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: 8538937
• 负责人: CRAIG S MILLER
• 金额: $ 31.36万
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8538937
• 关键词: Address; Adult; Affect; Age; Agriculture; Anthocyanins; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antiviral Agents; Bacteria; Berry; Biological Assay; Biological Factors; Biological Markers; Botanicals; Businesses; Cardiovascular system; Characteristics; Chewing Gum; Chronic; Clinical; Clinical Research; Clinical Trials; Collaborations; Complex; Country; Data; Dental Care; Dental Enamel; Dental Hygiene; Dental Plaque; Development; Diabetes Mellitus; Disease; Double-Blind Method; Drug Delivery Systems; Drug Formulations; Ecology; Event; Exhibits; Farming environment; Freeze Drying; Fruit; Fusobacterium nucleatum; Genetic; Gingiva; Gingivitis; Goals; Health; Healthcare; High Prevalence; Human; Immune; Immune response; Immunology; In Vitro; Incidence; Industry; Infection; Inflammation; Inflammation Mediators; Inflammatory; Investigational New Drug Application; Lead; Lesion; Low Birth Weight Infant; Maine; Mastication; Measures; Medical; Methods; Microbial Biofilms; Military Personnel; Modeling; Mouth Diseases; Oral; Oral Medicine; Oral cavity; Oral health; Pattern; Periodontal Diseases; Periodontic specialty; Periodontitis; Periodontium; Pharmaceutical Preparations; Pharmacy (field); Phase; Phytochemical; Population; Porphyromonas gingivalis; Powder dose form; Predisposition; Prevention; Property; Protocols documentation; Quality Control; Randomized; Reactive Oxygen Species; Reporting; Research; Research Personnel; Resources; Risk; Risk Marker; Saliva; Severities; Simulate; Small Business Technology Transfer Research; Streptococcus mutans; Systemic disease; Technology; Testing; Therapeutic; Tigers; Tissues; Tooth Loss; Translational Research; Underserved Population; United States; antimicrobial; bactericide; base; clinical efficacy; commercialization; compliance behavior; cost; cost effective; improved; innovation; meetings; microbial; novel; polyphenol; prevent; quality assurance

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 immune-inflammatory lesion that destroys soft and hard tissues of the periodontium. Despite the great improvement in oral health in recent years, gingivitis and periodontal disease remain prominent and affect about half of all adults above the age of 30 years in the U.S., with an even higher prevalence in the underserved and developing and undeveloped countries. 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. To address the unmet need for safe, cost-effective anti-gingivitis product/technology that promotes high patient compliance and could be incorporated into daily use, we have developed a novel, direct compression chewing gum formulation that contains freeze-dried blackberry powder (FBP) which is anti-inflammatory, antibacterial and antiviral. Our preliminary findings suggested this gum product is commercially viable and potentially effective for the prevention and/or treatment of gingivitis. The goal of this Phase II STTR proposal is to manufacture the chewing gum containing FBP that delivers bioactive phytochemicals to the oral cavity and test its efficacy in preventing biofilm formation and gingivitis in humans. Studies will determine the final gum product specifications and manufacturing method. A cGMP batch will be manufactured and Quality Control testing and Quality Assurance release will be performed. Submission and approval of an Investigational New Drug Application (IND) for an initial clinical study will be pursued based on guidance from our pre-IND meeting with FDA. In a randomized, double-blind, single center clinical efficacy study, we will assess the chewing gum's ability to reduce i) levels of several plaque-forming bacteria species on enamel and in saliva using the retrievable enamel chip model, and ii) clinical gingival inflammation, oral microbial burden and saliva biomarkers of inflammation in humans. These studies, if successful, will lead to a subsequent IND submission to complete multi-center trials and eventual NDA submission of the product for registration as a "Botanical Drug Product" as addressed under the FDA Guidance Document of the same title. Four Tigers 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 encompassing collaborations between the agriculture industry, oral biologists, small business, and Tom's of Maine, a large healthcare company that focuses on all-natural products, that together will lead to the manufacture and commercial availability of an innovative blackberry chewing gum that releases and delivers natural bioactive substances from freeze-dried fruit powder that will help prevent/treat gingivitis.

描述（由申请人提供）：牙周炎代表一种多细胞性疾病，其中一种复杂的微生物生态学，可在亚gingival沟中生物膜成熟，触发慢性免疫炎症病变，破坏了牙周组织的软组织。尽管近年来口腔健康状况有了很大的改善，但在美国30岁以上的所有成年人中，牙龈炎和牙周疾病仍然很明显，在服务不足，发展不足和发展的国家中的患病率更高。鉴定治疗剂的能力，使得更有效的控制和/或预防牙龈发炎，是当前改善人口口腔健康的商业策略的关键方面。为了满足对促进患者依从性高的安全性，具有成本效益的抗生生炎产品/技术的未满足需求，并可以纳入日常使用中，我们开发了一种新型的，直接的压缩咀嚼口香糖配方，其中包含冻干黑莓粉（FBP），该配方（FBP）是抗炎，抗菌和抗病毒和抗病毒。我们的初步发现表明，这种口香糖产品在商业上是可行的，并且可能对预防和/或治疗牙龈炎有效。该II期STTR提案的目的是生产含有FBP的口香糖，该牙龈为口腔提供生物活性植物化学物质，并测试其在人类中防止生物膜形成和牙龈炎方面的功效。研究将 确定最终的口香糖产品规格和制造方法。将制造CGMP批次，并将执行质量控制测试和质量保证释放。根据我们与FDA的预先会议的指导，将对初步临床研究的研究新药应用（IND）提交和批准。在一项随机，双盲，单一中心临床功效研究中，我们将使用可检索的搪瓷芯片模型以及II）临床牙龈炎症，口腔微生物责任和萨利瓦生物症的临床牙齿炎症，使用可检索的牙釉质芯片模型来评估牙龈降低牙龈降低几种形成斑块的细菌物种的能力。这些研究，如果成功的话，将导致随后的IND提交，以完成多中心试验，并最终提交该产品以注册为“植物药物产品”，如同一标题的FDA指南文件所述。四个Tigers LLC与美国东部最大的黑莓农场Windstone Farms合作开发和商业化了来自黑莓的健康和医疗产品。调查人员组建了一支高度跨学科的团队，包括农业行业，口腔生物学家，小型企业和缅因州的汤姆（Tom of Maine）之间的合作，这是一家大型医疗保健公司，重点关注全天然产品，这些公司将导致制造和商业用途，以防止创新的黑莓咀嚼量，从而使自然味道供应冻结，从而使自然粉末散发出来的果实，以否定果实的果实，以弥补自然效果的效果，以否决粉末范围的药物，以否决粉末范围。牙龈炎。