CN111465384B9 - 氯己定-环己基氨基磺酸盐络合物和包含其的口腔护理组合物 - Google Patents

氯己定-环己基氨基磺酸盐络合物和包含其的口腔护理组合物 Download PDF

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CN111465384B9
CN111465384B9 CN201780097593.XA CN201780097593A CN111465384B9 CN 111465384 B9 CN111465384 B9 CN 111465384B9 CN 201780097593 A CN201780097593 A CN 201780097593A CN 111465384 B9 CN111465384 B9 CN 111465384B9
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chlorhexidine
cyclohexylsulfamate
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郝志刚
程池原
潘龙
R.苏布拉曼亚姆
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Abstract

本公开提供一种氯己定-环己基氨基磺酸盐络合物，其具有式[C22H32Cl2N10][C6H12NO3S]2，所述络合物具有抗细菌和抗牙菌斑特性；以及包含所述络合物的口腔护理组合物，和制造和使用这些络合物和组合物的方法。

Description

氯己定-环己基氨基磺酸盐络合物和包含其的口腔护理组合物
背景技术
牙菌斑为形成于牙齿上的软沉积物并且由细菌和细菌副产物的积聚物
所属领域中已经建议多种抗细菌剂以延缓牙菌斑形成和与牙菌斑形成
为了将抗牙菌斑活性赋予到牙齿表面，必须使二双胍沉积在牙齿表面
因此，需要在牙齿表面处沉积二双胍，即氯己定，持续延长的时间段。
发明内容
氯己定被认为是常用于口腔护理洁牙剂中的强效抗细菌剂和抗牙菌斑
本发明人已经发现，本公开的CHC络合物在很大程度上不溶于水，并
因此，本公开提供CHC举身，以及将CHC递送到口腔，即递送到牙齿
本公开的另外适用领域将从下文所提供的详细描述变得显而易见。应理
附图说明
本公开将从详细描述和附图得到更完全的理解，在附图中：
图1描绘了在正离子模式下获取的含氯己定环己基氨基磺酸盐络合物的
图2描绘了在负离子模式下获取的含氯己定环己基氨基磺酸盐络合物的
图3描绘了基于在图2中的m/z：682处表示的母离子的环己基氨基磺
图4描绘了基于在图1中的m/z：684处表示的母离子的环己基氨基磺
图5描绘了基于在图1中的m/z：863处表示的母离子的环己基氨基磺
图6描绘了溶解于氘化DMSO中的氯己定环己基氨基磺酸盐络合物晶
图7描绘了溶解于氘化DMSO中的氯己定环己基氨基磺酸盐络合物晶
图8描绘了图7的放大区段；和
图9描绘了由单晶X射线衍射测量测定的氯己定环己基氨基磺酸盐络合
具体实施方式
以下优选实施例的描述在本质上仅为示例性的，并且决不意图限制所公
因此，在第一实施例中，本公开提供具有式[C22H32Cl2N10][C6H12NO3S]2
1.1.络合物1，其中络合物由呈1∶1到1∶3(例如约1∶2)的氯己定：环己
1.2.络合物1或1.1呈结晶形式。
1.3.前述络合物中的任一者，其中络合物为无水的。
1.4.前述络合物中的任一者，其中络合物呈水合物、半水合物或多水合
1.5.前述络合物中的任一者，其呈水合物形式。
1.6.根据权利要求1.4或1.5所述的络合物，其具有式
1.7.前述络合物中的任一者，其在P21/c空间群中呈结晶形式。
1.8.前述络合物中的任一者，其中氯己定分子中的一个双胍基团与一个
1.9.前述络合物中的任一者，其中氯己定分子中的两个双胍基团与一个
1.10.前述络合物中的任一者，其具有如图9中所示的结构，其中具有
1.11.前述络合物中的任一者，其中氯己定-环己基氨基磺酸盐络合物在
1.12.络合物1.8，其中水溶液含有大于50wt.％水、大于60wt.％水、
1.13.络合物1.8或1.9，其中水溶液含有84wt.％水、3wt.％乙醇和10
1.14.前述络合物中的任一者，其中氯己定-环己基氨基磺酸盐络合物在
1.15.前述络合物中的任一者，当从乙醇水溶液中结晶时。
1.16.前述络合物中的任一者，其在越来越多的水稀释后形成沉淀物。
在另一个实施例中，本公开提供用于向口腔施用的口腔护理组合物(组
2.1组合物2，其中络合物由呈1∶1到1∶3(例如约1∶2)的氯己定：环己
2.2前述络合物中的任一者，其中氯己定-环己基氨基磺酸盐络合物在水
2.3前述络合物中的任一者，当从乙醇水溶液中结晶时。
2.4前述组合物中的任一者，其中CHC为完全或部分地由氯己定和环
2.5前述组合物中的任一者，其包含呈组合物的0.01重量％到40重量％
2.6前述组合物中的任一者，其中组合物呈洁牙剂、凝胶或漱口剂形式。
本公开进一步提供杀灭细菌的方法，其包含使细菌与抗细菌有效量的
本公开进一步提供制造包含CHC(例如络合物1以及下列等等中的任
本公开进一步提供(i)CHC(例如络合物1以及下列等等中的任一者)
应理解，尽管CHC可能主要呈络合物形式，但可以与氯己定和环己基
组合物可以包括CHC(例如络合物1以及下列等等中的任一者)和/或
在某些实施例中，本公开组合物(例如组合物2以及下列等等中的任一
在一些实施例中，组合物中的氯己定的总量为组合物的0.05重量％到
如本文所用，“口腔护理组合物”是指预期用途可以包括口腔护理、口
如本文所用，“口腔可接受的”是指在用于例如漱口剂或洁牙剂的口腔
如本文所用，“口腔可接受的载剂”是指可用于配制本文所公开的口腔
载剂代表除CHC(例如络合物1以及下列等等中的任一者)或氯己定
对于口腔护理组合物，载剂可以为用于洁牙剂和漱口剂的任何载剂。载
可以包括于具有本公开组合物的口腔护理配制物中的任选成分包括溶
组合物可以用于通过将组合物施用到牙齿表面(即使细菌或牙菌斑与组
因此，本公开提供(i)用于杀灭口腔中的细菌的方法，其包含向牙齿施
除非另外说明，否则本说明书中给出的组合物组分的所有百分比均为以
如所属领域中所常见，如本文所提供的组合物和配制物是参照它们的成
实例
实例1-合成氯己定-环己基氨基磺酸盐络合物CHC
根据表1中详述的配方产生水性组合物。观察到氯己定-环己基氨基磺
表1
材料 浓度(wt.％)
氯己定 0.69
环己基氨基磺酸钠 0.09
甘油 9.75
氟化钠 0.05
水 84％
Tween 20 0.30
Mvacide 0.05
木糖醇 2.0
糖精 0.02
乙醇 3.0
薄荷香精 0.05
收集从溶液中沉淀出的晶体，并且对其进行下文详述的进一步分析。
实例2：CHC质谱分析
使用配备有ESI接口和Agilent 1260毛细管LC系统(美国加利福尼亚
在分析期间使用的移动相为甲醇。流动速率为70μL/min并且注射体积
将氯己定-环己基氨基磺酸盐络合物溶解到甲醇中，并且浓度为约200
为了证实加合物存在，在图3、4和5中进行串联质谱实验。在负离子
实例3：CHC的1H NMR分析
对于氘化DMSO溶液中的呈1wt.％浓度的CHC样品执行1H NMR测
1H NMR谱展示于图6中，并且相关COSY序列展示于图7和8中。这
实例4：晶体结构测定
在45kV和35mA下操作的配备有Oxford Cryostream低温装置和细焦
本文所述的数据证实氯己定以使其抗细菌活性最大化的方式从本发明
如通篇所用，范围用作描述介于范围内的每个值的简略表达方式。介于
除非另外规定，否则本文和本说明书中其它处表达的所有百分比和量都
本公开已经参考示例性实施例加以描述。虽然已经示出并描述了几个实

