CN116847871A - 护肤组合物及其使用方法 - Google Patents
护肤组合物及其使用方法 Download PDFInfo
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- CN116847871A CN116847871A CN202280012977.8A CN202280012977A CN116847871A CN 116847871 A CN116847871 A CN 116847871A CN 202280012977 A CN202280012977 A CN 202280012977A CN 116847871 A CN116847871 A CN 116847871A
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Abstract
本公开涉及分子量为约55kDa的重组胶原片段,以及包含所述重组胶原片段的组合物。还提供了产生所述重组胶原片段的方法和使用所述重组胶原片段进行治疗的方法。
Description
以电子方式递交的序列表(名称:4431_061PC01_Seqlisting_ST25.txt;大小:10,959字节;及创建日期:2022年2月4日)全文以引用方式并入本文。
背景技术
众所周知,老化和环境应激引起皮肤的外观、弹性和厚度等变化。具体地,老化和环境因素可导致皮肤病状,包括但不限于细纹、皱纹、干性皮肤、毛孔粗大、皮肤变色、弹性降低、多余毛发、皮肤变薄、紫癜、光化性角化病、瘙痒、湿疹、痤疮、酒渣鼻、红斑、毛细管扩张、光化性毛细管扩张、皮肤癌以及肥大性酒渣鼻。因此,消费者越来越多地转向护肤产品以减少皱纹的出现、使肤色均匀、提供水分、减少眼下黑眼圈的出现等等。
尽管市场上有许多护肤产品改善皮肤外观,但是许多消费者对使用化学合成的产品犹豫不决,他们认为这种产品对环境不友好或不安全。因此,需要含有认为比化学合成产品更加可接受的天然产物的护肤产品。
发明内容
在一些实施方案中,本公开提供了一种重组胶原片段,该重组胶原片段的分子量为约55kDa并且与SEQ ID NO:1所示的氨基酸序列具有至少约85%的序列同一性。在一些实施方案中,该胶原片段具有SEQ ID NO:1所示的氨基酸序列。
在一些实施方案中,本公开提供了一种包含重组胶原片段的组合物,该重组胶原片段的分子量为约55kDa并且与SEQ ID NO:1所示的氨基酸序列具有至少约85%的序列同一性。在一些实施方案中,该组合物包含具有SEQ ID NO:1所示的氨基酸序列的胶原片段。在一些实施方案中,该组合物还包含具有SEQ ID NO:2所示的氨基酸序列的重组胶原片段。在一些实施方案中,该组合物还包含药学上可接受的赋形剂或美容上可接受的赋形剂。
在一些实施方案中,本公开提供了一种治疗皮肤病状的方法,该方法包括将有效量的重组胶原片段局部施用于有需要的受试者,该重组胶原片段的分子量为约55kDa并且与SEQ ID NO:1所示的氨基酸序列具有至少约85%的序列同一性。在一些实施方案中,本公开提供了一种治疗皮肤病状的方法,该方法包括将有效量的胶原片段局部施用于有需要的受试者,该胶原片段具有SEQ ID NO:1所示的氨基酸序列。
在一些实施方案中,本公开提供了一种治疗皮肤病状的方法,该方法包括将有效量的包含重组胶原片段的组合物局部施用于有需要的受试者,该重组胶原片段的分子量为约55kDa并且与SEQ ID NO:1所示的氨基酸序列具有至少约85%的序列同一性。在一些实施方案中,本公开提供了一种治疗皮肤病状的方法,该方法包括将有效量的包含具有SEQ IDNO:1所示的氨基酸序列的胶原片段的组合物局部施用于有需要的受试者。
在一些实施方案中,该皮肤病状选自由以下组成的组:细纹、皱纹、干性皮肤、毛孔粗大、皮肤变色、弹性降低、多余毛发、皮肤变薄、紫癜、光化性角化病、瘙痒、湿疹、痤疮、酒渣鼻、红斑、毛细管扩张、光化性毛细管扩张、皮肤癌、肥大性酒渣鼻以及它们的组合。
在一些实施方案中,将该组合物局部施用于选自由以下组成的组的皮肤区域:面部表面、头皮、颈部、耳朵、肩部、胸部(包括乳房和/或领口)、手臂、手、腿、胃、臀部、腹股沟、背部、脚以及它们的组合。
在一些实施方案中,本公开还提供了产生本文公开的重组胶原片段的方法,该方法包括在遗传工程化的酵母菌株中产生重组胶原片段。在一些实施方案中,酵母为巴斯德毕赤酵母(Pichia pastoris)。在一些实施方案中,该方法包括:在发酵液中发酵遗传工程化的酵母;从发酵液的上清液中回收由遗传工程化的酵母分泌的重组胶原片段;并且任选地,纯化重组胶原片段。在一些实施方案中,该方法包括:在发酵液中发酵遗传工程化的酵母;回收基因工程化的酵母未分泌到上清液中的重组胶原片段;并且任选地,纯化重组胶原片段。在一些实施方案中,回收未分泌到上清液中的重组胶原片段包括从细胞糊浆回收细胞内的重组胶原片段。在一些实施方案中,本文所述的方法还包括冻干所回收的重组胶原片段。
在一些实施方案中,本公开还提供了一种包含重组胶原片段的护肤产品,该重组胶原片段的分子量为约55kDa并且与SEQ ID NO:1所示的氨基酸序列至少约85%的序列同一性,该护肤产品用于减少皱纹的出现、使肤色均匀、提供水分、减少眼下黑眼圈的出现、增加皮肤的胶原含量、增加皮肤密度、改善皮肤紧致度和弹性、改善细纹和皱纹的出现、使皮肤纹理光滑、增加皮肤光泽和亮度、改善松垂皮肤的外观、使皮肤变白或它们的任意组合。在一些实施方案中,本公开还提供了一种包含重组胶原片段的护肤产品,该重组胶原片段具有SEQ ID NO:1所示的氨基酸序列,该护肤产品用于减少皱纹的出现、使肤色均匀、提供水分、减少眼下黑眼圈的出现、增加皮肤的胶原含量、增加皮肤密度、改善皮肤紧致度和弹性、改善细纹和皱纹的出现、使皮肤纹理光滑、增加皮肤光泽和亮度、改善松垂皮肤的外观、使皮肤变白或它们的任意组合。
在一些实施方案中,本公开还提供了:一种包含组合物的护肤产品,该组合物包含重组胶原片段,该重组胶原片段的分子量为约55kDa并且与SEQ ID NO:1所示的氨基酸序列至少约85%的序列同一性;和一种包含组合物的护肤产品,该组合物包含具有SEQ ID NO:1所示的氨基酸序列的重组胶原片段,这些护肤产品用于减少皱纹的出现、使肤色均匀、提供水分、减少眼下黑眼圈的出现、增加皮肤的胶原含量、增加皮肤密度、改善皮肤紧致度和弹性、改善细纹和皱纹的出现、使皮肤纹理光滑、增加皮肤光泽和亮度、改善松垂皮肤的外观、使皮肤变白或它们的任意组合。
在一些实施方案中,本公开还提供了一种治疗有需要的人类受试者的伤口的方法,该方法包括将包含分子量为约55kDa并且与SEQ ID NO:1所示的氨基酸序列具有至少约85%的序列同一性的重组胶原片段的组合物施加于受试者的伤口,其中施加该重组胶原片段诱导人I型胶原、人III型胶原或它们的组合的产生。在一些实施方案中,本公开还提供了一种治疗有需要的人类受试者的伤口的方法,该方法包括将包含具有SEQ ID NO:1所示的氨基酸序列的重组胶原片段的组合物施加于受试者的伤口,其中施加该重组胶原片段诱导人I型胶原、人III型胶原或它们的组合的产生。在一些实施方案中,将胶原片段局部施加于伤口。
在一些实施方案中,本公开还提供了一种含水护肤组合物,该含水护肤组合物包含水和分子量为约55kDa并且与SEQ ID NO:1所示的氨基酸序列具有至少约85%的序列同一性的重组胶原片段、至少一种应激相关蛋白、至少一种细胞壁相关蛋白、至少一种DNA或蛋白合成相关蛋白、至少一种代谢酶和任选地至少一种细胞完整性蛋白。在一些实施方案中,本公开还提供了一种含水护肤组合物,该含水护肤组合物包含水和具有SEQ ID NO:1所示的氨基酸序列的重组胶原片段、至少一种应激相关蛋白、至少一种细胞壁相关蛋白、至少一种DNA或蛋白合成相关蛋白、至少一种代谢酶和任选地至少一种细胞完整性蛋白。在一些实施方案中,本公开还提供了治疗皮肤区域的方法,这些方法包括将有效量的本文所述的含水护肤组合物局部施加于皮肤区域。
在一些实施方案中,该皮肤区域选自由以下组成的组:面部表面、头皮、颈部、耳朵、肩部、胸部(包括乳房和/或领口)、手臂、手、腿、胃、臀部、腹股沟、背部、脚以及它们的组合。在一些实施方案中,该面部表面选自由以下组成的组:前额、眼、口周表面、下巴表面、眶周面、鼻表面、脸颊皮肤表面以及它们的组合。
附图说明
图1是显示如实施例3所述,用于实验023和027的回收细胞内重组胶原片段的实验方法的流程图。
图2A-图2C显示来自实施例3中描述的实验的细胞外重组胶原片段的表达。图2A显示50kDa的胶原片段,并且图2B和图2C显示50kDa和55kDa的胶原片段。
图3A和图3B显示如实施例3所述,在实验023和027期间回收的细胞内胶原的百分比。
图4A-图4C显示与实验023(发酵液)和027(细胞糊浆)的产量相比分泌的胶原(仅上清液)的整体总回收产量。
具体实施方式
定义
描述元件或部件的不定冠词“一个”和“一种”意指存在这些元件或部件中的一个或至少一个元件或部件。尽管通常采用这些冠词来表示修饰的名词是单数名词,但除非在特定情况下另外规定,否则如本文所用,冠词“一个”和“一种”也包括复数形式。类似地,除非在特定情况下另外规定,否则如本文所用,定冠词“该”也表示修饰的名词可为单数或复数。
如本文所用,除非另有明确说明,否则与数值一起使用的术语“约”意指“在规定值的10%以内”。例如,“约5重量%”意指4.5重量%至5.5重量%。
如本文所用,术语“重组胶原”是指使用重组技术制备的至少28种不同的天然存在的胶原类型的家族,包括但不限于I、II、III、IV、V、VI、VII、VIII、IX、X、XI、XII、XIII、XIV、XV、XVI、XVII、XVIII、XIX和XX型胶原。术语胶原包括胶原、胶原片段、胶原样蛋白质、三螺旋胶原、α链、单体、明胶、三聚体以及它们的组合。胶原和胶原样蛋白质的重组表达是本领域已知的(参见,例如,Bell,EP 1232182B1,Bovine collagen and method for producingrecombinant gelatin;Olsen等人,美国专利第6,428,978号和VanHeerde等人,美国专利第8,188,230号,其全文以引用方式并入本文)。在一些实施方案中,本文所述的胶原可使用牛I型胶原制备。胶原的特征在于氨基酸的重复三元组,-(Gly-X-Y)n-,使得胶原中大约三分之一的氨基酸残基为甘氨酸。X通常为脯氨酸,并且Y通常为羟脯氨酸。胶原的结构可由三个不同长度的交织肽链组成。
如本文所用,短语“应激相关蛋白”是指在暴露于环境应激条件后表现出增加的表达的蛋白。环境应激条件包括但不限于感染、炎症、暴露于毒素(例如,乙醇、砷、痕量金属、紫外光等)、饥饿、缺氧或缺水。应激相关蛋白的示例包括但不限于热休克蛋白(Hsp)、硫氧还蛋白、ATP酶和蛋白二硫键异构酶。
如本文所用,短语“细胞壁相关蛋白”是指在细胞壁中发现的并且参与细胞壁的产生的蛋白。细胞壁蛋白的示例包括但不限于外切-1,3-β-葡聚糖酶、内切-β-1,3-葡聚糖酶、糖苷酶、1,3-β-葡聚糖转移酶、几丁质脱乙酰酶和果糖1,6-二磷酸醛缩酶。
如本文所用,短语“DNA或蛋白合成相关蛋白”是指参与新脱氧核糖核酸(“DNA”)的合成、DNA复制、转录、翻译和蛋白折叠的蛋白。DNA或蛋白合成相关蛋白的示例包括但不限于延伸因子1-α、腺苷激酶、60S酸性核糖体蛋白P2-A、核苷二磷酸激酶、核糖体蛋白51、核糖体蛋白L30、核糖体蛋白59、真核翻译起始因子5A、翻译起始因子elF4A、DNA拓扑异构酶2、组蛋白甲基转移酶、S-腺苷-L-甲硫氨酸依赖性tRNA、真核翻译起始因子3亚基1、赖氨酸-tRNA连接酶、DNA指导的RNA聚合酶亚基β、转录因子II和DNA连接酶。
如本文所用,短语“代谢酶”是指调节细胞代谢的酶。代谢酶的示例包括但不限于烯醇化酶I、磷酸丙糖异构酶、超氧化物歧化酶、甘油醛-3-磷酸脱氢酶、钴胺素非依赖性甲硫氨酸合酶、6-磷酸葡糖酸脱氢酶、磷酸转移酶、NADPH依赖性α-酮酰胺还原酶、磷酸甘油酸变位酶、细胞质无机焦磷酸酶、醇脱氢酶、羧肽酶Y抑制剂、磷脂酰甘油/磷脂酰肌醇转移蛋白、细胞质ATP酶、线粒体基质ATP酶、肽基-脯氨酰基顺反异构酶、腺苷激酶、硫醇特异性过氧化物还原酶、鸟氨酸转氨酶、酮醇酸还原异构酶、庚烯酸水合酶、苹果酸脱氢酶、甘油激酶、丙氨酸:乙醛酸转氨酶、核苷二磷酸激酶、几丁质脱乙酰酶、转酮醇酶、NADPH氧化还原酶、果糖1,6-二磷酸醛缩酶、NADH-细胞色素b5还原酶、磷酸甘露糖变位酶、线粒体过氧化物还原酶、3-异丙基苹果酸脱氢酶、硫氧还蛋白过氧化物酶、角鲨烯环氧化酶、苹果酸脱氢酶、粪卟啉原III氧化酶、异柠檬酸脱氢酶[NAD]亚基、NatB N端乙酰转移酶的催化亚基、羧肽酶、三酰基甘油脂肪酶、腺苷高半胱氨酸酶、含黄素的单加氧酶、酸性海藻糖酶、高亲和性甲硫氨酸透性酶、α-1,6甘露糖基转移酶复合体的亚基、腺苷酸环化酶、磷酸转移酶、亚甲基四氢叶酸还原酶、旁路氧化酶、Cu(+2)-转运P-型ATP酶、GTP酶、2-(3-氨基-3羧丙基)组氨酸合酶亚基1、过氧化物酶体生物合成蛋白PAS1、叶酰聚谷氨酸合酶、丙酮酸激酶、丝氨酸/苏氨酸蛋白磷酸酶、蛋白丝氨酸/苏氨酸激酶、β-甘露糖转移酶2、尿素酰胺水解酶、柠檬酸合酶和羊毛甾醇合酶。
如本文所用,术语“细胞完整性蛋白”是指帮助维持细胞的规则结构和功能的蛋白。细胞完整性蛋白的示例包括但不限于丝裂原活化蛋白激酶(MAPK),诸如Ste11p、Ssk2p、Ssk22p、Bck1p、Ste7p、Pbs2p、Mkk1p、Mkk2p、Fus3p、Kss1p、Hog1p、Slt2p和Smk1p。
a.重组胶原
在一些实施方案中,本文所述的重组胶原是重组胶原片段。重组胶原片段可以是能够形成原胶原(三聚体胶原)的天然胶原分子的完整氨基酸序列的片段,或者该片段可以是具有与天然胶原氨基酸序列(或与其原纤维形成区域或与基本上包含[Gly-X-Y]n的链段)有至少70%、80%、90%、95%、96%、97%、98%或99%同一性或相似性的修饰的胶原分子或截短的胶原分子的片段。
片段可由其衍生的示例性胶原序列包括Col1A1、Col1A2和Col3A1的氨基酸序列,诸如以下登录号描述的那些:P02461.4(SEQ ID NO:982;人Col3A1)(www.ncbi.nlm.nih.gov/protein/124056490)、NP_001029211.1(SEQ ID NO:978;牛Col1A1)(www.ncbi.nlm.nih.gov/protein/77404252)、NP_776945.1(SEQ ID NO:979;牛Col1A2)(www.ncbi.nlm.nih.gov/protein/27806257)和NP_001070299.1(SEQ ID NO:980;牛Col3A1)(www.ncbi.nlm.nih.gov/protein/116003881),其以引用方式并入本文。
在一些实施方案中,本文公开的胶原片段可具有约40kDa至约60kDa的分子量。在一些实施方案中,该胶原片段可具有约40kDa、约41kDa、约42kDa、约43kDa、约44kDa、约45kDa、约46kDa、约47kDa、约48kDa、约49kDa、约50kDa、约51kDa、约52kDa、约53kDa、约54kDa、约55kDa、约56kDa、约57kDa、约58kDa、约59kDa或约60kDa的分子量。在一个具体实施方案中,该胶原片段可具有约55kDa的分子量。
在一些实施方案中,本文所述的胶原片段可具有根据SEQ ID NO:1的氨基酸序列。在一些实施方案中,该胶原片段可与SEQ ID NO:1具有至少约70%、至少约75%、至少约80%、约85%、至少约87.5%、至少约90%、至少约92.5%、至少约95%、至少约97.5%、至少约98%、至少约99%或100%的序列同一性或相似性。
SEQ ID NO:1的氨基酸序列是:
MYRNLIIATALTCGAYSAYVPSEPWSTLTPDASLESALKDYSQTFGIAIKSLDADKIKRDSYDVKSGVAVGGLAGYPGPAGPPGPPGPPGTSGHPGSPGSPGYQGPPGEPGQAGPSGPPGPPGAIGPSGPAGKDGESGRPGRPGERGLPGPPGIKGPAGIPGFPGMKGHRGFDGRNGEKGETGAPGLKGENGLPGENGAPGPMGPRGAPGERGRPGLPGAAGARGNDGARGSDGQPGPPGPPGTAGFPGSPGAKGEVGPAGSPGSNGAPGQRGEPGPQGHAGAQGPPGPPGINGSPGGKGEMGPAGIPGAPGLMGARGPPGPAGANGAPGLRGGAGEPGKNGAKGEPGPRGERGEAGIPGVPGAKGEDGKDGSPGEPGANGLPGAAGERGAPGFRGPAGPNGIPGEKGPAGERGAPGPAGPRGAAGEPGRDGVPGGPGMRGMPGSPGGPGSDGKPGPPGSQGESGRPGPPGPSGPRGQPGVMGFPGPKGNDGAPGKNGERGGPGGPGPQGPPGKNGETGPQGPPGPTGPGGDKGDTGPPGPQGLQGLPGTGGPPGENGKPGEPGPKGDAGAPGAPGGKGDAGAPGERGPPAIAGIGGEKAGGFAPYYG
在一些实施方案中,本文所述的胶原片段可具有约350个氨基酸至约600个氨基酸的氨基酸链长,并且可与SEQ ID NO:1具有至少约70%、至少约75%、至少约80%、至少约85%、至少约87.5%、至少约90%、至少约92.5%、至少约95%、至少约97.5%、至少约98%、至少约99%或100%的序列同一性或相似性。在一些实施方案中,本文所述的此类胶原片段可具有约350个氨基酸、约370个氨基酸、约390个氨基酸、约400个氨基酸、约420个氨基酸、约440个氨基酸、约460个氨基酸、约480个氨基酸、约500个氨基酸、约510个氨基酸、约520个氨基酸、约530个氨基酸、约540个氨基酸、约550个氨基酸、约560个氨基酸、约570个氨基酸、约580个氨基酸、约590个氨基酸或约600个氨基酸的长度。
b.包含胶原片段的组合物
在一些实施方案中,本公开提供了一种组合物,该组合物包含一种或多种本文公开的重组胶原片段和至少一种药学上可接受的赋形剂或美容上可接受的赋形剂。在具体实施方案中,该组合物可包含根据SEQ ID NO:1的重组胶原片段和至少一种药学上可接受的赋形剂或美容上可接受的赋形剂。在进一步的实施方案中,该组合物可包含与SEQ ID NO:1具有至少约70%、至少约75%、至少约80%、至少约85%、至少约87.5%、至少约90%、至少约92.5%、至少约95%、至少约97.5%、至少约98%、至少约99%或100%的序列同一性或相似性的重组胶原片段,以及至少一种药学上可接受赋形剂或美容上可接受的赋形剂。在更进一步的实施方案中,该组合物可包含与SEQ ID NO:1具有约85%、约86%、约87%、约88%、约89%、约90%、约91%、约92%、约93%、约94%、约95%、约96%、约97%、约98%、约99%或100%的序列同一性或相似性的重组胶原片段,以及至少一种适合用于膳食补充剂(例如营养补充剂)中的赋形剂。
在一些实施方案中,该组合物可以用约0.1体积%至约20体积%的约0.5重量%至约25重量%的重组胶原片段溶液制备。在这些实施方案的一些实施方案中,该组合物可包含约0.1体积%、约0.2体积%、约0.3体积%、约0.4体积%、约0.5体积%、约0.6体积%、约0.7体积%、约0.8体积%、约0.9体积%、约1体积%、约2体积%、约3体积%、约4体积%、约5体积%、约6体积%、约7体积%、约8体积%、约9体积%、约10体积%、约11体积%、约12体积%、约13体积%、约14体积%、约15体积%、约16体积%、约17体积%、约18体积%、约19体积%或约20体积%的重组胶原片段溶液。在这些实施方案的一些实施方案中,该重组胶原片段溶液包含约0.5重量%、约0.6重量%、约0.7重量%、约0.8重量%、约0.9重量%、约1重量%、约2重量%、约3重量%、约4重量%、约5重量%、约6重量%、约7重量%、约8重量%、约9重量%、约10重量%、约11重量%、约12重量%、约13重量%、约14重量%、约15重量%、约16重量%、约17重量%、约18重量%、约19重量%、约20重量%、约21重量%、约22重量%、约23重量%、约24重量%或约25重量%的重组胶原片段。在这些实施方案的一些实施方案中,该重组胶原片段溶液包含约0.1重量%、约0.2重量%、约0.3重量%、约0.4重量%、约0.5重量%、约0.6重量%、约0.7重量%、约0.8重量%、约0.9重量%、约1重量%、约2重量%、约3重量%、约4重量%、约5重量%、约6重量%、约7重量%、约8重量%、约9重量%、约10重量%、约11重量%、约12重量%、约13重量%、约14重量%、约15重量%、约16重量%、约17重量%、约18重量%、约19重量%、约20重量%、约21重量%、约22重量%、约23重量%、约24重量%或约25重量%的具有根据SEQ ID NO:1的序列的胶原片段。
在一些实施方案中,该组合物可包含约0.0005重量%至约25重量%的重组胶原片段、约0.001重量%至约25重量%的重组胶原片段、约0.01重量%至约25重量%的重组胶原片段、约0.1重量%至约25重量%的重组胶原片段、约0.5重量%至约20重量%的重组胶原片段、约0.7重量%至约17重量%的重组胶原片段、约1重量%至约15重量%的重组胶原片段、约2重量%至约12重量%的重组胶原片段、约2重量%至约10重量%的重组胶原片段、约3重量%至约9重量%的重组胶原片段、约4重量%至约8重量%的重组胶原片段或约5重量%至约7重量%的重组胶原片段。在一些实施方案中,该组合物可包含约0.0005重量%、约0.001重量%、约0.01重量%、约0.1重量%、约0.2重量%、约0.3重量%、约0.4重量%、约0.5重量%、约0.6重量%、约0.7重量%、约0.8重量%、约0.9重量%、约1重量%、约2重量%、约3重量%、约4重量%、约5重量%、约6重量%、约7重量%、约8重量%、约9重量%、约10重量%、约11重量%、约12重量%、约13重量%、约14重量%、约15重量%、约16重量%、约17重量%、约18重量%、约19重量%、约20重量%、约21重量%、约22重量%、约23重量%、约24重量%或约25重量%的重组胶原片段。在一些实施方案中,该组合物可包含约0.0005重量%、约0.001重量%、约0.01重量%、约0.1重量%、约0.2重量%、约0.3重量%、约0.4重量%、约0.5重量%、约0.6重量%、约0.7重量%、约0.8重量%、约0.9重量%、约1重量%、约2重量%、约3重量%、约4重量%、约5重量%、约6重量%、约7重量%、约8重量%、约9重量%、约10重量%、约11重量%、约12重量%、约13重量%、约14重量%、约15重量%、约16重量%、约17重量%、约18重量%、约19重量%、约20重量%、约21重量%、约22重量%、约23重量%、约24重量%或约25重量%的具有根据SEQ ID NO:1的序列的胶原片段。
c.护肤
在一些实施方案中,本文所述的组合物可用于改善皮肤和/或其附属体的美学外观,例如皮肤的表面外观和/或纹理。在一些实施方案中,本文所述的组合物可以配制用于身体和面部、手和脚,包括用作对眼部区域、指甲和毛发的治疗。术语“表面外观”意指皮肤和/或头皮中的视觉和/或触觉不规则性,包括皱纹和细纹、前额上和眉毛间的空间中的表情纹、嘴周围的皱纹和/或细纹和/或嘴唇周围区域和上唇区域(位于上唇和鼻之间的区域)松弛、肤色不均匀(雀斑、光化性雀斑样痣)、毛孔的外观和/或可见度、皮肤的纸状外观、皮肤微起伏中的缺陷诸如水痘或痤疮疤痕、油性皮肤的缺陷(发光外观等)。术语“皮肤纹理”可以指松弛、松垮、不太紧致、不太有弹性的皮肤和/或已经松垂的皮肤。
在一些实施方案中,本文所述的组合物可用于改善皮肤的美学外观,包括改善表情纹的外观。表情纹通过由下面的肌肉施加在皮肤上的应力的作用产生。年龄和环境因素(诸如暴露于阳光)可加深表情纹并使表情纹持久。表情纹的特征在于,在由鼻(鼻沟)、嘴(口周纹和所谓的苦味纹)和眼睛(鱼尾纹)形成的孔周围皮肤肌肉所在的区域,还有眉毛之间(眉间皱纹或狮子纹)和前额上存在沟。
在一些实施方案中,本文所述的组合物可用于改善皮肤的美学外观和/或毛孔的可见度。毛孔的可见度可归因于皮脂过量、老化、紧致度损失、松弛、应力、疲劳、不适当的卫生、气候因素或它们的任意组合。本文所述的组合物可使毛孔收紧,使它们较不可见。
在一些实施方案中,本文所述的组合物可用于改善皮肤的纸状外观和皮肤触摸行为。具体地,较老的皮肤可以在视觉上呈现卷烟纸的外观,使其具有类似于纸莎草纸的外观。在老年人的面部和手背上可以看到皮肤的纸状外观。
在一些实施方案中,本文所述的组合物可以是用于面部、手、脚或身体保护、治疗或护理的组合物,例如,日霜、晚霜、卸妆乳霜、防晒组合物、用于皮肤保护或护理的身体乳、晒后乳、护肤洗剂、凝胶、泡沫、人工晒黑组合物和须后组合物。在一些实施方案中,本文所述的组合物可以配制为例如溶液、悬浮液、洗剂、乳霜、精华液、凝胶、香膏、凝胶、油、霜包油、胶束水、面部喷雾、面部精华、遮瑕膏或肤色修正配方、调色剂(基于水和/或醇)、涂剂、抛光剂、棒、铅笔、喷雾剂、气溶胶、软膏、清洁液体洗涤剂、固体棒、香波、护发素、头发定型产品、糊剂、泡沫、粉末、摩丝、香膏、剃须膏、擦拭物、条、贴片、伤口敷料、粘性绷带、水凝胶、成膜产品、面部和皮肤面膜、化妆品(例如粉底、眼线膏、眼影)、去角质剂、除臭剂和止汗剂等。本文提供了示例性调配物。
在一些实施方案中,本文所述的组合物可以是美容组合物,并且该至少一种赋形剂可以是美容上可接受的赋形剂。美容上可接受的赋形剂是适合用于美容产品中的赋形剂。示例性的美容上可接受的赋形剂描述如下。
在一些实施方案中,美容组合物可包含通常用于美容产品例如护肤、眼部护理、指甲护理和毛发护理产品中的成分。这些成分可以包括但不限于皂、抗微生物剂、抗炎剂、增湿剂、蜡醇、水合剂、增湿剂、渗透促进剂、乳化剂、天然或合成油、溶剂、脂肪、表面活性剂、洗涤剂、胶凝剂、润肤剂、抗氧化剂、香味剂、涂剂、抛光剂、填充剂、增稠剂、蜡、气味吸收剂、染料、着色剂、粉末、粘度控制剂、麻醉剂、止痒剂、植物提取物、调理剂、暗化剂或增白剂、保湿剂、云母、矿物质、多酚、硅酮或硅酮衍生物(诸如二甲聚硅氧烷)、防晒剂、维生素、植物药、醇(诸如变性醇和乙醇)、多元醇、多元醇醚以及《国际化妆品成分词典和手册》第13版(2009)中列出的其他成分,该文献的全部内容以引用方式并入本文。在某些实施方案中,给定的成分可以执行多于一种功能并且可以属于多于一个类别。
在一些实施方案中,本文所述的组合物可以是治疗组合物,并且该至少一种赋形剂可以是治疗上可接受的赋形剂。治疗组合物可用于治疗一种或多种病状,诸如减少或预防疤痕组织的形成、促进愈合、促进组织再生、使局部炎症最小化、使组织排斥最小化和/或增强皮肤和/或毛发移植物整合。治疗上可接受的赋形剂是可用作活性物质的媒介物或介质的赋形剂,并且包括通常用于治疗组合物(即,可用于治疗一种或多种病状的组合物)中的赋形剂。示例性的治疗上可接受的赋形剂描述如下。
本文所述的组合物还可包括一种或多种以下的附加组分。示例性考虑的附加成分如下所述;然而,本公开不限于这些示例性的附加成分。
在一些实施方案中,本文所述的组合物还可包含一种或多种抗皱剂。抗皱剂是当组合物与皱纹皮肤区域(例如身体或面部,包括眼部区域)接触时引起皮肤的某些酶的合成和/或活性增加的化合物,这些酶会减少皱纹和/或细纹的外观。示例性抗皱剂包括但不限于脱屑剂、抗糖化剂、一氧化氮合酶抑制剂、肌肉松弛剂和/或抗皮肤皱缩剂、抗自由基剂以及它们的混合物。
可包括在本文所述的组合物中的另外的示例性抗皱剂包括但不限于腺苷及其衍生物、视黄醇及其衍生物(例如视黄醇棕榈酸酯)、抗坏血酸及其衍生物(例如抗坏血酸磷酸镁和抗坏血酸葡糖苷)、生育酚及其衍生物(例如醋酸生育酚)、烟酸及其前体(例如烟酰胺)、泛醌、谷胱甘肽及其前体(例如L-2-氧代噻唑烷-4-羧酸)、C-糖苷化合物(也称为C-糖基化合物)及其衍生物(例如商品名为PRO-XYLANE的β-C-木糖基衍生物、植物提取物(例如,海茴香提取物和橄榄叶提取物)、植物蛋白及其水解产物(例如,水稻或大豆蛋白水解产物)、藻类提取物(例如,昆布藻类提取物)、细菌提取物、皂苷元(例如,薯蓣皂苷元)、薯蓣提取物(例如,野山药提取物)、α-羟酸、β-羟酸(例如,水杨酸和5-(正辛酰基)水杨酸)、寡肽和假二肽及它们的酰化衍生物(例如,{2-[乙酰基(3-(三氟甲基)苯基)氨基]-3-甲基丁酰基氨基}乙酸)、脂肽(例如,可从Croda获得的MATRIXYL 3000))、番茄红素、锰盐、镁盐(例如,葡糖酸盐)和任何前述物质的组合。
示例性的腺苷衍生物包括但不限于2'-脱氧腺苷;2',3'-异亚丙基腺苷;丰加霉素(toyocamycin),1-甲基腺苷;N-6-甲基腺苷、腺苷N-氧化物、6-甲基-巯基嘌呤核苷和6-氯嘌呤核苷。其他腺苷衍生物包括腺苷受体激动剂,包括苯基异丙基腺苷(“PIA”)/1-甲基异鸟苷、Ns-环己基腺苷(CHA)、N6-环戊基腺苷(CPA)、2-氯-Ns-环戊基-腺苷、2-氯腺苷、N6-苯基腺苷、2-苯基氨基腺苷、MECA、Ne-苯乙基腺苷、2-对-(2-羧乙基)苯乙基氨基-5'-N-乙基甲酰胺基-腺苷(CGS-21680)、(N-乙基甲酰胺基)腺苷-S-(NECA)、5'-(N-环丙基甲酰胺基)腺苷、DPMA(PD 129,944)和腺苷地尔(metrifudil)。
在一些实施方案中,本文所述的组合物可包含一种或多种增加腺苷的细胞内浓度的腺苷衍生物,例如赤-9-(2-羟基-3-壬基)腺嘌呤(“EHNA”)、碘代杀结核菌素或它们的组合。本文考虑的另外的腺苷衍生物包括腺苷盐和腺苷的烷基酯。
在一些实施方案中,该组合物还可包含一种或多种珠光剂。珠光剂是任何形状的彩虹颗粒,尤其是由某些贝类在它们的壳中产生的。可替代地,珠光剂可以合成,即人工制得。珠光剂可选自白色珠光剂,诸如但不限于用氧化钛或用氯氧化铋覆盖的云母;有色珠光剂,诸如但不限于基于氯氧化铋的珠光剂;用氧化铁覆盖的氧化钛包被的云母;尤其是用铁蓝或氧化铬覆盖的氧化钛包被的云母;或用有机颜料覆盖的氧化钛包被的云母。
在一些实施方案中,该组合物还可包含一种或多种羟酸。羟酸的示例包括β羟酸,诸如水杨酸、乙酰水杨酸等。适合用于该组合物中的其他示例性羟酸包括柠檬酸、乙醇酸、羟基己酸、羟基辛酸、乳酸、苹果酸、酒石酸、多羟酸(包括葡糖酸内酯)以及它们的任意组合。
在一些实施方案中,该组合物还可包含一种或多种乳化剂。乳化剂防止不同的成分(诸如油和水)在乳液中分离。合适的乳化剂包括但不限于:聚山梨醇酯、月桂醇聚醚-4、鲸蜡基硫酸钾、辛酸甘油酯及它们的任意组合。
在一些实施方案中,该组合物还可包含一种或多种抗微生物剂。合适的抗微生物剂包括但不限于:辛酰基甘油醚、苯扎氯胺、苄索氯铵和氯二甲苯酚(PCMX)、茶树油、金缕梅油、迷迭香油、柠檬油及它们的任意组合。
在一些实施方案中,该组合物还可包含一种或多种保湿剂(保水剂)以改善皮肤中的水分水平。适合用于本文所述的组合物中的保湿剂的非限制性示例在WO 98/22085、WO98/18444和WO 97/01326中有描述,并且包括:氨基酸及其衍生物,诸如脯氨酸和精氨酸天冬氨酸盐、1,3-丁二醇、丙二醇、戊二醇、水、软毛松藻提取物、肌酸酐、双甘油、生物糖胶-1、葡糖胺盐、葡糖醛酸盐、谷氨酸盐、甘油的聚乙二醇醚(例如甘油聚醚20)、甘油、甘油单丙氧基化物、糖原、己二醇、蜂蜜、氢化淀粉水解产物、水解粘多糖(诸如黄原胶和生物糖胶-1)、肌醇、角蛋白氨基酸、糖胺聚糖、甲氧基PEG 10、甲基葡糖醇聚醚-10和甲基葡糖醇聚醚-20、甲基葡萄糖、3-甲基-1,3-丁二醇、N-乙酰基葡糖胺盐、聚乙二醇及其衍生物(诸如PEG 15丁二醇、PEG 4、PEG 5季戊四醇、PEG 6、PEG 8、PEG 9)、丙二醇、季戊四醇、1,2戊二醇、PPG-1甘油醚、2-吡咯烷酮-5-羧酸(包括其盐和酯)、糖类同分异构体、丝胶、丝氨基酸、乙基玻尿酸钠、透明质酸钠、聚天冬氨酸钠、聚谷氨酸钠、辛二醇、山梨醇聚醚20、山梨醇聚醚6、糖和糖醇及其衍生物,诸如葡萄糖、甘露糖和聚甘油山梨糖醇、海藻糖、三甘油、三羟甲基丙烷、三(羟甲基)氨基甲烷盐和酵母菌提取物以及它们的混合物。
