CN116157111A - 保湿的抗菌组合物 - Google Patents
保湿的抗菌组合物 Download PDFInfo
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- CN116157111A CN116157111A CN202180063531.3A CN202180063531A CN116157111A CN 116157111 A CN116157111 A CN 116157111A CN 202180063531 A CN202180063531 A CN 202180063531A CN 116157111 A CN116157111 A CN 116157111A
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- Prior art keywords
- antimicrobial composition
- oil
- sensory
- antimicrobial
- acid
- Prior art date
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Abstract
一种透明抗菌组合物包含水、醇、保湿剂和感官油。制备透明抗菌组合物的方法包括将感官油和保湿剂组合形成第一相;将水和醇组合形成第二相;将第一相和第二相组合形成第三相;和将中和剂加入第三相中,由此形成抗菌组合物。
Description
技术领域
本文公开了一种抗菌组合物,具体地,透明保湿抗菌组合物。该透明保湿抗菌组合物包括水、醇、保湿剂和感官油(sensory oil)。
背景技术
消费者越来越关注微生物和病毒污染。因此,卫生一直是消费者所需的最重要属性之一。消费者期望将提供所需卫生特性的产品。全世界的消费者使用不同类型的抗菌组合物来消毒各种表面,包括硬表面,如台面、地板和家具;软和多孔的表面,如衣服、地毯和室内装饰品;和个人表面,如皮肤和毛发。在这样的表面上发现许多微生物,如细菌和病毒。希望的是保持这些表面不含细菌,以使生病的风险最小化。
许多抗菌产品是可商购的。一些作为含有至少60重量%或更多乙醇的凝胶、液体或液体喷雾剂提供。虽然已知此类产品在施用后产生良好的抗菌益处,但某些消费者避免使用基于高乙醇的产品,因为此类产品可能使皮肤干燥、削弱表皮屏障并加速老化过程。在目前的环境中,消费者可能全天在他们的身体上使用抗菌产品,因此增加了发生皮肤干燥的可能性。
因此,一直需要开发一种抗菌组合物,其提供优异的抗微生物和抗病毒益处,同时安全和足够温和以在整个一天中无时间限制地使用。鉴于消费者的需求,对开发一种在局部施用时也递送舒缓和保湿有益效果的抗菌组合物越来越感兴趣。
发明内容
在各个方面中公开了保湿的抗菌组合物。
透明抗菌组合物包含:水;醇;保湿剂;和感官油。
一种制备透明抗菌组合物的方法,包括:将感官油与保湿剂组合形成第一相;将水和醇组合形成第二相;将第一相和第二相组合形成第三相;和将中和剂加入第三相中,从而形成抗菌组合物。
下面更具体地描述这些和其他特征和特性。
具体实施方式
本文公开了一种抗菌组合物。该抗菌组合物是具有非粘性感官特性的透明组合物。抗菌组合物可以是任何形式,但优选是透明液体喷雾剂的形式。抗菌组合物为其所施用于其上的表面提供保湿。例如,在将组合物施用于人体皮肤时,抗菌组合物不会使使用者皮肤干燥,而是使使用者皮肤既被润湿又被消毒。抗菌组合物可以向其所施用的表面提供小于或等于8小时的保湿。抗菌组合物还可以提供针对细菌、病毒和真菌的抗微生物和抗病毒保护。抗菌组合物包括水、醇、保湿剂和感官油。出乎意料地发现,抗菌组合物在施用后提供保湿而没有粘性。这是意想不到的益处,因为抗菌组合物通常需要使用防粘剂来减少通常与抗菌组合物应用相关的粘着感。
抗菌组合物可以基本上不含防粘剂。基本上不含防粘剂是指组合物含有小于2重量%的防粘剂,优选地小于1重量%的防粘剂,更优选小于0.5重量%的防粘剂,甚至更优选小于0.1重量%的防粘剂,还更优选0重量%的防粘剂。本文通篇提及的重量百分比(重量%)是指总组合物中的重量%。
抗菌组合物有利地为其所施用的表面提供保湿和消毒益处。如本文所用的消毒或抗菌组合物是指能够杀死细菌或抑制细菌生长的组合物。抗菌组合物可以基本上不含乳化剂。抗菌组合物可以是透明或半透明的,优选地抗菌组合物是透明的。基本上不含乳化剂是指组合物含有小于2重量%的乳化剂,优选小于1重量%的乳化剂,更优选小于0.5重量%的乳化剂,甚至更优选小于0.1重量%的乳化剂,还更优选0重量%的乳化剂。
抗菌组合物包含8至30重量%、优选10至25重量%、更优选10至20重量%的量的水。
醇可用作组合物中的抗菌剂。当使用醇作为抗菌剂时,抗菌组合物包含60至80重量%、优选62至75重量%、更优选65至75重量%的量的醇,包括其中包含的所有值和范围。醇可以包括多种醇,包括但不限于乙醇、丙醇(正丙醇)、异丙醇或其组合。可以基于醇的纯度百分比来调节抗菌组合物中存在的醇的水平。例如,如果使用纯度为92%的乙醇,则乙醇可以70至80重量%,例如75重量%的量使用。任选地,醇可以包括氯二甲酚。优选的醇可以是变性SD-40乙醇。
