CN112641095A - 含有槭叶蚊子草提取物的食品组合物和药物组合物 - Google Patents
含有槭叶蚊子草提取物的食品组合物和药物组合物 Download PDFInfo
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Abstract
本发明公开了一种槭叶蚊子草醇提取物和从其中分离出的溶剂提取部位,或从槭叶蚊子草的乙酸乙酯提取部位中完全分离出的新化合物1和2,它们具有对HMG‑CoA还原酶活性的优异抑制作用,优异的抗氧化作用以及在巨噬细胞中抑制泡沫细胞形成的优异作用。另外,本发明还公开了用于治疗、预防和改善由高胆固醇血症引起的血管疾病,高胆固醇血症或心脏病或用于降低胆固醇水平的药物组合物或保健食品组合物,其含有作为活性成分的槭叶蚊子草醇提取物和溶剂提取部位或新化合物1和2。
Description
相关申请的交叉引用
本申请根据35 U.S.C.§119(a)要求于2019年10月10日提交的韩国专利申请第10-2019-0125191号的优先权,其全部内容通过引用合并于此。
技术领域
本发明涉及一种用于制备用于降低血胆固醇水平和改善动脉粥样硬化的含有槭叶蚊子草提取物的食品组合物和治疗性药物组合物的方法。
背景技术
胆固醇存在于人的每个部分,包括脑,神经,肌肉,皮肤,肝脏,肠,心脏等,并且作为体内细胞膜的成分是参与各种生化反应的必需物质。然而,过多的胆固醇可能会积聚在血管内皮细胞或内皮中,导致血管疾病(例如高脂血症),从而导致继发性疾病(例如动脉硬化,高血压,肥胖症和糖尿病)。3-羟基-3-甲基戊二酰辅酶A还原酶(以下称为“HMG-CoA还原酶”)是介导甲羟戊酸合成的酶,甲羟戊酸是甾醇或类异戊二烯化合物生物合成途径中的中间体。当降低HMG-CoA还原酶的活性时,可以通过抑制胆固醇的生物合成获得降低血液中脂质和胆固醇水平的效果。高脂血症,尤其是高胆固醇血症,由于脂质在包括冠状动脉,颈动脉和外周动脉的动脉中异常分布的脂质沉积而导致动脉血栓形成,从而造成动脉硬化,其中脂质沿血管厚积聚,其减少血液流量,从而导致缺血性心脏病和/或心血管障碍或疾病,如心绞痛和心肌梗塞。于是,由于高脂血症和动脉硬化彼此密切相关,所以HMG-CoA还原酶抑制剂可以通过治疗高脂血症来预防动脉硬化。非专利文献1公开了,HMG-CoA还原酶抑制剂用于治疗高脂血症,由于其降低总胆固醇和LDL(低密度脂蛋白)-胆固醇水平的作用。非专利文献2至4公开了,HMG-CoA还原酶抑制剂用于预防和治疗动脉粥样硬化。非专利文献5至7公开了,HMG-CoA还原酶抑制剂用于预防和治疗与心血管系统有关的障碍或疾病。非专利文献8至12公开了,HMG-CoA还原酶抑制剂用于预防和治疗动脉粥样硬化。
同时,非专利文献13至14公开了已知活性氧(ROS)会产生过氧化物和自由基等,因此导致包括蛋白质,脂肪,DNA和RNA在内的细胞损伤,并涉及诸如动脉硬化,帕金森氏病和阿尔茨海默氏病等疾病,由于LDL的氧化和脂质过氧化作用。根据非专利文献15至17,已知氧化的LDL被引入巨噬细胞,内皮细胞和平滑肌细胞中,引起动脉粥样硬化,并且在动脉粥样硬化的阶段,由于引入了氧化的LDL,巨噬细胞形成泡沫细胞,从而导致动脉粥样硬化斑块。动脉粥样硬化是一种系统性血管疾病,是血栓性脑梗塞的最常见原因,也是心肌梗塞,周围血管梗阻以及脑梗塞的最常见原因。目前,已经开发出许多药物作为HMG-CoA还原酶抑制剂,并且其中代表性的是使用广泛的他汀类药物。他汀类药物的具体例子包括洛伐他汀,辛伐他汀,瑞舒伐他汀,普伐他汀,氟伐他汀,美伐他汀,阿托伐他汀,西立伐他汀等。然而,他汀类药物已知会在中枢神经系统中造成副作用等。
因此,迫切需要开发出无副作用的新型HMG-CoA还原酶抑制剂,或能够抑制泡沫细胞形成的动脉粥样硬化性血管疾病的新型治疗和预防试剂。近来,人们越来越关注天然药物以克服合成药物的缺点(抗性,副作用等)或替代合成药物。
在背景技术部分中公开的上述信息仅用于增强对本发明背景技术的理解,因此,其可能包含不构成该国本领域普通技术人员已知的现有技术的信息。
[现有技术文献]
[专利文献]
(专利文献1)韩国专利公开No.10-2014-0045134出版文本,标题为“用于预防或治疗肥胖症或代谢性疾病的药物组合物,其包含胡麻菜(Aster glehni)的提取物或其提取部位作为活性成分”
(专利文献2)韩国专利公开No.10-2018-0113013出版文本,标题为“用于预防和治疗动脉硬化的药物组合物,其包含绳状龙须菜(Gracilariopsis chorda)的提取物或其提取部位作为活性成分”
(专利文献3)韩国专利公开No.10-2016-0084990出版文本,标题为“包含刺槐(Robinia pseudoacacia)的用于治疗动脉硬化的组合物”
(专利文献4)韩国专利公开No.10-2016-001805出版文本,标题为“包含发酵的人参(Panax ginseng)提取物的抗高脂血症和抗动脉粥样硬化组合物”
(专利文献5)韩国专利登记No.10-1516764,标题为“一种用于预防或治疗动脉硬化的组合物,其中含有葎草(Humulus japonicus)提取物”
[非专利文献]
(非专利文献1)Grundy S.M.,N.Engl.J.Med.,319(1):24-33,1988
(非专利文献2)Mantell G.,Clin.Exper.Hyper.A部分,理论与实践,11(5-6),927-41,1989
(非专利文献3)Hamaoka A.等人,J.Cardiol.56(2),245―253,2010
(非专利文献4)Liu B.等人,Int.Med.(东京,日本)51(10),1177-1182,2012
(非专利文献5)Kolyada A.Y.等人,高血压,38(5),1024-1029,2001
(非专利文献6)Martinez-Gonzalez J.等人,动脉粥样硬化159,27-33,2001
(非专利文献7)Ito H.等人,J.Atheroscler.血栓.8(2),33-44,2001
(非专利文献8)Lutgens E.和Daemen Mat J.A.P.,今日药物发现:治疗策略1(2),189-194,2004
(非专利文献9)AL-Otaibi D.D.,和Novotny L.,Res.J.Pharm.Biol.Chem.Sci.,6(1),449-460,2015
(非专利文献10)Kishida Y.等人,J.Pharm.Soc.日本,111(9),469-487,1991
(非专利文献11)Tikkanen M.J等人,Euro.Heart J.,8Suppl.E,97-101,1987
(非专利文献12)Jung H.A.等人,Arch.Pharm.Res.,22,213-218,1999
(非专利文献13)Miyake Y.等人,J.Agric.Food Chem.,48,3217-3224,2000
(非专利文献14)Witztum J.L.,S.D.,J.Clin.Invest.,88,1785-1792,1991
(非专利文献15)Ylaherttuala S.等人,J.Clin.Invest.,84,1086-1095,1989
(非专利文献16)Galle J.等人,动脉粥样硬化185,219-226,2006。
发明内容
为了解决与现有技术有关的上述问题而完成了本发明,并且,在研究天然原料的药物活性时,本发明人发现槭叶蚊子草的醇提取物,从其中分离出的溶剂提取部位,以及新化合物1和2表现出抑制HMG-CoA还原酶活性和抑制泡沫细胞形成的优异效果,所述泡沫细胞是由于在巨噬细胞中引入了氧化的LDL而形成的,并且还表现出优异的抗氧化作用。基于该发现,完成了本发明。
因此,本发明的一个目的是提供一种具有针对HMG-CoA还原酶活性的抑制作用,抗氧化作用和抑制泡沫细胞形成的作用的药物组合物,以治疗、改善和预防高胆固醇血症或高胆固醇血症引起的心脏病或血管疾病,所述药物组合物含有作为活性成分的槭叶蚊子草的醇提取物或其提取部位以及新化合物1和2。
本发明的另一个目的是提供一种具有针对HMG-CoA还原酶活性的抑制作用,抗氧化作用和抑制泡沫细胞形成的作用保健食品组合物,以治疗、改善和预防高胆固醇血症或高胆固醇血症引起的心脏病或血管疾病,所述药物组合物含有作为活性成分的槭叶蚊子草的醇提取物或其提取部位以及新化合物1和2。
本发明的另一个目的是提供一种用于制备槭叶蚊子草的醇提取物或从其中分离出的溶剂提取部位的方法,以及一种通过使用柱层析法等通过一系列分离步骤从其中分离出的乙酸乙酯提取部位中制备新化合物1和2的方法,所述新化合物1和2对HMG-CoA还原酶活性具有优异的抑制作用。
本发明的另一个目的是提供一种具有抗氧化作用的药物组合物,用于治疗和预防心脏病或血管疾病,所述药物组合物含有作为活性成分的槭叶蚊子草的醇提取物或从其中分离出的溶剂提取部位。
本发明的目的不限于上述那些目的。从以下描述中将清楚地理解本发明的目的,并且本发明的目的可以通过权利要求中限定的手段及其组合来实现。
