CN1803147B - 缓冲剂对牙菌斑酸化的作用 - Google Patents
缓冲剂对牙菌斑酸化的作用 Download PDFInfo
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Abstract
本发明提供了一种通过防止在口中形成酸化溶液从而预防或治疗龋齿的Trim水配方。Trim水(碱性)被用作甜食后的漱口水,它可以中和牙菌斑的多种酸并提高牙齿的再钙化。这样,用Trim水漱口基本是可以预防牙齿发生龋齿。可以用许多剂型提供Trim水,比如漱口水和可饮用的饮料。
Description
本案是申请日为2002年12月11日、发明名称为“缓冲剂对牙菌斑酸化的作用”的母案的分案申请。
1.相关技术的对照
本申请要求提交于2001年12月11日的序列号为60/340,769的在先申请的优先权,在此并入以供参考。
2.发明领域
本发明提供了一种通过防止在口中形成酸化溶液从而预防或治疗龋齿的Trim水配方。可以漱口水和可饮用剂型的形式提供Trim水以治疗龋齿。
3.相关技术
龋齿(蛀牙)是一种非常普通的口腔疾病。龋齿通常以白色白垩样区域出现在牙釉质上。这发生在有微生物斑的牙齿上。食物中可发酵的碳水化合物(如糖类)被牙斑菌代谢成酸类(如乳酸),这使牙齿表面的pH值发生变化。如果pH足够低且没有被中和,牙齿(主要含有像羟磷灰石之类的磷酸钙晶体)就会溶解或脱钙,从而产生龋齿。如果在早期没有对牙齿进行处理,它就会向牙髓发展,这就需要大范围的处理以保住牙齿。
高糖饮食增加了牙齿腐烂的危险。仅仅吃了一颗糖之后,一些牙齿表面就会发生脱钙,当如果酸在食用糖后的短时间内(40-60分钟之内)被中和,就可以避免这种危险(再钙化)。这种中和或缓冲可在牙菌斑中由产氨菌的自然发生。如果经常食用糖,尤其是经常吃甜食的儿童,牙菌斑pH的中和以及再钙化就不会发生。如果后面的过程持续几个月牙齿就会生洞。经常食用甜食还会使牙菌斑中的微生物向更加生酸和耐酸的种类转变。通常将5.5或更低的pH值作为脱钙作用的临界点。
限制饮食中糖分的摄取可以降低龋齿的发病几率。然而,这对于喜欢糖类的儿童是非常困难的。另一种方法是在进糖之后中和牙菌斑。这已有过试验性的实验,方法是让个体在吃糖后咀嚼无糖的香口胶,这在理论上刺激了唾液的流动并增加了唾液重碳酸盐(唾液中主要的缓冲盐)的浓度。这增加了唾液流量且咀嚼活动还帮助清除口腔中糖的浓度。用这种方法降级龋齿发生已有报道(Scheinin,Acta OdontScan 33:267,1975)。然而,在进糖之后咀嚼香口胶有时并不适用,且香口胶需要咀嚼一段时间之后在能增加唾液流量。
发明概要
本发明提供了一种通过防止在口中形成酸化溶液从而预防或治疗龋齿的Trim水配方。Trim水(碱)被用作甜食后的漱口水,它可以中和牙菌斑的多种酸并提高牙齿的再钙化。这样,用Trim水漱口基本是可以预防牙齿发生龋齿。可以用许多剂型提供Trim水,比如漱口水和可饮用的饮料。
Trim水可被配置在防治龋齿的制剂中以靠近牙齿施用。Trim水可以是酸性或碱性的。在牙齿附近区域使用的时间可以是约1分钟。例如漱口水可漱洗约1分钟。较好的,本发明的漱口水或饮料能将牙齿附近的pH值保持在5.5左右。
通过以下对本发明的描述可以更加全面的了解本发明这些目的以及其它的目的,这里还附有参考附图和权利要求书。
附图简述
通过下面给出的详细的描述可以更全面的了解本发明,所给出的附图仅仅是为了阐述而不是限制本发明,其中:
图1显示了在含有5%蔗糖的淡水或Trim水中链球菌突变体的pH反应。
图2显示了用水冲洗一分钟之后#26牙齿的pH反应
图3显示了用Trim水冲洗一分钟之后#26牙齿的pH反应
图4显示了用水冲洗一分钟之后#27牙齿的pH反应
