Laboratory and clinical evaluation of prospective fluoride rinses containing TCP-

含有 TCP-的前瞻性氟化物冲洗液的实验室和临床评估

• 批准号: 7798356
• 负责人: ROBERT L KARLINSEY
• 金额: $ 26.51万
• 依托单位: INDIANA NANOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7798356
• 关键词: 5 year old; Address; Affect; Age; American; Bioavailable; Biological Availability; Calcium; Calcium Fluoride; Centers for Disease Control and Prevention (U.S.); Characteristics; Child; Clinical; Clinical Research; Dental; Dental Enamel; Dental Schools; Dental caries; Dentists; Development; Disease; Double-Blind Method; Drug Formulations; Evaluation; Fluorides; Genetic Crossing Over; Goals; Health Benefit; Health Sciences; Hybrids; In Situ; In Vitro; Incidence; Indiana; Laboratories; Laboratory Study; Legal patent; Lesion; Life; Manufactured Supplies; Manufacturer Name; Marketing; Minerals; Nanotechnology; National Institute of Dental and Craniofacial Research; Oral; Oral health; Orthodontic Brackets; Orthodontic Retainers; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phosphorous; Placebo Control; Population; Preschool Child; Procedures; Prosthesis; Public Health; Publishing; Relative (related person); Research; Research Proposals; Science; Small Business Innovation Research Grant; Sodium Dodecyl Sulfate; Staging; Technology; Texas; Therapeutic; Time; Tissues; Toothpaste; Universities; White Spots; Xerostomia; anticaries; base; calcium phosphate; cancer therapy; commercialization; disorder prevention; experience; federal poverty level; high risk; improved; innovation; nanoscale; permanent tooth; prospective; prototype; remin-demin; remineralization; research clinical testing; research facility; restorative dentistry; solid state; statistics; success; technology development; tricalcium phosphate; uptake

DESCRIPTION (provided by applicant): Recently, the Centers for Disease Control and Prevention publicized findings from the largest US study performed on dental health in 25 years indicating that while oral health is improving for most Americans, tooth decay among preschool children (between the ages of 2 and 5 years old) increased from 24% (between 1988-1994) to 28% (between 1999-2004). Of the types of oral formulations, mouthrinses are especially appealin not only because of simplicity and convenience but also for high-risk caries groups including those with orthodontic brackets and retainers, prostheses and restorations, dental erosion, children with developing permanent dentition, and those experiencing hyposalivation caused by medications and/or cancer treatments. 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. However, a major problem facing multi-mineral formulations, however, is that bioavailable fluoride and calcium cannot coexist in a single stable formulation for long periods of time, which ultimately reduces the shelf-life and therapeutic performance of the multi-mineral formulation. Because of the sensitivity of fluoride, currently there is no single-compartment multi-mineral mouthrinse available commercially in the US. Indiana Nanotech has patent- pending technology that functionalizes 2-tricalcium phosphate (TCP) with sodium lauryl sulfate (SLS) to create TCP-SLS hybrid materials that are compatible with fluoride. Importantly, when combined in an established and commercially available OTC fluoride mouthrinse formulation, TCP-SLS boosted enamel fluoride uptake (~ 25%) and strengthened enamel 'white-spots' (~ 50%) relative to the commercial OTC fluoride mouthrinse. The long-term goal of this research is to commercialize an economical OTC multi-mineral mouthrinse formulation that provides increased dental health benefits than would otherwise be observed with fluoride alone. As part of our development and commercialization activities, we have developed this Phase II research proposal to the NIDCR that addresses the following Specific Aims: 1) Evaluation of stability and in vitro efficacy of NaF mouthrinse formulations containing TCP-SLS. These activities include FDA- recommended laboratory studies, including fluoride bioavailability, enamel fluoride uptake, and white-spot lesion reversal via remin/demin cycling; 2) understand the remineralization effect of TCP-SLS. This will include extending our current understanding of TCP-SLS by probing the bonding and interface characteristics of TCP-SLS, as well the enamel tissue that is treated with TCP-SLS and fluoride; and 3) Evaluation of the most promising prototype mouthrinse formulation against a commercially available fluoride mouthrinse rinse in a placebo-controlled double-blind cross-over in situ clinical study. PUBLIC HEALTH RELEVANCE: Recently, the Centers for Disease Control and Prevention publicized findings from the largest US study performed on dental health in 25 years indicating that while oral health is improving for most Americans, tooth decay among preschool children (between the ages of 2 and 5 years old) increased from 24% (between 1988-1994) to 28% (between 1999-2004). Of the types of oral formulations, mouthrinses are especially appealing not only because of simplicity and convenience but also for high-risk caries groups including those with orthodontic brackets and retainers, prostheses and restorations, dental erosion, children with developing permanent dentition, and those experiencing hyposalivation caused by medications and/or cancer treatments. However, a major problem facing multi-mineral formulations, however, is that bioavailable fluoride and calcium cannot coexist in a single stable formulation for long periods of time, which ultimately reduces the shelf-life and therapeutic performance of the multi-mineral formulation. Therefore, developing a daily-use mouthrinse formulation comprising calcium minerals that function synergistically with fluoride to provide greater anticaries performance relative fluoride alone may provide a significant public health benefit.

