Device for Acamprosate Transcutaneous Delivery to Reduce Alcohol Consumption.

描述(申请人提供)：酒精依赖是一种慢性疾病，有遗传、心理社会和环境方面的基础。酒精对社会的影响是广泛的；据估计，美国有1760万人滥用或依赖酒精。(Grant等人，2004年)。在美国，酒精依赖被认为是第三大可预防的死亡原因，仅次于吸烟和肥胖，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)。在过去的十年中，人们对使用药物疗法治疗酒精依赖的兴趣与日俱增(Swift，1999；Anton和Swift，2003)。阿卡米松/Campral(乙酰高牛尿酸钙)是一种FDA批准的新药，可促进酒精戒断，并有可能减少酒精依赖的影响。然而，氨基己酸酯的一个问题是其生物利用度很低，因为只有11%的口服剂量被吸收。此外，生物利用度低需要每天三次给药，这可以减少药物依从性，导致更少的药物剂量。提高氨基己酸酯的生物利用度可以改善其有效性。在乙醇自身给药的动物模型中，氨基己酸酯治疗已被证明可以减少乙醇的摄入量(Boismare等人，1984)，但不能减少食物或液体的摄入量(Chachowski等人，2001；Naassila等人，1998)，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。如果一种非肠道给药方法可以应用于人类，它可以显著提高氨基己酸酯的有效性。一个由学术界和工业界的专家组成的独特的跨学科团队将在第一阶段开发一种可穿戴、非侵入性的递送设备，在第一阶段具有较高的预期生物利用度。通过从加压储液器中释放受控数量的阿卡米松溶液，通过中空微针阵列非侵入性地通过皮肤角质层，阿卡米松将绕过皮肤屏障，通过皮肤毛细血管直接扩散到血液中。因此，经皮、血流调节、微针阵列增强的阿卡米松口服生物利用度有望增加5-7倍，因此在大鼠模型研究中，55%-80%的剂量被吸收。

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.