CN1154652A - 去屑组合物 - Google Patents
去屑组合物 Download PDFInfo
- Publication number
- CN1154652A CN1154652A CN95194450A CN95194450A CN1154652A CN 1154652 A CN1154652 A CN 1154652A CN 95194450 A CN95194450 A CN 95194450A CN 95194450 A CN95194450 A CN 95194450A CN 1154652 A CN1154652 A CN 1154652A
- Authority
- CN
- China
- Prior art keywords
- skin
- carbon atoms
- pharmaceutically acceptable
- time
- beauty treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
- A61K8/447—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof containing sulfur
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- A—HUMAN NECESSITIES
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Abstract
本发明涉及包含某些巯基化合物和某些两性离子表面活性剂组合的去屑组合物。本发明进一步涉及在哺乳动物皮肤上去屑和在哺乳动物皮肤上治疗粉刺的方法。
Description
技术领域
本发明涉及皮肤调理领域。具体地,本发明涉及通过从皮肤表面除去鳞屑而改善皮肤的柔软性或光滑性的方法。
背景
皮肤由两层组成:表皮(或护膜)和真皮。表皮是由分层的上皮组成的薄外层。表皮的最外层是由蛋白质填充的角蛋白,被薄的脂质层包围的平化细胞组成的角质层。细胞被认为是通过细胞间的蛋白质接合(桥粒)而互相连接的。在表皮的最深部分,基层的细胞分裂生长,将表皮的老细胞推向表面。当这些细胞外移时它们变平。表皮一般缺少血管并依赖真皮中的血管提供营养。越靠外的表皮细胞离营养供给越远,逐渐分化,将其蛋白质转化为角蛋白。这一角蛋白化导致细胞死亡。角蛋白是一不溶的蛋白物质,赋予角质层角状的坚固性。最外层的角质层细胞逐渐脱落并被更新的角蛋白化的细胞代替。
在正常皮肤中,角质层以单细胞或小的细胞层脱落。皮肤问题如干性皮肤,牛皮癣,鳞癣,头皮屑,粉刺,骨痂,光损伤的皮肤,老化的皮肤,和晒伤可被描述为角蛋白化的病症,其中在皮肤表面角质层细胞的脱落涉及正常、稚嫩、健康的皮肤。这类改变导致大的细胞群变为可见的皮肤屑,在表面或在滤泡或管和/或粗糙的组织中构建角蛋白材料到皮肤表面上。这些皮肤问题已知通过除去最外层角蛋白物质而改善。
由于前述原因,需要一种有效的药用于从哺乳动物皮肤的角质层除去表面的鳞屑。
本发明的一个目的是提供从哺乳动物的皮肤角质层除屑(除去屑)的表面组合物。
本发明进一步的目标是提供这样的组合物-它们比已有的组合物更轻柔并对皮肤更少刺激性。
提供除去哺乳动物皮肤上的皮屑的方法也是本发明的目的。
本发明包括如下的组合:
(a)一种或多种选自由N-乙酰基-L-半胱氨酸,甲硫氨酸,
谷胱甘肽,二硫苏糖醇,二硫赤藓糖醇和高胱氨酸组成的一
组巯基化合物和其美容和/或药学上可接受的盐;和
(a)R1是具有约9至约22个碳原子的未取代的,饱和或不饱和
的,直链或支链烷基;
(b)m是1至3的整数;
(c)n是0或1;
(d)R2和R3独立地为具有1至约3个碳原子的,未取代或被羟
基单取代的烷基;
(e)R4是具有1至约5个碳原子,未取代或被羟基单取代的,饱
和或不饱和的,直链或支链烷基;且
(f)X是CO2,SO3或SO4。这样的组合和组合物满足了用于皮肤去屑的灵验的,容易给药的药剂的需要,具有很小或没有不希望有的副作用。本发明也涉及在受影响或患有非正常角蛋白化的哺乳动物身上除去皮屑的方法,包括应用本发明的组合物。本发明进一步涉及治疗患有粉刺的哺乳动物的粉刺的方法。
本发明的组合物包含安全和有效量的巯基化合物与安全和有效量的两性离子表面活性剂,并和美容和/或药学上可接受的载体相结合。
本发明的这些和其它特征,各个方面和优点参考下面的描述和所附的权利要求将变得更易理解。
发明详述
已经意外地发现,某些巯基化合物和某些两性离子表面活性剂的组合显示出从哺乳动物的皮肤和头皮的角质层除去皮屑的能力,没有不希望有的副作用。本发明不限于任何特定的作用模式,人们相信本发明的组合通过影响皮肤表面的,降解细胞间的蛋白质连接(桥粒)的水解蛋白酶而起作用,这样引起细胞或皮屑脱落。本发明因而激活了在有问题的皮肤的表面上皮肤的自然去屑过程。
本文所用的“去屑”意指从表皮的最外层(角质层)脱落或除去皮屑。
本文所用的“治疗粉刺”意指预防,阻止和/或抑制在哺乳动物的皮肤中粉刺形成的过程。
本文所用的述语“烷基”,除非另外指明,意指含碳的链,(即,烃链),它可以是直链或支链的,取代的或未取代的,饱和或未饱和的。优选的烷基是饱和的,直链和未取代的。
本文所用的“巯基化合物”意指含有S-H基并可以贡献氢原子,选自如下组成的一组化合物:
b)谷胱甘肽,具有如下结构:
d)二硫赤藓糖醇,具有如下结构:
e)高胱氨酸,具有如下结构:
和
f)前述化合物的美容和/或药学上可接受的盐。
该组合物可包括一种或多种巯基化合物。“巯基化合物”的意思包括前述巯基化合物的美容和/或药学上可接受的盐。巯基化合物的美容和/或药学上可接受的盐包括但不限于,碱金属盐,例如钠,锂,钾和铷盐;碱土金属盐,例如,镁,钙和锶盐;无毒性重金属盐,例如,铝,和锌盐;硼盐;硅盐;铵盐;三烷基铵盐,例如,三甲基铵和三乙基铵;和四烷基翁盐。巯基化合物优选的美容和/或药学上可接受的盐包括Na+,K+,Ca++,Mg++,Al2(OH)5 +,NH4 +,(HOCH2CH2)3NH+,(CH3CH2)3NH+,(CH3CH2)4N+,C12H25(CH3)3N+和C12H25(C5H4N)3N+盐。更优选的巯基化合物的盐包括Na+盐和NH4 +盐。巯基化合物的合适盐描述于,例如,1994年3月22日颁发给Hillebrand的美国专利5296500,引作本文参考。
可用于本发明的优选的巯基化合物包括N-乙酰基-L-半胱氨酸,谷胱甘肽,二硫苏糖醇,二硫赤藓糖醇,前述化合物的美容和/或药理上可接受的盐,和任何前述化合物的混合物。最优选的巯基化合物是N-乙酰基-L半胱氨酸或其美容和/或药学上可接受的盐。
在结构(1)中,R1是具有约9约22个碳原子,未取代的,饱和或不饱和的,直链或支链烷基。优选的R1具有约11至约18个碳原子;更优选地约12至约16个碳原子;还更优选的约14至约16个碳原子。
