CN107028808A - 局部用组合物 - Google Patents
局部用组合物 Download PDFInfo
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- CN107028808A CN107028808A CN201611242543.XA CN201611242543A CN107028808A CN 107028808 A CN107028808 A CN 107028808A CN 201611242543 A CN201611242543 A CN 201611242543A CN 107028808 A CN107028808 A CN 107028808A
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Abstract
本发明一般涉及对使皮肤和/或毛发清洁、去角质、光滑、滋润、水合和/或改善外观和/或状态有益的方法和组合物,其使用包含牛油果脂、PEG‑50牛油果脂和/或水合硅石的组合物。
Description
技术领域
相关申请的交叉引用
本申请要求2015年12月30日提交的美国临时申请62/273011号的权益,其内容通过引用并入本申请中。
本发明一般涉及能够用于改善皮肤状态和/或视觉外观的组合物。在某些方面,本发明的组合物可以包含例如使皮肤和/或毛发清洁、去角质、光滑、滋润、水合和/或软化的成分的组合。在其他方面,该成分的组合可以对干燥皮肤提供迅速缓解和/或舒缓,应用于皮肤后迅速吸收和/或没有残留。这种成分的组合可以包含在广泛的产品制剂中(例如霜剂、洗面奶等)。
背景技术
衰老、长期暴露于不利环境因素、营养失调、疲劳等会以被认为视觉上不期望的方式改变皮肤的视觉外观、物理性能或生理功能。最显著和明显的改变包括产生细纹和皱纹、损失弹性、下垂增加、损失紧实度、损失颜色均匀性或色调、粗糙的表面纹理和斑点色素沉淀。随着皮肤老化或经历长期环境损害而发生的稍不明显但可测量的改变包括细胞和组织活性普遍降低、细胞复制速率降低、皮肤血流减少、含水量降低、累积的结构和功能错误、普通生化过程正常调节的变化以及皮肤改造和自我修复能力的降低。皮肤外观和功能的许多变化由皮肤外表皮层改变导致,而其他变化由下面真皮的改变导致。
利用已知皮肤活性成分改善皮肤视觉外观的先前尝试显示具有各种缺点,例如皮肤刺激和较长恢复期。
保持皮肤和/或毛发水分有助于克服皮肤和毛发中的不期望改变。然而,保持皮肤水分会是困难的。对于具有比普通皮肤更干燥皮肤(干燥皮肤类型)的受试者尤其如此。暴露于化学品、溶剂、化妆水、化妆品、纺织品或干燥环境是可以使皮肤失去水分的许多方式中的一些。
清洁和/或洁净皮肤和头发的结果是皮肤和毛发可以失去水分。皮肤和毛发清洁和/或洁净组合物通常用于皮肤和/或毛发,用水冲洗掉(例如洗去型产品)、夺取皮肤的天然油和脂质。进一步地,清洁和洁净组合物常常含有会使待清洁表面腐蚀的成分。例如,许多种洗面奶和爽肤水使用可以引起皮肤刺激的一些表面活性剂。
滋润剂是特别设计为使皮肤外层(表皮)更柔软和更柔韧的化学剂复合混合物。其通过减少蒸发而增加皮肤水合作用(水含量)。天然存在的皮肤脂质和甾醇,以及人造的或天然的油、滋润剂、润肤剂、润滑剂等可以是商业化皮肤滋润剂组合物的一部分。其通常作为可用于化妆品或治疗用途的商业产品,但是也可以使用通常药学成分在家制成。然而,滋润剂并不完美。与滋润剂相关的一些问题包括不愉快的触觉特性(例如厚重、油腻或粘稠的感觉)、不稳定、皮肤刺激性或滋润能力不足。
发明内容
本发明人确定了具有治疗效果的化合物组合和的组合物。具体地,发明人确认了成分的组合,其包含牛油果脂、PEG-50牛油果脂和/或水合硅石,其发挥使皮肤和/或毛发清洁、去角质、光滑、滋润、水合和/或改善外观和/或状态的作用。在其他方面,成分的组合可以对干燥皮肤提供迅速缓解和/或舒缓,应用至皮肤后迅速吸收和/或没有残留。
在一个实例中,公开了能够使皮肤去角质的局部用组合物。在一个实例中,上述局部用组合物包含水合硅石、水、月桂酰硫酸酯TEA盐和椰油酰胺丙基甜菜碱中的任一种、任意组合或全部。组合物内的成分量可以改变(例如,该量以重量百分比计可以低如0.000001%,高如90%,或是其间任意范围)。在一个实例中,组合物包含1重量%至10重量%的水合硅石、60重量%至90重量%的水、5重量%至15重量%的月桂酰硫酸酯TEA盐和0.5重量%至3重量%的椰油酰胺丙基甜菜碱。组合物还可以包含一种或更多种本文所描述的成分。例如,组合物可以包含选自一种或更多种调理剂、滋润剂、pH调节剂、结构化剂、无机盐和防腐剂的一种或更多种附加成分。
在一些方面,组合物还包含丙烯酸酯共聚物、氯化钠和羟乙基纤维素。在一些方面,组合物包含0.1重量%至5重量%的丙烯酸酯共聚物、0.1重量%至5重量%的氯化钠和0.1重量%至1.5重量%的羟乙基纤维素。在一些方面,组合物还包含三乙醇胺、丙二醇、氢化霍霍巴油、对羟基苯甲酸甲酯和EDTA二钠。在一些方面,组合物包含0.5重量%至3重量%的三乙醇胺、0.1重量%至3重量%的丙二醇、0.1重量%至3重量%的氢化霍霍巴油、0.01重量%至1重量%的对羟基苯甲酸甲酯和0.01重量%至1重量%的EDTA二钠。在一些方面,组合物还包含柠檬酸。在一些方面,组合物包含0.1重量%至1重量%的柠檬酸。在一些方面,组合物还包含杏(Prunus armeniaca)籽粉和桃(Prunus persica)籽粉。在一些方面,组合物包含0.01重量%至1重量%的杏籽粉和0.01重量%至1重量%的桃籽粉。在一些方面,组合物还包含刺梨提取物。在一些方面,组合物包含0.0001重量%至1重量%的刺梨提取物。
还公开了上述组合物的使用方法。在一个方面,通过将上述组合物中的任一种应用至皮肤将公开的组合物用于使皮肤去角质,其中使皮肤去角质。在一些方面,通过将上述组合物中的任一种应用至皮肤将公开的组合物用于清洁皮肤,其中使皮肤清洁。在一些方面,通过将上述组合物中的任一种应用至皮肤将公开组合物用于使皮肤光滑,其中使皮肤光滑。在一些方面,在应用后将组合物留在皮肤和/或毛发上。在一些方面,在应用后将组合物从皮肤和/或毛发洗去。
在另一个实例中,公开了能够使皮肤去角质的局部用组合物。在一个实例中,上述局部用组合物包含水合硅石、水、月桂酰硫酸酯TEA盐、椰油酰胺丙基甜菜碱和PEG-50牛油果脂中的任一种、任意组合或全部。组合物内的成分量可以改变(例如,该量以重量百分比计可以低如0.000001%,高如90%,或是其间的任意范围)。在一个实例中,组合物包含0.1重量%至5重量%的PEG-50牛油果脂。组合物还包含本文公开的一种或更多种成分。例如,组合物可以包含选自一种或更多种调理剂、滋润剂、pH调节剂、结构化剂、无机盐和防腐剂的另外的成分中的一种或更多种。
在一些方面,组合物还包含三乙醇胺和丙烯酸酯/C10-30丙烯酸烷基酯交联聚合物。在一些方面,组合物包含0.1重量%至3重量%的三乙醇胺和0.1重量%至3重量%的丙烯酸酯/C10-30丙烯酸烷基酯交联聚合物。在一些方面,组合物还包含苯氧乙醇、辛甘醇、氯化钠、EDTA二钠、乙基己基甘油和己二醇。在一些方面,组合物包含0.1重量%至1.5重量%的三乙醇胺、0.1重量%至1重量%的辛甘醇、0.01重量%至1重量%的氯化钠、0.01重量%至1重量%的EDTA二钠、0.01重量%至1重量%的乙基己基甘油和0.01重量%至1重量%的己二醇。在一些方面,组合物还包含氢化霍霍巴油。在一些方面,组合物包含0.1重量%至1重量%的氢化霍霍巴油。在一些方面,组合物还包含聚山梨醇酯20和硬脂醇硬脂酸酯。在一些方面,组合物包含0.1重量%至3重量%的聚山梨醇酯20和0.01重量%至1重量%的硬脂醇硬脂酸酯。在一些方面,组合物还包含刺梨提取物。在一些方面,组合物包含0.0001重量%至1重量%的刺梨提取物。
还公开了上述组合物的使用方法。在一个方面,通过将上述组合物中的任一种应用至皮肤上,公开的组合物用于使皮肤去角质,其中使皮肤去角质。在一些方面,通过将上述组合物中的任一种应用至皮肤,公开的组合物被用于清洁皮肤,其中使皮肤清洁。在一些方面,通过将上述组合物中的任一种应用至皮肤,公开组合物被用于使皮肤光滑,其中使皮肤光滑。在一些方面,将组合物在应用后留在皮肤和/或毛发上。在一些方面,将组合物在应用后从皮肤和/或毛发洗去。
在另一个实例中公开了能够使皮肤和/或毛发滋润的局部用组合物。在一个实例中,上述局部用组合物包含牛油果(Butyrospermum parkii)脂、水、鲸蜡硬脂醇、甘油硬脂酸酯、聚丙烯酸酯-13、聚异丁烯和聚山梨醇酯20。组合物内的成分量可以改变(例如,该量以重量百分比计可以低如0.000001%,高如90%,或是其间任意范围)。在一个实例中,组合物包含0.1重量%至10重量%的牛油果脂、65重量%至85重量%的水、1重量%至10重量%的鲸蜡硬脂醇、1重量%至10重量%的甘油硬脂酸酯、0.01重量%至1重量%的聚丙烯酸酯-13、0.01重量%至1重量%的聚异丁烯、0.001重量%至0.1重量%的聚山梨醇酯20。组合物还可以包含本文描述的一种或更多种成分。例如,组合物可以包含选自一种或更多种调理剂、滋润剂、pH调节剂、结构化剂、无机盐和防腐剂的一种或更多种附加成分。
在一些方面,组合物还包含甘油、丙二醇、葵花(Helianthus annuus)籽油和红花(Carthamus tinctorius)籽油。在一些方面,组合物包含1重量%至10重量%的甘油、0.5重量%至5重量%的丙二醇、0.5重量%至5重量%的葵花籽油和0.1重量%至3重量%的红花籽油。在一些方面,组合物还包含PEG-100硬脂酸酯、苯氧乙醇、丙二醇、杏仁油、聚二甲基硅氧烷、辛甘醇、醋酸生育酚、黄原胶、EDTA二钠和乙基己基甘油。在一些方面,组合物包含0.1重量%至3重量%的PEG-100硬脂酸酯、0.1重量%至3重量%的苯氧乙醇、0.1重量%至3重量%的丙二醇、0.1重量%至3重量%的杏仁油、0.1重量%至1.5重量%的聚二甲基硅氧烷、0.1重量%至1.5重量%的辛甘醇、0.1重量%至1.5重量%的醋酸生育酚、0.01重量%至1重量%的黄原胶、0.01重量%至1重量%的EDTA二钠和0.01重量%至1重量%的乙基己基甘油。在一些方面,组合物被配制成乳液。在一些方面,组合物被配制为霜。
还公开了上述组合物的使用方法。在一个方面,通过将上述组合物中的任一种应用至皮肤和/或毛发上,将公开的组合物用于使皮肤滋润,其中使皮肤和/或毛发滋润。在一些方面,通过将上述组合物中的任一种应用至皮肤上,公开的组合物用于舒缓干燥皮肤,其中使皮肤舒缓。在一些方面,通过将上述组合物中的任一种应用至皮肤,将公开的组合物用于软化皮肤,其中使皮肤软化。在一些方面,通过将上述组合物中的任一种应用至皮肤,将公开组合物用于使皮肤光滑,其中使皮肤光滑。在一些方面,在应用后将组合物留在皮肤和/或毛发上。在一些方面,在应用后将组合物从皮肤和/或毛发洗去。
在具体的方面,本发明的组合物被配制为局部用皮肤组合物。组合物可以含有用于化合物、组合物和提取物的皮肤学上可接受的载剂或载体。组合物还可以包含滋润剂或滋润剂、表面活性剂、含有机硅的化合物、UV剂、油和或本说明书所确定的其他成分或本领域已知的成分。组合物可以是露、霜、凝胶、精华液、乳液(例如水包油、油包水、水包有机硅、有机硅包水、水包油包水、油包水包油、有机硅包水包油等)、溶液(例如水溶液或水醇溶液)、无水基质(例如口红或粉末)、软膏、奶、贴膏、气雾剂、固体形式、眼啫喱等。组合物可以是粉末形式的(例如干燥的、冻干的、微粒的等)。组合物可以配制用于在使用期间每天局部皮肤施用至少1次、2次、3次、4次、5次、6次、7次或更多次。在本发明的其它方面中,该组合物可以是储存稳定或颜色稳定的或两者。还期望可以选择组合物的黏度以达到所期望结果,例如根据所期望组合物类型,该组合物的黏度可以为约1cps至远超过1百万cps或者其中可得到的任意范围或整数(例如,在25℃用TC轴以2.5rpm在布氏黏度计上测量的,2cps、3cps、4cps、5cps、6cps、7cps、8cps、9cps、10cps、20cps、30cps、40cps、50cps、60cps、70cps、80cps、90cps、100cps、200cps、300cps、400cps、500cps、600cps、700cps、800cps、900cps、1000cps、2000cps、3000cps、4000cps、5000cps、6000cps、7000cps、8000cps、9000cps、10000cps、20000cps、30000cps、40000cps、50000cps、60000cps、70000cps、80000cps、90000cps、100000cps、200000cps、300000cps、400000cps、500000cps、600000cps、700000cps、800000cps、900000cps、1000000cps、2000000cps、3000000cps、4000000cps、5000000cps、10000000cps等)。