抗菌组合物可任选地包含一种或多种另外的抗菌剂。任选的另外的抗菌剂可选自萜烯、精油或在25℃下在水中的溶解度小于百万分之2000(ppm)的阳离子油。可用于本文公开的抗菌组合物中的芳香族精油的实例包括水杨酸戊酯、香芹酚、伞花烃(例如对伞花烃)、二氢丁子香酚、丁子香酚、己基丁子香酚、水杨酸己酯、异丁子香酚、甲基丁子香酚、甲基异丁子香酚、水杨酸甲酯、叔丁基甲酚、百里酚、香豆素、依兰(ylang)、依兰、柯巴巴油(copaiba oil)和香草醛。萜类化合物的非芳族精油的实例包括雪松烷、桉叶油素、柠檬醛(包括香叶醛和橙花醛)、香茅醛、nitronelol、桉树脑(即,1,8桉叶油素)、对二氢芳樟醇、二氢月桂烯醇(DH月桂烯醇)、金合欢醇、香叶醇、己基肉桂醛、羟基香茅醇、羟基香茅醛、异柠檬醛、柠檬烯,优选d-柠檬烯、芳樟醇、长叶烯、薄荷醇、橙花醇、橙花内酯二醇、蒎烯,例如α-蒎烯、水芹烯、萜品烯(terpinine),例如α-萜品烯和γ-萜品烯、萜品醇,例如γ-萜品烯和萜品-4-醇,以及四氢月桂烯醇(THM)。
优选的阳离子油包括季铵阳离子植物油和具有式(CH3)3-Si[Si(CH3)2-O]-[Si(CH3)-((CH2)3-NH-(CH2)2-NH2)-O]2-Si-(CH3)3的带电氨基聚二甲基硅烷。优选的是这些另外的抗菌剂的溶解度在25℃下小于2000ppm。例如,另外的抗菌剂可以是萜品醇、百里酚、丁子香酚、冰片、柠檬烯或其组合。优选的另外抗菌剂可以是萜品醇、百里酚或丁子香酚,或其组合。
其它类型的任选的另外抗菌剂包括银化合物。银化合物可包含银离子,例如,银离子可选自硝酸银、乙酸银、氧化银、硫酸银或其组合。优选地,银化合物是硝酸银。
更具体地讲,任选用于组合物中的银化合物是一种或多种水溶性银(I)化合物,其具有至少1.0×10-4mol/L的银离子溶解度(在25℃的水中)。如本文所提及的,银离子溶解度是衍生自在25℃的水中的溶度积(Ksp)的值,这是许多来源中报道的众所周知的参数。更具体地,银离子溶解度[Ag+](以mol/L给出的值)可以使用下式计算:
[Ag+]=(Ksp·x)(1/(x+1)),
其中Ksp是所关注的化合物在25℃水中的溶度积,并且x表示每摩尔化合物的银离子的摩尔数。已发现了具有至少1×10-4mol/L的银离子溶解度的银(I)化合物对于用于本发明中是理想的。
在银化合物中,期望用于本发明中的是氧化银、硝酸银、乙酸银、硫酸银、苯甲酸银、水杨酸银、碳酸银、柠檬酸银和磷酸银,或其组合,优选地其中银化合物是硝酸银、乙酸银、氧化银、硫酸银或其组合。
当存在时,另外的抗菌剂可以以总抗菌组合物的0.05至2重量%,例如0.1至2重量%的量包括,包括其中包含的所有值和范围。
感官油可用于抗菌组合物中,以帮助在施用组合物后对使用者皮肤留下非粘性感觉。抗菌组合物包含0.01至10重量%、优选0.5至5重量%(包括其中包含的所有值和范围)的量的感官油。感官油可包含可溶性感官油。期望用于本文公开的抗菌组合物中的感官油必须满足以下标准:感官油必须是液体,感官油必须可溶于至少75/25或更高比率的EtOH/水中,这反映了在最终组合物中的溶解度以得到澄清的最终抗菌组合物,并且感官油对于水必须没有溶解力。
可溶性感官油可包含二羧酸酯、乳酸酯、脂肪醇、(聚)丙二醇脂肪醚或其组合。感官油还可包含可溶性感官油和不溶性感官油的混合物,条件是该组合可溶于最终用途组合物中。例如,可溶性感官油可包含己二酸二异丙酯、癸二酸二异丙酯或苹果酸二乙基己酯、乳酸月桂酯、乳酸肉豆蔻酯、乳酸鲸蜡酯、异硬脂醇、PPG14丁基醚、PPG15硬脂基醚或其组合。
上述物质与油(如甘油三酯,如癸酸/辛酸甘油三酯,或大豆油,或脂肪酯,如肉豆蔻酸异丙酯或棕榈酸异丙酯)的进一步组合也在范围内,条件是它们是可溶的并形成透明的最终用途组合物。后者不限制可用于本文公开的组合物中的不溶性油的选择。也就是说,可以使用其他不溶性油,条件是当与本发明组合物的所选感官油组合时,不溶性油在与最终用途组合物混合时变得可溶。抗菌组合物中使用的感官油的任何组合不应影响抗菌组合物的透明度。
除本文先前所述的那些之外,抗菌组合物可另外含有其它成分,包括但不限于皮肤有益剂、芳香剂、防腐剂、表面活性剂、固定剂、遮光剂、螯合剂、增稠剂、保湿剂、结构化剂、染料或着色剂,或其组合。例如,各种着色剂可任选地用于抗菌组合物中。当存在时,着色剂的量可以是抗菌组合物的0.00001至0.005%重量,例如0.0001至0.003%重量,例如抗菌组合物的0.001%重量,包括其中包含的所有值和范围。
例如,保湿剂可任选地用于抗菌组合物中以向组合物提供额外的保湿特性。希望用于抗菌组合物的此类保湿剂可包括水溶性多元醇,如丙二醇、二丙二醇、聚丙二醇(例如PPG-9)、聚乙二醇、羟丙基山梨糖醇、山梨糖醇、己二醇、1,3-丁二醇、1,4-丁二醇、1,2-辛二醇、1,2-己二醇、异戊二醇、1,2,6-己三醇、乙氧基化甘油、丙氧基化甘油及其组合。最优选的是甘油、丁二醇、丙二醇、聚乙二醇、山梨糖醇、聚甘油、异戊二醇、透明质酸或其组合。保湿剂可以以抗菌组合物的1至10重量%、优选2至9重量%、更优选3至8重量%的量存在。
