阿司匹林，史上第一个明星药物，享誉盛名却低调到尘埃里

发布时间： 2017-11-20

 阿司匹林(乙酰水杨酸)，一颗冉冉上升的新星，带着性感的光芒，亮瞎了无数人的双眼。下一个叫做阿什么林(阿莫西林)的也引爆了第二代药物革命，成为了抗细菌药物的中流砥柱。

一

十八世纪，人们对于流感依旧非常困恼。东方人拿着砂锅没日没夜熬着味道呛人的中药，捏着鼻子喊着良药苦口咬牙一饮而尽，西方人拿着小刀在血管上切上一个小口子，说流血不流泪，信奉所有的疾病都可以用放血来解决。

 

大家翘首以盼，期待着一个药物横空出世，带给大家一点点惊喜，情不自禁。

 

在这个大众创业，万众创新的时代，一个小作坊的年轻人信誓旦旦对着大家说我来吧，本来做染坊生意的小作坊也凭借他一跃成为了国际药企百年老字号 - 拜耳。

 

1898年8月1日他没有辜负大家的期望，成功上市。之后的日子，无数的鲜花和掌声纷至沓来，他成为了史上第一个明星药物；史上最畅销的药物，顺便打破了吉尼斯世界纪录；史上最经典的三个药物之首；和二甲双胍一切扛起了神药的大旗……

 

他就是阿司匹林(乙酰水杨酸)，一颗冉冉上升的新星，带着性感的光芒，亮瞎了无数人的双眼。下一个叫做阿什么林(阿莫西林)的也引爆了第二代药物革命，成为了抗细菌药物的中流砥柱。

二

 

阿司匹林不同于现在的西药，没有动辄五六百的分子量，没有花里花哨的结构。

 

他强任他强，一苯一羧一酯基。

他横由他横，分子只要一八零。

 

他崇尚着重剑无锋，大巧不工的原则，不滞于物，草木碎石皆可成剑。简单直接震撼着你的心灵。浓缩就是精华，把空间发挥到了极致。

 

他志在千里，却低调像尘埃，简单的结构，屌丝的身世，不像青蒿素、吗啡、紫杉醇来自于名门望族，他只是从杨树皮里面演化而来。

 

三

 

古今中外，早有柳叶柳树皮煎煮治疗疼痛的记载。后来化学家从里面分离提纯到了其中的关键成分 - 水杨酸，而阿司匹林仅仅是在水杨酸上加入了一个乙酰基，正是由于这个点睛之笔让阿司匹林成为史上最神奇的神药。

 

水杨酸在治疗疼痛、发烧和炎性疾病中确实疗效确切，可是让人难以接受的味道、对胃强烈的刺激……也难让他成为一个好的药物。

 

经过简单的乙酰基修饰水杨酸的酚羟基，让如此不讨好的化合物摇身一变成为了炙手可热的明星药物。

 

良好的疗效，解决了之前对胃强烈的刺激。他成为了那时候的网红，从东到西，从南到北，刷爆了别人的朋友圈。

 

今日药条发布消息，一个神奇的小子，华尔街为之疯狂的药物。

 

央视网独家专访，阿司匹林何以引起现象级的轰动？

 

躺在藤椅上听着地中海此起彼伏的浪涛声和微风交织的交响曲，刷着朋友圈，风光无限。

四

不过后续的临床试验不断报道出，阿司匹林容易导致出血，也会引起胃肠道不适的问题。

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1971年，发表在自然杂志的三篇论文揭示了阿司匹林的作用机制。文中指出阿司匹林通过抑制环氧化酶(COX)，减少了前列腺素的产生。而前列腺素在人体内可以发挥很多的作用，如炎症信号的传导、痛感的传递以及体温的控制。因此前列腺素被阿司匹林抑制后，就具有了止痛、消炎和退烧的作用。

 

COX包括2种同工酶异构体，即COX-1和COX-2。COX-1是一种固有的看家酶，它主要存在于胃、肾脏和血小板中，催化产生生理需要的前列腺素E(PGE)，调节外周血管阻力，维持肾血流量，保护胃黏膜及调节血小板聚集。

 

而长时间大剂量服用阿司匹林后，也会因为抑制胃肠道膜上的COX-1，减少了前列腺素生成，使胃肠道黏膜失去了前列腺素的保护。

 

