CN116472022A - 稳定的抗微生物制剂浓缩物 - Google Patents
稳定的抗微生物制剂浓缩物 Download PDFInfo
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- CN116472022A CN116472022A CN202080106752.XA CN202080106752A CN116472022A CN 116472022 A CN116472022 A CN 116472022A CN 202080106752 A CN202080106752 A CN 202080106752A CN 116472022 A CN116472022 A CN 116472022A
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- Prior art keywords
- composition
- glycol
- hydroxyacetophenone
- antimicrobial
- weight
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- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 125000001453 quaternary ammonium group Chemical class 0.000 description 1
- 150000004023 quaternary phosphonium compounds Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- HVFAVOFILADWEZ-UHFFFAOYSA-M sodium;2-[2-(dodecanoylamino)ethyl-(2-hydroxyethyl)amino]acetate Chemical compound [Na+].CCCCCCCCCCCC(=O)NCCN(CCO)CC([O-])=O HVFAVOFILADWEZ-UHFFFAOYSA-M 0.000 description 1
- CAVXVRQDZKMZDB-UHFFFAOYSA-M sodium;2-[dodecanoyl(methyl)amino]ethanesulfonate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CCS([O-])(=O)=O CAVXVRQDZKMZDB-UHFFFAOYSA-M 0.000 description 1
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- CXVGEDCSTKKODG-UHFFFAOYSA-N sulisobenzone Chemical compound C1=C(S(O)(=O)=O)C(OC)=CC(O)=C1C(=O)C1=CC=CC=C1 CXVGEDCSTKKODG-UHFFFAOYSA-N 0.000 description 1
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- 239000003760 tallow Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 230000000930 thermomechanical effect Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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- ICUTUKXCWQYESQ-UHFFFAOYSA-N triclocarban Chemical class C1=CC(Cl)=CC=C1NC(=O)NC1=CC=C(Cl)C(Cl)=C1 ICUTUKXCWQYESQ-UHFFFAOYSA-N 0.000 description 1
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- 229940087291 tridecyl alcohol Drugs 0.000 description 1
- AISMNBXOJRHCIA-UHFFFAOYSA-N trimethylazanium;bromide Chemical compound Br.CN(C)C AISMNBXOJRHCIA-UHFFFAOYSA-N 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
- QUTYHQJYVDNJJA-UHFFFAOYSA-K trisilver;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Ag+].[Ag+].[Ag+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QUTYHQJYVDNJJA-UHFFFAOYSA-K 0.000 description 1
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/22—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing ingredients stabilising the active ingredients
-
- 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
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Abstract
描述了提供稳定的抗微生物制剂浓缩物的组合物。所述组合物可以包含至少一种二醇。所述至少一种二醇可以包含具有少于六个碳的碳链的第一种二醇。在一些变化中,所述组合物可以包含非离子表面活性剂。所述组合物还可以包含羟基苯乙酮。所述羟基苯乙酮可以提供至少10重量%的所述组合物。
Description
技术领域
公开了抗微生物制剂浓缩物和抑制微生物生长的方法。更具体地,公开了包含至少一种二醇和羟基苯乙酮的抗微生物制剂浓缩物。在稀释后,抗微生物组合物浓缩物可用于或掺入到制品(诸如擦拭物)中,或者掺入到溶液、软膏剂、洗剂、霜剂、油膏、气溶胶剂、凝胶剂、混悬剂、喷雾剂、泡沫、洗涤剂等中。
背景技术
