CN103919767A - 用芳香皮肤活性成份治疗皮肤的方法 - Google Patents
用芳香皮肤活性成份治疗皮肤的方法 Download PDFInfo
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- CN103919767A CN103919767A CN201410115268.XA CN201410115268A CN103919767A CN 103919767 A CN103919767 A CN 103919767A CN 201410115268 A CN201410115268 A CN 201410115268A CN 103919767 A CN103919767 A CN 103919767A
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Abstract
一种用于治疗皮肤、减小对皮肤氧化伤害、降低皮肤细胞中脂氧酶(LO)活性、降低皮肤细胞中环氧化酶(COX)活性、降低皮肤细胞中肿瘤坏死因子-α(TNF-α)活性、或降低皮肤细胞中基质金属蛋白酶(MMP)活性的方法,该方法包括将皮肤或皮肤细胞与芳香皮肤活性成份接触。
Description
本申请是申请日为2008年5月20日,发明名称为“用芳香皮肤活性成份治疗皮肤的方法”的中国专利申请号200810100531.2的分案申请。
技术领域
本发明一般涉及治疗皮肤的方法。特别地,本发明关于局部皮肤护理的组合物,其含有对皮肤产生有益效果的成分。
背景技术
在美容业内,某些成份(包括皮肤活性和非活性成份)具有难闻的味道。这些成份包括含氮化合物、杂环化合物以及含硫化合物。最终的结果就是美容组合物产品具有恶臭味。
气味中和成份常被用来减少或掩盖恶臭味的美容组合物。芳香化合物及这些化合物的混合物的使用在这方面具有一定的成效。可在InternationalCosmetic Ingredient Dictionary and Handbook,10th Edition(2004)中找到这些成份的例子。
因此,使用恶臭性的皮肤活性成份带来的问题之一就是需要加入其它的化学成份来掩盖那些由皮肤活性成份所引起的难闻的气味。
发明内容
发明者们已发现那些以前被认为只可作为气味中和剂的芳香化合物的新用途。在这点上,发明者们已确认出一些不仅在保养皮肤或皮肤细胞或防止皮肤或皮肤细胞损害上具有药妆品效果,同时还能够减少、掩盖或防止美容组合物(如芳香皮肤活性成份或化合物)的恶臭味强度的芳香化合物。因此,在使用本发明芳香皮肤活性成份的情况下,本发明的组合物可免去气味中和剂的使用或减少其使用量。然而,发明者们考虑到气味中和剂在组合物中的使用,该组合物也含有本说明书中所有公开的芳香皮肤活性成份。
在一个非限制性方面,这里公开了一种治疗或预防皮肤病症的方法,该方法包括在皮肤上局部涂敷含芳香皮肤活性成份组合物,其中该组合物的局部涂敷可治疗或预防皮肤病症。在某些实施方式中,在皮肤上涂敷含药妆有效量的芳香皮肤活性成份。药妆有效量的非限制性例子包括占组合物重量的0.005%~2.0%(注意其他范围也涵括在内,并在本说明书中公开)。在某些非限制性方面,芳香皮肤活性成份可从下述表1中确认的基团中选择(如1,4-二氧杂环十七烷-5,17-二酮;(3E)-4-(2,6,6-三甲基-1-环已烯-1-基)-3-丁烯-2-酮;1-(1,2,3,4,5,6,7,8-八氢-2,3,8,8-四甲基-2-萘基)乙-1-酮;1-(2,3,8,8-四甲基-1,2,3,5,6,7,8,8a-八氢萘-2-基)乙酮;1-(2,3,8,8-四甲基-1,2,3,4,6,7,8,8a-八氢萘-2-基)乙酮;4-甲基-3-癸烯-5-醇;2,6-二甲基-5-庚烯醛;3,3-二甲基-5(2,2,3-三甲基-3-环戊烯-1-基)-4-戊烯-2-醇;3-己烯-1-醇(E)以及(Z);甲基3-氧代-2-戊基环戊烷羧酸酯;4-乙基-3,7-二甲基辛-1,6-二烯-3-醇;2-异丁基-4-甲基四氢-2H-吡喃-4-醇;α-甲基-1,3-苯并二噁茂-5-丙醛;5-庚基二氢呋喃-2(3H)-酮;3-(4-异丙基苯基)-2-甲基丙醛;2-甲基癸醛;2,4-壬二烯-1-醛;2-十二烯醛(E);2,6-壬二烯-1-醛(反式,反式;反式,顺式);1-十二醛;4-叔-丁基环己基乙酸酯;2-壬烯酸甲酯;1-甲基-3-(4-甲基戊-3-烯基)环己-3-烯甲醛;3a,4,5,6,7,7a-六氢-4,7-亚甲基-1h-茚-5(或6)-基醋酸酯;3-(4-乙苯基)-2,2-二甲基丙醛;3-(2-乙苯基)-2,2-二甲基丙醛;(Z)-4-甲基-3H-苯并[c][1,2]二氧杂环庚-3-酮;醋酸顺-2-己烯酯;(Z)-2-(丁-2-烯基)-3-甲基环戊-2-烯酮;甲基2,2-二甲基-6-亚甲基环己烷羧酸酯;(Z)-5-(羟基亚氨基)辛-3-酮;(2,4,6-)三甲基-3-环己烯-1-甲醛;(3,5,6-)三甲基-3-环己烯-1-甲醛;5-戊基二氢呋喃-2(3H)-酮;顺-6-壬烯醛;乙基3-异丙基二环[2.2.1]庚-5-烯-2-羧酸酯;以及3,7-二甲基-6-辛-1-基醋酸酯)。该组合物可含有单一的芳香皮肤活性成份或芳香皮肤活性成份的任何组合。例如,该组合物可含有至少1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29或30种芳香皮肤活性成份,包括这些成份的任何组合。皮肤病症的非限制性例子包括搔痒症、微血管扩张、雀斑、老年斑、老年性紫癜、角质疣、黑细胞、小脓疱、小皱纹或皱纹、瘤、太阳晒伤的皮肤、皮炎(包括但不限于脂溢性皮炎、钱币状皮炎、接触性皮炎、异位性皮炎、剥脱性皮炎、口周皮炎以及淤滞性皮炎)、牛皮癣、毛囊炎、红斑痤疮、痤疮、脓疱病、丹毒、红癣、湿疹以及其它的炎性皮肤病症。在某些非限制性方面,皮肤病症可能是由于暴露于紫外光、老化、辐射、长时间太阳光照射、环境污染、空气污染、风吹、冷、热、化学品、疾病治疗、吸烟或缺少营养而引起。皮肤可为面部皮肤或非面部皮肤(如胳膊、腿、手、胸部、背部、足部等)。该方法可进一步包括对一个人是否需要进行皮肤治疗进行鉴别。此人可为男性或女性。此人的年龄至少为1,2,3,4,5,6,7,8,9,10,15,20,25,30,35,40,45,50,55,60,65,70,75,80,85,90,95或更大或这些数字范围内的任何年龄。另一方面,该方法还包括在局部涂敷有效量的药物来:提高皮肤角质层的代谢率;提高纤维原细胞的胶原蛋白合成;提高细胞的抗氧化能力(如外加的抗氧化能够帮助、补充或防止细胞抗氧化剂的缺失,如皮肤细胞(如角化细胞、黑素细胞、朗格汉斯细胞等)中的抗氧化剂如氢酶和谷胱甘肽);抑制黑素细胞中的黑色素形成;减少或防止氧化对皮肤造成的损害(包括减少皮肤中脂类过氧化物的量和/或蛋白质氧化的量)。
另一方面,本发明公开了一种用于降低或消除细胞中脂氧酶、环氧化酶(COX)、肿瘤坏死因子-α(TNF-α),或基质金属蛋白酶(MMP)的活性的方法,该方法包括将细胞与芳香皮肤活性成份接触,其中将细胞与芳香皮肤活性成份接触以降低或消除细胞中脂氧酶、环氧化酶(COX)、肿瘤坏死因子-α(TNF-α)或基质金属蛋白酶(MMP)的酶活性。本发明还公开了一种用于减少或防止细胞中氧化伤害的方法,该方法包括将细胞与芳香皮肤活性成份接触,其中将细胞与芳香成份接触以降低细胞中的氧化伤害。该细胞可为皮肤细胞。皮肤细胞的非限制性例子包括人的表皮角化细胞、人的真皮纤维原细胞,或人的黑素细胞。环氧化酶的非限制性例子包括环氧化酶-1或环氧化酶-2。基质金属蛋白酶的非限制性例子包括MMP3或MMP9。芳香皮肤活性成份可选自于下面表I中所确认的物质所组成的组。芳香皮肤活性成份被包含在一种组合物中。细胞可与单一的芳香皮肤活性成份或芳香皮肤活性成份的任何组合物接触。例如,细胞可接触至少1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29或30种芳香皮肤活性成份,包括这些成份的任何组合。
在某些实施方式中,本发明的组合物可降低皮肤中内部氧化和/或外部氧化的伤害。在其它方面,该组合物可增加细胞中胶原蛋白的合成。该组合物还可降低皮肤炎症,如通过降低细胞中炎性细胞因子的形成来达到。这些细胞的非限制性例子包括人的表皮角化细胞、人的纤维原真皮细胞、人的黑素细胞,人细胞衍生的三维活体外组织等同物包含人的表皮角化细胞、人的纤维原细胞,或人的黑素细胞,或这些细胞的任何组合(如人的表皮角化细胞和人的纤维原细胞的组合或人的表皮角化细胞和人的黑素细胞的组合)。
