CN105188662A - 化妆品组合物 - Google Patents
化妆品组合物 Download PDFInfo
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- CN105188662A CN105188662A CN201480014775.2A CN201480014775A CN105188662A CN 105188662 A CN105188662 A CN 105188662A CN 201480014775 A CN201480014775 A CN 201480014775A CN 105188662 A CN105188662 A CN 105188662A
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Abstract
公开了能够处理瘙痒的组合物及其使用方法,该组合物包含紫松果菊提取物、水飞蓟提取物、甘油以及包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物中的一种或更多种的组合。
Description
相关申请的交叉引用
本申请要求2013年3月14日提交的美国临时专利申请第61/784564号和2013年4月26日提交的美国临时专利申请第61/816286号的权益。所参考申请的内容通过引用并入本申请。
背景技术
A.技术领域
本发明一般涉及能够用于处理皮肤症状的方法和组合物。更具体地,本发明涉及局部护肤组合物,其包含来自紫松果菊(Echinaceapurpurea)的提取物、来自水飞蓟(silybummarianum)的提取物、甘油和/或包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(brassicacampestris)(油菜籽)甾醇的混合物,以及涉及使用这样的组合物处理瘙痒皮肤、干燥皮肤或红斑皮肤的方法。
B.相关技术说明
瘙痒或痒定义为引起抓挠的冲动的令人不悦的皮肤感觉。其可以是局部的或非局部的,并且可以作为急性症状或慢性症状存在。痒可能难以处理和无法处理,并且对诊断和治疗带来挑战。这种感觉的根本原因是由于表皮和真皮上层中的神经纤维的活性引起的。例如,干燥皮肤会活化这些神经纤维,这引起皮肤瘙痒的感觉,其通常伴随着抓挠。然而,抓挠会导致皮肤刺激或红斑、现有皮肤症状(例如,干燥皮肤,如脂溢性皮炎、特应性湿疹、接触性皮炎或干燥性湿疹)的扩散以及整体不美观的或视觉上令人不悦的皮肤外观。干燥皮肤甚至会导致细纹和皱纹。
解决瘙痒症状的组合物是已知的。然而,这类组合物不能既处理瘙痒皮肤又处理瘙痒皮肤的原因。
发明内容
本发明人已发现成分的组合可以作为抗瘙痒剂用于局部皮肤用制剂,同时还处理瘙痒皮肤/皮肤瘙痒的根本原因(例如干燥皮肤)。在这个意义上,组合可以说是具有双重效果:(1)处理瘙痒皮肤;和(2)处理瘙痒皮肤的原因,所述原因可以是干燥皮肤。该双重效果的益处是仅需要一种组合物来有效地处理和预防瘙痒皮肤和干燥皮肤。“干燥皮肤”或“干皮病”包括(与正常皮肤相比)具有减少的水分的皮肤,其会导致瘙痒皮肤、具有薄片的皮肤(“片状皮肤”)、具有鳞片的皮肤(“鳞状皮肤”)或具有皲裂的皮肤。干燥皮肤的实例包括脂溢性皮炎、特应性湿疹、接触性皮炎或干燥性湿疹。
在一个实施方案中,公开了一种组合物,其包含来自紫松果菊的提取物、来自水飞蓟的提取物、甘油和/或包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。在一些实施方案中,公开了局部护肤组合物,所述组合物包含皮肤病学上可接受的载体和以下成分的组合:紫松果菊提取物、水飞蓟提取物、甘油以及包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。在一些实施方案中,组合物活化皮肤中的2型人类大麻素受体和/或抑制皮肤中的脂肪酸酰胺水解酶活性。
来自紫松果菊的提取物和/或来自水飞蓟的提取物可以是水提取物、醇提取物、水-醇提取物或基于油的提取物。在一些实施方案中,紫松果菊提取物是水提取物。在一些实施方案中,水飞蓟提取物是水提取物。来自紫松果菊的提取物和/或来自水飞蓟的提取物可以来自全株、叶、种子、花、茎或根。在一些实施方案中,紫松果菊提取物来自全株。在一些实施方案中,水飞蓟提取物来自果实。
该组合物还可以包含保湿剂、紫外吸收剂、抗氧化剂、结构化剂、乳化剂、含硅酮的化合物、精油、增稠剂和/或防腐剂,例如本说明书全文中所公开的那些。该组合物可以包含药物成分,例如本说明书全文中所公开的那些。组合物可以包含0.0001重量%至10重量%(或0.001重量%、0.01重量%、0.1重量%、1重量%、2重量%、3重量%、4重量%、5重量%、6重量%、7重量%、8重量%、9重量%或10重量%或更多)的紫松果菊提取物、0.0001重量%至10重量%(或0.001重量%、0.01重量%、0.1重量%、1重量%、2重量%、3重量%、4重量%、5重量%、6重量%、7重量%、8重量%、9重量%或10重量%或更多)的水飞蓟提取物、0.0001重量%至10重量%(或0.001重量%、0.01重量%、0.1重量%、1重量%、2重量%、3重量%、4重量%、5重量%、6重量%、7重量%、8重量%、9重量%或10重量%或更多)的甘油、和/或0.0001重量%至10重量%(或0.001重量%、0.01重量%、0.1重量%、1重量%、2重量%、3重量%、4重量%、5重量%、6重量%、7重量%、8重量%、9重量%或10重量%或更多)的包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。在一些实施方案中,组合物包含约0.50重量%的紫松果菊提取物、约1.0重量%的水飞蓟提取物和约2.0重量%的包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。在一些实施方案中,组合物包含15重量%的甘油。
还公开了一种处理瘙痒的方法,其包括对需要处理的皮肤局部施用本说明书全文所公开的组合物中的任一种,其中对需要处理的皮肤进行局部施用来处理瘙痒。瘙痒或痒定义为引起抓挠的欲望的令人不悦的感觉。其可能与大量疾病相关,包括但不限于干燥皮肤和红斑皮肤。除了处理瘙痒之外,组合物还可以同时处理干燥皮肤。在另一实施方案中,公开了一种减轻与瘙痒相关的症状的方法,其包括对有此需要的皮肤局部施用本说明书全文所公开的组合物中的任一种,其中所述组合物的局部施用减轻与瘙痒相关的症状。组合物可以施用至瘙痒皮肤、红斑皮肤或干燥皮肤。在一些实例中,可以通过将本发明的组合物局部施用至细纹和/或皱纹来使用所述组合物处理细纹和皱纹。
在特定的方面,组合物施用至皮肤,并且在局部施用后在皮肤上保留至少5、10、15、30或更多分钟,或者1、4、8、12、16、20或24小时。组合物可以施用至瘙痒皮肤、红斑皮肤或干燥皮肤,或者存在于面部皮肤、腿部皮肤、踝部皮肤、臂部皮肤、手部皮肤和/或头皮皮肤上的脂溢性皮炎。
还公开了一种处理或减轻瘙痒症状的方法,其包括对瘙痒皮肤局部施用包含以下组分的组合物:(a)紫松果菊提取物和水飞蓟提取物,其中所述提取物的组合在所述瘙痒皮肤中活化2型人类大麻素受体并抑制脂肪酸酰胺水解酶活性;和(b)甘油和包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物,其中甘油和所述包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物的组合使所述瘙痒皮肤湿润。
本发明的组合物可以配制为局部护肤组合物。组合物可以是化妆品组合物。在其它方面,组合物可以包含在化妆品载体中。化妆品载体的非限制性实例在本说明的其它章节中公开,并且对于本领域技术人员是已知的。化妆品载体的实例包括乳液(例如水包油乳液和油包水乳液)、乳霜、润肤露、溶液(例如水溶液或水-醇溶液)、无水基质(例如口红或粉末)、凝胶和软膏。在特定的方面,组合物可以配制为乳霜、凝胶或润肤露。在一些实例中,组合物为乳液(例如水包油、油包水、疏水包亲水、亲水包疏水、水包硅酮、硅酮包水等)。
组合物还可以配制用于在使用期间每天局部皮肤施用至少1、2、3、4、5、6、7或更多次。在本发明的其它方面中,组合物可以是储存稳定或颜色稳定的,或是两者。还期望可以选择组合物的黏度以达到期望的结果,例如根据期望的组合物类型,该组合物的黏度可以从1cps到远超过1百万cps,或是其间可得到的任意范围或整数(例如,在25℃下在使用TC轴的布氏黏度计上以2.5rpm的转速测量的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)。在非限制性方面中,组合物可以具有大约6至大约9的pH值。在其它方面,pH可以是1、2、3、4、5、6、7、8、9、10、11、12、13或14。本发明的组合物可以具有UVA和UVB吸收性能。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、或其间可得到的任意范围或整数的防晒指数(SPF)。组合物可以是防晒的润肤露、喷雾或乳霜。在具体的方面,组合物可以是无油的、基本上无水的和/或无水的。其它方面包括具有水的组合物。
本发明的组合物还可以包含以下附加成分中的任一种、任意组合或全部:水、螯合剂、保湿剂、防腐剂、增稠剂、含硅酮的化合物、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,组合物可以包含在前文中列举的这些附加成分中的至少二、三、四、五、六、七、八、九、十种或全部。这些附加成分的非限制性实例在本说明书全文列出,并通过引用并入本章节。这类成分的量的范围以组合物的重量或体积计可以为0.0001%至99.9%,或者是在如本说明书其它章节中所公开的范围之间的任意整数或范围,其通过引用并入本段。