适合用于本文的其他保湿剂包括选自由以下组成的组的多元醇:甘油、双甘油、丙三醇、赤藓糖醇、阿拉伯糖醇、木糖醇、核糖醇、甘露糖醇、山梨糖醇、半乳糖醇、岩藻糖醇、麦芽糖醇、甘露糖、肌醇、三乙二醇、吡咯烷酮羧酸钠(PCA)、PCA锌以及它们的衍生物和混合物。
在一些实施方案中,该组合物还可包含胶凝剂,该胶凝剂包含基于聚丙烯酰胺的聚合物。基于聚丙烯酰胺的聚合物除了是聚丙烯酰胺本身以外,还可以是其衍生物,并且可以是多种类型的聚合物的混合物,并且还可以是以丙烯酰胺及其衍生物为单体的共聚物。胶凝剂可用于为皮肤提供良好的外观,为皮肤提供清凉的感觉,并且为皮肤提供清爽不发粘的感觉。在一些实施方案中,胶凝剂可包括一种或多种颜料,或一种或多种填充剂,包括:无机颜料(包括体质颜料、着色颜料和增白颜料)、有机颜料、珠光光泽颜料、大分子粉末、功能颜料、滑石、云母、高岭土、碳酸钙、碳酸镁、硅酸酐、硅酸铝、硅酸镁、硅酸钙、氧化铝、硫酸钡、红铁氧化物、黄铁氧化物、黑铁氧化物、氧化铬、群青蓝、普鲁士蓝、炭黑、氧化锌、云母钛、鱼鳞片、氯氧化铋、氮化硼、尼龙粉末、蚕丝粉末、卡波姆、焦油颜料、天然颜料和氧化钛,诸如无定形或金红石型和/或锐钛矿型晶体。
在一些实施方案中,该组合物可包含耐水和耐油的颜料和/或填充剂,并且还可包含任何常规使用的防水剂和/或防油剂以赋予颜料防水性和防油性,例如氟化合物。常规使用并且可充当防水剂和防油剂的代表性氟化合物包括具有全氟烷基的化合物,诸如全氟烷基磷酸酯、全氟烷基硅烷、全氟烷基硅氮烷、聚六氟环氧丙烷、含全氟烷基的有机硅氧烷、全氟聚醚、全氟醇、全氟烷基丙烯酸酯聚合物及它们的衍生物。全氟烷基磷酸酯可在凝胶组合物的配方内提供均匀且稳定的颜料分散,并且全氟烷基硅烷可具有与其他美容成分的优异相容性。另外,可以使用由Asahi Glass以AsahiGuard AG530生产上市的全氟烷基磷酸酯-二乙醇胺盐,和全氟烷基硅烷偶联剂,诸如Shin-Etsu Silicone的LP-IT和LP-4T。
代表性的胶凝剂包括但不限于由Seppic以商品名Sepigel 305、Sepigel501和Sepigel 600生产上市的那些胶凝剂。Sepigel 305是含有大约40%聚丙烯酰胺、大约24%-C13-C14异链烷烃和大约6%月桂醇聚醚-7(此处,月桂醇聚醚-7是具有式C12H25--(OCH2CH2)n--OH的非离子表面活性剂,其中n的平均值为7)的混合物。Sepigel 600是丙烯酰胺/丙烯酰胺-2-丙磺酸盐共聚物、异十六烷和聚山梨醇酯80(聚氧乙烯山梨醇酐单油酸酯(20EO))的混合物。包含基于聚丙烯酰胺的聚合物的合适胶凝剂公开于EP 0503 853(Scott Bader Company Ltd.)中,其公开内容以引用方式并入本文。
在一些实施方案中,该组合物还可包含透明质酸(HA)。在一些实施方案中,HA可以呈非交联状态。在一些实施方案中,HA可以呈交联状态。与胶原类似,HA是人体组织的重要结构组分。透明质烷,也称为透明质酸(HA),是一种非硫酸化的糖胺聚糖,其广泛地分布在人体的结缔组织、上皮组织和神经组织中。透明质烷在皮肤的不同层中是丰富的,其中它具有多种功能,例如,确保良好的水合作用、协助细胞外基质的组织、充当填充材料;及参与组织修复机制。然而,随着年龄的增长,存在于皮肤中的透明质烷的量减少。
在一些实施方案中,该组合物还可包含蜡状脂质,例如神经酰胺。神经酰胺有助于产生防止渗透性的屏障,这有助于防止干燥和刺激,并且还可以保护表皮免受环境损害。
在一些实施方案中,该组合物还可包含至少一种维生素。在一些实施方案中,该组合物还可包含维生素A或维生素A衍生物。维生素衍生物的示例包括但不限于类视黄醇诸如视黄醛、视黄酸、视黄酸酯、视黄醇酯、视黄醇、维甲酸、异维甲酸、阿达帕林(adapalene)、他扎罗汀(tazarotene)等。术语“类视黄醇”包括类视黄醇的顺式和反式衍生物(例如全反式视黄酸、13-顺式视黄酸、13-反式视黄酸和9-顺式视黄酸)。
在一些实施方案中,该组合物还可包含维生素C或其衍生物,例如抗坏血酸、抗坏血酸酯(例如抗坏血酸四己基癸酯)等。
在一些实施方案中,该组合物还可包含维生素B,例如生物素(即维生素B7)、烟酰胺等。
在一些实施方案中,该组合物还可包含维生素E,例如α-生育酚、β-生育酚、γ-生育酚和σ-生育酚及它们相关的相应生育三烯酚等。
在一些实施方案中,该组合物还可包含维生素K及其衍生物。
对于本公开考虑到了可被适当地配制为局部组合物的任何维生素、维生素类似物或其衍生物。
在一些实施方案中,本文公开的组合物还可包含一种或多种增稠试剂。增稠试剂,即结构增效剂,能够使颜料悬浮和/或在组合物中增加粘度。适于本发明组合物的增稠剂和/或结构增效剂包括但不限于有机改性粘土、煅制二氧化硅、三羟基硬脂精、硅酮凝胶或硅酮弹性体、丙烯酰二甲基牛磺酸铵/VP共聚物、丙烯酸酯/丙烯酸C10-30烷基酯交联聚合物以及它们的混合物。
合适的有机改性粘土包括但不限于锂蒙脱石、膨润土、绿土和蒙脱石粘土的有机改性型式(诸如以商品名从Elementis Specialties销售的那些,以商品名从Sud-Chemie销售的那些和以商品名/>从Southern ClayProducts销售的那些)。亲水改性的煅制二氧化硅包括但不限于WACKER/>N20和T30级(Wacker-Chemie AG),以及商品名为/>(Evonik)的亲水级。硅酮凝胶或硅酮弹性体包括但不限于来自Shin-Etsu Silicones的“KSG”增稠系列(KSG-15、KSG-16、KSG-18、KSG-41、KSG-42、KSG-43、KSG-44),来自Dow Corning的DOW/>9040、9041、9045和9546硅酮弹性体共混物,来自Momentive Performance Materials的SFE839TM和VelvesilTM硅酮凝胶,以及来自Wacker-Chemie AG的/>RG-100。
在一些实施方案中,本文公开的组合物还可以包含一种或多种脂溶性/脂分散性成膜剂。适合用于本文的脂溶性/脂分散性成膜剂包括但不限于有机硅酮树脂(例如,三甲基甲硅烷氧基硅酸酯,诸如来自GE Silicones的SRI 000)和有机硅酮树脂的共聚物(例如,二异硬脂基三羟甲基丙烷甲硅烷氧基硅酸酯,诸如来自GE Silicones的SF1318);氟化硅酮树脂;丙烯酸类和/或基于乙烯基的聚合物或共聚物,包括硅酮和/或氟化型式(例如,来自Shin-Etsu Silicones的“KP”系列的硅酮丙烯酸酯,和3MTM硅酮“Plus”聚合物VS70和SA70);聚氨酯(例如,来自Alzo International的羟基酯甘油三酯衍生的Poly系列);聚酯(例如,来自Inolex Chemical Company的/>系列的聚合聚酯);以及它们的混合物。
在一些实施方案中,本文公开的组合物还可包含一种或多种着色剂。适合用于本文的着色剂包括所有无机和有机色素/颜料,包括适合用于美容组合物中的矿物或珠光颜料。此类着色剂包括具有或不具有表面涂层或处理的那些。着色剂可增强组合物的着色和/或光散射和/或光反射效果。
在一些实施方案中,本文公开的组合物还可包含一种或多种防晒剂,例如矿物和/或物理防晒剂。防晒剂可阻断UVA和/或UVB辐射。示例性的UVA防晒剂包括但不限于阿伏苯宗(avobenzone)、对苯二亚甲基二樟脑磺酸、双二磺唑二钠、苯二苯并咪唑四磺酸二钠、二乙基氨基羟基苯甲酰基己基苯甲酸酯、双二乙基氨基羟基苯甲酰基苯甲酸酯、双苯并噁唑基苯基乙基己基氨基三嗪以及它们的组合。
示例性的UVB的防晒剂包括但不限于奥克立林(octocrylene)、奥西诺酯(octinoxate)、辛水杨酯(octisalate)、胡莫柳酯(homosalate)、恩索利唑(ensulizole)、乙基己基三嗪酮、恩扎卡明(enzacamene)、阿米洛酯(amiloxate)、二乙基己基丁酰胺基三嗪、亚苄基丙二酸聚硅氧烷、帕地马酯-O、三乙醇胺水杨酸盐、西诺沙酯(cinoxate)、对氨基苯甲酸及它们的衍生物以及它们的组合。
吸收UVA和UVB辐射的示例性防晒剂例如氧苯酮(oxybenzone)、meradiate、二氧化钛、氧化锌、双-奥克三唑、贝莫曲辛(bemtrizinol)、甲酚曲唑三硅氧烷(drometrizoletrisiloxane)、舒利苯酮(sulisobenzone)、二羟苯宗(dioxybenzone)或它们的组合。
具体的合适的防晒剂包括但不限于对氨基苯甲酸、其盐及其衍生物(乙基、异丁基、甘油酯、对二甲基氨基苯甲酸、邻氨基苯甲酸酯(即,邻-氨基苯甲酸酯、甲酯、薄荷酯、苯酯、苄酯、苯乙酯、芳樟酯、萜品酯和环己烯基酯)、水杨酸酯(戊酯、苯酯、苄酯、薄荷酯、甘油酯和二丙二醇酯)、肉桂酸衍生物(甲酯和苄基酯、α-苯基肉桂腈、丁基肉桂酰丙酮酸酯)、二羟基肉桂酸衍生物(伞形酮、甲基伞形酮、甲基乙酰-伞形酮)、三羟基肉桂酸衍生物(七叶亭、甲基七叶亭、瑞香素和葡糖苷、七叶苷和瑞香苷)、烃(二苯基丁二烯、茋)、二亚苄基丙酮和亚苄基苯乙酮、萘酚磺酸盐(2-萘酚-3,3-二磺酸和2-萘酚-6,8-二磺酸的钠盐)、ci羟基萘甲酸及其盐、邻羟基联苯基二磺酸盐和对羟基联苯基二磺酸盐、香豆素衍生物(7-羟基香豆素、7-甲基香豆素、3-苯基香豆素)、二唑(2-乙酰基-3-溴吲唑、苯基苯并噁唑、甲基萘噁唑、各种芳基苯并噻唑)、奎宁盐(硫酸氢盐、硫酸盐、氯化物、油酸盐和鞣酸盐)、喹啉衍生物(8-羟基喹啉盐、2-苯基喹啉)、羟基或甲氧基取代的二苯甲酮、尿酸和维利酸(vilouricacid)、鞣酸及其衍生物(例如六乙基醚)、(丁基卡必醇)(6-丙基胡椒基)醚、氢醌、二苯甲酮(羟苯、磺异苯酮、二羟苯甲酮、苯酰间苯二酚、2,2,4,4'-四羟基二苯甲酮、2,2'-二羟基-4,4'-二甲氧基二苯甲酮、奥他苯酮、4-异丙基二苯甲酰基甲烷、丁基甲氧基二苯甲酰基甲烷、依托立林(etocrylene)和4-异丙基-二苯甲酰基甲烷、二氧化钛、氧化铁、氧化锌及它们的混合物。其他美容上可接受的防晒剂和浓度(总美容防晒组合物的重量百分比)包括二乙醇胺甲氧基肉桂酸酯(10%或更少)、乙基-双(羟基丙基)氨基苯甲酸酯(5%或更少)、氨基苯甲酸甘油酯(3%或更少)、4-异丙基二苯甲酰基甲烷(5%或更少)、4-甲基亚苄基樟脑(6%或更少)、对苯二亚甲基二樟脑磺酸(10%或更少)和磺异苯酮(也称为二苯甲酮-4,10%或更少)。在一些实施方案中,本文公开的组合物还可包含D-天冬氨酸和/或D-丙氨酸及它们的任何盐。如本文所用,术语D-天冬氨酸和D-丙氨酸的“衍生物”指示通过它们的氨基、羧基或侧链与任何有机基团共价结合的D-天冬氨酸和D-丙氨酸分子,条件是不削弱D-天冬氨酸和D-丙氨酸促进胶原产生的作用。示例性有机基团包括但不限于保护基团,诸如N-苯基乙酰基和4,4'-二甲氧基三苯甲基(DMT)基团;生物聚合物,诸如蛋白、肽、糖、脂质和核酸;合成聚合物,诸如聚苯乙烯、聚乙烯(polyethylene)、聚乙烯(polyvinyl)、聚丙烯和聚酯;和官能团,诸如酯基。酯基可包括例如脂族酯,诸如甲酯和乙酯;和芳族酯。
在一些实施方案中,该组合物还可包含一种或多种通用护肤添加剂,例如调理剂诸如硅氧烷。在一些实施方案中,该组合物还可包含一种或多种鲨鱼肝油,例如角鲨烷和/或角鲨烯。在一些实施方案中,该组合物还可包含由微藻类产生的一种或多种多糖,例如,微藻酸(alguronic acid)。
在一些实施方案中,该组合物还可包含至少一种防腐剂。在一些实施方案中,该至少一种防腐剂可以是季铵化合物、卤代酚、山梨酸、山梨酸钾、苯甲酸、苯甲酸钠、柠檬酸钠、茴香酸钠、辛酰氧肟酸、乙酰丙酸钠、苯氧乙醇或它们的组合。
本文所述组合物的pH可在约4至约8、约4.7至约5.5、约5至约7、约6至约7、约6.1至约6.8或约6.4至约6.6的范围内。
在一些实施方案中,本文所述的组合物可以是皮肤填充剂组合物,例如可注射的皮肤填充剂组合物。皮肤填充剂通常由胶原制成并且可以任选地包含透明质酸(HA)。皮肤填充剂组合物可适合用于面部和身体,包括例如眼周、面颊上或面颊周围、领口上或领口周围、手上或手周围、指甲上或指甲周围、耳朵上或耳朵周围(包括耳垂上)、腿上或腿周围以及脚上或脚周围。
在一些实施方案中,本文所述的组合物可与微针阵列一起使用,诸如包括在片或贴剂中的阵列。微针阵列可包括长度足以穿透皮肤穿过角质层并进入活性表皮中的多个微针。在一些实施方案中,可能期望将多肽递送至表皮/真皮连接区域以用于美容或治疗目的。
在一些实施方案中,本文所述的组合物可与微针片或贴剂一起使用。微针和微针贴剂适于将胶原递送到面部和身体上的人类皮肤的表皮和真皮中,包括例如眼睛、面颊、嘴唇、领口和手。在一些实施方案中,用于以靶向方式将组合物递送到表皮和真皮中的微针是可注射微针、药物包被的金属微针或具有可溶解尖端的微针。关于微针的示例性方法和公开内容可见于例如Aditya等人,Kinetics of collagen microneedledrug deliverysystem,Journal of Drug Delivery Science and Technology,第52卷,第618-623页(2019年8月)和Sun等人,Transdermal Delivery of Functional Collagen ViaPolyvinylpyrrolidone Microneedles,Ann.Biomed.Eng.,43(12):2978-2990(2015),这些文献中的每一者均以引用方式并入。
根据本公开的组合物可包含本文所述的重组胶原片段、至少一种应激相关蛋白、至少一种细胞壁相关蛋白、至少一种DNA或蛋白质合成相关蛋白、至少一种代谢酶、水和任选地至少一种细胞完整性蛋白。
在一些实施方案中,该组合物可包含应激相关蛋白。在某些实施方案中,应激相关蛋白可以是参与蛋白输入至内质网的ATP酶、参与蛋白折叠的ATP酶、蛋白质二硫键异构酶、Hsp90、Hsp90共伴侣、硫氧还蛋白、细胞质ATP酶、蛋白质二硫键异构酶或它们的组合。
在一些实施方案中,该组合物可包含细胞壁相关蛋白。在某些实施方案中,细胞壁相关蛋白可以是主要的外切-1,3-β-葡聚糖酶、内切-β-1,3-葡聚糖酶、糖苷酶、1,3-β-葡聚糖转移酶、几丁质脱乙酰酶、果糖1,6-二磷酸醛缩酶或它们的组合。
在一些实施方案中,该组合物可包含DNA或蛋白合成蛋白。在某些实施方案中,DNA或蛋白合成蛋白可以是延伸因子1-α、腺苷激酶、60S酸性核糖体蛋白P2-A、核苷二磷酸激酶、核糖体蛋白51、核糖体蛋白L30、核糖体蛋白59、真核翻译起始因子5A、翻译起始因子elF4A、DNA拓扑异构酶2、组蛋白甲基转移酶、S-腺苷-L-甲硫氨酸依赖性tRNA、真核翻译起始因子3亚基1、赖氨酸-tRNA连接酶、DNA指导的RNA聚合酶亚基β、转录因子II、DNA连接酶以及它们的组合。
在一些实施方案中,该组合物可包含代谢酶。在某些实施方案中,代谢酶可以是烯醇化酶I、磷酸丙糖异构酶、超氧化物歧化酶、甘油醛-3-磷酸脱氢酶、钴胺素非依赖性甲硫氨酸合酶、6-磷酸葡糖酸脱氢酶、磷酸转移酶、NADPH依赖性α-酮酰胺还原酶、磷酸甘油酸变位酶、细胞质无机焦磷酸酶、醇脱氢酶、羧肽酶Y抑制剂、磷脂酰甘油/磷脂酰肌醇转移蛋白、细胞质ATP酶、线粒体基质ATP酶、肽基-脯氨酰基顺反异构酶、腺苷激酶、硫醇特异性过氧化物还原酶、鸟氨酸转氨酶、酮醇酸还原异构酶、庚烯酸水合酶、苹果酸脱氢酶、甘油激酶、丙氨酸:乙醛酸转氨酶、核苷二磷酸激酶、几丁质脱乙酰酶、转酮醇酶、NADPH氧化还原酶、果糖1,6-二磷酸醛缩酶、NADH-细胞色素b5还原酶、磷酸甘露糖变位酶、线粒体过氧化物还原酶、3-异丙基苹果酸脱氢酶、硫氧还蛋白过氧化物酶、角鲨烯环氧化酶、苹果酸脱氢酶、粪卟啉原III氧化酶、异柠檬酸脱氢酶[NAD]亚基、NatB N端乙酰转移酶的催化亚基、羧肽酶、三酰基甘油脂肪酶、腺苷高半胱氨酸酶、含黄素的单加氧酶、酸性海藻糖酶、高亲和性甲硫氨酸透性酶、α-1,6甘露糖基转移酶复合体的亚基、腺苷酸环化酶、磷酸转移酶、亚甲基四氢叶酸还原酶、旁路氧化酶、Cu(+2)-转运P-型ATP酶、羧肽酶、三酰甘油脂肪酶、腺苷高半胱氨酸酶、含黄素的单加氧酶、酸性海藻糖酶、高亲和性甲硫氨酸透性酶、α-1,6甘露糖基转移酶复合物的亚基、腺苷酸环化酶、磷酸转移酶、亚甲基四氢叶酸还原酶、交替氧化酶、Cu(+2)-转运P型ATP酶、GTP酶、2-(3-氨基-3羧丙基)组氨酸合酶亚基1、过氧化物酶体生物合成蛋白PAS1、叶酰聚谷氨酸合酶、丙酮酸激酶、丝氨酸/苏氨酸蛋白磷酸酶、蛋白丝氨酸/苏氨酸激酶、β-甘露糖转移酶2、尿素酰胺水解酶、柠檬酸合酶、羊毛甾醇合酶或它们的组合。
在一些实施方案中,该组合物可包含约0.5重量%至约20重量%的至少一种应激相关蛋白、约0.7重量%至约17重量%、约1重量%至约15重量%的至少一种应激相关蛋白、约2重量%至约13重量%的至少一种应激相关蛋白、约2重量%至约11重量%的至少一种应激相关蛋白、约3重量%至约10重量%的至少一种应激相关蛋白、约4重量%至约9重量%的至少一种应激相关蛋白、约5重量%至约8重量%的至少一种应激相关蛋白、或约6重量%至约7重量%的至少一种应激相关蛋白。在一些实施方案中,该组合物可以包含按重量计约0.5%、约0.6%、约0.7%、约0.8%、约0.9%、约1%、约2%、约3%、约4%、约5%、约6%、约7%、约8%、约9%、约10%、约11%、约12%、约13%、约14%、约15%、约16%、约17%、约18%、约19%或约20%的至少一种应激相关蛋白。
在一些实施方案中,该组合物可包含约0.1重量%至约20重量%的至少一种细胞壁相关蛋白、约0.2重量%至约17重量%的至少一种细胞壁相关蛋白、约0.3重量%至约15重量%的至少一种细胞壁相关蛋白、约0.4重量%至约13重量%的至少一种细胞壁相关蛋白、约0.5重量%至约10重量%的至少一种细胞壁相关蛋白、约1重量%至约9重量%的至少一种细胞壁相关蛋白、约1重量%至约8重量%的至少一种细胞壁相关蛋白、约1.5重量%至约7.5重量%的至少一种细胞壁相关蛋白、约2重量%至约7重量%的至少一种细胞壁相关蛋白、约2.5重量%至约6.5重量%的至少一种细胞壁相关蛋白、约3重量%至约6重量%的至少一种细胞壁相关蛋白、约3.5重量%至约5.5重量%的至少一种细胞壁相关蛋白或约4重量%至约5重量%的至少一种细胞壁相关蛋白。在一些实施方案中,该组合物可包含按重量计约0.1%、约0.2%、约0.3%、约0.4%、约0.5%、约1%、约1.5%、约2%、约2.5%、约3%、约3.5%、约4%、约4.5%、约5%、约5.5%、约6%、约6.5%、约7%、约7.5%、约8%、约8.5%、约9%、约9.5%、约10%、约10.5%、约11%、约11.5%、约12%、约12.5%、约13%、约13.5%、约14%、约14.5%、约15%、约15.5%、约16%、约16.5%、约17%、约17.5%、约18%、约18.5%、约19%、约19.5%或约20%的至少一种细胞壁相关蛋白。
在一些实施方案中,该组合物可包含约0.1重量%至约20重量%的至少一种DNA或蛋白合成相关蛋白、约0.2重量%至约17重量%的至少一种DNA或蛋白合成相关蛋白、约0.3重量%至约15重量%的至少一种DNA或蛋白合成相关蛋白、约0.4重量%至约13重量%的至少一种DNA或蛋白合成相关蛋白、约0.5重量%至约10重量%的至少一种DNA或蛋白合成相关蛋白、约1重量%至约9.5重量%的至少一种DNA或蛋白合成相关蛋白、约1.5重量%至约9重量%的至少一种DNA或蛋白合成相关蛋白、约1.5重量%至约8.5重量%的至少一种DNA或蛋白合成相关蛋白、约1.5重量%至约8重量%的至少一种DNA或蛋白合成相关蛋白、约2重量%至约7.5重量%的至少一种DNA或蛋白合成相关蛋白、约2.5重量%至约7重量%的至少一种DNA或蛋白合成相关蛋白、约3重量%至约6.5重量%的至少一种DNA或蛋白合成相关蛋白、约3.5重量%至约6重量%的至少一种DNA或蛋白合成相关蛋白、或约4重量%至约5.5重量%的至少一种DNA或蛋白合成相关蛋白。在一些实施方案中,该组合物可包含按重量计约0.1%、约0.2%、约0.3%、约0.4%、约0.5%、约1%、约1.5%、约2%、约2.5%、约3%、约3.5%、约4%、约4.5%、约5%、约5.5%、约6%、约6.5%、约7%、约7.5%、约8%、约8.5%、约9%、约9.5%、约10%、约10.5%、约11%、约11.5%、约12%、约12.5%、约13%、约13.5%、约14%、约14.5%、约15%、约15.5%、约16%、约16.5%、约17%、约17.5%、约18%、约18.5%、约19%、约19.5%或约20%的至少一种DNA或蛋白合成相关蛋白。
在一些实施方案中,该组合物可包含约0.5重量%至约35重量%、约1重量%至约30重量%的至少一种代谢酶、约5重量%至约25重量%的至少一种代谢酶、约10重量%至约20重量%的至少一种代谢酶、约12重量%至约18重量%的至少一种代谢酶或约14重量%或16重量%的至少一种代谢酶。在一些实施方案中,该组合物可包含按重量计约0.5%、约1%、约2%、约3%、约4%、约5%、约6%、约7%、约8%、约9%、约10%、约11%、约12%、约13%、约14%、约15%、约16%、约17%、约18%、约19%、约20%、约21%、约22%、约23%、约24%、约25%、约26%、约27%、约28%、约29%、约30%、约31%、约32%、约33%、约34%或约35%的至少一种代谢酶。
在一些实施方案中,护肤组合物还可包含至少一种润肤剂。在一些实施方案中,该组合物可包含约0.5重量%至约50重量%的至少一种润肤剂、约5重量%至约45重量%的至少一种润肤剂、约10重量%至约40重量%的至少一种润肤剂、约15重量%至约35重量%的至少一种润肤剂或约20重量%至约30重量%的至少一种润肤剂。在一些实施方案中,该组合物可包含按重量计约0.5%、约5%、约10%、约15%、约20%、约25%、约30%、约35%、约40%、约45%或约50%的至少一种润肤剂。
在一些实施方案中,该至少一种润肤剂可以是植物油或动物油或脂肪,诸如大麻籽油、星果棕(Astrocaryum yauaperyense fat)脂肪、芸苔(Brassica campestris)籽油、非洲芒果核油、杏(Prunus armeniaca)核油、亚麻荠(Camelina)籽油、刺阿甘树(Arganiaspinosa)核油、杏核油、沙棘(Hippophae rhamnoides)油、车前叶蓝蓟(Echiumplantagineum)籽油、鸸鹋油、橘棘鲷(orange roughy)油、芥花油、日本榧树(Torreanucifera)籽油、印度藤黄(Garcinia indica Choisy)籽油、葛缕子(Carum carvi)籽油、杏(Prunus armeniaca L.var anus Maxim)油、石栗(Aleurites moluccana)油、含有芥酸的海甘蓝(Crambe abyssinica)籽油、蔓越莓(Vaccinium macrocarpon)籽油、核桃籽油、黑加仑(Ribes nigrum)籽油、越橘(Vaccinium vitis-idaea L.)籽油、稻米胚芽油、日本五针松(Pinus parviflora)籽油、山茶花(Camellia sasanqua)油、娑罗(Shorea)籽油、氧化玉米油、乳木果油和脂肪、狭翅娑罗(Shorea stenoptera)(籽)乳脂、白羽扇豆(Lupinus albus)籽油、氢化牛油果油、氢化橄榄油、氢化牛脂、氢化大豆油、氢化荷荷巴油、氢化植物油、氢化棕榈仁油、氢化棕榈油、氢化蓖麻油、氢化荷荷巴油、氢化植物油、氢化椰子油、伯尔硬胡桃(Sclerocarya birrea)籽油、非洲鸵鸟(Struthio camelus)油、西番莲(Passifloraeincarnata L.)籽油、茶树(Camellia sinensis)油、山茶油、红莓苔子(Vacciniumoxycoccos)籽油、大花可可树(Theobroma grandiflorum)籽脂肪、猪油、奶油、薏米(Coixlachryma-jobi L.var.ma-yuen Stapf Coix)油、巴巴苏油、花生油、开心果(Pistachio)籽油、沙棘(Hippophae rhamnoides)油、葵花籽油、黑果越桔(Vaccinium myrtillus L.)籽油、葡萄籽油、部分氢化紫苏油、部分氢化马油、西梅籽油、花椰菜籽油、丝瓜(Luffacylindrica)籽油、美洲南瓜(Cucurbita pepo Linnaeus)籽油、雨生红球藻(Haematococcus pluvialis)油、悬钩子(Rubus chamaemorus)籽油、松籽油、印度芒果(Mangifera indica)籽油、印度芒果籽油、水貂油、印度楝(Melia azadirachta)籽油、桃仁油、begetable油、油茶树(Camellia oleifera)油、覆盆子(Rubus idaeus)籽油、苹果籽油、琉璃苣(Borago officinalis)籽油、玫瑰果油、辣木(Moringa oleifera Lam.)籽油、全缘叶澳洲坚果(Macadamia integrifolia)油、蓖麻油、橄榄油、杏仁油、可可油、山茶油、椰子油、棕榈油、牛脂、荷荷巴油、葡萄籽油、鳄梨油、红花油、芝麻油、茶树油、月见草油、小麦胚芽油、榛子油、白池花(Limnanthes alba)油、桃(Prumus persica)仁油、薄荷油、互叶白千层(Melaleuca alternifolia)油、玉米油、菜籽油、葵花籽油、亚麻籽油、棉油、大豆油、花生油、米糠油、可可油、乳木果油、茴香油、紫苏油、洋甘菊油、胡萝卜油、黄瓜油、蛋黄油、牛肉脂肪、马脂肪、鱼油、龟油、橘棘鲷油或它们的组合。
在一些实施方案中,该至少一种润肤剂可以是蜡,诸如漆树果皮蜡、素方花(Jasminum officinale)蜡、橙果皮蜡、橙花蜡、氢化荷荷巴油酯、巴西棕榈蜡、小烛树蜡、红口水仙花(Narcissus poeticus L.)蜡、米糠蜡、白杨梅(Myrica rubra f.alba)果蜡、金合欢(sweet acacia)花蜡、晚香玉(Polianthes tuberosa)花蜡、蜂蜡、鲸蜡、橘棘鲷油、羊毛脂、米蜡、褐煤蜡、地蜡(ozokerite)或它们的组合。
在一些实施方案中,该至少一种润肤剂可以是烃,诸如异二十烷、异十二烷、异十六烷、二乙基己基环己烷、五氢角鲨烷、矿物油、矿脂、聚异丁烯、氢化聚异丁烯、聚丁烯、角鲨烷、角鲨烯、微晶蜡、地蜡(ceresin wax)、石蜡、凡士林、地蜡(ozokerite)、α-烯烃低聚物、十四烯或它们的组合。
在一些实施方案中,润肤剂可以是天然或合成的脂肪酸,诸如异构化的亚油酸、牛脂、脂肪酸(C14-28)、脂肪酸(C20-40)、氢化椰子油脂肪酸、棕榈仁脂肪酸、10-羟基癸酸、支链脂肪酸(C14-28)、支链脂肪酸(C21-31)、山萮酸、癸酸、肉豆蔻酸、棕榈酸、硬脂酸、山萮酸、羊毛脂脂肪酸、亚油酸、亚麻酸、月桂酸、油酸、异硬脂酸、十一碳烯酸、1,2-羟基硬脂酸、棕榈油酸、芥酸、二十二碳六烯酸、二十碳五烯酸、异十六碳烯酸酸、反异二十一碳酸、异壬酸、2-乙基己酸或它们的组合。
在一些实施方案中,该至少一种润肤剂可以是天然或合成的高级醇,诸如C12-16醇、C14-22醇、C20-22醇、C20-40醇、C30-50醇、芸苔属油菜籽甾醇、异鲸蜡醇、异丙醇、辛二醇、米糠甾醇、氢化油菜籽醇、鲸醇、硬脂醇、己基癸醇、辛基十二烷醇、月桂醇、辛醇、肉豆蔻醇、油醇、鲸蜡硬脂醇、花生醇、山萮醇、荷荷巴醇、鲛肝醇、鲨油醇、鲨肝醇、异硬脂醇、鲸蜡醇、胆固醇、植物甾醇、羊毛脂醇、氢化羊毛脂醇、棕榈醇、2-癸基十四醇或它们的组合。
在一些实施方案中,该至少一种润肤剂可以是酯,诸如C12-15-链烷醇聚醚-9羧酸异丙酯、辛基十二烷基吡咯烷酮羧酸、薄荷基吡咯烷酮羧酸、月桂基吡咯烷酮羧酸、PEG-2isosedes-7羧酸鲸蜡酯、二-PPG-3肉豆蔻醚己二酸酯、二-PPG-2肉豆蔻醇聚醚-10己二酸酯、己二酸二异丙酯、己二酸二庚基十一烷基酯、鳄梨油酸乙酯、鳄梨油酸丁酯、葡糖醇聚醚-20苯甲酸甲酯、异硬脂酸乙酯、(异硬脂酸/琥珀酸)蓖麻油、氢化蓖麻油异硬脂酸酯、鲨肝醇异硬脂酸酯、己基癸醇异硬脂酸酯、(异硬脂酸/蜂蜡/琥珀酸)蓖麻油、异壬酸异癸酯、异壬酸异十三烷基酯、异壬酸异壬酯、异壬酸辛酯、异壬酸鲸蜡酯、乙酸异丁酸蔗糖酯、二十碳烯酸辛酰酯、乙基己酸丁乙基丙二醇酯、辛基十二醇芥酸酯、油醇芥酸酯、烷醇辛酸酯(C14、C16和C18)、(辛酸/硬脂酸/己二酸)甘油酯、辛酸十六烷基、辛酸硬脂酸酯、鲸蜡硬脂醇乙基己酸酯、己基癸醇乙基己酸酯、油酸乙酯、油醇油酸酯、辛酸/癸酸甘油酯、辛酸/癸酸/椰子脂肪酸甘油酯、辛酸/癸酸/琥珀酸甘油三酯、癸酸鲸蜡酯、柠檬酸三异辛酯、柠檬酸三(辛基十二烷醇)酯、柠檬酸/乳酸/亚油酸/油酸四甘油酯、异硬脂醇二聚甘油琥珀酸酯、琥珀酸二乙氧基乙酯、琥珀酸二辛酯、植物甾醇米糠油脂肪酸、乙酸鲸蜡酯、乙酸法呢醇酯、乙酸羊毛脂醇酯、乙酸芳樟醇、二异硬脂酸丙二醇酯、二聚亚油醇二异硬脂酸酯、二聚亚油醇二异硬脂酸酯、新戊二醇二异硬脂酸酯、新戊二醇二乙基己酸酯、PEG-18蓖麻油二油酸酯、二-(辛酸/癸酸)丁二醇、异山梨醇二辛酸酯、二-(辛酸/癸酸)聚乙二醇、二椰油酰基季戊四醇二硬脂醇柠檬酸酯、聚乙二醇二硬脂酸酯、PG-20甲基葡糖二硬脂酸酯、季戊四醇二硬脂酸酯、戊二醇二新戊酸二乙酯、戊二醇二新戊酸甲酯、聚乙二醇二壬酸酯、C10-30胆固醇/羊毛甾醇酯、C12至C18十六烷基酯、乙二醇二月桂酸酯、二聚亚油酸二异丙酯、氢化松香酸季戊四醇酯、氢化松香酸甲酯、二异硬脂酸甘油酯/氢化松香酸酯、硬脂酸乙基己酯、异鲸蜡醇硬脂酰氧基硬脂酸酯、辛基十二烷基硬脂酰氧基硬脂酸酯、癸二酸二丁基辛酯、辛基十二烷基/PPG-3肉豆醇醚二聚亚油酸酯、二-(异硬脂醇/植物甾醇)二聚亚油酸酯、二鲸蜡硬脂醇二聚亚油酸酯、氢化蓖麻油二聚亚油酸酯、硬脂酰/PPG-3肉豆蔻醚二聚亚油酸酯、二聚亚油醇二聚亚油酸酯、双-山嵛醇/异硬脂醇/植物甾醇二聚亚油醇二聚亚油酸酯、植物甾醇/异硬脂醇/鲸蜡醇/硬脂醇/山嵛醇二聚亚油酸酯、二聚亚油醇氢化松香凝聚物、C14-15碳酸二烷基酯、碳酸二乙基己酯、碳酸二辛酯、季戊四醇四异硬脂酸酯、季戊四醇四辛酸酯、聚甘油-10十二-辛酸酯/癸酸酯、二异鲸蜡醇十二碳二酸酯、二辛基十二醇十二碳二酸酯、三异硬脂酸酯、赤藓醇三(乙基己酸)酯、二(三羟甲基)丙烷三乙基己酸酯、甘油三(乙基己酸)酯(三异辛酸甘油酯)、三羟甲基丙烷三乙基己基己酸酯、三辛精、辛酸/癸酸甘油三酯、辛酸/癸酸/硬脂酸甘油三酯、辛酸/癸酸/肉豆蔻酸/硬脂酸甘油三酯、C8-12酸甘油三酯、三硬脂精、三棕榈精、三棕榈油精、三羟基硬脂精、三山嵛酸酯、二聚季戊四醇三-聚羟基硬脂酸酯、三肉豆蔻精、乳酸C12-15烷基酯、乳酸乙酯、乳酸辛基十二烷基酯、乳酸丁酯、乳酸薄荷酯、新戊酸异癸酯、新戊酸肉豆蔻酯、壬酸辛酯、壬酸胆固醇酯、棕榈酸乙基己酯、棕榈酸十六烷基酯、双-二甘油多酰基己二酸酯-1、双-二甘油多酰基己二酸酯-2、二聚季戊四醇五羟基硬脂酸酯/五异硬脂酸酯、乙基己基二羟基硬脂酸酯、羟基硬脂酸辛酯、氢化蓖麻油羟基硬脂酸酯、二季戊四醇六羟基硬脂酸酯/硬脂酸酯/松香酸酯、植物甾醇羟基硬脂酸酯、PPG-6蓖麻油酸酯、蓖麻油酸甲酯、丙酸肉豆蔻基酯、C10-40异烷基酸胆固醇酯、二季戊四醇六羟基硬脂酸酯、二季戊四醇六羟基硬脂酸酯/六硬脂酸酯/六松脂酸酯、硬脂醇庚酸酯、甘油山嵛酸酯/二十酸酯、荷荷巴酯、荷荷巴异丙酯、澳洲坚果油酸乙酯、胆甾醇澳洲坚果油酸酯、植物甾醇澳洲坚果油酸酯、马来酸二辛酯、亚丁香基丙二酸二乙基己酯、肉豆醇甲基氨基丙酸己基癸基酯、甲基巴豆酸香茅酯、白池花低聚交酯、辛基十二醇白池花籽油酸酯、甘油椰油酸酯/柠檬酸酯/乳酸酯、椰油酸癸酯、胆甾醇丁酸酯、二氢胆甾醇丁酸酯、辛基十二醇羊毛脂酸酯、胆甾醇羊毛脂酸酯、辛基十二醇蓖麻醇酸酯、苹果酸二乙基己酯、三油醇磷酸酯、三鲸蜡醇磷酸酯、三-2-乙基己酸甘油酯、2-乙基己酸鲸蜡酯、二-2-乙基己酸新戊二醇酯、肉豆蔻酸异丙酯、肉豆蔻酸丁酯、棕榈酸异丙酯、硬脂酸乙酯、棕榈酸辛酯、异鲸蜡醇异硬脂酸酯、硬脂酸丁酯、亚油酸乙酯、亚油酸异丙酯、油酸乙酯、异鲸蜡醇肉豆蔻酸酯、异硬脂醇肉豆蔻酸酯、异硬脂醇棕榈酸酯、辛基十二醇肉豆蔻酸酯、癸二酸二乙酯、己二酸二异丙酯、新戊酸异烷基酯、辛酸/癸酸甘油三酯、三羟甲基丙烷三-2-乙基己酸酯、三羟甲基丙烷三异硬脂酸酯、季戊四醇四-2-乙基己酸酯、鲸蜡醇辛酸酯、月桂酸癸酯、月桂酸己酯、肉豆蔻酸癸酯、肉豆蔻醇肉豆蔻酸酯、鲸蜡醇肉豆蔻酸酯、三肉豆蔻酸甘油酯、硬脂醇硬脂酸酯、油酸癸酯、鲸蜡醇蓖麻油酸酯、异硬脂醇月桂酸酯、异十三醇肉豆蔻酸酯、异鲸蜡醇棕榈酸酯、硬脂酸辛酯、异鲸蜡醇硬脂酸酯、油酸异癸酯、辛基十二醇油酸酯、辛基十二醇亚油酸酯、异硬脂酸异丙酯、鲸蜡硬脂醇2-乙基己酸酯、硬脂醇2-乙基己酸酯、异硬脂酸己酯、乙二醇二辛酸酯、乙二醇二油酸酯、丙二醇二油酸酯、丙二醇二癸酸酯、丙二醇二辛酸酯/二癸酸酯、辛酸/癸酸甘油三酯、丙二醇二辛酸酯、新戊二醇二癸酸酯、新戊二醇二辛酸酯、三辛酸甘油酯、三(十一烷)酸甘油酯、三异棕榈酸甘油酯、三异硬脂酸甘油酯、辛基十二醇新癸酸酯、辛基十二醇新戊酸酯、异硬脂醇辛酸酯、己基癸醇新癸烷、己基癸醇新癸酸酯、辛基十二醇新癸酸酯、异硬脂醇异硬脂酸酯、辛基十二醇异硬脂酸酯、聚油酸甘油酯、聚甘油异硬脂酸酯、碳酸二丙酯、碳酸C12至C18二烷基酯、柠檬酸三异鲸蜡酯、柠檬酸三异花生酯、柠檬酸三异辛酯、月桂醇乳酸酯、肉豆蔻醇乳酸酯、鲸蜡醇乳酸酯、辛基十二烷基乳酸酯、羊毛脂乳酸酯、柠檬酸三乙酯、乙酰柠檬酸三乙酯、乙酰柠檬酸三丁酯、柠檬酸三辛酯、二异硬脂醇苹果酸酯、2-乙基己基羟基硬脂酸酯、2-乙基己基琥珀酸酯、己二酸二异丁酯、癸二酸二异丙酯、癸二酸二异辛酯、胆甾醇硬脂酸酯、胆甾醇异硬脂酸酯、胆甾醇羟基硬脂酸酯、胆甾醇油酸酯、二氢胆甾醇油酸酯、植物甾醇异硬脂酸酯、植物甾醇油酸酯、12-硬脂酰羟基硬脂酸异辛酯、12-硬脂酰羟基硬脂酸硬脂醇酯、12-硬脂酰羟基硬脂酸异硬脂醇酯、己基癸醇二甲基辛酸酯和羊毛脂酸异丙酯;羊毛脂类,诸如液体羊毛脂、氢化羊毛脂、吸附精制羊毛脂、乙酸羊毛脂、乙酰化羊毛脂、羟基羊毛脂、聚氧乙烯羊毛脂、硬羊毛脂脂肪酸和鲸蜡羊毛脂醇乙酸酯;鞘磷脂类,诸如卵磷脂、磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰甘油、磷脂酰肌醇、鞘髓磷脂或它们的组合。