为了实现上述目的,本发明提供以下组合物或化合物:
一方面,本发明提供了一种组合物,其包含作为活性成分的槭叶蚊子草的醇提取物或其提取部位和由以下式1或2表示的新的化合物:
[式1]
[式2]
所述组合物可以是用于治疗、改善和预防高胆固醇血症或由高胆固醇血症引起的心脏病或血管疾病的药物组合物或保健食品组合物。
在另一方面,本发明提供了一种从槭叶蚊子草的溶剂提取物中分离具有优异的降低血胆固醇水平和改善高脂血症活性的活性化合物或该提取物的乙酸乙酯提取部位的方法,所述方法包括以下步骤:
(步骤1)第一步,通过制备槭叶蚊子草的C1-C5醇类提取物并用二氯甲烷,乙酸乙酯或丁醇分离该提取物以获得溶剂提取部位;和
(步骤2)第二步,使用硅胶,Sephadex LH-20,Toyopearl HW-40,反相硅胶,HPLC等通过一系列分离步骤,使用C1-C5醇类和第一步中获得的乙酸乙酯提取部位中的有机溶剂,获得新化合物1和2。
在另一方面,本发明提供了一种组合物,其包含作为活性成分的,在上述第一步和第二步中获得的槭叶蚊子草的醇提取物和从其中分离出的溶剂提取部位,或从其中分离出的槭叶蚊子草的乙酸乙酯提取部位中完全分离出的式1或2表示的新化合物。
所述组合物可以是药物组合物或保健食品组合物,用于治疗和预防高胆固醇血症或由高胆固醇血症引起的心脏病或血管疾病。
下文讨论本发明的其他方面和优选实施例。
附图说明
现在将参考本发明的某些示例性实施例详细描述本发明的上述和其他特征,这些示例性实施例在附图中示出,在下文中仅以举例说明的方式给出,因而并不限制本发明,并且其中:
图1为用于比较槭叶蚊子草的醇提取物和从其中分离出的溶剂提取部位的HMG-CoA还原酶抑制作用的图;
图2为示出了针对HMG-CoA还原酶的从槭叶蚊子草的乙酸乙酯提取部位中完全分离出的新化合物2的50%抑制浓度(IC50)的图;
图3为示出了使用油红O时细胞中脂质积累程度的图,表明对于从槭叶蚊子草的醇提取物中分离出的溶剂提取部位抑制泡沫细胞生成的效果,所述泡沫细胞是由于在巨噬细胞中引入氧化的LDL而形成的。
图4为条形图,示出了在从槭叶蚊子草的醇提取物中分离出的溶剂提取部位的不同浓度下,抑制泡沫细胞生成的效果,所述泡沫细胞是由于在巨噬细胞中引入氧化的LDL而形成的;
图5为新化合物1的1H NMR谱图,通过使用各种柱层析法从由槭叶蚊子草的醇提取物分离的乙酸乙酯提取部位中完全分离出所述新化合物1;
图6为新化合物1的13C NMR谱图,通过使用各种柱层析法从由槭叶蚊子草的醇提取物分离的乙酸乙酯提取部位中完全分离出所述新化合物1;
图7为新化合物1的HSQC NMR谱图,通过使用各种柱层析法从由槭叶蚊子草的醇提取物分离的乙酸乙酯提取部位中完全分离出所述新化合物1;
图8为新化合物1的HMBC NMR谱图,通过使用各种柱层析法从由槭叶蚊子草的醇提取物分离的乙酸乙酯提取部位中完全分离出所述新化合物1;
图9为新化合物2的1H NMR谱图,通过使用各种柱层析法从由槭叶蚊子草的醇提取物分离的乙酸乙酯提取部位中完全分离出所述新化合物2;
图10为新化合物2的13C NMR谱图,通过使用各种柱层析法从由槭叶蚊子草的醇提取物分离的乙酸乙酯提取部位中完全分离出所述新化合物2;
图11为新化合物2的HSQC NMR谱图,通过使用各种柱层析法从由槭叶蚊子草的醇提取物分离的乙酸乙酯提取部位中完全分离出所述新化合物2;以及
图12为新化合物2的HMBC NMR谱图,通过使用各种柱层析法从由槭叶蚊子草的醇提取物分离的乙酸乙酯提取部位中完全分离出所述新化合物2。
具体实施方式
除非上下文另有明确说明,否则在本说明书中代表成分,反应条件,聚合物组成和混合物量的所有数值,数字和/或表述均为近似值,反映了获得这些数字时固有地存在的各种测量不确定性。为此,应当理解,在所有情况下,术语“约”应修饰所有的数值,数字和/或表述。此外,当在说明书中公开数字范围时,除非另外定义,否则这些范围是连续的并且包括从最小值到最大值的所有数值,包括该范围内的最大值。此外,当范围是整数时,除非另外定义,否则它包括从最小值到最大值的所有整数,包括范围内的最大值。
应当理解的是,在说明书中,当涉及参数的范围时,该参数涵盖包括该范围内公开的端点在内的所有数字。例如,“5到10”的范围包括5、6、7、8、9和10的数字,以及任意子范围,如6到10、7到10、6到9和7到9的范围,以及落入该范围内的适当整数之间的任何数字,如5.5、6.5、7.5、5.5到8.5和6.5到9。另外,例如,“10%到30%”的范围涵盖了所有整数,这些整数包括10%,11%,12%和13%以及30%之类的数值,以及10%至15%,12%至18%或20%至30%的任意子范围,以及落入该范围内的适当整数之间的任何数值,如10.5%,15.5%和25.5%。
在下文中,将详细描述本发明。
本发明涉及一种用于制备食品组合物和治疗性药物组合物的方法,所述食品组合物和治疗性药物组合物含有槭叶蚊子草的叶的甲醇提取物和从中分离出的溶剂提取物以及新的化合物1和2,其通过抑制HMG-CoA还原酶(其为一种调节胆固醇合成速度的限速酶)的活性,并通过抑制泡沫细胞的形成(其表明动脉粥样硬化的早期阶段)用于降低血胆固醇水平和改善动脉粥样硬化。
本发明还涉及具有优异的降低血胆固醇水平和抑制泡沫细胞形成效果的槭叶蚊子草的提取物,其提取部位和从中分离出的活性化合物,所述泡沫细胞是由于在巨噬细胞中引入了氧化的LDL而形成的。
在另一方面,作为活性成分的所述组合物含有从槭叶蚊子草制得的醇提取物或从其中分离出的溶剂提取部位,或使用柱层析法通过一系列分离步骤从槭叶蚊子草的乙酸乙酯提取部位中完全分离出的新化合物1和2,特征在于具有抑制泡沫细胞形成和抑制HMG-CoA还原酶活性的优异效果,所述泡沫细胞是由于在巨噬细胞中引入了氧化的LDL而形成的。
除此之外,槭叶蚊子草提取物,其提取部位和从其中分离出的活性化合物具有清除自由基和抑制脂质过氧化的优异效果,因此可用于预防或治疗由氧化应激引起的衰老和各种疾病,如癌症,中风和帕金森氏病等脑部疾病,心脏病,局部缺血,动脉硬化,皮肤病,消化系统病,炎症,风湿病和自身免疫病。
根据本发明所述的用于制备槭叶蚊子草提取物及其提取部位的方法,包括步骤:
(步骤1)使用至少一种提取溶剂提取槭叶蚊子草以获得溶剂提取物的第一步,所述提取溶剂选自二氯甲烷,丙酮,丙酮水溶液,C1-4醇类和C1-4醇类水溶液;
(步骤2)使用水和乙酸乙酯提取第一步中获得的所述溶剂提取物以获得乙酸乙酯提取部位的第二步;和
(步骤3)通过柱层析法分离第二步中获得的所述乙酸乙酯提取部位,以获得新化合物1至2的第三步。
在获得所述溶剂提取物的第一步中使用的槭叶蚊子草可以是植物生长在地上或地下的任何部分,并且优选为地上部分,例如槭叶蚊子草的叶子、花或茎。收集的槭叶蚊子草可在阴凉处干燥,也可以切碎,粉化或冷冻干燥后再使用。
此处使用的所述提取溶剂可以是普通的有机溶剂,具体地可以包括选自二氯甲烷,丙酮,丙酮水溶液,C1-5醇类和C1-5醇类水溶液中的至少一种。更具体地,所述提取溶剂可以是二氯甲烷,丙酮,甲醇,丁醇,其混合溶剂,或包含20-80体积%水的其水溶液。
下面详细描述根据本发明的制备槭叶蚊子草提取物及其提取部位的方法的各个步骤。
每kg槭叶蚊子草添加0.1-5L,优选0.5-1.0L提取溶剂,并使其在室温下静置4至5天。该提取可以进行1至5次,或者必要时可以进行多次。另外,提取时的温度优选为10℃-100℃,更优选为室温,但不限于此。提取时间优选为1至7天,更优选为3至7天,但不限于此。过滤获得的提取物,减压浓缩,并干燥以获得溶剂提取物。所述减压浓缩优选使用真空旋转蒸发仪进行,但不限于此。另外,可以使用选自减压干燥,真空干燥,沸腾干燥,喷雾干燥,室温干燥和冷冻干燥中的一种来进行干燥,但不限于此。
在获得提取部位的第二步中,将以上获得的溶剂提取物用水和乙酸乙酯提取以获得乙酸乙酯提取部位。
更具体地,可以通过向1kg的溶剂提取物中添加1-5L,优选1.5-2.0L的水,向其中添加0.1-5L,优选1.0-1.5L的乙酸乙酯,并充分进行提取,以获得乙酸乙酯提取部位。
此外,在本发明中,即使通过用乙酸乙酯直接提取槭叶蚊子草而获得乙酸乙酯提取物,而无需使用有机溶剂获得溶剂提取物的第一步,也可以充分获得活性化合物。然而,为了获得更高纯度的活性化合物,优选在获得溶剂提取物的步骤1)之后按顺序实施获得乙酸乙酯提取部位的步骤。
在获得活性化合物的第三步中,对以上获得的乙酸乙酯提取部位进行柱层析。
所述槭叶蚊子草乙酸乙酯提取部位含有各种具有羟基的活性物质,如三萜类,单宁类和黄酮类。
通过填充选自由硅胶,Sephadex,RP-18,聚酰胺,Toyopearl和XAD树脂组成的组的填料进行柱层析,并且在本发明中对填料的选择没有特别限制。使用选自上述填料的合适填料进行柱层析。如果必要,可以使用适当选择的填料进行多次色谱分离。特别地,最优选使用Sephadex,RP-18和硅胶作为填料进行柱层析的适当组合。
通过柱层析法,能够分离出两种新化合物。
