Expansion of Engineering and Testing for 'Locally Targeted Acoustic Neuropathy Medication Delivery System for Pain Relief without Large Systemic Doses and Side Effects'

扩大“用于缓解疼痛且无大全身剂量和副作用的局部靶向听神经病药物输送系统”的工程和测试

• 批准号: 9933278
• 负责人: Maureen L. Mulvihill
• 金额: $ 2.41万
• 依托单位: ACTUATED MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2020-12-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9933278
• 关键词: Absence of pain sensation; Acoustics; Acute Pain; Affect; Age; American; Analgesics; Area; Bypass; Charge; Clinical; Clinical Research; Clinical Trials; Cosmetics; Cyclic GMP; Devices; Disease; Dose; Drug Delivery Systems; Effectiveness; Electrodes; Engineering; Ensure; Family suidae; Frequencies; Goals; Health; Health Care Costs; Home environment; Human; Hybrids; Hyperalgesia; In Vitro; Injections; Injury; Iontophoresis; Knowledge; Lesion; Lidocaine; Manufacturer Name; Measurement; Measures; Medical; Medical Device; Medical center; Methods; Modeling; Moods; Motion; Needles; Nerve; Nervous system structure; Neuropathy; Numbness; Oral; Outcome; Pain; Pain management; Painless; Patients; Peripheral; Peripheral Nervous System; Peripheral Nervous System Diseases; Permeability; Persons; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Phase; Preclinical Testing; Prevalence; Public Health; Quality of life; Safety; Sales; Secure; Series; Site; Skin; Skin Tissue; Sleep; Small Business Innovation Research Grant; Stimulus; Stratification; Symptoms; System; Technology; Testing; Thick; Tissues; Topical application; Ultrasonic Transducer; Ultrasonography; Universities; Work; addiction; allodynia; base; clinically relevant; dalton; disabling symptom; dosage; effective therapy; electric field; electric impedance; gabapentin; gastrointestinal; human very old age (85+); improved; innovation; interest; molecular size; operation; pain relief; pain sensation; peripheral pain; preclinical study; preclinical trial; programs; research clinical testing; side effect; social; somatosensory; tool; uptake; verification and validation; virtual; voltage; wasting

This Phase I SBIR develops the Locally Targeted Acoustic (LTA) Neuropathy Medication Delivery System to effectively provide localized analgesia via direct transdermal delivery of medications to target nerves – improving efficacy and eliminating both wasted/discarded drug and the negative side effects associated with oral/systemic delivery. Public Health Problem: Peripheral Neuropathy (PN) is a series of disorders resulting from damage to the peripheral somatosensory nervous system resulting from lesion, injury, or disease. Debilitating symptoms of PN include numbness, tingling, and/or pain sensations such as allodynia (a normally non-painful stimulus causing pain) or hyperalgesia (an increased sensitivity to normally painful stimuli). PN can significantly affect quality of life. It is estimated that 1 in 15 Americans (i.e., 20.8M of 312M) suffer from PN. Currently, the most effective treatment of PN is pharmacological therapy. However, only 40-60% of patients achieve clinically meaningful relief, partially due to various types of neuropathy not being affected by ordinary analgesics. Many treatments cause debilitating side-effects due to their administration method (e.g., gastrointestinal) or the high levels of systemic uptake required to achieve effect. Alternative localized drug therapies do exist, but many have drawbacks to their administration methods. Needle injections cause acute pain, while topically-applied pain medications are limited by their molecular size since skin is virtually impermeable to molecules larger than 500 Daltons. A device is needed that can deliver PN medications to targeted areas through the skin, quickly and efficiently - regardless of molecular size. Hypothesis. LTA demonstrates feasibility of a hybrid US/iontophoresis topical PN treatment to efficiently deliver clinically-relevant dosages of gabapentin from 1% solution into porcine skin in vitro, leading to pre-clinical and clinical testing in Phase II. Aim 1 – LTA US component permeabilizes skin ≤5 minutes, and iontophoresis component accurately predicts skin permeabilization in vitro via secondary use as skin impedance measurement tool. Aim 2 – Fifteen-minute operation of LTA in dual-mode delivers >25% of gabapentin dose into full- thickness porcine skin in vitro.

第一阶段SBIR开发了局部靶向听觉（LTA）神经病药物 通过直接经皮递送有效提供局部镇痛的递送系统 针对神经的药物-提高疗效并消除浪费/丢弃的药物 以及与口服/全身递送相关的负面副作用。 公共卫生问题：周围神经病（PN）是一系列由以下原因引起的疾病： 由病变、损伤或 疾病PN的衰弱症状包括麻木、刺痛和/或疼痛感 例如异常性疼痛（通常引起疼痛的非疼痛刺激）或痛觉过敏（例如 增加对正常疼痛刺激的敏感性）。PN可显著影响生活质量。是 据估计，每15个美国人中就有1个（即，3.12亿人中的20.8亿人患有PN。目前，最 PN的有效治疗是药物治疗。只有40-60%的患者 达到临床上有意义的缓解，部分原因是各种类型的神经病变没有被 受普通止痛药的影响。许多治疗方法由于它们的副作用而导致衰弱。 给药方法（例如，胃肠道）或全身吸收所需的高水平， 达到效果。替代的局部药物疗法确实存在，但许多都有缺点， 他们的管理方法。针头注射引起急性疼痛，而局部应用的疼痛 药物受到其分子大小的限制，因为皮肤实际上是不可渗透的， 分子量大于500道尔顿。需要一种能够将PN药物输送至 通过皮肤的目标区域，快速，有效-无论分子大小。 假说. LTA证明了混合US/离子电渗局部PN治疗的可行性， 有效地将临床相关剂量的加巴喷丁从1%溶液递送到猪皮肤中 在体外，导致临床前和临床试验在第二阶段。目标1 -长期协议美国部分 渗透皮肤≤5分钟，离子电渗成分准确预测皮肤 通过二次使用作为皮肤阻抗测量工具进行体外透化。目标2 - LTA在双模式下的15分钟操作将>25%的加巴喷丁剂量输送到全 厚猪皮。