防腐剂是化妆品产品、药物产品、家庭、工业和个人护理产品中经常利用的组分,用于确保产品在货架上保持新鲜、不发生腐败,并且保持无细菌生长。特别地,由于个人护理产品可以用于直接接触皮肤或粘膜(诸如身体孔口周围的皮肤或粘膜),在所述皮肤或粘膜处可能存在物质从所述产品转移到消费者的问题,因而以每一种可能的方式减少所述产品的污染通常是良好的做法。控制微生物生长,这一需要在水基产品(诸如非离子水包油型乳剂)和预浸渍擦拭物(诸如湿擦拭物)中特别迫切。
防止微生物生长的抗微生物剂的多种选择(诸如甲醛供体或对羟基苯甲酸酯)在历史上一直存在,这些抗微生物剂非常有效,并且允许相对容易地保存个人护理产品。最近,鉴于新的法规和消费者的认知,传统抗微生物剂在个人护理产品中已经成为不太理想的组分,因而限制了用于防止某些产品中的微生物生长的选择。
尽管已经探索了替代性抗微生物剂,但每种防腐剂都有局限性。例如,一些有机酸及其衍生物已因具有抗微生物效果被使用,但是,有机酸常常具有固有的气味,因此限制了可使用而不会负面影响产品的整体嗅觉认知的浓度。另外,有机酸通常仅在酸形式时有效,因此将其用途限于具有狭窄且低pH范围的组合物,并且有机酸还具有有限的水溶性。辛基异羟肟酸还作为一种替代性抗微生物剂被探索并解决了上述一些问题(因为辛基异羟肟酸没有异味,并且在更宽的pH范围内有效),但是辛基异羟肟酸的水溶性非常有限,大约为0.14%。这种有限的水溶性阻止了辛基异羟肟酸在成分有限的组合物中以较高的百分比使用。
解决这些问题的一种抗菌成分是羟基苯乙酮。已确定羟基苯乙酮对多种微生物有效,包括难以杀死的生物体,诸如巴西放线菌(A.brasiliensis)和白色念珠菌(C.albicans)。羟基苯乙酮的功效几乎没有pH依赖性,这使得它可以有效地用于各种制剂中,并且比典型的有机酸防腐剂提供更大的制剂灵活性。除了其抗微生物的好处,羟基苯乙酮还提供其他好处,包括抗氧化和抗刺激作用。因此,仍然需要包含替代性抗微生物剂的抗微生物组合物,这些替代性抗微生物剂可以在组合物中使用以抑制产品中的微生物生长并且具有较低气味、可以在更宽的pH范围内在组合物中使用而不丧失抗微生物生长的功效,并且可以具有比现有的替代性抗微生物剂更大的水溶性。
尽管羟基苯乙酮提供了重要的益处,但是它也具有缺点,并且在掺入抗微生物制剂时存在挑战。例如,一个缺点是纯形式的羟基苯乙酮通常以结晶固体或粉末的形式产生。这需要共混设施使用人工来称量和添加羟基苯乙酮(这可能增加潜在的劳动力成本),或者使用专门的固体处理设备(这导致资本成本,并且可能需要制造设施的额外占地面积)。
此外,羟基苯乙酮的水溶性有限(22℃下为1%),这使得它很难溶解在高度含水的制剂中,诸如许多个人护理产品中使用的制剂。以有效抗微生物活性的水平完全溶解羟基苯乙酮通常需要剧烈和延长的共混时间和/或在共混期间将批料加热至高温。对于没有加热能力的制造设施,这可能会导致大大降低效率并限制产量的长批处理时间。
加速共混含有羟基苯乙酮的制剂的一个选择是将羟基苯乙酮与其他制剂成分预共混成浓缩物,所述浓缩物可能在具有更大共混/加热能力的场所外共混,然后运送到最终制造场所,在那里它可以被稀释并与其他制剂成分共混以产生最终稀释的抗微生物制剂。然而,这种方法也提供了若干挑战。因为羟基苯乙酮的水溶性有限,所以增加所述成分的浓度会使其更难溶解,并且通常会导致羟基苯乙酮从溶液中结晶出来,尤其是在低温下,诸如在运输期间可能遇到的低温。
虽然可以使用表面活性剂和溶剂来帮助提高浓缩物中羟基苯乙酮的溶解度,但是消费者越来越需要含有少量和低浓度非水成分的化妆品制剂,因为这些成分被认为不如水那样“纯净”或“天然”。此外,添加其他增溶剂会导致总制剂成本增加。对于任何浓缩物,还需要最大化共混物中羟基苯乙酮的浓度,以最小化浓缩物从浓缩物共混设施到最终生产设施的共混和运输成本。
由于这些原因,非常希望生产一种浓缩物,其包含高浓度的羟基苯乙酮,在浓缩物中具有最少量的其他成分,并且相对于羟基苯乙酮以低浓度存在。这种浓缩物共混物将为制造灵活性、资本支出、产品成本和消费者愉悦提供显著的益处。
发明内容
在本公开的一个方面,提供了一种组合物。所述组合物可以包含至少一种二醇。所述至少一种二醇可以包含具有少于六个碳的碳链的第一种二醇。所述组合物还可以包含非离子表面活性剂。所述组合物可以进一步包含羟基苯乙酮。所述羟基苯乙酮可以提供至少10重量%的组合物。
在本公开的另一个方面,提供了另一种组合物。所述组合物可以包含第一种二醇。所述第一种二醇可以包含具有少于六个碳的碳链。所述组合物还可以包含第二种二醇。所述组合物可以另外包含非离子表面活性剂。此外,所述组合物可以包含羟基苯乙酮。
在本公开的又另一方面,提供了一种组合物。所述组合物可以包含呈组合物的第一重量百分比的第一种二醇。所述组合物还可以包含呈组合物的第二重量百分比的辛酰二醇。所述第一重量百分比和所述第二重量百分比可以提供组合物的总二醇重量百分比。所述组合物还可以包含呈组合物的至少10重量%的羟基苯乙酮。所述总二醇重量百分比与所述羟基苯乙酮的量的比率大于4.0。
具体实施方式
本公开涉及可用于抑制微生物生长的组合物。本公开的组合物包含至少一种二醇和羟基苯乙酮的抗微生物成分。在优选的实施方案中,本公开的组合物可以呈浓缩物的形式,使得羟基苯乙酮大于组合物的10重量%。浓缩物组合物可以随后被稀释(例如,诸如通过用水稀释)和/或用其他功能性和非功能性成分稀释,以形成可用于多种产品的抗微生物组合物,诸如化妆品、药物、家庭、食品、工业和个人护理产品。合适的产品可以包括但不限于:香波、调理剂、皂、保湿剂、皮肤保护剂、皮肤修复剂和皮肤强化产品、洗手液、皮肤和身体清洁剂、除臭剂、防晒剂、唇香膏、唇膏、消毒剂、硬表面清洁剂、洗碗皂、洗衣液等。这些产品可以采用多种形式,包括但不限于水稀薄液体、水性溶液、凝胶、香膏、洗剂、软膏剂、混悬剂、霜剂、乳、油膏、软膏剂、糊剂、粉末、气溶胶剂、喷雾剂、雾、摩丝、乳剂、油、泡沫、洗涤剂、固体棒状物、气溶胶剂,水、油或有机硅溶液或乳剂(包括油包水型、水包油型、水包有机硅型、有机硅包水型)等。此外,如下文将进一步详细描述的,所述形式的这些产品可以连同基材使用,使得可以将溶液添加到基材上以便递送。合适的基于基材的产品包括但不限于:擦拭物、面巾纸、卫生纸、纸巾、餐巾纸、尿布、尿布裤、女性卫生产品(棉塞、衬垫)、手套、袜子、面罩或它们的组合。
在上述预想的每一种产品中,所述组合物可以被稀释并与化妆品、药物、家庭、工业和个人护理产品中所利用的多种成分一起使用。合适的成分(其中一些将在本文中进一步详细描述)可以来自广泛的类别范围,包括但不限于水性溶剂、非水性溶剂、湿润剂、润肤剂、表面活性剂、乳化剂、助洗剂、多价螯合剂、螯合剂、防腐剂、pH调节剂、组合防腐剂/抗细菌剂、消毒剂、着色剂、流变改性剂、抗氧化剂、抗寄生生物剂、止痒剂、抗真菌剂、防腐活性物质、生物活性物质、收敛剂、角质层分离活性物质、局部麻醉剂、抗刺痛剂、抗红肿剂、皮肤抚慰剂、外用止痛剂、成膜剂、皮屑脱落剂、防晒剂、除臭剂、止汗剂、芳香剂,以及本领域技术人员已知的各种其他任选成分。
