CN106070214A - 液体抗菌组合物以及生产该组合物的方法 - Google Patents
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Abstract
本发明公开了液体抗菌组合物以及生产该组合物的方法。本发明提供一种液体抗菌组合物,其包含(A)对羟基苯甲酸酯和(B)水可混溶有机溶剂,其中(A)对羟基苯甲酸酯为两种或更多种选自以下的酯:对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸异丙酯、对羟基苯甲酸丁酯、对羟基苯甲酸异丁酯和对羟基苯甲酸苄酯;(B)水可混溶有机溶剂包含(B‑1)至少一种选自丙二醇、丁二醇、乙醇和聚乙二醇的有机溶剂,和(B‑2)2‑苯氧基乙醇;并且(A)与(B)的重量比为1∶1至1∶3,并且(B‑1)与(B‑2)的重量比为1∶1至1∶3。
Description
发明背景
发明领域
本发明要求根据巴黎公约的基于日本专利申请号2015-093006(申请日:2015年4月30日)的优先权,其全部内容在此通过引入并入本文。
本发明涉及包含对羟基苯甲酸酯的液体抗菌组合物。
相关技术描述
对羟基苯甲酸酯具有优异的抗菌活性、低毒性和低刺激性,因此各种酯作为抗菌剂用于化妆品等中。然而,对羟基苯甲酸酯在水中具有极其低的溶解度,并且因此根据其添加量可能以晶体形式沉淀。因此,当将对羟基苯甲酸酯添加到待抗菌的产品中时,已经通常使用包含醇,例如乙醇作为增溶剂的抗菌组合物。
然而,包含增溶剂的抗菌组合物在低温下储存期间甚至也可能以晶体形式沉淀,并且不能以高浓度包含对羟基苯甲酸酯。单一的对羟基苯甲酸酯不能提供足够的抗菌效果,并且经常同时使用多种对羟基苯甲酸酯以弥补抗菌效果。然而,在这种抗菌组合物中,在低温下在储存期间的晶体沉淀是明显的,而且得到的配制品很难处理。
为了改进如上所述对羟基苯甲酸酯的溶解度,迄今为止已经进行了各种研究。
JP-B-S37-17994描述了抗霉剂,其包含两种或更多种对羟基苯甲酸酯的低共熔混合物或低共熔物作为主要组分。在该抗霉剂中,多种对羟基苯甲酸酯形成低共熔混合物或低共熔物,以显著改进其在水中的溶解度;然而,该低共熔混合物或低共熔物容易再结晶,并且必须添加乳化剂等以稳定地供应配制品。
JP-A-H09-124414描述了协同抗微生物剂,其包含1,2-二溴-2,4-二氰基丁烷和至少一种对羟基苯甲酸酯。然而,这种抗微生物剂价格高,并且在毒性和安全性数据方面并不充分。
JP-A-2003-252799描述了对羟基苯甲酸的增溶助剂,其包含含有2-甲基丙烯酰氧基乙基磷酰基胆碱/甲基丙烯酸丁酯共聚物的水性溶液。然而,2-甲基丙烯酰氧基乙基磷酰基胆碱和甲基丙烯酸丁酯必须在惰性气体气氛下经历自由基聚合以获得共聚物,并且因此这种增溶助剂在其生产中非常麻烦,并且价格高。
因此,期望便宜、安全和抗菌效果优异,并且在低温下储存期间抑制对羟基苯甲酸酯的再结晶的抗菌组合物。
发明概述
本发明的目的为提供在低温下储存期间具有改进的稳定性并且在抗菌性能方面优异的液体抗菌组合物。
本发明人已经仔细地进行了研究。结果,本发明人发现通过以特定的比率混合特定的对羟基苯甲酸酯和特定的有机溶剂,防止了在低温下储存期间对羟基苯甲酸酯的沉淀,并且同时获得含有高浓度的对羟基苯甲酸酯的水性溶液。这些发现使得本发明得以完成。
即,本发明提供一种液体抗菌组合物,其包含
(A)对羟基苯甲酸酯,和
(B)水可混溶有机溶剂,
其中(A)对羟基苯甲酸酯为两种或更多种选自以下的酯:对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸异丙酯、对羟基苯甲酸丁酯、对羟基苯甲酸异丁酯和对羟基苯甲酸苄酯;
(B)水可混溶有机溶剂包含(B-1)至少一种选自丙二醇、丁二醇、乙醇和聚乙二醇的有机溶剂,和(B-2)2-苯氧基乙醇;并且
(A)与(B)的重量比为1∶1至1∶3,并且(B-1)与(B-2)的重量比为1∶1至1∶3。