在一些实施方案中,该至少一种润肤剂可以是磷脂,诸如磷脂酸和溶血卵磷脂;磷脂衍生物,诸如氢化大豆磷脂、部分氢化大豆磷脂、氢化蛋黄磷脂和部分氢化蛋黄磷脂;固醇类,诸如二氢胆固醇、羊毛固醇、二氢羊毛固醇和胆酸;含硅油剂,诸如甲基苯基聚硅氧烷、甲基氢聚硅氧烷、八甲基环四硅氧烷、硬脂氧基硅酮、十甲基环五硅氧烷或十二甲基环六硅氧烷;皂苷配基类;皂苷类;和含氟油剂,诸如全氟聚醚、全氟萘烷、全氟辛烷或它们的组合。
在一些实施方案中,该至少一种润肤剂可以是椰油甘油酯、鲸蜡醇、十四烷、红花(红花)油质体或它们的组合。
在一些实施方案中,该组合物还可包含至少一种乳化剂。在一些实施方案中,该组合物可包含约1重量%至约15重量%的至少一种乳化剂、约2重量%至约10重量%的至少一种乳化剂、约3重量%至约9重量%的至少一种乳化剂、约4重量%至约8重量%的至少一种乳化剂或约5重量%至约7重量%的至少一种乳化剂。在一些实施方案中,该组合物可以包含按重量计约1%、约2%、约3%、约4%、约5%、约6%、约7%、约8%、约9%、约10%、约11%、约12%、约13%、约14%或约15%的至少一种乳化剂。
在一些实施方案中,该至少一种乳化剂可以是阳离子乳化剂、阴离子乳化剂或非离子乳化剂。在一些实施方案中,该至少一种乳化剂可以是甘油硬脂酸酯、甘油单油酸酯、PEG硬脂酸酯(诸如但不限于PEG-100硬脂酸酯、PEG-200硬脂酸酯、PEG-300硬脂酸酯等)、山梨坦倍半油酸酯、山梨坦橄榄油酸酯、山梨坦硬脂酸酯、卵磷脂、十一烷醇聚醚-3、PEG-20甲基葡糖倍半硬脂酸酯、十三烷醇聚醚-3、十三烷醇聚醚-12、月桂醇聚醚-9、山嵛酰氧基硬脂酸、油醇聚醚-2、油醇聚醚-20、山梨坦月桂酸酯、山梨坦棕榈酸酯、山梨坦油酸酯、山梨坦三油酸酯、硬脂醇聚醚-2、硬脂醇聚醚-20、硬脂醇聚醚-21、月桂醇聚醚-23、C11-15-链烷醇聚醚-15、PPG-24-丁醇聚醚-27、Avena sativa(燕麦)肽、环氧乙烷和环氧丙烷的高分子量聚合物、PPG5-鲸蜡醇聚醚-10磷酸酯、油醇聚醚-5磷酸酯、二油醇磷酸酯、油醇聚醚-3磷酸酯、油醇聚醚-10磷酸酯、月桂醇磷酸酯、十三烷醇聚醚-3磷酸酯、十三烷醇聚醚-6磷酸酯、癸醇聚醚-6磷酸酯、三月桂醇聚醚-4磷酸酯、C20-22醇、聚甘油-10十油酸酯、聚甘油-3油酸酯、PEG/PPG-20/6聚二甲基硅氧烷、双PEG/PPG-20/20聚二甲基硅氧烷、双PEG/PPG-16/16PEG/PPG-16/16聚二甲基硅氧烷、双PEG/PPG20/5PEG/PPG-20/5聚二甲基硅氧烷、甲氧基PEG/PPG-25/4聚二甲基硅氧烷、双PEG/PPG-14/14聚二甲基硅氧烷、PEG-11甲醚聚二甲基硅氧烷、PEG/PPG-20/22丁基醚聚二甲基硅氧烷、月桂基PEG-9聚二甲基硅氧乙基聚二甲基硅氧烷、PEG-10聚二甲基硅氧烷、聚甘油-3二硅氧烷聚二甲基硅氧烷、月桂基聚甘油-3聚二甲基硅氧乙基聚二甲基硅氧烷、月桂基PEG-8聚二甲基硅氧烷、硬脂酸钠、蔗糖月桂酸酯、蔗糖肉豆蔻酸酯、蔗糖硬脂酸酯、甲基葡糖倍半硬脂酸酯或它们的组合。
在一些实施方案中,该至少一种乳化剂可以是黄原胶、阿拉伯树胶、小烛树聚甘油-3酯、荷荷巴聚甘油-3酯、米糠聚甘油-3酯、硬脂酸甘油酯、鲸蜡硬脂醇、硬脂酰乳酸钠或它们的组合。
在一些实施方案中,该组合物还可包含约0.1重量%至约10重量%的至少一种抗氧化剂、约0.1重量%至约9重量%的至少一种抗氧化剂、约0.5重量%至约8.5重量%的至少一种抗氧化剂、约1重量%至约7.5重量%的至少一种抗氧化剂、约1.5重量%至约7重量%的至少一种抗氧化剂、约2重量%至约6.5重量%的至少一种抗氧化剂、约2.5重量%至约6重量%的至少一种抗氧化剂、约3重量%至约5.5重量%的至少一种抗氧化剂或约3.5重量%至约5重量%的至少一种抗氧化剂。在一些实施方案中,该护肤组合物可包含约0.1%、约0.5%、约1%、约1.5%、约2%、约2.5%、约3%、约3.5%、约4%、约4.5%、约5%、约5.5%、约6%、约6.5%、约7%、约7.5%、约8%、约8.5%、约9%、约9.5%或约10%的至少一种抗氧化剂。
在一些实施方案中,该至少一种抗氧化剂可以是维生素A及其衍生物和盐,诸如视黄醇、脱氢视黄醇、视黄醇乙酸酯、视黄醇棕榈酸酯、视黄醛、视黄酸和维生素A油;维生素B及其衍生物和盐,诸如吡哆醇、吡哆醛、吡哆醛-5-磷酸和吡哆胺;维生素D及其衍生物和盐,诸如麦角钙化醇、胆钙化醇和1,2,5-二羟基胆钙化醇;或维生素E及其衍生物和盐,诸如α-生育酚、β-生育酚、γ-生育酚、δ-生育酚、α-生育三烯酚、β-生育三烯酚、γ-生育三烯酚、δ-生育三烯酚、生育酚乙酸酯和生育酚烟酸酯;或它们的组合。在一些实施方案中,该至少一种抗氧化剂可以是奎诺(trolox)及其盐。
在一些实施方案中,该至少一种抗氧化剂可以是类胡萝卜素及其衍生物,诸如α-胡萝卜素、β-胡萝卜素、γ-胡萝卜素、隐黄素、虾青素、岩藻黄素或它们的组合。
在一些实施方案中,该至少一种抗氧化剂可以是二羟基甲苯、丁羟甲苯、丁羟苯甲醚、二丁羟甲苯、α-硫辛酸、脱氢硫辛酸、谷胱甘肽以及它们的衍生物和盐;尿酸;赤藻糖酸及其衍生物和盐,诸如赤藻糖酸和赤藻糖酸钠;没食子酸及其衍生物和盐,诸如没食子酸和没食子酸丙酯;芸香苷及其衍生物和盐,诸如芸香苷和α-糖基芸香苷;色氨酸及其衍生物和盐;组氨酸及其衍生物和盐;半胱氨酸及其衍生物和盐,诸如N-乙酰半胱氨酸、N-乙酰高半胱氨酸、N-辛酰基半胱氨酸和N-乙酰半胱氨酸甲酯;胱氨酸及其衍生物和盐,诸如N,N'-二乙酰基胱氨酸二甲酯、N,N'-二辛酰基胱氨酸二甲酯和N,N'-二辛酰基高胱氨酸二甲酯;肌肽及其衍生物和盐;高肌肽及其衍生物和盐;鹅肌肽及其衍生物和盐;脱羧肌肽及其衍生物和盐;含有组氨酸和/或色氨酸和/或组胺的二肽或三肽衍生物及其盐;类黄酮,诸如黄烷酮、黄酮、花色苷、花色素、黄酮醇、槲皮素、槲皮苷、杨梅酮、非瑟酮、金缕梅单宁、儿茶素、表儿茶素、没食子儿茶素、表没食子儿茶素、表儿茶素没食子酸酯和表没食子儿茶素没食子酸酯;单宁酸、咖啡酸、阿魏酸、原儿茶酸、查耳酮、谷维素(orizanol)、鼠尾草酚(carnosol)、芝麻酚、芝麻素、芝麻酚林、姜酮、姜黄素、四氢姜黄素、丁子香酰胺(clovamide)(咖啡酰多巴(caffeoyldopa))、脱氧丁子香酰胺、姜烯酚、辣椒素、香草酰胺、鞣花酸、溴酚、灰绿曲霉黄色素(flavoglaucin)、类黑精、核黄素、核黄素丁酸酯、核黄素单核苷酸、黄素腺嘌呤二核苷酸、泛醌、泛醇、甘露糖醇、胆红素、胆固醇、依布硒啉(ebselen)、硒代甲硫氨酸、血浆铜蓝蛋白、转铁蛋白、乳铁蛋白、白蛋白、超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、金属硫蛋白、硫氧还蛋白、硫代牛磺酸、O-膦酰基吡哆罗丹明和N-(2-羟基苄基)氨基酸以及它们的衍生物和盐;N-(4-吡啶氧基亚甲基)氨基酸及其衍生物和盐;以及其他,诸如赖氨酸、1-甲硫氨酸、脯氨酸、水飞蓟素、茶提取物、葡萄皮/葡萄籽提取物、黑色素、迷迭香提取物或它们的组合。
在一些实施方案中,该至少一种抗氧化剂可以是维生素E、维生素A、维生素B或维生素D。
在一些实施方案中,该组合物还可包含约0.1重量%至约10重量%的至少一种保湿剂、约0.5重量%至约10重量%的至少一种保湿剂、约0.5重量%至约9重量%的至少一种保湿剂、约0.5重量%至约8重量%的至少一种保湿剂、约0.5重量%至约7重量%的至少一种保湿剂、约0.5重量%至约6重量%的至少一种保湿剂、0.5重量%至约5重量%的至少一种保湿剂、约1重量%至约10重量%的至少一种保湿剂、约2重量%至约9重量%的至少一种保湿剂、约3重量%至约8重量%的至少一种保湿剂、约4重量%至约7重量%的至少一种保湿剂或约5重量%至约6重量%的至少一种保湿剂。在一些实施方案中,该组合物可包含按重量计约0.1%、约0.5%、约1%、约1.5%、约2%、约2.5%、约3%、约3.5%、约4%、约4.5%、约5%、约5.5%、约6%、约6.5%、约7%、约7.5%、约8%、约8.5%、约9%、约9.5%或约10%的至少一种保湿剂。
在一些实施方案中,该至少一种保湿剂可以是甘油、山梨醇、亚烷基二醇(例如,丙二醇、二丙二醇、聚丙二醇、聚乙二醇、己二醇、丁二醇、1,3-丁二醇等)、丙二醇、辛二醇、乙基己基甘油、C1-3烷氧基化葡萄糖衍生物、三乙酸甘油酯、己三醇、乙烯醇、木糖醇、麦芽糖醇、聚葡萄糖、烷氧基化甘油(例如,乙氧基化甘油)、皂树皮、尿素、芦荟凝胶、MP Diol(也称为2-甲基-1,3-丙二醇)、α羟酸(例如,乳酸)、蜂蜜或它们的组合。
在一些实施方案中,该至少一种保湿剂可以是丙二醇、辛二醇、乙基己基甘油或它们的组合。
螯合剂与金属离子结合并防止它们与调配物中的其他物质发生化学反应。在一些实施方案中,该护肤组合物还可包含约0.1重量%至约5重量%的至少一种螯合剂、约0.5重量%至约4重量%的至少一种螯合剂、约0.5重量%至约3重量%的至少一种螯合剂、约0.5重量%至约2.5重量%的至少一种螯合剂、约1重量%至约5重量%的至少一种螯合剂、约1.5重量%至约3.5重量%的至少一种螯合剂或约2重量%至约3重量%的至少一种螯合剂。在一些实施方案中,该护肤组合物可包含按重量计约0.1%、约0.5%、约1%、约1.5%、约2%、约2.5%、约3%、约3.5%、约4%、约4.5%或约5%的至少一种螯合剂。
在一些实施方案中,该至少一种螯合剂可以是乙二胺四乙酸盐,诸如乙二胺四乙酸盐(EDTA)、EDTA二钠盐、EDTA三钠盐和EDTA四钠盐,羟乙基乙二胺三乙酸盐,诸如羟乙基乙二胺三乙酸钠盐;乙二胺二琥珀酸三钠;磷酸及其钠盐等,诸如三聚磷酸、二亚乙基三胺五乙酸盐、植酸和依替膦酸;聚(氨基酸)类,诸如草酸钠、聚天冬氨酸和聚谷氨酸;以及其他,诸如聚磷酸钠、偏磷酸钠、磷酸、焦磷酸盐、六偏磷酸盐、植酸钠、柠檬酸钠、柠檬酸、丙氨酸、二羟基乙基甘氨酸、葡糖酸、琥珀酸、酒石酸或它们的组合。
在一些实施方案中,该至少一种螯合剂可以是乙二胺二琥珀酸三钠、植酸钠或它们的组合。
在一些实施方案中,该组合物还可包含约0.5重量%至约10重量%的至少一种增白剂、约1重量%至约10重量%的至少一种增白剂、约2重量%至约9重量%的至少一种增白剂、约3重量%至约8重量%的至少一种增白剂、约4重量%至约7重量%的至少一种增白剂、约5重量%至约6重量%的至少一种增白剂。在一些实施方案中,该护肤组合物可包含约2重量%至约5重量%的至少一种增白剂。在一些实施方案中,该护肤组合物可包含按重量计约0.1%、约0.5%、约1%、约1.5%、约2%、约2.5%、约3%、约3.5%、约4%、约4.5%、约5%、约5.5%、约6%、约6.5%、约7%、约7.5%、约8%、约8.5%、约9%、约9.5%或约10%的至少一种增白剂。
在一些实施方案中,该至少一种增白剂可以是烷氧基水杨酸及其盐,诸如3-甲氧基水杨酸、3-乙氧基水杨酸、4-甲氧基水杨酸、4-乙氧基水杨酸、4-丙氧基水杨酸、4-异丙氧基水杨酸、4-丁氧基水杨酸、5-甲氧基水杨酸、5-乙氧基水杨酸、5-丙氧基水杨酸或它们的组合。
在一些实施方案中,该至少一种增白剂可以是氢醌及其衍生物,诸如熊果苷、α-熊果苷、氢醌α-L-葡萄糖、氢醌β-L-葡萄糖、氢醌α-D-半乳糖、氢醌β-D-半乳糖、氢醌α-L-半乳糖、氢醌β-L-半乳糖、氢醌α-D-核糖、氢醌β-D-核糖、氢醌α-L-核糖、氢醌β-L-核糖、氢醌α-D-阿拉伯糖、氢醌β-D-阿拉伯糖、氢醌α-L-阿拉伯糖、氢醌β-L-阿拉伯糖、氢醌α-D-葡糖胺、氢醌β-D-葡糖胺、氢醌α-L-葡糖胺、氢醌β-L-葡糖胺、氢醌α-D-半乳糖胺、氢醌β-D-半乳糖胺、氢醌α-L-半乳糖胺、氢醌β-L-半乳糖胺、氢醌α-D-葡糖醛酸、氢醌β-D-葡糖醛酸、氢醌α-L-葡糖醛酸、氢醌β-L-葡糖醛酸、氢醌α-D-半乳糖醛酸、氢醌β-D-半乳糖醛酸、氢醌α-L-半乳糖醛酸、氢醌β-L-半乳糖醛酸或它们的组合。
在一些实施方案中,该至少一种增白剂可以是传明酸(ranexamic acid)及其衍生物和盐;雷琐辛(resorcin)及其衍生物,诸如4-正丁基间苯二酚;曲酸及其衍生物和盐;鞣花酸和亚油酸及其盐、苯汞六氯酚、氧化汞、氯化汞、过氧化氢、过氧化锌、2-氨基苯酚及其衍生物、阿魏酸及其衍生物、胎盘提取物、谷胱甘肽、谷维素、丁基间苯二酚或它们的组合。
在一些实施方案中,该至少一种增白剂可以来自植物提取物,诸如茴芹(Pimpinella anisum)提取物、日本虎杖(Japanese knotweed)提取物、(Daphnepseudomezereum)提取物、Senna obtusifolia)提取物、决明子(Cassia obtusifolia L.)种子提取物、膜荚黄芪(Astsagalusu mambranaceus Bge)的根茎提取物、膜荚黄芪提取物、槭叶括楼(Trichosanthes laceribracteata)提取物、苍耳(Xanthium strumarium)提取物、天麻(Gastrodia elata)提取物、火棘(Pyracantha fortuneana)果实提取物、花虎杖(Polygonum sachalinense Fr.Schm)提取物、天台乌药(Lindera strychnifolia F.Vill)提取物、南瓜(Cucurbita)(南瓜)提取物、宽叶香蒲(Typha latifolia L.)提取物、甘遂(Euphorbia kansui Liou)提取物、龙牙草日本中井变种(Agrimonia pilosaLedeb.var.japonica(Miq.)Nakai)提取物、大叶钓樟(Lindera umbellata)提取物、虎耳草(Saxifraga fusca var.kikubuki)提取物、剑麻(Agave sisalana)提取物、威灵仙(Clematis chinensis)提取物、铁脚威灵仙(Clematis chinensis Osbeck)提取物、大岛樱(Cerasus speciosa(Koidz.)H.Ohba)提取物、大山樱(Cerasus sargentii(Rehder)H.Ohba)提取物、富士樱(Prunus incisa Thunb)提取物、高岭樱(Prunus nipponica)提取物、垂枝大叶早樱(Cerasus subhirtella(Miq.)S.Y.Sokolov)提取物、日本晚樱(Prunuslannesiana Wilson)提取物、紫菀(Aster tataricus)提取物、棕榈(Trachycarpusfortunei)提取物、鸢尾(Iris florentina L.)提取物、圆锥铁线莲(Clematisterniflora)提取物、柳叶木兰(Magnolia salicifolia)提取物、齿瓣虎耳草深裂变种(Saxifraga fortunei var.incisolobata)提取物、四翅月见草(Oenothera tetraptera)提取物、旋花科(Convolvulaceae)/菟丝子(Cuscuta chinensis Lam.)/金灯藤(C.Japonica Choisy)的干种提取物、南方菟丝子(Cuscuta australis)提取物、金灯藤(Cuscuta japonica Choisy)提取物、中亚苦蒿(Artemisia absinthium)提取物、高山蓍(Achillea alpina L.)提取物、白藓(Dictamnus albus)提取物、莳萝(Anethum graveolens L.)提取物、虎杖变种(Reynoutria japonica var.terminalis)提取物、刺蒺藜(Tribulus terrestris)提取物、石韦(Pyrrosia lingua(Thunb.)Farw)提取物、长苞香蒲(Typha domingensis)提取物、白芷(Angelica dahurica)根茎提取物、花卉布兰卡(floralblanca)提取物、hamula(Brickellia cabanillesy)提取物、滨艾(Artemisia fukudoMakino)提取物、田旋花(Convolvulus arvensis)提取物、檀香(Santalum album)提取物、亮盖灵芝(Ganoderma lucidum)提取物、益母草(Leonurus japonicus Houtt)提取物、银柳(Salix gilgiana Seemen)提取物、腺柳(Salix chaenomeloides Kimura)提取物、细柱柳(Salix gracilistyla)提取物、彩叶杞柳(Salix integra)提取物、杞柳(Salixkinuyanagi Kimura)提取物、尖叶紫柳(Salix koriyanagi Kimura)提取物、龙爪柳(Salixmatsudana Koidz.var.tortuosa Vilm)提取物、深山柳(Salix reinii Fr.et Sav)提取物、山柳(Salix sieboldiana)提取物、大叶柳(Toisusu urbaniana Kimura)提取物、蒿柳(Salix viminalis)/长柳(Salix longifolia)提取物、狐柳(Salix vulpina Anderss)提取物、辽杨(Populus maximowiczii A.Henry)提取物、杨梅(Myrica rubra)的干树皮提取物、美洲龙舌兰缘叶变种(Agave americana var.marginata)提取物、美洲龙舌兰(Agaveamericana)提取物、美洲龙舌兰缘叶变种(Agave americana var.marginata)提取物、结香(Edgeworthia papyrifera)紫草(Sieb.et Zucc)提取物、浒苔属(Enteromorpha)提取物、缘管浒苔(Enteromorpha linza)/扁浒苔(Enteromorpha compressa)提取物、海藻浒苔(Enteromorpha prolifera)提取物、扁浒苔(Enteromorpha compressa(Linnaeus)Nees)提取物、肠石莼(Ulva intestinalis Linnaeus)提取物、石莼(Ulva Linnaeus)提取物、海带(Laminaria)提取物、日本海带(Laminaria Japonica Areschoug)提取物、利尻海带(Laminaria ochotensis)提取物、皱海带(Laminaria religiosa Miyabe)提取物、狭叶海带(Laminaria angustata)提取物、羽状半裂裙带菜(Undaria pinnatifida)提取物、叶囊裙带菜(Undaria undarioides)提取物、青裙带菜(Undaria peterseniana)提取物、羊栖菜(Sargassum fusiforme)提取物、枯墨角藻(Fucus evanescens C.Agardh墨角藻(F.vesiculosus))提取物、树状团扇藻(Padina arborescens)提取物、南方团扇藻(Padinaaustralis Hauck)提取物、南方团扇藻变种(Padina australis Hauck var.cuneataTak.Tanaka et K.Nozawa)提取物、线细团扇藻(Padina boryana Thivy)提取物、大团扇藻(Padina crassa Yamada)提取物、日本团扇藻(Padina japonica Yamada)提取物、小团扇藻(Padina minor Yamada)提取物、有柄团扇藻(Padina stipitata Tak.Tanaka etK.Nozawa)提取物、锯齿麒麟菜(Eucheuma serra(J.Agardh)J.Agardh)提取物、对生麒麟菜(Eucheuma amakusaense Okamura)提取物、齿形麒麟菜(Eucheuma denticulatum(Burman)Collins et Hervey)提取物、珊瑚状麒麟菜(Eucheuma arnoldii Weber-van Bosse)提取物、红藻角叉菜(Chondrus ocelatus Holmes)提取物、异色角叉菜(Chondrus verrucosusMikami)提取物、巨角叉菜(Chondrus nipponicus Yendo)提取物、树枝角叉菜(Chondruspinnulatus(Harvey)Okamura)提取物、杉藻目(Gigartinales Schmitz)提取物、线形杉藻(Chondracanthus teedii)提取物、小杉藻(Chondracanthus intermedius)提取物、宽叶网翼藻(Dictyopteris latiuscula)提取物、(Dictyopteris polypodioides)提取物、草水云(Sphaerotrichia divaricata(C.Agardh)Kylin)提取物、Cymathaere提取物、Cymathaerejaponica提取物、半叶马尾藻(Sargassum hemiphyllum Agardh)提取物、重叠马尾藻(Sargassum segii)提取物、线形马尾藻(Sargassum filicinum)提取物、马尾藻(Sargassum sagamianum)提取物、马尾藻(Sargassum nigrifolium)提取物、球囊马尾藻(Sargassum piluliferum(Turner)C.Agardh)提取物、马尾藻(Sargassum tosaenseYendo)提取物、展枝马尾藻(Sargassum patens C.Agardh)提取物、鼠尾藻(Sargassumthunbergii(Mertens ex Roth)Kuntze)提取物、任氏马尾藻(Sargassum ringgoldianumHarvey ssp.Ringgoldianum)提取物、蜈蚣藻(Grateloupia filicina(Lamouroux)C.Agardh)提取物、阿氏海膜(Halymenia agardhii)提取物、多指粘滑藻(Sebdeniapolydactyla)提取物、顶状蜈蚣藻(Grateloupia acuminata Holmes)提取物、扇形海柏(Polyopes affinis(Harvey)Kawaguchi et Wang)提取物、江蓠(Gracilaria gagas)提取物、伴绵藻(Ceratodictyon spongiosum Zanardini)提取物、链状节荚藻(Lomentariacatenata Harvey)提取物、扁节荚藻(Lomentaria pinnata Segawa)提取物、扁节荚藻(Lomentaria pinnata Segawa)提取物、异枝凹顶藻(Laurencia intermedia Yamada)提取物、波状凹顶藻(Laurencia undulata)提取物、羽枝凹顶藻(Laurencia pinnata Yamada)提取物、红羽凹顶藻(Laurencia brongniartii J.Agardh)提取物、Odonthaliacorymbifera(Gmelin)Greville提取物、椴树(Tilia)提取物、Camotede azafran提取物、木槿属(Hibiscus)提取物、Poleoverde verde提取物、萝卜(Raphanus sativus)提取物、海蒿子(Sargassum confusum C.Agardh)提取物、海黍子(Sargassum kjellmanianum Yendo)提取物、大马尾藻(Sargassum macrocarpum C.Agardh)提取物、回回苏(Perilla frutescensvar.crispa)提取物、胎盘提取物、“RUSINOL”(4-正丁基间苯二酚)、蚕丝提取物、金合欢(Acacia Mill)提取物、光滑金虎尾(Malpighia glabra)提取物、苘麻(Abutilonavicennae)提取物、垂枝桦(Betula pendula)提取物、栎属(Quercus)五倍子(gallnut)提取物、日本栗(Castanea crenata)提取物、伞花异种白蜡花(Isodon umbrosusvar.leucanthus f.kameba)提取物、毛果香茶菜(Isodon trichocarpus)提取物、毛叶香茶菜(Rabdosia japonica(Burm.fil.)H.Hara)提取物、水芹(Oenanthe javanica)提取物、荞麦(Fagopyrum esculentum)提取物、海茸(Durvillaea antarctica)提取物、荠菜(Capsella bursa-pastoris)提取物、白头婆(Eupatorium japonicum)提取物、桑科(Moraceae)提取物、栀子花(Gardenia jasminoides)提取物、东当归(Angelicaacutiloba)提取物、粉花地榆(Sanguisorba officinalis)提取物、苦参(Sophoraflavescens)提取物、日本艾蒿变种(Artemisia indica var.maximowiczii)提取物、忍冬(Lonicera japonica)提取物、黄檗(Phellodendron amurense)提取物、鱼腥草(Houttuynia cordata)提取物、茯苓(Poria cocos)提取物、薏米(Coix lacryma-jobivar.ma-yuen)提取物、短柄野芝麻(Lamium album L.var.barbatum)提取物、啤酒花(Humulus lupulus)提取物、野山楂(Crataegus cuneata)提取物、桉树(Eucalyptus)提取物、洋蓍草(Achillea millefolium)提取物、蜀葵属(Althaea)提取物、少花桂(Cinnamomumloureiri Nees)提取物、单叶蔓荆(Vitex rotundifolia L.fil.)提取物、北美金缕梅(Hamamelis virginiana)提取物、鸡桑(Morus australis)提取物、桔梗(Platycodongrandiflorum)提取物、续随子(Euphorbia lathyris L.)提取物、日本鳶尾(Irisjaponica)提取物、中麻黃(Ephedra intermedia)提取物、蛇床子(Cnidium officinaleMakino)提取物、九眼独活(Aralia cordata)提取物、柴胡属(Bupleurum)/刺芹属(Eryngium)提取物、防风(Saposhnikovia divaricata)提取物、珊瑚菜(Glehnialittoralis)提取物、黄芩(Scutellaria baicalensis)提取物、芍药根皮提取物、芍药(Paeonia lactiflora Paeonia)提取物、童氏老鹳草(Geranium thunbergii)提取物、野葛根(Pueraria lobata)提取物、乌拉尔甘草(Glycyrrhiza uralensis)根提取物、盐肤木(Rhus javanica)提取物、库拉索芦荟(Aloe barbadensis Miller)提取物、升麻(Cimicifugae rhizoma)提取物、红花(Carthamus tinctorius)提取物、绿茶提取物、红茶提取物、儿茶钩藤(Uncaria gambir)提取物、德国洋甘菊(Matricaria recutita)提取物、蓼蓝(Persicaria tinctoria)提取物、油溶性光果甘草(Glycyrrhiza glabra)(甘草)根提取物、西河柳(Cacumen Tamaricis)提取物、虎耳草(Saxifraga stolonifera)提取物或它们的组合。
在一些实施方案中,该至少一种增白剂可以是氢醌、曲酸或它们的组合。
在一些实施方案中,该组合物还可包含约35重量%至约75重量%的至少一种表面活性剂。在一些实施方案中,该组合物可包含约25重量%至约80重量%的至少一种表面活性剂、约30重量%至约75重量%的至少一种表面活性剂、约35重量%至约70重量%的至少一种表面活性剂、约40重量%至约65重量%的至少一种表面活性剂或约50重量%至约60重量%的至少一种表面活性剂。在一些实施方案中,该组合物可以包含按重量计约25%、约30%、约35%、约40%、约45%、约50%、约55%、约60%、约65%、约70%、约72%、约75%或约80%的至少一种表面活性剂。