在结构(1)中,m是整数1至3,优选2或3;更优选3。
在结构(1)中,n是0或1;优选地为0。
在结构(1)中,R2和R3独立地选自由具有1至约3个碳原子,未取代或被羟基单取代的烷基组成的一组。优选的R2和R3为CH3。
结构(1)中,X选自由CO2,SO3和SO4组成的一组。
在结构(1)中,R4选自由具有1至5个碳原子,饱和或不饱和,直链或支链,未取代或被羟基单取代的烷基。当X=CO2时,R4优选地具有1或3个碳原子,更优选1个碳原子。当X=SO3或SO4时,R4优选地具有约2至约4个碳原子,更优选地3个碳原子。
本发明优选的两性离子表面活性剂包括如下化合物:
a)鲸蜡基甜菜碱,具有如下结构:
b)硬脂基甜菜碱,具有如下结构:
c)可可酰胺基丙基甜菜碱,具有如下结构:
其中R是具有约9至约13个碳原子,未取代的,饱和的,直链烷基;
d)鲸蜡基丙基羟基sultaine(cetyl propyl hydroxy sultaine),具有如下结构
其中R具有9至约13个碳原子;和
f)山萮基甜菜碱,具有如下结构:一种或多种两性离子表面活性剂可被用于本发明。本发明更优选的两性离子表面活性剂包括鲸蜡基甜菜碱,硬脂基甜菜碱,可可酰胺基丙基甜菜碱,鲸蜡基丙基羟基sultaine或其混合物。本发明还更优选的两性离子表面活性剂包括鲸蜡基甜菜碱,硬脂基甜菜碱,可可酰胺基丙基甜菜碱或其混合物。两性离子表面活性剂还更优选鲸蜡基甜菜碱和/或硬脂基甜菜碱。本发明最优选的两性离子表面活性剂是鲸蜡基甜菜碱。
“两性离子表面活性剂”意思包括前述化合物美容和/或药学上可接受的盐。优选的美容和/或药学上可接受的盐包括如本文前面对巯基化合物所述的碱金属盐,碱土金属盐,无毒性重金属盐,硼盐,硅盐,铵盐,三烷基铵盐,和四烷基铵盐。
本文所用的“表面应用”意指直接涂于或抹在皮肤外面。
本文所用的“安全和有效量”意指足够量的所述化合物,组合物或其它物质在治疗条件下能够产生显著的正面修饰作用,但其量足够低,以避免从医学角度的严重副作用(以适当的利益/风险比)。安全和有效量的化合物,组合物或其它物质将随被治疗的特定状况,被治疗的患者的年龄和生理状况,病症的严重程度,治疗周期,协同治疗的性质,所用具体化合物,组合物或其它物质,所用的特定的美容和/或药学上可接受的载休,和在主治医师的知识和专长范围内的类似因素而变化。
本文所用的“包含”意指可以加入的不影响最终结果的其它步骤和成份。此术语包括术语“由……组成”和“基本由……组成”。
本文所用的,“美容和/或药学上可接受的”意指所述的适用于接触人和低级动物的组织的,没有过份的毒性,配合禁忌,不稳定性,刺激性,过敏反应等,并具有相称的适当利益/风险比的盐,药剂,医药,惰性成份或其它物质。
本文所用的“主要活性物”,和“主要活性剂”意指本文前面所述的至少一种巯基化合物和至少一种根据结构(1)的两性离子表面活性剂的组合。
本发明的组合物含有能够引起脱屑的安全和有效量的至少一种巯基化合物和至少一种根据本文前面所述的结构(1)的两性离子表面活性剂。组合物优选地包含约0.1%至约20%,更优选地约0.2%至约10%,还优选约0.5%至约5%的巯基化合物,和约0.1%至约10%,更优选约0.2%至约5%,还优选约0.5%至约2%的结构(1)的两性离子表面活性剂。
美容和/或药学上可接受的载体
本发明的组合物对生物体局部给药,即,通过直接将组合物涂或抹在主体的皮肤上。本发明的局部组合物包括适于对哺乳动物皮肤局部应用的组合物,该组合物包含安全和有效量的主要活性剂和美容和/或药学上可接受的局部载体。
短语“美容和/或药学上可接受的载体”,如本文所用的,意指适于对人或低级动物给药的一种或多种可共容的固体或液体填充稀释剂。本文所用的术语“可共容的”意指本发明组合物的成份可以与本发明的主要活性物互相混合,以没有在普通使用条件下实质上降低组合物的效力的相互作用的方式进行。当然,美容-和/或药学上可接受的载体必须有足够高的纯度和足够低的毒性以使它们适于对被治疗的人或低级动物给药。
可用于本发明的局部组合物可被制成各种产品类型。这些包括,但不限于,洗剂,乳膏,凝胶,贴剂(sticks),喷雾剂,软膏,糊剂,奶油冻和化妆品。这些产品类型可包含几种载体体系,包括但不限于溶液,乳化液,凝胶,固体,和脂质体。
配制成溶液的可用于本发明的局部组合物典型地包括美容和/或药学上可接受的含水或有机溶剂。短语“美容和/或药学上可接受的有机溶剂”指可以使主要活性物分散或溶于其中,并具有可接受的安全性质(例如,刺激性和敏感特性)的溶剂。水是优选的溶剂。合适的有机溶剂的例子包括:丙二醇,聚乙二醇(分子量200-600g/mol),聚丙二醇(分子量425-2025g/mol),甘油,1,2,4-丁三醇,山梨糖醇酯,1,2,6-己三醇,乙醇,异丙醇,山梨糖醇酯,丁二醇,和其混合物。这些可用于本发明的溶液优选地含有约80%至约99.99%的可接受的含水或有机溶剂。
如果可用于本发明的局部组合物被配制为气雾剂并以喷雾剂应用于皮肤,可将推进剂加到溶液组合物中。推进剂例如包括氯-氟代的低分子量烃。可用于本发明的推进剂的更完整的公开可在Sagarin所著的“化妆科学技术”(Cosmetics Science and Technology)第2版,第2卷,第443-465页(1972)找到。
可用于本发明的局部组合物可被配制为包含润肤剂的溶液。这类组合物优选地含有约2%至约50%的局部美容和/或药学上可接受的润肤剂。
本文所用的“润肤剂”指用于预防或缓解干燥的以及保护皮肤的物质。大量合适的润肤剂是已知的并可在本发明中使用。引作本文参考的Sagarin所著的“化妆科学技术”(Cosmetics Science and Technology)第2版,第1卷,第32-43页(1972)中记载了大量合适物质的例子。
洗剂可从溶液载体体系制造。洗剂典型地包含约1%至20%,优选地约5%至约10%的润肤剂;和约50%至约90%,优约60%至约80%的水。
可从溶液载体体系配制的其它类型的产品是乳膏。乳膏典型地包含约5%至约50%,优选约10%至约20%的润肤剂,和约45%至约85%,优选约50%至75%的水。
可从溶液载体体系配制的另一类产品是乳膏。乳膏可包含动物或植物油或半固体烃(含油的)的简单基质。乳膏也可包含吸水而形成乳化液的吸收乳膏基质。乳膏载体也可以是水溶性的。乳膏可包含约2%至约10%的润肤剂;和约0.1%至约2%的增稠剂。可用于本发明的增稠剂的更完整的公开可在Sagarin所著的“化妆科学技术”(Cosmetics,Science and Technology)第2版,第1卷,第72-73页(1972)中找到。
