CN107846880A - 抗微生物组合物 - Google Patents
抗微生物组合物 Download PDFInfo
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- CN107846880A CN107846880A CN201680041377.9A CN201680041377A CN107846880A CN 107846880 A CN107846880 A CN 107846880A CN 201680041377 A CN201680041377 A CN 201680041377A CN 107846880 A CN107846880 A CN 107846880A
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Abstract
描述了具有成分的协同组合的抗微生物组合物。还描述了具有改善的防腐性质的含有所述抗微生物组合物的化妆品组合物。所述化妆品组合物在被局部施加后处理皮肤以清洁、保湿并减少老化和光损伤的影响以及在处理其它皮肤状况方面是有效的。
Description
技术领域
本发明涉及含有成分的协同共混物的抗微生物组合物,并且还涉及含有所述抗微生物组合物的化妆品组合物。
背景技术
由于皮肤病症、环境滥用(风、空气调节、集中供热)或由于正常老化过程(随时间老化),皮肤会经受衰退,当暴露于阳光(光老化)时可加速皮肤衰退。近年来,对用于改善皮肤的外观和状况的化妆品组合物和化妆方法的需求已经大大增长。需要与此类化妆品组合物相容的有效的抗微生物组合物。
除了其皮肤益处之外,消费者还常常寻求来自化妆产品的其它益处。“敏感皮肤”的概念也提高了消费者对具有安全且有效的抗微生物化合物的化妆产品的需求。
用于改善皮肤的状况和外观的化妆品和组合物包含许多不同的抗微生物体系。
于1976年8月24日授予Buckman等的美国专利第3,976,495号公开了羟基苯乙酮衍生物作为杀真菌剂的用途。于2011年11月3日公布的授予Winn的美国专利申请第2011/0268676号公开了异羟肟酸作为用于化妆品组合物的防腐剂的用途。均于2015年4月30日公布授予Thomas Ruolph等的美国申请公布US 2015/0118172和US 2015/0118165及2014年11月13日公布的授予Thomas Ruolph等的美国申请公布US 2014/0335029公开了特定的环己醇和环己基烷醇作为抗微生物试剂的用途。
然而,仍然持续需要用于化妆品组合物的安全且有效的抗微生物组合物,用于局部施用于皮肤以带来各种益处,包括但不限于清洁、保湿、处理/延迟老化和光损伤皮肤的可见征象,如皱纹、纹线、松垂、色素沉着过度、老年斑和其它皮肤状况。
我们现已惊讶地发现含有以下组分的组合的抗微生物组合物:i.苯基烷醇或苯基烷氧基化合物或两者;ii.具有(RCONHOH)(其中R是直链烷基)结构的异羟肟酸和其共混物;iii.一种或多种羟基苯乙酮,以及IV.一种或多种选自以下的环烷基化合物:环己醇、环烷醇、金刚烷醇、金刚烷烷醇、氨基金刚烷、金刚烷铵、降冰片烷醇、降冰片烷烷醇、氨基降冰片烷、降冰片烷铵其共混物,所述组合提供的协同效应(efficacy)显著大于单个化合物或不同组合在以下方面所赋予的协同效应:防止众多革兰氏阴性细菌、革兰氏阳性细菌、酵母菌和霉菌微生物的生长,包括但不限于洋葱伯克霍尔德氏菌(Burkholderia cepacia)、铜绿假单胞菌(Pseudomonas aeruginosa)、恶臭假单胞菌(Pseudomonas putida)、日沟维肠杆菌(Enterobacter gergoviae)、克雷伯氏菌属种(Klebsiella species)、金黄色葡萄球菌(Staphylococcus aureus)、白色念珠菌(Candida albicans)、巴西曲霉(Aspergillusbrasiliensis)及其它,并且其中本发明的抗微生物组合物额外地与用于清洁或处理许多皮肤状况的化妆品皮肤配制物相容。
发明内容
在第一方面,本发明涉及抗微生物组合物,其包含但不限于:
a.一种或多种苯基烷醇或苯基烷氧基化物(phenyl alkoxyl)或其共混物;
b.一种或多种具有其中R为直链烷基的结构(RCONHOH)的异羟肟酸或其共混物;
c.一种或多种羟基苯乙酮或其共混物,和
d.一种或多种选自以下组中的环烷基化合物:环己醇、环己基烷醇、金刚烷醇、金刚烷烷醇、氨基金刚烷、金刚烷铵、降冰片烷醇、降冰片烷烷醇、氨基降冰片烷、降冰片烷铵或其共混物。
在本发明的另一方面中是化妆品组合物,其包含但不限于与上述抗微生物组合物配制的化妆品上可接受的基料。