另外,组合物还可以用于处理或预防多种其他皮肤症状。例如,组合物可以用于处理或预防细纹或皱纹、红斑、敏感性皮肤或发炎的皮肤。在具体的方面,红斑、敏感性皮肤或发炎的皮肤是由皮肤晒伤、皮肤的电处理、皮肤烧伤、接触性过敏、全身性过敏、皮肤中毒、运动、昆虫叮咬、细菌感染、病毒感染、真菌感染、原生动物感染、按摩或风吹性皮肤伤导致的。在其它方面,以下另外的皮肤症状可以根据本说明书和权利要求书全文所公开的方法和组合物来处理或预防:瘙痒症、雀斑、蜘蛛状血管病、老年斑、老年性紫癜、角化病、黄褐斑、疹块、结节、晒伤皮肤、皮炎(包括但不限于脂溢性皮炎、钱币形皮炎、接触性皮炎、过敏性皮炎、剥脱性皮炎、口周皮炎和停滞性皮炎)、银屑病、毛囊炎、酒渣鼻、痤疮、脓疱病、丹毒、红癣、湿疹和其它炎性皮肤症状。在一些非限制性方面,皮肤症状可以是由暴露于紫外线、衰老、刺激、长期日照、环境污染、空气污染、风、寒冷、高温、化学品、疾病病理、烟熏或营养不良导致的。皮肤可以是面部皮肤或非面部皮肤(例如手臂、腿、手、胸、后背、脚等)。方法还可以包括确定需要皮肤处理的个体。个体可以是男性或女性。个体的年龄可以是至少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,或者其中可得出的任意范围。方法还可以包括局部施用对以下有效的量:提高皮肤的角质层更新速率;增加成纤维细胞中的胶原蛋白合成;提高细胞的抗氧化防御机制(例如抗氧化剂的外源性添加可以支撑、补充或者预防细胞抗氧化剂,例如皮肤细胞(例如角化细胞、黑色素细胞、朗格汉斯细胞等)中的过氧化氢酶和谷胱甘肽的损失,所述抗氧化剂会减少或预防对皮肤、细胞、蛋白质和脂质的氧化损伤);抑制黑色素细胞中的黑素生成;减少或预防对皮肤的氧化损伤(包括减少皮肤中脂质过氧化物的量和/或蛋白氧化)。
还预期包含本说明书和权利要求全文所公开的组合物中的任何一种的试剂盒。在特定的实施方案中,组合物包含在容器中。容器可以是瓶子、分配器或包装。容器可以分配预定量的组合物。在特定的方面,组合物以喷雾、团块或液体分配。容器可以在其表面上包含标记。标记可以是单词、缩写、图片或符号。
还预期一种包含本发明的组合物的产品。在非限制性方面,产品可以是化妆品。化妆品可以是本说明书其它章节所述的那些,或是本领域技术人员已知的那些。产品的非限制性实例包括保湿霜、乳霜、润肤露、柔肤剂、粉底、晚霜、口红、洗面乳、爽肤水、防晒霜、面膜、或抗老化产品。
还公开了本发明的以下实施方案1至33。实施方案1是一种用于处理瘙痒的方法,其包括对有此需要的皮肤局部施用组合物,所述组合物包含有效量的紫松果菊提取物、水飞蓟提取物、甘油以及包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物,其中所述组合物的局部施用处理瘙痒。实施方案2是实施方案1所述的方法,其中所述组合物活化皮肤中的2型人类大麻素受体并且抑制皮肤中的脂肪酸酰胺水解酶活性。实施方案3是实施方案1至2中任一项所述的方法,其中所述紫松果菊提取物是水提取物。实施方案4是实施方案1至3中任一项所述的方法,其中所述紫松果菊提取物来自全株。实施方案5是实施方案1至4中任一项所述的方法,其中所述水飞蓟提取物是水提取物。实施方案6是实施方案1至5中任一项所述的方法,其中所述水飞蓟提取物来自果实。实施方案7是实施方案1至6中任一项所述的方法,其中所述组合物配制为乳霜、润肤露、乳液、精华或洗面乳。实施方案8是实施方案1至7中任一项所述的方法,其中所述组合物是水包油乳液或油包水乳液。实施方案9是实施方案1至8中任一项所述的方法,其中有效量是0.001重量%至10重量%的紫松果菊提取物、0.001重量%至10重量%的水飞蓟提取物和0.001重量%至10重量%的包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。实施方案10是实施方案9所述的方法,其中有效量是0.50重量%的紫松果菊提取物、1.0重量%的水飞蓟提取物和2.0重量%的包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。实施方案11是实施方案10所述的方法,其中有效量是15重量%的甘油。实施方案12是实施方案1至9中任一项所述的方法,其中皮肤是瘙痒皮肤、干燥皮肤或红斑皮肤。实施方案13是实施方案1至12中任一项所述的方法,其中将所述组合物施用至皮肤,并在局部施用后在皮肤上保留至少5分钟。实施方案14是实施方案1至13中任一项所述的方法,其中需要处理的皮肤是面部皮肤、腿部皮肤、踝部皮肤、臂部皮肤手部皮肤或头皮皮肤。实施方案15是实施方案1至14中任一项所述的方法,其中所述组合物还包含保湿剂、紫外吸收剂、抗氧化剂、结构化剂、乳化剂、含硅酮的化合物、精油、增稠剂和防腐剂中的至少一种。实施方案16是实施方案1至15中任一项所述的方法,其中所述组合物还包含药物成分。实施方案17是一种用于减轻与瘙痒相关的症状的方法,其包括对有此需要的皮肤局部施用组合物,所述组合物包含有效量的紫松果菊提取物、水飞蓟提取物以及包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物,其中所述组合物的局部施用减轻与瘙痒相关的症状。实施方案18是一种处理瘙痒的方法,其包括对瘙痒皮肤局部施用包含以下组分的组合物:紫松果菊提取物和水飞蓟提取物,其中所述提取物的组合在所述瘙痒皮肤中活化2型人类大麻素受体并抑制脂肪酸酰胺水解酶活性;和甘油和包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物,其中甘油和所述包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物的组合使所述瘙痒皮肤湿润。实施方案19是一种局部护肤组合物,所述组合物包含皮肤病学上可接受的载体和以下成分的组合:紫松果菊提取物、水飞蓟提取物、甘油以及包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。实施方案20是实施方案19所述的局部护肤组合物,其中所述紫松果菊提取物是水提取物。实施方案21是实施方案19至20中任一项所述的局部护肤组合物,其中所述紫松果菊提取物来自全株。实施方案22是实施方案19至21中任一项所述的局部护肤组合物,其中所述水飞蓟提取物是水提取物。实施方案23是实施方案19至22中任一项所述的局部护肤组合物,其中所述水飞蓟提取物来自果实。实施方案24是实施方案19至23中任一项所述的局部护肤组合物,其中所述组合物还包含保湿剂、紫外吸收剂、抗氧化剂、结构化剂、乳化剂、含硅酮的化合物、精油、增稠剂和防腐剂中的至少一种。实施方案25是实施方案19至24中任一项所述的局部护肤组合物,其中所述组合物还包含药物成分。实施方案26是实施方案19至25中任一项所述的局部护肤组合物,其中所述组合物配制为乳霜、润肤露、凝胶或精华。实施方案27是实施方案19至26中任一项所述的局部护肤组合物,其中所述组合物是水包油乳液或油包水乳液。实施方案28是实施方案19至27中任一项所述的局部护肤组合物,其中所述组合物包含0.001重量%至10重量%的每种成分或成分的组合。实施方案29是实施方案28所述的方法,其中有效量是0.50重量%的紫松果菊提取物、1.0重量%的水飞蓟提取物和2.0重量%的包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。实施方案30是实施方案29所述的方法,其中有效量是15重量%的甘油。实施方案31是实施方案19至28中任一项所述的局部护肤组合物,其中所述组合物活化皮肤中的2型人类大麻素受体。实施方案32是实施方案19至31中任一项所述的局部护肤组合物,其中所述组合物抑制皮肤中的脂肪酸酰胺水解酶活性。实施方案33是实施方案19至28中任一项所述的局部护肤组合物,其中所述组合物活化皮肤中的2型人类大麻素受体并抑制皮肤中的脂肪酸酰胺水解酶活性。
组合物及其使用方法可以“包含”任何说明书全文所公开的成分,“主要由所述成分组成”或“由所述成分组成”。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。
“主要由……组成”意味着在组合物中包含附加成分不实质影响组合物作为抗瘙痒剂和用于处理干燥皮肤、片状皮肤、皲裂皮肤的有益性能。例如,如果组合物“主要由以下成分组成”:紫松果菊提取物、水飞蓟提取物、甘油以及包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物中的任一种、任意组合、或者2、3或全部4种,则所述组合物不包含实质影响组合物用于处理皮肤瘙痒、或干燥皮肤、片状皮肤、皲裂皮肤的有益性能的任何成分。例如,可能刺激皮肤、或造成皮肤干燥、或造成皮肤的痒感觉的成分会被排除。
期望的是,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。“可药用的”和/或“可化妆用的”描述具有令皮肤感觉舒适的特定的触觉性能的组合物(例如,不是太水或太油的组合物、具有丝滑质地的组合物、非黏性或非黏着的组合物等)。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。
“局部施用”是指将组合物施用或涂敷到角质组织的表面上。“局部皮肤用组合物”包含适合在角质组织上局部施用的组合物。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后明显的滴落或淤积。
“角质组织”包含配置作为哺乳类最外保护层的含有角质的层,并且包括但不限于皮肤、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的但不一定全部的所指定的事物,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。
当在权利要求和/或说明书中使用时,术语“抑制”、“减少”、“处理”或这些术语的任何变体包括达到预期结果的任何可测量的减少或完全的抑制。
作为本说明书和/或权利要求所使用的术语,术语“有效的”表示适于实现希望的、期望的或预期的结果。
本发明的其它目的、特征和优点通过下面的详细描述会变得明显。然而,应理解详细的描述和实施例在表明本发明的具体实施方案时仅以举例说明给出。另外,期望的是通过该详细描述,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
痒感觉一般限于皮肤和邻接的粘膜区域。然而,抓挠会导致皮肤刺激或红斑、现有皮肤症状(例如,干燥皮肤,如脂溢性皮炎、特应性湿疹、接触性皮炎或干燥性湿疹)的扩散以及整体不美观的或视觉上令人不悦的皮肤外观。干燥皮肤甚至会导致细纹和皱纹。
