CN1819826A - 血管活性剂的组合、它们在药学和化妆品领域中的用途和含有它们的制剂 - Google Patents

血管活性剂的组合、它们在药学和化妆品领域中的用途和含有它们的制剂 Download PDF

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CN1819826A
CN1819826A CNA2004800197457A CN200480019745A CN1819826A CN 1819826 A CN1819826 A CN 1819826A CN A2004800197457 A CNA2004800197457 A CN A2004800197457A CN 200480019745 A CN200480019745 A CN 200480019745A CN 1819826 A CN1819826 A CN 1819826A
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E·邦巴尔代利
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Abstract

本发明涉及在静脉或动脉水平发挥作用的血管活性物质与包括磷酸二酯酶V在内的磷酸二酯酶抑制剂的组合，尤其是：维司那定或七叶灵；至少一种选自以下的化合物：淫羊藿苷或其衍生物或含有它的提取物、游离形式的或与磷脂复合的银杏(Gingko biloba)二聚黄酮、阿曼托黄素；至少一种选自以下的化合物：七叶素、与磷脂复合的七叶素β－谷甾醇、绢毛苷、与磷脂复合的绢毛苷或者游离形式的或与磷脂复合的积雪草(Centella asiatica)提取物。本发明的制剂可用于减轻脂膜病和与下肢静脉功能不全有关的问题。

