CN1812729A - 血管保护剂的组合以及含有它们的制剂 - Google Patents

血管保护剂的组合以及含有它们的制剂 Download PDF

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CN1812729A
CN1812729A CNA2004800177716A CN200480017771A CN1812729A CN 1812729 A CN1812729 A CN 1812729A CN A2004800177716 A CNA2004800177716 A CN A2004800177716A CN 200480017771 A CN200480017771 A CN 200480017771A CN 1812729 A CN1812729 A CN 1812729A
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E·邦巴尔代利
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Abstract

用于预防和治疗由血浆脂质过剩引起的血管损伤的血管保护剂的组合,包含聚二十级醇、生育三烯酚和/或番茄红素、procyanidole低聚物以及富含ω-3,ω-6不饱和脂肪酸的植物油。

Description

血管保护剂的组合以及含有它们的制剂
发明领域
本发明涉及用于预防和治疗由血浆脂质过量引起的血管损伤的血管保护剂的组合。
本发明的组合降低血中胆固醇和甘油三酯水平,同时保护血管壁免受由自由基和氧化型胆固醇超量产生引起的损伤,从而加固血管壁。
发明内容
本发明涉及血管保护剂的组合以及含有所述组合的药物组合物。
动脉硬化性疾病是一种不仅与脂质状况相关联的非常复杂的现象,因此,任何与血管保护和降低自由基超量产生有关的协同作用都具有很大的治疗价值。慢性变性疾病例如心血管病并非只有一个单一来源。高甘油三酯和胆固醇水平,伴以脂蛋白组分的比例改变以及高血压,毋庸置疑会引起预后不好的显著的血管损伤。因此需要降低血中胆固醇和甘油三酯水平,同时加固和保护动脉壁。
现在已经发现:组合具有不同作用机制的血管保护剂可有利地达到此目的。
具体而言,本发明涉及保护下述组分的药物、饮食或营养组合物:
-一种或多种聚二十级醇及其酯,为纯品或萃取物;
-生育三烯酚和/或番茄红素,优选生育三烯酚;
-任选与磷脂复合的一种或多种procyanidole低聚物;
-富含ω-3,ω-6不饱和脂肪酸的植物油。
该组合中各单一组分的降低血胆固醇或更通常的抗动脉粥样硬化的活性是已知的,但是只有通过它们的组合使用才可以获得特别显著的预防或治疗效果。
作为抗动脉粥样硬化药的与磷脂复合的procyanidole低聚物的用途和制备在WO 99/29331中有公开。
聚二十级醇以及ω-3,ω-6不饱和脂肪酸曾经有段时间成为心脏病学和心血管领域的研究对象(分别参见Iht J Clin Pharm Res 1994;14:27-33和Ann.Intern.Med.1999;130:554-62),而属于类胡萝卜素家族的生育三烯酚和番茄红素曾经作为能够预防脂质过氧化及自由基形成的药物以及还作为化学预防药物进行了深入的研究(Clin.Biochem 1999;32:309-19)。
根据本发明所用的聚二十级醇是直链的长链脂肪醇,通常是具有24至30个碳原子的直链醇,可通过对例如橄榄、小麦、稻、甘蔗及其它来源的植物材料中的蜡质进行皂化而获得。这些化合物可以以游离形式使用,或者以被阿魏酸或其它多种在苯基部分被取代的肉桂酸(例如对硝基、对羟基及间氯肉桂酸)酯化的形式使用。
用于本发明用途的procyanidole低聚物可以从葡萄(Vitis vinifera)、大叶茶(Camellia sinensis)、欧洲七叶树(Aesculus hippocastanum)、油橄榄(Oleaeuropea)中获得。
植物油优选选自月见草(Enothera biennis)油、黑茶藨子(Ribes nigrum)油或马齿苋(Portulaca oleracea)油,更优选月见草油。存在于所述油中的ω-3,ω-6不饱和脂肪酸可以任选通过酯交换反应被转化为相应的烷基酯,特别是相应的乙基酯,例如通过用醇和硫酸在苯(以共沸除去水)存在下处理这种油。
本发明的组合物还可包含四羟黄酮本身或其7,3′,4′-羟乙基衍生物的形式。
本发明的制剂每单位剂型可以包含5至30毫克(优选15毫克)的聚二十级醇、1至50毫克(优选8毫克)的生育三烯酚或番茄红素、30至200毫克的原花色素或100至320毫克与磷脂复合的原花色素以及150至300毫克的植物油。
20名患有伴有颈动脉斑块的原发性高血脂患者采用本发明的制剂治疗,该制剂具有下列组合:
稻聚二十级醇(70%聚二十级醇)          15mg
生育三烯酚                            14mg
Procyanidole低聚物/磷脂                   320mg
月见草油                            适量至500mg
每日2粒胶囊治疗两个月后,患者显示出如EcoDoppler所证实的正常化脂质参数及改善的斑块状况。
以下实施例更加详细地阐述本发明:
实施例I
来自稻或橄榄残余油的聚二十级醇            15mg
生育三烯酚                                14mg
Procyanidole低聚物/磷脂                   320mg
月见草油                            适量至500mg
实施例II
来自橄榄残余油的经阿魏酸酯化
的聚二十级醇                              30mg
生育三烯酚                                14mg
Procyanidole低聚物/磷脂                   250mg
月见草油适量至                            500mg
实施例III
阿魏酸二十八烷基酯                        12mg
生育三烯酚                                12mg
没食子酸儿茶精没食子酸盐/磷脂酰胆碱1∶1   250mg
二十碳五烯酸乙酯                    适量至500mg
实施例IV
来自稻或橄榄残余油的经阿魏酸酯化
的聚二十级醇                              15mg
生育三烯酚                                14mg
Procyanidole低聚物/磷脂                   250mg
月见草油                            适量至500mg
实施例V
来自稻或橄榄残余油的聚二十级醇            15mg
生育三烯酚                       14mg
Procyanidole低聚物               150mg
月见草油                   适量至500mg