这种感觉的根本原因是由于表皮和真皮上层中的神经纤维的活性。例如,干燥皮肤会活化这些神经纤维,这引起皮肤瘙痒的感觉,其通常引起抓挠。1型大麻素受体(CBr1)和2型大麻素受体(CBr2)位于表皮中。CBr2受体是由CNR2基因编码的G蛋白偶联的受体。一些大麻素激动剂可能能够抑制组胺引起的皮肤发痒。另外,大麻素受体的局部激动剂在特应性湿疹和尿毒症瘙痒中可以具有抗瘙痒的作用。
代替使用多种组合物来处理瘙痒皮肤和干燥皮肤,本发明人发现了可以并入到局部组合物中的成分的独特组合用于同时处理两种皮肤症状。如前所述,该组合包括紫松果菊提取物、水飞蓟提取物、甘油和/或包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物的组合。发现紫松果菊提取物在体内与2型人类大麻素受体(CBr2)结合,这活化了CBr2,并且发现水飞蓟提取物抑制脂肪酸酰胺水解酶(FAAH)活性。已知FAAH破坏大麻素,这进而会活化CBr2。本发明人发现,这些提取物的组合以协同的方式起作用以提高和保持CBr2活性,这会减轻发痒皮肤或瘙痒皮肤的感觉。
在以下子章节中描述本发明的这些和其它非限制性方面。
A.活性成分
紫松果菊是原产于北美的开花植物。提取物可以由全株、根、花、茎、叶、花/叶/茎、或叶/根获得。这类提取物是可以从多种来源(参见例如《国际化妆品成分词典和手册》,第12版,2008(“CTFA”),第1卷,第918-19页,其通过引用并入)商购获得的。在具体的实施方案中,使用全株提取物(参见CTFA的第918页)。在一些实施方案中,提取物是水提取物。本发明人发现这类提取物可以与人皮肤中的CBR2受体结合。
关于水飞蓟(Silybummarianum),其是一种原产于南欧和亚洲的植物。已知其生长红色到紫色的花、具有白色脉络的闪亮的淡绿色的叶子、和果实。本发明的水飞蓟提取物可以是水醇(水和变性乙醇)提取物,其包含水飞蓟素作为活性成分(水飞蓟素是包含水飞蓟宾(silibine)、水飞蓟丁(silicristine)、水飞蓟宁(silidianin)、异水飞蓟宾(isosolibine)和异水飞蓟丁(isosilicristine)的二氢黄酮醇衍生物的混合物)。水飞蓟的果实部分包含水飞蓟素。水飞蓟提取物可以通过浸软果肉,然后使果肉经过水和SD醇39-C(变性乙醇)的水醇溶液处理获取提取物来从该植物的果实部分获得。然后提取物进行过滤,并包装用于存储,或被添加到本发明的组合物中。除了这种提取方法外,水飞蓟提取物可以从ProvitalS.A(西班牙)以商品名PRONALENSILYMARINHSC或PRONALENSILYMARINSPE购买。在一些实施方案中,提取物是水提取物。该提取物可以用于处理例如由干燥皮肤造成的皮肤中的炎性反应。
对于甘油,其是一种具有以下化学结构的多元醇:
其同样是可以从多种来源(参见例如《国际化妆品成分词典和手册》,第12版,2008(“CTFA”),第1卷,第1050-61页,其通过引用并入)商购获得的。甘油是已知的用于皮肤的保湿剂。
关于包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物,这种混合物是可以从Symrise(德国)以商品名获得的。产品是己基癸醇、红没药醇、硬脂酸、N-棕榈酰羟基脯氨酸鲸蜡酯和油菜(油菜籽)甾醇的组合。
另外,如上所述,本发明的组合物还可以包含迷迭香酸-α-D-葡糖苷。该化合物是迷迭香酸和葡萄糖之间形成的酯。其具有以下化学结构:
其是可以从LibraGen(图卢兹,法国)以商品名RosmarinylTMGlucoside商购获得的。该成分可以用于处理例如由干燥皮肤造成的皮肤中的炎性反应。
除了可以商购获得上文确定的提取物之外,所述提取物还可以通过获得相应的植物或其部分以通过本领域普通技术人员已知的提取物方法制备提取物来制备。例如,本领域普通技术人员通过本领域已知的任意合适的方法能够从相应植物的全株或部分分离上文确定的提取物中的任意一种。在一个非限制性实例中,可以通过机械手段使植物(或植物的任意部分)破裂,从而产生泥状物。然后加工该泥状物使其基本上不含杂质或不期望的固体。然后将所述泥状物倒入浅的器皿中,并快速暴露于低温,即速冻,例如在-20℃下或更低的温度下,优选在真空条件下进行以除去水含量(冻干)。然后,得到的提取物可以用在本发明的组合物中。
在其它方面,可以对其全株或其任意部分使用基于水、醇、水-醇或油的提取技术或其组合来制备提取物。在该过程中,将期望的植物部分或整个植物粉碎(例如搅拌机),然后使其经受期望的溶剂(例如水、醇、水/醇或基于油的溶剂)以获得期望的提取物。然后提取物可以以液体形式储存、冻干、或经受进一步的加工技术(例如加热、冷却等)。提取方法对提取领域的普通技术人员来说说众所周知的(例如浸渍、浸泡、渗滤、蒸煮、煎煮、热连续提取、水-醇提取、逆流提取、微博辅助提取、超声提取、超临界流体提取、植物提取(例如用氢氟碳溶剂)等)。
B.本发明的组合物
预期本发明的组合物可以包含本说明书全文所描述的任意活性物或其任意组合。在特定的方面,活性物可以进行组合(例如紫松果菊提取物、水飞蓟提取物、甘油以及包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物)。组合物可以包含任意数目的本说明书全文所描述的附加成分的组合。在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,组合物在其最终形式中可以包含、主要由以下组分组成或由以下组分组成: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%或其间可得到的任意范围的在本说明书的全文和权利要求所提及的成分中的至少一种。在非限制性方面,百分比可以按整个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,给定组合物中的浓度可以根据成分的添加、替换和/或去除而改变。
本发明公开的组合物还可以包含多种抗氧化剂以阻止一种或更多种组分的氧化。另外,可以通过防腐剂,例如多种抗细菌剂和抗真菌剂,包括但不限于对羟基苯甲酸酯(例如对羟基苯甲酸甲酯、对羟基苯甲酸丙酯)、氯丁醇、苯酚、山梨酸、硫汞撒或其组合来防止微生物的作用。在一些实施方案中,组合物不含对羟基苯甲酸酯。
C.载体
本发明的组合物可以并入到所有类型的载体中。合适载体的非限制性实例包括乳液(例如油包水、水包油包水、水包油、水包硅酮、硅酮包水、油包水包油、硅酮包水包油的乳液)、乳霜、润肤露、溶液(水的或者水-醇的)、无水基质(例如口红和粉末)、凝胶和软膏,或通过其它方法或本领域普通技术人员会知道的前述方法的任意组合(Remington's,1990)。变体和其它合适的载体对于熟练技术人员是明显的,并且适用于本发明。在特定的方面,重要的是,选择化合物、成分和试剂的浓度和组合,使得该组合是化学相容的并且不形成从最终产物中沉淀出来的络合物。
还预期在本说明书全文中确定的成分,包括但不限于紫松果菊提取物、水飞蓟提取物、甘油以及包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物、或其任意组合可以单独地或组合地进行包封以用于递送至目标区域,如皮肤。包封技术的非限制性实例包括使用脂质体、囊泡和/或纳米颗粒(例如生物可降解的和生物不可降解的胶体颗粒,其包含其中捕获、包封和/或吸附有所述成分的聚合材料——实例包括纳米球和纳米胶囊),所述脂质体、囊泡和/或纳米颗粒可以用作递送载体以将成分递送到皮肤(参见例如美国专利第6387398号;美国专利第6203802号;美国专利第5411744号;Kreuter1998)。
D.化妆品产品和制品
本发明的组合物还可以用在许多化妆品产品中,包括但不限于防晒产品、免晒皮肤美黑产品、毛发产品、手指甲产品、保湿霜、益肤霜和蜜露、柔软剂、日用乳液、凝胶、软膏、粉底、晚霜、口红、洗面乳、爽肤水、面膜或其它已知的化妆品产品或应用。另外,化妆品产品可以配制为保留型或洗去型产品。在特定的方面,本发明的组合物为独立的产品。
E.附加成分
除了紫松果菊提取物、水飞蓟提取物、甘油以及包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物、本说明书全文所公开的成分之外,本发明的组合物可以包含附加成分,如化妆品成分和药物活性成分。这些附加成分的非限制性实例在以下子章节中进行描述。
1.化妆品成分
CTFA国际化妆品成分词典和手册(InternationalCosmeticIngredientDictionaryandHandbook,2004和2008)描述了多种可以在本发明的环境下使用的非限制性化妆品成分。这些成分种类的实例包括:芳香剂(人造的和天然的)、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)、吸附剂、润滑剂、溶剂、保湿剂(包括例如润肤剂、湿润剂、成膜剂、闭塞剂和影响皮肤天然保湿机制的试剂)、拒水剂、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(例如类固醇和非类固醇类抗炎药)、植物提取物(例如芦荟、柑橘、黄瓜提取物、银杏、人参和迷迭香)、抗菌剂、抗氧化剂(例如BHT和生育酚)、螯合剂(例如乙二胺四乙酸二钠和乙二胺四乙酸四钠)、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(例如辛烯基琥珀酸淀粉铝、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酯)、湿润剂(例如山梨醇、脲和甘露醇)、剥离剂、防水剂(例如氢氧化钠镁/铝硬脂酸盐)、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、透明质酸和甘草酸二钾)。这些附加成分中一部分的非限制性实例在以下子章节中提供。
a.紫外吸收剂
