CN114848511A - 一种牙釉质再矿化液及其制备方法与应用 - Google Patents
一种牙釉质再矿化液及其制备方法与应用 Download PDFInfo
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- CN114848511A CN114848511A CN202210636793.0A CN202210636793A CN114848511A CN 114848511 A CN114848511 A CN 114848511A CN 202210636793 A CN202210636793 A CN 202210636793A CN 114848511 A CN114848511 A CN 114848511A
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- water
- oil
- enamel
- phosphate
- soluble
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- Cosmetics (AREA)
Abstract
本发明公开了一种牙釉质再矿化液及其制备方法与应用,具体涉及口腔护理领域。一种牙釉质再矿化液包括:含有可溶性钙盐的水包油包水乳液;含有可溶性磷酸盐的水包油包水乳液;含有可溶性铈盐的水包油包水乳液。本发明的牙釉质再矿化液能够将铈负载于牙釉质上,为牙釉质提供抗酸蚀、抗菌、隔绝环境病毒对人体损伤及抑制牙体、牙龈组织炎症的功效,并且增强牙釉质的再矿化效果。
Description
技术领域
本发明属于日化、口腔硬组织医疗、护理、清洁产品技术领域,具体涉及医疗及口腔清洁护理类产品,更具体地,涉及一种牙釉质再矿化液及其制备方法与应用。
背景技术
人牙釉质富含96%无机羟基磷灰石,研究显示牙釉质中的釉柱呈核壳结构,有机脂质体及其他无机元素主要集中于釉柱的内核中,其壳层结构以无机羟基磷灰石为主。
羟基磷灰石(HAP)是微溶的物质,因此牙体在口腔唾液中存在溶解再矿化过程,通过提供钙、磷离子来实现牙釉质再矿化的方法已经被证实。
通过饮食及细菌所产生的酸性物质容易使牙釉质脱矿,进而形成白斑,最终演化为龋齿;通过添加钙、磷离子可以一定程度上修复受损牙釉质。但是,受牙釉质表面细菌及其形成的细菌膜影响,牙釉质再矿化过程被限制,细菌持续生长,连续产酸,导致最终牙釉质脱矿速率远超再矿化速率,牙齿形成酸蚀。因此有效抑制细菌在牙釉质表面的滋生及在牙体上负载抗酸蚀的物质是有效解决牙釉质酸蚀脱矿的理想策略。
发明内容
为此,本发明提供一种牙釉质再矿化液及其制备方法与应用,以解决现有口腔护理产品对牙釉质再矿化和抗酸蚀效果不佳的问题。
为了实现上述目的,本发明提供如下技术方案:
根据本发明的第一方面提供的一种牙釉质再矿化液,包括:
含有可溶性钙盐的水包油包水乳液;
含有可溶性磷酸盐的水包油包水乳液;
含有可溶性铈盐的水包油包水乳液。
本发明通过采用上述隔室化处理的钙、磷、铈离子为原料,避免应用前离子间直接接触反应,在应用过程中,钙、磷、铈离子在牙釉质表面破乳释放,并以牙体为晶种即时提供钙磷离子形成磷酸钙过饱和溶液促进牙釉质再矿化,同时再矿化过程中铈离子与OH-反应形成牙釉质/氧化铈复合材料。
本发明进一步发现,氧化铈负载于牙釉质上,当缺电子酸性环境形成,氧化铈会放出氧自由基,形成供电子状态,氧自由基与氢离子反应形成中性环境的同时,氧自由基还有一定几率进入产酸细菌体内,杀死产酸细菌,从而对牙釉质形成保护。在碱性条件下,体系呈供电子状态,载铈牙釉质中的铈显示还原性能,能够捕捉引起炎症因子的氧自由基及氮氧自由基,从而更好的保护口腔免除炎症反应。
