CN103961278A - 包括卡卡杜李提取物或巴西莓提取物的组合物 - Google Patents
包括卡卡杜李提取物或巴西莓提取物的组合物 Download PDFInfo
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Abstract
本发明公开了一种包含卡卡杜李提取物或巴西莓提取物或二者的组合的局部护肤组合物。所述组合物可以包括高的氧自由基吸收能力(ORAC)值。所述组合物能够改善皮肤的视觉外观、生理功能、临床性质和/或生物物理性质。
Description
本申请是申请日为2007年1月19日、申请人为玫琳凯有限公司、发明名称为“包括卡卡杜李提取物或巴西莓提取物的组合物”的中国专利申请200780002745.X的分案申请。
相关申请的交叉引用
本申请要求2006年1月19日提交的美国临时专利序列号60/760,103、2006年1月20日提交的美国临时专利序列号60/760,977和2006年1月20日提交的美国临时专利序列号60/760,979的权益。这些申请的内容通过引用被包括在此。
技术领域
本发明涉及能够被用于改善皮肤视觉外观的组合物。具体地说,本发明涉及包含卡卡杜李(Terminalia ferdinandiana)提取物和/或巴西莓(Euterpe oleracea)提取物的局部护肤组合物。
背景技术
随着老化,慢性曝露于不利的环境因素或营养不良,皮肤的视觉外观、物理性质和生理功能可能以被认为视觉不期望的方式变化。最显著的和明显的变化包括细线和皱纹的发展、弹性的丧失、松垂的增加、结实的丧失、色泽均匀性或色调的丧失、粗糙的表面肌理和斑驳的色素沉着(mottledpigmentation)。由于皮肤老化或持续慢性的环境损害(environmental insults)而产生的较不明显的但可测量的变化,包括细胞和组织活力的一般减少、细胞复制速率的降低、减小的皮肤血流量、减小的含水量、结构和功能累积的错误、一般生物化学途径的正常调节的改变和皮肤的重新塑造和自身修复能力的减小。皮肤外观和功能的许多改变是由皮肤的外部表皮层的改变造成的,而其它的改变则由较低的真皮的变化引起。
几种不同的方法已经被用于治疗由老化、环境因素、化学品或营养不良造成的损害皮肤。一种方法涉及使用具体药剂直接刺激或抑制所选择的生化靶。例子包括使用类维生素A(retinoids)以刺激成纤维细胞的胶原和葡糖胺聚糖(glycosaminoglycan)的合成(Schiltz等,1986)。另一个方法是用刺激表皮自身取代速率的试剂或方法,称为表皮细胞更新的方法。表皮细胞更新速率的增加通常是由表皮基底细胞更快的再生速率造成的,其可以由不同的刺激造成,如化学或物理伤害、不利的环境条件或基底细胞分裂的直接刺激物。
化学伤害的一些例子包括过敏的或非过敏的接触刺激、pH极值或角质层与家用的或工业的化学品或污染物的相互作用。物理伤害可以包括皮肤磨耗、摩擦(即在脚底或脚后跟)或通过物理剥离(即美容面膜(cosmeticmasks)或通过胶带剥离(tape stripping)除去角质层。直接或间接刺激基底细胞分裂的试剂包括类维生素A和屏障破坏药物(barrier disrupters)。例如,美国专利号5,720,963公开了一种由羟基酸、类维生素A和脑苷脂类组合造成角质层的慢性损伤,并导致结构性破坏的皮肤的表皮和真皮的修复。例如,美国专利号6,495,126利用洗涤剂和螯合剂的组合刺激导致角化细胞变松的内源的角质层胰蛋白酶,导致增加的表皮取代速率和慢性防老的益处。能够造成更块的表皮更新率的不利环境曝露包括来自太阳的UVA、UVB和IR射线和伴随低相对湿度的寒冷(即低的露点)。
几个上述方法已经表明具有不同的缺陷,如显著的皮肤刺激或皮肤毒性。而且,这些方法的大多数涉及利用启动修复机制的皮肤慢性损害。对大多数已有的治疗,会需要一段时间,达几周或几个月,在此期间,皮肤受到刺激,此期间之后,耐受性建立和刺激症状会减轻和/或停止。
发明内容
本发明通过提供可用于皮肤治疗应用的组合物,克服本技术领域的不足。本发明的组合物可以包括卡卡杜李提取物和/或巴西莓提取物。而且,如图和实施例(通过引用包括在该部分)所示,发明者已经发现,卡卡杜李提取物和巴西莓提取物的组合产生对皮肤有益的协同和互补效应。
在某些实施方式中,组合物被制成局部护肤组合物。所述组合物可以是化妆品组合物。在其他方面,所述组合物可以被包含在化妆品载体中。化妆品载体的非限定性的例子在本说明书的其它部分被公开,并且为本技术领域的技术人员所知。化妆品载体的例子包括乳剂(例如,油包水和水包油)、膏、洗液、溶液(例如,水溶液或水醇(hydro-alcoholic)溶液)、无水碱(例如,唇膏或粉末)、凝胶和软膏。在其它的非限定性的实施方式中,本发明的组合物可以被包含在防老的、清洁的或润湿的产品中。所述组合物也可以被配制用于局部皮肤涂敷,在使用期间每天至少涂敷1、2、3、4、5、6、7或更多次数。在本发明的其它方面,所述组合物能够贮存稳定或颜色稳定或两者都稳定。也可以期望,选择组合物的粘度能获得期望的结果(例如,根据期望的组合物类型,这样的组合物的粘度可以为大约1cps到1百万cps以上或从中可导出的任何范围或整数(例如,2cps、3、4、5、6、7、8、9、10、20、30、40、50、60、70、80、90、100、200、300、400、500、600、700、800、900、1000、2000、3000、4000、5000、6000、7000、8000、9000、10000、20000、30000、40000、50000、60000、70000、80000、90000、100000、200000、300000、400000、500000、600000、700000、800000、900000、1000000cps等)。
本发明的组合物可以包括重量百分比为大约0.001%到大约50%的卡卡杜李提取物和/或巴西莓提取物。然而,应该认识到,基于所期望的结果,组合物中的卡卡杜李提取物和/或巴西莓提取物的量可以在该范围以下、以内或以上被改性。因此,卡卡杜李提取物和/或巴西莓提取物的量可以包括小于0.001%。在其它方面,所述组合物可以包括0.002、0.003、0.004…1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、25、30、35、40、45、50、60、70、80、90、95、96、97、98、99%或以上或从此处可导出的任何范围的重量百分比或体积百分比的卡卡杜李提取物和/或巴西莓提取物。
本发明的组合物也可以被改性,以具有期望的氧自由基吸收能力(ORAC)值。在某些非限定性方面,本发明的组合物,卡卡杜李提取物和/或巴西莓提取物可以被改性,以具有每mg至少大约为以下数值的ORAC值:1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、35、40、45、50、55、60、70、80、90、95、100、200、300、400、500、600、700、800、900、1000、2000、3000、4000、5000、6000、7000、8000、9000、10000、15000、20000、30000、50000、100000或以上或从此处可导出的任何范围。
在本发明的其它非限定性的发面,所述组合物可以进一步包括维生素、矿物质、必需脂肪酸、氨基酸、类黄酮和/或蛋白或它们的结合。维生素的非限定性的例子包括维生素B类(例如,B1、B2、B6、B12、烟酸、叶酸、生物素和泛酸)、维生素C、维生素D、维生素E(例如,生育酚或醋酸生育酚)、维生素A(例如,棕榈酸酯、棕榈酸视黄酯或视黄酸)和维生素K。矿物质的非限定性的例子包括铁、钾、磷、镁、锰、硒和钙。必需脂肪酸的非限定性例子包括Omega3(亚麻酸)、Omega6(亚油酸)和Omega9(油酸)必需脂肪酸或它们的组合。氨基酸的非限定性例子包括必需氨基酸(例如,赖氨酸、亮氨酸、异亮氨酸、蛋氨酸、苯丙氨酸、苏氨酸、色氨酸、缬氨酸、组氨酸或精氨酸)和非必需氨基酸(例如,丝氨酸、天冬酰胺、谷氨酰胺、天冬氨酸、谷氨酸、丙氨酸、酪氨酸、半胱氨酸、甘氨酸或脯氨酸)。类黄酮的非限定性例子包括花青苷化合物(例如,花青素-3-葡萄糖苷和花青素-3-芸香糖苷)。
在非限定性方面的组合物可以具有约6到约9的pH。在其它方面,所述pH可以是1、2、3、4、5、6、7、8、9、10、11、12、13或14。所述组合物可以包括甘油三酯。非限定性例子包括小、中和大链的甘油三酯。在某些方面,所述甘油三酯是中链甘油三酯(例如,辛酸癸酸甘油三酯)。所述组合物也可以包括防腐剂。防腐剂的非限定性例子包括对羟基苯甲酸甲酯、对羟基苯甲酸丙酯或一种含有对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的混合物。
所述组合物也可以包括精油。精油的非限定性例子是在说明书中所述的精油和本技术领域普通技术人员所知的精油。例子包括芝麻油、澳洲坚果油(macadamia nut oil)、茶树油、月见草油(evening primrose oil)、西班牙鼠尾草油(Spanish sage oil)、西班牙迷迭香油(Spanish rosemary oil)、芫荽油(Coriander oil)、百里香油(Thyme oil)或众香子油(Pimento berries oil)。在某些方面,所述组合物不包括非挥发油。所述组合物可以包括增稠剂和/或洗涤剂。