另外,本发明的特征在于,用于治疗、改善和预防高胆固醇血症,或由高胆固醇血症引起的心脏病或血管疾病的一种药物组合物或一种保健食品组合物,其包含作为活性成分的槭叶蚊子草的提取物或其提取部位。
通过上述活性化合物的分离方法获得所述槭叶蚊子草的提取物或其提取部位含有新化合物1至2的活性化合物,因此表现出显著的治疗、改善和预防高胆固醇血症或由高胆固醇血症引起的心脏病或血管疾病的效果。
另外,本发明的特征在于一种药物组合物或一种保健食品组合物,其包含槭叶蚊子草提取物或其溶剂提取部位作为活性成分。
槭叶蚊子草提取物或其溶剂提取部位表现出优异的抑制HMG-CoA还原酶活性和抑制由于巨噬细胞中掺入了氧化的LDL而引起的泡沫细胞形成的效果,因此可用作降低血胆固醇水平的药物组合物或保健食品组合物的活性成分。
也就是说,通过槭叶蚊子草提取物及其溶剂提取部位中的每一种产生的抑制HMG-CoA还原酶活性的作用和抑制泡沫细胞产生的作用可以治疗、预防或缓解的疾病或障碍,具体包括高胆固醇血症,高脂血症,动脉硬化,动脉粥样硬化,周围血管病,异常血脂症,高β脂蛋白血症,低α脂蛋白血症,高胆固醇血症,高甘油三酸酯血症,家族性高胆固醇血症,心血管障碍,冠心病,冠状动脉疾病,冠状血管病,心绞痛,局部缺血,心脏缺血,血栓症,心肌梗塞,中风,周围性血管疾病,再灌注损伤,血管成形术后再狭窄,高血压,充血性心力衰竭,糖尿病,糖尿病相关的血管并发症,肥胖症,内毒素血症等。
在下文中,将描述本发明的各个方面。
一方面,本发明提供了一种用于预防、改善或治疗心血管疾病的组合物,其包含槭叶蚊子草的提取物或其提取部位作为活性成分。
本文使用的植物槭叶蚊子草是一种多年生植物,其属于蔷薇科,其仅发现于韩国,包括庆尚道,京畿道,江原道和其他地区。槭叶蚊子草全身几乎没有毛,茎直立,细而长,高度约1m。叶子交替生长,并以棕榈(palm)的形式分成3至7个裂片,叶柄长。分开的部分是披针状的,末端尖锐,并且具有深凹陷的双重锯齿状,其长度和宽度约为20cm。叶柄有六对彼此交替生长的大和小羽毛形叶子,这些叶子可以省略,也可以只保留其痕迹。6月至8月,白花盛开于茎和枝末端的聚伞状花序中。几朵小花聚集成掸子的形状。因此,这种植物被称为“掸子草”。将嫩叶轻轻煮沸并调味,或将蔬菜在热水中煮沸,然后在阳光下干燥用于以干燥形式使用。
如本文所用的术语“提取物”是指通过从来自天然产物的提取成分获得的任何物质,而与提取方法或成分类型无关。例如,从广义上说,提取物包括通过使用水或有机溶剂从天然产物中提取可溶于溶剂的成分而获得的物质,或仅从天然产物中提取一种特定成分而获得的物质等。在本发明的一个实施方案中,对有机溶剂没有特别限制,并且其可以选自:C1-C5低级醇,如甲醇,乙醇,异丙醇,正丙醇,正丁醇和异丁醇;多元醇,如甘油,乙二醇,丙二醇和1,3-丁二醇;烃类溶剂,如乙酸甲酯,乙酸乙酯,苯,正己烷,乙醚,二氯甲烷,氯仿;以及非极性有机溶剂,如石油醚,乙酸甲酯,苯,己烷,氯仿,二氯甲烷,二甲醚和乙酸乙酯。
在另一方面,本发明提供了一种抗氧化剂组合物,其包含槭叶蚊子草提取物或其提取部位作为活性成分。
在另一方面,本发明提供了一种用于降低血液中胆固醇的组合物,其包含槭叶蚊子草提取物或其提取部位作为活性成分。
在另一方面,本发明提供了一种用于抑制泡沫细胞生成的组合物,其包含槭叶蚊子草提取物或其提取部位作为活性成分。
在本发明的一方面,所述槭叶蚊子草提取物是槭叶蚊子草的地上部分或地下部分的提取物。
在本发明的一方面,所述提取物是通过用水,C1-C5醇类,丙酮,丙酮水溶液或C1-C5醇类水溶液提取而获得的提取物。
在本发明的一方面,所述C1-C5醇类包括选自由甲醇,乙醇,异丙醇,正丙醇,正丁醇和异丁醇组成的组中的至少一种。
在本发明的一方面,所述C1-C5醇类水溶液和所述丙酮水溶液的浓度各自独立地为10%至90%(v/v)。
在本发明的一方面,所述槭叶蚊子草提取物可以以所述组合物总重量的0.001-90wt%的含量存在。在一个实施方案中,所述槭叶蚊子草提取物可以以所述组合物总重量的0.001wt%或更多,0.01wt%或更多,0.1wt%或更多,1wt%或更多,1.1wt%或更多,1.5wt%或更多,2wt%或更多,3wt%或更多,5wt%或更多,10wt%或更多,20wt%或更多,或30wt%或更多的含量存在。另外,所述槭叶蚊子草提取物可以以所述组合物总重量的90wt%或更少,85wt%或更少,80wt%或更少,70wt%或更少,50wt%或更少,40wt%或更少,30wt%或更少,20wt%或更少,10wt%或更少,5wt%或更少,4wt%或更少,3wt%或更少,2wt%或更少,1wt%或更少,0.1wt%或更少,或0.05wt%或更少的含量存在。
在本发明的一方面,所述提取部位为槭叶蚊子草C1-C5醇类提取物的乙酸乙酯提取部位。
根据本发明一方面的用于预防、改善或治疗心血管疾病的组合物通过抑制HMG-CoA还原酶活性,抑制泡沫细胞生成和抑制脂质过氧化物生成中的至少一种来预防、缓解或治疗心血管疾病。
根据本发明一方面的抗氧化剂组合物通过清除自由基,抑制超氧阴离子生成和抑制脂质过氧化物生成中的至少一种来表现出抗氧化作用。
根据本发明的一方面的用于改善心血管疾病的组合物,抗氧化剂组合物,用于降低胆固醇的组合物或用于抑制泡沫细胞形成的组合物为保健食品组合物。
根据本发明的一方面的用于用于预防、改善或治疗心血管疾病的组合物为药物组合物。
在本发明的一方面,所述药物组合物以注射剂,粉剂,颗粒剂,片剂,胶囊剂,混悬剂,乳剂,糖浆剂,气雾剂和外用制剂中的任何一种形式配制。
在本发明的一方面,所述心血管疾病可包括选自由高胆固醇血症,高脂血症,动脉硬化,动脉粥样硬化,周围血管病,异常血脂症,高β脂蛋白血症,低α脂蛋白血症,高胆固醇血症,高甘油三酸酯血症,家族性高胆固醇血症,心血管障碍,冠心病,冠状动脉疾病,冠状血管病,心绞痛,局部缺血,心脏缺血,血栓症,心肌梗塞,中风,周围性血管疾病,再灌注损伤,血管成形术后再狭窄,高血压,充血性心力衰竭,糖尿病,糖尿病相关的血管并发症,肥胖症,内毒素血症等组成的组中的至少一种。
根据本发明所述的药物组合物可以通过进一步包含常用于制备药品的合适的载体,赋形剂和/或稀释剂,以适于口服或肠胃外给药的药物制剂的形式制备。此外,药物制剂可以使用本发明的药物组合物根据常规方法制备。在制剂的制备中,活性成分可以与载体混合,用载体稀释或以胶囊、小袋或其他容器的形式封闭在载体中。因此,所述制剂可以是片剂,丸剂,粉剂,胶囊剂,小袋剂,酏剂,混悬剂,乳剂,液体剂,糖浆剂,气雾剂,软或硬明胶胶囊剂,注射用溶液或混选液,软膏剂,乳膏剂,凝胶剂,洗剂等。
可以包括在本发明的药物组合物中的合适的载体,赋形剂和稀释剂的例子包括:乳糖,右旋糖,蔗糖,山梨糖醇,甘露糖醇,硅酸钙,纤维素,甲基纤维素,微晶纤维素,聚乙烯吡咯烷酮,水,羟基苯甲酸甲酯,羟基苯甲酸丙酯,滑石粉,硬脂酸镁和矿物油。另外,可以进一步包括在制剂的制备中常用的填充剂,抗凝剂,润滑剂,润湿剂,香料,乳化剂,防腐剂等。可以使用本领域公知的方法配制本发明所述的药物组合物,以在向哺乳动物给药后提供活性成分的快速、持续或延缓释放。
根据本发明的药物组合物的给药途径的例子包括但不限于口服给药,静脉内给药,肌内给药,动脉内给药,髓内给药,鞘内给药,心内给药,透皮给药,皮下给药,腹膜内给药,肠道给药,舌下给药或局部给药。
本发明所述的药物组合物的剂量可以根据患者的状况和体重,疾病的严重程度,药物形式,给药途径和给药持续时间而改变,并且可以由本领域技术人员适当地选择。相对于患者体重的活性成分可以在0.001mg/kg至500mg/kg的范围内,优选地在0.001至200mg/kg的范围内。给药可以每天一次,也可以分批几次。所述剂量在任何方面均不限制本发明的范围。
在另一方面,本发明提供了一种以下式1表示的新化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物:
[式1]
在另一方面,本发明提供了一种以下式2表示的新化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物:
[式2]
如本文所使用的,术语“异构体”不仅包括光学异构体(例如,基本纯的对映异构体,基本纯的非对映异构体或其混合物),而且包括构象异构体(即,仅在一个或多个化学键的角度上存在不同的异构体),位置异构体(特别是互变异构体)或几何异构体(例如,顺反异构体)。
如本文所使用的,术语“基本纯的”是指当例如与对映异构体或非对映异构体结合使用时,作为对映异构体或非对映异构体例子提供的特定化合物的存在量为约90%或更高,优选约95%或更高,更优选约97%或更高,甚至更优选约98%或更高,甚至更优选约99%或更高,且再更优选约99.5%或更高(w/w)。
如本文所使用的,术语“药学上可接受的”是指,通过在动物(尤其是人类)中以常见药物剂量使用一种物质时避免明显的毒性作用,该物质在动物(尤其是人类)中的使用可以在政府或与之等效的监管机构获得批准或已被批准,或列在药典中,或公认已在其他一般药典中进行了描述。