可以与本发明的组合物组合使用的紫外吸收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、戊基二甲醇PABA酯和辛基二甲醇PABA酯)、PABA丁酯、PABA乙酯、乙基二羟基丙醇PABA酯、二苯甲酮(氧苯酮、磺异苯酮、二苯甲酮和二苯甲酮-1到12)、肉桂酸盐/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、甲氧基肉桂酸DEA盐、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、2-羟基-1,4-萘醌和二羟基丙酮、乙基己基三嗪酮、二辛基丁酰胺基三嗪酮、苯亚甲基丙二酸脂聚二甲基硅氧烷、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、亚甲基双苯并三唑基四甲基丁基苯酚和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.保湿剂
可以与本发明的组合物一起使用的保湿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、天然保湿因子、PEG-15丁二醇、聚甘油山梨醇、吡咯烷酮羧酸的盐、PCA钾、丙二醇、葡糖醛酸钠、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、翠叶芦荟提取物、翠叶芦荟凝胶、药蜀葵提取物、杏(prunusarmeniaca)仁油、精氨酸、精氨酸天冬氨酸盐/酯、山金车提取物、天冬氨酸、鳄梨(perseagratissima)油、屏障鞘脂、丁醇、蜂蜡、山萮醇、β-谷甾醇、白桦(betulaalba)树皮提取物、琉璃苣(Boragoofficinalis)提取物、假叶树(ruscusaculeatus)提取物、丁二醇、金盏花提取物、金盏花油、小烛树(euphorbiacerifera)蜡、菜籽油、辛酸/癸酸甘油三酯、豆蔻(elettariacardamomum)油、巴西棕榈(coperniciaerifera)蜡、胡萝卜(daucuscarotasativa)油、蓖麻(ricinuscommunis)油、神经酰胺、地蜡、十六/十八醇聚醚-5、十六/十八醇聚醚-12、十六/十八醇聚醚-20、鲸蜡硬脂醇辛酸酯、十六醇聚醚-20、十六醇聚醚-24、鲸蜡醇乙酸酯、鲸蜡醇辛酸酯、鲸蜡醇棕榈酸酯、洋甘菊(anthemisnobilis)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(theobromacacao)脂、椰油醇-辛酸酯/癸酸酯、椰子(cocosnucifera)油、胶原蛋白、胶原蛋白氨基酸、玉米(zeamays)油、脂肪酸、癸基油酸酯、聚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、乙氧基二乙二醇、亚油酸乙酯、蓝桉油、月见草(oenotherabiennis)油、脂肪酸、斑点老鹳草油、葡萄糖胺、葡糖谷氨酸酯、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、乙二醇硬脂酸酯、乙二醇硬脂酸酯SE、葡糖氨基葡聚糖、葡萄(vitisvinifera)籽油、美洲榛(corylusamericana)坚果油、欧洲榛(corylusavellana)坚果油、己二醇、透明质酸、杂交红花(carthamustinctorius)油、氢化蓖麻油、氢化椰油酸甘油酯、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、氢化牛脂酸甘油酯、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、羟基化羊毛脂、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(jasminumofficinale)油、霍霍巴(buxuschinensis)油、巨藻、石栗(aleuritesmoluccana)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(lavandulaangustifolia)油、卵磷脂、柠檬(citrusmedicalimonum)油、亚油酸、亚麻酸、澳洲坚果油、麦芽糖醇、母菊(chamomillarecutita)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(citrusaurantiumdulcis)油、棕榈(elaeisguineensis)油、棕榈酸、泛硫乙胺、泛醇、泛醇基乙基醚、石蜡、PCA、桃(prunuspersica)仁油、花生(arachishypogaea)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、十五内酯、薄荷(menthapiperita)油、凡士林、磷脂、多氨基酸多糖缩合物、聚甘油(3)二异硬脂酸酯、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(oryzasativa)糠油、RNA、迷迭香(rosmarinusofficinalis)油、玫瑰油、红花(carthamustinctorius)油、鼠尾草(salviaofficinalis)油、檀香(santalumalbum)油、丝氨酸、血清蛋白、芝麻(sesamumindicum)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、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(glycinesoja)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、向日葵(helianthusannuus)籽油、甜杏仁(prunusamygdalusdulcis)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(canangaodorata)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。在特定的方面,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个亚乙基氧单元的硬脂醇的聚乙二醇醚、具有平均约1到约5个亚乙基氧单元的鲸蜡醇的聚乙二醇醚及其混合物。
e.乳化剂
在本发明的特定方面,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的、阳离子的、阴离子的和两性离子的乳化剂(参见McCutcheon's,1986;美国专利第5011681号;4421769号;3755560号)。非限制性实例包括甘油酯、丙二醇酯、丙二醇的脂肪酸酯、聚丙二醇的脂肪酸酯、山梨醇的酯、失水山梨醇酐酯、羧酸共聚物、葡萄糖的酯和醚、乙氧基化的酯、乙氧基化的醇、磷酸烷基酯、聚乙二醇脂肪醚磷酸酯、脂肪酸酰胺、酰基乳酸酯、脂肪酸盐、TEA硬脂酸酯、DEA油醇聚醚-3磷酸酯、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、鲸蜡硬酯醇聚醚-20、PPG-2甲基葡萄糖醚二硬脂酸酯、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硬脂酸酯及其混合物。
f.含硅酮的化合物
在非限制性方面,含硅酮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意成员。通过改变-Si-O-链的长度、侧基和交联,硅酮可以合成为各种各样的材料。它们的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硅酮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。在特定的方面,含硅酮的化合物包括硅油,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、聚硅酮-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它们的混合物和其它任意给定比例的有机硅氧烷材料,以根据预期的应用(举例来说,对特定区域例如皮肤、毛发或眼睛)达到期望的稠度和应用特征。“挥发性硅油”包括具有低气化热的硅油,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);低黏度聚二甲基硅氧烷,即黏度大约为50cst或更低的聚二甲基硅氧烷(举例来说,聚二甲基硅氧烷,例如道康宁200-0.5cst流体)。DowCorningFluid可以从密歇根州米德兰的DowCorningCorporation购得。在CTFA化妆品成分词典的第三版中(通过引用并入),环聚二甲基硅氧烷和聚二甲基硅氧烷分别被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的线性硅氧烷混合物。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GeneralElectricCo.,SiliconeProductsDiv.和密歇根州艾德里安的SWSSiliconesDiv.ofStaufferChemicalCo.购得的那些。
g.精油
精油包括来自药草、花朵、树木和其它植物的油。这类油一般以植物细胞间微小的液滴存在,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、花香提取(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,但是随着时间其被氧化并且颜色变得更深。精油不溶于水,但溶于醇、醚、固定油(植物的)和其它有机溶剂。在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。