在本发明的又一方面是化妆品组合物防止至少一种革兰氏阴性细菌、革兰氏阳性细菌、酵母菌和霉菌微生物生长或其任意组合的方法,其包括但不限于以下步骤:
a.制备化妆品上可接受的基料;和
b.共混所述基料与上述抗微生物组合物直至均质。
在本发明的另一方面是用化妆品组合物处理皮肤的方法,其包括但不限于向所述皮肤施用上述化妆品组合物的步骤。
在考虑以下的详细描述和实施例后,本发明的所有其它方面将更容易变得清楚明了。
如本文所用的,皮肤意在包括面部、颈部、胸部、背部、臂部(包括腋下)、手、腿、臀部和头皮上的皮肤。如本文所用的,活性物意在包括改善皮肤特性和/或有益于皮肤的组分,其中所述组分在化妆品组合物中可以是并且优选是活性物,最优选是霜剂、乳剂、香脂、除臭剂或凝胶。
如本文所用的,包含意在包括基本上由……组成和由……组成。因此,为了避免疑问,本发明的化妆品组合物和方法可基本上由所要求保护的组分组成,或由所要求保护的组分组成。如果例如没有明确提及的话,则本文中所确定的所有范围均意在包括其中所包含的所有范围。
除了在操作实施例和比较实施例中或者另有明确指示的情况下以外,说明书中指示的材料的量或比率或条件或反应、材料的物理性质和/或用途的所有数字均应理解为由词语“约”修饰。
当在说明书中使用时,术语“包含”意在包括存在所述特征、整数、步骤、组分,但不排除存在或增加一个或多个特征、整数、步骤、组分或它们的组。
除非另有说明,否则说明书和实施例中的所有百分比均意在以参照组合物的重量计。
具体实施方式
在第一方面,本发明涉及抗微生物组合物,其包含但不限于:
a.一种或多种苯基烷醇或苯基烷氧基化物或其共混物;
b.一种或多种具有其中R为直链烷基的结构(RCONHOH)的异羟肟酸或其共混物;
c.一种或多种羟基苯乙酮或其共混物,任选地其中所述羟基苯乙酮中的一种或多种被一个、两个、三个或四个另外的羟基独立地环取代;和
d.一种或多种选自由以下组成的组的环烷基化合物:环己醇、环己基烷醇、金刚烷醇、金刚烷烷醇、氨基金刚烷、金刚烷铵、降冰片烷醇、降冰片烷烷醇、氨基降冰片烷、降冰片烷铵或其共混物。
优选地,所述抗微生物组合物含有:
a.至少50%、优选60%、更优选70%、甚至更优选80%、甚至更优选90%、甚至更优选95%、甚至更优选99%或最优选100%,优选50-100%、更优选60-99%、更优选70-95%、甚至更优选80-100%存在的总苯基烷醇和苯基烷氧基化物选自苯氧基乙醇、苄醇、苯乙醇(phenethyl alcohol)或其共混物;
b.至少50%、优选60%、更优选70%、甚至更优选80%、甚至更优选90%、甚至更优选95%、甚至更优选99%或最优选100%,优选50-100%、更优选60-99%、更优选70-95%、甚至更优选80-100%存在的总异羟肟酸选自C1至C12直链烷基、优选C6至C12直链烷基,更优选地包括辛基异羟肟酸(octanohydroxamic acid)、六碳异羟肟酸(caprohydroxamicacid)、月桂基异羟肟酸(laurohydroxamic acid)、己基异羟肟酸(hexanohydroxamicacid)或其共混物;
c.至少50%、优选60%、更优选70%、甚至更优选80%、甚至更优选90%、甚至更优选95%、甚至更优选99%或最优选100%,优选50-100%、更优选60-99%、更优选70-95%、甚至更优选80-100%存在的总羟基苯乙酮选自4-羟基苯乙酮、3-羟基苯乙酮、2-羟基苯乙酮或其共混物;
d.至少50%、优选60%、更优选70%、甚至更优选80%、甚至更优选90%、甚至更优选95%、甚至更优选99%或最优选100%,优选50-100%、更优选60-99%、更优选70-95%、甚至更优选80-100%存在的总环烷基化合物具有以下I、II、III的结构或其任意组合:
I.
II.
III.
其中
R1=-OH、-OCH3、-OCH2CH3、-NH2、NH(CH3)、-N(CH3)2、-N+(CH3)3X-(X=F、Cl、Br、I)
R2=-COOCH2CH3、-H
R3=-H、-OH、-OCH3
R4=C6H11-CH-OH;C6H11-CH-OCH3-;C6H5-CH-OCH2CH3;4C6H11-CH-OCH2CH3。
有利地,所述抗微生物组合物含有:
a.0.1-25重量%的总量浓度的苯基烷醇或苯基烷氧基烷醇或两者;
b.约0.1-25重量%的总量浓度的异羟肟酸;
c.约0.1-25重量%的总量浓度的羟基苯乙酮;
d.约0.1-25重量%的总量浓度的环烷基化合物;和
e.浓度为约99.4-0重量%的相容性载体。
优选地,环烷基化合物选自化合物(1)至(14)或其共混物:
优选地,环烷基化合物包括化合物(1)、化合物(3)或其共混物;更优选地,化合物(1)与化合物(3)的重量比在约0.4至2的范围内;最优选地,化合物(1)与化合物(3)的重量比具有约1的最大值。
