Antimicrobial and Regenerative Treatment for Oral Mucositis

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和痛苦的并发症。粘膜炎与显著的发病率相关，包括疼痛、口腔病变、脱水和营养不良，包括限制卡路里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，并与包括疲劳和情绪变化的症状复合体相关。粘膜炎病理学的复杂性由于机会性病原体而变得复杂，特别是在骨髓抑制和免疫功能低下的个体的情况下。目前的管理不能防止粘膜，除非在有限的适应症，并没有提供可靠的解决粘膜病变。由于导致粘膜炎严重性的多方面成分，已经测试了各种各样的治疗选择，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、包衣剂和生长因子。虽然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，这种衍生物可以快速聚集细菌，破坏它们的生物膜，并最终杀死各种耐药和非耐药菌株。此外，可溶性壳聚糖衍生物已被证明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，以评估剂量，治疗方案和制剂，将有效地预防和提高在临床前动物研究中辐射诱导的口腔粘膜炎的解决。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。在动物模型中进行的试验将证明适当的剂量和制剂在预防细菌定植方面的有效性，并提供明确的证据证明产品能够增强动物模型中发病至愈合的自然史。将签订FDA要求的毒理学研究合同，以确保符合监管指南。随着这种口腔护理产品的有效性和安全性的成功证明，可以启动人体试验的第二阶段测试，目标是快速商业化。这项工作的成功结果将是优化安全有效的制剂、给药方案和完成高效口服治疗所需的临床前试验，该治疗可在临床上预防机会性感染，并增强口腔病变的愈合过程。 公共卫生相关性：口腔粘膜炎是一种痛苦的，使人衰弱的并发症，经常发生与化疗，放射治疗或免疫抑制剂。虽然存在许多治疗方法来控制疼痛并开始控制病变发展的结果，但有效的治疗方法很少。这笔资金支持开发FDA批准的日常口腔治疗，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。

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.