如果载体被配成乳化液,优选地约1%至约10%,更优选地约2%至约5%的载体体系包含乳化剂。乳化剂可以是非离子性的,阴离子性或阳离子性的。合适的乳化剂公开于,例如,颁发于1973年8月28日的Dickert等人的美国专利3755560;颁发于1983年12月20日的Dixon等人的美国专利4421769;和MC-Cutcheon′s Detergents andEmulsifiers.North American Edition,p317-324(1986)。
优选的乳化液具有低粘度(粘度约50厘沲或更小)。更优选的乳化液具有约10厘沲的粘度或更小。进一步更优选的乳化液具有约5厘沲或更小的粘度。高分子量硅氧烷可被用于这类乳化液中。当使用时,这类硅氧烷可以不实际降低两性离子表面活性剂效力的量被使用。优选的乳化液基本上不含高分子量硅氧烷。在这类乳化液中,因为不存在硅氧烷,在一些组合物中,在应用时可引起发泡,所以消泡组合物也优选地被加入。本组合物优选的乳化液基本上不含包藏剂,如凡士林,它似乎降低两性离子的作用。本组合物的优选乳化液含有湿润剂,如甘油。
用于清洁的本发明组合物优选地含有约1%至90%,更优选地约5%至约10%的美容和/或药学上可接受的表面活性剂。
清洁组合物的物理形态不是关键。组合物可被,例如,配制成梳妆棒(toilet bar),液体,香波,糊剂,或奶油冻。梳妆棒是最优选的,因为这是最常用于清洗皮肤的清洁剂。清洗掉的清洁组合物,如香波,需要适于将足够量的活性物沉积在皮肤和头皮上的输送系统。优选的输送系统包括不溶性复合物的使用。关于更完全的公开,见1989年5月30日颁发的Barford等人的美国专利4835148;其全文在此引作本文参考。
可用于本发明的清洁组合物的表面活性剂成份选自阴离子型,非离子型,两性离子型,两性的和两性表面活性剂,以及这些表面活性剂的混合物。这些表面活性剂对于洗涤专业的熟练技术人员是已知的。
可用于本发明的清洁组合物可非强制性地以其专业水平含有常用于清洁组合物中的物质。可能的表面活性剂的非限制性例子包括isoceteth-20,甲基椰子基牛磺酸钠(sodium methyl cocoyl taurate),甲基油酰基牛磺酸钠(sodium methyl olelyl taurate),和月桂基硫酸钠。见1989年1月24日颁发的Kowcz等人的美国专利4800197,其全文引作本文参考,例如可用于本文的表面活性剂。可用于本文的广泛的另外的表面活性剂的例子描述于Mc Cutcheon所著的“洗涤剂和乳化剂”(Detergents and Emulsifiers)North American Edition(1986),由Allured Publishingcorporation出版,其全文引作本文参考。
溶液,气雾剂,洗剂,软膏,乳膏,乳化液和清洁组合物包含安全和有效量的巯基化合物,优选约0.1%至约20%,更优选地约0.2%至约10%,还优选约0.5%至约5%巯基化合物。这类组合物也包含安全和有效量的两性离子表面活性剂,优选地约0.1%至约10%,更优选地约0.2%至约5%,还优选约0.5%至约2%的两性离子表面活性剂。优选的溶液,气雾剂,洗剂,软膏,乳膏,乳化液和清洁组合物更优选地也含有防腐剂,防腐增强剂,锌,和/或本文所述的锌盐。这些药剂可以本文所述的量被掺到前述制剂中。
本发明的组合物优选地被配成具有pH7或更低。这些组合物的pH值优选的范围为约2至约7,更优选地约3至约6,最优选地约4.5至约5.5。具有pH在约4.5至7的组合物与具有pH大于约8.5的相应组合物相比,倾向于显示更低的皮肤刺激性,更小的气味,和更大的稳定性。本发明的优选乳化液被配制成低pH值,优选地约2至约4,更优选地约3。
其它成份
本发明的组合物可含有其它成份,包括但不限于防腐剂,防腐增强剂,和除主要活性物外的活性物。然而,某些药剂可降低两性离子表面活性剂的活性,因而优选地被避免,或者如果使用,则以相对低的浓度使用。例如,游离脂肪酸,高分子量硅氧烷,包藏剂如凡士林,增稠剂如salcare和羟乙基纤维素可降低两性离子表面活性剂的活性,因而优选地不用于本组合物中。如果用这类药剂,它们将以相对低的浓度使用。另外,某些药剂可降低巯基化合物,特别是N-乙酰基-L-半胱氨酸在局部制剂中的活性。首先,例如通过化合物的微生物代谢,过量的微生物可降低巯基化合物的活性。其次,已发现甲醛可与巯基化合物化学反应而降低其活性。因而,当含有巯基化合物的组合物与甲醛或甲醛形成的防腐性或其它物质配制时,组合物在一定时间内与不含甲醛或能形成甲醛的化合物的相应制剂相比具有降低的活性。因此,希望提供含巯基化合物的组合物具有防腐效力,但不包括甲醛或形成甲醛的防腐剂或其它物质。
本发明的组合物因而优选地基本不含甲醛和当存在于组合物中时可形成或释放甲醛的物质,包括在组合物中可形成或释放甲醛的防腐剂。甲醛和在组合物中可形成或释放甲醛的物质另外在本文称为“甲醛供体”。本文所用的“基本上不含甲醛供体”意指没有可被检测到的甲醛供体,优选地没有甲醛供体。甲醛供体的存在可通过在组合物中由任何合适的分析技术,例如高压液相色谱侧定甲醛的存在而指示。这类供体的存在可由在一定时间内甲醛的产生而被初检或证实。
本发明的局部组合物优选地包含一种或多种防腐剂。优选的防腐剂是基本不含甲醛供体的。因而,优选用于本发明的防腐剂是无论在防腐过程或在不相关的过程中在组合物中不形成或释放甲醛的。相反地,形成或释放甲醛的防腐剂在组合物中无论在防腐过程或在不相关的过程中都形成或释放甲醛。
更优选的防腐剂包括苄基醇,对羟苯甲酸丙酯,对羟苯甲酸乙酯,对羟苯甲酸丁酯,对羟苯甲酸甲酯,对羟苯甲酸苄酯,对羟苯甲酸异丁基酯,苯氧基乙醇,乙醇,山梨酸,甲基氯代异噻唑啉酮,甲基异噻唑啉酮(含有甲基氯代异噻唑啉酮和甲基异噻唑啉酮的混合物的防腐剂是可以购买的,例如,从Rohm and Haas以Kathon C G得到),甲基二溴代戊二腈(商品,例如购自Calgon为Tektamer38),脱氢乙酸,邻苯基苯酚,亚硫酸氢钠,双氯酚,任何前述化合物的盐,和任何前述化合物的混合物。
还更优选的防腐剂选自由苄基醇,对羟苯甲酸丙酯,对羟苯甲酸甲酯,苯氧基乙醇,甲基氯代异噻唑啉酮,甲基异噻唑啉酮,苯甲酸,前述任何防腐剂的盐,前述任何化合物的混合物。
还更优选的防腐剂是苄基醇,对羟苯甲酸丙酯,对羟苯甲酸甲酯,苯氧基乙醇和其混合物。还更优选地,防腐剂是对羟苯甲酸丙酯和对羟苯甲酸甲酯与苄基醇和苯氧基乙醇之一或两者的混合物。除巯基化合物的稳定性外,这些混合物提供了宽的防腐效力,对使用者没有或只有极小的皮肤刺激的危险。最优选地,防腐剂是苄基醇,对羟苯甲酸丙酯和对羟苯甲酸甲酯的混合物。除了巯基化合物的稳定性和宽的防腐效力外,此混合物对使用者的皮肤刺激性的危险特别低。
前述基本上不含甲醛供体的防腐剂的应用更详细地描述于以Greg.G.Hillebrand和Marcia S.Schnicker的名字在1995年6月7日申请的,标题为“包含N-乙酰基-L-半胱氨酸的局部组合物”的未审美国专利申请中,其全文引作本文参考。前述防腐剂优选地以与刚才参考的专利申请中的组合物所述相同的量用于本发明的组合物中。