在本发明的另一方面中是化妆品组合物,其包含但不限于:
a.化妆品上可接受的基料;和
b.上述抗微生物组合物。
优选地,所述抗微生物组合物以在第21天时使用改进的挑战测试(challengetest)有效地至少抑制99%的至少一种活微生物再生长的量存在于所述化妆品组合物中,其中所述微生物选自洋葱伯克霍尔德氏菌(B.cepacia)、铜绿假单胞菌(P.aeruginosa)、恶臭假单胞菌(P.putida)、金黄色葡萄球菌(S.aureus)、白色念珠菌(C.albicans)和巴西曲霉(A.brasiliensis)或其任意组合。
更优选地,所述化妆品组合物包含:
a.基于所述化妆品组合物,总量浓度为约0.2-1.0重量%,优选至少约0.4重量%且最大约0.7重量%的苯基烷醇、苯基烷氧基烷醇或其共混物;
b.基于所述化妆品组合物,总量浓度为约0.1-1.2重量%,优选至少约0.35重量%且最大约0.7重量%的异羟肟酸;
c.基于所述化妆品组合物,总量浓度为约0.1-1.0重量%,优选至少约0.25重量%且最大约0.5重量%的羟基苯乙酮。
d.基于所述化妆品组合物,总量浓度为约0.5-1.0重量%的环烷基化合物。
有利地,异噻唑啉酮抗微生物化合物存在的总量最大量为基于所述化妆品组合物重量的0.15重量%。
在本发明的又一方面是在化妆品组合物中防止革兰氏阴性细菌、革兰氏阳性细菌、酵母菌和霉菌微生物的至少一种生长或其任意组合的方法,其包括但不限于以下步骤:
a.制备化妆品上可接受的基料;和
b.共混所述基料与上述抗微生物组合物,直至均质。
在本发明的另一方面是用化妆品组合物处理皮肤的方法,其包括但不限于向所述皮肤施用上述化妆品组合物的步骤。
i.苯基烷醇和苯基烷氧基烷醇:
本发明的抗微生物组合物优选包含一种或多种苯基烷醇、苯基烷氧基烷醇或其共混物。可用的化合物包括苯氧基乙醇、苄醇、苯乙醇等。
ii.异羟肟酸
本发明的抗微生物组合物优选包含一种或多种异羟肟酸,即(RCONHOH),其中R为直链烷基,优选其中R为C1至C12、更优选C6至C12的直链烷基。有用的化合物包括六碳异羟肟酸(caprohydroxamic acid,caprylohydroxamic acid)、辛基异羟肟酸、月桂基异羟肟酸、己基异羟肟酸或其共混物等。
iii.羟基苯乙酮
本发明的抗微生物组合物优选包含一种或多种羟基苯乙酮或其共混物,其任选被一个、两个、三个或四个另外的羟基环取代。有用的化合物包括4-羟基苯乙酮、3-羟基苯乙酮、2-羟基苯乙酮或其共混物等。
iv.环烷基化合物:
本发明的抗微生物组合物优选包含选自以下的一种或多种的环烷基化合物:环己醇、环己基烷醇、金刚烷醇、金刚烷烷醇、氨基金刚烷、金刚烷铵、降冰片烷醇、降冰片烷烷醇、氨基降冰片烷或降冰片烷铵或其共混物;优选根据结构I、II和III的环烷基化合物。
其中
R1=-OH、-OCH3、-OCH2CH3、-NH2、NHCH3、-N(CH3)3、-N+(CH3)3X-(X=F、Cl、Br或I)
R2=-COOCH2CH3、-H
R3=-H、-OH、-OCH3
R4=C6H11-CH-OH;C6H11-CH-OCH3-;C6H5-CH-OCH2CH3;4C6H11-CH-OCH2CH3
可用的环烷基化合物包括以下:
抗微生物组合物载体:
任选地,载体可与本发明的抗微生物组合物一起使用。载体优选与抗微生物组合物的成分相容,使得其不会降低所述抗微生物组合物的效能(efficacy)或引起任何分解或有害的化学变化,或不会促进或引起本发明的组分与所述载体或彼此反应或相互作用而损害抗微生物组合物的抗微生物效能,或不会负面地影响所述载体与之配制的化妆品组合物的稳定性、效能、安全性或质量。载体可以是单一化合物,或以有效溶解或分散抗微生物组合物的成分的量使用的化合物的共混物。相容在本文中定义为与抗微生物组合物的成分形成溶液或分散体的化合物或化合物的共混物,其中所述抗微生物组合物的效能在45℃和1ATM压力下在黑暗中储存60天后保持为大于其初始效能的99%、98%、95%、90%、80%、70%或60%。初始效能是在第21天使用相同载体在25℃和1ATM下制备本发明组合物后1小时内,使用选自以下的最有耐受性的生物体,利用下文所述的改进的挑战测试所测量的其效能:洋葱伯克霍尔德氏菌、铜绿假单胞菌、恶臭假单胞菌、洋葱伯克霍尔德氏菌054、金黄色葡萄球菌、白色念珠菌和巴西曲霉;将结果与对在45℃和1ATM压力下在黑暗中储存60天的相同抗微生物组合物的等分试样所进行的相同的改进的挑战测试进行比较。