Claims (8)

1.药物、饮食或营养组合物,包含:
-一种或多种聚二十级醇或其酯,为纯品或萃取物;
-生育三烯酚和/或番茄红素,优选生育三烯酚;
-任选与磷脂复合的一种或多种procyanidole低聚物;
-富含ω-3,ω-6不饱和脂肪酸的植物油。
2.如权利要求1所要求的组合物,其中的植物油选自月见草油、黑茶藨子油或马齿苋油。
3.如权利要求2所要求的组合物,其中的植物油是月见草油。
4.如权利要求1-3中任一项所要求的组合物,还包含四羟黄酮本身或其7,3′,4′-羟乙基衍生物的形式。
5.如权利要求1-4中任一项所要求的组合物,其中的聚二十级醇被阿魏酸或其它多种被取代的肉桂酸酯化。
6.如权利要求1-5中任一项所要求的组合物,其中的procyanidole低聚物来自葡萄、大叶茶、欧洲七叶树、油橄榄。
7.如权利要求1-6中任一项所要求的组合物,每单位剂型包含5至30毫克聚二十级醇、1至50毫克的生育三烯酚或番茄红素、100至320毫克与磷脂复合的原花色素、150至300毫克植物油。
8.下述组分的组合在制备降低血胆固醇和/或抗动脉粥样硬化的药物、饮食或营养组合物中的用途:
-一种或多种游离或酯化形式的聚二十级醇,为纯品或包含它们的萃取物;
-生育三烯酚和/或番茄红素,优选生育三烯酚;
-任选与磷脂复合的一种或多种procyanidole低聚物;
-富含ω-3,ω-6不饱和脂肪酸的植物油。
CNB2004800177716A 2003-06-27 2004-06-17 血管保护剂的组合以及含有它们的制剂 Expired - Fee Related CN100475061C (zh)

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JP4960087B2 (ja) 2012-06-27
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