也公开了治疗或预防皮肤疾病的方法,其包括局部涂敷一种包含高ORAC值、卡卡杜李提取物和/或巴西莓提取物的组合物,其中组合物的局部涂敷可治疗皮肤病。皮肤病的非限定性例子包括搔痒、蜘蛛状血管病(spider veins)、着色斑(lentigo)、老人斑(age spots)、老年性紫癜(senilepurpura)、角化病(keratosis)、黑斑病(melasma)、疙瘩(blotches)、细线或皱纹、小结、日光灼伤皮肤(sun damaged skin)、皮炎(包括但不限于脂溢性皮炎、钱币形皮炎(nummular dermatitis)、接触性皮炎、特应性皮炎(atopicdermatitis)、剥脱性皮炎、口周皮炎和停滞性皮炎)、牛皮癣(psoriasis)、毛囊炎(folliculitis)、酒渣鼻(rosacea)、座疮、脓疱病、丹毒、红癣、湿疹和其它的炎性皮肤病。在某些非限定性方面,皮肤病可以通过曝露于紫外线、老化、刺激、慢性太阳照射、环境污染物、空气污染、风、冷、热、化学品、疾病病理、吸烟、营养缺乏所导致。皮肤可以是面部皮肤或非面部皮肤(例如,胳膊、腿、手、胸、背、脚等)。所述方法可进一步包括识别需要皮肤治疗的人。所述人可以是男性或女性。所述人的年龄可以为至少1、2、3、4、5、6、7、8、9、10、15、20、25、30、35、40、45、50、55、60、65、70、75、80、85、90、95或更大的年龄或可从此处导出的任何范围。所述方法也可以包括涂敷有效量以获得以下作用:增加皮肤角质层的更新率;增加成纤维细胞胶原的合成;增加细胞的抗氧化防御机制(例如,抗氧化剂的外源性添加能够支持、补充或阻止皮肤细胞(例如,角质细胞、黑素细胞、朗格罕氏细胞(langerhans cell)等)内的细胞抗氧化剂的损失,如会减少或阻止皮肤损伤的过氧化氢酶和谷胱甘肽,细胞的蛋白和脂质的损耗);抑制黑素细胞中的黑色素的产生;降低或阻止皮肤的氧化性损伤(包括减少皮肤中脂质过氧化物的量和/或蛋白的氧化)。
在某些实施方式中,所述组合物能够减少细胞内的内氧化和/或外氧化性损伤。在另一个方面,所述组合物能够增加细胞内的胶原合成。所述组合物,如通过减少细胞内炎症细胞因子的产生也能够减少皮肤炎症。这样的细胞的非限定性例子包括人类表皮角质细胞、人类真皮成纤维细胞、人类黑素细胞、衍生自三维人类细胞的离体组织等同物包括人类角质细胞、人类成纤维细胞或人类黑素细胞或它们的任意组合(例如,人类角质细胞和人类成纤维细胞的组合或人类角质细胞和人类黑素细胞的组合)。
也公开了使皮肤发亮或均匀皮肤色调的方法,其包括将本发明的组合物涂敷到皮肤上。所述方法可以进一步包括识别需要发亮皮肤或均匀皮肤色调的人。所述方法可以进一步包括抑制皮肤细胞中的黑素生成、抑制皮肤细胞中酪氨酸酶或酪氨酸酶的合成,或抑制皮肤细胞中将黑色素运输到角质细胞。所述组合物能够作为α黑色素刺激性激素的拮抗剂发挥作用。所述组合物能够均匀皮肤的着色。在非限定性方面,发亮皮肤可以包括减少老人斑、皮肤变色或雀斑的出现。
包括将本发明的组合物涂敷到皮肤上治疗色素沉着过度的方法也被公开。所述方法也可以包括识别需要治疗色素沉着过度的人。发明人预期的附加方法包括减少老人斑、皮肤变色或雀斑的出现的方法,减少或预防皮肤的细线或皱纹的出现或增加皮肤结实的方法。
包含卡卡杜李提取物和巴西莓提取物的组合物能够产生协同效应。例如,所述两种提取物能够一起协同作用,其产生的作用超过所述提取物在单独的组合物中使用时所期望的作用。非限定性的协同作用包括内或外氧化性损伤的减少、增加胶原的产生、炎症应答的减少和黑素生成的抑制。
包括卡卡杜李提取物和巴西莓提取物的组合物也可以互补的方式进行作用。例如,卡卡杜李提取物通过不减少某些细胞因子,能够减少炎症应答(例如,减少炎症细胞因子的产生),或通过巴西莓提取物不显著减少某些细胞因子减少炎症应答,反之亦然。
包括本发明的组合物的试剂盒也是可预期的。在一些实施方式中,所述组合物被包括在容器中。所述容器可以是瓶子、分配器或包装。所述容器可以分配预定量的所述组合物。在某些方面,所述组合物以喷雾剂、块或液体分配。所述容器在其表面上可以包括标记。所述标记可以是文字、缩写、图或符号。
包括本发明的组合物的产品也是可预期的。在非限定性方面,所述产品可以是化妆品。所述化妆品可以是本说明书的其它部分所述的那些或本技术领域技术人员所知的那些。产品的非限定性的例子包括保湿剂、膏、洗液、皮肤软化剂、粉底、晚霜、唇膏、清洁剂、调色剂、防晒剂、面膜或防老产品。
可以预期,通过本发明的任何方法或组合物,本说明书所述的任何实施方式可以被实现,反之亦然。而且,本发明的组合物可以被用于实现本发明的方法。
“非挥发性油”包括在常温或室温下不蒸发的那些物质。
术语“混合物”、“混合”和“混合的”或这些术语的任何变体,当用在所述权利要求书和/或说明书中时,包括搅动、掺和、分散、碾磨、均化和其它相似的方法。混合所公开的组分或成分可以形成溶液。在其它的实施方式中,所述混合物可以不形成溶液。所述成分/组分也可以作为不溶解的胶态悬浮液存在。
术语“大约”或“近似”被定义为与本技术领域的技术人员所理解的接近,并且在一个非限定性的实施方式中,所述术语被定义为在10%内,优选地在5%内,更优选地在1%内,最优选地在0.5%内。
术语“抑制”或“减少”或这些术语的任何变体,当用于权利要求书和/或说明书中时,包括可测量的减少或完全的抑制已获得期望的结果。
术语“有效的”,当该术语被用于说明书和/或权利要求书时,指足以获得期望的、预期的或打算的结果。
单词“a”或“an”当与术语“包括”结合用于权利要求书和/或说明书时,可以指“一个”,但是它们也与意思“一个或以上”、“至少一个”和“一个或大于一个”一致。
术语“或”在权利要求书中的使用被用来指“和/或”,除非清楚地指明唯一的替代物,或所述替代物是互斥的,但是所述公开内容支持指唯一的替代物和“和/或”的定义。
如在本说明书和权利要求(一项或多项)中所用,单词“包含(comprising)”(和包括的任何形式,如“comprise”和“comprises”)、“具有(having)”(和具有的任何形式,如“have”和“has”)、“包括(including)”(和包括的任何形式,如“includes”和“includes”)或“含有(containing)”(和含有的任何形式,如“contains”和“contain”)是包含的或开放式的,并且不排除附加的、未叙述的元素或方法步骤。
本发明的其它的目标、特征和优点将从以下具体的描述中变得显而易见。然而,应理解,所述具体的描述和实施例,尽管指出了发明的具体实施方式,仅仅通过说明性的方式给出。另外,可以预期的是,在本发明的精神和范围内,该具体描述的变化或改变对本技术领域的技术人员是显而易见的。
附图说明
以下附图构成本发明的说明书部分,并且被包括以进一步说明本发明的某些方面。通过参照一个或多个这些附图结合下面所述的具体实施方式的详细描述,本发明可以被更好地理解。
图1.卡卡杜李提取物对人类表皮角质细胞的抗氧化作用。E代表根据分析所述的外源抗氧化剂(外源的意思是能够减少氧化,其是外来引入的)。1%是在每体积的水中被稀释的卡卡杜李的体积。初始的液体提取物相对在10-20%的变性酒精和>50%的1,3丁二醇中的重量百分比为20-30%。通过水稀释制备的10%的该提取物的贮备液(2-3%的果汁提取物),其进一步在分析中被稀释到1.0%和0.1%(0.2-0.3%和0.02-0.03%的卡卡杜李果汁提取物,基于初始的提取物的量)。
图2.通过曝露于卡卡杜李提取物,影响真皮细胞中胶原的产生。与图1相似,初始的液体提取物相对在10-20%的变性酒精和>50%的1,3丁二醇中的重量百分比为20-30%。通过水稀释制备10%的该提取物的贮备液(2-3%的果汁提取物),其进一步在分析中被稀释到1.0%和0.1%(0.2-0.3%和0.02-0.03%的卡卡杜李果汁提取物,基于初始的提取物的量)。
图3.关于曝露于卡卡杜李提取物的人类表皮角质细胞的炎症曲线。
图4.巴西莓提取物对人类表皮角质细胞的抗氧化作用。E代表根据分析所述的外源抗氧化剂(外源的意思是能够减少氧化,其是外来引入的)。I代表内源的,其涉及减少内部氧化的能力,是细胞内代谢的结果。初始的粉末提取物相对在70-80%载体蛋白中的重量百分比为20-30%。所述初始干粉提取物相对在以50:50的比例含有水和90%的变性酒精的混合物中的重量对体积的比例(w/v)为100mg/ml,以产生100×贮备液。为了进行分析,得到的100×贮备液通过水稀释到1.0%和0.1%(1.0mg/ml和0.1mg/ml)进行制备。
图5.通过曝露于巴西莓提取物,影响真皮细胞中胶原的产生。初始的粉末提取物相对在70-80%载体蛋白中的重量百分比为20-30%。所述初始干粉提取物相对在以50:50的比例含有水和90%的变性酒精的混合物中的重量对体积的比例为100mg/ml,以产生100×贮备液。为了进行分析,得到的100×贮备液通过水稀释到1.0%和0.1%(1.0mg/ml和0.1mg/ml)进行制备。
图6.关于曝露于巴西莓提取物的人类表皮角质细胞的炎症曲线。
图7.卡卡杜李提取物和巴西莓提取物的互补炎症应答曲线。
具体实施方式
在今天的形象意识社会,人们一直在寻找能够改善他们皮肤视觉外观的产品。通常,老化皮肤、不均匀的皮肤色调或由如紫外线、慢性阳光照射、环境污染物、化学药品、疾病病理或吸烟等环境因素造成的皮肤损害与不美的皮肤相关。在以前的改善皮肤视觉外观的尝试中已经被表明具有不同的缺陷,如皮肤刺激和长的痊愈时间。
本发明是取代目前用于治疗老化皮肤、环境性皮肤的伤害、不均匀的皮肤色调和其它皮肤疾病的类维生素A化合物或其它的组合物和成分的一种有效取代物。在一个非限定性方面,通过提供含有卡卡杜李提取物和/或巴西莓提取物的组合物,本发明可以用于改善皮肤的外观、生理功能、临床性质或生物物理性质。本发明的这些和其它方面在下面被进一步地具体说明。
A.卡卡杜李提取物