载体可包括下文所述的一种或多种化妆品上可接受的载体。除了此类化妆品上可接受的载体之外或代替此类化妆品上可接受的载体,所述载体可包括以下化合物中的一种或多种:合成或天然来源的化合物,包括但不限于一种或多种直链或环状脂族烃、烯基烃、炔基烃和芳族烃;杂环化合物、醛、酯、酮、醚或羧酸;上述化合物任选地经一个或多个官能团取代,其中所述官能团可含有氧、氮、硫、磷、卤素或其任意组合。
抗微生物有效性:
预期本发明的抗微生物组合物对以下微生物中的至少一种或多种有效:革兰氏阴性微生物、革兰氏阳性微生物、酵母菌和霉菌。优选其对它们中的至少两种、三种或全部有效。本发明的组合物显示对以下微生物有效:
革兰氏阴性:洋葱伯克霍尔德氏菌、铜绿假单胞菌和恶臭假单胞菌;革兰氏阳性:金黄色葡萄球菌、酵母菌、白色念珠菌和霉菌:巴西曲霉;使用下文所描述的改进的挑战测试。
化妆品组合物:
适用于本发明中的活性物意在包括但不限于不透明剂、着色剂、亮肤剂、保湿剂、植物提取物、抗炎剂、表面活性剂、减皱纹剂、其混合物等。
除了本文所述的本发明抗微生物组合物之外,本发明的化妆品组合物通常还包含化妆品上可接受的载体组分。这些还可包含抗微生物载体。水是最优选的载体。水的量可优选基于全部化妆品组合物总重量的约1-约98重量%、更优选约5-约90重量%且最优选约35-约80重量%且最佳约40-约80重量%的范围,并且包括其中所含的所有范围。
适用于本发明中的化妆品上可接受的载体可包括矿物油、甘油二酯油和甘油三酯油、硅油、合成酯或天然酯以及醇。这些材料的总量可在以所述化妆品组合物的重量计约0.1-约50%且优选约0.1-约30%并且最优选约1-约20%的范围,包括其中所包含的所有范围。
硅油分为挥发性和非挥发性的种类。如本文所用的术语"挥发性"是指在环境温度(例如25℃)下具有可测量的蒸气压的那些材料。挥发性硅油优选选自含有约3至约9个、优选约4至约5个硅原子的环状或直链聚二甲基硅氧烷。
线性挥发性有机硅材料通常具有25℃下小于约5厘沲(0.5×10-5m2/s)的粘度,而环状材料通常具有小于约10厘沲(1.0×10-5m2/s)的粘度。
可用作化妆品组合物中的载体材料的非挥发性硅油包括聚烷基硅氧烷、聚烷基芳基硅氧烷和聚醚硅氧烷共聚物。可用于本文中的基本上非挥发性的聚烷基硅氧烷包括例如在25℃下粘度为约5至约100,000厘沲(0.5×10-5至10,000×10-5m2/s)的聚二甲基硅氧烷(如Dimethicone二甲硅油)。适合使用的硅油(尤其是二甲硅油35至75厘沲(3.5×10-5至7.5×10-5m2/s))经常可从Dow Corning商购获得,并且是优选的。
尤其合适的酯是:
(1)具有10至20个碳原子的脂肪酸的烯基酯或烷基酯,如棕榈酸异丙酯、异硬脂酸异丙酯、异壬酸异壬酯、肉豆蔻酸油烯基酯、肉豆蔻酸异丙酯、硬脂酸油烯基酯和油酸油烯基酯;
(2)醚酯,如乙氧基化脂肪醇的脂肪酸酯;
(3)多元醇酯,如乙二醇单脂肪酸酯和乙二醇二脂肪酸酯、二乙二醇单脂肪酸酯和二乙二醇二脂肪酸酯、聚乙二醇(200-6000)单脂肪酸酯和聚乙二醇(200-6000)二脂肪酸酯、丙二醇单脂肪酸酯和丙二醇二脂肪酸酯、聚丙二醇2000单油酸酯、聚丙二醇2000单硬脂酸酯、乙氧基化丙二醇单硬脂酸酯、单脂肪酸甘油酯和二脂肪酸甘油酯、聚甘油多脂肪酯、乙氧基化单硬脂酸甘油酯、1,3-丁二醇单硬脂酸酯、1,3-丁二醇二硬脂酸酯、聚氧乙烯多元醇脂肪酸酯、山梨糖醇酐脂肪酸酯和聚氧乙烯山梨糖醇酐脂肪酸酯;
(4)蜡酯,如蜂蜡、鲸蜡、肉豆蔻酸肉豆蔻基酯、硬脂酸硬脂基酯;和
(5)固醇酯,其中大豆固醇脂肪酸酯和胆固醇脂肪酸酯是其实例。
乳化剂优选存在于本发明的化妆品组合物中。乳化剂的总浓度可在以所述化妆品组合物的重量计约0.1-约40%且优选约1-约20%并且最优选约1-约7%的范围,包括其中所包含的所有范围。
乳化剂可选自由阴离子型活性物、非离子型活性物、阳离子型活性物和两性活性物组成的组。特别优选的非离子型活性物是具有以下的那些:C10-C20脂肪醇疏水物或脂肪酸疏水物,其与每摩尔疏水物约2至约100摩尔氧化乙烯或氧化丙烯缩合;与2至20摩尔氧化烯缩合的C2-C10烷基酚;乙二醇单脂肪酸酯和乙二醇二脂肪酸酯;脂肪酸甘油单酯;山梨糖醇酐单C8-C20脂肪酸和山梨糖醇酐二C8-C20脂肪酸;和聚氧乙烯山梨糖醇酐以及其组合。烷基聚糖苷和糖脂肪酰胺(例如甲基葡糖酰胺)也是合适的非离子型乳化剂。
优选的阴离子型乳化剂包括烷基醚硫酸盐和烷基醚磺酸盐、烷基硫酸盐和烷基磺酸盐、烷基苯磺酸盐、烷基磺基琥珀酸盐和二烷基磺基琥珀酸盐、C8-C20酰基羟乙基磺酸盐、C8-C20烷基醚磷酸盐、烷基醚羧酸盐和其组合。
可使用的阳离子型乳化剂包括例如棕榈酰胺基丙基三甲基氯化铵(palmitamidopropyltrimonium chloride)、二硬脂基二甲基氯化铵和其混合物。有用的两性乳化剂包括椰油酰胺基丙基甜菜碱、C12-C20三烷基甜菜碱、月桂酰两性基乙酸钠(sodiumlauroamphoacetate)和月桂酰双两性基乙酸钠或其混合物。