抗微生物剂
本公开的抗微生物组合物包含可以是羟基苯乙酮的抗微生物剂。如上所述,羟基苯乙酮因其抗微生物特性而为人所知。羟基苯乙酮是一种呈无色结晶固体形式的简单的芳香酮。羟基苯乙酮通常在成品中以0-1.0%(以重量计)的水平使用,在个人护理产品中提供多种益处,诸如除了其抗菌和防腐增强益处之外的抗氧化和抗刺激活性。由下面的结构表示,羟基苯乙酮是一种有效的广谱抗微生物剂,但是如上所述,其固有地具有有限的水溶性,这使得其难以共混到高度含水的制剂中,诸如许多个人护理产品中使用的那些制剂。
对羟基苯乙酮
在集中于呈浓缩物形式的抗微生物组合物的本公开中,羟基苯乙酮可以占组合物的至少10重量%。在一些实施方案中,按呈浓缩物形式的组合物的重量计,羟基苯乙酮可以占组合物的大于12重量%,大于15重量%,或者甚至大于20重量%。
在浓缩物被稀释后,在一些实施方案中,按组合物的重量计,羟基苯乙酮可以占组合物的小于约1.0重量%,或小于约0.5重量%,或小于约0.2重量%。
增溶剂
本公开的组合物还可以包含增溶剂。增溶剂可以帮助羟基苯乙酮溶解到液体浓缩物中。如将在下面进一步详细讨论,所研究的增溶剂包括甘油醚-7苯甲酸酯、己基甘油、甲基丙二醇、PPG-2苯基醚、苯氧基异丙醇、丙二醇、丁二醇、1,2-己二醇、异戊二烯二醇、戊二醇、丁基辛醇和辛酰二醇。
进行了最初的研究来解决羟基苯乙酮的问题,并且进行了实验来将羟基苯乙酮共混到液体浓缩物中,所述液体浓缩物包括高浓度的羟基苯乙酮和相对低数量和浓度的其他制剂成分,诸如增溶剂。优选尝试使用不超过两种或三种额外的成分,以使添加到制剂产品包装上的成分列表中的成分数量最少。
实验中使用的成分是化妆产品中常用的增溶剂。使用本文的测试方法部分中描述的方法进行稳定性测试。早期的稳定性测试集中于将各种增溶剂以2:1比率与羟基苯乙酮在50℃下混合,然后使样品在室温下放置数天,以确定是否会形成沉淀物。重点放在易于用水稀释的增溶剂上,以产生在延长的保质期内保持稳定的最终产品。
在检测的增溶剂中,只有两种在室温下储存4天后以2:1比率与羟基苯乙酮混合时没有出现沉淀物。这些增溶剂是丁二醇和异戊二烯二醇。其他增溶剂,甚至其他二醇增溶剂(诸如戊二醇、甲基丙二醇和1,2-己二醇)都不能在室温下保持羟基苯乙酮的稳定性。表1描述了许多被评估的组合。如果代码在25℃下4天的稳定性测试中产生沉淀物,则所述代码在5℃下1个月未进行测试,标记为“N/T”。
表1:与羟基苯乙酮和各种增溶剂的共混物
如表1中所示,大多数增溶剂不能与羟基苯乙酮混合,并且在25℃下保持稳定4天。代码G和J(分别包括增溶剂丁二醇和异戊二烯二醇)显示,在25℃下储存4天后,溶液中不具有沉淀物。然而,这些在室温下经过短期老化的共混物继续在室温下储存一个月,并且在5℃冰箱中放置一个月。此后,用羟基苯乙酮溶解的具有丁二醇的代码G和具有异戊二烯二醇的代码J都显示出沉淀物,因此没有通过稳定性测试。
由于有效的浓缩物共混物必须能够在广泛范围的温度内生存而不沉淀,所以人们进一步努力改善浓缩物共混物在低温下的稳定性。尽管增加增溶剂的浓度和降低浓缩物中羟基苯乙酮的浓度最终会得到稳定的共混物,但增加增溶剂的浓度会导致最终稀释溶液中所述物质的比例增加。这增加了最终溶液的成本,并且也增加了最终制剂中非水成分的浓度,这与许多消费者对具有最少添加剂的高水产品的期望相反。因此,不是简单地增加增溶剂的浓度,进行进一步的研究以向浓缩物中添加额外的成分,但是集中于可能在最终制剂中发现的成分。这样,可以提高浓缩物的稳定性,而不增加最终产品中非水成分的成本或浓度。
通过添加表面活性剂作为额外成分对制剂进行了进一步的实验,因为许多个人护理制剂利用表面活性剂来溶解油并提供去污力。最初选择非离子表面活性剂是因为它们通常用于溶解香料和植物油,通常不贵,并且在最终制剂中比阳离子或阴离子表面活性剂具有更小的相容性问题风险。
个人护理产品中常用的一种特殊的非离子表面活性剂是聚山梨醇酯-20(来自BASF的Eumulgin SML-20)。如表1中的代码K所示,聚山梨醇酯-20与羟基苯乙酮和丁二醇以10:20:9的重量比(丁二醇/聚山梨醇酯20/羟基苯乙酮)在非水共混物中混合。代码K成功通过了从5℃到55℃的各种温度下的稳定性测试,没有出现沉淀。测试了这三种成分的其他比率,并且也在5℃和25℃下保持稳定至少一个月,包括20:15:10、10:15:10和10:25:10的丁二醇/聚山梨醇酯-20/羟基苯乙酮比率。然而,20:5:10和20:15:20比率在这些条件下没有表现出稳定性,因为从浓缩物共混物中出现沉淀。
还用包含丁二醇和羟基苯乙酮的组合物测试了除聚山梨醇酯-20之外的其他非离子表面活性剂。如表2中所记录,用26%的羟基苯乙酮和51%的丁二醇对23%的各种非离子表面活性剂完成了1个月和3个月的稳定性测试。此稳定性测试是在5℃、25℃和40℃下完成的。
表2:用非离子表面活性剂进行稳定性测试
如表2中所示,各种不同的非离子表面活性剂通过了5℃至40℃下1个月和3个月的稳定性测试。阳离子和阴离子表面活性剂没有被研究,因为它们在最终制剂中可能有更大的相容性问题风险。
在一些实施方案中,本公开的浓缩组合物可以包含占组合物的至少25%(按重量计)的非离子表面活性剂。在一些实施方案中,非离子表面活性剂可以占组合物的大于30%、大于35%、大于40%、大于45%或甚至大于50%(按重量计)。
在一些实施方案中,非离子表面活性剂的量按最终稀释的抗微生物组合物的总重量计可以在0.01%至30%、或10%至30%、或0.05%至20%、或0.10%至15%的范围内。在一些实施方案中,非离子表面活性剂的量按最终稀释的抗微生物组合物的总重量计可以在0.01%至10.0%、或0.01%至5.0%或0.01%至1.0%的范围内。
还完成了额外的稳定性测试,以查看组合物中其他二醇(包括羟基苯乙酮)的稳定性。表3提供了20:10:9比率(51%:26%:23%)的二醇∶羟基苯乙酮∶聚山梨醇酯20的各种二醇增溶剂的稳定性测试结果。
表3:用各种二醇增溶剂进行稳定性测试
从表3中记录的结果可以看出,各种二醇可以提供足够的稳定性,而其他二醇则不能。例如,甘油、1,2-己二醇和辛酰二醇不能提供足够的稳定性。但是,丙二醇、丁二醇和甲基丙二醇都提供了足够的稳定性结果。从这些结果来看,似乎包含具有少于六个碳的碳链的二醇对于获得足够的稳定性是优选的。
此外,表3记录的稳定性测试结果还提供,如果从组合物中除去聚山梨醇酯-20的非离子表面活性剂,则不能获得适当的稳定性。因此,在二醇和羟基苯乙酮的一些组合物和用量中,似乎非离子表面活性剂可能有利于获得稳定的浓缩物组合物。