本发明的组合物优选地包含安全和有效量的防腐增强剂。本文所用的述语“防腐增强剂”意指其目的是用来增强防腐剂的活性的药剂。如本专业熟练技术人员应该理解的,防腐增强剂基本身并不提供足够的效力,它会增加防腐剂的效力。防腐剂效力的增加可包括螯合。可用于本发明的优选的防腐增强剂包括乙二胺四乙酸(EDTA),丁二醇,丙二醇,乙醇,和其混合物。当防腐剂包括对羟苯甲酸,例如对甲苯甲酸甲酯或丙酯时,EDTA是优选的防腐增效剂。这类增效剂的应用更详细地描述于前面参考和引用的,以Greg.G.Hillebrand和Marcia S.Schnicker的名字于1995年6月7日申请的,标题为“包含N-乙酰基-L-半胱氨酸的局部组合物”的未审美国专利申请中。防腐增效剂优选地以刚才参考的专利申请的组合物中所述的相同量用于本发明中。
本发明的组合物优选地含有锌或可与巯基化合物配位的锌盐。虽然没有从理论上说明,锌通过与由巯基化合物分解以痕量形成的异味的H2S配位而最可能除味。锌可以额外或另外增加羟基化合物的稳定性。锌盐以适于本发明的方式的应用被进一步描述于1994年3月22日颁发的Hillebrand的美国专利5296500中,该专利引作本文参考。
两性离子表面活性剂会降低组合物的粘度。因此,增稠剂可被用于本发明组合物中以增加组合物的稠度和/或将相分离的危险减至最小。增稠剂将与组合物的组分共容或否则以相对低水平被应用,使其不会明显地降低两性离子表面活性剂的效力。增稠剂的例子包括羟乙基纤维素(例如,从Aqualon of Wilmington,DE购买)和Salcare。
本发明的组合物可非强制性地包含可以不同方式发生作用以增强巯基化物和/或两性离子表面活性剂活性物的优点的其它活性物(因而,其它活性物应不会明显地降低巯基化合物或两性离子表面活性剂化合物的活性)。这类物质的例子包括,但不限于消炎剂,抗菌剂,抗雄性激素剂,防晒剂,遮阳剂,抗氧化剂/自由基清除剂,螯合剂,去头屑剂,和水杨酸。A,消炎剂
消炎剂可被包括在与第一活性物一起的活性物,以达到更好的活性。安全和有效量的消炎剂可被加入用于本发明的组合物中,优选地为组合物的约0.1%至约10%,更优选地约0.5%至约5%。被用于组合物中的消炎剂的精确量取决于所用的特定消炎剂,因为这类药剂的效力变化很大。
甾类消炎剂,包括但不限于,皮质甾醇如氢化可的松,羟基去炎松,α-甲基地塞米松,磷酸地塞米松,二丙酸氯地米松,戊酸氯氟美松,丙缩羟强龙,去氧米松,酯酸去氧皮甾酮,地塞米松,二氯去氧强的松,二乙酸二氟松,特戊酸二氟米松,fluadrenolone,氟二氯松,氟氢可的松,特戊酸氟地塞米松,fluosinolone acetonide,醋酸肤轻松,flucortinebutylesters,氟考龙,醋酸氟甲叉龙,丙酮缩氟氢羟龙,氯氟松,醋酸氢化可的松,丁酸氢化可的松,甲强龙,丙酮缩去炎松,可的松,去氧可的松,flucetonide,氟氢可的松,双醋二氟检,fluradrenoloneacetonide,6α-甲-11β-羟孕酮,戊酮缩去炎松,苯乙酮缩去炎松,倍他米松和其酯的平衡,氯强的松,醋酸氯强的松,氯氟吐龙,clescinolone,二氯去氧强的松,醋丁二氟龙,氟二氯松,氟甲龙,醋酸甲氟龙,特戊酸氢化可的松,环戊基丙酸氢化可的松,氢可松氨酯,甲基强的松,对氟米松,强的松龙,强的松,二丙酸氯地米松,去炎松,和其混合物可被使用。可使用的优选的甾类消炎剂是氢化可的松。
可用于本发明组合物的第二类消炎剂包括非甾类消炎剂。在此类中包括的各种化合物对于熟练的专业人员是公知的。对于非甾类消炎剂的化学结构,合成,副作用,等等,可以参考标准教科书,包括“消炎和抗风湿药”(Anti-inflammatary and Anti-Rheumatic Drugs)(K.D.Rainsford编著,卷I-III,CRC出版,Boca Raton(1985)),和“消炎药剂的化学和药理学”(Anti-inflammatory Agents Chemistry andPharmacology)第1册(R.A.Scherrer等人编著,Academic Press,New York(1974))。
可用于本发明组合物中的具体非甾类抗炎剂包括,但不限于:
1)奥昔卡姆(oxicams),如吡氧噻嗪,异噻酰胺,替诺西康,舒多昔康,和CP-14304;
2)水杨酸酯,如阿斯匹林,水杨酰水杨酸,扑炎痛,trilisate,safapryn,solprin,二氟苯水杨酸,和芬度柳;
3)乙酸衍生物,如二氯苯胺苯乙酸,芬氯酸,消炎痛,苏灵大,甲苯酰吡咯乙酸,伊索克酸,呋罗芬酸,硫平酸,齐多美辛,阿西美辛,芬替酸,佐美酸,clindanac,奥昔平酸,联苯乙酸和酮咯酸;
4)灭酸类,如甲灭酸,甲氯灭酸,氟灭酸,氮氟灭酸,和甲磺灭酸;
5)丙酸衍生物,如异丁苯丙酸,甲氧萘丙酸,苯噁丙芬,氟联苯丙酸,苯酮苯丙酸,苯氧苯丙酸,联苯丁酮酸,茚酮苯丙酸,吡丙芬,卡咯芬,噁丙嗪,普拉咯芬,咪咯芬,硫噁咯芬,噻丙吩,阿明咯芬,和噻咯芬酸;和
6)吡唑类,如保泰松,羟基保泰松,戊烯保泰松,炎爽痛,和三甲保泰松。
这些非甾类抗炎剂的混合物也可被应用,以及这些药剂的美容和/或药学上可接受的盐和酯。例如,依托芬那酯,氟灭酸衍生物,对于局部应用特别有用。对于非甾类抗炎剂,异丁苯丙酸,甲氧苯丙酸,氟灭酸,甲灭酸,甲氯灭酸,吡氧噻嗪和联苯乙酸是优选的;异丁苯丙酸,甲氧苯丙酸,和氟灭酸是优选的。
最后,所谓“天然的”消炎剂可用于本发明的方法中。例如,小烛树脂,α-红没药醇,aloe vera,Manjistha(从Commiphora属,尤其是Commiphora Mukul的植物提取),可被应用。B.维生素A类
在可用于本发明的优选的去屑组合物中,一种或多种维生素A类,优选地视黄醇或视黄酸,更优选地视黄酸,被包括为与主要活性剂一起为活性物。含有维生素A类增加了组合物的去屑优点。安全和有效量的维生素A类可被加到可用于本发明的组合物中,优选地为组合物的约0.001%至约0.5%,更优选地约0.01%至约0.1%。本文所用的“维生素A类”包括所有天然和/或合成的维生素A类或在皮肤中具有维生素A的生物活性的视黄醇类化合物,以及这些化合物的几何异构体和立体异构体,如全反式视黄酸和13-顺-视黄酸。C.抗菌剂
在可用于本发明的优选组合物中,抗菌剂被包括为与主要活性剂一起的活性物。抗菌剂的包括增加了组合物的去屑优点。本文所用的“抗菌剂”意指可以杀灭微生物,防止微生物的发展或防止微生物的病原作用的化合物。
安全和有效量的抗菌剂可被加到可用于本发明的组合物中,优选地为组合物的约0.001%至约5%,更优选地约0.01%至约0.2%,还更优选地约0.05%至约1%。可用于本发明的优选的抗菌剂是过氧化苯甲酰,红霉素,四环素,氯林可霉素,壬二酸,和硫间苯二酚。D.抗雄性激素剂
