CN103705402A - 包含4-取代的间苯二酚和高碳链酯的低油组合物 - Google Patents

包含4-取代的间苯二酚和高碳链酯的低油组合物 Download PDF

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CN103705402A
CN103705402A CN201310438957.XA CN201310438957A CN103705402A CN 103705402 A CN103705402 A CN 103705402A CN 201310438957 A CN201310438957 A CN 201310438957A CN 103705402 A CN103705402 A CN 103705402A
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M·D·德福特
S·考尔
M·D·索斯霍
闻萍
J·M·吴
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Abstract

本发明提供了一种组合物,其包含水、约0.1%至约0.4%的4-取代的间苯二酚、具有至少约25个碳原子的酯和聚合乳化剂。所述组合物包含按重量计小于约5%的油并且基本上不含单体乳化剂。本发明还提供了处理皮肤的方法。

Description

包含4-取代的间苯二酚和高碳链酯的低油组合物
技术领域
本发明提供了包含4-取代的间苯二酚、高碳链酯和美容上可接受的局部用载体的低油组合物。所述组合物用于向皮肤局部施用。
背景技术
已知4-取代的间苯二酚当局部施用时会给皮肤提供抗老化和增亮益处。由于多种原因(诸如成本和制剂完整性),合乎需要的是,降低4-取代的间苯二酚在局部用的皮肤产品中的浓度。然而,降低4-取代的间苯二酚的浓度还可以减少观察到的益处。因此,发明人已经认识到对具有降低的4-取代的间苯二酚浓度的制剂的需求。令人惊奇地,发明人已经发现,包括高碳链酯的低油组合物可以用低浓度的4-取代的间苯二酚配制,且仍然提供皮肤益处。
发明内容
在一个方面,本发明提供了一种组合物,其包含水、约0.1%至约0.4%的4-取代的间苯二酚、具有至少约25个碳原子的酯和聚合乳化剂。所述组合物包含按重量计小于约5%的油并且基本上不含单体乳化剂。从本发明的详细描述和从权利要求书会明白本发明的其它特征和优点。
具体实施方式
据信,本领域技术人员基于本文中的描述可以在最完全程度上使用本发明。下述的具体实施例应当解释为仅仅是示例性的,无论如何不以任何方式限制本公开内容的其它部分。
除非另外定义,本文使用的所有技术和科学术语具有本发明所属领域的普通技术人员所通常理解的相同含义。除非另有说明,百分比或浓度表示按重量计的百分比或浓度(即,%(W/W))。除非另外说明,所有范围包括端点,例如,“4-9”包括端点4和9。
本文中使用的“局部施用”是指直接地涂或铺在外层皮肤、头皮或毛发上,例如,通过使用手或涂布器诸如拭子、辊子或喷雾器。
本文中使用的“美容上可接受的”是指该术语描述的成分适合用于接触组织(例如,皮肤或毛发),而没有不适当的毒性、不相容性、不稳定性、刺激、过敏反应等。
本发明的组合物适合用于处理皮肤老化征象。本文中使用的“皮肤老化征象”包括纹线和皱纹的存在、弹性缺失、肤色不均和斑点(blotchiness)。在一个特别优选的实施例中,老化征象是纹线和皱纹的存在和/或弹性缺失。
本文中使用的“处理皮肤老化征象”表示减轻、减少、预防、改善、或消除上述的皮肤老化的存在或征象。
本文中使用的“皱纹”包括细纹线、细皱纹或粗皱纹。皱纹的例子包括但不限于眼睛周围的细纹线(例如“鱼尾纹”)、前额和面颊皱纹、眉心纹和嘴巴周围的笑纹。
