CN111417603A - 生物活性硼酸盐玻璃及其方法 - Google Patents
生物活性硼酸盐玻璃及其方法 Download PDFInfo
- Publication number
- CN111417603A CN111417603A CN201880077025.8A CN201880077025A CN111417603A CN 111417603 A CN111417603 A CN 111417603A CN 201880077025 A CN201880077025 A CN 201880077025A CN 111417603 A CN111417603 A CN 111417603A
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- Prior art keywords
- composition
- glass
- bioactive
- borate glass
- mole
- Prior art date
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- Granted
Links
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- 238000000034 method Methods 0.000 title claims abstract description 26
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- KKCBUQHMOMHUOY-UHFFFAOYSA-N Na2O Inorganic materials [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 claims abstract description 11
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Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C03—GLASS; MINERAL OR SLAG WOOL
- C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
- C03C4/00—Compositions for glass with special properties
- C03C4/0007—Compositions for glass with special properties for biologically-compatible glass
- C03C4/0021—Compositions for glass with special properties for biologically-compatible glass for dental use
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- A61K6/802—Preparations for artificial teeth, for filling teeth or for capping teeth comprising ceramics
- A61K6/818—Preparations for artificial teeth, for filling teeth or for capping teeth comprising ceramics comprising zirconium oxide
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- A61K6/831—Preparations for artificial teeth, for filling teeth or for capping teeth comprising non-metallic elements or compounds thereof, e.g. carbon
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- A—HUMAN NECESSITIES
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- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