Description

血管活性剂的组合、它们在药学和化妆品领域中的用途和含有它们的制剂
发明领域
本发明涉及在静脉或动脉水平发挥作用的血管活性物质与包括cGMP磷酸二酯酶V在内的磷酸二酯酶抑制剂的组合。
发明背景
维司那定是一种主要在阿密茴香(Ammi visnaga)种子中发现的香豆素，阿密茴香是一种常规用于治疗绞痛样病症的植物。该化合物已被作为冠脉扩张剂应用于药学领域。
还已经证明当局部应用时该化合物对毛细血管前动脉和微动脉具有强血管动力学(vasokinetic)作用，并且可增加血流和组织灌注(EP 0418806)。血液向组织的供应带来了较好的营养并使代谢废物被消除，从而对治疗区域有益。维司那定还具有抗磷酸二酯酶的活性。
七叶灵(esculoside)是一种存在于许多植物例如欧洲七叶树(Aesculushippocastanum)、Fraxinus communis等中的香豆素葡萄糖苷，其在静脉和动脉水平上均具有血管动力学作用和静脉取向性(venotropic)活性。
对cGMP磷酸二酯酶V具有活性的淫羊藿苷(icarin)和其衍生物在某些领域中是有效的微循环活化剂。
阿曼托黄素是一种双黄酮，其以不多的量存在于多种植物例如银杏(Gingkobiloba)、Brakeringea zanguebarica和红豆杉(Taxus sp)中。
七叶树或积雪草(Centella asiatica)的皂草苷作用于静脉和淋巴系统，在其中它们发挥抗水肿作用，该作用有助于淋巴排出(lymph drainage)。
发明内容
本发明涉及药物、饮食、化妆品或营养组合物，其包含：
-维司那定或七叶灵；
-至少一种选自以下的化合物：淫羊藿苷或其衍生物或含有它的提取物、游离形式的或与磷脂复合的银杏二聚黄酮和阿曼托黄素；
-至少一种选自以下的化合物：七叶素、与磷脂复合的七叶素β-谷甾醇、绢毛苷(sericoside)、与磷脂复合的绢毛苷或者游离形式的或与磷脂复合的积雪草提取物。
本发明的血管活性物质的组合可同时在动脉和静脉水平发挥作用并且可作用于淋巴排出，其可减轻淤滞水肿，淤滞水肿是慢性静脉功能不全的首要症状之一，伴有从蜂窝织炎至各种病原学的脚样结构溃疡(crural ulcer)的病理学结果。下肢循环不足的警告性体征包括低于正常值的皮肤温度、腿部沉重感和伴有外周疼痛的肢端缺氧综合征。已经进行了各种努力来治疗这些症状，但均不太成功。
现在已经惊奇地发现，本发明的包含具有不同作用机制的化合物的制剂可预防外周血管和组织变性。
最常见的例子是蜂窝织炎或变性脂膜病(degenerative panniculopathy)。在形成疼痛的纤维性结节或由于脂肪细胞变性而导致脂肪沉积之前，蜂窝织炎是由于静脉功能不全而使体液和蛋白质渗入血管周隙引起的。由于机械压力而导致的水肿降低了动脉血流的自由循环。在这些环境下，脂肪细胞蓄积脂肪、变大并占用其它细胞的空间。如果要获得最大成功，这时应该开始用抗蜂窝织炎的制剂治疗。为了防止其发展成外周损伤，本发明的联合物使得该病症能够在病理前阶段被治疗。甚至当病症已经变为慢性的时，该制剂也能被成功用于消除疼痛感和降低长期治疗伴有的不希望的脂肪块，其是通过组织中环核苷酸的持续存在而诱发的脂肪酶刺激来实现的。
根据本发明，可被用作淫羊藿苷替代物的淫羊藿苷衍生物包括7-羟乙基-淫羊藿苷、7-乙氨基-淫羊藿苷、7-氨基乙基-淫羊藿苷、7-羟乙基-3-0-鼠李糖基-淫羊藿苷、7-氨基乙基-3-鼠李糖基-淫羊藿苷、8-二氢-淫羊藿苷和其在7位和3位的葡萄糖苷以及7-羟乙基-7-去葡萄糖-淫羊藿苷。
本发明的组合物优选含有维司那定。
本发明的组合物通常具有以下以重量表示的浓度范围：
-维司那定或七叶灵：0.05-2％；
-阿曼托黄素或者游离形式的或与磷脂复合的银杏二聚物：0.1-1％；
-淫羊藿苷或其衍生物或含有它的提取物：0.1-1％；
-至少一种选自以下的化合物：七叶素、与磷脂复合的七叶素β-谷甾醇、绢毛苷、与磷脂复合的绢毛苷或者游离形式的或与磷脂复合的积雪草提取物：0.5％-2％。
这些化合物可被加至最常见的药物和化妆品制剂中，例如水包油型和油包水型乳剂，其是用赋形剂、表面活性剂和增溶剂而适当实现的。
此外，可将产品配制成用于大面积皮肤治疗的乳膏剂、乳液(milk)和凝胶形式。
以下实施例详细地阐述了本发明。
实施例1-凝胶制剂
维司那定                        0.25g
7-羟乙基-7-去葡萄糖-淫羊藿苷    0.35g
阿曼托黄素                      0.25g
七叶素                          1.00g
卵磷脂                          20.00g
胆固醇                          0.50g
乙醇                            8.00g
丁基羟基甲苯                    0.01g
咪唑啉脲                        0.30g
羟丙基-甲基纤维素               2.00g
水                              适量加至100g
实施例2-凝胶制剂
七叶灵                          1.00g
淫羊藿苷                        0.35g
阿曼托黄素                        0.25g
七叶素                            1.00g
卵磷脂                            20.00g
胆固醇                            0.50g
乙醇                              8.00g
丁基羟基甲苯                      0.01g
咪唑啉脲                          0.30g
羟丙基-甲基纤维素                 2.00g
水                                适量加至100g
实施例3-凝胶制剂
维司那定                          0.25g
7-羟乙基-7-去葡萄糖-淫羊藿苷      0.35g
与磷脂复合的银杏二聚物            0.25g
与磷脂复合的七叶素β-谷甾醇       1.00g
卵磷脂                            20.00g
胆固醇                            0.50g
乙醇                              8.00g
丁基羟基甲苯                      0.01g
咪唑啉脲                          0.30g
羟丙基-甲基纤维素                 2.00g
水                                适量加至100g
实施例4-凝胶制剂
七叶灵                            0.25g
7-羟乙基-7-去葡萄糖-淫羊藿苷      0.35g
阿曼托黄素                        0.25g
绢毛苷                            1.00g
卵磷脂                    20.00g
胆固醇                    0.50g
乙醇                      8.00g
丁基羟基甲苯              0.01g
咪唑啉脲                  0.30g
羟丙基-甲基纤维素         2.00g
水                        适量加至100g
实施例5-凝胶制剂
维司那定                  0.3g
阿曼托黄素                0.4g
积雪草提取物              1.0g
卵磷脂                    20.00g
胆固醇                    0.50g
乙醇                      8.00g
丁基羟基甲苯              0.01g
咪唑啉脲                  0.30g
羟丙基-甲基纤维素         2.00g
水                        适量加至100g