还公开了一种亮白皮肤或均匀肤色的方法,该方法包括本发明的组合物涂敷于皮肤。该方法还进一步包括鉴别一个人是否需要亮白皮肤或均匀肤色。这些方法还进一步包括抑制皮肤细胞中的黑素生成、抑制皮肤细胞中的酪氨酸酶或酪氨酸酶的合成,或抑制黑色素转移到皮肤的角化细胞中。组合物可作为α黑色素刺激荷尔蒙的拮抗剂。该组合物甚至可去除皮肤上的色素沉着。在非限制性方面,亮白皮肤可包括减少老年斑、皮肤变色或雀斑的出现。
还公开了一种治疗色素沉着过度的方法,该方法包括在皮肤上涂敷本发明的组合物。该方法还包括对一个人是否需要治疗色素沉着过度进行鉴别。发明者们还考虑到的其它方法包括减少老年斑、皮肤变色或雀斑出现,减少或防止皮肤上细纹或皱纹的出现,或增加皮肤的弹性的方法。
本发明的另一方面包括一种组合物,其含有有效量的芳香皮肤活性成份或这些成份的组合。该组合物可为局部皮肤护理组合物。芳香皮肤活性成份可从含有下述表1中确认的物质组成的组中选择。该组合物可不含香味。在某些方面,该组合物不包含另一种芳香化合物。该组合物在某些实施方法中不包括另一种皮肤活性成份和/或不包括另一种芳香化合物。该组合物可含有单一的芳香皮肤活性成份或芳香皮肤活性成份的任何组合。例如,该组合物可含有至少1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29或30种芳香皮肤活性成份,包括这些成份的任何组合。芳香皮肤活性成份的组合可协同发挥或以互补的方式产生效果,这种效果超过任一种组份单独使用时所期望产生的效果。非限制性协同效果的例子包括减少内部或外部的氧化损害,增加胶原蛋白的生成,减低炎性反应以及抑制黑素生成或降低或消除皮肤中脂氧酶、环氧化酶(COX)、肿瘤坏死因子-α(TNF-α)或基质金属蛋白酶(MMP)的活性。在某些实施方式中,组合物配制成局部皮肤护理组合物。这些组合物可为化妆组合物。在其它方面,组合物可配制成乳液(如水包油以及油包水乳液)、面霜、洗液、溶液(如水性或水醇溶液)、无水基质(如唇膏或粉末)、凝胶,以及油膏。在其它的非限制性实施方式中,本发明的组合物可含于抗衰老、清洁或保湿产品中。该组合物还可配制成局部皮肤涂敷使用,其在一天中可使用至少1,2,3,4,5,6,7或更多次。在本发明的其它方面,组合物可为储存稳定的或颜色稳定的,或兼而有之。还考虑到可通过对组合物的粘度进行选择获得到期望的效果(如取决于期望的组合物类型、这种组合物的粘度可从约1cps到超过1百万cps或其中的任何范围和整数(如2cps,3,4,5,6,7,8,9,10,20,30,40,50,60,70,80,90,100,200,300,400,500,600,700,800,900,1000,2000,3000,4000,5000,6000,7000,8000,9000,10000,20000,30000,40000,50000,60000,70000,80000,90000,100000,200000,300000,400000,500000,600000,700000,800000,900000,1000000cps等,上述值是在Brookfield粘度计上使用TC轴在25℃以2.5rpm下测得))。本发明的组合物也可经改性从而具有期望的氧自由基吸收能力(ORAC)值。在某些非限制性方面,本发明的组合物可经改性从而具有一定的ORAC值,对每mg组合物而言,ORAC值至少约1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,35,40,45,50,55,60,70,80,90,95,100,200,300,400,500,600,700,800,900,1000,2000,3000,4000,5000,6000,7000,8000,9000,10000,15000,20000,30000,50000,100000或更多,或位于其中的任何范围内。在非限制性方面,组合物具有约6~约9的pH值。在其它的方面,pH值可为1,2,3,4,5,6,7,8,9,10,11,12,13或14。在其它的方面,组合物可作为遮光剂,其具有的防晒因子(SPF)为1,5,10,15,20,25,30,35,40,45,50,55或更高。在某些方面,组合物除了包括本说明书中揭露的芳香皮肤活性成份,还包括气味中和剂。
另外还涵盖了包括本发明组合物的试剂盒。在某些实施方式中,组合物放置于一容器中。该容器可为一瓶子、分配器或包装盒。该容器可分布预定量的组合物。在某些方面,组合物以喷雾、团状物或液体的形式分送。容器可在其表面上具有标记。该标记可为文字、缩写、图片或符号。
另外还涵盖了包括本发明组合物的产品。在非限制性方面,该产品可为化妆品。化妆品可以是本说明书的其它部分所描述的化妆品或本领域人员熟知的化妆品。产品的非限制性例子包括保湿液、面霜、洗液、皮肤柔润剂、粉底霜、晚霜、唇膏、清洁剂、收敛剂、防晒剂、面膜或抗老化产品。
可假定本说明书中讨论的任一实施方式均可通过本发明中的任何方法或组合物来实施,反之亦然。此外,本发明中的组合物也可用于得到本发明中的方法。
本领域技术人员可以理解,术语“大约”或“近似”被定义为接近,并且在非限制性的实施方式中,这些术语被定义为在10%以内,优选为在5%以内,更优选为在1%以内,最优选为在0.5%以内。
当术语“抑制”或“降低”或任何这些术语的任何变形被用在权利要求和/或说明书中时,均包括为了达到预期的结果所采用的任何可测的降低或完全的抑制。
当术语“有效的”被用在说明书和/或权利要求中时,表示足以取得预期的、期望的或希望的结果。例如,“有效量”或“药妆有效量”或“治疗有效量”表示为达到预期的、期望的或希望的结果所需要的足够量。本方法中芳香皮肤活性成份和本发明中的组合物的使用可包括“有效量”或“药妆有效量”或“治疗有效量”。这种数量上的改变根据芳香皮肤活性成份、治疗或防止的条件以及其程度、使用的方式和被治疗人的年龄而变化,但是本领域技术人员可根据自身的经验以及本公开对该数量进行常规确定。
在权利要求和/或说明书中将不定冠词与术语“包含”一起使用时表示“一个”,但也可表示“一个或多个”、“至少一个”和“一个或多于一个”的意思。
除非明确说明二者只能选其一,否则权利要求中使用的术语“或”即表示“和/或”,尽管在公开中支持的定义仅指二者取其一以及“和/或”。
本说明书和权利要求中使用的术语“包含”(以及其不同时态形式)、“具有”(以及其不同时态形式)、“包括”(以及其不同时态形式)或“含有”(以及其不同时态形式)均表示包括的或开放式的意思,且不排除其它的、未例举的元素或方法步骤。
从下面详细的描述中可以看出本发明的其它目的、特性以及优点。然而应当理解的是,本发明的详细描述和实施例当表示具体的实施方式时,其仅以说明的方式给出。此外,从这些详细的描述中,本领域技术人员将显而能在本发明的精神和范围内作出各种变化和改性。
具体实施方式
在今天注重形象的社会,人们总在不停地寻找能够改善他们皮肤视觉外观的产品。许多时候,不美观的皮肤与皮肤老化、肤色不均匀或皮肤受到环境因素的伤害,如紫外光、长时间太阳光照射、环境污染、化学品、疾病病状或吸烟有关。以前对改善皮肤视觉外观的尝试常常用到发出难闻或有臭味的皮肤活性成份。
发明者们已发现了以前被认为只可作为气味中和剂的芳香化合物的新用途。如在下述部分的非限制方面中解释的,由发明者们发现的芳香皮肤活性成份在治疗很广范围内的皮肤疾病以及防止皮肤损害方面有效。这些化合物可以添加到所有类型的美容组合物中。在下述进一步的非限制性细节中将对本发明的这些方面以及其它方面进行描述。
A.芳香皮肤活性成份
发明者们已发现表1中列出的化合物具有令人吃惊的以及意想不到的对人的皮肤有益的性质。在下面的实施例部分中将该处支持这些性质的数据(包括如何获得这些数据),这些实施例在此引用并被并入参考本部分。这些化合物的有益的性质包括降低或防止皮肤或皮肤细胞受到的氧化伤害、降低或防止皮肤或皮肤细胞中脂氧酶的活性、降低或抑制皮肤或皮肤细胞中环氧化酶(COX)的活性、降低或抑制皮肤或皮肤细胞中的肿瘤坏死因子-α(TNF-α),以及降低或抑制皮肤或皮肤细胞中的基质金属蛋白酶(MMP)的活性。
