低分子肝素的差掖葱蚂刘建社主任讲稿课件

Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.深静脉栓塞病因学Virchow'striad(1856)血流淤滞血管壁损伤血液失调-“高凝状态"Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.深静脉栓塞病因学Virchow'striad(1856)血流淤滞和高凝状态=深静脉血栓形成的危险性年龄:促使静脉回流的肌肉泵作用缺乏以前有静脉血栓病史静脉功能不足，静脉曲张充血性心衰慢性呼吸衰竭肥胖年龄:血液流变学和凝血系统的改变癌症

手术制动失代偿的充血性心衰近期心肌梗塞中风合并瘫痪炎症感染脱水心肌梗塞肥厚性心肌病肾病综合征患者疾病血流淤滞DVT的危险性高凝状态血管内皮破坏手术感染Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.血流淤滞和高凝状态=深静脉血栓形成的危险性年龄:促Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.生产制造过程肝素的来源盐的性质平均分子量，分子量分布分子链末端的结构抗Xa:IIa活性比值药代动力学，药效学特性临床循证低分子肝素之间的不同点Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.生产制造过程低分子肝素之间的不同点Evaluationon通用名

Dalteparin

Enoxaparin

Nadroparin

Parnaparin*Reviparin

Tinzaparin制造工艺硝酸解聚

肝素苯甲基酯碱性

解聚

硝酸解聚

过氧化氢和铜氧化解聚

硝酸解聚酶法解聚(肝素酶)商品名Fragmin法安明

Clexane克赛

Fraxiparine速碧林

Fluxum栓复欣

Clivarin诺易平LogiparinInnohep盐

钠

钠钙

钠钠钠公司

法玛西亚普强

赛诺菲-安万特

葛兰素

OpocrinKnoll

Novo-NordiskLeo*来源为牛+猪肝素；其他均为猪肝素

降解方法和精确的制造过程决定不同的分子量分布

分子量&解聚方法Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.制造工艺商品名盐公司*来源为牛+猪肝素；其他均为猪肝素

Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.012345678910111204681012%2分子量(kDa)Enoxaparin克赛Nadroparin速碧林Dalteparin法安明15.0%79.0%6.0%5.5%6.5%88.0%0.5%14.0%85.5%EnoxaparinDalteparinNadroparin分子量分布：克赛，速碧林，法安明的比较Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.012345678910111204681012%2分子量Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.克赛1000IU速碧林1000IU法安明1000IU药代动力学：相应剂量下血浆抗Xa活性01.6TinzaparinAUC(IU/ml)1000IU1.0Anti-XaEvaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.克赛1000IU速碧林1000IU法安明100004812162020406080100%Xa抑制率Tinzaparin法安明Ardeparin克赛药代动力学:

100Anti-XaU/kg皮下注射,达峰时间小时Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.04812162020406080100%Xa抑制率TEnoxaparin克赛Nadroparin速碧林Dalteparin法安明小时00.511.522.533.544.5p<0.001p<0.001皮下注射三种不同低分子肝素：

抗Xa活性达峰时间（均值±标准差）Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.EnoxaparinNadroparinDalteparin00.040.080.120.16Enoxaparin克赛Nadroparin速碧林Dalteparin法安明抗XaIU/mlp<0.001p<0.001皮下注射三种不同低分子肝素各1,000抗Xa单位：

最大抗Xa活性（左图）及其曲线下面积（右图）（均值±标准差）克赛速碧林法安明Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.00.040.080.120.16EnoxaparinNad在被批准预防深静脉血栓的剂量下,

各低分子肝素的血浆抗Xa浓度1.02.03.04.005.0半衰期(h)NS2P<0.052P<0.052AUC

(1000IUanti-Xa/ml)01.6P<0.0011P<0.0011P<0.0011Dalteparin5000IUanti-Xa

Enoxaparin40mg(4000IUanti-Xa)

Nadroparin3075IUanti-Xa

Tinzaparin50IUanti-Xa/kg较其他低分子肝素,克赛具有更强及更长的抗Xa抑制作用Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.在被批准预防深静脉血栓的剂量下,

各低分子肝素的血浆抗Xa浓Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.克赛®：广泛的适应证治疗不稳定性心绞痛和Q非波心梗预防血液透析时体外循环