精油一般通过油被发现的来源植物命名。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、香柠檬油、玫瑰木油、香柏油、甘菊油、鼠尾草油、香紫苏油、丁香油、柏木油、桉油、茴香油、海茴香油、乳香油、香叶油、姜油、葡萄柚油、茉莉油、杜松子油、薰衣草油、柠檬油、柠檬草油、梨莓油、橘子油、甘牛至油、没药油、苦橙花油、橙油、绿叶油、胡椒油、黑胡椒油、苦橙叶油、松油、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、依兰依兰。还预期本领域技术人员已知的其它精油在本发明的环境下是有用的。
h.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的组合物的稳定性。在本发明的特定方面,增稠剂包括氢化聚异丁烯或三羟基硬脂酸甘油酯,或两者的混合物。
可以在本发明的环境下使用的另外的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一种或更多种衍生自丙烯酸的单体的交联化合物、取代的丙烯酸和这些丙烯酸和取代的丙烯酸的盐和酯,其中所述交联剂含有两个或更多个碳-碳双键,并衍生自多元醇(参见美国专利第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CarbopolTM900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。在美国专利第5100660号;4849484号;4835206号;4628078号;4599379号中描述了实例。
聚丙烯酰胺聚合物(包括非离子的聚丙烯酰胺聚合物,其包括取代支化的或未支化的聚合物)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、丙烯酰胺和经取代的丙烯酰胺与丙烯酸和经取代的丙烯酸的多嵌段共聚物。
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-C30直链或支链烷基基团通过醚键进行进一步改性。一般这些聚合物为C10-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,其包含每三个单元具有一个(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阿拉伯树胶、琼脂、藻胶、藻酸、藻酸铵、支化淀粉、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。
i.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))、尼泊金酯(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
还预期药物活性成分对本发明的组合物是有用的。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、肛门直肠的、抗组胺药、包括非甾族消炎药在内的消炎剂、抗生素、抗菌剂、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、烧伤处理剂、烧灼剂、脱色剂、脱毛剂、尿布疹处理剂、酶、毛发生长刺激剂、包括DFMO及其盐和类似物在内的毛发生长抑制剂、止血剂、角质分离剂、口疮处理剂、唇疱疹处理剂、牙科或牙周处理剂、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、晒伤处理剂、遮光剂、经皮活性物、鼻活性物、阴道活性物、疣处理剂、创伤处理剂、创伤愈合剂等。
F.试剂盒
还预期试剂盒用于本发明的特定方面。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、高压容器、防渗容器、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,其中保存分散体或组合物或期望的瓶子、分配器或包装。试剂盒和/或容器在其表面可包含标记。举例来说,标记可以是字词、短语、缩写、图片或符号。
所述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)以分配期望量的组合物。组合物可以分配为喷雾、气溶胶、液体、流体或半固体。容器可以具有喷雾、抽吸或挤压机构。试剂盒还可以包含使用试剂盒组分以及使用任意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解释。
实施例
列出以下实施例以说明本发明的特定非限制性方面。本领域技术人员应理解,以下实施例中所公开的技术代表本发明人发现的在本发明的实践中发挥良好作用的技术。然而,根据本公开,本领域技术人员应理解,在所公开的具体实施方案中可以做出许多改变,并仍然获得相同或相似的结果,而不脱离本发明的精神和范围。
实施例1
组合物的非限制性实例
发现紫松果菊提取物(Naturex(法国))在体内与2型人类大麻素受体(CBr2)结合。其还通过使用Trolox当量抗氧化能力(TEAC)显示出是抗氧化剂,通过脂肪氧合酶(LO)分析显示出是酶抑制剂。该数据表明该提取物可以抑制调节皮肤发痒的感觉神经纤维(数据未示出)。发现水飞蓟提取物(ProvitalS.A(西班牙))抑制脂肪酸酰胺水解酶(FAAH)活性。已知FAAH破坏大麻素,这进而可活化CBr2。还发现水飞蓟提取物抑制COX-1和COX-2(LO分析),抑制角质细胞炎性细胞因子,包括TNF-α、CGRP、IL-1、IL-6和IL-8,并且是抗氧化剂(ORAC测试、TEAC测试)。本发明人发现,这些提取物的组合以协同的方式起作用以提高和保持CBr2活性,这可减轻发痒皮肤或瘙痒皮肤的感觉。
甘油是已知的保湿剂。还已知由Symrise以商品名销售的包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物具有皮肤保湿性能。
本发明人认为,通过将上述成分中的每一种组合到单一组合物中,整体效果能用于处理皮肤瘙痒,同时也处理干燥皮肤、皲裂皮肤或片状皮肤。本领域普通技术人员也可以使用表1和2中的测试载体来确定该成分的组合对发痒的皮肤或者干燥皮肤、皲裂皮肤或片状皮肤的效果。
表1*
成分 | %浓度(以重量计) |
相A | |
水 | 补足到100 |
黄原胶 | 0.1 |
M-对羟基苯甲酸酯 | 0.15 |
P-对羟基苯甲酸酯 | 0.1 |
柠檬酸 | 0.01 |
相B | |
鲸蜡醇 | 4.0 |
硬脂酸甘油酯+PEG 100 | 4.0 |
棕榈酸辛酯 | 4.0 |
聚二甲基硅氧烷 | 1.0 |
乙酸生育酚酯 | 0.2 |
相C | |
有效成分** | 5.0 |
*将黄原胶撒入水中并混合10分钟。然后,添加相A中的所有成分并加热到70至75℃。添加相B中的所有成分到单独的烧杯中并加热到70至75℃。在70至75℃下混合相A和B。继续搅拌并使组合物冷却到30℃。然后,边搅拌边添加相C的成分。
**可以使用本说明书中所描述的任意活性成分(或其组合)。例如,活性成分可以包括紫松果菊提取物、水飞蓟提取物、甘油以及包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。在其他方面,组合可以是紫松果菊提取物、水飞蓟提取物以及N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇。虽然表1制剂中活性成分的总量为5%(w/w),但是预期可以增加或减少活性成分的量以获得预期的结果,其中水量可以相应地增加/减少(例如足量)。
表2*
成分 | %浓度(以重量计) |
相A | |
水 | 补足到100 |
M-对羟基苯甲酸酯 | 0.2 |
P-对羟基苯甲酸酯 | 0.1 |
Na2EDTA | 0.1 |
牛油果脂 | 4.5 |
凡士林 | 4.5 |
甘油 | 4.0 |
丙二醇 | 2.0 |
Finsolve TN | 2.0 |
相B | |
Sepigel 305 | 2.0 |
相C | |
有效成分** | 2.0 |
*将相A中的成分添加到烧杯中并边搅拌边加热到70至75℃。然后,将相B的成分与相A添加到一起并随着搅拌冷却到30℃。然后,边搅拌边添加相C的成分。
**可以使用本说明书中所描述的任意活性成分(或其组合)。例如,活性成分可以包括紫松果菊提取物、水飞蓟提取物、迷迭香酸-α-葡糖苷、甘油以及包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。在其他方面,组合可以是紫松果菊提取物、水飞蓟提取物以及N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇。虽然表2制剂中活性成分的总量为2%(w/w),但是预期可以增加或减少活性成分的量以获得预期的结果,其中水量可以相应地增加/减少(例如足量)。
实施例2
体内数据
使用包含0.50重量%的紫松果菊提取物、1.0重量%的水飞蓟提取物、2.0重量%的包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物和15.0重量%的甘油的组合物进行体内测试。紫松果菊提取物由Naturex(法国)以商品名ECHINACEAPURPUREAHERBPE购得,水飞蓟提取物由ProvitalS.A(西班牙)以商品名PRONALENSILYMARIN购得,包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物由Symrise(德国)以商品名购得。具体地,使用专用的不含防腐剂的基底润肤露制剂(“VinnyBase”)进行干燥度、纹理和发痒的2周临床评价,紫松果菊提取物、水飞蓟提取物、甘油和包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物并入到所述制剂中。未处理的腿用作对照。
研究设计和方法:招募年龄在18至69岁并且是白种人的二十二(22)位女性小组成员来完成研究。小组成员阅读并签署了知情同意。该研究要求在2周的周期内4次访视测试机构。访视如下:第0天(基线)、第2天、第7天和第14天。每次测量之前,使小组成员与测试环境平衡15分钟。该研究需要在基线访视之前的一周洗净期,指示小组成员用IvoryTM皂条每天清洗小腿至少两次,用温水漂洗。指示小组成员根据处理随机化代码将产品施用到一条腿的下侧面。未处理的腿用作对照。表1至4中提供研究的结果。