卡卡杜李(Terminalia ferdinandiana),也称为雄山羊李(Billygoat plum)、Gubinge或Murunga,是来自使君子科(Combretacae)的有花植物。卡卡杜李能够在澳大利亚西北部到阿纳姆地(eastern Arnhem Land)东部的热带林地发现。该果实具有高的维生素C浓度,含有每100g果实达4000mg的维生素C。卡卡杜李也具有高的ORAC值。卡卡杜李也包括植物化学物,如没食子酸(gallic acid)、鞣花酸(ellagic acid)和相关的化合物。这些植物化学物具有已涉及抑制癌的抗氧化物性质。没食子酸具有抗菌、抗病毒和抗真菌活性,并且也显示抗炎、抗肿瘤、抗诱变和抗支气管扩张的活性。鞣花酸具有针对许多人类组织中的广范围的致癌物的抗癌作用。
卡卡杜李提取物可商业获得,并且也可以被本技术领域的普通技术人员用标准的分离技术分离。例如,卡卡杜李可以用机械手段破坏,产生果浆(puree)。所述果浆接着被加工到基本上不含有杂质或不期望的固体例如茎干。所述果浆接着可以被注入浅的容器并迅速地曝露于低温,例如在-20℃或更低,即速冻(flash frozen),优选地在真空下,以除去含水量(冻干)。获得的李提取物接着可以被用于本发明的组合物中。可选地,美国公开号2005/0163880,其通过引用被包括,描述了制备卡卡杜李粉末的附加的非限定性方法。总之,所述方法包括:碎裂卡卡杜李果实;用酶处理碎裂的卡卡杜李材料以至少部分消化材料;榨汁卡卡杜李材料和干燥汁液产生粉末。
在其它的非限定性方面,所述卡卡杜李提取物可以进一步被加入具有对皮肤有益性质的成分。这些成分的非限定性例子包括在整个本说明书中列出的那些,包括,例如,抗氧化剂、维生素、矿物质和氨基酸。在一些方面,对所述卡卡杜李加料可以增加卡卡杜李提取物和/或本发明的组合物的ORAC值。
B.巴西莓提取物
巴西莓可以从生长在巴西亚马逊雨林中的棕榈树(Euterpe oleracea)类中获得。其果实天生是3到8个的串。巴西莓含有维生素、矿物质和必需脂肪酸、该列包括维生素B1、B2和B3、维生素C、维生素E、铁、钾、磷、钙、必需脂肪酸Omega6和Omega9、所有必需的氨基酸、类黄酮和蛋白。在巴西莓中发现的类黄酮包括花青苷如原花色素、花青素-3-葡萄糖苷和花青素-3-芸香糖苷。巴西莓中多酚的含量也高。已经报道,巴西莓具有达33倍的红酒葡萄的抗氧化剂含量并且在任何莓类中具有最高的ORAC值。
巴西莓提取物可从许多公司商业获得,包括,例如,Global Laboratoriesand NHS Labs Inc.,Eagle,Idaho。另外,本技术领域的普通技术人员将能够用本技术领域已知的任何合适的方法从完整的巴西莓分离巴西莓提取物。在一个非限定性例子中,巴西莓可以用机械手段破坏,产生果浆。所述果浆接着被加工到基本上不含有杂质或不期望的固体例如茎干。所述果浆接着可以被注入浅的容器并迅速地曝露于低温,例如在-20℃或更低,即速冻,优选地在真空下,以除去含水量(冻干)。获得的莓提取物接着可以被用于本发明的组合物中。
在其它的非限定性方面,所述巴西莓提取物可以进一步被加入具有对皮肤有益性质的成分。这些成分的非限定性的例子包括在整个本说明书中列出的那些,包括,例如,抗氧化剂、维生素、矿物质和氨基酸。在一些方面,使富含所述巴西莓可以增加巴西莓提取物和/或本发明的组合物的ORAC值。
C.氧自由基吸收能力
氧自由基吸收(或吸收率)能力(ORAC)是测量成分的或组合物的抗氧化剂活性的分析。本质上,该分析能够定量其抑制已知的导致细胞的损害(例如,皮肤细胞)的氧化剂,如氧自由基的作用的度和所需的时间长。本发明的卡卡杜李提取物、巴西莓提取物和组合物的ORAC值可以通过本技术领域普通技术人员所知的方法确定(见,美国公开号2004/0109905和2005/0163880;Cao等(1993)),所有这些方法通过引用被包括。总之,Cao等(1993)所述的分析测量了实验材料中的抗氧化剂化合物抑制B-藻红蛋白(B-phycoerythrin)(B-PE)荧光下降的能力,B-藻红蛋白荧光下降由过氧化氢自由基生成剂AAPH诱导。
D.本发明的组合物
普通技术人员将会意识到本发明的组合物包括成分的任何数目的组合(例如,卡卡杜李提取物、巴西莓提取物、遮光剂(sun blocking agent)、急性或慢性保湿剂(包括,例如,湿润剂、闭塞剂(occlusive agent)和影响皮肤天然保湿机制的药物)、抗氧化剂、具有阻止UVA和/或UVB的防晒剂、软化剂、抗刺激剂、维生素、微量金属、抗菌剂、植物提取物、香料、染料和色料成分(color ingredients)、结构剂(structuring agent)、乳化剂等)。尽管具体成分的一些浓度范围在本说明书的其它部分已经说明,但是也可以预期,在一些实施方式中,这些和其它成分的浓度可以在那些具体的范围之外变化。例如,在一个非限定性方面,本发明的组合物可以包括至少大约0.0001%、0.0002%、0.0003%、0.0004%、0.0005%、0.0006%、0.0007%、0.0008%、0.0009%、0.0010%、0.0011%、0.0012%、0.0013%、0.0014%、0.0015%、0.0016%、0.0017%、0.0018%、0.0019%、0.0020%、0.0021%、0.0022%、0.0023%、0.0024%、0.0025%、0.0026%、0.0027%、0.0028%、0.0029%、0.0030%、0.0031%、0.0032%、0.0033%、0.0034%、0.0035%、0.0036%、0.0037%、0.0038%、0.0039%、0.0040%、0.0041%、0.0042%、0.0043%、0.0044%、0.0045%、0.0046%、0.0047%、0.0048%、0.0049%、0.0050%、0.0051%、0.0052%、0.0053%、0.0054%、0.0055%、0.0056%、0.0057%、0.0058%、0.0059%、0.0060%、0.0061%、0.0062%、0.0063%、0.0064%、0.0065%、0.0066%、0.0067%、0.0068%、0.0069%、0.0070%、0.0071%、0.0072%、0.0073%、0.0074%、0.0075%、0.0076%、0.0077%、0.0078%、0.0079%、0.0080%、0.0081%、0.0082%、0.0083%、0.0084%、0.0085%、0.0086%、0.0087%、0.0088%、0.0089%、0.0090%、0.0091%、0.0092%、0.0093%、0.0094%、0.0095%、0.0096%、0.0097%、0.0098%、0.0099%、0.0100%、0.0200%、0.0250%、0.0275%、0.0300%、0.0325%、0.0350%、0.0375%、0.0400%、0.0425%、0.0450%、0.0475%、0.0500%、0.0525%、0.0550%、0.0575%、0.0600%、0.0625%、0.0650%、0.0675%、0.0700%、0.0725%、0.0750%、0.0775%、0.0800%、0.0825%、0.0850%、0.0875%、0.0900%、0.0925%、0.0950%、0.0975%、0.1000%、0.1250%、0.1500%、0.1750%、0.2000%、0.2250%、0.2500%、0.2750%、0.3000%、0.3250%、0.3500%、0.3750%、0.4000%、0.4250%、0.4500%、0.4750%、0.5000%、0.5250%、0.0550%、0.5750%、0.6000%、0.6250%、0.6500%、0.6750%、0.7000%、0.7250%、0.7500%、0.7750%、0.8000%、0.8250%、0.8500%、0.8750%、0.9000%、0.9250%、0.9500%、0.9750%、1.0%、1.1%、1.2%、1.3%、1.4%、1.5%、1.6%、1.7%、1.8%、1.9%、2.0%、2.1%、2.2%、2.3%、2.4%、2.5%、2.6%、2.7%、2.8%、2.9%、3.0%、3.1%、3.2%、3.3%、3.4%、3.5%、3.6%、3.7%、3.8%、3.9%、4.0%、4.1%、4.2%、4.3%、4.4%、4.5%、4.6%、4.7%、4.8%、4.9%、5.0%、5.1%、5.2%、5.3%、5.4%、5.5%、5.6%、5.7%、5.8%、5.9%、6.0%、6.1%、6.2%、6.3%、6.4%、6.5%、6.6%、6.7%、6.8%、6.9%、7.0%、7.1%、7.2%、7.3%、7.4%、7.5%、7.6%、7.7%、7.8%、7.9%、8.0%、8.1%、8.2%、8.3%、8.4%、8.5%、8.6%、8.7%、8.8%、8.9%、9.0%、9.1%、9.2%、9.3%、9.4%、9.5%、9.6%、9.7%、9.8%、9.9%、10%、11%、12%、13%、14%、15%、16%、17%、18%、19%、20%、21%、22%、23%、24%、25%、26%、27%、28%、29%、30%、35%、40%、45%、50%、60%、65%、70%、75%、80%、85%、90%、95%或99%或从此处可导出的任何范围的成分,或在整个说明书和权利要求书被提及的至少一种成分。在非限定性方面,所述百分数可以按总组合物的重量或体积计算。本技术领域普通技术人员将会理解,所述浓度可以根据给定组合物中的成分的加入、取代和/或减少变化。