表1
(芳香皮肤活性成份)
芳香皮肤活性化合物及其衍生物和改性可使用常规化学合成技术来制备(例如可参考Organic Chemistry,5th Ed,其以引用的方式而并入)。
1.皮肤细胞中的氧化损伤
自由基是化学活性分子片段,其由于具有多余电子或缺少电子而带有电荷。活性氧类(ROS)为含氧的自由基,其通过内源性(细胞的)和外源性(环境的)机理对人体皮肤细胞造成氧化损伤。在老化的皮肤中,累积的氧化损伤导致皮肤失去弹性并且增加细纹和皱纹。抗氧化剂通过中和或降低自由基的能量来阻止氧化过程,从而保护细胞功能并防止对细胞蛋白的损害。因此,减少皮肤中氧化损伤可减少过早的衰老的迹象。
2.脂氧酶
脂氧酶催化花生四烯酸氧化转变成羟化二十烷四烯酸(HETE),其随后转变成类脂化合物。花生四烯酸浓度的增加与人皮肤中持续的炎症密切相关。因此,能够降低脂氧酶活性的化合物可用作皮肤炎症的有效介质。
3.环氧化酶(COX)
COX是双功能酶,其展示出环氧化酶和过氧化酶的功能。环氧化酶可将花生四烯酸转变为氢过氧基环内过氧化物(前列腺素G2;PGG2)并且过氧化酶将环内过氧化物(前列腺素H2;PGH2)还原为前列腺素、血栓素、以及前列环素的前体,这些均是皮肤炎症的关键性介体。因此,能够降低COX酶活性的化合物也可用来调节皮肤的炎症反应。
4.肿瘤坏死因子-α(TNF-α)
TNF-α为多效性细胞因子,其在皮肤炎症中扮演中心角色。该因子表达的增强与炎症前期的活性的向上调节有关。因此,能够降低人体表皮角化细胞分泌TN?F-α蛋白的化合物可减少炎症反应,从而减少皮肤红肿以及刺激。
5.基质金属蛋白酶(MMP)
MMP是细胞外蛋白酶,其基质包括含有皮肤真皮间隔膜的细胞外基质蛋白。MMP3基质包括胶原蛋白、纤维连接蛋白,以及层粘连蛋白,而MMP9基质包括胶原蛋白VII、纤维连接蛋白,以及层粘连蛋白。在老化皮肤中,这些酶会破坏那些提供皮肤支持的蛋白质。因此,降低这些酶的活性可抑制对这些蛋白质的损害。因此,能够抑制MMP活性的化合物会增加胶原蛋白以及其它真皮基质蛋白的含量。
B.芳香皮肤活性成份的衍生物和改性
本发明芳香皮肤活性成份的衍生物和改性也涵盖在本发明的范围内。对这些成份进行的改性的非限制性例子包括:添加或去除低级烷基如甲基、乙基、丙基或取代的低级烷基如羟甲基或氨甲基;羧基和羰基;羟基;硝基、氨基、酰胺以及偶氮基;硫酸盐、磺酸盐、烷氧磺基、巯基、磺酰基、亚砜、磷酸盐、膦磺酸基、磷酰基,以及卤素取代基。其他的改性还包括在原子结构中添加或从中删除一个或多个原子,例如,用丙基取代乙基;用更大或更小的芳香基团取代苯基。此外,在单环或双环结构中,可用杂原子如N,S或O来取代碳原子。
C.本发明的组合物
1.成份的结合及用量
本发明的组合物可涵盖的范围包括本说明书内公开的芳香皮肤活性成份的任何组合。此外,该组合物可包括本说明书内所描述的任何数目的添加成份的组合。该芳香皮肤活性成份的浓度和添加成份的浓度可以改变。例如,在非限制性实施方式中,组合物在其最终的形式中可含有芳香皮肤活性成份和添加成份中的至少一种,其比例至少约0.0001%,0.0002%,0.0003%,0.0004%,0.0005%,0.0006%,0.0007%,0.0008%,0.0009%,0.0010%,0.0011%,0.0012%,0.0013%,0.0014%,0.0015%,0.0016%,0.0017%,0.0018%,0.0019%,0.0020%,0.0021%,0.0022%,0.0023%,0.0024%,0.0025%,0.0026%,0.0027%,0.0028%,0.0029%,0.0030%,0.0031%,0.0032%,0.0033%,0.0034%,0.0035%,0.0036%,0.0037%,0.0038%,0.0039%,0.0040%,0.0041%,0.0042%,0.0043%,0.0044%,0.0045%,0.0046%,0.0047%,0.0048%,0.0049%,0.0050%,0.0051%,0.0052%,0.0053%,0.0054%,0.0055%,0.0056%,0.0057%,0.0058%,0.0059%,0.0060%,0.0061%,0.0062%,0.0063%,0.0064%,0.0065%,0.0066%,0.0067%,0.0068%,0.0069%,0.0070%,0.0071%,0.0072%,0.0073%,0.0074%,0.0075%,0.0076%,0.0077%,0.0078%,0.0079%,0.0080%,0.0081%,0.0082%,0.0083%,0.0084%,0.0085%,0.0086%,0.0087%,0.0088%,0.0089%,0.0090%,0.0091%,0.0092%,0.0093%,0.0094%,0.0095%,0.0096%,0.0097%,0.0098%,0.0099%,0.0100%,0.0200%,0.0250%,0.0275%,0.0300%,0.0325%,0.0350%,0.0375%,0.0400%,0.0425%,0.0450%,0.0475%,0.0500%,0.0525%,0.0550%,0.0575%,0.0600%,0.0625%,0.0650%,0.0675%,0.0700%,0.0725%,0.0750%,0.0775%,0.0800%,0.0825%,0.0850%,0.0875%,0.0900%,0.0925%,0.0950%,0.0975%,0.1000%,0.1250%,0.1500%,0.1750%,0.2000%,0.2250%,0.2500%,0.2750%,0.3000%,0.3250%,0.3500%,0.3750%,0.4000%,0.4250%,0.4500%,0.4750%,0.5000%,0.5250%,.550%,0.5750%,0.6000%,0.6250%,0.6500%,0.6750%,0.7000%,0.7250%,0.7500%,0.7750%,0.8000%,0.8250%,0.8500%,0.8750%,0.9000%,0.9250%,0.9500%,0.9750%,1.0%,1.1%,1.2%,1.3%,1.4%,1.5%,1.6%,1.7%,1.8%,1.9%,2.0%,2.1%,2.2%,2.3%,2.4%,2.5%,2.6%,2.7%,2.8%,2.9%,3.0%,3.1%,3.2%,3.3%,3.4%,3.5%,3.6%,3.7%,3.8%,3.9%,4.0%,4.1%,4.2%,4.3%,4.4%,4.5%,4.6%,4.7%,4.8%,4.9%,5.0%,5.1%,5.2%,5.3%,5.4%,5.5%,5.6%,5.7%,5.8%,5.9%,6.0%,6.1%,6.2%,6.3%,6.4%,6.5%,6.6%,6.7%,6.8%,6.9%,7.0%,7.1%,7.2%,7.3%,7.4%,7.5%,7.6%,7.7%,7.8%,7.9%,8.0%,8.1%,8.2%,8.3%,8.4%,8.5%,8.6%,8.7%,8.8%,8.9%,9.0%,9.1%,9.2%,9.3%,9.4%,9.5%,9.6%,9.7%,9.8%,9.9%,10%,11%,12%,13%,14%,15%,16%,17%,18%,19%,20%,21%,22%,23%,24%,25%,26%,27%,28%,29%,30%,35%,40%,45%,50%,60%,65%,70%,75%,80%,85%,90%,95%,或99%或其中的任何衍生的范围或整数。在非限制性方面,这些成份的百分比可通过整个组合物的总重量的重量或体积来计算得到。浓度的变化取决于组合物或加入了该组合物的产品中期望的效果。
2.组合物赋形剂
本发明的组合物可配制到所有类型的赋形剂中。合适的赋形剂的非限制性实施例包括乳液(如油包水、水包油包水、水包油、油包水包油、有机硅包水包油)、乳脂、洗液、溶液(水性和水-醇性)、无水基质(如唇膏和粉末)、凝胶以及油膏或本领域技术人员所知的其它方式或前述各种形式的组合(Remington's,1990)。本领域技术人员将容易认识到上述赋形剂的变化和其他适合的赋形剂并将它们恰当地用于本发明。在某些方面,成份的浓度以及组合可按下面的方式选择,即组合要化学相容并且在最终的产品中不会形成会发生沉淀的复合物。
