CN105407865A - 用于治疗皮肤屏障以及减少痤疮的包含圆叶锦葵提取物的组合物 - Google Patents
用于治疗皮肤屏障以及减少痤疮的包含圆叶锦葵提取物的组合物 Download PDFInfo
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- CN105407865A CN105407865A CN201480041715.XA CN201480041715A CN105407865A CN 105407865 A CN105407865 A CN 105407865A CN 201480041715 A CN201480041715 A CN 201480041715A CN 105407865 A CN105407865 A CN 105407865A
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Abstract
本发明公开了一种施用于患有痤疮的皮肤以治疗痤疮的组合物,所述组合物包含圆叶锦葵(Malva?neglecta)的提取物。圆叶锦葵增加了在受痤疮影响的皮肤区域处的神经酰胺产生以治疗和/或改善痤疮。另外,该组合物可包含胆固醇。
Description
相关专利申请的交叉引用
本专利申请为提交于2013年7月22日的专利申请号13/947,473和提交于2013年7月22日的专利申请号13/947,489的部分继续申请,上述两个专利申请在本专利申请中以引用方式并入本文,犹如完全在本文中阐述。
技术领域
本发明涉及用于治疗皮肤屏障和减少痤疮的包含用于皮肤上的植物提取物的组合物。更具体地,本发明涉及用于改善皮肤病症和外观的包含圆叶锦葵提取物的组合物,诸如通过改善皮肤屏障保护以及改善外观和/或抑制、减少或治疗皮肤上的痤疮的形成。
背景技术
圆叶锦葵通常被称为“野草”。原产于“旧大陆”,在整个北美中它已自然化。圆叶锦葵原产于几乎整个欧洲,从北欧(例如,丹麦、爱尔兰、挪威、瑞典、英国)、中欧(例如,奥地利、比利时)、东南欧(例如,阿尔巴尼亚、保加利亚、克罗地亚等)到西南欧(例如,法国、葡萄牙、西班牙)。它还存在于西亚、阿拉伯半岛、西北亚(例如亚美尼亚、格鲁吉亚、哈萨克斯坦、乌兹别克斯坦、蒙古)以及中国和印度次大陆。在非洲,它主要存在于北非,诸如阿尔及利亚和摩洛哥。
许多锦葵物种,包括圆叶锦葵,用于世界各地的传统医学体系中。它也已经常用作食物。它仍未作为贸易草药商业化。已知它还有各种通用名-普通锦葵、阔叶丰花草、干酪藤、干酪草、矮锦葵和圆叶锦葵(roundleafmallow)。根据未来植物(PlantsForAFuture)(http://www.pfaf.org/user/default.aspx),医学和可食用野生植物的在线数据库,圆叶锦葵被描述用作抗炎剂、消炎药、收敛剂、镇痛剂、利尿剂、润肤剂、祛痰剂、轻泻剂、泥敷剂、泻药和药膏。
未来植物(PlantsForAFuture)中公开的圆叶锦葵的用途以及其他参考文献中描述的圆叶锦葵的其他已知用途,除了用作润肤剂或药膏或泥敷剂之外,主要以摄取形式。一些传统文献也描述了用于湿疹的泥敷剂的用途。
植物或植物性药材可形成以多种方式用于局部施用的组合物。泥敷剂是软湿物质,通常是受热且含药的,其铺展在皮肤上的布料上用于治疗身体的酸痛、发炎或疼痛部分。它可在诸如切口的伤口上使用。煎剂涉及在水中煮沸植物材料以提取某些化学物质或特性。浸剂通过将植物材料浸泡在热水中(如茶包)进行制备。基于溶剂的提取通过在溶剂中碾磨或浸渍植物材料进行制备,所述溶剂通常为有机溶剂诸如醇、丙酮、己烷或氯仿。诸如未来植物及其他现有技术参考文献中所述的由植物或植物性药材形成组合物的典型传统方法,一般采用泥敷剂或煎剂或浸剂制备方法。具体地,传统技术描述了圆叶锦葵的下述形式的使用:诸如在除去植物的不溶解部分后口服的水煎剂,作为泥敷剂,或应用于烧伤、昆虫咬伤和创伤的浸剂。通过使用水,这些方法通常仅提取最极性组分,例如,单宁。
在现有技术(S.Foster和JADuke,MedicinalPlantsandHerbs,第170-171页,NewYork,HoughtonMifflinCompany2000年)中报道的圆叶锦葵的局部使用受限于创伤和肿瘤。然而,更常见的锦葵属物种,例如,欧锦葵(Malvasylvestris)有时也以煎剂或湿敷布(compress)形式延伸至圆叶锦葵,用于治疗脓肿、疖、烧伤、湿疹和昆虫咬伤。(E.Launert,TheHamlynGuidetoEdible&MedicinalPlants,第50页;D.Bown,NewEncyclopediaofHerbsandTheirUses,第270-271页,NewYork,DKPublishing,Inc.2001年)。传统文献还描述了圆叶锦葵作为用于上述医学用途的泥敷剂或煎剂的制备。当原材料伴随或不伴随加热而浸泡在水中时获得泥敷剂和煎剂,并且可涉及或可不涉及在应用前植物材料的分离。根据制备用于治疗目的的圆叶锦葵的该描述,显而易见的是最有效的制备将是这样的,其中亲水性组分,例如,单宁,在水中被提取,更多在沸水中被提取,诸如E.Launert,Edible&MedicinalPlants中所述。单宁是天然存在的植物多酚,并且是具有涩味的亲水性组分。
皮肤是身体的最大器官,并且在生物体和环境之间形成有效屏障,防止病原体入侵并抵挡化学和物理攻击,以及水和溶质的未经调节的损耗。防止过多经皮水分流失到环境的屏障的维护对所有陆生动物的生存至关重要。在哺乳动物中,这种屏障由无核、角质化、最外层表皮形成,统称为角质层。角质层(SC)当前被认为是嵌入富含脂质的细胞间基质中的富含蛋白质的角质细胞层,所谓的砖和砂浆模型(bricksandmortarmodel)。“砖(bricks)”是被角质化细胞包膜围绕的角质细胞,该角质化细胞包膜由蛋白质组成,该蛋白质主要为兜甲蛋白、丝聚蛋白和包膜素并且共价结合到脂质包膜的羟基神经酰胺分子。这些“砖”嵌入脂质双层的“砂浆(mortar)”中。所谓砂浆包含多种细胞间脂质,包括神经酰胺、游离甾醇、硫酸胆固醇(cholesterolsulphate)和游离脂肪酸。
如在Elias(“Elias”)的美国专利5,643,899中所指出,角质层脂质的细胞间、层状和双层片对功能性皮肤屏障是关键组分。Elias是指按重量计为神经酰胺(40%)、游离脂肪酸(20%-25%)和胆固醇(20%-25%)的三种主导表皮脂质。根据当前的理论,在表皮屏障中的任何干扰导致皮肤和粘膜的各种疾病和病症,诸如接触性皮炎、鱼鳞癣、牛皮癣和特应性皮炎。最近,皮肤屏障损伤已与寻常痤疮联系起来。Yamamoto等人(“Impairedwaterbarrierfunctioninacnevulgaris”,ArchDermatolRes(1995)287:214-218)描述了痤疮患者中显著降低的鞘脂类(神经酰胺和游离鞘氨醇)水平,以及降低的水屏障功能。Yamamoto已观察到对应于受损的水皮肤屏障功能的低神经酰胺水平可导致痤疮或粉刺的形成。然而,Yamamoto等人仅提及神经酰胺而未提及任何其他脂质类,诸如游离脂肪酸。基于此类观察,ThiboutotD.,DelRosso,J.Q.(2013),AcneVulgarisandtheEpidermalBarrier,SKINSTRUCTUREANDFUNCTION:TranslationofResearchtoPatientCare,6:1,第18-24页,提出表皮屏障功能异常与痤疮有关,并且受到损害的皮肤屏障还可导致复杂化寻常痤疮的外观,此类相关性对选择和确定疗程是重要的。
Elias等人描述了用于治疗患有显示出表皮增生和屏障功能破坏的皮肤或粘膜疾病或障碍的受检者的脂质和脂质制剂的应用。然而,Elias等人没有将它们的教导内容具体应用到痤疮治疗中。
发明内容
本发明涉及申请人的发现的具体实施,即仅圆叶锦葵的某些提取物或其与胆固醇的组合有利于用于施用于皮肤的局部用组合物中以及治疗受痤疮影响的皮肤的方法中,并为皮肤提供显著和意料不到的有益效果,包括增强皮肤屏障功能,以及抑制、减少和/或治疗皮肤上的痤疮的外观和形成(为简单起见,在下文仅引用为“减少痤疮的至少一个病征”,术语“减少”应理解为包括减少、抑制、治疗、延缓、改善等等)。
令人惊讶的是,发现用于改善皮肤屏障功能以及减少皮肤上痤疮的至少一个病征的有效圆叶锦葵非极性提取物使用非极性溶剂。非极性溶剂可包括选自下列的溶剂:含或不含极性改性剂的液体二氧化碳、含水乙醇、C1-C8醇(诸如甲醇、乙醇、丙醇和丁醇)、C1-C8烷烃(诸如戊烷、己烷和庚烷)、C2-C8二醇/多元醇(诸如甘油、丁二醇和丙二醇)、C5-C8环烷烃(诸如环戊烷、环己烷和环庚烷)、C1-C8烷基醚、C1-C8脂族化合物、酮、二氯甲烷、乙酸乙酯、二甲苯、甲苯、植物油、矿物油以及它们的组合。在一个优选的实施例中,使用己烷作为溶剂提取圆叶锦葵。申请人已经确定非极性提取物越多,通过向皮肤细胞施用圆叶锦葵而诱导的活性和神经酰胺产生就越高。
因此,本发明涉及用于增强皮肤屏障功能和减少痤疮的至少一个病征的包含圆叶锦葵非极性提取物的局部用组合物,以及使用该局部用组合物增强皮肤屏障功能和减少痤疮的至少一个病征的方法。在另一个实施例中,局部用组合物包含圆叶锦葵非极性提取物与胆固醇的组合,并且该方法包括此类组合物的应用。在另一个实施例中,局部用组合物基本上不含极性组分。
令人惊讶的是,还发现用于改善皮肤屏障功能以及减少皮肤上痤疮的至少一个病征的有效圆叶锦葵提取物使用圆叶锦葵的亲脂性提取物。
因此,本发明涉及用于增强皮肤屏障功能以及减少痤疮的至少一个病征的包含圆叶锦葵亲脂性提取物的局部用组合物。在另一个实施例中,所述局部用组合物包含圆叶锦葵的亲脂性提取物与胆固醇的组合,并且该方法包括此类组合物的应用。
