Microneedle Delivery of Zanamivir for the Treatment of Influenza Infections
扎那米韦微针治疗流感感染
基本信息
- 批准号:10614045
- 负责人:
- 金额:$ 99.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-03-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdamantaneAddressAgreementCOVID-19 pandemicCessation of lifeCharacteristicsCirculationClinicalCommunitiesDataDevelopmentDevelopment PlansDevicesDiseaseDoseDrug KineticsDrynessEffectivenessElderlyEngineeringEnsureEpidemicEpitheliumFamily suidaeFormulationFutureHumanHydrogelsInfluenzaInfluenza preventionInhalationInhalation Drug AdministrationKineticsLightLiquid substanceLiteratureLungMarketingMedicalMethodsMiniature SwineModelingNeedlesNeuraminidase inhibitorOralOseltamivirPainPainlessPathogenicityPatientsPersonsPharmaceutical PreparationsPharmaceutical ServicesPharmacotherapyPhasePopulationPowder dose formPropertyPublishingPuncture procedureRattusRecommendationResearchResistanceRespiratory SystemRiskRouteSafetySeasonsSiteSkinSmall Business Innovation Research GrantSpecific qualifier valueSyringesSystemTherapeuticToxicologyTransdermal substance administrationVaccinationVaccinesVisitWorkabsorptionclinical developmenteconomic impacteffective therapyendonucleasefluimprovedinfluenza epidemicinfluenza infectioninfluenza outbreakinfluenza virus straininfluenzavirusinhibitormanufacturabilitymanufacturemortalitynovelnovel therapeuticspandemic diseasepatient populationpharmacokinetics and pharmacodynamicspre-Investigational New Drug meetingpreclinical studypreventproduct developmentprogramsprototyperesistant strainrespiratoryscale upseasonal influenzaskin barriertransmission processvaccine effectivenesszanamivir
项目摘要
Abstract
Yearly influenza epidemics strike millions of people, causing up to 500,000 deaths. Fatality caused by most
seasonal influenza viruses is <0.03%, but with significant mortality in the young and the elderly populations.
When a new pathogenic influenza strain enters the population, a pandemic could kill tens of millions of people
with a negative economic impact estimated to be over 150 billion dollars. Due to the incomplete efficacy of the
current vaccines, effective drug treatment is necessary. Presently, influenza treatment is only somewhat
effective, and some influenza strains are resistant to the currently marketed therapeutics, adamantanes and the
neuraminidase inhibitor Tamiflu®. However, while zanamivir (ZAN, Relenza®) remains highly active against
oseltamivir-resistant influenza strains, its therapeutic impact is severely limited by its route of administration, via
oral inhalation, which renders it unsuitable for patients with a compromised respiratory system. Therefore,
development of a novel delivery alternative for ZAN as we propose here, is poised to address a significant unmet
medical need.
Transdermal drug delivery offers a number of improvements over other delivery systems. The drug directly enters
the systemic circulation, circumventing absorption and first-pass barriers typical for oral delivery. It avoids skin
puncture by syringe needles, eliminating pain and patient visits to a clinician. Transdermal delivery of ZAN could
allow large numbers of patients to be reached during an influenza outbreak, which will be particularly important
in light of the added risk during the ongoing COVID-19 pandemic. While ZAN itself cannot cross the human skin
barrier at therapeutic rates, Microneedle (MN) - enhanced transdermal delivery is an elegant, efficient, and
painless method for increasing the skin permeation of many drugs, including ZAN. Our novel drug-device
combination product, TSR-066, consists of a swellable MN patch, which will continuously deliver ZAN over 5
days. This CRP proposal will support optimization and scale-up of the ZAN MN formulation and subsequent IND-
enabling toxicology studies in minipigs. We have obtained agreement with the FDA on the preclinical studies
needed in order to open the IND, as well as on the Phase I clinical development plans and the 505(b)2 regulatory
strategy. In addition to the experimental work proposed here, we will develop a robust IP expansion strategy for
the current ZAN MN product, as well as future product candidates that stand to benefit from MN-enabled delivery.