如本文所使用的,术语“药学上可接受的盐”是指根据本发明一方面的盐,其是药理学上可接受的并且表现出其母体化合物的所需的药理活性。所述盐可包括:(1)由无机酸(如盐酸,氢溴酸,硫酸,硝酸或磷酸)形成的酸加成盐;由有机酸(如乙酸,丙酸,己酸,环戊基丙酸,乙醇酸,丙酮酸,乳酸,丙二酸,琥珀酸,苹果酸,马来酸,富马酸,酒石酸,柠檬酸,苯甲酸,3-(4-羟基苯甲酰基)苯甲酸,肉桂酸,扁桃酸,甲磺酸,乙磺酸,1,2-乙二磺酸,2-羟基乙磺酸,苯磺酸,4-氯苯磺酸,2-萘磺酸,4-甲苯磺酸,樟脑磺酸,4-甲基二环-[2.2.2]辛-2-烯-1-羧酸,葡萄糖庚酸,3-苯基丙酸,三甲基乙酸,叔丁基乙酸,月桂基硫酸酯,葡萄糖酸,谷氨酸,羟基萘甲酸,水杨酸,硬脂酸和粘康酸)形成的酸加成盐;或者(2)通过取代母体化合物中存在的酸性质子形成的盐。
如本文所使用的,术语“水合物”是指一种与水结合的化合物,并且从广义上说,包括水与该化合物之间没有化学键合力的所包括的化合物。
如本文所使用的,术语“溶剂化物”是指在溶质的分子或离子与溶剂的分子或离子之间形成的高级化合物。
在另一方面,本发明提供了一种用于预防、改善或治疗心血管疾病的组合物,其包含根据式1或2的化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物作为活性成分。
在一个实施方案中,用于预防、改善或治疗心血管疾病的组合物可以是一种药物组合物。
在本发明的一个实施方案中,所述药物组合物以注射剂,粉剂,颗粒剂,片剂,胶囊剂,混悬剂,乳剂,糖浆剂,气雾剂和外用制剂中的任何一种形式配制。
在本发明的一个实施方案中,所述心血管疾病可包括选自由高胆固醇血症,高脂血症,动脉硬化,动脉粥样硬化,周围血管病,异常血脂症,高β脂蛋白血症,低α脂蛋白血症,高胆固醇血症,高甘油三酸酯血症,家族性高胆固醇血症,心血管障碍,冠心病,冠状动脉疾病,冠状血管病,心绞痛,局部缺血,心脏缺血,血栓症,心肌梗塞,中风,周围性血管疾病,再灌注损伤,血管成形术后再狭窄,高血压,充血性心力衰竭,糖尿病,糖尿病相关的血管并发症,肥胖症和内毒素血症组成的组中的至少一种。
在一个实施方案中,用于改善心血管疾病的组合物可以是一种保健食品组合物。
根据本发明所述的保健食品组合物含有槭叶蚊子草的提取物或从其中分离出的溶剂提取部位,并且对其类型没有特别限制。食品的例子包括饮品,肉,香肠,面包,饼干,年糕,Sunsik(用谷物制成的韩国即食食品),巧克力,糖果,零食,甜点,比萨,拉面,其他面条,口香糖,乳制品(包括冰淇淋),各种汤,饮料,酒精饮料,维生素复合物,乳制品和加工过的乳制品,以及包括所有常规意义上的其他功能性保健食品。作为活性成分,所述槭叶蚊子草的提取物或从其中分离出的溶剂提取部位可以单独添加到食品中,也可以与其他食品或食品成分一起使用,并且可以根据常规方法适当使用。有效含量可以根据使用目的(用于预防或改善)适当地确定,并且可以在相对于保健食品总重量的0.001至70wt%的范围内存在。然而,在出于健康和卫生目的或为了健康控制而长期摄入的情况下,该量可以低于上述范围,并且可以以高于上述范围的量使用活性成分,因为在安全方面没有问题。例如,在制备保健饮料的情况下,除了活性成分外,该保健饮料还可以包含天然碳水化合物或调味剂作为饮料制备中常用的添加剂。该天然碳水化合物可包括常规的糖,如单糖(例如葡萄糖,果糖等),二糖(例如麦芽糖,蔗糖等)和多糖(例如糊精,环糊精等),以及糖醇,如木糖醇,山梨糖醇和赤藓糖醇。相对于该保健食品的总重量,该天然碳水化合物可以在1-20wt%,优选5-10wt%的范围中存在。该调味剂可包括天然调味剂(奇异果甜蛋白,甜菊提取物,莱鲍迪甙A,甘草甜素等)和合成调味剂(糖精,阿斯巴甜等)。该保健食品可含有其他营养素,维生素,矿物质(电解质),香料(合成或天然香料),着色剂,果胶酸及其盐,藻酸及其盐,有机酸,保护性胶体增稠剂,pH调节剂,稳定剂,防腐剂,甘油,酒精,碳酸饮料中使用的碳酸等。另外,它可以包含用于生产天然果汁,果汁饮料和蔬菜饮料的果肉。这些添加剂的含量没有特别限制,但相对于保健食品的总重量,可以在0.1-20wt%的范围内。
在另一方面,本发明提供了一种用于获得抗氧化作用的保健食品组合物,其包含根据式1或2的化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物作为活性成分。
在另一方面,本发明提供了一种用于降低血胆固醇水平的保健食品组合物,其包含根据式1或2的化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物作为活性成分。
在另一方面,本发明提供了一种用于抑制泡沫细胞形成的保健食品组合物,其包含根据式1或2的化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物作为活性成分。
在另一方面,本发明提供了一种根据式1或2的化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物,其中,根据式1或式2的所述化合物是从槭叶蚊子草中分离出的成分。
在下文中,将参考具体实施例更详细地描述本发明。然而,以下实施例仅用于示例性说明本发明,而不应解释为限制本发明的范围。
[实施例]
实施例1槭叶蚊子草叶的提取物或提取部位的制备
将6L甲醇添加到收集的槭叶蚊子草的叶子(干重840g)中,并在室温下进行提取一周。重复该过程三遍后,将所得产物过滤并在40℃下用旋转浓缩器浓缩至干,得到194.6g甲醇提取物。将甲醇提取物悬浮于2,000mL水中,然后用二氯甲烷提取(2,000ml×3)。用乙酸乙酯(2,000mL×3)提取水层以获得乙酸乙酯提取部位。然后,将水层再次用丁醇(2,000mL×3)提取以获得丁醇提取部位。
实施例2槭叶蚊子草茎的提取物或提取部位的制备
将2L甲醇添加到收集的槭叶蚊子草的茎(干重300g)中,并在室温下进行提取一周。重复该过程三遍后,将所得产物过滤并在40℃下用旋转浓缩器浓缩至干,得到42.13g甲醇提取物。将甲醇提取物悬浮于400mL水中,然后用二氯甲烷提取(400mL×3)。用乙酸乙酯(400mL×3)提取水层以获得乙酸乙酯提取部位。然后,将水层再次用丁醇(400mL×3)提取以获得丁醇提取部位。
实施例3槭叶蚊子草花的提取物或提取部位的制备
将600mL甲醇添加到收集的槭叶蚊子草的花(干重67.8g)中,并在室温下进行提取一周。重复该过程三遍后,将所得产物过滤并在40℃下用旋转浓缩器浓缩至干,得到25.3g甲醇提取物。将甲醇提取物悬浮于250mL水中,然后用二氯甲烷提取(250mL×3)。用乙酸乙酯(250mL×3)提取水层以获得乙酸乙酯提取部位。然后,将水层再次用丁醇(250mL×3)提取以获得丁醇提取部位。
实施例4从乙酸乙酯提取部位中分离出新化合物1和2
将12.5g实施例1中获得的槭叶蚊子草叶的乙酸乙酯提取部位用Sephadex LH-20柱色谱进行柱层析(7×26cm)。使用甲醇作为展开剂,用正相硅胶TLC(展开剂:二氯甲烷/甲醇/水=50/10/1)观察得到的提取部位,然后收集具有相似极性的化合物并将其分为11个子提取部位(EA-EI1)。
将子提取部位E3(4.1g)溶于甲醇,过滤掉不溶的固体,并将滤液反复进行柱层析和反相硅胶柱层析(40%甲醇),以获得8.7mg新化合物1。
通过Sephadex LH-20柱色谱,使用甲醇作为展开剂,将子提取部位E8(792.9mg)分为三个子提取部位(E8a至E8c)。将子提取部位E8b(721.2mg)进行柱层析,使用40%甲醇作为展开剂,并使用反相硅胶作为固定相。通过TLC收集相似的化合物,并将其分为8个子提取部位(E8b1至E8b8)。使用Toyopearl HW-40C和制备型HPLC,从第一子提取部位E8b1(543.7mg)获得了新化合物2(20.6mg)。
实施例5新化合物的结构表征
使用400MHz(1H)和100MHz(13C)获得从由槭叶蚊子草醇提取物中分离出的乙酸乙酯提取部位分离得到的新化合物的NMR谱图,并且每个峰的化学位移表示为内标三甲基硅烷的相对值。用于新化合物结构分析的1H NMR,13C NMR,HSQC和HMBC谱图如图5至12所示。
(1)化合物1的结构确定
6’-没食子酰基野蔷薇苷
本发明的化合物1的化学性质如下。
——无定形白色粉末
——HR-ESI-TOP-MS(阳离子模式)m/z 825.4020[M+Na]+
(计算得出825.4037,C43H62O14Na)
