CN101553202B - 用于皮肤消毒的温和组合物 - Google Patents
用于皮肤消毒的温和组合物 Download PDFInfo
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- CN101553202B CN101553202B CN200780045590.8A CN200780045590A CN101553202B CN 101553202 B CN101553202 B CN 101553202B CN 200780045590 A CN200780045590 A CN 200780045590A CN 101553202 B CN101553202 B CN 101553202B
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Abstract
本发明公开了一种用于皮肤消毒的水性组合物，所述组合物包含浓度在0.1-10％(w/w)范围内、优选在0.2-6％范围内的过氧化氢以及浓度在0.1-20％(w/w)范围内、优选在0.1-10％范围内、更优选在0.2-8％范围内、最优选在0.2-5％(w/w)范围内的N-酰基化氨基酸和/或肽。所述N-酰基化氨基酸组分可以是N-酰基化谷氨酸和/或N-酰基化小麦蛋白水解产物，或其盐。
Description
本发明涉及一种用于皮肤的消毒、清洁、抗微生物调节和皮脂调节的温和且与皮肤高度相容的、具有生物灭杀活性的组合物。
人类的皮肤总是孳生有大量各种微生物(细菌、酵母和真菌)。存活于皮肤之上或皮肤之中的共生微生物可以形成常驻(正常)或暂驻的微生物群落部分。对皮肤健康有益所必需的常驻微生物菌群主要由葡萄球菌素(Staphylococcus epidermis和Staphylococcus hominis)、棒状菌、革兰氏阳性丙酸杆菌(诸如Propionibacterium acnes)以及主要由Pityrosporum ovale构成的酵母菌群组成。例如据称Pityrosporum ovale与许多皮肤失调症相关，诸如脂溢性皮炎、毛囊炎、融合性网状乳头瘤病和银屑病皮损。
大多数皮肤细菌存在于表层鳞状上皮中，拓殖死细胞并且与脂肪腺和汗腺紧密相关。这些腺体的分泌物主要为Staphylococcus epidermidis和某些需氧棒状菌提供水、氨基酸、脲、电解质以及特定脂肪酸作为营养成分。
皮肤感染通常在致病性外生微生物在皮肤上拓殖后或者在内生菌株发生反常繁殖后由于破坏了常驻菌群的生态平衡而引起。最常见的致病性微生物是Pseudomonas aeruginosa(革兰氏阴性)，其造成小斑、毛囊炎、红斑和骚痒症；Candida albicans，其可以引起嘴角发炎、皮肤念珠菌病、骚痒症、毛囊炎和复发性阿弗他溃疡性口炎；Staphylococcus aureus，其可以造成斑、毛囊炎、脓疱病和疖子；以及A组链球菌，其造成脓疱病。
在许多行业中，对致病性微生物的扩散进行感染控制和预防是一个主要关注的问题。在兽医、保健、辅助医护、医院、食品加工以及工业应用中，预防致病性微生物的污染以及扩散是极为重要的。通常微生物通过手扩散传播。受污染手上的病毒和细菌易于在保健设施(诸如医院)中的人们之间传播。而且在洗手间、保健场所、学校和家庭中，保持较高的卫生标准也变得越来越重要。
用清洁剂或肥皂洗手是降低感染风险的一种方式。然后，在某些环境(诸如医药或食品加工场所)中，常规使用的肥皂和清洗剂不能达到所需消毒水平。因而，需要开发一种具有较高消毒水平的洗手消毒剂。
因此，目前医院设备中和食品卫生部门中感染控制的等级越来越高，``以及对可以通过皮肤和呼吸系统传染的传染性疾病的关注越来越强，这些趋势使所述行业需要一种消毒组合物，这种消毒组合物可以在整天内更频繁使用。这些组合物必须是低变应原性(hypoallergenic)、无毒的，而且不会在皮肤上产生任何不希望的残留物。
目前的皮肤消毒产品通常含有醇、碘酒/碘载体、葡萄糖酸氯己定(chlorhexidine gluconate，CHG)、酚类化合物、三氯生、季铵化合物或其组合，其缺点在于：它们为了达到温和皮肤的目的往往要牺牲消毒活性，反之亦然。例如，尽管提高活性成分的浓度可以获得较高的消毒水平，但是这种较高的浓度往往会导致提高皮肤刺激，尤其在频繁使用时。当前可得化合物中的许多导致皮肤干燥、皮肤刺激、或被认为具有不利副作用。已知且广泛使用的皮肤消毒化合物中的许多受到限制，或者在某些市场是被禁止的。这导致本工业要提出新的解决方案来解决这个问题。
本发明的目的在于提供一种高效抗微生物组合物，其具有改善的皮肤相容性且对用户友好。发明人发现，将过氧化氢和N-酰化氨基酸和/或肽进行组合，优选与具有酸性pH的N-酰化氨基酸和/或肽进行组合，会得到一种温和但高效的消毒组合物。
WO 92/21318描述了一种由谷类蛋白水解产物衍生得到的氨基酸的N-酰基衍生物及其盐，以及含有所述衍生物或其盐的化妆组合物和清洁组合物。
EP 1 221 313和WO 03/039496描述了具有水合和防腐性质同时具有去屑和/或除臭性质的清洁组合物或化妆组合物。EP 1 221 313中的组合物包含十一烯酰基谷氨酸盐和/或小麦和/或稻米蛋白质的十一烯酰基水解产物；WO03/039496中的组合物包含辛酰基谷氨酸盐和/或小麦和/或稻米蛋白质的辛酰基水解产物。因为上述盐还能够起到防腐和水合作用，所以组合物不需添加额外的防腐剂或水合剂，或者至多含有本身无效的额外防腐剂或水合物的浓缩液。这些组合物未被描述用于消毒皮肤(即瞬间杀死致病性微生物)，并且也不能在较短接触时间内提供足够的杀菌力，从而不能得到可接受的皮肤消毒组合物