本发明还提供一种液体抗菌组合物的生产方法,其包括如下步骤:在40-80℃的温度下将(A)对羟基苯甲酸酯溶解在(B)水可混溶有机溶剂中,
其中(A)对羟基苯甲酸酯为两种或更多种选自以下的酯:对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸异丙酯、对羟基苯甲酸丁酯、对羟基苯甲酸异丁酯和对羟基苯甲酸苄酯;
(B)水可混溶有机溶剂包含(B-1)至少一种选自丙二醇、丁二醇、乙醇和聚乙二醇的有机溶剂,和(B-2)2-苯氧基乙醇;并且
(A)与(B)的重量比为1∶1至1∶3,并且(B-1)与(B-2)的重量比为1∶1至1∶3。
发明详述
本发明的液体抗菌组合物中使用的对羟基苯甲酸酯可以为任何组合,只要该组合包含两种或更多种选自以下的酯:对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸异丙酯、对羟基苯甲酸丁酯、对羟基苯甲酸异丁酯和对羟基苯甲酸苄酯。一方面,对羟基苯甲酸酯为两种或更多种酯,优选选自以下的两种:对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯和对羟基苯甲酸丁酯。考虑到在水中的溶解度和抗菌效果,优选对羟基苯甲酸甲酯和对羟基苯甲酸乙酯的组合、对羟基苯甲酸丙酯和对羟基苯甲酸丁酯的组合以及对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的组合。
对羟基苯甲酸酯的共混比率可以根据所选的酯的种类和数目而不同。例如,当选择对羟基苯甲酸甲酯和对羟基苯甲酸乙酯时,对羟基苯甲酸甲酯和对羟基苯甲酸乙酯的共混比率优选3∶1至1∶3,更优选2∶1至1∶2,和进一步优选1∶0.7至1∶1.5。
当选择对羟基苯甲酸丙酯和对羟基苯甲酸丁酯时,对羟基苯甲酸丙酯和对羟基苯甲酸丁酯的重量比优选3∶1至1∶3,更优选2∶1至1∶2,和进一步优选1∶0.7至1∶1.5。
当选择对羟基苯甲酸甲酯和对羟基苯甲酸丙酯时,对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的重量比优选3∶1至1∶3,更优选2∶1至1∶2,和进一步优选1∶0.7至1∶1.5。
本发明的液体抗菌组合物中的对羟基苯甲酸酯的百分比没有特别限制,只要酯的量在低温下储存期间不引起沉淀,但是对羟基苯甲酸酯的总量优选25-50wt%,更优选30-45wt%,并且进一步优选33-42wt%,基于该液体抗菌组合物的总量。当基于液体抗菌组合物的总量的对羟基苯甲酸酯的总量小于25wt%时,抗菌效果倾向于不足,并且当基于液体抗菌组合物的总量的对羟基苯甲酸酯的总量大于50wt%时,在低温下储存期间倾向于容易导致沉淀。
本发明使用的水可混溶有机溶剂为包含第一和第二有机溶剂的混合溶剂。该第一有机溶剂(B-1)为至少一种选自丙二醇、丁二醇、乙醇和聚乙二醇的有机溶剂,并且考虑到对羟基苯甲酸酯的溶解度,优选丙二醇(例如,1,2-丙二醇或1,3-丙二醇)或丁二醇(例如,1,3-丁二醇或1,4-丁二醇)。第二有机溶剂(B-2)为2-苯氧基乙醇。
在该水可混溶有机溶剂中的有机溶剂(B-1)与有机溶剂(B-2)的重量比应该为1∶1至1∶3。有机溶剂(B-1)与有机溶剂(B-2)的重量比优选为1∶1.5至1∶2.5,并且更优选1∶1.8至1∶2.2。当有机溶剂(B-2)的重量相对于有机溶剂(B-1)的重量小于相等的量时,对羟基苯甲酸酯倾向于在低温下沉淀,并且当该有机溶剂(B-2)的重量大于有机溶剂(B-1)重量的3倍量时,对羟基苯甲酸酯在水中的溶解度倾向于降低。
本发明的液体抗菌组合物中该水可混溶有机溶剂的百分比没有特别限制,只要该有机溶剂的量是在该量下对羟基苯甲酸酯是可溶的量,但是基于该液体抗菌组合物的总量的该水可混溶有机溶剂的总量优选50-75wt%,更优选55-70wt%,并且进一步优选58-67wt%。当基于该液体抗菌组合物的总量的该水可混溶有机溶剂的总量小于50wt%时,在低温下储存期间倾向于容易发生对羟基苯甲酸酯的沉淀。当基于该液体抗菌组合物的总量的该水可混溶有机溶剂的总量大于75wt%时,抗菌效果倾向于不足。