其它通常优选的乳化剂包括硬脂酸甘油酯、硬脂酸二醇酯、硬脂酰胺AMP、PEG-100硬脂酸酯、鲸蜡醇以及乳化/增稠添加剂,如丙烯酸羟乙酯/丙烯酰二甲基牛磺酸钠共聚物/角鲨烷,和其混合物。
还可使用通常分类为基于植物的液体的乳液稳定剂。优选的稳定剂以名称OilwaxLC出售并由Lotioncrafter市售。
除了本发明的抗微生物组合物之外,还可满意地将另外的抗微生物化合物并入本发明的化妆品组合物中,以防止潜在有害微生物的生长。然而,防腐剂是具有由监管机构限定的上限的调节成分。另外,许多防腐剂是皮肤敏化剂,优选使用最低浓度的防腐剂,防止可能破坏产品并构成消费者安全风险的潜在有害微生物。用于本发明的化妆品组合物中的适合的传统抗微生物化合物是对羟基苯甲酸的烷基酯。最近开始使用的其它抗微生物化合物包括异噻唑啉酮、DMDM乙内酰脲衍生物、丙酸盐和各种季铵化合物。化妆品药剂师熟悉适当的抗微生物化合物,并且常规地选择它们以满足防腐挑战测试(preservativechallenge test),提供产品效能和稳定性。特别优选的抗微生物化合物是丁基氨基甲酸碘代丙炔基酯、苯氧基乙醇、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、咪唑烷基脲(imidazolidinyl urea)、脱氢乙酸钠和苄醇。应当考虑在化妆品组合物中的用途以及抗微生物化合物和乳液中其它成分之间可能的不相容性来选择所述抗微生物化合物。另外的抗微生物化合物优选以在以化妆品组合物的重量计约0.01-约1%范围的量采用,包括其中所包含的所有范围。最优选地,异噻唑啉酮抗微生物化合物以0.02%、0.06%或0.15%的最高水平存在,并且优选不存在于本发明的化妆品组合物中。
增稠剂可任选地包含在本发明的化妆品组合物中。特别有用的是多糖。实例包括淀粉、天然/合成胶和纤维素类。淀粉的代表是化学改性淀粉,如羟丙基淀粉磷酸钠和淀粉辛烯基琥珀酸铝。经常优选木薯淀粉。合适的胶包括黄原胶、菌核、果胶、刺梧桐胶、阿拉伯胶、琼脂、瓜尔胶、角叉菜胶、藻酸盐和其组合。合适的纤维素类包括羟丙基纤维素、羟丙基甲基纤维素、乙基纤维素和羧基甲基纤维素钠。合成聚合物是又一类别的有效增稠剂。该分类包括交联的聚丙烯酸酯如卡波姆、聚丙烯酰胺如305和牛磺酸盐共聚物如Simulgel 和 AVC,所述共聚物由各自的INCI命名法鉴别为丙烯酸钠/丙烯酰基二甲基牛磺酸钠和丙烯酰基二甲基牛磺酸盐/乙烯基吡咯烷酮共聚物。另一优选的适于增稠的合成聚合物是基于丙烯酸酯的聚合物,其可由Seppic商购并以名称SimulgelINS100出售。
当使用时,增稠剂的量可在以化妆品组合物的重量计约0.001-约5%且优选约0.1-约3%且最优选约0.1-约1.5%的范围,包括其中所包含的所有范围。
常规的湿润剂可用于本发明中。这些通常是多元醇型物质。典型的多元醇包括甘油(即glycerol、glycerine或glycerin)、丙二醇、二丙二醇、聚丙二醇、聚乙二醇、山梨醇、羟丙基山梨醇、己二醇、1,3-丁二醇、异戊二醇、1,2,6-己三醇、乙氧基化甘油、丙氧基化甘油和其混合物。最优选的是甘油、丙二醇或其混合物。所用的湿润剂的量可在以化妆品组合物的重量计0.5-25%且优选1-20%的范围。
芳香剂、着色剂、固定剂(fixative)和研磨剂可任选地包含在本发明的化妆品组合物中。这些物质中的每一种均可在约0.05-约5重量%、优选0.1-3重量%的范围。
就适用于化妆品组合物中的活性物而言,其可包括不透明剂如TiO2和ZnO以及着色剂如氧化铁红、氧化铁黄和氧化铁黑。此类不透明剂和着色剂通常具有50至1200nm且优选50至350nm的粒径。
为了增强皮肤保湿,分类为阳离子铵化合物的活性物可任选地用于本发明的化妆品组合物中。此类化合物包括羟丙基三(C1-C3烷基)铵单取代的糖的盐、羟丙基三(C1-C3烷基)铵单取代的多元醇的盐、二羟丙基三(C1-C3烷基)铵盐、二羟丙基二(C1-C3烷基)单(羟乙基)铵盐、瓜尔羟丙基三甲基铵盐、2,3-二羟丙基三(C1-C3烷基或羟烷基)铵盐或其混合物。在最优选的实施方案中并且当期望时,用于本发明中的阳离子铵化合物是季铵化合物1,2-二羟丙基三甲基氯化铵。如果使用,此类化合物通常占化妆品组合物的约0.01-约30重量%且优选约0.1-约15重量%。
