Development of a Dissolving Film for Allergen Immunotherapy in Children

描述(申请人提供)：过敏性疾病是儿童时期最常见的慢性疾病，导致严重的发病率。然而，过敏原特异性注射免疫疗法对许多儿童来说是不可接受的，而且对某些类型的过敏可能风险太高，仍然是唯一被批准的过敏性疾病的疾病修饰疗法。舌下免疫疗法已被证明对食物过敏和空气过敏的治疗都更安全，但目前的方法没有在有效性、安全性或实用性方面进行优化，也没有被批准在美国使用。粘附性溶解薄膜改进了目前的液体免疫治疗方法，因为它(1)延长了抗原提呈细胞和过敏原之间的接触，这对免疫治疗的疗效至关重要，(2)允许更灵活的剂量，标准剂量比目前可用的更高和更低，(3)是一种更实用的儿童使用方法，几乎不需要合作，(4)与液体不同，它是 不受渴望的风险的影响。我们已经开发了一种用于治疗花生过敏的薄膜。在这笔赠款中，我们建议将这种方法扩展到儿童的其他重要过敏原，并探索优化其在儿童中的使用的方法。目的1是开发和改进治疗蟑螂和猫过敏的口腔溶解纸条。这些过敏症是导致儿童过敏性鼻炎和哮喘的两个最重要的因素，每一种都给电影设计带来了独特的挑战和机会。目标2是通过评估口腔中不同的放置位置以及如果需要的话，配方对过敏原在口腔中的持久性和适口性的影响，来优化溶解薄膜的药代动力学和适口性。这里开发的这些方法有可能解决目前限制或完全阻止儿童免疫疗法从研究环境转化到临床的根本问题。

DESCRIPTION (provided by applicant): Allergic diseases constitute the most common chronic diseases of childhood and cause significant morbidity. However, allergen-specific injection immunotherapy, which is not acceptable to many children and may be too risky for some types of allergy, remains the only approved disease modifying treatment for allergic diseases. Sublingual immunotherapy has been shown to be safer for treatment of both food and aeroallergies, but current methods are not optimized for efficacy, safety or practicality, and are not approved for use in the U.S.. A mucoadhesive, dissolving film improves upon current liquid methods of immunotherapy because it (1) prolongs contact between antigen presenting cells and allergen, which is vital for the efficacy of immunotherapy, (2) allows for more flexible dosing, with both higher and lower standardized doses than are currently available, (3) is a more practical method for use in children, requiring little cooperation and, (4) unlike liquids, is not subject to the risk of aspiration. We have developed such a film for use in the treatment of peanut allergy. In this grant, we propose to extend this method to other important allergens for children and explore methods to optimize its use in children. Aim 1 is to develop and refine orally dissolving strips for treatment of cockroach and cat allergies. These allergies are two of the most important contributors to allergic rhinitis and asthma in children, and each present unique challenges and opportunities for design of a film. Aim 2 is to optimize the pharmacokinetics and palatability of a dissolving film by evaluating the effect of different placements in the mouth and, if need be, formulations on persistence of allergen in the mouth and on palatability. This methods developed here have to the potential to address the fundamental problems that currently limit or entirely prevent translation of immunotherapy in children from research settings to the clinic.