Evaluation of a low-fluoride anticaries toothpaste containing an innovative calci

描述(由申请人提供)：最近一份关于儿童的临床研究报告发现，尽管在两年的时间里，使用1000ppm F牙膏或400至550ppm F牙膏的两组患者在防龋方面没有统计学差异，但使用低氟牙膏的龋齿发病率有定向上升的趋势。然而，临床数据显示，当使用低氟牙膏时，龋齿进展会随着时间的推移而增加。上面讨论的同一份研究报告还发现，使用1000ppm F牙膏的人的氟斑牙患病率显著高于使用F含量在400 ppm到550 ppm之间的牙膏的人。另外，不希望使用正常的非处方药(OTC)水平的氟化物，但仍希望在较低氟化物的产品中获得相同的(如果不是更好的)防腐益处的成年人目前没有有效的选择。这在普通民众和科学研究人员中仍然是一个非常敏感的问题，事实上，有一本完整的同行评议期刊(氟化物)，其中载有许多关于氟化物产生的不良影响的出版物。在找到有效的替代方案之前，这样的争论和争论将继续下去。简单地增加口腔给药系统(如牙膏)中的氟化物水平并不是解决办法，特别是如果考虑到氟斑牙的潜在风险的话。因此，有机会在不损害牙列健康的情况下提供防腐福利。已发表的研究表明，与单一矿物治疗相比，包括氟、钙和磷在内的多种矿物处理可以协同作用，提供更高的保护水平。超过95%的美国人每天刷牙，牙膏是最广泛使用和接受的局部氟化物治疗形式。为了在不影响防腐效益的情况下降低潜在的氟斑牙风险，开发一种多矿物牙膏配方是可能的，该配方比现有的OTC含氟牙膏含有更低的氟化物水平(即~500ppm F)，如果配方中可以加入其他与氟化物兼容的建牙矿物的话。这种配方将专门针对儿童和成人，作为创造重大价值和提供重大公共卫生惠益的安全和有效的替代方案。印第安纳纳米科技公司拥有一种独特的氟化物兼容功能化磷酸三钙(FTCP)的专利申请技术。在这份SBIR第一阶段提案中，我们以我们目前的知识、经验和fTCP技术的成功为基础，试图确定配制一种低氟加fTCP牙膏的可行性，该牙膏的防腐效果至少与已有的OTC氟化物牙膏一样好。我们已经与FDA批准的符合cGMP的领先牙膏制造商和一所知名大学合作，以满足以下具体目标：1)配制三种牙膏：无氟(安慰剂)；一种含氟化物500ppm；一种含氟化物500ppm加fTCP；2)执行实验室研究，包括FDA推荐的一系列实验室研究，包括氟化物生物利用度、牙釉质氟摄取以及通过remin/demin周期逆转白斑病变；以及3)双盲交叉原位临床研究的临床评估。 与公共健康相关：临床数据显示，当使用含氟量低于非处方(OTC)牙膏(~1100 ppm氟化物)的牙膏时，随着时间的推移，龋齿进展会增加。但儿童和成年人不希望使用非处方药牙膏，但仍然渴望至少相同的，如果不是更好的，从含氟较少的牙膏中受益的防龋剂，目前还没有有效的选择。为了在不影响防腐效益的情况下降低潜在的氟斑牙风险，通过结合Nanotech创新的氟化物兼容建牙矿物质，开发一种与现有OTC氟化物牙膏相比含氟量更低(即~500ppm F)的多矿物牙膏配方是可能的。这种配方将专门针对儿童和成人，作为创造重大价值和提供重大公共卫生惠益的安全和有效的替代方案。

DESCRIPTION (provided by applicant): A recent clinical research report on children found that over a two-year period although there was no statistical differences in anticaries benefits between two groups using either 1000 ppm F or 400 to 550 ppm F toothpastes, there was a directional trend of caries incidence increasing with lower fluoride toothpastes. Nevertheless clinical data demonstrate caries progression increases over time when lower fluoride toothpastes are used. The same research report discussed above also found the prevalence of dental fluorosis was dramatically higher for users of a 1000 ppm F toothpaste compared to users of toothpaste containing between 400 and 550 ppm F. Separately, adults not wishing to use a normal over-the-counter (OTC) level of fluoride but still desiring the same, if not better, anticaries benefits in a product having less fluoride do not currently have an efficacious option. This continues to be a very sensitive issue among the general population as well as scientific researchers, and in fact there exists an entire peer-reviewed journal (Fluoride) that contains many publications on the ill-effects produced by fluoride. Until an effective alternative is found, such contention and debate will continue. Simply increasing the level of fluoride in an oral delivery system, such as toothpaste, is not the answer, especially if one considers the potential risks of dental fluorosis. As such, there is an opportunity to provide anticaries benefits without compromising the health of the dentition. Published studies reveal that multi-mineral treatments, including fluoride, calcium, and phosphorous can act synergistically to provide enhanced levels for protection compared to single mineral treatments. With over 95% of the US population brushing their teeth daily, toothpastes are the most widely used and accepted form of topical fluoride treatment. In order to reduce potential dental fluorosis risks without compromising anticaries benefits, the development of a multi-mineral toothpaste formulation that contains lower levels of fluoride (i.e. ~ 500 ppm F) relative to existing OTC fluoride toothpastes may be possible if other fluoride-compatible tooth-building minerals could be included in the formulation. Such a formulation would be targeted specifically for children and adults as a safe and effective alternative to create significant value and provide a significant public health benefit. Indiana Nanotech has patent-pending technology for a unique fluoride-compatible functionalized tricalcium phosphate (fTCP). By building on our current knowledge, experience, and success with the fTCP technology, in this SBIR Phase I proposal we seek to determine the feasibility of formulating a low fluoride plus fTCP toothpaste that provides anticaries efficacy at least as good as an established OTC fluoride toothpaste. We have partnered with a leading FDA-approved and cGMP compliant dentifrice manufacturer and a renowned university to address the following Specific Aims: 1) Formulation of three toothpastes: fluoride-free (placebo); one with 500 ppm fluoride; one with 500 ppm fluoride plus fTCP; 2) Execution of laboratory studies that include a battery of FDA-recommended laboratory studies, including fluoride bioavailability, enamel fluoride uptake, and white-spot lesion reversal via remin/demin cycling.; and 3) The clinical evaluation in a double-blind cross-over in situ clinical study. PUBLIC HEALTH RELEVANCE: Clinical data demonstrate caries progression increases over time when toothpastes are used containing lower levels fluoride relative to that found in over-the-counter (OTC) toothpaste (~ 1100 ppm fluoride). But children and adults not wishing to use OTC toothpaste but still desiring at least the same, if not better, anticaries benefits from a toothpaste having less fluoride do not currently have an efficacious option. In order to reduce potential dental fluorosis risks without compromising anticaries benefits, the development of a multi-mineral toothpaste formulation that contains lower levels of fluoride (i.e. ~ 500 ppm F) relative to existing OTC fluoride toothpastes may be possible by combining Nanotech's innovative fluoride-compatible tooth-building minerals could be included in the formulation. Such a formulation would be targeted specifically for children and adults as a safe and effective alternative to create significant value and provide a significant public health benefit.