本发明的公开的组合物也可以包括各种抗氧化剂以阻滞一种或多种组分的氧化。另外,通过防腐剂如各种抗菌剂和抗真菌剂,包括但不限于对羟基苯甲酸酯(例如,对羟基苯甲酸甲酯、对羟基苯甲酸丙酯)、氯丁醇、苯酚、山梨酸、硫柳汞或它们的组合,可以实现阻止微生物的作用。
E.载体
本发明的组合物可以被掺入到所有类型的载体中。合适的载体的非限定性例子包括乳剂(例如,水包油、水包油包水(water-in-oil-in-water)、油包水、油包水包油(oil-in-water-in-oil)、油包水包聚硅氧(oil-in-water-in-silicone)乳剂)、膏、洗液、溶液(水溶液和水-醇溶液)、无水碱(例如,唇膏或粉末)、凝胶和软膏或通过其它方法或被本技术领域普通技术人员将所知的前述的任意组合(Remington,1990)。变体和其它合适的载体对本技术领域普通技术人员是显而易见的,并且适合用于本发明。在本发明的一些方面,以这样的方式选择的所述化合物、成分和试剂的浓度和组合是重要的,该组合是化学相容的,并且不形成复合物,从获得产物中沉淀。
也可以预期,整个本说明书所确定的成分,包括但不限于卡卡杜李提取物和/或巴西莓提取物,其可以用胶囊包起来以输送到靶区域如皮肤。胶囊技术的非限定性例子包括使用脂质体、囊泡和/或纳米颗粒(例如,包含有聚合材料的可生物降解的和非生物降解的胶体颗粒,在该胶体颗粒中,所述成分被截留、封闭和/吸收-例子包括纳米球和纳米胶囊),它们可以被用作输送载体将所述成分输送到皮肤(见,例如美国专利号6,387,398;美国专利号6,203,802;美国专利号5,411,744;Kreuter1998)。
F.化妆品和制品
本发明的组合物也可以被用于许多化妆品,包括但不限于,防晒产品、免晒皮肤美黑产品(sunless skin tanning products)、发用产品(hair products)、指甲用产品、保湿膏、益肤霜(skin benefit creams)和洗液、软化剂、白天用洗液(day lotions)、凝胶、软膏、粉底、晚霜、唇膏、清洁剂、调色剂、面膜或其它已知的化妆品或应用。另外,所述化妆品可以被制成驻留(leave-on)或冲洗产品。在一些方面,本发明的组合物是独立的产品。
G.可以与本组合物组合使用的附加化合物、药剂和成分
本发明的组合物可以包括其它有益的试剂和化合物,例如防晒剂、急性或慢性保湿剂(包括,例如湿润剂、闭塞剂和影响皮肤天然保湿机制的药剂)、抗氧化剂、具有阻止UVA和/或UVB的防晒剂、软化剂、抗刺激剂、维生素、微量金属、抗菌剂、植物提取物、香料、染料和色料成分、结构剂和/或乳化剂等(见美国专利号6,290,938)。
1.防晒剂
可以与本发明的组合物组合使用的防晒剂包括化学的和物理的防晒剂。可以使用的化学防晒剂的非限定性的例子包括对氨基苯甲酸(PABA)、PABA酯(对氨基苯甲酸甘油酯、对二甲基氨基苯甲酸戊酯(amyldimethylPABA)和对二甲基氨基苯甲酸辛酯(octyldimethyl PABA)、对氨基苯甲酸丁酯、对氨基苯甲酸乙酯、对二羟基丙基氨基苯甲酸乙酯(ethyldihydroxypropyl PABA)、苯酮(羟苯甲酮(oxybenzone)、磺异苯酮(sulisobenzone)、二苯甲酮(benzophenone)和二苯甲酮-1到12)、肉桂酸酯(和甲氧肉桂酸辛酯、对-甲氧肉桂酸异戊酯、甲氧肉桂酸辛酯、对甲氧肉桂酸乙氧乙酯(cinoxate)、二异丙基肉桂酸甲酯(diisopropyl methyl cinnamate)、甲氧肉桂酸DEA盐(DEA-methoxycinnamate)、二异丙基肉桂酸乙酯(ethyldiisopropylcinnamate)、甘油二甲氧肉桂酸辛酸酯(glyceryl octanoatedimethoxycinnamate)和甲氧肉桂酸乙酯(ethyl methoxycinnamate))、肉桂酸酯类、水杨酸酯类(原膜散酯(homomethyl salicylate)、水杨酸苄酯、水杨酸乙二醇酯(glycol salicylate)、水杨酸异丙苄酯(isopropylbenzyl salicylate))、邻氨基苯甲酸酯、尿刊酸乙酯(ethyl urocanate)、水杨酸三甲环己酯(homosalate)和Parsol1789。物理防晒剂的非限定性例子包括高岭土、滑石粉、凡士林和金属氧化物(例如,二氧化钛和氧化锌)。
2.保湿剂
可以与本发明的组合物一并使用的保湿剂的非限定性例子包括氨基酸、硫酸软骨素、双甘油、赤藓醇、果糖、葡萄糖、甘油、甘油聚合物、乙二醇、1,2,6-己三醇、蜂蜜、透明质酸、氢化蜂蜜、氢化淀粉水解物、肌醇、乳糖醇、麦芽糖醇、麦芽糖、甘露醇、天然的保湿因子、PEG-15丁二醇、聚甘油山梨醇、吡咯烷酮羧酸盐、PCA钾、丙二醇、葡萄糖醛酸钠、PCA钠、山梨醇、蔗糖、海藻糖、尿素和木糖醇。
其它的例子包括乙酰化羊毛脂、乙酰羊毛脂醇、丙氨酸、藻提取物、库拉索芦荟(aloe barbadensis)、库拉索芦荟提取物、库拉索芦荟凝胶、药用蜀葵提取物、杏(prunus armeniaca)仁油、精氨酸、精氨酸天冬氨酸、山金车提取物、天冬氨酸、鳄梨(persea gratissima)油、防渗鞘脂、丁醇、蜂蜡、二十二醇、β-谷甾醇、桦树(betula alba)皮提取物、琉璃苣(borago officinalis)提取物、山金车花(ruscus aculeatus)提取物、丁二醇、金盏菊提取物、金盏菊油、小烛树(euphorbia cerifera)蜡、菜籽油、辛酸/癸酸甘油三酯、小豆蔻(elettaria cardamomum)油、巴西棕榈(copernicia cerifera)蜡、胡萝卜(daucuscarota sativa)油、蓖麻(ricinus communis)油、神经酰胺、地蜡、鲸蜡硬脂醇聚醚-5、鲸蜡硬脂醇聚醚-12、鲸蜡硬脂醇聚醚-20、辛酸十六十八醇酯(cetearyl octanoate)、鲸蜡醇醚-20、鲸蜡醇醚-24、十六烷基乙酸酯(cetylacetate)、十六烷基辛酸酯(cetyl octanoate)、十六烷基棕榈酸酯(cetylpalmitate)、春黄菊(anthemis nobilis)油、胆固醇、胆固醇酯、羟基硬脂酸胆固醇酯、柠檬酸、香紫苏(salvia sclarea)油、可可(theobroma cacao)油、椰油醇辛酸酯/癸酸酯(coco-caprylate/caprate)、椰子(cocos nucifera)油、胶原、胶原氨基酸、玉米油、脂肪酸、油酸癸酯、聚二甲基硅氧烷共聚醇(dimethicone copolyol)、聚二甲基硅氧烷醇、己二酸二辛酯、琥珀酸二辛酯、二聚季戊四醇六辛酸酯/六癸酸酯(dipentaerythritylhexacaprylate/hexacaprate)、DNA、赤藓醇、乙氧基二甘醇(ethoxydiglycol)、亚油酸乙酯、蓝桉油(eucalyptus globulus oil)、月见草(oenothera biennis)油、脂肪酸、老鹤草(geranium maculatum)油、葡糖胺、葡萄糖谷氨酸酯、谷氨酸、甘油聚醚-26、甘油(glycerin)、甘油(glycerol)、甘油二硬脂酸酯、甘油羟基硬脂酸酯、甘油月桂酸酯、甘油亚油酸酯、甘油肉豆蔻酸酯、甘油油酸酯、甘油硬脂酸酯、甘油硬脂酸酯SE、甘氨酸、乙二醇硬脂酸酯、乙二醇硬脂酸酯SE、葡萄糖胺聚糖、葡萄(vitis vinifera)籽油、榛(美洲榛(corylusamericana))果油、榛(欧洲榛(corylus avellana))果油、己二醇、透明质酸、杂交红花子(carthamus tinctorius)油、氢化蓖麻油、氢化可可甘油酯类、氢化椰子油、氢化羊毛脂、氢化卵磷脂、氢化棕榈油甘油酯类、氢化棕榈仁油、氢化大豆油、氢化牛脂酸甘油酯、氢化植物油、水解胶原、水解弹性蛋白、水解葡糖氨基聚糖、水解角蛋白、水解大豆蛋白、羟基化羊毛脂、羟基脯氨酸、异十六烷基硬脂酸酯、异十六烷基硬脂酰硬脂酸酯、油酸异癸酯、异硬脂酸异丙酯、羊毛脂酸异丙酯、豆蔻酸异丙酯、棕榈酸异丙酯、硬脂酸异丙酯、异硬脂酰胺DEA、异硬脂酸、异硬脂酰乳酸酯、异硬脂酰新戊酸酯、素方花(jasminum officinale)油、荷荷巴(buxus chinensis)油、海草油、石栗(aleurites moluccana)果油、乳酰胺MEA、羊毛脂醇醚(laneth)-16,羊毛脂醇醚-10乙酸酯、羊毛脂、羊毛脂酸、羊毛脂醇、羊毛脂油、羊毛脂蜡、薰衣草(lavandula angustifolia)油、卵磷脂、柠檬(citrus medica limonum)油、亚油酸、亚麻酸、澳大利亚坚果油、麦芽糖醇、母菊(chamomilla recutita)油、甲基葡萄糖苷倍半硬脂酸酯、甲基硅烷醇PCA、矿物油、貂油、被孢霉油、乳酸肉豆蔻酯、肉豆蔻酸肉豆蔻酯、丙酸肉豆蔻酯、新戊二醇二辛酸酯/二癸酸酯、辛基十二烷醇、肉豆蔻酸辛基十二酯、肉豆蔻酰肉豆蔻酸辛基十二酯、羟基硬脂酸辛酯、棕榈酸辛酯、水杨酸辛酯、硬脂酸辛酯、油酸、橄榄(olea europaea)油、甜橙(citrus aurantium dulcis)油、棕榈(elaeisguineensis)油、棕榈酸、泛酰巯基乙胺、泛醇、泛醇基乙基醚、石蜡、PCA、桃(prunus persica)仁油、花生(arachis hypogaea)油、PEG-8C12-18酯、PEG-15椰油胺、PEG-150双硬脂酸酯、PEG-60异硬脂酸甘油酯、PEG-5硬脂酸甘油酯、PEG-30硬脂酸甘油酯、PEG-7氢化蓖麻油、PEG-40氢化氢化蓖麻油、PEG-60氢化蓖麻油、PEG-20甲基葡萄糖苷倍半硬脂酸酯、PEG40失水山梨醇全油酸酯、PEG-5大豆甾醇、PEG-10大豆甾醇、PEG-2硬脂酸酯、PEG-8硬脂酸酯、PEG-20硬脂酸酯、PEG-32硬脂酸酯、PEG40硬脂酸酯、PEG-50硬脂酸酯、PEG-100硬脂酸酯、PEG-150硬脂酸酯、十五内酯、薄荷(mentha