抗菌组合物可任选地含有表面活性剂,例如阳离子表面活性剂。当使用时,阳离子表面活性剂仅限于其应当能够用于局部施用于人体皮肤上。阳离子表面活性剂可包含支链或直链烷基三甲基铵化合物、烷醇三甲基铵化合物或其组合。烷醇三甲基铵化合物包括月桂酰乙基三甲基铵甲基硫酸盐、棕榈酰乙基三甲基铵甲基硫酸盐、硬脂酰乙基三甲基铵甲基硫酸盐、肉碱、棕榈酰肉碱、其组合等。所用的三甲基铵化合物可以是烷基三甲基铵化合物,包括鲸蜡基三甲基氯化铵、鲸蜡基三甲基溴化铵、肉豆蔻基三甲基氯化铵、肉豆蔻基三甲基溴化铵、山嵛基三甲基铵甲基硫酸盐、椰油基三甲基铵甲基硫酸盐、山嵛基三甲基氯化铵、山嵛基三甲基溴化铵、硬脂基三甲基氯化铵、硬脂基三甲基溴化铵、月桂基三甲基氯化铵、月桂基三甲基溴化铵、其组合等。为避免疑义,本文公开的抗菌组合物中使用的阳离子表面活性剂可基本上由上述表面活性剂的任何组合组成或由上述表面活性剂的任何组合组成。
关于包含二甲基铵化合物的阳离子表面活性剂,这种化合物包括二烷基二甲基铵化合物,如二硬脂基二甲基氯化铵、二癸基二甲基氯化铵、二椰油基二甲基氯化铵、其组合等。适合使用的其它二甲基铵化合物包括苄索氯铵和/或苯扎氯铵。本文所用的二甲基铵和三甲基铵化合物意在包括其盐,尤其是其氯化物和溴化物。
还可以使用聚季铵盐材料,并且可以包括如聚季铵盐-6、聚季铵盐-10、聚季铵盐-16、聚季铵盐-45、聚季铵盐-28、聚季铵盐-53、聚季铵盐-67、丙烯酰胺丙基-三甲基氯化铵/丙烯酸酯(或丙烯酰胺)共聚物、其组合等的材料。
基于组合物的总重量,组合物中使用的阳离子表面活性剂(即阳离子三甲基铵、二甲基铵)和/或聚季铵盐材料的量通常为0.007至5重量%,且优选0.01至3重量%,最优选0.05至1重量%,包括其中包含的所有值和范围。
当使用三甲基铵和二甲基铵表面活性剂时,它们通常以1:99至99:1,优选30:70至70:30,最优选40:60至60:40的重量比使用。
抗菌组合物还可任选地包含防晒剂和光稳定剂,条件是所用防晒剂和光稳定剂的类型和量不影响组合物的透明度。使用的防晒剂和光稳定剂包括如辛基甲氧基肉桂酸酯(OMC)、水杨酸乙基己酯、苯基苯并咪唑磺酸(Ensulizole)、对甲氧基肉桂酸乙基己酯(可作为Parsol获得)、阿伏苯宗(丁基甲氧基二苯甲酰基甲烷)(可作为Parsol/>获得)、二苯甲酮-3(也称为羟苯甲酮)和二苯甲酮-4(也称为舒利苯酮)的这类材料。再其它的可以包括双乙基己氧基苯酚甲氧基苯酚三嗪、2-乙基己基-2-氰基-3,3-二苯基-2-丙酸、甲酚曲唑三硅氧烷、3,3,5-三甲基环己基2-羟基苯甲酸酯、2-乙基己基-2-羟基苯甲酸酯或其组合。可以使用无机防晒活性物质,如可以使用微细二氧化钛(优选地粒径小于150纳米(nm),且最优选小于100nm)和氧化锌,聚乙烯和各种其它聚合物也是合适的防晒剂。适用的其它防晒剂包括对氨基苯甲酸(PABA)、辛基二甲基-PABA、2-乙氧基乙基对甲氧基肉桂酸酯、二苯甲酮-1、二苯甲酮-2、二苯甲酮-6、二苯甲酮-8、二苯甲酮-9、二苯甲酮-12、高水杨酸甲酯、邻氨基苯甲酸薄荷酯、二苯甲酮-4、三乙醇胺水杨酸盐、对苯二亚甲基二樟脑磺酸、双辛三唑(bisoctriazole)、双乙基己氧基苯酚甲氧基苯基三嗪、苯基二苯并咪唑四磺酸(bisdisulizole)二钠、diometriazole三硅氧烷、辛基三嗪酮、二乙基己基丁酰胺基三嗪酮(iscotrizinol)、聚硅酮-15、异戊烯基-4-甲氧基肉桂酸酯或其组合。也可以使用奥克立林。当存在时,防晒剂或光稳定剂的量可以是抗菌组合物的0.001至20重量%,优选0.005至15重量%,更优选0.01至0.2重量%,甚至更优选0.1重量%,包括其中包含的所有值和范围。/>
理想地,用于本文公开的抗菌组合物中的任选的皮肤有益剂包括烟酰胺(维生素B3)、生育酚(维生素E)、芦荟、α-羟基酸和酯、β-羟基酸和酯、羟乙基脲、多羟基酸和酯、肌酸、氢醌、叔丁基氢醌、桑葚、透明质酸及其盐(包括但不限于其Na+和K+盐)、提取物、甘草提取物、间苯二酚衍生物或其组合。此类皮肤益处可包括但不限于伤口愈合有益效果,如愈合、干燥减轻、抗灰黄等。例如,皮肤有益剂可为透明质酸钠。基于抗菌组合物的总重量,包括透明质酸钠的此类有益剂可以0.0001至10重量%,例如0.001至6.5重量%,例如0.01至3.5重量%,并且例如0.01重量%的量存在,并且包括其中包含的所有值和范围。
其它任选的水溶性皮肤有益剂包括酸,例如氨基酸,如精氨酸、缬氨酸、组氨酸、赖氨酸、天冬氨酸、苏氨酸、丝氨酸、谷氨酸、脯氨酸、甘氨酸、丙氨酸、异亮氨酸、亮氨酸、酪氨酸或苯丙氨酸。可使用其他维生素,如维生素B2、吡啶酰胺、泛醇(维生素B5)、维生素B6、维生素C、其组合等。还可以使用衍生物(通常是指已经从其他物质开发或获得的一些),尤其是这些维生素的水溶性衍生物。例如,维生素C衍生物,如抗坏血酸四异棕榈酸酯、抗坏血酸磷酸镁和抗坏血酸糖苷可以单独使用或彼此组合使用。烟酰胺衍生物,如烟酰胺腺嘌呤二核苷酸(NADH)和烟酰胺腺嘌呤二核苷酸磷酸(NADPH),可以单独使用或彼此组合使用。可使用的其它皮肤有益剂包括4-乙基间苯二酚,提取物如鼠尾草、芦荟、绿茶、甘蔗、柑橘、葡萄籽、百里香、洋甘菊、蓍草、黄瓜、甘草、迷迭香提取物,或其组合。也可以使用电解质,如NaCl和/或KCl、MgCl2。当存在于本文公开的组合物中时,任选的水溶性有益剂(包括混合物)的总量可以是基于抗菌组合物总重量的0.0001至10重量%,优选0.001至6.5重量%,并且最优选0.01至3.5重量%,并且包括其中包含的所有值和范围。