在可用于本发明的优选组合物中,抗雄性激素剂被包括为与主要活性剂一起的活性物。本文所用的“抗雄性激素剂”意指可以通过在其靶器官中干扰雄性激素的作用而克服与雄性激素相关的病症。本发明的靶器官是哺乳动物的皮肤。E.防晒剂和遮阳剂
暴露于紫外光可导致角质层的过度剥落。因此,在可用于本发明的优选组合物中,防晒剂或遮阳剂包括为与本发明的主要活性物一起的活性物。合适的防晒剂或遮阳剂可以是有机或无机的。
广泛的常用防晒剂适用于与去屑剂结合。Sagarin,et al.,在Cosmetics Science and Technology的Chapter VIII,P189 ef seq.中披露了大量合适的药剂,引作本文参考。具体的合适防晒剂包括,例如:对氨基苯甲酸,其盐和其衍生物(乙基,异丁基,甘油基酯;对-二甲基氨基苯甲酸);氨茴酸酯(即,邻氨基苯甲酸酯;甲基,基,苯基,苄基,苯乙基,里哪基,萜品基,和环己烯基酯);水杨酸酯(正戊基,苯基,辛基,苄基,孟基,甘油基,和二丙二醇酯);肉桂酸衍生物(基和苄基酯,苯基肉桂腈;丁基肉桂酰基丙酮酸酯);二羟基肉桂酸衍生物(繖形酮,甲基繖形酮,甲基乙酰繖形酮);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);烃类(二苯基丁二烯,茋);二亚苄基丙酮和亚苄基乙酰苯;萘酚磺酸盐(2-萘酚-3,6-二磺酸和2-萘酚-6,8-二磺酸的钠盐);二羟基萘甲酸和其盐;邻-和对-羟基联苯基二磺酸盐;香豆素衍生物(7-羟基,7-甲基,3-苯基);二唑类(2-乙酰基-3-溴代吲唑,苯基苯并唑,甲基萘并噁唑,各种芳基苯并噻唑类);奎宁盐(硫酸氢盐,硫酸盐,氯化物,油酸盐,和单宁酸盐);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酮;尿酸和vilouricacid;单宁酸和其衍生物(例如六乙基醚);(丁基carbotol)(6-胡椒基)醚;氢醌;二苯酮类(羟苯,磺异苯酮,二羟苯酮,苯并间苯二酚,2,2′4,4′-四羟基二苯酮,2,2′-二羟基-4,4′-二甲氧基二苯酮,辛苯酮;4-异丙基二苯甲酰基甲烷;丁基甲氧基二苯甲酰基甲烷;氟双苯丙烯酸乙酯;[3-(4′-甲基苄亚基硼烷-2-酮)和4-异丙基二苯甲酰基甲烷。
其中,2-乙基己基-对-甲氧基肉桂酸酯,4,4′-叔丁基甲氧基二苯甲酰基甲烷,2-羟基-4-甲氧基二苯酮,辛基二甲基-对-氨基苯甲酸,鞣酰基三油酸酯,2,2-二羟基-4-甲氧基二苯酮,乙基-4-(双(羟丙基))氨基苯甲酸酯,2-乙基己基-2-氰基-3,3-二苯基丙烯酸酯,2-乙基己基水杨酸酯,对氨基苯甲酸甘油基酯,3,3,5-三甲基环已基水杨酸酯,甲基氨茴酸酯,对二甲基氨基苯甲酸或氨基苯甲酸酯,2-乙基己基-对-二甲基氨基苯甲酸酯,2-苯基苯并味唑-5-磺酸,2-(对-二甲基氨基苯基)-5-磺酸苯并唑甲酸和这些化合物的混合物是优选的。
更优选的可用于本发明中的组合物的防晒剂是2-乙基己基-对-甲氧基肉桂酸酯,丁基甲氧基二苯甲酰基甲烷,2-羟基-4-甲氧基二苯酮,辛基甲基-对氨基苯甲酸和其混合物。
也在本组合物中特别有用的是如在1990年6月26日颁发给Sabatelli的美国专利4937370,和1991年3月21日颁发给Sabatelli和Spirnak的美国专利4999186中披露的防晒剂,两篇文献都引作本文参考。其中所披露的防晒剂在一个分子内具有两个不同的发色团部分,它显示不同的紫外辐射吸收光谱。发色团部分的一个主要吸收在UVB辐射区,而另一个在UVA区强吸收。
这些防晒剂优选的成员是2,4-二羟基二苯酮的4-N,N-(2-乙基己基)甲基氨基苯甲酸酯;N,N-二-(2-乙基己基)-4-氨基苯甲酸与4-羟基二苯甲酰基甲烷的酯;4-N,N-(2-乙基己基)甲基氨基苯甲酸与4-羟基二苯甲酰基甲烷的酯;2-羟基-4-(2-羟基乙氧基)二苯酮的4-N,N-(2-乙基己基)甲基氨基苯甲酸酯;4-(2-羟基乙氧基)二苯甲酰基甲烷的4-N,N-(2-乙基己基)甲基氨基苯甲酸酯;2-羟基-4-(2-羟基乙氧基)二苯酮的N,N-二-(2-乙基己基)-4-氨基苯甲酸酯;和4-(2-羟基乙氧基)二苯甲酰基甲烷的N,N-二-(2-乙基己基)-4-氨基苯甲酸酯和其混合物。
合适的无机防晒剂或遮阳剂包括金属氧化物,例如氧化锌和二氧化钛。
安全和有效量的防晒剂可在本发明的组合物中用作添加的活性物。防晒剂必须与主要活性剂共容。组合物优选地包含约1%至约20%,更优选地约2%至约10%的防晒剂。精确的量取决于所选的防晒剂和需要的太阳保护因子(SPF)。
一种药剂也可被加到本发明的组合物中以改进那些组合物的皮肤直接性尤其是增强其对被水洗掉或擦掉的阻力。可以提供此优点的优选药剂是乙烯和丙烯酸的共聚物。包含此共聚物的组合物披露于1987年5月5日颁含发给Brock的美国专利4663157中,该文献引作本文参考。F.抗氧化剂/自由基消除剂
当巯基化合物(例如,谷胱甘肽)本身给予组合物抗氧化性质时,优选的本发明组合物包括抗氧化剂/自由基消除剂作为除主要活性剂之外的活性剂。抗氧化剂/自由基清除剂通过对可以引起角质层增加剥落的UV辐射提供额外保护而增强去屑优点。
安全和有效量的抗氧化剂/自由基清除剂可被加到可用于本发明的组合物,优选地为组合物的约0.1%至约10%,更优选地约1%至约5%。
抗氧化剂/自由基清除剂如抗坏血酸(维生素C)和其盐,生育酚(维生素E),生育酚山梨酸酯,生育酚的其它酯,丁基化的羟基苯甲酸和其盐,6-羟基-2,5,7,8-四甲基苯并二氢吡喃-2-羧酸(以商品名Trolox购买到),棓酸和其烷基酯,尤其是棓酸丙酯,尿酸和其盐和烷基酯,山梨酸和其盐,脂肪酸的抗坏血酸酯,胺类(例如,N,N-二乙基羟基胺,氨基胍),和二羟基富马酸和其盐可被使用。优选的抗氧化剂/自由基清除剂选自生育酚山梨酸酯和生育酚的其它酯。G.螯合剂
在优选的本发明去屑组合物中,螯合剂被包括为与主要活性剂一起的活性物。本文所用的“螯合剂”意指可以通过形成配合物从体系中除去金属离子使金属离子不能够容易地参与或催化化学反应的活性剂。螯合剂的包括通过对可以引起过量皮屑的UV辐射提供额外的保护而增加组合物的去屑优点。
安全和有效的螯合剂可被加到本发明的组合物中,优选地为组合物的约0.1%至约10%,更优选地约1%至约5%。可用于组合物中的螯合剂披露于1990年11月27日提交的Bissett,Bush和Chatterjee等人的美国专利申请序号619805(它是1988年10月4日提交的美国专利申请序号251910的继续);1990年4月26日提交的Bush和Bissett的美国专利申请序号514892;和1991年2月25日提交的Bush,Bissett和Chatterjee的美国专利申请序号657847;所有它们引作本文参考。可用于本发明组合物的优选的螯合剂是糠偶酰二肟和其衍生物。H.去头屑活性物
