是谁发现了肝素?答案超乎你想象

2015-06-26 伊文 心在线

肝素,作为抗栓治疗的先驱,其问世及发展充满了戏剧性。从最初发现肝素到人工合成戊糖上市,期间经历了将近百年的时间,这其中有意外和戏剧性的一幕,但更多充满了艰辛、努力和智慧。这些效果更佳、安全性更好的药物,为缓解患者病痛带来了更多希望。肝素,作为抗栓治疗的先驱,其问世及发展充满了戏剧性。如同许多伟大的发现一样,肝素也是在不经意间被人发现和认识的。随着对肝

肝素,作为抗栓治疗的先驱,其问世及发展充满了戏剧性。从最初发现肝素到人工合成戊糖上市,期间经历了将近百年的时间,这其中有意外和戏剧性的一幕,但更多充满了艰辛、努力和智慧。这些效果更佳、安全性更好的药物,为缓解患者病痛带来了更多希望。

肝素,作为抗栓治疗的先驱,其问世及发展充满了戏剧性。如同许多伟大的发现一样,肝素也是在不经意间被人发现和认识的。随着对肝素抗凝机制的研究不断深入,多种低分子量肝素(LMWH)和更新型的人工合成药物被不断开发出来,期间历经几十年,发展之路崎岖不平。

发现肝素

1916年,在约翰·霍普金斯医院工作的二年级医学生麦克廉(Jay McLean)在生理学教授豪维尔(W. H. Howell)的指导下,进行体内促凝血物质效价测定的专题研究。在研究中,麦克廉发现,多种组织(脑、心、肝等)的提取物有促凝作用,而且在贮存期间活性减低。

可是,出乎意料之外的是,贮存最久的肝脏提取物不但不促凝,反而可阻止血液凝固。麦克廉将此发现向豪维尔教授报告,当时豪维尔表示怀疑,怀疑提取物被盐污染。但随后经重复实验证明,肝脏提取物中确实存在一种强力的抗凝物质。豪维尔教授随后从犬肝脏中萃取出该物质。当时认为该物质只存在于肝脏,故取名为肝素,此名称一直沿用至今。起初,由于价格昂贵,肝素仅用于实验。

时间来到20多年后,1937年,加拿大查斯发现,人体的许多组织含有肝素,尤其是肺脏,其含量比肝脏还多。查斯从动物的肺组织提取物中分离并纯化出肝素。自从有了从牛肺组织中提取肝素的技术,才有了肝素的大规模生产。

1938年,研究者开展了第一项肝素预防深静脉血栓形成(DVT)的临床试验,肝素预防血栓形成获得成功。在被发现20多年后,肝素才正式成为预防血栓栓塞的手段,开始广泛应用。自此,肝素成为临床上常用的抗凝药。

获得LMWH

自从20世纪30年代肝素开始用于临床,经过几十年的基础和临床研究,人们对肝素的抗凝作用机制有了更深刻的认识,这为开发LMWH提供了理论依据。

20世纪30年代,Brinkhous及其同事证实,肝素抗凝活性的激活需要一种血浆辅助因子。1968年,Abildgaard将这种因子命名为抗凝血酶III,现在称为抗凝血酶(AT)。

1976年,研究发现,普通肝素的抗凝活性只与其分子中能与AT形成复合物的一小段结构有关。根据这一理论,1978年,法国Choay研究所发明了全球第一个LMWH。

LMWH是由普通肝素经物理、化学或酶解聚方法而获得,分子量在3000——8000之间,具有较肝素更优的抗血栓活性,且与肝素相比,其生物利用度高,半衰期长,抗凝效果可以预测且无需实验室监测,出血副作用少,故其适应证不断扩大,临床应用不断增多。

人工合成戊糖

随着对肝素抗凝机制的研究不断深入,研究者分离出肝素片段中与AT高度亲和的片段,并进一步证明,天然戊糖中含有与肝素和AT高度亲和片段相同的序列。经过大量的基础研究,最终人工合成出改良结构的戊糖,即目前临床使用的磺达肝癸钠。