本发明还涵盖了可将本说明书中确认的芳香皮肤活性成份和添加成份进行包裹,以能够输送到目标区域,如皮肤。封装技术的非限制性例子包括使用脂质体、疱囊,和/或纳米粒子(如可生物降解和非生物降解的胶状粒子,其含有的聚合物材料可将成份封阻、包裹、和/或吸附于其中—例子包括纳米球和纳米胶囊),它们可用作输送式赋形剂而将这些成份输送至皮肤(例如参见美国专利6,387,398;美国专利6,203,802;美国专利5,411,744;Kreuter1998)。
本发明还涵盖制药学上可接受的或药理学可接受的组合物。短语“药学上可接受的”或“药理学上可接受的”包括用于人体时不会产生过敏或类似的不利反应的组合物。通常,这些组合物可制备成局部组合物、液体溶液或悬浮液,也可制备成在使用前适合溶解于或悬浮于液体中的固体形式。施用途径可根据治疗部位和待治疗的疾病的性质而变化,并包括如局部、吸入、皮内、经皮肤、非肠道、静脉内、肌肉、鼻内、皮下、经皮、气管内、腹腔内、瘤内、灌注、灌洗、直接注射以及口服和配方。
3.产品
本发明的组合物可用于产品中。产品的非限制性例子包括化妆品、食品、药品等。仅举例来讲,非限制性的化妆品包括防晒剂产品、无日晒皮肤美黑产品、头发用产品、指甲产品、保湿霜、护肤霜以及洗液、软化剂、日用洗液、凝胶、油膏、妆底、晚霜、唇膏、睫毛膏、眼影、眼线、腮红、清洁剂、调色剂、面膜或其它已知的美容产品及应用。此外,美容产品还可配制成可保留或可冲洗的产品。
4.其它成份
本发明的组合物还包括其它成份。其它成份的非限制性例子包括美容成份(活性和非活性的)以及药用成份(活性和非活性的)。
a.美容成份
CTFA International Cosmetic Ingredient Dictionary and Handbook(2004)中描述了大量可用于本发明的非限制性的美容成份。这些成份类型的例子包括:芳香剂(人造的和天然的)、染料以及色素成份(例如蓝1,蓝1色淀,红40,二氧化钛,D&C蓝4号,D&C绿5号,D&C橙4号,D&C红17号,D&C红33号,D&C紫2号,D&C黄10号,以及D&C黄11号)、吸附剂、乳化剂、稳定剂、润滑剂、溶剂、保湿剂(例如包括润肤剂、湿润剂、成膜剂、封闭剂以及能够影响皮肤自身湿度的试剂)、憎水剂、紫外光吸收剂(物理和化学吸收剂如对胺基安息香酸(“PABA”)以及相应的PABA衍生物、二氧化钛、二氧化锌等)、香精油、维他命(如A,B,C,D,E和K)、痕量金属(如锌、钙和硒)、抗刺激剂(如固醇和非固醇类的抗炎症试剂)、植物提取物(例如真芦荟、甘菊、黄瓜提取液、银杏、人参以及迷迭香)、抗菌试剂、抗氧化剂(例如BHT和生育酚)、螯合剂(例如二钠EDTA以及四钠EDTA)、防腐剂(例如尼泊金甲酯以及尼泊金丙酯)、pH调节剂(例如氢氧化钠和柠檬酸)、吸收剂(例如淀粉辛烯基琥珀酯铝盐、高岭土、玉米淀粉、燕麦淀粉、环式糊精、云母以及沸石)、皮肤漂白和亮白剂(如对苯二酚和烟酰胺乳酸盐)、保湿剂(例如丙三醇、丙二醇、丁二醇、戊二醇、山梨(糖)醇、尿素以及甘露醇)、剥离剂(例如α-羧酸以及β-羧酸如乳酸、乙醇酸以及水杨酸及这些酸的盐)、防水试剂(例如镁/铝氢氧化硬脂酸盐)、润肤剂(例如芦荟提取物、尿囊素、没药醇、神经酰胺、二甲硅油、透明质酸以及甘草酸二钾)、增稠剂(例如可增加组合物粘度的物质如羧酸聚合物、交联聚丙烯酸聚合物、聚丙烯酰胺聚合物、多醣以及树胶)以及含有有机硅的化合物(例如硅油以及聚有机硅氧烷)。
b.药用成份
本发明也涵盖了可与本发明的乳液组合物一起使用的药用成分。药用成份的非限制性例子包括防痤疮试剂、治疗红斑痤疮的试剂、镇痛剂、麻醉剂、直肠用试剂、抗组胺剂、抗发炎试剂包括非固醇类抗炎症药物、抗生素、抗真菌剂、抗病毒剂、抗微生物剂、抗癌活性物质、灭疥癣药、杀虱剂、抗肿瘤药、止汗药、止痒剂、抗牛皮癣药、抗皮脂溢药、生物活性蛋白质以及肽、烧伤治疗试剂、烧灼试剂、褪色剂、脱毛剂、尿疹治疗试剂、酶、生发剂、去发剂包括DFMO及其盐和类似物、止血剂、角质剥脱剂、口腔溃疡治疗试剂、唇疱疹治疗试剂、牙齿和牙周治疗试剂、光敏活性剂、皮肤保护剂/屏障剂、类固醇包括荷尔蒙以及肾上腺酮、晒伤治疗剂、防晒剂、经皮的活性剂、鼻用的活性剂、阴道活性剂、疣治疗剂、伤口处理剂、伤口愈合剂等等。
D.试剂盒
在本发明的某些方面涵盖试剂盒的使用。例如,本发明的组合物可放置于试剂盒内。该试剂盒可包含一个容器。该容器可以包括瓶子、金属管、层压管、塑料管、分布器、加压容器、隔离容器、包装、隔间、唇膏容器、紧凑容器、能够容纳化妆组合物的化妆盘、或其它类型的容器如注射或吹塑的塑料容器,在该塑料容器中容纳有分散液或组合物或期望的瓶子、分布器或包装。试剂盒和/或容器可在其表面含有标记。例如,该标记可为一文字、一短语、一缩写、一图片或一符号。
容器可分配预定量的组合物。在其它的实施方式中,该容器可被挤压(如金属、薄片或塑料管)从而可分配给出期望量的组合物。该组合物可以喷雾、气溶胶、液体、流体或半固体的形式进行分布。容器可装有喷洒、抽吸或挤压机理。试剂盒还可包括使用该试剂盒和/或组合物的说明书。说明书可包括介绍如何涂敷、使用和保存组合物。
实施例
下面的实施例用于对本发明的非限制性方面进行阐述。本领域的技术人员应当认识到,按照发明者发现的代表的技术的实施例中所公开的技术是在本发明的实施中较佳的。然而,本领域的技术人员在阅读了本公开后应当认识到可对具体的实施方式作出许多改变,并在不脱离本发明精神和范围之下仍获得相同的或类似的结果。
实施例1
芳香皮肤活性成份的效验数据
下表2-4提供的数据肯定了上述表1中列出的芳香皮肤活性成份的效力。
表2
表3
表4
实施例2:
效力评估测定
下面的测定用于得到表2~4中所示的结果。
抗氧化剂(AO)测定:一种活体外的生物测定,测量化合物的总的抗氧化能力。该测定依赖于样品中抗氧化剂以抑制(2,2'-连氮基-双-[3-乙基苯并噻吡咯啉磺酸])被正铁肌红蛋白氧化为·+的抗氧化能力。活性有机体的抗氧化系统含有酶例如超氧物歧化酶、过氧化氢酶、以及谷胱甘肽过氧化酶;大分子例如清蛋白、血浆铜蓝蛋白、以及铁蛋白;以及一系列小分子,包括抗坏血酸、α-生育酚、β-胡萝卜素、还原型谷胱甘肽、尿酸以及胆红素。内源性和来自食物的抗氧化剂的总和代表了细胞外液体的总抗氧化能力。在防止受到活性氧或氮自由基的攻击中,所有不同类型的抗氧化剂协同作用可比单独的一种化合物提供了更好的保护。因此,总的抗氧化能力比单组份的测量结果提供了更为相关的生物学信息,这是由于它考虑到了存在于血浆和体液中所有抗氧化剂的累积效果。该测定依赖于样品中抗氧化剂以抑制(2,2'-连氮基-双-[3-乙基苯并噻吡咯啉磺酸])被正铁肌红蛋白氧化为·+的抗氧化能力。将样品中抗氧化剂以防止ABTS氧化的能力与Trolox的抗氧化能力相比,并且用Trolox摩尔当量进行定量,其中Trolox是水溶性的生育酚类似物。
使用抗氧化测定试剂盒(#709001;Cayman Chemicals),对化合物的活体外抑制基质氧化的能力进行测试。正值反映出化合物抑制氧化的能力并且展示出抗氧化剂的能力。
脂氧化酶(LO)测定:活体外脂氧化酶(LO)抑制测定。LO是非血红素含铁的加双氧酶,其能够催化分子氧添加到脂肪酸。亚油酸酯和花生四烯酸酯是LO在动物和植物中的主要基质。花生四烯酸然后可被转变成二十烷四烯酸(HETE)的衍生物,其随后被转变成白三烯这一有效的炎性介体。该测定提供了一种准确便利的筛选脂氧化酶抑制剂的方法,其通过测量脂氧化酶(5-,12-,或15-LO)与花生四烯酸所产生的氢过氧化物来确定。
遵循比色LO抑制剂筛选试剂盒(#760700,Cayman Chemical)的生产厂家说明,将纯化的15-脂氧化酶和测试化合物混合到测定缓冲器中并在室温下摇晃10分钟进行培养。在培养后,加入花生四烯酸以引发反应,并在室温下再对混合物培养10分钟。加入比色基质以终止催化,并且通过荧光板在490nm的读数评定色阶。计算脂氧化酶活性的抑制百分比,并与未经处理的对照相比较从而确定测试化合物抑制纯化酶活性的能力。
环氧化酶(COX)测定:活体外环氧化酶(COX)-1和-2(COX-1,-2)的抑制测定。COX是一种双功能酶,其具有环氧化酶和过氧化酶的活性。环氧化酶活性可将花生四烯酸转变为氢过氧基环内过氧化物(前列腺素G2;PGG2)并且过氧化酶还原内过氧化物(前列腺素H2;PGH2)为相应的醇,即前列腺素、血栓素以及前列环素的前体。这种COX抑制剂筛选测定对环氧化酶中的过氧化酶组份进行测量。通过监控氧化N,N,N',N'-四甲基-对苯二胺(TMPC)的外观来对过氧化酶的活性进行比色测定。为了筛选同工酶特异性抑制剂,该抑制剂筛选测定中包括COX-1和COX-2两种酶。
