Delivery of Polyphenols in Gum for Treatment of Gingivitis

在牙龈中输送多酚以治疗牙龈炎

• 批准号: 7664694
• 负责人: CRAIG S MILLER
• 金额: $ 10.07万
• 依托单位: FOUR TIGERS, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-23 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7664694
• 关键词: Address; Affect; Anogenital venereal warts; Anthocyanins; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Biological; Botanicals; Businesses; Cardiovascular system; Characteristics; Chemistry; Chewing Gum; Chronic; Clinical; Complex; Data; Dental caries; Development; Devices; Diabetes Mellitus; Disease; Drug Delivery Systems; Drug Formulations; Ecology; Epigallocatechin Gallate; Epithelial Cells; Event; Farming environment; Genetic; Gingiva; Gingivitis; Goals; Health; Herpesviridae; Human; Immune response; Immunology; Incidence; Infection; Inflammation; Inflammation Mediators; Inflammatory; Lead; Left; Lesion; Licensing; Low Birth Weight Infant; Malignant Neoplasms; Mastication; Measures; Mechanics; Medical; Methods; Microbial Biofilms; Mouth Diseases; Oral; Oral Medicine; Oral cavity; Oral health; Outcome; Patients; Periodontal Diseases; Periodontic specialty; Periodontitis; Periodontium; Pharmaceutical Preparations; Pharmacology; Pharmacy (field); Phase; Phenols; Phytochemical; Population; Predisposition; Prevalence; Prevention; Property; Qualifying; Reactive Oxygen Species; Research; Research Personnel; Risk; Risk Marker; Severities; System; Systemic disease; Testing; Therapeutic; Tigers; Tissues; Tooth Loss; Translational Research; Translations; United States; Viral; Water; analytical method; antimicrobial; cost; experience; improved; innovation; macrophage; microbial; novel; oral care; oral mucositis; pathogen; polyphenol; prevent; prototype; public health relevance

DESCRIPTION (provided by applicant): Periodontitis represents a polymicrobial disease, in which a complex microbial ecology that matures in biofilms in the subgingival sulcus triggers a chronic immunoinflammatory lesion that destroys soft and hard tissues of the periodontium. The ability to identify therapeutics, to enable more effective control and/or prevention of gingival inflammation, is a critical facet of current commercial strategies to improve oral health of the population. The goal of this Phase I proposal is to further develop a novel chewing gum containing blackberry extract that delivers bioactive phytochemicals to the oral cavity and test its efficacy in preventing gingivitis. The bioactive phytochemicals in the extract are polyphenols with the most notable being anthocyanins. Methods to prepare and stabilize the extract have already been developed, as well as a prototype two gram blackberry extract chewing gum. In addition, the extract has already been found to have anti-oxidant, anti-cancer, anti- inflammatory, anti-bacterial, and anti-viral properties. In this 12 month research plan, four Specific Aims are proposed as follows: Aim 1: Refine the development of chewing gum as a delivery strategy for blackberry extract as a potent, natural anti-gingivitis agent. To achieve this Aim, the Investigators will, i) complete development of qualified stability-indicating analytical method for anthocyanins and phenols in the blackberry extract and the gum prototype, ii) develop methods to extract anthocyanins and phenols from the gum, iii) determine the release rate of anthocyanins and phenols using a mechanical chewing device, iv) perform an accelerated 1 month stability study and establish preliminary release specifications for the clinical batches. Aim 2: Test the hypothesis that bioactive phytochemicals in blackberry extract inhibit mechanisms associated with gingivitis. To achieve this Aim, the Investigators will, i) evaluate the anti-inflammatory properties of the blackberry extract in human oral epithelial cells and macrophages, and ii) test the antimicrobial properties of the blackberry extract against periodontal pathogens and human herpes viruses. Four Tigers LLC, and its wholly-owned subsidiary Berryceuticals LLC, has partnered with WindStone Farms, the largest blackberry farm in the eastern part of the United States, to develop and commercialize health and medical products derived from blackberries. The investigators have assembled a highly interdisciplinary team of investigators encompassing expertise in pharmaceutics, novel drug delivery systems for the oral cavity, periodontics, immunology, and oral medicine. The chewing gum is an existing drug delivery approach that represents a practical and potentially highly versatile strategy to improve patient oral care. Specifically, the gum formulation allows for the localized release of stabilized and highly potent anti-oxidant and anti- inflammatory phytochemicals within the oral cavity. The expected outcome may be improved treatments of gingivitis and periodontal disease as well as caries, oral mucositis, and other disorders and diseases of the oral cavity. PUBLIC HEALTH RELEVANCE: The ability to identify therapeutics, to enable more effective control and/or prevention of gingival inflammation, is a critical facet of current commercial strategies to improve oral health of the population. The goal of this Phase I proposal is to further develop a novel chewing gum delivery system containing blackberry extract that delivers bioactive natural compounds to the oral cavity and test its efficacy in preventing gingivitis. The bioactive compounds in the blackberry extract are polyphenols with the most notable being anthocyanins. These polyphenols have been shown to have very significant anti-inflammatory and anti-microbial properties, among other biological activities. The expected outcome may be improved treatments of gingivitis and periodontal disease as well as caries, oral mucositis, and other disorders and diseases of the oral cavity. This product is being developed as one of the first "Botanical Drug Products" as defined by the FDA in their 2004 Guidance Document.