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Abstract
生物活性硼酸盐玻璃组合物,其包含例如:30至60%B2O3,0.5至20%ZrO2,3至30%Na2O,0.1至15%K2O,0.1至15%MgO,5至30%CaO,和1至5%P2O5,以摩尔%计,以总组成为100摩尔%计。还公开了组合物以及生物活性硼酸盐玻璃牙本质治疗制剂的制造方法和使用方法。
Description
本申请根据35U.S.C.§119,要求2017年11月28日提交的美国临时专利申请第62/591,429号的优先权,其全文通过引用结合入本文。
相关申请的交叉引用
本申请涉及共同拥有且转让的USSN申请第62/342,384号(题为“BIOACTIVEALUMINOBORATE GLASSES(生物活性铝硼酸盐玻璃)”,2016年5月27日提交),以及第62/342,411号(题为“BIOACTIVE GLASS MICROSPHERES(生物活性微球体)”,2016年5月27日提交),但是没有要求它们的优先权。
本申请还涉及如下共同拥有且转让的USSN申请:
2017年11月28日提交的第62/591,423号,题为“BIOACTIVE GLASS COMPOSITIONSAND METHODS OF TREATING DENTIN HYPERSENSITIVITY(生物活性玻璃组合物以及牙本质超敏性治疗方法)”;
2017年11月28日提交的第62/591,446号,题为“HIGH LIQUIDUS VISCOSITYBIOACTIVE GLASS(高液相线粘度生物活性玻璃)”;以及
2017年11月28日提交的第62/591,438号,题为“CHEMICALLY STRENGTHENEDBIOACTIVE GLASS-CERAMICS(化学强化生物活性玻璃陶瓷)”,它们与本申请同时提交,但是本申请没有要求它们的优先权。
本文所述的出版物或专利文献的全文内容分别通过参考结合于本文。
背景技术
本公开内容涉及玻璃组合物、生物活性玻璃组合物,以及该组合物的制造和使用方法。
发明内容
在实施方式中,本公开内容提供了生物活性硼酸盐玻璃组合物,其包含例如:30至60%B2O3,0.5至20%ZrO2,3至30%Na2O,0.1至15%K2O,0.1至15%MgO,5至30%CaO,和1至5%P2O5,以摩尔百分比表示,基于总组成的100摩尔%计,其是例如:不含Al2O3、不含SiO2或不含它们的混合物。
在实施方式中,本公开内容提供了生物活性硼酸盐玻璃组合物,其包含例如:30至60%B2O3,0.5至20%ZrO2,3至30%Na2O,0.1至15%K2O,5至30%CaO,和1至5%P2O5,以摩尔百分比计,基于总组成的100摩尔%计,其是例如:不含Al2O3、SiO2、MgO或者它们的混合物。
在实施方式中,所揭示的生物活性硼酸盐玻璃组合物展现出优异的生物适应性。
在实施方式中,本公开内容提供了生物活性硼酸盐玻璃组合物和制剂,其堵塞速率相比于例如牙本质治疗实验中的含生物活性45S5玻璃配方是两倍那么快。
在实施方式中,本公开内容提供了用于治疗牙本质超敏性的制剂和方法。
附图说明
在本公开内容的实施方式中:
图1A至1F显示七天(7天)周期上的来自活细胞/死细胞化验的细胞形态的光学图像。
图2显示实施例组合物1的ATP化验。
图3A至3D显示具有不同处理的测试牙本质盘的SEM显微镜图。
具体实施方式
下面参考附图(如果有的话)对本公开内容的各个实施方式进行详细描述。参考各个实施方式不限制本发明的范围,本发明的范围仅受所附权利要求书的范围限制。此外,在本说明书中列出的任何实例都不是限制性的,并且仅列出了要求保护的本发明的诸多可能的实施方式中的一些实施方式。
在实施方式中,所揭示的组合物、制品以及制造和使用方法提供了一个或多个优势特征或方面,包括例如,如下文所述。任意权利要求所陈述的特征或方面一般在本发明的所有方面适用。在任一项权利要求中所陈述的任意单个或多个特征或方面可以结合或与任一项或多项其它权利要求中所述的任意其它特征或方面结合或置换。
定义
“牙本质超敏性”(DH)“牙本质敏感性”(DS)或者类似术语指的是由于冷热、空气、触摸或者化学或渗透刺激物(例如甜食)导致的短暂刺痛。
“遮挡”,“堵塞”,“遮蔽”或者类似术语指的是例如封闭或堵塞至阻塞。
“玻璃(glass)”“玻璃(glasses)”或者类似术语可以表示玻璃或玻璃陶瓷。
“玻璃制品”或者类似术语可以表示整体或部分由玻璃或玻璃陶瓷制造的任意物体。