遵循比色COX(绵羊)抑制剂筛选测定(#760111,Cayman Chemical)的生产厂家说明,将纯化的环氧化酶(COX-1或COX-2),亚铁血红素和测试化合物混合到测定缓冲器中,并在室温下摇晃15分钟进行培养。在培养后,加入花生四烯酸以及比色基质以引发反应,并在室温下再对混合物摇动培养15分钟。通过荧光板在590nm的读数评定色阶。计算COX-1或COX-2活性的抑制百分比,并与未经处理的对照进行对比,从而确定测试化合物抑制纯化酶活性的能力。
肿瘤坏死因子-α(TNF-α)测定:TNF总科的原型配位体TNF-α是一种多效性细胞因子,其在皮肤炎症中扮演着中心角色。该因子的表达的增强与炎症前期活性的向上调节有关。这种生物测定通过人表皮角化细胞分析化合物对生成TNF-α的影响。该测定终点的分光光度测量反映出TNF-α的存在以及细胞存活力。该测定使用了定量夹心酶免疫测定技术,先在微量盘上预涂布对TNF-α特异的单克隆抗体。用吸液管将标准和样品移到孔中,并通过固定的抗体结合任何出现的TNF-α。在洗去任何未结合的物质后,向孔中加入对TNF-α特异的酶连接的多克隆抗体。在洗涤去除任何未结合的抗体酶反应试剂后,向孔中加入底物溶液,在450nm下使用微量盘作检测,显示出的颜色与在起始步骤中结合的TNF-α的量成正比例。当颜色不再变深时测定颜色的强度。
在37℃、5%CO2中,用PMA(10ng/ml,Sigma Chemical,#P1585-1MG)和测试化合物处理在EpiLife标准生长培养基中培养的生长中的正常成人角化细胞(Cascade Biologics)达6个小时。PMA已显示出会引起很大程度的TNF-α分泌的增加,其在处理后的6小时达到峰值。培养后,收集细胞培养基,并使用R&D Systems(#DTA00C)的夹心酶联免疫吸附剂测定(ELISA)量化TNF-α的分泌。遵循所有生产厂家说明,将来自经处理的细胞的培养基与连接到微量滴定盘山的人TNF-α抗体一起进行培养。通过对比光密度单元与纯化TNF-α蛋白质的标准浓度,对TNF-α蛋白质进行量化。根据对照和处理样本之间的TNF-α蛋白质分泌量来计算其变化的百分比(%)。负值反映出测试化合物在已知会引起皮肤刺激(加入PMA)的条件下与未处理的对照相比降低TNF-α分泌物的能力。
基质金属蛋白酶活性(MMP3;MMP9)测定:活体外基质金属蛋白酶(MMP)抑制测定。MMP是细胞外蛋白酶,由于其具有广泛的基质特异性故在许多正常状态和疾病状态下具有重要的作用。MMP3基质包括胶原蛋白、纤维连接蛋白以及层粘连蛋白,而MMP9基质包括胶原蛋白VII、纤维连接蛋白以及层粘连蛋白。使用BioMol International用于MMP3(AK-400)和MMP-9(AK-410)的比色基质药物发现(Colorimetric Drug Discovery)试剂盒,该测定设计成使用含硫多肽作为发色体基质(Ac-PLG-[2-巯基-4-甲基-戊酰基]-LG-OC2H5)5,6)来测定MMP的蛋白酶活性。MMP剪切位点肽键被含硫多肽中的硫酯键代替。通过MMP对该键进行水解而生成氢硫基,其与DTNB[5,5’-二硫双(2-硝基苯甲酸),Ellman’s reagent]反应形成2-硝基-5-硫代苯甲酸,其在412nm(pH为6.0或大于7的ε=13,600M-1cm-1)的吸收度可被检测出。数值为纯化酶活性的抑制百分比。负值表示与稀释的对照相比,测试化合物抑制MMP活性的能力。
实施例3
组合物
在表5和6中对可包括芳香皮肤活性成份的本发明组合物的非限制性实施例进行了描述。
表5*
成分 | %浓度(重量) |
A相 | |
水 | 84.44 |
黄原胶 | 0.1 |
M-paraben | 0.15 |
P-paraben | 0.1 |
柠檬酸 | 0.01 |
B相 | |
鲸蜡醇 | 4.0 |
甘油硬脂酸 + PEG 100 | 4.0 |
棕榈酸盐 | 4.0 |
二甲聚硅氧烷 | 1.0 |
生育酚琥珀酸酯 | 0.2 |
C相** | |
芳香皮肤活性成份 | 2.0 |
*组合无制备过程:将黄原胶洒于水中并混合10分钟。随后,加入A相中的所有成份并加热至70-75℃。加入B相内的所有物质至另一个烧杯中并加热到70-75℃。将A相和B相在70-75℃的条件下混合。继续混合并使组合物冷却到30℃。随后,混合下加入C相的成份。
**本说明书中确认的芳香皮肤活性成份可并入到该组合物中。此外,这些成份的任何组合(包括2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30种或更多)均可加入到单一组合物中。在这种情况下,浓度范围可调节至期望值或所需值。
表6*
成分 | %浓度(重量) |
A相 | |
水 | 78.6 |
M-paraben | 0.2 |
P-paraben | 0.1 |
Na2EDTA | 0.1 |
乳木果油(Shea butter) | 4.5 |
矿脂 | 4.5 |
甘油 | 4.0 |
丙二醇 | 2.0 |
Finsolve TN | 2.0 |
B相 | |
Sepigel305 | 2.0 |
C相** | |
芳香皮肤活性成份 | 2.0 |
*加入A相内的物质到烧杯中并混合下加热到70-75℃。随后,将B相的
成份加入A相并在混合下冷却至30℃。随后,在混合下加入C相的成份。
**本说明书中确认的芳香皮肤活性成份可并入到该组合物中。
此外,这些成份的任何组合(包括2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30种或更多)均可加入到单一
组合物中。在这种情况下,浓度范围可调节至期望值或所需值。
实施例4
本发明组合物功效的确定
本发明组合物的功效可通过本领域普通技术人员所熟知的方法进行确定。下述的非限制性步骤可用于本发明中。还可以使用其它的测试过程,例如包括客观和主观的过程。
皮肤湿度/水合性的测量可用Nova Dermal Phase Meter进行阻抗测试来进行。阻抗计测量皮肤湿度含量的变化。皮肤的外层具有截然不同的电学性质。当皮肤干燥时其导电性非常差。当皮肤吸收水分后其导电性增加。因此,皮肤阻抗(与导电性相关)发生的变化可用于评估皮肤中水合性的变化。该单元可根据装置说明在每天的测试中进行校正。也可制作温度和相对湿度的标记。对测试对象的评价如下:在测试前,它们可在具有确定的湿度(如30-50%)和温度(如68-72℃)的一室中进行平衡。在脸部的每一边可单独读取三次阻抗值,并记录和计算平均值。可在阻抗计中使用T5设定来对在脸部每隔5秒所测得的阻抗值进行平均。阻抗值的变化可用统计学上的方差和有效值表示。
可使用Minolta Chromometer来评价皮肤清晰度以及雀斑和老年斑的减少。可对皮肤颜色的改变进行评价以确定由于使用Minolta Chroma Meter的a*值的产品处理而导致的潜在刺激。a*值用以测量红肿区域皮肤颜色的改变。这被用于确定组合物是否会引发刺激。这种测量可在面部的每一边进行并取平均值,作为左面部值和右面部值。皮肤的清晰度还可使用Minolta Meter进行测量。该测量值是Minolta Meter测得的a*,b和L值的组合并与皮肤亮度相关,同时还与皮肤光滑度和水合性密切相关。皮肤的读数如上所测。在一个非限制性方面,皮肤清晰度可描述为L/C,其中C为色度并定义为(a2+b2)1/2。
皮肤干燥度、表面细纹、皮肤光滑度以及肤色均可用临床评分技术进行评定。例如,皮肤干燥度的临床评分可采用5点标准的Kligman等级确定。(0)皮肤柔软且湿润;(1)皮肤表现正常,没有可视的干燥痕迹;(2)皮肤触摸时感觉轻微干燥但没有可视的片状剥落物;(3)皮肤感觉干燥、粗糙且具有白色的鳞状物;且(4)皮肤感觉非常干燥、粗糙且具有白色的鳞状物。可由两个临床医生独立地进行评价并取结果的平均。