图5显示了用Trim水冲洗一分钟之后#27牙齿的pH反应
图6显示了用水冲洗一分钟之后#28牙齿的pH反应
图7显示了用Trim水冲洗一分钟之后#28牙齿的pH反应
图8显示了用水冲洗一分钟之后#29牙齿的pH反应
图9显示了用Trim水冲洗一分钟之后#29牙齿的pH反应
图10显示了在含有5%蔗糖的Trim水中#26牙齿的pH反应。
图11显示了在含有5%蔗糖的Trim水中#27牙齿的pH反应
图12显示了在含有5%蔗糖的Trim水中#28牙齿的pH反应
图13显示了在含有5%蔗糖的Trim水中#29牙齿的pH反应
图14A-14L显示了暴露在链球菌突变体和干乳酪杆菌中的牙齿的一系列X射线照片。
优选实施例的详细描述
本申请中所使用的“Trim”或“Trim水”可交换使用。另外,Trim水在美国专利5,938,915中有描述,在描述如何制造酸性或碱性形式的Trim水时,将其全文并入以供参考。
一种制造Trim水的方法包括以下步骤:提供一带有阳极的阳极室和带有阴极的阴极室的电解水的装置,其中用隔膜将两室分隔开,并在阳极室和阴极室中引入原料水,每对电极上施加的电流约0.16mA/cm2-3.2mA/cm2,将阳极和阴极之间的隔膜保持约0.5秒-5秒以电解原料水,然后从阳极室中取出电解的水,这样就可以获得Trim水。
一种情况下,电流的范围可以在约0.224mA/cm2-1.6mA/cm2之间。另一实施方案中,提取的电离水可被煮沸或进一步过滤。Trim水、煮沸和过滤过的水都包括在内,只要这些水经过上述电流处理即可。
在另一个实施方案中,提取的电解水可被煮沸或进一步过滤。Trim水、煮沸和过滤过的水都包括在内,只要这些水经过上述电流处理即可。这样,Trim水就富含电子。
下面描述了评价Trim水缓冲潜能的实验和用体外生龋牙菌斑进行的三个实验。实验的设计是为检测作为1)进糖后的漱口水;2)甜饮料的基质;和3)对付龋齿的抗龋剂的Trim的抗龋潜能。
在体内将Trim水暴露在含有重碳酸盐缓冲体系的人唾液中,在冲洗不同时间后测量Trim水的pH值(表1)。用酸性或碱性的Trim水冲洗3分钟后,唾液缓冲盐的pH从11.2(碱性)或2.94(酸性)变化到了6-7之间。用1分钟的较短时间冲洗后,即便有蔗糖存在,碱性Trim的pH仍保持在9以上。
使用龋齿模型实验可以看到本发明方法的以下优点。
1.用碱性Trim水冲洗1分钟可快速缓冲暴露在蔗糖中的实验性的龋齿牙菌斑。pH可在5.5(这通常被认为是牙釉质开始脱钙的pH以上)保持至少25分钟。通常,许多含有糖的食品或饮料可在25分钟之内从口中清除。用水冲洗不能提供足够的抗酸作用(图2-9)。
2.与含有蔗糖的水相比,Trim加蔗糖可将pH值在5.5以上保持至少25分钟。当用水冲洗1分钟将Trim和蔗糖同牙菌斑上清除之后,pH可继续在5.5以上保持25分钟。水加蔗糖不能将牙菌斑的pH保持在保护范围之内。
3.用Trim漱口不能在活性实验性龋齿的范围(一般保持在pH4左右)内大大改变pH。
因此,经常让口腔暴露在饮料或漱口水形式的Trim中可以起到预防龋齿的作用,尤其是在进糖后立即使用。
因此,将Trim作为糖饮料的基质要比以水为基质要好。然而,由于在将Trim从口中清除之后会有一些残留的糖类的生龋作用,或被脱氧缓冲,建议将其用在无糖饮料中。这样就不会有发生龋齿了,并且,由于碱性的pH提高了牙齿的再钙化作用,它还可以产生抗龋作用。
然而,用Trim来抑制活性龋齿或在病变区域内防止生酸似乎不可能。
提供以下实施例仅仅是为了阐述本发明而不是限制。
实施例
实施例1.Trim水在暴露在蔗糖中的链球菌突变体上的作用
这一实施方案的目的是确定Trim是否可以降低链球菌突变体的生酸作用。
