准品中各种酶类的长期储存不稳定的问题，避免了临床的基质效应，储存有效期长，极大的方便了临床的使用。本发明公开了一种稳定而准确的复合生化校准品制备方法，制备过程准确，采用多中心，多实验室按照国际溯源要求，对校准品进行赋值，使得赋值更准确规范。

Description

一种稳定而准确的复合生化校准品及其制备方法
技术领域
本发明涉及一种稳定而准确的复合生化校准品及其制备方法，属于生化诊断医疗领域。
背景技术
生化试剂在临床应用已经普及，国产生化试剂替代进口品牌已经大势所趋，但和生化试剂配套的校准品相对落后。由于的法律规定、复合校准品校准项目多、添加物质复杂、定值更困难等原因，现阶段通常使用英国朗道，美国伯乐和瑞士罗氏校准定标进行校准，国内生产校准品厂家大多是直接购买这些厂家的半成品分装。国内中生北控生物科技股份有限公司可以生产复合校准品，但是产值较少。其他厂家要么不能生产，要么生产的校准品测试项目不全，或定值不准，或稳定性差导致无法实现临床使用。国产生化试剂在生产、存储、赋值各阶段存在制约因素。
在生产阶段，材料的供应和性质制约了生产。由于国内不允许商品流通人源血清，任何人不得买卖人源血清，血站只提供科研用血清，市场需要获得人源血清只能从国外进口，生产用血清需求量大，进口限制了国内复合校准品的生产，生产的复合校准品如果不含人源血清，可能在临床检测过程中出现基质效应。单纯的总胆红素不溶解于水基质，溶解于氯仿，但氯仿加入后又会破坏血清里面蛋白质。直接胆红素见光分解，在生产和储存过程中都容易导致最终值的变化。
在储存阶段，复合校准品种繁多，酶类物质具有活性，不同离子有的会抑制酶活性，如何在长时间储存过程中保证酶活性和项目与项目之间不互相影响也是一个问题，一旦储存过程中，物质性能下降，整批次校准品就失去了校准的意义。
在赋值阶段：赋值过程要使用不同参考方法，采用不同赋值程序，需要不同实验室多中心进行赋值。单一中心赋值会导致由于仪器、环境、人员等因素导致的系统误差的不确定性。
发明内容
(一)发明目的
本发明的目的是提供一种稳定而准确的复合生化校准品及其制备方法，采用不含人源血清的基质材料，制备校准品，克服复合校准品不稳定、项目不全、测量值不准确、长期储存不稳定的问题。
(二)技术方案
为解决上述问题，本申请的第一方面提供了一种稳定而准确的复合生化校准品，其原料含有如下组分：
在1升纯化水里面含有基本材料：
磷酸二氢钾0.24g/L 磷酸氢二钠1.44g/L 氯化钠8g/L
氯化钾0.2g/L 牛血清白蛋白50g/L 蔗糖150g/L
三磷酸腺苷0.5g/L 液体生物防腐剂1g/L
在1升纯化水里面添加物质及目标浓度：
根据本申请的另一个方面，提供了一种稳定而准确的复合生化校准品制备方法，制造一种稳定而准确的复合生化校准品，包括如下步骤：
S1：在1升纯化水里添加基本材料：磷酸二氢钾0.24g/L、磷酸氢二钠1.44g/L、氯化钠8g/L、氯化钾0.2g/L、牛血清白蛋白50g/L、蔗糖150g/L、三磷酸腺苷0.5g/L、液体生物防腐剂1g/L，将上述基质溶液进行无菌消毒，冷却；
S2：取900毫升基质溶液，测试白蛋白、总蛋白、镁、血清铁、氯、无机磷、钙、二氧化碳的初始值，依据目标浓度计算碳酸氢钠、胆酸钠、缀合胆红素、氯化钙、胆固醇、肌酐、葡萄糖、血清铁、硫酸镁、甘油三酯、尿素、尿酸、氯化钠、磷酸氢二钠每种物质所需添加量，并依次添加，在2～8℃环境中静止24小时；