本文中使用的“弹性缺失”包括皮肤或组织的弹性或结构完整性的缺失,包括但不限于松垂、松弛和松散的组织。弹性或组织结构完整性的缺失可以是许多因素的结果,所述因素包括但不限于疾病、老化、激素变化、机械创伤、环境损害,或者是向组织施用诸如化妆品或药物之类的产品的结果。
本文中使用的“肤色不均”是指与弥漫状或斑驳状色素沉着有关的皮肤状况,所述色素沉着可分类为色素沉着过度,诸如炎症后的色素沉着过度。
本文中使用的“斑点”是指与发红或红斑相关的皮肤状况。
本发明的组合物适合用于治疗痤疮。本文中使用的“治疗痤疮”表示减轻、减少、预防、改善、或消除由激素和其它物质对皮脂腺和毛囊的作用引起的障碍的存在或征象,通常导致毛孔的堵塞和病损在皮肤上的形成。
本文中使用的“化妆品”表示保持、恢复、赋予、模拟或增强身体美丽外观或者似乎会增进美貌或年轻的美容物质或制品,特别是涉及组织或皮肤的外观时。
本文中使用的术语“增亮皮肤”通常指使皮肤色调、皮肤颜色和/或皮肤色度淡化、变亮、变白和/或均匀化,和/或指灰黄度降低,和/或指色素沉着过度的斑痕和/或病损(包括但不限于色素斑、黑色素斑、老年斑、日晒斑、衰老性着色班、雀斑、单纯性雀斑痣、色素性日光性角化病、脂溢性角化病、黑斑病、痤疮斑痕、炎症后色素沉着过度、着色斑、雀斑(ephelides)、它们中两种或更多种的组合等等)的淡化和/或褪色。在某些实施例中,“增亮皮肤”还指增加的皮肤光亮度、光泽度、半透明度和/或发光和/或获得更光亮、光泽、半透明的或发光的肤色外观或较低的黄色或萎黄色肤色。在某些优选的实施例中,“增亮皮肤”指使皮肤色调增亮和均匀,增加皮肤光亮度和/或淡化老年斑。
本文中使用的术语“需要进行皮肤增亮处理的皮肤”一般指表现出一种或多种选自如下特性的皮肤:具有低于41的个体类型角(IndividualTypology Angle,ITA)测量值(根据2007年公布的COLIPAGUIDELINE:GUIDELINE FOR THE COLORIMETRIC DETERMINATIONOF SKIN COLOUR TYPING AND PREDICTION OF THE MINIMALERYTHEMAL DOSE(MED)WITHOUT UV EXPOSURE测定,将该文献通过引用并入本文,并且其在下文中进一步描述)的皮肤,发暗和/或萎黄的皮肤,包括UV暗化的皮肤,具有不均匀色调的皮肤,或具有一处或多处色素沉着过度的斑痕和/或病损(包括但不限于色素斑、黑色素斑、老年斑、日晒斑、衰老性着色班、雀斑、单纯性雀斑痣、色素性日光性角化病、脂溢性角化病、黑斑病、痤疮斑痕、炎症后色素沉着过度、着色斑、雀斑、它们中两种或更多种的组合等等)的皮肤。在COLIPA指南中,皮肤颜色根据ITA值定义为:非常浅色的皮肤>55,浅色皮肤41-55,中等色皮肤28-41,棕褐色皮肤<28。在某些优选的实施例中,“需要进行皮肤增亮的皮肤”指皮肤的ITA值低于41,例如约40或更低,约35或更低,约30或更低,或更优选约28或更低的个体。在某些优选的实施例中,本发明涉及用于选自萎黄和/或暗化皮肤的需要进行皮肤增亮处理的皮肤上的组合物和方法。在某些其他优选的实施例中,本发明涉及用于需要进行选自老年斑、雀斑、痤疮后留下的斑痕以及它们中两种或更多种的组合的皮肤增亮处理的组合物和方法。
4-取代的间苯二酚
本发明的组合物包含4-取代的间苯二酚。4-取代的间苯二酚具有间苯二酚的化学结构,但是包括在4位处的取代。合适的4-取代的间苯二酚包括具有烷基、芳基、烯基或炔基取代的那些间苯二酚。在一个实施例中,所述4-取代的间苯二酚包含C4-C10取代。在某些实施例中,其它位置可以是被取代的或未被取代的。
在一个实施例中,所述4-取代的间苯二酚是4-己基间苯二酚,其具有下述结构:
Figure BDA0000386745560000041
4-己基间苯二酚是商购可得的,例如,作为“SYNOVEA HR”从Sytheon of Lincoln Park,NJ得到。