还可以将本发明的组合物改性以具有所期望的氧自由基吸收能力(ORAC)值。在某些非限制性方面,可以将本说明书全文中所确定的本发明的组合物或其成分或提取物改性以具有每毫克至少约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或更多或其中可得到的任意范围的ORAC值。
在非限制性方面的该组合物可以具有约6至约9的pH。在其它方面,pH可以是1、2、3、4、5、6、7、8、9、10、11、12、13或14。组合物可以包含甘油三酸酯。非限制性实例包括小链甘油三酸酯、中链甘油三酸酯和大链甘油三酸酯。在某些方面,甘油三酸酯是中链甘油三酸酯(例如辛酸癸酸甘油三酯)。组合物还可以包含防腐剂。防腐剂的非限制性实例包括对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、或对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的混合物。
本发明的组合物可以具有UVA和UVB吸收性质。该组合物可以具有2、3、4、5、6、7、8、9、10、11、12、13、14、15、20、25、30、35、40、45、50、55、60或更大或其中得到的任何整数的防晒指数(SPF)。该组合物可以是防晒露、防晒喷雾或防晒霜。
本发明的组合物还可以包含以下附加成分中的任何一种、任意组合或全部:水、螯合剂、滋润剂、防腐剂、增稠剂、含有机硅的化合物、精油、结构化剂、维生素、药物成分或抗氧化剂,或这类成分的任意组合或这类成分的混合物。在某些方面,该组合物可以包含在之前句子中确定的这些附加成分中的至少2种、3种、4种、5种、6种、7种、8种、9种、10种或全部。这些附加成分的非限制性实例在本说明书全文确定并通过引用并入本章节。这类成分量以组合物重量或体积计可以为0.0001%至99.9%,或如本说明书其它章节中所公开的范围之间的任何整数或范围,其通过引用并入本段。
还预期了包含本发明组合物的试剂盒。在某些实施方案中,该组合物包含在容器中。该容器可以是瓶子、分配器或包装。该容器可以分配组合物的预定量。在某些方面,该组合物以喷雾、薄雾、团块或液体分配。该容器可以在其表面上包含标记。该标记可以是单词、缩写、图片或符号。
还预期的是本说明书通篇所公开的组合物可以用作免洗型或洗去型组合物。举例来说,免洗型组合物可以是局部施用至皮肤并在皮肤上保留一段时间(例如,至少5分钟、6分钟、7分钟、8分钟、9分钟、10分钟、20分钟或30分钟,或至少1小时、2小时、3小时、4小时、5小时、6小时、7小时、8小时、9小时、10小时、11小时、12小时、13小时、14小时、15小时、16小时、17小时、18小时、19小时、20小时、21小时、22小时、23小时或24小时,或整晚或整天)的组合物。或者,洗去型组合物可以是旨在施用于皮肤然后在一段时间内如小于5分钟、4分钟、3分钟、2分钟或1分钟从皮肤移除或洗去(比如用水)的产品。洗去型组合物的实例可以是洗面奶、洗发水、护发素或肥皂。免洗型组合物的实例可以是皮肤滋润剂、防晒剂、面膜、晚霜或日霜。
预期对于本发明的任何方法或组合物,可以实施本说明书中所讨论的任何实施方案,反之亦然。此外,本发明的组合物可以用于实现本发明的方法。
在一个实施方案中,本发明的组合物可以是可药用的或可化妆用的,或可以具有舒适的触觉性质。“可药用的”、“可化妆用的”和/或“舒适的触觉性质”描述具有令皮肤感觉舒适的特定触觉性质的组合物(例如,不是太稀或太油的组合物、具有丝滑质地的组合物、非粘性或粘性的组合物等。)。可药用的或可化妆用的还可以涉及组合物的乳脂状或润滑性能,或组合物的水分保留性能。
还预期了包含本发明组合物的产品。在非限制性方面,该产品可以是化妆品。该化妆品可以是本说明书其它章节所述的那些化妆品,或是本领域技术人员已知的那些化妆品。产品的非限制性实例包括润肤剂、霜、露、柔肤水、凝胶、化妆水、粉底、晚霜、口红、洗面奶、爽肤水、防晒剂、面膜、抗老化产品、除臭剂、止汗剂、香水、古龙水等。
还公开了本发明的以下实施方案1至37。实施方案1是局部用组合物,其包含水合硅石、水、月桂酰硫酸酯TEA盐和椰油酰胺丙基甜菜碱,其中所述组合物能够使皮肤去角质。实施方案2是实施方案1的局部用组合物,其包含1重量%至10重量%的水合硅石、60重量%至90重量%的水、5重量%至15重量%的月桂醇硫酸酯TEA盐和0.5重量%至3重量%的椰油酰胺丙基甜菜碱。实施方案3是实施方案1至2中任一项的局部用组合物,其还包含丙烯酸酯共聚物、氯化钠和羟乙基纤维素。实施方案4是实施方案3的局部用组合物,其包含0.1重量%至5重量%的丙烯酸酯共聚物、0.1重量%至5重量%的氯化钠和0.1重量%至1.5重量%的羟乙基纤维素。实施方案5是实施方案1至4中任一项的局部用组合物,其还包含三乙醇胺、丙二醇、氢化霍霍巴油、对羟基苯甲酸甲酯和EDTA二钠。实施方案6是实施方案5的局部用组合物,其包含0.5重量%至3重量%的三乙醇胺、0.1重量%至3重量%的丙二醇、0.1重量%至3重量%的氢化霍霍巴油、0.01重量%至1重量%的对羟基苯甲酸甲酯和0.01重量%至1重量%的EDTA二钠。实施方案7是实施方案1至6中任一项的局部用组合物,其还包含柠檬酸。实施方案8是实施方案7的局部用组合物,其包含0.1重量%至1重量%的柠檬酸。实施方案9是实施方案1至8中任一项的局部用组合物,其还包含杏籽粉和桃籽粉。实施方案10是实施方案9的局部用组合物,其包含0.01重量%至1重量%的杏籽粉和0.01重量%至1重量%的碧桃籽粉。实施方案11是实施方案1的局部用组合物,其还包含PEG-50牛油果脂。实施方案12是实施方案11的局部用组合物,其包含0.1重量%至5重量%的PEG-50牛油果脂。实施方案13是实施方案11至12中任一项的局部用组合物,其还包含三乙醇胺和丙烯酸酯/C10-30丙烯酸酯烷基交联聚合物。实施方案14是实施方案13的局部用组合物,其包含0.1重量%至3重量%的三乙醇胺和0.1重量%至3重量%的丙烯酸酯/C10-30丙烯酸烷基酯交联聚合物。实施方案15是实施方案11至14中任一项的局部用组合物,其还包含苯氧乙醇、辛甘醇、氯化钠、EDTA二钠、乙基己基甘油和己二醇。实施方案16是实施方案15的局部用组合物,其包含0.1重量%至1.5重量%的苯氧乙醇、0.1重量%至1重量%的辛甘醇、0.01重量%至1重量%的氯化钠、0.01重量%至1重量%的EDTA二钠、0.01重量%至1重量%的乙基己基甘油和0.01重量%至1重量%的己二醇。实施方案17是实施方案11至16中任一项的局部用组合物,其还包含氢化霍霍巴油。实施方案18是实施方案17的局部用组合物,其包含0.1重量%至1重量%的氢化霍霍巴油。实施方案19是实施方案11至16中任一项的局部用组合物,其还包含聚山梨醇酯20和硬脂醇硬脂酸酯。实施方案20是实施方案19的局部用组合物,其包含0.1重量%至3重量%的聚山梨醇酯20和0.01重量%至1重量%的硬脂醇硬脂酸酯。实施方案21是实施方案1至20中任一项的局部用组合物,其还包含刺梨提取物。实施方案22是实施方案21的局部用组合物,其包含0.0001重量%至1重量%的刺梨提取物。实施方案23是局部用组合物,其包含牛油果脂、水、鲸蜡硬脂醇、硬脂酸甘油酯、聚丙烯酸酯-13、聚异丁烯和聚山梨醇酯20,其中组合物能够使皮肤和/或毛发滋润。实施方案24是实施方案23的局部用组合物,其包含0.1重量%至10重量%的牛油果脂、60重量%至85重量%的水、1重量%至10重量%的鲸蜡硬脂醇、1重量%至10重量%的硬脂酸甘油酯、0.01重量%至1重量%的聚丙烯酸酯-13、0.01重量%至1重量%的聚异丁烯和0.001重量%至0.1重量%的聚山梨醇酯20。实施方案25是实施方案23至24中任一项的局部用组合物,其还包含甘油、丙二醇、葵花籽油和红花籽油。实施方案26是实施方案25的局部用组合物,其包含1重量%至10重量%的甘油、0.5重量%至5重量%的丙二醇、0.5重量%至5重量%的葵花籽油和0.1重量%至3重量%的红花籽油。实施方案27是实施方案23至26中任一项的局部用组合物,其还包含PEG-100硬脂酸酯、苯氧乙醇、丙二醇、杏仁油、聚二甲基硅氧烷、辛甘醇、醋酸生育酚、黄原胶、EDTA二钠和乙基己基甘油。实施方案28是实施方案27的局部用组合物,其包含0.1重量%至3重量%的PEG-100硬脂酸酯、0.1重量%至3重量%的苯氧乙醇、0.1重量%至3重量%的丙二醇、0.1重量%至3重量%的杏仁油、0.1重量%至1.5重量%的聚二甲基硅氧烷、0.1重量%至1.5重量%的辛甘醇、0.1重量%至1.5重量%的醋酸生育酚、0.01重量%至1重量%的黄原胶、0.01重量%至1重量%的EDTA二钠和0.01重量%至1重量%的乙基己基甘油。实施方案29是实施方案23至28中任一项的局部用组合物,其中组合物被配制为乳液。实施方案30是实施方案29的局部用组合物,其中组合物是霜。实施方案31是使皮肤去角质的方法,其包括将实施方案1至22中任一项的组合物应用至皮肤,其中使皮肤去角质。实施方案32是清洁皮肤的方法,其包括将实施方案1至22中任一项的组合物应用至皮肤,其中使皮肤清洁。实施方案33是使皮肤光滑的方法,其包括将实施方案1至22中任一项的组合物应用至皮肤,其中使皮肤光滑。实施方案34是使皮肤和/或毛发滋润的方法,其包括将实施方案23至30中任一项的组合物应用至皮肤和/或毛发,其中使皮肤和/或毛发滋润。实施方案35是使皮肤舒缓的方法,其包括将实施方案23至30中任一项的组合物应用至皮肤,其中使皮肤舒缓。实施方案36是使皮肤软化的方法,其包括将实施方案23至30中任一项的组合物应用至皮肤,其中使皮肤软化。实施方案37是使皮肤光滑的方法,其包括将实施方案23至30中任一项的组合物应用至皮肤,其中使皮肤光滑。
“局部施用”指施用或涂敷组合物到嘴唇或角质组织表面上。“局部皮肤用组合物”包括适合在皮肤和/或角质组织局部施用的组合物。这类组合物一般为皮肤病学上可接受的,这是因为当施用到皮肤和/或角质组织时,其不具有异常毒性、不相容性、不稳定性、过敏反应等。本发明的局部护肤组合物可以具有选定的黏度以避免施用到皮肤和/或角质组织后明显的滴落或淤积。
“角质组织”包括设为哺乳动物最外保护层的含角质层,包含但不限于嘴唇、皮肤、毛发和指甲。
术语“大约”或“约”定义为如本领域普通技术人员所理解的接近于,并且在一个非限制性实施方案中该术语定义为在10%以内,优选在5%以内,更优选在1%以内,最优选在0.5%以内。
术语“基本上”及其变体定义为如本领域普通技术人员所理解的大部分但不必全部地为指定的事物,并且在一个非限定性实施方案中基本上涉及的范围在10%以内、在5%以内、在1%以内或在0.5%以内。
术语“抑制”或“减少”或这些术语的任何变体包括为了实现所期望结果,任何可测量的减少或完全的抑制。术语“促进”或“增加”或这些术语的任何变体包含为了实现所期望结果,蛋白质或分子(例如基体蛋白,例如纤连蛋白、层粘连蛋白、胶原蛋白或弹性蛋白,或分子例如透明质酸)的任何可测量增加或产生。
作为本说明书和/或权利要求所使用的术语,术语“有效的”表示足够实现所期望的、所希望的或所预期的结果。
当在权利要求和/或说明书中与术语“包含”一起使用时,要素前面不使用数量词可以表示“一个”,但是其也符合“一个或更多个”、“至少一个”和“一个或多于一个”的意思。