S3：添加100毫升的新鲜牛血清，静置1小时过滤；
S4：测试白蛋白、总蛋白、镁、血清铁、氯、无机磷、钙、二氧化碳、胆汁酸、总胆红素、直接胆红素、胆固醇、甘油三酯、尿素、尿酸、肌酐、葡萄糖、碱性磷酸酶、丙氨酸氨基转移酶、淀粉酶、天门冬氨酸氨基转移酶、胆碱酯酶、肌酸激酶、Y-谷氨酰转移酶、乳酸脱氢酶、脂肪酶、羟丁酸脱氢酶在溶液中的值，依据目标浓度计算牛血清白蛋白、碱性磷酸酶、丙氨酸氨基转移酶、淀粉酶、天门冬氨酸氨基转移酶、胆碱酯酶、肌酸激酶、谷氨酰转移酶、乳酸脱氢酶、脂肪酶、羟丁酸脱氢酶每种物质所需添加量，并依次添加，定容到1升；
S5：再次测试白蛋白、总蛋白、镁、血清铁、氯、无机磷、钙、二氧化碳、胆汁酸、总胆红素、直接胆红素、胆固醇、甘油三酯、尿素、尿酸、肌酐、葡萄糖、碱性磷酸酶、丙氨酸氨基转移酶、淀粉酶、天门冬氨酸氨基转移酶、胆碱酯酶、肌酸激酶、Y-谷氨酰转移酶、乳酸脱氢酶、脂肪酶、羟丁酸脱氢酶在溶液中的值，微量调整各物质含量使其达到目标浓度；
S6：搅拌均匀，用西林瓶进行分装，在-80℃冻干，按照《体外诊断医疗器械生物样品中量的测量校准品和控制物质赋值的计量学溯源性》要求进行溯源赋值。
(三)有益效果
本发明的上述技术方案具有如下有益的技术效果：
1.符合国内生产要求，不添加人源血清，解决了复合校准品中添加人源血清基质带来的传染病风险；
2.解决了复合校准品中各种酶类的长期储存不稳定的问题，避免了临床的基质效应，储存有效期长，极大的方便了临床的使用；
3.采用多中心，多实验室，按照国际溯源要求，对校准品进行赋值使得赋值更准确规范。
本发明的稳定而准确的复合生化校准品制备过程不依赖于人源血清的使用，适合国内工业化大规模生产。
附图说明
图1是本申请实施例的制备方法流程图。
具体实施方式
为使本申请的目的、技术方案和优点更加清楚明了，下面结合具体实施方式并参照附图，对本申请进一步详细说明。应该理解，这些描述只是示例性的，而并非要限制本申请的范围。此外，在以下说明中，省略了对公知结构和技术的描述，以避免不必要地混淆本申请的概念。
本申请公开了一种稳定而准确的复合生化校准品及其制备方法，以下分别详细说明。
图1是本申请实施例的制备方法流程图。
实施例一
请参照图1，一种稳定而准确的复合生化校准品，其原料含有如下组分：
在1升纯化水里面含有基本材料：
磷酸二氢钾0.24g/L 磷酸氢二钠1.44g/L 氯化钠8g/L
氯化钾0.2g/L 牛血清白蛋白50g/L 蔗糖150g/L
三磷酸腺苷0.5g/L 液体生物防腐剂1g/L
在1升纯化水里面添加物质及目标浓度：
一种稳定而准确的复合生化校准品制备方法，制造一种稳定而准确的复合生化校准品，包括如下步骤：
S1：在1升纯化水里添加基本材料：磷酸二氢钾0.24g/L、磷酸氢二钠1.44g/L、氯化钠8g/L、氯化钾0.2g/L、牛血清白蛋白50g/L、蔗糖150g/L、三磷酸腺苷0.5g/L、液体生物防腐剂1g/L，将上述基质溶液进行无菌消毒，冷却；
S2：取900毫升基质溶液，测试白蛋白、总蛋白、镁、血清铁、氯、无机磷、钙、二氧化碳的初始值，依据目标浓度计算碳酸氢钠、胆酸钠、缀合胆红素、氯化钙、胆固醇、肌酐、葡萄糖、血清铁、硫酸镁、甘油三酯、尿素、尿酸、氯化钠、磷酸氢二钠每种物质所需添加量，并依次添加，在2～8℃环境中静止24小时；