发明人已经发现,根据本发明的包含低水平的4-取代的间苯二酚的局部用组合物会提供令人惊讶地好的皮肤益处(诸如抗老化、抗痤疮和增亮益处)的效力。具体地,所述组合物包含按重量计约0.1%至约0.4%的4-取代的间苯二酚。在某些实施例中,所述组合物包含按重量计约0.2%至约0.4%(诸如约0.3%至约0.4%)的4-取代的间苯二酚。可以使用一种或超过一种4-取代的间苯二酚。
高碳链酯
本发明的组合物包含高碳链酯,即,具有至少约25个碳原子的酯。发明人已经发现,在所述组合物中包含的高碳链酯倾向于显著提高4-取代的间苯二酚的活性。合适的高碳链酯通常是疏水的,且包括具有例如25至约100个碳原子的那些,诸如具有25至约75个碳原子的那些,诸如具有25至约50个碳原子的那些,诸如具有25至37个碳原子的那些。可以使用一种或超过一种高碳链酯。
在一个实施例中,所述高碳链酯是支化的。
在另一个实施例中,所述高碳链酯在室温和常压下为液体,且可以具有小于30℃(诸如小于25℃)的熔点。
在另一个实施例中,所述高碳链酯具有1-4个酯基。
所述高碳链酯理想地是非离子的,且不含否则倾向于使所述酯为两亲的亲水部分(例如,阴离子的、阳离子的、两性离子的或非离子的极性基团,包括硫酸根、磺酸根、羧酸根、磷酸根、膦酸根、铵(包括单-、二-和三-烷基铵物质)、吡啶
Figure BDA0000386745560000051
、咪唑啉
Figure BDA0000386745560000052
、脒
Figure BDA0000386745560000053
、聚(亚乙基铵)、铵基烷基磺酸根、铵基烷基羧酸根、两性乙酸根、羟基和聚(亚乙基氧基)磺酰基)。
此外,所述高碳链酯理想地仅由氢、碳和氧原子组成,且可以不含醚官能团。
合适的高碳链酯的具体例子包括:辛基十二醇新戊酸酯,即可作为ELEFAC I-205从Alzo International Inc.of Sayerville,New Jersey商购得到的C25酯;和季戊四醇四乙基己酸酯,即可作为DUB PTO也从AlzoInternational Inc.of Sayerville,New Jersey商购得到的C37酯。
所述组合物中的高碳链酯的量可以在例如按所述组合物重量计约0.1%至约5%的范围内。在某些实施例中,所述高碳链酯以按所述组合物重量计约0.1%至约3%(诸如约1%至约3%)的量存在。
聚合乳化剂
本发明的组合物包含聚合乳化剂(即,具有一个或多个可定义的重复单元)。在某些实施例中,所述重复单元不是氧基亚烷基(-CnO-),其中n是1-5。所述聚合乳化剂适合用于乳化在连续水相中的不连续油相微滴,或反之亦然。具体地,当将按重量计0.25%-2%的聚合乳化剂与按重量计1%的矿物油在纯去离子水中或在已经用HCl或NaOH将其pH调至5-10范围内的去离子水中轻轻或剧烈混合时,得到看起来均匀的混合物。“看起来均匀的”是指通过防止任何明显的“分层”、漂浮或肉眼可见的相分离,使得所述混合物在室温和常压保持相稳定至少1周和优选至少1个月的时段。
在本发明中可用的聚合乳化剂可以具有大于约1000道尔顿(诸如大于约5000道尔顿)的重均分子量。在某些情况下,在本发明中可用的聚合乳化剂是完全交联的,且因此具有无限分子量。
聚合乳化剂包括例如疏水地修饰的、交联的、阴离子的丙烯酸共聚物,包括无规聚合物,但是也可以以其它形式(诸如嵌段聚合物、星形聚合物、接枝聚合物等)存在。
在一个实施例中,所述疏水地修饰的、交联的、阴离子的丙烯酸共聚物可以从至少一种酸性单体和至少一种疏水的烯属不饱和单体合成。合适的酸性单体的例子包括可以被碱中和的那些烯属不饱和酸性单体。合适的疏水的烯属不饱和单体的例子包括含有疏水链的那些,所述疏水链具有至少约3个碳原子的碳链长度。合适的疏水地修饰的丙烯酸聚合物的一个例子是丙烯酸酯/C10-30烷基丙烯酸酯交联聚合物,诸如可从LubrizolCorporation of Ohio得到的PEMULEN TR-1。