在优选的配制用于头皮的本发明组合物中,去头屑剂被包括为与主要活性剂一起的活性物。去头屑剂通过进一步预防和治疗头皮的剥落作用而增强本发明的去头屑优点。特别优选的去头屑剂是吡啶硫酮锌。I.水杨酸
在优选的本发明组合物中,水杨酸被包括为与主要活性剂一起的活性物。优选地,组合物包括约0.1%至约10%,更优选地约0.2%至5%,也优选地约0.5%至约2%水杨酸。
特别优选的本发明组合物包括巯基化合物,两性离子化合物和水杨酸,更优选地以前述对各组分的量。在这类组合物中,巯基化合物优选地为N-乙酰基-L-半胱氨酸(包括其美容和/或药学上可接受的盐),而两性离子表面活性剂优选地为鲸蜡基甜菜碱或硬脂基甜菜碱,更优选地为鲸蜡基甜菜碱(包括这些化合物的美容和/或药学上可接受的盐)。
本发明的组合物一般通过常规方法如制造局部用组合物专业已知的方法制备。这类方法典型地包括在有或没有加热,冷却,真空的条件下,将各成分混合为相对均一的状态。
为了使巯基化合物的稳定性最佳化,本发明的组合物应从避免巯基化合物的简单空气氧化的方式生产,包装和贮存,这在本专业是公知的。因而,在生产,包装和贮存期间组合物对空气的暴露应被减至最小。
局部用组合物的输送方法
可用于本发明方法的局部用组合物可以各种输送装置输送。下面是两个非限制性实施例。
含药的清洁垫
可用于本发明的组合物可被掺入含药的清洁垫中。优选地这些垫包含约50%至约75%重量的一或多层非织物纤维材料,和约20%至50%重量的可从包含羟含基酸,包含水杨酸和本发明两性离子表面活性剂,或这类表面活性剂的混合物的非纺织纤维材料输送的液体组合物。这些垫详细地描述于1990年1月2日颁发给Thaman等人的美国专利4891228;和1990年1月2日的颁发给Thaman等人的美国专利4891227中;两篇文献都全文引作本文参考。
发药装置
可用于本文的组合物也可被掺入一软头或柔软的发药装置中,并从其中输送出来。这些装置可用于控制组合物向皮肤表面的输送,并且有治疗组合物本身从来不需要使用者直接处理的优点。这类装置的非限制性例子包含包括嘴,敷用器,将敷用器装在容器的嘴上的工具,和一个正常关闭的对压力反应的阀门,用于将压力施加于阀门时使流体从容器流向敷用器的流体容器。流体包含羟基酸,包含水杨酸和本发明两性离子表面活性剂,或这类表面活性剂的混合物。
该阀门可包括一个由弹性流体不渗透材料形成的隔膜,带有多个非交叉的弓形切口,其中各个切口具有一个与至少一个其它切口交叉的底部,并且其中各个切口与其本身的底部不是交叉的,其中有一个用于将阀门安装在容器的敷用器之外的工具。这些敷用器装置的例子描述于1987年9月15日颁发给Schwartzman的美国专利4693623;1987年9月15日颁发给Schwartzman的美国专利4620648;1972年6月13日颁发给Harker等人的美国专利3669323;1968年12月24日颁发给Schwartzman的美国专利3418055;和1968年12月12日颁发给Schwartzman的美国专利3410645;所有这些文献都引作本文参考。可用于本文的敷用器的例子是从Dab-o-Matic,Mount Vernon,Ny购买的。
去屑和治疗粉刺的方法
本发明涉及从哺乳动物的角质层除去皮屑的方法。这类方法包含以有效量的本发明组合物局部施用于皮肤或头皮。本文所用的术语“有效量”意指足够提供皮屑除去作用的量。该组合物可以在适当的间隔内施用几天,几周,几月或几年:从约一天三次至约每三天一次,优选地约一天两次至每隔一天一次,还优选约一天一次,直到达到满意的去屑作用。
本发明组合物还可有一种或多种如下应用:减少大毛孔的出现,降低皮肤颜色方面的缺陷和/或瑕庇,缓解干燥,消除干燥的粗斑,改善皮肤保持水份的能力和/或保护其免受环境的压力,减少细线和皱纹的出现,改善外观和皮肤色调,增加皮肤弹性和/或柔软性,增加皮肤光泽和透明,和/或增加皮肤恢复程序。
典型地,在各种应用中,皮肤或头皮的有效涂抹通过施用每种约0.004mg/cm2至约0.1mg/cm2一种或多种巯基化合物,和一种或多种两性离子表面活性剂,更优选约0.02mg/cm2至约0.06mg/cm2,也优选地约0.04mg/cm2这些材料。
实施例
下列实施例进一步说明和证明本发明范围内的方案。这些给出的实施例只是用于举例说明而不限制本发明,其许多变体可能不脱离本发明的精神范围。
实施例I
通过用常规混合技术混合下列组分制备局部组合物。
成份 %重量
水 q.s.
三乙醇胺 0.66
鲸蜡基甜菜碱 6.66
EDTA二钠 0.01
乙醇(95%) 40.00
N-乙酰基-L-半胱氨酸 2.00
上述组合物每天以足以使每cm2皮肤沉积2mg组合物的剂量用于面部以除去皮屑。作为去屑过程,施用被减少为隔天一次。
实施例II
通过用常规混合技术将下列成分混合制备清洁组合物:
成分 %重量
水 q.s.
EDTA四钠 0.12
鲸蜡基甜菜碱 3.33
甲基椰子基牛磺酸钠 41.67
(Soclium methyl cocoyl taurate)
可可酰胺基丙基羟基sultaine 6.00
(Cocoanvidopropyl hydroxy sultaine)
水杨酸 2.00
可可酰氨基丙基甜菜碱 1.43
羟丙基甲基纤维素 0.50
谷胱甘肽 2.00
香料 0.12
清洁组合物用于面部一天两次治疗粉刺。足以使每cm2皮肤沉积3mg组合物的量被使用。随着存在的粉刺减退,频率被减为一天一次。
实施例III
通过常规混合技术将成份混合制备下列头发调色剂:
成分 %重量
三乙醇胺月桂基硫酸盐 17.0
椰子二乙醇酰胺 2.0
羟丙基甲基纤维素1 0.2
玉米糖浆(80%固体)2 30.0
二甲基聚硅氧烷 1.0
阳离子纤维素3 0.5
乙醇(SDA40) 9.0
乙烯基羧基聚合物4 0.7
甲硫氨酸 1.5
可可酰氨基甜菜碱 3.5
香料,着色剂,防腐剂 1.0
水 q.s.
酸或碱至pH6.5
1Methocel E4M(Dow Chemical)
242葡萄糖等价物(Staley1300)
3聚合物JR400
4Carbopol941(BF Goodrich)
组合物每隔天用于头皮治疗头屑。每cm2皮肤5mg组合物的剂量被施用,然后洗掉。
实施例IV
通过常规混合技术将各成份混合制备下列局部凝胶:
成份 %重量
醇SD-40(95%) 40.00
高胱氨酸 2.00
EDTA二钠 0.005
鲸蜡基甜菜碱 6.66
水 q.s.
凝胶以每cm2皮肤0.2mg组合物的剂量每日三次用于面部以除去皮屑。作为去屑过程,施用可被减至一天一次。
实施例V
通过根据常规混合技术将各成份混合制备下列洗剂:
成份 %重量
水 q.s.
