Device for Acamprosate Transcutaneous Delivery to Reduce Alcohol Consumption.

用于减少酒精消耗的阿坎酸经皮输送装置。

• 批准号: 7157433
• 负责人: ROBERT M SWIFT
• 金额: $ 15万
• 依托单位: TECHNOVA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-10 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157433
• 关键词: acamprosate; alcoholism /alcohol abuse chemotherapy; biological models; biomedical equipment development; drug delivery systems; laboratory rat; liquid chromatography mass spectrometry; miniature biomedical equipment; pharmacokinetics; polymers; slow release drug; topical drug application

DESCRIPTION (provided by applicant): Alcohol dependence is a chronic disorder with genetic, psychosocial, and environmental underpinnings. Alcohol's societal impact is widespread; it is estimated that there are 17.6 million individuals who abuse or depend on alcohol in the United States. (Grant et al, 2004). Alcohol dependence is considered the third leading preventable cause of death in the United States after cigarette smoking and obesity, attributing to more than 100,000 deaths per year. Overall, the annual economic cost of alcohol abuse, in the United States alone, exceeds $185 billion (Harwood, 2000). In the past decade, there has been increasing interest in the use of pharmacotherapies to treat alcohol dependence (Swift, 1999; Anton and Swift, 2003). Acamprosate/Campral (acetyl calcium homotaurinate) is a new, FDA-approved medication that promotes alcohol abstinence and can potentially reduce the impact of alcohol dependence. However, 1 of the problems with acamprosate is its poor bioavailability, as only 11% of an oral dose is absorbed. Moreover, the low bioavailability necessitates thrice daily dosing, which can reduce medication adherence and result in less medication dose. Improving acamprosate bioavailability can improve its effectiveness. In animal models of ethanol self-administration, acamprosate treatment has been shown to decrease ethanol intake (Boismare et al., 1984) but not food or fluid intake (Czachowski et al., 2001; Naassila et al., 1998) when administered parenterally which is the preferred method of administration for animal models, thus eliminating the problems with oral bioavailability and gastro-intestinal side effects. If a parenteral administration method could be applied to humans, it could significantly improve the effectiveness of acamprosate. A unique, interdisciplinary team of experts from academia and industry will develop a wearable, non-invasive delivery device, with a high expected bioavailability for acamprosate, during Phase 1. By releasing a controlled amount of solution of acamprosate from a pressurized reservoir, through the skin's stratum corneum, non-invasively via a hollow microneedle array, the acamprosate will bypass the skin barrier, and diffuse directly into the blood, via the skin capillaries. Thus, the transcutaneous, flow-modulated, microneedle array-enhanced delivery of acamprosate is expected to increase up to 5-7 times its poor (11%) oral bioavailability, so that 55-80% of a dose is absorbed in a rat-model study.

描述（由申请人提供）：酒精依赖是一种具有遗传、心理和环境基础的慢性疾病。酒精的社会影响是广泛的。据估计，美国有 1760 万人滥用或依赖酒精。 （格兰特等人，2004）。酒精依赖被认为是美国继吸烟和肥胖之后第三大可预防的死亡原因，每年导致超过 10 万人死亡。总体而言，仅在美国，每年因酗酒造成的经济损失就超过 1850 亿美元（Harwood，2000 年）。在过去的十年中，人们对使用药物疗法治疗酒精依赖越来越感兴趣（Swift，1999；Anton 和 Swift，2003）。 Acamprosate/Campral（乙酰基高牛磺酸钙）是 FDA 批准的一种新药物，可促进戒酒，并有可能减少酒精依赖的影响。然而，阿坎酸的问题之一是其生物利用度差，因为口服剂量仅 11% 被吸收。此外，低生物利用度需要每日三次给药，这会降低药物依从性并导致药物剂量减少。提高阿坎酸的生物利用度可以提高其有效性。在自我给药乙醇的动物模型中，阿坎酸治疗已被证明可以减少乙醇摄入量（Boismare等人，1984年），但肠胃外给药时不会减少食物或液体摄入量（Czachowski等人，2001年；Naassila等人，1998年）这是动物模型的首选给药方法，从而消除了口服生物利用度和胃肠道​​副作用的问题。如果肠胃外给药方法可以应用于人类，则可以显着提高阿坎酸的有效性。来自学术界和工业界的独特跨学科专家团队将在第一阶段开发一种可穿戴、非侵入性输送装置，该装置具有较高的阿坎酸预期生物利用度。通过空心微针阵列非侵入性地进入皮肤角质层，阿坎酸将绕过皮肤屏障，并通过皮肤毛细血管直接扩散到血液中。因此，经皮、流量调节、微针阵列增强的阿坎酸递送预计可增加至其较差的口服生物利用度（11%）的5-7倍，因此55-80%的剂量被大鼠吸收。模型研究。