本发明的局部用组合物同样优选包含美容上可接受的局部用载体。局部用载体可包含用于治疗圆叶锦葵被用于治疗的皮肤病症的另外的活性成分。具体地,可用于治疗痤疮或其他病症的任何另外的活性成分,此类成分优选与圆叶锦葵相容,可被包含在发明的局部用组合物中。
待局部施用于皮肤以治疗皮肤病症的圆叶锦葵提取物优选是圆叶锦葵植物的任何部分的非极性和/或亲脂性提取物。
从本发明的以下详细描述、所附权利要求中列出的本发明的范围中,本发明的这些内容和其他特征以及优点将容易地显而易见。
具体实施方式
应当理解,除非另行指出说明,本文中列出的所有百分比为基于组合物的总重量计的重量百分比。
如本文所用,“需要改善皮肤屏障功能的皮肤”非限制性地意指这样的皮肤:该皮肤缺乏水分、缺乏皮脂或具有过多的皮脂、破裂、干燥、瘙痒、鳞屑、干皮、脱水、缺乏柔软性、缺乏光泽、阴暗或缺乏脂质、具有改变的游离脂肪酸:神经酰胺:胆固醇比率、具有改变的经皮水分流失、具有改变的水屏障功能、具有改变的皮肤电导系数、表皮分化、增加的炎症/刺激性、角化过度、异常脱皮和细菌增殖。如本文所用,“需要治疗痤疮的至少一个病征的皮肤”非限制性地意指这样的皮肤,该皮肤需要:减少、抑制、治疗、延缓任何形式痤疮的诱发;和/或减少:发红、刺激性、炎症、角化过度、细菌增殖和/或异常脱皮。此外,如本文所用,“改善痤疮”(和它们的结合)被理解为减少、抑制、治疗和/或延缓任何痤疮类病症和/或任何痤疮类病症的至少一个病征的形成;和/或改善受痤疮和/或任何痤疮类病症影响的皮肤病症。
如本文所用,“美容上/皮肤病学可接受的”意指适合与组织(例如,皮肤或毛发)接触使用,而没有不适当的毒性、不相容性、不稳定性、刺激性、变应性应答等等。
如本文所用,术语“安全有效量”意指足以引起所需效果但足够低以避免严重副作用的量。化合物、提取物或组合物的安全有效量将随着例如最终使用者的年龄、健康状态和环境暴露,治疗的持续时间和性质,所采用的具体提取物、成分或组合物,以及所利用的特定药用载体和类似因素而变化。
如本文所述,申请人已发现圆叶锦葵提取物和含有其的局部用组合物提供了意料不到良好的皮肤屏障功能,并且减少、抑制、治疗和延缓任何痤疮类病症的形成。具体地,申请人已发现圆叶锦葵提取物,并且更具体地,圆叶锦葵的某些具体提取物,诱导皮肤自身的神经酰胺产生,并且此类神经酰胺诱导的产生将对减少痤疮的至少一个病征具有有益效果。
根据本发明的原理,申请人已集中于通过诱导神经酰胺的内源合成,来平衡屏障中的神经酰胺、游离脂肪酸和胆固醇水平,以达到与健康的皮肤屏障相关联的神经酰胺、游离脂肪酸和胆固醇的所需平衡,并且至少改善了痤疮。更具体地,向皮肤施用圆叶锦葵,优选圆叶锦葵的提取物,最优选圆叶锦葵的非极性提取物,诱导神经酰胺的产生。在需要改善皮肤屏障功能的皮肤中,具体地在需要治疗痤疮的至少一个病征的皮肤中,神经酰胺的水平要么太低,要么不以相对于游离脂肪酸和胆固醇的合适比例存在。圆叶锦葵,优选圆叶锦葵提取物,最优选圆叶锦葵非极性提取物的施用导致此类皮肤中神经酰胺的增加,这改善了皮肤屏障功能并改善了痤疮。
在另一个实施例中,申请人已发现圆叶锦葵提取物和包含圆叶锦葵提取物与胆固醇的组合的局部用组合物提供了意料不到良好的皮肤屏障功能并改善了痤疮。具体地,受痤疮影响的皮肤已被发现具有高水平的游离脂肪酸,具体地带有皮脂腺来源的单不饱和游离脂肪酸,这被认为是对皮肤屏障的破坏。参见MackCorreaMC1,MaoG,SaadP,FlachCR,MendelsohnR,WaltersRM,“Molecularinteractionsofplantoilcomponentswithstratumcorneumlipidscorrelatewithclinicalmeasuresofskinbarrierfunction,”ExpDermatol.(2014年1月)23(1):39-44。神经酰胺、胆固醇和游离脂肪酸为构成皮肤屏障脂质片的主要脂质。增加的游离脂肪酸,具体地皮脂腺来源的单不饱和游离脂肪酸,导致皮肤屏障的总体脂质组分的不平衡。申请人已经确定神经酰胺、胆固醇和游离脂肪酸的相对重量百分比的不平衡不利地影响了总体脂质结构和皮肤屏障的组成,并且与痤疮的发生率关联。申请人已经确定平衡受痤疮影响的皮肤中的神经酰胺、胆固醇和游离脂肪酸的量与从受影响皮肤上去除皮脂一样为有效治疗。因此,申请人已经发现,通过向受痤疮影响的皮肤施用圆叶锦葵提取物来增加内源性神经酰胺水平以诱导受影响皮肤的神经酰胺的产生,并且如上所述添加胆固醇是去除皮脂以治疗受痤疮影响的皮肤并改善痤疮的替代方案。
应当理解,另外的神经酰胺合成促进剂可与根据本发明原理的圆叶锦葵,优选圆叶锦葵提取物,最优选圆叶锦葵非极性提取物结合使用,以增加皮肤上神经酰胺的总量。合适的神经酰胺合成促进剂的例子包括但不限于裂榄种子的提取物。这些神经酰胺合成促进剂可以约0.0001%至约20%、约0.001%至约10%、约0.01%至约5%、约0.1%至约5%、或约0.2%至约2%存在于组合物中。
还应当理解,包含另外的神经酰胺,诸如,但不限于O-酰基神经酰胺和鞘氨醇代谢物和衍生物与圆叶锦葵,优选圆叶锦葵的提取物,最优选圆叶锦葵的非极性提取物结合的组合物也是本发明所预期的用于施用于需要治疗痤疮的皮肤。
根据本发明的原理,向皮肤施用包含圆叶锦葵的某些提取物的组合物以提供人皮肤细胞中的神经酰胺水平的显著增加,所述增加与改善的皮肤屏障功能相关联。如先前指出,神经酰胺:游离脂肪酸:胆固醇的比率中的任何干扰被认为是说明扰乱的屏障功能。因此,改善的皮肤屏障功能对于总体皮肤健康并且具体地对减少痤疮的至少一个病征是期望的。申请人已发现圆叶锦葵提取物的施用诱导神经酰胺的产生,并且因此有助于改善皮肤屏障功能并因此改善痤疮。此外,申请人已确定,具有皮肤脂质的适当平衡,例如,神经酰胺:游离脂肪酸:胆固醇,以实现皮肤屏障结构和具体地改善痤疮的功能的显著改善是高度期望。向有痤疮的皮肤施用提取物,优选地圆叶锦葵的某些提取物,以及任选地还有胆固醇,来支持、促进、强化且换句话讲改善(为方便起见而非旨在限制,下文中简称为“改善”)皮肤屏障健康以改善痤疮。申请人已从有痤疮的个体的皮肤测量各种皮肤脂质,并且发现受痤疮影响的个体的皮肤上的游离脂肪酸显著高于具有干净皮肤的个体的皮肤上的游离脂肪酸,如本文实例2中所示。本发明旨在通过提供圆叶锦葵提取物单独的组合或其与胆固醇的组合来平衡皮肤脂质的比率,以将皮肤屏障恢复至期望的神经酰胺:游离脂肪酸:胆固醇的相对比例。由于受痤疮影响的皮肤通常具有高水平的游离脂肪酸(例如,一些源自皮脂,并且其他来自由细菌脂肪酶水解皮脂腺甘油三酯),游离脂肪酸的添加一般来讲不认为是必须的。然而,应当理解,申请人已发现神经酰胺、游离脂肪酸和胆固醇的总体平衡在减少痤疮的至少一个病征中是重要的,使得游离脂肪酸的添加在某些情况下可认为适当。
改变的水屏障功能是破坏的皮肤屏障功能的指示(Yamamoto等人,ArchDermatolRes.,1995,287:214-218)。通过测量经皮水分流失(TEWL)和高频皮肤导电性测试评估水屏障功能。如本文实例5所述,申请人已经测量有痤疮的受检者的经皮水分流失(TEWL)和皮肤电导系数,并且注意到这些值在有痤疮的受检者中是变化的。具体地,与无痤疮的患者相比,有痤疮的患者通常具有增大的TEWL和降低的皮肤电导系数。本发明的组合物能够通过改善皮肤的神经酰胺水平,将指示皮肤屏障功能的TEWL和皮肤电导系数值恢复至在具有干净皮肤的受检者中看到的那样。本发明的组合物也能够恢复皮肤屏障功能。
可使用任何合适的制备根据本发明使用的圆叶锦葵提取物的方式。可使用常规方法获得合适提取物,所述常规方法包括但不限于通过下述方法从生物质中直接提取:研磨、浸渍、挤压、压榨、捣碎、离心,和/或以下方法诸如冷渗漉、搅拌/蒸馏、微波辅助提取、超声处理、含或不含极性改性剂的超临界/亚临界CO2压缩气体提取、加压溶剂提取、加速溶剂提取、表面活性剂辅助的加压热水提取、油提取、膜提取、索氏提取、金手指蒸馏/提取和/或例如IntegratedBotanicalTechnologies,LLC的美国专利号7,442,391、7,473,435和7,537,791(以引用的方式并入本文)中公开的方法等等,或通过其他方法诸如溶剂提取等等。具体地,根据本发明的提取物优选是通过在溶剂中研磨或浸渍植物材料而制备的基于溶剂的提取物,所述溶剂通常为有机溶剂诸如醇、丙酮、含或不含极性改性剂的液体二氧化碳、己烷或氯仿。所得的提取物主要包含非极性化合物。植物生物质优选完全由提取分离,并且在提取后不使用。
包括含水乙醇、含或不含极性改性剂的液体二氧化碳、有机溶剂、或它们中两种或更多种的组合的多种溶剂中的任一种,可用于包括溶剂提取的方法。优选地,使用非极性有机溶剂。合适的非极性有机溶剂为C1-C8烷烃,并且具体地己烷;C5-C8环烷烃;液体二氧化碳、C1-C8醇、C2-C8二醇/多元醇、C1-C8烷基醚,具体地乙醚和石油醚;包括C3-C8酮的酮、二氯甲烷、乙酸乙酯、二甲苯、甲苯、三氯甲烷、植物油、矿物油等等。具体有效,并且因此优选的溶剂包括含水乙醇、液体二氧化碳、植物油、C1-C8醇、C1-C8烷烃、C2-C8二醇/多元醇、C5-C8环烷烃以及它们的组合。在某些实施例中,使用己烷、甘油、C3-C4二醇、乙醇、含或不含极性改性剂的液体二氧化碳、氯仿或它们的组合,从圆叶锦葵根中提取非极性提取物。在某些优选的实施例中,使用己烷、乙醇、含水乙醇、或者含或不含极性改性剂的液体二氧化碳,从圆叶锦葵根中提取非极性提取物。在某些实施例中,使用己烷、甘油、C3-C4二醇、乙醇、含水乙醇、含或不含极性改性剂的液体二氧化碳、氯仿、或它们的组合,从圆叶锦葵的气生部分(地上部分,例如叶、花、苗、种子等)中提取非极性提取物。在某些优选的实施例中,使用己烷、乙醇、含水乙醇、或者含或不含极性改性剂的液体二氧化碳,从圆叶锦葵的气生部分(地上部分,例如叶、花、苗、种子等)中提取非极性提取物。在某些实施例中,使用己烷、甘油、C3-C4二醇、乙醇、含水乙醇、含或不含极性改性剂的液体二氧化碳、氯仿、或它们的组合,从圆叶锦葵全草中提取非极性提取物。在某些优选的实施例中,使用己烷、乙醇、含水乙醇、或者含或不含极性改性剂的液体二氧化碳,从圆叶锦葵全草中提取非极性提取物。应当理解,非极性提取物或化合物特征不在于偶极,而在于当溶解于非离子物质水中时是不离子化的提取物。非极性化合物还可定义为由通过化学键连接的分子构成的化合物,所述化学键以电荷的分布是对称的这样的方式排列。非极性化合物可溶解于水中,但不解离成离子,例如,非极性氨基酸。