任选地包括油溶性有益剂也在抗菌组合物的范围内。可以任选地用于本文公开的抗菌组合物中的油溶性有益剂的类型的示例性实例包括如硬脂酸、维生素如维生素A、D、E和K(及其油溶性衍生物)的组分。
使用的其它任选的油溶性有益剂包括间苯二酚类和间苯二酚衍生物,如4-己基间苯二酚、4-苯乙基间苯二酚、4-环戊基间苯二酚、4-环己基间苯二酚、4-异丙基间苯二酚或其组合。此外,可以使用5-取代的间苯二酚,如4-环己基-5-甲基苯-1,3-二醇、4-异丙基-5-甲基苯-1,3-二醇,其组合等。5-取代的间苯二酚及其合成描述于共同受让的美国公开专利申请No.2016/0000669A1中。
甚至可使用的其它油溶性有益剂包括ω-3脂肪酸、ω-6脂肪酸、氯咪巴唑、厚朴酚、和厚朴酚、法呢醇、熊果酸、肉豆蔻酸、香叶基香叶醇、油基甜菜碱、椰油酰基羟乙基咪唑啉、己酰基鞘氨醇、12-羟基硬脂酸、岩芹酸、共轭亚油酸、硬脂酸、棕榈酸、月桂酸、萜品醇、百里酚精油组分、,溶解助剂,其选自柠檬烯、蒎烯、莰烯、伞花烃、香茅醇、香茅醛、香叶醇、橙花醇、芳樟醇、玫瑰醇、冰片、异冰片、薄荷酮、樟脑、黄樟素、异黄樟素、丁子香酚、异丁子香酚、茶树油、桉树精油、薄荷油、苦楝油、柠檬草油、橙油、佛手柑油或其组合。
可以使用的另一种任选的油溶性有益剂是视黄酸前体。视黄酸前体可以是视黄醇、视黄醛、视黄酯、丙酸视黄酯、棕榈酸视黄酯、乙酸视黄酯或其组合。丙酸视黄酯、棕榈酸视黄酯及其组合通常是优选的。使用的再另一种视黄酸前体是由Molecular DesignInternational提供的以商品名商购的羟基茴香醚视黄酸酯。其可与本文所述的任何油溶性有益剂组合使用。
当在抗菌组合物中使用任选的(即0.0至1.5重量%)油溶性有益剂时,其通常以最终用途组合物总重量的0.001至1.5重量%,并且例如0.05至1.2重量%,例如0.2至0.5重量%的量存在,包括其中包含的所有值和范围。
成膜剂可用于抗菌组合物中。虽然是任选的,但此类试剂可有助于组合物粘附于其所施用的表面。成膜剂包括具有亲水性能的那些,并且它们包括包含聚乙烯吡咯烷酮(PVP)、丙烯酸酯、丙烯酰胺及其共聚物的材料。也可以使用沉积剂,如有机硅氧烷和聚季铵盐-7(来自Lubrizol的MerquatTMS聚合物)。当使用时,这些试剂占抗菌组合物的0.001至1重量%,包括其中包含的所有值和范围。
可用于组合物中的其它任选组分是抗蚊剂,如桉树油、薰衣草油、N,N-二乙基-间甲苯酰胺(DEET),其组合等。可以使用的甚至其它成分包括羟甲辛吡酮(吡罗克酮)、吡啶硫酮锌、氯二甲苯酚、三氯生、氯化十六烷基吡啶鎓以及银化合物,包括氧化银、硝酸银、硫酸银、磷酸银、碳酸银、乙酸银、苯甲酸银,其组合等。如果使用,这些其它组分通常占抗菌组合物的0.001至1.6重量%,优选0.01至1.2重量%,包括其中包含的所有值和范围。
任选地,防腐剂可用于本文公开的抗菌组合物中。当使用时,使用的示例性防腐剂包括苯甲酸钠、碘代丙炔基丁基氨基甲酸酯、苯氧乙醇、羟基苯乙酮、乙基己基甘油、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、咪唑烷基脲、脱氢乙酸钠、二甲基-二甲基(DMDM)乙内酰脲和苄醇,或其组合。适合使用的其它防腐剂包括脱氢乙酸钠、氯苯甘油醚和癸二醇。防腐剂优选以抗菌组合物总重量的0.01%至2.0重量%的量使用,包括其中包含的所有值和范围。还优选的是具有单独的羟基苯乙酮或与其他防腐剂的混合物的防腐剂体系。
芳香剂、固定剂、遮光剂(如二氧化钛或二醇二硬脂酸酯)、螯合剂可任选地包括在抗菌组合物中。可能的螯合剂包括但不限于乙二胺四乙酸(EDTA)、二亚乙基三胺五乙酸(DTPA)、乙二胺二琥珀酸(EDDS)、二亚乙基三胺五乙酸五钠、N-(羟乙基)-乙二胺三乙酸三钠、EDTA的酸形式、硫氰酸钠、甲基甘氨酸二乙酸三钠盐、谷氨酸二乙酸四钠和植酸,优选地其中螯合剂是乙二胺四乙酸(EDTA)、二亚乙基三胺五乙酸(DTPA)、乙二胺二琥珀酸(EDDS)或其组合。这些物质中的每一种可以以抗菌组合物的总重量的约0.03重量%至约3重量%,优选约0.1重量%至约2.6重量%的量存在,包括其中包含的所有值和范围。
期望使用的另一种任选的添加剂包括具有2.5至25重量%的大麻萜酚和/或0.5至10重量%的大麻二酚的大麻油。当使用时,这种油占抗菌组合物的0.0001至1.5重量%,并且如果使用的话,优选占抗菌组合物的0.01至1重量%,包括其中包含的所有值和范围。