“香料”“调味剂”或者类似术语可以表示当用户与组合物接触时,为所公开的组合物提供感官性质的任何天然或合成物质。香料可以是例如单种化合物或者化合物的混合物。可以对香料进行选择,从而给予组合物或产品独特的香味或者维持不同产品批次之间或者配方改变之后的香味一致性。香料可以是任何已知或发现的化合物,例如:二乙酰基,乙酰丙酰基,乙偶姻,乙酸异戊酯,苯甲醛,肉桂醛,丙酸乙酯,邻氨基苯甲酸甲酯,柠檬烯,癸二烯酸乙酯(ethyl decadienoate),己酸烯丙酯,乙基麦芽酚(ethyl maltol),乙基香兰素,水杨酸甲酯,以及类似化合物或其混合物。
本领域技术人员已知的其他典型组合物组分或制剂成分例如研磨剂、湿润剂、着色剂、抗菌剂、表面活性剂、增白剂、粘合剂以及类似组分或成分参见例如en.wikipedia.org/wiki/Toothpaste。
“包括”、“包含”或类似术语意为包括但不限于,即内含而非排他。
本文所述的实施方式中用来对例如组合物中成分的量、浓度、体积、加工温度、加工时间、产率、流速、压力、粘度和类似数值及其范围或者组件的尺寸以及类似数值及其范围进行修饰的“约”是指可能发生的数值量的改变,例如,源自制备材料、组合物、复合体、浓缩物、组件部件、制品制造或使用制剂所用的常规测量和操作过程;源自这些过程中的偶然性误差;源自用来实施所述方法的起始材料或成分的制造、来源或纯度的差异;以及类似因素。术语“约”还包括由于具有特定初始浓度或混合物的组合物或制剂的老化而不同的量,以及由于混合或加工具有特定初始浓度或混合物的组合物或制剂而不同的量。
“任选的”或“任选地”指的是随后描述的事件或情况可能发生或可能不发生,描述内容包括事件或情况发生的场合以及事件或情况没有发生的场合。
除非另有说明,否则,本文所用的不定冠词“一个”或“一种”及其相应的定冠词“该”表示至少一(个/种),或者一(个/种)或多(个/种)。
可以采用本领域技术人员熟知的缩写(例如,表示小时的“h”或“hrs”;表示克的“g”或“gm”;表示毫升的“mL”;表示室温的“rt”;表示纳米的“nm”以及类似缩写)。
在组分、成分、添加剂、尺寸、条件、时间和类似方面公开的具体和优选的数值及其范围仅用于说明;它们不排除其他限定数值或限定范围内的其他数值。本公开内容的组合物和方法可包括本文所述的任何数值或数值、具体数值、更具体的数值和优选数值的任何组合,包括明示或暗示的中间值和范围。
生物活性玻璃具有广泛认可的促进骨细胞生长,并且与硬组织和软组织强烈结合的能力。还报道生物活性玻璃释放了激活成骨基因表达的离子和刺激血管生成(参见Rahaman等人,“Bioactive glass in tissue engineering(组织工程学中的生物活性玻璃)”,Acta Biomater,2011,7:2355-2373)。基于硅酸盐玻璃的牙膏(例如和)可以与唾液反应并释放钙、磷酸根或氟化物离子,从而在暴露的牙本质上以及在牙本质细管内形成羟基碳酸磷灰石或氟磷灰石(参见Kulal,“An in-vitro comparisonof nano hydroxyapatite,Novamin and Proargin desensitizing toothpastes-a SEMstudy(纳米羟基磷灰石、Novamin和Proargin脱敏牙膏的体外对比,SEM研究)”,J ClinDiagn Res,2016,10(10):ZC51–ZC54;L.J.Litkowski的题为“Compositions containingbioactive glass and their use in treating tooth hypersensitivity(含生物活性玻璃的组合物以及他们在治疗牙齿超敏性中的应用)”的US6338751;以及Hill的题为“Bioactive glass composition(生物活性玻璃组合物)”的US 9168272)。
使用含生物活性玻璃的牙膏进行治疗是能够提供长期牙本质保护(例如,数个月)的方法。不同于牙本质细管的其他遮蔽试剂,所揭示的生物活性玻璃制剂可以提供长期治疗。