因此,本发明的牙釉质再矿化液能够将铈负载于牙釉质上,为牙釉质提供抗酸蚀、抗菌、隔绝环境病毒对人体损伤及抑制牙体、牙龈组织炎症的功效,并且增强牙釉质的再矿化效果。
进一步地,所述含有可溶性钙盐的水包油包水乳液的制备方法如下:
将含有可溶性钙盐的水溶液与含有固体粒子的油相按体积比(1-3):(1-19)混合,于温度30-80℃,转速10-24000转/分下搅拌0.5-120分钟,得含有可溶性钙盐的油包水乳液;之后将所述含有可溶性钙盐的油包水乳液与含有固体粒子的水相按体积比(1-3):(1-19)混合,于温度30-80℃,转速10-24000转/分下搅拌0.5-120分钟,得所述含有可溶性钙盐的水包油包水乳液。
需要说明的是,含有可溶性磷酸盐的水包油包水乳液,及含有可溶性铈盐的水包油包水乳液的制备方法与上述含有可溶性钙盐的水包油包水乳液的完全相同,区别仅在于,使用的可溶性盐不同,将上述制备含有可溶性钙盐的水包油包水乳液中使用的可溶性钙盐相应地替换成可溶性磷酸盐,或可溶性铈盐即可制备成含有可溶性磷酸盐的水包油包水乳液,及含有可溶性铈盐的水包油包水乳液。
进一步地,所述含有可溶性钙盐的水溶液中钙离子浓度为0.0001-2.5mol/L。
进一步地,所述含有可溶性磷酸盐的水溶液中磷酸根离子浓度为0.0001-7mol/L。
进一步地,所述含有可溶性铈盐的水溶液中铈离子浓度为0.0001-2mol/L。
进一步地,所述含有固体粒子的油相的制备方法如下:固体微纳米粒子与油脂按质量比(0.1-25):100,于温度30-80℃下混合而成。
进一步地,所述含有固体粒子的水相的制备方法如下:固体粒子与水按质量比(0.1-25):100混合而成。
进一步地,所述可溶性钙盐为能够溶解于水、醇类物质,并能够产生游离态钙离子的物质。作为示例,所述可溶性钙盐包括但不限于氯化钙、氢氧化钙、氧化钙、硝酸钙、葡萄糖酸钙、碳酸氢钙、乳酸钙中的一种或多种。
进一步地,所述可溶性磷酸盐为能够产生游离态磷酸根、磷酸氢根或磷酸二氢根离子的化合物。作为示例,所述可溶性磷酸盐包括但不限于磷酸钾、磷酸钠、磷酸铵、磷酸一氢钾、磷酸一氢钠、磷酸一氢铵、磷酸二氢钾、磷酸二氢钠、磷酸二氢铵中的一种或多种。
进一步地,所述可溶性铈盐为能够溶解于水并能够产生游离态铈离子的物质。作为示例,所述可溶性铈盐包括但不限于氯化铈、硫酸铈、硝酸铈中的一种或多种。
进一步地,所述固体粒子为有机微纳米粒子和/或无机微纳米粒子。作为示例,所述固体粒子包括但不限于碳酸钙、氧化铝、二氧化硅、磷酸钙、硅酸镁铝、木质纤维素、蛋白颗粒中的一种或多种。
进一步地,所述油脂为用于口腔治疗的水剂、凝胶剂、制备牙膏、漱口水或者牙釉质修复凝胶用的所有植物来源、动物来源、矿物来源的天然油脂中、或者以石油化工产品及天然提取原料加工的合成的油脂。作为示例,所述油脂包括但不限于甘油三脂、花生油、菜籽油、猪油、牛油、乳木果油、葵花籽油、核桃油、大豆油中的一种或多种。
根据本发明的第二方面提供的一种如上所述的牙釉质再矿化液的制备方法,将所述含有可溶性钙盐的水包油包水乳液、含有可溶性磷酸盐的水包油包水乳液、含有可溶性铈盐的水包油包水乳液混合即得。
根据本发明的第三方面提供的一种如上所述的牙釉质再矿化液在口腔护理用品中的应用,所述口腔护理用品为牙膏、漱口水或凝胶。
根据本发明的第四方面提供的一种口腔护理用品,包括如上所述的牙釉质再矿化液。
根据本发明的第五方面提供的一种在牙釉质上负载铈的方法,使用如上所述的牙釉质再矿化液或如上所述的口腔护理用品进行日常刷牙,或者,在人工唾液中模拟日常刷牙。