根据其它实施例,所述聚合乳化剂是基于丙烯酰氨基烷基磺酸和环状N-乙烯基羧酰胺的水溶性的或水可溶胀的共聚物,诸如商购可得的ClariantCorporation生产的AVC;基于丙烯酰氨基烷基磺酸和疏水地修饰的甲基丙烯酸的水溶性的或水可溶胀的共聚物,诸如商购可得的Clariant Corporation生产的HMB;或丙烯酰氨基烷基磺酸的同聚物,诸如商购可得的Grant Industries,Inc.生产的Granthix APP。根据其它实施例,所述聚合乳化剂是乙基纤维素聚合物。
所述组合物中的聚合乳化剂的量可以在例如按所述组合物重量计约0.1%至约5%的范围内。在某些实施例中,所述聚合乳化剂的量为按所述组合物重量计约0.25%至约3%,诸如约0.5%至约1%。可以使用一种或超过一种聚合乳化剂。
低油
尽管本发明的组合物包含高碳链酯,但是它们是低油组合物。“低油”是指所述组合物中的油的量不过多;具体地,所述组合物中的油的总量(包括所述高碳链酯)小于按所述组合物重量计约5%。
本文中使用的“油”是指疏水化合物,其包括烃油诸如矿物油、矿脂、植物油(例如甘油三酯诸如辛酸/癸酸三酸甘油酯)和其它脂肪酸酯混合物,所述脂肪酸酯包括但不限于甘油酯和高粘度硅油,诸如在序列中具有6个或更多个烷基硅氧基的那些硅油和/或在标准温度和压力具有350厘沲或更高的粘度的那些硅油。烃油具有至少8的碳链长度,且在某些实施例中具有至少11的碳链长度,其中没有碳是羰基碳或具有与其直接键合的亲水部分(上面关于所述高碳链酯所述)。在油的定义中也包括满足上述要求且在室温为固体的化合物(经常被称作“蜡类”)。如本文中所述的“油”不包括这样的化合物:其碳链需要芳基才能实现至少8个碳或至少11个碳的限度。
单体乳化剂
本发明的组合物基本上不含单体乳化剂。单体乳化剂是适合用于乳化连续水相中的不连续油相微滴(或反之亦然)的非聚合化合物。具体地,单体乳化剂能够使得按重量计1%的矿物油在纯去离子水相中的混合物具有稳定性。单体乳化剂可以具有小于5000道尔顿(诸如小于1000道尔顿)的分子量。
常见的单体乳化剂是两亲分子,且可以是阴离子的、非离子的、阳离子的或两性的。阴离子乳化剂包括多种化学类别的特定分子,例如,烷基硫酸盐、烷基醚硫酸盐、烷基单甘油基醚硫酸盐、烷基磺酸盐、烷基芳基磺酸盐、烷基磺基琥珀酸盐、烷基醚磺基琥珀酸盐、烷基磺基琥珀酰胺酸盐、烷基酰氨基磺基琥珀酸盐、烷基羧酸盐、烷基酰氨基醚羧酸盐、烷基琥珀酸盐、脂肪酰基肌氨酸盐、脂肪酰基氨基酸、脂肪酰基牛磺酸盐、脂肪烷基磺基乙酸盐、烷基磷酸盐。
非离子乳化剂可以包括例如酰胺乙氧基化物、甘油单酯乙氧基化物、脱水山梨糖醇酯乙氧基化物、烷基多糖苷、它们的混合物等。某些其它特别的非离子乳化剂包括:多元醇酯的聚氧乙烯衍生物,其中多元醇酯的聚氧乙烯衍生物(1)源自以下(a)和(b),(a)含有约8至约22个、诸如约10至约14个碳原子的脂肪酸,(b)选自以下的多元醇:山梨醇、脱水山梨糖醇、葡萄糖、α-甲基葡萄糖苷、每个分子平均具有约1至约3个葡萄糖残基的聚葡萄糖、甘油、季戊四醇以及它们的混合物,(2)平均含有约10至约120个、诸如约20至约80个环氧乙烷单元;并且(3)每摩尔多元醇酯的聚氧乙烯衍生物平均具有约1至约3个脂肪酸残基;烷基葡萄糖苷或聚葡萄糖苷,它们是以下(a)与(b)的缩合产物:(a)包含约6至约22个、诸如约8至约14个碳原子的长链醇,(b)葡萄糖或含葡萄糖的聚合物;有机硅乳化剂,诸如聚乙二醇、聚丙二醇或聚甘油基酯的交联的或非交联的有机硅共聚物。