在本发明的液体抗菌组合物中该对羟基苯甲酸酯和该水可混溶有机溶剂的重量比应为1∶1至1∶3,并且优选1∶1.2至1∶2,并且更优选1∶1.4至1∶1.8。当该水可混溶有机溶剂的重量相对于该对羟基苯甲酸酯的重量小于相等的量时,在低温下储存期间倾向于容易发生对羟基苯甲酸酯的沉淀。当该水可混溶有机溶剂的重量大于该对羟基苯甲酸酯的重量的3倍量时,抗菌效果倾向于不足。
本发明的液体抗菌组合物可以通过以下步骤生产:以1∶1至1∶3的重量比混合对羟基苯甲酸酯和水可混溶有机溶剂,并且在40-80℃的温度下使对羟基苯甲酸酯溶解。对羟基苯甲酸酯溶解的温度优选为45-75℃,并且更优选50-70℃。
因此得到的液体抗菌组合物在冷却到室温之后可以用于各种需要抗菌处理的对象。作为将该液体抗菌组合物施用至待抗菌的对象上的方法,可以将所得的液体抗菌组合物直接施用至该对象,或者如果需要,在该液体抗菌组合物形成水性溶液之后,可以随后将该溶液施用至对象。用于将该液体抗菌组合物施用至对象的方法的实例包括但不限于,添加、混合、涂覆、浸渍等。
待抗菌的特定对象的实例包括化妆品、药物、食物、墨水、金属加工油、粘合剂、水、涂料、制冷剂、驱虫剂、芳香剂、除臭剂、无纺织物等。
将该液体抗菌组合物施用至待抗菌的对象,使得基于该对象的总重量的对羟基苯甲酸酯的百分比优选为0.01-5wt%,更优选0.02-1wt%,并且进一步优选0.05-0.5wt%。
本发明的液体抗菌组合物可以以使得在低温下储存期间的稳定性和抗菌性能不受影响的范围包含助剂。该助剂的实例包括pH调节剂、表面活性剂、稳定剂、粘度调节剂、着色剂、香料等。该助剂的百分比优选为0.01-1wt%,基于该液体抗菌组合物的总量。
本发明将通过下述实施例进一步举例说明。
实施例
实施例1-7和比较例1-20
液体抗菌组合物的生产
将显示在表1中的对羟基苯甲酸酯(A)添加至显示在相同表中的水可混溶有机溶剂(B)中,该水可混溶有机溶剂(B)已经通过提前混合溶剂获得,并且当加热至约60℃时,材料溶解,以产生液体抗菌组合物。
表1
续表1
续表1
稳定性测试
将5毫升如上所述生产的每种液体抗菌组合物放置于具有50mL容积的小瓶中,该瓶紧紧地加盖并储存在4℃下的冷冻机中,然后7天后观察外观。
本发明的液体抗菌组合物(实施例1-7)没有显示出沉淀等,并且是稳定的。结果显示在表2中。
表2
抗菌活性测试1
关于实施例1、3和4以及比较例3、6和17各自的组合物,其包含对羟基苯甲酸甲酯并且在稳定性测试中是稳定的且没有沉淀,根据日本化学疗法学会的标准方法(StandardMethod of Japanese Society of Chemotherapy)(肉汤微稀释法)测量最小抑菌浓度(MIC)。
将每种组合物用无菌水稀释以制备具有0.003-0.4wt%组合物浓度的药物溶液,将已经调节其浓度至指定浓度的两倍浓度的SCD肉汤培养基(由Nihon PharmaceuticalCo.,Ltd.生产)以与药物溶液相同的量添加,并且在搅拌之后,将各170μL/孔分配至微量滴定板(96-孔)。然后将细菌液体用生理盐水稀释以具有104cfu/ml的浓度,该细菌液体通过在30℃下在SCD培养基中培养每种下述测试细菌20小时而得到,并且将各10μL/孔接种至如上所述产生的微量滴定板上并且对其已经分配了培养基。将其在培养箱中在30℃下培养48小时,通过视觉确认存在或不存在细菌生长,并且测量MIC。结果显示在表3中。
测试细菌1:大肠杆菌NIHJ-JC2
测试细菌2:金黄色葡萄球菌1F013276
测试细菌3:绿脓杆菌ATCC13736
测试细菌4:白色念珠菌FDA2 138
测试细菌5:黑曲霉ATCC 16404
表3
抗菌活性测试2
关于实施例2和5-7以及比较例8、10和19各自的组合物,其包含对羟基苯甲酸丁酯并且在稳定性测试中是稳定的且没有沉淀,使用与抗菌活性测试1相同的方法和相同的测试细菌测量MIC。结果显示在表4中。