甘油 10.0
凡士林 2.5
鲸蜡醇 1.8
Cyclomethicone和Dimethicone Copolyol 1.5
硬酯醇 1.2
棕榈酸异丙酯 1.0
Dimethicone 0.5
氢氧化钠 0.34
羊毛脂酸 0.25
聚乙二醇-100硬酯酸酯 0.25
硬酯酸 0.25
对羟苯甲酸甲酯 0.2
二氧化钛 0.15
EDTA 0.1
N-乙酰基-L-半脱氨酸 12.0
可可酰胺丙基甜菜碱 5.0
上述洗剂每天以每cm2皮肤75mg组合物的剂量施用于手上。作为去屑过程,施用频率可被减至每两天一次。
实施例VI
通过常规混合技术将下列成份混合,制备下列乳化液:
成份 %重量
水 q.s.
PPG-14丁基醚 8.0
鲸蜡基甜菜碱 2.0
甘油 4.0
N-乙酰基-L-半胱氨酸 10.0
硬酯醇 1.5
Salcare SC95 1.5
鲸蜡醇 1.5
Dimethicone 1.0
硅胶(DC消泡) 0.5
Steareth-21 0.45
Steareth-2 0.05
EDTA四钠 0.02
上述洗剂每天以每cm2皮肤60mg的剂量施用于面部。作为去屑过程,施用频率可被减为每两天一次。
实施例VII
从下面组分制备皮肤雪花膏。
成份 相码 产品中的重量%
无菌水 A 54.53
EDTA二钠 A 0.050
对羟苯甲酸甲酯 A 0.150
甘油 A 3.00
Natrasol 330Plus A 0.200
(被Aqualon修饰的羟乙基纤维素)
聚丙二醇-15硬酯基醚 B 3.250
对羟苯甲酸丙酯 B 0.100
鲸蜡醇 B 0.559
硬酯醇 B 2.028
山萮醇 B 0.221
Steareth-21 B 0.366
Steareth-2 B 1.097
Distearyldimonium chloride B 0.950
N-乙酰基-半胱氨酸 C 2.00
氧化锌 C 0.40
肌醇六磷酸 C 5.00
鲸蜡基甜菜碱 C 1.50
对羟苯甲酸甲酯 C 0.10
EDTA二钠 C 0.05
1M NaOH C 调节pH
灭菌水 C 20.999
DCO22-1401 D 0.750
(cyclo methicone/dimethiconol 50/50
混合)
聚乙烯低密度泡沫 D 2.00
苄基醇 D 0.50
香料 D 0.2A,B,C和D相用混合机分开掺和。A相和B相混合物在搅拌下被分开加热至65-75℃然后混合并用混合机掺混,然后均化。A相加B相混合物被冷却至45-50℃。C相混合物被调至pH6。C相和D相混合物然后被加到A相加B相混合物并用混合机掺混。最后的pH被调至6.5。
由于本发明的特定方案已被描述,本专业熟练的技术人员将明白,本发明的各种改变和修改可以不脱离本发明的精神范围进行。在所附权利要求中,所有在本发明范围内的修改倾向于被覆盖。
Claims (7)
1.一种用于哺乳动物皮肤去屑的局部组合物,其特征在于其包含:
a)基本由如下组成的去屑活性物:
其中R1是具有9至22个碳原子的未取代的,饱和或不饱和的,直链或支链烷基;m是1至3的整数;n是0或1;R2和R3独立地为具有1至3个碳原子,未取代或用羟基单取代的烷基;R4是具有1至5个碳原子,饱和或不饱和的,直链或支链的,未取代或被羟基单取代的烷基;而X选自由CO2,SO3和SO4组成的一组;或前述化合物的美容和/或药学上可接受的盐;
优选地其中R2和R3选自由CH3,CH2CH2OH和CH2CH2CH2OH组成的一组;X是CO2或SO3;而m是2或3;
更优选地其中X是CO2时R4具有1至3个碳原子;而当X是SO3时R4具有2至4个碳原子;
还更优选地其中R1具有11至18个碳原子;R2和R3是CH3;当X是CO2时R4具有1个碳原子;当X为SO3时R4具有3个碳原子;
最优选地其中R1具有11至18个碳原子;R2和R3是CH3;当X是CO2时R4具有1个碳原子;当X是SO3时R4具有3个碳原子;m是3而n是1;和
(ii)安全和有效量的巯基化合物,选自由N-乙酰基-L-半胱氨酸,谷胱甘肽,甲硫氨酸,二硫苏糖醇,二硫赤藓糖醇,高胱氨酸,和任何前述化合物的美容-和/或药学上可接受的盐;
优选地为N-乙酰基-L-半胱氨酸,谷胱甘肽,甲硫氨酸,和任何前述化合物的美容和/或药学上可接受的盐;
更优选地为N-乙酰基-L-半胱氨酸或其美容和/或药学上可接受的盐;和
b)美容和/或药学上可接受的局部用载体。
2.权利要求1的组合物,其中两性离子表面活性剂是山萮基甜菜碱,可可酰氨基丙基甜菜碱,鲸蜡基丙基羟基sultaine(cetyl propyl hydroxysultaine),硬脂基甜菜碱或鲸蜡基甜菜碱,优选地为硬脂基甜菜碱或鲸蜡基甜菜碱。
3.权利要求1或2的组合物,其中组合物进一步包含0.1%至10%的水杨酸。
4.实现哺乳动物皮肤去屑的方法,特征在于其包含对需要这类治疗的哺乳动物局部施用包含如下组分的组合物;
a)安全和有效量的巯基化合物,选自由N-乙酰基-L-半胱氨酸,谷胱甘肽,甲硫氨酸,二硫苏糖醇,二硫赤藓糖醇,高胱氨酸,和上述化合物的美容和/或药学上可接受的盐;
优选地为N-乙酰基-L-半胱氨酸,谷胱甘肽,甲硫氨酸,和任何上述化合物的美容和/或药学上可接受的盐;
更优选地为N-乙酰基-L-半胱氨酸或其美容和/或药学上可接受的盐;
其中R1是具有9至22个碳原子,未取代的,饱和或不饱和的,直链或支链烷基;m是1至3的整数;n是0或1;R2和R3独立地为具有1至3个碳原子,未取代或被羟基单取代的烷基;R4是具有1至5个碳原子,饱和或不饱和的,未取代或被羟基单取代的直链或支链烷基;而X选自由CO2,SO3和SO4组成的一组;或上述化合物的美容和/或药学上可接受的盐;
优选地其中R2和R3是选自由CH3,CH2CH2OH和CH2CH2CH2OH组成的一组;X是CO2或SO3;而m为2或3;
更优选地其中当X为CO2时R4具有1至3个碳原子,而当X为SO3时R2具有2至4个碳原子;
还更优选地其中R1具有11至18个碳原子;R2和R3是CH3;当X是CO2时R4具有1个碳原子;当X是SO3时,R4具有3个碳原子;
最优选地其中R1具有11至18个碳原子;R2和R3是CH3;当X为CO2时R4具有1个碳原子;当X是SO3时R4具有3个碳原子;m是3而n为1;和
c)美容和/或药学上可接受的局部用载体;所用巯基化合物的量为0.004mg/cm2皮肤至0.1mg/cm2皮肤,更优选地为0.02mg/cm2皮肤至0.06mg/cm2皮肤;
所用两性离子表面活性剂优选地为0.004mg/cm2皮肤至0.1mg/cm2皮肤,更优地为0.02mg/cm2皮肤至0.06mg/cm2皮肤。
5.治疗哺乳动物皮肤上粉刺的方法,其特征在于包含对患有粉刺的哺乳动物局部施用包含如下组分组合物:
a)安全和有效量的巯基化合物,选自由N-乙酰基-L-半胱氨酸,谷胱甘肽,甲硫氨酸,二硫苏糖醇,二硫赤藓糖醇,高胱氨酸,和任何上述化合物的美容和/或药学上可接受的盐;
优地为N-乙酰基-L-半胱氨酸,谷胱甘肽,甲硫氨酸,和任何上述化合物的美容和/或药学上可接受的盐;
更优选地为N-乙酰基-L-半胱氨酸或其美容和/或药学上可接受的盐;
b)安全和有效量的具有如下结构的两性离子表面活性剂:
其中R1是具有9至22个碳原子,未取代的,饱和或不饱和的,直链或支链烷基;m是1至3的整数;n是0或1;R2和R3独立地为具有1至3个碳原子,未取代或被羟基单取代的烷基;R4是具有1至5个碳原子,饱和或不饱和的,未取代或被羟基单取代的直链或支链烷基;而X选自由CO2,SO3和SO4组成的一组;或上述化合物的美容和/或药学上可接受的盐;
优选地其中R2和R3选自由CH3,CH2CH2OH和CH2CH2CH2OH组成的一组;X是CO2或SO3;而m为2或3;
更优选地其中当X是CO2时R4具有1至3个碳原子;而当X是SO3时R4具有2至4个碳原子;
还更优选地其中R1具有11至18个碳原子;R2和R3是CH3;当X是CO2时R4具有1个碳原子;当X是SO3时,R4具有3个碳原子;
最优选地其中R1具有11至18个碳原子;R2和R3是CH3;当X是CO2时R4具有1个碳原子;当X是SO3时,R4具有3个碳原子;m是3,而n为1;和
c)美容和/或药学上可接受的局部用载体;所用巯基化合物的量优选地为0.004mg/cm2皮肤至0.1mg/cm2皮肤,更优地为0.02mg/cm2皮肤至0.06mg/cm2皮肤;
所用两性离子表面活性剂优选地为0.004mg/cm2皮肤至0.1mg/cm2皮肤,更优地为0.02mg/cm2皮肤至0.06mg/cm2皮肤。
6.权利要求4或5的方法,其中两性离子表面活性剂是山萮基甜菜碱,可可酰胺基丙基甜菜碱,鲸蜡基丙基羟基sultaine(cetyl propylhydroxy sultaine),硬脂基甜菜碱或鲸蜡基甜菜碱,优选地为硬脂基甜菜碱或鲸蜡基甜菜碱。
7.权利要求4,5或6的方法,其中组合物进一步包含0.1%至10%水杨酸。
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US26974594A | 1994-07-01 | 1994-07-01 | |
US08/269,745 | 1994-07-01 |
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CN1107495C CN1107495C (zh) | 2003-05-07 |
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EP (1) | EP0768866B1 (zh) |