如本说明书和权利要求所使用的,单词“包含”、“具有”、“包括”或“含有”是包括性的或开放式的,并且不排除附加的、未列举的要素或方法步骤。
组合物及其使用方法可以“包含”本说明书通篇所公开的成分或步骤的任一个、“主要由其组成”或“由其组成”。如本文所列举的,“基本由其组成”表示在组合物中包含附加成分不实质上影响前述成分组合的性质。一个这样的实例会是包含对所述组合或对全部例如组合物的作用(使皮肤平滑的能力)确定的任一种成分有不利影响(例如降低功效或稳定性)的成分。
本发明的其它目的、特征和优点通过以下详细描述会变得明显。然而,应理解详细描述和实施例在表明本发明具体实施方案时仅以举例说明给出。另外,期望通过该详细描述,本发明的精神和范围内的变化和修改对于本领域技术人员会变得明显。
具体实施方式
如上所述,本发明的几个独特方面是成分的组合,成分包含牛油果脂、PEG-50牛油果脂和/或水合硅石。这允许发挥清洁、去角质、光滑、滋润、水合、软化和/或改善皮肤和/或毛发的外观和/或状态的组合物的益处。在其他方面,成分的组合可以对干燥皮肤提供迅速缓解和/或舒缓,应用于皮肤后迅速吸收和/或没有残留。
以下分段更详细地描述本发明的非限制性方面。
将本发明的具体组合物设计为作为清洁组合物。组合物依赖于PEG-50牛油果脂和水合硅石中任一种或全部的独特组合。实施例1、表1和2中提供了这种组合物的实例。将本发明的具体组合物设计为作为霜组合物。组合物依赖于包含牛油果脂的成分的独特组合。实施例1和表3中提供了这种组合物的实例。
可以将以上组合物应用至皮肤或毛发、洗去或保留在皮肤或毛发上一段时间(例如至少1分钟、2分钟、3分钟、4分钟、5分钟、10分钟、20分钟、30分钟或60分钟或更长)。在一些实例中,在保留在皮肤上之后,如果需要,组合物可以从皮肤上洗去或从皮肤上剥离。在某些方面,在应用后将组合物从皮肤和/或毛发上洗去。
A.活性成分
本发明的前提是确定以下活性成分的组合—牛油果脂、PEG-50牛油果脂和/或水合硅石—可以用于改善皮肤的视觉外观,清洁、去角质、光滑、滋润、水合、软化和/或改善皮肤和/或毛发的外观和/或状态。在其他方面,成分的组合可以对干燥皮肤提供迅速缓解和/或舒缓,应用于皮肤后迅速吸收和/或没有残留。
附加活性成分也可以与上述活性成分组合使用。在一个方面,活性成分包含牛油果脂、PEG-50牛油果脂和/或水合硅石中的一种或更多种。在下文中更详细地讨论这些成分。
牛油果脂是从非洲牛油果树(Butyrospermum parkii)种子提取的浅黄色的或乳白色天然油脂。在一些实例中,牛油果脂是可商购的。在一些实例中,牛油果脂可以由HallStar公司以商品名Shea Butter–Ultra Refined提供。
PEG-50牛油果脂是牛油果脂的水溶性衍生物。在一些实例中,PEG-50牛油果脂是从Vantage Specialty Ingredients以商品名SB-50商购的。在一些方面,PEG-50牛油果脂能够有助于皮肤调理、软化和润肤。在一些方面,PEG-50牛油果脂有助于增加发泡。在一些方面,不需要加热就可以将PEG-50牛油果脂添加至组合物;因此其可以通过冷工艺添加至组合物。
水合硅石可以有不同的形状和大小,并且可以包括球形颗粒。这些颗粒的一个商业来源是Evonik公司(德国)以商品名SIPERNATTM 2200。在一些方面,水合硅石是去角质剂。
该成分的组合可以用于不同产品以处理各种皮肤状态。以非限制性实例的方式:霜可以对干燥皮肤提供迅速缓解和/或舒缓,吸收迅速,在应用至皮肤后没有残留,光滑、滋润、水合、软化和/或改善皮肤和/或毛发外观和/或状态;清洗剂可以有助于清洁皮肤和/或毛发的过剩的油、皮脂和/或颗粒,使皮肤和/或毛发光滑,和/或使皮肤和/或毛发去角质。
B.成分的量
预期本发明所述组合物可以包含任意量的本说明书所讨论成分。该组合物还可包含在本说明书全文中所描述的附加成分(例如颜料或附加化妆品或药物成分)的任意数量组合。在该组合物中任意成分的浓度可以改变。例如,在非限制性实施方案中,该组合物在其最终形式中可以包含、主要由以下成分组成或由以下成分组成,例如至少大约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%、0.0550%、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%或其中可得到任何范围的至少一种在本说明书的全文和权利要求所提及的成分。在非限制性方面,该百分比可以按总组合物的重量或体积进行计算。本领域普通技术人员会理解,给定组合物的浓度可以根据成分的增加、替换和/或减少而改变。
C.载剂
本发明的组合物可以包含或被并入所有类型的载剂和载体中。载剂或载体可以是药学上或皮肤病学上可接受的载剂或载体。载剂或载体的非限制性实例包括水、甘油、醇、油、含有机硅的化合物、有机硅化合物和蜡。变体和其它合适的载剂对于熟练技术人员是明显的,并且适用于本发明。在某些方面,化合物、成分和试剂的浓度和组合可以以使得组合是化学相容的并且不形成终产品沉淀的复合物的方式进行挑选。
D.结构
可以将本发明的组合物构造或配制为各种不同形式。非限制性实例包括乳液(例如,油包水、水包油包水、水包油、水包有机硅、有机硅包水、油包水包油、有机硅包水包油型乳剂)、霜、露、溶液(水溶液和水乙醇溶液两者)、无水基质(例如口红和粉末)、凝胶、面膜、撕除式面膜和软膏。变体和其它结构对于本领域技术人员是明显的并且适用于本发明。
E.附加成分
除了本发明所公开成分的组合之外,组合物还可以包含附加成分,例如化妆品成分和药物有效成分。这些附加成分的非限制性实例在以下分段中进行描述。
1.化妆品成分
CTFA国际化妆品成分词典和手册(2004和2008)描述了可以在本发明环境下使用的各种非限制性化妆品成分。这些成分种类的实例包括:香味剂(人造的和天然的;例如葡萄糖酸、苯氧乙醇和三乙醇胺)、染料和着色成分(例如蓝色1号、蓝色1号色淀、红色40号、二氧化钛、D&C蓝色4号、D&C绿色5号、D&C橙色4号、D&C红色17号、D&C红色33号、D&C紫色2号、D&C黄色10号和D&C黄色11号)、调味剂/芳香剂(例如甜叶(Stevia rebaudiana)提取物和薄荷醇)、吸附剂、润滑剂、溶剂、滋润剂(包括例如润肤剂、滋润剂、成膜剂、闭塞剂和影响皮肤天然滋润机制的试剂)、防水剂、紫外吸收剂(物理和化学吸收剂,例如对氨基苯甲酸(“PABA”)和相应的PABA衍生物、二氧化钛、氧化锌等)、精油、维生素(例如A、B、C、D、E和K)、微量金属(例如锌、钙和硒)、抗刺激物(例如类固醇和非甾体抗炎药)、植物提取物(例如芦荟(Aloevera)、柑橘、黄瓜提取物、银杏(Ginkgo biloba)、人参和迷迭香)、抗菌剂、抗氧化剂(例如BHT和生育酚)、螯合剂(例如EDTA二钠和EDTA四钠)、防腐剂(例如对羟基苯甲酸甲酯和对羟基苯甲酸丙酯)、pH调节剂(例如氢氧化钠和柠檬酸)、吸收剂(例如辛基琥珀酸铝淀粉、高岭土、玉米淀粉、燕麦淀粉、环糊精、滑石和沸石)、皮肤漂白和光亮剂(例如氢醌和烟酰胺乳酸盐)、滋润剂(例如山梨醇、脲、甲基葡糖醇聚醚-20、异构寡糖和甘露醇)、去角质剂、防水剂(例如羟基硬脂酸镁/铝)、皮肤调节剂(例如芦荟提取物、尿囊素、没药醇、神经酰胺、聚二甲基硅氧烷、透明质酸、生物糖胶-1、乙基己基甘油、戊二醇、氢化聚癸烯、辛基十二醇油酸酯和甘草酸二钾)。这些成分中一部分的非限制性实例在以下分段中提供。
a.紫外吸收剂和/或紫外反射剂
可以与本发明的组合物组合使用的紫外吸收剂和/或紫外反射剂包括化学和物理防晒物质。可以使用的化学防晒物质的非限制性实例包括对氨基苯甲酸(PABA)、PABA酯(PABA甘油酯、戊基二甲基PABA酯和辛基二甲基PABA酯)、PABA丁酯、PABA乙酯、乙基二羟基丙基PABA酯、二苯甲酮(氧苯酮、磺异苯酮、二苯甲酮和二苯甲酮-1到二苯甲酮-12)、肉桂酸酯(甲氧基肉桂酸辛酯、对甲氧基肉桂酸异戊酯、辛基甲氧基肉桂酸酯、西诺沙酯、二异丙基肉桂酸甲酯、DEA甲氧基肉桂酸酯、二异丙基肉桂酸乙酯、甘油辛酸酯二甲氧基肉桂酸酯和甲氧基肉桂酸乙酯)、肉桂酸酯、水杨酸酯(均甲基水杨酸酯、水杨酸苄酯、乙二醇水杨酸酯、异丙基苄醇水杨酸酯等)、邻氨基苯甲酸盐/酯、尿刊酸乙酯、原膜散酯、水杨酸辛酯、二苯甲酰基甲烷衍生物(例如阿伏苯宗)、奥克立林、辛基三嗪酮、棓酰棓酸三油酸酯、氨基苯甲酸甘油酯、指甲花醌和二羟丙酮、乙基己基三嗪酮、二辛基丁酰胺基三嗪酮、苯亚甲基丙二酸聚硅氧烷、对苯二亚甲基二莰酮磺酸、苯基二苯并咪唑四磺酸酯二钠、二乙氨基羟基苯甲酰基苯甲酸己酯、双二乙氨基羟基苯甲酰基苯甲酸酯、双苯并恶唑基苯基乙基己基亚氨基三嗪、甲酚曲唑三硅氧烷、亚甲基双苯并***基四甲基丁基苯酚、双乙基己基氧苯酚甲氧苯基三嗪、4-甲基苯亚甲基莰酮、和4-甲氧基肉桂酸异戊酯。物理防晒物质的非限制性实例包括高岭土、滑石、凡士林和金属氧化物(例如二氧化钛和氧化锌)。
b.滋润剂
可以与本发明的组合物一起使用的滋润剂的非限制性实例包括氨基酸、硫酸软骨素、双甘油、赤藓糖醇、果糖、葡萄糖、甘油、甘油聚合物、乙二醇、1,2,6-己三醇、蜂蜜、透明质酸、氢化蜂蜜、氢化淀粉水解物、肌醇、乳糖醇、麦芽糖醇、麦芽糖、甘露醇、天然滋润因子、PEG-15丁二醇、聚甘油山梨醇、吡咯烷酮羧酸盐、PCA钾、丙二醇、异构寡糖、葡萄糖醛酸钠、PCA钠、山梨醇、蔗糖、海藻糖、脲和木糖醇。
其它实例包括乙酰化羊毛脂、乙酰化羊毛脂醇、丙氨酸、藻类提取物、翠叶芦荟(Aloe barbadensis)、翠叶芦荟提取物、翠叶芦荟凝胶、药蜀葵(Althea officinalis)提取物、杏仁油、精氨酸、精氨酸天冬氨酸酯、山金车(Arnica montana)提取物、天冬氨酸、鳄梨(Persea gratissima)油、屏障鞘脂、丁醇、蜂蜡、山萮醇、β-谷甾醇、桦木(Betula alba)树皮提取物、紫草(Borago officinalis)提取物、假叶树(Ruscus aculeatus)提取物、丁二醇、金盏花(Calendula officinalis)提取物、金盏花油、小烛树(Euphorbia cerifera)蜡、菜籽油、辛酸/癸酸甘油三酯、豆蔻(Elettaria cardamomum)油、巴西棕榈(Coperniciaerifera)蜡、胡萝卜(Daucus carota sativa)油、蓖麻(Ricinus communis)油、神经酰胺、地蜡、鲸蜡硬脂醇聚醚-5、鲸蜡硬脂醇聚醚-12、鲸蜡硬脂醇聚醚-20、鲸蜡硬脂醇辛酸酯、鲸蜡醇聚醚-20、鲸蜡醇聚醚-24、鲸蜡醇乙酸酯、鲸蜡醇辛酸酯、鲸蜡醇棕榈酸酯、洋甘菊(Anthemis nobilis)油、胆固醇、胆固醇酯、胆甾醇羟基硬脂酸酯、柠檬酸、鼠尾草(Salviasclarea)油、可可(Theobroma cacao)脂、可可辛酸酯/癸酸酯、椰子(Cocos nucifera)油、胶原蛋白、胶原蛋白氨基酸、玉米(Zea mays)油、脂肪酸、癸基油酸酯、二甲基硅氧烷共聚醇、聚二甲基硅氧烷醇、己二酸二辛酯、琥珀酸二辛酯、二聚季戊四醇六辛酸酯/六癸酸酯、DNA、赤藓糖醇、乙氧基乙二醇、亚油酸乙酯、桉树(Eucalyptus globulus)油、月见草(Oenothera biennis)油、脂肪酸、天竺葵(Geranium maculatum)油、葡萄糖胺、葡萄糖谷氨酸酯、谷氨酸、甘油聚醚-26、甘油、丙三醇、二硬脂酸甘油酯、羟基硬脂酸甘油酯、月桂酸甘油酯、亚油酸甘油酯、豆蔻酸甘油酯、油酸甘油酯、硬脂酸甘油酯、硬脂酸甘油酯SE、甘氨酸、乙二醇硬酯酸酯、乙二醇硬酯酸酯SE、葡糖氨基葡聚糖、葡萄(Vitis vinifera)籽油、榛子(Corylus americana)坚果油、己二醇、透明质酸、红花(Carthamus tinctorius)油、氢化蓖麻油、氢化可可甘油酯、氢化椰子油、氢化羊毛脂、氢化卵磷脂、氢化棕榈油甘油酯、氢化棕榈仁油、氢化大豆油、氢化牛脂甘油酯、氢化植物油、水解胶原蛋白、水解弹性蛋白、水解葡糖氨基葡聚糖、水解角蛋白、水解大豆蛋白、羟化羊毛脂、羟基脯氨酸、硬脂酸异鲸蜡醇酯、异鲸蜡醇硬脂酰基硬脂酸酯、油酸异癸酯、异硬脂酸异丙酯、羊毛脂酸异丙酯、肉豆蔻酸异丙酯、棕榈酸异丙酯、硬脂酸异丙酯、异硬脂酰胺DEA、异硬脂酸、异硬脂醇乳酸酯、异硬脂醇新戊酸酯、茉莉(Jasminum