在某些优选的实施例中,本发明的提取物是通过将圆叶锦葵原材料磨成粉并使用具有如下介电常数值的溶剂提取而制备的提取物,所述溶剂具有在20℃下介于约1和约80之间的介电常数值,优选在20℃下介于约2和约60之间的介电常数值,更优选在20℃下介于约2和约40之间的介电常数值,并且甚至更优选在20℃下介于约2和35之间的介电常数值。
申请人还已发现圆叶锦葵的亲脂性提取物和含有圆叶锦葵的亲脂性提取物的局部用组合物提供了意料不到良好的皮肤屏障保护、抑制、减少或治疗皮肤上痤疮的外观和形成。更具体地,亲脂性提取物具有亲脂性化合物,所述亲脂性化合物可作为PPAR激动剂并且因此结合到PPAR受体,这激活了具有合成神经酰胺的最终结果的级联反应。此类提取物通常由来自圆叶锦葵植物的脂质构成,并且用脂肪、油、脂质或溶剂易溶和/或易提取,所述溶剂诸如烷烃、甲苯、石油醚或者含或不含极性改性剂的液体CO2。应当理解亲脂性提取物或化合物一般来讲在水中是不可溶的,并且是对于脂质具有亲和力、趋于与脂质结合或能够在脂质中溶解的化合物。亲脂性、疏水性和非极性可描述朝向参与色散力的相同趋势,因为该术语通常可互换使用。然而,术语“亲脂性的”和“疏水性的”不是同义的,如可参见疏水性的但不亲脂性的硅氧烷和氟碳化合物。此外,尽管亲脂性和非极性提取物存在重叠,但此类提取物同样可以是排他性的。例如,非极性氨基酸实质上不是亲脂性的,并且游离脂肪酸是亲脂性化合物但不是非极性的。甾醇例如胆固醇可分类为两种。能得到非极性但非亲脂性提取物的溶剂的例子是乙酸乙酯。能得到亲脂性但非极性提取物的溶剂的例子是己烷。
在某些实施例中,组合物可包含来自圆叶锦葵所选择部分的提取物,所选择部分例如叶、苗、根、果实、花、种子或花中的一者或多者。在其他实施例中,组合物可包含来自圆叶锦葵的全草,包括叶、苗、根、果实、花和种子的提取物。另选地,组合物可包含圆叶锦葵气生部分的提取物和/或圆叶锦葵根的提取物。
本发明还包括通过向需要改善皮肤屏障功能和减少痤疮的至少一个病征的皮肤施用圆叶锦葵提取物,具体地圆叶锦葵气生部分和/或根的提取物,来改善屏障功能和改善皮肤中痤疮的至少一个病征的方法。该方法包括例如向需要改善皮肤屏障功能以改善痤疮的皮肤局部施用本发明的组合物,所述组合物包含圆叶锦葵提取物,具体地圆叶锦葵气生部分和/或根的提取物。此类局部施用可针对身体上需要治疗的任何皮肤,例如面部、唇部、颈部、胸部、背部、臂、臀部、腋窝和/或腿部的皮肤。优选地,提取物是圆叶锦葵的非极性和/或亲脂性提取物。甚至更优选地,提取物不含极性组分。圆叶锦葵的提取物优选以导致诱导神经酰胺的产生的有效量施用,以实现皮肤屏障功能的期望改善以导致痤疮改善。
本发明还包括通过向需要改善皮肤屏障功能和减少痤疮的至少一个病征的皮肤施用圆叶锦葵提取物,具体地圆叶锦葵气生部分和/或根的提取物与胆固醇的组合,来改善皮肤屏障功能和改善痤疮的方法。该方法包括,例如,向需要改善皮肤屏障功能和减少痤疮的至少一个病征的皮肤局部施用本发明的组合物,所述组合物包含圆叶锦葵提取物,具体地圆叶锦葵气生部分和/或根的提取物与胆固醇的组合。此类局部施用可针对身体上需要治疗的任何皮肤,例如面部、唇部、颈部、胸部、背部、臀部、臂、腋窝和/或腿部的皮肤。优选地,提取物是圆叶锦葵的非极性和/或亲脂性提取物。甚至更优选地,提取物不含极性组分。组合物优选以导致神经酰胺产生的期望增加的有效量施用,以导致皮肤屏障功能的改善和痤疮的至少一个病征的减少。
根据优选的实施例,本发明包括通过向需要改善皮肤屏障功能和减少痤疮的至少一个病征的皮肤施用圆叶锦葵提取物,具体地圆叶锦葵气生部分和/或根的提取物与胆固醇的组合,来改善皮肤屏障功能和改善皮肤中痤疮的至少一个病征的方法。该方法包括,例如,向需要改善皮肤屏障功能和减少痤疮的至少一个病征的皮肤局部施用本发明的组合物,所述组合物包含圆叶锦葵提取物,具体地圆叶锦葵气生部分和/或根的提取物与胆固醇的组合。此类局部施用可针对身体上需要治疗的任何皮肤,例如面部、唇部、颈部、胸部、背部、臀部、臂、腋窝和/或腿部的皮肤。优选地,提取物是圆叶锦葵的非极性和/或亲脂性提取物。组合物优选以导致神经酰胺产生的期望增加的有效量施用,以导致皮肤屏障功能的改善和痤疮的至少一个病征的减少。
任何合适量的圆叶锦葵提取物均可用于本发明的组合物中。优选地,组合物包含安全有效量的圆叶锦葵提取物。具体地,待使用的圆叶锦葵提取物的量优选选择为实现给定皮肤病症的所需治疗。例如,待用于改善皮肤屏障功能的圆叶锦葵提取物的量是基于所需实现的效果选择的。同样,待用于改善皮肤中痤疮的至少一个病征的圆叶锦葵提取物的量选择为实现所需量的改善。所有此类量通过下述确定:向皮肤施用圆叶锦葵提取物,并且观察效果直至实现所需结果,从而确定圆叶锦葵提取物的治疗有效量。在本发明的一个实施例中,根据本文所述的通过高效薄层色谱法测定神经酰胺特征图的测试(测定法5),在本发明的组合物中使用的圆叶锦葵提取物的量是有效实现神经酰胺水平增加了至少1%或更高、优选约5%或更高、更优选约10%或更高的量。在某些优选的实施例中,组合物包含大于零至约20%的圆叶锦葵提取物。在某些其他优选的实施例中,组合物包含约0.0001%至约20%、约0.0001%至约5%、约0.001%至约10%、约0.01%至约5%、约0.1%至约5%、或约0.2%至约2%的圆叶锦葵提取物。
包含圆叶锦葵的组合物在改善皮肤屏障功能中的功效可通过确认已发生神经酰胺水平增加,和通过确认已实现改善的屏障功能,诸如通过测量经皮水分流失(“TEWL”)的降低或增大的皮肤电导系数来确定。在本发明的一个实施例中,根据本文所述的通过高效薄层色谱法测定神经酰胺特征图的测试(测定法1),在本发明的组合物中使用的圆叶锦葵提取物的量是有效实现神经酰胺水平增加了至少1%或更高、优选约5%或更高、更优选约10%或更高的量。
圆叶锦葵在改善皮肤屏障功能和/或改善皮肤中痤疮的至少一个病征中的功效可通评定经皮水分流失(TEWL)和皮肤电导系数来测量。在本发明的一个实施例中,当根据本文所述的经皮水分流失(TEWL)方案(测定法2)的测定测量时,在本发明的组合物中使用的圆叶锦葵提取物的量是有效提供基线/预治疗水平之上经皮水分流失(TEWL)稳定减少了大于2-3g/m2·h、或更优选地大于5g/m2·h的量;当根据本文所述的皮肤电导系数(Skicon)程序(测定法3)测量时,在本发明的组合物中使用的圆叶锦葵提取物的量是有效提供基线/预治疗水平之上受治疗的皮肤中皮肤电导系数的任何增加的量。
在某些优选的实施例中,组合物包含大于零至约20%的圆叶锦葵提取物。在某些其他优选的实施例中,该组合物包含约0.0001%至约20%、约0.001%至约10%、约0.01%至约5%、约0.1%至约5%、或约0.2%至约2%的圆叶锦葵提取物。
任何合适的载体可用于所述组合物中。优选地,所述载体是美容上可接受的载体。如本领域的技术人员将认识到,美容上可接受的载体包括适于与身体,具体地皮肤接触使用的载体,而没有不适当的毒性、不相容性、不稳定性、刺激性、变应性应答等等。安全有效量的载体占组合物的约50%至约99.999%、优选约80%至约99.9%、更优选约99.9%至约95%、最优选约98%至约99.8%。
载体可以广泛多样的形式存在。例如,以乳液形式的载体,包括但不限于水包油、油包水、水包油包水和硅氧烷包水包油乳液可用于本文中。这些乳状液可涵盖范围较宽的粘度,例如约100厘泊至约200,000厘泊。
合适的美容上可接受的载体的例子包括用于化妆品溶液、悬浮液、洗剂、霜膏、精华液、精华素、凝胶、调色剂、棒剂、喷剂、膏剂、洗液和皂条、洗发剂、毛发调理剂、糊剂、泡沫、摩丝、粉剂、剃须膏、擦拭物、贴片、带、强力贴片、微针贴片、绷带、水凝胶、成膜产品、面膜和皮肤贴膜、粉底、液滴等等的美容上可接受的溶剂和材料。这些产品类型可包含若干类型的美容上可接受的载体,包括但不限于溶液、悬浮液、乳液诸如微乳液和纳米乳液、凝胶、固体、脂质体、其他包封技术等等。
下述是载体的非限制性例子。其他载体可由本领域的普通技术人员配制。在一个实施例中,载体包含水。在另一个实施例中,载体还可包含一种或多种含水溶剂或有机溶剂。有机溶剂的例子包括但不限于:二甲基异山梨醇;肉豆蔻酸异丙酯;阳离子、阴离子和非离子表面活性剂;植物油;矿物油;蜡;树胶;合成的和天然的胶凝剂;链烷醇;二醇;和多元醇。二醇的例子包括但不限于甘油、丙二醇、丁二醇、戊二醇、己二醇、聚乙二醇、聚丙二醇、二甘醇、三甘醇、辛二醇、甘油、丁二醇和己三醇以及它们的共聚物或混合物。链烷醇的例子包括但不限于具有约2个碳原子至约12个碳原子(例如,约2个碳原子至约4个碳原子)的那些,诸如异丙醇和乙醇。多元醇的例子包括但不限于那些具有约2个碳原子至约15个碳原子(例如,约2个碳原子至约10个碳原子)的那些,诸如丙二醇。基于载体的总重量计,有机溶剂可以约1%至约99.99%(例如,约20%至约50%)的量存在于载体中。基于载体的总重量计,水可以约5%至约95%(例如,约50%至约90%)的量存在于载体中(使用前)。溶液可包含任何合适量的溶剂,包括约40%至约99.99%。某些优选的溶液包含约50%至约99.9%、约60%至约99%、约70%至约99%、约80%至约99%、或约90%至99%的溶剂。