目视评级:在所有访视中,由专家评级员使用VisualAnalogueScale(VAS)(轻度=1至3.9,中等=4至6.9,重度=7至10)和顺序量表(0=无干燥迹象至4=重度成片、剥落和/或开裂)对小组成员的下侧面腿的皮肤纹理和皮肤干燥度进行目视评级。
主观的痒问卷调查:仅在基线处和第14天(最终)访视时要求全部小组成员完成主观的痒问卷调查,以基于0(无)至10(重度)的VAS标尺来评定她们感觉的皮肤发痒的强度。
水分蒸发测试(Vapometer)仪测量:评级之后通过使用水分蒸发测试仪进行经表皮水损耗(TEWL)的测量。
产品施用:指示小组成员每天两次将产品施用至一条腿的下侧面区域,持续2周。要求小组成员在基线访视之前避免她们腿部的长期日照和任意保湿剂、剃毛膏和止痒产品的使用,直到研究结束。还要求她们在所有访视之前的四十八小时内停止对小腿进行剃毛。要求她们在每次访视之前约1小时用IvoryTM皂条清洗小腿。
统计分析:使用配对t检验将在第2天、第7天和第14天获得的视觉评分分数变化和水分蒸发测试仪数据与基线进行比较。认为统计显著性在p值≤0.05。
表3:关于处理组和对照组的专家评级和主观的痒问卷调查
*在95%的置信水平与基线相比统计显著,^与基线相比明显更差,NI:无改善,NS:在95%的置信水平不显著,NA:不适用
表4:处理组和对照组之间的平均目视评级和主观的痒问卷调查评分
¥在95%的置信水平统计显著,NA:不适用
表5:与基线相比的处理组和对照组的TWEL分析
^在95%的置信水平与基线相比明显更差;NS:在95%的置信水平不显著,NI:无改善
表6:处理组和对照组的平均TEWL读数
在95%的置信水平统计显著
乳霜与基线和未处理组相比在第2、7和14天明显改善皮肤干燥度和皮肤纹理。未处理组与基线相比在2周后没有显示出任意皮肤干燥度和纹理的改善。基于自身评估的痒问卷调查,与基线相比,在处理组中痒强度第14天访视时显示统计显著的改善。然而,对于未处理组在2周后没有痒强度的明显变化。与基线相比,在处理组中止痒乳霜在2周内没有明显改善皮肤屏障。然而,与未处理组相比,止痒乳霜在第7天和第14天在保持皮肤屏障方面明显更好。与基线相比,在第2周未处理组中皮肤屏障明显恶化。
实施例3
分析
除了上述分析之外,本说明书和权利要求全文所公开的成分的组合的功效可以通过使用以下分析来确定。
红斑分析:测量皮肤发红减少的分析可以使用MinoltaChromometer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来引发。该区域用封闭的贴片保护24小时。24小时后,除去贴片,可以使用MinoltaChromaMeter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。测定之后,立即用本发明的组合物处理该区域。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/水合的益处可以通过利用以NovaDermalPhaseMeter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能。当皮肤干燥时,其导电很差。当其变得更加含水时,产生增加的导电性。因此,皮肤阻抗(与导电性有关)的变化可以用于评价皮肤水合的变化。装置可以根据仪器说明针对每个测试日进行校准。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: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。在脸的每一侧进行三个独立的阻抗测定,并对其进行记录和平均。阻抗计可以使用T5设定,其对施用到脸上每五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。
皮肤清透度和雀斑与老年斑减少的分析:皮肤清透度和雀斑与老年斑减少使用MinoltaChromometer进行评价。肤色改变可以使用MinoltaChromaMeter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*值测量肤色在红色区域的变化。这用来确定组合物是否导致刺激。测量可以在脸的每一侧进行并进行平均,作为左边和右边脸的值。皮肤清透度也可以使用MinoltaMeter进行测量。测量是MinoltaMeter的a*、b、和L值的组合,并与皮肤的亮度有关,而且非常好的对应皮肤的光滑度和水合。皮肤测定如上进行。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五点标准Kligmanscale进行确定:(0)皮肤是柔软和湿润的;(1)皮肤呈现正常而没有可见的干燥;(2)皮肤触摸感觉轻微干燥而没有可见的剥落;(3)皮肤感觉干燥、坚韧并且具有有些鳞屑的发白的外观;以及(4)皮肤感觉非常干燥、粗糙并且具有有鳞屑的发白的外观。评价可以由两个临床医师独立进行并进行平均。
肤色临床评分分析:肤色的临床评分可以通过十点模拟数值刻度实施:(10)平滑的均匀的皮肤、粉红棕色的颜色。手持放大镜检查时没有暗的、发红的或有鳞的斑块。皮肤的微观纹理摸上去非常均匀;(7)不用放大镜观察均匀的肤色。没有鳞状区域,但是有由于色素淀积或红斑引起的疹斑。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的纹理。少量鳞片。一些区域摸上去粗糙的皮肤;以及(1)不均匀的皮肤着色和纹理。多个区域的鳞片和疹斑,色素减退型、发红的或黑色的斑点。大面积的直径超过1cm的不均匀着色。评价由两个临床医师独立进行并进行平均。
皮肤平滑度的临床评分分析:皮肤光滑度的临床评分可以通过一个十点模拟数值刻度进行分析:(10)光滑的,皮肤是湿润的和闪光的,手指划过表面时没有阻力;(7)一定程度光滑的,微小的阻力;(4)粗糙的、可见地改变的,摩擦时有摩擦力;以及(1)粗糙的、片状的、不均匀的表面。评价由两个临床医师独立进行并进行平均。
用Packman等人(1978)公开的方法进行的皮肤光滑度和皱纹减少的分析:皮肤光滑度和周围的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,每一受试者就诊时,对每一受试者的表面面线(SFL)的深度、浅度和总数量都可以进行认真的评分和记录。通过将数量因子乘以深度/宽度/长度因子得到数字的分数。获得眼睛区域和嘴巴区域(左侧和右侧)的分数,加到一起作为总的皱纹分数。
用HargensBallistometer进行的皮肤紧致度分析:皮肤紧致度可以用HargensBallistometer,一种通过在皮肤上落下一个小物体并记录前两个反弹峰来评价皮肤弹性和紧致度的装置,进行测量。ballistometry是使用相对钝的探头(4平方毫米-接触面积)的小的轻量探测器。探测器轻轻地穿透进入皮肤,导致依赖于皮肤外层性质的测量,所述皮肤外层包括角质层和外表皮以及部分真皮层。
用GasBearingElectrodynamometer进行的皮肤柔软度/柔韧性分析:皮肤柔软度/柔韧性可以使用GasBearingElectrodynamometer,一种测量皮肤应力/应变性能的仪器,进行评价。皮肤的黏弹性与皮肤保湿有关。可以通过用双面胶将探测器附着在皮肤表面实现对脸颊区域特定位点的测量。大约3.5gm的力平行施加于皮肤表面,精确地测量皮肤的位移。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)。
用复制品进行的线条和皱纹的显现分析:皮肤上线条和皱纹的显现可以使用复制品进行评价,所述复制品是皮肤表面的印模。可以使用如硅橡胶的材料。复制品可以通过图像分析进行分析。线条和皱纹可见性的变化可以通过利用硅复制品形成受试者的脸并用计算机图像分析系统分析复制品图像进行客观地定量。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线条覆盖的区域。
用表面光度仪/记录针的方法进行的皮肤表面轮廓分析:皮肤表面轮廓可以通过使用表面光度仪/记录针的方法进行测量。这包括闪光或拖动记录针穿过复制品表面。记录针的垂直位移通过距离传感器可以录入计算机,在扫描复制品的一定距离后,皮肤轮廓的分析可以以二维曲面产生。该扫描可以沿着固定的轴重复任意次数以产生模拟的皮肤3-D图像。使用记录针技术可以获得十个随机的复制品截面,并组合产生平均值。感兴趣的值包括Ra,其为通过积分相对于平局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,以及Rz,其为平均峰振幅减去平均峰高度。数值以用mm为单位标定的数值给出。设备应在每次使用前通过扫描已知数值的金属标准物进行标准化。Ra值可以通过下式计算:Ra=标准化粗糙度;lm=横向(扫描)长度;以及y=轮廓位置相对于平均轮廓高度的绝对值(x-轴)。
MELANODERMTM分析:在其他非限制性方面,本发明的组合物的功效可以通过使用皮肤类似物,例如举例来说MELANODERMTM,进行评估。黑素细胞,皮肤类似物中细胞的一种,当暴露于L-二羟苯基丙氨酸(L-DOPA)(黑色素的前体)时阳性着色。皮肤类似物MELANODERMTM可以用各种含有本发明的组合物和增白剂的赋形剂进行处理,或仅使用赋形剂作为对照物。或者,未处理的皮肤类似物样品可以用作对照物。
ORAC分析:芳香的皮肤活性成分和组合物的氧自由基吸收(或吸收率)能力(ORAC)还可以通过测量这类成分或组合物的抗氧化活性进行分析。该分析可以定量抑制氧化剂,例如已知导致损害细胞(例如皮肤细胞)的氧自由基,的活动的程度及所用时间。芳香的皮肤活性成分和组合物的ORAC值可以通过本领域普通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;Cao等人(1993),其全部内容通过引用并入)。总之,Cao等人(1993)描述的分析测量了抗氧化化合物在测试材料中抑制过氧自由基生成物AAPH引起的B-藻红蛋白(B-PE)荧光下降的能力。
