尖吻蝮蛇凝血酶在大鼠体内的药代动力学
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摘要
尖吻蝮蛇凝血酶是从尖吻蝮蛇蛇毒中分离纯化得到的一种类凝血酶,是本团队研发的止血一类新药。采用125Ⅰ-标记的放射性同位素法和三氯醋酸沉淀结合放射性检测法研究尖吻蝮蛇凝血酶在大鼠体内的药代动力学。结果表明两种方法测定的AUC值与剂量均呈正相关,相关系数分别为0.999 8和0.999 0;肝、脾、心在给药后5 min药物含量最高,其他绝大部分组织在给药后30 min药物含量最高,以后逐渐降低;在各时间点,肝组织含药量显著高于其他组织;此外,尖吻蝮蛇凝血酶排泄较完全,主要由尿排泄。
Haemocoagulase Acutus( Halase),a new hemostatic in halase development,is a high-performance thrombin-like enzyme( TLE) derived from snake venom of Agkistrodon acutus. To study the pharmacokinetics of Halase,~(125)Ⅰ-labeled radioisotope method and radioassay combined with TCA precipitate were applied in rats. Results showed that AUC values were positively correlated with doses under both used methods,and the correlation coefficients were 0. 999 8 and 0. 999 0 respectively; drug concentration in liver,spleen and heart reached its peak after 5 minutes of administration while most of other organs reached it in 30 minutes,and then gradually decreased; in each time point,drug concentration in the liver was significantly higher than that in other tissues; Halase was completely excreted and mainly in urine.
Haemocoagulase Acutus( Halase),a new hemostatic in halase development,is a high-performance thrombin-like enzyme( TLE) derived from snake venom of Agkistrodon acutus. To study the pharmacokinetics of Halase,~(125)Ⅰ-labeled radioisotope method and radioassay combined with TCA precipitate were applied in rats. Results showed that AUC values were positively correlated with doses under both used methods,and the correlation coefficients were 0. 999 8 and 0. 999 0 respectively; drug concentration in liver,spleen and heart reached its peak after 5 minutes of administration while most of other organs reached it in 30 minutes,and then gradually decreased; in each time point,drug concentration in the liver was significantly higher than that in other tissues; Halase was completely excreted and mainly in urine.
引文
[1]吴忠.尖吻蝮蛇凝血酶用作出血性疾病的药物:中国,CN1218747[P].2003-08-14.
[2]吴忠.止血一类新药Halase的药效学研究[J].中药材,2005,28(2):125-128.WU Zhong.The pharmacodynamics study of a new hemostatic Halase[J].Journal of Chinese Medicinal Materials,2005,28(2):125-128.
[3]苏薇薇.止血一类新药Halase的长期毒性试验[J].中药材,2005,28(3):211-212.SU Weiwei.The long-term toxicity test of a new hemostatic Halase[J].Journal of Chinese Medicinal Materials,2005,28(3):211-212.
[4]吴忠.止血一类新药Halase的一般药理学研究[J].中药材,2005,28(4):326-327.WU Zhong.The general pharmacological study of a new hemostatic Halase[J].Journal of Chinese Medicinal Materials,2005,28(4):326-327.
[5]邓沁,吴忠,彭维,等.尖吻蝮蛇凝血酶分离纯化新工艺研究[J].中山大学学报(自然科学版),2016,55(6):161-164.DENG Qin,WU Zhong,PENG Wei,et al.New process for separation and purification of Haemocoagulase Acutus[J].Acta Scientiarum Naturalium Universitatis Sunyatseni,2016,55(6):161-164.
[6]邓沁,吴忠,苏薇薇,等.一类新药尖吻蝮蛇凝血酶对SD大鼠围产期生殖毒性试验[J].中南药学,2017,15(6):730-734.DENG Qin,WU Zhong,SU Weiwei,et al.Perinatal reproductive toxicity of Halase in perinatal Sprague-Dawley rats[J].Central South Pharmacy,2017,15(6):730-734.
[2]吴忠.止血一类新药Halase的药效学研究[J].中药材,2005,28(2):125-128.WU Zhong.The pharmacodynamics study of a new hemostatic Halase[J].Journal of Chinese Medicinal Materials,2005,28(2):125-128.
[3]苏薇薇.止血一类新药Halase的长期毒性试验[J].中药材,2005,28(3):211-212.SU Weiwei.The long-term toxicity test of a new hemostatic Halase[J].Journal of Chinese Medicinal Materials,2005,28(3):211-212.
[4]吴忠.止血一类新药Halase的一般药理学研究[J].中药材,2005,28(4):326-327.WU Zhong.The general pharmacological study of a new hemostatic Halase[J].Journal of Chinese Medicinal Materials,2005,28(4):326-327.
[5]邓沁,吴忠,彭维,等.尖吻蝮蛇凝血酶分离纯化新工艺研究[J].中山大学学报(自然科学版),2016,55(6):161-164.DENG Qin,WU Zhong,PENG Wei,et al.New process for separation and purification of Haemocoagulase Acutus[J].Acta Scientiarum Naturalium Universitatis Sunyatseni,2016,55(6):161-164.
[6]邓沁,吴忠,苏薇薇,等.一类新药尖吻蝮蛇凝血酶对SD大鼠围产期生殖毒性试验[J].中南药学,2017,15(6):730-734.DENG Qin,WU Zhong,SU Weiwei,et al.Perinatal reproductive toxicity of Halase in perinatal Sprague-Dawley rats[J].Central South Pharmacy,2017,15(6):730-734.