两性乳化剂可以包括:1)同时含酸位点和碱位点的分子,例如同时含氨基(碱性)和酸(例如,羧酸,酸性)官能团的氨基酸;或2)在同一分子中同时具有正电荷和负电荷的两性分子。后者的电荷或依赖于组合物的pH或不依赖于组合物的pH。两性材料的例子包括但不限于烷基甜菜碱和酰氨基烷基甜菜碱。本文中公开的两性表面活性剂没有抗衡离子。本领域的技术人员能容易地认识到,在本发明组合物的pH条件下,两性表面活性剂通过具有平衡正电荷和负电荷而呈电中性,或者它们具有抗衡离子如碱金属、碱土金属或铵抗衡离子,两性羧酸盐,诸如烷基两性乙酸盐(单或双);烷基甜菜碱;酰氨基烷基甜菜碱;酰氨基烷基磺基甜菜碱;两性磷酸盐;磷酸化咪唑啉,如磷酸甜菜碱和焦磷酸甜菜碱;羧基烷基烷基多胺;烷基亚氨基-二丙酸盐;烷基两性甘氨酸盐(单或双);烷基两性丙酸盐(单或双);N-烷基β-氨基丙酸;烷基聚氨基羧酸盐。
阳离子乳化剂可以包括烷基季铵盐(单、双或三)、苄基季铵盐、酯季铵盐、乙氧基化的季铵盐、烷基胺等。
本文中使用的“基本上不含单体乳化剂”是指当将任何聚合乳化剂从所述组合物中除去并用水替代时,所述组合物中的单体乳化剂的量不足以使得所述组合物具有相稳定性。在某些其它实施例中,单体乳化剂的量小于按所述组合物重量计约1%。在某些其它实施例中,单体乳化剂的量小于所述组合物中的聚合乳化剂的量。在其它实施例中,所述组合物不含单体乳化剂。
局部用组合物
所述组合物也包含水。在一个实施例中,所述组合物包含按重量计至少约70%的水。
所述组合物局部地施用于人皮肤和/或毛发。所述组合物还可包含按所述组合物重量计约50%至约99.99%(例如,按所述组合物重量计约80%至约99.9%)的其它成分,诸如保湿剂、螯合剂(例如,EDTA)、pH调节剂(例如,柠檬酸、氢氧化钠)、防腐剂(例如,氯苯甘醚)、质感助剂/皮肤调理剂(例如,淀粉聚合物、阳离子化合物等)、低粘度有机硅氧烷、其它皮肤有益试剂等。
合适的保湿剂包括二醇类诸如甘油、丁二醇、丙二醇、聚乙二醇(n=200-600)、聚丙二醇(n=425-2025)、1,2,4-丁三醇、山梨醇酯、1,2,6-己三醇、脲、以及它们的混合物。所述保湿剂可以按所述组合物重量计约1%至约20%(诸如约2%至约12%,诸如约3%至约10%)的量存在。
合适的低粘度有机硅氧烷包括低粘度聚二甲基硅氧烷和在序列中具有约5个或更少的烷基硅氧基的其它有机硅。例子包括:得自Dow Corning的DC200Fluid、50cst和DC2-1184。
在一个实施例中,所述组合物还包含除了4-取代的间苯二酚以外的皮肤有益试剂。本文中使用的“皮肤有益试剂”是对皮肤或毛发具有化妆或治疗效果的化合物(例如,合成的化合物或分离自天然来源或天然提取物的化合物),包括但不限于抗痤疮剂、抗炎剂、外用镇痛药、防晒剂、抗氧化剂、角质层分离剂、维生素(例如,维生素D、维生素B、维生素A)、抗老化活性物(包括皮肤紧致剂、胶原促进剂、弹性蛋白促进剂、皮肤增亮剂等)。所述额外的皮肤有益试剂通常以按所述组合物重量计约0.001%至约20%(例如,按所述组合物重量计约0.005%至约10%诸如约0.01%至约5%)的量存在于所述组合物中。
可使用普通技术人员众所周知的方法制备本发明的组合物。
使用方法
可以将本发明的组合物局部地施用于哺乳动物皮肤。在一个实施例中,所述皮肤需要处理一种或多种如上所述的皮肤老化征象。在一个实施例中,可以将所述组合物施用至需要处理纹线和皱纹和/或弹性缺失的皮肤。根据合适的处理方案,例如,从多至每天2次到少至每3天1次等,可以将所述组合物施用至需要这种处理的皮肤。
在某些实施例中,本发明的组合物还可用于处理与皮肤相关的其它需要状态。例如,本发明的组合物可用于处理炎症后色素沉着过度,用于减小毛孔大小,用于减少皮脂产生,和用于减轻疤痕。
据信,本领域技术人员基于本文中的描述可以在最完全程度上使用本发明。下述的具体实施例应当解释为仅仅是示例性的,无论如何不以任何方式限制本公开内容的其它部分。下述非限制性实例进一步例证了本发明。
实例I:测试组合物的制备