洗剂可由这种溶液制成。除了溶剂之外,洗剂通常包含至少一种润肤剂。洗剂可包含约1%至约20%(例如,约5%至约10%)的润肤剂和约50%至约90%(例如,约60%至约80%)的水。
可由溶液配制的另一类产品是霜膏。霜膏通常包含约5%至约50%(例如,约10%至约20%)的润肤剂和约45%至约85%(例如,约50%至约75%)的水。
还可由溶液配制的另一类产品是膏剂。膏剂可包含动物油、植物油或合成油或半固态10烃类的简单基料。膏剂可包含约2%至约10%的润肤剂和约0.1%至约2%的增稠剂。
可用于本发明的组合物还可作为乳液配制。如果载体是乳液,则约1%至约10%(例如,约2%至约5%)的载体包含乳化剂。乳化剂可为非离子、阴离子或阳离子的。
洗剂和霜膏可作为乳液配制。通常此类洗剂包含0.5%至约5%的乳化剂,而此类霜膏通常将包含约1%至约20%(例如约5%至约10%)的润肤剂;约20%至约80%(例如30%至约70%)的水;和约1%至约10%(例如约2%至约5%)的乳化剂。
水包油型和油包水型单乳液护肤制剂,诸如洗剂和霜膏,是本领域中是众所周知的,并且可用于本发明。多相乳液组合物,诸如水包油包水型或油包水包油型,也可用于本发明。通常,此类单乳液或多相乳液包含水、润肤剂和乳化剂作为主要成分。
本发明的组合物还可作为凝胶(例如,使用合适的胶凝剂的含水凝胶、醇凝胶、醇/水型凝胶或油凝胶)配制。用于含水凝胶和/或醇凝胶的合适胶凝剂包括但不限于天然树胶、丙烯酸和丙烯酸酯聚合物和共聚物以及纤维素衍生物(例如,羟甲基纤维素和羟丙基纤维素)。用于油(诸如矿物油)的合适胶凝剂包括但不限于氢化丁烯/乙烯/苯乙烯共聚物和氢化乙烯/丙烯/苯乙烯共聚物。此类凝胶通常包含介于约0.1重量%和5重量%之间的此类胶凝剂。
本发明的组合物还可配制成固体制剂(例如,基于蜡的棒剂、皂条组合物、粉剂或擦拭物)。本发明的组合物还可与固体、半固体或可溶解的基材(例如,擦拭物、面膜、垫、手套或带)组合。
本发明的组合物还可包含多种另外的美容活性剂中的任一种。合适的另外的活性剂的例子包括:亮肤剂、深色剂、另外的抗衰老剂、原弹性蛋白促进剂、胶原促进剂、抗痤疮剂、控油光剂、抗微生物剂诸如抗酵母剂、抗真菌剂和抗细菌剂、抗炎剂、抗寄生虫剂、外用止痛剂、防晒剂、光照保护剂、抗氧化剂、角质层分离剂、洗涤剂/表面活性剂、保湿剂、营养物质、维生素、能量增强剂、止汗剂、收敛剂、除臭剂、脱毛剂、毛发生长增强剂、毛发生长延缓剂、固化剂、补水剂、增效剂、抗硬结剂、皮肤调理剂、抗蜂窝炎剂、气味控制剂诸如气味遮盖剂或pH改变剂等等。
各种合适的另外美容上可接受的活性物质的例子包括羟基酸、过氧化苯甲酰、D-泛醇、UV过滤剂诸如但不限于阿伏苯宗(Parsol1789)、苯基二苯并咪唑四磺酸酯二钠(bisdisulizoledisodium)(NeoHeliopanAP)、二乙基氨基羟基苯甲酰己基苯甲酸酯(UvinulAPlus)、依莰舒(MexorylSX)、氨茴酸甲酯、4-氨基苯甲酸(PABA)、西诺沙酯、乙基己基三嗪酮(UvinulT150)、胡莫柳酯、4-甲基亚苄基樟脑(Parsol5000)、甲氧基肉桂酸辛酯(Octinoxate)、水杨酸辛酯(Octisalate)、帕地马酯O(Escalol507)、苯基苯并咪唑磺酸(Ensulizole)、聚硅氧烷-15(ParsolSLX)、三乙醇胺水杨酸盐、双-乙基乙氧苯酚甲氧基苯基三嗪(TinosorbS)、二苯甲酮1-12、二羟苯宗、甲酚曲唑三硅氧烷(MexorylXL)、二乙基己基丁酰胺基三嗪酮(UvasorbHEB)、奥克立林、氧苯酮(Eusolex4360)、舒利苯酮、2,2'-亚甲基双(4-叔辛基-6-苯并三唑苯酚)(TinosorbM)、二氧化钛、氧化锌;类胡萝卜素;自由基清除剂;自旋捕捉剂;类视色素和类视色素前体诸如30视黄醇、视黄酸和棕榈酸视黄酯;神经酰胺;多不饱和脂肪酸;必需脂肪酸;酶;酶抑制剂;矿物质;激素诸如雌激素;类固醇诸如氢化可的松;2-二甲基氨基乙醇;铜盐诸如氯化铜;含有铜的肽诸如Cu:Gly-His-Lys;辅酶Q10;氨基酸诸如脯氨酸;维生素;乳糖酸、乙酰辅酶A;烟酸;核黄素;硫胺;核糖;电子传递体诸如NADH和FADH2;和其他植物提取物(诸如燕麦、芦荟、小白菊、大豆、香菇提取物)以及它们的衍生物和混合物。
在某些优选的实施例中,护肤组合物包含圆叶锦葵提取物和至少一种另外的皮肤保湿活性剂。
在某些优选的实施例中,护肤组合物包含圆叶锦葵提取物和至少一种用于改善皮肤中痤疮的至少一个病征的另外的试剂。改善皮肤中痤疮的至少一个病征的合适的另外的试剂的例子包括但不限于抗痤疮和/或抗红斑痤疮剂。抗痤疮和抗红斑痤疮剂的例子包括但不限于:类视色素诸如维甲酸、异维甲酸、莫维A胺、阿达帕林、他佐罗汀、壬二酸和视黄醇;水杨酸;过氧化苯甲酰;间苯二酚;硫;磺乙酰胺;尿素;抗生素诸如四环素、克林霉素、甲硝唑和红霉素;抗炎剂诸如皮质类固醇(例如,氢化可的松)、布洛芬、萘普生和酮洛芬;以及咪唑类诸如酮康唑和二氯苯基咪唑二氧戊环;以及它们的盐和前药。抗痤疮活性剂的其他例子包括精油、α-红没药醇、甘草酸二钾、樟脑、β-葡聚糖、尿囊素、小白菊、类黄酮诸如大豆异黄酮、沙巴棕、螯合剂诸如EDTA、脂肪酶抑制剂诸如银和铜离子、水解植物蛋白、氯化物、碘化物、氟化物的无机离子和它们的非离子衍生物氯、碘、氟以及其他价态、合成磷脂和天然磷脂诸如ArlasilkTM磷脂CDM、SV、EFA、PLN和GLA(Uniqema,ICIGroupofCompanies,Wilton,UK)以及它们中两种或更多种的组合。
如本文所用,“原弹性蛋白促进剂”是指具有增强原弹性蛋白产生的生物活性的一类化合物。根据本发明,原弹性蛋白促进剂包括能够增强人体中原弹性蛋白的产生的所有天然或合成化合物。
合适的原弹性蛋白促进剂的例子包括但不限于黑莓提取物、黄栌提取物、小白菊提取物、珠子草提取物以及具有铜和/或锌组分的双金属络合物。具有铜和/或锌组分的双金属络合物可为,例如,柠檬酸铜-锌、草酸铜-锌、酒石酸铜-锌、苹果酸铜-锌、琥珀酸铜-锌、丙二酸铜-锌、马来酸铜-锌、天冬氨酸铜-锌、谷氨酸铜-锌、戊二酸铜-锌、富马酸铜-锌、葡糖二酸铜-锌、聚丙烯酸铜-锌、已二酸铜-锌、庚二酸铜-锌、辛二酸铜-锌、壬二酸铜-锌、癸二酸铜-锌、十二酸铜-锌或它们的组合。在一个优选的实施例中,原弹性蛋白促进剂选自黑莓提取物、黄栌提取物、小白菊提取物以及它们的组合。在一个特别优选的实施例中,原弹性蛋白促进剂选自黑莓提取物、小白菊提取物以及它们的组合。
所谓“黄栌提取物”意指“黄栌(Cotinuscoggygria)”叶的提取物,诸如其水提取物,购自BilkokoopofSofia(Bulgaria)。
所谓“黑莓提取物”意指从悬钩子(Rubus)属植物,优选地黑莓(Rubusfruticosus)分离的化合物的共混物。在一个实施例中,所述化合物分离自所述植物的花。在另一个实施例中,所述化合物分离自所述植物的干燥花。此类化合物可分离自植物的一个或多个部分(例如,整株植物、植物的花、种子、根、根茎、茎、果实和/或叶)。在一个优选的实施例中,黑莓提取物是黑莓叶提取物。一种特别合适的黑莓提取物通过用配混成约5%至约10%的活度的水和乙醇的混合物提取黑莓叶,用可从SymriseInc.(Teterboro,NJ)商购获得并且以名称“SymMatrix”销售的麦芽糖糊精基体来制备。
可采集“珠子草”的提取物并可作为整株植物使用,或任选地可使用植物的一个或多个部分(例如,植物的花、种子、根、根茎、茎、果实和/或叶)。可将珠子草植株或其部分细分成粉末,诸如通过碾磨或研磨。珠子草的合适研磨形式可从RaintreeNutrition,Inc.(CarsonCity,Nevada)商购获得。优选地,使用珠子草的低分子量级分,例如基本上不含分子量大于约100,000道尔顿的分子种类的珠子草级分。优选地,此类低分子量级分可水提取自珠子草植株。
本发明的组合物可包含美容有效量的一种或多种原弹性蛋白促进剂,诸如上文所述的那些。基于活性物质计,所述组合物优选包含约0.1%至约10%的原弹性蛋白促进剂,更优选约0.5%至约5%的原弹性蛋白促进剂,最优选约0.5%至约2%的原弹性蛋白促进剂。
如本文所用,“胶原促进剂”是指具有增强胶原产生的生物活性的化合物。根据本发明,“非类视色素胶原促进剂”包括不是类视色素或衍生自类视色素,并且能够增强人体中胶原产生的所有天然或合成化合物。
合适的胶原促进剂的例子包括但不限于如下物质:包括视黄醇、视黄醛和视黄酸的类视色素、小白菊(小白菊(Tanacetumparthenium))提取物、积雪草提取物、和豨莶草提取物;大豆提取物;胶原促进肽;乌索酸;和积雪草苷。
积雪草,在留尼汪岛上也称为紫箩(Violettemarronne),在印度称为购土可乐(GotuKola)或印度天胡葵(Indianpennywort),在北美称为积雪草R.(Centellarepanda),而在马达加斯加称为他乐婆(Talapetraka),是多形态草药,属于伞形科(Umbelliferae,Apiaceae),具体地属于天胡荽(Hydrocotyle)亚科。其在整个热带野生生长,并且喜好海拔高度约600至1200米的潮湿阴暗区域。积雪草具有三种品种:迪比卡型(Typica)积雪草、阿比西尼亚型(Abyssinica)积雪草和佛罗里达型(Floridana)积雪草。该草药是已知的并因其愈合、镇静、止痛、抗抑郁、抗病毒和抗微生物特性而被使用。该草本的生物活性看起来是由于该草本中存在三萜烯分子。合适的积雪草提取物以TECA购自BayerConsumerHealthCareofBasel(Switzerland)。