officinale)油、霍霍巴(Buxus chinensis)油、海藻、石栗(Aleurites moluccana)坚果油、乳酰胺MEA、羊毛脂醇聚醚-16、羊毛脂醇聚醚-10乙酸酯、羊毛脂、羊毛脂酸、羊毛脂醇、羊毛脂油、羊毛脂蜡、薰衣草(Lavandula angustifolia)油、卵磷脂、柠檬(Citrus medica limonum)油、亚麻油酸、亚麻酸、澳洲坚果(Macadamiaternifolia)油、麦芽糖醇、母菊(Chamomilla recutita)油、甲基葡糖倍半硬脂酸酯、甲基硅烷醇PCA、矿物油、貂油、被孢霉油、肉豆蔻醇乳酸酯、肉豆蔻醇肉豆蔻酸酯、肉豆蔻醇丙酸酯、新戊二醇二辛酸酯/二癸酸酯、辛基月桂醇、辛基月桂醇肉豆蔻酸酯、辛基月桂醇硬脂酰基硬脂酸酯、羟基硬脂酸辛酯、棕榈酸辛酯、水杨酸辛酯、硬脂酸辛酯、油酸、橄榄(Oleaeuropaea)油、橙(Citrus aurantium dulcis)油、棕榈(Elaeis guineensis)油、棕榈酸、泛硫乙胺、泛醇、泛醇基***、石蜡、PCA、桃仁油、花生(Arachis hypogaea)油、PEG-8C12-18酯、PEG-15椰油烷基胺、PEG-150二硬脂酸酯、PEG-60甘油异硬脂酸酯、PEG-5甘油硬脂酸酯、PEG-30甘油硬脂酸酯、PEG-7氢化蓖麻油、PEG-40氢化蓖麻油、PEG-60氢化蓖麻油、PEG-20甲基葡糖倍半硬脂酸酯、PEG40失水山梨醇全油酸酯、PEG-5大豆甾醇、PEG-10大豆甾醇、PEG-2硬脂酸酯、PEG-8硬脂酸酯、PEG-20硬脂酸酯、PEG-32硬脂酸酯、PEG-40硬脂酸酯、PEG-50硬脂酸酯、PEG-100硬脂酸酯、PEG-150硬脂酸酯、十五酸内酯、薄荷(Mentha piperita)油、凡士林、磷脂、浮游生物提取物、多氨基糖缩合物、聚二异硬脂酸甘油酯-3、聚季铵盐-24、聚山梨醇酯20、聚山梨醇酯40、聚山梨醇酯60、聚山梨醇酯80、聚山梨醇酯85、肉豆蔻酸钾、棕榈酸钾、丙二醇、丙二醇二辛酸酯/二癸酸酯、丙二醇二辛酸酯、丙二醇二壬酸酯、丙二醇月桂酸酯、丙二醇硬脂酸酯、丙二醇硬脂酸酯SE、PVP、吡哆醇二棕榈酸酯、视黄醇、视黄醇棕榈酸酯、米(Oryza sativa)糠油、RNA、迷迭香(Rosmarinus officinalis)油、玫瑰油、红花(Carthamus tinctorius)油、鼠尾草(Salvia officinalis)油、檀香(Santalum album)油、丝氨酸、血清蛋白、芝麻(Sesamum indicum)油、牛油果(Butyrospermum)脂、蚕丝粉、软骨素硫酸钠、透明质酸钠、乳酸钠、棕榈酸钠、PCA钠、聚谷氨酸钠、可溶胶原蛋白、失水山梨醇月桂酸酯、失水山梨醇油酸酯、失水山梨醇棕榈酸酯、失水山梨醇倍半油酸酯、失水山梨醇硬脂酸酯、山梨醇、大豆(Glycine soja)油、鞘脂、角鲨烷、角鲨烯、硬脂酰胺MEA-硬脂酸酯、硬脂酸、硬脂氧基聚二甲基硅氧烷、硬脂氧基三甲基硅烷、硬脂醇、硬脂醇甘草亭酸酯、硬脂醇庚酸酯、硬脂醇硬脂酸酯、葵花(Helianthus annuus)籽油、甜杏仁(Prunus amygdalusdulcis)油、合成蜂蜡、生育酚、乙酸生育酚酯、生育酚亚油酸酯、三山嵛精、十三烷醇新戊酸酯、十三烷醇硬脂酸酯、三乙醇胺、三硬脂酸精、脲、植物油、水、蜡、小麦(Triticumvulgare)胚芽油和依兰(Cananga odorata)油。
c.抗氧化剂
可以与本发明的组合物一起使用的抗氧化剂的非限制性实例包括乙酰半胱氨酸、抗坏血酸多肽、抗坏血酸二棕榈酸酯、抗坏血酸甲基硅烷醇果胶酸酯、抗坏血酸棕榈酸酯、抗坏血酸硬脂酸酯、BHA、BHT、叔丁基氢醌、半胱氨酸、半胱氨酸HCI、二戊基氢醌、二叔丁基氢醌、二鲸蜡醇硫代二丙酸酯、二油基生育酚甲基硅烷醇、抗坏血酸硫酸酯二钠、二硬脂醇硫代二丙酸酯、双十三烷醇硫代二丙酸酯、没食子酸月桂酯、异抗坏血酸、抗坏血酸酯、阿魏酸乙酯、阿魏酸、没食子酸酯、氢醌、巯基乙酸异辛酯、曲酸、抗坏血酸镁、抗坏血酸磷酸酯镁、甲基硅烷醇抗坏血酸酯、天然植物抗氧化剂例如绿茶或葡萄籽提取物、去甲二氢愈创木酸、没食子酸辛酯、苯巯基乙酸、磷酸抗坏血酸酯生育酚酯钾、亚硫酸钾、没食子酸丙酯、醌、迷迭香酸、抗坏血酸钠、亚硫酸氢钠、异抗坏血酸钠、偏亚硫酸氢钠、亚硫酸钠、超氧化物歧化酶、巯基乙酸钠、山梨醇缩糠醛、硫二甘醇、亚硫基二乙酰胺、硫二乙酸、巯基乙酸、硫代乳酸、硫代水杨酸、生育酚聚氧醚-5、生育酚聚醚-10、生育酚聚醚-12、生育酚聚醚-18、生育酚聚醚-50、生育酚、托可索伦、乙酸生育酚酯、生育酚亚油酸酯、生育酚烟酸酯、生育酚琥珀酸酯和三(壬基酚)亚磷酸酯。
d.结构化剂
在其它非限制性方面,本发明的组合物可以包含结构化剂。在某些方面,结构化剂帮助给组合物提供流变学特征以有助于组合物的稳定性。在其它方面,结构化剂还可以起乳化剂或表面活性剂的作用。结构化剂的非限制性实例包括硬脂酸、棕榈酸、硬脂醇、鲸蜡醇、山嵛醇、硬脂酸、棕榈酸、具有平均约1到约21个环氧乙烷单元的硬脂醇的聚乙二醇醚、具有平均约1到约5个环氧乙烷单元的鲸蜡醇的聚乙二醇醚、及其混合物。
e.乳化剂
在本发明的某些方面,组合物不包含乳化剂。然而,在其它方面,组合物可以包含一种或更多种乳化剂。乳化剂可以降低相间表面张力并改善乳液的剂型和稳定性。乳化剂可以是非离子乳化剂、阳离子乳化剂、阴离子乳化剂和两性离子乳化剂(参见McCutcheon(1986);美国专利5011681号;4421769号;3755560号)。非限制性实例包括甘油酯、丙二醇酯、聚乙二醇的脂肪酸酯、聚丙二醇的脂肪酸酯、山梨醇的酯、失水山梨醇酐的酯、羧酸共聚物、葡萄糖的酯和醚、乙氧基化酯、乙氧基化醇、磷酸烷基酯、聚氧乙烯脂肪醚磷酸酯、脂肪酸酰胺、酰基乳酸酯、脂肪酸盐、TEA硬脂酸酯、油醇聚醚-3磷酸酯DEA盐、聚乙二醇20失水山梨醇单月桂酸酯(聚山梨醇酯20)、聚乙二醇5大豆甾醇、硬脂醇聚醚-2、硬脂醇聚醚-20、硬脂醇聚醚-21、鲸蜡硬脂醇聚醚-20、鲸蜡硬脂醇基葡萄糖苷、鲸蜡硬脂醇、C12-13链烷醇聚醚-3、PPG-2甲基葡萄糖醚二硬脂酸酯、PPG-5-鲸蜡醇聚醚-20、双-PEG/PPG-20/20聚二甲基硅氧烷、鲸蜡醇聚醚-10、聚山梨醇酯80、鲸蜡醇磷酸酯、鲸蜡醇磷酸酯钾、二乙醇胺鲸蜡醇磷酸酯、聚山梨醇酯60、甘油硬脂酸酯、PEG-100硬脂酸酯、花生醇、花生醇葡糖苷、及其混合物。
f.含有机硅的化合物
在非限制性方面,含有机硅的化合物包括分子主链由交替的硅和氧原子与连接在硅原子上的侧基组成的聚合产物家族中的任何成员。通过改变-Si-O-链的长度、侧基和交联,有机硅可以合成为各种材料。其稠度可以从液体到凝胶到固体改变。
可以在本发明的环境下使用的含有机硅的化合物包括在本说明书中所描述的或本领域普通技术人员已知的那些。非限制性实例包括硅油(例如挥发性和非挥发性油)、凝胶和固体。在某些方面,含有机硅的化合物包括硅油,例如聚有机硅氧烷。聚有机硅氧烷的非限制性实例包括聚二甲基硅氧烷、环聚二甲基硅氧烷、聚硅氧烷-11、苯基聚三甲基硅氧烷、聚三甲基硅氨基二甲基硅氧烷、硬脂氧基三甲基硅烷、或这些的混合物和其它以任何给定比例的有机硅氧烷材料以根据预期的应用(例如,对特定区域例如皮肤、毛发或眼睛)达到所期望稠度和应用特征。“挥发性硅油”包括具有低蒸发热的硅油,即通常低于约50卡每克硅油。挥发性硅油的非限制性实例包括环聚二甲基硅氧烷,例如道康宁344流体、道康宁345流体、道康宁244流体和道康宁245流体、挥发硅7207(康涅狄格州,丹伯里,联合碳化物公司);低粘度聚二甲基硅氧烷,即具有约50cst或更低黏度的聚二甲基硅氧烷(例如,如道康宁200至0.5cst流体的聚二甲基硅氧烷)。道康宁流体可以从密歇根州米德兰的DowCorning Corporation购得。在CTFA化妆品成分词典第三版中(通过引用并入),将环聚二甲基硅氧烷和聚二甲基硅氧烷分别描述为环状二甲基聚硅氧烷化合物和用三甲基硅氧基单元封端的完全甲基化线性硅氧烷混合物。可以在本发明的环境下使用的其它非限制性挥发性硅油包括从纽约州沃特福德的General Electric Co.的有机硅产品部门和密歇根州艾德里安Stauffer Chemical Co.的SWS有机硅部门购得的那些。
g.去角质剂
去角质剂包括去除皮肤外表面死皮细胞的成分。这些试剂可以通过机械的、化学的和/或其他手段发挥作用。机械去角质剂的非限制性实例包括研磨剂如浮石、硅石、织物、纸、贝壳、玻璃粉、固态晶体、固态聚合物等。化学去角质剂的非限制性实例包括酸和酶去角质剂。可以用作去角质剂的酸包括但不限于,乙醇酸、乳酸、柠檬酸、α羟基酸、β羟基酸等。可以预期本领域技术人员已知的其他去角质剂在本发明背景内也是有用的。
h.精油
精油包括来自草本植物、花朵、树木和其它植物的油。这类油一般以植物细胞间微小液滴存在,并可以用本领域技术人员已知的若干方法进行提取(例如,蒸气蒸馏、脂吸法(即使用脂肪提取)、浸渍、溶剂提取或机械压榨)。当这些类型的油暴露于空气时,其趋于挥发(即挥发性油)。因此,虽然许多精油是无色的,但是随着时间可以使其氧化并且颜色变得更深。精油不溶于水,但溶于醇、醚、固定油(植物油)和其它有机溶剂。精油中发现的一般物理特征包括从约160℃到240℃变化的沸点和从约0.759到约1.096的密度。
一般用发现油的植物命名精油。例如,玫瑰油或薄荷油分别来自玫瑰或薄荷植物。可以在本发明的环境下使用的精油的非限制性实例包括芝麻油、澳洲坚果油、茶树油、月见草油、西班牙鼠尾草油、西班牙迷迭香油、芫荽油、百里香油、众香果油、玫瑰油、大茴香油、凤仙花油、佛手柑油、玫瑰木油、香柏油、甘菊油、鼠尾草油、香紫苏油、丁香油、柏木油、桉树油、茴香油、海茴香油、乳香油、天竺葵油、姜油、葡萄柚油、茉莉油、杜松子油、薰衣草油、柠檬油、柠檬草油、青柠油、柑橘油、马郁兰油、没药油、橙花油、橙油、广霍油、胡椒油、黑胡椒油、苦橙叶油、松树油、奥图玫瑰油、迷迭香油、檀香油、绿薄荷油、甘松油、香根草油、冬青油、依兰油。可以预期本领域技术人员已知的其它精油在本发明的环境下也是有用的。
i.增稠剂
包括增稠剂或凝胶剂在内的增稠剂,包括可以增加组合物黏度的物质。增稠剂包括可以增加组合物黏度而基本上不改变组合物内活性成分功效的那些。增稠剂还可以增加本发明组合物的稳定性。在本发明的某些方面,增稠剂包括氢化聚异丁烯、三羟基硬脂酸甘油酯、丙烯酰二甲基牛磺酸铵/vp共聚物、或其混合物。
可以在本发明的环境下使用的附加增稠剂的非限制性实例包括羧酸聚合物、交联的聚丙烯酸酯聚合物、聚丙烯酰胺聚合物、多糖和胶。羧酸聚合物的实例包括含有衍生自丙烯酸的一种或更多种单体的交联化合物、取代的丙烯酸及这些丙烯酸和取代的丙烯酸的盐和酯,其中交联剂含有两个或更多个碳-碳双键,并衍生自多元醇(参见美国专利5087445号;4509949号;2798053号;CTFA国际化妆品成分词典,第四版,1991,第12和80页)。市售羧酸聚合物的实例包括卡波姆,其为丙烯酸与蔗糖或季戊四醇的烯丙基醚交联的均聚物(例如,购自B.F.Goodrich的CarbopolTM 900系列)。
交联的聚丙烯酸酯聚合物的非限制性实例包括阳离子型和非离子型聚合物。在美国专利5100660号;4849484号;4835206号;4628078号;4599379号中描述了实例。
聚丙烯酰胺聚合物(包括非离子型聚丙烯酰胺聚合物,其包括经取代的支化或非支化聚合物)的非限制性实例包括聚丙烯酰胺、异构烷烃和月桂醇聚醚-7、丙烯酰胺与用丙烯酸取代的丙烯酸和经取代的丙烯酰胺的多嵌段共聚物。
多糖的非限制性实例包括纤维素、羧甲基羟乙基纤维素、乙酸丙酸羧酸纤维素、羟乙基纤维素、羟乙基乙基纤维素、羟丙基纤维素、羟丙基甲基纤维素、甲基羟乙基纤维素、微晶纤维素、纤维素硫酸钠、及其混合物。其他实例为烷基取代的纤维素,其中纤维素聚合物的羟基被羟烷基化(优选地羟乙基化或羟丙基化)以形成羟烷基化的纤维素,其然后用C10至C30直链或支链烷基基团通过醚键进一步改性。一般这些聚合物为C10至C30直链或支链醇与羟烷基纤维素的醚。其它有用的多糖包括硬葡聚糖类,其每3个单元包含具有(1-6)连接的葡萄糖的(1-3)连接的葡萄糖单元的直链。
