摘要
目的:研制一种兼有抗凝血与抗感染作用的封管用枸橼酸钠注射液。方法:建立体外中心静脉插管仿真装置,用于封管用枸橼酸钠注射液配方及制备工艺的筛选;采用高效液相色谱法测定枸橼酸钠的含量;通过加速试验和长期试验考察该制剂的稳定性;进行体外抗凝试验和抑菌试验的药效学研究;通过溶血性试验和急性毒性试验考察其安全性。结果:本研究制备的封管用枸橼酸钠注射液采用国产原料药以及常规水针剂工艺;该制剂质量可控;在留置导管中可滞留72小时以上;该制剂的使用期限至少为18个月;该制剂的体外抗凝血作用总体上不弱于肝素钠注射液;该制剂对留置导管感染中常见的病原菌具有良好的抑制作用;该制剂无明显溶血现象;小鼠尾静脉给药的半数致死量(LD_(50))为0.305g/kg。结论:本研究研制的封管用枸橼酸钠注射液处方及制备工艺简单,质量稳定,且兼有良好的抗凝与抗感染作用,有望成为新一代的封管液。
Objective: To develop a sodium citrate for catheter locking which has the advantages of anticoagulant and antimicrobial properties. Methods: The imitative setting of indwelling catheter in vitro was established by which the prescription and technics were screened. High performance liquid chromatography was taken to determine the content of citrate in the prescription. Its stability was investigated through accelerated test and long-term test. The anticoagulant effect and the antibacterial activity of the injection were studied in vitro. Its security was investigated by hemolytic test in vitro and the acute toxicity in mice in vivo. Results: The raw material was made in China and the technics of preparation was conventionally taken. The quality of sodium citrate injection for catheter locking could be controlled and the prescription in this research could be remained for at least 72 hours in the retained catheter. The period of validity of the prescription was more than 18 months. Its anticoagulation was better than that of heparin. Sodium citrate injection for catheter locking had favorable antimicrobial efficacy against pathogen accounting for infection of indwelling catheter. The haemolysis and coagulation on red blood cells of rabbits in vitro of the sodium citrate injection were not significant. The median lethal dose (LD50) of sodium citrate injection for catheter locking was 0.305g/kg in mice. Conclusions: The sodium citrate injection for catheter locking prepared in this research, which has the advantages of anticoagulant and antimicrobial properties with simple procedure of preparation and steady characteristics, is a promising substitute for heparin sodium injection.
引文
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