所谓“豨莶草的提取物”意指植物豨莶草的各种提取物中的任一种,包括可购自Sederma(CrodaInternationalGroupofEdison,NJ)的豨莶苷(Darutoside)。
合适的胶原促进肽包括下述matrikine肽(即,衍生自细胞外基质蛋白-胶原、弹性蛋白或蛋白聚糖的降解的肽),包括棕榈酰五肽,具体地以MATRIXYL购自Sederma(CrodaInternationalGroupofEdison,NJ)的Pal-Lys-Thr-Thr-Lys-Ser-OH;以PROCYTE购自PhotomedexofMontgomeryville(PA)的GHK铜肽;以BiopoeptideCL购自Sederma(CrodaInternationalGroupofEdison,NJ)的棕榈酰GHK肽;仿生四肽,诸如以ChronolineTriPeptide购自UnipexofQuébec(Canada)的那些;以及以Syn-Coll购自DSMofBasel(Switzerland)的棕榈酰三肽。
乌索酸也称为五环三萜酸、乌苏酸、熊果酸、乌索酸(Urson)、β-乌索酸和3-β-羟基-乌索-12-烯-28-酸。它可例如从Sigma-Aldrich(St.Louis,MO)商购获得。
积雪草苷,化学上还称为:[6-[[3,4-二羟基-6-(羟甲基)-5-(3,4,5-三羟基-6-甲基四氢吡喃-2-基)氧基四氢吡喃-2-基]氧基甲基]-3,4,5-三羟基四氢吡喃-2-基]10,11-二羟基-9-(羟甲基)-1,2,6a,6b,9,12a-六甲基-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-十四氢-1H-苉-4a-羧酸酯),例如可从BayerSantéFamilialeDivisionSerdex,69,BoulevardVictorHugo93400SAINT-OUENFrance商购获得。
本发明的组合物可包含美容有效量的一种或多种胶原促进剂。基于活性物质计,所述组合物优选包含约0.1%至约10%的胶原促进剂,更优选约0.5%至约5%的胶原促进剂,并且最优选约0.5%至约2%的胶原促进剂。
本发明的组合物还可包含至少一种亮肤活性剂。合适的亮肤活性剂的例子包括但不限于酪氨酸酶抑制剂、黑素降解剂、包括PAR-2拮抗剂的黑素体转移抑制剂、剥脱剂、防晒剂、类视色素、抗氧化剂、氨甲环酸、氨甲环酸十六烷酯盐酸盐、皮肤漂白剂、亚油酸、腺苷单磷酸二钠盐、洋甘菊提取物、尿囊素、遮光剂、滑石和二氧化硅、锌盐等等,以及Solano等人PigmentCellRes.19(550-571)和Ando等人,IntJMolSci11(2566-2575)中所描述的其他试剂。
合适的酪氨酸酶抑制剂的例子包括但不限于维生素C及其衍生物、维生素E及其衍生物、曲酸、熊果苷、间苯二酚、对苯二酚、黄酮例如甘草类黄烷、甘草根提取物、桑树根提取物、菊叶薯蓣根提取物、虎耳草提取物等等、鞣花酸、水杨酸盐和衍生物、葡糖胺和衍生物、富勒烯、扁柏酚、双酸、乙酰葡糖胺、5,5’-二丙基-联苯-2,2’-二醇(厚朴木酚素)、4-(4-羟基苯基)-2-丁醇(4-HPB),以及它们中两种或多种的组合等等。维生素C衍生物的例子包括但不限于抗坏血酸和盐、抗坏血酸-2-葡糖苷、抗坏血酸磷酸钠、抗坏血酸磷酸镁,以及富含维生素C的天然提取物。维生素E衍生物的例子包括但不限于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-生育三烯酚以及它们的混合物、生育酚乙酸酯、生育酚磷酸酯以及富含维生素E衍生物的天然提取物。间苯二酚衍生物的例子包括但不限于间苯二酚、4位取代的间苯二酚,如4-烷基间苯二酚,诸如4-丁基间苯二酚(噜忻喏(rucinol))、4-己基间苯二酚(SynoveaHR,Sytheon)、苯乙基间苯二酚(Symwhite,Symrise)、1-(2,4-二羟基苯基)-3-(2,4-二甲氧基-3-甲基苯基)-丙烷(nivitol,Unigen)等等,以及富含间苯二酚的天然提取物。水杨酸盐的例子包括但不限于4-甲氧基水杨酸钾、水杨酸、乙酰水杨酸、4-甲氧基水杨酸以及它们的盐。在某些优选的实施例中,酪氨酸酶抑制剂包括4位取代的间苯二酚、维生素C衍生物或维生素E衍生物。在更优选的实施例中,酪氨酸酶抑制剂包括苯乙基间苯二酚、4-己基间苯二酚或抗坏血酸-2-葡糖苷。
合适的黑素降解剂的例子包括但不限于过氧化物和酶,诸如过氧化物酶和木质酶。在某些优选的实施例中,黑素抑制剂包括过氧化物或木质酶。
合适的黑素体转移抑制剂的例子包括PAR-2拮抗剂,诸如大豆胰蛋白酶抑制剂或Bowman-Birk抑制剂、维生素B3和衍生物诸如烟酰胺、大豆精华、全大豆、大豆提取物。在某些优选的实施例中,黑素体转移抑制剂包括大豆提取物或烟酰胺。
剥脱剂的例子包括但不限于α-羟基酸诸如乳酸、乙醇酸、苹果酸、酒石酸、柠檬酸或前述物质的任何组合、β-羟基酸诸如水杨酸、多羟基酸诸如乳糖酸和葡萄糖酸,以及机械剥落诸如微晶换肤术。在某些优选的实施例中,剥脱剂包括乙醇酸或水杨酸。
防晒剂的例子包括但不限于阿伏苯宗(Parso1789)、苯基二苯并咪唑四磺酸酯二钠(NeoHeliopanAP)、二乙氨基羟基苯甲酰基己基苯甲酸酯(UvinulAPlus)、依莰舒(MexorylSX)、氨茴酸甲酯、4-氨基苯甲酸(PABA)、西诺沙酯、乙基己基三嗪酮(UvinulT150)、胡莫柳酯、4-甲基亚苄基樟脑(Parsol5000)、甲氧基肉桂酸辛酯(Octinoxate)、水杨酸辛酯(Octisalate)、帕地马酯O(Escalol507)、苯基苯并咪唑磺酸(Ensulizole)、聚硅氧烷-15(ParsolSLX)、三乙醇胺水杨酸盐、双乙基己氧苯酹甲氧苯基三嗪(TinosorbS)、二苯甲酮1-12、二羟苯宗、甲酚曲唑三硅氧烷(MexorylXL)、二乙基己基丁酰胺基三嗪酮(UvasorbHEB)、奥克立林、羟甲氧二苯酮(Eusolex4360)、舒利苯酮、2,2'-亚甲基双(4-叔辛基-6-苯并三唑苯酚)(TinosorbM)、二氧化钛、氧化锌等等。
类视色素的例子包括但不限于视黄醇(维生素A醇)、视黄醛(维生素A醛)、视黄醇乙酸酯、视黄醇丙酸酯、视黄醇亚油酸酯、视黄酸、视黄醇棕榈酸酯、异维甲酸、他佐罗汀、蓓萨罗丁、阿达帕林、它们中两种或更多种的组合等等。在某些优选的实施例中,类视色素选自视黄醇、视黄醛、视黄醇乙酸酯、视黄醇丙酸酯、视黄醇亚油酸酯、以及它们中两种或更多种的组合。在某些更优选的实施例中,类视色素为视黄醇。
抗氧化剂的例子包括但不限于水溶性抗氧化剂诸如巯基化合物及它们的衍生物(例如,焦亚硫酸钠和N-乙酰基半胱氨酸、谷胱甘肽)、硫辛酸和二氢硫辛酸、茋类化合物诸如白藜芦醇和衍生物、乳铁蛋白、铁和铜螯合剂以及抗坏血酸和抗坏血酸衍生物(例如,抗坏血酸-2-葡糖苷、抗坏血酸棕榈酸酯和抗坏血酸多肽)。适用于本发明组合物的油溶性抗氧化剂包括但不限于丁基化羟基甲苯、类视色素(例如,视黄醇和视黄醇棕榈酸酯)、生育酚(例如,生育酚乙酸酯)、生育三烯酚和泛醌。包含适用于本发明的组合物中的抗氧化剂的天然提取物包括但不限于:包含类黄酮和异黄酮及它们的衍生物(例如,染料木黄酮和木质素异黄酮(diadzein))的提取物、含有白藜芦醇的提取物等等。此类天然提取物的例子包括葡萄籽、绿茶、红茶、白茶、松树树皮、小白菊、不含小白菊内酯的小白菊、燕麦提取物、黑莓提取物、黄栌提取物、大豆提取物、柚提取物、麦芽精提取物、橙皮素、葡萄提取物、马齿苋提取物、甘草查耳酮、查耳酮、2,2'-二羟查耳酮、报春花提取物、蜂胶,等等。
另外的美容活性剂可以任何合适的量,例如按组合物的重量计,以约0.0001%至约20%,例如约0.001%至约10%诸如约0.01%至约5%的量存在于组合物中。在某些优选的实施例中,以0.1%至0.5%的量,而在其他优选的实施例中,1%至2%的量。
本发明的组合物可包含美容有效量的一种或多种抗炎化合物。
合适的抗炎剂的例子包括取代的间苯二酚、(E)-3-(4-甲基苯基磺酰基)-2-丙烯腈(诸如“Bay11-7082”,可从Sigma-Aldrich(St.Louis,Missouri)商购获得、四氢姜黄素(诸如四氢姜黄素CG,购自SabinsaCorporation(Piscataway,NJ)、以及来源于以下物质的提取物和材料:黄檗皮质提取物(PCE)、非变性大豆(大豆)、小白菊(Tanacetumparthenium)、姜(干姜)、银杏(银杏叶)、羟基积雪草苷(积雪草提取物成分)、黄栌(紫叶黄栌)、款冬提取物(蜂斗菜)、枸杞果(枸杞子)、水飞蓟提取物(水飞蓟)、忍冬(金银花)、秘鲁胶树(拔尔撒摩)、洋苏草(鼠尾草)、越橘提取物(红莓苔子)、苋菜油(繁穗苋)、石榴(安石榴)、马黛茶(巴拉圭冬青叶提取物)、白百合花卉提取物(白百合)、橄榄叶提取物(油橄榄)、根皮素(苹果提取物)、燕麦粉(绿燕麦)、啤酒花(蛇麻子:蛇麻种子)提取物、芒柄花P(刺芒柄花)、甘草查耳酮(甘草:胀果甘草提取物成分)、馨敏舒(红没药醇和姜提取物),它们中两种或更多种的组合等等。
在一个实施例中,抗炎剂是间苯二酚。特别合适的取代的间苯二酚包括4-己基间苯二酚和4-辛基间苯二酚,特别是4-己基间苯二酚。4-己基间苯二酚可以“SYNOVEAHR”从Sytheon(LincolnPark,NJ)商购获得。4-辛基间苯二酚可从CityChemicalLLC(WestHaven,Connecticut)商购获得。
