Novel antiretroviral therapy delivery platform for infants and young children: oral dispensable strips (ODS)

项目摘要 130万至240万15岁以下儿童感染艾滋病毒，需要定期治疗。估计数 每年儿童中与艾滋病毒有关的死亡人数高达16万人，而且往往源于贫困患者 和照顾者的忠诚度。依从性差的原因根源于现有产品的适口性低 制剂(液体、速溶片)、制备和给药的复杂性以及 与患者隐私/社会污名相关的问题。Oak Treeutics，Inc.是一个早期阶段 一家制药公司，专门从事支撑体基质条的配方和制造 由口腔崩解聚合物(Ods)组成。这项提议的目标是开发可溶解的 支持多种药物儿科配方并首次商业化的条带(Ods)平台 阿巴卡韦/拉米夫定/多洛替格韦(ALD-1)的儿科抗病毒药物制剂 消耗臭氧层物质)。我们已经开发出含有两种艾滋病毒儿科预防性剂量的消耗臭氧层物质。 适合婴幼儿服用的抗逆转录病毒药物(AZT和NVP) 儿童，包括粘液粘连、快速口腔分散和口感遮盖。在本提案中，我们将 开发一种新的多药物消耗臭氧层物质配方的计算方法，该方法将用于 封装并制成ALD-ODS条带。最佳消耗臭氧层物质候选者将与商业广告进行比较 在活体PK/PD研究中确定药物动力学的治疗和分析的参考标准 和毒物学特征。最终的ald-ods产品将是第一个含有HIV组合的口腔药膜 军团药物。它也将是第一个达到口服溶解的目标标准的 产品，它将是首批包含所有推荐一线药物的儿科产品之一 单一配方，易于修改剂量，简化护理人员的管理。

PROJECT ABSTRACT Between 1.3 – 2.4 million children under 15 live with HIV and are in need of regular treatment. Estimates for HIV related deaths among children are as high as 160,00 annually and often rooted in poor patient and caregiver adherence. Causes for poor adherence are rooted in low palatability of existing formulations (liquids, fast-dissolving tablets), the complexity of preparation and administration, and issues related to patient privacy / social stigma. Oak Therapeutics, Inc., is an early-stage pharmaceutical company that specializes in formulation and manufacturing of support matrix strips composed of oral-disintegrating polymers (ODS). The goal of this proposal is to develop dissolvable strip (ODS) platform that supports multi-drug pediatric formulation and to commercialize the first ever ODS formulation for pediatric antiviral therapy consisting of Abacavir/ Lamivudine/ Dolutegravir (ALD- ODS). We have already developed ODS containing a pediatric prophylactic dose of two HIV antiretroviral drugs (AZT and NVP) with appropriate properties for administration to infants and young children, including muco-adhesion, rapid oral dispersion, and taste-masking. In this proposal we will develop a novel computational method for multi- drug ODS formulation which will be used to encapsulate and make ALD-ODS strip. Optimal ODS candidate will be compared to commercial reference standard of treatment and analyzed in an in vivo PK/PD study to determine pharmacokinetics and toxicology profiles. The final ALD-ODS product will be the first oral film to contain HIV combination regiment medications. It will also be the first to achieve the targeted criteria of an orally dissolvable product, and it will be among the first pediatric products to contain all recommended first line drugs in a single formulation with easily modified dosing to simplify administration for caregivers.