而此时，为了解决阿司匹林酸性对于胃肠道的刺激和胃出血的现象，对乙酰氨基酚、布洛芬等新非甾体抗炎药和选择性COX-2抑制剂相继被开发，这也导致阿司匹林后市场上的节节败退。

五

打开网易云音乐，放起了平凡之路。歌声断断续续拍打着他的耳膜，“我曾经跨过山河大海， 也穿过人山人海，我曾经拥有着的一切， 转眼都飘散如烟”。

 

坐在人潮涌动的街头一角，喝着泛着泡沫的啤酒，曾经撸串的小伙伴一个个离他而去。往事历历在目，想着当年金戈铁马意气风发的日子，风起云涌，不禁潸然泪下。

 

可是时间像场闹剧秀，时不时给你挑逗下开个玩笑，那一夜有更多的小鲜肉出道而他却颜值不再。他失去了往日市场的号召力，不知何时会被人们所忘记。

 

经过了几年的低潮，他变得更加睿智祥和，不再为一城一池而斤斤计较，这一次他将卷土重来，老骥伏枥志在千里，姜还是老的辣，这一次的他更加光芒万丈，让那些后辈都汗颜。

 

阿司匹林抑制COX酶，也会抑制凝血素A2，具有抗血栓的作用。曾经的胃溃疡出血也是因为这个缘由而更加严重。

 

汝之蜜糖，彼之砒霜。没有绝对的副作用，只有放错位置的药物。后来的日子里沙利度胺和西地那非也是听取了这个而东山再起的。

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background-color: rgb(238, 237, 235); background-size: 22px; background-position: 50% 50%; background-repeat: no-repeat; display: inline;" _src="http://www.xinyaohui.com/file/upload/201711/19/213904742002.jpg">

 

六

 

阿司匹林在人体一部分水解成水杨酸，具有消炎的作用，一部分可以以乙酰水杨酸分子形式存在，后者可以对环氧化酶进行乙酰化，具有其他抗炎药不具备的活性作用，包括血小板活性、抗肿瘤活性……

 

大剂量服用消炎、中剂量镇痛、小剂量防止血小板凝集引起的血栓，降低心血管发病率和死亡率，长期服用可以缓解阿尔兹海默症、大肠癌病情发展……

 

那一刻，他重回江湖的巅峰，成为了一个万能神药，长期服用可以预防多种疾病。

 

看着朋友圈又一次的追捧，起起落落，曾经的风度翩翩，今天的大隐隐于市，这一刻他却分外安详，只想淡出人们的视野，低调开发更多的适应症来服务大众，把聚光灯留给那些春风得意的新人们。

 

那片让他饱受挫折的领域，他依旧不离不弃，通过改良剂型，又杀了回马枪回来，成为了其中的中坚力量。

 

为了减少对于胃部的刺激，开发了肠溶片；为了方便小孩子服用，做出了阿司匹林的沸腾片；方便临时服用，弄出了阿司匹林的咀嚼片；为了减轻副作用，降低剂量，做出了鼻剂、缓释剂……

 

根据不同的临床用途，他日夜操劳做出不同的剂型，简单直接却震撼了你的心灵。

七

 

每年生产的一千多亿片阿司匹林，连起来可以绕地球好几圈；每年阿司匹林挽救有几十万患者生命，免于心肌梗塞、脑卒中；失去了专利保护的情况下，依旧还有十亿美元左右的销售额。

 

如今，阿司匹林已经成为了领域的模范教材，无数的后辈都看着他熠熠生辉的背影而钦佩不已。

 

做成前药减轻副作用、老药新用开发更多的适应症、开发不同的剂型这已经成为了行业开疆扩土的经验了。

 

江山代有才人出，各领风骚出百年。属于他的时代已经不复返，竭尽全力只是为了追赶之前的步伐，一个低调的老者，百年老药，重剑无锋大巧无工。

 

参考文献：

[1] Group A D C. Aspirin in Alzheimer's disease(AD2000): a randomised open-label trial[J]. The Lancet Neurology, 2008, 7(1):41-49

[2] Vane J R. Inhibition of prostaglandinsynthesis as a mechanism of action for aspirin-like drugs[J]. Nature, 1971, 231(25):232-235.

[3] 新药研发案例研究，白东鲁，沈竞康主编

 

[4] Drew D A, Cao Y, Chan A T. Aspirin andcolorectal cancer: the promise of precision chemoprevention[J]. Nature ReviewsCancer, 2016, 16(3): 173-186.

 

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