所谓“小白菊的提取物”,其意指植物“小白菊”植株的提取物,诸如可根据标题为“PARTHENOLIDEFREEBIOACTIVEINGREDIENTSFROMFEVERFEW(TANACETUMPARTHENIUM)ANDPROCESSESFORTHEIRPRODUCTION”的美国专利申请公布号2007/0196523列出的详细内容生产。一种特别合适的小白菊提取物可以约20%活性小白菊从IntegratedBotanicalTechnologies(Ossining,NY)商购获得。
在本发明的护肤组合物中,圆叶锦葵提取物与抗炎化合物的量的比率可改变。例如,提取物和抗炎化合物可以约0.001至约100、优选约0.01至约10,更优选约0.25至约2的重量比(其通过将按干燥提取物重量计的量除以按抗炎化合物重量计的量来确定)存在。
多种其他物质也可存在于本发明的组合物中。在某些优选的实施例中,组合物包含一种或多种选自以下的局部用成分:表面活性剂、螯合剂、润肤剂、湿润剂、调理剂、防腐剂、遮光剂、芳香剂等等。
润肤剂意指帮助维持皮肤的柔软、光滑和柔韧外观的化合物(例如,通过保留在皮肤表面上或角质层中以充当润滑剂)。合适的润肤剂的例子包括存在于HandbookofCosmeticScienceandTechnology(由A.Barel,M.Paye和H.Maibach编辑,2001年由MarcelDekker,Inc(NewYork,NY)出版)中的第35章,第399-415页(GZocchi的SkinFeelAgent)的润肤剂,并且包括但不限于凡士林、己基癸基硬脂酸酯以及植物、坚果和植物油,诸如澳洲坚果油、米糠油、葡萄籽油、棕榈油、月见草油、氢化花生油和鳄梨油。
湿润剂是指旨在增加皮肤顶层的水含量的化合物(例如,吸湿化合物)。合适的湿润剂的例子包括存在于HandbookofCosmeticScienceandTechnology(由A.Barel,M.Paye和H.Maibach编辑,2001年由MarcelDekker,Inc(NewYork,NY)出版)中的第35章,第399-415页(GZocchi的SkinFeelAgent)中的那些,并且包括但不限于甘油、山梨糖醇或海藻糖(例如,α,α-海藻糖、β,β-海藻糖、α,β-海藻糖)或它们的盐或酯(例如,海藻糖6-磷酸酯)。
表面活性剂意指旨在清洗或乳化的表面活性剂。合适的表面活性剂的例子包括存在于HandbookofCosmeticScienceandTechnology(由A.Barel、M.Paye和H.Maibach编辑,2001年由MarcelDekker,Inc.(NewYork,NY)出版)中第37章,第431-450页(L.OldenhovedeGuertechin编辑的Classificationofsurfactants)中的那些,并且包括但不限于阴离子表面活性剂诸如硫酸酯、阳离子表面活性剂诸如甜菜碱、两性表面活性剂诸如椰油酰甘氨酸钠、非离子表面活性剂诸如烷基多苷。
合适的螯合剂的例子包括能够保护和保留本发明组合物的那些。优选地,所述螯合剂是乙二胺四乙酸(“EDTA”),还更优选地是乙二胺四乙酸四钠,其可以商品名“Versene100XL”从DowChemicalCompany(Midland,Michigan)商购获得。
合适的防腐剂包括,例如,对羟基苯甲酸酯、季铵类物质、苯氧基乙醇、苯甲酸盐、DMDM乙内酰脲、有机酸,并基于组合物的总重量计,以约0%至约1%或约0.05%至约0.5%的量存在于组合物中。
赋予毛发另外的属性诸如光泽的多种调理剂中的任一种适用于本发明中。例子包括但不限于具有低于约220℃的大气压沸点的挥发性硅氧烷调理剂。合适的挥发性硅氧烷的例子非排他性地包括聚二甲基硅氧烷、聚二甲基环硅氧烷、六甲基二硅氧烷、环聚二甲基硅氧烷流体诸如可以商品名“DC-345”从DowCorningCorporation(Midland,Michigan)商购获得的聚二甲基环硅氧烷,以及它们的混合物,并且优选包括环聚二甲基硅氧烷流体。其他合适的调理剂包括阳离子聚合物,所述阳离子聚合物包括聚季铵盐、阳离子瓜尔胶等等。
多种可商购获得的珠光剂或遮光剂中的任一种适用于本发明中。合适的珠光剂或遮光剂的例子包括但不限于(a)具有约16至约22个碳原子的脂肪酸和(b)乙二醇或丙二醇的单酯或二酯;(a)具有约16至约22个碳原子的脂肪酸(b)下式的聚亚烷基二醇的单酯或二酯:HO-(JO)a-H,其中J为具有约2至约3个碳原子的亚烷基基团;且a为2或3;包含约16至约22个碳原子的脂肪醇;下式的脂肪酸酯:KCOOCH2L,其中K和L独立地包含约15至约21个碳原子;不溶于洗发剂组合物中的无机固体、以及它们的混合物。
适于在皮肤上使用的任何芳香剂组合物均可根据本发明使用。
在某些优选的实施例中,本发明呈包含本发明的组合物的基材的形式。可使用任何合适的基材。例如,在美国已公布的专利申请号2005/0226834和2009/0241242中公开了合适的基材和基材材料的例子,其全文以引用的方式并入本文中。
在某些优选的实施例中,基材为擦拭物、手套或面膜。优选地,此类实施例包含水不溶性基材,此类基材如上文引用的文献中所定义。对于某些实施例,水不溶性基材可具有一定的尺寸和形状,使得它覆盖个人使用者的面部,从而有利于将水不溶性基材作为面膜基材围绕使用者的面部放置。例如,水不溶性面膜基材可具有用于使用者的嘴部、鼻部和/或眼睛配置的开口。另选地,水不溶性基材可不具此类开口。这种无开口的构造可用于本发明的实施例,其中水不溶性基材旨在覆盖在皮肤的非面部的大片区域或如果水不溶性基材旨在用作擦拭物。水不溶性基材可具有各种形状,诸如有角形状(例如矩形)或弧形形状诸如圆形或椭圆形。对于某些实施例,基材是手套,诸如描述于美国已公布的专利申请号2006/0141014的手套,其全文以引用的方式并入本文中。在本发明的一个实施例中,产品包括多个具有不同形状的水不溶性基材。
可使用向有需要的皮肤施用组合物的任何合适方法。例如,可用手从包装取出至有需要的皮肤来向有需要的皮肤直接施用组合物,或可从基材诸如擦拭物或面膜转移,或它们中两种或更多种的组合。在其他实施例中,可经由点滴器、管、滚筒、喷雾器和贴片来施用该组合物,或将该组合物加入浴槽或以其他方式加入水以待施用于皮肤等等。组合物可以多种方式/形式施用,包括但不限于作为免洗型霜膏、面膜和/或精华素。
在某些优选的实施例中,本发明的方法包括向皮肤施用仅包含圆叶锦葵提取物或其与胆固醇的组合的至少两种不同组合物或产品。例如,该方法可包括向需要改善皮肤屏障功效和减少痤疮的至少一个病征的皮肤施用仅包含圆叶锦葵提取物或其与胆固醇的组合的第一组合物,随后向需要治疗的皮肤施用不同于第一组合物的仅包含圆叶锦葵提取物或其与胆固醇的组合的第二组合物。在某些优选实施例中,第一和第二组合物可独立地选自洗剂、清洁剂、面膜、擦拭物、霜膏、精华素、凝胶等等。在某些优选的实施例中,第一组合物和第二组合物中的至少一者为清洁剂、洗剂、霜膏、精华液或精华素,而另一种为面膜或擦拭物。在某些其他优选实施例中,第一组合物和第二组合物中的至少一者为清洁剂,而另一种为洗剂或霜膏。
虽然前述说明书和附图表示本发明的示例性实施例,但应当理解,不脱离本发明的实质和范围,可对本发明做各种添加、修改和替换。具体地,本领域的技术人员应该清楚的是,不脱离本发明的实质或本质特征,本发明可以以其他具体形式、结构、布置、比例,以及用其他要素、材料和部件来实施。本领域的技术人员应当理解,本发明可与在本发明的实践中使用的结构、布置、比例、材料和部件等的许多修改形式一起使用,这些修改形式尤其能够适用于具体环境和操作要求,而不脱离本发明的原理。因此,当前公开的实施例在各方面被认为是例示性的而非限制性的,本发明的范围由所附权利要求书指出,并不受前述描述的限制。应当理解在权利要求中,术语“包括/包括的”不排除其他要素或步骤。此外,单数形式的引用不排除复数。术语“一个(a)”、“一种(an)”“第一”、“第二”等不排除复数。
实例
下述测试方法用于实例中。
测定法1:通过高效薄层色谱法测定神经酰胺特征图色谱法
样品提取和浓缩
皮肤等同物或0.5-1×106细胞用2mL氯仿:甲醇(2:1)匀化,并转移至包含1mL磷酸盐缓冲盐水溶液的小瓶。匀化器用两个连续的2mL份的氯仿:甲醇(2:1)冲洗,并且将冲洗液加入包含提取物和PBS的小瓶。将混合物涡旋并允许相分离。使有机相在真空下蒸发至干燥。使样品残渣溶解于200μL氯仿:甲醇(2:1)中。
高效薄层色谱法
将残渣溶解于200μL氯仿:甲醇(2:1)中。使用CAMAG自动TLC采样器4,将二十(20)微升和四十(40)uL的样品溶液施涂于HPTLC板(WhatmanPartisil)上,并使用下述顺序发展体系进行分离:(1)二氯甲烷:乙酸乙酯:丙酮(80:16:4),(2)氯仿:甲醇:丙酮(76:16:8),和(3)己烷:氯仿:乙酸:丙酮:甲醇(6:80:0.1:10:4)。用溶于8%磷酸中的3%乙酸铜将板染色并在160℃下炭化。
定量
平行地施涂样品以校正位置并与类似地制备的空白提取物(未暴露于皮肤脂质的胶带条)比较。通过密度测定法(CAMAG)针对已知量的神经酰胺III标准物(Cosmoferm)进行定量。
测定法2:经皮水分流失(TEWL)的测定
开放室蒸发器用于测量经皮水分流失(TEWL),其提供在干净皮肤(对照)和痤疮皮肤的受检者中的皮肤屏障功能的估计。针对这些测量,将探针与皮肤表面轻轻地接触放置。在估计过程中要求受检者躺下,并且保持探针水平;每次测量消耗约1分钟。在前额上的测量在施用擦拭前额之前进行(是CUDERM公司的注册商标(12221MeritDr.,Suite940,Dallas,TX75251USA)。