在一些优选的实施例中,通过日常刷牙,在牙釉质再矿化过程中沉积铈元素于牙釉质上,发挥功效。或者通过将离体牙釉质用环氧树脂包埋,暴露釉质面,通过在人工唾液中模拟日常刷牙过程,实现再矿化牙釉质表面载铈。
可以理解的是,为了使铈高效负载在牙釉质上,口腔护理用品中优选含有磨料,比如,二氧化硅或碳酸钙或二水磷酸氢钙。
本发明具有如下优点:
1、本发明通过将水相分别为游离钙离子、磷酸根离子及铈离子的水包油包水乳液按照不同的比例混合,并用牙刷在牙釉质表面破乳,在牙釉质再矿化的过程中,能够将铈元素负载在再矿化牙釉质表面,增强牙齿硬度,同时使氧化铈的抗酸蚀、抗菌、抗炎症等的生物功效应用于人体,更有利于提高牙釉质的再矿化效果。
2、本发明通过在牙釉质表面负载氧化铈的方式使牙釉质具备抗菌、抗炎等功效,避免口服氧化铈带来的肾代谢毒性,安全可靠。
附图说明
为了更清楚地说明本发明的实施方式或现有技术中的技术方案,下面将对实施方式或现有技术描述中所需要使用的附图作简单地介绍。显而易见地,下面描述中的附图仅仅是示例性的,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据提供的附图引伸获得其它的实施附图。
图1为本发明提供的牙釉质模块侧面的透射电镜TEM照片。
图2为本发明提供的样品1的牙釉质表面细菌膜厚度图。
图3为本发明提供的样品2的牙釉质表面细菌膜厚度图。
图4为本发明提供的样品3的牙釉质表面细菌膜厚度图。
具体实施方式
以下由特定的具体实施例说明本发明的实施方式,熟悉此技术的人士可由本说明书所揭露的内容轻易地了解本发明的其他优点及功效,显然,所描述的实施例是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
实施例1
制备含有可溶性钙盐的水包油包水乳液:
1)将8g碳酸钙加入到200g甘油三脂中,搅拌均匀制得油相备用;将10g碳酸钙加入到200g水中,加热至60℃,搅拌均匀制得水相备用。
2)将120ml钙离子浓度0.5mol/l的氯化钙水溶液加入到200ml油相中,加热至80℃,用高速分散机以2000转/分搅拌5分钟,得含有可溶性钙盐的油包水乳液;
3)将100ml水包油包水乳液加入到200ml水相中,加热至40℃,用高速分散机以3000转/分搅拌3分钟,得含有可溶性钙盐的水包油包水乳液。
制备含有可溶性磷酸盐的水包油包水乳液:
1)将100g二氧化硅加入到1000g花生油中,搅拌均匀制得油相备用;将160g碳酸钙加入到2000g水中,加热至50℃,搅拌均匀制得水相备用。
2)将100ml磷酸根离子浓度0.3mol/l的磷酸钾水溶液加入到300ml油相中,加热至45℃,用高速分散机以5000转/分搅拌2分钟,得含有可溶性磷酸盐的油包水乳液;
3)将200ml水包油包水乳液加入到600ml水相中,加热至40℃,用高速分散机以3000转/分搅拌3分钟,得含有可溶性磷酸盐的水包油包水乳液。
制备含有可溶性铈盐的水包油包水乳液:
1)将100g碳酸钙加入到1000g甘油三脂中,搅拌均匀制得油相备用;将160g碳酸钙加入到2000g水中,加热至60℃,搅拌均匀制得水相备用。
2)将100ml铈离子浓度0.15mol/L的氯化铈水溶液加入到300ml油相中,加热至45℃,用高速分散机以4000转/分搅拌3分钟,得含有可溶性铈盐的油包水乳液;
3)将100ml水包油包水乳液加入到300ml水相中,加热至45℃,用高速分散机以2000转/分搅拌2分钟,得含有可溶性铈盐的水包油包水乳液。
本实施例提供的牙釉质再矿化液的制备方法如下:
将上述制备的含有可溶性钙盐的水包油包水乳液、含有可溶性磷酸盐的水包油包水乳液、含有可溶性铈盐的水包油包水乳液按体积比5:3:2混合。
实施例2
制备含有可溶性钙盐的水包油包水乳液:
1)将20g硅酸镁铝加入到200g大豆油中,搅拌均匀制得油相备用;将20g硅酸镁铝加入到300g水中,加热至45℃,搅拌均匀制得水相备用。
2)将100ml钙离子浓度1mol/L的硝酸钙水溶液加入到350ml油相中,加热至50℃,用高速分散机以5000转/分搅拌3分钟,得含有可溶性钙盐的油包水乳液;
3)将200ml水包油包水乳液加入到400ml水相中,加热至60℃,用高速分散机以3000转/分搅拌3分钟,得含有可溶性钙盐的水包油包水乳液。
制备含有可溶性磷酸盐的水包油包水乳液:
1)将20g二氧化硅加入到250g花生油中,搅拌均匀制得油相备用;将30g碳酸钙加入到400g水中,加热至50℃,搅拌均匀制得水相备用。
2)将100ml磷酸根离子浓度0.6mol/L的磷酸氢二钾水溶液加入到350ml油相中,加热至50℃,用高速分散机以5000转/分搅拌5分钟,得含有可溶性磷酸盐的油包水乳液;
3)将100ml水包油包水乳液加入到300ml水相中,加热至40℃,用高速分散机以3000转/分搅拌5分钟,得含有可溶性磷酸盐的水包油包水乳液。
制备含有可溶性铈盐的水包油包水乳液:
1)将10g碳酸钙加入到200g甘油三脂中,搅拌均匀制得油相备用;将30g碳酸钙加入到500g水中,加热至60℃,搅拌均匀制得水相备用。
2)将100ml铈离子浓度1mol/L的氯化铈水溶液加入到200ml油相中,加热至60℃,用高速分散机以5000转/分搅拌5分钟,得含有可溶性铈盐的油包水乳液;
3)将100ml水包油包水乳液加入到200ml水相中,加热至60℃,用高速分散机以4000转/分搅拌4分钟,得含有可溶性铈盐的水包油包水乳液。
本实施例提供的牙釉质再矿化液的制备方法如下:
将上述制备的含有可溶性钙盐的水包油包水乳液、含有可溶性磷酸盐的水包油包水乳液、含有可溶性铈盐的水包油包水乳液按体积比5:3:3混合。
实施例3
制备含有可溶性钙盐的水包油包水乳液:
1)将20g碳酸钙加入到200g甘油三脂中,搅拌均匀制得油相备用;将20g碳酸钙加入到200g水中,加热至30℃,搅拌均匀制得水相备用。
2)将100ml钙离子浓度0.8mol/L的氯化钙水溶液加入到400ml油相中,加热至70℃,用高速分散机以4500转/分搅拌4分钟,得含有可溶性钙盐的油包水乳液;
3)将150ml水包油包水乳液加入到600ml水相中,加热至55℃,用高速分散机以3000转/分搅拌3分钟,得含有可溶性钙盐的水包油包水乳液。
制备含有可溶性磷酸盐的水包油包水乳液:
1)将20g二氧化硅加入到200g花生油中,搅拌均匀制得油相备用;将35g碳酸钙加入到500g水中,加热至40℃,搅拌均匀制得水相备用。
2)将100ml磷酸根离子浓度1mol/L的磷酸氢二钾水溶液加入到400ml油相中,加热至50℃,用高速分散机以3000转/分搅拌4分钟,得含有可溶性磷酸盐的油包水乳液;
3)将150ml水包油包水乳液加入到450ml水相中,加热至60℃,用高速分散机以2000转/分搅拌3分钟,得含有可溶性磷酸盐的水包油包水乳液。
制备含有可溶性铈盐的水包油包水乳液:
1)将20g碳酸钙加入到200g甘油三脂中,搅拌均匀制得油相备用;将30g碳酸钙加入到400g水中,加热至40℃,搅拌均匀制得水相备用。
2)将100ml铈离子浓度1mol/L的氯化铈水溶液加入到300ml油相中,加热至45℃,用高速分散机以4000转/分搅拌4分钟,得含有可溶性铈盐的油包水乳液;
