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: 8312757
• 负责人: CRAIG S MILLER
• 金额: $ 31.7万
• 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 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8312757
• 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. PUBLIC HEALTH RELEVANCE: This project presents the unique collaboration between the agriculture industry, oral biologists, small business, and a large healthcare company that 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. Use of this novel adjunctive oral hygiene aid could greatly reduce the cost of dental care by preventing oral disease before it occurs, and can be used by those who lack access to conventional oral hygiene measures.

描述（由申请人提供）：牙周炎是一种多微生物疾病，其中在龈下沟中的生物膜中成熟的复杂微生物生态引发慢性免疫炎症病变，破坏牙周组织的软组织和硬组织。尽管近年来口腔健康有了很大的改善，但牙龈炎和牙周病仍然很突出，并影响美国30岁以上的所有成年人中的大约一半，在得不到充分服务的发展中国家和不发达国家，这种现象甚至更为普遍。鉴定治疗剂以能够更有效地控制和/或预防牙龈炎症的能力是目前改善人群口腔健康的商业策略的关键方面。为了满足对安全、具有成本效益的抗牙龈炎产品/技术的未满足的需求，该产品/技术可促进患者的高依从性并可纳入日常使用中，我们开发了一种新型的直接压缩口香糖制剂，其含有具有抗炎、抗菌和抗病毒作用的冻干黑莓粉（FBP）。我们的初步研究结果表明，这种口香糖产品在商业上是可行的，并可能有效地预防和/或治疗牙龈炎。该第II阶段STTR提案的目标是制造含有FBP的口香糖，该口香糖将生物活性植物化学物质递送到口腔，并测试其在预防人类生物膜形成和牙龈炎方面的功效。研究将 确定最终口香糖产品规格和制造方法。将生产cGMP批次，并进行质量控制检测和质量保证放行。初始临床研究的新药临床试验申请（IND）的提交和批准将根据我们与FDA的IND前会议的指导进行。在一项随机、双盲、单中心临床功效研究中，我们将评估口香糖降低i）使用可取回的牙釉质芯片模型在牙釉质上和唾液中的几种牙斑形成细菌物种的水平，和ii）人类临床牙龈炎症、口腔微生物负荷和炎症的唾液生物标志物的能力。这些研究如果成功，将导致随后的IND提交，以完成多中心试验，并最终将该产品作为“植物性药品”注册的NDA提交，如FDA指南文件所述。Four Tigers LLC与美国东部最大的黑莓农场WindStone Farms合作，开发和商业化黑莓衍生的健康和医疗产品。研究人员组建了一个高度跨学科的团队，包括农业，口腔生物学家，小企业和缅因州的汤姆公司，一家专注于全天然产品的大型医疗保健公司，这将共同导致一种创新的黑莓口香糖的制造和商业可用性，该口香糖从冻干果粉中释放和递送天然生物活性物质，这将有助于预防/治疗牙龈炎。 公共卫生相关性：该项目展示了农业，口腔生物学家，小企业和大型医疗保健公司之间的独特合作，这将导致一种创新的黑莓口香糖的制造和商业可用性，该口香糖从冻干果粉中释放和提供天然生物活性物质，有助于预防/治疗牙龈炎。使用这种新型的预防性口腔卫生辅助剂可以通过在口腔疾病发生之前预防口腔疾病来大大降低牙齿护理的成本，并且可以由那些无法获得常规口腔卫生措施的人使用。