除了由羟基苯乙酮、丁二醇和表面活性剂组成的共混物之外,可以向浓缩物中添加第二种更大链长的二醇,以便促进第二种抗微生物成分的掺入。辛酰二醇(来自Inolex的Lexgard O或来自Symrise的Hydrolite CG)是一种具有已知抗微生物特性的1,2-二醇。它可以与羟基苯乙酮联合用作有效的共抗菌剂。辛酰二醇具有有限的水溶性,因此也难以以高浓度掺入水性制剂浓缩物中。然而,当在浓缩物中添加丁二醇、非离子表面活性剂和羟基苯乙酮时,可以产生在各种温度下长期稳定的浓缩物。例如,将30份辛酰二醇添加到20:9:10的丁二醇/聚山梨醇酯-20/羟基苯乙酮共混物中产生在5℃至40℃下稳定至少一个月的浓缩物。
事实上,即使在不存在非离子表面活性剂的情况下,或者当组合物基本上不含非离子表面活性剂时,掺入辛酰二醇和另一种短链二醇的共混物也可以保持稳定。为了本文的目的,当浓缩组合物包含少于1%的非离子表面活性剂时,其可以基本上不含非离子表面活性剂。表4总结了被评估的辛酰二醇、短链二醇和羟基苯乙酮的组合,以及它们相应的稳定性结果。
表4:使用两种二醇增溶剂进行稳定性测试
如表4中所记录,在不包括非离子表面活性剂的代码中,相对于羟基苯乙酮,辛酰二醇的显著浓度可能是实现稳定性所必需的。例如,30/20/10的辛酰二醇/丁二醇/羟基苯乙酮混合物在5℃和25℃下稳定至少一个月(代码R),30/20/10的辛酰二醇/甲基丙二醇/羟基苯乙酮混合物(代码Q)也是如此。这些结果是对仅利用辛酰二醇作为溶剂的浓缩物性能的改进,因为辛酰二醇在低温下易于固化。例如,3份辛酰二醇与1份羟基苯乙酮的共混物(代码T)在5℃下几天后完全固化,如果在制造环境中发生,这可能会导致处理上的挑战。
本公开的抗微生物浓缩组合物的一些实施方案可以合适地由至少一种二醇制成,所述至少一种二醇可以包含具有少于六个碳的碳链。在一些实施方案中,二醇可以占浓缩物组合物的大于20%(按重量计),或者在一些实施方案中,占组合物的大于25重量%、大于30重量%、大于35重量%或大于40重量%。
如上所述,在一些实施方案中,组合物中可以使用两种不同的二醇。在一些实施方案中,两种不同的二醇可以包含具有少于六个碳的碳链的第一种二醇和第二种二醇。在优选的实施方案中,第一种二醇可以包括丁二醇、甲基丙二醇及它们的组合中的至少一种。在一些实施方案中,第二种二醇可以是辛酰二醇。在一些实施方案中,总二醇重量百分比(例如,组合的第一种二醇重量百分比和第二种二醇重量百分比)可以是至少75%或至少80%。在一些实施方案中,总二醇重量百分比与羟基苯乙酮的量的比率可以大于4.0。在一些实施方案中,第二种二醇(诸如辛酰二醇)的重量百分比与羟基苯乙酮的重量百分比的比率可以大于2.5。
在最终的稀释形式中,在一些实施方案中,抗微生物组合物可以包含一种或多种二醇,其量为组合物的约0.01重量%至约1.0重量%或约0.1重量%至约0.5重量%。
载剂
本公开的抗微生物浓缩物组合物可以随后用一种或多种常规和相容的载剂材料稀释和配制。一旦稀释,所述抗微生物组合物可以采用多种形式,包括但不限于水性溶液、凝胶、香膏、洗剂、混悬剂、霜剂、乳、油膏、软膏剂、喷雾剂、乳剂、油、树脂、泡沫、固体棒状物、气溶胶剂等。适用的液体载剂材料包括熟知的在化妆品领域、药物领域和医学领域用作软膏剂、洗剂、霜剂、药膏剂、气雾剂、凝胶剂、混悬剂、喷雾剂、泡沫剂、洗涤剂等等的基料的那些,并且可以按照已建立的水平使用。在稀释后,载剂可以占约0.01%至约99.98%(按组合物的总重量计),这取决于所用的载剂。
优选的载剂材料包括极性溶剂材料,诸如水。其他潜在的载剂包括润肤剂、湿润剂、多元醇、表面活性剂、酯、全氟化碳、有机硅和其他药学上可接受的载剂材料。在一个实施方案中,载剂是挥发性的,从而允许抗微生物成分立即沉积到所需的表面,同时通过缩短干性时间来改善产品的总体使用体验。这些挥发性载剂的非限制性实例包括5厘沲聚二甲基硅氧烷、环状聚甲基硅氧烷(Cyclomethicone)、甲基全氟异丁基醚、甲基全氟丁基醚、乙基全氟异丁基醚和乙基全氟丁基醚。与常规的挥发性载剂(诸如乙醇或异丙醇)不同,这些载剂不具有抗微生物作用。
在一个实施方案中,所述抗微生物组合物可以任选地包含一种或多种润肤剂,所述润肤剂典型地起到软化、抚慰和以其他方式润滑和/或润湿皮肤的作用。可以掺入到所述组合物中的合适润肤剂包括油,诸如烷基聚二甲基硅氧烷、烷基聚甲基硅氧烷、烷基聚二甲基硅氧烷共聚醇、苯基有机硅、烷基三甲基硅烷、聚二甲基硅氧烷、聚二甲基硅氧烷交联聚合物、环状聚甲基硅氧烷、羊毛脂及其衍生物、脂肪酯、脂肪酸、甘油酯和衍生物、丙二醇酯和衍生物、烷氧基化羧酸、烷氧基化醇、脂肪醇,以及它们的组合。
所述抗微生物组合物的一些实施方案可以包含一种或多种润肤剂,其中润肤剂的量为约0.01%(按所述组合物的总重量计)至约20%(按所述组合物的总重量计)、或约0.05%(按所述组合物的总重量计)至约10%(按所述组合物的总重量计)、或约0.10%(按所述组合物的总重量计)至约5%(按所述组合物的总重量计)。
在一些实施方案中,抗微生物组合物包含一种或多种酯。这些酯可以选自棕榈酸鲸蜡酯、棕榈酸硬脂酯、硬脂酸鲸蜡酯、月桂酸异丙酯、肉豆蔻酸异丙酯、棕榈酸异丙酯,以及它们的组合。脂肪醇包括辛基十二烷醇、月桂醇、肉豆蔻醇、鲸蜡醇、硬脂醇、山嵛醇,以及它们的组合。脂肪酸可以包括但不限于癸酸、十一碳烯酸、月桂酸、肉豆蔻酸、棕榈酸、硬脂酸、油酸、亚油酸、花生酸和山嵛酸。醚诸如桉叶脑、鲸蜡硬脂基葡糖苷、二甲基异山梨聚甘油基-3鲸蜡基醚、聚甘油基-3癸基十四烷醇、丙二醇肉豆蔻基醚以及它们的组合也可以适合用作润肤剂。在抗微生物组合物或本公开中使用的其他合适的酯化合物列于以下文献中:International Cosmetic Ingredient Dictionary and Handbook,第11版,CTFA,(January,2006)ISBN-10:1882621360、ISBN-13:978-1882621361,以及2007 Cosmetic Bench Reference,Allured Pub.Corporation(2007年7月15日)ISBN-10:1932633278、ISBN-13:978-1932633276,这两份文献均以引用方式并入本文,达到与本文相符的程度。
适合作为本公开的抗微生物组合物中的载剂的湿润剂包括例如甘油、甘油衍生物、透明质酸、透明质酸衍生物、甜菜碱、甜菜碱衍生物、氨基酸、氨基酸衍生物、糖胺聚糖、二醇、多元醇、糖、糖醇、氢化淀粉水解物、羟基酸、羟基酸衍生物、PCA的盐等,以及它们的组合。合适的湿润剂的具体实例包括蜂蜜、山梨醇、透明质酸、透明质酸钠、甜菜碱、乳酸、柠檬酸、柠檬酸钠、乙醇酸、乙醇酸钠、乳酰钠、尿素、丙二醇、丁二醇、戊二醇、乙氧基二甘醇、甲基葡糖醇聚醚-10、甲基葡糖醇聚醚-20、聚乙二醇(如International Cosmetic Ingredient Dictionary and Handbook中所列出,诸如PEG-2至PEG 10)、丙二醇、木糖醇、麦芽糖醇或它们的组合。
