一次性塑料血袋中还原物质的分析及其安全性研究

【作者】 付步芳；

【导师】 奚廷斐；

【作者基本信息】 中国药品生物制品检定所 ， 药物分析， 2007， 硕士

【摘要】 一次性塑料血袋在贮存和使用过程中，血袋袋体中的小分子有机物(主要是还原物质)会析出到保存液或血液制品中，影响血液制品的质量和输血安全，因此血袋中的还原物质必须严格控制。国标GB14232.1—2004／ISO3826—1：2004中已经对还原物质的总量作了限制，但仍不足以说明还原物质的安全性，血袋中还原物质的组成状况尚未见有文献报道。血袋中析出的一些痕量的有毒的小分子有机物对还原物质的总量指标贡献很小，但危害却很大，对血液质量和被输血者存在潜在威胁，因此只控制还原物质的总量是不够的。本文分析了血袋中还原物质的组成，并对其安全性做出了初步评价。在还原物质的分析方面，本文采用间接碘量滴定法测定了不同血袋样品的还原物质总量，从血袋的生产厂家(配方、工艺)、类型及储存稳定性(保存温度、时间)方面考察了还原物质的变化规律。结果表明，血袋袋体材料的配方及工艺是影响还原物质总量的主要因素；提高保存温度，还原物质的总量增加；全血袋的还原物质总量最高，其次是转移袋和未灭菌袋；血袋的还原物质总量随保存时间增加而缓慢增加。同时本文还探索了合适的SPE／GC／MS条件，用该法可以很好地鉴定出一次性塑料血袋水浸提液、保存液、袋装全血中的还原物质。结果发现，水浸提液中的还原物质主要是一些酯类和烷烃，保存液中极性较强的醇类含量较高，而袋装全血中仅检测到烷烃和较高含量的邻苯二甲酸二(2-乙基)己酯(DEHP)。在还原物质的安全性评价方面，从血液质量的变化，溶血性能，凝血及补体性能的变化来考察还原物质含量不同的血袋的血液相容性。结果表明，还原物质对白细胞、血小板及总补体CH50有一定的破坏作用；血液中钾离子浓度和游离血红蛋白随还原物质的增加而增加；而还原物质对溶血率、红细胞、Na~+浓度、pH、补体C3、C4、凝血指标PT和Fbg的影响不明显。同时本文采用MTT法考察了还原物质含量不同的血袋的细胞毒性，结果表明，血袋材料的细胞毒性与其还原物质的总量呈明显的正相关性。还原物质的总量、种类及每种还原物质的含量都会影响其安全性。更多还原

【Abstract】 Small molecular compounds (reducing substances) will release from blood bag materials into anticoagulants or blood products during the time of plastic blood bags reserved or used, which will have a negative effect on blood products and donee. So reducing substances of plastic blood bags must be strictly controlled. GB14232.1 -2004/ISO3826-1:2004 has limits the total amounts of reducing substances, but it is not adequate to illuminate the ponderance of reducing substances. The composing determination of reducing substances released from plastic blood bags hasn’t been reported by literatures. Some trace poisonous small molecular compounds released from blood bag materials contribute little to the total amounts of reducing substances, but they do potential harm to blood products and donee. This paper analyzed the composing of reducing substances and had a primary safety assessment on them.At the aspect of reducing substances analysis, the total amounts of reducing substances released from different type blood bags were determined by indirect iodimetry. This paper researched the reducing substances’ changing rules. The result indicated that factors such as prescription, craft, type, temperature, time, et al, had different affection on total amounts of reducing substances released from plastic blood bags. Prescription and craft of blood bag materials were the basical factors of affecting the total amounts of reducing substances. Reducing substances would increase as reserving temperature heightened. The reducing substances released from whole blood bags were much more than those released from translation bags and non-sterilized bags. Reducing substances would increase as reserving time prolonged. The composing of reducing substances was determined by SPE/GC/MS released into plastic blood bags aqueous extract, anticoagulant and whole blood. The result indicated that esters and alkanes were the main reducing substances in aqueous extract, polar alcohols had high amounts in anticoagulant, while only alkanes and a great deal of DEHP were determined in whole blood.At the aspect of safety assessment of reducing substances, haemocompatibility was investigated by testing blood quality, haemolysis, blood coagulation, complement. The result indicated that reducing substances could destroyed white blood cells, blood platelets and CH50. The concentration of K~+ and free hemoglobin in whole blood would increase quickly as reducing substances increased. But reducing substances had little effect on haemolysis, red blood cells, the concentration of Na~+, pH, complement of C3, C4, PT, Fbg. Cytotoxicity was determined by the method of MTT. The result indicated that cytotoxicity of blood bags materials had positive correlation with their total amounts of reducing substances.更多还原