piperita)油、凡士林、磷脂、多氨基酸多糖缩合物、聚甘油-3二异硬脂酸酯、聚季铵盐-24、聚山梨脂20、聚山梨脂40、聚山梨脂60、聚山梨脂80、聚山梨脂85、肉豆蔻酸钾、棕榈酸钾、丙二醇、丙二醇二辛酸酯/二癸酸酯、二辛酸丙二醇酯、二壬酸丙二醇酯、月桂酸丙二醇酯、硬脂酸丙二醇酯、硬脂酸丙二醇酯SE、PVP、二棕榈酸吡哆醇酯、视黄醇、棕榈酸视黄酯、米(oryza sativa)糠油、RNA、迷迭香(rosmarinus officinalis)油、玫瑰油、红花(carthamus tinctorius)油、鼠尾草(salvia officinalis)油、檀香(santalum album)油、丝氨酸、血清蛋白、芝麻(sesamum indicum)油、牛油果脂(butyrospermum parkii)、丝粉、硫酸软骨素钠、透明质酸钠、乳酸钠、棕榈酸钠、PCA钠、聚谷氨酸钠、可溶性胶原、失水山梨醇月桂酸酯、失水山梨醇油酸酯、失水山梨醇棕榈酸酯、失水山梨醇倍半油酸酯、失水山梨醇硬脂酸酯、山梨醇、大豆(glycine soja)油、鞘脂、角鲨烷、角鲨烯、硬脂酰胺MEA-硬脂酸酯、硬脂酸、硬脂氧基二甲基硅氧烷、硬脂氧基三甲基硅烷、十八烷醇、硬脂基甘草亭酸酯、硬脂基庚酸酯、硬脂基硬脂酸酯、葵花(helianthus annuus)籽油、甜杏仁(prunus amygdalus dulcis)油、合成蜂蜡、生育酚、生育酚乙酸酯、生育酚亚油酸酯、二十二烷酸甘油三酯(tribehenin)、新戊酸十三酯、硬脂酸十三酯、三乙醇胺、三硬脂酸甘油酯、脲、植物油、水、蜡类、小麦(triticum vulgare)胚油和依兰依兰(cananga odorata)油。
3.抗氧化剂
可以与本发明的组合物使用的抗氧化剂的非限定性例子包括乙酰半胱氨酸、抗坏血酸多肽、二棕榈酸抗坏血酸酯、甲基硅烷醇果胶脂酸抗坏血酸酯(ascorbyl methylsilanol pectinate)、棕榈酸抗坏血酸酯、硬脂酸抗坏血酸酯、BHA、BHT、叔丁基氢醌(t-butyl hydroquinone)、半胱氨酸、盐酸半胱氨酸、二戊基氢醌、二叔丁基氢醌、硫代二丙酸二(十六烷)酯(dicetylthiodipropionate)、二油基生育酚甲基硅烷醇、硫酸抗坏血酸酯二钠、硫代二丙酸二硬脂酸酯、硫代二丙酸二(十三)酯、没食子酸十二酯、异抗坏血酸、抗坏血酸酯类、阿魏酸乙酯、阿魏酸、没食子酸酯、氢醌、巯基乙酸异辛酯、曲酸、抗坏血酸镁、磷酸抗坏血酸镁、抗坏血酸甲基硅烷醇酯、天然的植物抗氧化剂如绿茶或葡萄籽提取物、去甲二氢化愈创木酸、没食子酸辛酯、苯基巯基乙酸、磷酸抗坏血酸生育酚酯钾、亚硫酸钾、没食子酸丙酯、醌类、迷迭香酸、抗坏血酸钠、亚硫酸氢钠、异抗坏血酸钠、焦亚硫酸钠、亚硫酸钠、超氧化物歧化酶、巯基乙酸钠、山梨醇缩糠醛、硫二甘醇、亚硫基二乙酰胺、亚硫基二乙酸、巯基乙酸、硫羟乳酸、硫代水杨酸、生育酚聚醚-5、生育酚聚醚-10、生育酚聚醚-12、生育酚聚醚-18、生育酚聚醚-50、生育酚、托可索仑(tocophersolan)、生育酚乙酸酯、生育酚亚油酸酯、烟酸生育酚酯、琥珀酸生育酚酯和亚磷酸三(壬基苯酯)。
4.结构剂
在其它的非限定性方面,本发明的组合物可以包括结构剂。在一些方面,结构剂帮助提供组合物的流变特征以助于所述组合物的稳定。在其它方面,结构剂也可以作为乳化剂或洗涤剂发挥作用。结构剂的非限定性例子包括硬脂酸、棕榈酸、十八烷醇、十六烷醇、二十二醇、硬脂酸、棕榈酸、具有平均大约1到大约21个环氧乙烷单位的十八烷醇的聚乙二醇醚、具有平均大约1到大约5个环氧乙烷单位的十六烷醇的聚乙二醇醚和它们的混合物。
5.乳化剂
在本发明的一些方面,所述组合物不包括乳化剂。然而,在其它方面,所述组合物包括一种或多种乳化剂。乳化剂能够减小相间的界面张力和改善乳剂的制剂和稳定性。所述乳化剂可以是非离子的、阳离子的、阴离子的和两性离子的乳化剂(见McCutcheon’s(1986);美国专利号5,011,681;4,421,769;3,755,560)。非限定性的例子包括甘油的酯类、丙二醇的酯类、聚乙二醇的脂肪酸酯类、聚丙二醇的脂肪酸酯类、山梨醇的酯类、脱水山梨醇酸酐的酯类、酸酸共聚物、葡萄糖的酯类和醚类、乙氧基化醚、乙氧基化醇、烷基磷酸酯、聚氧乙烯脂肪醚磷酸酯、脂肪酸酰胺、酰基乳酸酯、皂类、TEA硬脂酸酯、DEA油醇聚醚-3磷酸酯、聚乙二醇20脱水山梨醇单月桂酸值(聚山梨醇酯20)、聚乙二醇5大豆甾醇、硬脂醇聚醚-2、硬脂醇聚醚-20、硬脂醇聚醚-21,鲸蜡硬脂醇聚醚-20、PPG-2甲基葡糖醚二硬脂酸酯、鲸蜡醇醚-10、聚山梨醇酯80、十六烷基磷酸酯、十六烷基磷酸钾、十六烷基磷酸二乙醇胺、聚山梨醇酯60、硬脂酸甘油酯、PEG-100硬脂酸酯和它们的混合物。
6.含聚硅氧的化合物
在非限定性方面,含有聚硅氧的化合物可以包括聚合物家族的任何成员,其分子骨架由交互的硅和氧原子组成,具有结合到所述硅原子的侧基。通过改变-Si-O-的链长,侧基和交联,聚硅氧可以被合成为大量种类的材料。它们的稠度可以从液体到凝胶到固体变化。
可以用于本发明的含有聚硅氧的化合物,包括本说明书中所述的那些或本技术领域普通技术人员所知的那些。非限定性例子包括聚硅氧油类(例如,挥发的和不挥发的油类)、凝胶类和固体类。在某些方面,含有硅的化合物包括聚硅氧油类如聚硅氧烷。聚硅氧烷的非限定性例子包括二甲基硅氧烷、环甲基硅酮、聚硅氧烷-11、苯基三甲基硅氧烷、三甲基甲硅烷胺基二甲基硅氧烷(trimethylsilylamodimethicone)、硬脂氧基三甲基硅烷或这些化合物的混合物和其它的有机硅氧烷材料,它们为任何给定的比例,以获得期望的稠度和应用特性,这取决于所期望的施用(例如特定的区域,如皮肤、头发或眼睛)。“挥发性的聚硅氧油”包括具有低汽化热,即通常小于大约50cal每克聚硅氧油的聚硅氧。挥发性聚硅氧油的非限定性的例子包括:环甲基硅酮,如Dow Corning344Fluid、Dow Corning345Fluid、DowCorning244Fluid和Dow Corning245Fluid、Volatile Silicon7207(UnionCarbide Corp.,Danbury,Conn.);低粘度的二甲基硅氧烷,即具有大约50cst或以下粘度的二甲基硅氧烷类(例如,二甲基硅氧烷类,如Dow Corning200-0.5cst Fluid)。所述Dow Corning Fluids可从Dow Corning Corporation,Midland,Michigan获得。环甲基硅酮和二甲基硅氧烷在Third Edition of theCTFA Cosmetic Ingredient Dictionary(incorporated by reference)分别被作为环状二甲基聚硅氧烷化合物和用三甲基硅烷氧基单元端基封闭的全甲基化直链硅氧烷聚合物的混合物进行了描述。能够在本发明中使用的其它非限定性挥发性聚硅氧油包括从General Electric Co.,Silicone Products Div.,Waterford,N.Y.和SWS Silicones Div.of Stauffer Chemical Co.,Adrian,Michigan获得的那些。
7.精油
精油包括从草本、花类、树木和其它植物获得的油类。这样的油类基本上作为植物细胞间的微滴存在,并且可以通过本技术领域的普通技术人员所知的几种方法被提取(例如,蒸气蒸馏、冷吸(即通过使用脂肪提取)、浸渍、溶剂萃取或机械加工)。当这些类型的油类曝露于空气时,它们倾向蒸发(即,挥发性油)。结果是,虽然许多精油是无色的,但它们可能随着时间被氧化和变得更深。精油不能溶于水但能溶于醇、醚、固定油类(植物的)和其它有机溶剂。在精油中发现的典型的物理性质包括在大约160℃到240℃之间变化的沸点和介于大约0.759到大约1.096之间的密度。
精油基本上以从中发现的油的植物命名。例如,玫瑰油或薄荷油分别来自玫瑰或薄荷植物。可以被用于本发明的精油的非限定性例子包括芝麻油、澳洲坚果油、茶树油、月见草油、西班牙鼠尾草油、西班牙迷迭香油、芫荽油、百里香油、众香子油、玫瑰油、茴香油、香脂油(balsam oil)、香柠檬油(bergamot oil)、蔷薇木油(rosewood oil)、雪松油(cedar oil)、春黄菊油、鼠尾草油、香紫苏油、丁子香油(clove oil)、柏油、桉油、小茴香油、海茴香油、乳香油、老鹤草油、姜油、圆柚油、素芳花油、刺柏油、薰衣草油、柠檬油、柠檬草油、梨莓油(lime oil)、橘子油、甘牛至油(marjoram oil)、没药油、苦橙花油(neroli oil)、橙油、广藿香油、胡椒油、黑胡椒油、橙叶油(petitgrain oil)、松油、奥图玫瑰油(rose otto oil)、迷迭香油、檀香油、薄荷油、甘松油、岩兰油(vetiver oil)、冬青油或依兰依兰。本技术领域的普通技术人员所知的其它精油也被预期用于本发明中。
8.增稠剂
包括增稠剂或胶凝剂的增稠剂,包括能够增加组合物粘度的物质。增稠剂包括能够增加组合物粘度而基本不改变组合物内活性成分的功效的那些物质。增稠剂也可以增加本发明的组合物的稳定性。在本发明的一些方面,增稠剂包括氢化聚异丁烯或三羟硬脂精或二者的混合物。