使用下面表1中的4-己基间苯二酚、辛基十二醇新戊酸酯、高碳链酯和其它组分制备了根据本发明的组合物1。
在主容器中,装入水,并开始混合。加入VERSENE NA和氯苯甘醚。缓慢地加入PEMULEN TR-1,并混合至分散。然后将该容器加热至70-75℃,在此时加入OLIVEM1000,并混合至均匀。然后将容器冷却至60-65℃,在此时加入ARISTOFLEX AVC,并混合至完全分散。然后加入EUXYL PE9010,并混合至均匀。然后将容器冷却。在55-60℃,加入DC200Fluid50cst,并混合5分钟。然后加入DC2-1184,并混合至均匀。一旦温度达到40℃以下,使用20%氢氧化钠溶液将pH调至4.9-5.2。然后,加入Advanced Moisture Complex w、NAB Mushroom、亚麻籽油、维生素D、泛醇和香料,并混合至均匀。通过混合至均匀且无块,制备丁二醇和DRY FLO PURE的预混物。将其加入主容器中,并混匀。然后加入4-己基间苯二酚预混物(预先如下制备:在通风柜下,将4-己基间苯二酚加入甘油中,加热至40℃,并混合至完全溶解),并混合至均匀。然后加入ELEFAC,并用Silverson匀浆器在约3000rpm均质化3min。
表1:组合物1
Figure BDA0000386745560000111
PEMULEN TR-1可得自Lubrizol,Wickliffe,Ohio。OLIVEM TR-1可得自B&T Srl,Arcore,意大利。ARISTOFLEX AVC可得自ClariantCorporation Charlotte,North Carolina。EUXYL PE9010可得自Schulke&Mayr GmbH,Norderstedt,德国。DC200Fluid和DC2-1184可得自DowCorning,Midland,Michigan。Advanced Moisture Complex w和Vitamin D3可得自BASF,Ludwigshafen,德国。NAB Mushroom PF可得自ArchLonza,Basel,瑞士。Paraoil Flaxseed Oil可得自Paradigm Science:Benxi,中国。SYNOVEA HR可得自Sytheon,Lincoln Park,NJ。COVSAT可得自Vivimed labs LTD,Bonthapally Village,印度。DRY-FLOPURE可得自AkzoNobel,Chicago,Illinois。VERSENE NA可得自DowChemical,Midland,Michigan。ELEFAC I-205是辛基十二醇新戊酸酯,即可从Alzo International Inc.,Sayerville,New Jersey商购得到的C25酯。
通过改变辛基十二醇新戊酸酯的量和用水调节,或者用不同的酯替换辛基十二醇新戊酸酯来制备其它组合物。所述组合物列在表2中。组合物2-6是根据本发明(组合物3和4都包含3%辛基十二醇新戊酸酯)。比较组合物C1-C4不包含高碳链酯。
表2:
组合物
比较组合物C1(对照)
组合物1 0.1%辛基十二醇新戊酸酯
组合物2 1%辛基十二醇新戊酸酯
组合物3 3%辛基十二醇新戊酸酯
组合物4 3%辛基十二醇新戊酸酯
组合物5 10%辛基十二醇新戊酸酯
组合物6 3%季戊四醇四乙基己酸酯
比较组合物C2 3%新戊二醇二庚酸酯
比较组合物C3 3%C12-C15烷基苯甲酸酯
比较组合物C4 3%异壬酸异壬酯
季戊四醇四乙基己酸酯得自DUB PTO,即可商购得自AlzoInternational Inc.,Sayerville,New Jersey的C37酯。7新戊二醇二庚酸酯得自LEXFEEL,即得自Inolex Chemical Company,Philadelphia,Pennsylvania的C7-C12酯。C12-C15烷基苯甲酸酯得自FINSOLV TN,即得自Innospec Inc.,Newark,Delaware的C19-C22酯。异壬酸异壬酯得自DUB ININ,即可商购得自Stearinerie Dubois Inc.,Ciron,法国的C18酯。