表4
水中溶解度的测试
关于实施例1、3和4以及比较例3、6和17各自的组合物,其包含对羟基苯甲酸甲酯并且在稳定性测试中是稳定的且没有沉淀,将100mL的水性饱和溶液(在对羟基苯甲酸酯沉淀的时间点确定其达到饱和),和在水性溶液中的对羟基苯甲酸酯的总量相互之间进行比较。分别地,关于实施例2和5-7以及比较例8、10和19各自的组合物,其包含对羟基苯甲酸丁酯并且是稳定的且没有沉淀,也以如上所述相同的方式进行比较。
包含本发明的液体抗菌组合物的水性溶液与比较例的水性溶液相比以更高浓度包含对羟基苯甲酸酯。结果显示在表5和6中。
表5
表6
Claims (9)
1.一种液体抗菌组合物,其包含
(A)对羟基苯甲酸酯,和
(B)水可混溶有机溶剂,
其中(A)对羟基苯甲酸酯为两种或更多种选自以下的酯:对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸异丙酯、对羟基苯甲酸丁酯、对羟基苯甲酸异丁酯和对羟基苯甲酸苄酯;
(B)水可混溶有机溶剂包含(B-1)至少一种选自丙二醇、丁二醇、乙醇和聚乙二醇的有机溶剂,和(B-2)2-苯氧基乙醇;并且
(A)与(B)的重量比为1∶1至1∶3,并且(B-1)与(B-2)的重量比为1∶1至1∶3。
2.根据权利要求1的液体抗菌组合物,其中基于该液体抗菌组合物的总量的(A)对羟基苯甲酸酯的总量为25-50wt%,并且基于该液体抗菌组合物的总量的(B)水可混溶有机溶剂的总量为50-75wt%。
3.根据权利要求1的液体抗菌组合物,其中(A)对羟基苯甲酸酯为对羟基苯甲酸甲酯和对羟基苯甲酸乙酯。
4.根据权利要求3的液体抗菌组合物,其中对羟基苯甲酸甲酯和对羟基苯甲酸乙酯的重量比为3∶1至1∶3。
5.根据权利要求1的液体抗菌组合物,其中(A)对羟基苯甲酸酯为对羟基苯甲酸丙酯和对羟基苯甲酸丁酯。
6.根据权利要求5的液体抗菌组合物,其中对羟基苯甲酸丙酯和对羟基苯甲酸丁酯的重量比为3∶1至1∶3。
7.根据权利要求1的液体抗菌组合物,其中(B-1)有机溶剂为丙二醇或丁二醇。
8.根据权利要求1的液体抗菌组合物,其中待抗菌的对象是选自以下的任一种:化妆品、药物、食物、墨水、金属加工油、粘合剂、工业用水、涂料、制冷剂、驱虫剂、芳香剂、除臭剂和无纺织物。
9.一种液体抗菌组合物的生产方法,包括如下步骤:在40-80℃的温度下将(A)对羟基苯甲酸酯溶解在(B)水可混溶有机溶剂中,
其中(A)对羟基苯甲酸酯为两种或更多种选自以下的酯:对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸异丙酯、对羟基苯甲酸丁酯、对羟基苯甲酸异丁酯和对羟基苯甲酸苄酯;
(B)水可混溶有机溶剂包含(B-1)至少一种选自丙二醇、丁二醇、乙醇和聚乙二醇的有机溶剂,和(B-2)2-苯氧基乙醇;并且
(A)与(B)的重量比为1∶1至1∶3,并且(B-1)与(B-2)的重量比为1∶1至1∶3。
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CN114028329A (zh) * | 2021-12-24 | 2022-02-11 | 沈阳兴齐眼药股份有限公司 | 含有联合抑菌剂的滴眼液制剂和包含其的产品 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0194466A2 (de) * | 1985-03-13 | 1986-09-17 | Giulini Chemie GmbH | Kombination zur antimikrobiellen und antioxidativen Stabilisierung von Externa und Körperpflegemitteln |