3)将200ml水包油包水乳液加入到400ml水相中,加热至50℃,用高速分散机以3000转/分搅拌5分钟,得含有可溶性铈盐的水包油包水乳液。
本实施例提供的牙釉质再矿化液的制备方法如下:
将上述制备的含有可溶性钙盐的水包油包水乳液、含有可溶性磷酸盐的水包油包水乳液、含有可溶性铈盐的水包油包水乳液按体积比8:5:2混合。
对比例1
本对比例提供的牙釉质再矿化液与实施例1的区别仅在于,不包括含有可溶性铈盐的水包油包水乳液。
试验例1
将30g实施例1的牙釉质再矿化液添加到120g云南白药冬青美白牙膏中,混合均匀。
采用上述牙膏对牙釉质模块进行刷试,每天3次,每次3分钟,15天后,采用共聚焦离子束(FIB)对牙釉质模块进行切割,牙釉质模块侧面的透射电镜TEM照片见图1。
从图1中可以看到,在牙釉质表面沉积氧化铈(黑色)和再矿化的羟基磷灰石(灰白色)的复合物。
试验例2
牙膏样品的制备:
牙膏样品1:在100g市售牙膏(纯青普洱牙膏,云南白药)中加入0.01mol/L的盐酸2滴约0.3ml,混合均匀;
牙膏样品2:在100g牙膏样品1中加入实施例3的牙釉质再矿化液15ml;
牙膏样品3:在100g牙膏样品1中加入对比例1的牙釉质再矿化液15ml。
对市售牙膏及牙膏样品1-3的pH值进行测试,结果见表1。
表1
样品 | pH值 |
市售牙膏 | 7.6 |
牙膏样品1 | 5.5 |
牙膏样品2 | 7.0 |
牙膏样品3 | 6.1 |
由表1可见,本发明提供的牙釉质再矿化液可以快速改变体系的酸性环境,从而减少酸性物质对牙釉质的影响。
将相同表面暴露的牙釉质用环氧树脂包埋后置于2g牙膏样品中,并加入10ml水,刷试3分钟,静置2小时,加入20g水进行稀释,离心分离出上清液,用离子色谱测量上清液中钙离子浓度。测试结果见表2。
表2
样品 | 钙离子浓度 |
牙膏样品1 | 0.14mmol/l |
牙膏样品2 | 0.04mmol/l |
牙膏样品3 | 0.06mmol/l |
由表2可见,采用牙膏样品2进行刷试的牙膏上清液中钙离子浓度显著低于其他牙膏样品,说明本发明的牙釉质再矿化液能够增强牙膏的抗酸蚀性能,促进牙釉质再矿化。
试验例3
抑制蛀牙菌(变异量球菌)实验
将试验例2实验组样品1、样品2和样品3刷试后的牙釉质模块分别置于24孔组织培养板的孔中(每孔中一个模块,模块不可接触孔壁),37℃用正常人体除菌唾液(1.0mL/孔)包衣4h,1.0mL PBS冲洗2次。在37℃接种两代至生长对数期(菌液浓度107cfu/mL)的变异链球菌,培养24h形成生物膜。
将牙模块依次用1.0mL无菌PBS(每次漂洗的浸泡时间,10s)冲洗2-3次,以除去非黏附细菌;使用安装在无振动平台上的488nm Ar/Ar-Kr激光扫描头的TCSSP2共聚焦显微镜进行非侵入式共聚焦成像。使用的物镜是40×,图像三倍放大;样本进行LIVE/DEAD染色使用RBacLightTM细菌活力试剂盒。染色时间为(9±1)min,染色比例为1∶1,获得在相应波长[Syto9:515nm~530nm;碘化丙啶(PI):>600nm]下的最佳荧光信号;选择覆盖有生物膜的牙模块上至少3个独立且具有代表性的位置进行这些测量。在每个区域内,通过确定生物膜的上限和下限来测量最厚的点。样品1的牙釉质细菌膜厚度图见图2所示;样品2的牙釉质细菌膜厚度图见图3所示;样品3的牙釉质细菌膜厚度图见图4所示。