作为对照,将洗过的链球菌突变体细胞(GEM)(造成人龋齿的主要病原体)在含有5%蔗糖的水中温育35分钟。用pH计检测pH的改变。将同样数量的细胞在含有5%蔗糖的Trim水中温育35分钟并检测pH。
在暴露在链球菌突变体35分钟之内,含有5%蔗糖的水的pH从5.02下降到了4.06。含有5%Trim水的pH从10.4降到了9.15。后者的pH范围仍在牙齿的完整性范围之内。(脱钙化通常在pH5.5以下发生)
实施例2.在体内用Trim或Trim和蔗糖漱口
这一实施例的目的是:1)在含和不含蔗糖的情况下测试Trim对口腔pH的作用,以及2)确定Trim是否可以长时间缓冲唾液菌的生酸。
在体内用含有10%蔗糖的Trim漱口3分钟,然后将其吐在容器中,并将其在37℃下温育110分钟。用pH计检测pH。用同样的方法检测含有10%蔗糖的水的对照溶液。
在体内用Trim分别漱口5、10、15和30秒钟。每次漱口后都将其吐到容器中并测量pH。用水进行同样的实验。
在体内用含有10%蔗糖的Trim分别漱口5、10、15和30秒钟。每次漱口后都将其吐到容器中并测量pH。用水进行同样的实验。
在体内用含有10%蔗糖的Trim漱口3分钟后pH从10.33(Trim和蔗糖的原始pH值)降到到了6.25。将吐出的含有唾液的漱口水在37℃下温育110分钟后,pH降到到了5.59。
用含有10%蔗糖的水进行同样的实验,在体内漱口3分钟后,pH从5.61改变到了6.45。将吐出的漱口水温育110分钟后,pH从6.45降到了5.95。
用酸性Trim重复同样的实验,漱口3分钟后pH从2.94改变到5.45,将吐出的漱口水温育110分钟后pH变为5.53。
这些数据显示了当将Trim在口中保持3分钟时唾液强烈的缓冲潜能。当用Trim短时间(最多1分钟)漱口时,pH仍然较高(表1)
表1.在体内用20mlTrim溶液或水溶液漱口
实施例3.体外龋齿模型
根据龋齿模型系统(Minah,Pediat.Dent 20:345,1998),将在乳牙中提取的牙冠装载在丙烯酸基座中,并将其制成适合放在数字X射线照相装置(可对连续照射精确定位)夹具的形状。在牙釉质上覆盖一层冷处理的丙烯酸后,用#330旋转牙钻在牙齿上钻一个直径为1.0mm的圆孔使牙质暴露。将其在链球菌突变体GEM、I生物型临床分离物(S.m.)和干乳酪杆菌(ATCC11578)(L.c.)中暴露6周就会导致龋齿样病变,采用以下方法:将装载的牙齿放在和S.m.一起温育的含有5.0%蔗糖w/v的脑心浸液肉汤(BHI;Difco,Detroit,MI)中。每天更换培养基并在含有10%CO2的空气中与37℃下温育7天。第8天时,将装载的牙齿放在和L.c.一起温育的含有5.0%蔗糖的MRS肉汤(Difco)中。每天用0.85%的NaCl(生理盐水)和5.0%w/v蔗糖的溶液代替培养基。再培育97天。用连续X射线照相评价龋齿增加的过程。对病变进行点微生物培养。
将牙齿和生龋细菌的纯培养物一起温育105天。随着时间的推移,龋齿样病变出现在牙齿上(图14A-14L)。
实施例4.用Trim或水冲洗1分钟对实验性牙菌斑生酸的影响(间接测量牙菌斑的pH)见图2-9
这一实验的目的是在用Trim冲洗1分钟后模拟对牙菌斑的生酸的作用。
从温育培养基中取出带有生龋牙菌斑牙菌斑的装载的牙齿,并用0.85%的盐溶液(生理盐水)冲洗以除去基质并使糖酵解停止。然后将装载的牙齿在含5%蔗糖的2ml水中于37℃下温育25分钟。这一过程模拟了典型的接触生龋基质的饮食。其间用带有Ross结合微电极(Orion,Fisher)的pH计(Orion 420A,Fisher Scientific)测量水的pH值。然后将牙齿在Trim(试验溶液)或水(对照溶液)中浸泡1分钟,然后将它们放在2ml水中并继续检测pH值25分钟。