本发明可以使用的胶的非限制性实例包括***胶、琼脂、藻胶、藻酸、藻酸铵、支链淀粉、藻酸钙、角叉菜胶钙、肉毒碱、角叉菜胶、糊精、明胶、结冷胶、瓜尔豆胶、瓜尔胶羟丙基三甲基氯化铵、锂蒙脱石、透明质酸、水合二氧化硅、羟丙基壳聚糖、羟丙基瓜尔胶、卡拉亚胶、巨藻、角豆胶、纳豆胶、藻酸钾、角叉菜胶钾、藻酸丙二醇酯、菌核胶、羧甲基葡聚糖钠、角叉菜胶钠、黄蓍胶、黄原胶、及其混合物。
j.防腐剂
在本发明的环境下可以使用的防腐剂的非限制性实例包括季铵盐防腐剂(例如聚季铵盐-1和苄烷铵卤化物(例如苯扎氯铵(“BAC”)和苯扎溴铵)、对羟基苯甲酸酯(例如对羟基苯甲酸甲酯和对羟基苯甲酸丙酯)、苯氧基乙醇、苄醇、氯丁醇、苯酚、山梨酸、硫汞撒、或其组合。
2.药物成分
可以预期的是药物活性成分对本发明的组合物也是有用的。药物活性成分的非限制性实例包括抗粉刺剂、用于处理酒渣鼻的试剂、止痛剂、麻醉剂、肛肠剂、抗组胺药、包括非甾族消炎药在内的消炎剂、抗生素、抗真菌剂、抗病毒素、抗微生物剂、抗癌活性物、抗疥螨剂、灭虱剂、抗肿瘤药、防汗药、止痒剂、抗牛皮癣药、抗脂溢剂、生物活性蛋白质和多肽、烧伤治疗剂、烧灼剂、脱色剂、脱毛剂、尿布疹治疗剂、酶、毛发生长刺激剂、包括DFMO及其盐和类似物的毛发生长抑制剂、止血剂、角质分离剂、口疮处理剂、唇疱疹处理剂、牙齿和牙周治疗剂、光敏感活性物、皮肤保护剂/屏障剂、包括激素和皮质激素的类固醇、晒伤治疗剂、遮光剂、经皮活性物、鼻活性物、***活性物、疣处理剂、创伤处理剂、创伤愈合剂等。
F.试剂盒
可以预期的是试剂盒也用于本发明的某些方面。例如,本发明的组合物可以包括在试剂盒内。试剂盒可以包括容器。容器可以包括瓶子、金属管、层压管、塑料管、分配器、增压容器、屏障容器、包装、分室、口红容器、压缩容器、能够保存化妆品组合物的化妆品盘、或其它类型的容器例如注射或吹塑成型的塑料容器,其保存分散体或组合物或所期望瓶子、分配器或包装。试剂盒和/或容器在其表面可包含标记。例如,标记可以是单词、短语、缩写、图片或符号。
容器可以分配预定量的组合物。在其他实施方案中,可以挤压容器(例如金属、层压或塑料管)以分配组合物的所期望量。组合物可以分配为喷雾、气雾剂、液体、流体或半固体。容器可以具有喷雾、泵或挤压机构。试剂盒还可以包含使用试剂盒成分以及使用任何包含于容器内的组合物的说明书。说明书可以包含如何施用、使用和保存组合物的说明。
实施例
包括以下实施例以说明本发明的优选实施方案。本领域技术人员应理解以下实施例中所公开的技术能代表本发明人发现的在本发明实践中发挥良好作用的技术,因此能够认为构成用于其实践的优选实施方案。然而,根据本公开,本领域技术人员应理解,在不脱离本发明的精神和范围的情况下,在所公开的具体实施方案中可以做许多改变并仍获得相同或相似的结果。
实施例1
将含有实施例1的成分的制剂制备为局部用皮肤或毛发组合物。将表1和2中的制剂制备为洗面奶。将表3中的制剂制备为霜。
本文所公开和要求保护的所有组合物和/或方法可以根据本公开无需过度实验即可以进行和实现。尽管本发明的组合物和方法已经按照优选实施方案进行了描述,但是对于本领域技术人员明显的是,可以对本文所描述方法的组合物和/或方法以及步骤或步骤顺序进行变化,而不脱离本发明的概念、精神和范围。更具体地,明显的是化学和生理两方面都相关的某些试剂可以替代本文所描述的试剂,然而会实现相同或相似的结果。对本领域技术人员明显的所有这类相似替代和改变都视为在如由所附权利要求限定的本发明的精神、范围和概念内。
表1*
成分 | %浓度(以重量计) |
水 | 75 |
月桂醇硫酸酯TEA盐 | 10 |
水合硅石 | 5 |
丙烯酸酯共聚物 | 2 |
椰油酰胺丙基甜菜碱 | 2 |
氯化钠 | 1 |
三乙醇胺 | 1 |
丙二醇 | 1 |
氢化霍霍巴油 | 1 |
羟乙基纤维素 | 0.6 |
对羟基苯甲酸甲酯 | 0.2 |
EDTA二钠 | 0.1 |
柠檬酸(任选的) | 0.3 |
杏籽粉(任选的) | 0.2 |
桃籽粉(任选的) | 0.1 |
赋形剂** | 适量 |
*可以通过在70℃至75℃加热下在烧杯中混合成分直到均匀而制备制剂。然后,可以将制剂冷却到标准室温(20℃至25℃)。另外,如果需要,例如可以添加附加成分以改变组合物的流变特性。
**例如可以添加赋形剂以改变组合物的流变特性。或者,可以改变水的量,只要组合物中水的量为至少60重量%,优选60重量%至85重量%。
表2*
成分 | %浓度(以重量计) |
水 | 81 |
月桂醇硫酸酯TEA盐 | 8 |
水合硅石 | 3.5 |
椰油酰胺丙基甜菜碱 | 2 |
三乙醇胺 | 1 |
丙烯酸酯/C10-30烷基丙烯酸酯交联聚合物 | 1 |
PEG-50牛油果脂 | 0.8 |
苯氧乙醇 | 0.5 |
辛甘醇 | 0.3 |
氯化钠 | 0.3 |
EDTA二钠 | 0.1 |
乙基己基甘油 | 0.1 |
己二醇 | 0.1 |
聚山梨醇酯20(任选的) | 0.8 |
氢化霍霍巴油(任选的) | 0.3 |
硬脂醇硬脂酸酯(任选的) | 0.2 |
刺梨提取物(任选的) | 0.05 |
赋形剂** | 适量 |
*可以通过在70℃至75℃加热下在烧杯中混合成分直到均匀来制备制剂。然后,可以将制剂冷却到标准室温(20℃至25℃)。另外,如果需要,例如可以添加附加成分以改变组合物的流变特性。
**例如可以添加赋形剂以改变组合物的流变特性。或者,可以改变水的量,只要组合物中水的量为至少60重量%,优选65重量%至90重量%。
表3*
成分 | %浓度(以重量计) |
水 | 72 |
牛油果脂 | 5 |
甘油 | 5 |
鲸蜡硬脂醇 | 4 |
硬脂酸甘油酯 | 3 |
丙二醇 | 3 |
葵花籽油 | 2 |
红花籽油 | 1 |
PEG-100硬脂酸酯 | 0.8 |
苯氧乙醇 | 0.8 |
丙二醇 | 0.6 |
杏仁油 | 0.5 |
聚二甲基硅氧烷 | 0.4 |
辛甘醇 | 0.3 |
生育酚乙酸酯 | 0.3 |
黄原胶 | 0.2 |
聚丙烯酸酯-13 | 0.2 |
EDTA二钠 | 0.1 |
乙基己基甘油 | 0.1 |
赋形剂** | 适量 |
*可以通过在70℃至75℃加热下在烧杯中混合成分直到均匀而制备制剂。然后,可以将制剂冷却到标准室温(20℃至25℃)。另外,如果需要,例如可以添加附加成分以改变组合物的流变特性。
**例如可以添加赋形剂以改变组合物的流变特性。或者,可以改变水的量,只要组合物中水的量为至少60重量%,优选60重量%至85重量%。
实施例2
(分析)
可以用于确定本说明书全文和权利要求书所公开的成分或该成分的任意组合或具有所述成分组合的组合物中的任一种的功效的分析可以通过本领域技术人员已知的方法进行确定。以下是可以在本发明的环境中使用的非限制性分析。应认识到,可以使用其它测试过程,包括例如客观过程和主观过程。
B16色素沉着分析:黑色素生成是黑色素细胞产生黑色素的过程,黑色素是给予皮肤、毛发和眼睛颜色的天然产生的色素。抑制黑素生成有益于预防皮肤变黑和减轻与老化有关的黑斑。该生物分析采用B16-F1黑色素细胞(ATCC)以分析化合物对黑色素生成的效果,该黑色素细胞是永生化小鼠黑色素瘤细胞系。该分析的终点是黑色素生成和细胞活性的分光光度测量。可以在37℃下10%的CO2中用10%的胎牛血清(Mediatech)在标准DMEM生长培养基中培养B16-F1黑素细胞,然后用本说明书所公开的活性成分、该成分的组合或具有该组合的组合物中的任一种处理6天。在培养之后,通过405nm的吸光度测量黑色素分泌,定量细胞活性。
胶原蛋白刺激分析:胶原蛋白是对皮肤结构关键的细胞外基质蛋白。胶原蛋白合成增加有助于改善皮肤紧实度和弹性。该生物分析可以用来检测本说明书所公开的活性成分、该成分的组合或具有所述组合的组合物中的任一个对人表皮纤维母细胞生成前胶原肽(胶原蛋白前体)的影响。该分析的终点是反映前胶原肽存在和细胞活性的分光光度测量。该分析采用定量夹心酶免疫分析技术,通过将原胶原肽特异性单克隆抗体预先涂覆在微孔板上。可以将标准品和样品移液到孔中,存在的任何原胶原肽与固定化抗体结合。在洗去所有未结合物质后,将原胶原肽特异性酶联多克隆抗体添加到孔。在冲洗以去除所有未结合抗体-酶反应物之后,可以将底物溶液添加到孔,显色与最初步骤中结合的原胶原肽的量成比例,使用酶标仪在450nm处检测。可以停止显色并可以测量颜色的强度。为了产生样品和对照,可以将在37℃下10%的CO2中利用10%的胎牛血清(Mediatech)在标准DMEM生长培养基中培养的亚融合正常人成熟表皮成纤维母细胞(Cascade Biologics)用本说明书中所公开的成分的组合或具有所述组合的组合物中的每一种处理3天。在培养之后,可以收集细胞培养基,使用Takara夹心酶联免疫吸附分析(ELISA)(#MK101)定量原胶原肽分泌的量。
弹性蛋白刺激分析:弹性蛋白是帮助皮肤在拉伸或压缩后恢复形状的***蛋白。弹性蛋白也是重要的承载蛋白,其用于机械能需要储存之处。通过在赖氨酰氧化酶催化的反应中连接许多可溶性原弹性蛋白分子而形成弹性蛋白。通过使用针对弹性蛋白的免疫荧光抗体染色培养的人成纤维细胞,在培养的人成纤维细胞中可以监测弹性蛋白分泌和弹性蛋白纤维。
层粘连蛋白和纤连蛋白刺激分析:层粘连蛋白和纤连蛋白是真皮-表皮连接(DEJ)(也称为基膜)中的主要蛋白质。DEJ位于真皮和表皮联结之间,形成叫做网脊的指状突出。表皮细胞从真皮血管中接收其养分。网脊增大暴露于这些血管和所需养分的表皮表面积。DEJ提供两种组织室的粘连,控制皮肤完整性。层粘连蛋白和纤连蛋白是位于DEJ中的两种结构糖蛋白。考虑到将细胞保持在一起的胶,真皮成纤维细胞分泌层粘连蛋白和纤连蛋白以帮助促进表皮细胞和DEJ的细胞内和细胞间粘连。通过定量经培养的人成纤维细胞的细胞上清液中的层粘连蛋白和纤连蛋白,所述经培养的人成纤维细胞用含有或不含有1.0%终浓度的测试成分的培养基处理3天,可以监测层粘连蛋白和纤连蛋白分泌。在培养过后,可以在酶联免疫吸附试验(ELISA)中使用针对每种蛋白的荧光免疫抗体测量层粘连蛋白和纤连蛋白含量。将测量值归一化为细胞代谢活性,如通过3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺苯基)-2H-四唑(MTS)生物转化所确定的。
肿瘤坏死因子-α(TNF-α)分析:TNF超家族的原型配体TNF-α是在炎症中起主要作用的多效细胞因子。其表达增加与促炎活性上调有关。该生物分析可以用于分析本说明书所公开的活性成分、该成分的组合或具有所述组合的组合物中的任一种对人表皮角化细胞生成TNF-α的影响。该分析的终点可以是反映TNF-α存在和细胞活性的分光光度测量。该分析采用定量夹心酶免疫分析技术,通过将TNF-α特异性单克隆抗体预先涂覆在微孔板上。可以将标准品和样品移液到孔中,存在的任何TNF-α与固定化抗体结合。在洗去所有未结合物质后,可以将TNF-α特异性酶联多克隆抗体添加到孔。冲洗以去除所有未结合抗体-酶反应物之后,可以将底物溶液添加到孔,显色与最初步骤中结合的TNF-α的量成比例,使用酶标仪在450nm处检测。可以停止显色并测量颜色的强度。可以将在37℃下5%的CO2中在EpiLife标准生长培养基(Cascade Biologics)中培养的亚融合正常人成熟角质细胞(Cascade Biologics)用佛波醇-12-豆蔻酸-13-乙酸酯(PMA,10ng/ml,Sigma Chemical,#P1585-1MG)和本说明书中所公开的活性成分、该成分的组合或具有所述组合的组合物中的每一种处理6小时。PMA已显示导致TNF-α分泌急剧增加,其在处理6小时后达到峰值。在培养之后,可以收集细胞培养基,使用R&D Systems(#DTA00C)的夹心酶联免疫吸附分析(ELISA)定量TNF-α分泌的量。