当使用阳离子铵化合物时,与其使用的优选的另外的活性物是保湿剂如取代的脲,如羟甲基脲、羟乙基脲、羟丙基脲;双(羟甲基)脲;双(羟乙基))脲;双(羟丙基)脲;N,N’-二羟甲基脲;N,N’-二羟乙基脲;N,N’-二羟丙基脲;N,N,N’-三羟乙基脲;四(羟甲基)脲;四(羟乙基)脲;四(羟丙基)脲;N-甲基-N’-羟乙基脲;N-乙基-N,N-N’-羟乙基脲;N-羟丙基-N’-羟乙基脲和N,N’-二甲基-N-羟乙基脲或其混合物。当术语羟丙基出现时,该含义对3-羟基正丙基、2-羟基正丙基、3-羟基异丙基或2-羟基异丙基是通用的。最优选的是羟乙基脲。后者可以以商标Hydrovance作为50%水性液体从ICI的National Starch&ChemicalDivision获得。
当使用时,本发明的化妆品组合物中的取代脲的量在基于所述化妆品组合物总重量的约0.01-约20%且优选约0.5-约15%且最优选约1-约10%的范围,包括其中所包含的所有范围。
当使用阳离子铵化合物和取代的脲时,在最尤其优选的实施方案中,基于化妆品组合物的总重量,使用至少约1-约15%的颗粒外部的甘油,包括其中所包含的所有范围。
本发明的化妆品组合物可包含维生素作为期望的活性物。说明性的维生素是维生素A(视黄醇)以及视黄醇酯如视黄醇棕榈酸酯和视黄醇丙酸酯、维生素B2、维生素B3(烟酰胺)、维生素B6、维生素C、维生素E、叶酸和生物素。还可采用维生素的衍生物。例如,维生素C衍生物包括四异棕榈酸抗坏血酸酯、抗坏血酸磷酸镁和抗坏血酸糖苷。维生素E的衍生物包括乙酸生育酚酯、棕榈酸生育酚酯和亚油酸生育酚酯。还可采用DL-泛醇和衍生物。当存在于根据本发明的化妆品组合物中时,维生素的总量可在以所述化妆品组合物的重量计0.001-10%、优选0.01-1%、最佳0.05-0.5%的范围。
壬二酸、泛醌、二羟基丙酮(DHA)和其混合物也可用作本发明的化妆品组合物中的活性物。当使用时,此类化合物通常占化妆品组合物的约0.2-10重量%且优选约0.5-5重量%,包括其中所包含的所有范围。
适用于本发明中的其它任选的活性物包括白藜芦醇、间苯二酚如4-乙基间苯二酚、4-己基间苯二酚、4-苯基乙基间苯二酚、二甲氧基甲苯酰基丙基间苯二酚、4-环戊基间苯二酚、4-环己基间苯二酚、α-羟基酸和/或β-羟基酸、苯基乙基间苯二酚(来自Symrise的Symwhite 377)、十一碳烯醇苯基丙氨酸(来自Seppic的Seppi White)、其混合物等。当使用时,此类活性剂共同占化妆品组合物的约0.001-约12重量%。
可存在脱屑促进剂。示例是α-羟基羧酸、β-羟基羧酸。术语“酸”意指不仅包括游离酸,而且还包括其盐和C1-C30烷基酯或芳基酯,以及通过去除水以形成环状或直链内酯化合物而产生的内酯。代表性的酸是乙醇酸和其衍生物、乳酸和苹果酸。水杨酸是β-羟基羧酸的代表。当存在时,这些材料的量可是所述化妆品组合物的约0.01-约15重量%。
各种草本提取物可任选地作为活性物包含在本发明的化妆品组合物中。所述提取物可以是溶剂中携带的分别为亲水性或疏水性的水溶性或水不溶性的物质。水和乙醇是优选的提取溶剂。说明性提取物包括来自绿茶、欧蓍草、甘菊、欧亚甘草、芦荟、葡萄籽、安徽蜜柑(citrusunshui)、柳皮、鼠尾草、百里香和迷迭香的提取物。可使用大豆提取物,尤其是当其满意地包含视黄醇时。
还任选地适合使用的包括材料如螯合剂(例如,EDTA)、C8-22脂肪酸取代的糖、硫辛酸、视黄氧基三甲基硅烷(以Silcare 1M-75商标从Clariant公司获得)、脱氢表雄酮(DHEA)和其组合。还可使用神经酰胺(包括神经酰胺1、神经酰胺3、神经酰胺3B和神经酰胺6)以及假神经酰胺。经常期望有封包剂(Occlusive)如Oilwax LC。这些材料的量可在以所述化妆品组合物的重量计的约0.000001-约10%、优选约0.0001-约3%的范围。
可使用常规的缓冲液/pH调节剂。这些包括常用的添加剂,如氢氧化钠、氢氧化钾、氢氯酸、柠檬酸和柠檬酸盐/柠檬酸缓冲液。在尤其优选的实施方案中,本发明的化妆品组合物的pH为约4至约8,优选约4.25至约7.75,最优选约6至约7.5,包括其中所包含的所有范围。本发明的化妆品组合物可以是固体条或固体棒。然而,本发明的化妆品组合物的粘度优选约1,000至约120,000cp,且最优选约5,000至80,000cp,所述粘度是在环境温度NS和1s-1的剪切速率下,利用以Ares名称从供应商如T.A.Instruments商购的应变控制的平板流变仪测得。
可采用各种各样的包装来储存和递送本发明的化妆品组合物。优选地,包装应当能够容纳或防止在产品的储存和使用期间的任何升高的压力累积。可使用构造成防止或耐受高压累积的泵分配器。