在一些实施方案中,该至少一种表面活性剂可以是天然表面活性剂,诸如甘油硬脂酸酯柠檬酸酯、鲸蜡醇磷酸酯钾、氢化棕榈甘油酯、甘油油酸酯柠檬酸酯、辛酸/癸酸甘油三酯、月桂基葡糖苷、癸基葡糖苷、辛酰基/癸酰基葡糖苷、椰油基葡糖苷、油酸甘油酯、椰油酰谷氨酸钠、椰油酰谷氨酸二钠、硬脂酰谷氨酸钠、月桂酰谷氨酸钠、肉豆蔻酰谷氨酸钠、椰油基甜菜碱、椰油酰胺丙基甜菜碱、椰油酰两性基二乙酸二钠、辛酰基癸酰基麦麸/稻草糖苷、杏仁油(压制或精制的)、刺阿甘树核油、脱水山梨糖醇硬脂酸酯、山梨糖醇月桂酸酯、鳄梨(Persea gratissima)油、甘油硬脂酸酯柠檬酸酯、阿甘油酰基两性基乙酸钠(sodiumarganamphoacetate)、巴巴苏油酰基两性基乙酸钠(sodium babassuamphoacetate)、可可脂两性基乙酸钠(sodium cocoabutteramphoacetate)、棉籽油酰基两性基乙酸钠(sodiumcottonseedamphoacetate)、乳木果油酰基两性基乙酸钠(sodiumsheabutteramphoacetate)、芒果油酰基两性基乙酸钠(sodiummangoamphoacetate)、橄榄油酰基两性基乙酸钠(sodium olivamphoacetate)、米糠油酰基两性基乙酸钠(sodiumricebranamphoacetate)、甜扁桃油酰基两性基乙酸钠(sodiumsweetalmondamphoacetate)、葵花籽油酰基两性基乙酸钠(sodiumsunflowerseedamphoacetate)、椰油醇-辛酸酯、鲸蜡醇、硬脂醇、油酸甘油酯、可可(Theobroma cacao)籽油、椰油酸钾、硬脂酰乳酸钠、阿拉伯胶树胶、水解根瘤菌胶、聚甘油-10月桂酸酯、聚甘油-3椰油酸酯、聚甘油-3聚蓖麻油酸酯、聚甘油-3蓖麻油酸酯、芸苔油醇异亮氨酸酯乙磺酸胺、芸苔醇、聚甘油-3亚麻酸山梨醇酯、油橄榄(Olea europaea)果油、椰油基甲基葡糖酰胺、月桂酰燕麦氨基酸钠、藜麦(Chenopodium quinoa)籽提取物、椰油醇、聚甘油基-10十油酸酯、聚甘油基-10月桂酸酯、聚甘油基-10肉豆蔻酸酯、聚甘油基-10油酸酯、聚甘油基-10棕榈酸酯、聚甘油基-10硬脂酸酯、聚甘油基-10二硬脂酸酯、聚甘油基-10三硬脂酸酯、聚甘油基-10五油酸酯、聚甘油基-10五硬脂酸酯、聚甘油基-10七羟基硬脂酸酯、庚基葡糖苷、芝麻(Sesamumindicum)籽油、甜杏仁油聚甘油基-6酯、杏仁油聚甘油基-10酯、杏仁油聚甘油基-6酯、阿甘油聚甘油基-6酯、巴巴苏油聚甘油基-6酯、猴面包树(Adansonia digitata)籽油聚甘油基-6酯、椰子油聚甘油基-6酯、西瓜籽油聚甘油基-6酯、吐根椴树(Trichilia emetica)籽油聚甘油基-6酯、伯尔硬胡桃(Sclerocarya birrea)油聚甘油基-6酯、曼杰提树(Schinziophyton rautanenii)籽油聚甘油基-6酯、莫诺伊油(oil)聚甘油基-6酯、油酸葵花油聚甘油基-10酯、油酸葵花油聚甘油基-6酯、橄榄油聚甘油基-6酯、红花籽油聚甘油基-6酯、乳木果油聚甘油基-6酯、海檀木(Ximeniaamericana)籽油聚甘油基-6酯、山梨醇酐棕榈酸酯、葵花油酰基甲基葡糖胺、月桂酰葡糖苷羟丙基磺酸钠、椰油酰氨基丙基羟基磺基甜菜碱或它们的组合。
在一些实施方案中,该至少一种表面活性剂可以是脱水山梨糖醇单月桂酸酯、椰油脂肪酸脱水山梨糖醇、脱水山梨糖醇二硬脂酸酯、脱水山梨糖醇单硬脂酸酯、脱水山梨糖醇三硬脂酸酯、脱水山梨糖醇单异硬脂酸酯、脱水山梨糖醇单油酸酯、脱水山梨糖醇三油酸酯、脱水山梨糖醇脂肪酸酯、脱水山梨糖醇单棕榈酸酯、脱水山梨糖醇倍半油酸酯、脱水山梨糖醇倍半硬脂酸酯、聚氧乙烯脱水山梨糖醇单月桂酸酯、聚氧乙烯脱水山梨糖醇单硬脂酸酯、乙二醇单硬脂酸酯、乙二醇二硬脂酸酯、二乙二醇二硬脂酸酯、乙二醇脂肪酸酯、甘油单硬脂酸酯、甘油二硬脂酸酯、甘油异硬脂酸酯、聚氧乙烯甘油异硬脂酸酯、聚氧乙烯甘油三异硬脂酸酯、二甘油异硬脂酸酯、甘油二异硬脂酸酯、甘油三异硬脂酸酯、二甘油三异硬脂酸酯、丙二醇单硬脂酸酯、自乳化丙二醇硬脂酸酯、甘油蓖麻醇酸酯、丙二醇蓖麻醇酸酯、丙二醇脂肪酸酯、丙二醇二油酸酯、丙二醇月桂酸酯、甘油亚油酸酯、甘油二异棕榈酸酯、甘油倍半油酸酯、甘油单油酸酯、甘油三肉豆蔻酸酯、羊毛脂酸异丙酯、辛酸己基癸基二甲酯、乙酰甘油、三异辛酸甘油酯、二-2-庚基十一酸甘油酯、单丙谷氨酸单油酸甘油酯、十油酸十甘油酯、二季戊四酸脂肪酸酯、甘油硬脂酸酯/苹果酸酯、聚氧乙烯氢化蓖麻油、聚氧乙烯烷基(12-14)醚(7E.O.)、聚氧乙烯烷基醚(12-14)醚(12E.O.)、聚氧乙烯烷基醚(20E.O.)、聚氧乙烯月桂基醚、聚氧乙烯肉豆蔻醚、聚氧乙烯十六烷基醚、聚氧乙烯十六十八烷基醚、聚氧乙烯十八烷基醚、聚氧乙烯油基醚、聚氧乙烯油基十六烷基醚、聚氧乙烯山嵛基醚、聚氧乙烯辛基苯基醚、聚氧乙烯壬基苯基醚、聚氧乙烯烷基(12,13)醚(10E.O.)、聚氧乙烯辛基十二烷基醚、聚氧乙烯鲸蜡基硬脂基双醚、聚氧乙烯甲基葡萄糖苷倍半硬脂酸酯、羧化聚氧乙烯十三烷基醚、聚乙二醇-4辛酸酯和聚(氧乙烯)壬基苯基醚(14E.O.)的混合物、聚氧乙烯羊毛脂醇、聚氧乙烯(5)羊毛脂醇、聚氧乙烯(10)羊毛脂醇、聚氧乙烯(15)羊毛脂醇、聚氧乙烯(20)羊毛脂醇、聚氧乙烯(25)羊毛脂醇、聚氧乙烯(40)羊毛脂醇、聚氧乙烯(烷基醇/羊毛脂醇)醚(16E.O.)、聚氧乙烯羊毛脂醇乙酸酯、聚氧乙烯羊毛脂、聚氧乙烯氢化羊毛脂、聚氧乙烯山梨醇羊毛脂(40E.O)、聚氧乙烯聚氧丙烯氢化羊毛脂、聚氧乙烯聚氧丙烯羊毛脂、聚氧乙烯聚氧丙烯羊毛脂油、聚氧乙烯硬脂酸酰胺、聚氧乙烯植物甾醇、聚氧乙烯二壬基苯基醚、聚乙二醇单月桂酸酯、聚乙二醇二月桂酸酯、聚乙二醇棕榈酸酯、聚乙二醇二棕榈酸酯、聚乙二醇二棕榈酸酯、聚乙二醇单油酸酯、聚乙二醇150二油酸酯、聚乙二醇单硬脂酸酯、聚乙二醇二硬脂酸酯、聚氧乙烯甘油三硬脂酸酯、聚乙二醇300羊毛脂脂肪酸、聚乙二醇600羊毛脂脂肪酸、聚乙二醇1000羊毛脂脂肪酸、聚乙二醇(36)单油酸酯、聚氧乙烯(20E.O.)脱水山梨糖醇单月桂酸酯、聚氧乙烯(20E.O.)椰子油脂肪脱水山梨糖醇酯、聚氧乙烯(20E.O.)脱水山梨糖醇棕榈酸酯、聚氧乙烯(40E.O.)脱水山梨糖醇油酸酯、聚氧乙烯(6E.O.)脱水山梨糖醇单油酸酯、聚氧乙烯(20E.O.)脱水山梨糖醇单油酸酯、聚氧乙烯脱水山梨糖醇单月桂酸酯、聚氧乙烯脱水山梨糖醇四油酸酯、聚氧乙烯(20E.O.)脱水山梨糖醇三油酸酯、聚氧乙烯(6E.O.)脱水山梨糖醇单硬脂酸酯、聚氧乙烯(6E.O.)脱水山梨糖醇三硬脂酸酯、聚氧乙烯脱水山梨糖醇六硬脂酸酯、聚氧乙烯(3E.O.)脱水山梨糖醇异硬脂酸酯、聚氧乙烯甘油单硬脂酸酯、山梨醇聚醚-6蜂蜡、聚氧乙烯聚氧丙烯丁基醚、聚氧乙烯(20)聚氧丙烯(15)丁基醚、聚氧乙烯(35)聚氧丙烯(28)丁基醚、聚氧乙烯(36)聚氧丙烯(36)丁基醚、聚氧乙烯(37)聚氧丙烯(38)丁基醚、聚氧乙烯聚氧丙烯十六烷基醚、聚氧乙烯聚氧丙烯十二烷基十四烷基醚、聚氧乙烯聚氧丙烯低聚琥珀酸酯(3E.O.)(20P.O.)、聚氧乙烯聚氧丙烯己二醇醚(300E.O.)(75P.O.)、三甲基丙烷三(聚氧乙烯异硬脂酸酯)(3E.O.)、甘油聚氧乙烯油酸酯、聚氧乙烯(10)聚氧丙二醇(30)、聚氧乙烯(16)聚氧丙二醇(30)、聚氧乙烯(25)聚氧丙二醇(30)、聚氧乙烯(160)聚氧丙二醇(30)、聚氧乙烯(30)聚氧丙二醇(35)、聚氧乙烯(200)聚氧丙二醇(40)、聚氧乙烯(200)聚氧丙二醇(70)、聚氧乙烯(20)聚氧丙二醇(15)丁基醚、聚氧乙烯(6)聚氧丙二醇(30)、聚氧乙烯(1)聚氧丙烯(4)十六烷基醚、聚氧乙烯(1)聚氧丙烯(8)十六烷基醚、聚氧乙烯(20)聚氧丙烯(4)十六烷基醚、聚氧乙烯(20)聚氧丙烯(8)十六烷基醚、聚氧丙烯(9)二甘油基醚、聚氧丙烯硬脂基醚、四(聚氧乙烯聚氧丙烯)乙二胺、聚氧乙烯(6E.O.)癸酸/辛酸甘油酯、聚氧乙烯甘油月桂酸酯、聚氧乙烯甘油基椰油脂肪酸酯、聚氧乙烯二乙醇胺月桂酸酯(4E.O.)、二辛基十二烷醇月桂酰谷氨酸酯、二聚氧乙烯硬脂酰醚二酯月桂酰谷氨酸酯、聚氧乙烯辛基十二烷基醚二酯月桂酰谷氨酸酯、聚氧乙烯甘油基焦谷氨酸异硬脂酸酯、PEG-40氢化蓖麻油PCA异硬脂酸酯、癸酸二乙醇胺、十一烯酸单乙醇酰胺、椰油脂肪酸单乙醇酰胺、椰油脂肪酸二乙醇酰胺(1:2型)、椰油脂肪酸二乙醇酰胺、月桂酸乙醇酰胺、月桂酸二乙醇酰胺、月桂酸异丙醇酰胺、月桂酰胺/肉豆蔻酰胺二乙醇酰胺(DEA)、月桂酰胺/肉豆蔻酰胺三乙醇酰胺(TEA)、肉豆蔻酸二乙醇酰胺、棕榈酸乙醇酰胺、硬脂酸单乙醇酰胺、硬脂酸二乙醇酰胺、硬脂酸二乙基氨基乙胺、异硬脂酸二乙醇酰胺、油酸二乙醇酰胺、亚油酸二乙醇酰胺、牛脂酰胺单乙醇酰胺、牛脂酰胺二乙醇酰胺、氢化牛脂酰胺二乙醇酰胺、羊毛脂酰胺二乙基酰胺、聚氧乙烯椰油脂肪酰胺(5E.O.)、聚氧乙烯(2)椰油脂肪酸单乙醇酰胺、聚氧乙烯(5)椰油脂肪酸单乙醇酰胺、聚氧乙烯(10)椰油脂肪酸单乙醇酰胺、聚氧乙烯椰油脂肪酸二乙醇酰胺、聚氧乙烯牛油烷基二乙醇胺(2E.O.)、聚氧乙烯椰油烷基二甲胺氧化物、椰油烷基二甲胺氧化物液体、油基二甲胺氧化物、二羟乙基月桂胺氧化物、季戊四醇松香酸酯、六甘油油酸酯、甲基葡萄糖倍半硬脂酸酯、聚乙二醇单油酸酯、聚乙二醇烷基化物、聚乙烯烷基醚、聚二醇二醚、月桂酰二乙醇酰胺、脂肪酸异丙醇酰胺、麦芽糖醇羟基脂肪酸醚、烷基化多糖、烷基葡糖苷;海藻糖单脂肪酸醚,诸如海藻糖单肉豆蔻酸酯、海藻糖单异硬脂酸酯、海藻糖单十一酸酯;聚氧乙烯甲基葡糖苷二油酸酯(120E.O.);糖酯,诸如蔗糖脂肪酸酯、椰油酸甘油酯或它们的组合。
在一些实施方案中,该至少一种表面活性剂可以是非离子表面活性剂,诸如亲脂性甘油单硬脂酸酯、自乳化甘油单硬脂酸酯、聚甘油单硬脂酸酯、聚甘油烷基化物、脱水山梨糖醇单油酸酯、聚乙二醇单硬脂酸酯、聚氧乙烯脱水山梨糖醇单油酸酯、聚氧乙基化甾醇、聚氧乙基化羊毛脂、聚氧乙基化蜂蜡、聚氧乙烯氢化蓖麻油、甘油脂肪酸酯、聚甘油脂肪酸酯、聚氧乙烯脱水山梨糖醇脂肪酸酯、聚氧乙烯山梨糖醇脂肪酸酯、聚氧乙烯甘油脂肪酸酯、聚氧乙烯烷基醚、聚氧乙烯脂肪酸酯、聚氧乙烯氢化蓖麻油、聚氧乙烯蓖麻油、聚氧乙烯-聚氧丙烯共聚物、聚氧乙烯-聚氧丙烯烷基醚、聚醚改性的硅酮月桂酸烷醇酰胺、烷基胺氧化物、氢化大豆磷脂、辛酰基葡糖苷、甘油柠檬酸脂肪酸酯、甘油硬脂酸酯柠檬酸酯、玉米油PEG-8酯、椰油酰胺DEA、椰油酰胺MEA、椰油酰胺MIPA、蔗糖四硬脂酸酯三乙酸酯、氢化棕榈仁甘油酯、氢化棕榈PEG-200甘油酯、氢化棕榈甘油酯、脱水山梨糖醇倍半异硬脂酸酯、聚甘油-2倍半异硬脂酸酯、聚甘油-2倍半辛酸酯、PEG-20甲基葡萄糖倍半硬脂酸酯或它们的组合。
在一些实施方案中,该至少一种表面活性剂可以是阴离子表面活性剂,诸如硬脂酸钠、硬脂酸锌、硬脂酸钙、硬脂酸镁、硬脂酸铝、异硬脂酸铝、硬脂酸三乙醇胺、棕榈酸钾、十六烷基硫酸钠、月桂基磷酸钠、月桂基磷酸二钠、棕榈酸三乙醇胺、聚氧乙烯月桂基磷酸钠、N-酰基谷氨酸钠、棕榈酸钠、月桂酸钠、月桂酸钾、月桂酸锌、月桂酸三乙醇胺、月桂酸钠、月桂基硫酸钠、月桂基硫酸钾、月桂基硫酸铵、单乙醇胺月桂基硫酸酯、二乙醇胺月桂基硫酸酯、三乙醇胺月桂基硫酸酯、月桂基二氨基乙基甘氨酸钠、三乙醇胺醚烷基硫酸酯、土耳其红油、直链十二烷基苯磺酸酯、聚氧乙烯氢化蓖麻油马来酸酯、酰基甲基牛磺酸酯、脂肪酸皂、α-酰基磺酸酯、烷基磺酸酯、烷基烯丙基磺酸酯、烷基萘磺酸酯、烷基硫酸酯、POE烷基醚硫酸酯、烷基酰胺硫酸酯、烷基磷酸酯、POE烷基磷酸酯、烷基酰胺磷酸酯、烷基酰烷基牛磺酸酯、N-酰基氨基酸盐、POE烷基醚碳酸酯、烷基磺基琥珀酸酯、烷基磺基乙酸钠、酰基羟乙基磺酸酯、酰基化氢化胶原肽盐、全氟烷基磷酸酯、皂条、钾皂、十一烯酸锌、含钾皂条、椰油脂肪酸钾、磺化蓖麻油、肉豆蔻酸钠、肉豆蔻酸钾、肉豆蔻酸锌、肉豆蔻酸镁、油酸钠、油酸钾、N-酰基-L-谷氨酸三乙醇胺、N-酰基-L-谷氨酸钠、N-椰油脂肪酸酰基-L-谷氨酸钠、N-椰油脂肪酸/氢化牛脂酸酰基-L-谷氨酸钠、N-椰油脂肪酸酰基-L-谷氨酸三乙醇胺、硬脂酰-L-谷氨酸二钠、N-氢化牛脂酸酰基-L-谷氨酸钠、N-月桂酰基-L-谷氨酸钠、N-硬脂酰基-L-谷氨酸、N-月桂酰基-L-赖氨酸、月桂酰基-L-谷氨酸三乙醇胺、L-精氨酸乙基·DL-吡咯烷酮羧酸盐、N-椰油脂肪酸酰基-L-精氨酸乙基·DL-吡咯烷酮碳酸盐、椰油酰肌氨酸、椰油酰肌氨酸钠、N-(椰油酰)肌氨酸三乙醇胺盐、月桂酰肌氨酸、月桂酰肌氨酸钠、月桂酰肌氨酸三乙醇胺、羧化聚氧乙烯十三烷基醚钠(3E.O.)、β-月桂基氨基丙酸钠、月桂基氨基丙酸溶液、甲基椰油酰基牛磺酸钾、甲基椰油酰基牛磺酸钠、月桂酰甲基牛磺酸钠、月桂基磺基乙酸钠、椰油基甲基丙氨酸钠溶液、椰油基三乙醇胺溶液、月桂酰基甲基-β-丙氨酸钠溶液、月桂基-N-羧基甲氧基乙基-N-羧基甲基-咪唑啉鎓十二烷酰肌氨酸二钠、可可烷基-N-羧乙基-N-羟基咪唑甜菜碱钠、可可烷基-N-羧基乙氧基乙基-N-羧基乙基-咪唑氢氧化铵二钠、可可烷基-N-羧基甲氧基乙基-N-羧基甲基-咪唑啉鎓氢氧化二钠、可可烷基-N-羧基甲氧基乙基-N-羧基甲基-咪唑啉鎓月桂酰硫酸二钠、肉豆蔻酰甲基-β-丙氨酸钠溶液、甲基硬脂酰牛磺酸钠、十四烯磺酸钠、十二烷基苯磺酸钠、三乙醇胺十二烷基苯磺酸盐、石油磺酸钠、烷基硫酸铵、辛基苯氧基二氧基乙基磺酸钠、三乙醇胺/可可烷基硫酸镁、肉豆蔻基硫酸钠、十六十八烷基硫酸纳、油醇硫酸酯钠、三乙醇胺油醇硫酸酯、聚氧乙烯十二烷基醚硫酸钠、聚氧乙烯十二烷基醚硫酸铵(2E.O.)、三乙醇胺聚氧乙烯十二烷基醚硫酸盐、聚氧乙烯烷基醚硫酸铵(3E.O.)溶液、二乙醇胺聚氧乙烯烷基醚硫酸盐(3E.O.)溶液、三乙醇胺聚氧乙烯烷基醚硫酸盐(3E.O.)溶液、聚氧乙烯烷基醚硫酸钠(3E.O.)溶液、椰油酸单甘油酯硫酸钠、聚氧乙烯(5)椰子脂肪酸单乙醇酰胺磷酸盐;聚氧乙烯烷基(12-14)醚磷酸酯(2E.O.)、(8E.O.)、(10E.O.);聚氧乙烯月桂基醚磷酸盐、聚氧乙烯月桂基醚磷酸钠、聚氧乙烯十六烷基醚磷酸盐、聚氧乙烯十六烷基醚磷酸钠、聚氧乙烯十八烷基醚、聚氧乙烯胆甾醇醚、聚氧乙烯十八烷基醚磷酸盐、聚氧乙烯油基醚磷酸盐、聚氧乙烯油基醚磷酸钠、二乙醇胺聚氧乙烯油基醚磷酸盐、聚氧乙烯烷基苯醚磷酸盐、三乙醇胺聚氧乙烯烷基苯醚磷酸盐、聚氧乙烯-聚氧丙烯十六烷基醚磷酸盐、聚氧丙烯甘油醚磷酸盐、聚氧丙烯丁醚磷酸盐、月桂醇聚醚磺基琥珀酸二钠、椰油酰乙基酯磺酸钠、磺基琥珀酸二辛酯钠、辛基苯氧基二氧基乙基磺酸钠、十二烷基磺基琥珀酸二钠、油酸氨基磺基琥珀酸二钠、C12-15链烷醇聚醚-3磷酸酯、聚氧乙烯烷基(C12-14)磺基琥珀酸钠(7E.O.)、月桂酰胺基PEG-5磺基琥珀酸二钠(5E.O.)、异硬脂酰乳酰乳酸钠、十一碳烯酰水解胶原钠、十一碳烯酰水解胶原钾、2-十一烷基-1-羟乙基咪唑啉鎓甜菜碱钠、月桂酰水解胶原钠、椰油酰水解胶原钠、椰油酰水解胶原钾、椰油酰水解胶原钾溶液、TEA-椰油酰水解胶原、异硬脂酰水解胶原、异硬脂酰水解蚕丝、AMPD-异硬脂酰水解胶原、乙二胺-N,N,N',N'-四(2-羟丙基)二油酸酯、十二烷酰肌氨酸、月桂亚氨基二丙酸钠(30%)、油酰肌氨酸、肉豆蔻酰β-丙氨酸钠溶液、十一烷基羟乙基咪唑啉鎓甜菜碱钠、C12,13,16烷基硫酸铵、三乙醇胺硫酸烷基(11,13,15)酯(1)、三乙醇胺硫酸烷基(11,13,15)酯(2)、三乙醇胺硫酸烷基(12-15)酯、三乙醇胺硫酸烷基(12-14)酯、烷基(12,13)硫酸钠、三乙醇胺聚氧乙烯烷基醚硫酸盐(3E.O.)溶液、C11-15烷醇聚醚-3硫酸钠、C12-13烷醇聚醚-3硫酸钠、C12-15烷醇聚醚-3硫酸钠、TEA C12-13烷醇聚醚-3硫酸盐、TEA/Na C12-13烷醇聚醚-3硫酸盐、PEG-3钴酰胺硫酸钠、PEG-5钴酰胺磷酸钠、PEG-5十二烷基柠檬酸磺基琥珀酸二钠、PPG-5-鲸蜡醇聚醚-10、PEG-25磷酸丁酯、C14-18烷基磺酸钠、C20-22磷酸烷基酯、异月桂醇聚醚-4磷酸酯、十一碳烯酰甘氨酸、橄榄脂肪酸钾、油酰肌氨酸、油基甲基牛磺酸钠、油醇聚醚-3磷酸酯、油醇聚醚-4磷酸酯、油醇聚醚-5磷酸酯、油醇聚醚-10磷酸酯、油醇聚醚-20磷酸酯、油醇聚醚-7磷酸钠、油醇聚醚-8磷酸钠、C14-16烯烃磺酸钠、辛酰甘氨酸;椰油酰谷氨酸盐,诸如椰油酰氨基酸钠、椰油酰丙氨酸三乙醇胺、椰油酰羟乙基磺酸钠、椰油酰羟乙基磺酸铵、椰油酰甘氨酸钾、椰油酰甘氨酸钠、椰油酰谷氨酸三乙醇胺、椰油酰谷氨酸、椰油酰谷氨酸二钠和椰油酰谷氨酸钾;椰油酰肌氨酸、椰油酰肌氨酸钠、椰油酰肌氨酸三乙醇胺、椰油酰牛磺酸钠、椰油酰甲基β-丙氨酸、椰油酰甲基β-丙氨酸钠、甲基椰油酰牛磺酸酯、甲基椰油酰牛磺酸钾、甲基椰油酰牛磺酸镁、甲基椰油酰牛磺酸钠、椰油酰苹果氨基酸钠、椰油醇聚醚硫酸酯钠、二-C11-15烷醇聚醚-2磷酸酯、二-C12-15烷醇聚醚-4磷酸酯、二-C12-15烷醇聚醚-8磷酸酯、二-C12-15烷醇聚醚-10磷酸酯、二油基磷酸酯、二油醇聚醚-8磷酸钠、二油醇聚醚-8磷酸钠、二椰油酰乙二胺PEG-15硫酸钠、二月桂醇聚醚-10磷酸钠、硬脂醇聚醚-2磷酸酯、硬脂醇聚醚-3磷酸酯、硬脂酰乳酸钙、硬脂酰乳酸钠、十一碳烯酰胺MEA-磺基琥珀酸二钠、月桂酰胺基MEA-磺基琥珀酸二钠、月桂醇聚醚磺基琥珀酸二钠、DEA-鲸蜡基磷酸酯、鲸蜡基磷酸钾、鲸蜡基硬脂酰基硫酸酯钠、鲸蜡醇聚醚-10磷酸酯、鲸蜡醇聚醚-20磷酸酯、三鲸蜡硬脂醇聚醚-4磷酸酯、十三烷醇聚醚-4羧酸、十三烷醇聚醚-8羧酸、十三烷醇聚醚-4羧酸钠、十三烷醇聚醚-7羧酸钠、十三烷醇聚醚-3羧酸钠、十三烷醇聚醚-3羧酸钾、三月桂醇聚醚-4磷酸酯、油醇乳酸酯、棕榈酰谷氨酸钠、棕榈酰谷氨酸镁、棕榈酰肌氨酸钠、棕榈酰脯氨酸、棕榈酰脯氨酸钠、甲基棕榈酰牛磺酸钠、肉豆蔻酰谷氨酸钾、肉豆蔻酰谷氨酸钠、肉豆蔻酰肌氨酸钠、甲基肉豆蔻酰牛磺酸钠、椰酸钾、椰酸三乙醇胺、椰酸精氨酸、月桂亚氨基二乙酸二钠、月桂基甘醇羧酸钠、月桂醇聚醚-5羧酸、月桂醇聚醚-6羧酸、月桂醇聚醚-11羧酸、月桂醇聚醚-5羧酸钠、月桂醇聚醚-6羧酸钠、月桂醇聚醚-11羧酸钠、月桂醇聚醚-5乙酸盐、月桂醇聚醚-6乙酸盐、月桂醇聚醚-4,5乙酸钾、月桂醇聚醚-3乙酸钠、月桂醇聚醚-4乙酸钠、月桂醇聚醚-5乙酸钠、月桂醇聚醚-6乙酸钠、月桂醇聚醚-11乙酸钠、MIPA-月桂醇聚醚硫酸盐、月桂醇聚醚硫酸钠、三乙醇胺月桂醇聚醚硫酸盐、月桂醇聚醚-2硫酸铵、月桂醇聚醚-3硫酸铵、月桂醇聚醚-1磷酸盐、月桂醇聚醚-2磷酸盐、月桂醇聚醚-4磷酸盐、月桂酰天冬氨酸钠、月桂基燕麦氨基酸钠、月桂酰乳酸钠、N-月桂酰-N-甲基-β-丙氨酸钾盐、TEA-月桂酰甲基氨基丙酸酯、二鲸蜡醇磷酸酯、鲸蜡醇磷酸酯或它们的组合。
在一些实施方案中,该至少一种表面活性剂可以是阳离子表面活性剂,诸如月桂基三甲基氯化铵、二椰油基二甲基氯化铵、肉豆蔻基二甲基苄基氯化铵、鲸蜡基三甲基氯化铵、月桂基吡啶鎓氯化物、鲸蜡基吡啶鎓氯化物、苄索氯铵、硬脂基三甲基氯化铵、苯扎氯胺、苯扎氯铵液、月桂基胺氧化物、烷基三甲基氯化铵、硬脂基三甲基氯化铵、硬脂基二甲基苄基氯化铵、二甲基硬脂基氯化铵处理过的锂蒙脱石、苄基二甲基硬脂基氯化铵处理过的锂蒙脱石、二硬脂基二甲基氯化铵、苄基二甲基硬脂基氯化铵处理过的锂蒙脱石、二硬脂基二甲基氯化铵、二硬脂基二甲基氯化铵处理过的膨润土、二烷基二甲基氯化铵、三(聚氧乙烯)硬脂基氯化铵(5E.O.)、二(聚氧乙烯)油基甲基氯化铵(2E.O.)、N-(硬脂酰基胆氨基甲酰基甲基)吡啶鎓氯化物、聚氧丙烯甲基二乙基氯化铵、烷基二氨基乙基甘氨酸盐酸盐溶液、溴化烷基异喹啉氮鎓溶液、月桂基三甲基溴化铵、十六烷基三甲基溴化铵、硬脂基三甲基溴化铵、十六烷基三甲基糖精铵、硬脂基三甲基糖精铵、聚乙二醇·环氧氯丙烷·椰子烷基胺·二丙烯三胺缩合物、聚乙二醇·环氧氯丙烷·牛脂烷基胺·二丙烯三胺缩合物、硫酸乙酯羊毛脂脂肪酸氨基丙基乙基二甲基铵(1)、(2);山榆基三甲基溴化铵、山榆酸酰胺丙基二甲基羟丙基氯化铵、硬脂酸二乙基氨基乙基酰胺、硬脂酸二乙基氨基乙基酰胺、硬脂酸二甲基氨基丙基酰胺、羊毛脂衍生物季铵盐、PEG-5油胺、PEG-2油基甲基氯化铵、PEG-2椰油胺、PEG-3椰油胺、PEG-5椰油胺、PEG-10椰油胺、PEG-15椰油胺、PEG-2二白池花籽油酰胺乙基甲基铵甲基硫酸盐、羟丙基精氨酸月桂基/肉豆蔻基醚HCl、鲸蜡硬脂基三甲基氯化铵、C10-40异烷酰胺丙基乙基二甲基铵乙基硫酸盐、异硬脂基乙基咪唑鎓乙基硫酸酯、刺云实羟丙基三甲基氯化铵、季铵盐-33、季铵盐-91、椰油酰胺丙基PG-二甲基氯化铵磷酸酯、椰油酰胺丙基甜菜碱酰胺MEA氯化物、PCA椰油酰精氨酸乙酯、椰油基三甲基铵甲基硫酸盐、胡芦巴羟丙基三甲基氯化铵、肉豆蔻/棕榈酰胺丁基胍乙酸盐、二-C12-18烷基二甲基氯化铵、二椰油酰乙基羟乙基甲基铵甲基硫酸盐、二椰油基二甲基氯化铵、二硬脂基二甲基氯化铵、二硬脂酰乙基羟乙基甲基铵甲基硫酸盐、二鲸蜡基二甲基氯化铵、二棕榈酰氧乙基羟乙基甲基铵甲基硫酸盐、二羟丙基PEG-5亚油基氯化铵、二甲基PABA酰胺丙基月桂基二甲基铵甲苯磺酸盐、二甲基硬脂基胺、硬脂酰胺乙基二乙胺、硬脂酰胺丙基二乙胺、硬脂基烷基氯化铵、硬脂基三甲基铵糖精酸盐、硬脂基三甲基氯化铵、硬脂基三甲基溴化铵、硬脂氧基丙基三甲基氯化铵、西他氯铵、氯化鲸蜡基吡啶鎓、西曲氯铵、西曲溴铵、西曲铵甲基硫酸盐、大豆油基三甲基氯化铵、棕榈酰胺丙基三甲基氯化铵、泛醇基羟丙基硬脂基二甲基氯化铵、羟乙基鲸蜡基二甲基磷酸铵、羟丙基三甲基氯化铵蜂蜜、羟丙基双-羟乙基二甲基氯化铵、山嵛酰胺丙基二甲胺、山嵛酰胺丙基二甲胺、山嵛三甲基氯化铵、山嵛基三甲基铵甲基硫酸盐、泊洛沙胺701、泊洛沙胺702、泊洛沙胺704、双羟乙基双鲸蜡基马来酰胺、棕榈油烷基PG二甲基氯化铵磷酸钠、月桂基三甲基氯化铵、月桂基吡啶鎓氯化物、亚油胺丙基PG-二甲基氯化铵磷酸酯或它们的组合。
在一些实施方案中,该至少一种表面活性剂可以是两性表面活性剂,诸如羧基甜菜碱、酰胺甜菜碱、磺基甜菜碱、羟基磺基甜菜碱、酰胺基磺基甜菜碱、磷甜菜碱、氨基羧酸盐、咪唑啉衍生物和酰胺胺型,包括月桂基二甲基氨基乙酸甜菜碱、2-烷基-N-羧甲基-N-羟乙基咪唑啉鎓甜菜碱、十一烷基-N-羟乙基-N-羧基甲基咪唑啉鎓甜菜碱、棕榈油烷基甜菜碱、椰油酰氨基丙基甜菜碱、硬脂基二羟乙基甜菜碱、硬脂基二甲基氨基乙酸甜菜碱、双(硬脂基-N-羟乙基咪唑啉鎓)氯乙酸络合物、椰油酰基水解胶原、油酰基水解胶原、十六烷基水解胶原、月桂酰胺丙基甜菜碱/水、肉豆蔻酰水解胶原、烷基氨基乙基甘氨酸氯化物溶液和卵磷脂;和其他,包括PEG-3月桂基胺氧化物、油胺氧化物、油基甜菜碱、辛酰/癸酰氨丙基甜菜碱、椰油胺氧化物、椰油酰两性基乙酸钠、椰油酰两性基二乙酸钠、椰油酰两性基二乙酸二钠、椰油酰两性基丙酸钠、二羟乙基月桂胺氧化物、硬酯胺氧化物、硬脂基甜菜碱、棕榈仁酰胺乙基羟乙基氨基丙酸钠、棕榈仁酰胺丙基甜菜碱、C12-14羟烷基羟乙基β-丙氨酸、七羟乙基羧酸甲基咪唑啉鎓氯化物/七癸基双羟乙基咪唑啉鎓、肉豆蔻酰胺丙基甜菜碱、肉豆蔻胺氧化物、肉豆蔻基甜菜碱、月桂酰胺丙基氧化胺、月桂酰胺丙基羟基磺基甜菜碱、月桂酰胺丙基甜菜碱、月桂氨基丙酸钠、月桂胺氧化物、月桂亚氨基二丙酸钠、月桂基羟基磺基甜菜碱、月桂基甜菜碱、月桂酰两性基乙酸钠和月桂酰赖氨酸;七叶皂苷、表面活性素钠、皂苷、羟基化卵磷脂、氢化溶血卵磷脂、氢化卵磷脂、脑磷脂、磷脂酰丝氨酸、溶血卵磷脂、磷脂、卵磷脂或它们的组合。
在一些实施方案中,该至少一种表面活性剂可以是月桂基葡糖苷羟丙基磺酸钠盐、椰油酰胺丙基羟基磺基甜菜碱、椰油基谷氨酸钠盐或它们的组合。
在一些实施方案中,该组合物还可包含至少一种抗微生物剂。示例性的抗微生物剂包括苯氧乙醇、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯或它们的组合。
在一些实施方案中,该组合物还可包含至少一种抗炎剂。在一些实施方案中,该抗炎剂可以是植物来源的化合物,诸如尿囊素、金缕梅、芦荟、洋甘菊、百里香提取物、紫锥花、马齿苋提取物或它们的组合。
在一些实施方案中,组合物可包含至少一种收敛剂。在一些实施方案中,该至少一种收敛剂可以是柠檬酸、鞣酸、乙酰氧基丙酸、异戊酸、氨基戊酸、乙氧基乙酸、乙氧基丙酸、异氨基戊酸、环氧油酸、反油酸、氨基丁酸、芥酸、草酰乙酸、甲酸、二十烷酸、葡糖醛酸、艾杜糖醛酸、巴豆酸、氯异巴豆酸、异巴豆酸、乙酸、二氢硫辛酸、酒石酸、乙基巴豆酸、二苯基乙酸、二甲氧基邻苯二甲酸、乙基羟基丁酸、琥珀酸、硬脂酸、硬脂酸、山梨酸、巴豆酸、甲状腺素、癸酸、托品酸、乳酸、羟基异丁酸、羟基戊酸、丙酮酸、乙酸丁酯、丁基过氧化氢、巴西烯酸、丙炔酸、丙酸、溴代异戊酸、溴代异丁酸、溴代异丙酸、己酸、己烯酸、岩芹酸、十七烷酸、庚酸、苯基马来酸(maleanilic acid)、马来酰胺酸(maleamic acid)、分枝菌酸、肉豆蔻酸、甲基丙烯酸、甲基戊酸、甲基硫乙酸、丁酸甲酯、甲羟戊酸、蜂花酸、巯基乙酸、碘乙酸、月桂酸、反蓖麻酸、蓖麻油酸、亚油酸、亚麻酸、乌头酸、草酰琥珀酸、氧代戊二酸、己二酸、钙黄绿素、羧苯基乙酸、乙酰氧基琥珀酸、吡啶三羧酸(carbocinchomeronic acid)、樟脑酸、异樟脑酸、戊烯二酸、戊二酸、异柠檬酸、藏花酸、琥珀酸、邻苯二甲酸、富马酸、异吡啶二羧酸(isocinchomeronic acid)、二亚乙基三胺五乙酸、间苯二酸、柠苹酸、烟碱二酸、衣康酸、二溴琥珀酸、二氯琥珀酸、乙基丙二酸、二甲基琥珀酸、草酸、吡啶二羧酸(cinchomeronicacid)、连苯三甲酸、壬酸、小檗三酸、苯六甲酸、苯五甲酸、马来酸、丙二酸、中康酸、中酒石酸、中草酸、甲基间苯二酸、甲基琥珀酸、甲基丙二酸、巯基琥珀酸、苯偏四甲酸、过苯二甲酸、苹果酸、卢剔啶酸、白三烯溴邻苯甲酸、氨基肉桂酸、异丙基肉桂酸、草酰胺酸、槟榔啶、羧酸肉桂酸、肉桂酸、没食子酸、氨甲环酸、硝基肉桂酸、羟基肉桂酸、甲氧基肉桂酸、羟基羟基肉桂酸、苯基肉桂酸、鞣花酸、乳清酸尿、樟脑酸、奎宁酸、羟脯氨酸、还原尿睾酸、大风子油酸、肌肽、咔唑乙酸、喹啉羧酸、喹啉酸、喹啉二羧酸、香豆酸、氯苯氧乙酸、鹅去氧胆酸、胆烷酸、胆酸、山道年酸、二氢原酸、琥珀酸、噻吩羧酸、四氢叶酸、去氢胆酸、萜烯酸、羟基丙酮羧酸、羟基丙酮二羧酸、羟基苯基乙酸、羟基苯基丙酸、苯二羧酸、尿黑酸、扁桃酸、鼠胆酸、甲基多巴、甲基苯基乙酸、甲基呋喃羧酸、甲基红、甲灭酸、麦角酸、石胆酸、硫辛酸、利血平酸、视黄酸、左旋海松酸、乙醇酸、水杨酸、对酚锌酚醛磺酸盐;植物提取物,诸如药蜀葵(Althea officinalis)、山金车(Arnica montana)、掌参(Polygonum bistorta)、鸢尾属种(Iris)、茴香(Foeniculum vulgare)、大花紫薇(Lagerstroemia speciosa)、甜橙(Citrussinensis)、高粱泡(Rubus L.)、番石榴(Psidium guajava L.)、黑加仑(Ribes nigrum)、童氏老鹳草、野山楂、蚊子草(Filipendula multijuga)、芍药、白桦日本变种(Betulaplatyphylla var.japonica)、忍冬、问荆(Equisetum arvense)、常春藤(Hedera helix)、百里香(Thymus vulgaris)、茶树、欧芹(Petroselinumcrispum)、北美金缕梅(Hamamelisvirginiana)、葡萄属种(Vitis)、矢车菊(Centaurea cyanus)、柠檬(Citrus limon)、紫云英(Astragalus sinicus)、粉花地榆(Sanguisorba officinalis)、金鸡纳树(Cinchonasuccirubra)、鼠尾草(Salvia L.)、南京椴(Tilia miqueliana)、人参(Panax ginseng)[亚洲人参]、欧刺柏(Juniperus communis)、药用迷迭香(Rosmarinus officinalis L.)、小连翘(Hypericum erectum)、银杏(Ginkgo biloba)、香蜂花(Melissa officinalis)、红芒柄花(Ononis spinosa Linn)、七叶树(Aesculus hippocastanum)、日本獐牙菜(Swertiajaponica)、大蒜(Allium sativum)、德国洋甘菊(Matricaria recutita)、百里香(Thymusvulgaris)、薄荷变种(Mentha arvensis var.piperascens)、咬人荨麻(Urticathunbergiana)、辣椒(Capsicum annuum L.)、生姜(Zingiber officinale)、啤酒花(Humulus lupulus)、七叶树、薰衣草(Lavandula angustifolia)、胡萝卜栽培亚种(Daucuscarota subsp.sativus)、芥菜(Brassica juncea)、肉桂(Cinnamomum cassia)B1.、松属(Pinus)、蛇床子(Cnidium officinale Makino)、无梗接骨木(Sambucus sieboldiana)、山芹(Ostericum sieboldii)、日本茛菪(Scopolia japonica)、牡丹(Paeoniasuffruticosa)、杨梅(Myrica rubra)、鱼腥草(Houttuynia cordata)、入骨丹(Nupharjaponicum)、柿属种(Diospyros)、金盏花(Calendula officinalis)、虞美人(Papaverrhoeas L.)、龙胆变种(Gentiana scabra var.buergeri)、珊瑚菜(Glehnia littoralis)、酸橙(Citrus aurantium)、香橙(Citrus junos)、菖蒲(Acorus calamus)、夏蜜柑(Citrusnatsudaidai)、黄香草木樨(Melilotus officinalis)、日本花椒(Zanthoxylumpiperitum)、蓝桉(Eucalyptus globulus)、日本艾蒿变种(Artemisia indicavar.maximowiczii)、蓝萼香茶菜(Rabdosia japonica)、水稻(Oryza sativa)、苦参(Sophora flavescens)、生姜(Zingiber officinale)、丁香(Eugenia caryophyllata)、胡桃(Juglans)叶片、黄芩(Scutellaria baicalensis)、药用鼠尾草(Salvia officinalis)、药用迷迭香(Rosmarinus officinalis L.)、何首乌(Polygonummultiflorum Thunb.)、日本黄连(Coptis japonica(Thunb.)Makino)、黄柏(Phellodendron amurense Rupr.)、黄芩(Scutellaria baicalensis Georgi)、鱼腥草、陈皮(Aurantii nobilis pericarpium)、胡萝卜栽培亚种、灯心草变种(Juncus effusus L.var decipiens Buch)和泽泻(Alismarhizome);白桦的鞣酸和焦油植物提取物;蜂胶、蜂王浆、酵母菌提取物、晚香玉多糖溶液、乌龙茶、明矾、氯化锌、硫酸锌、硫酸铝、氯化铝、氢氧化铝氯化物尿囊素、二羟基铝尿囊素、羟铝基氯化物、氧化锌、硫化锌、磺基碳酸锌、磺基碳酸钠、铝或锆的有机复合物或它们的组合。
在一些实施方案中,该护肤组合物还可包含至少一种缓冲剂。在一些实施方案中,该至少一种缓冲剂可以是柠檬酸、柠檬酸钠、乳酸、乙酸钠、乙醇酸、琥珀酸、乙酸、乙酸钠、乙酸钾、苹果酸、酒石酸、富马酸、磷酸、盐酸、硫酸、硼酸、硼砂、次氮基三乙醇、单乙醇胺、二乙醇胺、三乙醇胺、异丙醇胺、三异丙醇胺、2-氨基-2-甲基-1,3-丙二醇、2-氨基-2-羟甲基-1,3-丙二醇、精氨酸、氢氧化铵、氢氧化钠、氢氧化钾、氢氧化钙、氢氧化镁、氨水中的磷酸氢钾溶液、碳酸胍、碳酸氢铵、碳酸钠、碳酸钾、碳酸氢钾、碳酸氢钠、氧化镁、氧化钙、磷酸铵、磷酸氢二钠、磷酸二氢钠、磷酸钾、磷酸镁、磷酸钙、硼酸钠、偏硼酸钠、柠檬酸钾或它们的组合。