抗氧化(AO)分析:体外生物分析测量本说明所公开的成分、该成分的组合或具有所述组合的组合物中的任一种的总抗氧化能力。该分析依赖样品中抗氧化剂的能力以抑制(2,2'-联氮-双-[3-乙基苯并噻唑啉磺酸盐])由正铁肌红蛋白氧化为·+。活生物体的抗氧化***包含酶,例如超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶;大分子,例如白蛋白、血浆铜蓝蛋白和铁蛋白;大量小分子,包括抗坏血酸、α-生育酚、β-胡萝卜素、还原型谷胱甘肽、尿酸和胆红素。內源抗氧化剂和食物源性抗氧化剂的总数表示细胞外液的总抗氧化能力。所有不同抗氧化剂的协作提供比单独任何单个化合物更强的对抗反应性氧或氮自由基攻击的保护。因此,总抗氧化能力与测量单独成分获得的抗氧化能力相比可以给出更有意义的生物信息,因为其考虑了血浆和体液中存在的所有抗氧化剂的累积效应。样品中抗氧化剂预防ABTS氧化的能力与Trolox进行比较,Trolox是水溶性生育酚类似物,并以Trolox摩尔当量进行定量。可以使用Cayman Chemical(密歇根州安阿伯,USA)的抗氧化能力试剂盒#709001作为测量本说明中所公开的活性成分、该成分的组合或具有所述组合的组合物中的任一种的总抗氧化能力的体外生物分析。方案可以根据制造商建议进行。
ORAC分析:本说明书所公开的活性成分、该成分的组合或具有所述组合的组合物中的任一种的氧自由基吸收(或吸光度)能力(ORAC)也可以通过测量这些成分或组合物的抗氧化活性进行分析。抗氧活性表明还原经氧化的试剂(抗氧剂)的能力。该分析定量抑制氧化剂活动的程度及所用时间,氧化剂例如已知导致损害细胞(例如皮肤细胞)的氧自由基。本说明书公开的活性成分、该成分的组合或具有该组合的组合物中的任一种的ORAC值可以通过本领域技术人员已知的方法进行确定(参见U.S.公开号2004/0109905和2005/0163880;可商购试剂盒如Zen-Bio ORAC抗氧化分析试剂盒(#AOX-2))。Zen-Bio ORAC抗氧化分析试剂盒测量由于AAPH(2,2'-偶氮二-2-甲基丙基咪二盐酸盐)分解而形成过氧化氢自由基而荧光素荧光随时间的损失。将水溶性维生素E类似物Trolox用作阳性对照,其以剂量依赖的方式抑制荧光素衰减。
蘑菇酪氨酸酶活性分析:在哺乳动物细胞中,酪氨酸酶在来自酪氨酸(和来自多巴色素聚合)的多步生物合成黑色素中催化两个步骤。酪氨酸酶位于黑素色细胞中并产生给予皮肤、毛发和眼睛颜色的黑色素(芳香醌化合物)。可以将经纯化的蘑菇络氨酸酶(Sigma)在存在或不存在本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合与其底物L-Dopa(Fisher)培养。可以在490nm通过比色板读数而评价色素形成。蘑菇络氨酸酶活性的抑制百分比可以通过与未处理的对照相比较来计算,以确定测试成分或其组合抑制纯化酶活性的能力。将试验提取物抑制与曲酸(Sigma)进行比较。
基质金属蛋白酶3和9酶活性(MMP3;MMP9)分析:体外基质金属蛋白酶(MMP)抑制分析。MMP是胞外蛋白酶,凭借其广泛底物特异性在许多正常状态和疾病状态起作用。MMP3底物包括胶原蛋白、纤连蛋白和层粘连蛋白;而MMP9底物包括胶原蛋白VII、纤连蛋白和层粘连蛋白。使用BioMol International的比色药物发现试剂盒用于MMP3(AK-400)和MMP-9(AK-410),该分析设计为测量MMP的蛋白酶活性,使用含硫多肽作为显色底物(Ac-PLG-[2-巯基-4-甲基-戊酰基]-LG-OC2H5)5,6。MMP裂解位点肽键由含硫多肽中的硫酯键替代。该键被MMP水解产生巯基,其与DTNB[5,5'-二硫代双(2-硝基苯甲酸),埃尔曼试剂]反应生成2-硝基-5-硫代苯甲酸,可以通过其在412nm的吸光度进行检测(在pH 6.0和高于7时,ε=13600M-1cm-1)。可以测试本说明书中公开的活性成分、该成分的任一组合或具有所述组合的组合物。
基质金属蛋白酶1酶活性(MMP1)分析:体外基质金属蛋白酶(MMP)抑制分析。MMP是胞外蛋白酶,凭借其广泛的底物特异性在许多正常状态和疾病状态起作用。MMP1底物包括胶原蛋白IV。分子探针Enz/Chek白明胶酶/胶原酶分析试剂盒(#E12055)利用荧光明胶底物检测MMP1蛋白酶活性。在解蛋白裂解后,显示亮绿色荧光,并可以使用荧光酶标仪观测亮绿色荧光以测量酶活性。
将Invitrogen的Enz/Che明胶酶/胶原蛋白酶分析试剂盒(#E12055)设计为测量MMP1酶活性的体外分析。可以测试本说明书所公开的活性成分、该成分的任一组合或具有所述组合的组合物。该分析依赖于经纯化的MMP1酶降解荧光明胶底物的能力。一旦底物被MMP1特异地裂解,则显示亮绿色荧光,并可以使用荧光酶标仪观测亮绿色荧光。在存在或不存经纯化的酶和底物的条件下培养试验材料以确定其蛋白酶抑制能力。
环氧合酶(COX)分析:体外环氧合酶-1和体外环氧合酶-2(COX-1、COX-2)抑制分析。COX是展现环氧合酶和过氧化物酶两者活性的双功能酶。环氧合酶活性将花生四烯酸转化为过氧化氢内过氧化物(***素G2;PGG2),过氧化物酶成分将内过氧化物(***素H2;PGH2)还原为相应的醇,***素、凝血噁烷和环***素的前体。该COX抑制筛选分析测量环氧合酶的过氧化物酶成分。过氧化物酶活性通过监测出现经氧化的N,N,N',N'-四甲基-对苯二胺(TMPD)进行比色分析。该抑制筛选分析包括COX-1和COX-2酶两者,以筛选同工酶特异性抑制剂。可以使用比色COX(绵羊)抑制剂筛选分析(#760111,Cayman Chemical)以分析本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物对经纯化的环氧合酶(COX-1或COX-2)活性的影响。根据制造商的说明书,经纯化的酶、血红素和测试提取物可以在分析缓冲液中混合,并在室温下摇动培养15分钟。在培养之后,可以加入花生四烯酸和比色底物以开始反应。颜色变化可以通过在590nm测定的比色板进行评价。COX-1或COX-2活性抑制百分比可以通过与未处理的对照物比较进行计算以确定测试提取物抑制经纯化酶活性的能力。
脂肪氧合酶(LO)分析:体外脂肪氧合酶抑制分析。LO是非血红素的含铁加双氧酶,其催化分子氧加成到脂肪酸。亚油酸和花生四烯酸是植物和动物中LO的主要底物。然后,可以将花生四烯酸转化为羟基二十三烯(HETE)酸衍生物,其随后转化为白三烯,有效的炎症介质。该分析通过测量利用花生四烯酸培养的脂肪氧合酶(5-LO、12-LO或15-LO)产生的氢过氧化物提供用于筛选脂肪氧合酶抑制剂的精确和方便的方法。可以使用比色LO抑制剂筛选试剂盒(#760700,Cayman Chemical)确定本说明书中所公开的每种活性成分、该成分的任一组合、或具有所述组合的组合物抑制酶活性的能力。可以将经纯化的15-脂肪氧合酶和测试成分在分析缓冲液中混合,并在室温下摇动培养10分钟。在培养之后,可以加入花生四烯酸开始反应,混合物可以在室温下再培养另外10分钟。可以加入比色底物以终止催化,颜色变化可以通过在490nm测定的荧光板进行评价。可以与未处理的对照相比较而计算脂肪氧合酶活性的抑制百分比以确定本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物抑制经纯化酶活性的能力。
弹性蛋白酶分析:可以使用Molecular Probes(俄勒冈州尤金,USA)的弹性蛋白酶分析(试剂盒#E-12056)作为用于测量本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物的弹性蛋白酶活性抑制的体外酶抑制分析。EnzChek试剂盒含有可溶性牛颈韧带弹性蛋白,其可以用染料标记以使共轭荧光能够被淬灭。非荧光底物可以被弹性蛋白酶或其他蛋白酶消化以产生高荧光片段。产生的荧光增强可以用荧光微孔板测定仪进行监测。弹性蛋白底物的酶切产物在约505nm处具有最大吸收,在约515nm处具有最大荧光发射。当使用EnzChek弹性蛋白酶分析试剂盒筛选弹性蛋白酶抑制剂时,可以将肽、N-甲氧基琥珀酰-Ala-Ala-Pro-Val-氯甲基酮用作弹性蛋白的选择性的共同酶抑制剂。
油控制分析:用于测量皮脂腺皮脂分泌减少和/或皮脂腺皮脂产生减少的分析可以通过使用本领域技术人员已知的标准技术进行分析。在一个实例中,可以使用前额。可以将本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物每天1次或2次地施用到前额的一部分一段固定时间(例如1天、2天、3天、4天、5天、6天、7天、8天、9天、10天、11天、12天、13天、14天或更多天),而前额的其他部分不用该组合物处理。在一段固定时间期满后,然后可以通过将细吸油纸施用到经处理的和未经处理的前额皮肤上分析皮脂分泌。这是通过首先用湿布和干布从经处理的和未经处理的区域去除所有皮脂完成的。然后将吸油纸施用到经处理的和未经处理的前额区域,可以围绕前额放置橡皮筋以轻轻将吸油纸压到皮肤上。2小时后,可以移去吸油纸,使其干燥然后进行透照。较深的吸油纸对应于较多的皮脂分泌(或较浅的吸油纸对应于减少的皮脂分泌)。
红斑分析:测量皮肤发红减少的分析可以使用Minolta Chromometer进行评价。皮肤红斑可以通过在受试者前臂施用0.2%的十二烷基硫酸钠溶液引发。该区域用封闭贴片保护24小时。24小时后,除去贴片,可以使用Minolta Chroma Meter的a*值对刺激引发的发红进行评价。a*值测量肤色在红色区域的变化。读数后立即用本说明书所公开的活性成分、该成分的任一组合或具有所述组合的组合物处理该区域。可以定期进行重复测量以确定制剂减少发红和刺激的能力。
皮肤水分/水合分析:皮肤水分/水合受益可以通过利用Nova Dermal PhaseMeter进行的阻抗测量进行测量。阻抗计测量皮肤水分含量的变化。皮肤外层具有不同的电性质。当皮肤干燥时,其导电很差。当其变得更含水时,得到提高的导电性。因此,皮肤阻抗的变化(与导电性有关)可以用于评价皮肤水合的变化。可以根据仪器说明针对每个测试日进行校准装置。还可以对温度和相对湿度进行标记。对受试者可以进行如下评价:在测量前其可以在具有确定湿度(例如30%至50%)和温度(例如68℃至72℃)的室内进行平衡。在脸的每一侧读取3个独立的阻抗读数,记录和取平均。阻抗计可以使用T5设定,其对施用到脸上每5秒的阻抗值进行平均。变化可以以统计方差和显著性进行报道。根据该方法可以分析本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物。
皮肤清透度和减少雀斑与老年斑的分析:使用Minolta Chromometer评价皮肤清透度和减少雀斑与老年斑。肤色的变化可以使用Minolta Chroma Meter的a*值进行评价以确定由于产品处理引起刺激的可能性。a*值测量在红色区域肤色的变化。这用于确定本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物是否减少刺激。测量可以在脸的每一侧进行并取平均,作为左脸和右脸的值。皮肤清透度也可以使用Minolta Meter进行测量。测量是Minolta Meter的a*、b、和L值的组合,并与皮肤亮度有关,很好地对应于皮肤的光滑度和水合。如上进行皮肤读数。在一个非限制性方面,皮肤清透度可以描述为L/C,其中C是色度并定义为(a2+b2)1/2。
皮肤干燥、表面细纹、皮肤光滑度和肤色分析:皮肤干燥、表面细纹、皮肤光滑度和肤色可以用临床评分技术进行评价。例如,皮肤干燥的临床评分可以通过5分标准Kligman数值进行确定:(0)皮肤是柔软和滋润的;(1)皮肤呈现正常、没有可见的干燥;(2)皮肤触摸稍感干燥、没有可见的剥落;(3)皮肤感觉干燥、粗糙、具有一些鳞屑的发白外观;(4)皮肤感觉非常干燥、粗糙、具有鳞屑的发白外观。评价可以由两个临床医师独立进行并取平均。
肤色临床评分分析:肤色临床评分可以通过10分模拟数值实施:(10)平滑均匀、粉红棕色的皮肤。手持放大镜检查时没有暗沉、发红或有鳞屑的斑块。皮肤的微观纹理摸上去非常均匀;(7)不用放大镜观察到均匀的肤色。没有鳞状区域,但是由于色素淀积或红斑有些微疹斑。没有直径大于1cm的疹斑;(4)轻易地注意到皮肤疹斑和不均匀纹理两者。少量鳞屑。某些区域摸上去粗糙的皮肤;(1)不均匀的皮肤着色和纹理。多个区域的鳞屑和疹斑,或色素减退型、发红或黑色斑点。直径超过1cm的大面积不均匀着色。评价由两个临床医师独立进行并取平均。