US2006/0024339提供了一种用于处理与皮肤病病症相关的皮肤发红的方法，所述方法通常包括，对患者的皮肤施用含有枸杞浆果提取物的药学组合物。用在这些方法中的药学组合物可以进一步包含至少一种羧酸。可选地，组合物可以含有各种其它组分，其中之一是至少一种氨基酸或过氧化氢。有用的氨基酸可以是N-乙酰基半胱氨酸。然而，未公开过氧化氢和N-乙酰基半胱氨酸的组合也未提及这种组合物具有消毒或杀菌能力。
Protelan ENS(Zschimmer & Schwarz Italiana S.p.A.)的小册子中公开了月桂酰基谷氨酸盐在Emulsifying Natural System(Protelan ENS)中的应用。Protelan ENS是硬脂酸甘油酯、鲸蜡硬脂醇、硬脂酸和月桂酰谷氨酸钠的共混物。在一系列稳定性和相容性测试中，水相中含有5％过氧化氢，油相中含有20％Protelan ENS的乳液为稳定的乳状物。
现有技术未描述如本文所述具有较高的消毒能力的组合物。业已发现过氧化氢和N-酰基化氨基酸各自具有较低的消毒能力，甚至在相对较高的浓度下也具有较低的消毒能力。然而仅仅将过氧化氢与N-酰基化氨基酸在水性体系中组合以后，就实现令人惊讶的协同作用。这种协同作用非常显著，而且从这两种成分的性能单独来看这种协同作用是完全出乎意料的。
因而，本发明提供了一种用于消毒皮肤的组合物，所述组合物包含在0.1-10％(w/w)范围内、优选在0.2-6％范围内的过氧化氢以及在0.1-20％(w/w)范围内、优选在0.1-10％范围内、更优选在0.2-8％范围内、最优选在0.2-5％(w/w)范围内的N-酰基化氨基酸和/或肽。
根据本发明，术语“N-酰基化氨基酸和/或肽”指这样的肽和/或游离氨基酸或其盐，其中所述游离氨基酸和/或所述肽中的至少50％的氨基被酰基化。优选地，所有氨基被酰基化。氨基酸可以是单一的氨基酸或者可以是可通过适当蛋白质底物的水解获得的氨基酸的混合物。在后种情况下，可能存在短链肽，通常含有平均分子量小于约4000道尔顿、优选小于约2000道尔顿的肽。
根据本发明所用N-酰基化肽和/或N-酰基化氨基酸优选具有以下式I的结构或为其盐：
R-CO-N(H)-(CH2)n-C(R’)-CO-X (I)
式I中，R-CO-表示酰基，其中R是饱和的或不饱和的直链或支链C5-C21基团，
n是0、1或2，
R’表示氨基酸侧链，
X是OH或式II基团：
[NH-CH(R’)-CO-]m NH-C(R’)-CO(OH) (II)
式II中，m在0到如下数值的范围内：式II化合物表示平均分子量在约100至约3900道尔顿范围内、优选在约100至约1900道尔顿范围内、更优选在约100至约1300道尔顿范围内、最优选在约100至约700道尔顿范围内的肽。
合适的盐指如下的盐：其中离解的羧酸基团被属于碱金属和碱土金属、氨、其它金属(诸如铅、铁、铝、锰、铜、锌)阳离子中和的盐；或其中离解的羧酸基团被有机碱中和的盐，所述有机碱诸如为精氨酸、赖氨酸、一乙醇胺、二乙醇胺、三乙醇胺、鸟氨酸、组氨酸、吗啉或胆碱。上述中和阳离子可以与彼此组合使用。
优选地，酰基中的R片段是C6-C20基团。更优选是其直链变体(饱和的以及不饱和的)。尤其优选的酰基是辛酰基、壬酰基、癸酰基、十一烷酰基、十一烯酰基、十二烷酰基(月桂酰基)、十三烷酰基、十四烷酰基(肉豆蔻酰基)、十六烷酰基(棕榈酰基)、十八烷酰基(硬脂酰基)、油酰基及其混合物。
当X是OH时，式I化合物表示氨基酸。根据本发明，术语“氨基酸”指α-氨基酸、β-氨基酸、γ-氨基酸，即n为0、1或2，但优选为α-氨基酸(n为0)。
R’表示存在于天然生蛋白氨基酸中的氨基酸侧链；或与那些存在于天然生蛋白氨基酸中的侧链相比通过如下而被修饰的侧链：将侧链中的氢原子用羟基、甲基、乙基或其它适当基团取代。
生蛋白氨基酸是通过DNA编码的氨基酸。被修饰氨基酸的实例是羟基脯氨酸，其例如存在于胶原质中。
对于式I的N-酰基化化合物(其中X是OH)而言，优选的氨基酸前体选自极性氨基酸，诸如谷氨酸、天冬氨酸、谷氨酰胺、天冬酰胺、赖氨酸、精氨酸、组氨酸、脯氨酸、苏氨酸、丝氨酸。优选的氨基酸是谷氨酸、天冬氨酸、赖氨酸。
在X是式II化合物的情况下，当m为0时X表示氨基酸单元，或者当m≥1时X表示肽。对于X而言，数值m通常可以在1-18的范围内，从而表示分子量在约200至约1900道尔顿范围的肽。
对于式I的N-酰基化化合物而言，优选的肽和/或氨基酸前体是蛋白质水解产物。蛋白质水解产物是蛋白质底物的降解产物，其通常可以通过蛋白质底物的酸性水解、碱性水解和/或酶水解而得到，其具有100至2000、优选100至1400、更具体100至800的平均分子量。最优选地，蛋白质底物主要水解成个体构成的氨基酸，优选地个体氨基酸占蛋白质水解产物的至少50％。
适当的蛋白质底物例如为植物蛋白，诸如小麦蛋白、稻米蛋白、大豆蛋白、向日葵蛋白、玉米蛋白、豌豆蛋白、杏仁蛋白和土豆蛋白；动物蛋白，如牛奶蛋白、凝胶蛋白、胶原质蛋白、角蛋白；微生物蛋白，如海藻蛋白、酵母蛋白或真菌蛋白。
可以根据蛋白质底物的氨基酸组成对其进行选择。优选地，蛋白质底物具有较高水平的谷氨酸/谷氨酰胺残基，这导致蛋白质水解产物具有较高的谷氨酸含量。这种优选蛋白质底物的实例是小麦蛋白。
