Antimicrobial and Regenerative Treatment for Oral Mucositis

口腔粘膜炎的抗菌和再生治疗

基本信息

批准号：
8124755
负责人：
Shenda Baker
金额：
$ 99.28万
依托单位：
SYNEDGEN, INC.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-15 至 2013-03-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8124755
关键词：
Address Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Antibiotics Area Arginine Bacteria Bacterial Infections Biological Assay Cell Line Cell Proliferation Cells Cellulose Cheek structure Chitosan Clinical Clinical Treatment Complex Complication Contracts Data Dehydration Dental Hygiene Dermal Development Dose Drug Formulations EGF gene Excision FDA approved Fatigue Fibroblasts Funding Gingiva Glycerol Goals Growth Factor Guidelines Hamsters Healed Human Immune Immunocompromised Host In Vitro Individual Infection Infection prevention Inflammation Inflammatory Intake Lead Lesion Local Anti-Infective Agents Malnutrition Mammalian Cell Microbial Biofilms Microbiology Modeling Moods Morbidity - disease rate Mucositis Mucous Membrane Natural History Natural regeneration Nutritional Opportunistic Infections Oral Oral cavity Outcome Pain Pathology Peptides Phase Phase II Clinical Trials Pilot Projects Polyethylene Glycols Preparation Prevention Process Property Prophylactic treatment Protocols documentation Radiation Radiation therapy Reactive Oxygen Species Research Resolution Role Safety Saline Salivary Severities Signal Transduction Pathway Small Business Innovation Research Grant Statistical Study Streptococcus mutans Symptoms Systemic infection Testing Time Toxic effect Toxicology Treatment Protocols Water Work Wound Healing antimicrobial arm base chemotherapy commercialization comparative cytokine effective therapy healing high risk improved in vivo keratinocyte killings methicillin resistant Staphylococcus aureus microbial oral biofilm oral care oral infection oral lesion oral mucositis pathogen pre-clinical prevent regenerative research and development research clinical testing resistant strain standard of care wound

项目摘要

DESCRIPTION (provided by applicant): Oral mucositis is a frequent and painful complication of chemotherapy, radiotherapy and immune compromise. Mucositis is associated with significant morbidity including pain, oral lesions, dehydration and nutritional compromise including limiting calorie intake and malnutrition as well as the high risk for systemic infection. In addition, mucositis can lead to systemic toxicities and is associated with symptom complexes that include fatigue, and mood change. The complexity of mucositis pathology is compounded, particularly in the case of myelosuppressed and immunocompromised individuals, by opportunistic pathogens. Current management does not prevent mucosal except in limited indications and do not provide reliable resolution of mucosal lesions. Because of the multi-faceted components contributing to the severity of mucositis, a wide variety of treatment options have been tested including simple oral hygiene, infection prevention, anti- inflammatory agents, reactive oxygen species, salivary function modifiers, coating agents and growth factors. Although these therapies may have efficacy in some cases, a more comprehensive treatment approach is urgently needed. Synedgen is developing an antimicrobial platform based on soluble chitosan derivatives that rapidly clump bacteria, disrupt their biofilms and ultimately kill a wide variety of resistant and non-resistant strains. In addition, the soluble chitosan derivative has demonstrated anti-inflammatory properties and the ability to stimulate wound regeneration. This research aims to provide in vitro data to assess the doses, treatment regimes and formulations that will be effective in prophylaxis and in enhancing resolution of oral mucositis induced by radiation in pre-clinical animal studies. In vitro studies will assess the chitosan derivative's effect on the ability of bacteria to form biofilms and effect on wound healing. Testing in animal models will demonstrate the appropriate dosing and formulation for efficacy in preventing bacterial colonization as well as provide clear evidence of the products ability enhance the natural history of onset to healing in an animal model. Toxicology studies required by the FDA will be contracted to assure compliance with regulatory guidelines. With successful demonstration of efficacy and safety of this oral care product, Phase 2 testing in human trials can be initiated with a goal of rapid commercialization. The successful result of this work will be the optimization of safe and effective formulation, administration protocol and completion of pre-clinical testing required for a highly effective oral therapy that clinical prevents opportunistic infection, and enhances the healing process of oral lesions. PUBLIC HEALTH RELEVANCE: Oral mucositis is a painful, debilitating complication that occurs regularly with chemotherapy, radiation treatment or immuno-suppressants. While many treatments exist to manage the pain and begin to control the outcomes of the lesion development, few treatments are effective. This funding supports an effort to develop an FDA approved daily oral treatment that prevents bacterial infection and complications in mucositis while actively promoting healing and resolution of the oral lesions.

描述（由申请人提供）：口腔粘膜炎是化疗、放疗和免疫损害的常见且痛苦的并发症。粘膜炎与显着的发病率相关，包括疼痛、口腔病变、脱水和营养损害（包括限制热量摄入和营养不良）以及全身感染的高风险。此外，粘膜炎可导致全身毒性，并与疲劳和情绪变化等症状相关。粘膜炎病理学的复杂性因机会性病原体而变得复杂，特别是对于骨髓抑制和免疫功能低下的个体。除有限适应症外，目前的治疗方法不能预防粘膜病变，并且不能可靠地解决粘膜病变。由于导致粘膜炎严重程度的因素是多方面的，因此已经测试了多种治疗方案，包括简单的口腔卫生、感染预防、抗炎剂、活性氧、唾液功能调节剂、涂层剂和生长因子。尽管这些疗法在某些情况下可能有效，但迫切需要更全面的治疗方法。 Synedgen 正在开发一种基于可溶性壳聚糖衍生物的抗菌平台，可快速聚集细菌，破坏其生物膜，并最终杀死多种耐药和非耐药菌株。此外，可溶性壳聚糖衍生物还具有抗炎特性和刺激伤口再生的能力。本研究旨在提供体外数据，以评估在临床前动物研究中有效预防和增强辐射引起的口腔粘膜炎的解决的剂量、治疗方案和配方。体外研究将评估壳聚糖衍生物对细菌形成生物膜的能力的影响以及对伤口愈合的影响。动物模型测试将证明适当的剂量和配方可有效预防细菌定植，并提供明确的证据证明该产品能够增强动物模型中从发病到愈合的自然史。 FDA 要求的毒理学研究将签订合同，以确保符合监管指南。随着该口腔护理产品的功效和安全性得到成功证明，可以启动人体试验的第二阶段测试，以实现快速商业化的目标。这项工作的成功结果将是优化安全有效的配方、给药方案并完成高效口腔治疗所需的临床前测试，从而临床预防机会性感染，并促进口腔病变的愈合过程。公共卫生相关性：口腔粘膜炎是一种令人痛苦、使人衰弱的并发症，在化疗、放疗或免疫抑制剂的治疗中经常发生。虽然有许多治疗方法可以控制疼痛并开始控制病变发展的结果，但很少有治疗方法是有效的。这笔资金支持开发 FDA 批准的日常口腔治疗药物，以预防细菌感染和粘膜炎并发症，同时积极促进口腔病变的愈合和解决。