由于它们的新颖性质(例如,快速分解和转化为羟基磷灰石状材料、支持血管生成和软组织的再生)(参见上文Rahaman等人),对于生物活性硼酸盐玻璃的兴趣不断增长。但是,硼快速释放到溶液中会导致降低的细胞存活能力,特别是对于体外细胞培养而言。可以通过例如对玻璃组成进行改性以包含一些二氧化硅或者通过在动态环境中培养细胞来解决这个细胞存活能力问题(参见上文的Rahaman)。来自康宁有限公司的某些铝硼酸盐玻璃已经证实具有例如优异的生物相容性、增强的血管生产以及促进伤口愈合(参见例如上文提到的共同拥有的USSN 62/342,384、62/342,411以及(尚未转让的)_______())。但是,在这些含Al2O3的生物活性玻璃中,出于神经细胞毒性考虑,铝离子的释放是潜在的问题。已经在硅酸盐玻璃中加入ZrO2改善了玻璃耐久性(参见Simhan,“Chemical durability of ZrO2 containing glasses(含ZrO2玻璃的化学耐久性)”J Non-Cryst Solids,1983,54:335-343)。但是,不清楚ZrO2对于基于不含硅酸盐的硼酸盐玻璃的生物相容性的影响。
在实施方式中,本公开内容提供了基于硼酸盐玻璃的一组玻璃组合物,其具有优异的生物相容性。此外,所揭示的玻璃组合物能够堵塞住牙本质细管,暗示了在牙本质超敏性治疗中的应用。
在实施方式中,本公开内容提供了含ZrO2的硼酸盐玻璃组合物,其展现出优异的生物相容性并且其可以用于治疗牙本质超敏性。
在实施方式中,以摩尔百分比表示,玻璃包含:30至60%B2O3,0.5至20%ZrO2,3至30%Na2O,0.1至15%K2O,0.1至15%MgO,5至30%CaO,和1至5%P2O5。表1列出了示例性组合物和对照样。这些玻璃通常可以在低于例如1300℃的温度下熔化,在某些实施方式中低于1200℃,这使得可以在较小的商用玻璃罐中熔化组合物。
在实施方式中,出乎意料地发现向硼酸盐玻璃添加ZrO2改善了硼酸盐玻璃组合物的生物相容性。相比于不含ZrO2的对比硼酸盐玻璃(例如,对比对照组合物2)(图1),在所揭示的玻璃组合物(例如,所揭示的实施例组合物1)中看到明显更多的存活细胞数量(参见表1)。在4天之后,对比硼酸盐玻璃碟上没有存活的细胞,而在所揭示的含ZrO2的组合物中,细胞计数持续增加。采用ATP试验证实了所揭示的组合物中的持续细胞生长(图2)。所揭示的玻璃组合物的优异的生物相容性归结于其较低的硼离子释放速率,相信这是由于在组合物中加入或者存在ZrO2所导致的。
在实施方式中,所揭示的组合物可以与唾液反应并释放钙、磷酸根或氟化物离子,从而形成羟基碳酸磷灰石(图3)或氟磷灰石,通过在牙本质细管内和在表面处形成涂抹层展现出细管遮蔽,并且重建、强化和保护了牙齿结构。氟化物离子可以以前体形式(例如,氟化钠(NaF)、氟化亚锡(SnF2)、氟化钙(CaF2)或其混合物)结合到玻璃组合物中,它的量是例如1至25摩尔%,以组合物的超添加计。
在实际口腔流体中,预期结合了氟化物的玻璃释放出氟化物并形成氟磷灰石,它比羟基碳酸磷灰石(HCA)甚至更加耐酸溶解。
在实施方式中,可以通过各种已知技术,将所揭示的玻璃加工成例如粉末、短纤维、珠、片材、3D支架和类似形状因子。例如,通常可以通过玻璃料的喷射研磨或球磨来制备玻璃粉末。可以通过熔纺或电纺来制造短纤维。例如,可以通过使得玻璃颗粒流动通过垂直炉来制造珠。例如,可以采用薄辊制、浮法或熔合拉制工艺来制造片材。例如,可以通过快速成型、聚合物泡沫复制以及颗粒烧结和类似方法来制造支架。例如,合乎希望的玻璃形式可以被用于支撑细胞生长、软组织和硬组织再生、模拟基因表达或者血管新生。
玻璃的生物相容性和分解受到相应的玻璃组成的影响。在所揭示的玻璃组合物中,B2O3作为主要的形成玻璃的氧化物。硼酸盐玻璃远没有硅酸盐玻璃那么耐用,这使得它对于快速降解具有吸引力。但是,降解导致的毒性以及降解速率的控制仍然是一个难题。
P2O5也起到网络形成剂的作用。此外,磷酸根离子释放到生物活性玻璃的表面会对形成磷灰石做出贡献。通过生物活性玻璃提供磷酸根离子增加了磷灰石的形成速率以及骨组织的结合能力。此外,P2O5增加了玻璃的粘度,这进而扩大了操作温度范围,并且因而对于制造和形成玻璃是有利的。
除了其作为网络形成剂或前体玻璃中的中间体的角色之外,ZrO2改善了硼酸盐玻璃中的化学耐久性,同时没有毒性问题。
碱性氧化物(即,Li2O、Na2O、K2O、Rb2O和Cs2O)对于实现低熔融温度和低液相线温度起了助剂的作用。据报道添加碱性氧化物改善了生物活性(参见上文的Rahaman等人)。
二价阳离子氧化物(例如,碱土氧化物)也可以改善玻璃的熔融行为和生物活性。具体来说,发现当浸入模拟体液(SBF)或者在体内时,CaO与P2O5反应形成磷灰石。从玻璃表面释放的Ca2+离子对形成富集了磷酸钙的层起到贡献。
在实施方式中,本公开内容提供了生物活性硼酸盐玻璃组合物,其包含:
30至60%B2O3;
0.5至20%ZrO2;
3至30%Na2O;
0.1至15%K2O;
0.1至15%MgO;
5至30%CaO;以及
1至5%P2O5,以摩尔%计,以总组成为100摩尔%计。
