Antimicrobial and Regenerative Treatment for Oral Mucositis

描述（申请人提供）：口腔黏膜炎是化疗、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，以及全身性感染的高风险。此外，粘膜炎可导致全身毒性，并伴有疲劳和情绪变化等症状。粘膜炎病理的复杂性是复杂的，特别是在骨髓抑制和免疫功能低下的个体的情况下，由机会性病原体。目前的治疗不能预防粘膜病变，除非在有限的适应症，不能提供可靠的解决粘膜病变。由于造成黏膜炎严重程度的多方面因素，各种各样的治疗方案已经被测试，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，但迫切需要一种更全面的治疗方法。Synedgen正在开发一种基于可溶性壳聚糖衍生物的抗菌平台，该平台可以快速聚集细菌，破坏其生物膜，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具有抗炎特性和促进伤口再生的能力。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放射引起的口腔黏膜炎的剂量、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能力的影响以及对伤口愈合的影响。在动物模型中进行的测试将证明适当的剂量和配方在防止细菌定植方面的功效，并提供明确的证据，证明产品能够增强动物模型中发病到愈合的自然史。FDA要求的毒理学研究将签订合同，以确保遵守监管准则。在成功证明该口腔护理产品的有效性和安全性后，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配方，给药方案和完成临床前试验所需的高效口服疗法，临床预防机会性感染，促进口腔病变的愈合过程。

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.