可以用于本发明的附加增稠剂的非限定性例子包括羧酸聚合物、交联的聚丙烯酸酯聚合物、聚丙烯酰胺聚合物、多糖和树胶。羧酸聚合物的例子包括交联的化合物,其含有一个或多个来自丙烯酸、取代丙烯酸和这些丙烯酸和取代丙烯酸的盐和酯的单体,其中所述交联剂含有两个或以上的碳-碳双键并且衍生自多元醇(见美国专利号5,087,445;4,509,949;2,798,053;CTFA International Cosmetic Ingredient Dictionary,Fourth edition,1991,pp.12和80)。可商业获得的羧酸聚合物的例子包括卡波姆类(carbomers),它们是丙烯酸与蔗糖或季茂四醇的烯丙酯交联的均聚合物(例如,来自B.F.Goodrich的CarbopolTM900系列)。
交联聚丙烯酸酯聚合物的非限定性例子包括阳离子型和非离子型聚合物。例子在美国专利号5,100,660;4,849,484;4,835,206;4,628,078;4,599,379被描述。
聚丙烯酰胺聚合物的非限定性的例子(包括非离子型聚丙烯酰胺聚合物,其包括取代的支链或非支链聚合物)包括聚丙烯酰胺、异链烷烃和月桂醇聚醚-7、丙烯酰胺与丙烯酸取代的丙烯酰胺与取代丙烯酸的多嵌段共聚物。
多糖的非限定性例子包括纤维素、羧甲基羟乙基纤维素、乙酸丙酸纤维素羧酸酯、羟乙基纤维素、羟乙基乙基纤维素、羟丙基纤维素、羟丙基甲基纤维素、甲基羟乙基纤维素、微晶纤维素、纤维素硫酸钠和它们的混合物。另一个例子是烷基取代的纤维素,其中所述纤维素聚合物的羟基被羟烷基化(优选地羟乙基化或羟丙基化),以形成羟烷基化纤维素,接着进一步用C10-C30直链或支链的烷基通过醚键的连接将其修饰。基本上这些聚合物是C10-C30直链或支链的醇类与羟基烷基纤维素形成的醚类。其它有用的多糖包括硬葡聚糖,其包含(1-3)个连接的葡萄糖单元的直链,其中每三个单元含有(1-6)个连接的葡萄糖。
包括用于本发明的树胶的非限定性例子包括金合欢胶、琼脂、藻胶、藻酸、藻酸铵、支链淀粉、藻酸钙、角叉菜聚糖钙(calcium carrageenan)、肉碱(carnitine)、角叉菜聚糖、糊精、明胶、吉兰糖胶(gellan gum)、瓜耳胶、瓜耳胶羟丙基三甲基氯化铵(guar hydroxypropyltrimonium chloride)、锂蒙脱石(hectorite)、透明质酸、水合二氧化硅、羟基丙基壳聚糖、羟基丙基瓜耳胶、刺梧桐树胶(karaya gum)、海藻胶(kelp)、刺槐豆胶、纳豆胶(natto gum)、藻酸钾、角叉菜聚糖钾、聚乙二醇藻酸酯、菌核胶(sclerotium gum)、羧甲基葡聚糖钠、角叉菜聚糖钠、西黄蓍胶(tragacanth gum)、黄原胶和它们的混合物。
9.附加的化合物和药物
可以与本发明的组合物使用的附加化合物和药物的非限定性例子包括维生素(例如A、B、C、D、E和K)、微量金属(例如,锌、钙和硒)、抗刺激剂(例如,甾体类和非甾体类抗炎药)、植物提取物(例如,芦荟、春黄菊、黄瓜提取物、银杏、人参和迷迭香)、染料和色料成分(例如,D&C蓝4号、D&C绿5号、D&C橙4号、D&C红17号、D&C红33号、D&C紫2号、D&C黄10号、D&C黄11号等)、软化剂(即,有机酯类、脂肪酸类、羊毛脂及其衍生物、植物和动物油类和脂类、甘油二酯类和甘油三酯类)、抗菌剂(例如,三氯生和乙醇)和香料(天然的和人工的)。
H.试剂盒
发明者也预期了试剂盒在本发明的某些方面中的应用。例如,本说明书所述的任何组合物、化合物、试剂或成分可以被包括在试剂盒中。在非限定性例子中,试剂盒可以包括局部护肤组合物,该局部护肤组合物包括卡卡杜李提取物、巴西莓提取物或二者的组合。
试剂盒的容器可以包括瓶子、分配器、包装、隔室或其它类型的容器,组分可以放入其中。所述容器可以分配预定量的组分(例如,本发明的组合物)。所述组合物可以通过喷雾剂、气溶胶或液体形态或半固体的形态被分配。所述容器可以具有喷雾、泵或挤压机械装置。所述容器其表面可以包括标记。所述标记,例如,可以是文字、短语、缩写、图或符号。所述文字或短语可以是“Mary Kay,”“化妆品”“防晒剂”等。
当试剂盒由一种以上的组分时(它们可以被包装在一起),所述试剂盒一般也会含有第二个、第三个或其它附加的容器,所述附加组分可以被单独地放入其中。本发明的试剂盒也可以包括密闭存放所述组分的容器,用于销售。这样的容器可以包括注塑或吹塑的塑料容器,将期望的瓶子、分配器或包装保留在其中。
试剂盒也可以包括使用说明书,说明使用试剂盒组分以及任何其它组合物、化合物、药剂、成分或没有包括在试剂盒中的物体的使用。使用说明书可以包括可被实施的变体。例如,使用说明书可以包括对如何涂敷、使用和保持所述产品或组合物的解释、
实施例
包括以下实施例,以说明本发明的一些非限定性方面。本技术领域的普通技术人员将会理解,在以下实施例中公开的技术代表了发明者发现的在本发明的实施中良好发挥作用的技术。然而,本技术领域普通技术人员应该,基于本公开内容,理解在所公开的具体实施方式中可做出许多变化和这些变化仍然获得类似的或相似的结果,而不偏离本发明的精神和范围。
实施例1含有卡卡杜李提取物的组合物
本发明的含有卡卡杜李提取物的非限定性例子述于表1和2。
表1*
成分 | %浓度(按重量) |
相A | |
水 | 84.44 |
黄原胶 | 0.1 |
对羟基苯甲酸甲酯 | 0.15 |
对羟基苯甲酸丙酯 | 0.1 |
柠檬酸 | 0.01 |
相B | |
十六烷醇 | 4.0 |
硬脂酸甘油酯+PEG100 | 4.0 |
棕榈酸辛酯 | 4.0 |
二甲基硅氧烷 | 1.0 |
生育酚乙酸酯 | 0.2 |
相C | |
卡卡杜李提取物 | 2.0 |
*将黄原胶洒在水中并混合10分钟。随后加入相A的所有成分并加热到70-75℃。将相B的所有物质加到单独的烧杯中并加热到70-75℃。在70-75℃混合相A和相B。持续混合并允许组合物冷却到30℃。随后,在混合时加入相C的成分。
表2*
成分 | %浓度(按重量) |
相A | |
水 | 78.6 |
对羟基苯甲酸甲酯 | 0.2 |
对羟基苯甲酸丙酯 | 0.1 |
Na2EDTA | 0.1 |
牛油果脂 | 4.5 |
凡士林 | 4.5 |
甘油 | 4.0 |
丙二醇 | 2.0 |
Finsolve TN | 2.0 |
相B | |
Sepigel305 | 2.0 |
相C | |
卡卡杜李提取物 | 2.0 |
*向烧杯中加入相A的成分,并且在混合时加热到70-75℃。随后,将相B的成分加到相A并且在混合中冷却到30℃。随后在混合时加入相C的成分。
这些成分的衍生物和修饰物可被作为取代物使用。另外,具有相似生理活性的其它成分可被预期地作为取代物或作为附加的成分使用,它们可以与本发明的组合物一起使用。也可以预期的是,本发明的组合物可以包括基本不影响所述组合物的功效的成分。这样的成分可以被用于,例如,改变本发明组合物的外观、味道和/或气味。
实施例2卡卡杜李提取物作为抗氧化剂的生物学功效
在卡卡杜李提取物在(1)减少细胞已有的内部氧化的能力;和(2)将少外部氧化对细胞的伤害的能力方面,对卡卡杜李提取物作为抗氧化剂的能力进行了评价。
过氧化物分析:用过氧化物特异性的染料,2',7'-二氯荧光黄双乙酸酯(DCFH-DA)通过流式细胞分析仪测量细胞的过氧化物。DCFH-DA起始是非荧光性的,其很快地通过依赖酶的过程被浓缩在活细胞中。通过细胞的过氧化物修饰后,当被激光激发时,该染料显示强的绿色荧光。基础过氧化物的产生,是通过正常的细胞代谢机制所产生,将会诱导低水平的过氧化物特异性的细胞荧光的逐渐形成。这样,这种荧光在没有经过任何处理下的测量可以成为阴性对照用作比较目的。而且,细胞外过氧化物(即,外加的H2O2)能够容易地透过细胞膜,并导致细胞的过氧化物特异性荧光的快速和急剧的增加。该分析可以被用于表征出测试物对基础过氧化物水平的影响和/或细胞外过氧化物对影响细胞过氧化物水平的能力。如果测试物被用作抗氧化剂,该分析也可以用于确定该测试物能否穿过细胞膜以猝灭细胞内过氧化物或其是否仅仅影响细胞外的过氧化物水平。
人类成人表皮角质细胞被培养在37℃和5.0%CO2下的标准生长培养基中。当70-80%汇合时,用0.025%胰蛋白酶/EDTA将细胞从平板中转移。当细胞变圆时,从培养皿移出含有胰蛋白酶/EDTA的细胞并中和。离心细胞并将得到的沉淀重悬于培养基中,产生单细胞的悬浮液。通过将DCFH-DA(10mM终浓度)负载到培养的角质细胞以流式细胞分析仪测量细胞的过氧化物。细胞用浓度增加的植物提取物处理三次,接着用或不用外加的过氧化氢(60mM)处理。分析诱导或没有诱导的细胞过氧化物的水平。为了确定细胞的抗氧化剂的活性可被举例说明,利用了以TroloxTM(维生素E的类似物和已知的抗氧化剂)作为抗氧化剂应答的阳性对照。用流式细胞分析仪和平均荧光强度(MFI)测量出细胞的过氧化物特异性的荧光。利用在双参数光散射图上产生的闸门将碎片从分析中排除。这些实验重复三次,与未处理的对照相比,计算出氧化性伤害的减少百分数(图1)。卡卡杜李提取物减少了外部损害造成的氧化性伤害。
实施例3在卡卡杜李提取物存在下人类真皮成纤维细胞中胶原的产量
研究了卡卡杜李提取物增加人类真皮成纤维细胞的胶原产量的能力。
胶原产量方案:来自冷冻小瓶的正常的人类真皮成纤维(NHDF)细胞在组织培养瓶(T25瓶)中生长到半汇合。两汇合的T25瓶培养物被胰蛋白酶消化、洗涤、重悬到16ml并尽量的接种到96孔板(200μl/孔)(只接种到4–12列)。细胞被允许生长过夜或直到细胞达到100%汇合。达到汇合后,抽出废培养基并加入200μl含有或不含有感兴趣的样品的新鲜培养基(三次重复)。图2中的液体提取物是1.0%(20μl的100X贮备液)和0.1%(2μl的100X贮备液)的卡卡杜李提取物,并被稀释到终体积200μl的NHDF生长培养基中(注意液体提取物在含有10-20%变性酒精和>50%的1,3丁二醇中的重量百分比为20-30%)。通过水稀释制备10%的该提取物的贮备液(2-3%的果汁提取物),其进一步在分析中被稀释到1.0%和0.1%(0.2-0.3%和0.02-0.03%的卡卡杜李果汁提取物,基于初始的提取物的量)。一组细胞用最终浓度为18μg/ml的L-抗坏血酸(维生素C)进行三次重复处理,作为阳性对照,该L-抗坏血酸已知是一种能增加胶原产量的试剂。细胞在样品存在时在37℃/5%CO2下培养3天。收集上清液并冷冻在-80℃下,直到用原胶原肽(Procollagen Peptide)(PIP)试剂盒(Takara Bio Inc.)进行分析,该试剂盒被设计用于测量40到640ng/ml范围的原胶原肽。该系统中的细胞可以被预期产生至少3000ng/ml的原胶原肽(培养基对照)。组织培养上清液需要用包括在试剂盒中的样品稀释剂稀释1:100。随试剂盒提供的方案见下。提供了简短的说明:
·打开铝箔包装前,允许平板达到室温。将上清液缓慢地解冻到室温。
·加入1ml dH2O到瓶3:PIP标准–温柔混合,使用前,在室温下静置10分钟。
·加入11ml H2O到瓶2:抗体-POD缀合物-温柔混合并在使用前在室温下静置10分钟。
·根据方案手册的指导,制作标准曲线。
·用样品稀释剂(试剂盒提供)稀释所有上清液1:40。
·用多道移液器转移100μl的POD缀合物/孔。随后,加入20μl的稀释的标准物或样品/孔,三次重复。
·在37℃下温育(覆盖)3小时。
·用400μl的洗液(见方案小册子的完全洗涤说明)洗涤平板4次。
·加入100μl底物溶液/孔并在室温下温育15分钟。
·加入100μl终止液/孔。温柔轻拍平板混合。
·在1小时内用酶标仪在450nm下测量吸光度。
·用4参数曲线拟合绘制标准曲线。从标准曲线确定原胶原肽的浓度。从标准曲线获得的结果必须乘以稀释因子,得到原胶原肽的总ng/ml数。
在1%卡卡杜李提取物的存在下,与未处理的真皮细胞对照物相比,真皮细胞中的胶原产量显著地增加(图2)。
实施例4使用卡卡杜李提取物减少人类表皮角质细胞的炎症
用细胞因子阵列分析研究了卡卡杜李提取物对减少人类表皮角质细胞炎症的能力。
细胞因子阵列:人类表皮角质细胞被培养至70-80%汇合率。抽出平板中的培养基并加入0.025%胰蛋白酶/EDTA。当细胞变圆时,温柔轻拍培养皿以释放细胞。从培养皿中移出含有胰蛋白酶/EDTA的细胞并中和。在180xg下离心细胞5min。细胞形成颗粒,吸出上清。得到的颗粒被重悬于EpiLifeTM培养基中(Cascade Biologics)。细胞以大约10-20%的汇合率接种于6-孔平板中。当细胞汇合大约80%时,吸出培养基,向两个重复的孔中加入1.0ml的EpiLifeTM和12-乙酸13-豆蔻酸佛波酯(phorbol13-Myristate12-acetate)(“PMA”)(已知的炎症诱导剂)和测试物稀释物(即,1.0%(100μl的100X贮备液)和0.1%(10μl的100X贮备液)的上述第34段制备的卡卡杜李提取物被稀释到最终体积1ml的EpiLife Growth Medium中)。所述培养基被温柔地涡旋以确保充分混合。另外,含有或不含有附加PMA的1.0ml EpiLifeTM被加到对照孔中。定量给料后,接着将所述平板在37±1℃和5.0±1%CO2下温育大约5小时。经过该5小时的温育后,所有的培养基被收集在锥形管中,并冷冻在-70℃下,并且所述冷冻的培养基随后置在干冰上被运到负责人。具有三次重复阵列的16个抗细胞因子抗体的16衬垫-FAST片和实验对照均购自Whatman BioSciences。
在分析的当天,将16-衬垫杂交室结合到片上,将片放入FASTFrame(每架4片)进行处理。在室温下用70ml的S&S蛋白阵列封闭缓冲液(S&SProtein Array Blocking buffer)(Whatman Schleicher and Scheull)封闭阵列15分钟。除去封闭缓冲液,向每个阵列加入70ml的每种上清样品。在室温下,在温柔地搅动的情况下,温育阵列3小时。用TBS-T洗涤阵列3次。用70ml的抗体混合物处理阵列,该抗体混合物含有对应于各阵列捕获抗体的一种生物素化抗体。在室温下,在温柔地搅动的情况下,温育阵列1小时。阵列用TBS-T洗涤3次。用70ml含有链霉亲和素-Cy5缀合物的溶液,在室温下,在温柔地搅动的情况下,温育阵列1小时,用TBS-T洗3次,在去离子水中快速冲洗并干燥。
片在Perkin-Elmer ScanArray4000共焦荧光成像系统中成像。阵列图像保存为具有10微米像素分辨率的16-位TIF文件。图像用Imaging ResearchArrayVision软件分析。简而言之,通过扣除背景信号确定斑点强度。在各样品的斑点重复被平均的条件下,与合适的对照比较。Microsoft Excel和GraphPad Prism被用于附加的分析和数据表示。
某些炎症细胞因子的减少百分比见图3。尽管卡卡杜李提取物减少了与几种类型的细胞因子相关的炎症应答,但是该提取物特别有效地减少了IL-8和IL-6的炎症应答。接着,通过这种方式,可以观察到,卡卡杜李提取物和巴西莓提取物对炎症应答的减少是互补的(见图7)。
实施例5本发明含有巴西莓提取物的组合物的非限定性例子
本发明含有巴西莓提取物的组合物的非限定性例子示于表3和4。
表3*
成分 | %浓度(按重量) |
相A | |
水 | 84.44 |
黄原胶 | 0.1 |
对羟基苯甲酸甲酯 | 0.15 |
对羟基苯甲酸丙酯 | 0.1 |
柠檬酸 | 0.01 |
相B | |
十六烷醇 | 4.0 |
硬脂酸甘油酯+PEG100 | 4.0 |
棕榈酸辛酯 | 4.0 |
二甲基硅氧烷 | 1.0 |
生育酚乙酸酯 | 0.2 |
相C | |
巴西莓提取物 | 2.0 |
*将黄原胶洒在水中并混合10分钟。随后加入相A的所有成分并加热到70-75℃。将相B的所有物质加到单独的烧杯中并加热到70-75℃。在70-75℃混合相A和相B。持续混合并允许组合物冷却到30℃。随后,在混合时加入相C的成分。
表4*
成分 | %浓度(按重量) |
相A | |
水 | 78.6 |
对羟基苯甲酸甲酯 | 0.2 |
对羟基苯甲酸丙酯 | 0.1 |
Na2EDTA | 0.1 |
牛油果脂 | 4.5 |
凡士林 | 4.5 |
甘油 | 4.0 |
丙二醇 | 2.0 |
Finsolve TN | 2.0 |
相B | |
Sepigel305 | 2.0 |
相C | |
巴西莓提取物 | 2.0 |
*向烧杯中加入相A的成分并且混合时加热到70-75℃。随后,将相B的成分加到相A并且在混合中冷却到30℃。随后在混合时加入相C的成分。
实施例6巴西莓的生物学功效:作为抗氧化剂发挥作用
对巴西莓提取物作为抗氧化剂的能力,其在(1)减少细胞已有的内部氧化的能力;和(2)减少外部氧化对细胞的伤害的能力方面进行了评价。使用了实施例2中所述的过氧化物分析,其中H2O2、DCFH-DA染料和巴西莓提取物(取代卡卡杜李提取物)以相同的量被使用。
这些实验重复三次,计算氧化性伤害的减少百分比(图5)。巴西莓提取物减少了由于内部和外部损害造成的氧化性伤害。
实施例7在巴西莓李提取物的存在下人类真皮成纤维细胞中胶原的产量
研究了巴西莓提取物增加人类真皮成纤维细胞中胶原的能力。利用实施例3所述的胶原产量方案,使用相同量的巴西莓提取物取代卡卡杜李提取物。
在1%巴西莓提取物的存在下,与对照真皮细胞比较,真皮细胞中胶原的产量显著地增加(图6),但是少于图2所示的在相同量的卡卡杜李提取物的存在下所产生的胶原百分比。
实施例8用巴西莓提取物减少人类表皮角质细胞的炎症
用细胞因子阵列分析研究了巴西莓提取物减少人类表皮角质细胞炎症的能力。利用了实施例4的细胞因子分析,使用了巴西莓提取物取代卡卡杜李提取物。
一些炎症细胞因子的百分比减少可见于图6。尽管巴西莓提取物减少了与几种类型的细胞因子相关的炎症应答,但是该提取物特别有效地减少了IL-2和ICAM-6的炎症应答。所见的卡卡杜李提取物和巴西莓提取物对炎症应答的减少是互补的(见图7)。
实施例9包括卡卡杜李提取物和巴西莓提取物的本发明组合物的非限定性例子
含有卡卡杜李提取物和巴西莓提取物的本发明组合物的非限定性例子述于表5和6。
表5*
成分 | %浓度(按重量) |
相A | |
水 | 84.44 |
黄原胶 | 0.1 |
对羟基苯甲酸甲酯 | 0.15 |
对羟基苯甲酸丙酯 | 0.1 |
柠檬酸 | 0.01 |
相B | |
十六烷醇 | 4.0 |
硬脂酸甘油酯+PEG100 | 4.0 |
棕榈酸辛酯 | 4.0 |
二甲基硅氧烷 | 1.0 |
生育酚乙酸酯 | 0.2 |
相C | |
卡卡杜李提取物 | 1.0 |
巴西莓提取物 | 1.0 |
*将黄原胶洒在水中并混合10分钟。随后加入相A的所有成分并加热到70-75℃。将相B的所有物质加到单独的烧杯中并加热到70-75℃。在70-75℃混合相A和相B。持续混合并允许组合物冷却到30℃。随后,在混合时加入相C的成分。
表6*
成分 | %浓度(按重量) |
相A | |
水 | 78.6 |
对羟基苯甲酸甲酯 | 0.2 |
对羟基苯甲酸丙酯 | 0.1 |
Na2EDTA | 0.1 |
牛油果脂 | 4.5 |
凡士林 | 4.5 |
甘油 | 4.0 |
丙二醇 | 2.0 |
Finsolve TN | 2.0 |
相B | |
Sepigel305 | 2.0 |
相C | |
卡卡杜李提取物 | 1.0 |
巴西莓提取物 | 1.0 |
*向烧杯中加入相A的成分并且混合时加热到70-75℃。随后,将相B的成分加到相A并且在混合时冷却到30℃。随后在混合时加入相C的成分。
实施例10确定本发明的组合物的功效
本发明的组合物的功效可以通过本技术领域的普通技术人员所知的方法确定。以下是可以用于本发明的非限定性方案。应该知道的是,可以使用其它的检验方案,包括,例如客观的和主观的方案。
