CN103381170B - Chukrasone A在制备抗血小板聚集药物中的应用 - Google Patents
Chukrasone A在制备抗血小板聚集药物中的应用 Download PDFInfo
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Abstract
本发明涉及<b>Chukrasone？A</b>在制备抗血小板聚集药物中的应用。本发明涉及的<b>Chukrasone？A</b>在制备抗血小板聚集药物中的用途属于首次公开，由于骨架类型属于全新的骨架类型，而且其抗血小板聚集活性强得意想不到，不存在由其他化合物给出任何启示的可能，具备突出的实质性特点，同时用于抗血小板聚集显然具有显著的进步。
Description
技术领域
本发明涉及ChukrasoneA的新用途，更具体地说涉及该化合物在制备抗血小板聚集药物中的应用。
背景技术
血小板的基本生理功能是黏附、聚集、释放和分泌颗粒内容物(如ATP、5-羟色胺)，静息状态的血小板转变为生理功能状态即为血小板的活化。血小板活化后能提供磷脂表面，促进血液凝固的进行，形成由纤维蛋白包绕血小板组成的血栓。因此血小板作为血液的一种有形成分，在生理的止血和病理的血栓形成过程中，扮演了非常重要的角色。临床研究表明，临床上常见的心脑血管疾病如高血压、心绞痛心肌梗塞、脑梗塞及脑出血等基本，均与血小板功能变化和血液流变学异常有关。目前常用的抗血小板药都有较重的不良反应，因此开发研制新型有效、不良反应小的治疗与预防血小板聚集的药物已经刻不容缓。本发明人通过实验研究，发现ChukrasoneA具有抗血小板聚集的作用。
本发明涉及的化合物ChukrasoneA是一个2012年发表(Liu,H.B.etal.,2012.ChukrasonesAandB:PotentialKv1.2PotassiumChannelBlockerswithNewSkeletonsfromChukrasiatabularis.OrganicLetters14(17),4438–4441.)的新骨架化合物，该化合物拥有全新的骨架类型，目前的用途仅仅涉及钾离子通道抑制活性(Liu,H.B.etal.,2012.ChukrasonesAandB:PotentialKv1.2PotassiumChannelBlockerswithNewSkeletonsfromChukrasiatabularis.OrganicLetters14(17),4438–4441.)，对于本发明涉及的ChukrasoneA在制备抗血小板聚集药物中的用途属于首次公开，由于骨架类型属于全新的骨架类型，而且其抗血小板聚集活性强得意想不到，不存在由其他化合物给出任何启示的可能，具备突出的实质性特点，同时用于抗血小板聚集显然具有显著的进步。
发明内容
本发明提供了ChukrasoneA在制备抗血小板聚集药物中的应用。
本发明以阿司匹林和氯吡格雷作为阳性药，通过实验证明，ChukrasoneA能明显的抑制血小板聚集指数均显著降低，与阳性药持平。
所述化合物ChukrasoneA结构如式(Ⅰ)所示：
本发明涉及的ChukrasoneA在制备抗血小板聚集药物中的用途属于首次公开，由于骨架类型属于全新的骨架类型，而且其抗血小板聚集活性强得意想不到，不存在由其他化合物给出任何启示的可能，具备突出的实质性特点，同时用于抗血小板聚集显然具有显著的进步。
具体实施方式
本发明所涉及化合物ChukrasoneA的制备方法参见文献(Liu,H.B.etal.,2012.ChukrasonesAandB:PotentialKv1.2PotassiumChannelBlockerswithNewSkeletonsfromChukrasiatabularis.OrganicLetters14(17),4438–4441.)。
以下通过实施例对本发明作进一步详细的说明，但本发明的保护范围不受具体实施例的任何限制，而是由权利要求加以限定。
实施例1：本发明所涉及化合物ChukrasoneA片剂的制备：
取20克化合物ChukrasoneA，加入制备片剂的常规辅料180克，混匀，常规压片机制成1000片。
实施例2：本发明所涉及化合物ChukrasoneA胶囊剂的制备：
取20克化合物ChukrasoneA，加入制备胶囊剂的常规辅料如淀粉180克，混匀，装胶囊制成1000片。
下面通过药效学实验来进一步说明其药物活性。
试验例1：ChukrasoneA对大鼠血小板聚集功能的影响
1.动物：清洁级Sprague-Dawley大鼠，雄性，体重200g—250g。
2.方法与结果
动物随机分为空白对照组(等容量溶剂)、阿司匹林组(ASA，50mg/kg)、氯吡格雷组(7mg/kg)、ChukrasoneA0.625mg/kg组、ChukrasoneA1.25mg/kg组、ChukrasoneA2.5mg/kg组，每组8只，灌胃给药，1次/d，连续5d。于末次给药后1h，以3％戊巴比妥钠分别麻醉大鼠(30mg/kg)，经腹主动脉采血，以3.8％枸橼酸钠溶液抗凝(血：抗凝剂＝9:1)，1000r/min，分离富血小板血浆(PRP)，剩余部分再以3000r/min离心15min，分离贫血小板血浆(PPP)，按比浊法以ADP(252umol/L)为诱导剂，用LBY-NJ血液凝聚仪测定5min内血小板聚集率，并按以下公式计算血小板聚集抑制率，数据用表示，以组间t检验进行统计学处理，结果见表1。
根据实验结果可知，ChukrasoneA各剂量组可明显抑制体内血小板聚集，药效与阳性药阿司匹林和氯吡格雷持平。
表1ChukrasoneA对血小板的聚集抑制率(n＝8)
与空白对照组比较：**p<0.01
结论：以阿司匹林和氯吡格雷作为阳性药，通过实验证明，ChukrasoneA能明显的抑制血小板聚集，与阳性药持平,可以用来制备抗血小板聚集药物。
Claims (1)
1.ChukrasoneA在制备抗血小板聚集药物中的应用，所述化合物ChukrasoneA结构如式（Ⅰ）所示：
式（Ⅰ）。
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Non-Patent Citations (1)
| Title |
|---|
| Chukrasones A and B: Potential Kv1.2 Potassium Channel Blockers with New Skeletons from Chukrasia tabularis;Hong-Bing Liu et. al.;《Organic Letters》;20120810;第14卷(第17期);第4438–4441页 * |
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