氟化物疗法
![]() 氟化钠锭剂。锭剂是最不受推荐的氟化物疗法(相较于局部使用的氟化物疗法,例如含氟牙膏、漱口水、涂料等,使用锭剂的效果较差)。 | |
临床资料 | |
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商品名 | OrthoWash、PerioMed及其他 |
AHFS/Drugs.com | Monograph |
核准状况 | |
给药途径 | 口服给药 |
ATC码 | |
法律规范状态 | |
法律规范 | |
识别信息 | |
CAS号 | 7681-49-4 |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
化学信息 | |
化学式 | FNa |
摩尔质量 | 41.99 g·mol−1 |
3D模型(JSmol) | |
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为达到医疗目的,会使用氟化物进行治疗,此种程序称为氟化物疗法(英语:fluoride therapy)。[2]在饮用水含氟量不足的地区,为预防年龄在6个月以上儿童出现龋齿(蛀牙),专家建议为其补充氟化物。[3]补充方式通常是口服液体、药丸的方式,或是使用含氟牙膏来刷牙。[4]氟化物也曾应用于治疗多种骨骼疾病。[5]
婴幼儿若摄取相对较高剂量的氟化物,会在牙齿上留下白色斑点,此称为氟斑症。[4]如过量摄取更会导致严重的氟斑症,牙齿呈棕色或黄色、变得脆弱易断,严重情况下甚至会引发急性中毒。氟化物疗法通常采用氟化钠的形式,但也会使用氟化亚锡的形式。[4][5]氟化物的作用机制是减少酸对牙齿的侵蚀、促进牙齿再矿化,并降低细菌的活性。[5]氟化物主要透过直接接触牙齿后来发挥功效。[3][5]
医界在1940年代开始用氟化物来预防龋齿。[6]氟化物已列入世界卫生组织基本药物标准清单之中。[7]它于2021年是美国排名第291位最常开立的药物,处方笺的数量超过60万张。[8][9]
医疗应用
[编辑]预防龋齿
[编辑]氟化物疗法在预防龋齿方面能产生正面功效。[10]浓度达到或超过1,000ppm(百万分之一) 的含氟牙膏,能有效降低学龄儿童与青少年罹患龋齿的风险。[10]当乳齿仍在发育时,摄取氟化物能让牙齿结构更强健,更能抵抗蛀蚀,然而这也会提高罹患氟斑症的几率。[10][11][12]经氟化处理过的饮用水与牛奶是两种有效的全身性氟化物疗法,有助于预防龋齿发生。[13]
骨质疏松症
[编辑]科学界曾针对女性更年期(停经)后可能出现的骨质疏松症而研究以补充氟化物的方式进行治疗,但目前看来并无显著疗效。虽然氟化钠能提升骨骼密度,却无法有效降低发生骨折的风险。[14][15]
副作用
[编辑]氟斑症
[编辑]未满6岁的儿童使用浓度达到或超过1,000ppm的含氟牙膏以及氟化物补充剂,特别是在出生后3年内使用,与较高的氟斑症风险有关联。[10]个体于孕期最后6个月补充氟化物,对儿童氟斑牙的发生率并无显著影响。[16]为预防龋齿而进行的最佳饮用水氟化处理,会使牙齿氟斑症的盛行率增加4%至5%。[13]观察到的影响多为轻微至中等程度,通常对美观影响甚微。[13]
其他风险
[编辑]过量摄取
[编辑]大量摄取氟化物可能导致氟中毒,甚至致死。估计对于大多数成年人而言,致死剂量为5至10克,相当于每公斤体重32至64毫克的元素氟。[17][18][19]即使摄取低至每公斤体重0.2毫克的氟化物,也可能引发肠胃不适,这个剂量远低于致死剂量的20倍。[20]长期摄取及局部接触可能造成牙齿氟斑症,而过度的全身性暴露则可能导致骨骼氟斑症。美国牙科协会 (ADA) 建议采母乳哺育为主,以减少婴儿的氟化物摄取量,并预防他们出现氟斑症。[21]