根据式I的化合物方便地通过如下获得：采用式RCOOH脂肪酸(R如上所定义)的羧酸活化衍生物通过本领域已知标准方法对上述氨基酸和/肽前体进行N-酰基化。上述衍生物例如为这些酸的对称酸酐或酰卤。
所提及的N-酰基化氨基酸及其盐例如为N-酰基谷氨酸盐，诸如椰酰基谷氨酸一钠、月桂酰基谷氨酸一钠、C14-C20烷基谷氨酸二钠，所述C14-C20烷基基团由氢化牛脂衍生得到，其由Ajinomoto分别以商品名″Acylglutamate CS-11″、″Acylglutamate LS-11″和″Acylglu-tamate HS-21″销售。酰基谷氨酸盐的实例还包括由Clariant以Hostapon CCG/CLG/KCG商品名销售的椰酰基谷氨酸钠和月桂酰基谷氨酸钠以及Zschimmer &Schwarz的Protelan AG 8(辛酰基谷氨酸盐)、Protelan AGL 95(月桂基谷氨酸钠)和Protelan AGL 5/C(椰酰基谷氨酸钠)。
还可以列出N-酰基赖氨酸，诸如由Ajinomoto以商品名“AmihopeLL”销售的月桂酰基赖氨酸。
所提及的N-酰基化水解蛋白质可以是由胶原质或角蛋白的全部或部分衍生得到的那些，诸如由SEPPIC公司以商品名″Proteol B 30″和″LipacidePK″销售的月桂酰基胶原质钠和棕榈酰基角蛋白；或者是由小麦衍生得到的那些，诸如由Zschimmer & Schwarz以“Protelan AG 11”销售的十一烯酰基水解小麦蛋白钾。
本文所述组合物可以包含两种或多种上述N-酰基化产物的混合物。
本文所述组合物的pH优选在2-6的范围内，更优选在3-6的范围内，最优选在3.5-5的范围内。
本文所述组合物可以进一步包含表面活性剂，诸如两亲性表面活性剂、阴离子表面活性剂、阳离子表面活性剂和/或非离子表面活性剂。
适当的两亲表面活性剂包括两亲性烷基多糖苷、烷基甜菜碱、烷基酰胺丙基甜菜碱、烷基酰胺丙基甜菜碱酰胺、烷基磺基甜菜碱、氧化胺、两亲性羧基乙酸酯、两亲性羧基二乙酸酯、两亲性羧基丙酸酯、两亲性羧基二丙酸酯及/或其衍生物。
适当的阴离子表面活性剂包括烷基硫酸盐、烷基醚硫酸盐、酰胺基/酰胺基醚硫酸盐、烷基半磺基琥珀酸酯、烷基磺基琥珀酸酯、烷基醚半磺基琥珀酸酯、烷基醚磺基琥珀酸酯、酰氨基半磺基琥珀酸酯、酰氨基磺基琥珀酸酯、十二烷基苯磺酸、烷基/烷基醚磺基乙酸酯、磺酸化的和/或硫酸化的有机分子的盐(例如α-烯烃磺酸盐)、烷基/烷基醚羧酸盐、烷基膦酸盐、磷酸的酯、酰基羟乙基磺酸及其盐。优选的阴离子表面活性剂可以选自以钾盐、钠盐、铵盐、锌盐、铝盐或三乙醇胺盐形式的磷酸酯、烷基膦酸盐、烷基硫酸盐、烷基醚硫酸盐、烷基磺基琥珀酸酯、烷基醚磺基琥珀酸酯。甚至更优选的是锌盐形式或铝盐形式。
适当的阳离子表面活性剂包括皮肤调节阳离子聚合物，优选选自聚季铵盐型表面活性剂，诸如包括甲基丙烯酰胺丙基三甲基氯化铵、二烯丙基二甲基氯化铵或甲基丙稀酰氧乙基三甲基甲硫酸铵。
适当的非离子表面活性剂包括酰胺、乙氧基化的和非乙氧基化的脂肪胺、乙氧基化的壬基苯酚、APG(烷基多糖苷)、AEG(烷基乙氧基糖苷)、脂肪酸与丙三醇和/或乙氧基化的以及非乙氧基化的糖的酯/醚、乙氧基化的/丙氧基化的酯以及非乙氧基化的/丙氧基化的酯、乙氧基化的/丙氧基化的脂肪醇以及非乙氧基化的/丙氧基化的脂肪醇。
本文所述组合物可以进一步包含羧酸或其盐，所述羧酸优选选自柠檬酸、乙醇酸、乳酸、苯甲酸、水杨酸和2-呋喃羧酸。
本文所述组合物可以进一步包含对于在皮肤上使用的组合物有益的成分。例如，所述组合物可以包含润肤剂、稳定剂、珠光剂、增稠剂、防腐剂、着色剂或染料、以及香料。
润肤剂可以包括丙三醇、甘油酯、聚丙三醇、芦荟(aloe vera)、维生素E、山梨醇、尿囊素、阳离子表面活性剂、聚合物、蓖麻油、羊毛脂及其衍生物和鲸蜡醇。
可以通过本领域普通技术人员已知的方法使组合物增稠，例如通过添加氯化钠或者氯化钠与特定类型表面活性剂(诸如月桂基醚硫酸钠或甜菜碱)的组合；或者通过添加以(羟基)纤维素为基体或者以(交联)聚合物为基体的增稠剂。优选地，组合物通过使用以(羟基)纤维素为基体或者以(交联)聚合物为基体的增稠剂进行增稠，所述增稠剂例如为Klucel types(Hercules Chemicals)、Natrosol types(Hercules Chemicals)、Carbopol types(Noveon)或Zschimmer & Schwarz的Oxetal VD 92。通过这些方法并且调节pH范围，可以达到在整个范围内的粘度水平。
本发明的组合物可以通过使用与过氧化氢相容的防腐剂来保存，所述防腐剂诸如为各种类型的对羟基苯甲酸酯(parabens)、苄醇、苯甲酸、苯甲酸钾、水杨酸、水杨酸钾等。
本发明的组合物还可以包含螯合剂，诸如选自乙二胺四乙酸(EDTA)、二亚乙基三胺五乙酸(DTPA)、N-(羟乙基)-乙二胺三乙酸(HEDTA)、次氮基三乙酸(NTA)、2-羟乙基亚氨基二乙酸(HEIDA)及其盐的的阳离子螯合剂，更优选选自N-乙酰苯胺、乙二胺二琥珀酸三钠、具有1-5个膦酸基团的膦酸衍生物，例如Dequest膦酸(Solutia)、1-羟基亚乙基-1，1-二膦酸(HEDP)、氨基三(亚甲基膦酸)、二亚乙基三胺五(亚甲基膦酸)、2-羟乙基亚氨基二(亚甲基膦酸)和乙二胺四(亚甲基膦酸)。