用Nova Dermal Phase Meter通过使用阻抗测量可以测量皮肤水分/水合。该阻抗仪测量皮肤含水量的变化。皮肤的外层具有不同的电特性。当皮肤干燥时,它导电力很差。当它更加水合时,导电性增加。结果,皮肤阻抗的变化(与导电性相关)可以被用于评价皮肤水合的变化。可以根据仪器的说明书在每个测试日对单位进行校准。也可以制造温度和相对湿度的标志法。可以如下评价受试者:在测量前,它们可以在具有确定湿度(例如,30-50%)和温度(例如,68-72℃)的房间中平衡。三个单独的阻抗读数可以在面部的各个侧面获得、记录和平均。可以使用阻抗仪上的T5装置,其每5秒钟平均适用于面部的阻抗值。变化可以统计方差和显著性来报告。
皮肤清晰度和雀斑和老人斑的减少可以用Minolta Chromometer评价。利用Minolta Chroma Meter的a*值,可以分析皮肤色泽的变化,以确定由于产品治疗导致的刺激能力。该a*值测量在红色区域的皮肤颜色的变化。这用于确定组合物是否诱导刺激反应。所述测量可以在面部的各个侧面进行,并平均为左边和右边的面部值。皮肤清晰度也可以用Minolta Meter测量。所述测量值是Minolta Meter的a*、b和L值的组合,并与皮肤亮度相关,与皮肤的光滑度和水合关联。如上所述获得皮肤读数。在一个非限定性的方面,皮肤清晰度可以被描述为L/C,其中C是色度,被定义为(a2+b2)1/2。
皮肤干燥、表面细线、皮肤光滑度和皮肤色调可以用临床分级技术评价。例如,皮肤干燥的临床分级可以通过五点的标准Kligman Scale确定:(0)皮肤是软的和湿的;(1)皮肤看上去正常,无可见的干燥;(2)皮肤摸上去感到有点干,接触没有可见剥落;(3)皮肤感到干、硬,并且具有白色的外观和一些脱皮;和(4)皮肤感到很干、粗糙,并具有白色的外观和脱皮。评价可以由两个临床医师单独做出,并平均。
皮肤色调的临床分级可以通过十点的模拟数值标准进行:(10)一致、浅粉褐色的均匀皮肤。用手持放大镜检查后,无黑色、红斑或鳞状碎片。皮肤的微观结构摸上去很一致;(7)不放大观察,均匀的皮肤色调。无鳞片区域,但是由于或色素沉着或红斑导致而有点变色。没有超过直径1cm的变色;(4)容易观察到皮肤变色和不均匀的肌理。轻微的脱皮。在一些区域触到皮肤粗糙;和(1)不均匀的皮肤着色和肌理。许多脱皮和变色区域,或色素沉着过度、红斑或黑斑。直径超过1cm的颜色不均匀的大区域。由两个临床医师单独评价并平均。
皮肤光滑的临床分级可以通过十点的模拟数值标准进行分析:(10)光滑,皮肤潮湿和闪光,手指拉过表面没有阻力;(7)有点光滑,有点阻力;(4)粗糙,摩擦后可见变化和阻力;和(1)粗糙、鳞状、不均匀的表面。评价由两个临床医师单独做出并平均。
皮肤光滑度和皱纹的减少也可以通过用Packman等(1978)公开的方法进行视觉评价。例如,在每个受试者观察,仔细评分和记录每个受试者的表面的面部线条(SFLs)的深、浅和总数。通过将数值因子乘以深/宽/长度因子得到数值得分。得到眼部和嘴部区域的(左边和右边)得分并加在一起作为总的皱纹得分。
用Hargens冲击仪测量皮肤的结实度,该仪器通过将小的弹体落到皮肤上并记录其最初的两次回弹峰值,评价皮肤的弹性和结实度。该冲击仪是一轻小的探针,其具有相对钝的尖(4平方mm的接触面积)。所述探针稍微穿透皮肤并得到测量值,这依赖于皮肤外层的性质,包括角质层和外表皮和一部分真皮层。
皮肤的软/柔软性可以用空气轴承电功率计(Gas BearingElectrodynamometer),一种测量皮肤应力/应变的仪器,来进行评价。皮肤的粘弹性与皮肤的保湿有关。通过用双面胶带将探针粘到皮肤表面,测量值可以在颊的预定位点获得。可以施加平行于皮肤表面的大约3.5gm的力量,准确测量移位皮肤。接着计算皮肤的柔软性并表达为DSR(动态弹簧钢性(Dynamic Spring Rate),gm/mm)。
皮肤上的细线和皱纹的外观可以用复制品进行评价,该复制品是皮肤表面的印痕。可以使用硅橡胶类材料。复制品可以通过成像分析技术进行分析。通过用形成受试者面部的硅复制品和用计算机成像分析系统分析复制品图像,细线和皱纹可见性的变化可被客观地定量。复制品可以取自眼部区域和颈部区域,并用数码相机用低角度的入射光拍照。该数码图像可用图像加工程序分析,确定细线或皱纹所覆盖的复制品。
皮肤的表面轮廓可以通过利用轮廓仪/记录针的方法测量。这包括或照明灯或拖拉记录针通过复制品表面。记录针的垂直位移可以通过距离传感器被输入到计算机中,并在扫描复制品的固定长度后,对皮肤轮廓的截面分析可以产生为二维的曲线。该扫描可以沿着固定的轴线重复任意次,产生皮肤的模拟3D图像。使用记录针技术,可以获得复制品的十个随机的截面,并组合产生平均值。目的包括Ra,它是所有粗糙度(高度)的算术平均值,它是通过整合与平均轮廓高度相关的轮廓高度计算获得的。Rt是最高的峰与最低的谷之间的最大垂直距离,和Rz是平均的峰幅减去平均的峰高。数值作为校准值以mm给出。设备应该在各自使用前通过扫描已知值的金属标准物进行校准。Ra值通过以下公式可以计算:Ra=标准粗糙度;lm=横向(扫描)长度;和y=相对于平均轮廓高度(x-轴)的轮廓位置的绝对值。
在其它的非限定性方面,本发明的所述组合物的功效可以通过用皮肤类似物如,例如MELANODERMTM,进行评价。黑素细胞,是皮肤类似物的细胞的一种,当曝露于L-二羟苯丙氨酸(L-DOPA),黑色素的前体时,呈阳性染色。皮肤类似物,MELANODERMTM,可以用各种含有本发明的组合物和增白剂的各种碱来处理,或单独用碱来处理作为对照。可选地,皮肤类似物的未处理的样品用作对照。
在本说明书中公开和要求的所有的组合物和/或方法,基于本公开内容,无需过度实验就能够被制备和实施。尽管本发明的组合物和方法已经按照具体的实施方式进行了描述,但是对本技术领域的普通技术人员显而易见的是,变体可以适用于此处所述的组合物和/或方法和所述方法的步骤或步骤顺序,而不偏离本发明的概念、精神和范围。更具体地说,显而易见的是,在化学上和生理学上都相关的一些药物可以取代此处所述的试剂,而可能获得相同或相似的结果。对本技术领域普通技术人员显而易见的所有这些相似的取代物和修饰被认为在由所附权利要求所限定的本发明的精神、范围和概念内。
参考文献
以下参考文献,在一定程度上它们提供了代表性的程序性的或其它的细节,它们与此处所述的那些细节互补,通过引用被特别地包括在本文中。
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Claims (24)
1.一种局部护肤组合物,其包括包含类黄酮的巴西莓提取物。
2.一种局部护肤组合物,其包括包含维生素C的卡卡杜李提取物和包含类黄酮的巴西莓提取物。
3.权利要求1-2任一项的局部护肤组合物,其中所述组合物是乳剂、膏、洗液、溶液、无水碱、或凝胶。
4.权利要求3的局部护肤组合物,其中所述组合物是乳剂。
5.权利要求2的局部护肤组合物,其中所述组合物包括重量百分比为0.05%到25%的卡卡杜李提取物。
6.权利要求1-2任一项的局部护肤组合物,其中所述组合物包括重量百分比为0.05%到25%的巴西莓提取物。
7.权利要求2的局部护肤组合物,其中所述组合物包括重量百分比为0.05%到25%的卡卡杜李提取物和重量百分比为0.05%到25%的巴西莓提取物。
8.权利要求1-2任一项的局部护肤组合物,其中所述组合物包括维生素、矿物质、必需脂肪酸、必需氨基酸、类黄酮和蛋白。
9.权利要求1-2任一项的局部护肤组合物,其中所述组合物被包含在一个容器中。
10.权利要求9的局部护肤组合物,其中所述容器分配预定量的所述组合物。
11.权利要求10的局部护肤组合物,其中所述组合物以喷雾剂被分配。
12.一种护肤产品,其包括权利要求1-2任一项所述的局部护肤组合物。
13.包括包含类黄酮的巴西莓提取物的局部护肤组合物在制备用于减少皮肤炎症的药物中的用途,其中所述组合物的局部施用减少皮肤中TNF-α、IL-8、IL-1b、IL-6和VEGF细胞因子的产生。
14.权利要求13的用途,其中所述组合物是乳剂、膏、洗液、溶液、无水碱、或凝胶。
15.权利要求14的用途,其中所述组合物是乳剂。
16.权利要求13的用途,其中所述组合物包括重量百分比为0.05%到25%的巴西莓提取物。
17.权利要求13的用途,其中所述组合物包括维生素、矿物质、必需脂肪酸、必需氨基酸、类黄酮和蛋白。
18.权利要求13的用途,其中所述组合物被喷雾到皮肤上。
19.权利要求13的用途,其中所述组合物被涂抹到皮肤上。
20.权利要求13的用途,其中所述组合物减少细胞的内部和外部氧化。
21.权利要求20的用途,其中所述细胞是人类表皮角质细胞。
22.包括包含类黄酮的巴西莓提取物的局部护肤组合物在制备用于增加细胞胶原的产生的药物中的用途。
23.权利要求22的用途,其中所述局部护肤组合物进一步包括包含维生素C的卡卡杜李提取物。
24.权利要求22或23的用途,其中所述细胞是人类真皮成纤维细胞。
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US76010306P | 2006-01-19 | 2006-01-19 | |
US60/760,103 | 2006-01-19 | ||
US76097706P | 2006-01-20 | 2006-01-20 | |
US76097906P | 2006-01-20 | 2006-01-20 | |
US60/760,979 | 2006-01-20 | ||
US60/760,977 | 2006-01-20 |
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