于1974年,美国有一名3岁孩童初次就诊牙医时,误食45毫升、浓度为2%的氟化物溶液(剂量是致死量的3倍)后不幸身亡。牙科诊所于事后被判定需为死亡事件负责。[22]
作用机转
[编辑]确切地说,氟化物疗法的作用是修复,而非预防牙齿损伤,它促使氟磷灰石这种矿物质整合到受损的牙釉质(也称珐琅质)中。虽然在鲨鱼的牙齿中可找到氟磷灰石,但它并非人类牙齿的天然组成部分。人类天然牙釉质的主要矿物质是羟磷灰石,而非在有氟化物存在时形成的氟磷灰石。即使没氟化物,牙齿中的矿物质含量也会根据口腔的酸碱度以及口腔内其他物质(例如磷酸盐和钙)的浓度而呈现波动式增减。
氟化物借由形成氟磷灰石,并融入牙齿的牙釉质,来减少牙釉质腐蚀。氟离子能减缓牙釉质中矿物质流失,并在龋齿初期促进牙齿再矿化。氟化物正是透过这种脱矿化与再矿化的循环过程来发挥保护作用。[23]对于预防龋齿非常重要的再矿化循环,必须在口腔内有氟化物存在时才会发生。一旦氟化物被吞咽,其效用便极为微弱。[10][24][25]
目前有关氟化物对口腔微生物群的影响,以及此影响对于氟化物整体抗龋齿效果的重要性,科学界尚未达成共识。[23][24]
氟化物可透过许多化学方法传递(氟化钠、氟化亚锡、胺化氟、单氟磷酸钠等等)。研究显示,这些不同化学形式的氟化物在抗龋齿效果上的差异,不如个人在刷牙、使用氟化物产品以及使用后的行为差异来得显著。通常氟化物的化学形式取决于与其他混合元素的相容性、价格以及其他因素。[23]
所有氟化方式都会在唾液中释放低浓度的氟离子,进而对牙菌斑内的液体产生局部作用。[26]氟化物并非直接阻止龋齿发生,而是减缓其发展的速度,因此,为使其有效发挥作用,需要全天持续接触。[23]氟离子的供应越稳定,在预防龋齿的效果就越好。[23][24]
施用
[编辑]饮水加氟
[编辑]饮用水加氟是一种受控的过程,将氟化物添加到公共供水系统中,可降低饮用者发生龋齿的几率。[27]美国在1940年代开始推行这项措施,其依据是对一个天然水源富含氟的地区儿童所进行研究的结果。
牙膏
[编辑]目前,估计美国约有3分之2的人口透过公共供水系统来使用加氟的饮水,[28]而全球约有5.7%的人口使用加氟饮水。[29]
估计在饮用水中加氟,每花费一美元,就能节省7至42美元的牙科治疗费用。[30]
市面上常见的牙膏大多含有浓度介于0.22%(相当于1,000ppm)到0.312%(相当于1,450ppm)的氟化物,其形式通常为氟化钠、氟化亚锡或单氟磷酸钠(MFP)。
经常使用含氟量1,100ppm的牙膏,能有效促进牙齿牙釉质的再矿化,并抑制牙釉质及牙根表面的矿物质流失。[31]
为去除较顽固的残渣和轻微的牙齿表面染色,大多数含氟牙膏都添加温和的研磨剂。[32]这些研磨成分包括碳酸钙、硅胶、碳酸镁和磷酸盐等。[32]
市面上亦有含氟牙膏是以0.454%氟化亚锡 (SnF2) 的形式存在,其氟离子浓度为1,100ppm。研究显示,牙膏中的氟化物与锡离子 (Sn2+) 结合后,似乎能为口腔健康带来更广泛的益处。
相较于其他含氟牙膏,含有氟化亚锡的牙膏已被证实能更有效地减少龋齿、[33]牙齿酸蚀、[34][35][36][37]牙龈病、[38][39][40][41][42]牙本质过敏症、[43]牙菌斑、[39][42]牙结石[44]以及牙齿染色[44]等问题。
漱口水