描述（申请人提供）：最近，疾病控制和预防中心公布了25年来美国最大的牙齿健康研究结果，表明虽然大多数美国人的口腔健康正在改善，学龄前儿童（2至5岁）的蛀牙率从24%（1988-1994年）上升到28%（1999-2004年）。在各种口服制剂中，漱口水特别有吸引力。 这不仅是因为简单和方便，而且也适用于高危龋齿群体，包括那些具有正畸托槽和保持器、修复体和矫正体、牙齿侵蚀、恒牙列发育的儿童以及那些经历由药物和/或癌症治疗引起的唾液分泌不足的人。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。然而，多矿物质制剂面临的主要问题是，生物可利用的氟化物和钙不能长时间共存于单一稳定制剂中，这最终降低了多矿物质制剂的保质期和治疗性能。由于氟化物的敏感性，目前在美国没有商业上可获得的单隔室多矿物漱口水。印第安纳州纳米技术公司拥有一项正在申请专利的技术，该技术利用十二烷基硫酸钠（SLS）对2-磷酸三钙（TCP）进行官能化，以创造出与氟化物相容的TCP-SLS混合材料。重要的是，当与一种已建立的市售OTC氟化物漱口水配方组合时，相对于市售OTC氟化物漱口水，TCP-SLS可促进牙釉质氟化物吸收（约25%）并强化牙釉质“白斑”（约50%）。这项研究的长期目标是将一种经济的OTC多矿物质漱口液配方商业化，该配方比单独使用氟化物时提供更多的牙齿健康益处。作为我们开发和商业化活动的一部分，我们已经向NIDCR提出了这一II期研究提案，该提案涉及以下具体目标：1）评价含TCP-SLS的NaF漱口液制剂的稳定性和体外功效。这些活动包括FDA推荐的实验室研究，包括氟化物生物利用度、牙釉质氟化物吸收和通过remin/demin循环逆转白斑病变; 2）了解TCP-SLS的矿化作用。这将包括通过探测TCP-SLS的结合和界面特征以及用TCP-SLS和氟化物处理的釉质组织来扩展我们目前对TCP-SLS的理解;以及3）在安慰剂对照的双盲交叉原位临床研究中，评价最有前途的原型漱口水配方与市售含氟漱口水。 公共卫生关系：最近，疾病控制和预防中心公布了25年来美国最大的牙齿健康研究结果，表明虽然大多数美国人的口腔健康正在改善，但学龄前儿童（2至5岁）的蛀牙率从24%（1988-1994年）增加到28%（1999-2004年）。在口服制剂的类型中，漱口水特别有吸引力，这不仅是因为其简单和方便，而且对于高风险龋齿群体也是如此，所述高风险龋齿群体包括具有正畸托槽和固位器、假体和修复体、牙齿侵蚀、具有正在发育的恒牙列的儿童以及经历由药物和/或癌症治疗引起的唾液分泌不足的那些。 然而，多矿物质制剂面临的主要问题是，生物可利用的氟化物和钙不能长时间共存于单一稳定制剂中，这最终降低了多矿物质制剂的保质期和治疗性能。因此，开发包含钙矿物质的日常使用的漱口液制剂可以提供显著的公共健康益处，所述钙矿物质与氟化物协同作用以提供相对于单独的氟化物更大的防龋性能。