肤色的临床评分可通过十点模拟数字刻度进行:(10)皮肤平整,带均匀的粉红棕色。使用手持显微镜检查时没发现黑色、黄疸或鳞状物。皮肤的微观肌理在触摸时非常均匀;(7)不使用放大镜时观察到均匀的肤色。无鳞状区域,但存在因色素沉着或红斑而引起的轻微的变色。变色区域的直径不超过1cm;(4)可以很容易观察到皮肤变色和不均匀的肌理。有轻微的鳞状物。在某些区域触摸皮肤时显得粗糙;且(1)肤色和皮肤肌理不均匀。存在多处鳞状物和变色区域,它们是色素减退、红斑或者黑斑。存在大面积的直径超过1cm的不均匀肤色。可由两个临床医生独立地进行评价并取结果的平均。
皮肤光滑度的临床评分通过十点模拟数字刻度进行分析。(10)光滑,皮肤湿润且有光泽,用手指轻抚表面时无阻力;(7)比较光滑,有轻微的阻力;(4)粗糙,有视觉上改变,揉搓时存在摩擦;以及(1)粗糙、有片状剥落物、表面不均匀。可由两个临床医生独立地进行评价并取结果的平均。
皮肤光滑度和皱纹的减少也可使用Packman等人(1978)公开的方法进行视觉上的评定。例如,在实验对象的每次访问时,可对每个实验对象浅脸部细线(SFL)的深浅程度和总数进行仔细评分并记录下来。通过将某一数字因子与深度/宽度/长度因子相乘得到一数字评分。获得眼部区域和嘴部区域(左边和右边)的评分并将二者相加得到总的皱纹评分。
使用Hargens冲击计测得皮肤紧绷度,这种装置通过将一个小物体落到皮肤上并记录该小物体首两次的反弹最高值以评价皮肤的弹性和紧绷性。该冲击计是一个小而轻的探测器,具有一相对钝的尖部(接触面积为4平方毫米)。该探针轻轻刺入皮肤,得到的测量结果取决于皮肤外层,包括皮肤的角质层和外表皮以及一些真皮层的性质。
皮肤的柔软性/柔顺性可使用含气电流计(Gas BearingElectrodynamometer)来评价,这种装置测量皮肤的应力/应变性质。皮肤的粘弹性与皮肤的潮湿程度相关。可用双面胶带将探针附着在皮肤表面来获得颊部区域上预先确定部位的测量值。可与皮肤表面平行地施加约3.5gm的力,并精确测量皮肤的位移。然后可计算出皮肤的柔顺性,并表达成DSR(动力弹簧刚性率,单位为gm/mm)。
皮肤上出现的线和皱纹可使用皮肤的复制品来进行评价。这些复制品是在皮肤表面压出的压痕。可使用类似硅胶的材料。可通过图像分析来对复制品进行分析。线和皱纹的可视性变化可通过取实验对象脸部的硅树脂复制品并用计算机图像分析系统分析复制品图像来进行客观地定量。复制品可取自眼部区域和颈部区域,并用以小角度入射光照射的数字相机来拍照。数字图像可用图像处理程序进行分析,并确定由皱纹或细线覆盖的复制品区域。
皮肤表面轮廓可采用轮廓曲线仪/记录针(Stylus)法来进行测量。这包括对复制品表面照射光或在其上拖动记录针。可通过远程传感器向计算机中输入记录针的垂直位移,且在对复制品的固定长度进行扫描后,可产生对皮肤轮廓的横截面分析的二维曲线。这可沿固定轴以重复任意次数产生皮肤的模拟三维图像。使用记录针技术可获得复制品的10个任意截面,将它们合并得到平均值。令人感兴趣的数值包括Ra,其为粗糙度(高度)的值的算术平均值,该值是通过将相对于平均轮廓高度的轮廓高度结合而计算出的值。Rt是最高峰和最低槽之间的垂直距离的最大值,Rz是平均峰宽减去平均峰高。这些值是经校正后的值,单位是mm。设备必须在每次使用前通过扫描已知值的金属标准进行标准化。Ra值可通过以下方程计算:Ra=标准粗糙度;lm=横贯(扫描)长度;以及y=相对于平均轮廓长度(x-轴)的轮廓位置的绝对值。
在另外的非限制性方面,本发明组合物的功效可使用皮肤类似物,例如MELANODERMTM进行评价。皮肤类似物细胞中的黑素细胞当暴露于L-二羟苯基丙胺酸这一黑色素的前体时将发生阳性染色。皮肤类似物MELANODERMTM可用各种不同的含本发明组合物和增白剂的碱处理,或单独用碱处理作为对照。或者,可用未处理的皮肤类似物样品作为对照。
芳香皮肤活性成分和组合物的氧化自由基吸收(或吸收度)能力(ORAC)也可通过测量这些成分或组合物的抗氧化活性来测定。该检测可用于对抑制已知的会导致细胞(如皮肤细胞)损伤的氧化剂如氧自由基所需的时间的程度和长度进行定量。芳香皮肤活性成分和组合物的ORAC值可通过本领域技术人员熟知的方法来确定(参见美国专利公开号2004/0109905和2005/0163880;Cao等(1993)),这些专利文献以引用的方式并入本申请)。总结,在Cao等(1993)描述的检测测量了抗氧化化合物在测试材料中抑制B-藻胆蛋白(B-PE)荧光度的减少的能力,这种减少是由过氧化氢自由基产生体AAPH所引起。
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本说明书中揭露的和要求保护的所有芳香皮肤活性成分、组合物、或方法均可在本公开基础上得以实施而无需进行过度实验。尽管本发明的芳香皮肤活性成分、组合物、或方法已经以具体的实施方式进行了描述,但在不脱离本发明的概念、精神和范围之内对芳香皮肤活性成分、组合物、或方法以及方法的步骤及步骤顺序作出改变对本领域技术人员将是显而易见的。
参考文献
以下参考文献所提供的补充这里所描述内容的示例性步骤或其它细节经引用而并入。
美国专利5,411,744
美国专利6,203,802
美国专利6,387,398
美国专利公开.2004/0109905
美国专利公开2005/0163880
Cao等,Free Radic.Biol.Med.,14:303-311,1993.
International Cosmetic Ingredient Dictionary,10th edition,2004.
Kreuter,J.Microencapsulation,5:115-127,1988.
Organic Chemistry,5th Ed.
Packman and Gams,J.Soc.Cos.Chem.,29:70-90,1978.
Remington's Pharmaceutical Sciences,18th Ed.Mack Printing Company,1289-1329,1990.
Claims (48)
1.一种治疗或预防皮肤病症的方法,该方法包括在皮肤上局部涂敷含芳香皮肤活性成份的组合物,其中该组合物的局部涂敷可治疗或预防皮肤病症。
2.权利要求1的方法,其中在皮肤上涂敷含药妆有效量的芳香皮肤活性成份。
3.权利要求1的方法,其中药妆有效量占组合物重量的0.005%~2.0%。
4.权利要求1的方法,其中芳香皮肤活性成份选自由以下物质组成的组:1,4-二氧杂环十七烷-5,17-二酮;(3E)-4-(2,6,6-三甲基-1-环已烯-1-基)-3-丁烯-2-酮;1-(1,2,3,4,5,6,7,8-八氢-2,3,8,8-四甲基-2-萘基)乙-1-酮;1-(2,3,8,8-四甲基-1,2,3,5,6,7,8,8a-八氢萘-2-基)乙酮;1-(2,3,8,8-四甲基-1,2,3,4,6,7,8,8a-八氢萘-2-基)乙酮;4-甲基-3-癸烯-5-醇;2,6-二甲基-5-庚烯醛;3,3-二甲基-5(2,2,3-三甲基-3-环戊烯-1-基)-4-戊烯-2-醇;3-己烯-1-醇(E)以及(Z);甲基3-氧代-2-戊基环戊烷羧酸酯;4-乙基-3,7-二甲基辛-1,6-二烯-3-醇;2-异丁基-4-甲基四氢-2H-吡喃-4-醇;α-甲基-1,3-苯并二噁茂-5-丙醛;5-庚基二氢呋喃-2(3H)-酮;3-(4-异丙基苯基)-2-甲基丙醛;2-甲基癸醛;2,4-壬二烯-1-醛;2-十二烯醛(E);2,6-壬二烯-1-醛(反式,反式;反式,顺式);1-十二醛;4-叔-丁基环己基乙酸酯;2-壬烯酸甲酯;1-甲基-3-(4-甲基戊-3-烯基)环己-3-烯甲醛;3a,4,5,6,7,7a-六氢-4,7-亚甲基-1h-茚-5(或6)-基醋酸酯;3-(4-乙苯基)-2,2-二甲基丙醛;3-(2-乙苯基)-2,2-二甲基丙醛;(Z)-4-甲基-3H-苯并[c][1,2]二氧杂环庚-3-酮;醋酸顺-2-己烯酯;(Z)-2-(丁-2-烯基)-3-甲基环戊-2-烯酮;甲基2,2-二甲基-6-甲基烯环己烷羧酸酯;(Z)-5-(羟基亚氨基)辛-3-酮;(2,4,6-)三甲基-3-环己烯-1-甲醛;(3,5,6-)三甲基-3-环己烯-1-甲醛;5-戊基二氢呋喃-2(3H)-酮;顺-6-壬烯醛;乙基3-异丙基二环[2.2.1]庚-5-烯-2-羧酸酯;以及3,7-二甲基-6-辛-1-基醋酸酯。
5.权利要求1的方法,其中该组合物包含至少两、三、四、五、六、或七种芳香皮肤活性成份。