S3：添加100毫升的新鲜牛血清，静置1小时过滤；
S4：测试白蛋白、总蛋白、镁、血清铁、氯、无机磷、钙、二氧化碳、胆汁酸、总胆红素、直接胆红素、胆固醇、甘油三酯、尿素、尿酸、肌酐、葡萄糖、碱性磷酸酶、丙氨酸氨基转移酶、淀粉酶、天门冬氨酸氨基转移酶、胆碱酯酶、肌酸激酶、Y-谷氨酰转移酶、乳酸脱氢酶、脂肪酶、羟丁酸脱氢酶在溶液中的值，依据目标浓度计算牛血清白蛋白、碱性磷酸酶、丙氨酸氨基转移酶、淀粉酶、天门冬氨酸氨基转移酶、胆碱酯酶、肌酸激酶、谷氨酰转移酶、乳酸脱氢酶、脂肪酶、羟丁酸脱氢酶每种物质所需添加量，并依次添加，定容到1升；
S5：再次测试白蛋白、总蛋白、镁、血清铁、氯、无机磷、钙、二氧化碳、胆汁酸、总胆红素、直接胆红素、胆固醇、甘油三酯、尿素、尿酸、肌酐、葡萄糖、碱性磷酸酶、丙氨酸氨基转移酶、淀粉酶、天门冬氨酸氨基转移酶、胆碱酯酶、肌酸激酶、Y-谷氨酰转移酶、乳酸脱氢酶、脂肪酶、羟丁酸脱氢酶在溶液中的值，微量调整各物质含量使其达到目标浓度；
S6：搅拌均匀，用西林瓶进行分装，在-80℃冻干，按照《体外诊断医疗器械生物样品中量的测量校准品和控制物质赋值的计量学溯源性》要求进行溯源赋值。
所制备的复合生化校准品性能稳定、项目齐全、测量值准确、长期储存很稳定。
应当理解的是，本发明的上述具体实施方式仅仅用于示例性说明或解释本发明的原理，而不构成对本发明的限制。因此，在不偏离本发明的精神和范围的情况下所做的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。此外，本发明所附权利要求旨在涵盖落入所附权利要求范围和边界、或者这种范围和边界的等同形式内的全部变化和修改例。

Claims (2)

1.一种稳定而准确的复合生化校准品，其特征在于，其原料含有如下组分：
在1升纯化水里面含有基本材料：
磷酸二氢钾0.24g/L磷酸氢二钠1.44g/L氯化钠8g/L
氯化钾0.2g/L牛血清白蛋白50g/L蔗糖150g/L
三磷酸腺苷0.5g/L液体生物防腐剂1g/L
在1升纯化水里面添加物质及目标浓度：
2.一种稳定而准确的复合生化校准品制备方法，制造权利要求1所述的生化校准品，其特征在于，包括如下步骤：
S1：在1升纯化水里添加基本材料：磷酸二氢钾0.24g/L、磷酸氢二钠1.44g/L、氯化钠8g/L、氯化钾0.2g/L、牛血清白蛋白50g/L、蔗糖150g/L、三磷酸腺苷0.5g/L、液体生物防腐剂1g/L，将上述基质溶液进行无菌消毒，冷却；
S2：取900毫升基质溶液，测试白蛋白、总蛋白、镁、血清铁、氯、无机磷、钙、二氧化碳的初始值，依据目标浓度计算碳酸氢钠、胆酸钠、缀合胆红素、氯化钙、胆固醇、肌酐、葡萄糖、血清铁、硫酸镁、甘油三酯、尿素、尿酸、氯化钠、磷酸氢二钠每种物质所需添加量，并依次添加，在2～8℃环境中静止24小时；
S3：添加100毫升的新鲜牛血清，静置1小时过滤；
S4：测试白蛋白、总蛋白、镁、血清铁、氯、无机磷、钙、二氧化碳、胆汁酸、总胆红素、直接胆红素、胆固醇、甘油三酯、尿素、尿酸、肌酐、葡萄糖、碱性磷酸酶、丙氨酸氨基转移酶、淀粉酶、天门冬氨酸氨基转移酶、胆碱酯酶、肌酸激酶、Y-谷氨酰转移酶、乳酸脱氢酶、脂肪酶、羟丁酸脱氢酶在溶液中的值，依据目标浓度计算牛血清白蛋白、碱性磷酸酶、丙氨酸氨基转移酶、淀粉酶、天门冬氨酸氨基转移酶、胆碱酯酶、肌酸激酶、谷氨酰转移酶、乳酸脱氢酶、脂肪酶、羟丁酸脱氢酶每种物质所需添加量，并依次添加，定容到1升；