为了调节抗菌喷雾组合物的粘度,任选地包括少量的增稠剂在组合物的范围内。任选使用的是归类为多糖的增稠剂。实例包括纤维、淀粉、天然/合成树胶和纤维素类。代表性的淀粉是化学改性淀粉,如羟丙基淀粉磷酸钠和淀粉辛烯基琥珀酸铝。通常优选木薯淀粉,麦芽糊精也是如此。树胶包括黄原胶、塔拉胶、菌核胶、果胶、刺梧桐树胶、阿拉伯树胶、琼脂、瓜尔胶(包括阿拉伯胶瓜尔胶)、角叉菜胶、藻酸盐及其组合。纤维素类包括羟丙基纤维素、羟丙基甲基纤维素(例如,Ashland的BENECELTME10M)、乙基纤维素、羧甲基纤维素钠(纤维素胶/羧甲基纤维素)和纤维素(例如,纤维素微纤丝、纤维素纳米晶体或微晶纤维素)。纤维素微纤丝的来源包括次生细胞壁材料(例如木浆、棉花)、细菌纤维素和初生细胞壁材料。优选地,初生细胞壁材料的来源选自来自果实、根、鳞茎、块茎、种子、叶及其组合的薄壁组织;更优选选自柑橘类果实、番茄果实、桃果实、南瓜果实、猕猴桃果实、苹果果实、芒果果实、甜菜、甜菜根、芜菁、欧洲防风、玉米、燕麦、小麦、豌豆及其组合;并且甚至更优选地选自柑橘果实、番茄果实及其组合。初生细胞壁材料的最优选来源是来自柑橘果实的薄壁组织。柑橘纤维,如可由作为AQ Plus得到的那些,也可用作纤维素微纤丝的来源。纤维素来源可以通过任何已知方法进行表面改性,包括在Colloidal PolymerScience,Kalia等,“Nanofibrillated cellulose:surface modification and potentialapplications”(2014),第292卷,第5-31页中描述的那些。
可以包括的其它增稠剂可以包含疏水改性的交联聚合物。合成聚合物是有效的增稠剂。可能的增稠剂包括交联的聚丙烯酸酯,如卡波姆,如ASHLANDTM980卡波姆(丙烯酸的交联聚合物)、丙烯酸酯共聚物、丙烯酸酯/丙烯酸酯(C10-C30)烷基丙烯酸酯交联聚合物,如系列,如Ultrez20和ETD2020,其可从Lubrizol商购获得,INCI名称为丙烯酸酯/C10-30丙烯酸烷基酯交联聚合物。来自Lubrizol/>系列的再其他聚合物可包括Ultrez 10、Ultrez 21等。聚丙烯酰胺如/>305和牛磺酸盐共聚物如EG和/>AVC,该共聚物通过各自的INCI命名被标识为丙烯酸钠/丙烯酰二甲基牛磺酸钠和丙烯酰基二甲基牛磺酸/乙烯基吡咯烷酮共聚物。再其他的增稠聚合物可包括合成聚合物,如可由Seppic商购获得并以名称Simulgel INS100销售的基于丙烯酸酯的聚合物。还可以使用碳酸钙、热解二氧化硅和硅酸镁铝。
当使用时,增稠剂的量可以为抗菌组合物的0.001至5重量%的范围。麦芽糊精、黄原胶和羧甲基纤维素是通常优选的增稠剂。通常期望的其它增稠剂是二亚油基/二甲基碳酸酯共聚物、硬脂基烷铵锂蒙脱石、鲸蜡基(鲸蜡硬脂酰基,硬脂酰基)脂肪醇、塔拉胶、聚季铵盐32和/或37、季戊四醇四硬脂酸酯或其组合。
抗菌组合物可任选地含有乳化剂。乳化剂可选自具有以下的那些:与约2至约100摩尔环氧乙烷或环氧丙烷/摩尔疏水物缩合的C10-C20脂肪醇或酸疏水物;与2至20摩尔环氧烷缩合的C2-C10烷基酚;乙二醇的单脂肪酸酯和二脂肪酸酯;f;脱水山梨糖醇,单-和二C8-C20脂肪酸;和聚氧乙烯脱水山梨糖醇,或其组合。烷基多糖苷和糖脂肪酰胺(例如甲基葡糖酰胺)也可用作非离子乳化剂。
优选的乳化剂通常具有7.5至28,且优选8至25,最优选9至20的HLB(亲水-亲油平衡),包括其中包含的所有范围,例如非离子乳化剂可包括聚山梨醇酯20(吐温20)、聚氧乙烯(20)脱水山梨糖醇单油酸酯(吐温80)。当存在时,乳化剂可以以0至1重量%,例如1重量%的量存在,包括其中包含的所有值和范围。
抗菌组合物可另外含有中和剂,如氢氧化钠、氢氧化钾、三乙醇胺、铵、精氨酸、氨丁三醇,由Angus以AMP 95、AMP-Ultra PC1000、AMP-Ultra PC2000、AMP-Ultra PC3000出售的氨甲基丙醇,来自BASF的也称为Neutrol TE的四羟基丙基乙二胺、二异丙醇胺、三异丙醇胺或其组合。中和剂可以0至1重量%,例如0.1至0.75重量%,例如0.2至0.5重量%的量存在,包括其中包含的所有值和范围。
关于包装,抗菌组合物可以包装在喷雾瓶、挤压瓶中,或作为棉签、擦拭物、毛巾、化妆品基材片(如US 6,294,182B1中所述的那些)等上的浸渍湿润剂提供。因为用增稠剂增加了粘度,抗菌组合物凝胶化并且可以在挤压瓶中作为凝胶组合物提供给消费者。喷雾瓶也可以是金属的,并且抗菌组合物可以通过常规的气溶胶包装技术提供,并且包括利用袋内空气(air-in-bag)排放罐、机构和致动器的那些技术。包括发泡剂(例如,两性离子和/或两性表面活性剂)以使得抗菌组合物可以作为泡沫排出也在抗菌组合物的范围内。
抗菌组合物应提供有将组合物施用(例如,挤压或喷雾)到表面(如皮肤)上以杀死细菌和减少病毒活性的说明书。抗菌组合物可以在可生物降解的包装中提供,并且所使用的包装优选是可再填充的或可重复使用的、可生物降解的,和/或至少50%,优选至少100%由消费后再循环树脂制成。抗菌组合物可以是液体或凝胶的形式,优选地抗菌组合物是液体的形式,例如液体喷雾抗菌组合物。
如本文所用,皮肤意指包括手臂(包括腋下)、面部、足部、颈部、胸部、手部、腿部、臀部和头皮(包括毛发)上的皮肤。如本文所用的消毒是指在局部施用于表面后少于3分钟内,至少2的细菌对数杀灭和至少2的病毒对数灭活(两者均实现),优选至少3的细菌对数杀灭和至少3的病毒对数灭活。如本文所用,组合意指例如西曲氯铵加苯扎氯铵的总重量。皮肤有益剂是指适于改善皮肤特性的成分。如本文所用的表面包括皮肤或无生命物体的表面,如桌面、计算机监视器、门把手、马桶座圈、购物车把手或甚至服装。表面还意指包括动物的皮毛,如狗和猫的毛皮。如本文所用,表面优选是指人皮肤,且尤其是面部和手上的皮肤。