本文所述组合物可以为水性溶液或乳液形式，诸如为洗液、泡沫、液体肥皂、喷雾、啫哩、乳膏等等，或者可以为浸渍擦拭(impregnatedwipe)形式。当组合物含有油相和水相时，组合物不包含浓度为20％(w/w)的自乳化基质Protelan ENS。
在一个实施方式中，组合物是水性溶液，其可以具有各种粘度。
在优选的实施方式中，以泡沫形式应用组合物，从而提高接触面积和接触时间，并且避免所需剂量从手中泄露或滴落(如在使用喷雾制剂时可能的情形)。在本文所述组合物中使用N-酰基化氨基酸为组合物提供发泡能力。
优选地，本文所述组合物能够提供适当的消毒水平，而不会对皮肤或粘膜造成刺激。这种组合物无刺激，这是因为其中含有大量与皮肤相容的N-酰基化氨基酸/蛋白质水解产物、温和的表面活性剂以及低浓度的其它温和添加剂，它们可以如以上所述进行使用。这种组合物具有广谱活性，其活性程度相对于单个成分的杀菌活性是出乎意料的。具体地，这种组合物具有杀细菌活性、杀真菌活性和杀病毒活性。本发明组合物中的各成分之间具有协同作用，结果获得非常适于在皮肤上使用的有效消毒剂。
因而，本文所述组合物有利于用在消毒皮肤或粘膜具有一定作用的所有应用中。这种组合物可以用作日常使用的杀菌组合物，诸如洗手肥皂、杀菌型沐浴啫哩、浸渍擦拭巾，或者用作私密护理溶液。这种组合物可以用于预防、调节或治愈由微生物引起的皮肤失调症或感染，诸如但不限于痤疮、脂溢性皮炎、毛囊炎、融合性网状乳头瘤病和银屑病皮损以及汗脚。
实施例
根据本发明制备数种杀生皮肤组合物，并将其与现有技术中已知的杀生皮肤组合物(诸如过氧化氢和甜菜碱)进行比较。使用各种组分的商购浓缩母液在蒸馏水中制备组合物。
所用产品的说明
Protelan AG 8 辛酰基谷氨酸二钠(Zschimmer & Schwarz)
Protelan AG 11 十一烯酰基水解小麦蛋白钾(Zschimmer &
Schwarz)
Protelan AGL 95 月桂酰基谷氨酸钠(Zschimmer & Schwarz)
Monafax 1214 脂族膦酸酯(Uniqema)
Texapon NSO 月桂基醚硫酸钠(Cognis)
Zetesol NL U 月桂基醚硫酸钠(Zschimmer & Schwarz)
Zetesol Zn 椰油醇聚醚硫酸锌(Zschimmer & Schwarz)
Tego Betaine F 椰油酰胺丙基甜菜碱(Degussa)
Mackam CB 818 椰油酰胺丙基甜菜碱(McIntyre)
Octaquest 乙二胺二琥珀酸三钠
采用符合化学消毒剂和杀菌剂的欧洲标准EN1276(EN1276：用于评估在食品、工业、家庭和公共区域内使用的化学消毒剂和杀菌剂的杀菌活性的定量悬浮测试：测试方法和要求)的受控杀菌悬浮测试对本发明组合物的杀生活性进行测试。将1ml的测试悬浮液(含有约108cfu个测试微生物/ml)加入8ml待测组合物中，然后加入1ml Milli-Q水。通过添加牛白蛋白血清(分别添加0.3％和3.0％)来模拟清洁环境和肮脏环境。在接触时间为1分钟、3分钟和5分钟后，测定存活细菌的数量。EN1276标准规定接触5分钟后存活细胞数的对数下降值为5。
结果列在表1-3中。
表1
组合物
组分 1 2 3 4 5 6 7 8 9
过氧化氢 3％ 3％ 3％ 3％ 3％ 3％ 3％ 3％ 3％
Protelan AG 8 1.95％ 1.95％ 1.95％ 1.95％ 1.95％
Protelan AGL 95 1.95％
Protelan AG 11 0.72％ 0.72％ 0.72％
Tego Betain F50 1.52％ 1.52％ 1.52％ 1.52％ 1.52％ 1.52％ 1.52％
Zetesol Zn 1.25％ 1.25％ 1.25％
Monafax 1214 0.8％
pH(乳酸) 4 4 4 4 4 4 4 4 4
对数下降值
S.aureus
3min. ＞6.6 4 ＞6.6 ＞6.6 2.2 1 ＞6.6 ＞6.6 5.2
5min. ＞6.6 5 ＞6.6 ＞6.6 4 3 ＞6.6 ＞6.6 ＞6.6
S.thyphimurium
3min ＞6 4 ＞6 ＞6 1 nc* ＞6 ＞6 4.6
E.coli
3min. ＞6 4.6 ＞6 ＞6 3 2 ＞6 ＞6 4.8
*nc＝不可计
表2
组合物
组分 10 11 12 13 14 15 16 17
过氧化氢 2.5％ 2.5％ 2.5％ 2.5％ 2.5％ 2.5％ 2.5％ 2.75％
Protelan AG 8 1.95％ 1.95％ 1.95％ 1.95％ 1.95％ 1.95％ 1.95％ 1.95％
Protelan AG 11 0.72％ 0.72％ 0.72％
Tego Betain F50 1.9％ 1.9％ 1.9％ 1.9％ 1.9％ 1.9％ 1.9％ 1.9％
Zetesol Zn 2.5％ 1％ 1％ 1％ 1％ 2.25％
Texapon NSO 0.84％ 1.12％
Monafax 1214 0.64％ 0.64％ 0.64％
EDTA 0.1％ 0.15％
Octaquest 0.05％ 0.05％
苯甲酸Na 0.15％ 0.15％ 0.15％
水杨酸Na 0.1％ 0.1％
呋喃羧酸 0.05％
NaCl 1％
pH(柠檬酸) 4 4 4 4.5 4 4 4.5 5.5
对数下降值
S.aureus
3min. 4.4 5.4 ＞6.6 5.6 4.8 5.6 ＞6.6 ＞6.6