Claims (17)

1.一种氯己定-环己基氨基磺酸盐络合物，其具有式
2.根据权利要求1所述的氯己定-环己基氨基磺酸盐络合物，其呈结晶
3.根据权利要求1所述的氯己定-环己基氨基磺酸盐络合物，其中所述
4.根据权利要求1所述的氯己定-环己基氨基磺酸盐络合物，其中所述
5.根据权利要求4所述的氯己定-环己基氨基磺酸盐络合物，其中所述
6.根据任一前述权利要求所述的氯己定-环己基氨基磺酸盐络合物，其
7.根据权利要求1所述的氯己定-环己基氨基磺酸盐络合物，其在P21/c
8.根据权利要求1所述的氯己定-环己基氨基磺酸盐络合物，其具有其
9.根据权利要求1所述的氯己定-环己基氨基磺酸盐络合物，其在水溶
10.根据权利要求9所述的氯己定-环己基氨基磺酸盐络合物，其中水溶
11.根据权利要求1所述的氯己定-环己基氨基磺酸盐络合物，其中所述
12.一种口腔护理组合物，其包含根据权利要求1所述的氯己定-环己基
13.根据权利要求12所述的口腔护理组合物，其中所述氯己定-环己基
14.根据权利要求12或13所述的口腔护理组合物，其中所述氯己定-
15.根据权利要求12所述的口腔护理组合物，其中所述氯己定-环己基
16.根据权利要求12所述的口腔护理组合物，其中所述组合物呈洁牙
17.一种制造根据权利要求1所述的氯己定-环己基氨基磺酸盐络合物
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MX2020006296A (es) 2020-09-10
US20220192952A1 (en) 2022-06-23
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US11278481B2 (en) 2022-03-22

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Correction item: Claims

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