实例II:IL-8测定
如下对实例I的组合物进行IL-8测定,以研究促炎症介质在人上皮细胞中的释放。
从MatTek(Ashland,MA)购买表皮等同物(EPI200HCF),即由正常的人表皮角质形成细胞组成的多层和分化表皮。收到以后,将表皮等同物在不含氢化可的松的维持培养基中在37℃温育24小时。用实例1的制剂局部地处理等同物(2mg/cm2)2小时,然后暴露于100ng/mL肿瘤坏死因子-α(TNFα,可得自Sigma-Aldrich,St Louis,MO)。将等同物与维持培养基一起在37℃温育4小时,然后使用商购可得的试剂盒(UpstateBiotechnology,Charlottesville,VA)分析上清液中的IL-8细胞因子释放。相对于比较组合物C1(没有酯),计算所述组合物的IL-8减少百分比:
减少百分比=[1-(值样品/值基础)]x100
其中值样品是测试的组合物的IL-8水平,并且值基础是比较组合物C1的IL-8值。结果显示在表3中。
表3:
Figure BDA0000386745560000141
尽管已知4-己基间苯二酚会提供抗老化活性,这些结果指示,与仅包含4-己基间苯二酚的组合物相比,包含4-己基间苯二酚、且也包含辛基十二醇新戊酸酯、高碳链酯的组合物表现出增加的IL-8抑制活性。所述抗老化活性通常还随着所述组合物中的辛基十二醇新戊酸酯的量而增加。
实例III:IL-8测定
如在实例II中所述,进行了其它IL-8测定。将包含4-己基间苯二酚和各自以按重量计3%存在的不同酯的组合物(描述于表2中)与根据本发明的包含按重量计3%的季戊四醇四乙基己酸酯的组合物6进行了比较。结果显示在表4中。
表4:
Figure BDA0000386745560000151
从上面的数据可以看出,具有高碳链的酯(分别具有25和37个碳的辛基十二醇新戊酸酯和季戊四醇四乙基己酸酯)会提供与不含这些酯的组合物相比4-己基间苯二酚的活性的大幅增强。即使当以相对较高的浓度使用时,具有更低碳链的酯,即新戊二醇二庚酸酯、C12-C15烷基苯甲酸酯和异壬酸异壬酯(分别具有7-12、19-22和18个碳),仅给4-己基间苯二酚的活性提供不大的增强,或者根本没有增强。
应当理解,尽管已经结合其详细说明描述了本发明,但是前述描述旨在例证而非限制本发明的范围,本发明的范围由所附权利要求书限定。其它方面、优点和修改均在权利要求书内。

Claims (10)

1.一种组合物,包含:
水;
按重量计约0.1%至约0.4%的4-取代的间苯二酚;
具有至少约25个碳原子的酯;和
聚合乳化剂,
其中所述组合物包含按重量计小于约5%的油并且基本上不含单体乳化剂。
2.根据权利要求1所述的组合物,包含按重量计小于约1%的单体乳化剂。
3.根据权利要求1所述的组合物,其中所述酯具有约25至约100个碳原子的碳链长度。
4.根据权利要求1所述的组合物,其中所述酯包含1-4个酯基。
5.根据权利要求1所述的组合物,其中所述酯仅包含氢、碳和氧原子。
6.根据权利要求1所述的组合物,其中所述酯是非离子的并且不含亲水部分。
7.根据权利要求1所述的组合物,包含按重量计约0.1%至约5%的酯。
8.根据权利要求1所述的组合物,包含按重量计至少约70%的水。
9.根据权利要求1所述的组合物,包含约0.2%至约0.4%的4-取代的间苯二酚。
10.根据权利要求1所述的组合物,其中所述4-取代的间苯二酚是4-己基间苯二酚。
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