基质金属蛋白酶活性(MMP3;MMP9)分析:体外的基质金属蛋白酶(MMP)抑制分析。MMP是胞外蛋白酶,其凭借宽的底物特异性在许多正常的和疾病状态起作用。MMP3底物包括胶原蛋白、纤维粘连蛋白和层粘连蛋白;而MMP9底物包括胶原蛋白VII、纤维粘连蛋白和层粘连蛋白。使用来自BioMolInternational的用于MMP3(AK-400)和MMP-9(AK-410)的比色药物发现试剂盒,该分析设计用于测量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裂解位点的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处的吸光度进行检测(在pH6.0和高于7时,ε=13600M-1cm-1)。
B16色素沉着分析:黑素生成是黑素细胞产生黑色素的过程,黑色素是一种天然产生的给予皮肤、毛发和眼睛颜色的色素。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黑素细胞(ATCC),一种永生化的小鼠黑色素瘤细胞系,来分析化合物对黑素生产的效果。该分析的终点是黑色素产生和细胞活性的分光光度测量。B16-F1黑色素细胞可以在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,然后用本说明书所公开的活性成分、成分的组合或具有所述组合的组合物中的任意一种处理6天。培育之后,黑色素分泌通过在405nm处的吸收进行测量,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一种细胞外基质蛋白。增加的胶原蛋白合成帮助改善皮肤坚实度和弹性。该生物分析可以用于通过人类表皮成纤维细胞来检查本说明书所公开的活性成分、成分的组合或具有所述组合的组合物中的任意一种对原胶原蛋白肽(胶原蛋白的前体)的生成的影响。该分析的终点是反映原胶原蛋白肽的存在和细胞活性的分光光度测量。该分析采用定量的三明治酶免疫分析技术,因此对原胶原蛋白肽特异的单克隆抗体预先涂覆在微孔板上。标准品和样品可以移液到孔中,存在的所有原胶原蛋白肽由固定化的抗体结合。冲走所有未结合的物质后,可以将对原胶原蛋白肽特异的酶联多克隆抗体添加到孔中。冲洗以去除所有未结合的抗体-酶试剂之后,可以将底物溶液添加到孔中,颜色显现与最初步骤中结合的原胶原蛋白肽的量成比例,使用微孔板测定仪在450nm处检测。可以停止颜色显现,并可以测量颜色的强度。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次融合的正常人类成熟表皮成纤维细胞(CascadeBiologics)可以用本说明书所公开的活性成分、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。培养之后,可以收集细胞培养基,并可以使用来自Takara(#MK101)的三明治酶联免疫吸附分析(ELISA)定量原胶原蛋白肽的分泌量。
肿瘤坏死因子-α(TNF-α)分析:TNF超家族的原型配体,TNF-α,是一种在炎症中起主要作用的多效细胞因子。其表达的增加与促炎活性上调有关。该生物分析可以用于通过人类表皮角质细胞来分析本说明书所公开的活性成分、成分的组合或具有所述组合的组合物中的任意一种对TNF-α的生成的影响。该分析的终点可以是反映TNF-α的存在和细胞活性的分光光度测量。该分析采用定量的三明治酶免疫分析技术,因此对TNF-α特异的单克隆抗体预先涂覆在微孔板上。标准品和样品可以移液到孔中,存在的所有TNF-α由固定化的抗体结合。冲走所有未结合的物质后,可以将对TNF-α特异的酶联多克隆抗体添加到孔中。冲洗以去除所有未结合的抗体-酶试剂之后,可以将底物溶液添加到孔中,颜色显现与最初步骤中结合的TNF-α的量成比例,使用微孔板测定仪在450nm处检测。可以停止颜色显现,并可以测量颜色的强度。在37℃下5%的CO2中在EpiLife标准生长培养基(CascadeBiologics)中培养的亚融合的正常人类成熟角质细胞(CascadeBiologics)可以用佛波醇-12-豆蔻酸酯-13-乙酸酯(PMA,10ng/ml,SigmaChemical,#P1585-1MG)和本说明书中所公开的活性成分中的任一种、成分的组合或具有所述组合的组合物处理6小时。PMA已经显示导致TNF-α分泌明显的增加,所述TNF-α分泌在处理6小时后达到峰值。培育之后,可以收集细胞培养基,并使用来自R&DSystems(#DTA00C)的三明治酶联免疫吸附分析(ELISA)定量TNF-α的分泌量。
抗氧化(AO)分析:测量本说明书中所公开的活性成分中的任一种、成分的组合或具有所述组合的组合物的总的抗氧化能力的体外生物分析。所述分析依赖样品中抗氧化剂抑制(2,2'-联氮-双-[3-乙基苯并噻唑啉磺酸盐])被正铁肌红蛋白氧化成的能力。活生物体的抗氧化系统包含酶,例如超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶;高分子,例如白蛋白、血浆铜蓝蛋白和铁蛋白;和大量小分子,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。內源的源自食物的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的任意单个化合物更强的对抗反应性氧或氮自由基侵袭的保护。因此,总的抗氧化能力与测量单独组分获得的相比可以给出更相关的生物信息,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,一种水溶性生育酚类似物的进行比较,并以Trolox的摩尔当量进行定量。来自CaymanChemical(AnnArbor,美国密歇根州)的抗氧化能力试剂盒#709001可以用作体外生物分析来测量本说明书中所公开的活性成分的任一种、成分的组合或具有所述组合的组合物中每一种的总的抗氧化能力。方案可以根据制造商的建议进行。所述分析依赖样品中的抗氧化剂抑制(2,2'-联氮-双-[3-乙基苯并噻唑啉磺酸盐])被正铁肌红蛋白氧化成。可以将样品中抗氧化剂预防ABTS氧化的能力与Trolox、即一种水溶性生育酚类似物的进行比较,并以Trolox的摩尔当量进行定量。
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)的黑色素生物合成中催化两个步骤。酪氨酸酶位于黑素细胞中,并产生给予皮肤、毛发和眼睛颜色的黑色素(芳香醌化合物)。纯化的蘑菇酪氨酸(Sigma)可以在存在或不存在本说明书中所公开的活性成分的每一种、成分的任一种组合或具有所述组合的组合物的条件下利用其底物L-Dopa(Fisher)来培养。色素形成可以通过在490nm测定的比色板进行评价。蘑菇酪氨酸酶活性的抑制百分比可以通过与未处理的对照物比较进行计算,以确定测试成分或其组合抑制纯化酶活性的能力。测试提取物的抑制与曲酸(Sigma)的进行比较。
环氧合酶(COX)分析:体外环氧合酶-1和-2(COX-1、-2)抑制分析。COX是一种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换为过氧化氢内过氧化物(前列腺素G2;PGG2),过氧化物酶组分将内过氧化物(前列腺素H2;PGH2)还原为相应的醇,前列腺素、凝血噁烷和环前列腺素的前体。该COX抑制筛选分析测量环氧合酶的过氧化物酶组分。过氧化物酶活性通过监测氧化的N,N,N',N'-四甲基-对苯二胺(TMPD)的出现比色地进行分析。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。比色的COX(绵羊)抑制剂筛选分析(#760111,CaymanChemical)可以用于分析本说明书中所公开的活性成分中的每一种、成分的任一种组合或具有所述组合的组合物对纯化的环氧合酶(COX-1或COX-2)活性的影响。根据制造商的说明,纯净的酶、血红素和测试提取物可以在分析缓冲液中混合,并在室温下摇动培育15分钟。培育之后,可以加入花生四烯酸和比色底物开始反应。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活性的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纯净酶活性的能力。
脂肪氧合酶(LO)分析:体外的脂肪氧合酶抑制分析。LO是非血红素的含铁的加双氧酶,其催化分子氧加成到脂肪酸。亚油酸盐/酯和花生四烯酸盐/酯是植物中和动物中LO的主要底物。然后,花生四烯酸可以转换为羟基二十三烯(HETE)酸衍生物,其随后转换为白三烯,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-、12-或15-LO)产生的氢过氧化物提供一种精确的和方便的用于筛选脂肪氧合酶抑制剂的方法。比色的LO抑制剂筛选试剂盒(#760700,CaymanChemical)可以用于确定本说明书中所公开的活性成分中的每一种、成分的任一种组合或具有所述组合的组合物抑制酶活性的能力。纯化的15-脂肪氧合酶和测试成分可以在分析缓冲液中混合,并在室温下摇动培育10分钟。培育之后,可以加入花生四烯酸开始反应,混合物在室温下再培育额外的10分钟。可以加入比色底物终止催化,颜色变化通过在490nm测定的荧光板进行评价。可以与未处理的对照相比来计算脂肪氧合酶活性的抑制百分比以确定本说明书中所公开的活性成分中的每一种、成分的任一种组合或具有所述组合的组合物抑制纯化酶的活性的能力。
弹性蛋白酶分析:来自MolecularProbes(美国俄勒冈州尤金)的弹性蛋白酶分析(试剂盒#E-12056)可以用作用于测量本说明书中所公开的活性成分中的每一种、成分的任一种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试剂盒含有可溶的牛颈韧带弹性蛋白,其可以用染料标记以使共轭荧光可以淬灭。非荧光的底物可以被弹性蛋白酶或其他蛋白酶消化以产生高荧光的片段。产生的荧光增强可以用荧光微孔板测定仪进行监测。来自弹性蛋白底物的消化产物在约505nm处具有吸收最大值,在约515nm处具有荧光发射最大值。当使用EnzChek弹性蛋白酶分析试剂盒用于弹性蛋白酶抑制剂的筛选时,肽、氯甲基酮可以用作选择性的、共同的弹性蛋白酶抑制剂。