The end result of this work will be a novel, transdermal delivery approach for ZAN, which will expand its reach
into patient groups for which Relenza® is contraindicated and allow for simple administration for ZAN for both
treatment and prevention of the flu. We have assembled a team of expert advisors and collaborators to ensure
successful completion of this research plan.
摘要
每年流感流行袭击数百万人,造成多达50万人死亡。造成的死亡人数
季节性流感病毒的感染率<0.03%,但在年轻人和老年人中死亡率很高。
当一种新的致病性流感毒株进入人群时,大流行可能会导致数千万人死亡
负面经济影响估计超过1500亿美元。由于疗效不完全,
目前的疫苗,有效的药物治疗是必要的。目前,流感的治疗只是在一定程度上
有效,并且一些流感毒株对目前市售的治疗剂、金刚烷和
神经氨酸酶抑制剂Tamiflu®。然而,尽管扎那米韦(ZAN,Relenza®)对抗病毒药物仍然具有高度活性,
奥司他韦耐药流感病毒株,其治疗效果受到其给药途径的严重限制,
口服吸入,这使得它不适合呼吸系统受损的患者。因此,我们认为,
正如我们在这里提出的,开发一种新的ZAN交付替代品,有望解决一个重大的未满足的问题。
医疗需求。
经皮给药提供了许多优于其他给药系统的改进。药物直接进入
体循环、绕过口服递送的典型吸收和首过屏障。它避免皮肤
通过注射器针头穿刺,消除了疼痛和患者对临床医生的访问。ZAN的经皮递送可
在流感爆发期间能够接触到大量患者,这将特别重要
鉴于COVID-19疫情持续期间增加的风险。虽然ZAN本身无法穿过人体皮肤,
在治疗速率的屏障,微针(MN)增强的透皮给药是一种优雅,有效,
无痛的方法,增加皮肤渗透的许多药物,包括ZAN。我们的新型药物装置
组合产品TSR-066由可溶胀的MN贴片组成,其将持续提供超过5的ZAN
天该CRP提案将支持ZAN MN制剂和后续IND的优化和规模扩大。
使小型猪的毒理学研究成为可能。我们已与FDA就临床前研究达成一致
以及I期临床开发计划和505(B)2监管
战略除了这里提出的实验工作,我们将开发一个强大的IP扩展策略,
当前的ZAN MN产品,以及将从支持MN的交付中受益的未来候选产品。
这项工作的最终结果将是一种新的ZAN透皮给药方法,这将扩大其范围
用于禁忌使用Relenza®的患者组,并允许ZAN简单给药,
治疗和预防流感。我们组建了一个专家顾问和合作者团队,以确保
顺利完成了这项研究计划。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Elke Lipka其他文献
Elke Lipka的其他文献
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{{ truncateString('Elke Lipka', 18)}}的其他基金
Novel, Self-Applied MicroArray Patch (MAP) of Zanamivir for Treatment of the Flu
用于治疗流感的新型扎那米韦自用微阵列贴片 (MAP)
- 批准号:
10761086 - 财政年份:2023
- 资助金额:
$ 99.96万 - 项目类别:
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10546933 - 财政年份:2022
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Development of Synthetic High-Density Lipoproteins for Treatment of Sepsis
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Development of Synthetic High-Density Lipoproteins for Treatment of Sepsis
用于治疗脓毒症的合成高密度脂蛋白的开发
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10569516 - 财政年份:2022
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A Novel Combination Therapy to Treat Biofilm-based Pneumonia Infections
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9888308 - 财政年份:2019
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Development of MRS-2541, a methionyl-tRNA synthetase inhibitor, for Gram positive bacterial infections.
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- 批准号:
10699105 - 财政年份:2017
- 资助金额:
$ 99.96万 - 项目类别:
Microneedle Delivery of Zanamivir for Treatment of Influenza Infections
扎那米韦微针治疗流感感染
- 批准号:
9438857 - 财政年份:2017
- 资助金额:
$ 99.96万 - 项目类别:
Microneedle Delivery of Zanamivir for Treatment of Influenza
扎那米韦微针治疗流感
- 批准号:
10132966 - 财政年份:2017
- 资助金额:
$ 99.96万 - 项目类别:
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