本公开的抗微生物组合物可以包含一种或多种湿润剂,其中湿润剂的量为约0.01%(按所述组合物的总重量计)至约20%(按所述组合物的总重量计)、或约0.05%(按所述组合物的总重量计)至约10%(按所述组合物的总重量计)、或约0.1%(按所述组合物的总重量计)至约5.0%(按所述组合物的总重量计)。
如上所述,在本公开的优选实施方案中,浓缩的抗微生物组合物可以用载剂(诸如水)稀释。例如,在抗微生物组合物是润湿组合物的情况下,诸如下文描述的与湿擦拭物一起使用的润湿组合物,所述组合物通常包括水以稀释浓缩的抗微生物组合物。这些抗微生物组合物可以适当地包含水,其中水的量为约0.01%(按所述组合物的总重量计)至约99.98%(按所述组合物的总重量计)、或约1.00%(按所述组合物的总重量计)至约99.98%(按所述组合物的总重量计)、或约50.00%(按所述组合物的总重量计)至约99.98%(按所述组合物的总重量计)、或约75.00%(按所述组合物的总重量计)至约99.98%(按所述组合物的总重量计)。在一些实施方案中,水的量可以占约50.00%(按所述组合物的总重量计)至约70.00%(按所述组合物的总重量计)。在一些实施方案中,水的量所占的比例可以大于90.00%(按所述组合物的总重量计)。
在抗微生物组合物充当洗涤剂(例如香波;表面清洁剂;或手部、面部或身体洗涤剂)的一个实施方案中,所述抗微生物组合物将可能包含一种或多种表面活性剂。在抗微生物组合物被包含在擦拭物中的一个实施方案中,所述抗微生物组合物还可能包含一种或多种表面活性剂。这些表面活性剂可以选自阴离子表面活性剂、阳离子表面活性剂、非离子表面活性剂、两性离子表面活性剂和两性表面活性剂。表面活性剂的量按最终稀释的组合物的总重量计可以在0.01%至30%、或10%至30%、或0.05%至20%、或0.10%至15%的范围内。在一些实施方案中,诸如当润湿组合物与擦拭物一起使用时,表面活性剂按最终稀释的润湿组合物的总重量计可以占小于5%。
合适的阴离子表面活性剂包括但不限于C8至C22烷烃硫酸盐、醚硫酸盐和磺酸盐。合适的磺酸盐包括伯C8至C22烷烃磺酸盐、伯C8至C22烷烃二磺酸盐、C8至C22烯烃磺酸盐、C8至C22羟基烷烃磺酸盐或烷基甘油基醚磺酸盐。阴离子表面活性剂的具体实例包括月桂基硫酸铵、月桂醇聚醚硫酸铵、月桂基硫酸三乙胺、月桂醇聚醚硫酸三乙胺、月桂基硫酸三乙醇胺、月桂醇聚醚硫酸三乙醇胺、月桂基硫酸单乙醇胺、月桂醇聚醚硫酸单乙醇胺、月桂基硫酸二乙醇胺、月桂醇聚醚硫酸二乙醇胺、月桂酸甘油单酯硫酸钠、月桂基硫酸钠、月桂醇聚醚硫酸钠、月桂醇聚醚硫酸钾、月桂基肌氨酸钠、月桂酰肌氨酸钠、月桂基硫酸钾、十三烷醇聚醚硫酸钠、甲基月桂酰基牛磺酸钠、月桂酰基羟乙基磺酸钠、月桂醇聚醚磺基琥珀酸钠、月桂酰基磺基琥珀酸钠、十三烷基苯磺酸钠、十二烷基苯磺酸钠、月桂基两性醋酸钠,以及它们的混合物。其他阴离子表面活性剂包括C8至C22酰基甘氨酸盐。合适的甘氨酸盐包括椰油酰甘氨酸钠、椰油酰甘氨酸钾、月桂酰甘氨酸钠、月桂酰甘氨酸钾、肉豆蔻酰甘氨酸钠、肉豆蔻酰甘氨酸钾、棕榈酰甘氨酸钠、棕榈酰甘氨酸钾、硬脂酰甘氨酸钠、硬脂酰甘氨酸钾、椰油酰甘氨酸铵,以及它们的混合物。用于形成甘氨酸盐的阳离子抗衡离子可以选自钠、钾、铵、烷醇铵和这些阳离子的混合物。
合适的阳离子表面活性剂包括但不限于烷基二甲胺、烷基酰胺基丙胺、烷基咪唑啉衍生物、季铵化胺乙氧基化物和季铵化合物。
合适的非离子表面活性剂包括但不限于与环氧烷,特别是与单独的环氧乙烷或与环氧乙烷和环氧丙烷一起反应的醇、酸、酰胺或烷基酚。具体的非离子表面活性剂是C6至C22烷基酚-环氧乙烷缩合物、C8至C13脂族伯或仲直链或支链醇与环氧乙烷的缩合产物,以及通过将环氧乙烷与环氧丙烷和乙二胺的反应产物缩合而制成的产物。其他非离子表面活性剂包括长链叔胺氧化物、长链叔膦氧化物和二烷基亚砜、烷基多糖、氧化胺、嵌段共聚物、蓖麻油乙氧基化物、十六油基醇乙氧基化物、十六硬脂基醇乙氧基化物、癸醇乙氧基化物、二壬基苯酚乙氧基化物、十二烷基苯酚乙氧基化物、封端乙氧基化物、醚胺衍生物、乙氧基化烷醇酰胺、乙二醇酯、脂肪酸烷醇酰胺、脂肪醇烷氧基化物、月桂醇乙氧基化物、单支链醇乙氧基化物、天然醇乙氧基化物、壬基苯酚乙氧基化物、辛基苯酚乙氧基化物、油基胺乙氧基化物、无规共聚物烷氧基化物、脱水山梨糖醇酯乙氧基化物、硬脂酸乙氧基化物、硬脂胺乙氧基化物、合成醇乙氧基化物、妥尔油脂肪酸乙氧基化物、牛脂胺乙氧基化物和三(十三烷醇)乙氧基化物。
合适的两性离子表面活性剂包括例如烷基氧化胺、烷基羟基磺基甜菜碱、有机硅氧化胺,以及它们的组合。合适的两性离子表面活性剂的具体实例包括例如4-[N,N-二(2-羟乙基)-N-十八烷基铵]-丁烷-1-羧酸盐、S-[S-3-羟丙基-S-十六烷基锍]-3-羟基戊烷-1-硫酸盐、3-[P,P-二乙基-P-3,6,9-三氧杂十四烷基磷鎓]-2-羟基丙烷-1-磷酸盐、3-[N,N-二丙基-N-3-十二烷氧基-2-羟丙基铵]-丙烷-1-膦酸盐、3-(N,N-二甲基-N-十六烷基铵)丙烷-1-磺酸盐、3-(N,N-二甲基-N-十六烷基铵)-2-羟基丙烷-1-磺酸盐、4-[N,N-二(2-羟乙基)-N-(2-羟基十二烷基)铵]-丁烷-1-羧酸盐、3-[S-乙基-S-(3-十二烷氧基-2-羟丙基)锍]-丙烷-1-磷酸盐、3-[P,P-二甲基-P-十二烷基磷鎓]-丙烷-1-膦酸盐、5-[N,N-二(3-羟丙基)-N-十六烷基铵]-2-羟基-戊烷-1-硫酸盐、月桂基羟基磺基甜菜碱,以及它们的组合。
合适的两性表面活性剂包括但不限于脂族季铵化合物、鏻鎓化合物和锍化合物的衍生物,其中脂族基团可以是直链或支链,并且其中脂族取代基之一含有约8至约18个碳原子,并且一个取代基含有阴离子基团,例如,羧基、磺酸根、硫酸根、磷酸根或膦酸根。说明性的两性表面活性剂是椰油二甲基羧甲基甜菜碱、椰油酰胺丙基甜菜碱、椰油基甜菜碱、油基甜菜碱、鲸蜡基二甲基羧甲基甜菜碱、月桂基双-(2-羟乙基)羧甲基甜菜碱、硬脂酰双-(2-羟丙基)羧甲基甜菜碱、油基二甲基γ-羧基丙基甜菜碱、月桂基双-(2-羟丙基)α-羧乙基甜菜碱、椰油酰两性基乙酸盐,以及它们的组合。磺基甜菜碱可以包括硬脂酰二甲基磺基丙基甜菜碱、月桂基二甲基磺基乙基甜菜碱、月桂基双-(2-羟乙基)磺基丙基甜菜碱,以及它们的组合。
流变改性剂
任选地,可以向抗微生物组合物中添加一种或多种流变改性剂,诸如增稠剂。合适的流变改性剂与抗微生物剂相容。如本文所用,“相容”是指当与抗微生物剂混合时不会不利地影响其抗微生物特性的化合物。
在抗微生物组合物中使用增稠体系来调节组合物的粘性和稳定性。具体地,增稠体系防止组合物在分配和使用所述组合物期间从手或身体流走。当抗微生物组合物与擦拭物产品一起使用时,可以使用较稠的制剂来防止所述组合物从擦拭物基材迁移。
