Development of a Dissolving Film for Allergen Immunotherapy in Children

描述（由申请人提供）：过敏性疾病是儿童最常见的慢性疾病，并导致显著的发病率。 然而，过敏原特异性注射免疫疗法，这是不能接受的许多儿童，可能是太危险的某些类型的过敏，仍然是唯一批准的疾病修饰治疗过敏性疾病。 舌下免疫疗法已被证明对食物和空气过敏的治疗更安全，但目前的方法在疗效、安全性或实用性方面尚未优化，并且未被批准在美国使用。 一种粘膜粘附溶解膜改进了目前的液体免疫治疗方法，因为它（1）抑制抗原呈递细胞和过敏原之间的接触，这对免疫治疗的功效至关重要，（2）允许更灵活的剂量，具有比目前可用的更高和更低的标准化剂量，（3）是用于儿童的更实用的方法，需要很少的合作，（4）与液体不同， 不会有吸入的危险。 我们已经开发了这样一种用于治疗花生过敏的薄膜。 在这项资助中，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使用的方法。 目的1是开发和改进用于治疗蟑螂和猫过敏的口腔溶解条。 这些过敏是儿童过敏性鼻炎和哮喘的两个最重要的贡献者，每一个都为电影设计带来了独特的挑战和机会。 目的2是通过评价口腔中不同放置位置以及（如果需要）制剂对口腔中过敏原持久性和适口性的影响，优化溶解膜的药代动力学和适口性。 这里开发的这种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为临床的基本问题。

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.