——1H NMR(400MHz,CD3OD):δ0.665(s,3H,H-26),0.761(s,6H,H-25,24),0.936(d,3H,J=6.8Hz,H-30),0.982(s,3H,H-23),1.194(s,3H,H-29),1.296(s,3H,H-27),2.566(s,1H,H-18),2.886(d,1H,J=9.6Hz,H-3),3.368-3.484(3H,m,H-2',3',4'),3.558-3.593(m,1H,H-2),3.672(m,1H,H-5'),4.337(dd,1H,J=5.6,12.0Hz,H-6a'),4.405(dd,1H,J=2.0,12.0Hz,H-6b'),5.290(brt,1H,H-12),5.402(d,1H,J=8.0Hz,H-1'),7.095(s,2H,H-2",6")。
——13C NMR(100MHz,CD3OD):δ16.55(C-30),16.95(C-25),17.39(C-24),17.94(C-26),17.41(C-6),24.66(C-11),24.81(C-27),26.42(C-16),26.93(C-29),27.05(C-21),29.25(C-15,23),33.88(C-7),38.42(C-22),38.95(C-10),40.38(C-4),41.20(C-8),42.39(C-14),42.60(C-20),48.35(C-1),48.78(C-9,与溶剂重叠),49.63(C-17),54.60(C-18),56.57(C-5),65.05(C-6'),69.53(C-2),71.45(C-4'),73.65(C-2'),73.78(C-19),75.77(C-5'),78.14(C-3'),95.51(C-1'),110.39(C-2",6"),121.28(C-1"),129.70(C-12),139.46(C-4"),139.84(C-13),146.42(C-3",5"),168.56(C-7"),178.85(C-28)。
化合物1为乌苏烷型三萜,具有以下结构:其中2和19位分别被羟基取代,并且,具有与葡萄糖6键合的没食子酰基的取代基酯键合在乌苏酸的28位上。它是一种新颖的化合物,在本研究中,第一次将它从自然界分离出来并对其结构进行了阐明。
(2)化合物2的结构确定
皱褶菌素B甲酯
本发明的化合物2的化学性质如下。
——无定形浅棕色粉末
——HR-ESI-TOP-MS(阳离子模式)m/z 991.1015[M+Na]+
(计算得出991.1028,C42H32O27Na)
——1H NMR(400MHz,CD3OD):δ3.741,3.752(s,Hα-OMe,Hβ-OMe),3.769,3.848(d,J=13.6Hz,Hα-glc6,Hβ-glc6),4.180(m,Hβ-glc5),4.609(m,Hα-glc5),5.068(d,J=7.6Hz,Hβ-glc1),5.099(m,Hα-glc4,Hβ-glc4),5.113(dd,J=3.6,10.0Hz,Hα-glc2),5.187(br t,J=7.6,8.4Hz,Hβ-glc2),5.252(dd,J=6.8,13.6Hz,Hα-glc6),5.338(dd,J=6.0,13.6Hz,Hβ-glc6),5.477(d,J=3.6Hz,Hα-glc1),5.852(t,J=9.6Hz,Hβ-glc3),5.857(t,J=10.0Hz,Hα-glc3),6.192,6.481(s,β-端基差向异构体valoneoyl-3,3'),6.198,6.522(s,α-端基差向异构体valoneoyl-3,3'),6.913,7.018(s,β-端基差向异构体没食子酰基-2,6),6.948,7.038(s,α-端基差向异构体没食子酰基-2,6),6.953(s,β-端基差向异构体valoneoyl-6"),7.062(s,α-端基差向异构体valoneoyl-6")。
——13C NMR(100MHz,CD3OD):δ52.48(C-OMe),64.23,64.31(Cα,β-glc6),67.49(Cα-glc5),71.66(Cβ-glc4),71.95,72.01(Cα-glc3,4),72.69(Cβ-glc2),73.44(Cα-glc2),74.31(Cβ-glc5),74.70(Cβ-glc3),91.72(Cα-glc1),97.01(Cβ-glc1),106.02,106.08,108.08(Cα,β-valoneoyl-3,3'),109.93(Cα,β-valoneoyl-6"),110.34,110.39,110.44(Cα,β-没食子酰基-2,6),115.06(Cα,β-valoneoyl-1),116.22,118.53(Cα,β-valoneoyl-1,1'),120.56,120.85,120.80,120.87(Cα,β-没食子酰基-1,1'),125.67,125.74,125.91,125.93(Cα,β-valoneoyl-2,2'),137.59,137.61,137.66,137.69(Cα,β-valoneoyl-5,4"),138.27(Cα,β-valoneoyl-5'),139.94,139.98,140.01,140.15(Cα,β-没食子酰基-4,4'),140.82,140.87(Cα,β-valoneoyl-2",3"),143.83(Cα,β-valoneoyl-5"),144.97(Cα,β-valoneoyl-6),145.33,145.36(Cα,β-valoneoyl-6'),145.99(Cα,β-valoneoyl-4),146.19,146.21(Cα,β-没食子酰基-3,5),146.35,146.38(Cα,β-没食子酰基-3',5'),147.61,147.67(Cα,β-valoneoyl-4'),167.10(Cβ-没食子酰基-7),167.47(Cα-没食子酰基-7),167.63(Cα,β-valoneoyl-7"),167.70(Cβ-没食子酰基-7'),167.93(Cα-没食子酰基-7'),169.14,169.22(Cβ-valoneoyl-7,7'),169.29,169.40(Cα-valoneoyl-7,7')。
化合物2为可水解的单宁,具有以下结构:其中没食子酰基分别键合至葡萄糖2和3,valoneoyl基团分别键合至葡萄糖4和6,并且,甲基酯键合在valoneoyl基团7,并且为互变异构体,其中α-端基差向异构体和β-端基差向异构体在葡萄糖部分的1位上具有未取代的羟基。化合物2是通过化学变化产生的化合物,用于分离自匍匐大戟(Euphorbiaprostrata)和檵木(Loropetalum chinense)的酪氨酸激酶抑制剂B中的结构分析。它是一种新颖的化合物,在本研究中,第一次将它从自然界分离出来并对其结构进行了阐明。
实验例1HMG-CoA还原酶抑制作用实验
1)试剂和设备
次亚磷酸钠,二磷酸钠,DL-HMG-CoA钠盐水合物,还原的β-烟酰胺腺嘌呤二核苷酸2'-磷酸(NADPH),普伐他汀,NaCl,DL-二硫苏糖醇(DTT),二甲基亚砜(DMSO),乙二胺四乙酸(EDTA)和HMG-CoA还原酶(712μg/ml)购自Sigma-Aldrich(密苏里州圣路易斯)。透明的96孔板购自SPL Lifesciences(Pocheon)。使用了来自Molecular Devices的VERSA MaxTM酶标仪。
2)检测HMG-CoA还原酶抑制作用的方法
使用Perchellet分析方法(Int.J.Mol.Med.,2009,24,633)的略微修改模式评估HMG-CoA还原酶的抑制作用。使用前将待检测样品溶解在DMSO中。也就是说,将100mM NaCl,1mM EDTA,10mM DTT和10mM NADPH添加到96孔板中,将待检测样品添加至100mM磷酸钠缓冲液(pH 6.8)中,并向其中添加10.2μg/ml的HMG-CoA还原酶(8mM,终浓度)以开始反应。
通过使用VERSA MaxTM酶标仪在37℃下10分钟于340nm处记录吸光度,比较和分析HMG-CoA还原酶的活性。使用DMSO作为对照,并使用100μM普伐他汀作为阳性对照。实验重复了三遍。
在各种浓度下检测到槭叶蚊子草叶的醇提取物和从其溶剂提取部位获得的二氯甲烷提取部位(308-44AD),乙酸乙酯提取部位(308-44AE)和丁醇提取部位(308-44AB)对HMG-CoA还原酶的抑制作用。检测结果如下表1和图1中所示。
[表1]
从表1和图1可以看出,槭叶蚊子草提取物或其溶剂提取部位对HMG-CoA还原酶具有非常出色的IC50值,其为1.46至3.67μg/ml。用于比较提取物效果的对照药物是普伐他汀,其目前在临床实践中使用。该对照药物的IC50值为0.40±0.04μM。虽然,难以将其功效与单一物质进行比较,考虑到槭叶蚊子草提取物是混合物这一事实,槭叶蚊子草提取物或其提取部位表现出相当有效的作用。
同时,新化合物1对HMG-CoA还原酶的IC50值为175.2±2.2μg/ml,如表1所示,而新化合物2对HMG-CoA还原酶的优异的IC50值为1.46±0.22μg/ml,如表1和图2所示。这意味着该化合物显示出优异的效果,因此作为从可食用的天然产物中分离出的化合物用于开发可替代他汀类药物(据报道会其引起许多副作用)的原料,具有开发成为天然药物的巨大潜力。