抗菌组合物可以是家庭护理组合物,如适于喷涂需要消毒的衣服和室内装饰品的洗衣喷雾组合物。家庭护理组合物还可以是抗菌厨房或浴室喷雾组合物。优选地,抗菌组合物是通过显著减少皮肤上细菌和病毒的量而施用于皮肤以进行消毒的局部组合物。组合物可任选地包含加入其中的皮肤有益成分,如润肤剂、维生素和/或其衍生物、间苯二酚类、视黄酸前体、着色剂、保湿剂或湿润剂、芳香剂、防晒剂、其组合等,如本文先前所述的。皮肤有益成分可以是水溶性或油溶性的。
因此,抗菌组合物是pH为3.0至8.2的水醇基组合物,并且该组合物是水/醇连续性的。如本文所用的,粘度如下获取:使用Brookfield粘度计(使用转子4以10rpm)或使用Discovery HR-2流变仪(使用具有1000微米间隙的喷砂板及对于第一粘度VA的0.4s-1的第一剪切速率SA和对于第二粘度VB的10s-1的第二剪切速率SB,两者均在25℃下和以20秒间隔进行)。
已知在粘度的情况中使用几种单位,但更经常使用的单位是厘泊(cP)、帕斯卡秒(Pa*s)和毫帕斯卡秒(mPa*s),并且这些单位在公众可获得的资源(如教科书、百科全书和互联网)的帮助下易于相互转换。在再另一个实施方案中,组合物是非治疗和非医药组合物,其是粘度低于10,000厘泊(cP)(10Pa*s),优选粘度低于5,000cP(5Pa*s),优选粘度0.8至3,000cP(0.0008至3Pa*s),更优选粘度为0.8至2,000cP(0.0008至2Pa*s)的水醇溶液。
通常,抗菌组合物的粘度将低于10,000cP(10Pa*s)。通常,抗菌组合物的粘度将为0.8至5,000cP(0.0008至5Pa*s),优选0.8至3,000cP(0.0008至3Pa*s),更优选0.8至2,000cP(0.0008至2Pa*s),还更优选0.8至1,000cP(0.0008至1Pa*s),包括其中包含的所有范围。
抗菌组合物可以通过制备抗菌组合物的任何方法来制备。在一个实施方案中,制备抗菌组合物的方法可包括以下:将感官油和保湿剂组合以形成第一相。然后将水和醇组合以形成第二相。然后将第一相和第二相组合以形成第三相。将中和剂加入第三相中,从而形成抗菌组合物。
实施例
以下实施例仅说明本文公开的抗菌组合物,并不旨在限制其范围。
实施例1:
样品1和2是证明本文公开的抗菌组合物的组成的实施例。
表1-所有数字显示为重量%
可以基于醇的纯度百分比来调节抗菌组合物中存在的醇的水平。例如,乙醇纯度应优选为92%w/w至94%w/w,使得如果使用纯度为92%的乙醇,则乙醇可以70至80重量%,例如72重量%的量使用。
表2显示了可用于抗菌组合物中以设计具有非粘性感觉的透明且快速干燥的手消毒剂喷雾制剂的油。这些实例并不意味着限制可以使用的材料,而仅仅是说明基于三个标准选择的油类型和水平。优选使用的油是在至少75/25EtOH/水共混物中具有大于30%溶解度的油,反映了在样品1中所示的制剂中的良好溶解度。此外,油在室温下必须是液体,使得一旦作为膜留下,组合物不赋予任何负面的感觉。最后,优选的油本身必须不具有对于水的溶解力,使得在施用期间和干燥时,随着乙醇和水蒸发,水也允许快速蒸发,从而仅留下油和任何皮肤有益活性物质/保湿剂(如果存在的话)。不希望受理论束缚,据信具有如本文所公开的优选油的手消毒剂制剂施用于皮肤时并且随着水和乙醇蒸发,如果油对水具有良好的增溶能力,则这将延迟蒸发并驱向于不期望的较慢干燥和较粘的感觉。
表2
表2中示出了满足和不满足三个标准的油的实例,该三个标准包括:(1)油必须是液体;(2)油必须可溶于至少75/25EtOH/水混合物中;(3)油必须对于水没有溶解力,且因此,对于用于所公开的抗菌组合物中是理想的。
实施例2:
样品2的组合物用于测试保湿、复原性伤口愈合测试和黑色素含量。
通过视觉测量(干燥和红斑)和用Skicon和皮肤水份测试仪的仪器水合评估来测量保湿。在基线时、单次受控产品施用后2小时、4小时、6小时和8小时获得了测量值。
从数据可以看出,与基线相比,在所有时间点用样品2的组合物制成的消毒剂显示出水合的改善。与未处理的对照部位相比,用样品2的组合物制成的消毒剂在水合方面也是优异的。
测试样品2并与样品3和4进行比较。样品2至4的制剂显示在表3中。样品4和5是未施用消毒组合物的未处理皮肤。
表3
参与者进入5天的调理阶段,其中他们被指示使用白色皂条用于所有一般沐浴和淋浴,包括测试部位(前臂)。要求参与者在研究期间避免在测试区域上使用任何另外的产品,并且在产品施用和评估阶段之前或期间的两天内避免刮削。还指示参与者在研究前至少12小时沐浴。
在基线访视时,在掌侧前臂上的每个部位上视觉干燥评分为0至2.5且红斑评分≤2.0(0-6量表)且相邻部位之间的等级差异不超过±0.5或总体1.0单位的参与者进入到产品施用阶段。将总共8个测试部位(4cm×4cm)随机分配到参与者的右或左掌侧前臂。处理部位通过延续(carry-over)拉丁方设计在掌侧前臂上的所有部位平衡化。
在产品施用阶段之前,通过专家视觉评估员和水合的仪器评估(Skicon:电导,皮肤水份测试仪:电容)获得对于干燥和红斑的视觉评估的基线评估。在基线测量之后,研究人员进行单次受控产品施用。产品施用程序描述如下:
研究人员使用重复移液管将0.035mL测试产品分配到测试部位。使用戴手套的手指,将测试产品以圆周运动彻底擦到指定的测试部位上,直到该部位完全湿润。然后使该部位风干。
在每个受试者上留下两个测试部位未处理,其形成样品3和4。
然后在施用后2、4、6小时(±15分钟)和8小时(±30分钟)获得干燥度的视觉评估、皮肤水份测试仪和Skicon测量。在评估之前,参与者在保持在66.3°F至70.1°F(19.0℃至21.2℃)和38%至55%相对湿度的房间中适应最少20分钟。一名经训练的评估员在治疗阶段期间进行所有视觉评估。每个仪器使用多于一个受过训练的操作者来收集仪器读数。
使用简单的成对非参数方法(具有Pratt-Lehman调整的Wilcoxon符号秩检验)完成视觉干燥分析,例如评估产品内从基线的变化(CFB)或评估产品对的CFB差异。
对于仪器数据,在每个产品/未处理部位内,使用双尾配对t检验以95%置信水平将每个评估时间点与基线进行比较。仪器测量的处理间分析在每个时间点应用单线性模型(其中CFB作为结果变量,BL作为协变量,并且积(PRODUCT)作为感兴趣的效能),所有产品与所有其他进行比较。对于每个产品的CFB,并且还对所有产品比较进行所有感兴趣的比较。
对于任何样品或未处理部位,在研究期间未观察到视觉红斑。
在用皮肤水份测试仪进行水合评估期间,评估样品2至4。如表4所示,样品3和4在施用后的所有时间点显示出没有从基线的变化或劣化的皮肤水份测试仪水平。样品2在一次施用后的所有时间点显示出改善。
表4:掌侧前臂处的皮肤水份测试仪CM825皮肤水合CFB值
从表2中可以看出,样品2在所有时间点通过皮肤水份测试仪显示出统计学上显著的水合增加。在8小时时间点,样品3和4通过皮肤水份测试仪显示出统计学上显著的水合增加。表5中的“BL”是指基线。基线是测量的起始点。
表5:Skicon 200-EX:皮肤表面水合-CFB,基于掌侧前臂处的Log10转化的值
如表5所示,样品2,本发明的样品在所有时间点显示出通过Skicon的水合的显著增加,并且样品3和4在所有时间点显示出水合的轻微增加。
实施例3
在这个实施例中,测试了有益剂的各种组合的复原性伤口愈合和屏障修复。对于伤口愈合评估,使细胞生长至80%汇合并用生物活性物质处理24至36小时。处理后,在细胞上产生划痕,并在孵育24小时后监测伤口的闭合。划痕区域的闭合计算为伤口的闭合%。以4x的放大倍数捕获显微镜图像,并且将开放伤口区域测量使用软件CellSens分析。以百分比计的伤口闭合=((t=24)处的开放伤口区域的读数的平均值-(t=0)处的开放伤口区域的读数的平均值/(t=0)处的读数的平均值)*100。表6列出了伤口愈合测定的结果。
表6
从表6中可以看出,用维生素B3、维生素E、芦荟和透明质酸钠的组合观察到伤口愈合的显著改善,与维生素B3或维生素E相比统计学上显著的改善。
实施例4
在这个实施方案中,进行黑色素含量测定以确定用如表7所示的有益活性物质的各种组合发现的抑制或黑色素减少。在这个实施例中,使细胞生长24小时并用生物活性物质处理并孵育72小时。处理后,将细胞裂解并在405nm处测量吸光度。将裂解物转移到新鲜的384孔透明平底板中,并使用FlexStation 3读数器在405nm下测量原始直径。(黑色素含量的减少%通过取对照的平均吸光度值-处理细胞的平均吸光度值/对照的平均吸光度值)*100来测量)。
表7
在这个黑色素含量测定中,10微摩尔的4-己基间苯二酚产生约33%的抑制(基准)。在黑色素含量测定中通常认为高于~15%的任何抑制被认为是显著的。因此,从表7可以看出,维生素B3、维生素E和芦荟的组合两种维生素E水平下显示出对黑色素含量的显著抑制。另外,维生素B3、维生素E、芦荟和透明质酸钠的组合显示出对黑色素含量的显著抑制。
在没有另外明确说明的情况下,本文所述的所有范围意在包括其中包含的所有范围。如本文所用,除非明确描述,否则基本上不含意指小于10重量%。抗微生物益处意指在3分钟或甚至10秒内至少2的对数杀灭,优选至少3的对数杀灭,其中抗微生物评估通过ASTM国际标准方法E2783-11(2016年重新批准)测量,该方法阐述了使用时间杀灭程序测量水混溶性化合物的抗微生物活性的程序。如ASTM国际标准方法1052-20中所述,通过评估杀微生物剂对病毒的影响来确定病毒的(或病毒)灭活。术语包含意在涵盖术语基本上由……组成和由……组成。为了避免疑义,并且为了说明,包含水、阳离子表面活性剂和防腐剂的组合物意指包括基本上由其组成的组合物和由其组成的组合物。
除非另有明确说明,否则本说明书中表示材料的量或反应条件、材料的物理性质和/或用途的所有数字应理解为由词语“约”修饰。除非另有说明,否则所有量均按最终组合物的重量计。