Claims (11)

1.药物组合物、化妆品组合物、饮食组合物或营养组合物，其包含：
-维司那定或七叶灵；
-至少一种选自以下的化合物：淫羊藿苷或其衍生物或含有它的提取物、游离形式的或与磷脂复合的银杏(Gingko biloba)二聚黄酮、阿曼托黄素；
-至少一种选自以下的化合物：七叶素、与磷脂复合的七叶素β-谷甾醇、绢毛苷、与磷脂复合的绢毛苷或者游离形式的或与磷脂复合的积雪草(Centella asiatica)提取物。
2.权利要求1中所述的组合物，其具有以下以重量表示的浓度范围：
-维司那定或七叶灵：0.05-2％；
-阿曼托黄素或者游离形式的或与磷脂复合的银杏二聚黄酮：0.1-1％；
-淫羊藿苷或其衍生物或含有它的提取物：0.1-1％；
-七叶素、与磷脂复合的七叶素β-谷甾醇、绢毛苷、与磷脂复合的绢毛苷或者游离形式的或与磷脂复合的积雪草提取物：0.5％-2％。
3.权利要求1或2中所述的组合物，其中淫羊藿苷衍生物包括7-羟乙基-淫羊藿苷、7-乙氨基-淫羊藿苷、7-氨基乙基-淫羊藿苷、7-羟乙基-3-0-鼠李糖基-淫羊藿苷、7-氨基乙基-3-鼠李糖基-淫羊藿苷、8-二氢-淫羊藿苷和其在7位和3位的葡萄糖苷以及7-羟乙基-7-去葡萄糖-淫羊藿苷。
4.权利要求1-3中任意一项所述的组合物，其是乳膏剂、凝胶剂、洗剂、乳液的形式。
5.权利要求1中所述的组合物，其含有维司那定。
6.权利要求1中所述的组合物，其含有维司那定、7-羟乙基-7-去葡萄糖-淫羊藿苷、阿曼托黄素和七叶素。
7.权利要求1中所述的组合物，其含有七叶灵、淫羊藿苷、阿曼托黄素、七叶素。
8.权利要求1中所述的组合物，其含有维司那定、7-羟乙基-7-去葡萄糖-淫羊藿苷、游离形式的或与磷脂复合的银杏二聚物。
9.权利要求1中所述的组合物，其含有维司那定、与磷脂复合的银杏二聚物、与磷脂复合的七叶素β-谷甾醇。
10.权利要求1中所述的组合物，其含有七叶灵、与磷脂复合的银杏二聚物、与磷脂复合的七叶素β-谷甾醇。
11.以下物质的组合在制备组合物中的用途：
-维司那定或七叶灵；
-至少一种选自以下的化合物：淫羊藿苷或其衍生物或含有它的提取物、游离形式的或与磷脂复合的银杏二聚黄酮、阿曼托黄素；
-至少一种选自以下的化合物：七叶素、与磷脂复合的七叶素β-谷甾醇、绢毛苷、与磷脂复合的绢毛苷或者游离形式的或与磷脂复合的积雪草提取物，
所述组合物用于治疗脂膜病和与下肢静脉功能不全有关的问题。
CNA2004800197457A 2003-07-11 2004-07-06 血管活性剂的组合、它们在药学和化妆品领域中的用途和含有它们的制剂 Pending CN1819826A (zh)

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