人工合成的磺达肝癸钠与AT的亲和力较天然戊糖更强,可以更强效地抑制Xa因子,起效更迅速,作用更持久,安全性也更佳。

从最初发现肝素到人工合成戊糖上市,期间经历了将近百年的时间,这其中有意外和戏剧性的一幕,但更多充满了艰辛、努力和智慧。这些效果更佳、安全性更好的药物,为缓解患者病痛带来了更多希望。

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    2015-07-09 飞翔9899

    长见识了

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    2015-06-28 summer474cn

    0

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    2015-06-28 summer474cn

    0

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    2015-06-28 summer474cn

    0

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    2015-06-28 summer474cn

    0

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    2015-06-28 summer474cn

    0

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    2015-06-28 summer474cn

    0

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    2015-06-27 18619c0a62m

    (⊙o⊙)

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=31807, encodeId=ce8f3180e07, content=长见识了, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=01621631568, createdName=飞翔9899, createdTime=Thu Jul 09 11:34:00 CST 2015, time=2015-07-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29742, encodeId=cb6e29e4212, content=,, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:53:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29741, encodeId=350529e417b, content=。, beContent=null, objectType=article, channel=null, level=null, likeNumber=175, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:53:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29740, encodeId=3d5e29e402d, content=,, beContent=null, objectType=article, channel=null, level=null, likeNumber=130, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:53:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29739, encodeId=90d729e3974, content=,, beContent=null, objectType=article, channel=null, level=null, likeNumber=130, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:53:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29738, encodeId=07ae29e3858, content=。, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:52:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29737, encodeId=1b9129e3741, content=!, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:52:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29680, encodeId=bb1b296804c, content=(⊙o⊙), beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12a31627589, createdName=18619c0a62m, createdTime=Sat Jun 27 09:23:00 CST 2015, time=2015-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29681, encodeId=19f22968147, content=O__O"…, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12a31627589, createdName=18619c0a62m, createdTime=Sat Jun 27 09:23:00 CST 2015, time=2015-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29679, encodeId=8689296e971, content=呵呵(^_^), beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12a31627589, createdName=18619c0a62m, createdTime=Sat Jun 27 09:23:00 CST 2015, time=2015-06-27, status=1, ipAttribution=)]
    2015-06-27 18619c0a62m

    O__O"…

    0

  10. [GetPortalCommentsPageByObjectIdResponse(id=31807, encodeId=ce8f3180e07, content=长见识了, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=01621631568, createdName=飞翔9899, createdTime=Thu Jul 09 11:34:00 CST 2015, time=2015-07-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29742, encodeId=cb6e29e4212, content=,, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:53:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29741, encodeId=350529e417b, content=。, beContent=null, objectType=article, channel=null, level=null, likeNumber=175, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:53:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29740, encodeId=3d5e29e402d, content=,, beContent=null, objectType=article, channel=null, level=null, likeNumber=130, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:53:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29739, encodeId=90d729e3974, content=,, beContent=null, objectType=article, channel=null, level=null, likeNumber=130, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:53:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29738, encodeId=07ae29e3858, content=。, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:52:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29737, encodeId=1b9129e3741, content=!, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150526/IMG5564536F3C41D5237.jpg, createdBy=4c0c1612254, createdName=summer474cn, createdTime=Sun Jun 28 06:52:00 CST 2015, time=2015-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29680, encodeId=bb1b296804c, content=(⊙o⊙), beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12a31627589, createdName=18619c0a62m, createdTime=Sat Jun 27 09:23:00 CST 2015, time=2015-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29681, encodeId=19f22968147, content=O__O"…, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12a31627589, createdName=18619c0a62m, createdTime=Sat Jun 27 09:23:00 CST 2015, time=2015-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29679, encodeId=8689296e971, content=呵呵(^_^), beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12a31627589, createdName=18619c0a62m, createdTime=Sat Jun 27 09:23:00 CST 2015, time=2015-06-27, status=1, ipAttribution=)]
    2015-06-27 18619c0a62m

    呵呵(^_^)

    0

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