5min. ＞6.6 ＞6.6 ＞6.6 ＞6.6 ＞6.6 ＞6.6 ＞6.6 ＞6.6
表3
组合物
组分 18 19 20 21 22 23 24 25
过氧化氢 2％ 2.5％ 2.5％ 2.5％ 2％ 2％ 2％ 2％
Protelan AG 8 2.35％ 1.95％ 1.95％ 1.95％ 3.12％ 1.95％ 3.12％
Mackam CB 818 1％ 2％ 1.9％ 1.9％ 1.9％ 1.9％ 1.9％
Zetesol NL U 3.35％ 3.35％ 4.20％ 4.20％ 3.35％ 3.35％ 3.35％ 3.35％
甘油 1％ 1％ 2％ 2％ 1％ 1％ 1％ 1％
苯甲酸Na 0.15％ 0.15％
水杨酸Na 0.1％ 0.1％
pH(乳酸) 4 4 3.5 3.5 4 4 4 4.5
对数下降值
E.coli 1min. ＞5 ＞5 ＞5 ＞5 1.1 ＞6 ＞6 ＞6
S.aureus 1min. ＞5 ＞5 ＞5 ＞5 2.3 ＞6 ＞6 ＞5
组合物1-4、7-21和23-25是根据本发明的组合物。这些组合物具有较高的杀菌功效，尤其在组合物被阴离子表面活性剂或两亲性表面活性剂进一步完善的情况下。组合物18-21甚至在接触时间仅为1分钟的情况下通过了在模拟清洁条件下以及肮脏条件下对所有测试微生物(Escherichiacoli、Pseudomonas aeruginosa、Staphylococcus aureus和Enterococcushirae)的标准(对数下降值＞5)。
组合物5、6和22是未根据本发明的组合物，其杀菌活性明显较低或没有杀菌活性。这些实施例清楚地表明，过氧化氢本身不具有足够的消毒能力，而含有过氧化氢和N-酰基化氨基酸的组合物的高效令人惊讶。
为了进一步表明组合物中其它表面活性剂的影响，制备了组合物3、4和24。这些组合物未含有椰油酰胺丙基甜菜碱(具有轻微杀菌特性的表面活性剂)，但通过了EN1276标准。组合物22和24的比较结果进一步表明，椰油酰胺丙基甜菜碱对组合物功效的影响实际上并不存在。
组合物18-21还通过了卫生洗手(hygienic hand washing)的欧洲标准EN1499，其中接触时间仅为30秒。不含过氧化氢或不含N-酰基化氨基酸的组合物没有通过该测试，甚至在接触时间为60秒的情况下也没有通过。
令人惊讶地，本文所述组合物还具有杀病毒功效。组合物18-21在受控杀病毒悬浮测试中杀死了血液传染包膜病毒(enveloped blood bornevirus)(基于模型病毒牛病毒性腹泻病毒(BVDV)和牛痘病毒)，其中接触时间仅为30秒。根据被接受的德国标准(Robert Koch Institute，Deutsche Gesellschaft für Hygien und Medizin)，规定抗BVDV和牛痘二者的功效对所有血液传染包膜病毒(诸如HIV、HCV、HBV、人流感、H5N1和SARS，Dr J.Steinmann在Mikrolab GmbH测试)起作用。
在受控皮肤过敏测试中对组合物18-21进行了测试，其中测试48-72小时，对具有不同皮肤状态的50人进行测试：25人具有正常的健康皮肤，5人患有湿疹，1人具有过敏皮肤，19人具有敏感皮肤。将组合物18-21与十二烷基硫酸钠(SDS)在水中的1％稀释液相比，并在红斑、裂口和起皮(scaling)方面进行评估。SDS溶液在12个案例中具有明显的刺激。采用组合物18-21处理48-72小时后，没有一名研究对象的皮肤上出现任何发红或刺激。这些测试结果清楚地表明，广谱高效杀菌组合物18-21对皮肤令人惊讶地温和。
重点注意的是，杀菌活性不是本文所述杀菌皮肤组合物中唯一重要的特性。还发现，这种组合物对皮肤异常友好，从而使用户具有柔软、被充分护理的用后感觉。为了使组合物有效，皮肤感觉、去污除脂性、起泡效果(lathering effect)、对皮肤的保湿性、不发粘以及皮肤的用后感觉连同杀菌作用一起都应进行考虑。
Claims (27)
1.一种用于皮肤消毒的组合物，所述组合物包含浓度为0.1-10％(w/w)的过氧化氢以及在0.1-20％(w/w)范围内的含有具有6-20个碳原子的酰基基团的N-酰基化氨基酸，或其盐，其中，当所述组合物包含油相和水相时，所述组合物不包含浓度为20％的自乳化基质普特兰ENS，其中，所述N-酰基化氨基酸是N-酰基化谷氨酸。
2.如权利要求1所述的组合物，所述组合物为水性溶液。
3.如权利要求1所述的组合物，其中，所述过氧化氢的浓度为0.2-6％(w/w)。
4.如权利要求1所述的组合物，其中，所述N-酰基化氨基酸，或其盐的浓度在0.1至10％(w/w)的范围内。
5.如权利要求1所述的组合物，其中，所述N-酰基化氨基酸，或其盐的浓度在0.2至8％(w/w)的范围内。
6.如权利要求1所述的组合物，其中，所述N-酰基化氨基酸，或其盐的浓度在0.2至5％(w/w)的范围内。
7.如权利要求1-2中任意一项所述的组合物，所述组合物的pH在2-6的范围内。
8.如权利要求7所述的组合物，其中所述组合物的pH在3-6的范围内。
9.如权利要求7所述的组合物，其中所述组合物的pH在3.5-5的范围内。
10.如权利要求1所述的组合物，其中，所述酰基基团是饱和的或不饱和的直链酰基基团。
11.如权利要求1所述的组合物，其中所述N-酰基化氨基酸含有具有8-18个碳原子的酰基基团。
12.如权利要求1所述的组合物，进一步包含两亲性表面活性剂、阴离子表面活性剂、阳离子表面活性剂和/或非离子表面活性剂。