实验例2槭叶蚊子草提取物的抗氧化作用实验
1)DPPH自由基清除作用的检测
通过将实施例中获得的测试样品添加到190μl的100μM 1,1-二苯基-2-苦基肼基(DPPH)乙醇溶液中,在37℃下反应30分钟,并测量515nm处的吸光度而将自由基清除作用(Blois等人,自然,1958,181,1199)评估为IC50。IC50的意思是,在计算自由基清除活性时获得50%的自由基清除的浓度(SC 50)。数据表示为平行三次重复测量的平均值。
2)槭叶蚊子草提取物对黄嘌呤/黄嘌呤氧化酶诱导的超氧阴离子(O2·-)的清除作用的检测
Toda等人的以下方法(Planta,Med.57:8,1991)用于评估抑制超氧阴离子生成的作用,该超氧阴离子是由黄嘌呤和黄嘌呤氧化酶(XOD)反应产生的。具体地,将0.1mM黄嘌呤,0.1mM EDTA,50μg/ml牛血清白蛋白(BSA),25mM的氮蓝四唑(NBT),40mM的Na2CO3溶液,在每种浓度下稀释的测试样品溶液和最终体积为200μl的含有1.4×10-3单位XOD的溶液混合并在25℃下反应20分钟。向反应溶液中加入6.6μl的6mM CuCl2终止反应后,在560nm处测量所形成的甲瓒的吸光度,并将黄嘌呤/黄嘌呤氧化酶诱导的超氧阴离子清除作用的比较结果计算为IC50。IC50是指在计算黄嘌呤/黄嘌呤氧化酶诱导的超氧阴离子清除活性时获得50%的黄嘌呤/黄嘌呤氧化酶诱导的超氧阴离子清除的浓度(SC50),并且数据表示为平行三次进行测量的平均值。
3)槭叶蚊子草提取物抑制脂质过氧化物形成的作用
检测了提取物和分离的化合物对脂质过氧化物生成的抑制作用(LPO)。脂质过氧化物是通过各种氧化反应使脂质过氧化而生成的物质。活性氧,自由基等氧化含有大量不饱和脂肪酸的细胞膜磷脂,从而在细胞膜上生成脂质过氧化物。当脂质过氧化物积聚在细胞膜中时,细胞膜的流动性和功能性恶化,导致组织局部紊乱,例如抑制细胞功能和改变细胞结构。
因此,在下文中检测了槭叶蚊子草叶和茎提取物以及分离出的化合物对脂质过氧化物生成的抑制作用。实验中使用的动物是雄性Sprague-Dawley大鼠,实验前只喂水24小时。该实验是根据韩国科学技术研究所的动物研究伦理委员会批准的(批准文号:KISTIACUC-2018-081)实验室动物管理和使用指南进行的。用异氟烷对实验动物进行呼吸麻醉,并将其解剖,并通过肝门静脉灌注0.15M冰冷的KCl溶液,以从肝脏中去除血液并提取肝脏。通过用肝脏重量10倍量的KCl溶液进行均质化以制备肝脏匀浆,以牛血清白蛋白为标准,通过Bradford蛋白质法(Bradford,MM Anal.Biochem.72,248,1976)对蛋白质浓度进行定量。使用Sanz等人的方法(Sanz,M.J.,et al.,Xenobiotica 24,689-69,1994)的稍微修改的模式进行脂质过氧化测试。将50mM Tris-HCl缓冲液(pH 7.5)添加至300μl肝脏匀浆(11mg蛋白质/ml),10μM FeSO4,10μl测试药物和0.4mM抗坏血酸中以将总体积调节至1ml,然后,将所得混合物在37℃下孵育30分钟。孵育后,向其中加入2ml的TBA-TCA溶液(0.375%硫代巴比妥酸,15%三氯乙酸,0.25N HCl,0.01%丁羟甲苯),使其在95℃下反应30分钟,然后冷却并离心(5,000×g)10分钟,并在535nm处测量上清液的吸光度。将水飞蓟素,白藜芦醇和槲皮素用作对照药物,以比较脂质过氧化抑制作用。作为对照,使用DMSO代替测试药物,并测量了抑制脂质过氧化物形成50%所需的样品的浓度(IC50),结果示于下表2中。
[表2]
关于DPPH自由基清除活性,超氧阴离子自由基清除活性和脂质过氧化物生成的抑制活性,它们被检测为对血管保护具有重要意义的抗氧化活性,所述槭叶蚊子草提取物和溶剂提取部位也表现出优异的抗氧化作用,如表2所示。也就是说,来自槭叶蚊子草醇提取物的溶剂提取部位——乙酸乙酯提取部位和丁醇提取部位具有4.07-6.27μg/ml的50%自由基清除活性(SC50),因此与作为对照药物的抗坏血酸,槲皮素和白藜芦醇(众所周知的抗氧化物质)的自由基清除活性(SC50)相比,具有优异的效果。关于使用大鼠肝脏匀浆抑制脂质过氧化物生成的作用,从来自所述槭叶蚊子草醇提取物的溶剂提取部位得到的乙酸乙酯提取部位的50%抑制活性(IC50)为9.67±0.14μg/ml,其比水飞蓟素作为肝脏保护剂的抑制活性(IC50)98.7±0.02μg/ml高约10倍,比槲皮素的抑制活性(IC50)29.57±1.32μg/ml高约3倍。
实验例3槭叶蚊子草提取物对巨噬细胞中泡沫细胞形成的抑制作用
1)细胞培养与处理条件
细胞是购自ATCC公司的人单核细胞THP-1,并在高葡萄糖DMEM+10%FBS+1%P/S的培养基条件下培养,氧化的LDL(ox-LDL)购自Invitrogen。通过使用浓度为5μM的作为阳性对照的普伐他汀处理以进行实验。也就是说,将THP-1细胞在1%FBS中保存6小时,用对照和测试物质处理,并在2小时后,进一步用25μg/ml的ox-LDL处理。16小时后,将细胞用4%多聚甲醛固定并进行油红O染色,将用于染色细胞的试剂用100%异丙醇洗脱,并在450nm的波长处测量吸光度。结果显示在图3和4中。
众所周知,在动脉粥样硬化的早期,单核细胞等会通过粘附的分子物质分化为巨噬细胞,而该巨噬细胞利用清道夫受体将修饰的LDL内在化,然后转化为泡沫细胞,所述泡沫细胞使脂质沉积在血管中,从而导致动脉硬化。从图3和图4可以看出,所述槭叶蚊子草提取物和溶剂提取部位以浓度依赖的方式表现出优异的抑制泡沫细胞形成的作用。特别是,所述槭叶蚊子草乙酸乙酯溶剂提取部位(Fg-AE)和丁醇提取部位(Fg-AB)表现出非常出色的抑制泡沫细胞形成的作用,与目前临床上使用的对照药物普伐他汀的作用相当,因此具有被开发为有助于预防血管疾病(例如动脉硬化)的天然材料的巨大潜力。
如上所述,根据本发明的槭叶蚊子草提取物及其溶剂提取部位中的每一种都表现出抗氧化作用,以及显著的抑制HMG-CoA还原酶,抑制巨噬细胞中的泡沫细胞形成和降低血液中胆固醇浓度的效果,因此,可用作药物组合物或保健食品组合物中的活性成分,用于治疗、预防和改善高胆固醇血症或由高胆固醇血症引起的心脏病或血管疾病。
[制备实施例]
同时,根据本发明的含有槭叶蚊子草提取物或其溶剂提取部位的药物组合物可以根据其目的以各种形式制备。以下制备例1至4描述了根据本发明的制备包含槭叶蚊子草提取物或其溶剂提取部位作为活性成分的药物的方法,但是本发明不限于此。
制备例1:片剂(直接压片)
将5.0mg活性成分过筛,并与14.1mg乳糖,0.8mg交聚维酮USNF和0.1mg硬脂酸镁混合,并将混合物压制成片剂。
制备例2:片剂(湿法制粒)
将5.0mg活性成分过筛,并与16.0mg乳糖和4.0mg淀粉混合。将0.3mg的聚山梨酯80溶解于纯水中,并将适量的所得溶液添加至混合物中,然后制粒。干燥颗粒,过筛并与2.7mg胶体二氧化硅和2.0mg硬脂酸镁混合。将颗粒压制成片剂。
制备例3.粉剂和胶囊
将5.0mg活性成分过筛,然后与14.8mg乳糖,10.0mg聚乙烯吡咯烷酮和0.2mg硬脂酸镁混合。使用合适的装置将所得混合物填充于硬质5号明胶胶囊。
制备例4.注射剂
通过掺入100mg活性成分以及180mg甘露糖醇,26mg Na2HPO4·12H2O和2,974mg蒸馏水以制备注射剂。
另外,含有所述槭叶蚊子草提取物及其溶剂提取部位的根据本发明的保健食品组合物可以根据其目的以各种形式制备。以下制备例5至9描述了根据本发明的制备包含槭叶蚊子草提取物或其溶剂提取部位作为活性成分的保健食品的方法,但是本发明不限于此。
制备例5.颗粒保健食品
将1,000mg活性成分,70g维生素A醋酸酯,1.0mg维生素E,0.15mg维生素B2,0.5mg维生素B6,0.2mg维生素B12,10mg维生素C,10μg生物素,1.7mg烟酰胺,50μg叶酸,0.5mg泛酸钙,1.75mg硫酸亚铁,0.82mg氧化锌,25.3mg碳酸镁,15mg磷酸二氢钾,55mg磷酸氢钙,90mg柠檬酸钾,100mg碳酸钙和24.8mg氯化镁进行混合,然后按照常规方法制备颗粒保健食品。
制备例6.保健饮料
将1,000mg活性成分,1,000mg柠檬酸,100g低聚糖,2g李子浓缩物和1g牛磺酸混合,并向其中添加纯净水以将总体积调节至900ml。
在85℃加热并搅拌约1小时后,将所得溶液过滤并装入灭菌的2升容器中,并将该容器密封并灭菌以制备保健饮料。
尽管在优选实施例中上述组合物配比是作为适合于优选饮料的组分的混合物而获得的,混合比例可以根据地区和种族偏好(例如目标客户,目标县和用途)任意修改。
制备例7.面粉食品
将0.5-5g活性成分添加到100g面粉中,并使用所得混合物制备面包,蛋糕,小甜饼,饼干和面条,以制备用于改善健康的食品。
制备例8.乳制品
将5-10g活性成分添加到100g牛奶中,并使用该牛奶制备各种乳制品,如黄油和冰淇淋。