在一些实施方案中,该护肤组合物还可包含至少一种紫外线吸收剂。在一些实施方案中,该至少一种紫外线吸收剂可以是对氨基苯甲酸紫外线吸收剂,诸如对氨基苯甲酸、对氨基苯甲酸单甘油酯、N,N-二丙氧基对氨基苯甲酸乙酯、N,N-二乙氧基对氨基苯甲酸乙酯、N,N-二甲基对氨基苯甲酸乙酯和N,N-二甲基对氨基苯甲酸丁酯;邻氨基苯甲酸紫外线吸收剂,诸如N-乙酰基邻氨基苯甲酸高薄荷基酯;二苯甲酮衍生物,诸如肉桂酸、氧苯酮-3、氧苯酮-4、氧苯酮-5、氧苯酮-9;糖类紫外线吸收剂,其中糖或糖醇与1,3-丙二醇衍生物结合;水杨酸紫外线吸收剂,诸如水杨酸、其钠盐、水杨酸戊酯、水杨酸薄荷酯、水杨酸高薄荷酯、水杨酸辛酯、水杨酸苯酯、水杨酸苄酯、水杨酸对异丙醇苯酯和水杨酸二丙二醇酯;肉桂酸紫外线吸收剂,诸如肉桂酸辛酯、4-异丙基肉桂酸乙酯、2,5-二异丙基肉桂酸甲酯、2,4-二异丙基肉桂酸乙酯、2,4-二异丙基肉桂酸甲酯、对甲氧基肉桂酸丙酯、对甲氧基肉桂酸异丙酯、对甲氧基肉桂酸异戊酯、对甲氧基肉桂酸2-乙基己酯、对甲氧基肉桂酸2-乙氧基乙酯(西诺沙酯(cinoxate))、对甲氧基肉桂酸环己酯、α-氰基-β-苯基肉桂酸乙酯、α-氰基-β-苯基肉桂酸2-乙基己酯(奥克立林(octocrylene))、甘油单-2-乙基己酰基-二对甲氧基肉桂酸酯和阿魏酸及其衍生物;二苯甲酮紫外线吸收剂,诸如2,4-二羟基二苯甲酮、2,2'-二羟基-4-甲氧基二苯甲酮、2,2'-二羟基-4,4'-二甲氧基二苯甲酮、2,2',4,4'-四羟基二苯甲酮、2-羟基-4-甲氧基二苯甲酮、2-羟基-4-甲氧基-4'-甲基二苯甲酮、2-羟基-4-甲氧基二苯甲酮-5-磺酸酯、4-苯基二苯甲酮、2-乙基己基-4'-苯基-二苯甲酮-2-羧酸酯、2-羟基-4-正辛氧基二苯甲酮和4-羟基-3-羧基二苯甲酮;二苯甲酰甲烷衍生物,诸如3-(4'-甲基亚苄基)-d,l-樟脑、3-亚苄基-d,l-樟脑、2-苯基-5-甲基苯并噁唑、2,2'-羟基-5-甲基苯基苯并三唑、2-(2'-羟基-5'-叔辛基苯基)苯并三唑、2-(2'-羟基-5'-甲基苯基)苯并三唑、二苄肼(dibenzalazine)、二茴香酰基甲烷(dianysoylmethane)、5-(3,3-二甲基-2-亚降冰片基)-3-戊-2-酮、4-甲氧基-4'-叔丁基苯甲酰甲烷和4-叔丁基甲氧基二苯甲酰甲烷;尿刊酸紫外线吸收剂,诸如辛基三嗪酮、尿刊酸和尿刊酸乙酯;乙内酰脲衍生物,诸如2-(2'-羟基-5'-甲基苯基)苯并三唑、1-(3,4-二甲氧基苯基)-4,4-二甲基-1,3-戊二酮、二甲氧基亚苄基二氧代咪唑烷丙酸辛酯和二甲氧基亚苄基二氧代咪唑烷丙酸2-乙基己酯;和其他,诸如苯基苯并咪唑磺酸、对苯二亚甲基二樟脑磺酸、甲酚曲唑三硅氧烷、邻氨基苯甲酸甲酯、芸香苷及其衍生物、谷维素及其衍生物、对氨基苯甲酸辛基二甲酯、氧化钛、氧化锌、高岭土、滑石、乙基己基三嗪酮、奥克立林、辛基二甲基PABA、胡莫柳酯、亚甲基双苯并三唑基四甲基丁基苯酚、甲氧基肉桂酸乙基己酯、甲氧基肉桂酸辛酯或它们的组合。
在一些实施方案中,该护肤组合物还可包含至少一种增稠剂。在一些实施方案中,该至少一种增稠剂可以是瓜尔胶、刺槐豆胶、榅桲籽、角叉菜胶、半乳聚糖、阿拉伯树胶、他拉胶、罗望子胶、红藻胶、刺梧桐树胶、黄蜀葵胶、卡拉胶、黄蓍胶、果胶、果胶酸及它们的盐,诸如钠盐;海藻酸及其盐,诸如钠盐;淀粉,诸如甘露聚糖、水稻淀粉、玉米淀粉、马铃薯淀粉和小麦淀粉;糊精、黄原胶、葡聚糖、琥珀酰聚糖、凝胶多糖、透明质酸和它们的盐;黄原胶、普鲁兰多糖、结冷胶、几丁质、壳聚糖、琼脂、褐藻类提取物、硫酸软骨素、酪蛋白、胶原、明胶、白蛋白、甲基纤维素、乙基纤维素、羟丙基纤维素、羟乙基纤维素、羧甲基纤维素以及它们的盐,诸如钠盐;纤维素及其衍生物,诸如甲基羟丙基纤维素、纤维素硫酸钠、二烷基二甲基硫酸铵纤维素、结晶纤维素和纤维素粉末;淀粉高分子,诸如可溶性淀粉、羧甲基淀粉、甲基羟丙基淀粉和甲基淀粉;淀粉衍生物,诸如羟丙基三甲基氯化铵淀粉、玉米淀粉辛烯基琥珀酸铝;藻酸衍生物,诸如藻酸丙二醇酯;两性甲基丙烯酸酯共聚物,诸如聚乙烯吡咯烷酮(PVP)、聚乙烯醇(PVA)、乙烯基吡咯烷酮-乙烯醇共聚物、乙烯醇-乙酸乙烯酯共聚物、聚乙烯基甲基醚、聚乙二醇、聚丙二醇、聚氧乙烯-聚氧丙烯共聚物、(甲基丙烯酰氧乙基羧基甜菜碱/甲基丙烯酸烷基酯)共聚物、丙烯酸酯/丙烯酸硬脂酯/氧化乙胺甲基丙烯酸酯共聚物;二甲硅油/乙烯基二甲聚硅氧烷交联聚合物、(丙烯酸烷基酯/双丙酮丙烯酰胺)共聚物、(丙烯酸烷基酯/双丙酮丙烯酰胺)共聚物AMP、部分皂化的聚乙酸乙烯酯、马来酸共聚物、聚乙烯吡咯烷酮、乙烯基吡咯烷酮-甲基丙烯酸二烷基氨基烷基酯共聚物;链烷醇胺丙烯酸树脂;聚酯;水分散性聚酯;聚丙烯酰胺;聚丙烯酸酯共聚物,诸如聚丙烯酸乙酯;羧基乙烯基聚合物;聚丙烯酸,包括其盐,诸如钠盐;丙烯酸/甲基丙烯酸共聚物;丙烯酸/甲基丙烯酸烷基共聚物;阳离子化纤维素,诸如聚季铵盐-10;二烯丙基二甲基氯化铵/丙烯酰胺共聚物,诸如聚季铵盐-7等;丙烯酸/二烯丙基二甲基氯化铵共聚物,诸如聚季铵盐-22;丙烯酸/二烯丙基二甲基氯化铵/丙烯酰胺共聚物,诸如聚季铵盐-39;丙烯酸/阳离子化甲基丙烯酸酯共聚物;丙烯酸/阳离子化甲基丙烯酰胺共聚物;丙烯酸/丙烯酸甲酯/甲基丙烯酰胺丙基三甲基-氯化铵共聚物,诸如聚季铵盐-47;氯化甲基丙烯酸胆碱酯共聚物;阳离子化多糖,诸如阳离子化寡糖、阳离子化葡聚糖和瓜尔胶羟丙基三甲基氯化铵;聚乙烯亚胺;阳离子聚合物;2-甲基丙烯酰氧基乙基磷酰胆碱共聚物,诸如聚季铵盐-51;高分子乳液,诸如丙烯酸类树脂乳液、聚丙烯酸乙基乳液、聚丙烯酸烷基酯乳液、聚乙酸乙烯酯树脂乳液、天然橡胶乳胶和合成乳胶;硝酸纤维素、聚氨酯及其共聚物;硅共聚物,诸如硅、丙烯酰基/硅接枝共聚物;氟高分子;12-羟基硬脂酸及其盐;糊精脂肪酸酯,诸如糊精棕榈酸酯和糊精肉豆蔻酸酯;羟基硬脂酸胆固醇;硅酸酐;煅制二氧化硅(超细硅酸酐);硅酸铝镁;硅酸钠镁;金属皂;二烷基磷酸金属盐;膨润土;锂蒙脱石;亲有机性粘土矿物;蔗糖脂肪酸酯;低聚果糖脂肪酸酯;榅桲籽提取物;以及天然的、半合成的和合成的高分子物质,诸如羟乙基瓜尔胶、羧甲基瓜尔胶、淀粉、羧甲基壳聚糖或它们的组合。
在一些实施方案中,该组合物可包含至少一种氨基酸。在一些实施方案中,该至少一种氨基酸可以是丙氨酸、亮氨酸、异亮氨酸、苏氨酸、甲硫氨酸、苯丙氨酸、色氨酸、赖氨酸、甘氨酸、丙氨酸、天冬酰胺、谷氨酰胺、丝氨酸、半胱氨酸、胱氨酸、酪氨酸、脯氨酸、羟基脯氨酸、天冬氨酸、谷氨酸、羟赖氨酸、精氨酸、鸟氨酸、组氨酸、牛磺酸、肉碱和它们的硫酸盐、磷酸盐、硝酸盐、柠檬酸盐、吡咯烷酮羧酸盐和它们的衍生物,或它们的组合。
在一些实施方案中,该组合物可包含至少一种经皮吸收加速剂。在一些实施方案中,该至少一种经皮吸收加速剂可以是尿素;α-羟酸,诸如乳酸、果酸和乙醇酸;β-羟酸,诸如水杨酸;和其他,诸如油酸、十一烷酸、辛醇、壬醇、薄荷醇、麝香草酚、柠檬烯、二甲基亚砜、月桂基甲基亚砜、二甲基乙酰胺、N,N-二甲基甲酰胺、月桂基硫酸钠、N,N-双(2-羟乙基)油胺、聚氧乙烯(20)脱水山梨糖醇单油酸酯、十二烷基二甲基铵丙磺酸、丙二醇、聚乙二醇、N,N-二甲基-间甲苯酰胺、N,N-二乙基-间甲苯酰胺、月桂氮卓酮、1-十二烷基氮杂环庚烷-2-酮、肉豆蔻酸异丙酯、棕榈酸异丙酯、N-单取代或二取代的对薄荷烷-3-甲酰胺、2-(2-甲氧基-1-甲基乙基)-5-甲基环己醇、氮杂环烷衍生物、环糊精或它们的组合。
在一些实施方案中,该护肤组合物还可包含至少一种发泡剂。在一些实施方案中,该至少一种发泡剂可以是偶氮二甲酰胺、偶氮二羧酸钡、偶氮二异丁腈、偶氮二碳酸酰胺、N,N'-二亚硝基五亚甲基四胺、N,N'-二甲基-N,N'-二亚硝基对苯二甲酰胺、三亚硝基三甲基三胺、4,4'-氧双(苯磺酰肼)、对甲苯磺酰肼、二苯基砜-3,3'-磺酰肼、芳基双(磺酰肼)、对甲苯磺酰氨基脲和4,4'-氧双(苯磺酰氨基脲);氟烷烃,诸如三氯氟甲烷和二氯一氟甲烷;5-吗啡基-1,2,3,4-硫杂三唑、碳酸铵、碳酸氢铵、碳酸氢钠、亚硝酸铵、硼氢化钠、叠氮化物或它们的组合。
在一些实施方案中,组合物可包含至少一种增塑剂。在一些实施方案中,该至少一种增塑剂可以是乙醇、苯氧乙醇、异丙醇、丁醇、苄醇、月桂醇、肉豆蔻醇、鲸蜡醇、鲸蜡硬脂醇、硬脂醇、油醇、山嵛醇;多元醇,诸如乙二醇、二乙二醇、三乙二醇、聚乙二醇、丙二醇、二丙二醇、聚丙二醇、甘油、二甘油、聚甘油、单硬脂酸甘油酯、异丙二醇、1,2-丁二醇、1,3-丁二醇、1,4-丁二醇、2,3-丁二醇、1,2-戊二醇、1,5-戊二醇、2,3-戊二醇、2,4-戊二醇、山梨糖醇、麦芽糖醇、棉子糖、己二醇、月桂酸二乙醇酰胺、脂肪酸二乙醇酰胺或它们的组合。
皂
在一些实施方案中,本文所述的组合物可以是清洁组合物或皂,包括固体棒形式的传统皂及清洁剂、卸妆液、沐浴露、乳液、乳霜、泡沫乳霜凝胶或者可包装在管、瓶、泵瓶、气溶胶淋浴泡沫或泡沫泵瓶中的凝胶形式的液体皂。皂可用于美容方法中在水的存在下清洁人角质材料的污垢残余物,聚集形成泡沫,并且所形成的泡沫和污物残余物通过用水冲洗而去除,并且可用于本文公开的身体和面部的任何部分,包括例如身体皮肤、面部、手、嘴唇、眼睑、指甲、毛发、睫毛和/或眉毛上。
传统上,固体皂包括碱金属脂肪酸盐和脂肪酸钾皂,并且液体皂包括四个主要家族的洗涤剂调配物:(1)基于月桂基硫酸盐的洗涤剂调配物;基于α-烯烃磺酸盐的洗涤剂调配物;(3)基于合成的阴离子表面活性剂、两性表面活性剂和/或非离子表面活性剂的混合物的洗涤剂调配物;(4)基于皂和合成表面活性剂的混合调配物。液体皂通常含有增稠体系,该增稠体系选自例如电解质诸如氯化钠、氯化钾或硫酸钾;烷醇酰胺诸如椰油酰胺DEA或椰油酰胺MEA;聚乙二醇与一元酸或硬脂酸的酯,诸如聚乙二醇二硬脂酸酯6000或其混合物,并且液体皂包含在美容上可接受的水性介质中。然而,固体皂和液体皂都可以以任何组合包含任何合适的附加成分,诸如下文列出的那些成分。
在一些实施方案中,本文所述的清洁组合物或皂还可包含:一种或多种纤维素化合物,或在其结构中具有通过β-1,4键连接的葡萄糖残基链的多糖化合物;一种或多种包含具有6至30个碳原子或12至22个碳原子的直链或支链、饱和或不饱和烷基链的脂肪酸;一种或多种脂肪酸,包括月桂酸、肉豆蔻酸、棕榈酸和硬脂酸、亚麻酸及它们的混合物;以及一种或多种无机碱,包括碱金属氢氧化物(氢氧化钠和钾氢氧化物)、金属氢氧化物或氨,或有机碱,诸如三乙醇胺、单乙醇胺、单异丙醇胺、N-甲基葡糖胺、赖氨酸和精氨酸。
在一些实施方案中,本文所述的组合物还可包含一种或多种阴离子表面活性剂或盐,包括碱金属盐诸如钠盐、铵盐、胺盐、氨基醇盐或以下类型的碱土金属(例如镁)的盐:烷基硫酸盐、烷基醚硫酸盐、烷基酰氨基醚硫酸盐、烷基芳基聚醚硫酸盐、单甘油酯硫酸盐;烷基磺酸盐、烷基酰胺磺酸盐、烷基芳基磺酸盐、α-烯烃-磺酸盐、石蜡-磺酸盐;烷基磺基琥珀酸盐、烷基醚磺基琥珀酸盐、烷基酰胺磺基琥珀酸盐;烷基磺基乙酸盐;酰基肌氨酸盐;和酰基谷氨酸盐,所有这些化合物的烷基和酰基都具有6至24个碳原子并且芳基表示苯基或苄基;聚糖苷羧酸的C6-C24烷基酯,诸如柠檬酸烷基葡糖苷酯、酒石酸烷基聚糖苷酯和磺基琥珀酸烷基聚糖苷酯、磺基琥珀酸烷基酯、酰基羟乙基磺酸酯和N-酰基牛磺酸酯,所有这些化合物的烷基或酰基都具有12至20个碳原子;和/或酰基含有8至20个碳原子的酰基乳酸酯和它们的混合物。在一些实施方案中,烷基-D-半乳糖苷糖醛酸、聚氧亚烷基化(C6-C24)醚羧酸、聚氧亚烷基化(C6-C24)芳基(C6-C24)聚氧亚烷基化醚羧酸、聚氧亚烷基化(C6-C24)烷基酰氨基醚羧酸,尤其是含有2至50个环氧乙烷基团的那些;以及它们的碱金属盐、铵盐、胺盐、氨基醇盐或碱土金属盐也可以是合适的。
含有1至30个环氧乙烷基团的合适的C6-C24烷基醚硫酸盐包括碱金属盐或碱土金属盐、铵盐、胺盐或氨基醇盐、钠盐和氧乙烯化(C12-C14)烷基醚硫酸盐,其环氧乙烷基团的平均数为1至4并且包括月桂醇聚醚硫酸钠(CTFA名称),诸如以名称TEXAPON AOS225UPTEXAPON N702TEXAPON NSW销售的由COGNIS生产上市的商品或以EMPICOL ESB3/FL2、EMPICOL ESB3/FL3、EMPICOL ESB70/FL2由Huntsman公司销售的商品。
合适的两性表面活性剂包括但不限于脂族仲胺或脂族叔胺的衍生物,其中脂族基团是包含8至22个碳原子的直链或支链。两性表面活性剂可含有至少一个水溶性阴离子基团,诸如羧酸根、磺酸根、硫酸根、磷酸根或膦酸根基团、(C8-C20)烷基甜菜碱、磺基甜菜碱、(C8-C20)烷基酰氨基(C6-C8)烷基甜菜碱或(C8-C20)烷基酰氨基烷基(C6-C8)磺基甜菜碱及它们的混合物。
合适的胺衍生物包括以名称销售的产品,如美国专利第2,528,378号和美国专利第2,781,354号中所述并且在CTFA词典1982年第3版中以术语两性羧基甘氨酸盐和两性羧基丙酸盐命名提交。其他合适的胺衍生物包括由Rhodia浓缩的以商品名C2M销售的,在CTFA词典1993年第5版中分类在以下名称下的那些胺衍生物:椰油酰两性基二乙酸二钠盐、月桂酰两性基二乙酸二钠盐、癸酰两性基二乙酸二钠盐、辛酰两性基二乙酸二钠盐、椰油酰两性基二丙酸二钠盐、月桂酰两性基二丙酸二钠盐、癸酰两性基二丙酸二钠盐、辛酰两性基二丙酸二钠盐、月桂酰两性基二丙酸、椰油酰两性基二丙酸和椰油酰两性基二乙酸盐。合适的烷基(C8-C20)甜菜碱包括椰油酰氨基丙基甜菜碱和椰油基甜菜碱,诸如来自RHODIA的商品MIRATAINE BB/FLA或来自Huntsman的商品EMPIGEN BB/FL。
在一些实施方案中,本文所述的清洁组合物或皂可不含硫酸盐,并且可包括不含硫酸盐的表面活性剂体系。
在一些实施方案中,本文所述的清洁组合物或皂还可包含一种或多种非离子纤维素化合物类型的增稠剂。合适的纤维素化合物包括但不限于非离子纤维素醚,包括甲基纤维素和乙基纤维素;羟烷基纤维素,诸如羟甲基纤维素、羟乙基纤维素和羟丙基纤维素;混合羟烷基-烷基纤维素纤维素,诸如羟丙基-甲基纤维素、羟乙基-甲基纤维素、羟乙基乙基纤维素和羟丁基-甲基纤维素以及经烷基链改性的羟烷基纤维素。合适的羟丙基甲基纤维素包括由Dow Coming销售的商品METHOCEL E、F、J和K,甚至更特别地METHOCEL E 4MQG或METHOCEL F 4M。合适的纤维素成分可以是结晶形式、微晶形式或它们的混合物。
在一些实施方案中,本文所述的清洁组合物或皂还可包含一种或多种另外的增稠剂,包括电解质诸如氯化钠、氯化钾或硫酸钾;烷醇酰胺诸如椰油酰胺DEA或椰油酰胺MEA;聚乙二醇和一元酸或硬脂酸的酯诸如聚乙二醇二硬脂酸酯6000或其混合物;多糖生物聚合物诸如黄原胶、瓜尔胶、藻酸盐;合成聚合物,诸如聚丙烯酸类诸如NOVEON生产上市的CARBOPOL 980、CARBOPOL 1382,丙烯酸酯/丙烯腈共聚物诸如KINGSTON生产上市的HYPANSS201;粘土诸如绿土,改性或未改性的锂蒙脱石诸如Rheox生产上市的BENTONE产品,Southern Clay Products生产上市的LAPONITE产品,RT Vanderbilt生产上市的VEEGUM HS产品,及它们的混合物。
在一些实施方案中,本文所述的清洁组合物或皂还可包含一种或多种非离子表面活性剂。这些是公知的化合物(参见MR Porter的“Handbook of Surfactants”,Blackie&Son编辑(Glasgow and London),1991,第116-178页),并且可选自醇、α-二醇、(C1-C20)烷基酚或聚乙氧基化脂肪酸、聚丙氧基化脂肪酸或聚甘油化脂肪酸,这些脂肪酸具有包含例如8至18个原子的脂肪链,环氧乙烷基团或环氧丙烷的数目可在2至50的范围内并且甘油基团的数目可在2至30的范围内;环氧乙烷和丙烯的共聚物;脂肪醇上环氧乙烷和环氧丙烷的缩合物;具有2至30摩尔环氧乙烷的聚乙氧基化脂肪酰胺、平均包含1至5个甘油基团的聚甘油化脂肪酰胺;具有2至30摩尔环氧乙烷的聚乙氧基化脂肪胺、具有2至30摩尔环氧乙烷的乙氧基化脱水山梨糖醇脂肪酸酯;蔗糖脂肪酸酯、聚乙二醇脂肪酸酯、(C6-C24)烷基多糖苷、N-烷基(C6-C24)葡糖胺衍生物、氧化胺,诸如烷基(C10-C14)胺的氧化物或N-酰基(C10-C14)-氨基丙基吗啉的氧化物,及它们的混合物。
其他合适的非离子表面活性剂包括但不限于烷基多葡糖苷(APG)、麦芽糖酯、聚甘油化脂肪醇、葡糖胺衍生物(例如2-乙基己氧基羰基-N-甲基葡糖胺)及它们的混合物。合适的烷基多葡糖苷包括含有包含6至30个碳原子的烷基和亲水基团(葡糖苷)的那些烷基多葡糖苷。示例性烷基多葡糖苷包括癸基葡糖苷(烷基-C9/C11-多葡糖苷(1.4)),包括由KaoChemicals公司以名称Mydol销售的产品,由Cognis公司以名称Plantaren 2000/>销售的产品和由SEPPIC公司以名称Oramix NS/>销售的产品;以及辛基/癸基葡糖苷,包括由SEPPIC公司以名称Oramix CG/>销售的产品;由Cognis公司以Plantaren 1200/>和Plantacare/>销售的月桂基葡糖苷,以及椰油基葡糖苷,例如由Cognis公司以名称Plantacare 818//>销售的产品。
合适的麦芽糖衍生物包括文件EP-A-566 438中描述的那些,诸如文件FR-2 739556中描述的0-辛酰基-6'-D-麦芽糖或O-十二酰基-6'-D-麦芽糖。
在一些实施方案中,该清洁组合物或皂可配制在美容上可接受的水性介质中。除了水以外,合适的美容上可接受的水性介质还可包括一种或多种溶剂,诸如含有1至6个碳原子的低级醇,诸如乙醇;多元醇,诸如甘油;二醇,诸如丁二醇、异戊二醇、丙二醇、聚乙二醇(诸如PEG-8)、山梨醇;糖,诸如葡萄糖、果糖、麦芽糖、乳糖、蔗糖,以及它们的混合物。本文所公开的组合物中溶剂的量可以为0.1重量%至95重量%。
在一些实施方案中,本文所述的清洁组合物或皂还可包含一种或多种聚季铵盐类型的阳离子聚合物,该阳离子聚合物可为发泡组合物提供柔软性和润滑性。合适的阳离子聚合物包括聚季铵盐5诸如CALGON公司生产上市的产品MERQUAT 5,聚季铵盐6诸如CIBA公司生产上市的产品SALCARE SC 30和CALGON公司生产上市的产品MERQUAT 100,聚季铵盐7诸如CALGON公司生产上市的产品MERQUAT S、MERQUAT 2200和MERQUAT 550以及CIBA公司生产上市的产品SALCARE SC 10,聚季铵盐10诸如Amerchol公司生产上市的产品PolymerJR400,聚季铵盐11诸如ISP生产上市的产品GAFQUAT 755、GAFQUAT 755N和GAFQUAT 734,聚季铵盐15诸如ROHM公司生产上市的产品ROHAGIT KF 720F,聚季铵盐16诸如BASF生产上市的产品LUVIQUAT FC905、LUVIQUAT FC370、LUVIQUAT HM552和LUVIQUAT FC550,聚季铵盐22诸如Calgon公司生产上市的产品Merquat 280,聚季铵盐28诸如ISP公司生产上市的产品STYLEZE CC10,聚季铵盐39诸如Calgon生产上市的产品MERQUAT PLUS 3330,聚季铵盐44诸如BASF销售的产品LUVIQUAT CARE,聚季铵盐46诸如BASF公司生产上市的产品LUVIQUATHOLD,聚季铵盐47诸如Calgon生产上市的产品MERQUAT 2001,以及阳离子瓜尔胶诸如Rhodia公司生产上市的产品Jaguar也可作为阳离子聚合物使用。
在一些实施方案中,本文所述的清洁组合物或皂还可包含用于美容组合物中的一种或多种助剂或添加剂。合适的佐剂或添加剂包括但不限于:油、活性剂、香料、防腐剂、螯合剂、珠光剂或防晒剂、颜料、珠光剂、无机填充剂或有机填充剂诸如滑石、高岭土、二氧化硅粉末或聚乙烯、可溶性染料或它们的任何组合。
油的示例包括植物油(荷荷巴油、鳄梨油、芝麻油、葵花油、玉米油、大豆油、红花油、葡萄籽油)、矿物油(凡士林、任选氢化的异链烷烃)、合成油(肉豆蔻酸异丙酯、辛酸鲸蜡硬脂醇酯、聚异丁烯、棕榈酸乙基己基酯、苯甲酸烷基酯)、挥发性或非挥发性硅酮油诸如聚二甲基硅氧烷(PDMS)和环二甲基硅氧烷或环甲硅油,以及氟化或氟硅酮油及它们的混合物。
示例性的活性剂包括防晒剂、脱屑剂、增湿剂、脱色剂、促染色剂、α-羟酸、抗菌剂、抗自由基剂、抗污剂、抗炎剂、类视黄醇,藻类、蘑菇、蔬菜、酵母、细菌的提取物,水解蛋白、部分水解蛋白或未水解蛋白、酶、激素、维生素及它们的衍生物、类黄酮和异黄酮,以及它们的混合物。
根据所选择的应用,本文所述的清洁组合物或皂可具有6至10范围内的pH。常规地可通过在组合物中添加碱(有机碱或无机碱),例如氨或伯、仲或叔(聚)胺,诸如单乙醇胺、二乙醇胺、三乙醇胺、异丙醇胺或1,3-丙二胺,或通过添加无机酸或有机酸,诸如羧酸,例如柠檬酸,将pH调节到所需值。在淋浴凝胶的情况下,pH可以从8至10变化。
在一些实施方案中,本文所述的清洁组合物还可包含任选的添加剂,诸如着色剂、香味剂、抗菌剂、防腐剂、抗氧化剂、珠粒(香味、去角质或增湿珠粒)、云母、闪光剂、乳木果油、乳木果油珠粒、遮光剂、珠光剂和其他此类成分。在一些实施方案中,该组合物具有高透明度(约2NTU至约25NTU)、约1/4至约1/8范围的易于从孔口分配的目标粘度(约4,000厘泊至约10,000厘泊)以及允许组合物以均匀分布和增强的稳定性(例如,在120℉(49℃)下约8个月)悬浮多种添加剂的屈服值(约3帕斯卡至约15帕斯卡)以及它们的任何混合。
在一些实施方案中,该清洁组合物或皂还可包含一种或多种增湿剂/润肤剂。增湿剂可包含在条形或液体皂组合物中以向皮肤提供调理益处。术语“增湿剂”描述赋予皮肤表面光滑和柔软感觉的材料。
存在两种减少水从角质层损失的方式。一种是在皮肤表面上沉积降低蒸发速率的闭塞层。第二种方法是将非闭塞性吸湿性物质添加到角质层,该非闭塞性吸湿性物质将保留水,并且使该水可用于角质层以改变其物理性质并产生美容上期望的效果。非闭塞性增湿剂还通过改善皮肤的润滑性而起作用。
闭塞性增湿剂和非闭塞性增湿剂均考虑用于本文所述的组合物中。示例性增湿剂包括长链脂肪酸、液体水溶性多元醇、甘油、丙二醇、山梨醇、聚乙二醇、甲基葡萄糖的乙氧基化/丙氧基化醚(例如,甲基葡糖醇聚醚-20)、羊毛脂醇的乙氧基化/丙氧基化醚(例如,可从Amerchol Co.获得的)、椰子和牛油脂肪酸、液体水溶性多元醇(例如,甘油、丙二醇、丁二醇、己二醇、聚丙二和聚乙二醇)。
非闭塞性增湿剂可天然存在于皮肤的角质层中,诸如吡咯烷酮羧酸钠、乳酸、尿素、L-脯氨酸、胍和吡咯烷酮。其他非闭塞性增湿剂的示例包括己二酸、乳酸、油酸、硬脂酸、异硬脂酸、肉豆蔻酸或亚油酸的十六烷基酯、肉豆蔻基酯、异癸基或异丙酯,以及许多它们相应的醇酯(异硬脂酰-2-乳酸钠、辛基乳酸钠)、水解蛋白和其他胶原衍生蛋白、芦荟凝胶和乙酰胺MEA(N-乙酰基乙醇胺)。闭塞和非闭塞类型的增湿剂的其他示例公开于以引用方式并入本文的1981年5月J.Mausner的“Emollients--ACritical Evaluation”,Cosmetics&Toiletries中。
示例性的闭塞性增湿剂包括矿脂、矿物油、蜂蜡、硅酮、羊毛脂和油溶性羊毛脂衍生物、饱和和不饱和脂肪醇诸如山嵛醇、角鲨烯和角鲨烷,以及各种动物油和植物油诸如杏仁油、花生油、小麦胚芽油、亚麻子油、荷荷巴油、杏核油、胡桃油、棕榈坚果油、开心果油、芝麻油、菜籽油、杜松油、玉米油、桃核油、罂粟籽油、松油、蓖麻油、大豆油、鳄梨油、葵花油、椰油、榛果油、橄榄油、葡萄籽油和葵花籽油。
毛发护理
在一些实施方案中,该组合物可以是包含通常用于毛发护理产品的成分的毛发护理组合物。这些成分可包括但不限于清洁剂、起泡剂、水合剂、表面活性剂、洗涤剂、胶凝剂、香味剂、植物提取物、调理剂、保湿剂、硅酮或硅酮衍生物、增稠试剂、防晒剂、维生素、醇、多元醇、多元醇醚及洗发剂、调理剂和定型剂中的其他常用成分。毛发护理产品通常包括一种或多种表面活性剂、一种或多种粘度调节剂、一种或多种防腐剂和一种或多种香味剂,以及下面列出的任何成分或它们的组合。
通常,毛发可通过外部大气因素诸如光和恶劣天气的作用,以及通过机械或化学处理诸如刷、梳理、染色、漂白、烫发和/或松弛而受损和变脆,并且随着时间的推移,毛发可变得干燥、粗糙、暗淡和/或脆弱。为了克服这些缺点,通常的做法是使用适当地调理毛发的护理组合物,从而赋予其令人满意的美容特性,尤其是在光滑度、光泽、柔软性、柔韧性、亮度、自然感和良好的解缠结特性方面。这些毛发护理组合物可以是,例如,洗发剂、调理洗发剂、毛发调理剂、发膜、精华液、凝胶、洗发液和乳膏,它们可以被冲洗掉或留在组合物中。在各种实施方案中,这些组合物通常包含阳离子调理剂诸如阳离子表面活性剂、阳离子聚合物、硅酮和/或脂肪物质诸如脂肪醇的组合,以便给予毛发在柔软性、光滑度和柔韧性方面令人满意的特性。示例性组合物可包含硅酮,已知硅酮在光滑度和柔性方面改善毛发的美容特性(如美国专利第5,374,421号中所示,各自以引用方式并入本文)。
在一些实施方案中,该毛发护理组合物还可包含一种或多种非氨基聚烷基硅氧烷、在脂肪醇的存在下的一种或多种氧乙烯化聚合物、包含至少一条具有至少12个碳原子的烷基链的一种或多种非氨基聚烷基硅氧烷、一种或多种氧乙烯化聚合物和/或一种或多种脂肪醇。示例性的氧乙烯化聚合物可具有大于或等于106的重均分子量。在一些实施方案中,氧乙烯化聚合物可以选自具有式H(OCH2CH2)zOH的化合物,其中z是大于或等于30,000的整数。在某些实施方案中,z的范围可以为30,000至120,000,或40,000至95,000。在一些实施方案中,氧乙烯化聚合物可以是PEG-45M(z=45,000),诸如由Amerchol公司以名称Polyox WSR N 60K销售的产品,和PEG-90M(z=90 000),及它们的混合物。
在一些实施方案中,该毛发护理组合物还可包含一种或多种脂肪醇。术语“脂肪醇”意指包含至少8个碳原子并且未被氧亚烷基化的任何饱和或不饱和的直链或支链醇。示例性的脂肪醇在室温(25℃)和大气压(1.013*105Pa)下为固体。示例性的脂肪醇包括鲸蜡醇、硬脂醇、油醇、山嵛醇、亚油醇、棕榈油醇、花生四烯醇、瓢儿菜醇、鲸蜡硬脂基醇(或鲸蜡硬脂醇)以及它们的混合物。
在一些实施方案中,该毛发护理组合物还可包含一种或多种调理剂,包括阳离子表面活性剂、阳离子聚合物以及它们的混合物。术语“阳离子表面活性剂”意指当包含在本文所述的组合物中时带正电荷的表面活性剂。合适的阳离子表面活性剂可选自任选聚氧亚烷基化的伯脂肪胺、仲脂肪胺或叔脂肪胺或它们的盐和季铵盐,以及它们的混合物。示例性的脂肪胺是硬脂酰胺丙基二甲基胺。示例性的季铵盐包括四烷基铵盐,包括其中烷基含有大约16至22个碳原子的二烷基二甲基铵盐或烷基三甲基铵盐,尤其是山嵛基三甲基铵、二硬脂基二甲基铵、鲸蜡基三甲基铵或苄基二甲基硬脂基铵盐,或者另一方面,包括由VanDyk公司以名称CERAPHYL 70销售的棕榈酰胺丙基三甲基铵盐、硬脂酰胺丙基三甲基铵盐、硬脂酰胺丙基二甲基鲸蜡硬脂基铵盐或硬脂酰胺丙基二甲基(肉豆蔻基乙酸)铵盐。
术语“阳离子聚合物”意指含有阳离子基团和/或可离子化为阳离子基团的基团的任何聚合物,该聚合物可以是非含硅的。示例性的阳离子聚合物包括任何已知用于对毛发进行定型的聚合物,例如在专利申请EP-A-0337 354和法国专利申请FR-A-2 270 846、2383 660、2 598 611、2 470 596和2 519 863中描述的那些聚合物,每个专利申请都以引用方式整体并入。另外的示例性阳离子聚合物包括含有包含伯胺、仲胺、叔胺和/或季胺基团的单元的那些阳离子聚合物,该单元可以形成聚合物主链的一部分或者可以由直接与之连接的侧取代基携带。合适的阳离子聚合物可具有大于105的重均分子量,包括聚胺、聚氨基酰胺和聚季铵类型的聚合物,包括法国专利2 505 348和2 542 997中描述的那些聚合物,每个专利以引用方式整体并入本文。
在一些实施方案中,该毛发护理组合物还可包含“非硫酸盐”清洁剂、起泡剂或表面活性剂。合适的“非硫酸盐”试剂包括但不限于:月桂酰甲基羟乙基磺酸钠丙二醇、甲基油酰牛磺酸钠和椰油基羟乙基磺酸钠。
在一些实施方案中,该毛发护理组合物还可包含以下任何成分或它们的混合物:由油菜籽合成得到的季铵化合物、乙烯基吡咯烷酮和/或乙烯基咪唑的季铵聚合物,例如由BASF公司以名称LUVIQUAT FC 905、FC 550和FC 370及LUVIQUAT Excellence销售的产品;阳离子多糖,包括阳离子纤维素,包括包含季铵基团的纤维素醚衍生物,阳离子纤维素共聚物或用水溶性季铵单体接枝的纤维素衍生物,和阳离子半乳甘露聚糖胶。包含季铵基团的示例性纤维素醚衍生物在法国专利1 492 597中有描述。这些聚合物在CTFA词典中也被定义为已经与被三甲基铵基取代的环氧化物反应的羟乙基纤维素的季铵。阳离子纤维素共聚物或用水溶性季铵单体接枝的纤维素衍生物在美国专利第4,131,576号中有描述,诸如尤其用甲基丙烯酰基乙基三甲基铵、甲基丙烯酰胺丙基三甲基铵或二甲基二烯丙基铵盐接枝的羟烷基纤维素,例如羟甲基纤维素、羟乙基纤维素或羟丙基纤维素。合适的相关纤维素诸如用C8-C30脂肪链季铵化的烷基羟乙基纤维素,诸如由Amerchol/Dow Chemical公司销售的产品QUATRISOFT LM 200(INCI名称聚季铵盐-24)和由Croda公司销售的产品CRODACELQM(INCI名称PG-羟乙基纤维素椰油二甲基氯化铵)、CRODACEL QL(C12烷基)(INCI名称PG-羟乙基纤维素月桂基二甲基氯化铵)和CRODACEL QS(C18烷基)(INCI名称PG-羟乙基纤维素硬脂基二甲基氯化铵)。其他合适的脂肪链羟乙基纤维素衍生物包括来自Amerchol/Dowchemical公司的商品SOFTCAT Polymer SL,诸如INCI名称为聚季铵盐-67的SL-100、SL-60、SL-30和SL-5。合适的阳离子半乳甘露聚糖胶在美国专利第3,589,578号和第4 031 307号中有描述。合适的纤维素成分可以是结晶形式、微晶形式或它们的混合物。
在一些实施方案中,该毛发护理组合物还可包含一种或多种阳离子蛋白或阳离子蛋白水解产物、聚亚烷基亚胺(包括聚乙烯亚胺)、含有乙烯基吡啶或乙烯基吡啶鎓单元的聚合物、聚胺和表氯醇缩合物、季多亚脲和几丁质衍生物、带有三甲基苄基铵基团的动物蛋白水解产物(诸如由Croda公司以名称Crotein BTA销售且在CTFA词典中称为苄基三甲基铵水解动物蛋白的产品)、在多肽链上带有季铵基团的蛋白水解产物,所述铵基团包含至少一个具有1至18个碳原子的烷基。
在一些实施方案中,该毛发护理组合物还可包含一种或多种季铵化植物蛋白,诸如来自小麦蛋白、玉米蛋白或大豆蛋白的季铵化植物蛋白,例如季铵化小麦蛋白,包括由Croda公司以名称Hydrotriticum WQ或QM销售的在CTFA词典中称为椰油二甲基铵水解小麦蛋白,以名称Hydrotriticum QL销售的在CTFA词典中称为月桂二甲基铵水解小麦蛋白,或其他以名称Hydrotriticum QS销售的在CTFA词典中称为硬脂基二甲基铵水解小麦蛋白的那些。
在一些实施方案中,该毛发护理组合物还可包含一种或多种聚胺,诸如由Cognis销售的,在CTFA词典中以名称聚乙二醇牛脂基聚胺提及的POLYQUART R H。其他合适的聚合物包括BASF公司以名称Lupamin销售的那些聚合物,以及以名称Lupamin 9095、Lupamin5095、Lupamin1095、Lupamin 9030和Lupamin 9010销售的产品。
在一些实施方案中,该毛发护理组合物还可包含一种或多种在室温(25℃)和大气压(1.013*105Pa)下为液体的脂肪物质。术语“脂肪物质”意指在常温(25℃)和大气压(1.013*105Pa)下不溶于水的有机化合物(溶解度小于5%、小于1%或小于0.1%)。脂肪物质通常在相同的温度和压力条件下可溶于有机溶剂中,例如可溶于氯仿、二氯甲烷、四氯化碳、乙醇、苯、甲苯、四氢呋喃(THF)、液体矿脂或十甲基环五硅氧烷中。本公开的液体脂肪物质可以是非聚氧乙烯化的和非聚甘油化的。术语“油”意指在室温(25℃)和大气压(1.013*105Pa)下为液体的“脂肪物质”。术语“非硅酮油”意指不含任何硅原子(Si)的油并且术语“硅酮油”意指含有至少一个硅原子的油。液体脂肪物质可以选自非硅酮油,诸如尤其是C6-C16液烃、含有多于16个碳原子的液烃、动物来源的非硅酮油、植物来源或合成来源的甘油三酯、氟油、除甘油三酯之外的液体脂肪酸和/或脂肪醇酯以及它们的混合物。液烃可以是直链、支链或任选环状的,包括己烷、环己烷、十一烷、十二烷、十三烷或异链烷烃,诸如异十六烷、异癸烷或异十二烷,以及它们的混合物。含有多于16个碳原子的矿物来源或合成来源的合适的直链或支链液烃可以选自液体石蜡、矿脂、液体矿脂、矿物油、聚癸烯和氢化聚异丁烯(诸如PARLEAM)及它们的混合物。可以使用动物来源的烃基油,诸如全氢化角鲨烯。