13.如权利要求12所述的组合物，其中，所述两亲性表面活性剂选自两亲性烷基多糖苷、烷基甜菜碱、烷基酰胺丙基甜菜碱、烷基酰胺丙基甜菜碱酰胺、烷基磺基甜菜碱、氧化胺、两亲性羧基乙酸酯、两亲性羧基二乙酸酯、两亲性羧基丙酸酯、两亲性羧基二丙酸酯。
14.如权利要求12所述的组合物，其中，所述阴离子表面活性剂选自烷基硫酸盐、烷基醚硫酸盐、酰胺基/酰胺基醚硫酸盐、烷基半磺基琥珀酸酯、烷基磺基琥珀酸酯、烷基醚半磺基琥珀酸酯、烷基醚磺基琥珀酸酯、酰氨基半磺基琥珀酸酯、酰氨基磺基琥珀酸酯、十二烷基苯磺酸、烷基/烷基醚磺基乙酸酯、磺酸化的和/或硫酸化的有机分子的盐、烷基/烷基醚羧酸盐、烷基膦酸盐、磷酸的酯、酰基羟乙基磺酸及其盐。
15.如权利要求12所述的组合物，其中，所述阳离子表面活性剂选自皮肤调节阳离子聚合物。
16.如权利要求15所述的组合物，其中，所述阳离子表面活性剂选自聚季铵盐型表面活性剂。
17.如权利要求12所述的组合物，其中，所述非离子表面活性剂选自酰胺、乙氧基化的和非乙氧基化的脂肪胺、乙氧基化的壬基苯酚、APG烷基多糖苷、AEG烷基乙氧基糖苷、脂肪酸与丙三醇和/或乙氧基化的和非乙氧基化的糖的酯/醚、乙氧基化的/丙氧基化的酯以及非乙氧基化的/丙氧基化的酯、乙氧基化的/丙氧基化的脂肪醇以及非乙氧基化的/丙氧基化的脂肪醇。
18.如权利要求1所述的组合物，进一步包含羧酸或其盐。
19.如权利要求18所述的组合物，其中所述羧酸选自柠檬酸、乙醇酸、乳酸、苯甲酸、水杨酸和2-呋喃羧酸。
20.如权利要求1所述的组合物，进一步包含润肤剂。
21.如权利要求20所述的组合物，其中，所述润肤剂选自丙三醇、甘油酯、芦荟、维生素E、山梨醇、尿囊素、聚合物、蓖麻油、羊毛脂及其衍生物和鲸蜡醇。
22.如权利要求21所述的组合物，其中，所述润肤剂选自聚丙三醇。
23.如权利要求1所述的组合物，进一步包含稳定剂、增稠剂、防腐剂、着色剂、以及香料。
24.如权利要求23所述的组合物，进一步包含珠光剂和染料。
25.权利要求1-24中任意一项所述组合物在制造用于消毒皮肤或粘膜的产品中的用途。
26.权利要求1-24中任意一项所述组合物在制造作为日常使用的杀菌组合物的产品中的用途。
27.如权利要求1-24中任意一项所述的组合物在制造用于预防、调节或非治疗目的治愈皮肤感染或皮肤失调症的产品中的用途。
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| EP06126044.4 | 2006-12-13 | ||
| PCT/EP2007/063831 WO2008071746A1 (en) | 2006-12-13 | 2007-12-12 | Mild composition for skin disinfection |
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| CN101553202A CN101553202A (zh) | 2009-10-07 |
| CN101553202B true CN101553202B (zh) | 2015-07-22 |
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| EP (1) | EP2101720B1 (zh) |
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| CN (1) | CN101553202B (zh) |
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| CA (1) | CA2671471C (zh) |
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| HK (1) | HK1136966A1 (zh) |
| PL (1) | PL2101720T3 (zh) |
| RU (1) | RU2441644C2 (zh) |
| WO (1) | WO2008071746A1 (zh) |
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| US8383164B2 (en) * | 2009-06-29 | 2013-02-26 | Innovasource Llc | Antiviral composition and method for using the same |
| JP5508053B2 (ja) * | 2010-02-18 | 2014-05-28 | 旭化成ケミカルズ株式会社 | 殺菌剤 |
| CN103068225B (zh) * | 2010-06-07 | 2015-12-16 | 斯蒂潘公司 | 可稀释的杀生物组合物和使用方法 |
| US20130089533A1 (en) | 2011-10-05 | 2013-04-11 | Arkema Inc. | Disinfectant compositions with hydrogen peroxide |
| US20130089621A1 (en) | 2011-10-05 | 2013-04-11 | Arkema Inc. | Disinfectant compositions with hydrogen peroxide |