所述增稠体系应当与本公开中所使用的化合物相容;也就是说,所述增稠体系在与抗微生物化合物组合使用时,不应当沉淀出来、不应当形成凝聚层,也不应当阻止使用者感知即将从所述组合物获得的调理有益效果(或其他所需的有益效果)。所述增稠体系可以包含增稠剂,增稠剂既可以提供所述增稠体系所需的增稠效果,又可以提供对使用者皮肤的调理效果。
增稠剂可以包括纤维素、树胶、丙烯酸酯、淀粉和各种聚合物。合适的实例包括但不限于羟乙基纤维素、黄原胶、瓜尔胶、马铃薯淀粉和玉米淀粉。在一些实施方案中,PEG-150硬脂酸酯、PEG-150二硬脂酸酯、PEG-175二异硬脂酸酯、聚甘油基-10山嵛酸酯/二十烷二酸酯、二硬脂醇聚醚-100IPDI、聚丙烯酰胺基甲基丙烷磺酸、丁基化PVP以及它们的组合可能是合适的。
虽然组合物的粘度通常将取决于所使用的增稠剂和组合物的其他组分,但组合物的增稠剂适当地提供粘度在大于1cP至约30,000cP或更高范围内的组合物。在另一个实施方案中,增稠剂提供粘度为约100cP至约20,000cP的组合物。在又一个实施方案中,增稠剂提供粘度为约200cP至约15,000cP的组合物。在组合物被包含在擦拭物中的实施方案中,粘度可以在约1cP至约2000cP范围内。在一些实施方案中,优选使组合物的粘度小于500cP。
典型地,本公开的抗微生物组合物包含呈最终稀释形式的增稠体系,所述增稠体系的量不超过约20%(按所述组合物的总重量计),或为约0.01%(按所述组合物的总重量计)至约20%(按所述组合物的总重量计)。在另一方面,所述增稠体系以最终稀释形式以约0.10%(按所述组合物的总重量计)至约10%(按所述组合物的总重量计)、或约0.25%(按所述组合物的总重量计)至约5%(按所述组合物的总重量计)、或约0.5%(按所述组合物的总重量计)至约2%(按所述组合物的总重量计)的量存在于抗微生物组合物中。
乳化剂
在一个实施方案中,抗微生物组合物可以包含疏水成分和亲水成分,诸如洗剂或霜剂。通常,这些乳剂具有分散相和连续相,并且通常利用添加表面活性剂或具有不同亲水/亲油平衡值(HLB)的表面活性剂的组合来形成。合适的乳化剂包括HLB值为0至20、或2至18的表面活性剂。合适的非限制性实例包括鲸蜡硬脂基聚氧乙烯醚-20、鲸蜡硬脂基葡糖苷、十六烷基聚氧乙烯醚-10、十六烷基聚氧乙烯醚-2、十六烷基聚氧乙烯醚-20、椰油酰胺MEA、甘油月桂酸酯、甘油硬脂酸酯、PEG-100硬脂酸酯、甘油硬脂酸酯、甘油硬脂酸酯SE、乙二醇二硬脂酸酯、乙二醇硬脂酸酯、异硬脂醇聚醚-20、月桂基聚氧乙烯醚-23、月桂基聚氧乙烯醚-4、卵磷脂、甲基葡萄糖倍半硬脂酸酯、油基聚氧乙烯醚-10、油基聚氧乙烯醚-2、油基聚氧乙烯醚-20、PEG-100硬脂酸酯、PEG-20杏仁甘油酯、PEG-20甲基葡萄糖倍半硬脂酸酯、PEG-25氢化蓖麻油、PEG-30二多羟基硬脂酸酯、PEG-4二月桂酸酯、PEG-40脱水山梨糖醇全油酸酯、PEG-60杏仁甘油酯、PEG-7橄榄油酸酯、PEG-7甘油基椰油酸酯、PEG-8二油酸酯、PEG-8月桂酸酯、PEG-8油酸酯、PEG-80脱水山梨糖醇月桂酸酯、聚山梨醇酯20、聚山梨醇酯60、聚山梨醇酯80、聚山梨醇酯85、丙二醇异硬脂酸酯、脱水山梨糖醇异硬脂酸酯、脱水山梨糖醇月桂酸酯、脱水山梨糖醇单硬脂酸酯、脱水山梨糖醇油酸酯、脱水山梨糖醇倍半油酸酯、脱水山梨糖醇硬脂酸酯、脱水山梨糖醇三油酸酯、硬脂酰胺MEA、硬脂醇聚醚-100、硬脂醇聚醚-2、硬脂醇聚醚-20、硬脂醇聚醚-21。这些组合物还可以包含产生液晶网络或脂质体网络的表面活性剂或表面活性剂组合。合适的非限制性实例包括OLIVEM 1000(INCI:鲸蜡硬脂醇橄榄油酸酯(和)脱水山梨糖醇橄榄油酸酯(可从HallStar Company(Chicago,IL)获得);ARLACEL LC(INCI:脱水山梨糖醇硬脂酸酯(和)山梨醇月桂酸酯,可从Croda(Edison,NJ)商购获得);CRYSTALCAST MM(INCI:β谷甾醇(和)蔗糖硬脂酸酯(和)蔗糖二硬脂酸酯(和)鲸蜡醇(和)硬脂醇,可从MMP Inc.(South Plainfield,NJ)商购获得);UNIOX CRISTAL(INCI:鲸蜡硬脂醇(和)聚山梨醇酯60(和)鲸蜡硬脂基葡糖苷,可从Chemyunion(SàoPaulo,Brazil)商购获得)。其他合适的乳化剂包括卵磷脂、氢化卵磷脂、溶血卵磷脂、磷脂酰胆碱、磷脂,以及它们的组合。
助剂成分
本公开的抗微生物组合物可以附加包含以既定的方式并且以既定的水平常规地存在于化妆品、药物、医学、家庭、工业或个人护理组合物/产品中的助剂成分。这些成分通常以抗微生物组合物的最终稀释形式添加。例如,抗微生物组合物可以包含用于联合疗法的附加的相容药物活性材料和相容材料,诸如抗氧化剂、抗寄生生物剂、止痒剂、抗真菌剂、防腐活性物质、生物活性物质、收敛剂、角质层分离活性物质、局部麻醉剂、抗刺痛剂、抗红肿剂、皮肤抚慰剂、外用止痛剂、成膜剂、皮屑脱落剂、防晒剂,以及它们的组合。
可以包括在本公开的抗微生物组合物中的其他合适的添加剂包括相容的着色剂、除臭剂、乳化剂、消泡剂(当不需要泡沫时)、润滑剂、皮肤调理剂、皮肤保护剂和皮肤有益剂(例如,芦荟和生育酚乙酸酯)、溶剂(例如,水溶性乙二醇和乙二醇醚、甘油、水溶性聚乙二醇、水溶性聚乙二醇醚、水溶性聚丙二醇、水溶性聚丙二醇醚、二甲基异山梨醇)、增溶剂、悬浮剂、助洗剂(例如,碳酸盐、碳酸氢盐、磷酸盐、磷酸氢盐、磷酸二氢盐、硫酸氢盐的碱金属和碱土金属盐)、润湿剂、pH调节成分(组合物的合适pH范围可以为约3.5至约8)、螯合剂、推进剂、染料和/或颜料,以及它们的组合。
可以适合于添加到抗微生物组合物中的另一种组分是芳香剂。可以使用任何相容的芳香剂。典型地,芳香剂以组合物的最终稀释形式以约0%(按所述组合物的重量计)至约5%(按所述组合物的重量计),并且更典型地为约0.01%(按所述组合物的重量计)至约3%(按所述组合物的重量计)的量存在。在一个理想的实施方案中,芳香剂将具有干净、新鲜和/或中性的香味,从而产生对最终消费者有吸引力的递送媒介物。
可以存在于抗微生物组合物中的有机防晒剂包括甲氧基肉桂酸乙基己酯、阿伏苯宗、氰双苯丙烯酸辛酯、二苯甲酮-4、苯基苯并咪唑磺酸、胡莫柳酯、氧苯酮、二苯甲酮-3、水杨酸乙基己酯,以及它们的混合物。
