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

含有创新钙的低氟防龋牙膏的评价

• 批准号: 7924998
• 负责人: ROBERT L KARLINSEY
• 金额: $ 20.48万
• 依托单位: INDIANA NANOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-25 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7924998
• 关键词: 2 year old; 5 year old; Acquired Dental Fluorosis; Address; Adult; Age; American; Bioavailable; Biological Availability; Calcium Fluoride; Centers for Disease Control and Prevention (U.S.); Child; Clinical; Clinical Data; Clinical Research; Color; Cyclic GMP; Dental; Dental Enamel; Dental Schools; Dental caries; Dentifrices; Dentition; Development; Double-Blind Method; Drug Formulations; Esthetics; Europe; Evaluation; FDA approved; Fluorides; General Population; Genetic Crossing Over; Goals; Gold; Health; Health Benefit; Health Sciences; In Situ; Incidence; Indiana; Journals; Knowledge; Laboratories; Laboratory Study; Lead; Legal patent; Lesion; Life; Manufacturer Name; Marketing; Minerals; Nanotechnology; Oral; Oral cavity; Oral health; Peer Review; Performance; Pharmacologic Substance; Phase; Phosphorous; Placebos; Population; Porosity; Preschool Child; Prevalence; Prevention; Primary Dentition; Public Health; Publications; Publishing; Relative (related person); Reporting; Research; Research Personnel; Risk; Science; Small Business Innovation Research Grant; System; Technology; Test Result; Texas; Therapeutic; Time; Tooth structure; Toothpaste; Topical Fluorides; Universities; Varnish; White Spots; anticaries; base; drinking water; experience; federal poverty level; improved; innovation; prospective; public health relevance; remin-demin; research clinical testing; research facility; statistics; success; trend; tricalcium phosphate; uptake

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.

描述（申请人提供）：最近一项针对儿童的临床研究报告发现，在两年的时间里，尽管使用含氟1000 ppm或400 - 550 ppm牙膏的两组之间的防龋效果没有统计学差异，但含氟量较低的牙膏的龋齿发病率有增加的趋势。然而，临床数据表明，当使用低氟牙膏时，龋齿的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，与含氟400至550 ppm牙膏的使用者相比，含氟1000 ppm牙膏的使用者氟斑牙的患病率明显更高。另外，不希望使用正常非处方（OTC）水平的氟化物但仍然希望在具有较少氟化物的产品中获得相同（如果不是更好）的防龋益处的成年人目前没有有效的选择。这仍然是普通人群和科学研究人员中非常敏感的问题，事实上，存在一个完整的同行评审期刊（氟化物），其中包含许多关于氟化物产生的不良影响的出版物。在找到有效的替代办法之前，这种争论和辩论将继续下去。简单地增加口腔输送系统（如牙膏）中的氟化物水平并不是解决问题的办法，特别是如果考虑到氟斑牙的潜在风险。因此，有机会提供防龋益处而不损害牙列的健康。已发表的研究表明，与单一矿物质治疗相比，包括氟化物，钙和磷在内的多种矿物质治疗可以协同作用，提供更高的保护水平。超过95%的美国人口每天刷牙，牙膏是最广泛使用和接受的局部氟化物治疗形式。为了降低潜在的氟斑牙风险而不影响防龋效果，如果配方中可以包含其他与氟化物相容的造牙矿物质，则可以开发一种相对于现有OTC氟化物牙膏含有更低水平氟化物（即~ 500 ppm F）的多矿物质牙膏配方。这种制剂将专门针对儿童和成人，作为一种安全有效的替代品，创造重大价值，并提供重大的公共卫生效益。印第安纳州纳米技术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。基于我们目前对fTCP技术的了解、经验和成功，在本SBIR第I阶段提案中，我们试图确定配制低氟加fTCP牙膏的可行性，该牙膏的防龋功效至少与已确定的OTC含氟牙膏一样好。我们与一家领先的FDA批准和cGMP合规的牙膏制造商和一所知名大学合作，以实现以下特定目标：1）三种牙膏的配方：无氟（安慰剂）;一种含500 ppm氟化物;一种含500 ppm氟化物加fTCP; 2）进行实验室研究，包括一系列FDA推荐的实验室研究，包括氟化物的生物利用度，釉质氟吸收，以及通过REMIN/DEMIN循环逆转白斑病变。3）双盲交叉原位临床研究的临床评价。 公共卫生相关性：临床数据表明，与非处方（OTC）牙膏（约1100 ppm氟化物）相比，使用含氟量较低的牙膏时，龋齿进展会随着时间的推移而增加。但是，不希望使用OTC牙膏但仍然希望至少相同（如果不是更好）的防龋益处来自含氟较少的牙膏的儿童和成人目前没有有效的选择。为了降低潜在的氟斑牙风险而不影响防龋效果，通过将Nanotech创新的氟化物相容的牙齿形成矿物质结合到配方中，可以开发一种相对于现有OTC氟化物牙膏含有更低水平的氟化物（即~ 500 ppm F）的多矿物质牙膏配方。这种制剂将专门针对儿童和成人，作为一种安全有效的替代品，创造重大价值，并提供重大的公共卫生效益。

项目成果

In vitro remineralization of human and bovine white-spot enamel lesions by NaF dentifrices: A pilot study.

• 发表时间: 2011-02
• 期刊: Journal of dentistry and oral hygiene
• 作者: R. Karlinsey;A. C. Mackey;T. J. Walker;K. E. Frederick;D. D. Blanken-D.;S. Flaig;E. R. Walker