中血栓形成预防深静脉血栓（DVT）形成及肺栓塞心血管骨科血透治疗已经形成的深静脉血栓Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.克赛®：广泛的适应证治疗不稳定性心绞痛预防血液透析时体外循Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.深静脉栓塞病因学Virchow'striad(1856)血流淤滞血管壁损伤血液失调-“高凝状态"Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.深静脉栓塞病因学Virchow'striad(1856)血流淤滞和高凝状态=深静脉血栓形成的危险性年龄:促使静脉回流的肌肉泵作用缺乏以前有静脉血栓病史静脉功能不足，静脉曲张充血性心衰慢性呼吸衰竭肥胖年龄:血液流变学和凝血系统的改变癌症

手术制动失代偿的充血性心衰近期心肌梗塞中风合并瘫痪炎症感染脱水心肌梗塞肥厚性心肌病肾病综合征患者疾病血流淤滞DVT的危险性高凝状态血管内皮破坏手术感染Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.血流淤滞和高凝状态=深静脉血栓形成的危险性年龄:促Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.生产制造过程肝素的来源盐的性质平均分子量，分子量分布分子链末端的结构抗Xa:IIa活性比值药代动力学，药效学特性临床循证低分子肝素之间的不同点Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.生产制造过程低分子肝素之间的不同点Evaluationon通用名

Dalteparin

Enoxaparin

Nadroparin

Parnaparin*Reviparin

Tinzaparin制造工艺硝酸解聚

肝素苯甲基酯碱性

解聚

硝酸解聚

过氧化氢和铜氧化解聚

硝酸解聚酶法解聚(肝素酶)商品名Fragmin法安明

Clexane克赛

Fraxiparine速碧林

Fluxum栓复欣

Clivarin诺易平LogiparinInnohep盐

钠

钠钙

钠钠钠公司

法玛西亚普强

赛诺菲-安万特

葛兰素

OpocrinKnoll

Novo-NordiskLeo*来源为牛+猪肝素；其他均为猪肝素

降解方法和精确的制造过程决定不同的分子量分布

分子量&解聚方法Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.制造工艺商品名盐公司*来源为牛+猪肝素；其他均为猪肝素

Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.012345678910111204681012%2分子量(kDa)Enoxaparin克赛Nadroparin速碧林Dalteparin法安明15.0%79.0%6.0%5.5%6.5%88.0%0.5%14.0%85.5%EnoxaparinDalteparinNadroparin分子量分布：克赛，速碧林，法安明的比较Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.012345678910111204681012%2分子量Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.克赛1000IU速碧林1000IU法安明1000IU药代动力学：相应剂量下血浆抗Xa活性01.6TinzaparinAUC(IU/ml)1000IU1.0Anti-XaEvaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.克赛1000IU速碧林1000IU法安明100004812162020406080100%Xa抑制率Tinzaparin法安明Ardeparin克赛药代动力学:

100Anti-XaU/kg皮下注射,达峰时间小时Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.04812162020406080100%Xa抑制率TEnoxaparin克赛Nadroparin速碧林Dalteparin法安明小时00.511.522.533.544.5p<0.001p<0.001皮下注射三种不同低分子肝素：

抗Xa活性达峰时间（均值±标准差）Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.EnoxaparinNadroparinDalteparin00.040.080.120.16Enoxaparin克赛Nadroparin速碧林Dalteparin法安明抗XaIU/mlp<0.001p<0.001皮下注射三种不同低分子肝素各1,000抗Xa单位：

最大抗Xa活性（左图）及其曲线下面积（右图）（均值±标准差）克赛速碧林法安明Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.00.040.080.120.16EnoxaparinNad在被批准预防深静脉血栓的剂量下,

各低分子肝素的血浆抗Xa浓度1.02.03.04.005.0半衰期(h)NS2P<0.052P<0.052AUC

(1000IUanti-Xa/ml)01.6P<0.0011P<0.0011P<0.0011Dalteparin5000IUanti-Xa

Enoxaparin40mg(4000IUanti-Xa)

Nadroparin3075IUanti-Xa

Tinzaparin50IUanti-Xa/kg较其他低分子肝素,克赛具有更强及更长的抗Xa抑制作用Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.在被批准预防深静脉血栓的剂量下,

各低分子肝素的血浆抗Xa浓Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.Evaluationonly.Create