[编辑]含氟漱口水可由牙科专业人员执行涂抹,或供居家使用。漱口水中最常见的含氟成分是中性氟化钠。其浓度范围通常介于0.05%至0.2%(相当于225至1,000ppm的氟离子)。[45]浓度为0.05%的漱口水适用于每日使用,而浓度为0.2%的漱口水则适用于每周使用,以及在学校推行的每周漱口计划。[46]然而对于龋齿高风险族群而言,这些浓度的氟化物强度可能不足。在指导下规律使用每日型(230ppm)或每周型(900ppm)的含氟漱口水,能有效降低儿童恒牙的龋齿发生率。[47]
市面上有许多品牌的局部用氟化物产品贩售。[48]如果个体饮用的水中已含有足够的氟化物,则不建议使用这类漱口水产品。[48]
凝胶/泡沫
[编辑]市面上有多种专业使用的氟化物凝胶和泡沫产品。专业使用的氟化物凝胶种类包括2.0%中性氟化钠和1.23%酸性磷酸氟化钠。[46]
接受头颈部放射治疗的个体,其唾液腺细胞可能会受损害,进而造成口干症状。唾液分泌量减少时,发生龋齿的风险也会随之升高。对于正在进行或已完成头颈部放射治疗的患者,以及唾液分泌不足的患者,建议使用个人化的牙托居家涂抹1.1%的氟化物凝胶。[49]
至于氟化物凝胶在治疗初期性龋齿病灶方面的效果,目前仍需更多研究加以验证。[50]
氟化物涂料
[编辑]相较于氟化物凝胶,氟化物涂料在施用便利性以及所需氟化物用量较少方面具有实际优势。氟化物涂料的原理是将极高浓度(约50,000ppm)的氟化物盐涂抹于牙齿表面。[51]
目前尚无已发表的证据指出,由专业人员涂抹的氟化物涂料会增加牙釉质氟斑症的风险。这种涂料是以刷子涂抹,且能在数秒内快速凝固。
研究显示氟化物涂料能有效减少乳齿和恒齿的早期龋齿病变。[50]对于儿童和青少年而言,每隔6个月涂抹一次氟化物涂料,能有效地预防乳齿和恒齿发生蛀蚀。[52]
缓释装置
[编辑]有一种能缓慢释放氟化物的装置,可植入牙齿表面,通常选择在臼齿的侧面,以避免影响美观和进食。这类装置主要分为两种:共聚物薄膜式和玻璃珠式。它们能有效提高局部氟化物浓度并预防蛀牙,然而,其有固位性不佳,容易脱落的问题。[53]
含氟锭
[编辑]含氟锭剂通常每颗约含1毫克氟化物,使用方法是将其含在口中慢慢吮吸。溶解后的锭剂会逐渐被吞咽,因此,使用含氟锭同时具有局部和全身性的治疗效果。早在1955年,一项比较含氟锭与含氟药丸效果的研究就明确指出,氟化物主要透过局部作用来发挥功效。[24][54]
医疗补充品
[编辑]医疗用的氟化物补充品,如锭剂、口含锭或液体(包括含氟维生素),主要提供给居住在饮用水未加氟地区的儿童。然而,现有证据对于这类补充品在保护乳齿方面的效果较为薄弱。尽管如此,这些补充品能有效预防恒齿蛀蚀,但常见的副作用是轻微至中度的牙齿氟斑症。[10]此外,根据一份系统综述,显示并无证据显示孕妇每日补充氟化物能有效预防其生出子女发生蛀牙或导致氟斑牙。[55]
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延伸阅读
[编辑]- Committee on Fluoride in Drinking Water, National Research Council. (2006). Fluoride in Drinking Water: A Scientific Review of EPA's Standards. National Academies Press.
- Government guidelines
- Fluoride History – History of fluoride therapy including early patents