S5：再次测试白蛋白、总蛋白、镁、血清铁、氯、无机磷、钙、二氧化碳、胆汁酸、总胆红素、直接胆红素、胆固醇、甘油三酯、尿素、尿酸、肌酐、葡萄糖、碱性磷酸酶、丙氨酸氨基转移酶、淀粉酶、天门冬氨酸氨基转移酶、胆碱酯酶、肌酸激酶、Y-谷氨酰转移酶、乳酸脱氢酶、脂肪酶、羟丁酸脱氢酶在溶液中的值，微量调整各物质含量使其达到目标浓度；
S6：搅拌均匀，用西林瓶进行分装，在-80℃冻干，按照《体外诊断医疗器械生物样品中量的测量校准品和控制物质赋值的计量学溯源性》要求进行溯源赋值。
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3728226A (en) * 1970-06-01 1973-04-17 Baxter Laboratories Inc Blood serum analytical control standard
US5496716A (en) * 1989-10-31 1996-03-05 Abbott Laboratories Stabilized creative kinase MB composition
CN102115737A (zh) * 2009-12-31 2011-07-06 深圳迈瑞生物医疗电子股份有限公司 稳定碱性磷酸酶或其标记物的试剂和方法
CN111909922A (zh) * 2020-06-28 2020-11-10 浙江清华长三角研究院 一种高稳定性的肌酸激酶保护基质
CN113049839A (zh) * 2019-12-27 2021-06-29 桂林英美特生物技术研究所 一种稳定的肝功能类复合质控品
CN113092746A (zh) * 2020-04-30 2021-07-09 北京九强生物技术股份有限公司 生化校准物质

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3728226A (en) * 1970-06-01 1973-04-17 Baxter Laboratories Inc Blood serum analytical control standard
US5496716A (en) * 1989-10-31 1996-03-05 Abbott Laboratories Stabilized creative kinase MB composition
CN102115737A (zh) * 2009-12-31 2011-07-06 深圳迈瑞生物医疗电子股份有限公司 稳定碱性磷酸酶或其标记物的试剂和方法
CN113049839A (zh) * 2019-12-27 2021-06-29 桂林英美特生物技术研究所 一种稳定的肝功能类复合质控品
CN113092746A (zh) * 2020-04-30 2021-07-09 北京九强生物技术股份有限公司 生化校准物质
CN111909922A (zh) * 2020-06-28 2020-11-10 浙江清华长三角研究院 一种高稳定性的肌酸激酶保护基质

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