| EA022773B1 (ru) * | 2012-05-24 | 2016-02-29 | Ооо "Научно-Производственный Центр Химмедсинтез" | Дезинфицирующий состав |
| FR2992859B1 (fr) * | 2012-07-09 | 2014-10-03 | Fabre Pierre Dermo Cosmetique | Utilisation de coceth sulfate de zinc comme agent antibacterien vis a vis de propionibacterium acnes |
| CN103520022B (zh) * | 2013-10-21 | 2015-12-23 | 广州立白企业集团有限公司 | 一种抑菌洗手液及其制备方法 |
| JP6162579B2 (ja) * | 2013-11-14 | 2017-07-12 | 雪印メグミルク株式会社 | 新規な静菌または抗菌剤 |
| BR112017016729B1 (pt) * | 2015-02-05 | 2022-09-13 | Hygienix Bv | Método para desinfetar uma superfície e composição adequada para uso no mesmo |
| CA2991917A1 (en) | 2015-07-17 | 2017-01-26 | Colgate-Palmolive Company | Oral care compositions |
| RU2636496C1 (ru) * | 2016-08-18 | 2017-11-23 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Московский технологический университет" | Противомикробное универсальное мыло на основе пероксида водорода с высокой стабильностью |
| RU2669343C2 (ru) * | 2016-12-14 | 2018-10-10 | федеральное государственное бюджетное образовательное учреждение высшего образования "Самарский государственный технический университет" | Дезинфицирующая композиция |
| EP3582618A4 (en) * | 2017-02-17 | 2020-12-30 | Diversey, Inc. | PEROXIDE-BASED DISINFECTANT SOLUTIONS WITH INORGANIC SALT |
| CN108477209B (zh) * | 2018-05-30 | 2021-01-15 | 军事科学院系统工程研究院卫勤保障技术研究所 | 一种消毒液及其制备方法 |
| AU2019417293A1 (en) * | 2018-12-28 | 2021-05-20 | Diversey, Inc. | Synergistic disinfectant compositions having enhanced antimicrobial efficacy and stability, and methods of using the same |
| WO2020167933A1 (en) | 2019-02-12 | 2020-08-20 | Alden Medical, Llc | Alcohol-free hydrogen peroxide disinfectant compositions and methods of use thereof |
| SE544655C2 (en) * | 2020-11-18 | 2022-10-04 | Lantmaennen Oats Ab | Anti-microbial skin-care composition comprising beta-glucan, hydrogen peroxide and lactic acid |
| CN114287451B (zh) * | 2021-12-31 | 2022-12-27 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种天然植物改性抗菌液的制备方法及其产品 |
| JP7315263B1 (ja) | 2022-06-17 | 2023-07-26 | 株式会社ニイタカ | ウイルス不活化組成物、消毒剤、洗浄剤、及び、衛生資材 |
| WO2024074910A1 (en) * | 2022-10-07 | 2024-04-11 | 3M Innovative Properties Company | Biocidal composition |
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| DE19815972C1 (de) | 1998-04-09 | 1999-09-30 | Goldwell Gmbh | Fixiermittel für Dauerwellen |