源的摩尔%具有如下等价重量%:30至60%B2O3,0.5至20%ZrO2,3至30%Na2O,0.1至15%K2O,0.1至15%MgO,5至30%CaO,和1至5%P2O5,以重量%计,以总组成为100重量%计。
在实施方式中,上文所述生物活性硼酸盐玻璃组合物不含Al2O3,不含SiO2,或者不含它们的混合物。
在实施方式中,上文所述的生物活性硼酸盐玻璃组合物还可以包含例如选自下组的氟化物离子源,例如:氟化钠(NaF)、氟化亚锡(SnF2)、氟化钙(CaF2)以及类似氟化物离子源,或其混合物。
在实施方式中,本公开内容提供了生物活性硼酸盐玻璃组合物,其包含:
30至60%B2O3;
0.5至20%ZrO2;
3至30%Na2O;
0.1至15%K2O;
5至30%CaO;以及
1至5%P2O5,以摩尔%计,以总组成为100摩尔%计。
源的摩尔%具有如下等价重量%:30至60%B2O3,0.5至20%ZrO2,3至30%Na2O,0.1至15%K2O,5至30%CaO,和1至5%P2O5,以重量%计,以总组成为100重量%计。
在实施方式中,上文所述的生物活性硼酸盐玻璃组合物不含MgO。
在实施方式中,上文所述生物活性硼酸盐玻璃组合物不含Al2O3,不含SiO2,不含MgO,或者不含它们的混合物。
在实施方式中,上文所述的生物活性硼酸盐玻璃组合物还可以包含选自下组的氟化物离子源:氟化钠(NaF)、氟化亚锡(SnF2)、氟化钙(CaF2)以及类似氟化物离子源,或其混合物。
在实施方式中,本公开内容提供了治疗牙本质超敏性的方法,包括:使得具有至少一种牙本质超敏现象的牙齿样品的至少一个表面与包含任意所揭示的组合物的制剂接触。
在实施方式中,可以在例如至少一天1的时间零点完成接触。
在实施方式中,可以在例如对于1至12周的时间段,每天1至10次完成接触。
本公开内容具有如下数方面的优势,包括例如:
出乎意料地发现所揭示的含ZrO2的硼酸盐玻璃组合物具有优异的生物相容性,以及
相比于已知的硅酸盐玻璃组合物,所揭示的含ZrO2的硼酸盐玻璃组合物具有出乎意料的更快的牙本质细管堵塞速率。
参见附图,图1A至1F显示七天(7天)周期上的来自活细胞/死细胞化验的细胞形态的光学图像。在24孔培养板中,在组合物1的玻璃碟(12.5mm直径乘2.0mm厚)上完成细胞培养。在初始颜色图像中(未提供),绿色图像点(用实心点描绘)表示存活细胞,以及红点(用空心点描绘)表示死细胞。将对比组合物(即,对照样1(45S5))(图1A至1C)和实施例组合物1(图1D至1F)用于细胞形态研究。
图2显示实施例组合物1的ATP化验。使用ATP化验来确定所揭示的组合物在哺乳动物细胞中的细胞增殖和细胞毒性。在24孔培养板中,在组合物1的玻璃碟(12.5mm直径乘2.0mm厚)上完成细胞培养。(在第一天、第4天和第7天结束时测得的)读数发光越高,则细胞数量越多。
图3A至3D显示具有如下不同处理的测试牙本质盘的SEM显微镜图:没有任意处理的对照牙本质盘(未处理,3A);用牙膏基础制剂(即,仅有载剂)处理1周的牙本质盘(3B);用含45S5(对比对照样1)的牙膏处理1周的牙本质盘(3C);以及用所揭示的含实施例组合物1的牙膏处理1周的牙本质盘(3D)。在处理期间,将所有的样品浸入人造唾液中。对于牙膏基础制剂(3B),牙本质细管没有遮蔽。在用含45S5的牙膏处理之后,一半的牙本质细管被晶体状沉淀物遮蔽(3C)。在用含实施例组合物1的牙膏处理之后,所有的牙本质细管和牙本质表面都被晶体状沉淀物遮蔽(3D)。
表1列出了示例性的含ZrO2硼酸盐玻璃组合物和对照组合物1和2。
表1:含ZrO2的硼酸盐玻璃组合物和对照样
对每种牙科制剂,评估由人体臼齿制造的牙本质盘的遮蔽能力,如表2所示。
表2:基础牙膏组合物和含示例性生物活性玻璃的牙膏组合物
用于生产本发明的玻璃组合物的原材料和/或设备会引入某些不是故意添加的杂质或组分,并且它们会存在于最终的玻璃组合物中。此类材料会在玻璃组合物中以少量存在,并且本文称作“杂物”。
所揭示的玻璃组合物通常会以痕量包含杂物。类似地,“不含铁”、“不含钠”、“不含锂”、“不含锆”、“不含碱土金属”、“不含重金属”或者类似表征表示组合物没有故意添加杂物,但是组合物仍然可能包含铁、钠、锂、锆、碱土金属或者重金属等,但是是近似痕量或者痕量。
除非另有说明,否则本文所引用的所有组分的浓度是以重量百分比(重量%)表示。
虽然会用过渡语“包括”来描述特定实施方式的各种特征、元素或步骤,但是在替代实施方式中,这包含了那些可以采用过渡语由“......构成”、“基本由......构成”描述在内的替代实施方式。
实施例