6.权利要求1的方法,其中该组合物是乳液、面霜、洗液、溶液、无水基质、凝胶,或油膏。
7.一种用于降低皮肤细胞中脂氧酶活性的方法,该方法包括将皮肤细胞与芳香皮肤活性成份接触,其中将皮肤细胞与芳香皮肤活性成份接触以降低皮肤细胞中脂氧酶的活性。
8.权利要求7的方法,其中该皮肤细胞是选自由人的表皮角化细胞、人的真皮纤维原细胞和人的黑素细胞组成的组。
9.权利要求7的方法,其中该芳香皮肤活性成份选自由以下物质组成的组:1,4-二氧杂环十七烷-5,17-二酮;(3E)-4-(2,6,6-三甲基-1-环已烯-1-基)-3-丁烯-2-酮;1-(1,2,3,4,5,6,7,8-八氢-2,3,8,8-四甲基-2-萘基)乙-1-酮;1-(2,3,8,8-四甲基-1,2,3,5,6,7,8,8a-八氢萘-2-基)乙酮;1-(2,3,8,8-四甲基-1,2,3,4,6,7,8,8a-八氢萘-2-基)乙酮;4-甲基-3-癸烯-5-醇;2,6-二甲基-5-庚烯醛;3,3-二甲基-5(2,2,3-三甲基-3-环戊烯-1-基)-4-戊烯-2-醇;3-己烯-1-醇(E)以及(Z);甲基3-氧代-2-戊基环戊烷羧酸酯;4-乙基-3,7-二甲基辛-1,6-二烯-3-醇;2-异丁基-4-甲基四氢-2H-吡喃-4-醇;α-甲基-1,3-苯并二噁茂-5-丙醛;5-庚基二氢呋喃-2(3H)-酮;3-(4-异丙基苯基)-2-甲基丙醛;2-甲基癸醛;2,4-壬二烯-1-醛;2-十二烯醛(E);2,6-壬二烯-1-醛(反式,反式;反式,顺式);1-十二醛;4-叔-丁基环己基乙酸酯;2-壬烯酸甲酯;1-甲基-3-(4-甲基戊-3-烯基)环己-3-烯甲醛;3a,4,5,6,7,7a-六氢-4,7-亚甲基-1h-茚-5(或6)-基醋酸酯;3-(4-乙苯基)-2,2-二甲基丙醛;3-(2-乙苯基)-2,2-二甲基丙醛;(Z)-4-甲基-3H-苯并[c][1,2]二氧杂环庚-3-酮;醋酸顺-2-己烯酯;(Z)-2-(丁-2-烯基)-3-甲基环戊-2-烯酮;甲基2,2-二甲基-6-甲基烯环己烷羧酸酯;(Z)-5-(羟基亚氨基)辛-3-酮;(2,4,6-)三甲基-3-环己烯-1-甲醛;(3,5,6-)三甲基-3-环己烯-1-甲醛;5-戊基二氢呋喃-2(3H)-酮;顺-6-壬烯醛;乙基3-异丙基二环[2.2.1]庚-5-烯-2-羧酸酯;以及3,7-二甲基-6-辛-1-基醋酸酯。
10.权利要求7的方法,其中该皮肤细胞与至少两、三、四、五、六、或七种芳香皮肤活性成份接触。
11.权利要求7的方法,其中芳香皮肤活性成份被包含在一种组合物中。
12.权利要求11的方法,其中该组合物是乳液、面霜、洗液、溶液、无水基质、凝胶,或油膏。
13.一种用于降低皮肤细胞中环氧化酶活性的方法,该方法包括将皮肤细胞与芳香皮肤活性成份接触,其中将皮肤细胞与芳香皮肤活性成份接触以降低皮肤细胞中环氧化酶的活性。
14.权利要求13的方法,其中环氧化酶是环氧化酶-1或环氧化酶-2。
15.权利要求13的方法,其中皮肤细胞是选自由人的表皮角化细胞、人的真皮纤维原细胞和人的黑素细胞组成的组。
16.权利要求13的方法,其中芳香皮肤活性成份选自由以下物质组成的组:1,4-二氧杂环十七烷-5,17-二酮;(3E)-4-(2,6,6-三甲基-1-环已烯-1-基)-3-丁烯-2-酮;1-(1,2,3,4,5,6,7,8-八氢-2,3,8,8-四甲基-2-萘基)乙-1-酮;1-(2,3,8,8-四甲基-1,2,3,5,6,7,8,8a-八氢萘-2-基)乙酮;1-(2,3,8,8-四甲基-1,2,3,4,6,7,8,8a-八氢萘-2-基)乙酮;4-甲基-3-癸烯-5-醇;2,6-二甲基-5-庚烯醛;3,3-二甲基-5(2,2,3-三甲基-3-环戊烯-1-基)-4-戊烯-2-醇;3-己烯-1-醇(E)以及(Z);甲基3-氧代-2-戊基环戊烷羧酸酯;4-乙基-3,7-二甲基辛-1,6-二烯-3-醇;2-异丁基-4-甲基四氢-2H-吡喃-4-醇;α-甲基-1,3-苯并二噁茂-5-丙醛;5-庚基二氢呋喃-2(3H)-酮;3-(4-异丙基苯基)-2-甲基丙醛;2-甲基癸醛;2,4-壬二烯-1-醛;2-十二烯醛(E);2,6-壬二烯-1-醛(反式,反式;反式,顺式);1-十二醛;4-叔-丁基环己基乙酸酯;2-壬烯酸甲酯;1-甲基-3-(4-甲基戊-3-烯基)环己-3-烯甲醛;3a,4,5,6,7,7a-六氢-4,7-亚甲基-1h-茚-5(或6)-基醋酸酯;3-(4-乙苯基)-2,2-二甲基丙醛;3-(2-乙苯基)-2,2-二甲基丙醛;(Z)-4-甲基-3H-苯并[c][1,2]二氧杂环庚-3-酮;醋酸顺-2-己烯酯;(Z)-2-(丁-2-烯基)-3-甲基环戊-2-烯酮;甲基2,2-二甲基-6-甲基烯环己烷羧酸酯;(Z)-5-(羟基亚氨基)辛-3-酮;(2,4,6-)三甲基-3-环己烯-1-甲醛;(3,5,6-)三甲基-3-环己烯-1-甲醛;5-戊基二氢呋喃-2(3H)-酮;顺-6-壬烯醛;乙基3-异丙基二环[2.2.1]庚-5-烯-2-羧酸酯;以及3,7-二甲基-6-辛-1-基醋酸酯。
17.权利要求13的方法,其中该皮肤细胞与至少两、三、四、五、六、或七种芳香皮肤活性成份接触。
18.权利要求13的方法,其中芳香皮肤活性成份被包含在种一组合物中。
19.权利要求18的方法,其中该组合物是乳液、面霜、洗液、溶液、无水基质、凝胶,或油膏。
20.一种用于降低皮肤细胞中肿瘤坏死因子-α活性的方法,该方法包括将皮肤细胞与芳香皮肤活性成份接触,其中将皮肤细胞与芳香皮肤活性成份接触以降低皮肤细胞中肿瘤坏死因子-α的活性。
21.权利要求20的方法,其中皮肤细胞是选自由人的表皮角化细胞、人的真皮纤维原细胞和人的黑素细胞组成的组。
22.权利要求20的方法,其中芳香皮肤活性成份选自由以下物质组成的组:1,4-二氧杂环十七烷-5,17-二酮;(3E)-4-(2,6,6-三甲基-1-环已烯-1-基)-3-丁烯-2-酮;1-(1,2,3,4,5,6,7,8-八氢-2,3,8,8-四甲基-2-萘基)乙-1-酮;1-(2,3,8,8-四甲基-1,2,3,5,6,7,8,8a-八氢萘-2-基)乙酮;1-(2,3,8,8-四甲基-1,2,3,4,6,7,8,8a-八氢萘-2-基)乙酮;4-甲基-3-癸烯-5-醇;2,6-二甲基-5-庚烯醛;3,3-二甲基-5(2,2,3-三甲基-3-环戊烯-1-基)-4-戊烯-2-醇;3-己烯-1-醇(E)以及(Z);甲基3-氧代-2-戊基环戊烷羧酸酯;4-乙基-3,7-二甲基辛-1,6-二烯-3-醇;2-异丁基-4-甲基四氢-2H-吡喃-4-醇;α-甲基-1,3-苯并二噁茂-5-丙醛;5-庚基二氢呋喃-2(3H)-酮;3-(4-异丙基苯基)-2-甲基丙醛;2-甲基癸醛;2,4-壬二烯-1-醛;2-十二烯醛(E);2,6-壬二烯-1-醛(反式,反式;反式,顺式);1-十二醛;4-叔-丁基环己基乙酸酯;2-壬烯酸甲酯;1-甲基-3-(4-甲基戊-3-烯基)环己-3-烯甲醛;3a,4,5,6,7,7a-六氢-4,7-亚甲基-1h-茚-5(或6)-基醋酸酯;3-(4-乙苯基)-2,2-二甲基丙醛;3-(2-乙苯基)-2,2-二甲基丙醛;(Z)-4-甲基-3H-苯并[c][1,2]二氧杂环庚-3-酮;醋酸顺-2-己烯酯;(Z)-2-(丁-2-烯基)-3-甲基环戊-2-烯酮;甲基2,2-二甲基-6-甲基烯环己烷羧酸酯;(Z)-5-(羟基亚氨基)辛-3-酮;(2,4,6-)三甲基-3-环己烯-1-甲醛;(3,5,6-)三甲基-3-环己烯-1-甲醛;5-戊基二氢呋喃-2(3H)-酮;顺-6-壬烯醛;乙基3-异丙基二环[2.2.1]庚-5-烯-2-羧酸酯;以及3,7-二甲基-6-辛-1-基醋酸酯。
23.权利要求20的方法,其中该皮肤细胞与至少两、三、四、五、六、或七种芳香皮肤活性成份接触。
24.权利要求20的方法,其中芳香皮肤活性成份被包含在一种组合物中。
25.权利要求24的方法,其中该组合物是乳液、面霜、洗液、溶液、无水基质、凝胶,或油膏。
26.一种用于降低皮肤细胞中基质金属蛋白酶活性的方法,该方法包括将皮肤细胞与芳香皮肤活性成份接触,其中将皮肤细胞与芳香皮肤活性成份接触以降低皮肤细胞中基质金属蛋白酶的活性。
27.权利要求26的方法,其中基质金属蛋白酶是MMP3或MMP9。
28.权利要求26的方法,其中皮肤细胞是选自由人的表皮角化细胞、人的真皮纤维原细胞和人的黑素细胞组成的组。