示例性的植物来源或合成来源的甘油三酯可选自包含6至30个碳原子的液体脂肪酸甘油三酯,例如庚酸或辛酸甘油三酯,或者可替代地,更特别地选自存在于植物油,例如椰油、葵花油、玉米油、大豆油、髓油、葡萄籽油、芝麻油、榛果油、杏仁油、澳洲坚果油、阿拉拉油(arara oil)、蓖麻油、鳄梨油、荷荷巴油、乳木果油中的那些甘油三酯,或合成的辛酸/癸酸甘油三酯,诸如由Stearineries Dubois公司销售的那些甘油三酯或由Dynamit Nobel公司以名称MIGLYOL 810、812和818销售的那些甘油三酯,及它们的混合物。合适的氟油包括全氟甲基环戊烷和全氟-1,3-二甲基环己烷,诸如BNFL Fluorochemicals公司的FLUTESCPC1和FLUTESC PC3;全氟-1,2-二甲基环丁烷;全氟烷烃,诸如由3M公司以名称PF 5050和PF5060销售的十二氟戊烷和十四氟己烷,或由Atochem公司以名称FORALKYL销售的溴全氟辛烷;九氟甲氧基丁烷和九氟乙氧基异丁烷;全氟吗啉衍生物,诸如由3M公司以名称PF 5052销售的4-三氟甲基全氟吗啉。
合适的单酯包括二氢枞醇山嵛酸酯;辛基十二醇山嵛酸酯;异鲸蜡醇山嵛酸酯;鲸蜡基乳酸酯;C12-C15烷基乳酸酯;异硬脂醇乳酸酯;月桂醇乳酸酯;亚油醇乳酸酯;油醇乳酸酯;(异)硬脂醇辛酸酯;异鲸蜡醇辛酸酯;辛酸辛酯;辛酸鲸蜡酯;油酸癸酯;异鲸蜡醇异硬脂酸酯;异鲸蜡醇月桂酸酯;异鲸蜡醇硬脂酸酯;辛酸异癸酯;油酸异癸酯;异壬酸异壬酯;棕榈酸异硬脂基酯;乙酰基蓖麻油酸甲酯;肉豆蔻醇硬脂酸酯;异壬酸辛酯;异壬酸2-乙基己酯;棕榈酸辛酯;壬酸辛酯;硬脂酸辛酯;芥酸辛基十二烷基酯;芥酸油酯;棕榈酸乙酯和棕榈酸异丙酯;棕榈酸2-乙基己酯、棕榈酸2-辛基癸酯、肉豆蔻酸烷基酯(诸如肉豆蔻酸异丙酯、肉豆蔻酸丁酯、肉豆蔻酸鲸蜡酯、肉豆蔻酸2-辛基十二烷基酯、肉豆蔻酸肉豆蔻酯、肉豆蔻酸硬脂酸酯)、硬脂酸己酯、硬脂酸丁酯、硬脂酸异丁酯;苹果酸二辛酯、月桂酸己酯、月桂酸2-己基癸酯以及它们的混合物。
在一些实施方案中,该毛发护理组合物还可包含癸二酸二乙酯、癸二酸二异丙酯、己二酸二异丙酯、己二酸二(正丙酯)、己二酸二辛酯、己二酸二异硬脂醇酯、马来酸二辛酯、十一碳烯酸甘油酯、硬脂酰硬脂酸辛基十二烷基酯、单蓖麻油酸季戊四醇酯、四异壬酸季戊四醇酯、四壬酸季戊四醇酯、四异硬脂酸季戊四醇酯、四辛酸季戊四醇酯、二辛酸丙二醇酯、二癸酸丙二醇酯、芥酸十三烷基酯、柠檬酸三异丙酯、柠檬酸三异硬脂醇酯、三乳酸甘油酯、三辛酸甘油酯、柠檬酸三辛基十二烷基酯、柠檬酸三油酯、二辛酸丙二醇酯、二庚酸新戊二醇酯、二异壬酸二乙二醇酯和二硬脂酸聚乙二醇酯及它们的混合物。
在一些实施方案中,该毛发护理组合物还可包含一种或多种脂肪酸酯、一种或多种糖酯和/或一种或多种C6-C30(诸如C12-C22)脂肪酸的二酯。术语“糖”意指含有几个醇官能团、具有或不具有醛或酮官能团并且包含至少4个碳原子的基于含氧烃的化合物。合适的糖可包括单糖、寡糖或多糖,例如蔗糖(或甘蔗糖)、葡萄糖、半乳糖、核糖、岩藻糖、麦芽糖、果糖、甘露糖、阿拉伯糖、木糖和乳糖,以及它们的衍生物,诸如烷基衍生物,诸如甲基衍生物,例如甲基葡萄糖。合适的酯可包括油酸酯、月桂酸酯、棕榈酸酯、肉豆蔻酸酯、山嵛酸酯、椰油酸酯、硬脂酸酯、亚油酸酯、亚麻酸酯、癸酸酯、花生四烯酸酯或它们的混合物,诸如油酸酯/棕榈酸酯、油酸酯/硬脂酸酯或棕榈酸酯/硬脂酸酯混合酯。合适的单酯和二酯还包括蔗糖、葡萄糖或甲基葡萄糖的单或二-油酸酯、单或二-硬脂酸酯、单或二-山嵛酸酯、单或二-油棕榈酸酯、单或二-亚油酸酯、单或二-亚麻酸酯或单或二-油硬脂酸酯,包括由Amerchol公司以名称GLUCATE DO销售的产品,该产品为甲基葡萄糖二油酸酯。还可以提到的糖和脂肪酸的其他示例性的酯或酯类混合物包括:由Crodesta公司以名称F160、F140、F110、F90、F70和SL40销售的产品,分别表示由73%单酯和27%二酯和三酯,由61%单酯和39%二酯、三酯和四酯,由52%单酯和48%二酯、三酯和四酯,由45%单酯和55%二酯、三酯和四酯,由39%单酯和61%二酯、三酯和四酯以及蔗糖单月桂酸酯形成的蔗糖棕榈酸酯/硬脂酸酯;以名称Ryoto Sugar Esters销售的产品,例如参考号B370并且对应于由20%单酯和80%二酯-三酯-聚酯形成的蔗糖山嵛酸酯;由Goldschmidt公司以名称TEGOSOFT PSE销售的蔗糖单-二棕榈酸酯/硬脂酸酯。
在一些实施方案中,该毛发护理组合物还可包含pH调节剂诸如柠檬酸和/或氢氧化钠。毛发护理组合物的任何常用pH调节剂均考虑在本文中使用。
在各种实施方案中,该毛发护理组合物还可包含以下任何成分和/或它们的混合物:月桂酰甲基羟乙基磺酸钠(清洁剂和起泡剂)、液体脂肪物质(包括不同于本文以上讨论的非氨基聚烷基硅氧烷的硅油)和包含至少一个选自氨基、芳基和烷氧基的官能团的有机改性聚硅氧烷。有机聚硅氧烷在Walter Noll的Chemistry and Technology of Silicones(1968),Academic Press中有更详细的定义,其全部内容特此以引用方式并入。它们可以是挥发性的或非挥发性的。合适的环状聚二烷基硅氧烷包括由Union Carbide以名称VOLATILE SILICONE 7207销售或由Rhodia以名称SILBIONE 70045V2销售的八甲基环四硅氧烷,由Union Carbide以名称VOLATILE SILICONE 7158销售和由Rhodia以名称SILBIONE70045V5销售的十甲基环五硅氧烷,以及它们的混合物。二甲基硅氧烷/甲基烷基硅氧烷类型的环共聚物,诸如由Union Carbide公司销售的VOLATILE SILICONE FZ 3109也是合适的。具有有机硅化合物的示例性环状聚二烷基硅氧烷包括八甲基环四硅氧烷和四(三甲基甲硅烷基)季戊四醇(50/50)以及八甲基环四硅氧烷与氧基-1,1'-双(2,2,2',2',3,3'-六-三甲基甲硅烷氧基)新戊烷、直链挥发性聚二烷基硅氧烷(诸如由Toray Silicone公司以名称SH 200销售的那些)的混合物。在Cosmetics and Toiletries,第91卷,1月76期,第27-32页,Todd&Byers,“Volatile Silicone Fluids for Cosmetics”中也描述了属于该类别的硅酮,该文献以引用方式并入本文。
示例性的合适的非挥发性聚二烷基硅氧烷包括具有三甲基甲硅烷基端基的聚二甲基硅氧烷,诸如Rhodia销售的47和70 047系列的SILBIONE油或MIRASIL油,例如70 047V500 000油;由Rhodia销售的MIRASIL系列的油;来自Dow Corning公司的200系列的油,诸如粘度为60000mm2/s的DC200;来自General Electric的VISCASIL油和来自GeneralElectric的SF系列的某些油(SF 96、SF 18),以名称聚二甲基硅氧烷醇(CTFA)已知的具有二甲基硅烷醇端基的聚二甲基硅氧烷,诸如来自Rhodia公司的系列48的油。
示例性的有机改性的硅酮包括聚烷基芳基硅氧烷,以及以下列名称销售的产品:来自Rhodia的70 641系列的SILBIONE油;来自Rhodia的RHODORSIL 70 633和763系列的油;来自Dow Corning的油Dow Corning556化妆品级流体;来自Bayer的PK系列的硅酮,诸如产品PK20;来自Bayer的PN系列和PH系列的硅酮,诸如产品PN1000和PH1000;来自GeneralElectric的SF系列的某些油,诸如SF 1023、SF 1154、SF 1250和SF 1265;由Genesee以名称GP 4Silicone Fluid和GP 7100销售的产品或由Dow Corning公司以名称Q2 8220和DowCorning 929或939销售的产品。
在各种实施方案中,该毛发护理组合物还可包含一种或多种不同于上述阳离子表面活性剂的附加表面活性剂,包括阴离子表面活性剂、两性表面活性剂或两性离子表面活性剂、非离子表面活性剂以及它们的混合物。示例性的阴离子表面活性剂包括烷基硫酸盐、烷基醚硫酸盐、烷基酰胺醚硫酸盐、烷基芳基聚醚硫酸盐、单甘油硫酸盐、烷基磺酸盐、烷基酰胺磺酸盐、烷基芳基磺酸盐、α-烯烃磺酸盐、石蜡磺酸盐、烷基磺基琥珀酸盐、烷基醚磺基琥珀酸盐、烷基酰胺磺基琥珀酸盐、烷基磺基乙酸盐、酰基肌氨酸盐、酰基谷氨酸盐、烷基磺基琥珀酰胺酸盐、酰基羟乙基磺酸盐和N--(C1-C4)烷基N-酰基牛磺酸盐、烷基单酯和多糖苷-多羧酸的盐、酰基乳酸盐、D-半乳糖苷糖醛酸盐、烷基醚羧酸盐、烷基芳基醚羧酸盐、烷基酰胺醚羧酸盐;以及所有这些化合物的相应非成盐形式;所有这些化合物的烷基和酰基(除非另外提到)通常包含6至24个碳原子并且芳基通常表示苯基。盐形式的阴离子表面活性剂可包括碱金属盐诸如钠盐或钾盐、钠盐、铵盐、胺盐和氨基醇盐,或碱土金属盐诸如镁盐。示例性的氨基醇盐包括单乙醇胺、二乙醇胺和三乙醇胺盐、单异丙醇胺、二异丙醇胺或三异丙醇胺盐、2-氨基-2-甲基-1-丙醇盐、2-氨基-2-甲基-1,3-丙二醇盐和三(羟甲基)氨基甲烷盐。
合适的阴离子表面活性剂还包括温和的阴离子表面活性剂,即不具有硫酸根官能团的阴离子表面活性剂,包括聚氧亚烷基化的烷基醚羧酸;聚氧亚烷基化烷芳基醚羧酸;聚氧亚烷基化烷基酰胺醚羧酸,尤其是包含2至50个环氧乙烷基团的那些;烷基-D-半乳糖苷糖醛酸;酰基肌氨酸盐、酰基谷氨酸盐;和烷基多糖苷羧酸酯,诸如从Kao以名称AKYPO RLM45CA销售的那些。
示例性的合适的两性表面活性剂或两性离子表面活性剂可以是任选季铵化的脂族仲胺或叔胺衍生物,其中脂族基团是含有8至22个碳原子的直链或支链,其中胺衍生物含有至少一个阴离子基团,例如羧酸根、磺酸根、硫酸根、磷酸根或膦酸根基团,诸如(C8-C20)烷基甜菜碱、磺基甜菜碱、(C8-C20)烷基酰胺(C3-C8)烷基甜菜碱或(C8-C20)烷基酰胺(C6-C8)烷基磺基甜菜碱。任何合适的脂族仲胺或叔胺衍生物可存在于椰子油或水解亚麻籽油等中。代表性化合物在CTFA词典1993年第5版中被分类在以下名称下:椰油酰两性基二乙酸二钠、月桂酰两性基二乙酸二钠、癸酰两性基二乙酸二钠、辛酰两性基二乙酸二钠、椰油酰两性基二丙酸二钠、月桂酰两性基二丙酸二钠、癸酰两性基二丙酸二钠、辛酰两性基二丙酸二钠、月桂酰两性基二丙酸和椰油酰两性基二丙酸。
举例来说,由Rhodia公司以商品名SODIUM C2M Concentrate销售的椰油酰两性基二乙酸盐和由Chimex公司以名称Chimexane HB销售的二乙基氨基丙基椰油酰天冬酰胺适合用于所公开的组合物中。
合适的非离子表面活性剂在Blackie&Son公开的M.R.Porter的Handbook ofSurfactants(Glasgow and London),1991,第116-178页中有描述,并且包括脂肪醇、脂肪α-二醇、脂肪(C1-C20)烷基酚和脂肪酸,这些可以是乙氧基化、丙氧基化或甘油化的并且含有至少一条包含8至18个碳原子的脂肪链,环氧乙烷或环氧丙烷基团的数目范围为1至200且甘油基团的数目范围为1至30。环氧乙烷和环氧丙烷与脂肪醇的缩合物、具有1至30个环氧乙烷单元的乙氧基化脂肪酰胺、平均包含1至5个甘油基团且尤其是1.5至4个甘油基团的聚甘油化脂肪酰胺、含有1至30个环氧乙烷单元的脱水山梨糖醇的乙氧基化脂肪酸酯、蔗糖的脂肪酸酯、聚乙二醇的脂肪酸酯、(C6-C24)烷基多糖苷、氧乙烯化植物油、N-(C6-C24)烷基葡糖胺衍生物、氧化胺诸如(C10-C14)烷基胺氧化物或N-(C10-C14)酰基氨基丙基吗啉氧化物也适合用于本文公开的组合物中。
其他合适的非离子表面活性剂包括烷基多葡糖苷(APG)、麦芽糖酯、聚甘油化脂肪醇、葡糖胺衍生物(例如2-乙基己氧基羰基-N-甲基葡糖胺)及它们的混合物。烷基多葡糖苷是含有包含6至30个碳原子的烷基并且含有亲水性基团(葡糖苷)的那些烷基多葡糖苷。示例性烷基多葡糖苷包括癸基葡糖苷(烷基-C9/C11-多葡糖苷(1.4)),包括由Kao Chemicals公司以名称Mydol销售的产品,由Cognis公司以名称Plantaren 2000/>销售的产品和由SEPPIC公司以名称Oramix NS/>销售的产品;以及辛基/癸基葡糖苷,包括由SEPPIC公司以名称Oramix CG/>销售的产品;由Cognis公司以Plantaren 1200/>和Plantacare销售的月桂基葡糖苷,以及椰油基葡糖苷,例如由Cognis公司以名称Plantacare818//>销售的产品。
合适的麦芽糖衍生物包括文件EP-A-566 438中描述的那些,诸如文件FR-2 739556中描述的0-辛酰基-6'-D-麦芽糖或O-十二酰基-6'-D-麦芽糖。这些文件中的每一个文件都以引用方式整体并入。
在一些实施方案中,该毛发护理组合物可以配制在美容上可接受的介质中。术语“美容上可接受的介质”意指与人角蛋白纤维诸如毛发相容的介质。美容上可接受的介质可以由水或由水和一种或多种美容上可接受的溶剂的混合物形成,该溶剂选自低级醇,诸如乙醇和异丙醇;多元醇和多元醇醚,包括2-丁氧基乙醇、丙二醇、丙二醇单甲醚、二乙二醇单乙醚和单甲醚以及它们的混合物。
在一些实施方案中,该毛发护理组合物还可包含以下任何添加剂或它们的混合物:不同于脂肪醇的固体脂肪物质诸如蜡、阴离子聚合物、非离子聚合物或两性聚合物或它们的混合物,去头屑剂、抗皮脂溢剂、用于防止脱发和/或用于促进毛发再生的试剂、维生素和维生素原(包括泛醇)、防晒剂、无机颜料或有机颜料、螯合剂、增塑剂、增溶剂、酸化剂、无机增稠剂或有机增稠剂(特别是不同于氧乙烯化聚合物的聚合物增稠剂)、遮光剂或珠光剂、抗氧化剂、羟酸、香味剂和/或防腐剂。
指甲护理
在一些实施方案中,该美容组合物可包含通常用于指甲护理产品中的成分。指甲护理产品包括但不限于指甲处理剂(包括指甲强化剂、面涂层和底涂层)、指甲抛光剂、指甲抛光剂去除剂、手部皮肤护理剂、脚部皮肤护理剂、干燥剂和修正笔(包括指甲抛光剂去除剂)。
在一些实施方案中,该指甲护理组合物可以是指甲处理组合物。指甲处理组合物可以包括用于处理向内生长的指甲或指甲畸形的组合物、用于指甲感染(包括真菌感染)的局部处理的组合物、指甲强化剂、面涂层、底涂层、抛光剂去除剂或它们的任何组合。在一些实施方案中,指甲处理组合物可以配制为用于处理手和/或脚的局部指甲漆或指甲抛光剂、乳霜、溶液、悬浮液、洗剂、精华液、凝胶、香脂、凝胶、油、乳霜包油和/或擦剂。
在一些实施方案中,该指甲处理组合物可以是指甲强化剂。指甲强化剂可处理手指甲和脚趾甲以硬化、强化指甲和促进指甲的生长,以防止或最小化断裂、开裂、分裂和剥离,并且可包括用于防止和愈合侧壁蹄裂(quarter crack),同时增加马蹄生长的任何已知组合物,该组合物具有与人手指甲和脚趾甲相似的蛋白稠度,包括:羊毛脂、牛油、蜂蜡、松香、乙酸铜和松节油。在一些实施方案中,指甲处理组合物还可包含二氧化钛,例如来自E.I.DuPont的TI-PURE R900。
在一些实施方案中,该指甲处理组合物可以是底涂层。在一些实施方案中,底涂层可以是包含至少一种提供粘附力的聚合物的液体组合物,例如聚合物由甲基丙烯酸甲酯(MMA)和甲基丙烯酸(MAA)共聚以形成由聚甲基丙烯酸甲酯(PMMA)和聚甲基丙烯酸(PMAA)组成的聚合物,其中MAA单体分数可以从0至100%变化。在一些实施方案中,用作底涂层的合适聚合物包括甲基丙烯酸羟乙酯(HEMA)、甲基丙烯酸羟丙酯(HPMA)、甲基丙烯酸乙酯(EMA)、甲基丙烯酸四氢糠基酯(THFMA)、均苯四甲酸二酐二(甲基)丙烯酸酯、均苯四甲酸二酐甘油二甲基丙烯酸酯、均苯四甲酸二甲基丙烯酸酯、甲基丙烯酰氧基乙基马来酸酯、2-羟乙基甲基丙烯酸酯/琥珀酸酯、1,3-甘油二甲基丙烯酸酯/琥珀酸酯加合物、邻苯二甲酸单乙基甲基丙烯酸酯以及它们的混合物。在一些方面,底涂层还可包含非反应性、可溶于溶剂的成膜聚合物,诸如纤维素酯,例如乙酸烷基化物纤维素、乙酸丁酸纤维素或乙酸丙酸纤维素。上述示例性成分不是限制性的。
在一些实施方案中,该指甲处理组合物可以是面涂层,例如快干面涂层。面涂层可以包括是乙酸丁酸纤维素的基础树脂,是甲基丙烯酸酯聚合物的成膜剂,是单官能甲基丙烯酸酯和交联剂(即,双官能甲基丙烯酸酯和三官能甲基丙烯酸酯)的可热固化或可光固化单体,一起在脂族酯和醇的溶液中的热引发剂或光引发剂以及光反应性涂层。合适的溶剂包括乙酸酯和醇,特别是乙酸乙酯、乙酸丁酯和异丙醇。光反应性涂层可以包括光反应性单体,包括甲基丙烯酸酯单体,诸如:甲基丙烯酸环己酯、甲基丙烯酸正癸酯、甲基丙烯酸2-乙基己酯、甲基丙烯酸乙酯、甲基丙烯酸羟丙酯、甲基丙烯酸异冰片酯、甲基丙烯酸2-甲氧基乙酯;双官能和三官能甲基丙烯酸酯单体、交联剂诸如二氨基甲酸酯二甲基丙烯酸酯、乙二醇二甲基丙烯酸酯、1,10-癸二醇二甲基丙烯酸酯、1,6-己二醇二甲基丙烯酸酯和三羟甲基丙烷三甲基丙烯酸酯。适合使用的市售光引发剂包括但不限于:安息香甲基醚、2-羟基-2-甲基-1-苯基-1-丙酮(“Darocur 1173”)、二乙氧基苯乙酮和苄基二缩酮。光引发剂是苯基丙酮的低聚混合物,诸如2,4,6-三甲基二苯甲酮和4-甲基二苯甲酮的混合物以及低聚-[2-羟基-2-甲基-1[4-(1-甲基乙烯基)苯基]丙酮]和2-羟基-2-甲基-苯基丙酮的混合物,该混合物由Sartomer以名称“Esacure KIP 100F”和“Esacure TZT光引发剂”销售。
在一些实施方案中,该指甲护理组合物可以是指甲抛光剂或指甲油组合物。在一些实施方案中,指甲抛光剂或指甲油组合物还可包含硝化纤维素成膜剂、乳胶成膜剂、聚碳二亚胺成膜剂、低挥发性有机化合物(VOC)和聚碳二亚胺成膜剂。聚碳二亚胺可包括具有多个附于聚合物主链上的碳二亚胺基团的聚合物。例如,美国专利第5,352,400号(其公开内容以引用方式并入本文)公开了衍生自α-甲基苯乙烯基-异氰酸酯的聚合物和共聚物。合适的聚碳化二亚胺化合物包括但不限于由供应商Nisshinbo(包括以名称CARBODILITE系列V-02、V02-L2、SV-02、E-02、V-10、SW-12G、E-03A已知的那些)、Picassian和3M市售的那些。
在一些实施方案中,指甲抛光剂或指甲油组合物还可包含一种或多种乳胶聚合物,包括羧基官能丙烯酸酯乳胶聚合物、羧基官能聚氨酯乳胶聚合物、羧基官能硅酮乳胶聚合物、羧基官能非丙烯酸酯乳胶聚合物及它们的混合物。在各种实施方案中,合适的乳胶聚合物可以是成膜乳胶聚合物或非成膜乳胶聚合物。在一些实施方案中,乳胶聚合物可以是羧基官能丙烯酸酯乳胶聚合物,诸如由选自以下的烯键式不饱和单体均聚或共聚产生的那些:乙烯基单体、(甲基)丙烯酸单体、(甲基)丙烯酰胺单体、不饱和单羧酸和二羧酸、(甲基)丙烯酸单体的酯和(甲基)丙烯酸单体的酰胺。如本文所用,术语“(甲基)丙烯酰基”及其变型意指丙烯酰基或甲基丙烯酰基。(甲基)丙烯酸单体可以选自例如丙烯酸、甲基丙烯酸、柠康酸、衣康酸、马来酸、富马酸、巴豆酸和马来酸酐。作为非限制性示例,(甲基)丙烯酸单体的酯可以是(甲基)丙烯酸C1-C8烷基酯,诸如(甲基)丙烯酸甲酯、(甲基)丙烯酸乙酯、(甲基)丙烯酸丙酯、(甲基)丙烯酸异丙酯、(甲基)丙烯酸丁酯、(甲基)丙烯酸叔丁酯、(甲基)丙烯酸戊酯、(甲基)丙烯酸异戊酯、(甲基)丙烯酸新戊酯、(甲基)丙烯酸己酯、(甲基)丙烯酸异己酯、(甲基)丙烯酸2-乙基己酯、(甲基)丙烯酸环己酯、(甲基)丙烯酸异己酯、(甲基)丙烯酸庚酯、(甲基)丙烯酸异庚酯、(甲基)丙烯酸辛酯、(甲基)丙烯酸异辛酯、(甲基)丙烯酸烯丙酯以及它们的组合。(甲基)丙烯酸单体的酰胺可以例如由(甲基)丙烯酰胺,尤其是N-烷基(甲基)丙烯酰胺,尤其是(甲基)丙烯酸N--(C1-C12)烷基酯,诸如N-乙基(甲基)丙烯酰胺、N-叔丁基(甲基)丙烯酰胺、N-叔辛基(甲基)丙烯酰胺、N-羟甲基(甲基)丙烯酰胺和N-双丙酮(甲基)丙烯酰胺以及它们的组合制成。
乙烯基单体可以包括但不限于乙烯基氰化合物诸如丙烯腈和甲基丙烯腈;乙烯酯类,诸如甲酸乙烯酯、乙酸乙烯酯、丙酸乙烯酯、新癸酸乙烯酯、新戊酸乙烯酯、苯甲酸乙烯酯和苯甲酸乙烯-叔丁酯、三聚氰酸三烯丙酯;乙烯基卤化物,诸如氯乙烯和偏二氯乙烯;芳族单乙烯基或二乙烯基化合物,诸如苯乙烯、.α.-甲基苯乙烯、氯苯乙烯、烷基苯乙烯、二乙烯基苯和邻苯二甲酸二烯丙酯,以及对苯乙烯磺酸、乙烯基磺酸、2-(甲基)丙烯酰氧基乙基磺酸、2-(甲基)丙烯酰胺-2-甲基丙基磺酸以及它们的混合物。
本文的单体列表不是限制性的,并且应当理解,可以使用本领域技术人员已知的任何单体,包括丙烯酸单体和/或乙烯基单体(包括用硅酮链改性的单体)。
在一些非限制性示例性实施方案中,羧基官能丙烯酸酯乳胶聚合物可以选自以下的水性分散体:甲基丙烯酸/丙烯酸乙酯共聚物(INCI:丙烯酸酯共聚物,诸如BASF的LUVIFLEX SOFT)、PEG/PPG-23/6二甲聚硅氧烷柠康酸酯/C10-30烷基PEG-25甲基丙烯酸酯/丙烯酸/甲基丙烯酸/丙烯酸乙酯/三羟甲基丙烷PEG-15三丙烯酸酯共聚物(INCI:聚丙烯酸酯-2交联聚合物,诸如Lubrizol的Fixate Superhold.TM.)、苯乙烯/丙烯酸共聚物(诸如Dow Chemical的Acudyne Shine)、丙烯酸乙基己酯/甲基丙烯酸甲酯/丙烯酸丁酯/丙烯酸/甲基丙烯酸共聚物(INCI:丙烯酸酯/丙烯酸乙基己酯共聚物,例如Daitosol 5000SJ,DaitoKasei Kogyo)、丙烯酸/丙烯酸酯共聚物(INCI名称:丙烯酸酯共聚物,诸如Daitosol5000AD,Daito Kasei Kogyo)、丙烯酸酯共聚物(诸如以商品名Dermacryl AQF(AkzoNobel)、以商品名LUVIMER MAE(BASF)或以商品名BALANCE CR(AKZO NOBEL)已知的那些)、丙烯酸酯/羟基酯丙烯酸酯共聚物(以商品名ACUDYNE 180POLYMER(Dow Chemical)已知)、苯乙烯/丙烯酸酯共聚物(来自Dow Chemical,以商品名Acudyne Bold已知)、苯乙烯/丙烯酸酯/甲基丙烯酸铵共聚物(来自Interpolymer,以商品名SYNTRAN PC5620 CG已知)以及它们的混合物。
在一些实施方案中,该指甲护理组合物可包含指甲抛光剂去除剂。指甲抛光剂去除剂可包括多元醇化合物,包括甘油、二醇、聚甘油、多元醇的酯及它们的混合物。二醇可以含有2至12个碳原子,例如甘油、丙二醇、丁二醇、丙二醇、己二醇、聚甘油、二丙二醇和二乙二醇。合适的多元醇的酯包括饱和或不饱和的直链或支链C1-C26多元醇的液体酯。合适的多元醇的酯的示例包括但不限于二羟基醇、三羟基醇、四羟基醇或五羟基醇的酯。多元醇的酯可以是甘油酯,诸如三乙醇酸甘油酯、三柠檬酸甘油酯、三乳酸甘油酯、三乳酸甘油酯、三丁酸甘油酯、三庚酸甘油酯、三辛酸甘油酯等。
指甲抛光剂去除剂还可包含低碳醇,含有1至8个碳原子。低碳醇可含有2至6个碳原子,诸如2至5个碳原子。低碳醇的示例包括但不限于乙醇、丙醇、丁醇、戊醇、异丙醇、异丁醇和异戊醇。指甲抛光剂去除剂还可包含高沸点酯化合物,包括但不限于碳酸酯、己二酸酯、癸二酸酯和琥珀酸酯。示例性的高沸点酯化合物包括但不限于碳酸亚烷基酯,诸如碳酸丙烯酯、琥珀酸二甲酯、琥珀酸二乙酯、戊二酸二甲酯、戊二酸二乙酯、癸二酸二甲酯、癸二酸二乙酯、癸二酸二异丙酯、双(2-乙基己基)癸二酸酯、己二酸二甲酯、己二酸二异丙酯、己二酸二正丙酯、己二酸二辛酯、双(2-乙基己基)己二酸酯、己二酸二异硬脂基酯、马来酸乙酯、双(2-乙基己基)马来酸酯、柠檬酸三异丙酯、柠檬酸三异鲸蜡酯、柠檬酸三异硬脂基酯、柠檬酸三辛基十二烷基酯和柠檬酸三油酯。
指甲抛光剂去除剂还可包含增稠试剂,包括但不限于:非离子聚合物、阴离子聚合物、阳离子聚合物、两亲聚合物和两性聚合物,以及其他已知的流变改性剂,诸如基于纤维素的增稠剂,诸如羟乙基纤维素、羟丙基纤维素、甲基纤维素和乙基羟乙基纤维素。某些值得注意的纤维素衍生物包括羟基改性的纤维素聚合物,诸如羟乙基纤维素,例如分子量超过500,000道尔顿的那些,诸如NATROSOL 250HHR和羟丙基纤维素,例如KLUCEL MF--两者均可得自Ashland,Covington,Ky。增稠试剂可以是多糖诸如果聚糖、葡聚糖、半乳聚糖和甘露聚糖,或杂多糖诸如半纤维素、普鲁兰多糖(pullulan)或支链多糖诸如阿拉伯树胶和支链淀粉,或混合多糖诸如淀粉。增稠试剂可以是丙烯酸增稠试剂(丙烯酸增稠剂)或丙烯酰胺增稠试剂(丙烯酰胺增稠剂)。增稠试剂可以包括至少一种执行弱酸功能的单体,诸如丙烯酸、甲基丙烯酸、衣康酸、巴豆酸、马来酸和/或富马酸。增稠试剂可包括执行强酸功能的单体,诸如具有磺酸型或膦酸型功能的单体,诸如2-丙烯酰胺-2-甲基丙磺酸(AMPS)。增稠试剂可包括交联剂诸如亚甲基双丙烯酰胺(MBA)、乙二醇二丙烯酸酯、聚乙二醇二甲基丙烯酸酯、二丙烯酰胺、氰基甲基丙烯酸酯、乙烯氧基乙基丙烯酸酯或甲基丙烯酸酯、甲醛、乙二醛和缩水甘油醚类型的组合物诸如乙二醇二缩水甘油醚或环氧化物。合适的丙烯酸增稠剂公开于美国专利申请公开第2004/0028637号和第2008/0196174号中,两者均以引用方式并入本文。在一些实施方案中,增稠试剂可包括有机粘土(疏水处理的粘土)或亲水性粘土。
在一些实施方案中,增稠试剂可包括磨料化合物(磨料体系)。“磨料化合物”是能够提供研磨或机械剥离的化合物。磨料颗粒可包括珍珠岩、浮石、沸石、水合二氧化硅、碳酸钙、二水合磷酸二钙、焦磷酸钙、氧化铝、碳酸氢钠、聚乳酸以及合成聚合物材料诸如聚乙烯、聚丙烯、聚对苯二甲酸乙二酯、聚甲基丙烯酸甲酯或尼龙。在某些实施方案中,中等硬度的磨料包括珍珠岩,诸如可以名称IMERCARE 270P-Scrub从Imerys获得的美容级珍珠岩。在某些实施方案中,软磨料是糖、磨碎的果核或果壳粉末,例如杏仁、椰子壳或球形蜡(例如,巴西棕榈荷荷巴油(carnauba jojoba));摩洛哥坚果壳粉末等。
在一些实施方案中,该指甲护理组合物还可包含常用于美容组合物中且为技术人员已知的添加剂,包括溶剂、防腐剂、香味剂、油、蜡、表面活性剂、抗氧化剂、抗自由基的试剂、润湿剂、分散剂、消泡剂、中和剂、稳定剂,选自精油、UV遮蔽剂、防晒剂、增湿剂、维生素、蛋白、神经酰胺、植物提取物、纤维等的活性成分、以及它们的混合物。
d.治疗组合物
在一些实施方案中,本文所述的组合物可以是用于治疗一种或多种病状的治疗组合物。例如,在一些实施方案中,施加本文所述的组合物可促进伤口愈合、减少或防止疤痕组织的形成、促进组织再生、使局部炎症最小化、使组织排斥最小化和/或增强移植物整合。在一些实施方案中,该组合物可以配制为可注射材料,例如水凝胶。胶原水凝胶呈现出大的均匀表面积,并且可用作胶原和任选地一种或多种附加治疗剂的递送系统。可注射胶原材料还可以形成能够替代组织功能和支持组织再生的支架或网络。在某些实施方案中,该组合物可以局部施加。在某些实施方案中,该组合物可以经皮、皮内或皮下注射。
在一些实施方案中,本文所述的治疗组合物可包含除本文别处所述的胶原片段以外的一种或多种附加治疗剂和/或预防剂。该一种或多种附加治疗剂和/或预防剂可以是小分子活性剂或生物分子,诸如酶或蛋白、多肽或核酸。
附加治疗剂和/或预防剂的非限制性示例包括抗癌剂、抗微生物剂(包括抗病毒剂、抗细菌剂、抗真菌剂和抗寄生虫剂)、抗氧化剂、镇痛剂、局部麻醉剂、抗炎剂、细胞因子、免疫抑制剂、抗过敏剂、必需营养物、生长因子(诸如成纤维细胞生长因子、肝细胞生长因子、血小板源性生长因子、血管内皮细胞生长因子和胰岛素样生长因子)及它们的组合。本领域技术人员可以容易地确定附加治疗和/或预防剂的具体剂量。参见Ansel,Howard C.等人,Pharmaceutical Dosage Forms and Drug Delivery Systems(第6版)Williams和Wilkins,Malvern,PA(1995)。
在其他实施方案中,本文所述的重组胶原片段组合物可与细胞递送组合使用,例如,干细胞、多能细胞、体细胞及它们的组合的递送。
尽管本公开考虑到治疗剂和/或预防剂将是本文所述的组合物不可或缺的部分,但在一些实施方案中,治疗剂和/或预防剂可在施用本文所述的治疗组合物之前、同时或之后施用。换句话讲,在一些实施方案中,该一种或多种附加治疗剂和/或预防剂可以不整体掺入本发明组合物中,而是与本发明组合物分开提供。
能够包含在本发明组合物中的合适的局部麻醉剂的非限制性示例包括但不限于,氨布卡因(ambucaine)、阿莫拉酮(amolanone)、阿米洛卡因(amylocaine)、丁氧普鲁卡因(benoxinate)、苯佐卡因(benzocaine)、丁氧卡因(betoxycaine)、苯柳胺酯(biphenamine)、布比卡因(bupivacaine)、布他卡因(butacaine)、氨苯丁酯(butamben)、布坦卡因(butanilicaine)、丁胺卡因(butethamine)、丁氧卡因(butoxycaine)、卡替卡因(carticaine)、氯普鲁卡因(chloroprocaine)、古柯乙烯(cocaethylene)、可卡因(cocaine)、环美卡因(cyclomethycaine)、地布卡因(dibucaine)、二甲异喹(dimethysoquin)、二甲卡因(dimethocaine)、地哌冬(diperodon)、达克罗宁(dycyclonine)、芽子定(ecgonidine)、芽子碱(ecgonine)、乙基氯、依替卡因(etidocaine)、β-优卡因(eucaine)、尤普罗(euprocin)、非那可明(fenalcomine)、福尔卡因(formcaine)、海克卡因(hexylcaine)、羟丁卡因(hydroxy tetracaine)、对氨基苯甲酸异丁酯、甲磺酸亮氨卡因、左沙屈尔(levoxadrol)、利多卡因(lidocaine)、卡波卡因(mepivacaine)、美普卡因(meprylcaine)、美布卡因(metabutoxycaine)、甲基氯、麦替卡因(myrtecaine)、纳帕因(naepaine)、奥他卡因(octacaine)、奥索卡因(orthocaine)、奥昔卡因(oxethazaine)、对乙氧卡因(parethoxycaine)、非那卡因(phenacaine)、苯酚、哌罗卡因(piperocaine)、匹多卡因(piridocaine)、聚多卡醇(polidocanol)、普莫卡因(pramoxine)、丙胺卡因(prilocaine)、普鲁卡因(procaine)、丙泮卡因(propanocaine)、丙美卡因(proparacaine)、丙哌卡因(propipocaine)、丙氧卡因propoxycaine)、假可卡因(psuedococaine)、吡咯卡因(pyrrocaine)、罗哌卡因(ropivacaine)、水杨醇、丁卡因(tetracaine)、托利卡因(tolycaine)、三甲卡因(trimecaine)、佐拉敏(zolamine)及它们的组合。
