肝素类抗凝药物的作用机制及发展.pptVIP

肝素类抗凝药物作用机制及发展 首都医科大学同仁医院心脏中心 史旭波 普通肝素的发现 2000万人/年使用肝素 1916年 Mclean fat oluble substances, from liver tissues that inhibited blood coagulation McLean, The thaoanooplastc action f cephalin, An. Ph sin. I gt6, 4i, 15-i. McLean inin tront of the Coh m bus athleticChub. 4.W.H. Howell and E Hot, Two new factors in blod comagnilabion-heparin and 肝素的制备 Combine 5,000 lbs intestines, 200 gallons water, 10 gallons ii, and 5 gallons甲苯. Hold at90°Ffor17 hours Add 30 gallons acetic acid, 35 gallons ammonia, sodium hydroxide to adjust pH, and 235 gallons water. Bring to a boil; then filter. Add 200 gallons hot water to filtrate and allow to stand overnight, then skim if the fat Keep pancreatic extract at 100 F for three days, then bring to boil Filter solids and assay for heparin content. Courtesy of Neil Kleiman 肝素的首次临床应用 1938, Dr. Wright first treated a patient of thrombophlebitis with an experimenta natural anticoagulant called heparin, isolated from animal organs. The condition of Dr. Wrights patient improved in two weeks 1960.Dr. Wright received素有“美国诺贝尔奖”之称的美国一亚伯雷斯克奖from he American Heart Association for his study of the use of anticoagulants 肝素作用机制的研究历程 1968-73肝素通过AT发挥作用(肝素纯化凝血瀑布) 1976 只有部分肝素分子能与AT结合(30-50%) 1976 抗1活性与月分子长度有关 抗Xa活性与肝素分子长度无关 量肝素发