测定法3:皮肤电导系数的测定(Skicon)
Skicon200EX仪器(由IBSLtd.(Hamamatsu,Japan)制造)用于测量皮肤表面的电导系数,这有助于提供干净皮肤(对照)和痤疮皮肤的受检者中的皮肤水含量的测量。针对这些测量,将探针与皮肤表面轻轻地接触放置。在前额上的测量在施用擦拭前额之前进行。
测定法4:表皮脂质的测定
Leukoflex胶带用于胶带剥离皮肤,用于经由HPTLC高效薄层色谱法在具有干净皮肤(对照组)和痤疮皮肤(测试组)的受检者中分析表皮脂质。按如下进行胶带剥离方案:
1.当处理Leukoflex胶带时,研究人员一直戴着手套以防止对胶带可能的污染。未使用的胶带保持在保护套内的平坦表面上,以防止胶带脱落它们的背衬。
2.将胶带预切成圆形(~3.5cm直径)。使用镊子将胶带从背衬除去并尽可能绷紧地施用于测试区域。
3.通过滚动小木辊或一个戴手套的手指(一次)跨过胶带来确保胶带的平稳接触。
4.在施用后60秒,使用镊子除去胶带。
5.将胶带插入20mL玻璃闪烁小瓶中(以尽可能好地避免胶带自身折叠)。
6.将样品保存在-80℃下直到分析或装载。
测定法5:皮脂腺脂质的测定
根据下面的过程,粘合剂贴片用于估计皮脂恢复(即在给定时期中产生的皮脂量):
1.使受检者适应室内条件[原理证明(POP)实验室]约30分钟,每次访问在一天的约相同的时间进行以避免昼夜节律影响。
2.测试区域(前额)用酒精棉(BD70%IPA–即,BectonDickinson异丙醇棉)擦拭十次以除去任何皮脂/碎片/汗液/产物等。相同技术用于每个受检者/时间点。以水平方式,将该区域从左到右擦拭5次,将擦拭物翻转过来,并且然后从右到左擦拭该区域5次,确保覆盖整个取样区。
3.使测试区域干燥至少一分钟。
4.研究人员一直戴着手套以防止来自指尖的油对Sebutapes可能的污染。利用边缘平滑的镊子,将2个CuDermSebutape粘合剂贴片牢固地以垂直方向施用于测试区域,其中一条胶带置于靠近面部中心的任一眉毛上。通过在每个胶带上滚动戴手套的手指将胶带牢固地按压到位。
5.在受检者被要求呆在POP室或接近仪器室(其被设定相同的温度/湿度)的过程中,时间设定为30分钟。
6.在30分钟采油期之后,使用镊子除去胶带,并且将胶带施用于Sebutape卡用于图像分析。
7.第二组胶带被施用在与原来的胶带(轮廓保持来自第一组)在步骤4中在相同的位置上。
8.在受检者被要求呆在POP室或接近仪器室(其被设定相同的温度/湿度)的过程中,时间设定为30分钟。
9.30分钟后,使用镊子除去胶带。
10.将来自第二组的胶带直接置于20mL闪烁小瓶中,并且保持在冰上直到它们保存在-80℃冷冻机中用于通过HPTLC分离的后续脂质分析和通过GC-FID(气相色谱法-火焰离子化检测)的进一步量化。
注意:所有的胶带(在卡上和在小瓶中)都是根据受检者编号、时间点和受检者前额的位置来标记的(参见附件III,其中左/右定义为受检者的左/右侧)。
测定法6:基因表达
使用含DNaseI消化的QiagenRNeasy试剂盒(目录#79254)(Valencia,CA),从已用溶解于DMSO(二甲基亚砜)中的提取物或不含提取物的DMSO(作为对照)处理24小时的原代人角质细胞和皮肤等同物中分离样品。使用高容量cDNA试剂盒(生命技术(Lifetechnologies)目录#4368814)进行逆转录。
40至60ngcDNA样品用于QPCR(定量聚合酶链反应)。Taqman基因表达测定法购自LifeTechnologies(GrandIsland,NY)。使用Applied制造的ABI7500快速放大器进行QPCR反应。使用的PCR引物呈现于表1。所有基因表达数据通过参考基因,聚合酶(RNA)II多肽A(POLR2A)或/和核糖体蛋白,大型,PO(RPLPO)进行归一化。通过比较CT法计算相对基因表达。
鞘磷脂磷酸二酯酶3是人体中由SMPD3基因编码的酶,并且涉及神经酰胺合成。神经酰胺葡萄糖基转移酶(UGCG)将神经酰胺转化为葡萄糖基神经酰胺以用于传递。非常长的链脂肪酸合成需要非常长的链脂肪酸4(ELOVL4)的伸长,这些脂肪酸是神经酰胺的主要组分。
表1-PCR引物
下述实例示出了圆叶锦葵提取物的制备和功效。
实例1:由气生部分制备圆叶锦葵提取物(E1)
圆叶锦葵植株在纽约进行野外采集。物种鉴定基于肉眼形态特征[Gleason&Cronquist,ManualofVascularPlants;DVanNostrandCompany,NY:第462-463页]。将植物清掉土壤和碎片,并且分离成气生部分和根。使约80g新鲜的气生植物材料与200mL80%含水甲醇一起在共混机中匀化;使悬浮液维持恒速运动24小时。然后在低压下使用不超过40℃的旋转蒸发器过滤和干燥所得的悬浮液。过滤后,如上所述再次提取剩下的原材料。合并的来自两次提取的干物质指定为粗提物,约2.1g,6.6%的收率。将粗提物重悬浮于100mL水中,并且使用三等份己烷在分液漏斗中进行液液溶剂分配。将三份己烷合并,并使用不超过40℃的旋转蒸发器在低压下进行干燥,以获得约200mg的总质量(E1),0.6%的收率。
实例2:表皮脂质和皮脂脂质的估计
分别使用测定法4和测定法5的方法测量在有痤疮皮肤的受检者中的表皮脂质和皮脂脂质,结果在下方图1和2中绘出。
图1-表皮脂质的估计
图2-皮脂脂质的估计
其中
α:p<0.05痤疮组对干净组
β:p<0.10痤疮组对干净组
从上图可以看出,在表皮脂质或表面脂质中,游离脂肪酸类在痤疮组比在对照干净皮肤组高得多。在皮脂中的游离脂肪酸在痤疮受检者中也高于干净皮肤受检者。所有皮脂腺脂质类在痤疮受检者中比例较高。
实例3:人原代角质细胞中神经酰胺的测定
使用上述测定法1的方法,测试提取物E1的神经酰胺水平。结果在下表2中给出。
表2:在角质细胞培养模型中的神经酰胺产生的结果
提取物 | 浓度(μg/mL) | 对照百分比 |
载体 | 0.1%DMSO | 100 |
E1 | 25 | 124 |
实例4:神经酰胺合成基因的转录
根据上文所描述的测定法6的方法测试提取物E1的神经酰胺合成基因转录的增加,并且结果在下表3中给出。
表3:使用人角质细胞培养物的PCR实验结果,其示出关于神经酰胺 合成和转运基因的结果。
实例5:表皮脂质水平与痤疮严重程度的相关性
下图示出高神经酰胺与较低痤疮分数关联,并且反之亦然。由皮肤科医生确定痤疮严重程度分数。每月的变化反映影响皮肤的季节变化:
图3-神经酰胺水平与痤疮严重程度的相关性
实例6:皮肤屏障功能的测定
分别通过使用测定法2和3的方法,测定经皮水分流失(TEWL)和皮肤电导系数来测量皮肤屏障功能。结果分别在图4和图5中绘出。
图4-痤疮受检者的经皮水分流失(TEWL)
图5-痤疮受检者的皮肤电导系数
其中
*:p<0.05对00(2011年12月)
p<0.10对00(2011年12月)
α:p<0.05痤疮组对干净组
β:p<0.10痤疮组对干净组
如从图4可看出,在每月一次测量的整个12个连续月的周期中(00-12个月),在与干净组进行比较时,TEWL的水平在痤疮组中显著较高。两组中观察到的水平的波动与季节变化关联。图5示出在06-09的夏季月份中观察到的在具有较高差异的干净组中的较高皮肤电导系数水平。
神经酰胺是皮肤的脂质组分,其是皮肤外层的重要部分,并且因此在保护皮肤的屏障功能中是重要的。神经酰胺水平与痤疮发展严重程度的相关性示于实例8中,在显示出较低痤疮等级的皮肤中具有较高水平的神经酰胺。在痤疮受检者中屏障功能的损伤示于实例5中,其中痤疮受检者的皮肤具有比具有干净皮肤的受检者高的TEWL值和低的皮肤电导系数。先前实例6-实例7证实圆叶锦葵的非极性提取物(E1)诱导神经酰胺合成和转运基因表达,以及在功能上增加神经酰胺的内源产生的能力。
总之,这些变化指示圆叶锦葵的非极性提取物(E1)具有诱导生理变化的能力,所述生理变化正向影响皮肤屏障功能,并改善痤疮的至少一个病征的外观。通过增加神经酰胺和皮肤脂质的产生,圆叶锦葵提取物将有望恢复神经酰胺:游离脂肪酸:胆固醇的比率,并且因此强化皮肤屏障,从而导致改善痤疮的至少一个病征的外观。
Claims (15)
1.一种组合物,所述组合物包含圆叶锦葵的非极性提取物或亲脂性提取物或非极性亲脂性提取物、胆固醇以及美容上可接受的局部用载体。
2.根据权利要求1所述的组合物,其还包含用于减少痤疮的至少一个病征的活性剂。
3.根据权利要求1所述的组合物,其中所述局部用组合物包含约0.001%至约90%的圆叶锦葵的提取物。
4.根据权利要求1所述的组合物,其中所述局部用组合物包含约0.01重量%至约20重量%的所述圆叶锦葵草药的提取物。
5.根据权利要求1所述的组合物,其中所述局部用组合物包含约0.01%至约5%的所述圆叶锦葵的提取物。
6.根据权利要求1所述的组合物,其中所述组合物包含约0.01%至约2%的所述圆叶锦葵的提取物。
7.根据权利要求1所述的组合物,其还包含另外的神经酰胺产生诱导剂。
8.根据权利要求7所述的组合物,其中所述神经酰胺产生诱导剂为裂榄(Burserasimaruba)。
9.根据权利要求8所述的组合物,其中所述神经酰胺产生诱导剂为裂榄种子的提取物。
10.根据权利要求7所述的组合物,其中所述神经酰胺产生诱导剂以足以诱导神经酰胺产生的量存在。
11.根据权利要求1所述的组合物,其中所述组合物还包含游离脂肪酸。
12.根据权利要求1所述的组合物,其中所述提取物包含圆叶锦葵的非极性提取物或亲脂性提取物或非极性亲脂性提取物。