描述(申请人提供)：牙周炎是一种多菌类疾病，复杂的微生物生态在牙龈下沟的生物膜中成熟，引发慢性免疫炎症损害，破坏牙周组织的软组织和硬组织。确定治疗方法的能力，以便能够更有效地控制和/或预防牙周炎，是当前改善人口口腔健康的商业战略的关键方面。这项第一阶段提案的目标是进一步开发一种含有黑莓提取物的新型口香糖，该口香糖可以将生物活性植物化学物质输送到口腔，并测试其预防牙周炎的效果。提取物中的生物活性植物化学物质是多酚，其中最引人注目的是花青素。制备和稳定提取物的方法已经开发出来，以及两克黑莓提取物口香糖的原型。此外，该提取物已被发现具有抗氧化、抗癌、抗炎、抗菌和抗病毒等特性。在这一12个月的研究计划中，提出了四个具体目标如下：目标1：完善口香糖的开发，将其作为黑莓提取物作为一种有效的、天然的抗牙周炎药物的输送策略。为了实现这一目标，研究人员将：i)完成对黑莓提取物和树胶原型中花色苷和酚的合格稳定性指示分析方法的开发；ii)开发从树胶中提取花色苷和酚的方法；iii)使用机械咀嚼设备测定花青素和酚的释放速率；iv)进行加速的1个月稳定性研究，并建立临床批次的初步释放规格。目的2：验证黑莓提取物中具有生物活性的植物化学物质抑制牙周炎机制的假说。为了实现这一目标，研究人员将：i)评估黑莓提取物对人类口腔上皮细胞和巨噬细胞的抗炎特性；ii)测试黑莓提取物对牙周病原体和人类疱疹病毒的抗菌特性。Four Tigers LLC及其全资子公司Berryceuticals LLC已与美国东部最大的黑莓农场WindStone Farm合作，开发黑莓保健和医疗产品并将其商业化。研究人员组建了一支高度跨学科的调查团队，其中包括制药学、口腔新型给药系统、牙周学、免疫学和口腔医学方面的专业知识。口香糖是一种现有的药物输送方法，它代表了一种实用的、潜在的高度通用的策略，以改善患者的口腔护理。具体地说，这种口香糖配方允许在口腔内局部释放稳定和高效的抗氧化和抗炎植物化学物质。预期的结果可能是牙周炎和牙周病以及龋齿、口腔粘膜炎和其他口腔疾病和疾病的改善治疗。 公共卫生相关性：确定治疗方法的能力，以便能够更有效地控制和/或预防牙周炎，是当前改善人口口腔健康的商业战略的关键方面。这项第一阶段提案的目标是进一步开发一种含有黑莓提取物的新型口香糖递送系统，该系统可以将具有生物活性的天然化合物递送到口腔，并测试其预防牙龈炎的效果。黑莓提取物中的生物活性化合物是多酚，其中最引人注目的是花青素。这些多酚已被证明具有非常显著的抗炎和抗微生物特性，以及其他生物活性。预期的结果可能是牙周炎和牙周病以及龋齿、口腔粘膜炎和其他口腔疾病和疾病的改善治疗。该产品被开发为FDA在2004年指南文件中定义的首批“植物药产品”之一。