Unique Anti-microbial Rinse to Reduce Oral Inflammation

描述（由申请人提供）：牙周病最近被确定为系统性疾病（如胰腺癌、心血管疾病（动脉粥样硬化、心肌梗死和中风）和糖尿病）以及妊娠并发症（如早产）发病率和死亡率增加的危险因素。牙周病是由牙菌斑生物膜中的微生物引起的。口腔细菌及其成分引发的炎症反应与牙周组织破坏的局部发病机制有关，并可能导致全身性疾病的发展。虽然因果关系尚未得到证实，但一些研究表明，口腔健康干预可能会影响炎症和疾病的生物标志物。该项目的目标是开发一种处方抗菌口腔漱口水，以减少口腔内的细菌生物负荷，并对抗口腔疾病和炎症。目前的口腔冲洗产品要么充满了诸如染色和味道改变等副作用，限制了它们在急性环境中的使用，要么是无效的。根据初步研究，本文开发的口腔冲洗液预计比目前可用的处方产品更有效，而且没有副作用。高效口腔漱口水的开发可能会对公众健康产生深远的影响，并取得重大的商业成功。该研究是一个快速通道提案，将I期和II期研究结合在一个申请中。第一阶段部分有两个具体目标：用于临床试验的复方口腔冲洗制剂评估口腔冲洗液在牙龈炎症的人体临床试验中的剂量反应，并研究对指示全身性疾病的生物标志物的影响。第二阶段有三个具体目标：用于临床试验的复方口腔冲洗制剂在牙龈炎的人类临床试验中评估口腔冲洗液，以满足FDA的要求，并研究其对指示全身性疾病的生物标志物的影响。

DESCRIPTION (provided by applicant): Periodontal disease has been recently identified as a risk factor for increased morbidity and mortality for systemic diseases such as pancreatic cancer, cardiovascular disease (atherosclerosis, myocardial infarction, and stroke), and diabetes, as well as for pregnancy complications such as preterm birth. It is well established that periodontal disease results from microorganisms in dental plaque biofilm. Inflammatory reactions initiated by oral bacteria and their components are implicated locally in the pathogenesis of periodontal tissue destruction, and may contribute to the development of systemic disease. While causality has yet to be confirmed, some studies have shown that oral health interventions may impact biological markers of inflammation and disease. The goal of this project is to develop a prescription antimicrobial oral rinse to reduce bacterial bioburden in the oral cavity and combat oral disease and inflammation. Current oral rinse products are either fraught with side effects such as staining and taste alterations that limit their usage to acute settings, or are ineffective. Based on preliminary studies, the oral rinse developed herein is expected to be more effective than currently available prescription products without the side effects. The development of a highly effective oral rinse may have the potential to have a profound impact on public health and achieve significant commercial success. This study is a Fast-Track proposal that combines both Phase I and Phase II studies in one application. The Phase I portion has two Specific Aims: Aim 1. Compound Oral Rinse Formulations for Use in Clinical Trials Aim 2. Evaluate Dose-Response of the Oral Rinse in a Human Clinical Trial of Gingival Inflammation and Investigate Effects on Biological Markers Indicative of Systemic Disease. The Phase II portion has three Specific Aims: Aim 1. Compound Oral Rinse Formulations for Use in Clinical Trials Aim 2. Evaluate the Oral Rinse in a Human Clinical Trial of Gingivitis to Satisfy FDA Requirements and Investigate Effects on Biological Markers Indicative of Systemic Disease.