JP (1) | JPH10505326A (zh) |
CN (1) | CN1107495C (zh) |
AT (1) | ATE215810T1 (zh) |
AU (1) | AU703079B2 (zh) |
CA (1) | CA2194158C (zh) |
CZ (1) | CZ385896A3 (zh) |
DE (1) | DE69526350T2 (zh) |
ES (1) | ES2174951T3 (zh) |
MX (1) | MX9700053A (zh) |
TW (1) | TW402500B (zh) |
WO (1) | WO1996001101A1 (zh) |
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CN110585046A (zh) * | 2019-10-12 | 2019-12-20 | 曹志军 | 一种去屑止屑防脱发增发组份及产品 |
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US5821237A (en) * | 1995-06-07 | 1998-10-13 | The Procter & Gamble Company | Compositions for visually improving skin |
TW508247B (en) * | 1997-03-31 | 2002-11-01 | Shiseido Co Ltd | Cosmetic or dermatological topical composition |
BR9908870A (pt) * | 1998-03-16 | 2000-11-21 | Procter & Gamble | Processos para regularizarem a aparência da pele |
WO2000044341A1 (fr) * | 1999-01-28 | 2000-08-03 | Shiseido Company, Ltd. | Compositions destinees a un usage externe |
US20040235950A1 (en) * | 1999-05-20 | 2004-11-25 | Voorhees John J. | Compositions and methods for use against acne-induced inflammation and dermal matrix-degrading enzymes |
DE19950019A1 (de) * | 1999-10-16 | 2001-04-19 | Henkel Kgaa | Tensidhaltige Reinigungsmittel mit Enzym-Inhibitoren |
US20050003024A1 (en) | 2003-03-04 | 2005-01-06 | The Procter & Gamble Company | Regulation of mammalian hair growth |
US20040175347A1 (en) | 2003-03-04 | 2004-09-09 | The Procter & Gamble Company | Regulation of mammalian keratinous tissue using hexamidine compositions |
US20050090551A1 (en) * | 2003-10-27 | 2005-04-28 | Board Of Trustees Of Southern Illinois University | Therapeutic use of methionine for the treatment or prevention of mucositis |
ES2747926T3 (es) | 2004-09-27 | 2020-03-12 | Special Water Patents B V | Métodos y composiciones para el tratamiento de agua |
EP1948236B1 (en) | 2005-09-27 | 2021-03-03 | Special Water Patents B.V. | Methods and compositions for treatment of skin |
DE112007001469T5 (de) * | 2006-06-23 | 2009-06-04 | Ajinomoto Co., Inc. | Collagensynthese-Promotor, der Zink als aktiven Bestandteil enthält |
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US4800197A (en) * | 1987-07-17 | 1989-01-24 | Richardson-Vicks Inc. | Anti-acne composition |
US5296500A (en) * | 1991-08-30 | 1994-03-22 | The Procter & Gamble Company | Use of N-acetyl-cysteine and derivatives for regulating skin wrinkles and/or skin atrophy |
GB9223034D0 (en) * | 1992-11-03 | 1992-12-16 | Surtech Int Ltd | Method and composition for prevention and/or treatment of dandruff and seborrhoeic dermatitis |
NZ260848A (en) * | 1993-07-09 | 1996-08-27 | Colgate Palmolive Co | High foaming liquid detergent comprising as nonionic surfactant an alkyl or fatty acid sorbitan ether with an ethylene oxide condensate, or an alkylphenolether of an ethylene oxide/propylene oxide condensate, a betaine and an ethoxylated alkyl ether sulphate |
DK0730441T3 (da) * | 1993-11-12 | 2002-03-18 | Procter & Gamble | Deskvamationspræparater, der indeholder salicylsyre og zwitterioniske forbindelser |
-
1995
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- 1995-06-29 DE DE69526350T patent/DE69526350T2/de not_active Expired - Fee Related
- 1995-06-29 CZ CZ963858A patent/CZ385896A3/cs unknown
- 1995-06-29 AU AU29514/95A patent/AU703079B2/en not_active Ceased
- 1995-06-29 EP EP95925348A patent/EP0768866B1/en not_active Expired - Lifetime
- 1995-06-29 CA CA002194158A patent/CA2194158C/en not_active Expired - Fee Related
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MX9700053A (es) | 1997-04-30 |
CN1107495C (zh) | 2003-05-07 |
AU2951495A (en) | 1996-01-25 |
EP0768866B1 (en) | 2002-04-10 |
ATE215810T1 (de) | 2002-04-15 |
AU703079B2 (en) | 1999-03-11 |
TW402500B (en) | 2000-08-21 |
JPH10505326A (ja) | 1998-05-26 |
DE69526350D1 (de) | 2002-05-16 |
CZ385896A3 (en) | 1997-08-13 |
WO1996001101A1 (en) | 1996-01-18 |
CA2194158A1 (en) | 1996-01-18 |
DE69526350T2 (de) | 2003-03-13 |
EP0768866A1 (en) | 1997-04-23 |
CA2194158C (en) | 2000-08-22 |
ES2174951T3 (es) | 2002-11-16 |
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