CN104222080A (zh) * | 2014-06-27 | 2014-12-24 | 中国人民解放军第三军医大学第一附属医院 | 对羟基安息香酸丙酯的羟丙基-β-环糊精超分子包合物、制备方法及使用方法 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3451122B2 (ja) * | 1994-02-02 | 2003-09-29 | 三菱鉛筆株式会社 | 水性インキ組成物 |
US5641808A (en) | 1995-09-01 | 1997-06-24 | Calgon Corporation | Synergistic antimicrobial composition of 1,2-dibromo-2,4-dicyanobutane and esters of parahydroxybenzoic acid |
JP2003252799A (ja) | 2002-03-04 | 2003-09-10 | Nof Corp | 脂溶性パラオキシ安息香酸類の溶解補助剤、溶液および用途 |
JP2005015401A (ja) * | 2003-06-26 | 2005-01-20 | Kao Corp | 防腐剤組成物、外用組成物及び防腐方法 |
US9445975B2 (en) * | 2008-10-03 | 2016-09-20 | Access Business Group International, Llc | Composition and method for preparing stable unilamellar liposomal suspension |
JP6430109B2 (ja) * | 2012-11-02 | 2018-11-28 | ロート製薬株式会社 | 外用組成物 |
CN103385241A (zh) * | 2013-08-19 | 2013-11-13 | 广州博嘉生物科技有限公司 | 一种复合防腐剂及其用途 |
-
2015
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-
2016
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0194466A2 (de) * | 1985-03-13 | 1986-09-17 | Giulini Chemie GmbH | Kombination zur antimikrobiellen und antioxidativen Stabilisierung von Externa und Körperpflegemitteln |
CN104222080A (zh) * | 2014-06-27 | 2014-12-24 | 中国人民解放军第三军医大学第一附属医院 | 对羟基安息香酸丙酯的羟丙基-β-环糊精超分子包合物、制备方法及使用方法 |
Non-Patent Citations (1)
Title |
---|
FERDINANDO GIORDANO 等: "Physical Properties of Parabens and Their Mixtures: Solubility inWater, Thermal Behavior", 《JOURNAL OF PHARMACEUTICAL SCIENCES》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108743575A (zh) * | 2018-06-21 | 2018-11-06 | 华南农业大学 | 对羟基苯甲酸丁酯在制备抗白色念珠菌药物中的应用 |
CN114028329A (zh) * | 2021-12-24 | 2022-02-11 | 沈阳兴齐眼药股份有限公司 | 含有联合抑菌剂的滴眼液制剂和包含其的产品 |
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