Trans-tympanic treatment of otitis media

描述(由申请人提供)：中耳炎(OM)是美国最常见的专门治疗的儿童疾病。对一种发病率和复发率如此高的疾病广泛使用全身抗生素，被认为是病原菌耐药性增加的部分原因。局部、持续地将抗菌剂输送到感染部位，可以使局部药物浓度随着时间的推移比全身给药高得多。局部给药还可以最大限度地减少全身暴露，无论是对患者还是对身体其他部位的细菌。更高浓度的抗生素定位于中耳，反过来可以更快、更彻底地根除OM细菌。在这里，我们建议开发一种基于药物输送系统的非侵入性跨鼓室OM治疗方法，该系统将产生足够的抗生素通过鼓膜(TM)以达到有效，并将作为该抗生素的持续释放储存库。我们假设，化学渗透促进剂(CPE)，如在皮肤中常用且安全的，将产生这样的跨鼓膜通量。我们进一步假设，加入氨基酰胺局部麻醉剂(布比卡因)将增强这种流量，并治疗与OM相关的耳痛。我们将开发一种基于水凝胶的系统，该系统将包含CPE和抗生素，并将在较长一段时间内保持在原位。 与公共卫生相关：中耳感染是儿童时期最常见的治疗感染。这项应用的目的是开发一种治疗中耳感染的方法，即在外耳中应用一次凝胶。凝胶中的化学物质将帮助抗生素穿过耳膜；凝胶将其固定在适当的位置。这种方法可以防止抗生素耐药性和毒性。

DESCRIPTION (provided by applicant): Otitis media (OM) is the most common specifically treated childhood disease in the United States. The widespread use of systemic antibiotics against a disease with such high prevalence and recurrence is believed to be partially responsible for the observed increase in resistance among pathogenic bacteria. Local, sustained delivery of antimicrobial agents to the site of infection allows for much higher local drug concentrations over time than could be achieved with systemic administration. Local delivery would also minimize systemic exposure, both to the patient and bacteria elsewhere in the body. Higher concentrations of antibiotics localized to the middle ear, in turn, could allow for a faster and more complete eradication of OM bacteria. Here we propose to develop a noninvasive trans-tympanic OM treatment based on a drug delivery system that will produce a sufficient flux of antibiotic across the tympanic membrane (TM) to be effective, and would also serve as a sustained release reservoir for that antibiotic. We hypothesize that chemical permeation enhancers (CPEs), such as are commonly and safely used in skin, will produce such a trans-tympanic flux. We further hypothesize that inclusion of an animo-amide local anesthetic (bupivacaine) will enhance that flux and treat otic pain associated with OM. We will develop a hydrogel- based system that will contain the CPE and antibiotic, and will maintain it in situ over an extended period. PUBLIC HEALTH RELEVANCE: Middle ear infections are the most commonly treated infections in childhood. The purpose of this application is to develop a means of treating middle ear infections by applying a gel in the outer ear, once. Chemicals in the gel will help antibiotics cross the eardrum; the gel holds it in place. This approach could prevent antibiotic resistance and toxicity.