在含5%蔗糖的水中暴露了25分钟的牙菌斑的pH从约6.5降低至4.00。用水冲洗1分钟后,pH回到了约5.00并在温育25分钟之后又回落到4.00。
用Trim冲洗1分钟后,pH升高到约7.5并在温育25分钟之后又回落到约5.5。
冲洗一分钟后,Trim对生龋牙菌斑显然有保护作用,这是因为酸度立即升高到安全的水平且它在临界的pH5.5以上保持25分钟以上。
实施例5.含5%蔗糖的Trim或水对实验性生龋牙菌斑生酸作用的影响(间接测量牙菌斑的pH)见图10-13
这一实验的目的是检验当暴露在含有生龋基质的Trim中时牙菌斑的生酸作用。
将实施例2中所述的步骤重复,不同的是,第一次温育时,用含有5%蔗糖的Trim代替含有5%蔗糖的水。然后将所有的牙齿用水冲洗1分钟并在随后的25分钟内检测pH值。
当将含有5%蔗糖的Trim和生龋牙菌斑一起温育25分钟后,pH从约10.0降低到6.2。当在水中继续温育25分钟后在用水冲洗1分钟,pH继续降低到约5.0。
这些结果证明,如果Trim是甜饮料(例如)的基底,当Trim饮料在口中存在时牙菌斑的pH不会降低到生龋的水平。然而,在用水冲洗或可能吞下后,牙菌斑的生酸作用就会继续。
实施例6.用Trim或水冲洗1分钟对实验性牙菌斑生酸作用的影响(直接测量牙菌斑的pH)
这一实验的目的是在用Trim冲洗1分钟后模拟对牙菌斑的生酸的作用。
将实施例2中所述的步骤重复,不同的是,用微电极(Wpi公司,MEPH-3接触微电极,Londonderry,NH)直接测量牙菌斑的pH值。
在这一实验中,在实验性病变中直接测量pH。在和5%蔗糖温育25分钟其间,pH只有些许下降,从约4.2降至4.0。用Trim冲洗1分钟后,4颗牙齿中有3颗的pH升至约7.00,并在第二次温育25分钟后降至约4.5。当用对照溶液水冲洗牙菌斑,并温育25分钟后,pH保持在约4.00。这一实验似乎证明,Trim缓冲液在深度龋齿病变中不是非常有效。结果如下(表2)。
表2.用Trim或水冲洗1分钟对人造龋齿病变生酸作用的影响
在此全文并入所引用的所有的参考资料都以供参考。
精通这一技术的技术人员应认识到,或用常规的实验即可确定,有许多实例与这里详细描述的本发明的特定实施方案是等同的。这些等同的实例应理解为包含在以下权利要求的范围之内。
Claims (4)
1.一种含有电解水的溶液在制备防止牙齿发生龋齿的药物中的用途,其中所述的含有电解水的溶液与牙齿表面接触,所述电解水的氧化还原电势在-150至0mV的范围内;
所述电解水是由这样的方式制成的Trim水:提供一个带有阳极的阳极室和带有阴极的阴极室的电解水的装置,其中用隔膜将两室分隔开,并在阳极室和阴极室中引入原料水,每对电极上施加的电流为0.16mA/cm2-3.2mA/cm2,将阳极和阴极之间的隔膜保持约0.5秒-5秒,以电解原料水,然后从阳极室中取出电解水。
2.如权利要求1所述的用途,其中所述溶液和牙齿表面至少接触1分钟。
3.如权利要求1所述的用途,其中所述溶液使牙齿表面的pH升高至5.5以上。
4.一种含有电解水的溶液在制备防止牙齿发生龋齿的药物中的用途,其中所述的含有电解水的溶液接触牙齿表面,使牙齿表面的pH升至5.5以上,所述电解水的氧化还原电势在-150至0mV的范围内;
所述电解水是由这样的方式制成的Trim水:提供一个带有阳极的阳极室和带有阴极的阴极室的电解水的装置,其中用隔膜将两室分隔开,并在阳极室和阴极室中引入原料水,每对电极上施加的电流为0.16mA/cm2-3.2mA/cm2,将阳极和阴极之间的隔膜保持约0.5秒-5秒,以电解原料水,然后从阳极室中取出电解水。
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