包装经常取决于个人护理最终用途的类型。例如,免洗型皮肤乳剂和霜剂、洗发剂、调理剂和沐浴凝胶通常采用塑料容器,容器在分配端具有由封闭物覆盖的开口。典型的封闭物是螺旋盖、非气溶胶泵和上翻式(flip-top)铰链盖。用于止汗剂、除臭剂和脱毛剂的包装可涉及在分配端上具有滚珠(roll-on ball)的容器。或者,这类个人护理产品可以条状化妆品组合物配制物在具有推进-拉回机构的容器中递送,其中所述条在平台上向分配口移动。通过推进剂加压且具有喷嘴的金属罐用作用于止汗剂、剃须膏和其它个人护理产品的包装。梳妆棒(Toilette bar)可具有由纤维素或塑料包裹材料构成、或在纸板盒内或甚至由收缩性包裹塑料膜构成的包装。
提供以下实施例以促进对本发明的理解。所述实施例并不意在限制权利要求的范围。
实施例1
根据下面的程序,如下表1a至8a中所列配制几种化妆品组合物,并且使用以下描述的改进的挑战方法在相应的表1b至8b中评估其延缓特定微生物生长的效能。使用抗微生物化合物的本发明组合和比较组合制备本发明的化妆品组合物和比较化妆品组合物。
表1a–SF基料对照–LM-16024-93本发明
化合物1:化合物3:
(a)Zeastat以从位于美国宾州Philadelphia的Inolex获得时的那样使用,并且根据制造商其含有80-95重量%的丙二醇和2-20重量%的辛基异羟肟酸。
(b)SymSave H从位于德国Holzminden的Symrise公司获得。
表1b微生物测试结果
表2a–SF基料对照-LM-16024-78比较–不存在羟基苯乙酮
表2b-微生物测试结果
表3a–SF基料对照–LM-16024-79比较–不存在羟基苯乙酮和异羟肟酸
表3b-微生物测试结果
表4a–SF基料对照–LM-16024-80比较–无异羟肟酸
表4b-微生物测试结果
表5a–SF对照–LM-16024-82比较-无异羟肟酸和羟基苯乙酮
表5b-微生物测试结果
表6A–SF24基料对照–LM-16024-83-比较–无羟基苯乙酮和异羟肟酸
表6B–微生物测试结果
表7a–SPF对照–LM-16024-86比较–环烷基化合物,低于0.5重量%
表7b-微生物测试结果
表8a–LM-164024-92比较–无环烷基化合物、羟基苯乙酮和异羟肟酸
表8b-微生物测试结果
使用以下步骤配制表1至8中所示的化妆品组合物。
1.将指定量的去离子水称量至配料器皿中。用IKA-WIERKE仪器(带有L型搅拌器附件的Eurostar Power Control Visc-Stirrer,出厂编号IKA 2600000)开始大的螺旋桨式混合(约200RPM),并加热至75-80℃。
2.添加乙二胺四乙酸二钠和丁基化羟基甲苯并等到它们完全溶解,然后开始添加另外的成分。
3.添加聚合物、甘油、KOH并混合30分钟。
4.如果需要,用50%的氢氧化钠溶液和用于所述配制物全部水体积的10%分别将其它水不溶性成分中和至水相达到pH 5至7.8或8.0,以有效溶解所选择的水不溶性成分,而没有所述化妆品组合物的显著分解或其抗微生物效能的显著降低。
5.在分开的器皿中添加乳化剂和润肤剂。用另一台IKA-WIERKE仪器(带有大型螺旋桨式混合器附件的Eurostar Power Control Visc-Stirrer,出厂编号IKA 2600000)开始轻轻混合,并在水浴中加热至75-80℃。
6.当水相和油相的温度均达到80℃时,开始缓慢地添加油相至水相。
7.用Silverson L4RT-A均质器(型号L4R)以3600rpm将批料热混合1分钟。
8.冷却至40℃并添加苯氧基乙醇、环己醇化合物、羟基苯乙酮和辛基异羟肟酸/丙二醇(Zeastat)。
9.在35℃停止混合。根据需要用DI水补足(Q/S)批料并在冷却清扫(cool sweep)下混合,直至配制物均匀。
进行遵循现行USP第51章的抗微生物有效性测试和M-3-水混溶性个人护理产品的防腐测试方法(CTFA微生物学指南,2007)(USP Chapter 51Antimicrobial EffectivenessTesting and M-3-A Method for Preservative Testing of Water-Miscible PersonalCare Products,CTFA Microbiology Guidelines,2007)的改进的挑战测试。结果在表1b–8b中。所述表示出在每个取样时间点回收的活微生物的数目的对数值。比较样品未能满足测试第7天和测试其余部分所需的2的对数的降低。表1中列出的具有根据本发明的抗微生物组合物的产品满足并且远远超过测试方法的验收准则。
以上测试方法是确定微生物效能的标准测试方法。个人护理产品挑战测试方法基于M-3-用于水混溶性个人护理产品的防腐测试方法CTFA Microbiology Guidelines,2007)。
实施例3.表9至12示出了可与本发明的抗微生物组合物一起使用的若干化妆品上可接受的基料。
表9–阴离子型基质(Chassis)
表10阳离子型基质