除了本文所讨论的抗微生物剂之外,抗微生物组合物还可以包含各种组合抗微生物剂以延长货架期。可以在本公开中使用的一些合适的组合抗微生物剂包括传统抗微生物剂。如本文所用,“传统抗微生物剂”是指历史上已被监管机构认可为提供抗微生物效果的化合物,诸如在欧盟附录V化妆品准用防腐剂清单中列出的那些。传统抗微生物剂包括但不限于:丙酸及其盐;水杨酸及其盐;山梨酸及其盐;苯甲酸及其盐和酯;甲醛;多聚甲醛;邻苯基苯酚及其盐;吡啶硫酮锌;无机亚硫酸盐;亚硫酸氢盐;氯代丁醇;苯甲酸对羟基苯甲酸酯,诸如对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯、对羟基苯甲酸乙酯、对羟基苯甲酸异丙酯、对羟基苯甲酸异丁酯、对羟基苯甲酸苄酯、对羟基苯甲酸甲酯钠和对羟基苯甲酸丙酯钠;脱氢乙酸及其盐;甲酸及其盐;二溴己脒定羟乙基磺酸盐;硫柳汞;苯汞盐;十一碳烯酸及其盐;海克替啶;5-溴-5-硝基-1,3-二氧六环;2-溴-2-硝基丙烷-1,3-二醇;二氯苄醇;三氯卡班;对氯间甲酚;三氯生;氯二甲苯酚;咪唑烷基脲;聚氨丙基双胍;苯氧乙醇,乌洛托品;季铵盐-15;氯咪巴唑;DMDM乙内酰脲;苄醇;羟甲辛吡酮乙醇胺;溴氯芬;o-伞花烃-5-醇;甲基氯异噻唑啉酮;甲基异噻唑啉酮;苄氯酚;氯乙酰胺;洗必泰;氯己定二醋酸盐;氯己定二葡萄糖酸盐;氯己定二盐酸盐;苯氧异丙醇;烷基(C12-C22)三甲基溴化铵和氯化铵;二甲基噁唑烷;二偶氯烷基脲;己脒定;己脒定二羟乙基磺酸盐;戊二醛;7-乙基二环噁唑啉;氯苯甘醚;羟甲基甘氨酸钠;氯化银;苄索氯铵;苯扎氯铵;苯扎溴铵;甲醛苄醇半缩醛;碘代丙炔基丁基氨基甲酸酯;乙基月桂酰精氨酸盐酸盐;柠檬酸和柠檬酸银。
可以添加到本公开的抗微生物组合物中的其他组合抗微生物剂包括非传统抗微生物剂,这些非传统抗微生物剂已知除了其主要功能之外还表现出抗微生物作用,但在历史上尚未被监管机构(诸如在欧盟附录V清单上)认可为抗微生物剂。这些非传统抗微生物剂的实例包括但不限于辛甘醇、椰油脂基PG-二甲基氯化铵磷酸酯钠、苯丙醇、乳酸及其盐、辛酰羟肟酸、乙酰丙酸及其盐、月桂酰乳酰乳酰乳酸钠、苯乙醇、脱水山梨糖醇辛酸酯、甘油癸酸酯、甘油辛酸酯、乙基己基甘油、对茴香酸及其盐、葡糖酸内酯、癸二醇、1,2-己二醇、葡萄糖氧化酶和乳过氧化物酶、明串珠菌属(leuconostoc)/萝卜根发酵产物滤液和甘油月桂酸酯。
抗微生物组合物中的组合抗微生物剂的量取决于所述组合物内存在的其他组分的相对量。例如,在一些实施方案中,所述组合抗微生物剂可以抗微生物组合物的最终稀释形式以介于约0.001%至约5%之间(按所述组合物的总重量计),在一些实施方案中介于约0.01%与约3%之间(按所述组合物的总重量计),并且在一些实施方案中介于约0.05%与约1.0%之间(按所述组合物的总重量计)的量存在于组合物中。在一些实施方案中,组合抗微生物剂可以抗微生物组合物的最终稀释形式以小于0.2%(以组合物的总重量计)的量存在于组合物中。
然而,在一些实施方案中,所述抗微生物组合物基本上不含任何组合抗微生物剂,但仍通过包含羟基苯乙酮和二醇提供了足够的抗微生物生长的功效。因此,在一些实施方案中,抗微生物组合物不不含传统的抗微生物剂或除羟基苯乙酮和二醇(诸如辛酰二醇)之外的任何其他非传统抗微生物剂。这些实施方案可以提供更简单的制剂和改善的消费者吸引力的益处。
递送媒介物
本公开的抗微生物组合物可以与可以充当所述抗微生物组合物的递送媒介物的产品组合使用。例如,抗微生物组合物可以掺入到基材中或基材上,所述基材诸如擦拭物基材、吸收基材、织物或布基材、薄纸或纸巾基材等。在一个实施方案中,抗微生物组合物可以与擦拭物基材组合使用以形成湿擦拭物,或者可以是用于与可以具有分散性的擦拭物组合使用的润湿组合物。在其他实施方案中,抗微生物组合物可以掺入到擦拭物中,所述擦拭物诸如湿擦拭物、手部擦拭物、面部擦拭物、化妆品擦拭物、布等。在还有其他实施方案中,本文所述的抗微生物组合物可以与许多个人护理产品(诸如吸收制品)组合使用。感兴趣的吸收制品是尿布、训练裤、成人失禁产品、女性卫生产品等;卫生纸或面巾纸;以及纸巾。感兴趣的个人防护装备制品包括但不限于面罩、罩衣、手套、帽子等。
在一个实施方案中,湿擦拭物可以包含用称为“润湿组合物”的水性溶液润湿的非织造材料,所述水性溶液可以包含本文所公开的抗细菌组合物、或完全由本文所公开的抗微生物组合物组成。如本文所用,非织造材料包括纤维材料或基材,其中所述纤维材料或基材包括具有以垫状方式随机排列的一根根纤维或长丝的结构的片材。非织造材料可以由多种工艺制成,包括但不限于气流成网工艺、湿法成网工艺(诸如使用基于纤维素的薄纸或纸巾)、水力缠结工艺、短纤维梳理和粘结、熔喷,以及溶液纺丝。
形成所述纤维材料的纤维可以由多种材料制成,包括天然纤维、合成纤维以及它们的组合。对纤维的选择可以取决于例如最终基材的预期最终用途和纤维成本。例如,合适的纤维可以包括但不限于天然纤维,诸如棉、亚麻、黄麻、大麻、羊毛、木浆等。类似地,合适的纤维还可以包括:再生纤维素纤维,诸如粘胶人造丝和铜铵人造丝;改性纤维素纤维,诸如醋酸纤维素;或合成纤维,诸如衍生自聚丙烯、聚乙烯、聚烯烃、聚酯、聚酰胺、聚丙烯酸等的那些。如上文简要讨论的,再生纤维素纤维包括所有种类的人造丝,以及衍生自粘胶纤维或化学改性纤维素的其他纤维,包括再生纤维素和溶剂纺丝纤维素,诸如Lyocell。在木浆纤维中,可以使用任何已知的造纸纤维,包括软木纤维和硬木纤维。例如,纤维可以是化学制浆或机械制浆的、漂白或未漂白的、原浆或回收的、高收率或低收率的,等等。可以使用经化学处理的天然纤维素纤维,诸如丝光纸浆、化学硬化或交联的纤维,或者磺化纤维。
此外,可以使用由微生物产生的纤维素和其他纤维素衍生物。如本文所用,术语“纤维素”旨在包括具有纤维素作为主要成分,并且具体地,至少包含50重量%的纤维素或纤维素衍生物的任何材料。因此,所述术语包括棉、典型的木浆、非木质纤维素纤维、醋酸纤维素、三醋酸纤维素、人造丝、热机械木浆、化学木浆、脱粘化学木浆、马利筋属植物或细菌纤维素。如果需要,也可以使用任何前述纤维中的一种或多种的共混物。
所述纤维材料可以由单层或多层形成。在多层的情况下,这些层通常以并置或面对面的关系定位,并且这些层的全部或一部分可以与相邻层结合。所述纤维材料也可以由多种单独的纤维材料形成,其中这些单独的纤维材料中的每一种都可以由不同类型的纤维形成。
气流成网非织造织物特别适合于用作湿擦拭物。气流成网非织造织物的基重可以在约20至约200克/平方米(gsm)范围内,且短纤维的旦尼尔数为约0.5至约10、长度为约6至约15毫米。湿擦拭物通常可以具有约0.025g/cc至约0.2g/cc的纤维密度。湿擦拭物通常可以具有约20gsm至约150gsm的基重。更理想地,基重可以为约30gsm至约90gsm。甚至更理想地,基重可以为约50gsm至约75gsm。
用于生产气流成网非织造基片的方法在例如公布的美国专利申请号2006/0008621中有所描述,所述专利申请以引用方式并入本文,达到与本文相符的程度。
在一些实施方案中,当将抗微生物组合物用作与基材一起的润湿组合物时,可以以约30%至约500%、或约125%至约400%、或约150%至约350%的添加百分比将润湿组合物施加于基材。
测试方法
稳定性测试:
本文所述的浓缩物组合物在实验室中通过首先在容器中混合所有的二醇和表面活性剂并充分共混来分批。然后将所述混合物加热至50℃并在混合下缓慢添加羟基苯乙酮。一旦所有羟基苯乙酮溶解,然后将混合物冷却至室温。
