CN102861034B - Gypensapogenin A在治疗或预防急性心衰的药物中的应用 - Google Patents
Gypensapogenin A在治疗或预防急性心衰的药物中的应用 Download PDFInfo
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Abstract
本发明提供了Gypensapogenin A在制备治疗或预防心衰的药物中的应用。本发明涉及的Gypensapogenin A在制备治疗急性心衰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，而且其治疗急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，同时用于治疗急性心衰显然具有显著的进步。
Description
发明领域
本发明涉及Gypensapogenin A在制备治疗或预防急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在制备治疗急性心衰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，而且其治疗急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，同时用于治疗急性心衰显然具有显著的进步。
发明内容
本发明提供了Gypensapogenin A在制备治疗或预防急性心衰的药物中的应用。
所述化合物Gypensapogenin A结构如式（Ⅰ）所示：
式（Ⅰ）
本发明涉及的Gypensapogenin A在制备治疗急性心衰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，而且其治疗急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，同时用于治疗急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 ofPanax 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：Gypensapogenin A对犬急性心力衰竭的治疗作用
1 材料动物健康成年犬体重12.5~13.5 kg。戊巴比妥钠（Sigma，进口分装，规格：25g）；仪器美国BIC16导生理记录仪（美国BIC公司生产）；电磁流量计（MFV-3200型）：日本光电公司生产。
2 试验方法与结果
将犬随机分为NS组（等容量溶剂），灌胃给药Gypensapogenin A 2.0 mg/kg组、1.0 mg/kg组、0.2 mg/kg组，每组6只。禁食12小时后，静脉注射戊巴比妥钠40 mg/kg麻醉，气管插管，人工呼吸，监测主动脉压（AP）与心电图。左侧开胸，从心尖插导管至左室压及其压力变化速度（±dp/dtmax）。将Waltan-Brodie应变弓植入左心室前壁，测定心肌收缩力。用电磁流量计测定升主动脉血流量。以升主动脉流量作为心输出量（CO），计算心脏指数（CI），每搏指数（SI），每搏作功（SW），左心作功（LVW）。各项参数记录与BIC生理记录仪。术后半小时，各项参数达到稳定。从股静脉恒速输注戊巴比妥钠（0.5 mL/kg·min），以±dp/dtmax下降到约1000 mHg/s为主要指标形成急性心力衰竭。待急性心衰模型稳定后，各组动物十二指肠给予相应药物。组间T检验，进行统计学处理。
表1 Gypensapogenin A对心力衰竭犬dp/dt的影响（n=6，X±s）
与NS组比较，p<0.05，p<0.01
表2 Gypensapogenin A对心力衰竭犬心脏作功的影响（n=6，X±s）
与给药前比较*p<0.05，**p<0.01；与NS组比较p<0.05，p<0.01
结果如表1、2所示，滴注不同剂量Gypensapogenin A可增加心衰犬的SW、LVW、+dp/dt（与模型组对照组比较，p<0.05or p<0.01）。灌胃不同剂量Gypensapogenin A可增加心衰犬的SW、LVW、+dp/dt（与模型组对照组比较，p<0.01or p<0.05）。
表3 Gypensapogenin A对心力衰竭犬心输出量的影响（n=6，X±s）
与给药前比较*p<0.05，**p<0.01；与NS组比较p<0.05，p<0.01
结果如表3所示，滴注不同剂量Gypensapogenin A可增加心衰犬的心输出量（与模型对照组比较，p<0.01or p<0.05）。灌胃不同剂量Gypensapogenin A可增加心衰犬的心输出量（与模型对照组比较，p<0.01or p<0.05）。
结论：Gypensapogenin A能够显著改善急性心衰，可以用来制备治疗或预防心衰的药物。
Claims (1)
1.Gypensapogenin A在制备治疗或预防急性心衰的药物中的应用，所述化合物Gypensapogenin A结构如式（Ⅰ）所示：
式（Ⅰ）。
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