低分子肝素的差掖蔥螞-劉建社主任講稿

Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.深靜脈栓塞病因?qū)WVirchow'striad(1856)血流淤滯血管壁損傷血液失調(diào)-“高凝狀態(tài)"Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.血流淤滯和高凝狀態(tài)=深靜脈血栓形成的危險性年齡:促使靜脈回流的肌肉泵作用缺乏以前有靜脈血栓病史靜脈功能不足，靜脈曲張充血性心衰慢性呼吸衰竭肥胖年齡:血液流變學和凝血系統(tǒng)的改變癌癥

手術(shù)制動失代償?shù)某溲孕乃ソ谛募」Ｈ酗L合并癱瘓炎癥感染脫水心肌梗塞肥厚性心肌病腎病綜合征患者疾病血流淤滯DVT的危險性高凝狀態(tài)血管內(nèi)皮破壞手術(shù)感染Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.生產(chǎn)制造過程肝素的來源鹽的性質(zhì)平均分子量，分子量分布分子鏈末端的結(jié)構(gòu)抗Xa:IIa活性比值藥代動力學，藥效學特性臨床循證低分子肝素之間的不同點Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.通用名

Dalteparin

Enoxaparin

Nadroparin

Parnaparin*Reviparin

Tinzaparin制造工藝硝酸解聚

肝素苯甲基酯堿性

解聚

硝酸解聚

過氧化氫和銅氧化解聚

硝酸解聚酶法解聚(肝素酶)商品名Fragmin法安明

Clexane克賽

Fraxiparine速碧林

Fluxum栓復欣

Clivarin諾易平LogiparinInnohep鹽

鈉

鈉鈣

鈉鈉鈉公司

法瑪西亞普強

賽諾菲-安萬特

葛蘭素

OpocrinKnoll

Novo-NordiskLeo*來源為牛+豬肝素；其他均為豬肝素

降解方法和精確的制造過程決定不同的分子量分布

分子量&解聚方法Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.012345678910111204681012%2分子量(kDa)Enoxaparin克賽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：克賽，速碧林，法安明的比較Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.克賽1000IU速碧林1000IU法安明1000IU藥代動力學：相應劑量下血漿抗Xa活性01.6TinzaparinAUC(IU/ml)1000IU1.0Anti-XaEvaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.04812162020406080100%Xa抑制率Tinzaparin法安明Ardeparin克賽藥代動力學:

100Anti-XaU/kg皮下注射,達峰時間小時Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Enoxaparin克賽Nadroparin速碧林Dalteparin法安明小時00.511.522.533.544.5p<0.001p<0.001皮下注射三種不同低分子肝素：

抗Xa活性達峰時間（均值±標準差）Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.00.040.080.120.16Enoxaparin克賽Nadroparin速碧林Dalteparin法安明抗XaIU/mlp<0.001p<0.001皮下注射三種不同低分子肝素各1,000抗Xa單位：

最大抗Xa活性（左圖）及其曲線下面積（右圖）（均值±標準差）克賽速碧林法安明Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.在被批準預防深靜脈血栓的劑量下,

各低分子肝素的血漿抗Xa濃度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較其他低分子肝素,克賽具有更強及更長的抗Xa抑制作用Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.克賽?：廣泛的適應證治療不穩(wěn)定性心絞痛和Q非波心梗預防血液透析時體外循環(huán)

中血栓形成預防深靜脈血栓（DVT）形成及肺栓塞心血管骨科血透治療已經(jīng)形成的深靜脈血栓Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright2004-2011AsposePtyLtd.Evaluationonly.CreatedwithAspose.Slidesfor.NET3.5ClientProfile.Copyright200