然后将每批样品放入2盎司的玻璃罐中并在选定的温度条件下(例如,5℃、25℃、40℃或此处注明的其他条件)放置老化。将在高于25℃的温度下老化的样品放入温控烘箱中,同时将在低于25℃的温度下储存的样品储存在温控冰箱或冰柜中。25℃的样品在受控的实验室环境中储存在室温下。
然后以本文所述的预定时间间隔(例如1个月)从老化室中取出样品,检查制剂的可见物理不稳定性迹象,包括沉淀、分离和浊度变化。任何可见的沉淀或分离迹象都被认为是所述稳定性试验的失败。然后将样品放回到老化室中,直到下一次评估。
实施方案
实施方案1:一种组合物,其包含:至少一种二醇,其中所述至少一种二醇包括包含具有少于六个碳的碳链的第一种二醇;非离子表面活性剂;羟基苯乙酮,其中所述羟基苯乙酮占所述组合物的至少10重量%。
实施方案2:如实施方案1所述的组合物,其中根据本文所述的稳定性试验,所述组合物在5℃下稳定至少1个月。
实施方案3:如实施方案1或2中任一项所述的组合物,其中所述第一种二醇选自由丁二醇、丙二醇和甲基丙二醇组成的组。
实施方案4:如前述实施方案中任一项所述的组合物,其中所述至少一种二醇包括第二种二醇。
实施方案5:如实施方案4所述的组合物,其中所述第二种二醇是辛酰二醇。
实施方案6:如前述实施方案中任一项所述的组合物,其中所述非离子表面活性剂包含聚山梨醇酯-20、聚山梨醇酯-80、PEG-40氢化蓖麻油、聚甘油-3癸酸酯、十三烷醇聚醚-6和十三烷醇聚醚-18中的至少一种。
实施方案7:如实施方案6所述的组合物,其中所述非离子表面活性剂包括聚山梨醇酯-20。
实施方案8:如前述实施方案中任一项所述的组合物,其中所述非离子表面活性剂与所述羟基苯乙酮的比率为至少1.0。
实施方案9:一种组合物,其包含:第一种二醇,所述第一种二醇包含具有少于六个碳的碳链;第二种二醇;非离子表面活性剂;和羟基苯乙酮。
实施方案10:如实施方案9所述的组合物,其中所述羟基苯乙酮占所述组合物的至少10重量%。
实施方案11:如实施方案9或10所述的组合物,其中所述第一种二醇选自由丁二醇、丙二醇和甲基丙二醇组成的组。
实施方案12:如实施方案9至11中任一项所述的组合物,其中所述第二种二醇是辛酰二醇。
实施方案13:如实施方案9至12中任一项所述的组合物,其中所述非离子表面活性剂包含聚山梨醇酯-20、聚山梨醇酯-80、PEG-40氢化蓖麻油、聚甘油-3癸酸酯、十三烷醇聚醚-6和十三烷醇聚醚-18中的至少一种。
实施方案14:如实施方案13所述的组合物,其中所述非离子表面活性剂包括聚山梨醇酯-20。
实施方案15:如实施方案9至14中任一项所述的组合物,其中根据本文所述的稳定性试验,所述组合物在5℃下稳定至少1个月。
实施方案16:一种组合物,其包含:呈所述组合物的第一重量百分比的第一种二醇;呈所述组合物的第二重量百分比的辛酰二醇,其中所述第一重量百分比和所述第二重量百分比构成所述组合物的总二醇重量百分比;和呈所述组合物的至少10重量%的量的羟基苯乙酮;其中所述总二醇重量百分比与所述羟基苯乙酮的所述量的比率大于4.0。
实施方案17如实施方案16所述的组合物,其中所述组合物基本上不含表面活性剂。
实施方案18:如实施方案16或17所述的组合物,根据本文所述的稳定性试验,所述组合物在5℃下稳定至少1个月。
实施方案19:如实施方案16至18中任一项所述的组合物,其中所述第一种二醇包括丁二醇、甲基丙二醇和它们的组合中的至少一种。
实施方案20:如实施方案16至19中任一项所述的组合物,其中所述组合物的所述第二重量百分比与所述羟基苯乙酮的所述量的比率大于2.5。
在介绍本公开的元素时,冠词“一个/种(a/an)”、“所述(the)”和“所述(said)”旨在表示存在一个或多个这些元素。词语“包含(comprising)”、“包括(including)”和“具有(having)”旨在为包含性的,意指可能存在所列元件之外的额外元件。在不脱离本公开的精神和范围的情况下,可对本公开进行许多修改和变化。因此,上述示例性实施方案不应当用来限制本公开的范围。
Claims (20)
1.一种组合物,其包含:
至少一种二醇,其中所述至少一种二醇包括包含具有少于六个碳的碳链的第一种二醇;
非离子表面活性剂;
羟基苯乙酮,其中所述羟基苯乙酮占所述组合物的至少10重量%。
2.如权利要求1所述的组合物,其中根据本文所述的稳定性测试,所述组合物在5℃下稳定至少1个月。
3.如权利要求1所述的组合物,其中所述第一种二醇选自由丁二醇、丙二醇和甲基丙二醇组成的组。
4.如权利要求1所述的组合物,其中所述至少一种二醇包括第二种二醇。
5.如权利要求4所述的组合物,其中所述第二种二醇是辛酰二醇。
6.如权利要求1所述的组合物,其中所述非离子表面活性剂包含聚山梨醇酯-20、聚山梨醇酯-80、PEG-40氢化蓖麻油、聚甘油-3癸酸酯、十三烷醇聚醚-6和十三烷醇聚醚-18中的至少一种。
7.如权利要求6所述的组合物,其中所述非离子表面活性剂包括聚山梨醇酯-20。
8.如权利要求1所述的组合物,其中所述非离子表面活性剂与所述羟基苯乙酮的比率为至少1.0。
9.一种组合物,其包含:
第一种二醇,所述第一种二醇包含具有少于六个碳的碳链;
第二种二醇;
非离子表面活性剂;和
羟基苯乙酮。
10.如权利要求9所述的组合物,其中所述羟基苯乙酮占所述组合物的至少10重量%。
11.如权利要求9所述的组合物,其中所述第一种二醇选自由丁二醇、丙二醇和甲基丙二醇组成的组。
12.如权利要求9所述的组合物,其中所述第二种二醇是辛酰二醇。
13.如权利要求9所述的组合物,其中所述非离子表面活性剂包含聚山梨醇酯-20、聚山梨醇酯-80、PEG-40氢化蓖麻油、聚甘油-3癸酸酯、十三烷醇聚醚-6和十三烷醇聚醚-18中的至少一种。
14.如权利要求13所述的组合物,其中所述非离子表面活性剂包括聚山梨醇酯-20。
15.如权利要求9所述的组合物,其中根据本文所述的稳定性测试,所述组合物在5℃下稳定至少1个月。
16.一种组合物,其包含:
呈所述组合物第一重量百分比的第一种二醇;
呈所述组合物的第二重量百分比的辛酰二醇,其中所述第一重量百分比和所述第二重量百分比构成所述组合物的总二醇重量百分比;和
呈所述组合物的至少10重量%的量的羟基苯乙酮;
其中所述总二醇重量百分比与所述羟基苯乙酮的所述量的比率大于4.0。
17.如权利要求16所述的组合物,其中所述组合物基本上不含表面活性剂。
18.如权利要求16所述的组合物,根据本文所述的稳定性测试,所述组合物在5℃下稳定至少1个月。
19.如权利要求16所述的组合物,其中所述第一种二醇包括丁二醇、甲基丙二醇和它们的组合中的至少一种。
20.如权利要求16所述的组合物,其中所述组合物的所述第二重量百分比与所述羟基苯乙酮的所述量的比率大于2.5。
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