CN102872035B - Gypensapogenin A在制备抗血小板聚集药物中的应用 - Google Patents
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Abstract
本发明涉及GypensapogeninA在制备抗血小板聚集药物中的应用。本发明涉及的GypensapogeninA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Gypensapogenin A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Gypensapogenin A具有抗血小板聚集的作用。
本发明涉及的化合物Gypensapogenin A是一个2012年发表（Li, N. et al., 2012. Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. European Journal of Medicinal Chemistry 50, 173–178.）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人肿瘤细胞株的细胞毒活性（Li, N. et al., 2012. Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. European Journal of Medicinal Chemistry 50, 173–178.），对于本发明涉及的Gypensapogenin A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Gypensapogenin A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，Gypensapogenin A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Gypensapogenin A结构如式（Ⅰ）所示：
式（Ⅰ）
本发明涉及的Gypensapogenin A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Gypensapogenin A的制备方法参见文献（Li, N. et al., 2012. Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. European Journal of Medicinal Chemistry 50, 173–178.和Wei, J.X. et al., 1982. Two new dammaran sapogenins from leaves of Panax notoginseng. Planta Medica, 45(3): 167-171.）。
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Gypensapogenin A片剂的制备：
取20克化合物Gypensapogenin A，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Gypensapogenin A胶囊剂的制备：
取20克化合物Gypensapogenin A，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：Gypensapogenin A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，50 mg/kg）、氯吡格雷组（7 mg/kg）、Gypensapogenin A 0.625 mg/kg组、Gypensapogenin A 1.25 mg/kg组、Gypensapogenin A 2.5 mg/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（30 mg/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），1000 r/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，Gypensapogenin A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1 Gypensapogenin A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，Gypensapogenin A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.Gypensapogenin A在制备抗血小板聚集药物中的应用，所述化合物Gypensapogenin A结构如式（Ⅰ）所示：
式（Ⅰ）。
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