(a)1000SUS在100F和210F下的计算厘沲为215.89cSt(2.16×10-5m2/S)和214.41cSt(2.14×10-5m2/S),参见ASTM D2161–10第5.2部分。
表11非离子型基质
表12水/油(反的Invert)基质
成分 | %w/w |
Abil EM 90(鲸蜡基PEG/PPG 10/二甲硅油 | 2.00 |
辛酸甘油三酯/癸酸甘油三酯 | 5.00 |
微晶蜡 | 1.00 |
二甲硅油200液50cst(5×10-5m2/S) | 3.00 |
对羟基苯甲酸丙酯 | 0.10 |
任选的添加剂 | 7.50 |
环聚二甲基硅氧烷DC 245 | 12.00 |
Z-Cote HP-1(氧化锌/三乙氧基辛基硅烷) | 5.00 |
去离子水 | 补足至100 |
EDTA二钠 | 0.05 |
氯化钠 | 0.20 |
甘油(非猪的) | 5.00 |
任选的提取物 | 0.01 |
甘菊提取物 | 0.01 |
Claims (11)
1.一种抗微生物组合物,其包含:
a.一种或多种苯基烷醇或苯基烷氧基化物或其共混物;
b.一种或多种具有其中R为直链烷基的结构(RCONHOH)的异羟肟酸或其共混物;
c.一种或多种羟基苯乙酮或其共混物,和
d.一种或多种选自以下组中的环烷基化合物:环己醇、环己基烷醇、金刚烷醇、金刚烷烷醇、氨基金刚烷、金刚烷铵、降冰片烷醇、降冰片烷烷醇、氨基降冰片烷、降冰片烷铵或其共混物。
2.根据权利要求1所述的抗微生物组合物,其中:
a.至少50%存在的总苯基烷醇和苯基烷氧基化物选自苯氧基乙醇、苄醇、苯乙醇或其共混物;
b.至少50%存在的总异羟肟酸选自C1至C12直链烷基异羟肟酸或其共混物;
c.至少50%存在的总羟基苯乙酮选自4-羟基苯乙酮、3-羟基苯乙酮、2-羟基苯乙酮或其共混物;
d.至少50%存在的总环烷基化合物具有I、II、III的结构或其任意组合:
I.
II.
III.
其中
R1=-OH、-OCH3、-OCH2CH3、-NH2、NH(CH3)、-N(CH3)2、-N+(CH3)3X-(X=F、Cl、Br、I)
R2=-COOCH2CH3、-H
R3=-H、-OH、-OCH3
R4=C6H11-CH-OH;C6H11-CH-OCH3-;C6H5-CH-OCH2CH3;
4 C6H11-CH-OCH2CH3。
3.根据前述权利要求中任一项所述的抗微生物组合物,其中:
a.所述苯基烷醇或苯基烷氧基烷醇或两者的总量浓度为0.1-25重量%;
b.所述异羟肟酸的总量浓度为约0.1-25重量%;
c.所述羟基苯乙酮的总量浓度为约0.1-25重量%;
d.所述环烷基化合物的总量浓度为约0.1-25重量%;并且
e.相容性载体的总量浓度约99.4-0重量%。
4.根据前述权利要求中任一项所述的抗微生物组合物,其中所述环烷基化合物选自以下的化合物(1)至(14)或其共混物:
5.根据权利要求4所述的抗微生物组合物,其中所述环烷基化合物包括化合物(1)、化合物(3)或其共混物。
6.一种化妆品组合物,其包含:
a.化妆品上可接受的基料;和
b.根据权利要求1至5所述的抗微生物组合物。
7.根据权利要求6所述的化妆品组合物,其中所述抗微生物组合物以在第21天使用改进的挑战测试而有效地至少抑制99%的至少一种活微生物再生长的量存在,其中所述微生物选自洋葱伯克霍尔德氏菌(B.cepacia)、铜绿假单胞菌(P.aeruginosa)、恶臭假单胞菌(P.putida)、金黄色葡萄球菌(S.aureus)、白色念珠菌(C.albicans)和巴西曲霉(A.brasiliensis)或其任意组合。
8.根据权利要求6和7所述的化妆品组合物,其中:
a.所述苯基烷醇、苯基烷氧基烷醇或其共混物基于所述化妆品组合物的总量浓度为约0.2-1.0重量%;
b.所述异羟肟酸基于所述化妆品组合物的总量浓度为约0.1-1.2重量%;
c.所述羟基苯乙酮基于所述化妆品组合物的总量浓度为约0.1-1.0重量%;
d.所述环烷基化合物基于所述化妆品组合物的总量浓度为约0.5-1.0重量%。
9.根据权利要求6至8所述的化妆品组合物,其中存在的总异噻唑啉酮抗微生物化合物基于所述化妆品组合物的重量的总量最大量为0.15重量%。
10.一种在化妆品组合物中防止选自革兰氏阴性细菌、革兰氏阳性细菌、酵母菌和霉菌微生物的至少一种微生物或其任意组合生长的方法,其包括以下步骤:
a.制备化妆品上可接受的基料;和
b.共混所述基料与根据权利要求1所述的抗微生物组合物,直至均匀。
11.一种用化妆品组合物处理皮肤的方法,其包括向所述皮肤施用根据权利要求6至9所述的组合物的步骤。
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