皮肤平滑度临床评分分析:皮肤光滑度临床评分可以通过10分模拟数值进行分析:(10)光滑的,皮肤是滋润的和反光的,手指划过表面时没有阻力;(7)一定程度光滑的,微小阻力;(4)粗糙、明显改变的,摩擦时有摩擦力;(1)粗糙、易剥落的、不均匀的表面。评价由两个临床医师独立进行并取平均。
用Packman等人(1978)公开的方法分析皮肤光滑度和皱纹减少:皮肤光滑度和皱纹减少也可以通过使用Packman等人(1978)公开的方法进行可视化评价。例如,每位受试者就诊时,对每一受试者的表面面部线条(SFL)的深度、浅度和总数可以进行认真评分和记录。通过将数量因子乘以深度/宽度/长度因子得到数值分数。获得眼睛区域和嘴巴区域(左侧和右侧)的分数,加到一起作为总皱纹分数。
用Hargens Ballistometer进行皮肤紧实度分析:皮肤紧实度可以用HargensBallistometer进行测量,其是通过在皮肤上落下小物体并记录前两个反弹峰而评价皮肤弹性和紧实度的装置。Ballistometry是使用相对钝探头(4平方毫米-接触面积)的轻量小探测器。将探测器轻轻穿透到皮肤里,得到依赖于皮肤外层性质的测量,该皮肤外层包含角质层和外表皮以及部分真皮层。
用Gas Bearing Electrodynamometer分析皮肤柔软度/柔韧性:皮肤柔软度/柔韧性可以使用Gas Bearing Electrodynamometer进行评价,其是测量皮肤压力/张力性质的装置。皮肤的黏弹性与皮肤滋润有关。可以通过用双面胶将探针附着在皮肤表面实现对脸颊区域特定位点的测量。可以将大约3.5gm的力平行施加于皮肤表面,精确地测量皮肤位移。然后可以计算皮肤的柔韧性,并表达为DSR(动态弹簧刚度,以gm/mm计)。
用复制品分析线条和皱纹出现:皮肤上线条和皱纹出现可以使用复制品进行评价,该复制品是皮肤表面的印模。可以使用硅橡胶状材料。复制品可以通过图像分析进行分析。线条和皱纹的可见性变化可以通过利用硅复制品形成受试者脸并用计算机图像分析***分析复制品图像进行客观定量。复制品可以从眼睛区域和颈部区域获得,并用数码相机以低照明入射角进行拍摄。数字图像可以用图像处理程序进行分析并确定复制品被皱纹和细纹覆盖的区域。
用表面光度仪/记录针法分析皮肤表面轮廓:可以使用表面光度仪/记录针法进行测量皮肤表面轮廓。这包括闪光或拖动记录针穿过复制品表面。记录针的垂直位移可以通过远程传感器录入计算机,在扫描复制品一定长度后,皮肤轮廓的横截面分析可以以二维曲面产生。该扫描可以沿着固定轴重复任意次数以产生皮肤模拟3D图像。使用记录针技术可以获得复制品的10个随机截面,并组合以产生平均值。感兴趣的值包括Ra,其为通过积分相对于平均轮廓高度的轮廓高度计算得到的所有粗糙度(高度)值的算术平均数。Rt,其为最高峰和最低谷之间的最大垂直距离,Rz,其为平均峰振幅减去平均峰高度。数值以用mm为单位的校准值给出。在每次使用前,应通过扫描已知值的金属标准物使设备标准化。Ra值可以通过下式计算:Ra=标准化粗糙度;lm=横向(扫描)长度;y=轮廓位置相对于平均轮廓高度(x轴)的绝对值。
MELANODERMTM分析:在其他非限制性方面,本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物的功效可以使用皮肤类似物例如MELANODERMTM进行评价。当暴露于L-二羟苯基丙氨酸(L-DOPA)(黑色素前体)时,黑色素细胞肯定会染色,该黑色素细胞是皮肤类似物中的一种细胞。皮肤类似物MELANODERMTM可以用包含本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物的各种基质进行处理或将基质单独作为对照。或者,可以将未经处理的皮肤类似物样品用作对照物。
丝聚蛋白的产生:可以测量由于本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物引起的角质细胞中产生丝聚蛋白的变化。丝聚蛋白是皮肤中天然滋润因子(NMF)的前体。NMF增加会增加皮肤含水量。经处理的和未经处理的角质细胞中丝聚蛋白产生可以使用分析角质细胞裂解物中的丝聚蛋白浓度的生物分析确定。可以用来定量丝聚蛋白产生的生物分析的非限制性实例是SimonTM蛋白印迹分析。对于每个样品,正常人表皮角质细胞(NHEK)在Life Technologies的含钙EPI-200–Mattek生长培养基(M-EP-500-CA)中生长。在处理之前,NHEK在生长培养基中在37℃、在5%的CO2中培养过夜。然后将NHEK在含有1%的测试化合物/提取物或不含化合物/提取物(阴性对照)的生长培养基中培养24至36小时。然后可以洗涤NHEK、收集并储存在冰上或更冷处直到使用裂解缓冲液和超声在冰上裂解。可以确定样品的蛋白浓度和用于使样品归一化。裂解物可以储存在-80℃直到在定量分析中使用。
SimonTM蛋白印迹生物分析采用使用丝聚蛋白特异性抗体的定量蛋白印迹免疫分析技术而定量检测测试样品中的丝聚蛋白。将细胞样品裂解并归一化蛋白浓度。然后可以将归一化的样品和分子量标准品上样并在变性蛋白分离胶上跑毛细管电泳。将胶中的蛋白固定和使用丝聚蛋白特异性一级抗体免疫杂交。然后可以将固定的蛋白用结合一级抗体的酶联检测抗体免疫杂交。然后可以向固定的蛋白添加化学发光底物溶液,以使得化学发光显色与结合于固定中的丝聚蛋白量成比例。在特定时间终止化学发光显色,可以测量化学发光信号的强度并与阳性和阴性对照比较。
闭合蛋白的产生:可以测量由于本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物引起的角质细胞中产生闭合蛋白的变化。闭合蛋白是对形成紧密连接和皮肤水分屏障功能重要的蛋白。可以确定在经处理的或未经处理的角质细胞中怎样产生闭合蛋白的非限制性实例是通过使用分析角质细胞裂解物中的闭合蛋白浓度的生物分析。可以使用SimonTM蛋白印迹分析进行生物分析。对于样品,来自Life Technologies的成熟人表皮角质细胞(HEKa)(C-005-5C)可以在来自LifeTechnologies的含钙Epilife生长培养基(M-EP-500-CA)中在37℃、在5%的CO2中培养24小时,该培养基补充了Life Technologies的角质细胞生长补充物(HKGS)(S-101-5)。然后将HEKa在含有测试化合物/提取物的生长培养基中培养24至48小时,将不含化合物/提取物的生长培养基作为阴性对照,或含1mM CaCl2的生长培养基作为阳性对照。然后可以将NEKa洗涤、收集并储存在冰上或更冷处直到使用裂解缓冲液和超声在冰上裂解。可以确定样品的蛋白浓度和用于归一化样品。可以将裂解物储存在-80℃直到在生物分析中使用。
SimonTM蛋白印迹生物分析采用使用闭合蛋白特异性抗体的定量蛋白印迹免疫分析技术而定量检测测试样品中的闭合蛋白。将细胞样品裂解并归一化为蛋白浓度。然后将归一化的样品和分子量标准品上样并在变性蛋白分离胶中跑毛细管电泳。将胶中的蛋白固定和使用闭合蛋白特异性一级抗体免疫杂交。然后可以将固定的蛋白用结合一级抗体的酶联检测抗体免疫杂交。然后可以向固定的蛋白添加化学发光底物溶液,以使得化学发光显色与结合于固定中的闭合蛋白量成比例。在特定时间终止化学发光显色,可以测量化学发光信号的强度并与阳性和阴性对照比较。
角质细胞单层渗透性:可以测量由于本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物引起的角质细胞单层渗透性的变化。角质细胞单层渗透性是皮肤屏障完整性的测量。在经处理的和未经处理的角质细胞中的角质细胞单层渗透性可以使用Millipore体外血管渗透性分析(ECM642)作为一个非限制性实例来确定。该测试分析了内皮细胞吸收、转运和渗透。简言之,可以将Life Technologies的成熟人表皮角质细胞(C-005-5C)接种到收集孔内的多孔胶原蛋白覆盖膜上。然后将角质细胞在LifeTechnologies的含钙Epilife生长培养基(M-EP-500-CA)中在37℃、在5%CO2中培养24小时,该培养基补充了Life Technologies的角质细胞生长补充物(HKGS)(S-101-5)。该培养时间使得细胞形成单层并闭合膜孔。然后用含有(测试样品)或不含(未经处理的对照)测试化合物/提取物的新鲜培养基替换培养基,将角质细胞在37℃和5%的CO2下再培养48小时。为了确定含/不用含试化合物/提取物培养后的角质细胞的单层渗透性,用含高分子量异硫氰酸荧光素(FITC)-右旋糖酐的新鲜培养基替换培养基,将角质细胞在37℃和5%CO2下培养4小时。在4小时培养期间,FITC可以以与单层渗透性成比例的速度穿过角质细胞单层和多孔膜进入收集孔。培养4小时后,可以确定细胞活力和收集孔中的FITC含量。对于FITC含量,收集收集孔中的培养基,当在520nm激发时,确定480nm处的培养基荧光性(Em)。与未经处理的对照相比,可通过以下等式确定渗透性百分比和变化百分比:渗透百分比=((测试样品的平均Ex/Em)/(未经处理对照的平均Ex/Em)*100;变化百分比=测试样品的渗透百分比-未经处理对照的渗透百分比。
透明质酸的产生:可以测量由于本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物引起的人真皮成纤维细胞中产生透明质酸的变化。HA是涉及基质结构稳定和参与提供组织和细胞膨胀压的多糖。作为一个非限制性实例,使用R&DSystems的Hyaluronan DuoSet ELISA试剂盒(DY3614)可以确定经处理的或未经处理的成熟人真皮成纤维细胞(HDFa)中的HA产生。在该分析中,对于样品的产生,在处理前,将Cascade Biologics的亚融合HDFa细胞(C-13-5C)在饥饿培养基(在杜氏改良的Eagle培养基中含0.15%胎牛血清和1%的青霉素链霉素溶液)中、在37℃和10%CO2中培养72小时。然后用含测试化合物、阳性对照(Sigma-Aldrich的佛波醇12-豆蔻酸酯13-醋酸酯(P1585)和Sigma-Aldrich的血小板衍化生长因子(P3201))或无添加剂的新鲜饥饿培养基培养细胞24小时。然后收集培养基并在-80℃冷冻直至用在ELISA分析中。
简言之,ELISA分析采用定量夹心酶免疫分析技术,通过将HA特异性捕获抗体预覆盖在微孔板上。将经处理细胞和未经处理细胞的标准品和培养基移液至微孔板使得任何存在的HA与固定的抗体结合。在洗去未结合物质之后,将HA特异性酶联检测抗体添至孔中。然后洗涤去除任何未结合的抗体-酶反应物,向孔中添加底物溶液以使得能够进行与初始步骤中结合的HA量成比例显色。在特定时间终止显色,使用微孔板读板器测量450nm处的颜色强度。
透明质酸酶活性的抑制:可以测量由于本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物引起的透明质酸酶活性的变化。透明质酸酶是降解HA的酶。HA是参与基质结构稳定和参与提供组织和细胞膨胀压的多糖。作为一个非限制性实例,透明质酸酶活性可以使用由Sigma-Aldrich操作规程#EC 3.2.1.35改进的体外操作规程确定。简言之,将Sigma-Aldrich的透明质酸酶1-S型(H3506)添加至包含测试化合物或对照的微板反应孔。将单宁酸用作阳性对照抑制剂,对照酶可以不添加测试化合物,含有测试化合物或阳性对照而不含透明质酸酶的孔可以用作背景阴性对照。在添加底物(HA)之前,将孔在37℃培养10分钟。添加底物,使反应在37℃培养45分钟。然后将每个反应溶液的一部分转移至pH3.75的醋酸钠和醋酸溶液并缓慢混合以终止反应部分(终止孔)。在添加部分反应溶液至终止孔之后,终止孔和反应孔都应该含有相同体积的溶液。将反应孔和终止孔都在室温下培养10分钟。然后测量反应孔和终止孔两者在600nm的吸收值。可以使用以下公式计算抑制:抑制(或对照)活性=(抑制剂终止孔在600nm的吸光度-抑制剂反应孔在600nm的吸光度);初始活性=对照酶在600nm的吸光度;抑制百分比=[(初始活性/抑制剂活性)*100]-100。