29.权利要求26的方法,其中芳香皮肤活性成份选自由以下物质组成的组:1,4-二氧杂环十七烷-5,17-二酮;(3E)-4-(2,6,6-三甲基-1-环已烯-1-基)-3-丁烯-2-酮;1-(1,2,3,4,5,6,7,8-八氢-2,3,8,8-四甲基-2-萘基)乙-1-酮;1-(2,3,8,8-四甲基-1,2,3,5,6,7,8,8a-八氢萘-2-基)乙酮;1-(2,3,8,8-四甲基-1,2,3,4,6,7,8,8a-八氢萘-2-基)乙酮;4-甲基-3-癸烯-5-醇;2,6-二甲基-5-庚烯醛;3,3-二甲基-5(2,2,3-三甲基-3-环戊烯-1-基)-4-戊烯-2-醇;3-己烯-1-醇(E)以及(Z);甲基3-氧代-2-戊基环戊烷羧酸酯;4-乙基-3,7-二甲基辛-1,6-二烯-3-醇;2-异丁基-4-甲基四氢-2H-吡喃-4-醇;α-甲基-1,3-苯并二噁茂-5-丙醛;5-庚基二氢呋喃-2(3H)-酮;3-(4-异丙基苯基)-2-甲基丙醛;2-甲基癸醛;2,4-壬二烯-1-醛;2-十二烯醛(E);2,6-壬二烯-1-醛(反式,反式;反式,顺式);1-十二醛;4-叔-丁基环己基乙酸酯;2-壬烯酸甲酯;1-甲基-3-(4-甲基戊-3-烯基)环己-3-烯甲醛;3a,4,5,6,7,7a-六氢-4,7-亚甲基-1h-茚-5(或6)-基醋酸酯;3-(4-乙苯基)-2,2-二甲基丙醛;3-(2-乙苯基)-2,2-二甲基丙醛;(Z)-4-甲基-3H-苯并[c][1,2]二氧杂环庚-3-酮;醋酸顺-2-己烯酯;(Z)-2-(丁-2-烯基)-3-甲基环戊-2-烯酮;甲基2,2-二甲基-6-甲基烯环己烷羧酸酯;(Z)-5-(羟基亚氨基)辛-3-酮;(2,4,6-)三甲基-3-环己烯-1-甲醛;(3,5,6-)三甲基-3-环己烯-1-甲醛;5-戊基二氢呋喃-2(3H)-酮;顺-6-壬烯醛;乙基3-异丙基二环[2.2.1]庚-5-烯-2-羧酸酯;以及3,7-二甲基-6-辛-1-基醋酸酯。
30.权利要求26的方法,其中该皮肤细胞与至少两、三、四、五、六、或七种芳香皮肤活性成份接触。
31.权利要求26的方法,其中芳香皮肤活性成份被包含在一种组合物中。
32.权利要求31的方法,其中该组合物是乳液、面霜、洗液、溶液、无水基质、凝胶,或油膏。
33.一种用于降低皮肤细胞中氧化伤害的方法,该方法包括将皮肤细胞与芳香皮肤活性成份接触,其中将皮肤细胞与芳香皮肤活性成份接触以降低皮肤细胞中的氧化伤害。
34.权利要求33的方法,其中皮肤细胞是选自由人的表皮角化细胞、人的真皮纤维原细胞和人的黑素细胞组成的组。
35.权利要求33的方法,其中芳香皮肤活性成份选自由以下物质组成的组:1,4-二氧杂环十七烷-5,17-二酮;(3E)-4-(2,6,6-三甲基-1-环已烯-1-基)-3-丁烯-2-酮;1-(1,2,3,4,5,6,7,8-八氢-2,3,8,8-四甲基-2-萘基)乙-1-酮;1-(2,3,8,8-四甲基-1,2,3,5,6,7,8,8a-八氢萘-2-基)乙酮;1-(2,3,8,8-四甲基-1,2,3,4,6,7,8,8a-八氢萘-2-基)乙酮;4-甲基-3-癸烯-5-醇;2,6-二甲基-5-庚烯醛;3,3-二甲基-5(2,2,3-三甲基-3-环戊烯-1-基)-4-戊烯-2-醇;3-己烯-1-醇(E)以及(Z);甲基3-氧代-2-戊基环戊烷羧酸酯;4-乙基-3,7-二甲基辛-1,6-二烯-3-醇;2-异丁基-4-甲基四氢-2H-吡喃-4-醇;α-甲基-1,3-苯并二噁茂-5-丙醛;5-庚基二氢呋喃-2(3H)-酮;3-(4-异丙基苯基)-2-甲基丙醛;2-甲基癸醛;2,4-壬二烯-1-醛;2-十二烯醛(E);2,6-壬二烯-1-醛(反式,反式;反式,顺式);1-十二醛;4-叔-丁基环己基乙酸酯;2-壬烯酸甲酯;1-甲基-3-(4-甲基戊-3-烯基)环己-3-烯甲醛;3a,4,5,6,7,7a-六氢-4,7-亚甲基-1h-茚-5(或6)-基醋酸酯;3-(4-乙苯基)-2,2-二甲基丙醛;3-(2-乙苯基)-2,2-二甲基丙醛;(Z)-4-甲基-3H-苯并[c][1,2]二氧杂环庚-3-酮;醋酸顺-2-己烯酯;(Z)-2-(丁-2-烯基)-3-甲基环戊-2-烯酮;甲基2,2-二甲基-6-甲基烯环己烷羧酸酯;(Z)-5-(羟基亚氨基)辛-3-酮;(2,4,6-)三甲基-3-环己烯-1-甲醛;(3,5,6-)三甲基-3-环己烯-1-甲醛;5-戊基二氢呋喃-2(3H)-酮;顺-6-壬烯醛;乙基3-异丙基二环[2.2.1]庚-5-烯-2-羧酸酯;以及3,7-二甲基-6-辛-1-基醋酸酯。
36.权利要求33的方法,其中该皮肤细胞与至少两、三、四、五、六、或七种芳香皮肤活性成份接触。
37.权利要求33的方法,其中芳香皮肤活性成份被包含在一种组合物中。
38.权利要求37的方法,其中该组合物是乳液、面霜、洗液、溶液、无水基质、凝胶,或油膏。
39.一种局部皮肤护理组合物,该组合物包含有效量的芳香皮肤活性成份。
40.权利要求39的局部皮肤护理组合物,其中有效量是组合物重量的0.005%~2.0%。
41.权利要求39的局部皮肤护理组合物,其中该组合物是无香味的。
42.权利要求41的局部皮肤护理组合物,其中该组合物不包括另一种芳香化合物。
43.权利要求39的局部皮肤护理组合物,其中芳香皮肤活性成份选自由以下物质组成的组:1,4-二氧杂环十七烷-5,17-二酮;(3E)-4-(2,6,6-三甲基-1-环已烯-1-基)-3-丁烯-2-酮;1-(1,2,3,4,5,6,7,8-八氢-2,3,8,8-四甲基-2-萘基)乙-1-酮;1-(2,3,8,8-四甲基-1,2,3,5,6,7,8,8a-八氢萘-2-基)乙酮;1-(2,3,8,8-四甲基-1,2,3,4,6,7,8,8a-八氢萘-2-基)乙酮;4-甲基-3-癸烯-5-醇;2,6-二甲基-5-庚烯醛;3,3-二甲基-5(2,2,3-三甲基-3-环戊烯-1-基)-4-戊烯-2-醇;3-己烯-1-醇(E)以及(Z);甲基3-氧代-2-戊基环戊烷羧酸酯;4-乙基-3,7-二甲基辛-1,6-二烯-3-醇;2-异丁基-4-甲基四氢-2H-吡喃-4-醇;α-甲基-1,3-苯并二噁茂-5-丙醛;5-庚基二氢呋喃-2(3H)-酮;3-(4-异丙基苯基)-2-甲基丙醛;2-甲基癸醛;2,4-壬二烯-1-醛;2-十二烯醛(E);2,6-壬二烯-1-醛(反式,反式;反式,顺式);1-十二醛;4-叔-丁基环己基乙酸酯;2-壬烯酸甲酯;1-甲基-3-(4-甲基戊-3-烯基)环己-3-烯甲醛;3a,4,5,6,7,7a-六氢-4,7-亚甲基-1h-茚-5(或6)-基醋酸酯;3-(4-乙苯基)-2,2-二甲基丙醛;3-(2-乙苯基)-2,2-二甲基丙醛;(Z)-4-甲基-3H-苯并[c][1,2]二氧杂环庚-3-酮;醋酸顺-2-己烯酯;(Z)-2-(丁-2-烯基)-3-甲基环戊-2-烯酮;甲基2,2-二甲基-6-甲基烯环己烷羧酸酯;(Z)-5-(羟基亚氨基)辛-3-酮;(2,4,6-)三甲基-3-环己烯-1-甲醛;(3,5,6-)三甲基-3-环己烯-1-甲醛;5-戊基二氢呋喃-2(3H)-酮;顺-6-壬烯醛;乙基3-异丙基二环[2.2.1]庚-5-烯-2-羧酸酯;以及3,7-二甲基-6-辛-1-基醋酸酯。
44.权利要求39的局部皮肤护理组合物,其中该组合物包含至少两、三、四、五、六、或七种芳香皮肤活性成份。
45.权利要求39的局部皮肤护理组合物,其中该组合物是乳液、面霜、洗液、溶液、无水基质、凝胶,或油膏。
46.权利要求39的局部皮肤护理组合物,其中该组合物不包括另一种皮肤活性成分。
47.权利要求46的局部皮肤护理组合物,其中该组合物不包括另一种芳香化合物。
48.权利要求47的局部皮肤护理组合物,其中该组合物是无香味的。
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US20170000713A1 (en) * | 2015-06-30 | 2017-01-05 | The Gillette Company | Personal care compositions comprising a sensate |
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