油控制分析:用于测量皮脂腺中皮脂分泌的减少和/或皮脂腺中皮脂产生的减少的分析可以通过使用本领域普通技术人员已知的标准技术进行分析。在具体的例子中,可以使用前额。本说明书中所公开的活性成分中的每一种、成分的任一种组合或具有所述组合的组合物可以每天一次或两次地施用到前额的一部分一段固定的日子(例如1、2、3、4、5、6、7、8、9、10、11、12、13、14或更多天),而前额的其他部分不用该组合物处理。在一段固定的日子期满后,皮脂分泌可以通过将细吸墨纸施用到处理过的和未处理的前额皮肤上进行分析。这是通过首先用湿的和干的布从处理过的和未处理的区域去除所有皮脂完成的。然后吸墨纸施用到处理过的和未处理的前额区域,可以绕着前额放置橡皮筋以轻轻地将吸墨纸压到皮肤上。2小时后,吸墨纸可以移去,使其干燥,然后进行透照。越深的吸墨纸对应于越多的皮脂分泌(或较浅的吸墨纸对应于减少的皮脂分泌。
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本说明书中所公开和要求保护的所有皮肤活性成分、组合物或方法根据本公开不需要不合适的实验即可制成和实现。尽管本发明的皮肤活性成分、组合物或方法按照具体的实施方案进行了描述,但是对于本领域技术人员明显的是,可以对所述皮肤活性成分、组合物或方法以及在本文所描述方法的步骤或步骤的顺序中实施变化,而不脱离本发明的概念、精神和范围。
参考文献
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Claims (33)
1.一种用于处理瘙痒的方法,其包括对有此需要的皮肤局部施用组合物,所述组合物包含有效量的紫松果菊提取物、水飞蓟提取物、甘油和包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物,其中所述组合物的局部施用处理瘙痒。
2.根据权利要求1所述的方法,其中所述组合物活化皮肤中的2型人类大麻素受体并抑制皮肤中的脂肪酸酰胺水解酶活性。
3.根据权利要求1至2中任一项所述的方法,其中所述紫松果菊提取物是水提取物。
4.根据权利要求1至3中任一项所述的方法,其中所述紫松果菊提取物来自全株。
5.根据权利要求1至4中任一项所述的方法,其中所述水飞蓟提取物是水提取物。
6.根据权利要求1至5中任一项所述的方法,其中所述水飞蓟提取物来自果实。
7.根据权利要求1至6中任一项所述的方法,其中所述组合物配制为乳霜、润肤露、乳液、精华或洗面乳。
8.根据权利要求1至7中任一项所述的方法,其中所述组合物是水包油乳液或油包水乳液。
9.根据权利要求1至8中任一项所述的方法,其中有效量是0.001重量%至10重量%的紫松果菊提取物、0.001重量%至10重量%的水飞蓟提取物和0.001重量%至10重量%的包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。
10.根据权利要求9所述的方法,其中有效量是0.50重量%的紫松果菊提取物、1.0重量%的水飞蓟提取物和2.0重量%的包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。
11.根据权利要求10所述的方法,其中有效量是15重量%的甘油。
12.根据权利要求1至9中任一项所述的方法,其中所述皮肤是瘙痒皮肤、干燥皮肤或红斑皮肤。
13.根据权利要求1至12中任一项所述的方法,其中将所述组合物施用至皮肤,并且在局部施用后在皮肤上保留至少5分钟。
14.根据权利要求1至13中任一项所述的方法,其中需要处理的皮肤是面部皮肤、腿部皮肤、踝部皮肤、臂部皮肤、手部皮肤或头皮皮肤。
15.根据权利要求1至14中任一项所述的方法,其中所述组合物还包含保湿剂、紫外吸收剂、抗氧化剂、结构化剂、乳化剂、含硅酮的化合物、精油、增稠剂和防腐剂中的至少一种。
16.根据权利要求1至15中任一项所述的方法,其中所述组合物还包含药物成分。
17.一种用于减轻与瘙痒相关的症状的方法,其包括对有此需要的皮肤局部施用组合物,所述组合物包含有效量的紫松果菊提取物、水飞蓟提取物和包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物,其中所述组合物的局部施用减轻与瘙痒相关的症状。
18.一种处理瘙痒的方法,其包括对瘙痒皮肤局部施用包含以下组分的组合物:
(a)紫松果菊提取物和水飞蓟提取物,其中所述提取物的组合活化所述瘙痒皮肤中的2型人类大麻素受体并抑制所述瘙痒皮肤中的脂肪酸酰胺水解酶活性;和
(b)甘油和包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物,其中甘油和包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物的组合使所述瘙痒皮肤湿润。
19.一种局部护肤组合物,所述组合物包含皮肤病学上可接受的载体、和以下成分的组合:紫松果菊提取物、水飞蓟提取物、甘油和包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。
20.根据权利要求19所述的局部护肤组合物,其中所述紫松果菊提取物是水提取物。
21.根据权利要求19至20中任一项所述的局部护肤组合物,其中所述紫松果菊提取物来自全株。
22.根据权利要求19至21中任一项所述的局部护肤组合物,其中所述水飞蓟提取物是水提取物。
23.根据权利要求19至22中任一项所述的局部护肤组合物,其中所述水飞蓟提取物来自果实。
24.根据权利要求19至23中任一项所述的局部护肤组合物,其中所述组合物还包含保湿剂、紫外吸收剂、抗氧化剂、结构化剂、乳化剂、含硅酮的化合物、精油、增稠剂和防腐剂中的至少一种。
25.根据权利要求19至24中任一项所述的局部护肤组合物,其中所述组合物还包含药物成分。
26.根据权利要求19至25中任一项所述的局部护肤组合物,其中所述组合物配制为乳霜、润肤露、凝胶或精华。
27.根据权利要求19至26中任一项所述的局部护肤组合物,其中所述组合物是水包油乳液或油包水乳液。
28.根据权利要求19至27中任一项所述的局部护肤组合物,其中所述组合物包含0.001重量%至10重量%的每种成分或成分的组合。
29.根据权利要求28所述的方法,其中有效量是0.50重量%的紫松果菊提取物、1.0重量%的水飞蓟提取物和2.0重量%的包含N-棕榈酰羟基脯氨酸鲸蜡酯/硬脂酸/油菜(油菜籽)甾醇的混合物。
30.根据权利要求29所述的方法,其中有效量是15重量%的甘油。
31.根据权利要求19至28中任一项所述的局部护肤组合物,其中所述组合物活化皮肤中的2型人类大麻素受体。
32.根据权利要求19至31中任一项所述的局部护肤组合物,其中所述组合物抑制皮肤中的脂肪酸酰胺水解酶活性。
33.根据权利要求19至28中任一项所述的局部护肤组合物,其中所述组合物活化皮肤中的2型人类大麻素受体并且抑制皮肤中的脂肪酸酰胺水解酶活性。
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CN105853289A (zh) * | 2016-05-05 | 2016-08-17 | 广州丹奇日用化工厂有限公司 | 含有石斛提取物的化妆品组合物及其应用 |
CN106265264A (zh) * | 2016-08-26 | 2017-01-04 | 珀莱雅化妆品股份有限公司 | 一种祛痘组合物及其制备方法 |
CN108578324A (zh) * | 2018-07-02 | 2018-09-28 | 上海新高姿化妆品有限公司 | 一种具有长效保湿功效的润肤霜及其制备方法 |
CN109674672A (zh) * | 2019-01-23 | 2019-04-26 | 广州葆妍生物科技有限公司 | 一种头皮护理组合物及其应用 |
CN113474000A (zh) * | 2019-01-29 | 2021-10-01 | Isp投资有限公司 | 获得广藿香叶提取物的方法及其化妆品用途 |
CN110101650A (zh) * | 2019-06-20 | 2019-08-09 | 李祥 | 一种消炎祛痘化妆品组合物 |
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KR20220125370A (ko) | 2022-09-14 |
US10111919B2 (en) | 2018-10-30 |
KR102440040B1 (ko) | 2022-09-02 |
US20160220623A1 (en) | 2016-08-04 |
EP2968108A1 (en) | 2016-01-20 |
US10842837B2 (en) | 2020-11-24 |
EP2968108A4 (en) | 2016-11-02 |
US20230321169A1 (en) | 2023-10-12 |
KR20150127282A (ko) | 2015-11-16 |
US20210030826A1 (en) | 2021-02-04 |
WO2014159238A1 (en) | 2014-10-02 |
KR102190710B1 (ko) | 2020-12-14 |
EP2968108B1 (en) | 2020-01-22 |
CN105188662B (zh) | 2018-07-06 |
US11547733B2 (en) | 2023-01-10 |
KR20200138834A (ko) | 2020-12-10 |
CA2904948A1 (en) | 2014-10-02 |
US9333230B2 (en) | 2016-05-10 |
US20190038692A1 (en) | 2019-02-07 |
US20140271525A1 (en) | 2014-09-18 |
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