| US6071541A (en) | 1998-07-31 | 2000-06-06 | Murad; Howard | Pharmaceutical compositions and methods for managing skin conditions |
| EP1129701A1 (de) | 2000-02-29 | 2001-09-05 | Primacare S.A. | Kosmetische Zubereitungen enthaltend einen Chemolumineszenz-Farbstoff |
| EP1221313A3 (en) | 2001-01-09 | 2003-11-26 | Zschimmer & Schwarz Italiana S.p.A. | Salts of undecylenoyl glutamate or of undecylenoyl hydrolyzate of wheat or rice proteins in detergent or cosmetic compositions |
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- 2007-12-12 AU AU2007331481A patent/AU2007331481B2/en not_active Ceased
- 2007-12-12 ES ES07857493T patent/ES2570599T3/es active Active
- 2007-12-12 RU RU2009121450/15A patent/RU2441644C2/ru active
- 2007-12-12 CN CN200780045590.8A patent/CN101553202B/zh not_active Expired - Fee Related
- 2007-12-12 DK DK07857493.6T patent/DK2101720T3/en active
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- 2007-12-12 EP EP07857493.6A patent/EP2101720B1/en active Active
- 2007-12-12 PL PL07857493.6T patent/PL2101720T3/pl unknown
- 2007-12-12 WO PCT/EP2007/063831 patent/WO2008071746A1/en active Application Filing
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| US5458881A (en) * | 1991-06-03 | 1995-10-17 | Givaudan-Lavirotte | N-acylated derivatives of mixtures of amino acids derived from hydrolysates of cereal proteins and their applications |
| CN1268162A (zh) * | 1997-07-09 | 2000-09-27 | 普罗格特-甘布尔公司 | 包含氧化还原酶的清洗组合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2101720B1 (en) | 2016-03-23 |
| RU2441644C2 (ru) | 2012-02-10 |
| BRPI0720201B1 (pt) | 2016-03-29 |
| AU2007331481B2 (en) | 2012-12-20 |
| RU2009121450A (ru) | 2011-01-20 |
| DK2101720T3 (en) | 2016-06-13 |
| CA2671471C (en) | 2015-11-03 |
| PL2101720T3 (pl) | 2016-09-30 |
| AU2007331481A1 (en) | 2008-06-19 |
| US8236357B2 (en) | 2012-08-07 |
| ES2570599T3 (es) | 2016-05-19 |
| JP5438518B2 (ja) | 2014-03-12 |
| CN101553202A (zh) | 2009-10-07 |
| BRPI0720201A2 (pt) | 2013-12-31 |
| US20100028458A1 (en) | 2010-02-04 |
| WO2008071746A1 (en) | 2008-06-19 |
| EP2101720A1 (en) | 2009-09-23 |
| HK1136966A1 (zh) | 2010-07-16 |
| JP2010513244A (ja) | 2010-04-30 |
| CA2671471A1 (en) | 2008-06-19 |
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