13.根据权利要求12所述的组合物,其中所述提取物为非极性提取物。
14.根据权利要求13所述的组合物,其中所述提取物基本上不含极性组分。
15.根据权利要求1所述的组合物,其中所述提取物为己烷提取物。
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CN201480041715.XA Pending CN105407865A (zh) | 2013-07-22 | 2014-07-22 | 用于治疗皮肤屏障以及减少痤疮的包含圆叶锦葵提取物的组合物 |
CN201480041713.0A Pending CN105407864A (zh) | 2013-07-22 | 2014-07-22 | 利用圆叶锦葵提取物治疗皮肤屏障以及减少痤疮的方法 |
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CN201480041713.0A Pending CN105407864A (zh) | 2013-07-22 | 2014-07-22 | 利用圆叶锦葵提取物治疗皮肤屏障以及减少痤疮的方法 |
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EP (3) | EP2829303A1 (zh) |
KR (2) | KR20160034371A (zh) |
CN (2) | CN105407865A (zh) |
AU (2) | AU2014293311A1 (zh) |
CA (2) | CA2916379A1 (zh) |
RU (2) | RU2016105743A (zh) |
WO (2) | WO2015013286A1 (zh) |
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KR101978716B1 (ko) * | 2017-12-19 | 2019-05-15 | 이강태 | 천연 식물 추출물과 pha를 함유하는 피부 여드름 개선용 화장료 조성물 |
EP4059508A1 (en) * | 2021-03-19 | 2022-09-21 | Johnson & Johnson Consumer Inc. | Methods of using compositions comprising an iceland moss extract |
KR20220155045A (ko) | 2021-05-14 | 2022-11-22 | 임해연 | 자동 삼각대 |
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FR2790669B3 (fr) * | 1999-03-11 | 2001-04-20 | Maurice Vestri | Composition a base de plantes a usage externe, notamment pour le traitement des plaies, et utilisation |
KR19990078610A (ko) * | 1999-07-03 | 1999-11-05 | 김현준 | 피부보호용조성물 |
FR2814070B1 (fr) * | 2000-09-20 | 2002-12-13 | Silab Sa | Procede d'extraction d'un principe actif a base de malva sylvestris, principe actif obtenu et traitement cosmetique l'utilisant |
US7442391B2 (en) | 2002-01-25 | 2008-10-28 | Integrated Botanical Technologies, Llc | Bioactive botanical cosmetic compositions and processes for their production |
JP5276270B2 (ja) | 2004-01-12 | 2013-08-28 | アクゾ ノーベル サーフェイス ケミストリー リミテッド ライアビリティ カンパニー | ツバキ科植物に由来する生理活性組成物ならびにそれらを生成および使用するための工程 |
US7452547B2 (en) | 2004-03-31 | 2008-11-18 | Johnson&Johnson Consumer Co., Inc. | Product for treating the skin comprising a polyamine microcapsule wall and a skin lightening agent |
US20060088615A1 (en) * | 2004-10-26 | 2006-04-27 | Miri Seiberg | Compositions containing Malva sylvestris extract and use thereof on skin and mucosal tissues |
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2014
- 2014-07-21 EP EP14177903.3A patent/EP2829303A1/en not_active Withdrawn
- 2014-07-22 CN CN201480041715.XA patent/CN105407865A/zh active Pending
- 2014-07-22 WO PCT/US2014/047634 patent/WO2015013286A1/en active Application Filing
- 2014-07-22 CA CA2916379A patent/CA2916379A1/en not_active Abandoned
- 2014-07-22 EP EP14750647.1A patent/EP3024436A1/en not_active Withdrawn
- 2014-07-22 CN CN201480041713.0A patent/CN105407864A/zh active Pending
- 2014-07-22 AU AU2014293311A patent/AU2014293311A1/en not_active Abandoned
- 2014-07-22 WO PCT/US2014/047630 patent/WO2015013282A1/en active Application Filing
- 2014-07-22 KR KR1020167004442A patent/KR20160034371A/ko not_active Application Discontinuation
- 2014-07-22 AU AU2014293315A patent/AU2014293315A1/en not_active Abandoned
- 2014-07-22 EP EP14750271.0A patent/EP3024435A1/en not_active Withdrawn
- 2014-07-22 RU RU2016105743A patent/RU2016105743A/ru not_active Application Discontinuation
- 2014-07-22 CA CA2916724A patent/CA2916724A1/en not_active Abandoned
- 2014-07-22 RU RU2016105476A patent/RU2016105476A/ru not_active Application Discontinuation
- 2014-07-22 KR KR1020167004443A patent/KR20160033216A/ko not_active Application Discontinuation
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Also Published As
Publication number | Publication date |
---|---|
RU2016105743A (ru) | 2017-08-29 |
KR20160033216A (ko) | 2016-03-25 |
CN105407864A (zh) | 2016-03-16 |
WO2015013282A1 (en) | 2015-01-29 |
CA2916724A1 (en) | 2015-01-29 |
RU2016105476A (ru) | 2017-08-29 |
EP3024435A1 (en) | 2016-06-01 |
WO2015013286A1 (en) | 2015-01-29 |
EP3024436A1 (en) | 2016-06-01 |
AU2014293315A1 (en) | 2016-01-07 |
EP2829303A1 (en) | 2015-01-28 |
AU2014293311A1 (en) | 2016-01-07 |
KR20160034371A (ko) | 2016-03-29 |
CA2916379A1 (en) | 2015-01-29 |
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