CN103393698B - Chukrasone A在制备治疗或预防慢性心衰的药物中的应用 - Google Patents
Chukrasone A在制备治疗或预防慢性心衰的药物中的应用 Download PDFInfo
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Abstract
本发明提供了Chukrasone A在制备治疗或预防慢性心衰的药物中的应用，具体地提出了Chukrasone A对急、慢性心力衰竭的治疗作用。本发明涉及的Chukrasone A在制备治疗慢性心衰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，而且其治疗慢性心衰的活性强得意想不到，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，同时用于治疗慢性心衰显然具有显著的进步。
Description
发明领域
本发明涉及Chukrasone A在制备治疗或预防慢性心衰的药物中的应用。
背景技术
心衰(hear failure，HF)是指心脏功能异常导致心脏泵血量不能满足组织代谢需要的一种病理生理状态。病因诱因因为心脏负荷过重、心肌本身、舒张受限任何原因致初始心肌损伤引起结构功能低下而进行性发病；而感染、贫血、妊娠、分娩、心律紊乱、肺栓塞、甲亢、糖尿病、抑制心脏药诱发加重HF。发病机理过去认为HF发生发展的机制是血流动力学异常；20世纪80年代后期认识到神经-内分泌激素的激活起重要作用(交感↑NE↑RAS↑等激活)；90年代以后逐渐明确了“心肌重塑”(remodelling)是导致心衰的发生发展的基本机制。
本发明涉及的化合物Chukrasone A是一个2012年发表(Liu,H.B.et al.,2012.Chukrasones A and B:Potential Kv1.2Potassium Channel Blockers withNew Skeletons from Chukrasia tabularis.Organic Letters 14(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.et al.,2012.Chukrasones A and B:Potential Kv1.2Potassium Channel Blockers with New Skeletons fromChukrasia tabularis.Organic Letters 14(17),4438–4441.)，对于本发明涉及的Chukrasone A在制备治疗慢性心衰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，而且其治疗慢性心衰的活性强得意想不到，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，同时用于治疗慢性心衰显然具有显著的进步。
发明内容
本发明提供了Chukrasone A在制备治疗或预防慢性心衰的药物中的应用。
所述化合物Chukrasone A结构如式(Ⅰ)所示：
本发明涉及的Chukrasone A在制备治疗慢性心衰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，而且其治疗慢性心衰的活性强得意想不到，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，同时用于治疗慢性心衰显然具有显著的进步。
具体实施方式
本发明所涉及化合物Chukrasone A的制备方法参见文献(Liu,H.B.et al.,2012.Chukrasones A and B:Potential Kv1.2Potassium Channel Blockers with NewSkeletons from Chukrasia tabularis.Organic Letters 14(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Chukrasone A片剂的制备：
取20克化合物Chukrasone 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Chukrasone A胶囊剂的制备：
取20克化合物Chukrasone 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。
实验例Chukrasone A对慢性心衰大鼠的影响
试验方法与结果
大鼠100只，雌雄各半，取100只腹腔注射盐酸阿霉素2mg/kg，每周1次，共6周。随机分为10组，即NS组，卡托普利片12.5mg/kg组，灌胃给药ChukrasoneA 0.2mg/kg组，灌胃给药Chukrasone A 2.5mg/kg组，灌胃给药Chukrasone A5.0mg/kg组。第5周起每日给予Chukrasone A灌胃各组，给药21天。20％乌拉坦1.1g/kg腹腔注射麻醉，手术剥离气管并插管，同时游离出右侧总动脉，经其插入自制的心室插管(直径1mm，充满1％肝素)，描记血压曲线；再继续插入，使其通过左侧动脉瓣进入左心室，描记室内压曲线，自动分析处理左室收缩压(LVSP)，心室内压最大上升速率(+dp/dtmax)，心室内压最大下降速度(-dp/dtmax)和实测心肌最大收缩速度(Vpm)等数据。另取10只大鼠作为正常对照组，不给予盐酸阿霉素，其余操作同上述，组间T检验，进行统计学处理。
表1 Chukrasone A对慢性心衰大鼠心功能的影响(n＝10)
与NS组比较，△：p<0.05，△△：p<0.01
表1试验结果表明Chukrasone A灌胃给药0.2mg/kg组能升高由盐酸阿霉素导致的心衰大鼠的LVSP，+dp/dtmax，-dp/dtmax和Vpm的降低(与NS组比较，P<0.05)；Chukrasone A灌胃给药2.5mg/kg、5.0mg/kg能显著升高由盐酸阿霉素导致的心衰大鼠的LVSP，+dp/dtmax，-dp/dtmax和Vpm的降低(与NS组比较，P<0.01)。
结论：Chukrasone A具有显著的治疗或预防慢性心衰的作用，可以用来制备治疗或预防慢性心衰的药物。
Claims (1)
1.Chukrasone A在制备治疗或预防慢性心衰的药物中的应用，所述化合物Chukrasone A结构如式（Ⅰ）所示：
式（Ⅰ）。
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| CN201310278625.XA CN103393698B (zh) | 2013-07-04 | 2013-07-04 | Chukrasone A在制备治疗或预防慢性心衰的药物中的应用 |
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Non-Patent Citations (2)
| Title |
|---|
| Liu,H.B.et al.Chukrasone A and B:Potential Kv1.2 Potassium Channel Blockers with New Skeletons from Chukrasia tabularis.《Organic Letters》.2012,第14卷(第17期),第4438–4441页. * |
| 王冬艳,等.钾离子通道作为肿瘤治疗靶点的研究.《国外医学药学分册》.2006,第33卷(第4期),第246-248,265页. * |
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