过氧化物酶体增殖物激活受体γ(PPAR-γ)活性:可以测量由于本说明书所公开的每种活性成分、该成分的任一组合或具有所述组合的组合物引起的PPAR-γ活性的变化。PPAR-γ是对产生皮脂的重要受体。作为一个非限制性实例,PPAR-γ的活性可以使用分析测试化合物或组合物抑制配体结合能力的生物分析确定。简言之,荧光小分子pan-PPAR配体,可以将从Life Technologies商购的FLUORMONETM Pan-PPAR Green(PV4894)用于确定测试化合物或组合物是否能够抑制配体结合至PPAR-γ。样品孔包含PPAR-γ和荧光配体和下列之一:测试化合物或组合物(测试);参考抑制剂;罗格列酮(阳性对照);或不含测试化合物(阴性对照)。将孔培养一段时间以使得配体有结合PPAR-γ的机会。然后可以测量每个样品孔的荧光极化,并与对照孔比较以确定测试化合物或组合物的抑制百分比。
细胞因子分析:将人表皮胶质细胞培养至70%至80%融合。将平板中的培养基吸出,并添加0.025%的胰蛋白酶/EDTA。当细胞变圆时,轻拍培养皿以释放细胞。将包含胰蛋白酶/EDTA的细胞从培养皿移出并中和。将细胞在180×g离心5分钟以形成细胞团块。吸去上清。将得到的团块在EpiLifeTM培养基(Cascade Biologics)中重悬。以大约10%至20%的融合将细胞接种至6孔板。当细胞变成约80%的融合后,吸去培养基,添加1.0ml的EpiLifeTM以及佛波醇13-豆蔻酸12-乙酸酯(“PMA”)(已知的炎症诱导剂),将测试组合物稀释液加至2个复制孔(即1.0%(100μl的100×储备液)和0.1%(的100×储备液),将测试组合物稀释到终体积1ml的EpiLife生长培养基中)。将培养基缓慢旋转以保证充分混合。另外,添加1.0ml的EpiLifeTM至对照孔,其含有或不含有附加PMA。在进料后,然后将平板在37±1℃和5.0±1%CO2下培养大约5小时。在该5小时培养后,将全部培养基收集至锥形管中并冷冻于-70℃。
为了分析,用16格抗细胞因子抗体加实验对照(Whatman BioSciences)将16格杂交盒附接至3个重复阵列的16格FAST片,将载玻片置于FAST框中(每个框4个载玻片)用于处理。在室温下用70ml的S&S蛋白阵列封闭缓冲液(Whatman Schleicher and Scheull)将阵列封闭15分钟。去除封闭缓冲液并添加70ml每种上清样品至每个阵列。将阵列在室温下伴随缓慢搅动培养3小时。用TBS-T洗涤阵列3次。用70ml抗体混合物处理阵列,该抗体混合物包含对应于每个阵列捕获抗体的一种生物素化抗体。将阵列在室温下伴随缓慢搅动培养1小时。用TBS-T洗涤阵列3次。用70ml溶液在室温下伴随缓慢搅动培养阵列1小时,该溶液包含链霉亲和素-Cy5共轭物。用TBS-T洗涤阵列3次,在去离子水中快速冲洗并干燥。
载玻片可以在Perkin-Elmer ScanArray 4000共聚荧光成像***中成像。可以保存阵列图像,用Imaging Research ArrayVision软件分析。简言之,点强度通过减去背景信号而确定。可以将每个样品条件的点重复值取平均,然后与适合的对照对比。
内皮细胞管形成:内皮细胞管形成参与血管再生和微血管毛细管形成。毛细管形成和血管再生可能有助于皮肤发红或痤疮。利用在细胞培养体系中预形成的初始人脐静脉内皮细胞(HUVEC)使用毛细管小管破坏试验可以确定在存在或不存在测试提取物时内皮细胞形成小管的能力。
简言之,在Extracellular Matrix上体外培养HUVEC,Extracellular Matrix刺激血管内皮细胞的粘附和管形成以形成毛细血管样内腔结构。这些在体外形成的毛细管在很多方面类似于人血管毛细管。毛细管分析基于这种现象,用于评价潜在的脉管靶向剂。
HUVEC培养在5%CO2、37℃细胞培养箱中生长。HUVEC的完全生长培养基是内皮细胞基础培养基(EBM),其补充了2%胎牛血清(FBS)、12μg/ml胎牛脑提取物、1μg/ml氢化可的松和1μg/ml GA-1000(庆大霉素-两性霉素B)。通道3至8之间的HUVEC培养物可以用于全部分析实验。
HUVEC用荧光剂Calcein AM预先标记,并接种在Extracellular Matrix覆盖的、具有其完全培养基的96孔培养板中。形态发生过程约4小时后,应该形成内皮细胞毛细小管。然后,将50μl体积的设计剂量测试试剂应用到形成的毛细小管培养物中作为处理状态。未处理的对照可以添加测试试剂的载剂。FDA批准的抗血管生成药索坦(Sutent)可以包含一个浓度作为分析性能对照。处理约6小时后,通过显微镜检查每个孔中的内皮细胞小管形态,成像,可以定量分析处理条件下的毛细管破坏活性。每种测试条件可以在多个孔中进行,包括对照。
本文中所公开和要求保护的所有组合物和/或方法可以根据本公开无需过度实验即可完成和实现。尽管本发明的组合物和方法已经按照优选实施方案进行描述,但是对于本领域技术人员明显的是,可以对本文所描述的组合物和/或方法以及方法的步骤或步骤顺序应用变化,而不脱离本发明的概念、精神和范围。更具体地,明显的是化学和生理都相关的某些试剂可以替代本文所描述的试剂,同时会实现相同或相似的结果。对本领域技术人员明显的所有这类相似替代和改变都视为在如所附权利要求限定的本发明的精神、范围和概念内。
参考文献
以下参考文献一定程度上提供本文所述细节的示例性流程或其他补充细节,其通过引用明确地并入本文。
化妆品成分词典,第三版,CTFA,1982
国际化妆品成分词典,第四版,CTFA,1991
国际化妆品成分词典和手册,第十版,CTFA,2004
国际化妆品成分词典和手册,第十二版,CTFA,2008
Claims (20)
1.一种使皮肤去角质、使皮肤和/或毛发清洁、使皮肤光滑、使皮肤和/或毛发滋润、使干燥皮肤舒缓和/或使皮肤软化的方法,所述方法包括将局部用组合物应用于皮肤和/或毛发,所述局部用组合物包含牛油果脂、PEG-50牛油果脂和水合硅石中的一种或更多种,其中使皮肤去角质、使毛发和/或皮肤清洁、使皮肤光滑、使皮肤和/或毛发滋润、使皮肤舒缓和/或使皮肤软化。
2.根据权利要求1所述的方法,其中所述组合物包含0.1重量%至10重量%的牛油果脂、0.1重量%至5重量%的PEG-50牛油果脂和/或1重量%至10重量%的水合硅石。
3.根据权利要求1所述的方法,其中所述组合物包含水合硅石,还包含水、月桂醇硫酸酯TEA盐和椰油酰胺丙基甜菜碱。
4.根据权利要求3所述的方法,其中所述组合物还包含丙烯酸酯共聚物、氯化钠、羟乙基纤维素、三乙醇胺、丙二醇、氢化霍霍巴油、对羟基苯甲酸甲酯和EDTA二钠。
5.根据权利要求4所述的方法,其中所述组合物还包含柠檬酸、和/或杏籽粉和桃籽粉的组合。
6.根据权利要求3所述的方法,其中所述组合物包含PEG-50牛油果脂和水合硅石,还包含三乙醇胺、丙烯酸酯/C10-30丙烯酸烷基酯交联聚合物、苯氧乙醇、辛甘醇、氯化钠、EDTA二钠、乙基己基甘油和己二醇。
7.根据权利要求6所述的方法,其中所述组合物还包含氢化霍霍巴油、聚山梨醇酯20和硬脂醇硬脂酸酯的组合、和/或刺梨提取物。
8.根据权利要求1所述的方法,其中所述组合物包含牛油果脂,还包含水、鲸蜡硬脂醇、硬脂酸甘油酯、聚丙烯酸酯-13、聚异丁烯、聚山梨醇酯20、甘油、丙二醇、葵花籽油和红花籽油。
9.根据权利要求8所述的方法,其中所述组合物还包含PEG-100硬脂酸酯、苯氧乙醇、丙二醇、杏仁油、聚二甲基硅氧烷、辛甘醇、醋酸生育酚、黄原胶、EDTA二钠和乙基己基甘油。
10.根据权利要求1所述的方法,其中将所述组合物配制为乳液。
11.一种局部用组合物,其包含牛油果脂、PEG-50牛油果脂和水合硅石中的一种或更多种,其中所述组合物能够使皮肤去角质、使皮肤和/或毛发清洁、使皮肤光滑、使皮肤和/或毛发滋润、使皮肤舒缓和/或使皮肤软化。
12.根据权利要求11所述的组合物,其包含0.1重量%至10重量%的牛油果脂、0.1重量%至5重量%的PEG-50牛油果脂和/或1重量%至10重量%的水合硅石。
13.根据权利要求11所述的组合物,其包含水合硅石,还包含水、月桂醇硫酸酯TEA盐和椰油酰胺丙基甜菜碱。
14.根据权利要求13所述的组合物,其还包含丙烯酸酯共聚物、氯化钠、羟乙基纤维素、三乙醇胺、丙二醇、氢化霍霍巴油、对羟基苯甲酸甲酯和EDTA二钠。
15.根据权利要求14所述的组合物,其还包含柠檬酸、和/或杏籽粉和桃籽粉的组合。
16.根据权利要求13所述的组合物,其包含PEG-50牛油果脂和水合硅石,还包含三乙醇胺、丙烯酸酯/C10-30丙烯酸烷基酯交联聚合物、苯氧乙醇、辛甘醇、氯化钠、EDTA二钠、乙基己基甘油和己二醇。
17.根据权利要求16所述的组合物,其还包含氢化霍霍巴油、聚山梨醇酯20和硬脂醇硬脂酸酯的组合、和/或刺梨提取物。
18.根据权利要求11所述的组合物,其包含牛油果脂,还包含水、鲸蜡硬脂醇、硬脂酸甘油酯、聚丙烯酸酯-13、聚异丁烯、聚山梨醇酯20、甘油、丙二醇、葵花籽油和红花籽油。
19.根据权利要求18所述的组合物,其还包含PEG-100硬脂酸酯、苯氧乙醇、丙二醇、杏仁油、聚二甲基硅氧烷、辛甘醇、醋酸生育酚、黄原胶、EDTA二钠和乙基己基甘油。
20.根据权利要求11所述的组合物,其中所述组合物被配制为乳液。
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2016
- 2016-12-27 WO PCT/IB2016/058024 patent/WO2017115280A1/en unknown
- 2016-12-27 EP EP16881372.3A patent/EP3397239A4/en active Pending
- 2016-12-27 US US15/390,828 patent/US10206868B2/en active Active
- 2016-12-27 KR KR1020187021958A patent/KR20180089552A/ko not_active Application Discontinuation
- 2016-12-29 CN CN201611242543.XA patent/CN107028808A/zh active Pending
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2019
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CN111246888A (zh) * | 2017-10-20 | 2020-06-05 | 日本乐敦制药株式会社 | 皮肤障碍改善用组合物 |
CN111278415A (zh) * | 2017-11-07 | 2020-06-12 | 株式会社爱茉莉太平洋 | 泡沫型染发剂组合物 |
CN111278415B (zh) * | 2017-11-07 | 2023-02-17 | 株式会社爱茉莉太平洋 | 泡沫型染发剂组合物 |
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EP3397239A1 (en) | 2018-11-07 |
US20240000673A1 (en) | 2024-01-04 |
US11642289B2 (en) | 2023-05-09 |
KR20180089552A (ko) | 2018-08-08 |
WO2017115280A1 (en) | 2017-07-06 |
US11925700B2 (en) | 2024-03-12 |
US20210322286A1 (en) | 2021-10-21 |
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US10206868B2 (en) | 2019-02-19 |
US10952948B2 (en) | 2021-03-23 |
US20190240139A1 (en) | 2019-08-08 |
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