新型喹诺酮类抗菌药西他沙星注射剂临床前初步研究
发布时间：2018-07-15 07:33
【摘要】：目的：制备西他沙星注射剂，并对其进行制剂学、安全性及药物动力学评价。 方法：(1)建立高效液相色谱法测定西他沙星注射剂中的药物含量及其有关物质，用来评价制备工艺。(2)西他沙星注射剂的处方设计前研究。(3)进行西他沙星注射剂的处方筛选及工艺探索。(4)通过溶血性、过敏反应、血管、肌肉刺激性试验和热原检查对西他沙星注射剂进行初步安全性评价。(5)选用司帕沙星为内标物，建立高效液相色谱法测定大鼠体内西他沙星的含量变化，，初步研究其在大鼠体内药动学特征。 结果：(1)采用HPLC法测定制剂中西他沙星及有关物质的含量，该法快速、灵敏、稳定可靠。(2)西他沙星易溶于酸性水溶液，在高温条件下稳定性良好；对酸、碱、高湿及光照条件敏感，该药物的最稳定pH约为4~6之间。(3)以乳酸为pH调节剂，氯化钠为等渗调节剂成功制备了西他沙星注射剂。制剂工艺为采用0.03%活性炭于煮沸条件下处理30min，灭菌条件为115℃灭菌30min。(4)注射剂经过影响因素、加速、长期试验各指标均符合规定，制剂质量稳定。(5)安全性评价表明，制备的西他沙星注射剂溶血性、过敏反应、血管及肌肉刺激性和热原检查均显阴性。(6)西他沙星注射剂大鼠体内药动学研究表明，药物在大鼠体内t1/2为0.857h，平均滞留时间(MRT)为0.996h，表观分布容积为4.140L·kg-1。 结论：成功建立了西他沙星注射剂的制备方法，并得到良好的初步稳定性及安全性评价结果。西他沙星注射剂的大鼠体内药动学研究结果为进一步研发奠定了良好的基础。
[Abstract]:Objective: to prepare cilafloxacin injection and evaluate its pharmacokinetics and safety. Methods: (1) to establish a high performance liquid chromatography (HPLC) method for the determination of cetafloxacin injection and its related substances. It was used to evaluate the preparation process. (2) Pre-design study on the formulation of cilafloxacin injection. (3) screening of the formulation of cilastacin injection and exploration of the technology. (4) by hemolytic, allergic reaction, blood vessel, blood vessel, Muscle irritation test and pyrogen test were used to evaluate the safety of cisfloxacin injection. (5) using sparfloxacin as internal standard, a high performance liquid chromatography (HPLC) method was established for the determination of cetafloxacin in rats. The pharmacokinetic characteristics in rats were preliminarily studied. Results: (1) the HPLC method was used to determine the content of estracin and its related substances. The method was rapid, sensitive, stable and reliable. (2) ciltafloxacin was easily soluble in acidic aqueous solution and had good stability at high temperature. The most stable pH of the drug was about 4 ~ 6. (3) Cetafloxacin injection was successfully prepared with lactic acid as pH regulator and sodium chloride as isoosmotic regulator. The preparation process was treated with 0.03% activated carbon for 30 min under boiling condition, and sterilizing condition was 115 鈩
本文编号：2123333
[Abstract]:Objective: to prepare cilafloxacin injection and evaluate its pharmacokinetics and safety. Methods: (1) to establish a high performance liquid chromatography (HPLC) method for the determination of cetafloxacin injection and its related substances. It was used to evaluate the preparation process. (2) Pre-design study on the formulation of cilafloxacin injection. (3) screening of the formulation of cilastacin injection and exploration of the technology. (4) by hemolytic, allergic reaction, blood vessel, blood vessel, Muscle irritation test and pyrogen test were used to evaluate the safety of cisfloxacin injection. (5) using sparfloxacin as internal standard, a high performance liquid chromatography (HPLC) method was established for the determination of cetafloxacin in rats. The pharmacokinetic characteristics in rats were preliminarily studied. Results: (1) the HPLC method was used to determine the content of estracin and its related substances. The method was rapid, sensitive, stable and reliable. (2) ciltafloxacin was easily soluble in acidic aqueous solution and had good stability at high temperature. The most stable pH of the drug was about 4 ~ 6. (3) Cetafloxacin injection was successfully prepared with lactic acid as pH regulator and sodium chloride as isoosmotic regulator. The preparation process was treated with 0.03% activated carbon for 30 min under boiling condition, and sterilizing condition was 115 鈩
本文编号：2123333
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