制备例9.Sunsik(用谷物制成的韩国即食食品)
通过已知方法将30g糙米,20g大麦,10g糯米和15g薏仁预胶化,干燥并烘烤,然后用研磨机制备成粒度为60目的粉末。通过已知方法将7g黑豆,7g黑芝麻种子和7g紫苏籽蒸熟,然后干燥,烘烤,再用研磨机制备成粒度为60目的粉末。将以上制得的谷物和种子与3g本发明的活性成分混合以制备Sunsik。
从上述内容可以明显看出,通过本发明获得的所述槭叶蚊子草醇提取物和从其中分离出的溶剂提取部位,或从槭叶蚊子草的乙酸乙酯提取部位中完全分离出的新化合物1和2,具有对HMG-CoA还原酶活性的优异抑制作用,优异的抗氧化作用以及显著优异的在巨噬细胞中抑制泡沫细胞形成的作用。因此,通过本发明获得的所述药物组合物或所述保健食品组合物,作为活性成分的所述槭叶蚊子草醇提取物和从其中分离出的所述溶剂提取部位,或从所述槭叶蚊子草的乙酸乙酯提取部位中完全分离出的新化合物1和2,具有优异的降低血胆固醇水平和抑制泡沫细胞形成的作用,所述泡沫细胞是由于在巨噬细胞中引入了氧化的LDL而形成的。
通过由本发明获得的所述槭叶蚊子草醇提取物和从其中分离出的所述溶剂提取部位,或从所述槭叶蚊子草的乙酸乙酯提取部位中完全分离出的新化合物1和2可以治疗、预防或缓解的疾病或障碍,具体选自由高胆固醇血症,高脂血症,动脉硬化,动脉粥样硬化,周围血管病,异常血脂症,高β脂蛋白血症,低α脂蛋白血症,高胆固醇血症,高甘油三酸酯血症,家族性高胆固醇血症,心血管障碍,冠心病,冠状动脉疾病,冠状血管病,心绞痛,局部缺血,心脏缺血,血栓症,心肌梗塞,中风,周围性血管疾病,再灌注损伤,血管成形术后再狭窄,高血压,充血性心力衰竭,糖尿病,糖尿病相关的血管并发症,肥胖症和内毒素血症组成的组。
本发明的效果不限于上述效果。应当理解,本发明的效果包括可以从本发明的说明书中推断出的所有效果。
已经参照其优选实施例详细描述了本发明。然而,本领域技术人员可以理解的是,在不脱离本发明的原理和精神的情况下,可以在这些实施例中进行各种改变。
Claims (24)
1.槭叶蚊子草(Filipendula glaberrima)提取物或其提取部位在制备用于预防、改善或治疗心血管疾病的药物中的应用。
2.槭叶蚊子草提取物或其提取部位在制备用于抗氧化的药物中的应用。
3.槭叶蚊子草提取物或其提取部位在制备用于降低血液中的胆固醇水平的药物中的应用。
4.槭叶蚊子草提取物或其提取部位在制备用于抑制泡沫细胞生成的药物中的应用。
5.根据权利要求1-4中任一项所述的应用,其中,所述槭叶蚊子草提取物是槭叶蚊子草的地上部分或地下部分的提取物。
6.根据权利要求1-4中任一项所述的应用,其中,所述提取物是通过用水,C1-C5醇类,丙酮,丙酮水溶液或C1-C5醇类水溶液提取而获得的提取物。
7.根据权利要求6所述的应用,其中,所述C1-C5醇类水溶液和所述丙酮水溶液的浓度各自独立地为10%至90%(v/v)。
8.根据权利要求1-4中任一项所述的应用,其中,所述提取部位为槭叶蚊子草C1-C5醇类提取物的乙酸乙酯提取部位。
9.根据权利要求1所述的应用,其中,所述槭叶蚊子草提取物或其提取部位通过抑制HMG-CoA还原酶活性,抑制泡沫细胞生成和抑制脂质过氧化物生成中的至少一种来预防、改善或治疗心血管疾病。
10.根据权利要求2所述的应用,其中,所述槭叶蚊子草提取物或其提取部位通过清除自由基,抑制超氧阴离子生成和抑制脂质过氧化物生成中的至少一种来表现出抗氧化作用。
11.根据权利要求1-4中任一项所述的应用,其中,所述槭叶蚊子草提取物或其提取部位以保健食品组合物的形式给药。
12.根据权利要求1所述的应用,其中,所述槭叶蚊子草提取物或其提取部位以药物组合物的形式给药。
13.根据权利要求12所述的应用,其中,所述药物组合物以注射剂,粉剂,颗粒剂,片剂,胶囊剂,混悬剂,乳剂,糖浆剂,气雾剂和外用制剂中的任何一种形式配制。
14.根据权利要求1所述的应用,其中,所述心血管疾病包含选自由高胆固醇血症,高脂血症,动脉硬化,动脉粥样硬化,周围血管病,异常血脂症,高β脂蛋白血症,低α脂蛋白血症,高胆固醇血症,高甘油三酸酯血症,家族性高胆固醇血症,心血管障碍,冠心病,冠状动脉疾病,冠状血管病,心绞痛,局部缺血,心脏缺血,血栓症,心肌梗塞,中风,周围性血管疾病,再灌注损伤,血管成形术后再狭窄,高血压,充血性心力衰竭,糖尿病,糖尿病相关的血管并发症,肥胖症和内毒素血症组成的组中的至少一种。
17.一种用于预防、改善或治疗心血管疾病的组合物,其包含根据权利要求15或16所述的化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物作为活性成分。
18.一种用于改进抗氧化作用的保健食品组合物,其包含根据权利要求15或16所述的化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物作为活性成分。
19.一种用于降低血胆固醇水平的保健食品组合物,其包含根据权利要求15或16所述的化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物作为活性成分。
20.一种用于抑制泡沫细胞形成的保健食品组合物,其包含根据权利要求15或16所述的化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物作为活性成分。
21.根据权利要求17所述的组合物,其中,所述心血管疾病包含选自由高胆固醇血症,高脂血症,动脉硬化,动脉粥样硬化,周围血管病,异常血脂症,高β脂蛋白血症,低α脂蛋白血症,高胆固醇血症,高甘油三酸酯血症,家族性高胆固醇血症,心血管障碍,冠心病,冠状动脉疾病,冠状血管病,心绞痛,局部缺血,心脏缺血,血栓症,心肌梗塞,中风,周围性血管疾病,再灌注损伤,血管成形术后再狭窄,高血压,充血性心力衰竭,糖尿病,糖尿病相关的血管并发症,肥胖症和内毒素血症组成的组中的至少一种。
22.根据权利要求17所述的组合物,其中,所述组合物是一种药物组合物。
23.根据权利要求17所述的组合物,其中,所述组合物是一种保健食品组合物。
24.根据权利要求15或16所述的化合物,其旋光异构体,其药学上可接受的盐,其水合物或其溶剂化物,其中,式1的所述化合物或式2的所述化合物是从槭叶蚊子草中分离出的成分。
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09291038A (ja) * | 1995-12-12 | 1997-11-11 | Ennagram Sarl | 局部的皮下脂肪過多の症候局部処置用をはじめとする、植物抽出物の混合物とその使用 |
US20040132816A1 (en) * | 2003-01-06 | 2004-07-08 | Liao Medical Corporation | Lipid metabolism and fructus crataegus |
FR2979824A1 (fr) * | 2011-09-13 | 2013-03-15 | Vetinnov | Composition a usage humain ou veterinaire. |
WO2013060715A1 (de) * | 2011-10-28 | 2013-05-02 | Dr. Willmar Schwabe Gmbh & Co. Kg | Verwendung von extrakten aus filipendula zur prophylaxe und behandlung von extrapyramidal-motorischen störungen |
US20150133552A1 (en) * | 2012-05-16 | 2015-05-14 | Joachim Hans | Polyhydroxylated pentacyclic triterpene acids as hmg-coa reductase inhibitors |
CN104768562A (zh) * | 2011-10-28 | 2015-07-08 | 威玛舒培博士两合公司 | 来自蚊子草的提取物用于治疗和预防慢性疼痛的用途 |
CN106065023A (zh) * | 2015-04-23 | 2016-11-02 | 中国医学科学院药物研究所 | 可水解鞣质类化合物、其药物组合物及其用途 |
JP2017036243A (ja) * | 2015-08-11 | 2017-02-16 | キューサイ株式会社 | ジペプチジルペプチダーゼ−4阻害剤 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6297273B1 (en) * | 1996-04-02 | 2001-10-02 | Mars, Inc. | Use of cocoa solids having high cocoa polyphenol content in tabletting compositions and capsule filling compositions |