以下实施例示范了根据上文一般程序制造、使用和分析所揭示的组合物、制剂和方法。
实施例1
玻璃制备,通过如下制备表1中的实施例1的组合物:将批料源材料以所示量混合,包括硼酸、碳酸钠、碳酸钾、石灰石、氧化镁、磷酸钙和锆石。使用Turbula混合器,在塑料广口瓶中对批料原材料进行剧烈的混合。然后将混合物转移到内部体积约为650cc的铂坩锅中。然后将坩埚装载到退火炉中,在250℃煅烧批料24小时。然后经煅烧的批料在1100至1300℃熔化6小时,然后将玻璃熔体倒到钢板上,以及在400至500℃退火。
实施例2
牙科制剂,以例如如下方式分别制备表2的牙科制剂:首先将丙三醇和PEG400添加到表1中的实施例1的玻璃组合物(具有通过喷射研磨产生的1至10微米的粒度),然后添加制剂中余下成分并用刮刀进行彻底混合。
实施例3
牙科制剂的评估,通过如下方式对实施例2中提及的牙科制剂进行评估:通过合法方式从bforbones公司(bforbones.com)购得人体臼齿。使用Buehler低速水冷金刚石锯,在牙骨质-牙釉质接合面上方垂直于牙齿的长轴切割厚度为1mm的牙本质盘。用500目砂纸打磨30秒,在牙本质盘的两侧产生涂抹层。后续通过用6%柠檬酸处理3小时然后用水冲洗以及37℃干燥,来去除该涂抹。将牙本质盘随机分成对照组或实验组,每组含有至少3个样品试样,其接收非水性牙膏基础制剂(空白)或含有5%45S5的牙膏(对照组成1);以及含有所揭示的玻璃组合物的牙膏,如表1和表2所列。使用牙膏和电动牙刷来刷牙本质盘的两侧,每侧持续1分钟。然后,用蒸馏水冲洗试样以去除可见的痕量牙膏,然后储存在人造唾液中(1.5mM CaCl2,0.9mM KH2PO4,130mM KCl,和20mM HEPES,pH 7.4)。刷、冲洗和每个试样储存在人造唾液中的过程每天重复2次持续7天,然后试样在37℃干燥16小时,以及在SEM之前储存在RT。
已经参考各种具体实施方式和技术描述了本公开内容。然而,应理解的是,可进行多种变动和修改,这仍然保持在本公开内容的范围之内。
Claims (12)
1.一种生物活性硼酸盐玻璃组合物,其包含:
30至60%B2O3;
0.5至20%ZrO2;
3至30%Na2O;
0.1至15%K2O;
0.1至15%MgO;
5至30%CaO;以及
1至5%P2O5,以摩尔%计,以总组成为100摩尔%计。
2.如权利要求1所述的生物活性硼酸盐玻璃组合物,其中,组合物不含Al2O3、SiO2或其混合物。
3.如权利要求1或2所述的生物活性硼酸盐玻璃组合物,其还包括选自NaF、SnF2、CaF2或其混合物的氟化物离子源,它的量是1至25摩尔%,以组合物的超添加计。
4.一种生物活性硼酸盐玻璃组合物,其包含:
30至60%B2O3;
0.5至20%ZrO2;
3至30%Na2O;
0.1至15%K2O;
5至30%CaO;以及
1至5%P2O5,以摩尔%计,以总组成为100摩尔%计。
5.如权利要求4所述的生物活性硼酸盐玻璃组合物,其中,组合物不含Al2O3,不含SiO2,不含MgO,或者不含它们的混合物。
6.如权利要求4或5所述的生物活性硼酸盐玻璃组合物,其还包括选自NaF、SnF2、CaF2或其混合物的氟化物离子源,它的量是1至25摩尔%,以组合物的超添加计。
7.一种牙本质超敏性的治疗方法,其包括:
使得具有至少一种牙本质超敏性现象的牙齿样品的至少一个表面与包含权利要求1-3中任一项的组合物的制剂接触。
8.如权利要求7所述的方法,其中,接触是在至少一天1的时间零点完成。
9.如权利要求7或8所述的方法,其中,接触的完成是如下方式:每天1至10次,持续1至12周的时间段。
10.一种牙本质超敏性的治疗方法,其包括:
使得具有至少一种牙本质超敏性现象的牙齿样品的至少一个表面与包含权利要求4-6中任一项的组合物的制剂接触。
11.如权利要求10所述的方法,其中,接触是在至少一天1的时间零点完成。
12.如权利要求10或11所述的方法,其中,接触的完成是如下方式:每天1至10次,持续1至12周的时间段。
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US20190161392A1 (en) | 2019-05-30 |
WO2019108557A1 (en) | 2019-06-06 |
US11198638B2 (en) | 2021-12-14 |
TW201929828A (zh) | 2019-08-01 |
EP3717428A1 (en) | 2020-10-07 |
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