合适的抗病毒剂的非限制性示例包括更昔洛韦(ganciclovir)和阿昔洛韦(acyclovir)。合适的抗生素剂的非限制性示例包括氨基糖苷类诸如链霉素、阿米卡星(amikacin)、庆大霉素和妥布霉素;安沙霉素类诸如格尔德霉素(geldanamycin)和除莠霉素(herbimycin);碳头孢烯类;碳青霉烯类;头孢菌素类;糖肽类诸如万古霉素、替考拉宁(teicoplanin)和泰拉万欣(telavancin);林可酰胺类;脂肽类诸如达托霉素(daptomycin);大环内酯类诸如阿齐霉素(azithromycin)、克拉霉素(clarithromycin)、地红霉素(dirithromycin)和红霉素(erythromycin);单胺菌素类;硝基呋喃类;青霉素类;多肽类诸如杆菌肽(bacitracin)、粘菌素(colistin)和多粘菌素(polymyxin)B;喹诺酮类;磺酰胺类;和四环素类。另外的示例性抗微生物剂包括碘、银化合物、莫西沙星(moxifloxacin)、环丙沙星(ciprofloxacin)、左氧氟沙星(levofloxacin)、头孢唑啉(cefazolin)、替加环素(tigecycline)、庆大霉素、头孢他啶(ceftazidime)、氧氟沙星(ofloxacin)、加替沙星(gatifloxacin)、两性霉素(amphotericin)、伏立康唑(voriconazole)、那他霉素(natamycin)。
合适的抗炎剂的非限制性示例包括甾体活性剂,包括糖皮质激素、孕激素、盐皮质激素和皮质类固醇。示例性的非甾体抗炎药包括酮咯酸(ketorolac)、布洛芬(ibuprofen)、奈帕芬胺(nepafenac)、双氯酚酸(diclofenac)、阿司匹林(aspirin)和萘普生(naproxen)。其他示例性抗炎剂包括曲安奈德(triamcinolone acetonide)、醋酸氟轻松(fluocinoloneacetonide)、泼尼松龙(prednisolone)、地塞米松(dexamethasone)、氯替泼诺(loteprendol)、氟甲松龙(fluorometholone)和甘草酸二钾(dipotassiumglycyrrhizate)。
在一些实施方案中,该组合物还可包含一种或多种附加药物活性剂。示例性药剂可包括非甾体抗炎剂(NSAID),例如氟比洛芬(flurbiprofen)、布洛芬、萘普生、吲哚美辛(indomethacin)和相关化合物。在一些实施方案中,该组合物还可包含一种或多种抗有丝分裂药物,包括秋水仙碱(colchicine)、紫杉醇(taxol)和相关化合物。在一些实施方案中,该组合物还可包含一种或多种局部消毒剂,例如过氧化苯甲酰。在一些实施方案中,该组合物还可包含由微藻类产生的一种或多种多糖,例如,微藻酸。
在一些实施方案中,该组合物还可包含一种或多种免疫调节药物。示例性的免疫调节药物包括咪喹莫特(imiquimod)、环孢菌素(cyclosporine)、他克莫司(tacrolimus)和雷帕霉素(rapamycin)。
在一些实施方案中,该组合物还可包含一种或多种细胞因子。示例性的合适的细胞因子包括但不限于IL-10、TGF-β、IL-25和IL-35。在某些实施方案中,细胞因子可诱导Treg活化(例如IL-25)并抑制Thl7活化(例如IL-10)以使排斥最小化。
在一些实施方案中,本文所述的组合物还包含至少一种真核细胞类型。一些示例性的真核细胞类型包括干细胞、间充质干细胞、角化细胞、成纤维细胞、黑素细胞、脂肪细胞、免疫细胞诸如T淋巴细胞、B淋巴细胞、天然杀伤细胞和树突细胞,或它们的组合。在一些实施方案中,干细胞可以是脂肪来源的间充质干细胞。可有益于伤口愈合的间充质干细胞的功能特征包括它们能够迁移至损伤或炎症部位、参与受损组织再生、刺激驻留祖细胞的增殖和分化、通过生长因子分泌和基质重塑促进受损细胞的恢复以及发挥独特的免疫调节和抗炎作用(参见例如,Phinney OG等人,Stem Cells,25:2896-2902(2007);ChamberlainG等人,Stem Cells,25:2739-2749(2007);Dazzi F等人,Curr Opin Oncol.19:650-655(2007))。这些参考文献中的每一个参考文献都以引用方式整体并入。
在一些实施方案中,真核细胞可负责增加结缔组织的结构完整性和/或促进愈合。在一些实施方案中,真核细胞(诸如成纤维细胞)可负责增强或促进细胞或组织的生长或连接。
在一些实施方案中,重组胶原组合物可与1)植入的毛发移植物和2)植入毛发移植物的组织接触。用于毛发移植的受体部位包括头皮、面部区、腋窝或胸部区或耻区。面部区的具体区域包括眉毛、眼睑、胡子、鬓角、下巴和脸颊。受体部位可以是受试者需要毛发出现的任何皮肤区域。在一些实施方案中,与不使用本文所述的组合物植入的移植物相比,本文所述的组合物与植入的毛发和受体部位的周围组织之间的接触促进从周围组织到移植物中的营养灌注,并且增加移植物的存活率。在某些实施方案中,本文所述的组合物与植入的毛发之间的接触以及本文所述的组合物与受体部位的周围组织之间的接触促进植入的移植物周围的血管形成,使得移植物的存活率与不使用本文所述的组合物植入的移植物相比增加。
e.膳食组合物
在一些实施方案中,本文所述的组合物可以是可用于向有需要的受试者提供胶原的膳食组合物。例如,在一些实施方案中,消耗本文所述的膳食组合物可提供健康和/或皮肤益处,诸如增加胶原摄取、缓解关节疼痛和改善皮肤健康。在某些实施方案中,该组合物可以是粉末、胶囊、液体形式或任何其他合适的形式。
在一些实施方案中,膳食组合物可包含一种或多种营养成分,诸如:抗坏血酸、生物素、烟酸铬、柠檬酸铜、D-泛酸钙、氰钴胺素、亚麻籽、亚麻、叶酸、低聚果糖(纤维)、氧化镁、柠檬酸锰、麦芽糖糊精、中链甘油三酯、调味剂、烟酰胺、柠檬酸钾、碘化钾、核黄素、甘蔗(saccharum officinarum)、钼酸钠二水合物、硒酸钠(硒)、大豆蛋白分离物、甜叶菊叶提取物/甜叶菊、硫胺素HCl、磷酸三钙、维生素A棕榈酸酯、维生素D3、黄原胶、柠檬酸锌、纤维素胶、瓜尔胶、盐酸吡哆醇、盐、生育酚、抗氧化剂(例如白藜芦醇、CoQ10、巴西莓、番茄红素和石榴)、天然或人工甜味剂(例如葡糖、蔗糖、果糖、糖、环己氨基磺酸盐、阿斯巴甜(aspartamine)、三氯蔗糖、阿司帕坦(aspartame)、安赛蜜K或山梨糖醇)、调味剂(诸如调味提取物、挥发性油、巧克力调味剂(例如非咖啡因可可或巧克力、巧克力替代物诸如角豆)、花生酱调味剂、饼干屑、香草)或任何市售调味剂,及它们的任何组合。
f.产生重组胶原片段的方法
在一些实施方案中,本文所述的重组胶原片段可以在遗传工程化的酵母菌株中产生。合适的酵母菌包括毕赤酵母属(Pichia)、假丝酵母属(Candida)、法夫驹形氏酵母属(Komatagaella)、汉逊酵母属(Hansenula)、隐球酵母属(Cryptococcus)、酵母菌属(Saccharomyces)及它们的组合。在一些实施方案中,酵母可以来自毕赤酵母属。酵母可以进行修饰或杂交。杂交酵母可通过培育相同种的不同菌株、相同属的不同种或不同属的菌株来制备。适于产生本文公开的胶原片段的酵母菌株的示例包括巴斯德毕赤酵母(Pichiapastoris)、膜醭毕赤酵母(Pichia membranifaciens)、沙漠毕赤酵母(Pichiadeserticola)、Pichia cephalocereana、埃塞俄比亚毕赤酵母(Pichia eremophila)、产香酵母(Pichia myanmarensis)、异常毕赤酵母(Pichia anomala)、中濑毕赤酵母(Pichianakasei)、Pichia siamensis、Pichia heedii、巴氏毕赤酵母(Pichia barkeri)、挪威毕赤酵母(Pichia norvegensis)、耐高温毕赤酵母(Pichia thermomethanolica)、树干毕赤酵母(Pichia stipites)、亚膜汉逊毕赤酵母(Pichia subpelliculosa)、甜菜毕赤酵母(Pichia exigua)、西方毕赤酵母(Pichia occidentalis)、仙人掌毕赤酵母(Pichiacactophila)等。在一个具体实施方案中,酵母为巴斯德毕赤酵母(Pichia pastoris)。
在一些实施方案中,该方法包括:(i)在发酵液中发酵遗传工程化的酵母;(ii)从发酵液的上清液中回收由遗传工程化的酵母分泌的重组胶原片段;以及(iii)任选地,纯化重组胶原片段。在一些实施方案中,该方法还包括冻干。
在一些实施方案中,该方法包括:(i)在发酵液中发酵遗传工程化的酵母;(ii)回收基因工程化的酵母未分泌到发酵液的上清液中的细胞内重组胶原片段;以及(iii)任选地,纯化重组胶原片段。在一些实施方案中,该回收包括从全发酵液中回收细胞内重组胶原片段。在一些实施方案中,该回收包括从细胞糊浆回收细胞内重组胶原片段。在一些实施方案中,该方法还包括冻干。
g.使用方法
在一些实施方案中,本文所述的组合物可以是护肤组合物,该护肤组合物可用于通过将护肤组合物局部施用至皮肤区域来治疗该皮肤区域。
本文所述的护肤组合物可施加到任何体表,包括但不限于面部表面、头皮、颈部、耳部、肩部、胸部(包括乳房和/或袒胸部位)、手臂、手、腿部、胃部、臀部、腹股沟、背部、脚以及它们的组合。在一些实施方案中,面部表面可为前额、眼、口周表面、下颚表面、眶周表面、鼻表面、面颊皮肤表面或它们的组合。
在一些实施方案中,将本文所述的组合物施用于皮肤可改善或维持皮肤质量并减少或消除老化迹象。老化迹象包括但不限于所有外部视觉和触觉可感知的表现以及由于皮肤老化导致的任何其他宏观效应或微观效应。此类迹象可由内在因素或外在因素(诸如实足年龄和/或环境损害)诱导或引起。这些迹象可由以下过程引起,这些过程包括但不限于发展组织不连续性,诸如皱纹和粗深皱纹、细纹、皮肤纹、裂缝、隆起、大孔(例如,与附件结构诸如汗腺管、皮脂腺或毛囊相关)或不均匀或粗糙,皮肤弹性损失(功能皮肤弹性蛋白的损失和/或失活)、松垂(包括眼区域和下颌的浮肿)、皮肤紧致度损失、紧缩感损失、皮肤变形弹回的损失、变色(包括眼圈)、出现斑点、灰黄、色素沉着过度的皮肤区域诸如老年斑和雀斑、角化病、异常分化、角化过度、弹性组织变性、胶原分解及角质层、真皮、表皮、皮肤血管系统(例如,毛细管扩张或蜘蛛状血管)和下层组织(例如,脂肪和/或肌肉)中的其他组织学变化,尤其是接近皮肤的那些组织学变化。
在一些实施方案中,如本文所述的组合物可适合用作皮肤填充剂。皮肤填充剂组合物可替代损失的内源基质聚合物,或增强/促进现有基质聚合物的功能,以便治疗由于老化或损伤引起的皮肤病状。皮肤填充剂组合物可填充皱纹、纹、折痕、疤痕,并增强皮肤组织,诸如使薄唇丰满,或填充凹陷的眼睛或浅颊。早期的皮肤填充剂产品通常由胶原制成。现代皮肤填充剂组合物中使用的一种常见基质聚合物是透明质烷。因为透明质烷对人体是天然的,所以它通常是良好耐受的,并且对多种皮肤病状的治疗风险相当低。
在一些实施方案中,如本文所述的组合物可以适合与微针板或贴片一起使用。微针可向面部和身体的任何区域提供本文所述的组合物以实现美容益处或伤口愈合益处。
在一些实施方案中,本文所述的组合物可以是可用于减少或预防疤痕组织形成、促进愈合、促进组织再生、使局部炎症最小化、使组织排斥最小化和/或增强皮肤和/或毛发移植物整合的治疗组合物。
在一些实施方案中,本公开提供了一种治疗皮肤病状的方法,该方法包括将有效量的包含重组胶原片段的组合物施用于有需要的受试者。在一些实施方案中,该皮肤病状可以是细纹、皱纹、干性皮肤、毛孔粗大、皮肤变色、弹性降低、多余毛发、皮肤变薄、紫癜、光化性角化病、瘙痒、湿疹、痤疮、酒渣鼻、红斑、毛细管扩张、光化性毛细管扩张、皮肤癌或肥大性酒渣鼻。
在一些实施方案中,该组合物可局部施用于皮肤区域。在一些实施方案中,该皮肤区域可以选自由以下组成的组:面部表面、头皮、颈部、耳朵、肩部、胸部(包括乳房和/或领口)、手臂、手、腿、胃、臀部、腹股沟、背部、脚以及它们的组合。
在一些实施方案中,该组合物可局部施用于面部表面。在一些实施方案中,该面部表面可以选自由以下组成的组:前额、眼、口周表面、下巴表面、眶周面、鼻表面、脸颊皮肤表面以及它们的组合。
在一些实施方案中,本公开提供了一种用于改善皮肤中的胶原产生的方法,该方法包括施用有效量的包含重组胶原片段的组合物。
在一些实施方案中,本公开提供了一种护肤产品,该护肤产品包含本文所述的组合物,该护肤产品用于减少皱纹的出现、使肤色均匀、提供水分、减少眼下黑眼圈的出现、增加皮肤的胶原含量、增加皮肤密度、改善皮肤紧致度和弹性、改善细纹和皱纹的出现、使皮肤纹理光滑、增加皮肤光泽和亮度、改善松垂皮肤的外观、使皮肤变白或它们的任意组合。
在一些实施方案中,本文所述的组合物可以是护肤组合物,该护肤组合物可用于通过消耗作为膳食补充剂的组合物来治疗皮肤、毛发和指甲。
实施例
实施例1:渗透浓缩物的生产
经改良以表达III型重组胶原的巴斯德毕赤酵母如美国申请第16/125,386号(作为美国专利第11,028,146号发布)、美国申请第16/048,920号和美国申请第16/023,525号中所述那样制备,这些申请全文以引用方式并入本文。将改良的巴斯德毕赤酵母在摇瓶中的BMGY培养基中培养。如表1中所示补充BMGY培养基。
表1:摇瓶种子BMGY培养基组成
组分 | 在BMGY培养基中的使用率 |
1L无菌BMGY | 982 |
50mg/mL遗传霉素(Geneticin) | 10 |
99%甘油 | 10 |
将50mL制备的含有改良的巴斯德毕赤酵母的培养基接种物转移到具有0.22μmPTFE排气帽联杆的250mL带挡板的摇瓶中。将0.5mL无菌甘油原液添加到摇瓶中并将摇瓶在Infors HT Multitron Pro振荡器中以25mm的振荡器幅度在32℃和350rpm处培育23小时至26小时,直至达到15的目标OD600。摇瓶培育条件示于表2中。
表2:摇瓶种子繁殖条件
参数 | 值 |
摇瓶容积/初始发酵罐容积 | 40-50mL/L |
发酵罐目标初始OD | 0.75 |
温度 | 32C |
振荡器速度 | 350rpm |
摇动器投掷/幅度 | 25mm |
约23-26小时后的目标最终生物质密度(OD600) | 15 |
在培养达到15OD600的密度后,向发酵罐中添加40-50mL/L接种物/初始发酵培养基容积,以达到0.75的目标初始OD600。发酵培养基包括碳水化合物、氮源、盐和痕量矿物质和维生素。发酵控制在32℃,用10N氢氧化钠控制pH为6.0,且溶解氧(DO)设定点为25%饱和(基于在大气压下的氧溶解度)。在分批阶段结束时,大约25小时EFT,达到大于60的OD600和大于160g/L的细胞湿重,以10gL-1h-1(甘油克数/初始发酵罐容积)或16.67mL-1h-1(进料容积/初始发酵罐容积)的恒定速率开始60%w/v甘油进料。补料分批发酵持续至大约EFT 72小时。
离心细胞培养物并去除大约三分之二的废发酵培养基。将细胞溶解、澄清,并通过滤饼过滤和超滤去除杂质以产生渗透浓缩物。用质谱法和光谱计数测定渗透浓缩物中蛋白的量和特性。
渗透浓缩物包含约8.5重量%的重组胶原、约9.5重量%的应激相关蛋白、约6重量%的细胞壁相关蛋白、约6.5重量%的DNA或蛋白合成相关蛋白、约20重量%的代谢酶和约0.01重量%的细胞完整性蛋白。
渗透浓缩物中的应激相关蛋白包括热休克蛋白(Hsp)、硫氧还蛋白、ATP酶和蛋白质二硫键异构酶。
渗透浓缩物中的细胞壁相关蛋白包括外切-1,3-β-葡聚糖酶、内切-β-1,3-葡聚糖酶、糖苷酶、1,3-β-葡聚糖转移酶、几丁质脱乙酰酶和果糖1,6-二磷酸醛缩酶。
渗透浓缩物中的DNA或蛋白合成相关蛋白包括延伸因子1-α、腺苷激酶、60S酸性核糖体蛋白P2-A、核苷二磷酸激酶、核糖体蛋白51、核糖体蛋白L30、核糖体蛋白59、真核翻译起始因子5A、翻译起始因子elF4A、DNA拓扑异构酶2、组蛋白甲基转移酶、S-腺苷-L-甲硫氨酸依赖性tRNA、真核翻译起始因子3亚基1、赖氨酸-tRNA连接酶、DNA指导的RNA聚合酶亚基β、转录因子II和DNA连接酶。
渗透物中的代谢酶包括烯醇化酶I、磷酸丙糖异构酶、超氧化物歧化酶、甘油醛-3-磷酸脱氢酶、钴胺素非依赖性甲硫氨酸合酶、6-磷酸葡糖酸脱氢酶、磷酸转移酶、NADPH依赖性α-酮酰胺还原酶、磷酸甘油酸变位酶、细胞质无机焦磷酸酶、醇脱氢酶、羧肽酶Y抑制剂、磷脂酰甘油/磷脂酰肌醇转移蛋白、细胞质ATP酶、线粒体基质ATP酶、肽基-脯氨酰基顺反异构酶、腺苷激酶、硫醇特异性过氧化物还原酶、鸟氨酸转氨酶、酮醇酸还原异构酶、庚烯酸水合酶、苹果酸脱氢酶、甘油激酶、丙氨酸:乙醛酸转氨酶、核苷二磷酸激酶、几丁质脱乙酰酶、转酮醇酶、NADPH氧化还原酶、果糖1,6-二磷酸醛缩酶、NADH-细胞色素b5还原酶、磷酸甘露糖变位酶、线粒体过氧化物还原酶、3-异丙基苹果酸脱氢酶、硫氧还蛋白过氧化物酶、角鲨烯环氧化酶、苹果酸脱氢酶、粪卟啉原III氧化酶、异柠檬酸脱氢酶[NAD]亚基、NatB N端乙酰转移酶的催化亚基、羧肽酶、三酰基甘油脂肪酶、腺苷高半胱氨酸酶、含黄素的单加氧酶、酸性海藻糖酶、高亲和性甲硫氨酸透性酶、α-1,6甘露糖基转移酶复合体的亚基、腺苷酸环化酶、磷酸转移酶、亚甲基四氢叶酸还原酶、旁路氧化酶、Cu(+2)-转运P-型ATP酶、羧肽酶、三酰甘油脂肪酶、腺苷高半胱氨酸酶、含黄素的单加氧酶、酸性海藻糖酶、高亲和性甲硫氨酸透性酶、α-1,6甘露糖基转移酶复合物的亚基、腺苷酸环化酶、磷酸转移酶、亚甲基四氢叶酸还原酶、交替氧化酶、Cu(+2)-转运P型ATP酶、GTP酶、2-(3-氨基-3羧丙基)组氨酸合酶亚基1、过氧化物酶体生物合成蛋白PAS1、叶酰聚谷氨酸合酶、丙酮酸激酶、丝氨酸/苏氨酸蛋白磷酸酶、蛋白丝氨酸/苏氨酸激酶、β-甘露糖转移酶2、尿素酰胺水解酶、柠檬酸合酶和羊毛甾醇合酶。
实施例2:护肤组合物的生产
由实施例1生产的渗透浓缩物用于以下护肤组合物中。
面膜霜
如本文所述,通过混合表3中列出的成分来生产面膜霜。每种成分的重量百分比列于表3中,其中QS意指足以达到100重量%的量。
表3:面膜霜成分
将Solagum AH和Zemea预混成浆料。添加渗透浓缩物并将溶液混合30分钟直至发生增稠。添加Natriquest E-30并将A相加热至75℃。
将B相成分混合,然后加热至75℃以使成分融化。在混合的同时将B相缓慢添加到A相中。将溶液匀化10分钟。添加Baycusan C-1003并将溶液再匀化3分钟。在混合的同时将溶液冷却至45℃。将D相添加到溶液中并继续混合直至溶液达到室温。
将25克溶液添加到竹炭面膜中并密封在小袋中。
洗面奶
如本文所述,通过混合表4中列出的成分来生产洗面奶。每种成分的重量百分比列于表4中。
表4:洗面奶成分
将Solagum AH和Zemea预混成浆料。添加渗透浓缩物并将溶液混合30分钟直至发生增稠。添加表4中的其余成分,以便在每次添加间期充分混合。
眼部凝胶
如本文所述,通过混合表5中列出的成分来生产眼部凝胶。每种成分的重量百分比列于表5中,其中QS意指足以达到100重量%的量。
表5:眼部凝胶成分
商品名 | INCI名称 | %,范围 | %,实际值 |
渗透浓缩物 | N/A | QS | |
Zemea | 丙二醇 | 1–3 | 1.5 |
Solagum AX | 塞内加尔阿拉伯胶、黄原胶 | 0.2–1 | 0.7 |
Natraquest E-30 | 乙二胺二琥珀酸三钠 | 0.2–1 | 0.5 |
Euxyl 9010 | 苯氧乙醇.乙基己基甘油 | 0.5–1.5 | 1.0 |
将Solagum AH和Zemea预混成浆料。添加渗透浓缩物并将溶液混合30分钟直至发生增稠。添加表5中的其余成分,以便在每次添加间期充分混合。
日霜
如本文所述,通过混合表6中列出的成分来生产日霜。每种成分的重量百分比列于表6中。
表6:日霜成分
将Zemea预混成浆料。添加渗透浓缩物并混合30分钟。将Solagum AH和Zemea预混成浆料,然后添加到浆料/渗透浓缩物中。将溶液混合30分钟。添加Dermofeel PA-3并将A相加热至75℃。
将B相成分混合,然后加热至75℃以使成分融化。在混合的同时将B相缓慢添加到A相中。将溶液匀化10分钟。添加Baycusan C-1003并将溶液再匀化3分钟。在混合的同时将溶液冷却至45℃。将D相添加到溶液中并继续混合直至溶液达到室温。
咖啡擦剂
如本文所述,通过混合表7中列出的成分来生产咖啡擦剂。每种成分的重量百分比列于表7中,其中QS意指足以达到100重量%的量。
表7:咖啡擦剂成分
商品名 | INCI名称 | %,范围 | %,实际值 |
基料 | QS | 60.0 | |
咖啡粉 | 20-60 | 40.0 |
如本文所述,通过混合表8中列出的成分来生产咖啡擦剂基料。每种成分的重量百分比列于表8中。
表8:咖啡擦剂基料成分
商品名 | INCI名称 | %,范围 | %,实际值 |
渗透浓缩物 | N/A | QS | |
Zemea | 丙二醇 | 0.5–3.0 | 1.5 |
Solagum AX | 塞内加尔阿拉伯胶、黄原胶 | 0.2–1.0 | 0.7 |
Dermafeel PA-3 | 植酸钠 | 0.5–2.0 | 1.0 |
Euxyl 9010 | 苯氧乙醇.乙基己基甘油 | 0.5–1.5 | 1.0 |
将Solagum AH和Zemea预混成浆料。添加渗透浓缩物并将溶液混合30分钟直至发生增稠。添加表4中的其余成分,以便在每次添加间期充分混合。
实施例3:从培养的巴斯德毕赤酵母回收细胞内胶原
如实施例1中所述,将巴斯德毕赤酵母细胞改良为表达III型重组胶原。在生产期间,巴斯德毕赤酵母细胞将III型重组胶原直接分泌到发酵培养基中。然而,一部分重组胶原不容易分泌,并且一部分胶原留在细胞内部。因此,研究了回收细胞内胶原的方法。
在三次实验中采用来自一个巴斯德毕赤酵母批量的三个批次以确定每一批次的裂解物可回收的细胞内胶原的量。首先,从仅上清液的批次测定胶原的量和类型并用作比较因子(实验044)。第二,将整个发酵液进行细胞裂解,并进行图1流程图中所示的剩余实验方法步骤(实验023)。第三,将细胞糊浆进行细胞裂解,并进行图1流程图中所示的剩余实验方法步骤(实验027)。
如图1所示,制备0.5M磷酸氢二钠裂解缓冲溶液并用10N氢氧化钠调节至pH 9+0.05。然后,将460.2g裂解缓冲液添加到3.47kg发酵液中。用49.8g的10N氢氧化钠将混合物重新调节至pH 9,并用520.2g去离子水(DI water)稀释混合物。将裂解缓冲液、发酵液和水的混合物进料到WAB Dyno-Mill KDL 0.6珠(WAB US Corp.,Allendale,NJ)磨机中以使酵母细胞破裂。珠磨机设定为:3,200rpm,具有64mm搅拌盘,产生10.5m/s的梢速。珠粒是0.6-0.8mm氧化锆二氧化硅复合珠粒。珠磨机填充有0.48L(80%磨机容量)的珠粒。将混合物以240ml/min的进料速率进料到珠磨机中。用89.2g的50%硫酸将所得4.87kg裂解物的pH调节至pH 4.0+0.1。通过使用SORVALL离心机(Thermo Fisher Scientific,Waltham,MA)在10℃的温度处以17,000g离心20分钟来澄清裂解物。这样产生3.08kg的Sorvall离心分离液,然后使用超滤将离心分离液浓缩。Spectrum Labs Krossflow Research蠕动TFF系统(Repligen Corp.,Waltham,MA)与空心纤维mPES膜类型N06-E010-10-N过滤器,具体地10kDa MWCO膜过滤器一起使用。过滤条件为10psi TMP,流速为2880ml/min,速度为0.245m/s。使用TFF系统将3.08kg离心分离液浓缩成1.5kg浓缩渗透物。然后用1.6M硫酸钠盐溶液从溶液中沉淀出胶原片段(55kDa和50kDa片段,如图2B的实验023中所示)。将1660g的1.6M硫酸钠溶液添加到1.41kg浓缩渗透物中并混合至少20分钟。然后在20℃处使用Sorvall离心机以17,000g回收沉淀的蛋白30分钟,回收80.2g团块。将团块重悬于706.8g去离子水中。使用与上述相同的TTF系统、条件和空心纤维过滤器进行渗滤,以从产物中去除小的杂质诸如盐。渗滤用4.5渗滤体积的去离子水进行。在最后一步中,将928g渗滤产物冻干。
测量从每次实验回收的胶原。结果示于下表9中。
表9:细胞内胶原的回收
产物的比较
纯度
从实验023和实验027回收的胶原的产物纯度与实验044的产物纯度相当(如图4B所示)。
蛋白片段
所得蛋白片段通过凝胶电泳分离并进行分析。该分析在3-8%tris-乙酸盐凝胶上在恒定电压下进行1小时20分钟。将所得凝胶用胶状考马斯染料染色并用水和甲醇脱色。脱色完成后,在BioRad密度计上对凝胶进行分析。如图2A-图2C所示,最终条带之间存在明显的差异。分泌的上清液产物(实验044,图2A)显示一条胶原条带,与50kDa胶原片段(SEQ IDNO:2)相关。相反,包含细胞内胶原的实验023和实验027的产物具有2个条带。一条条带与55kDa胶原片段(SEQ ID NO:1)相关,该胶原片段是细胞内胶原,包括信号序列(SEQ ID NO:3)。(图2B和图2C)第二条带与细胞外50kDa片段(SEQ ID NO:2)相关,该片段是不含信号序列的分泌重组胶原。(图2B和图2C)假设实验27的结果仅显示细胞内55kDa条带。然而,来自实验027的细胞团块在处理之前没有彻底洗涤,并且有可能团块仍然含有一部分上清液,该部分上清液包括50kDa的片段。下面提供了每种胶原片段的氨基酸序列。
55kDa重组胶原片段(SEQ
ID
NO.1)
MYRNLIIATALTCGAYSAYVPSEPWSTLTPDASLESALKDYSQTFGIAIKSLDADKIKRDSYDVKSGVAVGGLAGYPGPAGPPGPPGPPGTSGHPGSPGSPGYQGPPGEPGQAGPSGPPGPPGAIGPSGPAGKDGESGRPGRPGERGLPGPPGIKGPAGIPGFPGMKGHRGFDGRNGEKGETGAPGLKGENGLPGENGAPGPMGPRGAPGERGRPGLPGAAGARGNDGARGSDGQPGPPGPPGTAGFPGSPGAKGEVGPAGSPGSNGAPGQRGEPGPQGHAGAQGPPGPPGINGSPGGKGEMGPAGIPGAPGLMGARGPPGPAGANGAPGLRGGAGEPGKNGAKGEPGPRGERGEAGIPGVPGAKGEDGKDGSPGEPGANGLPGAAGERGAPGFRGPAGPNGIPGEKGPAGERGAPGPAGPRGAAGEPGRDGVPGGPGMRGMPGSPGGPGSDGKPGPPGSQGESGRPGPPGPSGPRGQPGVMGFPGPKGNDGAPGKNGERGGPGGPGPQGPPGKNGETGPQGPPGPTGPGGDKGDTGPPGPQGLQGLPGTGGPPGENGKPGEPGPKGDAGAPGAPGGKGDAGAPGERGPPAIAGIGGEKAGGFAPYYG
50kDa重组胶原片段(SEQ
ID NO.2)
DVKSGVAVGGLAGYPGPAGPPGPPGPPGTSGHPGSPGSPGYQGPPGEPGQAGPSGPPGPPGAIGPSGPAGKDGESGRPGRPGERGLPGPPGIKGPAGIPGFPGMKGHRGFDGRNGEKGETGAPGLKGENGLPGENGAPGPMGPRGAPGERGRPGLPGAAGARGNDGARGSDGQPGPPGPPGTAGFPGSPGAKGEVGPAGSPGSNGAPGQRGEPGPQGHAGAQGPPGPPGINGSPGGKGEMGPAGIPGAPGLMGARGPPGPAGANGAPGLRGGAGEPGKNGAKGEPGPRGERGEAGIPGVPGAKGEDGKDGSPGEPGANGLPGAAGERGAPGFRGPAGPNGIPGEKGPAGERGAPGPAGPRGAAGEPGRDGVPGGPGMRGMPGSPGGPGSDGKPGPPGSQGESGRPGPPGPSGPRGQPGVMGFPGPKGNDGAPGKNGERGGPGGPGPQGPPGKNGETGPQGPPGPTGPGGDKGDTGPPGPQGLQGLPGTGGPPGENGKPGEPGPKGDAGAPGAPGGKGDAGAPGERGPPAIAGIGGEKAGGFAPYYG
信号序列(SEQ ID NO: 3)
MYRNLIIATALTCGAYSAYVPSEPWSTLTPDASLESALKDYSQTFGIAIKSLDADKIKRDSY
结果
结果显示,与实验027相比,使用发酵液作为原材料(实验023)允许从上清液中回收更多的胶原。在实验023和实验027中的实验方案的每个步骤回收的胶原的量是相当的,除了在裂解物澄清步骤之后的产量,对于实验023更高以外。(图3A和图3B)最高的总回收产量来自实验044(仅上清液)。从实验023、实验044回收分泌的胶原蛋白的效率较低,从实验027回收分泌的胶原蛋白的效率最低。(图4A-图4C)
实施例4:护肤组合物的生产
从实施例3生产的回收的细胞内胶原用于以下护肤组合物中。
面膜霜
如本文所述,通过混合表10中列出的成分来生产面膜霜。每种成分的重量百分比列于表10中,其中QS意指足以达到100重量%的量。
表10:面膜霜成分
洗面奶
如本文所述,通过混合表11中列出的成分来生产洗面奶。每种成分的重量百分比列于表11中。
表11:洗面奶成分
眼部凝胶
如本文所述,通过混合表12中列出的成分来生产眼部凝胶。每种成分的重量百分比列于表12中,其中QS意指足以达到100重量%的量。
表12:眼部凝胶成分
日霜
如本文所述,通过混合表13中列出的成分来生产日霜。每种成分的重量百分比列于表13中。
表13:日霜成分
咖啡擦剂
如本文所述,通过混合表14中列出的成分来生产咖啡擦剂。每种成分的重量百分比列于表14中,其中QS意指足以达到100重量%的量。
表14:咖啡擦剂成分
商品名 | INCI名称 | %,范围 | %,实际值 |
基料 | QS | 60.0 | |
咖啡粉 | 20-60 | 40.0 |
如本文所述,通过混合表15中列出的成分来生产咖啡擦剂基料。每种成分的重量百分比列于表15中。
表15:咖啡擦剂基料成分
基于醇的调色剂
通过混合表16和表17中列出的成分生产基于醇的调色剂和基于水的调色剂。
表16:基于醇的调色剂
成分: | %重量/重量 |
水(含水) | 剩余成分 |
本文公开的重组胶原片段 | 约0.0005%至约25% |
醇变性剂 | 10%-20% |
戊二醇 | 5%-10% |
甘油 | 1%-5% |
葡糖酸内酯 | 0.1%-1% |
甘草酸二钾 | 0.1%-1% |
柠檬酸钠 | 0.1%-1% |
苯甲酸钠 | 0.1%-1% |
表17:基于水的调色剂
将本文所述的组合物配制成乳霜、凝胶或精华液。示例性的乳霜、凝胶或精华液调配物如下所述。
表18:乳霜
成分: | %重量/重量 |
水(含水) | 剩余成分 |
本文公开的重组胶原片段 | 约0.0005%至约25% |
鲸蜡硬脂醇 | 5%-10% |
甘油 | 1%-5% |
角鲨烷 | 1%-5% |
牛油果树(乳木果)油 | 1%-5% |
辛酸甘油酯 | 1%-5% |
微晶纤维素 | 1%-5% |
硬脂酸柠檬酸甘油酯 | 0.1%-1% |
生育酚乙酸酯 | 0.1%-1% |
鲸蜡硬脂基葡糖苷 | 0.1%-1% |
硬脂酰谷氨酸钠 | 0.1%-1% |
纤维素胶 | 0.1%-1% |
黄原胶 | 0.1%-1% |
辛酰氧肟酸 | 0.1%-1% |
植酸钠 | 0.01%-0.1% |
表19:凝胶
成分: | %重量/重量 |
水(含水) | 剩余成分 |
本文公开的重组胶原片段 | 约0.0005%至约25% |
植酸钠 | 0.1%-1% |
氢氧化钠 | 0.1%-1% |
卡波姆 | 0.1%-1% |
苯氧乙醇 | 0.1%-1% |
表20:精华液
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将本文所述的组合物配制为洗发剂和调理剂。示例性的洗发剂或调理剂调配物如下所述。
表21:洗发剂
成分: | %重量/重量 |
水(含水) | 剩余成分 |
本文公开的重组胶原片段 | 约0.0005%至约25% |
椰油酰胺丙基甜菜碱 | 5%-10% |
月桂酰基甲基羟乙基磺酸钠 | 5%-10% |
丙二醇 | 1%-5% |
甲基油酰牛磺酸钠 | 1%-5% |
椰油基羟乙基磺酸钠 | 1%-5% |
乙二胺二琥珀酸三钠 | 0.1%-1% |
辛酰氧肟酸 | 0.1%-1% |