JP3766018B2 (ja) * | 2001-12-17 | 2006-04-12 | 一丸ファルコス株式会社 | 活性酸素消去剤 |
KR20100124519A (ko) * | 2009-05-19 | 2010-11-29 | (주)아모레퍼시픽 | 녹차 추출물을 함유하는 조성물 |
KR20110122451A (ko) * | 2010-05-04 | 2011-11-10 | 주식회사 코리아나화장품 | 흰진범 추출물을 유효성분으로 함유하는 화장료 조성물 |
KR20110122448A (ko) * | 2010-05-04 | 2011-11-10 | 주식회사 코리아나화장품 | 지리터리풀 추출물을 유효성분으로 함유하는 화장료 조성물 |
KR101523820B1 (ko) | 2012-10-08 | 2015-05-28 | 상지대학교산학협력단 | 섬쑥부쟁이 추출물을 유효성분으로 함유하는 비만 또는 대사성질환의 예방 또는 치료용 약학적 조성물 |
KR101516764B1 (ko) | 2013-07-19 | 2015-05-04 | 한국생명공학연구원 | 환삼덩굴 추출물을 포함하는 간질환 또는 동맥경화의 예방 또는 치료용 조성물 |
ITRM20130502A1 (it) | 2013-09-11 | 2015-03-12 | Aboca Spa Societa Agricola | Estratto di filipendula vulgaris e suoi usi |
KR101547758B1 (ko) * | 2014-03-05 | 2015-08-26 | 주식회사 크라운진 | 탈모 예방 및 양모, 육모 촉진용 조성물 |
KR20160001805A (ko) | 2014-06-26 | 2016-01-07 | 한국식품연구원 | 석류풀 추출물, 질경이택사 추출물, 담팥수 추출물 또는 개승마 추출물을 포함하는 Th2-매개 면역 질환의 예방, 개선 또는 치료용 조성물 |
KR20160018051A (ko) | 2014-08-07 | 2016-02-17 | (주)바이오토피아 | 장뇌삼 발효 추출물을 포함하는 항고지혈증 및 항동맥경화 조성물 |
KR20160084990A (ko) | 2015-01-07 | 2016-07-15 | 구을리주식회사 | 아까시나무 추출물을 함유하는 동맥경화증, 심근경색, 뇌졸중, 혈관성치매, 간질환, 이상지질혈증 또는 혈전증 예방 또는 치료용 조성물 |
KR20170091306A (ko) | 2016-02-01 | 2017-08-09 | 주식회사 더삼점영 | Gelatinase의 방해제를 터리풀 추출물에서 탐색하여 얻은 주름억제용 화장료 조성물 |
KR101938055B1 (ko) | 2017-04-05 | 2019-01-14 | 성균관대학교산학협력단 | 개꼬시래기 추출물 또는 분획물을 유효성분으로 함유하는 동맥경화증의 예방 및 치료용 약학 조성물 |
KR102444911B1 (ko) * | 2019-07-12 | 2022-09-21 | 코스맥스바이오 주식회사 | 산나물 추출물을 유효성분으로 하는 근육관련 질환 예방 또는 치료, 근기능 개선 또는 운동수행능력 개선용 조성물 |
-
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-
2020
- 2020-09-17 US US17/023,447 patent/US11638737B2/en active Active
- 2020-10-09 CN CN202011074636.2A patent/CN112641095A/zh active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09291038A (ja) * | 1995-12-12 | 1997-11-11 | Ennagram Sarl | 局部的皮下脂肪過多の症候局部処置用をはじめとする、植物抽出物の混合物とその使用 |
US20040132816A1 (en) * | 2003-01-06 | 2004-07-08 | Liao Medical Corporation | Lipid metabolism and fructus crataegus |
FR2979824A1 (fr) * | 2011-09-13 | 2013-03-15 | Vetinnov | Composition a usage humain ou veterinaire. |
WO2013060715A1 (de) * | 2011-10-28 | 2013-05-02 | Dr. Willmar Schwabe Gmbh & Co. Kg | Verwendung von extrakten aus filipendula zur prophylaxe und behandlung von extrapyramidal-motorischen störungen |
CN104768562A (zh) * | 2011-10-28 | 2015-07-08 | 威玛舒培博士两合公司 | 来自蚊子草的提取物用于治疗和预防慢性疼痛的用途 |
US20150133552A1 (en) * | 2012-05-16 | 2015-05-14 | Joachim Hans | Polyhydroxylated pentacyclic triterpene acids as hmg-coa reductase inhibitors |
CN106065023A (zh) * | 2015-04-23 | 2016-11-02 | 中国医学科学院药物研究所 | 可水解鞣质类化合物、其药物组合物及其用途 |
JP2017036243A (ja) * | 2015-08-11 | 2017-02-16 | キューサイ株式会社 | ジペプチジルペプチダーゼ−4阻害剤 |
Non-Patent Citations (13)
Title |
---|
TAKASHI YOSHIDA 等: "Ellagitannin Monomers and Oligomers from Euphorbia prostrata AIT. And Oligomers from Loropetalum chinense OLIV.", 《CHEM.PHARM.BULL》, vol. 38, no. 12, pages 3296 * |
卫强: "《植物茎叶化学成分的提取分离及活性研究》", 30 September 2018, 合肥:安徽大学出版社, pages: 67 - 68 * |
吴玲芳 等: "可水解鞣质单体化学与药理作用研究进展", 《中草药》, vol. 45, no. 2, pages 290 * |
张学伟: "《蔬果汁养生大全》", 31 July 2015, 北京:中医古籍出版社, pages: 51 * |
曲晓宇: "槭叶蚊子草中黄酮类成分的研究", 《中国优秀硕士学位论文全文数据库(电子期刊)》 * |
曲晓宇: "槭叶蚊子草中黄酮类成分的研究", 《中国优秀硕士学位论文全文数据库(电子期刊)》, no. 09, 15 September 2010 (2010-09-15), pages 10 * |
杨琳: "槲皮苷药理活性研究进展", 《亚太传统医药》 * |
杨琳: "槲皮苷药理活性研究进展", 《亚太传统医药》, vol. 11, no. 6, 24 March 2015 (2015-03-24), pages 61 * |
王忠良: "《降血压降血脂吃什么宜忌速查》", 31 March 2013, 北京:中国轻工业出版社, pages: 163 * |
苗成 等: "槲皮素对ox-LDL 所致的小鼠巨噬细胞脂质蓄积和过氧化的影响", 《中国病理生理杂质》 * |
苗成 等: "槲皮素对ox-LDL 所致的小鼠巨噬细胞脂质蓄积和过氧化的影响", 《中国病理生理杂质》, vol. 29, no. 8, 15 August 2013 (2013-08-15) * |
黄文文: "山楂中抑制HMG-COA还原酶的活性成分研究及其安全性评价", 《中国中药杂志》 * |
黄文文: "山楂中抑制HMG-COA还原酶的活性成分研究及其安全性评价", 《中国中药杂志》, vol. 35, no. 18, 15 September 2010 (2010-09-15), pages 2428 * |
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