Development of a Dissolving Film for Allergen Immunotherapy in Children

开发用于儿童过敏原免疫治疗的溶解膜

基本信息

批准号：
8510886
负责人：
Corinne Keet
金额：
$ 25.14万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-10 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8510886
关键词：
Absenteeism Address Admission activity Adult Affect Allergen Immunotherapy Allergens Allergic Disease Allergic rhinitis Allergy to peanuts Antigen-Presenting Cells Area Asthma Biomedical Engineering Characteristics Child Childhood Childhood Asthma Chronic Disease Clinic Clinical Trials Collaborations Core Facility Deglutition Developing Countries Development Dictyoptera Disease Dose Drug Delivery Systems Drug Formulations Drug Kinetics Effector Cell Emergency Situation Ensure Europe Excipients Extrinsic asthma FDA approved Face Felis catus Film Food Food Hypersensitivity Goals Grant Hospitals Hypersensitivity Immunology Immunotherapy In Situ Inhalant dose form Injection of therapeutic agent Learning Liquid substance Location Methodology Methods Milk Hypersensitivity Modeling Morbidity - disease rate Oral Oral cavity Oral mucous membrane structure Peanuts - dietary Pharmacy (field)Phase Powder dose form Process Property Research Risk Safety Schools Time Tongue Translating Translations Vaccination Visit design experience flexibility improved liquid formulation novel oral immunotherapy pediatrician prevent public health relevance respiratory sublingual immunotherapy

项目摘要

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.

描述（由申请人提供）：过敏性疾病是儿童时期最常见的慢性疾病，并导致显着的发病率。然而，过敏原特异性注射免疫疗法对于许多儿童来说是不可接受的，并且对于某些类型的过敏可能风险太大，但它仍然是唯一被批准的过敏性疾病疾病缓解疗法。舌下免疫疗法已被证明对于治疗食物和空气过敏更安全，但目前的方法并未在功效、安全性或实用性方面进行优化，并且未获批准在美国使用。粘膜粘附溶解膜改进了目前的液体治疗方法。免疫疗法，因为它（1）延长抗原呈递细胞和过敏原之间的接触，这对于免疫疗法的功效至关重要，（2）允许更灵活的剂量，更高和更低的标准化剂量比目前可用的方法，（3）对于儿童来说是一种更实用的方法，几乎不需要合作，（4）与液体不同，不受误吸的风险。我们开发了这样一种薄膜用于治疗花生过敏。在这笔赠款中，我们建议将该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。目标 1 是开发和完善用于治疗蟑螂和猫过敏的口腔溶解条。这些过敏是导致儿童过敏性鼻炎和哮喘的两个最重要的因素，每种过敏都为电影设计带来了独特的挑战和机遇。目标 2 是通过评估口腔中不同位置的影响以及配方（如果需要）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向临床转化的基本问题。