从图2、图3和图4的生物膜厚度来看,样品1因为受到酸蚀的牙釉质表面吸附更多的细菌,导致细菌膜厚度较大,样品2中细菌膜厚度最小,且出现不同的颜色,说明变异链球菌在牙釉质表面死亡,导致细菌膜厚度变小,再矿化后牙釉质表面粗糙度减小,所吸附的变异链球菌也减少了,导致细菌膜厚度相较于样品1减小;样品3的细菌膜厚度也比样品1小,但是比样品2大,说明样品3仅使牙釉质表面受损部位修复,降低了对变异链球菌的吸附,但是并没有抑制变异链球菌的滋生,因此细菌膜厚度比样品2较厚;因此铈元素的负载除了能显著降低生物膜厚度外,还导致大量的变异链球菌出现了死亡,效果相对于样品2及样品1较好。
虽然,上文中已经用一般性说明及具体实施例对本发明作了详尽的描述,但在本发明基础上,可以对之作一些修改或改进,这对本领域技术人员而言是显而易见的。因此,在不偏离本发明精神的基础上所做的这些修改或改进,均属于本发明要求保护的范围。
Claims (10)
1.一种牙釉质再矿化液,其特征在于,包括:
含有可溶性钙盐的水包油包水乳液;
含有可溶性磷酸盐的水包油包水乳液;
含有可溶性铈盐的水包油包水乳液。
2.根据权利要求1所述牙釉质再矿化液,其特征在于,所述含有可溶性钙盐/磷酸盐/铈盐的水包油包水乳液的制备方法如下:
将含有可溶性钙盐/磷酸盐/铈盐的水溶液与含有固体粒子的油相按体积比(1-3):(1-19)混合,于温度30-80℃,转速10-24000转/分下搅拌0.5-120分钟,得含有可溶性钙盐/磷酸盐/铈盐的油包水乳液;之后将所述含有可溶性钙盐/磷酸盐/铈盐的油包水乳液与含有固体粒子的水相按体积比(1-3):(1-19)混合,于温度30-80℃,转速10-24000转/分下搅拌0.5-120分钟,得所述含有可溶性钙盐/磷酸盐/铈盐的水包油包水乳液。
3.根据权利要求2所述牙釉质再矿化液,其特征在于,
所述含有可溶性钙盐的水溶液中钙离子浓度为0.0001-2.5mol/L;
和/或,所述含有可溶性磷酸盐的水溶液中磷酸根离子浓度为0.0001-7mol/L;
和/或,所述含有可溶性铈盐的水溶液中铈离子浓度为0.0001-2mol/L。
4.根据权利要求3所述牙釉质再矿化液,其特征在于,
所述可溶性钙盐选自氯化钙、氢氧化钙、氧化钙、硝酸钙、葡萄糖酸钙、碳酸氢钙、乳酸钙中的一种或多种;
和/或,所述可溶性磷酸盐选自磷酸钾、磷酸钠、磷酸铵、磷酸一氢钾、磷酸一氢钠、磷酸一氢铵、磷酸二氢钾、磷酸二氢钠、磷酸二氢铵中的一种或多种;
和/或,所述可溶性铈盐选自氯化铈、硫酸铈、硝酸铈中的一种或多种。
5.根据权利要求2所述牙釉质再矿化液,其特征在于,
所述含有固体粒子的油相的制备方法如下:固体粒子与油脂按质量比(0.1-25):100,于温度30-80℃下混合而成;
和/或,所述含有固体粒子的水相的制备方法如下:固体粒子与水按质量比(0.1-25):100混合而成。
6.根据权利要求5所述牙釉质再矿化液,其特征在于,
所述固体粒子选自碳酸钙、氧化铝、二氧化硅、磷酸钙、硅酸镁铝、木质纤维素、蛋白颗粒中的一种或多种;
和/或,所述油脂选自甘油三脂、花生油、菜籽油、猪油、牛油、乳木果油、葵花籽油、核桃油、大豆油中的一种或多种。
7.权利要求1-6任一项所述的牙釉质再矿化液的制备方法,其特征在于,将所述含有可溶性钙盐的水包油包水乳液、含有可溶性磷酸盐的水包油包水乳液、含有可溶性铈盐的水包油包水乳液混合即得。
8.权利要求1-6任一项所述的牙釉质再矿化液在口腔护理用品中的应用,其特征在于,所述口腔护理用品为牙膏、漱口水或凝胶。
9.一种口腔护理用品,其特征在于,包括权利要求1-6任一项所述的牙釉质再矿化液。
10.一种在牙釉质上负载铈的方法,其特征在于,使用权利要求1-6任一项所述的牙釉质再矿化液制备而成的口腔护理用品或使用权利要求9所述的口腔护理用品进行日常刷牙,或者,在人工唾液中模拟日常刷牙。
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