应当注意,在指定浓度或量的任何范围时,任何特定的较高浓度可以与任何特定的较低浓度或量以及其中包含的任何子范围相关联。在这方面,应注意,本文公开的所有范围包括端点,并且端点可彼此独立地组合(例如,“最多25重量%,或更具体地,5重量%至20重量%的范围”,包括5重量%至25重量%范围的端点和所有中间值等)。“组合”包括共混物、混合物、合金、反应产物等。此外,本文中的术语“第一”、“第二”等不表示任何顺序、数量或重要性,而是用于将一个要素与另一个要素区分开。除非本文另有说明或与上下文明显矛盾,否则本文中的术语“一个(a)”和“一种(an)”和“该”不表示数量的限制,并且应被解释为涵盖单数和复数。如本文所用的后缀“(s)”旨在包括其修饰的术语的单数和复数两者,从而包括一个或多个术语(例如,膜(s)包括一个或多个膜)。在整个说明书中对“一个实施方式”、“一个方面”、“另一个实施方式”、“另一个方面”、“实施方式”、“方面”等的引用意味着结合该实施方式或方面描述的特定元素(例如,特征、结构和/或特性)包括在本文描述的至少一个实施方式或方面中,并且可以存在或可以不存在于其他实施方式或方面中。另外,应当理解,所描述的要素可以在各种实施方式或方面中以任何合适的方式组合。
所有引用的专利、专利申请和其他参考文献通过引用整体并入本文。然而,如果本申请中的术语与所并入的参考文献中的术语矛盾或冲突,则来自本申请的术语优先于来自所并入的参考文献的冲突术语。虽然已经描述了特定方面,但是或可能目前无法预见的替代、修改、变化、改进和实质性等同物是申请人或本领域其他技术人员可以想到的。因此,所提交的和可能修改的所附权利要求旨在涵盖所有这样的替代、修改、变化、改进和实质性等同物。
为了避免疑义,词语“包含”旨在表示“包括”,但不一定是“由……组成”或“由……构成”。换句话说,所列出的步骤、选项或替代方案不需要是穷尽的。
如本文中发现的本发明的公开内容被认为涵盖如在彼此多重从属的权利要求中发现的所有方面,而不管权利要求可以在没有多重从属或冗余的情况下被发现的事实。除非另有说明,否则以“x至y”形式表示的数值范围应理解为包括x和y。在指定任何范围的值或量时,任何特定的上限值或量可以与任何特定的下限值或量相关联。除非另有说明,否则本文所含的所有百分比和比率均按重量计算。在以上各个部分中提及的本发明的各种特征加以必要的变更适当地适用于其他部分。因此,一个部分中指定的特征可以适当地与其他部分中指定的特征组合。添加任何章节标题仅是为了方便,并不旨在以任何方式限制本公开。
Claims (15)
1.一种透明抗菌组合物,其包含:
水;
醇;
保湿剂;和
感官油。
2.根据前述任一项权利要求所述的抗菌组合物,其中所述感官油包含可溶性感官油,优选地其中所述油必须是液体,所述油必须可溶于至少75/25EtOH/水中,并且所述油必须对于水没有溶解力。
3.根据前述任一项权利要求所述的抗菌组合物,其中所述感官油以0至10重量%,优选地0.5至5重量%的量存在。
4.根据前述任一项权利要求所述的抗菌组合物,其中所述感官油包含二羧酸酯、乳酸酯、甘油三酯、大豆油、脂肪酸酯、(聚)丙二醇脂肪醚或其组合,其中添加所述感官油不影响所述抗菌组合物的透明度。
5.根据权利要求4所述的抗菌组合物,其中所述感官油包含选自己二酸二异丙酯、癸二酸二异丙酯或苹果酸二乙基己酯、乳酸月桂酯、乳酸肉豆蔻酯、乳酸鲸蜡酯、异硬脂醇、PPG15硬脂基醚或其组合的可溶性感官油,选自癸酸/辛酸甘油三酯肉豆蔻酸异丙酯、棕榈酸异丙酯或其组合的不溶性感官油,或所述可溶性感官油和所述不溶性感官油的其组合。
6.根据前述任一项权利要求所述的抗菌组合物,其中所述水以8至30重量%、优选10至25重量%、更优选10至20重量%的量存在,并且其中所述醇以60至80重量%、优选62至75重量%、更优选65至75重量%的量存在。
7.根据前述任一项权利要求所述的抗菌组合物,其中所述醇包含乙醇、异丙醇、正丙醇或其组合。
8.根据前述任一项权利要求所述的抗菌组合物,其中所述保湿剂以1至10重量%、优选2至8重量%、更优选3至7重量%的量存在。
9.根据前述任一项权利要求所述的抗菌组合物,其中所述保湿剂包含甘油、丁二醇、丙二醇、聚乙二醇、山梨糖醇、聚甘油、异戊二醇、透明质酸或其组合。
10.根据前述任一项权利要求所述的抗菌组合物,还包含皮肤有益剂。
11.根据权利要求10所述的抗菌组合物,其中所述皮肤有益剂包括烟酰胺、生育酚、芦荟、透明质酸钠或透明质酸钾、α-羟基酸和酯、β-羟基酸和酯、羟乙基脲、多羟基酸和酯、肌酸、氢醌、叔丁基氢醌、桑树提取物、甘草提取物或其组合。
12.根据前述任一项权利要求所述的抗菌组合物,其中所述抗菌组合物为液体形式,优选地其中所述抗菌组合物为液体喷雾抗菌组合物的形式。
13.根据前述任一项权利要求所述的抗菌组合物,还包含螯合剂,优选地其中所述螯合剂包括乙二胺四乙酸(EDTA)、二亚乙基三胺五乙酸(DTPA)、乙二胺二琥珀酸(EDDS)、二亚乙基三胺五乙酸五钠、N-(羟乙基)-乙二胺三乙酸三钠、硫氰酸钠、甲基甘氨酸二乙酸三钠盐、谷氨酸二乙酸四钠和植酸,优选地其中所述螯合剂是乙二胺四乙酸(EDTA)、二亚乙基三胺五乙酸(DTPA)、乙二胺二琥珀酸(EDDS)或其组合。
14.一种制备透明抗菌组合物的方法,包括:
将感官油和保湿剂组合形成第一相;
将水和醇组合形成第二相;
将所述第一相和所述第二相组合形成第三相;和
将中和剂加入所述第三相中,从而形成所述抗菌组合物。
15.根据权利要求14所述的方法,还包括将芳香剂加入所述抗菌组合物中。
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