泛醇 | 0.1%-1% |
柠檬酸 | 0.1%-1% |
辛二醇 | 0.1%-1% |
苯甲酸钠 | 0.1%-1% |
表22:调理剂
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实施例5:在成纤维细胞中刺激胶原I和胶原III合成重组胶原片段
使用成纤维细胞培养模型来评估测试材料对胶原合成发挥作用的能力。该研究还评估了暴露于测试材料后细胞的活力。
MTT测定
细胞数目的变化可以通过MTT测定来评估。MTT测定是对细胞代谢活性的比色分析,反映了活细胞的数目。线粒体还原MTT导致不溶性紫色福尔马肼晶体的形成,用异丙醇从细胞中提取并通过分光光度法定量福尔马肼晶体。紫色的强度与细胞的代谢活性成正比并且与测试材料的毒性成反比。
将成纤维细胞接种到24孔板各个孔中的0.5ml成纤维细胞生长培养基(FGM)中,并在37±2℃和5±1% CO2处孵育过夜。第二天,通过抽吸取出培养基以消除任何非粘附细胞并更换为0.5ml新鲜FGM。细胞生长直至融合,每48小时至72小时更换一次培养基。达到融合后,用补充有1.5%FBS的DMEM处理细胞24小时,以洗去正常培养基中包含的生长因子的任何作用。在该24小时洗去期后,用溶于含1.5% FBS的FGM中的指定浓度的测试材料处理细胞。TGF-B(50ng/ml)用作诱导胶原表达的阳性对照。未处理的细胞(阴性对照)接受含1.5%FBS的DMEM。作为阴性对照,用100μM bDcAMP在含1.5% FBS的FGM中处理细胞。将细胞孵育48小时并且在孵育期结束时收集细胞培养基,并且冷冻储存(-75℃)或立即测定。材料一式三份地进行测试。
所测试的样品是本文所述的55kDa重组胶原片段(SEQ ID NO:1)、具有羟基化(7%)的全长牛胶原3(“全长bcol3”)、海洋胶原(Ashland)、阿拉伯胶原(Lipoid KosmetikAG)、重组人胶原21(Geltor)(“HumColl21”)、BIOLLAGEN(Jland Biotech)和具有羟基化(45%)的全长III型牛胶原(“全长bcol3”)。将每种胶原样品以一定百分比浓度范围稀释在含1.5%的组织培养基FGM中。在培养基中按重量计以0.1%、0.05%、0.01%、0.005%和0.001%测试55kDa重组胶原片段。在培养基中按重量计以0.05%、0.01%、0.005%、0.001%和0.0005%测试具有7%羟基化的全长III型牛胶原。在培养基中按重量计以1%、0.5%、0.01%、0.05%和0.01%测试海洋胶原。在培养基中按重量计以1%、0.5%、0.01%、0.05%和0.01%测试阿拉伯胶原。在培养基中按重量计以0.1%、0.05%、0.01%、0.005%和0.001%测试人胶原21。在培养基中按重量计以0.1%、0.05%、0.01%、0.005%和0.001%测试人胶原21。在培养基中按重量计以0.1%、0.05%、0.01%、0.005%和0.001%测试人胶原21。在培养基中按重量计以0.015%、0.003%、0.0015%、0.0003%和0.00015%测试具有45%羟基化的全长牛III型胶原。
孵育2天后,去除细胞培养基并用PBS洗涤成纤维细胞两次以去除所有剩余的测试材料。最后一次洗涤后,向每个孔中添加500μl补充有0.5mg/ml MTT的DMEM并将细胞在37±2℃和5±1% CO2处孵育1小时。孵育后,去除DMEM/MTT溶液并且再用PBS洗涤细胞一次,然后向孔中添加0.5ml异丙醇以提取紫色福尔马肼晶体。将200微升的异丙基提取物转移到96孔板中,并使用异丙醇作为空白在540nm处对该板进行读数。计算阴性对照细胞的平均MTT吸收值并用于表示100%细胞活力。然后将来自经历各种处理的细胞的单个MTT值除以阴性对照细胞的平均值,并表示为百分比以确定由每次处理引起的细胞活力的变化。
没有观察到测试的胶原会影响细胞活力。每个经过处理的细胞样品活力至少与未处理的对照细胞一样。
I型胶原测定
成纤维细胞是细胞外基质肽(包括胶原)的主要来源。前胶原(Procollagen)是由皮肤真皮层中的成纤维细胞合成的大肽,并且是胶原的前体。当前胶原被加工形成成熟的胶原蛋白时,前肽部分以I型C-肽的形式被裂解掉。然后成熟的胶原蛋白和I型C-肽片段被释放到细胞外环境中。随着胶原的合成,I型C-肽片段在组织培养基中积聚。由于在前胶原肽的两个部分之间存在1:1的化学计量比,I型C-肽的测定反映了合成的胶原的量。为了测量不同形式的胶原对胶原合成和分泌的影响,经由基于ELISA的方法测定1型C-肽。
将成纤维细胞接种到24孔板各个孔中的0.5ml成纤维细胞生长培养基(FGM)中,并在37±2℃和5±1% CO2处孵育过夜。第二天,通过抽吸取出培养基以消除任何非粘附细胞并更换为0.5ml新鲜FGM。细胞生长直至融合,每48小时至72小时更换一次培养基。达到融合后,用补充有1.5%FBS的DMEM处理细胞24小时,以洗去正常培养基中包含的生长因子的任何作用。在该24小时洗去期后,用溶于含1.5% FBS的FGM中的指定浓度的测试材料处理细胞。TGF-B(50ng/ml)用作诱导胶原表达的阳性对照。未处理的细胞(阴性对照)仅接受含1.5% FBS的DMEM。将细胞孵育48小时并且在孵育期结束时收集细胞培养基,并且冷冻储存(-75℃)或立即测定。材料一式三份地进行测试。
所测试的样品是本文所述的55kDa重组胶原片段、具有羟基化(7%)的全长牛胶原3、海洋胶原(Ashland)、阿拉伯胶原(Lipoid Kosmetik AG)、重组人胶原21(Geltor)、BIOLLAGEN(Jland Biotech)和具有羟基化(45%)的全长III型牛胶原。将每种胶原样品以一定百分比浓度范围稀释在含1.5% FBS的组织培养基FGM中(参见图11A和图11B)。在培养基中按重量计以0.1%、0.05%、0.01%、0.005%和0.001%测试本文所述的55kDa重组胶原片段(SEQ ID NO:1)。在培养基中按重量计以0.05%、0.01%、0.005%、0.001%和0.0005%测试具有7%羟基化的全长III型牛胶原。在培养基中按重量计以1%、0.5%、0.01%、0.05%和0.01%测试海洋胶原。在培养基中按重量计以1%、0.5%、0.01%、0.05%和0.01%测试阿拉伯胶原。在培养基中按重量计以0.1%、0.05%、0.01%、0.005%和0.001%测试人胶原21。在培养基中按重量计以0.1%、0.05%、0.01%、0.005%和0.001%测试人胶原21。在培养基中按重量计以0.1%、0.05%、0.01%、0.005%和0.001%测试人胶原21。在培养基中按重量计以0.015%、0.003%、0.0015%、0.0003%和0.00015%测试具有45%羟基化的全长牛III型胶原。
对于ELISA测定,制备范围0ng/ml至640ng/ml的一系列I型C-肽标准品。接下来,通过从板框中去除任何不需要的条,接着向测定中使用的每个孔中添加100μl过氧化物酶标记的抗前胶原I-C型肽抗体来制备ELISA微孔板。然后将二十(20)μl样品(收集的组织培养基)或标准品添加到适当的孔中,并将微孔板覆盖,并允许在37℃处孵育3±0.25小时。
孵育后,对孔进行抽吸并用400μl洗涤缓冲液洗涤三次。去除最后一次洗涤液后,向每个孔中添加100μl过氧化物酶底物溶液(过氧化氢+作为发色团的四甲基联苯胺),并将板在室温处孵育15±5分钟。孵育后,向每个孔中添加100μl终止液(1N硫酸),并使用微孔板读取器在450nm处对板进行读数。为了定量存在的每种物质的量,使用已知浓度的每种物质生成标准曲线。进行回归分析以建立最佳拟合这些数据点的线。使用测试材料和未处理的样品的吸光度值来估计每份样品中存在的每种物质的量。使用ANOVA比较处理平均值,每次处理n=3。统计学显著性设为p<0.05。
本文所述的55kDa重组胶原片段(SEQ ID NO:1)增加了经过处理的成纤维细胞分泌的I型胶原的量。相对于未处理的细胞,用0.1重量%(最终浓度)的55kDa人胶原片段处理使胶原I的表达增加超过200%。用相等浓度或甚至更高浓度的一系列不同胶原分别处理细胞。用与55kDa重组胶原片段相似大小或更小的一系列胶原,特别是水解的海洋胶原、阿拉伯胶原、人胶原21和BIOLLAGEN处理细胞。这些相似大小的胶原对I型胶原的产生没有影响,即使当那些胶原以55kDa片段10倍的百分比浓度进行测试时也一样。当大约7%羟化时以及当大约45%羟化时,用全长牛胶原III处理细胞。全长牛胶原III能够诱导胶原I表达,但只有当其高度羟基化(45%)时。因此,当需要增加I型胶原的产量时,包含55kDa人胶原片段的组合物是有用的。
III型胶原测定
III型胶原由真皮成纤维细胞合成为大的前肽。当肽经过加工形成成熟的III型胶原蛋白时,前肽部分被裂解掉(III型N-肽)。然后成熟的胶原蛋白和III型N-肽片段被释放到细胞外环境中。随着胶原的合成,III型N-肽片段在组织培养基中积聚。由于在前胶原肽的两个部分之间存在1:1的化学计量比,III型N-肽的测定反映了合成的胶原的量。为了测量不同形式的胶原对胶原合成和分泌的影响,经由基于ELISA的方法测定III型N-肽。
将成纤维细胞接种到24孔板各个孔中的0.5ml成纤维细胞生长培养基(FGM)中,并在37±2℃和5±1% CO2处孵育过夜。第二天,通过抽吸取出培养基以消除任何非粘附细胞并更换为0.5ml新鲜FGM。细胞生长直至融合,每48小时至72小时更换一次培养基。达到融合后,用补充有1.5%FBS的DMEM处理细胞24小时,以洗去正常培养基中包含的生长因子的任何作用。在该24小时洗去期后,用溶于含1.5% FBS的FGM中的指定浓度的下述测试材料处理细胞。TGF-B(50ng/ml)用作诱导胶原表达的阳性对照。未处理的细胞(阴性对照)仅接受含1.5% FBS的DMEM。将细胞孵育48小时并且在孵育期结束时收集细胞培养基,并且冷冻储存(-75℃)或立即测定。材料一式三份地进行测试。
所测试的样品是本文所述的55kDa重组胶原片段(SEQ ID NO:1)、具有羟基化(7%)的全长牛胶原3、海洋胶原(Ashland)、阿拉伯胶原(Lipoid Kosmetik AG)、重组人胶原21(Geltor)、BIOLLAGEN(Jland Biotech)和具有羟基化(45%)的全长III型牛胶原。将每种胶原样品以一定百分比浓度范围稀释在含1.5% FBS的组织培养基FGM中。在培养基中按重量计以0.1%、0.05%、0.01%、0.005%和0.001%测试本文所述的55kDa重组胶原片段(SEQ ID NO:1)。在培养基中以0.05%、0.01%、0.005%、0.001%和0.0005%体积测试具有7%羟基化的全长III型牛胶原。在培养基中以1%、0.5%、0.01%、0.05%和0.01%体积测试海洋胶原。在培养基中以1%、0.5%、0.01%、0.05%和0.01%体积测试阿拉伯胶原。在培养基中以0.1%、0.05%、0.01%、0.005%和0.001%体积测试人胶原21。在培养基中以0.1%、0.05%、0.01%、0.005%和0.001%体积测试人胶原21。在培养基中以0.1%、0.05%、0.01%、0.005%和0.001%体积测试人胶原21。在培养基中以0.015%、0.003%、0.0015%、0.0003%和0.00015%体积测试具有45%羟基化的全长牛III型胶原。
对于ELISA测定,制备一系列标准品并将100μl的这些标准品或样品添加到III型胶原ELISA板的孔中。然后将板在37℃处孵育1.5小时。孵育后,然后将ELISA板用洗涤缓冲液洗涤两次,接着施加100μl检测溶液。然后将ELISA板在37℃处孵育1小时。孵育后,用洗涤溶液洗涤所有ELISA板,接着添加100μl的HRP缀合物溶液,并在37℃处孵育30分钟。孵育后,再次洗涤ELISA板并向每个孔中添加100μl的底物溶液,并且将孔板在室温处孵育10分钟-30分钟,以使生色反应发生。在生色反应结束时,将100μl终止液添加到每个孔中,并且使用板读取器在460nm处对板进行读数。为了定量存在的每种物质的量,使用已知浓度的每种物质生成标准曲线。进行回归分析以建立最佳拟合这些数据点的线。使用测试材料和未处理的样品的吸光度值来估计每份样品中存在的每种物质的量。使用ANOVA比较处理平均值,每次处理n=3。统计学显著性设为p<0.05。
用一定范围的重量百分比浓度的每种胶原溶液处理细胞。结果显示,相对于未处理的细胞,用0.1%本文所述的55kDa重组胶原片段处理出乎意料地使经过处理的成纤维细胞分泌的III型胶原的量增加超过200%。因此,当需要增加III型胶原的产量时,包含55kDa人胶原片段的组合物是有用的。
对具体实施方案的以上描述将充分揭示本发明的一般性质,使得其他人可通过应用本技术领域的知识在不脱离本发明的总体构思的情况下容易地针对各种应用对此类具体实施方案进行修改和/或调整,而无需过度实验。因此,基于本文给出的教导和指导,此类调整和修改旨在在所公开实施方案的等同形式的含义和范围内。应当理解,本文的措辞或术语是出于描述的目的而不是限制的目的,使得本说明书的术语或措辞应由本领域的技术人员按照所述教导和指导来解释。
本发明的宽度和范围不应受任何上述示例性实施方案限制,而应仅按照以下权利要求书和它们的等同物来限定。
序列表
<110> 现代牧场股份有限公司(MODERN MEADOW, INC.)
<120> 护肤组合物及其使用方法
<130> 4431.061PC01
<150> US 63/146,076
<151> 2021-02-05
<160> 3
<170> PatentIn版本3.5
<210> 1
<211> 608
<212> PRT
<213> 人工序列
<220>
<223> 55kDa重组胶原片段
<400> 1
Met Tyr Arg Asn Leu Ile Ile Ala Thr Ala Leu Thr Cys Gly Ala Tyr
1 5 10 15
Ser Ala Tyr Val Pro Ser Glu Pro Trp Ser Thr Leu Thr Pro Asp Ala
20 25 30
Ser Leu Glu Ser Ala Leu Lys Asp Tyr Ser Gln Thr Phe Gly Ile Ala
35 40 45
Ile Lys Ser Leu Asp Ala Asp Lys Ile Lys Arg Asp Ser Tyr Asp Val
50 55 60
Lys Ser Gly Val Ala Val Gly Gly Leu Ala Gly Tyr Pro Gly Pro Ala
65 70 75 80
Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Thr Ser Gly His Pro Gly
85 90 95
Ser Pro Gly Ser Pro Gly Tyr Gln Gly Pro Pro Gly Glu Pro Gly Gln
100 105 110
Ala Gly Pro Ser Gly Pro Pro Gly Pro Pro Gly Ala Ile Gly Pro Ser
115 120 125
Gly Pro Ala Gly Lys Asp Gly Glu Ser Gly Arg Pro Gly Arg Pro Gly
130 135 140
Glu Arg Gly Leu Pro Gly Pro Pro Gly Ile Lys Gly Pro Ala Gly Ile
145 150 155 160
Pro Gly Phe Pro Gly Met Lys Gly His Arg Gly Phe Asp Gly Arg Asn
165 170 175
Gly Glu Lys Gly Glu Thr Gly Ala Pro Gly Leu Lys Gly Glu Asn Gly
180 185 190
Leu Pro Gly Glu Asn Gly Ala Pro Gly Pro Met Gly Pro Arg Gly Ala
195 200 205
Pro Gly Glu Arg Gly Arg Pro Gly Leu Pro Gly Ala Ala Gly Ala Arg
210 215 220
Gly Asn Asp Gly Ala Arg Gly Ser Asp Gly Gln Pro Gly Pro Pro Gly
225 230 235 240
Pro Pro Gly Thr Ala Gly Phe Pro Gly Ser Pro Gly Ala Lys Gly Glu
245 250 255
Val Gly Pro Ala Gly Ser Pro Gly Ser Asn Gly Ala Pro Gly Gln Arg
260 265 270
Gly Glu Pro Gly Pro Gln Gly His Ala Gly Ala Gln Gly Pro Pro Gly
275 280 285
Pro Pro Gly Ile Asn Gly Ser Pro Gly Gly Lys Gly Glu Met Gly Pro
290 295 300
Ala Gly Ile Pro Gly Ala Pro Gly Leu Met Gly Ala Arg Gly Pro Pro
305 310 315 320
Gly Pro Ala Gly Ala Asn Gly Ala Pro Gly Leu Arg Gly Gly Ala Gly
325 330 335
Glu Pro Gly Lys Asn Gly Ala Lys Gly Glu Pro Gly Pro Arg Gly Glu
340 345 350
Arg Gly Glu Ala Gly Ile Pro Gly Val Pro Gly Ala Lys Gly Glu Asp
355 360 365
Gly Lys Asp Gly Ser Pro Gly Glu Pro Gly Ala Asn Gly Leu Pro Gly
370 375 380
Ala Ala Gly Glu Arg Gly Ala Pro Gly Phe Arg Gly Pro Ala Gly Pro
385 390 395 400
Asn Gly Ile Pro Gly Glu Lys Gly Pro Ala Gly Glu Arg Gly Ala Pro
405 410 415
Gly Pro Ala Gly Pro Arg Gly Ala Ala Gly Glu Pro Gly Arg Asp Gly
420 425 430
Val Pro Gly Gly Pro Gly Met Arg Gly Met Pro Gly Ser Pro Gly Gly
435 440 445
Pro Gly Ser Asp Gly Lys Pro Gly Pro Pro Gly Ser Gln Gly Glu Ser
450 455 460
Gly Arg Pro Gly Pro Pro Gly Pro Ser Gly Pro Arg Gly Gln Pro Gly
465 470 475 480
Val Met Gly Phe Pro Gly Pro Lys Gly Asn Asp Gly Ala Pro Gly Lys
485 490 495
Asn Gly Glu Arg Gly Gly Pro Gly Gly Pro Gly Pro Gln Gly Pro Pro
500 505 510
Gly Lys Asn Gly Glu Thr Gly Pro Gln Gly Pro Pro Gly Pro Thr Gly
515 520 525
Pro Gly Gly Asp Lys Gly Asp Thr Gly Pro Pro Gly Pro Gln Gly Leu
530 535 540
Gln Gly Leu Pro Gly Thr Gly Gly Pro Pro Gly Glu Asn Gly Lys Pro
545 550 555 560
Gly Glu Pro Gly Pro Lys Gly Asp Ala Gly Ala Pro Gly Ala Pro Gly
565 570 575
Gly Lys Gly Asp Ala Gly Ala Pro Gly Glu Arg Gly Pro Pro Ala Ile
580 585 590
Ala Gly Ile Gly Gly Glu Lys Ala Gly Gly Phe Ala Pro Tyr Tyr Gly
595 600 605
<210> 2
<211> 546
<212> PRT
<213> 人工序列
<220>
<223> 50kDa重组胶原片段
<400> 2
Asp Val Lys Ser Gly Val Ala Val Gly Gly Leu Ala Gly Tyr Pro Gly
1 5 10 15
Pro Ala Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Thr Ser Gly His
20 25 30
Pro Gly Ser Pro Gly Ser Pro Gly Tyr Gln Gly Pro Pro Gly Glu Pro
35 40 45
Gly Gln Ala Gly Pro Ser Gly Pro Pro Gly Pro Pro Gly Ala Ile Gly
50 55 60
Pro Ser Gly Pro Ala Gly Lys Asp Gly Glu Ser Gly Arg Pro Gly Arg
65 70 75 80
Pro Gly Glu Arg Gly Leu Pro Gly Pro Pro Gly Ile Lys Gly Pro Ala
85 90 95
Gly Ile Pro Gly Phe Pro Gly Met Lys Gly His Arg Gly Phe Asp Gly
100 105 110
Arg Asn Gly Glu Lys Gly Glu Thr Gly Ala Pro Gly Leu Lys Gly Glu
115 120 125
Asn Gly Leu Pro Gly Glu Asn Gly Ala Pro Gly Pro Met Gly Pro Arg
130 135 140
Gly Ala Pro Gly Glu Arg Gly Arg Pro Gly Leu Pro Gly Ala Ala Gly
145 150 155 160
Ala Arg Gly Asn Asp Gly Ala Arg Gly Ser Asp Gly Gln Pro Gly Pro
165 170 175
Pro Gly Pro Pro Gly Thr Ala Gly Phe Pro Gly Ser Pro Gly Ala Lys
180 185 190
Gly Glu Val Gly Pro Ala Gly Ser Pro Gly Ser Asn Gly Ala Pro Gly
195 200 205
Gln Arg Gly Glu Pro Gly Pro Gln Gly His Ala Gly Ala Gln Gly Pro
210 215 220
Pro Gly Pro Pro Gly Ile Asn Gly Ser Pro Gly Gly Lys Gly Glu Met
225 230 235 240
Gly Pro Ala Gly Ile Pro Gly Ala Pro Gly Leu Met Gly Ala Arg Gly
245 250 255
Pro Pro Gly Pro Ala Gly Ala Asn Gly Ala Pro Gly Leu Arg Gly Gly
260 265 270
Ala Gly Glu Pro Gly Lys Asn Gly Ala Lys Gly Glu Pro Gly Pro Arg
275 280 285
Gly Glu Arg Gly Glu Ala Gly Ile Pro Gly Val Pro Gly Ala Lys Gly
290 295 300
Glu Asp Gly Lys Asp Gly Ser Pro Gly Glu Pro Gly Ala Asn Gly Leu
305 310 315 320
Pro Gly Ala Ala Gly Glu Arg Gly Ala Pro Gly Phe Arg Gly Pro Ala
325 330 335
Gly Pro Asn Gly Ile Pro Gly Glu Lys Gly Pro Ala Gly Glu Arg Gly
340 345 350
Ala Pro Gly Pro Ala Gly Pro Arg Gly Ala Ala Gly Glu Pro Gly Arg
355 360 365
Asp Gly Val Pro Gly Gly Pro Gly Met Arg Gly Met Pro Gly Ser Pro
370 375 380
Gly Gly Pro Gly Ser Asp Gly Lys Pro Gly Pro Pro Gly Ser Gln Gly
385 390 395 400
Glu Ser Gly Arg Pro Gly Pro Pro Gly Pro Ser Gly Pro Arg Gly Gln
405 410 415
Pro Gly Val Met Gly Phe Pro Gly Pro Lys Gly Asn Asp Gly Ala Pro
420 425 430
Gly Lys Asn Gly Glu Arg Gly Gly Pro Gly Gly Pro Gly Pro Gln Gly
435 440 445
Pro Pro Gly Lys Asn Gly Glu Thr Gly Pro Gln Gly Pro Pro Gly Pro
450 455 460
Thr Gly Pro Gly Gly Asp Lys Gly Asp Thr Gly Pro Pro Gly Pro Gln
465 470 475 480
Gly Leu Gln Gly Leu Pro Gly Thr Gly Gly Pro Pro Gly Glu Asn Gly
485 490 495
Lys Pro Gly Glu Pro Gly Pro Lys Gly Asp Ala Gly Ala Pro Gly Ala
500 505 510
Pro Gly Gly Lys Gly Asp Ala Gly Ala Pro Gly Glu Arg Gly Pro Pro
515 520 525
Ala Ile Ala Gly Ile Gly Gly Glu Lys Ala Gly Gly Phe Ala Pro Tyr
530 535 540
Tyr Gly
545
<210> 3
<211> 62
<212> PRT
<213> 人工序列
<220>
<223> 信号序列
<400> 3
Met Tyr Arg Asn Leu Ile Ile Ala Thr Ala Leu Thr Cys Gly Ala Tyr
1 5 10 15
Ser Ala Tyr Val Pro Ser Glu Pro Trp Ser Thr Leu Thr Pro Asp Ala
20 25 30
Ser Leu Glu Ser Ala Leu Lys Asp Tyr Ser Gln Thr Phe Gly Ile Ala
35 40 45
Ile Lys Ser Leu Asp Ala Asp Lys Ile Lys Arg Asp Ser Tyr
50 55 60
Claims (23)
1.一种重组胶原片段,所述重组胶原片段的分子量为约55kDa并且与SEQ ID NO:1所示的氨基酸序列具有至少约85%的序列同一性。
2.根据权利要求1所述的重组胶原片段,其中所述胶原片段具有SEQID NO:1所示的氨基酸序列。
3.一种组合物,所述组合物包含根据权利要求1或2所述的重组胶原片段。
4.根据权利要求3所述的组合物,其中所述组合物还包含具有SEQ ID NO:2所示的氨基酸序列的重组胶原片段。
5.根据权利要求3或4所述的组合物,所述组合物还包含药学上可接受的赋形剂或美容上可接受的赋形剂。
6.一种治疗皮肤病状的方法,所述方法包括将有效量的根据权利要求1或2所述的重组胶原片段局部施用于有需要的受试者。
7.一种治疗皮肤病状的方法,所述方法包括将有效量的根据权利要求4或5所述的组合物局部施用于有需要的受试者。
8.根据权利要求7所述的方法,其中所述皮肤病状选自由以下组成的组:细纹、皱纹、干性皮肤、毛孔粗大、皮肤变色、弹性降低、多余毛发、皮肤变薄、紫癜、光化性角化病、瘙痒、湿疹、痤疮、酒渣鼻、红斑、毛细管扩张、光化性毛细管扩张、皮肤癌、肥大性酒渣鼻以及它们的组合。
9.根据权利要求6至8中任一项所述的方法,其中将所述组合物局部施用于选自由以下组成的组的皮肤区域:面部表面、头皮、颈部、耳朵、肩部、胸部(包括乳房和/或领口)、手臂、手、腿、胃、臀部、腹股沟、背部、脚以及它们的组合。
10.一种产生根据权利要求1或2所述的重组胶原片段的方法,所述方法包括在遗传工程化的酵母菌株中产生所述重组胶原片段。
11.根据权利要求10所述的方法,其中所述酵母为巴斯德毕赤酵母。
12.根据权利要求10或11所述的方法,其中所述方法包括:
(i)在发酵液中发酵遗传工程化的酵母;
(ii)从所述发酵液的上清液中回收由所述遗传工程化的酵母分泌的重组胶原片段;以及
(iii)任选地,纯化所述重组胶原片段。
13.根据权利要求10或11所述的方法,其中所述方法包括:
(i)在发酵液中发酵遗传工程化的酵母;
(ii)回收所述基因工程化的酵母未分泌到所述上清液中的重组胶原片段;以及
(iii)任选地,纯化所述重组胶原片段。
14.根据权利要求13所述的方法,其中所述回收未分泌到所述上清液中的所述重组胶原片段包括从细胞糊浆回收所述细胞内的重组胶原片段。
15.根据权利要求10至15中任一项所述的方法,所述方法还包括冻干所回收的重组胶原片段。
16.一种护肤产品,所述护肤产品包含根据权利要求1或2所述的重组胶原片段,所述护肤产品用于减少皱纹的出现、使肤色均匀、提供水分、减少眼下黑眼圈的出现、增加皮肤的胶原含量、增加皮肤密度、改善皮肤紧致度和弹性、改善细纹和皱纹的出现、使皮肤纹理光滑、增加皮肤光泽和亮度、改善松垂皮肤的外观、使皮肤变白或它们的任意组合。
17.一种护肤产品,所述护肤产品包含根据权利要求3至5中任一项所述的组合物,所述护肤产品用于减少皱纹的出现、使肤色均匀、提供水分、减少眼下黑眼圈的出现、增加皮肤的胶原含量、增加皮肤密度、改善皮肤紧致度和弹性、改善细纹和皱纹的出现、使皮肤纹理光滑、增加皮肤光泽和亮度、改善松垂皮肤的外观、使皮肤变白或它们的任意组合。
18.一种治疗有需要的人类受试者的伤口的方法,所述方法包括将根据权利要求3至5中任一项所述的组合物施加于所述受试者的伤口,其中施加所述重组胶原片段诱导人I型胶原、人III型胶原或它们的组合的产生。
19.根据权利要求19所述的方法,其中所述胶原片段局部施加于所述伤口。
20.一种含水护肤组合物,所述含水护肤组合物包含水和根据权利要求1或2所述的重组胶原片段、至少一种应激相关蛋白、至少一种细胞壁相关蛋白、至少一种DNA或蛋白合成相关蛋白、至少一种代谢酶和任选的至少一种细胞完整性蛋白。
21.一种治疗皮肤区域的方法,所述方法包括向所述皮肤区域局部施加有效量的根据权利要求21所述的组合物。
22.根据权利要求22所述的方法,其中所述皮肤区域选自由以下组成的组:面部表面、头皮、颈部、耳朵、肩部、胸部(包括乳房和/或领口)、手臂、手、腿、胃、臀部、腹股沟、背部、脚以及它们的组合。
23.根据权利要求23所述的方法,其中所述面部表面选自由以下组成的组:前额、眼、口周表面、下巴表面、眶周面、鼻表面、脸颊皮肤表面以及它们的组合。
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